Evaluation and Management of Refractory Biliary Stricture. J. David Horwhat, MD, FACG Director of Endoscopy Lancaster Gastroenterology, Inc.

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Evaluation and Management of Refractory Biliary Stricture J. David Horwhat, MD, FACG Director of Endoscopy Lancaster Gastroenterology, Inc Outline What defines a refractory biliary stricture Endoscopic and radiographic evaluation Endoscopic treatment Emerging treatments Page 1 of 12

Refractory strictures Benign - treat with drainage Surgical & post-operative strictures Ischemic Anastomotic/post-OLT PSC related Chronic pancreatitis Autoimmune - treat with meds Malignant - operate if able Cholangiocarcinoma Gallbladder cancer Pancreatic cancer Metastatic Refractoriness to diagnosis Page 2 of 12

Reasons for refractoriness What type of stricture is it? Benign Malignant Number Multiple Solitary Length Short or long segment Short Margin Smooth Irregular Transition Smooth Abrupt Shouldering None Present Adapted from Curr Probl Diagn Radiol, January/February 2014 MultiDetecter CT Provides info on vascular and local invasion, nodal and distant mets May be superior to MRCP with extra-hepatic lesions intra- and extra-hepatic dilation on US Sn 75-80%, Sp 60-80% for predicting benign vs malignant Cheaper, widely available Page 3 of 12

MRCP Better for hilar and intra- than MDCT Sn 88%, Sp 95% to diagnose malignancy Sn 98% for level of obstruction Road map for treatment Number - single/multiple Length - helps select size of balloon/stents needed More expensive, risk of motion artifact Ann Intern Med 2003;139:547 57. Endoscopic evaluation ERCP-based Fluoro directed yield Brush cytology 35% Forceps biopsy 48% Cholangioscopy directed yield 78% Sn if intrinsic/intraductal 14% Sn if extrinsic World J Gastrointest Endosc. 2014; 6(4): 137-143 Gastrointest Endosc 2015;81(1):168-76 Page 4 of 12

Reasons for refractoriness Need to improve biopsy yield Increase the number of biopsies taken N=68 sampled by fluoro-directed, N=38 by cholangioscopy Sn for inflam vs dysplas/neoplasia of 45.7% & 58.3%, Sp 100% each, p = 0.992 Rate of True Positives increased with more biopsies taken <6% risk of malignancy if 3 consecutive negative brush cytology results Dig Liv Dis (In Press) DOI: http://dx.doi.org/10.1016/j.dld.2016.03.013 Hepatology. 1990;12:747 52. Improving the yield Add Rapid On Site Evaluation (ROSE) GIE In Press DOI: http://dx.doi.org/10.1016/j.gie.2016.03.1497 Page 5 of 12

Wire-grasp method Gut Liver. 2016 Mar 30. doi: 10.5009/gnl15231. [Epub ahead of print] Endoscopic evaluation EUS based Better for distal/extrahepatic than hilar Mass-like appearance or wall thickness >3 mm EUS FNA vs ERCP based tissue sampling Sn/Acc EUS 94/94% versus ERCP 50/53% Gastrointest Endosc 2014;80:97-104 Page 6 of 12

J. David Horwhat, MD, FACG Gastrointest Endosc 2013;78:868-74 Page 7 of 12

Differentiating PSC from IgG4 sclerosing cholangitis World J Gastroenterol. 2013; 19(43): 7661-7670 Page 8 of 12

Refractoriness to treatment Endoscopic treatment post-olt anastomotic strictures Balloon dilation leave balloon inflated long enough to disrupt stricture may take several minutes dilation + maximal stent therapy is nearly 100% successful in OLT SEMS 80-95% success if >3mo 53-88% when <3mo Gastrointest Endosc. 2013;77(5):679-91 Gastrointest Endosc. 2013;77(1):47-54 Page 9 of 12

Reasons for refractoriness Multiple plastic versus self expanding metal Multiple plastic stents upsize q3m for 1 year 94-100% resolution rate if tx >12 mo 11% recurrence over 13.7yr fu Fully covered self expanding metal stent 81% success removal after 4-6mo Cost and skill considerations Gastrointest Endosc, 2010; 72(3), 551 557 Gastrointest Endosc. 2013;77(5):679-91 Dig Dis Sci. 2015 Nov;60(11):3442-8 Multiple vs csems - 3x10Fr increased to 6x10Fr at 3 mo vs 1x10 mm x 6mo - N= 30 in each group - 2y stricture free rate of 90 and 92%, p = 0.405 JAMA. 2016;315(12):1250-1257 - 1,2 or 3 10Fr (15/35/5) vs 8mm (17) or 10mm (40) csems - Plastic upsized q3, csems q6, assessed at 12mo - Plastic 41/48 (85.4%) vs 50/54 (92.6%) = non-inferior Page 10 of 12

Side by side Hilar strictures Side by side vs stent in stent (or neither) Potential risk of portal vein thrombosis Stent in stent Requires open lattice type stent Clinical efficacy similar How much drainage is needed? 25% drainage of liver resolves jaundice Right 55-60% Left 35% Unilateral vs bilateral no different Gastrointest Endosc 2015; 82(2), 256-67 Emerging therapies Biodegradable stents polydioxanone Drug-eluting stents Steroid injection via SOC Paclitaxel-eluting balloon Rev Col Gastroenterol / 30 (2) 2015 Endoscopy 2015; 47(S 01): E571-E572 Eur Radiol published online 4March2016 Page 11 of 12

Summary Confirm stricture presence/location/size MRCP versus MDCT based on predicted location Obtain tissue diagnosis of benign versus malignant EUS and/or ERCP depending on institutional preference Malignant, operative candidate, offer surgery Autoimmune, treat with steroids Nearly all others get drainage/endoscopic treatment Still waiting for the perfect stent Page 12 of 12