Pitavastatin Compared with Differential Intervention Trial by Standard Therapy on Cardiovascular Events in Patients with Dyslipidemia on Chronic Hemodialysis (DIALYSIS): A Randomized Controlled Trial.

INTRODUCTION: Statin has been reported to reduce cardiovascular events. However, the comparative efficacy of statin with standard therapy on cardiovascular events has not been sufficiently reported in patients on chronic hemodialysis. Thus, this study aimed to compare the effects of pitavastatin and standard therapy on mortality and cardiovascular events in chronic hemodialysis patients with dyslipidemia in Japan. METHODS: Patients on chronic hemodialysis with dyslipidemia were randomized into pitavastatin-administered (pitavastatin group) or dietary therapy as standard therapy (control) group. Primary outcomes are all-cause mortality and myocardial infarction; secondary outcomes are cardiac arrest and fatal myocardial infarction. The composite outcomes included the incidence of coronary intervention, stroke, fracture, and hospitalization due to heart failure and unstable angina. The clinical outcome analyses used a logistic regression model to categorize the variables. A p value of <0.05 was considered statistically significant. RESULTS: This study included 848 patients (422 in the control group and 426 in the pitavastatin group) from 79 health facilities. The mean age of the patients was 60.1±10.3 years, and the dialysis period was 7.2±7.6 years. The mean observation period was 36.5 months. The low-density lipoprotein cholesterol level was significantly lower than the baseline value in the pitavastatin group after 12 months of trial (79.8±26.1 vs. 107.8±25.5 mg/dL, p < 0.001). Moreover, the total number of deaths was 85, of which 50 occurred in the control group and 35 in the pitavastatin group. In an analysis adjusted for confounding factors due to participant attributes, there was a significant difference between the control group and the pitavastatin group in the primary and composite endpoints (p = 0.007 and p = 0.022, respectively). CONCLUSION: Our study has demonstrated that aggressive intervention with pitavastatin is more effective than the standard (dietary) therapy for improving the clinical outcomes in patients with dyslipidemia on chronic hemodialysis.

Association between maternal use of spray formulations and offspring urological anomalies: The Japan Environment and Children's Study.

OBJECTIVE: Concerns exist regarding the effects of maternal inhalation of household products on fetal health. This study aimed to clarify the impact of maternal exposure to household products, including spray formulations, on urological anomalies in offspring up to the age of 1 year. METHODS: This study included data from 84 237 children from the Japan Environment and Children's Study, an ongoing nationwide cohort study. Using maternal self-report questionnaires, information on the use of organic solvents, waterproof sprays, insect-repellent sprays, insecticide sprays, and herbicides from implantation until the second or third trimester of pregnancy and data on urological anomalies were collected 1 year after delivery. RESULTS: Urological anomalies occurred in 799 infants. Multivariate logistic regression analysis adjusted for maternal age, pregnancy body mass index, gestational diabetes, pre-existing maternal kidney disease, and preterm birth revealed no association between maternal exposure to organic solvents and the prevalence of offspring urological anomalies. Nevertheless, we observed significant associations between waterproof spray use during pregnancy and urological anomalies in boys (odds ratio [OR]: 1.28, 95% confidence interval [CI]: 1.03-1.59) and between the use of insecticide spray during pregnancy and urological anomalies in girls (OR: 1.48, 95% CI: 0.98-2.22). Sub-analysis revealed significant associations between waterproof spray use during pregnancy and vesicoureteral reflux in boys (OR: 2.14, 95% CI: 1.02-4.49) and between the use of insecticide spray during pregnancy and hydronephrosis in girls (OR: 2.23, 95% CI: 1.11-4.47). CONCLUSION: Spray formulation use during pregnancy might increase the risk of urological anomalies in the offspring.

Lifetime incidence risk for gastric cancer in the Helicobacter pylori-infected and uninfected population in Japan: A Monte Carlo simulation study.

Helicobacter pylori (H. pylori) infection is considered the leading cause of gastric cancer. Gastric cancer is currently a common cancer with high incidence and mortality rates, but it is expected that the incidence rate will gradually decrease as the H. pylori infection prevalence decreases in the future. When evaluating the effectiveness of gastric cancer prevention strategies, it is essential to note the differences in long-term cumulative risks between H. pylori-infected and uninfected populations, but this has not yet been precisely evaluated. In our study, we aimed to estimate the cumulative incidence risks of developing gastric cancer from birth to 85 years among H. pylori-infected and uninfected populations by using population-based cancer registry data and birth year-specific H. pylori infection prevalence rates. Death from gastric cancer and other causes of death were considered in the estimations of the adjusted cumulative incidence risks stratified by sex and H. pylori infection status. After performing 5000 Monte Carlo simulations with repeated random sampling using observed cancer incidence in selected three prefectures (Fukui, Nagasaki, Yamagata) of prefectural population-based cancer registry in Japan, the mean adjusted cumulative incidence risk for gastric cancer in the H. pylori-infected population was 17.0% for males and 7.7% for females and 1.0% for males and 0.5% for females in the uninfected population. These results calculated with Japanese cancer registry data may be useful in considering and evaluating future prevention strategies for gastric cancer in Japan.

Prevalence estimates of Helicobacter species infection in pancreatic and biliary tract cancers.

BACKGROUND: Helicobacter pylori infection is a well-established risk factor for gastric cancer and has been linked to other gastrointestinal diseases, including pancreatic and biliary tract cancers; however, the relevance of enterohepatic non-H. pylori helicobacters to the pathophysiology of these diseases remains unclear. MATERIALS AND METHODS: We estimated the prevalence of two enterohepatic non-H. pylori helicobacters (Helicobacter hepaticus and Helicobacter bilis) in the framework of a hospital-based case-control study involving 121 patients with biliary tract cancer, pancreatic cancer, or other gastrointestinal diseases. Bile and blood samples were collected from the patients undergoing endoscopic retrograde cholangiopancreatography. The presence of H. bilis, H. hepaticus, and other Helicobacter spp. was examined using bacterial culture, PCR-based detection, and serological tests. RESULTS: Culture of Helicobacter spp. from biliary brush samples was unsuccessful. Approximately 13.0% (15/115) of the bile samples collected from patients with a variety of gastrointestinal cancers, including pancreatic and biliary tract cancers, tested positive for one of the enterohepatic non-H. pylori helicobacter species as determined by PCR. Specifically, H. bilis and H. hepaticus DNA were detected in 11 and 4 bile samples, respectively. Approximately 20%-40% of the patients tested positive for serum non-H. pylori helicobacter IgG antibodies. The seroprevalence of H. bilis and H. hepaticus in the patients without evidence of H. pylori infection appeared to be higher in the pancreatic cancer group than in the control group. CONCLUSION: Our findings suggest a role for Helicobacter spp., especially H. bilis and H. hepaticus, in the etiology of pancreatic and biliary tract cancers.

Smart Gene™ as an effective non-invasive point-of-care test to detect Helicobacter pylori clarithromycin-resistant mutation.

BACKGROUND AND AIM: Smart Gene™ was developed based on the concept of point-of-care genetic testing. We evaluated the detection performance of a reagent for Helicobacter pylori (H. pylori) clarithromycin (CAM)-resistant mutation assessment and determined the association between the results of Smart Gene™ and those of eradication therapy for H. pylori. METHODS: In 2020, the present study was conducted on participants of the H. pylori test and treat project in Saga Prefecture. The submitted stool samples were measured for H. pylori gene and CAM-resistant mutation by Smart Gene™, and the results were compared with real-time polymerase chain reaction (PCR) and sequencing analysis. Finally, the results of the eradication therapy were examined for each result of Smart Gene™. RESULTS: Stool samples were obtained from 139 patients who were tested positive by stool antigen test and were analyzed. The H. pylori detection rate was 95.7% by Smart Gene™, 92.8% by real-time PCR (P < 0.01), and 89.2% by sequencing analysis (P = 0.06). The overall concordance rate for CAM-resistant mutation between Smart Gene™ and sequencing analysis was 96.7%. Moreover, 35 of 48 students with CAM-resistant mutation and 33 of the 35 students with a mutation without CAM resistance succeeded in CAM-containing triple therapy, and the success rate was significantly higher for the mutation without CAM resistance (P = 0.012). CONCLUSIONS: The detection performance of Smart Gene™ was comparable with that of real-time PCR and sequencing analysis. It is expected that the success rate of eradication would be further improved by using the reagent.

Gastrointestinal adverse reactions reduce the success rate of Helicobacter pylori eradication therapy: A multicenter prospective cohort study.

BACKGROUND: The screening and treatment of Helicobacter pylori infection for all junior high students in Saga Prefecture, Japan, were started in 2016. The present study aims to evaluate the influence of adverse reactions on the success of the eradication therapy. METHODS: From 2017 to 2019, 25,006 third-grade junior high school students were tested for urinary anti-H. pylori antibodies. Positive cases were confirmed by H. pylori stool antigen tests. Of the 531 students who were found to be H. pylori-positive, 390 (358 in first-line and 32 in second-line therapy) underwent eradication therapy, and 274 (242 in first-line and 32 in second-line) students actually completed a self-reported form to rate stool consistency (based on the Bristol Stool Scale), the maximum number of bowel movements, and abdominal symptoms during the 7 days of treatment. RESULTS: Among the 274 students, the total of primary and secondary eradication success rates was 87% (95% confidential interval: 82.9-90.1) in intention-to-treat analysis. On days 4, 5, and 6, stool consistency was looser in the primary eradication failure group than in the success group (p < .05). Looser stool consistencies were observed in male students with abdominal pain compared to those who did not experience pain (p < .05). Abdominal pain and diarrhea were detected in 28.5% and 42.7% of the subjects, respectively. The overall incidence of other adverse events was low (n = 8/274, 2.9%), and only two students discontinued treatment because of adverse events. CONCLUSIONS: Softening of the stool was related to the eradication failure in the junior high school students, especially in males with abdominal pain. Adverse effects did not induce discontinuation of the eradication treatment.

A nationwide questionnaire survey on accidental magnet ingestion in children in Japan.

AIM: The aim is to investigate the actual situation of accidental ingestion of magnets in children in Japan and the clinical features of the resulting gastrointestinal damage. METHODS: We developed a questionnaire and sent it to 496 board-certified training hospitals nationwide. Information was collected on the number of children with accidental magnet intake from 2015 to 2017, witnesses of magnet intake, number and type of magnets, presence or absence of gastrointestinal injury, treatment, etc RESULTS: The number of cases of accidental ingestion of magnets within the study period was 104, with a median age of 2 years. About half of the incidents were unwitnessed. There were 33 cases of accidental ingestion of multiple magnets. Among them, oesophagogastroduodenoscopy was performed in 4 children and surgery in 10, and significantly invasive treatment was required in comparison with single-magnet ingestion. Gastrointestinal injury was observed in 11 cases, 10 of which were caused by multiple-magnet ingestion. All 10 of these patients underwent surgical treatment. There was no mortality. CONCLUSION: The incidence of accidental magnet ingestion in Japan is estimated to be 50-70 per year. Unwitnessed cases are not uncommon. Multiple magnet ingestion often causes gastrointestinal injury. Many cases of gastrointestinal injury are caused by ingestion of magnetic toys.

An approach to exploring associations between hospital structural measures and patient satisfaction by distance-based analysis.

BACKGROUND: Patient satisfaction studies have explored domains of patient satisfaction, the determinants of domains, and score differences of domains by patient/hospital structural measures but reports on the structure of patient satisfaction with respect to similarities among domains are scarce. This study is to explore by distance-based analysis whether similarities among patient-satisfaction domains are influenced by hospital structural measures, and to design a model evaluating relationships between the structure of patient satisfaction and hospital structural measures. METHODS: The Hospital Consumer Assessment of Healthcare Providers and Systems 2012 survey scores and their structural measures from the Hospital Compare website reported adjusted percentages of scale for each hospital. Contingency tables of nine measures and their ratings were designed based on hospital structural measures, followed by three different distance-based analyses - clustering, correspondence analysis, and ordinal multidimensional scaling - for robustness to identify homogenous groups with respect to similarities. RESULTS: Of 4,677 hospitals, 3,711 (79.3%) met the inclusion criteria and were analyzed. The measures were divided into three groups plus cleanliness. Certain combinations of these groups were shown to be dependent on hospital structural measures. High value ratings for communication and low value ratings for medication explanation, quietness and staff responsiveness were not influenced by hospital structural measures, but the varied-ratings domain group similarities, including items such as global evaluation and pain management, were affected by hospital structural measures. CONCLUSIONS: Distance-based analysis can reveal the hidden structure of patient satisfaction. This study suggests that hospital structural measures including hospital size, the ability to provide acute surgical treatment, and hospital interest in improving medical care quality are factors which may influence the structure of patient satisfaction.

Association between house renovation during pregnancy and wheezing in the first year of life: The Japan environment and children's study.

BACKGROUND: Wheezing is a common symptom in infants, which may occasionally develop into asthma. There are many factors related to infant wheezing, including anatomical features, viral infections, and passive smoking. There are only a few reports on the association between renovation and pregnancy worldwide, and reports on this association are inadequate in Japan. This study aimed to examine the association between house renovation and new construction during pregnancy and wheezing in infants during the first year of life using data from the Japan Environment and Children's Study (JECS). METHODS: Data of pregnant women registered in JECS were collected using self-administered questionnaires during the second/third trimester and 1 month after delivery. Childbirth records were completed by the doctors. Similarly, wheezing in infants was evaluated using self-administered questionnaires 1 year after birth. Logistic regression analysis was used to determine the primary outcome. RESULTS: In total, 75,731 infants, excluding those with unknown gender, who were not singleton infants, and who relocated during pregnancy and the first month of life, were examined in this study. Renovation during pregnancy increased the prevalence of wheezing (odds ratio [OR]: 1.33, 95% confidence interval [CI]: 1.20-1.48) and recurrent wheezing (OR: 1.22, 95% CI: 1.00-1.48) in the first year of life. The relationship between new construction during pregnancy and wheezing in infants was insignificant (OR: 0.98, 95% CI: 0.90-1.06). CONCLUSIONS: Renovation during pregnancy may be a risk factor for wheezing in infants, and should be avoided.

Effect of probiotics during vonoprazan-containing triple therapy on gut microbiota in Helicobacter pylori infection: A randomized controlled trial.

BACKGROUND: Probiotics are beneficial to patients with Helicobacter pylori infections by modulating the gut microbiota. Biofermin-R (BFR) is a multiple antibiotic-resistant lactic acid bacteria preparation of Enterococcus faecium 129 BIO 3B-R and is effective in normalizing the gut microbiota when used in combination with antibiotics. This study aimed to determine the effect of BFR in combination with vonoprazan (VPZ)-based therapy on gut microbiota. METHODS: Patients with positive urinary anti-H pylori antibody test (primary test) and fecal H pylori antigen test (secondary test) were examined. Patients in group 1 (BFR- ) received VPZ (20 mg twice daily), amoxicillin (750 mg twice daily), and clarithromycin (400 mg twice daily) for 7 days. Patients in group 2 (BFR+ ) received BFR (3 tablets/day) for 7 days, in addition to the aforementioned treatments. Following treatment, the relative abundance, α-diversity, and ß-diversity of gut microbiota were assessed. RESULTS: Supplementation with BFR prevented the decrease in a-diversity after eradication therapy (Day 7). ß-diversity was similar between groups. The incidence rate of diarrhea was non-significantly higher in the BFR- than in the BFR+ group (73.1% vs 56.5%; P = .361). Stool consistency was comparable in the BFR+ group on Days 7 and 1 (3.86 ± 0.95 vs 3.86 ± 1.46; P = .415). CONCLUSION: Biofermin-R combined with VPZ-based therapy resulted in higher microbial α-strain diversity and suppressed stool softening during H pylori eradication therapy.

Assessment of a novel method to detect clarithromycin-resistant Helicobacter pylori using a stool antigen test reagent.

BACKGROUND: The resistance rate of Helicobacter pylori to clarithromycin (CAM) is high among infected children in Japan. Therefore, a new method for detecting CAM-resistant H. pylori using a minimally invasive technique is strongly desired. We aimed to investigate the clinical usefulness of our newly developed nested polymerase chain reaction-quenching probe (Nested PCR-QP) method using stool specimens. METHODS: We first evaluated our method using a residual solution of the H. pylori stool antigen test for adolescents. Then, we evaluated our method using culture testing for adults. RESULTS: Among 57 middle school students with H. pylori, the Nested PCR-QP test results of 53 (90.3%) were able to be analyzed. A total of 28 students had CAM resistance mutations. We found a genetic mutation in 28 students and no mutation in 23 students, and these results were consistent with those of PCR-direct sequencing. In the 23 adults who were diagnosed with H. pylori infection using the rapid urease test and culture testing, we were able to use Nested PCR-QP for analyzing 21 adults who tested positive in the stool H. pylori antigen test. The results obtained for all 21 adults were consistent with those obtained via the drug susceptibility test. CONCLUSIONS: Our novel method could be useful for non-invasively detecting CAM resistance mutations in H. pylori. This may help select a drug to reduce eradication failure rates against H. pylori. Trial registration This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (no. UMIN000030632, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034977 ) on 29 December 2017.

Serum Pepsinogen Values in Japanese Junior High School Students With Reference to Helicobacter Pylori Infection.

BACKGROUND: Distributions of serum pepsinogen (PG) values were assessed in Helicobacter pylori-infected and non-infected junior high school students (aged 12-15 years) in Japan. METHODS: All junior high school students (1,225 in total) in Sasayama city, who were basically healthy, were asked to provide urine and serum samples, which were used to measure urine and serum H. pylori antibodies using ELISA kits and PG values. The subjects, whose urine and serum antibodies were both positive, were considered H. pylori infected. RESULTS: Of the 187 subjects who provided urine and blood samples, 8 were infected, 4 had discrepant results, 4 had negative serum antibody titers no less than 3.0 U/ml, and 171 were non-infected. In the H. pylori non-infected subjects, the median PG I and PG II values and PG I to PG II ratio (PG I/II) were 40.8 ng/mL, 9.5 ng/mL, and 4.4, respectively, whereas in the infected subjects, these values were 55.4 ng/mL, 17.0 ng/mL, and 3.3, respectively (each P < 0.01). In the non-infected subjects, PG I and PG II were significantly higher in males than in females (P < 0.01). CONCLUSIONS: The PG I and PG II values were higher, and the PG I/II was lower in H. pylori infected students than in non-infected students. In H. pylori non-infected students, males showed higher PG I and PG II values than females. The distributions of PG values in junior high school students differed from those in adults.

Evaluation of a Novel Stool Antigen Rapid Test Kit for Detection of Helicobacter pylori Infection.

The Quick Chaser H. pylori (QCP), which is a novel antigen detection kit for Helicobacter pylori, was developed recently. The previous examination kits targeted the catalase of H. pylori; however, this new test kit, to the best of our knowledge, is the first kit to target the flagellar protein of H. pylori The present study aimed to evaluate the efficacy of QCP compared with that of the already commercially available rapid test kit Testmate Rapid Pylori Antigen (TRP). TRP and QCP were utilized in 71 participants. The positive and negative concordance ratios of QCP to TRP were 100% (57/57) and 92.9% (13/14), respectively. Sensitivity based on the rapid urease test and culture test was 92.3%. Results of the dilution sensitivity test showed that QCP was eight times more sensitive to an H. pylori standard strain and the clarithromycin (CAM)-resistant clinical isolate and four times more sensitive to a CAM-susceptible clinical isolate than TRP. For the cross-reactivity test, 27 strains that exist in human feces, such as the Helicobacter genus, Bifidobacterium genus, Lactobacillus genus, and other resident bacteria, were selected. The results obtained using QCP were all negative, and no cross-reaction was observed. In conclusion, compared with TRP, QCP can detect H. pylori using clinical specimens with high sensitivity, regardless of CAM susceptibility and tolerance. No cross-reactivity was observed with other intestinal bacteria in humans. The kit is considered extremely useful in clinical settings.

Metronidazole for Helicobacter pylori eradication therapy among children and adolescents in Japan: Overcoming controversies and concerns.

BACKGROUND: Metronidazole is an antiprotozoal drug used to treat a broad spectrum of infectious diseases, including Helicobacter pylori (H pylori) infections. In Japan, metronidazole is approved for the eradication therapy of H pylori as a second-line regimen among adults, but it has not yet been approved for use among children and adolescents. MATERIALS AND METHODS: To perform this narrative review, we searched the relevant literature on important events in the history of the use of metronidazole, its mechanisms of action, its efficacy, and the adverse effects reported in clinical trials or cohort studies in Japan. RESULTS: At present, metronidazole resistance has not been a serious issue in Japan in large part due to its restricted use. Emerging evidence from randomized controlled trials demonstrates higher eradication rates for metronidazole than for clarithromycin, supporting its use in both first-line and second-line eradication therapies. Among the reported adverse effects, there has been lingering concern over the potential carcinogenicity of metronidazole in humans. However, the possibility of an increased cancer risk is not limited to metronidazole; the long-term use of antibiotics has been linked to increased risk for some site-specific cancers. However, recent prospective studies have suggested that short-term exposure to antibiotics is not associated with an increased cancer risk. CONCLUSION: Sensible use of metronidazole backed by research evidence could maximize the benefits associated with H pylori eradication in Japan.

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.

Rapidly decreasing prevalence of Helicobacter pylori among Japanese children and adolescents.

BACKGROUND: The secular trend in the prevalence of Helicobacter pylori (H. pylori) infection among children and adolescents in Japan has not been well documented. MATERIALS AND METHODS: We reviewed all relevant literature published between 1991 and 2017, focusing on the relationship between the prevalence of H. pylori infection and birth year. Our literature search covered all journal articles, conference proceedings and meeting abstracts that reported the prevalence of H. pylori infection in Japanese subjects under 20 years of age. RESULTS: We examined the prevalence of H. pylori infection according to birth year on the basis of data points, which comprised 20,269 subjects of 81 groups. Three-coefficient logistic regression analysis was performed to examine the trend in H. pylori prevalence. The prevalence was approximately 10% in the individuals born in 1985, but it decreased to 3% in the individuals born in 2011. The plot of H. pylori prevalence against birth year clearly indicated a birth-cohort effect: the earlier the birth year, the higher the prevalence. CONCLUSIONS: Our analysis revealed a rapidly decreasing prevalence of H. pylori infection among Japanese children and adolescents over the past three decades.

Helicobacter pylori Infection in Children and Adolescents.

About one-third of all children worldwide is infected with H. pylori and its prevalence is low in developed and high in developing countries. H. pylori is mainly acquired during childhood and transmission of the bacterium commonly proceeds from person to person, especially among family members. The most frequent transmission route is from the mother to children. Various gastrointestinal and extra-gastrointestinal diseases are reported to be associated with H. pylori in children and adolescents, but the strongest recommendation for testing and treating is introduced only with children and adolescents having peptic ulcer disease. Iron deficiency anemia and chronic immune thrombocytopenic purpura are also considered for testing and treating, but the effectiveness is somewhat controversial. Invasive diagnosis is recommended, whereas none of the available diagnostic tests have 100% accuracy for reliable diagnosis, and therefore at least two or more tests should be performed. Urea breath test is the most reliable among the non-invasive tests. Because the number of antibiotics-resistant H. pylori strains is increasing, it is desirable to conduct a drug susceptibility test before treatment and to select the corresponding regime. H. pylori has been proven to be a major cause of gastric cancer and 'screen-and-treat' strategies are recommended in communities at high risk of gastric cancer. However, the application to children and adolescents is controversial. An effective vaccine is desirable, but not yet available. Screen-and-treat for adolescents has started in a few areas in Japan, where conditions are well established. New prevention strategies for gastric cancer are awaited worldwide.

Gastric cancer in children and adolescents in Japan.

BACKGROUND: Very limited data are available on childhood gastric cancer. Using a retrospective survey and literature review, we assessed the clinical features of gastric cancer in children and adolescents. METHODS: We collected information on childhood gastric cancer from pediatricians of 518 hospitals that issue the title of "certified board pediatrician" approved by Japan Pediatric Society, using a questionnaire on background, diagnosis year, onset symptoms, tumor location, histology, nodular gastritis, Helicobacter pylori testing, treatment, and prognosis. Studies were collected using PubMed and the NPO Japan Medical Abstracts Society database. Data for childhood gastric cancer were abstracted from the Japanese Vital Statistics database. RESULTS: Of the 518 hospitals, 349 returned the questionnaire, which identified four patients. Literature review identified 77 cases of gastric cancer, and we analyzed data for 80 children <16 years old. Most patients were >10 years old, and there were no sex differences. Onset symptoms ranged from abdominal pain to non-localized. Sixteen of 44 children had a family history of cancer; 10 had a family history of gastric cancer. Histologically, approximately 80% had undifferentiated-type carcinoma. Prognosis was extremely poor, and two of three tested children were positive for H. pylori infection. Childhood gastric cancer death has been declining. CONCLUSIONS: Childhood gastric cancer is rare in Japan, and information on H. pylori in childhood gastric cancer patients is limited. Declining childhood gastric cancer rates may reflect the decreasing prevalence of infection but further study is necessary to clarify the relationship between H. pylori and gastric cancer.

Randomized controlled trial: PPI-based triple therapy containing metronidazole versus clarithromycin as first-line treatment for Helicobacter pylori in adolescents and young adults in Japan.

BACKGROUND/AIMS: Treating Helicobacter pylori infection in young people is effective for preventing gastric cancer. This study compares the efficacy of triple therapies in adolescents and young adults in Japan. METHODS: This multicenter, randomized trial was conducted between February 2012 and March 2015. Infected participants were stratified into adolescents (13-19 years) and young adults (20-39 years). They were randomly assigned to a clarithromycin based (PAC) or metronidazole based (PAM) triple therapy for 1 week. RESULTS: Overall, 137 and 169 participants received the PAC and PAM treatments, respectively. In adolescents, the H. pylori eradication rates were 60.5% and 63.4% for PAC, and 98.3% and 100% for PAM in the intention-to-treat (ITT) and per-protocol (PP) analyses, respectively. In young adults, the eradication rates were 67.0% and 66.7% for PAC, and 95.5% and 96.3% for PAM in ITT and PP analyses, respectively. The eradication rate of PAM was significantly higher than that of PAC in both strata. No severe adverse events were observed. CONCLUSION: In Japan, PAM may be selected as a first-line treatment for young people with H. pylori if antibiotic susceptibility tests cannot be performed.

Diagnostic accuracy of urine Helicobacter pylori antibody test in junior and senior high school students in Japan.

BACKGROUND: To prevent gastric cancer, a Helicobacter pylori test-and-treat strategy has been proposed. In Japan, routine urine examinations are performed to screen for kidney diseases; it is therefore convenient to screen for H. pylori infection via urine antibody (u-Ab) testing. AIM: To evaluate the diagnostic accuracy of u-Ab testing in students using 13 C-urea breath testing (UBT) as a standard. METHODS: The study population included 806 junior or senior high school students in Japan who provided urine samples and/or underwent UBT. Students with a positive u-Ab test or discrepant results between the u-Ab test and UBT were asked to provide additional stool and/or blood samples or to repeat the UBT. Urinary protein was detected using a urine test strip. RESULTS: The positive rates for the u-Ab test and UBT were 8.9% (71/795) and 5.5% (44/801), respectively. The u-Ab test showed 88.4% sensitivity and 95.7% specificity using UBT as a standard. In the final diagnoses, the u-Ab test showed 97.6% sensitivity, 96.5% specificity, 61.2% positive predictive value (PPV), and 99.9% negative predictive value (NPV). Of the 508 samples tested using a urine test strip, negative results were obtained for 450 subjects with a sensitivity of 90%, specificity of 97.9%, PPV of 66.7%, and NPV of 99.5%. Proteinuria was detected in 58 samples, with a sensitivity of 100%, specificity of 88.9%, PPV of 40%, and NPV of 100%. CONCLUSIONS: The u-Ab test is highly accurate and suitable for detecting H. pylori infection. However, the occurrence of proteinuria may yield false-positive results.