Safety of Combined Division vs Separate Division of the Splenic Vein in Patients Undergoing Distal Pancreatectomy

This noninferiority randomized clinical trial aims to establish the safety of combined division of the splenic vein compared with separate division of the splenic vein.

randomized study to establish the safety of this procedure so that it can be recommended with 71 more confidence. The use of this procedure will likely result in significant reductions in 72 operative time and blood loss during DP. Patients undergoing open or laparoscopic DP for pancreatic body and tail cancer, 78 intra-ductal papillary mucinous neoplasm, neuroendocrine tumours, mucinous cystic 79 neoplasm, or metastatic pancreatic tumours or similar are eligible for inclusion in this 80 study. In addition, simultaneous resection of the pancreatic parenchyma and splenic vein 81 in one session will be rendered possible through the evaluation of preoperative imaging 82 study findings. 83 84

2) Study design 85
This study is designed as a multicentre (45 institutes

1) Surgical resection 150
Before pancreatic transection, concurrent division of the splenic artery using a 151 mechanical stapler will not be permitted. A linear stapler, Endo GIA Reinforced Reload with 152 Tri-Staple Technology (Black Cartridge, Covidien ® ), will be used in all patients. The 153 pancreatic parenchyma will be compressed with the stapler at the planned line of resection 154 for over 5 minutes before transection is performed 7,8 . For the patients in Arm A, the splenic 155 vein will be isolated from the pancreatic parenchyma and dissected after ligation. For those 156 in Arm B, the splenic vein will be transected concurrently with the pancreatic parenchyma The presence of thrombus in the splenic vein will be evaluated at 1 and 6 months after 180 surgery by enhanced computed tomography or magnetic resonance imaging. Central monitoring will be performed each year by the data centre to evaluate the 186 study progress and ensure for study quality. The following aspects will be monitored: i) 187 data accumulation; ii) patient eligibility; iii) severe adverse events; iv) protocol deviations; 188 v) reasons for cessation or expiration of the protocol; vi) background factors of the 189 patients; and vii) other problems concerning study progress and safety.

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2) Audit 192 The person appointed by the audit office visits the participating institution and 193 confirms the study implementation system, and whether the study is conducted in a 194 ccordance with the study protocol and the ethical guidelines. All subjects for this study will be provided a consent form describing this study and providing 202 sufficient information for subjects to make an informed decision about their participation in this 203 study. The consent form will be submitted with the protocol for review and approval by the 204 Institutional Review Board (IRB) for the study. The formal consent of a subject, using the 205 IRB-approved consent form, must be obtained before that subject is submitted to any study 206 procedure. This consent form must be signed by the subject, and the investigator-designated 207 research professional obtaining the consent. A copy of the IRB-approved form must be kept 208 on-site and by administrative office and data center. This protocol and any amendments will be submitted to a properly constituted independent 212 IRB, in agreement with local legal prescriptions, for formal approval of the study conduct. The 213 decision of the IRB concerning the conduct of the study will be made in writing to the 214 investigator and a copy of this decision will be provided to administrative office and data The formal consent of a subject, using the IRB-approved consent form, must be obtained 226 before that subject is submitted to any study procedure. This consent form must be signed by 227 the subject. 228 229

3) Case registration 230
The investigator at each institution confirms the inclusion and exclusion criteria before surgery, 231 and then registers the subject of the data center. 232 233

4) Registration number 234
After confirming that the conditions are satisfied, the registration number is issued and 235 "registration" is completed at this point. If the input data is inadequate or does not meet the 236 eligibility criteria, the registration number will not be issued and it will not be "registered". 237 238

5) Allocation 239
When the case registration is made, the assigned group (A group or B group) and "registration 240 The research director or the investigator will start the protocol treatment within 28 days after 245 registration after confirming the completion of the case registration with "registration notice 246 form". If it is ineligible, the investigator explains to the subject that registration to this study is 247 not possible. 2. Expedited report of adverse events 348 1) All deaths "during protocol treatment" or "within 30 days after protocol treatment" 349

2) Unexpected Grade IV adverse events 350
An adverse event that is judged to be causally related to protocol treatment shall be subject to 351 expedited report. distributes emails about this adverse events to the research director of each institution to share 355 information. The principle investigator will report to the Efficacy and Safety Evaluation Committee 356 as soon as possible, and ask the judge about the adequacy of response to the adverse event. If the study is discontinued or suspended, the principal investigator must notify research director 444 of each institution, investigators, data center, Efficacy and Safety Assessment Committee, and the 445 persons concerned immediately. Investigators must notify subjects immediately. 446

3) Completion of the study 447
If the study is completed, the investigator will notify research director of each institution, 448