No Significant Effect of Daikenchuto (TJ-100) on Peritoneal IL-9 and IFN-γ Levels After Pancreaticoduodenectomy.

AIM AND BACKGROUND: TJ-100 is a traditional Japanese medicine that affects inflammation and gastrointestinal motility, and is used as a preventive and treatment for paralytic ileus. This study aims at determining the effect of TJ-100 on the peritoneal levels of IFN-γ/IL-9, cytokines related to ileus, after pancreaticoduodenectomy (PD) in a clinical setting. METHODS: This was a subsidiary study of the clinical trial investigating the effect of TJ-100 on postoperative bowel function. Ascites was collected from 180 patients using an abdominal drainage tube on postoperative day 1 and 3 after PD (POD 1 or POD 3) and used to measure 27 cytokines. We performed univariate and multivariate analyses using several perioperative variables and administration of TJ-100/placebo to determine the effect of TJ-100 on the levels of IFN-γ and IL-9. RESULTS: Peritoneal levels of IL-9 and IFN-γ decreased between POD 1 and 3 (Wilcoxon signed-rank test p<0.001). Multivariate analysis was performed after univariate analysis to select the variables and patients with a body mass index of ≥22 kg/m2, older age, use of epidural anesthesia, and longer surgery correlated with the levels of IL-9 and IFN-γ. However, we could not detect a correlation between the use of TJ-100 and cytokine levels in ascites either on POD 1 or 3. CONCLUSION: TJ-100 did not affect peritoneal IL-9 and IFN-γ levels after PD. This was in accordance with published clinical findings showing no improvement in bowel function after PD and TJ-100 treatment.

Transition of serum cytokines following pancreaticoduodenectomy: A subsidiary study of JAPAN-PD.

Our previous study aimed to examine the effect of TJ-100, a widely used herbal medicine, on intestinal function following pancreaticoduodenectomy (PD) in a multicenter, randomized, double-blinded, placebo-controlled manner (JAPAN-PD study). This concomitant study investigated the effect of TJ-100 on serum cytokine levels in patients who underwent PD. Due to the fact that several clinical variables can affect the absolute values of baseline serum cytokine levels, the ratios of the cytokine levels on postoperative day (POD)3 to those on POD1 were also used for analysis. The present study enrolled 180/224 randomized patients, of whom 91 received TJ-100 and 89 received placebo. As the main findings of the analysis, Wilcoxon signed-rank test revealed no significant difference in the levels of serum cytokines between the groups; however, patients in the TJ-100 group without severe inflammatory complications exhibited significantly higher ratios of interleukin (IL)-4 (n=123), IL-9 (n=72), IL-10 (n=97), PDGF-BB (n=143) and tumor necrosis factor-α (n=135), compared with patients in the Placebo Group (P<0.05). According to the results of the present study, TJ-100 has an effect on the change in serum cytokine levels from POD1 to POD3 following PD. However, the role of different transition pattern of cytokines in postoperative recovery following PD has to be investigated by further mechanical studies focusing on these extracted cytokines (ClinicalTrials.gov; no. NCT01607307; May 30, 2012).

Evaluation of the efficacy of daikenchuto (TJ -100) for the prevention of paralytic ileus after pancreaticoduodenectomy: A multicenter, double-blind, randomized, placebo-controlled trial.

BACKGROUND: We assessed the efficacy of TJ-100 taken perioperatively to recovery among patients with periampullary tumor or tumor of the head of the pancreas who underwent pancreaticoduodenectomy (PD). PATIENTS AND METHODS: In this multicenter, randomized, double-blinded, placebo-controlled, phase II trial (JAPAN-PD Study), patients were assigned randomly in a 1:1 ratio to receive TJ-100 or placebo. The coprimary endpoints were (1) incidence of postoperative paralytic ileus lasting >72 hours after surgery and (2) time to occurrence of postoperative paralytic ileus. This trial is registered at the UMIN Clinical Trials Registry (000007975) and at ClinicalTrials.gov (NCT01607307). RESULTS: From August 2012 through July 2013, we assessed 273 patients for eligibility, and 224 underwent randomization; 112 patients received TJ-100, and 112 patients received placebo. The population for analysis consisted of 104 patients who received TJ-100 and 103 who received placebo. Paralytic ileus occurred 35 (33.7%) in the TJ-100 group and 38 (36.9%) in the placebo group (P = .626). Time to first flatus was 2.25 (2.00-2.50) days in the TJ-100 group and 2.50 (1.50-2.50) days in the placebo group (P = .343). Among 23 patients who underwent a pylorus ring-preserving PD, time to first flatus was lower in the TJ-100 group than in the placebo group: 0.50 (0.50-1.00) days versus 1.50 (0.50-3.00) days (P = .034). CONCLUSION: Our findings suggest that use of TJ-100 did not improve recovery from paralytic ileus after PD, and may preclude the routine use of TJ-100 in clinical practice after PD operation.

Survival effects of adjuvant gemcitabine plus S-1 chemotherapy on pancreatic carcinoma stratified by preoperative resectability status.

BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the efficacy of adjuvant gemcitabine plus S-1(GS) chemotherapy for pancreatic carcinoma patients, stratified by the National Comprehensive Cancer Network (NCCN) preoperative resectability definition. METHODS: A total of 141 consecutive patients with resected pancreatic carcinoma who received adjuvant GS chemotherapy were evaluated retrospectively. According to the NCCN preoperative resectability definition, tumors were divided into resectable tumors (R group), borderline resectable tumors with portal vein contact (BR-PV group), and borderline resectable tumors with arterial contact (BR-A group). Overall survival and prognostic factors were analyzed. RESULTS: Overall 1-, 2-, and 5-year survival rates for the 141 patients were 89.6%, 69.9%, and 41.1%, respectively. Overall survival of the R group was significantly better than that of the BR-PV group and the BR-A group (P < 0.05). Overall 5-year survival rates of the R group, the BR-PV group, and the BR-A group were 49.0%, 25.0%, and 11.3%, respectively. Arterial contact (P = 0.020), preoperative CA 19-9 level ≥150 U/ml (P < 0.001), and positive nodal involvement (P = 0.025) were independent prognostic factors for poor overall survival. CONCLUSIONS: Adjuvant GS chemotherapy may provide a survival benefit especially for patients with resectable pancreatic carcinoma. J. Surg. Oncol. 2016;113:405-412. © 2016 Wiley Periodicals, Inc.

Perioperative antibiotics covering bile contamination prevent abdominal infectious complications after pancreatoduodenectomy in patients with preoperative biliary drainage.

BACKGROUND: Although bile contamination caused by preoperative biliary drainage (PBD) is a risk factor for infectious complications after pancreatoduodenectomy, the appropriate perioperative antibiotic regimen remains unclear. We evaluated a perioperative antibiotic strategy targeting bile contamination associated with PBD procedures for preventing abdominal infectious complications after pancreatoduodenectomy. METHODS: Consecutive patients (n = 254) underwent pancreatoduodenectomy at a single center. Perioperative antibiotics were mainly cefazolin in non-PBD cases (n = 116) and cefozopran in internal-PBD cases (n = 87). They were based on preoperative bile cultures in 51 of the external-PBD cases. Intraoperative bile cultures were examined prospectively. Morbidity and abdominal infectious complication rates were evaluated. RESULTS: The incidence of positive intraoperative bile cultures was significantly higher in the internal-PBD (85 %) and external-PBD (90 %) cases than in the non-PBD cases (26 %) (p < 0.001). The 91 % susceptibility to cefazolin for non-PBD was significantly higher than the 61 % for internal-PBD or 45 % for external-PBD (p < 0.001). Overall morbidity rates (23, 23, and 25 %) and abdominal infectious complications (13, 17, and 14 %) did not differ among the non-PBD, internal-PBD, and external-PBD cases, respectively. Only susceptibility to perioperative antibiotics of biliary microorganisms classified as resistant was a significant independent risk factor for abdominal infectious complications (p = 0.003). CONCLUSIONS: A perioperative antibiotic strategy particular to PBD procedures is valid for covering biliary microorganisms during pancreatoduodenectomy. Perioperative antibiotics covering bile contamination may prevent abdominal infectious complications after pancreatoduodenectomy in patients with and without PBD.