A Role for the Vacuolating Cytotoxin, VacA, in Colonization and Helicobacter pylori-Induced Metaplasia in the Stomach

Carriage of Helicobacter pylori strains producing more active (s1/i1) forms of VacA is strongly associated with gas-tric adenocarcinoma. To our knowledge, we are the first to determine effects of different polymorphic forms of VacA on inflammation and metaplasia in the mouse stomach. Bacteria producing the less active s2/i2 form of VacA colonized mice more efficiently than mutants null for VacA or producing more active forms of it, providing the first evidence of a positive role for the minimally active s2/i2 toxin. Strains producing more active toxin forms induced more severe and extensive metaplasia and in flammation in the mouse stomach than strains producing weakly active (s2/i2) toxin. We also examined the association in humans, controlling for cag PAI status. In human gastric biopsy specimens, the vacA i1 allele was strongly associated with precancerous intestinal metaplasia, with almost complete absence of intestinal metaplasia in subjects infected with i2-type strains, even in a vacA s1, cagA+ background

Cartilaginous metaplasia of varicose veins: a case report

Cartilaginous metaplasia of superficial veins was found in a 64-year-old woman who underwent surgery for varicose veins. At operation, some varicose veins of the medial thigh were semi-rigid and fibroelastic to the touch. Histology revealed that half the lumen was occupied by chondroid tissue. The other half was obliterated by fibrous tissue, typical of post-thrombotic involution. Possible causes of cartilaginous metaplasia are briefly discussed

The pathologists’ eyes on foregut: histopathological relations in the experimental and routine diagnostics

SUMMARY I. The study aimed to investigate the incidence of duodeno-gastroesophageal reflux-induced malignoma formation in a series of duodeno-esophageal anastomosis operations in rats. This surgical method provided a model for the reflux-induced esophageal pathologies, without carcinogen administration. 30 weeks of duodeno-gastroesophageal reflux disease significantly increased the risk of the development of BE, and reflux-induced EAC formation was evident in 4 animals. In one of these particular cases, a superficial squamous cell cancer was noted in close vicinity to the adenocarcinoma formation. The results of the applied rat model afford evidence of the simultaneous activation of more than one possible carcinogenetic pathway in experimental GERD. Synchronous neoplasm formation with different growth pattern characteristics is a rarity in humans, and this phenomenon suggests that the presented model is a suitable means of mimicking the whole spectrum of human GERD pathology. II/1. The study aimed to carry out standardized histopathological analysis focusing not only on SIM but also on the presence of additional glands in the metaplastic process at 826 consecutive patients. According to standardized histopathological dataset the cases were classified and recorded by computerized method. The obtained data proved that 1) pure SIM is very rare in the Hungarian population, 2) cardiac and superficial mucous glands are good predictors for SIM, 3) pancreatic acinar and fundic metaplasias carry less severe metaplastic process, and 4) superficial mucous glands can be responsible for creating foregut-derived tissues and thus can be the origin of BE. II/2. The study aimed to assess the value of forceps biopsy sampling in establishing the correct diagnosis revealed by EMR as well as to evaluate the efficacy of this method. Fifty-six subjects with sessile gastric polyps of epithelial origin, at least 0.5 cm in diameter, and not associated with polyposis syndromes, were included. The obtained data showed that forceps biopsy is not fully representative of the entire lesion, and a simple biopsy may therefore lead to a faulty differentiation between the neoplastic and non-neoplastic lesions. EMR proposes diagnostic and staging advantage in assessing patients with EGC as compared to forceps biopsy, because it provides more intact mucosa and submucosa for histological analysis. Sessile gastric polyps should be fully resected by EMR for a final diagnosis and (depending on the lesion size and type) possibly definitive treatment

Interleukin-17A promotes parietal cell atrophy by inducing apoptosis

Background & Aims: Atrophic gastritis caused by chronic inflammation in the gastric mucosa leads to the loss of gastric glandular cells, including acid-secreting parietal cells. Parietal cell atrophy in a setting of chronic inflammation induces spasmolytic polypeptide expressing metaplasia, a critical step in gastric carcinogenesis. However, the mechanisms by which inflammation causes parietal cell atrophy and spasmolytic polypeptide expressing metaplasia are not well defined. We investigated the role of interleukin-17A (IL-17A) in causing parietal cell atrophy. Methods: A mouse model of autoimmune atrophic gastritis was used to examine IL-17A production during early and late stages of disease. Organoids derived from corpus glands were used to determine the direct effects of IL-17A on gastric epithelial cells. Immunofluorescent staining was used to examine IL-17A receptors and the direct effect of signaling on parietal cells. Mice were infected with an IL-17A-producing adenovirus to determine the effects of IL-17A on parietal cells in vivo. Finally, IL-17A neutralizing antibodies were administered to mice with active atrophic gastritis to evaluate the effects on parietal cell atrophy and metaplasia. Results: Increased IL-17A correlated with disease severity in mice with chronic atrophic gastritis. IL-17A caused caspase-dependent gastric organoid degeneration, which could not be rescued with a necroptosis inhibitor. Parietal cells expressed IL-17A receptors and IL-17A treatment induced apoptosis in parietal cells. Overexpressing IL-17A in vivo induced caspase-3 activation and terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling staining in parietal cells. Finally, IL-17A neutralizing antibody decreased parietal cell atrophy and metaplasia in mice with chronic atrophic gastritis. Conclusions: These data identify IL-17A as a cytokine that promotes parietal cell apoptosis during atrophic gastritis, a precursor lesion for gastric cancer. Keywords: IL-17A, Atrophy, Metaplasia, Apoptosi

Treatment of helicobacter pylori infection in atrophic gastritis

Helicobacter pylori (Hp) is a major human pathogen causing chronic, progressive gastric mucosal damage and is linked to gastric atrophy and cancer. Hp-positive individuals constitute the major reservoir for transmission of infection. There is no ideal treatment for Hp. Hp infection is not cured by a single antibiotic, and sometimes, a combined treatment with three or more antibiotics is ineffective. Atrophic gastritis (AG) is a chronic disease whose main features are atrophy and/or intestinal metaplasia of the gastric glands, which arise from long-standing Hp infection. AG is reportedly linked to an increased risk for gastric cancer, particularly when extensive intestinal metaplasia is present. Active or past Hp infection may be detected by conventional methods in about two-thirds of AG patients. By immunoblotting of sera against Hp whole-cell protein lysates, a previous exposure to Hp infection is detected in all AG patients. According to guidelines, AG patients with Hp positivity should receive eradication treatment. The goals of treatment are as follows: (1) Cure of infection, resolution of inflammation and normalization of gastric functions; (2) possible reversal of atrophic and metaplastic changes of the gastric mucosa; and (3) prevention of gastric cancer. An ideal antibiotic regimen for Hp should achieve eradication rates of approximately 90%, and complex multidrug regimens are required to reach this goal. Amongst the factors associated with treatment failure are high bacterial load, high gastric acidity, Hp strain, smoking, low compliance, overweight, and increasing antibiotic resistance. AG, when involving the corporal mucosa, is linked to reduced gastric acid secretion. At a non-acidic intra-gastric pH, the efficacy of the common treatment regimens combining proton pump inhibitors with one or more antibiotics may not be the same as that observed in patients with Hp gastritis in an acid-producing stomach. Although the efficacy of these therapeutic regimens has been thoroughly tested in subjects with Hp infection, there is a paucity of evidence in the subgroup of patients with AG. Bismuth-based therapy may be an attractive treatment in the specific setting of AG, and specific studies on the efficacy of bismuth-based therapies are needed in patients with AG

Immunophenotype of Atypical Polypoid Adenomyoma of the Uterus: Diagnostic Value and Insight on Pathogenesis

Atypical polypoid adenomyoma (APA) is a rare uterine lesion constituted by atypical endometrioid glands, squamous morules, and myofibromatous stroma. We aimed to assess the immunophenotype of the 3 components of APA, with regard to its pathogenesis and its differential diagnosis. A systematic review was performed by searching electronic databases from their inception to January 2019 for immunohistochemical studies of APA. Thirteen studies with 145 APA cases were included. APA glands appeared analogous to atypical endometrial hyperplasia (endometrioid cytokeratins pattern, Ki67≤50%, common PTEN loss, and occasional mismatch repair deficiency); the prominent expression of hormone receptors and nuclear β-catenin suggest that APA may be a precursor of "copy number-low," CTNNB1-mutant endometrial cancers. Morules appeared as a peculiar type of hyperdifferentiation (low KI67, nuclear β-catenin+, CD10+, CDX2+, SATB2+, p63-, and p40-), analogous to morular metaplasia in other lesions and distinguishable immunohistochemically from both conventional squamous metaplasia and solid cancer growth. Stroma immunphenotype (low Ki67, α-smooth-muscle-actin+, h-caldesmon-, CD10-, or weak and patchy) suggested a derivation from a metaplasia of normal endometrial stroma. It was similar to that of nonatypical adenomyoma, and different from adenosarcoma (Ki67 increase and CD10+ in periglandular stroma) and myoinvasive endometrioid carcinoma (h-caldesmon+ in myometrium and periglandular fringe-like CD10 pattern)

Recurrence of intestinal metaplasia and early neoplasia after endoscopic eradication therapy for Barrett’s esophagus: A systematic review and meta-analysis

Abstract Background Conflicting data exist with regard to recurrence rates of intestinal metaplasia (IM) and dysplasia after achieving complete eradication of intestinal metaplasia (CE-IM) in Barrett’s esophagus (BE) patients. Aim (i) To determine the incidence of recurrent IM and dysplasia achieving CE-IM and (ii) to compare recurrence rates between treatment modalities [radiofrequency ablation (RFA) with or without endoscopic mucosal resection (EMR) vs stepwise complete EMR (SRER)]. Methods A systematic search was performed for studies reporting on outcomes and estimates of recurrence rates after achieving CE-IM. Pooled incidence [per 100-patient-years (PY)] and risk ratios with 95 %CI were obtained. Heterogeneity was measured using the I 2 statistic. Subgroup analyses, decided a priori, were performed to explore heterogeneity in results. Results A total of 39 studies were identified (25-RFA, 13-SRER, and 2 combined). The pooled incidence of any recurrence was 7.5 (95 %CI 6.1 – 9.0)/100 PY with a pooled incidence of IM recurrence rate of 4.8 (95 %CI 3.8 – 5.9)/100 PY, and dysplasia recurrence rate of 2.0 (95 %CI 1.5 – 2.5)/100 PY. Compared to the SRER group, the RFA group had significantly higher overall [8.6 (6.7 – 10.5)/100 PY vs. 5.1 (3.1 – 7)/100 PY, P = 0.01] and IM recurrence rates [5.8 (4.3 – 7.3)/100 PY vs. 3.1 (1.7 – 4)/100 PY, P &lt; 0.01] with no difference in recurrence rates of dysplasia. Significant heterogeneity between studies was identified. The majority of recurrences were amenable to repeat endoscopic eradication therapy (EET). Conclusion The results of this study demonstrate that the incidence rates of overall, IM, and dysplasia recurrence rates post-EET are not inconsiderable and reinforce the importance of close surveillance after achieving CE-IM.</jats:p

The staging of gastritis with the olga system in the italian setting. histological features and gastric cancer risk

BACKGROUND: Recently OLGA (Operative Link on Gastritis Assessment) classification has been proposed to identify high-risk forms of gastritis that can evolve in gastric cancer (stages III and IV). Helicobacter pylori infection and age older than 40 have been considered as independent risk factor for high-risk OLGA stages

Frequency of gall bladder metaplasia and its distribution in different regions of gall bladder in routine cholecystectomy specimens

Background: In India, gall stone disease is more common in women in the north, north east and east as compared to other zones in the country. Gall bladder metaplasia has been documented as the precursor lesion of dysplasia and therefore carcinoma. Present study was conducted to ascertain the frequency and type of metaplasia along with distribution in different regions of gall bladder.Methods: All the post cholecystectomy gallbladder samples submitted for histopathology comprised the study material. Three sections were from body, fundus, and neck each. The five microns thick paraffin sections were cut with microtome and stained with Hemotoxylin and Eosin (H and E).Results: The present study was conducted on 119 cholecystectomy specimens submitted for histopathological examination. Amongst premalignant lesions, cholecystitis with metaplasia was seen in 55 (46.2%) cases. Pyloric metaplasia without intestinal metaplasia was most common metaplasia (30.2%) followed by combined metaplasia (12.60%) and only intestinal metaplasia (3.36%). Out of 55 cases, fundus showed metaplasia in 47 followed by body (44) and neck (36).Conclusions: Very high frequency of metaplasias was observed (46.2%) in routine cholecystectomy specimen with pyloric metaplasia as the predominant type and intestinal metaplasia was accompanied with pyloric metaplasia in most of the cases. Metaplasia was found to be more or less equally distributed in different regions of gall bladder