Liang-Shuo Hu1, Xu-Feng Zhang1,2, Matthew Weiss3, Irinel Popescu4, Hugo P Marques5, Luca Aldrighetti6, Shishir K Maithel7, Carlo Pulitano8, Todd W Bauer9, Feng Shen10, George A Poultsides11, Oliver Soubrane12, Guillaume Martel13, B Groot Koerkamp14, Endo Itaru15, Timothy M Pawlik16. 1. Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. 2. Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, Surgery, Oncology, Health Services Management and Policy, The Ohio State University, Wexner Medical Center, Columbus, OH, USA. 3. Department of Surgery, Johns Hopkins Hospital, Baltimore, MD, USA. 4. Department of Surgery, Fundeni Clinical Institute, Bucharest, Romania. 5. Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal. 6. Department of Surgery, Ospedale San Raffaele, Milan, Italy. 7. Department of Surgery, Emory University, Atlanta, GA, USA. 8. Department of Surgery, Royal Prince Alfred Hospital, University of Sydney, Sydney, NSW, Australia. 9. Department of Surgery, University of Virginia, Charlottesville, VA, USA. 10. Department of Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai, China. 11. Department of Surgery, Stanford University, Stanford, CA, USA. 12. Department of Hepatobiliopancreatic Surgery and Liver Transplantation, AP-HP, Beaujon Hospital, Clichy, France. 13. Division of General Surgery, Department of Surgery, University of Ottawa, Ottawa, ON, Canada. 14. Department of Surgery, Erasmus University Medical Centre, Rotterdam, The Netherlands. 15. Gastroenterological Surgery Division, Yokohama City University School of Medicine, Yokohama, Japan. 16. Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, Surgery, Oncology, Health Services Management and Policy, The Ohio State University, Wexner Medical Center, Columbus, OH, USA. tim.pawlik@osumc.edu.
Abstract
BACKGROUND: Recurrence of intrahepatic cholangiocarcinoma (ICC) after curative resection is common. OBJECTIVE: The aim of this study was to investigate the patterns, timing and risk factors of disease recurrence after curative-intent resection for ICC. METHODS: Patients undergoing curative resection for ICC were identified from a multi-institutional database. Data on clinicopathological and initial operation information, timing and first sites of recurrence, recurrence management, and long-term outcomes were analyzed. RESULTS: A total of 920 patients were included. With a median follow-up of 38 months, 607 patients (66.0%) experienced ICC recurrence. In the cohort, 145 patients (23.9%) recurred at the surgical margin, 178 (29.3%) recurred within the liver away from the surgical margin, 90 (14.8%) recurred at extraheptatic sites, and 194 (32.0%) developed both intrahepatic and extrahepatic recurrence. Intrahepatic margin recurrence (median 6.0 m) and extrahepatic-only recurrence (median 8.0 m) tended to occur early, while intrahepatic recurrence at non-margin sites occurred later (median 14.0 m; p < 0.05). On multivariate analysis, surgical margin < 10 mm was associated with increased margin recurrence (hazard ratio [HR] 1.70, 95% confidence interval [CI] 1.11-2.60; p = 0.014), whereas female sex (HR 2.12, 95% CI 1.40-3.22; p < 0.001) and liver cirrhosis (HR 2.36, 95% CI 1.31-4.25; p = 0.004) were both associated with an increased risk of intrahepatic recurrence at other sites. Median survival after recurrence was better among patients who underwent repeat curative-intent surgery (48.7 months) versus other treatments (9.7 months) [p < 0.001]. CONCLUSIONS: Different recurrence patterns and timing of recurrence suggest biological heterogeneity of ICC tumor recurrence. Understanding timing and risk factors associated with different types of recurrence can hopefully inform discussions around adjuvant therapy, surveillance, and treatment of recurrent disease.
BACKGROUND: Recurrence of intrahepatic cholangiocarcinoma (ICC) after curative resection is common. OBJECTIVE: The aim of this study was to investigate the patterns, timing and risk factors of disease recurrence after curative-intent resection for ICC. METHODS:Patients undergoing curative resection for ICC were identified from a multi-institutional database. Data on clinicopathological and initial operation information, timing and first sites of recurrence, recurrence management, and long-term outcomes were analyzed. RESULTS: A total of 920 patients were included. With a median follow-up of 38 months, 607 patients (66.0%) experienced ICC recurrence. In the cohort, 145 patients (23.9%) recurred at the surgical margin, 178 (29.3%) recurred within the liver away from the surgical margin, 90 (14.8%) recurred at extraheptatic sites, and 194 (32.0%) developed both intrahepatic and extrahepatic recurrence. Intrahepatic margin recurrence (median 6.0 m) and extrahepatic-only recurrence (median 8.0 m) tended to occur early, while intrahepatic recurrence at non-margin sites occurred later (median 14.0 m; p < 0.05). On multivariate analysis, surgical margin < 10 mm was associated with increased margin recurrence (hazard ratio [HR] 1.70, 95% confidence interval [CI] 1.11-2.60; p = 0.014), whereas female sex (HR 2.12, 95% CI 1.40-3.22; p < 0.001) and liver cirrhosis (HR 2.36, 95% CI 1.31-4.25; p = 0.004) were both associated with an increased risk of intrahepatic recurrence at other sites. Median survival after recurrence was better among patients who underwent repeat curative-intent surgery (48.7 months) versus other treatments (9.7 months) [p < 0.001]. CONCLUSIONS: Different recurrence patterns and timing of recurrence suggest biological heterogeneity of ICC tumor recurrence. Understanding timing and risk factors associated with different types of recurrence can hopefully inform discussions around adjuvant therapy, surveillance, and treatment of recurrent disease.
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