Akihiko Horiguchi

BACKGROUND: Biliary tract cancer (BTC) is a type of malignancy that is challenging to manage. Further, advanced-stage BTC has poor prognosis. Based on the recent TOPAZ-1 trial, adding durvalumab to gemcitabine and cisplatin significantly improves survival in unresectable BTC, thereby making it the new standard first-line treatment. However, real-world data are essential to validate its efficacy and safety in routine clinical settings, which often involve older patients and those with comorbidities or previous therapies. This study aimed to evaluate the outcomes of combination chemotherapy with gemcitabine, cisplatin, and durvalumab (GCD) in a real-world cohort with BTC. METHODS: This retrospective analysis included patients with unresectable advanced-stage BTC treated with GCD between December 2022 and April 2024 at three institutions. GCD was administered for up to eight cycles, followed by durvalumab monotherapy. Clinical data, including the characteristics of the patients, adverse events, and treatment responses, were collected. The Kaplan-Meier method and the Cox proportional hazards model were used to assess progression-free survival (PFS), overall survival (OS), and other factors affecting outcomes. RESULTS: The current study included 54 patients with a median age of 72 years. Half of the patients had recurrence post-surgery, and many of them had previously received chemotherapy. The median PFS and OS rates were 4.1 and 8.0 months, respectively. Adverse events (AEs) were frequently observed, with 42.1% of patients presenting with grade 3 or higher AEs. However, immune-related AEs were rare and mild. Dose adjustments, which are often caused by renal impairment or fatigue, were common (66.7%). Multivariate analysis revealed that older age, a lower performance status score, and a high neutrophil-to-lymphocyte ratio (NLR) were significant predictors of a shorter PFS. Further, a lower performance status score, and a high NLR were associated with a low OS. CONCLUSIONS: GCD combination chemotherapy is a viable treatment option for advanced-stage BTC in a real-world setting where dose modifications can improve tolerability among elderly patients. Neutrophil-to-lymphocyte ratio can be a prognostic biomarker of OS in patients with BTC receiving immune checkpoint inhibitors. This finding highlights the potential of individualized treatment strategies. Nevertheless, further research should be performed to validate these results in larger cohorts.

BACKGROUND/AIM: Trifluridine/tipiracil (TAS-102) is a standard treatment for unresectable advanced or recurrent colorectal cancer. The incidence of grade 3 or higher neutropenia is high with the standard 5-day-on/2-day-off dosing schedule. Previous studies suggest that a 5-day-on/9-day-off (biweekly) schedule is associated with a lower incidence of neutropenia; however, direct comparative evidence is limited. This study aimed to retrospectively evaluate the impact of TAS-102 dosing schedules on safety. PATIENTS AND METHODS: Patients with colorectal cancer who received TAS-102 with/without bevacizumab with either the standard or biweekly schedule at three Fujita Health University-affiliated hospitals between June 2014 and January 2024 were included. The incidence of neutropenia, anemia, and thrombocytopenia based on the dosing schedule and renal function was retrospectively compared. The effect of dosing schedules on grade ≥3 neutropenia was also evaluated. RESULTS: Among 260 patients, 127 received the standard schedule, and 133 the biweekly schedule. Grade ≥3 neutropenia incidence was significantly lower with the biweekly schedule (26.3%) than with the standard schedule (40.2%) (p=0.0247). Multivariate analysis demonstrated that the standard schedule of TAS-102 was associated with a higher incidence of grade ≥3 neutropenia (p<0.01). Grade ≥3 anemia incidence was also lower with the biweekly schedule (13.5% versus 25.2%) (p=0.0187). Grade ≥3 neutropenia showed a trend towards a higher incidence in patients with estimated glomerular filtration rates ≥60 mL/min, at 29.4% compared with 41.0% in those with rates <60 ml/min (p=0.0679). CONCLUSION: The biweekly schedule of TAS-102 with/without bevacizumab was associated with a significantly lower incidence of grade ≥3 neutropenia than the standard schedule. This schedule may help patients - including those with impaired renal function - adhere to planned treatment regimens.

PURPOSE: This study aimed to clarify the current treatment status for biliary tract cancers based on data from the National Clinical Database (NCD) in Japan. METHODS: Total 3895 cases of biliary tract cancers registered in the NCD during 2021 were included. We identified the rates of resection, R0 resection, postoperative complications, and incidences of lymph node metastasis for gallbladder carcinoma, perihilar cholangiocarcinoma, distal bile duct carcinoma, and ampullary carcinoma. RESULTS: The number of biliary tract cancers registered in the NCD during 2021 was 3895 (1775 in extrahepatic bile duct carcinoma, 1422 in gallbladder carcinoma, and 698 in ampullary carcinoma). In gallbladder carcinoma, the resection (89.59%) and R0 resection rates (87.99%) were favorable, and the complication rate (6.05%) was lower than that of others. However, the postoperative complication rate could be higher in T3-T4 cases and when extrahepatic bile duct resection was performed concomitantly. Lymph node metastasis was frequently seen in 12.60% at the No. 13a lymph node. In perihilar cholangiocarcinoma, the R0 resection (69.82%) and complication rates (16.75%) were significantly lower and higher, respectively. In distal cholangiocarcinoma and ampullary carcinoma, metastasis was observed in approximately 2% and 10% of the dissected No. 16b1 para-aortic lymph nodes, respectively. In conclusion, although short-term surgical outcomes for biliary tract cancers in Japan might be acceptable, the significantly lower R0 resection and higher complication rates of perihilar cholangiocarcinomas indicate additional challenges for surgeons in the future and should continue to be monitored by the Japanese Society of Hepatobiliary and Pancreatic Surgery.

Abstract Aim The Japanese National Clinical Database, which covers more than 95% of the surgeries performed in Japan, is the largest nationwide database. This is the 2021 annual report of the Gastroenterological Section of the National Clinical Database, which aims to present the short‐term outcomes of cases registered in 2021 and discuss significant changes and insights into gastroenterological surgeries observed over the decade. Methods We reviewed the data of patients registered in the National Clinical Database between 2012 and 2021. Results In total, 5 788 093 cases, including 597 780 cases in 2021, were extracted from the National Clinical Database. The number of surgeries resumed its original trend after a uniform decrease due to the coronavirus disease 2019 pandemic. The patient population continues to age, and the proportion of female patients is steadily increasing. The trend of surgeries being conducted in certified institutions with the involvement of board‐certified surgeons is consistently rising. Moreover, the increasing trend of endoscopic surgery rate is still maintained. Although operative mortality is declining, the trend of increasing postoperative complications continues. Surgery on the esophagus, liver, and pancreas has shown substantial improvements in operative mortality, with a high participation rate of board‐certified surgeons. Surgical procedures with a high incidence of emergency surgeries are characterized by low participation rates of board‐certified surgeons, increased morbidity rates, and worse mortality outcomes. Conclusion This overview of surgical patients in Japan, obtained using data extracted from the National Clinical Database, may serve as a critical cornerstone for the future development of gastroenterological surgery.