Does Reinforcement of the Staple Line in Left Pancreatectomy Reduce the Rate of Pancreatic Fistula?

Pancreas Fistula After Distal Pancreatic Resection: Prevention and Treatment in a Randomized Controlled Trial

Dividing pancreas when performing left-sided resections opens the risk for leakage from the divided end of the pancreas. Pancreatic juices could have a severe effect on surrounding abdominal tissues with abscess formation producing systemic inflammation and potential lethal bleeding.

Studies have shown that reinforcement of the staple line when dividing pancreas could reduce the risk of leakage.

Surgisis (COOK Medical) a product already in use for staple line reinforcement in gastric and lung surgery could be used as a reinforcement when stapling pancreas in left sided resections.

In a prospective randomized trial we want to compare Surgisis reinforcement to no reinforcement of stapled division in left sided pancreatic resections.

Primary outcome is pancreatic fistula yes/no.

Study Overview

• Status: Unknown
• Conditions: Post Operative Pancreatic Fistula
• Intervention / Treatment: Device: Surgisis (C-SLRA-ECH60) made by COOK Medical

Detailed Description

Resection of the distal pancreas is often done due to a localized tumor in the body or tail of the pancreas. During later years the mortality after pancreatic resections have been reduced but there still is a substantial risk of severe complications mainly due to leakage from the pancreatic division line which could lead to suffering, longer hospital stay, higher costs and sometimes death. Leakage from a tail resection is probably more common than thought of before. Frequencies of above 30% and even up to 60% have been reported.

The use of somatostatin to reduce the production of pancreatic juice or comparison between stapled division, suturing of the remaining part of the cut pancreas or covering it with glue or available surrounding tissue have not showed significant superiority for any of these methods except for a positive trend regarding the stapling technique. Staple line reinforcement with resorbable mesh has in some studies showed a both negative and positive effect on pancreatic fistula frequency. These studies have been small and non-randomized. A larger randomized single blinded study by Hamilton et al on the other hand showed a significant positive effect on pancreatic fistula frequency after distal pancreatic resection using an absorbable reinforcement device put on the stapler, when only regarding type B and C fistulas as defined by the ISGPF (International Study Group on Pancreatic Fistula) pancreatic leak grading system.

Although all these endeavors the problem of pancreatic fistulas remain and therefore all these operations are concluded with the deposit of one or more drains to the area of the cut pancreas.

There is therefore of importance to continue the work of reducing complications in high risk pancreatic surgery using scientific procedures of high quality as in blinded randomized controlled trials (RCT). The use of reinforced stapling techniques has been used in lung surgery and bariatric surgery to reduce air leakage and strengthen anastomoses. The material used is processed submucosa from the small bowel of the pig, produced by COOK© Medical to fit endoscopic staplers from Ethicon© or Covidien©.

After the promising result from Hamilton et al we plan to study if the reinforcement made by COOK© could reduce the frequency of pancreatic fistula after stapled distal pancreatic surgery in a single blinded RCT.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: John Blomberg, MD, PhD; Email: john.blomberg@karolinska.se
• Study Contact Backup: Name: Marco Del Chiaro, MD, PhD; Email: marco.del.chiaro@ki.se

Study Locations

• Sweden
  • Stockholm, Sweden, SE-141 86
    • Recruiting
    • Dep of Surgical Gastroenterology, Karolinska University Hospital
    • Principal Investigator: John Blomberg, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Every patient eligible for pancreatic tail resection.

Exclusion Criteria:

• Not able to read Swedish.
• Not able to understand or accept the concept.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Surgisis reinforcement of staple line; The stapler used to divide the pancreas is reinforced with Surgisis (COOK Medical).	Device: Surgisis (C-SLRA-ECH60) made by COOK Medical; Surgisis is extracellular matrix collagen made of the submucosal layer of pigs intestines. Surgisis is gradually remodeled, leaving behind organized tissue; Other Names: Surgisis reinforcement of staple line
No Intervention: No reinforcement of staple line; The stapler used to divide the pancreas is not reinforced with any material

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post operative pancreatic fistula (POPF), Y/N	Pancreatic amylase concentration in any post operative drains. Fistula is diagnosed if pancreatic amylase > 3 times the upper normal limit of pancreatic amylase in plasma on post operative day 3 or later	Participants will be followed for the duration of hospital stay, an expected average of 2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality		< 90 days after the operation
POPF healing time	Time from diagnosis to healed pancreatic fistula	Participants will be followed for the duration of hospital stay, an expected average of 2 weeks
POPF grade according to International Study Group of Pancreatic Fistula (ISGPF) grade A/B/C	Worst POPF grade registered during the observation period.	Participants will be followed for the duration of hospital stay, an expected average of 2 weeks
Blood chemistry	During the first 7 post operative days each participant will have daily measurements taken from blood samples regarding C-reactive protein, white blood count, pancreatic plasma amylase and from drain fluid regarding pancreas amylase. The participants daily drain volume will also be measured.	The first 7 days after operation
Morbidity	According to Clavien scoring	Participants will be followed for the duration of hospital stay, an expected average of 2 weeks.
Hospital stay	Number of days	Participants will be followed for the duration of hospital stay, an expected average of 2 weeks.

Collaborators and Investigators

• Sponsor: Karolinska University Hospital
• Collaborators: University Hospital, Linkoeping; Lund University Hospital; Sahlgren´s University Hospital; Norrlands University Hospital
• Investigators: Principal Investigator: John Blomberg, MD, PhD, Dep of Surgical Gastoenterology, Karolinska University Hospital, Stockholm, Sweden

Publications and helpful links

General Publications

• Wennerblom J, Ateeb Z, Jonsson C, Bjornsson B, Tingstedt B, Williamsson C, Sandstrom P, Ansorge C, Blomberg J, Del Chiaro M. Reinforced versus standard stapler transection on postoperative pancreatic fistula in distal pancreatectomy: multicentre randomized clinical trial. Br J Surg. 2021 Apr 5;108(3):265-270. doi: 10.1093/bjs/znaa113.

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Anticipated): November 1, 2016
• Study Completion (Anticipated): December 1, 2016

Study Registration Dates

• First Submitted: May 21, 2014
• First Submitted That Met QC Criteria: May 23, 2014
• First Posted (Estimate): May 29, 2014

Study Record Updates

• Last Update Posted (Estimate): April 1, 2015
• Last Update Submitted That Met QC Criteria: March 31, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: Post operative pancreatic fistula; Left sided pancreatic resections; Distal pancreatic resections; Reinforced staple line
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathological Conditions, Anatomical; Pancreatic Diseases; Digestive System Fistula; Fistula; Pancreatic Fistula
• Other Study ID Numbers: Surgisis-001