Rikkunshito increases peripheral incretin-hormone levels in humans and rats.

BACKGROUND: It was reported that rikkunshito (TJ-43) improved the cisplatin-induced decreases in the active form of ghrelin in plasma; however, other effects on gastrointestinal hormones have not been investigated. AIM: To investigate the effects of TJ-43 on peripheral levels of incretin hormones, including gastric inhibitory polypeptide (GIP) and glucagon-like polypeptide-1 (GLP-1), in humans and rats. METHODS: Patients were divided into two groups, namely patients who received TJ-43 immediately following surgery [TJ-43(+) group] and those who received TJ-43 on postoperative day 21 [TJ-43(-) group], and the plasma levels of active GIP and active GLP-1 were assessed. In animal experiments, rats were treated with TJ-43 [rat (r)TJ-43(+) group] or without [rTJ-43(-) group] by gavage for 4 wk, and the plasma active GIP and active GLP-1 levels were measured. The expression of incretin hormones in the gastrointestinal tract and insulin in the pancreas were investigated by immunohistochemistry. Furthermore, the cyclic adenosine monophosphate activities were assessed in pancreatic tissues from rats treated with or without TJ-43 in vivo, and the blood glucose levels and plasma insulin levels were measured in rats treated with or without TJ-43 in oral glucose tolerance tests. RESULTS: In humans, the active incretin hormone levels increased, and values were significantly greater in the TJ-43(+) group compared those in the TJ-43(-) group. In rats, the plasma active incretin levels significantly increased in the rTJ-43(+) group compared with those in the rTJ-43(-) group. GIP and GLP-1 expressions were enhanced by TJ-43 treatment. Moreover, plasma insulin levels increased and blood glucose levels were blunted in the rTJ-43(+) group. CONCLUSION: The results show that TJ-43 may be beneficial for patients who undergo pancreatic surgery.

Rikkunshito increases appetite by enhancing gastrointestinal and incretin hormone levels in patients who underwent pylorus-preserving pancreaticoduodenectomy: A retrospective study.

BACKGROUND: Rikkunshito (TJ-43) relieves gastrointestinal disturbance by increases in the levels of acylated ghrelin. AIM: To investigate the effects of TJ-43 in patients undergoing pancreatic surgery. METHODS: Forty-one patients undergoing pylorus-preserving pancreaticoduodenectomy (PpPD) were divided into two groups; patients took daily doses of TJ-43 after surgery or after postoperative day (POD) 21. The plasma levels of acylated and desacylated ghrelin, cholecystokinin (CCK), peptide YY (PYY), gastric inhibitory peptide (GIP), and active glucagon-like peptide (GLP)-1 were evaluated. Oral calorie intake was assessed at POD 21 in both groups. The primary endpoint of this study was the total food intake after PpPD. RESULTS: The levels of acylated ghrelin were significantly greater in patients treated with TJ-43 than those in patients without TJ-43 administration at POD 21, and oral intake was significantly increased in patients treated with TJ-43. The CCK and PYY levels were significantly greater in patients treated with TJ-43 than those in patients without TJ-43 treatment. Furthermore, the GIP and active GLP-1 levels increased and values at POD 21 were significantly greater in patients treated with TJ-43 than those in patients without TJ-43 administration. Insulin secretion tended to increase in patients treated with TJ-43. CONCLUSION: TJ-43 may have advantages for oral food intake in patients in the early phase after pancreatic surgery. Further investigation is needed to clarify the effects of TJ-43 on incretin hormones.

Prognostic value of preoperative psoas muscle index as a measure of nutritional status in patients with esophageal cancer receiving neoadjuvant therapy.

OBJECTIVES: It has been reported that preoperative nutritional status in some gastrointestinal cancers has a significant effect on postoperative prognosis. However, there are few reports on esophageal cancer, especially for esophageal cancer patients who have undergone neoadjuvant therapy and surgery. Psoas muscle index (PMI) is widely known as an index for assessing preoperative nutritional status, and has recently been reported for its prognostic value in many malignancies. The aim of this study was to investigate and evaluate the clinical results in our hospital using the PMI method. METHODS: We retrospectively investigated esophageal cancer in patients (clinical stage II or III) who underwent neoadjuvant therapy and surgical treatment (R0 cases) from January 2008 to December 2015. Applicable 63 cases were entered accordingly. In our hospital, nutritional supplements are used for nutritional management during preoperative adjuvant therapy, and these are administered to patients who have difficulty ingesting nutrition by feeding tube or total parenteral nutrition. The target value for nutritional supplement administration was 36 kcal/kg. Taking into account that chemotherapy for esophageal cancer was being performed using Harris-Benedict's basal energy expenditure (25 kcal/kg), we multiplied by 1.44 (active factor; 1.2, stress factor; 1.2) and set 36 kcal/kg as a guide. PMI was evaluated before neoadjuvant therapy and before surgery. We defined sarcopenia by PMI of the third lumbar vertebra (L3) by a computed tomography (CT) examination using 3-dimensional image analysis software, <6.36 for men and <3.92 for women, and investigated the effect of each on prognosis. RESULTS: The prevalence of sarcopenia decreased from 74.6% (47 of 63) to 69.84% (44 of 63) during the pretherapeutic to preoperative period (P = 0.691), suggesting improved nutritional status. Regarding PMI divided by cutoff value for each sex (the cutoff value was the PMI mean value -2 SD [6.36 cm2 m2 for men and 3.92 cm2/m2 for women] of healthy individuals <50 y of age, which was reported as a standard for low skeletal muscle mass in Japanese individuals), there was an improvement observed in the preoperative compared to pretherapeutic period, but it was not obtained as a significant difference (pretherapeutic PMI; 0.87 ± 0.06 [mean ± SD], preoperative PMI; 0.89 ± 0.06 [mean ± SD], P = 0.18). In overall survival (OS) and disease-free survival (DFS), there was no significant difference in the short-term results with and without sarcopenia in the pretherapeutic group (both OS and DFS, P = 0.17). There was a significant difference with and without sarcopenia in the preoperative group in terms of OS and DFS (OS, P = 0.045; DFS, P = 0.043), which was short term due to nutritional intervention during preoperative adjuvant therapy. It was suggested that the results would be improved. CONCLUSIONS: Improving nutritional status before surgery was shown to improve short-term prognosis in patients with esophageal cancer. It is hence suggested that it is important to maintain or improve nutritional status by intervention from the time of neoadjuvant therapy.

Medium-chain triglycerides enhance secretory IgA expression in rat intestine after administration of endotoxin.

The purpose of this study was to determine whether medium-chain triglycerides (MCTs) modulate the inflammatory immune response to LPS and enhance the expression of secretory IgA in the rat intestine. Rats were given either corn oil or MCTs by gavage daily for 1 wk, and LPS or saline vehicle was administered via the tail vein. They were then killed, and serum and sections from the gut were collected for further analysis. Western blot analysis for secretory IgA revealed that MCTs significantly enhanced its expression in the ileum compared with corn oil in rats administered saline. After LPS challenge, expression of secretory IgA was decreased in the corn oil group but not in the MCTs group. The mRNA expression of IL-6 was assessed by real-time RT-PCR, because IL-6 regulates secretory IgA in the intestine. The expression was significantly greater in the MCTs group than in the corn oil group after LPS injection. Increases in expression of proinflammatory cytokines or chemokines such as TNF-alpha, IL-18, macrophage inflammatory protein-2, and monocyte chemoattractant protein-1 in the ileum were significantly blunted by MCTs. In addition, the mRNA expression of the Th2 IgA-stimulating cytokine IL-10 in the ileum and Peyer's patches was significantly greater in the MCTs than the corn oil group. In contrast, the mRNA expression of the Th1 IgA-inhibiting cytokine interferon-gamma was blunted by MCTs. As a result, intestinal injury was significantly reduced. Therefore, MCTs protect the gut by modulating the immune response to LPS and enhancing secretory IgA expression.