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Predictors of postoperative early recurrence of extrahepatic bile duct cancer

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Abstract

Purposes

Resected bile duct cancers often relapse during postoperative follow-up. The aim of this study was to detect predictors of early recurrence in patients with extrahepatic bile duct cancer.

Methods

Consecutive cases (n = 162) of extrahepatic bile duct cancer in which R0 or R1 resection was achieved in Kobe University Hospital between 2000 and 2016 were divided into three groups [early recurrence (ER), within 6 months of surgery, late recurrence (LR), and no recurrence (NR)] and their clinicopathological features were compared.

Results

Twenty-two patients (14%) developed ER and 69 (43%) developed LR after surgery. The rates of lymph node metastasis and residual cancer status were similar in all three groups. Liver metastasis was more common in the ER group than in the LR group (59% vs. 32%, p = 0.02). ER had a significantly worse prognosis than LR and NR (7% vs. 44% vs. 85% at 1 year, p < 0.01, respectively). Multivariate analysis showed that age > 75 years, serum CA19-9 > 1008 U/ml and perineural invasion were independent predictors of early recurrence.

Conclusions

High serum CA19-9 values (> 1008 U/ml) were an independent predictor of early recurrence. Neoadjuvant therapy and aggressive adjuvant therapy may be beneficial for patients who show highly elevated CA19-9 values before surgery.

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References

  1. Sugiura T, Uesaka K, Kanemoto H, Mizuno T, Sasaki K, Furukawa H, et al. Serum CA19-9 is a significant predictor among preoperative parameters for early recurrence after resection of pancreatic adenocarcinoma. J Gastrointest Surg. 2012;16:977–85.

    Article  Google Scholar 

  2. La Torre M, Nigri G, Lo Conte A, Mazzuca F, Tierno SM, Salaj A, et al. Is a preoperative assessment of the early recurrence of pancreatic cancer possible after complete surgical resection? Gut Liver. 2014;8:102–8.

    Article  Google Scholar 

  3. Groot VP, Gemenetzis G, Blair AB, Rivero-Soto RJ, Yu J, Javed AA, et al. Defining and predicting early recurrence in 957 patients with resected pancreatic ductal adenocarcinoma. Ann Surg. 2018. https://doi.org/10.1097/SLA.0000000000002734.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Fouquet T, Germain A, Brunaud L, Bresler L, Ayav A. Is perineural invasion more accurate than other factors to predict early recurrence after pancreatoduodenectomy for pancreatic head adenocarcinoma? World J Surg. 2014;38:2132–7.

    Article  Google Scholar 

  5. Matsumoto I, Murakami Y, Shinzeki M, Asari S, Goto T, Tani M, et al. Proposed preoperative risk factors for early recurrence in patients with resectable pancreatic ductal adenocarcinoma after surgical resection: a multi-center retrospective study. Pancreatology. 2015;15:674–80.

    Article  Google Scholar 

  6. Akita M, Ajiki T, Matsumoto T, Shinozaki K, Goto T, Asari S, et al. Preoperative cholangitis affects survival outcome in patients with extrahepatic bile duct cancer. J Gastrointest Surg. 2017;21:983–9.

    Article  Google Scholar 

  7. Kato Y, Takahashi S, Gotohda N, Konishi M. Prognostic impact of the initial postoperative CA19-9 level in patients with extrahepatic bile duct cancer. J Gastrointest Surg. 2016;20:1435–43.

    Article  Google Scholar 

  8. Hu HJ, Mao H, Shrestha A, Tan YQ, Ma WJ, Yang Q, et al. Prognostic factors and long-term outcomes of hilar cholangiocarcinoma: a single-institution experience in China. World J Gastroenterol. 2016;22:2601–10.

    Article  CAS  Google Scholar 

  9. Wellner UF, Shen Y, Keck T, Jin W, Xu Z. The survival outcome and prognostic factors for distal cholangiocarcinoma following surgical resection: a meta-analysis for the 5-year survival. Surg Today. 2017;47:271–9.

    Article  CAS  Google Scholar 

  10. Ito Y, Abe Y, Egawa T, Kitago M, Itano O, Kitagawa Y. Predictive factors of early recurrence in patients with distal cholangiocarcinoma after pancreaticoduodenectomy. Gastroenterol Res Pract. 2018. https://doi.org/10.1155/2018/6431254.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Wang JK, Hu HJ, Shrestha A, Ma WJ, Yang Q, Liu F, et al. Can preoperative and postoperative CA19-9 levels predict survival and early recurrence in patients with resectable hilar cholangiocarcinoma? Oncotarget. 2017;8:45335–44.

    PubMed  PubMed Central  Google Scholar 

  12. Lee HS, Lee SH, Roh YH, Chung MJ, Park JY, Park SW, et al. Efficacy of adjuvant chemotherapy and prognostic factors for patients with extrahepatic bile duct cancer. Chemotherapy. 2016;61:152–8.

    Article  Google Scholar 

  13. Okabayashi T, Shima Y, Iwata J, Morita S, Sumiyoshi T, Sui K, et al. Characterization of prognostic factors and the efficacy of adjuvant s-1 chemotherapy in patients with post-surgery extrahepatic bile duct cancer. Anticancer Res. 2017;37:7049–56.

    PubMed  Google Scholar 

  14. Edge SB. American Joint Committee on Cancer AJCC Cancer staging manual. 7th ed. New York: Springer; 2009.

    Google Scholar 

  15. Kim BH, Kim E, Kim K, Jang JY, Kim SW, Oh DY, et al. The impact of perioperative CA19-9 change on the survival and recurrence patterns after adjuvant chemoradiotherapy in resectable extrahepatic cholangiocarcinoma. J Surg Oncol. 2018;117:380–8.

    Article  CAS  Google Scholar 

  16. Honda K, Katzke VA, Hüsing A, Okaya S, Shoji H, Onidani K, et al. CA19-9 and apolipoprotein-A2 isoforms as detection markers for pancreatic cancer: a prospective evaluation. Int J Cancer. 2019;144:1877–87.

    Article  CAS  Google Scholar 

  17. Shang X, Song C, Du X, Shao H, Xu D, Wang X. The serum levels of tumor marker CA19-9, CEA, CA72-4, and NSE in type 2 diabetes without malignancy and the relations to the metabolic control. Saudi Med J. 2017;38:204–8.

    Article  Google Scholar 

  18. Bertino G, Ardiri AM, Boemi P, Bruno CM, Valenti M, Mazzarino MC, et al. Meaning of elevated CA 19-9 serum levels in chronic hepatitis and HCV-related cirrhosis. Minerva Gastroenterol Dietol. 2007;53:305–9.

    CAS  PubMed  Google Scholar 

  19. Albert MB, Steinberg WM, Henry JP. Elevated serum levels of tumor marker CA19-9 in acute cholangitis. Dig Dis Sci. 1988;33:1223–5.

    Article  CAS  Google Scholar 

  20. Rieser CJ, Zenati M, Hamad A, Al Abbas AI, Bahary N, Zureikat AH, et al. CA19-9 on postoperative surveillance in pancreatic ductal adenocarcinoma: predicting recurrence and changing prognosis over time. Ann Surg Oncol. 2018;25:3483–91.

    Article  Google Scholar 

  21. Kondo N, Murakami Y, Uemura K, Sudo T, Hashimoto Y, Sasaki H, et al. Elevated perioperative serum CA 19-9 levels are independent predictors of poor survival in patients with resectable cholangiocarcinoma. J Surg Oncol. 2014;110:422–9.

    Article  CAS  Google Scholar 

  22. Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, ABC-02 Trial Investigators, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010;362:1273–81.

    Article  CAS  Google Scholar 

  23. Kato A, Shimizu H, Ohtsuka M, Yoshidome H, Yoshitomi H, Furukawa K, et al. Surgical resection after downsizing chemotherapy for initially unresectable locally advanced biliary tract cancer: a retrospective single-center study. Ann Surg Oncol. 2013;20:318–24.

    Article  Google Scholar 

  24. Grendar J, Grendarova P, Sinha R, Dixon E. Neoadjuvant therapy for downstaging of locally advanced hilar cholangiocarcinoma: a systematic review. HPB (Oxford). 2014;16:297–303.

    Article  Google Scholar 

  25. Le Roy B, Gelli M, Pittau G, Allard MA, Pereira B, Serji B, et al. Neoadjuvant chemotherapy for initially unresectable intrahepatic cholangiocarcinoma. Br J Surg. 2018;105:839–47.

    Article  Google Scholar 

  26. Buettner S, Koerkamp BG, Ejaz A, Buisman FE, Kim Y, Margonis GA, et al. The effect of preoperative chemotherapy treatment in surgically treated intrahepatic cholangiocarcinoma patients-A multi-institutional analysis. J Surg Oncol. 2017;115:312–8.

    Article  CAS  Google Scholar 

  27. Ebata T, Hirano S, Konishi M, Uesaka K, Tsuchiya Y, Ohtsuka M, Bile Duct Cancer Adjuvant Trial (BCAT) Study Group, et al. Randomized clinical trial of adjuvant gemcitabine chemotherapy versus observation in resected bile duct cancer. Br J Surg. 2018;105:192–202.

    Article  CAS  Google Scholar 

  28. Kobayashi S, Nagano H, Tomokuni A, Gotoh K, Sakai D, Hatano E, et al. Kansai Hepato-Biliary Oncology (KHBO) Group A prospective, randomized phase II study of adjuvant gemcitabine versus S-1 after major hepatectomy for biliary tract cancer (KHBO 1208): Kansai Hepato-Biliary Oncology Group. Ann Surg. 2019;270:230–7.

    Article  Google Scholar 

  29. Okusaka T, Nakachi K, Fukutomi A, Mizuno N, Ohkawa S, Funakoshi A, et al. Gemcitabine alone or in combination with cisplatin in patients with biliary tract cancer: a comparative multicentre study in Japan. Br J Cancer. 2010;103:469–74.

    Article  CAS  Google Scholar 

  30. Buettner S, Spolverato G, Kimbrough CW, Alexandrescu S, Marques HP, Lamelas J, et al. The impact of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio among patients with intrahepatic cholangiocarcinoma. Surgery. 2018;164:411–8.

    Article  Google Scholar 

  31. Kitano Y, Yamashita YI, Yamamura K, Arima K, Kaida T, Miyata T, et al. Effects of preoperative neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios on survival in patients with extrahepatic cholangiocarcinoma. Anticancer Res. 2017;37:3229–377.

    CAS  PubMed  Google Scholar 

  32. Cui P, Pang Q, Wang Y, Qian Z, Hu X, Wang W, et al. Nutritional prognostic scores in patients with hilar cholangiocarcinoma treated by percutaneous transhepatic biliary stenting combined with 125I seed intracavitary irradiation: a retrospective observational study. Medicine (Baltimore). 2018;97:e11000.

    Article  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, 650-0017, Japan

    Masayuki Akita, Tetsuo Ajiki, Kimihiko Ueno, Daisuke Tsugawa, Yu Hashimoto, Motofumi Tanaka, Masahiro Kido, Hirochika Toyama & Takumi Fukumoto

Authors
  1. Masayuki Akita
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  2. Tetsuo Ajiki
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  3. Kimihiko Ueno
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  4. Daisuke Tsugawa
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  5. Yu Hashimoto
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  6. Motofumi Tanaka
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  7. Masahiro Kido
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  8. Hirochika Toyama
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  9. Takumi Fukumoto
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Contributions

MA: study design and interpretation of data; and drafting of the manuscript. KU, DT, YH, MT, MK, HT, and TF: analysis of clinical data; drafting of the manuscript; and interpretation of data. TA; drafting of the manuscript; and study supervision.

Corresponding author

Correspondence to Tetsuo Ajiki.

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The authors declare no conflicts of interest in association with the present study.

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Akita, M., Ajiki, T., Ueno, K. et al. Predictors of postoperative early recurrence of extrahepatic bile duct cancer. Surg Today 50, 344–351 (2020). https://doi.org/10.1007/s00595-019-01880-z

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  • DOI: https://doi.org/10.1007/s00595-019-01880-z

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