PURPOSE: Adjuvant chemotherapy after hepatectomy is controversial in liver-only metastatic colorectal cancer (CRC). We conducted a randomized controlled trial to examine if adjuvant modified infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) is superior to hepatectomy alone for liver-only metastasis from CRC. PATIENTS AND METHODS: In this phase II or III trial (JCOG0603), patients age 20-75 years with confirmed CRC and an unlimited number of liver metastatic lesions were randomly assigned to hepatectomy alone or 12 courses of adjuvant mFOLFOX6 after hepatectomy. The primary end point of phase III was disease-free survival (DFS) in intention-to-treat analysis. RESULTS: Between March 2007 and January 2019, 300 patients were randomly assigned to hepatectomy alone (149 patients) or hepatectomy followed by chemotherapy (151 patients). At the third interim analysis of phase III with median follow-up of 53.6 months, the trial was terminated early according to the protocol because DFS was significantly longer in patients treated with hepatectomy followed by chemotherapy. With median follow-up of 59.2 months, the updated 5-year DFS was 38.7% (95% CI, 30.4 to 46.8) for hepatectomy alone compared with 49.8% (95% CI, 41.0 to 58.0) for chemotherapy (hazard ratio, 0.67; 95% CI, 0.50 to 0.92; one-sided P = .006). However, the updated 5-year overall survival (OS) was 83.1% (95% CI, 74.9 to 88.9) with hepatectomy alone and 71.2% (95% CI, 61.7 to 78.8) with hepatectomy followed by chemotherapy. In the chemotherapy arm, the most common grade 3 or higher severe adverse event was neutropenia (50% of patients), followed by sensory neuropathy (10%) and allergic reaction (4%). One patient died of unknown cause after three courses of mFOLFOX6 administration. CONCLUSION: DFS did not correlate with OS for liver-only metastatic CRC. Adjuvant chemotherapy with mFOLFOX6 improves DFS among patients treated with hepatectomy for CRC liver metastasis. It remains unclear whether chemotherapy improves OS.

Aim: This study aimed to evaluate the association between surgeons certified via the Endoscopic Surgical Skill Qualification System (ESSQS) of the Japan Society for Endoscopic Surgery (JSES) and surgical outcomes of laparoscopic distal gastrectomy (LDG) and laparoscopic low anterior resection (LLAR).Methods: Japanese National Clinical Database data on the patients undergoing LDG and LLAR between 2014‐2016 were analyzed retrospectively. The proportion of cases performed by ESSQS‐certified surgeons was calculated for each procedure, and clinicopathological factors with or without participation of ESSQS‐certified surgeons as an operator were assessed. Then, effects of operations performed by ESSQS‐certified surgeons on short‐term patient outcomes were analyzed using generalized estimating equations logistic regression analysis.Results: There were 110 610 and 65 717 patients who underwent LDG and LLAR, respectively. The operations performed by ESSQS‐certified surgeons in each procedure totaled 28 467 (35.3%) and 12 866 (31.2%), respectively. A multivariable logistic regression model showed that odds ratios of mortality for LDG and LLAR performed by ESSQS‐certified surgeons were 0.774 (95% CI, 0.566‐1.060, P = 0.108) and 0.977 (0.591‐1.301, P = 0.514), respectively. Odds ratios for secondary endpoints of anastomotic leakage in LDG and LLAR performed by ESSQS‐certified surgeons were 0.835 (95% CI, 0.723‐0.964, P = 0.014) and 0.929 (0.860‐1.003, P = 0.059), respectively, whereas that of ileus/bowel obstruction for LLAR performed by ESSQS‐certified surgeons was 1.265 (1.132‐1.415, P < 0.001). There were no significant associations between the two operations performed by ESSQS‐certified surgeons and other factors such as mortality and overall complications.Conclusions: ESSQS certification did not affect postoperative mortality following LDG and LLAR, but annual experience of laparoscopic surgery was associated with it. ESSQS certification may contribute to favorable outcomes regarding anastomotic leakage following LDG and LLAR.