Skip to main content
SpringerLink
Log in

A multi-parameter intrahepatic cholangiocarcinoma scoring system based on modified contrast-enhanced ultrasound LI-RADS M criteria for differentiating intrahepatic cholangiocarcinoma from hepatocellular carcinoma

  • Hepatobiliary
  • Published:
Abdominal Radiology Aims and scope Submit manuscript

Abstract

Purpose

To develop a multi-parameter intrahepatic cholangiocarcinoma (ICC) scoring system and compare its diagnostic performance with contrast-enhanced ultrasound (CEUS) liver imaging reporting and data system M (LR-M) criteria for differentiating ICC from hepatocellular carcinoma (HCC).

Methods

This retrospective study enrolled 62 high-risk patients with ICCs and 62 high-risk patients with matched HCCs between January 2022 and December 2022 from two institutions. The CEUS LR-M criteria was modified by adjusting the early wash-out onset (within 45 s) and the marked wash-out (within 3 min). Then, a multi-parameter ICC scoring system was established based on clinical features, B-mode ultrasound features, and modified LR-M criteria.

Result

We found that elevated CA 19-9 (OR=12.647), lesion boundary (OR=11.601), peripheral rim-like arterial phase hyperenhancement (OR=23.654), early wash-out onset (OR=7.211), and marked wash-out (OR=19.605) were positive predictors of ICC, whereas elevated alpha-fetoprotein (OR=0.078) was a negative predictor. Based on these findings, an ICC scoring system was established. Compared with the modified LR-M and LR-M criteria, the ICC scoring system showed the highest area under the curve (0.911 vs. 0.831 and 0.750, both p<0.05) and specificity (0.935 vs. 0.774 and 0.565, both p<0.05). Moreover, the numbers of HCCs categorized as LR-M decreased from 27 (43.5%) to 14 (22.6%) and 4 (6.5%) using the modified LR-M criteria and ICC scoring system, respectively.

Conclusion

The modified LR-M criteria-based multi-parameter ICC scoring system had the highest specificity for diagnosing ICC and reduced the number of HCC cases diagnosed as LR-M category.

Graphical abstract

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
Fig. 5
Fig. 6

Similar content being viewed by others

Abbreviations

ICC:

Intrahepatic cholangiocarcinoma

HCC:

Hepatocellular carcinoma

CEUS:

Contrast-enhanced ultrasound

BUS:

B-mode ultrasound

LI-RADS:

Liver imaging reporting and data system

APHE:

Arterial phase hyperenhancement

AP:

Arterial phase

PVP:

Portal venous phase

LP:

Late phase

rim APHE:

Rim-like hyperenhancement

IRQ:

Interquartile range

ROC:

Receiver operating characteristic

HBV:

Hepatitis B virus

HCV:

Hepatitis C virus

AFP:

Alpha-fetoprotein

OR:

Odds ratio

CI:

Confidence interval

AUC:

Area under the curve

References

  1. Valle JW, Kelley RK, Nervi B, Oh DY, Zhu AX. (2021) Biliary tract cancer. Lancet, 397(10272):428-444. https://doi.org/10.1016/S0140-6736(21)00153-7

    Article  CAS  PubMed  Google Scholar 

  2. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 68(6):394-424. https://doi.org/10.3322/caac.21492

    Article  PubMed  Google Scholar 

  3. Bridgewater J, Galle PR, Khan SA, Llovet JM, Park JW, Patel T, Pawlik TM, Gores GJ. (2014) Guidelines for the diagnosis and management of intrahepatic cholangiocarcinoma. J Hepatol, 60(6):1268-1289. https://doi.org/10.1016/j.jhep.2014.01.021

    Article  PubMed  Google Scholar 

  4. Xue TC, Zhang BH, Ye SL, Ren ZG. (2015) Differentially expressed gene profiles of intrahepatic cholangiocarcinoma, hepatocellular carcinoma, and combined hepatocellular-cholangiocarcinoma by integrated microarray analysis. Tumour Biol, 36(8):5891-5899. https://doi.org/10.1007/s13277-015-3261-1

    Article  CAS  PubMed  Google Scholar 

  5. Mavros MN, Economopoulos KP, Alexiou VG, Pawlik TM. (2014) Treatment and prognosis for patients with intrahepatic cholangiocarcinoma: systematic review and meta-analysis. JAMA Surg, 149(6):565-574. https://doi.org/10.1001/jamasurg.2013.5137

    Article  PubMed  Google Scholar 

  6. Zhang H, Yang T, Wu M, Shen F. (2016) Intrahepatic cholangiocarcinoma: Epidemiology, risk factors, diagnosis and surgical management. Cancer Lett, 379(2):198-205. https://doi:https://doi.org/10.1016/j.canlet.2015.09.008

    Article  CAS  PubMed  Google Scholar 

  7. Bruix J, Sherman M. (2005) Management of hepatocellular carcinoma. Hepatology, 42(5):1208-1236. https://doi.org/10.1002/hep.20933

    Article  PubMed  Google Scholar 

  8. Claudon M, Dietrich CF, Choi BI, Cosgrove DO, Kudo M, Nolsøe CP, et al. (2013) Guidelines and good clinical practice recommendations for contrast enhanced ultrasound (CEUS) in the liver--update 2012: a WFUMB-EFSUMB initiative in cooperation with representatives of AFSUMB, AIUM, ASUM, FLAUS and ICUS. Ultraschall Med, 34(1):11-29. https://doi.org/10.1055/s-0032-1325499

    Article  CAS  PubMed  Google Scholar 

  9. Joo I, Lee JM, Yoon JH. (2018) Imaging diagnosis of intrahepatic and perihilar cholangiocarcinoma: recent advances and challenges. Radiology, 288(1):7-13. https://doi.org/10.1148/radiol.2018171187

    Article  PubMed  Google Scholar 

  10. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. Eur J Cancer 2012; 48(5):599-641. https://doi.org/10.1016/j.ejca.2011.12.021

    Article  Google Scholar 

  11. Kono Y, Lyshchik A, Cosgrove D, Dietrich CF, Jang HJ, Kim TK, Piscaglia F, Willmann JK, Wilson SR, Santillan C, Kambadakone A, Mitchell D, Vezeridis A, Sirlin CB. (2017) Contrast Enhanced Ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS®): the official version by the American College of Radiology (ACR). Ultraschall Med, 38(1):85-86. https://doi.org/10.1055/s-0042-124369

    Article  PubMed  Google Scholar 

  12. Terzi E, Iavarone M, Pompili M, Veronese L, Cabibbo G, Fraquelli M, Riccardi L, De Bonis L, Sangiovanni A, Leoni S, Zocco MA, Rossi S, Alessi N, Wilson SR, Piscaglia F. (2018) Contrast ultrasound LI-RADS LR-5 identifies hepatocellular carcinoma in cirrhosis in a multicenter restropective study of 1,006 nodules. J Hepatol, 68(3):485-492. https://doi.org/10.1016/j.jhep.2017.11.007

    Article  PubMed  Google Scholar 

  13. Li F, Li Q, Liu Y, Han J, Zheng W, Huang Y, Zheng X, Cao L, Zhou JH. (2020) Distinguishing intrahepatic cholangiocarcinoma from hepatocellular carcinoma in patients with and without risks: the evaluation of the LR-M criteria of contrast-enhanced ultrasound liver imaging reporting and data system version 2017. Eur Radiol, 30(1):461-470. https://doi.org/10.1007/s00330-019-06317-2

    Article  PubMed  Google Scholar 

  14. Jiang W, Zeng ZC, Tang ZY, Fan J, Sun HC, Zhou J, Zeng MS, Zhang BH, Ji Y, Chen YX. (2011) A prognostic scoring system based on clinical features of intrahepatic cholangiocarcinoma: the Fudan score. Ann Oncol, 22(7):1644-1652. https://doi.org/10.1093/annonc/mdq650

    Article  CAS  PubMed  Google Scholar 

  15. Mavros MN, Economopoulos KP, Alexiou VG, Pawlik TM. (2014) Treatment and prognosis for patients with intrahepatic cholangiocarcinoma: systematic review and meta-analysis. JAMA Surg, 149:565–574. https://doi.org/10.1001/jamasurg.2013.5137

    Article  PubMed  Google Scholar 

  16. Zeng D, Xu M, Liang JY, Cheng MQ, Huang H, Pan JM, Huang Y, Tong WJ, Xie XY, Lu MD, Kuang M, Chen LD, Hu HT, Wang W. (2022) Using new criteria to improve the differentiation between HCC and non-HCC malignancies: clinical practice and discussion in CEUS LI-RADS 2017. Radiol Med, 127 (1), 1-10. https://doi.org/10.1007/s11547-021-01417-w

    Article  PubMed  Google Scholar 

  17. Huang JY, Li JW, Ling WW, Li T, Luo Y, Liu JB, Lu Q. (2020) Can contrast enhanced ultrasound differentiate intrahepatic cholangiocarcinoma from hepatocellular carcinoma? World J Gastroenterol, 26(27):3938-3951. https://doi.org/10.3748/wjg.v26.i27.3938

    Article  PubMed  PubMed Central  Google Scholar 

  18. Chen LD, Xu HX, Xie XY, Xie XH, Xu ZF, Liu GJ, Wang Z, Lin MX, Lu MD. (2010) Intrahepatic cholangiocarcinoma and hepatocellular carcinoma: differential diagnosis with contrast-enhanced ultrasound. Eur Radiol, 20(3):743-753. https://doi.org/10.1007/s00330-009-1599-8

    Article  CAS  PubMed  Google Scholar 

  19. Chen LD, Ruan SM, Liang JY, Yang Z, Shen SL, Huang Y, Li W, Wang Z, Xie XY, Lu MD, Kuang M, Wang W. (2018) Differentiation of intrahepatic cholangiocarcinoma from hepatocellular carcinoma in high-risk patients: a predictive model using contrast-enhanced ultrasound. World J Gastroenterol, 24(33):3786-3798. https://doi.org/10.3748/wjg.v24.i33.3786

    Article  PubMed  PubMed Central  Google Scholar 

  20. Liu GJ, Wang W, Lu MD, Xie XY, Xu HX, Xu ZF, Chen LD, Wang Z, Liang JY, Huang Y, Li W, Liu JY. (2015) Contrast-enhanced ultrasound for the characterization of hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Liver Cancer, 4(4):241-252. https://doi.org/10.1159/000367738

    Article  PubMed  PubMed Central  Google Scholar 

  21. Xu HX, Chen LD, Liu LN, Zhang YF, Guo LH, Liu C. (2012) Contrast-enhanced ultrasound of intrahepatic cholangiocarcinoma: correlation with pathological examination. Br J Radiol, 85(1016):1029-1037. https://doi.org/10.1259/bjr/21653786

    Article  PubMed  PubMed Central  Google Scholar 

  22. Yuan MX, Li R, Zhang XH, Tang CL, Guo YL, Guo DY, Luo MK. (2016) Factors affecting the enhancement patterns of intrahepatic cholangiocarcinoma (ICC) on contrast-enhanced ultrasound (CEUS) and their pathological correlations in patients with a single lesion. Ultraschall Med, 37(6):609-618. https://doi.org/10.1055/s-0034-1399485

    Article  CAS  PubMed  Google Scholar 

  23. Han J, Liu Y, Han F, Li Q, Yan C, Zheng W, Wang J, Guo Z, Wang J, Li A, Zhou J. (2015) The degree of contrast washout on contrast-enhanced ultrasound in distinguishing intrahepatic cholangiocarcinoma from hepatocellular carcinoma. Ultrasound Med Biol, 41(12):3088-3095. https://doi.org/10.1016/j.ultrasmedbio.2015.08.001

    Article  PubMed  Google Scholar 

  24. Kong WT, Wang WP, Huang BJ, Ding H, Mao F. (2014) Value of wash-in and wash-out time in the diagnosis between hepatocellular carcinoma and other hepatic nodules with similar vascular pattern on contrast-enhanced ultrasound. J Gastroenterol Hepatol, 29(3):576-580. https://doi.org/10.1111/jgh.12394

    Article  PubMed  Google Scholar 

  25. Li R, Yuan MX, Ma KS, Li XW, Tang CL, Zhang XH, Guo DY, Yan XC. (2014) Detailed analysis of temporal features on contrast enhanced ultrasound may help differentiate intrahepatic cholangiocarcinoma from hepatocellular carcinoma in cirrhosis. PLoS One, 9(5):e98612. https://doi.org/10.1371/journal.pone.0098612

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Zheng W, Li Q, Zou XB, Wang JW, Han F, Li F, Huang LS, Li AH, Zhou JH. (2020) Evaluation of Contrast-enhanced US LI-RADS version 2017: Application on 2020 Liver Nodules in Patients with Hepatitis B Infection. Radiology, 294(2):299–307. https://doi.org/10.1148/radiol.2019190878

    Article  PubMed  Google Scholar 

  27. Chan KM, Tsai CY, Yeh CN, Yeh TS, Lee WC, Jan YY, Chen MF. (2018) Characterization of intrahepatic cholangiocarcinoma after curative resection: outcome, prognostic factor, and recurrence. BMC Gastroenterol, 18(1):180. https://doi.org/10.1186/s12876-018-0912-x

    Article  PubMed  PubMed Central  Google Scholar 

  28. Izquierdo-Sanchez L, Lamarca A, La Casta A, Buettner S, Utpatel K, Klümpen HJ, et al. (2022) Cholangiocarcinoma landscape in Europe: diagnostic, prognostic and therapeutic insights from the ENSCCA Registry. J Hepatol, 76(5):1109-1121. https://doi.org/10.1016/j.jhep.2021.12.010

    Article  CAS  PubMed  Google Scholar 

  29. Chen VL, Sharma P. (2020) Role of biomarkers and biopsy in hepatocellular carcinoma. Clin Liver Dis, 24(4):577-590. https://doi.org/10.1016/j.cld.2020.07.001

    Article  PubMed  Google Scholar 

  30. Zheng Y, Zhu M, Li M. (2020) Effects of alpha-fetoprotein on the occurrence and progression of hepatocellular carcinoma. J Cancer Res Clin Oncol, 146(10):2439-2446. https://doi.org/10.1007/s00432-020-03331-6

    Article  CAS  PubMed  Google Scholar 

  31. American College of Radiology. CT/MRI LI-RADS v2018 core. Published 2018. Accessed February 5, 2022. https://www.acr.org/-/media/ACR/Files/RADS/LI-RADS/LI-RADS-2018-Core

Download references

Acknowledgements

We would like to acknowledge the effort and support of all authors in the study.

Funding

This work was supported in part by the National Natural Science Foundation of China (Grant 82202174), the Science and Technology Commission of Shanghai Municipality (Grant 19DZ2251100), Shanghai Municipal Health Commission (Grant SHSLCZDZK03502), Shanghai Science and Technology Innovation Action Plan (21Y11911200), and Fundamental Research Funds for the Central Universities (ZD-11-202151), Scientific Research and Development Fund of Zhongshan Hospital of Fudan University (Grant 2022ZSQD07).

Author information

Author notes

  1. Li-Fan Wang and Xin Guan have contributed equally to this work.

Authors and Affiliations

  1. Department of Ultrasound, Zhongshan Hospital, Institute of Ultrasound in Medicine and Engineering, Fudan University, Shanghai, 200032, China

    Li-Fan Wang, Bo-Yang Zhou, Yi-Kang Sun, Xiao-Long Li, Hao-Hao Yin, Dan Lu, Xin Ye, Han-Sheng Xia, Xi Wang, Qing Lu, Hong Han, Hui-Xiong Xu & Chong-Ke Zhao

  2. Department of Medical Ultrasound, Center of Minimally Invasive Treatment for Tumor, Shanghai Tenth People’s Hospital, Ultrasound Research and Education Institute, School of Medicine, Tongji University, Shanghai, 200072, China

    Xin Guan & Yu-Ting Shen

  3. Shanghai Institute of Medical Imaging, Shanghai, 200032, China

    Li-Fan Wang, Bo-Yang Zhou, Yi-Kang Sun, Xiao-Long Li, Hao-Hao Yin, Dan Lu, Xin Ye, Han-Sheng Xia, Xi Wang, Hong Han, Hui-Xiong Xu & Chong-Ke Zhao

  4. School of Medicine, Anhui University of Science and Technology, Anhu, 232000, China

    Xin-Yuan Hu

  5. Department of Ultrasound, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, 361006, China

    Dao-Hui Yang & Qing Lu

Authors
  1. Li-Fan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xin Guan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yu-Ting Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bo-Yang Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yi-Kang Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xiao-Long Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hao-Hao Yin
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Dan Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Xin Ye
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Xin-Yuan Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Dao-Hui Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Han-Sheng Xia
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Xi Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Qing Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Hong Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Hui-Xiong Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Chong-Ke Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

China Alliance of Multi-Center Clinical Study for Ultrasound (Ultra-Chance)

Contributions

WLF, GX, SYT and ZCK: study design; WLF and ZBY: statistical analysis; SYK, LXL, YDH and LQ: data collection and data interpretation; WLF: writing of the first draft of the paper; ZCK and XHX: revision of the manuscript; YHH, LD, YX, HXY, XHS, WX and HH: providing administrative, technical and material support; XHX and ZCK: supervising the study.

Corresponding authors

Correspondence to Hui-Xiong Xu or Chong-Ke Zhao.

Ethics declarations

Conflict of interest

These authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article.

Ethical approval

Institutional Review Board approval was obtained (B2022-569R).

Informed consent

Informed consent from patients was waived for the retrospective nature of the study by the Institutional Review Board.

Additional information

Publisher's Note

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

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 20 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, LF., Guan, X., Shen, YT. et al. A multi-parameter intrahepatic cholangiocarcinoma scoring system based on modified contrast-enhanced ultrasound LI-RADS M criteria for differentiating intrahepatic cholangiocarcinoma from hepatocellular carcinoma. Abdom Radiol 49, 458–470 (2024). https://doi.org/10.1007/s00261-023-04114-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00261-023-04114-6

Keywords

Search

Navigation