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Fabrizio DI BENEDETTO

Professore Ordinario
Dipartimento Chirurgico, Medico, Odontoiatrico e di Scienze Morfologiche con interesse Trapiantologico, Oncologico e di Medicina Rigenerativa

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Pubblicazioni

2023 - Adherence to Mediterranean diet in liver transplant recipients: a cross-sectional multicenter study [Articolo su rivista]
Gitto, Stefano; Golfieri, Lucia; Sofi, Francesco; Tamè, Maria R; Vitale, Giovanni; DE Maria, Nicola; Marzi, Luca; Mega, Andrea; Valente, Giovanna; Borghi, Alberto; Forte, Paolo; Cescon, Matteo; DI Benedetto, Fabrizio; Andreone, Pietro; Petranelli, Marco; Dinu, Monica; Carrai, Paola; Arcangeli, Giulio; Grandi, Silvana; Lau, Chloe; Morelli, Maria Cristina; DE Simone, Paolo; Chiesi, Francesca; Marra, Fabio
abstract

Background: Seeing the importance of healthy diet after liver transplant (LT), our study aimed to evaluate the adherence to Mediterranean diet (MD) in a large population of LT recipients. Methods: The present multicenter study was developed in clinically stable, liver transplanted patients, from June to September 2021. Patients completed a survey about adherence to MD, Quality of Life (QoL), sport, and employment. To analyze the correlations, we computed Pearson's coefficients; while to compare subgroups, independent samples t-tests and ANOVAs. We used a multivariable logistic regression analysis to find the predictors of impaired adherence to MD. Results: The questionnaire was administered to 511 patients. They were males in 71% of cases with a mean age of 63.1 years (SD±10.8). LT recipients coming from central Italy displayed higher adherence to the MD (M=11.10±1.91) than patients from northern (M=9.94±2.28, P<0.001) or southern Italy (M=10.04±2.16, P<0.001). Patients from central Italy showed a significantly higher consumption of fruit, vegetables, legumes, cereals, olive oil, fish and a significantly lower intake of dairy products than patients resident in the other Italian areas. At multivariate analysis, recipients from central Italy were 3.8 times more likely to report adherence to the MD. Patients with a high physical health score were more adherent to MD, as well as patients transplanted at an earlier time. Conclusions: We demonstrated that place of stay, time from transplant and physical dimension of QoL significantly influences the adherence to MD. Continuous information campaigns about a correct diet and lifestyle would be necessary.

2023 - ASO Author Reflections: Robotic Perihilar Cholangiocarcinoma Beyond Technical Feasibility [Articolo su rivista]
Di Benedetto, F; Magistri, P; Di Sandro, S
abstract

2023 - Comparison between the difficulty of laparoscopic limited liver resections of tumors located in segment 7 versus segment 8: An international multicenter propensity-score matched study [Articolo su rivista]
Efanov, M.; Salimgereeva, D.; Alikhanov, R.; Wu, A. G. R.; Geller, D.; Cipriani, F.; Aghayan, D. L.; Fretland, A. A.; Sijberden, J.; Belli, A.; Marino, M. V.; Mazzaferro, V.; Chiow, A. K. H.; Sucandy, I.; Ivanecz, A.; Choi, S. H.; Lee, J. H.; Prieto, M.; Vivarelli, M.; Giuliante, F.; Ruzzenente, A.; Yong, C. -C.; Fondevila, C.; Rotellar, F.; Choi, G. -H.; Robless Campos, R.; Wang, X.; Sutcliffe, R. P.; Pratschke, J.; Lai, E.; Chong, C. C.; D'Hondt, M.; Monden, K.; Lopez-Ben, S.; Herman, P.; Di Benedetto, F.; Kingham, T. P.; Liu, R.; Long, T. C. D.; Ferrero, A.; Levi Sandri, G. B.; Cherqui, D.; Scatton, O.; Wakabayashi, G.; Troisi, R. I.; Cheung, T. -T.; Sugioka, A.; Han, H. -S.; Abu Hilal, M.; Soubrane, O.; Fuks, D.; Aldrighetti, L.; Edwin, B.; Goh, B. K. P.; Chan, C. -Y.; Syn, N.; D'Silva, M.; Lee, B.; Lim, C.; Nghia, P. P.; Gastaca, M.; Schotte, H.; De Meyere, C.; Krenzien, F.; Schmelzle, M.; Lee, K. -F.; Lee, L. S.; Jang, J. Y.; Kojima, M.; Kato, Y.; Ghotbi, J.; Kruger, J. A. P.; Coelho, F. F.; Lopez-Lopez, V.; Valle, B. D.; Robert, M. C. I.; Mishima, K.; Montalti, R.; Giglio, M.; Wang, H. -P.; Pascual, F.; Saleh, M.; Kadam, P.; Tang, C. -N.; Ardito, F.; Vani, S.; Giustizieri, U.; Citterio, D.; Mocchegiani, F.; Ettorre, G. M.; Colasanti, M.; Guzman, Y.; Dogeas, E.; Magistri, P.; Mazzotta, A.
abstract

Background: Presently, according to different difficulty scoring systems, there is no difference in complexity estimation of laparoscopic liver resection (LLR) of segments 7 and 8. However, there is no published data supporting this assumption. To date, no studies have compared the outcomes of laparoscopic parenchyma-sparing resection of the liver segments 7 and 8. Methods: A post hoc analysis of patients undergoing LLR of segments 7 and 8 in 46 centers between 2004 and 2020 was performed. 1:1 Propensity score matching (PSM) was used to compare isolated LLR of segments 7 and 8. Subset analyses were also performed to compare atypical resections and segmentectomies of 7 and 8. Results: A total of 2411 patients were identified, and 1691 patients met the inclusion criteria. Comparison after PSM between the entire cohort of segment 7 and segment 8 resections revealed inferior results for segment 7 resection in terms of increased blood loss, blood transfusions, and conversions to open surgery. Subset analyses of only atypical resections similarly demonstrated poorer outcomes for segment 7 in terms of increased blood loss, operation time, blood transfusions, and conversions to open surgery. Conversely, a subgroup analysis of segmentectomies after PSM found better outcomes for segment 7 in terms of a shorter operation time and hospital stay. Conclusion: Differences in the outcomes of segments 7 and 8 resections suggest a greater difficulty of laparoscopic atypical resection of segment 7 compared to segment 8, and greater difficulty of segmentectomy 8 compared to segmentectomy 7.

2023 - Death After Liver Transplantation: Mining Interpretable Risk Factors for Survival Prediction [Relazione in Atti di Convegno]
Guidetti, V.; Dolci, G.; Franceschini, E.; Bacca, E.; Burastero, G. J.; Ferrari, D.; Serra, V.; Di Benedetto, F.; Mussini, C.; Mandreoli, F.
abstract

This study introduces a novel approach to mine risk factors for short-term death after liver transplantation (LT). The method outputs intelligible survival models by combining Cox's regression with a genetic programming technique known as multi-objective symbolic regression (MOSR). We consider 485 Electronic Health Records (EHRs) of patients who underwent LT, containing information on hospitalization and preoperative conditions, with a focus on infections and colonizations by multi-resistant Gram-negative bacteria. We evaluate MOSR outcomes against several performance metrics and demonstrate that they are well-calibrated, predictive, safe, and parsimonious. Finally, we select the most promising post-LT early survival risk score based on information criteria, performance, and out-of-distribution safety. Validating this technique at a multicenter level could improve service pipeline logistics through a trustworthy machine-learning method.

2023 - Feasibility, safety, and outcome of second-line nivolumab/bevacizumab in liver transplant patients with recurrent hepatocellular carcinoma [Articolo su rivista]
Di Marco, Lorenza; Pivetti, Alessandra; Foschi, Francesco Giuseppe; D'Amico, Roberto; Schepis, Filippo; Caporali, Cristian; Casari, Federico; Lasagni, Simone; Critelli, Rosina Maria; Milosa, Fabiola; Romanzi, Adriana; Marcelli, Gemma; De Maria, Nicola; Romagnoli, Dante; Catellani, Barbara; Scianò, Filippo; Magistri, Paolo; Colecchia, Antonio; Sighinolfi, Pamela; Di Benedetto, Fabrizio; Martinez-Chantar, Maria-Luz; Villa, Erica
abstract

2023 - From Listing to Recovery: A Review of Nutritional Status Assessment and Management in Liver Transplant Patients [Articolo su rivista]
Ravaioli, F.; De Maria, N.; Di Marco, L.; Pivetti, A.; Casciola, R.; Ceraso, C.; Frassanito, G.; Pambianco, M.; Pecchini, M.; Sicuro, C.; Leoni, L.; Di Sandro, S.; Magistri, P.; Menozzi, R.; Di Benedetto, F.; Colecchia, A.
abstract

Liver transplantation (LT) is a complex surgical procedure requiring thorough pre- and post-operative planning and care. The nutritional status of the patient before, during, and after LT is crucial to surgical success and long-term prognosis. This review aims to assess nutritional status assessment and management before, during, and after LT, with a focus on patients who have undergone bariatric surgery. We performed a comprehensive topic search on MEDLINE, Ovid, In-Process, Cochrane Library, EMBASE, and PubMed up to March 2023. It identifies key factors influencing the nutritional status of liver transplant patients, such as pre-existing malnutrition, the type and severity of liver disease, comorbidities, and immunosuppressive medications. The review highlights the importance of pre-operative nutritional assessment and intervention, close nutritional status monitoring, individualised nutrition care plans, and ongoing nutritional support and monitoring after LT. The review concludes by examining the effect of bariatric surgery on the nutritional status of liver transplant recipients. The review offers valuable insights into the challenges and opportunities for optimising nutritional status before, during, and after LT.

2023 - Liver transplantation for iatrogenic injuries secondary to cholecystectomy: a systematic review [Articolo su rivista]
Guidetti, C.; Pang, N. Q.; Catellani, B.; Magistri, P.; Caracciolo, D.; Guerrini, G. P.; Pecchi, A.; Di Sandro, S.; Di Benedetto, F.
abstract

INTRODUCTION: Iatrogenic injury to the liver hilum during cholecystectomy is a severe surgical complication, with liver transplantation (LT) as the final drastic solution. The authors report the experience of our center and conduct a review of the literature on the outcomes of LT performed in this setting. METHODS: Data sources included MEDLINE, EMBASE, and CENTRAL from inception to 19 June 2022. Studies reporting on patients treated with LT for liver hilar injuries following cholecystectomy were included. Incidence, clinical outcomes, and survival data were synthesized through a narrative review. RESULTS: Twenty-seven articles were identified, including 213 patients. Eleven (40.7%) articles highlighted deaths within 90-days post-LT. Post-LT mortality was reported in 28 (13.1%) patients. Severe complications (≥Clavien III) occurred in at least 25.8% ( n =55) of patients. Within larger cohorts, 1-year overall survival (OS) was 76.5-84.3%, and 5-year OS was 67.2-83.0%. The authors also highlight our own experience managing 14 patients with liver hilar injury secondary to cholecystectomy, of which two required LT. CONCLUSION: While short-term morbidity and mortality is significant, available long-term data suggests reasonable OS in these patients following LT. Future studies are necessary to better understand the relationship between different types of liver hilar injury, transplant indication, and outcomes of LT in this setting.

2023 - Mortality after transjugular intrahepatic portosystemic shunt in older adult patients with cirrhosis: A validated prediction model [Articolo su rivista]
Vizzutti, F.; Celsa, C.; Calvaruso, V.; Enea, M.; Battaglia, S.; Turco, L.; Senzolo, M.; Nardelli, S.; Miraglia, R.; Roccarina, D.; Campani, C.; Saltini, D.; Caporali, C.; Indulti, F.; Gitto, S.; Zanetto, A.; Di Maria, G.; Bianchini, M.; Pecchini, M.; Aspite, S.; Di Bonaventura, C.; Citone, M.; Guasconi, T.; Di Benedetto, F.; Arena, U.; Fanelli, F.; Maruzzelli, L.; Riggio, O.; Burra, P.; Colecchia, A.; Villa, E.; Marra, F.; Camma, C.; Schepis, F.
abstract

Background and Aims: Implantation of a transjugular intrahepatic portosystemic shunt (TIPS) improves survival in patients with cirrhosis with refractory ascites and portal hypertensive bleeding. However, the indication for TIPS in older adult patients (greater than or equal to 70 years) is debated, and a specific prediction model developed in this particular setting is lacking. The aim of this study was to develop and validate a multivariable model for an accurate prediction of mortality in older adults. Approach and Results: We prospectively enrolled 411 consecutive patients observed at four referral centers with de novo TIPS implantation for refractory ascites or secondary prophylaxis of variceal bleeding (derivation cohort) and an external cohort of 415 patients with similar indications for TIPS (validation cohort). Older adult patients in the two cohorts were 99 and 76, respectively. A cause-specific Cox competing risks model was used to predict liver-related mortality, with orthotopic liver transplant and death for extrahepatic causes as competing events. Age, alcoholic etiology, creatinine levels, and international normalized ratio in the overall cohort, and creatinine and sodium levels in older adults were independent risk factors for liver-related death by multivariable analysis. Conclusions: After TIPS implantation, mortality is increased by aging, but TIPS placement should not be precluded in patients older than 70 years. In older adults, creatinine and sodium levels are useful predictors for decision making. Further efforts to update the prediction model with larger sample size are warranted.

2023 - Pneumocystis jirovecii pneumonia in patients with decompensated cirrhosis: a case series [Articolo su rivista]
Franceschini, Erica; Dolci, Giovanni; Santoro, Antonella; Meschiari, Marianna; Riccò, Alice; Menozzi, Marianna; Burastero, Giulia Jole; Cuffari, Biagio; De Maria, Nicola; Serio, Lucia; Biagioni, Emanuela; Catellani, Barbara; Sandro, Stefano Di; Colecchia, Antonio; Girardis, Massimo; Benedetto, Fabrizio Di; Mussini, Cristina
abstract

Objectives: Pneumocystis jirovecii pneumonia (PCP) incidence is increasing in people without HIV. Decompensated liver cirrhosis is not currently considered a risk factor for PCP. The aim of this paper is to describe a case series of patients with decompensated liver cirrhosis and PCP. Methods: All consecutive patients hospitalized with decompensated cirrhosis and microbiology-confirmed PCP at Policlinico Modena University Hospital from January 1, 2016 to December 31, 2021 were included in our series. Results: Eight patients were included. All patients had advanced-stage liver disease with a model for end-stage liver disease score above 15 (6/8 above 20). Four were on an active orthotopic liver transplant waiting list at the time of PCP diagnosis. Five patients did not have any traditional risk factor for PCP, whereas the other three were on glucocorticoid treatment for acute-on-chronic liver failure. All patients were treated with cotrimoxazole, except two who died before the diagnosis. Five patients died (62.5%), four of them within 30 days from PCP diagnosis. Of the remaining three, one patient underwent liver transplantation. Conclusion: Although further studies are needed, liver cirrhosis can be an independent risk factor for PCP in patients with decompensated cirrhosis that is mainly due to severe alcoholic hepatitis and who are on corticosteroids therapy, and primary prophylaxis for PCP should be considered.

2023 - Successful living donor liver transplantation from an HIV and HCV positive donor: report from the first case in the world [Articolo su rivista]
Di Sandro, Stefano; Catellani, Barbara; Guidetti, Cristiano; Magistri, Paolo; Ballarin, Roberto; Pecchi, Annarita; Caracciolo, Daniela; Guaraldi, Giovanni; Guerrini, Gian Piero; Di Benedetto, Fabrizio
abstract

: HIV (human-immunodeficiency-virus) and HCV (hepatitis-C-virus) infections cause millions of deaths across the world every year. Since the introduction of effective therapies for HIV, in the middle of 1990 s, and HCV, after 2013, those two untreatable infections became completely controlled. Donor safety is the main goal in living donor liver transplantation (LDLT). An accurate pre-donation screening is mandatory for excluding risk factors related with any increase of donors' short-term and long-term morbidity. We present the first LDLT from a donor with both HIV and HCV previous infections. Donor and recipient did not experience any complication. Individuals with well controlled HIV/HCV infections and without any risk factors may be suitable for donation of a part of their healthy liver. An infographic is available for this article at:http://links.lww.com/QAD/C833.

2023 - The Italian data on SARS-CoV-2 infection in transplanted patients support an organ specific immune response in liver recipients [Articolo su rivista]
Rendina, M.; Barone, M.; Lillo, C.; Trapani, S.; Masiero, L.; Trerotoli, P.; Puoti, F.; Lupo, L. G.; Tandoi, F.; Agnes, S.; Grieco, A.; Andorno, E.; Marenco, S.; Giannini, E. G.; Baccarani, U.; Toniutto, P.; Carraro, A.; Colecchia, A.; Cescon, M.; Morelli, M. C.; Cillo, U.; Burra, P.; Angeli, P.; Colledan, M.; Fagiuoli, S.; De Carlis, L.; Belli, L.; De Simone, P.; Carrai, P.; Di Benedetto, F.; De Maria, N.; Ettorre, G. M.; Giannelli, V.; Gruttadauria, S.; Volpes, R.; Corsale, S.; Mazzaferro, V.; Bhoori, S.; Romagnoli, R.; Martini, S.; Rossi, G.; Caccamo, L.; Donato, M. F.; Rossi, M.; Ginanni Corradini, S.; Spada, M.; Maggiore, G.; Tisone, G.; Lenci, I.; Vennarecci, G.; Tortora, R.; Vivarelli, M.; Svegliati Baroni, G.; Zamboni, F.; Mameli, L.; Tafuri, S.; Simone, S.; Gesualdo, L.; Cardillo, M.; Di Leo, A.
abstract

Introduction: The study of immune response to SARSCoV-2 infection in different solid organ transplant settings represents an opportunity for clarifying the interplay between SARS-CoV-2 and the immune system. In our nationwide registry study from Italy, we specifically evaluated, during the first wave pandemic, i.e., in non-vaccinated patients, COVID-19 prevalence of infection, mortality, and lethality in liver transplant recipients (LTRs), using non-liver solid transplant recipients (NL-SOTRs) and the Italian general population (GP) as comparators. Methods: Case collection started from February 21 to June 22, 2020, using the data from the National Institute of Health and National Transplant Center, whereas the data analysis was performed on September 30, 2020.To compare the sex- and age-adjusted distribution of infection, mortality, and lethality in LTRs, NL-SOTRs, and Italian GP we applied an indirect standardization method to determine the standardized rate. Results: Among the 43,983 Italian SOTRs with a functioning graft, LTRs accounted for 14,168 patients, of whom 89 were SARS-CoV-2 infected. In the 29,815 NL-SOTRs, 361 cases of SARS-CoV-2 infection were observed. The geographical distribution of the disease was highly variable across the different Italian regions. The standardized rate of infection, mortality, and lethality rates in LTRs resulted lower compared to NL-SOTRs [1.02 (95%CI 0.81-1.23) vs. 2.01 (95%CI 1.8-2.2); 1.0 (95%CI 0.5-1.5) vs. 4.5 (95%CI 3.6-5.3); 1.6 (95%CI 0.7-2.4) vs. 2.8 (95%CI 2.2-3.3), respectively] and comparable to the Italian GP. Discussion: According to the most recent studies on SOTRs and SARS-CoV-2 infection, our data strongly suggest that, in contrast to what was observed in NL-SOTRs receiving a similar immunosuppressive therapy, LTRs have the same risk of SARS-CoV-2 infection, mortality, and lethality observed in the general population. These results suggest an immune response to SARS-CoV-2 infection in LTRS that is different from NL-SOTRs, probably related to the ability of the grafted liver to induce immunotolerance.

2022 - A comparison of three classification systems for stillbirth [Articolo su rivista]
DI BENEDETTO, Fabrizio; Fabio, F.; Francesca, M.; Gaia, P.
abstract

Background: Understanding the causes of perinatal death can provide relevant information to couples, caregivers, and society. Classification systems play a crucial role in identifying the most relevant conditions suggesting preventive measures for decreasing stillbirth (SB). In 2016 the International Classification of Disease to Deaths during the Perinatal Period (ICD-PM) was released with the aim to suggest a universally accepted classification. Methods: This is a prospective cohort study that enrolled all SBs occurred in Emilia–Romagna, from 2014 to 2017. We prospectively applied ReCoDe classification and retrospectively used Simplified CODAC classification and ICD-PM. The aim of this study is to compare different classification systems on a cohort of SBs, undergoing a comprehensive workup, to establish what classification minimizes rates of unexplained SB. Results: We registered 443 SBs. According to ReCoDe the largest category of SB was “placental insufficiency/infarction” (16.9%), followed by “abruptio placentae” (14.2%). Unexplained cases are 16.7%. Gestational age <37 weeks is less frequent in the group of women with unclassified SB (OR 0.50, OR95%CI [0.3–0.8]) against women with classified SB. Considering CODAC the two largest categories are “infarctions or thrombi” (16.3%) and “abruption or retro-placental haematoma” (15.1%), instead only 17.2% of cases remained unexplained. Conclusions: Comparing ReCoDe and CODAC we found no real difference in any category. ReCoDe and CODAC better underlines the primary cause of death. ICD-PM reveals to be easily applicable to clinical practice. ICD-PM has the lowest rate of unexplained SBs (9.3%) due to the structure itself and not to a deeper comprehension of death.

2022 - A multicentre outcome analysis to define global benchmarks for donation after circulatory death liver transplantation [Articolo su rivista]
Schlegel, A.; van Reeven, M.; Croome, K.; Parente, A.; Dolcet, A.; Widmer, J.; Meurisse, N.; De Carlis, R.; Hessheimer, A.; Jochmans, I.; Mueller, M.; van Leeuwen, O. B.; Nair, A.; Tomiyama, K.; Sherif, A.; Elsharif, M.; Kron, P.; van der Helm, D.; Borja-Cacho, D.; Bohorquez, H.; Germanova, D.; Dondossola, D.; Olivieri, T.; Camagni, S.; Gorgen, A.; Patrono, D.; Cescon, M.; Croome, S.; Panconesi, R.; Carvalho, M. F.; Ravaioli, M.; Caicedo, J. C.; Loss, G.; Lucidi, V.; Sapisochin, G.; Romagnoli, R.; Jassem, W.; Colledan, M.; De Carlis, L.; Rossi, G.; Di Benedetto, F.; Miller, C. M.; van Hoek, B.; Attia, M.; Lodge, P.; Hernandez-Alejandro, R.; Detry, O.; Quintini, C.; Oniscu, G. C.; Fondevila, C.; Malago, M.; Pirenne, J.; Ijzermans, J. N. M.; Porte, R. J.; Dutkowski, P.; Taner, C. B.; Heaton, N.; Clavien, P. -A.; Polak, W. G.; Muiesan, P.; Alwayn, I. P. J.; van der Berg, A. P.; Carbonaro, M.; Claasen, M.; Daud, A.; de Meijer, V. E.; Metselaar, H. J.; Monbaliu, D.; Paolucci, M.; Vets, S.; Winter, E.
abstract

Background & Aims: The concept of benchmarking is established in the field of transplant surgery; however, benchmark values for donation after circulatory death (DCD) liver transplantation are not available. Thus, we aimed to identify the best possible outcomes in DCD liver transplantation and to propose outcome reference values. Methods: Based on 2,219 controlled DCD liver transplantations, collected from 17 centres in North America and Europe, we identified 1,012 low-risk, primary, adult liver transplantations with a laboratory MELD score of ≤20 points, receiving a DCD liver with a total donor warm ischemia time of ≤30 minutes and asystolic donor warm ischemia time of ≤15 minutes. Clinically relevant outcomes were selected and complications were reported according to the Clavien-Dindo-Grading and the comprehensive complication index (CCI). Corresponding benchmark cut-offs were based on median values of each centre, where the 75th-percentile was considered. Results: Benchmark cases represented between 19.7% and 75% of DCD transplantations in participating centres. The 1-year retransplant and mortality rates were 4.5% and 8.4% in the benchmark group, respectively. Within the first year of follow-up, 51.1% of recipients developed at least 1 major complication (≥Clavien-Dindo-Grade III). Benchmark cut-offs were ≤3 days and ≤16 days for ICU and hospital stay, ≤66% for severe recipient complications (≥Grade III), ≤16.8% for ischemic cholangiopathy, and ≤38.9 CCI points 1 year after transplant. Comparisons with higher risk groups showed more complications and impaired graft survival outside the benchmark cut-offs. Organ perfusion techniques reduced the complications to values below benchmark cut-offs, despite higher graft risk. Conclusions: Despite excellent 1-year survival, morbidity in benchmark cases remains high. Benchmark cut-offs targeting morbidity parameters offer a valid tool to assess the protective value of new preservation technologies in higher risk groups and to provide a valid comparator cohort for future clinical trials. Lay summary: The best possible outcomes after liver transplantation of grafts donated after circulatory death (DCD) were defined using the concept of benchmarking. These were based on 2,219 liver transplantations following controlled DCD donation in 17 centres worldwide. Donor and recipient combinations with higher risk had significantly worse outcomes. However, the use of novel organ perfusion technology helped high-risk patients achieve similar outcomes as the benchmark cohort.

2022 - Comparison of long occlusive femoropopliteal de novo versus previous endovascularly treated lesions managed with in situ saphenous bypass [Articolo su rivista]
Troisi, N.; Michelagnoli, S.; Adami, D.; Berchiolli, R.; Accrocca, F.; Amico, A.; Angelini, A.; Arnuzzo, L.; Marchetti, A. A.; Attisani, L.; Bafile, G.; Baldino, G.; Barbanti, E.; Bartoli, S.; Bellosta, R.; Benedetto, F.; Borioni, R.; Briolini, F.; Busoni, C.; Camparini, S.; Cappiello, P.; Carbonari, L.; Casella, F.; Celoria, G.; Chiama, A.; Chisci, E.; Civilini, E.; Codispoti, F.; Conti, B.; Coppi, G.; De Blasis, G.; D'Elia, M.; Di Domenico, R.; Di Girolamo, C.; Ercolini, L.; Ferrari, A.; Ferrari, M.; Forliti, E.; Frigatti, P.; Frigerio, D.; Frosini, P.; Garriboli, L.; Giordano, A. N.; Guerrieri, W.; Jannello, A.; Massara, M.; Merlo, M.; Mezzetti, R.; Miccoli, T.; Milite, D.; Mingazzini, P.; Muncinelli, M.; Nano, G.; Natola, M.; Novali, C.; Palasciano, G.; Perkmann, R.; Persi, F.; Petruccelli, D.; Pinelli, M.; Poletto, G.; Porta, C.; Pratesi, C.; Pruner, G.; Ragazzi, G.; Righini, P.; Salvini, M.; Scovazzi, P.; Setacci, C.; Settembrini, A. M.; Siani, A.; Silingardi, R.; Silvestro, A.; Talarico, F.; Tolva, V.; Trani, A.; Trimarchi, S.; Tshomba, Y.; Vigliotti, G.; Viola, D.; Volpe, P.; Zani, F.
abstract

Background: The aim of this study was to compare the 2-year outcomes of de novo versus postendovascular lesion treatment of femoropopliteal occlusions included in a national, multicenter, observational, prospective registry based on the treatment of critical Limb-threatening IschaeMia with infragenicular Bypass adopting in situ SAphenous VEin technique (LIMBSAVE) registry. Methods: From January 2018 to December 2019, 541 patients from 43 centers have been enrolled in the LIMBSAVE registry. Of these patients, 460 were included in the present study: 341 (74.1%) with de novo lesions (DN group) and 119 (25.9%) with postendovascular treatment lesions (PE group). Initial outcome measures were assessed at 30 days after treatment. Furthermore, at the 2-year follow-up, the estimated outcomes of primary patency, primary-assisted patency, secondary patency, and limb salvage were analyzed with Kaplan-Meier curves and compared between groups with the log-rank test. Results: Both groups were homogeneous in terms of demographic data, preoperative risk factors, and clinical presentation. However, compared with DN group, more patients in PE group had a great saphenous vein diameter of less than 3 mm (11.1% vs 21%; P = .007). Intraoperatively, both groups showed similar distal anastomosis sites: below-the-knee popliteal artery (63% DN group, 66.4% PE group) and tibial vessel (37% DN group, 33.6% PE group) (P = .3). The overall mean duration of follow-up was 11.6 months (range, 1-24 months). At the 2-year follow-up, there were no differences between the two groups in terms of primary patency (66.3% DN group vs 74.1% PE group; P = .9), primary-assisted patency (78.2% DN group vs 79.5% PE group; P = .2), secondary patency (85.1% DN group vs 91.4% PE group; P = .2), and limb salvage (95.2% DN group vs 95.1% PE group; P = .9). Conclusions: The LIMBSAVE registry did not show a worsening of overall patency and limb salvages rates at the 2-year follow-up in patients undergoing in situ saphenous bypass after a failed endovascular approach for long femoropopliteal occlusive disease. This finding is in contrast with what has been published in literature.

2022 - Current practice of normothermic regional perfusion and machine perfusion in donation after circulatory death liver transplants in Italy [Articolo su rivista]
De Carlis, R.; Lauterio, A.; Centonze, L.; Buscemi, V.; Schlegel, A.; Muiesan, P.; De Carlis, L.; Carraro, A.; Ghinolfi, D.; De Simone, P.; Ravaioli, M.; Cescon, M.; Dondossola, D.; Bongini, M.; Mazzaferro, V.; Pagano, D.; Gruttadauria, S.; Gringeri, E.; Cillo, U.; Patrono, D.; Romagnoli, R.; Camagni, S.; Colledan, M.; Olivieri, T.; Di Benedetto, F.; Vennarecci, G.; Baccarani, U.; Lai, Q.; Rossi, M.; Manzia, T. M.; Tisone, G.; Vivarelli, M.; Scalera, I.; Lupo, L. G.; Andorno, E.; Meniconi, R. L.; Ettorre, G. M.; Avolio, A. W.; Agnes, S.; Pellegrino, R. A.; Zamboni, F.
abstract

Background: Normothermic regional perfusion (NRP) and machine perfusion (MP) are variously used in many European centers to improve the outcomes after liver transplantation from donation after circulatory death (DCD). In Italy, a combination of NRP and subsequent MP has been used since the start of the activity. While NRP is mandatory for every DCD recovery, the subsequent use of MP is left to each center. Methods: We have designed a national survey to investigate practices and policies of these techniques. The questionnaire included 46 questions and was distributed to all the 21 Italian centers using an online form between June and July 2021. Results: The overall response rate was 100%. A local NRP program for controlled Maastricht type 3 DCD was active in 11/21 (52.4%) centers. Organization and availability of personnel were perceived as the main difficulties in starting such a program. Between 2015 and 2020, 119 DCD livers were transplanted, with an overall utilization rate of 69.2%. Pump flow and gross aspect were considered the most reliable parameters in liver selection during NRP. Eight (72.7%) centers adopted subsequent hypothermic MP, 1 (9.1%) center normothermic MP, and the remaining 2 (18.2%) used both MP types. Conclusion: This first snapshot survey shows that NRP with subsequent MP is the most used protocol in Italy for DCD livers, although some heterogeneity exists in the type and purpose of MP between centers. Overall, this policy ensures a high utilization rate, considering the high risk of the DCD donor population in Italy. Graphical abstract: [Figure not available: see fulltext.]

2022 - Cytokine mass balance levels in donation after circulatory death donors using hemoadsorption: Case series report [Articolo su rivista]
Baroni, S.; Marudi, A.; Rinaldi, S.; Ghedini, S.; Magistri, P.; Piero Guerrini, G.; Olivieri, T.; Dallai, C.; Talamonti, M.; Maccieri, J.; Benedetto, F. D.; Bertellini, E.
abstract

The use of hemadsorption has been purposed to reduce cytokine levels during the reperfusion phase during donation after circulatory death (DCD) programs. This paper aims to describe a cases series of the inflammatory cytokine levels before and after hemadsorption during normothermic reperfusion in DCD donors of liver and kidneys. In this observational pilot paper, we describe 8 DCD donors of liver or kidneys in our center from the year 2018 to 2019. All DCD donor subjects had similar age, were younger than 60 years, without evident critical conditions, no liver or kidney dysfunction known, and they presented with poor neurological outcomes instrumentally and clinically documented. We observed in our patients an interesting reduction of IL-10 and TNF-α levels during the normothermic reperfusion with hemadsorption. We transplanted all livers and kidneys from DCD donors without significant compliances.

2022 - De Novo Skin Neoplasms in Liver-Transplanted Patients: Single-Center Prospective Evaluation of 105 Cases [Articolo su rivista]
Paganelli, Alessia; Magistri, Paolo; Kaleci, Shaniko; Chester, Johanna; Pezzini, Claudia; Catellani, Barbara; Ciardo, Silvana; Casari, Alice; Giusti, Francesca; Bassoli, Sara; Di Sandro, Stefano; Pellacani, Giovanni; Farnetani, Francesca; Di Benedetto, Fabrizio
abstract

Background and Objectives: Solid-organ transplant recipients (SOTRs) are notably considered at risk for developing cutaneous malignancies. However, most of the existing literature is focused on kidney transplant-related non-melanoma skin cancers (NMSCs). Conflicting data have been published so far on NMSC incidence among liver transplant recipients (LTRs), and whether LTRs really should be considered at lower risk remains controversial. The aim of the present study was to prospectively collect data on the incidence of cutaneous neoplasms in an LTR cohort. Materials and Methods: All LTRs transplanted at the Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit of Modena University Hospital from October 2015 to June 2021 underwent a post-transplant periodic skin check at the Dermatology Unit according to our institutional integrated care pathway. Data on the presence of cutaneous malignant and premalignant lesions were collected at every timepoint. Results: A total of 105 patients were enrolled in the present study. Nearly 15% of the patients developed cutaneous cancerous and/or precancerous lesions during the follow-up period. Almost half of the skin cancerous lesions were basal cell carcinomas. Actinic keratoses (AKs) were observed in six patients. Four patients developed in situ squamous cell carcinomas, and one patient was diagnosed with stage I malignant melanoma. Otherwise, well-established risk factors for the occurrence of skin tumors, such as skin phototype, cumulative sun exposure, and familial history of cutaneous neoplasms, seemed to have no direct impact on skin cancer occurrence in our cohort, as well as an immunosuppressive regimen and the occurrence of non-cutaneous neoplasms. Conclusions: Close dermatological follow-up is crucial for LTRs, and shared protocols of regular skin checks in this particular subset of patients are needed in transplant centers.

2022 - Endothelial angiopoietin-2 overexpression in explanted livers identifies subjects at higher risk of recurrence of hepatocellular carcinoma after liver transplantation [Articolo su rivista]
Lasagni, Simone; Leonardi, Filippo; Pivetti, Alessandra; Di Marco, Lorenza; Ravaioli, Federico; Serenari, Matteo; Gitto, Stefano; Critelli, Rosina Maria; Milosa, Fabiola; Romanzi, Adriana; Mancarella, Serena; Dituri, Francesco; Riefolo, Mattia; Catellani, Barbara; Magistri, Paolo; Romagnoli, Dante; Celsa, Ciro; Enea, Marco; de Maria, Nicola; Schepis, Filippo; Colecchia, Antonio; Cammà, Calogero; Cescon, Matteo; D'Errico, Antonietta; di Benedetto, Fabrizio; Giannelli, Gianluigi; Martinez-Chantar, Maria Luz; Villa, Erica
abstract

Background Though the precise criteria for accessing LT are consistently being applied, HCC recurrence (HCC-R_LT) still affects more than 15% of the patients. We analyzed the clinical, histopathological, and biological features of patients with HCC to identify the predictive factors associated with cancer recurrence and survival after LT.Methods We retrospectively analyzed 441 patients with HCC who underwent LT in our center. Overall, 70 (15.8%) of them developed HCC-R_LT. We matched them by age at transplant and etiology with 70 non-recurrent patients. A comparable cohort from the Liver Transplant Centre of Bologna served as validation. The clinical and biochemical characteristics and pre-LT criteria (Milan, Metroticket, Metroticket_AFP, and AFP model) were evaluated. Histological analysis and immunohistochemistry for angiopoietin-2 in the tumor and non-tumor tissue of explanted livers were performed. Patients' follow-up was until death, last clinical evaluation, or 31 December 2021. In patients with HCC-R_LT, the date of diagnosis of recurrence and anatomical site has been reported; if a biopsy of recurrence was available, histologic and immunohistochemical analyses were also performed.Results Patients were followed up for a mean period of 62.7 54.7 months (median, 39 months). A higher risk of HCC-R_LT was evident for factors related indirectly (AFP) or directly (endothelial angiopoietin-2, microvascular invasion) to biological HCC aggressiveness. In multivariate analysis, only angiopoietin-2 expression was independently associated with recurrence. Extremely high levels of endothelial angiopoietin-2 expression were also found in hepatic recurrence and all different metastatic locations. In univariate analysis, MELD, Metroticket_AFP Score, Edmondson-Steiner grade, microvascular invasion, and endothelial angiopoietin-2 were significantly related to survival. In multivariate analysis, angiopoietin-2 expression, Metroticket_AFP score, and MELD (in both training and validation cohorts) independently predicted mortality. In time-dependent area under receiver operating characteristic curve analysis, the endothelial angiopoietin-2 expression had the highest specificity and sensitivity for recurrence (AUC 0.922, 95% CI 0.876-0.962, p < 0.0001).Conclusions Endothelial angiopoietin-2 expression is a powerful independent predictor of post-LT tumor recurrence and mortality, highlighting the fundamental role of tumor biology in defining the patients' prognosis after liver transplantation. The great advantage of endothelial angiopoietin-2 is that it is evaluable in HCC biopsy before LT and could drive a patient's priority on the waiting list.

2022 - Extracorporeal interval support for organ retrieval delivery regional experience with sharing equipe, equipment & expertise to increase conventionally defined as controlled donor pool in time of pandemic [Articolo su rivista]
Circelli, A.; Antonini, M. V.; Gamberini, E.; Nanni, A.; Benni, M.; Castioni, C. A.; Gordini, G.; Maitan, S.; Piccioni, F.; Tarantino, G.; Prugnoli, M.; Spiga, M.; Altini, M.; Di Benedetto, F.; Cescon, M.; Solli, P.; Catena, F.; Ercolani, G.; Russo, E.; Agnoletti, V.
abstract

Donation after circulatory death (DCD) programs are expanding in Europe, in the attempt to expand donors pool. Even in controlled DCD donors, however, a protracted warm ischemia time occurring in the perimortem period might damage organs, making these unsuitable for transplantation. Implementing a strategy of extracorporeal interval support for organ retrieval (EISOR), a regional reperfusion with normothermic, oxygenated blood provides a physiologic environment allowing extensive assessment of potential grafts, and potentially promotes recovery of native function. Here we report the results of a multi-center retrospective cohort study including 29 Maastricht Category III controlled DCD donors undergoing extracorporeal support in a regional DCD/EISOR Training Center, and in the network of referring In-Training Centers, under the liaison of the regional Transplant Coordination Center during COVID-19 pandemic, between March 2020 and November 2021. The study aims to understand whether a mobile, experienced EISOR team implementing a consistent technique and sharing its equipe, expertise and equipment in a regional network of hospitals, might be effective and efficient in implementing the regional DCD program activity even in a highly stressed healthcare system.

2022 - Factors associated with and impact of open conversion on the outcomes of minimally invasive left lateral sectionectomies: An international multicenter study [Articolo su rivista]
Wang, H. P.; Yong, C. C.; Wu, A. G. R.; Cherqui, D.; Troisi, R. I.; Cipriani, F.; Aghayan, D.; Marino, M. V.; Belli, A.; Chiow, A. K. H.; Sucandy, I.; Ivanecz, A.; Vivarelli, M.; Di Benedetto, F.; Choi, S. -H.; Lee, J. H.; Park, J. O.; Gastaca, M.; Fondevila, C.; Efanov, M.; Rotellar, F.; Choi, G. -H.; Campos, R. R.; Wang, X.; Sutcliffe, R. P.; Pratschke, J.; Tang, C. N.; Chong, C. C.; D'Hondt, M.; Ruzzenente, A.; Herman, P.; Kingham, T. P.; Scatton, O.; Liu, R.; Ferrero, A.; Levi Sandri, G. B.; Soubrane, O.; Mejia, A.; Lopez-Ben, S.; Sijberden, J.; Monden, K.; Wakabayashi, G.; Sugioka, A.; Cheung, T. -T.; Long, T. C. D.; Edwin, B.; Han, H. -S.; Fuks, D.; Aldrighetti, L.; Abu Hilal, M.; Goh, B. K. P.; Chan, C. -Y.; Syn, N.; Prieto, M.; Schotte, H.; De Meyere, C.; Krenzien, F.; Schmelzle, M.; Lee, K. -F.; Salimgereeva, D.; Alikhanov, R.; Lee, L. S.; Jang, J. Y.; Labadie, K. P.; Kojima, M.; Kato, Y.; Fretland, A. A.; Ghotbi, J.; Coelho, F. F.; Pirola Kruger, J. A.; Lopez-Lopez, V.; Magistri, P.; Valle, B. D.; Casellas I Robert, M.; Mishima, K.; Ettorre, G. M.; Mocchegiani, F.; Kadam, P.; Pascual, F.; Saleh, M.; Mazzotta, A.; Montalti, R.; Giglio, M.; Lee, B.; D'Silva, M.; Nghia, P. P.; Lim, C.; Liu, Q.; Lai, E. C.
abstract

Background: Despite the rapid advances that minimally invasive liver resection has gained in recent decades, open conversion is still inevitable in some circumstances. In this study, we aimed to determine the risk factors for open conversion after minimally invasive left lateral sectionectomy, and its impact on perioperative outcomes. Methods: This is a post hoc analysis of 2,445 of 2,678 patients who underwent minimally invasive left lateral sectionectomy at 45 international centers between 2004 and 2020. Factors related to open conversion were analyzed via univariate and multivariate analyses. One-to-one propensity score matching was used to analyze outcomes after open conversion versus non-converted cases. Results: The open conversion rate was 69/2,445 (2.8%). On multivariate analyses, male gender (3.6% vs 1.8%, P =.011), presence of clinically significant portal hypertension (6.1% vs 2.6%, P =.009), and larger tumor size (50 mm vs 32 mm, P <.001) were identified as independent factors associated with open conversion. The most common reason for conversion was bleeding in 27/69 (39.1%) of cases. After propensity score matching (65 open conversion vs 65 completed via minimally invasive liver resection), the open conversion group was associated with increased operation time, blood transfusion rate, blood loss, and postoperative stay compared with cases completed via the minimally invasive approach. Conclusion: Male sex, portal hypertension, and larger tumor size were predictive factors of open conversion after minimally invasive left lateral sectionectomy. Open conversion was associated with inferior perioperative outcomes compared with non-converted cases.

2022 - Is minimally invasive liver surgery a reasonable option in recurrent HCC? A snapshot from the I Go MILS registry [Articolo su rivista]
Levi Sandri, G. B.; Colasanti, M.; Aldrighetti, L.; Guglielmi, A.; Cillo, U.; Mazzaferro, V.; Dalla Valle, R.; De Carlis, L.; Salvatore, G.; Di Benedetto, F.; Ferrero, A.; Ettorre, G. M.; Antonucci, A.; Batignani, G.; Belli, G.; Belli, A.; Berti, S.; Boggi, U.; Bonsignore, P.; Brolese, A.; Calise, F.; Ceccarelli, G.; Cecconi, S.; Colledan, M.; Coratti, A.; Ercolani, G.; Ferla, F.; Filauro, M.; Floridi, A.; Frena, A.; Giuliani, A.; Giuliante, F.; Grazi, G. L.; Gringeri, E.; Griseri, G.; Guerriero, S.; Jovine, E.; Magistri, P.; Maida, P.; Massani, M.; Mezzatesta, P.; Morelli, L.; Russolillo, N.; Navarra, G.; Parisi, A.; Patriti, A.; Ravaioli, M.; Ratti, F.; Romito, R.; Reggiani, P.; Ruzzenente, A.; Santambrogio, R.; Berardi, G.; Sgroi, G.; Slim, A.; Spada, M.; Sposito, C.; Tedeschi, U.; Tisone, G.; Torzilli, G.; Veneroni, L.; Vincenti, L.; Zamboni, F.; Zimmitti, G.
abstract

Laparoscopic liver resection (LLR) for Hepatocellular carcinoma (HCC) is a safe procedure. Repeat surgery is more often required, and the role of minimally invasive liver surgery (MILS) is not yet clearly defined. The present study analyzes data compiled by the Italian Group of Minimally Invasive Liver Surgery (IGoMILS) on LLR. To compare repeated LLR with the first LLR for HCC is the primary endpoint. The secondary endpoint was to evaluate the outcome of repeat LLR in the case of primary open versus primary MILS surgery. The data cohort is divided into two groups. Group 1: first liver resection and Group 2: Repeat LLR. To compare the two groups a 3:1 Propensity Score Matching is performed to analyze open versus MILS primary resection. Fifty-two centers were involved in the present study, and 1054 patients were enrolled. 80 patients underwent to a repeat LLR. The type of resection was different, with more major resections in the group 1 before matching the two groups. After propensity score matching 3:1, each group consisted of 222 and 74 patients. No difference between the two groups was observed. In the subgroup analysis, in 44 patients the first resection was performed by an open approach. The other 36 patients were resected with a MILS approach. We found no difference between these two subgroups of patients. The present study in repeat MILS for HCC using the IGoMILS Registry has observed the feasibility and safety of the MILS procedure.

2022 - Low-dose aspirin confers protection against acute cellular allograft rejection after primary liver transplantation [Articolo su rivista]
Oberkofler, C. E.; Raptis, D. A.; Muller, P. C.; Sousa da Silva, R. X.; Lehmann, K.; Ito, T.; Owen, T.; Pollok, J. -M.; Parente, A.; Schlegel, A.; Peralta, P.; Winter, E.; Selzner, M.; Fodor, M.; Maglione, M.; Jaklitsch, M.; Marques, H. P.; Chavez-Villa, M.; Contreras, A.; Kron, P.; Lodge, P.; Alford, S.; Rana, A.; Magistri, P.; Di Benedetto, F.; Johnson, B.; Kirchner, V.; Bauldrick, F.; Halazun, K. J.; Ghamarnedjad, O.; Mehrabi, A.; Basto, S. T.; Fernandes, E. S. M.; Paladini, J.; de Santibanes, M.; Florman, S.; Tabrizian, P.; Dutkowski, P.; Clavien, P. -A.; Busuttil, R. W.; Kaldas, F. M.; Petrowsky, H.
abstract

This study investigated the effect of low-dose aspirin in primary adult liver transplantation (LT) on acute cellular rejection (ACR) as well as arterial patency rates. The use of low-dose aspirin after LT is practiced by many transplant centers to minimize the risk of hepatic artery thrombosis (HAT), although solid recommendations do not exist. However, aspirin also possesses potent anti-inflammatory properties and might mitigate inflammatory processes after LT, such as rejection. Therefore, we hypothesized that the use of aspirin after LT has a protective effect against ACR. This is an international, multicenter cohort study of primary adult deceased donor LT. The study included 17 high-volume LT centers and covered the 3-year period from 2013 to 2015 to allow a minimum 5-year follow-up. In this cohort of 2365 patients, prophylactic antiplatelet therapy with low-dose aspirin was administered in 1436 recipients (61%). The 1-year rejection-free survival rate was 89% in the aspirin group versus 82% in the no-aspirin group (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.63–0.94; p = 0.01). The 1-year primary arterial patency rates were 99% in the aspirin group and 96% in the no-aspirin group with an HR of 0.23 (95% CI, 0.13–0.40; p < 0.001). Low-dose aspirin was associated with a lower risk of ACR and HAT after LT, especially in the first vulnerable year after transplantation. Therefore, low-dose aspirin use after primary LT should be evaluated to protect the liver graft from ACR and to maintain arterial patency.

2022 - Migration rate using fully covered metal stent in anastomotic strictures after liver transplantation: Results from the BASALT study group [Articolo su rivista]
Conigliaro, R.; Pigo, F.; Bertani, H.; Greco, S.; Burti, C.; Indriolo, A.; Di Sario, A.; Ortolani, A.; Maroni, L.; Tringali, A.; Barbaro, F.; Costamagna, G.; Magarotto, A.; Masci, E.; Mutignani, M.; Forti, E.; Tringali, A.; Parodi, M. C.; Assandri, L.; Marrone, C.; Fantin, A.; Penagini, R.; Cantu, P.; Di Benedetto, F.; Ravelli, P.; Vivarelli, M.; Agnes, S.; Mazzaferro, V.; De Carlis, L.; Andorno, E.; Cillo, U.; Rossi, G.
abstract

Background and Study Aim: The traditional endoscopic therapy of anastomotic strictures (AS) after orthotopic liver transplantation (OLT) is multiple ERCPs with the insertion of an increasing number of plastic stents side-by-side. Fully covered self-expanding metal stents (cSEMS) could be a valuable option to decrease the number of procedures needed or non-responders to plastic stents. This study aims to retrospectively analyse the results of AS endoscopic treatment by cSEMS and to identify any factors associated with its success. Patients and Methods: Ninety-one patients (mean age 55.9 ± 7.6 SD; 73 males) from nine Italian transplantation centres, had a cSEMS positioned for post-OLT-AS between 2007 and 2017. Forty-nine (54%) patients were treated with cSEMS as a second-line treatment. Results: All the procedures were successfully performed without immediate complications. After ERCP, adverse events occurred in 11% of cases (2 moderate pancreatitis and 8 cholangitis). In 49 patients (54%), cSEMSs migrated. After cSEMS removal, 46 patients (51%) needed further endoscopic (45 patients) or radiological (1 patient) treatments to solve the AS. Lastly, seven patients underwent surgery. Multivariable stepwise logistic regression showed that cSEMS migration was the only factor associated with further treatments (OR 2.6, 95% CI 1.0–6.6; p value 0.03); cSEMS implantation before 12 months from OLT was associated with stent migration (OR 5.2, 95% CI 1.7–16.0; p value 0.004). Conclusions: cSEMS appears to be a safe tool to treat AS. cSEMS migration is the main limitation to its routinary implantation and needs to be prevented, probably with the use of new generation anti-migration stents.

2022 - Perihilar-cholangiocarcinoma: what really matters? [Articolo su rivista]
Di Benedetto, Fabrizio; Magistri, Paolo; Di Sandro, Stefano
abstract

2022 - Predictors of solid extra-hepatic non-skin cancer in liver transplant recipients and analysis of survival: a long-term follow-up study [Articolo su rivista]
Gitto, Stefano; Magistri, Paolo; Marzi, Luca; Mannelli, Nicolò; De Maria, Nicola; Mega, Andrea; Vitale, Giovanni; Valente, Giovanna; Vizzutti, Francesco; Villa, Erica; Marra, Fabio; Andreone, Pietro; Di Benedetto, Fabrizio; Falcini, Margherita; Catellani, Barbara; Guerrini, Gian Piero; Serra, Valentina; Di Sandro, Stefano; Ballarin, Roberto; Piai, Guido; Schepis, Filippo; Margotti, Marzia; Cursaro, Carmela; De Simone, Paolo; Petruccelli, Stefania; Carrai, Paola; Forte, Paolo; Campani, Claudia; Zoller, Heinz
abstract

Introduction and objectives: De novo malignancies represent an important cause of death for liver transplant recipients. Our aim was to analyze predictors of extra-hepatic non-skin cancer (ESNSC) and the impact of ESNSC on the long-term outcome. Patients: We examined data from patients transplanted between 2000 and 2005 and followed-up in five Italian transplant clinics with a retrospective observational cohort study. Cox Regression was performed to identify predictors of ESNSC. A 1:2 cohort sub-study was developed to analyze the impact of ESNSC on 10-year survival. Results: We analyzed data from 367 subjects (median follow-up: 15 years). Patients with ESNSC (n=47) more often developed post-LT diabetes mellitus (DM) (57,4% versus 35,9%, p=0,004). At multivariate analysis, post-LT DM independently predicted ESNSC (HR 1.929, CI 1.029-3.616, p=0.040). Recipients with ESNSC showed a lower 10-year survival than matched controls (46,8% versus 68,1%, p=0,023). Conclusions: Post-LT DM seems to be a relevant risk factor for post-LT ESNSC. ESNSC could have a noteworthy impact on the long-term survival of LT recipients.

2022 - Propensity Score-Matched Analysis Comparing Robotic and Laparoscopic Right and Extended Right Hepatectomy [Articolo su rivista]
Chong, C. C.; Fuks, D.; Lee, K. -F.; Zhao, J. J.; Choi, G. H.; Sucandy, I.; Chiow, A. K. H.; Marino, M. V.; Gastaca, M.; Wang, X.; Lee, J. H.; Efanov, M.; Kingham, T. P.; D'Hondt, M.; Troisi, R. I.; Choi, S. -H.; Sutcliffe, R. P.; Chan, C. -Y.; Lai, E. C. H.; Park, J. O.; Di Benedetto, F.; Rotellar, F.; Sugioka, A.; Coelho, F. F.; Ferrero, A.; Long, T. C. D.; Lim, C.; Scatton, O.; Liu, Q.; Schmelzle, M.; Pratschke, J.; Cheung, T. -T.; Liu, R.; Han, H. -S.; Tang, C. N.; Goh, B. K. P.
abstract

Importance: Laparoscopic and robotic techniques have both been well adopted as safe options in selected patients undergoing hepatectomy. However, it is unknown whether either approach is superior, especially for major hepatectomy such as right hepatectomy or extended right hepatectomy (RH/ERH). Objective: To compare the outcomes of robotic vs laparoscopic RH/ERH. Design, Setting, and Participants: In this case-control study, propensity score matching analysis was performed to minimize selection bias. Patients undergoing robotic or laparoscopic RH/EHR at 29 international centers from 2008 to 2020 were included. Interventions: Robotic vs laparoscopic RH/ERH. Main Outcomes and Measures: Data on patient demographics, tumor characteristics, and short-term perioperative outcomes were collected and analyzed. Results: Of 989 individuals who met study criteria, 220 underwent robotic and 769 underwent laparoscopic surgery. The median (IQR) age in the robotic RH/ERH group was 61.00 (51.86-69.00) years and in the laparoscopic RH/ERH group was 62.00 (52.03-70.00) years. Propensity score matching resulted in 220 matched pairs for further analysis. Patients' demographics and tumor characteristics were comparable in the matched cohorts. Robotic RH/ERH was associated with a lower open conversion rate (19 of 220 [8.6%] vs 39 of 220 [17.1%]; P =.01) and a shorter postoperative hospital stay (median [IQR], 7.0 [5.0-10.0] days; mean [SD], 9.11 [7.52] days vs median [IQR], 7.0 [5.75-10.0] days; mean [SD], 9.94 [8.99] days; P =.048). On subset analysis of cases performed between 2015 and 2020 after a center's learning curve (50 cases), robotic RH/ERH was associated with a shorter postoperative hospital stay (median [IQR], 6.0 [5.0-9.0] days vs 7.0 [6.0-9.75] days; P =.04) with a similar conversion rate (12 of 220 [7.6%] vs 17 of 220 [10.8%]; P =.46). Conclusion and Relevance: Robotic RH/ERH was associated with a lower open conversion rate and shorter postoperative hospital stay compared with laparoscopic RH/ERH. The difference in open conversion rate was associated with a significant decrease for laparoscopic but not robotic RH/ERH after a center had mounted the learning curve. Use of robotic platform may help to overcome the initial challenges of minimally invasive RH/ERH.

2022 - Pure laparoscopic versus robotic liver resections: Multicentric propensity score-based analysis with stratification according to difficulty scores [Articolo su rivista]
Cipriani, F.; Fiorentini, G.; Magistri, P.; Fontani, A.; Menonna, F.; Annecchiarico, M.; Lauterio, A.; De Carlis, L.; Coratti, A.; Boggi, U.; Ceccarelli, G.; Di Benedetto, F.; Aldrighetti, L.
abstract

Background: The benefits of pure laparoscopic and robot-assisted liver resections (LLR and RALR) are known in comparison to open surgery. The aim of the present retrospective comparative study is to investigate the role of RALR and LLR according to different levels of difficulty. Methods: The institutional databases of six high-volume hepatobiliary centers were retrospectively reviewed. The study population was divided in two groups: LLR and RALR. The procedures were stratified for difficulty levels accordingly to three classifications. A propensity score matching was implemented to mitigate selection bias. Short-term outcomes were the object of comparison. Results: Nine hundred and thirty-six LLR and 403 RALR were collected. RALR exhibited fewer cases of intraoperative blood loss, lower transfusion and conversion rates (especially for oncological radicality) than LLR in the setting of highly difficult operations, whereas LLR had lower postoperative morbidity and fewer low-grade complications. For intermediate and low-difficulty resections, the intraoperative advantages of RALR gradually decreased to nonsignificant results and LLR remained associated with lower postoperative morbidity. Conclusion: Robot-assisted liver resections do not show operative nor clinically significant benefits over LLR for low- and intermediate-difficulty resections. By reducing conversion rates, RALR can favour the operative feasibility of difficult resections possibly extending the indications of minimally invasive approaches for liver resection.

2022 - Quality of life in liver transplant recipients during the Corona virus disease 19 pandemic: A multicentre study [Articolo su rivista]
Gitto, S.; Golfieri, L.; Mannelli, N.; Tame, M. R.; Lopez, I.; Ceccato, R.; Montanari, S.; Falcini, M.; Vitale, G.; De Maria, N.; Presti, D. L.; Marzi, L.; Mega, A.; Valente, G.; Borghi, A.; Foschi, F. G.; Grandi, S.; Forte, P.; Cescon, M.; Di Benedetto, F.; Andreone, P.; Arcangeli, G.; De Simone, P.; Bonacchi, A.; Sofi, F.; Morelli, M. C.; Petranelli, M.; Lau, C.; Marra, F.; Chiesi, F.; Vizzutti, F.; Vero, V.; Di Donato, R.; Berardi, S.; Pianta, P.; D'Anzi, S.; Schepis, F.; Gualandi, N.; Miceli, F.; Villa, E.; Piai, G.; Valente, M.; Campani, C.; Lynch, E.; Magistri, P.; Cursaro, C.; Chiarelli, A.; Carrai, P.; Petruccelli, S.; Dinu, M.; Pagliai, G.
abstract

Background: Liver transplant recipients require specific clinical and psychosocial attention given their frailty. Main aim of the study was to assess the quality of life after liver transplant during the current pandemic. Methods: This multicentre study was conducted in clinically stable, liver transplanted patients. Enrollment opened in June and finished in September 2021. Patients completed a survey including lifestyle data, quality of life (Short Form health survey), sport, employment, diet. To examine the correlations, we calculated Pearson coefficients while to compare subgroups, independent samples t-tests and ANOVAs. To detect the predictors of impaired quality of life, we used multivariable logistic regression analysis. Results: We analysed data from 511 patients observing significant associations between quality of life’s physical score and both age and adherence to Mediterranean diet (p <.01). A significant negative correlation was observed between mental score and the sedentary activity (p <.05). Female patients scored significantly lower than males in physical and mental score. At multivariate analysis, females were 1.65 times more likely to report impaired physical score than males. Occupation and physical activity presented significant positive relation with quality of life. Adherence to Mediterranean diet was another relevant predictor. Regarding mental score, female patients were 1.78 times more likely to show impaired mental score in comparison with males. Sedentary activity and adherence to Mediterranean diet were further noteworthy predictors. Conclusions: Females and subjects with sedentary lifestyle or work inactive seem to show the worst quality of life and both physical activity and Mediterranean diet might be helpful to improve it.

2022 - Robotic liver partition and portal vein embolization for staged hepatectomy for perihilar cholangiocarcinoma [Articolo su rivista]
Di Benedetto, F.; Magistri, P.; Guerrini, G. P.; Di Sandro, S.
abstract

Perihilar cholangiocarcinoma (pCCA) is one of the most complex challenges for hepatobiliary surgeons. Poor results and high incidence of morbidity after Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) for pCCA discouraged this indication. It has been proposed that minimally invasive approach for ALPPS first stage, as well as combination of surgical liver partition and radiologic portal vein embolization (PVE), may improve outcomes reducing interstage morbidity. We report a case of right trisectionectomy with enbloc caudatectomy ALPPS scheduled for pCCA with robotic approach at stage-1, the full video is provided as supplementary material. Due to intraoperative presence of portal vein tumor infiltration during hilar dissection (no evidence in the pre-operative work-up), a radiologic right PVE was performed after stage-1 instead of portal vein ligation, followed by portal vein resection and biductal hepatico-jejunostomy at stage-2 with open approach. The patient was a 74-year-old female diagnosed with 3-cm mass-forming pCCA. The total clean liver volume was 1231 cc, with future liver remnant (FLR) volume of 25.1% (segments II and III). She was discharged in the interstage interval on postoperative day (POD) 4; CT scan on POD 12 showed that FLR increased up to 33% (369 cc) (Fig. 1). ALPPS was completed on POD 17, the postoperative course was uneventful, and the patient was discharged in good general condition on POD 19 after stage-2. Besides the already demonstrated advantages in terms of reduced interstage morbidity, robotic ALPPS represents a promising strategy to expand surgical indication in patients with pCCA. The combination of liver partition and PVE may increase the opportunities to perform radical resections in selected patients with pCCA and portal vein infiltration.

2022 - R3-AFP score is a new composite tool to refine prediction of hepatocellular carcinoma recurrence after liver transplantation [Articolo su rivista]
Costentin, C.; Pinero, F.; Degroote, H.; Notarpaolo, A.; Boin, I. F.; Boudjema, K.; Baccaro, C.; Podesta, L. G.; Bachellier, P.; Ettorre, G. M.; Poniachik, J.; Muscari, F.; Dibenedetto, F.; Duque, S. H.; Salame, E.; Cillo, U.; Marciano, S.; Vanlemmens, C.; Fagiuoli, S.; Burra, P.; Van Vlierberghe, H.; Cherqui, D.; Lai, Q.; Silva, M.; Rubinstein, F.; Duvoux, C.; Conti, F.; Scatton, O.; Bernard, P. H.; Francoz, C.; Durand, F.; Dharancy, S.; Woehl, M. -L.; Laurent, A.; Radenne, S.; Dumortier, J.; Abergel, A.; Barbier, L.; Houssel-Debry, P.; Pageaux, G. P.; Chiche, L.; Deledinghen, V.; Hardwigsen, J.; Gugenheim, J.; Altieri, M.; Hilleret, M. N.; Decaens, T.; Chagas, A.; Costa, P.; Cristina de Ataide, E.; Quinones, E.; Marciano, S.; Anders, M.; Varon, A.; Zerega, A.; Soza, A.; Machaca, M. P.; Arufe, D.; Menendez, J.; Zapata, R.; Vilatoba, M.; Munoz, L.; Menendez, R. C.; Maraschio, M.; Mccormack, L.; Mattera, J.; Gadano, A.; Fatima Boin, I. S. F.; Parente Garcia, J. H.; Carrilho, F.; Magini, G.; Miglioresi, L.; Gambato, M.; Di Benedetto, F.; D'Ambrosio, C.; Vitale, A.; Colledan, M.; Pinelli, D.; Magistri, P.; Vennarecci, G.; Colasanti, M.; Giannelli, V.; Pellicelli, A.; Baccaro, C.; Eduard, C.; Samuele, I.; Jeroen, D.; Jonas, S.; Jacques, P.; Chris, V.; Dirk, Y.; Peter, M.; Valerio, L.; Christophe, M.; Olivier, D.; Jean, D.; Roberto, T.; Paul, L. J.
abstract

Background & Aims: Patients with hepatocellular carcinoma (HCC) are selected for liver transplantation (LT) based on pre-LT imaging ± alpha-foetoprotein (AFP) level, but discrepancies between pre-LT tumour assessment and explant are frequent. Our aim was to design an explant-based recurrence risk reassessment score to refine prediction of recurrence after LT and provide a framework to guide post-LT management. Methods: Adult patients who underwent transplantation between 2000 and 2018 for HCC in 47 centres were included. A prediction model for recurrence was developed using competing-risk regression analysis in a European training cohort (TC; n = 1,359) and tested in a Latin American validation cohort (VC; n=1,085). Results: In the TC, 76.4% of patients with HCC met the Milan criteria, and 89.9% had an AFP score of ≤2 points. The recurrence risk reassessment (R3)-AFP model was designed based on variables independently associated with recurrence in the TC (with associated weights): ≥4 nodules (sub-distribution of hazard ratio [SHR] = 1.88, 1 point), size of largest nodule (3–6 cm: SHR = 1.83, 1 point; >6 cm: SHR = 5.82, 5 points), presence of microvascular invasion (MVI; SHR = 2.69, 2 points), nuclear grade >II (SHR = 1.20, 1 point), and last pre-LT AFP value (101–1,000 ng/ml: SHR = 1.57, 1 point; >1,000 ng/ml: SHR = 2.83, 2 points). Wolber's c-index was 0.76 (95% CI 0.72–0.80), significantly superior to an R3 model without AFP (0.75; 95% CI 0.72–0.79; p = 0.01). Four 5-year recurrence risk categories were identified: very low (score = 0; 5.5%), low (1–2 points; 15.1%), high (3–6 points; 39.1%), and very high (>6 points; 73.9%). The R3-AFP score performed well in the VC (Wolber's c-index of 0.78; 95% CI 0.73–0.83). Conclusions: The R3 score including the last pre-LT AFP value (R3-AFP score) provides a user-friendly, standardised framework to design post-LT surveillance strategies, protocols, or adjuvant therapy trials for HCC not limited to the Milan criteria. Clinical Trials Registration: NCT03775863. Lay summary: Considering discrepancies between pre-LT tumour assessment and explant are frequent, reassessing the risk of recurrence after LT is critical to further refine the management of patients with HCC. In a large and international cohort of patients who underwent transplantation for HCC, we designed and validated the R3-AFP model based on variables independently associated with recurrence post-LT (number of nodules, size of largest nodule, presence of MVI, nuclear grade, and last pre-LT AFP value). The R3-AFP model including last available pre-LT AFP value outperformed the original R3 model only based on explant features. The final R3-AFP scoring system provides a robust framework to design post-LT surveillance strategies, protocols, or adjuvant therapy trials, irrespective of criteria used to select patients with HCC for LT.

2022 - Salvage versus Primary Liver Transplantation for Hepatocellular Carcinoma: A Twenty-Year Experience Meta-Analysis [Articolo su rivista]
Guerrini, G. P.; Esposito, G.; Olivieri, T.; Magistri, P.; Ballarin, R.; Di Sandro, S.; Di Benedetto, F.
abstract

(1) Background: Primary liver transplantation (PLT) for HCC represents the ideal treatment. However, since organ shortage increases the risk of drop-out from the waiting list for tumor progression, a new surgical strategy has been developed: Salvage Liver Transplantation (SLT) can be offered as an additional curative strategy for HCC recurrence after liver resection. The aim of this updated meta-analysis is to compare surgical and long-term outcomes of SLT versus PLT for HCC. (2) Materials and Methods: A systematic review and meta-analysis was conducted using the published papers comparing SLT and PLT up to January 2022. (3) Results: 25 studies describing 11,275 patients met the inclusion criteria. The meta-analysis revealed no statistical difference in intraoperative blood loss, overall vascular complications, retransplantation rate, and hospital stay in the SLT group compared with the PLT group. However, the SLT group showed a slightly significant lower 5-year OS rate and 5-year disease-free survival rate. (4) Conclusion: meta-analysis advocates the relative safety and feasibility of both Salvage LT and Primary LT strategies. Specifically, SLT seems to have comparable surgical outcomes but slightly poorer long-term survival than PLT.

2022 - Variations in risk-adjusted outcomes following 4318 laparoscopic liver resections [Articolo su rivista]
Cucchetti, A.; Aldrighetti, L.; Ratti, F.; Ferrero, A.; Guglielmi, A.; Giuliante, F.; Cillo, U.; Mazzaferro, V.; De Carlis, L.; Ercolani, G.; Ettorre, G. M.; di Benedetto, F.; Valle, R. D.; Gruttadauria, S.; Jovine, E.; Boggi, U.; Vincenti, L.; Santambrogio, R.; Giuliani, A.; Torzilli, G.; Zimmiti, G.; Brolese, A.; Belli, A.; Ravaioli, M.; Frena, A.; Rossi, G. E.; Grazi, G. L.; Zamboni, F.; Berti, S.; Calise, F.; Massani, M.; Morelli, L.; Filauro, M.; Tisone, G.; Coratti, A.; Navarra, G.; Romito, R.; Ceccarelli, G.; Belli, G.; Griseri, G.; Antonucci, A.; Mezzatesta, P.; Veneroni, L.; Schiavo, M.; Colledan, M.; Parisi, A.; Guerriero, S.; Spada, M.; Batignani, G.; Sgroi, G.; Floridi, P.; Boni, L.; Maida, P.; Ribero, D.; La Barba, G.
abstract

Background/Purpose: Quality measures in surgery are important to establish appropriate levels of care and to develop improvement strategies. The purpose of this study was to provide risk-adjusted outcome measures after laparoscopic liver resection (LLR). Methods: Data from a prospective, multicenter database involving 4318 patients submitted to LLRs in 41 hospitals from an intention-to-treat approach (2014–2020) were used to analyze heterogeneity (I2) among centers and to develop a risk-adjustment model on outcome measures through multivariable mixed-effect models to account for confounding due to case-mix. Results: Involved hospitals operated on very different patients: the largest heterogeneity was observed for operating in the presence of previous abdominal surgery (I2:79.1%), in cirrhotic patients (I2:89.3%) suffering from hepatocellular carcinoma (I2:88.6%) or requiring associated intestinal resections (I2:82.8%) and in regard to technical complexity (I2 for the most complex LLRs: 84.1%). These aspects determined substantial or large heterogeneity in overall morbidity (I2:84.9%), in prolonged in-hospital stay (I2:86.9%) and in conversion rate (I2:73.4%). Major complication had medium heterogeneity (I2:46.5%). The heterogeneity of mortality was null. Risk-adjustment accounted for all of this variability and the final risk-standardized conversion rate was 8.9%, overall morbidity was 22.1%, major morbidity was 5.1% and prolonged in-hospital stay was 26.0%. There were no outliers among the 41 participating centers. An online tool was provided. Conclusions: A benchmark for LLRs including all eligible patients was provided, suggesting that surgeons can act accordingly in the interest of the patient, modifying their approach in relation to different indications and different experience, but finally providing the same quality of care.

2021 - An Italian survey on the use of T-tube in liver transplantation: old habits die hard! [Articolo su rivista]
Pravisani, R.; De Simone, P.; Patrono, D.; Lauterio, A.; Cescon, M.; Gringeri, E.; Colledan, M.; Di Benedetto, F.; di Francesco, F.; Antonelli, B.; Manzia, T. M.; Carraro, A.; Vivarelli, M.; Regalia, E.; Vennarecci, G.; Guglielmo, N.; Cesaretti, M.; Avolio, A. W.; Valentini, M. F.; Lai, Q.; Baccarani, U.
abstract

There is enough clinical evidence that a T-tube use in biliary reconstruction at adult liver transplantation (LT) does not significantly modify the risk of biliary stricture/leak, and it may even sustain infective and metabolic complications. Thus, the policy on T-tube use has been globally changing, with progressive application of more restrictive selection criteria. However, there are no currently standardized indications in such change, and many LT Centers rely only on own experience and routine. A nation-wide survey was conducted among all the 20 Italian adult LT Centers to investigate the current policy on T-tube use. It was found that 20% of Centers completely discontinued the T-tube use, while 25% Centers used it routinely in all LT cases. The remaining 55% of Centers applied a selective policy, based on criteria of technical complexity of biliary reconstruction (72.7%), followed by low-quality graft (63.6%) and high-risk recipient (36.4%). A T-tube use > 50% of annual caseload was not associated with high-volume Center status (> 70 LT per year), an active pediatric or living-donor transplant program, or use of DCD grafts. Only 10/20 (50%) Centers identified T-tube as a potential risk factor for complications other than biliary stricture/leak. In these cases, the suspected pathogenic mechanism comprised bacterial colonization (70%), malabsorption (70%), interruption of the entero-hepatic bile-acid cycle (50%), biliary inflammation due to an indwelling catheter (40%) and gut microbiota changes (40%). In conclusion, the prevalence of T-tube use among the Italian LT Centers is still relatively high, compared to the European trend (33%), and the potential detrimental effect of T-tube, beyond biliary stricture/leak, seems to be somehow underestimated.

2021 - Breakthrough invasive fungal infection after liver transplantation in patients on targeted antifungal prophylaxis: a prospective multicentre study [Articolo su rivista]
Rinaldi, Matteo; Bartoletti, Michele; Ferrarese, Alberto; Franceschini, Erica; Campoli, Caterina; Coladonato, Simona; Pascale, Renato; Tedeschi, Sara; Gatti, Milo; Cricca, Monica; Ambretti, Simone; Siniscalchi, Antonio; Morelli, Maria Cristina; Cescon, Matteo; Cillo, Umberto; Di Benedetto, Fabrizio; Burra, Patrizia; Mussini, Cristina; Cristini, Francesco; Lewis, Russell; Viale, Pierluigi; Giannella, Maddalena
abstract

OBJECTIVE: To investigate the rate of and the risk factors for breakthrough-IFI (b-IFI) after orthotopic liver transplantation (OLT) according to the new definition proposed by Mycoses-Study-Group-Education-and-Research-Consortium (MSG-ERC) and the European-Confederation-of-Medical-Mycology (ECMM).METHODS: Multicenter prospective study of adult patients who underwent OLT at three Italian hospitals, from January 2015 to December 2018. Targeted antifungal prophylaxis (TAP) protocol was developed and shared among participating centers. Follow-up was 1-year after OLT. B-IFI was defined as infection occurring during exposure to antifungal prophylaxis. Risk factors for b-IFI were analysed among patients exposed to prophylaxis by univariable analysis.RESULTS: We enrolled 485 OLT patients. Overall compliance to TAP protocol was 64.3%, 220 patients received antifungal prophylaxis, 172 according to TAP protocol. Twenty-nine patients were diagnosed of IFI within 1 year after OLT. Of them, 11 presented with b-IFI within 17 (IQR 11-33) and 16 (IQR 4-30) days from OLT and from antifungal onset, respectively. Then out of 11 patients with b-IFI were classified as having high risk of IFI and were receiving anti-mould prophylaxis, nine with echinocandins and one with polyenes. Comparison of patients with and without b-IFI showed significant differences for prior Candida colonization, need of renal replacement therapy after OLT, re-operation, and CMV infection (whole blood CMV-DNA >100,000 copies/mL). Although non-significant, a higher rate of b-IFI in patients on echinocandins was observed (8.2% vs. 1.8%, p=0.06).CONCLUSIONS: We observed 5% of b-IFI among OLT patients exposed to antifungal prophylaxis. The impact of echinocandins on b-IFI risk in this setting should be further explored.

2021 - Clinical implications of malnutrition in the management of patients with pancreatic cancer: Introducing the concept of the nutritional oncology board [Articolo su rivista]
Rovesti, G.; Valoriani, F.; Rimini, M.; Bardasi, C.; Ballarin, R.; Di Benedetto, F.; Menozzi, R.; Dominici, M.; Spallanzani, A.
abstract

Pancreatic cancer represents a very challenging disease, with an increasing incidence and an extremely poor prognosis. Peculiar features of this tumor entity are represented by pancreatic exocrine insufficiency and an early and intense nutritional imbalance, leading to the highly prevalent and multifactorial syndrome known as cancer cachexia. Recently, also the concept of sarcopenic obesity has emerged, making the concept of pancreatic cancer malnutrition even more multifaceted and complex. Overall, these nutritional derangements play a pivotal role in contributing to the dismal course of this malignancy. However, their relevance is often underrated and their assessment is rarely applied in clinical daily practice with relevant negative impact for patients’ outcome in neoadjuvant, surgical, and metastatic settings. The proper detection and management of pancreatic cancer-related malnutrition syndromes are of primary importance and deserve a specific and multidisciplinary (clinical nutrition, oncology, etc.) approach to improve survival, but also the quality of life. In this context, the introduction of a “Nutritional Oncology Board” in routine daily practice, aimed at assessing an early systematic screening of patients and at implementing nutritional support from the time of disease diagnosis onward seems to be the right path to take.

2021 - Correction to: Immunosuppressive regimens for adult liver transplant recipients in real-life practice: consensus recommendations from an Italian Working Group (Hepatology International, (2020), 14, 6, (930-943), 10.1007/s12072-020-10091-5) [Articolo su rivista]
Cillo, U.; De Carlis, L.; Del Gaudio, M.; De Simone, P.; Fagiuoli, S.; Lupo, F.; Tisone, G.; Volpes, R.; Avolio, A.; Bitetto, D.; Boccagni, P.; Carraro, A.; Castellaneta, A.; Colledan, M.; De Maria, N.; Di Benedetto, F.; Lanza, A. G.; Gardini, I.; Guglielmo, N.; Invernizzi, F.; Laurenzi, A.; Leandro, G.; Lenci, I.; Lorenzin, D.; Mameli, L.; Manzia, T. M.; Mariani, A.; Mennini, G.; Mirabella, S.; Morelli, M. C.; Nicolini, D.; Petruccelli, S.; Regalia, E.; Reggiani, P.; Roselli, S.; Zamboni, F.
abstract

A correction to this paper has been published: https://doi.org/10.1007/s12072-021-10178-7

2021 - Correction to: Is minimally invasive liver surgery a reasonable option in recurrent HCC? A snapshot from the I Go MILS registry (Updates in Surgery, (2021), 10.1007/s13304-021-01161-w) [Articolo su rivista]
Levi Sandri, G. B.; Colasanti, M.; Aldrighetti, L.; Guglielmi, A.; Cillo, U.; Mazzaferro, V.; Dalla Valle, R.; De Carlis, L.; Gruttadauria, S.; Di Benedetto, F.; Ferrero, A.; Ettorre, G. M.; Antonucci, A.; Batignani, G.; Belli, G.; Belli, A.; Berti, S.; Boggi, U.; Bonsignore, P.; Brolese, A.; Calise, F.; Ceccarelli, G.; Cecconi, S.; Colledan, M.; Coratti, A.; Ercolani, G.; Ferla, F.; Filauro, M.; Floridi, A.; Frena, A.; Giuliani, A.; Giuliante, F.; Grazi, G. L.; Gringeri, E.; Griseri, G.; Guerriero, S.; Jovine, E.; Magistri, P.; Maida, P.; Massani, M.; Mezzatesta, P.; Morelli, L.; Russolillo, N.; Navarra, G.; Parisi, A.; Patriti, A.; Ravaioli, M.; Ratti, F.; Romito, R.; Reggiani, P.; Ruzzenente, A.; Santambrogio, R.; Berardi, G.; Sgroi, G.; Slim, A.; Spada, M.; Sposito, C.; Tedeschi, U.; Tisone, G.; Torzilli, G.; Veneroni, L.; Vincenti, L.; Zamboni, F.; Zimmitti, G.
abstract

In the originally published article the co-author first name and last name was interchanged. The correct name is copied below Salvatore Gruttadauria The original article has been updated.

2021 - How to Preserve Liver Grafts From Circulatory Death With Long Warm Ischemia? A Retrospective Italian Cohort Study With Normothermic Regional Perfusion and Hypothermic Oxygenated Perfusion [Articolo su rivista]
De Carlis, Riccardo; Schlegel, Andrea; Frassoni, Samuele; Olivieri, Tiziana; Ravaioli, Matteo; Camagni, Stefania; Patrono, Damiano; Bassi, Domenico; Pagano, Duilio; Di Sandro, Stefano; Lauterio, Andrea; Bagnardi, Vincenzo; Gruttadauria, Salvatore; Cillo, Umberto; Romagnoli, Renato; Colledan, Michele; Cescon, Matteo; Di Benedetto, Fabrizio; Muiesan, Paolo; De Carlis, Luciano
abstract

Donation after circulatory death (DCD) in Italy, given its 20-min stand-off period, provides a unique bench-test for normothermic regional perfusion (NRP) and dual hypothermic oxygenated machine perfusion (D-HOPE).

2021 - International study on the outcome of locoregional therapy for liver transplant in hepatocellular carcinoma beyond Milan criteria [Articolo su rivista]
Degroote, Helena; Piñero, Federico; Costentin, Charlotte; Notarpaolo, Andrea; Boin, Ilka F; Boudjema, Karim; Baccaro, Cinzia; Chagas, Aline Lopes; Bachellier, Philippe; Ettorre, Giuseppe Maria; Poniachik, Jaime; Muscari, Fabrice; Di Benedetto, Fabrizio; Duque, Sergio Hoyos; Salame, Ephrem; Cillo, Umberto; Gadano, Adrián; Vanlemmens, Claire; Fagiuoli, Stefano; Rubinstein, Fernando; Burra, Patrizia; Cherqui, Daniel; Silva, Marcelo; Van Vlierberghe, Hans; Duvoux, Christophe
abstract

Background & Aims: Good outcomes after liver transplantation (LT) have been reported after successfully downstaging to Milan criteria in more advanced hepatocellular carcinoma (HCC). We aimed to compare post-LT outcomes in patients receiving locoregional therapies (LRT) before LT according to Milan criteria and University of California San Francisco downstaging (UCSF-DS) protocol and 'all-comers'.Methods: This multicentre cohort study included patients who received any LRT before LT from Europe and Latin America (2000-2018). We excluded patients with alpha-foetoprotein (AFP) above 1,000 ng/ml. Competing risk regression analysis for HCC recurrence was conducted, estimating subdistribution hazard ratios (SHRs) and corresponding 95% CIs.Results: From 2,441 LT patients, 70.1% received LRT before LT (n = 1,711). Of these, 80.6% were within Milan, 12.0% within UCSF-DS, and 7.4% all-comers. Successful downstaging was achieved in 45.2% (CI 34.8-55.8) and 38.2% (CI 25.4-52.3) of the UCSF-DS group and all-comers, respectively. The risk of recurrence was higher for all-comers (SHR 6.01 [p <0.0001]) and not significantly higher for the UCSF-DS group (SHR 1.60 [p = 0.32]), compared with patients remaining within Milan. The allcomers presented more frequent features of aggressive HCC and higher tumour burden at explant. Among the UCSF-DS group, an AFP value of QO ng/ml at listing was associated with lower recurrence (SHR 2.01 [p = 0.006]) and better survival. However, recurrence was still significantly high irrespective of AFP 520 ng/ml in all-comers.Conclusions: Patients within the UCSF-DS protocol at listing have similar post-transplant outcomes compared with those within Milan when successfully downstaged. Meanwhile, all-comers have a higher recurrence and inferior survival irrespective of response to LRT. Additionally, in the UCSF-DS group, an ALP of 520 ng/ml might be a novel tool to optimise selection of candidates for LT. (C) 2021 The Authors. Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL).Lay summary: Patients with more extended HCC (within the UCSF-DS protocol) successfully downstaged to the conventional Milan criteria do not have a higher recurrence rate after LT compared with the group remaining in the Milan criteria from listing to transplantation. Moreover, in the UCSF-DS patient group, an ALP value equal to or below 20 ng/ml at listing might be a novel tool to further optimise selection of candidates for LT. (C) 2021 The Authors. Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL).

2021 - Laparoscopic major hepatectomy for hepatocellular carcinoma in elderly patients: a multicentric propensity score‑based analysis [Articolo su rivista]
Delvecchio, Antonella; Conticchio, Maria; Ratti, Francesca; Gelli, Maximiliano; Anelli, Ferdinando Massimiliano; Laurent, Alexis; Vitali, Giulio Cesare; Magistri, Paolo; Assirati, Giacomo; Felli, Emanuele; Wakabayashi, Taiga; Pessaux, Patrick; Piardi, Tullio; Di Benedetto, Fabrizio; De'Angelis, Nicola; Briceño-Delgado, Javier; Adam, Rene; Cherqui, Daniel; Aldrighetti, Luca; Memeo, Riccardo
abstract

Considering the increase in overall life expectancy and the rising incidence of hepatocellular carcinoma (HCC), more elderly patients are considered for hepatic resection. Traditionally, major hepatectomy has not been proposed to the elderly due to severe comorbidities. Indeed, only a few case series are reported in the literature. The present study aimed to compare short-term and long-term outcomes between laparoscopic major hepatectomy (LMH) and open major hepatectomy (OMH) in elderly patients with HCC using propensity score matching (PSM).

2021 - Laparoscopic surgery versus radiofrequency ablation for the treatment of single hepatocellular carcinoma ≤3 cm in the elderly: a propensity score matching analysis [Articolo su rivista]
Conticchio, M.; Delvecchio, A.; Ratti, F.; Gelli, M.; Anelli, F. M.; Laurent, A.; Vitali, G. C.; Magistri, P.; Assirati, G.; Felli, E.; Wakabayashi, T.; Pessaux, P.; Piardi, T.; Di Benedetto, F.; De'Angelis, N.; Javier Briceno, D. F.; Rampoldi, A. G.; Adam, R.; Cherqui, D.; Aldrighetti, L.; Memeo, R.
abstract

Background: Laparoscopic liver resection (LLR) and radiofrequency ablation (RFA) represented potential treatments for patients with a single hepatocellular carcinoma (HCC) smaller than 3 cm. As the aging population soared, our study aimed to examine the advantage/drawback balance for these treatments, which should be reassessed in elderly patients. Methods: A multicentric retrospective study compared 184 elderly patients (aged >70 years) (86 patients underwent LLR and 98 had RFA) with single ≤3 cm HCC, observed from January 2009 to January 2019. Results: After propensity score matching (PSM), the estimated 1- and 3-year overall survival rates were 96.5 and 87.9% for the LLR group, and 94.6 and 68.1% for the RFA group (p = 0.001) respectively. The estimated 1- and 3-year disease-free survival rates were 92.5 and 67.4% for the LLR group, and 68.5 and 36.9% for the RFA group (p = 0.001). Patients with HCC of anterolateral segments were more often treated with laparoscopic resection (47 vs. 36, p = 0.04). The median operative time in the resection group was 205 min and 25 min in the RFA group (p = 0.01). Length of hospital stay was 5 days in the resection group and 3 days in the RFA group (p = 0.03). Conclusion: Despite a longer length of hospital stay and operative time, LLR guarantees a comparable postoperative course and a better overall and disease-free survival in elderly patients with single HCC (≤3 cm), located in anterolateral segments.

2021 - Laparoscopic versus open liver resection for hepatocellular carcinoma in elderly patients: a propensity score matching analysis [Articolo su rivista]
Delvecchio, A.; Conticchio, M.; Riccelli, U.; Ferraro, V.; Ratti, F.; Gelli, M.; Anelli, F. M.; Laurent, A.; Vitali, G. C.; Magistri, P.; Assirati, G.; Felli, E.; Wakabayashi, T.; Pessaux, P.; Piardi, T.; Di Benedetto, F.; De'Angelis, N.; Briceno-Delgado, J.; Adam, R.; Cherqui, D.; Aldrighetti, L.; Memeo, R.
abstract

Background: Surgical resection is a first-line curative option for hepatocellular carcinoma, but its role is still unclear in elderly patients. The aim of our study was to compare short- and long-term outcomes of laparoscopic and open liver resection in elderly patients with hepatocellular carcinoma. Methods: The study included 665 consecutive hepatocellular carcinoma liver resection cases in patients with ≥70 years of age treated in eight European hospital centres. Patients were divided into laparoscopic and open liver resection groups. Perioperative and long-term outcomes were compared between these groups. Results: After a 1:1 propensity score matching, 219 patients were included in each group. Clavien-Dindo grades III/IV (6 vs. 20%, p = 0.04) were lower in the laparoscopic than in the open matched group. Hospital stay was shorter in the laparoscopic than in the open matched group (5 vs. 7 days, p < 0.001). There were no significant differences between laparoscopic and open groups regarding overall survival and disease-free survival at 1-, 3- and 5- year periods. Conclusion: Laparoscopic liver resection for hepatocellular carcinoma is associated with good short-term outcomes in patients with ≥70 years of age compared to open liver resection. Laparoscopic liver resection is safe and feasible in elderly patients with hepatocellular carcinoma.

2021 - Laparoscopic versus open right posterior sectionectomy: an international, multicenter, propensity score-matched evaluation [Articolo su rivista]
van der Heijde, N.; Ratti, F.; Aldrighetti, L.; Benedetti Cacciaguerra, A.; Can, M. F.; D'Hondt, M.; Di Benedetto, F.; Ivanecz, A.; Magistri, P.; Menon, K.; Papoulas, M.; Vivarelli, M.; Besselink, M. G.; Abu Hilal, M.
abstract

Background: Although laparoscopic liver resection has become the standard for minor resections, evidence is lacking for more complex resections such as the right posterior sectionectomy (RPS). We aimed to compare surgical outcomes between laparoscopic (LRPS) and open right posterior sectionectomy (ORPS). Methods: An international multicenter retrospective study comparing patients undergoing LRPS or ORPS (January 2007—December 2018) was performed. Patients were matched based on propensity scores in a 1:1 ratio. Primary endpoint was major complication rate defined as Accordion ≥ 3 grade. Secondary endpoints included blood loss, length of hospital stay (LOS) and resection status. A sensitivity analysis was done excluding the first 10 LRPS patients of each center to correct for the learning curve. Additionally, possible risk factors were explored for operative time, blood loss and LOS. Results: Overall, 399 patients were included from 9 centers from 6 European countries of which 150 LRPS could be matched to 150 ORPS. LRPS was associated with a shorter operative time [235 (195–285) vs. 247 min (195–315) p = 0.004], less blood loss [260 (188–400) vs. 400 mL (280–550) p = 0.009] and a shorter LOS [5 (4–7) vs. 8 days (6–10), p = 0.002]. Major complication rate [n = 8 (5.3%) vs. n = 9 (6.0%) p = 1.00] and R0 resection rate [144 (96.0%) vs. 141 (94.0%), p = 0.607] did not differ between LRPS and ORPS, respectively. The sensitivity analysis showed similar findings in the previous mentioned outcomes. In multivariable regression analysis blood loss was significantly associated with the open approach, higher ASA classification and malignancy as diagnosis. For LOS this was the open approach and a malignancy. Conclusion: This international multicenter propensity score-matched study showed an advantage in favor of LRPS in selected patients as compared to ORPS in terms of operative time, blood loss and LOS without differences in major complications and R0 resection rate.

2021 - Liver resection vs radiofrequency ablation in single hepatocellular carcinoma of posterosuperior segments in elderly patients [Articolo su rivista]
Delvecchio, Antonella; Inchingolo, Riccardo; Laforgia, Rita; Ratti, Francesca; Gelli, Maximiliano; Anelli, Massimiliano Ferdinando; Laurent, Alexis; Vitali, Giulio; Magistri, Paolo; Assirati, Giacomo; Felli, Emanuele; Wakabayashi, Taiga; Pessaux, Patrick; Piardi, Tullio; di Benedetto, Fabrizio; De'Angelis, Nicola; Briceño, Javier; Rampoldi, Antonio; Adam, Renè; Cherqui, Daniel; Aldrighetti, Luca Antonio; Memeo, Riccardo
abstract

Background: Liver resection and radiofrequency ablation are considered curative options for hepatocellular carcinoma. The choice between these techniques is still controversial especially in cases of hepatocellular carcinoma affecting posterosuperior segments in elderly patients. Aim: To compare post-operative outcomes between liver resection and radiofrequency ablation in elderly with single hepatocellular carcinoma located in posterosuperior segments. Methods: A retrospective multicentric study was performed enrolling 77 patients age ≥ 70-years-old with single hepatocellular carcinoma (≤ 30 mm), located in posterosuperior segments (4a, 7, 8). Patients were divided into liver resection and radiofrequency ablation groups and preoperative, peri-operative and long-term outcomes were retrospectively analyzed and compared using a 1:1 propensity score matching. Results: After propensity score matching, twenty-six patients were included in each group. Operative time and overall postoperative complications were higher in the resection group compared to the ablation group (165 min vs 20 min, P < 0.01; 54% vs 19% P = 0.02 respectively). A median hospital stay was significantly longer in the resection group than in the ablation group (7.5 d vs 3 d, P < 0.01). Ninety-day mortality was comparable between the two groups. There were no significant differences between resection and ablation group in terms of overall survival and disease free survival at 1, 3, and 5 years. Conclusion: Radiofrequency ablation in posterosuperior segments in elderly is safe and feasible and ensures a short hospital stay, better quality of life and does not modify the overall and disease-free survival.

2021 - Liver transplantation for hcc in hiv‐infected patients: Long‐term single‐center experience [Articolo su rivista]
Guerrini, G. P.; Berretta, M.; Guaraldi, G.; Magistri, P.; Esposito, G.; Ballarin, R.; Serra, V.; Di Sandro, S.; Di Benedetto, F.
abstract

Background: HIV‐infected patients now have long life expectation since the introduction of the highly active antiretroviral therapy (HAART). Liver diseases, especially cirrhosis and hepatocellular carcinoma (HCC), currently represent a leading cause of death in this setting of patients. Aim: To address the results of liver transplantation (LT) for HCC in HIV‐infected patients. Methods: All patients with and without HIV infection who underwent LT for HCC (n = 420) between 2001 and 2021 in our center were analyzed with the intent of comparing graft and patient survival. Cox regression analysis was used to determine prognostic survival factors and logistic regression to determine the predictor factors of post‐LT recurrence. Results: Among 1010 LT, 32 were HIV‐infected recipients. With an average follow‐up of 62 ± 51 months, 5‐year overall survival in LT recipients with and without HIV‐infection was 71.6% and 69.9%, respectively (p = ns), whereas 5‐year graft survival in HIV‐infected and HIV‐non infected was 68.3% and 68.2%, respectively (p = ns). The independent predictive factor of survival in the study group was: HCV infection (HR 1.83 p = 0.024). There were no significant differences in the pathological characteristics of HCC between the two groups. The logistic regression analysis of the study population demonstrated that microvascular invasion (HR 5.18 p< 0.001), HCC diameter (HR 1.16 p = 0.028), and number of HCC nodules (HR 1.26 p = 0.003) were predictors of recurrence post‐LT. Conclusion: Our study shows that HIV patients undergoing LT for HCC have comparable results in terms of post‐LT survival. Excellent results can be achieved for HIV-infected patients with HCC, as long as a strategy of close surveillance and precise treatment of the tumor is adopted while on the waiting list.

2021 - Major robotic hepatectomies: technical considerations [Articolo su rivista]
Magistri, P.; Assirati, G.; Ballarin, R.; Di Sandro, S.; Di Benedetto, F.
abstract

Robotic approach to the liver may allow to perform difficult resections with a minimally invasive strategy in an easier way as compared to standard laparoscopy. The aim of this study is to review our experience with robotic major hepatectomies, reporting technical considerations, and describing the outcomes of patients that underwent either left (LRH) or right robotic hepatectomy (RRH). Our prospectively maintained database was screened to identify all patients that received a major liver resection for benign or malignant disease. Preoperative data and postoperative short-term and long-term outcomes were reported. 261 robotic procedures were performed in our Center between May 2014 and October 2020. 12 patients underwent robotic left hepatectomy (RLH) and 10 patients were treated by robotic right hepatectomy (RRH). In the RLH group, median operative time (OT) was 383 min, median estimated blood loss (EBL) was 300 ml, and median in-hospital stay was of 3 days. In the RRH group, median OT was 490 min, median EBL 725 ml, and median hospital stay was 5 days. Although one of the advantages of minimally invasive surgery is to obtain radical resections with parenchyma sparing strategies, patients that need a major hepatectomy may benefit of a robotic resection with good postoperative outcomes. Team learning curve and growth instead of personal progression is crucial to expand the limits of novel surgical techniques.

2021 - Preoperative predictors of liver decompensation after mini-invasive liver resection [Articolo su rivista]
Sposito, C.; Monteleone, M.; Aldrighetti, L.; Cillo, U.; Dalla Valle, R.; Guglielmi, A.; Ettorre, G. M.; Ferrero, A.; Di Benedetto, F.; Rossi, G. E.; De Carlis, L.; Giuliante, F.; Mazzaferro, V.
abstract

Background: Post-hepatectomy liver failure (PHLF) represents the most frequent complication after liver surgery, and the most common cause of morbidity and mortality. Aim of the study is to identify the predictors of PHLF after mini-invasive liver surgery in cirrhosis and chronic liver disease, and to develop a model for risk prediction. Methods: The present study is a multicentric prospective cohort study on 490 consecutive patients who underwent mini-invasive liver resection from the Italian Registry of Mini-invasive Liver Surgery (I go MILS). Retrospective additional biochemical and clinical data were collected. Results: On 490 patients (26.5% females), PHLF occurred in 89 patients (18.2%). The only independent predictors of PHLF were Albumin-Bilirubin (ALBI) score (OR 3.213; 95% CI 1.661–6.215; p <.0.0001) and presence of ascites (OR 3.320; 95% CI 1.468–7.508; p = 0.004). Classification and regression tree (CART) modeling led to the identification of three risk groups: PHLF occurred in 23/217 patients with ALBI grade 1 (10.6%, low risk group), in 54/254 patients with ALBI score 2 or 3 and absence of ascites (21.3%, intermediate risk group) and in 12/19 patients with ALBI score 2 or 3 and evidence of ascites (63.2%, high risk group), p < 0.0001. The three groups showed a corresponding increase in postoperative complications (20.0%, 27.5% and 66.7%), Comprehensive Complication Index (5.1 ± 11.1, 6.0 ± 10.9 and 18.8 ± 18.9) and hospital stay (6.0 ± 4.0, 6.0 ± 6.0 and 8.0 ± 5.0 days). Conclusion: The risk of PHLF can be stratified by determining two easily available preoperative factors: ALBI and ascites. This model of risk prediction offers an objective instrument for a correct clinical decision-making.

2021 - Proximal Splenic Artery Embolization to Treat Refractory Ascites in a Patient With Cirrhosis [Articolo su rivista]
Caporali, C.; Turco, L.; Prampolini, F.; Quaretti, P.; Bianchini, M.; Saltini, D.; Miceli, F.; Casari, F.; Felaco, D.; Garcia-Pagan, J. C.; Trebicka, J.; Senzolo, M.; Guerrini, G. P.; Di Benedetto, F.; Torricelli, P.; Villa, E.; Schepis, F.
abstract

2021 - Radiofrequency ablation vs surgical resection in elderly patients with hepatocellular carcinoma in Milan criteria [Articolo su rivista]
Conticchio, M.; Inchingolo, R.; Delvecchio, A.; Laera, L.; Ratti, F.; Gelli, M.; Anelli, F.; Laurent, A.; Vitali, G.; Magistri, P.; Assirati, G.; Felli, E.; Wakabayashi, T.; Pessaux, P.; Piardi, T.; di Benedetto, F.; De'Angelis, N.; Briceno&, Tild; Rampoldi, A.; Adam, R.; Cherqui, D.; Aldrighetti, L. A.; Memeo, R.
abstract

BACKGROUND Surgical resection and radiofrequency ablation (RFA) represent two possible strategy in treatment of hepatocellular carcinoma (HCC) in Milan criteria. AIM To evaluate short- A nd long-term outcome in elderly patients (70 years) with HCC in Milan criteria, which underwent liver resection (LR) or RFA. METHODS The study included 594 patients with HCC in Milan criteria (429 in LR group and 165 in RFA group) managed in 10 European centers. Statistical analysis was performed using the Kaplan-Meier method before and after propensity score matching (PSM) and Cox regression. RESULTS After PSM, we compared 136 patients in the LR group with 136 patients in the RFA group. Overall survival at 1, 3, and 5 years was 91%, 80%, and 76% in the LR group and 97%, 67%, and 41% in the RFA group respectively (P = 0.001). Diseasefree survival at 1, 3, and 5 years was 84%, 60% and 44% for the LR group, and 63%, 36%, and 25% for the RFA group (P = 0.001).Postoperative Clavien-Dindo IIIIV complications were lower in the RFA group (1% vs 11%, P = 0.001) in association with a shorter length of stay (2 d vs 7 d, P = 0.001).In multivariate analysis, Model for End-stage Liver Disease (MELD) score (10) [odds ratio (OR) = 1.89], increased value of international normalized ratio (1.3) (OR = 1.60), treatment with radiofrequency (OR = 1.46) ,and multiple nodules (OR = 1.19) were independent predictors of a poor overall survival while a high MELD score (10) (OR = 1.51) and radiofrequency (OR = 1.37) were independent factors associated with a higher recurrence rate. CONCLUSION Despite a longer length of stay and a higher rate of severe postoperative complications, surgery provided better results in long-term oncological outcomes as compared to ablation in elderly patients (70 years) with HCC in Milan criteria. © 2021 The Author(s). Published by Baishideng Publishing Group Inc. All rights reserved.

2021 - Sarco-Model: A score to predict the dropout risk in the perspective of organ allocation in patients awaiting liver transplantation [Articolo su rivista]
Lai, Quirino; Magistri, Paolo; Lionetti, Raffaella; Avolio, Alfonso W; Lenci, Ilaria; Giannelli, Valerio; Pecchi, Annarita; Ferri, Flaminia; Marrone, Giuseppe; Angelico, Mario; Milana, Martina; Schinniná, Vincenzo; Menozzi, Renata; Di Martino, Michele; Grieco, Antonio; Manzia, Tommaso M; Tisone, Giuseppe; Agnes, Salvatore; Rossi, Massimo; Di Benedetto, Fabrizio; Ettorre, Giuseppe M
abstract

BACKGROUND & AIMS: Sarcopenia in liver transplantation (LT) cirrhotic candidates has been connected with higher dropouts and graft losses after transplant. The study aims to create an "urgency" model combining sarcopenia and MELDNa to predict the risk of dropout and identify an appropriate threshold of post-LT futility.METHODS: A total of 1,087 adult cirrhotic patients were listed for a first LT during Jan2012-Dec2018. The study population was split into a Training (n=855) and a Validation Set (n=232).RESULTS: Using a competing-risk analysis of cause-specific hazards, we created the Sarco-Model2 . According to the model, one extra-point of MELDNa was added for each 0.5-cm2 /m2 reduction of Total Psoas Area (TPA)<6.0 cm2 /m2 . At external validation, the Sarco-Model2 showed the best diagnostic ability for predicting the risk of 3-month dropout in patients with MELDNa<20 (AUC=0.93; p=0.003). Using the net reclassification improvement, 14.3% of dropped-out patients were correctly reclassified using the Sarco-Model2 . As for the futility threshold, transplanted patients with TPA<6.0 cm2 /m2 and MELDNa 35-40 (n=16/833, 1.9%) had the worse results (6-month graft loss=25.5%).CONCLUSIONS: In sarcopenic patients with MELDNa<20, the "urgency" Sarco-Model2 , should be used to prioritize the list, while MELDNa value should be preferred in patients with MELDNa ≥20. The Sarco-Model2 played a role in more than 30% of the cases in the investigated allocation scenario. In sarcopenic patients with a MELDNa value of 35-40, "futile" transplantation should be considered.

2021 - The COVID-19 second wave risk and liver transplantation: lesson from the recent past and the unavoidable need of living donors [Articolo su rivista]
Di Sandro, S.; Magistri, P.; Bagnardi, V.; Catellani, B.; Guerrini, G. P.; Di Benedetto, F.
abstract

2021 - The Italian Consensus on minimally invasive simultaneous resections for synchronous liver metastasis and primary colorectal cancer: A Delphi methodology [Articolo su rivista]
Rocca, A.; Cipriani, F.; Belli, G.; Berti, S.; Boggi, U.; Bottino, V.; Cillo, U.; Cescon, M.; Cimino, M.; Corcione, F.; De Carlis, L.; Degiuli, M.; De Paolis, P.; De Rose, A. M.; D'Ugo, D.; Di Benedetto, F.; Elmore, U.; Ercolani, G.; Ettorre, G. M.; Ferrero, A.; Filauro, M.; Giuliante, F.; Gruttadauria, S.; Guglielmi, A.; Izzo, F.; Jovine, E.; Laurenzi, A.; Marchegiani, F.; Marini, P.; Massani, M.; Mazzaferro, V.; Mineccia, M.; Minni, F.; Muratore, A.; Nicosia, S.; Pellicci, R.; Rosati, R.; Russolillo, N.; Spinelli, A.; Spolverato, G.; Torzilli, G.; Vennarecci, G.; Vigano, L.; Vincenti, L.; Delrio, P.; Calise, F.; Aldrighetti, L.
abstract

At the time of diagnosis synchronous colorectal cancer, liver metastases (SCRLM) account for 15–25% of patients. If primary tumour and synchronous liver metastases are resectable, good results may be achieved performing surgical treatment incorporated into the chemotherapy regimen. So far, the possibility of simultaneous minimally invasive (MI) surgery for SCRLM has not been extensively investigated. The Italian surgical community has captured the need and undertaken the effort to establish a National Consensus on this topic. Four main areas of interest have been analysed: patients’ selection, procedures, techniques, and implementations. To establish consensus, an adapted Delphi method was used through as many reiterative rounds were needed. Systematic literature reviews were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses instructions. The Consensus took place between February 2019 and July 2020. Twenty-six Italian centres participated. Eighteen clinically relevant items were identified. After a total of three Delphi rounds, 30-tree recommendations reached expert consensus establishing the herein presented guidelines. The Italian Consensus on MI surgery for SCRLM indicates possible pathways to optimise the treatment for these patients as consensus papers express a trend that is likely to become shortly a standard procedure for clinical pictures still on debate. As matter of fact, no RCT or relevant case series on simultaneous treatment of SCRLM are available in the literature to suggest guidelines. It remains to be investigated whether the MI technique for the simultaneous treatment of SCRLM maintain the already documented benefit of the two separate surgeries.

2021 - Total robotic ALPPS approach for hepatocellular carcinoma in cirrhotic liver [Articolo su rivista]
Fernandes, E. D. S. M.; de Barros, F.; Magistri, P.; Di Sandro, S.; Rezende de Carvalho, P.; Roza da Silva, F.; Andrade, R. O.; Pimentel, L. S.; Girao, C. L.; Pedreira de Mello, F.; Torres, O. J. M.; Di Benedetto, F.
abstract

Background: Hepatocellular carcinoma (HCC) is a common indication for associating liver partition with portal vein ligation for staged hepatectomy (ALPPS). Robotic liver resection has been done for HCC, but robotic ALPPS is a rare procedure. Methods: To present three cases of totally robotic ALPPS in cirrhotic patients with HCC. Results: Three cirrhotic male patients with HCC underwent ALPPS; the mean age was 54.3 years. MELD score was ≤9 and tumour size between 90 and 140 mm. The mean hypertrophy of the future liver remnant after the first stage was 77.5% and no postoperative liver failure was reported. Mean operative time of stage 1 was 7:30 h and of stage 2 was 4:37 h, without blood transfusion. The mean hospital stay for the first stage was 10 days and for the second stage was 9.3 days. No postoperative complication was recorded. Conclusions: Robotic ALPPS in cirrhotic patients with HCC is safe and feasible.

2021 - TRAIL receptors are expressed in both malignant and stromal cells in pancreatic ductal adenocarcinoma [Articolo su rivista]
Dall'Ora, Massimiliano; Rovesti, Giulia; Reggiani Bonetti, Luca; Casari, Giulia; Banchelli, Federico; Fabbiani, Luca; Veronesi, Elena; Petrachi, Tiziana; Magistri, Paolo; Di Benedetto, Fabrizio; Spallanzani, Andrea; Chiavelli, Chiara; Spano, Maria Carlotta; Maiorana, Antonino; Dominici, Massimo; Grisendi, Giulia
abstract

: This study assesses the expression of all TNF-related apoptosis-inducing ligand (TRAIL) receptors in pancreatic ductal adenocarcinoma (PDAC) tumor tissue. We aimed to include TRAIL receptor expression as an inclusion parameter in a future clinical study using a TRAIL-based therapy approach for PDAC patients. Considering the emerging influence of PDAC desmoplastic stroma on the efficacy of anti-PDAC therapies, this analysis was extended to tumor stromal cells. Additionally, we performed PDAC stroma characterization. Our retrospective cohort study (N=50) included patients with histologically confirmed PDAC who underwent surgery. The expression of TRAIL receptors (DR4, DR5, DcR1, DcR2, and OPG) in tumor and stromal cells was evaluated by immunohistochemistry (IHC). The amount of tumor stroma was assessed by anti-vimentin IHC and Mallory's trichrome staining. The prognostic impact was determined by the univariate Cox proportional hazards regression model. An extensive expression of functional receptors DR4 and DR5 and a variable expression of decoy receptors were detected in PDAC tumor and stromal cells. Functional receptors were detected also in metastatic tumor and stromal cells. A poor prognosis was associated with low or absent expression of decoy receptors in tumor cells of primary PDAC. After assessing that almost 80% of tumor mass was composed of stroma, we correlated a cellular-dense stroma in primary PDAC with reduced relapse-free survival. We demonstrated that TRAIL functional receptors are widely expressed in PDAC, representing a promising target for TRAIL-based therapies. Further, we demonstrated that a low expression of DcR1 and the absence of OPG in tumor cells, as well as a cellular-dense tumor stroma, could negatively impact the prognosis of PDAC patients.

2021 - Trauma and donation after circulatory death: a case series from a major trauma center [Articolo su rivista]
Circelli, A.; Brogi, E.; Gamberini, E.; Russo, E.; Benni, M.; Scognamiglio, G.; Nanni, A.; Coccolini, F.; Forfori, F.; Fugazzola, P.; Ansaloni, L.; Solli, P.; Benedetto, F. D.; Cescon, M.; Agnoletti, V.
abstract

Even with encouraging recipient outcomes, transplantation using donation after circulatory death (DCD) is still limited. A major barrier to this type of transplantation is the consequences of warm ischemia on graft survival; however, preservation techniques may reduce the consequences of cardiac arrest and provide better organ conservation. Furthermore, DCD in trauma patients could further expand organ donation. We present five cases in which organs were retrieved and transplanted successfully using normothermic regional perfusion (NRP) in trauma patients. Prompt critical care support and surgical treatment allowed us to overcome the acute phase. Unfortunately, owing to the severity of their injuries, all of the donors died. However, the advanced and continuous organ-specific supportive treatment allowed the maintenance of general clinical stability and organ preservation. Consequently, it was possible to retrieve and transplant the donors’ organs. Death was ascertained in accordance with cardio-circulatory criteria, which was followed by NRP. We consider that DCD in trauma patients may represent an important source of organs.

2020 - ASO Author Reflections: Robotic ALPPS: The Future is Coming [Articolo su rivista]
Di Benedetto, F.; Magistri, P.
abstract

2020 - Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) procedure for cholangiocarcinoma [Articolo su rivista]
Balci, D.; Sakamoto, Y.; Li, J.; Di Benedetto, F.; Kirimker, E. O.; Petrowsky, H.
abstract

Perihilar cholangiocarcinoma (PHCC) has been a great challenge for surgeons, requiring advanced skills and expertise and was often associated with high morbidity and mortality. Resectability rates are up to 75% even in experienced centers. In patients with PHCC, radical liver and bile duct resection aiming R0 surgical margins offers the best long-term survival. Therefore, extensive resections with low FLR are commonly needed and PVE is offered to induce remnant liver hypertrophy for a long period. Associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) is considered a promising approach inducing rapid remnant hypertrophy to prevent dropouts due to complications or tumor progression and increase resectability. Although poor results were reported initially, refinements in technique and risk adjustment of patient selection improved outcomes. The procedure is still under debate for the indication of PHCC. This article reviews the current literature on ALPPS in treatment of perihilar and intrahepatic cholangiocarcinoma.

2020 - Common bile duct lesions - how cholangioscopy helps rule out intraductal papillary neoplasms of the bile duct: A case report [Articolo su rivista]
Cocca, Silvia; Grande, Giuseppe; Reggiani Bonetti, Luca; Magistri, Paolo; Di Sandro, Stefano; Di Benedetto, Fabrizio; Conigliaro, Rita; Bertani, Helga
abstract

BACKGROUNDIntraductal papillary neoplasm of the bile duct (IPNB) is a rare variant of bile duct tumors, characterized by an exophytic growth exhibiting a papillary mass within the bile duct lumen and it can be localized anywhere along the biliary tree, with morphological variations and occasional invasion.CASE SUMMARYWe present a patient with obstructive jaundice who was diagnosed with IPNB using cholangioscopy during endoscopic retrograde cholangio-pancreatography. Using the SpyGlass DS II technology, we were able to define tumor extension and obtain targeted Spy-byte biopsies. After multidisciplinary evaluation, the patient was scheduled for surgical resection of the tumor, which was radically removed.CONCLUSIONCholangioscopy appears to be crucial for the rapid and clear diagnosis of lesions in the bile duct to achieve radical surgical resection.

2020 - Current management of portal vein thrombosis in liver transplantation [Articolo su rivista]
Bhangui, P.; Fernandes, E. S. M.; Di Benedetto, F.; Joo, D. -J.; Nadalin, S.
abstract

Nontumoral portal vein thrombosis (PVT) is present at liver transplantation (LT) in 5–26% of cirrhotic patients, and is known to affect post LT outcomes. Up to 31% of patients who are found to have PVT at the time of LT, would have had PVT at the time of initial listing, but others develop PVT during the waiting period. Adequate screening and treatment of the PVT on the waiting list for LT is thus essential so that a portoportal anastomoses can be performed at the time of LT. Early PVT (Yerdel Grade I/II) can be usually managed by thrombectomy, whereas Grade III PVT may require a jump graft from the superior mesenteric vein to the graft PV. Complete portomesenteric thrombosis is a huge challenge, and sometimes a cause for denying a LT in these patients, with multivisceral transplant being the only alternative. The presence of spontaneous, or previously surgically created portosytemic shunts like the leinorenal shunt, may serve as a good inflow option (renoportal anastomosis) in these patients to establish a physiological reconstruction. Although challenging, good outcomes are possible in patients with complex PVT if the appropriate surgical technique is chosen to ensure portal inflow and resolution of PHT post LT.

2020 - Current update in domino liver transplantation [Articolo su rivista]
Marques, H. P.; Barros, I.; Li, J.; Murad, S. D.; di Benedetto, F.
abstract

Orthotopic liver transplantation is an established treatment for end stage liver diseases as well as for some severe metabolic disorders. With increasing number of patients on the waiting list and the ongoing shortage of livers available, domino liver transplantation (DLT) became an option to further expand the organ donor pool. DLT utilizes the explanted liver of one liver transplant recipient as a donor graft in another patient. Despite being a surgically, and logistically demanding procedure, excellent results could be achieved in experienced high-volume transplant centers. In this review we present the current world status of DLT.

2020 - Development and Validation of a Comprehensive Model to Estimate Early Allograft Failure among Patients Requiring Early Liver Retransplant [Articolo su rivista]
Avolio, A. W.; Franco, A.; Schlegel, A.; Lai, Q.; Meli, S.; Burra, P.; Patrono, D.; Ravaioli, M.; Bassi, D.; Ferla, F.; Pagano, D.; Violi, P.; Camagni, S.; Dondossola, D.; Montalti, R.; Alrawashdeh, W.; Vitale, A.; Teofili, L.; Spoletini, G.; Magistri, P.; Bongini, M.; Rossi, M.; Mazzaferro, V.; Di Benedetto, F.; Hammond, J.; Vivarelli, M.; Agnes, S.; Colledan, M.; Carraro, A.; Cescon, M.; De Carlis, L.; Caccamo, L.; Gruttadauria, S.; Muiesan, P.; Cillo, U.; Romagnoli, R.; De Simone, P.
abstract

Importance: Expansion of donor acceptance criteria for liver transplant increased the risk for early allograft failure (EAF), and although EAF prediction is pivotal to optimize transplant outcomes, there is no consensus on specific EAF indicators or timing to evaluate EAF. Recently, the Liver Graft Assessment Following Transplantation (L-GrAFT) algorithm, based on aspartate transaminase, bilirubin, platelet, and international normalized ratio kinetics, was developed from a single-center database gathered from 2002 to 2015. Objective: To develop and validate a simplified comprehensive model estimating at day 10 after liver transplant the EAF risk at day 90 (the Early Allograft Failure Simplified Estimation [EASE] score) and, secondarily, to identify early those patients with unsustainable EAF risk who are suitable for retransplant. Design, Setting, and Participants: This multicenter cohort study was designed to develop a score capturing a continuum from normal graft function to nonfunction after transplant. Both parenchymal and vascular factors, which provide an indication to list for retransplant, were included among the EAF determinants. The L-GrAFT kinetic approach was adopted and modified with fewer data entries and novel variables. The population included 1609 patients in Italy for the derivation set and 538 patients in the UK for the validation set; all were patients who underwent transplant in 2016 and 2017. Main Outcomes and Measures: Early allograft failure was defined as graft failure (codified by retransplant or death) for any reason within 90 days after transplant. Results: At day 90 after transplant, the incidence of EAF was 110 of 1609 patients (6.8%) in the derivation set and 41 of 538 patients (7.6%) in the external validation set. Median (interquartile range) ages were 57 (51-62) years in the derivation data set and 56 (49-62) years in the validation data set. The EASE score was developed through 17 entries derived from 8 variables, including the Model for End-stage Liver Disease score, blood transfusion, early thrombosis of hepatic vessels, and kinetic parameters of transaminases, platelet count, and bilirubin. Donor parameters (age, donation after cardiac death, and machine perfusion) were not associated with EAF risk. Results were adjusted for transplant center volume. In receiver operating characteristic curve analyses, the EASE score outperformed L-GrAFT, Model for Early Allograft Function, Early Allograft Dysfunction, Eurotransplant Donor Risk Index, donor age × Model for End-stage Liver Disease, and Donor Risk Index scores, estimating day 90 EAF in 87% (95% CI, 83%-91%) of cases in both the derivation data set and the internal validation data set. Patients could be stratified in 5 classes, with those in the highest class exhibiting unsustainable EAF risk. Conclusions and Relevance: This study found that the developed EASE score reliably estimated EAF risk. Knowledge of contributing factors may help clinicians to mitigate risk factors and guide them through the challenging clinical decision to allocate patients to early liver retransplant. The EASE score may be used in translational research across transplant centers.

2020 - Efficient T cell compartment in HIV+ patients receiving orthotopic liver transplant and immunosuppressive therapy [Articolo su rivista]
Franceschini, Erica; De Biasi, Sara; Digaetano, Margherita; Bianchini, Elena; Lo Tartaro, Domenico; Gibellini, Lara; Menozzi, Marianna; Zona, Stefano; Tarantino, Giuseppe; Nasi, Milena; Codeluppi, Mauro; Guaraldi, Giovanni; Magistri, Paolo; Di Benedetto, Fabrizio; Pinti, Marcello; Mussini, Cristina; Cossarizza, Andrea
abstract

In patients undergoing orthotopic liver transplant (OLT), immunosuppressive (IS) treatment is mandatory and infections are leading causes of morbidity/mortality. Thus, it is essential to understand the functionality of cell-mediated immunity after OLT. The aim of the study was to identify changes in T cell phenotype and polyfunctionality in HIV+ and HIV- patients treated with IS after OLT.

2020 - First Case of Full Robotic ALPPS for Intrahepatic Cholangiocarcinoma [Articolo su rivista]
Di Benedetto, F.; Magistri, P.
abstract

Background: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) for intrahepatic cholangiocarcinoma (ICC) demonstrated good long-term outcomes1 and can increase the rate of resectability in locally advanced ICC;2 however, the rates of postoperative complications (Clavien–Dindo grade III) and mortality range between 13.6 and 44% and 0 and 29%, respectively.3 Minimally invasive strategies may reduce the risk of postoperative morbidity, with the same oncologic outcomes.4,5 We report the first case of full robotic ALPPS for advanced ICC. Methods: The patient was a 61-year-old male diagnosed with a 6.5 cm ICC involving segments IV, V, and VIII. The total clean liver volume was 1553 cc3, with a future liver remnant (FLR) volume of 21.6% (segments I, II, and III: 337 cc3). The procedure was performed by a senior hepato-pancreato-biliary (HPB) surgeon at the robotic console and a junior HPB surgeon at the table side. Results: Computed tomography scan on postoperative day (POD) 9 after stage 1 showed that FLR increased up to 38%. The indocyanine green clearance test showed a plasma disappearance rate of 19.8%/min and a retention rate at 15 min of 5.1%; complete blood tests are available at the end of the video. ALPPS was completed on POD 14, the postoperative course was uneventful, and the patient was discharged in good general condition on POD 5. Final pathology showed a 6 cm ICC, G3, R0 margin (10 mm), T2–N0–M0. The patient started adjuvant capecitabine, and after 6 months was in good general condition without signs of local or systemic recurrence. Conclusions: Robotic ALPPS combines the opportunity to perform a curative resection in patients presenting with insufficient FLR with the advantages of a minimally invasive approach. It is feasible and oncologically accurate for ICC when performed in fully trained HPB centers.

2020 - Full robotic ALPPS for HCC with intrahepatic portal vein thrombosis [Articolo su rivista]
Di Benedetto, F.; Assirati, G.; Magistri, P.
abstract

Background: The associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) technique can induce a greater degree of hypertrophy of the future liver remnant (FLR) in a shorter time compared with other procedures. A robotic approach may reduce the complication rate, increasing the ability to perform classic ALPPS. Methods: We report technical and clinical considerations on the first full robotic ALPPS (stages 1 and 2) for hepatocellular carcinoma (HCC) with portal vein intrahepatic tumor thrombus. Results: The patient was a 38-year-old man with Milan-out HCC and FLR volume of 19.6%. On postoperative day (POD) 8, FLR increased to 37%; therefore, he underwent completion of ALPPS on POD 10. The postoperative course was uneventful, and the patient was discharged in good general conditions on POD 3. Conclusion: Robotic ALPPS is safe and feasible for selected patients with initially unresectable HCC or requiring extended resections, with good postoperative outcomes.

2020 - Hepatocellular carcinoma and liver transplant: beyond the Milan criteria and the risk of "short-blanket" syndrome [Articolo su rivista]
Gitto, Stefano; Di Sandro, Stefano; Magistri, Paolo; Andreone, Pietro; Di Benedetto, Fabrizio
abstract

2020 - Laparoscopic versus open liver resection for intrahepatic cholangiocarcinoma: the first meta-analysis [Articolo su rivista]
Guerrini, G. P.; Esposito, G.; Tarantino, G.; Serra, V.; Olivieri, T.; Catellani, B.; Assirati, G.; Guidetti, C.; Ballarin, R.; Magistri, P.; Di Benedetto, F.
abstract

Background: Laparoscopic liver resection (LLR) has gained increasing acceptance for surgical treatment of malignant and benign liver tumors. LLR for intrahepatic cholangiocarcinoma (ICC) is not commonly performed because of the concern for the frequent need for major hepatectomy, vascular-biliary reconstructions, and lymph node dissection (LND). The aim of this present meta-analysis is to compare surgical and oncological outcomes of laparoscopic (LLR) versus open liver resection (OLR) for ICC. Materials and methods: A systematic review was conducted using the PubMed, MEDLINE, and Cochrane library database of published studies comparing LLR and OLR up to October 2019. Two reviewers independently assessed the eligibility and quality of the studies. Dichotomous data were calculated by odds ratio (OR), and continuous data were calculated by mean difference (MD) with 95% confidence intervals (95% CI). Results: Four retrospective observational studies describing 204 patients met the inclusion criteria. With respect to surgical outcomes, laparoscopic compared with open liver resection was associated with lower blood loss [MD − 173.86, (95% CI − 254.82, −92.91) p < 0.0001], less requirement of blood transfusion [OR 0.34, (95% CI 0.14, 0.82) p = 0.02], less need for Pringle maneuver [OR 0.17, (95% CI 0.07, 0.43) p = 0.0002], shorter hospital stay [MD − 3.77, (95% CI − 5.09, − 2.44; p < 0.0001], and less morbidity [OR 0.44, (95% CI 0.21, 0.94) p = 0.03]. With respect to oncological outcomes, the LLR group was prone to lower rates of lymphadenectomy [OR 0.12, (95% CI 0.06, 0.25) p < 0.0001], but surgical margins R0 and recurrence rate were not significantly different. Conclusion: Laparoscopic liver resection for ICC seems to achieve better surgical outcomes, providing short-term benefits without negatively affecting oncologic adequacy in terms of R0 resections and disease recurrence. However, a higher LND rate was observed in the open group. Due to the risk of bias and the statistical heterogeneity between the studies included in this review, further RCTs are needed to reach stronger scientific conclusions.

2020 - Left-sided portal hypertension after pancreatoduodenectomy with resection of the portal/superior mesenteric vein confluence. Results of a systematic review [Articolo su rivista]
Petrucciani, N.; Debs, T.; Rosso, E.; Addeo, P.; Antolino, L.; Magistri, P.; Gugenheim, J.; Ben Amor, I.; Aurello, P.; D'Angelo, F.; Nigri, G.; Di Benedetto, F.; Iannelli, A.; Ramacciato, G.
abstract

Background: Pancreatoduodenectomy with synchronous resection of the portal vein/superior mesenteric vein confluence may result in the development of left-sided portal hypertension. Left-sided portal hypertension presents with splenomegaly and varices and may cause severe gastrointestinal bleeding. The aim of the study is to review the incidence, treatment, and preventive strategies of left-sided portal hypertension. Methods: A systematic literature search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement to identify all studies published up to September 30, 2019 reporting data on patients with left-sided portal hypertension after pancreatoduodenectomy with venous resection. Results: Eight articles including 829 patients were retrieved. Left-sided portal hypertension occurred in 7.7% of patients who had splenic vein preservation and 29.4% of those having splenic vein ligation. Fourteen cases of gastrointestinal bleeding owing to left-sided portal hypertension were reported at a mean interval of 28 months from pancreatoduodenectomy. Related mortality at 1 month was 7.1%. Treatment of left-sided portal hypertension consisted of splenectomy in 3 cases (21%) and colectomy in 1 (7%) case, whereas radiologic, endoscopic procedures or conservative treatments were effective in the other cases (71%). Conclusion: Left-sided portal hypertension represents a potentially severe complication of pancreatoduodenectomy with venous resection occurring at greater incidence when the splenic vein is ligated and not reimplanted. Left-sided portal hypertension-related gastrointestinal bleeding although rare can be managed depending on the situation by endoscopic, radiologic procedures or operative intervention with low related mortality.

2020 - Liver resection in Cirrhotic liver: Are there any limits? [Articolo su rivista]
Chan, A.; Kow, A.; Hibi, T.; Di Benedetto, F.; Serrablo, A.
abstract

Liver resection remains one of the most technically challenging surgical procedure in abdominal surgery due to the complex anatomical arrangement in the liver and its rich blood supply that constitutes about 20% of the cardiac output per cycle. The challenge for resection in cirrhotic livers is even higher because of the impact of surgical stress and trauma imposed on borderline liver function and the impaired ability for liver regeneration in cirrhotic livers. Nonetheless, evolution and advancement in surgical techniques as well as knowledge in perioperative management of liver resection has led to a substantial improvement in surgical outcome in recent decade. The objective of this article was to provide updated information on the recent developments in liver surgery, from preoperative evaluation, to technicality of resection, future liver remnant augmentation and finally, postoperative management of complications.

2020 - Minimally Invasive Stage 1 to Protect against the Risk of Liver Failure: Results from the Hepatocellular Carcinoma Series of the Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy Italian Registry [Articolo su rivista]
Serenari, M.; Ratti, F.; Zanello, M.; Guglielmo, N.; Mocchegiani, F.; Di Benedetto, F.; Nardo, B.; Mazzaferro, V.; Cillo, U.; Massani, M.; Colledan, M.; Dalla Valle, R.; Cescon, M.; Vivarelli, M.; Colasanti, M.; Ettorre, G. M.; Aldrighetti, L.; Jovine, E.
abstract

Introduction: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has been described to treat hepatocellular carcinoma (HCC) but burdened, in its pioneering phase, by high morbidity and mortality. With the advent of minimally invasive (MI) techniques in liver surgery, surgical complications, including posthepatectomy liver failure (PHLF), have been dramatically reduced. The primary endpoint of this study was to compare the short-term outcomes of MI-versus open-ALPPS for HCC, with specific focus on PHLF. Methods: Data of patients submitted to ALPPS for HCC between 2012 and 2020 were identified from the ALPPS Italian Registry. Patients receiving an MI Stage 1 (MI-ALPPS) constituted the study group, whereas the patients who received an open Stage 1 (open-ALPPS) constituted the control group. Results: Sixty-six patients were enrolled from 12 Italian centers. Stage 1 of ALPPS was performed in 14 patients using an MI approach (21.2%). MI-ALPPS patients were discharged after Stage 1 at a significantly higher rate compared with open-ALPPS (78.6% versus 9.6%, P < .001). After Stage 2, major morbidity after MI-ALPPS was 8.3% compared with 28.6% reported after open-ALPPS. Mortality was nil after MI-ALPPS. Length of hospital stay was significantly shorter in MI-ALPPS (12 days versus 22 days, P < .001). Univariate logistic regression analysis (Firth method) found that both MI-ALPPS (odds ratio [OR] = 0.05, P = .040) and partial parenchymal transection (OR = 0.04, P = .027) were protective against PHLF. Conclusion: This national multicenter study showed that a less invasive approach to ALPPS first stage was associated with a lower overall risk of PHLF.

2020 - Multicentre evaluation of case volume in minimally invasive hepatectomy [Articolo su rivista]
Vigano, L.; Cimino, M.; Aldrighetti, L.; Ferrero, A.; Cillo, U.; Guglielmi, A.; Ettorre, G. M.; Giuliante, F.; Dalla Valle, R.; Mazzaferro, V.; Jovine, E.; De Carlis, L.; Calise, F.; Torzilli, G.; Ratti, F.; Gringeri, E.; Russolillo, N.; Levi Sandri, G. B.; Ardito, F.; Boggi, U.; Gruttadauria, S.; Di Benedetto, F.; Rossi, G. E.; Berti, S.; Ceccarelli, G.; Vincenti, L.; Belli, G.; Zamboni, F.; Coratti, A.; Mezzatesta, P.; Santambrogio, R.; Navarra, G.; Giuliani, A.; Pinna, A. D.; Parisi, A.; Colledan, M.; Slim, A.; Antonucci, A.; Grazi, G. L.; Frena, A.; Sgroi, G.; Brolese, A.; Morelli, L.; Floridi, A.; Patriti, A.; Veneroni, L.; Boni, L.; Maida, P.; Griseri, G.; Filauro, M.; Guerriero, S.; Tisone, G.; Romito, R.; Tedeschi, U.; Zimmitti, G.
abstract

Background: Surgical outcomes may be associated with hospital volume and the influence of volume on minimally invasive liver surgery (MILS) is not known. Methods: Patients entered into the prospective registry of the Italian Group of MILS from 2014 to 2018 were considered. Only centres with an accrual period of at least 12 months and stable MILS activity during the enrolment period were included. Case volume was defined by the mean number of minimally invasive liver resections performed per month (MILS/month). Results: A total of 2225 MILS operations were undertaken by 46 centres; nine centres performed more than two MILS/month (1376 patients) and 37 centres carried out two or fewer MILS/month (849 patients). The proportion of resections of anterolateral segments decreased with case volume, whereas that of major hepatectomies increased. Left lateral sectionectomies and resections of anterolateral segments had similar outcome in the two groups. Resections of posterosuperior segments and major hepatectomies had higher overall and severe morbidity rates in centres performing two or fewer MILS/month than in those undertaking a larger number (posterosuperior segments resections: overall morbidity 30·4 versus 18·7 per cent respectively, and severe morbidity 9·9 versus 4·0 per cent; left hepatectomy: 46 versus 22 per cent, and 19 versus 5 per cent; right hepatectomy: 42 versus 34 per cent, and 25 versus 15 per cent). Conclusion: A volume–outcome association existed for minimally invasive hepatectomy. Complex and major resections may be best managed in high-volume centres.

2020 - Perspectives from Italy during the COVID-19 pandemic: nationwide survey-based focus on minimally invasive HPB surgery [Articolo su rivista]
Aldrighetti, L.; Boggi, U.; Falconi, M.; Giuliante, F.; Cipriani, F.; Ratti, F.; Torzilli, G.; Abu Hilal, M.; Andrianello, S.; Anselmo, A.; Ardito, F.; Gian, L. B.; Banchini, F.; Barabino, M.; Barberis, A.; Bassi, C.; Batignani, G.; Battiston, C.; Belli, A.; Berti, S.; Bianco, P.; Brolese, A.; Brozzetti, S.; Butturini, G.; Calise, F.; Carabott, K.; Capretti, G.; Casadei, R.; Cescon, M.; Cesaretti, M.; Cillo, U.; Cinardi, N.; Colledan, M.; Coppola, A.; Cotsoglou, C.; Crippa, S.; Bona, E. D.; Valle, R. D.; De Angelis, M.; De Carlis, L.; Di Benedetto, F.; Di Sebastiano, P.; Dova, L.; Ercolani, G.; Esposito, A.; Giuseppe, M. E.; Fabris, A.; Ferrero, A.; Frena, A.; Frigerio, I.; Gianotti, L.; Giuliani, A.; Grazi, G.; Gringeri, E.; Griseri, G.; Gruttadauria, S.; Guglielmi, A.; Izzo, F.; Jovine, E.; Lanza, E.; Malleo, G.; Manzini, L.; Massani, M.; Mazzaferro, V.; Memeo, R.; Minni, F.; Morelli, L.; Nappo, G.; Nardo, B.; Orlando, F.; Partelli, S.; Patriti, A.; Patrone, R.; Percivale, A.; Piccolo, G.; Ravaioli, M.; Reggiani, P.; Risaliti, M.; Rocca, A.; Romagnoli, R.; Romano, F.; Russolillo, N.; Ruzzenente, A.; Saladino, E.; Salvia, R.; Santambrogio, R.; Tarchi, P.; Troci, A.; Troisi, R.; Urbani, L.; Veneroni, L.; Vennarecci, G.; Vigano, L.; Viola, M.; Vistoli, F.; Vivarelli, M.; Zanello, M.; Zanus, G.; Zerbi, A.
abstract

The safety of minimally invasive procedures during COVID pandemic remains hotly debated, especially in a country, like Italy, where minimally invasive techniques have progressively and pervasively entered clinical practice, in both the hepatobiliary and pancreatic community. A nationwide snapshot of the management of HPB minimally invasive surgery activity during COVID-19 pandemic is provided: a survey was developed and conducted within AICEP (Italian Association of HepatoBilioPancreatic Surgeons) with the final aim of conveying the experience, knowledge, and opinions into a unitary report enabling more efficient crisis management. Results from the survey (81 respondents) show that, in Italian hospitals, minimally invasive surgery maintains its role despite the COVID-19 pandemic, with the registered reduction of cases being proportional to the overall reduction of the HPB surgical activity. Respondents agree that the switch from minimally invasive to open technique can be considered as a valid option for cases with a high technical complexity. Several issues merit specific attention: screening for virus positivity should be universally performed; only expert surgical teams should operate on positive patients and specific technical measures to lower the biological risk of contamination during surgery must be followed. Future studies specifically designed to establish the true risks in minimally invasive surgery are suggested. Furthermore, a standard and univocal process of prioritization of patients from Regional Healthcare Systems is advisable.

2020 - Pre-transplant diabetes predicts atherosclerotic vascular events and cardiovascular mortality in liver transplant recipients: a long-term follow-up study [Articolo su rivista]
Gitto, S.; De Maria, N.; Marzi, L.; Magistri, P.; Falcini, M.; Vitale, G.; Olivieri, T.; Guerrini, G. P.; Serra, V.; Forte, P.; Carrai, P.; De Simone, P.; Mega, A.; Zoller, H.; Piai, G.; Schepis, F.; Marocchi, M.; Villa, E.; Marra, F.; Andreone, P.; Di Benedetto, F.; Vizzutti, F.; Laffi, G.; Borelli, E.; Ballarin, R.; Tarantino, G.; Di Sandro, S.; Puntili, R.; Petruccelli, S.; Valente, G.; Turco, L.
abstract

Background Early after surgery, liver transplant (LT) recipients often develop weight gain. Metabolic disorders and cardiovascular disease represent main drivers of morbidity and mortality. Our aim was to identify predictors of atherosclerotic vascular events (AVE) and to assess the impact of AVE on the long-term outcome. Methods We retrospectively analyzed data from patients transplanted between 2000 and 2005 and followed-up in five Italian transplant clinics. Cox Regression analysis was performed to identify predictors of AVE, global mortality, and cardiovascular mortality. Survival analysis was performed using the Kaplan-Meier method. Results We analyzed data from 367 subjects during a median follow-up of 14 years. Thirty-seven post-LT AVE were registered. Patients with AVE more frequently showed pre-LT diabetes mellitus (DM) (48.6 vs 13.9%, p=0.000). In the post-LT period, patients with AVE satisfied criteria of metabolic syndrome in 83.8% vs. 36.7% of subjects without AVE (p=0.000). At multivariate analysis, pre-LT DM independently predicted AVE (HR 2.250, CI 4.848-10.440, p=0.038). Moreover, both pre-LT DM and AVE strongly predicted cardiovascular mortality (HR 5.418, CI 1.060-29.183, p=0.049, and HR 86.097, CI 9.510-779.480, p=0.000, respectively). Conclusions Pre-LT DM is the main risk factor for post-LT AVE. Pre-LT DM and post-LT AVE are strong, long-term predictors of cardiovascular mortality. Patients with pre-LT DM should obtain a personalized follow-up for prevention or early diagnosis of AVE.

2020 - Pushing the limits in DCD donor selection: optimizing graft rehabilitation with ex vivo machine perfusion [Articolo su rivista]
Magistri, P.; Olivieri, T.; Guidetti, C.; Guerrini, G. P.; Agnoletti, V.; Muiesan, P.; Di Benedetto, F.
abstract

BACKGROUND: The use of liver grafts from donors after circulatory death (DCD) is associated with an increased risk of developing severe transplant-related complications. However, a balanced evaluation of risks calculated on both donor's and recipient's specific medical history, may reduce the incidence of post-operative complications avoiding a futile transplant. METHODS: We report a case wherein we transplanted a patient with hepatocellular carcinoma (HCC) outside Milan criteria using a borderline DCD graft. The decision to accept the offered DCD liver was difficult given the extent of injury from severe abdominal trauma, initial blood tests (AST 1782 U/I, ALT 1803 U/I, CPK 12931 mg/dl on procurement day) and technical complexity of Normothermic Regional Perfusion (NRP) due to the amputation of the left lower limb and multiple pelvic fractures. Liver biopsy showed 0% of macro-steatosis and 30% necrosis. We applied our standardized protocol of sequential NRP during graft procurement followed by D-HOPE machine perfusion prior implantation. RESULTS: The graft underwent 130 minutes of cold storage and 192 minutes of D-HOPE machine perfusion before being transplanted and total ischemia time was of 261 minutes. After eleven months, the patient is in good general conditions, no signs of HCC recurrence, AFP 2,7 ng/ml. CONCLUSIONS: The evaluation of the donor should always be based on both pre- and intra-procurement data, taking into-account lactate and transaminase trend during ECMO, liver perfusion and macroscopic appearance of the organ. The use of this grafts may result in a curative chance for patients that demonstrated a favorable HCC biology by pushing the limits of both organ and recipient selection.

2020 - Risk-adjusted benchmarks in laparoscopic liver surgery in a national cohort [Articolo su rivista]
Russolillo, N.; Aldrighetti, L.; Cillo, U.; Guglielmi, A.; Ettorre, G. M.; Giuliante, F.; Mazzaferro, V.; Dalla Valle, R.; De Carlis, L.; Jovine, E.; Ferrero, A.; Ratti, F.; Lo Tesoriere, R.; Gringeri, E.; Ruzzenente, A.; Levi Sandri, G. B.; Ardito, F.; Virdis, M.; Iaria, M.; Ferla, F.; Lombardi, R.; Di Benedetto, F.; Gruttadauria, S.; Boggi, U.; Torzilli, G.; Rossi, E.; Vincenti, L.; Berti, S.; Ceccarelli, G.; Belli, G.; Zamboni, F.; Calise, F.; Coratti, A.; Santambrogio, R.; Brolese, A.; Navarra, G.; Mezzatesta, P.; Zimmitti, G.; Ravaioli, M.
abstract

Background: This study aimed to assess the best achievable outcomes in laparoscopic liver resection (LLR) after risk adjustment based on surgical technical difficulty using a national registry. Methods: LLRs registered in the Italian Group of Minimally Invasive Liver Surgery registry from November 2014 to March 2018 were considered. Benchmarks were calculated according to the Achievable Benchmark of Care (ABC™). LLRs at each centre were divided into three clusters (groups I, II and III) based on the Kawaguchi classification. ABCs for overall and major morbidity were calculated in each cluster. Multivariable analysis was used to identify independent risk factors for overall and major morbidity. Significant variables were used in further risk adjustment. Results: A total of 1752 of 2263 patients fulfilled the inclusion criteria: 1096 (62·6 per cent) in group I, 435 (24·8 per cent) in group II and 221 (12·6 per cent) in group III. The ABCs for overall morbidity (7·8, 14·2 and 26·4 per cent for grades I, II and II respectively) and major morbidity (1·4, 2·2 and 5·7 per cent) increased with the difficulty of LLR. Multivariable analysis showed an increased risk of overall morbidity associated with multiple LLRs (odds ratio (OR) 1·35), simultaneous intestinal resection (OR 3·76) and cirrhosis (OR 1·83), and an increased risk of major morbidity with intestinal resection (OR 4·61). ABCs for overall and major morbidity were 14·4 and 3·2 per cent respectively for multiple LLRs, 30 and 11·1 per cent for intestinal resection, and 14·9 and 4·8 per cent for cirrhosis. Conclusion: Overall morbidity benchmarks for LLR ranged from 7·8 to 26·4 per cent, and those for major morbidity from 1·4 to 5·7 per cent, depending on complexity. Benchmark values should be adjusted according to multiple LLRs or simultaneous intestinal resection and cirrhosis.

2020 - Robotic liver resection: hurdles and beyond [Articolo su rivista]
Di Benedetto, Fabrizio; Petrowsky, Henrik; Magistri, Paolo; Halazun, Karim J
abstract

Laparoscopy is currently considered the standard of care for certain procedures such as left-lateral sectionectomies and wedge resections of anterior segments. The role of robotic liver surgery is still under debate, especially with regards to oncological outcomes. The purpose of this review is to describe how the field of robotic liver surgery has expanded, and to identify current limitations and future perspectives of the technology. Available evidences suggest that oncologic results after robotic liver resection are comparable to open and laparoscopic approaches for hepatocellular carcinoma and colorectal liver metastases, with identifiable advantages for cirrhotic patients and patients undergoing repeat resections. Excellent outcomes and optimal patient safety can be only achieved with specific hepato-biliary and general minimally invasive training to overcome the learning curve.

2020 - Robotic liver resection versus percutaneous ablation for early hcc: Short-and long-term results [Articolo su rivista]
Magistri, P.; Catellani, B.; Frassoni, S.; Guidetti, C.; Olivieri, T.; Assirati, G.; Caporali, C.; Pecchi, A.; Serra, V.; Ballarin, R.; Guerrini, G. P.; Bagnardi, V.; Di Sandro, S.; Di Benedetto, F.
abstract

Background: The correct approach for early hepatocellular carcinoma (HCC) is debatable, since multiple options are currently available. Percutaneous ablation (PA) is associated in some series to reduced morbidity compared to liver resection (LR); therefore, minimally invasive surgery may play a significant role in this setting. Methods: All consecutive patients treated by robotic liver resection (RLR) or PA between January 2014 and October 2019 for a newly diagnosed single HCC, less than 3 cm in size (very early/early stages according to the Barcelona Clinic Liver Cancer (BCLC)) on chronic liver disease or liver cirrhosis, were enrolled in this retrospective study. The aim of this study was to compare short-and long-term outcomes to define the best approach in this specific cohort. Results: 60 patients fulfilled the inclusion criteria: 24 RLR and 36 PA. The two populations were homogeneous in terms of baseline characteristics. There were no statistically significant differences regarding the incidence of postoperative morbidity (RLR 38% vs. PA 19%, p = 0.15). The cumulative incidence of recurrence (CIR) was significantly higher in patients who underwent PA, with the one, two, and three years of CIR being 42%, 69%, and 73% in the PA group and 17%, 27%, and 27% in the RLR group, respectively. Conclusions: RLR provides a significantly higher potential of cure and tumor-related free survival in cases of newly diagnosed single HCCs smaller than 3 cm. Therefore, it can be considered as a first-line approach for the treatment of patients with those characteristics in high-volume centers with extensive experience in the field of hepatobiliary surgery and minimally invasive approaches.

2020 - Robotic versus laparoscopic gastrectomy for gastric cancer: The largest meta-analysis [Articolo su rivista]
Guerrini, G. P.; Esposito, G.; Magistri, P.; Serra, V.; Guidetti, C.; Olivieri, T.; Catellani, B.; Assirati, G.; Ballarin, R.; Di Sandro, S.; Di Benedetto, F.
abstract

Background: Minimally invasive surgery (MIS) has been increasingly used in the treatment of gastric cancer (GC). Laparoscopic gastrectomy (LG) has shown several advantages over open surgery in dealing with GC, although it is still considered a demanding procedure. Robotic gastrectomy (RG) is now being employed with increased frequency worldwide and has been reported to overcome some limitations of conventional LG. The aim of this updated meta-analysis is to compare surgical and oncological outcomes of RG versus LG for gastric cancer. Materials and methods: A systematic review and meta-analysis was conducted using the PubMed, MEDLINE and Cochrane library database of published studies comparing RG and LG up to March 2020. The evaluated end-points were intra-operative, post-operative and oncological outcomes. Dichotomous data were calculated by odds ratio (OR) and continuous data were calculated by mean difference (MD) with 95% confidence intervals (95% CI), and a random-effect model was always applied. Results: Forty retrospective studies describing 17,712 patients met the inclusion criteria. With respect to surgical outcomes, robotic compared with laparoscopic gastrectomy was associated with higher operating time [MD 44.73, (95%CI 36.01, 53.45) p < 0.00001] and less intraoperative blood loss [MD -18.24, (95%CI -25.21, −11.26) p < 0.00001] and lower rate of surgical complication in terms of Dindo-Clavien ≥ 3 classification [OR 0.66, (95%CI 0.49, 0.88) p = 0.005]. With respect to oncological outcomes, the RG group showed a significantly increased mean number of retrieved lymph nodes [MD 1.84, (95%CI 0.84, 2.84) p = 0.0003], but mean proximal and distal resection margin distance and the recurrence rate were not significantly different between the two approaches. Conclusions: With respect to safety, technical feasibility and oncological adequacy, robotic and laparoscopic groups were comparable, although the robotic approach seems to achieve better short-term surgical outcomes. Moreover, a higher rate of retrieved lymph nodes was observed in the RG group.

2020 - Robotic vs open distal pancreatectomy: A multi-institutional matched comparison analysis [Articolo su rivista]
Magistri, P.; Boggi, U.; Esposito, A.; Carrano, F. M.; Pesi, B.; Ballarin, R.; De Pastena, M.; Menonna, F.; Moraldi, L.; Melis, M.; Coratti, A.; Newman, E.; Napoli, N.; Ramera, M.; Di Benedetto, F.
abstract

Background: Pancreatic surgery is still a challenge even in high-volume centers. Clinically relevant postoperative pancreatic fistula (CR-POPF) represents the greatest contributor to major morbidity and mortality, especially following pancreatic distal resection. In this study, we compared robotic distal pancreatectomy (RDP) to open distal pancreatectomy (ODP) in terms of CR-POPF development and analyzed oncologic efficacy of RDP in the subgroup of patients with pancreatic ductal adenocarcinoma (PDAC). Methods: We collected data from five high-volume centers for pancreatic surgery and performed a matched comparison analysis to compare short and long-term outcomes after ODP or RDP. Patients were matched with a 2:1 ratio according to age, ASA (American Society of Anesthesiologists) score, body mass index (BMI), final pathology, and TNM (Tumour, Node, Metastasis) staging system VIII ed. Results: Two hundred and forty-six patients who underwent 82 RDPs and 164 ODPs were included. No differences were found in the incidence of CR-POPF. In the PDAC group, median DFS and OS were 10.8 months and 14.8 months in the ODP group and 10.4 months and 15 months in the RDP group, respectively. Conclusions: Robotic distal pancreatectomy is a safe surgical strategy for PDAC and incidence of CR-POPF is equivalent between RDP and ODP. RDP should be considered equivalent to ODP in terms of oncological efficacy when performed in high-volume and proficient centers.

2020 - Temporal trends and outcomes in liver transplantation for recipients with HIV infection in Europe and United States [Articolo su rivista]
Campos-Varela, I.; Dodge, J. L.; Berenguer, M.; Adam, R.; Samuel, D.; Di Benedetto, F.; Karam, V.; Belli, L. S.; Duvoux, C.; Terrault, N. A.
abstract

Background. We evaluated trends and outcomes of liver transplantation (LT) recipients with/without HIV infection. Methods. LT recipients between 2008 and 2015 from the United Network for Organ Sharing and Organ Procurement and Transplantation Network and European Liver Transplant Registry were included. Trends and characteristics related to survival among LT recipients with HIV infection were determined. Results. Among 73 206 LT patients, 658 (0.9%) were HIV-infected. The proportion of LT HIV-infected did not change over time (P-trend = 0.16). Hepatitis C virus (HCV) as indication for LT decreased significantly for HIV-infected and HIV-uninfected patients (P-trends = 0.008 and <0.001). Three-year cumulative graft survival in LT recipients with and without HIV infection was 64.4% and 77.3%, respectively (P < 0.001), with improvements over time for both, but with HIV-infected patients having greater improvements (P-trends = 0.02 and 0.03). Adjusted risk of graft loss was 41% higher in HIV-infected versus HIV-uninfected (adjusted hazard ratio [aHR], 1.41; P < 0.001). Among HIV-infected, model of end-stage liver disease (aHR, 1.04; P < 0.001), body mass index <21 kg/m2(aHR, 1.61; P = 0.006), and HCV (aHR, 1.83; P < 0.001) were associated with graft loss, whereas more recent period of LT 2012-2015 (aHR, 0.58; P = 0.001) and donor with anoxic cause of death (aHR, 0.51; P = 0.007) were associated with lower risk of graft loss. Conclusions. Patients with HIV infection account for only 1% of LTs in United States and Europe, with fewer LT for HCV disease over time. A static rate of LT among HIV-infected patients may reflect improvements in cirrhosis management and/or persistent barriers to LT. Graft and patient survival among HIV-infected LT recipients have shown improvement over time.

2020 - The role of salvage transplantation in patients initially treated with open vs minimally invasive liver surgery: an intention-to-treat analysis [Articolo su rivista]
Levi Sandri, Giovanni B; Lai, Quirino; Ravaioli, Matteo; DI Sandro, Stefano; Balzano, Emanuele; Pagano, Duilio; Magistri, Paolo; DI Benedetto, Fabrizio; Rossi, Massimo; Gruttadauria, Salvatore; DE Simone, Paolo; Ettorre, Giuseppe M; DE Carlis, Luciano; Cescon, Matteo
abstract

Recently, minimally invasive liver surgery (MILS) has gained wide consensus in the management of hepatocellular carcinoma (HCC). However, its role in the setting of a salvage liver transplantation (SLT) has been poorly investigated. We analyzed the intention-to-treat survival of HCC patients treated with MILS vs. the open approach and eventually waitlisted for SLT. The secondary end-point was identification of risk factors for post-transplant death and tumor recurrence.

2019 - A national mandatory-split liver policy: A report from the Italian experience [Articolo su rivista]
Angelico, R.; Trapani, S.; Spada, M.; Colledan, M.; de Ville de Goyet, J.; Salizzoni, M.; De Carlis, L.; Andorno, E.; Gruttadauria, S.; Ettorre, G. M.; Cescon, M.; Rossi, G.; Risaliti, A.; Tisone, G.; Tedeschi, U.; Vivarelli, M.; Agnes, S.; De Simone, P.; Lupo, L. G.; Di Benedetto, F.; Santaniello, W.; Zamboni, F.; Mazzaferro, V.; Rossi, M.; Puoti, F.; Camagni, S.; Grimaldi, C.; Gringeri, E.; Rizzato, L.; Nanni Costa, A.; Cillo, U.
abstract

To implement split liver transplantation (SLT) a mandatory-split policy has been adopted in Italy since August 2015: donors aged 18-50 years at standard risk are offered for SLT, resulting in a left-lateral segment (LLS) graft for children and an extended-right graft (ERG) for adults. We aim to analyze the impact of the new mandatory-split policy on liver transplantation (LT)-waiting list and SLT outcomes, compared to old allocation policy. Between August 2015 and December 2016 out of 413 potentially “splittable” donors, 252 (61%) were proposed for SLT, of whom 53 (21%) donors were accepted for SLT whereas 101 (40.1%) were excluded because of donor characteristics and 98 (38.9%) for absence of suitable pediatric recipients. The SLT rate augmented from 6% to 8.4%. Children undergoing SLT increased from 49.3% to 65.8% (P =.009) and the pediatric LT-waiting list time dropped (229 [10-2121] vs 80 [12-2503] days [P =.045]). The pediatric (4.5% vs 2.5% [P =.398]) and adult (9.7% to 5.2% [P <.001]) LT-waiting list mortality reduced; SLT outcomes remained stable. Retransplantation (HR = 2.641, P =.035) and recipient weight >20 kg (HR = 5.113, P =.048) in LLS, and ischemic time >8 hours (HR = 2.475, P =.048) in ERG were identified as predictors of graft failure. A national mandatory-split policy maximizes the SLT donor resources, whose selection criteria can be safely expanded, providing favorable impact on the pediatric LT-waiting list and priority for adult sick LT candidates.

2019 - Chasing the right path: tips, tricks and challenges of robotic approach to posterior segments [Articolo su rivista]
Di Benedetto, Fabrizio; Tarantino, Giuseppe; Magistri, Paolo
abstract

2019 - Early post-liver transplant surgical morbidity in HIV-infected recipients: risk factor for overall survival? A nationwide retrospective study [Articolo su rivista]
Baccarani, U; Pravisani, R; Isola, M; Mocchegiani, F; Lauterio, A; Righi, E; Magistri, P; Corno, V; Adani, G; Lorenzin, D; Di Sandro, S; Pagano, D; Bassetti, M; Gruttadauria, S; De Carlis, L; Vivarelli, M; Di Benedetto, F; Risaliti, A.
abstract

The aim of the study was to analyse the risk factors for early surgical complications requiring relaparotomy and the related impact on overall survival (OS) in HIV-infected patients submitted to liver transplantation. Thus a retrospective investigation was conducted on a nationwide multicentre cohort of 157 HIV patients submitted to liver transplantation in six Italian Transplant Units between 2004 and 2014. An early relaparotomy was performed in 24.8% of cases and the underlying clinical causes were biliary leak (8.2%), bleeding (8.2%), intestinal perforation (4.5%) and suspect of vascular complications(3.8%). No differences in terms of prevalence for either overall or cause-specific early relaparotomies were noted when compared with a non-HIV control group, matched for MELD, recipient age, HCV-RNA positivity and HBV prevalence. While in the control group an early relaparotomy appeared a negative prognostic factor, such impact on OS was not noted in HIV recipients. Nonetheless increasing number of relaparotomies were associated with decreased survival. In multivariate analysis, preoperative refractory ascites and Roux-en-Y choledochojejunostomy reconstruction were significant risk factors for early relaparotomy. To conclude, in HIV liver transplanted patients, an increasing number of early relaparotomies because of surgical complications does negatively affect the OS. Preoperative refractory ascites reflecting a severe portal hypertension and a difficult biliary tract reconstruction requiring a Roux-en-Y choledochojejunostomy are associated with increased risk of early relaparotomy.

2019 - Efficacy and safety of Niuliva ® immune globulin to prevent hepatitis B reinfection in de novo orthotopic liver transplant [Articolo su rivista]
De Simone, P.; Salizzoni, M.; Cillo, U.; Di Benedetto, F.; Woodward, M. K.; Barcelo, M.; Paez, A.
abstract

Aims: To determine efficacy and safety of intravenous hepatitis B immune globulin (Niuliva ® , Grifols) to prevent reinfection in de novo orthotopic liver transplantation. Patients & methods: In a nonrandomized, noncontrolled and Phase III clinical trial, 15 adult patients (12 men) were treated with Niuliva from the anhepatic phase (10,000 IU/daily 1 week postsurgery) up to 6 or 12 months (5000 IU/weekly 1 month; 5000 IU/monthly thereafter). Results: No patients showed reinfection throughout the study. Niuliva was effective in maintaining antibody titers above the thresholds recommended by the European Medicines Agency (EMA) to prevent reinfection (100-150 IU/l). Four serious adverse events were reported in three patients (none related to the study product). There were no seroconversions and no deaths. Conclusion: Long-term, high-dose Niuliva administration was safe and effective to prevent graft reinfection in the tested patients.

2019 - Impact of a Multidisciplinary Team on Alcohol Recidivism and Survival After Liver Transplant for Alcoholic Disease [Articolo su rivista]
Magistri, P.; Marzi, L.; Guerzoni, S.; Vandelli, M.; Mereu, F.; Ascari, F.; Guidetti, C.; Tarantino, G.; Serra, V.; Guerrini, G. P.; Ballarin, R.; Moscara, M.; De Maria, N.; Villa, E.; Di Benedetto, F.
abstract

Background: Alcohol use disorders have a prevalence of 10% among the population of the United States and Europe and are one of the most frequent causes of liver cirrhosis in the Western world. Currently, alcohol-related liver cirrhosis represents one of the most frequent indications to liver transplant (LT), both as independent cause or associated with hepatitis C virus or hepatitis B virus infections. Starting from 2014, a multidisciplinary team involving surgeons, gastroenterologists, clinical toxicologists, psychiatrists, and psychologists was developed within the Modena Liver Transplant Center. Methods: We retrospectively reviewed our prospectively maintained institutional database of liver transplants in order to identify cirrhotic patients eligible for LT with a diagnosis of alcohol use disorder. Results: A total of 756 liver transplants were performed at Policlinico University Hospital, University of Modena, and Reggio Emilia, MO, Italy, between November 2000 and November 2017; 102 patients who underwent LT were considered eligible for inclusion in the study. Conclusions: The multidisciplinary approach, together with blood, urinary, and hair tests, allows identification of early recurrences and improves survival. Further studies are necessary to understand how multidisciplinary teams can change the 6-month rule in patient selection.

2019 - Improved Survival in Liver Transplant Patients Receiving Prolonged-release Tacrolimus-based Immunosuppression in the European Liver Transplant Registry (ELTR): An Extension Study [Articolo su rivista]
Adam, R.; Karam, V.; Cailliez, V.; Trunecka, P.; Samuel, D.; Tisone, G.; Nemec, P.; Soubrane, O.; Schneeberger, S.; Gridelli, B.; Bechstein, W. O.; Risaliti, A.; Line, P. -D.; Vivarelli, M.; Rossi, M.; Pirenne, J.; Klempnauer, J. L.; Rummo, A.; Di Benedetto, F.; Zieniewicz, K.; Troisi, R.; Paul, A.; Vali, T.; Kollmar, O.; Boudjema, K.; Hoti, E.; Colledan, M.; Pratschke, J.; Lang, H.; Popescu, I.; Ericzon, B. -G.; Strupas, K.; De Simone, P.; Kochs, E.; Heyd, B.; Gugenheim, J.; Pinna, A. D.; Bennet, W.; Kazimi, M.; Bachellier, P.; Wigmore, S. J.; Rasmussen, A.; Clavien, P. -A.; Hidalgo, E.; O'Grady, J. G.; Zamboni, F.; Kilic, M.; Duvoux, C.
abstract

BACKGROUND: We compared, through the European Liver Transplant Registry, long-term liver transplantation outcomes with prolonged-release tacrolimus (PR-T) versus immediate-release tacrolimus (IR-T)-based immunosuppression. This retrospective analysis comprises up to 8-year data collected between 2008 and 2016, in an extension of our previously published study. METHODS: Patients with <1 month follow-up were excluded; patients were propensity score matched for baseline characteristics. Efficacy measures included: univariate/multivariate analyses of risk factors influencing graft/patient survival up to 8 years posttransplantation, and graft/patient survival up to 4 years with PR-T versus IR-T. Overall, 13 088 patients were included from 44 European centers; propensity score-matched analyses comprised 3006 patients (PR-T: n = 1002; IR-T: n = 2004). RESULTS: In multivariate analyses, IR-T-based immunosuppression was associated with reduced graft survival (risk ratio, 1.49; P = 0.0038) and patient survival (risk ratio, 1.40; P = 0.0215). There was improvement with PR-T versus IR-T in graft survival (83% versus 77% at 4 y, respectively; P = 0.005) and patient survival (85% versus 80%; P = 0.017). Patients converted from IR-T to PR-T after 1 month had a higher graft survival rate than patients receiving IR-T at last follow-up (P < 0.001), or started and maintained on PR-T (P = 0.019). One graft loss in 4 years was avoided for every 14.3 patients treated with PR-T versus IR-T. CONCLUSIONS: PR-T-based immunosuppression might improve long-term outcomes in liver transplant recipients than IR-T-based immunosuppression.

2019 - Improving Outcomes Defending Patient Safety: The Learning Journey in Robotic Liver Resections [Articolo su rivista]
Magistri, P.; Guerrini, G. P.; Ballarin, R.; Assirati, G.; Tarantino, G.; Di Benedetto, F.
abstract

Background. While laparoscopy is currently adopted for hepatic resections, robotic approaches to the liver have not gained wide acceptance. We decided to analyze the learning curve in the field of robotic liver surgery comparing short-term outcomes between the first and the second half of our series. Methods. We retrospectively reviewed demographics and clinical data of patients who underwent robotic liver resection at our institution from July 2014 through September 2017. 60 patients diagnosed with primary or secondary liver neoplasms or hydatid disease were included in this study. ASA PS >3, heart failure, respiratory insufficiency, and general contraindication to pneumoperitoneum were exclusion criteria. Results. 60 patients were included. We observed a statistically significant decrease in operative time (p<0.001), intraoperative blood loss (p=0.01), and postoperative complications (p<0.001) after 30 cases. From the interpretation of the CUSUM curve, the time of operation appears to be significantly reduced after the first 30 operations. Discussion. This is the first European analysis of the learning curve for robotic liver resection in an HPB and liver transplant referral center. However, more studies are needed to confirm such results outside a HPB referral center. This is crucial to develop formal credentialing protocols for both junior and senior surgeons.

2019 - In vivo Bioluminescence-Based Monitoring of Liver Metastases from Colorectal Cancer: An Experimental Model [Articolo su rivista]
Magistri, Paolo; Battistelli, Cecilia; Toietta, Gabriele; Strippoli, Raffaele; Sagnotta, Andrea; Forgione, Antonello; Di Benedetto, Fabrizio; Uccini, Stefania; Vittorioso, Paola; D'Angelo, Francesco; Aurello, Paolo; Ramacciato, Giovanni; Nigri, Giuseppe
abstract

In this study we aimed to develop a new in vivo bioluminescence-based tool to monitor and to quantify colon cancer (CC) liver metastasis development.

2019 - Is It Possible a Conservative Approach After Radiochemotherapy in Locally Advanced Rectal Cancer (LARC)? A Systematic Review of the Literature and Meta-analysis [Articolo su rivista]
Fiorica, F.; Trovo, M.; Anania, G.; Marcello, D.; Di Benedetto, F.; Marzola, M.; D'Acapito, F.; Nasti, G.; Berretta, M.
abstract

Background: Locally advanced rectal cancer is usually treated with a preoperative approach with radiochemotherapy followed by surgery. Patients obtaining a pathologic complete response have a very favorable long-term prognosis. This study was intended to assess whether major surgery can reduce tumor recurrences and prolong survival of patients with a complete response after radiochemotherapy. Methods: Computerized literature search was performed to identify relevant articles. Comparative studies reporting the outcomes of non-operative and operative management in patients after neoadjuvant treatment were reviewed. Data synthesis was performed using Review Manager 5.0 software. Results: Twelve non-randomized comparative studies with a total of 1812 patients were suitable for analysis. There was no significant difference in overall survival at 3 and 5 years (odds ratio [OR] 1.31; 95% CI 0.64–2.69; p = 0.46 and 1.48; 95% CI 1.00–2.20; p = 0.50) and in disease-free survival at 3 and 5 years (odds ratio [OR] 1.20; 95% CI 0.68–2.14; p = 0.53 and 1.22; 95% CI 0.86–1.74; p = 0.26, respectively) between locally advanced rectal cancer patients treated with and without operative approach. Conclusions: Major surgery does not seem to improve prognosis in patients obtaining a complete response after radiochemotherapy. Clinical trials, using clear criteria to identify complete response patients, are needed to recommend non-operative approach.

2019 - Laparoscopic liver resection of hepatocellular carcinoma located in unfavorable segments: a propensity score-matched analysis from the I Go MILS (Italian Group of Minimally Invasive Liver Surgery) Registry [Articolo su rivista]
Levi Sandri, Giovanni Battista; Ettorre, Giuseppe Maria; Aldrighetti, Luca; Cillo, Umberto; Dalla Valle, Raffaele; Guglielmi, Alfredo; Mazzaferro, Vincenzo; Ferrero, Alessandro; Di Benedetto, Fabrizio; Gruttadauria, Salvatore; De Carlis, Luciano; Vennarecci, Giovanni; Antonucci, Adelmo; Belli, Giulio; Berti, Stefano; Boggi, Ugo; Bonsignore, Pasquale; Brolese, Alberto; Calise, Fulvio; Ceccarelli, Graziano; Colledan, Michele; Coratti, Andrea; Ferla, Fabio; Floridi, Antonio; Frena, Antonio; Giuliani, Antonio; Giuliante, Felice; Grazi, Gian Luca; Gringeri, Enrico; Griseri, Guido; Iaria, Maurizio; Jovine, Elio; Magistri, Paolo; Maida, Pietro; Mezzatesta, Pietro; Russolillo, Nadia; Navarra, Giuseppe; Parisi, Amilcare; Pinna, Antonio Daniele; Ratti, Francesca; Rossi, Giorgio Ettore; Ruzzenente, Andrea; Santambrogio, Roberto; Scotti, Andrea; Sgroi, Giovanni; Slim, Abdallah; Torzilli, Guido; Vincenti, Leonardo; Virdis, Matteo; Zamboni, Fausto
abstract

Objective: Laparoscopic liver resection (LLR) for Hepatocellular Carcinoma (HCC) is one of the most important indications for the minimally invasive approach. Our study aims to analyze the experience of the Italian Group of Minimally Invasive Liver Surgery with laparoscopic surgical treatment of HCC, with a focus on tumor location and how it affects morbidity and mortality. Methods: 38 centers participated in this study; 372 cases of LLR for HCC were prospectively enrolled. Patients were divided into two groups according to the HCC nodule location. Group 1 favorable location and group 2 unfavorable location. Perioperative outcomes were compared between the two groups before and after a propensity score match (PS) 1:1. Results: Before PS in group 2 surgical time was longer; conversion rate was higher; postoperative transfusion and comprehensive complication index were also higher. PS was performed with a cohort of 298 patients (from 18 centers), with 66 and 232 patients with HCC in unfavorable and favorable locations, respectively. After PS matching, 62 patients from group 1 and group 2 each were compared. Operative and postoperative course were similar in patients with HCC in favorable and unfavorable LLR locations. Surgical margins were found to be identical before and after PS. Conclusions: These results show that LLR in patients with HCC can be safely performed in all segments because of the extensive experience of all surgeons from multiple centers in performing traditional open liver surgery as well as laparoscopic surgery.

2019 - Not just minor resections: robotic approach for cystic echinococcosis of the liver [Articolo su rivista]
Magistri, P.; Pecchi, A.; Franceschini, E.; Pesi, B.; Guadagni, S.; Catellani, B.; Assirati, G.; Guidetti, C.; Guerrini, G. P.; Tarantino, G.; Ballarin, R.; Codeluppi, M.; Morelli, L.; Coratti, A.; Di Benedetto, F.
abstract

Introduction: Human echinococcosis is among the 17 neglected tropical diseases recognized by the World Health Organization. It is responsible for over $3 billion of health costs every year being endemic in large areas worldwide, and liver is affected in 70% of the cases. Surgery associated to medical treatment is the gold standard and robotic approach may be a valuable tool to achieve safe, parenchyma sparing resections. Methods: We retrospectively analyzed the outcomes of patients that underwent robotic radical surgical treatment for hydatid liver disease, from prospectively maintained databases of three Italian centers. Results: 15 patients were included in this study, median age 51 years (24–76). 1 right hepatectomy, 2 left lateral sectionectomies, 5 segmentectomies (including 1 caudatectomy), 3 wedge resections and 5 cyst-pericystectomies were performed. Median estimated blood loss was of 100 ml (50–550 ml), and median operative time including docking was 210 min (95–590 min), with no need for conversion to open. Median hospital stay was 4 days, with only one readmission for fever. Only one patient experienced recurrence in a different liver segment. Conclusions: In our experience, robotic approach for cystic echinococcosis of the liver proved to be a safe and effective strategy also in the so-called “difficult segments”, with short post-operative stay and quick return to daily activities, along with the absence of surgical site recurrences. To the best of our knowledge, this is the largest report of robotic approach to hydatid liver disease.

2019 - Robotic distal pancreatectomy: can results overcome cost-effectiveness prejudices? [Articolo su rivista]
Di Benedetto, Fabrizio; Ballarin, Roberto; Magistri, Paolo
abstract

2019 - Robotic Liver Resection Expands the Opportunities of Bridging Before Liver Transplantation [Articolo su rivista]
Magistri, P.; Olivieri, T.; Assirati, G.; Guerrini, G. P.; Ballarin, R.; Tarantino, G.; Di Benedetto, F.
abstract

2019 - Robotic liver resection for hepatocellular carcinoma: A systematic review [Articolo su rivista]
Magistri, P.; Tarantino, G.; Assirati, G.; Olivieri, T.; Catellani, B.; Guerrini, G. P.; Ballarin, R.; Di Benedetto, F.
abstract

Background: Hepatocellular carcinoma (HCC) represents a leading cause of death in patients with cirrhosis. This review attempts to clarify the role of robotic surgery for HCC in terms of oncologic outcomes. Materials and methods: A systematic literature search was performed according to the PRISMA statement including papers comparing open, robotic, and laparoscopic approach for liver surgery. If more than one study was reported by the same institute, only the most recent or the highest quality study was included. Results: The literature search yielded 302 articles; titles and abstracts were reviewed for inclusion. Ten papers were finally included in this review for a total of 307 patients who underwent robotic resection for HCC. Conclusions: Robotic liver resection for HCC is effective in terms of oncological results as compared with open and laparoscopic approach when performed in experienced centers and is accurate in terms of R0 rates and disease-free surgical margin.

2019 - Surgical Complications Requiring an Early Relaparotomy in HIV-Infected Liver Transplant Recipients: Risk Factors and Impact on Survival [Articolo su rivista]
Pravisani, R.; Baccarani, U.; Isola, M.; Mocchegiani, F.; Lauterio, A.; Righi, E.; Magistri, P.; Corno, V.; Adani, G. L.; Lorenzin, D.; Di Sandro, S.; Pagano, D.; Bassetti, M.; Gruttadauria, S.; De Carlis, L.; Vivarelli, M.; Di Benedetto, F.; Risaliti, A.
abstract

Aim: We aimed to analyze the risk factors for early surgical complications requiring relaparotomy and the related impact on overall survival (OS) in HIV-infected patients submitted to liver transplantation. Methods: We performed a retrospective study on a nationwide multicenter cohort of 157 HIV-infected patients submitted to liver transplantation in 6 Italian transplant units between 2004 to 2014. Results: The median preoperative model for end-stage liver disease score was 18 (interquartile range 12-26.5). An early relaparotomy was performed in 24.8% of patients, and the underlying clinical causes were biliary leak (8.2%), bleeding (8.2%), intestinal perforation (4.5%), and suspected vascular complications (3.8%). The OS at 1, 3, and 5 years was 74.3%, 68.0%, and 60.0%, respectively, and an early relaparotomy was not a prognostic factor itself, but an increasing number of relaparotomies was associated with decreased survival (hazard ratio = 1.40, 95% confidence interval [CI] 1.07-1.81, P = .01). In the multivariate analysis, preoperative refractory ascites (odds ratio 3.32, 95% CI 1.18-6.47, P = .02) and Roux-en-Y choledochojejunostomy reconstruction (odds ratio 12.712, 95% CI 2.47-65.38, P ≤ .01) were identified as significant risk factors for early relaparotomy. Conclusions: In HIV-infected liver transplant recipients, an increasing number of early relaparotomies due to surgical complications did negatively affect the OS. Preoperative refractory ascites reflecting a severe portal hypertension and a difficult biliary tract reconstruction requiring a Roux-en-Y choledochojejunostomy were associated with an increased risk of early relaparotomy.

2019 - Ultrasound-Guided Robotic Enucleation of Pancreatic Neuroendocrine Tumors [Articolo su rivista]
Di Benedetto, F; Magistri, P; Ballarin, R; Tarantino, G; Bartolini, I; Bencini, L; Moraldi, L; Annecchiarico, M; Guerra, F; Coratti, A
abstract

Background. Pancreatic neuroendocrine tumors (PanNETs) are relatively rare neoplasms with a low to mild malignant potential. They can be further divided into functioning and nonfunctioning, according to their secretive activity. Surgery is an optimal approach, but the classic open approach is challenging, with some patients having long hospitalization and potentially life-threatening complications. The robotic approach for PanNETs may represent an option to optimize their management. Methods. We retrospectively reviewed our prospectively maintained databases from 2 high-volume Italian centers for pancreatic surgery. Demographics, pathological characteristics, perioperative outcome, and medium-term follow-up of patients who underwent robotic pancreatic enucleations were collected. Results. Twelve patients with final diagnosis of PanNET were included. The mean age of the patients was 53.8 years (25-77). The median body mass index was 26 (24-29). Three lesions were functioning insulinomas, while the others were nonfunctioning tumors. No deaths occurred. Mild postoperative complications occurred, except for 1 grade B pancreatic fistula. The mean postoperative stay was 3.9 days (2-5). Conclusions. Our results confirm that robotic enucleation is a feasible and safe approach for the treatment of PanNETs, with short hospital stay and low incidence of morbidity.

2019 - University of Modena Experience With Liver Grafts From Donation After Circulatory Death: What Really Matters in Organ Selection? [Articolo su rivista]
Olivieri, T.; Magistri, P.; Guidetti, C.; Baroni, S.; Rinaldi, S.; Assirati, G.; Catellani, B.; Chierego, G.; Cantaroni, C.; Bondi, F.; Campagna, A.; Sangiorgi, G.; Pecchi, A.; Serra, V.; Tarantino, G.; Ballarin, R.; Guerrini, G. P.; Girardis, M.; Bertellini, E.; Di Benedetto, F.
abstract

Introduction: The use of grafts from donation after circulatory death (DCD) is an important additional source to implement within the donor pool. We herein report the outcomes of our early experience with DCD grafts for liver transplantation (LT). Methods: Ten patients successfully underwent LT with grafts from DCD donors between August 2017 and January 2019 at the Hepato-Pancreato-Biliary Surgery and Liver Transplant Unit of University of Modena and Reggio Emilia. All donors underwent normothermic regional perfusion after death declaration and, after the procurement, all the suitable grafts underwent ex situ hypothermic perfusion prior to transplantation. Results: Mean postoperative hospital stay after transplant was 12.7 days (range, 5-26), and in 5 cases we placed a biliary drainage (Kehr tube) during surgery. Primary graft nonfunction did not occur after LT in this cohort, although, we registered one case of biliary anastomosis stricture that was managed endoscopically by endoscopic retrograde cholangiopancreatography. All patients are alive and none required retransplantation. Conclusions: In our experience with controlled DCD donors, the demonstration of: (1) a negative trend of lactate during normothermic regional perfusion; (2) an aspartate aminotransferase and alanine aminotransferase level lower than 2000 mU/dL; and (3) less than 1 hour of functional warm ischemia time along with no signs of microscopic or macroscopic ischemia of the grafts, are related to positive outcomes in the first year after transplant. A DCD risk score based on Italian population characteristics and regulations on death observation may improve donor-recipient match and avoid futile transplants.

2019 - Vacuum-assisted management of surgical site infections after liver transplantation: 15-year experience in a tertiary hepatobiliary center [Articolo su rivista]
Magistri, P.; Olivieri, T.; Serra, V.; Tarantino, G.; Assirati, G.; Pecchi, A.; Ballarin, R.; Di Benedetto, F.
abstract

Immune compromised as well as critically ill patients are at higher risk of surgical wound infection and dehiscence. Wound infections critically influence the outcomes after liver transplantation. In particular, it was shown that they significantly reduce the overall survival rate when compared to patients with uneventful wound healing, and their occurrence is associated with death or graft loss within 1-year post-transplantation. From January 2001 through December 2017, 763 patients underwent liver transplantation in our Institution, the Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, "Policlinico" University Hospital, University of Modena and Reggio Emilia, Modena, Italy. We retrospectively analyzed data from our prospectively maintained database of patients treated with a negative pressure therapy device due to wound or abdominal infections. 13 patients underwent negative pressure treatments for surgical site infection after liver transplantation in our institution. Ten superficial "supra-fascial" applications (SF group) and three deeper abdominal (Ab group) were reported. Mean in-hospital stay for the SF group was 42.6 days, ranging from 8 to 80, while for the Ab group was 62 days (range 23-133), with an overall survival of 34 and 4.6 months, respectively. A multifactorial multidisciplinary approach is needed in the prevention of surgical site infections instead of mere antimicrobial prophylaxis The application of negative pressure wound therapy may help in controlling the diffusion of the infection and preventing sepsis.

2018 - Correction to: Diffusion, outcomes and implementation of minimally invasive liver surgery: a snapshot from the I Go MILS (Italian Group of Minimally Invasive Liver Surgery) Registry (Updates in Surgery, (2017), 69, 3, (271-283), 10.1007/s13304-017-0489-x) [Articolo su rivista]
Aldrighetti, L.; Ratti, F.; Cillo, U.; Ferrero, A.; Ettorre, G. M.; Guglielmi, A.; Giuliante, F.; Calise, F.; Dalla Valle, R.; Mazzaferro, V.; Jovine, E.; De Carlis, L. G.; Boggi, U.; Gruttadauria, S.; Di Benedetto, F.; Reggiani, P.; Berti, S.; Ceccarelli, G.; Vincenti, L.; Belli, G.; Torzilli, G.; Zamboni, F.; Coratti, A.; Mezzatesta, P.; Santambrogio, R.; Navarra, G.; Giuliani, A.; Pinna, A. D.; Parisi, A.; Colledan, M.; Slim, A.; Antonucci, A.; Grazi, G. L.; Frena, A.; Sgroi, G.; Brolese, A.; Morelli, L.; Floridi, A.; Patriti, A.; Veneroni, L.; Ercolani, G.; Boni, L.; Maida, P.; Griseri, G.; Percivale, A.; Filauro, M.; Guerriero, S.; Tisone, G.; Romito, R.; Tedeschi, U.; Zimmitti, G.
abstract

A technical error led to incorrect rendering of the author group in this article. The correct authorship is as follows: Luca Aldrighetti, Francesca Ratti, Umberto Cillo, Alessandro Ferrero, Giuseppe Maria Ettorre, Alfredo Guglielmi, Felice Giuliante, Fulvio Calise on behalf of the Italian Group of Minimally Invasive Liver Surgery (I GO MILS) The collaborators are: Raffaele Dalla Valle, AOU Parma, Parma; Vincenzo Mazzaferro, Istituto Nazionale Tumori, Milano; Elio Jovine, Ospedale Maggiore, Bologna; Luciano Gregorio De Carlis, Ospedale Niguarda Ca’ Granda, Milano; Ugo Boggi, AOU Pisana, Pisa; Salvatore Gruttadauria, ISMETT, Palermo; Fabrizio Di Benedetto, AOU Policlinico di Modena, Modena; Paolo Reggiani, Ospedale Maggiore Policlinico, Milano; Stefano Berti, Ospedale Civile S.Andrea, La Spezia; Graziano Ceccarelli, Ospedale San Donato, Arezzo; Leonardo Vincenti, AOU Consorziale Policlinico, Bari; Giulio Belli, Ospedale SM Loreto Nuovo, Napoli; Guido Torzilli, Istituto Clinico Humanitas, Rozzano; Fausto Zamboni, Ospedale Brotzu, Cagliari; Andrea Coratti, AOU Careggi, Firenze; Pietro Mezzatesta, Casa di Cura La Maddalena, Palermo; Roberto Santambrogio, AO San Paolo, Milano; Giuseppe Navarra, AOU Policlinico G. Martino, Messina; Antonio Giuliani, AO R.N. Cardarelli, Napoli; Antonio Daniele Pinna, Policlinico Sant’Orsola Malpighi, Bologna; Amilcare Parisi, AO Santa Maria di Terni, Terni; Michele Colledan, AO Papa Giovanni XXIII, Bergamo; Abdallah Slim, AO Desio e Vimercate, Vimercate; Adelmo Antonucci, Policlinico di Monza, Monza; Gian Luca Grazi, Istituto Nazionale Tumori Regina Elena, Roma; Antonio Frena, Ospedale Centrale, Bolzano; Giovanni Sgroi, AO Treviglio-Caravaggio, Treviglio; Alberto Brolese, Ospedale S.Chiara, Trento; Luca Morelli, AOU Pisana, Pisa; Antonio Floridi, AO Ospedale Maggiore, Crema; Alberto Patriti, Ospedale San Matteo degli Infermi, Spoleto; Luigi Veneroni, Ospedale Infermi AUSL Romagna, Rimini; Giorgio Ercolani, Ospedale Morgagni Pierantoni, Forlì; Luigi Boni, AOU Fondazione Macchi, Varese; Pietro Maida, Ospedale Villa Betania, Napoli; Guido Griseri, Ospedale San Paolo, Savona; Andrea Percivale, Ospedale Santa Corona, Pietraligure; Marco Filauro, AO Galliera, Genova; Silvio Guerriero, Ospedale San Martino, Belluno; Giuseppe Tisone, Policlinico Tor Vergata, Roma; Raffaele Romito, AOU Maggiore della Carità, Novara; Umberto Tedeschi, AOU Integrata Verona, Verona; Giuseppe Zimmitti, Fondazione Poliambulanza, Brescia.

2018 - De-novo nonalcoholic steatohepatitis is associated with long-term increased mortality in liver transplant recipients [Articolo su rivista]
Gitto, Stefano; de Maria, Nicola; di Benedetto, Fabrizio; Tarantino, Giuseppe; Serra, Valentina; Maroni, Lorenzo; Cescon, Matteo; Pinna, Antonio D; Schepis, Filippo; Andreone, Pietro; Villa, Erica
abstract

Patients who have undergone transplantation often develop metabolic syndrome (MetS) and de-novo nonalcoholic fatty liver disease (NAFLD). Our aim was to evaluate the impact of metabolic disease on cardiovascular and neoplastic risk and survival.

2018 - Extra-Anatomic Jump Graft from the Right Colic Vein: A Novel Technique to Manage Portal Vein Thrombosis in Liver Transplantation [Articolo su rivista]
Magistri, Paolo; Tarantino, Giuseppe; Olivieri, Tiziana; Pecchi, Annarita; Ballarin, Roberto; Di Benedetto, Fabrizio
abstract

In the context of cirrhosis, portal vein thrombosis (PVT) is present in 2.1% to 26% of patients. PVT is no longer considered an absolute contraindication for liver transplantation, and nowadays, surgical strategies depend on the extent of PVT. Complete PVT is associated with higher morbidity rates and poor prognosis, while comparable long-term outcomes can be achieved as long as physiological portal inflow is restored.

2018 - Gastric Mucormycosis in a Liver and Kidney Transplant Recipient: Case Report and Concise Review of Literature [Articolo su rivista]
Alfano, G.; Fontana, F.; Francesca, D.; Assirati, Giacomo; Magistri, P.; Tarantino, G.; Ballarin, R.; Rossi, G.; Franceschini, E.; Codeluppi, M.; Guaraldi, G.; Mussini, C.; Di Benedetto, F.; Cappelli, G.
abstract

Mucormycosis is an uncommonly encountered fungal infection in solid organ transplantation. The infection is severe and often results in a fatal outcome. The most common presentations are rhino-sino-orbital and pulmonary disease. We describe a rare case of gastric mucormycosis in a patient with a combined liver-kidney transplant affected by glycogen storage disease type Ia. A 42-year-old female patient presented with gastric pain and melena 26 days after transplantation. Evaluation with upper endoscopy showed two bleeding gastric ulcers. Histological examination of gastric specimens revealed fungal hyphae with evidence of Mucormycetes at subsequent molecular analysis. Immunosuppressive therapy was reduced and antifungal therapy consisting of liposomal amphotericin B and posaconazole was promptly introduced. Gastrointestinal side effects of posaconazole and acute T-cell rejection of renal graft complicated further management of the case. A prolonged course of daily injections of amphotericin B together with a slight increase of immunosuppression favored successful treatment of mucormycosis as well as of graft rejection. After 2-year follow-up examination, the woman was found to have maintained normal renal and liver function tests. We conclude that judicious personalization of antimicrobial and antirejection therapy should be considered to resolve every life-threatening case of mucormycosis in solid organ transplantation.

2018 - Laparoscopic pancreaticoduodenectomy for tumors of the head of the pancreas; 10 cases for a single center experience [Articolo su rivista]
Ballarin, R; Magistri, P; Tarantino, G; Assirati, G; Pecchi, A; Guerrini, Gp; Di Benedetto, F
abstract

We read with great interest the article by Caruso et al1 regarding their experience in a series of 10 patients undergoing laparoscopic pancreaticoduodenectomy (LPD) for a tumor in the head of the pancreas. The authors reported their single-center experience in this field so far, focusing on outcomes compared with open pancreaticoduodenectomy (PD).

2018 - Liver Angiopoietin-2 is a key predictor of de novo or recurrent hepatocellular cancer after HCV direct-acting antivirals [Articolo su rivista]
Faillaci, Francesca; Marzi, Luca; Critelli, Rosina; Milosa, Fabiola; Schepis, Filippo; Turola, Elena; Andreani, Silvia; Vandelli, Gabriele; Bernabucci, Veronica; Lei, Barbara; D'Ambrosio, Federica; Bristot, Laura; Cavalletto, Luisa; Chemello, Liliana; Sighinolfi, Pamela; Manni, Paola; Maiorana, Antonino; Caporali, Cristian; Bianchini, Marcello; Marsico, Maria; Turco, Laura; de Maria, Nicola; Del Buono, Mariagrazia; Todesca, Paola; di Lena, Luca; Romagnoli, Dante; Magistri, Paolo; di Benedetto, Fabrizio; Bruno, Savino; Taliani, Gloria; Giannelli, Gianluigi; Martinez-Chantar, Maria-Luz; Villa, Erica
abstract

Recent reports suggested that direct acting antivirals (DAAs) might favor hepatocellular carcinoma (HCC).In Study 1,we studied the proangiogenic liver microenvironment in 242 DAAs-treated chronic Hepatitis C patients with advanced fibrosis.Angiopoietin-2 expression was studied in tissue (cirrhotic and/or neoplastic) from recurrent,de novo,non-recurrent HCC or patients never developing HCC.Circulating Angiopoietin-2,vascular-endothelial growth factor (VEGF),and C-reactive protein were also measured. In Study 2,we searched for factors associated with de novo HCC in 257 patients with cirrhosis of different etiologies enrolled in a dedicated prospective study. Thorough biochemical,clinical,hemodynamic,endoscopic, elastographic,and echo-Doppler work-up was performed in both studies.In Study 1,none without cirrhosis developed HCC.Of 183 patients with cirrhosis,14/28 (50.0%) with previous HCC recurred while 21/155 (13.5%) developed de novo HCC.Recurrent and de novo HCCs had significantly higher liver fibrosis scores,portal pressure,and systemic inflammation than non-recurrent HCC or patients never developing HCC. In recurrent/de novo HCC patients,tumor and non-tumor Angiopoietin-2 showed an inverse relationship with portal vein velocity (r=-0.412,p=0.037 and r= -0.409,p=0.047,respectively) and a positive relationship with liver stiffness (r=0.526,p=0.007;r=0.525,p=0.003,respectively).Baseline circulating VEGF and cirrhotic liver Angiopoietin-2 were significantly related (r=0.414,p=0.044).VEGF increased during DAAs, remaining stably elevated at 3 months follow-up, when it significantly related with serum Angiopoietin-2 (r=0.531,p=0.005).Angiopoietin-2 expression in the primary tumor or in cirrhotic tissue before DAAs was independently related with the risk of HCC recurrence (OR 1.137,95%CI 1.044-1.137,p=0.003) or occurrence (OR 1.604,95% CI 1.080-2.382;p=0.019).In Study 2,DAA treatment (OR 4.770,95%CI 1.395-16.316,p=0.013) and large varices (OR 3.857,95%CI 1.127-13.203,p=0.032) were independent predictors of de novo HCC.

2018 - Under-dilated TIPS Associate With Efficacy and Reduced Encephalopathy in a Prospective, Non-randomized Study of Patients With Cirrhosis [Articolo su rivista]
Schepis, Filippo; Vizzutti, Francesco; Garcia-Tsao, Guadalupe; Marzocchi, Guido; Rega, Luigi; De Maria, Nicola; Di Maira, Tommaso; Gitto, Stefano; Caporali, Cristian; Colopi, Stefano; De Santis, Mario; Arena, Umberto; Rampoldi, Antonio; Airoldi, Aldo; Cannavale, Alessandro; Fanelli, Fabrizio; Mosconi, Cristina; Renzulli, Matteo; Agazzi, Roberto; Nani, Roberto; Quaretti, Pietro; Fiorina, Ilaria; Moramarco, Lorenzo; Miraglia, Roberto; Luca, Angelo; Bruno, Raffaele; Fagiuoli, Stefano; Golfieri, Rita; Torricelli, Pietro; Di Benedetto, Fabrizio; Saverio Belli, Luca; Banchelli, Federico; Laffi, Giacomo; Marra, Fabio; Villa, Erica
abstract

Portosystemic encephalopathy (PSE) is a major complication of trans-jugular intrahepatic porto-systemic shunt (TIPS) placement. Most devices are self-expandable polytetrafluoroethylene-covered stent grafts (PTFE-SGs) that are dilated to their nominal diameter (8 or 10 mm). We investigated whether PTFE-SGs dilated to a smaller caliber (under-dilated TIPS) reduce PSE yet maintain clinical and hemodynamic efficacy. We also studied whether under-dilated TIPS self-expand to nominal diameter over time. METHODS: We performed a prospective, non-randomized study of 42 unselected patients with cirrhosis who received under-dilated TIPS (7 and 6 mm) and 53 patients who received PTFE-SGs of 8 mm or more (controls) at referral centers in Italy. After completion of this study, dilation to 6 mm became the standard and 47 patients were included in a validation study. All patients were followed for 6 months; Doppler ultrasonography was performed 2 weeks and 3 months after TIPS placement and every 6 months thereafter. Stability of PTFE-SG diameter was evaluated by computed tomography analysis of 226 patients with cirrhosis whose stent grafts increased to 6, 7, 8, 9, or 10 mm. The primary outcomes were incidence of at least 1 episode of PSE grade 2 or higher during follow up, incidence of recurrent variceal hemorrhage or ascites (based on need for at least 1 large-volume paracentesis by 4 weeks after TIPS placement), incidence of shunt dysfunction requiring TIPS recanalization, and reduction in porto-caval pressure gradient. RESULTS: PSE developed in a significantly lower proportion of patients with under-dilated TIPS (46%) than controls (73%) during the first year after the procedure (P=.015), but the proportions of patients with recurrent variceal hemorrhage or ascites did not differ significantly between groups. No TIPS occlusions were observed. These results were confirmed in the validation cohort. In an analysis of self-expansion of stent grafts, during a mean follow-up period of 252 days after placement, none of the PTFE-SGs self-expanded to the nominal diameter in hemodynamically relevant sites (such as portal and hepatic vein vascular walls). CONCLUSION: In prospective, non-randomized study of patients with cirrhosis, we found under-dilation of PTFE-SGs during TIPS placement to be feasible, associated with lower rates of PSE, and effective

2018 - Use of robotics in liver donor right hepatectomy [Articolo su rivista]
Di Benedetto, F; Magistri, P; Halazun, Kj
abstract

We read with great interest the paper by Chen and colleagues entitled “Use of robotics in liver donor right hepatectomy” (1). The authors currently represent the leading group performing robotic living donor liver procurements with 15 procedures completed to date (2). Here they provide a review of the current literature demonstrating that robotic procurement of grafts for liver transplantation from living donors is a possible alternative to open and/or laparoscopic/hybrid approaches

2017 - A frailty index predicts post-liver transplant morbidity and mortality in HIV-positive patients [Articolo su rivista]
Guaraldi, Giovanni; Dolci, Giovanni; Zona, Stefano; Tarantino, Giuseppe; Serra, Valentina; Ballarin, Roberto; Franceschini, Erica; Codeluppi, Mauro; Brothers, Thomas D.; Mussini, Cristina; DI BENEDETTO, Fabrizio
abstract

Background: We hypothesized that frailty acts as a measure of health outcomes in the context of LT. The aim of this study was to explore frailty index across LT, as a measure of morbidity and mortality. This was a retrospective observational study including all consecutive 47 HIV+patients who received LT in Modena, Italy from 2003 to June 2015. Methods: frailty index (FI) was constructed from 30 health variables. It was used both as a continuous score and as a categorical variable, defining 'most frail' a FI > 0.45. FI change across transplant (deltaFI, ΔFI) was calculated as the difference between year 1 FI (FI-Y1) and pre-transplant FI (FI-t0). The outcomes measures were mortality and "otpimal LT" (defined as being alive without multi-morbidity). Results: Median value of FI-t0 was 0.48 (IQR 0.42-0.52), FI-Y1 was 0.31 (IQR 0.26-0.41). At year five mortality rate was 45%, "optimal transplant" rate at year 1 was 38%. All the patients who died in the post-LT were most frail in the pre-LT. ΔFI was a predictor of mortality after correction for age and MELD (HR = 1.10, p = 0.006) and was inversely associated with optimal transplant after correction for age (HR = 1.04, p = 0.01). Conclusions: We validated FI as a valuable health measure in HIV transplant. In particular, we found a relevant correlation between FI strata at baseline and mortality and a statistically significant correlation between, ΔFI and survival rate.

2017 - Donor safety in living donor liver donation: An Italian multicenter survey [Articolo su rivista]
Lauterio, A; Di Sandro, S; Gruttadauria, S; Spada, M; Di Benedetto, F; Baccarani, U; Regalia, E; Melada, E; Giacomoni, A; Cescon, M; Cintorino, D; Ercolani, G; Rota, M; Rossi, G; Mazzaferro, V; Risaliti, A; Pinna, Ad; Gridelli, B; De Carlis, L
abstract

2017 - Heavily calcified gastrointestinal stromal tumors: Pathophysiology and implications of a rare clinicopathologic entity [Articolo su rivista]
Salati, M.; Orsi, G.; Bonetti, L. R.; Di Benedetto, F.; Longo, G.; Cascinu, S.
abstract

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract, and are characterized by a broad spectrum of clinical, histological and molecular features at presentation. Although focal and scattered calcifications are not uncommon within the primary tumor mass, heavy calcification within a GIST is rarely described in the literature and the clinical-biological meaning of this feature remains unclear. Cases with such an atypical presentation are challenging and may be associated with diagnostic pitfalls. Herein, we report a gastric GIST with the unusual presentation of prominent calcifications that was identified incidentally on imaging during a post-trauma diagnostic work-up. The patient underwent laparoscopic surgery with a radical resection of the mass, which was subsequently characterized by histological analysis as spindle-shaped tumor cells, positive for CD117/c-KIT, CD34 and DOG1, and with calcified areas. Given the intermediate risk of recurrence, no adjuvant therapy was recommended and the patient underwent regular follow-up for 22 mo, with no evidence of relapse. Our case can be considered of interest because of the rarity of clinical presentation and the uniquely large size of the GIST at diagnosis (longest diameter exceeding 9 cm). In closing, we discuss the pathophysiology and clinical implications of calcifications in GISTs by reviewing the most up-to-date relevant literature.

2017 - In vivo bioluminescence-based monitoring of liver metastases from colorectal cancer: An experimental model [Articolo su rivista]
Magistri, Paolo; Battistelli, Cecilia; Toietta, Gabriele; Strippoli, Raffaele; Sagnotta, Andrea; Forgione, Antonello; Di Benedetto, Fabrizio; Uccini, Stefania; Vittorioso, Paola; D’Angelo, Francesco; Aurello, Paolo; Ramacciato, Giovanni; Nigri, Giuseppe
abstract

In this study we aimed to develop a new in vivo bioluminescence-based tool to monitor and to quantify colon cancer (CC) liver metastasis development. HCT 116 cells were transducted with pLenti6/V5-DEST- fLuc for constitutive expression of firefly luciferase. Infection was monitored analyzing endogenous bioluminescence using the IVIS Lumina II in vivo Imaging System and a positive clone constitutively expressing luciferase (HCT 116-fLuc) was isolated. HCT 116-fLuc cells were left untreated or treated with 1 M GDC-0449, a Hedgehog pharmacological inhibitor. Moreover, 1 × 106 HCT 116-fLuc cells were implanted via intra-splenic injection in nude mice. Bioluminescence was analyzed in these mice every 7 days for 5 weeks. After that, mice were sacrificed and bioluminescence was analyzed on explanted livers. We found that in vitro bioluminescence signal was significantly reduced when HCT 116-fLuc cells were treated with GDC-0449. Regarding in vivo data, bioluminescence sources consistent with hepatic anatomical localization were detected after 21 days from HCT 116-fLuc intrasplenic injection and pro- gressively increased until the sacrifice. The presence of liver metastasis was further confirmed by ex-vivo bioluminescence analysis of explanted livers. Our in vitro results suggest that inhibition of Hedgehog pathway may hamper CC cell proliferation and impel for further studies. Regarding in vivo data, we set- up a strategy for liver metastasis visualization, that may allow follow-up and quantification of the entire metastatic process. This cost-effective technique would reduce experimental variability, as well as the number of sacrificed animals.

2017 - Laparoscopic Liver Resection of Right Posterior Segments for Hepatocellular Carcinoma on Cirrhosis [Articolo su rivista]
Tarantino, Giuseppe; Magistri, Paolo; Serra, Valentina; Berardi, Giammauro; Assirati, Giacomo; Ballarin, Roberto; Di Benedetto, Fabrizio
abstract

Laparoscopic liver resection (LLR) is now widely adopted for the treatment of liver malignancies. Liver resection with laparoscopic approach was first adopted for tumors located in the peripheral portion of the anterolateral segments of the liver, but recent experiences in literature modified the attitude toward that approach. We herein report our technique and outcomes of LLR for hepatocellular carcinoma (HCC) located in the right-posterior segments of the liver (VI and VII).

2017 - Laparoscopic versus robotic surgery for hepatocellular carcinoma: the first 46 consecutive cases [Articolo su rivista]
Magistri, P; Tarantino, G; Guidetti, C; Assirati, G; Olivieri, T; Ballarin, R; Coratti, A; Di Benedetto, F
abstract

Hepatocellular carcinoma has a growing incidence worldwide, and represents a leading cause of death in patients with cirrhosis. Nowadays, minimally invasive approaches are spreading in every field of surgery and in liver surgery as well.

2017 - Liver transplantation and combined hepatocellular-cholangiocarcinoma: Feasibility and outcomes [Articolo su rivista]
Magistri, P.; Tarantino, G.; Serra, V.; Guidetti, C.; Ballarin, R.; Di Benedetto, F.
abstract

Introduction Combined hepatocellular-cholangiocarcinoma (CHC or cHCC-CC) is a rare primary liver tumor displaying histological features of both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Most patients are not suitable for surgery because of the advanced stage of the disease at the moment of diagnosis. We decided to review the literature in order to identify the outcomes after liver transplantation for CHC and to clarify which is the most appropriate treatment. Material and methods A systematic literature search was performed. Studies reporting outcomes of liver transplantation (LT) for CHC and studies comparing oncologic outcomes after LT versus liver resection (LR) for CHC were included in this review. Results The mean 5-y Disease Free Survival (DFS) reported in literature is 45.4%, while the mean 5-y overall survival (OS) is 41.8%, analyzing a cohort of 418 cases. The mean DSF in our series after LT was 7.97 months, while the mean OS was 11.7 months. Conclusions LT should be avoided for the treatment of CHC, in order to allocate organs for more appropriate diseases. Moreover, surgical resections, and in particular major hepatectomies, seem to be associated with acceptable outcomes. An accurate preoperative management is needed, and the use of PET-CT when differential diagnosis is difficult should be considered.

2017 - Long term follow-up and outcome of liver transplantation from hepatitis B surface antigen positive donors [Articolo su rivista]
Ballarin, Roberto; Cucchetti, Alessandro; Russo, Francesco Paolo; Magistri, Paolo; Cescon, Matteo; Cillo, Umberto; Burra, Patrizia; Pinna, Antonio Daniele; Di Benedetto, Fabrizio
abstract

Liver transplant for hepatitis B virus (HBV) currently yields excellent outcomes: it allows to rescue patients with an HBV-related advanced liver disease, resulting in a demographical modification of the waiting list for liver transplant. In an age of patient-tailored treatments, in liver transplantation as well the aim is to offer the best suitable graft to the patient who can benefit from it, also expanding the criteria for organ acceptance and allocation. With the intent of developing strategies to increase the donor pool, we set-up a multicenter study involving 3 Liver Transplant Centers in Italy: patients undergoing liver transplantation between March 03, 2004, and May 21, 2010, were retrospectively evaluated. 1408 patients underwent liver transplantation during the study period, 28 (2%) received the graft from hepatitis B surface antigen positive (HBsAg)-positive deceased donors. The average follow-up after liver transplantation was 63.7 mo [range: 0.1-119.4; SD ± 35.8]. None Primary nonfunction, re-liver transplantation, early or late hepatic artery thrombosis occurred. The 1-, 3- and 5-year graft and patient survival resulted of 85.7%, 82.1%, 78.4%. Our results suggest that the use of HBsAgpositive donors liver grafts is feasible, since HBV can be controlled without affecting graft stability. However, the selection of grafts and the postoperative antiviral therapy should be managed appropriately.

2017 - Microenvironment inflammatory infiltrate drives growth speed and outcome of hepatocellular carcinoma: a prospective clinical study [Articolo su rivista]
Critelli, Rosina; Milosa, Fabiola; Faillaci, Francesca; Condello, Rosario; Turola, Elena; Marzi, Luca; Lei, Barbara; Dituri, Francesco; Andreani, Silvia; Sighinolfi, Pamela; Manni, Paola; Maiorana, Antonino; Caporali, Cristian; di Benedetto, Fabrizio; Del Buono, Mariagrazia; De Maria, Nicola; Schepis, Filippo; Martinez-Chantar, Maria-Luz; Giannelli, Gianluigi; Villa, Erica
abstract

In HCC, tumor microenvironment, heavily influenced by the underlying chronic liver disease, etiology and stage of the tissue damage, affects tumor progression and determines the high heterogeneity of the tumor. Aim of this study was to identify the circulating and tissue components of the microenvironment immune-mediated response affecting the aggressiveness and the ensuing clinical outcome. We analyzed the baseline paired HCC and the surrounding tissue biopsies from a prospective cohort of 132 patients at the first diagnosis of HCC for immunolocalization of PD-1/PD-L1, FoxP3, E-cadherin, CLEC2 and for a panel of 82 microRNA associated with regulation of angiogenesis, cell proliferation, cell signaling, immune control and autophagy. Original microarray data were also explored. Serum samples were analyzed for a panel of 19 cytokines. Data were associated with biochemical data, histopathology and survival. Patients with a more aggressive disease and shorter survival, who we named fast-growing accordingly to the tumor doubling time, at presentation had significantly higher AFP levels, TGF-β1 and Cyphra 21-1 levels. Transcriptomic analysis evidenced a significant downregulation of CLEC2 and upregulation of several metalloproteinases. A marked local upregulation of both PD-1 and PD-L1, a concomitant FoxP3-positive lymphocytic infiltrate, a loss of E-cadherin, gain of epithelial-mesenchymal transition (EMT) phenotype and extreme poor differentiation at histology were also present. Upregulated microRNA in fast-growing HCCs are associated with TGF-β signaling, angiogenesis and inflammation. Our data show that fast HCCs are characterized not only by redundant neo-angiogenesis but also by unique features of distinctively immunosuppressed microenvironment, prominent EMT, and clear-cut activation of TGFβ1 signaling in a general background of long-standing and permanent inflammatory state.

2017 - Multimodal oncological approach in patients affected by recurrent hepatocellular carcinoma after liver transplantation [Articolo su rivista]
Guerrini, Gp; Berretta, M; Tarantino, G; Magistri, P; Pecchi, A; Ballarin, R; Di Benedetto, F
abstract

Hepatocellular Carcinoma (HCC) represents the fifth most common malignancy and the third cancer-related cause of death worldwide. Liver transplantation (LT) is an excellent treatment for patients with small HCC associated with cirrhosis. The purpose of this review is to investigate the possible strategies for the treatment of HCC recurrence after LT based on current clinical evidence.

2017 - Prevention of hepatitis C recurrence by bridging sofosbuvir/ribavirin from pre- to post-liver transplant: A real-life strategy [Articolo su rivista]
Donato, M. F.; Morelli, C.; Romagnoli, R.; Invernizzi, F.; Mazzarelli, C.; Iemmolo, R. M.; Montalbano, M.; Lenci, I.; Bhoori, S.; Pieri, G.; Berardi, S.; Caraceni, P.; Martini, S.; Angeli, P.; Belli, L. S.; Berardi, S.; Bernabucci, V.; Malinverno, F.; Monico, S.; Ottobrelli, A.; Romano, A.; Strona, S.; Tame, M. R.; Visco-Comandini, U.; Cavenago, M.; De Carlis, L.; Di Benedetto, F.; Dondossola, D.; Ettorre, G. M.; Mazzaferro, V.; Montin, U.; Pinna, A. D.; Rossi, G.; Salizzoni, M.; Tisone, G.
abstract

Background & Aims: Hepatitis C virus (HCV) re-infection following liver transplant (LT) is associated with reduced graft and patient survival. Before transplant, Sofosbuvir/ Ribavirin (SOF/R) treatment prevents recurrent HCV in 96% of those patients achieving viral suppression for at least 4 weeks before transplant. We evaluated whether a bridging SOF-regimen from pre- to post-transplant is safe and effective to prevent HCV recurrence in those patients with less than 4 weeks of HCV-RNA undetectability at the time of transplant. Methods: From July 2014 SOF/R was given in 233 waitlisted HCV cirrhotics with/ without hepatocellular carcinoma (HCC) within an Italian Compassionate Program. One hundred patients were transplanted and 31 patients (31%) treated with SOF/R bridging therapy were studied. Results: Liver transplant indication in bridge subgroup was HCC in 22 and decompensated cirrhosis in 9. HCV-genotype was 1/4 in 18 patients. SOF 400 mg/day and R (median dosage 800 mg/day) were given for a median of 35 days before LT. At transplant time, 19 patients were still HCV-RNA positive (median HCV-RNA 58 IU/mL). One recipient had a virological breakthrough at week 4 post-transplant; one died, on treatment, 1-month post-transplant for sepsis and 29/31 achieved a 12-week sustained virological response (94%). Acute cellular rejection occurred in three recipients. On September 2016, 30 recipients (97%) were alive with a median follow-up of 18 months (range 13-25). Conclusions: In patients with suboptimal virological response at LT, a bridging SOF/R regimen helps avoiding post-transplant graft reinfection.

2017 - Promotion of proliferation and metastasis of hepatocellular carcinoma by LncRNA00673 based on the targeted-regulation of notch signaling pathway [Articolo su rivista]
Magistri, P; Battistelli, C; Assirati, G; Mereu, F; Tarantino, G; Guerrini, Gp; Ballarin, R; Di Benedetto, F
abstract

we read with great interest the paper by Dr. Chen et al1, recently published in European Review for Medical and Pharmacological Sciences and titled ‘‘Promotion of proliferation and metastasis of hepatocellular carcinoma by LncRNA00673 based on the targeted-regulation of notch signaling pathway’’. Authors concluded that lncRNA00673 is highly expressed and may be a potential target for the treatment of Hepatocellular Carcinoma (HCC). Moreover, according to authors, it can promote the proliferation and metastasis of HCC by the regulation of Notch signaling pathway. We congratulate the authors for their interesting work.

2017 - Quantitative Assessment of Pancreatic Texture Using a Durometer: A New Tool to Predict the Risk of Developing a Postoperative Fistula [Articolo su rivista]
Marchegiani, G.; Ballarin, R.; Malleo, G.; Andrianello, S.; Allegrini, V.; Pulvirenti, A.; Paini, M.; Secchettin, E.; Boriero, F.; Di Benedetto, F.; Bassi, C.; Salvia, R.
abstract

Background: Pancreatic texture is one of the key predictors of postoperative pancreatic fistula (POPF) after pancreatoduodenectomy (PD). Currently, the “gold standard” for assessment of pancreatic texture is surgeon’s subjective evaluation through manual palpation. Aim: To evaluate a new “durometer” that is able to assess quantitatively the pancreatic stiffness by measuring its elastic module (i.e., the resistance offered by the pancreatic stump when elastically deformed expressed in mPa). Methods: Measurements were obtained from the pancreatic remnant during 138 consecutive PDs performed at the Department of General and Pancreatic Surgery—The Pancreas Institute, University of Verona Hospital Trust. Values were correlated to clinical features and, in particular, with the senior surgeon’s evaluation of pancreatic texture (hard/soft). Sixteen beating-heart donors were used as a control group to assess the stiffness of a non-pathologic pancreas. Univariate analysis was performed for the assessment of POPF predictors. Results: Durometry allowed segregating between non-pathologic, soft and hard pancreas according to surgeon’s evaluation (mean values 111 vs. 196 vs. 366 mPa, p < 0.01). There were no significant differences in stiffness with regard to histology, BMI, and neoadjuvant therapy. Larger tumors (>20 mm) and male sex were associated with greater stiffness on univariate analysis. Pancreatic texture, pancreatic duct size, BMI, prior neoadjuvant therapy, and histology were predictors of POPF. Patients who developed POPF showed a lesser stiffness (178 vs. 261 mPa, p = 0.05). Conclusion: Assessment of pancreatic stiffness using a durometer correlated with the surgeon’s evaluation of pancreatic texture. Measurement of pancreatic parenchymal stiffness is reliable and correlates with the development of POPF.

2017 - Robotic liver donor right hepatectomy: A pure, minimally invasive approach [Articolo su rivista]
Magistri, P.; Tarantino, G.; Ballarin, R.; Coratti, A.; Di Benedetto, F.
abstract

2017 - Robotic liver surgery is the optimal approach as bridge to transplantation [Articolo su rivista]
Magistri, Paolo; Tarantino, Giuseppe; Ballarin, Roberto; Coratti, Andrea; Di Benedetto, Fabrizio
abstract

The role of minimally invasive liver surgery as a bridge to transplantation is very promising but still underestimated. However, it should be noted that surgical approach for hepatocellular carcinomas (HCC) is not merely a technical or technological issue. Nowadays, the epidemiology of HCC is evolving due to the increasing role of non-alcoholic fatty-liver-disease, and the emerging concerns on direct-acting antivirals against hepatitis C virus in terms of HCC incidence. Therefore, a fully multidisciplinary study of the cirrhotic patient is currently more important than ever before, and the management of those patients should be reserved to tertiary referral hepatobiliary centers. In particular, minimally invasive approach to the liver showed several advantages compared to the classical open procedure, in terms of: (1) the small impact on abdominal wall; (2) the gentle manipulation on the liver; (3) the limited surgical trauma; and (4) the respect of venous shunts. Therefore, more direct indications should be outlined also in the Barcelona Clinic Liver Cancer model. We believe that treatment of HCC in cirrhotic patients should be reserved to tertiary referral hepatobiliary centers, that should offer patient-tailored approaches to the liver disease, in order to provide the best care for each case, according to the individual comorbidities, risk factors, and personal quality of life expectations.

2017 - Robotic versus laparoscopic distal pancreatectomy: An up-to-date meta-analysis [Articolo su rivista]
Guerrini, G. P.; Lauretta, A.; Belluco, C.; Olivieri, M.; Forlin, M.; Basso, S.; Breda, B.; Bertola, G.; Di Benedetto, F.
abstract

Background: Laparoscopic distal pancreatectomy (LDP) reduces postoperative morbidity, hospital stay and recovery as compared with open distal pancreatectomy. Many authors believe that robotic surgery can overcome the difficulties and technical limits of LDP thanks to improved surgical manipulation and better visualization. Few studies in the literature have compared the two methods in terms of surgical and oncological outcome. The aim of this study was to compare the results of robotic (RDP) and laparoscopic distal pancreatectomy. Methods: A systematic review and meta-analysis was conducted of control studies published up to December 2016 comparing LDP and RDP. Two Reviewers independently assessed the eligibility and quality of the studies. The meta-analysis was conducted using either the fixed-effect or the random-effect model. Results: Ten studies describing 813 patients met the inclusion criteria. This meta-analysis shows that the RDP group had a significantly higher rate of spleen preservation [OR 2.89 (95% confidence interval 1.78-4.71, p < 0.0001], a lower rate of conversion to open OR 0.33 (95% CI 0.12-0.92), p = 0.003] and a shorter hospital stay [MD -0.74; (95% CI -1.34 -0.15), p = 0.01] but a higher cost than the LDP group, while other surgical outcomes did not differ between the two groups. Conclusion: This meta-analysis suggests that the RDP procedure is safe and comparable in terms of surgical results to LDP. However, even if the RDP has a higher cost compared to LDP, it increases the rate of spleen preservation, reduces the risk of conversion to open surgery and is associated to shorter length of hospital stay.

2017 - Surgery in biliary lithiasis: from the traditional “open” approach to laparoscopy and the “rendezvous” technique [Articolo su rivista]
Tarantino, G; Magistri, P; Ballarin, R; Assirati, G; Di Cataldo, Antonio; Di Benedetto, F
abstract

According to the current literature, biliary lithiasis is a worldwide-diffused condition that affects almost 20% of the general population. The rate of common bile duct stones (CBDS) in patients with symptomatic cholelithiasis is estimated to be 10% to 33%, depending on patient's age. Compared to stones in the gallbladder, the natural history of secondary CBDS is still not completely understood. It is not clear whether an asymptomatic choledocholithiasis requires treatment or not. For many years, open cholecystectomy with choledochotomy and/or surgical sphincterotomy and cleaning of the bile duct were the gold standard to treat both pathologies. Development of both endoscopic retrograde cholangiopancreatography (ERCP) and laparoscopic surgery, together with improvements in diagnostic procedures, influenced new approaches to the management of CBDS in association with gallstones.

2017 - The Evolving Role of Local Treatments for HCC in the Third Millennium [Articolo su rivista]
Magistri, Paolo; Tarantino, Giuseppe; Ballarin, Roberto; Berretta, Massimiliano; Pecchi, Annarita; Ramacciato, Giovanni; DI Benedetto, Fabrizio
abstract

Hepatocellular carcinoma (HCC) represents the fifth most common malignancy and the third cancer-related cause of death worldwide. The aim of this review was to clarify the role of local treatments for HCC, analyzing the indications and defining future perspectives.

2017 - Validation of the AFP model as a predictor of HCC recurrence in patients with viral hepatitis-related cirrhosis who had received a liver transplant for HCC [Articolo su rivista]
Notarpaolo, Andrea; Layèse, Richard; Magistri, Paolo; Gambato, Maria; Colledan, Michele; Magini, Giulia; Miglioresi, Lucia; Vitale, Alessandro; Vennarecci, Giovanni; Ambrosio Cecilia, D; Burra, Patrizia; DI BENEDETTO, Fabrizio; Fagiuoli, Stefano; Colasanti, Marco; Maria Ettorre, Giuseppe; Andreoli, Arnoldo; Cillo, Umberto; Laurent, Alexis; Katsahian, Sandrine; Audureau, Etienne; Roudot-Thoraval, Françoise; Duvoux, Christophe
abstract

2016 - Angiogenesis inhibitors for the treatment of hepatocellular carcinoma [Articolo su rivista]
Berretta, M.; Rinaldi, L.; Di Benedetto, F.; Lleshi, A.; Re, V. D.; Facchini, G.; De Paoli, P.; Di Francia, R.
abstract

Background: Angiogenesis inhibitors have become an important therapeutic approach in the treatment of hepatocellular carcinoma (HCC) patients. The therapeutic inhibition of angiogenesis of Sorafenib in increasing overall survival of patients with HCC is a fundamental element of the treatment of this disease. Considering the heterogeneous aspects of HCC and to boost therapeutic efficacy, prevail over drug resistance and lessen toxicity, adding antiangiogenic drugs to antiblastic chemotherapy (AC), radiation therapy or other targeted drugs have been evaluated. The matter is additionally complicated by the combination of antiangiogenesis with further AC or biologic drugs. To date, no planned approach to understand which patients are more responsive to a given type of antiangiogenic treatment is available. Conclusion: Large investments in the clinical research are essential to improve treatment response and minimize toxicities for patients with HCC. Future investigations will need to focus on utilizing patterns of genetic information to classify HCC into groups that display similar prognosis and treatment sensitivity, and combining targeted therapies with AC producing enhanced anti-tumor effect. In this review the current panel of available antiangiogenic therapies for the treatment of HCC have been analyzed. In addition current clinical trials are also reported herein.

2016 - Early introduction of subcutaneous hepatitis B immunoglobulin following liver transplantation for hepatitis B virus infection: A prospective, multicenter study [Articolo su rivista]
De Simone, P.; Romagnoli, R.; Tandoi, F.; Carrai, P.; Ercolani, G.; Peri, E.; Zamboni, F.; Mameli, L.; Di Benedetto, F.; Cillo, U.; De Carlis, L.; Lauterio, A.; Lupo, L.; Tisone, G.; Prieto, M.; Loinaz, C.; Mas, A.; Suddle, A.; Mutimer, D.; Roche, B.; Wartenberg-Demand, A.; Niemann, G.; Bohm, H.; Samuel, D.
abstract

Background. Subcutaneous administration of hepatitis B immunoglobulin (HBIg) is effective in preventing hepatitis B virus (HBV) recurrence after liver transplantation, but early conversion to subcutaneous administration is undocumented. Methods. In a prospective study, patients transplanted for terminal liver disease due to HBV infection who were HBV DNA-negative at transplant were switched by week 3 posttransplantation from intravenous to subcutaneous HBIg (500 or 1000 IU weekly or fortnightly, adjusted according to serumanti-HBs trough level) if they were HBsAg- and HBV-DNA negative at time of switch. All patients concomitantly received nucleos(t)ide analogue antiviral therapy. Primary endpoint was failure rate by month 6, defined as serum anti- HBs of 100 IU/L or less or HBV reinfection despite serum anti-HBs greater than 100 IU/L. Results. Of 49 patients treated, 47 (95.9%) continued treatment until month 6. All patients achieved administration by a caregiver or self-injection by week 14. No treatment failures occurred. Mean anti-HBs declined progressively to month 6, plateauing at a protective titer of approximately 290 IU/L. All patients tested for HBV DNA remained negative (45/45). Only 1 adverse event (mild injection site hematoma) was assessed as treatment-related. Conclusions. Introduction of subcutaneous HBIg administration by week 3 posttransplantation, combined with HBV virostatic prophylaxis, is effective and convenient for preventing HBV recurrence.

2016 - Incidental Intra-Hepatic Cholangiocarcinoma and Hepatocholangiocarcinoma in Liver Transplantation: A Single-Center Experience [Articolo su rivista]
Serra, V.; Tarantino, G.; Guidetti, C.; Aldrovandi, S.; Cuoghi, M.; Olivieri, T.; Assirati, G.; De Ruvo, N.; Magistri, P.; Ballarin, R.; Di Benedetto, F
abstract

Background Cholangiocarcinoma (CCA) is an aggressive malignancy of the biliary tract that is a challenging issue for the medical community, with increasing incidence. Risk factors for CCA are similar to those known for hepatocellular carcinoma (HCC), such as cirrhosis, chronic hepatitis B and C, obesity, diabetes, and alcohol. We describe the outcome and the management of patients who underwent liver transplantation (LT) with an incidental diagnosis of intrahepatic (iCCA) or hepatocholangiocarcinoma (CHC). Methods From 2000 to May 2015, 655 LT were performed LT at the Liver Transplant Center in Modena, Italy. We retrospectively reviewed the pathological data of the explanted livers, finding 5 cases of iCCA or CHC. The pathological examination of the explanted livers showed 1 case of iCCA; 1 case of multifocal HCC associated with a nodule of iCCA; 2 cases of CHC associated with nodules of HCC; and 1 case of CHC associated with iCCA. Mean disease-free survival (DFS) was 15.49 months (1.55-42.04) and mean overall survival (OS) was 24.76 months (3.91-75.49). All patients died of recurrent tumor progression. Results iCCA incidental finding after LT affects patient outcomes, massively causing OS and DFS reduction. We stress the necessity of a more accurate selection of the candidates whenever an augmented risk of iCCA or CHC is present. Conclusions Further investigations are required to better understand the role of LT in these patients and to define the best management for them once they have been transplanted and the histological examination reveals the presence of iCCA or CHC.

2016 - Kidney Transplantation in HIV-Infected Recipients: Therapeutic Strategy and Outcomes in Monocentric Experience [Articolo su rivista]
Baisi, Alberto; Nava, F.; Baisi, B.; Rubbiani, E.; Guaraldi, Giovanni; DI BENEDETTO, Fabrizio; Giovannoni, M.; Solazzo, A.; Bonucchi, D.; Cappelli, Gianni
abstract

Background In Human immunodeficiency virus (HIV)-positive patients undergoing kidney transplantation, outcomes and immunosuppression (IS) protocol are not yet established due to infectious and neoplastic risks as well as to pharmacokinetic interactions with antiretroviral therapy (TARV). Methods We report a retrospective, 1-center study on 18 HIV+ patients undergoing, between October 2007 and September 2015, kidney transplantation (13 cases) or combined kidney-liver transplant (5 cases). Inclusion criteria for transplant were based on the Italian National Transplant Center protocol. IS regimen was based on quick tapering of steroids and the use of mTOR inhibitors (mTORi) with low dose of calcineurin inhibitors (CNI). In the early post-transplant period, TARV was based on enfuvirtide, raltegravir, plus 1 or more nucleoside analogues. Results In a mean follow-up of 3.1 years, patient survival rate at 1 and 3 years was, respectively, 86.6% and 84.6%, whereas graft survival was 81.2% and 78.6%. Cumulative rejection rate was 20.0% and 26.6% (1- and 3-year results). Median eGFR (MDRD) was 58.8 mL/min and 51.9 mL/min at 1 and 3 years. We had 9 cases of clinically relevant infections (2 Pneumocystis jirovecii pneumonia, 1 pulmonary aspergillosis, 2 severe sepsis, and 4 HCV reactivation) as well as 1 case (5.5%) of HIV reactivation. Conclusions IS therapy based on mTORi and low CNI dose ensures good graft survival, low rate of acute rejection, limited drug toxicity, and control of HIV disease. TARV has no significant interaction with IS therapy.

2016 - Liver Retransplantation in Patients with HIV-1 Infection: An International Multicenter Cohort Study [Articolo su rivista]
Aga¼ero, F.; Rimola, A.; Stock, P.; Grossi, P.; Rockstroh, J. K.; Agarwal, K.; Garzoni, C.; Barcan, L. A.; Maltez, F.; Manzardo, C.; Mari, M.; Ragni, M. V.; Anadol, E.; Di Benedetto, F.; Nishida, S.; Gastaca, M.; Mira, J. M.; Pedreira, J. D.; Castro, M. A.; Lapez, S.; Sua¡rez, F.; Vazquez, P.; Blanch, J.; Brunet, M.; Cervera, C.; de Lazzari, E.; Fondevila, C.; Forner, A.; Fuster, J.; Freixa, N.; GarcA­a-Valdecasas, J. C.; Gil, A.; Gatell, J. M.; Laguno, M.; Marta­nez, M.; Mallolas, J.; Monras, M.; Moreno, A.; Murillas, J.; Paredes, D.; Pacopyrightrez, I.; Torres, F.; Tural, C.; Tuset, M.; Antela, A.; Fernandez, J.; Losada, E.; Varo, E.; Lozano, R.; Araiz, J. J.; Barrao, E.; Letona, S.; Luque, P.; Navarro, A.; Sanjoaqua­n, I.; Serrano, T.; Tejero, E.; Salcedo, M.; BaA+/-ares, R.; Calleja, J.; Berenguer, J.; Cosa­n, J.; Gutiacopyrightrrez, I.; Lapez, J. C.; Miralles, P.; Rama­rez, M.; Rincan, D.; Sanchez, M.; Jimacopyrightnez, M.; de la Cruz, J.; Ferna¡ndez, J. L.; Lozano, J. M.; Santoyo, J.; Rodrigo, J. M.; Sua¡rez, M. A.; Rodra­guez, M.; Alonso, M. P.; Asensi, V.; Gonza¡lez, M. L.; GonzA¡lez-Pinto, I.; Rafecas, A.; Carratala¡, J.; Fabregat, J.; Ferna¡ndez, N.; Xiol, X.; Montejo, M.; Bustamante, J.; Ferna¡ndez, J. R.; Montejo, E.; Ortiz de Urbina, J.; Ruiz, P.; Sua¡rez, M. J.; Testillano, M.; Valdivieso, A.; Ventoso, A.; Abradelo, M.; Costa, J. R.; Fundora, Y.; Jimacopyrightnez, S.; Meneu, J. C.; Moreno, E.; Moreno, V.; Olivares, S. P.; Pacopyrightrez, B.; Pulido, F.; Rubio, R.; Blanes, M.; Aguilera, V.; Berenguer, M.; Lapez, J.; Lapez, R.; Prieto, M.; FariA+/-as, M. C.; Arnaiz, A.; Casafont, F.; Echevarria, S.; Fa¡brega, E.; Garca­a, J. D.; Gamez, M.; Gutiacopyrightrrez, J. M.; Peralta, F. G.; Teira, R.; Moreno, S.; Barcena, R.; Del Campo, S.; Fortaºn, J.; Moreno, A. M.; Torre-Cisneros, J.; Barrera, P.; Camacho, A.; Cantisa¡n, S.; Castan, J. J.; de la Mata, M.; Lara, M. R.; Natera, C.; Rivero, A.; Vidal, E.; Castells, L. I.; Charco, R.; Esteban, J. I.; Gavalda¡, J.; Len, O.; Pahissa, A.; Ribera, E.; Vargas, V.; Pons, J. A.; Cordero, E.; Bernal, C.; Cisneros, J. M.; Gamez, M. A.; Pascasio, J. M.; Rodra­guez, M. J.; Sayazo, M.; Sousa, J. M.; Sua¡rez, G.; Gonza¡lez, J.; Aznar, E.; Barquilla, E.; Esteban, H.; Krahe, L.; Moyano, B.; de la Rosa, G.; Mahillo, B.; Roland, M.; Ascher, N.; Roberts, J.; Freise, C.; Terrault, N.; Carlson, L.; Beatty, G.; Chin-Hong, P.; Dove, L.; Emond, J.; Lobritto, S.; Neu, N.; Yin, M.; Kumar, A.; Ringe, B.; Jacobson, J.; Sass, D.; Diego, J.; Tzakis, A.; Roth, D.; Schiff, E.; Burke, G.; Jayaweera, D.; Olthoff, K.; Blumberg, E.; Bloom, R.; Reddy, R.; Ragni, M.; Shapiro, R.; De Vera, M. E.; Shakil, O.; Simon, D.; Cohen, S. M.; Dodson, S. F.; Jensik, S.; Saltzberg, S.; Stosor, T.; Green, R.; Baker, T.; Gallon, L.; Scarsi, K.; Hanto, D.; Wong, M.; Curry, M.; Johnson, S.; Pavlakis, M.; Barin, B.; Risaliti, A.; Ancarani, F.; Pinna, A. D.; Morelli, C.; Guaraldi, G.; Tarantino, G.; Baccarani, U.; Tavio, M.; Nanni Costa, A.; Beckebaum, S.; Radecke, K.; Bickel, M.; Sterneck, M.; Zoufaly, A.; Ganten, T.; Stoll, M.; Salzberger, B.; Berg, C.; Kittner, J.; O'Grady, J.; Joshi, D.; Heaton, N.; Smud, A.; Genoud, N.; Cahn, F.; Valledor, A.; Gadano, A.; Barcan, L.; Cusini, A.; Rauch, A.; Furrer, H.; Ma¼ller, N. J.; Khanna, N.; van Delden, C.; Oriol, M.; Manata, M. J.; Correia, F.; Machado, J.; Morbey, A.; Glaria, H.; Veloso, J.; Perdigoto, R.; Pereira, P.; Martins, A.; Barroso, E.
abstract

Liver retransplantation is performed in HIV-infected patients, although its outcome is not well known. In an international cohort study (eight countries), 37 (6%; 32 coinfected with hepatitis C virus [HCV] and five with hepatitis B virus [HBV]) of 600 HIV-infected patients who had undergone liver transplant were retransplanted. The main indications for retransplantation were vascular complications (35%), primary graft nonfunction (22%), rejection (19%), and HCV recurrence (13%). Overall, 19 patients (51%) died after retransplantation. Survival at 1, 3, and 5 years was 56%, 51%, and 51%, respectively. Among patients with HCV coinfection, HCV RNA replication status at retransplantation was the only significant prognostic factor. Patients with undetectable versus detectable HCV RNA had a survival probability of 80% versus 39% at 1 year and 80% versus 30% at 3 and 5 years (p = 0.025). Recurrence of hepatitis C was the main cause of death in the latter. Patients with HBV coinfection had survival of 80% at 1, 3, and 5 years after retransplantation. HIV infection was adequately controlled with antiretroviral therapy. In conclusion, liver retransplantation is an acceptable option for HIV-infected patients with HBV or HCV coinfection but undetectable HCV RNA. Retransplantation in patients with HCV replication should be reassessed prospectively in the era of new direct antiviral agents.

2016 - Liver Transplantation for Hepatic Trauma: A Study from the European Liver Transplant Registry [Articolo su rivista]
Krawczyk, M.; Grat, M.; Adam, R.; Polak, W. G.; Klempnauer, J.; Pinna, A.; Di Benedetto, F.; Filipponi, F.; Senninger, N.; Foss, A.; Rufian-Pena, S.; Bennet, W.; Pratschke, J.; Paul, A.; Settmacher, U.; Rossi, G.; Salizzoni, M.; Fernandez-Selles, C.; De Rituerto, S. T. M.; Gomez-Bravo, M. A.; Pirenne, J.; Detry, O.; Majno, P. E.; Nemec, P.; Bechstein, W. O.; Bartels, M.; Nadalin, S.; Pruvot, F. R.; Mirza, D. F.; Lupo, L.; Colledan, M.; Tisone, G.; Ringers, J.; Daniel, J.; Torra, R. C.; Gonzalez, E. M.; Canizares, R. B.; Martinez, V. C. -M.; Rodriguez, F. S. J.; Yilmaz, S.; Remiszewski, P.
abstract

Background. Liver transplantation is the most extreme form of surgical management of patients with hepatic trauma, with very limited literature data supporting its use. The aim of this study was to assess the results of liver transplantation for hepatic trauma. Methods. This retrospective analysis based on European Liver Transplant Registry comprised data of 73 recipients of liver transplantation for hepatic trauma performed in 37 centers in the period between 1987 and 2013. Mortality and graft loss rates at 90 days were set as primary and secondary outcome measures, respectively. Results. Mortality and graft loss rates at 90 days were 42.5% and 46.6%, respectively. Regarding general variables, cross-clamping without extracorporeal veno-venous bypass was the only independent risk factor for both mortality (P = 0.031) and graft loss (P = 0.034). Regarding more detailed factors, grade of liver trauma exceeding IV increased the risk of mortality (P = 0.005) and graft loss (P = 0.018). Moreover, a tendency above the level of significance was observed for the negative impact of injury severity score (ISS) on mortality (P = 0.071). The optimal cutoff for ISS was 33, with sensitivity of 60.0%, specificity of 80.0%, positive predictive value of 75.0%, and negative predictive value of 66.7%. Conclusions. Liver transplantation seems to be justified in selected patients with otherwise fatal severe liver injuries, particularly in whom cross-clamping without extracorporeal bypass can be omitted. The ISS cutoff less than 33 may be useful in the selection process.

2016 - Metastases from renal cell cancer to the thyroid gland. a systematic review of 175 cases between 1964 and 2016 [Articolo su rivista]
D'Angelo, Francesco; Magistri, Paolo; Antolino, Laura; Socciarelli, Fabio; Olivieri, Tiziana; Canegallo, Fiorella; Bollanti, Lucilla; Aurello, Paolo; Di Benedetto, Fabrizio; Ramacciato, Giovanni
abstract

Abstract – Background: Renal Cell Cancer (RCC) is the most common extra-thyroid cancer metastasizing to the thyroid gland and has been responsible for 48.1% metastases of Non-Thyroid Malignancies (NTMs) to the thyroid in the past decade. Metastases to the thyroid gland have been reported in 1.4%-3% of patients undergoing thyroid surgery for thyroid malignancies. We systematically reviewed the literature from 1964 to 2016 and herein present our experience. Patients and Methods: The research was systematically performed on Pubmed, EMbase and Cochrane Library databases by entering the strings: “renal carcinoma AND thyroid metastasis” or “renal carcinoma AND thyroid metastases” or “hypernephroma AND thyroid metastasis (or metastases)”. Results: 175 cases were retrieved and 90 were included in the study since they fulfilled the inclusion criteria by reporting gender, age, latency of metastases presentation after nephrectomy, jugular vein infiltration and other sites of metastasis (when applicable). The mean age of thyroid metastases presentation is 64.4 years and the mean latency after a nephrectomy is 9.1 years (range 0-24). Fine needle aspiration biopsy (FNAB) failed to provide the correct diagnosis in 28.7% of patients with thyroid metastases from RCC. Conclusions: Given the long latency, RCC follow-up program should be longer than recommended at present and implemented with an ultrasound scan of the neck.

2016 - Multimodal approach of advanced gastric cancer: based therapeutic algorithm [Articolo su rivista]
Berretta, S; Berretta, M; Fiorica, F; Di Francia, R; Magistri, P; Bertola, G; Fisichella, R; Canzonieri, V; Tarantino, G; Di Benedetto, F
abstract

Gastric cancer (GC) is the third leading cause of cancer death in both sexes worldwide, with the highest estimated mortality rates in Eastern Asia and the lowest in Northern America. However, the availability of modern treatment has improved the survival and the prognosis is often poor due to biological characteristics of the disease. In oncology, we are living in the "Era" of target treatment and, to know biological aspects, prognostic factors and predictive response informations to therapy in GC is mandatory to apply the best strategy of treatment.The purpose of this review, according to the recently published English literature, is to summarize existing data on prognostic aspects and predictive factors to response to therapy in GC and to analyze also others therapeutic approaches (surgery and radiotherapy) in locally, locally advanced and advanced GC. Moreover, the multidisciplinary approach (chemotherapy, surgery and radiotherapy) can improve the prognosis of GC. The purpose of this review, according to the recently published English literature, is to summarize existing data on prognostic aspects and predictive factors to response to therapy in GC and to analyze also others therapeutic approaches (surgery and radiotherapy) in locally, locally advanced and advanced GC. Moreover, the multidisciplinary approach (chemotherapy, surgery and radiotherapy) can improve the prognosis of GC.

2016 - New entities in the treatment of hepatocellular carcinoma: HIV-positive and elderly patients [Capitolo/Saggio]
Berretta, M.; De Re, V.; De Paoli, P.; Canzonieri, V.; Di Francia, R.; Di Benedetto, F.; Tirelli, U.
abstract

The hepatocellular carcinoma (HCC) is the most common primary cancer of the liver and, according to the WHO report, the fourth commonest cause of death. The estimated incidence of new cases worldwide is about 500,000-1,000,000 per year, causing 600,000 deaths globally per year. The incidence of HCC has been rising in developed western countries in the last two decades, along with the emergence of hepatitis C virus infection and to the rise of immigration rates from HBV-endemic countries. In addition, even though the incidence of HCC reaches its highest peak among persons over 65 years, an increased incidence among younger individuals has been noted in the last two decades both in USA and Europe. In the last decades two kinds of HCC patients are more interesting, for clinical characteristics, than typical patients with HCC: elderly and HIV-positive patients. In fact due to the increase of the life expectancy in many countries, HCC represents a new challenge in this particular setting of patients.

2016 - Oncological impact of M-tor inhibitor immunosuppressive therapy after liver transplantation for hepatocellular carcinoma: Review of the literature [Articolo su rivista]
Tarantino, G.; Magistri, P.; Ballarin, R.; Di Francia, R.; Berretta, M.; Di Benedetto, F.
abstract

Background: Hepatocellular Carcinoma (HCC) represents the fifth most common malignancy and the third cancer-related cause of death worldwide. Hepatitis B (HBV) and C (HCV) viral infections and alcohol abuse are the principal etiological factors for HCC. Liver transplantation (LT) is oncologically the preferable approach to HCC, as it can remove all the intrahepatic tumor foci, and also the oncogenic cirrhotic liver. The use of mTOR inhibitors (mTORi) for immunosuppression after LT for HCC has been proposed due to rapamycin antitumor activity. We decided to review the literature to clarify the oncological role of mTORi after liver transplantation for HCC, analyzing both present condition and future perspectives. Material and Methods: A systematic literature search was performed using PubMed, EMBASE, Scopus, and the Cochrane Library Central. The search was limited to studies in humans and to those reported in the English language in the period of time between January 2005 and December 2015. Results: The literature search yielded 93 articles; after duplicates were removed, 77 titles and abstracts were reviewed. Most relevant data and papers are herein reported and discussed. Conclusions: So far, the use of mTORi is encouraging in terms of oncological outcomes for patients underwent LT for HCC, both for prevention and treatment of HCC recurrence although definitive data are still awaited.

2016 - Pancreaticojejunostomy Versus Pancreaticogastrostomy After Pancreaticoduodenectomy: An Up-to-date Meta-Analysis [Articolo su rivista]
Guerrini, G. P.; Soliani, P.; D紓Amico, G.; Di Benedetto, F.; Negri, M.; Piccoli, M.; Ruffo, G.; Orti-Rodriguez, R. J.; Pissanou, T.; Fusai, G.
abstract

Background: The reconstruction of the pancreas after pancreaticoduodenectomy (PD) is a crucial factor in preventing postoperative complications as pancreatic anastomosis failure is associated with a high morbidity rate and contributes to prolonged hospitalization and mortality. Several techniques have been described for the reconstruction of pancreatic digestive continuity in the attempt to minimize the risk of a pancreatic fistula. The aim of this study was to compare the results of pancreaticogastrostomy and pancreaticojejunostomy after PD. Methods: A systematic review and meta-analysis were conducted of randomized controlled trials (RCTs) published up to January 2015 comparing patients with pancreaticogastrostomy (PG group) versus pancreaticojejunostomy (PJ group). Two reviewers independently assessed the eligibility and quality of the studies. The meta-analysis was conducted using either the fixed-effect or the random-effect model. Results: Eight RCTs describing 1,211 patients were identified for inclusion in the study. The meta-analysis shows that the PG group had a significantly lower incidence rate of postoperative pancreatic fistulas [OR 0.64 (95% confidence interval 0.46–0.86), p =.003], intra-abdominal abscesses [OR 0.53 (95% CI, 0.33–0.85), p =.009] and length of hospital stay [MD −1.62; (95% CI 2.63–0.61), p =.002] than the PJ group, while biliary fistula, mortality, morbidity, rate of delayed gastric emptying, reoperation, and bleeding did not differ between the two groups. Conclusion: This meta-analysis suggests that the most effective treatment for reconstruction of pancreatic continuity after pancreatoduodenectomy is pancreaticogastrostomy. However, the advantage of the latter could potentially be demonstrated through further RCTs, including only patients at high risk of developing pancreatic fistulas.

2016 - Predictive value of nodule size and differentiation in HCC recurrence after liver transplantation [Articolo su rivista]
Guerrini, G. P.; Pinelli, D.; Di Benedetto, F.; Marini, E.; Corno, V.; Guizzetti, M.; Aluffi, A.; Zambelli, M.; Fagiuoli, S.; Luca, M. G.; Lucianetti, A.; Colledan, M.
abstract

Background Liver transplantation (LT) is considered the best treatment option for HCC patients with cirrhosis. However, the scarce availability of liver donors and the risk of dropout from the waiting list due to the tumor progression severely limit LT for HCC. In this study, we evaluate the survival and recurrence in a cohort of patients undergoing LT for HCC fulfilling “Milan Criteria” (MC) pre-LT. In this study, we propose the development of a new prognostic score which could improve the accuracy in predicting recurrence post-LT. Methods Between 1997 and 2011, out of 1010 LT performed in our unit, 131 patients had T2 staged HCC (inside MC). The prognostic model predicting HCC recurrence post-LT was derived from Cox regression analysis. The performance of this model was validated in an external cohort of 198 HCC patients transplanted at another center. Results Overall survival at 1–3–5 years was 87%, 74.4%, 68.2%, whereas recurrence-free survival was 94.1%, 81.4%, 77.6%, respectively. Predictive factors for recurrence-free survival included high tumor grading (HR 5.01; p = 0.006) and tumor diameter (HR 1.46; p = 0.045). According to this model, the estimated relative risk of HCC recurrence after LT is given by this formula: 0.382 × (Tumor size [cm]) + 1.613 × (if Grading 3–4). The ROC curve was 0.878 (p < 0.001) in predicting HCC recurrence. Conclusion In conclusion, our study showed that the use of this new prognostic score, taking into account maximal tumor diameter and tumor differentiation, improves the accuracy of Milan criteria in predicting HCC recurrence.

2016 - Redefine staging of hepatocellular carcinoma on a "bench-to-bedside" approach [Articolo su rivista]
Magistri, P; Tarantino, G; Pecchi, A; Ballarin, R; Di Benedetto, F
abstract

2016 - Small-bowel and multivisceral procurement [Capitolo/Saggio]
Di Benedetto, F.; Tarantino, G.
abstract

2016 - The risk of hepatocellular carcinoma after directly acting antivirals for hepatitis C virus treatment in liver transplanted patients: Is it real? [Articolo su rivista]
Strazzulla, A.; Iemmolo, R. M. R.; Carbone, E.; Postorino, M. C.; Mazzitelli, M.; De Santis, M.; Di Benedetto, F.; Cristiani, C. M.; Costa, C.; Pisani, V.; Torti, C.
abstract

Introduction: Since directly acting antivirals (DAAs) for treatment of hepatitis C virus (HCV) were introduced, conflicting data emerged about the risk of hepatocellular carcinoma (HCC) after interferon (IFN)-free treatments. We present a case of recurrent, extra-hepatic HCC in a liver-transplanted patient soon after successful treatment with DAAs, along with a short review of literature. Case Presentation: In 2010, a 53-year old man, affected by chronic HCV (genotype 1) infection and decompensated cirrhosis, underwent liver resection for HCC and subsequently received orthotopic liver transplantation. Then, HCV relapsed and, in 2013, he was treated with pegylated-IFN plus ribavirin; but response was null. In 2014, he was treated with daclatasvir plus simeprevir to reach sustained virological response. At baseline and at the end of HCV treatment, computed tomography (CT) scan of abdomen excluded any lesions suspected for HCC. However, alpha-fetoprotein was 2.9 ng/mL before DAAs, increasingupto 183.1 ng/mL at week-24 of follow-up after the completion of therapy. Therefore, CT scan of abdomen was performed again, showing two splenicHCClesions. Conclusions: Overall, nine studies have been published about the risk of HCC after DAAs. Patients with previous HCC should be carefully investigated to confirm complete HCC remission before starting, and proactive follow-up should be performed after DAA treatment.

2016 - The transition from virtual reality to real virtuality: advanced imaging and simulation in general surgery [Articolo su rivista]
Magistri, Paolo; Sampogna, Gianluca; D'Angelo, Francesco; Nigri, Giuseppe; Ramacciato, Giovanni; Di Benedetto, Fabrizio; Forgione, Antonello
abstract

Individual anatomical variations, involvement of organs in neoplastic lesions and consequent preoperative planning are some issues that surgeons have to face every day in their clinical activity. The use of dedicated softwares, together with tools for patient-tailored training, is likely to improve clinical outcomes and patients’ safety. We decided to review the literature to report the current role of virtual reality and simulation in general surgery. A search was systematically performed on Pubmed, EMbase, Cochrane Library and Up ToDate databases. The search was limited to articles written in English from January 2005 through June 2016. Altogether, 1,038 articles were found using this search strategy. All studies, case series and reports in the medical field pertaining to preoperative planning, VR and Augmented Reality (AR) application in general surgery that provided translational data were considered eligible to be included. Two authors independently screened the articles by title, abstract and keywords, and then selected 7 papers to be included in this review (4 for VR, 2 for AR and 1 for preoperative planning). Virtual reality training appears to decrease the operating time and improve the operative performance of surgical trainees with limited laparoscopic experience when compared with no training or with box-trainer training. The ability of virtual reality tools to guide surgeons during complex procedures represents a revolution for increased safety and overcoming minimally invasive surgery-related limitations.

2016 - Thrombelastography-guided blood product use before invasive procedures in cirrhosis with severe coagulopathy: A randomized, controlled trial [Articolo su rivista]
De Pietri, Lesley; Bianchini, Marcello; Montalti, Roberto; De Maria, Nicola; DI MAIRA, Tommaso; Begliomini, Bruno; Gerunda, Giorgio Enrico; DI BENEDETTO, Fabrizio; GARCIA TSAO, Guadalupe; Villa, Erica
abstract

Bleeding is a feared complication of invasive procedures in patients with cirrhosis and significant coagulopathy (as defined by routine coagulation tests), and is used to justify pre-procedure use of fresh frozen plasma (FFP) and/or platelets (PLT). Thromboelastography (TEG) provides a more comprehensive global coagulation assessment than routine tests (INR and platelet count) and its use may avoid unnecessary blood product transfusion in patients with cirrhosis and significant coagulopathy (defined in this study as INR>1.8 and/or platelet count <50x10(3) /µl) who will be undergoing an invasive procedure. Sixty patients were randomly allocated to TEG-guided transfusion strategy or standard of care (SOC)(1:1 TEG:SOC). TEG group would receive FFP if the reaction time (r) >40mm and/or PLT if maximum amplitude (MA) <30mm. All SOC patients received FFP and/or PLT per hospital guidelines. Endpoints were blood product use and bleeding complications. Baseline characteristics of the two groups were similar. Per protocol, all subjects in the SOC group received blood product transfusions vs. 5 in the TEG group (100% vs. 16.7%, p<0.0001). Sixteen SOC (53.3%) received FFP, 10 (33.3%) PLT, and 4 (13.3%) both FFP and PLT. In the TEG group, none received FFP alone (p<0.0001 vs. SOC), 2 received PLT (6.7%)(p=0.009 vs. SOC), and 3 both FFP and PLT (NS). Post-procedure bleeding occurred in only 1 patient (SOC group) after large-volume paracentesis.

2016 - Totally robotic isolated caudate-lobe liver resection for hydatid disease: report of a case [Articolo su rivista]
Di Benedetto, F.; Ballarin, R.; Tarantino, G.
abstract

Background: Hepatic caudatectomy has always been considered a challenging procedure, because of the complex anatomy and deep location of this segment. Herein we report the first case of a totally robotic isolated caudate-lobe liver resection ever performed for hydatid disease. Methods: A 55 year-old man was referred to our institution after diagnosis was made of a 5.6 cm hepatic lesion of the caudate lobe. Radiological suspicion was for hydatid disease. The patient underwent robotic-assisted hepatic caudatectomy. Results: The operative time was 280 min and the estimated blood loss was 200 ml. The postoperative course was uneventful. The drain was removed on post-operative day 3 and the patient was discharged on post-operative day 6. Conclusion: Robotic resection of the caudate lobe is a technically feasible procedure, which nevertheless requires high hepato-pancreato-biliary surgery skills, both in open an mini-invasive approaches. It provides several technical advantages in the field of mini-invasive surgery, yet assuring patient safety. Copyright © 2015 John Wiley & Sons, Ltd.

2016 - Vacuum-Assisted Closure Therapy in Patients Undergoing Liver Transplantation with Necessity to Maintain Open Abdomen [Articolo su rivista]
Assirati, G.; Serra, V.; Tarantino, G.; Aldrovandi, S.; Ballarin, R.; Magistri, P.; De Ruvo, N.; Di Benedetto, F
abstract

2015 - Effect of anti-oxidant agents in patients with hepatocellular diseases [Articolo su rivista]
Di Francia, R.; Rinaldi, L.; Troisi, A.; Di Benedetto, F.; Berretta, M.
abstract

2015 - ISOLATED CAUDATE LOBECTOMY FOR SPIEGEL LOBE NEOPLASMS [Articolo su rivista]
D'Amico, G; Tarantino, G; Serra, V; Serra, F; Ballarin, R; Di Benedetto, F
abstract

Introduction: Caudate lobe, or segment 1 of the liver, is the segment of the liver that occupies the space between the hilar plate and the retrohepatic vena cava. Its peculiar embryology accounts for the unique vascular and biliary anatomy. The location among three major vascular structures (the hepato-duodenal ligament, the vena cava and the hepatic veins cranially), together with its characteristic hypertrophy in case of increased portal system pressure, makes the caudate lobe as one of the most challenging liver segments. Caudate lobe resections for tumor may be performed as isolated segmental resections or associated to major hepatic resections, when other liver segments are involved. We describe here our 14-years experience of 7 cases of isolated caudate lobe resection for tumor.Patients and Methods: From October 2000 to December 2014 826 patients underwent liver resection at our institution, of which 286 (34.6%) minor resection (wedge resection, sub-segmental resection and segmental resection), 200 (24.2%) right hepatectomy, 260 (31.4%) left hepatectomy, 20 (2.4%) left trisegmentectomy and 60 (7.2%) patient right trisegmentectomy. Of those, 45 (8.3%) had a concomitant caudate lobe resection. In seven patients (0.8%), the tumor was confined to the caudate lobe and an isolated caudate lobe resection was performed. The indication was as follow: 2 patients had Hepatocellular carcinoma (HCC), 3 patients had metastasis (colorectal in two cases and from adrenal gland in one case), 1 adenoma, and one presented with a non-Hodgkin lymphoma. For these patients we analyzed intraoperative data, post operative course and survival.Results: Five (71.4%) out of 7 patients are still alive after a mean follow up of 8.4+/-5 years. Two patients died of disease recurrence after 7 months and 8 years, respectively. The mean operating time was 304.8+/-109.7 minutes and the mean estimated blood loss was 266.6+/-123.8 ml. There were no intra-operative or post-operative complication. The mean Intensive Care Unit stay was 1.2+/-0.7 days. Each lesion was localized into the Spiegel lobe, and each patient had at the pathology specimen only one nodule. In all cases the margins were free of tumor.Conclusions: Isolated caudate lobectomy is a difficult surgical procedure that may be associated with significant intra-operative bleeding and dangerous vascular and biliary injuries. In spite of these difficulties, this procedure can be considered the gold standard treatment for any lesions, benign or malignant, involving and confined to the Spiegel Lobe, especially when is crucial to preserve the remnant parenchyma.

2015 - LIVER RESECTION FOR HCC IN HIV-INFECTED PATIENTS: A SINGLE CENTER EXPERIENCE [Articolo su rivista]
D'Amico, G; Tarantino, G; Ballarin, R; Serra, V; Pecchi, A R; Guaraldi, G; Di Benedetto, F
abstract

HIV-infected patients now live longer and often have complications of liver disease, especially with hepatitis B or C virus co-infection. Hepatocellular carcinoma (HCC) is an increasing cause of mortality in HIV positive and negative individuals. There is a lack of consensus regarding the clinical presentation, treatment options, and outcome in HIV-infected patients with HCC. Unfortunately, HCC is frequently diagnosed at an advanced stage, and mortality continues to be very high. Earlier diagnosis, which may allow potentially curative therapy, is necessary. Liver resection is considered the most potentially curative treatment for HCC patients when liver transplantation is not an option or is not immediately accessible. The aim of this article was to describe our liver resection strategy, describing our experience, for HCC in HIV infected patients.

2015 - Neurological complications after liver transplantation as a consequence of immunosuppression: Univariate and multivariate analysis of risk factors [Articolo su rivista]
Rompianesi, G.; Montalti, R.; Cautero, N.; De Ruvo, N.; Stafford, A.; Bronzoni, C.; Ballarin, R.; De Pietri, L.; Di Benedetto, F.; Gerunda, G. E.
abstract

Neurological complications (NCs) can frequently and significantly affect morbidity and mortality of liver transplant (LT) recipients. We analysed incidence, risk factors, outcome and impact of the immunosuppressive therapy on NC development after LT. We analysed 478 LT in 440 patients, and 93 (19.5%) were followed by NCs. The average LOS was longer in patients experiencing NCs. The 1-, 3- and 5-year graft survival and patient survival were similar in patients with or without a NC. Multivariate analysis showed the following as independent risk factors for NC: a MELD score ≥20 (OR = 1.934, CI = 1.186-3.153) and an immunosuppressive regimen based on calcineurin inhibitors (CNIs) (OR = 1.669, CI = 1.009-2.760). Among patients receiving an everolimus-based immunosuppression, the 7.1% developed NCs, vs. the 16.9% in those receiving a CNI (P = 0.039). There was a 1-, 3- and 5-year NC-free survival of 81.7%, 81.1% and 77.7% in patients receiving a CNI-based regimen and 95.1%, 93.6% and 92.7% in those not receiving a CNI-based regimen (P < 0.001). In patients undergoing a LT and presenting with nonmodifiable risk factors for developing NCs, an immunosuppressive regimen based on CNIs is likely to result in a higher rate of NCs compared to mTOR inhibitors.

2015 - NEW ENTITIES IN THE TREATMENT OF HEPATOCELLULAR CARCINOMA: HIV-POSITIVE AND ELDERLY PATIENTS [Articolo su rivista]
Berretta, M; Di Francia, R; Di Benedetto, F; Tirelli, U
abstract

The hepatocellular carcinoma (HCC) is the most common primary cancer of the liver and, according to the WHO report, the fourth commonest cause of death. The incidence of HCC has been rising in developed western countries in the last two decades, along with the emergence of hepatitis C virus infection and to the rise of immigration rates from HBV-endemic countries. In addition, even though the incidence of HCC reaches its highest peak among persons over 65 years, an increased incidence among younger individuals has been noted in the last two decades both in USA and Europe. In the last decades two kinds of HCC patients are more interesting, for clinical characteristics, than typical patients with HCC: elderly and HIV-positive patients. In fact due to the increase of the life expectancy in many countries, HCC represents a new challenge in this particular setting of patients.

2015 - Post-transplantation hepatocellular carcinoma recurrence: Patterns and relation between vascularity and differentiation degree [Articolo su rivista]
Pecchi, Annarita; Besutti, Giulia; de Santis, Mario; DEL GIOVANE, Cinzia; Nosseir, Sofia; Tarantino, Giuseppe; DI BENEDETTO, Fabrizio; Torricelli, Pietro
abstract

Aim: To evaluate the relationship between hepatocellular carcinoma (HCC) vascularity and grade; to describe patterns and vascular/histopathological variations of post-transplantation recurrence. Methods: This retrospective study included 165 patients (143 men, 22 women; median age 56.8 years, range 28-70.4 years) transplanted for HCC who had a follow-up period longer than 2 mo. Pre-transplantation dynamic computed tomography or magnetic resonance examinations were retrospectively reviewed, classifying HCC imaging enhancement pattern into hypervascular and hypovascular based on presence of wash-in during arterial phase. All pathologic reports of the explanted livers were reviewed, collecting data about HCC differentiation degree. The association between imaging vascular pattern and pathological grade was estimated using the Fisher exact test. All follow-up clinical and imaging data were reviewed for evidence of recurrence. Recurrence rate was calculated and imaging features of recurrent tumor were collected, classifying early and late recurrences based on timing (< or ≥ 2 years after transplantation) and intrahepatic, extrahepatic and both intrahepatic and extrahepatic recurrences based on location. All intrahepatic recurrences were classified as hypervascular or hypovascular and the differentiation degree was collected where available. The presence of variations in imaging enhancement pattern and pathological grade between the primary tumor and the intrahepatic recurrence was evaluated and the association between imaging and histopatholgical variations was estimated by using the χ2 test. Results: Of the 163 patients with imaging evidence of viable tumor, 156 (95.7%) had hypervascular and 7 (4.3%) hypovascular HCC. Among the 125 patients with evidence of viable tumor in the explanted liver, 19 (15.2%) had grade 1, 56 (44.8%) grade 2, 40 (32%) grade 3 and 4 (3.2%) grade 4 HCC, while the differentiation degree was not assessable for 6 patients (4.8%). A significant association was found between imaging vascularity and pathological grade (P = 0.035). Post-transplantation recurrence rate was 14.55% (24/165). All recurrences occurred in patients who had a hypervascular primary tumor. Three patients (12.5%) experienced late recurrence; the location of the first recurrence was extrahepatic in 14 patients (58.3%), intrahepatic in 7 patients (29.2%) and both intrahepatic and extrahepatic in 3 patients (12.5%). Two patients had a variation in imaging characteristics between the primary HCC (hypervascular) and the intrahepatic recurrent HCC (hypovascular), while 1 patient had a variation of histopathological characteristics (from moderate to poor differentiation), however no association was found between imaging and histopathological variations. Conclusion: A correlation was found between HCC grade and vascularity; some degree of variability may exist between the primary and the recurrence imaging/histopathological characteristics, apparently not correlated.

2015 - ROBOTIC DISTAL PANCREATECTOMY FOR PANCREATIC LEIOMYOSARCOMA [Articolo su rivista]
Tarantino, G; Ballarin, R; Bonetti, L R; Di Benedetto, F
abstract

Objective: Primary leiomyosarcoma of the pancreas (PLMS) is an extremely rare tumour. Herein we report the first case of robotic distal pancreatectomy (DP) ever performed so far. Patiens and Methods: A 73-year-old woman was referred to our Institution after a diagnosis of pancreatic neoplasm was made. She underwent robotic assisted DP. Results: The patient was discharged to home in the fourth post-operative day. Immunohistochemical staining was positive for smooth muscle markers, with negative expression of epithelial and neural markers, thus confirming the diagnosis of high grade PLMS. Conclusions: Robotic DP combined good oncological results together with the advantages of minimally access surgery.

2015 - Total abdominal approach for postero-superior segments (7, 8) in laparoscopic liver surgery: a multicentric experience [Articolo su rivista]
Giuliani, A.; Aldrighetti, L.; Di Benedetto, F.; Ettorre, G. M.; Bianco, P.; Ratti, F.; Tarantino, G.; Santoro, R.; Felli, E.
abstract

Laparoscopic liver resections are frequently performed for peripheral lesions located in the antero-inferior segments. Resection of postero-superior segments is more demanding and dangerous than other segmentectomies, resulting in a longer operation time and increased blood loss. To reduce technical challenges, some authors advocated a modified surgical approach for these segments with the patient placed in the left lateral decubitus with the right arm suspended and suggested technical variations like the use of an additional intercostal trocar, the placement of one or two additional trans-thoracic trocars, a hand-assisted approach or a hybrid method with a median laparotomy. In the present series of 88 patients from four hepatobiliary centers with high volume of activity in Italy, a standard lithotomic position has been routinely used without the need for left lateral decubitus or semi-prone position and through abdominal wall without use of trans-thoracic trocars. This approach allows a more comfortable use of the Pringle maneuver that we used routinely in hepatic resection for PS segments; and, a very short time is needed for conversion, whenever it is required. In our series, laparoscopic resection of liver tumors located in the postero-superior segments of the liver with a total abdominal approach is technically feasible and safe with short-term results similar to other laparoscopic liver resections.

2014 - Absence of viable HCC in the native liver is an independent protective factor of tumor recurrence after liver transplantation [Articolo su rivista]
Montalti, Roberto; Mimmo, Antonio; Rompianesi, Gianluca; Di Gregorio, Carmela; Serra, Valentina; Cautero, Nicola; Ballarin, Roberto; Spaggiari, Mario; Tarantino, Giuseppe; D’Amico, Giuseppe; De Santis, Mario; De Pietri, Lesley; Troisi, Roberto I.; Gerunda, Giorgio E.; Di Benedetto, Fabrizio
abstract

BACKGROUND: Prognostic factors for hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) are still a matter of debate. The absence of viable tumor in the native liver, due to effectiveness of pre-LT locoregional treatment or liver resection, is an intriguing prognostic factor that had never been evaluated. METHODS: Between November 2000 and December 2011, 210 LTs were performed in patients with evidence of HCC and cirrhosis. RESULTS: Fifty-three (25.2%) patients did not show any evidence of active residual HCC in the native liver (Group NVH), whereas 157 (74.8%) patients showed viable HCC (Group VH). All patients in Group NVH were treated before LT with a multimodal approach combining transarterial chemoembolization, liver resection, radiofrequency ablation, percutaneous ethanol injection, or sorafenib, whereas, in Group VH, 110 of the 157 (70.1%) patients received bridging therapy (P&lt;0.001). HCC recurrence occurred in none of the patients in Group NVH (0%) and in 25 (15.9%) patients in Group VH (P=0.003). Liver resection was the most effective treatment in obtaining absence of HCC on liver explantation. The results of multivariate analysis showed that existence of pathologic HCC findings outside of the University of California-San Francisco criteria (P=0.001; odds ratio, 4; confidence interval, 1.7-9.2) and the presence of viable HCC (P=0.003; odds ratio, 5.9; confidence interval, 1.5-17.6) were independently associated with HCC recurrence. CONCLUSIONS: The histologic absence of viable HCC in the native liver after LT and morphologic criteria, due to the high effectiveness of pre-LT bridging treatments, is a highly positive prognostic factor against HCC recurrence after LT.

2014 - Intrahepatic blood flow redistribution after temporary occlusion of the middle hepatic vein during right lobe liver donation: Report of a case [Articolo su rivista]
Diago, T.; Quintini, C.; Di Benedetto, F.; Trenti, L.; Nassar, A.; Bertani, H.; Cautero, N.; Lauro, A.; Pinna, A. D.; Miller, C. M.
abstract

Introduction One of the critical factors that influence graft function after live donor liver transplantation is the presence or absence of global or sectorial liver congestion. Many authors advocate for routine middle hepatic vein (MHV) reconstruction because it is often difficult to determine when the MHV or one of its major branches have functional significance. Predictive tests to assess hemodynamic and functional significance of the MHV and its tributaries are still under study.Case Report We have described a novel intraoperative manipulation and Doppler ultrasonographic evaluation that led to the decision to include the MHV with the right lobe graft.

2014 - Long-term maintenance of sustained virological response in liver transplant recipients treated for recurrent hepatitis C [Articolo su rivista]
Ponziani, F. R.; Vigano, R.; Iemmolo, R. M.; Donato, M. F.; Rendina, M.; Toniutto, P.; Pasulo, L.; Morelli, M. C.; Burra, P.; Miglioresi, L.; Merli, M.; Di Paolo, D.; Fagiuoli, S.; Gasbarrini, A.; Pompili, M.; Belli, L.; Gerunda, G. E.; Marino, M.; Montalti, R.; Di Benedetto, F.; De Ruvo, N.; Rigamonti, C.; Colombo, M.; Rossi, G.; Di Leo, A.; Lupo, L.; Memeo, V.; Bringiotti, R.; Zappimbulso, M.; Bitetto, D.; Vero, V.; Colpani, M.; Fornasiere, E.; Pinna, A. D.; Morelli, M. C.; Bertuzzo, V.; De Martin, E.; Senzolo, M.; Ettorre, G. M.; Visco-Comandini, U.; Antonucci, G.; Angelico, M.; Tisone, G.; Giannelli, V.; Giusto, M.
abstract

Abstract BACKGROUND: The recurrence of hepatitis C viral infection is common after liver transplant, and achieving a sustained virological response to antiviral treatment is desirable for reducing the risk of graft loss and improving patients' survival. AIM: To investigate the long-term maintenance of sustained virological response in liver transplant recipients with hepatitis C recurrence. METHODS: 436 Liver transplant recipients (74.1% genotype 1) who underwent combined antiviral therapy for hepatitis C recurrence were retrospectively evaluated. RESULTS: The overall sustained virological response rate was 40% (173/436 patients), and the mean follow-up after liver transplantation was 11±3.5 years (range, 5-24). Patients with a sustained virological response demonstrated a 5-year survival rate of 97% and a 10-year survival rate of 93%; all but 6 (3%) patients remained hepatitis C virus RNA-negative during follow-up. Genotype non-1 (p=0.007), treatment duration &gt;80% of the scheduled period (p=0.027), and early virological response (p=0.002), were associated with the maintenance of sustained virological response as indicated by univariate analysis. Early virological response was the only independent predictor of sustained virological response maintenance (p=0.008). CONCLUSIONS: Sustained virological response achieved after combined antiviral treatment is maintained in liver transplant patients with recurrent hepatitis C and is associated with an excellent 5-year survival.

2014 - Radiofrequency vessel-sealing system versus the clamp-crushing technique in liver transection: Results of a prospective randomized study on 100 consecutive patients [Articolo su rivista]
Muratore, A.; Mellano, A.; Tarantino, G.; Marsanic, P.; De Simone, M.; Di Benedetto, F.
abstract

Background Liver transection is considered a critical factor influencing intra-operative blood loss. A increase in the number of complex liver resections has determined a growing interest in new devices able to 'optimize' the liver transection. The aim of this randomized controlled study was to compare a radiofrequency vessel-sealing system with the 'gold-standard' clamp-crushing technique. Methods From January to December 2012, 100 consecutive patients undergoing a liver resection were randomized to the radiofrequency vessel-sealing system (LF1212 group; N = 50) or to the clamp-crushing technique (Kelly group, N = 50). Results Background characteristics of the two groups were similar. There were not significant differences between the two groups in terms of blood loss, transection time and transection speed. In spite of a not-significant larger transection area in the LF1212 group compared with the Kelly group (51.5 versus 39 cm2, P = 0.116), the overall and 'per cm2' blood losses were similar whereas the transection speed was better (even if not significantly) in the LF1212 group compared with the Kelly group (1.1 cm2/min versus 0.8, P = 0.089). Mortality, morbidity and bile leak rates were similar in both groups. Conclusions The radiofrequency vessel-sealing system allows a quick and safe liver transection similar to the gold-standard clamp-crushing technique. © 2014 International Hepato-Pancreato-Biliary Association.

2014 - Results of salvage liver transplantation [Articolo su rivista]
Guerrini, Gian Piero; Gerunda, Giorgio Enrico; Montalti, R; Ballarin, Roberto; Cautero, Nicola; De Ruvo, N; Spaggiari, Mario; DI BENEDETTO, Fabrizio
abstract

BACKGROUND & AIMS: Salvage liver transplantation (SLT) is an attractive sequential strategy which combines liver resection (LR) for hepatocellular carcinoma (HCC), followed by liver transplant (LT) in the event of HCC recurrence or progressive liver deterioration. To compare the long-term results of SLT with primary liver transplant (PLT). METHODS: Between 2000 and 2011, 125 patients (72 transplantable) underwent LR and 226 underwent LT in our unit. The outcome of SLT was analysed in a two-step fashion: firstly, SLT (n = 28) was compared with PLT (n = 198), secondly an intention-to-treat analysis was performed on all transplantable HCC patients who underwent LR (LRT group = 72) compared to PLT (n = 198). RESULTS: The five-year overall survival (OS) was 65.4% vs. 49.2% (P = 0.63), and disease-free survival (DFS) was 89.7% vs. 80.6% (P = 0.31) for PLT and SLT respectively. Predictive factors for DFS after LT included HCC total diameter [hazard ratio (HR) 1.29 P = 0.003], alpha-foetoprotein (HR 1.002 P < 0.001) and number of HCC nodules (HR 1.317 P = 0.035), whereas viral hepatitis C positivity (HR 1.911 P = 0.03) and outside Up-to-seven criteria (HR 2.652 P < 0.001) were negative independent prediction factors of OS. Intention-to-treat analysis showed that OS at 5 years was improved in PLT vs. LRT (LRT n = 72 including SLT plus LR group) and was 69.4% vs. 42.2% (P < 0.004), with an additional increase in DFS (89.2% vs. 54.5% respectively P < 0.001). CONCLUSION: Salvage liver transplantation is a safe treatment strategy, as it does not impair long-term survival. At intention-to-treat analysis, PLT showed improved survival compared with LRT.

2014 - Topical hemostatic agents [Capitolo/Saggio]
Di Benedetto, F.; Tarantino, G.
abstract

Hemostasis in the operating theatre has always been an issue of fundamental importance in any surgical procedure. The amount of blood loss may greatly vary between different surgical procedures and depends on both surgical and non-surgical factors. Several different topical agents can be used to achieve or maintain hemostasis in surgical patients. Hemostatic agents can be divided into two categories: those that provide their mechanism of action on the clotting cascade in a biologically active manner (active agents) and those that act passively through contact activation and promotion of platelet aggregation (passive agents). These products are available in a wide range of devices and are nowadays accepted and extensively used in the vast majority of surgical specialties with appreciable results in terms of blood loss sparing.

2013 - Colorectal cancer in elderly patients: from best supportive care to cure [Articolo su rivista]
Berretta, Massimiliano; DI BENEDETTO, Fabrizio; Di Francia, Raffaele; Lo Menzo, Emanuele; Palmeri, Sergio; De Paoli, Paolo; Tirelli, Umberto
abstract

Colorectal cancer is one of the major causes of cancer mortality in the elderly population (median age at diagnosis of 71 years) in Western Countries. Moreover patients with metastatic disease are often elderly with significant co- morbidities. Unfortunately, elderly patients are often untreated and under-represented in clinical trials, even if most clinical trials that have included this setting of population have shown similar survival rates and toxicities to younger patients. Age itself should not be considered for candidacy to chemotherapy but it should be taken in consideration the great heterogeneity of co-morbidities present in the elderly population. Therefore, the best treatment strategy for elderly colorectal cancer patients has not yet been defined. Comprehensive Geriatric Assessment is recommended to evaluate the best strategy treatment and to reduce the adverse events. In fact, while fit elderly patients could receive the same therapeutic treatment as the younger counterpart, a palliative approach should be taken in consideration for frail elderly patients and for those with a short life expectancy.

2013 - Hepatocellular carcinoma: beyond the boundaries of age [Articolo su rivista]
DI BENEDETTO, Fabrizio; Tarantino, Giuseppe; Quintini, Cristiano; Tirelli, Umberto; Berretta, Massimiliano
abstract

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide, and the management of HCC has radically changed in recent years. Over the last few years, many elderly patients have been considered less amenable to effective treatments compared to younger patients, due to the accumulation of different diseases during their lives. This assumption has now been reviewed and some key points have been outlined such as the necessity of a careful selection of patients, which may lead to satisfactory results after the treatment of elderly patients with HCC. The purpose of this study was to make a comprehensive analysis of results from the literature concerning the multimodal treatment of HCC in elderly patients, analyzing the therapeutic options such as liver resection, ablative treatments, liver transplantation and targeted chemotherapy.

2013 - Multicenter Italian Experience in Liver Transplantation for Hepatocellular Carcinoma in HIV-Infected Patients [Articolo su rivista]
DI BENEDETTO, Fabrizio; Tarantino, Giuseppe; G., Ercolani; U., Baccarani; R., Montalti; N., De Ruvo; M., Berretta; G. L., Adani; M., Zanello; M., Tavio; Cautero, Nicola; U., Tirelli; Gerunda, Giorgio Enrico; Guaraldi, Giovanni; Pinna, Antonio Daniele
abstract

Abstract: Background. The aim of our work is to assess the clinical outcomes of liver transplantation (LT) for hepatocellular carcinoma (HCC) in HIV-coinfected patients. This is a multicenter study involving three Italian transplant centers in northern Italy: University of Modena, University of Bologna, and University of Udine. Patients and Methods. We compared 30 HIV-positive pants affected by HCC who underwent LT with 125 HIV-uninfected patients who received the same treatment from September 2004 to June 2009. At listing, there were no differences between HIV-infected and -uninfected patients regarding HCC features. Patients outside the University of California, San Francisco criteria (UCSF) were considered eligible for LT if a down-staging program permitted a reduction of tumor burden. Results. HIV-infected patients were younger, they were more frequently anti-HCV positive, and a higher number of HIV-infected patients presented a coinfection HBV-HCV. Pre-LT treatments (liver resection and or locoregional treatments) were similar between the two groups. Histological characteristics of the tumor were similar in patients with and without HIV infection. No differences were observed in terms of overall survival and HCC recurrence rates. Conclusion. LT for HCC is a feasible procedure and the presence of HIV does not particularly affect the post-LT outcome.

2013 - Multiple ways to manage portal thrombosis during liver transplantation: surgical techniques and outcomes [Articolo su rivista]
D'amico, Giuseppe; Tarantino, Giuseppe; Spaggiari, Mario; Ballarin, Roberto; Serra, Valentina; Rumpianesi, G; Montalti, R; De Ruvo, N; Cautero, Nicola; Begliomini, Bruno; Gerunda, Giorgio Enrico; Di Benedetto, Fabrizio
abstract

Portal vein thrombosis (PVT) is a well-recognized complication of chronic liver disease with a prevalence ranging from 1% to 16%. MATERIALS AND METHODS: We performed a retrospective review of 447 consecutive patients who underwent liver transplantation (OLT) between October 2000 and December 2011 comparing 51 recipients with PVT (study group) with 399 without PVT (control group). The aim of this study was to determine the impact of pre-existent PVT on the surgical procedure, to identify specific preventable perioperative complications, and based on our studies and other works, to determine whether this group of patients are acceptable candidates for OLT. RESULTS: Among the 51 patients with PVT, 44 showed partial and 7 complete thrombosis. In 47 cases, we performed a thromboendovenectomy. There were six anastomoses at the confluence of the superior mesenteric vein (SMV) and one, with a venous graft interposition. In four complete thrombosis recipients we performed an extra-anatomic by pass between the main trunk of the SMV and the donor portal vein. Compared with the control group, regarding preoperative characteristics, PVT patients were older at the time of transplantation (P = .001) and had a higher use of TIPS (P = .02). The operative characteristics showed a longer warm ischemia time in the PVT group (46.9 ± 22.5 vs 39.3 ± 15 min; P = .004). There were significant differences in postoperative evaluations, nor in the complication rates. Overall survivals at 10 years were similar: 61.7% versus 65.3%; (P = .9). CONCLUSION: Although PVT was associated with greater operative complexity, it had no influence on postoperative complications or overall survival.

2013 - Onco-surgical management of colo-rectal liver metastases in older patients: a new frontier in the 3rd millennium [Articolo su rivista]
DI BENEDETTO, Fabrizio; D'Amico, Giuseppe; Spaggiari, Mario; Tirelli, Umberto; Berretta, Massimiliano
abstract

Colorectal cancer (CRC) is one the most common malignant tumors in industrialized countries today. Over half of all cancers are currently diagnosed in elderly patients, and 76% of all colorectal cancer patients are diagnosed between 65 and 85 years old. Elderly patients are less likely to undergo curative surgery, and less likely to be offered the option of metastasectomy when colorectal liver metastases (CLM) are present. Hepatic resection has become the standard care for the treatment of isolated CLM. However, in studies reporting resection of CLM only 8-20% of the patients are older than 70 years. When balancing the benefits of surgical resection of liver metastases against the potential risks of surgery, many clinicians are still reluctant to advise in favor of surgical treatment in the elderly. Factors other than age should also be considered when evaluating surgical risk in the elderly, for example, conditions such as heart disease and diabetes have been shown to induce life-threatening postoperative complications. Age alone need not be a contraindication to aggressive surgical therapy in this group, rather, appropriate selection criteria based on tumor characteristics and general medical fitness, similar to those used for younger patients, should be applied.

2013 - Sorafenib for the treatment of unresectable hepatocellular carcinoma in HIV-positive patients [Articolo su rivista]
Berretta, M.; Di Benedetto, F.; Dal Maso, L.; Cacopardo, B.; Nasti, G.; Facchini, G.; Bearz, A.; Spina, M.; Garlassi, E.; De Re, V.; Fiorica, F.; Lleshi, A.; Tirelli, U.
abstract

Few data are available on the safety and efficacy of sorafenib in HIV-infected patients with unresectable hepatocellular carcinoma (HIV-u-HCC) and concomitant highly active antiretroviral therapy (HAART). Between July 2007 and October 2010, 27 consecutive HIV-u-HCC patients were treated with sorafenib and concomitant HAART within the Gruppo Italiano Cooperativo AIDS e Tumori (GICAT). Three patients achieved a partial response, 12 achieved a stable disease, and 12 showed progression. The median time to progression and overall survival was 5.1 (range 0.5-13.3) and 12.8 (range 1.1-23.5) months, respectively. Grades 3-4 toxicities included diarrhea (four patients, 14.8%), hypertension (three patients, 11%), and hand-and-foot skin reaction (four patients, 14.9%). Most drug-related side effects were low grade and manageable. This retrospective study shows favorable survival data among HIV-u-HCC patients treated with sorafenib together with a reasonable safety profile. © 2013 Wolters Kluwer Health Lippincott Williams &amp; Wilkins.

2013 - Successful liver transplantation in a patient with splanchnic vein thrombosis and pulmonary embolism due to polycythemia vera with Jak2v617f mutation and heparin-induced thrombocytopenia. [Articolo su rivista]
Biagioni, E; Pedrazzi, Paola; Marietta, M; DI BENEDETTO, Fabrizio; Villa, Erica; Luppi, Mario; Girardis, Massimo
abstract

Heparin-induced thrombocytopenia (HIT) is a rare complication of heparin treatment resulting in a severe acquired thrombophilic condition with an associated mortality of about 10 %. We report the first case of successful urgent liver transplantation (LT) in a patient with end-stage liver disease due to a Budd-Chiari syndrome, portal vein thrombosis and pulmonary embolism due to acquired thrombophilia associated to polycythemia vera carrying JAK2V617F gene mutation and HIT in the acute phase. Lepirudin was used to provide anticoagulation in the LT perioperative period that was performed without haemorrhagic and thrombotic complications despite the donor received heparin during liver explantation.

2013 - Treatment of wounds colonized by multidrug resistant organisms in immune-compromised patients: a retrospective case series. [Articolo su rivista]
Pignatti, Marco; Gerunda, Giorgio Enrico; G., Rompianesi; N. D., Ruvo; DI BENEDETTO, Fabrizio; M., Codeluppi; D., Bonucchi; L., Pacchioni; P., Loschi; C., Malaventura; DE SANTIS, Giorgio
abstract

Immune-compromised patients incur a high risk of surgical wound dehiscence and colonization by multidrug resistant organisms. Common treatment has been debridement and spontaneous secondary healing.All immune-compromised patients referred to our Institution between March 1, 2010 and November 30, 2011 for dehiscent abdominal wounds growing multidrug resistant organisms were treated by serial wound debridements and negative pressure dressing. They were primarily closed, despite positive microbiological cultures, when clinical appearance was satisfactory.Nine patients were treated by direct wound closure, five had been treated previously by secondary intention healing.According to our results, fast healing can be safely obtained by closure of a clinically healthy wound, despite growth of multidrug resistant organisms, even in immune-compromised patients.

2012 - Aseptic Osteonecrosis: A Newly Diagnosed Complication in HIV-Infected Patients Undergoing Liver Transplantation. [Articolo su rivista]
Cocchi, Stefania; Franceschini, Erica; Meschiari, Marianna; Codeluppi, M; Rompianesi, Gianluca; DI BENEDETTO, Fabrizio; Gerunda, Giorgio Enrico; Mussini, Cristina; Guaraldi, Giovanni
abstract

Aseptic osteonecrosis: a newly diagnosed complication in HIV-infected patients undergoing liver transplantation

2012 - Banked Depopulated Vena Cava Homograft: A New Strategy to Restore Caval Continuity [Articolo su rivista]
DI BENEDETTO, Fabrizio; Giuseppe, D'Amico; Roberto, Montalti; Roberto, Ballarin; Giuseppe, Tarantino; Pecchi, Annarita; Gerunda, Giorgio Enrico
abstract

Non disponibile

2012 - Early use of mammalian target of rapamycin inhibitors is an independent risk factor for incisional hernia development after liver transplantation. [Articolo su rivista]
Montalti, R.; Mimmo, A.; Rompianesi, Gianluca; Serra, Valentina; Cautero, Nicola; Ballarin, Roberto; Ruvo, N. D.; Gerring, R. C.; Gerunda, Giorgio Enrico; DI BENEDETTO, Fabrizio
abstract

Incisional hernias (IHs) are common complications after liver transplantation (LT) with a reported incidence of 1.7\% to 34.3\%. The purpose of this retrospective study was to evaluate the risk factors for IH development after LT with a focus on the role of immunosuppressive therapy during the first month after LT. We analyzed 373 patients who underwent LT and divided them into 2 groups according to their postoperative course: an IH group (121 patients or 32.4\%) and a no-IH group (252 patients or 67.6\%). A univariate analysis demonstrated that the following were risk factors related to IH development: male sex (P = 0.03), a body mass index ≥ 29 kg/m(2) (P = 0.005), LT after 2004 (P = 0.02), a Model for End-Stage Liver Disease (MELD) score ≥ 22 (P = 0.01), and hepatitis B virus infection (P = 0.01). The highest incidence of IHs was found in patients treated with mammalian target of rapamycin (mTOR) inhibitors (54.5\%, P = 0.004). A multivariate analysis revealed male sex (P = 0.03), a pretransplant MELD score ≥ 22 (P = 0.04), and the use of mTOR inhibitors (P = 0.001) to be independent risk factors for IHs after LT. In conclusion, immunosuppressive therapy with mTOR inhibitors is an important independent risk factor for IH development after LT. To reduce the incidence of IHs, mTOR inhibitors should be avoided until the fourth month after LT unless their use is deemed to be strictly necessary.

2012 - Immunological advantages of everolimus versus cyclosporin A in liver-transplanted recipients, as revealed by polychromatic flow cytometry. [Articolo su rivista]
Roat, Erika; DE BIASI, Sara; Bertoncelli, Linda; Rompianesi, Gianluca; Nasi, Milena; Gibellini, Lara; Pinti, Marcello; DEL GIOVANE, Cinzia; A., Zanella; DI BENEDETTO, Fabrizio; Gerunda, Giorgio Enrico; Cossarizza, Andrea
abstract

Several immunosuppressive drugs with different mechanisms of action are available to inhibit organ rejection after transplant. We analyzed different phenotypic and functional immunological parameters in liver-transplanted patients who received cyclosporin A (CsA) or Everolimus (Evr). In peripheral blood mononuclear cells (PBMC) from 29 subjects receiving a liver transplant and treated with two different immunosuppressive regimens, we analyzed T cell activation and differentiation, regulatory T cells (Tregs) and Tregs expressing homing receptors such as the chemokine receptor CXCR3. T cell polyfunctionality was studied by stimulating cells with the superantigen staphylococcal enterotoxin B (SEB), and measuring the simultaneous production of interleukin (IL)-2 and interferon (IFN)-γ, along with the expression of a marker of cytotoxicity such as CD107a. The analyses were performed by polychromatic flow cytometry before transplantation, and at different time points, up to 220 days after transplant. Patients taking Evr had a higher percentage of total CD4⁺ and naïve CD4⁺ T cells than those treated with CsA; the percentage of CD8⁺ T cells was lower, but the frequency of naïve CD8⁺ T cells higher. Patients taking Evr showed a significantly higher percentage of Tregs, and Tregs expressing CXCR3. After stimulation with SEB, CD8⁺ T cells from Evr-treated patients displayed a lower total response, and less IFN-γ producing cells. The effects on the immune system, such as the preservation of the naïve T cell pool and the expansion of Tregs (that are extremely useful in inhibiting organ rejection), along with the higher tolerability of Evr, suggest that this drug can be safely used after liver transplantation, and likely offers immunological advantages.

2012 - Is advanced hepatocellular carcinoma amenable of cure by liver transplantation with sorafenib as a neoadjuvant approach plus m-TOR inhibitors monotherapy? [Articolo su rivista]
DI BENEDETTO, Fabrizio; M., Berretta; N. D., Ruvo; G., Tarantino; G., D'Amico; R., Ballarin; R. M., Iemmolo; Gerunda, Giorgio Enrico
abstract

not available

2012 - Laparoscopic radiofrequency ablation in the caudate lobe for hepatocellular carcinoma before liver transplantation [Articolo su rivista]
Di Benedetto, F; Tarantino, G; Montalti, R; Ballarin, R; D'Amico, G; Di Sandro, S; Gerunda, Ge.
abstract

The caudate lobe, because of its location and its highly unpredictable vascular anatomy, is one of the most surgical challenging segment of the liver. Hepatocellular carcinoma (HCC) of the caudate lobe in cirrhotic patients is not easily amenable to surgical resection. In order to treat HCC and to down-stage these patients within accepted criteria for liver transplantation (LT), laparoscopic radiofrequency ablation (RFA) can be performed.We present three cases of laparoscopic RFA for caudate lobe HCC. All three patients were successfully treated with laparoscopic RFA. The computed tomography scans 1 month postsurgery revealed complete necrosis of the lesion. No postoperative complications occurred, and all patients had a short postoperative stay. All three patients underwent, thereafter, LT from a deceased donor.Laparoscopic RFA is the treatment of choice in patients with HCC who could be scheduled for LT. Furthermore, a laparoscopic technique with an accurate ultrasound examination of liver parenchyma can allow for a complete exclusion of hepatic lesions undetectable at the preoperative imaging and provides the minimal onset of adhesions, both approaches that are extremely useful in patients undergoing liver transplantation.

2012 - Meso-Pancreatectomy: New Surgical Technique for Wirsung Reconstruction [Articolo su rivista]
Di Benedetto, Fabrizio; D'Amico, Giuseppe; Ballarin, Roberto; Tarantino, Giuseppe; Cautero, Nicola; Pecchi, Anna; Gerunda, Giorgio Enrico
abstract

Nessuno

2012 - Pancreatic Cancer in HIV-Positive Patients: A Clinical Case-Control Study. [Articolo su rivista]
Zanet, E.; Berretta, M.; DI BENEDETTO, Fabrizio; Talamini, R.; Ballarin, Roberto; Nunnari, G.; Berretta, S.; Ridolfo, A.; Lleshi, A.; Zanghì, A.; Cappellani, A.; Tirelli, U.
abstract

OBJECTIVES: Pancreatic cancer (PC) is the fourth and fifth most common cause of cancer-related death among men in United States and in Europe, respectively. No data are available for HIV-positive patients. The aim of this study was to investigate and to compare clinical presentation and outcome between HIV-positive and HIV-negative PC patients. METHODS: From April 1988 to June 2010, the Italian Cooperative Group on AIDS and Tumors identified 16 cases of HIV-positive PC patients. Each HIV-positive patient from our institution was randomly matched (ratio 1:2) with HIV-negative patients (32 controls) based on sex and year of PC diagnosis. Differences in clinical presentation, treatment, and overall survival were assessed. RESULTS: At multivariate analysis, HIV-positive patients compared with HIV-negative patients had a higher risk of an unfavorable performance status (PS ≥2) and a younger age (<50 years) at cancer diagnosis. At multivariate analysis, HIV-positive status and PS of 2 or greater were the only 2 features that significantly reduced PC patients' survival. CONCLUSIONS: Our data show, for the first time, that HIV-positive PC patients, compared with HIV-negative patients, are younger at cancer diagnosis. Furthermore, they share a more unfavorable PS and a shorter survival.

2012 - Role of intraoperative ultrasonography for pancreatic schwannoma. [Articolo su rivista]
DI BENEDETTO, Fabrizio; Ballarin, Roberto; Spaggiari, Mario; Pecchi, Annarita; Gerunda, Giorgio Enrico
abstract

Non available

2011 - Combined liver-kidney transplantation in patients infected with human immunodeficiency virus [Articolo su rivista]
DI BENEDETTO, Fabrizio; D'Amico, Giuseppe; Ruvo, N. D.; Cocchi, Stefania; Montalti, R.; Cautero, Nicola; Guerrini, G. P.; Ballarin, Roberto; Spaggiari, Mario; Tarantino, Giuseppe; Baisi, B.; Cappelli, Gianni; Codeluppi, M.; Gerunda, Giorgio Enrico
abstract

Although human immunodeficiency virus (HIV) infection has been a major global health problem for almost 3 decades, with the introduction of highly active antiretroviral therapy in 1996 and effective prophylaxis and management of opportunistic infections, mortality from acquired immunodeficiency syndrome has decreased markedly. In developed countries, this condition is now being treated as a chronic condition. As a result, rates of morbidity and mortality from other medical conditions leading to end-stage liver, kidney, and heart disease are steadily increasing in individuals with HIV. Because the definitive treatment for end-stage organ failure is transplantation, the demand for it has increased among HIV-infected patients. For these reasons, many transplant centers have eliminated HIV infection as a contraindication to transplantation, as a result of better patient management and demand.

2011 - Endovenous 808-nm diode laser occlusion of perforating veins and varicose collaterals: A prospective study of 482 limbs [Articolo su rivista]
Corcos, L.; Pontello, D.; De Anna, D.; Dini, S.; Spina, T.; Barucchello, V.; Carrer, F.; Elezi, B.; Di Benedetto, F.
abstract

BACKGROUND: Endovenous laser ablation (EVLA) was performed in the treatment of great and small saphenous veins (GSVs, SSVs), perforating veins (PVs), and varicose collaterals (VCs). OBJECTIVE To verify the outcome in PVs and VCs. MATERIALS AND METHODS Four hundred eighty-two limbs of 306 patients were studied. EVLA was performed on 167 GSVs, 52 SSVs, and 534 PVs of 303 limbs and on VCs of 467 limbs; 133 GSVs were stripped, 300 of saphenofemoral junctions (SFJs) and 45 saphenopopliteal junctions (SPJs) were interrupted. Limbs were selected using duplex ultrasound examination and photographs; PVs-VCs diameter (&lt;4 mm) and VC length were measured. EVLA was performed using a 808-nm diode laser, 0.6-mm fibers, continuous emission, 4 to 10 W, and 10 to 20 J/cm. Follow-up on 467 limbs occurred over a mean 27.5 months (range 3 months to 6 years); 98 limbs were followed up for longer than 4 years. RESULTS Operating time range from 10 to 30 minutes per limb. Blood vaporization, thrombosis, fibrosis, and atrophy prevailed in PVs and in the large VCs (&gt;4 mm) and massive coagulation in the smaller (&lt;4 mm). High rate of occlusion was seen, with different rates of patent PV-VC mainly in diameter &gt;6 mm. Thirty-nine out of 511 patent PVs (7.6%) and 96 out of 778 VCs (12-13%) were re-treated using EVLA or foam sclerotherapy. Minor complications occurred in 88 of the 778 (11%). CONCLUSIONS EVLA of PVs and VCs is effective and faster than surgery in 2- to 6-mm PVs and VCs using an 808-nm diode laser. © 2011 by the American Society for Dermatologic Surgery, Inc.

2011 - Fusarium verticillioides fungemia in a liver transplantation patient: successful treatment with voriconazole [Articolo su rivista]
S., Cocchi; M., Codeluppi; C., Venturelli; A., Bedini; Grottola, Antonella; W., Gennari; F., Cavrini; Di Benedetto, Fabrizio; N., De Ruvo; F., Rumpianesi; Gerunda, Giorgio Enrico; Guaraldi, Giovanni
abstract

Fusarium is an opportunistic fungal pathogen which is emerging as a significant cause of morbidity and mortality in immunocompromised hosts. We present a rare case of F. verticillioides fungemia that occurred in a patient who underwent a second orthotopic liver transplantation for chronic rejection and completely responded to treatment with voriconazole.

2011 - Hepatocellular Carcinoma in HIV-infected Patients: Check Ealy, Treat Hard [Articolo su rivista]
M., Berretta; Garlassi, Elisa; B., Cacopardo; A., Cappellani; Guaraldi, Giovanni; S., Cocchi; P., de Paoli; A., Lleshi; I., Izzi; A., Torresin; P., Di Gangi; Pietrangelo, Antonello; M. C., Ferrari; A., Beraz; S., Berretta; G., Nasti; DI BENEDETTO, Fabrizio; L., Balestreri; U., Tirelli; Ventura, Paolo
abstract

Purpose. Hepatocellular carcinoma (HCC) is an increasingcause of mortality in HIV-infected patients inthe highly active antiretroviral therapy (HAART) era.The aims of this study were to describe HCC tumorcharacteristics and different therapeutic approaches, toevaluate patient survival time from HCC diagnosis, andto identify clinical prognostic predictors in patients withand without HIV infection.Patients and Methods. A multicenter observationalretrospective comparison of 104 HIV-infected patientsand 484 uninfected patients was performed in four Italiancenters. HCC was staged according to the BarcelonaClinic Liver Cancer (BCLC) criteria.Results. Tumor characteristics of patients with andwithout HIV were significantly different for age, EasternCooperative Oncology Group performance status(PS) score <1, and etiology of chronic liver disease. Despitethe similar potentially curative option rate and better BCLC stage at diagnosis, the median survivaltime was significantly shorter in HIV patients. HIVpatients were less frequently retreated at relapse.Independent predictors of survival were: BCLC stage,potentially effective HCC therapy, tumor dimension <3cm, HCC diagnosis under a screening program, HCC recurrence,and portal vein thrombosis. Restricting the analysisto HIV patients only, all positive prognostic factorswere confirmed together with HAART exposure.Conclusion. This study confirms a significantlyshorter survival time in HIV HCC patients. The lessaggressive retreatment at recurrence approach does notbalance the benefit of younger age and better BCLCstage and PS score of HIV patients. Thus, consideringthe prognosis of HIV HCC patients, effective screeningtechniques, programs, and specific managementguidelines are urgently needed.

2011 - Immunosuppressive strategies in liver transplantation in hiv co-infected patients: university of modena experience. Transplant international [Abstract in Rivista]
DI BENEDETTO, Fabrizio; Tarantino, Giuseppe; D'Amico, Giuseppe; De Ruvo, N; Cautero, N; Montalti, R; Guerrini, Gp; Ballarin, R; Spaggiari, Mario; Guaraldi, Giovanni; Gerunda, Giorgio Enrico
abstract

Highly active antiretroviral therapy in the last decade increased the survival rates in HIV positive patients, determing at the same time a higer number of HIV patients suffering from liver-related disease. Liver tranplantation is the only curative treatment for end-stage liver disease associated or not associated with HCC.

2011 - Liver resection for colorectal metastases in older adults: A paired matched analysis [Articolo su rivista]
Di Benedetto, F.; Berretta, M.; D'Amico, G.; Montalti, R.; Ruvo, N. D.; Cautero, N.; Guerrini, G. P.; Ballarin, R.; Spaggiari, M.; Tarantino, G.; Di Sandro, Stefano; Pecchi, A.; Luppi, G.; Gerunda, G.
abstract

To assess the safety and long-term results of hepatic resection of colorectal liver metastases (CLM) in older adults.Case-control.Single liver and multivisceral transplant center.Individuals with CLM: 32 aged 70 and older (older group) and 32 younger than 70 (younger group) matched in a 1:1 ratio according to sex, primary tumor site, liver metastases at diagnosis, number of metastases, maximum tumor size, infiltration of cut margin, type of hepatic resection, and hepatic resection timing.Postoperative complications and survival rates.There was no significant difference in preoperative clinical findings between the two study groups. The incidence of cumulative postoperative complications was similar in the older (28.1%) and younger (34.4%) groups (P&nbsp;=&nbsp;.10). One-, 3-, and 5-year disease-free survival rates were 57.6%, 32.9%, and 16.4%, respectively, in the younger group and 67.9%, 29.2%, and 19.5%, respectively, in the older group (P&nbsp;=&nbsp;.72). One-, 3-, and 5-year participant survival rates were 84.1%, 51.9%, and 33.3%, respectively, in the older group and 93.6%, 63%, and 28%, respectively, in the younger group (P&nbsp;=&nbsp;.50).Resection of colorectal liver metastases in older adults can be performed with low mortality and morbidity and offers a long-time survival advantage to many of these individuals. Based on the results of this case-control study, older adults should be considered for surgical treatment whenever possible.

2011 - Liver Transplantation for Hepatocellular Carcinoma in HIV Co-Infected Patients: A Single Centre Experience. [Abstract in Rivista]
DI BENEDETTO, Fabrizio; Tarantino, Giuseppe; De Ruvo, N; Cautero, N; Montalti, R; Guerrini, Gp; Ballarin, R; Spaggiari, Mario; Serra, Valentina; Guaraldi, Giovanni; Gerunda, Giorgio Enrico
abstract

HCC is the leading cause of death aong patients with cirrhosis. HIV positive patients are likely to have hepatitis B and/or C virus co-infection because of wxposure to common risk factors. There are several reports that oulined a more aggressive course in HIV positive patients with respect to HCC. The aim of our study was to assess the outcome of liver tranplantation in this setting of patients.

2011 - Liver transplantation in older adults: our point of view. [Articolo su rivista]
Ballarin, Roberto; Montalti, R.; Spaggiari, Mario; Cautero, Nicola; Ruvo, N. D.; Guerrini, G. P.; Rompianesi, Gianluca; Longo, C.; Gerunda, Giorgio Enrico; DI BENEDETTO, Fabrizio
abstract

Not available

2011 - Long-term follow-up and outcome of liver transplantation from anti-hepatitis C virus-positive donors: a European multicentric case-control study. [Articolo su rivista]
Ballarin, Roberto; Cucchetti, A.; Spaggiari, Mario; Montalti, R.; DI BENEDETTO, Fabrizio; Nadalin, S.; Troisi, R. I.; Valmasoni, M.; Longo, C.; Ruvo, N. D.; Cautero, Nicola; Cillo, U.; Pinna, A. D.; Burra, P.; Gerunda, Giorgio Enrico
abstract

The growing prevalence of hepatitis C virus (HCV) infection in the general population has resulted in an increased frequency of potential organ donors that carry the virus. Given the significant disparity between organ supply and demand for transplantation, it becomes essential to consider whether livers from anti-HCV-positive donors may be considered suitable for transplantation.Based on a multicenter European database, 694 patients with HCV-related cirrhosis underwent liver transplantation and 11\% of them received the graft from anti-HCV-positive donors. Of this group, we selected 63 patients (study group) and, after a 1:1 case-control approach, compared them with 63 patients that received an anti-HCV-negative donor graft (control group). Only grafts with preperfusion liver biopsy results with a fibrosis score of not more than 1 were used for transplantation.Patients who received anti-HCV-positive grafts had a cumulative survival rate of 83.6\% and 61.7\% at 1 and 5 years, respectively, vs. 95.1\% and 68.2\% for the control group. In comparing overall patient and graft survival, there was no statistically significant difference between the two groups (P=0.22 and 0.11). Recurrence of hepatitis C tended to be more rapid in the group of patients who received anti-HCV-positive grafts, although it did not reach statistical significance (P=0.07).We do not recommend the indiscriminate use of anti-HCV-positive donors, especially if HCV-RNA positive, as the use of this kind of graft could be linked to an advanced stage of fibrosis, the main risk factor we observed for earlier hepatitis C recurrence.

2011 - Pancreatic metastases from renal cell carcinoma: the state of the art. [Articolo su rivista]
Ballarin, Roberto; Spaggiari, Mario; Cautero, N.; Ruvo, N. D.; Montalti, R.; Longo, C.; Pecchi, Annarita; Giacobazzi, Patrizia; Marco, G. D.; D'Amico, Giuseppe; Gerunda, Giorgio Enrico; DI BENEDETTO, Fabrizio
abstract

Pancreatic metastases are rare, with a reported incidence varying from 1.6\% to 11\% in autopsy studies of patients with advanced malignancy. In clinical series, the frequency of pancreatic metastases ranges from 2\% to 5\% of all pancreatic malignant tumors. However, the pancreas is an elective site for metastases from carcinoma of the kidney and this peculiarity has been reported by several studies. The epidemiology, clinical presentation, and treatment of pancreatic metastases from renal cell carcinoma are known from single-institution case reports and literature reviews. There is currently very limited experience with the surgical resection of isolated pancreatic metastasis, and the role of surgery in the management of these patients has not been clearly defined. In fact, for many years pancreatic resections were associated with high rates of morbidity and mortality, and metastatic disease to the pancreas was considered to be a terminal-stage condition. More recently, a significant reduction in the operative risk following major pancreatic surgery has been demonstrated, thus extending the indication for these operations to patients with metastatic disease.

2011 - Primary squamous cell carcinoma of the liver associated with Caroli's disease: a case report. [Articolo su rivista]
Spaggiari, Mario; DI BENEDETTO, Fabrizio; Ballarin, Roberto; Losi, L.; Cautero, Nicola; Ruvo, N. D.; Montalti, R.; Guerrini, Gian Piero; Gerunda, Giorgio Enrico
abstract

Not available

2011 - Role of chemoembolization as a rescue treatment for recurrence of resected hepatoblastoma in adult patients [Articolo su rivista]
Di Benedetto, F; Di Sandro, S; D’Amico, G; De Santis, M; Gerunda, Ge.
abstract

2011 - Role of magnetic resonance imaging in the detection of anastomotic biliary strictures after liver transplantation. [Articolo su rivista]
Pecchi, A.; Santis, M. D.; Gibertini, M. C.; Tarantino, G.; Gerunda, Giorgio Enrico; Torricelli, Pietro; DI BENEDETTO, Fabrizio
abstract

Biliary complications after orthotopic liver transplantation (OLT) are the principal cause of morbidity and graft dysfunction, ranging in incidence from 5.8\% to 30\% of cases. Biliary strictures are the most frequent type of late complication. The aim of this study was to evaluate the role of magnetic resonance cholangiography (MRC) to detect biliary anastomotic strictures among patients undergone OLT with abnormal liver function tests.One hundred twenty-one of 300 patients who underwent OLT were evaluated by MRC for clinically suspected anastomotic biliary strictures. In all patients, we performed various precholangiographic sequences including T1- and T2-weighted and MRC (radial SE 2D and SS-TSE 3D). Magnetic resonance imaging findings were subdivided as absence or presence of an anastomotic stricture. Diagnostic confirmation was obtained by endoscopic retrograde cholangiography (n=32), percutaneous transhepatic cholangiography (n=21) or surgical treatment (n=18).MRC detected 56 anastomotic biliary strictures, 53 of which were confirmed by other imaging modalities. MRC showed two false-negative cases and three false-positive cases. The sensitivity, specificity, positive and negative predictive values, and accuracy of MRC to detect biliary strictures were 96\%, 96\%, 95\%, 97\%, and 96\%, respectively.MRC proved to be a reliable noninvasive technique to visualize the biliary anastomosis and depict biliary strictures after OLT. MRC should be used when a biliary anastomotic stricture is suspected in an OLT patient.

2011 - Sorafenib before liver transplantation for hepatocellular carcinoma: risk or give up [Articolo su rivista]
DI BENEDETTO, Fabrizio; Tarantino, Giuseppe; Roberto, Montalti; Ballarin, Roberto; D'Amico, Giuseppe; Massimiliano, Berretta; Giorgio Enrico, Gerunda
abstract

Dear Sirs, We read with interest the article by Truesdale et al. [1] regarding their experience in the use of sorafenib before liver transplantation (LT) in patients with hepatocellular carcinoma (HCC). The authors compare ten patients who were administered sorafenib during waiting time for LT with twenty-three patients to whom the drug was not given. No difference in terms of overall and HCC recurrence-free survival was seen between the two groups. Indeed a higher incidence of biliary complications (67% vs. 17%) and acute cellular rejections (67% vs. 22%) was observed in the first group. The authors assume that the higher amount of complications is secondary to the use of sorafenib because of its main effect in inhibiting the vascular endothelial growth factor (VEGFR), reducing the resistance to apoptosis of cholangiocytes and thus both hindering the integrity of biliary vascularization and altering the immune pathway leading to cellular rejection. However, some major issues arise reading this paper: the authors do not specify the inclusion criteria for the use of sorafenib, the extension of the tumour burden before LT, the number of locoregional treatments before the drug was given and in general the efficacy of down-sizing procedures in this group of patients. An interesting matter of debate is the time to stop the administration of sorafenib. Infact the authors assert that the drug was stopped on the day of LT. In our experience [2], it seems not to be safe to continue with the administration of the drug until the day of LT: although there is no international agreement about this point [2–5], we usually interrupt the drug at least 3 weeks before a surgical procedure such as LT, because of the increased risk of bleeding of impaired wound healing and of liver dysfunction in the perioperative period in this setting of patients. Another intriguing issue is that doubtlessly sorafenib cannot still be considered nowadays in the group of the standard down-staging procedures of HCC in terms of safety and cost–effectiveness, but it should be reserved to the patients with advanced HCC traditionally treated with locoregional therapies/hepatic resection in whom sorafenib plays as important role in bringing them within the accepted criteria for LT with HCC. So as to exploit as much as possible the potential of the drug, we believe that sorafenib should not be reserved to patients with advanced HCC to whom any other curative treatment is not possible, but it should be offered also to a different setting of patients such as young patients outside standard criteria to LT. In the future, the challenge will be to break the Damocles sword of medical therapies for HCC, until now no effective therapy exists. The integration of sorafenib in the medical practice and its fully comprehension may permit the best management of these patients as possible

2011 - The Impact of Human Immunodeficiency Virus Infection in Liver Transplantation for Hepatocellular Carcinoma [Articolo su rivista]
DI BENEDETTO, Fabrizio; Giuseppe, Tarantino; Roberto, Montalti; Giuseppe, D’Amico; Stefania, Cocchi; Gerunda, Giorgio Enrico
abstract

Non disponibile

2011 - Transplantation of a fresh cadaveric iliac homograft after celiac artery aneurysmectomy. [Articolo su rivista]
C., Quintini; DI BENEDETTO, Fabrizio; A. D., Pinna
abstract

The authors describe a case of a 34-year-old woman who presented to the ER with acute epigastric pain caused by an 8-cm celiac artery aneurysm. The patient underwent total aneurysmectomy, distal splenopancreasectomy, and reconstruction of the hepatic arterial inflow using a fresh cadaveric iliac artery homograft. The patient was discharged home on postoperative day 8 in good clinical condition. After 60 months of follow-up, the patient is well and with a patent vascular homograft. The use of a fresh cadaveric iliac homograft described here may represent an option in young patients with low operative risk undergoing visceral artery aneurysm repair.

2011 - Understanding Tumor-Stroma Interplays for Targeted Therapies by Armed Mesenchymal Stromal Progenitors: The Mesenkillers. [Articolo su rivista]
Grisendi, Giulia; Bussolari, Rita; Veronesi, Elena; Piccinno, MARIA SERENA; Burns, J. S.; DE SANTIS, Giorgio; Loschi, Pietro; Pignatti, M.; DI BENEDETTO, Fabrizio; Ballarin, Roberto; C., Di Gregorio; V., Guarneri; Piccinini, Lino; Em, Horwitz; Paolucci, Paolo; P., Conte; Dominici, Massimo
abstract

Tumor represents a complex structure containing malignant cells strictly coupled with a large variety of surroundingcells constituting the tumor stroma (TS). In recent years, the importance of TS for cancer initiation, development,local invasion and metastases became increasingly clear allowing the identification of TS as one of the possibleways to indirectly target tumors. Inside the heterogeneous stromal cell population, tumor associated fibroblasts(TAF) play a crucial role providing both functional and supportive environments. During both tumor and stroma development,several findings suggest that TAF could be recruited from different sources such as locally derived host fibroblasts,via epithelial/endothelial mesenchymal transitions or from circulating pools of fibroblasts deriving form mesenchymalprogenitors, namely mesenchymal stem/stromal cells (MSC). These insights prompted scientists to identifymultimodal approaches to target TS by biomolecules, monoclonal antibodies and, more recently, via cell basedstrategies. These latter appear extremely promising, although associated with still debated and unclear findings. Thisreview discusses on crosstalk between cancers and their stroma, dissecting specific tumor types, such as sarcoma,pancreatic and breast carcinoma where stroma plays distinct paradigmatic roles. The recognition of these distinctstromal functions may help in planning effective and safer approaches aimed either to eradicate or to substitute TSby novel compounds and/or MSC having specific killing activities

2011 - University of Modena Experience in HIV-Positive Patients Undergoing Liver Transplantation. [Articolo su rivista]
DI BENEDETTO, Fabrizio; Tarantino, Giuseppe; N., De Ruvo; N., Cautero; R., Montalti; G. P., Guerrini; R., Ballarin; Spaggiari, Mario; Smerieri, Nazareno; Serra, Valentina; Rompianesi, Gianluca; G., D'Amico; A., Mimmo; R. M., Iemmolo; M., Codeluppi; Cocchi, Stefania; Guaraldi, Giovanni; Gerunda, Giorgio Enrico
abstract

IntroductionHighly effective antiretroviral therapy in the last decade has increased the survival rates of HIV-positive patients, yielding a greater number of HIV patients suffering from liver-related disease. Liver transplantation (LT) is the only curative treatment for end-stage liver disease (ESLD) associated or not with hepatocellular carcinoma (HCC).Patients and methodsFrom June 2003 to September 2010, 23 patients underwent cadaveric donor LT for ESLD at our institution. Inclusion criteria followed the Italian Protocol for LT in HIV-positive patients. Immunosuppressive regimens were based on cyclosporine or tacrolimus, eventually switched to Rapamycin.ResultsThe median CD4 T-cell count was 275/mmc (range = 119–924). All patients were affected by ESLD, which was associated with HCC in 14 cases. Ten patients were within the Milan criteria and four patients exceeded them but were within the San Francisco criteria. Conversion from calcineurin inhibitors (CNI) to rapamycin occurred in ten cases. Hepatitis C virus (HCV) recurrence occurred in 13/21 HCV-positive patients. Acute cellular rejection occurred in eight patients with one developing chronic cellular rejection. Overall patient and graft survivals at 80 months were 50% and 45% respectively.DiscussionLT in HIV-positive patients is a feasible procedure, even if in our experience was burdened by a greater incidence of complications including HCV recurrence and infection compared with HIV-negative patients.

2011 - Unusual Paraneoplastic Syndrome Accompanies Neuroendocrine Tumours of the Pancreas [Articolo su rivista]
Helga, Bertani; Alessandro, Messerotti; DI BENEDETTO, Fabrizio; Raffaele, Manta; Milena, Greco; Federica, Casoni; Luisa, Losi; Rita, Conigliaro
abstract

Neuroendocrine tumours comprise a small percentage of pancreatic neoplasia (10%) (1). Diagnosis of neuroendocrine tumours is difficult, especially if the tumours are small and nonfunctional. CT scans, MRI, and nuclear scans are sufficiently sensitive assessment tools for tumours with diameters of at least 2cm; otherwise, the sensitivity and specificity of these techniques is less than 50% (2). Myasthenia gravis (MG) is a heterogeneous neuromuscular junction disorder that is primarily caused when antibodies form against the acetylcholine receptors (Ab-AchR). MG can develop in conjunction with neoplasia, making MG a paraneoplastic disease. In those cases, MG is most commonly associated with thymomas and less frequently associated with extrathymic malignancies. The mechanism underlying this paraneoplastic syndrome has been hypothesized to involve an autoimmune response against the tumour cells (3). No published reports have linked malignant pancreatic diseases with MG. Here, we report the case of a young woman, negative for Ab-AchR, with a neuroendocrine tumour in the pancreatic head, who experienced a complete resolution of her MG-like syndrome after surgical enucleation of the tumour.

2011 - Which Is the Last Stage before Packing in Elective Liver Surgery? [Articolo su rivista]
DI BENEDETTO, Fabrizio; Giuseppe, Tarantino; Giuseppe, D’Amico; Roberto, Ballarin; Gerunda, Giorgio Enrico
abstract

Non disponibile

2010 - Brucellosis in a patient with end-stage liver disease undergoing liver transplantation: successful treatment with tigecycline. [Articolo su rivista]
Cocchi, Stefania; Bisi, Luca; M., Codeluppi; C., Venturelli; DI BENEDETTO, Fabrizio; Ballarin, Roberto; Gerunda, Giorgio Enrico; F., Rumpianesi; Esposito, Roberto; Guaraldi, Giovanni
abstract

No abstract available.

2010 - Does HIV-related cholangiopathy exist in the setting of liver transplantation? [Articolo su rivista]
Spaggiari, Mario; Ballarin, Roberto; DI BENEDETTO, Fabrizio; R., Montalti; N. d., Ruvo; Cautero, Nicola; G., Guerrini; Gerunda, Giorgio Enrico
abstract

Biliary tract complications after liver transplantation represent a source of morbidity and mortality. Performing an analysis to evaluate whether HIV infection and its related comorbidities, such as HIV-related cholangiopathy, could be an unknown risk factor for biliary stricture, we found that HIV-positivity could lead to greater susceptibility to biliary damage. The pathogenesis of the damage seems to involve the pretransplant immunological status and the number and type of posttransplant infections, although further studies are needed.

2010 - Early Withdrawal of Calcineurin Inhibitors and Everolimus Monotherapy in de novo Liver Transplant Recipients Preserves Renal Function [Articolo su rivista]
Masetti, Michele; Montalti, R.; Rompianesi, Gianluca; Codeluppi, M.; Gerring, R.; Romano, Antonio; Begliomini, Bruno; DI BENEDETTO, Fabrizio; Gerunda, Giorgio Enrico
abstract

We designed a randomized trial to assess whether the early withdrawal of cyclosporine (CsA) followed by the initiation of everolimus (Evr) monotherapy in de novo liver transplantation (LT) patients would result in superior renal function compared to a CsA-based im- munosuppression protocol. All patients were treated with CsA for the first 10 days and then randomized to receive Evr in combination with CsA up to day 30, then either continued on Evr monotherapy (Evr group) or maintained on CsA with/without mycophenolate mofetil (CsA group) in case of chronic kidney disease (CKD). Seventy-eight patients were randomized (Evr n = 52; CsA n = 26). The 1-year freedom from effi- cacy failure in Evr group was 75% versus 69.2% in CsA group, p = 0.36. There was no statistically significant difference in patient survival between the two groups. Mean modification of diet in renal disease (MDRD) was significantly better in the Evr group at 12 months (87.7 ± 26.1 vs. 59.9 ± 12.6 mL/min; p &lt; 0.001). The incidence of CKD stage ≥3 (estimated glomerular fil- tration rate &lt;60 mL/min) was higher in the CsA group at 1 year (52.2% vs. 15.4%, p = 0.005). The results in- dicate that early withdrawal of CsA followed by Evr monotherapy in de novo LT patients is associated with an improvement in renal function, with a similar inci- dence of rejection and major complications.

2010 - First report on a series of HIV patients undergoing rapamycin monotherapy after liver transplantation [Articolo su rivista]
Di Benedetto, F; Di Sandro, S; De Ruvo, N; Montalti, R; Ballarin, R; Guerrini, Gp; Spaggiari, M; Guaraldi, G; Gerunda, G
abstract

Some experimental trials have demonstrated that rapamycin (RAPA) is able to inhibit HIV-1 progression in three different ways: (1) reducing CCR5-gene transcription, (2) blocking interleukin-2 intracellular secondary messenger (mammalian target of rapamycin), and (3) up-regulating the beta-chemokine macrophage inflammatory protein (MIP; MIP-1alpha and MIP-1beta). We present the preliminary results of a prospective nonrandomized trial concerning the first HIV patient series receiving RAPA monotherapy after liver transplantation (LT).Since June 2003, 14 HIV patients have received cadaveric donor LT due to end-stage liver disease (ESLD) associated or not associated with hepatocellular carcinoma, scored by the model for ESLD system. Patients were assessed using the following criteria for HIV characterization: CD4 T-cell count more than 100/mL and HIV-RNA levels less than 50 copies/mL. Primary immunosuppression was based on calcineurin inhibitors (CI), whereas switch to RAPA monotherapy occurred in cases of CI complications or Kaposi's sarcoma.Mean overall post-LT follow-up was 14.8 months (range: 0.5-52.6). Six of 14 patients were administered RAPA monotherapy. Mean preswitch period from CI to RAPA was 67 days (range: 10-225 days). Mean postswitch follow-up was 11.9 months (range: 2-31 months). All patients were affected by ESLD, which was associated with hepatocellular carcinoma in seven patients. ESLD occurred due to hepatitis C virus (HCV)-related hepatopathy for nine patients, hepatitis B virus-related hepatopathy for one patient, and hepatitis B virus-HCV hepatopathy for four patients. Significantly better control of HIV and HCV replication was found among patients taking RAPA monotherapy (P=0.0001 and 0.03, respectively).After in vitro and in vivo experimental evidence of RAPA antiviral proprieties, to our knowledge, this is the first clinical report of several significant benefits in long-term immunosuppression maintenance and HIV-1 control among HIV positive patients who underwent LT.

2010 - HIV-positive patients with liver metastases from colorectal cancer deserve the same therapeutic approach as the general population. [Articolo su rivista]
M., Berretta; E., Zanet; F., Basile; A. L., Ridolfo; DI BENEDETTO, Fabrizio; A., Bearz; S., Berretta; G., Nasti; U., Tirelli
abstract

No abstract available.

2010 - [Is there an age limit for radical surgery in case of tumors infiltrating the duodenum?] [Articolo su rivista]
Ballarin, Roberto; Spaggiari, Mario; DI BENEDETTO, Fabrizio; N. D., Ruvo; Cautero, Nicola; R., Montalti; G. P., Guerrini; C., Longo; A., Mimmo; G., D'Amico; Gerunda, Giorgio Enrico
abstract

AIM: Radical resection is the only potential cure for pancreatic malignancies and a useful treatment for other benign diseases, such as pancreatitis. Over the last two decades, medical and surgical improvements have drastically changed the postoperative outcome of elderly patients undergoing pancreatic resection, and appropriate treatment for elderly potential candidates for pancreatic resection has become an important issue. METHODS: A hundred and five consecutive patients undergoing radical pancreatic resection between 2003 and 2007 at the Surgery Unit of the University of Modena, Italy, were considered and divided into two groups according to their age, i.e., over 75-year olds (group 1, 25 patients) and under 75-year-olds (group 2, 80 patients). The two groups were compared as regards to demographic features, American Society of Anesthesiologists scores, comorbidities, previous major surgery, surgical procedure, postoperative mortality, and morbidity. RESULTS: There were no significant differences between the two groups concerning postoperative mortality, and the duration of hospital stay and days in the postoperative Intensive Care Unit were also similar. Complications such as pancreatic fistulas, wound infections, and pneumonia were more frequent in the older group, but the differences were not statistically significant. CONCLUSION: In the light of these findings and as reported for other series, old age is probably not directly related with any increase in the rate of postoperative complications, but comorbidities (which are naturally related to the patients' previous life) may have a key role in the postoperative course.

2010 - Kabuki syndrome and cancer in two patients. [Articolo su rivista]
M., Tumino; M., Licciardello; G., Sorge; M. C., Cutrupi; DI BENEDETTO, Fabrizio; L., Amoroso; R., Catania; M., Pennisi; S., D'Amico; A. D., Cataldo
abstract

Both hepatoblastoma and neuroblastoma are occasionally associated with congenital syndromes such as Beckwith-Wiedemann syndrome and trisomy 18. There have been no reports of hepatoblastoma in patients with Kabuki syndrome, whereas one patient with neuroblastoma and this syndrome has been reported. In this paper we present two patients with Kabuki syndrome and a neoplasm: a child of 6 years with hepatoblastoma and an infant, of 6 months affected by neuroblastoma.

2010 - Liver or combined liver-kidney transplantation for autosomal dominant polycystic kidney disease [Abstract in Atti di Convegno]
D'Amico, G.; Di Benedetto, F.; Tarantino, G.; De Ruvo, N.; Cautero, N.; Montalti, R.; Guerrini, G. P.; Ballarin, R.; Spaggiari, M.; Baisi, B.; Cappelli, G.; Gerunda, G. E.
abstract

Autosomal dominant polycystic kidney disease ADPKD is a rare disorder, characterized by multiple macroscopic liver and kidney cysts. Isolated Liver transplantation or combined with kidney is a treatment option for these patients with regards to complications arising in hepatic and kidney cysts that are not controlled by other procedures

2010 - Liver transplantation due to iatrogenic injuries: two case reports. [Articolo su rivista]
DI BENEDETTO, Fabrizio; A., Mimmo; G., D'Amico; N. D., Ruvo; Cautero, Nicola; R., Montalti; G. P., Guerrini; Ballarin, Roberto; Spaggiari, Mario; G., Tarantino; V., Serra; Pecchi, Annarita; M. D., Santis; Gerunda, Giorgio Enrico
abstract

The transjugular intrahepatic portosystemic shunt (TIPS) is an acceptable procedure that has proven benefits in the treatment of patients who have complications from portal hypertension due to liver cirrhosis. In the literature few reports have described complications after TIPS placement. Initial surgery and local hemostasis have been needed to manage abdominal bleeding: if this treatment is insufficient, it may be necessary to perform a liver transplantation. This report describes the role of liver transplantation to manage dangerous complications in 2 patients after TIPS placement, when surgical procedures and hemostasis were unable to stop the bleeding.

2010 - Liver transplantation in patients aged 65 and over: a case-control study. [Articolo su rivista]
R., Montalti; G., Rompianesi; DI BENEDETTO, Fabrizio; R., Ballarin; R. C., Gerring; S., Busani; L. D., Pietri; N. D., Ruvo; R. M., Iemmolo; G. P., Guerrini; N., Smerieri; Gerunda, Giorgio Enrico
abstract

INTRODUCTION: The average age of patients undergoing liver transplantation (LT) is consistently increasing. The aim of this case-control study is to evaluate survival and outcome of patients ≥65 yr compared to younger patients undergoing LT. MATERIALS AND METHODS: From 10/00 to 4/08 we performed 330 primary LT, 31 (9.4\%) of these were in patients aged 65-70. Following a case-control approach, we compared these patients with 31 patients aged between 41 and 64 yr and matched according to sex, LT indication, viral status, cadaveric/living donor, LT timing, and Model for End-Stage Liver Disease (MELD) score. RESULTS: There were no statistically significant differences in demographic and surgical donor characteristics. The mean MELD score was under 18 in both groups. Post-LT complications occurred with a similar incidence in the two groups. one-, three-, and five-yr survival was 83.9\%, 80.6\%, and 80.6\%, respectively, for the elderly group, and 80.6\%, 73.8\%, and 73.8\%, respectively, for the young group (p = 0.61). DISCUSSION: Patients aged between 65 and 70 with low MELD score who undergo LT have the same short- and middle-term survival expectancy, morbidity, and outcome quality as younger patients with the same indication and same pre-LT pathology severity, whatever they might be. Thus, chronological age alone should not deter LT workup in patients >65 and <70.

2010 - Long term survival in a patient with adenocarcinoma of the cystic duct. [Articolo su rivista]
M., Berretta; Di Benedetto, Fabrizio; A., Lleshi; M., Ristagno; A., Cappellani; A., Bearz; S., Berretta; U., Tirelli
abstract

Not available

2010 - Longitudinal assessment of pre-transplant mortality risk among HIV-infected and uninfected patients with end-stage liver disease: the role of delta-meld score [Abstract in Rivista]
S., Cocchi; Zona, Stefano; R., Montalti; DI BENEDETTO, Fabrizio; M., Codeluppi; Gerunda, Giorgio Enrico; Esposito, Roberto; Guaraldi, Giovanni
abstract

The need for liver transplantation (LTx) has recently increased due to higher rates of end-stage liver disease (ESLD) associated with hepatitis C virus co-infection. Hence, LTx is now considered a definitive therapeutic option for selected HIV-positive patients. The model for ESLD (MELD) scoring system is the prevailing criterion for organ allocation, but its reliability has not been fully established in HIV-infected patients. Moreover, the change in MELDscore over time (Delta-MELD) may be a more accurate predictor of adverse outcomes in this population. The primary objective was to assess the role of Delta-MELD score as indipendent predictor of pre-transplant mortality in HIV-infected LTx candidates. The secondary objective was to determine factors associated with predictors of pre-transplant mortality in this population.

2010 - No age limit for liver transplant donors. [Articolo su rivista]
Ballarin, Roberto; Spaggiari, Mario; DI BENEDETTO, Fabrizio; R., Montalti; N. D., Ruvo; Cautero, Nicola; L., Losi; Bagni, Alessandra; A., D'Errico; Gerunda, Giorgio Enrico; G. E., Gerunda
abstract

No abstract available.

2010 - Novel genetic mutation in apolipoprotein E2 homozygosis and its implication in organ donation: a case report [Articolo su rivista]
Cautero, Nicola; DI BENEDETTO, Fabrizio; N., De Ruvo; R., Montalti; Guerrini, Gian Piero; Ballarin, Roberto; Spaggiari, Mario; Smerieri, Nazareno; DE BLASIIS, Maria Grazia; Rompianesi, Gianluca; R. M., Iemmolo; M., Marino; Bertolotti, Marco; S., Zivieri; Gerunda, Giorgio Enrico
abstract

Disorders in lipoprotein metabolism do not contraindicate liver procurement and transplantation (LT). In this circumstance, LT provides an intriguing opportunity to assess the in vivo contribution of the liver to the synthesis and degradation of genetically polymorphic plasma proteins. Apolipoprotein (APO) E exists with several common phenotypic differences due to gene polymorphism. Some authors have shown that the APOE phenotype of the recipient was virtually completely converted to that of the donor, providing evidence that >90\% of plasma APOE arises from the liver. Homozygosis for APOE2 (E2-E2) is related to an increased incidence of type III hyperlipoproteinemia (HLP). Recently, some authors have identified 4 new APOE mutations that are strongly linked to a unique entity of renal lipidosis called lipoprotein glomerulopathy (LPG). At present, 65 cases of LPG have been reported worldwide, although most patients have been discovered in Japan and other East Asian countries. We have herein reported a case of LT in a patient with advanced hepatocarcinoma who received a liver from a caucasian donor affected by type III HLP due to homozygous E2-E2. The LPG was due to a novel genetic mutation in APOE. After the LT, the recipient, developed de novo severe lipid abnormalities despite good graft function. To our knowledge this is the first report of an LT using a graft from a non Asian donor with homozygous E2-E2 with the presence of a novel APOE mutation.

2010 - Predictive factors of lack of response to antiviral therapy among in patients with recurrent hepatitis C after liver transplantation. [Articolo su rivista]
M., Marino; R. M., Iemmolo; R., Montalti; Bertolotti, Marco; DI BENEDETTO, Fabrizio; N. D., Ruvo; Cautero, Nicola; G., Guerrini; DE BLASIIS, Maria Grazia; Gerunda, Giorgio Enrico
abstract

The current therapy for hepatitis C recurrence after liver transplantation OLT is based on interferon (IFN) and ribavirin (RBV) in monotherapy or combination. The rate of sustained virological response (SVR) varies between 10% and 45%. We have retrospectively analyzed factors that could predict SVR after antiviral therapy. We analyzed 42 patients who completed a cycle of therapy with natural or pegylated IFN plus RBV. There were 15 (35.7%) patients who obtained an SVR. The following factors were significantly associated with a lack of SVR: donor age &gt;or=50 years (P = .046); donor body mass index (BMI) &gt; 27 (P = .016); genotype 1 versus 2 to 3 (P = 0.010), aspartate transferase (AST) before therapy &gt;or= 140 U/L (P = .046), alanine transferase before therapy &gt;or= 280 U/L (P = .055), use of natural IFN versus pegylated IFN (P = .016). The only factors remaining after multivariate analysis were: donor BMI, AST before therapy and genotype. Our data confirmed that genotype 1 was associated with poorer outcomes; other additional parameters can influence the response to antiviral therapy.

2010 - Pulmonary Hypertension as a Predictor of Postoperative Complications and Mortality After Liver Transplantation [Articolo su rivista]
L., De Pietri; R., Montalti; Begliomini, Bruno; A., Reggiani; L., Lancellotti; S., Giovannini; DI BENEDETTO, Fabrizio; G., Guerrini; V., Serra; G., Rompianesi; Pasetto, Alberto; Gerunda, Giorgio Enrico
abstract

Most transplant centers consider severe pulmonary hypertension (PHT) to be an absolute contraindication for orthotopic liver transplantation (OLT). We retrospec- tively examined the outcome of 24 patients with PHT (group 1) who underwent OLT compared with 24 matched patients (group 2) without PHT, who also underwent OLT. Based on right cardiac catheterization measurements made after the induction of anesthesia for OLT, PHT was defined as mild or moderate-to-severe if the mean pulmonary arterial pressure exceeded 25 or 35 mm Hg, respectively. The incidence of PHT was 9.8% (24/244); 21/24 PHT patients showed mild and 3/24 moderate PHT. Kaplan-Meier survival analysis did not show a significant difference between the two groups. The incidence of pulmonary infections was significantly greater in group 1 (P .05). The duration of ventilation and intensive care unit stay was similar in the two groups. Echocardiography detected only the three moderate cases of PHT and not the twenty-one cases of mild PHT. Our analysis suggested that mild PHT was common and did not affect patient outcomes after OLT; moderate or severe PHT was uncommon. The two patients with moderate PHT survived OLT and did not succum to PHT during long-term follow-up.

2010 - Rapamycin and HIV Replication in Liver Transplant Recipients [Articolo su rivista]
Di Benedetto, F.; Di Sandro, S.; Ballarin, R.; Guaraldi, G.; Gerunda, G.
abstract

not available

2010 - Role of magnetic resonance cholangiography in biliary complications of orthotopic liver transplantation. [Articolo su rivista]
Pecchi, Annarita; M. D., Santis; DI BENEDETTO, Fabrizio; Gibertini, Maria Chiara; Gerunda, Giorgio Enrico; Torricelli, Pietro
abstract

PURPOSE: The aim of this study was to evaluate the role of magnetic resonance cholangiography (MRC) in the detection of biliary complications following orthotopic liver transplantation (OLT). MATERIALS AND METHODS: Seventy-eight transplant patients with clinically suspected biliary complications were evaluated with 1.5-T magnetic resonance imaging (MRI) using a surface coil. All patients were imaged with the following sequences: axial T1-weighted and axial and coronal T2-weighted, 2D spin echo (SE) breath-hold radial cholangiography, and coronal 3D single-shot turbo spin echo (SS-TSE) with respiratory triggering. Patients with negative MRI underwent clinical and sonographic followup. When biliary complications were present, diagnostic confirmation was obtained by endoscopic retrograde cholangiopancreatography (ERCP) (n=13), percutaneous transhepatic cholangiography (PTC) (n=20), ultrasonography (n=10) or computed tomography (CT) (n=2). In 11 cases, surgical confirmation was also obtained. RESULTS: MRC detected biliary complications in 44/78 patients, in particular, 42 biliary strictures (37 anastomotic and five intrahepatic), 40 of which were confirmed by other imaging modalities. In 25/37 cases of anastomotic stricture, preanastomotic dilatation of the biliary tract was also demonstrated. Other MRC-detected biliary complications were biliary sludge (n=4), biloma (n=5), and biliary stones (n=3). In four cases, PTC revealed biliary complications that had not been detected with MRC (false negative results). In two cases, MRC showed unconfirmed strictures of the intrahepatic ducts and biliodigestive anastomosis (false positive results). The sensitivity, specificity, positive (PPV) and negative (NPV) predictive values and diagnostic accuracy of MRC were 93.5\%, 94.4\%, 96.7\%, 89.5\% and 93.9\%, respectively. CONCLUSIONS: Our results confirm that MRC is a reliable technique for depicting biliary anastomoses and detecting biliary complications after OLT. The high diagnostic accuracy of MRC indicates that this examination should be routinely employed in all OLT patients with clinically suspected biliary complications.

2010 - Thromboelastographic changes in liver and pancreatic cancer surgery: hypercoagulability, hypocoagulability or normocoagulability? [Articolo su rivista]
L. D., Pietri; R., Montalti; Begliomini, Bruno; Scaglioni, Giulia; G., Marconi; Reggiani, Alexia; DI BENEDETTO, Fabrizio; S., Aiello; Pasetto, Alberto; G., Rompianesi; Gerunda, Giorgio Enrico
abstract

BACKGROUND AND OBJECTIVE: Despite clinical and laboratory evidence of perioperative hypercoagulability, alterations in haemostasis after potentially haemorrhagic oncologic surgery are difficult to predict. This study aims to evaluate the entity, the extent and the duration of perioperative coagulative alterations following pancreas and liver oncologic surgery, by the use of both routine tests and thromboelastogram (TEG). METHODS: Fifty-six patients undergoing liver (n = 38) and pancreatic (n = 18) surgery were studied. The coagulation profile was evaluated by platelet count, prothrombin time-international normalized ratio, activated partial thromboplastin time, antithrombin III and TEG at the beginning, at the end of the operation and on postoperative days 1, 3, 5 and 10. RESULTS: All preoperative coagulative screening and TEG traces were normal before incision. In the postoperative period of the liver and pancreas groups, despite an increase in prothrombin time-international normalized ratio, a reduction in antithrombin III and platelet count and normal activated partial thromboplastin time and fibrinogen, TEG evidenced a normocoagulability in the liver group, with a major tendency towards hypocoagulability in the pancreas group, as evidenced by a transient increase in R-time and K-time between postoperative days 1 and 3. During the study period, four cases of pulmonary embolism, resolved with heparin infusion, were recorded, in the absence of laboratory and thromboelastographic evidence of hypercoagulability. CONCLUSION: Despite laboratory tests evidencing hypocoagulability in both groups, TEG traces showed a normocoagulability in liver resections, whereas a transient thromboelastographic hypocoagulability was evident in patients undergoing pancreas surgery. The discrepancy between laboratory values and thromboelastographic variables was even more evident in patients undergoing major liver resections compared with minor ones. Our study supports the role of thromboelastography, despite its limitations, as a valuable tool for the evaluation of the perioperative whole coagulation process and hypercoagulability changes and to increase patient safety through better management of antithrombotic therapy.

2010 - Two-stage liver transplantation: an effective procedure in urgent conditions. [Articolo su rivista]
Montalti, R.; Busani, S.; Masetti, M.; Girardis, Massimo; Benedetto, F. D.; Begliomini, B.; Rompianesi, G.; Rinaldi, L.; Ballarin, R.; Pasetto, A.; Gerunda, Giorgio Enrico
abstract

Temporary portocaval shunt and total hepatectomy is a technique used in the presence of toxic liver syndrome because of fulminant hepatic failure, hepatic trauma, primary non-function (PNF), and eclampsia. We performed this technique on four patients. An indication for anhepatic state was severe hemodynamic instability in three of them. Etiologies of these three patients were as follows: PNF after liver transplantation, ischemic hepatitis after right hepatic artery embolization, and massive reperfusion syndrome during a liver transplantation. In the fourth patient, during the liver transplantation when hepatic artery was ligated, a kidney carcinoma in the donor graft was discovered. We decided to complete the hepatectomy and to construct a temporary portocaval shunt. Mean anhepatic phases were 19 h and 15 min. All patients survived the two-stage liver transplantation procedure without major complications. Our cases demonstrated that temporary portocaval shunt while awaiting urgent liver transplantation could be an effective "bridge" in selected patients who develop toxic liver syndrome; however, a short time between portocaval shunt and transplantation and careful intensive care managements are mandatory.

2010 - Univariate and multivariate analysis of prognostic factors in the surgical treatment of hilar cholangiocarcinoma. [Articolo su rivista]
G., Ramacciato; G., Nigri; R., Bellagamba; N., Petrucciani; M., Ravaioli; M., Cescon; M. D., Gaudio; G., Ercolani; DI BENEDETTO, Fabrizio; N., Cautero; C., Quintini; A., Cucchetti; A., Lauro; C., Miller; A. D., Pinna
abstract

Surgery is the only effective treatment able to improve survival of patients with hilar cholangiocarcinoma (CCA). However, the significance of prognostic factors on overall survival is still debated. We evaluated early and long-term outcomes of patients resected for hilar cholangiocarcinoma over a 3-year period to determine the role of prognostic factors and their effect on overall survival. Medical records of patients with hilar CCA who underwent resection between January 2001 and December 2004 were retrospectively reviewed. Univariate and multivariate analysis was performed to identify prognostic factors associated with survival. Thirty-two of 45 patients underwent surgical resection with curative intent. Morbidity was 24.4 per cent; perioperative mortality was 0 per cent. Overall median survival was 22.3 months. Well-differentiated tumor grading and R0 resection were independently associated with better survival at multivariate analysis. Aggressive surgery, including biliary resection combined with major hepatectomy, is a safe procedure with low morbidity and mortality in a tertiary referral hepatobiliary center. The main aim of an aggressive surgical approach is to obtain a microscopic margin-negative resection, which is associated with better prognosis. Another important prognostic factor is tumor grading, which is independently associated with survival.

2009 - Clinical presentation and outcome of colorectal cancer in HIV-positive patients: A clinical case-control study [Articolo su rivista]
M., Berretta; A., Cappellani; DI BENEDETTO, Fabrizio; A., Lleshi; R., Talamini; V., Canzonieri; E., Zanet; A., Bearz; G., Nasti; T., Lacchin; S., Berretta; R., Fisichella; L., Balestreri; A., Torresin; I., Izzi; P., Ortolani; U., Tirelli
abstract

Data on colorectal cancer (CRC) in HIV-positive patients are limited. The study objective was to investigate and compare clinical presentation and outcome between HIV-positive and HIV-negative CRC patients.Between September 1985 and November 2003 we identified 27 cases of HIV-positive CRC patients from the cancer registry database - Italian Cooperative Group AIDS and Tumours (GICAT); the clinical presentation/outcome information was retrieved. Each HIV-positive patient from our institution was randomly matched (ratio 1:2) with HIV-negative patients (54 controls) based on age, sex, and year of diagnosis in the same time period. Differences in clinical presentation, treatment, and overall survival were assessed.Of 1130 HIV-negative CRC patients, 54 were identified and matched with 27 HIV-positive patients. Compared with the HIV-negative patients, the HIV-positive patients had a higher risk of lower performance status (PS: > or =2) (odds ratio (OR) = 14.4; 95\% confidence interval (CI): 3.6-57.7), a higher risk of unfavorable Dukes' stage (D) (OR = 4.9; 95\% CI: 1.8-13.5), and a higher risk of poor grading (G3-G4) (OR = 5.0; 95\% CI: 1.9-13.4). Median overall follow-up was 27 months (range: 2-212). At multivariate analysis, the only characteristics that significantly reduced the survival of the CRC patients were: HIV-positive status (hazard ratio (HR): 2.4; 95\% CI: 1.1-5.2) and Dukes' stage D (HR: 3.7; 95\% CI: 1.9-7.1).Our data show that HIV-positive CRC patients compared to HIV-negative patients have a poorer PS, an unfavorable Dukes' stage, higher grading and shorter survival.

2009 - Cystic pancreatic neuroendocrine neoplasms with uncertain malignant potential: Report of two cases [Articolo su rivista]
Ballarin, R; Masetti, M; Losi, L; Di Benedetto, F; Di Sandro, S; De Ruvo, N; Montalti, R; Romano, A; Guerrini, Gp; DE BLASIIS, Maria Grazia; Spaggiari, M; Gerunda, Ge.
abstract

Neuroendocrine tumors of the pancreas (NETP) represent only 1%-2% of all pancreatic neoplasms. They can be classified as functioning or non-functioning, respectively, according to the presence or absence of paraneoplastic syndrome. Case 1 concerned a 70-year-old woman with a cystic lesion of the pancreatic head and body. All tumor markers were negative. The patient underwent a distal pancreatectomy. The histology revealed a well-differentiated endocrine tumor with uncertain malignant potential. Case 2 was a 61-year-old man with chronic polyserositis. The serum tumor markers were negative, while he was strongly positive for intracystic tumor markers carcinoembryonic antigen, carbohydrate antigen (CA) 19-9, and CA 125. The patient underwent a cephalo-pancreatic duodenectomy. The preoperative differential diagnosis of cystic NETP is still a challenge due to the high rate of the nonfunctional variant. Although cystic NETPs are well differentiated, they are still tumors with a malignant potential, and therefore an early diagnosis and radical surgical resection could be associated with a better long-term survival.

2009 - Differential Dose Adjustments of Immunosuppressants after Resuming Boosted versus Unboosted HIV-Protease Inhibitors Postliver Transplant. [Articolo su rivista]
Guaraldi, Giovanni; Cocchi, S.; Motta, A.; Ciaffi, S.; Conti, C.; Codeluppi, M.; Bonora, S.; Zona, S.; DI BENEDETTO, Fabrizio; Pinetti, Diego; D'Avolio, A.; Bertolini, A.; Esposito, Roberto
abstract

Pharmacokinetic (PK) interactions between protease inhibitors (PI(s)) and immunosuppressive agents (IS) are critical elements in the management of HIV-infected patients who undergo liver transplantation (LT(x)). The primary objective of this study was to evaluate the decreases in IS dosages necessary to maintain an appropriate therapeutic window (TW) after initiating PI-based antiretroviral therapy regimens post-LT(x). Single-center, PK cross-sectional study of consecutive HIV-infected adult patients who underwent LT(x) was done. Blood trough concentrations (C(t)) of IS were obtained using a commercial MEIA test; plasma C(t) of PI(s) were measured using HPLC. Twelve consecutive HIV-infected adult patients (11 males, 1 female) were enrolled. More rapid increases in IS plasma C(t) were observed 48 h after initiating ritonavir (RTV)-boosted PI therapy post-LT(x) than when using unboosted PI(s). Seven patients developed acute renal failure. The median fold decrease in IS dosages required to regain IS concentrations that were in the TW was 7.5 (range 6-14) after resuming boosted PI(s) and 2.9 (range 2-4) after unboosted PI(s). The overall median time necessary to reach IS TW after dose adjustment was 3.5 days (range 0-15). Unboosted PI(s) exhibited lesser PK interactions with IS than did RTV-boosted PI(s) and were thus more amenable to use in the post-LT(x) setting.

2009 - Do not deny pancreatic resection to ederly patients [Articolo su rivista]
Allarin, R; Spaggiari, Mario; DI BENEDETTO, Fabrizio; Montalti, R; Masetti, R; Deruvo, N; Romano, Antonio; Guerrini, Gian Piero; Deblasiis, Mg; Gerunda, Giorgio Enrico
abstract

INTRODUCTION: Radical resection is the only potential cure for pancreatic malignancies and a useful treatment for other benign diseases, such as pancreatitis. Over the last two decades, medical and surgical improvements have drastically changed the postoperative outcome of elderly patients undergoing pancreatic resection, and appropriate treatment for elderly potential candidates for pancreatic resection has become an important issue. MATERIALS AND METHODS: Ninety-eight consecutive patients undergoing radical pancreatic resection between 2003 and 2006 at the Surgery Unit of the University of Modena, Italy, were considered and divided into two age groups, i.e., over 75-year-olds (group 1, 23 patients) and under 75-year-olds (group 2, 75 patients). The two groups were compared as regards demographic features, American Society of Anesthesiologists scores, comorbidities, previous major surgery, surgical procedure, postoperative mortality, and morbidity. RESULTS: There were no significant differences between the two groups concerning postoperative mortality, and the duration of hospital stay and days in the postoperative intensive care unit were also similar. Complications such as pancreatic fistulas, wound infections, and pneumonia were more frequent in the older group, but the differences were not statistically significant. The overall median survival was 29.4 months and did not differ significantly between the two groups when calculated using the log-rank test (p = 0.961). DISCUSSION: In the light of these findings and as reported for other series, old age is probably not directly related with any increase in the rate of postoperative complications, but comorbidities (which are naturally related to the patients' previous life) may have a key role in the postoperative course.

2009 - Efficacy and safety of atazanavir in patients with end-stage liver disease. [Articolo su rivista]
Guaraldi, Giovanni; S., Cocchi; A., Motta; S., Ciaffi; M., Codeluppi; S., Bonora; DI BENEDETTO, Fabrizio; Masetti, Michele; M., Floridia; S., Baroncelli; D., Pinetti; A., Bertolini; Gerunda, Giorgio Enrico; Esposito, Roberto
abstract

BACKGROUND: No data are available on the use of atazanavir (ATV) in patients with end-stage liver disease (ESLD), and guidelines discourage its use in this setting. The objective of our study was to evaluate the efficacy and safety of unboosted ATV in patients infected with HIV and suffering from ESLD who had been screened for orthotopic liver transplantation (OLT(x)). PATIENTS AND METHODS: This was a single-arm, 24-week pilot study. Atazanavir-naïve patients undergoing a highly active antiretroviral therapy were switched to ATV 400 mg daily plus two non-thymidine nucleoside reverse transcriptase inhibitors. RESULTS: Fifteen patients (ten males and five females, age range 36-59 years) were enrolled in the study. Of these, 11 (73%) had a baseline CD4 cell count > 200 microl(-1), and 12 had undetectable plasma HIV-RNA. 12 subjects (80%) were able to remain on ATV until week 24 (n = 10) or transplantation (n = 2). At the end of the study, the median CD4 cell count was 340 microl(-1) , and nine of the ten patients had undetectable RNA. During the study period, two patients received a transplant, two died of intracerebral hemorrhage and lactic acidosis, respectively, and one discontinued ATV. Among the ten patients completing the 24-week study, no significant changes from baseline were observed for most of the liver function markers, with the exception of unconjugated bilirubin (from 1.15 mg/dl to 1.32 mg/dl, p = 0.047). CONCLUSIONS: Unboosted ATV treatment did not worsen liver disease and was able to maintain or gain immunovirological eligibility for OLT(x) in all patients, with a limited effect on unconjugated bilirubin. These results suggest that ATV is an easy-to-use drug in patients with ESLD.

2009 - Immunosuppressive Switch to Sirolimus in Renal Dysfunction After Liver Transplantation [Articolo su rivista]
DI BENEDETTO, Fabrizio; Di Sandro, S; De Ruvo, N; Montalti, R; Guerrini, Gp; Ballarin, R; Spaggiari, Mario; Mimmo, A; D'Amico, G; Cautero, N; Iemmolo, Rm; Gerunda Giorgio, Enrico.
abstract

OBJECTIVE: Nephrotoxicity is a serious adverse effect after liver transplantation often related to calcineurin inhibitors (CNI) with a incidence of 18.1% at 5 years. Sirolimus (SRL) is a new immunosuppressive drug that was introduced into solid organ transplant management in 1999. Herein we have performed a retrospective review of patients who developed renal insufficiency owing to CNI therapy after orthotopic liver transplantation (OLT). MATERIALS AND METHODS: Thirty-one patients were switched to SRL monotherapy because of nephrotoxicity as evidenced by serum creatinine levels (SCr) &gt; 1.8 mg/dL and estimated glomerular filtration rates (eGFR) &lt; 45 mL/min/1.73 m(2). The dosage was adjusted to achieve trough levels between 8 and 10 ng/mL. RESULTS: The patients were followed for a mean of 52 months (range 2-88 months) after OLT. Mean follow-up after the switch was 27.5 months (range, 2-71.2 months). Immunosuppression was switched after a mean of 35.2 months (range, 0.2-43.4 months). Renal function was significantly improved, as shown by the improved SCr, urea, and eGFR after the switch. CONCLUSIONS: CNIs may be associated with significant nephrotoxicity and chronic kidney damage. Patients who develop renal dysfunction after OLT may be successfully treated by an early switch from CNIs to SRL, stopping the progression toward chronic renal damage and preserving allograft survival.

2009 - Liver transplantation utilizing grafts from donors with genitourinary cancer detected prior to liver implantation. [Articolo su rivista]
R., Montalti; Rompianesi, Gianluca; DI BENEDETTO, Fabrizio; Masetti, Michele; N. D., Ruvo; Ballarin, Roberto; Guerrini, Gian Piero; Smerieri, Nazareno; R. M., Iemmolo; L. D., Pietri; Gerunda, Giorgio Enrico
abstract

Expansion of the donor pool has led to reconsideration of selection criteria to obtain the largest number of grafts without compromising recipient outcomes. This reconsideration concerns the utilization of donors with malignancies. Herein we have analyzed the outcomes, survivals, and risks of cancer transmission among patients who received a liver transplant from a donor with a genitourinary malignancy. Six of 363 patients (1.5\%) who underwent transplantation at our center received an organ from a donor with a genitourinary cancer which was detected prior to the surgical harvest. Donors affected by low-grade renal cell carcinoma (Fuhrman grade 1 or 2) or low-grade intraprostatic prostate carcinoma (Gleason score <or= 6) were classified as "standard risk" and utilized pending informed consent. Four of 6 patients (66.6\%) succumbed, but none consequent to a neoplastic disease. The mean follow-up was 12 +/- 8.1 months; in no patient was there evidence of transmission of a donor malignancy. Despite a relatively high risk of liver metastases among patients with genitourinary neoplasms, the risk of tumor transmission to a liver recipient is low. It seems to be safe to utilize these donors for patients with a high risk of succumbing on the waiting list.

2009 - Pancreatic resections for malignancy in patients aged 70 and older. [Articolo su rivista]
DI BENEDETTO, Fabrizio; Ballarin, Roberto; N. D., Ruvo; M., Berretta; Spaggiari, Mario; R., Montalti; G. P., Guerrini; Gerunda, Giorgio Enrico
abstract

No abstract available.

2009 - Prevalence of Human Herpesvirus-6 Chromosomal Integration (CIHHV-6) in Italian Solid Organ and Allogeneic Stem Cell Transplant Patients [Articolo su rivista]
Potenza, Leonardo; Barozzi, Patrizia; Masetti, M; Pecorari, M; Bresciani, P; Gautheret Dejean, A; Riva, Giovanni; Vallerini, Daniela; Tagliazucchi, S; Codeluppi, M; DI BENEDETTO, Fabrizio; Gerunda, Giorgio Enrico; Narni, Franco; Torelli, Giuseppe; Luppi, Mario
abstract

The unique phenomenon of human herpesvirus-6 (HHV-6) chromosomal integration (CIHHV-6) may account for clinical drawbacks in transplant setting, being misinterpreted as active infection and leading to unnecessary and potentially harmful treatments. We have investigated the prevalence of CIHHV-6 in 205 consecutive solid organ (SO) and allogeneic stem cell transplant (alloSCT) Italian patients. Fifty-two (38.5%) of 135 solid organ transplant (SOT) and 16 (22.8%) of 70 alloSCT patients resulted positive for plasma HHV-6 DNA by real-time polymerase chain reaction. Seven SOT and three alloSCT patients presented HHV-6-related diseases, requiring antivirals. Two further patients (0.9%) were identified, presenting high HHV-6 loads. The quantification of HHV-6 on hair follicles disclosed the integrated state, allowing the discontinuation of antivirals. Before starting specific treatments, CIHHV-6 should be excluded in transplant patients with HHV-6 viremia by the comparison of HHV-6 loads on different fluids and tissues. Pretransplantation screening of donors and recipients may further prevent the misdiagnosis of CIHHV-6.

2009 - Sirolimus monotherapy effectiveness in liver transplant recipients with renal dysfunction due to calcineurin inhibitors [Articolo su rivista]
Di Benedetto, F; Di Sandro, S; De Ruvo, N; Spaggiari, M; Montalti, R; Ballarin, R; Cappelli, G; Gerunda, Ge.
abstract

INTRODUCTION: Among the adverse effects of different calcineurin inhibitors (CIs), nephrotoxicity is the most common (incidence: 18.1% at 13 y from liver transplantation) and depends on a variable degree of tubular-interstitial injury accompanied by focal glomerular sclerosis. A new immunosuppressive drug was introduced in solid organ transplant management, Sirolimus (SRL). It is a nonnephrotoxic immunosuppressor. METHODS: Twenty-six patients who developed nephrotoxicity owing to CIs, showing an increment of serum creatinine levels (&gt;1.8 mg/dL) were switched to SRL monotherapy, initially at a dosage between 3 and 5 mg/d, and subsequently adapted to achieve trough level between 8 to 10 ng/mL. RESULTS: Patients were followed-up for a mean period of 40.3 months (range, 8.4 to 76.7) from liver transplantation. Mean follow-up after switch was 27.5 months (range, 2 to 71.2). Immunosuppression therapy was converted after a mean period of 12.8 months (range, 0.2 to 43.4). Serum creatinine, urea, and estimated glomerular filtration rate were significantly improved. DISCUSSION: Patients developing renal dysfunction after liver transplantation may be successfully treated by conversion from CI to SRL. Hypertriglyceridemia and hypercholesterolemia represent the principal side effects from SRL, but are treatable. Furthermore, SRL can significantly improve glucose tolerance.

2009 - The impact of inherited thrombophilia on liver transplantation. [Articolo su rivista]
Spaggiari, Mario; DI BENEDETTO, Fabrizio; Masetti, Michele; Ballarin, Roberto; Romano, Antonio; Pietrangelo, Antonello; Gerunda, Giorgio Enrico
abstract

No abstract available

2009 - Thrombosis of developmental venous anomalies of the brain after liver transplantation. [Articolo su rivista]
Ballarin, Roberto; DI BENEDETTO, Fabrizio; N. D., Ruvo; Masetti, Michele; R., Montalti; Spaggiari, Mario; C., Longo; Gerunda, Giorgio Enrico
abstract

Developmental venous anomalies(DVAs), formerly known as venous angiomas,are nonpathologic changes invenous drainage from areas of cerebralwhite matter and are not true vascularmalformations (1). Most DVAs are clinicallysilent and are usually discoveredincidentally on enhanced computed tomographyor magnetic resonance imaging(MRI) of the brain.We report a case of 48-year-oldwoman who underwent liver transplantationfor HCV-related liver cirrhosis;pretransplant she had a Model forEnd-Stage Liver Disease score of 23, aChild-Pugh B9 and a United Networkfor Organ Sharing registry 2A.

2009 - Usutu virus infection in a patient who underwent orthotropic liver transplantation, Italy, August-September 2009. [Articolo su rivista]
Cavrini, F; Gaibani, P; Longo, Fulvio Giovanni; Pierro, Am; Rossini, Gian Paolo; Bonilauri, P; Gerunda, Giorgio Enrico; DI BENEDETTO, Fabrizio; Pasetto, Alberto; Girardis, Massimo; Dottori, M; Landini, Mp; Sambri, V.
abstract

We report a case of Usutu virus (USUV)-related illness in a patient that underwent an orthotropic liver transplant (OLT). Post transplant, the patient developed clinical signs of a possible neuroinvasive disease with a significant loss of cerebral functions. USUV was isolated in Vero E6 cells from a plasma sample obtained immediately before the surgery, and USUV RNA was demonstrated by RT-PCR and sequencing. This report enlarges the panel of emerging mosquito-borne flavivirus-related disease in humans.

2008 - A new endoscopic treatment for pancreatic fistula after distal pancreatectomy: a case report and review of literature. [Articolo su rivista]
Romano, Antonio; Spaggiari, Mario; Masetti, Michele; Sassatelli, R; DI BENEDETTO, Fabrizio; Deruvo, N; Montalti, R; Guerrini, Gian Piero; Ballarin, Roberto; Deblasiis, Mg; Gerunda, Giorgio Enrico
abstract

After the first distal pancreatectomies were performed by Billroth in 18841 and by Finney1 and Mayo,2 the high incidence of perioperative morbidity and death suggested that this procedure should be abandoned.3 Nevertheless, over the last few decades, surgical and medical improvements allowed a progressive decrease in morbidity and mortality rates linked to distal pancreatectomy, as described by Fernandez del Castillo et al4 in 1990.

2008 - A pilot study on the efficacy, pharmacokinetics and safety of atazanavir in patients with end-stage liver disease. [Articolo su rivista]
Guaraldi, Giovanni; Cocchi, Stefania; A., Motta; S., Ciaffi; M., Codeluppi; S., Bonora; DI BENEDETTO, Fabrizio; M., Masetti; M., Floridia; S., Baroncelli; D., Pinetti; A., D'Avolio; A., Bertolini; Esposito, Roberto
abstract

OBJECTIVES: Antiretroviral combinations including atazanavir are currently not recommended in HIV-infected patients with end-stage liver disease (ESLD). The objective of our study was to evaluate efficacy, pharmacokinetics and safety of unboosted atazanavir in HIV-infected patients with ESLD screened for orthotopic liver transplantation (OLT(x)). Patients and methods Single-arm, 24 week pilot study. Atazanavir-naive patients undergoing highly active antiretroviral therapy were switched to atazanavir 400 mg/day plus two non-thymidine nucleoside reverse transcriptase inhibitors. Results Fifteen patients (10 males and 5 females) were included. In the study period, 2 patients were transplanted and 10 completed 24 weeks of atazanavir treatment. Median area under the concentration-time curve at week 4 was 19 211 ng.h/mL (IQR = 8959-27 500). At week 24, median atazanavir trough concentrations (C(trough)) per patient calculated across the study were above the minimum effective concentration (MEC = 100 ng/mL) in 8 of 10 subjects. Atazanavir C(trough) time-point values were always above the MEC in five patients. The other three subjects experienced only one determination below the MEC, with median atazanavir C(trough) levels across the study being above the MEC in two of them. At 8 of 11 time-points when atazanavir and proton pump inhibitors (PPIs) were co-administered and at 16 of 19 time-points in which patients had a concomitant tenofovir association, atazanavir C(trough) was above the MEC. Conclusions Unboosted atazanavir showed a favourable pharmacokinetic profile and was able to maintain or gain immuno-virological eligibility for OLT(x) in all patients. Limited biochemical toxicities (including unconjugated hyperbilirubinaemia) and allowance of concomitant administration of tenofovir and PPIs were observed.

2008 - Adenocarcinoid tumor of the extrahepatic biliary tract. [Articolo su rivista]
Costantini, Matteo; Montalti, R; Losi, Lorena; Masetti, Michele; DI BENEDETTO, Fabrizio; Gerunda, Giorgio Enrico
abstract

The term adenocarcinoid was first coined by Warkel et al in 1978 to describe a group of uncommon low-grade malignant appendiceal tumors with morphologic and histochemical evidence of both glandular (adenocarcinoma) and neuroendocrine (carcinoid) differentiation for which several terms have been used in the past. Although the appendix is the most frequent site of this tumor, similar neoplasms have been reported also in other sites, such as colon, gallbladder, Vater's ampulla, and stomach. The biologic and clinical behavior of adenocarcinoid is still unclear. Provided that it can metastasize, a recent meta-analysis on appendiceal adenocarcinoids showed that right hemicolectomy is not required when the tumor is completely excised and there is no cecal involvement. In this article, the clinicopathologic features of an adenocarcinoid tumor occurring in the extrahepatic biliary tract with infiltration of the common hepatic duct wall that, to the best of our knowledge, represents the first report in this site is described.

2008 - Combined liver-kidney transplantation in an HIV-HCV-coinfected patient with haemophilia. [Articolo su rivista]
Ballarin, Roberto; DI BENEDETTO, Fabrizio; M., Masetti; Spaggiari, Mario; N. D., Ruvo; R., Montalti; A., Romano; Cocchi, Stefania; Guaraldi, Giovanni; Gerunda, Giorgio Enrico
abstract

No abstract available

2008 - FOLFOX-4 regimen with concomitant highly active antiretroviral therapy in metastatic colorectal cancer HIV-infected patients: a report of five cases and review of the literature. [Articolo su rivista]
M., Berretta; DI BENEDETTO, Fabrizio; A., Bearz; C., Simonelli; F., Martellotta; C. D., Ben; S., Berretta; M., Spina; U., Tirelli
abstract

Colorectal cancers are rare in developing countries, but are the second most frequent malignancy in the affluent world. Data on colorectal cancer in HIV-positive patients are limited. Up to now, there are no published data on treatment patterns, response to therapy, or survival in this setting. Oxaliplatin is an antineoplastic agent currently indicated, concomitantly to fluorouracil and leucovorin, for the treatment of advanced colorectal cancer. The FOLFOX-4 regimen (oxaliplatin 85 mg/m(2) as a two-hour infusion on day 1; leucovorin 200 mg/m(2) as a two-hour infusion on days 1 and 2, fluorouracil as a bolus infusion on days 1 and 2, followed by a fluorouracil 22-hour infusion 600 mg/m(2) for two consecutive days every two weeks), with concomitant highly active antiretroviral therapy (HAART) is feasible and active, while the HIV infection is not a limiting factor for its use. Moreover, the concomitant use of HAART does not seem to increase the toxicity of the FOLFOX-4 regimen.

2008 - Hepatocellular carcinoma in HIV patients treated by liver transplantation. [Articolo su rivista]
Di Benedetto, F.; De Ruvo, N.; Berretta, M.; Masetti, M.; Montalti, R.; Di Sandro, S.; Ballarin, R.; Codeluppi, M.; Guaraldi, G.; Gerunda, GE.
abstract

Several reports have shown the effectiveness of liver transplantation (LT) as a therapeutic option in HIV-patients affected by end-stage liver disease. HCC on cirrhosis is another major indication for LT. However, no reports, to our knowledge, have been published as yet addressing the important questions of indications and outcome of LT in HIV-patients with HCC, mainly because of concerns regarding a more aggressive course of HCC with respect to HCC seen in HIV-negative individuals. METHODS: The aim of this report is to focus on indications, preliminary results and complications of LT in a group of 7 HIV-patients who underwent LT at our department for HCC on cirrhosis. RESULTS: Indications to listing HIV-patients were HCC using the internationally accepted Milan criteria. All patients were HBV-and/or HCV-infected. The mean CD4+ cell-count was 249 (range 144-353), and the HIV-RNA load was undetectable in all but one case. After a mean follow-up period of 232days (range 33-774), no recurrence of HCC was seen; one patient died. CONCLUSION: Characteristics of the study protocol, the patients, virological and immunological features, tumor stage and pre-transplantation treatment, complications and survival are herein described in an effort to provide new insights into methodology for an aggressive management of HCC in HIV patients, and possibly give a greater chance of cure.

2008 - HHV-6A in syncytial giant-cell hepatitis [Articolo su rivista]
Potenza, Leonardo; Luppi, Mario; Barozzi, Patrizia; Rossi, Giulio; Cocchi, Stefania; Codeluppi, Mauro; Pecorari, Monica; Masetti, Michele; DI BENEDETTO, Fabrizio; Gennari, William; Portolani, Marinella; Gerunda, Giorgio Enrico; Lazzarotto, Tiziana; Landini, Maria Paola; Schulz, Thomas F.; Torelli, Giuseppe; Guaraldi, Giovanni
abstract

Syncytial giant-cell hepatitis is a rare but severe form of hepatitis that is associated with autoimmune diseases, drug reactions, and viral infections. We used serologic, molecular, and immunohistochemical methods to search for an infectious cause in a case of syncytial giant-cell hepatitis that developed in a liver-transplant recipient who had latent infection with variant B of human herpesvirus 6 (HHV-6B) and who had received the organ from a donor with variant A latent infection (HHV-6A). At the onset of the disease, the detection of HHV-6A (but not HHV-6B) DNA in plasma, in affected liver tissue, and in single micromanipulated syncytial giant cells with the use of two different polymerase-chain-reaction (PCR) assays indicated the presence of active HHV-6A infection in the patient. Expression of the HHV-6A-specific early protein, p41/38, but not of the HHV-6B-specific late protein, p101, was demonstrated only in liver syncytial giant cells in the absence of other infectious pathogens. The same markers of HHV-6A active infection were documented in serial follow-up samples from the patient and disappeared only at the resolution of syncytial giant-cell hepatitis. Neither HHV-6B DNA nor late protein was identified in the same follow-up samples from the patient. Thus, HHV-6A may be a cause of syncytial giant-cell hepatitis.

2008 - Human Immunodeficiency Virus and Liver Transplantation: Our Point of View [Articolo su rivista]
Di Benedetto, F.; Di Sandro, S.; De Ruvo, N.; Berretta, M.; Montalti, R.; Guerrini, G. P.; Ballarin, Roberto; De Blasiis, M. G.; Spaggiari, M.; Smerieri, Nazareno; Iemmolo, R. M.; Guaraldi, G.; Gerunda, G. E.
abstract

INTRODUCTION: Highly active antiretroviral therapy (HAART) has been able to improve the immune system function and survival of HIV patients with a consequent increase in the number of HIV patients affected by end-stage liver disease (ESLD). Between June 2003 and October 2006, 10 HIV-positive patients underwent liver transplantations in our center. METHODS: All patients were treated with HAART before transplantation; treatment was interrupted on transplantation day and was restarted once the patients' conditions stabilized. Five patients were hepatitis C virus (HCV)-positive, 3 were hepatitis B virus (HBV)-positive, and 2 were HBV-HCV coinfected. HIV viral load before transplantation was &lt;50 copies/mL in all cases. CD4+ cell count before transplantation ranged between 144 and 530 c/microL. Immunosuppression was based on Cyclosporine (CyA) and steroid weaning for 8 patients, and on Tacrolimus and steroid weaning for 2 patients. RESULTS: Five patients were cytomegalovirus (CMV)-positive pp65 antigenemia posttransplantation, and 1 patient was EBV-positive; 2 patients had a coinfection with HHV6. Four patients suffered from a cholestatic HCV recurrent hepatitis treated with antiviral therapy (peginterferon and Ribavirin). Three patients died after transplantation. DISCUSSION: The outcome of liver transplantation in HIV patients was influenced by infections (HCV, CMV, and EBV) and Kaposi's Sarcoma. HCV recurrence was more aggressive, showing a faster progression in this patient population. Drug interaction between HAART and immunosuppressants occurs; longer follow-up and better experience may improve the management of these drug interactions.

2008 - Incidence and clinical outcomes of ventilator-associated pneumonia in liver transplant and non-liver transplant surgical patients. [Articolo su rivista]
C. M., Pellegrino; M., Codeluppi; S., Assenza; S., Cocchi; DI BENEDETTO, Fabrizio; Girardis, Massimo
abstract

The aim of this study was to compare the incidence of ventilator-associated pneumonia (VAP) and clinical outcome among patients undergoing orthotopic liver transplantation (OLT) admitted to our surgical intensive care unit (ICU). Patients with an ICU stay longer than 4 days who had undergone surgery within 48 hours of admission were included in the study. Patients were subdivided into a liver transplant group (OLT) and no-liver transplant group (noLT). Diagnosis of VAP was based on microbiological data with a positive culture from a sample collected >or=48 hours after admission. VAP was defined as early if the positive culture occurred within the 4th day of admission, and late if after the 4th day. Three hundred seventy-three noLT and 71 OLT patients showed no differences in sex, mean severity score on admission (SAPS II), length of stay, and outcomes. The incidence of VAP was also similar in the 2 groups (27.3\% in the noLT group vs 25.3\% in the OLT group). Both in the OLT and noLT groups, the VAP patients showed higher (P< .05) SAPS II scores on admission, length of ICU stay, and mortality rates than the non-VAP patients, without any difference between the 2 groups. VAP is a frequent complication in ICU surgical patients, particularly those with high severity scores on admission. In an ICU surgical population, liver transplantation per se does not seem to increase the patients' risk either for VAP acquisition or for bad outcomes.

2008 - Intermittent gastric outlet obstruction due to a gallstone migrated through a cholecysto-gastric fistula: A new variant of "Bouveret's syndrome" [Articolo su rivista]
Arioli, Dimitriy; Venturini, I; Masetti, Michele; Romagnoli, Elisa; Scarcelli, A; Ballesini, Pietro; Borghi, Athos; Barberini, Alessandro; Spina, Vincenzo; Desantis, M; DI BENEDETTO, Fabrizio; Gerunda, Giorgio Enrico; Zeneroli, Maria Luisa
abstract

Bouveret's syndrome, defined as gastric outlet obstruction due to a large gallstone, is still one of the most dramatic biliary gallstone complications. Although new radiological and endoscopic techniques have made pre-surgical diagnosis possible in most cases and the death rate has dropped dramatically, "one-stage surgery" (biliary surgery carried out at the same time as the removal of the gut obstruction) should be still considered as the gold standard for the treatment of gallstone ileus.In this case, partial gastric outlet obstruction resulted in an atypical and insidious clinical presentation that allowed us to perform the conventional one-stage laparatomic procedure that completely solved the problem, thus avoiding any further complications.

2008 - Is laparoscopic adrenalectomy safe and effective for adrenal masses larger than 7 cm? [Articolo su rivista]
G., Ramacciato; P., Mercantini; M. L., Torre; DI BENEDETTO, Fabrizio; G., Ercolani; M., Ravaioli; M., Piccoli; G., Melotti
abstract

BACKGROUND: Laparoscopic adrenalectomy (LA) has become the gold standard treatment for small (less than 6 cm) adrenal masses. However, the role of LA for large-volume (more than 6 cm) masses has not been well defined. Our aim was to evaluate, retrospectively, the outcome of LA for adrenal lesions larger than 7 cm. PATIENTS AND METHODS: 18 consecutive laparoscopic adrenalectomies were performed from 1996 to 2005 on patients with adrenal lesions larger than 7 cm. RESULTS: The mean tumor size was 8.3 cm (range 7-13 cm), the mean operative time was 137 min, the mean blood loss was 182 mL (range 100-550 mL), the rate of intraoperative complications was 16\%, and in three cases we switched from laparoscopic procedure to open surgery. CONCLUSIONS: LA for adrenal masses larger than 7 cm is a safe and feasible technique, offering successful outcome in terms of intraoperative and postoperative morbidity, hospital stay and cosmesis for patients; it seems to replicate open surgical oncological principles demonstrating similar outcomes as survival rate and recurrence rate, when adrenal cortical carcinoma were treated. The main contraindication for this approach is the evidence, radiologically and intraoperatively, of local infiltration of periadrenal tissue.

2008 - Kaposi's sarcoma after liver transplantation [Articolo su rivista]
DI BENEDETTO, Fabrizio; Di Sandro, S; De Ruvo, N; Berretta, M; Masetti, Michele; Montalti, R; Ballarin, Roberto; Cocchi, S; Potenza, Leonardo; Luppi, Mario; Gerunda, Giorgio Enrico
abstract

INTRODUCTION: Kaposi's Sarcoma (KS) is a malignant neoplasm arising from endothelial cells. HHV8-infection represents a key pathogenic determinant for the development of KS. There are no standard criteria to treat KS in immunosuppressed-individuals. Six cases (2.1%) of KS occurred in our Center among 285-recipients who underwent liver transplantation (LT) between October 2000 and November 2006. METHODS: Patients were four males and two females. Mean age was 57 years (range 44-65). Indication for LT was ESLD associated/non-associated with hepatocellular carcinoma (HCC). The immunosuppressive regimen consisted of cyclosporine/tacrolimus associated with steroids or daclizumab. HHV8-detection was performed by the serological method before LT, and by polymerase chain reaction (PCR)-analysis after KS. RESULTS: One patient had HCV-related cirrhosis and coinfection from HIV, three had HBV-related cirrhosis, two of these with coexistent HCC. The last two patients had alcoholic-cirrhosis, one with coexistent HCC. Mean time from transplantation to KS was 6.2 months (range 3.8-8.8). Three patients were treated with doxorubicin and three with switch from calcineurin-inhibitors to sirolimus. Three patients expired after 11.5, 8.8, and 7.4 months from KS diagnosis. DISCUSSION: KS should be treated by a multidisciplinary approach to obtain an early diagnosis and best management. Effective treatment with immunosuppression reduction or switch to sirolimus is mandatory and can induce complete regression.

2008 - Metachronous liver metastases and resectability: Fong's score and laparoscopic evaluation. [Articolo su rivista]
G. L., Destri; DI BENEDETTO, Fabrizio; B., Torrisi; T. R., Portale; F., Mosca; R., Vecchio; A. D., Cataldo; S., Puleo
abstract

The aim of this retrospective study was to establish whether Fong's risk score can predict rate of resectability and whether laparoscopic exploration with ultrasonography can reduce the number of useless laparotomies to any extent.Fong's score was calculated for each of the 43 potential resectable patients. We analysed: the relation between score and resectability; the probability of unnecessary laparotomy with respect to each level of score; and which of the five Fong parameters was the most indicative of non-resectability. None of our patients was submitted to preoperative laparoscopic staging.All patients with Fong's score 0 were submitted to liver resection, whereas only 76.9\% with score 1, 58.3\% with score 2, and 66.6\% with score 3. No patients had score 4 and 5. "CEA level" is the parameter that best predicts the "non-resectability" of metastases. In the subgroup with score 0-1, laparoscopy would have spared 12\% of unnecessary laparotomies, whereas in subgroup 2-3 this percentage would have risen to 38.9.The above data allowed us to quantify statistically the risk associated with non-resectability of liver metastases in a directly proportional manner as the score progresses.

2008 - Model for End-Stage Liver Disease (MELD) system to allocate and to share livers: experience of two Italian centers. [Articolo su rivista]
M., Ravaioli; M., Masetti; A., Dazzi; A., Romano; Spaggiari, Mario; G. L., Grazi; G., Ercolani; M., Cescon; P. D., Gioia; N. D., Ruvo; R., Montalti; Ballarin, Roberto; DI BENEDETTO, Fabrizio; L., Ridolfi; N., Alvaro; G., Ramacciato; C., Morelli; Gerunda, Giorgio Enrico; A. D., Pinna
abstract

BACKGROUND: The use of the Model for End-stage Liver Disease (MELD) score to prioritize patients on liver waiting lists and to share organs among centers was effective according to US data, but few reports are available in Europe. MATERIALS AND METHODS: We evaluated the outcome of 887 patients listed between April 2004 and July 2006 in a common list by two transplant centers (University of Bologna [BO] and University of Modena [MO] ordered according to the MELD system. Patients with hepatocellular carcinoma had a score calculated according to their real MELD, tumor stage, and waiting time. RESULTS: Five hundred eighty-six (67\%) patients were listed from BO and 291 (33\%) from MO. The clinical features of recipients (sex, age, blood group, and real MELD) were comparable between centers. The number of liver transplantations performed was 307, and 273 (89\%) recipients had a calculated MELD >or=20. Liver transplantations were equally distributed according to the number of patients listed: 215 out of 586 (36.7\%) for BO and 92 out of 291 (31.6\%) for MO. The median real MELD of patients transplanted was 20, and 246 out of 307 (80.1\%) grafts transplanted were functioning. The dropouts from the list were 124 (14\%), and 87 (70\%) of these patients had a calculated MELD >or=20. CONCLUSION: The MELD system was effective to share livers among the two Italian centers. According to this policy, livers were allocated to the recipients with the highest probability of dropout and who had a satisfactory survival after liver transplantation.

2008 - Temporary porto-caval shunt utility during orthotopic liver transplantation. [Articolo su rivista]
Arzu, Gd; Deruvon, ; Montalti, R; Masetti, Michele; Begliomini, Bruno; DI BENEDETTO, Fabrizio; Rompianesi, Gianluca; Disandro, S; Smerieri, Nazareno; D'Amico, Giuseppe; Vezzelli, Elena; Iemmolo, Rm; Romano, Antonio; Ballarin, Roberto; Guerrini, Gian Piero; Deblasiis, Mg; Spaggiari, Mario; Gerunda, Giorgio Enrico
abstract

INTRODUCTION: In liver transplantation (OLT) a porto-caval shunt is a well-defined technique practiced by many surgeons in several centers. METHODS: We considered 186 cadaveric OLT patients who underwent a cavo-cavostomy-type reconstruction; they were divided into two groups: those in whom we performed a porto-caval shunt (group A) and those in whose we did not (group B). We evaluated several variables: warm and total ischemia time, intraoperative blood and fresh frozen plasma transfusions, crystalloid and colloid requirements, blood loss, operative duration, hemodynamic intraoperative changes and diuresis, length of hospital stay, and creatinine values at days 1 and 2, and at discharge day. RESULTS: Total and warm ischemic time differed significantly between the two groups. Infusion of blood, fresh frozen plasma, colloid, and crystalloid did not significantly differ. Blood loss was lower, and intraoperative diuresis was not significantly increased in group A subjects. Postoperative hospitalizations were 16.5 and 17.8 days and operative times, 504 and 611 minutes in the two groups. Both cardiac index and ejection fraction values during the anhepatic phase were significantly greater among group A than group B patients. PAD at the two phases was greater in group B. The PAS was significantly different only at reperfusion time. Creatinine values were significantly different at discharge. Better survival was shown for group A patients over group B subjects. CONCLUSION: The results presented herein confirmed that a porto-caval shunt during OLT was a safe, useful expedient contributing to an improved hemodynamic status and a better time distribution in the various phases of liver transplantation.

2008 - Unusual presentation of metastatic hepatocellular carcinoma in an HIV/HCV coinfected patient: case report and review of the literature. [Articolo su rivista]
M., Berretta; E., Zanet; DI BENEDETTO, Fabrizio; C., Simonelli; A., Bearz; A., Morra; S., Bonanno; S., Berretta; U., Tirelli
abstract

Hepatocellular carcinoma (HCC) is an increasing cause of mortality in human immunodeficiency virus (HIV) seropositive patients. Concurrent infection with HIV may accelerate the progression from cirrhosis to HCC. Viral hepatitis and alcohol abuse are the main risk factors for HCC in developed countries. Exposure to these risk factors is common among HIV-infected patients. We report the case of a 43-year-old woman affected by HCC, with unusual soft tissue metastases (left masseter muscle) and HIV/HCV coinfection. The usual route of metastatic spread from classic HCC is hematogenous, with the most common extrahepatic site being the lung. Our case, besides the unusual distant metastatic site, showed very rapid clinical progression, as has been commonly observed in HIV-infected patients with HCC. The case series of HCC in HIV-positive individuals published to date does not cumulatively exceed 70 subjects.

2007 - Adult liver transplantation in HIV-infected patients [Abstract in Rivista]
Masetti, Michele; Guaraldi, Giovanni; Romano, A; DI BENEDETTO, Fabrizio; Cocchi, S; De Ruvo, N; Codeluppi, M; De Blasiis, Mg; Lemmolo, Rm; Montalti, R; Gerunda, Giorgio Enrico
abstract

Report of a retrospective analysis of the results of adult liver transplantation in HIV-infected patients performed between Jun 2003 and October 2006.

2007 - Adult liver transplantation in HIV-infected patients: Single center experience. [Abstract in Rivista]
Masetti, Michele; Guaraldi, Giovanni; Romano, A; DI BENEDETTO, Fabrizio; De Ruvo, N; Cocchi, S; Codeluppi, M; Guerrini, Gp; Montalti, R; Iemmolo, R; Gerunda, Giorgio Enrico
abstract

Report of a retrospective analysis of the results of adult liver transplantation in HIV-infected pts performed between 6-2003 and 10-2006.

2007 - Adult-to-adult living donor liver transplantation using left lobes: the importance of surgical modulations on portal graft inflow. [Articolo su rivista]
A., Lauro; T. D., Uso; Quintini, Cristiano; DI BENEDETTO, Fabrizio; A., Dazzi; N. D., Ruvo; M., Masetti; Cautero, Nicola; A., Risaliti; C., Zanfi; G., Ramacciato; Begliomini, Bruno; A., Siniscalchi; C. M., Miller; A. D., Pinna
abstract

BACKGROUND: Due to the shortage of available cadaveric organs, living donor liver transplantation (LDLT) has been recently applied extensively in adults. The use of the left lobe should be encouraged because of donor safety, but frequently the metabolic requirements of severely cirrhotic patients are great and subsequent graft dysfunction is encountered after transplantation. The importance of increased portal inflow to the graft in previously severely cirrhotic patients and other hemodynamic changes in LDLT using left lobes are still under debate, as are the surgical modulations to correct them. In this study, we have reported an initial series of adult-to-adult LDLT using left lobes, underlining the hemodynamic changes encountered during the transplant and the surgical modulations we applied to correct them. METHODS: Eight adult recipients underwent left lobe liver transplantation from living donors. Portal vein pressure and central venous pressure were measured before and after surgical modulation. RESULTS: We encountered four cases of small-for-size syndrome. Two patients were retransplanted; the other two died. Seventy-five percent of our recipients survived and 50\% did not require further surgery. CONCLUSION: Surgical portal inflow modulation should be considered in cases of left lobe liver transplantation between adults.

2007 - Bloodstream infections complicating orthotopic liver transplant: comparison between the recipients from cadaver and living donors [Abstract in Rivista]
A., Bedini; C., Venturelli; M., Codeluppi; S., Cocchi; F., Prati; DI BENEDETTO, Fabrizio; Masetti, Michele; Mussini, Cristina; Guaraldi, Giovanni; V., Borghi; F., Rumpianesi; Gerunda, Giorgio Enrico; R., Esposito
abstract

We evaluated the incidence, the prevalence of the microorganisms isolated and the impact on the survival of the bloodstream infections in two groups of patients: recipients of orthotopic liver transplant from cadaveric donor and from living donor.

2007 - Cetuximab/targeted chemotherapy in an HIV-positive patient with metastatic colorectal cancer in the HAART era: A case report [Articolo su rivista]
M., Berretta; F., Martellotta; C., Simonelli; DI BENEDETTO, Fabrizio; N. D., Ruvo; A., Drigo; A., Bearz; M., Spina; E., Zanet; S., Berretta; U., Tirelli
abstract

Recent data have shown the efficacy of cetuximab/Folfiri regimen in patients with chemotherapy-resistant metastatic colorectal cancer. In the literature there are no data about this treatment in HIV-positive patients with metastatic colorectal cancer. At the Aviano Cancer Center, we used the cetuximab/Folfiri regimen and concomitant HAART in an HIV-positive patient with metastatic colorectal cancer. The patient experienced acceptable non-hematological toxicity, without any opportunistic infection and his HIV infection was kept under control. This case suggests that, in the HAART era, a multidisciplinary approach can be offered to HIV patients with advanced cancer when they have good performance status, resulting in efficacious control of the HIV infection.

2007 - Different dose adjustments of immunosuppresants are necessary after initiating boosted or unboosted first protease inhibitors regimen post-liver transplantation [Abstract in Atti di Convegno]
Guaraldi, Giovanni; Cocchi, S.; Ciaffi, S.; Motta, A.; Pinetti, D.; Codeluppi, M.; Bonora, S.; DI BENEDETTO, Fabrizio; Masetti, M.; Di Sandro, S.; Nardini, Giulia; Bertolini, A.; Gerunda, Giorgio Enrico; Esposito, Roberto
abstract

Antiretroviral (ARV) drug interactions in HIV-infected liver transplant (LTx) recipients can lead to increased levels of immunosuppressive agents (Is) which are responsible to induce acute renal failure and other major toxicities.

2007 - Does change of the liver change the metabolism? Assessment of atazanavir pharmacokinetic profile in 7 HIV-infected patients pre- and post-liver transplantation [Abstract in Atti di Convegno]
Cocchi, S.; Guaraldi, Giovanni; Ciaffi, S.; Motta, A.; Pinetti, D.; Codeluppi, M.; Bonora, S.; DI BENEDETTO, Fabrizio; Masetti, M.; Di Sandro, S.; Nardini, Giulia; Zona, S.; Bertolini, A.; Gerunda, Giorgio Enrico; Esposito, Roberto
abstract

Liver Transplantation (LTx) is a rational therapeutic option for selected HIV-infected patients who have concomitant end-stage liver disease (ESLD). In particular, the use of atazanavir (ATV) in the setting of patients with HIV infection suffering from ESLD is actually controindicated.

2007 - Gram-positive bloodstream infections in liver transplant recipients: incidence, risk factors, and impact on survival. [Articolo su rivista]
A., Bedini; M., Codeluppi; S., Cocchi; Guaraldi, Giovanni; DI BENEDETTO, Fabrizio; C., Venturelli; Masetti, Michele; F., Prati; Mussini, Cristina; V., Borghi; Girardis, Massimo; Gerunda, Giorgio Enrico; F., Rumpianesi; Esposito, Roberto
abstract

The objective of the study was to assess the incidence, risk factors, and survival of gram-positive bloodstream infections (GP-BSIs) among liver transplant recipients during the first year after transplantation. Between October 2000 and September 2006, 42 episodes of GP-BSIs occurred in 205 patients with an overall incidence of 0.20 episodes/patient. Coagulase-negative staphylococci were detected in 45.2% of cases, Enterococcus species in 42.9% (E faecalis, eight; E faecium, seven; E avium, two; E gallinarum, one) and Staphylococcus aureus in 11.9%. Retransplantation was the only independent risk factor for GP-BSI (odds ratio [OR], 0.253; 95% confidence interval (CI), 0.089 to 0.715; P = .009). Thirty-day mortality rate was 28.5% and S aureus infections were related to a poorer outcome. It is noteworthy that all the isolates of S aureus were methicillin-resistant. Ampicillin was inactive against all the strains of E faecium and 50% of E avium isolates, but active against all E faecalis and E gallinarum strains. All the isolates were glycopeptide-susceptible. No significant differences in mortality rate were observed in relation to sex, etiologies of end-stage liver disease, cytomegalovirus infection/reinfection, type of donor, rejection, or retransplantation. GP-BSI, the only independent risk factor for death (OR, 0.262; 95% CI, 0.106 to 0.643; P = .003), reduced the survival rate by 26% in the first year posttransplant. In conclusion, GP-BSIs impact significantly on morbidity and mortality posttransplant, particularly among retransplantations. Control measures are required to reduce the incidence of GP-BSIs in liver transplant recipients. These findings must be considered when empirical antimicrobial therapy is indicated while awaiting blood-culture results.

2007 - High dose rabbit antithymocyte globulin induction in living related liver transplantation. [Articolo su rivista]
Masetti, Michele; Montalti, R; Arpinati, M; DI BENEDETTO, Fabrizio; Miller, Cm; Zagnoli, A; Deruvo, N; Guerrini, Gian Piero; Romano, Antonio; Rondelli, D; Chirumbolo, G; Rompianesi, Gianluca; Pinna, Antonio Daniele; Gerunda, Giorgio Enrico
abstract

BACKGROUND/AIMS: Induction with rabbit antithymocyte globulin (RATG) has been reported to be effective in cadaveric liver transplantation. The aim of this study was to compare two immunosuppressive protocols in adult living-related liver transplantation (LRLT). METHODOLOGY: From May 2001 through May 2003, 34 LRLT were performed. The first 17 patients (group 1) were treated with tacrolimus (TAC) and steroids. The next 17 patients (group 2) were treated with a steroid-sparing protocol using RATG. RESULTS: The one-year patient and graft survival was respectively 76.5% and 64.7% for group 1 and 88.2 and 76.5% for group 2 (p = 0.037 and p = NS, respectively). Incidence of acute cellular rejection was 41.2% in group 1 compared to 47% in group 2 (p = NS). Mean daily TAC dose at 6 months was 6.5 +/- 1.1 mg/day in group 1 and 3.2 +/- 0.9 mg/day in group 2 (p &lt; 0.001). In group 1, 41.1% experienced CMV infection compared to 11.7% in group 2 (p = NS). CONCLUSIONS: These results suggest that this approach of RATG induction followed by postoperative, steroid-free, and low-dose TAC is safe and provides for adequate immunosuppression and similar outcome when compared to controls treated with standard TAC and steroid immunosuppression.

2007 - Historical notes: From "Halsted" mastectomy to lumpectomy [Articolo su rivista]
Francescon, M.; Zilio, D.; Panizzo, N.; Di Benedetto, F.; Cedolini, C.
abstract

Since the ancient times breast cancer has always represented a debated theme in terms of its pathogenesis, diagnosis and therapy. The evolution of diagnostic and stadiation instrumental exams allowed us to avoid in many patients extensive demolitive surgery favouring a multidisciplinary conservative treatment. © 2007 by new Magazine edizioni s.r.l.

2007 - Intestinal autotransplantation for adenocarcinoma of pancreas involving the mesenteric root: our experience and literature review. [Articolo su rivista]
Quintini, C; Di Benedetto, F; Diago, T; Lauro, A; Cautero, N; De Ruvo, N; Romano, A; Di Sandro, S; Ramacciato, G; Pinna, Ad.
abstract

Ductal adenocarcinoma of pancreas represents one of the most aggressive tumor as demonstrated by 3- and 5-year survival rates. Involvement of mesenteric pedicle affects both the possibility to perform a tumor-free margin resection and accounts for most exploratory laparotomy for locally advanced disease. The ex vivo resection of the tumor (autotransplantation) after total exenteration and perfusion of the intestine might have a role to overcome some technical obstacles. So far, only 5 patients have been reported to have undergone small-bowel autotransplantation for tumor involving the mesenteric root. We describe 2 cases of adenocarcinoma of pancreas involving mesenteric root treated by small-bowel autotransplantation. Both patients survived from the procedure and were discharged home on postoperative days 16 and 29, respectively. The tumor was resected with free surgical margins, and both patients underwent adjuvant treatment. Intestinal autotransplantation can represent a significant technical advance for increasing the resectability rate and, ultimately, the survival rate for advanced adenocarcinoma of the pancreas in highly selected patients.

2007 - Laboratory test variability and model for end-stage liver disease score calculation: effect on liver allocation and proposal for adjustement. [Articolo su rivista]
Ravaioli, M; Masetti, Michele; Ridolfi, L; Capelli, M; Grazi, Gl; Venturoli, N; DI BENEDETTO, Fabrizio; Bianchi, Fb; Cavrini, G; Faenza, S; Begliomini, B; Pinna, Ad; Gerunda, Giorgio Enrico; Ballardini, G.
abstract

BACKGROUND: The use of the Model for End-Stage Liver Disease (MELD) score to prioritize patients on liver waiting lists must take the bias of different laboratories into account. METHODS: We evaluated the outcome of 418 patients listed during 1 year whose MELD score was computed by two laboratories (lab 1 and lab 2). The two labs had different normality ranges for bilirubin (maximal normal value [Vmax]: 1.1 for lab 1 and 1.2 for lab 2) and creatinine (Vmax: 1.2 for lab 1 and 1.4 for lab 2). The outcome during the waiting time was evaluated by considering the liver transplantations and the dropouts, which included deaths on the list, tumor progression, and patients who were too sick. RESULTS: Although the clinical features of patients were similar between the two laboratories, 36 (13.1%) out of 275 were dropped from the list in lab 1, compared to 5 (3.5%) out of 143 in lab 2 (P&lt;0.01). The differences were mainly due to the deaths on the list (8% lab 1 vs. 2.1% lab 2, P&lt;0.05). The competing risk analysis confirmed the different risk of dropout between the two labs independently of the MELD score, blood group, and preoperative diagnosis. The bias on MELD calculation was considered and bilirubin and creatinine values were "normalized" to Vmax of lab 1 (corrected value=measured value x Vmax lab 1/Vmax lab 2). By comparing receiver operating characteristic curves, the ability of MELD to predict the 6-month dropouts significantly increased from an area under the curve of 0.703 to 0.716 after "normalization" (P&lt;0.05). CONCLUSIONS: Normalization of MELD is a correct and good compromise to avoid systematic bias due to different laboratory methods.

2007 - Liver Transplantation From a Donor Affected by Marfan's Syndrome. [Articolo su rivista]
Benedetto, F. D.; Di Sandro, S.; Ruvo, N.; Masetti, M.; Quintini, C.; Montalti, R.; Ballarin, R.; Gerunda, G. E.
abstract

liver transplantation from a Donor Affected by Marfan's Syndrome.

2007 - Liver transplantation in HIV patients [Abstract in Rivista]
Masetti, M.; Cocchi, S.; Montalti, R.; Guaraldi, Giovanni; Romano, A.; Codeluppi, M.; Girardis, Massimo; De Ruvo, N.; Busani, S.; Ballarin, R.; DI BENEDETTO, Fabrizio; Guerrini, G. P.; Iemmolo, R. M.; Rompianesi, G.; Gerunda, Giorgio Enrico
abstract

not available

2007 - Pancreatic schwannoma of the body involving the splenic vein: Case report and review of the literature [Articolo su rivista]
Di Benedetto, F.; Spaggiari, M.; De Ruvo, N.; Masetti, M.; Montalti, R.; Quintini, C.; Ballarin, R.; Di Sandro, S.; Costantini, M.; Gerunda, Giorgio Enrico
abstract

Pancreatic schwannoma is a rare, benign tumour originating from the Schwann cell. The Schwann cells line the nerve sheath and can give rise to two types of tumours: schwannomas and neurofibromas.

2007 - Quadrantectomy [Articolo su rivista]
Sattin, E.; Di Benedetto, F.; Rossit, L.; Luvisetto, F.; Cedolini, C.
abstract

Breast cancer conservative surgery consists in tumour surgical excision, as the first fundamental step, completed by adjuvant or intraoperative radiotherapy, sentinel node biopsy and chemotherapy or hormonal therapy. Quadrantectomy, as stated by Veronesi, contemplates the excision of the entire quadrant of the breast mound, starting from a skin island centered on the cutaneous tumour projection, continuing with subcutaneous and adipose tissue resection, arriving to the glandular portion including muscular fascia. The resection must guarantee free margins of at least 2 cm. The conservative therapy, for neoplasies at an initial stage, allows to obtain a long term survival rate comparable to patients undergone to radical mastectomy, with less morbidity and acceptable aestethic results. Copyright © 2007 by new Magazine edizioni s.r.l.

2007 - Sirolimus Monotherapy in Liver Transplantation [Articolo su rivista]
Benedetto, F. D.; Di Sandro, S.; Ruvo, N. D.; Masetti, M.; Montalti, R.; Romano, A.; Guerrini, G. P.; Ballarin, R.; De Blasiis, M. G.; Gerunda, G. E.
abstract

INTRODUCTION: Since 1999, a new immunosuppressive drug was administered to renal transplant patients. The SRL molecule acts by blocking post-receptor signal transduction of interleukin-2 (IL-2) interacting with a family of intracellular binding proteins termed immunophilins FKBPs. Among these FKBPs, FK506 12-kd binding protein is the most relevant. SRL is an immunosuppressive drug. Therefore it can inhibit the immune system; at the same time the drug is not nephrotoxic, neurotoxic, and without diabetogenic effects. METHODS: Among 285 patients who underwent liver transplantation, 27 took Sirolimus as monotherapy. Immunosuppressive treatment upto cyclosporine (CsA) or tacrolimus (FK) associated with steroids (methylprednisolone) and mycophenolate Mofetil (MMF) was initiated among subjects with pre-transplant renal failure. SRL was administered as monotherapy for patients who developed nephrotoxicity, or neurotoxicity, or diabetes. Moreover, patients affected by multifocal HCC who did not meet the Milan criteria or patients who developed Kaposi's Sarcoma were prescribed SRL monotherapy. RESULTS: Nephrotoxicity occurred in 14 patients with mean serum creatinine level 2.2 mg/dl. Eleven patients with real failure showed significant improvements after a mean period of 28 days of SRL monotherapy (range: 6-45 days). The mean creatinine serum level after treatment with SRL monotherapy was 1.0 mg/dl (range: 0.7-1.2 mg/dl). Neurotoxicity occurred in 4 patients with tremor, confusion, and agitation. Each patient had complete improvement of symptoms after a few days of Sirolimus monotherapy. Among Three patients who developed Kaposi's Sarcoma, two underwent remission. One patient had diabetes due to calcineurin inhibitors, and one showed arterial hypertension not treatable with drugs. After the switch, we treated these patients with medications. Another important indication was HCC not meeting the Milan criteria. CONCLUSION: SRL monotherapy may be used to manage complication of calcineurin inhibitors or Kaposi's Sarcoma.

2007 - Successful liver transplantation using a severely injured graft. [Articolo su rivista]
Benedetto, F. D.; Quintini, C.; Ruvo, N. D.; Masetti, M.; Cautero, N.; Lauro, A.; Uso', T. D.; Guerrini, G.; Di Sandro, S.; Miller, C. M.; Pinna, A. D.; Gerunda, G. E.
abstract

No abstract available.

2007 - The sentinel node biopsy [Articolo su rivista]
Rossit, L.; Sattin, E.; Di Benedetto, F.; Molaro, R.; Cedolini, C.
abstract

Sentinel node biopsy is an effective procedure in breast cancer stadiation. This technique consists in injection of a radioactive agent and a dying substance in the peritumoral zone. The radioactive agent ad the dyer will drain to the first nodes of the regional lymphatic basin, called sentinel node. After its detection with the use of a gamma probe nodes are harvested and histologically examined. The aim of this technique is to evaluate the extension of the disease and to avoid the patient, in the case of negative sentinel node biopsy, axillary nodes dissection, with its complications. © 2007 by new Magazine edizioni s.r.l.

2007 - Transarterial chemoembolisation for hepatoblastoma [Articolo su rivista]
Di Cataldo, A.; Di Benedetto, F.; Bertuna, G.; Scalisi, F.; Petrillo, G.
abstract

The case reported is of a 13-month-old baby boy with hepatoblastoma which became resectable after chemotherapy but surgery had to be postponed. Alphafetoprotein increased and transarterial chemoembolisation was safely performed, followed by resection. He remains in remission 40 months later. Chemoembolisation is a feasible procedure even in very young patients with hepatoblastoma.

2006 - A new reconstruction of the accessory donor right hepatic artery with interposition of the SMA in liver transplantation [Articolo su rivista]
DI BENEDETTO, Fabrizio; Cautero, Nicola; De, RUVO N; Masetti, Michele; Montalti, R; Gerunda, Giorgio Enrico; Quintini, Cristiano
abstract

One of the most common anatomic variation of the donor hepatic artery in liver transplantation is presence of an accessory right hepatic artery arising from the superior mesenteric artery (SMA). Several methods for reconstruction have been described.1-3

2006 - Bloodstream infections (BSIs) in Liver Transplant Recipients: Analisys at an Italian Tertiary-Care Hospital [Abstract in Atti di Convegno]
Bedini, A.; Cocchi, S.; DI BENEDETTO, Fabrizio; Codeluppi, M.; Guaraldi, Giovanni; Venturelli, C.; Mussini, Cristina; Prati, F.; Masetti, M.; Rumpianesi, F.; Gerunda, Giorgio Enrico; Esposito, Roberto
abstract

After liver transplantation, bacteriemia has been documented in 24% to 35%.We evaluated the incidence of BSIs and the impact on the survival in 205 consecutive liver-transplant recipients at the University Hospital of Modena-Italy

2006 - Don't deny liver transplantation to HIV patients with hepatocellular carcinoma in the highly active antiretroviral therapy era. [Articolo su rivista]
Benedetto, F. D.; Ruvo, N. D.; Berretta, M.; Masetti, M.; Montalti, R.; Di Sandro, Stefano; Quintini, C.; Codeluppi, M.; Tirelli, U.; Gerunda, G. E.
abstract

In an era of highly active antiretroviral therapy(HAART), liver transplantation is becoming an effective therapy inHIV patients suffering from hepatitis C virus (HCV)/hepatitis B virus(HBV) cirrhosis.1 The increase in survival of patients with HIV infection,attributed to HAART, has prompted the medical community toconsider therapeutic strategies including the possibility of major surgeryand solid organ transplantation to contrast the clinical picture ofend organ failure.In this clinical setting, several studies have consistently associatedan increased risk of death as a result of hepatocellular carcinoma(HCC) with HIV infection.2 In a large French survey, HCC-relateddeath in HIV patients rose from 11% in 1997 to 25% in 2001.3 Moreover,some reports have emphasized a more aggressive course ofHCCwith respect to HCC seen in HIV-negative individuals.4,5 In particular,the HCC is diagnosed at a younger age, and is generally more advanced(infiltrating ormetastatic) at diagnosis.6 Recent evidences suggesta crucial role of the HIV TAT protein to drive hepatocarcinogenesis inpatients with virus- or alcohol-mediated cirrhosis7,8; a coexistent weakerantitumor response because of a chronically low CD4 and CD8 lymphocytecounts must also be kept in due consideration. Consequently, amorefrequentscreeningthanevery6monthshasbeenwarrantedbecauseof the swifter course of HCC

2006 - Fatal cytomegalovirus necrotising enteritis in a small bowel transplantation adult recipient with low pp65 antigenaemia levels [Articolo su rivista]
S., Cocchi; DI BENEDETTO, Fabrizio; M., Codeluppi; Guaraldi, Giovanni; A., Lauro; A., Bagni; M., Pecorari; W., Gennari; Quintini, Cristiano; Esposito, Roberto; Ad, Pinna
abstract

Although advances in immunosuppressive therapy have led to increased survival of solid organ transplantation recipients, it is well established that current protocols have been associated with an increased risk of developing tissue-invasive infections. In particular, cytomegalovirus still represents an important cause of morbidity. We report a case of cytomegalovirus infection involving the graft ileum with documented necrotising enteritis that developed after small bowel transplantation. The patient, a 56-year-old Caucasian female with a postsurgery short bowel syndrome, underwent a small bowel transplantation. Immunosuppression was maintained by combination of tacrolimus, steroids and daclizumab. Both the donor and the recipient were serologically negative for cytomegalovirus IgG. Nevertheless, ganciclovir prophylaxis was given for 21 days after surgery, as standard procedure. On hospital day 174, routine pp65 antigenaemia resulted positive (14/200,000 peripheral blood leukocytes). The patient was asymptomatic and preemptive ganciclovir therapy was instituted. In the following 3 days, due to a cytomegalovirus antigenaemia increase, ganciclovir was changed to foscarnet with subsequent virological response (7/200,000 peripheral blood leukocytes, on day 18 1). Two days later, the patient complained of acute abdominal pain and she underwent surgery for the diagnosis. Since the intraoperative findings consisted of a diffuse acute purulent peritonitis, the intestinal graft, together with native rectum, was removed. Biopsy specimens showed evidence of tissue-invasive cytomegalovirus infection. Postsurgery, the patient developed septic shock and died on day 198 as a consequence of multiple organ failure.

2006 - Giant cell hepatitis following primary infection with HHV-6 variant A, transmitted from the donor, in a liver transplant recipient latently infected with HHV-6 variant B [Abstract in Rivista]
Guaraldi, Giovanni; Cocchi, S; Codeluppi, M; Pecorari, M; Barozzi, P; Gennari, W; Bagni, A; Bosco, R; Vallerini, D; DI BENEDETTO, Fabrizio; Masetti, Michele; Portolani, M; Torelli, G; Luppi, Mario
abstract

Syncytial giant-cell hepatitis is a rare but severe form of hepatitis that is associated with autoimmune diseases, drug reactions, and viral infections. We used serologic, molecular, and immunohistochemical methods to search for an infectious cause in a case of syncytial giant-cell hepatitis that developed in a liver-transplant recipient who had latent infection with variant B of human herpesvirus 6 (HHV-6B) and who had received the organ from a donor with variant A latent infection (HHV-6A).

2006 - Hepatic hilum management in 250 liver-multivisceral procurements [Articolo su rivista]
Di Benedetto, F; De, RUVO N; Masetti, M; Cautero, N; Lauro, A; Montalti, R; Quintini, C; Di Francesco, F; Romano, A; Guerrini, G; Ballarin, R; Molteni, G; Spaggiari, M; Sandro, Di; Gerunda, G.
abstract

An accurate in vivo preparation of the hepatic hihim is a fundamental prerequisite for a successful multiorgan transplantation. Our preferred technique in this surgical setting is in vivo procurement in the heart-beating donor. This technique allows an effective exposition of the hilum structures and recognition of anatomical vascular variants, particularly those of the hepatic artery. Also, the cold ischemia time is drastically reduced, and the back-table preparation is left to a minimum. In this article we show the results of a consecutive series of 250 procurements.

2006 - Impact of biliary complications in right lobe living donor liver transplantation. [Articolo su rivista]
G., Ramacciato; G., Varotti; Quintini, Cristiano; Masetti, Michele; DI BENEDETTO, Fabrizio; G. L., Grazi; G., Ercolani; M., Cescon; M., Ravaioli; A., Lauro; A., Pinna
abstract

Biliary reconstruction is one of the most challenging parts of right lobe living donor liver transplantation (RL LDLT), and biliary complications have been reported as the first source of surgical complications of this procedure. We reviewed biliary reconstruction and complications in 27 consecutive RL LDLTs. We compared the first 14 procedures (group 1) to the last 13 (group 2). Seven patients (25.9\%) experienced a biliary complication (five leaks and two strictures). The incidence of biliary complications was 11.1\% in RL grafts with a single duct and 55.5\% in graft presenting multiple bile ducts (P = 0.03). Four of the 18 patients with a duct-to-duct reconstruction (22.2\%) and three of the 11 patients with a Roux-en-Y reconstruction (27.3\%) developed a biliary complication (P = ns). The incidence of biliary complications significantly decreased from 42.9\% (n = 6) in the first group to 7.6\% (n = 1) in the second group (P = 0.05). The overall 1-year graft and patient survival were 57.1\% and 64.3\% in group 1 versus 100.0\% and 100\% in group 2 (P = 0.01; P = 0.006). Biliary complications remain one of the most important technical complications affecting RL LDLT. Nevertheless, attention and surgical refinement can lead to a significant reduction of the biliary complication rate, improving graft and patient survival.

2006 - Left lobes in adult to adult LDLT: The importance of surgical modulations in portal craft inflow. A single center experience. [Relazione in Atti di Convegno]
Lauro, A; Uso, Td; Dazzi, A; Siniscalchi, A; Quintini, C; DI BENEDETTO, Fabrizio; Masetti, Michele; Cautero, Nicola; De Ruvo, N; Risaliti, A; Ramacciato, G; Begliomini, Bruno; Miller, Cm; Pinna, Ad
abstract

LEFT LOBES IN ADULT TO ADULT LDLT: THE IMPORTANCE OF SURGICAL MODULATIONS IN PORTAL GRAFT INFLOW. A SINGLE CENTER EXPERIENCE. Augusto Lauro1, Teresa Diago Usò2, Alessandro Dazzi1, Antonio Siniscalchi1, Cristiano Quintini2, Fabrizio Di Benedetto2, Michele Masetti2, Nicola Cautero2, Nicola De Ruvo2, Andrea Risaliti2, Giovanni Ramacciato1, Bruno Begliomini2, Charles M. Miller2, Antonio D. Pinna1. 1Liver and Multiorgan Transplant Unit, Policlinico Sant’Orsola-Malpighi, University of Bologna, Bologna, Italy; 2Liver and Multivisceral Transplant Center, Policlinico of Modena,University of Modena and Reggio Emilia, Modena, Italy Background Due to shortage of cadaveric organs, living donor liver transplantation (LDLT) has been recently applied extensively to adults. The use of left lobes should be encouraged because of donor’s safety, but the metabolic requirements of severely cirrhotic patients are superior and a subsequential graft dysfunction as small for size syndrome(SFSS) is often encountered after transplantation. The importance of increased portal inflow to the graft in LDLT using left lobes are still under debate, and so the surgical modulations used to correct them. Aims We report our initial series of adult to adult LDLT using left lobes, underlining the haemodynamic changes encountered during the transplant and the surgical modulations we applied in order to correct them. The clinical outcome of the grafts was analyzed,with 2 years follow-up. Patients Eight adult recipients underwent left lobe liver transplantation from living donor. Methods Portal vein pressure(PVC) and central venous pressure(CVP) were measured before and after surgical modulation by central line and inferior mesenteric vein (IMV) catheterization.The differential pressures between PVC and CVP analyzed before and after the transplant (r Pre and r Post) were reported.The surgical manoeuvres performed during the transplant were represented by splenectomy and vascular shunts. Results We developed 3 cases of small for size syndrome(SFSS). Two patients were retransplanted, three died. One patient underwent a third transplant for HCV recurrence and died in post-operative period. After 2 years follow-up 66% of recipients survived and 80% of them did not require any further surgery. Conclusion Liver volume, and GRWR, is not the only factor in producing a SFSS after adult to adult LDLT using left lobes. Surgical portal inflow modulation should be considered in case of left lobe liver transplantation between adults: recipients with a higher GRWR with severe portal hypertension can beneficiate of surgical modulations to avoid SFSS and obtain graft functionality.

2006 - Liver resection of metastasis by colorectal cancer in a HIV patient [Articolo su rivista]
DI BENEDETTO, Fabrizio; De Ruvo, N; Masetti, Michele; Cautero, Nicola; Quintim, C; Montalti, R; Gerunda, Giorgio Enrico; Guaraldi, Giovanni; Tirelli, U; Berretta, M.
abstract

Liver resection has become the treatment of choice for liver metastasis after colorectal cancer. However, HIV patients have been long denied this chance of cure. The increase in survival of patients with HIV infection is attributed to the use of highly active antiretroviral therapy (HAART). The changes in natural history have prompted the medical community to consider therapeutic strategies including the possibility of major surgery and solid organ transplantation to contrast the clinical picture of end-organ failure or malignancies with a poor prognosis.As results in long-term outcome have not been encouraging, surgeons are not willing to get involved in their management, and both oncologists and infectivologists do not often refer these patients to surgeons. From the advent of HAART to the present, we have treated nine HIV patients of which eight were with major surgery (five orthotopic liver transplants, two liver resections and one head pancreatico-duodenectomy) and one was with a large wound hernia repair.

2006 - Multidisciplinary approach in a HIV/HCV-positive patient with liver metastases by colorectal cancer in the HAART era [Articolo su rivista]
Berretta, M; DI BENEDETTO, Fabrizio; Simonelli, C; Bearz, A; Berretta, S; Maugeri, D; Tirelli, U.
abstract

No abstract available

2006 - Oxaliplatin and capecitabine (Xelox) in association with highly active antiretroviral therapy in advanced hepatocarcinoma HIV/HCV-infected patients [Articolo su rivista]
Berretta, M; Lleshi, A; DI BENEDETTO, Fabrizio; Bearz, A; Spina, M; Tirelli, U.
abstract

No abstract available

2006 - Pharmacokinetic interaction between amprenavir/ritonavir and FosAmprenavir on cyclosporine in two patients with human immunodeficiency virus infection undergoing orthotopic liver transplantation [Articolo su rivista]
Guaraldi, Giovanni; S., Cocchi; M., Codeluppi; DI BENEDETTO, Fabrizio; S., Bonora; A., Motta; K., Luzi; M., Pecorari; W., Gennari; Masetti, Michele; Gerunda, Giorgio Enrico; Esposito, Roberto
abstract

The pharmacokinetic interaction between highly active antiretroviral therapy (HAART) and immunosuppressive drugs is a critical element in the management of patients with human immunodeficiency virus infection who undergo orthotopic liver transplantation (OLT). We describe the effect of the coadministration of Amprenavir/Ritonavir (APV/r) and FosAmprenavir (FosAPV) on cyclosporine (CsA) concentrations in two patients receiving OLT for end-stage liver disease due to hepatitis C Virus. Patient 1, who was maintained on 300 mg CsA twice a day with a trough concentration (C-trough) around 250 ng/mL, restarted HAART 12 days after transplantation with 300 mg APV/r twice a day with corresponding APV C-trough of 5293 ng/mL and RTV C-tough of 186 ng/mL. Forty-eight hours after initiation of HAART, C-trogh of CsA was 1200 mg/mL, so it was necessary to reduce the CsA dosage 12-fold (50 mg every day) to achieve a therapeutic effect. In Patient 2, who was maintained on 300 mg CsA twice a day and a corresponding C-trough of 400 ng/mL, HAART was restarted 12 days post-OLT with FosAPV 1400 mg twice a day. After 48 hours C-trough of CsA was around 600 ng/mL and C-trough of FosAPV, 1221 ng/mL. In this case it was necessary to reduce the CsA administration 3.5-fold (175 mg every day). In conclusion, therapeutic drug monitoring was necessary to monitor HAART and CsA post-OLT to prevent toxicity due to both therapies. The use of FosAPV without ritonavir boostering is sufficient to maintain adequate CsA blood concentrations, avoiding any event of toxicity.

2006 - Posttransplant Mycobacterium tuberculosis disease following liver transplantation and the need for cautious evaluation of quantiferon TB GOLD results in the transplant setting: A case report [Articolo su rivista]
M., Codeluppi; S., Cocchi; Guaraldi, Giovanni; DI BENEDETTO, Fabrizio; N., De Ruvo; M., Meacci; B., Meccugni; Esposito, Roberto; Gerunda, Giorgio Enrico
abstract

This report describes a case of pulmonary tuberculosis in a liver transplant patient without a history of previous exposure to Mycobacterium tuberculosis (MTB) complex. Prior to transplantation, the tuberculin skin test was negative and the QuantiFERON-TB Gold (QFT Gold), an, interferon gamma-based blood test, was negative before and after transplant including a period beginning on postoperative day 55 when the patient developed a febrile illness with an interstitial infiltrate and pleural effusion that was unresponsive to broad-spectrum antibiotic therapy. Empiric treatment with isoniazid, ethambutol, and levofloxacin resulted in resolution of the clinical symptoms. A sputum culture grew MTB on postoperative day 87. This case illustrates the need for caution when QFT Gold is used as diagnostic tool for latent tuberculosis during the pretransplant assessment. Further studies evaluating the usefulness of QFT Gold and other interferon gamma tests in posttransplantation active infection are warranted.

2006 - Prognostic factors after surgical resection for hilar cholangiocarcinoma [Articolo su rivista]
G., Ramacciato; N., Corigliano; P., Mercantini; DI BENEDETTO, Fabrizio; Masetti, Michele; G., Ercolani; A., Lauro; N., De Ruvo; A. D., Pinna
abstract

Aims. - To evaluate short and long-term results in 23 patients resected for hilar cholangiocarcinoma. Methods. - Between January 2001 and December 2003, 23 patients with hilar cholangiocarcinoma were resected and considered for retrospective analysis. Univariate and multivariate analysis were performed on several clinicopathological variables in order to evaluate the short-term results. Median follow-up was 11 months (interquartile range 2-20 months). Results. - A major liver resection was performed in 19 out of 23 patients (82%): a right hepatectomy extended to segment 4 in 5 patients and a left hepatectomy in 14 patients. Resection of the caudate lobe was performed in 7 patients (30%). No hospital mortality occurred. Overall morbidity rate was 43%. The 1-year survival rate was 63.2% with a median survival of 19 months. Tumor recurrence appeared in 12 patients (52%). Low preoperative albumin level (P = 0.006), presence of positive resection margin (P = 0.03) and T-stage (P = 0.02) were found to be related to a worse median survival. On multivariate analysis, only the preoperative albumin level and the presence of positive margin were confirmed as independent prognostic factors. Conclusion. - Aggressive surgical approach remains the only potentially curative therapy for the hilar cholangiocarcinoma. Low preoperative albumin level, presence of positive resection margin and T-stage resulted as factors influencing the prognosis after resection.

2006 - Results of intestinal and multivisceral transplantation in adult patients: Italian experience. [Articolo su rivista]
A., Lauro; A., Dazzi; G., Ercolani; M., Cescon; A., D'Errico; M. D., Simone; G. L., Grazi; M., Vivarelli; G., Varotti; N. D., Ruvo; M., Masetti; Cautero, Nicola; DI BENEDETTO, Fabrizio; A., Siniscalchi; Begliomini, Bruno; T., Lazzarotto; S., Faenza; L., Pironi; A. D., Pinna
abstract

PURPOSE: We report our experience with intestinal and multivisceral transplantation in Italy. METHODS: We performed 23 adult isolated intestinal transplants and seven multivisceral ones, three with liver, between December 2000 and June 2005. Indications for transplantation were loss of venous access (n = 14), recurrent sepsis (n = 10), and electrolyte-fluid imbalance (n = 6), 14 of whom also presented with total parenteral nutrition (TPN)-related liver dysfunction. Immunosuppression was based on induction agents like daclizumab (followed by tacrolimus and steroids) in the first period; alemtuzumab or thymoglobulin (with tacrolimus) in a second period after 2002. RESULTS: The mean follow-up was 742 +/- 550 days. Three-year patient actuarial survival rate was 88\% for intestinal transplants and 42\% for multivisceral (P = .015). Three-year graft actuarial survival rate was 73\% for intestinal patients and 42.8\% for multivisceral (P = .1). Graft loss was mainly due to rejection (57\%). Complications were mainly represented by bacterial infections (92\% of patients), relaparotomies (82\%), and rejections (72\%). Full bowel function without any parenteral nutrition or intravenous fluid support was achieved in 60\% of recipients with functioning bowel including 95\% on a regular diet. One patient underwent abdominal wall transplantation as well. DISCUSSION AND CONCLUSION: Intestinal transplantation has achieved high rates of patient and graft survival with even longer follow-up. Early referral of patients, especially in cases of TPN-liver disease, is mandatory to obtain good outcomes and avoid high mortality rates on the transplant waiting list. Immunosuppressive management remains the key factor to increase the success rate.

2006 - Surgical approach to complicated intestinal failure for benign disease in adult patients: transplantation or surgical rehabilitation? [Articolo su rivista]
A., Lauro; C., Zanfi; A., Dazzi; L., Golfieri; A., Amaduzzi; G., Ercolani; M., Cescon; A., Siniscalchi; G. L., Grazi; M., Vivarelli; G., Varotti; M., Ravaioli; M. D., Gaudio; DI BENEDETTO, Fabrizio; A., Cucchetti; G. L., Barba; G., Vetrone; M., Zanello; L., Pironi; S., Faenza; A. D., Pinna
abstract

Surgical approaches to complicated benign intestinal failure are gaining acceptance, especially in the pediatric population. Less international experience has been obtained in adult patients, who are usually treated with total parenteral nutrition (TPN). An intestinal rehabilitation program was started in our institution with comprehensive medical rehabilitation, surgical bowel rescue, and transplantation. Among 38 adult patients referred by our gastroenterologists for bowel rehabilitation and surgically treated in our institution, 92.2\% received TPN on admission. After careful evaluation, 71\% underwent transplantation. Five patients died, but 18 recipients were completely weaned off TPN at follow-up. Eleven patients underwent surgical resection of the affected bowel and a subsequent program of intestinal rehabilitation: they were all alive and weaned off TPN at discharge. At a 2-year mean follow-up, deaths occurred only in the transplant population. Therefore, intestinal surgical rescue, if successful, is optimal in adult patients.

2006 - Univariate and multivariate analysis of prognostic factors in the surgical treatment of hepatocellular carcinoma in cirrhotic patients [Articolo su rivista]
Ramacciato, G; Mercantini, P; Nigri, Gr; Ravaioli, M; Cautero, Nicola; DI BENEDETTO, Fabrizio; Masetti, Michele; Grazi, Gl; Ziparo, V; Ercolani, G; Pinna, Ad
abstract

Background/Aims: Evaluation of the short- and long-term outcome of liver resections for HCC in cirrhotic patients. Methodology: A retrospective analysis was performed on 106 consecutive cirrhotic patients with HCC resected between June 1974 and September 2002. Univariate and multivariate analyses were performed on several clinicopathological variables to analyze factors affecting the long-term outcome and intrahepatic recurrence. Results: Overall mortality and morbidity, were 10.7% and 26% respectively. These rates significantly decreased in the last years: from 1997 to 2002 no hospital mortality has been recorded. After a median follow-up of 19 months (interquartile range: 10-36), tumor recurrence appeared in 25 patients (23.5%). The 1-, 3-, and 5-year overall survival rates were 86.6%, 70.3%, and 60.6%, respectively. The 1-, 3-, and 5-year disease-free survival rates were 86.3%, 58.1%, and 40.7%. Univariate analysis showed that viral etiology of cirrhosis (p=0.03), presence of multiple nodules (P=0.02) and vascular invasion (P=0.05) are related to a worse long-term survival. Multivariate, analysis showed that only the viral etiology of cirrhosis and the presence of multiple nodules were significant independent prognostic factors. Conclusions: Results after hepatic resection for HCC in cirrhotic patients can be improved by using a limited surgical approach. The viral etiology of cirrhosis, the presence of multiple nodules and vascular invasion negatively affected recurrence rate and long-term survival.

2005 - Efficacia di voriconazolo nel trattamento dell’infezione disseminata da Fusarium verticilloides in una paziente sottoposta a ritrapianto di fegato [Abstract in Rivista]
Cocchi, S.; Codeluppi, M.; Guaraldi, Giovanni; DI BENEDETTO, Fabrizio; Venturelli, C.; Masetti, M.; Esposito, Roberto; Gerunda, Giorgio Enrico
abstract

Fusarium species sono responsabili di severe infezioni fungine in pazienti affetti da patologie onco-ematologiche e sottoposti a trapianto di midollo. Tuttavia, solo di rado tali infezioni sono state riportate in altre condizioni di immunodepressione. Descriviamo il caso di una fusariosi disseminata in una paziente sottoposta a ritrapianto di fegato, con revisione dei casi di infezione da Fusarium spp. in soggetti trapiantati di organo solido.

2005 - Liver transplantation for familial amyloid polyneuropathy non-VAL30MET variants: are cardiac complications influenced by prophylactic pacing and immunosuppressive weaning? [Articolo su rivista]
A., Lauro; T. D., Usò; M., Masetti; DI BENEDETTO, Fabrizio; Cautero, Nicola; N. D., Ruvo; A., Dazzi; Quintini, Cristiano; Begliomini, Bruno; A., Siniscalchi; G., Ramacciato; A., Risaliti; C. M., Miller; A. D., Pinna
abstract

BACKGROUND: Cardiac complications represent a cause of morbidity and mortality after liver transplantation among patients with familial amyloid polyneuropathy (FAP), especially for the non-VAL30MET variant types. METHODS: We retrospectively evaluated 11 recipients from a nonendemic area including 90.9\% affected by FAP variants. Preoperative cardiovascular symptoms were present in 81\% of patients. An intraoperative pacemaker was placed prophylactically in 90.9\% of all recipients. Since tacrolimus has been reported in the international literature to display cardiac toxicity, we evaluated the influence of intraoperative prophylactic pacing and rapid postoperative weaning from tacrolimus, mainly allowed by thymoglobulin on the occurrence of posttransplantation cardiac complications. RESULTS: One patient received a combined heart-liver transplant, another, living donor liver transplantation. We did not observe any significant intraoperative cardiac complications. Postoperatively, the pacemaker was removed from all patients but 1. Five patients received tacrolimus and steroids; a subsequent, second group of 6 patients (54.5\%) was treated with thymoglobulin followed by tacrolimus. At discharge the mean tacrolimus level was 10.6 ng/mL, whereas after 1 month it was 7.5 ng/mL. We observed a case of acute cellular rejection before discharge, which was successfully treated with intravenous steroids and OKT3. After a mean follow-up of 17.4 months (range, 1-31), 2 patients had died (18.1\%): 1 due to sepsis and another, to MI. Two recipients experienced cardiac complications (18.1\%), namely, the patient who died due to an myocardial infarction and a second one with a tachyarrhythmia, which was treated successfully with beta-blockers and amiodarone. CONCLUSION: Prophylactic pacing and rapid weaning from immunosuppression are still associated with a significant rate of postoperative cardiac complications.

2005 - Living donor liver transplantation in adult patients : our experience. [Articolo su rivista]
A., Dazzi; A., Lauro; DI BENEDETTO, Fabrizio; Masetti, Michele; Cautero, Nicola; N., De Ruvo; Quintini, Cristiano; G., Ramacciato; C. M., Miller; A. D., Pinna
abstract

Introduction. Living donation in adult liver transplantation (LDLTx) is an important resource because of the waiting list growth. We. started a living donor program to overcome the shortage of cadaveric sources. Patients. From May 2001 to May 2003, 36 patients underwent LDLTx: 27 received a right lobe, 8 received a left lobe, and 1 received segments 11 and III. Results. The 1-year actuarial survival rate was 77.7%, with a mean follow-up, in survivors, of 754 +/- 248 days. Eleven of 27 (40.7%) right lobe recipients died. Among left graft recipients, 3 patients died (33%). We undertook retransplantation in 4 cases, because of 2 small for size syndrome, 1 late hepatic artery thrombosis, and 1 early portal vein thrombosis. After a period of 797 days, all 36 donors returned to a normal social and working life. Two donors, who underwent right lobe donation, experienced major complications: 1 case of biliary stenosis, treated by stenting, and I case of biliary leak from the cut surface of the liver, requiring laparotomy and abscess drainage. Left lobe donors developed no complications. Conclusions. LDLTx has a learning curve for experienced liver transplantation surgeons. Our last 18 cases showed better survivals than the first 18 (9 deaths vs 5), even if, in the latter group, we transplanted 8 left livers. In our experience, LDLTx of a left liver graft has an increased risk of small for size syndrome, but patients, both donors and recipients, report improved outcomes.

2005 - Minimization of immunosuppression with thymoglobuline pre-treatment and HCV recurrence in liver transplantation [Articolo su rivista]
N., De Ruvo; A., Cucchetti; A., Lauro; Masetti, Michele; Di Benedetto, Fabrizio; Cautero, Nicola; G., La Barba; A., Dazzi; F., Di Francesco; G., Molteni; A., Romano; G., Ramacciato; A., Risaliti; A. D., Pinna
abstract

Induction with thymoglobuline, a potent anti-thymocyte polyclonal antibody, has been recently reported to allow minimization of postoperative immunosuppression in organ transplantation. The relationship with recurrence of hepatitis C virus (HCV) after liver transplantation (LTx) has never been investigated. We report here on the outcome in 22 HCV+ patients receiving thymoglobuline pre-treatment and minimal immunosuppression after LTx. Patient survival and acute rejection rates were good, and remarkably low dosages and levels of immunosuppression were achieved with thymoglobuline, without exposing patients to an elevated risk of rejection. A progressive weaning of the primary immunosuppressor was also possible in the majority of patients without complications. The HCV recurrence rate was similar to what is reported in the literature, although lower HCV-RNA viral loads were obtained with thymoglobuline, with a mild histologic course. Although our results need to be validated in large cohort studies, our experience shows that minimization of immunosuppression with thymoglobuline is effective in protecting against rejection and demonstrated a positive impact on HCV recurrence that deserves further investigation.

2005 - Multivisceral harvest with in vivo technique: Methods and results [Articolo su rivista]
Lauro, A; DI BENEDETTO, Fabrizio; Ercolani, G; Masetti, Michele; Cautero, Nicola; Quintini, Cristiano; Dazzi, A; di Francesco, F; Cucchetti, A; Pinna, Ad
abstract

Multivisceral transplants are gaining acceptance worldwide for patients with chronic gastrointestinal failure with or without irreversible total parenteral nutrition (TPN)related liver failure. We describe our experience with nine multivisceral harvests reporting our in vivo technique. Multivisceral grafts included stomach, duodenum, pancreas, small bowel, and part of large intestine with or without the liver. After a careful evaluation of the liver and the bowel, we isolated the superior mesenteric artery origin. Then we identified the distal part of the graft isolating the middle colic vein and stapling the transverse colon to its left. After esophagus isolation and stapling, we mobilized the graft, starting from the spleen to the pancreaticoduodenal block, near the celiac trunk. After cross-clamping and cold perfusion, we created an aortic patch including the superior mesenteric artery and celiac trunk as a multivisceral harvest without the liver. A total hepatectomy is added for a liver multivisceral graft. We harvested four multivisceral grafts without the liver and five multivisceral grafts with the liver. We performed seven multivisceral transplants on adult recipients, four without the liver and three with the liver, as well as two liver and one isolated small bowel transplants. Postreperfusion hemostasis was always satisfactory with a mean ischemia time of 6.5 hours. Four recipients died: there was one intraoperative death due to disseminated intravascular coagulopathy. Another patient underwent graftectomy 1 day after transplantation due to vascular thrombosis. In conclusion, our in vivo technique allows a shorter ischemia time with a minimal postreperfusion bleeding and reduced production of lymphatic ascites, without jeopardizing organ function.

2005 - Outcome in right living related liver transplantation with branch-patch arterial reconstruction [Articolo su rivista]
DI BENEDETTO, Fabrizio; A., Lauro; Masetti, Michele; Cautero, Nicola; Quintini, Cristiano; N., De Ruvo; A., Romano; G., Guerrini; A., Dazzi; G., Molteni; A., Siniscalchi; H., Bertani; Cm, Miller; Ad, Pinna
abstract

Right lobe living liver transplantation is being performed worldwide with increased frequency. Difficult arterial reconstructions are often encountered because of small diameter or discrepancy between arterial stumps. The risk of arterial thrombosis is reported as high as 26%: microsurgical techniques have reduced this rate below 2%, increasing warm ischemia time. We have developed a new branch patch technique in living related liver transplantation using the donor cystic artery to create an enlarged patch anastomosis that enables increase in the vessel's diameter and therefore greater inflow to the liver. We have followed 8 patients treated with this technique. After more than 1 year (mean follow-up: 636 days) we did not observe any arterial thrombosis by Doppler ultrasound performed every 3 months. The mean resistance index was 0.68 (0.57-0.83-). Three patients died with functional graft without signs of thrombosis. We believe that the cystic artery branch patch technique is feasible in all cases. It is fast (mean time: 6.2 min), it allows a shorter warm ischemia time, and there is no increased risk of thrombosis.

2005 - Outcome, incidence, and timing of infectious complications in small bowel and multivisceral organ transplantation patients [Articolo su rivista]
Guaraldi, Giovanni; S., Cocchi; M., Codeluppi; DI BENEDETTO, Fabrizio; N., De Ruvo; Masetti, Michele; C., Venturelli; M., Pecorari; A. D., Pinna; Esposito, Roberto
abstract

Background. Infectious complications still represent a major cause of morbidity and mortality in patients with organ transplantation. In particular, small bowel or multivisceral transplantation is complicated to a greater extent than other grafts as a consequence of infectious complications including sepsis. Methods. This prospective study assessed outcome, incidence, and timing of infections in sequential patients undergoing small bowel or multivisceral transplantation (SB/MVTx) performed at a university transplant center between January 2001 and October 2003. Nineteen patients underwent transplantation during this period, 13 of whom (68%) undergoing isolated SB and 6 (32%) MV grafts with or without liver. Results. The median follow up was 524 days (interquartile range=252-730) with an overall 24.4 person/year of observation. Postoperative mortality rate was 0.1 death/person/year; all patients, except one who died intraoperatively, were alive 6 months postsurgery. There were 100 documented infections including: 59 bacterial (2.4 events/person/year), 35 viral (1.4 events/person/year) and 6 fungal (0.2 events/person/year). Patients developed at least one episode of bacterial infection in 94% of the cases, viral infection in 67%, and fungal infection in 28%. Conclusions. This cohort describes the very common and complex nature of infectious complications in this challenging group of transplantation patients. Larger cohorts are needed to specifically address infection risk factors and longer term outcomes.

2005 - [Outcome of isolated small bowel transplantation in adults: experience from a single Italian center] [Articolo su rivista]
DI BENEDETTO, Fabrizio; A., Lauro; M., Masetti; Cautero, Nicola; N. D., Ruvo; Quintini, Cristiano; S., Sassi; F. D., Francesco; T. D., Usò; A., Romano; A., Dazzi; G., Molteni; Begliomini, Bruno; A., Siniscalchi; L. D., Pietri; Bagni, Alessandra; A., Merighi; M., Codeluppi; Girardis, Massimo; G., Ramacciato; A. D., Pinna
abstract

AIM: Isolated small bowel transplantation is becoming the treatment of choice for adult patients with serious parenteral nutrition (PN) related complications: we report our three-year experience (December 2000-December 2003) from a single Italian center (Modena-Italy), with one of the larger European series. METHODS: We transplanted 14 patients, with a previous mean PN course of 27 months and a mean 21-month post-transplantation follow-up (range 3-36 months), obtaining a one-year actuarial survival rate of 92.3% with no intraoperative deaths. RESULTS: We lost 1 patient (7.2%), died for post-transplantation overwhelming sepsis following Cytomegalovirus (CMV) enteritis. Thirteen patients are alive, with one-year actuarial graft survival rate of 85.1%: 1 patient underwent graft removal (7.2%) for intractable severe acute rejection. Our immunosuppressive regimen was based on tacrolimus and 3 induction protocols: daclizumab (8 patients) with steroids, alemtuzumab (4 patients) and thymoglobulin (2 patients) without steroids. In 9 cases, we added sirolimus. Nine recipients experienced 22 episodes of acute cellular rejection (ACR), treated successfully in all cases but one. One patient (7.2%) was treated successfully for Post Transplant Lymphoproliferative Disease (PTLD) and is disease-free after 8 months. CONCLUSIONS: Small bowel transplantation can achieve optimal results depending on appropriate immunosuppressive management and candidate selection, added to shorter ischemia time and careful donor and graft selection.

2005 - Outcomes after adult isolated small bowel transplantation: experience from a single European centre. [Articolo su rivista]
DI BENEDETTO, Fabrizio; A., Lauro; M., Masetti; Cautero, Nicola; Quintini, Cristiano; A., Dazzi; N. D., Ruvo; T. D., Uso; Begliomini, Bruno; A., Siniscalchi; Bagni, Alessandra; M., Codeluppi; G., Ramacciato; Villa, Erica; A. D., Pinna
abstract

BACKGROUND: Adult isolated small bowel transplantation is considered the standard treatment for patients with life-threatening parenteral nutrition-related complications. Here, we report a 3-year experience in a single European centre between December 2000 and December 2003. AIMS: To evaluate and discuss pre-transplant and post-transplant factors that influenced survival rates in our series. PATIENTS: Fourteen patients, with a mean parenteral nutrition course of 27 months, were transplanted. In eight cases they had not experienced any major complication from parenteral nutrition. METHODS: We described pre-transplant evaluation and inclusion criteria, surgical technique and clinical management after transplant. Immunosuppressive therapy was based on induction drugs and Tacrolimus. We reported survival rates, major complications and rejection events. RESULTS: One-year actuarial survival rate was of 92.3\% with a mean 21-month follow-up (range 3-36 months). We had no intraoperative deaths. One patient (7.2\%) died of sepsis following cytomegalovirus enteritis. One patient underwent graftectomy (7.2\%) for intractable severe acute rejection. One-year actuarial graft survival rate of 85.1\%. One patient (7.2\%) affected by post-transplant lymphoproliferative disease is alive and disease-free after 8 months. CONCLUSION: We believe candidate selection, induction therapy, donor selection and short ischemia time play an important role in survival after small bowel transplantation.

2005 - Preliminary results of a "prope" tolerogenic regimen with thymoglobulin pretreatment and hepatitis C virus recurrence in liver transplantation [Articolo su rivista]
N. D., Ruvo; A., Cucchetti; A., Lauro; M., Masetti; N., Cautero; DI BENEDETTO, Fabrizio; A., Dazzi; M. D., Gaudio; M., Ravaioli; F. D., Francesco; G., Molteni; G., Ramacciato; A., Risaliti; A. D., Pinna
abstract

BACKGROUND: Recent reports demonstrate the efficacy of induction immunosuppression with Thymoglobulin, a potent antithymocyte polyclonal antibody, in allowing acquired tolerance by means of a tolerogenic regimen of recipient pretreatment and low-dose postoperative immunosuppression. The effect of this novel approach on recurrence of hepatitis C viral disease after liver transplantation has never been investigated. We report the preliminary results of a retrospective analysis aimed at discovering any relationship between Thymoglobulin immunosuppression and the pattern of recurrence of hepatitis C. METHODS: Thymoglobulin induction plus tacrolimus monotherapy was used in a group of 22 hepatitis C virus (HCV)+ patients receiving liver transplantation; 30 HCV+ patients receiving transplants within the same year received conventional tacrolimus plus steroid immunosuppression and represented the comparison group. RESULTS: Patient survival and acute rejection rate did not differ between the two groups. Significantly lower dosages and levels of tacrolimus were possible with Thymoglobulin, and a progressive weaning of tacrolimus monotherapy was accomplished in most patients, without major rejection complications. The HCV recurrence rate was similar in both groups, although significantly lower HCV RNA loads were obtained with Thymoglobulin pretreatment. The mean time to histologic recurrence was shorter in Thymoglobulin-treated patients; however, no significant difference was observed in mean Ishak's histologic grading and staging of HCV recurrence. CONCLUSIONS: In our preliminary experience, a "prope" tolerogenic regimen with Thymoglobulin pretreatment and low-dose immunosuppression in liver-transplant recipients gave good protection against rejection and permitted lower HCV viral loads, whose significance in the long-term outcome of HCV patients deserves further investigation.

2005 - Preliminary results of immunosuppression with thymoglobuline pretreatment and hepatitis C virus recurrence in liver transplantation. [Articolo su rivista]
De Ruvo, N; Cucchetti, A; Lauro, A; Masetti, Michele; Cautero, Nicola; DI BENEDETTO, Fabrizio; Dazzi, A; Del Gaudio, M; Ravaioli, M; Zanello, M; La Barba, G; di Francesco, F; Risaliti, A; Ramacciato, G; Pinna, Ad
abstract

Induction with thymoglobulin, a potent anti-thymocyte polyclonal antibody, has been recently reported to allow minimization of postoperative immunosuppression in organ transplantation. The relationship with recurrence of hepatitis C virus (HCV) after liver transplantation (LT) has never been investigated. We report herein on the outcome of 22 HCV+ patients receiving thymoglobulin pretreatment and minimal immunosuppression after liver transplantation. Patient survival and acute rejection rates were good, with remarkably low dosages and levels of immunosuppression achieved with thymoglobulin, and without exposing patients to an elevated risk of rejection. A progressive weaning of the primary immunosuppressant was also possible in the majority of patients without complications. The HCV recurrence rate was similar to that reported in the literature, although lower HCV RNA viral loads were obtained with thymoglobulin and a mild histologic course. Although our results need to be validated in large cohort studies, our experience shows that minimization of immunosuppression with thymoglobulin is effective to protect against rejection and demonstrated a positive impact on HCV recurrence that deserves further investigation.

2005 - Prognostic evaluation of the new American Joint Committee on Cancer International Union Against Cancer staging system for hepatocellular carcinoma: Analysis of 112 cirrhotic patients resected for hepatocellular carcinoma [Articolo su rivista]
Ramacciato, G; Mercantini, P; Cautero, Nicola; Corigliano, N; DI BENEDETTO, Fabrizio; Quintini, Cristiano; Ercolani, G; Varotti, G; Ziparo, V; Pinna, Ad
abstract

Background: In 2002, the American Joint Committee oil Cancer and the International Union Against Cancer redefined the T-classification for hepatocellular carcinoma, shifting the cutoff value for tumor size from 2 to 5 cm and giving more emphasis to vascular invasion. Methods: A retrospective cohor, study was conducted on 223 consecutive patients with hepatocellular carcinoma observed between 1990 and 2002. One hundred twelve were resected and considered for retrospective analysis. Univariate and multivariate analyses were performed on several clinicopathologic variables. After classification according to each staging system. the long-term Survival of different stages was compared. The prognostic value Of each staging system Was further evaluated by entering each stage, in turn, into the Cox regression model with other clinicopathologic variables. The median follow-LIP Was 19 months. Results: On multivariate analysis, the viral etiology of cirrhosis and the presence Of multiple nodules were independent prognostic factors. When the new staging system was entered into the multivariate analysis. it was the only independent factor (P=.02). When stratified according to the old tumor-node-metastasis system, there were no significant differences in the survival between stage I and II (P =.14) or between stage IIIA and IVA (P=.33); only the Survival of stage II and IIIA was different (P <.01). When stratified according to the new tumor-node-metastasis system, then, were significant differences between stage I and II (71.7% vs. 54.7%; P =.02). Conclusions: The new staging system is a more reliable and objective method for T classification. It is easy to use in clinical practice and is better at Stratifying curatively resected patients with respect to prognosis.

2005 - Right ventricular end-diastolic volume index as a predictor of preload status in patients with low right ventricular ejection fraction during orthotopic liver transplantation [Articolo su rivista]
Siniscalchi, A; Pavesi, M; Piraccini, E; De Pietri, L; Braglia, V; DI BENEDETTO, Fabrizio; Lauro, A; Spedicato, S; Dante, A; Pinna, Ad; Faenza, S.
abstract

Objective. The objective of this study was to compare the accuracy of 2 variables: pulmonary artery occlusion pressure (PAOP) and right ventricular end diastolic volume index (RVEDVI) as predictors of the hemodynamic response to fluid challenge as well as definition of the overall correlation between RVEDVI and change in PAOP, right ventricular ejection fraction (RVEF), central venous pressure (CVP), and determination of the right ventricular function during orthotopic liver transplantation. Materials and Methods. A modified pulmonary artery catheter equipped with a fast response thermistor was used to determine RVEF, allowing calculation of RVEF end-diastolic volume index (EDVI, as the ratio of stroke index [SI] to EF). The above-mentioned hemodynamic measures were taken in 4 phases: TO, after induction of anesthesia; T1, during anhepatic phase; T2, 30 ' after graft reperfusion; and T3, at the end of surgery. Results. The variation of the REF value was 36 +/- 4% and 39 +/- 6%. Linear regression analysis showed a significant correlation between RVEDVI (range, 133 +/- 33-145 +/- 40 mL/m(2)) and stroke volume index (SVI) in each phase (r(2) = 0.49, P <.01; r(2) = 0.57, P <.01) at TO and TI, respectively, and at T2 and T3 (r(2) = 0.51, P <.01; r(2) = 0.44, P <.01), respectively. No significant variations in the linear regression analysis between RVEDVI, PAOP, CVP, and RVEF were observed. No relationship was found between PAOP (range, 10 +/- 2-6 +/- 2 mm Hg) and SVI. Conclusion. RVEDVI may be the best clinical estimate of right ventricular preload. In fact, minor changes of RVEF have been recorded, confirming that RV function was not altered during uncomplicated orthotopic liver transplantation.

2005 - Rituximab as treatment of posttransplant lymphoproliferative disorder in patients who underwent small bowel/multivisceral transplantation: Report of three cases [Articolo su rivista]
M., Codeluppi; S., Cocchi; Guaraldi, Giovanni; DI BENEDETTO, Fabrizio; A., Bagni; M., Pecorari; W., Gennari; A. D., Pinna; Gerunda, Giorgio Enrico; Esposito, Roberto
abstract

This report describes three cases of posttransplant lymphoproliferative disorder (PTLD) in multivisceral/small bowel transplant patients treated with rituximab (anti-CD20 monoclonal antibodies). In two cases (one of which was a B-cell lymphoma) a good response to therapy was achieved. A third case (with polymorphic PTLD with low CD20 expression) developed a refractory rejection and PTLD was still documented on graftectomy. Rituximab was well tolerated, and a reduction of Epstein-Barr virus (EBV) viral load was documented by quantitive competitive-EBV polymerase chain reaction. Efficacy of therapy needs to be assessed in controlled studies.

2005 - Role of therapeutic drug monitoring in a patient with human immunodeficiency virus infection and end-stage liver disease undergoing orthotopic liver transplantation [Articolo su rivista]
Guaraldi, Giovanni; S., Cocchi; M., Codeluppi; DI BENEDETTO, Fabrizio; S., Bonora; M., Pecorari; W., Gennari; Cautero, Nicola; A. D., Pinna; Gerunda, Giorgio Enrico; Esposito, Roberto
abstract

Pharmacological interactions between protease inhibitors and tacrolimus require careful monitoring to prevent toxicity in the posttransplantation period. A 42-year-old man with human immunodeficiency virus (HIV) infection and end-stage liver disease due to hepatitis C virus (HCV) received an orthotopic liver transplant. At the time of surgery the patient was on triple antiretroviral therapy (tenofovir, lamivudine, and lopinavir/ritonavir) with a stable CD4+ count (> 500 celIS/mm(3)) and HIV-1 RNA (< 50 copies/mL). Immunosuppression was maintained with tacrolimus (0.5 mg at a single dose once per week). One month after surgery HCV recurrence was documented. Pharmacokinetic evaluation of lopinavir/ritonavir showed a rapid increase in the area under the curve. Drug concentrations returned to normal levels, with reduction in liver enzymes. At the same time, tacrolimus dosages were reduced to a maintenance dose of 0.5 mg every 2 weeks. The patient, at 17 months postoperatively, is alive in good health with normal liver function and HCV RNA load levels. This is the first case in which a profound change in the pharmacokinetics of a protease inhibitor caused by a drug-drug interaction was observed during transient liver damage. Because this clinical event is particularly common in HIV-infected patients, our findings suggest that therapeutic drug monitoring should be performed to determine the impact of potential drug interactions in the early posttransplantation period, at the time of resumption of therapy or introduction of new antiretroviral therapy and during HCV recurrence in order to optimize both tacrolimus and protease inhibitor treatment.

2005 - Small bowel transplantation for diffuse intestinal angiomatosis [Articolo su rivista]
A., Lauro; A., Dazzi; A. D., Pinna; DI BENEDETTO, Fabrizio; Masetti, Michele; Cautero, Nicola
abstract

No abstract available

2005 - Twenty-seven consecutive intestinal and multivisceral transplants in adult patients: a 4-year clinical experience. [Articolo su rivista]
A., Lauro; DI BENEDETTO, Fabrizio; Masetti, Michele; Cautero, Nicola; G., Ercolani; M., Vivarelli; N., De Ruvo; M., Cescon; G., Varotti; A., Dazzi; A., Siniscalchi; Begliomini, Bruno; L., Pironi; M., Di Simone; A., D'Errico; G., Ramacciato; G., Grazi; A. D., Pinna
abstract

Adult isolated intestinal and multivisceral transplantation is gaining acceptance as the standard treatment for patients with intestinal failure with life-threatening parenteral nutrition-related complications. We report our 4-year experience with intestinal and multivisceral transplantation. We performed 20 isolated small bowel and seven multivisceral ones, including three with liver. The underlying diseases were mainly short bowel syndrome due to intestinal infarction, chronic intestinal pseudo-obstruction, and Gardner syndrome. Indications for transplant were loss of central venous access in 14 patients, recurrent sepsis in eight patients, and major electrolyte and fluid imbalance in five patients. One-year patient actuarial survival rate was 94% for isolated intestinal transplants and 42% for multivisceral recipients (P =.003), while 1-year graft actuarial survival rate was 88.4% for isolated small bowel patients and 42.8% for multivisceral ones (P =.01). The death rate was 18.5%. Our graftectomy rate was 14.8%. Our immunosuppressive protocols were based on induction agents such as alemtuzumab, daclizumab, and antithymocyte globulins. The majority of our complications were bacterial infections, followed by rejections and relaparotomies; most rejection episodes were treated with steroid boluses and tapering. We believe that our results were due to optimal candidate and donor selection, short ischemia time, and use of induction therapy. Multivisceral transplantation is a more complex procedure with less frequent clinical indications than isolated small bowel transplant, but our data concerning multivisceral transplants include only a small number of patients and require further evaluation.

2005 - Un caso di tubercolosi post-trapianto ortotopico di fegato: limiti dell’impiego del quantiferon-TB gold nella diagnosi della infezione tubercolare latente ed attiva [Abstract in Rivista]
Codeluppi, M.; Cocchi, S.; Guaraldi, Giovanni; DI BENEDETTO, Fabrizio; Meacci, M.; Mecugni, B.; Esposito, Roberto; Gerunda, Giorgio Enrico
abstract

Il QuantiFERON-TB Gold è entrato recentemente in uso per la diagnosi dell'infezione tubercolare latente. Essi rileva la risposta di g interferon a due diversi antigeni tubercolari (ESAT6 e CFO10). La sua efficacia è sata considerata almeno paragonabile a quella del test cutaneo, ma nella diagnosi di infezione latente ed attiva in condizioni di immunodepressione non è mai stata estesamente studiata.

2005 - Use of prosthetic mesh in difficult abdominal waal closure after small bowel transplantation in adults. [Articolo su rivista]
DI BENEDETTO, Fabrizio; Lauro, A; Masetti, Michele; Cautero, Nicola; De, RUVO N; Quintini, Cristiano; DIAGO USO', Teresa; Romano, Antonio; Dazzi, Alessandro; Ramacciato, G; Cipriani, R; Ercolani, G; Grazi, Gl; Gerunda, Giorgio Enrico; Pinna, Antonio Daniele
abstract

Abdominal wall closure after intestinal transplantation in adult patients can be a difficult procedure. The main possibility offered by international experience is the use of myocutaneous flaps and abdominal wall transplantation. We report our experience in intestinal/multivisceral transplantation, including four difficult cases among 27 adult transplant recipients. Three patients underwent prosthetic mesh alone and one, a myocutaneous flap for abdominal closure after primary mesh positioning. We selected a mesh with a structure that allowed us to close the abdomen without creating adhesions and, at the same time, stimulating tissue repair. Two patients experienced local mesh infection, which has been kept under clinical control by antibiotics and daily medications till neoabdominal wall formation. The mesh was then removed. Another patient underwent mesh substitution for a suspicious fever. The last patient had mesh as a bridge for a subsequent myocutaneous flap from the thigh. All patients are in good health with well-functioning grafts and no need for parenteral nutrition. No enterocutaneous fistulae were detected.

2004 - Hepatic allograft salvage with early Doppler ultrasound diagnosis of acute vena cava thrombosis [Articolo su rivista]
Bertani, H; Pinna, Ad; DI BENEDETTO, Fabrizio; Quintini, Cristiano; Miller, C; Villa, Erica
abstract

Postoperative inferior vena cava obstruction is an uncommon complication after liver transplantation. Outflow obstruction, if not rapidly corrected, can lead to graft failure and the patient's death. We report a case in which Doppler ultrasound showed the thrombus inside the vessel, excluding extrahepatic causes of venous outflow obstruction, and permitted early surgical correction of the complication without graft loss.

2004 - Increased prothrombin time and platelet counts in living donor right hepatectomy: Implications for epidural anesthesia [Articolo su rivista]
A., Siniscalchi; Begliomini, Bruno; L., De Pietri; V., Braglia; M., Gazzi; Masetti, Michele; DI BENEDETTO, Fabrizio; Ad, Pinna; Cm, Miller; Pasetto, Alberto
abstract

The risks and benefits of adult-to-adult living donor liver transplantation need to be carefully evaluated. Anesthetic management includes postoperative epidural pain relief, however, even patients with a normal preoperative coagulation profile may suffer transient postoperative coagulation derangement. This study explores the possible causes of postoperative coagulation derangement after donor hepatectomy and the possible implications on epidural analgesia. Thirty donors, American Society of Anesthesiology 1, with no history of liver disease were considered suitable for the study. A thoracic epidural catheter was inserted before induction and removed when laboratory values were as follows: prothrombin time (PT) > 60%, activated partial thromboplastin time < 1.24 (sec), and platelet count > 100,000 mmfpound (mm'). Standard blood tests were evaluated before surgery, on admission to the recovery room, and daily until postoperative day (POD) 5. The volumes of blood loss and of intraoperative fluids administered were recorded. Coagulation abnormalities observed immediately after surgery may be related mostly to blood loss and to the diluting effect of the intraoperative infused fluids, although the extent of the resection appears to be the most important factor in the extension of the PT observed from POD 1. In conclusion, significant alterations in PT and platelet values were observed in our patients who underwent uncomplicated major liver resection for living donor liver transplantation. Because the potential benefits of epidural analgesia for liver resection are undefined according to available data, additional prospective randomized studies comparing the effectiveness and safety of intravenous versus epidural analgesia in this patient population should be performed.

2004 - Intermittent inflow occlusion in living liver donors: Impact on safety and remnant fuction [Articolo su rivista]
Miller, C; Masetti, Michele; Cautero, Nicola; DI BENEDETTO, Fabrizio; Lauro, A.; Romano, A.; Quintini, C.; Siniscalchi, A.; Begliomini, Bruno; Pinna, Ad
abstract

Clamping of the portal triad accomplishes complete inflow occlusion. This maneuver is commonly used during liver surgery to minimize blood loss but is not widely used in living donors undergoing resection for liver transplantation. We compared outcomes in living donors who underwent resection with and without inflow occlusion. We reviewed data on 2 nonsimultaneous living liver donor cohorts. The first 20 donors (group 1) underwent resection without inflow occlusion. In the next 15 donors (group 2), inflow occlusion was used during parenchymal transection, using cycles of 10–15 minutes occlusion and 6 minutes reperfusion. In donors, we recorded type of resection; ischemia times; blood loss; transfusions; peak ALT, AST, bilirubin, and INR in the first 5 days; hospital length of stay (LOS), and major complications. In recipients, we recorded peak ALT. In group 1, 19 of 20 donors underwent right hepatectomy. In group 2, 8 donors underwent right hepatectomy, and 7 donors had left lobectomies. Total ischemic time ranged from 16–49 minutes (mean, 31 ! 9 minutes). In group 1, two donors received a total of 5 U of allogeneic blood. In group 2, no donor required transfusion. Mean peak ALT was significantly higher in group 1 (521 ! 336 U/L) than group 2 (322 ! 162 U/L; P " 0.03). Mean INR was significantly higher in group 1 (1.8 ! 0.2) vs. group 2 (1.5 ! 0.2; P " 0.001). There were 4 major complications in group 1 (incisional hernia, transient liver failure, biliary stricture, and biliary leak) and no major intraoperative or postoperative complications in group 2. Mean LOS was significantly longer in group 1 (7.9 ! 2.9 days) than group 2 (6.2 ! 1.1 days; P " 0.04). Mean peak ALT in recipients trended lower in group 2. In conclusion, inflow occlusion was associated with reduced blood loss and less ischemic injury to hepatic remnants in the donors and the grafts in the recipients. These benefits were associated with a diminished incidence of major complications and shorter LOS. Inflow occlusion should be an essential part of living donor hepatectomy. (Liver Transpl 2004;10:244 –247.)

2004 - Intestinal transplantation for chronic intestinal pseudo-obstruction in adult patients. [Articolo su rivista]
M., Masetti; DI BENEDETTO, Fabrizio; Cautero, Nicola; V., Stanghellini; R. D., Giorgio; A., Lauro; Begliomini, Bruno; A., Siniscalchi; L., Pironi; R., Cogliandro; A. D., Pinna
abstract

Intestinal transplantation (ITx) has become a life-saving procedure for patients with irreversible intestinal failure who can no longer be maintained on parenteral nutrition (PN). This report presents the results of our experience on ITx in patients suffering from chronic intestinal pseudo-obstruction (CIPO). Between December 30, 2000 and May 30, 2003 six adult patients affected by CIPO underwent primary ITx at our Center. Pre-transplant evaluation, indication for ITx and surgical technique are reported. On December 30 2003, the mean follow-up was 25.0 months. No peri-operative deaths occurred in the study population and five out of six patients are alive, with 1-year patient and graft survival of 83.3\% and 66.6\%. Although our series is limited by the number of patients, our experience suggests that ITx transplantation should be considered in adult patients suffering from CIPO and PN life-threatening complication.

2004 - Living donor liver transplantation with left liver graft [Articolo su rivista]
Masetti, Michele; A., Siniscalchi; L. D., Pietri; V., Braglia; DI BENEDETTO, Fabrizio; Cautero, Nicola; Begliomini, Bruno; A., Romano; C. M., Miller; G., Ramacciato; A. D., Pinna
abstract

Small-for-size syndrome in LDLT is associated with graft exposure to excessive portal perfusion. Prevention of graft overperfusion in LDLT can be achieved through intraoperative modulation of portal graft inflow. We report a successful LDLT utilising the left lobe with a GV/SLV of only 20%. A 43 year-old patient underwent to LDLT at our institution. During the anhepatic phase a porto-systemic shunt utilizing an interposition vein graft anastomosed between the right portal branch and the right hepatic vein was performed. After graft reperfusion splenectomy was also performed. Portal vein pressure, portal vein flow and hepatic artery flow were recorded. A decrease of portal vein pressure and flow was achieved, and the shunt was left in place. The recipient post-operative course was characterized by good graft function. Small-for-size syndrome by graft overperfusion can be successfully prevented by utilizing inflow modulation of the transplanted graft. This strategy can permit the use of left lobe in adult-to-adult living donor liver transplantation.

2004 - Outcome of isolated small bowel and pancreas transplants retrieved from multiorgan donor: the in vivo technique. [Articolo su rivista]
DI BENEDETTO, Fabrizio; Quintini, Cristiano; Lauro, A.; Masetti, Michele; Cautero, Nicola; De Ruvo, N.; Sassi, S.; Diago Uso, T.; Di Francesco, F.; Romano, A.; Dalla Valle, R.; Boggi, U.; Risaliti, A.; Ramacciato, G.; Pinna, A. D.
abstract

Even when considering the possibility of organ rejection and the complications of immunosuppression, the risks associated with total parenteral nutrition therapy are life-threatening. Therefore, for patients with end-stage bowel disease small bowel transplantation (SBTx) is the only therapeutic option. The preferred method to procure these organs is debated, especially when, graft retrieval is associated with concurrent abdominal organ procurement of the pancreas, which shares part of the vascular inflow and outflow with the small bowel. While many surgeons procure the graft using the en bloc method, dissecting tissue at the back table, our preference is to use an in vivo technique, which results in shorter cold ischemia times and less bleeding during reperfusion of the pancreas/small bowel as well as decreased ascites production during the postoperative period and less edema and capsular bleeding of the pancreatic grafts. This article presents an analysis of 19 multiorgan cadaveric procurements using the in vivo technique with a focus on the quality of pancreas/small bowel postreperfusion properties during the first 5 to 6 postoperative months.

2004 - [Prognostic factors and long term outcome after surgery for hilar cholangiocarcinoma. Univariate and multivariate analysis] [Articolo su rivista]
G., Ramacciato; DI BENEDETTO, Fabrizio; Cautero, Nicola; M., Masetti; P., Mercantini; N., Corigliano; G., Nigri; A., Lauro; G., Ercolani; M. D., Gaudio; N. D., Ruvo; A. D., Pinna
abstract

Aim of the study was to evaluate the surgical strategy for the treatment of the hilar cholangiocarcinoma, focusing on the clinicopathological factors influencing the outcome. Between January 2001 and December 2003 23 patients out of 33 underwent surgery for hilar cholangiocarcinoma. All patients underwent resection of the extrahepatic biliary duct. This was the only treatment in patients with Bismuth-Corlette type I cholangiocarcinoma, or in patients not suitable for hepatic resection. In the other cases, resection of extrahepatic bile duct was associated to right or left hepatectomy. The univariate and multivariate analysis evaluated multiple clinicopathological factors in order to assess long term survival. Major hepatic resection was carried out in 19 (82\%) patients. Hepatic resection extended to the segment 4 was performed in 5 patients. Also, left hepatectomy was carried out in 14 patients, while resection of the caudate lobe in 7 (30\%) patients. No hospital mortality was recorded, while the overall morbidity was 43\%. The 1 year survival rate was 63.2\%, and the median survival rate 19 months. Recurrencies showed up in 12 patients (52\%). Among the other factors, low level of albumin (p = 0.006), positive resection margins (p = 0.003) and T (p = 0.02) mostly affected the long term survival. Surgery is the gold standard for achieving curative treatment of hilar cholangiocarcinoma. The bile duct resection, along with hepatic resection, the best option to increase long term survival of these patients. The univariate and multivariate analysis showed that low albumin levels, positive resection margins and T are the most important factors influencing long term survival.

2004 - Self-assembled extracellular matrix protein networks by microcontact printing [Articolo su rivista]
N., Sgarbi; D., Pisignano; DI BENEDETTO, Fabrizio; G., Gigli; R., Cingolani; R., Rinaldi
abstract

Physiological patterns of the extracellular matrix protein, laminin-1, were obtained on glass substrates by physisorption-assisted microcontact printing. Besides the well-retained antigenicity confirmed by indirect immunofluorescence assays, we investigated the supramolecular organization of the proteins by atomic force microscopy. We found the characteristic protein self-assembling in polygonal networks with well-defined sub-100 nm quaternary structures of laminin. The formation of these physiological mesh-like protein matrices was obtained by means of one-step soft lithography without any preliminary functionalization of glass, which can be exploited for many possible applications for cell cultures and biomolecular devices.

2004 - Three-year experience in clinical intestinal transplantation. [Articolo su rivista]
M., Masetti; Cautero, Nicola; A., Lauro; DI BENEDETTO, Fabrizio; Begliomini, Bruno; A., Siniscalchi; L., Pironi; M., Miglioli; A., Bagni; A. D., Pinna
abstract

BACKGROUND: The purpose of this study was to evaluate the outcome of 19 patients who underwent intestinal transplantation (ITx) for intestinal failure. METHODS: The 19 patients who underwent primary ITx between December 2000 and May 2003 were prescribed three different immunosuppressive protocols that included daclizumab, alemtuzumab, and antithymocyte globulin induction, respectively. A mucosal surveillance protocol for early detection of rejection consisted of zoom video endoscopy and serial biopsies associated with orthogonal polarization spectral imaging. Retrospective review of the clinical records was performed to assess the impact of new modalities of immunosuppression and intestinal mucosal monitoring on patient outcomes. RESULTS: All patients were adults (mean age 35.8 years). Etiology of intestinal failure included chronic intestinal pseudo-obstruction (n = 6), intestinal angiomatosis (n = 1), Gardner syndrome (n = 2), intestinal infarction (n = 8), radiation enteritis (n = 1), and intestinal atresia (n = 1). All patients experienced complications from total parenteral nutrition (TPN). Thirteen patients (68.4\%) received isolated small bowel, whereas six (31.6\%) received multivisceral grafts with or without the liver. Thirteen of 19 patients experienced at least one episode of rejection (68.4\%). Most ACR episodes were treated with steroid boluses and resolved completely within 5 days. The overall 1-year patient survival was 82\%. All living patients are in good health with functioning grafts having been weaned off TPN after a mean of 23.7 days post-ITx. DISCUSSION: Advances in immunosuppressive therapy with early detection and prompt treatment of rejection episodes make ITx a valuable treatment option for patients with intestinal failure and TPN-related life-threatening complications.

2004 - Use of a branch patch with the cystic artery in living-related liver transplantation. [Articolo su rivista]
DI BENEDETTO, Fabrizio; A., Lauro; Masetti, Michele; Cautero, Nicola; Quintini, Cristiano; A., Dazzi; G., Ramacciato; A., Risaliti; C. M., Miller; A. D., Pinna
abstract

Technical aspects in living-related liver transplantation are still under debate: the main pitfall is the arterial reconstruction due to the small diameter and the discrepancy between stumps, with subsequential increased risk of arterial thrombosis. The gold standard is the microsurgical technique, that reports the lowest risk of thrombosis, but it is a time consuming procedure requiring a long training. Our method of choice reconstructing hepatic artery in right lobe is the use of the cystic artery as a branch patch with the recipient hepatic artery by loop magnification, saving time and with a low incidence of hepatic artery thrombosis.

2003 - Hepatic resections for hepatocellular carcinoma (HCC): Short and long-term results on 106 cirrhotic patients [Articolo su rivista]
G., Ramacciato; P., Mercantini; N., Corigliano; Cautero, Nicola; Masetti, Michele; DI BENEDETTO, Fabrizio; C., Quintini; G., Balducci; A., Siniscalchi; Begliomini, Bruno; V., Ziparo; A., Pinna
abstract

To evaluate the short and long term outcome of liver resections for hepatocellular carcinoma in cirrhotic patients. A retrospective analysis was performed on 106 consecutive cirrhotic patients with hepatocellular carcinoma resected between June 1974 and September 2002 at the Department of Surgery Pietro Valdoni - University of Rome La Sapienza and at the Liver and Multivisceral Transplant Unit of the University of Modena. Univariate and multivariate analyses were performed on several clinicopathological variables to analyze factors affecting the long-term outcome and intrahepatic recurrence. Overall mortality and morbidity were 10.7% and 26% respectively. These rates significantly decreased in the last years: from 1997 to 2002 no hospital mortality has been recorded. After a median follow-up of 19 months (interquartile range: 10-36), tumour recurrence appeared in 25 patients (23,5%). The 1-, 3-, and 5-year overall survival rates were 86,6%, 70,3%, and 60,6%, respectively. The 1-, 3-, and 5-year disease-free survival rates were 86,3%, 58,1%, and 40,7%. On univariate analysis, viral ethiology of cirrhosis (p=0.03), presence of multiple nodules (p=0.02) and vascular invasion (p=0.05) were found to be related to a worse long-term survival. At the multivariate analysis only the viral ethiology of cirrhosis and the presence of multiple nodules were confirmed as indipendent prognostic factors. Early results after hepatic resection for HCC can be improved by using a limited surgical approach. The viral ethiology of cirrhosis, the presence of multiple nodules and vascular invasion negatively affected recurrence rate and long-term survival.

2003 - Ischemia and hepatic reperfusion: is it possible to reduce hepatic alterations? [Articolo su rivista]
R., Lanteri; R., Greco; E., Licitra; DI BENEDETTO, Fabrizio; G. L., Destri; A. D., Cataldo
abstract

Our aim was to evaluate liver damage after ischemia and reperfusion, and at the same time test the effectiveness of some drugs in preventing these alterations. For this study, we utilized 50 rats divided into four groups: three underwent hepatic ischemia through occlusion of the portal vein and hepatic artery for 30 min, and one underwent a sham operation. In all groups, hepatic enzymes and bilirubine were tested at 2 h, 3 h, 4 h, 24 h, and 30 h. The drugs utilized were: L-arginine, donor of nitric oxide, and L-canavanine, inhibitor of nitric oxide synthase (NOS). Our data showed that the drugs tested could make an improvement in hepatic function after ischemia/reperfusion, preventing its damage. These preliminary results could suggest a clinical application in order to prolong ischemic period during liver transplantation or liver resection in cirrhotic patients.

2003 - [Living donor liver transplantation, adult to adult]. [Articolo su rivista]
A., Pinna; M., Masetti; C., Miller; A., Dazzi; B., Begliomini; A., Siniscalchi; N., Cautero; F. D., Benedetto; A., Lauro; Girardis, Massimo; Villa, Erica; G., Ramacciato
abstract

Since living donor liver transplantation (LDLT) can offer a viable response to the lack of transplantable cadaveric organs, our center instituted an LDLT program in 2001.The authors report their experience with the first 35 LDLT procedures successfully completed at the Liver and Multiorgan Transplant Center of the University of Modena between 9 May 2001 and 21 May 2003. The case series comprised 35 patients, 7 of which received a left-half liver and 1 a left lobe.The global survival rate was 77.2\% (27 out of 35 patients), with a mean follow-up period of 295 days; the survival rate at 1 year was 81\%. In 4 cases (11\%) retransplantation was performed. The donor demographics are described; all donors returned to their normal activities before transplantation, after a mean follow-up period of 373 days. No intraoperative complications were experienced by the donors, whereas during the postoperative period, 2 donors (5.7\%) developed major complications (1 biliary fistula on the cut surface, 1 stenosis of the main bile duct).Our study shows that LDLT can be safely completed in the donor, with good results achieved in the recipient as well. Underlying these results is the accurate pretransplant assessment that continued into the operation itself. Even more important was the demonstrated ability and experience of the surgical team to attain results in the donor which we believe are necessary for carrying forth a LDLT program.

2002 - Il trapianto di fegato da donatore vivente: esperienza dell’Universita’ di Modena e Reggio Emilia. [Relazione in Atti di Convegno]
DI BENEDETTO, Fabrizio; Masetti, M; Cautero, N; Gelmini, Roberta; DALLA VALLE, R.; Quintini, C; Sassi, S; Landolfo, G; Diago, T; Jovine, Elio; Pinna, A. . D.
abstract

Il trapianto di fegato da donatore vivente: esperienza dell’Universita’ di Modena e Reggio Emilia.

2002 - Intestinal/multivisceral transplantation: University of Modena experience [Articolo su rivista]
Masetti, Michele; Jovine, Elio; Begliomini, Bruno; Cautero, Nicola; DI BENEDETTO, Fabrizio; Gelmini, Roberta; Villa, Erica; A., Merighi; A., Bagni; L., Bezer; Ad, Pinna
abstract

N/A

2002 - La terapia chirurgica dell’HCC nel paziente anziano. [Relazione in Atti di Convegno]
Gelmini, Roberta; Cautero, N; DI BENEDETTO, Fabrizio; Masetti, M; Quintini, C; Sassi, S; Ferrone, R; Landolfo, G; Jovine, Elio; Pinna, Antonio Daniele
abstract

La terapia chirurgica dell’HCC nel paziente anziano.

2002 - Modified multivisceral transplantation without a liver graft for Gardner/Desmoid syndrome and chronic intestinal pseudo-obstruction [Articolo su rivista]
Jovine, Elio; Masetti, Michele; Cautero, Nicola; DI BENEDETTO, Fabrizio; Gelmini, Roberta; S., Sassi; C., Quintini; Andreotti, Alessia; Begliomini, Bruno; A., Siniscalchi; Ad, Pinna
abstract

Multivisceral transplant (MVTx) was first performed by Starzi et al in 1988.[1] The results of small bowel transplantation have improved in the past 5 years secondary to the development of new immunosuppressive regimens, to refinements of surgical techniques, as well as to a better candidate selection. [2] The indications for small bowel transplantation are intestinal failure due to congenital or acquired anatomical loss of the intestine, vascular disease, primary disorders of intestinal motility, such as chronic idiopathic pseudo-obstruction syndrome (CIPOS), and intestinal mucosal disease leading to malabsorption. To these typical indications we can add Gardner’s syndrome (familial multiple polyposis) and desmoid tumors. [3] Gardner’s syndrome can affect the whole gastrointestinal tract, often presenting with desmoid lesions at the root of the mesentery. In some patients isolated small bowel transplantation is not crucial to completely treat the disease. Gastric and esophageal manometry is often used to assess whether the patient needs an isolated small bowel transplant or a MVTx. Here we report two cases of modified MVTx without the liver for Gardner/Desmoid syndrome and for CIPOS.

2002 - Orthogonal polarization spectral imaging: A new tool in morphologic surveillance in intestinal transplant recipients [Articolo su rivista]
Cautero, Nicola; Gelmini, Roberta; Villa, Erica; A., Bagni; A., Merighi; Masetti, Michele; DI BENEDETTO, Fabrizio; F., Di Francesco; L., Bezer; Begliomini, Bruno; Jovine, Elio; Ad, Pinna
abstract

Intestinal transplantation (ITx) can be considered a lifesaving procedure in patients with intestinal failure. However, despite improvements in the surgical technique and in patient selection, as well as in immunosuppressive therapy, successful ITx requires an early diagnosis of graft rejection. Acute cellular rejection (ACR) remains the most common and serious complication in clinical ITx. In this scenario frequent endoscopic and histologic surveillance are mandatory to achieve an early diagnosis of rejection and to tailor an effective immunosuppressive regimen. We compared zoom video endoscope (ZVE)[1] and orthogonal polarization spectral (OPS) imaging as techniques to predict qualitative modifications of microscopic architecture and villi microcirculation for the diagnosis of acute cellular rejection in small bowel transplant patients.

2002 - Procurement technique for isolated small bowel, pancreas, and liver from multiorgan cadaveric donor [Relazione in Atti di Convegno]
Jovine, Elio; DI BENEDETTO, Fabrizio; Quintini, C; Masetti, M; Cautero, N; Gelmini, Roberta; Andreotti, A; Bezer, L; Sassi, S; Boggi, U; Filipponi, F; Pinna, Antonio Daniele
abstract

Intestinal transplants, including either isolated small bowel and multivisceral grafts, have become in the last decade a valuable and safe therapeutic option for patients with intestinal failure. The improvements in intestinal transplants result basically from a better patients selection, refined surgical techniques, and immunosuppressants.[1]The purpose of this article is to define the feasibility of isolated small bowel harvesting simultaneously with pancreas and liver procurement from cadaveric multiorgan donor.

2002 - Tecnica chirurgica per il prelievo isolato di intestino, pancreas e fegato dallo stesso donatore cadavere multiorgano. [Relazione in Atti di Convegno]
DI BENEDETTO, Fabrizio; Masetti, M.; Cautero, N; Gelmini, Roberta; DALLA VALLE, R.; Quintini, C; Sassi, S; Landolfo, G; DI FRANCESCO, F; Diago, T; Jovine, Elio; Pinna, Ad
abstract

Tecnica chirurgica per il prelievo isolato di intestino, pancreas e fegato dallo stesso donatore cadavere multiorgano.

2002 - Trapianto di intestino: esperienza dell’Università di Modena e Reggio Emilia [Relazione in Atti di Convegno]
Quintini, C; Masetti, M; DI BENEDETTO, Fabrizio; Cautero, N; Gelmini, Roberta; DALLA VALLE, R; Sassi, S; Landolfo, G; DI FRANCESCO, F; Diago, T; Jovine, Elio; Pinna, A. D.
abstract

Trapianto di intestino: esperienza dell’Università di Modena e Reggio Emilia

2002 - Trattamento chirurgico del carcinoma del pancreas nel paziente anziano. [Relazione in Atti di Convegno]
Quintini, C; Gelmini, Roberta; Landolfo, G; DI BENEDETTO, Fabrizio; Masetti, M; Cautero, N; DALLA VALLE, R; Sassi, S; DI FRANCESCO, F; Jovine, Elio; Pinna, A. D.
abstract

Trattamento chirurgico del carcinoma del pancreas nel paziente anziano.

2001 - Factors involved in the functional recovery of a liver graft with particular emphasis on liver steatosis: a multivariate analysis. [Articolo su rivista]
L. D., Carlis; A., Giacomoni; A. O., Slim; V., Pirotta; DI BENEDETTO, Fabrizio; F., Manoochehri; A., Lauterio; C., Sammartino; G. F., Rondinara; D., Forti
abstract

No abstract available.

2001 - Liver transplantation for ecstasy-induced fulminant hepatic failure [Articolo su rivista]
L. D., Carlis; A. D., Gasperi; A. O., Slim; A., Giacomoni; A., Corti; E., Mazza; DI BENEDETTO, Fabrizio; A., Lauterio; K., Arcieri; G., Maione; G. F., Rondinara; D., Forti
abstract

No abstract available.

2001 - Modified multivisceral transplantation without liver for Gardner desmoid syndrome and cronic intestinal pseudoobstruction [Relazione in Atti di Convegno]
Jovine, Elio; Masetti, M; Cautero, N; DI BENEDETTO, Fabrizio; Gelmini, Roberta; Sassi, S; Quintini, C; Andreotti, A; Begliomini, Bruno; Siniscalchi, A; Pinna, Antonio Daniele
abstract

Modified multivisceral transplantation without liver for Gardner desmoid syndrome and cronic intestinal pseudoobstruction

2001 - Orthogonal Polarization Spectral (OPS) Imaging: A New Tool in Morphologic Surveillance in Intestinal Transplant Recipients [Relazione in Atti di Convegno]
N., Cautero; Gelmini, Roberta; Villa, Erica; A., Bagni; A., Merighi; M., Masetti; DI BENEDETTO, Fabrizio; F., DI FRANCESCO; L., Bezer; Begliomini, Bruno; Jovine, Elio; Pinna, Antonio Daniele
abstract

Orthogonal Polarization Spectral (OPS) Imaging: A New Tool in Morphologic Surveillance in Intestinal Transplant Recipients

2001 - Posttransplant lymphoproliferative disorders: report from a single center. [Articolo su rivista]
L. D., Carlis; A. O., Slim; A. D., Gasperi; G., Muti; A., Giacomoni; DI BENEDETTO, Fabrizio; A., Lauterio; V., Pirotta; A., Corti; E., Mazza; G. F., Rondinara; D., Forti
abstract

No abstract available.

2001 - Sirolimus-Tacrolimus combined immunosuppression and early steroidal withdrawal in liver transplantation. [Relazione in Atti di Convegno]
Pinna, Antonio Daniele; Jovine, Elio; Masetti, M; Gelmini, Roberta; Cautero, N; DI BENEDETTO, F; Bezer, L.
abstract

Sirolimus-Tacrolimus combined immunosuppression and early steroidal withdrawal in liver transplantation.

1999 - Serum lipid changes in liver transplantation: effect of steroids withdrawn in a prospective randomized trial under cyclosporine A therapy. [Articolo su rivista]
L. D., Carlis; L. S., Belli; G., Colella; G. F., Rondinara; A. O., Slim; A., Alberti; P., Aseni; C. V., Sansalone; V., Pirotta; DI BENEDETTO, Fabrizio; D., Forti
abstract

No abstract available.

1998 - Early pancreas retransplantation for vascular thrombosis in simultaneous pancreas-kidney transplants [Relazione in Atti di Convegno]
C. V., Sansalone; P., Aseni; M. L., Follini; O., Rossetti; A. O., Slim; G., Colella; DI BENEDETTO, Fabrizio; G., Rombolà; G. F., Rondinara; L. D., Carlis; C., Brunati; A., Meroni; R., Confalonieri; G., Civati; D., Forti
abstract

No abstract available.

1998 - Enteric versus bladder drainage in pancreas transplantation: initial experience at Niguarda Hospital, Milan. [Articolo su rivista]
C. V., Sansalone; P., Aseni; M. L., Follini; A. O., Slim; O., Rossetti; G., Colella; DI BENEDETTO, Fabrizio; G. F., Rondinara; L. D., Carlis; C., Brunati; A., Meroni; G., Rombolà; G., Civati; D., Forti
abstract

No abstract available.

1998 - Hepatocellular carcinoma: comparison between liver transplantation, resective surgery, ethanol injection, and chemoembolization. [Articolo su rivista]
G., Colella; R., Bottelli; L. D., Carlis; C. V., Sansalone; G. F., Rondinara; A., Alberti; L. S., Belli; F., Gelosa; G. M., Iamoni; A., Rampoldi; A. D., Gasperi; A., Corti; E., Mazza; P., Aseni; A., Meroni; A. O., Slim; M., Finzi; DI BENEDETTO, Fabrizio; F., Manochehri; M. L., Follini; G., Ideo; D., Forti
abstract

Between January 1989 and June 1997, 533 patients (423 male, 110 female, mean age 61 years, range 22-89 years) with hepatocellular carcinoma (HCC) were observed at our center. We report on 419 patients retrospectively compared for different treatments: liver transplantation (LT; 55 patients), resective surgery (RS; 41 patients), transarterial chemoembolization (TACE; 171 patients) and percutaneous ethanol injection (PEI; 152 patients). The 3- and 5-year actuarial survival rates were, respectively, 72\% and 68\% for LT, 64 and 44\% for RS, 54 and 36\% for PEI, and 32 and 22\% for TACE. Survival curves were compared for sex, age, tumor characteristics, alphafetoprotein level, Child class, and etiology of cirrhosis. All patient-related characteristics examined (sex, age) are not significantly related to patient survival. Tumor-related variables and associated liver disease variables significantly conditioned survival in relation to different treatments. LT seems to be the treatment of choice for monofocal HCC less then 5 cm in diameter and in selected cases of plurifocal HCC.

1997 - [Morpho-functional evaluation of subjects who had undergone surgery for ano-rectal malformations using the Peña technique] [Articolo su rivista]
S., Cacciaguerra; A., Papale; F., Lentini; DI BENEDETTO, Fabrizio; S., Gresta; A., Racalbuto; A. D., Benedetto
abstract

The approach to patients with Ano-Rectal Malformations (ARM) has undergone a substantial change in these last years due to the evolution of the studies of the anatomy and physiology carried out by Peña and de Vries. The authors report their experience on 15 patients and analyse the clinical and instrumental results according to the quality of life of the patients. There are different clinical criteria for the postoperative evaluation of these patients. The authors considered the Kelly, Kiesewetter, Peña and Holdschneider methods and compared the different values obtained. Moreover, they analysed the results of anorectal manometry performed in 10 patients and their correlations with clinical scores. The authors assert that the TC or NMR tests are unnecessary for these patients, since these methods demonstrate a correct position of the rectum within the muscular structure, but do not allow a correct evaluation of the quality of life of these patients. The clinical results obtained by the authors are satisfying; however, the number of patients is limited and the follow-up is relatively short.

1996 - Obstructive jaundice caused by lymph node compression in a child. [Articolo su rivista]
S., Cacciaguerra; P., Barone; G. I., Villa Trujillo; DI BENEDETTO, Fabrizio; G., Bartoloni; P., Milone; G., Petrillo; A. D., Benedetto
abstract

No abstract available.