Daikenchuto significantly improves stool consistency and lower gastrointestinal symptoms in patients with chronic constipation.

Background and Aim: A number of basic and clinical studies have confirmed that the traditional Japanese herbal medicine, Daikenchutou (DKT) has a pharmacological effect on cholinergic and serotonergic mechanisms with a favorable safety profile and an improving effect on lower gastrointestinal (GI) symptoms including abdominal pain or bloating. The purpose of this study is to evaluate the efficacy and safety of DKT on chronic constipation. Methods: This multicenter, randomized, placebo-controlled, double-blinded clinical trial enrolled 67 patients with chronic constipation fulfilling Rome III criteria. After a 2-week observation period, 63 patients with persistent symptoms were finally randomized to a 4-week course of treatment with DKT or placebo. The primary endpoint consisted of a global assessment of overall treatment effect (OTE), while the secondary endpoints consisted of improvements in stool consistency, spontaneous bowel movements, lower GI symptoms related to constipation, and quality of life. Factors associated with OTE were also investigated. Results: After 4 weeks administration of DKT, OTE was significantly higher than placebo. No side effects were observed. Significant improvement in stool consistency and lower GI symptoms was observed in the DKT group. The improvements in lower GI symptoms as well as stool consistency were associated with OTE. OTE was higher in patients with greater improvement in lower GI symptoms with mental component summary scores close to normal before treatment. Conclusion: DKT was effective and safe in treating chronic constipation, especially in patients having symptoms related to constipation with no impaired mental component summary score.

Evidence-based clinical practice guidelines for gastroesophageal reflux disease 2021.

In Japan, with the increasing prevalence of gastroesophageal reflux disease (GERD) and growing public interest, the Japanese Society of Gastroenterology issued Evidence-based Clinical Practice Guidelines for GERD (1st edition) in 2009 and a revised 2nd edition in 2015. A number of studies on GERD were subsequently conducted in Japan and abroad, and vonoprazan, a potassium-competitive acid blocker (P-CAB), became available for the first time in Japan in February 2015. The revised 3rd edition (Japanese edition), which incorporates new findings and information, was published in April 2021. These guidelines are summarized herein, particularly sections related to the treatment of GERD. The important clinical issues addressed in the present revision are (i) the introduction of treatment algorithms that classify GERD into reflux esophagitis and non-erosive reflux disease, (ii) the clarification of treatment algorithms based on to the severity of reflux esophagitis, and (iii) the positioning of vonoprazan in the treatment for GERD. The present guidelines propose vonoprazan as the initial/maintenance treatment for severe reflux esophagitis. They also recommend vonoprazan or PPI as an initial treatment for mild reflux esophagitis and recommended PPI and proposed vonoprazan as maintenance treatment. These updated guidelines offer the best clinical strategies for GERD patients in Japan and hope that they will be of global use for the diagnosis and treatment for GERD.

Effects of Capsaicin on Older Patients with Oropharyngeal Dysphagia: A Double-Blind, Placebo-Controlled, Crossover Study.

BACKGROUND/AIMS: The standard of care for older patients with oropharyngeal dysphagia (OD) is poor. Stimulation of transient receptor potential vanilloid 1 might become a pharmacological strategy for these patients. This study aimed to compare the therapeutic effect of film food containing 0.75 µg of capsaicin in these patients. METHODS: In a crossover, randomized trial, 49 patients with OD were provided capsaicin or identical placebo at least 7 days apart. Patients' reported symptoms during repeated swallowing, the volume, pH and substance P (SP) concentrations in saliva, and cervical esophageal wall motion evaluated by ultrasonographic tissue Doppler imaging were obtained before and after capsaicin or placebo administration. RESULTS: Significantly more patients with OD who took capsaicin experienced improvement in symptoms than those who took placebo. Salivary SP levels were significantly increased after capsaicin administration compared with placebo in the effective group. The duration of cervical esophageal wall opening was significantly shorter in capsaicin administration in the effective group. Furthermore, a significant negative correlation was found between the duration of cervical esophageal wall opening and salivary SP levels. CONCLUSION: Elevated salivary SP concentrations stimulated by capsaicin greatly improve the safety and efficacy of swallowing, and shorten the swallow response in older patients with OD.

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.

Intragastric infusion of rikkunshito (kampo) induces proximal stomach relaxation in conscious dogs.

PURPOSE: Abnormal proximal gastric relaxation is one of the causes of functional dyspepsia. The purpose of this study is to use a barostat in conscious dogs to determine the effects of rikkunshito, which is considered to have beneficial effects on functional dyspepsia, on the proximal stomach. METHODS: Eight beagles were used. A gastrocutaneous fistula and force transducers were surgically implanted in the middle corpus and gastric antrum and duodenum, respectively. After a recovery period, a plastic bag was inserted through the gastrocutaneous fistula and the proximal stomach was distended using a barostat. First, four dogs were used to investigate the pressure-volume relation in the fasted and postprandial phases. Second, the stomachs of four different dogs were continuously distended at minimal distending pressure +2 mmHg, and 5 min later were infused with warmed liquid rikkunshito (2 g/20 mL) or water through the gastrocutaneous fistula. Finally, changes in the proximal gastric volume and gastrointestinal motility were observed. RESULTS: The proximal stomach was significantly more pliable in the postprandial phase than in the fasted phase. The proximal gastric volume increased immediately after liquid infusion under constant pressure in both phases and duodenal motility was accelerated. The effect of rikkunshito was significantly greater and lasted longer than that of water. No significant difference between the effects during the fasted or postprandial phase and no change in the gastric antrum motility were observed when rikkunshito was infused. CONCLUSION: These results indicate that rikkunshito accelerates duodenal motility and relaxes the proximal stomach.

Efficacy of Rikkunshito, a traditional Japanese medicine (Kampo), in treating functional dyspepsia.

BACKGROUND: Rikkunshito, a traditional Japanese (Kampo) medicine, is widely prescribed as an oral preparation for the treatment of functional dyspepsia (FD). In our previous study, we reported that extracorporeal ultrasonography (US) is a useful technique for the assessment of the gastric accommodation reflex (AR) and duodenogastric motility. In this study, we examined the effects of Rikkunshito on the gastroduodenal function in patients with FD. METHODS: Sixteen FD patients (median age, 45 y) underwent US, before and after 14 days of treatment with Rikkunshito (7.5 g b.d.). For assessment of the AR, a cross-sectional area of the proximal stomach was measured after incremental ingestion of a liquid meal up to 400-mL. The expansion rate was used as the parameter to determine the AR. Then, the gastric emptying rate (GER), motility index (MI), and reflux index (RI) were evaluated using previously reported methods. RESULTS: Although no significant changes were observed in the total score of the Gastrointestinal Symptom Rating Scale (GSRS), the scores of 3 of the 15 symptoms of GSRS decreased significantly after treatment with Rikkunshito. The expansion rate of the proximal stomach was significantly greater after treatment with Rikkunshito than before the treatment. Although the GER and MI increased significantly, no significant differences in the RI were observed after treatment with Rikkunshito. CONCLUSION: These observations suggested that Rikkunshito may be beneficial for the treatment of FD patients with impaired AR and gastric motility. These results also suggested that Rikkunshito has a therapeutic potential for FD and GERD.

Effect of daikenchuto (TU-100) on gastrointestinal and colonic transit in humans.

Daikenchuto (TU-100) is a traditional Japanese (Kampo) medicine used to treat postoperative ileus. TU-100 dose dependently increases gastrointestinal (GI) motility by modulating cholinergic and serotonergic mechanisms in animal studies. The aim of this study was to evaluate the effects of orally administered TU-100 on GI and colonic transit and bowel function in healthy humans. In a randomized, parallel-group, double-blind, placebo-controlled, dose-response study, 60 healthy subjects were randomly assigned to placebo or TU-100 2.5 g or 5 g tid ingested immediately before meals for 5 consecutive days. We measured GI and colonic transit by validated scintigraphy and stool frequency and consistency by daily diaries of bowel function. There were overall treatment effects on colonic filling at 6 h without any significant differences between each dose of TU-100 and placebo. There tended to be overall treatment effects on ascending colon (AC) emptying half-time; the TU-100 (7.5 g/day) treatment significantly accelerated AC emptying compared with placebo. There were numerically higher values of GC24 (which reflect overall colonic transit) with both doses of TU-100, but these changes were not statistically significant. There were no significant overall treatment effects on gastric emptying or stool frequency and consistency. One subject, who received 7.5 g/day of TU-100, had elevated creatine phosphokinase following the study. TU-100 (7.5 g/day) significantly accelerated AC emptying. Further randomized controlled trials in patients with functional constipation or irritable bowel syndrome with constipation are warranted to evaluate the clinical efficacy of TU-100 in these disorders.

Effects of aged garlic extract (AGE) on colorectal adenomas: a double-blinded study.

Aged garlic extract (AGE) is a material that has the possibility of a cancer-preventive effect according to epidemiologic and animal studies. In order to confirm the effects of AGE on colorectal adenomas, we conducted a double-blinded randomized study using high-AGE (AGE 2.4 ml/day) and low-AGE (AGE 0.16 ml/day) doses 1 groups. Fifty-one patients who were diagnosed as having colorectal adenomas by colonoscopy were randomly assigned to the high-AGE and low-AGE groups. The number and size of adenomas before intake (0 month) and 6 and 12 months after intake were measured using colonoscopy. In 37 patients chosen as efficacy evaluated subjects, 47.4% (9/19) in the high-AGE and 66.7% (12/18) in the low-AGE group had at least one new adenoma for the first and second interval (0 to 12 months after intake), and its relative risk was 0.71. The decrease rate of at least one adenoma was 50.0% (7/14) in the high-AGE group for the second interval (6 to 12 months after intake), whereas there was no decrease in subjects in the low-AGE group (p=0.02). The difference from the base-line for total size of adenomas increased in the low-AGE group, whereas an increase in the high-AGE group was suppressed for the second interval (p=0.04). The difference from the base-line for the total size of adenomas in subjects who had adenomas on the base-line increased in the low-AGE group and decreased in the high-AGE group for the second interval (p=0.03). The results of this study suggest the possibility of preventive and therapeutic effects of AGE on colorectal adenomas, though it is necessary to investigate these in larger-scale and longer-term trials.