Preventive effect of 20 mEq and 8 mEq magnesium supplementation on cisplatin-induced nephrotoxicity: a propensity score-matched analysis.

PURPOSE: The protective effect of magnesium (Mg) supplementation against cisplatin (CDDP)-induced nephrotoxicity has been widely described; however, the optimal dose of Mg supplementation is unclear. The aim of this study was to investigate whether 20 mEq of Mg supplementation is more effective than 8 mEq Mg in preventing CDDP-induced nephrotoxicity, as well as the associated risk factors, in cancer patients treated with CDDP-based chemotherapy. METHODS: Pooled data of 272 patients receiving 20 mEq or 8 mEq Mg supplementation to CDDP-based chemotherapy from a multicenter, retrospective, observational study were compared using propensity score matching. Separate multivariate logistic regression analyses were used to identify the risk factors for renal failure induced by each treatment dose. RESULTS: There was no significant difference in the incidence of nephrotoxicity between the 8 mEq and 20 mEq groups (P = 0.926). There was also no significant difference in the severity of nephrotoxicity, elevated serum creatinine levels, and decreased estimated creatinine clearance levels between the two groups. Cardiac disease and albumin levels were identified as independent risk factors for CDDP-induced nephrotoxicity. CONCLUSION: We did not find an advantage of 20 mEq over 8 mEq Mg supplementation in terms of a preventive effect against CDDP-induced nephrotoxicity. The optimal dose of Mg supplementation for the prevention of CDDP-induced nephrotoxicity remains unknown, and further studies are warranted.

Risk Factors for Cisplatin-Induced Nephrotoxicity: A Multicenter Retrospective Study.

INTRODUCTION: Cisplatin (CDDP)-induced nephrotoxicity is a concern in CDDP-based chemotherapy. The goal of this multicenter retrospective study was to identify potential risk factors for CDDP nephrotoxicity. METHODS: Clinical data were reviewed for 762 patients who underwent chemotherapy including CDDP ≥60 mg/m2 per day from Spring 2014 to September 2016. CDDP nephrotoxicity was defined according to the National Cancer Institute Common Terminology Criteria for Adverse Events for acute kidney injury. Univariate and multivariate logistic regression analyses were performed to identify risk factors for CDDP nephrotoxicity. RESULTS: CDDP nephrotoxicity was observed in 165 patients (21.7%). Multivariate analysis showed a significantly higher rate of CDDP nephrotoxicity in patients with cardiac disease (odds ratio [OR]: 2.05, 95% confidence interval [CI]: 1.07-3.93, p = 0.03), hypertension (OR: 1.57, 95% CI: 1.06-2.32, p = 0.02), and high-dose CDDP therapy (OR: 2.15, 95% CI: 1.50-3.07, p < 0.01). Magnesium (Mg) supplementation (OR: 0.65, 95% CI: 0.45-0.93, p = 0.02) and diuretic use (OR: 0.22, 95% CI: 0.08-0.63, p < 0.01) were also independent risk factors for CDDP nephrotoxicity. CONCLUSIONS: Our results suggest that high-dose CDDP and comorbidities of cardiac disease and hypertension are independent risk factors for CDDP nephrotoxicity. Therefore, close monitoring of serum creatinine values during CDDP treatment is recommended for patients with these risk factors. In addition, Mg supplementation and administration of diuretics might be effective for prevention of CDDP nephrotoxicity.

Effects of BARLEYmax and high-ß-glucan barley line on short-chain fatty acids production and microbiota from the cecum to the distal colon in rats.

We investigated whether supplementation with the barley line BARLEYmax (Tantangara; BM), which contains three fermentable fibers (fructan, ß-glucan, and resistant starch), modifies the microbiota in cecal and distal colonic digesta in addition to short-chain fatty acids (SCFAs) production more favorably than supplementation with a high-ß-glucan barley line (BG012; BG). Male Sprague-Dawley rats were randomly divided into 3 groups that were fed an AIN-93G-based diet that contained 5% fiber provided by cellulose (control), BM or BG. Four weeks after starting the respective diets, the animals were sacrificed and digesta from the cecum, proximal colon and distal colon were collected and the SCFA concentrations were quantified. Microbiota in the cecal and distal colonic digesta were analyzed by 16S rRNA sequencing. The concentrations of acetate and n-butyrate in cecal digesta were significantly higher in the BM and BG groups than in the control group, whereas the concentration of total SCFAs in cecal digesta was significantly higher only in the BM group than in the control group. The concentrations of acetate and total SCFAs in the distal colonic digesta were significantly higher only in the BM group than in the control group. The abundance of Bacteroidetes in cecal digesta was significantly higher in the BM group than in the control group. In contrast, the abundance of Firmicutes in cecal digesta was significantly lower in the BM and BG groups than in the control group. These results indicated that BM increased the concentration of total SCFAs in the distal colonic digesta. These changes might have been caused by fructan and resistant starch in addition to ß-glucan. In conclusion, fermentable fibers in BM reached the distal colon and modified the microbiota, leading to an increase in the concentration of total SCFAs in the distal colonic digesta, more effectively compared with the high-ß-glucan barley line (BG).

The effects of the herbal medicine Daikenchuto (TJ-100) after esophageal cancer resection, open-label, randomized controlled trial.

BACKGROUND: Daikenchuto (TJ-100), a traditional Japanese herbal medicine, is widely used in Japan. Its effects on gastrointestinal motility and microcirculation and its anti-inflammatory effect are known. The purpose of this prospective randomized controlled trial was to investigate the effect of TJ-100 after esophagectomy in esophageal cancer patients. METHODS: Forty patients for whom subtotal esophageal resection for esophageal cancer was planned at our institute from March 2011 to August 2013 were enrolled and divided into two groups at the point of determination of the operation schedule after informed consent was obtained: a TJ-100 (15 g/day)-treated group (n = 20) and a control group (n = 20). The primary efficacy end-points were maintenance of the nutrition condition and the recovery of gastrointestinal function. The secondary efficacy end-points were the serum C-reactive protein (CRP) level and adrenomedullin level during the postoperative course, the incidence of postoperative complications, and the length of hospital stay after surgery. RESULTS: We examined 39 patients because one patient in the TJ-100 group was judged as having unresectable cancer after surgery. The mean age of the TJ-100 group patients was significantly older than that of the control group patients.The rate of body weight decrease at postoperative day 21 was significantly suppressed in the TJ-100 group (3.6% vs. the control group: 7.0%, p = 0.014), but the serum albumin level was not significantly different between the groups. The recovery of gastrointestinal function regarding flatus, defecation, and oral intake showed no significant between-group differences, but postoperative bowel symptoms tended to be rare in the TJ-100 group. There was no significant between-group difference in the length of hospital stay after surgery. The serum CRP level at postoperative day 3 was 4.9 mg/dl in the TJ-100 group and 6.9 mg/dl in the control group, showing a tendency of a suppressed serum CRP level in the TJ-100 group (p = 0.126). The rate of increase in adrenomedullin tended to be high postoperatively, but there was no significant difference between the two groups. CONCLUSIONS: TJ-100 treatment after esophageal cancer resection has the effects of prompting the recovery of gastrointestinal motility and minimizing body weight loss, and it might suppress the excess inflammatory reaction related to surgery.

Triterpenes augment the inhibitory effects of anticancer drugs on growth of human esophageal carcinoma cells in vitro and suppress experimental metastasis in vivo.

The antineoplastic effects of combinations of anticancer drugs (5-fluorouracil, irinotecan and cisplatin) and triterpenes (ursolic acid, betulinic acid, oleanolic acid and a Japanese apricot extract (JAE) containing triterpenes) on esophageal squamous carcinoma cells were examined by the WST-8 (2-(2-methoxy- 4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt) assay in vitro and by an animal model in vivo. Triterpenes and JAE showed additive and synergistic cytotoxic effects, respectively, on esophageal squamous carcinoma cells (YES-2 cells) by combinational use of 5-fluorouracil. JAE and 5-fluorouracil induced cell cycle arrest at G2/M phase and at S phase, respectively, and caused apoptosis in YES-2 cells. A new animal model of esophageal cancer causing tumor colonization of the peritoneal cavity and producing bloody ascites was made by injecting YES-2 cells into the peritoneal cavity of a severe combined immunodeficiency mouse. In this model, 5-fluorouracil inhibited colonization of tumor cells in the peritoneum. The addition of JAE to 5-fluorouracil augmented the suppression of experimental metastasis of the peritoneum. The numbers of peritoneal nodules of more than 2 mm in diameter in mice treated with 5-fluorouracil and JAE were less than those in mice treated with 5-fluorouracil alone or JAE alone. These results suggest that triterpenes, especially JAE, are effective supplements for enhancing the chemotherapeutic effect of 5-fluorouracil on esophageal cancer.