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Our objective was to evaluate long-term outcome of children born after inadvertent administration of a gonadotrophin-releasing hormone agonist (GnRHa) in early pregnancy, compared to a control group of children born to matched women undergoing in-vitro fertilization and children born after spontaneous pregnancies. Six children from six pregnancies, exposed to a long-acting gonadotrophin agonist, comprised the study group and 20 children were included in the control groups. Pre-, peri- and postnatal data were collected and the children were followed and examined at a mean age of 7.8 ± 2.0 years. All children underwent physical and neurological examination, and psychological tests. In the study group, one child was born with a major congenital malformation (cleft palate), and four children subsequently demonstrated neurodevelopmental abnormalities, including epileptic disorder (n = 1), attention deficit hyperactivity disorder (n = 3), motor difficulties (n = 3) and speech difficulties (n = 1). In the control groups, one child had attention deficit hyperactivity disorder. This observation of neurodevelopmental abnormalities in four of six children in the study group justifies the need for long-term follow-up of more children previously exposed to gonadotrophin-releasing hormone agonist. [ABSTRACT FROM PUBLISHER]

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.)

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.)

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.)

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.

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: 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.)

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.)

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.

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.)

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.

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.)

Background: Acute kidney injury (AKI) following hepatectomy remains understudied in terms of diagnosis, severity, recovery and prognostic value. The aim of this study was to assess the risk factors and prognostic value of AKI on short- and long-term outcomes following hepatectomy for hepatocellular carcinoma (HCC)., Method: This is a retrospective analysis of a single-center cohort of 457 consecutive patients who underwent hepatectomy for HCC. The KDIGO criteria were used for AKI diagnosis. The incidence, risk factors, and prognostic value of AKI were investigated., Results: AKI occurred in 67 patients (15%). The mortality and major morbidity rates were significantly higher in patients with AKI (37% and 69%) than in those without (6% and 22%; p < 0.001). Renal recovery was complete in 35 (52%), partial in 25 (37%), and absent in 7 (11%) patients. Advanced age, an increased MELD score, major hepatectomy and prolonged duration of operation were identified as independent predictors of AKI. AKI was identified as the strongest independent predictor of postoperative mortality but did not impact survival., Conclusion: AKI is a common complication after hepatectomy for HCC. Although its development is associated with poor short-term outcomes, it does not appear to be predictive of impaired long-term survival., (Copyright © 2016. Published by Elsevier Ltd.)

Veno-venous bypass (VVB) using a patent para-umbilical vein during liver transplantation (LT) has not been reported previously. Here, we report the decompression of the porto-mesenteric compartment via a patent para-umbilical vein in a patient needing a VVB during LT. Pre-transplant CT-scan showed a large patent para-umbilical vein. A femoro-axillary percutaneous VVB was installed prior to abdominal opening to decompress massive collateral veins in the abdominal wall. The para-umbilical vein was stapled and its proximal end was cannulated and connected to the VVB. The severe atrophy of the native liver allowed to place the whole liver graft in the "liver fossa" while maintaining the native liver pulled toward the left side and connected to the VVB. This maneuver maintained splanchnic venous decompression during latero-lateral cavo-caval anastomosis. The "portal" cannula was clamped and removed. The native portal vein was clamped and divided. Standard portal, arterial, and biliary reconstructions were then performed. A patent para-umbilical vein, present in one third of patients with portal hypertension could be used whenever VVB is indicated during LT in this setting.

Here we report inherited dysregulation of protein phosphatase activity as a cause of intellectual disability (ID). De novo missense mutations in 2 subunits of serine/threonine (Ser/Thr) protein phosphatase 2A (PP2A) were identified in 16 individuals with mild to severe ID, long-lasting hypotonia, epileptic susceptibility, frontal bossing, mild hypertelorism, and downslanting palpebral fissures. PP2A comprises catalytic (C), scaffolding (A), and regulatory (B) subunits that determine subcellular anchoring, substrate specificity, and physiological function. Ten patients had mutations within a highly conserved acidic loop of the PPP2R5D-encoded B56δ regulatory subunit, with the same E198K mutation present in 6 individuals. Five patients had mutations in the PPP2R1A-encoded scaffolding Aα subunit, with the same R182W mutation in 3 individuals. Some Aα cases presented with large ventricles, causing macrocephaly and hydrocephalus suspicion, and all cases exhibited partial or complete corpus callosum agenesis. Functional evaluation revealed that mutant A and B subunits were stable and uncoupled from phosphatase activity. Mutant B56δ was A and C binding-deficient, while mutant Aα subunits bound B56δ well but were unable to bind C or bound a catalytically impaired C, suggesting a dominant-negative effect where mutant subunits hinder dephosphorylation of B56δ-anchored substrates. Moreover, mutant subunit overexpression resulted in hyperphosphorylation of GSK3β, a B56δ-regulated substrate. This effect was in line with clinical observations, supporting a correlation between the ID degree and biochemical disturbance.

The liver is the most frequently injured intraperitoneal organ, despite its relatively protected location. The liver consisting of a relatively fragile parenchyma contained within the Glisson capsule, which is thin and does not provide it with great protection. The management of hepatic trauma has undergone a paradigm shift over the past several decades with significant improvement in outcomes. Shifting from mandatory operation to selective nonoperative treatment, and, presently, to nonoperative treatment with selective operation. Operative management emphasizes packing, damage control, and utilization of interventional radiology, such as angiography and embolization. Because of the high morbidity and mortality, liver resection seems to have a minimal role in the management of hepatic injury in many reports, but in a specialized referral center, like our institute, surgical treatment becomes, in many cases, the only life-saving treatment. Innovations in liver transplant surgery, living liver donation, and the growth of specialized liver surgery teams have changed the way that surgeons and hepatic resection are done.

Background/aims: Ischemia/reperfusion (I/R) injury is the main cause of both primary graft dysfunction and primary non-function of liver allografts. Cannabinoids has been reported to attenuate myocardial, cerebral and hepatic I/R oxidative injury. Delta-9-tetrahydrocannabinol (THC), a cannabinoid agonist, is the active components of marijuana. In this study we examined the role of ultralow dose THC (0.002mg/kg) in the protection of livers from I/R injury. This extremely low dose of THC was previously found by us to protect the mice brain and heart from a variety of insults., Methods: C57Bl Mice were studied in in vivo model of hepatic segmental (70%) ischemia for 60min followed by reperfusion for 6 hours., Results: THC administration 2h prior to the induction of hepatic I/R was associated with significant attenuated elevations of: serum liver transaminases ALT and AST, the hepatic oxidative stress (activation of the intracellular signaling CREB pathway), the acute proinflammatory response (TNF-α, IL-1α, IL-10 and c-FOS hepatic mRNA levels, and ERK signaling pathway activation). This was followed by cell death (the cleavage of the pro-apoptotic caspase 3, DNA fragmentation and TUNEL) after 6 hours of reperfusion. Significantly less hepatic injury was detected in the THC treated I/R mice and fewer apoptotic hepatocytes cells were identified by morphological criteria compared with untreated mice., Conclusion: A single ultralow dose THC can reduce the apoptotic, oxidative and inflammatory injury induced by hepatic I/R injury. THC may serve as a potential target for therapeutic intervention in hepatic I/R injury during liver transplantation, liver resection and trauma., (© 2015 S. Karger AG, Basel.)

Expanded surgical intervention in colorectal liver metastasis (LM) and improved chemotherapy led to increasing problem of disappearing liver metastases (DLM). Treatment of those continues to evolve and poses a real challenge for HPB surgeons. This review discusses a clinical approach to DLM, emphasizing crucial steps in clinical algorithm. Particular issues such as imaging, intraoperative detection and surgical techniques are addressed. A step-by-step algorithm is suggested.

Background: Although ablation therapy has been accepted as a promising and safe technique for treatment of unrespectable hepatic tumors, investigation of its complications has been limited. A physician who performs ablation treatment of hepatic malignancies should be aware of the broad spectrum of complications. Proper management is possible only if the physician Performing ablation understands the broad spectrum of complications encountered after ablation., Objectives: TO SYSTEMATICALLY REVIEW THE COMPLICATIONS AFTER DIFFERENT ABLATION MODALITIES: Radiofrequency ablation (RFA), microwave ablation (MWA) and Nano knife for the treatment of liver tumors and analyze possible risk factors that precipitate these complications., Search Methods: WE PERFORMED ELECTRONIC SEARCHES IN THE FOLLOWING DATABASES: MEDLINE, EMBASE and COCHARNE. Current trials were identified through the Internet (from January 1, 2000 to January 1, 2014). We included only studies who specific mentioned complications after liver ablation therapy (RFA/MWA/Nano knife)., Main Results: A total of 2,588 publications were identified, after detailed examination only 32 publications were included in the review. The included studies involved 15,744 participants. According to the type of technique, 13,044 and 2,700 patients were included for RFA and MWA. Analysis showed a pooled mortality of 0.15% for RFA, and 0.23% for MWA., Conclusions: This systematic review gathers information from controlled clinical trials and observational studies which are vulnerable to different types of bias, never the less RFA and MWA can be considered safe techniques for the treatment of liver tumors.

In the latest decades an important change was registered in liver surgery, however the management of liver cirrhosis or small size hepatic remnant still remains a challenge. Currently post-hepatectomy liver failure (PLF) is the major cause of death after liver resection often associated with sepsis and ischemia-reperfusion injury (IRI). ''Small-for-size'' syndrome (SFSS) and PFL have similar mechanism presenting reduction of liver mass and portal hyper flow beyond a certain threshold. Few methods are described to prevent both syndromes, in the preoperative, perioperative and postoperative stages. Additionally to portal vein embolization (PVE), radiological examinations (mainly CT and/or MRI), and more recently 3D computed tomography are fundamental to quantify the liver volume (LV) at a preoperative stage. During surgery, in order to limit parenchymal damage and optimize regenerative capacity, some hepatoprotective measures may be employed, among them: intermittent portal clamping and hypothermic liver preservation. Regarding the treatment, since PLF is a quite complex disease, it is required a multi-disciplinary approach, where it management must be undertaken in conjunction with critical care, hepatology, microbiology and radiology services. The size of the liver cannot be considered the main variable in the development of liver dysfunction after extended hepatectomies. Additional characteristics should be taken into account, such as: the future liver remnant; the portal blood flow and pressure and the exploration of the potential effects of regeneration preconditioning are all promising strategies that could help to expand the indications and increase the safety of liver surgery.

Purpose: The unique properties of remifentanil make it ideal for pediatric use despite a lack of wide randomized clinical trials and fear of adverse events due to its high potency. We aimed to consolidate preliminary conclusions regarding the efficacy of remifentanil use in pediatric scoliosis surgery., Materials and Methods: The medical charts of children with idiopathic scoliosis who underwent primary spinal fusion between 1998 and 2007 at a large tertiary university-affiliated hospital were retrospectively reviewed and divided into two groups according to anesthetic regime (remifentanil vs. morphine). Demographic, surgery-related details and immediate postoperative course were recorded and compared., Results: All 36 remifentanil children were extubated shortly after termination of surgery, compared to 2 of the 84 patients in the morphine group. The remaining patients in the morphine group were extubated hours after surgery [5.4 hours; standard deviation (SD) 1.7 hours]. Six remifentanil children were spared routine intensive care hospitalization (vs. 2 morphine children-significant difference). Shorter surgeries [5.6 hours (SD 1.82 hours) vs. 7.14 hours (SD 2.15 hours); p=0.0004] were logged for the remifentanil group. To achieve controlled hypotension during surgery, vasodilator agents were used in the morphine group only. A comparison of early postoperative major or minor complication rates (including neurological and pulmonary complications) between the two groups yielded no significant differences., Conclusion: Remifentanil use can shorten operating time and facilitate earlier spontaneous ventilation and extubation, with less of a need for intensive care hospitalization and no increase in significant complications.