To evaluate the association between Helicobacter pylori (H. pylori) infection and gastric cancer (GC) according to tumor subtype in Korea.
H. pylori status was determined serologically using the enzyme-linked immunosorbent assay. In total, 2,819 patients with GC and 562 healthy controls were studied. A logistic regression method was used after adjusting for possible confounders.
The prevalence of H. pylori infection was significantly higher in the GC patients (84.7%) than in the controls (66.7%) (odds ratio [OR], 3.13; 95% confidence interval [CI], 2.46-3.97). The adjusted OR was significantly higher in H. pylori-infected patients aged <60 years (OR, 4.69; 95% CI, 3.44-6.38) than in those aged ≥60 years (OR, 1.48; 95% CI, 0.88-2.46; p<0.001). Subgroup analyses revealed no differences in seroprevalence between early gastric cancer (84.8%; OR, 3.01; 95% CI, 2.27-4.01) and advanced gastric cancer (84.6%; OR, 2.94; 95% CI, 2.24-3.85), cardia cancer (83.8%; OR, 2.98; 95% CI, 2.16-4.02) and noncardia cancer (84.8%; OR, 3.17; 95% CI, 2.48-4.04), and differentiated carcinoma (82.7%; OR, 2.99; 95% CI, 2.21-4.04) and undifferentiated carcinoma (86.8%; OR, 3.05; 95% CI, 2.32-4.00).
The seroprevalence of H. pylori was higher in GC patients than in healthy controls, especially in younger patients. H. pylori infection is associated with GC, regardless of the tumor location, stage, or differentiation.
Helicobacter pylori; Gastric cancer; Prevalence; Odds ratio; Subgroup analysis
Aims—To explore the correlation between the cagA status of Helicobacter pylori and the density and topographic localisation of H pylori.
Methods—Gastric antral biopsy specimens were taken from 716 consecutive patients, including 293 H pylori positive patients (124 men, 169 women; mean age, 52.6 years; range, 12–87). A serum sample was taken for determination of IgG anti-CagA antibodies (sensitivity of 94.4% and specificity of 92.5%). The density of H pylori was assessed semiquantitatively (grades I–IV) in biopsy specimens stained with the modified Giemsa stain. Topographic localisation was classified as follows: score A, H pylori closely attached to the mucosa; score B, H pylori attached to the mucosa and in the mucus; and score C, H pylori solely in the mucus.
Results—CagA antibodies were present in 154 (52.5%) of the patients. There was no significant difference in colonisation density and cagA status: grade I, 23 (14%); grade II, 78 (50.6%); grade III, 42 (27.5%); and grade IV, 11 (7.2%) in the cagA+ strains and 29 (21.2%), 57 (40.8%), 38 (27%), and 15 (11%), respectively, in the cagA- strains. There was no difference in topographic localisation between cagA+ and cagA-H pylori. Mean anti-CagA titres were 0.84, 0.84, 0.89, and 0.73 in patients with grades I–IV bacterial density, respectively.
Conclusion—Antibody titres do not correlate with H pylori density and there is no difference in density between cagA+ and cagA-H pylori strains. In addition there is no difference in topographic localisation between cagA+ and cagA- H pylori strains.
Key Words: Helicobacter pylori topography • Helicobacter pylori colonisation • density • antibody titres
BACKGROUND: Interleukin-10 (IL-10) is an 18 kDa peptide with a range of anti-inflammatory and immunosuppressive properties. AIM: To determine whether this cytokine is involved in gastric mucosal inflammation in Helicobacter pylori infection. METHODS: The production of IL-10 by antral mucosal biopsy specimens during short term in vitro culture was determined by measuring IL-10 content of supernatants by enzyme linked immunosorbent assay (ELISA). H pylori status was determined by serology and histology, with gastritis scored using the Sydney system. Tumour necrosis factor-alpha (TNF-alpha) content of supernatants was also determined in a subgroup of patients. RESULTS: IL-10 secretion was significantly greater in patients with H pylori associated chronic gastritis than in patients who were H pylori negative with normal mucosa/reactive changes, and those with H pylori negative chronic gastritis (p < 0.01 and < 0.05 respectively). There was a significant correlation overall between IL-10 secretion and chronic inflammation score (r = 0.40). Secretion of TNF-alpha, which was significantly higher in H pylori infected patients than uninfected patients with a normal mucosa (p < 0.04), correlated with scores for chronic inflammation and activity (r = 0.39 and 0.38 respectively), but was only weakly correlated with IL-10 secretion (r = 0.22, NS). CONCLUSIONS: Gastric mucosal production of IL-10 and TNF-alpha are increased in chronic gastritis associated with H pylori infection, and mucosal cytokine secretion varies with important histopathological aspects of gastric inflammation. Whereas the secretion of IL-10 in H pylori infection may be protective, limiting tissue damage caused by inflammation, it may also contribute towards failure of the immune response to eliminate the organism.
Previous studies suggested that polymorphisms of proinflammatory cytokine genes are important host genetic factors in Helicobacter pylori infection. The present study evaluated whether IL-8-251 polymorphism affected H. pylori eradication rate and to investigate the effect of H. pylori eradication on angiogenesis and the inflammatory process according to the IL-8-251 polymorphism. A total of 250 H. pylori-positive patients treated by endoscopic resection of the gastric neoplasm were classified into 3 groups (134 H. pylori-eradicated group, 19 H. pylori-eradication failure group, and 97 H. pylori-infected group). H. pylori status, histology, and angiogenic factor levels were evaluated at baseline, 6 months, and 18 months. H. pylori eradication rate was 92.9% in AA genotype, 85.7% in AT genotype and 88.4% in TT genotype (P value = 0.731). Elevated IL-8 and matrix metalloproteinase-9 concentrations in H. pylori-infected gastric mucosa were reversible by successful eradication of H. pylori, independent of the IL-8-251 polymorphism. It is suggested that elevated IL-8 and MMP-9 concentrations in H. pylori-infected gastric mucosa are altered significantly after successful eradication and these conditions continue for 18 months. However, IL-8-251 polymorphism does not affect H. pylori eradication rate and the sequential changes of related angiogenic factors after H. pylori eradication in Koreans.
Helicobacter pylori; Interleukin-8; Polymorphism
Serological testing for Helicobacter pylori infection is one of the diagnostic methods of choice. Various commercial kits that use different antigens have been developed, but data on their diagnostic accuracy and direct comparisons between the tests are lacking. We aimed to evaluate the sensitivity, specificity, and predictive value of three immunoglobulin G enzyme-linked immunosorbent assay kits: Pylori stat, Helico-G, and Premier H. pylori. Serum samples and gastric biopsy findings from 76 patients were evaluated. We found by using a priori cutoff values that the Pylori stat, Helico-G, and Premier kits had overall sensitivities of 96, 96, and 88%, respectively, and specificities of 94, 86, and 96%, respectively, compared with gastric biopsy findings. For 232 serum samples, the Pylori stat test and a previously validated standard serological assay on which the test was based disagreed in 3% of the cases, while for 76 samples that were tested, Helico-G and a previously validated standard assay on which it was based disagreed in 8% of the cases. The intra- and interassay precision of each of the test kits was high. We conclude that serology based on any of these commercial tests represents a reliable and valid method for the diagnosis of H. pylori whether or not highly purified antigens are used.
Aim: This study was carried out to assess the prevalence of Helicobacter pylori infection
in various ABO blood groups of people of Kashmir.
Method: The study comprised 80 individuals – 50 peptic ulcer patients (whose disease
was diagnosed by endoscopy) and 30 asymptomatic volunteers. Every subject's
blood group and Rhesus status was determined by standard serological tests. Helicobacter
pylori infection was diagnosed by three different methods viz., one minute endoscopy
room test (urease test), Gram staining and by histology. The detection of Helicobacter
pylori by histological examination using Giemsa staining was taken as the ‘gold standard’
for the presence of Helicobacter pylori infection.
Results: Out of 80 individuals, 67 were males and 13 females aged between 18–65
years. The majority of peptic ulcer patients had blood group ‘O’ (n = 28.56%). The
prevalence of Helicobacter pylori infection amongst peptic ulcer patients was 76%.
There was no difference in Helicobacter pylori positivity in various blood groups.
Conclusion: Blood group ‘O’ though a risk factor for peptic ulcer (Duodenal ulcer)
is not a risk factor for acquiring Helicobacter pylori infection.
AIM: To investigate screening makers for gastric cancer, we assessed the association between gastric cancer and serum pepsinogens (PGs).
METHODS: The subjects comprised 450 patients with gastric cancer, 111 individuals with gastric atrophy, and 961 healthy controls. Serum anti-Helicobacter pylori (H. pylori) immunoglobulin G (IgG), PGIand PG II were detected by enzyme-linked immunosorbent assay. Gastric atrophy and gastric cancer were diagnosed by endoscopy and histopathological examinations. Odds ratios and 95%CIs were calculated using multivariate logistic regression.
RESULTS: Rates of H. pylori infection remained high in Northeastern China. Rates of H. pylori IgG positivity were greater in the gastric cancer and gastric atrophy groups compared to the control group (69.1% and 75.7% vs 49.7%, P < 0.001). Higher levels of PG II (15.9 μg/L and 13.9 μg/L vs 11.5 μg/L, P < 0.001) and lower PGI/PG II ratio (5.4 and 4.6 vs 8.4, P < 0.001) were found in patients with gastric cancer or gastric atrophy compared to healthy controls, whereas no correlation was found between the plasma PGIconcentration and risk of gastric cancer (P = 0.537). In addition, multivariate logistic analysis indicated that H. pylori infection and atrophic gastritis were independent risk factors for gastric cancer. Lower plasma PGI/PG II ratio was associated with higher risks of atrophy and gastric cancer. Furthermore, plasma PG II level significantly correlated with H. pylori-infected gastric cancer.
CONCLUSION: Serum PG II concentration and PGI/PG II ratio are potential biomarkers for H. pylori-infected gastric disease. PG II is independently associated with risk of gastric cancer.
Gastric cancer; Pepsinogens; Helicobacter pylori; Gastric atrophy; Screening
BACKGROUND: Approximately 10% of patients presenting with dyspepsia to the general practitioner have peptic ulcers; the large majority of which are related to infection with Helicobactor pylori. Office-based tests for H. pylori detection are generally validated and evaluated in selected patient groups. AIM: To evaluate the clinical effectiveness of a whole-blood serology test for infection with Helicobacter pylori in detecting peptic ulcer disease (PUD) in daily general practice. METHOD: A descriptive study of 171 primary care dyspepsia patients selected for open-access endoscopy in primary care and aged between 18 and 75 years, in 92 general practices in central, southern, and eastern parts of the Netherlands. H. pylori status was assessed using the BM-test Helicobacter pylori, which is identical to the Helisal test. Dyspepsia severity score was measured using a validated symptom score. Symptom characteristics and probability of relevant disease were assessed by the general practitioner. Endoscopy was carried out in local hospitals. Diagnostic outcome of both endoscopy and H. pylori reference test was supplied by local specialists. The BM-test was evaluated against endoscopic results. RESULTS: A high number (61.8%) of false-negative BM-tests resulted in a low sensitivity (95% confidence interval [CI] = 48-75%) for detection of H. pylori infection. Only 12 out of 32 patients with PUD had a positive BM-test, resulting in a positive likelihood ratio (LR) for PUD of 1.41 and a negative LR of 0.85. CONCLUSIONS: This study confirms the relatively poor performance of the BM-test in daily general practice, and shows the limited diagnostic value of H. pylori office-tests for detecting PUD in primary care. The discriminative value of the test result is too small to support either a 'test-and-endoscope' of a 'test-and-treat' strategy in general practice.
AIMS--To investigate the association between histologically confirmed gastritis, carriage of Helicobacter pylori and pepsinogen (PG) I and PG II concentrations. METHODS--Prospective study of 81 dyspeptic patients undergoing upper gastrointestinal endoscopy was made. The extent of gastric mucosal inflammation and the presence of H pylori was determined, and serology to evaluate PG I and II concentrations and IgG titres to H pylori was carried out. RESULTS--The presence of H pylori was strongly correlated with high IgG antibody titres to H pylori and gastritis. Patients who were H pylori positive had significantly higher PG I and PG II concentrations and a significantly lower PG I:PG II ratio than patients who were negative for H pylori. In 13 patients with duodenal ulcer and H pylori positive gastritis serum PG I concentrations were significantly higher than in H pylori positive patients without duodenal ulcer. Significant correlations were found between the age of patients and serum PG II, the PG I:PG II ratio, IgG antibodies to H pylori, the severity of body gastritis and H pylori infection, and between the degree of gastritis in the body of the stomach and the PG II concentration. CONCLUSIONS--Serum PG I and II concentrations, together with a fall in the PG I:PG II ratio, could be used as predictors of H pylori infection as well as serum IgG antibody response to H pylori.
Infection with Helicobacter pylori is an important risk factor for gastric cancer in humans. We compared the clinicopathologic features of gastric cancer patients based on H. pylori infection.
Materials and Methods
We prospectively studied 155 patients who had gastric cancer and underwent gastrectomies in 1 hospital in Korea. We examined H. pylori infections using the rapid urease test (RUT) with gastrectomy specimens and collected clinical and pathologic data.
The number of H. pylori infections based on the RUT was 137 (88%). The H. pylori-negative group was significantly associated with AGC and tumor histology. H. pylori infection was significantly correlated with type I/IIa in EGC and type III/IV/V in AGC. AGC was significantly correlated with larger tumor size, lymphatic invasion, perineural invasion, and H. pylori infection based on univariate and multivariate analyses.
We report the prevalence of H. pylori based on the RUT in gastric cancer patients. H. pylori infection influences the tumor histology, progression, and growth type of gastric cancer.
Helicobacter pylori; Stomach neoplasms; Phenotype
AIM: To explore the role of Helicobacter pylori (H pylori) infection on the risk of digestive tract cancers.
METHODS: In total, 199 oral squamous-cell carcinoma (SCC), 317 esophageal SCC, 196 gastric cardia and non-cardia adenocarcinoma and 240 colon adenocarcinoma patients were recruited for serum tests of H pylori infection. Two hospital- and one community-based control groups were used for the comparisons. H pylori seropositivity was determined by an enzyme linked immunosorbent assay method against H pylori IgG.
RESULTS: Presence of H pylori infection was significantly inversely associated with esophageal SCC [adjusted odds ratio (AOR): 0.315-0.472, all P-value < 0.05] but positively associated with gastric adenocarcinoma (both cardia and non-cardia) (AOR: 1.636-3.060, all P-value < 0.05) in comparison to the three control groups. Similar results were not found in cancers of the oral cavity and colon.
CONCLUSION: Our findings support the finding that H pylori seropositivity is inversely associated with esophageal SCC risk, but increases the risk of gastric cardia adenocarcinoma.
Helicobacter pylori infection; Oral cancer; Esophageal squamous cell carcinoma; Gastric cardia adenocarcinoma; Colon cancer
Background—An endoscopic procedure that uses a pH
indicator called phenol red to assess Helicobacter pylori
infected gastric mucosa has recently been developed. This test makes it
possible to take biopsy specimens from H pylori infected areas.
Aim—This test was applied to patients with early
gastric cancers to clarify the role of H pylori in gastric carcinogenesis.
Subjects—Sixty five patients with early gastric
cancer (50 with differentiated adenocarcinoma and 15 with
Methods—Patients with early gastric cancer
underwent the endoscopic phenol red test before their operation. In
this test, areas infected with H pylori can be observed as
"coloured" areas where phenol red was turned from yellow to red.
Results—H pylori infection was
significantly (p<0.001) more frequent in patients with differentiated
adenocarcinomas than in those with undifferentiated adenocarcinomas.
Differentiated adenocarcinomas were usually located in areas of mucosa
infected with H pylori, but undifferentiated
adenocarcinomas were frequently located in non-infected areas.
Conclusion—H pylori may be a strong
risk factor for differentiated early gastric cancer.
endoscopic phenol red test; Helicobacter
pylori; gastric cancer; differentiated adenocarcinoma; high risk
The identification of Helicobacter pylori-strain specific factors that correlate with clinical outcome has remained elusive. We investigated possible relationships between a group of H. pylori antigens and clinical outcome and compared an immunoblot assay kit (HelicoBlot, version 2.1 [HB 2.1]; Genelabs Diagnostics) with an established serological test, the high-molecular-weight cell-associated protein test (HM-CAP). We used sera from 156 Thai patients with different disease presentations, including 43 patients with gastric cancer, 64 patients with gastric ulcer, and 49 patients with nonulcer dyspepsia (NUD). HB 2.1 was compared to HM-CAP as a diagnostic test for H. pylori infection. The seroprevalence of H. pylori was significantly higher among gastric cancer patients than among patients with NUD (93 and 67%, respectively; P < 0.01). Among the H. pylori-seropositive patients, the presence of the antibody to the 37,000-molecular-weight antigen (37K antigen) was inversely related to the presence of gastric cancer (e.g., for gastric cancer patients compared with NUD patients, odds ratio [OR] = 0.28 and 95% confidence interval [CI] = 0.1 to 0.8). The presence of antibody to the 35K antigen was higher in gastric ulcer patients than in NUD patients (OR = 11.5; 95% CI = 2.4 to 54.3). The disease associations of antibodies to the 35K and 37K antigens are consistent with the possibility that these antigens are either indirect markers for H. pylori-related diseases or have specific active or protective roles in H. pylori-related diseases.
In 82 patients who underwent gastroduodenoscopy, acute and chronic gastric mucosal inflammation was scored for severity, and systemic humoral immune responses to Helicobacter pylori antigens were assessed by enzyme-linked immunosorbent assays. On the basis of culture, gastric histology, and serologic evaluation, 33 patients were classified as H. pylori infected and 36 were classified as uninfected. Thirteen patients had negative cultures and stains but were seropositive and were analyzed separately from the other two groups. Specific serum immunoglobulin G (IgG) subclass responses to H. pylori whole-cell antigens and specific IgG responses to the 54-kDa heat shock protein homolog (Hp54K) and vacuolating cytotoxin were significantly greater in infected than in uninfected patients as were specific IgA responses to whole-cell antigens and cytotoxin (P < 0.001). Among the H. pylori-infected persons, serum IgG responses to Hp54K and to the vacuolating cytotoxin were correlated with acute mucosal inflammatory scores. In contrast, serum IgA responses to whole-cell sonicate and to vacuolating cytotoxin were inversely related to chronic inflammatory scores. By multivariant regression analysis, only specific serum IgG responses to Hp54K correlated with severity of inflammation (both acute and chronic; P < 0.001); these responses may be markers of inflammation or these antibodies could play a direct role in the pathogenesis of H. pylori-induced inflammation.
eradication therapy is routinely used for treating patients with peptic
Aims—To assess the value of symptomatic response
to H pylori eradication therapy as a marker of
post-treatment H pylori status.
Patients and methods—One hundred and nine
dyspeptic patients with active duodenal or gastric ulceration
associated with H pylori infection had their symptoms
measured by a validated questionnaire before and three months following
H pylori eradication therapy. The symptomatic response was
compared with post-treatment H pylori status as determined
by the 14C urea breath test.
Results—An eradication rate of 84% was achieved.
Of the 92 patients eradicated of H pylori, 47%
experienced complete or near complete resolution of dyspepsia. Of the
17 patients in whom the infection was not eradicated, only one (6%)
experienced resolution of dyspepsia. Resolution of dyspepsia was
therefore a powerful predictor of eradication of H pylori
with a predictive value of 98%. In contrast, persistence of dyspepsia
was a weak predictor of persisting infection with a predictive value of
only 25%. Excluding patients with endoscopic evidence of coexisting
oesophagitis and/or retrosternal discomfort or reflux at initial
presentation did not increase the predictive value of persisting
dyspepsia for persisting infection.
Conclusions—Complete resolution of dyspeptic
symptoms is a powerful predictor of eradication of H
pylori infection in ulcer patients. Persistence of symptoms is a
weak predictor of persisting infection and patients with persisting
dyspepsia must have their H pylori status rechecked to
guide future management.
Helicobacter pylori; dyspepsia; ulcer
disease; eradication therapy; reflux disease
Helicobacter pylori is implicated in various gastroduodenal diseases and many tests are available for its detection. The present study attempted to document the morphological changes in the gastric mucosa induced by H. pylori colonization and correlate them with the severity of the infection. The study also compared various diagnostic tests and evaluated the different staining methods used for H. pylori detection, especially immunohistochemical identification.
Patients and Methods:
One hundred and two patients with dyspepsia were included. Enzyme-linked immunosorbent assay (ELISA) for H. pylori-specific immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M (IgM) was used. Rapid urease test was performed on endoscopic biopsy and it was stained with hematoxylin and eosin (H and E), modified Giemsa, and immunohistochemical stains.
A significant correlation was found between the density of H. pylori and severity of gastritis. A significant correlation was observed between serology (especially when used in combination, IgG and IgA) and status of H. pylori. Immunohistochemical staining enhanced the diagnostic yield of H. pylori detection.
Immunohistochemistry (IHC) should be used judiciously, whereas simple and economical tests like modified Giemsa should be used routinely for the detection of H. pylori. Combined ELISA (IgG and IgA) should be preferred over single ELISA. Simultaneous morphological and serological detection of H. pylori is preferable as H. pylori may not be detected on morphology alone due to its patchy distribution in the stomach.
Helicobacter pylori; immunohistochemistry; serology
Aim—To determine whether two recently described staining methods (the modified McMullen's and the Helicobacter pylori silver stain HpSS methods) used for the histological identification of H pylori organisms are superior to two established techniques (the modified Giemsa and anti-H pylori antibody immunostain) in terms of availability, reproducibility, rapidity, sensitivity, and cost.
Methods—Histological sections from 63 paired gastric biopsies from adult patients previously investigated for dyspepsia were stained with the four methods and these were assessed blindly and independently by two observers. Of the 63 patients, 30 were originally negative in all tests for H pylori infection, 30 were positive, and the remaining three cases had discordant results using a combination of five tests (rapid biopsy urease test, urea breath test, culture, serology, and histology).
Results—Interobserver agreement was best with the antibody method (98%), followed by the McMullen's (90%), Giemsa (87%), and HpSS (85%). Of the 60 "gold standard" positive and negative cases, 30 were positive by the modified Giemsa stain, 29 by the McMullen's method, 29 by HpSS, and 30 by the antibody stain. However, there were two false positives with the HpSS method. The modified Giemsa is the cheapest and easiest to perform technically.
Conclusions—When H pylori are present, careful examination will almost always reveal them, whichever of these stains is used. However, the modified Giemsa stain is the method of choice because it is sensitive, cheap, easy to perform, and reproducible.
Key Words: Helicobacter organisms • histological identification • staining methods
Increased epithelial cell proliferation is associated with an increased risk of adenocarcinoma and is associated with Helicobacter pylori infection. The aim of this study was to assess both gastric epithelial cell proliferation and the influence of H pylori infection on cell kinetics in the progression from normal mucosa to gastric carcinoma. One hundred and forty four subjects were assigned to study groups based on diagnosis and H pylori status: microscopically normal mucosa and H pylori negative (n = 28); chronic active gastritis and H pylori positive (n = 83); atrophic gastritis (n = 9); intestinal metaplasia (n = 19); gastric carcinoma (n = 12). Gastric antral epithelial cell proliferation was assessed using the in vitro bromodeoxyuridine immunohistochemical technique and expressed as the labelling index per cent (LI%). Subjects with chronic atrophic gastritis, intestinal metaplasia or gastric cancer have increased gastric epithelial cell proliferation compared with normal mucosa (LI% mean (SEM): 5.14 (0.6), 4.68 (0.3), 6.50 (0.5) v 3.08 (0.2), p < 0.001). This increase in gastric epithelial cell proliferation was not influenced by H pylori status. Gastritis associated with H pylori had an increased LI% compared with normal controls or subjects with H pylori negative gastritis (4.98 (0.2) v 3.08 (0.2), 3.83 (0.2), p < 0.01). H pylori infection although associated with an increased epithelial cell proliferation in subjects with chronic gastritis, does not influence the increased epithelial cell proliferation seen in subjects with precancerous lesions or gastric carcinoma. This is further evidence that H pylori may be an initiating step in gastric carcinogenesis.
In 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.
347 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.
H. 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.
In 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.
AIM: To investigate the changing pattern of different histological parameters occurring in the stomach tissue of Helicobacter pylori (H pylori) infected tribal populations and duodenal ulcer patients among ethnic Bengalis and correlation of the genotypes of H pylori with different histological parameters.
METHODS: One hundred and twelve adult individuals were enrolled into this study between 2002 and 2004. Among them, 72 had clinical features of duodenal ulcer (DU) from ethnic Bengali population and 40 were asymptomatic ethnic tribals. Endoscopic gastric biopsy samples were processed for histology, genotyping and rapid urease test. Histologically, haematoxylin and eosin staining was applied to assess the pathomorphological changes and a modified Giemsa staining was used for better detection of H pylori. For intestinal metaplasia, special stainings, i.e. Alcian blue periodic acid-Schiff and high iron diamine-Alcian blue staining, were performed. PCR was performed on bacterial DNA to characterize the presence or absence of virulence-associated genes, like cagA, and distribution of different alleles of vacA and iceA.
RESULTS: Intraglandular neutrophil infiltration, a hallmark of activity of gastritis, was present in 34 (94%) of tribals (TRs) and 42 (84%) of DU individuals infected with H pylori. Lymphoid follicles and aggregates, which are important landmarks in H pylori infection, were positive amongst 15 (41%) of TRs and 20 (40%) of DU subjects. Atrophic changes were observed in 60% and 27.7%, respectively, among DU cases and tribals (P > 0.003). Metaplastic changes were detected in low numbers in both groups. Moderate to severe density distribution of H pylori in the gastric mucosa was 63% among TRs, whereas it was 62% in DU subjects. There were no significant differences in the distribution of virulence-associated genes like cagA, vacA and iceA of H pylori strains carried by these two populations.
CONCLUSION: Our study showed almost similar distribution of inflammatory cells among asymptomatic tribals and DU Bengali patients. Interestingly, the tribal population are free from any clinical symptoms despite evidence of active histologic gastritis and infection with H pylori strains carrying similar virulence markers as of strains isolated from patients with DU. There was an increased cellular response, especially in terms of neutrophil infiltration, but much lower risk of developing atrophy and metaplastic changes among the tribal population.
Helicobacter pylori; Tribal; Neutrophil; Mononuclear cells infiltration; Lymphoid follicles
Hypoxia-inducible factor-1 (HIF-1)α expression was studied in the gastric carcinogenesis sequence and as a prognostic factor in surgically resected gastric and gastro-oesophageal junction tumours. Protein expression was examined using immunohistochemistry on formalin-fixed biopsies of normal mucosa (n=20), Helicobacter pylori associated gastritis (n=24), intestinal metaplasia (n=24), dysplasia (n=12) and intestinal (n=19) and diffuse (n=21) adenocarcinoma. The relationship between HIF-1α expression and prognosis was assessed in resection specimens from 177 patients with gastric and gastro-oesophageal junction adenocarcinoma. Hypoxia-inducible factor-1α expression was not observed in normal gastric mucosa but increased in density (P<0.01) and intensity (P<0.01) with progression from H. pylori-associated gastritis, intestinal metaplasia, dysplasia to adenocarcinoma. The pattern of staining in the resection specimens was focally positive in 49 (28%) and at the invasive tumour edge in 41 (23%). Invasive edge expression was associated with lymph node metastases (P=0.034), advanced TNM stage (P=0.001) and was an adverse prognostic factor for cancer-specific survival (P=0.019). In univariate analysis and in comparison with tumours not expressing HIF-1α, invasive edge staining was associated with a hazard ratio of 1.6 (95% CI 1.0−2.5) and focally positive staining a hazard ratio of 0.7 (95% CI 0.5−1.2). Hypoxia-inducible factor-1α lost prognostic significance in multivariate analysis. The results suggest HIF-1α is involved in gastric carcinogenesis and disease progression, but is only a weak prognostic factor for survival.
gastric cancer; gastro-oesophageal junction tumours; HIF-1α
The cadherin–catenin complex is the key component of the adherens junction in epithelial cells, and changes in this complex are implicated in gastric adenocarcinoma. Germline mutations in E‐cadherin have been described in diffuse‐type gastric adenocarcinoma. Helicobacter pylori infection is the first stage in gastric carcinogenesis.
To determine whether H pylori was associated with changes in the complex, and whether this was affected by virulence of the strain.
Epithelial cell lines were cultured with H pylori using the wild‐type pathogenic and non‐pathogenic strains and CagE null and VacA null isogenic mutants. Gastric biopsy specimens at endoscopy were obtained from patients with (n = 17) and without (n = 15) H pylori infection, and E‐cadherin and β–catenin expression was assessed by immunohistochemistry. H pylori was typed by polymerase chain reaction from these patients for CagE and VacA.
In vitro studies showed that coculture with a pathogenic strain of H pylori led to disruption of epithelial junctional β‐catenin expression, but without evidence of nuclear translocation or signalling. This effect was independent of a functional Cag pathogenicity island and vacuolating activity, but dependent on live bacteria. No marked differences in β‐catenin or E‐cadherin expression were seen in gastric biopsy specimens in patients with and without H pylori infection.
Acute H pylori infection disrupts junctional β‐catenin in vitro, but chronic infection by H pylori has no effect on E‐cadherin and β‐catenin expression, as seen in gastric biopsy specimens at the initial gastritis stage of the proposed Correa pathway of gastric carcinogenesis. A later effect at the later stages of atrophy or intestinal metaplasia cannot be ruled out.
Helicobacter pylori is a major etiological agent in gastroduodenal disorders. The adhesion of H. pylori to human gastric epithelial cells is the initial step of H. pylori infection. Inhibition of H. pylori adhesion is thus a therapeutic target in the prevention of H. pylori infection. Experiments were performed to evaluate the effect of rebamipide, a novel antiulcer agent, on H. pylori adhesion to gastric epithelial cells. MKN-28 and MKN-45 cells, derived from human gastric carcinomas, were used as target cells. Ten H. pylori strains isolated from patients with chronic gastritis and gastric ulcer were used in the study. We evaluated the effect of rebamipide on H. pylori adhesion to MKN-28 and MKN-45 cells quantitatively using our previously established enzyme-linked immunosorbent assay. The adhesion of H. pylori to MKN-28 and MKN-45 cells was significantly inhibited by pretreatment of these cells with 100 μg of rebamipide per ml. However, the adhesion was not affected by the pretreatment of H. pylori with rebamipide. On the other hand, the viabilities of H. pylori, MKN-28 cells, and MKN-45 cells were not affected by rebamipide. Our studies suggest that rebamipide inhibits the adhesion of H. pylori to gastric epithelial cells.
Helicobacter pylori infection is common in Jamaica. Describing its epidemiology in a population-based study depends largely on serology, but serologic assays have not been validated in this population. To address this issue, we examined the presence of H. pylori infection in 30 sequential adult patients with gastroduodenal symptoms by three biopsy-based methods (rapid urease test, histology, and culture) as well as by one research and two commercial enzyme-linked immunosorbent assays (ELISAs). A patient was considered H. pylori positive if the organism was detected by at least one biopsy-based method. Eighteen (60%) of the 30 patients were H. pylori positive by these criteria, whereas 21 (70%) were seropositive for H. pylori immunoglobulin G by our research ELISA. The presence of H. pylori infection in patients with gastric cancer and those with chronic gastritis was missed by biopsy-based methods but was detected by serologic assays. This observation indicates that serologic assays may be better suited for the detection of this infection in a population in which H. pylori-associated pathology is prevalent. The performance of our research ELISA in detecting biopsy-based H. pylori-positive cases was excellent, with a sensitivity and specificity of 100% and 75%, respectively. Molecular genotyping of the isolates revealed that the predominant H. pylori genotypes in this cohort of Jamaicans were cagA+ vacA slb-m1, and iceA2. The validated serologic assay enables us to interpret epidemiologic data from population-based studies in Jamaica by comparison to those from other populations.
AIM: Helicobacter pylori is associated with gastric cancer. Our aim was to investigate whether CagA or VacA seropositivity provides additional risk for gastric cancer. METHODS: Sera from 110 gastric cancer patients were sex and aged matched with asymptomatic controls. H pylori status was determined by IgG enzyme immunoassay (HM-CAP EIA); CagA status was assessed by enzyme linked immunosorbent assay (ELISA) (OraVax) and immunoblotting (Chiron), and VacA status by immunoblotting using recombinant proteins as antigens. RESULTS: H pylori infection was associated with an increased risk of gastric cancer (odds ratio (OR) = 2.19, 95% confidence interval 1.17 to 4.1). Subgroup analysis showed a significant association with intestinal type (OR = 2.94, 1.35 to 6.41), distal type (OR = 2.97, 1.39 to 6.33), early gastric cancer (OR = 3.74, 1.54 to 9.06), and age < or = 55 years (OR = 8.33, 2.04 to 34.08), but not with diffuse type (OR = 0.83), proximal type (OR = 1.0), advanced gastric cancer (OR = 1.13), or age > 55 years (OR = 1.40). Serum CagA IgG and VacA antibody positivity was present in similar proportions in patients with and without cancer, with no significant differences in histological classification, clinical stage, or location (p > 0.3). CONCLUSIONS: H pylori infection causes chronic gastritis and is associated with the development of gastric cancer. Neither CagA nor VacA seropositivity added additional information or stratification.