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Review
. 2008 Jul;48(1):308-21.
doi: 10.1002/hep.22310.

Cholangiocarcinoma: advances in pathogenesis, diagnosis, and treatment

Boris Blechacz  1 , Gregory J Gores
Affiliations
Review

Cholangiocarcinoma: advances in pathogenesis, diagnosis, and treatment

Boris Blechacz et al. Hepatology. 2008 Jul.
No abstract available

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Conflict of interest statement

Potential conflict of interest: Nothing to report.

Figures

Fig. 1
Fig. 1
IL-6 signaling and therapeutic targets in CCA. A schematic overview of IL-6 signaling and its downstream effectors as well as examples of potential therapeutic interventions is depicted. IL-6 binds to its receptor, which consists of the common receptor unit gp130 and the IL-6–specific subunit gp80. Activation of this receptor complex results in downstream activation of the JAK/STAT, PI3K/Akt, and MAPK signaling pathways. Activation of the JAK/STAT pathway results in nuclear translocation of phosphorylated STAT3 and transcriptional up-regulation of target genes, including the antiapoptotic Mcl-1. In addition, IL-6 increases EGFR expression by decreasing its promoter methylation. Activation of phosphoinositide 3-kinase (PI3K) results in phosphorylation and activation of Akt kinase, which in turn inhibits proapoptotic factors and facilitates cell growth. Activation of p38 MAPK decreases negative cell cycle regulators and is critical for CCA proliferation. Inhibitors of IL-6 receptor, Akt, MAPK, or JAK signaling, as well as bcl-2 protein inhibitors, have the potential of inhibiting these pathways.
Fig. 2
Fig. 2
Imaging of CCA. A gadolinium-enhanced MRI scan of the liver with ferumoxide of a patient with hilar CCA is depicted. The arrow inserted into the T2-weighted MRI scan points out the biliary tumor.
Fig. 3
Fig. 3
Diagnostic evaluation of hilar CCA. In patients with clinical suspicion of hilar CCA, CA 19-9 serum analysis, endoscopic retrograde cholangiopancreatography, and conventional as well as molecular cytologic analysis of endoscopically obtained biliary brushings of suspicious areas should be performed. In cases where these tests are negative, observation is recommended. In cases in which a dominant stricture is identified, Ca 19-9 serum levels are >129 U/mL, biopsy/cytology are positive for carcinoma and/or polysomy is shown, management for CCA should be initiated. In indeterminate cases, gadolinium-enhanced MRI of the liver with ferumoxide should be performed. If a mass lesion and/or vascular encasement are identified, management of CCA should be initiated. If the MRI scan is negative but there is significant concern for CCA, PET can be performed. If “hot spots” are identified, further management should be directed toward CCA. If the PET scan is negative, careful observation is recommended. In cases with a negative MRI scan and minimal concern for CCA, patients can be observed.
See this image and copyright information in PMC

References

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