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Alexandre ANESI

Professore Associato
Dipartimento di Scienze Mediche e Chirurgiche Materno-Infantili e dell'Adulto

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2023 - An Analysis of Volume, Length and Segmentation of Free Fibula Flap in Reconstruction of the Jaws: Investigation of Their Role on Flap Failure [Articolo su rivista]
Di Bartolomeo, M; Lusetti, Il; Pinelli, M; Negrello, S; Pellacani, A; Angelini, S; Chiarini, L; Nocini, R; De Santis, G; Anesi, A

Reconstruction of defects of the jaws is mainly performed via free fibula flap. An incidence of 2-21% of overall flap failure is still described. We investigated the roles of volume, length and number of fibula flap segments on flap survival using novel three-dimensional segmentation tools. We also analyzed the role of other possible risk factors. Seventy-one consecutive patients with a follow up of at least three months and who underwent free fibula flap reconstruction in a single center between 2002 and 2022 have been evaluated. A total of 166 fibula segments were analyzed. Malignancies were the main reason of resection (45.1%). In 69% of the cases a reconstruction of the mandible was performed. The flaps were mainly divided in two segments (39%) (range 1-4), with a mean length of 2.52 cm and a mean volume was 3.37 cm(3). Total flap failure (TFF) occurred in 12 cases, (16.9%), while partial flap failure (PFF) appeared in 3 patients (4.2%). Volume, length and number of fibula flap segments did not seem to influence flap failure incidence in uni- and multivariate analysis. Reconstruction of the maxilla and use of a recipient vessel different from the facial artery seemed to significantly impact on flap failure. Smoking and previous surgeries showed a higher trend to flap failure, but they did not reach statistical significance. Prospective and multicentric analysis on a wider population should be assessed.

2023 - Inferior Alveolar Canal Automatic Detection with Deep Learning CNNs on CBCTs: Development of a Novel Model and Release of Open-Source Dataset and Algorithm [Articolo su rivista]
Di Bartolomeo, Mattia; Pellacani, Arrigo; Bolelli, Federico; Cipriano, Marco; Lumetti, Luca; Negrello, Sara; Allegretti, Stefano; Minafra, Paolo; Pollastri, Federico; Nocini, Riccardo; Colletti, Giacomo; Chiarini, Luigi; Grana, Costantino; Anesi, Alexandre

Introduction: The need of accurate three-dimensional data of anatomical structures is increasing in the surgical field. The development of convolutional neural networks (CNNs) has been helping to fill this gap by trying to provide efficient tools to clinicians. Nonetheless, the lack of a fully accessible datasets and open-source algorithms is slowing the improvements in this field. In this paper, we focus on the fully automatic segmentation of the Inferior Alveolar Canal (IAC), which is of immense interest in the dental and maxillo-facial surgeries. Conventionally, only a bidimensional annotation of the IAC is used in common clinical practice. A reliable convolutional neural network (CNNs) might be timesaving in daily practice and improve the quality of assistance. Materials and methods: Cone Beam Computed Tomography (CBCT) volumes obtained from a single radiological center using the same machine were gathered and annotated. The course of the IAC was annotated on the CBCT volumes. A secondary dataset with sparse annotations and a primary dataset with both dense and sparse annotations were generated. Three separate experiments were conducted in order to evaluate the CNN. The IoU and Dice scores of every experiment were recorded as the primary endpoint, while the time needed to achieve the annotation was assessed as the secondary end-point. Results: A total of 347 CBCT volumes were collected, then divided into primary and secondary datasets. Among the three experiments, an IoU score of 0.64 and a Dice score of 0.79 were obtained thanks to the pre-training of the CNN on the secondary dataset and the creation of a novel deep label propagation model, followed by proper training on the primary dataset. To the best of our knowledge, these results are the best ever published in the segmentation of the IAC. The datasets is publicly available and algorithm is published as open-source software. On average, the CNN could produce a 3D annotation of the IAC in 6.33 s, compared to 87.3 s needed by the radiology technician to produce a bidimensional annotation. Conclusions: To resume, the following achievements have been reached. A new state of the art in terms of Dice score was achieved, overcoming the threshold commonly considered of 0.75 for the use in clinical practice. The CNN could fully automatically produce accurate three-dimensional segmentation of the IAC in a rapid setting, compared to the bidimensional annotations commonly used in the clinical practice and generated in a time-consuming manner. We introduced our innovative deep label propagation method to optimize the performance of the CNN in the segmentation of the IAC. For the first time in this field, the datasets and the source codes used were publicly released, granting reproducibility of the experiments and helping in the improvement of IAC segmentation.

2023 - In-vivo evaluations of bone regenerative potential of two novel bioactive glasses [Articolo su rivista]
Anesi, A.; Ferretti, M.; Salvatori, R.; Bellucci, D.; Cavani, F.; Di Bartolomeo, M.; Palumbo, C.; Cannillo, V.

: Due to the aging of population, materials able to repair damaged tissues are needed. Among others, bioactive glasses (BGs) have attracted a lot of interest due to their outstanding properties both for hard and soft tissues. Here, for the first time, two new BGs, which gave very promising results in preliminary in vitro-tests, were implanted in animals in order to evaluate their regenerative potential. The new BGs, named BGMS10 and Bio_MS and containing specific therapeutic ions, were produced in granules and implanted in rabbits' femurs for up to 60 days, to test their biocompatibility and osteoconduction. Additionally, granules of 45S5 Bioglass® were employed and used as a standard reference for comparison. The results showed that, after 30 days, the two novel BGs and 45S5 displayed a similar behavior, in terms of bone amount, thickness of new bone trabeculae and affinity index. On the contrary, after 60 days, 45S5 granules were mainly surrounded by wide and scattered bone trabeculae, separated by large amounts of soft tissue, while in BGMS10 and Bio_MS the trabeculae were thin and uniformly distributed around the BG granules. This latter scenario could be considered as more advantageous, since the features of the two novel BG granules allowed for the neo-formation of a uniformly distributed bony trabeculae, predictive of more favorable mechanical behavior, compared to the less uniform coarse trabeculae, separated by large areas of soft tissue in 45S5 granules. Thus, BGMS10 and Bio_MS could be considered suitable products for tissue regeneration in the orthopedic and dental fields.

2023 - Multiple General Anesthesia in Children: A Systematic Review of Its Effect on Neurodevelopment [Articolo su rivista]
Colletti, G.; Di Bartolomeo, M.; Negrello, S.; Geronemus, R. G.; Cohen, B.; Chiarini, L.; Anesi, A.; Femino, R.; Mariotti, I.; Levitin, G. M.; Rozell-Shannon, L.; Nocini, R.

The effect of multiple general anesthesia (mGA) procedures administered in early life is a critical theme and has led the Food and Drug Administration (FDA) to issue an alert. This systematic review seeks to explore the potential effects on neurodevelopment of mGA on patients under 4 years. The Medline, Embase and Web of Science databases were searched for publications up to 31 March 2021. The databases were searched for publications regarding “children multiple general anesthesia OR pediatric multiple general anesthesia”. Case reports, animal studies and expert opinions were excluded. Systematic reviews were not included, but they were screened to identify any possible additional information. A total of 3156 studies were identified. After removing the duplicates, screening the remaining records and analyzing the systematic reviews’ bibliography, 10 studies were considered suitable for inclusion. Comprehensively, a total cohort of 264.759 unexposed children and 11.027 exposed children were assessed for neurodevelopmental outcomes. Only one paper did not find any statistically significant difference between exposed and unexposed children in terms of neurodevelopmental alterations. Controlled studies on mGA administered before 4 years of age support that there might be a greater risk of neurodevelopmental delay in children receiving mGA, warranting the need for careful risk/benefit considerations.

2023 - Primary Mandibular Condyle Xanthoma: Case Report and Literature Review [Articolo su rivista]
Negrello, S; Pellacani, A; Di Bartolomeo, M; Pollastri, G; Anesi, A

Bone xanthoma is a rare benign primary bone lesion histologically characterized by sheets of foamy cells which are macrophages with a cytoplasm filled with droplets of fat. It is usually associated with endocrine or metabolic diseases, in the absence of which the lesion is called primary xanthoma. Because of the lack of pathognomonic radiologic and clinical features, they require a differential diagnosis with a broad spectrum of lesions with a varying degree of malignant potential. We describe a case of primary mandibular xanthoma of a 16-year-old girl without typical cutaneous manifestations and alterations in lipid values. The temporomandibular joint involvement at the mandibular condyle is peculiar in the case described here. We present even a qualitative systematic review of the literature on primary xanthoma of the jaws in others to draw up treatment guidelines.

2023 - Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries [Articolo su rivista]
Adisa, Adewale; Bahrami-Hessari, Michael; Bhangu, Aneel; George, Christina; Ghosh, Dhruv; Glasbey, James; Haque, Parvez; Ingabire, J C Allen; Kamarajah, Sivesh Kathir; Kudrna, Laura; Ledda, Virginia; Li, Elizabeth; Lillywhite, Robert; Mittal, Rohin; Nepogodiev, Dmitri; Ntirenganya, Faustin; Picciochi, Maria; Simões, Joana Filipa Ferreira; Booth, L; Elliot, R; Kennerton, A S; Pettigrove, K L; Pinney, L; Richard, H; Tottman, R; Wheatstone, P; Wolfenden, John W D; Smith, A; Sayed, A Emad; Goswami, Aakansha Giri; Malik, Aamer; Mclean, Aaron Lawson; Hassan, Abbas; Nazimi, Abd Jabar; Aladna, Abdallah; Abdelgawad, Abdalrahman; Saed, Abdel; Abdelmageed, Abdelfatah; Ghannam, Abdelilah; Mahmoud, Abdelrahman; Alvi, Abdul; Ismail, Abdulaziz; Adesunkanmi, Abdulhafiz; Ebrahim, Abdulla; Al-Mallah, Abdullah; Alqallaf, Abdullah; Durrani, Abdullah; Gabr, Abdullah; Kirfi, Abdullahi Musa; Altaf, Abdulmalik; Almutairi, Abdulmjeed; Sabbagh, Abdulrahman J; Ajiya, Abdulrazak; Haddud, Abdurrahman; Alnsour, Abed Alfattah Mahmoud; Singh, Abhinav; Mittal, Abhishek; Semple, Abigail; Adeniran, Abiodun; Negussie, Abraham; Oladimeji, Abraham; Muhammad, Abubakar Bala; Yassin, Abubaker; Gungor, Abuzer; Tarsitano, Achille; Soibiharry, Adaiah; Dyas, Adam; Frankel, Adam; Peckham-Cooper, Adam; Truss, Adam; Issaka, Adamu; Ads, Adel Mohamed; Aderogba, Adeleke Akeem; Adeyeye, Ademola; Ademuyiwa, Adesoji; Sleem, Adham; Papa, Adrian; Cordova, Adriana; Appiah-Kubi, Adu; Meead, Adullah; Nacion, Aeris Jane D; Michael, Afieharo; Forneris, Agustin Albani; Duro, Agustin; Gonzalez, Agustin Rodriguez; Altouny, Ahmad; Ghazal, Ahmad; Khalifa, Ahmad; Ozair, Ahmad; Quzli, Ahmad; Haddad, Ahmad; Othman, Ahmad Faidzal; Yahaya, Ahmad Shuib; Elsherbiny, Ahmed; Nazer, Ahmed; Tarek, Ahmed; Abu-Zaid, Ahmed; Al-Nusairi, Ahmed; Azab, Ahmed; Elagili, Ahmed; Elkazaz, Ahmed; Kedwany, Ahmed; Nuhu, Ahmed Mohammed; Sakr, Ahmed; Shehta, Ahmed; Shirazi, Ahmed; Mohamed, Ahmed Mohamed Ibrahim; Sherif, Ahmed Elshawadfy; Awad, Ahmed K; Abbas, Ahmed M; Abdelrahman, Ahmed Saber; Ammar, Ahmed Siddique; Azzam, Ahmed Y; Ciftci, Ahmet Burak; Dural, Ahmet Cem; Sanli, Ahmet Necati; Rahy-Martín, Aida Cristina; Tantri, Aida Rosita; Khan, Aimal; Al-Touny, Aiman; Tariq, Aiman; Gmati, Aimen; Costas-Chavarri, Ainhoa; Auerkari, Aino; Landaluce-Olavarria, Aitor; Puri, Ajay; Radhakrishnan, Ajay; Ubom, Akaninyene Eseme; Pradhan, Akhilesh; Turna, Akif; Adepiti, Akinfolarin; Kuriyama, Akira; Kassam, Al-Faraaz; Hassouneh, Ala; El-Hussuna, Alaa; Habeebullah, Alaa; Ads, Alaa Mohamed; Mousli, Alaa; Biloslavo, Alan; Hoang, Alan; Kirk, Alan; Santini, Alasdair; Melero, Alba Vazquez; Calvache, Albaro José Nieto; Baduell, Albert; Chan, Albert; Abrate, Alberto; Balduzzi, Alberto; Sánchez, Alberto Cabañero; Navarrete-Peón, Alberto; Porcu, Alberto; Brolese, Alberto; Barranquero, Alberto G; Saibene, Alberto Maria; Adam, Albushra Altayeb; Vagge, Aldo; Maquilón, Alejandra Jara; Leon-Andrino, Alejandro; Sekulić, Aleksandar; Trifunovski, Aleksandar; Mako, Aleksandro; Bedada, Alemayehu Ginbo; Broglia, Alessandro; Coppola, Alessandro; Giani, Alessandro; Grandi, Alessandro; Iacomino, Alessandro; Moro, Alessandro; D’Amico, Alessia; Malagnino, Alessia; Tang, Alethea; Doyle, Alex; Alfieri, Alex; Haynes, Alex; Wilkins, Alex; Baldwin, Alexander; Heriot, Alexander; Laird, Alexander; Lazarides, Alexander; O'Connor, Alexander; Trulson, Alexander; Rokohl, Alexander Christopher; Caziuc, Alexandra; Triantafyllou, Alexandra; Anesi, Alexandre; Nikova, Alexandrina; Andrianakis, Alexandros; Charalabopoulos, Alexandros; Tsolakidis, Alexandros; Chirca, Alexandru; Arnaud, Alexis P; Narvaez-Rojas, Alexis Rafael; Kavalakat, Alfie; Spina, Alfio; Recordare, Alfonso; Annicchiarico, Alfredo; Conti, Alfredo; Mohammed, Alhassan Datti; Kocataş, Ali; Almhimid, Ali; Arnaout, Ali; Fahmy, Ali; Mangi, Ali; Modabber, Ali; Ulas, Ali Bilal; Mohamedahmed, Ali Yasen Y; Frontali, Alice; Moynihan, Alice; Yunus, Alif; Ahmad, Aline;

Background: Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods: This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low-middle-income countries. Results: In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of 'single-use' consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low-middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion: This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high- and low-middle-income countries.

2023 - Refinement of the diagnostic approach for the identification of children and adolescents affected by familial hypercholesterolemia: Evidence from the LIPIGEN study [Articolo su rivista]
Casula, M.; Gazzotti, M.; Capra, M. E.; Olmastroni, E.; Galimberti, F.; Catapano, A. L.; Pederiva, C.; Anesi, A.; Arca, M.; Auricchio, R.; Averna, M.; Baldera, D.; Banderali, G.; Beccuti, G.; Benso, A.; Berteotti, M.; Bertolini, S.; Bianconi, V.; Biasucci, G.; Biolo, G.; Bonanni, L.; Borghi, C.; Bossi, A. C.; Branchi, A.; Bruzzi, P.; Bucci, M.; Buonuomo, P. S.; Calabro, P.; Calandra, S.; Carubbi, F.; Cavallaro, R.; Cefalu, A. B.; Cesaro, A.; Cipollone, F.; Citroni, N.; Colombo, E.; Coppola, C.; D'Addato, S.; Dal Pino, B.; Dalla Nora, E.; De Corrado, G.; Del Ben, M.; Di Molfetta, S.; Di Taranto, M. D.; Fainelli, G.; Federici, M.; Ferri, C.; Fiorenza, A. M.; Formisano, E.; Fortunato, G.; Giaccari, A.; Giorgino, F.; Grigore, L.; Guardamagna, O.; Iannuzzi, A.; Iannuzzo, G.; Iughetti, L.; Lia, S.; Longo, S.; Lupi, A.; Mandraffino, G.; Marcucci, R.; Maroni, L.; Massini, G.; Mazza, E.; Melchioda, E.; Meregalli, G.; Minicocci, I.; Moffa, S.; Mombelli, G.; Muntoni, S.; Nascimbeni, F.; Negri, E. A.; Notargiacomo, S.; Panfili, F. M.; Parati, G.; Passaro, A.; Pavanello, C.; Pecchioli, V.; Pecchioli, L.; Pellegatta, F.; Perla, F. M.; Pipolo, A.; Piro, S.; Pirro, M.; Pisciotta, L.; Pujia, R.; Putotto, C.; Repetti, E.; Rinaldi, E.; Romandini, A.; Sani, E.; Sarnari, S.; Sarzani, R.; Sbrana, F.; Scicali, R.; Scuruchi, M.; Suppressa, P.; Tarugi, P.; Trenti, C.; Vinci, P.; Werba, J. P.; Zambon, S.; Zambon, A.; Zenti, M. G.

Background and aims: We aimed to describe the limitations of familiar hypercholesterolemia (FH) diagnosis in childhood based on the presence of the typical features of FH, such as physical sings of cholesterol accumulation and personal or family history of premature cardiovascular disease or hypercholesterolemia, comparing their prevalence in the adult and paediatric FH population, and to illustrate how additional information can lead to a more effective diagnosis of FH at a younger age. Methods: From the Italian LIPIGEN cohort, we selected 1188 (≥18 years) and 708 (<18 years) genetically-confirmed heterozygous FH, with no missing personal FH features. The prevalence of personal and familial FH features was compared between the two groups. For a sub-group of the paediatric cohort (N = 374), data about premature coronary heart disease (CHD) in second-degree family members were also included in the evaluation. Results: The lower prevalence of typical FH features in children/adolescents vs adults was confirmed: the prevalence of tendon xanthoma was 2.1% vs 13.1%, and arcus cornealis was present in 1.6% vs 11.2% of the cohorts, respectively. No children presented clinical history of premature CHD or cerebral/peripheral vascular disease compared to 8.8% and 5.6% of adults, respectively. The prevalence of premature CHD in first-degree relatives was significantly higher in adults compared to children/adolescents (38.9% vs 19.7%). In the sub-cohort analysis, a premature CHD event in parents was reported in 63 out of 374 subjects (16.8%), but the percentage increased to 54.0% extending the evaluation also to second-degree relatives. Conclusions: In children, the typical FH features are clearly less informative than in adults. A more thorough data collection, adding information about second-degree relatives, could improve the diagnosis of FH at younger age.

2023 - Surgery for Port-Wine Stains: A Systematic Review [Articolo su rivista]
Colletti, G.; Negrello, S.; Rozell-Shannon, L.; Levitin, G. M.; Colletti, L.; Chiarini, L.; Anesi, A.; Di Bartolomeo, M.; Pellacani, A.; Nocini, R.

Background: Port-wine stains (PWS) are congenital low-flow vascular malformations of the skin. PWS tend to become thicker and darker with time. Laser therapy is the gold standard and the first-line therapy for treating PWS. However, some resistant PWS, or PWS that have tissue hypertrophy, do not respond to this therapy. Our aim is to evaluate the role of surgery in the treatment of PWS birthmarks. Methods: A literature search was performed in PubMed, Scopus, Web of Science (WOS) and Google Scholar for all papers dealing with surgery for port-wine stains, from January 2010 to December 2020 using the search strings: (capillary vascular malformation OR port-wine stains OR Sturge Weber Syndrome OR sws OR pws) AND (surgical OR surgery). Results: Ten articles were identified and used for analysis. They were almost all case series with a short follow up period and lacked an objective–systematic score of evaluation. Conclusions: Delay in treatment of port wine stains may result in soft tissue and bone hypertrophy or nodules with disfiguring or destructive characteristics. The correction of PWS-related facial asymmetry often requires bone surgery followed by soft tissue corrections to achieve a more harmonious, predictable result.

2023 - The Capacity of Magnesium to Induce Osteoclast Differentiation Is Greatly Enhanced by the Presence of Zoledronate [Articolo su rivista]
Ricchiuto, Silvia; Palumbo, Rossella; Lami, Francesca; Gavioli, Francesca; Caselli, Lorenzo; Montanari, Monica; Zappavigna, Vincenzo; Anesi, Alexandre; Zanocco-Marani, Tommaso; Grande, Alexis

Simple Summary A number of skeletal disorders, all characterized by a metabolic or neoplastic loss of bone tissue, are cured with drugs called Bisphosphonates (BPs), which exert their therapeutic effect by suppressing cells named osteoclasts, normally mediating bone resorption. Unfortunately, these drugs can also provoke a dangerous side effect known as osteonecrosis of the jaw (ONJ), a bone infection localized in the oral cavity and characterized by gingival ulceration, sometimes accompanied by suppuration and pain. This condition, occasionally arising spontaneously, is more often started by a tooth extraction. The reduced number of osteoclasts, determined by BPs, is thought to favor the bacterial invasion of healthy bone and the incapacity to eliminate infected bone, that are in turn responsible for the appearance of ONJ. Here we show that Magnesium, used for decades as dietary supplement, can invert the effect of BPs, transforming them, through a sort of paradox effect, into powerful activators of osteoclast production. These results suggest that Magnesium might be used in a topical approach aimed to cure or prevent ONJ. Notably, the capacity of Magnesium to activate osteoclast production was even observed in absence of BPs, suggesting its application also in ONJ forms caused by agents distinct to BPs.Abstract Bisphosphonates (BPs) are successfully used to cure a number of diseases characterized by a metabolic reduction in bone density, such as Osteoporosis, or a neoplastic destruction of bone tissue, such as multiple myeloma and bone metastases. These drugs exert their therapeutic effect by causing a systemic osteoclast depletion that, in turn, is responsible for reduced bone resorption. Unfortunately, in addition to their beneficial activity, BPs can also determine a frightening side effect known as osteonecrosis of the jaw (ONJ). It is generally believed that the inability of osteoclasts to dispose of inflamed/necrotic bone represents the main physiopathological aspect of ONJ. In principle, a therapeutic strategy able to elicit a local re-activation of osteoclast production could counteract ONJ and promote the healing of its lesions. Using an experimental model of Vitamin D3-dependent osteoclastogenesis, we have previously demonstrated that Magnesium is a powerful inducer of osteoclast differentiation. Here we show that, surprisingly, this effect is greatly enhanced by the presence of Zoledronate, chosen for our study because it is the most effective and dangerous of the BPs. This finding allows us to hypothesize that Magnesium might play an important role in the topical therapy of ONJ.

2022 - Ameloblastoma in a Three-Year-Old Child with Hurler Syndrome (Mucopolysaccharidosis Type I) [Articolo su rivista]
Di Bartolomeo, Mattia; Pellacani, Arrigo; Negrello, Sara; Buchignani, Martina; Nocini, Riccardo; Di Massa, Gianluca; Gianotti, Greta; Pollastri, Giuseppe; Colletti, Giacomo; Chiarini, Luigi; Anesi, Alexandre

2022 - Deep Segmentation of the Mandibular Canal: a New 3D Annotated Dataset of CBCT Volumes [Articolo su rivista]
Cipriano, Marco; Allegretti, Stefano; Bolelli, Federico; Di Bartolomeo, Mattia; Pollastri, Federico; Pellacani, Arrigo; Minafra, Paolo; Anesi, Alexandre; Grana, Costantino

Inferior Alveolar Nerve (IAN) canal detection has been the focus of multiple recent works in dentistry and maxillofacial imaging. Deep learning-based techniques have reached interesting results in this research field, although the small size of 3D maxillofacial datasets has strongly limited the performance of these algorithms. Researchers have been forced to build their own private datasets, thus precluding any opportunity for reproducing results and fairly comparing proposals. This work describes a novel, large, and publicly available mandibular Cone Beam Computed Tomography (CBCT) dataset, with 2D and 3D manual annotations, provided by expert clinicians. Leveraging this dataset and employing deep learning techniques, we are able to improve the state of the art on the 3D mandibular canal segmentation. The source code which allows to exactly reproduce all the reported experiments is released as an open-source project, along with this article.

2022 - Editorial for the Special Issue on “Multidisciplinary Insights on Bone Healing” [Articolo su rivista]
Anesi, A.; Cavani, F.

: Animal and human bone damage can be considered differently according to a macro- or micro-level analysis [...].

2022 - Elective surgery system strengthening: development, measurement, and validation of the surgical preparedness index across 1632 hospitals in 119 countries [Articolo su rivista]
Glasbey, Jc; Abbott, Tef; Ademuyiwa, A; Adisa, A; Alameer, E; Alshryda, S; Arnaud, Ap; Bankhead-Kendall, B; Abou Chaar, Mk; Chaudhry, D; Costas-Chavarri, A; Cunha, Mf; Davies, Ji; Desai, A; Elhadi, M; Fiore, M; Fitzgerald, Je; Fourtounas, M; Fowler, Aj; Futaba, K; Gallo, G; Ghosh, D; Gujjuri, Rr; Hamilton, R; Haque, P; Harrison, Em; Anesi, A; Hutchinson, P; Hyman, G; Isik, A; Jayarajah, U; Kaafarani, Hma; Kadir, B; Lawani, I; Lederhuber, H; Li, E; Loffler, Mw; Lorena, Ma; Mann, H; Martin, J; Mazingi, D; Mcclain, Cd; Mclean, Ka; Meara, Jg; Ramos-De La Medina, A; Mengesha, M; Minaya, A; Modolo, Mm; Moore, R; Morton, D; Nepogodiev, D; Ntirenganya, F; Pata, F; Pearse, R; Picciochi, M; Pinkney, T; Pockney, P; van Ramshorst, Gh; Richards, T; Roslani, Ac; Satoi, S; Sayyed, R; Shaw, R; Simoes, Jff; Smart, N; Sulliva, R; Sund, M; Sundar, S; Tabiri, S; Taylor, Eh; Venn, Ml; Wickramasinghe, D; Wright, N; Yip, Sbs; Bhangu, A

Background The 2015 lancet Commission on global surgery identified surgery and anaesthesia as indispensable parts of holistic health-care systems. However, COVID-19 exposed the fragility of planned surgical services around the world, which have also been neglected in pandemic recovery planning. This study aimed to develop and validate a novel index to support local elective surgical system strengthening and address growing backlogs.Methods First, we performed an international consultation through a four-stage consensus process to develop a multidomain index for hospital-level assessment (surgical preparedness index; SPI). Second, we measured surgical preparedness across a global network of hospitals in high-income countries (HICs), middle-income countries (MICs), and low-income countries (LICs) to explore the distribution of the SPI at national, subnational, and hospital levels. Finally, using COVID-19 as an example of an external system shock, we compared hospitals' SPI to their planned surgical volume ratio (SVR; ie, operations for which the decision for surgery was made before hospital admission), calculated as the ratio of the observed surgical volume over a 1-month assessment period between June 6 and Aug 5,2021, against the expected surgical volume based on hospital administrative data from the same period in 2019 (ie, a pre-pandemic baseline). A linear mixed-effects regression model was used to determine the effect of increasing SPI score.Findings In the first phase, from a longlist of 103 candidate indicators, 23 were prioritised as core indicators of elective surgical system preparedness by 69 dinicians (23133%) women; 46 [67%] men; 41 from HICs, 22 from MICs, and six from LICs) from 32 countries. The multidomain SPI included 11 indicators on facilities and consumables, two on staffing, two on prioritisation, and eight on systems. Hospitals were scored from 23 (least prepared) to 115 points (most prepared). In the second phase, surgical preparedness was measured in 1632 hospitals by 4714 clinicians from 119 countries. 745 (45.6%) of 1632 hospitals were in MICs or LICs. The mean SPI score was 84.5 (95% CI 84.1-84.9), which varied between HIC (88.5 189.0-88.0]), MIC (81.8 [82.5-81.1]), and LIC (66.8 [64.9-68.7]) settings. In the third phase, 1217 (74.6%) hospitals did not maintain their expected SVR during the COVID-19 pandemic, of which 625 (51.4%) were from HIC, 538 (44.2%) from MIC, and 54 (4.4%) from LIC settings. In the mixed-effects model, a 10-point increase in SPI corresponded to a 3.6% (95% CI 3.0-4.1; p<0.0001) increase in SVR. This was consistent in HIC (4.8% [4.1-5.5]; p<0.0001), MIC (2.8 [2.0-3.7]; p<0.0001), and LIC (3.8 [1.3-6 . 7%]; p<0.0001) settings.Interpretation The SPI contains 23 indicators that are globally applicable, relevant across different system stressors, vary at a subnational level, and are collectable by front-line teams. In the case study of COVID-19, a higher SPI was associated with an increased planned surgical volume ratio independent of country income status, COVID-19 burden, and hospital type. Hospitals should perform annual self-assessment of their surgical preparedness to identify areas that can be improved, create resilience in local surgical systems, and upscale capacity to address elective surgery backlogs. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.

2022 - Pulsed Electro-Magnetic Field (PEMF) Effect on Bone Healing in Animal Models: A Review of Its Efficacy Related to Different Type of Damage [Articolo su rivista]
Di Bartolomeo, M.; Cavani, F.; Pellacani, A.; Grande, A.; Salvatori, R.; Chiarini, L.; Nocini, R.; Anesi, A.

Biophysical energies are a versatile tool to stimulate tissues by generating biopotentials. In particular, pulsed electromagnetic field (PEMF) stimulation has intrigued researchers since the 1970s. To date, many investigations have been carried out in vivo, but a gold standard treatment protocol has not yet been defined. The main obstacles are represented by the complex setting of PEMF characteristics, the variety of animal models (including direct and indirect bone damage) and the lack of a complete understanding of the molecular pathways involved. In the present review the main studies about PEMF stimulation in animal models with bone impairment were reviewed. PEMF signal characteristics were investigated, as well as their effect on molecular pathways and osseous morphological features. We believe that this review might be a useful starting point for a prospective study in a clinical setting. Consistent evidence from the literature suggests a potential beneficial role of PEMF in clinical practice. Nevertheless, the wide variability of selected parameters (frequency, duration, and amplitude) and the heterogeneity of applied protocols make it difficult to draw certain conclusions about PEMF effectiveness in clinical implementation to promote bone healing. Deepening the knowledge regarding the most consistent results reported in literature to date, we believe that this review may be a useful starting point to propose standardized experimental guidelines. This might provide a solid base for further controlled trials, to investigate PEMF efficacy in bone damage conditions during routine clinical practice.

2022 - The vanishing port-wine stain birthmark—consideration for a rare type of congenital vascular anomaly [Articolo su rivista]
Pellacani, Arrigo; Rozell-Shannon, Linda; Negrello, Sara; Di Bartolomeo, Mattia; Anesi, Alexandre; Feminò, Raimondo; Mariotti, Ilaria; Chiarini, Luigi; Colletti, Giacomo

2022 - Tongue cancer following hematopoietic cell transplantation for Fanconi anemia [Articolo su rivista]
Di Bartolomeo, Mattia; Anesi, Alexandre; Pellacani, Arrigo; Negrello, Sara; Natale, Annalisa; Figurelli, Sabina; Vaddinelli, Doriana; Angelini, Stefano; Chiarini, Luigi; Nocini, Riccardo; Di Bartolomeo, Paolo

Objectives: The aim of this retrospective study was to determine the incidence and the clinical outcome of tongue cancer (TC) in patients affected by Fanconi anemia (FA) who received an allogeneic hematopoietic cell transplantation (HCT). Materials and methods: The patient database from the Bone Marrow Transplant Center of Pescara was reviewed to enroll FA patients. Patients', donors', HCT's, and screening's data were collected as well to look for the incidence and the treatment of TC. Results: Twelve patients affected by FA were identified. Three patients died for transplant-related causes. Five of nine surviving patients were diagnosed with TC at a median of 21.7 years since transplantation and at a median age of 32.10 years. Interestingly, no patient manifested graft-versus-host-disease (GvHD). The 28-year cumulative incidence function of TC was 46.9% (95% CI, 36.9-56.9%). Two patients were treated with chemotherapy alone, two patients were treated with surgery alone, and one with surgery followed by chemotherapy. Overall, 4 patients with TC showed a clinical course characterized by a marked aggressiveness of the tumor disease which led to death due to cancer progression between 2 and 13 months. One patient is surviving 8 months after diagnosis of TC. Conclusions: Our study confirms the high incidence of tumors and in particular tongue tumors in allotransplanted FA patients. A careful screening has to be life-long maintained. Clinical relevance: Considering the rarity of FA and the frailty of FA patients, this study may add important information for the cancer management of these patients.

2021 - A Case Report of a Solitary Fibrous Tumor of the Maxillary Sinus [Articolo su rivista]
Di Bartolomeo, Mattia; Negrello, Sara; Pellacani, Arrigo; Cesinaro, Anna Maria; Vallone, Stefano; Presutti, Livio; Chiarini, Luigi; Anesi, Alexandre

A solitary fibrous tumor (SFT) is a benign neoplasm, firstly described as a mesenchymal tumor of the pleura. Its incidence range in the head and neck region is about 5–27%, but only rarely does it affect paranasal sinuses. The differential diagnosis is challenging, owing to its erosive growth pattern and immuno-histochemical features. SFTs have an aggressive behavior and an important recurrence potential. Therefore, a radical surgical excision is the gold standard therapeutic procedure. A rare SFT originating from the right maxillary sinus is reported here. The 37-year-old patient presented to the outpatient clinic with a painful expansive lesion in the whole right maxillary region. The overlying skin was inflamed and the patient had no epistaxis episodes. The 1.5 dentary element tested negative for vitality; however, a puncture of the lesion led to a hematic spill and no purulent discharge. An endoscopic-guided biopsy was suggestive either of SFT or hemangioperictoma, excluding a malignant neoplasm. A multi-equipe surgical team was activated. The lesion was embolized in order to achieve a good hemostatic control and, after 48 h, the neoplasm was radically excised with a combined open and endoscopic approach. The patient was disease-free at 12-month radiological and clinical follow-up. Given the rarity of this lesion and the delicacy required in addressing head and neck neoplasms, we believe that the present case report might be of help in further understanding how to approach cranio-facial SFTs.

2021 - A Cone Beam Computed Tomography Annotation Tool for Automatic Detection of the Inferior Alveolar Nerve Canal [Relazione in Atti di Convegno]
Mercadante, Cristian; Cipriano, Marco; Bolelli, Federico; Pollastri, Federico; Di Bartolomeo, Mattia; Anesi, Alexandre; Grana, Costantino

In recent years, deep learning has been employed in several medical fields, achieving impressive results. Unfortunately, these algorithms require a huge amount of annotated data to ensure the correct learning process. When dealing with medical imaging, collecting and annotating data can be cumbersome and expensive. This is mainly related to the nature of data, often three-dimensional, and to the need for well-trained expert technicians. In maxillofacial imagery, recent works have been focused on the detection of the Inferior Alveolar Nerve (IAN), since its position is of great relevance for avoiding severe injuries during surgery operations such as third molar extraction or implant installation. In this work, we introduce a novel tool for analyzing and labeling the alveolar nerve from Cone Beam Computed Tomography (CBCT) 3D volumes.

2021 - Magnesium favors the capacity of vitamin d3 to induce the monocyte differentiation of u937 cells [Articolo su rivista]
Parenti, S.; Sandoni, L.; Montanari, M.; Zanocco-Marani, T.; Anesi, A.; Iotti, S.; Manfredini, R.; Frassineti, C.; Davalli, P.; Grande, A.

The hematopoietic U937 cells are able to differentiate into monocytes, macrophages, or osteoclasts when stimulated, respectively, with vitamin D3 (VD3), phorbol 12-myristate 13-acetate (PMA) or PMA plus VD3. We have previously demonstrated that magnesium (Mg) strongly potentiates the osteoclastic differentiation of U937 cells. In this study, we investigated whether such an effect may be ascribed to a capacity of Mg to modulate the monocyte differentiation of U937 cells and/or to an ability of Mg and VD3 to act directly and independently on the early phases of the osteoclastic differentiation. To address this issue, we subjected U937 cells to an individual and combined treatment with Mg and VD3 and then we analyzed, by flow cytometry and quantitative real-time polymerase chain reaction, the expression of a number of genes related to the early phases of the differentiation pathways under consideration. The results obtained indicated that Mg favors the monocyte differentiation of U937 cells induced by VD3 and at the same time, Mg contrasts the inhibitory effect that VD3 exerts on the osteoclastic differentiation in the absence of PMA. The crucial and articulated role played by Mg in diverse pathways of the osteoclastic differentiation of U973 cells is emphasized.

2020 - A Novel Bioactive Glass Containing Therapeutic Ions with Enhanced Biocompatibility [Articolo su rivista]
Sergi, Rachele; Bellucci, Devis; Salvatori, Roberta; Anesi, Alexandre; Cannillo, Valeria

2020 - Bone Healing Evaluation Following Different Osteotomic Techniques in Animal Models: A Suitable Method for Clinical Insights [Articolo su rivista]
Anesi, Alexandre; Di Bartolomeo, Mattia; Pellacani, Arrigo; Ferretti, Marzia; Cavani, Francesco; Salvatori, Roberta; Nocini, Riccardo; Palumbo, Carla; Chiarini, Luigi

Osteotomy is a common step in oncological, reconstructive, and trauma surgery. Drilling and elevated temperature during osteotomy produce thermal osteonecrosis. Heat and associated mechanical damage during osteotomy can impair bone healing, with consequent failure of fracture fixation or dental implants. Several ex vivo studies on animal bone were recently focused on heating production during osteotomy with conventional drill and piezoelectric devices, particularly in endosseous dental implant sites. The current literature on bone drilling and osteotomic surface analysis is here reviewed and the dynamics of bone healing after osteotomy with traditional and piezoelectric devices are discussed. Moreover, the methodologies involved in the experimental osteotomy and clinical studies are compared, focusing on ex vivo and in vivo findings.

2020 - Cell Proliferation to Evaluate Preliminarily the Presence of Enduring Self-Regenerative Antioxidant Activity in Cerium Doped Bioactive Glasses [Articolo su rivista]
Anesi, Alexandre; Malavasi, Gianluca; Chiarini, Luigi; Salvatori, Roberta; Lusvardi, Gigliola

(1) Background: a cell evaluation focused to verify the self-regenerative antioxidant activity is performed on cerium doped bioactive glasses. (2) Methods: the glasses based on 45S5 Bioglass®, are doped with 1.2 mol%, 3.6 mol% and 5.3 mol% of CeO2 and possess a polyhedral shape (~500 µm2). Glasses with this composition inhibit oxidative stress by mimicking catalase enzyme (CAT) and superoxide dismutase (SOD) activities; moreover, our previous cytocompatibility tests (neutral red (NR), 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Bromo-2-deoxyUridine (BrdU)) reveal that the presence of cerium promotes the absorption and vitality of the cells. The same cytocompatibility tests were performed and repeated, in two different periods (named first and second use), separated from each other by four months. (3) Results: in the first and second use, NR tests indicate that the presence of cerium promotes once again cell uptake and viability, especially after 72 h. A decrease in cell proliferation it is observed after MTT and BrdU tests only in the second use. These findings are supported by statistically significant results (4) Conclusions: these glasses show enhanced proliferation, both in the short and in the long term, and for the first time such large dimensions are studied for this kind of study. A future prospective is the implantation of these bioactive glasses as bone substitute in animal models.

2020 - Emerging challenges and possible strategies in maxillo-facial and oral surgery during the COVID-19 pandemic [Articolo su rivista]
Di Bartolomeo, Mattia; Pellacani, Arrigo; Negrello, Sara; Chiarini, Luigi; Anesi, Alexandre

The Coronavirus disease 2019 (COVID-19) pandemic suddenly took the world by storm and Italy was one of the hardest hit countries. Maxillo-facial surgery and dentistry procedures had to be significantly reorganized, since they are considered high-risk procedures. Protocols had to be changed and interdepartmental cooperation was put in place to plan surgical interventions and maintain high standards. Various improvements have been made to prevent and reduce the risks of spreading the infection. Even if the situation seems to have improved, being unprepared is not an option. In this paper the experience gained during these months has been shared and possible future challenges has been highlighted, suggesting practical adjustments based also on new guidelines and recommendations.

2020 - Primary Intraosseous Squamous Cell Carcinoma of the Anterior Mandible Arising in an Odontogenic Cyst in 34-Year-Old Male [Articolo su rivista]
Negrello, Sara; Pellacani, Arrigo; di Bartolomeo, Mattia; Bernardelli, Giuditta; Nocini, Riccardo; Pinelli, Massimo; Chiarini, Luigi; Anesi, Alexandre

2020 - Variations in concerns reported on the patient concerns inventory in patients with head and neck cancer from different health settings across the world [Articolo su rivista]
Rogers, Simon N; Alvear, Alvaro; Anesi, Alexandre; Babin, Emmanuel; Balik, Ali; Batstone, Martin; Brockmeyer, Phillipp; Carrasco, Claudia Celedon; Chien, Chih-Yen; Chirila, Magdalena; Dholam, Kanchan P; Doss, Jennifer G; Finizia, Caterina; Ghani, Wan M Nabilah; Gurav, Sandeep V; Kadir, Kathreena; Kolator, Mateusz; Lima, Roberto; Lin, Yu-Tsai; Nhongo, Simon; Ozdemir-Karatas, Meltem; Peker, Kadriye; Pesic, Zoran; Ransy, Pierre; Santos, Izabella; Schliephake, Henning; Shah, Ketan; Souza, Fernanda; Sunil, Geethu; Thankappan, Krishnakumar; Ehrsson, Ylva Tiblom; Tiple, Cristina; Tuomi, Lisa; Valerini, Sara; Lara, Pablo Vasquez; Zatoński, Tomasz; Lowe, Derek

Background The aim was to collate and contrast patient concerns from a range of different head and neck cancer follow-up clinics around the world. Also, we sought to explore the relationship, if any, between responses to the patient concerns inventory (PCI) and overall quality of life (QOL). Methods Nineteen units participated with intention of including 100 patients per site as close to a consecutive series as possible in order to minimize selection bias. Results There were 2136 patients with a median total number of PCI items selected of 5 (2-10). "Fear of the cancer returning" (39%) and "dry mouth" (37%) were most common. Twenty-five percent (524) reported less than good QOL. Conclusion There was considerable variation between units in the number of items selected and in overall QOL, even after allowing for case-mix variables. There was a strong progressive association between the number of PCI items and QOL.

2019 - A new bioactive glass/collagen hybrid composite for applications in dentistry [Articolo su rivista]
Bellucci, D.; Salvatori, R.; Giannatiempo, J.; Anesi, A.; Bortolini, S.; Cannillo, V.

Bioactive glasses (BGs) are currently employed in a wide range of medical and dentistry applications by virtue of their bone-bonding ability. The incorporation of BGs into a collagen matrix may be used to combine the regenerative potential of these materials with the specific biological advantages of collagen. However, most of the collagen/BG composites reported in the literature are scaffolds and there is a lack of moldable putties or injectable systems. Here, granules of an innovative BG containing strontium and magnesium were mixed with collagen and PEG to obtain a putty (BGMS/C) suitable for dental applications. For the sake of comparison, granules of 45S5 Bioglass®, the gold standard among BGs, were used to prepare a 45S5/collagen putty. Both the composites were evaluated in vitro with respect to murine fibroblasts. The materials showed an excellent biocompatibility, making them interesting for possible applications in dentistry and reconstructive surgery. Moreover, BGMS/C seems to stimulate cell proliferation.

2019 - Assessment [Capitolo/Saggio]
Anesi, Alexandre; Negrello, Sara; Chiarini, Luigi

In order to achieve an adequate oral rehabilitation after reconstruction of the jaw, a consistent prosthetic treatment is necessary. The main determinants of implant stability are the mechanical properties of the bone tissue at the implant site, and how the contact between the implant neck and the cortical bone plate is achieved. If we presume a correct surgical technique and a good implant design, the bone density determines the primary implant stability at the time of surgery. A stable implant can exhibit different degrees of displacement or resistance to load, which corresponds to varying degrees of stability. Conversely, a failed implant shows clinical mobility on the macroscale, as the implant is surrounded by a fibrous scar tissue. An increasing degree of micro-mobility is present until clinical failure of the implant. This suggests that techniques to measure and to monitor implant micro-motion/stability could give the clinician the opportunity to optimize implant treatment. Insertion torque, Periotest, and resonance frequency analysis are suitable to measure primary implant stability. Nevertheless, the resonance frequency analysis is the only method that can detect variations in different bone densities, which may be measured even during the follow-up of the implant.

2019 - Bone Augmentation [Capitolo/Saggio]
Nocini, Pier Francesco; Anesi, Alexandre; Fior, Andrea

The main limitation of the free fibula flap reconstruction is bone height that is insufficient for restoring both the skeletal base and the alveolar ridge. This is especially evident when the native mandible is dentate at the unaffected site adjacent to fibula flap. In implant-borne dental rehabilitation, if the reconstructed alveolar ridge is low, we may get an inadequate crown-to-implant ratio. To overcome the high discrepancy between the reconstructed alveolar crest and the native one, some therapeutic options have been introduced: fixation of the fibula at the level of the residual alveolar crest of the healthy side, primary use of the fibula as a double-barrel graft, delayed onlay bone graft on the fibula, later vertical distraction osteogenesis and secondary osteotomies to correct malocclusion after fibula. Techniques for vertical bone augmentation in fibula flap are here discussed.

2019 - Clinical Management of Acinic Cell Carcinoma of the Lacrimal Gland [Articolo su rivista]
Anesi, A.; Negrello, S.; Lucchetti, D.; Pollastri, G.; Trevisiol, L.; Badiali, L.; Lazzerini, A.; Cavallini, G. M.; Chiarini, L.

To report a case of acinic cell carcinoma occurred in the lacrimal gland. A 59-year-old man was admitted because of sudden blurring of vision, progressive proptosis of the left eye, and mild double vision in left and down directions of the gaze (Hess-Lancaster test). His medical history detailed controlled bilateral keratoconus and open angle glaucoma. On examination, the best corrected visual acuity decreased from 8/20 till 1/50 in one week. There was a swelling of the left upper eyelid. A hard and tender mass was palpated in the superior temporal left orbit. Ultrasound scan showed an extraconal solid mass, situated in the superior lateral corner of the orbit. Computed tomography and magnetic resonance imaging (MRI) revealed a mass of two centimeters in diameter, with round well-defined outline, within the lacrimal gland. We per-formed an enucleoresection of the mass, via a coronal approach and a lateral orbitotomy by a piezosurgical device. The lesion appeared nodular, brownish, measuring about 2 × 1.5 cm. Histopathological findings were consistent with acinic cell carcinoma with a microcystic, focally papillary-cystic growth of pattern. Follow-up MRI outcomes led to removal of the residual lacrimal gland for suspicion of recurrence. No tumor recurrences where detected at 7-year follow-up.

2019 - Cytocompatibility of potential bioactive cerium-doped glasses based on 45S5 [Articolo su rivista]
Malavasi, Gianluca; Salvatori, Roberta; Zambon, Alfonso; Lusvardi, Gigliola; Rigamonti, Luca; Chiarini, Luigi; Anesi, Alexandre

The cytocompatibility of potential bioactive cerium-containing (Ce 3+ /Ce 4+ ) glasses is here investigated by preparing three different glasses with increasing amount of doping CeO 2 (1.2, 3.6 and 5.3 mol% of CeO 2 , called BG_1.2, BG_3.6 and BG_5.3, respectively) based on 45S5 Bioglass®(called BG). These materials were characterized by Environmental Scanning Electron Microscopy (ESEM) and infrared spectroscopy (FTIR) after performing bioactivity tests in Dulbecco's Modified Eagle Medium (DMEM) solution, and the ions released in solution were determined by Inductively Coupled Plasma Mass Spectrometry (ICP-MS) and Optical Emission Spectrometry (ICP-OES). The data obtained clearly show that the glass surfaces of BG, BG_1.2 and BG_3.6 were covered by hydroxyapatite (HA), while BG_5.3 favored the formation of a cerium phosphate crystal phase. The cytotoxicity tests were performed using both murine long bone osteocyte-like (MLO-Y4) and mouse embryonic fibroblast (NIH/3T3) cell lines. The cerium-containing bioactive glasses show an increment in cell viability with respect to BG, and at long times, no cell aggregation and deformation were observed. The proliferation of NIH/3T3 cells increased with the cerium content in the glasses; in particular, BG_3.6 and BG_5.3 showed a higher proliferation of cells than the negative control. These results highlight and enforce the proposal of cerium-doped bioactive glasses as a new class of biomaterials for hard-tissue applications.

2019 - Evolution in Bone Synthesis [Capitolo/Saggio]
Fior, Andrea; Anesi, Alexandre; Nocini, Pier Francesco

The difficulty with the fixation method in jaws reconstruction with fibula flap is related to the number of osteotomies required and the length of the bone segments needed. The larger the defect in the jaw, the more osteotomies are necessary, and the more complex the procedure becomes. Length and angle of the bone segments have a direct effect on their position, which affect the final facial bone contour. Generally speaking, fixation techniques can be divided into rigid and nonrigid forms of fixation. Nonrigid fixation uses interosseous wire fixation, wire mesh fixation, overlay and onlay bone grafting, titanium tray fixation, and Kirschner wire fixation. Studies have not been able to demonstrate any difference in the rate of bone healing between the rigid and nonrigid fixation methods in mandibular reconstruction. Nevertheless, nonrigid fixation methods are rarely used in today’s clinical practice, because they prove to be laborious. Rigid fixation methods use lag screw fixation, staples, titanium tray fixation, external fixation appliances, miniplates, and diverse reconstruction plates. Locking mandibular reconstruction plate is one of the most important technological advances in mandibular fixation: it becomes unnecessary for the plate to intimately contact the underlying bone in all areas, thus avoiding compression of periosteal blood perfusion of the underlying cortical bone. Following the Hidalgo experience (1989), in the early 2000s the use of miniplates as opposed to reconstruction plates (lower profiles and smaller screw diameters) has been the subject of intense debate. Custom-made pre-bent reconstruction plates are the most recent and the final step of the virtual design process. Only custom reconstruction pre-bent plates prove to be superior to miniplates or to modern reconstruction plates. Adding cost and different health economies limit worldwide accessibility and diffusion of this technology innovation.

2019 - Evolution in Indication [Capitolo/Saggio]
Anesi, Alexandre; Negrello, Sara; Chiarini, Luigi

Since the introduction of reconstructive technique using the fibula flap, the indications for use of this graft have evolved. The fibula graft may provide skin islands, up to 25 cm and 14 cm wide, suitable for reconstruction of associated soft tissue defects. The dual endosteal and periosteal blood supply ensures bony viability despite multiple osteotomies. Hidalgo in 1989 described the first lower jaw reconstruction with a fibular flap, using osteotomies to mimic the shape of the mandible after oncological or traumatic defects. Multiple skin islands can be harvested with the fibula graft providing an osteomyocutaneous flap, including those based on septocutaneous as well as on musculocutaneous peroneal perforators. This graft provides convenient tissue for simultaneous reconstruction of bony and soft tissue defects inside as well as outside the oral cavity, bringing viable tissue to a mostly irradiated and contaminated field, with the lowest complication rate among osteocutaneous flaps. Soleus muscle connected to motor branches at the recipient site is described to restore the motor function or by using the sural cutaneous nerve together with a skin island for restoring sensation. Flap combinations were performed by anastomosing a second free flap to the distal peroneal artery and vein, which do not significantly reduce in caliber and thus can also serve at the recipient site. The use of free vascularized fibula has become the gold standard for mandibular and maxillary extensive defects.

2019 - From Osteoclast Differentiation to Osteonecrosis of the Jaw: Molecular and Clinical Insights [Articolo su rivista]
Anesi, Alexandre; Generali, Luigi; Sandoni, Laura; Pozzi, Samantha; Grande, Alexis

Bone physiology relies on the delicate balance between resorption and formation of its tissue. Bone resorption depends on a process called osteoclastogenesis in which bone-resorbing cells, i.e., osteoclasts, are produced by the differentiation of more undifferentiated progenitors and precursors. This process is governed by two main factors, monocyte colony-stimulating factor (M-CSF) and receptor activator of NFκB ligand (RANKL). While the former exerts a proliferating effect on progenitors/precursors, the latter triggers a differentiation effect on more mature cells of the same lineage. Bone homeostasis requires a perfect space–time coordination of the involved signals. When osteoclastogenesis is poorly balanced with the differentiation of the bone forming counterparts, i.e., osteoblasts, physiological bone remodelling can turn into a pathological state, causing the systematic disruption of bone tissue which results in osteopenia or osteolysis. Examples of these conditions are represented by osteoporosis, Paget’s disease, bone metastasis, and multiple myeloma. Therefore, drugs targeting osteoclastogenesis, such as bisphosphonates and an anti-RANKL monoclonal antibody, have been developed and are currently used in the treatment of such diseases. Despite their demonstrated therapeutic efficacy, these agents are unfortunately not devoid of side effects. In this regard, a condition called osteonecrosis of the jaw (ONJ) has been recently correlated with anti-resorptive therapy. In this review we will address the involvement of osteoclasts and osteoclast-related factors in the pathogenesis of ONJ. It is to be hoped that a better understanding of the biological mechanisms underlying bone remodelling will help in the design a medical therapeutic approach for ONJ as an alternative to surgical procedures.

2019 - Lateral, Hemimandibular, Anterior. [Capitolo/Saggio]
Chiarini, Luigi; Anesi, Alexandre; Negrello, Sara

Maintaining projection and support of the lower face and planning for endosseous dental implant positioning require bony reconstruction of the mandible when a major defect occurred. To completely restore the anterior mandible, it is necessary to overcome the limited height of the fibula compared to the native symphyseal and parasymphyseal region; adequate bone height is a precondition for dental implant planning. Intraoral tissue reconstruction and a myofascial lining can also be performed with myofascial fibula flap or with simple/folded skin island of fibula flap. For the largest defects, a double flap (fibula osteocutaneous flap externally, radial forearm fasciocutaneous or vertical rectus abdominis myocutaneous intraorally) may be required. We briefly describe the mandibular reconstructive principles through fibula flap related to specific defects, referring to the classification proposed by Cordeiro et al.

2019 - Linfadenectomia sovraomoioidea. [Capitolo/Saggio]
Chiarini, Luigi; Anesi, Alexandre; Negrello, Sara

Lo svuotamento linfonodale sovra-omoioideo è la dissezione laterocervicale selettiva più frequentemente eseguita in caso di carcinoma del cavo orale. Con il termine “svuotamento linfonodale selettivo” si intende l’asportazione dei pacchetti linfonodali a maggior rischio di metastasi, con la preservazione di uno o più livelli linfonodali di solito rimossi durante uno svuotamento radicale. In particolar modo lo svuotamento sovraomoioideo prevede la dissezione del I-II-III livello linfonodale (ovvero al di sopra, cranialmente, rispetto al muscolo omoioideo). La possibilità di eseguire dissezioni selettive del collo si basa sul fatto che il drenaggio linfatico delle mucose del cavo orale, in pazienti con carcinoma a cellule squamose precedentemente non trattati, segue percorsi relativamente costanti e di conseguenza le metastasi linfonodali presentano un pattern di diffusione relativamente prevedibile in base alla localizzazione del tumore primitivo. Gli studi anatomici di Rouvière, Fish e Sigel (e successivamente Shah) hanno concluso che i tumori della cavità orale metastatizzano più frequentemente ai linfonodi del collo del I, II, e III livello, mentre i tumori dell’orofaringe, ipofaringe, laringe metastatizzano più frequentemente al II, III, e IV livello. Il trattamento chirurgico delle metastasi linfonodali è stato proposto ed eseguito in origine da Von Albrecht nel 1875, ai primordi della chirurgia laringea, con la sola asportazione dei linfonodi metastatici; Gluck e Sorensen asportavano anche il muscolo sternocleidomastoideo, la giugulare interna e, talvolta, la carotide. Crile nel 1898 introdusse lo svuotamento linfonodale sistematico in monoblocco con la laringectomia, dimostrando che nella sua casistica i malati così trattati sopravvivevano mediamente quattro volte di più di quelli trattati con semplice laringectomia. In seguito, circa 70 anni dopo, Suarez e Bocca iniziarono a conservare il nervo spinale accessorio, la vena giugulare interna e il muscolo sternocleidomastoideo in caso di tumori della laringe e ipofaringee con collo clinicamente negativo per localizzazioni metastatiche linfonodali. L’origine dello svuotamento selettivo, invece, non è del tutto chiara. Molti chirurghi hanno usato questo tipo di procedura per decadi senza descriverla formalmente. Per esempio, Kocher eseguiva un’asportazione parziale dei linfonodi nei pazienti con carcinoma del cavo orale e collo N0 già alla fine del diciannovesimo secolo. Con il tempo si diffuse una procedura detta “svuotamento sovraioideo” (cioè del I livello) nei casi di linfoadenopatie occulte associate ai carcinomi soprattutto del labbro. In seguito, nel 1972, Lindberg ha dimostrato che i livelli più frequentemente coinvolti in pazienti con carcinoma del cavo orale sono in genere il II e il III; nei carcinomi del pavimento della bocca e della lingua mobile il livello più frequentemente coinvolto è, invece, il I. Più tardi Byers propose i termini “anteriore” e “sovraomoioideo” per indicare le dissezioni parziali, ma solo nel 1991 si iniziò ad usare il termine selettivo per descrivere le resezioni linfonodali limitate (Academy’s Committee for Head and Neck Surgery and Oncology). In generale lo svuotamento linfonodale laterocervicale del collo può essere eseguito secondo due diversi tempi rispetto al momento dell’asportazione del tumore primario: 1) in contemporanea all’asportazione del tumore primario ed in assenza di evidenza clinica e radiologica di metastasi linfonodali laterocervicali, ovvero in stadio cN0, al fine di eradicare eventuali metastasi occulte: viene definito svuotamento elettivo o elective neck dissection. 2) successivamente all‘intervento sul tumore primario, al manifestarsi clinico o radiologico delle metastasi linfonodali laterocervicali: viene definito svuotamento terapeutico o therapeutic neck dissection. Lo svuotamento linfonodale elettivo (cN0) è abitu

2019 - Obturator nerve split for gracilis free-flap double reinnervation in facial paralysis [Articolo su rivista]
Baccarani, A.; Starnoni, M.; Zaccaria, G.; Anesi, A.; Benanti, E.; Spaggiari, A.; De Santis, G.

The use of a double-powered free muscle transfer for facial reanimation has been reported by several authors with different types of nerve coaptation. A new nerve coaptation strategy is presented herein. We performed a 1-stage double-powered free gracilis muscle flap transfer in a patient with long-standing facial paralysis by splitting the obturator nerve and anastomosing the 2 free ends to the contralateral facial nerve (through a sural graft) and to the masseteric nerve. Voluntary movement of the transferred muscle with teeth clenching was observed at 6 months after the operation and a symmetric smile with bilateral elevation of the mouth angle at 10 months. Our limited experience suggests that in case of a large cross-section of the obturator nerve, the latter can be split and sutured to the ipsilateral masseteric nerve and to the contralateral facial nerve with a sural graft by double end-to-end anastomosis.

2019 - SBF assays, direct and indirect cell culture tests to evaluate the biological performance of bioglasses and bioglass-based composites: Three paradigmatic cases [Articolo su rivista]
Bellucci, Devis; Salvatori, Roberta; Anesi, Alexandre; Chiarini, Luigi; Cannillo, Valeria

A novel bioglass composition (BGMS10), containing strontium and magnesium and characterized by an ultra-high crystallization temperature, is here employed for the first time to produce different composites with the addition of specific amounts of hydroxyapatite. After an investigation of the samples’ bioactivity in vitro in a simulated body fluid solution (SBF) – according to a widely used protocol – the biocompatibility of the new materials was tested with respect to murine fibroblasts both by direct and indirect tests, in order to evaluate possible cytotoxic effects of the materials’ eluates. Although none of the samples were cytotoxic and their bioactivity in SBF increased with the increasing amount of the glass in the composite, thus showing the best performance in the case of pure BGMS10 glass, the findings of the biological investigation did not confirm those arising from the SBF assay. Surprisingly, while the composites with the lowest glass amount showed an enhanced biocompatibility in direct tests, on the contrary their biological responsiveness is typically lower in the indirect ones, based on filtered materials’ extracts. This fact could be ascribed to the high release of particulate from the composites, which are more porous than the glassy samples: in fact, such pronounced dissolution may affect both the cell viability and the absorbance readings used in the colorimetric assays. The pure BGMS10 glass showed the best biological response only in the cell proliferation test (which is an indirect contact test), being able to stimulate cell proliferation in particular after 24 h. For these reasons, when considering bioactive glasses and bioglass-based composites, the results of direct cell culture assays should be integrated with those obtained by indirect ones, while the findings regarding the in vitro bioactivity in SBF should be interpreted with great care.

2019 - Second Vascularized Fibula Flap and Osteotomy to Correct Malocclusion [Capitolo/Saggio]
Nocini, Pier Francesco; Anesi, Alexandre; Chiarini, Luigi

For alveolar bone augmentation, a further reconstructive procedure is possible with a new revascularized fibula flap fixed onto the surface of the first fibula, placed as reconstruction of the basal bone of the mandible. Two consecutive vascularized free flaps are reported in a small series of patients affected by recurrent squamous cell carcinoma. A second fibula vascularized flap is reliable for simultaneous augmentation in symphysis, parasymphysis, and the premolar area over a previous fibula flap: implant-borne dental rehabilitation becomes practicable to improve quality of speech and diet. Malocclusion and asymmetric facial contour may follow reconstruction of the jaws with vascularized fibula flap for an inaccurate insetting procedure. The misaligned reconstructed jaw may influence the implant placement, resulting in occlusal overload that may impair the long-term survival of implant-supported prostheses. Correction of malocclusion after fibula graft may be obtained by secondary osteotomies. We described the use of a Le Fort osteotomy to correct malocclusion after fibula flap reconstruction of the maxilla. The ideal dental relationships of the osteotomized and moved jaw can be established by using a surgical acrylic splint, which is secured to the opposing dentition. The peroneal vessels can be ligated on this occasion, enabling the osteotomized jaw to move with more ease and thus proceed according to the planning.

2019 - Technique [Capitolo/Saggio]
Chiarini, Luigi; Anesi, Alexandre; Negrello, Sara

The aim of maxillary or mandibular reconstruction must be to restore not only aesthetics but also complete oral function. Cortical bone thickness, height, and bicortical structure of the fibula shaft is ideal for long-term implant-borne prosthetic rehabilitation. Fibular cortical thickness is superior with respect to the iliac crest or the scapula crest. The efficacy of dental implants placed into free fibula flaps for orofacial reconstruction has been thoroughly proved. Some authors have reported the possibility of inserting implants into the free fibula flap during the primary reconstruction. The major disadvantage of immediate implant insertion concerns the high possibility of misalignment of the fixtures. The use of oral implants in irradiated tissue is not considered to be contraindicated. The timing of the implantation procedure, with regard to the effects of irradiation on the jawbone, remains inconclusive for lack of scientific evidence. Typically, dental implants are placed 6–12 months after radiation therapy. The fibula flap is commonly harvested as osteocutaneous flap, so that a skin paddle is harvested with the fibula bone graft. The skin paddle is bulky, much thicker than the gingiva, not fixed to the bone by the periosteum, and not keratinized. Several techniques are used in soft-tissue management after a fibula vascularized graft, such as skin graft, mucosa graft, or biological membranes.

2018 - Bioglass and bioceramic composites processed by Spark Plasma Sintering (SPS): biological evaluation Versus SBF test [Articolo su rivista]
Bellucci, D.; Salvatori, R.; Cannio, M.; Luginina, M.; Orrù, R.; Montinaro, S.; Anesi, A.; Chiarini, L.; Cao, G.; Cannillo, V.

The biocompatibility of hydroxyapatite (HA), a lab-made bioglass (BGCaMIX) with high crystallization temperature and different HA/BGCaMIX composites, pro- duced by Spark Plasma Sintering (SPS), was tested with respect to murine osteocytes both by direct and indirect tests, in order to also investigate possible cytotoxic effects of the samples’ extracts. Previous investigations demon- strated that the samples’ bioactivity, evaluated in a simu- lated body fluid solution (SBF), increased with the increas- ing amount of BGCaMIX in the sample itself. Although none of the samples were cytotoxic, the findings of the bi- ological evaluation did not confirm those arising from the SBF assay. In particular, the results of direct tests did not show an enhanced “biological performance” of materials with higher glass content. This finding may be due to the high release of ions and particulate from the glass phase. On the contrary, the performance of the BGCaMIX alone is better for the indirect tests, based on filtered samples’ extracts. This work further demonstrates that, when con- sidering bioglasses and HA/bioglass composites, the re- sults of the SBF assays should be interpreted with great care, making sure that the results arising from direct con- tact tests are integrated with those arising from the indirect ones.

2018 - Bone regeneration by novel bioactive glasses containing strontium and/or magnesium: A preliminary in-vivo study [Articolo su rivista]
Bellucci, Devis; Cannillo, Valeria; Anesi, Alexandre; Salvatori, Roberta; Chiarini, Luigi; Manfredini, Tiziano; Zaffe, Davide

In this work, a set of novel bioactive glasses have been tested in vivo in an animal model. The new compositions, characterized by an exceptional thermal stability and high in vitro bioactivity, contain strontium and/or magnesium, whose biological benefits are well documented in the literature. To simulate a long-term implant and to study the effect of the complete dissolution of glasses, samples were implanted in the mid-shaft of rabbits' femur and analyzed 60 days after the surgery; such samples were in undersized powder form. The statistical significance with respect to the type of bioactive glass was analyzed by Kruskal-Wallis test. The results show high levels of bone remodeling, several new bone formations containing granules of calcium phosphate (sometimes with amounts of strontium and/or magnesium), and the absence of adverse effects on bone processes due to the almost complete glass dissolution. In vivo results confirming the cell culture outcomes of a previous study highlighted that these novel bioglasses had osteostimulative effect without adverse skeletal reaction, thus indicating possible beneficial effects on bone formation processes. The presence of strontium in the glasses seems to be particularly interesting.

2018 - Structural and ultrastructural analyses of bone regeneration in rabbit cranial osteotomy: Piezosurgery versus traditional osteotomes. [Articolo su rivista]
Anesi, Alexandre; Ferretti, Marzia; Cavani, Francesco; Salvatori, Roberta; Bianchi, Michele; Alessandro, Russo; Chiarini, Luigi; Palumbo, Carla; Bianchi, Michele

Clinical advantages of piezosurgery have been already proved. However, few investigations have focused on the dynamics of bone healing. The aim of this study was to evaluate, in adult rabbits, bone regeneration after cranial linear osteotomies with two piezoelectrical devices (Piezosurgery® Medical - PM and Piezosurgery® Plus - PP), comparing them with conventional rotary osteotomes (RO). PP was characterized by an output power three times higher than PM. Fifteen days after surgery, histomorphometric analyses showed that the osteotomy gap produced with PM and PP was about half the size of that produced by RO, and in a more advanced stage of recovery. Values of regenerated bone area with respect to the total osteotomy area were about double in PM and PP samples compared with RO ones, while the number of TRAP-positive (tartrate-resistant acid phosphatase positive) osteoclasts per linear surface showed a significant increase, suggesting greater bone remodelling. Under scanning electron microscopy, regenerated bone displayed higher cell density and less mineralized matrix compared with pre-existent bone for all devices used. Nanoindentation tests showed no changes in elastic modulus. In conclusion, PM/PP osteotomies can be considered equivalent to each other, and result in more rapid healing compared with those using RO.

2018 - The diagnostic delay of oral carcinoma [Articolo su rivista]
Marella Gian, Luca; Raschellà, Francesco; Solinas, Matteo; Mutolo, Pietro; Potenza, Saverio; Milano, Filippo; Mauriello, Silvestro; Caggiano, Bartolo; Rondinelli, Pierfrancesco°; Anesi, Alexandre°°; Migaldi, Mario°

This paper describes the results of a retrospective study that analyzed the extent and role of diagnostic delays on the development and prognosis of oral cancer. We consulted the digital archives of the Anatomy and Pathology Department of the University Hospital of Modena and Reggio Emilia for the period from 2000 to 2016, to identify all patients with oral cavity lesions according to the SNOMED coding system. In total, 645 reports of squamous cell carcinoma of the oral cavity were retrieved. Data collected from the reports was supplemented with clinical information, with particular reference to the time of onset of the first signs and/or symptoms and the time elapsed between biopsy and definitive histological diagnosis following surgery. The average delay of patients from onset of signs and/or symptoms and seeking medical care was 112 days, or about 4 months. A longer delay was found for male with respect to female patients (151 days versus 82 days respectively; p < 0.015). An average delay of 40 days was observed between the first biopsy and the postoperative histological diagnosis. Results indicate that diagnostic delays occur frequently in oral tumours and can due to both the patient's wait-and-see conduct upon appearance of the first signs and/or symptoms, and to the organizational and communicative deficiencies among the different medical specialties. In light of these results, we make the recommendation to organize information campaigns through the Public Health Departments and specific screening programs, and to introduce an operational protocol for the prevention and early diagnosis of oral cancer, involving general medicine practitioners and dentists as the main promoters.

2017 - A comparative in vivo evaluation of bioactive glasses and bioactive glass-based composites for bone tissue repair [Articolo su rivista]
Bellucci, Devis; Anesi, Alexandre; Salvatori, Roberta; Chiarini, Luigi; Cannillo, Valeria

In this work a set of novel materials for bone tissue regeneration have been tested in vivo in an animal model. In fact, despite many studies have been devoted to amorphous 45S5 Bioglass®, there is lack in the literature of works aimed to study the in vivo performance of heat-treated – and thus partially crystallized – 45S5. As widely reported, crystallization limits the bioactivity of 45S5 and is the main reason that prevents a broader use of this material. Thus, in the present work, a recently developed bioactive glass (BG_Ca/Mix) is tested, since previous investigations demonstrated that BG_Ca/Mix is particularly promising by virtue of both its high bioactivity and lower tendency to crystallize with respect to 45S5. BG_Ca/Mix sintered powders and two composites, which contain BG_Ca/Mix and an increasing percentage (20&nbsp;wt% or 70&nbsp;wt%) of hydroxyapatite (HA), were considered. As a term of comparison, 45S5 sintered powders were also studied. The samples were implanted in rabbits' femurs and harvested after 8&nbsp;weeks. The histological analysis demonstrated that BG_Ca/Mix has an osteoconductive ability slightly higher than that of 45S5 glass-ceramics, followed by that of the composites, which may represent the starting point for obtaining systems with degradation rate tailored for a given clinical application. Moreover, the 45S5 samples were locally cracked, probably because of a non-uniform dissolution in the physiological environment. On the contrary such cracks, which could lead to implant instability and unsuitable mechanical performance, were not observed in BG_Ca/Mix.

2017 - Il trattamento del collo cN0 nel carcinoma della lingua [Capitolo/Saggio]
Chiarini, Luigi; Anesi, Alexandre

Risulta universalmente riconosciuta l’importanza oncologica dello svuotamento laterocervicale terapeutico (therapeutic neck dissection - TND) in caso di evidenza clinica o radiologica di metastasi linfonodali. Lo svuotamento elettivo (elective neck dissection - END), nel caso la stadiazione clinica di malattia risulti essere T1-T2/cN0, rimane invece uno degli argomenti più dibattuti degli ultimi cinquant’anni per ragioni legate alla morbilità chirurgica della procedura di dissezione chirurgica latero-cervicale (Kokemueller et al., 2002; Carlson et al., 2006). Attualmente si possono fondamentalmente individuare due scuole di pensiero: una che sostiene la necessità di eseguire lo svuotamento laterocervicale elettivo in unico tempo con la resezione del tumore primario e l’altra che propone la strategia del watchful waiting (attento monitoraggio). Da una parte il 60-80 % dei cN0 trattati risulta privo di metastasi occulte, e pertanto appare essere iper-trattato, ovvero gravato da una maggiore morbilità data da un secondo sito chirurgico al collo (cicatrici cutanee, asimmetria laterocervicale, possibile paresi del labbro inferiore e, in particolare, dolore e perdita di funzionalità della spalla con anche pesanti ripercussioni sulla qualità di vita dei pazienti) . D’altra parte gli esami diagnostici attualmente disponibili non consentono di identificare con sufficiente certezza le metastasi linfonodali; circa il 20-40 % dei colli cN0 operati risultano in seguito avere delle metastasi occulte ed andrebbero inevitabilmente incontro a recidiva latero-cervicale di malattia, se venisse applicata la teoria del watchful waiting. Sempre a supporto dell’intervento elettivo di svuotamento laterocervicale, diversi lavori dimostrano una migliore sopravvivenza e una minor frequenza di recidive in caso di svuotamento elettivo rispetto a quello terapeutico. Finalmente, un ampio studio prospettico randomizzato condotto su 500 pazienti con carcinoma squamo-cellulare T1-T2 del cavo orale dal Professor Anil D'Cruz supporta l’importanza dello svuotamento elettivo. Questo lavoro è stato presentato al congresso annuale dell’ASCO (American Society of Clinical Oncology) e pubblicato nel New England Journal of Medicine nel 2015 (D’Cruz et al., 2015). Secondo lo studio, nei 3 anni osservati, lo svuotamento laterocervicale elettivo (END) aumenta l’overall survival del 12,5% ed il disease free-survival de 23.6% rispetto allo svuotamento terapeutico (TND). Lo stesso lavora dimostra che l’unico fattore realmente legato ad una maggior probabilità di riscontro di metastasi linfonodali sembra essere una profondità del T maggiore di 3 mm, parametro verificabile solo con l’esame istologico del pezzo operatorio e quindi argomento non applicabile per far cadere l’indicazione ad uno svuotamento elettivo. In conclusione dobbiamo considerare che circa un terzo dei pazienti con carcinoma squamocellulare orale presenta tuttora (nonostante le nuove metodiche di imaging) metastasi linfonodali occulte alla diagnosi, e che, se non trattati chirurgicamente al collo durante l’asportazione del T, hanno possibilità di dover essere rioperati a livello latero-cervicale in un secondo tempo, con una minor prospettiva di controllo locoregionale della malattia ed una peggiore prognosi, considerati il maggior volume linfonodale e la possibile invasione extranodale. Quindi, nonostante il rischio di complicanze legate allo svuotamento laterocervicale (nello studio menzionato riguardano comunque solo il 5 % dei pazienti), al momento rimane indicato intervenire in maniera elettiva nei colli cN0. Riteniamo giustificato osservare questa pratica terapeutica perlomeno fino allo sviluppo di metodiche di imaging in grado di garantire una precoce diagnosi di metastasi occulte laterocervicali. Più precisamente lo svuotamento selettivo del collo è indicato nei pazienti con carcinoma squamoso del cavo orale senza evidenza clinica o radiologica di coinvo

2017 - La Tecnologia CAD / CAM applicata alla Chirurgia Ricostruttiva della Mandibola [Relazione in Atti di Convegno]
Anesi, Alexandre; Ragoni, Matteo; Chiarini, Luigi; DE SANTIS, Giorgio

L’intento è quello di condividere le prime impressioni relative alla messa in pratica della cosiddetta «Computer Aided Surgery», (CAS) ossia della chirurgia assistita da computer, nelle ricostruzioni mandibolari con lembo libero di perone. Molti chirurghi considerano la modellazione del perone, il suo adattamento e la sintesi ai monconi mandibolari, come la fase chirurgica più impegnativa della ricostruzione, dalla cui accuratezza dipendono gli esiti chirurgici ed a cui si associa un dispendio di tempo non indifferente, capace di incidere sulla durata totale dell’intervento e, di conseguenza, sui costi associati a questo tipo di chirurgia. La svolta nella pianificazione di trattamento si è avuta con lo sviluppo della tecnologia CAD/CAM e conseguenti applicazioni in campo medico & chirurgico. CAD stà a significare «disegno assistito da computer», CAM «produzione assistita da computer». I software CAD, nati negli anni 60’, permettono di progettare, sul monitor bidimensionale di un computer, modelli tridimensionali di oggetti reali o meno. I software CAM invece sono in grado di tradurre le informazioni provenienti da un progetto CAD in istruzioni per macchinari capaci di materializzare il progetto virtuale stesso, le così dette stampanti 3D. Dime chirurgiche di taglio del perone e per l'osteotomia oncologica sono pianificate digitalmente

2017 - Role of magnesium oxide and strontium oxide as modifiers in silicate-based bioactive glasses: Effects on thermal behaviour, mechanical properties and in-vitro bioactivity [Articolo su rivista]
Bellucci, Devis; Sola, Antonella; Salvatori, Roberta; Anesi, Alexandre; Chiarini, Luigi; Cannillo, Valeria

The composition of a CaO-rich silicate bioglass (BG_Ca-Mix, in mol%: 2.3 Na2O; 2.3 K2O; 45.6 CaO; 2.6 P2O5; 47.2 SiO2) was modified by replacing a fixed 10&nbsp;mol% of CaO with MgO or SrO or fifty-fifty MgO-SrO. The thermal behaviour of the modified glasses was accurately evaluated via differential thermal analysis (DTA), heating microscopy and direct sintering tests. The presence of MgO and/or SrO didn't interfere with the thermal stability of the parent glass, since all the new glasses remained completely amorphous after sintering (treatment performed at 753&nbsp;°C for the glass with MgO; at 750&nbsp;°C with SrO; at 759&nbsp;°C with MgO and SrO). The sintered samples achieved good mechanical properties, with a Young's modulus ranging between 57.9&nbsp;±&nbsp;6.7 for the MgO-SrO modified composition and 112.6&nbsp;±&nbsp;8.0&nbsp;GPa for the MgO-modified one. If immersed in a simulated body fluid (SBF), the modified glasses after sintering retained the strong apatite forming ability of the parent glass, in spite of the presence of MgO and/or SrO. Moreover, the sintered glasses, tested with MLO-Y4 osteocytes by means of a multi-parametrical approach, showed a good bioactivity in vitro, since neither the glasses nor their extracts caused any negative effect on cell viability or any inhibition on cell growth. The best results were achieved by the MgO-modified glasses, both BGMIX_Mg and BGMIX_MgSr, which were able to exert a strong stimulating effect on the cell growth, thus confirming the beneficial effect of MgO on the glass bioactivity.

2016 - Basic and advanced endoscopic sinus surgery course: open and endoscopic cadaver dissection techniques and live surgery. [Esposizione]
Presutti, Livio; Chiarini, Luigi; Anesi, Alexandre

This course originates from the close collaboration experienced and established over many years between the three professionals most involved in the surgical treatment of lesions of the anterior skull base. We believe, and the results have proved us right, that the achievement of the best treatment in such complex anatomical regions can be born only from an accurate preoperative study, the realization of several surgical procedures and the care of every detail during the post-operative period carried out in a close collaboration among Otolaryngologists, Maxilo-Facial surgeons and Neurosurgeons. The relatively recent introduction of endoscopic surgery and the huge expansion of the latter has further expanded the possibilities of collaboration. On the other hand those who want to approach to this type of pathologies necessarily have to know not only the techniques and possibilities of endoscopy but also the open techniques which are essential to face certain situations or clinical manifestations. The experience of many years of shared work between two surgical university schools with great traditions such as Modena and Verona besides a personal friendship established over time has enabled us both to joint the three specialties and to create a group that is inspired by the same principles.

Ferretti, Marzia; Cavani, Francesco; Checchi, Marta; Smargiassi, Alberto; Anesi, Alexandre; Salvatori, Roberta; Chiarini, Luigi; Palumbo, Carla


2016 - Orbital approaches for primary and secondary tumours [Poster]
Negrello, S; Anesi, Alexandre; Casadei, M; Chiarini, Luigi

Background: Orbital tumours are uncommon and represent approximately only 3.5 - 4 % of ophthalmic disease. Most published articles report case report, comparative studies with small numbers of patients or non-comparative studies with limited statistical power to provide clear treatment and reconstructive recommendations. Purpose: This paper reports our experience in treating orbital tumours. In particular, we analyzed both epidemiology, histology, methods of treatment and follow up. Particular emphasis is laid on the complications and aesthetic results of the different surgical approaches. Method: A retrospective study was carried out of 152 patients with orbital masses treated at Head and Neck Surgery Department of the University Hospital of Modena between January 2001 and the end of March 2016. The follow-up period begins in 2001 and finish by the 31th of March 2015. The survival has been calculated according to Kaplan-Meyer method (using IBM SPSS Statistics 20). Discussion: The median survival was ninety-six months. The cumulative survival at 12 months was 88 %; it came to 78 % in 24 months. The cumulative survival at 5 aa (60 months ) was 77 %. The lowest survival was showed in patients treated with an extensive osteotomy or exenteration. This result, however, could not be linked to the surgical approach but it could be due to the poor prognosis of the more advanced tumours and to the intracranial lesions involvement. Patients undergoing extensive osteotomies presented the greatest number of complications : 25 % complained of diplopia , 10% a decrease of visual acuity and 15 % had lagophthalmos , in two cases with epiphora . Conclusion: Preserving the contents of the orbital cavity and function is often possible after radical excision. However, conservative purposes have not to impair the oncologic efficacy.

Anesi, Alexandre; Casadei, M; Negrello, S; Chiarini, Luigi

BACKGROUND: Segmentation of vascularized bone flaps with piezoelectrical device is a valuable alternative to conventional cutting methods because it improves the intraoperative safety of the procedure. The time needed for completion of a single osteotomy with the piezoelectric device is longer than with the oscillating saw. However, the time normally needed to dissect and protect both the periosteum and the pedicle at each osteotomic site is greatly reduced. In 2015 a new piezoelectrical device suitable for highly mineralised bone and significantly efficient through all the cutting depth was engendered. Hardness and thickness of human fibula bone cortex may be fitting for this new piezoelectrical osteotome. AIM: We present and discuss the use a new generation of the piezoelectric bone-cutting device in microvascular free bone flap for the reconstruction of jawbone defects. The aim of this study was to evaluate on human fibula the time required for completion of each osteotomy comparing new piezoelectrical device and previous commercial device. A comprehensive study that evaluates and compares histomorphometry and histology of bone surfaces created with two piezosurgical devices is carried out. MATERIALS AND METHOD: In 2016 seven consecutive patients underwent microsurgical reconstruction of the jaws. One specimen from each fibular bone diaphysis was harvested with the piezoelectric device and histologically evaluated. CONCLUSIONS: The new generation piezoelettrical device halves the time needed for linear and wedge osteotomies on human fibula flap compared to tradizional piezoelectrical device. No significant histological and histomorphometrical differences are detected between bone surfaces osteotomized with both devices.

2015 - Bioactive glass/hydroxyapatite composites: Mechanical properties and biological evaluation [Articolo su rivista]
Bellucci, Devis; Sola, Antonella; Anesi, Alexandre; Salvatori, Roberta; Chiarini, Luigi; Cannillo, Valeria

Bioactive glass/hydroxyapatite composites for bone tissue repair and regeneration have been produced and discussed. The use of a recently developed glass, namely BG_Ca/Mix, with its low tendency to crystallize, allowed one to sinter the samples at a relatively low temperature thus avoiding several adverse effects usually reported in the literature, such as extensive crystallization of the glassy phase, hydroxyapatite (HA) decomposition and reaction between HA and glass. The mechanical properties of the composites with 80wt.% BG_Ca/Mix and 20wt.% HA are sensibly higher than those of Bioglass® 45S5 reference samples due to the presence of HA (mechanically stronger than the 45S5 glass) and to the thermal behaviour of the BG_Ca/Mix, which is able to favour the sintering process of the composites. Biocompatibility tests, performed with murine fibroblasts BALB/3T3 and osteocites MLO-Y4 throughout a multi-parametrical approach, allow one to look with optimism to the produced composites, since both the samples themselves and their extracts do not induce negative effects in cell viability and do not cause inhibition in cell growth.

2014 - Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ) [Capitolo/Saggio]
Pozzi, Samantha; Anesi, Alexandre; Generali, Luigi; Bari, Alessia; Consolo, Ugo; Chiarini, Luigi

Osteonecrosis of the jaw (ONJ) is a rare condition that has been mainly related to the treatment with i.v. bisphosphonates in patients affected by cancer bone disease. The ethiopathology is still unknown and the frequency is between 0.8 and 12 %. It can appear in edentulous patients, but invasive procedures have been demonstrated to increase the risk of developing this complication. Few cases have been described in the endodontic literature. In the next chapter, we will describe ONJ, will analyze the data from literature, and will report expert opinions and guidelines about the best clinical practice in the endodontic fi eld. Finally, since data in this field are limited, we would like to underline that the best treatment plan for cancer patients receiving bisphosphonates and requiring dental procedures is a multidisciplinary, case-by-case approach.

Chiarini, Luigi; Anesi, Alexandre; Pertici, G; Perale, G.

The treatment of anterior and lateral skull base tumors has always constituted a complex surgical challenge: extensive bony demolitions produce aesthetic deformities that need accurate reconstructions. Indeed, highly destructive procedures increased the need to introduce new reconstructive techniques. Wide defects, e.g. those involving more than a single orbital wall, have to be reconstructed with solid tissues such as autologus grafts or alloplastic materials. Surgical visual limits may reduce the possibility to properly repair the three-dimensional bony architecture of the craniofacial skeleton: because of the nonlinear nature of the bone in the craniofacial skeleton, even small degrees of error can lead to poor outcomes. Here we investigated the innovative application of custom-made bone grafts in a case of skull base reconstructive surgery, a technique that is not previously reported. Innovations applied to this case were multiple: basing on high resolution patient’s CT scans, virtual surgery and computer-aided design were used to plan resection; contralateral disease-free skull base was used as a reference and mirroring technique was used to create the ideal grafts, which were then manufactured accordingly using the new composite custom-made bone grafts (SmartBone® on Demand™). SmartBone® is shaping resistant and offers high tenacity to screws and surgical fixation manoeuvres, because it is produced by combining bovine mineral bone structures with biopolymers and cell nutrients (polysaccharides). The patient underwent resection of a meningioma in the spheno-orbital-temporal region. The neurosurgeon resected the meningeal involved district, which was then reconstructed with a collagenous membrane. SmartBone® on Demand™ were then very precisely grafted into destination site. During follow-up, nor cerebrospinal fluid leakage nor intracranial infection were registered. Postoperative CT scans showed excellent stability and integration of all bone grafts; postoperative morphological results are satisfactory. Outcomes confirm the high reliability and accuracy of virtual surgical planning and grafts design, which, together with SmartBone® high performances, allow producing very precise and stable custom-made grafts and, finally, addressing the previously unmet needs in skull base reconstructive surgery.

Chiarini, Luigi; Albanese, M; Anesi, Alexandre; Nocini, Pf

Introduction: Many devices have been proposed for preserving the preoperative position of the mandibular condyle during bilateral sagittal split osteotomy. Accurate mandibular condyle repositioning is considered important to obtain a stable skeletal and occlusal result, and to prevent an impairment of previous temporomandibular disorders (TMD). Objective: This study is a preliminary report concerning the use of a new condylar positioning device (Medicon, Tuttlingen, Germany) in a group of 5 dysfunctional TMJ patients with the aim of maintaining the preoperative position of the condyle during orthognathic surgery. Methods: Five TMJ dysfunctional patient underwent a bimaxillary surgery for dento-scheletal malocclusion. Fabrication of preoperative positioning wax bite was done according to an optimized proximal segment position as assessed in clinical examination, through stabilization splints and TMJ cone beam tomography study. The positioning wax bite was set in occlusion, fixed by intermaxillary wires, and positioning plates were adapted on the anterior mandibular ramus thorough an intraoral approach in female patients, while a transcutaneous via(trocar device) is chosen in male patients. The plates are connected with removable extraoral articulated arms to a modified cranio-facial bow, fixed on temporal/parietal bones by means of transcutaneous pins. The articulated joints of the arms are locked, allowing the registration of optimized proximal segment position in accordance of the preoperative wax bite. Bimaxillary surgery was then performed according to the planning. Before mandibular fixation with 2 rigid titanium plate on each side, the articulated locked arms are repositioned and connected to positioning plates. Mandibular fixation is then completed. The articulated arms and the positioning plates are removed. The dental and skeletal stability, signs and symptoms of TMD, the comparison of preoperative and post-operative TMJ cone beam tomography are evaluated during the follow-up period. Questions: 1 - Anterior distraction of the condyle from the fossa during orthognatic surgery produces: a) Immediate skeletal relapse b) Spontaneous and uneventful occlusal stabilization c) Condylar resorption d) All of the above 2-Late skeletal relapse is likely attributable to: a) Muscle memory b) Proximal segment rotation and posterior repositioning of the condyle c) Any mandibular advancement d) None of the above 3-Condylar positioning devices in mandibular orthognathic are: a) Often used in orthognathic surgery b) Barely used while manual repositioning is preferred c) All of the above d) None of the above 4-TMJ dysfunctional patients that underwent orthognathic surgery with rigid fixation: a) Always report a worsening on TMJ sign and symptoms after surgery b) Can achieve an improving in pain and functional status after surgery c) All of the above d) None of the above

2014 - Expression of CD133 Correlates with Tumor Stage, Lymph Node Metastasis and Recurrence in Oral Squamous Cell Carcinoma [Articolo su rivista]
Reggiani Bonetti, L; Migaldi, Mario; Boninsegna, A; Fanali, C; Farina, M; Chiarini, Luigi; Anesi, Alexandre; Cittadini, A; Leocata, P; Maccio, L; Sgambato, A.

Objective: CD133 is a pentaspan membrane protein expressed by the so-called cancer stem cells (CSC) in the majority of human cancers. The aim of this study was to analyze CD133 expression levels in specimens of oral cancer and to evaluate its relation with disease evolution. Methods: Expression of the CD133 protein was evaluated by immunostaining in a series of oral squamous cell carcinoma (OSCC) and its relation with traditional prognostic indicators and the clinical outcome of patients was analyzed. Results: CD133 expression was highly variable amongst different samples with a median percentage of positive cells of 5 (range 0 - 80; mean = 11) and CD133 staining was not detectable in tumor cells in 29 (43%) cases. No correlation was observed with age at diagnosis, gender and grading while a significant correlation was observed with tumor stage. Kaplan-Meier curves of disease-free survival displayed a significant separation between the negative and positive groups of patients (p = 0.001 by log-rank test) but CD133 staining did not confirm to be an independent predictor of clinical outcome in a multivariate analyses. Conclusion: Expression of CD133 was detectable in the majority of OSCC samples and correlated significantly with tumor stage and the clinical outcome of patients in terms of disease-free survival. Further studies are warranted on a larger series of cases to elucidate the role of CD133 in the development and progression of OSCC and its suitability as a prognostic biomarker.

Anesi, Alexandre; Palumbo, Carla; Ferretti, Marzia; Salvatori, Roberta; Cavani, Francesco; Chiarini, Luigi

The number of available ultrasonic osteotomes has remarkably increased. In vitro and in vivo studies have revealed differences between conventional osteotomes, such as rotating or sawing devices, and ultrasound-supported osteotomes (Piezosurgery®) regarding the micromorphology and roughness values of osteotomized bone surfaces. Objective: the present study compares the micro-morphologies and roughness values of osteotomized bone surfaces after the application of rotating and sawing devices, Piezosurgery Medical® and Piezosurgery Medical New Generation Powerful Handpiece. Methods: Fresh, standard-sized bony samples were taken from a rabbit skull using the following osteotomes: rotating and sawing devices, Piezosurgery Medical® and a Piezosurgery Medical New Generation Powerful Handpiece. The required duration of time for each osteotomy was recorded. Micromorphologies and roughness values to characterize the bone surfaces following the different osteotomy methods were described. The prepared surfaces were examined via light microscopy, environmental surface electron microscopy (ESEM), transmission electron microscopy (TEM), confocal laser scanning microscopy (CLSM) and atomic force microscopy. The selective cutting of mineralized tissues while preserving adjacent soft tissue (dura mater and nervous tissue) was studied. Bone necrosis of the osteotomy sites and the vitality of the osteocytes near the sectional plane were investigated, as well as the proportion of apoptosis or cell degeneration. Results and Conclusions: The potential positive effects on bone healing and reossification associated with different devices were evaluated and the comparative analysis among the different devices used was performed, in order to determine the best osteotomes to be employed during cranio-facial surgery.

2014 - Sol-gel derived bioactive glasses with low tendency to crystallize: synthesis, post-sintering bioactivity and possible application for the production of porous scaffolds. [Articolo su rivista]
Bellucci, Devis; Sola, Antonella; Salvatori, Roberta; Anesi, Alexandre; Chiarini, Luigi; Cannillo, Valeria

A new sol-gel (SG) method is proposed to produce special bioactive glasses (BG_Ca family) characterized by a low tendency to devitrify. These formulations, derived from 45S5 Bioglass®, are characterized by a high content of CaO (45.6 mol%) and by a partial or complete substitution of sodium oxide with potassium oxide (total amount of alkaline oxides: 4.6 mol%), which increases the crystallization temperature up to 900°C. In this way, it is possible to produce them by SG preserving their amorphous nature, in spite of the calcination at 850°C. The sintering behavior of the obtained SG powders is thoroughly investigated and the properties of the sintered bodies are compared to those of the melt-derived (M) counterparts. Furthermore, the SG glass powders are successfully used to produce scaffolds by means of a modified replication technique based on the combined use of polyurethane sponges and polyethylene particles. Finally, in the view of a potential application for bone tissue engineering, the cytotoxicity of the produced materials is evaluated in vitro.

2014 - Surgical Treatment of Unilateral Condylar Hyperplasia With Piezosurgery [Articolo su rivista]
Chiarini, Luigi; Massimo, Albanese; Anesi, Alexandre; Pier Francesco, Galzignato; Carmen, Mortellaro; Pierfrancesco, Nocini; Dario, Bertossi

INTRODUCTION: Unilateral condylar hyperplasia (UCH) is a disorder of unknown etiology mainly seen in growing patients, which results in facial asymmetry. High condylectomy alone or in association with orthognathic surgery can improve the occlusion and the facial aesthetics. MATERIALS AND METHODS: Between 2005 and 2012, a total of 5 patients underwent high condylectomy for UCH using a piezoelectric cutting device. All patients were treated postoperatively with functional rehabilitation. RESULTS: The long-term follow-up showed that all patients had a satisfactory temporomandibular joint articular function associated with stable occlusion without any recurrence of further condylar growth. CONCLUSIONS: High condylectomy in the surgical treatment of unilateral UCH seems to be the procedure of choice in growing patients. The use of a piezoelectric cutting device allows a safe and less invasive high condylectomy.

Anesi, Alexandre; Salvatori, Roberta; Chiarini, Luigi

Biomaterials for reconstruction of bony defects of the skull comprise of osteosynthetic materials applied after osteotomies or traumatic fractures and materials to fill bony defects which result from malformation, trauma or tumour resections. Other applications concern functional augmentations for dental implants or aesthetic augmentations in the facial region. The wide range of biomaterials available on the market, together with lack of established criteria to guide the use of a specific biomaterial in a particular application, has resulted in different surgeons using different materials, with no uniformity in clinical application. The optimal biomaterial that meets every requirement (e.g. biocompatibility, stability, intraoperative fitting, product safety, low costs etc.) does not exist. The different material types are (autogenic) bone and many alloplastics such as metals, ceramics, plastics and composites. We discuss our clinical experience in the use of biomaterials for craniofacial application and we present our experience with some experimental laboratory studies . Based on literature review, we present guidelines for use of different biomaterials in maxillo-facial surgery.

2013 - Commentary to: An aggressive ameloblastic fibroma in a 9‑year‑old child treated with buccal fat graft [Recensione in Rivista]
Anesi, Alexandre

Benign odontogenic tumors comprise a complex group of lesions described in the 2005 WHO classification based on the presence of odontogenic epithelium, odontogenic ectomesenchyme, or both. Ameloblastic fibroma (AF) is defined in WHO classification as “neoplasm composed of proliferating odontogenic epithelium embedded in a cellular ectomesenchymal tissue that resembles dental papilla, and with varying degrees of inductive change and dental hard tissue formation. Both the epithelial and the connective tissue components of AF are neoplastic.[1] The neoplastic nature of AF is supported by reports of recurrence after surgery and by cases of malignant transformation from a pre‑existing AF.[2,3] AF is a rather uncommon tumor, accounting for only 2.5% of all odontogenic tumors. AF raises at any age, ranging from 6 months to 42 years (mean 3.6-15.5 years); it does not show sex predilection. The lesion occurs in nearly 50‑80% of cases in posterior areas of the mandible, molar, or premolar locations as well. About 25% of AF are associated with permanent tooth eruption disturbances and impacted tooth, affecting several teeth too.[4] The rare extraosseous and soft tissue localization of the lesion is defined “peripheral AF”. The initial and small lesions are asymptomatic, whereas large and advanced ones lead to swelling and jawbone deformities.[2,5] The dimension and growth of the lesion are not related with patient’s complain, and the neoformation is frequently discovered accidentally during a simple dental radiological examination.[4] AF may appear radiographically as a well‑defined uni or multilocular radiolucent lesion, giving rise to expansion of the cortex, associated or not with the crown of an unerupted tooth.[2,3,5] Differential diagnosis may involve dentigerous cyst and ameloblastoma on a radiological point of view.[4,6] Tumor size varies from 1 to 8.5 cm.[3,5] Amina et al. described an exceptionally large AF localized in the upper jaw, unlike the most common site in the posterior mandible.[7] AF exhibits a slower clinical growth than, for example, an unicystic ameloblastoma, and it does not demonstrate an infiltrative pattern among trabeculae of the surrounding bone. It produces a enlargement of jawbone through a gradual expansion of cortex so that bony surface appears intraoperatively smooth.[4,5] Conservative or extensive (radical) approaches over AF treatment are advocated by different authors. In consideration of the innocuous behavior of the lesion, several authors proposed a meticulous enucleation or curettage as the initial treatment, keeping a block resection for recurrence.[5] Recurrence rate after surgery is a controversial issue, and it is estimated between 18.3 and 43.5%.[2,3] Residual tumor left at the time of curettage or enucleation gives rise to recurrence, and this induce some authors to advocate a more extensive surgery as first removal of the lesion. Zallen and coworkers recommends, in detail, a wide excision of the tumor unless a significant cosmetic deformity is produced.[3] Detection of residual tumor and early recurrence is possible through a long‑term postoperative control. The follow‑up management does not have a well‑defined protocol. Pereira plans to see the patient twice a year and to obtain TC/OPT on yearly basis for 2 years; any suspicion of recurrence needs earlier clinical and radiological control.[8] Long‑term follow‑up carried out by different authors report no recurrence after conservative procedure (enucleations and curettage).[2,3,5] Recurrence of AF may potentially occur as the malignant histological counterpart, i.e., as an ameloblastic fibrosarcoma. Ameloblastic fibrosarcoma develops de novo or in recurrent fibro‑odontoma or AF. The malignant transformation in an ameloblastic fibrosarcoma is rare, even though 30‑45% of ameloblastitc has developed in pre‑existing or recurrent AF or in ameloblastic fibro‑odotomas.[9] Ameloblastic fibrosarcoma

2013 - How to improve retromandibular transmasseteric anteroparotid approach for mandibular condylar fractures: our clinical experience [Articolo su rivista]
Salgarelli, Attilio Carlo; Anesi, Alexandre; Bellini, Pierantonio; G., Pollastri; D., Tanza; S., Barberini; Chiarini, Luigi

Fractures of the mandibular condyle are common and account for 25–35% of all mandibular fractures reported in the literature. Even with the development of a consensus on the preference for open reduction and internal fixation of these fractures, the clinician is still faced with a dilemma concerning the optimal approach to the ramus–condyle unit. Limited access and injury to the facial nerve are the most common problems. The most commonly used extraoral approaches are the submandibular, retromandibular and preauricular methods. In this study, we propose a modified cosmetic preauricular incision with a short end in the neck, to improve the transmasseteric anteroparotid (TMAP) approach previously described by Wilson et al. in 2005. We retrospectively analysed 13 patients treated in our department for mandibular condylar fractures. Post-operative complications, occlusal status, interincisal opening and joint tenderness were evaluated at 3 months after surgery. The wider skin incision described here provides a convenient approach for open reduction and rigid internal fixation, and good results were obtained. The follow-up ranged from 6 to 40 months.

2013 - Microsurgical reconstruction of the mandible in a patient with evans syndrome: a case report and review of the literature [Articolo su rivista]
Bedogni, Alberto; Anesi, Alexandre; Fior, Andrea; Bettini, Giordana; Nocini, Pier Francesco

In this report, we describe the first successful case of microvascular free tissue transfer in a patient with Evans Syndrome (ES), a rare form of idiopathic thrombocytopenic purpura (ITP) and associated autoimmune hemolytic anemia (AIHA). Microvascular surgery in the setting of ES is likely to have higher complication rates because of the increased risk of postoperative bleeding and free flap thrombosis. The case presented here opens up to the feasibility of microvascular reconstruction of patients with coagulation disorders like ES. Every effort should be made to control for hemolytic, thrombocytopenic, and thrombophilic states associated with ES. In the absence of evidence-based treatment guidelines for ES, personalized treatment protocols with high-dose corticosteroids, immunoglobulin, and postoperative anticoagulation regimen are highly recommended.

2013 - Retrospective analysis of orbital floor fracture: our clinical experience [Articolo su rivista]
Anesi, Alexandre; Chiarini, Luigi

Aim. This retrospective study aimed at investigating indications, surgical approaches, and the materials used for orbital floor reconstructions, as well as the clinical followup, particularly with regard to postoperative complications. Methods. This study comprised 120 patients who underwent surgery for orbital floor fractures between 2001 and 2011. Diagnosis and treatment were based on both physical examination and orbital CT scan. Patients were retrospectively analyzed for data, such as mechanism of injury, classification of fracture, and complications. Results. The most common cause of injury was physical assault followed by traffic accidents. Surgery was performed with a mean delay of 5 days after the incident. Subciliary lower eyelid incision was the most common surgical approach to the orbital floor, followed by mid lower eyelid incision and transconjunctival lower-eyelid approach. For orbital floor reconstruction, collagenous membrane derived from bovine pericardium (65%) is mainly used, followed by titanium mesh (35%); 18.0% of patients showed postoperative complications: 10.0% presented transient hypesthesia, 4.2% transient diplopia, 2.0% enophthalmos, 1% visible scar and 0.8% from scleral show. Conclusion. The main goal of this report is to discuss indications and timing for surgical repair of orbital floor fracture fractures and other facial fracture. Complications due to surgery are described.

2012 - Absence of adjuvant radiotherapy may be an additional criteria in diagnosing a branchiogenic squamous cell carcinoma: a case report [Articolo su rivista]
Anesi, Alexandre; Pollastri, G; Bondì, V; Barberini, S; Chiarini, Luigi

Branchiogenic carcinoma is extremely rare. The ma-jority of branchiogenic carcinomas are cystic metas-tases originating in the tonsils, and not true carcino-mas arising in a branchial cleft cyst. Isolated cystic neck lesions necessitate a thorough search for a primary tumor, as with other occult primaries pre-senting with cervical metastases. As the existence of primary branchiogenic carcinoma is controversial, Martin and colleagues and then Khafif and coworkers established a series of widely accepted criteria to recognize this type of carcinoma.We report a case of a large cervical mass, consistent with a branchiogenic carcinoma of the second bran-chial arch. The patient underwent excision of the neck mass through a radical neck dissection. The cyst wall was found to have squamous cell carcinoma arising from the benign epithelium. Follow-up at 7 years revealed no evidence of recurrence. All diagnostic criteria for a true branchiogenic carcinoma were met in this case. The absence of adjuvant irradiation is a further confirmation that the mass is not a cystic node metastasis but a carcinoma arised from within a branchial cleft cyst.)

2012 - Patologie della base-cranica anteriore con Piezosurgery [Abstract in Atti di Convegno]
Anesi, Alexandre

.PIEZOSURGERY® Stato dell’arte e prospettive Chirurgia Cranio Facciale Neurochirurgia

Anesi, Alexandre; Pollastri, G; Barberini, S; Chiarini, Luigi

Advanced sinonasal tumours often present with orbital involvement. Surgical treatment and radical excision are also possible, preserving the eye. Oncological safety and functional outcome of the preserved eye are the counterpart in orbital preservation surgery. Irrespective of the orbital invasion, tumour histology influences the prognosis. Surgical approaches to the orbit in sinonasal tumour are divided in anterior and posterolateral procedures. The combined transfacial and trancranial surgical approaches have been well described in the literature for craniofacial resection, when the anterior or medium skull base are involved. Multidisciplinary collaboration with microscopic and/or endoscopic control have improved surgical technique to extirpate tumours extended to dura, spehenopalatine area and pterygomaxilmary fissure, infratemporal fossa, roof of nasopharynx and apex of orbit. We describe the multiphase combined surgical approach with maxillofacial, otolaryngology and neurosurgical collaboration in sinonasal tumour treatment.

Anesi, Alexandre; Barberini, S; Pollastri, G; Ferrari, C; Chiarini, Luigi

The use of temporalis myofascial flap (TMF) as a pedicled flap in craniofacial reconstructive surgery is well established. This technique may provide a cosmetic deformity of the temporal fossa with an asymmetric contour of the head. Reconstruction of this donor site deformity is desirable. We report the use of polymethyl-methacrylate (PMMA) (Palacos ®). From January 2009 to December 2011, 11 patients (6 men and 5 women) aged 81 to 56 years (mean 67) were treated. Ten patients had squamous cell carcinoma and 1 mucoepidermoid carcinoma of minor salivary glands in the upper jaw. The oncological defects were reconstructed with TMF and the temporal fossa was simultaneously filled with PMMA. A retrospective review of the postoperative complications (hematoma, seroma) and the aesthetical results was conducted. All patients were contacted 6 months later by phone and provided with information pertaining to the aims of this study. The patients were then instructed on how to fill out the relevant questionnaires. Aesthetic results were judged satisfactory from all patients. The hemicoronal skin flap healed uneventfully in all patients and did not cause a visible scar even to bald male patients. In our group of patients no surgical seroma or hematoma in temporal fossa were observed. PMMA reconstruction was characterized by excellent biocompatibility with no inflammatory activation. The symmetry of temporal fossa was judged satisfactory. Intraoperative cast-molded camouflage of the temporalis flap donor site with PMMA is a feasible, accurate, fast, and cost-efficient technique that results in excellent cosmetic.

2011 - Sinonasal tumors with orbital involvement: the combined approach [Relazione in Atti di Convegno]
Anesi, Alexandre; Chiarini, Luigi

Advanced sinonasal tumors often present with orbital involvement. Surgical treatment and radical excision are also possible preserving the eye. Oncological safety and functional outcome of preserved eye are the counterpart in orbital preservation surgery. Irrespectively of the orbital invasion, tumor histology influences the prognosis. Surgical approaches to the orbit in sinonasal tumor are divided in anterior and posterolateral procedures. The combined transfacial and trancranial surgical approach have been well described in the literature for craniofacial resection, when the anterior or medium skull base are involved. Multidisciplinary collaboration with microscopic and/or endoscopic control have improved surgical technique to extirpate tumors extended to dura, spehenopalatine area and pterygomaxilmary fissure, infratemporal fossa, roof of nasopharynx and apex of orbit. We describe the multiphase combined surgical approach whit maxillofacial, otolaryngology and neurosurgical collaboration in sinonasal tumor treatment.

2011 - Synergistic Use of Local Flaps for Total Lower Lip Reconstruction [Articolo su rivista]
Salgarelli, Attilio Carlo; Bellini, Pierantonio; Magnoni, Cristina; Anesi, Alexandre; Collini, M.

The loss of tissue in the lower lip has beentreated using different techniques dependingon the size and location (median or lateral) of thedefect.1,2 Plastic surgery for small defects of up totwo-thirds of the lower lip relies on surgicaltechniques such as direct suturing of the resectionmargins with or without Z-plasty. The methodsthat Gillies and Millard,3 Estlander,4 Abbe´,5 andKarapandzic6 proposed, as well as the staircasetechnique,7 have been used for reconstructionsinvolving up to two-thirds of the lip, whereas theproximity of the flaps is suitable for treatingcomplete lower lip losses, according to Von Bruns,8Bernard,9 and Bernard-Freeman-Fries.10–12The multiplicity of techniques reported in the literatureindicates that there is no ideal method fortotal lower lip reconstruction. It is generally agreedthat reconstruction after resection of more thantwo-thirds of the lower lip produces visible scarsand alters the kinetics of smiling.1,2,7The Sabattini-Abbe´ flap is a full-thickness one-lipflap that is pedicled on the superior or inferiorlabial vessels and rotated 180° to fit into the defectof the opposite lip. The Sabattini-Abbe´ flap can beused for reconstructing up to two-thirds of the lip.The staircase technique, used to close full-thicknessdefects of up to two-thirds of the lower lip, is basedon the advancement flap. Johanson and colleaguesfirst described it in 1974,13 and by Dado andAngelats,14 Stiernberg,15 Kuttenberger and Hardt16and Salgarelli and colleagues7 subsequentlymodified it. Reconstruction of the lower lip isperformed using a lateral advancement flap fromthe lateral parts of the lip and chin, in a stepwisefashion.7Here, we propose the synergistic use of thestaircase technique and a Sabattini-Abbe´ flap forreconstructions involving more than two-thirds ofthe lower lip (Figures 1A and B).

2008 - Ameloblastic fibroma in a 6-year old child:case report. [Abstract in Rivista]
Anesi, Alexandre; Bissolotti, G.; Toller, N.; Corrocher, G.; Chiarini, Luigi; Nocini, P. F.

Ameloblastic fibroma (AF) is defined in WHO classification as a ''neoplasm composed of proliferating odontogenic epithelium embedded in a cellular ectomesenchymal tissue that resembles dental papilla, and with varying degrees of inductive change and dental hard tissue formation''. AF is a rather uncommon tumor, accounting for only 2.5% of all odontogenic tumors. AF is a true mixed tumor, in which the epithelial and ectomesenchymal elements are neoplastic. AF raises at any age, ranging from 6 months to 42 years (mean 14.6 to 15.5 years); it does not show sex predilection. The lesion occurs in nearly 70% of cases in posterior areas of the mandible. Patients exhibit swelling of the jaw; pain is not usually described. Authors present a clinical and surgical management of an early onset of a large mandibular ameloblastic fibroma in a 6-year-old girsl.

2008 - Genioplasty with piezosurgery [Abstract in Rivista]
Turra, M.; Bertossi, D.; Bissolotti, ; Anesi, Alexandre; Chiarini, Luigi; Nocini, P. F.

Aims: The chin is the most prominent and median sector of the lower third of the face giving harmony to nose and lips. We present the application of piezoelectric bone cutting device for the correction of different chin deformities. The distinctive characteristics of this device allows us to avoid or reduce the immediate genioplasty complications. Methods: 25 cases of defective chin have been treated from January 2006 to April 2007. Intraoral chinplasty was performed during the correction of dentofacial dysmorphisms or associated to nasal surgery. We used a piezoelectric cutting device to perform different osteotomies and if necessary, different kind of interpositional grafts were used to stabilize bony segments. Results: We observed a more precise and thin osteotomies (100% of cases), a reduced intraoperative bleeding (92%) with light degree of postoperative hematoma, no nervous injuries (100%, slight paresthesia 36%) and patients’ satisfaction (96%). Discussion: Chinplasty represent one of the most common ancillary procedures and may be associated with corrective surgery of skeletal bases in dentofacial dysmorphisms. Mental nerve injuries, asymmetries, intraoperative bleeding are the main immediate complications of genioplasty. Distinctive characteristics of ultrasonic piezoelectric osteotomy are selective cutting of only mineralized structure with less risk of vascular and nervous damage (microvibrations), intraoperative precision (thin cutting scalpel and no macrovibrations), blood free site (cavitation effect). In our experience, piezoelectric cutting device, compared to saw and drill, enables us to reduce or avoid immediate complications of chin surgery, helping the surgeon to reach patients’ satisfaction.

2008 - Gingival Hyperplasia and PAI-1: a case report [Abstract in Rivista]
Massimo, Albanese; Acquilini, S.; Toller, N.; Bertossi, D.; Corrocher, G.; Anesi, Alexandre; Nocini, P. F.

Objectives: Gingival hyperplasia is a volumetric augmentation, related to a local or systemic pathology, or drug assumption. Gingival hyperplasia with plasminogen deficit is a rare condition caused by fibrin depositing on connective tissue. This paper de- scribes a case of gingival hyperplasia, related at hyper expression of PAI-1, with normal plasminogen level. Clinical case: S.N., female, aged 18, was admitted presenting diffuse gingival hyperplasia with absence of major risk factors. Anamnesis revealed a total relapse after a previous complete gingivectomy performed 2 years before. Clinical and radiolog- ical evaluation confirmed the absence of periodontal disease. Hematochemical-serological-genetic set-up revealed the follow- ing: PLT 132 E+09/L, RDW 12.9%, P-PT 1.25 INR, P-APTT 1.33, vWF 43%, RISTOCETINIC CO-FACTOR 34%, desmo- pressin test: positive, homozygosis 4G for PAI-1 gene, heterozy- gosis for VLF and for XIIIF (Val34Leu) and for MTHFR (C677T and A1298C), absence of polymorphism in GpIIIa (Leu33Pro). Histological evaluation showed evidence of gingival tissue with a severe fibrin depositing and chronic inflammation. Therapy protocol included: a full mouth gingivectomy and gin- givoplasty in local anaesthesia, professional dental care every 3 months, a soft diet. After a five years follow up no evidence of relapse is observed. Conclusions: Recurrent gingival hyperplasia, related to altered blood PAI-1 level, is a rare condition, still to be properly de- fined. The action mechanism is referred to a genetic set up (homozygosis 4G for PAI-1 gene) that, arising PAI-I blood levels, inhibits plasminogen activation and so fibrin degradation. Fibrin is produced where tissue is affected by inflammation and regeneration, like in gingival mucosa while chewing

2008 - I cianoacrilati in chirurgia orale. [Articolo su rivista]
Giannone, N.; Anesi, Alexandre; Ciavarella, D.; La Torretta, G.; Di Libero, C.

Utilizzo dei ciano-acrilati nella sutura della mucosa del cavo orale a seguito din un accesso chirurgico.

2008 - Mandibular ameloblastic fibroma in 6-years-old girl: a case report. [Articolo su rivista]
Anesi, Alexandre; Albanese, M; Gerosa, R; Corrocher, G; Gambarini, G; Nocini, P. F.

Ameloblastic fibroma (AF) is defined in WHO classification as a ''neoplasm composed of proliferating odontogenic epithelium embedded in a cellular ectomesenchymal tissue that resembles dental papilla, and with varying degrees of inductive change and dental hard tissue formation''. AF is a rather uncommon tumor, accounting for only 2.5% of all odontogenic tumors. AF is a true mixed tumor, in which the epithelial and ectomesenchymal elements are neoplastic. AF raises at any age, ranging from 6 months to 42 years (mean 14.6 to 15.5 years); it does not show sex predilection. The lesion occurs in nearly 70% of cases in posterior areas of the mandible. Patients exhibit swelling of the jaw; pain is not usually described. Authors present a clinical and surgical management of an early onset of a large mandibular ameloblastic fibroma in a 6-year-old girl.

2008 - The use of tapered dental implants in severe jaw atrophies [Abstract in Rivista]
Bertossi, D.; Bissolotti, G.; Corrocher, G.; Anesi, Alexandre; Nocini, P. F.

Objective: To evaluate the use of tapered implants in combination with piezosurgical split-crest technique in severe atrophy of jaws. Methods: We selected 10 patients (age 45−58) presenting grade 4 to 5 class by Cawood and Howell of jaws. Those underwent piezosurgical split-crest technique and simultaneous tapered implants surgery. Pre-operative x-ray evaluation included standard x-panoramic and CT Dental-scan. Standard chemoprophylaxis was administered to each patient. The piezosurgical split-crest procedure was combined with alloplastic bone substitutes and double-layer membrane to improve the thickness of alveolar bone and simultaneous implant surgery. Every patient received from 3 to 6 with tapered screws which diameter was 3.75 mm and length 10−11.5 at 3 months from the first procedure. Results: Patients were monitored clinically and marginal bone changes were calculated utilizing periapical radiographs taken at placement and at subsequent appointments utilizing a standardized paralleling device and a 1-mm measurement grid for marginal bone remodeling at baseline and after 3 months within loading. Cumulative implant survival was 98.4% (n = 65). Mean marginal bone resorption (SD) was 1.19 (1.01) mm for the early loading group after 1 year. The use of tapered implants seem to reduce peak stress in both cortical and trabecular bone. Discussion: the use of tapered implants was revealed ideal in patients presenting atrophy of jaws. The taped designs show an ability to dissipate the interfacial stresses of bone, therefore improving the stability and the osteointegration if used in association to split crest made with piezosurgical device.

2006 - Gli osteotomi in chirurgia pre-protesica -Parte II [Articolo su rivista]
Baldisserri, E.; De Santis, D.; Malchiodi, L.; Ferrari, F.; Ruscitti, F.; Guarnieri, B.; Anesi, Alexandre

Dalle prime esperienze di Boyne, la rigenrazione ossea guidata (GBR) è diventata metodica indicata per la riabilitazione implantare nelle aree edentule ed atrofiche. Su questo fronte il continuo impegno di clinici, ricercatori ed industrie specializzate ha contribuito allo sviluppo di biomateriali e metodiche operative che forniscono al paziente standard elevati di qualità ed affidabilità dei processi produttivi.

2006 - I biomateriali per la rigenerazione ossea - Parte II [Articolo su rivista]
De Santis, D.; Baldisserri, E.; Anesi, Alexandre; Baltieri, A.; Fior, A.; Guarnieri, B; Ruscitti, F.

Dalle prime esperienze di Boyne, la rigenrazione ossea guidata (GBR) è diventata metodica indicata per la riabilitazione implantare nelle aree edentule ed atrofiche. Su questo fronte il continuo impegno di clinici, ricercatori ed industrie specializzate ha contribuito allo sviluppo di biomateriali e metodiche operative che forniscono al paziente standard elevati di qualità ed affidabilità dei processi produttivi.

2005 - Bi-lateral pneumothorax after orthognatic surgery. [Abstract in Rivista]
Bertossi, D.; Vismara, G.; Baltieri, A.; Toffanetti, F.; Furlani, M.; Anesi, Alexandre; Gottin, L.

Surgical problems as consequences of orthognatic surgery can be: upper airway impairment, hemorrage, infections, mobility of the splitted bones, nervous lesions. It is extremely rare to observe sub-cutaneous henfisema in association to bi-lateral pneumothorax. A 28 yrs. female, clinical history and instrumental evaluation negative for metabolic andclinical pathologies. She was treated with a Le Fort I osteotomy and BSSO sec. Gotte. Pre-surgical difficulties of the endonasal intubation with consequent bleeding. Intrasurgical left bleeding diring BSSO from the retromolas venous vessel.lntermaxillary fixation. The patient was transfered in Intensive Care Unit for 24 hours. Back to our Department at 12.00 am clinically well stabilized. At 4 pm sudden dispnea associated to moderate henfisema of the cheek and periorbital area. At 6 pm severe and sudden decrease of arterious saturation, patient conffused, increase of the henfisema that is now extended to the neck and the upper third of the anterior thorax. Immediate tranfer to the intensive care unit. Removal of IMF, oral intubation, a thorax xray shows right tension pneumothorax, that is treated with an intercostal drain. A thorax xray after 4 hours and a TC show a controlateral pneumothorax. This is treated with an intercostal drain. Both drainages are kept in site for 18 days. No further consequences. No neurological sequelae, no infections, no other osteotomies sequelae. Thorax henfisema after orthognatic sugery is extremely rare and is reported as a progression of high pressure air penetration through the deep fascia of the neck. So for tension pneumothorax complicated with a bi-lateral pneumothorax that was secondary to the henfisema. Sudden post-surgical dispnea associated to sub-cutaneous henfisema of the neck and of the thorax must be adequately observed with the aim of monitoring further severe sequelae. The anaesthetic management of the emergency difficult airway in any post-surgical orthognatic treatment can be extremely difficult requiring a carefully planned multi-disciplinary approach.

2005 - Gli osteotomi in chirurgia preprotesica -Parte I [Articolo su rivista]
Baldisserri, E.; de Santis, D.; Malchiodi, L.; Ferrari, F.; Ruscitti, F.; Guarnieri, B.; Anesi, Alexandre

Gli osteotomi in chirurgia orale sono utiizzati nel mini rialzo di seno mascellare secondo la tecnica du Summers, quando abbiamo un'altezza ossea alveolare di 8-10 mm ed uno spessore di cresta superiore ai 5 mm. Se lo spessore della cresta è inferiore ai 5 mm al mini rilazo va aggiunto uno split crest del processo alveolare sempre mediante osteotomi. In entrambi i casi descritti sopra gli impianti vengono posizionati in unico tempo chirurgico (immediati).

2005 - I biomateriali per la rigenerazione ossea -Parte I [Articolo su rivista]
De Santis, D.; Baldisserri, E.; Anesi, Alexandre; Procacci, P.; Ferrari, F.; Guarnieri, B.; Ruscitti, F.

Dalle prime esperienze di Boyne, la rigenrazione ossea guidata (GBR) è diventata metodica indicata per la riabilitazione implantare nelle aree edentule ed atrofiche. Su questo fronte il continuo impegno di clinici, ricercatori ed industrie specializzate ha contribuito allo sviluppo di biomateriali e metodiche operative che forniscono al paziente standard elevati di qualità ed affidabilità dei processi produttivi.