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 vs. resistance to atezo+bev. We harnessed the power of single-cell RNA sequencing in advanced HCC to derive gene expression signatures recapitulating 21 cell phenotypes. These signatures were applied to 422 RNA-sequencing samples of patients with advanced HCC treated with atezo+bev (n = 317) vs. atezolizumab (n = 47) or sorafenib (n = 58) as comparators. We unveiled two distinct patterns of response to atezo+bev. First, an immune-mediated response characterised by the combined presence of CD8+ T effector cells and pro-inflammatory CXCL10+ macrophages, representing an immune-rich microenvironment. Second, a non-immune, angiogenesis-related response distinguishable by a reduced expression of the VEGF co-receptor neuropilin-1 (NRP1), a biomarker that specifically predicts improved OS upon atezo+bev vs. sorafenib (p = 0.039). Primary resistance was associated with an enrichment of immunosuppressive myeloid populations, namely CD14+ monocytes and TREM2+ macrophages, and Notch pathway activation. Based on these mechanistic insights we define "Immune-competent" and "Angiogenesis-driven" molecular subgroups, each associated with a significantly longer OS with atezo+bev vs. sorafenib (p of interaction = 0.027), and a "Resistant" subset. Our study unveils two distinct molecular subsets of clinical benefit to atezolizumab plus bevacizumab in advanced HCC ("Immune-competent" and "Angiogenesis-driven") as well as the main traits of primary resistance to this therapy, thus providing a molecular framework to stratify patients based on clinical outcome and guiding potential strategies to overcome resistance. Atezolizumab + bevacizumab (atezo+bev) is standard of care in advanced hepatocellular carcinoma (HCC), yet molecular determinants of clinical benefit to the combination remain unclear. This study harnesses the power of single-cell RNA sequencing, deriving gene expression signatures representing 21 cell subtypes in the advanced HCC microenvironment. By applying these signatures to RNA-sequencing samples, we reveal two distinct response patterns to atezo+bev and define molecular subgroups of patients ("Immune-competent" and "Angiogenesis-driven" vs. "Resistant") with differential clinical outcomes upon treatment with atezo+bev, pointing towards the role of immunosuppressive myeloid cell types and Notch pathway activation in primary resistance to atezo+bev. These results may help refine treatment strategies and improve outcomes for patients with advanced HCC, while also guiding future research aimed at overcoming resistance mechanisms.

Modern chemotherapy and repeat hepatectomy allow to tailor the surgical strategies for the treatment of colorectal liver metastases (CRLM). This study addresses the hypothesis that parenchymal-sparing hepatectomy reduces postoperative complications while ensuring similar oncologic outcomes compared to the standardized non-parenchymal-sparing procedures. Clinicopathological data of patients who underwent liver resection for CRLM between 2012 and 2019 at a hepatobiliary center in Switzerland were assessed. Patients were stratified according to the tumor burden score [TBS2 = (maximum tumor diameter in cm)2 + (number of lesions)2)] and were dichotomized in a lower and a higher tumor burden cohort according to the median TBS. Postoperative outcomes, overall survival (OS) and recurrence-free survival (RFS) of patients following parenchymal-sparing resection (PSR) for CRLM were compared with those of patients undergoing non-PSR. During the study period, 153 patients underwent liver resection for CRLM with curative intent. PSR was performed in 79 patients with TBS <4.5, and in 42 patients with TBS ≥4.5. Perioperative chemotherapy was administered in equal rates in both groups (PSR vs. non-PSR) both in TBS ≥4.5 and TBS <4.5. In patients with lower tumor burden (TBS <4.5), PSR was associated with lower overall complication rate (15.2% vs. 46.2%, p = 0.009), a trend for lower major complication rate (8.9% vs. 23.1%, p = 0.123), and shorter length of hospital stay (5 vs. 9 days, p = 0.006) in comparison to non-PSR. For TBS <4.5, PSR resulted in equivalent 5-year OS (48% vs. 39%, p = 0.479) and equivalent 5-year RFS rates (44% vs. 29%, p = 0.184) compared to non-PSR. For TBS ≥4.5, PSR resulted in lower postoperative complication rate (33.3% vs. 63.2%, p = 0.031), a trend for lower major complication rate (23.8% vs. 42.2%, p = 0.150), lower length of hospital stay (6 vs. 9 days, p = 0.005), equivalent 5-year OS (29% vs. 22%, p = 0.314), and equivalent 5-year RFS rates (29% vs. 18%, p = 0.156) compared to non-PSR. Among all patients treated with PSR, patients undergoing minimal-invasive hepatectomy had equivalent 5-year OS (42% vs. 37%, p = 0.261) and equivalent 5-year RFS (34% vs. 34%, p = 0.613) rates compared to patients undergoing open hepatectomy. PSR for CRLM is associated with lower postoperative morbidity, shorter length of hospital stay, and equivalent oncologic outcomes compared to non-PSR, independently of tumor burden. Our findings suggest that minimal-invasive PSR should be considered as the preferred method for the treatment of curatively resectable CRLM, if allowed by tumor size and location.

Alveolar echinococcosis (AE) in humans is caused by the larval (metacestode) stage of Echinococcus multilocularis, commonly known as the ‘fox tapeworm’. This disease predominantly targets the liver and has an invasive growth pattern, allowing it to spread to adjacent and distant tissues. Due to its gradual progression and tumour-like characteristics, early diagnosis and prompt intervention are crucial, particularly as there are currently no highly effective vaccines or chemotherapeutics against AE. Current estimates suggest that ~10,500 new infections occur annually worldwide; however, more research is required to refine the prevalence and incidence data for both human and animal hosts in endemic areas of the world. This article discusses the biology of E. multilocularis, outlines aspects of the pathogenesis, diagnosis, treatment, and management of AE, reviews its global distribution, annual incidence, and prevalence, highlights the role of molecular parasitology in advancing therapeutic strategies, and presents recommendations for improving the prevention and control of AE in human populations.

Inflammatory myofibroblastic tumor of the liver: A case report and review of literature