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A preoperative scoring system to predict lymph node metastasis in intrahepatic cholangiocarcinoma

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Abstract

Background

The abnormality of imaging finding of lymph node (LN) has demonstrated unsatisfactory diagnostic accuracy for pathologic lymph node metastasis (LNM). We aimed to develop and validate a simple scoring system predicting LNM in patients with intrahepatic cholangiocarcinoma (iCCA) prior to surgery based on MRI and clinical findings.

Methods

We retrospectively enrolled consecutive patients who underwent surgical resection for treatment-naïve iCCA from six institutions between January 2009 and December 2015. Patients who underwent lymph node dissection (LND) were randomly assigned to the training and validation cohorts at a 2:1 ratio, an¹ìd pathologic LN status was evaluated. Patients who did not undergo LND were assigned to the test cohort, and clinical LN status was evaluated. Using MRI and clinical findings, a preoperative LNM score was developed in the training cohort and validated in the validation and test cohorts.

Results

The training, validation, and test cohorts included 102, 53, and 118 patients, respectively. The preoperative LNM score consisted of serum carcinoembryonic antigen and two MRI findings (suspicious LN and bile duct invasion). The preoperative LNM score was associated with pathologic LNM in training (p < 0.001) and validation (p = 0.010) cohorts and clinical LNM in test cohort (p < 0.001). The preoperative LNM score outperformed MRI-suspicious LN alone in predicting pathologic LNM (area under the curve, 0.703 vs. 0.604, p = 0.004). The preoperative LNM score was also associated with overall survival in all cohorts (p < 0.001).

Conclusions

Our preoperative LNM score was significantly associated with pathologic or clinical LNM and outperformed MRI-suspicious LN alone.

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References

  1. Spolverato G, Kim Y, Alexandrescu S, Marques HP, Lamelas J, Aldrighetti L, et al. Management and outcomes of patients with recurrent intrahepatic cholangiocarcinoma following previous curative-intent surgical resection. Ann Surg Oncol. 2016;23(1):235–243. https://doi.org/10.1245/s10434-015-4642-9

    Article  PubMed  Google Scholar 

  2. Banales JM, Marin JJG, Lamarca A, Rodrigues PM, Khan SA, Roberts LR, et al. Cholangiocarcinoma 2020: the next horizon in mechanisms and management. Nat Rev Gastroenterol Hepatol. 2020;17(9):557–588. https://doi.org/10.1038/s41575-020-0310-z

    Article  PubMed  PubMed Central  Google Scholar 

  3. Kim BW, Oh CM, Choi HY, Park JW, Cho H, Ki M. Incidence and overall survival of biliary tract cancers in South Korea from 2006 to 2015: Using the National Health Information Database. Gut Liver. 2019;13(1):104–113. https://doi.org/10.5009/gnl18105

    Article  PubMed  Google Scholar 

  4. Bridgewater J, Galle PR, Khan SA, Llovet JM, Park JW, Patel T, et al. Guidelines for the diagnosis and management of intrahepatic cholangiocarcinoma. J Hepatol. 2014;60(6):1268–1289. https://doi.org/10.1016/j.jhep.2014.01.021

    Article  PubMed  Google Scholar 

  5. de Jong MC, Nathan H, Sotiropoulos GC, Paul A, Alexandrescu S, Marques H, et al. Intrahepatic cholangiocarcinoma: an international multi-institutional analysis of prognostic factors and lymph node assessment. J Clin Oncol. 2011;29(23):3140–3145. https://doi.org/10.1200/JCO.2011.35.6519

    Article  PubMed  Google Scholar 

  6. Adachi T, Eguchi S, Beppu T, Ueno S, Shiraishi M, Okuda K, et al. Prognostic impact of preoperative lymph node enlargement in intrahepatic cholangiocarcinoma: a multi-institutional study by the kyushu study group of liver surgery. Ann Surg Oncol. 2015;22(7):2269–2278. https://doi.org/10.1245/s10434-014-4239-8

    Article  PubMed  Google Scholar 

  7. Grobmyer SR, Wang L, Gonen M, Fong Y, Klimstra D, D’Angelica M, et al. Perihepatic lymph node assessment in patients undergoing partial hepatectomy for malignancy. Ann Surg. 2006;244(2):260–264. https://doi.org/10.1097/01.sla.0000217606.59625.9d

    Article  PubMed  PubMed Central  Google Scholar 

  8. Noji T, Kondo S, Hirano S, Tanaka E, Suzuki O, Shichinohe T. Computed tomography evaluation of regional lymph node metastases in patients with biliary cancer. Br J Surg. 2008;95(1):92–96. https://doi.org/10.1002/bjs.5920

    Article  CAS  PubMed  Google Scholar 

  9. Choi SB, Kim KS, Choi JY, Park SW, Choi JS, Lee WJ, et al. The prognosis and survival outcome of intrahepatic cholangiocarcinoma following surgical resection: association of lymph node metastasis and lymph node dissection with survival. Ann Surg Oncol. 2009;16(11):3048–3056. https://doi.org/10.1245/s10434-009-0631-1

    Article  PubMed  Google Scholar 

  10. Mahul BASBE, Frederick LG, David RB, Robert KB, Mary KW, Jeffrey EG, Carolyn CC, Kenneth RH, Daniel CS, Milburn JJ, James DB, Lauri EG, Richard LS, Charles MB, David PW, Elliot AA, Martin M, Donna MG, Laura RM (2017) In: AJCC Cancer Staging Manual. 8th edition. Springer, New York

  11. Weber SM, Ribero D, O’Reilly EM, Kokudo N, Miyazaki M, Pawlik TM. Intrahepatic cholangiocarcinoma: expert consensus statement. HPB (Oxford). 2015;17(8):669–680. https://doi.org/10.1111/hpb.12441

    Article  PubMed  Google Scholar 

  12. Valle JW, Borbath I, Khan SA, Huguet F, Gruenberger T, Arnold D, et al. Biliary cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016;27(suppl 5):v28–v37. https://doi.org/10.1093/annonc/mdw324

    Article  CAS  PubMed  Google Scholar 

  13. Clark CJ, Wood-Wentz CM, Reid-Lombardo KM, Kendrick ML, Huebner M, Que FG. Lymphadenectomy in the staging and treatment of intrahepatic cholangiocarcinoma: a population-based study using the National Cancer Institute SEER database. HPB (Oxford). 2011;13(9):612–620. https://doi.org/10.1111/j.1477-2574.2011.00340.x

    Article  PubMed  Google Scholar 

  14. Zhou R, Lu D, Li W, Tan W, Zhu S, Chen X, et al. Is lymph node dissection necessary for resectable intrahepatic cholangiocarcinoma? A systematic review and meta-analysis. HPB (Oxford). 2019;21(7):784–792. https://doi.org/10.1016/j.hpb.2018.12.011

    Article  PubMed  Google Scholar 

  15. Nakanuma Y, Klimstra D, Komuta M, Zen Y (2019) Intrahepatic cholangiocarcinoma. WHO Classification of Tumours of the Digestive System, 254–259

  16. Akita M, Sofue K, Fujikura K, Otani K, Itoh T, Ajiki T, et al. Histological and molecular characterization of intrahepatic bile duct cancers suggests an expanded definition of perihilar cholangiocarcinoma. HPB (Oxford). 2019;21(2):226–234. https://doi.org/10.1016/j.hpb.2018.07.021

    Article  PubMed  Google Scholar 

  17. Liau JY, Tsai JH, Yuan RH, Chang CN, Lee HJ, Jeng YM. Morphological subclassification of intrahepatic cholangiocarcinoma: etiological, clinicopathological, and molecular features. Mod Pathol. 2014;27(8):1163–1173. https://doi.org/10.1038/modpathol.2013.241

    Article  CAS  PubMed  Google Scholar 

  18. Akita M, Fujikura K, Ajiki T, Fukumoto T, Otani K, Azuma T, et al. Dichotomy in intrahepatic cholangiocarcinomas based on histologic similarities to hilar cholangiocarcinomas. Mod Pathol. 2017;30(7):986–997. https://doi.org/10.1038/modpathol.2017.22

    Article  CAS  PubMed  Google Scholar 

  19. Rhee H, Choi SH, Park JH, Cho ES, Yeom SK, Park S, et al. Preoperative magnetic resonance imaging-based prognostic model for mass-forming intrahepatic cholangiocarcinoma. Liver Int. 2022. https://doi.org/10.1111/liv.15196

    Article  PubMed  Google Scholar 

  20. Lee W, Jeong CY, Jang JY, Roh YH, Kim KW, Kang SH, et al. Clinical implication of tumor site in terms of node metastasis for intrahepatic cholangiocarcinoma. Eur J Surg Oncol. 2020;46(5):832–838. https://doi.org/10.1016/j.ejso.2019.11.511

    Article  PubMed  Google Scholar 

  21. Navarro JG, Lee JH, Kang I, Rho SY, Choi GH, Han DH, et al. Prognostic significance of and risk prediction model for lymph node metastasis in resectable intrahepatic cholangiocarcinoma: do all require lymph node dissection? HPB (Oxford). 2020;22(10):1411–1419. https://doi.org/10.1016/j.hpb.2020.01.009

    Article  PubMed  Google Scholar 

  22. Rhee H, Kim MJ, Park YN, An C. A proposal of imaging classification of intrahepatic mass-forming cholangiocarcinoma into ductal and parenchymal types: clinicopathologic significance. Eur Radiol. 2019;29(6):3111–3121. https://doi.org/10.1007/s00330-018-5898-9

    Article  PubMed  Google Scholar 

  23. Nam JG, Lee JM, Joo I, Ahn SJ, Park JY, Lee KB, et al. Intrahepatic mass-forming cholangiocarcinoma: relationship between computed tomography characteristics and histological subtypes. J Comput Assist Tomogr. 2018;42(3):340–349. https://doi.org/10.1097/RCT.0000000000000695

    Article  PubMed  Google Scholar 

  24. Loosen SH, Roderburg C, Kauertz KL, Koch A, Vucur M, Schneider AT, et al. CEA but not CA19-9 is an independent prognostic factor in patients undergoing resection of cholangiocarcinoma. Sci Rep. 2017;7(1):16975. https://doi.org/10.1038/s41598-017-17175-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Wang K, Jiang X, Ren Y, Ma Z, Cheng X, Li F, et al. The significance of preoperative serum carcinoembryonic antigen levels in the prediction of lymph node metastasis and prognosis in locally advanced gastric cancer: a retrospective analysis. BMC Gastroenterol. 2020;20(1):100. https://doi.org/10.1186/s12876-020-01255-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Bergquist JR, Ivanics T, Storlie CB, Groeschl RT, Tee MC, Habermann EB, et al. Implications of CA19-9 elevation for survival, staging, and treatment sequencing in intrahepatic cholangiocarcinoma: a national cohort analysis. J Surg Oncol. 2016;114(4):475–482. https://doi.org/10.1002/jso.24381

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Tsilimigras DI, Sahara K, Paredes AZ, Moro A, Mehta R, Moris D, et al. Predicting lymph node metastasis in intrahepatic cholangiocarcinoma. J Gastrointest Surg. 2021;25(5):1156–1163. https://doi.org/10.1007/s11605-020-04720-5

    Article  PubMed  Google Scholar 

  28. Ji GW, Zhu FP, Zhang YD, Liu XS, Wu FY, Wang K, et al. A radiomics approach to predict lymph node metastasis and clinical outcome of intrahepatic cholangiocarcinoma. Eur Radiol. 2019;29(7):3725–3735. https://doi.org/10.1007/s00330-019-06142-7

    Article  PubMed  Google Scholar 

  29. Xu L, Yang P, Liang W, Liu W, Wang W, Luo C, et al. A radiomics approach based on support vector machine using MR images for preoperative lymph node status evaluation in intrahepatic cholangiocarcinoma. Theranostics. 2019;9(18):5374–5385. https://doi.org/10.7150/thno.34149

    Article  PubMed  PubMed Central  Google Scholar 

  30. Meng ZW, Lin XQ, Zhu JH, Han SH, Chen YL. A nomogram to predict lymph node metastasis before resection in intrahepatic cholangiocarcinoma. J Surg Res. 2018;226:56–63. https://doi.org/10.1016/j.jss.2018.01.024

    Article  PubMed  Google Scholar 

  31. Primrose JN, Fox RP, Palmer DH, Malik HZ, Prasad R, Mirza D, et al. Capecitabine compared with observation in resected biliary tract cancer (BILCAP): a randomised, controlled, multicentre, phase 3 study. Lancet Oncol. 2019;20(5):663–673. https://doi.org/10.1016/S1470-2045(18)30915-X

    Article  CAS  PubMed  Google Scholar 

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Funding

This study was supported by the Research Supporting Program of the Korean Association for the Study of the Liver and the Korean Liver Foundation.

Author information

Author notes

  1. Hyungjin Rhee and Hyun-Ji Lim contributed equally to this work.

Authors and Affiliations

  1. Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, Republic of Korea

    Hyungjin Rhee, Hyun-Ji Lim, Mi-Jung Lee & Mi-Suk Park

  2. Department of Radiology, Research Institute of Radiological Science, Center for Clinical Imaging Data Science, College of Medicine, Yonsei University, Seoul, Korea

    Kyunghwa Han

  3. Department of Radiology, Korea University Ansan Hospital, Korea University College of Medicine, Seoul, Republic of Korea

    Suk-Keu Yeom

  4. Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic‐ro 43‐gil, Songpa‐gu, Seoul, 05505, Republic of Korea

    Sang Hyun Choi & Seung Soo Lee

  5. Department of Radiology, Seoul National University Bundang Hospital, Gyeonggi-Do, Republic of Korea

    Ji Hoon Park

  6. Department of Radiology, Gangnam Severance Hospital, Yonsei University College of Medicine Seoul, Seoul, Republic of Korea

    Eun-Suk Cho

  7. Department of Radiology, National Health Insurance Service Ilsan Hospital, Goyang, Republic of Korea

    Sumi Park

  8. Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea

    Gi Hong Choi & Dai Hoon Han

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  1. Hyungjin Rhee
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Contributions

HR, HJL: conceptualization, data curation, formal analysis, investigation, methodology, writing – original draft, writing – review, and editing. KH, S-KY, SHC, JHP, E-SC, SP, M-JL, GHC, DHH: investigation, writing- review & editing. SSL, M-SP: conceptualization, data curation, formal analysis, funding acquisition, investigation, supervision, writing – original draft, writing – review and editing.

Corresponding authors

Correspondence to Seung Soo Lee or Mi-Suk Park.

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Conflict of interest

Hyungjin Rhee, Hyun‑Ji Lim, Kyunghwa Han, Suk‑Keu Yeom, Sang Hyun Choi, Ji Hoon Park, Eun‑Suk Cho, Sumi Park, Mi‑Jung Lee, Gi Hong Choi, Dai Hoon Han, Seung Soo Lee and Mi‑Suk Park have no relevant financial or non-financial interests to disclose.

Informed consent

This study was conducted in accordance with the ethical guidelines of the Declaration of Helsinki. This retrospective study consisted of a secondary analysis of retrospectively collected multi-institutional (six centers) data that were previously reported [19]. The study was approved by the institutional review board of Severance Hospital (No. 4-2022-0062), and the requirement for written informed consent was waived.

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Rhee, H., Lim, HJ., Han, K. et al. A preoperative scoring system to predict lymph node metastasis in intrahepatic cholangiocarcinoma. Hepatol Int 17, 942–953 (2023). https://doi.org/10.1007/s12072-022-10477-7

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  • DOI: https://doi.org/10.1007/s12072-022-10477-7

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