Advertisement

Diagnosis and Treatment: ERCP in PSC

  • Nandakumar SrinivasanEmail author
  • Richard Kozarek
Chapter

Abstract

Primary sclerosing cholangitis (PSC) is a chronic progressive cholestatic disease characterized by inflammatory destruction and fibrosis of both intra- and extra-hepatic bile ducts. Seen primarily in patients with underlying inflammatory bowel disease who have an increased risk of colorectal cancer, the most feared biliary complication of PSC is cholangiocarcinoma. Endoscopic cholangiopancreatography (ERCP) is a very useful diagnostic and therapeutic tool in the management of PSC and cholangiocarcinoma.

In this chapter we review our current understanding of this complex biliary disorder, which includes the risk factors, pathogenesis, differential diagnosis, overlap syndromes, complications including cholangiocarcinoma, the role of ERCP in the diagnosis and management of complications related to PSC/cholangiocarcinoma, and the role of other noninvasive techniques such as magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasound (EUS) in the diagnosis of PSC.

Keywords

Primary sclerosing cholangitis PSC Cholangiocarcinoma Endoscopic cholangiopancreatography ERCP Magnetic resonance cholangiopancreatography MRCP Secondary sclerosing cholangitis Autoimmune disease Cholestatic liver disease Inflammatory bowel disease 

Supplementary material

318160_1_En_22_MOESM1_ESM.mp4 (7.2 mb)
Video 22.1 This 51-year-old patient has inactive chronic ulcerative colitis and progressive cholestasis from primary sclerosing cholangitis. Diagnostic ERCP demonstrates multiple intra- and extra-hepatic strictures and stones treated with a small biliary sphincterotomy, stricture dilation, stone extraction, brush cytology, and placement of short-term right and left hepatic duct stents. Bilirubin fell from 14 mg/dL to 1.0 and alkaline phosphatase levels decreased threefold for >1 year post-endoscopic treatment. (WMV 18638 kb)
Video 22.2

Reticular pattern of biliary epithelium manifest by thick dark bands and clumps in a patient with cholangicarcinoma as visualized with confocal endomicroscopy (Cellvizio, Mauna Kea Technologies, Paris, France). Thick white bands are vessels. Image courtesy of Ian Gan MD, Virginia Mason Medical Center. (WMV 18638 kb)

References

  1. 1.
    Eaton JE, Talwalkar JA, Lazaridis KN, Gores GJ, Lindor KD. Pathogenesis of primary sclerosing cholangitis and advances in diagnosis and management. Gastroenterology. 2013;145(3):521–36.PubMedCrossRefGoogle Scholar
  2. 2.
    Gossard AA, Lindor KD. A 42-year-old woman with a new diagnosis of sclerosing cholangitis. Clin Gastroenterol Hepatol. 2012;10(6):593–7.PubMedCrossRefGoogle Scholar
  3. 3.
    Majoie CB, Reeders JW, Sanders JB, Huibregtse K, Jansen PL. Primary sclerosing cholangitis: a modified classification of cholangiographic findings. AJR Am J Roentgenol. 1991;157(3):495–7.PubMedCrossRefGoogle Scholar
  4. 4.
    Etzel JP, Eng SC, Ko CW, Lee SD, Saunders MD, Tung BY, Kimmey MB, Kowdley KV. Complications after ERCP in patients with primary sclerosing cholangitis. Gastrointest Endosc. 2008;67(4):643–8.PubMedCrossRefGoogle Scholar
  5. 5.
    Bambha K, Kim WR, Talwalkar J, Torgerson H, Benson JT, Therneau TM, Loftus Jr EV, Yawn BP, Dickson ER, Melton 3rd LJ. Incidence, clinical spectrum, and outcomes of primary sclerosing cholangitis in a United States community. Gastroenterology. 2003;125(5):1364–9.PubMedCrossRefGoogle Scholar
  6. 6.
    Singh S, Talwalkar JA. Primary sclerosing cholangitis: diagnosis, prognosis, and management. Clin Gastroenterol Hepatol. 2013;11(8):898–907.PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Molodecky NA, Kareemi H, Parab R, Barkema HW, Quan H, Myers RP, Kaplan GG. Incidence of primary sclerosing cholangitis: a systematic review and meta-analysis. Hepatology. 2011;53(5):1590–9.PubMedCrossRefGoogle Scholar
  8. 8.
    Farrant JM, Hayllar KM, Wilkinson ML, Karani J, Portmann BC, Westaby D, Williams R. Natural history and prognostic variables in primary sclerosing cholangitis. Gastroenterology. 1991;100(6):1710–7.PubMedGoogle Scholar
  9. 9.
    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.PubMedCrossRefGoogle Scholar
  10. 10.
    Kingham JG, Kochar N, Gravenor MB. Incidence, clinical patterns, and outcomes of primary sclerosing cholangitis in South Wales, United Kingdom. Gastroenterology. 2004;126(7):1929–30.PubMedCrossRefGoogle Scholar
  11. 11.
    Boberg KM, Aadland E, Jahnsen J, Raknerud N, Stiris M, Bell H. Incidence and prevalence of primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis in a Norwegian population. Scand J Gastroenterol. 1998;33(1):99–103.PubMedCrossRefGoogle Scholar
  12. 12.
    Wiesner RH, Grambsch PM, Dickson ER, Ludwig J, MacCarty RL, Hunter EB, Fleming TR, Fisher LD, Beaver SJ, LaRusso NF. Primary sclerosing cholangitis: natural history, prognostic factors and survival analysis. Hepatology. 1989;10(4):430–6.PubMedCrossRefGoogle Scholar
  13. 13.
    Tischendorf JJ, Hecker H, Krüger 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.PubMedCrossRefGoogle Scholar
  14. 14.
    Karlsen TH, Franke A, Melum E, Kaser A, Hov JR, Balschun T, Lie BA, Bergquist A, et al. Genome-wide association analysis in primary sclerosing cholangitis. Gastroenterology. 2010;138(3):1102–11.PubMedCrossRefGoogle Scholar
  15. 15.
    Bergquist A, Lindberg G, Saarinen S, Broomé U. Increased prevalence of primary sclerosing cholangitis among first-degree relatives. J Hepatol. 2005;42(2):252–6.PubMedCrossRefGoogle Scholar
  16. 16.
    Mitchell SA, Grove J, Spurkland A, Boberg KM, Fleming KA, Day CP, Schrumpf E, Chapman RW, European Study Group of Primary Sclerosing Cholangitis. Association of the tumour necrosis factor alpha −308 but not the interleukin 10–627 promoter polymorphism with genetic susceptibility to primary sclerosing cholangitis. Gut. 2001;49(2):288–94.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Satsangi J, Chapman RW, Haldar N, Donaldson P, Mitchell S, Simmons J, Norris S, Marshall SE, Bell JI, Jewell DP, Welsh KI. A functional polymorphism of the stromelysin gene (MMP-3) influences susceptibility to primary sclerosing cholangitis. Gastroenterology. 2001;121(1):124–30.PubMedCrossRefGoogle Scholar
  18. 18.
    Yang X, Cullen SN, Li JH, Chapman RW, Jewell DP. Susceptibility to primary sclerosing cholangitis is associated with polymorphisms of intercellular adhesion molecule-1. J Hepatol. 2004;40(3):375–9.PubMedCrossRefGoogle Scholar
  19. 19.
    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.PubMedCrossRefGoogle Scholar
  20. 20.
    Rosen CB, Nagorney DM, Wiesner RH, Coffey Jr RJ, LaRusso NF. Cholangiocarcinoma complicating primary sclerosing cholangitis. Ann Surg. 1991;213(1):21–5.PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Vera A, Gunson BK, Ussatoff V, et al. Colorectal cancer in patients with inflammatory bowel disease after liver transplantation for primary sclerosing cholangitis. Transplantation. 2003;75:1983–8.PubMedCrossRefGoogle Scholar
  22. 22.
    Talwalkar JA, Lindor KD. Primary sclerosing cholangitis. Inflamm Bowel Dis. 2005;11(1):62–72.PubMedCrossRefGoogle Scholar
  23. 23.
    European Association for the Study of the Liver. EASL clinical practice guidelines: management of cholestatic liver diseases. J Hepatol. 2009;51(2):237–67.CrossRefGoogle Scholar
  24. 24.
    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.PubMedGoogle Scholar
  25. 25.
    Chapman R, Fevery J, Kalloo A, Nagorney DM, Boberg KM, Shneider B, Gores GJ, American Association for the Study of Liver Diseases. Diagnosis and management of primary sclerosing cholangitis. Hepatology. 2010;51(2):660–78.PubMedCrossRefGoogle Scholar
  26. 26.
    Lee YM, Kaplan MM. Primary sclerosing cholangitis. N Engl J Med. 1995;332(14):924–33.PubMedCrossRefGoogle Scholar
  27. 27.
    Loperfido S, Angelini G, Benedetti G, Chilovi F, Costan F, De Berardinis F, De Bernardin M, Ederle A, Fina P, Fratton A. Major early complications from diagnostic and therapeutic ERCP: a prospective multicenter study. Gastrointest Endosc. 1998;48(1):1–10.PubMedCrossRefGoogle Scholar
  28. 28.
    MacCarty RL, LaRusso NF, Wiesner RH, Ludwig J. Primary sclerosing cholangitis: findings on cholangiography and pancreatography. Radiology. 1983;149(1):39–44.PubMedCrossRefGoogle Scholar
  29. 29.
    Parlak E, Ciçek B, Dişibeyaz S, Köksal AS, Sahin B. An endoscopic finding in patients with primary sclerosing cholangitis: retraction of the main duodenal papilla into the duodenum wall. Gastrointest Endosc. 2007;65(3):532–6.PubMedCrossRefGoogle Scholar
  30. 30.
    Lutz HH, Wasmuth HE, Streetz K, Tacke F, Koch A, Luedde T, Trautwein C, Tischendorf JJ. Endoscopic ultrasound as an early diagnostic tool for primary sclerosing cholangitis: a prospective pilot study. Endoscopy. 2012;44(10):934–9.PubMedCrossRefGoogle Scholar
  31. 31.
    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.PubMedCrossRefGoogle Scholar
  32. 32.
    Hossary SH, Zytoon AA, Eid M, Hamed A, Sharaan M, Ebrahim AA. MR cholangiopancreatography of the pancreas and biliary system: a review of the current applications. Curr Probl Diagn Radiol. 2014;43(1):1–13.PubMedCrossRefGoogle Scholar
  33. 33.
    Rossi G, Sciveres M, Maruzzelli L, Curcio G, Riva S, Traina M, Tuzzolino F, Luca A, Gridelli B, Maggiore G. Diagnosis of sclerosing cholangitis in children: blinded, comparative study of magnetic resonance versus endoscopic cholangiography. Clin Res Hepatol Gastroenterol. 2013;37(6):596–601.PubMedCrossRefGoogle Scholar
  34. 34.
    Moff SL, Kamel IR, Eustace J, Lawler LP, Kantsevoy S, Kalloo AN, Thuluvath PJ. Diagnosis of primary sclerosing cholangitis: a blinded comparative study using magnetic resonance cholangiography and endoscopic retrograde cholangiography. Gastrointest Endosc. 2006;64(2):219–23.PubMedCrossRefGoogle Scholar
  35. 35.
    Gotthardt DN, Rudolph G, Klöters-Plachky P, Kulaksiz H, Stiehl A. Endoscopic dilation of dominant stenoses in primary sclerosing cholangitis: outcome after long-term treatment. Gastrointest Endosc. 2010;71(3):527–34.PubMedCrossRefGoogle Scholar
  36. 36.
    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.PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.
    Hammel P, Couvelard A, O'Toole D, Ratouis A, Sauvanet A, Fléjou JF, Degott C, Belghiti J, Bernades P, Valla D, Ruszniewski P, Lévy P. Regression of liver fibrosis after biliary drainage in patients with chronic pancreatitis and stenosis of the common bile duct. N Engl J Med. 2001;344(6):418–23.PubMedCrossRefGoogle Scholar
  38. 38.
    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.PubMedCrossRefGoogle Scholar
  39. 39.
    Stiehl A, Rudolph G, Klöters-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.PubMedCrossRefGoogle Scholar
  40. 40.
    van Milligen de Wit AW, van Bracht J, Rauws EA, Jones EA, Tytgat GN, Huibregtse K. Endoscopic stent therapy for dominant extrahepatic bile duct strictures in primary sclerosing cholangitis. Gastrointest Endosc. 1996;44((3):293–9.PubMedCrossRefGoogle Scholar
  41. 41.
    Gaing AA, Geders JM, Cohen SA, Siegel JH. Endoscopic management of primary sclerosing cholangitis: review, and report of an open series. Am J Gastroenterol. 1993;88(12):2000–8.PubMedGoogle Scholar
  42. 42.
    Lee JG, Schutz SM, England RE, Leung JW, Cotton PB. Endoscopic therapy of sclerosing cholangitis. Hepatology. 1995;21(3):661–7.PubMedGoogle Scholar
  43. 43.
    Wagner S, Gebel M, Meier P, Trautwein C, Bleck J, Nashan B, Manns MP. Endoscopic management of biliary tract strictures in primary sclerosing cholangitis. Endoscopy. 1996;28(7):546–51.PubMedCrossRefGoogle Scholar
  44. 44.
    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.PubMedGoogle Scholar
  45. 45.
    Cotton PB, Garrow DA, Gallagher J, Romagnuolo J. Risk factors for complications after ERCP: a multivariate analysis of 11,497 procedures over 12 years. Gastrointest Endosc. 2009;70(1):80–8.PubMedCrossRefGoogle Scholar
  46. 46.
    Ismail S, Kylänpää L, Mustonen H, Halttunen J, Lindström O, Jokelainen K, Udd M, Färkkilä M. Risk factors for complications of ERCP in primary sclerosing cholangitis. Endoscopy. 2012;44(12):1133–8.PubMedCrossRefGoogle Scholar
  47. 47.
    Björnsson E, Olsson R, Bergquist A, Lindgren S, Braden B, Chapman RW, Boberg KM, Angulo P. The natural history of small-duct primary sclerosing cholangitis. Gastroenterology. 2008;134(4):975–80.PubMedCrossRefGoogle Scholar
  48. 48.
    Gregorio GV, Portmann B, Karani J, Harrison P, Donaldson PT, Vergani D, Mieli-Vergani G. Autoimmune hepatitis/sclerosing cholangitis overlap syndrome in childhood: a 16-year prospective study. World J Gastroenterol. 2008;14(21):3368–73.CrossRefGoogle Scholar
  49. 49.
    Kaya M, Angulo P, Lindor KD. Overlap of autoimmune hepatitis and primary sclerosing cholangitis: an evaluation of a modified scoring system. J Hepatol. 1999;31(5):929–38.CrossRefGoogle Scholar
  50. 50.
    Rust C, Beuers U. Overlap syndromes among autoimmune liver diseases. World J Gastroenterol. 2008;14(21):3368–73.PubMedCentralPubMedCrossRefGoogle Scholar
  51. 51.
    Boonstra K, Culver EL, de Buy Wenniger LM, van Heerde MJ, van Erpecum KJ, Poen AC, van Nieuwkerk CM, Spanier BW, Witteman BJ, Tuynman HA, van Geloven N, van Buuren H, Chapman RW, Barnes E, Beuers U, Ponsioen CY. Serum IgG4 and IgG1 for distinguishing IgG4-associated cholangitis from primary sclerosing cholangitis. Hepatology. 2013;21.Google Scholar
  52. 52.
    Ghazale A, Chari ST, Zhang L, Smyrk TC, Takahashi N, Levy MJ, Topazian MD, Clain JE, Pearson RK, Petersen BT, Vege SS, Lindor K, Farnell MB. Immunoglobulin G4-associated cholangitis: clinical profile and response to therapy. Gastroenterology. 2008;134(3):706–15.PubMedCrossRefGoogle Scholar
  53. 53.
    Mendes FD, Jorgensen R, Keach J, Katzmann JA, Smyrk T, Donlinger J, Chari S, Lindor KD. Elevated serum IgG4 concentration in patients with primary sclerosing cholangitis. Am J Gastroenterol. 2006;101(9):2070–5.PubMedCrossRefGoogle Scholar
  54. 54.
    Parhizkar B, Mohammad Alizadeh AH, Asadzadeh Aghdaee H, Malekpour H, Entezari AH. Primary sclerosing cholangitis associated with elevated immunoglobulin-g4: a preliminary study. ISRN Gastroenterol. 2012;2012:325743.PubMedCentralPubMedCrossRefGoogle Scholar
  55. 55.
    Kornfeld D, Ekbom A, Ihre T. Survival and risk of cholangiocarcinoma in patients with primary sclerosing cholangitis. A population-based study. Scand J Gastroenterol. 1997;32(10):1042–5.PubMedCrossRefGoogle Scholar
  56. 56.
    Razumilava N, Gores GJ, Lindor KD. Cancer surveillance in patients with primary sclerosing cholangitis. Hepatology. 2011;54(5):1842–52.PubMedCentralPubMedCrossRefGoogle Scholar
  57. 57.
    Burak K, Angulo P, Pasha TM, Egan K, Petz J, Lindor KD. Incidence and risk factors for cholangiocarcinoma in primary sclerosing cholangitis. Am J Gastroenterol. 2004;99(3):523–6.PubMedCrossRefGoogle Scholar
  58. 58.
    Rizvi S, Gores GJ. Pathogenesis, diagnosis, and management of cholangiocarcinoma. Gastroenterology. 2013;145(6):1215–29.PubMedCrossRefGoogle Scholar
  59. 59.
    DeOliveira ML, Cunningham SC, Cameron JL, Kamangar F, Winter JM, Lillemoe KD, Choti MA, Yeo CJ, Schulick RD. Cholangiocarcinoma: thirty-one-year experience with 564 patients at a single institution. Ann Surg. 2007;245(5):755–62.PubMedCentralPubMedCrossRefGoogle Scholar
  60. 60.
    Deoliveira ML, Schulick RD, Nimura Y, Rosen C, Gores G, Neuhaus P, Clavien PA. New staging system and a registry for perihilar cholangiocarcinoma. Hepatology. 2011;53(4):1363–71.PubMedCrossRefGoogle Scholar
  61. 61.
    Bergquist A, Ekbom A, Olsson R, Kornfeldt D, Lööf L, Danielsson A, Hultcrantz R, Lindgren S, Prytz H, Sandberg-Gertzén H, Almer S, Granath F, Broomé U. Hepatic and extrahepatic malignancies in primary sclerosing cholangitis. J Hepatol. 2002;36(3):321–7.PubMedCrossRefGoogle Scholar
  62. 62.
    Barr Fritcher EG, Voss JS, Jenkins SM, Lingineni RK, Clayton AC, Roberts LR, Halling KC, Talwalkar JA, Gores GJ, Kipp BR. Primary sclerosing cholangitis with equivocal cytology: fluorescence in situ hybridization and serum CA 19–9 predict risk of malignancy. Cancer Cytopathol. 2013;121(12):708–17.PubMedCrossRefGoogle Scholar
  63. 63.
    Govil H, Reddy V, Kluskens L, Treaba D, Massarani-Wafai R, Selvaggi S, Gattuso P. Brush cytology of the biliary tract: retrospective study of 278 cases with histopathologic correlation. Diagn Cytopathol. 2002;26:273–7.PubMedCrossRefGoogle Scholar
  64. 64.
    Harewood GC, Baron TH, Stadheim LM, Kipp BR, Sebo TJ, Salomao DR. Prospective, blinded assessment of factors influencing the accuracy of biliary cytology interpretation. Am J Gastroenterol. 2004;99:1464–9.PubMedCrossRefGoogle Scholar
  65. 65.
    Furmanczyk PS, Grieco VS, Agoff SN. Biliary brush cytology and the detection of cholangiocarcinoma in primary sclerosing cholangitis: evaluation of specific cytomorphologic features and CA19-9 levels. Am J Clin Pathol. 2005;124(3):355–60.PubMedCrossRefGoogle Scholar
  66. 66.
    Lee JG. Brush cytology and the diagnosis of pancreaticobiliary malignancy during ERCP. Gastrointest Endosc. 2006;63:78–80.PubMedCrossRefGoogle Scholar
  67. 67.
    Mahmoudi N, Enns R, Amar J, AlAli J, Lam E, Telford J. Biliary brush cytology: factors associated with positive yields on biliary brush cytology. World J Gastroenterol. 2008;14:569–73.PubMedCentralPubMedCrossRefGoogle Scholar
  68. 68.
    Moreno Luna LE, Kipp B, Halling KC, Sebo TJ, Kremers WK, Roberts LR, Barr Fritcher EG, Levy MJ, Gores GJ. Advanced cytologic techniques for the detection of malignant pancreatobiliary strictures. Gastroenterology. 2006;131(4):1064–72.PubMedCentralPubMedCrossRefGoogle Scholar
  69. 69.
    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.PubMedCrossRefGoogle Scholar
  70. 70.
    Azeem N, Gostout CJ, Knipschield M, Baron TH. Cholangioscopy with narrow-band imaging in patients with primary sclerosing cholangitis undergoing ERCP. Gastrointest Endosc 2013;79(5):773–9 e2.Google Scholar
  71. 71.
    Chen YK, Parsi MA, Binmoeller KF, Hawes RH, Pleskow DK, Slivka A, Haluszka O, Petersen BT, Sherman S, Devière J, Meisner S, Stevens PD, Costamagna G, Ponchon T, Peetermans JA, Neuhaus H. Single-operator cholangioscopy in patients requiring evaluation of bile duct disease or therapy of biliary stones. Gastrointest Endosc. 2011;74(4):805–14.PubMedCrossRefGoogle Scholar
  72. 72.
    Karlsen TH, Boberg KM. Update on primary sclerosing cholangitis. J Hepatol. 2013;59(3):571–82.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Digestive Disease InstituteVirginia Mason Medical CenterSeattleUSA

Personalised recommendations