Comparison of Kimura Versus Warshaw Technique for Laparoscopic Spleen-Preserving Distal Pancreatectomy

Comparison of Kimura Versus Warshaw Technique for Laparoscopic Spleen-Preserving Distal Pancreatectomy: A Multicenter Randomized Controlled Clinical Trial

This study aims to compare the surgical outcomes of laparoscopic spleen-preserving distal pancreatectomy using the Kimura technique versus the Warshaw technique. The primary focus is on the rates of unplanned splenectomy, occurrence of severe complications, as well as intraoperative and perioperative outcomes of both techniques.

Study Overview

• Status: Not yet recruiting
• Conditions: Pancreatic Neuroendocrine Tumor; Solid Pseudopapillary Tumor of the Pancreas; Pancreatic Tumor, Benign
• Intervention / Treatment: Procedure: Laparoscopic spleen-preserving distal pancreatectomy using the Kimura technique; Procedure: Laparoscopic spleen-preserving distal pancreatectomy using the Warshaw technique

Detailed Description

For benign and low-grade malignant tumors of the pancreatic body and tail, laparoscopic distal pancreatosplenectomy (LDP) is commonly recommended due to its shorter hospital stay, lower intraoperative blood loss, and comparable complication rates. The DIPLOMA international multicenter clinical trial further established the non-inferiority of minimally invasive techniques in terms of curative resection for resectable pancreatic body and tail cancers.

As the spleen plays a crucial role in immune defense, splenectomy is associated with increased postoperative infection risk, significant increase in platelet count, and thrombosis. Therefore, for benign and low-grade malignant tumors of the pancreatic body and tail, minimally invasive spleen-preserving distal pancreatectomy should be the preferred approach.

The Kimura technique is the most commonly used and favored spleen-preserving distal pancreatectomy technique. It involves the complete preservation of splenic vessels, resulting in fewer postoperative complications. However, it is time-consuming and challenging due to the identification and ligation of numerous small and short vessels entering the pancreatic body and tail to preserve the fragile splenic artery and vein. On the other hand, the Warshaw technique involves segmental resection of splenic vessels and relies on the left gastroepiploic artery and short gastric vessels for splenic perfusion. It is a simpler procedure with less intraoperative blood loss and shorter operative time. However, it carries an increased risk of postoperative splenic infarction, gastric varices, and secondary bleeding.

Although a higher incidence of splenic infarction has been observed with the Warshaw technique, its clinical relevance remains controversial. Reports indicate that approximately 25% of patients undergoing Warshaw procedure show radiological evidence of asymptomatic gastric varices, but during a follow-up period of up to 21 years, no clinically relevant consequences of gastric varices were observed. Most cases of postoperative splenic infarction are transient and do not require specific treatment. Data from a large pan-European retrospective study showed no significant differences in the clinical incidence of splenic infarction (0.6% vs. 1.6%, P = 0.127) and major complication rates (11.5% vs. 14.4%, P = 0.308) between minimally invasive Kimura and Warshaw techniques.

While Kimura and Warshaw techniques demonstrate comparability in most postoperative outcomes, the former appears to have an advantage in reducing the risk of splenic infarction and gastric varices. Some experts propose a "Kimura-first" strategy. However, there is currently no prospective study comparing these two techniques. Therefore, this study has designed a multicenter randomized controlled clinical trial, focusing on the rates of unplanned splenectomy, severe complication occurrence, and intraoperative and perioperative outcomes of laparoscopic spleen-preserving distal pancreatectomy using the Kimura versus the Warshaw technique. Long-term follow-up will assess clinically relevant outcomes such as splenic ischemia, splenic hyperfunction, gastric varices, and postoperative quality of life. This study aims to provide higher-level evidence in the selection of laparoscopic spleen-preserving distal pancreatectomy techniques.

• Study Type: Interventional
• Enrollment (Estimated): 240
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xianjun Yu, MD, PhD; Phone Number: +86-13801669875; Email: yuxianjun@fudanpci.org
• Study Contact Backup: Name: Zheng Li, MD; Phone Number: +86-18521097686; Email: lizheng@fudanpci.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age between 18 and 70 years, regardless of gender.
• Preoperative clinical diagnosis of benign or low-grade malignant pancreatic tumors.
• Meeting the recommended surgical indications as per guidelines.
• Feasibility of imaging assessment for either Kimura or Warshaw technique laparoscopic spleen-preserving distal pancreatectomy.
• Performance status of 0 or 1 according to the Eastern Cooperative Oncology Group (ECOG) score.
• Willingness to comply with the study treatment plan, follow-up schedule, and other protocol requirements.
• Voluntarily participating in the study and signing an informed consent form.

Exclusion Criteria:

• Body Mass Index (BMI) > 28 kg/m2 (Chinese obesity standard).
• History of blood disorders, acute or chronic pancreatitis, gastrointestinal bleeding, splenic rupture, or gastric varices (preoperative CT indicating curved vessel structures along the gastric wall with a diameter > 5mm).
• History of abdominal surgery.
• Concomitant primary malignant tumors.
• Suspicion of malignancy based on PET-CT or other imaging examinations.
• Severe impairment of cardiac, liver, or kidney function (NYHA class 3-4, ALT and/or AST exceeding three times the upper limit of normal, Creatinine exceeding the upper limit of normal).
• Planned pregnancy or pregnancy and lactating women.
• Participants currently involved in other clinical trials.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Kimura group; Laparoscopic spleen-preserving distal pancreatectomy using the Kimura technique.	Procedure: Laparoscopic spleen-preserving distal pancreatectomy using the Kimura technique; The laparoscopic spleen-preserving distal pancreatectomy using the Kimura technique is defined as a surgical procedure that aims to remove the distal part of the pancreas while preserving the spleen by maintaining the splenic artery and vein (Hepatogastroenterology. 2003;50:2242).
Active Comparator: Warshaw group; Laparoscopic spleen-preserving distal pancreatectomy using the Warshaw technique.	Procedure: Laparoscopic spleen-preserving distal pancreatectomy using the Warshaw technique; Warshaw technique laparoscopic spleen-preserving distal pancreatectomy is defined as a surgical procedure that aims to preserve the spleen while removing the distal part of the pancreas. It involves ligating the splenic artery and vein, while preserving the left gastroepiploic artery and short gastric vessels (Arch Surg. 1988;123:550).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Unplanned splenectomy rate	The unplanned splenectomy rate in both groups will be calculated, and detailed records of the specific reasons will be documented, such as adhesions, bleeding, intraoperative splenic infarction.	Immediately after the surgery.
Severe complication rate	The rate of severe complications will be assessed by evaluating the severity of postoperative complications using the Clavien-Dindo classification system. In this classification system, complications graded as III and above are considered severe complications.	Within 90 days after surgery.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Spleen vessel preservation rate	The spleen vessel preservation rate refers to the rate at which the spleen vessels are successfully preserved during surgery. In cases where the Kimura technique is unable to preserve the spleen vessels, salvage Warshaw procedure or splenectomy may be performed. This can include modified Warshaw procedures that involve the simple removal of the splenic artery or splenic vein.	Immediately after the surgery.
Postoperative Clinically Relevant Spleen Ischemia (CRSI) rate	CRSI is defined as the occurrence of spleen ischemia requiring splenectomy during either the initial hospitalization or subsequent readmissions. The reasons for the second splenectomy will be recorded.	Through study completion, an average of 3 year.
Postoperative quality of life assessment	The evaluation will be conducted using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30). The EORTC QLQ-C30 is a widely used questionnaire to assess the quality of life. It consists of multiple scales and items that cover various aspects of physical functioning, role functioning, emotional functioning, cognitive functioning, social functioning, global health status, and symptom scales. Each item in the questionnaire is rated on a four-point Likert scale, ranging from 1 (not at all) to 4 (very much). Some items are reverse-scored, meaning that a higher score indicates a worse outcome. The scores for each scale are then transformed to a 0-100 scale, where a higher score represents a better outcome for functioning scales and a worse outcome for symptom scales.	Through study completion, an average of 3 year.

Collaborators and Investigators

• Sponsor: Fudan University
• Collaborators: Tongji Hospital; Qilu Hospital of Shandong University; Tianjin Medical University Cancer Institute and Hospital; The Third Affiliated Hospital of Soochow University
• Investigators: Principal Investigator: Xianjun Yu, MD, PhD, Fudan University

Publications and helpful links

General Publications

• de Rooij T, van Hilst J, van Santvoort H, Boerma D, van den Boezem P, Daams F, van Dam R, Dejong C, van Duyn E, Dijkgraaf M, van Eijck C, Festen S, Gerhards M, Groot Koerkamp B, de Hingh I, Kazemier G, Klaase J, de Kleine R, van Laarhoven C, Luyer M, Patijn G, Steenvoorde P, Suker M, Abu Hilal M, Busch O, Besselink M; Dutch Pancreatic Cancer Group. Minimally Invasive Versus Open Distal Pancreatectomy (LEOPARD): A Multicenter Patient-blinded Randomized Controlled Trial. Ann Surg. 2019 Jan;269(1):2-9. doi: 10.1097/SLA.0000000000002979.
• Asbun HJ, Moekotte AL, Vissers FL, Kunzler F, Cipriani F, Alseidi A, D'Angelica MI, Balduzzi A, Bassi C, Bjornsson B, Boggi U, Callery MP, Del Chiaro M, Coimbra FJ, Conrad C, Cook A, Coppola A, Dervenis C, Dokmak S, Edil BH, Edwin B, Giulianotti PC, Han HS, Hansen PD, van der Heijde N, van Hilst J, Hester CA, Hogg ME, Jarufe N, Jeyarajah DR, Keck T, Kim SC, Khatkov IE, Kokudo N, Kooby DA, Korrel M, de Leon FJ, Lluis N, Lof S, Machado MA, Demartines N, Martinie JB, Merchant NB, Molenaar IQ, Moravek C, Mou YP, Nakamura M, Nealon WH, Palanivelu C, Pessaux P, Pitt HA, Polanco PM, Primrose JN, Rawashdeh A, Sanford DE, Senthilnathan P, Shrikhande SV, Stauffer JA, Takaori K, Talamonti MS, Tang CN, Vollmer CM, Wakabayashi G, Walsh RM, Wang SE, Zinner MJ, Wolfgang CL, Zureikat AH, Zwart MJ, Conlon KC, Kendrick ML, Zeh HJ, Hilal MA, Besselink MG; International Study Group on Minimally Invasive Pancreas Surgery (I-MIPS). The Miami International Evidence-based Guidelines on Minimally Invasive Pancreas Resection. Ann Surg. 2020 Jan;271(1):1-14. doi: 10.1097/SLA.0000000000003590.
• Korrel M, Jones LR, van Hilst J, Balzano G, Bjornsson B, Boggi U, Bratlie SO, Busch OR, Butturini G, Capretti G, Casadei R, Edwin B, Emmen AMLH, Esposito A, Falconi M, Groot Koerkamp B, Keck T, de Kleine RHJ, Kleive DB, Kokkola A, Lips DJ, Lof S, Luyer MDP, Manzoni A, Marudanayagam R, de Pastena M, Pecorelli N, Primrose JN, Ricci C, Salvia R, Sandstrom P, Vissers FLIM, Wellner UF, Zerbi A, Dijkgraaf MGW, Besselink MG, Abu Hilal M; European Consortium on Minimally Invasive Pancreatic Surgery (E-MIPS). Minimally invasive versus open distal pancreatectomy for resectable pancreatic cancer (DIPLOMA): an international randomised non-inferiority trial. Lancet Reg Health Eur. 2023 Jul 6;31:100673. doi: 10.1016/j.lanepe.2023.100673. eCollection 2023 Aug.
• Casciani F, Trudeau MT, Vollmer CM Jr. Perioperative Immunization for Splenectomy and the Surgeon's Responsibility: A Review. JAMA Surg. 2020 Nov 1;155(11):1068-1077. doi: 10.1001/jamasurg.2020.1463.
• Korrel M, Lof S, Al Sarireh B, Bjornsson B, Boggi U, Butturini G, Casadei R, De Pastena M, Esposito A, Fabre JM, Ferrari G, Fteriche FS, Fusai G, Koerkamp BG, Hackert T, D'Hondt M, Jah A, Keck T, Marino MV, Molenaar IQ, Pessaux P, Pietrabissa A, Rosso E, Sahakyan M, Soonawalla Z, Souche FR, White S, Zerbi A, Dokmak S, Edwin B, Hilal MA, Besselink M; European consortium on Minimally Invasive Pancreatic Surgery (E-MIPS). Short-term Outcomes After Spleen-preserving Minimally Invasive Distal Pancreatectomy With or Without Preservation of Splenic Vessels: A Pan-European Retrospective Study in High-volume Centers. Ann Surg. 2023 Jan 1;277(1):e119-e125. doi: 10.1097/SLA.0000000000004963. Epub 2021 Jun 2.
• Yongfei H, Javed AA, Burkhart R, Peters NA, Hasanain A, Weiss MJ, Wolfgang CL, He J. Geographical variation and trends in outcomes of laparoscopic spleen-preserving distal pancreatectomy with or without splenic vessel preservation: A meta-analysis. Int J Surg. 2017 Sep;45:47-55. doi: 10.1016/j.ijsu.2017.07.078. Epub 2017 Jul 21.
• Warshaw AL. Conservation of the spleen with distal pancreatectomy. Arch Surg. 1988 May;123(5):550-3. doi: 10.1001/archsurg.1988.01400290032004.
• Ferrone CR, Konstantinidis IT, Sahani DV, Wargo JA, Fernandez-del Castillo C, Warshaw AL. Twenty-three years of the Warshaw operation for distal pancreatectomy with preservation of the spleen. Ann Surg. 2011 Jun;253(6):1136-9. doi: 10.1097/SLA.0b013e318212c1e2.
• Granieri S, Bonomi A, Frassini S, Gjoni E, Germini A, Kersik A, Bracchetti G, Bruno F, Paleino S, Lomaglio L, Frontali A, Cotsoglou C. Kimura's vs Warshaw's technique for spleen preserving distal pancreatectomy: a systematic review and meta-analysis of high-quality studies. HPB (Oxford). 2023 Jun;25(6):614-624. doi: 10.1016/j.hpb.2023.02.009. Epub 2023 Mar 1.

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: November 20, 2023
• First Submitted That Met QC Criteria: December 4, 2023
• First Posted (Estimated): December 12, 2023

Study Record Updates

• Last Update Posted (Estimated): December 12, 2023
• Last Update Submitted That Met QC Criteria: December 4, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Prognosis; Pancreatic benign or low-grade malignant tumors; Minimally invasive spleen-preserving distal pancreatectomy; Kimura technique; Warshaw technique
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Pancreatic Diseases; Neoplasms; Pancreatic Neoplasms; Neuroendocrine Tumors
• Other Study ID Numbers: CSPAC-7

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No