Advertisement

AGA Clinical Practice Update on Surveillance for Hepatobiliary Cancers in Patients With Primary Sclerosing Cholangitis: Expert Review

      Description

      The purpose of this clinical practice update is to define key principles in the surveillance of hepatobiliary cancers including cholangiocarcinoma, gallbladder adenocarcinoma, and hepatocellular carcinoma in patients with primary sclerosing cholangitis (PSC).

      Methods

      The recommendations outlined in this expert review are based on available published evidence including observational studies and systematic reviews, and incorporates expert opinion where applicable.

      Best practice advice 1

      Surveillance for cholangiocarcinoma and gallbladder cancer should be considered in all adult patients with PSC regardless of disease stage, especially in the first year after diagnosis and in patients with ulcerative colitis and those diagnosed at an older age.

      Best practice advice 2

      Surveillance for cholangiocarcinoma and gallbladder cancer should include imaging by ultrasound, computed tomography, or magnetic resonance imaging, with or without serum carbohydrate antigen 19-9, every 6 to 12 months

      Best practice advice 3

      Endoscopic retrograde cholangiopancreatography with brush cytology should not be used routinely for surveillance of cholangiocarcinomas in PSC.

      Best practice advice 4

      Cholangiocarcinomas should be investigated by endoscopic retrograde cholangiopancreatography with brush cytology with or without fluorescence in situ hybridization analysis and/or cholangioscopy in PSC patients with worsening clinical symptoms, worsening cholestasis, or a dominant stricture.

      Best practice advice 5

      Fine-needle aspiration of perihilar biliary strictures should be used with caution in PSC patients considered to be liver transplant candidates because of concerns for tumor seeding if the lesion is a cholangiocarcinoma.

      Best practice advice 6

      Surveillance for cholangiocarcinoma should not be performed in PSC patients with small-duct PSCs or those younger than age 20.

      Best practice advice 7

      The decision to perform a cholecystectomy in PSC patients with a gallbladder polyp should be based on the size and growth of the polyp, as well as the clinical status of the patient, with the knowledge of the increased risk of gallbladder cancer in polyps greater than 8 mm.

      Best practice advice 8

      Surveillance for hepatocellular carcinoma in PSC patients with cirrhosis should include ultrasound, computed tomography, or magnetic resonance imaging, with or without α-fetoprotein every 6 months.

      Abbreviations used in this paper:

      CA19-9 (carbohydrate antigen 19-9), CT (computed tomography), ERCP (endoscopic retrograde cholangiopancreatography), FISH (fluorescence in situ hybridization), HCC (hepatocellular carcinoma), IBD (inflammatory bowel disease), MRCP (magnetic resonance cholangiopancreatography), MRI (magnetic resonance imaging), PSC (primary sclerosing cholangitis), US (ultrasound)
      To read this article in full you will need to make a payment
      AGA Member Login
      Login with your AGA username and password.
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Bambha K.
        • Kim W.R.
        • Talwalkar J.
        • et al.
        Incidence, clinical spectrum, and outcomes of primary sclerosing cholangitis in a United States community.
        Gastroenterology. 2003; 125: 1364-1369
        • Toy E.
        • Balasubramanian S.
        • Selmi C.
        • et al.
        The prevalence, incidence and natural history of primary sclerosing cholangitis in an ethnically diverse population.
        BMC Gastroenterol. 2011; 11: 83
        • Lindkvist B.
        • Benito de Valle M.
        • Gullberg B.
        • et al.
        Incidence and prevalence of primary sclerosing cholangitis in a defined adult population in Sweden.
        Hepatology. 2010; 52: 571-577
        • Bowlus C.L.
        • Li C.S.
        • Karlsen T.H.
        • et al.
        Primary sclerosing cholangitis in genetically diverse populations listed for liver transplantation: unique clinical and human leukocyte antigen associations.
        Liver Transpl. 2010; 16: 1324-1330
        • Goldberg D.S.
        • Levy C.
        • Yimam K.
        • et al.
        Primary sclerosing cholangitis is not rare among blacks in a multicenter North American consortium.
        Clin Gastroenterol Hepatol. 2018; 16: 591-593
        • Broome U.
        • Olsson R.
        • Loof L.
        • et al.
        Natural history and prognostic factors in 305 Swedish patients with primary sclerosing cholangitis.
        Gut. 1996; 38: 610-615
        • Ponsioen C.Y.
        • Vrouenraets S.M.
        • Prawirodirdjo W.
        • et al.
        Natural history of primary sclerosing cholangitis and prognostic value of cholangiography in a Dutch population.
        Gut. 2002; 51: 562-566
        • Angulo P.
        • Maor-Kendler Y.
        • Lindor K.D.
        Small-duct primary sclerosing cholangitis: a long-term follow-up study.
        Hepatology. 2002; 35: 1494-1500
        • Boonstra K.
        • Weersma R.K.
        • van Erpecum K.J.
        • et al.
        Population-based epidemiology, malignancy risk, and outcome of primary sclerosing cholangitis.
        Hepatology. 2013; 58: 2045-2055
        • Fumery M.
        • Dulai P.S.
        • Gupta S.
        • et al.
        Incidence, risk factors, and outcomes of colorectal cancer in patients with ulcerative colitis with low-grade dysplasia: a systematic review and meta-analysis.
        Clin Gastroenterol Hepatol. 2017; 15: 665-674 e5
        • Shah S.C.
        • Ten Hove J.R.
        • Castaneda D.
        • et al.
        High risk of advanced colorectal neoplasia in patients with primary sclerosing cholangitis associated with inflammatory bowel disease.
        Clin Gastroenterol Hepatol. 2018; 16: 1106-1113 e3
        • Rizvi S.
        • Eaton J.E.
        • Gores G.J.
        Primary sclerosing cholangitis as a pre-malignant biliary tract disease: surveillance and management.
        Clin Gastroenterol Hepatol. 2015; 13: 2152-2165
        • Weismuller T.J.
        • Trivedi P.J.
        • Bergquist A.
        • et al.
        Patient age, sex, and inflammatory bowel disease phenotype associate with course of primary sclerosing cholangitis.
        Gastroenterology. 2017; 152: 1975-1984.e8
        • Bergquist A.
        • Ekbom A.
        • Olsson R.
        • et al.
        Hepatic and extrahepatic malignancies in primary sclerosing cholangitis.
        J Hepatol. 2002; 36: 321-327
        • Boberg K.M.
        • Bergquist A.
        • Mitchell S.
        • et al.
        Cholangiocarcinoma in primary sclerosing cholangitis: risk factors and clinical presentation.
        Scand J Gastroenterol. 2002; 37: 1205-1211
        • Ali A.H.
        • Tabibian J.H.
        • Nasser-Ghodsi N.
        • et al.
        Surveillance for hepatobiliary cancers in patients with primary sclerosing cholangitis.
        Hepatology. 2018; 67: 2338-2351
        • European Association for the Study of the Liver
        EASL Clinical Practice Guidelines: management of cholestatic liver diseases.
        J Hepatol. 2009; 51: 237-267
        • Sinakos E.
        • Saenger A.K.
        • Keach J.
        • et al.
        Many patients with primary sclerosing cholangitis and increased serum levels of carbohydrate antigen 19-9 do not have cholangiocarcinoma.
        Clin Gastroenterol Hepatol. 2011; 9: 434-439.e1
        • Ballehaninna U.K.
        • Chamberlain R.S.
        Serum CA 19-9 as a biomarker for pancreatic cancer-a comprehensive review.
        Indian J Surg Oncol. 2011; 2: 88-100
        • Nehls O.
        • Gregor M.
        • Klump B.
        Serum and bile markers for cholangiocarcinoma.
        Semin Liver Dis. 2004; 24: 139-154
        • Levy C.
        • Lymp J.
        • Angulo P.
        • et al.
        The value of serum CA 19-9 in predicting cholangiocarcinomas in patients with primary sclerosing cholangitis.
        Dig Dis Sci. 2005; 50: 1734-1740
        • Charatcharoenwitthaya P.
        • Enders F.B.
        • Halling K.C.
        • et al.
        Utility of serum tumor markers, imaging, and biliary cytology for detecting cholangiocarcinoma in primary sclerosing cholangitis.
        Hepatology. 2008; 48: 1106-1117
        • Parra-Robert M.
        • Santos V.M.
        • Canis S.M.
        • et al.
        Relationship between CA 19.9 and the Lewis phenotype: options to improve diagnostic efficiency.
        Anticancer Res. 2018; 38: 5883-5888
        • Wannhoff A.
        • Hov J.R.
        • Folseraas T.
        • et al.
        FUT2 and FUT3 genotype determines CA19-9 cut-off values for detection of cholangiocarcinoma in patients with primary sclerosing cholangitis.
        J Hepatol. 2013; 59: 1278-1284
        • Razumilava N.
        • Gores G.J.
        • Lindor K.D.
        Cancer surveillance in patients with primary sclerosing cholangitis.
        Hepatology. 2011; 54: 1842-1852
        • Lindor K.D.
        • Kowdley K.V.
        • Harrison M.E.
        ACG Clinical Guideline: primary sclerosing cholangitis.
        Am J Gastroenterol. 2015; 110 (quiz 660): 646-659
        • Eaton J.E.
        • Barr Fritcher E.G.
        • Gores G.J.
        • et al.
        Biliary multifocal chromosomal polysomy and cholangiocarcinoma in primary sclerosing cholangitis.
        Am J Gastroenterol. 2015; 110: 299-309
        • Navaneethan U.
        • Njei B.
        • Venkatesh P.G.
        • et al.
        Fluorescence in situ hybridization for diagnosis of cholangiocarcinoma in primary sclerosing cholangitis: a systematic review and meta-analysis.
        Gastrointest Endosc. 2014; 79: 943-950 e3
        • Stiehl A.
        • Rudolph G.
        • Kloters-Plachky P.
        • et al.
        Development of dominant bile duct stenoses in patients with primary sclerosing cholangitis treated with ursodeoxycholic acid: outcome after endoscopic treatment.
        J Hepatol. 2002; 36: 151-156
        • Chapman R.W.
        • Williamson K.D.
        Are dominant strictures in primary sclerosing cholangitis a risk factor for cholangiocarcinoma?.
        Curr Hepatol Rep. 2017; 16: 124-129
        • Sangfelt P.
        • Sundin A.
        • Wanders A.
        • et al.
        Monitoring dominant strictures in primary sclerosing cholangitis with brush cytology and FDG-PET.
        J Hepatol. 2014; 61: 1352-1357
        • Trikudanathan G.
        • Navaneethan U.
        • Njei B.
        • et al.
        Diagnostic yield of bile duct brushings for cholangiocarcinoma in primary sclerosing cholangitis: a systematic review and meta-analysis.
        Gastrointest Endosc. 2014; 79: 783-789
        • Kipp B.R.
        • Barr Fritcher E.G.
        • Pettengill J.E.
        • et al.
        Improving the accuracy of pancreatobiliary tract cytology with fluorescence in situ hybridization: a molecular test with proven clinical success.
        Cancer Cytopathol. 2013; 121: 610-619
        • Salomao M.
        • Gonda T.A.
        • Margolskee E.
        • et al.
        Strategies for improving diagnostic accuracy of biliary strictures.
        Cancer Cytopathol. 2015; 123: 244-252
        • Bowlus C.L.
        • Olson K.A.
        • Gershwin M.E.
        Evaluation of indeterminate biliary strictures.
        Nat Rev Gastroenterol Hepatol. 2016; 13: 28-37
        • Nakazawa T.
        • Naitoh I.
        • Hayashi K.
        • et al.
        Diagnosis of IgG4-related sclerosing cholangitis.
        World J Gastroenterol. 2013; 19: 7661-7670
        • 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: 696-702
        • Kalaitzakis E.
        • Sturgess R.
        • Kaltsidis H.
        • et al.
        Diagnostic utility of single-user peroral cholangioscopy in sclerosing cholangitis.
        Scand J Gastroenterol. 2014; 49: 1237-1244
        • Farrant J.M.
        • Hayllar K.M.
        • Wilkinson M.L.
        • et al.
        Natural history and prognostic variables in primary sclerosing cholangitis.
        Gastroenterology. 1991; 100: 1710-1717
        • Marsh Jr., J.W.
        • Iwatsuki S.
        • Makowka L.
        • et al.
        Orthotopic liver transplantation for primary sclerosing cholangitis.
        Ann Surg. 1988; 207: 21-25
        • Miros M.
        • Kerlin P.
        • Walker N.
        • et al.
        Predicting cholangiocarcinoma in patients with primary sclerosing cholangitis before transplantation.
        Gut. 1991; 32: 1369-1373
        • Nashan B.
        • Tusch G.
        • Schlitt H.J.
        • et al.
        [Liver transplantation in patients with primary sclerosing cholangitis. Determining timing with reference to risk of malignancy].
        Langenbecks Arch Chir Suppl Kongressbd. 1996; 113: 410-412
        • Deneau M.R.
        • El-Matary W.
        • Valentino P.L.
        • et al.
        The natural history of primary sclerosing cholangitis in 781 children: a multicenter, international collaboration.
        Hepatology. 2017; 66: 518-527
        • Hirschfield G.M.
        • Karlsen T.H.
        • Lindor K.D.
        • et al.
        Primary sclerosing cholangitis.
        Lancet. 2013; 382: 1587-1599
        • Sagvand B.T.
        • Edwards K.
        • Shen B.
        Gallbladder polyps in patients with primary sclerosing cholangitis; frequency, risk factors and outcome.
        Gastroenterology. 2018; 154: S1097-S1098
        • van Erp L.
        • Cunningham M.
        • Narasimman M.
        • et al.
        Risk of gall bladder cancer in patients with primary sclerosing cholangitis and gall bladder polyps: an opportunity to revisit the guidelines.
        J Hepatol. 2019; 70: e79
        • Wennmacker S.Z.
        • Lamberts M.P.
        • Di Martino M.
        • et al.
        Transabdominal ultrasound and endoscopic ultrasound for diagnosis of gallbladder polyps.
        Cochrane Database Syst Rev. 2018; 8: CD012233
        • Lou M.W.
        • Hu W.D.
        • Fan Y.
        • et al.
        CT biliary cystoscopy of gallbladder polyps.
        World J Gastroenterol. 2004; 10: 1204-1207
        • Said K.
        • Glaumann H.
        • Bergquist A.
        Gallbladder disease in patients with primary sclerosing cholangitis.
        J Hepatol. 2008; 48: 598-605
        • Lewis J.T.
        • Talwalkar J.A.
        • Rosen C.B.
        • et al.
        Prevalence and risk factors for gallbladder neoplasia in patients with primary sclerosing cholangitis: evidence for a metaplasia-dysplasia-carcinoma sequence.
        Am J Surg Pathol. 2007; 31: 907-913
        • Eaton J.E.
        • Thackeray E.W.
        • Lindor K.D.
        Likelihood of malignancy in gallbladder polyps and outcomes following cholecystectomy in primary sclerosing cholangitis.
        Am J Gastroenterol. 2012; 107: 431-439
        • Chapman R.
        • Fevery J.
        • Kalloo A.
        • et al.
        Diagnosis and management of primary sclerosing cholangitis.
        Hepatology. 2010; 51: 660-678
        • de Valle M.B.
        • Bjornsson E.
        • Lindkvist B.
        Mortality and cancer risk related to primary sclerosing cholangitis in a Swedish population-based cohort.
        Liver Int. 2012; 32: 441-448
        • Zenouzi R.
        • Weismuller T.J.
        • Hubener P.
        • et al.
        Low risk of hepatocellular carcinoma in patients with primary sclerosing cholangitis with cirrhosis.
        Clin Gastroenterol Hepatol. 2014; 12: 1733-1738
        • Heimbach J.K.
        • Kulik L.M.
        • Finn R.S.
        • et al.
        AASLD guidelines for the treatment of hepatocellular carcinoma.
        Hepatology. 2018; 67: 358-380