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Background & Aims: Direct-acting antivirals (DAAs) have dramatically improved the outcome of patients with hepatitis C virus (HCV) infection including those with decompensated cirrhosis (DC). We analyzed the evolution of indications and results of liver transplantation (LT) in the past 10 years in Europe, focusing on the changes induced by the advent of DAAs., Methods: This is a cohort study based on data from the European Liver Transplant Registry (ELTR). Data of adult LTs performed between January 2007 to June 2017 for HCV, hepatitis B virus (HBV), alcohol (EtOH) and non-alcoholic steatohepatitis (NASH) were analyzed. The period was divided into different eras: interferon (IFN/RBV; 2007-2010), protease inhibitor (PI; 2011-2013) and second generation DAA (DAA; 2014-June 2017)., Results: Out of a total number of 60,527 LTs, 36,382 were performed in patients with HCV, HBV, EtOH and NASH. The percentage of LTs due to HCV-related liver disease varied significantly over time (p <0.0001), decreasing from 22.8% in the IFN/RBV era to 17.4% in the DAA era, while those performed for NASH increased significantly (p <0.0001). In the DAA era, the percentage of LTs for HCV decreased significantly (p <0.0001) from 21.1% (first semester 2014) to 10.6% (first semester 2017). This decline was more evident in patients with DC (HCV-DC, -58.0%) than in those with hepatocellular carcinoma (HCC) associated with HCV (HCV-HCC, -41.2%). Conversely, three-year survival of LT recipients with HCV-related liver disease improved from 65.1% in the IFN/RBV era to 76.9% in the DAA era, and is now comparable to the survival of recipients with HBV infection (p = 0.3807)., Conclusions: In Europe, the number of LTs due to HCV infection is rapidly declining for both HCV-DC and HCV-HCC indications and post-LT survival has dramatically improved over the last three years. This is the first comprehensive study of the overall impact of DAA treatment for HCV on liver transplantation in Europe., Lay Summary: After the advent of direct-acting antivirals in 2014, a dramatic decline was observed in the number of liver transplants performed both in patients with decompensated cirrhosis due to hepatitis C virus (HCV), minus 60%, and in those with hepatocellular carcinoma associated with HCV, minus 41%. Furthermore, this is the first large-scale study demonstrating that the survival of liver transplant recipients with HCV-related liver disease has dramatically improved over the last three years and is now comparable to the survival of recipients with hepatitis B virus infection. The reduction in HCV-related indications for LT means that there is a greater availability of livers, at least 600 every year, which can be allocated to patients with indications other than HCV., (Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.)

The use of laparoscopic liver resection (LLR) has progressively spread in the last 10 years. Several studies have shown the superiority of LLR to open liver resection (OLR) in term of perioperative outcomes. With this review, we aim to systematically assess short-term and long-term major outcomes in patients who underwent LLR for hepatocellular carcinoma (HCC) in order to illustrate the advantages of minimally invasive liver surgery. Through an advanced PubMed research, we selected all retrospective, prospective, and comparative clinical trials reporting short-term and long-term outcomes of any series of patients with diagnosis of HCC who underwent laparoscopic or robotic resection. Reviews, meta-analyses, or case reports were excluded. None of the patients included in this review has received a previous locoregional treatment for the same tumor nor has undergone a laparoscopic-assisted procedure. We considered morbidity and mortality for evaluation of major short-term outcomes, and overall survival (OS) and disease-free survival (DFS) for evaluation of long-term outcomes. A total of 1,501 patients from 17 retrospective studies were included, 15 studies compare LLR with OLR. Propensity-score matching (PSM) analysis was used in 11 studies (975 patients). The majority of the studies included patients with good liver function and a single HCC. Cirrhosis at pathology ranged from 33% to 100%. Overall mortality and morbidity ranges were 0-2.4% and 4.9-44% respectively, with most of the complications being Clavien-Dindo grade I or II (range: 3.9-23.3% vs . 0-9.52% for Clavien I-II and ≥ III respectively). The median blood loss ranged from 150 to 389 mL; the range of the median duration of surgery was 134-343 minutes. The maximum rate of conversion was 18.2%. The median duration of hospitalization ranged from 4 to 13 days. The ranges of overall survival rates at 1-, 3- and 5-year were 72.8-100%, 60.7-93.5% and 38-89.7% respectively. The ranges of disease free survival rates at 1-, 3- and 5-year were 45.5-91.5%, 20-72.2% and 19-67.8% respectively. The benefits of LLR in term of complication rate, blood loss, and duration of hospital stay make this procedure an advantageous alternative to OLR, especially for cirrhotic patients in whom the use of LLR reduces the risk of post-hepatectomy liver failure. The limits of LLR can be overcome by robotic surgery, which could therefore be preferred. Further benefits of minimally invasive surgery derive from its ability to reduce the formation of adhesions in view of a salvage liver transplant. In conclusion, the results of this review seem to confirm the safety and feasibility of LLR for HCC as well as its superiority to OLR according to perioperative outcomes., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Introduction: The aim of this study is to analyze the evolution of pancreatectomy with venous resection in 10 referral Italian centers in the last 25 years., Methods: A multicenter database of 425 patients submitted to pancreatectomy with venous resection between 1991 and 2015 was retrospectively analyzed. Patients were classified in 5 periods: 1 (1991-1995); 2 (1996-2000); 3 (2001-2005); 4 (2006-2010); 5 (2011-2015). Indications and outcomes were compared according to the period of surgery., Results: Nineteen patients were operated in period 1, 28 in period 2, 91 in period 3, 140 in period 4, and 147 in period 5. Use of neoadjuvant therapy increased from 0% in period 1 and 2-12.1% in period 5. Postoperative complications ranged from 46.3% to 67.8%, and mortality from 5.3% to 9.2%. Median survival progressively increased, from 6 months in period 1-16 months in period 2, 24 months in period 3 and 4 and 35 months in period 5 (p = 0.004). Period, venous and nodal invasion were significant prognostic factors for survival., Conclusion: Management and outcomes of pancreatectomy with venous resection have evolved in the last 25 years in Italy. Improvement in patients' multidisciplinary management has lead to significant improvement of median survival., (Copyright © 2018. Published by Elsevier Ltd.)

Background: Transplantable hepatocellular carcinoma (HCC) represents a highly debated issue due to the overlap between indications for liver resection (LR) and transplantation (LT) in patients suitable for both., Study Design: Between January 2000 and December 2012, five hundred and twenty-four transplantable patients affected by HCC were identified among resected patients. Two regression models were constructed to classify patients into 2 groups pre-low and pre-high risk based on preoperative variables and then to reclassify pre-low-risk patients according to postoperative variables into either post-low or post-high-risk. Additionally, a cohort of patients with comparable baseline characteristics who underwent LT were similarly classified into pre-low and pre-high-risk groups and compared with the resected patients in terms of survival., Results: Cirrhosis, aspartate transaminase, α-fetoprotein, Model for End-Stage Liver Disease score, number of nodules, and diameter of the largest nodule were preoperatively found to be significantly related to overall survival post-LR. Microvascular invasion and satellites were selected to reclassify prognosis in the resulting preoperative low-risk group into post-high risk. The converted group (post-high) demonstrated the same 5-year survival as the pre-high group. Patients undergoing LT had better survival overall than those undergoing LR, with the exception of pre-low LT and post-low LR (confirmed low-risk LR) who had similar outcomes., Conclusions: The new models were strongly predictive of patients' likelihood of survival after LR for HCC on liver cirrhosis. Liver transplantation offers a survival advantage over LR, except in low-risk groups where both modalities might be comparable., (Copyright © 2018 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Islet transplantation has been reported to restore normoglycemia and the overall metabolic control in type 1 diabetes mellitus (DM). In the most experienced centers, islet transplantation clinical outcome is similar to that of the whole pancreas transplantation. Long-term islet transplantation function remains a very interesting matter worth discussing. A progressive islet function decrease was reported, probably due to islet exhaustion. In 5 islet-transplanted patients with at least 3-yr follow-up and still insulin independent, their glycemic control was characterized by a blinded retrospective continuous glucose monitoring system (CGMS). Islet transplantation restored glycemic control and glucose variability. Data were compared with patients in the waiting list. All the parameters of glycemic variability tested had improved significantly in patients who had islet transplantation compared with those patients who were on the waiting list. In conclusion, islet transplantation is able to maintain a proper glucose control and normalize glycemic variability in selected patients. A blinded retrospective CGMS is a useful method to characterize glucose homeostasis deeply in vivo in islet-transplanted patients.

Background: Prophylaxis of hepatitis B after liver transplantation with antiviral(s) and immunoglobulins efficiently protect the majority of recipients; however recent experiences suggest a decline of HBsAg-positive candidates and the use of hepatitis B Immunoglobulin-free schedules., Methods: This national survey evaluated the epidemiology and clinical results of hepatitis B prophylaxis among 10,365 liver transplants performed in 25 years in 13 Italian centers., Results: With a percentage of 22, 2260 procedures were performed in HBsAg-positive recipients and 714 out of 1080 anti-HBc-positive grafts were used in HBsAg-negative recipients; a total of 2974 patients (29%) were considered at risk of hepatitis B after liver transplantation. Similar rates (18% of HBsAg-positive candidates and 15% of anti-HBc-positive grafts) were registered in the last collected year. Combined prophylaxis with Hepatitis B Immunoglobulins remained prevalent among centers and was effective in 96% of HBsAg-positive recipients and in 94% of HBsAg-negative recipients of anti-HBc-positive grafts., Conclusions: Data from this survey confirm: the excellent results of combined prophylaxis; the past and persistent use of Hepatitis B Immunoglobulin-on and only rare -off prophylactic regimens, in contrast with the newest reports; the increasing use of anti-HBc-positive grafts; the past and present high prevalence of HBsAg-positive recipients, due to an increase in candidates with either hepatocellular carcinoma and Hepatitis Delta Virus coinfection in the last years.

Objective: Alternative sites to the liver for islet transplantation have been studied for a long time. Intramuscular islet transplantation appears to be an alternative site to the liver because of the ease of access. First islet autotransplantations were reported in patients after total pancreatectomies. The transplanted islets showed a proper revascularization and their function was observed for up to 2 years after the implant. However, only a few cases of autotransplantation and no allotransplantation have been performed. The aim of this study was to verify the feasibility of islet allotransplantation into muscles., Patients and Methods: In four patients affected by type 1 diabetes mellitus in which liver islet allotransplantation was contraindicated, human islets were transplanted into patients' arm muscle with local anesthesia., Results: The surgery was minimally invasive, without complications. In one patient a moderate local inflammatory reaction was observed at the site of the implant, which resolved spontaneously within 4 days. Islet graft function was observed after transplantation in all patients, but it progressively disappeared in 3 out 4 patients within a short time., Conclusions: In this first ever-reported intramuscular pancreatic islet allotransplantation, the procedure appears feasible but new strategies must be envisaged to significantly improve islet engraftment and the long-term graft function.

Background: The impact of the Pringle maneuver (PM) on long-term outcome after curative resection for hepatocellular carcinoma (HCC) is controversial, with eastern series reporting conflicting results. We aim to evaluate the impact of the PM in a western cohort., Methods: We retrospectively analyzed patients with HCC who underwent liver resection between January 2001 and August 2015. Patients were divided in two groups based the use of the PM during resection. Primary outcomes were overall survival (OS) and disease-free survival (DFS)., Results: A total of 441 patients were analyzed. Of these, 176 patients (39.9%) underwent PM. Median OS was 46.4 months (95%CI: 34.1-58.7) for the PM group and 56.5 months (95%CI: 37.1-75.9) for the no-PM group (P = 0.188), with a median DFS of 26.7 months (95%CI: 15.7-37.7) and 24.9 months (95%CI: 18.1-31.7), respectively (P = 0.883)., Conclusions: These results suggest that PM does not increase the risk of tumor recurrence or decrease long-term survival., (© 2017 Wiley Periodicals, Inc.)

Background & Aims: Outcomes of liver transplantation for hepatocellular carcinoma (HCC) are determined by cancer-related and non-related events. Treatments for hepatitis C virus infection have reduced non-cancer events among patients receiving liver transplants, so reducing HCC-related death might be an actionable end point. We performed a competing-risk analysis to evaluate factors associated with survival of patients with HCC and developed a prognostic model based on features of HCC patients before liver transplantation., Methods: We performed multivariable competing-risk regression analysis to identify factors associated with HCC-specific death of patients who underwent liver transplantation. The training set comprised 1018 patients who underwent liver transplantation for HCC from January 2000 through December 2013 at 3 tertiary centers in Italy. The validation set comprised 341 consecutive patients who underwent liver transplantation for HCC during the same period at the Liver Cancer Institute in Shanghai, China. We collected pretransplantation data on etiology of liver disease, number and size of tumors, patient level of α-fetoprotein (AFP), model for end-stage liver disease score, tumor stage, numbers and types of treatment, response to treatments, tumor grade, microvascular invasion, dates, and causes of death. Death was defined as HCC-specific when related to HCC recurrence after transplantation, disseminated extra- and/or intrahepatic tumor relapse and worsened liver function in presence of tumor spread. The cumulative incidence of death was segregated for hepatitis C virus status., Results: In the competing-risk regression, the sum of tumor number and size and of log 10 level of AFP were significantly associated with HCC-specific death (P < .001), returning an average c-statistic of 0.780 (95% confidence interval, 0.763-0.798). Five-year cumulative incidence of non-HCC-related death was 8.6% in HCV-negative patients and 18.1% in HCV-positive patients. For patients with HCC to have a 70% chance of HCC-specific survival 5 years after transplantation, their level of AFP should be <200 ng/mL and the sum of number and size of tumors (in centimeters) should not exceed 7; if the level of AFP was 200-400 ng/mL, the sum of the number and size of tumors should be ≤5; if their level of AFP was 400-1000 ng/mL, the sum of the number and size of tumors should be ≤4. In the validation set, the model identified patients who survived 5 years after liver transplantation with 0.721 accuracy (95% confidence interval, 0.648%-0.793%). Our model, based on patients' level of AFP and HCC number and size, outperformed the Milan; University of California, San Francisco; Shanghai-Fudan; Up-to-7 criteria (P < .001); and AFP French model (P = .044) to predict which patients will survive for 5 years after liver transplantation., Conclusions: We developed a model based on level of AFP, tumor size, and tumor number, to determine risk of death from HCC-related factors after liver transplantation. This model might be used to select end points and refine selection criteria for liver transplantation for patients with HCC. To predict 5-year survival and risk of HCC-related death using an online calculator, please see www.hcc-olt-metroticket.org/. ClinicalTrials.gov ID NCT02898415., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Selection of the right or left living donor kidney for transplantation is influenced by many variables. In the present multi centric study including 21 Italian transplant centres, we evaluated whether centre volume or surgical technique may influence the selection process., Methods: Intra- and perioperative donor data, donor kidney function, and recipient and graft survival were collected among 693 mini-invasive living donor nephrectomies performed from 2002 to 2014. Centre volume (LOW, 1-50 cases; HIGH, >50 cases) and surgical technique (FULL-LAP, full laparoscopic and robotic; HA-LAP, hand-assisted laparoscopy; MINI-OPEN, mini-lumbotomy) were correlated with selection of right or left donor kidney and with donor and recipient outcome., Results: HIGH-volume centres retrieved a higher rate of donor right kidneys (29.3% versus 17.6%, P < 0.01) with single artery (83.1% versus 76.4%, P < 0.05) compared with LOW-volume centres. Surgical technique correlated significantly with rate of donor right kidney and presence of multiple arteries: MINI-OPEN (53% and 13%) versus HA-LAP (29% and 22%) versus FULL-LAP (11% and 23%), P < 0.001 and P < 0.05, respectively. All donors had an uneventful outcome; donor bleeding was more frequent in LOW-volume centres (4% versus 0.9%, P < 0.05)., Conclusions: Centre volume and surgical technique influenced donor kidney side selection. Donor nephrectomy in LOW-volume centres was associated with higher risk of donor bleeding., (© The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Split-liver transplantation has been proposed as an alternative to whole liver (WL) transplantation to expand the donor pool, but studies comparing adult longterm outcomes between the 2 methods are conflicting and limited. This is the first Italian multicenter study that retrospectively analyzed 119 matched-pair recipients of whole and extended right grafts (ERGs) for longterm survival outcomes. In the overall population, WL recipients showed higher patient survival at 1 (93% versus 73%), 5 (87% versus 65%), and 10 years (83% versus 60%) after transplantation compared with split-liver recipients (P < 0.001); graft survivals of WL recipients were also superior at 1 (90% versus 76%), 5 (84% versus 57%), and 10 years (81% versus 52%) posttransplant (P < 0.001). However, among the 81 matched pairs that survived the first posttransplant year, 5- and 10-year patient survivals were 90% and 81% for split recipients and 99% and 96% for whole recipients, respectively (P = 0.34). The 5- and 10-year graft survivals were also comparable: 87% and 77% for split recipients, and 86% and 82% for whole recipients (P = 0.86). Cox regression analysis identified donor age >50, donor-to-recipient weight ratio < 1, retransplantation status, and United Network for Organ Sharing I-IIA status as risk factors for partial graft use. There were no significant differences in 5-year outcomes based on center volume. In conclusion, we demonstrate that adult liver transplantation with ERGs can achieve longterm success comparable with that of whole grafts in appropriate patients but should be selectively used in patients with risk factors. Liver Transplantation 23 1384-1395 2017 AASLD., (© 2017 by the American Association for the Study of Liver Diseases.)

Background: The role of drug-resistance infections on surgical outcomes is controversial. The aim of the study was to determine whether increase antibiotic resistance was an independent risk factor for development of major non-infectious postoperative complications., Methods: This work included a multicenter cohort study of patients who underwent pancreatic resections for cancer over a 3-year interval. The primary outcome was major non-infectious complication rate developing after the occurrence of multi-drug sensitive (MDS) infection, multi-drug-resistant infection (MDR), and extensive drug-resistant (XDR) infection. Multivariate logistic regression models were used to adjust for patient and operative effects., Results: Eligible patients (517) were selected for the analysis. One hundred and thirteen (21.8%) patients had major non-infectious complications with a rate of 12.9% in the no infection group, 29.3% in the MSD, 41.5% in the MDR, and 58.8% in the XDR (p < 0.001). The median time of infection occurrence was postoperative days 4 (2-7 IQR) and 7 (3-12 IQR) non-infectious complications. At multivariate analysis, the risk of having major non-infectious complications was 2.67 (95% CI 1.24-5.77, P = 0.012) for MDR, 5.04 (95% CI 2.35-10.80, P < 0.001) for MDR, and 9.64 (95% CI 2.71-34.28, P < 0.001) for XDR., Conclusion: Antimicrobial resistance is significantly associated with the risk of major non-infectious morbidity.

Background: The purpose of the study was to evaluate whether the mutational status of Kirsten rat sarcoma viral oncogene homolog (KRAS) or b-viral oncogene homolog B1 (BRAF) could be an independent prognostic factor in the subset of patients with colorectal cancer liver metastases (CRLM) who undergo complete liver resection., Materials and Methods: A systematic literature review was performed to identify articles reporting relapse-free survival (RFS) and/or overall survival (OS) of patients who underwent complete liver resection for CRLM, stratified according to KRAS and BRAF mutational status. Hazard ratios (HRs) from multivariate analyses were pooled in the meta-analysis., Results: Eleven studies, including 1833 patients, were eligible for the meta-analysis. Nine of them reported OS stratified according to KRAS mutation. The pooled analysis revealed that KRAS mutation was negatively associated with OS (HR, 1.674; 95% confidence interval [CI], 1.341-2.089; P < .001). Nine among 11 studies reported RFS stratified according to KRAS mutation and HRs in multivariate analysis were available in 7. In a pooled analysis, KRAS mutation was negatively associated with RFS (HR, 1.529; 95% CI, 1.287-1.817; P < .001). In 3 studies HRs of the multivariate analysis regarding the OS according to BRAF mutational status were also available, showing a negative association with OS (HR, 3.055; 95% CI, 1.794-5.204; P < .001)., Conclusion: KRAS mutations are negatively associated with OS and RFS in patients who undergo complete liver resection for CRLM. A similar negative effect on OS was observed also for BRAF mutation, although fewer studies were included. These data support integration of KRAS and BRAF mutational status into a combined predictive score for prospective assessment of outcome after resection of CRLM in clinical studies., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The place of liver transplantation in the treatment of severe iatrogenic liver injuries has not yet been widely discussed in the literature. Bile duct injuries during cholecystectomy represent the leading cause of liver transplantation in this setting, while other indications after abdominal surgery are less common. Urgent liver transplantation for the treatment of severe iatrogenic liver injury may-represent a surgical challenge requiring technically difficult and time consuming procedures. A debate is ongoing on the need for centralization of complex surgery in tertiary referral centers. The early referral of patients with severe iatrogenic liver injuries to a tertiary center with experienced hepato-pancreato-biliary and transplant surgery has emerged as the best treatment of care. Despite widespread interest in the use of liver transplantation as a treatment option for severe iatrogenic injuries, reported experiences indicate few liver transplants are performed. This review analyzes the literature on liver transplantation after hepatic injury and discusses our own experience along with surgical advances and future prospects in this uncommon transplant setting., Competing Interests: Conflict-of-interest statement: No conflict of interest to declare.

The main goal of allocation system is to guarantee an equal access to the limited resource of liver grafts for every class of patients on the waiting list, balancing between the ethical principles of equity, utility, benefit, need, and fairness. The aim of this review was to analyze liver allocation policies among these organizations, focusing on HCC. The European area considered for this analysis included 6 macro-areas or countries, which are congregated from the same policy of liver sharing and allocation. By this definition, the 6 areas identified are: Centro Nazionale Trapianti (CNT) in Italy; Eurotransplant (Germany, the Netherlands, Belgium, Luxembourg, Austria, Hungary, Slovenia, and Croatia); Organizacion Nacional de Transplantes (ONT) in Spain; Etablissement francais des Greffes (EfG) in France; NHS Blood Transplant (NHSBT) in the United Kingdom and Ireland; Scandiatransplant (Sweden, Norway, Finland, Denmark, and Iceland); Romanian National Policy. Each identified area, as network for organ sharing in Europe, adopts a basic allocation system that consider a policy center oriented or patient oriented. Priorization of patients affected by HCC in the waiting list for deceased donors liver transplant worldwide is dominated by 2 main principles: urgency and utility. The main message of this review is the absence of a common organs allocation policy over the Eurpean countries. Despite that, long-term survival of the community of patients listed for transplant due to HCC results, however, highly acceptable in Europe and comparable to the long-term survial reported in the UNOS register., (Celsius.)

Introduction: Robot-assisted kidney harvesting from living donors is feasible and safe. We report the results of a mono-centric experience relative to 98 consecutive robotic nephrectomies with emphasis on global donor complications., Materials and Methods: This is a retrospective cohort study. Donors underwent robot-assisted kidney harvesting. The preferred kidney was the left one even in the presence of vascular anomalies. In the first cases we used a robotic hand-assisted technique, then the totally robotic technique, and finally the modified totally robot-assisted technique. Postoperative complications were ranked according to the five-grade Clavien-Dindo classification., Results: Between November 2009 and November 2016, 98 living donors underwent nephrectomy. We experienced 14 complications. The 3 intraoperative ones (3.06%) were 1 pneumothorax and 2 acute bleedings, 1 of them requiring transfusion. The 11 postoperative complications (11.22%) were as follows: 5 wound seromas, 1 rhabdomyolisis (Clavien I), 1 paretic ileum, 1 anemia requiring transfusion, 1 hypertensive crisis (Clavien II), and 2 chylus collections drained by interventional radiologists (Clavien III). Transfusion rate was 2.1%; conversions, reoperations, and mortality were nil. No statistically significant difference was observed between the patients with complications and without in terms of gender, age, anatomical anomalies, body mass index (BMI), and learning curve. We observed a longer global operation length of time in patients with complications., Conclusion: Robotic assistance results in shorter and simpler learning curves for the harvesting of kidneys from living donors. It enables an easier and more efficient management of possible intraoperative complications. The rate of postoperative complications is comparable with the rate of complications encountered in traditional laparoscopic series with high numbers of harvestings., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The role of donation after cardiac death (DCD) in expanding the donor pool is mainly limited by the incidence of primary nonfunction (PNF) and ischemia-related complications. Even greater concern exists toward uncontrolled DCD, which represents the largest potential pool of DCD donors. We recently started the first Italian series of DCD liver transplantation, using normothermic regional perfusion (NRP) in 6 uncontrolled donors and in 1 controlled case to deal with the legally required no-touch period of 20 minutes. We examined our first 7 cases for the incidence of PNF, early graft dysfunction, and biliary complications. Acceptance of the graft was based on the trend of serum transaminase and lactate during NRP, the macroscopic appearance, and the liver biopsy. Hypothermic machine perfusion (HMP) was associated in selected cases to improve cold storage. Most notably, no cases of PNF were observed. Median posttransplant transaminase peak was 1014 IU/L (range, 393-3268 IU/L). Patient and graft survival were both 100% after a mean follow-up of 6.1 months (range, 3-9 months). No cases of ischemic cholangiopathy occurred during the follow-up. Only 1 anastomotic stricture completely resolved with endoscopic stenting. In conclusion, DCD liver transplantation is feasible in Italy despite the protracted no-touch period. The use of NRP and HMP seems to earn good graft function and proves safe in these organs. Liver Transplantation 23 166-173 2017 AASLD., (© 2016 by the American Association for the Study of Liver Diseases.)

Major concerns about donor morbidity and mortality still limit the use of living donor liver transplantation (LDLT) to overcome the organ shortage. The present study assessed donor safety in LDLT in Italy reporting donor postoperative outcomes in 246 living donation procedures performed by 7 transplant centers. Outcomes were evaluated over 2 time periods using the validated Clavien 5-tier grading system, and several clinical variables were analyzed to determine the risk factors for donor morbidity. Different grafts were obtained from the 246 donor procedures (220 right lobe, 10 left lobe, and 16 left lateral segments). The median follow-up after donation was 112 months. There was no donor mortality. One or more complications occurred in 82 (33.3%) donors, and 3 of them had intraoperative complications (1.2%). Regardless of graft type, the rate of major complications (grade ≥ 3) was 12.6% (31/246). The overall donor morbidity and the rate of major complications did not differ significantly over time: 26 (10.6%) donors required hospital readmission throughout the follow-up period, whereas 5 (2.0%) donors required reoperation. Prolonged operative time (>400 minutes), intraoperative hypotension (systolic < 100 mm Hg), vascular abnormalities, and intraoperative blood loss (>300 mL) were multivariate risk factors for postoperative donor complications. In conclusion, from the standpoint of living donor surgery, a meticulous and well-standardized technique that reduces operative time and prevents blood loss and intraoperative hypotension may reduce the incidence of donor complications. Transparency in reporting results after LDLT is mandatory, and we should continue to strive for zero donor mortality. Liver Transplantation 23 184-193 2017 AASLD., (© 2016 by the American Association for the Study of Liver Diseases.)

Immunosuppression after liver transplantation (LT) is presently based on use of calcineurin inhibitors (CNI), although they are associated with an increased incidence of renal dysfunction, cardiovascular complications, and de novo and recurrent malignancies. Over the past decade, mammalian target of rapamycin inhibitors have received considerable attention as immunosuppressants because they are associated with a more favorable renal profile versus CNI, as well as antiproliferative activity in clinical studies. Comprehensive guidelines on use of everolimus (EVR) in LT are still lacking. In Italy, a project, named Everolimus: the road to long-term functioning, was initiated to collect the experience on EVR after LT with the aim of providing guidance for transplant clinicians. Herein, recommendations by this national consensus group, based on Delphi methodology, are presented. Consensus was reached on 20 of the 23 statements proposed, and their level of evidence, grade of recommendation, and percent of agreement are reported. Statements are grouped into 4 areas: (A) renal function; (B) time of EVR introduction, CNI reduction and elimination, and risk for graft rejection; (C) antiproliferative effects of EVR; and (D) management of EVR-related adverse events. The high level of consensus shows that there is good agreement on the routine use of EVR in predefined clinical scenarios, especially in light of posttransplant nephrotoxicity and other adverse events associated with long-term administration of CNIs., Competing Interests: P.D.S. has served as advisor and has received speaker’s fees from Novartis. The other authors declare no conflicts of interest.

The main goal of organ allocation systems is to guarantee an equal access to the limited resource of liver grafts for every patients on the waiting list, balancing between the ethical principles of equity, utility, benefit, need , and fairness. The European heath care scenario is very complex, as it is essentially decentralized and each Nation and Regions inside the nation, operate on a significant degree of autonomy. Furthermore the epidemiology of liver diseases and HCC, which is different among European countries, clearly inpacts on indications and priorities. The aims of this review are to analyze liver allocation policies for hepatocellular carcinoma, among different European. The European area considered for this analysis included 5 macro-areas or countries, which have similar policies for liver sharing and allocation: Centro Nazionale Trapianti (CNT) in Italy; Eurotransplant (Germany, the Netherlands, Belgium, Luxembourg, Austria, Hungary, Slovenia, and Croatia); Organizacion Nacional de Transplantes (ONT) in Spain; Etablissement français des Greffes (EfG) in France; NHS Blood & Transplant (NHSBT) in the United Kingdom and Ireland; Scandiatransplant (Sweden, Norway, Finland, Denmark, and Iceland). Each identified area, as network for organ sharing in Europe, adopts an allocation system based either on a policy center oriented or on a policy patient oriented. Priorization of patients affected by HCC in the waiting list for deceased donors liver transplant worldwide is dominated by 2 main principles: urgency and utility. Despite the absence of a common organs allocation policy over the Eurpean countries, long-term survival patients listed for transplant due to HCC are comparable to the long-term survival reported in the UNOS register. However, as the principles of allocation are being re-discussed and new proposals emerge, and the epidemiology of liver disease changes, an effort toward a common system is highly advisable., Competing Interests: Conflict of Interest Mario Strazzabosco, Stefano Okolicsanyi, Vincenzo Buscemi, Leonardo Centonze, Luciano De Carlis, Riccardo De Carlis, Stefano Di Sandro, Fabio Ferla, Andrea Lauterio, Raffaella Sguinzi, and Luca Saverio Belli declare no conflict of interest. MS has received speaking honoraria from Bayer, None of the other authors have any conflict of interest, neither in terms of funding or of commercial associations.

Aim: To develop a prognostic scoring system for overall survival (OS) of patients undergoing liver resection (LR) for hepatocellular carcinoma (HCC)., Methods: Consecutive patients who underwent curative LR for HCC between 2000 and 2013 were identified. The series was randomly divided into a training and a validation set. A multivariable Cox model for OS was fitted to the training set. The beta coefficients derived from the Cox model were used to define a prognostic scoring system for OS. The survival stratification was then tested, and the prognostic scoring system was compared with the European Association for the Study of the Liver (EASL)/American Association for the Study of Liver Diseases (AASLD) surgical criteria by means of Harrell's C statistics., Results: A total of 917 patients were considered. Five variables independently correlated with post-LR survival: Model for End-stage Liver Disease score, hepatitis C virus infection, number of nodules, largest diameter and vascular invasion. Three risk classes were identified, and OS for the three risk classes was significantly different both in the training (P < 0.0001) and the validation set (P = 0.0002). Overall, 69.4% of patients were in the low-risk class, whereas only 37.8% were eligible to surgery according to EASL/AASLD. Survival of patients in the low-risk class was not significantly different compared with surgical indication for EASL/AASLD guidelines (77.2 mo vs 82.5 mo respectively, P = 0.22). Comparison of Harrell's C statistics revealed no significant difference in predictive power between the two systems (-0.00999, P = 0.667)., Conclusion: This study established a new prognostic scoring system that may stratify HCC patients suitable for surgery, expanding surgical eligibility with respect to EASL/AASLD criteria with no harm on survival., Competing Interests: Conflict-of-interest statement: No conflicts of interest are declared by the authors with respect to the material and methodology presented in the manuscript.

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

Background: As compared with traditional laparoscopy, robotic-assisted surgery provides better EndoWrist instruments and three-dimensional visualization of the operative field. Studies published so far indicate that living donor nephrectomy using the robot-assisted technique is safe, feasible, and provides remarkable advantages for the patients., Methods: From 5 papers reporting detailed descriptions of surgical technique for robotic assisted nephrectomy (RAN) in living donor kidney transplantation, we have gathered information about the surgical techniques as well as about patients' intra- and postoperative outcome. Data from these articles were analyzed together with the data from our own experience (33 cases) so that the total number of analyzed cases was 292., Results: In the analyzed populations, no case of donor death occurred, and no case developed complication above grade 2 of Clavien score. Perioperative complications occurred in 37 of the 292 patients (12.6%). Accidental acute hemorrhage occurred in 5 of the 292 cases (1.7%). The average overall intraoperative blood loss was 67.8 mL (range 10 to 1,500). The average warm ischemia time was 3.5 minutes (range .58 to 7.6). Conversion to the open technique occurred in only 4 cases (1.3%). The average overall operative time was 192 minutes (range 60 to 400). The average length of the hospital stay was 2.7 days (range 1 to 10)., Conclusions: Safety and feasibility of RAN are pointed out in all the reviewed article, both as hand-assisted and as totally robotic technique. RAN appears to be significantly easier for the surgeons and the results are comparable with the ones obtained with the pure laparoscopic technique., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The main purpose of this paper, written by a group of Italian expert transplant surgeons, is to provide clinical support and to help through the decision-making process over pre-transplant surgical procedures in potential kidney recipients, as well as selection of pancreas transplant candidates and perioperative management of kidney recipient. Current topics such as different approaches in minimally invasive donor nephrectomy, methods of graft preservation and treatment of failed allograft were addressed.

Background: Elderly donor livers are thought to be marginal graft. In the present study, we aimed to identify an age threshold to consider a graft as elderly to identify the trend (if any) of the donor age in our series and to identify an efficient allocation criteria for elderly grafts., Methods: We reviewed in a retrospective manner our series of 1520 liver transplants, comparing graft survival under and over a certain age. On the basis of the results of this analysis, we identified a threshold of 70 years to define a graft as old. The donor age trend analysis showed an increasing rate of transplants from elderly donors., Results: To identify efficient allocation criteria for elderly graft, we stratified the series by the disease of the recipient: 556 patients underwent transplants for hepatocellular carcinoma (HCC+ group) and 964 for other diseases (HCC- group). Two hundred twenty-one patients of 556 of the HCC+ group were hepatitis c virus (HCV) negative (HCC+/HCV- group), and 312 of 964 of the HCC- group were HCV positive (HCC-/HCV+). The survival analysis showed no significant differences in comparing the outcome for elderly and young grafts in the HCC+ (P = .135) and HCC- (P = .055) groups., Conclusions: When comparing the survival of old and young livers in the HCC+/HCV- group, the elderly livers appear to have a better outcome (P = .05); on the other hand, the same analysis in the HCC-/HCV+ group shows a worse outcome for old-aged grafts (P = .026). Therefore, the present study suggests that elderly livers should be allocated to hepatocellular carcinoma (HCC) patients and should be avoided in HCV+ recipients., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Dual kidney transplantation (DKT) is a largely accepted strategy to enlarge the donor pool. Niguarda Hospital started this program in December 2010, and 38 DKT have been performed. In our series, we included recipients older than those in the other series published in literature. The aim of this study was to know if our recipient selection criteria for DKT are safe., Methods: We reviewed our data base of DKT and analyzed recipients' medical history, surgical technique, post-operative complications, graft survival, morbidity, and mortality. We then compared our results with the literature., Results: From December 2010 to April 2015, 38 DKT were performed in Niguarda Hospital. Delayed graft function was present in 21 recipients. Explantation of both kidneys was performed in 1 patient and explantation of 1 kidney in 6 patients. Post-operative complications were present in 8 patients. Five patients returned to hemodialysis after DKT. One recipient died of medical post-operative sepsis. The mean follow-up was 24 months. Graft survival and patient survival were 86.84% and 97.93%, respectively. Compared with the literature, our series had similar mortality and morbidity rates, even if recipients' age was higher than in other series., Conclusions: The strategy of DKT allocation in elderly recipients is safe. Further studies have to be performed to optimized selection of the recipients for DKT not to disadvantage younger patients in the transplant waiting list and to improve the technique of organ evaluation and preservation to refine graft allocation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: Repeat hepatectomy (RH) is considered a valuable option for management of recurrent colorectal liver metastases (R-CLM). Here, the outcome of RH for R-CLM was compared to that of patients who underwent single hepatectomy (SH) after subdividing the later according to re-recurrence status., Methods: Between 2001 and 2013, patients who received hepatectomy for CLM and R-CLM were included in study. Patients with non-resectable R-CLM were excluded., Results: One hundred sixteen patients were included: 86 patients in SH group and 30 patients in RH group. Repeat hepatectomy group had more synchronous CLM (76.7 versus 50 %, p = 0.011). From the 86 patients who underwent SH, 69 patients did not have R-CLM. Survival analysis was done from the time of first hepatectomy for the no R-CLM group and the time of RH for the RH group. The 3- and 5-year survival rates for the no R-CLM group were 66.4 and 48.8%, respectively, and for the RH group were 56 and 44.8% respectively (p = 0.841). Multivariate analysis showed that larger size of R-CLM is an independent risk factor for survival after RH., Conclusion: Repeat hepatectomy for R-CLM shows a comparable OS to non-recurrent CLM after single hepatectomy, despite the RH group had higher incidence of synchronous CLM.

Growing experience with the liver splitting technique and favorable results equivalent to those of whole liver transplant have led to wider application of split liver transplantation (SLT) for adult and pediatric recipients in the last decade. Conversely, SLT for two adult recipients remains a challenging surgical procedure and outcomes have yet to improve. Differences in organ shortages together with religious and ethical issues related to cadaveric organ donation have had an impact on the worldwide distribution of SLT. Despite technical refinements and a better understanding of the complex liver anatomy, SLT remains a technically and logistically demanding surgical procedure. This article reviews the surgical and clinical advances in this field of liver transplantation focusing on the role of SLT and the issues that may lead a further expansion of this complex surgical procedure.

Background: Data are lacking regarding the long-term effect of preemptive conversion to everolimus from calcineurin inhibitors early after liver transplantation to avoid renal deterioration., Methods: In a prospective, multicenter, open-label study, de novo liver transplant patients were randomized at day 30 to (i) everolimus + reduced exposure tacrolimus (EVR + Reduced TAC), (ii) everolimus + tacrolimus elimination (TAC Elimination), or (iii) standard exposure tacrolimus (TAC Control)., Results: Randomization to TAC Elimination was terminated prematurely due to a higher rate of treated biopsy-proven acute rejection (tBPAR) during TAC withdrawal. Of 370 patients who completed the 24-month core study on-treatment, 282 (76.2%) entered an additional 12-month extension phase. The composite efficacy failure endpoint (tBPAR, graft loss or death) occurred in 11.5% of EVR+Reduced TAC patients versus 14.6% TAC Controls from randomization to month 36 (difference, -3.2%; 95% confidence interval, -10.5% to 4.2%; P = 0.334). Treated BPAR occurred in 4.8% versus 9.2% of patients (P = 0.076). From randomization to month 36, mean (SD) estimated glomerular filtration rate decreased by 7.0 (31.3) mL/min per 1.73 m in the EVR+Reduced TAC group, and 15.5 (22.7) mL/min per 1.73 m in the TAC Control group (P = 0.005). Rates of adverse events, serious adverse events, and discontinuation due to adverse events were similar in both groups during the extension., Conclusions: A clinically relevant renal benefit after introduction of everolimus with reduced-exposure tacrolimus at 1 month after liver transplantation was maintained to 3 years in patients who continued everolimus therapy to the end of the core study, with comparable efficacy and no late safety concerns.

Liver transplantation is the ideal treatment for patients affected by early stage hepatocellular carcinoma and chronic liver disease. Considering organs shortage, alternative treatments have to be adopted to minimize the waitlist drop-out, and in case of recurrence within the accepted criteria, salvage transplantation can be considered. Surgical resection is one of the most effective treatments, with the possibility of oncological radicality and pathological analysis of the specimen. Although these theoretical advantages, surgical strategy cannot be applied to all patients because of the impaired liver function as well as the amount of parenchyma to be resected does not allow a sufficient future liver remnant. Furthermore, resection by laparotomy may lead to strong intra-abdominal adhesions in a contest of portal hypertension and, as potential consequence, increase transplantation difficulty raising morbidity. Laparoscopic liver resection is now performed as a routine procedure in tertiary referral centers, with increasing evidence of long-term results comparable to traditional surgery together with the advantages of a minimally invasive approach. In addition, with a salvage transplantation strategy that has been shown to be comparable to primary transplantation, the patient can live with his native liver avoiding an invasive procedure and long-term immunosuppression, allowing the use of liver grafts for the community. We present the results of an Italian multicenter experience of salvage liver transplantation following the recurrence of HCC initially treated by laparoscopic resection in 31 patients, performed by four referral centers. Mean operative transplantation time was 450 min, morbidity was 41.9%, 90-days mortality was 3.2%, and median post-operative length of stay was 17.9 days. Salvage liver transplantation after laparoscopic liver resection for HCC is comparable to open surgery in terms of operative time, oncologic radicality, morbidity and mortality, with the advantages of laparoscopic surgery.

Background/aims: Selection of patients with hepa- to-cellular carcinoma for liver transplantation is gen- erally performed according to the so-called Milan cri- teria. The aim of this study was to learn whether, after down-staging loco-regional therapies, patients origi- nally non-fulfilling the MC (Milan-OUT) meet these criteria (Milan-IN)., Methodology: Between January 2000 and December 2008, 172 patients with HCC re- ceived LT at our Department. Of these, 142 were sub- jected to DS before LT., Results: Of the 142 patients who received DS, 115 (81%) were Milan-IN and 27 (19%) were Milan-OUT at the time of their enrollment in the waiting list for LT. After a median follow-up of 50 months, overall 1-, 3-, and 5-year survival and dis- ease recurrence-free survival were not significantly different., Conclusions: Patients with Milan-OUT HCC can be successfully subjected to LT when they fulfill the MC after being subjected to DS. Imaging progres- sion while on the waiting list is a strong predictor of high rates of HCC recurrence even in patients meet- ing the MC. Lack of imaging progression seems to be a strong predictor of positive LT outcome and should be added to the eligibility criteria for the assessment of LT candidates with HCC.

This survey provides an overview about current spread of Minimally Invasive Liver Resection (MILR) in Italy. Primary endpoint was to assess evolution of MILR in recent years and its degree of application among centres with different experience in laparoscopic and hepatic surgery. A questionnaire with items describing activity MILR was sent to Italian surgical centers. Diagnosis, technical approaches, resection extent, devices and vascular control, reasons for conversion, morbidity and mortality were recorded. Level of expertise per centre was analysed in terms of learning curve acquisition and relationship with hepatobiliary background. 1497 MILRs from 39 centers (median 27 patients/center, range 1-145, period 1995-2012) were collected. Conversion rate was 10.7% (180 patients out of 1677, excluded from subsequent analysis), with bleeding representing most frequent cause of conversion (34.4%). Eleven centers completed learning curve, performing >60 MILR. Benign lesions were 27.5% and malignant 72.5%, with hepatocellular carcinoma being the most frequent indication. 92.6% of cases were performed with a totally laparoscopic technique (1.3% were hand-assisted, 1.9% single-port and 4.2% robotic). Minor resections accounted for 92.9% (left lateral sectionectomy resulted the most frequent procedure; 23.8%), while major resections represented 7.1%. Overall mortality was 0.2% (3 of 1497 patients) and morbidity 22.8%. Mean length of stay was 5 days. Correlation between MILR activity and a hepatobiliary background was not clear comparing MILR cases and liver resection volumes per center. MILR has been significantly widespread in Italy in recent years, with several centers having definitely completed the learning curve as attested by clinical results consistent with major series from the Western and Eastern countries. MILR programs in Italy seem to arise from both centers with specific hepatobiliary expertise and centers performing advanced general laparoscopic surgery.

Aim: To evaluate the predictors of 10-year survival of patients with hepatitis C recurrence., Methods: Data from 358 patients transplanted between 1989 and 2010 in two Italian transplant centers and with evidence of hepatitis C recurrence were analyzed. A χ(2), Fisher's exact test and Kruskal Wallis' test were used for categorical and continuous variables, respectively. Survival analysis was performed at 10 years after transplant using the Kaplan-Meier method, and a log-rank test was used to compare groups. A P level less than 0.05 was considered significant for all tests. Multivariate analysis of the predictive role of different variables on 10-year survival was performed by a stepwise Cox logistic regression., Results: The ten-year survival of the entire population was 61.2%. Five groups of patients were identified according to the virological response or lack of a response to antiviral treatment and, among those who were not treated, according to the clinical status (mild hepatitis C recurrence, "too sick to be treated" and patients with comorbidities contraindicating the treatment). While the 10-year survival of treated and untreated patients was not different (59.1% vs 64.7%, P = 0.192), patients with a sustained virological response had a higher 10-year survival rate than both the "non-responders" (84.7% vs 39.8%, P < 0.0001) and too sick to be treated (84.7% vs 0%, P < 0.0001). Sustained virological responders had a survival rate comparable to patients untreated with mild recurrence (84.7% vs 89.3%). A sustained virological response and young donor age were independent predictors of 10-year survival., Conclusion: Sustained virological response significantly increased long-term survival. Awaiting the interferon-free regimen global availability, antiviral treatment might be questionable in selected subjects with mild hepatitis C recurrence.

In situ split liver extended right grafts (SL-ERGs) are still considered marginal grafts. Our aim was to verify this statement at the present time. From 1997 to 2011, a multicenter, retrospective study based on a prospective database was performed at 9 liver transplantation (LT) centers in northern Italy; it included 382 in situ SL-ERG transplants in adults. There were 358 primary LTs and 24 retransplantations (RETXs). The 1-, 3-, and 5-year overall graft survival rate for LT with in situ SL-ERGs were 73.5%, 63.3%, and 60.7%, respectively, from 1997 to 2004 and 83.5%, 80.3%, and 80.3%, respectively, thereafter (P=0.0001). A shorter total ischemia time and fewer RETX grafts were the main differences between the characteristics of the 2 periods. From 1997 to 2011, the 1-, 3-, and 5-year graft survival rates showed a significant difference between the 358 primary LT in situ SL-ERGs and the 24 RETX in situ SL-ERGs (P<0.001). In a multivariate analysis, the main prognostic factor for 60-day graft survival was a total ischemia time<8 hours for the 358 primary in situ SL-ERGs. From 2005 to 2011, in 2473 LTs, the 5-year graft survival for 184 in situ SL-ERGs and 2289 whole grafts was 75% and 80% (P=0.3), respectively. Univariate and multivariate studies alike failed to indicate that the type of graft was a prognostic factor for graft survival. A donor age>60 years, RETX grafts, and urgency were the main prognostic factors for failure for all of the grafts. Although caution should be taken regarding the choice of appropriate donors, in situ SL-ERGs should no longer be considered marginal grafts for experienced LT centers. SL-ERGs should not be used in RETX settings, and when SL-ERGs are used as primary grafts, the total ischemia time should be less than 8 hours., (© 2015 American Association for the Study of Liver Diseases.)

Twenty years since the first cases were described, adult living donor liver transplantation (ALDLT) is now considered a valid option to expand the donor pool in view of the ongoing shortage of organs and the high waiting list mortality rate. Despite the rapid evolution and acceptance of this complex process of donation and transplantation in clinical practice, the indications, outcome, ethical considerations and quality and safety aspects continue to evolve based on new data from large cohort studies. This article reviews the surgical and clinical advances in the field of liver transplantation, focusing on technical refinements and discussing the issues that may lead to a further expansion of this complex surgical procedure and the role of ALDLT.

Background/aims: Mutual interactions between portal vein and hepatic artery can be documented during hepatobiliary surgery. Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) is a recently introduced surgical technique which can also represent a unique living human model to investigate intrahepatic blood circulation. We report three consecutive cases in which a residual right portal branch flow was clearly detectable after first-step ALPPS, and try to further investigate this unexpected finding with intraoperative clamping tests., Methodology: Every patient was evaluated with CT scan 7 days after first-step ALPPS and Intraoperative Doppler Ultrasonography (IOUS) at both steps of the procedure., Results: In every patient, CT scan and second-step IOUS demonstrated a clear hepatopetal flow distally to the divided right portal branch. The flow was present after right biliary duct clamping and stopped after right total hilar clamping as well as after right hepatic artery occlusion., Conclusions: Neither cross-portal circulation between the two hemilivers nor trans-sinusoidal backflow from the hepatic veins can explain these findings, which are rather consistent with a refilling of the occluded portal branch through the opening of intrahepatic arterioportal shunts (APS). APS could represent the simplest homeostatic mechanism that regulate intrahepatic blood flow.

Background: The application of robotic-assisted surgery offers EndoWrist instruments and 3-D visualization of the operative field, which are improvements over traditional laparoscopy. The results of the few studies published so far have shown that living donor nephrectomy using the robot-assisted technique is safe, feasible, and offers advantages to patients., Materials and Methods: Since November 2009, 16 patients have undergone robotic-assisted living donor nephrectomy at our Institute. Patients were divided into two groups according to the surgical technique adopted for the procedure: Group A, hand-assisted robotic nephrectomy (eight patients); Group B, totally robotic nephrectomy (eight patients)., Results: Intra-operative bleeding was similar in the two groups (90 vs 100 mL for Group A and B, respectively). Median warm ischemia time was significantly shorter in Group A (2.3 vs 5.1 min for Group A and B, respectively, P-value = 0.05). Switching to the open procedure was never required. Median operative time was not significantly longer in Group A than Group B (275 min vs 250 min, respectively)., Conclusion: Robotic assisted living kidney recovery is a safe and effective procedure. Considering the overall technical, clinical, and feasibility aspects of living kidney donation, we believe that the robotic assisted technique is the method of choice for surgeon's comfort and donors' safety., (Copyright © 2014 John Wiley & Sons, Ltd.)

Introduction: Worldwide, organ shortage is a major limiting factor to transplantations. One possible way to face graft scarcity is splitting full livers into hemilivers; this procedure would allow transplantation in 2 adult recipients with the use of a single organ from a deceased donor., Objective: The goal of this study was to describe an adult-to-adult split liver operative protocol and share it between centers interested in exploring this procedure., Materials and Methods: A literature review was first conducted to elaborate on the present protocol; second, selection criteria for suitable deceased donors were identified. The technical aspects of performing the procurement were also analyzed; finally, the recipient selection criteria and the transplantation criteria were determined., Results: The donor characteristics should be consistent with the following: age≤55 years; weight≥70 kg; body mass index<28 kg/m2; intensive care unit stay<7 days; sodium level<160 mEq/L if the intensive care unit stay is >2 days; maximum transaminase value 3 times normal; hemodynamic stability; negative for hepatitis B surface antigen, hepatitis C virus, and human immunodeficiency virus; macrosteatosis<20%; macroscopic adequacy; and absence of anatomic anomalies requiring complex reconstruction. The procurement hospital should provide the preoperative computed tomography scan, liver dissector, and the intraoperative ultrasound. Indication for in situ or ex situ splitting depends on the hepatic vein outflow anatomy. Graft-to-recipient weight ratio should be ≥1%, and the graft-to-recipient spleen size ratio should be ≥0.6. United Network for Organ Sharing status 1 and 2A recipients are excluded, as are patients with transjugular intrahepatic portosystemic shunts. Hemiliver transplants are performed as in living-donor liver transplantation, and portal hyperflow is corrected by splenic artery ligation, splenectomy, and portal infusion of vasoactive drugs., Conclusions: The present protocol was proposed to test the validity of the full-left full-right split liver procedure. A retrospective analysis found that 130 transplantations were suitable for this procedure according to the present protocol in the period January 1, 2008, through December 31, 2011 (65 donors). We believe that these numbers could be greatly increased once this procedure is proven feasible and safe within the proposed criteria., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Postoperative pancreatic fistula (POPF) is a common complication of pancreatic resection. Aim of this study is to identify variables related to the development of POPF, analyze their clinical significance and discuss our current approach to the pancreatico-jejunal anastomosis. A series of 129 patients undergoing pancreatico-duodenectomy (PD) have been analyzed. Patients were divided in two groups: group F, 26 patients who have developed POPF; group NF, 103 patients who have not developed POPF. Demographic, clinical and intraoperative data were compared. Seventy-six patients had an end-to-side (ES) pancreatico-jejuno anastomosis, 53 an end-to-end (EE) anastomosis. Fifteen patients developed grade A fistulas, seven grade B, and four grade C; two patients with grade C fistula died from septic shock. Preoperative bile duct lithiasis, diameter of the pancreatic duct and consistency of the pancreatic stump were significantly different between F and NF groups at multivariate analysis. POPF has been related to clinical and biological parameters: preoperative bile duct lithiasis and challenging pancreatico-jejunal anastomosis (with small pancreatic duct and friable pancreatic stump) are the most prominent according to our experience. As the incidence of POPF seems to be related to technically demanding surgery, we presently reserve the EE anastomosis to the cases in which a friable gland or a very small duct will make a direct anastomosis on the pancreatic duct unreliable. In case of grade C fistulas a total spleen-preserving pancreatectomy should be considered an adequate treatment to prevent the onset of a multi-organ failure or a septic shock if no other treatment seems suitable.

Background & Aims: The current organ allocation system for liver transplantation (LT) creates an imbalance between patients with and without hepatocellular carcinoma (HCC). We describe a model designed to re-establish allocation equity among patient groups using transplant benefit as the common endpoint., Methods: We enrolled consecutive adult patients entering the waiting list (WL group, n=2697) and undergoing LT (LT group, n=1702) during the period 2004-2009 in the North Italy Transplant program area. Independent multivariable regressions (WL and LT models) were created for patients without HCC and for those with stage T2 HCC. Monte Carlo simulation was used to create distributions of transplant benefit, and covariates such as Model for End-stage Liver Disease (MELD) and alpha-fetoprotein (AFP) were combined in regression equations. These equations were then calibrated to create an "MELD equivalent" which matches HCC patients to non-HCC patients having the same numerical MELD score., Results: Median 5 year transplant benefit was 15.12 months (8.75-25.35) for the non-HCC patients, and 28.18 months (15.11-36.38) for the T2-HCC patients (p<0.001). Independent predictors of transplant benefit were MELD score (estimate=0.89, p<0.001) among non-HCC patients, and MELD (estimate=1.14, p<0.001) and logAFP (estimate=-0.46, p<0.001) among HCC patients. The equation "HCC-MELD"=1.27∗MELD - 0.51∗logAFP+4.59 calculates a numerical score for HCC patients, whereby their transplant benefit is equal to that of non-HCC patients with the same numerical value for MELD., Conclusions: We describe a method for calibrating HCC and non-HCC patients according to survival benefit, and propose that this method has the potential, if externally validated, to restore equity to the organ allocation system., (Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Objective: To analyze in a multicenter study the potential benefit of a new prospective policy development to increase split-liver procedures for 2 adult recipients., Background: Split-liver transplantation is an important means of overcoming organ shortages. Division of the donor liver for 1 adult and 1 pediatric recipient has reduced the mortality of children waiting for liver transplantation but the benefits or disadvantages to survival when the liver is divided for 2 adults (adult-to-adult split-liver transplant, AASLT) compared with recipients of a whole graft have not been fully investigated., Methods: We developed a computerized algorithm in selected donors for 2 adult recipients and applied it prospectively over a 12-year period among 7 collaborative centers. Patient and graft outcomes of this cohort receiving AASLT either as full right grafts or full left grafts were analyzed and retrospectively compared with a matched cohort of adults who received a conventional whole-liver transplant (WLT). Univariate and multivariate analysis was done for selected clinical variables in the AASLT group to assess the impact on the patient outcome., Results: Sixty-four patients who received the AASLT had a high postoperative complication rate (64.1% grade III and IV) and a lower 5-year survival rate than recipients of a WLT (63.3% and 83.1%), Conclusions: AASLT should be considered a surgical option for selected smaller-sized adults only in experimental clinical studies in experienced centers.