Gastrolearning II modulo/8a lezione
Il colangiocarcinoma: Presentazione Clinica, Diagnosi e Trattamento
Prof. D. Alvaro - Università di Roma La Sapienza
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 !
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. 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. 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. 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. 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% !
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. *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. Open surgery 57% IH- vs 42% EH-CCA
Curative 45% IH- vs 29% EH-CCA
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. April 2010
*The efficacy of CisGem regimen confirmed (Furuse J. 2011)
* CisGem cost-effective vs Gem alone (Roth JA 2012)
BSG guidelines
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. 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. 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. 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