Limitations of acetaminophen as a reference hepatotoxin for the evaluation of in vitro liver models.

Acetaminophen is commonly used as a reference hepatotoxin to demonstrate that in vitro human liver platforms can emulate features of clinical drug-induced liver injury. However, the induction of substantial cell death in these models typically requires acetaminophen concentrations (∼10 mM) far higher than blood concentrations of the drug associated with clinical hepatotoxicity (∼1 mM). Using the cytochrome P450 inhibitor 1-aminobenzotriazole, we show that acetaminophen toxicity in cultured human, mouse, and rat hepatocytes is not dependent on N-acetyl-p-benzoquinonimine formation, unlike the in vivo setting.

Pre-operative evaluation of spontaneous portosystemic shunts as a predictor of post-hepatectomy liver failure in patients undergoing liver resection for hepatocellular carcinoma.

Background: Post-hepatectomy liver failure (PHLF) can significantly compromise outcomes, especially in cirrhotic patients. The identification of accurate and non-invasive pre-operative predictors is of paramount importance to appropriately stratify patients according to their estimated risk and select the best treatment strategy.

Materials And Methods: Consecutive patients undergoing liver resection for HCC on cirrhosis between 1-2015 and 12-2020 at 10 international Institutions were enrolled and their pre-operative CT scans were evaluated for the presence of spontaneous portosystemic shunts (SPSS) to identify predictors of PHLF and develop a nomogram.

Safety of robotic cholecystectomy as index training procedure: the UK experience.

Aims: To evaluate the safety profile of robotic cholecystectomy performed within the United Kingdom (UK) Robotic Hepatopancreatobiliary (HPB) training programme.

Methods: A retrospective evaluation of prospectively collected data from eleven centres participating in the UK Robotic HPB training programme was conducted. All adult patients undergoing robotic cholecystectomy for symptomatic gallstone disease or gallbladder polyp were considered.

Biliary tract cancer.

Background: Biliary tract cancers comprise a heterogeneous collection of malignancies usually described as cholangiocarcinoma of the intra- or extrahepatic bile duct, including perihilar cholangiocarcinoma and gallbladder cancer.

Methods: A review of pertinent parts of the ESSO core curriculum for the UEMS diploma targets (Fellowships exam, EBSQ), based on updated and available guidelines for diagnosis, surgical treatment and oncological management of cholangiocarcinoma.

Results: Following the outline from the ESSO core curriculum we present the epidemiology and risk factors for cholangiocarcinoma, as well as the rationale for the current diagnosis, staging, (neo-)adjuvant treatment, surgical management, and short- and long-term outcomes.

Hepatocellular carcinoma.

An update on the management of Hepatocellular carcinoma (HCC) is provided in the present article for those interested in the UEMS/EBSQ exam in Surgical Oncology. The most recent publications in HCC, including surveillance, guidelines, and indications for liver resection, liver transplantation, and locoregional or systemic therapies, are summarised. The objective is to yield a set of main points regarding HCC that are required in the core curriculum of hepatobiliary oncological surgery.

E-AHPBA-ESSO-ESSR Innsbruck consensus guidelines for preoperative liver function assessment before hepatectomy.

Background: Posthepatectomy liver failure (PHLF) contributes significantly to morbidity and mortality after liver surgery. Standardized assessment of preoperative liver function is crucial to identify patients at risk. These European consensus guidelines provide guidance for preoperative patient assessment.

Genomic profiling of idiopathic peri-hilar cholangiocarcinoma reveals new targets and mutational pathways.

Peri-hilar cholangiocarcinoma (pCCA) is chemorefractory and limited genomic analyses have been undertaken in Western idiopathic disease. We undertook comprehensive genomic analyses of a U.K.

Long-term morbidity after surgery for perihilar cholangiocarcinoma: A cohort study.

Background: Surgery for perihilar cholangiocarcinoma (pCCA) offers the only possibility of long-term survival, but remains a formidable undertaking. Traditionally, 90-day post-operative complications and death are used to define operative risk. However, there is concern that this metric may not accurately capture long-term morbidity after such complex surgery.

Incidence and risk factors for anastomotic bile leakage in hepatic resection with bilioenteric reconstruction - A international multicenter study.

Background: Anastomotic leak (AL) after bilioenteric reconstruction (BR) is a feared complication after bile duct resection, especially in combination with liver resection. Literature on surgical outcome is sparse. This study aimed to determine the incidence and risk factors for AL after combined liver and bile duct resection with a focus on operative or endoscopic reinterventions.

Primary Tumor Resection is Associated with Improved Disease-Specific Mortality in Patients with Stage IV Small Intestinal Neuroendocrine Tumors (NETs): A Comparison of Upfront Surgical Resection Versus a Watch and Wait Strategy in Two Specialist NET Centers.

Introduction: Small intestinal neuroendocrine tumors (SI-NETs) often present with metastatic disease. An ongoing debate exists on whether to perform primary tumor resection (PTR) in patients with stage IV SI-NETs, without symptoms of the primary tumor and inoperable metastatic disease.

Objective: The aim of this study was to compare a treatment strategy of upfront surgical resection versus a surveillance strategy of watch and wait.

Laparoscopic versus open resections in the posterosuperior liver segments within an enhanced recovery programme (ORANGE Segments): study protocol for a multicentre randomised controlled trial.

Background: A shift towards parenchymal-sparing liver resections in open and laparoscopic surgery emerged in the last few years. Laparoscopic liver resection is technically feasible and safe, and consensus guidelines acknowledge the laparoscopic approach in the posterosuperior segments. Lesions situated in these segments are considered the most challenging for the laparoscopic approach.

Surgical management of suspected gallbladder cancer: The role of intraoperative frozen section for diagnostic confirmation.

Background: Preoperative diagnosis for suspected gallbladder cancers is challenging, with a risk of overtreating benign disease, for example, xanthogranulomatous cholecystitis, with radical cholecystectomies. We retrospectively evaluated the surgeon's intraoperative assessment alone, and with the addition of intraoperative frozen sections, for suspected gallbladder cancers from a tertiary hepatobiliary multidisciplinary team (MDT).

Methods: MDT patients with complex gallbladder disease were included.

Appendiceal goblet cell carcinomas have poor survival despite completion surgery.

Purpose: Appendiceal goblet cell carcinomas (aGCCs) are rare but aggressive tumours associated with significant mortality. We retrospectively reviewed the outcomes of aGCC patients treated at our tertiary referral centre.

Methods: We analysed aGCC patients, diagnosed between 1990-2016, assessing the impact of completion surgery and tumour factors on survival.

Robotic Surgery for Malignant Liver Disease: a Systematic Review of Oncological and Surgical Outcomes.

Robot-assisted laparoscopic surgery is yet another modification of minimally invasive liver surgery. It is described as feasible and safe from the surgical point of view; however, oncological outcomes need to be adequately analysed to justify the use of this technique when resecting malignant liver tumours. We reviewed existing English medical literature on robot-assisted laparoscopic liver surgery.

The impact of lymph node metastases and right hemicolectomy on outcomes in appendiceal neuroendocrine tumours (aNETs).

Introduction: European Neuroendocrine Tumour Society (ENETS) recommends managing appendiceal neuroendocrine tumours (aNET) with appendicectomy and possibly completion right hemicolectomy (CRH). However, disease behaviour and survival patterns remain uncertain.

Materials And Methods: We retrospectively assessed the impact of lymph nodes and CRH on outcomes, including survival, in all aNET patients diagnosed between 1990 and 2016.

Prognosis and Circumferential Margin in Patients with Resected Hilar Cholangiocarcinoma.

Background: Resection margin status is a known prognosticator in patients who undergo resection for hilar cholangiocarcinoma. However, the influence of an isolated positive circumferential margin on clinical outcome is unclear.

Methods: Patients with resected de novo hilar cholangiocarcinoma from two European hepatobiliary centres (Medical University of Vienna and Aintree University Hospital, 2006-2016) were classified according to resection margin status (negative, surgically positive, isolated circumferentially positive) and investigated with respect to overall survival (OS), recurrence-free survival (RFS) and recurrence pattern.

A simple scoring model for predicting early graft failure and postoperative mortality after liver transplantation.

Introduction And Objectives: Graft failure and postoperative mortality are the most serious complications after liver transplantation. The aim of this study is to establish a prognostic scoring system to predict graft and patient survival based on serum transaminases levels that are routinely used during the postoperative period in human cadaveric liver transplants.

Patients And Methods: Postoperative graft failure and patient mortality after liver transplant were analyzed from a consecutive series of 1299 patients undergoing cadaveric liver transplantation.

Exosomal Transport of Hepatocyte-Derived Drug-Modified Proteins to the Immune System.

Idiosyncratic drug-induced liver injury (DILI) is a rare, often difficult-to-predict adverse reaction with complex pathomechanisms. However, it is now evident that certain forms of DILI are immune-mediated and may involve the activation of drug-specific T cells. Exosomes are cell-derived vesicles that carry RNA, lipids, and protein cargo from their cell of origin to distant cells, and they may play a role in immune activation.

Recipient body mass index and infectious complications following liver transplantation.

Background: Nutritional problems are common in patients requiring liver transplantation. Recipient obesity or malnutrition are thought to increase postoperative complications. Body mass index (BMI) is commonly used prior to major surgery but its value specifically in liver transplant assessment has not been established.

Preoperative Leucocyte-Based Inflammatory Scores in Patients with Colorectal Liver Metastases: Can We Count on Them?

Background: Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR) have been identified as potential prognostic factors for overall survival (OS) in primary colorectal cancer, and there is a growing interest in their use in colorectal liver metastases (CLMs). However, optimal cut-off values for these ratios have not been defined by making comparison between series difficult. This study aimed to confirm the prognostic value of inflammatory scores in patients undergoing resection for CLM.

Clinical outcome after resection of early-stage hilar cholangiocarcinoma.

Background: Liver transplantation in patients with unresectable early-stage (<3 cm, node negative) hilar cholangiocarcinoma has been recently reported to be associated with longer survival compared to liver resection and therefore suggested as potential treatment option also in resectable disease. Here, we investigated the outcome of resection in early-stage tumours as the standard of care in an experienced European centre.

Methods: Patients with de novo resectable hilar cholangiocarcinomas who underwent liver resection between mid-2009 and December 2017 were classified as early-stage (<3 cm and node negative) or later-stage tumours (≥3 cm and/or node positive), and were investigated with respect to clinical outcome.

Validation of clinical prognostic scores for patients treated with curative-intent for recurrent colorectal liver metastases.

Background: Scoring systems were developed to stratify patients with colorectal liver metastases considered for liver resection into different risk groups. Such scores have never been evaluated in recurrent liver metastases. The aim of this study was to evaluate whether these scores are applicable to patients with recurrent colorectal liver metastases and treated with curative intent.

Influence of the primary tumour location in patients undergoing surgery for colorectal liver metastases.

Background: The prognosis of patients undergoing liver resection for colorectal liver metastases (CLM) seems to be altered when the primary tumour is right-sided. However, data are lacking and conflicting. We aimed to evaluate the influence of the primary tumour location on oncologic outcomes following such surgery.