Gastric-like (pseudopyloric and pseudofoveolar) metaplasia and Paneth cell hyperplasia-neglected histological features of chronic ileal inflammation.

Architectural distortion and basal plasmacytosis are the most widely recognized histologic features of chronic ileal inflammation. However, these features might be difficult to assess in small, poorly oriented, or superficial biopsies. Additional features of chronic mucosal damage, including pseudopyloric or pseudofoveolar metaplasia and Paneth cell hyperplasia, have been less commonly reported, and their broader appreciation could facilitate the diagnosis of chronic ileal inflammatory conditions.

Dysplasia Detected in Patients With Serrated Epithelial Change Is Frequently Associated With an Invisible or Flat Endoscopic Appearance, Nonconventional Dysplastic Features, and Advanced Neoplasia.

The significance of serrated epithelial change (SEC), defined as endoscopically invisible hyperplastic polyp (HP)-like mucosal change identified in patients with inflammatory bowel disease (IBD), remains unclear. Although some studies reported an increased risk of synchronous and/or metachronous colorectal neoplasia in patients with SEC, including advanced neoplasia (high-grade dysplasia or colorectal cancer), the development of SEC is not significantly associated with increased colonic inflammation. This contrasts with the reported positive correlation between increased colonic inflammation and the risk of colorectal neoplasia in ulcerative colitis, arguing against the notion that SEC may represent a form of dysplasia.

Nonconventional Dysplasia is Frequently Associated With Goblet Cell Deficient and Serrated Variants of Colonic Adenocarcinoma in Inflammatory Bowel Disease.

Various subtypes of nonconventional dysplasia have been recently described in inflammatory bowel disease (IBD). We hypothesized that goblet cell deficient dysplasia and serrated dysplasia may be the primary precursor lesions for goblet cell deficient (GCDAC) and serrated (SAC) variants of colonic adenocarcinoma, respectively. Clinicopathologic features of 23 GCDAC and 10 SAC colectomy cases were analyzed.

Biomarker Analysis from a Phase I/Ib Study of Regorafenib and Nivolumab in Mismatch Repair-Proficient Advanced Refractory Colorectal Cancer.

Previously, we reported the modest but durable anticancer activity of regorafenib/nivolumab in mismatch repair-proficient (pMMR) refractory colorectal cancer in our I/Ib study. Our finding suggests the necessity of biomarkers for better selection of patients. Baseline clinical and pathological characteristics, blood and tumor samples from the patients in the trial were collected and evaluated to discover potential biomarkers.

Neuregulin-1β Improves Uremic Cardiomyopathy and Renal Dysfunction in Rats.

Chronic kidney disease is a global health problem affecting 10% to 12% of the population. Uremic cardiomyopathy is often characterized by left ventricular hypertrophy, fibrosis, and diastolic dysfunction. Dysregulation of neuregulin-1β signaling in the heart is a known contributor to heart failure.

Genomic Landscape of Normal and Breast Cancer Tissues in a Hungarian Pilot Cohort.

A limited number of studies have focused on the mutational landscape of breast cancer in different ethnic populations within Europe and compared the data with other ethnic groups and databases. We performed whole-genome sequencing of 63 samples from 29 Hungarian breast cancer patients. We validated a subset of the identified variants at the DNA level using the Illumina TruSight Oncology (TSO) 500 assay.

Non-conventional dysplasia is frequently associated with low-grade tubuloglandular and mucinous adenocarcinomas in inflammatory bowel disease.

There is limited information regarding the clinicopathological features of low-grade tubuloglandular (LGTGA) and mucinous (MAC) adenocarcinomas occurring in inflammatory bowel disease (IBD), especially with regard to their precursor lesions. METHODS AND RESULTS: Forty-six IBD colectomy specimens with LGTGA (n = 17) or MAC (n = 29) with adjacent precursor lesions were analysed. As controls, 12 IBD colectomy specimens with well- to moderately differentiated adenocarcinoma that lacked any mucinous, signet ring cell, low-grade tubuloglandular or serrated features were also analysed.

Biomarker analysis from a phase II multi-institutional study of nivolumab in patients with advanced refractory biliary tract cancer.

Background: Our previous phase II study demonstrated that nivolumab provides modest but durable clinical efficacy in patients with refractory biliary tract cancer, suggesting the significant clinical benefit of nivolumab in selected patients and the necessity of predictive biomarkers. We evaluated clinicopathological characteristics and tumour microenvironment of the patients who were enrolled the trial to identify potential biomarkers.

Methods: Baseline clinicopathological characteristics and pretreatment tumour samples were collected.

A phase I/Ib study of regorafenib and nivolumab in mismatch repair proficient advanced refractory colorectal cancer.

Aim: In contrast to mismatch repair deficient (dMMR) colorectal cancer (CRC), mismatch repair proficient (pMMR) CRC is usually unresponsive to anti-PD-1 immunotherapy. Recent preclinical data suggest that regorafenib may enhance the antitumor activity of anti-PD-1 immunotherapy. However, the safety and efficacy of regorafenib plus nivolumab have not been established in patients with refractory metastatic pMMR CRC.

Subtyping intestinal metaplasia in patients with chronic atrophic gastritis: an interobserver variability study.

Incomplete gastric intestinal metaplasia (GIM) is associated with an increased risk of gastric cancer. We aimed to examine the interobserver variability of GIM subtyping (incomplete vs complete) in histological diagnosis of patients with chronic atrophic gastritis and to identify factors with potential impact on agreement. Nine international gastrointestinal expert pathologists assessed 46 cases with complete, incomplete or mixed-type GIM on scanned haematoxylin and eosin (H&E)-stained slides.

Exercise training worsens cardiac performance in males but does not change ejection fraction and improves hypertrophy in females in a mouse model of metabolic syndrome.

Background: Metabolic syndrome (MetS) refers to a cluster of co-existing cardio-metabolic risk factors, including visceral obesity, dyslipidemia, hyperglycemia with insulin resistance, and hypertension. As there is a close link between MetS and cardiovascular diseases, we aimed to investigate the sex-based differences in MetS-associated heart failure (HF) and cardiovascular response to regular exercise training (ET).

Methods: High-fat diet-fed male and female APOB-100 transgenic (HFD/APOB-100, 3 months) mice were used as MetS models, and age- and sex-matched C57BL/6 wild-type mice on standard diet served as healthy controls (SD/WT).

Fundic gland polyps related to diverse aetiologies show subtle morphological differences: a multicentre retrospective study.

Aims: Fundic gland polyps (FGPs) comprise 66% of all gastric polyps. Although they are usually non-syndromic, they may be associated with various syndromes, including familial adenomatous polyposis (FAP) or gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS). We aimed to evaluate how histological features relate to distinct FGP subtypes.

Interobserver agreement of estimating the extent of intestinal metaplasia in patients with chronic atrophic gastritis.

The extent of gastric intestinal metaplasia (GIM) can be used to determine the risk of gastric cancer. Eleven international gastrointestinal expert pathologists estimated the extent of GIM on haematoxylin and eosin (H&E)- and Alcian blue-Periodic acid Schiff (AB-PAS)-stained slides of 46 antrum biopsies in 5% increments. Interobserver agreement was tested with the intraclass correlation coefficient (ICC).

Investigation of the Antihypertrophic and Antifibrotic Effects of Losartan in a Rat Model of Radiation-Induced Heart Disease.

Radiation-induced heart disease (RIHD) is a potential late side-effect of thoracic radiotherapy resulting in left ventricular hypertrophy (LVH) and fibrosis due to a complex pathomechanism leading to heart failure. Angiotensin-II receptor blockers (ARBs), including losartan, are frequently used to control heart failure of various etiologies. Preclinical evidence is lacking on the anti-remodeling effects of ARBs in RIHD, while the results of clinical studies are controversial.

Histologic Diagnosis of Inflammatory Bowel Diseases.

Inflammatory bowel disease, including ulcerative colitis and Crohn disease, is an idiopathic chronic inflammatory condition of the gastrointestinal tract. Since neither the clinical manifestations nor the morphologic features of inflammatory bowel disease are pathognomonic alone, the differential diagnosis to consider is relatively broad, and it relies on the synthesis of clinical, endoscopic, and microscopic features. Long-held histologic diagnostic principles include recognizing structural and inflammatory features of chronicity, that is, architectural distortion, basal plasmacytosis, and expansion of the lamina propria lymphoplasmacytic infiltrate.

Syntaxin-1 and Insulinoma-Associated Protein 1 Expression in Breast Neoplasms with Neuroendocrine Features.

A subset of breast neoplasia is characterized by features of neuroendocrine differentiation. Positivity for Neuroendocrine markers by immunohistochemistry is required for the diagnosis. Sensitivity and specificity of currently used markers are limited; based on the definitions of WHO Classification of Tumours, 5th edition, about 50% of breast tumors with features of neuroendocrine differentiation express chromogranin-A and 16% express synaptophysin.

Ischemic preconditioning protects the heart against ischemia-reperfusion injury in chronic kidney disease in both males and females.

Background: Uremic cardiomyopathy is a common cardiovascular complication of chronic kidney disease (CKD) characterized by left ventricular hypertrophy (LVH) and fibrosis enhancing the susceptibility of the heart to acute myocardial infarction. In the early stages of CKD, approximately 60% of patients are women. We aimed to investigate the influence of sex on the severity of uremic cardiomyopathy and the infarct size-limiting effect of ischemic preconditioning (IPRE) in experimental CKD.

Comparison of the antiremodeling effects of losartan and mirabegron in a rat model of uremic cardiomyopathy.

Uremic cardiomyopathy is characterized by diastolic dysfunction (DD), left ventricular hypertrophy (LVH), and fibrosis. Angiotensin-II plays a major role in the development of uremic cardiomyopathy via nitro-oxidative and inflammatory mechanisms. In heart failure, the beta-3 adrenergic receptor (β3-AR) is up-regulated and coupled to endothelial nitric oxide synthase (eNOS)-mediated pathways, exerting antiremodeling effects.

The Significance of Flat/Invisible Dysplasia and Nonconventional Dysplastic Subtypes in Inflammatory Bowel Disease: A Review of Their Morphologic, Clinicopathologic, and Molecular Characteristics.

Patients with inflammatory bowel disease are at significantly increased risk of dysplasia and colorectal cancer (CRC). The early detection, histologic grading, and removal of dysplasia plays a critical role in preventing the development of CRC. With advances in endoscopic visualization and resection techniques, colectomy is no longer recommended to manage dysplasia, unless surveillance colonoscopy detects flat/invisible dysplasia (either high-grade dysplasia or multifocal low-grade dysplasia) or an endoscopically unresectable lesion.

Upper Gastrointestinal Tract Involvement in Inflammatory Bowel Diseases: Histologic Clues and Pitfalls.

The upper gastrointestinal (UGI) manifestations of inflammatory bowel diseases (IBDs) are frequently obscured by classic ileal and colonic symptoms and are reported to involve only 0.5% to 4% of adult patients. However, because of the improvement of endoscopic techniques and the growing use of esophagogastroduodenososcopy with biopsy, both asymptomatic and clinically significant esophageal, gastric, and duodenal manifestations are increasingly recognized.

Comparative molecular subtypes of index and metachronous gastric adenocarcinomas: a study of 42 Korean patients.

To date, there have been no studies comparing the molecular subtypes of Index gastric cancers (IGCs) and metachronous gastric cancers (MGCs). We evaluated a cohort of 42 patients with 43 IGCs and 45 MGCs. Molecular subtyping was performed by immunohistochemistry of mismatch repair (MMR) proteins, E-cadherin, p53, and Epstein-Barr virus- (EBV-) in situ hybridization (ISH).

Nonampullary Duodenal Adenomas in Familial Adenomatous Polyposis and Sporadic Patients Lack the DNA Content Abnormality That Is Characteristic of the Adenoma-Carcinoma Sequence Involved in the Development of Other Gastrointestinal Malignancies.

Nonampullary duodenal adenomas (NADAs) develop sporadically or in the setting of a hereditary syndrome such as familial adenomatous polyposis (FAP). Although they are thought to progress into duodenal adenocarcinomas via an adenoma to carcinoma sequence similar to colorectal cancer, limited data suggested that they may be biologically dissimilar to colorectal adenomas. The clinicopathologic features of 71 patients diagnosed with NADAs (37 FAP and 34 sporadic) were analyzed.