Extrahepatic Y Complication; Gastric Ulcer Secondary to Y Therapy for Liver Metastasis Despite Negative Preprocedural Imaging.

Transarterial radioembolization using yttrium-90 (Y) therapy has become a standard modality of treatment for primary and metastatic liver malignancies due to its high efficacy rate and relatively low risk of adverse effects compared to other forms of locoregional and systemic therapies. Non-target distribution of radio embolic beads and adjacent structure radiation are the two most common adverse effects. However, these are rarely encountered due to thorough imaging and mapping studies prior to Y therapy.

Confocal laser endomicroscope with distal MEMS scanner for real-time histopathology.

Confocal laser endomicroscopy is an emerging methodology to perform real time optical biopsy. Fluorescence images with histology-like quality can be collected instantaneously from the epithelium of hollow organs. Currently, scanning is performed at the proximal end of probe-based instruments used routinely in the clinic, and flexibility to control the focus is limited.

Mapping the adult human esophagus in vivo and in vitro.

Many esophageal diseases can arise during development or throughout life. Therefore, well-characterized in vitro models and detailed methods are essential for studying human esophageal development, homeostasis and disease. Here, we (1) create an atlas of the cell types observed in the normal adult human esophagus; (2) establish an ancestrally diverse biobank of in vitro esophagus tissue to interrogate homeostasis and injury; and (3) benchmark in vitro models using the adult human esophagus atlas.

Phase II trial of weekly erlotinib dosing to reduce duodenal polyp burden associated with familial adenomatous polyposis.

Importance: Patients with familial adenomatous polyposis (FAP) are at markedly increased risk for duodenal adenomas and cancer. Combination sulindac and erlotinib was previously shown to reduce duodenal polyp burden but was associated with a relatively high adverse event (AE) rate.

Objective: To evaluate if a once weekly dosing schedule for erlotinib intervention improves the AE profile, while still providing efficacy with respect to reduced polyp burden, in participants with FAP.

Proanthocyanidins mitigate bile acid-induced changes in GSTT2 levels in a panel of racially diverse patient-derived primary esophageal cell cultures.

Persistent and symptomatic reflux of gastric and duodenal contents, known as gastroesophageal reflux disease (GERD), is the strongest risk factor for esophageal adenocarcinoma (EAC). Despite similar rates of GERD and other risk factors across racial groups, EAC progression disproportionately impacts Caucasians. We recently reported that elevated tissue levels of the detoxification enzyme GSTT2 in the esophagi of Blacks compared to Caucasians may contribute protection.

UBCH5 Family Members Differentially Impact Stabilization of Mutant p53 via RNF128 Iso1 During Barrett's Progression to Esophageal Adenocarcinoma.

Background & Aims: TP53 mutations underlie Barrett's esophagus (BE) progression to dysplasia and cancer. During BE progression, the ubiquitin ligase (E3) RNF128/GRAIL switches expression from isoform 2 (Iso2) to Iso1, stabilizing mutant p53. However, the ubiquitin-conjugating enzyme (E2) that partners with Iso1 to stabilize mutant p53 is unknown.

Prostaglandin E, Produced by Mast Cells in Colon Tissues From Patients With Irritable Bowel Syndrome, Contributes to Visceral Hypersensitivity in Mice.

Background And Aims: Visceral hypersensitivity is common in patients with irritable bowel syndrome (IBS). We investigated whether inflammatory molecules, such as histamine and proteases, activate prostaglandin-endoperoxide synthase 2 (also called COX2) to increase the synthesis of prostaglandin E (PGE2) by mast cells, which activates the receptor PTGER2 (also called EP2) in the dorsal root ganglia to promote visceral hypersensitivity.

Methods: We used an enzyme-linked immunosorbent assay to measure levels of spontaneous release of molecules from mast cells in colonic mucosa from patients with IBS with diarrhea (IBS-D; 18 women and 5 men; aged 28-60 years), healthy individuals (controls, n = 24), mice, and rats.

Targeted imaging of esophageal neoplasia with a fluorescently labeled peptide: first-in-human results.

Esophageal adenocarcinoma is rising rapidly in incidence and usually develops from Barrett's esophagus, a precursor condition commonly found in patients with chronic acid reflux. Premalignant lesions are challenging to detect on conventional screening endoscopy because of their flat appearance. Molecular changes can be used to improve detection of early neoplasia.

Relationships between serum and colon concentrations of carotenoids and fatty acids in randomized dietary intervention trial.

Little is known about the effect of preventive diets on colonic nutrient concentrations. This study randomized 120 persons at increased risk of colon cancer to a Mediterranean versus a Healthy Eating diet for six months. The former targeted increases in whole grains, fruits, vegetables, monounsaturated, and n3 fats.

Effect of ginger root on cyclooxygenase-1 and 15-hydroxyprostaglandin dehydrogenase expression in colonic mucosa of humans at normal and increased risk for colorectal cancer.

Elevated tissue levels of prostaglandin E2, produced by cyclooxygenase (COX), are an early event in colorectal cancer (CRC). Data suggest the efficacy of nonsteroidal anti-inflammatory drugs, such as cancer preventives, in the inhibition of COX activity; however, side effects of nonsteroidal anti-inflammatory pose unacceptable limitations. Ginger has been reported to have anti-inflammatory activities with significant CRC preventive potential.

Microsatellite instability and DNA mismatch repair protein deficiency in Lynch syndrome colorectal polyps.

Colorectal cancers associated with Lynch syndrome are characterized by deficient DNA mismatch repair (MMR) function. Our aim was to evaluate the prevalence of microsatellite instability (MSI) and loss of MMR protein expression in Lynch syndrome-associated polyps. Sixty-two colorectal polyps--37 adenomatous polyps, 23 hyperplastic polyps, and 2 sessile serrated polyps (SSP)--from 34 subjects with germline MMR gene mutations were tested for MSI using a single pentaplex PCR for five mononucleotide repeat microsatellite markers, and also for expression of MLH1, MSH2, MSH6, and PMS2 proteins by immunohistochemistry.

Phase IIa clinical trial of curcumin for the prevention of colorectal neoplasia.

Curcumin is derived from the spice tumeric and has antiinflammatory and antineoplastic effects in vitro and in animal models, including preventing aberrant crypt foci (ACF) and adenomas in murine models of colorectal carcinogenesis. Inhibiting the production of the procarcinogenic eicosanoids prostaglandin E₂ (PGE₂) and 5-hydroxyeicosatetraenoic acid (5-HETE) can suppress carcinogenesis in rodents. Curcumin reduces mucosal concentrations of PGE₂ (via inhibition of cyclooxygenases 1 and 2) and 5-HETE (via inhibition of 5-lipoxygenase) in rats.

Affinity peptide for targeted detection of dysplasia in Barrett's esophagus.

Background & Aims: Dysplasia is a premalignant condition in Barrett's esophagus that is difficult to detect on endoscopy because of its flat architecture and patchy distribution. Peptides are promising for use as novel molecular probes that identify cell surface targets unique to disease and can be fluorescence-labeled for detection. We aim to select and validate an affinity peptide that binds to esophageal dysplasia for future clinical studies.

Plasma glycoprotein profiling for colorectal cancer biomarker identification by lectin glycoarray and lectin blot.

Colorectal cancer (CRC) remains a major worldwide cause of cancer-related morbidity and mortality largely due to the insidious onset of the disease. The current clinical procedures utilized for disease diagnosis are invasive, unpleasant, and inconvenient; hence, the need for simple blood tests that could be used for the early detection of CRC. In this work, we have developed methods for glycoproteomics analysis to identify plasma markers with utility to assist in the detection of colorectal cancer (CRC).