Skip to main content

Comparison of Prognostic Value of Red Cell-Related Parameters of Biliary Tract Cancer After Surgical Resection and Integration of a Prognostic Nomogram: A Retrospective Study

Advances in Therapy volume 38, pages 1227–1244 (2021)Cite this article

Abstract

Introduction

Biliary tract cancer (BTC) comprises infrequently occurring neoplasms with poor prognoses. Red blood cell-related parameters are commonly reported prognostic factors. We aimed to compare and evaluate the clinical value of red blood cell-related parameters and develop a prognostic nomogram.

Methods

The analysis involved 418 patients with BTC who underwent surgery from December 2003 to April 2017. Patients were divided into training and validation cohorts. Red blood cell-related parameters were compared using Kaplan-Meier analysis, the area under receiver-operating characteristic curve (AUC), and C-index. Predictive abilities were evaluated using Cox regression. We developed a nomogram incorporating superior parameters verified using calibration curves, internal validation, and subgroup analysis. The nomogram was compared with the tumour-node-metastasis staging system through ROC, C-index, and Kaplan-Meier analysis.

Results

A combined parameter comprising haemoglobin, albumin, lymphocytes, and platelets (HALP), which was superior to other red blood cell-related parameters, indicated a high risk of worse overall survival when low. Univariate analysis revealed that HALP together with other clinical characteristics was associated with overall survival. Multivariate analysis revealed that HALP, tumour-node-metastasis staging, and operative outcome were independent predictors of poor overall survival. Internal validation proved the predictive value of the nomogram. Additional statistical analyses established the advantages of the nomogram vs. tumour-node-metastasis staging.

Conclusion

HALP was a superior red blood cell-related parameter and an independent predictor of prognosis. Our nomogram based on HALP, tumour-node-metastasis staging, and operative outcome is a promising model for predicting overall survival.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

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

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

References

  1. Razumilava N, Gores GJ. Cholangiocarcinoma. Lancet. 2014;383(9935):2168–79.

    Article  Google Scholar 

  2. Patel T. Cholangiocarcinoma–controversies and challenges. Nat Rev Gastroenterol Hepatol. 2011;8(4):189–200.

    CAS  Article  Google Scholar 

  3. Perinel J, Adham M. Preoperative biliary drainage for resectable or borderline resectable periampullary tumor: what is the best management? Hepatob Surg Nutr. 2019;8(4):398–400.

    Article  Google Scholar 

  4. Xue L, Guo C, Zhang K, Jiang H, Pang F, Dou Y, et al. Comprehensive molecular profiling of extrahepatic cholangiocarcinoma in Chinese population and potential targets for clinical practice. Hepatob Surg Nutr. 2019;8(6):615–22.

    Article  Google Scholar 

  5. Lepage C, Cottet V, Chauvenet M, Phelip JM, Bedenne L, Faivre J, et al. Trends in the incidence and management of biliary tract cancer: a French population-based study. J Hepatol. 2011;54(2):306–10.

    Article  Google Scholar 

  6. Jarnagin WR, Fong Y, DeMatteo RP, Gonen M, Burke EC, Bodniewicz J, et al. Staging, resectability, and outcome in 225 patients with hilar cholangiocarcinoma. Ann Surg. 2001;234(5):507–19.

    CAS  Article  Google Scholar 

  7. Zhang XF, Beal EW, Bagante F, Chakedis J, Weiss M, Popescu I, et al. Early versus late recurrence of intrahepatic cholangiocarcinoma after resection with curative intent. Br J Surg. 2018;105(7):848–56.

    Article  Google Scholar 

  8. Ma WJ, Wu ZR, Shrestha A, Yang Q, Hu HJ, Wang JK, et al. Effectiveness of additional resection of the invasive cancer-positive proximal bile duct margin in cases of hilar cholangiocarcinoma. Hepatob Surg Nutr. 2018;7(4):251–69.

    Article  Google Scholar 

  9. Amin MB, Greene FL, Edge SB, Compton CC, Gershenwald JE, Brookland RK, et al. The eighth edition AJCC cancer staging manual: continuing to build a bridge from a population-based to a more "personalized" approach to cancer staging. CA Cancer J Clin. 2017;67(2):93–9.

  10. Tang LQ, Li CF, Li J, Chen WH, Chen QY, Yuan LX, et al. Establishment and validation of prognostic nomograms for endemic nasopharyngeal carcinoma. J Natl Cancer Inst. 2016;108(1).

  11. Ficarra V, Galfano A, Novara G, Iafrate M, Brunelli M, Secco S, et al. Risk stratification and prognostication of renal cell carcinoma. World J Urol. 2008;26(2):115–25.

    Article  Google Scholar 

  12. Yoshida N, Kosumi K, Tokunaga R, Baba Y, Nagai Y, Miyamoto Y, et al. Clinical importance of mean corpuscular volume as a prognostic marker after esophagectomy for esophageal cancer. Ann Surg. 2020;271(3):494–501.

    Article  Google Scholar 

  13. Zhang X, Zhang F, Qiao W, Zhang X, Zhao Z, Li M. Low hematocrit is a strong predictor of poor prognosis in lung cancer patients. Biomed Res Int. 2018;2018:6804938.

    PubMed  PubMed Central  Google Scholar 

  14. Koma Y, Onishi A, Matsuoka H, Oda N, Yokota N, Matsumoto Y, et al. Increased red blood cell distribution width associates with cancer stage and prognosis in patients with lung cancer. PLoS One. 2013;8(11):e80240.

    CAS  Article  Google Scholar 

  15. Xu SS, Li S, Xu HX, Li H, Wu CT, Wang WQ, et al. Haemoglobin, albumin, lymphocyte and platelet predicts postoperative survival in pancreatic cancer. World J Gastroenterol. 2020;26(8):828–38.

    CAS  Article  Google Scholar 

  16. Bozkaya Y, Kurt B, Gurler F. A prognostic parameter in advanced non-small cell lung cancer: the ratio of hemoglobin-to-red cell distribution width. Int J Clin Oncol. 2019;24(7):798–806.

    CAS  Article  Google Scholar 

  17. J. B, A. L, H. W. Prognostic factors for progression-free and overall survival in advanced biliary tract cancer. Ann Oncol. 2015.

  18. Association WM. World medical association declaration of helsinki: ethical principles for medical research involving human subjects. JAMA. 2013;310(20):2191–4.

    Article  Google Scholar 

  19. Peng D, Zhang CJ, Gong YQ, Hao H, Guan B, Li XS, et al. Prognostic significance of HALP (hemoglobin, albumin, lymphocyte and platelet) in patients with bladder cancer after radical cystectomy. Sci Rep. 2018;8(1):794.

    Article  Google Scholar 

  20. Li J, Chen S, Peng S, Liu Y, Xing S, He X, et al. Prognostic nomogram for patients with Nasopharyngeal Carcinoma incorporating hematological biomarkers and clinical characteristics. Int J Biol Sci. 2018;14(5):549–56.

    CAS  Article  Google Scholar 

  21. Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, et al. Phase 3 trial of everolimus for metastatic renal cell carcinoma: final results and analysis of prognostic factors. Cancer. 2010;116(18):4256–65.

    CAS  Article  Google Scholar 

  22. Chakedis J, Spolverato G, Beal EW, Woelfel I, Bagante F, Merath K, et al. Pre-operative sarcopenia identifies patients at risk for poor survival after resection of biliary tract cancers. J Gastrointest Surg. 2018;22(10):1697–708.

    Article  Google Scholar 

  23. Jansson H, Cornillet M, Bjorkstrom NK, Sturesson C, Sparrelid E. Prognostic value of preoperative inflammatory markers in resectable biliary tract cancer—validation and comparison of the Glasgow Prognostic Score and Modified Glasgow Prognostic Score in a Western cohort. Eur J Surg Oncol. 2020;46(5):804–10.

    Article  Google Scholar 

  24. Cho K-M, Han S-W, Park H, Im S-A, Oh D-Y, Kim T-Y, et al. Neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and their dynamic changes during chemotherapy is useful to predict a more accurate prognosis of advanced biliary tract cancer. Oncotarget. 2016;8(2):2329–41

  25. Nakashima S, Kobayashi S, Nagano H, Tomokuni A, Tomimaru Y, Asaoka T, et al. BRCA/Fanconi anemia pathway implicates chemoresistance to gemcitabine in biliary tract cancer. Cancer Sci. 2015;106(5):584–91.

    CAS  Article  Google Scholar 

  26. Alvaro Sanz E, Garrido Siles M, Rey Fernandez L, Villatoro Roldan R, Rueda Dominguez A, Abiles J. Nutritional risk and malnutrition rates at diagnosis of cancer in patients treated in outpatient settings: early intervention protocol. Nutrition. 2019;57:148–53.

    Article  Google Scholar 

  27. Yang X-w, Yuan J-m, Chen J-y, Yang J, Gao Q-g, Yan X-z, et al. The prognostic importance of jaundice in surgical resection with curative intent for gallbladder cancer. BMC Cancer. 2014;14.

Download references

Acknowledgements

We thank the participants of the study.

Funding

This work was supported by grants from CAMS Innovation Fund for Medical Sciences (CIFMS) (no. 2016-I2M-1–001), the Fundamental Research Funds for the Central Universities (3332020085), and Tsinghua University-Peking Union Medical College Hospital Cooperation Project (PTQH201904552). The journal’s rapid service fee was paid for by the authors.

Editorial Assistance

We thank Liwen Bianji, Edanz Editing China (www.liwenbianji.cn/ac), for editing the English text of a draft of this manuscript. This was funded by the corresponding author’s department.

Authorship

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Authorship Contributions

Conceptualization, L.S., A.G., Y.J., H.Y. and Y.M.; methodology, M.L, Y.X., H.X., S.D., H.Z., X.L., X.S., S.Z.; software, A.G..; validation, Y.M.; formal analysis, L.S., A.G.; writing-original draft preparation, L.S., A.G.; writing-review and editing, L.S.; supervision, Y.M.

Disclosures

L.S., A.G., Y.J., M.L., Y.X., H.X., S.D., H.Z., X.L., X.S., S.Z., H.Y., and Y.M. have nothing to disclose.

Compliance with Ethics Guidelines

The Medical Ethics Committees of Peking Union Medical College Hospital of the Chinese Academy of Medical Sciences and Peking Union Medical College approved the study, which was conducted in accordance with the ethical standards of the World Medical Association’s Declaration of Helsinki [18]. The requirement for informed consent was waived because this was a retrospective study.

Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Author information

Author notes

  1. These authors Lejia Sun, Ai Guan, and Yukai Jin contributed equally to this article.

Authors and Affiliations

  1. Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC and Chinese Academy of Medical Sciences, Beijing, China

    Lejia Sun, Yukai Jin, Yao Xiao, Haifeng Xu, Shunda Du, Haitao Zhao, Xin Lu, Xinting Sang, Shouxian Zhong, Huayu Yang & Yilei Mao

  2. Peking Union Medical College (PUMC), PUMC and Chinese Academy of Medical Sciences, Beijing, China

    Ai Guan & Meixi Liu

Authors
  1. Lejia Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ai Guan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yukai Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Meixi Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yao Xiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Haifeng Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shunda Du
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Haitao Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Xin Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Xinting Sang
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Shouxian Zhong
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Huayu Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Yilei Mao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Huayu Yang or Yilei Mao.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (docx 1672 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Sun, L., Guan, A., Jin, Y. et al. Comparison of Prognostic Value of Red Cell-Related Parameters of Biliary Tract Cancer After Surgical Resection and Integration of a Prognostic Nomogram: A Retrospective Study. Adv Ther 38, 1227–1244 (2021). https://doi.org/10.1007/s12325-020-01595-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12325-020-01595-5

Keywords

  • Biliary tract cancer
  • HALP
  • Nomogram
  • Prognosis