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).

[A Case of Advanced Hepatocellular Carcinoma, Its Disease Progression Could Be Controlled by Multimodal Treatment].

The patient was a 73-year-old man, diagnosed with advanced huge hepatocellular carcinoma with a tumor thrombus extending into the inferior vena cava and extrahepatic metastases. Radiation therapy(50 Gy)was applied for the bone metastases, primary tumor, and tumor thrombus, and the patient received a cisplatin transcatheter arterial infusion(100mg/ body, 5 courses). Sorafenib was administered orally once the local lesion was under control. The tumor showed a partial response according to the RECIST criteria, but the tumor thrombus in the inferior vena cava almost disappeared. The presence of a tumor thrombus in the inferior vena cava must be regarded as an oncologic emergency. Acisplatin transcatheter arterial infusion and radiation therapy may be treatment options for unresectable cases.

Proposed preoperative risk factors for early recurrence in patients with resectable pancreatic ductal adenocarcinoma after surgical resection: A multi-center retrospective study.

BACKGROUND/OBJECTIVE: Although surgical resection remains the only chance for cure in patients with pancreatic ductal adenocarcinoma (PDAC), postoperative early recurrence (ER) is frequently encountered. The purpose of this study is to determine the preoperative predictive factors for ER after upfront surgical resection. METHODS: Between 2001 and 2012, 968 patients who underwent upfront surgery with R0 or R1 resection for PDAC at seven high-volume centers in Japan were retrospectively reviewed. ER was defined as relapse within 6 months after surgery. Study analysis stratified by resectable (R) and borderline resectable (BR) PDACs was conducted according to the National Comprehensive Cancer Network guidelines. RESULTS: ER occurred in 239 patients (25%) with a median survival time (MST) of 8.8 months. Modified Glasgow prognostic score = 2 (odds ratio (OR) 2.06, 95% confidence interval (CI) 1.05-3.95; P = 0.044), preoperative CA19-9 ≥300 U/ml (OR 1.94, 1.29-2.90; P = 0.003), and tumor size ≥30 mm (OR 1.72, 1.16-2.56; P = 0.006), were identified as preoperative independent predictive risk factors for ER in patients with R-PDAC. In the R-PDAC patients, MST was 35.5, 26.3, and 15.9 months in patients with 0, 1 and ≥2 risk factors, respectively. There were significant differences in overall survival between the three groups (P < 0.001). No preoperative risk factors were identified in BR-PDAC patients with a high rate of ER (39%). CONCLUSIONS: There is a high-risk subset for ER even in patients with R-PDAC and a simple risk scoring system is useful for prediction of ER.

[Resection of the remnant pancreas for recurrent pancreatic cancer after distal pancreatectomy-a case report].

The standard treatment for metastatic pancreatic cancer is chemotherapy. The effect of surgical resection for localized recurrence in the remnant pancreas after pancreatectomy for pancreatic cancer is unknown, but is reported to have a moderately good outcome in a few reports. We herein report a case of curative resection for recurrence in the remnant pancreas, 24 months after distal pancreatectomy for pancreatic cancer. A 71-year-old man was diagnosed with pancreas tail cancer. Neoadjuvant treatment with chemoradiotherapy[ weekly full-dose gemcitabine(GEM) and radiation therapy 50 Gy/25 Fr] was followed by distal pancreatectomy. Postoperative adjuvant therapy with hepatic arterial infusion of 5-FU and systemic GEM therapy was completed. Twenty-four months after surgery, follow-up computed tomography scan results showed a lesion of 15-mm diameter in the remnant pancreas. Resection of the remnant pancreas was performed. The pathological findings showed moderately differentiated adenocarcinoma, morphologically similar to the primary pancreatic cancer. Six months following surgery, there are no signs of recurrence at present.

[A case of postoperative multiple liver metastases of pancreatic cancer successfully treated by combination chemotherapy with weekly high-dose 5-FU hepatic arterial infusion plus systemic infusion of gemcitabine].

We report a case of a 65-year-old man with postoperative multiple liver metastases of pancreatic cancer successfully treated with weekly high-dose 5-FU hepatic arterial infusion chemotherapy plus systemic infusion of gemcitabine. The patient was admitted because of suffering from epigastralgia and jaundice. He underwent pancreaticoduodenectomy for pancreatic head cancer and received postoperative adjuvant chemotherapy of gemcitabine. Abdominal CT after 6 months showed multiple liver metastases. Then we started a systemic gemcitabine (1,000 mg/body) infusion and weekly high- dose 5-FU (1,500 mg/body) hepatic arterial infusion chemotherapy. After 26 times of treatment, CT indicated that the tumors completely disappeared. He survived for 34 months after surgery. It has been suggested that this combined chemotherapy might be an effective treatment to control liver metastases of pancreatic cancer.