Diagnostic Accuracy of ERCP-guided Versus Cholangioscopy-guided Tissue Acquisition in Patients With Indeterminate Biliary Strictures Suspected to be Intrinsic . (Cholangioscopy)

Diagnostic Accuracy of ERCP-guided Versus Cholangioscopy-guided Tissue Acquisition in Patients With Indeterminate Biliary Strictures Suspected to be Intrinsic .

Diagnostic Accuracy of ERCP-guided Versus Cholangioscopy-guided Tissue Acquisition in Patients With Indeterminate Biliary Strictures Suspected to be Intrinsic - a Randomized Controlled Study

Primary Objective: To assess the diagnostic accuracy of cholangioscopy-based assessment using SpyDS technology compared to cholangiography-based assessment using ERCP-guided biopsy and brushing in patients with indeterminate biliary strictures in the setting of cholangiocarcinoma.

Study Design : Prospective,multi-center, randomized controlled, Post market Study (PMS) Two groups: Control arm - ERCP arm: ERCP impression and ERCP-guided brushing and biopsy Study arm - Cholangioscopy arm: SpyDS impression and SpyDS-guided SpyBite biopsy Randomization 1:1 ratio. Primary Endpoint: Diagnostic accuracy of cholangioscopy or cholangiography assessed at 6 months after initial ERCP procedure Malignancy will be determined by cytology or histology on tissue sampling during the index procedure, or from other tissue acquisition or surgical specimen histopathology up to 6 months after the index procedure. Overall diagnostic accuracy. The assessed strictures will be considered benign if there was no confirmation of malignancy by 6 months after the index procedure. Overall diagnostic accuracy will be assessed for ERCP impression of malignancy ERCP-guided brushing and biopsies separately and combined* SpyDS impression of malignancy SpyBite biopsies In case of discordant results, the following will be followed for the combined pathology/cytology measure: If at least one is malignancy, then combine metric is malignant If both are benign or one is benign and one is non-diagnostic, then combined metric is benign If both are non-diagnostic, then combined metric is non-diagnostic Secondary Endpoints: Occurrence and severity of procedure related serious adverse events from index procedure through 30 days after procedure. Hospitalization and ICU admissions Technical success of procedure defined as ability to collect tissue deemed adequate for cytology or histology. Indeterminate or equivocal or atypical or non-conclusive cytology or histology will be considered failures to this endpoint. Correlation between impression of malignancy and cytopathology in the ERCP arm compared to the Cholangioscopy arm. Additional diagnostic accuracy metrics: Sensitivity, specificity, positive predictive value, negative predictive value. The assessed strictures will be considered benign if there was no confirmation of malignancy by 6 months after the index procedure. Impact of ERCP or cholangioscopy on patient management. Need for additional diagnostic procedures beyond the index procedure. Procedural measures: Type and number of devices used, Duration of procedure from duodenoscope in to duodenoscope out

Control arm- If a patient is randomized to the Control arm, then the procedure will consist of the following: ERC with recording of ERC-based impression of malignancy .ERC-guided biopsies will be collected, consisting of 6 macroscopically visible biopsies. The biopsy forceps / brush will be selected per investigator preference. ERC-guided brushing will be performed, consisting of 10 through-and-fro passes through the target lesion. After this a biliary stent will be placed under ERC-guidance if needed. A biliary sphincterotomy will be performed as needed

If patient is randomized to the Study arm, then the procedure will consist of the following in order: Cannulation and sphincterotomy per standard of practice. POCS with recording of POCS-based impression of malignancy (yes/no/indeterminate). POCS will be performed using the Spy DS system. POCS-guided biopsies will be collected, consisting of 6 macroscopically visible biopsies. The POCS-guided biopsy forceps will be the SpyBite forceps.

If patient is randomized to the Study arm, then the procedure will consist of the following in order: Cannulation and sphincterotomy per standard of practice. POCS with recording of POCS-based impression of malignancy (yes/no/indeterminate). POCS will be performed using the Spy DS system. POCS-guided biopsies will be collected, consisting of 6 macroscopically visible biopsies. The POCS-guided biopsy forceps will be the SpyBite forceps.

• If patients are randomized to the Control arm, then they will undergo an ERCP. ERCP-based impression of malignancy (yes/no/indeterminate) will be recorded. ERCP-guided brushing and ERCP-guided biopsy will be performed.

Malignancy will be determined by cytology or histology on tissue sampling during the index procedure, or from other tissue acquisition or surgical specimen histopathology up to 6 months after the index procedure.The assessed strictures will be considered benign if there was no confirmation of malignancy by 6 months after the index procedure. • Overall diagnostic accuracy will be assessed for ERCP impression of malignancy, ERCP-guided brushing and biopsies separately and combined, SpyDS impression of malignancy and SpyBite biopsies

Occurrence and severity of procedure related serious adverse events from index procedure through 30 days after procedure.

Technical success of procedure defined as ability to collect tissue deemed adequate for cytology or histology. Indeterminate or equivocal or atypical or non-conclusive cytology or histology will be considered failures to this endpoint

Additional diagnostic accuracy metrics: Sensitivity, specificity, positive predictive value, negative predictive value.

Additional diagnostic accuracy metrics: Sensitivity, specificity, positive predictive value, negative predictive value. The assessed strictures will be considered benign if there was no confirmation of malignancy by 6 months after the index procedure

Number of patients in whom management plan is altered based on ERCP or cholangioscopy will be determined

Number of patients needed additional diagnostic procedures beyond the index procedure for final diagnosis

Correlation between impression of malignancy and cytopathology in the ERCP arm compared to the cholangioscopy arm

Number of participants will be compared for outcome of visual impression ( benign/ malignant disease) on ERCP or cholangioscopy with final out come of cytopathology in both arms.

Inclusion Criteria: Age 18 or older. Willing and able to comply with the study procedures and provide written informed consent to participate in the study Biliary obstructive symptoms Indeterminate biliary stricture suspected to be intrinsic based on prior imaging Exclusion Criteria: Contraindications for endoscopic techniques Prior ERCP for assessment of indeterminate biliary stricture Pancreatic head mass identified on prior non-invasive imaging and thought to be the cause of the biliary obstructive symptoms

Gerges C, Beyna T, Tang RSY, Bahin F, Lau JYW, van Geenen E, Neuhaus H, Nageshwar Reddy D, Ramchandani M. Digital single-operator peroral cholangioscopy-guided biopsy sampling versus ERCP-guided brushing for indeterminate biliary strictures: a prospective, randomized, multicenter trial (with video). Gastrointest Endosc. 2020 May;91(5):1105-1113. doi: 10.1016/j.gie.2019.11.025. Epub 2019 Nov 25.