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Endoscopic Diagnosis and Therapy in Primary Sclerosing Cholangitis

  • Pancreas (C Forsmark, Section Editor)
  • Published:
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Abstract

Purpose of review

Primary sclerosing cholangitis (PSC) is a progressive idiopathic fibrosing liver disease which leads to multiple biliary complications often best managed with endoscopic retrograde cholangiopancreatography (ERCP).

Recent findings

PSC biliary complications include dominant biliary strictures, bile duct stones, cholangitis, and cholangiocarcinoma (CCA). Balloon dilation is the preferred treatment for management of dominant strictures as biliary stenting has been associated with higher rates of adverse events (AEs). Biliary stenting is reserved for patients with benign refractory strictures or CCA. Multiple tools are available for biliary tissue acquisition including endoscopic ultrasound, biliary brushing for cytology, and fluorescent in situ hybridization (FISH), cholangioscopy, and transpapillary biopsy. The combination of FISH and cytology improve the sensitivity of biliary brush sampling for malignancy. Cholangioscopy improves tissue acquisition in equivocal situations. Obtaining at least 3 biopsy samples yield better results with transpapillary biopsy. Post-ERCP AEs are similar to the general population. However, cholangitis can result from inadvertent contrast introduction into undrainable segments and thus PSC patients should receive peri-procedural antibiotics.

Summary

ERCP-directed interventions are effective for therapy of PSC biliary complications. Tissue sampling for CCA is challenging but multiple tools are available and combinations of these techniques are often required to obtain a tissue diagnosis.

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References

  1. Chapman R, Fevery J, Kalloo A, Nagorney DM, Boberg KM, Shneider B, et al. Diagnosis and management of primary sclerosing cholangitis. Hepatology. 2010;51(2):660–78.

    Article  CAS  PubMed  Google Scholar 

  2. Tischendorf JJ, Hecker H, Kruger M, Manns MP, Meier PN. Characterization, outcome, and prognosis in 273 patients with primary sclerosing cholangitis: a single center study. Am J Gastroenterol. 2007;102(1):107–14.

    Article  PubMed  Google Scholar 

  3. Lindor KD, Kowdley KV, Harrison ME, American College of G. ACG clinical guideline: primary Sclerosing cholangitis. Am J Gastroenterol. 2015;110(5):646–59.

  4. Broome U, Olsson R, Loof L, Bodemar G, Hultcrantz R, Danielsson A, et al. Natural history and prognostic factors in 305 Swedish patients with primary sclerosing cholangitis. Gut. 1996;38(4):610–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Takakura WR, Tabibian JH, Bowlus CL. The evolution of natural history of primary sclerosing cholangitis. Curr Opin Gastroenterol. 2017;33(2):71–7.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Dave M, Elmunzer BJ, Dwamena BA, Higgins PD. Primary sclerosing cholangitis: meta-analysis of diagnostic performance of MR cholangiopancreatography. Radiology. 2010;256(2):387–96.

    Article  PubMed  Google Scholar 

  7. Stiehl A, Rudolph G, Kloters-Plachky P, Sauer P, Walker S. Development of dominant bile duct stenoses in patients with primary sclerosing cholangitis treated with ursodeoxycholic acid: outcome after endoscopic treatment. J Hepatol. 2002;36(2):151–6.

    Article  PubMed  Google Scholar 

  8. Bjornsson E, Lindqvist-Ottosson J, Asztely M, Olsson R. Dominant strictures in patients with primary sclerosing cholangitis. Am J Gastroenterol. 2004;99(3):502–8.

    Article  PubMed  Google Scholar 

  9. • Aabakken L, Karlsen TH, Albert J, Arvanitakis M, Chazouilleres O, Dumonceau JM, et al. Role of endoscopy in primary sclerosing cholangitis: European Society of Gastrointestinal Endoscopy (ESGE) and European Association for the Study of the Liver (EASL) clinical guideline. Endoscopy. 2017;49(6):588–608 This is the most recent European guidelines for the role of endoscopy in manging primary sclerosing cholangitis.

    Article  PubMed  Google Scholar 

  10. Okolicsanyi L, Fabris L, Viaggi S, Carulli N, Podda M, Ricci G. Primary sclerosing cholangitis: clinical presentation, natural history and prognostic variables: an Italian multicentre study. The Italian PSC study group. Eur J Gastroenterol Hepatol. 1996;8(7):685–91.

    CAS  PubMed  Google Scholar 

  11. Wiesner RH, Grambsch PM, Dickson ER, Ludwig J, MacCarty RL, Hunter EB, et al. Primary sclerosing cholangitis: natural history, prognostic factors and survival analysis. Hepatology. 1989;10(4):430–6.

    Article  CAS  PubMed  Google Scholar 

  12. Chapman MH, Webster GJ, Bannoo S, Johnson GJ, Wittmann J, Pereira SP. Cholangiocarcinoma and dominant strictures in patients with primary sclerosing cholangitis: a 25-year single-centre experience. Eur J Gastroenterol Hepatol. 2012;24(9):1051–8.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Kaya M, Petersen BT, Angulo P, Baron TH, Andrews JC, Gostout CJ, et al. Balloon dilation compared to stenting of dominant strictures in primary sclerosing cholangitis. Am J Gastroenterol. 2001;96(4):1059–66.

    Article  CAS  PubMed  Google Scholar 

  14. Baluyut AR, Sherman S, Lehman GA, Hoen H, Chalasani N. Impact of endoscopic therapy on the survival of patients with primary sclerosing cholangitis. Gastrointest Endosc. 2001;53(3):308–12.

    Article  CAS  PubMed  Google Scholar 

  15. Gluck M, Cantone NR, Brandabur JJ, Patterson DJ, Bredfeldt JE, Kozarek RA. A twenty-year experience with endoscopic therapy for symptomatic primary sclerosing cholangitis. J Clin Gastroenterol. 2008;42(9):1032–9.

    Article  PubMed  Google Scholar 

  16. •• Rupp C, Hippchen T, Bruckner T, Kloters-Plachky P, Schaible A, Koschny R, et al. Effect of scheduled endoscopic dilatation of dominant strictures on outcome in patients with primary sclerosing cholangitis. Gut. 2019;68(12)2170–8. This retrospective controlled study demonstrated transplant free survival benifit for scheduled balloon dilation compared to the conventional as needed biliary dilation in patients with PSC.

  17. •• Ponsioen CY, Arnelo U, Bergquist A, Rauws EA, Paulsen V, Cantu P, et al. No superiority of stents vs balloon dilatation for dominant strictures in patients with primary sclerosing cholangitis. Gastroenterology. 2018;155(3):752–9 e5 This open label clinical trial supports the use of balloon dilation alone compared to biliary stenting in PSC patients due to concern for higher adverse events with stenting without added benefit.

    Article  PubMed  Google Scholar 

  18. Ponsioen CY, Lam K, van Milligen de Wit AW, Huibregtse K, Tytgat GN. Four years experience with short-term stenting in primary sclerosing cholangitis. Am J Gastroenterol. 1999;94(9):2403–7.

    Article  CAS  PubMed  Google Scholar 

  19. Kaplan GG, Laupland KB, Butzner D, Urbanski SJ, Lee SS. The burden of large and small duct primary sclerosing cholangitis in adults and children: a population-based analysis. Am J Gastroenterol. 2007;102(5):1042–9.

    Article  PubMed  Google Scholar 

  20. Pohl J, Ring A, Stremmel W, Stiehl A. The role of dominant stenoses in bacterial infections of bile ducts in primary sclerosing cholangitis. Eur J Gastroenterol Hepatol. 2006;18(1):69–74.

    Article  PubMed  Google Scholar 

  21. Rosen CB, Nagorney DM, Wiesner RH, Coffey RJ Jr, LaRusso NF. Cholangiocarcinoma complicating primary sclerosing cholangitis. Ann Surg. 1991;213(1):21–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Rea DJ, Heimbach JK, Rosen CB, Haddock MG, Alberts SR, Kremers WK, et al. Liver transplantation with neoadjuvant chemoradiation is more effective than resection for hilar cholangiocarcinoma. Ann Surg. 2005;242(3):451–8; discussion 458–61.

  23. Sinakos E, Saenger AK, Keach J, Kim WR, Lindor KD. Many patients with primary sclerosing cholangitis and increased serum levels of carbohydrate antigen 19-9 do not have cholangiocarcinoma. Clin Gastroenterol Hepatol. 2011;9(5):434–9 e1.

    Article  CAS  PubMed  Google Scholar 

  24. Weilert F, Bhat YM, Binmoeller KF, Kane S, Jaffee IM, Shaw RE, et al. EUS-FNA is superior to ERCP-based tissue sampling in suspected malignant biliary obstruction: results of a prospective, single-blind, comparative study. Gastrointest Endosc. 2014;80(1):97–104.

    Article  PubMed  Google Scholar 

  25. Rosen CB, Heimbach JK, Gores GJ. Liver transplantation for cholangiocarcinoma. Transpl Int. 2010;23(7):692–7.

    Article  PubMed  Google Scholar 

  26. Razumilava N, Gleeson FC, Gores GJ. Awareness of tract seeding with endoscopic ultrasound tissue acquisition in perihilar cholangiocarcinoma. Am J Gastroenterol. 2015;110(1):200.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Charatcharoenwitthaya P, Enders FB, Halling KC, Lindor KD. Utility of serum tumor markers, imaging, and biliary cytology for detecting cholangiocarcinoma in primary sclerosing cholangitis. Hepatology. 2008;48(4):1106–17.

    Article  CAS  PubMed  Google Scholar 

  28. Trikudanathan G, Navaneethan U, Njei B, Vargo JJ, Parsi MA. Diagnostic yield of bile duct brushings for cholangiocarcinoma in primary sclerosing cholangitis: a systematic review and meta-analysis. Gastrointest Endosc. 2014;79(5):783–9.

    Article  PubMed  Google Scholar 

  29. Amog-Jones GF, Chandra S, Jensen C, Johlin FC. Including the sheath rinse to improve cellular yield in biliary brushing cytology. Clin Endosc. 2017;50(6):614–6.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Farrell RJ, Jain AK, Brandwein SL, Wang H, Chuttani R, Pleskow DK. The combination of stricture dilation, endoscopic needle aspiration, and biliary brushings significantly improves diagnostic yield from malignant bile duct strictures. Gastrointest Endosc. 2001;54(5):587–94.

    Article  CAS  PubMed  Google Scholar 

  31. Moreno Luna LE, Kipp B, Halling KC, Sebo TJ, Kremers WK, Roberts LR, et al. Advanced cytologic techniques for the detection of malignant pancreatobiliary strictures. Gastroenterology. 2006;131(4):1064–72.

    Article  PubMed  Google Scholar 

  32. Bergquist A, Tribukait B, Glaumann H, Broome U. Can DNA cytometry be used for evaluation of malignancy and premalignancy in bile duct strictures in primary sclerosing cholangitis? J Hepatol. 2000;33(6):873–7.

    Article  CAS  PubMed  Google Scholar 

  33. Kipp BR, Stadheim LM, Halling SA, Pochron NL, Harmsen S, Nagorney DM, et al. A comparison of routine cytology and fluorescence in situ hybridization for the detection of malignant bile duct strictures. Am J Gastroenterol. 2004;99(9):1675–81.

    Article  PubMed  Google Scholar 

  34. Barr Fritcher EG, Voss JS, Brankley SM, Campion MB, Jenkins SM, Keeney ME, et al. An optimized set of fluorescence in situ hybridization probes for detection of pancreatobiliary tract cancer in cytology brush samples. Gastroenterology. 2015;149(7):1813–24.

  35. Navaneethan U, Njei B, Venkatesh PG, Vargo JJ, Parsi MA. Fluorescence in situ hybridization for diagnosis of cholangiocarcinoma in primary sclerosing cholangitis: a systematic review and meta-analysis. Gastrointest Endosc. 2014;79(6):943–50 e3.

    Article  PubMed  Google Scholar 

  36. Levy MJ, Baron TH, Clayton AC, Enders FB, Gostout CJ, Halling KC, et al. Prospective evaluation of advanced molecular markers and imaging techniques in patients with indeterminate bile duct strictures. Am J Gastroenterol. 2008;103(5):1263–73.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Barr Fritcher EG, Kipp BR, Voss JS, Clayton AC, Lindor KD, Halling KC, et al. Primary sclerosing cholangitis patients with serial polysomy fluorescence in situ hybridization results are at increased risk of cholangiocarcinoma. Am J Gastroenterol. 2011;106(11):2023–8.

    Article  PubMed  Google Scholar 

  38. Sugiyama M, Atomi Y, Wada N, Kuroda A, Muto T. Endoscopic transpapillary bile duct biopsy without sphincterotomy for diagnosing biliary strictures: a prospective comparative study with bile and brush cytology. Am J Gastroenterol. 1996;91(3):465–7.

    CAS  PubMed  Google Scholar 

  39. Kimura H, Matsubayashi H, Sasaki K, Ito H, Hirosawa K, Uesaka K, et al. Factors affecting the yield of endoscopic transpapillary bile duct biopsy for the diagnosis of pancreatic head cancer. Pancreatology. 2013;13(5):524–9.

    Article  PubMed  Google Scholar 

  40. Ponchon T, Gagnon P, Berger F, Labadie M, Liaras A, Chavaillon A, et al. Value of endobiliary brush cytology and biopsies for the diagnosis of malignant bile duct stenosis: results of a prospective study. Gastrointest Endosc. 1995;42(6):565–72.

    Article  CAS  PubMed  Google Scholar 

  41. Ren YC, Huang CL, Chen SM, Zhao QY, Wan XJ, Li BW. Dilation catheter-guided mini-forceps biopsy improves the diagnostic accuracy of malignant biliary strictures. Endoscopy. 2018;50(8):809–12.

    Article  PubMed  Google Scholar 

  42. Wright ER, Bakis G, Srinivasan R, Raju R, Vittal H, Sanders MK, et al. Intraprocedural tissue diagnosis during ERCP employing a new cytology preparation of forceps biopsy (smash protocol). Am J Gastroenterol. 2011;106(2):294–9.

    Article  PubMed  Google Scholar 

  43. Lo DY, Howell DA, Wright E, Lewis J, Bakis G, Dressel DM, et al. Su1429 frozen section of ERCP forceps biopsy specimens permits efficient intraprocedural diagnosis. Gastrointest Endosc. 2011;73(4):AB263.

    Article  Google Scholar 

  44. Sakuma Y, Kodama Y, Sogabe Y, Nakai Y, Yamashita Y, Mikami S, et al. Diagnostic performance of a new endoscopic scraper for malignant biliary strictures: a multicenter prospective study. Gastrointest Endosc. 2017;85(2):371–9.

    Article  PubMed  Google Scholar 

  45. Tischendorf JJ, Kruger M, Trautwein C, Duckstein N, Schneider A, Manns MP, et al. Cholangioscopic characterization of dominant bile duct stenoses in patients with primary sclerosing cholangitis. Endoscopy. 2006;38(7):665–9.

    Article  CAS  PubMed  Google Scholar 

  46. Kaura K, Sawas T, Bazerbachi F, Martin JA, Abu Dayyeh BK, Storm AC, et al. Single operator cholangioscopy-directed biopsies improves diagnostic yield for cholangiocarcinoma and is safe in patients with primary sclerosing cholangitis. Gastrointest Endosc. 2019;89(6):AB244.

    Article  Google Scholar 

  47. Heif M, Yen RD, Shah RJ. ERCP with probe-based confocal laser endomicroscopy for the evaluation of dominant biliary stenoses in primary sclerosing cholangitis patients. Dig Dis Sci. 2013;58(7):2068–74.

    Article  CAS  PubMed  Google Scholar 

  48. Kalaitzakis E, Sturgess R, Kaltsidis H, Oppong K, Lekharaju V, Bergenzaun P, et al. Diagnostic utility of single-user peroral cholangioscopy in sclerosing cholangitis. Scand J Gastroenterol. 2014;49(10):1237–44.

    Article  PubMed  Google Scholar 

  49. Arnelo U, von Seth E, Bergquist A. Prospective evaluation of the clinical utility of single-operator peroral cholangioscopy in patients with primary sclerosing cholangitis. Endoscopy. 2015;47(8):696–702.

    Article  PubMed  Google Scholar 

  50. Liu R, Cox Rn K, Siddiqui A, Feurer M, Baron T, Adler DG. Peroral cholangioscopy facilitates targeted tissue acquisition in patients with suspected cholangiocarcinoma. Minerva Gastroenterol Dietol. 2014;60(2):127–33.

    CAS  PubMed  Google Scholar 

  51. Meining A, Shah RJ, Slivka A, Pleskow D, Chuttani R, Stevens PD, et al. Classification of probe-based confocal laser endomicroscopy findings in pancreaticobiliary strictures. Endoscopy. 2012;44(3):251–7.

    Article  CAS  PubMed  Google Scholar 

  52. Caillol F, Filoche B, Gaidhane M, Kahaleh M. Refined probe-based confocal laser endomicroscopy classification for biliary strictures: the Paris Classification. Dig Dis Sci. 2013;58(6):1784–9.

    Article  PubMed  Google Scholar 

  53. Slivka A, Gan I, Jamidar P, Costamagna G, Cesaro P, Giovannini M, et al. Validation of the diagnostic accuracy of probe-based confocal laser endomicroscopy for the characterization of indeterminate biliary strictures: results of a prospective multicenter international study. Gastrointest Endosc. 2015;81(2):282–90.

    Article  PubMed  Google Scholar 

  54. Tyberg A, Xu MM, Gaidhane M, Kahaleh M. Second generation optical coherence tomography: preliminary experience in pancreatic and biliary strictures. Dig Liver Dis. 2018;50(11):1214–7.

    Article  PubMed  Google Scholar 

  55. Arvanitakis M, Hookey L, Tessier G, Demetter P, Nagy N, Stellke A, et al. Intraductal optical coherence tomography during endoscopic retrograde cholangiopancreatography for investigation of biliary strictures. Endoscopy. 2009;41(8):696–701.

    Article  CAS  PubMed  Google Scholar 

  56. Meister T, Heinzow HS, Woestmeyer C, Lenz P, Menzel J, Kucharzik T, et al. Intraductal ultrasound substantiates diagnostics of bile duct strictures of uncertain etiology. World J Gastroenterol. 2013;19(6):874–81.

    Article  PubMed  PubMed Central  Google Scholar 

  57. von Seth E, Arnelo U, Enochsson L, Bergquist A. Primary sclerosing cholangitis increases the risk for pancreatitis after endoscopic retrograde cholangiopancreatography. Liver Int. 2015;35(1):254–62.

    Article  Google Scholar 

  58. Enns R, Eloubeidi MA, Mergener K, Jowell PS, Branch MS, Baillie J. Predictors of successful clinical and laboratory outcomes in patients with primary sclerosing cholangitis undergoing endoscopic retrograde cholangiopancreatography. Can J Gastroenterol. 2003;17(4):243–8.

    Article  CAS  PubMed  Google Scholar 

  59. Etzel JP, Eng SC, Ko CW, Lee SD, Saunders MD, Tung BY, et al. Complications after ERCP in patients with primary sclerosing cholangitis. Gastrointest Endosc. 2008;67(4):643–8.

    Article  PubMed  Google Scholar 

  60. Bangarulingam SY, Gossard AA, Petersen BT, Ott BJ, Lindor KD. Complications of endoscopic retrograde cholangiopancreatography in primary sclerosing cholangitis. Am J Gastroenterol. 2009;104(4):855–60.

    Article  PubMed  Google Scholar 

  61. Committee ASoP, Chandrasekhara V, Khashab MA, Muthusamy VR, Acosta RD, Agrawal D, et al. Adverse events associated with ERCP. Gastrointest Endosc. 2017;85(1):32–47.

  62. Committee ASoP, Khashab MA, Chithadi KV, Acosta RD, Bruining DH, Chandrasekhara V, et al. Antibiotic prophylaxis for GI endoscopy. Gastrointest Endosc. 2015;81(1):81–9.

    Article  Google Scholar 

  63. • Othman MO, Guerrero R, Elhanafi S, Davis B, Hernandez J, Houle J, et al. A prospective study of the risk of bacteremia in directed cholangioscopic examination of the common bile duct. Gastrointest Endosc. 2016;83(1):151–7. This prospective study highlights the increased risk of bacteremia during cholangioscopy.

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Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Ave., S.W., Rochester, MN, 55905, USA

    Tarek Sawas MD, Karan Kaura MBBS & Vinay Chandrasekhara MD

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  1. Tarek Sawas MD
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  2. Karan Kaura MBBS
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  3. Vinay Chandrasekhara MD
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Writing of the manuscript: TS, KK, and VC

Guarantor of the article: Dr. Vinay Chandrasekhara

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Correspondence to Vinay Chandrasekhara MD.

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VC: Advisory board member for Interpace Diagnostics and shareholder of Nevakar Corporation

Tarek Sawas declares that he has no conflict of interest. Karan Kaura declares that there is no conflict of interest.

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Sawas, T., Kaura, K. & Chandrasekhara, V. Endoscopic Diagnosis and Therapy in Primary Sclerosing Cholangitis. Curr Treat Options Gastro 18, 353–368 (2020). https://doi.org/10.1007/s11938-020-00293-z

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