Clinical Trial Details
— Status: Withdrawn
Administrative data
| NCT number |
NCT01913275 |
| Other study ID # |
GIS/2/2001 |
| Secondary ID |
|
| Status |
Withdrawn |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
March 2006 |
| Est. completion date |
February 2014 |
Study information
| Verified date |
January 2024 |
| Source |
All India Institute of Medical Sciences, New Delhi |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Periampullary carcinoma and carcinoma head of pancreas are common causes of obstruction at
the lower end of the common bile duct. Whenever possible, surgical resection in the form of
Whipple Pancreaticoduodenectomy (WPD) is the treatment of choice. However, this operation is
associated with a substantial postoperative morbidity and mortality. With advances in
surgical techniques and postoperative care there has been a decrease in the operative
mortality. However, the postoperative morbidity remains high varying between 5%-64%. Of the
various risk factors, the degree of jaundice as indicated by the serum bilirubin levels has
been associated with an increased risk of complications. Preoperative biliary drainage has
been tried to decrease the serum bilirubin levels and consequently decrease postoperative
morbidity and mortality. Internal biliary drainage can be achieved by surgical
cholecystojejunostomy or endoscopic bile duct stenting. Endoscopic stenting can be done as a
day care procedure under conscious sedation, but involves insertion of a foreign body
(stent), which results in introduction of bacteria into the bile and problems of
postoperative infection. Also, endoscopic stenting before surgery may result in difficulty in
dissecting around the common bile duct during the surgical procedure. While the surgical
bilioenteric bypass has the advantage that no foreign body is inserted into the biliary tree
and hence the likelihood of sepsis is low, it requires anesthesia and involves a surgical
incision.
There is no study comparing the outcomes of preoperative endoscopic and surgical drainage in
patients undergoing pancraticoduodenectomy. We plan to compare the outcomes of preoperative
endoscopic biliary drainage with surgical drainage in patients undergoing
pancreaticoduodenectomy.
Description:
Hypothesis preoperative biliary decompression by Cholecystojejunostomy will reduce infective
complication by 23% as compared to endocopic stenting INTRODUCTION Pancreaticoduodenectomy
has been associated with a substantial postoperative morbidity and mortality. Advances in
surgical techniques and postoperative care have led to a decrease in the operative mortality.
However, the postoperative morbidity has remained high varying between 5%-64%.1 Of the
various risk factors, analyzed in the retrospective studies, the degree of jaundice as
indicated by the serum bilirubin levels has been associated with an increased risk of
complications.2-5 Preoperative biliary drainage has been tried to decrease the serum
bilirubin levels and consequently decrease postoperative morbidity and mortality. However,
its role remains controversial.
External biliary drainage using percutaneous transhepatic insertion of a catheter has been
used.6,7 The disadvantages of external bleary drainage include the risk of spontaneous
catheter dislodgement, inflammation and pain at the puncture site, leak of ascitic fluid and
bile around the catheter, and loss of fluid and electrolytes. Moreover, bile has an
antibacterial action and its loss has been associated with sepsis and renal failure. Hence,
internal biliary drainage is considered more appropriate.
Internal biliary drainage can be achieved by surgical cholecystojejunostomy or endoscopic
bile duct stenting. The internal drainage provides a more physiological route for drainage of
bile into duodenum or jejunum, which prevents any loss of electrolytes and bile salts, and
reduces the risk of endotoxemia. Two studies using endoscopic bilary drainage have shown
benefit in terms of reduced postoperative morbidity and mortality.7,8 However, it involves
the insertion of a foreign body (stent), which results in occurrence of bacteria in bile with
its attendant problems of postoperative sepsis.
Prior to the availability of the endoscopic and percutaneous methods, surgical bilioenteric
bypass was the only method for preoperative biliary decompression. The disadvantage of this
method is that it requires anesthesia and involves a surgical incision. However, its
advantages are that no foreign body is inserted into the biliary tree and hence the
likelihood of sepsis is low. Also, endoscopic stenting before pancreaticoduodenectomy may
result in difficulty while dissecting the common bile duct. Historically, Whipple conceived
pancreaticoduodenectomy as a two staged procedure. The first stage was surgical decompression
of biliary tract to reduce the level of the hyperbilirubinemia to minimize mortality and
morbidity after extirepative surgery and the second stage was a definitive surgical
resection.
There is no study comparing the outcomes of preoperative endoscopic and surgical drainage in
patients undergoing pancraticoduodenectomy. We plan to carry out a randomized trial comparing
the outcomes of preoperative endoscopic biliary drainage with surgical drainage in patients
undergoing pancraticoduodenectomy.
AIMS AND OBJECTIVES
To compare endoscopic bilary stenting with cholecystojejunostomy as a preoperative biliary
drainage procedure in patients undergoing pancreaticoduodenectomy with respect to
1. Technical success
2. Successful drainage
3. Procedural-related complications
4. Hospital stay
5. Intra-operative difficulty
6. Postoperative morbidity and mortality.
PATIENTS AND METHODS
All consecutive patients with surgical obstructive jaundice attending Gastrointestinal
surgery and medicine OPD at AIIMS will be evaluated with a detailed history and clinical
examination, liver function tests and an ultrasound abdomen. Those patients who have liver
function tests and an ultrasound suggestive of lower end block will be further evaluated with
a contrast enhanced CT and side viewing endoscopy (biopsy whenever possible) to characterize
the nature of block.
Inclusion criteria
1. Patients with periampullary carcinoma and carcinoma of the head of pancreas.
2. Patients with serum bilirubin >15mg/dl
Exclusion criteria
1. Patients with gastric outlet obstruction.
2. Patients with unresectable tumour assessed by imaging techniques.
3. Patients with a history of cholecystectomy and Billroth II gastrectomy.
4. Patients stented outside Study design the number of patients to be included was
calculated to be 67 in each group based on assumption that infective complications will
be reduced to 7%. the sample size was calculated with power of 90% and alpha error of
0.5 Patients will be randomly divided using sealed envelope method (using computer
generated random numbers) to two groups of 50patients each.
Group A: Endoscopic stenting Group B: Cholecystojejunostomy
Preprocedural preparation10
1. Informed consent: The patient will be explained about the course and nature of disease,
alternatives methods of treatment available, outcome with and without treatment. The
procedure will be explained completely to the patient including the risks and
complications involved and then consent will be taken.
2. Investigations The following investigations will be done in all the patients
1. Prothrombin time
2. Liver function tests (LFTs)
3. Baseline haematological, biochemical and radiological investigations done in all
patients as follows:
i) Haemogram ii) Kidney Function Test iii) Electrolytes iv) Blood sugar v) Chest X-ray
vi) ECG
3. Prophylactic antibiotics: All patients will receive prophylactic antibiotics (Inj
cefaperazone + sulbactam 1 gm) 2 hours before the procedure and these will be continued
upto 72 hours after the procedure. Patients will be kept nil orally for 8 hours prior to
the procedure, and will be well hydrated with i.v. fluids.
Procedure
1. Endoscopic stenting (EBS)11 A therapeutic duodenoscope and a standard sphincterotome
will be used for canulation of the bile duct. A hydrophilic guidewire (Terumo, 0.032"
dia or Jag wire 0.035" dia, microvasive) will be used to cross the malignant stricture.
After the stricture was crossed with the help of a guidewire, the wire will be removed
and bile will be aspirated. A small sphincterotomy will be done with a wire-guided
sphincterotome to facilitate the passage of the stent. The sphincterotome will be
removed and a guide catheter will be passed over the guidewire and then a 10 F 7 cm long
straight plastic stent will be inserted across the stricture over the guidewire. A
maximum of three attempts will be allowed for insertion of the stent after which it will
be categorized as procedural failure.
2. Cholecystojejunostomy (CJ) Cholecystojejunostomy will be done under local anesthesia
using a small subcostal incision made over the distended gall bladder. The anastomosis
will be done in 2 layers using 3-0 vicryl and 3-0 silk sutures.
Any complications related to both procedures and following them will be recorded.
Follow up On day 5 following the endoscopic or surgical bypass, the patients will be
reassessed clinically and with hematological and biochemical parameters with special
reference to haemogram and LFTs to know whether the biliary drainage is effective. After 4
weeks along with clinical, hematological and biochemical parameters, nutritional parameters
will also be assessed.
All patients will be considered for definitive procedure at least after 4 weeks after the
biliary drainage procedure.
The operative difficulty, amount of blood loss, number of transfusions required and operative
time during definitive surgery will be recorded. Following pancreaticoduodenectomy, the
postoperative complications will be evaluated in both groups.
Outcome measures Primary
1. Technical success: Passage of a stent across the stricture, along with flow of bile
through the stent.
2. Successful drainage: A decrease in bilirubin of at least 20% of the pretreatment value
within 5 days after procedure
3. Procedure-related complication: was defined complications directly related to stent
insertion/CJ
4. Intraoperative assessment: The operative difficulty, amount of blood loss, number of
transfusions required and operative time during definitive surgery.
Secondary
1. Procedure-related mortality: was defined as death directly related to complications of
stent insertion/CJ
2. Duration of hospital stay: Number of days in hospital from the time of surgery or
stenting to initial discharge.
3. Postoperative complication: Complications occurring within 30 days after
pancreaticoduodenectomy
1. Wound infection: presence of purulent discharge with or without growth of
microorganism or serous discharge that grows a pathogenic microorganism.
2. Intra-abdominal abscess: when pus was drained, aspirated or discharged from the
peritoneal cavity
3. Postoperative haemorrhage: Hematemesis, malena, blood los from the abdominal wound
or drian site requiring 2 or more units of blood transfusion.
4. Pancreaticojejunal leak: Drain fluid amaylase level > 3 times the serum amylase on
postoperative day 3 or beyond or percutaneous drainage of amylase rich
intra-abdominal collection, with or without clinical sequelae such as fever,
leucocytosis, fistula or abscess.
5. Bile leak: Clinical bile leak or elevated bilirubin level in drain fluid with
normal serum level.
4. Postoperative mortality: was defined as death within 30 days after surgery or before
discharge from the hospital.
Stastistical analysis Baseline characteristic will be expressed in mean (SD). The Pearson chi
square test and Fischer exact test will be used for to compare the categorical data as
appropriate. The Student t-test will be used to compare the continuous variables.
Multivariate analysis will be done using logistic regression tests. Length of hospital stay
will be compared using the log-rank test and the Wilcoxon signed rank test. A pvalue of <0.05
will be taken as significant.
REFERENCES
1. Sastry RA, Sivam S. Routine preoperative biliary drainage of biliary tree must not be
done in patients with obstructive jaundice. Debates in gastrointestinal surgery.
Jabalpur- banarsidas Bhanot publishers. 1998:115-62
2. Povoski SP, Karpeh MS Jr, Conlon KC, Blumgart LH, Brennan MF. Association of
preoperative biliary drainage with postoperative outcome following
pancreaticoduodenectomy. Ann Surg 1999;230:131-42.
3. Grace PA, Pitt HA, Tompkins RK, DenBesten L, Longmire WP Jr. Decreased morbidity and
mortality after pancreatoduodenectomy. Am J Surg 1986;151:141-9.
4. Kairaluoma MI, Stahlberg M, Kiviniemi H, Haukipuro K. Results of pancreatoduodenectomy
for carcinoma of the head of the pancreas. Hepatogastroenterology 1989;36:412-8.
5. Blenkharn JI, Benjamin IS. Infection during percutaneous transhepatic biliary drainage.
Surgery 1989;105:239.
6. Hatfield AR, Tobias R, Terblanche J, Girdwood AH, Fataar S, Harries-Jones R, et al.
Preoperative external biliary drainage in obstructive jaundice. A prospective controlled
clinical trial. Lancet 1982;23:896-9.
7. Denning DA, Ellison EC, Carey LC. Preoperative percutaneous transhepatic biliary
decompression lowers operative morbidity in patients with obstructive jaundice. Am J
Surg 1981;141:61-5.
8. Lygidakis NJ, van der Heyde MN, Lubbers MJ. Evaluation of preoperative biliary drainage
in the surgical management of pancreatic head carcinoma. Acta Chir Scand 1987;153:665-8.
9. Whipple AO, Parson WB, Mullins LR. Treatment of carcinoma of ampulla of vater. Ann Surg
1935;102:763-9.
10. Gulati MS, Srinivasan A, Agarwal PP. Percutaneous Management of Malignant Biliary
Obstruction: The Indian Perspective. Tropical Gastroenterology 2003;24:47-58.
11. Ahuja V, Garg PK, Kumar D, Goindi G, Tandon RK. Presence of white bile associated with
lower survival in malignant biliary obstruction. Gastrointest Endosc 2002;55:186-91.
