Ignite Creation Date:
2024-10-26 @ 3:41 PM
Last Modification Date:
2024-10-26 @ 3:41 PM
Study NCT ID:
NCT06614452
Status:
RECRUITING
Last Update Posted:
None
First Post:
2024-09-23
Brief Title:
Endoscopic Ultrasound-guided Fine-needle Biopsy for Tissue Sampling of Biliary Strictures a Multicenter Prospective Study
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Endoscopic Ultrasound-guided Fine-needle Biopsy for Tissue Sampling of Biliary Strictures a Multicenter Prospective Study
Status:
RECRUITING
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
After the disappointing results of first-generation reverse bevel fine-needle biopsy FNB needles newer third generation endoscopic ultrasound EUS needles were developed known as the end-cutting needles These needle types have shown excellent diagnostic accuracy gt90 in pancreatic masses and several other lesions even without rapid on site evaluation ROSE and are not associated with increased adverse event incidence The main design of end-cutting FNB needles are the Franseen type which has three symmetrically distributed needle points and cutting edges and the Fork-tip type which has 2 protruding asymmetrical sharp points and six distal cutting edges however other end-cutting needles are currently available such as the three-prong asymmetric tip needle and the Menghini tip needle
Given the significant increase in diagnostic accuracy and sensitivity observed in other abdominal lesions these needles are expected to improve the diagnostic outcomes of EUS-FNB of pure biliary strictures although clinical data are still lacking
The aim of this study is to ascertain the impact of end-cutting FNB needles in the diagnostic algorithm of biliary strictures in absence of a clear pancreatic or abdominal mass
This is a multicenter international observational prospective study Consecutive patients diagnosed with biliary strictures in absence of a pancreatic or abdominal mass will be assessed for eligibility
Patients with jaundice requiring decompression will undergo endoscopic retrograde cholangiopancreatography ERCP with tissue sampling brushing andor biopsy and biliary drainage preferably in the same session immediately after EUS-FNB
Endoscopic ultrasound will be performed using a curvilinear array echoendoscope FNB with 22G or 25G end-cutting needles will be performed The size of the needles will be based on the personal choice of the endoscopist Likewise the sampling technique whether using the slow-pull the dry suction or the wet suction will be based on the physicians choice Three passes will be performed as per current guidelines Specimens will be collected in 3 vials to allow for analysis according to needle pass one for the first pass one for the second pass and one for the third and any eventual subsequent passes
The ROSE will not be available in this study Primary outcome will be diagnostic sensitivity of EUS-FNB and 45 patients will be prospectically enrolled
Given the significant increase in diagnostic accuracy and sensitivity observed in other abdominal lesions these needles are expected to improve the diagnostic outcomes of EUS-FNB of pure biliary strictures although clinical data are still lacking
The aim of this study is to ascertain the impact of end-cutting FNB needles in the diagnostic algorithm of biliary strictures in absence of a clear pancreatic or abdominal mass
This is a multicenter international observational prospective study Consecutive patients diagnosed with biliary strictures in absence of a pancreatic or abdominal mass will be assessed for eligibility
Patients with jaundice requiring decompression will undergo endoscopic retrograde cholangiopancreatography ERCP with tissue sampling brushing andor biopsy and biliary drainage preferably in the same session immediately after EUS-FNB
Endoscopic ultrasound will be performed using a curvilinear array echoendoscope FNB with 22G or 25G end-cutting needles will be performed The size of the needles will be based on the personal choice of the endoscopist Likewise the sampling technique whether using the slow-pull the dry suction or the wet suction will be based on the physicians choice Three passes will be performed as per current guidelines Specimens will be collected in 3 vials to allow for analysis according to needle pass one for the first pass one for the second pass and one for the third and any eventual subsequent passes
The ROSE will not be available in this study Primary outcome will be diagnostic sensitivity of EUS-FNB and 45 patients will be prospectically enrolled
Detailed Description:
INTRODUCTION Tissue sampling to establish the nature of a stricturing lesion represents a key step in the diagnostic work-up of biliary strictures As already known a significant proportion 70-80 of biliary strictures are malignant higher in patients with a definitive mass lesion than in those without a mass on cross-sectional imaging PMID 23340062 Early diagnosis is thus important for directing patients to the proper therapeutic strategy While transpapillary brush cytology or forceps biopsy after sphincterotomy during endoscopic retrograde cholangiopancreatography ERCP have been the standard sampling modality endoscopic ultrasound EUS-tissue acquisition TA is a useful later addition to the diagnostic armamentarium The pooled sensitivity of brush cytology and intraductal biopsies has been found to be 45 and 481 respectively while the combination of the two only modestly increased the sensitivity to 594 PMID 25440678 On the contrary EUS-TA has been reported to have a pooled diagnostic sensitivity of 83 for distal biliary strictures PMID 26422979 Moreover the choice of the modality adopted would depend not only on the availability of expertise but also on the location of the lesion and presence of jaundice Indeed EUS-TA has shown better sensitivity for distal lesions compared to proximal lesions PMID 26422979
The performance of EUS-TA in peri-hilar strictures showed less favourable results A 2020 prospective evaluation of EUS-fine-needle aspiration FNA in the diagnosis of biliary strictures n97 46 hilar showed an overall sensitivity of 75 CI 64-84 Subgroup sensitivity and negative predictive value NPV reached 95 and 93 for distal lesions without stenting whereas for the group of stented peri-hilar lesions this was much lower at 56 and 33 respectively PMID 33140008
However data on EUS-TA of biliary strictures are based only to EUS-FNA studies whereas data on EUS-fine-needle biopsy FNB are lacking in this setting
In the last three decades the evolution of needles has undergone a remarkable change and is constantly under development by designing innovative tip designs to allow for larger histological specimens with preserved tissue architecture along with use of tissue for genomic profiling and organoids development that are very important in the era of oncological personalized medicine As a result the current era has seen a decisive shift from FNA to FNB needles
EUS-FNA needles have limitations that are well known their diagnostic performance is dependent on a cytopathologist to render a rapid on-site evaluation ROSE no provision of a histological core tissue is possible and insufficient tissue for risk stratification to tailor anti-cancer therapy
After the disappointing results of first-generation reverse bevel FNB needles newer third generation EUS needles were developed known as the end-cutting needles These needle types have shown excellent diagnostic accuracy gt90 in pancreatic masses and several other lesions even without ROSE and are not associated with increased adverse event incidence PMID 37591258 PMID 36990125 PMID 35124072 The main design of end-cutting FNB needles are the Franseen type which has three symmetrically distributed needle points and cutting edges and the Fork-tip type which has 2 protruding asymmetrical sharp points and six distal cutting edges however other end-cutting needles are currently available such as the three-prong asymmetric tip needle and the Menghini tip needle
Given the significant increase in diagnostic accuracy and sensitivity observed in other abdominal lesions these needles are expected to improve the diagnostic outcomes of EUS-FNB of pure biliary strictures although clinical data are still lacking
The aim of this study is to ascertain the impact of end-cutting FNB needles in the diagnostic algorithm of biliary strictures in absence of a clear pancreatic or abdominal mass
STUDY DESIGN Multicenter international observational prospective study This study will be conducted according to the principles and the recommendations of the 2013 Declaration of Helsinki
STUDY PATIENTS Consecutive patients diagnosed with biliary strictures in absence of a pancreatic or abdominal mass will be assessed for eligibility Diagnosis of biliary strictures will be performed according to current guidelines PMID 37307900
Patients with jaundice requiring decompression will undergo ERCP with tissue sampling brushing andor biopsy and biliary drainage preferably in the same session immediately after EUS-FNB
Inclusion criteria
Age 18 years
Suspicious biliary stricture in absence of an abdominal mass at cross-sectional imaging
Distal and peri-hilar biliary strictures
Informed consent provided by the patient or the closest relative
Exclusion criteria
Presence of a pancreatic or abdominal mass structuring the common bile duct
EUS not feasible
Known bleeding disorder that cannot be sufficiently corrected with fresh frozen plasma FFP
Use of anticoagulants that cannot be discontinued
INR gt15 or platelet count lt50000
Pregnancy
PROCEDURAL TECHNIQUE Endoscopic ultrasound will be performed using a curvilinear array echoendoscope FNB with 22G or 25G end-cutting needles will be performed The size of the needles will be based on the personal choice of the endoscopist Likewise the sampling technique whether using the slow-pull the dry suction or the wet suction will be based on the physicians choice Three passes will be performed as per current guidelines Specimens will be collected in 3 vials to allow for analysis according to needle pass one for the first pass one for the second pass and one for the third and any eventual subsequent passes
The rapid-on site cytological evaluation ROSE will not be available in this study
ENDPOINTS Primary Endpoint Primary outcome will be diagnostic sensitivity of EUS-FNB defined as true positivestrue positives false negatives
Secondary Endpoints
Sample adequacy defined as the ability to procure histological samples adequate for diagnostic interpretation A histologic specimen will be defined as an architecturally intact piece of tissue from the target lesion PMID 29074447
Diagnostic accuracy defined as true positive true negative total number of patients The gold standard for the final diagnosis will be the pathological report in the subset of patients undergoing surgery and the clinical follow-up for 6 months in non-surgical patients
Diagnostic specificity defined as true negativestrue negativesfalse positives
Histological quality of the sample quantified using a score for tissue integrity and blood contamination of specimens validated elsewhere PMID 32433914
Yield of each needle pass
Number of needle passes
Adverse events classified according to ASGE lexicon PMID 20189503 Postprocedural AEs will be investigated during follow-up with phone calls at 2 weeks after the procedure
ENROLLMENT AND DROP-OUT Enrollment will be competitive between centers and will extend for a maximum period of 1 year after local Ethic CommitteeIRB approval Patients will be considered dropped-out in case of consent withdrawn or if lost before the end of follow-up
SAMPLE SIZE CALCULATION AND STATISTICAL CONSIDERATIONS On the basis of a previous study PMID 33140008 reporting 75 sensitivity with EUS-FNA of biliary strictures the study is designed to detect an increase in diagnostic yield with end-cutting FNB needles to 948 as reported in a previous meta-analysis PMID 31579703
Therefore 45 patients will be required to have a 90 power to detect the target difference at a 0025 significance level adjusted for multiplicity considering the planned subgroup analysis between peri-hilar and distal biliary strictures and expecting a drop-out rate of 10 A 21 stratification according to the location of the biliary strictures will be considered therefore we expect to enroll 30 patients with distal biliary strictures and 15 patients with peri-hilar biliary strictures
DATA COLLECTED General information
Age years
Sex MF
Charlson comorbidity index
BMI Lesion information
Location
Imaging studies performed
Lesion size mm
Main pancreatic duct MPD dilation
CBD caliber mm Procedural information
Sampling route stomach duodenum
Number of passes
Sampling technique dry suction wet suction slow pull Outcomes
Adequacy at each pass
Sensitivity
Specificity
Accuracy
Quality of sample
Surgery
AEs
Final diagnosis
The performance of EUS-TA in peri-hilar strictures showed less favourable results A 2020 prospective evaluation of EUS-fine-needle aspiration FNA in the diagnosis of biliary strictures n97 46 hilar showed an overall sensitivity of 75 CI 64-84 Subgroup sensitivity and negative predictive value NPV reached 95 and 93 for distal lesions without stenting whereas for the group of stented peri-hilar lesions this was much lower at 56 and 33 respectively PMID 33140008
However data on EUS-TA of biliary strictures are based only to EUS-FNA studies whereas data on EUS-fine-needle biopsy FNB are lacking in this setting
In the last three decades the evolution of needles has undergone a remarkable change and is constantly under development by designing innovative tip designs to allow for larger histological specimens with preserved tissue architecture along with use of tissue for genomic profiling and organoids development that are very important in the era of oncological personalized medicine As a result the current era has seen a decisive shift from FNA to FNB needles
EUS-FNA needles have limitations that are well known their diagnostic performance is dependent on a cytopathologist to render a rapid on-site evaluation ROSE no provision of a histological core tissue is possible and insufficient tissue for risk stratification to tailor anti-cancer therapy
After the disappointing results of first-generation reverse bevel FNB needles newer third generation EUS needles were developed known as the end-cutting needles These needle types have shown excellent diagnostic accuracy gt90 in pancreatic masses and several other lesions even without ROSE and are not associated with increased adverse event incidence PMID 37591258 PMID 36990125 PMID 35124072 The main design of end-cutting FNB needles are the Franseen type which has three symmetrically distributed needle points and cutting edges and the Fork-tip type which has 2 protruding asymmetrical sharp points and six distal cutting edges however other end-cutting needles are currently available such as the three-prong asymmetric tip needle and the Menghini tip needle
Given the significant increase in diagnostic accuracy and sensitivity observed in other abdominal lesions these needles are expected to improve the diagnostic outcomes of EUS-FNB of pure biliary strictures although clinical data are still lacking
The aim of this study is to ascertain the impact of end-cutting FNB needles in the diagnostic algorithm of biliary strictures in absence of a clear pancreatic or abdominal mass
STUDY DESIGN Multicenter international observational prospective study This study will be conducted according to the principles and the recommendations of the 2013 Declaration of Helsinki
STUDY PATIENTS Consecutive patients diagnosed with biliary strictures in absence of a pancreatic or abdominal mass will be assessed for eligibility Diagnosis of biliary strictures will be performed according to current guidelines PMID 37307900
Patients with jaundice requiring decompression will undergo ERCP with tissue sampling brushing andor biopsy and biliary drainage preferably in the same session immediately after EUS-FNB
Inclusion criteria
Age 18 years
Suspicious biliary stricture in absence of an abdominal mass at cross-sectional imaging
Distal and peri-hilar biliary strictures
Informed consent provided by the patient or the closest relative
Exclusion criteria
Presence of a pancreatic or abdominal mass structuring the common bile duct
EUS not feasible
Known bleeding disorder that cannot be sufficiently corrected with fresh frozen plasma FFP
Use of anticoagulants that cannot be discontinued
INR gt15 or platelet count lt50000
Pregnancy
PROCEDURAL TECHNIQUE Endoscopic ultrasound will be performed using a curvilinear array echoendoscope FNB with 22G or 25G end-cutting needles will be performed The size of the needles will be based on the personal choice of the endoscopist Likewise the sampling technique whether using the slow-pull the dry suction or the wet suction will be based on the physicians choice Three passes will be performed as per current guidelines Specimens will be collected in 3 vials to allow for analysis according to needle pass one for the first pass one for the second pass and one for the third and any eventual subsequent passes
The rapid-on site cytological evaluation ROSE will not be available in this study
ENDPOINTS Primary Endpoint Primary outcome will be diagnostic sensitivity of EUS-FNB defined as true positivestrue positives false negatives
Secondary Endpoints
Sample adequacy defined as the ability to procure histological samples adequate for diagnostic interpretation A histologic specimen will be defined as an architecturally intact piece of tissue from the target lesion PMID 29074447
Diagnostic accuracy defined as true positive true negative total number of patients The gold standard for the final diagnosis will be the pathological report in the subset of patients undergoing surgery and the clinical follow-up for 6 months in non-surgical patients
Diagnostic specificity defined as true negativestrue negativesfalse positives
Histological quality of the sample quantified using a score for tissue integrity and blood contamination of specimens validated elsewhere PMID 32433914
Yield of each needle pass
Number of needle passes
Adverse events classified according to ASGE lexicon PMID 20189503 Postprocedural AEs will be investigated during follow-up with phone calls at 2 weeks after the procedure
ENROLLMENT AND DROP-OUT Enrollment will be competitive between centers and will extend for a maximum period of 1 year after local Ethic CommitteeIRB approval Patients will be considered dropped-out in case of consent withdrawn or if lost before the end of follow-up
SAMPLE SIZE CALCULATION AND STATISTICAL CONSIDERATIONS On the basis of a previous study PMID 33140008 reporting 75 sensitivity with EUS-FNA of biliary strictures the study is designed to detect an increase in diagnostic yield with end-cutting FNB needles to 948 as reported in a previous meta-analysis PMID 31579703
Therefore 45 patients will be required to have a 90 power to detect the target difference at a 0025 significance level adjusted for multiplicity considering the planned subgroup analysis between peri-hilar and distal biliary strictures and expecting a drop-out rate of 10 A 21 stratification according to the location of the biliary strictures will be considered therefore we expect to enroll 30 patients with distal biliary strictures and 15 patients with peri-hilar biliary strictures
DATA COLLECTED General information
Age years
Sex MF
Charlson comorbidity index
BMI Lesion information
Location
Imaging studies performed
Lesion size mm
Main pancreatic duct MPD dilation
CBD caliber mm Procedural information
Sampling route stomach duodenum
Number of passes
Sampling technique dry suction wet suction slow pull Outcomes
Adequacy at each pass
Sensitivity
Specificity
Accuracy
Quality of sample
Surgery
AEs
Final diagnosis
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