Gastroenterology

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BACKGROUND & AIMS: Nationwide organized gastric cancer (GC) screening programs have been running for decades in South Korea and Japan. This study aimed to conduct a quasi-experimental analysis to assess the population impact of these programs on GC mortality. METHODS: We used the flexible synthetic control method (SCM) to estimate the effect of the screening programs on age-standardized GC mortality and other upper gastrointestinal (UGI) diseases (esophageal cancer and peptic ulcer) among people aged 40 years or above...

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BACKGROUND & AIMS: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract, and it has high metastatic and recurrence rates. We aimed to characterize the proteomic features of GIST to understand biological processes and treatment vulnerabilities. METHODS: Quantitative proteomics and phosphoproteomics analyses were performed on 193 GIST patients to reveal the biological characteristics of GIST. Data-driven hypotheses were tested by performing functional experiments utilizing both GIST cell lines and xenograft mouse models...

BACKGROUND & AIMS: Chronic inflammation surrounding bile ducts contributes to the disease pathogenesis of most cholangiopathies. Poor efficacy of immunosuppression in these conditions suggests biliary-specific pathological principles. Here we perform biliary niche specific functional interpretation of a causal mutation (CD100 K849T) of primary sclerosing cholangitis (PSC) to understand related pathogenic mechanisms. METHODS: Biopsies of explanted livers and endoscopy-guided sampling were used to assess the CD100 expression by spatial transcriptomics, immune imaging, and high-dimensional flow cytometry...

DESCRIPTION: Cirrhosis is a major cause of morbidity and mortality in the United States and worldwide. It consists of compensated, decompensated, and further decompensated stages; median survival is more than 15 years, 2 years, and 9 months for each stage, respectively. With each stage, there is progressive worsening of portal hypertension and the vasodilatory-hyperdynamic circulatory state, resulting in a progressive decrease in effective arterial blood volume and renal perfusion. Vasoconstrictors reduce portal pressure via splanchnic vasoconstriction and are used in the management of variceal hemorrhage...

BACKGROUND & AIMS: RET tyrosine kinase is necessary for enteric nervous system (ENS) development. Loss-of-function RET mutations cause Hirschsprung disease (HSCR), in which infants are born with aganglionic bowel. Despite surgical correction, HSCR patients often experience chronic defecatory dysfunction and enterocolitis, suggesting that RET is important after development. To test this hypothesis, we determined the location of postnatal RET and its significance in gastrointestinal (GI) motility...

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