Oral Microbiome Signatures as Potential Biomarkers for Gastric Cancer Risk Assessment.

Background: Gastric cancer (GC) is the fifth leading cause of cancer-related death worldwide. The oral microbiota was investigated for distinguishable characteristics between GC, premalignant gastric conditions (Pre-GC), and control participants.

Methods: Mouthwash samples from GC, Pre-GC, and control participants at a tertiary care center were prospectively collected.

Acalculous cholecystitis- an imaging and therapeutic update.

In this review, we highlight current understanding of the pathogenesis of acalculous cholecystitis, as well as its key imaging and clinical features. We also review what happens after a diagnosis and outline current interventional methods.

Endoscopic devices and techniques for the management of gastric varices (with videos).

Background And Aims: Gastric variceal bleeding occurs less commonly than bleeding from esophageal varices (EVs), although it is associated with higher morbidity and mortality. Bleeding from gastroesophageal varices type 1 (GOV1) is treated like EVs. In contrast, other forms of gastric variceal bleeding, including gastroesophageal varices type 2 (GOV2) and isolated gastric varices types 1 (IGV1) and 2 (IGV2), are treated with varying endoscopic approaches.

Targetable treatment resistance in thyroid cancer with clonal hematopoiesis.

Anaplastic thyroid cancer (ATC) is a clinically aggressive malignancy with a dismal prognosis. Combined BRAF/MEK inhibition offers significant therapeutic benefit in patients with -mutant ATCs. However, relapses are common and overall survival remains poor.

Jak2V617F Reversible Activation Shows Its Essential Requirement in Myeloproliferative Neoplasms.

Unlabelled: Gain-of-function mutations activating JAK/STAT signaling are seen in the majority of patients with myeloproliferative neoplasms (MPN), most commonly JAK2V617F. Although clinically approved JAK inhibitors improve symptoms and outcomes in MPNs, remissions are rare, and mutant allele burden does not substantively change with chronic therapy. We hypothesized this is due to limitations of current JAK inhibitors to potently and specifically abrogate mutant JAK2 signaling.

A reversible epigenetic memory of inflammatory injury controls lineage plasticity and tumor initiation in the mouse pancreas.

Inflammation is essential to the disruption of tissue homeostasis and can destabilize the identity of lineage-committed epithelial cells. Here, we employ lineage-traced mouse models, single-cell transcriptomic and chromatin analyses, and CUT&TAG to identify an epigenetic memory of inflammatory injury in the pancreatic acinar cell compartment. Despite resolution of pancreatitis, our data show that acinar cells fail to return to their molecular baseline, with retention of elevated chromatin accessibility and H3K4me1 at metaplasia genes, such that memory represents an incomplete cell fate decision.

Predicting tumour content of liquid biopsies from cell-free DNA.

Background: Liquid biopsy is a minimally-invasive method of sampling bodily fluids, capable of revealing evidence of cancer. The distribution of cell-free DNA (cfDNA) fragment lengths has been shown to differ between healthy subjects and cancer patients, whereby the distributional shift correlates with the sample's tumour content. These fragmentomic data have not yet been utilised to directly quantify the proportion of tumour-derived cfDNA in a liquid biopsy.

CXCL8/CXCR2 signaling mediates bone marrow fibrosis and is a therapeutic target in myelofibrosis.

Proinflammatory signaling is a hallmark feature of human cancer, including in myeloproliferative neoplasms (MPNs), most notably myelofibrosis (MF). Dysregulated inflammatory signaling contributes to fibrotic progression in MF; however, the individual cytokine mediators elicited by malignant MPN cells to promote collagen-producing fibrosis and disease evolution are yet to be fully elucidated. Previously, we identified a critical role for combined constitutive JAK/STAT and aberrant NF-κB proinflammatory signaling in MF development.

TET2 guards against unchecked BATF3-induced CAR T cell expansion.

Further advances in cell engineering are needed to increase the efficacy of chimeric antigen receptor (CAR) and other T cell-based therapies. As T cell differentiation and functional states are associated with distinct epigenetic profiles, we hypothesized that epigenetic programming may provide a means to improve CAR T cell performance. Targeting the gene that encodes the epigenetic regulator ten-eleven translocation 2 (TET2) presents an interesting opportunity as its loss may enhance T cell memory, albeit not cause malignancy.

What Every Gastroenterologist Should Know About Gastrointestinal NETs.

Gastrointestinal neuroendocrine tumors are increasingly common. Practitioners should examine these lesions carefully found on routine endoscopy. Obtaining accurate neuroendocrine tumors stage and grade is critical to patient assessment and management, and assistance from advanced endoscopists may be needed.

Use of endoluminal vacuum therapy after anastomotic leak in a gynecologic oncology patient with rectosigmoid resection: A case report.

•Anastomotic leak is an infrequent complication after colon resection and is associated with high morbidity and mortality.•Endoluminal vacuum therapy (EVAT) promotes wound closure by covering anastomotic leaks intraluminally and applying vacuum.•EVAT has been shown to be safe with mild adverse events.

Serum Pepsinogen as a Biomarker for Gastric Cancer in the United States: A Nested Case-Control Study Using the PLCO Cancer Screening Trial Data.

Background: Gastric cancer lacks specific symptoms, resulting in diagnosis at later stages and high mortality. Serum pepsinogen is a biomarker for atrophic gastritis, a gastric cancer precursor, and may be useful to detect persons at increased risk of gastric cancer.

Methods: The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial was conducted in the United States between 1993 and 2001.

Devices for esophageal function testing.

Background And Aims: Esophageal function testing is an integral component of the evaluation of refractory GERD and esophageal motility disorders. This review summarizes the current technologies available for esophageal function testing, including the functional luminal imaging probe (FLIP), high-resolution esophageal manometry (HRM), and multichannel intraluminal impedance (MII) and pH monitoring.

Methods: We performed a MEDLINE, PubMed, and MAUDE database literature search to identify pertinent clinical studies through March 2021 using the following key words: esophageal manometry, HRM, esophageal impedance, FLIP, MII, and esophageal pH testing.

Scaffold attachment factor B1 regulates androgen degradation pathways in prostate cancer.

The nuclear matrix protein Scaffold Attachment Factor B1 (SAFB1, ) can act in prostate cancer (PCa) as an androgen receptor (AR) co-repressor that functions through epigenetic silencing of AR targets, such as prostate specific antigen (PSA, ). Genomic profiling of SAFB1-silenced PCa cells indicated that SAFB1 may play a role in modulating intracrine androgen levels through the regulation of UDP-glucuronosyltransferase (UGT) genes, which inactivate steroid hormones. Gene silencing of SAFB1 resulted in increased levels of free dihydrotesterosterone (DHT), and increased resistance to the AR inhibitor enzalutamide.

Endoscopic therapies for gallbladder drainage.

Background And Aims: Endoscopic management of acute cholecystitis has expanded in patients who are considered nonoperative candidates. Traditionally managed with percutaneous cholecystostomy (PC), improvement in techniques and devices has led to increased use of endoscopic methods for gallbladder drainage. This document reviews technical aspects of endoscopic transpapillary gallbladder drainage (ET-GBD) and EUS-guided GBD (EUS-GBD) as well as their respective technical/clinical success and adverse event rates.

Lumen-apposing metal stents (with videos).

Background And Aims: Lumen-apposing metal stents (LAMSs) are a novel class of devices that have expanded the spectrum of endoscopic GI interventions. LAMSs with their dumbbell configuration, short saddle length, and large inner luminal diameter provide favorable stent characteristics to facilitate anastomosis formation between the gut lumen and adjacent structures.

Methods: The MEDLINE database was searched through April 2021 for articles related to LAMSs by using additional relevant keywords such as "walled-off pancreatic necrosis," "pseudocysts," "pancreatic fluid collection," "cholecystitis," "gastroenterostomy," in addition to "endoscopic treatment" and "endoscopic management," among others.

Clinical and economic impacts of large volume delayed sampling and pathogen reduction technology platelet processing strategies in the United States.

Background: Large volume delayed sampling (LVDS) and pathogen reduction technology (PRT) are strategies for platelet processing to minimize transfusion of contaminated platelet components (PCs). This study holistically compares the economic and clinical impact of LVDS and PRT in the United States.

Study Design And Methods: A decision model was constructed to simulate collection, processing, and use of PCs and to compare processing strategies: PRT with 5-day shelf life, LVDS with 7-day shelf life (LVDS7), and LVDS with 5-day shelf life extended to 7 days with secondary testing (LVDS5/2).

Enhanced specificity of clinical high-sensitivity tumor mutation profiling in cell-free DNA via paired normal sequencing using MSK-ACCESS.

Circulating cell-free DNA from blood plasma of cancer patients can be used to non-invasively interrogate somatic tumor alterations. Here we develop MSK-ACCESS (Memorial Sloan Kettering - Analysis of Circulating cfDNA to Examine Somatic Status), an NGS assay for detection of very low frequency somatic alterations in 129 genes. Analytical validation demonstrated 92% sensitivity in de-novo mutation calling down to 0.