Masao Kobayakawa

Randomized clinical trial: rikkunshito in the treatment of functional dyspepsia—a multicenter, double-blind, randomized, placebo-controlled study

Rikkunshito, a standardized Japanese herbal medicine, is thought to accelerate gastric emptying and relieve dyspepsia, although no large‐scale, randomized, placebo‐controlled trials of rikkunshito have been conducted. This study aimed to determine the efficacy and safety of rikkunshito for treating functional dyspepsia (FD).

Tegafur/gimeracil/oteracil (S-1) approved for the treatment of advanced gastric cancer in adults when given in combination with cisplatin: a review comparing it with other fluoropyrimidine-based therapies

S-1 is a combination of three pharmacological compounds, namely tegafur, gimeracil, and oteracil potassium. Tegafur is a prodrug of 5-fluorouracil (5-FU), an oral fluoropyrimidine, and it has been developed as a replacement for infusional 5-FU therapy. S-1-based chemotherapy and the combination of S-1 and cisplatin are the most reasonable first-line standards for unresectable advanced gastric cancer in Japan. However, the application of S-1 for gastric cancer has been delayed in Western countries. One reason for this delay is that the pharmacokinetics of tegafur is affected by polymorphisms in cytochrome P-450 2A6, and consequently 5-FU concentrations in the plasma are more likely to be elevated in patients from Western countries. Although the dose of S-1 was reduced compared with the approved dose in Japan, a global Phase III study reported similar results regarding overall survival between S-1 plus cisplatin and infusional 5-FU plus cisplatin arms. Significant safety advantages were observed in the S-1 plus cisplatin arm compared with the infusional 5-FU plus cisplatin arm. S-1 plus cisplatin has become acceptable for Western countries, also, as a choice for unresectable advanced gastric cancer. Comparisons with capecitabine and combination of several targeting agents with S-1 are expected in the future.

Predictive findings for Helicobacter pylori-uninfected, -infected and -eradicated gastric mucosa: Validation study

AIM To validate the usefulness of screening endoscopy findings for predicting Helicobacter pylori (H. pylori) infection status. METHODS H. pylori infection status was determined by histology, serology, and the urea breast test in 77 consecutive patients who underwent upper endoscopy. Based on the findings, patients were categorized as H. pylori-uninfected, -infected, or -eradicated cases. Using six photos of certain sites in the stomach per case, we determined the presence or absence of the following endoscopic findings: regular arrangement of collecting venules (RAC), linear erythema, hemorrhage, fundic gland polyp (FGP), atrophic change, rugal hyperplasia, edema, spotty erythema, exudate, xanthoma, and mottled patchy erythema (MPE). The diagnostic odds ratio (DOR) and inter-observer agreement (Kappa value) for these 11 endoscopic findings used in the determination of H. pylori infection status were calculated. RESULTS Of the 77 patients [32 men and 45 women; mean age (SD), 39.7 (13.4) years] assessed, 28 were H. pylori uninfected, 28 were infected, and 21 were eradicated. DOR values were significantly high (< 0.05) for the following H. pylori cases: uninfected cases with RAC (11.5), linear erythema (24.5), hemorrhage (4.1), and FGP (34.5); for infected cases with atrophic change (8.67), rugal hyperplasia (15.8), edema (14.2), spotty erythema (11.5), and exudate (3.52); and for eradicated cases with atrophic change (32.4) and MPE (103.0). Kappa values were excellent for FGP (0.93), good for RAC (0.63), hemorrhage (0.79), atrophic change (0.74), and MPE (0.75), moderate for linear erythema (0.51), rugal hyperplasia (0.49), edema (0.58), spotty erythema (0.47), and exudate (0.46), and poor for xanthoma (0.19). CONCLUSION The endoscopic findings of RAC, hemorrhage, FGP, atrophic change, and MPE will be useful for predicting H. pylori infection status.

Accuracy of endoscopic diagnosis of Helicobacter pylori infection according to level of endoscopic experience and the effect of training

BackgroundAccurate prediction of Helicobacter pylori infection status on endoscopic images can contribute to early detection of gastric cancer, especially in Asia. We identified the diagnostic yield of endoscopy for H. pylori infection at various endoscopist career levels and the effect of two years of training on diagnostic yield.MethodsA total of 77 consecutive patients who underwent endoscopy were analyzed. H. pylori infection status was determined by histology, serology, and the urea breast test and categorized as H. pylori-uninfected, -infected, or -eradicated. Distinctive endoscopic findings were judged by six physicians at different career levels: beginner (<500 endoscopies), intermediate (1500–5000), and advanced (>5000). Diagnostic yield and inter- and intra-observer agreement on H. pylori infection status were evaluated. Values were compared between the two beginners after two years of training. The kappa (K) statistic was used to calculate agreement.ResultsFor all physicians, the diagnostic yield was 88.9% for H. pylori-uninfected, 62.1% for H. pylori-infected, and 55.8% for H. pylori-eradicated. Intra-observer agreement for H. pylori infection status was good (K > 0.6) for all physicians, while inter-observer agreement was lower (K = 0.46) for beginners than for intermediate and advanced (K > 0.6). For all physicians, good inter-observer agreement in endoscopic findings was seen for atrophic change (K = 0.69), regular arrangement of collecting venules (K = 0.63), and hemorrhage (K = 0.62). For beginners, the diagnostic yield of H. pylori-infected/eradicated status and inter-observer agreement of endoscopic findings were improved after two years of training.ConclusionsThe diagnostic yield of endoscopic diagnosis was high for H. pylori-uninfected cases, but was low for H. pylori-eradicated cases. In beginners, daily training on endoscopic findings improved the low diagnostic yield.

Association of baseline plasma des-acyl ghrelin level with the response to rikkunshito in patients with functional dyspepsia

We recently conducted a randomized placebo‐controlled trial on the efficacy and safety of rikkunshito, a standardized Japanese herbal medicine, for the treatment of functional dyspepsia (FD). The present post‐hoc study aimed to evaluate the differences in clinical characteristics between responders and non‐responders among FD patients who received rikkunshito for 8 weeks.

Association of visceral fat area, smoking, and alcohol consumption with reflux esophagitis and Barrett's esophagus in Japan

Background Central obesity has been suggested as a risk factor for gastroesophageal reflux disease. The aim of this study was to evaluate the association of visceral fat area and other lifestyle factors with reflux esophagitis or Barrett’s esophagus in Japanese population. Methods Individuals who received thorough medical examinations including the measurement of visceral fat area by abdominal computed tomography were enrolled. Factors associated with the presence of reflux esophagitis, the severity of reflux esophagitis, or the presence of Barrett’s esophagus were determined using multivariable logistic regression models. Results A total of 2608 individuals were eligible for the analyses. Visceral fat area was associated with the presence of reflux esophagitis both in men (odds ratio, 1.21 per 50 cm2; 95% confident interval, 1.01 to 1.46) and women (odds ratio, 2.31 per 50 cm2; 95% confident interval, 1.57 to 3.40). Current smoking and serum levels of triglyceride were also associated with the presence of reflux esophagitis in men. However, significant association between visceral fat area and the severity of reflux esophagitis or the presence of Barrett’s esophagus was not shown. In men, excessive alcohol consumption on a drinking day, but not the frequency of alcohol drinking, was associated with both the severity of reflux esophagitis (odds ratio, 2.13; 95% confident interval, 1.03 to 4.41) and the presence of Barrett’s esophagus (odds ratio, 1.71; 95% confident interval, 1.14 to 2.56). Conclusion Visceral fat area was independently associated with the presence of reflux esophagitis, but not with the presence of Barrett’s esophagus. On the other hand, quantity of alcohol consumption could play a role in the development of severe reflux esophagitis and Barrett’s esophagus in Japanese population.

Long-Term Trends in Esophageal Candidiasis Prevalence and Associated Risk Factors with or without HIV Infection: Lessons from an Endoscopic Study of 80,219 Patients.

Background The prevalence of candida esophagitis (CE) might be changing in an era of highly active antiretroviral therapy (HAART) among HIV-infected patients or today’s rapidly aging society among non-HIV-infected patients. However, few studies have investigated long-term CE trends, and CE risk factors have not been studied in a large sample, case-control study. This study aimed to determine long-term trends in CE prevalence and associated risk factors for patients with or without HIV infection. Methods Trends in CE prevalence were explored in a cohort of 80,219 patients who underwent endoscopy between 2002 and 2014. Risks for CE were examined among a subcohort of 6,011 patients. In risk analysis, we assessed lifestyles, infections, co-morbidities, immunosuppressants, and proton-pump inhibitors (PPIs). All patients were tested for HIV, hepatitis B or C virus, and syphilis infection. For HIV-infected patients, sexual behavior, CD4 cell count, history of HAART were also assessed. Results CE prevalence was 1.7% (1,375/80,219) in all patients, 9.8% (156/1,595) in HIV-infected patients, and 1.6% (1,219/78,624) in non-HIV-infected patients. CE prevalence from 2002-2003 to 2012-2014 tended to increase in non-HIV-infected patients (0.6% to 2.5%; P<0.01) and decrease in HIV-infected patients (13.6% to 9.0%; P=0.097). Multivariate analysis revealed increasing age (odds ratio [OR], 1.02; p=0.007), HIV infection (OR, 4.92; p<0.001), and corticosteroid use (OR, 5.90; p<0.001) were significantly associated with CE, and smoking (OR, 1.32; p=0.085) and acetaminophen use (OR, 1.70; p=0.097) were marginally associated. No significant association was found with alcohol consumption, hepatitis B or C virus, syphilis, diabetes mellitus, cardiovascular disease, cerebrovascular disease, chronic kidney disease, liver cirrhosis, anticancer, or PPIs use. In HIV-infected patients, CD4 cell count <100/μL (OR, 4.83; p<0.001) and prior HAART (OR, 0.35; p=0.006) were independently associated with CE, but sexual behavior was not. Among corticosteroid users, CE was significantly associated with higher prednisone-equivalent dose (p=0.043 for trend test). Conclusions This large, endoscopy-based study demonstrated that CE prevalence increased in non-HIV-infected patients but decreased in HIV-infected patients over 13 years. Risk analysis revealed that increasing age, HIV infection, and corticosteroids use, particularly at higher doses, were independently associated with CE, but alcohol, other infections, diabetes, anticancer drugs, and PPIs use were not.

Histological features of nodular gastritis and its endoscopic classification

OBJECTIVES:  To clarify the histological features and endoscopic classifications of nodular gastritis (NG).

Short-Term Safety and Efficacy of Balloon-Occluded Retrograde Transvenous Obliteration Using Ethanolamine Oleate: Results of a Prospective, Multicenter, Single-Arm Trial

PURPOSE To evaluate 90-day outcomes after balloon-occluded retrograde transvenous obliteration (BRTO) with ethanolamine oleate (EO) in patients with gastric varices (GVs). MATERIALS AND METHODS An 8-site prospective single-arm clinical trial was conducted. Patients who had endoscopically confirmed GVs with a gastrorenal shunt were eligible for the study. Overnight BRTO was performed, and efficacy was evaluated by endoscopy and contrast-enhanced computed tomography (CT). RESULTS Forty-five patients (26 men and 19 women; mean age, 67.8 y) were enrolled. The complete regression rate of GVs based on endoscopic images on day 90 was 79.5% (35 of 44 patients; 95% confidence interval, 64.7%-90.2%). The rate of complete thrombosis of GVs based on contrast-enhanced CT on day 90 was 93.0% (40 of 43 patients; 95% confidence interval, 80.9%-98.5%). One patient experienced 2 events of bleeding from GVs, which was different from the GVs treated with BRTO. Appearance of new esophageal varices (EVs) or worsening of existing EVs occurred in 16 of 45 patients (35.6%). Forty-four of 45 patients (97.8%) experienced adverse events (AEs) related to EO, which included fever in 24 (53.3%), hematuria in 23 (51.1%), hemolysis in 16 (35.6%), back pain in 16 (35.6%), and abdominal pain in 10 (22.2%). One case of moderate to severe ascites (2.3%) was observed on day 90. One case of sepsis was the only serious AE observed in relation to EO. CONCLUSIONS The present study demonstrates that BRTO with EO for the treatment of GVs is a clinically effective procedure with many mild to moderate AEs.

Impact of rapid identification of positive blood cultures using the Verigene system on antibiotic prescriptions: A prospective study of community-onset bacteremia in a tertiary hospital in Japan

Background Rapid identification of positive blood cultures is important for initiation of optimal treatment in septic patients. Effects of automated, microarray-based rapid identification systems on antibiotic prescription against community-onset bacteremia (COB) remain unclear. Methods We prospectively enrolled 177 patients with 185 COB episodes (occurring within 72 h of admission) over 17 months. Bacteremia episodes due to gram-positive bacteria (GP) and gram-negative bacteria (GN) in the same patient were counted separately. For GP bacteremia, patients with ≥2 sets of positive blood cultures were included. The primary study objective was evaluating the rates of antibiotic prescription changes within 2 days of rapid identification using the Verigene system. Results Bacteremia due to GN and GP included 144/185 (77.8%) and 41/185 (22.2%) episodes, respectively. Antibiotic prescription changes occurred in 51/185 cases (27.6% [95%CI:21.3–34.6%]) after Verigene analysis and 70/185 cases (37.8% [30.8–45.2%]) after conventional identification and susceptibility testing. Prescription changes after Verigene identification were more frequent in GP (17/41[41.5%]) than in GN (34/144[23.5%]). Among bacteremia due to single pathogen targeted by Verigene test, bacterial identification agreement between the two tests was high (GP: 38/39[97.4%], GN: 116/116[100%]). The Verigene test correctly predicted targeted antimicrobial resistance. The durations between the initiation of incubation and reporting of the results for the Verigene system and conventional test was 28.3 h (IQR: 25.8–43.4 h) and 90.6 h (68.3–118.4 h), respectively. In only four of the seven episodes of COB in which two isolates were identified by conventional tests, the Verigene test correctly identified both organisms. Conclusion We observed a high rate of antibiotic prescription changes after the Verigene test in a population with COB especially in GP. The Verigene test would be a useful tool in antimicrobial stewardship programs among patients with COB.