Wenbo Meng1, Joseph W Leung2, Kai Zhang3, Wence Zhou4, Zhenyu Wang4, Leida Zhang5, Hao Sun6, Ping Xue7, Wei Liu8, Qi Wang9, Jijun Zhang10, Xuefeng Wang11, Meng Wang12, Yingmei Shao13, Kailin Cai14, Senlin Hou15, Qiyong Li16, Lei Zhang17, Kexiang Zhu4, Ping Yue1, Haiping Wang18, Ming Zhang3, Xiangyu Sun19, Zhiqing Yang5, Jie Tao6, Zilong Wen7, Qunwei Wang9, Bendong Chen20, Quan Shao10, Mingning Zhao11, Ruoyan Zhang12, Tiemin Jiang13, Ke Liu14, Lichao Zhang15, Kangjie Chen21, Xiaoliang Zhu17, Hui Zhang4, Long Miao4, Zhengfeng Wang4, Jiajia Li18, Xiaowen Yan18, Fangzhao Wang22, Lingen Zhang22, Azumi Suzuki23, Kiyohito Tanaka23, Ula Nur24, Elisabete Weiderpass25, Xun Li26. 1. Department of Special Minimally Invasive Surgery, CHESS Center, The First Hospital of Lanzhou University, Lanzhou, China; Hepatopancreatobiliary Surgery Institute of Gansu Province, Clinical Medical College Cancer Center of Lanzhou University, Lanzhou, China; Key Laboratory of Biological Therapy and Regenerative Medicine Transformation Gansu Province, Lanzhou, China. 2. Division of Gastroenterology and Hepatology, University of California, Davis Medical Center and Sacramento Veterans Affairs Medical Center, Sacramento, CA, USA. 3. Hepatobiliary Surgery Department, Shandong Provincial Third Hospital, Jinan, China. 4. Second Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, China; Hepatopancreatobiliary Surgery Institute of Gansu Province, Clinical Medical College Cancer Center of Lanzhou University, Lanzhou, China; Key Laboratory of Biological Therapy and Regenerative Medicine Transformation Gansu Province, Lanzhou, China. 5. Department of Hepatobiliary Surgery, Southwest Hospital, Army Medical University, Chongqing, China. 6. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. 7. Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. 8. Minimal Invasive Surgery Centre, Second Xiangya Hospital, Central South University, Changsha, China. 9. Minimal Invasive Surgery Centre, Second Xiangya Hospital, Central South University, Changsha, China; Department of Hepatobiliary Surgery, The General Hospital of Ningxia Medical University, Yinchuan, Ningxia, China. 10. Department of General Surgery, Sixth Hospital of Shanxi Medical University (General Hospital of TISCO), Taiyuan, China. 11. Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Biliary Tract Disease Research, Shanghai, China. 12. Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun, China. 13. Department of Hepatobiliary and Hydatid, Digestive and Vascular Surgery Centre, Xinjiang Key Laboratory of Echinococcosis and Liver Surgery Research, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China. 14. Gastrointestinal Surgery Department, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 15. Department of Biliopancreatic Endoscopic Surgery, Second Hospital of Hebei Medical University, Shijiazhuang, China. 16. Division of Hepatobiliary and Pancreatic Surgery, School of Medicine, Shulan (Hangzhou) Hospital, Zhejiang University, Hangzhou, China. 17. Fifth Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, China; Hepatopancreatobiliary Surgery Institute of Gansu Province, Clinical Medical College Cancer Center of Lanzhou University, Lanzhou, China; Key Laboratory of Biological Therapy and Regenerative Medicine Transformation Gansu Province, Lanzhou, China. 18. Hepatopancreatobiliary Surgery Institute of Gansu Province, Clinical Medical College Cancer Center of Lanzhou University, Lanzhou, China; Key Laboratory of Biological Therapy and Regenerative Medicine Transformation Gansu Province, Lanzhou, China. 19. Centre of Minimally Invasive Surgery, Tianjin Nankai Hospital, Tianjin, China. 20. Department of Hepatobiliary Surgery, The General Hospital of Ningxia Medical University, Yinchuan, Ningxia, China. 21. Division of Hepatobiliary and Pancreatic Surgery, School of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, China. 22. Second Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, China. 23. Department of Gastroenterology, Kyoto Second Red Cross Hospital, Kyoto, Japan. 24. Department of Public Health, College of Health Sciences, Qatar University Health, Qatar University, Doha, Qatar. 25. International Agency for Research on Cancer, Lyon, France. 26. Fifth Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, China; Hepatopancreatobiliary Surgery Institute of Gansu Province, Clinical Medical College Cancer Center of Lanzhou University, Lanzhou, China; Key Laboratory of Biological Therapy and Regenerative Medicine Transformation Gansu Province, Lanzhou, China. Electronic address: drlixun@163.com.
Abstract
BACKGROUND:Endoscopic sphincterotomy is the established treatment for common bile duct stones. Balloon dilation offers an alternative. Prolonged dilation (300 s) with a 10 mm diameter balloon decreases the occurrence of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). We aimed to determine the optimal duration of dilation for combined endoscopic sphincterotomy and balloon dilation for the removal of common bile duct stones. METHODS: We did a multicentre, single-blinded, randomised controlled trial at 15 tertiary surgical centres in China. Eligible patients (≥18 years) with native papilla and common bile duct stones (≤1·5 cm in size and <2 cm in diameter) undergoing ERCP were randomly assigned (1:1:1:1:1) to receive balloon dilation for 0, 30, 60, 180, or 300 s after deep bile duct cannulation. Randomisation was done by an independent statistician using a computer-generated randomisation list with a block size of ten, stratified by centre. Patients and outcome assessors, but not endoscopists and investigators, were masked to treatment allocation. Balloon dilation was done with controlled radial expansion balloons according to common bile duct stone size. Stones were removed using stone retrieval balloons or baskets. The primary endpoint was overall frequency of post-ERCP pancreatitis. The primary efficacy analysis and safety analyses were done in the modified intention-to-treat population, which included all randomly assigned patients with successful cannulation, but excluded those who withdrew consent after randomisation. This study was registered with ClinicalTrials.gov, number NCT02510495, and is complete. FINDINGS:Between July 29, 2015, and Dec 1, 2017, 3721 consecutive patients with common bile duct stones were recruited, 1718 of whom were excluded. The remaining 2003 patients underwent a small (3-5 mm) endoscopic sphincterotomy. 83 patients withdrew consent after the ERCP procedure, thus 1920 patients were included in the modified intention-to-treat analysis (0 s [n=371], 30 s [n=384], 60 s [n=388], 180 s [n=390], and 300 s [n=387]). Overall, post-ERCP pancreatitis occurred in 199 (10%) of 1920 patients (44 [12%] patients in the 0 s group, 28 [7%] in the 30 s group, 32 [8%] in the 60 s group, 36 [9%] in the 180 s group, and 59 [15%] in the 300 s group). Prolonged dilation (300 s) significantly increased the occurrence of post-ERCP pancreatitis compared with shorter balloon dilation (p=0·002). The frequency of post-ERCP pancreatitis was significantly lower in the 30, 60, and 180 s groups than in the 300 s group (relative risk [RR] 0·48, 95% CI 0·31-0·73; p=0·0005 vs the 30 s group; 0·54, 0·36-0·81; p=0·003 vs the 60 s group; 0·61, 0·41-0·89; p=0·01 vs the 180 s group). The frequency of post-ERCP pancreatitis was significantly higher in the 0 s group than the 30 s group (RR 1·62, 1·04-2·56; p=0·03). No difference in stone extraction (all ≥90%) was observed between groups. Following ERCP, 90 (5%) of 1920 patients had acute cholangitis, 14 (<1%) had acute cholecystitis, and five (<1%) had gastrointestinal bleeding, with no significant differences between groups. One (<1%) patient had Stapfer II perforation, which resolved spontaneously with conservative treatment. INTERPRETATION: A balloon dilation time of 30 s for combined endoscopic sphincterotomy and balloon dilation reduced the frequency of post-ERCP pancreatitis and was determined to be the optimum dilation time for the removal of common bile duct stones. FUNDING: National Natural Science Foundation of China, Gansu Competitive Foundation Projects for Technology Development and Innovation.
RCT Entities:
BACKGROUND: Endoscopic sphincterotomy is the established treatment for common bile duct stones. Balloon dilation offers an alternative. Prolonged dilation (300 s) with a 10 mm diameter balloon decreases the occurrence of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). We aimed to determine the optimal duration of dilation for combined endoscopic sphincterotomy and balloon dilation for the removal of common bile duct stones. METHODS: We did a multicentre, single-blinded, randomised controlled trial at 15 tertiary surgical centres in China. Eligible patients (≥18 years) with native papilla and common bile duct stones (≤1·5 cm in size and <2 cm in diameter) undergoing ERCP were randomly assigned (1:1:1:1:1) to receive balloon dilation for 0, 30, 60, 180, or 300 s after deep bile duct cannulation. Randomisation was done by an independent statistician using a computer-generated randomisation list with a block size of ten, stratified by centre. Patients and outcome assessors, but not endoscopists and investigators, were masked to treatment allocation. Balloon dilation was done with controlled radial expansion balloons according to common bile duct stone size. Stones were removed using stone retrieval balloons or baskets. The primary endpoint was overall frequency of post-ERCP pancreatitis. The primary efficacy analysis and safety analyses were done in the modified intention-to-treat population, which included all randomly assigned patients with successful cannulation, but excluded those who withdrew consent after randomisation. This study was registered with ClinicalTrials.gov, number NCT02510495, and is complete. FINDINGS: Between July 29, 2015, and Dec 1, 2017, 3721 consecutive patients with common bile duct stones were recruited, 1718 of whom were excluded. The remaining 2003 patients underwent a small (3-5 mm) endoscopic sphincterotomy. 83 patients withdrew consent after the ERCP procedure, thus 1920 patients were included in the modified intention-to-treat analysis (0 s [n=371], 30 s [n=384], 60 s [n=388], 180 s [n=390], and 300 s [n=387]). Overall, post-ERCP pancreatitis occurred in 199 (10%) of 1920 patients (44 [12%] patients in the 0 s group, 28 [7%] in the 30 s group, 32 [8%] in the 60 s group, 36 [9%] in the 180 s group, and 59 [15%] in the 300 s group). Prolonged dilation (300 s) significantly increased the occurrence of post-ERCP pancreatitis compared with shorter balloon dilation (p=0·002). The frequency of post-ERCP pancreatitis was significantly lower in the 30, 60, and 180 s groups than in the 300 s group (relative risk [RR] 0·48, 95% CI 0·31-0·73; p=0·0005 vs the 30 s group; 0·54, 0·36-0·81; p=0·003 vs the 60 s group; 0·61, 0·41-0·89; p=0·01 vs the 180 s group). The frequency of post-ERCP pancreatitis was significantly higher in the 0 s group than the 30 s group (RR 1·62, 1·04-2·56; p=0·03). No difference in stone extraction (all ≥90%) was observed between groups. Following ERCP, 90 (5%) of 1920 patients had acute cholangitis, 14 (<1%) had acute cholecystitis, and five (<1%) had gastrointestinal bleeding, with no significant differences between groups. One (<1%) patient had Stapfer II perforation, which resolved spontaneously with conservative treatment. INTERPRETATION: A balloon dilation time of 30 s for combined endoscopic sphincterotomy and balloon dilation reduced the frequency of post-ERCP pancreatitis and was determined to be the optimum dilation time for the removal of common bile duct stones. FUNDING: National Natural Science Foundation of China, Gansu Competitive Foundation Projects for Technology Development and Innovation.
Authors: Kleyton Santos de Medeiros; Ana Clara Aragão Fernandes; Giuliana Fulco Gonçalves; Camila Vilar Oliveira Villarim; Laura Cristina Costa E Silva; Victor Matheus Câmara de Sousa; Amália Cinthia Meneses Rêgo; Irami Araújo-Filho Journal: Medicine (Baltimore) Date: 2022-09-30 Impact factor: 1.817