Eradication Therapy for Helicobacter pylori Infection in Patients Receiving Hemodialysis: Review.

Patients receiving hemodialysis (HD) often develop gastrointestinal diseases. Recently, although in general population, clinical guidelines for Helicobacter pylori have strongly recommended its eradication in patients to prevent gastric cancer, optimal eradication regimen and optimal dosage of drugs for patients receiving HD have not been established, due to possible incidence of adverse events. Some antimicrobial agents used in eradication therapy, particularly amoxicillin, can exacerbate renal dysfunction. Given the delayed pharmacokinetics of drugs in patients receiving HD compared with those in healthy individuals, drug regimen and dosage should be considered to minimize adverse effects. Although previous studies have investigated the benefits of eradication therapy for patients receiving HD, because most studies were small in terms of the number of enrolled patients, it is hard to show evidence. The numbers of eradication in HD patients have recently increased, and it is important to provide an optimal regimen. The consideration of eradication in patients undergoing HD with a reduction in the drug dose by 1/2-1/3 may prevent adverse events. Additionally, another important consideration is whether adverse events can be prevented while maintaining a similar eradication rate with reduced drug dosages. Recent meta-analysis findings indicate comparable eradication rates in patients receiving HD and healthy individuals, both with the same dosage regimen and at a reduced dosage regimen, with no significant differences (relative risk [RR] for successful eradication: 0.85 [95% confidence interval (CI): 0.48-1.50]). Unlike with the same dosage regimen (RR for adverse events: 3.15 [95% CI: 1.93-5.13]), the adverse events in the dosage reduction regimen were similar to those in healthy individuals (RR: 1.26 [95% CI: 0.23-6.99]). From a pharmacological perspective, the eradication regimen in patients receiving HD should consider the dosage (1/2-1/3 dosage), dosing number (bid), dosing timing of drugs (after HD), and susceptibility to antimicrobial agents.

Evaluation of the effects of a proton pump inhibitor on Helicobacter pylori stool antigen testing.

BACKGROUND: Some patients find it difficult to discontinue proton pump inhibitors (PPIs). Unlike the 13 C-urea breath test (UBT), the stool antigen test (SAT), particularly when domestically produced kits are used, may be less likely to yield false-negative results. METHODS: This prospective study included a convenience series of 35 healthy Japanese subjects. Based on a statistical calculation, acceptable numbers of subjects were considered at least 21 and 11 with and without Helicobacter pylori (H. pylori) infection, respectively. The H. pylori infection was determined using the UBT or rapid urease test. SATs were performed with three novel domestically produced kits (the rapid immunochromatography tests Quick Navi™-H. pylori [Navi™] and Quick Chaser® H. pylori [Chaser®], and the bioluminescent enzyme immunoassay test BLEIA® 'EIKEN' H. pylori Antigen [BLEIA®]) before and after oral PPI administration (30 mg lansoprazole once daily for 14 days). For each kit, the sensitivities and specificities were calculated and compared before and after PPI administration. Furthermore, the cutoff index (COI) values of BLEIA® before and after PPI administration were compared in H. pylori-infected subjects. RESULTS: H. pylori infection was detected in 68.6% (24/35) of the included subjects. The sensitivities and specificities before versus after PPI administration were as follows: 79.2% (19/24) and 100.0% (11/11) versus 75.0% (18/24) and 100.0% (11/11) for Navi™, respectively (p = 1); 87.5% (21/24) and 100.0% (11/11) versus 75.0% (18/24) and 100.0% (11/11) for Chaser®, respectively (p = .371); 100.0% (24/24) and 100.0% (11/11) versus 95.8% (23/24) and 100.0% (11/11) for BLEIA®, respectively (p = 1). The median COI values of BLEIA® before and after PPI administration were 1389.0 and 3207.25, respectively (p = .0839). CONCLUSIONS: In stool specimens, H. pylori antigenicity is maintained even during PPI use. SAT using a bioluminescent enzyme immunoassay is particularly recommended because of its extremely high sensitivity.

PCR analysis and specific immunohistochemistry revealing a high prevalence of non-Helicobacter pylori Helicobacters in Helicobacter pylori-negative gastric disease patients in Japan: High susceptibility to an Hp eradication regimen.

BACKGROUND: The clinical significance of non-Helicobacter pylori Helicobacter (NHPH) is still unknown. There are many reports of NHPH-infected patients suffering from gastric diseases. Here, we investigated the polymerase chain reaction (PCR) positivity of NHPH infection in gastric disease patients who were negative for H. pylori (Hp) by the rapid urease test and by pathological observation. MATERIALS AND METHODS: We collected the 296 endoscopically obtained gastric mucosal samples of Hp-negative gastric disease patients diagnosed based on a rapid urease test and pathology from 17 hospitals in Japan from September 2013 to June 2019, and we analyzed the existence of Hp and NHPH by PCR. The samples were also treated by indirect immunohistochemistry using an anti-Helicobacter suis VacA paralog antibody and were observed by confocal laser microscopy. RESULTS: Among the 236 non-Hp-eradicated cases, 49 cases (20.8%) were positive for NHPH. Among them, 20 cases were positive for Helicobacter suis, 7 cases were positive for Helicobacter heilmannii sensu stricto/ Helicobacter ailurogastricus (Hhss/Ha), and the other 22 cases could not be identified. The regional differences in the infection rates were significant. Forty percent of the nodular gastritis cases, 24% of the MALT lymphoma, 17% of the chronic gastritis cases, and 33% of the gastroduodenal ulcer cases were NHPH positive. Forty-five patients had been treated with one of the four types of combinations of a proton pump inhibitor and two antibiotics, and in all of these cases, the NHPH diagnosed by PCR was successfully eradicated. Immunohistochemistry using the Helicobacter suis-specific HsvA antibody coincided well with the PCR results. Among the 29 post-Hp eradication cases, three were NHPH positive, including one Hhss/Ha-positive case. Thus, approx. 20% of the Hp-negative non-Hp-eradicated gastric disease patients treated at 17 hospitals in Japan were infected with NHPH.

Influence of Helicobacter pylori Infection and Atrophic Gastritis on the Gut Microbiota in a Japanese Population.

BACKGROUND: Although infection with Helicobacter pylori and subsequent atrophic gastritis modulate the gastric conditions, their relationship with the gut microbiota in -Japanese population has not been clearly characterized. METHODS: A cohort of 1,123 subjects who participated in a health survey was studied. Infection of H. pylori was defined by both serum antibody and stool antigen test. The presence and severity of atrophic gastritis were defined by serum levels of pepsinogens. The relative abundance of each bacterial species in fecal samples was calculated by using 16S ribosomal RNA amplification, and the composition ratios of bacterial taxa were evaluated using propensity score matching. RESULTS: The abundance of 3 orders, 4 families, and 4 genera was significantly higher in H. pylori-infected subjects than in noninfected subjects (false discovery rate [FDR] <0.05). In H. pylori-infected subjects with severe atrophic gastritis, the abundance of the class Bacilli, order Lactobacillales, family Streptococcaceae, and genus Streptococcus was significantly higher than that in H. pylori-infected subjects without atrophic gastritis (FDR < 0.05). CONCLUSIONS: A significant increase in the relative abundance of several taxa was observed in gut microbiota of Japanese subjects with H. pylori infection. Among the subjects with severe atrophic gastritis, the increase in the genus Streptococcus is a remarkable characteristic.

Guidelines for the management of Helicobacter pylori infection in Japan: 2016 Revised Edition.

BACKGROUND: Since "Helicobacter pylori (H. pylori) infection" was set as the indication in the Japanese Society for Helicobacter Research (JSHR) Guidelines 2009, eradication treatment for H. pylori gastritis is covered under insurance since 2013 in Japan, and the number of H. pylori eradication has rapidly increased. Under such circumstances, JSHR has made the third revision to the "Guidelines for diagnosis and treatment of H. pylori infection" for the first time in 7 years. METHODS: The Guideline Committee held 10 meetings. Articles published between the establishment of the 2009 Guidelines and March 2016 were reviewed and classified according to the evidence level; the statements were revised on the basis of this review. After inviting public comments, the revised statements were finalized using the Delphi method. RESULTS: There was no change in the basic policy that H. pylori infectious disease is an indication for eradication. Other diseases presumed to be associated with H. pylori infection were added as indications. Serum pepsinogen level, endoscopic examination, and X-ray examination were added to the diagnostic methods. The effects of 1-week triple therapy consisting of potassium-competitive acid blocker (P-CAB), amoxicillin, and clarithromycin have improved, and high eradication rates can also be expected with proton pump inhibitors (PPI) or P-CAB combined with amoxicillin and metronidazole. If the susceptibility test is not performed, the triple PPI or P-CAB/amoxicillin/metronidazole therapy should be chosen, because the PPI/amoxicillin/metronidazole combination demonstrated a significantly higher eradication rate than PPI/amoxicillin/clarithromycin. In the proposal for gastric cancer prevention, we divided gastric cancer prevention measures by age from adolescent to elderly, who are at an increased gastric cancer risk, and presented measures for gastric cancer prevention primarily based on H. pylori eradication. CONCLUSION: We expect the revised guidelines to facilitate appropriate interventions for patients with H. pylori infection and accomplish its eradication and prevention of gastric cancer.

Influence of gastric endoscopic submucosal dissection on serum opsonic activity measured by chemiluminescence.

This study aimed to elucidate whether changes in serum opsonic activity measured by lucigenin-dependent chemiluminescence and luminol-dependent chemiluminescence are useful for estimating physical stress during the perioperative period of gastric endoscopic submucosal dissection. Serum opsonic activity in the peripheral blood of 87 patients was examined in the morning of the day of endoscopic submucosal dissection, the next day, and at 4 days after endoscopic submucosal dissection. Peak height and area under the curve for lucigenin-dependent chemiluminescence were 106.1 ± 22.7% and 102.0 ± 24.7% on the day of endoscopic submucosal dissection, which increased significantly to 113.6 ± 29.4% and 111.0 ± 29.1% on the next day (both p<0.01), and 112.4 ± 27.0% and 110.0 ± 28.1% at 4 days after endoscopic submucosal dissection (both p<0.01), respectively. In contrast, significant changes were not observed in peak height and area under the curve for luminol-dependent chemiluminescence during the perioperative period of endoscopic submucosal dissection. This difference suggests that serum opsonic activity during the perioperative period of gastric endoscopic submucosal dissection is associated with the production of substances with lower oxidizing potential. (The study of changes in neutrophil function and physical stress during the perioperative period of endoscopic operation: UMIN000034514).

Estimation of perioperative invasiveness of colorectal endoscopic submucosal dissection evaluated by energy metabolism.

The aim of this study was to assess the perioperative invasiveness of endoscopic submucosal dissection for colorectal cancer quantitatively by using energy metabolism. In fifty-three patients who underwent endoscopic submucosal dissection for colorectal cancer, resting energy expenditure using an indirect calorimeter, body weight and basal energy expenditure using the Harris-Benedict equation before and after endoscopic submucosal dissection. Resting energy expenditure/body weight and resting energy expenditure/basal energy expenditure were 19.7 ± 2.5 kcal/kg/day and 0.96 ± 0.12 on the day of endoscopic submucosal dissection, whereas one day after the endoscopic submucosal dissection they increased to 21.0 ± 2.9 kcal/kg/day and 1.00 ± 0.13 (p<0.001 and p<0.05, respectively). The stress factor on the postoperative day 1 was computed as 1.06. The increase was lower comparing with that experienced for surgery, suggesting that the perioperative invasiveness of colorectal endoscopic submucosal dissection is lower in comparison to that during surgery. Furthermore, in spite of technical difficulty, stress factor of colorectal endoscopic submucosal dissection was approximately equal to that of gastric endoscopic submucosal dissection. (The study of the resting energy metabolism and stress factor using an indirect calorimeter in the perioperative period of endoscopic operation: UMIN000027135).

Analysis of the cost-effectiveness of using vonoprazan-amoxicillin-clarithromycin triple therapy for first-line Helicobacter pylori eradication.

BACKGROUND: Vonoprazan (VPZ)-based triple therapy has been reported to have greater efficacy than a proton pump inhibitor (PPI)-based triple therapy for Helicobacter pylori (H. pylori) eradication. However, because VPZ is more expensive than PPIs such as rabeprazole (RPZ), economic evaluation is essential. METHODS: We performed a retrospective study on 209 patients who underwent first-line eradication of H. pylori infection in Fuyoukai Murakami Hospital from 1 March 2015 to 31 March 2016. Patients who received VPZ, amoxicillin (AMPC) and clarithromycin (CAM) were assigned to the VPZ/AC group (n = 111) and patients who received RPZ, AMPC and CAM to the RPZ/AC group (n = 98). We compared the patients' backgrounds, including age, gender, use of high-dose CAM, past history of peptic ulcer, smoking and drug-related adverse events between the two groups. We defined cost as direct medical costs per patient and effectiveness as the first-line eradication rate in the intention-to-treat (ITT) analysis and analyzed the cost-effectiveness using the cost-effectiveness ratio (CER) and incremental cost-effectiveness ratio (ICER). RESULTS: There was no significant difference in the patients' backgrounds. The ITT analysis revealed an eradication rate of 94.6% for VPZ/AC and 86.7% for RPZ/AC. VPZ/AC cost 1155.4 Japanese yen (JPY) higher than RPZ/AC (34063.4 vs. 32908.0, JPY). CER of VPZ/AC was less than that of RPZ/AC (360.1 vs. 379.4, JPY per percent) and ICER of VPZ/AC was 147.0 JPY (1.28 Euro (EUR), 1 EUR =115 JPY) per percent. CONCLUSIONS: VPZ/AC was more cost-effective than RPZ/AC as first-line therapy for H. pylori eradication.

Decrease of Estradiol and Several Lifestyle Factors, but Not Helicobacter pylori Infection, Are Significant Risks for Osteopenia in Japanese Females.

BACKGROUND: The primary cause of osteoporosis in women is increased bone resorption and decreased bone density associated with reduced estrogen secretion. Several studies have demonstrated a relationship between Helicobacter pylori infection and osteoporosis regardless of estrogen levels. This study examined the relationship between H. pylori infection and osteopenia together with estrogen levels, calcium intake, and several lifestyle factors. METHODS: This study included 473 healthy women who underwent a general health examination. Multivariate analysis was performed, with age, body mass index (BMI), smoking habit, drinking habit, exercise habit, schooling duration, estradiol levels, birth history, calcium intake, schooling duration, smoking habit, drinking habit, exercise habit, and H. pylori infection as independent variables and the presence of osteopenia as a dependent variable. RESULTS: The adjusted OR for osteopenia with H. pylori infection was 0.95 (95% CI 0.55-1.63, p = 0.84). In contrast, osteopenia was significantly associated with age, low BMI, lesser schooling period, low estradiol levels, and low calcium intake. CONCLUSIONS: H. pylori infection was not a significant risk for osteopenia by the multivariate analysis, which included the primary confounding factors. Significant factors, such as estradiol and calcium intake, should be assessed together to study the association of H. pylori infection and osteopenia.

Energy metabolism during the perioperative period of gastric endoscopic submucosal dissection.

The aim of this study was to investigate the change in the energy metabolism and invasiveness in the perioperative period of endoscopic submucosal dissection for early gastric cancer. Fifty-two consecutive patients were enrolled into the study between July 2013 and May 2014 and examined resting energy expenditure using an indirect calorimeter, body weight and basal energy expenditure using the Harris-Benedict equation before and after endoscopic submucosal dissection. Resting energy expenditure/body weight and resting energy expenditure/basal energy expenditure were 20.2 ± 3.0 kcal/kg/day and 0.96 ± 0.11 on the day of endoscopic submucosal dissection, whereas one day after the endoscopic submucosal dissection they were 21.7 ± 3.2 kcal/kg/day and 1.03 ± 0.14, showing significant increases (p<0.001, respectively). The stress factor on the postoperative day 1 was computed as 1.07. This increase was low in comparison to that experienced for surgery, suggesting that the degree of perioperative invasiveness in patients receiving endoscopic submucosal dissection is lower in comparison to that during surgery (The study of the resting energy metabolism and stress factor using an indirect calorimeter in the perioperative period of endoscopic operation: UMIN000027135).

Study of the mechanisms of a Japanese traditional fermented medicine in the improvement of constipation.

BACKGROUND AND AIM: Gut Working Tablet (GWT) is a Japanese traditional fermented medicine based on Aspergillus oryzae NK-fermented grain germ. Although GWT has been used by patients with constipation, the mechanism has not been investigated. The aim of this study was to examine the possible mechanisms of the effect of GWT on constipation. METHODS: The effect of GWT water extracts on gut contractility using ileum strips from guinea pig and on the growth of Bifidobacterium longum were examined in vitro. The 14 Sprague Dawley rats were administered loperamide at 10 mg/day per kg for 3 days. They were fed with and without 5% of GWT before and during administration of loperamide. Number of stools and weight of feces were measured before and during administration of loperamide. The concentrations of short-chain fatty acids (SCFAs) in the feces and cecal contents were measured by gas chromatography. RESULTS: GWT water extracts dose-dependently induced ileal contractile responses, which were inhibited by atropine. The growth of B. longum was increased in the presence of GWT water extracts in a dose-dependent manner (P < 0.01 vs control). The decrease in both the number and weight of feces caused by loperamide was improved by GWT administration (P < 0.05 vs loperamide). The decrease in the butyric acid concentration in feces and cecal contents induced by the administration of loperamide was inhibited by GWT (P = 0.035 and 0.018). CONCLUSION: GWT water extracts may induce cholinergic-like stimulation and promote the growth of probiotics. Furthermore, GWT water extract contributed to normalization of colonic SCFAs. These results may explain, at least in part, the beneficial effects of GWT on constipation.

Bortezomib induces thrombocytopenia by the inhibition of proplatelet formation of megakaryocytes.

Bortezomib is a potent proteasome inhibitor that has been extensively used to treat multiple myeloma. One of the most common grade 3 adverse events is cyclic thrombocytopenia. In this study, we studied the mechanism by which bortezomib induces thrombocytopenia in a mouse model. After the intravenous administration of bortezomib (2.5 mg/kg) via tail vein, platelet counts significantly decreased on days 2-4 and recovered to the normal range on day 6. Bortezomib (2.5 mg/kg) injected into mice in vivo did not affect colony-forming unit-megakaryocytes (CFU-Mk) or megakaryocytes in the bone marrow. However, proplatelet formation (PPF) significantly decreased on days 2 and 4, after bortezomib administration to mice. Meanwhile, CFU-Mk formation and the ploidy distribution of cultured megakaryocytes in vitro were not affected by bortezomib used at concentrations of ≤ 1 ng/mL. The PPF of megakaryocytes in vitro significantly decreased with 0.1, 1, 10, and 100 ng/mL bortezomib. Considering the bortezomib concentration in clinical studies, these data strongly suggest that decreased PPF activity induces thrombocytopenia. To elucidate the mechanism behind decreased PPF, Western blot was performed. Activated Rho expression increased after the incubation of murine platelets with bortezomib. Decreased PPF activity was eliminated by the addition of Y27632, a Rho kinase inhibitor, in vitro. Given that the Rho/Rho kinase pathway is a negative regulator of PPF, bortezomib increases activated Rho, inducing decreased PPF, which results in decreased platelet count.

Prevalence of Helicobacter pylori infection by birth year and geographic area in Japan.

BACKGROUND: Helicobacter pylori (H. pylori)-related diseases are responsible for a tremendous amount of morbidity and mortality in Japan. We estimated the prevalence of H. pylori infection by sex, birth year, and geographic area among Japanese adults. MATERIALS AND METHODS: This cross-sectional study included 14,716 subjects aged 20 years or more who underwent a health checkup between May 1997 and March 2013 in seven geographic areas throughout Japan. Relevant information on the demographics and status of H. pylori infection was retrieved from the electronic database. The univariate log-binominal regression model was used to estimate the prevalence of H. pylori infection, taking birth year into consideration. The multivariate log-binominal regression model was used to compare the prevalence of H. pylori infection between seven geographic areas. RESULTS: The overall prevalence of H. pylori infection was 37.6% in women and 43.2% in men. Among seven geographic areas, Hokkaido showed the lowest prevalence (29.4%), while Yamagata Prefecture represented the highest (54.5%). The prevalence of H. pylori infection was highest in the 1940-1949 birth cohort and then decreased in the ensuing birth cohorts; the risk ratio (RR) was 0.85 (95% confidence interval (CI) 0.84-0.87) for changes in the 10-year birth cohort. Individuals in Yamagata Prefecture had the highest RR of acquiring H. pylori infection in all three birth cohorts (RR = 1.53 for 1940, RR = 1.69 for 1950, and RR = 1.85 for 1960) when compared with those in Hokkaido. CONCLUSIONS: The prevalence of H. pylori infection increases with age and exhibits geographic variation in Japan. There has been a striking decrease in the prevalence of H. pylori infection, especially in younger Japanese populations.

Decrease of serum level of gastrin in healthy Japanese adults by the change of Helicobacter pylori infection.

BACKGROUND AND AIM: In Japan, the prevalence of Helicobacter pylori infection is decreasing and the number of patients who receive eradication therapy is increasing. Although the serum level of gastrin is affected by H. pylori infection, the normal level has been unchanged for more than 20 years. The aim of this study was to study whether the present normal range for the serum gastrin level is appropriate for Japanese at present or in the near future. METHODS: We studied 810 adults (40-80 years old) who participated in a health survey in 2012. We measured H. pylori stool antigen, titer of serum antibody to H. pylori, and serum level of gastrin. The patient's H. pylori status was defined as positive or negative when the results of both stool antigen and serology were concordant. Subjects who were taking proton-pump inhibitor and had a previous history of gastric surgery were excluded. RESULTS: Mean serum level of gastrin was 66.2±49.6 pg/mL in 281 H. pylori-negative subjects and 69.7±42.2 pg/mL in 115 patients who had H. pylori eradicated at least 2 years ago. The level of gastrin was 134.4±145.6 pg/mL in 224 patients with H. pylori infection and the level was significantly higher when compared with those in uninfected subjects and eradicated patients (P<0.01). CONCLUSIONS: Because the situation of H. pylori infection has changed remarkably in Japan, a new appropriate normal range of gastrin should be established using current Japanese populations.

[H. pylori infection and lifestyle related diseases].

The association between Helicobacter pylori infection and lifestyle related diseases was examined in a health survey. The results suggested that 1) infection of H. pylori would accelerate the progress of atherosclerosis in elderly men who smoke, 2) severe atrophic gastritis caused by H. pylori infection would have a significant association with the decrease in serum lipid level, 3) H. pylori infection was a decreased risk for tooth loss in healthy men, and 4) H. pylori infection was not associated with osteopenia in elderly. Since, clinical features, such as proportion of cagA-positive strains and frequency of severe atrophic gastritis in elderly are different between Western populations and Japanese, further studies based on Japanese patients are required to determine the association between H. pylori infection and lifestyle related diseases.

Assessment of the Physical Invasiveness of Peroral Endoscopic Myotomy during the Perioperative Period Based on Changes in Energy Metabolism.

A novel treatment method for achalasia of the esophagus and related disorders is known as peroral endoscopic myotomy (POEM). This study aimed to calculate the resting energy expenditure (REE) and evaluated the degree of physical invasiveness based on metabolic changes during the perioperative period of POEM. Fifty-eight patients who underwent POEM were prospectively enrolled; REE, body weight (BW), and basal energy expenditure were measured on the day of POEM, postoperative day 1 (POD 1), and three days after POEM (POD 3). The median REE/BW increased from 19.6 kcal/kg on the day of POEM to 24.5 kcal/kg on POD 1. On POD 3, it remained elevated at 20.9 kcal/kg. The stress factor on POD 1 was 1.20. Among the factors, including the Eckardt score, operation time, and the length of myotomy, the length of myotomy was associated with changes in REE/BW. During the perioperative period of POEM, the level of variation in energy expenditure was lower than that of esophageal cancer surgeries performed under general anesthesia. However, because the length of myotomy is a factor affecting changes in energy expenditure, careful perioperative management is desirable for patients with longer myotomy lengths.

ABC screening for gastric cancer is not applicable in a Japanese population with high prevalence of atrophic gastritis.

A combination of the detection of serum anti-Helicobacter pylori antibody and measurement of the level of serum pepsinogens (PG)s, known as the ABC method, has been used in screening for gastric cancer. The ABC method has been shown to be useful in urban and/or younger populations. The aim of this study was to assess whether this method is applicable for an agricultural population with a high incidence of gastric cancer. In all, 1048 healthy adults (401 men and 647 women) who participated in a mass survey in April 2005 were examined. Their serum samples were tested to determine the prevalence of anti-H. pylori antibody, and the levels of PG I and PG II were also measured to assess the presence of atrophic gastritis. Of the elderly subjects born before 1940, 59.4% were classified into groups C and D, with a high risk for gastric cancer, and only 22.7% were classified into group A, with the lowest risk. Of the middle-aged subjects born in the 1940s and the 1950s, 66.5% were classified into groups B-D. If the ABC method is performed in the mass screening for gastric cancer in this population, a large number of subjects will be identified for further examinations. The applicability of the ABC method should be evaluated before use in the screening for gastric cancer, particularly in an aging population with a high prevalence of H. pylori infection and atrophic gastritis.

Characterization and usefulness of stool antigen tests using a monoclonal antibody to Helicobacter pylori catalase.

BACKGROUND AND AIM: Two types of stool antigen tests have been used in the management of Helicobacter pylori infection. Testmate Pylori Antigen enzyme immunoassay (TPAg EIA) is a direct sandwich enzyme immunoassay (EIA) while Testmate Rapid Pylori Antigen (Rapid TPAg) is performed using immunochromatography. The aim of this study was to study the characterization and usefulness of these tests. METHODS: Accuracy of both tests was studied using 111 fecal samples obtained from H. pylori-positive or -negative patients. Cross-reactivity was examined with four other Helicobacter spp. and five fecal bacteria in humans. To estimate the sensitivity of both kits, we tested H. pylori clinical strains. We also examined the diagnostic performances of both tests after the storage for 12 months. RESULTS: The accuracy of both Testmate kits was 100% in fecal samples from 111 patients. No cross-reactivity was observed in both Testmate kits in five fecal bacteria and four other Helicobacter spp. TPAg EIA and Rapid TPAg showed positive results in 1342 of 1344, and 483 of 485 clinical strains, respectively. Diagnostic performances was maintained for 12 months when TPAg EIA was stored at 4°C and Rapid TPAg at 30°C. CONCLUSIONS: We examined the details of high accuracy of TPAg EIA and Rapid TPAg. The diagnostic performance of both kits was maintained after storage for up to 1 year. The two types of tests would be useful in the management of H. pylori infection.

Evaluation of the clinical relevance of hrgA gene in patients with Helicobacter pylori infection.

BACKGROUND/AIMS: Patients with gastric cancer in some Asian populations were infected more frequently with hrgA-positive H. pylori. The aim of this study was to examine the usefulness of hrgA to predict the clinical outcome of H. pylori infection. METHODOLOGY: Forty four patients with gastric cancer (35 intestinal and 9 diffuse type cancer) and 51 control subjects were studied. Presence of hrgA gene in H. pylori strains isolated from biopsy specimens was examined by PCR. Biopsy specimens were also obtained for histological assessment of gastritis. RESULTS: Nine of 44 patients with gastric cancer (20.4%) and 11 of 51 control subjects (21.6%) were infected with hrgA-positive strain (NS). In patients with gastric cancer, prevalence of hrgA-positive strain was 20.0% in patients with intestinal type cancer (7/35) and 22.2% with diffuse type cancer (2/9) (NS). In control subjects, the prevalence of hrgA-positive infection was not associated with gastric mucosal inflammatory infiltration and glandular atrophy. CONCLUSIONS: Infection with hrgA-positive strain was not frequent among patients with gastric cancer. Presence of hrgA gene would not be a useful marker to predict clinical outcome of patients infected with H. pylori in this series of Japanese patients.

Influence of endoscopic submucosal dissection on serum levels of pepsinogens in patients with early gastric cancer.

BACKGROUND: The serum levels of pepsinogens (PG) have been considered to be a useful marker for assessing the risk of metachronous gastric cancer in patients who undergo endoscopic submucosal dissection. However, the influence of endoscopic submucosal dissection (ESD) on serum levels of PG has not yet been examined. The aim of this study was to examine whether the level of PG after ESD can be used to predict the risk of metachronous cancer. PATIENTS AND METHODS: The study included of 100 consecutive patients who underwent ESD for gastric cancer at Hirosaki University Hospital from September 2009 to February 2011. Serum levels of PG I and II on the day before and after ESD were compared. Stool antigen test was also performed to examine the presence of Helicobacter pylori infection. RESULTS: The mean serum level of PG I before and after ESD was 34.3 ± 31.6 ng/mL and 70.5 ± 100.0 ng/mL (P < 0.001), respectively. PG I/II ratio before and after ESD was 2.40 ± 1.51 and 2.79 ± 1.70 (P < 0.001). The serum level of PG I and the PG I/II ratio were significantly changed after ESD, regardless of the use of proton pump inhibitor, Helicobacter pylori infection or the location of the tumor. CONCLUSIONS: ESD treatment modulates the serum level of PG I and significantly increases the PG I/II ratio. Serum levels of PG should be measured before the ESD procedure is performed to predict the risk of developing metachronous gastric cancer after ESD.