Il colangiocarcinoma: Presentazione Clinica, Diagnosi e Trattamento - Gastrolearning®
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Transcript of Il colangiocarcinoma: Presentazione Clinica, Diagnosi e Trattamento - Gastrolearning®
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
Distal
INTRAHEPATIC
CHOLANGIOCARCINOMA (CCA): a heterogeneus cancer !
Hilar
UICC classification
WHO classification
Klatskin t.second-order bile ducts
INTRAHEPATIC CCA (IH-CCA)Macroscopic pattern of growth !
Mass-formingPeriductal-infiltrating
Intraductal growing (LSCGJ)
Mixed type (AJCC/UICC )
Mass-forming = 89 %Single mass = 67%HBV or HCV+ = 21%Cirrhosis = 10%Obstructive cholestasis = 10%
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%
IH-CCA : PRESENTING SYMPTOMS (%)
4% Pruritus
4.4 % Other
IH-CCA: Algorithm for the diagnosis. Intrahepatic
massEsclude
extrahepatic malignancy !
4-phase MDCT, dynamic contrast-
enhanced MRI contrast arterial enhancement and
prompt venous washout
HCC
Cirrhosis
> 1 cmThe impact of imaging procedures in
discriminating HCC vs mixed-CCA or combined HCC-CCA
scarcely investigated !
N= 31 nodules, N 9 < 2 cm.
-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%);
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.!
Biopsy
IH-CCA: Algorithm for the diagnosis. Intrahepatic
massEsclude
extrahepatic malignancy !
4-phase MDCT, dynamic contrast-
enhanced MRI contrast arterial enhancement and
prompt venous washout
HCC
Atypical appeara
nce
cirrhosisnon-cirrhotic
liver
No marker specific for CCA!
Immunohistochemistry (IHC) marker panel CK7 (+), CK20(-/+), CDX-2(-),
TTF-1 (-), PR (-), BRST-2 (-) , PSA (-)
Histology/IHC cannot differentiateCCA 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. .
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% !
Nodular
Nodular
Periductal-infiltrating
Intraductal growing
(LSCGJ)Exophytic
EXTRAHEPATIC CCA (EH-CCA) Classification based on Macroscopic pattern of
growth !
Nodular+PI = 94% Obstructive jaundice = 79 % (299/376)Biliary drainage = 74.3%
BSG guidelines
EH-CCA, N= 102
Nodular-PI = 82 %HBV or HCV+ = 18.6 %Cirrhosis = 4.3%Obstructive cholestasis = 70%
EH-CCA : PRESENTING SYMPTOMS (%)
6.8% Pruritus
3,9 % abdominal pain
5.9 % No symptoms
9.9 % others
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)
CHOLANGIOCARCINOMADiagnosis
(Gut 2012)
CHOLANGIOCARCINOMADiagnosis
(Gut 2012)
CHOLANGIOCARCINOMADiagnosis
CHOLANGIOCARCINOMADiagnosis
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 !
*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.
CHOLANGIOCARCINOMATREATMENT !
Open surgery 57% IH- vs 42% EH-CCA
Curative 45% IH- vs 29% EH-CCA
CHOLANGIOCARCINOMAAdjuvant 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
April 2010
*The efficacy of CisGem regimen confirmed (Furuse J. 2011)
* CisGem cost-effective vs Gem alone (Roth JA 2012)
BSG guidelines
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 !
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 !
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 !
Targeted agents in development for CCA
Cholangiocarcinoma: registered trials
Sorafenib + Gem.+ cisplatin phase IICediranib + Folfox phase IIPanitumumab + Gem.+ Irinotecan phase IIVandenatinib + Gem. phase IISunitinib phase IIPazopanib + GSK1120212 phase IIErlotinib phase II