GIORGIO ENRICO GERUNDA - personale UniMoRe

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GIORGIO ENRICO GERUNDA

COLLABORATORE DI RICERCA
Dipartimento di Scienze Biomediche, Metaboliche e Neuroscienze sede Policlinico

Pubblicazioni

2016 - Neoangiogenesis-related genes are hallmarks of fast-growing hepatocellular carcinomas and worst survival. Results from a prospective study [Articolo su rivista]
Villa, Erica; Critelli, Rosina Maria; Lei, Barbara; Marzocchi, Guido; Cammà, Calogero; Giannelli, Gianluigi; Pontisso, Patrizia; Cabibbo, Giuseppe; Enea, Marco; Colopi, Stefano; Caporali, Cristian; Pollicino, Teresa; Milosa, Fabiola; Karampatou, Aimilia; Todesca, Paola; Bertolini, Elena; Maccio, Livia; Martinez Chantar, Maria Luz; Turola, Elena; Del Buono, Mariagrazia; De Maria, Nicola; Ballestri, Stefano; Schepis, Filippo; Loria, Paola; Gerunda, Giorgio Enrico; Losi, Luisa; Cillo, Umberto
abstract

Objective: The biological heterogeneity of hepatocellular carcinoma (HCC) makes prognosis difficult. We translate the results of a genome-wide highthroughput analysis into a tool that accurately predicts at presentation tumour growth and survival of patients with HCC. Design: Ultrasound surveillance identified HCC in 78 (training set) and 54 (validation set) consecutive patients with cirrhosis. Patients underwent two CT scans 6 weeks apart (no treatment in-between) to determine tumour volumes (V0 and V1) and calculate HCC doubling time. Baseline-paired HCC and surrounding tissue biopsies for microarray study (Agilent Whole Human Genome Oligo Microarrays) were also obtained. Predictors of survival were assessed by multivariate Cox model. Results: Calculated tumour doubling times ranged from 30 to 621 days (mean, 107±91 days; median, 83 days) and were divided into quartiles: ≤53 days (n=19), 54-82 days (n=20), 83-110 days (n=20) and ≥111 days (n=19). Median survival according to doubling time was significantly lower for the first quartile versus the others (11 vs 41 months, 42, and 47 months, respectively) (p<0.0001). A five-gene transcriptomic hepatic signature including angiopoietin-2(ANGPT2), delta-like ligand 4(DLL4), neuropilin (NRP)/tolloid (TLL)-like 2(NETO2), endothelial cell-specific molecule-1(ESM1), and nuclear receptor subfamily 4, group A, member 1 (NR4A1) was found to accurately identify rapidly growing HCCs of the first quartile (ROC AUC: 0.961; 95% CI 0.919 to 1.000; p<0.0001) and to be an independent factor for mortality (HR: 3.987; 95% CI 1.941 to 8.193, p<0.0001). Conclusions: The hepatic five-gene signature was able to predict HCC growth in individual patient and the consequent risk of death. This implies a role of this molecular tool in the future therapeutic management of patients with HCC. Trial registration number ClinicalTrials.gov Identifier: NCT01657695.

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.

2015 - A new prognostic model to predict dropout from the waiting list in cirrhotic candidates for liver transplantation with MELD score <18. [Articolo su rivista]
Biselli, M; Dall'Agata, M; Gramenzi, A; Gitto, S; Liberati, C; Brodosi, L; Ravaioli, M; Gambato, M; Montalti, R; Pinna, Antonio Daniele; Burra, P; Gerunda, Giorgio Enrico; Cillo, U; Andreone, P; Bernardi, Mauro
abstract

BACKGROUND & AIMS: The model for end-stage liver disease (MELD) is used for organ allocation in liver transplantation (LT), but its prognostic performance is less accurate in patients with low score. We assess the outcome of patients with MELD < 18 awaiting LT, finding prognostic variables to identify a high dropout risk. METHODS: Training set consisted of 277 patients and validation cohort of 292 patients. Competing risk regression analysis, taking into account LT, was used for univariate/multivariate analysis. RESULTS: Ascites, sodium, bilirubin, albumin and glomerular filtration rate were independently associated with a 12-month dropout risk in the training set. Combining these five prognostic parameters, we calculated a new score named liver-renal-risk (LIRER). In the validation set, the 12-month LIRER concordance index showed a discrimination power [0.798, 95% confidence interval (95% CI) 0.793-0.803] better than MELD (0.582, 95% CI 0.575-0.588), Child-Turcotte-Pugh (0.687, 95% CI 0.681-0.693), MELD-sodium (0.721, 95% CI 0.715-0.727) and MELD-ascites-sodium (0.729, 95% CI 0.724-0.735), with a remarkable calibration (Hosmer-Lemeshow test: P = 0.91; R(2) = 0.911). Considering all study patients, the risk of wait list dropout increased with the rise in LIRER. The survival benefit analysis comparing the wait list dropout risk with the mortality of the 216 transplanted patients with same LIRER showed an important benefit for LT in patients with LIRER > 15.9. CONCLUSIONS: In patients with low MELD (<18), combination of ascites, sodium, albumin, bilirubin and renal function in a new score (LIRER) discriminates patients at high risk of medium-term adverse outcome from those in whom LT may be safely deferred.

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.

2014 - A Bayesian methodology to improve prediction of early graft loss after liver transplantation derived from the liver match study. [Articolo su rivista]
Angelico, M; Nardi, Antonella; Romagnoli, Renato; Marianelli, T; Corradini, Sg; Tandoi, F; Gavrila, C; Salizzoni, M; Pinna, Antonio Daniele; Cillo, U; Gridelli, B; De Carlis, Lg; Colledan, M; Gerunda, Giorgio Enrico; Costa, An; Strazzabosco, M; Liver, Match Study Investigators
abstract

BACKGROUND: To generate a robust predictive model of Early (3 months) Graft Loss after liver transplantation, we used a Bayesian approach to combine evidence from a prospective European cohort (Liver-Match) and the United Network for Organ Sharing registry. METHODS: Liver-Match included 1480 consecutive primary liver transplants performed from 2007 to 2009 and the United Network for Organ Sharing a time-matched series of 9740 transplants. There were 173 and 706 Early Graft Loss, respectively. Multivariate analysis identified as significant predictors of Early Graft Loss: donor age, donation after cardiac death, cold ischaemia time, donor body mass index and height, recipient creatinine, bilirubin, disease aetiology, prior upper abdominal surgery and portal thrombosis. RESULTS: A Bayesian Cox model was fitted to Liver-Match data using the United Network for Organ Sharing findings as prior information, allowing to generate an Early Graft Loss-Donor Risk Index and an Early Graft Loss-Recipient Risk Index. A Donor-Recipient Allocation Model, obtained by adding Early Graft Loss-Donor Risk Index to Early Graft Loss-Recipient Risk Index, was then validated in a distinct United Network for Organ Sharing (year 2010) cohort including 2964 transplants. Donor-Recipient Allocation Model updating using the independent Turin Transplant Centre dataset, allowed to predict Early Graft Loss with good accuracy (c-statistic: 0.76). CONCLUSION: Donor-Recipient Allocation Model allows a reliable donor and recipient-based Early Graft Loss prediction. The Bayesian approach permits to adapt the original Donor-Recipient Allocation Model by incorporating evidence from other cohorts, resulting in significantly improved predictive capability.

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<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 - 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 - SENTINEL NODE IN DIFFERENTIATED THYROID CANCER: COMPARISON BETWEEN VITAL-DYE PATENT BLUE, LYMPHOSCINTIGRAPHY AND COMBINED TECHNIQUE [Abstract in Atti di Convegno]
Gelmini, Roberta; Esposito, Sofia; Beghelli, Davide; Gerunda, Giorgio Enrico
abstract

Obiettivo dello studio : aim of the study is to evaluate the role of sentinel node (SN) identification in the treatment of differentiated thyroid cancer (DTC). We also aim to assess feasibility and reproducibility of the SN techniques with vital-dye patent blue, radiotracer and combined technique Materiali e metodi : the study is multicentric, prospective, randomized three arms open. We expect to enroll 120 patients in 2 years. Patients have to be preoperative diagnosis of DTC. Exclusion criteria are previous cervical surgery, medullary cancer, nodes metastasis and multifocal tumor. All patients undergo total thyroidectomy, SN identification and central compartment (CC) dissection: in Arm A SN identification is obtained with vital-dye Patent blue technique, in Arm B with lymphoscintigraphy and in Arm C with combined technique. Specimen histopathology provides information about the characteristics of primary tumor, SN and the remaining nodes with specific immuno-histochemistry protocols Principali risultati : so far we enrolled 42 patients Arm A (26 pts): 18 patients (69.2%) had negative SN and nonSN; 1 (3.8%) with negative SN had micrometastasis in 2 nodes of CC; 2 (7.6%) with macrometastasis in the SN had metastatic nodes in the CC and 1 (3.8%) had macrometastasis in the SN with no other positive nodes. In 4 (15.2%) patients identification of the SN wasn't possible and there was no evidence of metastasis in all nodes removed Arm B: 2 patients (100%) had negative SN and nonSN Arm C (14 pts): 4 patients (28.6%) had negative SN and nonSN; 1 (7.1%) with negative SN had macrometastasis in 2 nodes; 4 (28.6%) with macrometastasis in the SN had metastatic nodes in the CC and 1 (7.1%) had macrometastasis in the SN with no other positive nodes. In 4 (28.6%) patients identification of the SN wasn't possible and in 3 of them there was no evidence of metastasis Conclusioni : so far the data we gathered are too few to make statistic significant conclusions. Once adequate scientific evidence is available, detection of the SN could become a routine procedure in DTC treatment, avoiding central compartment dissection in patients with negative SN. The achievement of a standard protocol of SN detection remains an important issue to solve, although both techniques had shown a good rate of detection of the SN, several studies report that the combined method could reduce false negatives and increase detection rates of SN metastases

2013 - Effects of mycophenolate mofetil introduction in liver transplant patients: results from an observational, non-interventional, multicenter study (LOBSTER). [Articolo su rivista]
Schlitt, Hj; Jonas, S; Ganten, Tm; Grannas, G; Moench, C; Rauchfuss, F; Obed, A; Tisone, G; Pinna, Antonio Daniele; Gerunda, Giorgio Enrico; Beckebaum, S.
abstract

The benefits of calcineurin inhibitor (CNI)-sparing regimens on renal function following liver transplantation (LT) have been demonstrated in clinical studies. This observational study assessed the real-life effects of mycophenolate mofetil (MMF) introduction in LT patients. Four hundred and ninety-seven patients in whom MMF was introduced according to local standards or clinical considerations were entered. Patients were grouped by time between transplantation and start of MMF (start of study): Group A (n = 263): ≤6 d; Group B (n = 64): >6 d to ≤1 month; Group C (n = 74): >1 month to ≤1 yr; and Group D (n = 96): >1 yr. CNI sparing occurred in all groups, particularly in Groups C and D. Mean MMF doses at 12 months were 1202.7, 1363.5, 1504.7, and 1578.1 mg/d, respectively, in Groups A-D. At introduction of MMF, median glomerular filtration rate was 73.3, 81.7, 62.7, and 53.7 mL/min/1.73 m(2) in Groups A-D. At 12 months, this decreased to 66 mL/min/1.73 m(2) in Groups A and B, remained stable in Group C, and increased in Group D (64.8 mL/min/1.73 m(2) ). Serious adverse drug reactions were lowest in Group D. In conclusion, MMF with a subsequent decrease in CNI was well tolerated and improved renal function even years after transplantation. A more forceful MMF dosing strategy with greater CNI sparing may further improve renal function.

2013 - Hepatitis B-core antibody positive donors in liver transplantation and their impact on graft survival: evidence from the Liver Match cohort study. [Articolo su rivista]
Angelico, M; Nardi, Antonella; Marianelli, T; Caccamo, L; Romagnoli, Renato; Tisone, G; Pinna, Antonio Daniele; Avolio, Aw; Fagiuoli, S; Burra, P; Strazzabosco, M; Costa, An; Gerunda, Giorgio Enrico; Liver, Match Investigators
abstract

BACKGROUND & AIMS: The appropriate allocation of grafts from HBcAb positive donors in liver transplantation is crucial, yet a consensus is still lacking. METHODS: We evaluated this issue within Liver Match, a prospective observational Italian study. Data from 1437 consecutive, first transplants performed in 2007-2009 using grafts from deceased heart beating donors were analyzed (median follow-up: 1040 days). Of these, 219 (15.2%) were HBcAb positive. Sixty-six HBcAb positive grafts were allocated to HBsAg positive and 153 to HBsAg negative recipients. RESULTS: 329 graft losses occurred (22.9%): 66 (30.1%) among 219 recipients of HBcAb positive grafts, and 263 (21.6%) among 1218 recipients of HBcAb negative grafts. Graft survival was lower in recipients of HBcAb positive compared to HBcAb negative donors, with unadjusted 3-year graft survival of 0.69 (s.e. 0.032) and 0.77 (0.013), respectively (log-rank, p=0.0047). After stratifying for recipient HBsAg status, this difference was only observed among HBsAg negative recipients (log rank, p=0.0007), 3-year graft survival being excellent (0.88, s.e. 0.020) among HBsAg positive recipients, regardless of the HBcAb donor status (log rank, p=0.4478). Graft loss due to de novo HBV hepatitis occurred only in one patient. At Cox regression, hazard ratios for graft loss were: MELD (1.30 per 10 units, p=0.0002), donor HBcAb positivity (1.56, p=0.0015), recipient HBsAg positivity (0.43, p <0.0001), portal vein thrombosis (1.99, p=0.0156), and DRI (1.41 per unit, p=0.0325). CONCLUSIONS: HBcAb positive donor grafts have better outcomes when transplanted into HBsAg positive than HBsAg negative recipients. These findings suggest that donor HBcAb positivity requires more stringent allocation strategies.

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 - Renal function at two years in liver transplant patients receiving everolimus: results of a randomized, multicenter study [Articolo su rivista]
Saliba, F; De Simone, P; Nevens, F; De Carlis, L; Metselaar, Hj; Beckebaum, S; Jonas, S; Sudan, D; Fischer, L; Duvoux, C; Chavin, Kd; Koneru, B; Huang, Ma; Chapman, Wc; Foltys, D; Dong, G; Lopez, Pm; Fung, J; Junge, G; Gerunda, Giorgio Enrico; H2304, Study Group
abstract

Abstract In a 24-month prospective, randomized, multicenter, open-label study, de novo liver transplant patients were randomized at 30 days to everolimus (EVR) + Reduced tacrolimus (TAC; n = 245), TAC Control (n = 243) or TAC Elimination (n = 231). Randomization to TAC Elimination was stopped prematurely due to a significantly higher rate of treated biopsy-proven acute rejection (tBPAR). The incidence of the primary efficacy endpoint, composite efficacy failure rate of tBPAR, graft loss or death postrandomization was similar with EVR + Reduced TAC (10.3%) or TAC Control (12.5%) at month 24 (difference -2.2%, 97.5% confidence interval [CI] -8.8%, 4.4%). BPAR was less frequent in the EVR + Reduced TAC group (6.1% vs. 13.3% in TAC Control, p = 0.010). Adjusted change in estimated glomerular filtration rate (eGFR) from randomization to month 24 was superior with EVR + Reduced TAC versus TAC Control: difference 6.7 mL/min/1.73 m(2) (97.5% CI 1.9, 11.4 mL/min/1.73 m(2), p = 0.002). Among patients who remained on treatment, mean (SD) eGFR at month 24 was 77.6 (26.5) mL/min/1.73 m(2) in the EVR + Reduced TAC group and 66.1 (19.3) mL/min/1.73 m(2) in the TAC Control group (p < 0.001). Study medication was discontinued due to adverse events in 28.6% of EVR + Reduced TAC and 18.2% of TAC Control patients. Early introduction of everolimus with reduced-exposure tacrolimus at 1 month after liver transplantation provided a significant and clinically relevant benefit for renal function at 2 years posttransplant.

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 - Efficacy and safety of maribavir dosed at 100 mg orally twice daily for the prevention of cytomegalovirus disease in liver transplant recipients: a randomized, double-blind, multicenter controlled trial. [Articolo su rivista]
Winston, Dj; Saliba, F; Blumberg, E; Abouljoud, M; Garcia Diaz, Jb; Goss, Ja; Clough, L; Avery, R; Limaye, Ap; Ericzon, Bg; Navasa, M; Troisi, Ri; Chen, H; Villano, Sa; Uknis, Me; Gerunda, Giorgio Enrico; 1263 301, Clinical Study Group
abstract

Maribavir is an oral benzimidazole riboside with potent in vitro activity against cytomegalovirus (CMV), including some CMV strains resistant to ganciclovir. In a randomized, double-blind, multicenter trial, the efficacy and safety of prophylactic oral maribavir (100 mg twice daily) for prevention of CMV disease were compared with oral ganciclovir (1000 mg three times daily) in 303 CMV-seronegative liver transplant recipients with CMV-seropositive donors (147 maribavir; 156 ganciclovir). Patients received study drug for up to 14 weeks and were monitored for CMV infection by blood surveillance tests and also for the development of CMV disease. The primary endpoint was Endpoint Committee (EC)-confirmed CMV disease within 6 months of transplantation. In a modified intent-to-treat analysis, the noninferiority of maribavir compared to oral ganciclovir for prevention of CMV disease was not established (12% with maribavir vs. 8% with ganciclovir: event rate difference of 0.041; 95% CI: -0.038, 0.119). Furthermore, significantly fewer ganciclovir patients had EC-confirmed CMV disease or CMV infection by pp65 antigenemia or CMV DNA PCR compared to maribavir patients at both 100 days (20% vs. 60%; p < 0.0001) and at 6 months (53% vs. 72%; p = 0.0053) after transplantation. Graft rejection, patient survival, and non-CMV infections were similar for maribavir and ganciclovir patients. Maribavir was well-tolerated and associated with fewer hematological adverse events than oral ganciclovir. At a dose of 100 mg twice daily, maribavir is safe but not adequate for prevention of CMV disease in liver transplant recipients at high risk for CMV disease.

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 - 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

2012 - Surgical Approach for Long-term Survival of Patients With Intrahepatic Cholangiocarcinoma: A Multi-institutional Analysis of 434 Patients. [Articolo su rivista]
Ribero, D; Pinna, Antonio Daniele; Guglielmi, Andrea; Ponti, A; Nuzzo, G; Giulini, Sm; Aldrighetti, L; Calise, F; Gerunda, Giorgio Enrico; Tomatis, M; Amisano, M; Berloco, P; Torzilli, G; Capussotti, L; Italian, Intrahepatic Cholangiocarcinoma Study Group
abstract

OBJECTIVES To examine the outcomes of a hepatectomy for intrahepatic cholangiocarcinoma (IHC) and to clarify the prognostic impact of a lymphadenectomy and the surgical margin. Large series of patients who were surgically treated for IHC are scarce. Thus, prognostic factors and long-term survival after resection of IHC remain uncertain. DESIGN Prospective study of patients who were surgically treated for IHC. Clinicopathologic, operative, and long-term survival data were analyzed. SETTING Prospectively collected data of all consecutive patients with pathologically confirmed IHC who had undergone liver resection with a curative intent at 1 of 16 tertiary referral centers were entered into a multi-institutional registry. PATIENTS All consecutive patients who underwent a hepatectomy with a curative intent for IHC (1990-2008) were identified from a multi-institutional registry. RESULTS A total of 434 patients were included in the analysis. Most patients underwent a major or extended hepatectomy (70.0%) and a systematic lymphadenectomy (62.2%). The incidence of lymph node metastases (overall, 36.9%) increased with increased tumor size, with 24.4% of patients with a small IHC (diameter ≤3 cm) having N1 disease. Almost one-third of patients required an additional major procedure to obtain a R0 resection in 84.6% of the cases. In these patients, the median time of survival was 39 months, and the 5-year survival rate was 39.8%. Lymph node metastases (hazard ratio, 2.21; P < .001), multiple tumors (hazard ratio, 1.50; P = .009), and an elevated preoperative cancer antigen 19.9 level (hazard ratio, 1.62; P = .006) independently predicted an adverse prognosis. Conversely, survival was not influenced by the width of a negative resection margin (P = .61). The potential survival benefit of a lymphadenectomy was assessed with the therapeutic value index, which was calculated to be 5.9 points. CONCLUSIONS Survival rates after a hepatectomy with a curative intent for IHC at tertiary referral centers exceed the survival rates reported in most study series in single institutions, which strengthens the value of an aggressive approach to radical resection. Lymph node metastases and multiple tumors are associated with decreased survival rates, but they should not be considered selection criteria that prevent other patients from undergoing a potentially curative resection. Lymphadenectomy should be considered for all patients.

2012 - Treatment of hepatitis C recurrence is less successful in female than in male liver transplant recipients. [Articolo su rivista]
Giannelli, V; Giusto, M; Farcomeni, A; Ponziani, Fr; Pompili, M; Vigano', Raffaella; Iemmolo, Rm; Donato, Mf; Rendina, Marisa; Toniutto, P; Pasulo, L; Morelli, Mc; De Martin, E; Miglioresi, L; Di Paolo, D; Fagiuoli S, Merli M; Gerunda, Giorgio Enrico; Study, AISF RECOLT C. group .
abstract

It has been recently suggested that the risk of graft loss after liver transplantation (LT) may increase in female HCV patients. The aim of the study was to examine gender differences in HCV therapy tolerance and outcome in LT patients treated for HCV recurrence. A retrospective study was conducted on liver recipients with HCV recurrence, who were given antiviral therapy from 2001 to 2009 in 12 transplant centers in Italy. Sustained virological response (SVR), adherence-to-therapy, and side effects were evaluated. A multivariate logistic regression model was used after adjusting for possible confounders. The data regarding 342 treated patients were analyzed. SVR was reported in 38.8% of patients. At baseline, male and female did not differ in HCV viral load, histology, or rate of diabetes. SVR was lower in females than in males (29.5% vs. 42.1%; P=0.03). Adherence-to-therapy was also lower in females than in males 43.4% vs. 23.8%; P=0.001); anemia was the main reason for lower adherence. In a multivariate analysis in patients Genotype1, female gender (P<0.04), early virological response (P<0.0001), and adherence to therapy (P<0.0001) were independent predictors for SVR. In conclusion, female gender represents an independent negative prognostic factor for the outcome of HCV antiviral therapy after LT.

2011 - Balancing Donor and Recipient Risk Factors in Liver Transplantation: The Value of D‐MELD With Particular Reference to HCV Recipients [Articolo su rivista]
Avolioa, A. W.; Cillob, U.; Salizzoni, M.; De Carlis, L.; Colledan, M.; Gerunda, G. E.; Mazzaferro, V.; Tisone, G.; Romagnoli, R.; Caccamo, L.; Rossi, M.; Vitale, A.; Cucchetti, A.; Lupo, L.; Gruttadauria, S.; Nicolotti, N.; Burra, P.; Gasbarrini, A.; Agnes, S.; behalf of the Donor-to-Recipient Italian Liver Transplant (D2R-ILTx) Study Group, On
abstract

We read with interest the article of Braat et al. (1) The authors developed, using the Euro-Transplant database, a novel donor risk index (ET-DRI) in order to predict and stratify the outcome after liver transplantation. Like Feng and coauthors did for to the American DRI (2), the authors postulated that donor quality is the strongest determinant of recipient outcome. However, while DRI and ET-DRI are helpful in recognizing grafts with expected higher risk, both fail to provide information whether to accept or not a liver for a certain recipient. We feel that such a suggestion requires deeper investigation and discussion. The authors suggest that ET-DRI should be used in the allocation.1 Although several recipient parameters were tested (age, indication, MELD, urgency), established studies (3–7) on donor-to-recipient match (D2Rm) were not considered by the authors.1 The merits of the current MELD system are simplicity, objectivity and accuracy in predicting waiting list mortality, as well as equity, since disease severity is the only prioritizing factor. Disadvantages of the current system include a pressure toward poorer outcomes as the sickest (highest MELD) recipients often match with higher risk donors, resulting increased frequency of futile transplantations. Yet, the desire for a balance between utility and need in organ allocation has not been completely realized. Scientific efforts to improve utility by improving D2Rm (LYFT, life years from transplant) have been difficult to implement as allocation policy due to concerns about policy complexity and limiting of access for some recipient subgroups. Intending to decrease the frequency of unsustainable donor-to-recipient matches, D-MELD was developed to account for the two dominant variables in the prediction of outcome, patient condition at transplant, as measured by MELD score, and donor quality, as measured by age (3,4). Being the product of two continuous variables, donor age and MELD, D-MELD produces a continuous riskgradient predicting both increased postoperative mortality and length of stay. The original D-MELDmodel (3) has been further refined in the Italian study (4,5) analyzing the risk in combination with recipient age, primary indication, portal vein status, retransplant status and center volume. Similar to D-MELD a novel score, BAR (BAlance of Risk) score (6has been developed. Differently from the ET-DRI, the BAR score adds to donor age recipient age, MELD, retransplant status, need of mechanical ventilation and cold ischemia time (CIT). The strength of currently developed D2Rm scores (SOFT [7], D-MELD [3,4] and BAR [6]) lies in the improved predictive ability analyzing the combination between donor– recipient factors. Furthermore, D-MELD and BAR, developed from the UNOS database, have been validated in Europe demonstrating superiority to other scores which include only donor or recipient factors (DRI, MELD). Those score have therefore a great potential to be helpful in deciding which organs should not be transplanted to high-risk candidates. Therefore, ET-DRI should be compared to other D2Rm scores for both predictive accuracy and applicability across differing patient populations. However, scores should not determine or limit transplantation opportunities. Any proposal to improve utility in allocation should be vetted in open forum, fully recognizing the ethical, scientific and practical limitations

2011 - Combined liver-kidney transplantation in HIV infected patients [Abstract in Rivista]
Benedetto, F. Di; D'Amico, Giuseppe; Tarantino, Giuseppe; Ruvo, N. De; Cautero, Nicola; Montalti, R.; Guerrini, Gian Piero; Ballarin, Roberto; Spaggiari, Mario; Cocchi, Stefania; Baisi, B.; Cappelli, Gianni; 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 - 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

2011 - Comparison of the prognostic accuracy of the sixth and seventh editions of the TNM classification for intrahepatic cholangiocarcinoma. [Articolo su rivista]
Ribero, D; Nuzzo, G; Amisano, M; Tomatis, M; Guglielmi, Andrea; Giulini, Sm; Aldrighetti, L; Calise, F; Gerunda, Giorgio Enrico; Pinna, Antonio Daniele; Capussotti, L; Italian, Chapter of IHPBA
abstract

BACKGROUND: The seventh TNM edition introduced a new, specific staging structure for intrahepatic cholangiocarcinoma (IHC). OBJECTIVE: To compare the accuracy of the sixth and the new seventh edition to predict survival after hepatectomy for IHC. METHODS: In all, 434 consecutive patients who underwent hepatectomy at 16 tertiary-care centres (1990-2008) were identified. End points were overall (OS) and recurrence-free survival (RFS) for both T cohorts and stage strata. RESULTS: After a median follow-up of 32.4 months, 3- and 5-year OS and RFS estimates were 47.1% and 32.9%, and 26.5% and 19.1%, respectively. Overall, both the editions were statistically significant discriminators of OS and RFS (P < 0.05). However, the survival curves of the new T2a and T2b cohorts appear superimposed. Conversely, the old T2 and T3 cohorts accurately stratify patients into distinct prognostic groups (P < 0.01). The seventh edition does not show monotonicity of gradients (the T4 category demonstrates significantly better OS and RFS compared with T2 patients). The seventh edition stage I and II are significantly different whereas the old stage I and II were not. CONCLUSIONS: The new seventh edition of the AJCC/UICC Staging System proved to be adequate although further studies are need to confirm its superiority compared with the previous edition.

2011 - FOLFOX6 and bevacizumab in non-optimally resectable liver metastases from colorectal cancer [Articolo su rivista]
Bertolini, Federica; Malavasi, Norma; Scarabelli, Laura; Fiocchi, Federica; Bagni, Bruno; DEL GIOVANE, Cinzia; Colucci, G; Gerunda, Giorgio Enrico; Depenni, Roberta; Zironi, S; Fontana, A; Pettorelli, Elisa; Luppi, G; Conte, Pierfranco
abstract

BACKGROUND: In patients with colorectal liver metastases (CLM) R0 resection significantly improves overall survival (OS). METHODS: In this report, we present the results of a phase II trial of FOLFOX6+bevacizumab in patients with non-optimally resectable CLM. Patients received six cycles of FOLFOX6+ five of bevacizumab. Patients not achieving resectability received six additional cycles of each. A PET-CT was performed at baseline and again within 1 month after initiating treatment. RESULTS: From September 2005 to July 2009, 21 patients were enrolled (Male/Female: 15/6; median age: 65 years). An objective response (OR) was documented in 12 cases (57.1%; complete responses (CRs): 3, partial response (PR): 9); one patient died from toxicity before surgery. Thirteen patients underwent radical surgery (61.9%). Three (23%) had a pathological CR (pCR). Six patients (46.1%) experienced minor postsurgical complications. After a median 38.8-month follow-up, the median OS was 22.5 months. Patients achieving at least 1 unit reduction in Standard uptake value (SUV)max on PET-CT had longer progression-free survival (PFS) (median PFS: 22 vs 14 months, P=0.001). CONCLUSIONS: FOLFOX6+bevacizumab does not increase postsurgical complications, yields high rates of resectability and pCR. Early changes in PET-CT seem to be predictive of longer PFS.

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 - 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 Match, a prospective observational cohort study on liver transplantation in Italy: study design and current practice of donor-recipient matching. [Articolo su rivista]
Angelico, M; Cillo, U; Fagiuoli, S; Gasbarrini, A; Gavrila, C; Marianelli, T; Costa, An; Nardi, Antonella; Strazzabosco, M; Burra, P; Agnes, S; Baccarani, U; Calise, F; Colledan, M; Cuomo, O; De Carlis, L; Donataccio, M; Ettorre, Gm; Gerunda, Giorgio Enrico; Gridelli, B; Lupo, L; Mazzaferro, V; Pinna, Antonio Daniele; Risaliti, A; Salizzoni, M; Tisone, G; Valente, U; Rossi, G; Rossi, M; Zamboni, F; Liver, Match Investigators
abstract

BACKGROUND: The Liver Match is an observational cohort study that prospectively enrolled liver transplantations performed at 20 out of 21 Italian Transplant Centres between June 2007 and May 2009. Aim of the study is to investigate the impact of donor/recipient matching on outcomes. In this report we describe the study methodology and provide a cross-sectional description of donor and recipient characteristics and of graft allocation. METHODS: Adult primary transplants performed with deceased heart-beating donors were included. Relevant information on donors and recipients, organ procurement and allocation were prospectively entered in an ad hoc database within the National Transplant Centre web-based Network. Data were blindly analysed by an independent Biostatistical Board. RESULTS: The study enrolled 1530 donor/recipient matches. Median donor age was 56 years. Female donors (n = 681, median 58, range 12-92 years) were older than males (n = 849, median 53, range 2-97 years, p < 0.0001). Donors older than 60 years were 42.2%, including 4.2% octogenarians. Brain death was due to non-traumatic causes in 1126 (73.6%) cases. Half of the donor population was overweight, 10.1% was obese and 7.6% diabetic. Hepatitis B core antibody (HBcAb) was present in 245 (16.0%) donors. The median Donor Risk Index (DRI) was 1.57 (>1.7 in 35.8%). The median cold ischaemia time was 7.3h (≥ 10 in 10.6%). Median age of recipients was 54 years, and 77.7% were males. Hepatocellular carcinoma (HCC) was the most frequent indication overall (44.4%), being a coindication in roughly 1/3 of cases, followed by viral cirrhosis without HCC (28.2%) and alcoholic cirrhosis without HCC (10.2%). Hepatitis C virus infection (with or without HCC) was the most frequent etiologic factor (45.9% of the whole population and 71.4% of viral-related cirrhosis), yet hepatitis B virus infection accounted for 28.6% of viral-related cirrhosis, and HBcAb positivity was found in 49.7% of recipients. The median Model for End Stage Liver Disease (MELD) at transplant was 12 in patients with HCC and 18 in those without. Multivariate analysis showed a slight but significant inverse association between DRI and MELD at transplant. CONCLUSIONS: The deceased donor population in Italy has a high-risk profile compared to other countries, mainly due to older donor age. Almost half of the grafts are transplanted in recipients with HCC. Higher risk donors tend to be preferentially allocated to recipients with HCC, who are usually less ill and older. No other relevant allocation strategy is currently adopted at national level.

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 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 = .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 = .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 = .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 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 - 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 - 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 - 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 < 0.001). The incidence of CKD stage ≥3 (estimated glomerular fil- tration rate <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 - Evaluation of HIV positive recipients of orthotopic liver transplant (OLT): an observational study in the modena consultation liaison psychiatric service [Abstract in Rivista]
Borsari, Lucia; M., Ferrara; V., Barbanti Silva; Pingani, Luca; S., Cocchi; Guaraldi, Giovanni; Gerunda, Giorgio Enrico; Rigatelli, Marco; Ferrari, Silvia
abstract

18th European Congress of Psychiatry

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 - 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 - 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 >or=50 years (P = .046); donor body mass index (BMI) > 27 (P = .016); genotype 1 versus 2 to 3 (P = 0.010), aspartate transferase (AST) before therapy >or= 140 U/L (P = .046), alanine transferase before therapy >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 - [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.

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 - 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) > 1.8 mg/dL and estimated glomerular filtration rates (eGFR) < 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 - Performance of tests for latent tuberculosis in different groups of immunocompromised patients. [Articolo su rivista]
Richeldi, Luca; Losi, M; D'Amico, Roberto; Luppi, M; Ferrari, A; Mussini, Cristina; Codeluppi, M; Cocchi, S; Prati, F; Paci, V; Meacci, M; Meccugni, B; Rumpianesi, F; Roversi, P; Cerri, Stefania; Luppi, F; Ferrara, G; Latorre, I; Gerunda, Giorgio Enrico; Torelli, G; Esposito, R; Fabbri, Leonardo
abstract

BACKGROUND: Immunocompromised persons infected with Mycobacterium tuberculosis (MTB) have increased risk of tuberculosis (TB) reactivation, but their managementis hampered by the occurrence of false-negative results of the tuberculin skin test (TST). The T-cell interferon (IFN)-gamma release blood assays T-SPOT.TB(TS.TB) [Oxford Immunotec; Abingdon, UK] and QuantiFERON-TB Gold In-Tube (QFT-IT) [Cellestis Ltd; Carnegie, VIC, Australia] might improve diagnostic accuracy forlatent TB infection (LTBI) in high-risk persons, although their performance in different groups of immunocompromised patients is largely unknown.METHODS AND RESULTS: Over a 1-year period, we prospectively enrolled patients in three different immunosuppressed groups, as follows: 120 liver transplantation candidates (LTCs); 116 chronically HIV-infected persons; and 95 patients with hematologic malignancies (HMs). TST, TS.TB, and QFT-IT were simultaneouslyperformed, their results were compared, and intertest agreement was evaluated.Overall, TST provided fewer positive results (10.9%) than TS.TB (18.4%; p <0.001) and QFT-IT (15.1%; p = 0.033). Significantly fewer HIV-infected individuals had at least one positive test (9.5%) compared with LTCs (35.8%; p < 0.001) and patients with HMs (29.5%; p < 0.001). Diagnostic agreement between tests was moderate (kappa = 0.40 to 0.65) and decreased in the HIV-infected group when the results of the TS.TB were compared with either TST (kappa = 0.16) orQFT-IT (kappa = 0.19). Indeterminate blood test results due to low positive control values were significantly more frequent with QFT-IT (7.2%) than with TS.TB (0.6%; p < 0.001).CONCLUSIONS: Blood tests identified significantly more patients as being infected with MTB than TST, although diagnostic agreement varied across groups. Based onthese results, we recommend tailoring application of the new blood IFN-gamma assays for LTBI in different high-risk groups and advise caution in their current use in immunosuppressed patients.

2009 - Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis [Articolo su rivista]
Mazzaferro, V; Llovet, Jm; Miceli, R; Bhoori, S; Schiavo, M; Mariani, Maria Luisa; Camerini, T; Roayaie, S; Schwartz, Me; Grazi, Gl; Adam, R; Neuhaus, P; Salizzoni, M; Bruix, J; Forner, A; De Carlis, L; Cillo, U; Burroughs, Ak; Troisi, R; Rossi, Massimo; Gerunda, Giorgio Enrico; Lerut, J; Belghiti, J; Boin, I; Gugenheim, J; Rochling, F; Van Hoek, B; Majno, P; Metroticket, Investigator Study Group
abstract

Abstract In nine patients with posttransplant Kaposi sarcoma (KS) T-cell responses to human herpesvirus (HHV)-8 latent and lytic antigens, as detected by enzyme-linked-immunospot (Elispot) assay, were absent at disease onset. Virus-specific T-cell responses were detected in six renal recipients at remission after a reduction of calcineurin inhibitors (CIs), and in two HHV-8 seropositive renal recipients without KS. In two liver recipients undergoing switch from CIs to sirolimus (SRL), normalization of the T-cell repertoire and recovery of both HHV-8-specific effector and memory T lymphocytes were associated with complete KS remission. In a renal recipient undergoing SRL conversion, the early recovery of HHV-8-specific effector but not of memory T lymphocytes, was associated only with partial remission. Neither rejection nor changes in graft function were observed after SRL conversion. HHV-8-specific T-cell responses are required to achieve posttransplant KS remission, and may be restored under SRL, while maintaining effective immunosuppression.

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 (>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 - 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 - Changes in the immune responses against human herpesvirus-8 in the disease course of posttransplant Kaposi sarcoma [Articolo su rivista]
Barozzi, Patrizia; Bonini, C; Potenza, Leonardo; Masetti, Michele; Cappelli, Gianni; Gruarin, P; Whitby, D; Gerunda, Giorgio Enrico; Mondino, A; Riva, Giovanni; Vallerini, Daniela; Quadrelli, Chiara; Bosco, Raffaella; Ciceri, F; Bordignon, C; Schulz, Tf; Torelli, Giuseppe; Luppi, Mario
abstract

In nine patients with posttransplant Kaposi sarcoma (KS) T-cell responses to human herpesvirus (HHV)-8 latent and lytic antigens, as detected by enzyme-linked-immunospot (Elispot) assay, were absent at disease onset. Virus-specific T-cell responses were detected in six renal recipients at remission after a reduction of calcineurin inhibitors (CIs), and in two HHV-8 seropositive renal recipients without KS. In two liver recipients undergoing switch from CIs to sirolimus (SRL), normalization of the T-cell repertoire and recovery of both HHV-8-specific effector and memory T lymphocytes were associated with complete KS remission. In a renal recipient undergoing SRL conversion, the early recovery of HHV-8-specific effector but not of memory T lymphocytes, was associated only with partial remission. Neither rejection nor changes in graft function were observed after SRL conversion. HHV-8-specific T-cell responses are required to achieve posttransplant KS remission, and may be restored under SRL, while maintaining effective immunosuppression.

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 - Effects of Everolimus monotherapy on hemathological parameters and iron homeostasis in de novo liver transplant resipients: preliminary results. [Articolo su rivista]
Masetti, Michele; Rompianesi, Gianluca; Montalti, R; Romano, Antonio; Spaggiari, Mario; Ballarin, Roberto; Guerrini, Gian Piero; Gerunda, Giorgio Enrico
abstract

INTRODUCTION: Anemia after orthotopic liver transplantation (OLT) is a common complication due to several reasons. Immunosuppressive drugs play an important role in anemia occurring at 1 month or more after OLT. Several studies describe myelosuppression immunosuppressants such as the mammalian target of rapamycin inhibitors. METHODS: We performed a single-center, prospective trial consisting of a short 30-day course of cyclosporine (CsA) associated with everolimus (EVL) from postoperative day 10 (Group EVL) versus a CsA immunosuppressive regimen (Group CsA) in de novo OLT patients. We explored the influence of immunosuppressive drugs on hematological parameters comparing EVL versus CsA. RESULTS: Twenty-eight patients were enrolled in the EVL and 12 in the CsA Groups. After OLT, hemoglobin (Hb), hematocrit (Hct), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), white blood cell (WBC), platelets (PLT), transferrin saturation (TSAT), iron, ferritin, and transferrin did not differ significantly between the 2 groups at any time point. Among the patients who reached 6-months of follow-up, 5 (41.7%) EVL and 4 (80%) CsA subjects were anemic (P=not significant [NS]). Only anemia in patients enrolled in Group EVL showed a trend toward the features of microcytic, hypochromic anemia. DISCUSSION: Our results demonstrated that de novo anemia in OLT patients treated with EVL monotherapy showed the same incidence as in patients treated with CsA. Hb values remained similar during the entire follow-up. Moreover, overall myelosuppression in the EVL Group was not significantly different from patients in the CsA Group.

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 - 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 - 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 <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 - 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 - 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 - 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 - Pancreas Transplantation Inside Emilia-Romagna, Italy: Referral Pattern, Demand Forecasting, and Organ Availability [Articolo su rivista]
Bonucchi, D; Longhitano, E; Gerunda, Giorgio Enrico; Baldini, A; Masetti, Michele; Ravera, F; DE AMICIS, Sara; Albertazzi, Vittorio; Mori, Giacomo; Savazzi, A; Albertazzi, Alberto
abstract

In Italy, referral of diabetic patients for pancreas transplantation (PT) is an unstructured process, resulting in a low rate of activity and late referrals, often when the patient has already undergone dialysis. In addition, the continuous improvement in pancreas transplant alone, offering the opportunity to reduce cardiovascular risk due to proteinuria and reduced glomerular filtration rate (GFR), is rarely appreciated. We therefore analyzed (1) referral activity to PT during the time frame 2001-2005 in Emilia-Romagna, Italy (four million inhabitants), by collecting ICD 9 CM codes (55.69 + 52.80; 52.86 and 52.80 alone) by residence of the patient; (2) demand for PT among a sample population of 1670 diabetes patients, whose charts were reviewed for the type of diabetes and presence of overt diabetic nephropathy (DN: proteinuria >300 mg/24 h and/or GFR <60 mL/min); (3) potential pancreas availability as the ratio between pancreas and hearts utilized (UP/HR) in different areas of our country. As a results, (1) referral activity reached 8.4 PT per million people in 5 years in the whole region, ranging from 2.6 in the province where a PT program is active, to a maximum value of 20.7 in the province where a devoted outpatient clinic is operated by nephrologists. (2) Prevalence of overt DN was 6% in our cohort, corresponding to 510 D1 patients worthy of evaluation for PT inside Emilia-Romagna region. (3) During 2006, UP/HR was 0.58 in Associazione Inter-Regionale Trapianti agency, 1.16 in Tuscany, 0.30 in Piedmont, and 0.26 in our region. Taken together, our data showed that (1) the referral of D1 to PT has to be empowered, keeping in touch with all patients suffering from diabetic nephropathy; (2) the outpatient clinic devoted to evaluation and recruitment of D1 with nephropathy plays the key role in this program of timely and widespread referral; (3) the availability of pancreata can be increased by utilizing broader criteria for harvesting, increased consent rate to donation and increased the demand for PT (recipient pool). Pancreas grafts need to increase, since the current low demand produces underutilization of the pancreas resource, due to the frequent lack of a suitable recipient.

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 - Use of Recombinant Factor IX and Thromboelastography in a Patient With Hemophilia B Undergoing Liver Transplantation: A Case Report [Articolo su rivista]
Depietri, Luca; Masetti, Michele; Montalti, R; Begliomini, Bruno; Reggiani, Alexia; Barbieri, Elena; Biagioni, Emanuela; Marietta, M; Romano, Antonio; Pasetto, Alberto; Gerunda, Giorgio Enrico
abstract

Hemophilia B is a congenital recessive disorder caused by deficiency of coagulation factor IX (FIX). Surgical procedures can be performed in patients with hemophilia using high-purity and/or recombinant FIX, which has been shown to be safe and effective in surgical hemostasis. Liver transplantation is the only potentially curative treatment available for these patients, providing a long-term phenotypic cure for hemophilia. End-stage liver disease together with hemophilia exposes patients to greater risks of bleeding complications during the perioperative period with consequent difficulties in managing coagulopathy. The limited experiences reported by different investigators and the various strategies for clotting factor replacement make it difficult to define a single approach with respect to the optimal dose and method of administering FIX to achieve perioperative hemostasis. The limits of plasma-based coagulation tests--prothrombin time, activated partial thromboplastin time--have made thromboelastography a valid alternative in this kind of surgery. It has been demonstrated to be a useful tool for real-time analysis of clot formation using a whole-blood assay format. Further, it accurately illustrates the clinical effects of procoagulant or anticoagulant interventions. In this article, we have described the usefulness of thromboelastography to monitor the ability of high-purity FIX supplementation to restore a normal coagulation state and to guide the perioperative administration of blood products in a successful orthotopic liver transplantation in a hemophilic patient with deficiencies of factors IX and X, presenting with hepatitis C virus-related cirrhosis and hepatocellular carcinoma

2008 - What is the biopsychosocial role of human immunodeficiency virus positivity in patients with end-stage liver disease who undergo orthotopic liver transplantation? [Articolo su rivista]
Barbanti Silva, Veronica; Ferrara, Maria; Mazzi, Fausto; Pingani, Luca; Cocchi, Stefania; Romano, Antonio; Masetti, Michele; Gerunda, Giorgio Enrico; Guaraldi, Giovanni; Rigatelli, Marco
abstract

INTRODUCTION: Since 2003 the National Research Program for Solid Organ Transplantation in patients with human immunodeficiency virus (HIV) is active at our liver transplantation center. Patients with HIV who enter this protocol are assessed by the Consultation Liaison Psychiatry Service. The aim of the present study was to evaluate their psychiatric comorbidity. METHODS: An observational prospective study was conducted comparing end-stage liver disease (ESLD) patients with and without HIV. After the assessment, the psychiatrist compiled the Transplant Evaluation Rating Scale (TERS) and the Montgomery Asberg Depression Rating Scale (MADRS). Baseline evaluation was made before inclusion on the OLT waiting list and the follow-up evaluation was made 12 months later. RESULTS: From January 2003 to December 2006 we assessed 553 patients: 39 (6%) with HIV and 361 (94%) without HIV. The 2 groups were homogeneous for gender (75% of male patients; P=not significant [NS]) but not for age (46+/-5 vs 56+/-9; P=NS). Psychiatric history was negative in 176 (49%) patients without HIV and in 6 (15%) patients with HIV (P< .001). At baseline psychiatric comorbidity was present in 33 HIV patients (85%) and in 148 non-HIV patients (41%; P< .001). At follow-up MADRS highlighted an improvement in all of the items for HIV patients. In the non-HIV group, the variation was as follows: baseline, 7.10; follow-up, 8.15. In the HIV group, the variation was as follows: baseline, 10.20; follow-up, 4.09 (P< .001). The average score at TERS was higher among patients with HIV (43+/-9 vs 35+/-9; P=NS). CONCLUSIONS: At baseline HIV patients with ESLD showed a higher rate of psychopathology, but they improved at follow-up; the contrary happened in the non-HIV group.

2008 - What is the role of HIV positivity in patients with ESLD who undergo Oltxiter? [Abstract in Rivista]
Barbanti, Sv; Ferrara, M; Mazzi, F; Pingani, L; Cocchi, S; Guaraldi, Giovanni; Gerunda, Giorgio Enrico; Rigatelli, Marco
abstract

Not available

2008 - What is the role of HIV positivity in patients with ESLD who undergo to OLTx Iter? [Abstract in Rivista]
V., Barbanti Silva; M., Ferrara; L., Pingani; F., Mazzi; S., Cocchi; Guaraldi, Giovanni; A., Romano; M., Masetti; Gerunda, Giorgio Enrico; Rigatelli, Marco
abstract

Not available

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 - 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 - 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 < 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 - 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<0.01). The differences were mainly due to the deaths on the list (8% lab 1 vs. 2.1% lab 2, P<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<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 - NITRIC OXIDE GENERATION IS ASSOCIATED WITH AN UNBALANCE OF PROTEIN TYROSINE PHOSPHATASES DURING LIVER TRANSPLANTATION [Articolo su rivista]
Carlucci, F; Marinello, E; Rosi, F; Floccari, F; Gerunda, Giorgio Enrico; Neri, D; Tabucchi, A.
abstract

Organ dysfunction secondary to ischemia-reperfusion (I/R) injury still represents a major problem in liver transplantation. Apoptosis has been observed in hepatocytes and sinusoidal endothelial cell, following I/R injury and it has been postulated as a contributing factor in ischemia-reperfusion graft dysfunction, involving a complex series of events, as changes of protein tyrosine-kinase phosphorylation. We evaluated hepatic purine metabolites, protein tyrosine phosphatases (PTPs), nitrate plus nitrite levels (NOx), caspase-3 (C-3) activity and DNA fragmentation in the time course of twelve pig orthotopic liver transplantation. Biopsies were taken before explantation (t0), after cold ischemic storage (t1) and 30 min from reperfusion (t2). During the ischemic period we observed a reduction of high energy phosphates and an increase of purine bases; PTP activity was largely increased. At t2 high energy phosphates showed a tendency to increase with respect to t1, with a partial restoration of phosphorylation potential, measured as ATP/ADT ratio. PTP activity was significantly reduced, with a concomitant increase of NOx production and C-3 activity; in a considerable number of cases we observed a sustained DNA fragmentation. We speculate that NOx production could be related to nitrosative stress, which in turn leads to dynamic alteration in PTP balance and cell signalling, regulating the activity of a number of proteins implicated in apoptotic cell death. These findings could be of interest in new potential strategy to prevent and treat I/R injury.

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 - 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.

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 - 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 - 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 - 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 - The use of intrathecal morphine for postoperative pain relief after liver resection: a comparison with epidural analgesia [Articolo su rivista]
Pietri, L. De; Siniscalchi, A.; Reggiani, Alexia; Masetti, Michele; Begliomini, Bruno; Gazzi, Matteo; Gerunda, Giorgio Enrico; Pasetto, Alberto
abstract

An epidural catheter is used in some institutions for postoperative analgesia after liver surgery. However, anesthesiologists may not feel comfortable leaving a catheter in the epidural space because of concern about coagulation disturbances and possible bleeding complications caused by impaired liver function. In this study, we tested a single-shot intrathecal morphine technique and compared it to a continuous epidural naropine infusion for postoperative analgesia in liver surgery. Fifty patients were randomly assigned to an epidural analgesia group (EP group; n = 25) and an intrathecal analgesia group (IN group; n = 25). The quality of analgesia assessed by a visual analog scale (VAS), the side effects, and the additional IV analgesic requirements were recorded. We did not observe any signs of cord compression. Time to first pain drug requirement was longer in the EP group compared to the IN group (25 +/- 18.5 h versus 12 +/- 10.3 h; P < 0.05). In both groups, the VAS remained less than 30 mm throughout the 48-h follow-up period. Consumption of IV morphine with a patient-controlled analgesia device in the IN group was larger (mostly from 24 to 48 h after surgery) than the EP group (12.0 +/- 5.54 mg versus 3.1 +/- 2.6 mg, respectively; P < 0.01). The incidence of vomiting was 4% in both groups, whereas the incidence of pruritus (16% versus 0%) and nausea (16% versus 4%) was more frequent in the IN group. No postdural puncture headache and no spinal hematoma occurred. After liver resection, a single dose of intrathecal morphine followed by patient-controlled morphine analgesia can provide satisfactory postoperative pain relief. The quality of this treatment, according to the VAS, is not inferior to continuous epidural analgesia up to 48 h after surgery.

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 - 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 - 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 - A COMPARATIVE PROSPECTIVE STUDY OF TWO AVAILABLE SOLUTIONS FOR KIDNEY AND LIVER PRESERVATION [Articolo su rivista]
Pedotti, P; Cardillo, M; Rigotti, P; Gerunda, Giorgio Enrico; Merenda, R; Cillo, U; Zanus, G; Baccarani, U; Berardinelli, Ml; Boschiero, L; Caccamo, L; Calcoli, G; Chiaramonte, S; Dalcanton, A; Decarlis, V; V, DI CARLO; Donati, Donatella; Montanaro, D; Pulvirenti, Andrea; Remuzzi, G; Sandrini, S; Valente, U; Scalamogna, M.
abstract

BACKGROUND: Viaspan (University of Wisconsin [UW]) solution is the gold standard for abdominal organ preservation. Celsior (CEL) is an extracellular-type, low-potassium, low-viscosity solution, initially used for heart and lung preservation. We have performed a prospective multicenter study to compare the role of these cold-storage solutions on kidney and liver recovery after transplantation. PATIENTS AND METHODS: From March 15, 2000 to December 31, 2001, 441 (172 CEL and 269 UW) renal transplants (RT) and 175 (79 CEL and 96 UW) liver transplants (LT) were included in the study. RESULTS: Perfusate volume used was significantly lower in the UW group, being 4,732 +/- 796 mL versus 5,826 + 834 mL in the CEL group (P < 0.001). In LT, median total bilirubin serum levels were significantly higher at 5 and 7 posttransplant days in the UW group (90.6 and 92.3 micromol/L, respectively) as compared with CEL (51.3 and 63.4 micromol/L, respectively). After LT, primary nonfunction (PNF) rates in the CEL and UW groups were 3.8% and 4.2% (P = NS) respectively, with 1-year graft and patient survival being 83.3% versus 85.4% (P = NS) and 89.9% versus 90.6% (P = NS). After RT, delayed graft function (DGF) rates were 23.2% and 22.7% (P = NS), respectively; PNF rates were 1.9% and 1.7% (P = NS) respectively, with 1-year graft and patient survival being 92.3% versus 94.2% (P = NS) and 99.4% versus 97.7% (P = NS). CONCLUSIONS: CEL solution was shown to be as effective as UW in both liver and kidney preservation. In LT patients, biliary function recovery is significantly better in the CEL group. CEL solution represents an efficacious option in multiorgan harvesting.

2004 - LIVER TRANSPLANT: ADENOSINE METABOLISM AND APOPTOSIS [Articolo su rivista]
Carlucci, F; Marinell, E; Gerunda, Giorgio Enrico; Neri, D; Rosi, F; Floccari, F; Tabucchi, A.
abstract

Apoptosis and necrosis coexist in ischemia-reperfusion (I/R) injury following organ transplant. During experimental liver transplant we evidenced a deep alteration in energy and antioxidant status. The activity of purine catabolic enzymes was also altered. Caspase-3 (C-3), protein tyrosine phosphatase (PTP) showed significative alterations that lead to DNA fragmentation. These findings could be of interest in new potential strategy to prevent and treat I/R injury.

2002 - A RANDOMIZED CONTROLLED TRIAL OF MEDICAL THERAPY VERSUS ENDOSCOPIC LIGATION FOR THE PREVENTION OF VARICEAL REBLEEDING IN PATIENTS WITH CIRRHOSIS [Articolo su rivista]
Patch, D.; Sabin, A.; Goulis, J.; Gerunda, Giorgio Enrico; Greenslade, L; Merkel, C; Burroughs, Ak
abstract

BACKGROUND & AIMS: Patients who have had one variceal bleed are at high risk of rebleeding. Since its introduction, endoscopic variceal banding has been shown to be superior to needle sclerotherapy. Banding has not been compared with hepatic venous pressure-guided medical therapy (beta-blockers and nitrates). METHODS: One hundred two patients with cirrhosis and a recent esophageal variceal bleed were randomized to either endoscopic banding (51 patients) or medical therapy (51 patients). The hepatic venous pressure gradient was measured in all patients at baseline, at 3 months (drug therapy arm), and at yearly intervals (all patients). Primary end points were death or rebleeding. RESULTS: The 2 groups were well matched. Fifty-one percent were Pughs C, with a median Pughs score of 9.5. Nineteen patients rebled in the drug arm (median time, 24 days) and 27 patients in the banding arm (median time, 24 days). At 1 year, 43.7% of patients had bled in the drug arm compared with 53.8% in the banding arm (P = 0.25). Thirty-two percent of patients on medical therapy had died at 1 year, 22.5% on banding (P = 0.97). CONCLUSIONS: In the prevention of variceal rebleeding, beta-blockers +/- nitrates are as effective as endoscopic banding.

2002 - Cavoportal hemitransposition: A successful way to overcome the problem of total portosplenomesenteric thrombosis in liver transplantation [Articolo su rivista]
Gerunda, G.; Merenda, R; Neri, D; Angeli, P; Barbazza, F; Valmasoni, M; Zangrandi, F; Gangemi, A; Miotto, D; Gagliesi, A; MAFFEI FACCIOLI, A
abstract

Orthotopic liver transplantation (OLT) may be feasible even in the presence of diffuse portal vein thrombosis (PVT) in the recipient, providing hepatopetal portal flow to the graft can be ensured. Cavoportal hemitransposition was used in selected cases in which no other salvage solutions were technically possible. We report our experience of two patients with diffuse thrombosis of the entire portal system. One patient also had thrombosis of a previous portacaval shunt with a synthetic interposition graft. Portal pedicle dissection and native hepatectomy (with or without vena cava removal) appeared difficult. Bleeding from the exposed area was severe, and in one case, a new laparotomy was necessary to stop the abdominal hemorrhage. The postoperative course was complicated by severe ascites (with fluid infection and surgically drained suprahepatic abscess in one case), renal insufficiency (requiring dialysis in one case), esophagogastric variceal bleeding (needing several sessions of endoscopic treatment), and bronchopneumonic infections (in one case, superinfection with Aspergillus fumigatus despite amphotericin B lipid complex therapy led to the patient's death from multiorgan failure). Our experience was compared with 17 other cases in the literature. Etiologic factors, preoperative diagnostics, surgical problems, and postoperative complications are focused on and discussed. Diffuse PVT no longer appears to be an absolute contraindication to OLT, although cavoportal hemitransposition needs further experience and long-term follow-up.

2002 - HEPATOCYTE TRANSPLANTATION AS A TREATMENT FOR GLYCOGEN STORAGE DISEASE TYPE 1a [Articolo su rivista]
Muraca, M.; Gerunda, G.; Neri, D.; Vilei, Mt; Granato, A.; Feltracco, P.; Meroni, M.; Giron, G.; Burlina, Ab
abstract

Treatment of many inherited disorders of hepatic metabolism is still challenging. Hepatocyte transplantation was done in a 47-year-old woman who had glycogen storage disease type 1a and severe fasting hypoglycaemia. 2 billion viable hepatocytes were infused via an indwelling portal-vein catheter, followed by a triple immunosuppression regimen with mycophenolate mofetil, tacrolimus, and steroids. 9 months after transplantation, on only tacrolimus, she eats a normal diet and can fast for 7 h without experiencing hypoglycaemia. Our results show that hepatocyte transplantation might be an alternative to liver transplantation in glycogen storage disease type 1a.

2002 - INTRAPORTAL HEPATOCYTE TRANSPLANTATION IN THE PIG: A HEMODYNAMIC AND HISTOPATHOLOGICAL STUDY [Articolo su rivista]
Muraca, M; Neri, D; Parenti, A; Feltracco, P; Granato, A; Vilei, Mt; Ferraresso, C; Ballarin, R; Zanusso, Ge; Giron, G; Gerunda, Giorgio Enrico
abstract

BACKGROUND: Hepatocyte transplantation is an attractive treatment for various liver diseases. The intraportal route of transplantation is favored, but little information is available on the possible adverse effects in this technique. We investigated the influence of intraportal loads of hepatocytes on portal, pulmonary, and systemic hemodynamics in 13 pigs. METHODS: Under general anesthesia, pigs were provided with an arterial line, a Swan-Ganz catheter, and two intraportal catheters, one for cell infusion and one for heparin infusion and portal pressure measurement. Pig hepatocytes were infused at a rate of 25 million cells/min. RESULTS: The first six animals were used to develop the infusion technique. In the last seven animals, portal pressure increased linearly with cell load upon infusion of 400-2400 x 10(6) hepatocytes (r(2)=0.704;P<0.05). Portal flow measured by Doppler sonography decreased by 23-66% below basal values. An inverse linear relationship was found between portal pressure and portal flow (r(2)=0.679; P<0.05), portal flow approaching zero for portal pressure >40 mmHg. Pulmonary arterial pressure increased by 11-62%. AST increased up to 10-fold, and platelets decreased by 22-58%. Hepatocytes-containing thrombi were present in segmental and in smaller portal branches. Hepatocytes were always identified in lung sinusoids 48 hr after infusion, and a small basal pulmonary infarction was found in one animal. CONCLUSION: . These data suggest that up to 2.4% of total hepatocyte mass can be infused in this large animal model. However, the risk of significant thrombotic complications should be considered for clinical applications.

2001 - LIVER TRANPLANTATION WITH VENA CAVA IN SITU AND SELECTIVE USE OF TEMPORARY PORTA CAVAL SHUNT OR PORTAL CLAMPING [Articolo su rivista]
Gerunda, Giorgio Enrico; Merenda, R; Neri, D; Barbazza, F; Dimarzio, E; Zangrandi, F; Meduri, F; Bisello, M; Valmasono, M; MAFFEI FACCIOLI, A.
abstract

BACKGROUND/AIMS: The recipient hepatectomy with vena cava in situ in liver transplantation has overcome the need of venous-venous bypass thanks to temporary porta caval shunt or portal clamping. METHODOLOGY: 150 orthotopic liver transplants in 137 patients were performed and the vena cava in situ technique was used in 142 (venous bypass in 7, temporary porta caval shunt in 49, portal clamping in 87). The suprahepatic cava veins anastomosis was performed with Belghiti in 97 and piggyback techniques in 45. RESULTS: There were no differences in operative and warm ischemia times nor in blood requirements, while a greater stability of body temperature was documented in the vena cava In Situ group: in the latter temporary porta caval shunt preserved the temperature better than portal clamping (P < 0.01). In anhepatic phase mean artery pressure decreased in veno-venous bypass and increased in the vena cava In situ groups (P < 0.01). The venous return and the cardiac performances (anhepatic phase) were better preserved in the vena cava In Situ group. (P < 0.0001). CONCLUSIONS: Temporary portal caval shunt or portal clamping and piggyback or Belgiti Techniques allow a better hemodynamic stability through out the procedure, obviating the need for veno-venous bypass or fluid overload, if selectively used.

2001 - TACROLIMUS BASED DUAL THERAPY IS AS EFFECTIVE AND SAFE AS THE CONVENTIONAL TACROLIMUS TRIPLE THERAPY IN LIVER TRANSPLANTATION? [Articolo su rivista]
Salizzoni, M; Cavallari, A; Risaliti, A; Filipponi, F; Gerunda, Giorgio Enrico; Forti, D; Fassati, Lr; Cillo, U; Castagneto, M; Valente, U; Tisone, G.
abstract

Tacrolimus-based dual therapy is as efficacious and safe as the conventional tacrolimus-based triple therapy in liver transplantation.

2000 - IS INTRAPORTAL HEPATOCYTE TRANPLANTATION A SAFE PROCEDURE? A STUDY IN LARGE ANIMAL MODEL [Articolo su rivista]
Muraca, M; Neri, D; Gerunda, Giorgio Enrico; Feltracco, P; Parenti, A; Granato, A; Vilei, Mt; Ferraresso, C; Ballarin, R; Zanusso, E; Rozgaj, ; Giron, Gp
abstract

IS INTRAPORTAL HEPATOCYTE TRANPLANTATION A SAFE PROCEDURE? A STUDY IN LARGE ANIMAL MODEL

2000 - LIVER KIDNEY TRANSPLANTATION IN TYPE 1 PRIMARY OXALURIA:DESCRIPTIONAND COMMENTS ON A CASE. [Articolo su rivista]
Gambaro, G; Lidestri, V; Gerunda, Giorgio Enrico; Zavan, Mc; Iemmolo, Rm; Rigotti, P; Naso, A; Antonello, A; D'Angelo, A.
abstract

BACKGROUND: Primary hyperoxaluria leads to oxalosis, a systemic illness with fatal prognosis in uremic youngsters because of systemic complications. CASE REPORT: A 14-year old boy with primary type 1 hyperoxaluria who had a long-lasting history of nephrolithiasis and passed from normal renal function to end-stage renal disease within 7 months. MEASUREMENT of alanine: glyoxylate aminotransferase (AGT) catalytic activity in the liver biopsy disclosed very low activity which was not. responsive to pyridoxin., thus the patient entered onto a priority national waiting list for liver-kidney transplantation and a week later received a combined transplant. In order to increase body clearance of oxalate, the patient underwent medical treatment to increase urine oxalate solubility (sodium and potassium citrate oral therapy, magnesium supplementation and increase of diuresis) and intensive dialysis both before and after transplantation. COMMENT: The medical approach to the treatment of this rare illness is discussed. Since the major risk for the grafted kidney is related to the oxalate burden, i.e. oxalate deposition from the body deposits to the kidney that becomes irreversibly damaged, treatment consists of increasing the body clearance of oxalate both by increasing oxalate solubility in the urine and with intensive dialysis performed both before and after combined transplantation. To the same extent (by limiting body oxalate deposits), a relatively early (native GFR 20-25 ml/minute) transplantation is advisable.

2000 - Long term persistence of low bone density in orthotopic liver transplantation [Articolo su rivista]
Giannini, S.; Iemmolo, R. M.; Gerunda, Giorgio Enrico; Crepaldi, G.; Destro, C.
abstract

We determined bone density and metabolism in 46 patients (35 males, 11 females) who had undergone liver transplantation 1-48 months previously. Twenty-one patients were then followed for the next 24 months. At each visit, blood and urine samples for bone and liver metabolism parameters, as well as spinal and femoral dual-energy X-ray absorptiometry (DXA) scans, were obtained. Basal spinal and femoral density was low (p < 0.001). Patients with pre-transplant cholestatic diseases had lower spinal density than all the other subjects (p <0.05) and the cumulative methylprednisolone intake was an independent negative predictor of total hip density (p < 0.02). At baseline, urinary hydroxyproline and N-telopeptide were at the upper normal level and decreased only after 24 months of follow-up (p < 0.05). During the first year of follow-up, femoral density decreased (p < 0.05) and a partial recovery was observed for both spine and femur after 24 months. After 12 months, femoral bone density was negatively associated with serum cyclosporin A levels (p < 0.005) and cumulative methylprednisolone intake (p < 0.05), while the percent decrease in spinal density after the first 12 months was negatively predicted by mean daily methylprednisolone intake (p < 0.05). In patients with pre-transplant cholestatic diseases, femoral and spinal density increased after the first (p < 0.05) and second year (p < 0.05), respectively. In patients with previous post-necrotic cirrhosis, femoral density decreased after 12 months (p<0.05) and was still lower than baseline after 24 months (p < 0.05). However, at the end of the study the cumulative percentage of femoral neck osteoporosis was 43%. In conclusion, an elevated prevalence of spinal and femoral osteoporosis is present even many years after liver transplantation, with immunosuppressive treatment and pre-transplant liver disease being the most important pathogenetic factors.

2000 - Role of transarterial Chemoembolization Befero Liver Resection For Hepatocarcinoma [Articolo su rivista]
Gerunda, G.; Neri, D.; Merenda, R.; Barbazza, F.; MAFFEI FACCIOLI, A.
abstract

The aim of this study was to clarify whether chemoembolization (TACE) before liver resection (LR) can reduce postoperative hepatocellular carcinoma (HCC) recurrence and improve disease-free and overall survival. Eighty-nine patients with tumor-stage (TNM) I-II HCC were evaluated for LR. Patients were prospectively allocated to LR alone or TACE plus LR based on their place of residence. Twenty nonlocal patients (24%) were selected for LR, while 69 (77.5%) local patients were selected for TACE plus LR. Following TACE, the tumor stage could be confirmed in only 20 patients (29%) who then underwent LR. Operative mortality was 0%, but in the TACE-LR group, 3 patients died of liver failure between 2 and 5 months after surgery. Early recurrence (<24 months) was 59% for LR versus 20% for TACE plus LR (P <.05). Late recurrence was 18% for LR versus 10% for TACE plus LR (P = not significant [NS]). The overall recurrence rate was 76% for LR versus 30% for TACE plus LR (P <.02). Death due to HCC recurrence was 70% for LR versus 15% for TACE plus LR (P <.05). The overall 1- and 5-year survival rates did not differ significantly (71% to 38% for LR v 85% to 43% for TACE + LR; P = NS), whereas the difference in 1- and 5-year disease-free survival was highly significant (64% to 21% for LR v 82% to 57% for TACE + LR; P <.02). TACE was able to improve the HCC staging process and significantly reduce the incidence of early and overall HCC recurrence and related death after LR; it improved the disease-free interval, but not the overall survival, due to an increase in liver failure in the first 5 months.

1998 - Cerebral Aspergillosis in a liver transplant recipient [Articolo su rivista]
Iemmolo, Rm; Rossanese, A; Gerunda, G.; Neri, D; Strazzabosco, M
abstract

Cerebral aspergillosis is a life-threatening complication in liver transplant recipients, with mortality rates approaching 100%; treatment with amphotericin B is of limited efficacy because of its poor distribution in the cerebrospinal fluid and its systemic side effects. We report the case of a liver transplant recipient who developed recurrent cerebral Aspergillus fumigatus infection, and was successfully treated by combined surgical excision of the lesion and administration of liposomal amphotericin B. This first report of long-term complication-free survival in a liver transplant recipient suggests that therapy with liposomal amphotericin B may reduce the risk of recurrence of cerebral aspergillosis in these immunocompromised patients. PMID:9551693[PubMed - indexed for MEDLINE]

1998 - SPLENIC IMPEDANCE INDICES:A USEFUL METHOD TO MONITOR PATIENTS AFTER LIVER TRANPLANTATION? [Articolo su rivista]
Bolognesi, M; Sacerdoti, D; Bombonato, G; Angeli, P; Gerunda, Giorgio Enrico; Merenda, R; Volpin, R; Iemmolo, Rm; Gatta, A.
abstract

Splenic Doppler impedance indices are influenced, in portal hypertensive patients, by the resistance of the portal system. The aim of the study was to verify the usefulness of these indices in evaluating the presence of a pathological increase in portal resistance in patients with complications after liver transplantation. Splenic impedance indices have been evaluated in 46 patients before orthotopic liver transplantation (OLT), and 2 days, 1, 4, 8, and 12 to 18 months after transplantation. The results showed that spleen size slowly decreased after liver transplantation. From a baseline longitudinal diameter value of 18.0+/-3.6 cm (M+/-SD), the decrease was by 0%+/-3%, 8%+/-8%, 13%+/-9%, 15%+/-11%, and 14%+/-11% at 2 days and 1, 4, 8, and 12 to 18 months after liver transplantation. Splenic impedance indices-resistance index = (peak systolic - end diastolic) / peak systolic velocity; pulsatility index = (peak systolic - end diastolic) / mean velocity-which were increased before liver transplantation, showed a rapid decrease to normal values: resistance index: from 0.62+/-0.08 to 0.55+/-0.08 after 2 days, and to 0.49+/-0.09, 0.51+/-0.10, 0.54+/-0.10, 0.55+/-0.11 after 1, 4, 8, 12-18 months; pulsatility index: from 0.96+/-0.21 to 0.82+/-0.17 after 2 days, and to 0.69+/-0.19,0.72+/-0.21, 0.81+/-0.26, 0.84+/-0.26 after 1, 4, 8, and 12 to 18 months. Patients who had a good outcome, without any major complications, showed a clear and steady decrease in splenic impedance indices. On the contrary, patients who had complications affecting portal resistance (e.g., acute rejection, relapse of chronic hepatitis C virus-related hepatitis or cirrhosis, stenosis of portal anasthomosis, portal thrombosis), showed a lack of decrease, or, after an initial decrease, a subsequent re-increase in splenic impedance indices to pathological values. Splenic impedance indices measured in patients with complications were higher than those of patients without complications (P < .0004). Specificity and sensitivity of splenic impedance indices in the evaluation of the presence of complications increasing portal resistance were good. In conclusion, after OLT, splenic impedance indices could be useful aspecific parameters for identifying patients with complications that are able to affect or increase portal resistance.

1997 - Combined liver and islet transplantation:about one case [Articolo su rivista]
Merenda, R; Gerunda, Giorgio Enrico; Neri, D; Iemmolo, Rm; MAFFEI FACCIOLI, A.
abstract

Combined liver and islet transplantation: about one case.

1997 - Epstein-Barr virus associated PTLD of donor origin in liver transplant recipients [Articolo su rivista]
Strazzabosco, M; Iemmolo, Rm; Gerunda, Giorgio Enrico; Neri, D; D'Andrea, E.
abstract

BACKGROUND/AIMS: Post-transplant lymphoproliferative disease, a potential complication of solid organ transplantation, occurs in about 3% of orthotopic liver transplant recipients. We report the genetic and virological characterization of two cases of post-transplant lymphoproliferative disease that occurred early (4 and 6 months) after orthotopic liver transplant as large-cell non-Hodgkin's lymphomas located at the hepatic hilum. METHODS: Lymphomatous tissues were analyzed for clonality and presence of Epstein-Barr virus (EBV) sequences by Southern blot, polymerase chain reaction, and in situ hybridization techniques. RESULTS: The tumors in both cases were sustained by a clonal proliferation of B lymphocytes containing type A EBV DNA. Moreover, in situ hybridization with a digoxigenin-labeled EBV-specific probe evidenced a strong nuclear signal in most of the neoplastic cells. DNA microsatellite analysis at three different loci detected alleles of donor origin in both tumor samples, suggesting that the neoplastic B cells were of donor origin. CONCLUSIONS: EBV-infected donor B lymphocytes might be responsible for intragraft post-transplant lymphoproliferative disease in orthotopic liver transplant recipients. As 20 to 30% of post-transplant lymphomas involve the graft itself, donor-derived post-transplant lymphoproliferative disease might be more frequent than presently appreciated. Prospective studies are needed to assess its real incidence and identify possible risk factors.

1997 - Infrahepatic terminolateral cavo-cavostomy as rescue technique in complicated "modified" piggyback liver transplantation [Articolo su rivista]
Merenda, R; Gerunda, Giorgio Enrico; Neri, D; DI MARZIO, E; Faccioli, A.
abstract

Infrahepatic terminolateral cavo-cavostomy as a rescue technique in complicated "modified" piggyback liver transplantation.

Università degli studi di Modena e Reggio Emilia

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