Does minimally invasive liver resection improve long-term survival compared to open resection for hepatocellular carcinoma? A systematic review and meta-analysis

Introduction: Minimally invasive liver surgery for hepatocellular carcinoma has gained widespread interest as an alternative to conventional open liver surgery. However, long-term survival benefits of this approach seem unclear. This meta-analysis was conducted to investigate long-term survival following minimally invasive liver surgery.Method: A systematic review was performed to identify studies comparing long-term survival after minimally invasive liver surgery and open liver surgery until January 2020. The I2 test was used to test for statistical heterogeneity and publication bias was assessed using Egger test. Random-effects meta-analysis was performed for all-cause 5-year (main outcome) and 3-year mortality, and disease-specific 5-year and 3-year mortality. Meta-regression was performed for the 5-year and 3-year survival outcomes with adjustment for study factors (region, design), annual center volume, patient factors (American Society of Anesthesiologists (ASA) grade, gender, age, body mass index, cirrhosis, tumor size, and number), and resection extent. Sensitivity analyses were performed on studies by study year, region, annual center volume, and resection type.Result: The review identified 50 relevant studies including 13,731 patients undergoing liver resection for hepatocellular carcinoma of which 4071 (25.8%) underwent minimally invasive liver surgery. Pooled analysis revealed similar all-cause (odds ratio: 0.83, 95% confidence interval: 0.70–1.11, p = 0.3) and disease-specific (odds ratio: 0.93, 95% confidence interval: 0.80–1.09, p = 0.4) 5-year mortality after minimally invasive liver surgery compared with open liver surgery. Sensitivity analysis of published studies from 2010 to 2019 demonstrated a significantly lower disease-specific 3-year mortality (odds ratio: 0.75, 95% confidence interval: 0.59–0.96, p = 0.022) and all-cause 5-year mortality (odds ratio: 0.63, 95% confidence interval: 0.50–0.81, p = 0.002). Meta-regression identified no confounding factors in all analyses.Conclusions: Improvement in minimally invasive liver surgery techniques over the past decade appears to demonstrate superior disease-specific mortality with minimally invasive liver surgery compared to open liver surgery. Therefore, minimally invasive liver surgery can be recommended as an alternative surgical approach for hepatocellular carcinoma

The impact of time to death in donors after circulatory death on recipient outcome in simultaneous pancreas-kidney transplantation

Time to arrest in donors after circulatory death is unpredictable and can vary. This leads to variable periods of warm ischaemic damage prior to pancreas transplantation. There is little evidence supporting procurement team stand-down times based on donor time to death (TTD). We examined what impact TTD had on pancreas graft outcomes following DCD SPK transplantation. Data were extracted from the UK transplant registry from 2014 to 2022. Predictors of graft loss were evaluated by a Cox proportional hazards model. Adjusted restricted cubic spline (RCS) models were generated to further delineate the relationship between TTD and outcome. Three-hundred-and-seventy-five DCD simultaneous kidney-pancreas transplant recipients were included. Increasing TTD was not associated with graft survival (aHR 0.98, 95% CI 0.68-1.41, P=0.901). Increasing asystolic time worsened graft survival (aHR 2.51, 95% CI 1.16-5.43, P=0.020). RCS modelling revealed a non-linear relationship was demonstrated between asystolic time and graft survival, and no relationship between TTD and graft survival. We found no evidence that TTD impacts on pancreas graft survival after DCD SPK transplantation, however increasing asystolic time was a significant predictor of graft loss. Procurement teams should attempt to minimise asystolic time to optimize pancreas graft survival rather than focus on the duration of TTD

British Society of Gastroenterology guidelines for the diagnosis and management of cholangiocarcinoma

These guidelines for the diagnosis and management of cholangiocarcinoma (CCA) were commissioned by the British Society of Gastroenterology liver section. The guideline writing committee included a multidisciplinary team of experts from various specialties involved in the management of CCA, as well as patient/public representatives from AMMF (the Cholangiocarcinoma Charity) and PSC Support. Quality of evidence is presented using the Appraisal of Guidelines for Research and Evaluation (AGREE II) format. The recommendations arising are to be used as guidance rather than as a strict protocol-based reference, as the management of patients with CCA is often complex and always requires individual patient-centred considerations

AFP, PIVKAII, GP3, SCCA-1 and follisatin as surveillance biomarkers for hepatocellular cancer in non-alcoholic and alcoholic fatty liver disease

<p>Abstract</p> <p>Background</p> <p>The incidence and mortality of hepatocellular cancer (HCC) complicating alcoholic and non-alcoholic fatty liver diseases (ALD and NAFLD) is rising in western societies. Despite knowing the at risk populations for HCC development, the lack of sensitive and specific means of surveillance hampers disease detection at curable stages. The most widely used serum HCC marker is alpha-fetoprotein (AFP), while PIVKA-II, glypican-3 (GP3) and Squamous Cell Carcinoma Antigen -1 (SCCA-1) have been proposed as new biomarkers. Assessment of these HCC biomarkers has largely been performed in patients with viral hepatitis. We conducted a cross sectional study assessing the value of these serum proteins, as well a novel candidate biomarker -follistatin – in patients with HCC arising on a background of ALD or NAFLD.</p> <p>Methods</p> <p>Pre-treatment serum samples from 50 patients with HCC arising on a background of ALD (n = 31) or NAFLD (n = 19) were assessed by specific ELISA assay for PIVKAII, Glypican-3, SCCA-1 and Follistatin. Results were compared and contrasted with a control patient group with biopsy proven steatohepatitis-related cirrhosis (n = 41). The diagnostic accuracy of each of the candidate biomarkers was evaluated using receiver operating characteristic (ROC) curve analysis, reporting the area under the curve (AUC) and its 95% confidence interval (CI). Performance was compared to that of the established biomarker, AFP.</p> <p>Results</p> <p>Serum levels of all proteins were assessed by specific ELISA assays. GP3, SCCA-1 and follistatin had no HCC surveillance benefit in these patients. AFP and PIVKAII were superior to the other markers, particularly in combination.</p> <p>Conclusion</p> <p>We conclude that while novel means of surveillance are urgently required, the combination of AFP and PIVKAII for HCC is an improvement on AFP alone in ALD/NAFLD patients. Furthermore, our data in this homogenous subset of patients- particularly that confirming no role for SCCA-1 – suggests that the choice of optimal biomarkers for HCC surveillance may be determined by the aetiology of underlying chronic liver disease.</p

Type of calcineurin inhibitor and long-term outcomes following liver transplantation in patients with primary biliary cholangitis – an ELTR study

Background &amp; Aims: Tacrolimus has been associated with recurrence of primary biliary cholangitis (PBC) after liver transplantation (LT), which in turn may reduce survival. This study aimed to assess the association between the type of calcineurin inhibitor used and long-term outcomes following LT in patients with PBC. Methods: Survival analyses were used to assess the association between immunosuppressive drugs and graft or patient survival among adult patients with PBC in the European Liver Transplant Registry. Patients who received a donation after brain death graft between 1990 and 2021 with at least 1 year of event-free follow-up were included. Results: In total, 3,175 patients with PBC were followed for a median duration of 11.4 years (IQR 5.9–17.9) after LT. Tacrolimus (Tac) was registered in 2,056 (64.8%) and cyclosporin in 819 (25.8%) patients. Following adjustment for recipient age, recipient sex, donor age, and year of LT, Tac was not associated with higher risk of graft loss (adjusted hazard ratio [aHR] 1.07, 95% CI 0.92-1.25, p = 0.402) or death (aHR 1.06, 95% CI 0.90-1.24, p = 0.473) over cyclosporin. In this model, maintenance mycophenolate mofetil (MMF) was associated with a lower risk of graft loss (aHR 0.72, 95% CI 0.60-0.87, p &lt;0.001) or death (aHR 0.72, 95% CI 0.59-0.87, p &lt;0.001), while these risks were higher with use of steroids (aHR 1.31, 95% CI 1.13-1.52, p &lt;0.001, and aHR 1.34, 95% CI 1.15-1.56, p &lt;0.001, respectively). Conclusions: In this large LT registry, type of calcineurin inhibitor was not associated with long-term graft or recipient survival, providing reassurance regarding the use of Tac post LT in the population with PBC. Patients using MMF had a lower risk of graft loss and death, indicating that the threshold for combination treatment with Tac and MMF should be low. Impact and implications: This study investigated the association between immunosuppressive drugs and the long-term survival of patients with primary biliary cholangitis (PBC) following donation after brain death liver transplantation. While tacrolimus has previously been related to a higher risk of PBC recurrence, the type of calcineurin inhibitor was not related to graft or patient survival among patients transplanted for PBC in the European Liver Transplant Registry. Additionally, maintenance use of mycophenolate was linked to lower risks of graft loss and death, while these risks were higher with maintenance use of steroids. Our findings should provide reassurance for physicians regarding the continued use of Tac after liver transplantation in the population with PBC, and suggest potential benefit from combination therapy with mycophenolate.</p

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio