Viral Hepatitis in Western Patients with Advanced Intrahepatic Cholangiocarcinoma: Retrospective Assessment of Prevalence, Prognostic and Predictive Significance.

Despite a biologically established causative role of viral hepatitis (VH), i.e. HBV and HCV infections, on intrahepatic cholangiocarcinoma (ICC), only few large Western cohorts exploring the association between VH and ICC development are available.

Intestinal Microbiota Increases Cell Proliferation of Colonic Mucosa in Human-Flora-Associated (HFA) Mice.

Intestinal epithelium renewal strictly depends on fine regulation between cell proliferation, differentiation, and apoptosis. While murine intestinal microbiota has been shown to modify some epithelial cell kinetics parameters, less is known about the role of the human intestinal microbiota. Here, we investigated the rate of intestinal cell proliferation in C3H/HeN germ-free mice associated with human flora (HFA, n = 8), and in germ-free (n = 15) and holoxenic mice (n = 16).

Decreasing Albumin mRNA Expression in Cholangiocarcinomas along the Bile Duct Tree.

Introduction: The progressive technologies in albumin in situ hybridization (ISH) changed the routine application and the differential diagnosis of hepatic malignancies in the last years. The aim of the present work was to assess the diagnostic utility of albumin ISH on different cholangiocarcinoma (CCA) subtypes, as well as to assess how albumin production changes along the biliary tree.

Methods: Forty-five CCAs were retrospectively selected: 29 intrahepatic (15 small-duct and 14 large-duct subtypes), 7 perihilar, and 9 extrahepatic.

FGFR-targeted therapeutics: clinical activity, mechanisms of resistance and new directions.

Fibroblast growth factor (FGF) signalling via FGF receptors (FGFR1-4) orchestrates fetal development and contributes to tissue and whole-body homeostasis, but can also promote tumorigenesis. Various agents, including pan-FGFR inhibitors (erdafitinib and futibatinib), FGFR1/2/3 inhibitors (infigratinib and pemigatinib), as well as a range of more-specific agents, have been developed and several have entered clinical use. Erdafitinib is approved for patients with urothelial carcinoma harbouring FGFR2/3 alterations, and futibatinib and pemigatinib are approved for patients with cholangiocarcinoma harbouring FGFR2 fusions and/or rearrangements.

Activated FGFR2 signalling as a biomarker for selection of intrahepatic cholangiocarcinoma patients candidate to FGFR targeted therapies.

FGFR inhibitors have been developed to inhibit FGFR activation and signal transduction; notwithstanding, currently the selection of intrahepatic cholangiocarcinoma (iCCA) patients for these drugs only relies on the detection of FGFR2 genetic alterations (GAs) in tumor tissues or circulating tumor DNAs, without concomitant assessment of FGFR2 signalling status. Accordingly, we performed multi-omic analyses of FGFR2 genes and FGFR2 signalling molecules in the tissue samples from 36 iCCA naïve patients. Gain-of-function FGFR2 GAs were detected in 7 patients, including missense mutations (n = 3; p.

A signature of five 7-methylguanosine-related genes is a prognostic marker for lung squamous cell carcinoma.

Background: N-methylguanosine (m7G) is an important posttranscriptional modification affecting mRNA and tRNA functions and stability. The genes regulating the m7G process have been previously found involved in the carcinogenesis process. We aimed to analyze the role of m7G-related genes as potential prognostic markers for lung squamous cell carcinoma (LSCC).

Improvements in Systemic Therapies for Advanced Malignant Mesothelioma.

Malignant pleural mesothelioma (MPM) is a rare and aggressive malignancy associated with poor prognosis and a 5-year survival rate of 12%. Many drugs have been tested over the years with conflicting results. The aim of this review is to provide an overview of current therapies in MPM and how to best interpret the data available on these drugs.

Mutational Landscape of Cholangiocarcinoma According to Different Etiologies: A Review.

Recent next-generation sequencing (NGS) studies on large cohorts of cholangiocarcinoma (CCA) patients have clearly revealed the extreme intra- and inter-tumoral molecular heterogeneity that characterizes this malignancy. The lack of a stereotyped molecular signature in CCA makes the identification of actionable therapeutic targets challenging, making it mandatory to have a better understanding of the origin of such heterogeneity in order to improve the clinical outcome of these patients. Compelling evidence has shown that the CCA genomic landscape significantly differs according to anatomical subtypes and the underlying etiology, highlighting the importance of conducting molecular studies in different populations of CCA patients.

Asbestos exposure as an additional risk factor for small duct intrahepatic cholangiocarcinoma: a pilot study.

Intrahepatic cholangiocarcinoma (iCCA) is a rare malignancy, recently classified in small duct and large duct morphological subtypes. Growing evidence suggests asbestos as a putative risk factor for iCCA, albeit no correlation between asbestos and iCCA morphology has been investigated so far. The aim of the present study was to assess the relationship between asbestos exposure and iCCA morphological subtype.

axis promotes lung adenocarcinoma progression and energy metabolism reprogramming.

Background: Metabolic reprogramming is an emerging cancer feature that has recently drawn special attention since it promotes tumor cell growth and proliferation. However, the mechanism of the Warburg effect is still largely unknown. This research aimed to reveal the effects of BarH-like homeobox 2 () in regulating tumor progression and glucose metabolism in lung adenocarcinoma (LUAD).

Intensive Follow-Up Program and Oncological Outcomes of Biliary Tract Cancer Patients after Curative-Intent Surgery: A Twenty-Year Experience in a Single Tertiary Medical Center.

Aim: The aim of this research was to assess the impact of an intensive follow-up program on BTC patients who had received surgery with curative intent at a tertiary referral hospital.

Methods: BTC patients were followed-up every three months during the first two years after their first surgery and every six months from the third to the fifth post-operative year.

Results: A total of 278 BTC patients who received R0/R1 surgery were included.

Targeting STT3A produces an anti-tumor effect in lung adenocarcinoma by blocking the MAPK and PI3K/AKT signaling pathway.

Background: Glycosylation is crucial for the stability and biological functions of proteins. The aberrant glycosylation of critical proteins plays an important role in multiple cancers, including lung adenocarcinoma (LUAD). STT3 oligosaccharyltransferase complex catalytic subunit A (STT3A) is a major isoform of N-linked glycosyltransferase that catalyzes the glycosylation of various proteins.

Exposure to Asbestos and Increased Intrahepatic Cholangiocarcinoma Risk: Growing Evidences of a Putative Causal Link.

To date the true global incidence of intrahepatic cholangiocarcinoma (iCCA) and the underlying risk factors remain to be fully defined, in particular, the role of occupational and environmental factors. Currently, the putative role of asbestos exposure as a risk factor for iCCA is gaining increased attention in the international scientific community and agencies. In this commentary we review and integrate available epidemiological and mechanistic evidences that support a potential role of asbestos exposure in iCCA etiology.

Immunotherapy in Pancreatic Cancer: Why Do We Keep Failing? A Focus on Tumor Immune Microenvironment, Predictive Biomarkers and Treatment Outcomes.

The advent of immunotherapy and targeted therapies has dramatically changed the outcomes of patients affected by many malignancies. Pancreatic cancer (PC) remains one the few tumors that is not treated with new generation therapies, as chemotherapy still represents the only effective therapeutic strategy in advanced-stage disease. Agents aiming to reactivate the host immune system against cancer cells, such as those targeting immune checkpoints, failed to demonstrate significant activity, despite the success of these treatments in other tumors.

Predictive Biomarkers for Checkpoint Inhibitor-Based Immunotherapy in Hepatocellular Carcinoma: Where Do We Stand?

Hepatocellular carcinoma (HCC) remains the sixth most commonly diagnosed malignancy worldwide, still representing an important cause of cancer-related death. Over the next few years, novel systemic treatment options have emerged. Among these, immune checkpoint inhibitors (ICIs) have been widely evaluated and are under assessment, as monotherapy or in combination with other anticancer agents in treatment-naïve and previously treated patients.

Targeting BRAF-Mutant Biliary Tract Cancer: Recent Advances and Future Challenges.

Background: Biliary tract cancers (BTCs) represent a heterogeneous group of aggressive solid tumors with limited therapeutic options, and include gallbladder cancer (GBC), ampulla of Vater cancer (AVC), intrahepatic cholangiocarcinoma (iCCA) and extrahepatic cholangiocarcinoma (eCCA).

Methods & Results: In the current review, we will discuss recent results of clinical trials testing targeted therapies in BRAF-mutant BTCs, with a particular focus on the recently published Phase II ROAR trial and ongoing active and recruiting clinical trials.

Conclusions: Although the extended use of molecular profiling has paved the way toward a new era in BTC management, targeted therapies are limited to iCCA so far, and the prognosis of patients with metastatic disease has substantially not changed in the last decade.

Nivolumab: an investigational agent for the treatment of biliary tract cancer.

: Biliary tract cancers (BTCs) include four uncommon primary biliary malignancies characterized by poor prognosis: intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder cancer, and ampulla of Vater cancer. To date, the available therapeutic options are limited; nevertheless, with the advent of targeted therapy and immunotherapy, the treatment scenario is constantly changing, opening toward future possibilities for the personalized treatment of BTC. Among these treatments, nivolumab is currently being investigated in BTC.

Molecular Features and Targeted Therapies in Extrahepatic Cholangiocarcinoma: Promises and Failures.

Biliary tract cancers (BTCs) include a heterogenous group of aggressive malignancies with limited therapeutic options. According to their anatomical location, these hepatobiliary tumors are usually classified into intrahepatic cholangiocarcinoma (iCCA), extrahepatic cholangiocarcinoma (eCCA), and gallbladder cancer (GBC). Unfortunately, BTCs are often diagnosed when already metastatic, and although the advent of genomic sequencing has led to a deeper understanding of iCCA pathogenesis, very little data are currently available about the molecular landscape of eCCA.

The (Eternal) Debate on Microwave Ablation Radiofrequency Ablation in BCLC-A Hepatocellular Carcinoma.

Background/aim: While percutaneous radiofrequency ablation (RFA) is considered the standard ablative modality for the treatment of early-stage hepatocellular carcinoma (HCC), percutaneous microwave ablation (MWA) is being increasingly used in recent years. We performed a systematic review and meta-analysis to compare percutaneous MWA versus percutaneous RFA in BCLC-A HCC across randomized controlled trials (RCTs).

Patients And Methods: Eligible studies included RCTs assessing MWA versus RFA in BCLC-A HCC.