Gastric Mucosal Biopsy Research Articles

The Optimal Number of Biopsy Fragments to Establish a Morphologic Diagnosis of Eosinophilic Esophagitis

Eosinophilic esophagitis (EoE) is characterized clinically by dysphagia, chest pain, and food impaction, and morphologically by increased numbers of intraepithelial eosinophils and marked basal hyperplasia of the squamous mucosa. The consensus criteria for a diagnosis of EoE include the presence of ≥15 eosinophils/HPF in biopsies from both proximal and distal esophagus in the absence of other causes of esophageal eosinophilia, and the lack of clinical response to proton pump inhibitor therapy. Because of the variability in the distribution of intraepithelial eosinophils among biopsy fragments and the lack of standardized biopsy practices, we sought to determine the optimal number of esophageal biopsies from the mid and distal esophagus needed to reach the minimum morphologic criteria of ≥15 eosinophils/HPF. From 5 January 2009 to 26 September 2011, 771 patients were diagnosed with EoE at our institution. From that patient population, 102 sequential cases were chosen for further study, all of whom had biopsies taken from the mid and distal esophagus. Cases with only gastric mucosa present and biopsies taken from patients with a previous diagnosis of EoE were excluded. The original H&E-stained slides were reviewed, and the number of biopsy fragments containing squamous mucosa was recorded. By using a × 40 objective and × 10 oculars (field diameter=0.52 mm, field area=0.21 mm(2)), the number of eosinophils per high power field (EOS/HPF) in up to three HPFs was counted in each biopsy fragment. The EOS/HPF were counted in 1,342 biopsy fragments. The number of biopsy fragments obtained from the mid esophagus ranged from 1 to 20 (mean 7; median 7) and those obtained from the distal esophagus ranged from 1 to 18 (mean 6; median 5). There was no significant difference between the mean number of EOS/HPF from the mid (26) and lower (25) esophagus or between the mean peak number of EOS/HPF from the mid (69.1) and lower (60.4) esophagus. The probability of one, four, five, and six biopsy fragments containing >15 EOS/HPF was 0.63, 0.98, 0.99, and >0.99, respectively. From these data, at least four biopsy fragments should be submitted from the mid and/or proximal esophagus to optimize the chances of a positive diagnosis of EoE in populations not known to have undergone previous proton pump inhibitor therapy. However, the yield is not increased beyond six biopsy fragments. In order to morphologically exclude a diagnosis of reflux esophagitis as the cause of intraepithelial eosinophilia, distal esophageal biopsies, if obtained, must be accompanied by more proximal biopsies (i.e., mid esophagus or higher).

A case of Strongyloides hyperinfection syndrome

Strongyloides stercoralis , a parasitic nematode capable of autoinfection, causes asymptomatic infection in an immunocompetent host. However, in patients with immunosuppressed states it can cause hyperinfection and disseminated strongyloidiasis, which have high mortality rates. We report a case of the strongyloid hyperinfection syndrome in a 67-year-old female, who was immunosuppressed, on steroid therapy for idiopathic thrombocytopenic purpura (ITP), which was diagnosed on demonstration of larvae of strongyloides in the gastric mucosal biopsy. Her condition worsened by the time of diagnosis and she succumbed to her illness. The treatment options include ivermectin alone or with albendazole or thiabendazole. Atypical and fatal presentations of common asymptomatic infection are possible in immunosuppressed patients.

Analysis of Gene Mutations Associated with Antibiotic Resistance inHelicobacter pyloriStrains Isolated from Korean Patients

3 , Wonju, Korea Background/Aims: This study aims to identify the gene mutation pattern associated with antibiotic resistance for mainly used anti- biotics in Helicobacter pylori strains isolated from Koreans. Materials and Methods: Seventy-one H. pylori strains were isolated from gastric mucosal biopsy specimens. The specimens were cultivated and the resistance to 5 antibiotics were assessed by using agar gel dilution method. DNA sequencing was carried out to detect the resistance-related gene mutations. Results: A point mutation at A2143G of 23S rRNA was observed in all of the clarithromycin resistant strains, but tetracycline re- sistant strains were not found. Substitution N562Y in penicillin binding protein 1 were observed in an amoxicillin resistant strain (minimum inhibitory concentration (MIC) 2.0μg/mL). Eleven (57.8%) out of 19 levofloxacin resistant strains showed amino acid substitution at N87K (8 strains), N87I, A88V and D91N in GyrA. The truncation in rdxA was detected in 8 (25.0%) out of 32 metro- nidazole resistant strains. Two out of the 7 patients who failed in first-line treatment of clarithromycin and amoxicillin showed A2143G mutation. Conclusions: 23S rRNA mutation is closely related to the failure of eradication, however, the fact that five people who have no gene mutation failed eradication implies that other factors are related. As MIC levels in clarithromycin and levofloxacin resistance strains are getting higher, their appropriate gene mutation is more correlated. (Korean J Helicobacter Up Gastrointest Res 2014;14:95-102)

English

Since the discovery of Helicobacter pylori in 1983 by Robin Warren and Barry Marshall, the diagnosis and treatment of upper gastrointestinal disease have changed greatly. As infection with H. pylori is the strongest known risk factor for gastric cancer, that is why our study was undertaken in our surgery department to establish the role of H. pylori in patients of gastric cancer in Southern Odisha. Total 70 patients of gastric cancer as cases and 32 controls were studied. H. pylori infection status in all cases and controls was assessed by serological test, rapid urea broth test and histopathological examination of the gastric mucosal biopsy specimens. H. pylori infection was positive in 64 cases of cancer stomach (91.43%) and 24 patients were positive in the control group (75%). The odds ratio was estimated to be 3.56 and p. value was found to be < 0.02.

Decreased expression of gastrokine 1 in gastric mucosa of gastric cancer patients.

To investigate the expression of gastrokine 1 (GKN1) in normal gastric mucosa, precancerous lesions and gastric cancer tissues, and to analyse its correlations with tumour site and pathological pattern. Thirty gastric cancer patients (12 cases of diffuse type and 18 cases of intestinal type), 13 atrophic gastritis patients and 15 healthy volunteers with almost normal gastric mucosa (superficial gastritis) were enrolled in this study. Helicobacter pylori (H. pylori) infection was examined in all subjects. All gastric mucosa biopsy specimens were obtained. Cancer-adjacent specimens were taken from corresponding gastric cancer patients. Immunohistochemistry and real-time PCR were performed to determine the expressions of the GKN1 protein and mRNA, respectively. H. pylori infection had no significant association with age, gender, tumour site or pathological pattern in all subjects. Compared with the superficial gastritis and atrophic gastritis groups, the expression of GKN1 protein (P = 0.011) and mRNA (P < 0.001) in gastric cancer was significantly decreased. The GKN1 mRNA level in diffuse type gastric cancer was significantly lower than in intestinal type gastric cancer (0.296 ± 0.076 vs 0.525 ± 0.164, P < 0.001). Compared with almost normal gastric mucosa, GKN1 expression in the gastric mucosa of gastric cancer patients is decreased; this is associated with progression and prognosis of gastric cancer.

Different Gastric Mucosa and CagA Status of Patients in India and Japan Infected with Helicobacter pylori

Despite similar incidence of Helicobacter pylori infection, the frequency of gastric cancer is sevenfold higher in Japan than in India. The objective of this work was to define differences in H. pylori-induced gastritis and to identify the bacterial virulence factors involved. We prospectively enrolled 353 consecutive patients who underwent endoscopy and received three gastric biopsies in Tokyo, Japan, and Hyderabad, India. Immunohistochemistry against H. pylori and East Asian CagA and hematoxylin-eosin and Giemsa stain were used to examine gastric mucosal biopsy specimens. Histological scores were assessed in accordance with the updated Sydney System. Subjects with H. pylori infection were matched by age and sex to compare histopathology and bacterial virulence. Sixty patients infected with H. pylori were prospectively selected. Median histological scores for neutrophil and mononuclear cell infiltration and for atrophy were significantly higher in Japan than in India (neutrophils 4.0 vs 3.0, p < 0.01; mononuclear cells 5.0 vs 4.5, p = 0.03; atrophy 3.0 vs 2.0, p < 0.01, respectively). Scores for H. pylori density and intestinal metaplasia were also higher in Japan, albeit without statistical significance (H. pylori 5.0 vs 3.0, p = 0.08; intestinal metaplasia 0.0 vs 0.0, p = 0.08). Prevalence of East Asian CagA-positive H. pylori was significantly higher in Japan (73.3 vs 0.0 %, p < 0.01). The significantly higher prevalence of histologically severe gastritis and East Asian CagA in patients from Japan with H. pylori infection may be involved in the pathogenesis of gastric cancer.

Abstract C13: Population-based evaluation of serum pepsinogen, anti-H. pylori IgG antibody and gastrin-17 tests for gastric cancer screening

Abstract Objective: This study evaluated the role of multiple serological tests (including serum pepsinogen I (PGI), PGII, PGI/II ratio, anti-H. pylori IgG antibody, and gastrin-17 tests) individually and in combination in gastric cancer (GC) screening. Design: Data were from the Zhuanghe Gastric Cancer Study, a 15-year, population-based endoscopic, gastric diseases screening program in northern China. From 1997 to 2011, esophagogastroduodenoscopies with gastric mucosal biopsies were conducted on 10,693 participants. All serum biomarkers were measured using ELISA, and gastric biopsies were evaluated using standardized criteria. Logistic regression was used to calculate odds ratios (OR) with 95 percent confidence intervals (95% CI) and produce receiver operator characteristic (ROC) curves with corresponding c statistics. In addition, results were replicated in an independent hospital-based population. Results: PGI/II ratio monotonically decreased as gastric mucosa progresses from normal mucosa to precancerous conditions, and to GC, and a low PGI/II ratio (≥ 6.6) was associated with an increased risk of prevalent GC (OR = 2.34, 95% CI: 1.62, 3.39). PGI/II ratio individually or in combination with PGI, PGII, anti-H. pylori IgG antibody and gastrin-17 provided the same c statistic of 0.62 for screening for GC. PGI, PGII, anti-H. pylori IgG antibody or gastrin-17 tests individually provided c statistics less than or equal to 0.55. For identifying abnormal gastric conditions including GC, the five serological tests in combination provided adequate discriminatory performance (c = 0.77), and yielded a sensitivity of 84.0% and specificity of 50.0%. The results from the independent hospital-based population were similar. Conclusion: Our results suggest that serum PGI, PGII, PGI/II ratio, anti-H. pylori IgG and gastrin-17 tests can be used as prescreening tests for patients at high risk for GC. Citation Format: Huakang Tu, Liping Sun, Yuehua Gong, Qian Xu, Qi Long, Roberd Bostick, Yuan Yuan. Population-based evaluation of serum pepsinogen, anti-H. pylori IgG antibody and gastrin-17 tests for gastric cancer screening. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr C13.

Helicobacter Pylori HP(2–20) Induces Eosinophil Activation and Accumulation in Superficial Gastric Mucosa and Stimulates VEGF-α and TGF-β Release by Interacting with Formyl-Peptide Receptors

Eosinophils participate in the immune response against Helicobacter pylori, but little is known about their role in the gastritis associated to the infection. We recently demonstrated that the Hp(2-20) peptide derived from H. pylori accelerates wound healing of gastric mucosa by interacting with N-formyl peptide receptors (FPRs) expressed on gastric epithelial cells. The aim of the present study was to investigate whether eosinophils play a role in the repair of gastric mucosa tissue during H. pylori infection. Immuno-histochemistry and transmission electron microscopy were used to detect eosinophils in gastric mucosal biopsies. Eosinophil re-distribution occurred in the gastric mucosa of H. pylori-infected patients: their density did not change in the deep mucosal layer, whereas it increased in the superficial lamina propria just below the foveolar epithelium; eosinophils entered the epithelium itself as well as the lumen of foveolae located close to the area harboring bacteria, which in turn were also engulfed by eosinophils. The H. pylori-derived peptide Hp(2-20) stimulated eosinophil migration through the engagement of FPR2 and FPR3, and also induced production of VEGF-A and TGF-beta, two key mediators of tissue remodelling. We also demonstrate that Hp(2-20) in vivo induced eosinophil infiltration in rat gastric mucosa after injury brought about by indomethacin. This study suggests that eosinophil infiltrate could modulate the capacity of gastric mucosa to maintain or recover its integrity thereby shedding light on the role of eosinophils in H. pylori infection.

Determination of relative frequency of eosinophils and mast cells in gastric and duodenal mucosal biopsies in adults with non-ulcer dyspepsia.

To determine eosinophil and mast cell populations in gastric and duodenal mucosal biopsies of adults with nonulcer dyspepsia (NUD) as compared to non-dyspeptic adults. A case control study. Shahid Sadoughi University of Medical Sciences, Yazd, Iran, from January 2010 to June 2011. A total of 52 (25 non-ulcer dyspeptic patients as case and 27 non-dyspeptic patients as control) patients underwent endoscopy. All patients had a minimum of 2 forceps biopsies obtained from stomach and duodenum. Routine histological evaluation was performed and additionally evaluated to determine eosinophil and mast cell counts. The statistical analysis was performed on SPSS version 17.0, using Mann-Whitney test with significance at p < 0.05. The mean age in the case and control groups was 31.72 ± 12.17 and 35.74 ± 12.42 years respectively. The median eosinophil density in gastric mucosa in case group was 5.0 (ranging from 1 to 20) and 4.0 in control group (ranging from 0 to 16; p = 0.140). The median eosinophil density in duodenal mucosa in case group was 16.0 (ranging from 2 to 24) and 13 in control group (ranging from 2 to 45; p = 0.147). The median mast cell density in gastric mucosa in case group was 4.0 (ranging from 0 to 33) and 4.0 in control group (ranging from 0 to 26; p = 0.827). The median mast cell density in duodenal mucosa in case group was 4.0 (ranging from 0 to 31) and 3.0 in control group (ranging from 1 to 23; p = 0.704). The frequency of Helicobacter pylori infection in both the groups was similar. Although there were not statistically significant differences in eosinophil and mast cell densities between case and control groups, there was a trend toward mild eosinophilia in gastric and duodenal mucosa. The specific role of eosinophils and mast cells in NUD is yet to be completely defined.

Iron Deficiency Anemia Due to Lymphocytic Gastritis With Helicobacter pylori Infection in Childhood

Lymphocytic gastritis (LG) is a chronic inflammatory process of poorly understood pathogenesis. We report the case of a 12-year-old premenstrual girl with refractory iron deficiency anemia in which the oral iron absorption challenge suggested iron malabsorption. Laboratory studies ruled out celiac disease and autoimmune gastritis, and carbon-13 urea breath test for Helicobacter pylori was also negative. Upper endoscopy with gastric body and antral mucosa biopsies revealed a LG with focal intestinal metaplasia and H. pylori infection. H. pylori eradication was undertaken with success and 3 months later her hematologic parameters normalized. Histologic reevaluation showed disappearance of LG. This case shows that investigation of malabsorption disease in the presence of refractory iron deficiency anemia can lead to the diagnosis of important gastric diseases, even in the absence of gastrointestinal symptoms. This nonceliac child was diagnosed with a severe histopathologic pattern of LG, with potential risk of malignant transformation, which was completely reverted with adequate H. pylori eradication treatment.

Gastric Helicobacter pylori infection is associated with adverse metabolic traits in severely obese subjects

Asian studies have reported on an association of Helicobacter pylori (Hp) infection with insulin resistance (IR) in normal-weight subjects. Whether such an association likewise exists in European subjects with severe obesity was questioned. To address this question, 370 severely obese patients from our database were identified, who had undergone a gastroscopy with a histological examination of gastric mucosal biopsies and a concurrent assessment metabolic blood parameters as a standard examination before bariatric surgery. Seventy-five (20.3%) of the subjects displayed a histologically proven Hp infection (Hp+). Sex distribution, age, and body mass index of Hp+ subjects did not differ from that of the subjects with no Hp infection (Hp-; all P > 0.293), but Hp+ subjects were significantly smaller (P = 0.006). Fasting glucose, insulin, high-sensitive C reactive protein, and alanine aminotransferase levels as well as calculated indices of IR (i.e., HOMA-IR, QUICKI) did not differ between Hp+ and Hp- subjects (all P > 0.42). However, Hp+ subjects showed significantly higher triglyceride levels and a higher total chloesterol-to-HDL ratio but lower sex-hormone binding globulin (SHGB) levels than Hp- subjects (all P ≤ 0.05). While our results obtained in European severely obese patients do not provide evidence for an enhanced IR state associated with gastric Hp infection, they suggest that the presence of the bacterium in gastric biopsies is associated with an adverse lipid profile and reduced SHGB levels.

Preoperative Nutritional Deficiencies in Severely Obese Bariatric Candidates are not Linked to Gastric Helicobacter pylori Infection

Severely obese subjects have been found to show a high prevalence of distinct nutritional deficiencies even without any bariatric intervention but the underlying reasons remain obscure. We tested the hypothesis that gastric Helicobacter pylori infection is associated with increased nutritional deficiency rates. Taking advantage of our large database, we identified 404 patients who had undergone a gastroscopy--as a standard diagnostic assessment before bariatric surgery--along with a histological examination of gastric mucosal biopsies with concurrent nutritional blood measurements. Eighty-five (21 %) of the obese patients included in the study displayed a gastric H. pylori infection. Sex distribution, age and body mass index did not differ between H. pylori+ and H. pylori- patients (P > 0.29). Referring to nutritional markers, neither serum levels of total protein, albumin, calcium, phosphate, magnesium, ferritin, zinc, copper, vitamin B12, folate and 25-OH vitamin D3 nor respective deficiency rates differed between the H. pylori+ and H. pylori- patients group (all P > 0.13). Overall, 49.5 % of the bariatric candidates displayed at least one nutritional deficiency. Our data confirm previous reports on high prevalences of nutritional deficiencies in severely obese subjects. However, they do not provide evidence for a contributing role of gastric H. pylori infection to these nutritional alterations.

Gastric Sarcoidosis: A Rare Clinical Presentation

Gastrointestinal (GI) sarcoidosis is a very rare disease, which clinically presents along with systemic disease or as an isolated finding. Gastric sarcoidosis is the most common form of GI sarcoidosis. Symptomatic gastric sarcoidosis is rare and only few case reports have been described in the literature with well-documented histological evidence of noncaseating granulomas. We present an interesting case of gastric sarcoidosis in a 39-year-old Caucasian man with symptoms of epigastric pain and profound weight loss. His endoscopic gastric mucosal biopsies revealed noncaseating granulomas consistent with gastric sarcoidosis. Treatment with oral steroids alleviated his symptoms with no recurrence in 2 years. Gastric sarcoidosis should be considered in patients with history of sarcoidosis and GI symptoms.

Cultural characteristics and antibiotic susceptibility pattern of Helicobacter Pylori isolated from dyspepsia patients

Helicobacter pylori consist in a helical shaped Gram-negative bacterium, approximately 3 micrometers long with a diameter of approximately 0.5 micrometers. It has 4-6 flagella. It is microaerophilic and tests positive for oxidase, catalase and urease. With its flagella, the bacterium moves through the stomach lumen and drills into the mucus gel layer of the stomach. In humans, H. pylorihave been associated with peptic ulcers, chronic gastritis, duodenitis and stomach cancer. It is widely believed that in the absence of treatment, H. pyloriinfection, once established in its gastric niche, persists for life. The aim of this research is to study the cultural characteristics and antibiotic susceptibility pattern of H. pyloristrains isolated from southwest Nigeria. The cultural characteristics and antibiotic susceptibility pattern of Helicobacter pylori strains isolated from gastric mucosal antral biopsy specimens collected from 43 of 52 dyspepsia patients in the University College Hospital Ibadan, Oyo State, Nigeria, were determined using standard microbiological methods for Helicobacter pylori isolation. The 43 isolates were subjected to 23 different antibiotics and each of the antibiotics demonstrated a variable degree of activity against the isolates. Among the antibiotics to which the organism was most susceptible are: ofloxacin (30 µg) 100% activity, ciprofloxacin (5 µg) 97.67% activity, gentamicin (120 µg) 95.35 activity, amikacin (30 µg), kanamycin (30 µg) and chloramphenicol (30 µg) each 90.70% activity, clarithromycin (15 µg) 93.02, while the less active antibiotics are: augmentin (30 µg) 23.26% active, amoxycillin (25 µg) and metronidazole (50 µg) each 27.91% active and clindamycin (2 mg) 30.23% active. From the result of the antibiotic susceptibility pattern of the strains of the organism, 95.35% of the total isolates are multi drug resistant. Resistance was developed to, among others, augmentin (30 µg), amoxycillin (25 µg), metronidazole (50 µg) and clindamycin (2 mg).

Liver–Intestine-Cadherin Is a Sensitive Marker of Intestinal Differentiation During Barrett’s Carcinogenesis

BackgroundHistopathologic differentiation between the stages of Barrett’s carcinogenesis is often challenging. Liver–intestine (LI)-cadherin, an intestine-specific marker, is involved in intestinal metaplasia development in gastric and colon cancers and could be of value in diagnosis and differentiation.AimsTo examine the expression of LI-cadherin in the sequence of Barrett’s carcinogenesis and to evaluate its association with clinicopathological data.MethodsLI-cadherin expression was immunohistologically investigated, by use of anti-CDH17 antibody, in gastric mucosa (GM) biopsies taken from the cardia (n = 9), in Barrett’s esophagus (BE) without intraepithelial neoplasia (without IEN) (n = 9) and BE with low-grade IEN (n = 11), and in esophageal adenocarcinoma (ADC) (n = 13).ResultsThe immunoreactivity score was highest in adenocarcinoma (mean IRS = 4.0), and dropped gradually from BE with IEN and BE without IEN (mean IRS = 2.0) to cardia mucosa (IRS = 0). Similarly, the intensity of staining and the percentage of positive cells increased during the sequential stages of BE carcinogenesis. Comparative analysis showed that LI-cadherin expression was significantly different between cardiac epithelium and ADC. Also, percentage of positive cells in GM was significantly different from that in BE with IEN. LI-cadherin IRS was lower for tumors with poor differentiation than for moderately differentiated tumors, but the difference was not statistically significant.ConclusionsLI-cadherin is a sensitive marker of intestinal metaplasia and can be helpful for early histologic diagnosis of Barrett’s esophagus; it is, however, not significantly different between BE with and without IEN, and cannot be used to distinguish between these.

Esophageal Polyp Arising from a Gastric Inlet Patch Causing Dysphagia

Purpose: Heterotopic gastric mucosa is usually an aymptomatic finding. We present a 58-year-old male who was admitted for nausea, vomiting and coffee ground emesis. He also noted intermittent solid food dysphagia, heartburn and epigastric pain. His history was positive for diabetes, end stage renal disease (ESRD) on hemodialysis, hypertension and chronic alcohol use. Physical exam was positive for epigastric tenderness, mild dehydration and hypotension which stabilized with medical resuscitation. Endoscopy revealed two salmon colored patches of columnar appearing epithelium in the proximal esophagus suggestive of gastric inlet patches. There was a large, 1 cm, semipedunculated esophageal polyp arising from one of these patches. In addition, there was extensive erosive esophagitis seen in the distal and middle esophagus. The gastric mucosa appeared erythematous. Biopsies from the polyp confirmed it to consist of gastric cardia type mucosa with hyperplastic foveolar epithelium and inflammatory cells with no evidence of squamous epithelium. The salmon colored mucosal patches were positive for gastric cardia type of epithelium with evidence of ulcerative esophagitis. The inflamed esophageal mucosa showed changes of reflux esophagitis. Gastric mucosal biopsy was suggestive of non specific reactive gastropathy. The patient was started on high dose proton pump inhibitor therapy and other resuscitative measures were instituted. Plan was to repeat endoscopy and an EUS after 6 weeks of treatment with PPI. However, after resolution of his symptoms, the patient deferred further invasive work-up. Esophageal polyps are a rare occurrence and may be of diverse histopathologic types. The class of hyperplastic esophageal polyps is usually found in relation to GERD, at the GE junction and is histologically characterized by proliferation of hyperplastic gastric-type foveolar epithelium, hyperplastic squamous epithelium, or an admixture of the two linings with variable inflammatory infiltrate. This case illustrates a very rare occurrence of an esophageal polyp arising from gastric inlet patch and causing symptomatic dysphagia.

Assessment of Helicobacter pylorieradication in patients on NSAID treatment

BackgroundIn this post-hoc analysis of a randomized, double blind, placebo controlled trial, we measured the sensitivity and specificity of Helicobacter pylori IgG-antibody titer changes, hematoxylin and eosin (H&E) stains, immunohistochemical (IHC) stains and culture results in NSAID using patients, following H. pylori eradication therapy or placebo.Methods347 NSAID using patients who were H. pylori positive on serological testing for H. pylori IgG-antibodies were randomized for H. pylori eradication therapy or placebo. Three months after randomization, gastric mucosal biopsies were taken for H. pylori culture and histological examination. At 3 and 12 months, blood samples were taken for repeated serological testing. The gold standard for H. pylori infection was based on a positive culture or both a positive histological examination and a positive serological test. Sensitivity, specificity and receiver operating curves (ROC) were calculated.ResultsH. pylori eradication therapy was successful in 91% of patients. Culture provided an overall sensitivity of 82%, and 73% after eradication, with a specificity of 100%. Histological examination with either H&E or IHC stains provided sensitivities and specificities between 93% and 100%. Adding IHC to H&E stains did not improve these results. The ROC curve for percent change in H. pylori IgG-antibody titers had good diagnostic power in identifying H. pylori negative patients, with an area under the ROC curve of 0.70 (95 % CI 0.59 to 0.79, P = 0.085) at 3 months and 0.83 (95% CI 0.76 to 0.89, P < 0.0001) at 12 months. A cut-off point of at least 21% decrease in H. pylori IgG-antibody titers at 3 months and 58% at 12 months provided a sensitivity of 64% and 87% and a specificity of 81% and 74% respectively, for successful eradication of H. pylori.ConclusionsIn NSAID using patients, following H. pylori eradication therapy or placebo, histological examination of gastric mucosal tissue biopsies provided good sensitivity and specificity ratios for evaluating success of H. pylori eradication therapy. A percentual H. pylori IgG-antibody titer change has better sensitivity and specificity than an absolute titer change or a predefined H. pylori IgG-antibody titer cut-off point for evaluating success of H. pylori eradication therapy.

Abstracts and Case Studies From the College of American Pathologists 2012 Annual Meeting (CAP '12)

Abstracts and Case Studies From the College of American Pathologists 2012 Annual Meeting (CAP '12)

Upregulation and inhibition of the nuclear translocation of Oct4 during multistep gastric carcinogenesis

Gastric cancer is the fourth most commonly diagnosed malignancy and the second leading cause of cancer-related mortality worldwide. Recent research suggests that tissue stem cells and the self renewal transcription factor, octamer-binding transcription factor4 (Oct4), could be involved in the development of certain tumors. The aim of this study was to investigate the expression pattern of Oct4 in normal human stomach and during multistep gastric carcinogenesis. Pyloric antral mucosal tissues were obtained from consenting individuals undergoing endoscopy (due to upper gastrointestinal symptoms) and gastrectomy (due to pyloric antral adenocarcinoma). Some tissue samples were processed to assemble an array of tissue sections representing multistep carcinogenesis and probed using anti-Oct4 antibodies and lectins specific for α-L-fucose or N-acetyl-D-glucosamine. Some tissue samples were processed for subcellular fractionation and western blot analysis using the same antibodies. The results revealed that Oct4-expressing cells were found in the proliferative cell compartment of the pit-gland units of microscopically normal gastric mucosal biopsies. Mucosal tissues with evidence of severe gastritis, metaplastic/dysplastic transformation and gastric cancer showed a significant increase in the expression of Oct4 (the labeled area increased from 2% in the control to 6 and 16% in the gastritis and cancerous tissues, respectively), suggesting a role for Oct4 in the early stages of cancer development. Furthermore, the data revealed an alteration in the subcellular distribution of Oct4, possibly due to the inhibition of cytoplasm-to-nucleus translocation during carcinogenesis. In conclusion, this study demonstrates an alteration in the expression pattern and nuclear translocation of Oct4 during gastric carcinogenesis and may be helpful in designing new modalities for the early detection and/or therapy of gastric cancer.

Population-based gastric cancer screening in Zhuanghe, Liaoning, from 1997 to 2011

To investigate the feasibility of gastric cancer screening for the susceptible population in the high-risk areas of China and to optimize the screening programme. By using the two-round screening method i.e. serum pepsinogen test combined with gastric mucosa biopsy, large-scale population screening programs were carried out in Zhuanghe, Liaoning province. All adults or residents above 35 years old with a positive family history of gastric cancer or gastrointestinal symptoms were targeted. Three large-scale population screenings were developed over the past 15 years. All together, 13078 participants accepted the two-round screening, and 108 gastric cancer cases were detected. Among them, the detection rate of early gastric cancer was 56.82%, 51.22% and 82.61%, respectively. The pathologically confirmed gastric cancer cases were immediately arranged to have early surgical treatment, and meanwhile, the follow-up files for the patients were established. With a consecutive and regular 10-year postoperative follow-up, the 5-year survival rate for these early gastric cancer patients reached 90.48%. Effectiveness and health economic evaluation confirmed that there are good specificity and sensitivity for the two round screening programs. It is cost-effective. As the primary screening method serum PG test can improve the screening examination rate and concentrate the gastric cancer risk populations. It is feasible to develop the gastric cancer screening program among the susceptible population in high-risk areas in our country, and the two-round screening method is of practical value. Research for early detection of gastric cancer should be further enhanced, and multidisciplinary and multicenter cooperation should be organized. It is necessary to extend the implementation the gastric cancer screening and to further improve the early detection programme, in order to make a breakthrough based on the present practice.