Are Dominant Strictures in Primary Sclerosing Cholangitis a Risk Factor for Cholangiocarcinoma?
Tóm tắt
Cholangiocarcinoma is a devastating, unpredictable complication of large duct primary sclerosing cholangitis (PSC), which occurs in 5–15% of patients. The aim of this review is to discuss whether dominant strictures (DS) occurring in the larger bile ducts in PSC are a risk factor for the development of cholangiocarcinoma. The development of DS is related to specific genetic polymorphisms affecting the innate immune system and the microbiome. In a recent study, the mean survival of PSC patients with DS was much worse (13.7 years) than for those without a DS (23 years). Survival difference was related to a 26% risk of cholangiocarcinoma, which developed only in those with DS. Half of the patients with cholangiocarcinoma presented within 4 months of the diagnosis of PSC. In another study, the risk of developing cholangiocarcinoma was directly related to the presence of underlying IBD, although this remains controversial. Efforts are being made towards surveying for cholangiocarcinoma including magnetic resonance imaging, endoscopic surveillance and serum tumour markers, but so far, an effective surveillance strategy has not been identified. DS should be treated endoscopically in the setting of symptoms, and there is limited evidence to suggest this may impact protectively on progression to cholangiocarcinoma. It is established that the presence of symptomatic DS occurring in the larger bile ducts in PSC can be the first presentation of cholangiocarcinoma. There is an increasing body of evidence that even when proven to be benign, dominant biliary strictures predispose to the future development of cholangiocarcinoma. Regular surveillance should be targeted at this selected high-risk group of PSC patients.
Tài liệu tham khảo
Hirschfield GM, Karlsen TH, Lindor KD, Adams DH. Primary sclerosing cholangitis. Lancet. 2013;382(9904):1587–99. doi:10.1016/S0140-6736(13)60096-3.
Karlsen TH, Boberg KM. Update on primary sclerosing cholangitis. J Hepatol. 2013;59(3):571–82. doi:10.1016/j.jhep.2013.03.015.
Boonstra K, Weersma RK, van Erpecum KJ, Rauws EA, Spanier BW, Poen AC, et al. Population-based epidemiology, malignancy risk, and outcome of primary sclerosing cholangitis. Hepatology. 2013;58(6):2045–55. doi:10.1002/hep.26565.
Bergquist A, Ekbom A, Olsson R, Kornfeldt D, Loof L, Danielsson A, et al. Hepatic and extrahepatic malignancies in primary sclerosing cholangitis. J Hepatol. 2002;36(3):321–7.
Bjornsson E, Olsson R, Bergquist A, Lindgren S, Braden B, Chapman RW, et al. The natural history of small-duct primary sclerosing cholangitis. Gastroenterology. 2008;134(4):975–80. doi:10.1053/j.gastro.2008.01.042.
Fevery J, Verslype C, Lai G, Aerts R, Van Steenbergen W. Incidence, diagnosis, and therapy of cholangiocarcinoma in patients with primary sclerosing cholangitis. Digestive Diseases & Sciences. 2007;52(11):3123–35.
Claessen MMH, Vleggaar FP, Tytgat KMAJ, Siersema PD, van Buuren HR. High lifetime risk of cancer in primary sclerosing cholangitis. J Hepatol. 50(1):158–64. doi:10.1016/j.jhep.2008.08.013.
Razumilava N, Gores GJ, Lindor KD. Cancer surveillance in patients with primary sclerosing cholangitis. Hepatology. 2011;54(5):1842–52. doi:10.1002/hep.24570.
Williamson KD, Chapman RW. Primary sclerosing cholangitis: a clinical update. Br Med Bull. 2015;114(1):53–64. doi:10.1093/bmb/ldv019.
Darwish Murad S, Kim WR, Harnois DM, Douglas DD, Burton J, Kulik LM, et al. Efficacy of neoadjuvant chemoradiation, followed by liver transplantation, for perihilar cholangiocarcinoma at 12 US centers. Gastroenterology. 2012;143(1):88–98.e3. quiz e14 doi:10.1053/j.gastro.2012.04.008.
Rosen CB, Heimbach JK, Gores GJ. Liver transplantation for cholangiocarcinoma. Transpl Int. 2010;23(7):692–7. doi:10.1111/j.1432-2277.2010.01108.x.
Brandsaeter B, Isoniemi H, Broome U, Olausson M, Backman L, Hansen B, et al. Liver transplantation for primary sclerosing cholangitis; predictors and consequences of hepatobiliary malignancy. J Hepatol. 2004;40(5):815–22. doi:10.1016/j.jhep.2004.01.002.
European Association for the Study of the L. EASL Clinical Practice Guidelines: management of cholestatic liver diseases. J Hepatol. 2009;51(2):237–67. doi:10.1016/j.jhep.2009.04.009.
•• Chapman MH, Webster GJM, 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. This is a seminal study showing definite correlation between dominant strictures with a poor prognosis and the development of cholangiocarcinoma.
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. doi:10.1016/j.gie.2009.10.041.
Järveläinen HA, Orpana A, Perola M, Savolainen VT, Karhunen PJ, Lindros KO. Promoter polymorphism of the CD14 endotoxin receptor gene as a risk factor for alcoholic liver disease. Hepatology. 2001;33(5):1148–53. doi:10.1053/jhep.2001.24236.
Brun P, Castagliuolo I, Floreani AR, Buda A, Blasone L, Palù G, et al. Increased risk of NASH in patients carrying the C(−159)T polymorphism in the CD14 gene promoter region. Gut. 2006;55(8):1212. doi:10.1136/gut.2006.093336.
Friedrich K, Smit M, Brune M, Giese T, Rupp C, Wannhoff A, et al. CD14 is associated with biliary stricture formation. Hepatology. 2016;64(3):843–52. doi:10.1002/hep.28543.
Folseraas T, Melum E, Rausch P, Juran BD, Ellinghaus E, Shiryaev A, et al. Extended analysis of a genome-wide association study in primary sclerosing cholangitis detects multiple novel risk loci. J Hepatol. 2012;57(2):366–75. doi:10.1016/j.jhep.2012.03.031.
• Rupp C, Friedrich K, Folseraas T, Wannhoff A, Bode KA, Weiss KH, et al. Fut2 genotype is a risk factor for dominant stenosis and biliary candida infections in primary sclerosing cholangitis. Aliment Pharmacol Ther. 2014;39(8):873–82. doi:10.1111/apt.12663. This is an important study showing that genetic factors can affect the biome and biliary infection with the development of cholangiocarcinoma.
Rudolph G, Gotthardt D, Kloters-Plachky P, Kulaksiz H, Rost D, Stiehl A. Influence of dominant bile duct stenoses and biliary infections on outcome in primary sclerosing cholangitis. J Hepatol. 2009;51(1):149–55. doi:10.1016/j.jhep.2009.01.023.
•• Rudolph G, Gotthardt D, Kloeters-Plachky P, Rost D, Kulaksiz H, Stiehl A. In PSC with dominant bile duct stenosis, IBD is associated with an increase of carcinomas and reduced survival. J Hepatol. 2010;53(2):313–7. doi:10.1016/j.jhep.2010.02.030. This is the first study to suggest a link between dominant strictures and cholagiocarcinoma with the presence of associated inflammatory bowel disease.
Janse M, Lamberts LE, Verdonk RC, Weersma RK. IBD is associated with an increase in carcinoma in PSC irrespective of the presence of dominant bile duct stenosis. Journal of hepatology. 57(2):473–4. doi:10.1016/j.jhep.2012.02.034.
Clinical Trials identifier: NCT01398917. Short-term stenting versus balloon dilatation for dominant strictures in primary sclerosing cholangitis. URL: https://clinicaltrials.gov/ct2/show/NCT01398917. Accessed 22/02/2017.
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. doi:10.1002/hep.23294.
Nishihara S, Narimatsu H, Iwasaki H, Yazawa S, Akamatsu S, Ando T, et al. Molecular genetic analysis of the human Lewis histo-blood group system. J Biol Chem. 1994;269(46):29271–8.
•• Rizvi S, Eaton JE, Gores GJ. Primary sclerosing cholangitis as a premalignant biliary tract disease: surveillance and management. Clin Gastroenterol Hepatol. 2015;13(12):2152–65. This is an excellent review of surveillance in PSC.
Boyd S, Mustonen H, Tenca A, Jokelainen K, Arola J, Färkkilä MA. Surveillance of primary sclerosing cholangitis with ERC and brush cytology: risk factors for cholangiocarcinoma. Scand J Gastroenterol. 2017;52(2):242–9. doi:10.1080/00365521.2016.1250281.
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. doi:10.1016/j.gie.2013.09.015.
Van den Hazel S, Wolfhagen F, Van Buuren H, van de Meeberg P, Van Leeuwen D. Prospective risk assessment of endoscopic retrograde cholangiography in patients with primary sclerosing cholangitis. Dutch PSC Study Group. Endoscopy. 2000;32(10):779–82.
Bangarulingam SY, Bjornsson E, Enders F, Barr Fritcher EG, Gores G, Halling KC, et al. Long-term outcomes of positive fluorescence in situ hybridization tests in primary sclerosing cholangitis. Hepatology. 2010;51(1):174–80.
• Quinn KP, Tabibian JH, Lindor KD. Clinical implications of serial versus isolated biliary fluorescence in situ hybridization (FISH) polysomy in primary sclerosing cholangitis. Scand J Gastroenterol. 2017;52(4):377–81. doi:10.1080/00365521.2016.1263681. This is an important study showing that a one-off finding of polysomy may not be associated with increased cholangiocarcioma risk in contrast to serial polysomy
Azeem N, Gostout CJ, Knipschield M, Baron TH. Cholangioscopy with narrow-band imaging in patients with primary sclerosing cholangitis undergoing ERCP. Gastrointest Endosc. 2014;79(5):773–9.e2. doi:10.1016/j.gie.2013.09.017.
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. doi:10.1055/s-0034-1391845.
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. doi:10.1055/s-2006-925257.