Ignite Creation Date:
2024-05-05 @ 4:57 PM
Last Modification Date:
2024-10-26 @ 9:26 AM
Study NCT ID:
NCT00359320
Status:
TERMINATED
Last Update Posted:
2018-06-13
First Post:
2006-08-01
Brief Title:
A Randomized Trial of Two Surgical Techniques for Pancreaticojejunostomy in Patients Undergoing Pancreaticoduodenectomy
Sponsor:
Thomas Jefferson University
Organization:
Thomas Jefferson University
Study Overview
Official Title:
A Randomized Trial of Two Surgical Techniques for Pancreaticojejunostomy in Patients Undergoing Pancreaticoduodenectomy
Status:
TERMINATED
Status Verified Date:
2018-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Terminated by IRB
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of this trial is to determine whether a mucosa-to-mucosa technique of pancreaticojejunostomy will improve the pancreatic fistula rate
Detailed Description:
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 285 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 16 in 123 patients In another review by Tani et al the fistula rate was 11 for the stented duct-to-mucosa technique and 65 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
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 285 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 16 in 123 patients In another review by Tani et al the fistula rate was 11 for the stented duct-to-mucosa technique and 65 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None