Methylene blue (MB) is used endoscopically to demarcate tumors and as a photosensitizer in photodynamic therapy (PDT). However, there are few in vivo studies about its toxicity in healthy stomach tissue. We performed sequential in vitro and in vivo analyses of MB-induced phototoxicity.

We performed in vitro experiments using the AGS human gastric cancer cell line treated with light-emitting diode (LED) irradiation (3.6 J/cm2) and MB. Cytotoxicity was evaluated using terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. In vivo toxicity was evaluated in the stomach of beagles using the same dose of fiber-optic LED via gastroscopy, after spraying 0.1% and 0.5% MB solutions. Stomach tissue was also evaluated using the TUNEL assay.

In vitro, increased concentrations of MB led to higher TUNEL scores. However, cell viability was significantly lower after MB plus LED irradiation than after treatment with MB alone (P < 0.001). In vivo, the TUNEL score was highest immediately after treatment with 0.1% or 0.5% MB plus light irradiation, and the score was significantly higher in the LED illumination plus MB group than in the control group (P < 0.05). The elevated TUNEL score was maintained for 3 days in the MB plus light irradiation group but returned to normal levels on day 10.

: Endoscopic light application with MB 0.5% concentration to the stomach may be regarded as a safe procedure despite some DNA injuries in the early period.

The human stomach functions as both a digestive and innate immune organ. Its main product, acid, rapidly breaks down ingested products and equally serves as a highly effective microbial filter. The gastric epithelium has evolved mechanisms to appropriately handle the myriad of injurious substances, both exogenous and endogenous, to maintain the epithelial barrier and restore homeostasis. The most significant chronic insult that the stomach must face is Helicobacter pylori (Hp), a stomach-adapted bacterium that can colonize the stomach and induce chronic inflammatory and pre-neoplastic changes. The progression from chronic inflammation to dysplasia relies on the decades-long interplay between this oncobacterium and its gastric host. This review summarizes the functional and molecular regionalization of the stomach at homeostasis and details how chronic inflammation can lead to characteristic alterations in these developmental demarcations, both at the topographic and glandular levels. More importantly, this review illustrates our current understanding of the epithelial mechanisms that underlie the pre-malignant gastric landscape, how Hp adapts to and exploits these changes, and the clinical implications of identifying these changes in order to stratify patients at risk of developing gastric cancer, a leading cause of cancer-related deaths worldwide.

Pyloric gland metaplasia (PGM) is a histopathologic change usually seen after inflammatory injury and, although described in association with inflammatory bowel disease (IBD) and particularly Crohn disease (CD), its significance is still debated. We evaluated long-term correlates of PGM in a large cohort of 601 intestinal specimens, 227 (37.8%) biopsies, and 374 (62.2%) resections, from 567 different patients, 328 (57.8%) male and 239 (42.2%) female, with a mean age of 43.4±15.8 years. During mean clinical follow-up of 83.5±48.1 months, 511 (90.1%) patients were diagnosed with IBD, 457 (89.4%) with CD, and 53 (10.4%) with ulcerative colitis. In multivariate analysis, IBD patients with PGM were younger (P<0.001) and more often had severely active inflammation (P=0.002) compared with non-IBD patients, whereas, among IBD patients, those with ulcerative colitis were more likely to have PGM in a biopsy (P<0.001) or in the colorectum (P=0.009), compared with CD patients. Kaplan-Meier analyses showed that incidental PGM in a biopsy was more likely to predict IBD in patients younger than 50 years (P<0.001) and those without a history of bowel surgery (P<0.001) and also more likely to signify CD in patients younger than 50 years (P=0.004), those without a history of bowel surgery (P=0.020), and when identified in the small intestine (P=0.032). In conclusion, intestinal PGM warrants a high suspicion for IBD and specifically CD, however, it should be interpreted with caution, especially in older patients or those with a history of prior intestinal surgery and in colorectal biopsies or specimens lacking severely active inflammation.

The gastrointestinal mucosae provide a critical barrier between the external and internal milieu. Thus, damage to the mucosa requires an immediate response to provide appropriate wound closure and healing. Metaplastic lineages with phenotypes similar to the mucous glands of the distal stomach or Brunner's glands have been associated with various injurious scenarios in the stomach, small bowel, and colon. These lineages have been assigned various names including pyloric metaplasia, pseudopyloric metaplasia, ulcer-associated cell lineage (UACL), and spasmolytic polypeptide-expressing metaplasia (SPEM). A re-examination of the literature on these various forms of mucous cell metaplasia suggests that pyloric-type mucosal gland lineages may provide a ubiquitous response to mucosal injury throughout the gastrointestinal tract as well as in the pancreas, esophagus, and other mucosal surfaces. While the cellular origin of these putative reparative lineages likely varies in different regions of the gut, their final phenotypes may converge on a pyloric-type gland dedicated to mucous secretion. In addition to their healing properties in the setting of acute injury, these pyloric-type lineages may also represent precursors to neoplastic transitions in the face of chronic inflammatory influences. Further investigations are needed to determine how discrete molecular profiles relate to the origin and function of pyloric-type metaplasias previously described by histological characteristics in multiple epithelial mucosal systems in the setting of acute and chronic damage. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Gastric metaplasia (GM) of the duodenum is difficult to assess because of its patchy distribution, and the role of GM in functional dyspepsia (FD) is not clear. The aims of this study were to determine if endomicroscopy could identify GM of the duodenum and whether GM has associations with FD.

A series of 51 patients with FD and 25 asymptomatic controls were enrolled. Confocal laser endomicroscopy was performed to evaluate villi changes in vivo. Targeted biopsy specimens were then compared with histopathological results.

The accuracy of the endomicroscopy diagnosis of GM during endoscopy was 92.8%, and the sensitivity, specificity, and positive and negative predictive values were 86.2%, 97.4%, 89.3%, and 96.6%, respectively. The mean κ-value for interobserver agreement was 0.89. GM in the duodenal bulb was more frequent in patients with FD than in the controls (33.3% vs 12%, P<0.05), especially in patients with epigastric pain syndrome (47.6% vs 12%, P<0.01).

Endomicroscopy is useful for identifying GM, and GM might be related to FD. These findings could have potential applicability for duodenal screening, and suggest a possible targeting therapy in FD.

To investigate the correlation among the presence and degree of gastric metaplasia of duodenal regenerating mucosa, the deformity of bulb and the recurrence of duodenal ulcer.

A total of 99 patients with duodenal ulcer were treated with H(2)-antagonist with or without antimicrobial therapy. All patients received follow-up endoscopic examinations 6 wk after treatment. When the ulcer(s) were noted to be healed, two biopsies were taken from the ulcer scar for histological study of gastric metaplasia, and 4 biopsies were taken from antrum for Helicobacter pylori (H pylori) study. Out of these cases, 44 received further follow-up endoscopic examinations after 3, 6 and 12 mo respectively for studying the recurrence rate of duodenal ulcers. The correlation among ulcer recurrence, degree of gastric metaplasia of regenerating mucosa, bulbar deformity, and colonization of H pylori in the stomach was then studied.

The results showed that there was a strong correlation between the deformity of duodenal bulb and the degree of gastric metaplasia of regenerating duodenal mucosa. The recurrence rate of duodenal ulcer had a significant difference between patients with and without H pylori colonization in the stomach (P<0.001). The greater the degree of gastric metaplasia of duodenal regenerating mucosa, the higher the recurrence rate of duodenal ulcer (P = 0.021). The more deformed the duodenal bulb, the higher the incidence of recurrence of duodenal ulcer (P = 0.03).

There is a correlation among deformity of duodenal bulb, gastric metaplasia of duodenal regenerating mucosa and recurrence of duodenal ulcer. A more severely deformed duodenal bulb is closely related to a greater extent of gastric metaplasia. Both factors contribute to the recurrence of duodenal ulcer.

Previous reports, based on surgery, showed duodenal ulcer (DU) to be more common in the rice-eating areas of southern India than in the northern wheat-eating areas.

Does this difference persist? Can it be explained by risk factors other than diet?

A total of 20 053 records from patients undergoing endoscopy for dyspepsia, and 590 endoscopy patients from two northern and two southern centers in India were studied prospectively. Records were scrutinized to determine the relative incidence of DU and non-ulcer dyspepsia in wheat- and rice-eating areas. Age, sex, length of history, smoking and medication were recorded. Three antral biopsies and one from each duodenal quadrant were taken. A rapid urease test was carried out on one of the antral biopsies; the others were examined for Helicobacter pylori, gastritis, duodenitis and duodenal gastric metaplasia.

The difference in diet-associated prevalence persisted. No differences in smoking, Helicobacter pylori infection or duodenal gastric metaplasia were found between the two regions, but all three were more common in DU than in non-ulcer dyspeptic patients from both dietary areas.

The dietary differences between the regions remain the only factor to account for the differences in DU prevalence. A strong interrelationship between duodenal gastric metaplasia and cigarette smoking is demonstrated.