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Safety of Combined Division vs Separate Division of the Splenic Vein in Patients Undergoing Distal PancreatectomyA Noninferiority Randomized Clinical Trial

Educational Objective
To identify via a noninferiority randomized clinical trial whether combined (vs separate) division of the splenic vein is safe in performing a distal pancreatectomy.
1 Credit CME
Key Points

Question  In distal pancreatectomy, is combined division of the splenic vein safe compared with separate division of the splenic vein?

Findings  In this noninferiority randomized clinical trial, the proportion of grade B/C pancreatic fistula in the separate division group was 27.1% vs 28.6% in the combined division group, demonstrating noninferiority of the combined division of the splenic vein against separate division.

Meaning  The safety of combined division of the splenic vein in distal pancreatectomy was established, such that the approach could be recommended with more confidence.


Importance  In distal pancreatectomy (DP), the splenic vein is isolated from the pancreatic parenchyma prior to being ligated and divided to prevent intra-abdominal hemorrhage from the splenic vein stump with pancreatic fistula (PF). Conversely, dissecting the splenic vein with the pancreatic parenchyma is easy and time-saving.

Objective  To establish the safety of combined division of the splenic vein compared with separate division of the splenic vein.

Design, Setting, and Participants  This study was designed as a multicenter prospective randomized phase 3 trial. All results were analyzed using the modified intent-to-treat set. Patients undergoing DP for pancreatic body and tail tumors were eligible for inclusion. Patients were randomly assigned between August 10, 2016, and July 30, 2019.

Interventions  Patients were centrally randomized (1:1) to either separate division of the splenic vein or combined division of the splenic vein.

Main Outcomes and Measures  The primary end point was the incidence of grade B/C PF, and the incidence of intra-abdominal hemorrhage was included as one of the secondary end points.

Results  A total of 318 patients were randomly assigned, and 2 patients were excluded as ineligible. Of the 316 remaining patients, 150 (50.3%) were male. The modified intent-to-treat population constituted 159 patients (50.3%) in the separate division group and 157 patients (49.7%) in the combined division group. In the modified intent-to-treat set, the proportion of grade B/C PF in the separate division group was 27.1% (42 of 155) vs 28.6% (44 of 154) in the combined division group (adjusted odds ratio, 1.108; 95% CI, 0.847-1.225; P = .047), demonstrating noninferiority of the combined division of the splenic vein against separate division. The incidence of postoperative intra-abdominal hemorrhage in the 2 groups was identical at 1.3%.

Conclusions and Relevance  This study demonstrated noninferiority of the combined division of the splenic vein compared with separate division of the splenic vein regarding safety. Thus, isolating the splenic vein from the pancreatic parenchyma is deemed unnecessary.

Trial Registration  ClinicalTrials.gov Identifier: NCT02871804

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Article Information

Corresponding Author: Hiroki Yamaue, MD, Second Department of Surgery, Wakayama Medical University, Kimiidera, Wakayama 641-8510, Japan (yamaue-h@wakayama-med.ac.jp).

Accepted for Publication: December 8, 2020.

Published Online: March 3, 2021. doi:10.1001/jamasurg.2021.0108

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Yamada S et al. JAMA Surgery.

Author Contributions: Dr Yamaue had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Drs Yamada and Fujii contributed equally.

Concept and design: Yamada, Fujii, Sonohara, Kawai, Baba, Satoi, Sho, Takeda, Shimokawa, Yamaue.

Acquisition, analysis, or interpretation of data: Yamada, Fujii, Sonohara, Shibuya, Matsumoto, Fukuzawa, Aoki, Unno, Satoi, Kishi, Hatano, Uemura, Horiguchi, Sho, Takeda, Shimokawa, Kodera, Yamaue.

Drafting of the manuscript: Yamada, Fujii, Sho, Takeda, Shimokawa, Yamaue.

Critical revision of the manuscript for important intellectual content: Fujii, Sonohara, Kawai, Shibuya, Matsumoto, Fukuzawa, Baba, Aoki, Unno, Satoi, Kishi, Hatano, Uemura, Horiguchi, Sho, Takeda, Shimokawa, Kodera, Yamaue.

Statistical analysis: Yamada, Kawai, Uemura, Shimokawa.

Obtained funding: Sonohara.

Administrative, technical, or material support: Fujii, Shibuya, Fukuzawa, Baba, Unno, Satoi, Hatano, Uemura, Horiguchi, Sho, Takeda, Yamaue.

Supervision: Fujii, Unno, Uemura, Sho, Takeda, Kodera, Yamaue.

Conflict of Interest Disclosures: Dr Unno reported grants from Taiho, Takeda, Chugai, Yakult, and Asahi Kasei outside the submitted work. Dr Kodera reported grants from Johnson & Johnson and Covidien outside the submitted work. No other disclosures were reported.

Funding/Support: The COSMOS-DP trial was funded by Wakayama Medical University.

Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Data Sharing Statement: See Supplement 3.

Additional Contributions: We thank Yuzo Yamamoto, MD (Akita University), Yasutsugu Takada, MD (Ehime University), and Yoshitsugu Tajima, MD (Shimane University), for data and safety monitoring, and Yasuyuki Suzuki, MD (Kagawa University), and Masaji Tani, MD (Shiga Medical University), for central judgment. We thank Mariko Doi and Megumi Kitayama in the Clinical Study Support Center, Wakayama Medical University, for preparing this protocol. No compensation was received. We thank Jane Charbonneau, DVM, from Edanz Group for editing a draft of this manuscript; compensation was received.

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