- Increased incidence? - Poor prognosis?

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1 Imaging of Cholangiocarcinoma Amir Reza Radmard, MD Assistant Professor Shariati hospital Tehran University of medical sciences

2 Definitions Tumors that arise from the bile duct epithelium. Accounts 10-20% of primary hepatic malignancies. Second most common primary liver tumor. Increasing importance: - Increased incidence? - Poor prognosis? Microscopy (WHO classification, 2010): - Most are adenocarcinoma - Highly infiltrative - Contains areas of fibrosis, necrosis and mucin mdppath.com

3 Traditional classification: Location AJCC/UICC 7 th edition Surgical treatment Intrahepatic (10%) - Mass forming Hepatic resection Perihilar (50%) - Periductal infiltrative - Biliary confluence Resection of bile ducts and ipsilateral liver Distal (40%) - Periductal infiltrative Whipple s operation or PPPD Juntermanns B, Ann Surg Oncol. 2013; 20: Mansour JC, HBP (Oxford). 2015; 17:

4 Traditional classification: Morphology Mass forming (20%) -3 yr DF survival, 29% -Mucosal spread Periductal infiltrative (>70%) -3 yr DF survival, 30% -Submucosal spread Intraductal growing (10%) - 3yr DF survival, 60% - Mucosal spread Lim JH, AJR. 2003; 181: Choi SB, Ann Surg Oncol. 2009;16: Cha JM, World J Gastroenterol. 2007;13:

5 Importance of classification of cholangiocarcinoma To understand biological behavior. Different mode of spread: - Longitudinal vs. vertical spread Different surgical technique. Different prognosis. - Intraductal growing >> Mass forming or periductal infiltrating Lim JH, AJR. 2003; 181:

6 Mode of spread: Periductal infiltrating vs. Intraductal growing Vertical extension Chung YE, Radiographics. 2009; 29: Usually defines resectability& curability Critical for prognosis PI: Submucosal, perivascular & perineural IDG: Submucosal

7 Recent classification based on cells of origin Canal of Hering: Lined by cholangiocytes and hepatocytes Association of intrahepatic CC and HCC with respect to the stem cells of origin Aishima et al. J Hepatobiliary Pancreat Sci. 2015; 22:

8 Recent classification based on cells of origin Large ducts 1-3 rd branch Peribiliary glands (+) Small ducts Interlobar/segmental ducts Peribiliary glands (-) Canals of Hering Hepatic progenitor cells The concepts of CCA and combined CC-HCC are evolving. Komuta M, et al. Hepatology. 2012;55:

9 1. Ultrasound: - > 3cm: Hyperechoic - < 3 cm: Hypo or isoechoic -Peripheral hypoechoic rim 2. CT scan Imaging of mass forming CCA Hypodense 3. MRI T1 low, T2 high 4. Peripheral arterial enhancement 5. Gradual centripetal enhancement Capsular retraction Satellite nodules Peripheral bile duct dilatation Vascular encasement Hepatolithiasis Cellular Fibrosis Chung YE, Radiographics. 2009; 29:

10 Imaging of mass forming CCA Madhusudhan KS, World J Radiol. 2015;28:28-44 Chung YE, Radiographics. 2009; 29:

11 Imaging of mass forming CCA

12 Imaging of mass forming CCA Target like diffusion restriction in 52 75% of mass-forming CCAs Seo N, AJR. 2017;209:W64-W75.

13 Imaging of mass forming CCA Lim J, Radiology. 2016;281: Poor prognosis Better prognosis Kim SA, Radiology. 2011;260: Prognostic role of preoperative DWI and on disease free survival and arterial enhancement

14 Imaging of Intraductal Growing CCA Ultrasound: - Localized or diffuse duct ectasia with or without an echogenic intraductal polypoid lesion. CT scan & MRI: 1- Diffuse and marked ductal dilatation with an intraductal mass that enhances at contrast-enhanced images. 2- Marked intrahepatic duct dilatation with no mass or stricture. 3- An intraductal polypoid mass within localized ductal dilatation. 4- An intraductal castlike lesion within a mildly dilated duct. Chung YE, Radiographics. 2009; 29:

15 Imaging of Intraductal Growing CCA Flat or fungating intraductal mass with proximal dilation. Mild arterial enhancement. No progressive enhancement in portal or delayed phase. Kim SY, ECR 2017.

16 Imaging of Intraductal Growing CCA Delgado Cordón F, Radiologia 2015;57:

17 Imaging of Intraductal Growing CCA Intraductal Papillary Neoplasm of the Bile ducts (IPNB) IPNB is a recognized precursor of invasive carcinoma. Share some histologic and clinical features with IPMNs of the pancreas. Dilated intrahepatic bile ducts filled with papillary or villous biliary neoplasm covering delicated fibrovascualr stalk. IPNB can progress to intraductal growing CCA. Ogawa H, Clin Radiol. 2012;67: Nakanuma Y, Best Pract Res Clin Gastroenterol 2015; 29: Rocha FG, HEPATOLOGY 2012;56:

18 Imaging of Intraductal Growing CCA Intraductal Papillary Neoplasm of the Bile ducts (IPNB) Dilatation of downstream bile duct consequent to mucin production is a characteristic feature. Intraductal linear or curvilinear hypointense striations (thread sign) in MRI highly specific for IPNB. Takanami K, Abdom Imaging 2011; 36: Hong GS, Eur Radiol 2016;26: Seo N, AJR. 2017;209:W64-W75.

19 Imaging of Periductal infiltrating CCA Ultrasound: Small, masslike lesion or diffuse bile duct thickening with or without obliteration of the bile duct CT scan & MRI: Diffuse periductal thickening with increased enhancement, abnormally dilated or irregularly narrowed duct Chung YE, Radiographics. 2009; 29:

20 Imaging of Periductal infiltrating CCA Kim SY, ECR 2017.

21 Imaging of Periductal infiltrating CCA Hilar periductal infiltrating CCA

22 Imaging of Periductal infiltrating CCA Hilar periductal infiltrating CCA

23 Imaging of Periductal infiltrating CCA Distal Periductal infiltrating CCA

24 Imaging of Periductal infiltrating CCA Biliary intraepithelial neoplasia (BilIN). Microscopic change in the biliary epithelium with abnormal epithelial cells, nuclear atypia and micropapillary projections. May be a precursor of periductal infiltrating CCA. Originates from peribiliary glands & chronic inflammation can induce it. Graded as BilIN-1 (low grade), BilIN-2 (intermediate grade), or BilIN-3 (high grade). Conventional imaging studies are limited for detection. Seo N, AJR. 2017;209:W64-W75. Sato Y, Int J Hepatol. 2014;2014:

25 Progression model of intrahepatic CCA Seo N, AJR. 2017;209:W64-W75.

26 1. Bismuth-Corlette classification. 2. AJCC Staging of CCA 3. Memorial Sloan-Kettering Cancer Center (MSKCC) classification Longitudinal : Bismuth-Corlette + Vertical or axial: AJCC MSKCC classification

27 Bismuth-Corlette classification. Staging of CCA Useful in determining type of surgery. Not indicative of resectability. Not indicative of survival.

28 Staging of CCA Lee JM, ESGAR 2014.

29 Staging of CCA Left hemihepatectomy, Pancreatoduodectomy and RT. H jejunostomy Lee JM, ESGAR 2014.

30 AJCC (7 th edition) Hilar cholangiocarcinoma Staging of CCA Little information about longitudinal extent of tumor. Less helpful for surgical planning.

31 Staging of CCA MSKCC classification T1 T2 The tumor involves the biliary confluence with unilateral involvement up to secondary biliary radicles. There is no portal vein involvement or liver atrophy. The tumor involves the biliary confluence with unilateral involvement up to secondary biliary radicles. There is ipsilateral portal vein involvement or ipsilateral hepatic lobar atrophy. T3 The tumor involves : 1) Biliary confluence with bilateral involvement up to secondary biliary radicles, 2) Unilateral extension to secondary biliary radicles with contralateral portal vein involvement. 3) Unilateral involvement up to secondary biliary radicles with contralateral hepatic lobar atrophy, or main/bilateral portal vein involvement.

32 Staging of CCA MSKCC classification

33 MSKCC classification Staging of CCA Correlates well with: Resectability Survival Dedicated preop. imaging and radiologist experience No consideration of hepatic artery invasion or lymph node metastasis. William R, Ann Surg Oct; 234:

34 Staging of CCA Proximal tumor extent PV invasion Lobar atrophy HA invasion LN or distant mets. Size of tumor Bismuth-Corrlete AJCC MSKCC New system by De-Oliveira ML, et al Comparison of various preoperative staging systems De-Oliveira ML, Hepatology. 2011; 53:

35 Criteria for unresectability of CCA Lee HY, Radiology. 2006;239:113-21

36 Criteria for unresectable hilar CCA Unresectable cases Bilateral segmental ductal extension. Unilateral atrophy with either contralateral segmental ductal or vascular inflow involvement Unilateral segmental ductal extension with contralateral vascular inflow involvement. Main portal vein or common hepatic artery involvement. Mansour JC, HPB (Oxford) 2015; 17:

37 Criteria for unresectable hilar CCA Unresectable due to tumor infiltration along the hepatoduodenal ligament Lee HY, Radiology. 2006;239:113-21

38 Perioperative staging of CCA A checklist for radiologist report Longitudinal and radial tumor spread Vascular involvement Lymph node involvement Distant metastases Liver volume Biliary, arterial and portal anomalies Other co-existing disease Jhaveri KS, J Magn Reson Imaging. 2015;42:

39 MDCT: Imaging modalities Relationship between important structures and evaluation of distant mets. Accurate for tumor location and vertical invasion Ductal spread is underestimated. Combined with CT angiography, CT venography or CT cholangiography. Hyodo T. Br J Radiol. 2012; 85: Akamatsu N. J Gastroenterol Hepatol. 2010;25:731-7

40 2D-thick slab Imaging modalities-mrcp 2D-Multi slice 3D MRCP T2W:HASTE/SSFSE TE> 600 msec Coronal oblique/ axial 4-6 cm thick Gross morphology T2W:HASTE/SSFSE TE< 180 msec Coronal/ axial 2-5 mm thick Periductal anatomy 3D T2W TE>600 msec Coronal 1-2 mm thick No gap Post processing

41 Imaging modalities Combination of MRCP & Contrast enhanced MRI for differentiating malignant from benign biliary strictures Kim JY, J Magn Reson Imaging. 2007;26: Yu XR, Clin Radiol. 2014;69: Li N, Clin Radiol. 2012;67:

42 MDCT < % Imaging modalities Accuracy in longitudinal spread of tumor CT + Direct cholangiography ~ 80% MRI ~ 71-80% Causes of inaccuracy: 1. Underestimation: Superficial spread of papillary tumor Sub epithelial spread of infiltrative type Anatomic variation 2. Overestimation: Cholangitis, drainage catheter, intra ductal necrotic material Seo N, Korean J Radiol. 2016; 17: Ruys AT, BR J Radiol; 2012:85;

43 Imaging modalities Accuracy of CT: Overestimation of tumor spread Overestimated by CT: Bismuth 4 Direct cholangiography: Bismuth 3a Lee JM, ESGAR 2014.

44 Imaging modalities Direct cholangiography can provide higher spatial resolution than CT or MRI Lee JM, ESGAR 2014.

45 Accurate staging and determination of resectability Longitudinal spread (ductal extension) Multimodality approach Multidisciplinary team Gastroenterologist Radiologist Surgeon Oncologist Pathologist Vertical spread High resolution imaging Extrahepatic disease CT, PET/CT or PET/MR

46 Take home message Incidence of CCA is increasing across the world. Concepts and classifications of CCA have been evolving. Longitudinal and vertical spread of CCA must be assessed by evaluation of key anatomic landmarks. MDCT with 3D reconstruction and MRCP combined with dynamic MRI play major role in staging but there is a tendency toward underestimation. Multimodality approach seems to be reasonable.

47 Thank you for your kind attention