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

Abstract

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).

Keywords: Daikenchuto; Kampo; herbal medicine; pancreatic cancer; tumor necrosis factor.

Figures

Figure 1.

Flow diagram of the study. Among 273 patients, 49 were excluded from randomization due to exclusion criteria (n=41), ineligibility (n=4) and declinature (n=4). Following randomization, a total of 17 patients were excluded from the primary analysis, as 13 patients did not undergo pancreatoduodenectomy, three did not receive protocol treatment and one patient withdrew consent.

Figure 2.

The ratios of cytokine levels on POD3 to those of POD1 were compared between the TJ-100 Group and the Placebo Group. A significant difference was observed in (A) IL-4, (B) IL-9, (C) IL-10, (D) PDGF-BB and (E) TNF-α. Dots represent the means and bars inside the boxes represent the medians of the ratios. IL, interleukin; TNF, tumor necrosis factor.