The Place of Histochemical Stains for Differential Diagnosis in Duodenal Biopsies

The biopsy is the primary examination method in diagnosing duodenal pathologies and Gluten enteropathy that can cause symptoms such as gas, diarrhea, weight loss, anemia, osteoporosis. Allows monitoring of response to therapy. Histochemical studies are inevitable in specific findings such as reactive changes, giardia, subepithelial collagen thickening, fibrosis, and gastric metaplasia. We aimed to understand the contribution of histochemical applications to differential diagnosis and to show their superiority compared to hematoxylin-eosin sections in routine use by simultaneously making histomorphological evaluations on hematoxylin and eosin sections. This research is a retrospective study conducted in 2011, using the archives of Yüzüncü Yıl University, Faculty of Medicine, Department of Pathology, between 2001-2010. Ten normal, 50 Gluten enteropathy and 50 duodenitis samples; Along with histopathological examinations, we applied Masson Trichrome, Periodic acid-Schiff, Periodic acid-Schiff with diastasis, Periodic acid Schiff-Alcian Blue, High Iron Diamine-Alcian Blue. Chi-square, likelihood ratio tests, and SPSS (ver: 13) statistical package program used. We detected microscopic findings parallel to diagnostic criteria. While the number of goblet cells and intraepithelial neutrophils did not differ in the groups (P =0.176 and P=0.096), there was a significant variation in the intraepithelial lymphocyte count (P=0.010). The frequency of flattening and blunting of the villi, crypt hyperplasia, and Brunner gland hyperplasia were significant in gluten enteropathies (P=0.000). Conclusion We could not find any difference in specific pathologies associated with histochemical studies in our group, so hematoxylin-eosin sections are more valuable in the differential diagnosis.

Using Human Induced Pluripotent Stem Cell Derived Organoids to Identify New Pathologies in Patients with PDX1 Mutations

Two patients with mutations in PDX1 presented with pancreatic agenesis, chronic diarrhea and poor weight gain, the causes of which were not identified through routine clinical testing. We generated patient derived organoids as a novel diagnostic strategy and observed that PDX1188delC/188delC antral organoids convert to an intestinal phenotype, while intestinal organoids undergo gastric metaplasia with significant reduction in enteroendocrine cells. This prompted a re-examination of gastric and intestinal biopsies from both PDX1188delC/188delC patients, which recapitulated organoid phenotypes. Antral biopsies had increased parietal cells and lacked G-cells suggesting loss of antral identity. These patients will now be monitored for the progression of metaplasia. This study demonstrates the utility of organoids for patient diagnoses and treatment.

Manifold role of ubiquitin in Helicobacter pylori infection and gastric cancer

Infection with H. pylori induces a strong host cellular response represented by induction of a set of molecular signaling pathways, expression of proinflammatory cytokines and changes in proliferation. Chronic infection and inflammation accompanied by secretory dysfunction can result in the development of gastric metaplasia and gastric cancer. Currently, it has been determined that the regulation of many cellular processes involves ubiquitinylation of molecular effectors. The binding of ubiquitin allows the substrate to undergo a change in function, to interact within multimolecular signaling complexes and/or to be degraded. Dysregulation of the ubiquitinylation machinery contributes to several pathologies, including cancer. It is not understood in detail how H. pylori impacts the ubiquitinylation of host substrate proteins. The aim of this review is to summarize the existing literature in this field, with an emphasis on the role of E3 ubiquitin ligases in host cell homeodynamics, gastric pathophysiology and gastric cancer.

Gastric metaplasia of the duodenal mucosa in Crohn’s disease: novel histological and endoscopic findings

Background and study aims Upper gastrointestinal endoscopy and biopsy are useful for differential diagnosis of Crohn’s disease (CD) of the large intestine and ulcerative colitis (UC). We aimed to identify novel histopathological and endoscopic findings in the upper gastrointestinal tract in patients with CD who did not have Helicobacter pylori infection. Patients and methods Upper gastrointestinal endoscopy was performed on patients with CD and UC. Mucosal lesions detected were subsequently observed using magnifying endoscopy with narrow-band imaging (M-NBI), following which biopsy was performed. When no mucosal lesion was detected on conventional endoscopy, M-NBI and biopsy were performed on four sites: the gastric body, gastric antrum, duodenal bulb, and second portion of the duodenum. Results The prevalences of gastric metaplasia (GM) were 48 % (24/50) and 16 % (8/50) in the CD and UC groups, showing a significant difference (P = 0.001). In 23 of 24 patients with histologically proven GM in the CD group, mucosal lesions were detected using conventional white-light imaging (C-WLI). In 22 of 24 patients with histologically proven GM in the CD group, disappearance of normal villous structure and the presence of curved marginal crypt epithelium were noted using magnifying endoscopic findings characteristic of GM (M-GM). A combination of C-WLI and M-NBI yielded a significantly increased specificity (P = 0.004) and accuracy (P = 0.039). Conclusions The prevalence of GM in the duodenal mucosa was significantly higher in patients with CD than in controls. The identified endoscopic findings may be useful as novel indicators for the histological diagnosis of GM in the duodenum.

Tristetraprolin prevents gastric metaplasia in mice by suppressing pathogenic inflammation

Aberrant immune activation is associated with numerous inflammatory and autoimmune diseases and contributes to cancer development and progression. Within the stomach, inflammation drives a well-established sequence from gastritis to metaplasia, eventually resulting in adenocarcinoma. Unfortunately, the processes that regulate gastric inflammation and prevent carcinogenesis remain unknown. Tristetraprolin (TTP) is an RNA-binding protein that promotes the turnover of numerous pro-inflammatory and oncogenic mRNAs. Here, we utilized a TTP-overexpressing model, the TTPΔARE mouse, to examine whether TTP can protect the stomach from adrenalectomy (ADX)-induced gastric inflammation and spasmolytic polypeptide-expressing metaplasia (SPEM). We found that TTPΔARE mice were completely protected from ADX-induced gastric inflammation and SPEM. RNA sequencing revealed that TTP overexpression suppressed the expression of genes associated with the innate immune response. Finally, we show that protection from gastric inflammation was only partially due to suppression of Tnf, a well-known TTP target. Our results demonstrate that TTP exerts broad anti-inflammatory effects in the stomach and suggest that therapies that increase TTP expression may be effective treatments of pro-neoplastic gastric inflammation.