Gastric Metaplasia Research Articles

Gluten Challenge Causes Exacerbation of Postural Orthostatic Tachycardia Syndrome in a Patient With Ehlers-Danlos Syndrome: A Case Report

Introduction: Postural orthostatic tachycardia syndrome (POTS) is a form of dysautonomia associated with tachycardia upon standing, caused by a variety of disorders including Ehlers-Danlos syndrome. POTS therapy includes increasing fluid and salt intake. Studies have shown that gluten sensitivity may play a role in neurological disorders, and gluten is felt to exacerbate symptoms (Figure 1). POTS syndrome has been associated with gluten intolerance and GERD as risk factors for dysautonomia. A 20-year-old female with history of IBS presented to the hospital with several months of dizziness, vertigo, and gait imbalance. She had been experiencing joint polyarthralgias for 2 years. She had a long history of gastrointestinal complaints with flares of diarrhea as frequent as 6 times per day. She started a nearly gluten-free diet and noted improvement in her symptoms. Working diagnosis included IBS-D and celiac disease, and she was started on a gluten challenge. She was admitted 1 month later for worsening neurological symptoms. Work-up included EEG, EMG, and MRI brain/spine that were unremarkable. EGD revealed non-specific chronic inflammatory infiltrate in the lamina propria and focal gastric metaplasia. Biopsies were negative for celiac disease. Serum tissue transglutaminase and gliadin antibodies were negative. Genetic work-up revealed Ehlers-Danlos syndrome. It is believed she has an IBS variant with gluten intolerance and dysautonomia as the source of her symptoms. She was started on a PPI and has remained on a gluten-restricted diet with significant dissipation of her symptoms. We present an interesting case of exacerbation of Ehlers-Danlos associated POTS with implementation of a gluten challenge. While many neurological manifestations are associated with celiac disease, to our knowledge, no reports have been published studying the association and mechanism behind gluten exacerbating POTS in patients without celiac disease. Perhaps these “gluten sensitive” patients may benefit from a gluten-free diet as primary management of their chronic neurological conditions.Figure 1: Depicts interaction between gluten sensitivity and autoimmune, inflammatory, and neurological conditions.

Cholesterolosis in routine histopathological examination after cholecystectomy: What should a surgeon behold in the reports?

Introduction: Cholecystectomy is one of the most common surgical procedures. Postoperative investigation of cholecystectomy specimen has a great value since histopathological reports may document some entities with significant clinical consequences. The aim of this study was to evaluate the association between cholesterolosis and the reports indicating some histopathological alterations in symptomatic cholecystitis. Methods: This paper is based on a retrospective study. Histopathological reports of 432 cholecystectomy specimens between January 2011 and June 2013 were reviewed. Three reports were excluded due to perioperative diagnosis of cancer. Reports of 429 cholecystectomy specimens of the acute and symptomatic chronic cholecystitis patients were analyzed. Standardization of the reporting was questioned. Age, gender, histopathological wall thickness of gallbladder, reporting rates of acute inflammation, cholesterolosis, polypoid lesions, epithelial hyperplasia, gastric or intestinal metaplasia, dysplasia and incidental cancer were investigated and compared between patients with and without cholesterolosis. Reported rates of histopathological findings were comparable between patients under and over 60 years old and patients with and without reported cholesterolosis. Results: Reported histopathological findings were presented as acute inflammation in 46 (10.7%), cholesterolosis in 79 (18.4%), gallbladder polypoid lesions in 7 (1.6%), epithelial hyperplasia in 16 (3.7%), metaplasia of any type in 34 (7.9%) of 429 patients. Dysplasia was excluded whereas one incidental gallbladder carcinoma was reported. Epithelial hyperplasia and metaplasia were found to be related to age. Gallbladder wall thickness was decreased with cholesterolosis. However, only a correlation between cholesterolosis and gender or metaplasia was noted. Conclusion: Recent study suggests that cholesterolosis is somehow associated with metaplasia. Thus, surgeons should carefully interpret the histopathology reports based on unusual or exceptional findings corresponding to the cholecystectomy specimens. Any abnormal finding in the reports should be investigated in terms of the progress of the pathology and also its clinical consequences.

Endoscopic alterations in a cohort of hemodialysis patients: a cross-sectional study.

IntroductionAlthough the association between chronic kidney disease and dyspepsia is widely known, it remains poorly investigated. Among the types of gastric inflammation that lead to symptoms, erosive antral gastritis is the most common form. A direct correlation between the urea serum levels and the time in hemodialysis with the onset of gastric metaplasia and dyspepsia can be observed. The aim of this study was to report the endoscopic alterations found in hemodialysis patients.MethodsThis is a cross-sectional study based on the medical records of 95 patients older than 18 years who were diagnosed with chronic kidney disease. The results of endoscopies performed up to 6 months before the beginning of the study were included.ResultsAmong the 95 studied patients, 56.84% were male, 60% were Caucasian, and 71.57% used proton pump inhibitors. The endoscopic alteration most frequently observed was erosive gastritis (77% of the cases); however, the frequency of the alteration that caused the symptoms was irrelevant. The antrum was the most common site of involvement (55.79%).ConclusionPatients with chronic kidney disease often show dyspeptic symptoms. Other abnormalities are common but are not correlated with such symptoms. In conclusion, this study identified the endoscopic alterations that are most often observed in hemodialysis patients; erosive and enanthematous gastritis were the most common forms observed.

Duodenal gastric heterotopia, sporadic or fundic gland polyp-associated, frequently carries β-catenin mutation.

Duodenal gastric heterotopia (DGH) is a benign asymptomatic condition assumed to be of congenital origin. Since DGH is often associated with fundic gland polyps (FGPs) that frequently carry a somatic β-catenin gene mutation, we examined whether DGH, either sporadic or FGP-associated, is attributable to alterations of the Wnt/β-catenin pathway. Genetic analysis revealed frequent somatic β-catenin gene mutations in DGH; some of which showed the same mutation pattern as coexisting FGPs. All missense mutations were confined to codons 32, 33, and 37. No such mutations were observed, however, in any of the specimens from focal gastric foveolar metaplasia (GFM). Therefore, DGH is not a mere congenital lesion due to aberrant migration of normal gastric mucosa or a simple reactive metaplasia after regenerative stimuli of the duodenal mucosa, but a distinct condition based upon molecular genetic changes in the Wnt/β-catenin pathway.

Effects of nonsteroidal anti-inflammatory meloxicam on stomach, kidney, and liver of rats.

Nonsteroidal anti-inflammatory (NSAI) drugs are the most commonly used group of drugs today. Increase in the use of standard NSAI for treating pain and inflammation was restricted by the fact that these drugs were proven to possibly cause gastrointestinal and renal toxicity. Meloxicam is a NSAI that has anti-inflammatory, analgesic, and antipyretic effects. This study aims to investigate the effects of meloxicam on stomach, kidney, and liver of rats under light microscopy level. Based on the light microscopic observations, mononuclear cell infiltration and pseudolobular formation was established in liver samples of animals in the experimental group. Metaplasia in surface and glandular epithelia and atrophy were observed in stomach samples. Glomerular stasis-related hypertrophy and focal interstitial nephritis were found in kidneys. It was concluded in this study that meloxicam might cause hepatotoxicity, nephrotoxicity, and gastric metaplasia in rats at a used dose and duration.

265 Hedgehog/Gli1 Signaling Regulates Phenotypic Changes in Myeloid Cells During Helicobacter-Induced SPEM (Gastric Metaplasia)

Introduction: Recently, it has been shown that cells expressing the glial marker GFAP can make enteric neurons, raising the possibility that enteric glia can function as enteric neural precursor cells (ENPC). However, it is not known whether all or only a sub-population of enteric glia are ENPC. Apart from glial markers, ENPC are also known to express Nestin and p75NTR. Hence, using a Nestin-GFP mouse, we studied whether ENPC, defined by the co-expression of Nestin and p75NTR, express glial cell markers and whether all enteric glial cells express these ENPC markers. Methods: Cells from the longitudinal muscle-myenteric plexus (LMMP) of Nestin-GFP mice were flow sorted into four populations based on expression of Nestin-GFP and p75NTR for clonal proliferation and differentiation assays. Differentiated cells were tested for the presence of neurons and glia using immunocytochemistry. In separate analyses, these four cell populations were analyzed by FACS for the presence, co-localization, and intensity of fluorescence of glial markers GFAP and S100B. Results: By clonal analyses, we observe that only cells that co-express Nestin and p75NTRHI proliferate (Mean ± S.E. of percentage proliferative cells: 10.2 ± 0.62) and differentiate to form neurons and glia (Mean ± S.E. of percentage of neurospheres that differentiate to neurons and glia: 78.26 ± 4.35). ENPC, defined now by Nestin-p75NTRHI co-expression, express the glial markers, GFAP and S100B. We observe that only 3.86% of enteric glial cells that co-express GFAP and S100B express Nestin-GFP and p75HI and hence qualify for ENPC. All other cells are presumably mature enteric glia. Discussion: We show that ENPC co-express Nestin and p75NTRHI apart from GFAP and S100B, confirming earlier results that ENPC express glial markers. However, ENPC only form a small fraction of the total enteric glial cells as only 3.86% of cells that co-express the glial markers express Nestin-GFP and p75NTRHI. Hence, ENPC either represent a sub-category of enteric glial cells or are non-glial cells expressing shared markers. Our data shows that not all enteric glia are ENPC. This work paves the way for understanding not only the true identity of ENPC, but also that of mature enteric glia.

Foveolar Gastric Metaplasia of the Duodenum: A Frequent, so far Neglected Type of Duodenal Polyp

Foveolar gastric metaplasia of the duodenum (FGM) is considered as imperfect mucosal healing in the context of H. pylori gastritis and intake of NSAIDs or ASS. Typical endoscopic findings are redness of the mucosa, erosion/ulcer and loss of mucosal folds. During diagnostic histological examinations we observed a frequent so far not described association of FGM with endoscopically observed duodenal polyps. The archives of two institutes of pathology with high gastroenterological workload (approximately 100 000 patients per year) were investigated for an association between "duodenal polyp" and "foveolar gastric metaplasia". In Institute 1, of 481 duodenal polyps 41 % were classified as FGM, 9 % as adenoma and 2 % as heterotopic gastric mucosa. In 48 % no histological correlate was present. In Institute 2, 217 cases of FGM were diagnosed. Of these, in 69 cases the endoscopic finding was "polyp" (32 %). In the other cases, the endoscopic findings were mucosal defect (18 %), redness/inflammation (16 %), suspicion for gastric heterotopia (5 %) and scar (3 %). In 26 % of cases no pathologic endoscopic finding was reported. Both groups of patients with FGM showed a similar distribution of age ranges (24 - 83 years and 16 - 88 years), median age (62 years and 61 years, respectively) and a dominance of male sex (both 1.5:1). In conclusion, foveolar gastric metaplasia is a frequent, so far neglected correlate of endoscopically detected duodenal polyps.

LIM homeodomain transcription factor Isl1 directs normal pyloric development by targeting Gata3

BackgroundAbnormalities in pyloric development or in contractile function of the pylorus cause reflux of duodenal contents into the stomach and increase the risk of gastric metaplasia and cancer. Abnormalities of the pyloric region are also linked to congenital defects such as the relatively common neonatal hypertrophic pyloric stenosis, and primary duodenogastric reflux. Therefore, understanding pyloric development is of great clinical relevance. Here, we investigated the role of the LIM homeodomain transcription factor Isl1 in pyloric development.ResultsExamination of Isl1 expression in developing mouse stomach by immunohistochemistry, whole mount in situ hybridization and real-time quantitative PCR demonstrated that Isl1 is highly expressed in developing mouse stomach, principally in the smooth muscle layer of the pylorus. Isl1 expression was also examined by immunofluorescence in human hypertrophic pyloric stenosis where the majority of smooth muscle cells were found to express Isl1. Isl1 function in embryonic stomach development was investigated utilizing a tamoxifen-inducible Isl1 knockout mouse model. Isl1 deficiency led to nearly complete absence of the pyloric outer longitudinal muscle layer at embryonic day 18.5, which is consistent with Gata3 null mouse phenotype. Chromatin immunoprecipitation, luciferase assays, and electrophoretic mobility shift assays revealed that Isl1 ensures normal pyloric development by directly targeting Gata3.ConclusionsThis study demonstrates that the Isl1-Gata3 transcription regulatory axis is essential for normal pyloric development. These findings are highly clinically relevant and may help to better understand pathways leading to pyloric disease.

Duodenal mucosal damage is associated with proliferative activity of Brunner’s gland hamartoma: a case report

BackgroundBrunner’s gland hamartoma is a rare tumor, predominantly found in the fifth to sixth decades of life. Generally, it is a single pedunculated polyp, rarely larger than 5 cm. Asymptomatic cases are found incidentally, but cases with a large polyp tend to have gastrointestinal bleeding and/or obstructive symptoms. Polyp size increases in a time-dependent manner, however, the growth mechanism is unknown. We report a Japanese male case in his mid-twenties with an over 6 cm sized polyp.Case presentationA 26-year-old man presented black stools and anemia. Endoscopic examination revealed a large pedunculated polyp at gastroduodenal junction. The polyp, subsequently resected by distal gastrectomy, was lobulated with random surface erosions and sized 6.4 × 3 cm. Histological examination revealed that the polyp arose from duodenal mucosa and was composed of hyperplastic Brunner’s glands in lobules separated by fibromuscular septa, associated with lymphocytic infiltrate and lymphoid follicles. No evidence of malignancy was found. Thus, the lesion was diagnosed as Brunner’s gland hamartoma. Further immunohistochemical studies indicated that gastric foveolar metaplasia is associated with surface epithelium covering upper two thirds of the polyp, showing immunohistochemical positivity for mucin 5 AC (MUC5AC). Below the metaplastic surface epithelium, Brunner’s glands had high proliferative activity (MIB-1 labeling index: 7.9%). The similar staining pattern was observed at surface erosive sites (MIB-1 labeling index in Brunner’s glands: 9%). On the other hand, surface epithelium in the lower side of the polyp still preserved intestinal nature, containing CDX2-positive nuclei and MUC2-positive goblet cells. Brunner’s glands below the surface epithelium with intestinal characteristics showed low proliferative activity (MIB-1 labeling index: 0.77%).ConclusionProliferative activity of Brunner’s glands was high at the sites with surface erosion and also below the epithelium showing gastric foveolar metaplasia. As gastric foveolar metaplasia occurs along with a mucosal repair process in the duodenum, mucosal damages underlay the hamartomatous proliferation of Brunner’s glands and eventually resulted in a formation of large polypoid mass in this case.

Giant Meckel’s diverticulum: An exceptional cause of intestinal obstruction

Meckel's diverticulum (MD) results from incomplete involution of the proximal portion of the vitelline (also known as the omphalomesenteric) duct during weeks 5-7 of foetal development. Although MD is the most commonly diagnosed congenital gastrointestinal anomaly, it is estimated to affect only 2% of the population worldwide. Most cases are asymptomatic, and diagnosis is often made following investigation of unexplained gastrointestinal bleeding, perforation, inflammation or obstruction that prompt clinic presentation. While MD range in size from 1-10 cm, cases of giant MD (≥ 5 cm) are relatively rare and associated with more severe forms of the complications, especially for obstruction. Herein, we report a case of giant MD with secondary small bowel obstruction in an adult male that was successfully managed by surgical resection and anastomosis created with endoscopic stapler device (80 mm, endo-GIA stapler). Patient was discharged on post-operative day 6 without any complications. Histopathologic examination indicated Meckel's diverticulitis without gastric or pancreatic metaplasia.

Histomorphology Spectrum of Gall Bladder Pathology in Cholecystectomy Specimens with Clinical Diagnosis of Chronic Cholecystitis

Chronic cholecystitis is a common disease in surgery where majority of cholecystectomy are performed. This study was carried out to see histomorphological pattern of gallbladder diseases, staining pattern with various stains and prevalence of carcinoma. This prospective study was conducted in the department of Pathology, B.P. Koirala Institute of Health Sciences, Dharan, Nepal from January to December 2008. A minimum of fifty random samples were included in study. Clinical details and pathological data were retrieved from case sheets and patient's history. All specimens were fixed in 10% formalin. Three sections each from neck, body and fundus were taken. Tissues were processed in an automated tissue processor and paraffin blocks made. The tissue sections were examined under light microscope after hematoxylin-eosin, neutral mucin, sulfated mucin and sialomucin stain. Chronic cholecystitis without cholelithiasis constituted majority of 25(50.0%) cases with M:F of 1:7.1. The gastric and intestinal metaplasias were present in 33.0% and 8.0% of the cases respectively. The neutral, sulfated and sailomucin were positive in 35.0%, 21.0%, 1.0% and 34.0%, 21.0%, 1.0% cases respectively in gastric and intestinal metaplasia. Both gastric and intestinal metaplasia showed significant p-value on sulfated mucin. The increase risk factors for developing of chronic cholecystitis were seen in female gender (86%). The gastric and intestinal metaplasia showed positivity more with neutral followed by sulfated mucin.

Qualitative analysis of anatomopathological changes of gastric mucosa due to long term therapy with proton pump inhibitors: experimental studies x clinical studies.

For a few decades the long-term use of proton pump inhibitors has had wide application in the treatment of several gastrointestinal diseases. Since then, however, several studies have called attention to the possible development of anatomical and pathological changes of gastric mucosa, resulting from the long term use of this therapeutic modality. Recent experimental and clinical studies suggest that these changes have connection not only to the development of precancerous lesions, but also of gastric tumors. To present a qualitative analysis of anatomical and pathological changes of gastric mucosa resulting from the long-term use of proton pump inhibitors. The headings used were: proton pump inhibitors, precancerous lesions and gastric neoplasms for a non systematic review of the literature, based on Medline, Lillacs and Scielo. Twelve articles were selected from clinical (9) and experimental (3) studies, for qualitative analysis of the results. The gastric acid suppression by high doses of proton pump inhibitors induces hypergastrinemia and the consequent emergence of neuroendocrine tumors in animal models. Morphological changes most often found in these experimental studies were: enterochromaffin-like cell hyperplasia, neuroendocrine tumor, atrophy, metaplasia and adenocarcinoma. In the studies in humans, however, despite enterochromaffin-like cell hyperplasia, the other effects, neuroendocrine tumor and gastric atrophy, gastric metaplasia and or adenocarcinoma, were not identified. Although it is not possible to say that the long-term treatment with proton pump inhibitors induces the appearance or accelerates the development of gastric cancer in humans, several authors have suggested that prolonged administration of this drug could provoke the development of gastric cancer. Thus, the evidence demonstrated in the animal model as well as the large number of patients who do or will do a long-term treatment with proton pump inhibitors, justifies the maintenance of this important line of research.

High degree of duodenal inflammation in Nigerians with functional dyspepsia

BackgroundFunctional dyspepsia (FD) is a heterogeneous disorder associated with diverse pathophysiological mechanisms, including immune activation and low-grade mucosal inflammation. Genetic factors, physiological functions, and environmental factors may determine the relative importance of various pathophysiological mechanisms. This study was designed to determine the histological alterations in the duodenal mucosa of Nigerian patients with FD.MethodsConsecutive patients with dyspepsia seen over a 27-month period in two gastrointestinal endoscopy facilities in Enugu, South-East Nigeria were further evaluated with upper gastrointestinal endoscopy and duodenal mucosal biopsies if no lesion was found in the upper gastrointestinal tract. Patients with heartburn and/or regurgitation who did not have any dyspeptic symptoms and did not have any lesion in the upper gastrointestinal tract on endoscopy were presumed to have non-erosive reflux disease (NERD) and they served as controls. The control subjects also had duodenal biopsies. The histopathological findings in the cases and controls were compared.ResultsThere were 68 patients with FD and 52 patients with NERD. The total inflammatory score was 242 in FD and 66 in NERD (Mann-Whitney U =1168, P=0.0011). Similarly, the scores for chronic inflammation, gastric metaplasia, neutrophilic activity, eosinophilic infiltration, and Helicobacter pylori were significantly higher in FD than NERD.ConclusionFunctional dyspepsia is associated with a high degree of inflammation in the duodenal mucosa. This may reflect the high prevalence of gastrointestinal infections in a tropical environment such as Nigeria. These findings may have therapeutic potential that further studies might elucidate.

Increased Toll-like receptor 5 expression indicates esophageal columnar dysplasia

Toll-like receptor 5 (TLR5) is an immune receptor, which recognizes bacterial flagellin. Increased expression has been reported in various premalignant and malignant lesions indicating a role in carcinogenesis. We assessed the expression of TLR5 in normal esophageal squamous epithelium, Barrett's esophagus with and without dysplasia, and in esophageal adenocarcinoma. Specimens with normal esophagus (n=93), gastric (n=75) or intestinal metaplasia (n=53) without dysplasia, and low-grade (n=56) or high-grade dysplasia (n=33) and esophageal adenocarcinoma (n=94) were studied. TLR5 immunohistochemical stainings were analyzed for the proportion of positive cells and the intensity of expression. In normal squamous epithelium, only the basal third showed TLR5 expression. In esophageal gastric or intestinal metaplasia, expression was present in majority of the cells but significantly weaker (p<0.001) than in dysplastic epithelium. In dysplasia, expression extended to the apical cytoplasm, contrasting basolateral expression in non-dysplastic columnar epithelium. Receiver operating characteristic curve analysis showed that moderate to high expression intensity of TLR5 indicates low-grade dysplasia with 86 % sensitivity and 83 % specificity. Carcinomas showed increased expression in comparison with non-dysplastic columnar epithelium, but there was no association with prognosis. Our results indicate that the esophageal columnar dysplasia is associated with clear increase of TLR5 expression and dissolution of regular polarized expression. TLR5 staining provides a possible biomarker for the recognition of low-grade dysplasia. In addition, the findings suggest a role for abnormal expression of TLR5 in the pathogenesis of esophageal adenocarcinoma and suggest importance of altered microbiome in the pathogenesis of complications of Barrett's esophagus.

Crohn enteritis–associated small bowel adenocarcinomas exhibit gastric differentiation

Primary small bowel adenocarcinoma is rare. Although generally similar to colonic adenocarcinoma, some small bowel adenocarcinomas exhibit unique morphologic features, particularly those arising in association with Crohn disease. In this study, 15 sporadic small bowel adenocarcinomas and 11 Crohn enteritis-associated small bowel adenocarcinomas were examined for histology and immunohistochemical profile including cytokeratins (CK) 7 and 20, intestinal markers CDX2 and MUC2, and gastric epithelial markers MUC5AC and MUC6. We found that Crohn enteritis-associated small bowel adenocarcinomas frequently resemble gastric tubular adenocarcinoma histologically. In addition, when compared to sporadic small bowel adenocarcinoma, the former expressed MUC5AC and MUC6 with much higher frequency (82% vs. 7% and 73% vs. 0%, respectively). Ten of 11 Crohn enteritis-associated small bowel adenocarcinomas (91%) were positive for at least one gastric-type marker (MUC5AC or MUC6). Expression of CK7 was also more frequent in Crohn enteritis-associated small bowel adenocarcinoma (73% versus 27%) while expression of CK20 was less frequent (64% vs. 100%). There was no difference between sporadic and Crohn enteritis-associated small bowel adenocarcinoma in expression of CDX2 (100% vs. 91%) and MUC2 (93% vs. 73%). These observations suggest that there is a difference in the morphologic and immunohistochemical characteristics of sporadic versus Crohn enteritis-associated small bowel adenocarcinoma, particularly in their expression of gastric-type mucin. The findings also suggest that gastric differentiation in Crohn enteritis-associated small bowel adenocarcinoma is related to gastric metaplasia, a common phenomenon in Crohn disease.

Two-Year Subjective, Objective, Quality of Life, and Endoscopic Follow-up After Laparoscopic Nissen-Rossetti in Patients With Columnar-lined Esophagus

Barrett esophagus (BE) is a complication of gastroesophageal reflux disease. We wish to determine the effects of surgery on the histology of the esophageal mucosa and evaluate Quality of Life. Twenty-seven patients with columnar-lined esophagus (CLE) metaplasia underwent laparoscopic Nissen-Rossetti fundoplication. Patients were submitted to close follow-up. One patient voluntarily left follow-up after surgery. CLE was still present in 18 patients (66.6%); no patient developed dysplasia or esophageal adenocarcinoma. Two patients with gastric metaplasia and 1 patient with intestinal metaplasia had regression at 12 and 24 months after surgery (11.1%). DeMeester and Johnson score decreased from 38.69 (SD ± 51.44) to 11.99 (SD ± 18.08) at 6 months, 12.69 (SD ± 12.91) at 12 months, and it was 11.38 (SD ± 6.43) at 24 months. Preoperative gastroesophageal reflux disease-health related quality of life was 19.90 (SD ± 18.54), 9.80 (SD ± 8.77) at 6 months, 9.57 (SD ± 9.14) at 12 months, and 11.53 (SD ± 6.48) at 24 months. Short form-36 measurement showed significant improvement. Management of CLE requires multidisciplinary approach. Medical therapy does not prevent biliary reflux into the esophagus. Surgical therapy is effective and long lasting. It should be performed by experienced surgical teams.

Expression of cyclin D1 and p21(WAF1/CIP1) in human gastric carcinoma and its clinicopathologic significance.

e15114 Background: The deregulation of cyclin, cyclin-dependent kinases (CDKs) and their inhibitors could have a crucial role in the development of diverse human cancers. Alterations in cell cycle regulators and subsequent deregulation of the cell cycle are frequently involved in tumorigenesis and/or tumor progression. The aim of our study was to detect the abnormal expression of cyclin D1 and p21(WAF1/CIP1)in gastric carcinoma and investigate its clinicopathologic significance. Methods: Proteins of cyclin D1 were detected by immunohistochemistry in 80 cases of advanced gastric carcinoma, and 30 cases of benign gastric diseases (chronic gastritis, atrophic gastritis, gastric metaplasia, and gastric dysplasia). From each patient formaldehyde–fixed paraffin sections were stained and examined by immunohistochemistry using monoclonal antibodies.All tumor cells with distinct nuclear staining were considered positive. Results: Sixty-five patients were male and forty five female. Normal gastric epithelium showed consistently positive immunostain for p21WAF1/CIP1. Loss of p21WAF1/CIP1 expression was noted in 65% of intestinal type adenocarcinoma and in 90% of diffuse type adenocarcinoma. Overexpression of cyclin D1 was detected in 90% of advanced gastric carcinomas. Among the various clinicopathological findings, overexpression of cyclin D1 was associated with lymph-node metastasis (P=0.003) and recurrence (P=0.044). Loss of p21WAF1/CIP1 expression was more frequent in diffuse type cancers (P=0.005) and was correlated with recurrence (P=0.002) and death (P=0.001). Conclusions: These findings suggest that overexpression of cyclin D1 is a frequent finding in gastric cancer and immunohistochemical analysis for cell cycle regulators, might be a useful prognostic indicator in gastric cancer.

Esophageal atresia: metaplasia, Barrett

Barrett's esophagus is characterized by the replacement of squamous epithelium by columnar epithelium that is intestinal metaplasia-positive or -negative in the distal esophagus. Gastroesophageal reflux disease, which is frequent and prolonged in esophageal atresia, probably plays a major role in the development of Barrett's esophagus through repeated mucosal damage. Long-term acid exposure contributes to carcinogenesis in Barrett's esophagus of intestinal type, but its effect on gastric metaplasia is less well defined. Recent studies have suggest that metaplasia arises in about 15% of patients with esophageal atresia, with a lag time to developing metaplasia from initial surgical correction of about 10 years. Preliminary data from an ongoing multicenter study including 88 patients with esophageal atresia aged 15-19 years showed gastric metaplasia in 42% of patients (29 fundic and 7 cardial metaplasia), while one patient presented intestinal metaplasia. Esophageal mucosal abnormalities can be observed in esophageal atresia patients at endoscopy despite the absence of symptoms. Whether prolonged, aggressive, acid suppression is beneficial in these situations remains to be determined. Barrett's metaplasia can be removed by endoscopic mucosal resection or destroyed with endoscopic ablative techniques, such as photodynamic therapy, radiofrequency ablation, and cryotherapy. The risk of developing esophageal carcinoma is still a controversial issue as only a few clinical cases have been reported in young adults with esophageal atresia. As late complications of esophageal atresia, particularly esophagitis and Barrett's esophagus, are increasingly being recognized, long-time systematic follow up of the esophageal mucosa including multistage biopsies is therefore required even in asymptomatic patients.

Confocal Laser Endomicroscopy in Diagnostics of Complications of Gastroesophageal Reflux Disease in Children

Twenty-nine children with suspected gastroesophageal reflux disease (GERD) and 17 children as a reference group were enrolled in the study. A conventional white light endoscopy of the oesophagus was supplemented by a probe-based confocal laser endomicroscopy (pCLE) and followed by a biopsy for histological examination. A comparative analysis of endoscopic, endomicroscopic, and histological data were performed. The pCLE allows detecting oesophagitis with the sensitivity and specificity of 93% and 94%, respectively; gastric and intestinal metaplasia typical for Barrett oesophagus with 83% and 100%, respectively; and polyps of the cardioesophageal passage with the sensitivity of 89% in patients with long-term GERD. Thus, this method allows taking an optical biopsy of pathological changes of esophageal mucosa just during the standard endoscopic investigation. DOI: http://dx.doi.org/10.11593/bje.2013.0102.0012 Bangladesh Journal of Endosurgery Vol.1(2) May 2013: 1-6

Su1521 Esophageal “Outlet Patches”: Endoscopic, Histologic and Electronmicroscopic Description of New Lesions (Small Vesicles Containing Gastric Metaplasia and Submucosal Glands) At the Gastroesoophageal Jucntion

Su1521 Esophageal “Outlet Patches”: Endoscopic, Histologic and Electronmicroscopic Description of New Lesions (Small Vesicles Containing Gastric Metaplasia and Submucosal Glands) At the Gastroesoophageal Jucntion