Single-cell RNA seq-derived signatures define response patterns to atezolizumab + bevacizumab in advanced hepatocellular carcinoma.

Background & Aims: The combination of atezolizumab and bevacizumab (atezo+bev) is the current standard of care for advanced hepatocellular carcinoma (HCC), providing a median overall survival (OS) of 19.2 months. Here, we aim to uncover the underlying cellular processes driving clinical benefit versus resistance to atezo+bev.

[Cholangiocarcinomas].

The term cholangiocarcinoma (CCA) includes a group of malignant tumors that develop in the efferent bile ducts and are characterized by a high degree of heterogeneity. These differences between intrahepatic, perihilar and distal CCAs run through all aspects of the disease including the etiology, pathogenesis, symptoms, diagnostics and treatment. This review article presents the current developments in this field of diseases.

Integrating the new systemic treatment landscape and surgical therapy in hepatocellular carcinoma.

The treatment landscape of hepatocellular carcinoma has evolved rapidly within the last decade. Minimally-invasive techniques have reached a new level of safety, affording surgeons to pursue more aggressive treatment strategies to ultimately improve oncological outcomes. These procedures have been increasingly applied to treat patients with more progressed tumors and in select case even patients with advanced stage disease confined to the liver.

Short-term postoperative outcomes of lymphadenectomy for cholangiocarcinoma, hepatocellular carcinoma and colorectal liver metastases in the modern era of liver surgery: Insights from the StuDoQ|Liver registry.

Introduction: The clinical role of lymphadenectomy (LAD) as part of hepatic resection for malignancies of the liver remains unclear. In this study, we aimed to report on the use cases and postoperative outcomes of liver resection and simultaneous LAD for hepatic malignancies (HM).

Materials And Methods: Clinicopathological data from patients who underwent surgery at 13 German centers from 2017 to 2022 (n = 3456) was extracted from the StuDoQ|Liver registry of the German Society of General and Visceral Surgery.

Robotic versus laparoscopic versus open major hepatectomy - an analysis of costs and postoperative outcomes in a single-center setting.

Purpose: In the era of minimal-invasive surgery, the introduction of robotic liver surgery (RS) was accompanied by concerns about the increased financial expenses of the robotic technique in comparison to the established laparoscopic (LS) and conventional open surgery (OS). Therefore, we aimed to evaluate the cost-effectiveness of RS, LS and OS for major hepatectomies in this study.

Methods: We analyzed financial and clinical data on patients who underwent major liver resection for benign and malign lesions from 2017 to 2019 at our department.

Identification of IGF2 as Genomic Driver and Actionable Therapeutic Target in Hepatoblastoma.

Management of hepatoblastoma (HB), the most frequent pediatric liver cancer, is based on surgical resection and perioperative chemotherapy regimens. In this study, we aimed to identify actionable targets in HB and assess the efficacy of molecular therapies in preclinical models of HB. Paired tumor and adjacent tissues from 31 HBs and a validation set of 50 HBs were analyzed using RNA-seq, SNP, and methylation arrays.

Molecular Markers of Response to Anti-PD1 Therapy in Advanced Hepatocellular Carcinoma.

Background & Aims: Single-agent anti-PD1 checkpoint inhibitors convey outstanding clinical benefits in a small fraction (∼20%) of patients with advanced hepatocellular carcinoma (aHCC) but the molecular mechanisms determining response are unknown. To fill this gap, we herein analyze the molecular and immune traits of aHCC in patients treated with anti-PD1.

Methods: Overall, 111 tumor samples from patients with aHCC were obtained from 13 centers before systemic therapies.

Hepatocellular Carcinoma in Mongolia Delineates Unique Molecular Traits and a Mutational Signature Associated with Environmental Agents.

Purpose: Mongolia has the world's highest incidence of hepatocellular carcinoma (HCC), with ∼100 cases/100,000 inhabitants, although the reasons for this have not been thoroughly delineated.

Experimental Design: We performed a molecular characterization of Mongolian (n = 192) compared with Western (n = 187) HCCs by RNA sequencing and whole-exome sequencing to unveil distinct genomic and transcriptomic features associated with environmental factors in this population.

Results: Mongolian patients were younger, with higher female prevalence, and with predominantly HBV-HDV coinfection etiology.

Robotic Liver Surgery: Technical Advantages Over Laparoscopic Technique Based on Parameters of Surgical Complexity and Perioperative Outcomes.

In view of the limited availability, our study addresses the issue of optimal case selection for robotic liver surgery over standard laparoscopy offering an in-detail analysis of intra- and postoperative outcomes. Clinical and technical data of all consecutive cases of robotic liver surgery of a single high-volume center from 2018 to 2020 were collected prospectively. Second, we performed a retrospective analysis of all laparoscopic liver resections from 2015 to 2020.

Novel microenvironment-based classification of intrahepatic cholangiocarcinoma with therapeutic implications.

Objective: The diversity of the tumour microenvironment (TME) of intrahepatic cholangiocarcinoma (iCCA) has not been comprehensively assessed. We aimed to generate a novel molecular iCCA classifier that incorporates elements of the stroma, tumour and immune microenvironment ('STIM' classification).

Design: We applied virtual deconvolution to transcriptomic data from ~900 iCCAs, enabling us to devise a novel classification by selecting for the most relevant TME components.

CXCR2 inhibition enables NASH-HCC immunotherapy.

Objective: Hepatocellular carcinoma (HCC) is increasingly associated with non-alcoholic steatohepatitis (NASH). HCC immunotherapy offers great promise; however, recent data suggests NASH-HCC may be less sensitive to conventional immune checkpoint inhibition (ICI). We hypothesised that targeting neutrophils using a CXCR2 small molecule inhibitor may sensitise NASH-HCC to ICI therapy.

Inflamed and non-inflamed classes of HCC: a revised immunogenomic classification.

Objective: We previously reported a characterisation of the hepatocellular carcinoma (HCC) immune contexture and described an immune-specific class. We now aim to further delineate the immunogenomic classification of HCC to incorporate features that explain responses/resistance to immunotherapy.

Design: We performed RNA and whole-exome sequencing, T-cell receptor (TCR)-sequencing, multiplex immunofluorescence and immunohistochemistry in a novel cohort of 240 HCC patients and validated our results in other cohorts comprising 660 patients.

Complexity-Adjusted Learning Curves for Robotic and Laparoscopic Liver Resection: A Word of Caution.

Background: Minimally invasive liver surgery (MILS) has a high variance in the type of resection and complexity, which has been underestimated in learning curve studies in the past. The aim of this work was to evaluate complexity-adjusted learning curves over time for laparoscopic liver resection (LLR) and robotic liver resection (RLR).

Methods: Cumulative sum analysis (CUSUM) and complexity adjustment were performed using the Iwate score for LLR and RLR (n = 647).

Treatment of Intrahepatic Cholangiocarcinoma-A Multidisciplinary Approach.

Intrahepatic cholangiocarcinoma (iCC) is distinguished as an entity from perihilar and distal cholangiocarcinoma and gallbladder carcinoma. Recently, molecular profiling and histopathological features have allowed further classification. Due to the frequent delay in diagnosis, the prognosis for iCC remains poor despite major technical advances and multimodal therapeutic approaches.

Objective Response Predicts Survival in Advanced Hepatocellular Carcinoma Treated with Systemic Therapies.

Purpose: Because of the increased number of sequential treatments used for advanced hepatocellular carcinoma (HCC), there is a need for surrogate endpoints of overall survival (OS). We analyze whether objective response (OR) is an independent predictor and surrogate endpoint of OS.

Patients And Methods: A systematic review of randomized clinical trials (RCT) in advanced HCC published between 2010 and 2020 was conducted to explore OS surrogacy of OR by Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST (mRECIST).

Safety of intermittent Pringle maneuver during minimally invasive liver resection in patients with hepatocellular carcinoma with and without cirrhosis.

Purpose: The aim of this study was to analyze the impact of minimally invasive intermittent Pringle maneuver (IPM) on postoperative outcomes in patients with hepatocellular carcinoma (HCC) and liver cirrhosis.

Methods: In this retrospective cohort study, we evaluated the safety of IPM in patients with HCC who underwent minimally invasive liver resection during five years at our center. Factors influencing the use of IPM were examined in univariate and multivariate regression analysis.

Immunomodulatory Effects of Lenvatinib Plus Anti-Programmed Cell Death Protein 1 in Mice and Rationale for Patient Enrichment in Hepatocellular Carcinoma.

Background And Aims: Lenvatinib is an effective drug in advanced HCC. Its combination with the anti-PD1 (programmed cell death protein 1) immune checkpoint inhibitor, pembrolizumab, has generated encouraging results in phase Ib and is currently being tested in phase III trials. Here, we aimed to explore the molecular and immunomodulatory effects of lenvatinib alone or in combination with anti-PD1.

Evidence-Based Management of Hepatocellular Carcinoma: Systematic Review and Meta-analysis of Randomized Controlled Trials (2002-2020).

Background & Aims: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, with a rapidly changing landscape of treatments. In the past 20 years, numerous randomized controlled trials (RCTs) have aimed at improving outcomes across disease stages. We aimed to analyze the current evidence and identify potential factors influencing response to therapies.

Recurrence of Hepatocellular Carcinoma After Liver Transplantation is Associated with Episodes of Acute Rejections.

Purpose: The impact of acute rejection (AR) after liver transplantation (LT) for hepatocellular carcinoma (HCC) on patient outcome is uncertain. This aim of this study is to investigate whether AR is associated with HCC relapse and overall survival.

Patients And Methods: Patients undergoing LT for HCC between 2001 and 2015 were retrospectively analyzed with regard to histopathological proven AR within the median time until recurrence.

Cell of origin in biliary tract cancers and clinical implications.

Biliary tract cancers (BTCs) are aggressive epithelial malignancies that can arise at any point of the biliary tree. Albeit rare, their incidence and mortality rates have been rising steadily over the past 40 years, highlighting the need to improve current diagnostic and therapeutic strategies. BTCs show high inter- and intra-tumour heterogeneity both at the morphological and molecular level.

Predicting the Risk of Postoperative Complications in Patients Undergoing Minimally Invasive Resection of Primary Liver Tumors.

Minimal-invasive techniques are increasingly applied in clinical practice and have contributed towards improving postoperative outcomes. While comparing favorably with open surgery in terms of safety, the occurrence of severe complications remains a grave concern. To date, no objective predictive system has been established to guide clinicians in estimating complication risks as the relative contribution of general patient health, liver function and surgical parameters remain unclear.

Locoregional therapies in the era of molecular and immune treatments for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related mortality and has an increasing incidence worldwide. Locoregional therapies, defined as imaging-guided liver tumour-directed procedures, play a leading part in the management of 50-60% of HCCs. Radiofrequency is the mainstay for local ablation at early stages and transarterial chemoembolization (TACE) remains the standard treatment for intermediate-stage HCC.