Potential association of eEF1A dimethylation at lysine 55 in the basal area of Helicobacter pylori-eradicated gastric mucosa with the risk of gastric cancer: a retrospective observational study.

BACKGROUND: Although eradication therapy for chronic Helicobacter pylori (H. pylori) reduces the risk of gastric cancer (GC), its effectiveness is not complete. Therefore, it is also critically important to identifying those patients who remain at high risk after H. pylori eradication therapy. Accumulation of protein methylation is strongly implicated in cancer, and recent study showed that dimethylation of eEF1A lysine 55 (eEF1AK55me2) promotes carcinogenesis in vivo. We aimed to investigate the relationship between eEF1A dimethylation and H. pylori status, efficacy of eradication therapy, and GC risk in H. pylori-eradicated mucosa, and to reveal the potential downstream molecules of eEF1A dimethylation. METHODS: Records of 115 patients (11 H. pylori-negative, 29 H. pylori-positive, 75 post-eradication patients) who underwent upper gastrointestinal endoscopy were retrospectively reviewed. The eEF1A dimethyl level was evaluated in each functional cell type of gastric mucosa by immunofluorescent staining. We also investigated the relationship between eEF1AK55me2 downregulation by CRISPR/Cas9 mediated deletion of Mettl13, which is known as a dimethyltransferase of eEF1AK55me2. RESULTS: The level of eEF1A dimethylation significantly increased in the surface and basal areas of H. pylori-positive mucosa compared with the negative mucosa (surface, p = 0.0031; basal, p = 0.0036, respectively). The eEF1A dimethyl-levels in the surface area were significantly reduced by eradication therapy (p = 0.005), but those in the basal area were maintained even after eradication therapy. Multivariate analysis revealed that high dimethylation of eEF1A in the basal area of the mucosa was the independent factor related to GC incidence (odds ratio = 3.6611, 95% confidence interval = 1.0350-12.949, p = 0.0441). We also showed the relationship between eEF1A dimethylation and expressions of reprogramming factors, Oct4 and Nanog, by immunohistochemistry and in vitro genome editing experiments. CONCLUSIONS: The results indicated that H. pylori infection induced eEF1A dimethylation in gastric mucosa. The accumulation of dimethyl-eEF1A in the basal area of the mucosa might contribute to GC risk via regulation of reprograming factors in H. pylori eradicated-gastric mucosa.

Analysis of long-term serological and histological changes after eradication of Helicobacter pylori.

Stratification of gastric cancer risk by measuring serological biomarkers is useful for screening of gastric cancer. However, this method has problem such as overlooking past infected patients. We aimed to evaluate the association between Helicobacter pylori infection status and serological biomarkers. We divided 5,268 patients according to Helicobacter pylori infection status and past infected patients were divided into 12 groups according to time elapsed since eradication. We analyzed mean serum H. pylori immunoglobulin G antibody, pepsinogen titers, histological and endoscopic atrophy score of each group. Mean H. pylori immunoglobulin G antibody showed a decreasing tendency, there was no significant difference from the uninfected group at 11 years after eradication (p = 0.19). PGI, PGII decreased in short term after eradication. However, both PGI and PGII gradually increased as long-term changes after eradication, became comparable to those in the uninfected group (p = 0.41, p = 0.37, respectively). Histological atrophy improved gradually, became equivalent to uninfected group. Endoscopic atrophy score did not improve for long term after eradication. In conclusion, patients with long term after eradication reach the uninfected condition serologically, histologically. Endoscopic assessment of gastric mucosal atrophy may be useful for accurate assessment of gastric cancer risk.

Immunohistochemical differences in gastric mucosal damage between nodular and non-nodular gastritis caused by Helicobacter pylori infection.

In this study, the level of cell damage were analyzed immuno-histochemically to clarify the association between nodular gastritis and undifferentiated gastric cancer. Thirty patients of nodular gastritis were enrolled as the nodular gastritis group. Thirty patients of non-nodular gastritis were enrolled as the control group. They were evaluated according to the updated Sydney system and used for immunohistochemical staining (p53, Ki-67, E-cadherin, and 8-OHdG). The scores based on the updated Sydney system were significantly higher in the nodular group than in the non-nodular group for histologically assessed inflammation and activity in the gastric corpus (1.91 ±â€„0.77 vs 1.58 ±â€„0.60, p = 0.049, 0.83 ±â€„0.81 vs 0.44 ±â€„0.64, p = 0.032). On immunostaining, the detection of E-cadherin was lower in the nodular group for both the antrum (1.0 ±â€„0.62 vs 1.47 ±â€„0.85, p = 0.047) and the corpus (1.16 ±â€„0.81 vs 1.48 ±â€„0.71, p = 0.043) and the p53 labeling index of the gastric corpus was higher in the nodular group than in the non-nodular group (3.06 ±â€„1.94 vs 2.03 ±â€„1.99, p = 0.015). Nodular gastritis showed significant severe inflammation and immunohistochemical cell damage compared with non-nodular gastritis. These findings may play an important role in the oncogenesis of undifferentiated gastric cancer in nodular gastritis.

Gastric mucosal changes, and sex differences therein, after Helicobacter pylori eradication: A long-term prospective follow-up study.

BACKGROUND AND AIM: Improvement of atrophic gastritis and intestinal metaplasia (IM) is considered to reduce the gastric cancer risk, but whether it can be achieved by H. pylori eradication (HPE) remains controversial. To evaluate the effect of HPE, we observed the gastric mucosa for up to17 years after HPE and sex differences in gastric mucosa. METHODS: In total, 172 patients (94 males, 78 females) with HPE were enrolled. Annual histological evaluations were performed for up to 17 years. The grades of mononuclear cells, neutrophils, atrophy, IM in the antrum and corpus were evaluated using the updated Sydney system. RESULTS: Relative to the pre-HPE period, atrophy had improved significantly 1 year after HPE in the antrum (1.50 ± 0.75 vs. 1.21 ± 1.25, P < 0.01) and corpus (0.59 ± 0.75 vs. 0.18 ± 0.52, P < 0.05). IM showed no significant change during 17 years after HPE at either biopsy site. Atrophy scores did not differ significantly between males and females. IM scores were significantly higher in males than in females before eradication (antrum, 0.67 ± 0.94 vs. 0.44 ± 0.77, P = 0.003, corpus, 0.20 ± 0.62 vs. 0.047 ± 0.21, P = 0.0027) and at most observation timepoints. CONCLUSIONS: During 17 years after HPE, atrophy, but not IM, improved significantly at the greater curvatures of the antrum and corpus. IM was significantly more severe in males than in females. Careful follow-up after HPE based on sex differences in gastric mucosal characteristics is important.

Helicobacter pylori infection modulates endogenous hydrogen sulfide production in gastric cancer AGS cells.

BACKGROUND: Persistent Helicobacter pylori infection induces gastric mucosal atrophy, which is a precancerous condition. Hydrogen sulfide (H2 S), a gaseous biological transmitter, has been implicated in both the physiological functions of the gastrointestinal tract and its diseases. To understand gastric epithelial cell response against H pylori infection, we investigated the metabolic changes of gastric cancer cells co-cultured with H pylori and observed the modulation of endogenous H2 S production. MATERIALS AND METHODS: Gastric cancer AGS cells were co-cultured with an H pylori standard strain possessing bacterial virulence factor CagA (ATCC 43504) and a strain without CagA (ATCC 51932). Three hours after inoculation, the cells were subjected to metabolomics analysis using gas chromatography-tandem mass spectrometry (GC-MS/MS). Orthogonal projections to latent structures discriminant analysis (OPLS-DA) and pathway analysis were performed. In addition, intracellular H2 S levels were measured by using HSip-1 fluorescent probe. RESULTS: Results of OPLS-DA showed a significant difference between the metabolism of untreated control cells and cells inoculated with the H pylori strains ATCC 51932 or ATCC 43504, mainly due to 45 metabolites. Pathway analysis with the selected metabolites indicated that methionine metabolism, which is related to H2 S production, was the most frequently altered pathway. H pylori-inoculated cells produced more endogenous H2 S than control cells. Moreover, ATCC 43504-inoculated cells produced less H2 S than ATCC 51932-inoculated cells. CONCLUSIONS: H pylori infection modulates endogenous H2 S production in AGS cells, suggesting that H2 S might be one of the bioactive molecules involved in the biological mechanisms of gastric mucosal disease including mucosal atrophy.

Successful treatment of left subclavian artery penetration due to ingestion of a safety pin by an elderly person.

BACKGROUND: Ingestion cases are increasing in elderly persons. Herein, we report a rare case of ingestion of a safety pin by an elderly person. CASE PRESENTATION: The patient was an 87-year-old bedridden woman who had fever with left pleural effusion. Chest X-ray revealed a foreign body, confirmed to be a safety pin, in the cervical esophagus. A contrast multidetector row computed tomography scan revealed that the opened safety pin penetrated the left subclavian artery, leading to the diagnosis of an esophageal foreign body penetrating the left subclavian artery. The safety pin was removed, and the subclavian artery aneurysm caused by the penetration was embolized by interventional radiology. After treatment, she was returned to the nursing home on postoperative day 8. CONCLUSION: Penetration by ingestion of a safety pin is rare; in this case, safe treatment was possible due to a team of certified specialist physicians and surgeons.

A case of the lower gastrointestinal bleeding due to Dieulafoy's ulcer in the cecum.

Gastrointestinal Dieulafoy's ulcer is a rare disease of unknown etiology. Dieulafoy's ulcer often presents in the stomach and is thought to cause about 5% of all gastrointestinal bleeds in adults, but can be found in any part of the gastrointestinal tract. Dieulafoy's ulcer corresponds to an arterial malformation in the submucosal space and can cause life-threatening hemorrhage. We report a case of the lower gastrointestinal bleeding from a cecal Dieulafoy's ulcer that was successfully treated with endoscopic clips. An 82-year-old woman had been diagnosed with hypertension and cerebral infarction. She had been using aspirin to prevent recurrent infarction. She was admitted to our hospital with hematochezia. Urgent colonoscopy revealed a small, reddish vascular malformation in the cecum. The lesion was suggestive of Dieulafoy's ulcer and was treated with endoscopic clips. The patient has since been discharged from our hospital without experiencing any further bleeding. Endoscopy is a useful method for diagnosing and treating Dieulafoy's ulcer.

Endoscopic gastric mucosal atrophy as a predictor of colorectal polyps: a large scale case-control study.

Although some studies have indicated a correlation between Helicobacter pylori infection and the risk of colorectal neoplasms, these findings have not been consistent and are controversial. This case-control study aimed to investigate the association between endoscopic gastric mucosal atrophy and colorectal polyp occurrence. Records of 7,394 participants who underwent colonoscopy examinations from August 2008 to July 2018 were reviewed retrospectively. A total of 2,404 subjects were registered; 1,565 (65.1%) were in the gastric mucosal atrophy-positive group and 1,138 (47.3%) had colorectal polyps. The multivariate analysis adjusted by age, sex, smoking habits, alcohol habits, hemoglobin A1c, and systolic blood pressure indicated that patients in the gastric mucosal atrophy-positive group more frequently had colorectal polyps compared with patients in the gastric mucosal atrophy-negative group (odds ratio, 3.27; 95% confidence interval, 2.68-4.01; p<0.001). An analysis of the association between gastric mucosal atrophy degree and colorectal polyp status indicated that, compared with mild gastric mucosal atrophy, severe gastric mucosal atrophy was associated with a higher risk of proximal colon polyps (odds ratio, 1.47; 95% confidence interval, 1.05-2.07; p = 0.024) and two or more colorectal polyps (odds ratio, 1.80; 95% confidence interval, 1.30-2.49; p<0.001). In conclusion, gastric mucosal atrophy found during esophagogastroduodenoscopy may be an indication for complete colon screening.

Differences in Helicobacter pylori and CagA antibody changes after eradication between subjects developing and not developing gastric cancer.

We evaluated serological Helicobacter pylori and cytotoxin-associated gene A (CagA) antibodies and endoscopic atrophy after eradication to identify factors predicting post-eradication gastric cancer development. Thirty-five patients with successful eradiation were divided into the post-eradication gastric cancer (13 cases) and non-gastric cancer (22 cases) groups. Serum Helicobacter pylori and CagA antibody titers and endoscopic atrophy before and six years after eradication were examined. Median Helicobacter pylori antibody titers had decreased significantly from baseline at 0.5-2 years after eradication in both groups (gastric cancer group, from 39.0 to 11.0 U/ml, p = 0.011; non-gastric cancer group, from 29.6 to 4.97 U/ml, p<0.001), but were significantly higher in the gastric cancer than in the non-gastric cancer group (p = 0.029). Median serum CagA antibody titers had also decreased significantly at 0.5-2 years after eradication (gastric cancer group, from 6.35 to 3.23 U/ml, p = 0.028; non-gastric cancer group, from 9.88 to 1.21 U/ml, p = 0.0045). Serum CagA in each group showed no significance. Endoscopic atrophy improved significantly after eradication in the non-gastric cancer, but not the gastric cancer, group (p = 0.0007). In conclusion, changes in Helicobacter pylori and CagA antibody titers and endoscopic atrophy after eradication might be useful as predictive factors for post-eradication gastric cancer.

Evaluation of a Novel Anti-H. pylori Antibody Detection Kit by Latex Turbidimetric Immunoassay.

BACKGROUND: While all modalities used for diagnosis of Helicobacter pylori (H. pylori) have demonstrated sufficient sensitivity and specificity, each test has advantages and limitations. The serum test for anti-H. pylori antibody with the latex method is noninvasive, easy, and inexpensive; it is thus a useful tool for mass-screening for H. pylori. In this study, we evaluated the utility of a newly developed latex kit, in comparison with other serum diagnostic kits based on enzyme-linked immunosorbent assay (ELISA). METHODS: In total, 187 subjects (77: H. pylori-positive, 75: H. pylori-negative, 35: previous infection with H. pylori) seen at Oita University Hospital during the period from January 1988 to September 2014 were enrolled in the study. All subjects were evaluated with 4 types of serum H. pylori antibody kits. One modality was based on the use of latex (Denka Kit, Denka Seiken Co., Ltd., Tokyo, Japan). Three kits were based on the use of ELISA. The E-Plate II Eiken (Eiken Chemical Co., Ltd., Tokyo, Japan) is henceforth referred to as Kit A. The Premier H. pylori kit (Meridian Bioscience, Inc., USA) is referred to as Kit B. The Platelia H. pylori IgG (Bio-Rad, Marnes-la-Coquette, France) is referred to as Kit C. RESULTS: Evaluation of 152 study participants, including some who were positive for H. pylori and some who were negative, sensitivity, specificity, and accuracy values were as follows: for the Denka kit, these values were, respec-tively, 92.2%, 93.3%, and 92.8%. For Kit A, these values were 88.3%, 100.0%, and 194.1%. For Kit B, these values were 98.7%, 76.0%, and 87.5%. For Kit C, these values were 98.7%, 80.0%, and 89.5%. The specificity of Kit A was > 90%. Sensitivity was > 90% for Kits B and C. For the Denka kit, both sensitivity and specificity were > 90%. Among the 35 subjects previously infected with H. pylori, the rate of positive diagnosis was 48.6% (17/35) with the Denka kit, 17.1% (6/35) with Kit A, 54.3% (19/35) with Kit B, and 54.3% (19/35) with Kit C. The rate of positive diagnosis was significantly higher with the Denka kit than with Kit A (p < 0.05). CONCLUSIONS: An assay based on use of the latex method, H. pylori-latex Seiken, demonstrated satisfactory sensitivity and specificity for detecting serum levels of H. pylori antibody. The performance of this kit was equivalent to that of ELISA kits currently used for the same purpose. This kit is therefore considered to be extremely suitable for diagnosis of H. pylori and mass-screening of patients at high risk for gastric cancer.

Examine the Availability and Safety of Mucosal Cutting Biopsy Technique for Diagnosis of Gastric Submucosal Tumor.

OBJECTIVES: Differentiating gastrointestinal stromal tumor (GIST) from other submucosal tumors (SMTs) is important in diagnosing SMT. GIST is an immunohistological diagnosis that cannot be made from images alone. Tissue sampling of tumor sites is thus becoming increasingly important. In this study, the utility and associated complications of mucosal cutting biopsy (MCB) for gastric SMTs were investigated. METHODS: This was a case series study. The subjects were patients aged ≥20 years old in whom an SMT was seen on esophagogastroduodenography and who underwent MCB between January 2012 and December 2016. Patient information, endoscopy findings, gastric SMT size, pathological diagnosis, and other information were gathered from medical records. The SMT size was the maximum diameter that could be visualized on EUS. The pathological diagnosis was made with hematoxylin-eosin staining, with immunostaining added to diagnose GIST. The endpoint was the histopathological diagnostic yield. Risk assessment using the Miettinen classification and modified Fletcher classification was also done for GISTs treated with surgery. RESULTS: The mean tumor diameter was 15.4 mm. The tumor diameter was ≥20 mm in seven patients and <20 mm in 23 patients. The tissue-acquiring rate was 93.3%. A histological diagnosis could not be made in two patients. The only complication was that bleeding required endoscopic hemostasis during the procedure in one patient, but no subsequent bleeding or no postoperative bleeding was seen. CONCLUSIONS: MCB is an appropriate and safe procedure in the diagnosis of gastric SMTs. Many hospitals will be able to perform MCB if they have the environment, including skills and equipment, to perform endoscopic submucosal dissection.

Cutaneous histopathology of the tick-bite region in severe fever with thrombocytopenia syndrome.

A case of severe fever with thrombocytopenia syndrome (SFTS) in which a skin biopsy from the tick-bite region was analyzed is reported. The patient was a 72-year-old woman who developed fever and thrombocytopenia after a tick bite. SFTS was diagnosed from polymerase chain reaction (PCR) analysis of a blood sample. Histopathological analysis of a skin biopsy specimen from the tick-bite region showed CD20-positive perivascular and interstitial immunoblastic cells, which were positive to anti-SFTS virus (SFTSV) nucleoprotein antibody. In addition, SFTSV RNA was detected by real-time PCR from this biopsy specimen. Moreover, hemophagocytosis was also found in the tick-bite region. To the best of our knowledge, this is the first report to analyze the details of the tick-bite region of skin in SFTS, and the first to detect virus-infected cells in the skin. The present findings may help elucidate the mechanisms of entry of SFTSV.

Endoscopic and Immunohistochemical Characteristics of Gastric Cancer with versus without Helicobacter Pylori Eradication.

BACKGROUND/AIMS: The rate of gastric cancer (GC) after Helicobacter pylori eradication has gradually increased; therefore, we investigate the clinicopathological features of GC following eradication in comparison with those of GC with H. pylori infection. METHODS: This study included 50 subjects with GC after eradication (GCE) and 151 patients with GC with H. pylori infection (GCI). Clinicopathological factors were assessed. The manifestation of GC was further evaluated using immunohistochemical analysis and in situ hybridization. RESULTS: Macroscopic analysis revealed a significantly higher ratio of depressed type /elevated type in the GCE compared with the GCI (30/19 vs. 61/77, p = 0.041). The gastric phenotype was more common in the GCE compared with the GCI, and the proportion of CDX2-positive cases was lower in the GCE (8 out of 18; 44.4%) compared with the GCI (18 out of 19; 94.7%; p = 0.00082). Ki-67 labeling index was significantly lower in the GCE (32.03 ± 22.15) compared with the GCI (79.20 ± 14.87, p < 0.0001). No patient in the GCE showed evidence of Epstein-Barr virus infection. CONCLUSION: The clinicopathological characteristics of GC following H. pylori eradication differ from those of GC in patients with H. pylori infection in terms of morphology, mucin phenotype, and proliferation rate.

Association between Gastric Cancer Risk and Serum Helicobacter pylori Antibody Titers.

BACKGROUND/AIMS: It is difficult to confirm the accurate cutoff value to diagnose Helicobacter pylori (Hp) infection using commercial serology kits. It is reported that there were many cases with present/past infection that even the serum Hp-IgG antibody (HpAb) titers were below the cutoff value (e.g., 10 U/mL for E-Plate®), suggesting that we might overlook many gastric cancer (GC). We investigated an association between gastric cancer risk and serum Helicobacter pylori antibody titers. METHODS: We conducted a primary screening between 2014 and 2015. We performed gastroendoscopy if HpAb titers were ≥3.0 U/mL (i.e., more than measurable limit, E-Plate). These patients were divided into two groups: HpAb = 3.0-9.9 U/mL ("negative-high" group) and HpAb ≥ 10 U/mL; cutoff value ("over-10 U/mL" group). Hp infection status was investigated, and the number of GC patients was counted. RESULTS: Among the 3321 subjects in the primary screening, 56.9% (1891/3321) showed HpAb titers ≥3.0 U/mL; 1314 patients underwent gastroendoscopy. Ten were GC. 421 patients were "negative-high" group; two were GC. After evaluating 381 patients for Hp infection, 22.6%/60.6% was with present/past infection among the "negative-high" group. CONCLUSION: We also found a correlation between HpAb titers and Hp infection status. "Negative-high" group has a risk of GC.

Rare Helicobacter pylori Virulence Genotypes in Bhutan.

Both the prevalence of Helicobacter pylori infection and the incidence of gastric cancer are high in Bhutan. The high incidence of atrophic gastritis and gastric cancer suggest the phylogeographic origin of an infection with a more virulent strain of H. pylori. More than 90% of Bhutanese strains possessed the highly virulent East Asian-type CagA and all strains had the most virulent type of vacA (s1 type). More than half also had multiple repeats in East Asian-type CagA, which are rare in other countries and are reported characteristictly found in assciation with atrophic gastritis and gastric cancer consistent with Bhutanese strains having multiple H. pylori virulence factors associated with an increase in gastric cancer risk. Phylogeographic analyses showed that most Bhutanese strains belonged to the East Asian population type with some strains (17.5%) sharing East Asian and Amerindian components. Only 9.5% belonged to the European type consistant with H. pylori in Bhutan representing an intermediate evolutionary stage between H. pylori from European and East Asian countries.

The Prevalence of Helicobacter pylori Virulence Factors in Bhutan, Vietnam, and Myanmar Is Related to Gastric Cancer Incidence.

Gastric cancer is a significant health problem in Asia. Although the prevalence of Helicobacter pylori infection is similar in Bhutan, Vietnam, and Myanmar, the incidence of gastric cancer is highest in Bhutan, followed by Vietnam and Myanmar. We hypothesized that H. pylori virulence factors contribute to the differences. The status of cagA, vacA, jhp0562, and ß-(1,3)galT(jhp0563) was examined in 371 H. pylori-infected patients from Bhutan, Vietnam, and Myanmar. Each virulence factor could not explain the difference of the incidence of gastric cancer. However, the prevalence of quadruple-positive for cagA, vacA s1, vacA m1, and jhp0562-positive/ß-(1,3)galT-negative was significantly higher in Bhutan than in Vietnam and Myanmar and correlated with gastric cancer incidence. Moreover, gastritis-staging scores measured by histology of gastric mucosa were significantly higher in quadruple-positive strains. We suggest that the cagA, vacA s1, vacA m1, and jhp0562-positive/ß-(1,3)galT-negative genotype may play a role in the development of gastric cancer.

Seroprevalence of Helicobacter pylori infection and gastric mucosal atrophy in Bhutan, a country with a high prevalence of gastric cancer.

Gastric cancer is the second leading cause of cancer-related mortality in the world. Recently, serum Helicobacter pylori antibodies and pepsinogen (PG) have been used for gastric cancer screening. The incidence of gastric cancer in Bhutan is reported to be quite high compared with that in neighbouring countries. In this study, 381 subjects from three areas of Bhutan were assessed for gastric mucosal atrophy and serological parameters. Anti-H. pylori IgG, PG I, PG II and cytotoxin-associated gene A (CagA) antibodies were measured using ELISA. Subjects were classified into four groups according to H. pylori and PG seropositivity: Group A (H. pylori-negative/PG-negative), Group B (H. pylori-positive/PG-negative), Group C (H. pylori-positive/PG-positive) and Group D (H. pylori-negative/PG-positive). The prevalence of H. pylori in the 381 subjects was 71.1% (271/381), with high infection rates found in rural areas. The PG I/II ratio was significantly inversely correlated with the atrophy score in the antrum and the corpus (P<0.001). Multivariate analysis showed that the PG status was significantly associated with the presence of atrophy in the corpus. The prevalence of the PG-positive status was significantly higher among H. pylori-positive subjects than among H. pylori-negative subjects (P<0.001). Based on the ABC method, Group B was the most dominant, followed by Group A, Group C and Group D. The high incidence of gastric cancer in Bhutan can be attributed to the high prevalence of H. pylori infection and gastric mucosal atrophy.

Intact long-type dupA as a marker for gastroduodenal diseases in Okinawan subpopulation, Japan.

BACKGROUND: Helicobacter pylori dupA can be divided into two types according to the presence or absence of the mutation. In addition, full-sequenced data revealed that dupA has two types with different lengths depend on the presence of approximately 600 bp in the putative 5' region (presence; long-type and absence; short-type), which has not been taken into account in previous studies. METHODS: A total of 319 strains isolated from Okinawa, the south islands of Japan, were included. The status of dupA and cagA was determined by polymerase chain reaction. The presence of mutations in long-type dupA was determined by DNA sequencing. RESULTS: The prevalence of long-type dupA was 26.3% (84/319). Sequence analysis showed that there were only six cases (7.1%) with point mutations lead to stop codon among 84 long-type dupA strains studied. Interestingly, intact long-type dupA without frameshift mutation, but not short-type dupA, was significantly associated with gastric ulcer and gastric cancer than gastritis (p = .001 and p = .019, respectively). After adjustment by age, gender, and cagA, the presence of intact long-type dupA was significantly associated with gastric ulcer and gastric cancer compared with gastritis (odds ratio [OR] = 3.35, 95% confidence interval [CI] = 1.55-7.24 and OR = 4.14, 95% CI = 1.23-13.94, respectively). CONCLUSIONS: Intact long-type dupA is a real virulence marker for severe outcomes in Okinawa, Japan. The previous information gained from PCR-based methods without taking long-type dupA into account must be interpreted with caution.

Helicobacter pylori cagA 12-bp insertion can be a marker for duodenal ulcer in Okinawa, Japan.

BACKGROUND AND AIM: Helicobacter pylori cagA can be classified into mainly two types (East-Asian-type and Western-type cagA) according to the repeat regions located in the 3' region. Recent studies showed that the Western-type cagA in strains from Okinawa, Japan formed a different cluster (J-Western-type cagA subtype). It has also been reported that J-Western-type cagA possesses a 12-bp insertion located in the 5' region of cagA sequence. METHODS: The prevalence of 12-bp insertion in cagA in Okinawa and the United States (U.S.) was examined by DNA sequencing. The primer pair that can detect the 12-bp insertion only by polymerase chain reaction was then designed. The prevalence of strains with 12-bp insertion was examined in 336 strains isolated from Okinawa by polymerase chain reaction. RESULTS: In case of Western-type cagA/vacA s1m2 strains, the prevalence of 12-bp insertion was significantly higher in strains isolated from Okinawa than that from the U.S. (P = 0.002). Phylogenetic tree showed that strains with 12-bp insertion formed two individual clusters within J-Western-type cagA subtype; one is from Okinawa and another is from the U.S. The designed primer set showed high sensitivity (100%) and specificity (90.8%) in Okinawa. The 12-bp insertion was found in 23.7%, 14.3%, 4.2%, and 4.0% of strains with duodenal ulcer (DU), gastritis, gastric cancer, and gastric ulcer (GU), respectively (P < 0.001 for DU vs GU) in Okinawa. CONCLUSIONS: Although the mechanisms are unknown, the presence of 12-bp insertion was associated with the presence of DU and might have a suppressive action on GU and gastric cancer.

Helicobacter pylori iceA, clinical outcomes, and correlation with cagA: a meta-analysis.

BACKGROUND: Although the iceA (induced by contact with epithelium) allelic types of Helicobacter pylori have been reported to be associated with peptic ulcer, the importance of iceA on clinical outcomes based on subsequent studies is controversial. The aim of this study was to estimate the magnitude of the risk for clinical outcomes associated with iceA. METHODS: A literature search was performed using the PubMed and EMBASE databases for articles published through April 2011. Published case-control studies examining the relationship between iceA and clinical outcomes (gastritis, peptic ulcer, including gastric ulcer and duodenal ulcer, and gastric cancer) were included. RESULTS: Fifty studies with a total of 5,357 patients were identified in the search. Infection with iceA1-positive H. pylori increased the overall risk for peptic ulcer by 1.26-fold (95% confidence interval [CI], 1.09-1.45). However, the test for heterogeneity was significant among these studies. Sensitivity analysis showed that the presence of iceA1 was significantly associated with peptic ulcer (odds ratio [OR] = 1.25, 95% CI = 1.08-1.44). The presence of iceA2 was inversely associated with peptic ulcer (OR = 0.76, 95% CI = 0.65-0.89). The presence of iceA was not associated with gastric cancer. Most studies examined the cagA status; however, only 15 studies examined the correlation and only 2 showed a positive correlation between the presence of cagA and iceA1. CONCLUSION: Our meta-analysis confirmed the importance of the presence of iceA for peptic ulcer, although the significance was marginal.