Technical Strategies for Pancreatic Fistula Prevention After Pancreaticoduodenectomy in High-risk Pancreatic Remnant

Study Overview
=================
Brief Summary
-----------------
This trial will investigate what surgical technique between pancreaticogastrostomy and pancreaticojejunostomy with transanastomotic externalized drains is associated with the lowest rate of pancreatic fistula after pancreaticoduodenectomy in case of high-risk pancreatic remnants.

Detailed Description
-----------------
Pancreatic fistula is the major determinant of outcome after pancreaticoduodenectomy. Several strategies to reduce the burden of this complication have been proposed in the last decade. A definite answer about what is the best technique to approach a high-risk pancreatic stump is still needed. Both pancreaticogastrostomy and pancreaticojejunostomy with transanastomotic externalized drains have been proposed in this setting, but often studies do not provide a reliable risk stratification and result are extremely variable. The aim of this trial is to evaluate what surgical technique, between pancreaticogastrostomy and pancreaticojejunostomy with transanastomotic externalized drains, is associated with the lowest rate of pancreatic fistula in case of high-risk pancreatic remnants. Risk stratification will be provided through the Fistula Risk Score, a clinical risk score that has been extensively validated.

Official Title
-----------------
Technical Strategies for Pancreatic Fistula Prevention After Pancreaticoduodenectomy in High-risk Pancreatic Remnant: a Risk-adjusted Randomized Controlled Trial

Conditions
-----------------
Pancreatic Fistula

Intervention / Treatment
-----------------
* Procedure: Pancreaticogastrostomy with external drain
* Procedure: Pancreaticojejunostomy with transanastomotic drain


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: All the patients undergoing pancreaticoduodenectomy (only Whipple or Traverso) for all kind of pancreatic disease (benign, malignant or premalignant). Patients able to give their informed consent Exclusion criteria Informed consent withdrawal Impossibility to undergo surgery for any reason Use of glues or biological matrices to protect the anastomosis Fistula Risk Score < 7 Post-operative octreotide analogues administration (only prophylactic use, therapeutic use allowed) Wrong randomization

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Pancreaticogastrostomy<br>Pancreaticogastrostomy with external drain | Procedure: Pancreaticogastrostomy with external drain<br>* Pancreatico-enteric anastomosis is provided according to the Bassi technique, pancreatic remnant is pushed into the gastric cavity through a posterior gastrotomy. An externalized drain is placed into the main pancreatic duct.<br>|
| Active Comparator: Pancreaticojejunostomy<br>Pancreaticojejunostomy with transanastomotic drain | Procedure: Pancreaticojejunostomy with transanastomotic drain<br>* Pancreatico-enteric anastomosis is provided through a double-layer, duct-to-mucosa anastomosis with a transanastomotic externalized drain.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post-operative Pancreatic Fistula (POPF) | Presence of Amylase > 3 times the upper limit of normal in surgical drains at or by post-operative day 3 (POD) determining a clinically relevant change in patient's management | 30 days post-operative | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| POPF severity | POPF grade B and grade C rates | 30 days post-operative | 
| Length of Hospital Stay | calculated from the day of surgery to the day of discharge, adding up the days after a possible re-admission | 1 year | 
| Mortality | Death related to surgical morbidity | 90 days | 
| Post-Pancreatectomy Hemorrhage | As defined by the International Study Group for Pancreatic Surgery (ISGPS), grade A, B and C rates | 90 days | 
| Delayed Gastric Emptying | As defined by ISGPS, grade A, B and C rates | 90 days | 
| Biliary fistula | Output of bile from drains on or by POD 3, pancreaticojejunostomy leak should be ruled out | 90 days | 
| Gastrojejunal/Duodenojejunal fistula | Fistula from gastro/duodenojejunostomy | 90 days | 
| Abdominal abscess | Collection >5cm in size, containing gas bubbles, determining systemic signs of infection | 90 days | 
| Acute pancreatitis | Altered serum amylase count on POD 0 or POD 1 | 1 day post index surgery | 
| Wound infection | Superficial and Deep Surgical Site Incisional Infection as defined by the Center for Disease Control and Prevention | 90 days | 
| Blood transfusions | Need and number of packed red blood cells transfused | 90 days | 
| Myocardial infarction | Myocardial necrosis | 90 days | 
| Acute Kidney Failure | Abrupt change in serum creatinine >1.5 baseline value | 90 days | 
| Pulmonary Embolism | Blood clots in the pulmonary arterial system | 90 days | 
| Pneumonia | Bacterial infection of the lungs | 90 days | 
| Respiratory insufficiency | Need for re-intubation | 90 days | 
| Urinary Tract Infection | Bacterial infection of the urinary tract | 90 days | 
| Cerebrovascular accidents | Stroke, hemorrhage, brain death | 90 days | 
| Reoperation | Need for new surgery due to severe morbidity | 90 days | 
| Readmission | New admission within 30-days of discharge from hospital | 30 days after hospital discharge | 
| Time-to-adjuvant therapy | Time form index operation to the beginning of adjuvant treatment (only for malignancy) | 1 year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Pancreaticoduodenectomy, Pancreaticogastrostomy, Pancreaticojejunostomy, Stent, Transanastomotic drain