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Background: ALPPS is found to increase the resectability of primary and secondary liver malignancy at the advanced stage. The aim of the study was to verify the surgical and oncological outcome of ALPPS for intrahepatic cholangiocarcinoma (ICC)., Methods: The study cohort was based on the ALPPS registry with patients from 31 international centers between August 2009 and January 2018. Propensity score matched patients receiving chemotherapy only were selected from the SEER database as controls for the survival analysis., Results: One hundred and two patients undergoing ALPPS were recruited, 99 completed the second stage with median inter-stage duration of 11 days. The median kinetic growth rate was 23 ml/day. R0 resection was achieved in 87 (85%). Initially high rates of morbidity and mortality decreased steadily to a 29% severe complication rate and 7% 90-day morbidity in the last 2 years. Post-hepatectomy liver failure remained the main cause of 90-day mortality. Multivariate analysis revealed insufficient future liver remnant at the stage-2 operation (FLR2) to be the only risk factor for severe complications (OR 2.91, p = 0.02). The propensity score matching analysis showed a superior overall survival in the ALPPS group compared to palliative chemotherapy (median overall survival: 26.4 months vs 14 months; 1-, 2-, and 3-year survival rates: 82.4%, 70.5% and 39.6% vs 51.2%, 21.4% and 11.3%, respectively, p < 0.01). The survival benefit, however, was not confirmed in the subgroup analysis for patients with insufficient FLR2 or multifocal ICC., Conclusion: ALPPS showed high efficacy in achieving R0 resections in locally advanced ICC. To get the most oncological benefit from this aggressive surgery, ALPPS would be restricted to patients with single lesions and sufficient FLR2.

Background & Aims: In a variety of animal models, omega-3 polyunsaturated fatty acids (Ω3-FAs) conferred strong protective effects, alleviating hepatic ischemia/reperfusion injury and steatosis, as well as enhancing regeneration after major tissue loss. Given these benefits along with its safety profile, we hypothesized that perioperative administration of Ω3-FAs in patients undergoing liver surgery may ameliorate the postoperative course. The aim of this study was to investigate the perioperative use of Ω3-FAs to reduce postoperative complications after liver surgery., Methods: Between July 2013 and July 2018, we carried out a multicentric, double-blind, randomized, placebo-controlled trial designed to test whether 2 single intravenous infusions of Omegaven® (Ω3-FAs) vs. placebo may decrease morbidity. The primary endpoints were postoperative complications by severity (Clavien-Dindo classification) integrated within the comprehensive complication index (CCI)., Results: A total of 261 patients (132 in the Omegaven and 129 in the placebo groups) from 3 centers were included in the trial. Most cases (87%, n = 227) underwent open liver surgery and 56% (n = 105) were major resections (≥3 segments). In an intention-to-treat analysis including the dropout cases, the mortality rate was 4% and 2% in the Omegaven and placebo groups (odds ratio0.40;95% CI 0.04-2.51; p = 0.447), respectively. Any complications and major complications (Clavien-Dindo ≥ 3b) occurred in 46% vs. 43% (p = 0.709) and 12% vs. 10% (p = 0.69) in the Omegaven and placebo groups, respectively. The mean CCI was 17 (±23) vs.14 (±20) (p = 0.417). An analysis excluding the dropouts provided similar results., Conclusions: The routine perioperative use of 2 single doses of intravenous Ω3-FAs (100 ml Omegaven) cannot be recommended in patients undergoing liver surgery (Grade A recommendation)., Lay Summary: Despite strong evidence of omega-3 fatty acids having liver-directed, anti-inflammatory and pro-regenerative action in various rodent models, 2 single omega-3 fatty acid infusions given to patients before and during liver surgery failed to reduce complications. Because single omega-3 fatty acid infusions failed to confer liver protection in this trial, they cannot currently be recommended., Trial Registration: ClinicalTrial.gov: ID: NCT01884948; Institution Ethical Board Approval: KEK-ZH-Nr. 2010-0038; Swissmedic Notification: 2012DR3215., (Copyright © 2019. Published by Elsevier B.V.)

Background: Postoperative pancreatic fistula remains an unsolved challenge after pancreatoduodenectomy. Important in this regard is the presence of a soft pancreatic texture which is a major risk factor. Advances in machine learning and texture analysis of medical images allow identification of features of parenchyma that are invisible to the human eye. The aim of this study was to investigate the potential of machine learning to predict postoperative pancreatic fistula based on preoperative, non-contrast-enhanced computed tomography., Methods: We screened a prospectively assessed database including all patients undergoing pancreatoduodenectomy at a tertiary center from 2008 until 2018 for patients based on the occurrence of postoperative pancreatic fistula. In total, 110 patients were included, consisting of 55 patients who developed a postoperative pancreatic fistula and 55 without postoperative pancreatic fistula. For machine learning-based texture analysis preoperative, non-contrast-enhanced computed tomography axial images were used. Machine learning results were tested using 10-fold cross validation. Previously validated clinical fistula risk scores (original and alternative fistula risk scores) served as reference tests., Results: Both the original and the alternative fistula risk scores showed good discrimination between patients without and with postoperative pancreatic fistula (area under the curve 0.76 and 0.72, respectively). Machine learning-based texture analysis showed potential to detect histologic fibrosis (area under the curve 0.84, sensitivity 75%; specificity 92%), histologic lipomatosis (area under the curve 0.82, sensitivity 78%; specificity 89%), and intraoperative pancreatic hardness (area under the curve 0.70, sensitivity 78%; specificity 74%). The features of the machine learning-based texture analysis were most accurate in predicting the occurrence of postoperative pancreatic fistula (area under the curve 0.95, sensitivity of 96%; specificity 98%) after pancreatoduodenectomy., Conclusion: This proof-of-principle study suggests the ability of machine learning in recognizing important features of pancreatic texture associated with an increased risk of postoperative pancreatic fistula based on preoperative computed tomography., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Overweight and obese patients undergoing pancreatectomy are at increased risk for postoperative complications and readmission. We examined the association between body mass index (BMI) and postoperative complications following major pancreatectomy using the novel Comprehensive Complications Index (CCI), which analyzes the impact of multiple surgical complications rather than just the most severe., Methods: We performed a retrospective dual institutional international review of 500 consecutive patients who underwent pancreatic resection and assessed the association of BMI with postoperative complications using the CCI and Clavien-Dindo Classification (CDC) with uni- and multivariable analyses., Results: Overweight and obese patients undergoing pancreatic resection demonstrated a higher incidence and severity of CCI-measured complications (29.3 vs. 21.1, P < 0.001), more pancreatic fistulae (15.4 vs. 8.8%, 95% CI 1.005 -1.902), and an increased 30-day readmission rate (21.1 vs. 12.1%, 95% CI 1.067 -1.852) (all p < 0.05) than normal-BMI patients. The CCI was a more sensitive marker of post-pancreatectomy complications relative to the CDC, with a higher multicomplication rate in overweight/obese patients (54.8% vs. 44.5%)., Conclusion: Patients with overweight and obese body mass index undergoing major pancreatectomy demonstrated higher rates of postoperative complications, pancreatic fistulae, and readmissions. The CCI is a more robust and sensitive tool to assess post-pancreatectomy complications than the CDC., (Copyright © 2019 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Objective: To use the concept of benchmarking to establish robust and standardized outcome references after pancreatico-duodenectomy (PD)., Background: Best achievable results after PD are unknown. Consequently, outcome comparisons among different cohorts, centers or with novel surgical techniques remain speculative., Methods: This multicenter study analyzes consecutive patients (2012-2015) undergoing PD in 23 international expert centers in pancreas surgery. Outcomes in patients without significant comorbidities and major vascular resection (benchmark cases) were analyzed to establish 20 outcome benchmarks for PD. These benchmarks were tested in a cohort with a poorer preoperative physical status (ASA class ≥3) and a cohort treated by minimally invasive approaches., Results: Two thousand three hundred seventy-five (38%) low-risk cases out of a total of 6186 PDs were analyzed, disclosing low in-hospital mortality (≤1.6%) but high morbidity, with a 73% benchmark morbidity rate cumulated within 6 months following surgery. Benchmark cutoffs for pancreatic fistulas (B-C), severe complications (≥ grade 3), and failure-to-rescue rate were 19%, 30%, and 9%, respectively. The ASA ≥3 cohort showed comparable morbidity but a higher in hospital-mortality (3% vs 1.6%) and failure-to-rescue rate (16% vs 9%) than the benchmarks. The proportion of benchmark cases performed varied greatly across centers and continents for both open (9%-93%) and minimally invasive (11%-62%) PD. Centers operating mostly on complex PD cases disclosed better results than those with a majority of low-risk cases., Conclusion: The proposed outcome benchmarks for PD, established in a large-scale international patient cohort and tested in 2 different cohorts, may allow for meaningful comparisons between different patient cohorts, centers, countries, and surgical techniques.

Background: ALPPS is a two-stage hepatectomy that induces more rapid liver growth compared to conventional strategies. This report aims to establish a risk-score to avoid adverse outcomes of ALPPS only for patients with colorectal liver metastases (CRLM) as primary indication for ALPPS., Methods: All patients with CRLM included in the ALPPS registry were included. Risk score analysis was performed for 90-day mortality after ALPPS, defined as death within 90 days after either stage. Two risk scores were generated i.e. one for application before stage-1, and one for application before stage-2. Logistic regression analysis was performed to establish the risk-score., Results: In total, 486 patients were included, of which 35 (7%) died 90 days after stage-1 or 2. In the stage-1 risk score, age ≥67 years (OR 3.7), FLR/BW ratio <0.40 (OR 2.9) and total center-volume (OR 2.4) were included. For the stage-2 score age ≥67 years (OR 3.7), FLR/BW ratio <0.40 (OR 2.8), bilirubin 5 days after stage-1 >50 μmol/L (OR 2.4), and stage-1 morbidity grade IIIA or higher (OR 6.3) were included., Conclusions: The CRLM risk-score to predict mortality after ALPPS demonstrates that older patients with small remnant livers in inexperienced centers, especially after experiencing morbidity after stage-1 have adverse outcomes. The risk score may be used to restrict ALPPS to low-risk patient populations., (Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Based on the International ALPPS registry, we have recently proposed two easily applicable risk models (pre-stage1 and 2) for predicting 90-day mortality in ALPPS but a validation of both models has not been performed yet., Methods: The validation cohort (VC) was composed of subsequent cases of the ALPPS registry and cases of centers outside the ALPPS registry., Results: The VC was composed of a total of 258 patients including 70 patients outside the ALPPS registry with 32 cases of early mortalities (12%). Development cohort (DC) and VC were comparable in terms of patient and surgery characteristics. The VC validated both models with an acceptable prediction for the pre-stage 1 (c-statistic 0.64, P = 0.009 vs. 0.77, P < 0.001) and a good prediction for the pre-stage 2 model (c-statistic 0.77, P < 0.001 vs. 0.85, P < 0.001) as compared to the DC. Overall model performance measured by Brier score was comparable between VC and DC for the pre-stage 1 (0.089 vs. 0.081) and pre-stage 2 model (0.079 vs. 0087)., Conclusion: The ALPPS risk score is a fully validated model to estimate the individual risk of patients undergoing ALPPS and to assist clinical decision making to avoid procedure-related early mortality after ALPPS., (Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

: This multicentric study of 17 high-volume centers presents 12 benchmark values for liver transplantation. Those values, mostly targeting markers of morbidity, were gathered from 2024 "low risk" cases, and may serve as reference to assess outcome of single or any groups of patients., Objective: To propose benchmark outcome values in liver transplantation, serving as reference for assessing individual patients or any other patient groups., Background: Best achievable results in liver transplantation, that is, benchmarks, are unknown. Consequently, outcome comparisons within or across centers over time remain speculative., Methods: Out of 7492 liver transplantation performed in 17 international centers from 3 continents, we identified 2024 low risk adult cases with a laboratory model for end-stage liver disease score ≤20 points, a balance of risk score ≤9, and receiving a primary graft by donation after brain death. We chose clinically relevant endpoints covering intra- and postoperative course, with a focus on complications graded by severity including the complication comprehensive index (CCI). Respective benchmarks were derived from the median value in each center, and the 75 percentile was considered the benchmark cutoff., Results: Benchmark cases represented 8% to 49% of cases per center. One-year patient-survival was 91.6% with 3.5% retransplantations. Eighty-two percent of patients developed at least 1 complication during 1-year follow-up. Biliary complications occurred in one-fifth of the patients up to 6 months after surgery. Benchmark cutoffs were ≤4 days for ICU stay, ≤18 days for hospital stay, ≤59% for patients with severe complications (≥ Grade III) and ≤42.1 for 1-year CCI. Comparisons with the next higher risk group (model for end stage liver disease 21-30) disclosed an increase in morbidity but within benchmark cutoffs for most, but not all indicators, while in patients receiving a second graft from 1 center (n = 50) outcome values were all outside of benchmark values., Conclusions: Despite excellent 1-year survival, morbidity in benchmark cases remains high with half of patients developing severe complications during 1-year follow-up. Benchmark cutoffs targeting morbidity parameters offer a valid tool to assess higher risk groups.

Objective: To longitudinally assess whether risk adjustment in Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) occurred over time and is associated with postoperative outcome., Background: ALPPS is a novel 2-stage hepatectomy enabling resection of extensive hepatic tumors. ALPPS has been criticized for its high mortality, which is reported beyond accepted standards in liver surgery. Therefore, adjustments in patient selection and technique have been performed but have not yet been studied over time in relation to outcome., Methods: ALPPS centers of the International ALPPS Registry having performed ≥10 cases over a period of ≥3 years were assessed for 90-day mortality and major interstage complications (≥3b) of the longitudinal study period from 2009 to 2015. The predicted prestage 1 and 2 mortality risks were calculated for each patient. In addition, questionnaires were sent to all centers exploring center-specific risk adjustment strategies., Results: Among 437 patients from 16 centers, a shift in indications toward colorectal liver metastases from 53% to 77% and a reverse trend in biliary tumors from 24% to 9% were observed. Over time, 90-day mortality decreased from initially 17% to 4% in 2015 (P = 0.002). Similarly, major interstage complications decreased from 10% to 3% (P = 0.011). The reduction of 90-day mortality was independently associated with a risk adjustment in patient selection (P < 0.001; OR: 1.62; 95% CI: 1.36-1.93) and using less invasive techniques in stage-1 surgery (P = 0.019; OR: 0.39; 95% CI: 0.18-0.86). A survey indicated risk adjustment of patient selection in all centers and ALPPS technique in the majority (80%) of centers., Conclusions: Risk adjustment of patient selection and technique in ALPPS resulted in a continuous drop of early mortality and major postoperative morbidity, which has meanwhile reached standard outcome measures accepted for major liver surgery.

Background: Epidural analgesia (EDA) is a common analgesia regimen in liver resection, and is accompanied by sympathicolysis, peripheral vasodilatation and hypotension in the context of deliberate intraoperative low central venous pressure. This associated fall in mean arterial pressure may compromise renal blood pressure autoregulation and lead to acute kidney injury (AKI). This study investigated whether EDA is a risk factor for postoperative AKI after liver surgery., Methods: The incidence of AKI was investigated retrospectively in patients who underwent liver resection with or without EDA between 2002 and 2012. Univariable and multivariable analyses were performed including recognized preoperative and intraoperative predictors of posthepatectomy renal failure., Results: A series of 1153 patients was investigated. AKI occurred in 8·2 per cent of patients and was associated with increased morbidity (71 versus 47·3 per cent; P = 0·003) and mortality (21 versus 0·3 per cent; P <  0·001) rates. The incidence of AKI was significantly higher in the EDA group (10·1 versus 3·7 per cent; P = 0·003). Although there was no significant difference in the incidence of AKI between patients undergoing minor hepatectomy with or without EDA (5·2 versus 2·7 per cent; P = 0·421), a substantial difference in AKI rates occurred in patients undergoing major hepatectomy (13·8 versus 5·0 per cent; P = 0·025). In multivariable analysis, EDA remained an independent risk factor for AKI after hepatectomy (P = 0·040)., Conclusion: EDA may be a risk factor for postoperative AKI after major hepatectomy., (© 2015 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Objective: To assess the impact of microsteatosis (MiS) and macrosteatosis (MaS) on major hepatectomy., Summary Background Data: While steatosis of a liver graft is an established risk factor in transplantation, its impact on major hepatectomy remains unclear., Methods: Fifty-eight steatotic patients who underwent major hepatectomy were matched 1:1 with patients with normal liver according to age, gender, ASA score, diagnosis, extent of hepatectomy, and need of hepaticojejunostomy. Steatosis was evaluated quantitatively and qualitatively. Primary endpoints were mortality and complications., Results: Pure MaS and MiS were present in only 10 and 3 patients, respectively, while mixed steatosis was noted in 45 patients. Forty-four patients had mild (10%-30%) and 14 moderate/severe (>30%) steatosis. Steatotic patients had significantly higher serum transaminase and bilirubin levels, and lower prothrombin time. Blood loss (P = 0.04) and transfusions (P = 0.03), and ICU stay (P = 0.001) were increased in steatotic patients. Complications were higher in steatotic patients when considered either overall (50% vs. 25%, P = 0.007) or major (27.5% vs. 6.9%, P = 0.001) complications. Patients with pure MaS had increased mortality (MaS: 20% vs. MiS: 6.6% vs. mixed: 0%; P = 0.36) and major complications (MaS: 66% vs. MiS: 50% vs. mixed: 24%; P = 0.59), but not significantly. Preoperative cholestasis was a highly significant risk factor for mortality in patients with hepatic steatosis., Conclusion: Steatosis per se is a risk factor for postoperative complications after major hepatectomy and should be considered in the planning of surgery. Caution must be taken to perform major hepatectomy in steatotic patients with preexisting cholestasis.

The Model for End-Stage Liver Disease (MELD) system has dramatically increased the number of recipients requiring pretransplant renal replacement therapy (RRT) prior to liver transplantation (LT). Factors affecting post-LT outcomes and the need for intraoperative RRT (IORRT) were analyzed in 500 consecutive recipients receiving pretransplant RRT, including comparisons among recipients not receiving IORRT (No-IORRT, n = 401), receiving planned IORRT (Pl-IORRT, n = 70), and receiving emergent, unplanned RRT after LT initiation (Em-IORRT, n = 29). Despite a median MELD of 39, overall 30-day, 1-, 3- and 5-year survivals were 93%, 75%, 68% and 65%, respectively. Em-IORRT recipients had significantly more intraoperative complications (arrhythmias, postreperfusion syndrome, coagulopathy) compared with both No-IORRT and Pl-IORRT and greater 30-day graft loss (28% vs. 10%, p = 0.004) and need for retransplantation (24% vs. 10%, p = 0.099) compared with No-IORRT. A risk score based on multivariate predictors of IORRT accurately identified recipients with chronic (sensitivity 84%, specificity 72%, concordance-statistic [c-statistic] 0.829) and acute (sensitivity 93%, specificity 61%, c-statistic 0.776) liver failure requiring IORRT. In this largest experience of LT in recipients receiving RRT, we report excellent survival and propose a practical model that accurately identifies recipients who may benefit from IORRT. For this select group, timely initiation of IORRT reduces intraoperative complications and improves posttransplant outcomes.