Il colangiocarcinoma: Presentazione Clinica, Diagnosi e Trattamento - Gastrolearning®

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Il colangiocarcinoma: Presentazione Clinica, Diagnosi e Trattamento
Prof. D. Alvaro - Università di Roma La Sapienza

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Il colangiocarcinoma: Presentazione Clinica, Diagnosi e Trattamento - Gastrolearning®

  1. 1. Univ. Sapienza, Rome, Italy.Domenico ALVARO, Univ.“Sapienza” Rome, Italy Neo Gr.E.Ca.S., Cosenza, 6 Dicembre 2013. IL COLANGIOCARCINOMA Presentazione Clinica, Diagnosi e Trattamento
  2. 2. Distal INTRAHEPATIC CHOLANGIOCARCINOMA (CCA): a heterogeneus cancer ! Hilar UICC classification WHO classification Klatskin t. second-order bile ducts
  3. 3. INTRAHEPATIC CCA (IH-CCA) Macroscopic pattern of growth ! Mass-forming Periductal- infiltrating Intraductal growing (LSCGJ) Mixed type (AJCC/UICC )
  4. 4. Mass-forming = 89 % Single mass = 67% HBV or HCV+ = 21% Cirrhosis = 10% Obstructive cholestasis = 10%
  5. 5. Anatomical location of IH-CCA 24/52 segment IV) IH-CCA, N= 116. Mass-forming = 94 % Single mass = 78.4% HBV or HCV+ = 30.2% Cirrhosis = 13.8% Obstructive cholestasis = 10% 50%
  6. 6. IH-CCA : PRESENTING SYMPTOMS (%) 4% Pruritus 4.4 % Other
  7. 7. IH-CCA: Algorithm for the diagnosis. Intrahepatic mass Esclude extrahepatic malignancy ! 4-phase MDCT, dynamic contrast-enhanced MRI contrast arterial enhancement and prompt venous washout HCC Cirrhosis > 1 cm The impact of imaging procedures in discriminating HCC vs mixed-CCA or combined HCC- CCA scarcely investigated !
  8. 8. N= 31 nodules, N 9 < 2 cm.
  9. 9. -Progressive homogeneous contrast uptake during the three vascular phase (42%) N. 40 IH-CCA nodules on cirrhosis (N= 11 < 2 cm): all nodules lacked the radiologic hallmark of HCC ! -Arterial periphereal-rim enhancement (50%);
  10. 10. N. 28 IH-CCA nodules on cirrhosis: < 3 cm: 5/8 washout pattern similar to HCC ! > 3 cm: 20/20 no washout, 9/20 arterial periphereal-rim enhanc.!
  11. 11. Biopsy IH-CCA: Algorithm for the diagnosis. Intrahepatic mass Esclude extrahepatic malignancy ! 4-phase MDCT, dynamic contrast-enhanced MRI contrast arterial enhancement and prompt venous washout HCC Atypical appearance cirrhosisnon-cirrhotic liver
  12. 12. No marker specific for CCA! Immunohistochemistry (IHC) marker panel CK7 (+), CK20(-/+), CDX-2(-), TTF-1 (-), PR (-), BRST-2 (-) , PSA (-) Histology/IHC cannot differentiate CCA from metastatic gallbladder cancer, pancreas, or upper gastrointestinal tract Histological diagnosis of IH-CCA: a diagnosis of exclusion ! (HCC ?, metastasis ? ) MembranousN-cadherin +: sensitivity 67%; specificity 88% Membranous N-cadherin +/CK7+:sensitivity 67% ; specificity 98% Sempoux C. et al. Seminar in liver disease Vol. 31, 2011. .
  13. 13. CHOLANGIOCARCINOMA: Diagnosis Novel target genes and a valid biomarker panel identified for CCA. Andresen K. et al. Epigenetics 2012; 7 (11). CDO1, DCLK1, SFRP1 and ZSCAN18, high methylation frequencies in CCA ….unmethylated in controls. At least one of these four biomarkers was positive in 87% of the tumor samples, with a specificity of 100% !
  14. 14. Nodular Nodular Periductal- infiltrating Intraductal growing (LSCGJ) Exophyti c EXTRAHEPATIC CCA (EH-CCA) Classification based on Macroscopic pattern of growth !
  15. 15. Nodular+PI = 94% Obstructive jaundice = 79 % (299/376) Biliary drainage = 74.3% BSG guidelines
  16. 16. EH-CCA, N= 102 Nodular-PI = 82 % HBV or HCV+ = 18.6 % Cirrhosis = 4.3% Obstructive cholestasis = 70%
  17. 17. EH-CCA : PRESENTING SYMPTOMS (%) 6.8% Pruritus 3,9 % abdominal pain 5.9 % No symptoms 9.9 % others
  18. 18. ObservationCCA EH-CCA: Algorithm for the diagnosis Suspicion of CCA (Clinical + US) MRI+MRCP ERCP (citology, brushing, FISH, biopsy) Under evaluation: Endoscopic Ultrasound (EUS), Intraductal Ultrasound (IDUS), Choledochoscopy, cholangioscopy (chromoendoscopy, confocal endoscopy, narrow band imaging) Neg. citology, brushing, FISH No dominant stricture CCA Biopsy (tumor spread !!) Positive biopsy, citology, brushing or polysomy(Fish) Vascular enhancement Mass-like appearance Biliary stricture Dominant stricture in PSC PET (?) Hot spot? yes NO Definite diagnosis Perihilar mass with associated biliary stricture + hypertrophy– atrophy complex + vascular encasement microscopic confirmation is needed to confirm the diagnosis Presence and level of stricture sensitivity, specificity = 98% Malignancy detection sensitivity 88%, specificity = 95% (Ann. Int. Med 2003)
  19. 19. CHOLANGIOCARCINOMA Diagnosis (Gut 2012)
  20. 20. CHOLANGIOCARCINOMA Diagnosis (Gut 2012)
  21. 21. CHOLANGIOCARCINOMA Diagnosis
  22. 22. CHOLANGIOCARCINOMA Diagnosis
  23. 23. Definitive diagnosis before surgery: 61% No evidence of cancer on resected tissues 10 % *Polisomy on bile citology or brushing *IGF1 on bile samples (ERCP) Never reached routine clinical use !
  24. 24. *Surgery is the only curative treatment for CCA ! 5-year survival rates: IH-CCA 22-44 % distal EH-CCA 27-37 % hilar EH-CCA 11-41 % *Survival depends: R0 or R1 status, vascular invasion and lymphonode metastases. CHOLANGIOCARCINOMA TREATMENT !
  25. 25. Open surgery 57% IH- vs 42% EH-CCA Curative 45% IH- vs 29% EH-CCA
  26. 26. CHOLANGIOCARCINOMA Adjuvant therapy ? * No evidence support postoperative adjuvant therapy ! *A phase III RCT with Mito+5FU…. no advantage (only GBC) * UK NCRI-BILCAP study with CAPECITABINE is ongoing (final report 2014) *France-NCT: GEMOX (final report 2015) BSG guidelines
  27. 27. April 2010 *The efficacy of CisGem regimen confirmed (Furuse J. 2011) * CisGem cost-effective vs Gem alone (Roth JA 2012) BSG guidelines
  28. 28. Metanalysis of Survival, Complications, and Imaging Response following Chemotherapy-based Transarterial Therapy in Patients with Unresectable Intrahepatic Cholangiocarcinoma. Ray CE, J Vasc Int. Radiol. 2013 MESSAGE: transarterial chemotherapy-based treatments for CCA appears to confer a survival benefit of 2-7 months compared with systemic therapies !
  29. 29. Yttrium-90 Radioembolization for IH-CCA . Mouli S. et al. J Vasc Int. Radiol. 2013 46 pts IH-CCA unresectable. 25% partial response 73% stable disease 5 pts converted to resectable status !
  30. 30. A phase II trial of sorafenib (SOR) in patients (pts) with advanced cholangiocarcinoma (CCA). C. Dealis ASCO 2008. CONCLUSIONS: Sorafenib as a single agent has a low activity in cholangiocarcinoma !
  31. 31. Targeted agents in development for CCA Cholangiocarcinoma: registered trials Sorafenib + Gem.+ cisplatin phase II Cediranib + Folfox phase II Panitumumab + Gem.+ Irinotecan phase II Vandenatinib + Gem. phase II Sunitinib phase II Pazopanib + GSK1120212 phase II Erlotinib phase II

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