The potential role of endoscopic ultrasound in primary sclerosing cholangitis

Advanced endoscopy meets molecular diagnosis of cholangiocarcinomaJournal of HepatologyVol. 78Issue 5PreviewCholangiocarcinoma remains an aggressive and deadly malignancy that is often diagnosed late. Intrinsic tumour characteristics and the growth pattern of cancer cells contribute to the challenges of diagnosis and chemoresistance. However, establishing an early and accurate diagnosis, and in some instances identifying targetable changes, has the potential to impact survival. Primary sclerosing cholangitis, a chronic cholangiopathy prodromal to the development of a minority of cholangiocarcinomas, poses a particular diagnostic challenge. Full-Text PDF All authors have no proprietary, financial, professional, or other personal interest of any nature or kind in any product, service, and/or company that could be construed as influencing the position presented in, or the review of this manuscript. All authors contributed to the manuscript editing and had full control over the preparation of the manuscript. All authors have read and agreed to the published version of the manuscript. We read with interest the recent manuscript by Cadamuro 1Cadamuro M. Al-Taee A. Gonda T.A. Advanced endoscopy meets molecular diagnosis of cholangiocarcinoma.J Hepatol. 2023 Feb 4; (00080-6): S0168-8278PubMed Google Scholar in which molecular mechanisms and diagnostic approaches of perihilar/distal cholangiocarcinoma (p/dCCA), are extensively discussed. Due to the poor prognosis of CCA, an early diagnosis remains the first important aspect in these patients. In the article, while in the diagnostic approach of sporadic indeterminate biliary strictures, the endoscopy ultrasound with fine needle tissue acquisition (EUS FNA/FNB) together with endoscopic retrograde cholangiopancreatography (ERCP) is proposed, in patients affected by PSC (primary sclerosing cholangitis) only ERCP with tissue sampling (brushing and/or biopsy) is discussed in case of relevant or possible dominant strictures. In the setting of the sporadic CCA, the recent Italian clinical guidelines suggest EUS with FNA/FNB as the first approach to obtain a definitive diagnosis of p/dCCA 2Alvaro D. Cholangiocarcinoma Working GroupItalian Clinical Practice Guidelines on Cholangiocarcinoma - Part I: Classification, diagnosis and staging.Dig Liver Dis. 2020 Nov; 52: 1282-1293https://doi.org/10.1016/j.dld.2020.06.045Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar. Notably, a systematic review and meta-analysis found that EUS was superior to ERCP for the diagnosis of malignancy in biliary stricture, and a prospective comparative study showed a higher sensitivity of EUS-FNA in comparison with ERCP with brushing and/or biopsy in diagnosing malignant strictures 3Moura D.T.H. de Moura E.G.H. Matuguma S.E. Dos Santos M.E. Moura E.T.H. Baracat F.I. Artifon E. Cheng S. Bernardo W.M. Chacon D. Tanigawa R. Jukemura J. EUS-FNA versus ERCP for tissue diagnosis of suspect malignant biliary strictures: a prospective comparative study.Endosc Int Open. 2018 Jun; 6: E769-E777Crossref PubMed Google Scholar. Actually, the current guidelines of PSC consider EUS in the diagnostic workup of dCCA 4European Association for the Study of the LiverEASL Clinical Practice Guidelines on sclerosing cholangitis.J Hepatol. 2022 Sep; 77: 761-806Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar,5Bowlus C.L. Arrivé L. Bergquist A. Deneau M. Forman L. Ilyas S.I. Lunsford K.E. Martinez M. Sapisochin G. Shroff R. Tabibian J.H. Assis D.N. AASLD practice guidance on primary sclerosing cholangitis and cholangiocarcinoma.Hepatology. 2023 Feb 1; 77: 659-702Crossref PubMed Scopus (21) Google Scholar and suggest to avoid tissue sampling in pCCA in possible liver transplantation (LT) candidates. Data on EUS in CCA arising in PSC patients are scarce and the main concern is about cancer seeding in patients potentially candidates for LT. Concerning this point, some case reports described tumor seeding from EUS-FNA 6Facciorusso A. Crinò S.F. Gkolfakis P. Ramai D. Mangiavillano B. Londoño Castillo J. Chandan S. Mohan B.P. D'Errico F. Decembrino F. Domislovic V. Anderloni A. Needle Tract Seeding after Endoscopic Ultrasound Tissue Acquisition of Pancreatic Lesions: A Systematic Review and Meta-Analysis.Diagnostics (Basel). 2022 Aug 31; 12: 2113Crossref PubMed Scopus (3) Google Scholar. However, these studies are retrospective and often consider together the EUS approach with the percutaneous one, which is demonstrated to carry a greater risk of tumor seeding. It is also to be considered that several novel methods and devices have been introduced that may reduce the risk of seeding by minimizing the number of FNA/FNB passes and improving the simple acquisition technique. Notably, a retrospective study showed that preoperative EUS-FNA does not affect the survival or progression-free survival of patients with CCA 7El Chafic A.H. DeWitt J. Leblanc J.K. I El Hajj I. Cote G. House M.G. Sherman S. McHenry L. Pitt H.A. Johnson C. et al.Impact of preoperative endoscopic ultrasound-guided fine needle aspiration on postoperative recurrence and survival in cholangiocarcinoma patients.Endoscopy. 2013; 45: 883-889Crossref PubMed Scopus (66) Google Scholar, but no prospective study exists regarding this issue. It is important to underline that cancer seeding is relevant mainly in patients with pCCA candidate to resection or transplantation because of peritoneal dissemination, while in dCCA, the planned surgery (the Whipple’s resection) includes removing part of the duodenum and therefore the risk of seeding is less concerning. EUS is also useful in determining regional lymph-node (LN) involvement even with superiority to computed tomography or magnetic resonance images 8Malikowski T. Levy M.J. Gleeson F.C. Storm A.C. Vargas E.J. Topazian M.D. Abu Dayyeh B.K. Iyer P.G. Rajan E. Gores G.J. Roberts L.R. Chandrasekhara V. Endoscopic Ultrasound/Fine Needle Aspiration Is Effective for Lymph Node Staging in Patients With Cholangiocarcinoma.Hepatology. 2020 Sep; 72: 940-948Crossref PubMed Scopus (25) Google Scholar; this aspect being crucial in evaluating the resectability and LT indication. Thus, although there are no identified LN morphologic criteria to accurately predict the presence of nodal involvement, in case of suspected LN metastasis, EUS tissue sampling may be considered. Considering the high accuracy of EUS-FNA/FNB in the diagnosis of malignancy in the workup of the biliary stricture, we think that this tool may be considered also in PSC patients in selected clinical scenarios, such as PSC patients with suspected dCCA, and those with suspected lymph-node metastasis. In cases of obstructive jaundice where drainage with ERCP is essential, a EUS-ERCP combined session may be considered due to the higher accuracy of this strategy. Another interesting and not yet explored field is represented by morphologic evaluation of the biliary tree by EUS in suspected PSC patients 9Lutz H.H. Wasmuth H.E. Streetz K. Tacke F. Koch A. Luedde T. Trautwein C. Tischendorf Endoscopic ultrasound as an early diagnostic tool for primary sclerosing cholangitis: a prospective pilot study.J.Endoscopy. 2012 Oct; 44: 934-939Crossref PubMed Scopus (24) Google Scholar, and the possibility to find ultrasound bile ducts’ modifications that may predict tumor appearance. Indeed, it has been recently demonstrated that PSC tissue alterations involve diffusely the wall of the large intra and extrahepatic bile ducts 10Carpino G. Cardinale V. Folseraas T. Overi D. Grzyb K. Costantini D. Berloco P.B. Di Matteo S. Karlsen T.H. Alvaro D. Gaudio E. Neoplastic Transformation of the Peribiliary Stem Cell Niche in Cholangiocarcinoma Arisen in Primary Sclerosing Cholangitis.Hepatology. 2019 Feb; 69 (Epub 2019 Jan 4): 622-638https://doi.org/10.1002/hep.30210Crossref PubMed Scopus (42) Google Scholar. Carcinogenesis in PSC is a multistep process, and notably is a diffuse process along the intrahepatic large and extrahepatic bile ducts, with tumor appearance anticipated by typical morphological modifications of duct wall which resulted in progressive thickening associated with inflammation and proliferation of peribiliary gland cells (field cancerization) 10Carpino G. Cardinale V. Folseraas T. Overi D. Grzyb K. Costantini D. Berloco P.B. Di Matteo S. Karlsen T.H. Alvaro D. Gaudio E. Neoplastic Transformation of the Peribiliary Stem Cell Niche in Cholangiocarcinoma Arisen in Primary Sclerosing Cholangitis.Hepatology. 2019 Feb; 69 (Epub 2019 Jan 4): 622-638https://doi.org/10.1002/hep.30210Crossref PubMed Scopus (42) Google Scholar. Therefore, EUS potentially may evaluate diffuse changes of bile ducts, primarily the wall of the ducts, defining those subjects with a suspected PSC, and PSC patients with characteristics worthy of close follow-up or further intervention. Moreover, EUS findings suggestive of field cancerization can be highly informative to plan the surgical approach in LT in PSC in order to prevent CCA recurrence 4European Association for the Study of the LiverEASL Clinical Practice Guidelines on sclerosing cholangitis.J Hepatol. 2022 Sep; 77: 761-806Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar. In conclusion, EUS represent a promising diagnostic tool in PSC patients with indeterminate distal biliary stricture and those with a suspicion of regional LN involvement. A detailed morphological study of the extrahepatic biliary tract could open up interesting future scenarios for the early diagnosis of PSC and PSC/CCA. Prospective studies analyzing the peritoneal seeding risk and the EUS correlates of PSC and of the field cancerization-associated tissue modifications in PSC are needed to better address the issue of the role of EUS in PSC. Further technological implementations, such as contrast-enhanced EUS or the application of elastography to evaluate large intra and extrahepatic bile duct could be complementary for investigating PSC along its progression. The authors would like to thank Prof. Guido Carpino for the revision of the manuscript, critical discussion, and support.