Prediction Efficacy for Clinical Outcome of Prognostic Nutritional Index in Patients with Resectable Biliary Tract Cancer Depends on Sex and Obstructive Jaundice Status



The Prognostic Nutritional Index (PNI), a marker of nutritional status and systemic inflammation, is a proven prognostic biomarker in some cancers. The predictive value of PNI in biliary tract cancer (BTC) has not been established.


The aim of this study was to determine the relationship between the PNI and outcomes of resectable BTC.


In total, 430 patients with stage I–III resectable BTC [gallbladder cancer (GBC), n = 212; cholangiocarcinoma (CHO), n = 218] who had attended Fudan University Zhongshan Hospital were enrolled. The relationship between the PNI and clinical outcomes was evaluated both in the whole cohort and in selected subgroups.


Eligible patients were classified into PNI-low (PNI < 45) and PNI-high (PNI ≥ 45) groups. The PNI-low group had significantly worse overall survival (OS) in both the whole cohort (p = 0.002) and in the GBC subgroup (p = 0.001), but had similar OS as the PNI-high group in the CHO subgroup (p = 0.328). Multivariate analysis revealed that low PNI is an independent risk factor for worse survival in GBC (hazard ratio 1.623, 95% confidence interval 1.063–2.480, p = 0.026). PNI was found to predict clinical outcome in women (p < 0.001) and patients without obstructive jaundice (p = 0.017) with GBC, but was not a prognostic factor in any subgroup with CHO. The estimated area under the time-dependent receiver operating characteristic curve was significantly greater when TNM stage was combined with PNI in women with GBC.


PNI is an independent predictor of OS in GBC, but not in CHO. It has no prognostic value in men with GBC or patients with obstructive jaundice.

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  1. 1.

    National Comprehensive Cancer Network (NCCN). Clinical practice guidelines in oncology. Hepatobiliary Cancers, Version 2. 2019. Accessed 6 Mar 2019.

  2. 2.

    Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, et al. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66(2):115–32.

    Article  Google Scholar 

  3. 3.

    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69(1):7–34.

    Article  Google Scholar 

  4. 4.

    Misra S, Chaturvedi A, Misra NC, Sharma ID. Carcinoma of the gallbladder. Lancet Oncol. 2003;4(3):167–76.

    Article  Google Scholar 

  5. 5.

    Randi G, Franceschi S, La Vecchia C. Gallbladder cancer worldwide: geographical distribution and risk factors. Int J Cancer. 2006;118(7):1591–602.

    CAS  Article  Google Scholar 

  6. 6.

    Nagorney DM, McPherson GA. Carcinoma of the gallbladder and extrahepatic bile ducts. Semin Oncol. 1988;15(2):106–15.

    CAS  PubMed  Google Scholar 

  7. 7.

    Nervi F, Duarte I, Gomez G, Rodriguez G, Del Pino G, Ferrerio O, et al. Frequency of gallbladder cancer in Chile, a high-risk area. Int J Cancer. 1988;41(5):657–60.

    CAS  Article  Google Scholar 

  8. 8.

    Andrea C, Enzo A. Cholesterol gallstones larger than 3 cm appear to be associated with gallbladder cancer: identification of a high risk group of patients that could benefit from preventive cholecystectomy. Ann Surg. 2016;263(3):e56.

    Article  Google Scholar 

  9. 9.

    Sewnath ME, Karsten TM, Prins MH, Rauws EJ, Obertop H, Gouma DJ. A meta-analysis on the efficacy of preoperative biliary drainage for tumors causing obstructive jaundice. Ann Surg. 2002;236(1):17–27.

    Article  Google Scholar 

  10. 10.

    Kasumova GG, Tabatabaie O, Najarian RM, Callery MP, Ng SC, Bullock AJ, et al. Surgical management of gallbladder cancer: simple versus extended cholecystectomy and the role of adjuvant therapy. Ann Surg. 2017;266(4):625–31.

    Article  Google Scholar 

  11. 11.

    Murakami Y, Uemura K, Sudo T, Hayashidani Y, Hashimoto Y, Nakamura H, et al. Adjuvant gemcitabine plus S-1 chemotherapy improves survival after aggressive surgical resection for advanced biliary carcinoma. Ann Surg. 2009;250(6):950–6.

    Article  Google Scholar 

  12. 12.

    Smale BF, Mullen JL, Buzby GP, Rosato EF. The efficacy of nutritional assessment and support in cancer surgery. Cancer. 1981;47(10):2375–81.

    CAS  Article  Google Scholar 

  13. 13.

    Onodera T, Goseki N, Kosaki G. Prognostic nutritional index in gastrointestinal surgery of malnourished cancer patients [in Japanese]. Nihon Geka Gakkai Zasshi. 1984;85(9):1001–5.

    CAS  PubMed  Google Scholar 

  14. 14.

    Kanda M, Fujii T, Kodera Y, Nagai S, Takeda S, Nakao A. Nutritional predictors of postoperative outcome in pancreatic cancer. Br J Surg. 2011;98(2):268–74.

    CAS  Article  Google Scholar 

  15. 15.

    Pinato DJ, North BV, Sharma R. A novel, externally validated inflammation-based prognostic algorithm in hepatocellular carcinoma: the prognostic nutritional index (PNI). Br J Cancer. 2012;106(8):1439–45.

    CAS  Article  Google Scholar 

  16. 16.

    Jeon HG, Choi DK, Sung HH, Jeong BC, Seo SI, Jeon SS, et al. Preoperative prognostic nutritional index is a significant predictor of survival in renal cell carcinoma patients undergoing nephrectomy. Ann Surg Oncol. 2016;23(1):321–7.

    Article  Google Scholar 

  17. 17.

    Tokunaga R, Sakamoto Y, Nakagawa S, et al. Prognostic nutritional index predicts severe complications, recurrence, and poor prognosis in patients with colorectal cancer undergoing primary tumor resection. Dis Colon Rectum. 2015;58:1048–1057.

    Article  Google Scholar 

  18. 18.

    Okadome K, Baba Y, Yagi T, Kiyozumi Y, Ishimoto T, Iwatsuki M, et al. Prognostic nutritional index, tumor-infiltrating lymphocytes, and prognosis in patients with esophageal cancer. Ann Surg. 2020;271(4):693–700.

    Article  Google Scholar 

  19. 19.

    Dolan RD, McSorley ST, Park JH, Watt DG, Roxburgh CS, Horgan PG, et al. The prognostic value of systemic inflammation in patients undergoing surgery for colon cancer: comparison of composite ratios and cumulative scores. Br J Cancer. 2018;119(1):40–51.

    CAS  Article  Google Scholar 

  20. 20.

    Suzuki Y, Okabayashi K, Hasegawa H, Tsuruta M, Shigeta K, Kondo T, et al. Comparison of preoperative inflammation-based prognostic scores in patients with colorectal cancer. Ann Surg. 2018;267(3):527–31.

    Article  Google Scholar 

  21. 21.

    Baitar A, Kenis C, Decoster L, De Greve J, Lobelle JP, Flamaing J, et al. The prognostic value of 3 commonly measured blood parameters and geriatric assessment to predict overall survival in addition to clinical information in older patients with cancer. Cancer. 2018;124(18):3764–75.

    CAS  Article  Google Scholar 

  22. 22.

    Lin JX, Lin JP, Xie JW, Wang JB, Lu J, Chen QY, et al. Prognostic importance of the preoperative modified systemic inflammation score for patients with gastric cancer. Gastric Cancer. 2019;22(2):403–12.

    CAS  Article  Google Scholar 

  23. 23.

    Ray-Coquard I, Cropet C, Van Glabbeke M, Sebban C, Le Cesne A, Judson I, et al. Lymphopenia as a prognostic factor for overall survival in advanced carcinomas, sarcomas, and lymphomas. Cancer Res. 2009;69(13):5383–91.

    CAS  Article  Google Scholar 

  24. 24.

    Zou W. Immunosuppressive networks in the tumour environment and their therapeutic relevance. Nat Rev Cancer. 2005;5(4):263–74.

    CAS  Article  Google Scholar 

  25. 25.

    Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74.

    CAS  Article  Google Scholar 

  26. 26.

    Wang J, Bo X, Suo T, Liu H, Ni X, Shen S, et al. Tumor-infiltrating neutrophils predict prognosis and adjuvant chemotherapeutic benefit in patients with biliary cancer. Cancer Sci. 2018;109(7):2266–74.

    CAS  Article  Google Scholar 

  27. 27.

    Wang J, Bo X, Wang C, Xin Y, Nan L, Luo R, et al. Low immune index correlates with favorable prognosis but with reduced benefit from chemotherapy in gallbladder cancer. Cancer Sci. 2020;111(1):219–228.

    CAS  Article  Google Scholar 

  28. 28.

    Liu Y, Li P, Lu J, Xiong W, Oger J, Tetzlaff W, et al. Bilirubin possesses powerful immunomodulatory activity and suppresses experimental autoimmune encephalomyelitis. J Immunol. 2008;181(3):1887–97.

    CAS  Article  Google Scholar 

  29. 29.

    Younes RN, Vydelingum NA, Derooij P, Scognamiglio F, Andrade L, Posner MC, et al. Metabolic alterations in obstructive jaundice: effect of duration of jaundice and bile-duct decompression. HPB Surg. 1991;5(1):35–48.

    CAS  Article  Google Scholar 

  30. 30.

    Chang ZK, Kou ZP, Li SX, Lou XL. To evaluate the correlation between the change of immune system function before and after the treatment of malignant obstructive type jaundice treated with biliary stent. Eur Rev Med Pharmacol Sci. 2018;22(6):1638–44.

    PubMed  Google Scholar 

  31. 31.

    Aziz MH, Sideras K, Aziz NA, Mauff K, Haen R, Roos D, et al. The systemic-immune-inflammation index independently predicts survival and recurrence in resectable pancreatic cancer and its prognostic value depends on bilirubin levels: a retrospective multicenter cohort study. Ann Surg. 2019;270(1):139–46.

    Article  Google Scholar 

  32. 32.

    Takahashi Y, Nagino M, Nishio H, Ebata T, Igami T, Nimura Y. Percutaneous transhepatic biliary drainage catheter tract recurrence in cholangiocarcinoma. Br J Surg. 2010;97(12):1860–6.

    CAS  Article  Google Scholar 

  33. 33.

    Wiggers JK, Groot Koerkamp B, Coelen RJ, Doussot A, van Dieren S, Rauws EA, et al. Percutaneous preoperative biliary drainage for resectable perihilar cholangiocarcinoma: no association with survival and no increase in seeding metastases. Ann Surg Oncol. 2015;22 Suppl 3:S1156–63.

    Article  Google Scholar 

  34. 34.

    Singletary BK, Van Thiel DH, Eagon PK. Estrogen and progesterone receptors in human gallbladder. Hepatology. 1986;6(4):574–8.

    Article  Google Scholar 

  35. 35.

    Gabbi C, Kim HJ, Barros R, Korach-Andre M, Warner M, Gustafsson JA. Estrogen-dependent gallbladder carcinogenesis in LXRbeta-/-female mice. Proc Natl Acad Sci USA. 2010;107(33):14763–8.

    CAS  Article  Google Scholar 

  36. 36.

    Gallus S, Negri E, Chatenoud L, Bosetti C, Franceschi S, La Vecchia C. Post-menopausal hormonal therapy and gallbladder cancer risk. Int J Cancer. 2002;99(5):762–3.

    CAS  Article  Google Scholar 

  37. 37.

    Kayahara M, Nagakawa T, Nakagawara H, Kitagawa H, Ohta T. Prognostic factors for gallbladder cancer in Japan. Ann Surg. 2008;248(5):807–14.

    Article  Google Scholar 

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This study was funded by Grants from the National Natural Science Foundation of China (81872352, 81803091), JianFeng Project of XuHui Provincial Commission of Health and Family Planning (SHXH201703) and the Shanghai Medical Discipline of Key Programs for General Surgery (2017ZZ02007) and Clinical Study of Zhongshan Hospital (2018ZSLC24). All study sponsors had no roles in the study design, and in the collection, analysis, and interpretation of data. All authors have contributed significantly to the content of this article.

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Correspondence to Houbao Liu PhD, MD or Yueqi Wang MD.

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Jie Wang, Xiaobo Bo, Min Li, Lingxi Nan, Changcheng Wang, Zhihui Gao, Tao Suo, Xiaoling Ni, Han Liu, Jun Han, Pinxiang Lu, Houbao Liu, and Yueqi Wang declare no potential conflicts of interest.

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Wang, J., Bo, X., Li, M. et al. Prediction Efficacy for Clinical Outcome of Prognostic Nutritional Index in Patients with Resectable Biliary Tract Cancer Depends on Sex and Obstructive Jaundice Status. Ann Surg Oncol (2020).

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