Ignite Creation Date:
2024-05-05 @ 5:11 PM
Last Modification Date:
2024-10-26 @ 9:29 AM
Study NCT ID:
NCT00409864
Status:
COMPLETED
Last Update Posted:
2010-05-26
First Post:
2006-12-08
Brief Title:
Endoscopic Versus Percutaneous Drainage For Hilar Block in Gall Bladder Cancer
Sponsor:
All India Institute of Medical Sciences New Delhi
Organization:
All India Institute of Medical Sciences New Delhi
Study Overview
Official Title:
Endoscopic Versus Percutaneous Biliary Drainage For Hilar Block Due to Carcinoma Gall Bladder A Randomized Prospective Trial and Quality Of Life Assessment
Status:
COMPLETED
Status Verified Date:
2006-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Cancer of the gallbladder CaGB is one of the most common causes of malignant obstructive jaundice Jaundice is the second most common presentation and occurs in 30-60 of patients with CaGB It is obstructive in nature and frequently associated with pruritus which is very disturbing for the patients The usual mechanism of obstruction is direct infiltration of the bile duct by the tumour Most patients with CaGB with obstructive jaundice are not amenable to a curative surgical resection and hence effective palliation is the goal of treatment Although surgical bypass has been the traditional palliative approach it is associated with substantial morbidity and mortality Non-operative alternatives in the form of percutaneous and endoscopic drainage are available A few trials have shown that endoscopic drainage is better than percutaneous drainage in patients with lower end bile duct obstruction due to pancreatic and peri-ampullary cancer However the scenario is quite different in patients with upper end of bile duct obstruction as occurs due to CaGB Endoscopic drainage is associated with a higher incidence of cholangitis in patients with a block at the upper end of the bile duct and the success rate varies from 40 to 80 while percutaneous drainage may be associated with complications such as biliary leak and bleeding There has been no randomized trial comparing endoscopic and percutaneous drainage in patients with malignant obstruction due to CaGB The objective of the present study is to carry out a randomized prospective trial comparing percutaneous and endoscopic biliary drainage in patients with CaGB with obstructive jaundice and to assess their quality of life
Detailed Description:
Hypothesis Percutaneous biliary stenting is superior to endoscopic stenting in providing successful biliary drainage by 20 in patients with unresectable malignant hilar block due to carcinoma of gall bladder
Background Malignant biliary obstruction at the liver hilum is caused by a heterogeneous group of tumours that include cholangiocarcinoma gallbladder cancer CaGB and metastatic cancer CaGB is the commonest cause of malignant hilar obstruction in India 1 Jaundice is the second most common presentation and occurs in 30-60 of patients with CaGB 2-5 It is obstructive in nature and frequently associated with pruritis which is very disturbing for the patients Most patients with CaGB with surgical obstructive jaundice are not amenable to a curative surgical resection 5 and hence effective palliation is the goal of treatment Although surgical bilioenteric bypass has been the traditional palliative approach 6 it is associated with substantial morbidity and mortality Non-operative alternatives in the form of percutaneous and endoscopic drainage are available 7-8 Unilateral drainage of single liver lobe may be sufficient to palliate the jaundice and pruritis and improve the quality of life 9-15 A few trials have shown that endoscopic drainage is better than percutaneous drainage in patients with lower end bile duct obstruction due to pancreatic and periampullary cancer However the scenario is quite different in patients with hilar malignant obstruction Endoscopic drainage is associated with a higher incidence of cholangitis in patients with a block at the confluence Bismuth types 2 and 3 and the success rate varies from 40 to 80 while percutaneous drainage may be associated with complications such as biliary leak and bleeding There has been no randomized trial comparing endoscopic and percutaneous drainage in patients with malignant hilar obstruction alone
Objective To compare unilateral PTBD and endoscopic stenting in patients with CaGB with hilar block in terms of Successful drainage and Quality of life Patients and Methods Consecutive patients with CaGB and jaundice will be enrolled in the study The diagnosis of CaGB and biliary obstruction will be established on the basis of an ultrasound of the abdomen and a dual phase CT scan Histological andor cytological confirmation of the malignancy will be established wherever possible by doing a FNACtrucut biopsy Hilar block will be classified according to the Bismuth Corlette classification based on the preprocedural investigations 16 Final differentiation between type 2 and 3 blocks will be based on findings noted during intervention
Inclusion criteria CaGB with hilar block not suitable for curative resection with one or more of the following criteria i Jaundice with serum bilirubin 10 mgdl ii Pruritus iii Cholangitis Exclusion criteria Poor performance status Karnofsky index 60 Type 1 and 4 hilar block Uncontrolled ascites Duodenal obstruction Patients who opted for insertion of a metallic stent
Sample size calculation The number of patients to be included was calculated to be 91 patients in each group based on the assumption that percutaneous drainage will be better than endoscopic drainage by 20 The sample size was calculated by the formula for a power of 80 and alpha error of 005
The patients will be randomly divided into two groups using random blocks generated by a computer
Group A - percutaneous biliary drainage PTBD Group B - Endoscopic stenting ES Pre-procedural preparation17 Patients will undergo detailed investigations and an informed consent will be obtained
The procedure will be performed under conscious sedation midazolam and pentozocine with a liberal infiltration of local anesthetic at the site and the capsule of the liver for PTBD
1 PTBD procedure 17 Either a right or left sided approach will be used for PTBD Once entry will be gained to a suitable duct the standard Seldinger technique will be used to place a guidewire in the biliary system The tract will be dilated and after crossing the obstruction with a hydrophilic guidewire a ring biliary catheter will be placed to provide internal-external drainage In a subsequent session a 10 F straight plastic stent polyurethane will be placed into the system across the obstruction to provide internal drainage
2 Endoscopic stenting 18 A therapeutic duodenoscope and a standard sphincterotome will be used for cannulation of the bile duct A hydrophilic guidewire will be used to cross the malignant stricture After the stricture is crossed a guide catheter will be passed over the guidewire and then a 10 F straight plastic stent will be inserted across the stricture over the guidewire
Primary outcome measures
1 Successful drainage A decrease in bilirubin to less than 75 of the pretreatment value within 7 days
2 Early cholangitis Occurring within 48 hours to 7 days of the procedure as evidenced by fever leukocytosis and worsening LFTs
3 Quality of life
Secondary outcome measures
1 Complications
2 Procedure-related and 30-day mortality
3 Stent patency time will be defined by time to stent occlusion
Hematological and biochemical parameters will be assessed at days 2 and 7 1 month after stent placement and every 3 months thereafter Patients will be re-evaluated 7 days 1 month after stent placement and 3 months thereafter
Quality of life will be assessed using the WHO-QOL BREF26 and EORTC QLQ-30 questionnaires pre-procedure at 1 month and at 3 months
World Health Organization-QOL BREF-26 19 This has 26 items which cover physical psychological social and environmental domains The daily activity is graded in accordance with the 5 grade scale of performance status recommended by the WHO WHO-QOL domain scores will be calculated using the guidelines given in the WHO-QOL scoring manual A high score represents a high level of QOL
EORTC QLQ-30 20 The EORTC QLQ-30 consists of 30 generally applicable items It incorporates a functional scale items 1-5 a role functioning scale item 67 a general symptom scale item 8-19 scales on cognitive item 20-25 emotional items 21-24 and social items 26-27 functioning financial strain scale item 28 and global health status scale item 2930 Scoring will be done using the EORTC scoring manual
A high score for a functional scale will represent a highhealthy level of functioning a high score for global health statusQOL will represent high QOL but a high score for symptom scaleitem will represent a higher level of symptomatology problem
All patients will be instructed to contact the department if any symptom suggestive of a complication appeared Additional information regarding current status or death will be obtained by direct contact with the referring physician or the patient by telephoneletter
Statistical analysis Data will be analyzed according to both the intention-to-treat ITT and per protocol PP methods The baseline characteristics will be expressed in mean SD The Pearson chi -square test and Fischer exact test will be used for comparison of categorical data as appropriate The t-test will be used for comparison of continuous variables Cumulative survival will be estimated using Kaplan-Meier life table analysis and the groups will be compared by log rank chi-square test
The QOL score analysis will be done using Paired t test for comparison between baseline and 1 month and baseline and 3 months within the groups MANOVA will be used to assess the trend of the scores
References
1 Malkan G Mohandas KM Epidemiology of digestive cancers in India I General principles and esophageal cancer Indian J Gastroenterol 199716398-102
2 Wanebo HJ Castle WN Fechner RE Is carcinoma of the gall bladder a curable lesion Ann Surg 1982195624-31
3 Kelly TR Chamberlain TR Carcinoma of the gall bladder Am J Surg 1982 143737-41
4 Morrow CF Sutherland DE Florack G Eisenberg MM Grage TB Primary carcinoma gall bladder Significance of subserosal lesions and results of aggressive surgical treatment and adjuvant chemotherapy Surgery 198394709-14
5 Kumaran V Gulati MS Paul SB Pande GK Sahni P Chattopadhyay TK The role of dual phase helical CT in assessing respectability of carinoma of the gall bladder Eur Radiol 2002121993-99
6 Bismuth H Castaing D Traynor O Resection or palliation priority of surgery in the treatment of hilar cancer World J Surg 1988 1239-47
7 Huibregtse K Tytgat GNJ Palliative treatment of jaundice by transpapillary introduction of biliary endoprosthesis Gut 1982 23371-5
8 Cotton PB Endoscopic methods for relief of malignant obstructive jaundice World J Surg 19848854-61
9 Dowsett JF Vaira D Hatfield AR Cairns SR Polydorou AA Frost R et al Endoscopic biliary therapy using the combined percutaneous and endosopic route Gastroenterology 1989961180-6
10 Polydorou AA Cairns SR Dowsett JF Hatfield AR Salmon PR Cotton PB et al Palliation of proximal malignant biliary obstruction by endoscopic endoprosthesis insertion Gut 199132685-9
11 De Palma GD Galloro G Sicilliano S Ivonini P Catanzano C Unilateral versus bilateral endoscopic hepatic duct drainage in patients with malignant hilar biliary obstruction results of a prospective randomized and controlled study Gastrointest Endosc 200153547-53
12 Sherman S Endoscopic drainage of malignant hilar obstruction is one biliary stent enough or should we place two Gastrointest Endosc 200153681-4
13 Chang WH Kortan P Haber GB Outcome in patients with bifurcation tumors who undergo unilateral versus bilateral hepatic duct drainage Gastrointest Endosc 199847354-62
14 Mehta S Ozden ZS Dhanireddy S Pleskow DP Chutanni R Endoscopic single versus double bilateral Wallstents for palliation of malignant Bismuth type IIIIV hilar strictures comparison of clinical outcomes and costs abstract Gastrointest Endosc 199949AB234
15 De Palma Angelo Pezzullo Maria Rega Unilateral placement of metallic stents for malignant hilar obstruction a prospective study Gastrointest Endosc 20035550-5
16 Bismuth H Castaing D Traynor O Resection or palliation priority of surgery in the treatment of hilar cancer World j Surg 19881239-47
17 Gulati MS Srinivasan A Agarwal PP Percutaneous Management of Malignant Biliary Obstruction The Indian Perspective Tropical Gastroenterology 20032447-58
18 Ahuja V Garg PK Kumar D Goindi G Tandon RK Presence of white bile associated with lower survival in malignant biliary obstruction Gastrointest Endosc 200255186-91
19 World Health Organization Handbook for Reporting Results of cancer Treatment World Health Organization Publication No 48 Geneva World Health Organization 1979
20 Aaronson NK Ahmedzai S Bergman B Bullinger M Cull A Duez NJ et al The European Organization for Research and Treatment of Cancer QLQ-C30 a quality-of-life instrument for use in international clinical trials in oncology J Natl Cancer Inst 199385365-76
Background Malignant biliary obstruction at the liver hilum is caused by a heterogeneous group of tumours that include cholangiocarcinoma gallbladder cancer CaGB and metastatic cancer CaGB is the commonest cause of malignant hilar obstruction in India 1 Jaundice is the second most common presentation and occurs in 30-60 of patients with CaGB 2-5 It is obstructive in nature and frequently associated with pruritis which is very disturbing for the patients Most patients with CaGB with surgical obstructive jaundice are not amenable to a curative surgical resection 5 and hence effective palliation is the goal of treatment Although surgical bilioenteric bypass has been the traditional palliative approach 6 it is associated with substantial morbidity and mortality Non-operative alternatives in the form of percutaneous and endoscopic drainage are available 7-8 Unilateral drainage of single liver lobe may be sufficient to palliate the jaundice and pruritis and improve the quality of life 9-15 A few trials have shown that endoscopic drainage is better than percutaneous drainage in patients with lower end bile duct obstruction due to pancreatic and periampullary cancer However the scenario is quite different in patients with hilar malignant obstruction Endoscopic drainage is associated with a higher incidence of cholangitis in patients with a block at the confluence Bismuth types 2 and 3 and the success rate varies from 40 to 80 while percutaneous drainage may be associated with complications such as biliary leak and bleeding There has been no randomized trial comparing endoscopic and percutaneous drainage in patients with malignant hilar obstruction alone
Objective To compare unilateral PTBD and endoscopic stenting in patients with CaGB with hilar block in terms of Successful drainage and Quality of life Patients and Methods Consecutive patients with CaGB and jaundice will be enrolled in the study The diagnosis of CaGB and biliary obstruction will be established on the basis of an ultrasound of the abdomen and a dual phase CT scan Histological andor cytological confirmation of the malignancy will be established wherever possible by doing a FNACtrucut biopsy Hilar block will be classified according to the Bismuth Corlette classification based on the preprocedural investigations 16 Final differentiation between type 2 and 3 blocks will be based on findings noted during intervention
Inclusion criteria CaGB with hilar block not suitable for curative resection with one or more of the following criteria i Jaundice with serum bilirubin 10 mgdl ii Pruritus iii Cholangitis Exclusion criteria Poor performance status Karnofsky index 60 Type 1 and 4 hilar block Uncontrolled ascites Duodenal obstruction Patients who opted for insertion of a metallic stent
Sample size calculation The number of patients to be included was calculated to be 91 patients in each group based on the assumption that percutaneous drainage will be better than endoscopic drainage by 20 The sample size was calculated by the formula for a power of 80 and alpha error of 005
The patients will be randomly divided into two groups using random blocks generated by a computer
Group A - percutaneous biliary drainage PTBD Group B - Endoscopic stenting ES Pre-procedural preparation17 Patients will undergo detailed investigations and an informed consent will be obtained
The procedure will be performed under conscious sedation midazolam and pentozocine with a liberal infiltration of local anesthetic at the site and the capsule of the liver for PTBD
1 PTBD procedure 17 Either a right or left sided approach will be used for PTBD Once entry will be gained to a suitable duct the standard Seldinger technique will be used to place a guidewire in the biliary system The tract will be dilated and after crossing the obstruction with a hydrophilic guidewire a ring biliary catheter will be placed to provide internal-external drainage In a subsequent session a 10 F straight plastic stent polyurethane will be placed into the system across the obstruction to provide internal drainage
2 Endoscopic stenting 18 A therapeutic duodenoscope and a standard sphincterotome will be used for cannulation of the bile duct A hydrophilic guidewire will be used to cross the malignant stricture After the stricture is crossed a guide catheter will be passed over the guidewire and then a 10 F straight plastic stent will be inserted across the stricture over the guidewire
Primary outcome measures
1 Successful drainage A decrease in bilirubin to less than 75 of the pretreatment value within 7 days
2 Early cholangitis Occurring within 48 hours to 7 days of the procedure as evidenced by fever leukocytosis and worsening LFTs
3 Quality of life
Secondary outcome measures
1 Complications
2 Procedure-related and 30-day mortality
3 Stent patency time will be defined by time to stent occlusion
Hematological and biochemical parameters will be assessed at days 2 and 7 1 month after stent placement and every 3 months thereafter Patients will be re-evaluated 7 days 1 month after stent placement and 3 months thereafter
Quality of life will be assessed using the WHO-QOL BREF26 and EORTC QLQ-30 questionnaires pre-procedure at 1 month and at 3 months
World Health Organization-QOL BREF-26 19 This has 26 items which cover physical psychological social and environmental domains The daily activity is graded in accordance with the 5 grade scale of performance status recommended by the WHO WHO-QOL domain scores will be calculated using the guidelines given in the WHO-QOL scoring manual A high score represents a high level of QOL
EORTC QLQ-30 20 The EORTC QLQ-30 consists of 30 generally applicable items It incorporates a functional scale items 1-5 a role functioning scale item 67 a general symptom scale item 8-19 scales on cognitive item 20-25 emotional items 21-24 and social items 26-27 functioning financial strain scale item 28 and global health status scale item 2930 Scoring will be done using the EORTC scoring manual
A high score for a functional scale will represent a highhealthy level of functioning a high score for global health statusQOL will represent high QOL but a high score for symptom scaleitem will represent a higher level of symptomatology problem
All patients will be instructed to contact the department if any symptom suggestive of a complication appeared Additional information regarding current status or death will be obtained by direct contact with the referring physician or the patient by telephoneletter
Statistical analysis Data will be analyzed according to both the intention-to-treat ITT and per protocol PP methods The baseline characteristics will be expressed in mean SD The Pearson chi -square test and Fischer exact test will be used for comparison of categorical data as appropriate The t-test will be used for comparison of continuous variables Cumulative survival will be estimated using Kaplan-Meier life table analysis and the groups will be compared by log rank chi-square test
The QOL score analysis will be done using Paired t test for comparison between baseline and 1 month and baseline and 3 months within the groups MANOVA will be used to assess the trend of the scores
References
1 Malkan G Mohandas KM Epidemiology of digestive cancers in India I General principles and esophageal cancer Indian J Gastroenterol 199716398-102
2 Wanebo HJ Castle WN Fechner RE Is carcinoma of the gall bladder a curable lesion Ann Surg 1982195624-31
3 Kelly TR Chamberlain TR Carcinoma of the gall bladder Am J Surg 1982 143737-41
4 Morrow CF Sutherland DE Florack G Eisenberg MM Grage TB Primary carcinoma gall bladder Significance of subserosal lesions and results of aggressive surgical treatment and adjuvant chemotherapy Surgery 198394709-14
5 Kumaran V Gulati MS Paul SB Pande GK Sahni P Chattopadhyay TK The role of dual phase helical CT in assessing respectability of carinoma of the gall bladder Eur Radiol 2002121993-99
6 Bismuth H Castaing D Traynor O Resection or palliation priority of surgery in the treatment of hilar cancer World J Surg 1988 1239-47
7 Huibregtse K Tytgat GNJ Palliative treatment of jaundice by transpapillary introduction of biliary endoprosthesis Gut 1982 23371-5
8 Cotton PB Endoscopic methods for relief of malignant obstructive jaundice World J Surg 19848854-61
9 Dowsett JF Vaira D Hatfield AR Cairns SR Polydorou AA Frost R et al Endoscopic biliary therapy using the combined percutaneous and endosopic route Gastroenterology 1989961180-6
10 Polydorou AA Cairns SR Dowsett JF Hatfield AR Salmon PR Cotton PB et al Palliation of proximal malignant biliary obstruction by endoscopic endoprosthesis insertion Gut 199132685-9
11 De Palma GD Galloro G Sicilliano S Ivonini P Catanzano C Unilateral versus bilateral endoscopic hepatic duct drainage in patients with malignant hilar biliary obstruction results of a prospective randomized and controlled study Gastrointest Endosc 200153547-53
12 Sherman S Endoscopic drainage of malignant hilar obstruction is one biliary stent enough or should we place two Gastrointest Endosc 200153681-4
13 Chang WH Kortan P Haber GB Outcome in patients with bifurcation tumors who undergo unilateral versus bilateral hepatic duct drainage Gastrointest Endosc 199847354-62
14 Mehta S Ozden ZS Dhanireddy S Pleskow DP Chutanni R Endoscopic single versus double bilateral Wallstents for palliation of malignant Bismuth type IIIIV hilar strictures comparison of clinical outcomes and costs abstract Gastrointest Endosc 199949AB234
15 De Palma Angelo Pezzullo Maria Rega Unilateral placement of metallic stents for malignant hilar obstruction a prospective study Gastrointest Endosc 20035550-5
16 Bismuth H Castaing D Traynor O Resection or palliation priority of surgery in the treatment of hilar cancer World j Surg 19881239-47
17 Gulati MS Srinivasan A Agarwal PP Percutaneous Management of Malignant Biliary Obstruction The Indian Perspective Tropical Gastroenterology 20032447-58
18 Ahuja V Garg PK Kumar D Goindi G Tandon RK Presence of white bile associated with lower survival in malignant biliary obstruction Gastrointest Endosc 200255186-91
19 World Health Organization Handbook for Reporting Results of cancer Treatment World Health Organization Publication No 48 Geneva World Health Organization 1979
20 Aaronson NK Ahmedzai S Bergman B Bullinger M Cull A Duez NJ et al The European Organization for Research and Treatment of Cancer QLQ-C30 a quality-of-life instrument for use in international clinical trials in oncology J Natl Cancer Inst 199385365-76
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