Skip to main content
Log in

Role of Central Hypo-enhancement in the Hepatic Arterial Phase of Dynamic Computed Tomography in Patients with Mass-Forming Intrahepatic Cholangiocarcinoma

  • Original Scientific Report
  • Published:
World Journal of Surgery Aims and scope Submit manuscript

Abstract

Background/Purpose

The enhancement pattern in the hepatic arterial phase (HAP) of dynamic computed tomography (CT) is reportedly a prognostic marker in patients with intrahepatic cholangiocarcinoma (IHCC). This study was performed to clarify the significance of central hypo-enhancement in the HAP in patients with mass-forming IHCC.

Methods

Forty patients who had undergone initial surgical resection for mass-forming IHCC were enrolled. The dynamic CT was scanned 40 s after contrast agent injection as the HAP. A radiologist classified the patients into three groups based on the vascular pattern: the hyper-enhancement group (Hyper group), rim-enhancement group (Rim group), and hypo-enhancement group (Hypo group). The surgical specimens were immunohistochemically stained for hypoxia-inducible factor 1 (HIF-1). The correlation with clinicopathological findings and HIF-1 expression was investigated.

Results

The Hyper, Rim, and Hypo groups comprised 8, 7, and 25 patients, respectively. There were no significant correlations between the groups and clinicopathological factors. Overall survival (OS) was significantly worse in the Hypo than in the Hyper group (p = 0.03). OS was also significantly worse in the Rim + Hypo group (i.e., hypo-enhancement in the central tumor) than in the Hyper group (p = 0.04). Furthermore, inclusion in the Rim + Hypo group was a prognostic factor for OS (hazard ratio 6.68). High HIF-1 expression in the central part of the tumor was correlated with central hypo-enhancement (Hyper group: 25% and Rim + Hypo group: 72%).

Conclusions

Central hypo-enhancement was a prognostic factor in patients with IHCC. The high malignant potential of tumors with central hypo-enhancement might be associated with HIF-1 upregulation.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

IHCC:

Intrahepatic cholangiocarcinoma

HAP:

Hepatic arterial phase

CT:

Computed tomography

HIF-1:

Hypoxia-inducible factor 1

IHC:

Immunohistochemistry

ROI:

Region of interest

PI:

Periductal infiltrating

References

  1. Bridgewater J, Galle PR, Khan SA et al (2014) Guidelines for the diagnosis and management of intrahepatic cholangiocarcinoma. J Hepatol 60(6):1268–1289

    Article  Google Scholar 

  2. Zhang H, Yang T, Wu M et al (2016) Intrahepatic cholangiocarcinoma: Epidemiology, risk factors, diagnosis and surgical management. Cancer Lett 379(2):198–205

    Article  CAS  Google Scholar 

  3. Patel T (2002) Worldwide trends in mortality from biliary tract malignancies. BMC Cancer 3(2):10

    Article  Google Scholar 

  4. Roayaie S, Guarrena JV, Ye MQ et al (1998) Aggressive surgical treatment of intrahepatic cholangiocarcinoma: predictors of outcomes. J Am Coll Surg 187:365–372

    Article  CAS  Google Scholar 

  5. Isaji S, Kawarada Y, Taoka H et al (1999) Clinicopathological features and outcome of hepatic resection for intrahepatic cholangiocarcinoma in Japan. J Hepatobiliary Pancreat Surg 6:108–116

    Article  CAS  Google Scholar 

  6. Ariizumi S, Kotera Y, Takahashi Y et al (2011) Mass-forming intrahepatic cholangiocarcinoma with marked enhancement on arterial-phase computed tomography reflects favorable surgical outcomes. J Surg Oncol 104(2):130–139

    Article  Google Scholar 

  7. Yamamoto Y, Türkoğlu MA, Aramaki T et al (2016) Vascularity of intrahepatic cholangiocarcinoma on computed tomography is predictive of lymph node metastasis. Ann Surg Oncol 23(Suppl 4):485–493

    Article  Google Scholar 

  8. Kim SA, Lee JM, Lee KB et al (2011) Intrahepatic mass-forming cholangiocarcinomas: enhancement patterns at multiphasic CT, with special emphasis on arterial enhancement pattern–correlation with clinicopathologic findings. Radiology 260(1):148–157

    Article  Google Scholar 

  9. Nanashima A, Abo T, Murakami G et al (2013) Intrahepatic cholangiocarcinoma: relationship between tumor imaging enhancement by measuring attenuation and clinicopathologic characteristics. Abdom Imaging 38(4):785–792

    Article  Google Scholar 

  10. Fujita N, Asayama Y, Nishie A et al (2017) Mass-forming intrahepatic cholangiocarcinoma: enhancement patterns in the arterial phase of dynamic hepatic CT—correlation with clinicopathological findings. Eur Radiol 27(2):498–506

    Article  Google Scholar 

  11. Wang GL, Jiang BH, Rue EA et al (1995) Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci USA 92(12):5510–5514

    Article  CAS  Google Scholar 

  12. Iyer NV, Kotch LE, Agani F et al (1998) Cellular and developmental control of O2 homeostasis by hypoxia-inducible factor 1 alpha. Genes Dev 12(2):149–162

    Article  CAS  Google Scholar 

  13. Lee JW, Bae SH, Jeong JW et al (2004) Hypoxia-inducible factor (HIF-1)alpha: its protein stability and biological functions. Exp Mol Med 36(1):1–12

    Article  Google Scholar 

  14. Liver Cancer Study Group of Japan (2009) General rules for the clinical and pathological study of primary liver cancer. Kanehara & Co., Ltd, Tokyo

    Google Scholar 

  15. Morine Y, Shimada M, Ikegami T et al (2009) Usefulness of gemcitabine combined with 5-fluorouracil and cisplatin (GFP) in patients for unresectable biliary carcinoma. Hepatogastroenterology 56(90):307–312

    CAS  PubMed  Google Scholar 

  16. Teraoku H, Morine Y, Ikemoto T et al (2016) Role of thrombospondin-1 expression in colorectal liver metastasis and its molecular mechanism. J Hepatobiliary Pancreat Sci 23(9):565–573

    Article  Google Scholar 

  17. Zhao X, Gao S, Ren H et al (2014) Hypoxia-inducible factor-1 promotes pancreatic ductal adenocarcinoma invasion and metastasis by activating transcription of the actin-bundling protein fascin. Cancer Res 74(9):2455–2464

    Article  CAS  Google Scholar 

  18. Zhong H, De Marzo AM, Laughner E et al (1999) Overexpression of hypoxia-inducible factor 1 alpha in common human cancers and their metastases. Cancer Res 59(22):5830–5835

    CAS  PubMed  Google Scholar 

  19. Koike T, Kimura N, Miyazaki K et al (2004) Hypoxia induces adhesion molecules on cancer cells: a missing link between Warburg effect and induction of selectin-ligand carbohydrates. Proc Natl Acad Sci USA 101(21):8132–8137

    Article  CAS  Google Scholar 

  20. Giatromanolaki A, Koukourakis MI, Sivridis E et al (2001) Relation of hypoxia inducible factor 1α and 2α in operable non-small cell lung cancer to angiogenic/molecular profile of tumours and survival. Br J Cancer 85:881–890

    Article  CAS  Google Scholar 

  21. Sivridis E, Giatromanolaki A, Gatter KC et al (2002) Association of hypoxia-inducible factors 1αand 2αwith activated angiogenic pathways and prognosis in patients with endometrial carcinoma. Cancer 95:1055–1063

    Article  CAS  Google Scholar 

  22. Baba Y, Nosho K, Shima K et al (2010) HIF1A overexpression is associated with poor prognosis in a cohort of 731 colorectal cancers. Am J Pathol 176(5):2292–2301

    Article  CAS  Google Scholar 

  23. Lee J, Kim SH, Kang TW et al (2016) Mass-forming intrahepatic cholangiocarcinoma: diffusion-weighted imaging as a preoperative prognostic marker. Radiology 281(1):119–128

    Article  Google Scholar 

  24. Lewis S, Besa C, Wagner M et al (2018) Prediction of the histopathologic findings of intrahepatic cholangiocarcinoma: qualitative and quantitative assessment of diffusion-weighted imaging. Eur Radiol 28(5):2047–2057

    Article  Google Scholar 

Download references

Acknowledgement

We thank Angela Morben, DVM, ELS, from Edanz Group (www.edanzediting.com/ac), for editing a draft of this manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hiroki Teraoku.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Informed consent

This study was approved by the Research Ethics Committee of Tokushima University Hospital, and written informed consent was obtained from all patients.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Teraoku, H., Morine, Y., Uyama, N. et al. Role of Central Hypo-enhancement in the Hepatic Arterial Phase of Dynamic Computed Tomography in Patients with Mass-Forming Intrahepatic Cholangiocarcinoma. World J Surg 44, 2350–2358 (2020). https://doi.org/10.1007/s00268-020-05456-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00268-020-05456-8

Navigation