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Background: Recent studies have suggested that certain combinations of KRAS or BRAF biomarkers with clinical factors are associated with poor outcomes and may indicate that surgery could be "biologically" futile in otherwise technically resectable colorectal liver metastasis (CRLM). However, these combinations have yet to be validated through external studies., Patients and Methods: We conducted a systematic search to identify these studies. The overall survival (OS) of patients with these combinations was evaluated in a cohort of patients treated at 11 tertiary centers. Additionally, the study investigated whether using high-risk KRAS point mutations in these combinations could be associated with particularly poor outcomes., Results: The recommendations of four studies were validated in 1661 patients. The first three studies utilized KRAS, and their validation showed the following median and 5-year OS: (1) 30 months and 16.9%, (2) 24.3 months and 21.6%, and (3) 46.8 months and 44.4%, respectively. When analyzing only patients with high-risk KRAS mutations, median and 5-year OS decreased to: (1) 26.2 months and 0%, (2) 22.3 months and 15.1%, and (3) not reached and 44.9%, respectively. The fourth study utilized BRAF, and its validation showed a median OS of 10.4 months, with no survivors beyond 21 months., Conclusion: The combinations of biomarkers and clinical factors proposed to render surgery for CRLM futile, as presented in studies 1 (KRAS high-risk mutations) and 4, appear justified. In these studies, there were no long-term survivors, and survival was similar to that of historic cohorts with similar mutational profiles that received systemic therapies alone for unresectable disease., (© 2024. Society of Surgical Oncology.)

To improve current data systems for institutional decision-making, the Adult Liver Transplant Registry was established at the Hospital Italiano de Buenos Aires, Argentina. This article describes its design and implementation and reports on the outcomes for patients transplanted since its January 2020 launch. A multidisciplinary team designed the registry by identifying key variables from a literature review while considering balance between data depth and feasibility. Rigorous quality control measures were enforced, including monthly audits and staff training. Benchmark indicators for post-transplant outcomes were established. As of November 2023, the registry included 136 transplants. Its implementation and maintenance were straightforward, with no significant difficulties encountered. Cirrhosis was the predominant indication (77%) for transplant. Only one living donor transplantation was performed. Post-transplant results generally aligned with benchmarks, but rates of biliary complications slightly exceeded the recommended thresholds. The one-year post-transplant survival rate was 87%. The successful registry implementation provides a robust framework for research, treatment management, and patient care enhancement within a liver transplant unit., Competing Interests: Declaration of conflicting interestsThe authors declare there are no conflicts of interest.

ALPPS enables complete tumor resection in a shorter interval and a larger number of patients than classic two-stage hepatectomies. However, there is little evidence regarding long-term outcomes in patients with colorectal liver metastases (CLM). This study aims to evaluate the short and long-term outcomes of ALPPS in patients with CRM. Single-cohort, prospective, observational study. Patients with unresectable CLM due to insufficient liver remnant who underwent ALPPS between June 2011 and June 2021 were included. Of 32 patients treated, 21 were male (66%) and the median age was 56 years (range = 29-81). Both stages were completed in 30 patients (93.7%), with an R0 rate of 75% (24/32). Major morbidity was 37.5% and the mortality nil. Median overall survival (OS) and recurrence-free survival (RFS) were 28.1 and 8.8 months, respectively. The 1-3, and 5-year OS was 86%, 45%, and 21%, and RFS was 42%, 14%, and 14%, respectively. The only independent risk factor associated with poor RFS (5.7 vs 11.6 months; p = 0.038) and OS (15 vs 37 months; p = 0.009) was not receiving adjuvant chemotherapy. KRAS mutation was associated with worse OS from disease diagnosis (24.3 vs. 38.9 months; p = 0.025). ALPPS is associated with favorable oncological outcomes, comparable to traditional strategies to increase resectability in patients with CLM and high tumor burden. Our results suggest for the first time that adjuvant chemotherapy is independently associated with better short- and long-term outcomes after ALPPS. Selection of patients with KRAS mutations should be performed with caution, as this could affect oncological outcomes., (© 2024. Italian Society of Surgery (SIC).)

Background and Aims: Alterations in liver histology influence the liver's capacity to regenerate, but the relevance of each of the different changes in rapid liver growth induction is unknown. This study aimed to analyze the influence of the degree of histological alterations during the first and second stages on the ability of the liver to regenerate., Methods: This cohort study included data obtained from the International ALPPS Registry between November 2011 and October 2020. Only patients with colorectal liver metastases were included in the study. We developed a histological risk score based on histological changes (stages 1 and 2) and a tumor pathology score based on the histological factors associated with poor tumor prognosis., Results: In total, 395 patients were included. The time to reach stage 2 was shorter in patients with a low histological risk stage 1 (13 vs 17 days, P ˂0.01), low histological risk stage 2 (13 vs 15 days, P <0.01), and low pathological tumor risk (13 vs 15 days, P <0.01). Regarding interval stage, there was a higher inverse correlation in high histological risk stage 1 group compared to low histological risk 1 group in relation with future liver remnant body weight ( r =-0.1 and r =-0.08, respectively), and future liver remnant ( r =-0.15 and r =-0.06, respectively)., Conclusions: ALPPS is associated with increased histological alterations in the liver parenchyma. It seems that the more histological alterations present and the higher the number of poor prognostic factors in the tumor histology, the longer the time to reach the second stage., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background & Aims: Malnutrition, sarcopenia, and frailty are prevalent in cirrhosis. We aimed to assess the correlation between assessment tools for malnutrition, sarcopenia, and frailty in patients on the liver transplant (LT) waiting list (WL), and to identify a predictive model for acute-on-chronic liver failure (ACLF) development., Methods: This prospective single-center study enrolled consecutive patients with cirrhosis on the WL for LT (May 2019-November 2021). Assessments included subjective global assessment, CT body composition, skeletal muscle index (SMI), ultrasound thigh muscle thickness, sarcopenia HIBA score, liver frailty index (LFI), hand grip strength, and 6-minute walk test at enrollment. Correlations were analyzed using Pearson's correlation. Competing risk regression analysis was used to assess the predictive ability of the liver- and functional physiological reserve-related variables for ACLF., Results: A total of 132 patients, predominantly with decompensated cirrhosis (87%), were included. Our study revealed a high prevalence of malnutrition (61%), sarcopenia (61%), visceral obesity (20%), sarcopenic visceral obesity (17%), and frailty (10%) among participants. Correlations between the assessment tools for sarcopenia and frailty were poor. Sarcopenia by SMI remained prevalent when frailty assessments were not usable. After a median follow-up of 10 months, 39% of the patients developed ACLF on WL, while 28% experienced dropouts without ACLF. Multivariate analysis identified MELD-Na, SMI, and LFI as independent predictors of ACLF on the WL. The predictive model MELD-Na-sarcopenia-LFI had a C-statistic of 0.85., Conclusions: The poor correlation between sarcopenia assessment tools and frailty underscores the importance of a comprehensive evaluation. The SMI, LFI, and MELD-Na independently predicted ACLF development in WL. These findings enhance our understanding of the relationship between sarcopenia, frailty, and ACLF in patients awaiting LT, emphasizing the need for early detection and intervention to improve WL outcomes., Impact and Implications: The relationship between sarcopenia and frailty assessment tools, as well as their ability to predict acute-on-chronic liver failure (ACLF) in patients on the liver transplant (LT) waiting list (WL), remains poorly understood. Existing objective frailty screening tests have limitations when applied to critically ill patients. The correlation between sarcopenia and frailty assessment tools was weak, suggesting that they may capture different phenotypes. Sarcopenia assessed by skeletal muscle index, frailty evaluated using the liver frailty index, and the model for end-stage liver disease-Na score independently predicted the development of ACLF in patients on the WL. Our findings support the integration of liver frailty index and skeletal muscle index assessments at the time of inclusion on the WL for LT. This combined approach allows for the identification of a specific patient subgroup with an increased susceptibility to ACLF, underscoring the importance of early implementation of targeted treatment strategies to improve outcomes for patients awaiting LT., Competing Interests: All authors declare no conflicts of interest for this study. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2023 The Author(s).)

Background: The aim of this study is to analyze the role of neutrophil-lymphocyte ratio (NLR) and its variation pre- and postoperatively (delta NLR) in the overall survival after pancreatectomy for pancreatic ductal adenocarcinoma (PDAC) at a single center and to identify factors associated with overall survival., Methods: A retrospective study of consecutive patients undergoing pancreatectomy due to PDAC or undifferentiated carcinoma from January 2010 to January 2020 was performed. Association between the evaluated factors and overall survival was analyzed using a log-rank test and Cox proportional hazard regression model., Results: Overall, 242 patients underwent pancreatectomy for PDAC or undifferentiated carcinoma. OS was 22.8 months (95% confidence interval (CI): 19.5-29), and survival rates at 1, 3, and 5 years were 72%, 32.5%, and 20.8%, respectively. NLR and delta NLR were not significantly associated with survival (hazard ratio (HR) = 1.14, 95%CI: 0.77-1.68, p = 0.5). Lymph node ratio was significantly associated (HR = 1.66, 95%CI: 1.21-2.26, p = 0.001) in the bivariate analysis. In multivariable analysis, the only factors that were significantly associated with survival were perineural invasion (HR = 1.94, 95%CI: 1.21-3.14, p = 0.006), surgical margin (HR = 1.83, 95%CI: 1.10-3.02, p = 0.019), tumor size (HR = 1.01, 95%CI: 1.003-1.027, p = 0.16), postoperative CA 19-9 level (HR = 1.001, p < 0.001), and completion of adjuvant treatment (HR = 0.53, 95%CI: 0.35-0.8, p = 0.002)., Conclusion: Neutrophil-lymphocyte ratio and delta NLR were not associated with the overall survival in this cohort. Risk factors such as perineural invasion, surgical margins, CA19-9 level, and tumor size showed worse survival in this study, whereas completing adjuvant treatment was a protective factor., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Colorectal cancer is the third most common cancer worldwide, and up to 50% of all patients diagnosed will develop metastatic disease. Management of colorectal liver metastases (CRLM) has been constantly improving, aided by newer and more effective chemotherapy agents and the use of multidisciplinary teams. However, the only curative treatment remains surgical resection of the CRLM. Although survival for surgically resected patients has shown modest improvement, this is mostly because of the fact that what is constantly evolving is the indication for resection. Surgeons are constantly pushing the limits of what is considered resectable or not, thus enhancing and enlarging the pool of patients who can be potentially benefited and even cured with aggressive surgical procedures. There are a variety of procedures that have been developed, which range from procedures to stimulate hepatic growth, such as portal vein embolization, two-staged hepatectomy, or the association of both, to technically challenging procedures such as simultaneous approaches for synchronous metastasis, ex-vivo or in-situ perfusion with total vascular exclusion, or even liver transplant. This article reviewed the major breakthroughs in liver surgery for CRLM, showing how much has changed and what has been achieved in the field of CRLM.

Pancreatic ductal adenocarcinoma remains a global health challenge and is predicted to soon become the second leading cause of cancer death in developed countries. Currently, surgical resection in combination with systemic chemotherapy offers the only chance of cure or long-term survival. However, only 20% of cases are diagnosed with anatomically resectable disease. Neoadjuvant treatment followed by highly complex surgical procedures has been studied over the last decade with promising short- and long-term results in patients with locally advanced pancreatic ductal adenocarcinoma (LAPC). In recent years, a wide variety of complex surgical techniques that involve extended pancreatectomies, including portomesenteric venous resection, arterial resection, or multi-organ resection, have emerged to optimize local control of the disease and improve postoperative outcomes. Although there are multiple surgical techniques described in the literature to improve outcomes in LAPC, the comprehensive view of these strategies remains underdeveloped. We aim to describe the preoperative surgical planning as well different surgical resections strategies in LAPC after neoadjuvant treatment in an integrated way for selected patients with no other potentially curative option other than surgery.

Background: Resident involvement in the operating room is a vital component of their medical education. Laparoscopic cholecystectomy (LC) represents the paradigmatic minimally invasive training procedure, both due to its prevalence and its different forms of complexity. We aim to evaluate whether the supervised participation of residents as operative surgeons in LC of different degrees of complexity affects postoperative outcomes in a university hospital., Methods: This is a retrospective, single-center study that included all consecutive adult (> 18 years old) patients operated for a LC between January 1, 2012 and December 31, 2017. Each surgical procedure was recorded according to the level of complexity that we established in three types of categorization (level 1: elective surgery; level 2: cholecystitis; level 3: biliary instrumentation). Patients were clinically monitored at an outpatient clinic 7 and 30-day postoperative. Postoperative outcomes of patients operated by supervised residents (SR) and trained surgeons (TS) were compared. Postoperative complications were graded according to the Clavien-Dindo classification of surgical complications., Results: A total of 2331 patients underwent LC during the study period, of whom 1573 patients (67.5%) were operated by SR and 758 patients (32.5%) by TS. There were no significant differences among age, sex, and BMI between patients operated in both groups, with the exception of ASA (P = 0.0001). Intraoperative cholangiography was performed in 100% of the patients, without bile duct injuries. There were no deaths in the 30 postoperative days. The overall complication rate was 5.70% (133 patients), with no significant differences when comparing LC performed by SR and TS (5.09 vs. 6.99%; P = 0.063). The severity rates of complications were similar in both groups (P = 0.379). Patient readmission showed a statistical difference comparing SR vs TS (0.76% vs. 2.2%; P = 0.010). The postoperative complications rate according to the complexity level of LC was not significant in level 1 and 2 for both groups. However in complexity level 3 the TS group experienced a greater rate of complications compared to the SR group (18.12% vs. 9.38%; P = 0.058). In the multivariate analysis, the participation of the residents as operating surgeons was not independently associated with an increased risk of complications (OR 1.22, 95% CI 0.84-1.77; P = 0.275), neither other risk factors like age ≥ 65 years, BMI, complexity level 2-3, or ASA ≥ 3-4. The association of another surgical procedure with the LC was an independent factor of morbidity (OR 3.85, 95% CI 2.54-5.85; P = 0.000)., Conclusion: Resident involvement in LC with different degrees of complexity did not affect postoperative outcomes. The participation of a resident as operating surgeon is not an independent risk factor and may be considered ethical, safe, and reliable whenever implemented in the background of a residency-training program with continuous supervision and national accreditation. The sum of other procedures not related to a LC should be taken as a risk factor of morbidity., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: While ALPPS triggers a fast liver hypertrophy, it is still unclear which factors matter most to achieve accelerated hypertrophy within a short period of time. The aim of the study was to identify patient-intrinsic factors related to the growth of the future liver remnant (FLR)., Methods: This cohort study is composed of data derived from the International ALPPS Registry from November 2011 and October 2018. We analyse the influence of demographic, tumour type and perioperative data on the growth of the FLR. The volume of the FLR was calculated in millilitre and percentage using computed-tomography (CT) scans before and after stage 1, both according to Vauthey formula., Results: A total of 734 patients were included from 99 centres. The median sFLR at stage 1 and stage 2 was 0.23 (IQR, 0.18-0.28) and 0.39 (IQR: 0.31-0.46), respectively. The variables associated with a lower increase from sFLR1 to sFLR2 were age˃68 years (p = .02), height ˃1.76 m (p ˂ .01), weight ˃83 kg (p ˂ .01), BMI˃28 (p ˂ .01), male gender (p ˂ .01), antihypertensive therapy (p ˂ .01), operation time ˃370 minutes (p ˂ .01) and hospital stay˃14 days (p ˂ .01). The time required to reach sufficient volume for stage 2, male gender accounts 40.3% in group ˂7 days, compared with 50% of female, and female present 15.3% in group ˃14 days compared with 20.6% of male., Conclusions: Height, weight, FLR size and gender could be the variables that most constantly influence both daily growths, the interstage increase and the standardized FLR before the second stage., (© 2022 The Authors. Liver International published by John Wiley & Sons Ltd.)

Objective: To define benchmark cutoffs for redo liver transplantation (redo-LT)., Background: In the era of organ shortage, redo-LT is frequently discussed in terms of expected poor outcome and wasteful resources. However, there is a lack of benchmark data to reliably evaluate outcomes after redo-LT., Methods: We collected data on redo-LT between January 2010 and December 2018 from 22 high-volume transplant centers. Benchmark cases were defined as recipients with model of end stage liver disease (MELD) score ≤25, absence of portal vein thrombosis, no mechanical ventilation at the time of surgery, receiving a graft from a donor after brain death. Also, high-urgent priority and early redo-LT including those for primary nonfunction (PNF) or hepatic artery thrombosis were excluded. Benchmark cutoffs were derived from the 75th percentile of the medians of all benchmark centers., Results: Of 1110 redo-LT, 373 (34%) cases qualified as benchmark cases. Among these cases, the rate of postoperative complications until discharge was 76%, and increased up to 87% at 1-year, respectively. One-year overall survival rate was excellent with 90%. Benchmark cutoffs included Comprehensive Complication Index CCI ® at 1-year of ≤72, and in-hospital and 1-year mortality rates of ≤13% and ≤15%, respectively. In contrast, patients who received a redo-LT for PNF showed worse outcomes with some values dramatically outside the redo-LT benchmarks., Conclusion: This study shows that redo-LT achieves good outcome when looking at benchmark scenarios. However, this figure changes in high-risk redo-LT, as for example in PNF. This analysis objectifies for the first-time results and efforts for redo-LT and can serve as a basis for discussion about the use of scarce resources., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: To explore potential sex differences in outcomes and regenerative parameters post major hepatectomies., Background: Although controversial, sex differences in liver regeneration have been reported for animals. Whether sex disparity exists in human liver regeneration is unknown., Methods: Data from consecutive hepatectomy patients (55 females, 67 males) and from the international ALPPS (Associating-Liver-Partition-and-Portal-vein-ligation-for-Staged-hepatectomy, a two stage hepatectomy) registry (449 females, 729 males) were analyzed. Endpoints were severe morbidity (≥3b Clavien-Dindo grades), Model for End-stage Liver Disease (MELD) scores, and ALPPS interstage intervals. For validation and mechanistic insight, female-male ALPSS mouse models were established. t , χ 2 , or Mann-Whitney tests were used for comparisons. Univariate/multivariate analyses were performed with sensitivity inclusion., Results: Following major hepatectomy (Hx), males had more severe complications ( P =0.03) and higher liver dysfunction (MELD) P =0.0001) than females. Multivariate analysis established male sex as a predictor of complications after ALPPS stage 1 (odds ratio=1.78; 95% confidence interval: 1.126-2.89; P =0.01), and of enhanced liver dysfunction after stage 2 (odds ratio=1.93; 95% confidence interval: 1.01-3.69; P =0.045). Female patients displayed shorter interstage intervals (<2 weeks, 64% females versus 56% males, P =0.01), however, not in postmenopausal subgroups. In mice, females regenerated faster than males after ALPPS stage 1, an effect that was lost upon estrogen antagonism., Conclusions: Poorer outcomes after major surgery in males and shorter ALPPS interstage intervals in females not necessarily suggest a superior regenerative capacity of female liver. The loss of interstage advantages in postmenopausal women and the mouse experiments point to estrogen as the driver behind these sex disparities. Estrogen's benefits call for an assessment in postmenopausal women, and perhaps men, undergoing major liver surgery., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Liver transplantation is an extremely complex procedure performed in an extremely complex patient. With a successful technique and acceptable long-term survival, a new challenge arose: overcoming donor shortage. Thus, living donor liver transplant and other techniques were developed. Aiming for donor safety, many liver transplant units attempted to push the viable limits in terms of size, retrieving smaller and smaller grafts for adult recipients. With these smaller grafts came numerous problems, concepts, and definitions. The spotlight is now aimed at the mirage of hemodynamic changes derived from the recipients prior alterations. This article focuses on the numerous hemodynamic syndromes, their definitions, causes, and management and interconnection with each other. The aim is to aid the physician in their recognition and treatment to improve liver transplantation success., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2022 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Importance: In patients with resectable colorectal cancer liver metastases (CRLM), the choice of surgical technique and resection margin are the only variables that are under the surgeon's direct control and may influence oncologic outcomes. There is currently no consensus on the optimal margin width., Objective: To determine the optimal margin width in CRLM by using artificial intelligence-based techniques developed by the Massachusetts Institute of Technology and to assess whether optimal margin width should be individualized based on patient characteristics., Design, Setting, and Participants: The internal cohort of the study included patients who underwent curative-intent surgery for KRAS-variant CRLM between January 1, 2000, and December 31, 2017, at Johns Hopkins Hospital, Baltimore, Maryland, Memorial Sloan Kettering Cancer Center, New York, New York, and Charité-University of Berlin, Berlin, Germany. Patients from institutions in France, Norway, the US, Austria, Argentina, and Japan were retrospectively identified from institutional databases and formed the external cohort of the study. Data were analyzed from April 15, 2019, to November 11, 2021., Exposures: Hepatectomy., Main Outcomes and Measures: Patients with KRAS-variant CRLM who underwent surgery between 2000 and 2017 at 3 tertiary centers formed the internal cohort (training and testing). In the training cohort, an artificial intelligence-based technique called optimal policy trees (OPTs) was used by building on random forest (RF) predictive models to infer the margin width associated with the maximal decrease in death probability for a given patient (ie, optimal margin width). The RF component was validated by calculating its area under the curve (AUC) in the testing cohort, whereas the OPT component was validated by a game theory-based approach called Shapley additive explanations (SHAP). Patients from international institutions formed an external validation cohort, and a new RF model was trained to externally validate the OPT-based optimal margin values., Results: This cohort study included a total of 1843 patients (internal cohort, 965; external cohort, 878). The internal cohort included 386 patients (median [IQR] age, 58.3 [49.0-68.7] years; 200 men [51.8%]) with KRAS-variant tumors. The AUC of the RF counterfactual model was 0.76 in both the internal training and testing cohorts, which is the highest ever reported. The recommended optimal margin widths for patient subgroups A, B, C, and D were 6, 7, 12, and 7 mm, respectively. The SHAP analysis largely confirmed this by suggesting 6 to 7 mm for subgroup A, 7 mm for subgroup B, 7 to 8 mm for subgroup C, and 7 mm for subgroup D. The external cohort included 375 patients (median [IQR] age, 61.0 [53.0-70.0] years; 218 men [58.1%]) with KRAS-variant tumors. The new RF model had an AUC of 0.78, which allowed for a reliable external validation of the OPT-based optimal margin. The external validation was successful as it confirmed the association of the optimal margin width of 7 mm with a considerable prolongation of survival in the external cohort., Conclusions and Relevance: This cohort study used artificial intelligence-based methodologies to provide a possible resolution to the long-standing debate on optimal margin width in CRLM.

Sarcopenia is a prevalent condition that predicts prognosis in patients awaiting liver transplantation (LT). The gold standard for the diagnosis of sarcopenia is the assessment of the muscular area at L3 with computed tomography (CT) scan (skeletal muscle index [SMI]), but the routine use of CT scan is limited in clinical practice. Thus, we designed a single-center observational study aimed to evaluate the clinical factors associated with the presence of sarcopenia by SMI, and to build a score capable of predicting or excluding the presence of sarcopenia in patients on the LT waiting list (WL). Binary logistic regression analysis was performed to establish the factors independently associated with sarcopenia, and the Sarcopenia Hospital Italiano de Buenos Aires (HIBA) score was built from the resulting model after internal validation analysis by bootstrapping and correction for optimism. The predictive capability of mortality on the WL was evaluated with competing risk regression analysis. A total of 215 patients with cirrhosis on the LT WL were included. The independent factors associated with the presence of sarcopenia were male sex (odds ratio [OR]: 6.09, p < 0.001), body mass index (OR: 0.74, p < 0.001), Child Pugh (OR: 1.44, p < 0.001), and the ratio creatinine/Cystatin C (OR: 0.03, p = 0.007). The Sarcopenia HIBA score constructed with these variables showed an area under the curve of 0.862. During follow-up, 77 (36%) patients underwent LT, 46 (21%) died, and 92 (43%) remained alive. After adjusting for Model for End-Stage Liver Disease-Sodium, Sarcopenia HIBA score was an independent predictor of WL mortality (subhazard ratio: 1.19; 95% confidence interval 1.01-1.40; p = 0.042). Sarcopenia HIBA score is an easy-to-use, objective, and reliable diagnostic and predictive tool that can be useful to improve the prognostic evaluation and allow identifying a group of patients with a higher risk of death while awaiting LT., (© 2022 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Background: Liver resection represents the curative treatment of choice for patients with colorectal liver metastases (CRLM). Laparoscopic hepatectomy in CRLM is considered a safe approach. However, the information on their oncological results in the different series is deficient. This study aimed to compare the surgical margin, overall survival (OS), and disease-free survival (DFS) in patients with oncological resections of CRLM according to the type of surgical approach performed., Methods: Between April 2007 and June 2017, 263 patients with CRLM underwent hepatic resection. Inclusion criteria were initial resectability, tumor size ≤ 50 mm, 3 or less metastases, no bilobar involvement, and absence of extrahepatic disease. A propensity score was performed to adjust the indication bias., Results: Eighty-two patients were included (56 open and 26 laparoscopic). Twenty-eight (50%) patients had synchronous presentation in the open approach and 6 (23%) in the laparoscopic approach (p = 0.021), with more frequent simultaneous open resections (p = 0.037). The resection margin was positive (R1) in 5 patients with an open approach and 2 with a laparoscopic approach (8.9% and 7.6% respectively; p = 0.852). Nine patients (16%) with conventional approach and 2 (7.7%) with laparoscopic approach had local complications (p = 0.3). There was one death in the open group and none in the laparoscopic. There were no significant differences in OS and DFS rate between both groups (1-3 years, OS: 92-77% and 96-75% respectively; 1-3 years, DFS: 63-20% and 73-36% respectively)., Conclusions: There were no significant differences in terms of surgical margin, OS rate, and DFS rate between the laparoscopic and open approach in patients with CRLM., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: The aim of this study was to report the long-term results of an institutional protocol of percutaneous biliary balloon dilatation (PBBD) on paediatric patients with benign anastomotic stricture after liver transplantation. As a secondary objective, we evaluated risk factors associated with post-treatment re-stricture., Materials and Methods: Fourteen paediatric, post-liver transplant patients with benign anastomotic stricture of Roux-en-Y hepaticojejunostomy were included. All patients underwent the same treatment protocol of three PBBD procedures with 15-day intervals. Clinical outcome was analysed using the Terblanche classification. Primary patency rate was assessed with the Kaplan-Meier test., Results: All patients had an initial successful result (Terblanche grade, excellent/good) after PBBD. At the end of the follow-up time of 35.7 ± 21.1 months (CI95%, 23.5-47.9), 10 patients persisted with excellent/good grading, while the remaining 4 had re-stricture, all of the latter occurring within the first 19 months. Patency rate after percutaneous treatment at 1, 3, and 5 years were 85.7%, 70%, and 70%, respectively. History of major complication after liver transplantation was associated with 5 times higher risk of re-stricture, HR 5.48 [95% CI, 2.18-8.78], p = 0.018., Conclusion: In paediatric patients with benign anastomotic stricture of hepaticojejunostomy after liver transplantation, the "Three-session" percutaneous biliary balloon dilatation protocol is associated with a high rate of long-term success. In this limited series, the history of post-liver transplant major complication, defined as complications requiring a reintervention under general anaesthesia or advanced life support, seems to be an independent risk factor for stricture recurrence., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).)

Backgrounds/aims: The role of inflammation in malignant cell proliferation has been well described. High values of platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) as markers of systemic inflammation have shown associations with unfavorable long-term outcomes. The purpose of this study was to determine values of NLR and PLR evaluated prior to and after surgery and their associations with mortality and recurrence rates of liver transplant patients with hepatocellular carcinoma (HCC)., Methods: A total of 105 patients with HCC who underwent orthotopic liver transplantation (OLT) were retrospectively reviewed. NLR and PLR values were obtained from complete blood counts prior to and after surgery. Overall survival (OS) and recurrence-free survival (RFS) in relation with delta NLR and PLR were estimated., Results: Serum alpha-fetoprotein levels > 100 ng/mL ( p = 0.014) and lymphovascular emboli in the specimen ( p = 0.048) were identified to be significant predictors of RFS. Child-Pugh score ( p = 0.016) was found to be an independent factor associated with poorer OS. An increasing delta PLR was associated with worse RFS, although it showed no significant association with OS., Conclusions: The analysis of PLR as a continuous variable may predict recurrence outcomes in patients undergoing OLT for HCC. It is more representative than isolated values.

Hepatocellular carcinoma is the most common primary liver tumor, with 905 677 diagnosed cases and 830 180 deaths, in 2020 worldwide. In Argentina, it accounts for the 9th cause of death for cancer in men and the 10th in women. Unlike other highly-prevalent tumors, scientific evidence for most therapeutic options is limited mainly to small cohorts and retrospective studies. The aim of this study is to characterize and describe epidemiologically patients with diagnosis of hepatocellular carcinoma in the Italian Hospital of Buenos Aires during a 12-year period. Overall survival for our cohort was 58%, 46%, and 36% at 1, 3 and 5 years respectively. Average survival for patients receiving palliative treatment was 5 months, while for those who received either non-curative or curative treatment was 23 and 75 months respectively. Recurrence-free survival for those patients who underwent a curative treatment was 89%, 76% y 61% at 1, 3 and 5 years. A thorough analysis of etiology, risk factors, incidence, mortality and treatment was made. The study's importance lies in its large sample size, quantity and quality of data, and will most certainly stimulate the development of local studies in hepatocellular carcinoma.

Background: Acute biliary pancreatitis (ABP) is often associated with persistent common bile duct (CBD) stones. The best strategy in terms of timing of surgery is still controversial. The aim of the current study is to describe the prevalence of persistent common bile duct (CBD) stones in ABP during the first week of symptoms at a high-volume referral center., Study Design: Single-institution retrospective analysis of a prospectively collected database. Patients with diagnosis of ABP who underwent laparoscopic cholecystectomy (LC) between January 2009 and December 2019 were extracted., Results: Two hundred thirty-one patients were included. Cholecystectomy was performed laparoscopically in 230 (99.57%) patients. Intraoperative cholangiogram was performed in all patients. Two hundred nine (90%) patients had surgery within the first 7 days. Global prevalence of persistent CBD stones during IOC was 19.91% (95% CI 14.96-25.65). No significant association between timing to surgery and presence of CBD stones was found for the first week since the initial attack (p=0.28). Prevalence of CBD stones was significantly higher after day 7 (p=0.007 and 0.005). Positive findings in preoperative MRCP are significantly related to intraoperative CBD stones (p=0.0001). Mild postoperative complications (CD I/II) were present in 21 patients (9.09%). No difference was found in morbidity between CBD stones group and non-CBD stones group (p=0.48). We observed no severe complications nor mortality., Conclusions: In patients with mild acute biliary pancreatitis, the prevalence of persistent CBD stones does not change within the first 7 days since the onset of symptoms. This fact may have major clinical relevance when deciding the optimal therapeutic strategy in this population., (© 2021. The Society for Surgery of the Alimentary Tract.)

Objective: The aim of this study was to evaluate whether neoadjuvant therapy (NAT) critically influenced microscopically complete resection (R0) rates and long-term outcomes for patients with pancreatic ductal adenocarcinoma who underwent pancreatoduodenectomy (PD) with portomesenteric vein resection (PVR) from a diverse, world-wide group of high-volume centers., Summary of Background Data: Limited size studies suggest that NAT improves R0 rates and overall survival compared to upfront surgery in R/BR-PDAC patients., Methods: This multicenter study analyzed consecutive patients with R/BR-PDAC who underwent PD with PVR in 23 high-volume centers from 2009 to 2018., Results: Data from 1192 patients with PD and PVR were collected and analyzed. The median age was 68 [interquartile range (IQR) 60-73] years and 52% were males. Some 186 (15.6%) and 131 (10.9%) patients received neoadjuvant chemotherapy (NAC) alone and neoadjuvant chemoradiotherapy, respectively. The R0/R1/R2 rates were 57%, 39.3%, and 3.2% in patients who received NAT compared to 46.6%, 49.9%, and 3.5% in patients who did not, respectively (P =0.004). The 1-, 3-, and 5-year OS in patients receiving NAT was 79%, 41%, and 29%, while for those that did not it was 73%, 29%, and 18%, respectively (P <0.001). Multivariable analysis showed no administration of NAT, high tumor grade, lymphovascular invasion, R1/R2 resection, no adjuvant chemotherapy, occurrence of Clavien-Dindo grade 3 or higher postoperative complications within 90 days, preoperative diabetes mellitus, male sex and portal vein involvement were negative independent predictive factors for OS., Conclusion: Patients with PDAC of the pancreatic head expected to undergo venous reconstruction should routinely be considered for NAT., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The aim of this study was to determine the effect of hyperbilirubinemia in the sensitivity of percutaneous transluminal forceps biopsy (PTFB) in patients with suspected malignant biliary stricture., Materials and Methods: Ninety-three patients with suspicion of malignant biliary stricture underwent percutaneous transhepatic cholangiography followed by PTFB. Sensitivity, specificity and predictive values were analysed based on the presence or absence of hyperbilirubinemia, defined as total bilirubin equal to, or higher than 5 mg/dL. Variables included demographic and clinical features, laboratory, tumour type and localization, stricture length, therapeutic approach and histopathology. Additionally, major morbidity and mortality were assessed., Results: The overall sensitivity, specificity, positive predictive value and accuracy of PTFB were 61.1%, 100%, 100%, and 62.4%, respectively. Hyperbilirubinemia affected 57% of patients at the time of PTFB. There were 35 (37%) false negative results, none of them related to tumour type or localization, stricture length, or previous biliary intervention (i.e. PBBD (percutaneous biliary balloon dilatation), ERCP (endoscopic retrograde cholangiopancreatography)) (p > 0.05). However, when bilirubin was < 5 mg/dL, false negative results decreased globally (p = 0.024) and sensitivity increased significantly for intrahepatic and hilar localization, as well as for colorectal metastasis, gallbladder carcinoma, and pancreatic carcinoma. No major morbidity occurred., Conclusion: The sensitivity of percutaneous transluminal biopsy for diagnosis of malignant stricture may significantly increase if samples are obtained in the absence of hyperbilirubinemia, without adding morbidity to the procedure., Level of Evidence: Level 3, Case- Control studies., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).)

Background: Repeated liver resections for the recurrence of colorectal liver metastasis (CRLM) are described as safe and have similar oncological outcomes compared to first hepatectomy. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is performed in patients with conventionally non-resectable CRLM. Repeated resections after ALPPS has not yet been described., Methods: Patients that underwent repeated liver resection in recurrence of CRLM after ALPPS were included in this study. The primary endpoint was morbidity and secondary endpoints were mortality, resection margin and survival., Results: Thirty patients were included in this study. During ALPPS, most of the patients had classical split (60%, n = 18) and clearance of the FLR (77%, n = 23). Hepatic recurrence was treated with non-anatomical resection (57%, n = 17), resection combined with local ablation (13%, n = 4), open ablation (13%, n = 4), segmentectomy (10%, n = 3) or subtotal segmentectomy (7%, n = 2). Six patients (20%) developed complications (10% minor complications). No post-hepatectomy liver failure or perioperative mortality was observed. One-year patient survival was 87%. Five patients received a third hepatectomy., Conclusion: Repeated resections after ALPPS for CRLM in selected patients are safe and feasible with low morbidity and no mortality. Survival seems to be comparable with repeated resections after conventional hepatectomy., (Copyright © 2021 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Competing Interests: The authors report no conflicts of interest.

Introduction: Two novel clinical risk scores (CRS) that incorporate KRAS mutation status were developed: modified CRS (mCRS) and GAME score. However, they have not been tested in large national and international cohorts. The aim of this study was to validate the prognostic discrimination utility and determine the clinical usefulness of the two novel CRS., Methods: Patients undergoing hepatectomy for CRLM (2000-2018) in 10 centers were included. The discriminatory abilities of mCRS, GAME, and Fong CRS were evaluated using Harrell's C-index and Akaike's Information Criterion., Results: In the entire cohort, the C-index of the GAME score (0.61) was significantly higher than those of Fong score (0.57) and mCRS (0.54), while the C-Index of mCRS was significantly lower than that of Fong score. When we compared the models in the various geographical regions, the C-index of GAME score was significantly higher than that of mCRS in North America, Europe, and South America. The AIC of Fong score, mCRS, and GAME score were 14 405, 14 447, and 14 319, respectively., Conclusion: In conclusion, using the largest and most heterogenous population of CRLM patients with known KRAS status, this independent, external validation demonstrated that the GAME score outperforms both the traditional Fong score and mCRS., (© 2021 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Liver metastases are commonly detected in a range of malignancies including colorectal cancer (CRC), pancreatic cancer, melanoma, lung cancer and breast cancer, although CRC is the most common primary cancer that metastasizes to the liver. Interactions between tumour cells and the tumour microenvironment play an important part in the engraftment, survival and progression of the metastases. Various cells including liver sinusoidal endothelial cells, Kupffer cells, hepatic stellate cells, parenchymal hepatocytes, dendritic cells, resident natural killer cells as well as other immune cells such as monocytes, macrophages and neutrophils are implicated in promoting and sustaining metastases in the liver. Four key phases (microvascular, pre-angiogenic, angiogenic and growth phases) have been identified in the process of liver metastasis. Imaging modalities such as ultrasonography, CT, MRI and PET scans are typically used for the diagnosis of liver metastases. Surgical resection remains the main potentially curative treatment among patients with resectable liver metastases. The role of liver transplantation in the management of liver metastasis remains controversial. Systemic therapies, newer biologic agents (for example, bevacizumab and cetuximab) and immunotherapeutic agents have revolutionized the treatment options for liver metastases. Moving forward, incorporation of genetic tests can provide more accurate information to guide clinical decision-making and predict prognosis among patients with liver metastases.

Background: The management of Branch-Duct Intraductal Papillary Mucinous Neoplasm (BD-IPMN) is still controversial. Our objective was to assess the long-term follow-up (FU) of patients with "low-risk" BD-IPMN according to the Sendai-International Consensus Guidelines (ICG-I)., Methods: We retrospectively analyzed a cohort of patients with BD-IPMN and Negative Sendai-Criteria (NSC) from January 2004 to October 2019. A univariate analysis was performed to determine factors associated with conversion to Positive Sendai-Criteria (PSC) and malignancy. Positive Predictive Value (PPV) and Negative Predictive Value (NPV) of the IGC-I were assessed for the development of malignancy., Results: A total of 219 patients were selected and underwent a median 58-month FU. Thirty-seven (17%) patients developed PSC during FU including 12 (5.5%) with malignant lesions. Conversely, 182 patients (83%) did not develop malignancy. The NPV and PPV of ICG-I for malignancy were 100% and 32.4%, respectively. Among patients who developed PSC, those with cancer were >65years (OR = 3.57;p = 0.015) and had significantly higher serum CA-19-9 levels (OR = 5.27;p = 0.007)., Conclusion: The ICG-I is a safe strategy for FU of patients with BD-IPMN. The absence of PSC exclude malignancy. Among patients who develops PSC, the risk of cancer remains low and surgery should be decided according to their surgical risk and life expectancy., (Copyright © 2020 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Pancreatic cancer is an aggressive disease associated with poor results regarding long term survival. Surgical treatment along with new oncologic treatments have improved the survival of these patients in international experience reports. The aim of this study was to describe overall survival and disease-free survival after pancreatectomy for pancreatic ductal adenocarcinoma. A retrospective study of consecutive patients undergoing pancreatic resection due to PDAC or undifferentiated carcinoma from January 2010 to January 2020 in a single tertiary center was performed. Overall, 242 patients underwent complete pancreatic resections for pancreatic ductal adenocarcinoma or undifferentiated carcinoma. Median overall survival was 22.8 months (95% CI: 19.5-29) and survival at 1, 3 and 5 years were 72%, 32.5% and 20.8% respectively. The median disease-free survival was 13.8 months (95% CI: 12-17.6) and 1, 3- and 5-years disease-free survival were 56.1%, 21.8% and 19.4% respectively. The groups of patients that completed adjuvant treatment showed a better overall survival (p < 0.0001).

Background: Liver transplantation (LT) has been used as a last resort in patients with end-stage liver disease due to bile duct injuries (BDI) following cholecystectomy. Our study aimed to identify and evaluate factors that cause or contribute to an extended liver disease that requires LT as ultimate solution, after BDI during cholecystectomy., Methods: Data from 8 high-volume LT centers relating to patients who underwent LT after suffering BDI during cholecystectomy were prospectively collected and retrospectively analyzed., Results: Thirty-four patients (16 men, 18 women) with a median age of 45 (range 22-69) years were included in this study. Thirty of them (88.2%) underwent LT because of liver failure, most commonly as a result of secondary biliary cirrhosis. The median time interval between BDI and LT was 63 (range 0-336) months. There were 23 cases (67.6%) of postoperative morbidity, 6 cases (17.6%) of post-transplant 30-day mortality, and 10 deaths (29.4%) in total after LT. There was a higher probability that patients with concomitant vascular injury (hazard ratio 10.69, P=0.039) would be referred sooner for LT. Overall survival following LT at 1, 3, 5 and 10 years was 82.4%, 76.5%, 73.5% and 70.6%, respectively., Conclusion: LT for selected patients with otherwise unmanageable BDI following cholecystectomy yields acceptable long-term outcomes., Competing Interests: Conflict of Interest: None, (Copyright: © 2021 Hellenic Society of Gastroenterology.)

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) approach emerged as a promising surgical strategy for rapid and large hypertrophy of the future liver remnant (FLR) when a major liver resection is necessary. Colorectal liver metastasis (CRLM) is their main indication. However, the promising results published so far, are very difficult to interpret since they usually focus on the technique and not on the underlying disease. Moreover, they are usually made up of complex populations, which received different chemotherapy schemes, with the ALPPS technical variations implemented over time and without consistent long-term follow-up results as well. Whereby, its role in CRLM should be analyzed as carefully as possible to indicate and select the best candidates who will benefit the most from this approach. We conducted a computerized search using PubMed and Google Scholar for reports published so far, using mesh headings and keywords related to the ALPPS and CRLM., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/hbsn.2019.08.03). The authors have no conflicts of interest to declare., (2020 Hepatobiliary Surgery and Nutrition. All rights reserved.)

Objective: To test the degree of agreement in selecting therapeutic options for patients suffering from colorectal liver metastasis (CRLM) among surgical experts around the globe., Summary/background: Only few areas in medicine have seen so many novel therapeutic options over the past decades as for liver tumors. Significant variations may therefore exist regarding the choices of treatment, even among experts, which may confuse both the medical community and patients., Methods: Ten cases of CRLM with different levels of complexity were presented to 43 expert liver surgeons from 23 countries and 4 continents. Experts were defined as experienced surgeons with academic contributions to the field of liver tumors. Experts provided information on their medical education and current practice in liver surgery and transplantation. Using an online platform, they chose their strategy in treating each case from defined multiple choices with added comments. Inter-rater agreement among experts and cases was calculated using free-marginal multirater kappa methodology. A similar, but adjusted survey was presented to 60 general surgeons from Asia, Europe, and North America to test their attitude in treating or referring complex patients to expert centers., Results: Thirty-eight (88%) experts completed the evaluation. Most of them are in leading positions (92%) with a median clinical experience of 25 years. Agreement on therapeutic strategies among them was none to minimal in more than half of the cases with kappa varying from 0.00 to 0.39. Many general surgeons may not refer the complex cases to expert centers, including in Europe, where they also engage in complex liver surgeries., Conclusions: Considerable inconsistencies of decision-making exist among expert surgeons when choosing a therapeutic strategy for CRLM. This might confuse both patients and referring physicians and indicate that an international high-level consensus statements and widely accepted guidelines are needed.

Background: Impaired postoperative renal function is associated with increased morbidity and mortality after liver resection. The role of impaired renal function in the two-stage hepatectomy setting of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is unknown., Methods: An international multicenter cohort of ALPPS patients captured in the ALPPS Registry was analyzed. Particular attention was drawn to the renal function in the interstage interval to determine outcome after stage 2 surgery. Interstage renal impairment (RI) was defined as an increase of serum creatinine of ≥ 0.3 mg/dl referring to a preoperative value or an increase of serum creatinine of ≥ 1.5× of the preoperative value on the fifth postoperative day after stage 1., Results: A total of 705 patients were identified of which 7.5% had an interstage RI. Patients developing an interstage RI were significantly older. During stage 1, a longer operation time, higher rate of intraoperative transfusions, and additional procedures were observed in patients that developed interstage RI. After stage 1, interstage RI patients had more major complications and higher interstage mortality (1% vs. 8%, p < 0.001). Furthermore, these patients developed more and severe complications after completion of stage 2. Mortality of patients with interstage RI was 38% vs. 8% without interstage RI. In 41% of patients with interstage RI, the renal function recovered before stage 2; however, the mortality after stage 2 remained 28% in those patients. Risk factors for the development of an interstage RI were age over 67 years, prolonged operative time, and additional procedure during stage 1., Conclusion: This study shows that interstage RI is a predictor for interstage and post-stage 2 morbidity and perioperative mortality. The causality of impaired renal function on outcome, however, remains unknown. Interstage RI may directly cause adverse outcome but may also be a surrogate marker for major complications.

Objective: The aim of this study was to establish clinically relevant outcome benchmark values using criteria for pancreatoduodenectomy (PD) with portomesenteric venous resection (PVR) from a low-risk cohort managed in high-volume centers., Summary Background Data: PD with PVR is regarded as the standard of care in patients with cancer involvement of the portomesenteric venous axis. There are, however, no benchmark outcome indicators for this population which hampers comparisons of patients undergoing PD with and without PVR resection., Methods: This multicenter study analyzed patients undergoing PD with any type of PVR in 23 high-volume centers from 2009 to 2018. Nineteen outcome benchmarks were established in low-risk patients, defined as the 75th percentile of the median outcome values of the centers (NCT04053998)., Results: Out of 1462 patients with PD and PVR, 840 (58%) formed the benchmark cohort, with a mean age was 64 (SD11) years, 413 (49%) were females. Benchmark cutoffs, among others, were calculated as follows: Clinically relevant pancreatic fistula rate (International Study Group of Pancreatic Surgery): ≤14%; in-hospital mortality rate: ≤4%; major complication rate Grade≥3 and the CCI up to 6 months postoperatively: ≤36% and ≤26, respectively; portal vein thrombosis rate: ≤14% and 5-year survival for patients with pancreatic ductal adenocarcinoma: ≥9%., Conclusion: These novel benchmark cutoffs targeting surgical performance, morbidity, mortality, and oncological parameters show relatively inferior results in patients undergoing vascular resection because of involvement of the portomesenteric venous axis. These benchmark values however can be used to conclusively assess the results of different centers or surgeons operating on this high-risk group.

Objectives: To analyze long-term oncological outcome along with prognostic risk factors in a large cohort of patients with colorectal liver metastases (CRLM) undergoing ALPPS., Background: ALPPS is a two-stage hepatectomy variant that increases resection rates and R0 resection rates in patients with primarily unresectable CRLM as evidenced in a recent randomized controlled trial. Long-term oncologic results, however, are lacking., Methods: Cases in- and outside the International ALPPS Registry were collected and completed by direct contacts to ALPPS centers to secure a comprehensive cohort. Overall, cancer-specific (CSS), and recurrence-free (RFS) survivals were analyzed along with independent risk factors using Cox-regression analysis., Results: The cohort included 510 patients from 22 ALPPS centers over a 10-year period. Ninety-day mortality was 4.9% and median overall survival, CSS, and RFS were 39, 42, and 15 months, respectively. The median follow-up time was 38 months (95% confidence interval 32-43 months). Multivariate analysis identified tumor-characteristics (primary T4, right colon), biological features (K/N-RAS status), and response to chemotherapy (Response Evaluation Criteria in Solid Tumors) as independent predictors of CSS. Traditional factors such as size of metastases, uni versus bilobar involvement, and liver-first approach were not predictive. When hepatic recurrences after ALPPS was amenable to surgical/ablative treatment, median CSS was significantly superior compared to chemotherapy alone (56 vs 30 months, P < 0.001)., Conclusions: This large cohort provides the first evidence that patients with primarily unresectable CRLM treated by ALPPS have not only low perioperative mortality, but achieve appealing long-term oncologic outcome especially those with favorable tumor biology and good response to chemotherapy.

Purpose: Almost 50% of patients diagnosed with colorectal cancer (CRC) will develop liver metastasis (LM). Although their only long-term curative treatment is surgery, less than half of these patients can be eventually resected. Therefore, palliative chemotherapy is offered as a definitive option, though with poor results. Recently, the University of Oslo group has published encouraging results in the treatment of these patients with liver transplantation (LT), whereby worldwide interest in this option has been renewed., Methods: A literature review of LT for patients with unresectable colorectal metastasis was performed. This included information regarding patient selection, complications, overall survival (OS) and disease-free survival (DFS), immunosuppression, chemotherapy, and description of the ongoing trials., Results: Improvements in OS and DFS have been observed in consecutive published prospective trials, as patient selection has been refined. Papers reporting OS of patients who randomly presented similar selection criteria also exhibited good results., Conclusion: LT within the available therapeutic options in patients with CRC-LM seems to be a compelling alternative in carefully selected patients. The ongoing trials will provide valuable information regarding selection criteria, immunosuppressive therapy and different modalities of adjuvant chemotherapy, which are, to our knowledge, the vital platform of LT in CRC-LM. Although some of the developing techniques involve living donors, graft availability for these patients remains a matter of major concern.

Background: Surgery is the most effective treatment option for neuroendocrine liver metastases (NELM). This study investigated the role of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) as a novel strategy in treatment of NELM., Methods: The International ALPPS Registry was reviewed to study patients who underwent ALPPS for NELM., Results: From 2010 to 2017, 954 ALPPS procedures from 135 international centers were recorded in the International ALPPS Registry. Of them, 24 (2.5%) were performed for NELM. Twenty-one patients entered the final analysis. Overall grade ≥3b morbidity was 9% after stage 1 and 27% after stage 2. Ninety-day mortality was 5%. R0 resection was achieved in 19 cases (90%) at stage 2. Median follow-up was 28 (19-48) months. Median disease free survival (DFS) was 17.3 (95% CI: 7.1-27.4) months, 1-year and 2-year DFS was 73.2% and 41.8%, respectively. Median overall survival (OS) was not reached. One-year and 2-year OS was 95.2% and 95.2%, respectively., Conclusions: ALPPS appears to be a suitable strategy for inclusion in the multimodal armamentarium of well-selected patients with neuroendocrine liver metastases. In light of the morbidity in this initial series and a high rate of disease-recurrence, the procedure should be taken with caution., (Copyright © 2019 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

The surgical strategy to resolve the underlying biliary pathology in patients with acute gallstone pancreatitis (AGP) remains controversial. The aim of this study was to evaluate the safety and effectiveness of early laparoscopic cholecystectomy (ELC) in patients with mild AGP. A retrospective cohort of consecutive patients diagnosed with mild AGP according to the Atlanta Guidelines from January 2009 to July 2019 was selected. Patients were assigned to surgery on the first available surgical shift, 48 h after the symptoms onset. Univariate analysis was performed to determine the association between AGP and grades of Balthazar (A, B and C) with time to surgery, days of hospitalization and postoperative complications. From 239 patients evaluated, 238 (99.58%) were operated by laparoscopic approach. Intraoperative cholangiogram was performed routinely. Choledocholithiasis, if present, was successfully treated by laparoscopic common bile duct exploration in all cases. A significant association was found between Balthazar grades and time to surgery (median of 3 days, p = 0.003), with length hospitalization and from surgery to discharge, with median of 4 days (p = 0.0001) and 2 days (p = 0.003), respectively. Mild postoperative complications (CD I/II) were observed in 22/239 patients (9.2%). This represents 2% of patients with grade A of Balthazar, 9% of grade B and 14% of grade C (p = 0.016). We observed no severe complications or mortality. ELC with routine intraoperative cholangiogram, performed on the first available surgical shift 48 h after the symptoms of pancreatitis onset, is a viable, effective and safe strategy for the resolution of mild AGP and its underlying biliary pathology in a single procedure.