Skip to main content
SpringerLink
Log in

Differences on metabolic behavior between intra and extrahepatic cholangiocarcinomas at 18F-FDG–PET/CT: prognostic implication of metabolic parameters and tumor markers

  • Research Article
  • Published:
Clinical and Translational Oncology Aims and scope Submit manuscript

Abstract

Background and purpose

Cholangiocarcinoma is an infrequent neoplasm barely studied with 18F-FDG–PET/CT. We evaluated the metabolic behavior of cholangiocarcinoma in PET/CT according to its location (intra or extrahepatic) and analyzed the relationship between metabolic parameters of the primary tumor and tumor markers (CA19-9 and CEA), determining their prognostic significance.

Methods

Retrospective study of PET/CT of 60 patients with untreated cholangiocarcinoma, divided into two groups according to tumor location. FDG uptake was evaluated visually and semiquantitatively [SUVmax and tumor-to-liver ratio (TLR)], and differences between intra and extrahepatic cholangiocarcinomas were tested, both for FDG uptake in the primary tumor and for the presence of regional or distant disease (per-patient), as well as regarding tumor marker levels. A correlation between metabolic parameters and tumor markers was performed, and prognostic value of these factors was determined (univariate and multivariate analyses).

Results

Intrahepatic cholangiocarcinomas were significantly more FDG-avid than extrahepatic ones (p = 0.006 for SUVmax; p = 0.002 for TLR). There were differences neither between both groups considering the capacity of PET/CT to detect regional (p = 0.261) and distant involvement (p = 0.876), nor regarding the levels of tumor markers (p = 0.160 for CA19-9; p = 0.708 for CEA). Metabolic parameters and tumor markers showed a weak positive correlation (R2 0.22–0.27). At the multivariate analysis, advanced stage (p = 0.024), increased CEA (p = 0.022), and higher TLR (p = 0.003) were significantly related with shorter overall survival.

Conclusions

Intra and extrahepatic cholangiocarcinomas behave differently on PET/CT, though no differences between both groups exist in its capacity to detect regional or distant disease. Metabolic parameters and levels of tumor markers seem to relate with tumor burden, impacting in prognosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Khan SA, Toledano MB, Taylor-Robinson SD. Epidemiology, risk factors, and pathogenesis of cholangiocarcinoma. HPB (Oxf). 2008;10:77–82.

    Article  CAS  Google Scholar 

  2. Charbel H, Al-Kawas FH. Cholangiocarcinoma: epidemiology, risk factors, pathogenesis, and diagnosis. Curr Gastroenterol Rep. 2011;13:182–7.

    Article  PubMed  Google Scholar 

  3. Razumilava N, Gores GJ. Cholangiocarcinoma. Lancet. 2014;383:2168–79.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Altekruse SF, Petrick JL, Rolin AI, Cuccinelli JE, Zou Z, Tatalovich Z, McGlynn KA. Geographic variation of intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and hepatocellular carcinoma in the United States. PLoS One. 2015;10:e0120574.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Palmer WC, Patel T. Are common factors involved in the pathogenesis of primary liver cancers? A meta-analysis of risk factors for intrahepatic cholangiocarcinoma. J Hepatol. 2012;57:69–76.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Edge SB, Compton CC. The American joint committee on cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010;17:1471–4.

    Article  PubMed  Google Scholar 

  7. Horgan AM, Amir E, Walter T, Knox JJ. Adjuvant therapy in the treatment of biliary tract cancer: a systematic review and meta-analysis. J Clin Oncol. 2012;30:1934–40.

    Article  PubMed  Google Scholar 

  8. Petrowsky H, Wildbrett P, Husarik DB, Hany TF, Tam S, Jochum W, Clavien PA. Impact of integrated positron emission tomography and computed tomography on staging and management of gallbladder cancer and cholangiocarcinoma. J Hepatol. 2006;45:43–50.

    Article  PubMed  Google Scholar 

  9. Corvera CU, Blumgart LH, Akhurst T, DeMatteo RP, D’Angelica M, Fong Y, Jarnagin WR. 18F-fluorodeoxyglucose positron emission tomography influences management decisions in patients with biliary cancer. J Am Coll Surg. 2008;206:57–65.

    Article  PubMed  Google Scholar 

  10. Khan SA, Davidson BR, Goldin R, Heaton N, Karani J, Pereira SP, Rosenberg WM, Tait P, Taylor-Robinson SD, Thillainayagam AV, Thomas HC, Wasan H. British society of gastroenterology. Guidelines for the diagnosis and treatment of cholangiocarcinoma: an update. Gut. 2012;61:1657–69.

    Article  CAS  PubMed  Google Scholar 

  11. Gores GJ. Early detection and treatment of cholangiocarcinoma. Liver Transpl. 2000;6:S30–4.

    Article  CAS  PubMed  Google Scholar 

  12. Patel AH, Harnois DM, Klee GG, LaRusso NF, Gores GJ. The utility of CA 19-9 in the diagnoses of cholangiocarcinoma in patients without primary sclerosing cholangitis. Am J Gastroenterol. 2000;95:204–7.

    Article  CAS  PubMed  Google Scholar 

  13. Annunziata S, Caldarella C, Pizzuto DA, Galiandro F, Sadeghi R, Giovanella L, Treglia G. Diagnostic accuracy of fluorine-18-fluorodeoxyglucose positron emission tomography in the evaluation of the primary tumor in patients with cholangiocarcinoma: a meta-analysis. Biomed Res Int. 2014;2014:247693.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Albazaz R, Patel CN, Chowdhury FU, Scarsbrook AF. Clinical impact of FDG PET–CT on management decisions for patients with primary biliary tumours. Insights Imaging. 2013;4:691–700.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Oliveira IS, Kilcoyne A, Everett JM, Mino-Kenudson M, Harisinghani MG, Ganesan K. Cholangiocarcinoma: classification, diagnosis, staging, imaging features, and management. Abdom Radiol (NY). 2017;42:1637–49.

    Article  Google Scholar 

  16. Arellano RS, Sahani DV. Imaging of Cholangiocarcinoma. Dig Dis Interv. 2017;1:8–13.

    Article  Google Scholar 

  17. Kim JY, Kim MH, Lee TY, Hwang CY, Kim JS, Yun SC, Lee SS, Seo DW, Lee SK. Clinical role of 18F-FDG PET–CT in suspected and potentially operable cholangiocarcinoma: a prospective study compared with conventional imaging. Am J Gastroenterol. 2008;103:1145–51.

    Article  PubMed  Google Scholar 

  18. Choi EK, Yoo IR, Kim SH, O JH, Choi WH, Na SJ, Park SY. The clinical value of dual-time point 18F-FDG PET/CT for differentiating extrahepatic cholangiocarcinoma from benign disease. Clin Nucl Med. 2013;38:e106–11.

    Article  PubMed  Google Scholar 

  19. Park TG, Yu YD, Park BJ, Cheon GJ, Oh SY, Kim DS, Choe JG. Implication of lymph node metastasis detected on 18F-FDG PET/CT for surgical planning in patients with peripheral intrahepatic cholangiocarcinoma. Clin Nucl Med. 2014;39:1–7.

    Article  PubMed  Google Scholar 

  20. Jiang L, Tan H, Panje CM, Yu H, Xiu Y, Shi H. Role of 18F-FDG PET/CT Imaging in Intrahepatic cholangiocarcinoma. Clin Nucl Med. 2016;41:1–7.

    Article  PubMed  Google Scholar 

  21. Wei M, Lü L, Lin P, Chen Z, Quan Z, Tang Z. Multiple cellular origins and molecular evolution of intrahepatic cholangiocarcinoma. Cancer Lett. 2016;379:253–61.

    Article  CAS  PubMed  Google Scholar 

  22. Sekiya S, Suzuki A. Intrahepatic cholangiocarcinoma can arise from Notch-mediated conversion of hepatocytes. J Clin Invest. 2012;122:3914–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Cardinale V, Carpino G, Reid L, Gaudio E, Alvaro D. Multiple cells of origin in cholangiocarcinoma underlie biological, epidemiological and clinical heterogeneity. World J Gastrointest Oncol. 2012;4:94–102.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Sakamoto Y, Kokudo N, Matsuyama Y, Sakamoto M, Izumi N, Kadoya M, Kaneko S, Ku Y, Kudo M, Takayama T, Nakashima O. Liver Cancer study group of Japan. Proposal of a new staging system for intrahepatic cholangiocarcinoma: analysis of surgical patients from a nationwide survey of the liver cancer study group of Japan. Cancer. 2016;122:61–70.

    Article  PubMed  Google Scholar 

  25. Anderson CD, Rice MH, Pinson CW, Chapman WC, Chari RS, Delbeke D. Fluorodeoxyglucose PET imaging in the evaluation of gallbladder carcinoma and cholangiocarcinoma. J Gastrointest Surg. 2004;8:90–7.

    Article  PubMed  Google Scholar 

  26. Moon CM, Bang S, Chung JB, Park SW, Song SY, Yun M, Lee JD. Usefulness of 18F-fluorodeoxyglucose positron emission tomography in differential diagnosis and staging of cholangiocarcinomas. J Gastroenterol Hepatol. 2008;23:759–65.

    Article  PubMed  Google Scholar 

  27. Suzuki H, Komuta M, Bolog A, Yokobori T, Wada S, Araki K, Kubo N, Watanabe A, Tsukagoshi M, Kuwano H. Relationship between 18-F-fluoro-deoxy-d-glucose uptake and expression of glucose transporter 1 and pyruvate kinase M2 in intrahepatic cholangiocarcinoma. Dig Liver Dis. 2015;47:590–6.

    Article  CAS  PubMed  Google Scholar 

  28. Hyder O, Hatzaras I, Sotiropoulos GC, Paul A, Alexandrescu S, Marques H, Pulitano C, Barroso E, Clary BM, Aldrighetti L, Ferrone CR, Zhu AX, Bauer TW, Walters DM, Groeschl R, Gamblin TC, Marsh JW, Nguyen KT, Turley R, Popescu I, Hubert C, Meyer S, Choti MA, Gigot JF, Mentha G, Pawlik TM. Recurrence after operative management of intrahepatic cholangiocarcinoma. Surgery. 2013;153:811–8.

    Article  PubMed  Google Scholar 

  29. Lee Y, Yoo IR, Boo SH, Kim H, Park HL, Hyun OJ. The role of F-18-FDG PET/CT in intrahepatic cholangiocarcinoma. Nucl Med Mol Imaging. 2017;51:69–78.

    Article  CAS  PubMed  Google Scholar 

  30. Lee JY, Kim HJ, Yim SH, Shin DS, Yu JH, Ju DY, Park JH, Park DI, Cho YK, Sohn CI, Jeon WK, Kim BI. Primary tumor maximum standardized uptake value measured on 18F-fluorodeoxyglucose positron emission tomography-computed tomography is a prognostic value for survival in bile duct and gallbladder cancer. Korean J Gastroenterol. 2013;62:227–33.

    Article  PubMed  Google Scholar 

  31. Song JY, Lee YN, Kim YS, Kim SG, Jin SJ, Park JM, Choi GS, Chung JC, Lee MH, Cho YH, Choi MH, Kim DC, Choi HJ, Moon JH, Lee SH, Jeong SW, Jang JY, Kim HS, Kim BS. Predictability of preoperative 18F-FDG PET for histopathological differentiation and early recurrence of primary malignant intrahepatic tumors. Nucl Med Commun. 2015;36:319–27.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Nuclear Medicine, PET Unit-IDI, Hospital Universitari de Bellvitge-IDIBELL, C/Feixa Llarga s/n, L’Hospitalet de Llobregat, 08907, Barcelona, Spain

    A. Sabaté-Llobera, L. Gràcia-Sánchez, G. Reynés-Llompart, J. Robles, J. Mestres-Martí & C. Gámez-Cenzano

  2. Department of Medical Physics, Institut Català d’Oncologia-Hospital Duran i Reynals, Av. Granvia 199-203, L’Hospitalet de Llobregat, 08908, Barcelona, Spain

    G. Reynés-Llompart

  3. Department of Surgery, Hospital Universitari de Bellvitge-IDIBELL, C/Feixa Llarga s/n, L’Hospitalet de Llobregat, 08907, Barcelona, Spain

    E. Ramos & L. Lladó

  4. Department of Pathology, Hospital Universitari de Bellvitge-IDIBELL, C/Feixa Llarga s/n, L’Hospitalet de Llobregat, 08907, Barcelona, Spain

    T. Serrano

Authors
  1. A. Sabaté-Llobera
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L. Gràcia-Sánchez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G. Reynés-Llompart
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E. Ramos
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. L. Lladó
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. J. Robles
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. T. Serrano
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. J. Mestres-Martí
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. C. Gámez-Cenzano
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. Sabaté-Llobera.

Ethics declarations

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

This is a retrospective work involving human participants. The final manuscript was revised and approved by the Ethics Committee of our institution.

Informed consent

Informed consent was waived due to its retrospective nature, though prior to data analysis, all patients were de-identified, and confidential information was protected according to national standards.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sabaté-Llobera, A., Gràcia-Sánchez, L., Reynés-Llompart, G. et al. Differences on metabolic behavior between intra and extrahepatic cholangiocarcinomas at 18F-FDG–PET/CT: prognostic implication of metabolic parameters and tumor markers. Clin Transl Oncol 21, 324–333 (2019). https://doi.org/10.1007/s12094-018-1926-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12094-018-1926-0

Keywords

Search

Navigation