382 Background: Capecitabine is usually used for patients with curatively resected biliary tract cancer (BTC) in EU and US, but no clear survival benefit has been shown in phase III trials. S-1, an oral fluoropyrimidine derivative, has shown promising efficacy, with a mild toxicity profile, in patients with advanced BTC. The aim of this trial was to confirm whether adjuvant S-1 therapy might improve the overall survival (OS) in patients with curatively resected BTC. Methods: This open-label, multicenter, randomized phase III trial was conducted in 38 Japanese hospitals. Eligible patients were aged 20 to 80 years old, had undergone R0/R1 resection for histologically confirmed adeno(squamous) carcinoma of the extrahepatic bile duct, gallbladder or ampulla of Vater (T2-4, N0, M0 or T1-4, N1, M0) or the intrahepatic bile duct (T1-4, N0-1, M0) (7th UICC classification), and had an ECOG performance status (PS) of 0 or 1.The calculated sample size was 440 to detect hazard ratio for OS of 0.74 with one-sided alpha of 5% and a power of 80%. Patients in surgery-alone arm received no further anti-cancer treatment, while those in adjuvant S-1 arm received 4 cycles of oral S-1 chemotherapy at the dose of 40 mg/m² twice daily for 4 weeks, followed by 2 weeks of rest. Primary endpoint was OS, and secondary endpoints were relapse-free survival (RFS), incidence of adverse events, and proportion of treatment completion. Results: A total of 440 patients (surgery-alone, n = 222; adjuvant S-1, n = 218) were enrolled from September 2013 to June 2018. The data cutoff date was June 23, 2021, and the median follow-up duration was 45.4 months. Of all randomized patients, OS was significantly longer with adjuvant S-1 than surgery-alone (hazard ratio [HR] 0.694, 95%CI, 0.514-0.935; one-sided p = 0.008; the 3-year OS, 67.6% [surgery-alone; 95%CI, 61.0-73.3%] and 77.1% [adjuvant S-1; 95%CI, 70.9-82.1%]). Adjuvant S-1 was also better for RFS (HR 0.797 [95%CI, 0.613-1.035], 3-year RFS, 50.9% [surgery-alone; 95%CI, 44.1-57.2%] and 62.4% [adjuvant S-1; 95%CI, 55.6-68.4%]). All preplanned subgroup analyses (PS, age, cancer type, cancer stage, R factor, and serum CA19-9) revealed favorable OS and RFS for adjuvant S-1 arm. The main grade 3-4 adverse events in adjuvant S-1 arm were biliary tract infection (7.2%), diarrhea (2.9%), appetite loss (2.9%), fatigue (2.9%), and the treatment was well-tolerated. Conclusions: Adjuvant S-1 therapy led to significantly longer survival than surgery alone and becomes the standard of care for resected BTC. Clinical trial information: UMIN000011688.

Background: Traditionally, the treatment options for unresectable locally advanced (UR-LA) and metastatic (UR-M) pancreatic ductal adenocarcinoma (PDAC) are palliative chemotherapy or chemoradiotherapy. The benefits of surgery for such patients remains unknown. The present study investigated clinical outcomes of patients undergoing conversion surgery (CS) after chemo(radiation)therapy for initially UR-PDAC. Methods: We recruited patients with UR-PDAC who underwent chemo(radiation)therapy for initially UR-PDAC between April 2006 and September 2017. We analyzed resectability of CS, predictive parameters for overall survival, and early recurrence (within six months). Results: A total of 468 patients (108 with UR-LA and 360 with UR-M PDAC) were enrolled in this study, of whom, 17 (15.7%) with UR-LA and 15 (4.2%) with UR-M underwent CS. The median survival time (MST) and five-year survival of patients who underwent CS was 37.2 months and 34%, respectively; significantly better than non-resected patients (nine months and 1%, respectively, p < 0.0001). MST did not differ according to UR-LA or UR-M (50.5 vs. 29.0 months, respectively, p = 0.53). Early recurrence after CS occurred in eight patients (18.8%). Lymph node metastasis, positive washing cytology, large tumor size (>35 mm), and lack of postoperative adjuvant chemotherapy were statistically significant predictive factors for early recurrence. Moreover, the site of pancreatic lesion and administration of postoperative adjuvant chemotherapy were statistically significant prognostic factors for overall survival in the patients undergoing CS. Conclusion: Conversion surgery offers benefits in terms of increase survival for initially UR-PDAC for patients who responded favorably to chemo(radiation)therapy when combined with postoperative adjuvant chemotherapy.

The present study was conducted to determine whether active hexose correlated compound (AHCC), a functional food extracted from cultured basidiomycetes, possesses the potential to attenuate adverse events in unresectable pancreas ductal adenocarcinoma (PDAC) patients receiving chemotherapy. Unresectable PDAC patients receiving gemcitabine treatment (GEM) as the first-line chemotherapy were prospectively divided into 2 groups according to AHCC intake (AHCC group, n = 35) or not (control group, n = 40). The patients in the AHCC group ingested 6.0 g of AHCC for 2 mo. Hematological and nonhematological toxicity was compared between the AHCC and control groups. The C-reactive protein (CRP) elevation and albumin decline of the AHCC group were significantly suppressed as compared to the control group during the GEM administration (P = 0.0012, P = 0.0007). Patients in the AHCC group had less frequency of taste disorder caused by GEM (17% vs. 56%, P = 0.0007). Frequency of grade 3 in the modified Glasgow Prognostic Score (mGPS) during chemotherapy was found significantly less in the AHCC group (14%) than the control group (53%, P = 0.0005). AHCC intake can be effective in reducing the adverse events associated with chemotherapy and may contribute to maintaining the QOL of patients with PDAC during GEM administration.

Patients undergoing chemotherapy suffer from taste disorders that affect the quality of life (QOL). In this study, a randomized, double-blind, placebo-controlled trial was conducted to explore the effectiveness of AHCC^®, a standardized extract of cultured Lentinula edodes mycelia, for chemotherapy-related adverse events and taste disorders in patients with gastrointestinal cancer. Patients who received chemotherapy were randomized to receive either placebo or AHCC^®. The study endpoints were the incidence of anemia and taste disorders assessed with changes in nutritional parameters. Ninety-eight patients with pancreatic ductal adenocarcinoma (PDAC) were enrolled in this study, with 55 patients randomly assigned to the AHCC^® group and 43 to the placebo group. The incidence of grades 2-3 anemia in the AHCC^® group who were receiving chemotherapy was not significantly different compared to that of the placebo group (Risk difference; −3.1% [95% confidence intervals (CI): −22.8% to 16.9%], p = 0.8392). In the AHCC^® group, the occurrence of taste disorders during chemotherapy was significantly lower, and the nutritional parameters were significantly improved compared to those in the placebo group (Risk difference; 28.6% [95% CI: 7.5% to 47.8%], p = 0.0077). AHCC^® appears to prevent taste disorders in patients with advanced PDAC who were receiving chemotherapy. AHCC^® is expected to enable patients who need chemotherapy to improve nutritional status and their QOL.

Background/Aim: Recently, the Global Leadership Initiative on Malnutrition (GLIM), which includes the world’s leading clinical nutrition societies, proposed the first global diagnostic criteria for malnutrition. However, the association between malnutrition diagnosed by the GLIM criteria and prognosis in patients with resected extrahepatic cholangiocarcinoma (ECC) remains unknown. This study aimed to investigate the predictive validity of the GLIM criteria for the prognosis of patients with resected ECC. Patients and Methods: Between 2000 and 2020, 166 patients who underwent curative-intent resection for ECC were retrospectively analyzed. Prognostic significance of preoperative malnutrition diagnosed by the GLIM criteria was investigated using a multivariate Cox proportional hazards model. Results: Eighty-five (51.2%) and 46 (27.7%) patients were diagnosed with moderate and severe malnutrition, respectively. Increased malnutrition severity tended to be correlated with increased lymph node metastasis rate (p-for-trend=0.0381). The severe malnutrition group had worse 1-, 3-, and 5-year overall survival rates than the normal (without malnutrition) group (82.2% vs. 91.2%, 45.6% vs. 65.1%, 29.3% vs. 61.5%, respectively, p=0.0159). In multivariate analysis, preoperative severe malnutrition was an independent predictor for poor prognosis (hazard ratio=1.68, 95% confidence interval=1.06-2.66, p=0.0282), along with intraoperative blood loss >1,000 ml, lymph node metastasis, perineural invasion, and curability. Conclusion: Severe preoperative malnutrition diagnosed by the GLIM criteria was associated with poor prognosis in patients who underwent curative-intent resection for ECC.