Impact of remnant vital tissue after locoregional treatment and liver transplant in hepatocellular cancer patients. A multicentre cohort study

The role of pathological findings after locoregional treatments as predictors of hepatocellular cancer recurrence after liver transplantation has been poorly addressed. The aim of the study was to identify the role of remnant vital tissue (RVT) of the target lesion in predicting hepatocellular cancer recurrence. Two hundred and seventy-six patients firstly undergoing locoregional treatment and then transplanted between January 2010 and December 2015 in four European Transplant Centres (i.e. Rome Tor Vergata, Birmingham, Brussels and Ancona) were enrolled in the study to investigate the role of pathological response at upfront locoregional treatment. At multivariable Cox regression analysis, RVT ≥2 cm was a strong independent risk factor for post-LT recurrence (HR = 5.6; P < 0.0001). Five-year disease-free survival rates were 60.8%, 80.9% and 95.0% in patients presenting a RVT ≥2 cm vs. 0.1-1.9 vs. no RVT, respectively. When only Milan Criteria-IN patients were analysed, similar results were reported, with 5-year disease-free survival rates of 58.1%, 79.0% and 94.0% in patients presenting a RVT ≥2 cm vs. 0.1-1.9 vs. no RVT, respectively. RVT is an important determinant of tumour recurrence after liver transplantation performed for hepatocellular cancer. Its discriminative power looks to be evident also in a Milan-IN setting, suggesting to more liberally use locoregional treatments also in these patients

Notch3 drives development and progression of cholangiocarcinoma

The prognosis of cholangiocarcinoma (CC) is dismal. Notch has been identified as a potential driver; forced exogenous overexpression of Notch1 in hepatocytes results in the formation of biliary tumors. In human disease, however, it is unknown which components of the endogenously signaling pathway are required for tumorigenesis, how these orchestrate cancer, and how they can be targeted for therapy. Here we characterize Notch in human-resected CC, a toxin-driven model in rats, and a transgenic mouse model in which p53 deletion is targeted to biliary epithelia and CC induced using the hepatocarcinogen thioacetamide. We find that across species, the atypical receptor NOTCH3 is differentially overexpressed; it is progressively up-regulated with disease development and promotes tumor cell survival via activation of PI3k-Akt. We use genetic KO studies to show that tumor growth significantly attenuates after Notch3 deletion and demonstrate signaling occurs via a noncanonical pathway independent of the mediator of classical Notch, Recombinant Signal Binding Protein for Immunoglobulin Kappa J Region (RBPJ). These data present an opportunity in this aggressive cancer to selectively target Notch, bypassing toxicities known to be RBPJ dependent

Intrahepatic cholangiocarcinoma: histological diversity and the role of the pathologist

Intrahepatic cholangiocarcinoma (iCCA) is one of the primary liver cancers and presents with tumor heterogeneity. About 50% of iCCAs comprise actionable mutations, which completely change patient management. In addition, the precise diagnosis of iCCA, including subtype, has become crucial, and pathologists play an important role in this regard. This review focuses on iCCA heterogeneity; looking at different perspectives to guide diagnosis and optimal treatment choice

A Review on the Update of Combined Hepatocellular Cholangiocarcinoma.

Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a primary liver tumor with neoplastic components of both hepatocytic and cholangiocytic differentiation. This unique neoplasm is gaining increasing recognition due to the intriguing pathology, tumor biology, and clinical behavior. It also poses challenges in diagnosis, treatment, and research, largely because of its histological and phenotypic diversity that lead to confusion in terminology and classification. There have been efforts attempting to unify the terminology of this neoplasm recently. Advances in investigation in various aspects have also been made. This review aims to update the terminology, classification, and clinical and pathological characteristics of cHCC-CCA

A rare synchronous B-cell and T-cell PTLD in the liver: a challenging differential diagnosis with rejection

info:eu-repo/semantics/publishe

Metabolic iron disorder after liver transplant: Hereditary hemochromatosis in a pediatric recipient of a pediatric donor with unknown HFE C282Y homozygous mutation.

We report a case of an iron overload syndrome twenty years after a liver transplantation in a patient without feature for secondary iron overload. The diagnosis of hemochromatosis with homozygous mutationC282Y in the graft was made possible with liver biopsy, using real-time PCR technique with Light-Cycler 480. Our case suggests that in case of iron overload syndrome after liver transplantation we can perform a liver biopsy with real-time PCR technique that allows us to search for the mutation of the HFE

Severe panniculitis and polyarthritis caused by acinar cell carcinoma arising from an ectopic pancreas

The pancreatitis, panniculitis and polyarthritis (PPP) syndrome is a rare condition caused by pancreatic diseases, such as acute or chronic pancreatitis or pancreatic carcinoma. We report the first case of PPP syndrome caused by metastatic acinar cell carcinoma from an ectopic pancreas. The symptoms were successfully managed by the treatment of the metastatic carcinoma. Pancreatic cytosteatonecrosis should be always considered in a patient who is showing symptoms of panniculitis and polyarthritis

Impact of liver inflammation on whole body insulin resistance : a case report on primary biliary cholangitis.

Chronic liver diseases such as hepatitis C or non-alcoholic fatty liver disease could be associated with insulin resistance, even in the absence of cirrhosis or significant fibrosis. In this report, we present the case of a patient who was diagnosed with primary biliary cholangitis and metabolic syndrome. Initial evaluation also revealed diabetes with elevated fasting plasma glucose and glycated hemoglobin. After eight weeks of treatment with ursodeoxycholic acid, a complete normalization of the hepatic biological tests was observed. A few months later, while body weight and abdominal perimeter remained stable, fasting blood glucose and glycated hemoglobin decreased significantly, compatible with diabetes disappearance. This finding supports the concept that the inflamed liver plays a major role in the pathogenesis of insulin resistance and diabetes occurrence in chronic liver diseases, including primary biliary cholangitis