Skip to main content

Advertisement

SpringerLink
Log in

Nomogram based on Sonazoid contrast-enhanced ultrasound to differentiate intrahepatic cholangiocarcinoma and poorly differentiated hepatocellular carcinoma: a prospective multicenter study

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

Abstract

Objectives

The aim of this study was to develop a predictive model based on Sonazoid contrast-enhanced ultrasound (SCEUS) and clinical features to discriminate poorly differentiated hepatocellular carcinoma (P-HCC) from intrahepatic cholangiocarcinoma (ICC).

Patients and method

Forty-one ICC and forty-nine P-HCC patients were enrolled in this study. The CEUS LI-RADS category was assigned according to CEUS LI-RADS version 2017. Based on SCEUS and clinical features, a predicated model was established. Multivariate logistic regression analysis and LASSO logistic regression were used to identify the most valuable features, 400 times repeated 3-fold cross-validation was performed on the nomogram model and the model performance was determined by its discrimination, calibration, and clinical usefulness.

Results

Multivariate logistic regression and LASSO logistic regression indicated that age (> 51 y), viral hepatitis (No), AFP level (≤  20 µg/L), washout time (≤  45 s), and enhancement level in the Kupffer phase (Defect) were valuable predictors related to ICC. The area under the receiver operating characteristic (AUC) of the nomogram was 0.930 (95% CI: 0.856–0.973), much higher than the subjective assessment by the sonographers and CEUS LI-RADS categories. The calibration curve showed that the predicted incidence was more consistent with the actual incidence of ICC, and 400 times repeated 3-fold cross-validation revealed good discrimination with a mean AUC of 0.851. Decision curve analysis showed that the nomogram could increase the net benefit for patients.

Conclusions

The nomogram based on SCEUS and clinical features can effectively differentiate P-HCC from ICC

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
Fig. 7

Similar content being viewed by others

Abbreviations

AP:

Arterial phase

AUC:

Area under the receiver operating characteristic

CEUS:

Contrast-enhanced ultrasound

CI:

Confidence interval

HCC:

Hepatocellular carcinoma

ICC:

Intrahepatic cholangiocarcinoma

KP:

Kupffer phase

OR:

Odds ratio

P-HCC:

Poorly differentiated hepatocellular carcinoma

ROI:

Region of interest

SCEUS:

Sonazoid contrast-enhanced ultrasound

References

  1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 2021;71:209-249.

    Article  PubMed  Google Scholar 

  2. Sahu SK, Chawla YK, Dhiman RK, Singh V, Duseja A, Taneja S, Kalra N, et al. Rupture of Hepatocellular Carcinoma: A Review of Literature. J Clin Exp Hepatol 2019;9:245-256.

    Article  PubMed  Google Scholar 

  3. European Association for the Study of the Liver Ea, easloffice easloffice eu, European Association for the Study of the L. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol 2018;69:182-236.

  4. Kudo M, Trevisani F, Abou-Alfa GK, Rimassa L. Hepatocellular Carcinoma: Therapeutic Guidelines and Medical Treatment. Liver Cancer 2016;6:16-26.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Wang K, Zhang H, Xia Y, Liu J, Shen F. Surgical options for intrahepatic cholangiocarcinoma. Hepatobiliary Surg Nutr 2017;6:79-90.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Patrone R, Izzo F, Palaia R, Granata V, Nasti G, Ottaiano A, Pasta G, et al. Minimally invasive surgical treatment of intrahepatic cholangiocarcinoma: A systematic review. World J Gastrointest Oncol 2021;13:2203-2215.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Galassi M, Iavarone M, Rossi S, Bota S, Vavassori S, Rosa L, Leoni S, et al. Patterns of appearance and risk of misdiagnosis of intrahepatic cholangiocarcinoma in cirrhosis at contrast enhanced ultrasound. Liver Int 2013;33:771-779.

    Article  CAS  PubMed  Google Scholar 

  8. Little JM, Richardson A, Tait N. Hepatic dystychoma: a five year experience. HPB Surg 1991;4:291-297.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Boozari B, Soudah B, Rifai K, Schneidewind S, Vogel A, Hecker H, Hahn A, et al. Grading of hypervascular hepatocellular carcinoma using late phase of contrast enhanced sonography - a prospective study. Dig Liver Dis 2011;43:484-490.

    Article  PubMed  Google Scholar 

  10. Jang HJ, Kim TK, Burns PN, Wilson SR. Enhancement patterns of hepatocellular carcinoma at contrast-enhanced US: comparison with histologic differentiation. Radiology 2007;244:898-906.

    Article  PubMed  Google Scholar 

  11. Hatanaka K, Kudo M, Minami Y, Maekawa K. Sonazoid-enhanced ultrasonography for diagnosis of hepatic malignancies: comparison with contrast-enhanced CT. Oncology 2008;75 Suppl 1:42-47.

    Article  PubMed  Google Scholar 

  12. Sugimoto K, Moriyasu F, Saito K, Taira J, Saguchi T, Yoshimura N, Oshiro H, et al. Comparison of Kupffer-phase Sonazoid-enhanced sonography and hepatobiliary-phase gadoxetic acid-enhanced magnetic resonance imaging of hepatocellular carcinoma and correlation with histologic grading. J Ultrasound Med 2012;31:529-538.

    Article  PubMed  Google Scholar 

  13. Li C, Xu J, Liu Y, Wu M, Dai W, Song J, Wang H. Kupffer Phase Radiomics Signature in Sonazoid-Enhanced Ultrasound is an Independent and Effective Predictor of the Pathologic Grade of Hepatocellular Carcinoma. J Oncol 2022;2022:6123242.

    PubMed  PubMed Central  Google Scholar 

  14. Dietrich CF, Nolsoe CP, Barr RG, Berzigotti A, Burns PN, Cantisani V, Chammas MC, et al. Guidelines and Good Clinical Practice Recommendations for Contrast-Enhanced Ultrasound (CEUS) in the Liver-Update 2020 WFUMB in Cooperation with EFSUMB, AFSUMB, AIUM, and FLAUS. Ultrasound Med Biol 2020;46:2579-2604.

    Article  PubMed  Google Scholar 

  15. Washington MK, Goldberg RM, Chang GJ, Limburg P, Lam AK, Salto-Tellez M, Arends MJ, et al. Diagnosis of digestive system tumours. Int J Cancer 2021;148:1040-1050.

    Article  CAS  PubMed  Google Scholar 

  16. Lee JY, Minami Y, Choi BI, Lee WJ, Chou YH, Jeong WK, Park MS, et al. The AFSUMB Consensus Statements and Recommendations for the Clinical Practice of Contrast-Enhanced Ultrasound using Sonazoid. Ultrasonography 2020;39:191-220.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Radiology ACo. CEUS LI-RADS version 2017. In: American College of Radiology; 2017.

  18. Cannella R, Furlan A. Mosaic architecture of hepatocellular carcinoma. Abdom Radiol (NY) 2018;43:1847-1848.

    Article  PubMed  Google Scholar 

  19. Dietrich CF, Dong Y, Kono Y, Caraiani C, Sirlin CB, Cui XW, Tang A. LI-RADS ancillary features on contrast-enhanced ultrasonography. Ultrasonography 2020;39:221-228.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Kang HJ, Kim JH, Yoo J, Han JK. Diagnostic criteria of perfluorobutane-enhanced ultrasonography for diagnosing hepatocellular carcinoma in high-risk individuals: how is late washout determined? Ultrasonography 2022;41:530-542.

    Article  PubMed  Google Scholar 

  21. Li L, Zheng W, Wang J, Han J, Guo Z, Hu Y, Li X, et al. Contrast-Enhanced Ultrasound Using Perfluorobutane: Impact of Proposed Modified LI-RADS Criteria on Hepatocellular Carcinoma Detection. AJR Am J Roentgenol 2022;219:434-443.

    Article  PubMed  Google Scholar 

  22. Huang Z, Zhou P, Li S, Li K. Evaluation of contrast-enhanced ultrasound LI-RADS version 2017: application on 271 liver nodules in individuals with non-alcoholic steatohepatitis. Eur Radiol 2022.

  23. Matsumoto N, Ogawa M, Takayasu K, Hirayama M, Miura T, Shiozawa K, Abe M, et al. Quantitative sonographic image analysis for hepatic nodules: a pilot study. J Med Ultrason (2001) 2015;42:505-512.

    Google Scholar 

  24. Yanagisawa K, Moriyasu F, Miyahara T, Yuki M, Iijima H. Phagocytosis of ultrasound contrast agent microbubbles by Kupffer cells. Ultrasound Med Biol 2007;33:318-325.

    Article  PubMed  Google Scholar 

  25. Shunichi S, Hiroko I, Fuminori M, Waki H. Definition of contrast enhancement phases of the liver using a perfluoro-based microbubble agent, perflubutane microbubbles. Ultrasound Med Biol 2009;35:1819-1827.

    Article  PubMed  Google Scholar 

  26. Barr RG, Huang P, Luo Y, Xie X, Zheng R, Yan K, Jing X, et al. Contrast-enhanced ultrasound imaging of the liver: a review of the clinical evidence for SonoVue and Sonazoid. Abdom Radiol (NY) 2020;45:3779-3788.

    Article  PubMed  Google Scholar 

  27. Korenaga K, Korenaga M, Furukawa M, Yamasaki T, Sakaida I. Usefulness of Sonazoid contrast-enhanced ultrasonography for hepatocellular carcinoma: comparison with pathological diagnosis and superparamagnetic iron oxide magnetic resonance images. J Gastroenterol 2009;44:733-741.

    Article  PubMed  Google Scholar 

  28. Zou RH, Lin QG, Huang W, Li XL, Cao Y, Zhang J, Zhou JH, et al. Quantitative Contrast-Enhanced Ultrasonic Imaging Reflects Microvascularization in Hepatocellular Carcinoma and Prognosis after Resection. Ultrasound Med Biol 2015;41:2621-2630.

    Article  PubMed  Google Scholar 

  29. Lv K, Zhai H, Jiang Y, Liang P, Xu HX, Du L, Chou YH, et al. Prospective assessment of diagnostic efficacy and safety of Sonazoid(TM) and SonoVue((R)) ultrasound contrast agents in patients with focal liver lesions. Abdom Radiol (NY) 2021;46:4647-4659.

    Article  PubMed  Google Scholar 

  30. Sugimoto K, Kakegawa T, Takahashi H, Tomita Y, Abe M, Yoshimasu Y, Takeuchi H, et al. Usefulness of Modified CEUS LI-RADS for the Diagnosis of Hepatocellular Carcinoma Using Sonazoid. Diagnostics (Basel) 2020;10.

  31. Guo HL, Zheng X, Cheng MQ, Zeng D, Huang H, Xie XY, Lu MD, et al. Contrast-Enhanced Ultrasound for Differentiation Between Poorly Differentiated Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma. J Ultrasound Med 2022;41:1213-1225.

    Article  PubMed  Google Scholar 

  32. Yuan M, Li R, Zhang Y, Yang L, Zhang X, Tang C, Guo D. Enhancement Patterns of Intrahepatic Cholangiocarcinoma on Contrast-Enhanced Ultrasound: Correlation with Clinicopathologic Findings and Prognosis. Ultrasound Med Biol 2019;45:26-34.

    Article  PubMed  Google Scholar 

  33. Zheng W, Li Q, Zou XB, Wang JW, Han F, Li F, Huang LS, et al. Evaluation of Contrast-enhanced US LI-RADS version 2017: Application on 2020 Liver Nodules in Patients with Hepatitis B Infection. Radiology 2020;294:299-307.

    Article  PubMed  Google Scholar 

Download references

Funding

This study was funded by the National Scientific Foundation Committee of China (Grants 82172027).

Author information

Author notes

  1. Shuo Wang and Jundong Yao have contributed equally to this work.

Authors and Affiliations

  1. Department of Interventional Ultrasound, First Medical Center of Chinese PLA General Hospital, No.28 Fuxing Road, Beijing, 100853, China

    Shuo Wang, Jundong Yao, Yunlin Li, Erpeng Qi, Yiqiong Zhang & Xiaoling Yu

  2. Chinese PLA Medical School, Beijing, 100853, China

    Shuo Wang

  3. Department of Ultrasound, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, 471000, China

    Jundong Yao

  4. Department of Ultrasound, Affiliated Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Kaiyan Li

  5. Department of Ultrasound, The First Affiliated Hospital of Guangxi medical University, Nanning, 530021, China

    Hong Yang

  6. Department of Hepatobiliary Surgery, First Medical Center of Chinese PLA General Hospital, Beijing, 100853, China

    Shichun Lu

  7. Department of Ultrasound, University of Chinese Academy of Sciences Shenzhen Hospital, Guangming District, Shenzhen, 518000, China

    Guangzhi He

  8. Department of Ultrasound, Peking University Cancer Hospital & Institute, Beijing, 100142, China

    Wei Wu

  9. Department of Ultrasonography, Harbin Medical University Cancer Hospital, Harbin, 150000, China

    Wen Cheng

  10. Department of Ultrasound Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, China

    Tianan Jiang

  11. Department of Ultrasound, Huashan Hospital, Fudan University, Shanghai, 200040, China

    Hong Ding

  12. Department of Ultrasound, Tianjin Third Central Hospital, Tianjin, 300170, China

    Xiang Jing

  13. Department of Ultrasound, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Henan, 450007, China

    Yuanyuan Yan

  14. Department of Interventional Ultrasound, Fifth Medical Center of ChinesePLA General Hospital, No.28 Fuxing Road, Beijing, 100853, China

    Fangyi Liu, Jie Yu, Zhiyu Han, Zhigang Cheng, Shuilian Tan, Xin Li, Jianping Dou & Ping Liang

Authors
  1. Shuo Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jundong Yao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kaiyan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hong Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shichun Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Guangzhi He
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Wei Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Wen Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Tianan Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Hong Ding
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Xiang Jing
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Yuanyuan Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Fangyi Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Jie Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Zhiyu Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Zhigang Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Shuilian Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Xin Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Jianping Dou
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Yunlin Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Erpeng Qi
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Yiqiong Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Ping Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. Xiaoling Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the study conception and design. The first draft of the manuscript was written by SW and all authors commented on the previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Ping Liang or Xiaoling Yu.

Ethics declarations

Competing interest

The authors have no relevant financial or non-financial interests to disclose.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This study was approved by the Institutional Review Boards at each center (S2020-300-01)

Consent to participate

Informed consent was obtained from all individual participants included in the study.

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 36 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, S., Yao, J., Li, K. et al. Nomogram based on Sonazoid contrast-enhanced ultrasound to differentiate intrahepatic cholangiocarcinoma and poorly differentiated hepatocellular carcinoma: a prospective multicenter study. Abdom Radiol 48, 3101–3113 (2023). https://doi.org/10.1007/s00261-023-03993-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00261-023-03993-z

Keywords

Search

Navigation