PAN-IT: Islet Autotransplantation in Patients at Very High-risk Pancreatic Anastomosis

Sponsor

Ospedale San Raffaele (Other)

Overall Status

Completed

CT.gov ID

NCT01346098

Collaborator

Ministry of education, university and research, Italy (Other)

Enrollment

Location

Arms

105

Actual Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Postpancreatectomy Hyperglycemia	Procedure: Pancreaticoduodenectomy with pancreatic anastomosis Procedure: Total pancreatectomy with islet autotransplantation	Phase 2

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

Study Design

Study Type:

Interventional

Actual Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Total Pancreatectomy With Islet Autotransplantation as a Superior Alternative to Pancreatoduodenectomy in Patients at Very High-risk of Complications of the Pancreatic Anastomosis: a Single-center Prospective Randomised Clinical Trial

Actual Study Start Date :

Jul 1, 2010

Actual Primary Completion Date :

Dec 1, 2018

Actual Study Completion Date :

Apr 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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).	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.
Active Comparator: GROUP A	Procedure: 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

Arm

Intervention/Treatment

Experimental: 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).

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.

Active Comparator: GROUP A

Procedure: 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

Outcome Measures

Primary Outcome Measures

incidence of complications after pancreatic surgery [90 days from discharge]
Complications will be defined and graded according to the Novel Grading System classification ( DeOliveira et al 2006). A special emphasis is given to life-threatening and permanently disabling complications.

Secondary Outcome Measures

Incidence of each individual postoperative complication [90 days from discharge]
death pancreatic fistula defined according to the International Study Group on Pancreatic Fistula (Bassi C et al 2005) delayed gastric emptying (DGE) defined according to the International Study Group on Pancreatic Fistula (Wente et al 2007) intra-abdominal complications medical complications
Incidence of endocrine and exocrine pancreatic insufficiency [12 months after surgery.]
We will assess endocrine pancreatic function by measuring fasting plasma glucose and HbA1c in all patients. Clinical hallmarks of pancreatic exocrine insufficiency include symptoms of fat malabsorption, such as steatorrhea, weight loss and abdominal pain. Frequency of bowel movements and characteristics of stools will be serially recorded. Fat-soluble vitamins such as A, D, E and K will be measured 12 month after the hospital discharge after the index surgery. Oral pancreatic enzyme supplementation will be prescribed according to the severity of clinical steatorrhea and weight loss.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	IRCCS San Raffaele	Milan		Italy	20132

Sponsors and Collaborators

Ospedale San Raffaele
Ministry of education, university and research, Italy

Investigators

Principal Investigator: Lorenzo Piemonti, MD, Fondazione Centro San Raffaele del Monte Tabor
Study Director: Gianpaolo Balzano, MD, Fondazione Centro San Raffaele del Monte Tabor