Efficacy and safety of hangeshashinto for treatment of GERD refractory to proton pump inhibitors : Usual dose proton pump inhibitors plus hangeshashinto versus double-dose proton pump inhibitors: randomized, multicenter open label exploratory study.

BACKGROUND: Proton pump inhibitor (PPI)-refractory gastroesophageal reflux disease (GERD) leads to a clinical decline in the quality of life (QOL). Therefore, new treatment options are needed. We performed a multicenter, randomized, parallel-group exploratory trial to determine the efficacy of hangeshashinto (HST) in patients with PPI-refractory GERD. METHODS: We enrolled 78 patients with PPI-refractory GERD for standard PPI regimens for at least 4 weeks and randomly assigned patients to receive either a combination of usual dose of rabeprazole (10 mg/day) + HST (7.5 g/day; HST group) or a double dose of rabeprazole (20 mg/day; double-dose PPI group). The primary end points were the extent of improvement in FSSG (Frequency Scale for the Symptoms of GERD) score and the change over time in FSSG score. RESULTS: There was no significant difference in terms of the improvement degree of the FSSG score between the two groups. Although the total FSSG score and reflux syndrome score decreased significantly for both groups over time (p < 0.001), the acid-related dyspepsia (ARD) score decreased significantly in the HST group from 1 week after drug administration (p < 0.05), indicating an improvement in the condition earlier than in the double-dose PPI group. Moreover, in examinations concerning BMI and age, the HST group had a significantly higher improvement degree of ARD score in patients with BMI < 22 (p < 0.05) and aged < 65 years (p < 0.05) than the double-dose PPI group. CONCLUSIONS: HST may be beneficial for patients with PPI-refractory GERD, particularly in non-obese and non-elderly patients with dyspepsia symptoms.

The efficacy of the Kampo medicine rikkunshito for chemotherapy-induced anorexia (RICH trial): study protocol for a randomized controlled trial.

BACKGROUND: Cisplatin is a key drug in lung cancer therapy. However, cisplatin is also well known to induce gastrointestinal disorders, such as chemotherapy-induced nausea and vomiting, anorexia, and weight loss. These symptoms sometimes affect patients' quality of life and make continuation of chemotherapy difficult. Anorexia is a cause of concern for patients with cancer because a persistent loss of appetite progresses to cancer cachexia. Although evidence-based management for chemotherapy has recently been established, there is room for improvement. METHODS/DESIGN: This placebo-controlled, double-blind, randomized trial will aim to determine the efficacy of the traditional Japanese Kampo medicine rikkunshito (TJ-43) for preventing anorexia caused by cisplatin-including chemotherapy in patients with lung cancer. Patients with lung cancer who plan to receive cisplatin-including chemotherapy will be recruited. Patients who provide written consent will be randomly allocated to receive either TJ-43 (arm A) or placebo (arm B) for one course of chemotherapy (21 or 28 consecutive days). Investigators and patients will be masked to the treatment assignment throughout the trial. The primary endpoint will be evaluated as the change in dietary intake from day 0 (the day before the start of chemotherapy) to day 7 of cisplatin-including chemotherapy. The two arms of the trial will comprise 30 patients each. From November 2014, a total of 60 patients will be recruited, and recruitment for the study is planned to be complete by October 2017. DISCUSSION: This trial is designed to examine the efficacy of rikkunshito (TJ-43) for reducing anorexia and maintaining food intake caused by cisplatin-including chemotherapy in patients with lung cancer. TRIAL REGISTRATION: Japan Pharmaceutical Information Center Clinical Trials Information (JAPIC CTI), trial registration: JAPIC CTI-142747 . Registered on 15 December 2014; the RICH trial.

Intermittent fasting prompted recovery from dextran sulfate sodium-induced colitis in mice.

Fasting-refeeding in mice induces transient hyperproliferation of colonic epithelial cells, which is dependent on the lactate produced as a metabolite of commensal bacteria. We attempted to manipulate colonic epithelial cell turnover with intermittent fasting to prompt recovery from acute colitis. Acute colitis was induced in C57BL/6 mice by administration of dextran sulfate sodium in the drinking water for 5 days. From day 6, mice were fasted for 36 h and refed normal bait, glucose powder, or lactylated high-amylose starch. On day 9, colon tissues were subjected to analysis of histology and cytokine expression. The effect of lactate on the proliferation of colonocytes was assessed by enema in vivo and primary culture in vitro. Intermittent fasting resulted in restored colonic crypts and less expression of interleukin-1ß and interleukin-17 in the colon than in mice fed ad libitum. Administration of lactate in the colon at refeeding time by enema or by feeding lactylated high-amylose starch increased the number of regenerating crypts. Addition of lactate but not butyrate or acetate supported colony formation of colonocytes in vitro. In conclusion, intermittent fasting in the resolution phase of acute colitis resulted in better recovery of epithelial cells and reduced inflammation.

[Two cases of thymic carcinoid treated with octreotide long-acting repeatable].

Thymic carcinoid is a rare disease that accounts for 3.1% of thymic tumors and 1.8-6% of all carcinoid tumors in Japan. Advanced thymic carcinoid has a 5-year survival rate of 28-31%.Compared with carcinoid tumors that arise in other organs, thyroid carcinoid tumors carry a relatively worse prognosis, and the most effective therapeutic strategy is thought to be surgical resection.However, for patients with recurrence and distant metastases, multimodal therapy including radiotherapy and/or chemotherapy is usually applied.No chemotherapy treatment regimen has been established in Japan, although the National Comprehensive Cancer Network Guidelines proposed the application of octreotide long-acting repeatable(LAR).In this report, we present two cases of thymic carcinoid that were treated with octreotide LAR and achieved long-term survival.

Adult intussusception caused by Yersinia enterocolitica enterocolitis.

Yersinia enterocolitica (YE) infection is a rare cause of intestinal intussusception, especially in adults. We herein, report a case of adult intussusception due to YE enterocolitis. A 24-year-old woman was admitted because of severe abdominal pain. She was clinically diagnosed with ileocolic intussusception on the basis of the findings of computed tomography (CT) and a gastrografin enema. Manual surgical reduction was sufficient to alleviate the intussusception. A histological examination of the lymph nodes around the ileocecum excluded lymphoma. Serological testing revealed that the cause of the intussusception was a YE infection. The patient's postoperative course was good and no recurrence was seen during the follow-up.

Simvastatin attenuates intestinal fibrosis independent of the anti-inflammatory effect by promoting fibroblast/myofibroblast apoptosis in the regeneration/healing process from TNBS-induced colitis.

BACKGROUND: Intestinal deformity and stenosis are induced by fibrosis during the process healing of intestinal chronic inflammation in inflammatory bowel disease (IBD). Potent anti-inflammatory treatment of patients with Crohn's disease (CD) may induce fibrous stenosis, and this is often difficult to treat in clinical practice. Therefore, it is necessary to develop a treatment strategy that concomitantly exhibits repair/regenerative and anti-fibrotic effects, in addition to the current anti-inflammatory effect, for the treatment of inflammatory bowel diseases. However, the relationship between the course of inflammatory activity and the healing process and fibrogenesis has not been elucidated; although the complex involvement of various factors in the mechanism of biological fibrosis has been investigated. Simvastatin (SIMV), an HMG-CoA reductase inhibitor, exhibits anti-inflammatory and anti-fibrotic effects. The current study established a model of the regeneration/healing process from TNBS-induced colitis and investigated the anti-inflammatory and anti-fibrotic effects of SIMV. SUBJECTS AND METHODS: Four groups of TNBS-induced colitis model were prepared using male SJL/J mice: A: Normal control group, B: control group, and C and D: treatment groups. The mucosal healing process was classified into three phases (an early phase: inflammation period, a mid-phase: regeneration promoting period, and a late phase: regeneration-converging period), and inflammation, the expression of fibrosis-related growth factors, and induction of apoptosis of fibrosis-related cells were compared in each period. RESULTS: (1) The clinical findings showed that SIMV showed anti-inflammatory effects with body weight gain and improvement of epithelial injury in the late phase. Histological (macroscopic/microscopic) improvement was noted in the mid- and late phases. The inflammatory cytokine (TNF-α) level significantly decreased in the mid- and late phases in the high-dose treatment group. (2) SIMV also had anti-fibrotic effects characterized by a dose-dependent decrease in the level of a fibrosis-related growth factor (CTGF) in the early and mid-phases, irrespective of inflammation or changes in the TGF-ß(1) level. Dose-dependent induction of apoptosis was noted in both fibroblasts and myofibroblasts from a relatively early stage. CONCLUSIONS: The results suggested that SIMV induces anti-fibrotic activity that is not directly involved in the anti-inflammatory effect from a relatively early stage the healing process of TNBS-induced colitis.

R-etodolac induces E-cadherin and suppresses colitis-related mouse colon tumorigenesis.

Colorectal cancer is one of the most serious complications of ulcerative colitis (UC), and the risk of UC-associated neoplasia increases as the region and duration of the disease increase. Selective cyclooxygenase (COX)-2 inhibitors effectively diminish carcinogenesis in a murine UC model. However, this may exacerbate colitis. The selective COX-2 inhibitor etodolac is marketed as a racemic mixture of the R- and S-enantiomers. The biochemical and pharmacological effects of etodolac are caused by the S-enantiomer, while the R-enantiomer lacks COX-inhibitory activity. In this study, we evaluated the effect of R-etodolac on colitis-related mouse colon tumorigenesis. The mice received 1,2-dimethlhydrazine (DMH), and then chronic colitis was induced by administration of two cycles of DSS (each cycle: 3% DSS for 7 days followed by distilled water for 14 days). The mice were sacrificed 28 days after the completion of both cycles. Mice were divided into the following groups: group A served as a disease control; group B received a low (2-mg/kg) dose of R-etodolac every 3 days during the entire period; group C received a high (10-mg/kg) dose of R-etodolac on the same schedule as group B; and group D served as a normal control. Administration of R-etodolac decreased the disease activity index during the DSS administration cycle. The mean number of tumors was 17.8, 15.2, 6.0, and 0 in groups A-D, respectively. In group C, R-etodolac significantly suppressed the occurrence of neoplasia (p<0.05). Although R-etodolac treatment did not affect COX-2 expression, it significantly enhanced expression of E-cadherin in both neoplastic lesions and background mucosa (i.e., lesion-free colon). Thus, administration of R-etodolac exerts a suppressive effect on the development of neoplasia in a murine model of DSS-induced colitis without exacerbation of the colitis. These results suggest that R-etodolac could be useful in the prevention of UC-associated neoplasia.