Time-Restricted Feeding Attenuates Metabolic Dysfunction-Associated Steatohepatitis and Hepatocellular Carcinoma in Obese Male Mice.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has surpassed the hepatitis B virus and hepatitis C virus as the leading cause of chronic liver disease in most parts of the Western world. MASLD (formerly known as NAFLD) encompasses both simple steatosis and more aggressive metabolic dysfunction-associated steatohepatitis (MASH), which is accompanied by inflammation, fibrosis, and cirrhosis, and ultimately can lead to hepatocellular carcinoma (HCC). There are currently very few approved therapies for MASH.

Primary extrahepatic biliary neuroendocrine tumor: a case report.

Extrahepatic biliary neuroendocrine tumors (EBNETs) are extremely rare and difficult to diagnose. The vast majority are diagnosed postoperatively on histological evaluation of surgical specimens. Workup and treatment principles are largely based on retrospective series and case reports.

Comparison of cold snare and hot snare polypectomy for the resection of sporadic nonampullary duodenal adenomas.

Background And Aims: Nonampullary duodenal adenomas can undergo malignant transformation, making endoscopic resection, often by hot snare (HSP) or cold snare polypectomy (CSP), necessary. Although CSP has been shown to be safer for removal of colon polyps, data comparing these techniques for the resection of duodenal adenomas are limited. Our aim was to compare the safety and efficacy of CSP and HSP for the removal of nonampullary duodenal adenomas.

Hepatocyte Deletion of IGF2 Prevents DNA Damage and Tumor Formation in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Serine-arginine rich splicing factor 3 (SRSF3) plays a critical role in hepatocyte function and its loss in mice promotes chronic liver damage and leads to HCC. Hepatocyte-specific SRSF3 knockout mice (SKO mice) also overexpress insulin-like growth factor 2 (IGF2).

ASK1 inhibition reduces cell death and hepatic fibrosis in an Nlrp3 mutant liver injury model.

Hepatic inflammasome activation is considered a major contributor to liver fibrosis in NASH. Apoptosis signal-regulating kinase 1 (ASK1) is an apical mitogen-activated protein kinase that activates hepatic JNK and p38 to promote apoptosis, inflammation, and fibrosis. The aim of the current study was to investigate whether pharmacologic inhibition of ASK1 could attenuate hepatic fibrosis driven by inflammasome activation using gain-of-function NOD-like receptor protein 3 (Nlrp3) mutant mice.

Degradation of splicing factor SRSF3 contributes to progressive liver disease.

Serine rich splicing factor 3 (SRSF3) plays a critical role in liver function and its loss promotes chronic liver damage and regeneration. As a consequence, genetic deletion of SRSF3 in hepatocytes caused progressive liver disease and ultimately led to hepatocellular carcinoma. Here we show that SRSF3 is decreased in human liver samples with non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), or cirrhosis that was associated with alterations in RNA splicing of known SRSF3 target genes.

Dysregulation of serum bile acids and FGF19 in alcoholic hepatitis.

Background & Aims: The degree of cholestasis is an important disease driver in alcoholic hepatitis, a severe clinical condition that needs new biomarkers and targeted therapies. We aimed to identify the largely unknown mechanisms and biomarkers linked to cholestasis in alcoholic hepatitis.

Methods: Herein, we analyzed a well characterized cohort of patients with alcoholic hepatitis and correlated clinical and histological parameters and outcomes with serum bile acids and fibroblast growth factor 19 (FGF19), a major regulator of bile acid synthesis.

Hodgkin's lymphoma with unusual pulmonary presentations: Reporting two cases.

Classical Hodgkin's lymphoma (CHL) presenting with exclusively pulmonary symptoms is very unusual. We report two cases of CHL with atypical clinical presentations mimicking pulmonary infections. The first case represents a stage IV CHL with secondary lung involvement, and the second case demonstrates a very rare case of CHL with isolated lung involvement, also known as primary pulmonary Hodgkin's lymphoma.

Well-Differentiated Neuroendocrine Tumors with a Morphologically Apparent High-Grade Component: A Pathway Distinct from Poorly Differentiated Neuroendocrine Carcinomas.

Purpose: Most well-differentiated neuroendocrine tumors (WD-NET) of the enteropancreatic system are low-intermediate grade (G1, G2). Elevated proliferation demonstrated by either a brisk mitotic rate (>20/10 high power fields) or high Ki-67 index (>20%) defines a group of aggressive neoplasms designated as high-grade (G3) neuroendocrine carcinoma (NEC). High-grade NEC is equated with poorly differentiated NEC (PD-NEC) and is associated with a dismal outcome.

Anaplastic Transformation of Papillary Thyroid Cancer in the Retroperitoneum.

Anaplastic thyroid carcinoma is an aggressive variant of thyroid cancer that in most cases arises from anaplastic transformation of terminally differentiated thyroid carcinomas. This process usually occurs in the thyroid or cervical lymph nodes. Anaplastic transformation in distant metastatic sites is exceedingly rare, only previously documented in a few case reports.

Mixed acinar-endocrine carcinoma of the pancreas: new clinical and pathological features in a contemporary series.

Objective: The objective of this study was to characterize the novel clinical and pathological features of mixed acinar-endocrine carcinoma of the pancreas.

Methods: This was a retrospective review of medical records and surgical pathology specimens of patients with a diagnosis of mixed acinar-endocrine carcinoma of the pancreas at Cedars-Sinai Medical Center between 2005 and 2011. Additional immunohistochemistry was performed on the specimens of some patients.

Noninvasive determination of endothelial cell function in the microcirculation in Kawasaki syndrome.

The aim of the study was to noninvasively assess endothelial cell (EC) function in the microcirculation using laser Doppler fluximetry (LDF) in acute and convalescent Kawasaki syndrome (KS) patients and healthy controls. KS is an acute, self-limited vasculitis of childhood that affects the EC of medium-sized arteries. No studies have addressed EC function in the peripheral microcirculation.

A novel, helper-dependent, adenovirus-retrovirus hybrid vector: stable transduction by a two-stage mechanism.

We have developed a novel vector system that uses a helper-dependent adenoviral vector as a carrier to deliver a fully functional retrovirus vector. The helper-dependent adenovirus (HDAd) can accommodate large inserts, provide high titers, and infect nondividing as well as dividing cells. However, adenoviral DNA is rarely integrated into the host cell genome, and its episomal expression is transient.