Areas Of Intestinal Metaplasia Research Articles

Helicobacter pylori Eradication Reverses DNA Damage Response Pathway but Not Senescence in Human Gastric Epithelium.

Helicobacter pylori (H. pylori) infection induces DNA Double-Strand Breaks (DSBs) and consequently activates the DNA Damage Response pathway (DDR) and senescence in gastric epithelium. We studied DDR activation and senescence before and after the eradication of the pathogen. Gastric antral and corpus biopsies of 61 patients with H. pylori infection, prior to and after eradication treatment, were analyzed by means of immunohistochemistry/immunofluorescence for DDR marker (γH2AΧ, phosporylated ataxia telangiectasia-mutated (pATM), p53-binding protein (53BP1) and p53) expression. Samples were also evaluated for Ki67 (proliferation index), cleaved caspase-3 (apoptotic index) and GL13 staining (cellular senescence). Ten H. pylori (-) dyspeptic patients served as controls. All patients were re-endoscoped in 72-1361 days (mean value 434 days), and tissue samples were processed in the same manner. The eradication of the microorganism, in human gastric mucosa, downregulates γH2AΧ expression in both the antrum and corpus (p = 0.00019 and p = 0.00081 respectively). The expression of pATM, p53 and 53BP1 is also reduced after eradication. Proliferation and apoptotic indices were reduced, albeit not significantly, after pathogen clearance. Moreover, cellular senescence is increased in H. pylori-infected mucosa and remains unaffected after eradication. Interestingly, senescence was statistically increased in areas of intestinal metaplasia (IM) compared with adjacent non-metaplastic mucosa (p < 0.001). In conclusion, H. pylori infection triggers DSBs, DDR and senescence in the gastric epithelium. Pathogen eradication reverses the DDR activation but not senescence. Increased senescent cells may favor IM persistence, thus potentially contributing to gastric carcinogenesis.

Intravesical urachal cyst masquerading as a bladder malignancy: a case report

BackgroundUrinary bladder masses in children are extremely rare. Certain benign conditions (e.g., ureterocele) can mimic malignant bladder masses. In this report, we present a unique case of a urachal cyst masquerading as a bladder malignancy. Unlike the typical location of urachal cysts along the course of the urachal tract, the cyst in this case was unexpectedly situated within the urinary bladder, leading to diagnostic difficulties.Case presentationA 2-year-old Bahraini boy presented with hematuria and dysuria for 2 weeks. There was no history of fever, abdominal pain, or vomiting. Physical examination yielded normal findings. Urinalysis showed numerous red blood cells and revealed positive results for nitrites and leukocyte esterase. Abdominal ultrasound showed a well-defined soft tissue lesion with internal vascularity located at the apex of the urinary bladder. Subsequently, magnetic resonance imaging demonstrated a thick-walled cystic structure arising from the anterosuperior wall of the bladder and protruding into its lumen. The patient underwent complete excision of the bladder lesion for the presumed diagnosis of rhabdomyosarcoma. Histopathological examination showed a fluid-filled space lined by stratified squamous epithelium with areas of intestinal metaplasia, revealing an unexpected diagnosis of a urachal cyst. The patient was discharged with complete resolution of symptoms.ConclusionsIntravesical urachal cysts are a rare type of congenital urachal anomaly that may simulate a bladder malignancy, particularly if associated with infection. This case emphasizes the importance of considering urachal cysts in the differential diagnosis of bladder masses, especially in children, and specifically when the lesion is midline in the anterosuperior wall of the bladder.

Histopathological Evaluation of Gastric Mucosal Atrophy for Predicting Gastric Cancer Risk: Problems and Solutions.

Patients suffering from chronic gastritis and developing gastric mucosa atrophy are at increased risk of the development of gastric cancer. The diagnosis of chronic atrophic gastritis (CAG) is a complex procedure involving a detailed history taking, a thorough physical examination and the use of laboratory and instrumental diagnostic methods among which the endoscopy of the upper digestive tract is the cornerstone because it allows the assessment of the topography of gastritis and identification of erosions and areas of intestinal metaplasia with the use of NBI endoscopy. However, the diagnosis of CAG requires morphological examination of the gastric mucosa. So, in addition to assessing macroscopic changes in the gastric mucosa, it is necessary to take biopsy specimens in accordance with the protocols for their morphological and immunohistochemical examination. In the absence of specific diagnostic stigmas of CAG, close cooperation between a clinician, endoscopist and pathologist is necessary. The article presents systematized data on the histopathological assessment of the gastric mucosa atrophy to predict the risk of gastric cancer.

Патогенетическая роль изменений системы оксида азота при инфицировании различными генотипами Helicobacter pylori

Introduction. Helicobacter pylori (Hp) is a class I biological carcinogen and the third leading cause of cancer death in the world, according to the World Health Organization. Hp infection represents a global public health problem in the 4.4 billion people living with Hp worldwide. The pathogenesis of helicobacteriosis is multifaceted: disorders in the nitric oxide (NO) system are involved in the development of the disease, along with other mechanisms. These aspects of the pathogenesis of helicobacteriosis are not well understood. In particular, such parts of the general problem as the significance of changes in the level of NO, its metabolites in the development of inflammatory and erosive-ulcer diseases of the gastroduodenal zone caused by different genotypes of Hp are not solved. After HP eradication, the content of NO synthase in the gastric mucosa decreases. However, the expression of the enzyme remains high in areas of intestinal metaplasia, which is considered the source of continued production of NO synthase even after Hp eradication. Aim. To investigate the level of nitrates/nitrites in the blood in patients infected with various genotypes of Hp. Materials and methods. 48 patients with inflammatory and erosive-ulcer diseases of the stomach and CPD infected with Hp were examined. R&amp;D Systems kits were used to determine the level of nitrates/nitrites in the blood. For the diagnosis of helicobacteriosis, a classic respiratory test was used, as well as a polymerase chain reaction. CagA, VacA, BabA, IceA genotyping Hp was performed. Depending on gene detection, Hp strains were divided into 4 serotypes: type I (CagA+, VacA+)/Type Ia (CagA+, VacA-), type Ib (CagA-, VacA+), type II (Vac A-, CagA-). Discussion. Нр harboured the CagA gene in 34 patients (70.8% of cases), VacA gene in 40 patients (83.3%), BabA gene in 6 patients (12.5%), and IceA gene in 8 patients (16.7%). The distribution by Нр serotype showed that serotype I was found in 28 patients (58.3%), serotype Ia in 6 patients (12.5%), serotype Ib in 12 patients (25.0%), and serotype II in 2 patients (4.2%). In general, all surveyed patients had blood levels of nitrates/nitrites that were significantly increased to 54.7±2.4 μmol/L (compared to the levels of healthy individuals, p&lt;0.05). The patients infected with the CagA-positive Нр strains had the highest blood levels of NO metabolites. Conclusions. In helicobacteriosis, the level of NO metabolites in the blood is increased, especially in patients infected with CagA+, IceA+ strains of Hp. This is the basis for the development of a differentiated treatment for inflammatory and erosive-ulcer diseases of the gastroduodenal zone associated with different strains of Hp.

S3615 Gastric Neuroendocrine Tumor of Indeterminate Type

Introduction: Gastric neuroendocrine tumors (GNETs) are rare tumors making up less than 2% of gastric polyps. Type I GNETs are most common (70-80%) and are associated with atrophic gastritis, pernicious anemia, iron deficiency, elevated gastrin, and high gastric pH. These are typically small, low-grade, and may be multifocal. Type II tumors are also associated with elevated gastrin levels but a low pH, as seen in Zollinger-Ellison syndrome. Type III tumors are larger and more aggressive and occur sporadically in the setting of normal gastric mucosa, normal gastrin levels, and normal pH. Here we discuss an unusual case of GNET which does not fit into either category. Case Description/Methods: A 70-year-old white male with history of gastroesophageal reflux disease (GERD) on chronic proton pump inhibitor (PPI) presented for esophagogastroduodenoscopy (EGD) for worsening GERD symptoms. EGD revealed 2 polyps in the body – each was 4-5 mm and was removed with hot snare. A few smaller polyps were removed with biopsy forceps. The gastric mucosa was grossly normal. Sydney protocol biopsies were obtained. The 2 larger polyps returned as well-differentiated GNETs, grade 1 (Ki-67 index 2.5%). The smaller polyps returned as areas of intestinal metaplasia (IM), but Sydney protocol biopsies did not reveal H. pylori, atrophic gastritis, or IM. EGD was repeated off PPI for 1 week and fasting labs were obtained. Gastric pH was 1, serum gastrin was 78 pg/mL (normal), vitamin B12 and ferritin were normal, and intrinsic factor and parietal cell antibodies were negative. (Figure) Discussion: This case highlights a scenario in which a GNET is difficult to categorize based on classic criteria. As type III lesions are very aggressive with high risk of metastasis, distinguishing between type I and type III lesions is paramount. While grossly and histologically resembling a type I GNET (multifocal, small, low-grade), the GNETs in this case were present in the absence of atrophic gastritis, and the patient had a normal gastrin and low gastric pH off PPI. The lack of atrophic gastritis and normal gastrin levels are more suggestive of a type III tumor, but one would expect a single, large, high-grade GNET in that case. As PPI use has increased in the past 30 years, so has incidence of GNETs; it is possible that a chronic, PPI-induced “hyper-gastrin” state was responsible for this patient’s GNETs and that gastrin normalized once PPI was discontinued. More studies are needed to further categorize GNETs with indeterminate features.Figure 1.: Gastric Polyp.

Effects of Granule Dendrobii on chronic atrophic gastritis induced by N-methyl-N'-nitro-N-nitrosoguanidine in rats.

BACKGROUND Dendrobium officinale is an herb of Traditional Chinese Medicine (TCM) commonly used for treating stomach diseases. One formula of Granule Dendrobii (GD) consists of Dendrobium officinale and American Ginseng (Radix Panacis quinquefolii), and is a potent TCM product in China. Whether treatment with GD can promote gastric acid secretion and alleviate gastric gland atrophy in chronic atrophic gastritis (CAG) requires verification.AIMTo determine the effect of GD treatment on CAG and its potential cellular mechanism.METHODSA CAG model was induced by feeding rats N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) for 12 wk. After oral administration of low, moderate, and high doses of GD in CAG rats for 8 wk, its effects on body weight, gastric mucosa histology, mucosal atrophy, intestinal metaplasia, immunohistochemical staining of proliferating cell nuclear antigen (PCNA) and B-cell lymphoma-2, and hemoglobin and red blood cells were examined.RESULTSThe body weights of MNNG-induced CAG model rats before treatment (143.5 ± 14.26 g) were significantly lower than that of healthy rats (220.2 ± 31.20 g, P < 0.01). At the 8th week of treatment, the body weights of rats in the low-, moderate-, and high-dose groups of GD (220.1 ± 36.62 g) were significantly higher than those in the untreated group (173.3 ± 28.09 g, all P < 0.01). The level of inflammation in gastric tissue of the high-dose group (1.68 ± 0.54) was significantly reduced (P < 0.01) compared with that of the untreated group (3.00 ± 0.00, P < 0.05). The number and thickness of gastric glands in the high-dose group (31.50 ± 6.07/mm, 306.4 ± 49.32 µm) were significantly higher than those in the untreated group (26.86 ± 6.41/mm, 244.3 ± 51.82 µm, respectively, P < 0.01 and P < 0.05), indicating improved atrophy of gastric mucosa. The areas of intestinal metaplasia were significantly lower in the high-dose group (1.74% ± 1.13%), medium-dose group (1.81% ± 0.66%) and low-dose group (2.36% ± 1.08%) than in the untreated group (3.91% ± 0.96%, all P < 0.01). The expression of PCNA in high-dose group was significantly reduced compared with that in untreated group (P < 0.01). Hemoglobin level in the high-dose group (145.3 ± 5.90 g/L), medium-dose group (139.3 ± 5.71 g/L) and low-dose group (137.5 ± 7.56 g/L) was markedly increased compared with the untreated group (132.1 ± 7.76 g/L; P < 0.01 or P < 0.05).CONCLUSIONTreatment with GD for 8 wk demonstrate that GD is effective in the treatment of CAG in the MNNG model by improving the histopathology of gastric mucosa, reversing gastric atrophy and intestinal metaplasia, and alleviating gastric inflammation.

Diagnostic Accuracy of EndoFaster® and Narrow-Band Imaging Endoscopy in Patients with Impaired Gastric Acid Secretion: A Real-Time Prospective Study.

Background EndoFaster® analyzes gastric juice in real time during gastroscopy allowing the detection of hypo-achlorhydric conditions, like corpus atrophic gastritis. Narrow-band imaging (NBI) endoscopy allows to accurately detect and perform target biopsies in areas of intestinal metaplasia, a histological change often associated to corpus atrophic gastritis. Aims To compare the diagnostic accuracy of EndoFaster® with histological evaluation for corpus atrophic gastritis through high-resolution (HR) NBI targeted biopsies. Methods Prospective study on consecutive adult patients undergoing gastroscopy between April and November 2018. Patients in therapy with proton pump inhibitors, previous gastric surgery, and/or known gastric neoplasia were excluded. At the beginning of gastroscopy, gastric juice was aspirated and analyzed by EndoFaster® in 15 seconds. Endoscopists were blinded to the report of EndoFaster®. Evaluation of gastric mucosa in HR-white light was firstly performed, then with HR-NBI allowing to perform targeted biopsies on areas suspected for intestinal metaplasia; otherwise, biopsies were performed according to the updated Sydney System protocol and sent for histopathological evaluation. Results Overall, 124 patients were included [64% F; 56 (18-85) years]. Corpus atrophic gastritis was present in 41.9% of patients. EndoFaster® showed an accuracy for corpus atrophic gastritis diagnosis, compared to histopathological evaluation as gold standard, of 87.1% and a sensitivity, specificity, PPV, and NPV of 78.8%, 93.1%, 89.1%, and 85.9%, respectively. pH showed a positive correlation with the severity score of atrophy (r = 0.67, 95% CI: 0.73-0.81, and p < 0.0001). EndoFaster® allowed to diagnose corpus atrophic gastritis in 3.7% of patients negative to NBI (corpus atrophic gastritis without intestinal metaplasia). Conclusion EndoFaster® seems a promising tool to diagnose corpus atrophic gastritis. The evaluation of hypo-achlorhydria during gastroscopy can address bioptic sampling in corpus atrophic gastritis patients without intestinal metaplasia.

DINAMIC SCREENING OF PRECANCEROUS ESOPHAGUS USING MOLECULAR GENETIC ANALYSIS

Introduction. Esophageal adenocarcinoma develops from areas of intestinal metaplasia in Barrett’s esophagus, similar to how intestinal metaplasia transforms into gastric adenocarcinomas in the stomach. Atypia with intraepithelial neoplasia is difficult to distinguish from reactive and regenerative changes, especially in erosive mucosa of the esophagus. Observation of patients with Barrett’s esophagus allows the identification of adenocarcinoma in the earlier, more curable stages in many patients.The aim of our study was to study the prospects of using a classifier based on miRNA profiling in histological samples of Barrett’s esophagus to determine the risk of malignancy and treatment tactics.Material and Methods. In this study, 119 samples of archival histological material in the form of paraffin blocks were used: 89 samples of gastric mucosa with dysplasia and 30 samples of Barrett’s esophagus. The expression level of miRNA-145-5p, -150-5p, -20a-5p, -21-5p,-31-5p,-34a-5p,-375 was determined using real-time RT-PC R. Samples were stratified into different groups using the C-RT decision tree algorithm.Results. 26.7 % of Barrett’s esophagus samples were classified by expression of the proposed miRNAs as cancer, which may indicate a potential development of a malignant tumor in the mucosa of the esophagus when morphological changes have not yet been found.

S1903 A Case of Barrett’s Esophagus With Low-Grade Dysplasia Progressing to Esophageal Adenocarcinoma Despite Radiofrequency Ablation and Vigilant Surveillance

INTRODUCTION: Surveillance of Barrett’s Esophagus (BE) depends on degree of dysplasia, which is separated into low-grade dysplasia (LGD) or high-grade dysplasia (HGD). For patients with confirmed LGD, radiofrequency ablation (RFA), is the procedure of choice, with over 90% successful eradication at two year follow up. Reports of progression of LGD to esophageal adenocarcinoma (EAC) after RFA treatment is as low as 0.25%. CASE DESCRIPTION/METHODS: A 63-year-old man with a longstanding history of heartburn underwent an EGD that demonstrated long-segment BE, classified as C8-M10 (Image 1). Biopsies demonstrated non-dysplastic BE. Approximately 1.5 years later, EGD #2 demonstrated the same degree of mucosal findings; however, biopsies now revealed LGD (Figure 1, Timeline of EGDs). 8 months later, the patient was treated with RFA at the entire area of intestinal metaplasia. 2 months later, EGD #4 demonstrated BE now measuring C4-M9, again requiring RFA. The patient returned 6 months later, and EGD #5 demonstrated only 1 significant island of columnar mucosa, with biopsies showing no evidence of BE. 6 months later, repeat EGD #6 demonstrated near complete eradication of BE with only 3 sub-centimeter islands of columnar mucosa. Biopsies of these areas demonstrated intestinal metaplasia without dysplasia. EGD #7 performed 8 months later revealed 2 tiny islands of columnar mucosa with no dysplasia. EGD #8 was performed 1.5 years later with no evidence of BE and biopsies revealed complete eradication of intestinal metaplasia (CEIM). Patient was instructed to follow up for repeat EGD in 6 months, but he returned 1.5 years later and EGD #9 demonstrated a small island of BE with foci indefinite for dysplasia. A year later, EGD #10 demonstrated a new 2 cm nodule (Image 2). Biopsy revealed invasive well-differentiated adenocarcinoma, requiring neoadjuvant chemotherapy with proximal esophageal resection. DISCUSSION: We present a case in which BE with LGD was treated with RFA with CEIM and aggressive endoscopic follow up, but nonetheless had an unlikely progression to EAC requiring esophagectomy. A meta-analysis demonstrated recurrence of dysplasia carried a 0.9% risk and development to EAC carried a risk of 0.7% at 1.5 years. For patients with baseline LGD, it has been proposed that surveillance intervals be lengthened to 1, 3, and 5 years after CEIM. However, our case suggests surveillance guidelines should continue to be aggressive for LGD post RFA, especially in the case of long-segment BE.Figure 1.: Initial EGD demonstrating long-segment BE, classified as C8-M10.Figure 2.: Appearance of 2cm nodule in the distal esophagus seen on EGD #10.Figure 3.: Timeline of events for BE course.

Telepathology a Useful Method in the Diagnosis Digestive Biopsies with Rare Entities. Case Presentation of a Collagenous Gastritis.

Introduction/ Background Collagenous gastritis is a rare entity in current surgical pathology practice. Since the introduction of the term until present, only small series and isolated cases have been reported, generally by high-specialized centers in gastrointestinal pathology. In current practice, the diagnosis of this unusual affection is based on clinical data corroborated with endoscopic and pathological findings. Due to the small number of cases the diagnostic criteria are partly taken from microscopic colitis diagnosis. Thus, it is considered that the association of the appropriate clinical context (stomach pain, watery diarrhea, endoscopic nodular appearance) and histological gastritis changes with collagen deposition of dense material with a 10um minimum variable thickness that comprises capillaries and inflammatory elements. The technical advantage of a digital slide scanner is allowing access to an experienced pathologist in digestive pathology’s opinion and conducting precision measurement. Aims Our presentation brings to attention of pathologist community a rarely diagnosed entity and the advantages of tele-pathology in timely accessing an expert opinion and performing accurate measurements. Methods We received gastric biopsy samples endoscopically taken from a 56-year female who complained of transit disorders, vomiting, epigastric pain that did not improve after IPP treatment. On endoscopy exam a nonspecific aspect with discrete erythema and vaguely nodular appearance of the gastric mucosae was noted. The specimens were paraffin embedded, and serial sections were stained HE, AB-PAS and MGG. The obtained slides were fully scanned and a gastrointestinal pathology expert advice was requested. Subsequently, a Mason’s Trichrome stain and tenascin immunohistochemistry test were performed. The examined section showed gastric mucosal epithelium with scarce intraepithelial lymphocytes (5-6 lymphocytes/100 cells). The surface epithelium had the tendency to roll away from the variable thickened stroma. The glandular architecture and chorion were modified by a nonspecific inflammatory infiltrate. A diagnose of chronic inactive gastritis with intestinal metaplasia areas was propose, and an expert opinion was requested. Digitally scanned sections using the Leica II Aperio slide scanner were taken. Examination of slides was made using the Imagescope12.2 Leica. Micrometeric measurements of the hyaline material varied between 9.5-51um. The review of glass slides on traditional optical microscope was made confirming the diagnosis. Results Collagenous gastritis remains an underestimated condition due to its low incidence and lack of expertise in the field. Hence telepathology becomes a useful tool for requesting a second opinion and precisions measurements.

Biliary dysplasia in primary sclerosing cholangitis harbors cytogenetic abnormalities similar to cholangiocarcinoma.

Grading criteria for biliary dysplasia associated with primary sclerosing cholangitis (PSC) have been recently described. Although a dysplasia to cholangiocarcinoma (CCA) sequence is implied, supportive data are lacking. Seventeen liver explants with biliary dysplasia from patients with PSC were selected. Formalin-fixed, paraffin-embedded blocks from each patient were evaluated to identify areas of normal/reactive biliary epithelium, intestinal metaplasia, low-grade dysplasia, high-grade dysplasia, and CCA. Areas of interest were assessed for chromosomal alteration with fluorescence in situ hybridization using probes directed to locus 9p21 and centromeres 3, 7, and 17. The cutoffs for calling probe copy number abnormalities for polysomy, single locus gain, and homozygous 9p21 loss were established by receiver operating characteristic curve analysis. Of 4 areas of intestinal metaplasia, 19 low-grade dysplasias, 19 high-grade dysplasias, and 5 CCAs, 0%, 11%, 58%, and 40% displayed polysomy and 0%, 0%, 16%, and 40% exhibited homozygous 9p21 loss as the most severe abnormality, respectively. Patients with prior or current CCA were more likely to display polysomy in dysplasia than patients without CCA (70% versus 14%; P = .05); however, high-grade dysplasia was proportionally more common in the CCA-associated dysplasia group. Polysomy and homozygous 9p21 loss are detected in biliary dysplasia and CCA. These findings support a dysplasia-carcinoma sequence in PSC patients and suggest that fluorescence in situ hybridization analysis could help refine the grading of biliary dysplasia in these patients.

Mucin profile of Upper Gastrointestinal Tract Lesions

Background: Mucin secretions reflect the composition changes in the functional state of the mucosa in health and disease of the upper gastrointestinal tract. Objectives: To study the different types of upper gastrointestinal tract lesions and to determine the role of mucin histochemistry in the interpretation of lesions of upper gastrointestinal tract. Methods: A prospective study from September 2006 to August 2007 was carried out. 60 endoscopic biopsy specimens obtained from upper gastrointestinal tract lesions from the department of Gastroenterology at R.L. Jalappa Hospital & Research Centre was sent for histopathological examination. All the sections were stained by routine Haematoxylin and Eosin stain followed by special stains for mucins i.e Alcian blue pH 2.5 / PAS and Hale\'s Colloidal Iron. Results: Age of presentation of various upper gastrointestinal lesions was between 26-90 years. Females dominated the study group i.e. 39 (65%) when compared to males i.e. 21 (35%). Alcian Blue/Periodic Acid Schiff (AB/PAS) staining in oesophageal lesions could detect mixture of acidic mucins & neutral mucins and sulphomucins in Barrett\'s oesophagus. In gastritis, predominantly mixture of acidic and neutral mucins and in one case, sulphomucins were detected. Adenocarcinoma of stomach showed combination of acidic and neutral mucins. Duodenitis showed acidic, neutral and sialomucins. Adenocarcinoma of duodenum showed combination of acidic & neutral mucins. Hale\'s Colloidal Iron (HCI) stain in inflammatory & neoplastic lesions of stomach & duodenum, could detect only acidic mucins. Conclusion: In neoplastic condition of stomach this study suggests that those tumours which secrete neutral and mixed mucins probably arise from gastric epithelium and neck cells of the gastric glands. In those cases where the tumour produces acidic mucins it is possible the tumour arose from areas of intestinal metaplasia. Key words: Mucins, Histochemistry, Alcian Blue / Periodic Acid Schiff, Hale\'s Colloidal Iron

Aberrant expression of intelectin-1 in gastric cancer: its relationship with clinicopathological features and prognosis

Human intelectin-1 (ITLN-1) is a novel identified galactose-binding lectin that is expressed in the colonic goblet cells. Since gastric adenocarcinomas can arise through a process of intestinalization, we speculate that ITLN-1 may be aberrantly expressed in gastric cancer. This study was undertaken to examine the ITLN-1 expression in gastric cancer and correlate it with clinical outcomes. One hundred and ninety-six gastric cancer patients were evaluated for the ITLN-1 expression by immunohistochemistry. The ITLN-1 transcripts were measured by real-time quantitative PCR. ITLN-1 expression was absent in normal gastric mucosa, whereas areas of intestinal metaplasia revealed ITLN-1 immunoreactivity. One hundred and forty-two gastric cancer patients (72.4%) were positive for ITLN-1 expression. In a subtotal of 20 patients, ITLN-1 transcripts were significantly enhanced in gastric cancer tissues than in normal gastric mucosa (P<0.001). The expression rate of ITLN-1 was higher in intestinal-type carcinomas than in diffuse-type carcinomas (P=0.003). ITLN-1 positivity in gastric cancer was positively correlated with tumor differentiation (P=0.001) and CDX2 expression (P<0.001), and inversely correlated with depth of invasion (P=0.007), lymph node metastasis (P=0.001), distant metastasis (P=0.014), clinical stage (P=0.006), Ki-67 expression (P=0.001), and heparanase expression (P<0.001), without correlation with age, gender, tumor location, or tumor size. In univariate and multivariate analyses, ITLN-1 was an independent prognostic factor for longer survival of gastric cancer patients (P=0.001). The aberrant ITLN-1 expression in gastric cancer is correlated with clinicopathological features and may be a useful prognostic factor for predicting the outcomes of gastric cancer patients.

Fluorescence in situ hybridization mapping of esophagectomy specimens from patients with Barrett's esophagus with high-grade dysplasia or adenocarcinoma

The progression of intestinal metaplasia to esophageal adenocarcinoma in patients with Barrett's esophagus is partly driven by chromosomal alterations that activate oncogenes and inactivate tumor suppressor genes. The goal of this study was to determine how alterations of 4 frequently affected genes correlate with the range of histopathologic lesions observed in resected esophagi of patients with Barrett's esophagus. Fluorescence in situ hybridization was used to assess 83 tissue sections from 10 Barrett's esophagus esophagogastrectomy specimens for chromosomal alterations of 8q24 (MYC), 9p21 (CDKN2A; alias P16), 17q12 (ERBB2), and 20q13.2 (ZNF217). Histologic lesions assessed included gastric metaplasia (n = 8), intestinal metaplasia (n = 43), low-grade dysplasia (n = 28), high-grade dysplasia (n = 25), and adenocarcinoma (n = 16). Histologic maps showing the correlation between fluorescence in situ hybridization abnormalities and corresponding histology were created for all patients. Chromosomal abnormalities included 9p21 loss, single locus gain, and polysomy. A greater number of chromosomal alterations were detected as the severity of histologic diagnosis increased from intestinal metaplasia to adenocarcinoma. All patients had alterations involving the CDKN2A gene. CDKN2A loss was the only abnormality detected in 20 (47%) of 43 areas of intestinal metaplasia. Polysomy, the most common abnormality in dysplastic epithelium and adenocarcinoma, was observed in 16 (57%) of 28 low-grade dysplasia, 22 (88%) of 25 high-grade dysplasia, and 16 (100%) of 16 adenocarcinoma. The findings of this study improve our understanding of the role that chromosomal instability and alterations of tumor suppressor genes such as CDKN2A and oncogenes such as ERBB2 play in the progression of intestinal metaplasia to adenocarcinoma in patients with Barrett's esophagus.

Global DNA hypomethylation is an early event in Helicobacter pylori-related gastric carcinogenesis

AimCancer, particularly gastric cancer (GC), is prevalently an epigenetic phenomenon that is dependent on an altered DNA methylation pattern. In gastric carcinogenesis, many genes show aberrant methylation; however, none of...

Topographic differences in gastric micromucosal patterns observed by magnifying endoscopy with narrow band imaging

The distributions and grades of Helicobacter pylori induced gastritis are known to vary among H. pylori-associated diseases. The aim of this study was to investigate the differences in distributions of gastric micromucosal structures observed by magnifying narrow band imaging (NBI) endoscopy among patients with different H. pylori-associated diseases. Ninety-five patients with active duodenal ulcers (n = 24) and diffuse-type (n = 24) and intestinal-type (n = 47) early gastric cancers were enrolled. The magnified NBI findings were evaluated at the lesser and greater curvatures in the upper gastric corpus and were classified according to the modified A-B classification system. Biopsy specimens were also evaluated. In a total of 190 areas observed with magnifying NBI, histological grading (inflammation, activity, atrophy and intestinal metaplasia) showed significant differences among the classified micromucosal patterns (P < 0.001). Types B-1 and B-2, with mild atrophic changes and few areas of intestinal metaplasia, were seen mostly in the duodenal ulcers group. Types B-3 and A-1, with moderate atrophic changes, were seen in the diffuse-type early gastric cancers at the lesser curvature. Types A-1 and A-2, with severe atrophic change and a high frequency of intestinal metaplasia, were seen in the intestinal-type early gastric cancers at the lesser curvature. The prevalence of micromucosal structures differed significantly among the three groups both at the lesser and greater curvatures (P < 0.001). Magnifying NBI endoscopy clearly revealed detailed micromorphological differences corresponding to the histology and endoscopic findings among patients with different H. pylori-associated diseases.

Localization of Cytochrome P4502E1 Enzyme in Normal and Cancerous Gastric Mucosa and Association with Its Genetic Polymorphism in Unoperated and Remnant Stomach

Exposure to nitroso compounds and the activity of cytochrome P450 2E1 (CYP2E1), an activation enzyme for these carcinogens, are important factors in gastric carcinogenesis. Here, we investigated the potential correlation between genetic variation in CYP2E1 and its enzyme expression as detected with immunohistochemical (IHC) staining and cancer susceptibility in unoperated and remnant stomach. Expression of CYP2E1 in the stomach (n=117) was detected with IHC staining using a polyclonal anti-CYP2E1 antibody. Interindividual variation in CYP2E1 enzyme activity was then compared with genetic polymorphisms in the transcriptional flanking region of the CYP2E1 gene by restriction fragment length polymorphism (RFLP) detection using the Rsa I restriction enzyme. Genetic polymorphisms of Rsa I RFLP in CYP2E1 were investigated in 499 patients with gastric cancer (466 unoperated stomachs and 33 remnant stomachs) and 553 control patients with benign gastroduodenal diseases. Mucosal IHC staining for CYP2E1 was stronger in areas of intestinal metaplasia, particularly in endocrine cells, which stained consistently and strongly. Expression of CYP2E1 enzyme in areas of IHC staining were confirmed with Western blot analysis and showed a significant association between the degree of staining and the CYP2E1 genotype (p<0.01) in cancer tissues and in the foveolar epithelium of normal gastric mucosa. No association between specific CYP2E1 genotype and gastric cancer risk in the unoperated stomach was found in either the large study or the age- and gender-matched case-control study. However, the frequency of rare alleles (C1/C2 or C2/C2) was significantly higher in patients with cancer in the remnant stomach following gastrectomy than in controls subjects without cancer (odds ratio=2.8, 95% confidence interval=1.3-5.8) or those with primary gastric cancer (odds ratio=2.6, 95% confidence interval=1.3-5.5). CYP2E1 genetic polymorphisms might correlate with CYP2E1 enzyme expression levels in normal and cancerous gastric tissues. These polymorphisms do not influence the development of primary stomach cancer but may do so in specific conditions, such as the remnant stomach after gastrectomy.

Diagnosis of Helicobacter pylori Infection

AbstractIf we had to give a general view of the articles published in the year 2010, we should conclude that the evidence in the year 2010 suggests that, also in Helicobacter pylori diagnosis, “the devil is in the details”. In this sense, different studies suggested that skipping citric acid pretreatment or local validation or reducing the 13C‐urea dose markedly decreases the accuracy of the urea breath test. The studies also implied that, even between monoclonal stool tests, there are large differences between the marketed tests. Finally, even histology does not work adequately in patients with gastric cancer or extensive areas of intestinal metaplasia. In these cases, specific gastric sites should be biopsied to improve the reliability of histology.

Expression of resistin-like molecule beta in gastric cancer: its relationship with clinicopathological parameters and prognosis

Resistin-like molecule beta (RELMbeta), an intestinal goblet cell-specific protein, is a biomarker of intestinal metaplasia in Barrett's esophagus and over-expressed in colon cancer. Since gastric adenocarcinomas can arise through a process of intestinalization, we hypothesized that RELMbeta might be aberrantly expressed in gastric cancer. This study was undertaken to examine the RELMbeta expression in gastric cancer and correlate it with clinical outcome. One hundred and thirty-six gastric cancer patients were evaluated for the RELMbeta expression by immunohistochemistry. The RELMbeta transcripts were measured by real-time quantitative PCR. In normal gastric mucosa, RELMbeta expression was absent, whereas areas of intestinal metaplasia revealed RELMbeta reactivity. Eighty-nine patients of gastric cancer (65.4%) were positive for RELMbeta expression. In a subtotal of 20 patients, RELMbeta transcripts were positively correlated with protein levels in gastric cancer tissues, but absent in normal gastric mucosa. The expression rate of RELMbeta was higher in intestinal-type carcinomas than in diffuse-type carcinomas (P < 0.001). RELMbeta positivity in gastric cancer was positively correlated with tumor differentiation (P = 0.001) and inversely correlated with tumor infiltration (P = 0.007), lymph node metastasis (P = 0.035), and heparanase expression (P < 0.001), without correlation with age, gender, tumor location and size, tumor-node metastasis stages, and Ki-67 expression. Patients showing positive RELMbeta expression had a significantly longer overall survival than those with negative expression (P = 0.001). These results provide evidences that the RELMbeta expression in gastric cancer is correlated with clinicopathological features and may be a useful prognostic factor for predicting the outcome of gastric cancer patients.

The expression of adiponectin receptors Adipo-R1 and Adipo-R2 is associated with an intestinal histotype and longer survival in gastric carcinoma

Background:Adiponectin (ApN) is a 30 kDa adipocytokine which mediates an antineoplastic effect after binding to its receptors, Adipo-R1 and Adipo-R2. The expression of these receptors has been documented in gastric...