Mucosal microbial microenvironment in early gastric neoplasia and non-neoplastic gastric disease.

BACKGROUND AND AIM: The biological characterization of microbial environment in early gastric cancer (EGC), other than Helicobacter pylori, is limited. This study aimed to explore the microbial microenvironment in chronic gastritis (CG), fundic gland polyps (FGPs), low-grade intraepithelial neoplasia (LGIN), and EGC. METHODS: 16S-rRNA gene sequencing and bioinformatic analysis were performed on 63 individuals with 252 mucosal biopsies or endoscopic submucosal dissection margin samples from endoscopy. RESULTS: The microbiota in gastric LGIN functions analogously to EGC in terms of functional prediction. Neoplastic lesions showed a significant difference to CG or FGPs in beta diversity of the microbiota. Bacteria genera including Paracoccus, Blautia, Barnesiella, Lactobacillus, Thauera, Collinsella were significantly enriched in gastric neoplastic mucosa (LGIN and EGC) compared with non-neoplastic tissues (CG and FGPs). While Pseudomonas and Kingella were depleted in neoplastic tissues. FGPs showed a distinctive microbial network system that negatively interacted with Helicobacter. CONCLUSIONS: In terms of the mucosal microbial microenvironment, gastric LGIN and EGC showed no significant difference as early neoplastic lesions. We observed a coordinated microbial microenvironment that correlated negatively with Helicobacter.

Characterization of Helicobacter pylori-Naïve Early Gastric Cancers.

AIM: Helicobacter pylori-naïve gastric cancers(GCs) have not been well documented. We aimed to characterize early H. pylori-naïve GCs. SUBJECTS AND METHODS: Of 666 patients with GC resected by endoscopic submucosal dissection, H. pylori-naïve patients were extracted according to the definition: no H. pylori eradication history, negative for serum H. pylori-antibody and current H. pylori-infection tests, and no gastric atrophy by pepsinogen (PG) test, endoscopy, and histology. RESULTS: It was found that 16 GCs were H. pylori-naïve, and classified into undifferentiated and differentiated type adenocarcinoma. All 9 undifferentiated type GCs were pale, depressed, mucosal pure signet ring cell adenocarcinoma except one of them and 7 differentiated type GCs were classified into 3 fundic gland type GCs and 4 foveolar type GCs. All fundic gland type GCs positive for PG-1 were cardia small submucosal tumor (SMT)-like protrusions with dilated vessels on the surface. All 4 foveolar type GCs were composed of dysplastic clear cells resembling foveolar epithelium, negative for PG-1 but positive for mucin 6 (MUC6) and MUC5AC. Endoscopically, all were laterally spreading elevations with papillary or villous surface. CONCLUSIONS: H. pylori-naïve GCs were infrequent at 2.5%, and classified into 3 types: a small pale depression of signet ring cell adenocarcinoma, a small SMT-like protrusion of fundic gland type GC, and a large laterally spreading elevation of foveolar type GC.

CD44 plays a functional role in Helicobacter pylori-induced epithelial cell proliferation.

The cytotoxin-associated gene (Cag) pathogenicity island is a strain-specific constituent of Helicobacter pylori (H. pylori) that augments cancer risk. CagA translocates into the cytoplasm where it stimulates cell signaling through the interaction with tyrosine kinase c-Met receptor, leading cellular proliferation. Identified as a potential gastric stem cell marker, cluster-of-differentiation (CD) CD44 also acts as a co-receptor for c-Met, but whether it plays a functional role in H. pylori-induced epithelial proliferation is unknown. We tested the hypothesis that CD44 plays a functional role in H. pylori-induced epithelial cell proliferation. To assay changes in gastric epithelial cell proliferation in relation to the direct interaction with H. pylori, human- and mouse-derived gastric organoids were infected with the G27 H. pylori strain or a mutant G27 strain bearing cagA deletion (∆CagA::cat). Epithelial proliferation was quantified by EdU immunostaining. Phosphorylation of c-Met was analyzed by immunoprecipitation followed by Western blot analysis for expression of CD44 and CagA. H. pylori infection of both mouse- and human-derived gastric organoids induced epithelial proliferation that correlated with c-Met phosphorylation. CagA and CD44 co-immunoprecipitated with phosphorylated c-Met. The formation of this complex did not occur in organoids infected with ∆CagA::cat. Epithelial proliferation in response to H. pylori infection was lost in infected organoids derived from CD44-deficient mouse stomachs. Human-derived fundic gastric organoids exhibited an induction in proliferation when infected with H. pylori that was not seen in organoids pre-treated with a peptide inhibitor specific to CD44. In the well-established Mongolian gerbil model of gastric cancer, animals treated with CD44 peptide inhibitor Pep1, resulted in the inhibition of H. pylori-induced proliferation and associated atrophic gastritis. The current study reports a unique approach to study H. pylori interaction with the human gastric epithelium. Here, we show that CD44 plays a functional role in H. pylori-induced epithelial cell proliferation.

In vitro antimicrobial susceptibility of Helicobacter pylori to nine antibiotics currently used in Central Italy.

OBJECTIVE: Helicobacter pylori expresses an increased resistance in respect to antimicrobials currently used in therapy. The aim of this study was to evaluate the antimicrobial profiles of H. pylori isolates to nine conventional antibiotics used in a Central Region (Abruzzo) of Italy. MATERIALS AND METHODS: Biopsies were taken from antrum and fundus of 112 adult and 3 children with Urea Breath Test positive with dyspeptic symptoms and analyzed for H. pylori culture and antibacterial activity. Antimicrobial susceptibility tests were performed for clarithromycin, metronidazole, levofloxacin, moxifloxacin, ciprofloxacin, tetracycline, amoxicillin, ampicillin, and rifabutin by a modified agar dilution susceptibility test. RESULTS: Bacterial culture was successful in 100 out of 115 patients. Helicobacter pylori strains were isolated from 98 antrum and 83 fundus samples. The rate of recovery of H. pylori strains was 90.50% (181/200). The percentages of resistance were as follows: clarithromycin 72.44% antrum, 72.28% fundus; metronidazole 34.69% antrum, 42.16% fundus; levofloxacin 42.85% antrum, 53.01% fundus; moxifloxacin 37.35% antrum, 46.57% fundus; ciprofloxacin 39.47% antrum, 44.28% fundus; tetracycline 2.63% antrum, 2.85% fundus; amoxicillin 1.02% antrum, 1.20% fundus; ampicillin 0% antrum and fundus and rifabutin 0% antrum, 1.20% fundus. A total of 35 subjects harbored multi-resistant strains. CONCLUSIONS: This study underlines the high rate of resistance to clarithromycin, metronidazole and quinolones, which may reflect an overuse of them. Culture and susceptibility test, should be performed to prevent the emergence of multi-resistance and to assess an efficacious regimen.

Helicobacter pylori and gastroesophageal reflux disease.

PURPOSE OF REVIEW: The purpose of the review is to discuss key studies conducted on the intriguing relationship between Helicobacter pylori and gastroesophageal reflux disease. RECENT FINDINGS: Epidemiological studies have repeatedly described a negative association between H. pylori infection and erosive esophagitis, Barrett's esophagus, and esophageal adenocarcinoma, but not between H. pylori and gastroesophageal reflux disease symptoms. Especially, infection with CagA-positive strains appears to protect the distal esophagus by causing fundic gland atrophy and impaired gastric acid secretion. Although earlier reports suggested the development of erosive esophagitis after H. pylori eradication, more recent studies discuss that H. pylori eradication usually does not have an important clinical impact on gastroesophageal reflux disease. SUMMARY: Gastric atrophy is the most widely accepted mechanism by which the distal esophagus is protected from abnormal acid exposure in patients with H. pylori infection. The clinical impact of H. pylori infection on the prevalence of erosive esophagitis and Barrett's esophagus remains a matter of debate. In areas with a high prevalence of H. pylori-induced atrophic gastritis, the protection that this infection may afford against gastroesophageal reflux disease is not comparable to the risk that H. pylori poses for the development of gastric cancer.

H. pylori acutely inhibits gastric secretion by activating CGRP sensory neurons coupled to stimulation of somatostatin and inhibition of histamine secretion.

Acute Helicobacter pylori infection produces hypochlorhydria. The decrease in acid facilitates survival of the bacterium and its colonization of the stomach. The present study was designed to identify the pathways in oxyntic mucosa by which acute H. pylori infection inhibits acid secretion. In rat fundic sheets in an Ussing chamber, perfusion of the luminal surface with H. pylori in spent broth (10(3)-10(8) cfu/ml) or spent broth alone (1:10(5) to 1:10(0) final dilution) caused a concentration-dependent increase in somatostatin (SST; maximal: 200 ± 20 and 194 ± 9% above basal; P < 0.001) and decrease in histamine secretion (maximal: 45 ± 5 and 48 ± 2% below basal; P < 0.001); the latter was abolished by SST antibody, implying that changes in histamine secretion reflected changes in SST secretion. Both responses were abolished by the axonal blocker tetrodotoxin (TTX), the sensory neurotoxin capsaicin, or the CGRP antagonist CGRP8-37, implying that the reciprocal changes in SST and histamine secretion were due to release of CGRP from sensory neurons. In isolated rabbit oxyntic glands, H. pylori inhibited basal and histamine-stimulated acid secretion in a concentration-dependent manner; the responses were not affected by TTX or SST antibody, implying that H. pylori can directly inhibit parietal cell function. In conclusion, acute administration of H. pylori is capable of inhibiting acid secretion directly as well as indirectly by activating intramural CGRP sensory neurons coupled to stimulation of SST and inhibition of histamine secretion. Activation of neural pathways provides one explanation as to how initial patchy colonization of the superficial gastric mucosa by H. pylori can acutely inhibit acid secretion.

Correlation between Helicobacter pylori infection and low-dose aspirin use on damage of the upper gastrointestinal tract.

BACKGROUND AND AIM: Low-dose aspirin (LDA), and Helicobacter pylori (HP) infection are considered the two primary causes of peptic ulceration. The interaction between HP infection and non-steroidal anti-inflammatory drugs is, however, a matter of considerable discussion and controversy. In this study, we investigated possible synergistic or negative interactions between HP infection and LDA in gastric mucosal lesions, according to lesion site. METHODS: The subjects were 120 patients attending the Cardiology Outpatients Department (average age, 67.1 ± 8.9 years; male : female ratio 2.9:1). Endoscopic findings were graded using the Modified Lanza score. Lesions were scored for the antral, body and fundal regions. Ulcers were defined as mucosal defects ≥ 5 mm in size. RESULTS: There were 55 HP-positive and 65 HP-negative subjects, and 91 subjects on LDA therapy. The gastric antral Lanza scores were HP(-) LDA(-): 0.2 ± 1.6, HP(-) LDA(+): 1.8 ± 1.5, HP(+) LDA(-): 0.3 ± 0.7, and HP(+) LDA(+): 0.5 ± 1.0. The gastric body and fundal Lanza scores were 0.0 ± 0.0, 0.8 ± 0.9, 0.4 ± 1.1, and 1.0 ± 1.5, respectively, and 0.1 ± 0.3, 0.5 ± 0.9, 0.1 ± 0.3, and 0.1 ± 0.3, respectively. Variance analysis of the correlation between HP infection and LDA by regional Lanza scores identified both HP infection and LDA use as factors that significantly influence the antral Lanza score. However, LDA was an aggressive factor, and HP infection a protective factor. In the gastric body, LDA was a non-significant, and HP infection a significant, aggressive factor. In the gastric fundus, neither HP infection nor LDA was a significant factor (LDA was an aggressive factor, and HP infection a protective factor). CONCLUSIONS: LDA had aggressive effects in all gastric lesions; on the other hand, HP infection had protective effects in the antrum and fundus in the stomach, and aggressive effects in the body in the stomach.

Prevalence of Helicobacter pylori vacA, cagA, iceA and oipA genotypes in Tunisian patients.

BACKGROUND: Distinct virulence factors of H. pylori have been described: the vaculating cytotoxin (vacA), the cytotoxin associated gene (cagA), the induced by contact with epithelium factor Antigen (iceA gene) and the outer membrane protein oipA. In Tunisia, there are no data regarding the pattern of H. pylori genotypes; therefore, this prospective and multicentre study was the first to be done in Tunisia and aimed to investigate the prevalence of the vacA, cagA, iceA and oipA genotypes of H. pylori isolates from Tunisian patients with peptic ulceration, gastric cancer, MALT lymphoma and gastritis. METHODS: H. pylori was cultured from endoscopic biopsies obtained from 281 Tunisian patients. The vacA alleles, cagA, iceA and oipA genotypes were determined by PCR. RESULTS: The vacA s1m1, s1m2 and s2m2 were respectively found in 10.7%, 12.5% and 45.6% of strains. The s2m1 genotype was not detected in our study. The cagA was found in 61.6% of isolates. The iceA1 and the iceA2 genotypes were respectively isolated in 60.2% and in 16% of strains. The oipA genotype was detected in 90.8% of strains. Considering the vacA and iceA genotypes, the presence of multiple H. pylori strains in a single biopsy specimen was found respectively in 31.4% and 23.8%. The comparison between strains isolated from antrum and fundus showed that Tunisian patients were infected with two or more strains of different cagA, vacA, iceA and oipA genotypes and the discordance was respectively in 9.6%, 4.6%, 8.9% and 8.5% of strains. CONCLUSION: Our results showed that in 46% (131 strains among 281), the H. pylori strains were highly virulent in relation of the three or four virulent factors they could carry. These finding were described before in the literature. Tunisian patients were colonized by one or multiple strains of H. pylori in the same time in relation of presence of vacA m1/m2 and iceA1/iceA2 in the same biopsy. The discordance between strains isolated from antrum and fundus was high, and it is in favour of multicolonization.

No association between gastric fundic gland polyps and gastrointestinal neoplasia in a study of over 100,000 patients.

BACKGROUND & AIMS: Fundic gland polyps (FGPs), the most common type of gastric polyps, have been associated with prolonged proton pump inhibitor therapy and an increased risk of colon cancer. The presence of FGPs has been inversely correlated with Helicobacter pylori infection. We evaluated the prevalence of H pylori-associated gastritis, colonic polyps, and carcinomas in subjects with and without FGPs. METHODS: We analyzed data collected from community-based endoscopy centers in 36 states (plus Washington DC and Puerto Rico) on patients who underwent esophagogastroduodenoscopy (EGD) and colonoscopy between April 2007 and March 2008. Of the 103,385 patients who underwent EGD during this time period, gastric biopsy samples were collected from 78,801 and colonic biopsies from 26,017. Slides of samples from Helicobacter-infected FGPs and FGPs with dysplasia were reviewed. RESULTS: FGPs were detected in 6081 patients (67.8% women). Helicobacter infection was present in less than 0.5% patients with FGPs and 13.0% of those without FGPs (odds ratio [OR], 29.05; 95% confidence interval [CI], 20.4-41.4; P < .0001). Colonic adenomas were detected in 42.3% of women with FGPs and 33.8% of those without (OR, 1.43; 95% CI, 1.26-1.63; P < .001); there was no significant difference in colonic adenomas between men with and without FGPs. CONCLUSIONS: Women had a higher prevalence of FGPs. FGPs were associated with gastroesophageal reflux disease symptoms, gastric heterotopia, hyperplastic colonic polyps (only in men), and colonic adenomas (only in women, especially those over 60 years of age). The presence of FGPs was inversely correlated with H pylori infection, active gastritis, and gastric neoplasia.

Sustained epithelial proliferation in a functionally irreversible fundic mucosa after Helicobacter pylori eradication.

BACKGROUND: We recently reported the expansion of the acid-secreting mucosa following Helicobacter pylori eradication with Congo red chromoendoscopy for a short-term follow-up of up to 7 months. We aimed to extend the observation period and to clarify the characteristic features of acid-secreting and non-acid-secreting mucosa. METHODS: In 24 H. pylori-positive patients with fundic atrophy, Congo red chromoendoscopy was performed prior to, 1 month, 7 months, and finally more than 2 years after the eradication. The areas of the acid-secreting mucosa were evaluated semiquantitatively. Two gastric biopsy specimens were taken from the acid-secreting and non-acid-secreting areas at the final chromoendoscopy and were subjected to histologic evaluation and immunohistochemistry for Ki-67 as a proliferation index. RESULTS: After a gradual increase in acid-secreting areas for up to 7 months after eradication, they further increased in 79% subjects between 7 months and the final observation at a mean follow-up of 62 months. However, there still existed non-acid-secreting mucosa in the fundic area in all subjects, indicating that the expansion of acid-secreting mucosa remained partial. Compared with the neighboring acid-secreting area, the non-acid-secreting area was characterized histologically by higher degrees of residual inflammation, mucosal atrophy, and intestinal metaplasia, and by sustained hyperproliferation as well. CONCLUSIONS: Functionally irreversible (non-acid-secreting) gastric mucosa after eradication was associated with extensive intestinal metaplasia and sustained hyperproliferation, suggesting that such mucosa still possesses malignant potential. Congo red chromoendoscopy may be useful for estimating the risk of subsequent development of gastric cancer following successful H. pylori eradication by determining the distribution of functionally irreversible mucosa.

Lewis antigen expression by Helicobacter pylori strains colonizing different regions of the stomach of individual patients.

The diversity in the expression of Lewis antigens (Le) of 226 single colonies of Helicobacter pylori isolated from four regions of the stomach of eight adults is shown. Le(y) was expressed more in strains colonizing antrum than in strains colonizing fundus, whereas Le(x) was more common in fundus strains. cagA(+) strains were more associated with Le-negative strains.

Clarithromycin resistance of Helicobacter pylori strains isolated from children' gastric antrum and fundus as assessed by fluorescent in-situ hybridization and culture on four-sector agar plates.

AIM: To assess validity of culture on four-sector agar plates and fluorescent in-situ hybridization (FISH) test, and clarithromycin resistance rate in Helicobacter pylori strains isolated from children in the last 10 years. METHODS: In the last 5 years, gastric biopsy specimens from antrum and fundus were taken from 89 consecutive children (median age 9 years) with H. pylori gastritis and from 21 controls. Culture was performed on 176 gastric biopsies (89 from antrum, 87 from fundus) on four-sector agar plates, and FISH test with DNA ProbeMix. After its validity was evaluated, FISH test was applied on additional 119 biopsies from 68 children (68 from the antrum, 51 from the fundus) stored in the Pathology archive in the previous 5 years. RESULTS: Culture was positive in 157 of 176 biopsies (sensitivity: 89.2%, 95% confidence interval (CI) 85-94). In 33 of 89 children (37%) resistant strains were found in one or both gastric sites. FISH test was positive in 148 of 176 biopsies from infected children (sensitivity 84.1%, 95%CI 79-89) and in none of 42 biopsies from controls (specificity 100%). When applied on archive biopsies, FISH test was positive in 96 of 119 (80.7%, 95%CI 74-88). Total children harboring resistant strains in the last 10 years, as assessed by FISH test, were 66 of 157 (42%). Mixed infection with both sensitive and resistant strains were found in 40 children (25%) and in 12 of them resistant strains were in the fundus only. CONCLUSIONS: Culture on four-sector agar plates and FISH test had a high sensitivity and specificity and showed co-presence of sensitive and resistant strains. In one-third of children with mixed infection, the resistant strains were in the fundus only. Clarithromycin resistance should be assessed in biopsies both from the antrum and the fundus, utilizing antral biopsies only can underestimate its prevalence.

Gastric adenocarcinoma of fundic gland type with signet-ring cell carcinoma component: A case report and review of the literature.

A depressed lesion was found at a gastric angle of 76-year-old Japanese woman by esophagogastroduodenoscopy. Four years prior, she was diagnosed with a Helicobacter pylori infection but no eradication was performed. The pathological diagnosis of biopsy specimens was signet-ring cell carcinoma. Endoscopic submucosal dissection (ESD) was performed. Histopathological examination of the ESD specimen revealed proliferation of well-differentiated tubular adenocarcinoma mimicking fundic gland cells at the deep layer of the lamina propria mucosae. These tumor cells expressed focally pepsinogen-I, diffusely MUC6, and scattered H+/K+ ATPase according to immunohistochemistry. Therefore, we diagnosed this tumor as gastric adenocarcinoma of fundic gland type (GA-FG). Adjacent to the GA-FG, proliferation of signet-ring cell carcinoma which diffusely expressed MUC 2 and MUC 5AC was observed. Intestinal metaplasia was focally observed in the surrounding mucosa of the signet-ring cell carcinoma. To the best of our knowledge, this is the first case report of GA-FG with a signet-ring cell carcinoma component. The origin of signet-ring cell carcinoma, i.e., whether it accidentally arose from a non-neoplastic mucosa and coexisted with the GA-FG or dedifferentiated from the GA-FG is unclear at present. We expect the accumulation of similar cases and further analysis to clarify this issue.

Lectin binding patterns in normal, dysplastic and Helicobacter pylori infected gastric mucosa.

AIM: To analyze the glycoprotein binding sites of the gastric mucosa and its secreted mucus using lectin histochemistry in patients with chronic non-atrophic gastritis (CNAG) associated or not-associated with Helicobacter pylori infection with or without dysplasia. MATERIALS AND METHODS: In order to identify the areas with glycoconjugates expression in gastric mucosa, 6 lectins (Canavalia ensiformis agglutinin - Con A, Sambucus nigra agglutinin - SNA, wheat germ agglutinin - WGA, soybean agglutinin - SBA, Helix pomatia agglutinin - HPA, peanut agglutinin - PNA) were used. Carbohydrate determinants were visualized according to the lectin-peroxidase-diaminobenzidine staining protocol. Biopsy material was obtained and processed by conventional histological methods. The samples from 84 patients (54 with CNAG) with low (n = 34) and high grade (n = 20) dysplasia, 38 patients were H. pylori-infected and 26 patients - H. pylori-noninfected) were used. The comparison group included 30 persons with CNAG without dysplasia (16 patients H. pylori-infected and 14 - noninfected). RESULTS: In comparison to normal gastric mucosa, a low affinity of Con A was shown in 80% of patients with non-infected CNAG and 90% of H. pylori associated CNAG. In 70% of H. pylori-infected patients with CNAG and low grade dysplasia there was an increase of SNA expression compared with non-infected patients (p < 0.05). Regarding SBA labeling no differences were detected in the studied groups (p < 0.05). In H. pylori infected patients with CNAG and low grade dysplasia, WGA, HPA and PNA showed a strong reactivity with the gastric mucosa cells in 80; 75%, and 60% of patients, respectively. CONCLUSION: We suggest that a set of lectins in reaction with gastric epithelial and glandular cells can be used as a tool to obtain information about the dysplastic changes of the gastric mucosa and may offer new insight into gastric carcinogenesis and precancerous lesions treatment.

Helicobacter pylori resistance to clarithromycin in Reunion Island.

OBJECTIVE: The increasing resistance of Helicobacter pylori to clarithromycin led to developing new eradication treatment regimens. The objective of our observational study was to determine the proportion of H. pylori strains resistant to clarithromycin in infected patients in Reunion Island and to suggest a first-line treatment in agreement with the local ecology. PATIENTS AND METHODS: We included 200 patients who underwent esophagogastroduodenoscopy at the University Hospital of Saint-Pierre from February to July 2014. H. pylori was isolated from 73 patients. RESULTS: A wild-type susceptibility profile to clarithromycin was observed in 64 isolates (87.7%) and nine isolates (12.3%) had a resistant mutation profile. CONCLUSION: With a proportion of resistant strains below the critical threshold of 15%, physicians in Reunion Island may continue to prescribe the usual treatment regimen as a first-line option (clarithromycin, amoxicillin, and proton pump inhibitor for 14 days).

Association of Helicobacter pylori infection with dyspeptic symptoms in patients undergoing gastroduodenoscopy.

PURPOSE: To determine the prevalence of Helicobacter pylori in patients with non-ulcer dyspepsia and ulcer disease as well as in a control population undergoing endoscopic retrograde cholangiopancreatography (ERCP) for suspected pancreatic or biliary disease. PATIENTS AND METHODS: Forty-six eligible patients undergoing upper endoscopy at Massachusetts General Hospital were studied over a period of 18 months, as well as 24 patients undergoing ERCP for presumed pancreatic or biliary disease. Two biopsy specimens from the fundus and two from the antrum were taken for microbiologic and histopathologic analysis. Sera were examined by enzyme-linked immunoabsorbent assay. All specimens were processed in a blind fashion. Chi-square test with Yates' correction was used for statistical analysis. RESULTS: H. pylori was found in 31 of 46 (67%) study patients and in six of 24 (25%) control patients (by microbiologic or histologic techniques) (p less than 0.01). H. pylori was found in all patients with peptic ulcer disease and in 60% of patients without ulcers. No association between H. pylori and any specific gastrointestinal symptom was observed. H. pylori was identified in the fundus as often as in the antrum, although in the antrum the organism was more often associated with histologic gastritis. Compared with histology, serologic assays for IgG and IgA antibodies to H. pylori had sensitivities of 100% and 94%, and specificities of 86% and 76%, respectively. Reexamination of selected specimens without knowledge of their identity revealed that the specificity of serology exceeded 94% while the sensitivity of histologic and microbiologic studies may have been closer to 80%. CONCLUSIONS: H. pylori was more common in dyspeptic patients than in our control subjects undergoing ERCP. Multiple biopsy sites from fundus and antrum are required to exclude infection. Serologies of IgG and IgA were sensitive and specific for H. pylori, suggesting a possible role for non-endoscopic diagnosis of this infection. The frequent association of H. pylori with active inflammation rather than with quiescent gastritis is consistent with a pathologic role of this organism.

Rapid diagnosis of Campylobacter pylori by Gram's stain.

Campylobacter pylori (CP) is implicated as a probable pathogen in gastritis and peptic ulcer disease. A blinded prospective study of 112 subjects evaluated how Gram's-stained touch preparations of mucosal biopsies compared with culture, routinely processed hematoxylin and eosin (H and E) and Warthin-Starry (WS) staining in confirming the presence of CP. At endoscopic examination, two mucosal biopsies were taken from the gastric antrum and two from the fundus of each subject. One biopsy from each site was Gram's stained and cultured and the other submitted for H and E and WS. Fifty of the 112 subjects had positive results for CP by at least two of the tests (44.6%). Histologically, 48 (96%) of the CP-positive subjects showed the presence of gastritis. Of 55 subjects who had gastritis, 50 had CP (91%). If both sites in the stomach were taken into account, the sensitivity and specificity of Gram's staining in detecting CP were 92% and 100%, respectively. These results are comparable to H and E and WS and slightly better than culture. The diagnosis of CP can be made accurately, rapidly, and inexpensively by Gram's stained touch preparations of mucosal biopsies.

Histopathological study of porcine gastric mucosa with and without a spiral bacterium ("Gastrospirillum suis").

Tightly spiralled bacteria ("Gastrospirillum suis") were seen in the pyloric mucosa of the stomach of 13 (10.8%) of 120 pigs that appeared clinically healthy at slaughter and in the fundic mucosa of three (5.0%) out of 60 pigs. The spiral organism could not be cultured from any pig. Chronic gastritis was observed in the pyloric mucosa of 53 (44.2%) of 120 pigs and in the fundic mucosa of 7 (11.7%) of 60 pigs. The 13 pigs with spiral bacteria in the pyloric region comprised one animal (7.7%) with normal pyloric mucosa, two (15.4%) with "borderline gastritis", and 10 (76.9%) with chronic gastritis--in one instance accompanied by signs of activity (numerous polymorphonuclear cells). The three pigs with spiral bacteria in the fundic mucosa comprised two animals with a normal fundic region and one with "borderline gastritis". The presence of the spiral bacterium was significantly associated with pyloric gastritis (p = 0.013) and with numbers of lymphoid follicles (p = 0.014).

Helicobacter pylori and acid secretion: where are we now?

It is now widely recognized that H. pylori gastritis can produce marked alterations in gastric acid secretion. In subjects with an antral predominant gastritis there is increased release of gastrin and consequently increased acid secretion. Such subjects are at risk of developing duodenal ulcers. In other subjects the infection produces a marked body gastritis and this is associated with marked hyposecretion of acid or complete achlorhydria. These subjects have an increased risk of developing gastric cancer. Between these two ends of the disease spectrum lie the majority of H. pylori-infected subjects who have gastritis of both the antrum and body and no overall change in acid secretion. The reason why the infection exerts these divergent effects on gastric morphology and function remains unclear and is a challenge for ongoing research.

Helicobacter pylori isolated from stomach corpus and antrum: comparison of DNA patterns.

The genomic DNA of Helicobacter pylori was studied in strains isolated from two different sites of the stomach: the corpus and the antrum. 70 strains of H. pylori were found in 36 patients; 34 out of the 36 patients harboured the strain in both districts analysed. Restriction endonuclease analysis with Hae III and Hind III was used to compare the DNA patterns of strains isolated from the anatomical sites studied. Two pairs of DNA samples were not digested by these enzymes. 27 of the 32 pairs of the digested DNA appeared similar to each other. The analysis of chromosomal DNA in the remaining five pairs showed different electrophoretic patterns. These results indicate that the gastric mucosa can be colonized, at the same time, by strains of H. pylori with different genomic patterns, and this aspect can be important for epidemiological studies.