Routine End-ischemic Hypothermic Oxygenated Machine Perfusion in Liver Transplantation From Donors After Brain Death: A Randomized Controlled Trial.

OBJECTIVE: To assess whether end-ischemic hypothermic oxygenated machine perfusion (HOPE) is superior to static cold storage (SCS) in preserving livers procured from donors after brain death (DBD). BACKGROUND: There is increasing evidence of the benefits of HOPE in liver transplantation, but predominantly in the setting of high-risk donors. METHODS: In this randomized clinical trial, livers procured from DBDs were randomly assigned to either end-ischemic dual HOPE for at least 2 hours or SCS (1:3 allocation ratio). The Model for Early Allograft Function (MEAF) was the primary outcome measure. The secondary outcome measure was 90-day morbidity (ClinicalTrials. gov, NCT04812054). RESULTS: Of the 104 liver transplantations included in the study, 26 were assigned to HOPE and 78 to SCS. Mean MEAF was 4.94 and 5.49 in the HOPE and SCS groups ( P =0.24), respectively, with the corresponding rates of MEAF >8 of 3.8% (1/26) and 15.4% (12/78; P =0.18). Median Comprehensive Complication Index was 20.9 after transplantations with HOPE and 21.8 after transplantations with SCS ( P =0.19). Transaminase activity, bilirubin concentration, and international normalized ratio were similar in both groups. In the case of donor risk index >1.70, HOPE was associated with significantly lower mean MEAF (4.92 vs 6.31; P =0.037) and lower median Comprehensive Complication Index (4.35 vs 22.6; P =0.050). No significant differences between HOPE and SCS were observed for lower donor risk index values. CONCLUSION: Routine use of HOPE in DBD liver transplantations does not seem justified as the clinical benefits are limited to high-risk donors.

Novel Benchmark Values for Open Major Anatomic Liver Resection in Non-cirrhotic Patients: A Multicentric Study of 44 International Expert Centers.

OBJECTIVE: This study aims at establishing benchmark values for best achievable outcomes following open major anatomic hepatectomy for liver tumors of all dignities. BACKGROUND: Outcomes after open major hepatectomies vary widely lacking reference values for comparisons among centers, indications, types of resections, and minimally invasive procedures. METHODS: A standard benchmark methodology was used covering consecutive patients, who underwent open major anatomic hepatectomy from 44 high-volume liver centers from 5 continents over a 5-year period (2016-2020). Benchmark cases were low-risk non-cirrhotic patients without significant comorbidities treated in high-volume centers (≥30 major liver resections/year). Benchmark values were set at the 75th percentile of median values of all centers. Minimum follow-up period was 1 year in each patient. RESULTS: Of 8044 patients, 2908 (36%) qualified as benchmark (low-risk) cases. Benchmark cutoffs for all indications include R0 resection ≥78%; liver failure (grade B/C) ≤10%; bile leak (grade B/C) ≤18%; complications ≥grade 3 and CCI ® ≤46% and ≤9 at 3 months, respectively. Benchmark values differed significantly between malignant and benign conditions so that reference values must be adjusted accordingly. Extended right hepatectomy (H1, 4-8 or H4-8) disclosed a higher cutoff for liver failure, while extended left (H1-5,8 or H2-5,8) were associated with higher cutoffs for bile leaks, but had superior oncologic outcomes, when compared to formal left hepatectomy (H1-4 or H2-4). The minimal follow-up for a conclusive outcome evaluation following open anatomic major resection must be 3 months. CONCLUSION: These new benchmark cutoffs for open major hepatectomy provide a powerful tool to convincingly evaluate other approaches including parenchymal-sparing procedures, laparoscopic/robotic approaches, and alternative treatments, such as ablation therapy, irradiation, or novel chemotherapy regimens.

Cholangiocarcinoma landscape in Europe: Diagnostic, prognostic and therapeutic insights from the ENSCCA Registry.

BACKGROUND & AIMS: Cholangiocarcinoma (CCA) is a rare and heterogeneous biliary cancer, whose incidence and related mortality is increasing. This study investigates the clinical course of CCA and subtypes (intrahepatic [iCCA], perihilar [pCCA], and distal [dCCA]) in a pan-European cohort. METHODS: The ENSCCA Registry is a multicenter observational study. Patients were included if they had a histologically proven diagnosis of CCA between 2010-2019. Demographic, histomorphological, biochemical, and clinical studies were performed. RESULTS: Overall, 2,234 patients were enrolled (male/female=1.29). iCCA (n = 1,243) was associated with overweight/obesity and chronic liver diseases involving cirrhosis and/or viral hepatitis; pCCA (n = 592) with primary sclerosing cholangitis; and dCCA (n = 399) with choledocholithiasis. At diagnosis, 42.2% of patients had local disease, 29.4% locally advanced disease (LAD), and 28.4% metastatic disease (MD). Serum CEA and CA19-9 showed low diagnostic sensitivity, but their concomitant elevation was associated with increased risk of presenting with LAD (odds ratio 2.16; 95% CI 1.43-3.27) or MD (odds ratio 5.88; 95% CI 3.69-9.25). Patients undergoing resection (50.3%) had the best outcomes, particularly with negative-resection margin (R0) (median overall survival [mOS] = 45.1 months); however, margin involvement (R1) (hazard ratio 1.92; 95% CI 1.53-2.41; mOS = 24.7 months) and lymph node invasion (hazard ratio 2.13; 95% CI 1.55-2.94; mOS = 23.3 months) compromised prognosis. Among patients with unresectable disease (49.6%), the mOS was 10.6 months for those receiving active palliative therapies, mostly chemotherapy (26.2%), and 4.0 months for those receiving best supportive care (20.6%). iCCAs were associated with worse outcomes than p/dCCAs. ECOG performance status, MD and CA19-9 were independent prognostic factors. CONCLUSION: CCA is frequently diagnosed at an advanced stage, a proportion of patients fail to receive cancer-specific therapies, and prognosis remains dismal. Identification of preventable risk factors and implementation of surveillance in high-risk populations are required to decrease cancer-related mortality. LAY SUMMARY: This is, to date, the largest international (pan-European: 26 hospitals and 11 countries) observational study, in which the course of cholangiocarcinoma has been investigated, comparing the 3 subtypes based on the latest International Classification of Diseases 11th Edition (ICD-11) (i.e., intrahepatic [2C12], perihilar [2C18], or distal [2C15] affected bile ducts), which come into effect in 2022. General and tumor-type specific features at diagnosis, risk factors, biomarker accuracy, as well as patient management and outcomes, are presented and compared, outlining the current clinical state of cholangiocarcinoma in Europe.

Early results of the implementation of laparoscopic major liver resection program.

BACKGROUND: Laparoscopic liver resections offer potential benefits but may require advanced laparoscopic skills and are volume dependent. METHODS: This retrospective study included 12 patients who underwent major laparoscopic resection and 24 patients after open major liver resection for liver malignancy in the time period between September 2020 and May 2021. The primary outcomes were complications according to Clavien-Dindo classification and duration of hospital stay. RESULTS: Median duration of hospital stay in laparoscopic resection group (6 days) was significantly shorter than in open resection group (8 days) (p = 0.046). Complications classified as grade II or higher were significantly less frequent in the laparoscopic resection group (2 patients) versus open resection group (13 patients) (p = 0.031). CONCLUSIONS: Although laparoscopic major liver resections should be limited to expert hepatobiliary centers and are characterized by long learning curve, this approach may offer favorable short-term outcomes even during launching a new program.

Synergistic effects of extracellular vesicle phenotyping and AFP in hepatobiliary cancer differentiation.

BACKGROUND: Biliary cancer, comprising cholangio- and gallbladder carcinomas, is associated with high mortality due to asymptomatic disease onset and resulting late diagnosis. Currently, no robust diagnostic biomarker is clinically available. Therefore, we explored the feasibility of extracellular vesicles (EVs) as a liquid biopsy tool for biliary cancer screening and hepatobiliary cancer differentiation. METHODS: Serum EVs of biliary cancer, hepatocellular carcinoma, colorectal cancer and non-small cell lung cancer patients, as well as from healthy individuals, were isolated by sequential two-step centrifugation and presence of indicated EVs was evaluated by fluorescence activated cell sorting (FACS) analysis. RESULTS: Two directly tumour-related antigen combinations (AnnV+ CD44v6+ and AnnV+ CD44v6+ CD133+ ) and two combinations related to progenitor cells from the tumour microenvironment (AnnV+ CD133+ gp38+ and AnnV+ EpCAM+ CD133+ gp38+ ) were associated with good diagnostic performances that could potentially be used for clinical assessment of biliary cancer and differentiation from other cancer entities. With 91% sensitivity and 69% specificity AnnV+ CD44v6+ EVs showed the most promising results for differentiating biliary cancers from HCC. Moreover using a combined approach of EV levels of the four populations with serum AFP values, we obtained a perfect separation of biliary cancer and HCC with sensitivity, specificity, positive and negative predictive value all reaching 100% respectively. CONCLUSIONS: EV phenotyping, especially if combined with serum AFP, represents a minimally invasive, accurate liquid biopsy tool that could improve cancer screening and differential diagnosis of hepatobiliary malignancies.

Laparoscopic Major Hepatectomy: Do Not Underestimate the Impact of Specimen Extraction Site.

BACKGROUND: In laparoscopic major hepatectomy, analysis of outcomes according to specimen extraction site remains poorly described. The aim was to compare postoperative outcomes according to specimen extraction site. METHODS: From 2000 to 2017, all laparoscopic major hepatectomies were reviewed and postoperative outcomes were analyzed according to specimen extraction site: subcostal (Group 1), midline (Group 2), or suprapubic (Group 3) incision. RESULTS: Among 163 patients, 15 (9.2%) belonged to Group 1, 49 (30.1%) in Group 2, and 99 (60.7%) in Group 3. The proportion of right-sided, left-sided, or central hepatectomies, mortality, and overall and severe complications were comparable between groups. Group 1 had larger tumors (61 vs. 38 vs. 47 mm; P = 0.014), higher operative time (338 vs. 282 vs. 260 min; P < 0.008), higher adjacent organ resection rate (46.6 vs. 16.3 vs. 7.1%; P < 0.001), and tended to increase pulmonary complications (40.0 vs. 12.2 vs. 18.2%; P = 0.064). In Group 2, a previous midline incision scar was more frequently used for specimen extraction site (65.3 vs. 26.6 and 30.3%, Group 1 and 3; P < 0.001). Postoperative incisional hernia was observed in 16.4% (n = 23) and was more frequent in Group 2 (26.6 vs. 6.6% and 10.1%, Group 1 and Group 3; P = 0.030). Finally, Group 2 (HR 2.63, 95% CI 1.41-3.53; P = 0.032) was the only independent predictive factor of postoperative incisional hernia. CONCLUSIONS: While using a previous incision makes sense, the increased risk of postoperative incisional hernia after midline incision promotes the suprapubic incision.

Hepatic abscess: a rare complication after liver transplant.

BACKGROUND: This study was conducted to evaluate the predisposing factors, microbiology, treatment, and outcomes associated with hepatic abscess, a rare but serious complication which may accur after an orthotopic liver transplant (OLT). METHODS: This was a retrospective study based on a prospectively maintained database of 1100 patients who underwent OLT at the Medical University of Warsaw. An abscess was defined on imaging as solitary or multiple localized parenchymal collections in patients with clinical signs of infection, with or without positive cultures from blood or abscess aspirate. RESULTS: Fifteen patients (1.4%) developed hepatic abscess, including 12 (80%) with multiple abscesses. Predisposing factors included biliary pathology (eight patients), hepaticojejunostomy (six patients), and hepatic artery stenosis or thrombosis (five patients). Ten patients were treated using multiple percutaneous and endoscopic interventional procedures in addition to antimicrobial treatment whereas five were treated solely with antibiotics. Five patients (33.3%) died due to multi-organ failure secondary to abscess treatment, including one unsuccessful case of re-OLT. Thirteen patients (87%) had bacterial growth and five (33.3%) had fungal growth in their blood or abscess aspirates. CONCLUSIONS: Hepatic abscess after liver transplantation may be treated successfully with percutaneous and endoscopic intervention, along with antibiotics according to the results of microbial cultures of blood and/or abscess aspirates.

Initial prevalence of anal human papilloma virus infection in liver transplant recipients.

Although liver transplant recipients are at increased risk of human papilloma virus (HPV)-related anal cancer, limited data are available regarding the initial prevalence of anal HPV infection in this population. Anal swabs collected from 50 liver transplant recipients within the first three postoperative weeks were subjected to real-time polymerase chain reaction for detection of the four HPV genotypes: 6, 11, 16, and 18. Predictors of any, low-risk, and high-risk anal HPV infection were evaluated. Overall, the prevalence of any anal HPV infection was 18.0%, with the corresponding rates for high- and low-risk HPV genotypes being 8.0% and 10.0%, respectively. Infection with any type of anal HPV was higher in patients with hepatitis B virus (HBV) infection (P = 0.027), ≥3 sexual partners (P = 0.031), and alcoholic liver disease (P = 0.063). HBV infection was the only factor significantly associated with high-risk HPV infection (P = 0.038). Male sex (P = 0.050), age ≥52 years (P = 0.016), ≥30 sexual partners (P = 0.003), age at first intercourse ≤18 years (P = 0.045), and time since first intercourse ≥38 years (P = 0.012) were identified as predictors of low-risk HPV infection. These results indicate that HPV vaccination of liver transplant candidates and screening for anal HPV infection in high-risk groups should be considered.

Combination of morphologic criteria and α-fetoprotein in selection of patients with hepatocellular carcinoma for liver transplantation minimizes the problem of posttransplant tumor recurrence.

BACKGROUND: Serum α-fetoprotein concentration (AFP) might be a useful addition to morphologic criteria for selecting patients with hepatocellular carcinoma (HCC) for liver transplantation (LT). The aim of this study was to evaluate the role of AFP in selecting HCC patients at minimal risk of posttransplant tumor recurrence in the setting of existing criteria. METHODS: This retrospective cohort study was based on 121 HCC patients after LT performed at a single institution. AFP was evaluated as a predictor of posttransplant tumor recurrence with respect to fulfillment of the Milan, University of California, San Francisco (UCSF), and Up-to-7 criteria. RESULTS: There was a nearly linear association between AFP and the risk of HCC recurrence (p < 0.001 for linear effect; p = 0.434 for nonlinear effect). AFP predicted HCC recurrence in patients (1) beyond the Milan criteria (p < 0.001; optimal cutoff 200 ng/ml); (2) within the UCSF criteria (p = 0.001; optimal cutoff 100 ng/ml) and beyond them (p = 0.015; optimal cutoff 200 ng/ml); and (3) within the Up-to-7 criteria (p = 0.001; optimal cutoff 100 ng/ml) and beyond them (p = 0.023; optimal cutoff 100 ng/ml) but not in patients within the Milan criteria (p = 0.834). Patients within either UCSF and Up-to-7 criteria with AFP level <100 ng/ml exhibited superior (100 %) 5-year recurrence-free survival-significantly higher than those within UCSF (p = 0.005) or Up-to-7 (p = 0.001) criteria with AFP levels higher than the estimated cutoffs or beyond with AFP levels less than the estimated cutoffs. CONCLUSIONS: Combining the UCSF and Up-to-7 criteria with an AFP level <100 ng/ml is associated with minimal risk of tumor recurrence. Hence, this combination might be useful for selecting HCC patients for LT.

Gut microbiota in cirrhotic liver transplant candidates.

BACKGROUND/AIMS: The purpose of this study was to evaluate the gut microflora of liver transplant candidates. METHODOLOGY: Fecal microflora of 20 cirrhotic liver transplant candidates was analyzed basing on prospectively collected stool samples. The results were compared with those of 20 non-cirrhotic patients with liver disease and/or abnormal liver function tests, 20 patients with Crohn's disease, and 20 patients without any gastrointestinal disease. Moreover, correlations between particular counts of microbiota, as well as between microbial counts and stool pH were examined. RESULTS: The pattern of fecal microbiota of liver transplant candidates was characterized by increased counts of lactobacilli (p=0.001), including hydrogen peroxide producing strains (p=0.008). In these patients, lactobacilli were positively correlated to enterococci (p=0.006) and bifidobacteria (p=0.004). No correlations other than those observed for lactobacilli in general were observed between hydrogen peroxide producing lactobacilli and the remaining microbiota. Increased yeast and Escherichia coli counts were associated with a tendency towards lower (p=0.095) and higher (p=0.072) stool pH, respectively. CONCLUSIONS: Surprisingly, gut microflora of liver transplant candidates with cirrhosis is particularly enriched with lactobacilli, including hydrogen peroxide producing strains. Thus, the use of other potentially beneficial microorganisms, such as particular yeast strains, might be more appropriate for these patients.

A novel radiomics approach for predicting TACE outcomes in hepatocellular carcinoma patients using deep learning for multi-organ segmentation.

Transarterial chemoembolization (TACE) represent the standard of therapy for non-operative hepatocellular carcinoma (HCC), while prediction of long term treatment outcomes is a complex and multifactorial task. In this study, we present a novel machine learning approach utilizing radiomics features from multiple organ volumes of interest (VOIs) to predict TACE outcomes for 252 HCC patients. Unlike conventional radiomics models requiring laborious manual segmentation limited to tumoral regions, our approach captures information comprehensively across various VOIs using a fully automated, pretrained deep learning model applied to pre-TACE CT images. Evaluation of radiomics random survival forest models against clinical ones using Cox proportional hazard demonstrated comparable performance in predicting overall survival. However, radiomics outperformed clinical models in predicting progression-free survival. Explainable analysis highlighted the significance of non-tumoral VOI features, with their cumulative importance superior to features from the largest liver tumor. The proposed approach overcomes the limitations of manual VOI segmentation, requires no radiologist input and highlight the clinical relevance of features beyond tumor regions. Our findings suggest the potential of this radiomics models in predicting TACE outcomes, with possible implications for other clinical scenarios.

Early adoption of laparoscopic liver surgery in Poland: a national retrospective cohort study.

BACKGROUND: The need for safe and efficient dissemination of minimally invasive approach in liver surgery is among the current challenges for hepatobiliary surgeons. After the stage of innovators and pioneers, the following countries should adopt a laparoscopic approach. The aim of this study was to assess the national experience and trend in implementing laparoscopic liver resection (LLR) in Poland. MATERIALS AND METHODS: A national registry of LLR performed in Poland was established in June 2020. All LLR cases performed before were included retrospectively, followed by prospectively collected new cases. Baseline characteristics, preoperative and intraoperative data, short-term results and long-term follow-up were recorded. RESULTS: Since 2010 up to the end of 2022 there were 718 LLRs performed in Poland. The national rate of laparoscopic approach has gradually increased since 2017 ( P <0.001), reaching the rate of 11.7% in 2022. There were 443 (61.7%), 107 (14.9%), and 168 (23.4%) LLRs performed in accordance to increasing grades of difficulty. The move towards more demanding cases had an increasing trend over the years ( P <0.001). Total intraoperative adverse event and postoperative severe complications rates were estimated for 13.5% ( n =97) and 6.7% ( n =48), respectively. 30-day reoperation, readmission and postoperative mortality rates were 3.6% ( n =26), 2.8% ( n =20), and 0.8% ( n =6), respectively. While the R0 resection margin was assessed in 643 (89.6%) cases, the total textbook outcomes (TO) were achieved in 525 (74.5%) cases. Overcoming the learning curve of 60 LLRs, resulted in an increasing TO rate from 72.3 to 80.6% ( P =0.024). CONCLUSIONS: It is the first national analysis of a laparoscopic approach in liver surgery in Poland. An increasing trend of minimizing invasiveness in liver resection has been observed. Responsible selection of cases in accordance with difficulty may provide results within global benchmark values and textbook outcomes already during the learning curve.

Early post-operative prediction of morbidity and mortality after a major liver resection for colorectal metastases.

BACKGROUND: An early prediction of poor outcomes is essential in the management of patients after a liver resection. The aim of this study was to evaluate the role of selected biochemical parameters on post-operative day 1 (POD 1) in the prediction of morbidity and mortality after a liver resection for colorectal metastases. METHOD: This retrospective study was based on 236 major liver resections for colorectal metastases performed between 2006 and 2011. Results of biochemical tests of blood samples obtained on POD 1 were assessed as predictors of primary outcome measures (hepatic and overall morbidity, 90-day mortality) using multiple regression and receiver-operating characteristics (ROC). RESULTS: Hepatic morbidity, overall morbidity and 90-day mortality rates were 18.6%, 28.0% and 4.7%, respectively. On the basis of multiple regression analysis and comparisons of the prediction models, serum bilirubin was selected for the prediction of hepatic (>2.05 mg/dl, sensitivity 69.2%, specificity 71.2%) and overall (>2.05 mg/dl, sensitivity 61.1% and specificity 71.2%) morbidity, and aspartate aminotransferase (AST) was selected for the prediction of 90-day mortality (>798 U/l, sensitivity 62.5% and specificity 90.4%). DISCUSSION: Biochemical analyses of blood on POD1 enables stratification of patients into low- and high-risk groups for negative outcomes, with serum bilirubin associated with overall and hepatic morbidity and AST associated with mortality.

Minimizing blood loss and transfusion rate in laparoscopic liver surgery: a review.

Laparoscopic liver resection has become a standard practice in many surgical wards in elective liver surgery, due to its positive impact on reducing hospital stay and postoperative complications, including lower blood loss and transfusion rate. However, achieving proper hemostasis in liver surgery, due to its vast blood supply, still remains a main concern to surgeons. Therefore, numerous techniques were and are still being developed to further reduce blood loss and transfusion rate. The aim of this literature review was to summarize the best available methods for achieving the minimal blood loss and transfusion rate in laparoscopic liver surgery, according to the newest data.

The Association of Polish Surgeons (APS) clinical guidelines for the use of laparoscopy in the management of abdominal emergencies. Part II.

Introduction: Over the past three decades, almost every type of abdominal surgery has been performed and refined using the laparoscopic technique. Surgeons are applying it for more procedures, which not so long ago were performed only in the classical way. The position of laparoscopic surgery is therefore well established, and in many operations it is currently the recommended and dominant method. Aim: The aim of the preparation of these guidelines was to concisely summarize the current knowledge on laparoscopy in acute abdominal diseases for the purposes of the continuous training of surgeons and to create a reference for opinions. Material and methods: The development of these recommendations is based on a review of the available literature from the PubMed, Medline, EMBASE and Cochrane Library databases from 1985 to 2022, with particular emphasis on systematic reviews and clinical recommendations of recognized scientific societies. The recommendations were formulated in a directive form and evaluated by a group of experts using the Delphi method. Results and conclusions: There are 63 recommendations divided into 12 sections: diagnostic laparoscopy, perforated ulcer, acute pancreatitis, incarcerated hernia, acute cholecystitis, acute appendicitis, acute mesenteric ischemia, abdominal trauma, bowel obstruction, diverticulitis, laparoscopy in pregnancy, and postoperative complications requiring emergency surgery. Each recommendation was supported by scientific evidence and supplemented with expert comments. The guidelines were created on the initiative of the Videosurgery Chapter of the Association of Polish Surgeons and are recommended by the national consultant in the field of general surgery. The second part of the guidelines covers sections 6 to12 and the following challenges for surgical practice: acute appendicitis, acute mesenteric ischemia, abdominal injuries, bowel obstruction, diverticulitis, laparoscopy in pregnancy and postoperative complications requiring a reoperation.

The Association of Polish Surgeons (APS) clinical guidelines for the use of laparoscopy in the management of abdominal emergencies. Part I.

Introduction: Over the past three decades, almost every type of abdominal surgery has been performed and refined using the laparoscopic technique. Surgeons are applying it for more procedures, which not so long ago were performed only in the classical way. The position of laparoscopic surgery is therefore well established, and in many operations it is currently the recommended and dominant method. Aim: The aim of the preparation of these guidelines was to concisely summarize the current knowledge on laparoscopy in acute abdominal diseases for the purposes of the continuous training of surgeons and to create a reference for opinions. Material and methods: The development of these recommendations is based on a review of the available literature from the PubMed, Medline, EMBASE and Cochrane Library databases from 1985 to 2022, with particular emphasis on systematic reviews and clinical recommendations of recognized scientific societies. Recommendations were formulated in a directive form and evaluated by a group of experts using the Delphi method. Results and conclusions: There are 63 recommendations divided into 12 sections: diagnostic laparoscopy, perforated ulcer, acute pancreatitis, incarcerated hernia, acute cholecystitis, acute appendicitis, acute mesenteric ischemia, abdominal trauma, bowel obstruction, diverticulitis, laparoscopy in pregnancy, and postoperative complications requiring emergency surgery. Each recommendation was supported by scientific evidence and supplemented with expert comments. The guidelines were created on the initiative of the Videosurgery Chapter of the Association of Polish Surgeons and are recommended by the national consultant in the field of general surgery. The first part of the guidelines covers 5 sections and the following challenges for surgical practice: diagnostic laparoscopy, perforated ulcer, acute pancreatitis, incarcerated hernia and acute cholecystitis. Contraindications for laparoscopy and the ERAS program are discussed.

Impact of Positive Lymph Nodes and Resection Margin Status on the Overall Survival of Patients with Resected Perihilar Cholangiocarcinoma: The ENSCCA Registry.

Background: Lymph node metastasis and positive resection margins have been reported to be major determinants of overall survival (OS) and poor recurrence-free survival (RFS) for patients who underwent resection for perihilar cholangiocarcinoma (pCCA). However, the prognostic value of positive lymph nodes independently from resection margin status on OS has not been evaluated. Methods: From the European Cholangiocarcinoma (ENSCCA) registry, patients who underwent resection for pCCA between 1994 and 2021 were included in this retrospective cohort study. The primary outcome was OS stratified for resection margin and lymph node status. The secondary outcome was recurrence-free survival. Results: A total of 325 patients from 11 different centers and six European countries were included. Of these, 194 (59.7%) patients had negative resection margins. In 113 (34.8%) patients, positive lymph nodes were found. Lymph node status, histological grade, and ECOG performance status were independent prognostic factors for survival. The median OS for N0R0, N0R1, N+R0, and N+R1 was 38, 30, 18, and 12 months, respectively (p < 0.001). Conclusion: These data indicate that in the presence of positive regional lymph nodes, resection margin status does not determine OS or RFS in patients with pCCA. Achieving negative margins in patients with positive nodes should not come at the expense of more extensive surgery and associated higher mortality.

Association between Time to Local Tumor Control and Treatment Outcomes Following Repeated Loco-Regional Treatment Session in Patients with Hepatocellular Carcinoma: A Retrospective, Single-Center Study.

BACKGROUND: Whether the number of loco-regional treatment sessions and the time required to obtain local tumor control (LTC) affects the prognosis of patients with hepatocellular carcinoma (HCC) remains controversial. This study aimed to determine whether a longer time to LTC is a significant and independent predictor of poor treatment outcomes. METHODS: In this retrospective study, we analyzed data of 139 treatment-naive patients with HCC who were not eligible for a treatment other than transarterial chemoembolization (TACE) at baseline. The outcome analyses were performed using the Cox proportional hazard model and Kaplan-Meier method, while the overall survival (OS) and progression free survival (PFS) were the primary study endpoints. RESULTS: Overall, LTC was achieved in 82 (59%) of patients, including 67 (81%) patients who achieved LTC following TACE sessions alone and 15 (19%) subjects required additional ablation session. The median OS did not differ significantly between groups that needed 2, 3, or >3 locoregional treatment sessions to achieve LTC (p = 0.37). Longer time to LTC (in weeks) was significantly associated with shorter OS in univariate analysis (p = 0.04), but not in an adjusted model (p = 0.14). Both univariate and adjusted analyses showed that longer time to reach LTC was significantly associated with shorter PFS (adjusted HR = 1.04, 95% CI 1.001-1.09, p = 0.048). CONCLUSIONS: These findings show that the longer time to LTC is not an independent predictor of OS, but suggest that PFS may be significantly shorter in patients with longer time to LTC.

Assessing the impact of COVID-19 on liver cancer management (CERO-19).

BACKGROUND & AIMS: The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems and it may have heavily impacted patients with liver cancer (LC). Herein, we evaluated whether the schedule of LC screening or procedures has been interrupted or delayed because of the COVID-19 pandemic. METHODS: An international survey evaluated the impact of the COVID-19 pandemic on clinical practice and clinical trials from March 2020 to June 2020, as the first phase of a multicentre, international, and observational project. The focus was on patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma, cared for around the world during the first COVID-19 pandemic wave. RESULTS: Ninety-one centres expressed interest to participate and 76 were included in the analysis, from Europe, South America, North America, Asia, and Africa (73.7%, 17.1%, 5.3%, 2.6%, and 1.3% per continent, respectively). Eighty-seven percent of the centres modified their clinical practice: 40.8% the diagnostic procedures, 80.9% the screening programme, 50% cancelled curative and/or palliative treatments for LC, and 41.7% modified the liver transplantation programme. Forty-five out of 69 (65.2%) centres in which clinical trials were running modified their treatments in that setting, but 58.1% were able to recruit new patients. The phone call service was modified in 51.4% of centres which had this service before the COVID-19 pandemic (n = 19/37). CONCLUSIONS: The first wave of the COVID-19 pandemic had a tremendous impact on the routine care of patients with liver cancer. Modifications in screening, diagnostic, and treatment algorithms may have significantly impaired the outcome of patients. Ongoing data collection and future analyses will report the benefits and disadvantages of the strategies implemented, aiding future decision-making. LAY SUMMARY: The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems globally. Herein, we assessed the impact of the first wave pandemic on patients with liver cancer and found that routine care for these patients has been majorly disrupted, which could have a significant impact on outcomes.

Does the difficulty grade of laparoscopic liver resection for colorectal liver metastases correlate with long-term outcomes?

INTRODUCTION: Prognosis of patients with colorectal liver metastases (CRLM) is strongly correlated with the oncological outcome after liver resection. The aim of this study was to analyze the impact of laparoscopic liver resection (LLR) difficulty score (IMM difficulty score) on the oncological results in patients treated for CRLM. METHODS: All patients who underwent LLRs for CRLM from 2000 to 2016 in our department, were retrospectively reviewed. Data regarding difficulty classification, -according to the Institute Mutualiste Montsouris score (IMM)-, recurrence rate, recurrence-free survival (RFS), overall survival (OS) and data regarding margin status were analyzed. RESULTS: A total of 520 patients were included. Patients were allocated into 3 groups based on IMM difficulty score of the LLR they underwent: there were 227 (43,6%), 84 (16,2%) and 209 (40,2%) patients in groups I, II and III, respectively. The R1 resection rate in group I, II and III were 8,8% (20/227), 11,9% (10/84) and 12,4% (26/209) respectively (p = 0.841). Three- and 5-year RFS rates were 77% and 73% in group I, 58% and 51% in group II, 61% and 53% in group III, respectively (p = 0.038). Three and 5-year OS rates were 87% and 80% for group I, 77% and 66% for group II, 80% and 69% for group III respectively (p = 0.022). CONCLUSION: The higher LLR difficulty score correlates with significant morbidity and worse RFS and OS, although the more technically demanding and difficult cases are not associated with increased rates of positive resection margins and recurrence.