Evidence-based clinical practice guidelines for gastroesophageal reflux disease 2015.

As an increase in gastroesophageal reflux disease (GERD) has been reported in Japan, and public interest in GERD has been increasing, the Japanese Society of Gastroenterology published the Evidence-based Clinical Practice Guidelines for GERD (1st edition) in 2009. Six years have passed since its publication, and there have been a large number of reports in Japan concerning the epidemiology, pathophysiology, treatment, and Barrett's esophagus during this period. By incorporating the contents of these reports, the guidelines were completely revised, and a new edition was published in October 2015. The revised edition consists of eight items: epidemiology, pathophysiology, diagnosis, internal treatment, surgical treatment, esophagitis after surgery of the upper gastrointestinal tract, extraesophageal symptoms, and Barrett's esophagus. This paper summarizes these guidelines, particularly the parts related to the treatment for GERD. In the present revision, aggressive proton pump inhibitor (PPI) maintenance therapy is recommended for severe erosive GERD, and on-demand therapy or continuous maintenance therapy is recommended for mild erosive GERD or PPI-responsive non-erosive GERD. Moreover, PPI-resistant GERD (insufficient symptomatic improvement and/or esophageal mucosal break persisting despite the administration of PPI at a standard dose for 8 weeks) is defined, and a standard-dose PPI twice a day, change in PPI, change in the PPI timing of dosing, addition of a prokinetic drug, addition of rikkunshito (traditional Japanese herbal medicine), and addition of histamine H2-receptor antagonist are recommended for its treatment. If no improvement is observed even after these treatments, pathophysiological evaluation with esophageal impedance-pH monitoring or esophageal manometry at an expert facility for diseases of the esophagus is recommended.

Evidence-based clinical practice guidelines for functional dyspepsia.

General interest in functional gastrointestinal disorders is increasing among Japanese doctors as well as patients. This increase can be attributed to a number of factors, including recent increased interest in quality of life and advances in our understanding of the pathophysiology of gastrointestinal disease. Japan recently became the world's first country to list "functional dyspepsia" as a disease name for national insurance billing purposes. However, recognition and understanding of functional dyspepsia (FD) remain poor, and no standard treatment strategy has yet been established. Accordingly, the Japanese Society of Gastroenterology (JSGE) developed an evidence-based clinical practice guideline for FD, consisting of five sections: concept, definition, and epidemiology; pathophysiology; diagnosis; treatment; and prognosis and complications. This article summarizes the Japanese guideline, with particular focus on the treatment section. Once a patient is diagnosed with FD, the doctor should carefully explain the pathophysiology and benign nature of this condition, establish a good doctor-patient relationship, and then provide advice for daily living (diet and lifestyle modifications, explanations, and reassurance). The proposed pharmacological treatment is divided into two steps: initial treatment including an acid inhibitory drug (H2RA or PPI) or prokinetics, (strong recommendation); second-line treatment including anxiolytics, antidepressants, and Japanese traditional medicine (weak recommendation). H. pylori eradication, strongly recommended with a high evidence level, is positioned separately from other treatment flows. Conditions that do not respond to these treatment regimens are regarded as refractory FD. Patients will be further examined for other organic disorders or will be referred to specialists using other approaches such as psychosomatic treatment.

Multinational, double-blind, randomised, placebo-controlled, prospective study of esomeprazole in the prevention of recurrent peptic ulcer in low-dose acetylsalicylic acid users: the LAVENDER study.

OBJECTIVES: To evaluate if esomeprazole prevents recurrent peptic ulcer in adult patients with a history of peptic ulcer receiving low-dose acetylsalicylic acid (ASA, aspirin) for cardiovascular protection in East Asia. METHODS: In this prospective, randomised, double-blind, placebo-controlled trial conducted in Japan, Korea and Taiwan, eligible patients receiving low-dose ASA for cardiovascular protection (81-324 mg/day) were randomised to esomeprazole 20 mg/day or placebo for ≤72 weeks. All patients received concomitant mucosal protection (gefarnate 100 mg/day). The primary endpoint was time to ulcer recurrence (Kaplan-Meier analysis). Efficacy findings are presented up to week 48, as per a planned interim analysis within the study protocol. RESULTS: A total of 364 patients (79.9% men; mean age, 67.1 years) comprised the full analysis set (esomeprazole, n=182; placebo, n=182). There was a statistically significant difference in the time to ulcer recurrence between esomeprazole and placebo (HR 0.09; 96.65% CI 0.02 to 0.41; p<0.001). The estimated ulcer-free rate at week 12 was 99.3% (esomeprazole) and 89.0% (placebo). The high estimated ulcer-free rate for esomeprazole was maintained through to week 48 (98.3% vs. 81.2% of placebo-treated patients). No factors, other than female gender, reduced time to ulcer recurrence in addition to the effect of esomeprazole (p<0.001). Treatment with esomeprazole was generally well tolerated. CONCLUSIONS: Daily esomeprazole 20 mg is efficacious and well tolerated in reducing the recurrence of peptic ulcer in East-Asian patients with a history of ulcers who are taking low-dose ASA for cardiovascular protection. CLINICALTRIALGOV IDENTIFIER: NCT01069939.

Burden of nonsteroidal anti-inflammatory and antiplatelet drug use in Asia: a multidisciplinary working party report.

BACKGROUND & AIMS: We established a working group to examine the burden of atherothrombotic and musculoskeletal diseases in Asia and made recommendations for safer prescribing of nonsteroidal anti-inflammatory drugs (NSAIDs) and low-dose aspirin. METHODS: By using a modified Delphi process, consensus was reached among 12 multidisciplinary experts from Asia. Statements were developed by the steering committee after a literature review, modified, and then approved through 3 rounds of anonymous voting by using a 6-point scale from A+ (strongly agree) to D+ (strongly disagree). Agreement (A+/A) by ≥ 80% of panelists was defined a priori as consensus. RESULTS: We identified unique aspects of atherothrombotic and musculoskeletal diseases in Asia. Asia has a lower prevalence of degenerative arthritis and coronary artery disease than Western countries. The age-adjusted mortality of coronary artery disease is lower in Asia; cerebrovascular accident has higher mortality than coronary artery disease. Ischemia has replaced hemorrhage as the predominant pattern of cerebrovascular accident. Low-dose aspirin use is less prevalent in Asia than in Western countries. Traditional Chinese medicine and mucoprotective agents are commonly used in Asia, but their efficacy is not established. For Asian populations, little is known about complications of the lower gastrointestinal tract from use of NSAIDs and underutilization of gastroprotective agents. Our recommendations for preventing ulcer bleeding among users of these drugs who are at high risk for these complications were largely derived from Asian studies and are similar to Western guidelines. CONCLUSIONS: By using an evidence-based, multidisciplinary approach, we have identified unique aspects of musculoskeletal and atherothrombotic diseases and strategies for preventing NSAID-related and low-dose aspirin-related gastrointestinal toxicity in Asia.

Diagnosis and treatment of functional gastrointestinal disorders in the Asia-Pacific region: a survey of current practices.

BACKGROUND AND AIMS: Functional gastrointestinal disorders (FGIDs), namely functional dyspepsia (FD) and irritable bowel syndrome (IBS) are common disorders important to public health in the Asia-Pacific region. Our objectives were to determine the current practices in diagnosis and management of these disorders in the Asia-Pacific region. METHODS: Forty-three physicians and researchers in FGID who attended the first Asian Pacific Topic Conference at Tokyo in November 2010 were invited to answer a questionnaire. Twenty-three Japanese doctors and twenty doctors from other Asia-Pacific Societies answered the questionnaire, which consisted of 60 multiple-choice questions concerning physician's preferences in diagnosis and management of FGIDs. RESULTS: Overall, there were similarities in diagnostic approach, such as differential diagnosis, exclusion of organic diseases, psychophysiological assessment, medical advice or medication with psychological drugs, not only among different Asia-Pacific region but also between FD and IBS. Several notable differences were seen. For example, general practitioners did not commonly use the term FD or diagnose FD by themselves, while the term IBS was widely used and frequently diagnosed. Sub-categorization was more common in IBS than FD. There was also a difference between Japan and other Asia-Pacific region; upper GI endoscopy and blood examination were more common in Japan, while eradication of Helicobacter pylori was more frequently done in other countries. Anti-secretory drugs for FD and mild laxatives or anti-diarrheal drug for IBS were frequently used, and prokinetics were used for all patients with FD or IBS. Interestingly, drugs developed in Japan and Chinese herbal medicines were more frequently prescribed in Japan. CONCLUSION: Information obtained in this survey is useful for understanding the most common clinical approaches for FGIDs in the Asia-Pacific region.

Clinical efficacy of superfine dispersed lentinan (beta-1,3-glucan) in patients with hepatocellular carcinoma.

BACKGROUND/AIMS: Recently, complementary alternative medicine is actively performed for cancer therapy. We investigated the effectiveness of supplementary food containing superfine dispersed lentinan (beta-1,3-glucan) in patients with unresectable or recurrent hepatocellular carcinoma in a multi-center study. METHODOLOGY: Peripheral blood was collected prior to the test food ingestion and was incubated with fluorescein-labeled lentinan. The rates of lentinan-binding CD14+ monocytes were determined by flow cytometry. Patient survival times were followed up for 3 years. RESULTS: Thirty-six patients were eligible among 40 enrolled patients. Median survival time of eligible patients was 13.6 months (95% confidence interval, 8.7-18.9 months). Survival times of patients who ingested test food for a mean period of 47 weeks (range, 26 to 145 weeks) were significantly longer than that of patients who ingested for 7 to 12 weeks (p < 0.05). The rates of lentinan-binding cells in CD14+ monocytes showed individual variations (0.1-19.7%; Median, 1.6%). Survival times (median survival time, 16.3 months) of lentinan-high-binding group were significantly longer than those (median survival time, 12.5 months) of lentinan-low-binding group (p < 0.05). CONCLUSIONS: A superfine dispersed lentinan-containing supplementary food is effective for hepatocellular carcinoma patients' survival. Long-time ingestion is preferable. Assessment of lentinan-binding CD14+ monocytes is a promising prognostic predictor.

Asia-Pacific consensus guidelines on gastric cancer prevention.

BACKGROUND AND AIM: Gastric cancer is a major health burden in the Asia-Pacific region but consensus on prevention strategies has been lacking. We aimed to critically evaluate strategies for preventing gastric cancer. METHODS: A multidisciplinary group developed consensus statements using a Delphi approach. Relevant data were presented, and the quality of evidence, strength of recommendation, and level of consensus were graded. RESULTS: Helicobacter pylori infection is a necessary but not sufficient causal factor for non-cardia gastric adenocarcinoma. A high intake of salt is strongly associated with gastric cancer. Fresh fruits and vegetables are protective but the use of vitamins and other dietary supplements does not prevent gastric cancer. Host-bacterial interaction in H. pylori infection results in different patterns of gastritis and differences in gastric acid secretion which determine disease outcome. A positive family history of gastric cancer is an important risk factor. Low serum pepsinogens reflect gastric atrophy and may be useful as a marker to identify populations at high risk for gastric cancer. H. pylori screening and treatment is a recommended gastric cancer risk reduction strategy in high-risk populations. H. pylori screening and treatment is most effective before atrophic gastritis has developed. It does not exclude the existing practice of gastric cancer surveillance in high-risk populations. In populations at low risk for gastric cancer, H. pylori screening is not recommended. First-line treatment of H. pylori infection should be in accordance with national treatment guidelines. CONCLUSION: A strategy of H. pylori screening and eradication in high-risk populations will probably reduce gastric cancer incidence, and based on current evidence is recommended by consensus.