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Endoscopic observation of squamous metaplasia of the stomach: a report of two cases.

Squamous metaplasia of the stomach is a rare clinical entity that occurs during healing of gastric ulcers or chronic inflammation. We have treated two patients with this condition, which has only occasionally been observed endoscopically. The first was a 60-year-old woman who initially presented with multiple gastric ulcers. Two months after treatment, a white patch about 4 cm in diameter was found in the lesser curvature of the cardiac region of stomach. The second patient was a 65-year-old woman, who also developed a white patch in the same region. Two months later, a small ulcer and inflamed mucosa were seen near the lesion. The white areas in both patients were stained with Lugol's iodine solution, and biopsy specimens confirmed squamous epithelium. The squamous metaplasia was observed as a white mucosal area in the stomach, and the metaplastic area stained positively with Lugol's iodine solution.

Aged↗

[Early duodenal adenocarcinoma arising in gastric metaplasia treated by endoscopic resection].

Early duodenal carcinoma is a rare entity. Most duodenal carcinomas are diagnosed at a more advanced stage. This report describes the case of a 59-year-old lady with an early duodenal adenocarcinoma diagnosed at check-up gastroduodenoscopy in an outpatient clinic who was referred to us for further investigation and management. The initial upper endoscopy at our department revealed a type IIa+c lesion in the proximal duodenum (10 - 12 mm diameter, flat elevated lesion with central depression). Using chromoendoscopy and magnification endoscopy the lesion could be well demarcated and neoplastic changes in the architecture of the intestinal villi could be detected. After submucosal epinephrine-saline injection, the lesion was removed by endoscopic resection without complications. Histopathological examination revealed the rare entity of an early duodenal carcinoma arising from incomplete-type gastric metaplasia in the duodenum. In summary, the presented paper describes a case of successful endoscopic treatment of an early duodenal carcinoma arising from incomplete gastric metaplasia.

Adenocarcinoma↗

Non-biopsy detection of intestinal metaplasia and dysplasia in Barrett's esophagus: a prospective multicenter study.

BACKGROUND AND STUDY AIMS: There have been no multicenter studies investigating the use of magnification chromoendoscopy (MCE) for the detection of intestinal metaplasia and dysplasia/cancer in Barrett's esophagus. Our aims were to assess the ability of MCE to predict the histological diagnosis (non-biopsy detection), to compare the yield of MCE-targeted versus random biopsies for dysplasia, and to compare procedure times. PATIENTS AND METHODS: In this prospective multicenter study, patients with known or suspected Barrett's esophagus underwent MCE with indigo carmine dye staining. Three mucosal patterns (ridge/villous, circular, and irregular/distorted) were standardized, based on past experience. Mucosal patterns were noted and target biopsies were obtained only if irregular/distorted patterns were identified. Otherwise, random four-quadrant biopsies were obtained. RESULTS: A total of 56 patients (mean age 64 years, mean length of Barrett's esophagus 2.7cm) were prospectively evaluated: 38 patients (67.8 %) had ridge/villous patterns, four patients (7.1 %) had circular patterns, four patients (7.1 %) had irregular/distorted patterns, and ten patients (17.8 %) had a combination of patterns. Histologically, intestinal metaplasia was not shown in eight patients (14.2 %), nondysplastic Barrett's esophagus was diagnosed in 30 patients (53.5 %), low-grade dysplasia was detected in 12 patients (21.4 %), and high-grade dysplasia was detected in six patients (10.7 %). An irregular/distorted pattern either throughout the entire segment of Barrett's esophagus or in combination with a ridge/villous or circular pattern had a sensitivity or 83 %, a specificity of 88 %, a positive predictive value of 45 %, and a negative predictive value of 98 % for high-grade dysplasia. The yield of high-grade dysplasia was similar for the two techniques but the time taken to perform MCE was less than the time taken to perform random biopsies. CONCLUSION: An irregular/distorted pattern is specific for high-grade dysplasia and so it may not be necessary to perform biopsies in patients with ridge/villous or circular mucosal patterns.

Adult↗

Atrophic gastritis and intestinal metaplasia in asymptomatic Hungarian and Italian populations.

The histological patterns of the gastric mucosa obtained by endoscopic biopsy were evaluated in two different ethnic groups, each containing one hundred patients without gastro-intestinal diseases. The incidence of atrophic gastritis and intestinal metaplasia increased with age in both groups, revealing a statistically significant difference above 60 years. The comparative study of gastric cancer death rates in the two population groups showed a significant prevalence in the Hungarians above 50 years. This fact seems to support the hypothesis that an ethnic group with high gastric cancer rate has a higher prevalence of atrophic gastritis and intestinal metaplasia in the older age groups, and offers additional evidence for the association of chronic inflammatory changes of the gastric mucosa with malignant gastric cancer.

Adult↗

Stomachs of mice lacking the gastric H,K-ATPase alpha -subunit have achlorhydria, abnormal parietal cells, and ciliated metaplasia.

The H,K-ATPase of the gastric parietal cell is the most critical component of the ion transport system mediating acid secretion in the stomach. To study the requirement of this enzyme in the development, maintenance, and function of the gastric mucosa, we used gene targeting to prepare mice lacking the alpha-subunit. Homozygous mutant (Atp4a(-/-)) mice appeared healthy and exhibited normal systemic electrolyte and acid-base status but were achlorhydric and hypergastrinemic. Immunocytochemical, histological, and ultrastructural analyses of Atp4a(-/-) stomachs revealed the presence of chief cells, demonstrating that the lack of acid secretion does not interfere with their differentiation. Parietal cells were also present in normal numbers, and despite the absence of alpha-subunit mRNA and protein, the beta-subunit was expressed. However, Atp4a(-/-) parietal cells had dilated canaliculi and lacked typical canalicular microvilli and tubulovesicles, and subsets of these cells contained abnormal mitochondria and/or massive glycogen stores. Stomachs of adult Atp4a(-/-) mice exhibited metaplasia, which included the presence of ciliated cells. We conclude that ablation of the H,K-ATPase alpha-subunit causes achlorhydria and hypergastrinemia, severe perturbations in the secretory membranes of the parietal cell, and metaplasia of the gastric mucosa; however, the absence of the pump appears not to perturb parietal cell viability or chief cell differentiation.

Achlorhydria↗

Helicobacter-induced intestinal metaplasia in the stomach correlates with Elk-1 and serum response factor induction of villin.

Chronic Helicobacter pylori infection results in serious sequelae, including atrophy, intestinal metaplasia, and gastric cancer. Intestinal metaplasia in the stomach is defined by the presence of intestine-like cells expressing enterocyte-specific markers, such as villin. In this study, we demonstrate that villin is expressed in intestine-like cells that develop after chronic infection with H. pylori in both human stomach and in a mouse model. Transfection studies were used to identify specific regions of the villin promoter that are inducible by exposure of the cells to H. pylori. We demonstrated that induction of the villin promoter by H. pylori in a human gastric adenocarcinoma cell line (AGS) required activation of the Erk pathway. Elk-1 and the serum response factor (SRF) are downstream transcriptional targets of the Erk pathway. We observed inducible binding of Elk-1 and the SRF after 3 and 24 h of treatment with H. pylori, suggesting that the bacteria alone are sufficient to initiate a cascade of signaling events responsible for villin expression. Thus, H. pylori induction of villin in the stomach correlates with activation and cooperative binding of Elk-1 and the SRF to the proximal promoter of villin.

Animals↗

Chronic cholecystitis with bone metaplasia. A case report.

Bone metaplasia is a rare phenomenon in the gastrointestinal tract. We present a case of a 58-year-old man who underwent laparoscopic cholecystectomy for symptoms of chronic cholecystitis. Histologic examination of the removed gallbladder revealed intramural bone metaplasia in association with chronic cholecystitis. To the best of our knowledge, such a case has not yet been reported. The clinical significance of this finding remains to be elucidated.

Cholecystectomy, Laparoscopic↗

Squamous cell metaplasia of the nasopharyngeal epithelium and its association with adult-onset otitis media with effusion.

CONCLUSION: The common association between adult-onset otitis media with effusion (AO-OME) and squamous cell metaplasia (SCM) of the epithelium of Rosenmüller's fossa, which is near the Eustachian tube orifice, implies the predictive role of metaplasia, which probably compromises the drainage function of the middle ear. OBJECTIVE: To determine the effects of nasopharyngeal epithelial changes (SCM) on AO-OME. AO-OME is a multifactorial and insidious disease that may necessitate detailed investigation, i.e. biopsy of the nasopharynx, because of possible underlying nasopharyngeal malignancy. MATERIAL AND METHODS: Fifty-two patients with AO-OME (study group) and 29 with a unilateral neck mass in the posterior triangle without AO-OME (control group) were enrolled. Nasopharyngeal biopsies taken from all subjects were evaluated with regard to surface epithelial changes of the nasopharynx. RESULTS: Nasopharyngeal biopsies revealed SCM in 34/52 patients (65%) in the study group and 9/29 (31%) in the control group (p<0.05). During the follow-up period, recurrence of effusion occurred in 56% of the group with SCM and 22% of the group without it.

Adolescent↗

Helicobacter pylori in areas of intestinal metaplasia in gastric antral mucosa.

Colonization of areas of intestinal metaplasia by Helicobacter pylori is rare and there is only one report in the literature of this organism colonizing areas of intestinal metaplasia in the antral mucosa. We report two more cases where H. pylori were seen in the gastric pits with intestinal metaplastic changes in the antral biopsy specimens.

Adolescent↗

Prevalence of precancerous and other metaplasia in the distal oesophagus and gastro-oesophageal junction.

OBJECTIVE: The epidemiology of Barrett's oesophagus (BO) is characterized by divergent results. The aim of this study was to estimate the prevalence of BO and intestinal metaplasia (IM) at the gastro-oesophageal junction (GOJ) in a population-based series of patients referred for first-time gastroscopy. MATERIAL AND METHODS: Consecutive patients who underwent endoscopy for the first time at endoscopy units exclusively serving defined catchment areas were invited to take part in the study. Biopsies were taken immediately below the GOJ and from the distal oesophagus, and clinical data were recorded. RESULTS: A total of 769 patients (mean age 53 years, 43% M) were examined. Overall IM prevalence was 14%. BO was noted in 4%. Overall, the prevalence of IM increased by 8% (95% CI 6-10%) per year of age. BO patients were predominately women (69%). Presence of cardia-type mucosa in the cardia increased with age from 25% among the youngest to 59% among the oldest patients. Pancreatic acinar metaplasia (PAM) was found in 18%. CONCLUSIONS: While BO is not common among Swedish gastroscopy patients, IM and PAM are found in every 7th and 6th patient, respectively. Age-dependent increments in prevalence suggest that not only BO and IM, but also cardia-type mucosa are acquired and/or progressive lesions.

Adolescent↗

Evaluation of sensitivity and inter- and intra-observer variability in the detection of intestinal metaplasia and dysplasia in Barrett's esophagus with enhanced magnification endoscopy.

OBJECTIVE: Magnification endoscopy with acetic acid or dye for diagnosis of Barrett's esophagus is presently undergoing clinical evaluation. Current studies report good accuracy in predicting specialized intestinal metaplasia. To date, however, there is no definitive information on the inter- and intra-observer variability of these methods applied to the diagnosis of normal and dysplastic Barrett's mucosa. MATERIAL AND METHODS: Sixty patients with endoscopically suspected Barrett's esophagus were investigated prospectively with the zoom endoscope after contrast enhancement of the mucosa with 1.5% acetic acid. Two hundred and twenty-three enlarged and histologically investigated areas of gastric, cardiac, normal and dysplastic Barrett's mucosa were photodocumented and in randomized sequence presented to 4 endoscopists in a blinded manner (2 with and 2 without experience of zoom endoscopy for evaluation). The reference for the first evaluation (A1) was standard endoscopic photographs of the respective, histologically confirmed mucosal entity. In a second evaluation (A2), the pictures were again interpreted by the same blinded investigators, but this time a modified pit-pattern classification as proposed by Sharma et al. was employed as the evaluation reference. RESULTS: The diagnostic sensitivity for specialized intestinal metaplasia and dysplasia in Barrett's esophagus calculated for the A1 evaluation ranged -- investigator dependently -- from 54.9% to 80.7% and for A2 from 42.2% to 81.5%. The inter- and intra-observer variability for the evaluation procedure A1 and A2 was high (all kappa values <0.4). In particular, the inexperienced investigators demonstrated high intra-observer variability and low sensitivity in comparison with the experienced investigators. CONCLUSIONS: The diagnosis of Barrett's mucosa using enhanced magnification endoscopy after acetic acid instillation is associated with a high level of interobserver variability. One reason is a frequent mismatch between cardiac mucosa and non-dysplastic Barrett's mucosa.

Adult↗

Novel subtyping of intestinal metaplasia in the human stomach: brain-type glycogen phosphorylase expression in the proliferative zone and its relationship with carcinogenesis.

Although reports have suggested the incomplete type of intestinal metaplasia (IM) had a close correlation with carcinoma, considerable data showed no apparent relationship between the particular type of IM and the intestinal type carcinoma. The purpose of this study was to establish a novel classification of IM using brain-type glycogen phosphorylase (BGP) from a carcinogenetic viewpoint. The only isoform expressed in gastric cancer was BGP using polymerase chain reaction analysis. We studied 136 specimens with gastric carcinoma and the adjacent IM using specific anti-BGP antibody with its correlation to subtypes of IM, proliferating cell nuclear antigen-labeling index, and various oncogene products. Brain-type glycogen phosphorylase was expressed in 80.5% of the intestinal type and 18.8% of the diffuse type of carcinoma and in 87.5% and 41.6% in the generative zone of IM adjacent to cancer foci, respectively, whereas no reactivity was observed in the normal gastric mucosa. The proportion of the positivity in the cancer and IM was significantly greater in the intestinal-type carcinoma than in the diffuse type. The expression of BGP in the generative cells of IM had no significant correlation with the conventional type of IM. Intestinal metaplasias with BGP expression were significantly higher in a proliferating state than in those without BGP, and some of them that were coexpressed accumulated p53 in the generative cells. The relationship between IM with BGP in the generative cells and intestinal-type carcinoma was apparently closer than the conventional subtype of IM and gastric cancer. Intestinal-type carcinoma might arise from some of these proliferating cells with BGP.

Gastric Mucosa↗

Mesothelial cysts of the spleen with squamous metaplasia.

Epidermoid cyst (metaplastic mesodermal cyst) is the most common true cyst of the spleen. The pathogenesis is unknown. The lesion is usually asymptomatic and has a characteristic gross morphology. Two splenic epidermoid cysts which were mesothelial-lined and showed focal squamous metaplasia were observed. Examination of one adult spleen and ten fetal spleens showed similar mesothelial linings of their capsules. It is believed that the epithelial-lined splenic cysts are the result of invagination of capsular surface mesothelium with subsequent cystic expansion and metaplastic changes. The use of the term "mesothelial cyst with squamous metaplasia" as a more accurate term than "epidermoid" or "metaplastic mesodermal cyst" is suggested.

Adolescent↗

Nephrogenic metaplasia of the ureter.

We present what, to our knowledge, is the first reported case of nephrogenic metaplasia of the ureter. Nephrogenic metaplasia involves the transitional epithelium of the urinary tract and results in the formation of epithelial tubules, which are histologically similar to renal tubules. Special stains demonstrated both intracellular and intraluminal mucin. Ultrastructurally, the lesion consisted of epithelial cells with sparse microvilli and a thick basal lamina. The criteria for diagnosis and differentiation from carcinoma are discussed.

Adenoma↗

Squamous metaplasia of the breast. An ultrastructural and immunologic evaluation.

Squamous metaplasia in the breast is rare. This case of an intracystic papilloma of the breast with prominent squamous change was found by electron microscopy and immunohistochemistry to contain evidence of squamous differentiation within myoepithelial cells. The findings suggest that squamous metaplasia of the breast may result from myoepithelial cell differentiation in a manner analogous to the development of squamous lesions in the cervix and salivary gland. The possible relationship of this finding to the development of squamous lesions of the breast is discussed.

Adult↗

Prevalence of gastric metaplasia, inflammation, and Campylobacter pylori in the duodenum of members of a normal population.

Mucosal biopsies were obtained from 116 asymptomatic volunteers (50% were male; mean age, 46 years; age range, 19-91 years) to study the prevalence of duodenal gastric metaplasia (GM) and its association with inflammation and Campylobacter pylori in a normal population. GM was identified in 25 subjects (22%). Eighty-three subjects (72%) had histologic duodenitis, but in only 10 did the infiltrate include neutrophils (grade 2 duodenitis). C. pylori was found in the stomach in 36 subjects (31%), all of whom had gastritis, but was not identified histologically in the duodenum. There were no significant differences between the overall frequency of duodenitis and either GM or antral C. pylori. Although the frequency of severe (grade 2) duodenitis was not significantly different between those with and those without GM, grade 2 duodenitis was found in 9 of 36 subjects with antral C. pylori but in only 1 of 80 without antral C. pylori (P less than 0.001). These findings suggest that gastric metaplasia is a common finding in the normal population and that grade 1 duodenitis is most likely clinically unimportant, whereas grade 2 duodenitis is usually associated with antral C. pylori.

Adult↗

Asbestos and benzo[a]pyrene act synergistically to induce squamous metaplasia and incorporation of [3H]thymidine in hamster tracheal epithelium.

When exposed to either crocidolite asbestos (single 1-h exposure to 0.4 mg/ml medium) or the polycyclic aromatic hydrocarbon, benzo[a]pyrene (BaP) (less than or equal to 2.5 micrograms/ml medium, 1x weekly for 4 weeks), the epithelium of hamster tracheal explants exhibits insignificant amounts of squamous metaplasia, an atypical lesion, in comparison to amounts observed in untreated tissues. Incorporation of [3H]thymidine, an indication of DNA synthesis by epithelial cells, likewise is unchanged. However, the extent of squamous metaplasia and numbers of labeled basal and suprabasal cells are increased substantially when BaP and asbestos are added in combination. These results suggest an important mechanism of co-carcinogenesis involving chemical and physical carcinogens and support epidemiologic observations documenting an increased risk of bronchogenic carcinoma in asbestos workers who smoke.

Animals↗

Heightened susceptibility to chronic gastritis, hyperplasia and metaplasia in Kcnq1 mutant mice.

Increased susceptibility to gastric cancer has been associated with a wide range of host genetic and environmental factors, including Helicobacter pylori infection. Helicobacter pylori infection is postulated to initiate a progression through atrophic gastritis, metaplasia and dysplasia to cancer, and has been associated with reduction of acid output and dysregulation of stomach mucins. Here, we present the characterization of two mouse lines carrying mutant alleles of the gene encoding the Kcnq1 potassium channel, which very rapidly establish chronic gastritis in a pathogen-exposed environment. These mice develop gastric hyperplasia, hypochlorhydria and mucin dysregulation independent of infection. Metaplasia, dysplasia and pre-malignant adenomatous hyperplasia of the stomach have been observed in these Kcnq1 mutant mice, also independent of infection. The data presented here suggest that Kcnq1 mutant mice can be used both as an efficient model for the development of atrophic gastritis after infection and to determine the processes during the later stages of progression to gastric cancer independent of infection. Thus, Kcnq1 mutant mice are a powerful new tool for investigating the connection between acid balance, Helicobacter infection and mucin disruption in the progression to gastric cancer.

Achlorhydria↗