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Background: The futility of liver transplantation in elderly recipients remains under debate in the HCV eradication era., Methods: The aim was to assess the effect of older age on outcome after liver transplantation. We used the ELTR to study the relationship between recipient age and post-transplant outcome. Young and elderly recipients were compared using a PSM method., Results: A total of 10,172 cases were analysed. Recipient age >65 years was identified as an independent risk factor associated with reduced patient survival (HR:1.42 95%CI:1.23-1.65,p < 0.001). After PSM, 2124 patients were matched, and the same association was found between elderly recipients and patient survival and graft survival (p < 0.001). As hepatocellular carcinoma and alcoholic cirrhosis were independent prognostic factors for patient and graft survival a propensity score-matching was performed for each. Patient and graft survival were significantly worse (p < 0.05) in the alcoholic cirrhosis elderly group. However, patient and graft survival in the hepatocellular carcinoma cohort were similar (p > 0.05) between groups., Conclusion: Liver transplantation is an acceptable and safe curative option for elderly transplant candidates, with worse long-term outcomes compare to young candidates. The underlying liver disease for liver transplantation has a significant impact on the selection of elderly patients., (Copyright © 2021 International Hepato-Pancreato-Biliary Association Inc. All rights reserved.)

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are prevalent liver conditions that underlie the development of life-threatening cirrhosis, liver failure and liver cancer. Chronic necro-inflammation is a critical factor in development of NASH, yet the cellular and molecular mechanisms of immune dysregulation in this disease are poorly understood. Here, using single-cell transcriptomic analysis, we comprehensively profiled the immune composition of the mouse liver during NASH. We identified a significant pathology-associated increase in hepatic conventional dendritic cells (cDCs) and further defined their source as NASH-induced boost in cycling of cDC progenitors in the bone marrow. Analysis of blood and liver from patients on the NAFLD/NASH spectrum showed that type 1 cDCs (cDC1) were more abundant and activated in disease. Sequencing of physically interacting cDC-T cell pairs from liver-draining lymph nodes revealed that cDCs in NASH promote inflammatory T cell reprogramming, previously associated with NASH worsening. Finally, depletion of cDC1 in XCR1 DTA mice or using anti-XCL1-blocking antibody attenuated liver pathology in NASH mouse models. Overall, our study provides a comprehensive characterization of cDC biology in NASH and identifies XCR1 + cDC1 as an important driver of liver pathology.

Objective: To detail the implementation of a dedicated liver surgery program at a university-affiliated hospital and to analyze its impact on the community, workforce, workload, complexity of cases, the short-term outcomes, and residents and young faculties progression toward technical autonomy and academic production., Background: Due to the increased burden of liver tumors worldwide, there is an increased need for liver centers to better serve the community and facilitate the education of trainees in this field., Methods: The implementation of the program is described. The 3 domains of workload, research, and teaching were compared between 2-year periods before and after the implementation of the new program. The severity of disease, complexity of procedures, and subsequent morbidity and mortality were compared., Results: Compared with the 2-year period before the implementation of the new program, the number of liver resections increased by 36% within 2 years. The number of highly complex resections, the number of liver resections performed by residents and young faculties, and the number of publications increased 5.5-, 40-, and 6-fold, respectively. This was achieved by operating on more severe patients and performing more complex procedures, at the cost of a significant increase in morbidity but not mortality. Nevertheless, operations during the second period did not emerge as an independent predictor of severe morbidity., Conclusions: A new liver surgery program can fill the gap between the demand for and supply of liver surgeries, benefiting the community and the development of the next generation of liver surgeons., Competing Interests: Disclosure: The authors declare that they have nothing to disclose., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: The main goal of these studies is to provide an experimental test of a core hypothesis based on attachment theory: Working models of mother are active in adults' minds and can bias their views of self and romantic partners., Method: In two studies, we conducted clinical interviews to identify positive and negative core traits that participants used to describe their mothers. We then implicitly primed either positive or negative traits extracted from the interviews and compared this priming condition to control conditions in which we primed either positive or negative control traits (traits that described the mother of another study participant). Following this manipulation, we assessed participants' self-appraisals (Study 1) and explanations of their romantic partner's hurtful behaviors (Study 2)., Results: Priming with one's mother's positive traits led to more positive views of self and romantic partner (compared with the effects of priming with positive control traits). In contrast, as compared to negative control traits, the priming of one's mother's negative traits led to less positive views of self and romantic partner., Conclusions: Findings support the hypothesis that working models of mother play a causal role in shaping adults' representations of self and romantic partners., (© 2019 Wiley Periodicals, Inc.)

Non-tumoral portal vein thrombosis (PVT) is present at liver transplantation in 5% to 26% of cirrhotic patients, and the prevalence of complex PVT as defined here (grade 4 Yerdel, and grade 3,4 Jamieson and Charco) has been reported in 0% to 2.2%. Adequate portal inflow is mandatory to ensure graft and patient survival after liver transplantation. With time, the proposed classifications of non-tumoral chronic PVT have evolved from being anatomy-based, to also incorporating functional parameters. However, none of the currently proposed classifications are directed towards decision-making, regarding the choice of inflow to the graft during transplantation and the outcomes thereof. The present scoping review i) addresses the limits of the currently available classifications in terms of surgical decisiveness, ii) clarifies the concept of physiological or non-physiological portal inflow reconstruction, and subsequently, iii) proposes a new classification of non-tumoral PVT in candidates for liver transplantation; to help tailor the surgical strategy to an individual patient, in order to provide portal inflow to the graft together with control of prehepatic portal hypertension whenever feasible., (Copyright © 2019. Published by Elsevier B.V.)

Background: No studies have investigated whether narrow margin is a risk factor for hepatocellular carcinoma recurrence outside transplantability criteria. The objective was to assess on an intent-to-treat (ITT) basis whether hepatectomy with narrow margin affects the outcomes in patients enrolled in the salvage liver transplantation (LT) strategy., Methods: From 2007 to 2016, patients enrolled in the salvage LT strategy were divided into 2 groups: narrow (<10 mm) vs. wide (≥10 mm) margin groups. R1 resection was defined as positive histologic margin involvement. Recurrence rate, transplantability rate of recurrence and ITT overall survival (ITT-OS) were evaluated., Results: A total of 81 patients were studied: 43 patients with narrow margin and 38 with wide margin. The recurrence rates, pattern and delay of recurrence, transplantability following recurrence, and ITT-OS were similar between the two groups. These results were maintained when comparing patients with R1 resection to those with R0 resection., Conclusion: On an ITT basis, hepatectomy with narrow margin or R1 resection did not impair the transplantability of recurrence and survival of patients enrolled in the salvage LT strategy. Narrow margin and even R1 resection following hepatectomy in the setting of salvage LT strategy should not be the basis for altering the strategy., (Copyright © 2019 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Some patients remain deemed unsuitable for resection after portal vein embolization (PVE) because of insufficient hypertrophy of the future remnant liver (FRL). Hepatic and portal vein embolization (HPVE) has been shown to induce hypertrophy of the FRL. The aim of this study was to provide a systematic review of the available literature on HPVE as preparation for major hepatectomy., Methods: The literature search was performed on online databases. Studies including patients who underwent preoperative HPVE were retrieved for evaluation., Results: Six articles including 68 patients were published between 2003 and 2017. HPVE was performed successfully in all patients with no mortality and morbidity-related procedures. The degree of hypertrophy of the FRL after HPVE ranged from 33% to 63.3%. Surgical resection after preoperative HPVE could be performed in 85.3% of patients, but 14.7% remained unsuitable for resection because of insufficient hypertrophy of the FRL or tumor progression. Posthepatectomy morbidity and mortality rates were 10.3% and 5.1%, respectively. The postoperative liver failure rate was nil., Conclusion: HPVE as a preparation for major hepatectomy appears to be feasible and safe and could increase the resectability of patients initially deemed unsuitable for resection because of absent or insufficient hypertrophy of the FRL after PVE alone., (Copyright © 2019 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

OBJECTIVE. Local ablation of hepatocellular carcinoma (HCC) before liver transplant has important advantages, such as preventing disease progression, tumor downstaging, and offering a test of time. However, it might render liver transplant more technically demanding. Thus far, its potential effect on liver transplant outcomes is still unknown, and, therefore, the current study was performed. MATERIALS AND METHODS. Patients who underwent liver transplant for HCC at a single tertiary referral center between 2008 and 2016 were included and retrospectively analyzed. Patients who underwent liver resection and local ablation before liver transplant were excluded. Patients treated with local ablation before liver transplant were compared with those not treated with local ablation, both before and after propensity score matching. In addition, the local ablation group was compared with patients who underwent primary resection before liver transplant. Posttreatment mortality and morbidity were determined, and overall and disease-free survival rates were calculated. RESULTS. In total, 182 patients were included. Twenty-six patients underwent resection but not local ablation before liver transplant. Of the remaining 156 patients, 66 (42%) underwent local ablation before liver transplant and 90 (58%) did not. Perioperative mortality and morbidity were similar in both groups before and after propensity score matching (8% and 74% in the local ablation group vs 10% and 83% in the non-local ablation group, p = 0.60 and 0.17, respectively). In addition, no significant differences in long-term outcomes were observed between the groups before and after propensity score matching. Also, no differences were observed in outcomes in the local ablation group versus the liver resection group. CONCLUSION. Local ablation before liver transplant does not have a negative effect on outcomes after liver transplant for HCC.

Background: This study assessed the prognostic value of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) in the prediction of MVI and early recurrence following resection., Method: This prospective study (ClinicalTrials.gov ID: NCT02145013) included 78 consecutive HCC patients who underwent 18F-FDG PET/CT before curative-intent resection from 2014 to 2017. Prognostic factors available before surgery for predicting MVI and early recurrence (≤2 years) were identified by univariate and multivariate analyses., Results: The 18F-FDG PET/CT result was positive in 30 (38%) patients. MVI was present in 33% (26/78) of specimens. Early recurrence occurred in 19% (14/74) of surviving patients. PET/CT positivity was the sole independent predictor of MVI (odds ratio [OR] = 3.6, 95% confidence interval [CI] = 1.1-11.2; p = 0.03), with a specificity and sensitivity for predicting MVI of 73% and 62%, respectively. Analysis of variables available before surgery showed that PET/CT positivity (hazard ratio [HR] = 5.8, 95% CI = 1.6-20.4; p = 0.006) and the male sex (HR = 6.6; 95% CI = 1.8-24.2; p = 0.005) were independent predictors of early recurrence., Conclusion: 18F-FDG PET/CT predicts MVI and early recurrence after surgery for HCC and could be used to select patients for neoadjuvant treatment., (Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Resection offers the only chance of long-term survival or cure for perihilar cancer, provided R0 resection is achieved with margin-negative status of the remnant liver, bile duct, proximal hepatic artery, and portal vein. End-to-end anastomosis of the portal trunk to the left portal branch is the conventional portal reconstruction in cases of right extended hepatectomy requiring resection of the portal vein bifurcation. This mandatory reconstruction may be challenging due to (1) vessel incongruence, (2) fragility of the left portal branch wall, and more importantly, and (3) the divergent orientation of the two vessels exposing to vascular twisting/kinking. We report here the first two cases of porto-Rex shunt, between the portal vein trunk and the left portal vein in the umbilical fissure during right extended hepatectomy for advanced extrahepatic biliary cancer: one following failed conventional portal reconstruction and one to achieve macroscopically complete resection.

Background: The laparoscopic approach might increase the number of cirrhotic patients with hepatocellular carcinoma (HCC) indicated for liver resection, otherwise contraindicated due to portal hypertension. The goal of this study was to confirm the safety of laparoscopic liver resection (LLR) in patients with portal hypertension., Methods: This prospective, single-center, open study (ClinicalTrials.gov ID: NCT02145013) included all consecutive cirrhotic patients who underwent LLR for HCC from 2014 to 2017. Short-term outcomes were compared between patients with and without clinically significant portal hypertension (CSPH, defined by hepatic venous pressure gradient ≥ 10 mmHg)., Results: The study population included 45 patients, comprising 27 patients (60%) in the no CSPH group and 18 patients (40%) in the CSPH group. All planned procedures could be performed. The two groups did not differ in the extent of resection, transfusion, duration of clamping, and need for conversion. Overall, the 90-day mortality and severe morbidity rates were nil. Moderate morbidity was significantly higher in the CSPH group (39 vs. 4%, p = 0.01); however, the two groups did not differ in the rate of unresolved liver decompensation. Intensive care unit and hospital stays were significantly longer in the CSPH group. At 2 years, overall survival was 77% in the no CSPH group and 100% in the CSPH group (p = 0.17), and recurrence-free survival was 55% in the no CSPH group and 79% in the CSPH group (p = 0.10)., Conclusion: LLR is safe in BCLC 0-A patients with CSPH, with no mortality and good short-term outcomes. Re-evaluation of the BCLC guidelines is needed.

Background: Elderly recipients are frequently discussed by the scientific community but objective indication for this parameter has been provided. The aim of this study was to synthesize the available evidence on liver transplantation for elderly patients to assess graft and patient survival., Methods: A literature search of the Medline, EMBASE, and Scopus databases was carried out from January 2000 to August 2018. Clinical studies comparing the outcomes of liver transplantation in adult younger (<65 years) and elderly (>65 years) populations were analyzed. The primary outcomes were patient mortality and graft loss rates. This review was registered (Number CRD42017058261) as required in the international prospective register for systematic review protocols (PROSPERO)., Results: Twenty-two studies were included involving a total of 242,487 patients (elderly: 23,660 and young: 218,827) were included in this study. In the meta-analysis, the elderly group had patient mortality (hazard ratio [HR]: 1.26; 95% confidence interval [CI]: 0.97-1.63; P = 0.09; I2 = 48%) and graft (HR: 1.09; 95% CI: 0.81-1.47; P = 0.59; I2 = 12%) loss rates comparable to those in the young group., Conclusions: Elderly patients have similar long-term survival and graft loss rates as young patients. Liver transplantation is an acceptable and safe curative option for elderly transplant candidates., (Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.)

Backgrounds/aims: Preservation of the native inferior vena cava using a large graft during adult whole liver transplantation is associated with a potential risk of hepatic venous outflow compression/obstruction, which may adversely affect both graft and short-term patient outcomes. Intraoperative placement of materials to restore adequate hepatic venous outflow can overcome this complication., Methods: Data of patients who underwent liver transplantation between 2011 and 2016 were retrospectively reviewed. All cases of hepatic venous outflow obstruction due to large graft size managed via intraoperative intervention were analyzed. The literature was searched for studies reporting adult cases of hepatic venous outflow obstruction following whole liver transplantation managed extrahepatically., Results: Three patients diagnosed with intraoperative hepatic venous outflow obstruction due to large graft size were managed via retro-hepatic placement of breast implants (2 cases) or abdominal pads (1 case). It was successfully carried out in all cases. Four studies including 15 patients were identified in the literature search. Different types of materials such as inflatable materials (Foley catheter, Blakemore balloon), surgical gloves or breast implants, were used., Conclusions: Placement of inflatable materials leads to gradual deflation in the postoperative period, which might obviate the need for reoperation. Breast implants could be left in place indefinitely due to their bio-inert nature.

Neuroendocrine tumors are slow-growing tumors and associated with prolonged overall survival even in the presence of untreated liver metastases. The presence of liver metastases may be responsible for severe symptoms with impairment of quality of life. Liver resection has been proposed to achieve better symptom control and/or improve overall survival, but this concerns less than 20% of patients with liver metastases. In addition, the chance to be really cured after liver resection is around 40%, which prompts consideration of liver transplantation as the only potential curative treatment. Time has come to move beyond the traditional debate around the best candidates and prognostic factors for liver transplantation. This review gives the opportunity to discuss new insights: (1) outcome of liver transplantation for neuroendocrine liver metastases as compared with hepatocellular carcinoma, (2) outcome of salvage liver transplantation as a secondary procedure after surgical resection of neuroendocrine liver metastases, (3) outcome of palliative liver transplantation for neuroendocrine liver metastases, and (4) the chance to be cured after liver transplantation for neuroendocrine liver metastases., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: Postoperative complications (POCs) after the resection of locally advanced colorectal cancer (CRC) may influence adjuvant treatment timing, outcomes, and survival. This study aimed to evaluate the impact of POCs on long-term outcomes in patients surgically treated for T4 CRC., Methods: All consecutive patients who underwent the resection of T4 CRC at a single centre from 2004 to 2013 were retrospectively analysed from a prospectively maintained database. POCs were assessed using the Clavien-Dindo classification. Patients who developed POCs were compared with those who did not in terms of recurrence-free survival (RFS) and overall survival (OS)., Results: The study population comprised 106 patients, including 79 (74.5%) with synchronous distant metastases. Overall, 46 patients (43%) developed at least one POC during the hospital stay, and of those patients, 9 (20%) had severe complications (Clavien-Dindo ≥ grade III). POCs were not associated with OS (65% with POCs vs. 69% without POCs; p = 0.72) or RFS (58% with POCs vs. 70% without POCs; p = 0.37). Similarly, POCs did not affect OS or RFS in patients who had synchronous metastases at diagnosis compared with those who did not., Conclusions: POCs do not affect the oncological course of patients subjected to the resection of T4 CRC, even in cases of synchronous metastases.

Background: Elective liver resection (LR) in Jehovah's Witness (JW) patients, for whom transfusion is not an option, involves complex ethical and medical issues and surgical difficulties., Methods: Consecutive data from a LR program for liver tumors in JWs performed between 2014 and 2017 were retrospectively reviewed. A systematic review of the literature with a pooled analysis was performed., Results: Ten patients were included (median age = 61 years). None needed preoperative erythropoietin. Tumor biopsy was not performed. Major hepatectomy was performed in 4 patients. The median estimated blood loss was 200 mL. A cell-saver was installed in 2 patients, none received saved blood. The median hemoglobin values before and at the end of surgery were 13.4 g/dL and 12.6 g/dL, respectively (p = 0.04). Nine complications occurred in 4 patients, but no postoperative hemorrhage occurred. In-hospital mortality was nil. Nine studies including 35 patients were identified in the literature; there was reported no mortality and low morbidity. None of the patients were transfused., Conclusions: By using a variety of blood conservation techniques, the risk/benefit ratio of elective liver resection for liver was maintained in selected adult JW patients. JW faith should not constitute an absolute exclusion from hepatectomy., (Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Emergency digestive surgery is being increasingly performed in elderly patients. The aim of the present study was to identify the predictors of mortality and morbidity following emergency digestive surgery in patients aged 80 years and older., Methods: A single-center retrospective review was performed of consecutive patients aged ≥65 years operated for a digestive surgical emergency between January 2011 and December 2013. Two groups were compared: group A (aged 65-79 years) and group B (aged ≥80 years)., Results: The study population included 185 patients: 76 patients in group A and 109 in group B. The mean age was 79.9 years (65-104 years). The overall 90-day mortality rate was 23.2 and 31.9% at 1 year, which was similar between groups. The overall morbidity was 28.6%. No differences were noted between the two groups in overall, minor (Dindo I-II) or major (Dindo III-IV) morbidity rates. Multivariate analysis identified pulmonary disease (odds ratio, OR = 6.43, p = 0.02), bowel ischemia (OR = 11.41, p = 0.01), postoperative ICU stay (OR = 7.37, p < 0.0001) and the occurrence of postoperative complications (OR = 2.66, p = 0.03) as predictors of 90-day mortality. Predictors of in-hospital morbidity were preoperative hemoglobin <12 g/dL (OR = 2.49, p = 0.02) and postoperative intensive care unit (ICU) stay (OR = 6.69, p < 0.0001). An age ≥80 year was not associated with mortality or morbidity in this study., Conclusions: The decision to perform abdominal surgery in the emergency setting should be based on physiological status, which accounts for a patient's comorbidities and health status, rather than on chronological age per se.

The management of large spontaneous portosystemic shunt (SPSS) during liver transplantation (LT) is a matter of debate. The aim of this study is to compare the short-term and longterm outcomes of SPSS ligation versus nonligation during LT, when both options are available. From 2011 to 2017, 66 patients with SPSS underwent LT: 56 without and 10 with portal vein thrombosis (PVT), all of whom underwent successful thrombectomy and could have portoportal reconstruction. The SPSS were either splenorenal (n = 40; 60.6%), left gastric (n = 16; 24.2%), or mesenterico-iliac (n = 10; 15.1%). Following portoportal anastomosis, the SPSS was ligated in 36 (54.4%) patients and left in place in 30 (45.5%) patients, based on the effect of the SPSS clamping/unclamping test on portal vein flow during the anhepatic phase. Intraoperatively, satisfactory portal flow was obtained in both groups. Primary nonfunction (PNF) and primary dysfunction (PDF) rates did not differ significantly between the 2 groups. Nonligation of SPSS was significantly associated with a higher rate of postoperative encephalopathy (P < 0.001) and major postoperative morbidity (P = 0.02). PVT occurred in 0 and 3 patients in the ligated and nonligated shunt group, respectively (P = 0.08). A composite end point, which included the relevant complications in the setting of SPSS in LT (ie, PNF and PDF, PVT, and encephalopathy) was present in 16 (44.4%) and 22 (73.3%) patients of the ligated and nonligated shunt group, respectively (P = 0.02). Patient (P = 0.05) and graft (P = 0.02) survival rates were better in the ligated shunt group. In conclusion, the present study supports routine ligation of large SPSS during LT whenever feasible. Liver Transplantation 24 505-515 2018 AASLD., (© 2018 by the American Association for the Study of Liver Diseases.)

Background: Western guidelines recommend resection for hepatocellular carcinoma (HCC) in so-called ideal cirrhotic patients with a Barcelona Clinic Liver Cancer (BCLC) stage 0-A tumour. This study compares short-term outcomes following resection between patients defined as ideal and nonideal according to the BCLC guidelines., Methods: This prospective single-centre open study (ClinicalTrials.govNCT02145013) included all cirrhotic patients with HCC referred for resection from 2014 to 2016. Mortality, morbidity, unresolved liver decompensation, and readmission were measured., Results: The study population included 65 consecutive patients: 32 (49%) ideal and 33 (51%) nonideal. Ideal and nonideal groups did not differ in mortality (3% vs. 6%; p = 0.57), morbidity (53% vs. 73%; p = 0.10), or unresolved liver decompensation (6% vs. 15%; p = 0.23) at 90 days. The readmission rate was higher in the nonideal (21%) than in the ideal group (3%; p = 0.02)., Conclusion: Straying from the current guidelines for resection in a selected subset of nonideal patients doubled the number of resections performed for treating HCC, with satisfactory short-term outcomes. These results argue for the expansion of the acknowledged BCLC guidelines., (Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Portal hypertension (PHTN) increases the risk of non-hepatic surgery in cirrhotic patients. This first systematic review analyzes the place of transjugular intrahepatic portosystemic shunt (TIPS) in preparation for non-hepatic surgery in such patients., Methods: Medline, EMBASE, and Scopus databases were searched from 1990 to 2017 to identify reports on outcomes of non-hepatic surgery in cirrhotic patients with PHTN prepared by TIPS. Feasibility of TIPS and the planned surgery, and the short- and long-term outcomes of the latter were assessed., Results: Nineteen studies (64 patients) were selected. TIPS was indicated for past history of variceal bleeding and/or ascites in 22 (34%) and 33 (52%) patients, respectively. The planned surgery was gastrointestinal tract cancer in 38 (59%) patients, benign digestive or pelvic surgery in 21 (33%) patients and others in 4 (6%) patients. The TIPS procedure was successful in all, with a nil mortality rate. All patients could be operated within a median delay of 30 days from TIPS (mortality rate = 8%; overall morbidity rate = 59.4%). One year overall survival was 80%., Conclusions: TIPS allows non-hepatic surgery in cirrhotic patients deemed non operable due to PHTN. Further evidence in larger cohort of patients is essential for wider applicability., (Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Single-incision robotic cholecystectomy has been developed to decrease post-operative pain and improve cosmetic results., Methods: Thirty-seven patients underwent single-site robotic cholecystectomy between 2014 and 2015. Postoperative outcomes and costs were compared to reported outcomes for laparoscopic cholecystectomy using the configuration of suprapubic trocars., Results: The median age was comparable between the two groups (46 years in the robotic group vs. 47 years in the laparoscopic group). The operative time was longer in the robotic group (132 minutes) than in the laparoscopic group (53 minutes). The average length of stay was 1 day in the robotic group and 1.7 days in the laparoscopic group. Costs were higher in the robotic group (2229.46 €) than in the laparoscopic group (1141 €). In the robotic group, the trocar-site infection rate was 13.5%., Conclusion: The robotic approach does not seem to offer additional benefit in terms of surgical outcomes., (Copyright © 2017 John Wiley & Sons, Ltd.)

The salvage liver transplantation (LT) strategy was conceived for initially resectable and transplantable hepatocellular carcinoma (HCC) to obviate upfront transplantation, with salvage LT in the case of recurrence. The longterm outcomes of a second resection for recurrent HCC have improved. The aim of this study was to perform an intention-to-treat analysis of overall survival (OS) comparing these 2 strategies for initially resectable and transplantable recurrent HCC. From 1994 to 2011, 391 patients with HCC who underwent salvage LT (n = 77) or a second resection (n = 314) were analyzed. Of 77 patients in the salvage LT group, 21 presented with resectable and transplantable recurrent HCC and 18 underwent transplantation. Of 314 patients in the second resection group, 81 presented with resectable and transplantable recurrent HCC and 81 underwent a second resection. The 5-year intention-to-treat OS rates, calculated from the time of primary hepatectomy, were comparable between the 2 strategies (72% for salvage transplantation versus 77% for second resection; P = 0.57). In patients who completed the salvage LT or second resection procedure, the 5-year OS rates, calculated from the time of the second surgery, were comparable between the 2 strategies (71% versus 71%; P = 0.99). The 5-year disease-free survival (DFS) rates were 72% following transplantation and 18% following the second resection (P < 0.001). Similar results were observed after propensity score matching. In conclusion, although the 5-year OS rates were similar in the salvage LT and second resection groups, the salvage LT strategy still achieves better DFS. Second resection for recurrent HCC might be considered to be the best alternative option to LT in the current organ shortage. Liver Transplantation 23 1553-1563 2017 AASLD., (© 2017 by the American Association for the Study of Liver Diseases.)

In patients with malignancy who receive aflibercept based chemotherapy, gastrointestinal perforation is among the reported adverse events with a prevalence of 1.9%. This complication may lead to mortality up to 10.8%. We here report a case of small bowel perforation that occurred fifteen days after the first cycle of aflibercept in a 58-year old female who had metachronous colorectal liver metastases. Emergency laparotomy was performed and revealed a small bowel perforation without any anastomotic dehiscence. Surgery was followed by uneventful outcome. The use of aflibercept in patients with malignancy may be associated with very early gastrointestinal perforation and this should be known by oncologist and surgeons.

Background & Aims: The Barcelona Clinic Liver Cancer (BCLC) guidelines recommend resection for very early and early single hepatocellular carcinoma (HCC) patients. It is not known whether a delay in resection from the time of diagnosis (the time to surgery [TTS], i.e. the elapsed time from diagnosis to surgery) affects outcomes. We aim to evaluate the impact of TTS on recurrence and survival outcomes in patients with HCC., Methods: All patients resected for BCLC stage 0-A single HCC from 2006 to 2016 were studied to evaluate the impact of TTS on recurrence rate, recurrence-free survival (RFS), transplantability following recurrence, and intention-to-treat overall survival (ITT-OS). Propensity score matching (PSM) was further performed to ensure comparability., Results: The study population included 100 patients. Surgery was performed between 0.6 and 77 months after diagnosis (median TTS: three months; interquartile range: 1.8-4.6 months). There was no post-operative mortality. Compared to those with TTS <3 months, patients with TTS ≥3 months (70% of these patients had TTS 3-6 months) had a higher post-operative morbidity (36% vs. 16%, p = 0.02), a similar tumor recurrence rate (32% vs. 32%, p = 1.00), RFS (37% vs. 48%, p = 0.42), transplantability following tumor recurrence (63% vs. 50%, p = 0.48), and five-year ITT-OS (82% vs. 80%, p = 0.20). Similar results were observed after PSM., Conclusion: Patients with BCLC stage 0-A single HCC can undergo surgery with TTS ≥3 months without impaired oncologic outcomes. An increase in the TTS within a safe range could allow time for proper evaluation before surgery, and ethical testing of new neoadjuvant treatments, aiming to reduce the high rate of tumor recurrence despite curative resection., Lay Summary: A delay of ≥3 months in time to resection after diagnosis in HCC patients meeting the European Association for the Study of Liver Disease/American Association for the Study of Liver Disease criteria for resection does not affect oncological and long-term outcomes compared to those with a delay to surgery of <3 months., (Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Backgrounds/aims: Postoperative diaphragmatic hernia, following liver resection, is a rare complication., Methods: Data of patients who underwent major hepatectomy for liver tumors, between 2011 and 2015 were retrospectively reviewed. The literature was searched for studies reporting the occurrence of diaphragmatic hernia following liver resection., Results: Diaphragmatic hernia developed in 2.3% of patients (3/131) with a median delay of 14 months (4-31 months). One patient underwent emergency laparotomy for bowel obstruction and two patients underwent elective diaphragmatic hernia repair. At last follow-up, no recurrences were observed. Fourteen studies including 28 patients were identified in the literature search (donor hepatectomy, n=11: hepatectomy for liver tumors, n=17). Diaphragmatic hernia was repaired emergently in 42.9% of cases and digestive resection was necessary in 28.5% of the cases. One patient died 3 months after hepatectomy, secondary to sepsis, from a segment of small bowel that perforated into the diaphragmatic hernia., Conclusions: Although rare, diaphragmatic hernia should be considered as an important complication, especially in living donor liver transplant patients. Diaphragmatic hernia should be repaired surgically, even for asymptomatic patients.

Introduction: Anti-N-methyl-D-aspartate (NMDA) encephalitis is a disorder characterized by acute neuro-psychiatric symptoms, appearing mostly after a recent febrile disease, with a gradual progressive course, associated with laboratory or radiologic evidence of active inflammation. Many of the patients will present with a continuous neuro-cognitive disorder which could lead to major morbidity and even mortality. It was recently reported that this disorder can present at childhood as a primary disease or as a secondary complication of herpes simplex infection. Early diagnosis and treatment have significantly improved the patients' prognosis and prevented chronic complications. We will present six pediatric patients at ages 1-14 years, followed from 2011-2014 in Schneider Children's Medical Center and Assaf Harofeh Medical Center due to acute encephalitis, with a clinical course under suspicion for anti-NMDA encephalitis. The article will review the clinical and diagnostic dilemmas and suggested guidelines. Pediatricians should be aware of this new emerging syndrome.

Background: The impact of postoperative complications (POCs) on long-term outcomes following hepatocellular carcinoma (HCC) resection remains to be ascertained., Methods: All consecutive HCC resected at a single center were analyzed. Patients with POCs, classified according to Clavien classification, were compared to those without in terms of demographics, pathology, management, overall survival (OS), and disease-free survival (DFS). Independent prognostic factors of POCs were identified using multivariable regression models., Results: Among 341 patients, overall POCs rate was 34% (n = 116) and grade III-IV POCs rate was 14.4% (n = 49). POCs were an independent negative factor for OS [hazard ratio (HR) 1.40, 95% confidence interval (CI) 1.12-2.26, p = 0.009] with BCLC stage, the need for combined procedure, intraoperative transfusion, and the METAVIR score of the underlying parenchyma. Similarly, occurrence of POCs was associated independently with DFS (HR 1.59, 95% CI 1.18-2.15, p = 0.002), together with the presence of portal hypertension, BCLC stage, the need for combined procedure, intraoperative transfusion, and the presence of satellite nodules. After stratification, the negative impact of morbidity on OS and DFS reached statistical significance in the BCLC stage A subset only (p = 0.026, and p < 0.001, respectively). Open resection, intraoperative transfusion, and the existence of underlying liver injury were independent predictors of POCs., Conclusions: POCs should be considered as a long-term prognostic factor. Careful patient selection requiring underlying liver assessment and appropriate strategy, such as mini-invasive surgery and restricted transfusion policy, might be promoted to prevent POCs.

Background: The impact of intraoperative blood transfusion (IBT) on outcomes following intrahepatic cholangiocarcinoma (IHCC) resection remains to be ascertained., Methods: All consecutive IHCC resected were analyzed. A first cohort (n = 569) was used for investigating short-term outcomes (morbidity and mortality). A second cohort (n = 522) excluding patients dead within 90 days of surgery was analyzed for exploring overall survival (OS) and disease free survival (DFS). Patients who received IBT were compared to those who did not, after using a propensity score matching (PSM) method., Results: Among 569 patients, 90-day morbidity and mortality rates were 47% (n = 269) and 8% (n = 47). After PSM, 208 patients were matched. There was an association between IBT and increased overall morbidity and severe morbidity (p = 0.010). However, IBT did not impact 90-day mortality rate (p > 0.999). Regarding long-term outcomes analysis in the second cohort (n = 522), 5-year OS and DFS rates were 39% and 25%. Using PSM, 196 patients were matched and no association between IBT and OS or DFS was found (p = 0.333 and p = 0.491)., Conclusions: IBT is associated with an increased risk of morbidity but does not impact on long-term outcomes. Need for IBT should be considered as a surrogate of advanced disease requiring complex resection. Still, restricted transfusion policy should remain advocated for IHCC resection., (Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Aim: There are few reports on the tolerability and efficacy of perampanel, a new antiepileptic drug with a novel mechanism of action, in children and adolescents. We aimed to describe our experience with perampanel add-on and mono-therapy in children with refractory epilepsy., Method: Computerized medical records of children treated with perampanel in the paediatric neurology clinic from December 2012 to October 2015 were reviewed., Results: Twenty-four children treated with perampanel (15 females, 9 males) aged 1 year 6 months to 17 years (mean 10y, standard deviation [SD] 4y 5mo) were identified. Adverse events were more common in children aged 12 years or older (89%) compared to younger children (53%), and were mainly behavioural. Ten (42%) children had 50 per cent or higher seizure reduction, two (8%) children had 33 per cent seizure reduction, and seizures were less severe in one (4%) child. Perampanel was discontinued in 13 (54%) children mostly due to adverse events. The mean duration of follow-up in the remaining 11 children was 8.1 months (SD 5.2) (range 1.3-17mo)., Interpretation: Perampanel is associated with a relatively high rate of behavioural adverse events mostly in adolescents with refractory epilepsy., (© 2016 Mac Keith Press.)

Background: After comparing with open approach, left lateral sectionectomy (LLS) has become standard in terms of short-term outcomes without jeopardizing long-term survival when performed for malignancy. The aim of this study was to compare the short-term and economic outcomes of laparoscopic (L-LLS) and robotic (R-LLS) LLS., Methods: All consecutive patients who underwent L-LLS or R-LLS from 1997 to 2014 were analyzed. Short-term and economic outcomes were compared between the two groups using a propensity score matching (PSM)., Results: Ninety-six consecutive cases of LLS were performed using the laparoscopic (80 cases; 83 %) or robotic (16 cases; 17 %) approach. The two groups were similar for operative and surgical outcomes. Operation time was similar in the R-LLS compared to the L-LLS group (190 vs. 162 min; p = 0.10). Perioperative costs were higher (1457 € vs. 576 €; p < 0.0001) in the R-LLS group than in the L-LLS group; however, postoperative costs were similar between the two groups (4065 € in the R-LLS group vs. 5459 € in the L-LLS group; p = 0.30). Total costs were similar between the two groups (5522 € in the R-LLS group vs. 6035€ in the L-LLS group; p = 0.70). The PSM included 14 patients for each group. Surgical and economic outcomes remained similar after PSM, except for total operating time which was significantly longer in the R-LLS group than in the L-LLS group., Conclusions: Even if feasible and safe, the robotic approach does not seem so far to offer additional benefit in terms of intra- and postoperative outcomes over the laparoscopic approach in patients requiring LLS. Total costs associated with the R-LLS group are not greater than that associated with the L-LLS group, which is the standard of care so far.

Background: The management of pancreatic trauma is complex. The aim of this study was to report our experience in the management of pancreatic trauma., Methods: All patients hospitalized between 2005 and 2013 for pancreatic trauma were included. Traumatic injuries of the pancreas were classified according to the American Association for Surgery of Trauma (AAST) in five grades. Mortality and morbidity were analyzed., Results: A total of 30 patients were analyzed (mean age: 38±17 years). Nineteen (63%) patients had a blunt trauma and 12 (40%) had pancreatic injury ≥ grade 3. Fifteen patients underwent exploratory laparotomy and the other 15 patients had nonoperative management (NOM). Four (13%) patients had a partial pancreatectomy [distal pancreatectomy (n=3) and pancreaticoduodenectomy (n=1)]. Overall, in hospital mortality was 20% (n=6). Postoperative mortality was 27% (n=4/15). Mortality of NOM group was 13% (n=2/15) in both cases death was due to severe head injury. Among the patients who underwent NOM, three patients had injury ≥ grade 3, one patient had a stent placement in the pancreatic duct and two patients underwent endoscopic drainage of a pancreatic pseudocyst., Conclusions: Operative management of pancreatic trauma leads to a higher mortality. This must not be necessarily related to the pancreas injury alone but also to the associated injuries including liver, spleen and vascular trauma which may cause impaired outcome more than pancreas injury., Competing Interests: The authors have no conflicts of interest to declare.

Context: The management of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) is challenging, especially if it is not treatable by surgery or embolization., Objectives: The present study aims to compare the survival rates of liver transplanted patients receiving sorafenib or best supportive care (BSC) for HCC recurrence not amenable to curative intent treatments., Design: This is a retrospective comparative study on a prospectively maintained database., Participants: Liver transplanted patients with untreatable HCC recurrence receiving BSC (n = 18) until 2007 or sorafenib (n = 15) thereafter were compared., Results: No group difference was observed for demographic characteristics at the time of transplantation and at the time of HCC recurrence. On the explant pathology of the native liver, 81.2% patients were classified within the Milan criteria, and 53.1% presented with microvascular invasion. Hepatocellular carcinoma recurrence was diagnosed 17.8 months (standard deviation: 14.5) after LT, with 17 (53.1%) patients presenting with early recurrence (≤12 months). The 1-year survival from untreatable progression of HCC recurrence was 23.9% for the BSC and 60% for the sorafenib group ( P = .002). The type of treatment (sorafenib vs BSC) was the sole independent predictor of survival (hazard ratio: 2.98; 95% confidence interval: 1.09-8.1; P = .033). In the sorafenib group, 8 (53.3%) patients required dose reduction, and 2 (13.3%) patients discontinued the treatment due to intolerable side effects., Conclusion: Sorafenib improves survival and is superior to the BSC in cases of untreatable posttransplant hepatocellular carcinoma recurrence.

Background: The specific definition of central hepatectomy (CH) (i.e., resection of segments 4-5-8 ± 1) is not uniformly used, resulting in conflicting comparisons with the more commonly performed extended hepatectomy (EH). The study aimed to compare, using propensity score matching (PSM) analysis, the incidence of postoperative complications between CH and EH for centrally located liver tumors (CLLT)., Methods: All consecutive CH and EH procedures for CLLT performed from 1980 to 2011 were retrospectively reviewed. Independent predictors of postoperative complications were identified. CH was compared to EH after PSM., Results: The study population consisted of 373 patients, 44 (11.8 %) of whom underwent CH and 329 (88.2 %) of whom underwent EH. Before PSM, the overall 90-day mortality was 7.2 % (27 patients) without a group difference (2 (4.5 %) for CH vs. 25 (7.6 %) for EH, p = 0.756). The CH and EH groups had similar postoperative morbidity rates (43.2 vs. 55.3 %; p = 0.108). Blood transfusion was the only independent predictor of postoperative complications (Hazard Ratio: 1.73; 95 % confidence interval: 1.11-2.68; p = 0.014). After PSM, 43 CH patients were matched with 43 EH patients. No group difference was observed for the postoperative mortality, morbidity, or duration of hospital stay. A higher number of EH patients (30.2 vs. 9.3 %, p = 0.028) presented with more than one postoperative complication., Conclusions: CH and EH yield similar mortality and morbidity. For CLLT, CH may be an attractive procedure with the advantage of sparing the liver parenchyma compared with EH.

Background: Minimally invasive pancreaticoduodenectomy is considered hazardous for the majority of authors and minimally distal pancreatectomy is still a debated topic. The aim of this study was to compare robotic distal pancreatectomy (RDP) versus laparoscopic distal pancreatectomy (LDP) using meta-analysis., Method: EMBASE, Medline and PubMed were searched systematically to identify full-text articles comparing robotic and laparoscopic distal pancreatectomies. The meta-analysis was performed by using Review Manager 5.3., Results: Nine studies fulfilled the inclusion criteria and included 637 patients (246 robotic and 391 laparoscopic). RDP had a shorter hospital length of stay by 1 day (P = 0.01). On the other hand, LDP had shorter operative time by 30 min, although this was statistically nonsignificant (P = 0.12). RDP showed a significantly increased readmission rate (P = 0.04). There was no difference in the conversion rate, incidence of postoperative pancreatic fistula, International Study Group of Pancreatic Fistula grade B-C rate, major morbidity, spleen preservation rate and perioperative mortality. All surgical specimens of RDP reported R0 negative margins, whereas 7 specimens in the LDP group had affected margins., Conclusions: In terms of feasibility, safety and oncological adequacy, there is no essential difference between the two techniques so far. The 30 min longer operative time of the RDP is due to the docking and undocking of the robot. The shorter length of stay by 1 day should be judged in combination with the increased 90-day readmission rate., (Copyright © 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)