Ignite Creation Date:
2024-05-05 @ 11:53 AM
Last Modification Date:
2024-10-26 @ 9:15 AM
Study NCT ID:
NCT00160836
Status:
UNKNOWN
Last Update Posted:
2007-04-19
First Post:
2005-09-08
Brief Title:
Biliary Tissue Sampling Using a Cytology Brush or the GIUM Catheter
Sponsor:
University Hospital Geneva
Organization:
University Hospital Geneva
Study Overview
Official Title:
Biliary Tissue Sampling Using a Cytology Brush or the GIUM Catheter a Prospective Randomized Controlled Study
Status:
UNKNOWN
Status Verified Date:
2007-04
Last Known Status:
RECRUITING
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:
Introduction In patients with a biliary obstruction tissue is acquired immediately before drainage during endoscopic retrograde cholangio-pancreatography ERCP This is performed by passing a brush inside the bile duct stricture However brush cytology has a modest sensitivity 30-57 for the diagnosis of cancer A device called the GIUM catheter allows for the sampling of higher amounts of tissue during ERCP compared to brush cytology The aim of this study is to compare the diagnostic yield of tissue sampling performed in patients with a suspected malignant biliary stricture using 2 techniques namely a standard brush catheter and the GIUM
Protocol design Eligible patients will have tissue sampling performed using both techniques during ERCP the first technique used being randomly assigned and immediately followed by the other one as well as biliary decompression All specimens obtained will be subjected to cytopathological examination After inclusion of the total number of patients smears will be anonymized and analyzed for diagnosis cell cellularity and quality The final clinical diagnosis in each case will be based on cytologic results plus histological examination of biopsy specimens
Protocol design Eligible patients will have tissue sampling performed using both techniques during ERCP the first technique used being randomly assigned and immediately followed by the other one as well as biliary decompression All specimens obtained will be subjected to cytopathological examination After inclusion of the total number of patients smears will be anonymized and analyzed for diagnosis cell cellularity and quality The final clinical diagnosis in each case will be based on cytologic results plus histological examination of biopsy specimens
Detailed Description:
Introduction
Many patients with a suspected malignant biliary obstruction are considered unsuitable for surgery because of locally advanced or metastatic disease or poor clinical performance status Management of these patients is facilitated by a tissue diagnosis at initial endoscopic retrograde cholangio-pancreatography ERCP This may obviate further invasive tests and the most suitable nonsurgical treatment can be initiated without delay Brush cytology is the most frequently used technique The procedure is relatively easy to perform requires little time and generally is safe Although its specificity is close to 100 brush cytology has a modest sensitivity that ranges from 30 to 57 in most published studies
A device called the GIUM catheter has been developed to increase the amount of tissue available for analysis 1 It consists of a basket with multiple wires that can be passed through the stricture and grasp tissue between the wires It has been shown in an uncontrolled study to allow for the diagnosis of malignancy with a high sensitivity Endoscopy submitted for publication
The aim of this study is to compare the diagnostic yield of tissue sampling performed using a standard brush catheter and the GIUM in patients with a suspected malignant biliary stricture
Selection of patients
Inclusion criteria
Suspicion of malignant biliary stricture without prior histopathologic confirmation
Informed consent for ERCP including sampling and dilation modalities obtained
Exclusion criteria
Coagulopathy not corrected by administration of vitamin K or fresh frozen plasma
Inability to pass a guidewire through the stricture
Hilar stricture
Protocol design and management policy Eligible patients will have tissue sampling performed using both techniques the first technique used being randomly assigned and immediately followed by the other one Randomization will be performed by opening an opaque sealed envelope numbered according to a table of random numbers with blocks of 6 patients each center will receive a pack of 24 numbered envelopes made by an investigation nurse A listing of all patients with a biliary stricture diagnosed at ERCP will be maintained name surname date of birth and date of examination and reason for non inclusion will be stated
Methods of tissue sampling Antibiotics will be administered intravenously 30 minutes before ERCP ERCP with biliary decompression will be performed with standard techniques 2 After bile duct cannulation iopromide Ultravist 300mgImL Berlex Montville NJ will be injected and the level and length of the biliary stricture will be determined A guidewire will be passed through the stricture and intrahepatic opacification will be completed A biliary sphincterotomy will be performed using a standard sphincterotome to facilitate placement of a stent or of a naso-biliary drain Pancreatography will possibly be attempted especially if pancreatic disease is suspected
Tissue sampling will be performed in the order assigned by randomization according to the following technique
Brush the RX-cytology brush M00545000 Boston Scientific Corp Natick Mass will be passed as a unit within its 8 French sheath over the guidewire through the stricture Previous stricture dilation will be left at the discretion of the endoscopist The brushsheath will be withdrawn immediately below the stricture the brush will be moved forth and back within the strictured segment at least 10 times The brush will then be pulled into the catheter still located immediately below the stricture and the unit brushcatheter will be removed A X-ray will be taken with the top of the brush inside the stricture and the X-ray will be kept in a dedicated file as well as a X-ray with the stricture opacified with contrast medium Specimens obtained with the brush will be smeared on glass slides and fixed in 95 ethanol immediately after collection in the ERCP suite Immediately after the brush will be agitated in 10 ml of saline placed in a vial Finally the brush segment will be cut from the supportive wire and placed into a container with CytoLytt solution Cytyc Crawley United Kingdom
GIUM immediately before using the GIUM catheter the biliary stricture will be dilated using a 6-mm in diameter MaxForce balloon catheter Microvasive Endoscopy Boston Sc The GIUM catheter will be passed as a unit within its 85F sheath alongside the guidewire Once the basketsheath is located above the stricture the basket will be opened and passed through the strictured segment 1 time The basket will then be pulled into the catheter and the unit basketcatheter will be removed A X-ray will be taken with the meshes of the GIUM catheter opened inside the stricture and the X-ray will be kept in a dedicated file Specimens obtained with the GIUM will be smeared on glass slides and fixed in 95 ethanol immediately after collection in the ERCP suite Immediately after the GIUM will be agitated in 10 ml of saline placed in a vial Finally all the material remaining between the wires of the GIUM will be rinsed through the sheath into a vial by perfusing 30 ml of CytoLytt solution Cytyc taken from the vial furnished by the manufacturer using a 20-ml sterile syringe into the same vial
Smears as well as the 2 vials of saline and the 2 vials of CytoLytt will be labeled with the patients name and the mark GIUM or brush
Complications possibly detected during ERCP or during the 30 following days will be noted and assessed by using established consensus criteria 3
Preparation of tissue sample Cytolytt vials specimens in Cytolytt will be prepared according to the ThinPrep processor operator manual httpwwwthinprepcom85506Prdgencythtm Specimens obtained with the ThinPrep technique will be processed for 1 slide as described by the manufacturer Cell block inclusion will be performed whenever possible
Smears specimens will be stained by the Papanicolaou technique for standard cytologic examination
Cytopathological examination After inclusion of the total number of patients labels and marks on the smears will be removed and replaced by random numbers Two non-consecutive random numbers from 1 to 1000 will be selected for each patient one for the smear obtained with the GIUM the other for the smear obtained with the brush by JMD Smears will be re-read by two cytopathologists blinded to the name of the patient the technique of tissue sampling previous diagnosis as well as the relationship between the 2 random numbers for each pair of samples collected from the same patient so avoiding interpretation of a sample obtained using one of the 2 techniques with the knowledge of the sample obtained from the same patient using the other technique Indeed their knowledge will be limited to the fact that a biliary stricture was identified at ERCP Final diagnosis will be reached by agreement between the 2 cytopathologists Specimens will be interpreted as normal atypical considered benign highly atypical suspicious for cancer and malignant Cell cellularity and single epithelial cell cellularity will be graded as absent rare moderate or numerous Finally nuclear detail will be graded as poor satisfactory or excellent Other data will be recorded as indicated in Table 1
A list of patients names for whom cell block inclusion has been performed will be kept with indication if it was obtained from material collected with the cytobrush or with the GIUM
Histopathological examination Surgical specimens obtained from patients who undergo duodenopancreatectomy will be subjected to histopathological examination in particular to detect carcinomatous lymphangitis
Statistical analysis The final clinical diagnosis in each case will be based on cytologic results plus specimens obtained at surgery autopsy via percutaneous puncture or endoscopic ultrasonography with fine needle aspiration and disease course including signs of clinical deterioration death or a stable course andor improvement during follow-up Information will be collected by reviewing hospital records and telephone contact with patientsfamilies and referring physicians 1 6 and 12 months after ERCP
For the purpose of calculating sensitivity and specificity all highly atypical suspicious for cancer and malignant diagnoses at cytopathologic examination will be regarded as positive and diagnoses of normal and atypical considered benign will be regarded as negative4 Sensitivity and specificity will be calculated using the Fischer exact test A p value less than 005 will be considered statistically significant
Based on the hypothesis that the sensitivity for the detection of cancer would be 45 4 and 70 on specimens obtained with the brush and the GIUM catheter respectively we calculate that at least 68 patients with a final clinical diagnosis of cancer should be included to reach statistical significance with 5 and 20 alpha and beta error respectively
An interim analysis will be performed after collection of resection specimens in 5 patients to evaluate possible lesions to the biliary tract and surrounding tissues
Many patients with a suspected malignant biliary obstruction are considered unsuitable for surgery because of locally advanced or metastatic disease or poor clinical performance status Management of these patients is facilitated by a tissue diagnosis at initial endoscopic retrograde cholangio-pancreatography ERCP This may obviate further invasive tests and the most suitable nonsurgical treatment can be initiated without delay Brush cytology is the most frequently used technique The procedure is relatively easy to perform requires little time and generally is safe Although its specificity is close to 100 brush cytology has a modest sensitivity that ranges from 30 to 57 in most published studies
A device called the GIUM catheter has been developed to increase the amount of tissue available for analysis 1 It consists of a basket with multiple wires that can be passed through the stricture and grasp tissue between the wires It has been shown in an uncontrolled study to allow for the diagnosis of malignancy with a high sensitivity Endoscopy submitted for publication
The aim of this study is to compare the diagnostic yield of tissue sampling performed using a standard brush catheter and the GIUM in patients with a suspected malignant biliary stricture
Selection of patients
Inclusion criteria
Suspicion of malignant biliary stricture without prior histopathologic confirmation
Informed consent for ERCP including sampling and dilation modalities obtained
Exclusion criteria
Coagulopathy not corrected by administration of vitamin K or fresh frozen plasma
Inability to pass a guidewire through the stricture
Hilar stricture
Protocol design and management policy Eligible patients will have tissue sampling performed using both techniques the first technique used being randomly assigned and immediately followed by the other one Randomization will be performed by opening an opaque sealed envelope numbered according to a table of random numbers with blocks of 6 patients each center will receive a pack of 24 numbered envelopes made by an investigation nurse A listing of all patients with a biliary stricture diagnosed at ERCP will be maintained name surname date of birth and date of examination and reason for non inclusion will be stated
Methods of tissue sampling Antibiotics will be administered intravenously 30 minutes before ERCP ERCP with biliary decompression will be performed with standard techniques 2 After bile duct cannulation iopromide Ultravist 300mgImL Berlex Montville NJ will be injected and the level and length of the biliary stricture will be determined A guidewire will be passed through the stricture and intrahepatic opacification will be completed A biliary sphincterotomy will be performed using a standard sphincterotome to facilitate placement of a stent or of a naso-biliary drain Pancreatography will possibly be attempted especially if pancreatic disease is suspected
Tissue sampling will be performed in the order assigned by randomization according to the following technique
Brush the RX-cytology brush M00545000 Boston Scientific Corp Natick Mass will be passed as a unit within its 8 French sheath over the guidewire through the stricture Previous stricture dilation will be left at the discretion of the endoscopist The brushsheath will be withdrawn immediately below the stricture the brush will be moved forth and back within the strictured segment at least 10 times The brush will then be pulled into the catheter still located immediately below the stricture and the unit brushcatheter will be removed A X-ray will be taken with the top of the brush inside the stricture and the X-ray will be kept in a dedicated file as well as a X-ray with the stricture opacified with contrast medium Specimens obtained with the brush will be smeared on glass slides and fixed in 95 ethanol immediately after collection in the ERCP suite Immediately after the brush will be agitated in 10 ml of saline placed in a vial Finally the brush segment will be cut from the supportive wire and placed into a container with CytoLytt solution Cytyc Crawley United Kingdom
GIUM immediately before using the GIUM catheter the biliary stricture will be dilated using a 6-mm in diameter MaxForce balloon catheter Microvasive Endoscopy Boston Sc The GIUM catheter will be passed as a unit within its 85F sheath alongside the guidewire Once the basketsheath is located above the stricture the basket will be opened and passed through the strictured segment 1 time The basket will then be pulled into the catheter and the unit basketcatheter will be removed A X-ray will be taken with the meshes of the GIUM catheter opened inside the stricture and the X-ray will be kept in a dedicated file Specimens obtained with the GIUM will be smeared on glass slides and fixed in 95 ethanol immediately after collection in the ERCP suite Immediately after the GIUM will be agitated in 10 ml of saline placed in a vial Finally all the material remaining between the wires of the GIUM will be rinsed through the sheath into a vial by perfusing 30 ml of CytoLytt solution Cytyc taken from the vial furnished by the manufacturer using a 20-ml sterile syringe into the same vial
Smears as well as the 2 vials of saline and the 2 vials of CytoLytt will be labeled with the patients name and the mark GIUM or brush
Complications possibly detected during ERCP or during the 30 following days will be noted and assessed by using established consensus criteria 3
Preparation of tissue sample Cytolytt vials specimens in Cytolytt will be prepared according to the ThinPrep processor operator manual httpwwwthinprepcom85506Prdgencythtm Specimens obtained with the ThinPrep technique will be processed for 1 slide as described by the manufacturer Cell block inclusion will be performed whenever possible
Smears specimens will be stained by the Papanicolaou technique for standard cytologic examination
Cytopathological examination After inclusion of the total number of patients labels and marks on the smears will be removed and replaced by random numbers Two non-consecutive random numbers from 1 to 1000 will be selected for each patient one for the smear obtained with the GIUM the other for the smear obtained with the brush by JMD Smears will be re-read by two cytopathologists blinded to the name of the patient the technique of tissue sampling previous diagnosis as well as the relationship between the 2 random numbers for each pair of samples collected from the same patient so avoiding interpretation of a sample obtained using one of the 2 techniques with the knowledge of the sample obtained from the same patient using the other technique Indeed their knowledge will be limited to the fact that a biliary stricture was identified at ERCP Final diagnosis will be reached by agreement between the 2 cytopathologists Specimens will be interpreted as normal atypical considered benign highly atypical suspicious for cancer and malignant Cell cellularity and single epithelial cell cellularity will be graded as absent rare moderate or numerous Finally nuclear detail will be graded as poor satisfactory or excellent Other data will be recorded as indicated in Table 1
A list of patients names for whom cell block inclusion has been performed will be kept with indication if it was obtained from material collected with the cytobrush or with the GIUM
Histopathological examination Surgical specimens obtained from patients who undergo duodenopancreatectomy will be subjected to histopathological examination in particular to detect carcinomatous lymphangitis
Statistical analysis The final clinical diagnosis in each case will be based on cytologic results plus specimens obtained at surgery autopsy via percutaneous puncture or endoscopic ultrasonography with fine needle aspiration and disease course including signs of clinical deterioration death or a stable course andor improvement during follow-up Information will be collected by reviewing hospital records and telephone contact with patientsfamilies and referring physicians 1 6 and 12 months after ERCP
For the purpose of calculating sensitivity and specificity all highly atypical suspicious for cancer and malignant diagnoses at cytopathologic examination will be regarded as positive and diagnoses of normal and atypical considered benign will be regarded as negative4 Sensitivity and specificity will be calculated using the Fischer exact test A p value less than 005 will be considered statistically significant
Based on the hypothesis that the sensitivity for the detection of cancer would be 45 4 and 70 on specimens obtained with the brush and the GIUM catheter respectively we calculate that at least 68 patients with a final clinical diagnosis of cancer should be included to reach statistical significance with 5 and 20 alpha and beta error respectively
An interim analysis will be performed after collection of resection specimens in 5 patients to evaluate possible lesions to the biliary tract and surrounding tissues
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