Islet Autotransplantation in Patients at Very High-risk Pancreatic Anastomosis

NCT ID: NCT01346098

Last Updated: 2020-11-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-07-31
• Study Completion Date: 2019-04-30

Brief Summary

The goal of the proposal is to demonstrate that, in patients with disease of the pancreatic head with very high-risk of complications of pancreatojejunal reconstruction (soft pancreas and pancreatic duct diameter <3 mm), total pancreatectomy with islet autotransplantation (IAT) is associated with a lower morbidity (in terms of surgical or medical complications) and mortality compared with pancreaticoduodenectomy and pancreatojejunal anastomosis.

Detailed Description

Complications of the pancreatic anastomosis still represents a significant risk for death after the resection of the pancreatic head. In an effort to decrease morbidity and mortality, the referral of patients who need a pancreaticoduodenectomy to institutions (and surgeons) performing a high volume of this surgical procedure has been championed. Nonetheless, the role of prophylactic medications and the best surgical technique(s) for the removal of the pancreatic head are still debated. However, very few prospective randomized clinical trials have been conducted to compare different surgical techniques.

Our study will address for the first time the role for preemptive total pancreatectomy and IAT in selected patients undergoing pancreaticoduodenectomy that are considered high risk for pancreaticojejunostomy disruption (eg, small pancreatic duct, soft pancreas). The information expected is the identification of total pancreatectomy and the IAT as the standard treatment in a subgroup of patient with pathologies of the pancreatic head at high risk for leakage of pancreatic anastomosis. Ultimately this project will lead to reserve more innovative cell therapy for patients with the highest risk of anastomosis failure reducing pancreatojejunal reconstruction related morbidity and mortality

Conditions

Postpancreatectomy Hyperglycemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

GROUP B

At the time of surgery the surgeon will directly assess pancreatic consistency and the pancreatic duct size. In the presence of a soft pancreas and a small duct (diameter \<3 mm), the patient will be randomly assigned to receive either a pancreaticoduodenectomy with pancreatic anastomosis (group A) or a total pancreatectomy with IAT (group B).

Group Type: EXPERIMENTAL

Total pancreatectomy with islet autotransplantation

Intervention Type: PROCEDURE

If the patient will be assigned to this group, the surgeon will complete the pancreatectomy preserving the spleen. The body and tail of the pancreas will be sent to the islet isolation facility. Islets will be isolated and purified according to the automated method described by Ricordi. The resulting islet tissue will be suspended in a cold isotonic saline solution and infused into the portal vein during the next 24h.

GROUP A

Group Type: ACTIVE_COMPARATOR

Pancreaticoduodenectomy with pancreatic anastomosis

Intervention Type: PROCEDURE

Standard lymphadenectomy, end-to-side two-layer pancreaticojejunostomy and duodenojejunostomy will be performed. If the pylorus is preserved, so will be the right gastric artery, unless the artery is damaged or hindering adequate gastric mobilization. No prokinetic agent will be administered routinely, but IV metoclopramide will given on demand (10 mg , three times daily). Prophylaxis will consist of octreotide (0,1 mg three times daily from day 0 to 7), low molecular weight heparin and a single dose of antibiotic (cefazolin 2 g). Early postoperative analgesia will be achieved by epidural or, when contraindicated, patient-controlled analgesia

Interventions

Pancreaticoduodenectomy with pancreatic anastomosis

Standard lymphadenectomy, end-to-side two-layer pancreaticojejunostomy and duodenojejunostomy will be performed. If the pylorus is preserved, so will be the right gastric artery, unless the artery is damaged or hindering adequate gastric mobilization. No prokinetic agent will be administered routinely, but IV metoclopramide will given on demand (10 mg , three times daily). Prophylaxis will consist of octreotide (0,1 mg three times daily from day 0 to 7), low molecular weight heparin and a single dose of antibiotic (cefazolin 2 g). Early postoperative analgesia will be achieved by epidural or, when contraindicated, patient-controlled analgesia

Intervention Type: PROCEDURE

Total pancreatectomy with islet autotransplantation

If the patient will be assigned to this group, the surgeon will complete the pancreatectomy preserving the spleen. The body and tail of the pancreas will be sent to the islet isolation facility. Islets will be isolated and purified according to the automated method described by Ricordi. The resulting islet tissue will be suspended in a cold isotonic saline solution and infused into the portal vein during the next 24h.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Patients >18 years of age
• Ability to provide written informed consent
• Mentally stable and able to comply with the procedures of the study protocol
• Fasting glycaemia <126 mg/dl without glucose-lowering medications.

Exclusion Criteria

• Any medical condition that, in the opinion of the investigator, will interfere with the safe completion of the trial
• Diagnosis of intraductal papillary mucinous cancer, unless the absence of multifocal lesion is demonstrated by endoscopic US
• Presence of multifocal or residual disease at the pancreatic margin.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ministry of education, university and research, Italy

UNKNOWN

Sponsor Role: collaborator

Ospedale San Raffaele

OTHER

Sponsor Role: lead

Responsible Party

Piemonti Lorenzo

Director Islet Transplantation Program

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Lorenzo Piemonti, MD

Role: PRINCIPAL_INVESTIGATOR

Fondazione Centro San Raffaele del Monte Tabor

Gianpaolo Balzano, MD

Role: STUDY_DIRECTOR

Fondazione Centro San Raffaele del Monte Tabor

Locations

IRCCS San Raffaele

Milan, , Italy

Countries

Italy

References

Balzano G, Zerbi A, Aleotti F, Capretti G, Melzi R, Pecorelli N, Mercalli A, Nano R, Magistretti P, Gavazzi F, De Cobelli F, Poretti D, Scavini M, Molinari C, Partelli S, Crippa S, Maffi P, Falconi M, Piemonti L. Total Pancreatectomy With Islet Autotransplantation as an Alternative to High-risk Pancreatojejunostomy After Pancreaticoduodenectomy: A Prospective Randomized Trial. Ann Surg. 2023 Jun 1;277(6):894-903. doi: 10.1097/SLA.0000000000005713. Epub 2022 Sep 30.

Reference Type: DERIVED

PMID: 36177837 (View on PubMed)

Other Identifiers

PAN-IT

Identifier Type: -

Identifier Source: org_study_id