Prevalence, management and outcomes of pulmonary metastases in hepatocellular carcinoma: a systematic review and meta-analysis.

BACKGROUND: Hepatocellular carcinoma (HCC) presents a significant global health burden, with varying survival rates across regions. The presence of pulmonary metastases (PM) in HCC predicts a poorer prognosis, yet the global understanding of the progression and management is limited. METHODS: This study aims to systematically review the burden of PM in HCC, document current treatment approaches, and evaluate treatment effectiveness through meta-analysis. A comprehensive literature search was conducted across multiple databases. Articles were screened, and data extraction was performed independently by two reviewers. Statistical analyses were conducted to synthesise data and assess treatment outcomes. RESULTS: A total of 82 articles were included, comprising a population of 3241 participants with documented PM. Our analysis revealed a linear relationship between the HCC population size and the occurrence of PM (p < 0.005). Surgical intervention demonstrated the lowest hazard ratio (0.128) and significantly improved survival rates compared to other treatment modalities. However, data quality limitations underscore the need for further research to delineate patient subsets benefitting from surgical intervention for PM. CONCLUSION: Our findings advocate for continued investigation into PM management strategies, notably the role of surgical resection alongside systemic therapies, to improve outcomes in HCC patients with PM.

Entrustable Professional Activities in Postgraduate General Surgery Training: A Scoping Review.

OBJECTIVE: To provide an overview of the current use of Entrustable Professional Activities (EPAs) in postgraduate general surgery training internationally. BACKGROUND: Entrustable Professional Activities (EPAs) were introduced to connect clinical competencies and the professional activities to be entrusted to trainees on graduation. The popularity of EPAs as a framework for assessment is growing globally, including in general surgery. Anecdotally, there appears to be substantial variation in how they are implemented, yet a formal comparison of their use in postgraduate general surgery training is lacking. METHODS: A scoping review was performed, based on the original five-stage approach described by Arksey and O'Malley with the addition of protocol-specific items from the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols extension for scoping reviews (PRISMA-ScR). RESULTS: Twenty-nine published and grey literature sources were included in the review. Entrustable Professional Activity use in postgraduate general surgery training was identified in 11 unique contexts, including from North America, South America, Europe, Asia, Africa, and Australia. There were substantial differences in the scope and number of EPAs, tools used for EPA assessment, and how EPAs were sequenced through training. Despite wide variation, eight distinct EPAs were common to the majority (>80%) of countries. Several articles described findings of EPA use in postgraduate general surgery training, allowing identification of multiple barriers and facilitators to integration. CONCLUSIONS: This review provides guidance for certification and regulatory bodies, program directors, and institutions with ambitions to implement EPAs for assessment and curricular design. In settings where EPAs are already used, the data may facilitate refinement of programs and strategies.

Resection and reconstruction in high-grade pancreatic head injuries.

This study by Chui et al adds further important evidence in the treatment of high-grade pancreatic injuries and endorses the concept of the model of pancreatic trauma care designed to optimize treatment, minimize morbidity and enhance survival in patients with complex pancreatic injuries. Although the authors have demonstrated favorable outcomes based on their limited experience of 5 patients who underwent a pancreaticoduodenectomy (PD), including 2 patients who were "unstable" and did not have damage control surgery (DCS), we would caution against the general recommendations promoting index PD without DCS in "unstable" grade 5 pancreatic head injuries.

The role of national population-based registries in pancreatic cancer surgery research.

Research and innovation are critical for advancing the multidisciplinary management of pancreatic cancer. Registry-based studies (RBSs) are a complement to randomized clinical trials (RCTs). Compared with RCTs, RBSs offer cost-effectiveness, larger sample sizes, and representation of real-world clinical practice. National population-based registries (NPBRs) aim to cover the entire national population, and studies based on NPBRs are, compared to non-NPBRs, less prone to selection bias. The last decade has witnessed a dramatic increase in NPBRs in pancreatic cancer surgery, which has undoubtedly added invaluable knowledge to the body of evidence on pancreatic cancer management. However, several methodological shortcomings may compromise the quality of registry-based studies. These include a lack of control over data collection and a lack of reporting on the quality of the source registry or database in terms of validation of coverage and data completeness and accuracy. Furthermore, there is a significant risk of double publication from the most commonly used registries as well as the inclusion of historical data that is not relevant or representative of research questions addressing current practices.

Laparoscopic subtotal cholecystectomy outcomes across a low-and middle-income country metropolitan health service.

BACKGROUND: Laparoscopic subtotal cholecystectomy (LSC) is a safe alternative for difficult cholecystectomies to prevent bile duct injury and open conversion. The primary aim was to detail the use and outcomes on LSCs. METHODS: Retrospective analysis of a prospectively maintained database of laparoscopic cholecystectomy (LC). Relative clinical factors, outcomes, and 30-day follow-up between LSC and LC were compared using univariate and multivariate analyses. RESULTS: Six hundred and twenty four cholecystectomies were performed and 53 (8.5%) required LSC. 81.8% were fenestrating LSC. Male sex was significantly overrepresented in the LSC group (p < 0.01) and patients requiring LSC were significantly older (p < 0.01). Same admission cholecystectomy was associated with a higher risk of LSC (p < 0.01). Patients with a history of previous surgery, preoperative ERCP, or percutaneous cholecystostomy had an increased risk of undergoing LSC (p < 0.01). A necrotic gallbladder was the most significant predictor of the need for a LSC (p < 0.001). A contracted gallbladder, extensive adhesions, gallbladder empyema, and severe inflammation were significant predictors of difficulty (all p < 0.01). Postoperative complications occurred in 26.4% of LSC patients. There were ten (18.9%) Clavien-Dindo Grade III complications, 5.7% required ERCPs, and 9.4% required relook laparotomies. Significantly, more patients in the LSC group developed bile leaks (n = 8, 15%) (p < 0.001). There were two readmissions within 30 days, one mortality, and no BDIs occurred in the LSC cohort. CONCLUSION: LSC provides a feasible surgical option that should be utilized in complex cholecystitis.

Humoral immunoprofiling identifies novel biomarkers and an immune suppressive autoantibody phenotype at the site of disease in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a heterogeneous cancer, with minimal response to therapeutic intervention and with 85% of cases diagnosed at an advanced stage due to lack of early symptoms, highlighting the importance of understanding PDAC immunology in greater detail. Here, we applied an immunoproteomic approach to investigate autoantibody responses against cancer-testis and tumor-associated antigens in PDAC using a high-throughput multiplexed protein microarray platform, comparing humoral immune responses in serum and at the site of disease in order to shed new light on immune responses in the tumor microenvironment. We simultaneously quantified serum or tissue IgG and IgA antibody isotypes and subclasses in a cohort of PDAC, disease control and healthy patients, observing inter alia that subclass utilization in tumor tissue samples was predominantly immune suppressive IgG4 and inflammatory IgA2, contrasting with predominant IgG3 and IgA1 subclass utilization in matched sera and implying local autoantibody production at the site of disease in an immune-tolerant environment. By comparison, serum autoantibody subclass profiling for the disease controls identified IgG4, IgG1, and IgA1 as the abundant subclasses. Combinatorial analysis of serum autoantibody responses identified panels of candidate biomarkers. The top IgG panel included ACVR2B, GAGE1, LEMD1, MAGEB1 and PAGE1 (sensitivity, specificity and AUC values of 0.933, 0.767 and 0.906). Conversely, the top IgA panel included AURKA, GAGE1, MAGEA10, PLEKHA5 and XAGE3aV1 (sensitivity, specificity, and AUC values of 1.000, 0.800, and 0.954). Assessment of antigen-specific serum autoantibody glycoforms revealed abundant sialylation on IgA in PDAC, consistent with an immune suppressive IgA response to disease.

The management and outcomes of hepatocellular carcinoma in sub-Saharan Africa: a systematic review.

BACKGROUND: Hepatocellular carcinoma (HCC) is a leading cause of mortality in sub-Saharan Africa (SSA). This systematic review aimed to appraise all population-based studies describing the management and outcomes of HCC in SSA. METHODS: A systematic review based on a search in PubMed, PubMed Central, Scopus, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), AfricaWide and Cochrane up to June 2023 was performed. PRISMA guidelines for systematic reviews were followed. The study protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) (registration no: CRD42022363955). RESULTS: Thirty-nine publications from 15 of 48 SSA countries were identified; 3989 patients were studied. The majority (74%) were male, with median ages ranging from 28 to 54 years. Chronic Hepatitis B infection was a leading aetiology and non-cirrhotic HCC was frequently reported. Curative treatment (liver resection, transplantation and ablation) was offered to 6% of the cohort. Most patients (84%) received only best supportive care (BSC), with few survivors at one year. CONCLUSION: The majority of SSA countries do not have data reporting outcomes for HCC. Most patients receive only BSC, and curative treatment is seldom available in the region. Outcomes are poor compared to high-income countries.

Africa Guidelines for Hepatocellular Carcinoma Buildup Process.

PURPOSE: Hepatocellular carcinoma (HCC), the fourth most common cancer in Africa, has a dismal overall survival of only 3 months like in sub-Saharan Africa. This is affected by the low gross domestic product and human development index, absence of coherent guidelines, and other factors. METHODS: An open forum for HCC-experienced health care workers from Africa and the rest of the world was held in October 2021. Participants completed a survey to help assess the real-life access to screening, diagnoses, and treatment in the North and Southern Africa (NS), East and West Africa (EW), Central Africa (C), and the rest of the world. RESULTS: Of 461 participants from all relevant subspecialties, 372 were from Africa. Most African participants provided hepatitis B vaccination and treatment for hepatitis B and C. More than half of the participants use serum alpha-fetoprotein and ultrasound for surveillance. Only 20% reported using image-guided diagnostic liver biopsy. The Barcelona Clinic Liver Cancer is the most used staging system (52%). Liver transplant is available for only 28% of NS and 3% EW. C reported a significantly lower availability of resection. Availability of local therapy ranged from 94% in NS to 62% in C. Sorafenib is the most commonly used systemic therapy (66%). Only 12.9% reported access to other medications including immune checkpoint inhibitors. Besides 42% access to regorafenib in NS, second-line treatments were not provided. CONCLUSION: Similarities and differences in the care for patients with HCC in Africa are reported. This reconfirms the major gaps in access and availability especially in C and marginally less so in EW. This is a call for concerted multidisciplinary efforts to achieve and sustain a reduction in incidence and mortality from HCC in Africa.

Preoperative CA19.9 level predicts lymph node metastasis in resectable adenocarcinoma of the head of the pancreas: A further plea for biological resectability criteria.

INTRODUCTION: Lymph-nodal involvement (N+) represents an adverse prognostic factor after pancreatoduodenectomy (PD) for pancreatic adenocarcinoma (PDAC). Preoperative diagnostic and staging modalities lack sensitivity for identifying N+. This study aimed to investigate preoperative CA19.9 in predicting the N+ stage in resectable-PDAC (R-PDAC). METHODS: Patients included in a multi-institutional retrospective database of PDs performed for R-PDAC from January 2000 to June 2021 were analyzed. A preoperative laboratory value of CA19.9 >37 U/L was used in univariate and multivariate logistic regression analysis to determine a possible association with N+. Additionally, different cut-offs of CA19.9 related to the preoperative clinical T (cT) stage was assessed to evaluate the risk of N+. RESULTS: A total of 2034 PDs from thirteen centers were included in the study. CA19.9>37 U/L was significantly associated with higher N+ at univariate and multivariate analysis (P<0.001). CA19.9 levels >37 U/L were associated with N+ in 75.9%, 81.3%, and 85.7% of patients, respectively, in cT1, cT2, and cT3 tumors and with higher cut-off values for all cT stages. CONCLUSION: Lymph nodal involvement is strongly related to preoperative CA19.9 levels. Specially in patients staged as cT3 the CA 19.9 could represent a valid and easy tool to suspect nodal involvement. Due to these findings, R-PDAC patients with elevated CA19.9 values should be considered in a more biologically advanced stage.

The multi-societal European consensus on the terminology, diagnosis and management of patients with synchronous colorectal cancer and liver metastases: an E-AHPBA consensus in partnership with ESSO, ESCP, ESGAR, and CIRSE.

BACKGROUND: Contemporary management of patients with synchronous colorectal cancer and liver metastases is complex. The aim of this project was to provide a practical framework for care of patients with synchronous colorectal cancer and liver metastases with a focus on terminology, diagnosis and management. METHODS: This project was a multi-organisational, multidisciplinary consensus. The consensus group produced statements which focused on terminology, diagnosis and management. Statements were refined during an online Delphi process and those with 70% agreement or above were reviewed at a final meeting. Iterations of the report were shared by electronic mail to arrive at a final agreed document comprising twelve key statements. RESULTS: Synchronous liver metastases are those detected at the time of presentation of the primary tumour. The term "early metachronous metastases" applies to those absent at presentation but detected within 12 months of diagnosis of the primary tumour with "late metachronous metastases" applied to those detected after 12 months. Disappearing metastases applies to lesions which are no longer detectable on MR scan after systemic chemotherapy. Guidance was provided on the recommended composition of tumour boards and clinical assessment in emergency and elective settings. The consensus focused on treatment pathways including systemic chemotherapy, synchronous surgery and the staged approach with either colorectal or liver-directed surgery as first step. Management of pulmonary metastases and the role of minimally invasive surgery was discussed. CONCLUSIONS: The recommendations of this contemporary consensus provide information of practical value to clinicians managing patients with synchronous colorectal cancer and liver metastases.

Multisocietal European consensus on the terminology, diagnosis, and management of patients with synchronous colorectal cancer and liver metastases: an E-AHPBA consensus in partnership with ESSO, ESCP, ESGAR, and CIRSE.

BACKGROUND: Contemporary management of patients with synchronous colorectal cancer and liver metastases is complex. The aim of this project was to provide a practical framework for care of patients with synchronous colorectal cancer and liver metastases, with a focus on terminology, diagnosis, and management. METHODS: This project was a multiorganizational, multidisciplinary consensus. The consensus group produced statements which focused on terminology, diagnosis, and management. Statements were refined during an online Delphi process, and those with 70 per cent agreement or above were reviewed at a final meeting. Iterations of the report were shared by electronic mail to arrive at a final agreed document comprising 12 key statements. RESULTS: Synchronous liver metastases are those detected at the time of presentation of the primary tumour. The term 'early metachronous metastases' applies to those absent at presentation but detected within 12 months of diagnosis of the primary tumour, the term 'late metachronous metastases' applies to those detected after 12 months. 'Disappearing metastases' applies to lesions that are no longer detectable on MRI after systemic chemotherapy. Guidance was provided on the recommended composition of tumour boards, and clinical assessment in emergency and elective settings. The consensus focused on treatment pathways, including systemic chemotherapy, synchronous surgery, and the staged approach with either colorectal or liver-directed surgery as first step. Management of pulmonary metastases and the role of minimally invasive surgery was discussed. CONCLUSION: The recommendations of this contemporary consensus provide information of practical value to clinicians managing patients with synchronous colorectal cancer and liver metastases.

Novel CABIN score outperforms other prognostic models in predicting in-hospital mortality after salvage transjugular intrahepatic portosystemic shunting.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) is now established as the salvage procedure of choice in patients who have uncontrolled or severe recurrent variceal bleeding despite optimal medical and endoscopic treatment. AIM: To analysis compared the performance of eight risk scores to predict in-hospital mortality after salvage TIPS (sTIPS) placement in patients with uncontrolled variceal bleeding after failed medical treatment and endoscopic intervention. METHODS: Baseline risk scores for the Acute Physiology and Chronic Health Evaluation (APACHE) II, Bonn TIPS early mortality (BOTEM), Child-Pugh, Emory, FIPS, model for end-stage liver disease (MELD), MELD-Na, and a novel 5 category CABIN score incorporating Creatinine, Albumin, Bilirubin, INR and Na, were calculated before sTIPS. Concordance (C) statistics for predictive accuracy of in-hospital mortality of the eight scores were compared using area under the receiver operating characteristic curve (AUROC) analysis. RESULTS: Thirty-four patients (29 men, 5 women), median age 52 years (range 31-80) received sTIPS for uncontrolled (11) or refractory (23) bleeding between August 1991 and November 2020. Salvage TIPS controlled bleeding in 32 (94%) patients with recurrence in one. Ten (29%) patients died in hospital. All scoring systems had a significant association with in-hospital mortality (P < 0.05) on multivariate analysis. Based on in-hospital survival AUROC, the CABIN (0.967), APACHE II (0.948) and Emory (0.942) scores had the best capability predicting mortality compared to FIPS (0.892), BOTEM (0.877), MELD Na (0.865), Child-Pugh (0.802) and MELD (0.792). CONCLUSION: The novel CABIN score had the best prediction capability with statistical superiority over seven other risk scores. Despite sTIPS, hospital mortality remains high and can be predicted by CABIN category B or C or CABIN scores > 10. Survival was 100% in CABIN A patients while mortality was 75% for CABIN B, 87.5% for CABIN C, and 83% for CABIN scores > 10.

Entrustable professional activities in postgraduate general surgery training: a scoping review protocol.

INTRODUCTION: The competency-based medical education (CBME) movement continues to gain momentum in postgraduate physician training, resulting in increasing interest among surgical training programmes on how to implement it effectively. Entrustable professional activities (EPAs) were introduced to connect competencies (characteristics/abilities of learners) and the professional activities to be entrusted to them on qualification/graduation. Although reviews related to the field of general surgery have been published on specific aspects of CBME, for example, workplace-based assessment, there is a paucity of published guidance available for surgeon-educators to plan and implement CBME using an EPA framework. This scoping review aims to provide an overview of the current use of EPAs in general surgery. METHODS AND ANALYSIS: This scoping review will be based on the original five-stage approach described by Arksey and O'Malley with the addition of protocol-specific items from the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols extension for scoping reviews. The primary research question focuses on describing how EPAs have been used in general surgery and where potential gaps remain that warrant further study. The review will include peer-reviewed journal publications and an extensive review of grey literature sources. The following databases will be searched for published literature from 1 January 2005 to 31 December 2022: PubMed; CINAHL, Africa-Wide Information, PsycInfo and ERIC (via EBSCOhost); Scopus; and SciELO (via Web of Science). Studies that describe the use of EPAs for curriculum design, teaching and/or assessment of competence in postgraduate general surgery training will be eligible for inclusion. ETHICS AND DISSEMINATION: The institutional ethics board of the University of Cape Town has granted a waiver of formal approval requirement. The dissemination strategy includes publication of results in peer-reviewed journals, presentation at international conferences and presentation to relevant stakeholders as deemed appropriate.

Pro-MAP: a robust pipeline for the pre-processing of single channel protein microarray data.

BACKGROUND: The central role of proteins in diseases has made them increasingly attractive as therapeutic targets and indicators of cellular processes. Protein microarrays are emerging as an important means of characterising protein activity. Their accurate downstream analysis to produce biologically significant conclusions is largely dependent on proper pre-processing of extracted signal intensities. However, existing computational tools are not specifically tailored to the nature of these data and lack unanimity. RESULTS: Here, we present the single-channel Protein Microarray Analysis Pipeline, a tailored computational tool for analysis of single-channel protein microarrays enabling biomarker identification, implemented in R, and as an interactive web application. We compared four existing background correction and normalization methods as well as three array filtering techniques, applied to four real datasets with two microarray designs, extracted using two software programs. The normexp, cyclic loess, and array weighting methods were most effective for background correction, normalization, and filtering respectively. CONCLUSIONS: Thus, here we provided a versatile and effective pre-processing and differential analysis workflow for single-channel protein microarray data in form of an R script and web application ( https://metaomics.uct.ac.za/shinyapps/Pro-MAP/ .) for those not well versed in the R programming language.

Endoscopic versus percutaneous intervention for palliation in malignant hilar bile duct obstruction - A comparative cohort study.

BACKGROUND: Biliary drainage in patients managed palliatively for malignant hilar obstruction can be achieved by endoscopic transpapillary stenting using endoscopic retrograde cholangiography (ERC) or percutaneous transhepatic stent or catheter placement using percutaneous transhepatic cholangiography (PTC). This study compares ERC and PTC drainage for malignant hilar bile duct obstruction. METHODS: A retrospective study of drainage procedures at two academic hospitals was conducted from 2015 to 2020. Procedural success (divided into access-, bridging-, and technical success), therapeutic success, duration of therapeutic success and complications were analysed for different Bismuth-Corlette stricture types. RESULTS: A total of 293 patients were included, 153 (52.2%) in the ERC group and 140 (47.8%) in the PTC group. Access and bridging success in the ERC and PTC groups were 83.5% vs. 97.2% (p < 0.001) and 90.2% vs. 84.5% (p = 0.119), respectively. Technical and therapeutic success were equivalent between the two groups (98.3% vs. 99.3%, p = 0.854 and 81.7% vs. 73.3%, p = 0.242). Duration of therapeutic success was longer after ERC drainage compared to PTC drainage (p = 0.009) with a 3-month gain in duration of therapeutic success after ERC drainage (p = 0.006, 95% CI [26-160]). Cholangitis rates were equivalent (21.4% vs. 24.7%, p = 0.530), pancreatitis was more common in the ERC group (9.4% vs. 0%, p < 0.001) and procedure-related deaths more common in the PTC group (6.0% vs. 15.8%, p < 0.001). CONCLUSION: Although ERC and PTC drainage of malignant hilar obstruction were similar regarding technical and therapeutic success, ERC drainage was more durable. Outcome differences for B-C stricture types should be explored in future studies.

Multimodal perioperative assessment of liver function and volume in patients undergoing hepatectomy for colorectal liver metastasis: a comparison of the indocyanine green retention test, 99mTc mebrofenin hepatobiliary scintigraphy and gadoxetic acid enhanced MRI.

OBJECTIVES: To compare the dynamic changes in future liver remnant (FLR) function and volume after hepatectomy and to evaluate the associations between three modalities in assessment of liver function. METHODS: Liver function and volume were quantified pre-operatively, at post-operative day (POD) 7 and POD 28 in 10 patients with colorectal liver metastases undergoing hemihepatectomy using the indocyanine green retention (ICG) test, hepatobiliary scintigraphy (HBS) and gadoxetic acid-enhanced MRI. The 99mTc mebrofenin uptake rate in the FLR was applied as a reference of liver function. MRI-derived parameters including liver-to-muscle ratio (LMR), liver-to-spleen ratio (LSR) and hepatocellular uptake index (HUI) were used for liver function assessment. Spearman's correlation analysis was used to evaluate the associations. RESULTS: Increase in liver function ranged from 13 to 152% (median 92%) and in volume from 37 to 134% (median 79%). There was no significant discrepancy in increase between FLR function and volume during the first month following hepatectomy. LMR showed a significant correlation to ICG test (r = -0.66, p < 0.05) while LSR had an association with standardized FLR function obtained by HBS (r = -0.71, p < 0.05). During the first week after hepatectomy, pre-operative HUI and LMR showed the strongest correlation to the FLR growth in function and volume respectively (p < 0.05). CONCLUSION: The observed growth in FLR volume is closely related to the functional increase within 1 month after hepatectomy. Gadoxetic acid-enhanced MRI might substitute HBS for regional liver function assessment and provide an imaging tool for liver growth prediction. ADVANCES IN KNOWLEDGE: Liver function growth was parallel with liver volume increase during the perioperative period. Liver function assessment with gadoxetic acid-enhanced MRI was comparable with that of HBS indicating that gadoxetic acid-enhanced MRI could substitute HBS for regional liver function evaluation.

Molecular adsorbent recirculating system treatment in patients with post-hepatectomy liver failure: Long-term results of a pilot study.

BACKGROUND: Post-hepatectomy liver failure (PHLF) is the leading cause of postoperative mortality following major liver resection. Between December 2012 and May 2015, 10 consecutive patients with PHLF (according to the Balzan criteria) following major/extended hepatectomy were included in a prospective treatment study with the molecular adsorbent recirculating system (MARS). Sixty- and 90-day mortality rates were 0% and 10%, respectively. Of the nine survivors, four still had liver dysfunction at 90 days postoperatively. One-year overall survival (OS) of the MARS-PHLF cohort was 50%. The present study aims to assess long-term outcome of this cohort compared to a historical control cohort. METHODS: To compare long-term outcome of the MARS-PHLF treatment cohort with PHLF patients not treated with MARS, the present study includes all 655 patients who underwent major hepatectomy at Karolinska University Hospital between 2010 and 2018. Patients with PHLF were identified according to the Balzan criteria. RESULTS: The cohort was split into three time periods: pre-MARS period (n = 192), MARS study period (n = 207), and post-MARS period (n = 256). The 90-day mortality of patients with PHLF was 55% (6/11) in the pre-MARS period, 14% during the MARS study period (2/14), and 50% (3/6) in the post-MARS period (p = 0.084). Median OS (95% confidence interval (CI)) was 37.8 months (29.3-51.7) in the pre-MARS cohort, 57 months (40.7-75.6) in the MARS cohort, and 38.8 months (31.4-51.2) in the post-MARS cohort. The 5-year OS of 10 patients included in the MARS study was 40% and the median survival 11.6 months (95% CI: 3 to not releasable). In contrast, for the remaining 21 patients fulfilling the Balzan criteria during the study period but not treated with MARS, the 5-year OS and median survival were 9.5% and 7.3 months (95% CI, 0.5-25.9), respectively (p = 0.138)). CONCLUSIONS: MARS treatment may contribute to improved outcome of patients with PHLF. Further studies are needed.The initial pilot study was registered at ClinicalTrials.gov (NCT03011424).