Treatment of the Pancreatic Stump With Neoprene®-Based Glue After High-risk Pancreatoduodenectomy

Efficacy and Safety of Exocrine Pancreatectomy With Neoprene®-Based Glue After High-risk Pancreatoduodenectomy (PD) in Patients With Pancreatic, Papilla, Duodenal, and Distal Choledochus Neoplasm

The study evaluates the safety and efficacy of Neoprene-based glue in the management of pancreatic stump after pancreatoduodenectomy (PD) in patients at high risk for pancreatic fistula and early neoplastic recurrence, compared with a population of patients at conventional risk.

Study Overview

• Status: Completed
• Conditions: Postoperative Complications; Pancreatic Neoplasms; Pancreatic Fistula
• Intervention / Treatment: Procedure: Pancreatic duct occlusion with Neoprene; Procedure: Pancreato-Jejunal anastomosis

Detailed Description

Although improved in many aspects, the PD intervention is still burdened by a significant morbidity, related above all to the delicate phase following the removal of the tumor which involves the reconstruction of the gastro-enteric, biliary and especially pancreatic pathway. Among the many variants of the reconstructive phase, that of pancreato-jejunal anastomosis is the one burdened by the highest complication rate (quantified around 40%, with a percentage of pancreatic fistula between 5% and 35%).

In cases at risk of pancreatic fistula it is possible not to perform a conventional pancreato-jejunal anastomosis, but to decide to inject into the pancreatic stump the solidifying glues with the aim of inducing a chemical pancreatectomy of the exocrine component of the pancreas.

Neoprene® (Polychloroprene) has the property of polymerizing and solidifying in an environment with a pH lower than its own (pH <12).

After a systematic review of the sporadic experiences of chemical pancreatectomy published until today, due to the increased complexity of the surgical cases of patients undergoing PD, the investigators have undertaken a formal, single-center prospective study, aimed at clarifying the safety and efficacy data of a Neoprene®-based glue in patients selected through objective criteria (such as the high risk of pancreatic fistula and early tumor recovery after pancreatoduodenectomy).

In this study is expected the prospective collection of a cohort of patients with tumor of the head of the pancreas, papilla, duodenum and distal choledochus to undergo pancreatoduodenectomy (PD) at high risk of pancreatic fistula and / or local recurrence ("Study Arm").

At the same time a second cohort of patients with the same type of neoplasia will be collected, subjected to PD intervention in which however it will be possible to proceed with pancreato-jejunal anastomosis. This group will be defined as "Control Arm".

The first cohort will be the group of patients in which to detect the safety and efficacy of the treatment with Neoprene®-based glue.

The second cohort will be the comparative control group against which patients treated with Neoprene®-based glue can be compared in the hypothesis that peri-operative morbidity,mortality and short and long-term side effects of the intervention are equivalent.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Milano, Italy, 20133
    • Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with an alternative-Fistula Risk Score >15%.
• Patients with insulin-dependent diabetes.
• Cirrhotic patients or with histologically proven chronic liver disease.
• Age> 75 years (relative criterion, ie insufficient by itself to justify the procedure and therefore to be associated with one of the other cited criteria).
• Patients with intraoperative demonstration on histological examination of lymph node metastasis;
• Patients with R1 interventions.
• Presence of minimal extra-pancreatic tumor disease not detected pre-operatively (nodule of carcinosis, single liver metastasis) and removed with the primary tumor within the same intervention;
• Patients undergoing preoperative radiotherapy / chemotherapy for tumors reconverted to surgical operability.

Exclusion Criteria:

• All other patients who undergo PD in which the eligibility conditions for the study group are not present, are enrolled in the Control Arm..

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Pancreatic duct occlusion; Patients considered at high risk for pancreatic fistula or oncological relapse due to introperative evaluation submitted to pancreatic duct occlusion with Neoprene-based glue.	Procedure: Pancreatic duct occlusion with Neoprene; Pancreatic duct occlusion of the pancreatic stump with Neoprene-based glue after Pancreatoduodenectomy.
ACTIVE_COMPARATOR: Pancreato-Jejunal anastomosi; Patients considered at low risk for pancreatic fistula submitted to pancreato-jejunal anastomosis.	Procedure: Pancreato-Jejunal anastomosis; Standardized pancreato-jejunal anastomosis after Pancreatoduodenectomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of postoperative complications of grade > II according to Dindo-Clavien classification	Comparison of 90-days clinically relevant postoperative morbidity rate of grade > II according to Dindo-Clavien classification between the two arms.	90 days
Rate of overall postoperative complications	Comparison of 90-days overall postoperative morbidity rate of any grade according to Dindo-Clavien classification between the two arms.	90 days
Rate of postoperative mortality	Comparison of 90-days postoperative mortality rate between the two arms	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with onset of post-surgical diabetes	Comparison between arms of onset of newly diagnosed post-surgical diabetes needing tablets or insulin therapy during a follow-up period of 12 months	12 months
Percentual variation of weight after pancreatoduodenectomy	Comparison between arms of percentual weight variation between preoperative measure in kilograms and follow up at 1, 3, 6 and 12 months	12 months
Variation of Body Mass Index after pancreatoduodenectomy	Comparison between arms of Body Mass Index variation measured combining weight and height to report BMI in kg/m^2 between preoperative evaluation and follow up at 1, 3, 6 and 12 months	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Evaluation of overall survival in both arms of study	36 months

Collaborators and Investigators

• Sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Publications and helpful links

General Publications

• Mazzaferro V, Virdis M, Sposito C, Cotsoglou C, Droz Dit Busset M, Bongini M, Flores M, Prinzi N, Coppa J. Permanent Pancreatic Duct Occlusion With Neoprene-based Glue Injection After Pancreatoduodenectomy at High Risk of Pancreatic Fistula: A Prospective Clinical Study. Ann Surg. 2019 Nov;270(5):791-798. doi: 10.1097/SLA.0000000000003514.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2015
• Primary Completion (ACTUAL): January 1, 2019
• Study Completion (ACTUAL): January 1, 2019

Study Registration Dates

• First Submitted: November 5, 2018
• First Submitted That Met QC Criteria: November 8, 2018
• First Posted (ACTUAL): November 13, 2018

Study Record Updates

• Last Update Posted (ACTUAL): October 5, 2021
• Last Update Submitted That Met QC Criteria: October 4, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pathological Conditions, Anatomical; Pancreatic Diseases; Digestive System Fistula; Neoplasms; Fistula; Pancreatic Neoplasms; Postoperative Complications; Pancreatic Fistula
• Other Study ID Numbers: 191/14

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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