ERCP for the Diagnosis and Management of PSC Vinay Chandrasekhara, M.D. June 21, 2019

Endoscopic Retrograde Cholangio-Pancreatography http://patients.gi.org/topics/ercp-a-patients-guide/

https://www.olympus-europa.com/medical/en/medical_systems/ applications/gastroenterology_1/endoscopic_retrograde_chloangiopancreatography__ ercp_/endoscopic_retrograde_cholangiopancreatography__ercp_.html

Role of ERCP in PSC Diagnosis Tissue sampling Treatment Treatment of strictures Removal of stones Treatment of cholangitis (infection of the bile duct)

ERCP for diagnosing PSC

MRCP ERCP

ERCP for tissue sampling Brushing Cytology Fluorescent in situ hybridization (FISH) Forceps biopsy Cholangioscopy-guided biopsies

Brushing Biopsy

Cholangioscopy

SINGLE OPERATOR CHOLANGIOSCOPY-DIRECTED BIOPSIES IMPROVES DIAGNOSTIC YIELD FOR CHOLANGIOCARCINOMA AND IS SAFE IN PATIENTS WITH PRIMARY SCLEROSING CHOLANGITIS Karan Kaura, MBBS, Tarek Sawas, MD, Fateh Bazerbachi, MD, Mark D. Topazian, MD, John A. Martin, MD, Barham K. Abu Dayyeh, MD, Michael J. Levy, MD, Andrew C. Storm, MD, Gregory J. Gores, MD, Bret T. Petersen, MD, Vinay Chandrasekhara, MD Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, United States Background Baseline Characteristics Procedural Characteristics Parallel comparison in patients who received all modalities of tissue acquisition, n=49 Single operator cholangioscopy (SOC) has been suggested to improve sensitivity and diagnostic accuracy in for the detection of malignancy in patients with primary sclerosing cholangitis (PSC), yet data are limited. Reported rates of high diagnostic accuracy for SOC have been due to the visual impression with cholangioscopy rather than based on tissue acquired during the procedure. PATIENT CHARACTERISTICS PSC (n=36) Non PSC (n=56) Mean age ± SD, years 61 ± 11 54 ± 14 Male sex  22 (61%)  30 (54%) Biliary Stricture Anatomical location Extra-hepatic duct Peri-hilar/Intrahepatic Multiple segments   13 (36.1%) 14 (38.8%) 9 (25%) 20 (35.7%) 14 (25%) 22 (39%) Mass seen on CT/MRI 7 (19%) 17 (30%) Cholangiocarcinoma 17 (47%) 24 (43%) Median follow up after SOC, months (IQR) 32 (9.5 – 82.3) 11.56 (6.7 – 26.9) PROCEDURE CHARACTERISTICS (n=36) PSC Non PSC (n=56) P value Performance of stricture dilation 13 (36%) 14 (25%)   Peri-procedural Antibiotics 23 (64%) 37 (66%) Post- procedure antibiotics 26 (72%) 36 (64%) Indomethacin suppository 1 (3%) 8 (14%)  0.06 Procedural related adverse events Post-ERCP Pancreatitis Post-ERCP pain Upper GI Bleeding Wire Perforation Infection within 30 days 5 (14%) 0 (0%) 3 (8%) 13 (23.2%) 2 (4%) 7 (12%) 1 (2%) 0.27    Sensitivity (95% CI) Specificity PPV NPV Cytology 46.2% (26.6% - 66.6%) 82.6% (61.2% - 95.0%) 75.0% (47.6% -92.7%) 57.6% (39.2% - 74.5%) Cytology + FISH 57.7% (36.9% - 76.6%) 78.9% (54.4% - 93.9%) 63.3% (43.9% - 80.1%) Cytology + FISH + SOC-guided biopsy 69.2% (48.2% - 85.7%) 81.8% (59.7% - 94.8%) 70.4% (49.8% - 86.2%) Cytology + FISH + Transpapillary biopsy Cytology + FISH+ SOC-guided biopsy + transpapillary biopsy (61.2% - 95.0%) Aims Primary aim was to compare the performance characteristics of SOC- guided biopsies and/or endoscopic transpapillary forceps biopsies in addition to conventional brush cytology and FISH for diagnosing cholangiocarcinoma (CCA) in patients with and without PSC. Secondary aim was to assess the safety profile of SOC in patients with PSC. Methods The study analyzed consecutive patients who underwent ERCP with SOC from January 2007 to November 2018 at a single institution. Procedural outcomes, pathology reports, and postprocedural adverse outcomes were recorded. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated in reference to the final clinical and pathologic diagnosis of CCA using the exact binomial test. Sensitivity was compared using exact McNemar test exclusively among patients with CCA. All statistical analyses were performed using STATA 14.0 (StataCorp, College Station, TX). Performance characteristics of tissue sampling techniques for the detection of cholangiocarcinoma Overall Patients, n=92 Sensitivity (95% CI) Specificity (95% CI) PPV (95% CI) NPV (95% CI) Cytology, n=85 44.7% (28.6% - 61.7%) 89.4% (76.9% - 96.5%) 77.3% (54.6% - 92.2%) 66.7% (53.7% - 78.0%) Cytology + FISH, n=85 56.8% (39.5% - 72.9%) 80.8% (60.6% - 93.4%) 72.4% (59.1% - 83.3%) Cytology + FISH + SOC-guided biopsy, n=58 71.4% (51.3% - 86.8%) 86.7% (69.3% - 96.2%) 83.3% (62.6% - 95.3%) 76.5% (58.8% - 89.3%) Cytology + FISH + Transpapillary biopsy, n=64 64.5% (45.4% - 80.8%) 84.8% (68.1% - 94.9%) 80.0% (59.3% - 93.2%) 71.8% (55.1% - 85.0%) Cytology + FISH + SOC-guided biopsy + Transpapillary biopsy, n=49 69.2% (48.2% - 85.7%) 82.6% (61.2% - 95.0%) 81.8% (59.7% - 94.8%) 70.4% (49.8% - 86.2%) Patients with Primary Sclerosing Cholangitis, n=36 Cytology, n=35 50.0% (24.7% - 75.3%) 89.5% (66.9% - 98.7%) (44.4% - 97.5%) 68.0% (46.5% - 85.1%) Cytology + FISH, n=35 62.5% (35.4% - 84.8%) (51.6% - 97.9%) 73.9% (51.6% - 89.8%) Cytology + FISH + SOC-guided biopsy, n=23 63.6% (30.8% - 89.1%) 77.8% (40.0% -97.2%) (41.9% - 91.6%) Cytology + FISH + Transpapillary biopsy, n=24 58.3% (27.7% - 84.8%) (51.6% -97.9%) (40.0% - 97.2%) (30.8% - 89.1% ) Cytology + FISH + SOC-guided biopsy + Transpapillary biopsy, n=19 60.0% (26.2% - 87.8%) 75.0% (34.9% - 96.8%) Conclusions SOC-guided biopsy and transpapillary biopsy improved sensitivity for the detection of malignancy in the overall patient cohort. However, in patients with PSC, SOC-guided biopsy and transpapillary biopsy did not improve diagnostic sensitivity for the detection of cholangiocarcinoma. SOC is safe in patients with PSC. There were no increased rates of post-ERCP pancreatitis, pain, or infection noted in patients with PSC compared to those without PSC. Further prospective studies are needed to determine the role of targeted SOC-guided biopsies and/or transpapillary biopsies for sampling of strictures in patients with PSC. Results The study cohort included 92 patients with indeterminate biliary strictures. 36 with PSC, 56 without PSC. In the overall study cohort, SOC-guided biopsies improved sensitivity in combination with brush cytology and FISH for the detection of CCA compared to brush cytology + FISH (71.4% vs 56.8%; p=0.03). In the overall study cohort, transpapillary biopsies improved sensitivity in combination with brush cytology and FISH for the detection of CCA compared to brush cytology + FISH (64.5% vs 56.8%; p=0.01). In patients with PSC, SOC-guided biopsies in combination with brush cytology and FISH did not improve sensitivity for the detection of CCA compared to brush cytology + FISH (63.6% vs 62.5%, p=NS), In patients with PSC, transpapillary biopsies in combination with brush cytology and FISH did not improve sensitivity for the detection of CCA compared to brush cytology + FISH (58.3% vs 62.5%; p=NS) SOC is safe in patients with PSC with a nonsignificant trend towards lower rates of pancreatitis, pain and infection.

ERCP with dilation for treatment of strictures Balloon Dilation

ERCP with stenting for treatment of strictures

ERCP for removal of stones http://patients.gi.org/topics/ercp-a-patients-guide/

ERCP for treatment of cholangitis

Risks of ERCP in PSC Pancreatitis Bleeding Infection Perforation 5% - 10% Bleeding 1% - 3% Infection Perforation < 1%