The Diagnostic Dilemma of Malignant Biliary Strictures

Robert Dorrell, Swati Pawa, Yi Zhou, Neeraj Lalwani, Rishi Pawa, Robert Dorrell, Swati Pawa, Yi Zhou, Neeraj Lalwani, Rishi Pawa

Abstract

The differential diagnosis for biliary strictures is broad. However, the likelihood of malignancy is high. Determining the etiology of a biliary stricture requires a comprehensive physical exam, laboratory evaluation, imaging, and ultimately tissue acquisition. Even then, definitive diagnosis is elusive, and many strictures remain indeterminant in origin. This literary review examines the diagnostic dilemma of biliary strictures and presents innovations in both histochemical and endoscopic techniques that have increased the diagnostic power of differentiating benign and malignant strictures. The field of tissue biopsy is revolutionizing with the advent of free DNA mutation profiling, fluorescence in situ hybridization (FISH), and methionyl t-RNA synthetase 1 (MARS 1), which allow for greater testing sensitivity. Endoscopic ultrasound, endoscopic retrograde cholangiopancreatography (ERCP), cholangioscopy, confocal laser endomicroscopy, and intraductal ultrasound build upon existing endoscopic technology to better characterize strictures that would otherwise be indeterminate in etiology. This review uses recent literature to insert innovative technology into the traditional framework of diagnostic methods for malignant biliary strictures.

Keywords: cholangioscopy; confocal laser endomicroscopy; endoscopic retrograde cholangiopancreatography; endoscopic ultrasound; fine-needle aspiration and biopsy; hepatobiliary malignancy; intraductal ultrasound; malignant biliary stricture; pancreatic cancer.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The Bismuth–Corlette classification is a system for characterizing hilar strictures. Type I is limited to the common hepatic duct, below the main confluence of the hepatic ducts. Type II involves the confluence of the left and right hepatic ducts. Type IIIa involves the main hepatic confluence and extends to the bifurcation of the right hepatic duct. Type IIIb involves the main hepatic confluence and extends to the bifurcation of the left hepatic duct. Type IV involves the main, right, and left hepatic confluence.
Figure 2
Figure 2
A,B: Axial contrast computed tomography (CT) shows enhancing intraductal polypoid mass consistent with intraductal cholangiocarcinoma (arrow); C: The circle demonstrates a T2W hypointense lesion found on magnetic resonance cholangiopancreatography (MRCP); D: Postcontrast MR showing an incidentally found subtle mural thickening of the gallbladder fundus later diagnosed as synchronous gallbladder carcinoma.
Figure 3
Figure 3
A: Axial contrast-enhanced CT shows enhancing dilated common duct (arrow); B: there is abrupt cutoff of the common duct and there is diffuse mural thickening and enhancement (arrow); C: The circle demonstrates an infiltrative mass in the distal duct found on coronal CT; D: endoscopic retrograde cholangiopancreatography (ERCP) shows a short-segment tight stricture corresponding to the mass. Biopsy confirmed cholangiocarcinoma.
Figure 4
Figure 4
A: Axial arterial phase CT shows dilated intrahepatic ducts and a hypodense mass (arrow) at the hilum; B,C: venous phase images show enhancement of the mass. This signifies excessive fibrous stroma in the tumor and is consistent with cholangiocarcinoma.
Figure 5
Figure 5
A–C: CT shows a pancreatic head mass with central necrosis (circle, C). Additional findings include no calcifications to support underlying chronic pancreatitis, no ductal dilatation, peripancreatic fat planes are not maintained (blue arrow, A) and superior mesenteric artery (SMA) (red arrow, A)/superior mesenteric vein (SMV) (yellow arrow, A) ratio is ≥ 1. The gastroduodenal artery (green arrow, B) is encased by the mass. Dilated common bile duct (star, C). Overall, there are at least three signs suggesting the diagnosis of malignancy.
Figure 6
Figure 6
ERCP with brushings and resultant cytology. A: Cholangiography showing distal bile duct stricture with upstream ductal dilatation. B: Balloon dilation of distal bile duct stricture. C: Brushings obtained from distal bile duct stricture during ERCP. D: Plastic stent placed in bile duct across stricture for biliary drainage. E: Brush cytology showed biliary tract adenocarcinoma. The group shows loss of polarity, irregularly spaced nuclei. The nuclei are angulated and pointed with subtle grooves and folding. Small nucleoli are present in the cells (Papanicolaou stain).
Figure 7
Figure 7
A: Cholangioscopy revealing hilar stricture with irregular mucosa and neovascularization. B: Stricture sampling with SpyBite biopsy forceps.
Figure 8
Figure 8
A: Endoscopic ultrasound (EUS)-guided fine-needle aspiration of a pancreatic head mass. B: The malignant cells are crowded and overlapping. The nuclei are enlarged and show nuclear size variation in a range of 1:3. (FNA, Papanicolaou stain).
Figure 9
Figure 9
A: Malignant glands admixed with normal pancreatic parenchyma (core biopsy, H&E stain). B: On high power, the tumor cells form solid nest with focal glandular formation. There is nuclear enlargement and irregularity, abnormal chromatin, and prominent nucleoli (core biopsy, H&E stain).

References

    1. Tummala P., Munigala S., Eloubeidi M.A., Agarwal B. Patients with obstructive jaundice and biliary stricture±mass lesion on imaging: Prevalence of malignancy and potential role of EUS-FNA. J. Clin. Gastroenterol. 2013;47:532–537. doi: 10.1097/MCG.0b013e3182745d9f.
    1. Ballinger A., McHugh M., Catnach S., Alstead E., Clark M. Symptom relief and quality of life after stenting for malignant bile duct obstruction. Gut. 1994;35:467–470. doi: 10.1136/gut.35.4.467.
    1. Boulay B.R., Birg A. Malignant biliary obstruction: From palliation to treatment. World J. Gastrointest. Oncol. 2016;8:498. doi: 10.4251/wjgo.v8.i6.498.
    1. Viesca M.F.Y., Arvanitakis M. Early Diagnosis And Management Of Malignant Distal Biliary Obstruction: A Review On Current Recommendations And Guidelines. Clin. Exp. Gastroenterol. 2019;12:415. doi: 10.2147/CEG.S195714.
    1. Welzel T.M., Graubard B.I., El–Serag H.B., Shaib Y.H., Hsing A.W., Davila J.A., McGlynn K.A. Risk factors for intrahepatic and extrahepatic cholangiocarcinoma in the United States: A population-based case-control study. Clin. Gastroenterol. Hepatol. 2007;5:1221–1228. doi: 10.1016/j.cgh.2007.05.020.
    1. Kapoor B.S., Mauri G., Lorenz J.M. Management of biliary strictures: State-of-the-art review. Radiology. 2018;289:590–603. doi: 10.1148/radiol.2018172424.
    1. Garcea G., Ngu W., Neal C.P., Dennison A.R., Berry D.P. Bilirubin levels predict malignancy in patients with obstructive jaundice. HPB. 2011;13:426–430. doi: 10.1111/j.1477-2574.2011.00312.x.
    1. Hayat J., Loew C., Asrress K., McIntyre A., Gorard D. Contrasting liver function test patterns in obstructive jaundice due to biliary structures and stones. Qjm. 2005;98:35–40. doi: 10.1093/qjmed/hci004.
    1. Thomasset S.C., Saunders D., Holland A., Dennison A.R., Garcea G. Malignant biliary strictures in patients with a normal bilirubin and/or normal liver enzymes. HPB. 2015;17:969–974. doi: 10.1111/hpb.12468.
    1. Hasan S., Jacob R., Manne U., Paluri R. Advances in pancreatic cancer biomarkers. Oncol. Rev. 2019;13:410. doi: 10.4081/oncol.2019.410.
    1. Zhang Y., Yang J., Li H., Wu Y., Zhang H., Chen W. Tumor markers CA19-9, CA242 and CEA in the diagnosis of pancreatic cancer: A meta-analysis. Int. J. Clin. Exp. Med. 2015;8:11683.
    1. Yue T., Partyka K., Maupin K.A., Hurley M., Andrews P., Kaul K., Moser A.J., Zeh H., Brand R.E., Haab B.B. Identification of blood-protein carriers of the CA 19-9 antigen and characterization of prevalence in pancreatic diseases. Proteomics. 2011;11:3665–3674. doi: 10.1002/pmic.201000827.
    1. Wu E., Zhou S., Bhat K., Ma Q. CA 19-9 and pancreatic cancer. Clin. Adv. Hematol. Oncol. HO. 2013;11:53.
    1. Sayed M.M., Elshafie A.I., Lotfy M., Abdelhakam S.M., Rushdy M. Clinical significance of serum CA 19-9, CA 19-9/CRP ratio and CA19-9/total bilirubin ratio in differentiation between malignant and benign obstructive jaundice. Eur. Acad. Res. 2017;12:10271–10291.
    1. Greca G.L., Sofia M., Lombardo R., Latteri S., Ricotta A., Puleo S., Russello D. Adjusting CA19-9 values to predict malignancy in obstructive jaundice: Influence of bilirubin and C-reactive protein. World J. Gastroenterol. WJGJ. 2012;18:4150. doi: 10.3748/wjg.v18.i31.4150.
    1. Ghosh S., Baruah M., Yadav A.K., Das A.K. Role of CA 19-9 and its Ratio with CRP and Total Bilirubin in Differentiating Malignant from Benign Obstructive Jaundice. J. Clin. Diagn. Res. 2019;13:PC06–PC09. doi: 10.7860/JCDR/2019/38019.12477.
    1. Liu W., Liu Q., Wang W., Wang P., Chen J., Hong T., Zhang N., Li B., Qu Q., He X. Differential diagnostic roles of the serum CA19-9, total bilirubin (TBIL) and the ratio of CA19-9 to TBIL for benign and malignant. J. Cancer. 2018;9:1804. doi: 10.7150/jca.25093.
    1. Bismuth H., Majno P.E. Biliary strictures: Classification based on the principles of surgical treatment. World J. Surg. 2001;25:1241–1244. doi: 10.1007/s00268-001-0102-8.
    1. Blackbourne L.H., Earnhardt R.C., Sistrom C.L., Abbitt P., Jones R. The sensitivity and role of ultrasound in the evaluation of biliary obstruction. Am. Surg. 1994;60:683–690.
    1. Harvey R.T., Miller W.T., Jr. Acute biliary disease: Initial CT and follow-up US versus initial US and follow-up CT. Radiology. 1999;213:831–836. doi: 10.1148/radiology.213.3.r99dc17831.
    1. Feldman M.K., Coppa C.P. Noninvasive imaging of the biliary tree for the interventional radiologist. Tech. Vasc. Interv. Radiol. 2015;18:184–196. doi: 10.1053/j.tvir.2015.07.001.
    1. Baron R.L., Tublin M.E., Peterson M.S. Imaging the spectrum of biliary tract disease. Radiol. Clin. 2002;40:1325–1354. doi: 10.1016/S0033-8389(02)00045-3.
    1. Singh A., Gelrud A., Agarwal B. Biliary strictures: Diagnostic considerations and approach. Gastroenterol. Rep. 2015;3:22–31. doi: 10.1093/gastro/gou072.
    1. Rösch T., Meining A., Frühmorgen S., Zillinger C., Schusdziarra V., Hellerhoff K., Classen M., Helmberger H. A prospective comparison of the diagnostic accuracy of ERCP, MRCP, CT, and EUS in biliary strictures. Gastrointest. Endosc. 2002;55:870–876. doi: 10.1067/mge.2002.124206.
    1. Štoos-Veić T., Bilić B., Kaić G., Ostović K.T., Babić Ž., Kujundžić M. Biliary brush cytology for the diagnosis of malignancy: A single center experience. Coll. Antropol. 2010;34:139–143.
    1. Nakai Y., Isayamam H., Wang H.P., Rerknimitr R., Khor C., Yasuda I., Kogure H., Moon J.H., Lau J., Lakhtakia S. International consensus statements for endoscopic management of distal biliary stricture. J. Gastroenterol. Hepatol. 2019 doi: 10.1111/jgh.14955.
    1. Roth G.S., Bichard P., Fior-Gozlan M., Roth H., Auroux J., Risse O., Letoublon C., Laverrière M.H., Bricault I., Leroy V. Performance of bile aspiration plus brushing to diagnose malignant biliary strictures during endoscopic retrograde cholangiopancreatography. Endosc. Int. Open. 2016;4:E997–E1003. doi: 10.1055/s-0042-108854.
    1. Nakahara K., Michikawa Y., Morita R., Suetani K., Morita N., Sato J., Tsuji K., Ikeda H., Matsunaga K., Watanabe T. Diagnostic ability of endoscopic bile cytology using a newly designed biliary scraper for biliary strictures. Dig. Dis. Sci. 2019;64:241–248. doi: 10.1007/s10620-018-5217-y.
    1. Le N., Fillinger J., Szanyi S., Wichmann B., Nagy Z., Ivády G., Burai M., Tarpay Á., Pozsár J., Pap Á. Analysis of microRNA expression in brush cytology specimens improves the diagnosis of pancreatobiliary cancer. Pancreatology. 2019;19:873–879. doi: 10.1016/j.pan.2019.04.001.
    1. Jang S.I., Kwon N.H., Lim B.J., Nahm J.H., Park J.S., Kang C.M., Park S.R., Sd S.Y.L., Kang B.S., Kim S., et al. A new staining method using methionyl-tRNA synthetase 1 antibody for brushing cytology of bile duct cancer. Gastrointest. Endosc. 2019 doi: 10.1016/j.gie.2019.12.017.
    1. Kushnir V.M., Mullady D.K., Das K., Lang G., Hollander T.G., Murad F.M., Jackson S.A., Toney N.A., Finkelstein S.D., Edmundowicz S.A. The diagnostic yield of malignancy comparing cytology, FISH, and molecular analysis of cell free cytology brush supernatant in patients with biliary strictures undergoing endoscopic retrograde cholangiography (ERC): A prospective study. J. Clin. Gastroenterol. 2019;53:686. doi: 10.1097/MCG.0000000000001118.
    1. Korc P., Sherman S. ERCP tissue sampling. Gastrointest. Endosc. 2016;84:557–571. doi: 10.1016/j.gie.2016.04.039.
    1. Ayoub F., Yang D., Draganov P.V. Cholangioscopy in the digital era. Transl. Gastroenterol. Hepatol. 2018;3:82. doi: 10.21037/tgh.2018.10.08.
    1. Kulpatcharapong S., Pittayanon R., Kerr S.J., Rerknimitr R. Diagnostic performance of different cholangioscopes in patients with biliary strictures: A systematic review. Endoscopy. 2020;52:174–185. doi: 10.1055/a-1083-6105.
    1. Pérez-Cuadrado-Robles E., Deprez P.H. Indications for Single-Operator Cholangioscopy and Pancreatoscopy: An Expert Review. Curr. Treat. Options Gastroenterol. 2019;17:408–419. doi: 10.1007/s11938-019-00237-2.
    1. Sethi A., Doukides T., Sejpal D.V., Pleskow D.K., Slivka A., Adler D.G., Shah R.J., Edmundowicz S.A., Itoi T., Petersen B.T. Interobserver agreement for single operator choledochoscopy imaging: Can we do better? Diagn. Ther. Endosc. 2014;2014:1–4. doi: 10.1155/2014/730731.
    1. Sethi A., Tyberg A., Slivka A., Adler D.G., Desai A.P., Sejpal D.V., Pleskow D.K., Bertani H., Gan S.-I., Shah R. Digital Single-operator Cholangioscopy (DSOC) Improves Interobserver Agreement (IOA) and Accuracy for Evaluation of Indeterminate Biliary Strictures: The Monaco Classification. J. Clin. Gastroenterol. 2020 doi: 10.1097/MCG.0000000000001321.
    1. Nguyen N.Q., Schoeman M.N., Ruszkiewicz A. Clinical utility of EUS before cholangioscopy in the evaluation of difficult biliary strictures. Gastrointest. Endosc. 2013;78:868–874. doi: 10.1016/j.gie.2013.05.020.
    1. Sethi A., Chen Y.K., Austin G.L., Brown W.R., Brauer B.C., Fukami N.N., Khan A.H., Shah R.J. ERCP with cholangiopancreatoscopy may be associated with higher rates of complications than ERCP alone: A single-center experience. Gastrointest. Endosc. 2011;73:251–256. doi: 10.1016/j.gie.2010.08.058.
    1. Yeo S.J., Cho C.M., Jung M.K., Seo A.N., Bae H.I. Comparison of the Diagnostic Performances of Same-session Endoscopic Ultrasound-and Endoscopic Retrograde Cholangiopancreatography-guided Tissue Sampling for Suspected Biliary Strictures at Different Primary Tumor Sites. Korean J. Gastroenterol. 2019;73:213–218. doi: 10.4166/kjg.2019.73.4.213.
    1. Wang W., Shpaner A., Krishna S.G., Ross W.A., Bhutani M.S., Tamm E.P., Raju G.S., Xiao L., Wolff R.A., Fleming J.B. Use of EUS-FNA in diagnosing pancreatic neoplasm without a definitive mass on CT. Gastrointest. Endosc. 2013;78:73–80. doi: 10.1016/j.gie.2013.01.040.
    1. Xu M.M., Andalib I., Novikov A., Dawod E., Gabr M., Gaidhane M., Tyberg A., Kahaleh M. Endoscopic Therapy for Pancreatic Fluid Collections: A Definitive Management Using a Dedicated Algorithm. Clin. Endosc. 2019 doi: 10.5946/ce.2019.113.
    1. Yamaguchi M., Fukuda T., Nakahara M., Amano M., Takei D., Kawashima M., Sumi Y., Amano H., Yonehara S., Hanada K. Multicentric solid pseudopapillary neoplasms of the pancreas diagnosed by endoscopic ultrasound-guided fine needle aspiration: A case report. Surg. Case Rep. 2015;1:110. doi: 10.1186/s40792-015-0111-8.
    1. De Moura D.T.H., De Moura E.G.H., Bernardo W.M., De Moura E.T.H., Baracat F.I., Kondo A., Matuguma S.E., Artifon E.L.A. Endoscopic retrograde cholangiopancreatography versus endoscopic ultrasound for tissue diagnosis of malignant biliary stricture: Systematic review and meta-analysis. Endosc. Ultrasound. 2018;7:10. doi: 10.4103/2303-9027.193597.
    1. Ayres L.R., Kmiotek E.K., Lam E., Telford J.J. A comparison of endoscopic ultrasound-guided fine-needle aspiration and fine-needle biopsy in the diagnosis of solid pancreatic lesions. Can. J. Gastroenterol. Hepatol. 2018;2018:1–6. doi: 10.1155/2018/1415062.
    1. Van Riet P.A., Larghi A., Attili F., Rindi G., Nguyen N.Q., Ruszkiewicz A., Kitano M., Chikugo T., Aslanian H., Farrell J. A multicenter randomized trial comparing a 25-gauge EUS fine-needle aspiration device with a 20-gauge EUS fine-needle biopsy device. Gastrointest. Endosc. 2019;89:329–339. doi: 10.1016/j.gie.2018.10.026.
    1. Asokkumar R., Ka C.Y., Loh T., Ling L.K., San T.G., Ying H., Tan D., Khor C., Lim T., Soetikno R. Comparison of tissue and molecular yield between fine-needle biopsy (FNB) and fine-needle aspiration (FNA): A randomized study. Endosc. Int. Open. 2019;7:E955–E963. doi: 10.1055/a-0903-2565.
    1. Facciorusso A., Bajwa H.S., Menon K., Buccino V.R., Muscatiello N. Comparison between 22G aspiration and 22G biopsy needles for EUS-guided sampling of pancreatic lesions: A meta-analysis. Endosc Ultrasound. 2019:10. doi: 10.4103/eus.eus_4_19.
    1. Khan M.A., Grimm I.S., Ali B., Nollan R., Tombazzi C., Ismail M.K., Baron T.H. A meta-analysis of endoscopic ultrasound–fine-needle aspiration compared to endoscopic ultrasound–fine-needle biopsy: Diagnostic yield and the value of onsite cytopathological assessment. Endosc. Int. Open. 2017;5:E363–E375. doi: 10.1055/s-0043-101693.
    1. Valero V., III, Saunders T.J., He J., Weiss M.J., Cameron J.L., Dholakia A., Wild A.T., Shin E.J., Khashab M.A., O’Broin-Lennon A.M. Reliable detection of somatic mutations in fine needle aspirates of pancreatic cancer with next-generation sequencing: Implications for surgical management. Ann. Surg. 2016;263:153. doi: 10.1097/SLA.0000000000001156.
    1. Imaoka H., Sasaki M., Hashimoto Y., Watanabe K., Ikeda M. New Era of Endoscopic Ultrasound-Guided Tissue Acquisition: Next-Generation Sequencing by Endoscopic Ultrasound-Guided Sampling for Pancreatic Cancer. J. Clin. Med. 2019;8:1173. doi: 10.3390/jcm8081173.
    1. Sun B., Hu B. The role of intraductal ultrasonography in pancreatobiliary diseases. Endosc. Ultrasound. 2016;5:291.
    1. Heinzow H.S., Kammerer S., Rammes C., Wessling J., Domagk D., Meister T. Comparative analysis of ERCP, IDUS, EUS and CT in predicting malignant bile duct strictures. World J. Gastroenterol. WJGJ. 2014;20:10495. doi: 10.3748/wjg.v20.i30.10495.
    1. Krishna N.B., Saripalli S., Safdar R., Agarwal B. Intraductal US in evaluation of biliary strictures without a mass lesion on CT scan or magnetic resonance imaging: Significance of focal wall thickening and extrinsic compression at the stricture site. Gastrointest. Endosc. 2007;66:90–96. doi: 10.1016/j.gie.2006.10.020.
    1. Storm A.C., Lee L.S. Is Seeing Really Believing? Probe-based Confocal Laser Endomicroscopy in the Evaluation of Pancreaticobiliary Disease. J. Clin. Gastroenterol. 2016;50:359–365. doi: 10.1097/MCG.0000000000000505.
    1. Karia K., Kahaleh M. A review of probe-based confocal laser endomicroscopy for pancreaticobiliary disease. Clin. Endosc. 2016;49:462. doi: 10.5946/ce.2016.086.
    1. Almadi M.A., Neumann H. Probe based confocal laser endomicroscopy of the pancreatobiliary system. World J. Gastroenterol. 2015;21:12696. doi: 10.3748/wjg.v21.i44.12696.
    1. Fugazza A., Gaiani F., Carra M.C., Brunetti F., Lévy M., Sobhani I., Azoulay D., Catena F., de’Angelis G.L., de’Angelis N. Confocal laser endomicroscopy in gastrointestinal and pancreatobiliary diseases: A systematic review and meta-analysis. Biomed. Res. Int. 2016;2016:1–31. doi: 10.1155/2016/4638683.
    1. Tabibian J.H., Visrodia K.H., Levy M.J., Gostout C.J. Advanced endoscopic imaging of indeterminate biliary strictures. World J. Gastrointest. Endosc. 2015;7:1268. doi: 10.4253/wjge.v7.i18.1268.
    1. Shimada H., Endo I., Shimada K., Matsuyama R., Kobayashi N., Kubota K. The current diagnosis and treatment of benign biliary stricture. Surg. Today. 2012;42:1143–1153. doi: 10.1007/s00595-012-0333-3.
    1. Makary M.S., Farrell J.J., Khayat M., Chick J.F.B., Srinivasa R.N. Biliary Endoscopy for Benign and Malignant Biliary Strictures. Tech. Vasc. Interv. Radiol. 2019;22:135–138. doi: 10.1053/j.tvir.2019.04.005.
    1. Kim E.H., Kim H.-J., Oh H.-C., Lee K.H., Jung J.Y., Kim S., Lee S.S., Seo D.W., Kim M.-H., Lee S.K. The usefulness of percutaneous transhepatic cholangioscopy for identifying malignancies in distal commom bile duct strictures. J. Korean Med. Sci. 2008;23:579–585. doi: 10.3346/jkms.2008.23.4.579.
    1. Oliver J.B., Burnett A.S., Ahlawat S., Chokshi R.J. Cost-effectiveness of the evaluation of a suspicious biliary stricture. J. Surg. Res. 2015;195:52–60. doi: 10.1016/j.jss.2014.12.037.

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