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Background: Posthepatectomy liver failure (PHLF) is the main limitation to extending liver resection but its pathophysiology is not yet fully understood. The aim of the study was to describe the metabolic adaptations that occur with PHLF., Methods: A retrospective study of 82 patients using nuclear magnetic resonance metabolomics to identify and quantify intra-hepatic metabolites was performed. The metabolite levels were compared using metabolic network analysis ADEMA between fatal PHLF (FLF) and non fatal PHLF and according to PHLF/ACLF grading., Results: Metabolomic profiles were significantly different between patients presenting FLF and non FLF or grade 3 ACLF versus < grade 3 ACLF. In the patients undergoing hepatectomy, valine, alanine and glycerophosphocholine were identified as powerful biomarkers to predict FLF (AUROC 0.806, 0.802 and 0.856 respectively). Network analysis showed an activation of aerobic glycolysis with glutaminolysis as observed in highly proliferating systems. Inversely, ACLF3 showed deprivation of glucose and lactate compared to lower ACLF grade., Conclusion: Clinical andbiological severity of ACLF and PHLF correlate with specific metabolic adaptations. Metabolomics can predict fatal liver failure after hepatectomy and underline significant differences in the metabolic patterns of ACLF and PHLF., (Copyright © 2019 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: The prognostic value of tumor multinodularity in intrahepatic cholangiocarcinoma (ICC) remains debated. We aimed to evaluate the impact of tumor multinodularity according to the presence and distribution of multiples ICC's nodules., Methods: A retrospective review of a prospectively maintained database of patients undergoing resection for ICC from January 1995 to September 2017 was performed. Prognostic factors for survival were assessed by multivariate Cox analysis. Tumoral nodules were defined according to their number (single and multiple) and localization (satellites and contralateral)., Results: Out of 120 selected patients, 64 (53%) had single and 56 (47%) had multiple lesions. Multiple lesions included tumors with satellites (n = 40; 71.5%) and tumors with contralateral lesions (n = 16; 28.5%). Patients with multiple tumors had significantly larger mean main lesion size (p = 0.02), required a higher rate of perioperative transfusion (p = 0.04), had a greater rate of lymph node involvement (p < 0.0001), vascular invasion (p = 0.04), and poor differentiation (p = 0.04) than single tumors. Patients with single tumors experienced a 5-year survival significantly longer (40%) than patients with multiple tumors (14%; p = 0.004). Patients having tumors with satellites had inferior median overall survival and 5-year survival rates (20 months, 7%) compared with patients with contralateral tumors (33.6 months, 29%) (p = 0.09). Multivariable analysis identified tumor multinodularity, morbidity, tumor size < 5 cm, poor differentiation, and lymph node involvement as independent prognostic factors for overall survival., Conclusions: Tumor multinodularity represents an independent risk factor for survival in ICCs and identifies a category of patients in need of more effective perioperative treatment.

Background: Despite an early radical reoperation, recurrence and poor survival are observed in up to 40% of patients with an incidentally discovered gallbladder carcinoma (I-GBC) after undergoing a laparoscopic cholecystectomy (LC). This study seeks to identify prognostic factors after re-I-GBC resection., Methods: A retrospective review of a prospectively maintained patient database with patients who were undergoing resection for I-GBC from January 1995 to March 2017 was performed. Prognostic factors for survival were assessed by multivariate Cox analysis., Results: There were 50 consecutive patients (median age 64 years; range 38-82) undergoing reoperation 45 ± 30 days after LC. Re-resection entailed a major hepatectomy in five patients (10%) and lymphadenectomy in all patients. Ninety-day morbidity and mortality were 22 and 2%, respectively. Lymph node (LN) involvement was present in 24 (48%) patients with a mean of 5.79 ± 14.4 LN+. Median overall survival was 40 months with 1-, 3-, 5- and 10-year survival rates of 80, 50, 41 and 36%, respectively. Independent risk factors for overall survival were T3 tumours (HR = 7.58; 95% confidence intervals (CI), 2.41-23.83.) and LN involvement (HR = 3.66; 95% CI, 1.42-9.45). Patients presenting with zero, one and two risk factors had 3-year survival rates of 85, 31 and 0%, respectively, and median overall survival of 80, 22 and 13 months, respectively (p < 0.0001)., Conclusions: After I-GBC discovery following an LC, T3 tumours and tumours with LN+ are characterised by poor prognosis. The presence and the identification of these prognostic factors help identify patients in need of alternative perioperative treatments.

Introduction: Bilobar colorectal metastases may be treated by a 2-stage surgical strategy. The risk of drop out after the first stage hepatectomy remains high and is associated with a nearly zero survival rate at 3 years. Our goal was to evaluate the factors predictive of the feasibility of the strategy and long-term survival, based on simple clinical and histologic features obtained from the first stage specimen., Patients and Methods: Patients who underwent a first stage hepatectomy with curative intent were included. Preoperative clinical parameters and histologic features of the primary neoplasm and metastases obtained at the first stage hepatectomy were analyzed and compared between patients who did or did not undergo the second stage operation. A group of comparable patients treated only by chemotherapy was used as a control group., Results: The feasibility rate of this 2-stage resection was 76% (38/50 patients). Median survival was greater in patients treated with chemotherapy alone than for those who failed the second stage. A clinicopathologic score including male sex, segment 1 metastasis, need for >3 resection(s)/radiofrequency ablation(s), vascular invasion in the primary, need for change in type of chemotherapy, and microscopic biliary invasion by the metastasis was predictive of feasibility of the second stage and disease-free survival in patients achieving the second stage., Conclusion: Combining preoperative clinical parameters with pathologic features of the primary and the metastatic lesions obtained during first stage hepatectomy predicted accurately patients who failed the second stage, and the long-term outcomes. Considering both clinical and pathologic parameters may help to define the best oncologic strategy by choosing between an exclusive chemotherapeutic or a surgical strategy., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to compare the long-term results of 2 surgical strategies for patients with bilobar colorectal liver metastases (bCRLM)., Background: Two-stage hepatectomy is the surgical strategy mostly chosen for treating extensive BCLM with the pitfall of dropout after the first stage. One-stage strategy combining limited resections and radiofrequency ablation could be proposed as an option in this population., Patients and Methods: Between 2000 and 2010, 272 patients were consecutively operated in 2 expert centers practicing 1- or 2-stage hepatectomy for bCRLM. A case-match study (1:1) was conducted using number and size of nodules, synchronous presentation, primary node status, and extrahepatic disease as matching variables to compare overall survival (OS) and disease-free survival (DFS). The analysis was performed in intention to treat, including patients who did not undergo the second stage., Results: In the case-match analysis (156 matched patients), median OS and DFS did not differ significantly between patients in 1- and 2-stage hepatectomy, respectively: 37.2 and 34.5 months (P=0.6), 9.4 and 7.5 months (P=0.25). Multivariate analysis confirmed the absence of impact of strategy on OS and DFS. Primary advanced T stage and synchronous presentation were predictors of poor OS (HR=3.67 and 1.92); CEA more than 200 ng/mL, absence of postoperative chemotherapy, and extrahepatic disease were predictive of recurrence (HR=2.77, 1.85 and 1.69, respectively)., Conclusions: This first case-match study demonstrates that on an intention-to-treat analysis 1- and 2-stage hepatectomy in patients with bCRLM achieve comparable OS and DFS, despite the high dropout of the 2-stage strategy.

Background: The mechanisms and kinetics of hepatic growth have continuously been investigated. This study concerns liver regeneration in animal and patients who underwent partial hepatectomy evaluated by the hepatic extraction fraction (HEF) calculated through radioisotopic methods., Methods: Thirty normal Wistar rats were submitted to an 85% hepatectomy, and 95 patients with primary and secondary liver tumours were included. In animal study, the liver regeneration kinetics was assessed by HEF using 99mTc-mebrofenin, the ratio liver/bodyweight and by using bromodeoxyuridine deoxyribonucleic acid incorporation. In patient study, the liver regeneration was evaluated by calculation of HEF before surgery, 5 and 30 days after hepatectomy., Results: In animal, we verified a positive correlation between HEF kinetics and liver/bodyweight ratio or hepatocyte proliferation evaluated by bromodeoxyuridine deoxyribonucleic acid staining after 85% hepatectomy. In the clinical arm, no statistical differences of the HEF before hepatectomy, 5 and 30 days after hepatectomy, were observed., Conclusions: Our results support the view that human liver regeneration commences early, is fast, non-anatomical and functionally complete 5 days after hepatectomy. The fast functional liver regeneration may have a high clinical impact particularly concerning the post-operative oncological therapeutic approaches., (© 2013 The Authors. ANZ Journal of Surgery © 2013 Royal Australasian College of Surgeons.)

Background: Liver regeneration enables repeat surgical procedures to achieve a potential cure in liver cancer patients. However, data regarding segmental regeneration and liver anatomy after liver resection are scarce. This study examined left liver regeneration after right hepatectomy and the impact of hepatic venous drainage on the regeneration of the paramedian sector (Couinaud's segment IV)., Methods: Twenty patients in whom right hepatectomy with conservation of the middle hepatic vein (MHV) on healthy liver had been performed were analysed for segmental volumes and vascular anatomy. Volumetric analysis of left liver segments and three-dimensional MHV reconstruction were conducted using pre- and postoperative computed tomography. The volumetric proportions represented by each segment within the left liver were compared and MHV anatomy was analysed to determine its potential role in the regeneration of left liver segments., Results: After right hepatectomy, the proportion represented by segment IV within the left liver decreases by 13%, whereas the proportion represented by segments II and III increases by 15%. This heterogeneous regeneration is particularly observed in patients in whom a venous branch for segment IVb is sacrificed, leading to an altered outflow similar to that observed in MHV deprivation. The risk for venous branch deprivation in IVb is correlated to the depth of the bifurcation of the MHV in liver parenchyma., Conclusions: It is crucial to conserve the MHV in its distal part if homogeneous left liver regeneration after right hepatectomy that will allow potential repeat liver resection is to be achieved., (© 2012 International Hepato-Pancreato-Biliary Association.)