A Randomized Trial of Two Surgical Techniques for Pancreaticojejunostomy in Patients Undergoing Pancreaticoduodenectomy
Biliary Tract Neoplasms
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Randomized Trial of Two Surgical Techniques for Pancreaticojejunostomy in Patients Undergoing Pancreaticoduodenectomy|
- The primary endpoint will be the pancreatic fistula rate.
- length of hospitalization
- percutaneous intervention rates
- reoperation rates
|Study Start Date:||July 2006|
|Estimated Study Completion Date:||December 2015|
|Estimated Primary Completion Date:||July 2015 (Final data collection date for primary outcome measure)|
Pancreaticoduodenectomy (PD) is a commonly performed operative procedure which is used in selected patients with benign and malignant diseases of the pancreas and periampullary region. The procedure involves regional resection of the pancreatic head, neck, and uncinate process en-bloc with the duodenum, distal bile duct, and lymph nodes. The standard 'Whipple' operation also adds a distal gastrectomy to the above procedures, while a pylorus-preserving pancreaticoduodenectomy (PPPD) spares the distal stomach. The indications for PD include neoplastic processes confined to the periampullary region, such as pancreatic cancer, distal common bile duct cancer, duodenal cancer, ampullary cancer, neuroendocrine tumors, cystic tumors, etc. A small number of benign conditions, such as chronic pancreatitis and benign neoplasms are also treated with PD. Upon completion of the pancreatic resection, 3 anastomoses are used to re-establish GI continuity—a pancreatic-enteric anastomosis, a biliary-enteric anastomosis, and a gastro or duodeno-enteric anastomosis. The pancreatic-enteric anastomosis has traditionally been the most troubling of these anastomoses because of a failure to heal and resultant fistulas and leaks.
The operative mortality rate for PD is usually less than 5% in major surgical centers with significant experience with the procedure. The leading causes of mortality include hemorrhage, cardiac events, and sepsis (often related to a pancreatic-enteric fistula). In contrast to this low mortality rate, the morbidity rate is still quite high with one review showing a rate of 40%. One of the most common causes of morbidity is a leak or pancreatic fistula from the pancreatic-enteric anastomosis. A recent review estimated the incidence of this complication to be 10% to 28.5%. A pancreatic fistula is currently defined by the International Study Group for Pancreatic Fistulas (ISGPF) as drain amylase levels that are ≥3 times normal amylase levels from the third postoperative day onward, if drain output is ≥ 10ml, and if the color of the drained fluid is altered (non-serous). Several large single institution series from the Mannheim, Lahey, and Mayo Clinics have shown leak rates of 11-15%. The Mannheim Clinic series demonstrated that 20% of the pancreatic fistulas were directly responsible for postoperative deaths.
There have been several randomized prospective trials by investigators at the Johns Hopkins Hospital which have tested various interventions attempting to improve the leakage rates. In one trial, they determined that leak rates were similar (11-12%) whether the pancreatic-enteric anastomosis was a pancreaticojejunostomy (PJ) or a pancreaticogastrostomy (PG). In another trial, these investigators evaluated the use of prophylactic octreotide as an agent to reduce pancreatic fistula rates—in this study there was no decrease in fistula rates with the use of octreotide. Finally, these authors most recently performed a randomized, prospective trial of stenting the pancreatic-enteric anastomosis. In this trial, the fistula rates were not changed by the placement of a perioperative stent across the anastomosis.
There are two widely used methods for the PJ reconstruction after PD—invagination or 'dunking' the pancreatic remnant or end-to-side duct-to-mucosa PJ. In the invagination technique, the cut end of the pancreas in sewn into an opening in the side of the jejunum using two layers of suture—an outer layer of permanent suture on the pancreas capsule and bowel serosa and muscle, and an inner layer of running dissolvable suture on the duct and pancreatic parenchyma and full thickness of the bowel wall. In the duct-to-mucosa technique, there is again an outer layer of interrupted permanent suture. However, the inner layer is an interrupted anastomosis between the pancreatic duct and the bowel mucosa. In one single institution study utilizing the duct-to-mucosa technique and an internal stent, Strasberg et al demonstrated a pancreatic fistula rate of 1.6% in 123 patients. In another review by Tani et al, the fistula rate was 11% for the stented duct-to-mucosa technique and 6.5% for the 2 layer end-to-side externally stented technique.
There has been only one small randomized, prospective trial evaluating a duct-to-mucosa versus an end-to-side PJ reported in the literature. In this trial, the authors randomized 144 patients undergoing PD to either a 2-layer duct-to-mucosa anastomosis or a single layer end-to-side anastomosis which was not invaginated. Pancreatic fistulas were seen in 14% of patients—13% in the duct-to-mucosa group and 15% in the end-to-side group and there was no difference in complications between groups. It is not entirely clear from this study how these anastomoses were performed, but it does not appear that their construction was compatible to the methods that are most commonly used today.
Therefore, we propose to perform a randomized, prospective, controlled study comparing these two techniques. This study will be offered to all patients at Thomas Jefferson Hospital undergoing PD. Patients will be recruited on the basis of the preoperative anticipation of pancreaticoduodenal resection and preoperative consent will be obtained. Stratification and randomization will be performed intraoperatively, following pancreaticoduodenal resection. Because many studies have demonstrated that leak rates are directly related to pancreatic texture, we will stratify into two groups: soft (normal) texture (predicted fistula rate of 15-30%) and hard (fibrotic) texture (predicted fistula rate of 0-15%). Patients will be randomized to one of two groups: 1) pancreatic duct to jejunal mucosa, two-layer anastomosis or 2) end-to-side, two-layer, invagination technique.
The intraoperative management of the patients will not be influenced by this study and will be under the direction of the attending surgeon. The perioperative care of the patient, including the use of prophylactic antibiotics, gastric acid secretory inhibition agents, nasogastric tubes, the timing of removal of operatively placed closed-suction drains, and the restoration of oral intake will remain under the direction of the attending surgeon. If a postoperative pancreatic fistula does occur, the attending surgeon will manage the fistula appropriately. We have a Critical Pathway in place which we will use to standardize patient care and insure uniform postoperative management.
Immediately following the PD, the attending surgeon will complete a short questionnaire documenting the type of resection performed, the type of anastomosis, the character of the remnant pancreas, the size of the pancreatic duct, how the pancreas was transected (stapler, electrocautery, etc), and other details of the operative procedure. Other routine data that will be collected includes further details of the operative procedure (from the operative report), pathology of the resected specimen (from the pathology report), and occurrence of postoperative morbidity and mortality.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00359320
|Contact: Adam C Berger, MDfirstname.lastname@example.org|
|United States, Pennsylvania|
|Thomas Jefferson University Hospital||Recruiting|
|Philadelphia, Pennsylvania, United States, 19107|
|Sub-Investigator: Charles Yeo, MD|
|Sub-Investigator: Eugene P Kennedy, MD|
|Sub-Investigator: Ernest Rosato, MD|
|Sub-Investigator: Karen Chojnacki, MD|
|Sub-Investigator: Cataldo Doria, MD|
|Sub-Investigator: Bernadette Profeta, MD|
|Sub-Investigator: Patricia Sauter, CRNP|
|Principal Investigator:||Adam C Berger, MD||Thomas Jefferson University|