Daikenchuto accelerates the recovery from prolonged postoperative ileus after open abdominal surgery: a subgroup analysis of three randomized controlled trials.

PURPOSE: Prolonged postoperative ileus (POI) is a common complication after open abdominal surgery (OAS). Daikenchuto (DKT), a traditional Japanese medicine that peripherally stimulates the neurogenic pathway, is used to treat prolonged POI in Japan. To analyze whether DKT accelerates the recovery from prolonged POI after OAS, we conducted a secondary analysis of three multicenter randomized controlled trials (RCTs). METHODS: A secondary analysis of the three RCTs supported by the Japanese Foundation for Multidisciplinary Treatment of Cancer (project numbers 39-0902, 40-1001, 42-1002) assessing the effect of DKT on prolonged POI in patients who had undergone OAS for colon, liver, or gastric cancer was performed. The subgroup included 410 patients with no bowel movement (BM) before the first diet, a DKT group (n = 214), and a placebo group (n = 196). Patients received either 5 g DKT or a placebo orally, three times a day. The primary endpoint was defined as the time from the end of surgery to the first bowel movement (FBM). A sensitivity analysis was also performed on the age, body mass index and dosage as subgroup analyses. RESULTS: The primary endpoint was significantly accelerated in the DKT group compared with the placebo group (p = 0.004; hazard ratio 1.337). The median time to the FBM was 113.8 h in the placebo group and 99.1 h in the DKT treatment group. CONCLUSIONS: The subgroup analysis showed that DKT significantly accelerated the recovery from prolonged POI following OAS. TRIAL REGISTRATION NUMBER: UMIN000026292.

ctDNA-based molecular residual disease and survival in resectable colorectal cancer.

The interim analysis of the CIRCULATE-Japan GALAXY observational study demonstrated the association of circulating tumor DNA (ctDNA)-based molecular residual disease (MRD) detection with recurrence risk and benefit from adjuvant chemotherapy (ACT) in resectable colorectal cancer (CRC). This updated analysis with a 23-month median follow-up, including 2,240 patients with stage II-III colon cancer or stage IV CRC, reinforces the prognostic value of ctDNA positivity during the MRD window with significantly inferior disease-free survival (DFS; hazard ratio (HR): 11.99, P < 0.0001) and overall survival (OS; HR: 9.68, P < 0.0001). In patients who experienced recurrence, ctDNA positivity correlated with shorter OS (HR: 2.71, P < 0.0001). The significantly shorter DFS in MRD-positive patients was consistent across actionable biomarker subsets. Sustained ctDNA clearance in response to ACT was an indicator of favorable DFS and OS compared to transient clearance (24-month DFS: 89.0% versus 3.3%; 24-month OS: 100.0% versus 82.3%). True spontaneous clearance rate with no clinical recurrence was 1.9% (2/105). Overall, our findings provide evidence for the utility of ctDNA monitoring for post-resection recurrence and mortality risk stratification that could be used for guiding adjuvant therapy.