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Prognostic Significance of Tumor Doubling Time in Mass-Forming Type Cholangiocarcinoma

  • Original Article
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Journal of Gastrointestinal Surgery Aims and scope

Abstract

Objective

The aim of this study was to determine the prognostic significance of the preoperatively assessed tumor doubling time (DT) in patients undergoing liver resection for mass-forming intrahepatic cholangiocarcinoma (IHC).

Methods

We evaluated 79 patients who underwent curative resection for IHC, and in whom the same imaging technique was preoperatively available in two consecutive occasions, to allow the calculation of the DT. The influence of DT and other clinical and pathological variables on tumor recurrence and patient survival was determined by the Kaplan–Meier method and uni- and multivariate analysis.

Results

Median overall survival was 40 months; 1-, 3-, and 5-year survival rates were 86.1, 55.1, and 35.1 %, respectively. Median disease-free survival was 17 months; 1-, 3-, and 5-year disease-free survival rates were 62.0, 29.1, and 23.3 %, respectively. At univariate analysis, DT <70 days (p < 0.001) and advanced tumor stage (p = 0.024) were associated with worse overall survival and maintained significance at multivariate analysis.

Conclusions

DT is a clinically useful parameter to estimate the prognosis of “mass-forming” IHC in patients undergoing liver resection.

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References

  1. Edmondson HA, Steiner PE. Primary carcinoma of the liver. A study of 100 cases among 48,900 necropsies. Cancer 1954;7:462–503.

    Article  PubMed  CAS  Google Scholar 

  2. Murakami Y, Uemura K, Sudo T, Hashimoto Y, Nakashima A, Sueda T: Intrahepatic cholangioarcinoma: clinicopathological differences between peripheral type and hilar type. J Gastrointest Surg 2012; 16: 540–548

    Article  PubMed  Google Scholar 

  3. Anderson JE, Hemming AVV, Chang DC, Talamini MA, Mekeel KL (2012) Surgical management trends for cholangiocarcinoma in the USA 1998–2009. J Gastrointest Surg 16(12): 2225–2232.

    Article  PubMed  Google Scholar 

  4. Singal AK, Vauthey JN, Grady JJ, Stroehlein JR. Intra-hepatic cholangiocarcinoma-frequency and demographic patterns: thirty-year data from the M.D. Anderson Cancer Center. J Cancer Res Clin Oncol 2011;137:1071–8.

    Article  PubMed  Google Scholar 

  5. Patel T. Increasing incidence and mortality of primary intrahepatic cholangiocarcinoma in the United States. Hepatology 2001;33:1353–1357.

    Article  PubMed  CAS  Google Scholar 

  6. Farges O, Fuks D, Boleslawski E, Le Treut YP, Castaing D, Laurent A, Ducerf C, Rivoire M, Bachellier P, Chiche L, Nuzzo G, Regimbeau JM: Influence of Surgical Margins on Outcome in Patients With Intrahepatic Cholangiocarcinoma: A Multicenter Study by the AFC-IHCC-2009 Study Group. Ann Surg. 2011;254:824–29.

    Article  PubMed  Google Scholar 

  7. Farges O, Fuks D. Clinical presentation and management of intrahepatic cholangiocarcinoma. Gastroenterol Clin Biol. 2010;34:191–199.

    Article  PubMed  CAS  Google Scholar 

  8. Endo I, Gonen M, Yopp AC, Dalal KM, Zhou Q, Klimstra D, D’Angelica M, DeMatteo RP, Fong Y, Schwartz L, Kemeny N, O’Reilly E, Abou-Alfa GK, Shimada H, Blumgart LH, Jarnagin WR: Intrahepatic cholangiocarcinoma: rising frequency, improved survival, and determinants of outcome after resection. Ann Surg 2008;248:84–96.

    Article  PubMed  Google Scholar 

  9. Guglielmi A, Ruzzenente A, Campagnaro T, Pachera S, Valdegamberi A, Nicoli P, Cappellani A, Malfermoni G, Iacono C: Intrahepatic cholangiocarcinoma: prognostic factors after surgical resection. World J Surg 2009;33: 1247–1254.

    Article  PubMed  Google Scholar 

  10. Shirai K, Ebata T, Oda K, Nishio H, Nagasaka T, Nimura Y, Nagino M: Perineural invasion is a prognostic factor in intrahepatic cholangiocarcinoma. World J Surg 2008;32: 2395–402.

    Article  PubMed  Google Scholar 

  11. Inoue K, Makuuchi M, Takayama T, Torzilli G, Yamamoto J, Shimada K, Kosuge T, Yamasaki S, Konishi M, Kinoshita T, Miyagawa S, Kawasaki S: Long term survival and prognostic factors in the surgical treatment of mass-forming type cholangiocarcinoma. Surgery 2000; 127:498–505.

    Article  PubMed  CAS  Google Scholar 

  12. Saxena A, Chua TC, Sarkar A, Chu F, Morris DL: Clinicopathologic and treatment-related factors influencing recurrence and survival after hepatic resection of intrahepatic cholangiocarcinoma: a 19-year experience from an established Australian hepatobiliary unit. J Gastrointest Surg 2010; 14: 1128–1138

    Article  PubMed  Google Scholar 

  13. Tamandl D, Kaczirek K, Gruenberger B, Koelblinger C, Maresch J, Jakesz R, Gruenberger T: Lymph node ratio after surgery for intrahepatic cholangiocarcinoma. Br J Surg 2009;96:919–925.

    Article  PubMed  CAS  Google Scholar 

  14. Nathan H, Aloia TA, Vauthey JN, Abdalla EK, Zhu AX, Schulick RD, Choti MA, Pawlik TM: Proposed staging system for intrahepatic cholangiocarcinoma. Ann Surg Oncol 2009;16:14–22.

    Article  PubMed  Google Scholar 

  15. Jonas S, Thelen A, Benckert C, Biskup W, Neumann U, Rudolph B, Lopez Haanninen E, Neuhaus P: Extended liver resection for intrahepatic cholangiocarcinoma: a comparison of the prognostic accuracy of the fifth and sixth editions of the TNM classification. Ann Surg 2009; 249: 303–309.

    Article  PubMed  Google Scholar 

  16. Tamandl D, Herberger B, Gruenberger B, Puhalla H, Klinger M, Gruenberger T. Influence of hepatic resection margin on recurrence and survival in intrahepatic cholangiocarcinoma. Ann Surg Oncol 2008;15:2787–94.

    Article  PubMed  Google Scholar 

  17. Collins VP, Loeffler RK, Tivey H. Observation on growth rates of human tumors. Am. J. Roentgenol. 1956;76:988–1000.

    CAS  Google Scholar 

  18. Schwartz M. A biomathematical approach to clinical tumor growth. Cancer 1961;14:1272–1294.

    Article  PubMed  CAS  Google Scholar 

  19. Spratt JS, Meyer JS, Spratt JA: Rates of growth of human neoplasms: part II. J Surg Oncol 1996;61:68–83.

    Article  PubMed  CAS  Google Scholar 

  20. Cucchetti A, Vivarelli M, Piscaglia F, Nardo B, Montalti R, Grazi GL, Ravaioli M, La Barba G, Cavallari A, Bolondi L, Pinna AD: Tumor doubling time predicts recurrence after surgery and describes the histological pattern of hepatocellular carcinoma on cirrhosis. J Hepatol 2005; 43: 310–316.

    Article  PubMed  Google Scholar 

  21. Strasberg SM, Belghiti J, Clavien PA, Gadzijev E, Garden JO, Lau WY, Makuuchi M: The Brisbane 2000 terminology of liver anatomy and resections. HPB 2000 ; 2 : 333–9

    Google Scholar 

  22. Nuzzo G, Giuliante F, Ardito F, De Rose AM, Vellone M, Clemente G, Chiarla C, Giovannini I: Intrahepatic cholangiocarcinoma: prognostic factors after liver resection. Updates Surg 2010;62:11–9.

    Article  PubMed  Google Scholar 

  23. Ercolani G, Vetrone G, Grazi GL, Aramaki O, Cescon M, Ravaioli M, Serra C, Brandi G, Pinna AD: Intrahepatic cholangiocarcinoma. Primary Liver resection and aggressive multimodal treatment of recurrence significantly prolong survival. Ann Surg 2010; 252: 107–114.

    Article  PubMed  Google Scholar 

  24. Edge SB, Byrd DR, Carducci MA, Compton CC (2009) eds. AJCC Cancer Staging Manual. 7th ed. New York: Springer

    Google Scholar 

  25. Sobin LH, Wittekind C (eds) (2002). TNM classification of malignant tumours, 6th ed. Wiley: New York.

    Google Scholar 

  26. Wang N-P, Zee S, Zarbo RJ, Bacchi CE, Gown AM. Coordinate expression of cytokeratins 7 and 20 defines unique subsets of carcinomas. Appl Immunohistochem 1995;3:99–107.

    Google Scholar 

  27. Maeda T, Kajiyama K, Adachi E, Takenaka K, Sugimachi K, Tsuneyoshi M: The expression of cytokeratins 7, 19, and 20 in primary and metastatic carcinomas of the liver. Mod Pathol 1996;9:901–9.

    PubMed  CAS  Google Scholar 

  28. Zhou HB, Wang H, Li YQ, Li SX, Wang H, Zhou DX, Tu QQ, Wang Q, Zou SS, Wu MC, Hu HP: Hepatitis B virus infection: a favorable prognostic factor for intrahepatic cholangiocarcinoma after resection. World J Gastroenterol 2011; 17: 1292–303.

    Article  PubMed  Google Scholar 

  29. Li YY, Li H, Lv P Liu G, Li XR, Tian BN, Chen DJ: Prognostic value of cirrhosis for intrahepatic cholangiocarcinoma after surgical treatment. J Gastrointest Surg 2011; 15: 608–613

    Article  PubMed  Google Scholar 

  30. Guedj N, Zhan Q, Perigny M, Rautou PE, Degos F, Belghiti J, Farges O, Bedossa P, Paradis V: Comparative protein expression profiles of hilar and peripheral hepatic cholangiocarcinomas J Hepatol 2009;51: 93–101.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

Supported by a contribution of the Catholic University and the Italian Ministry for Instruction, University and Research (D.1 Funds)

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Authors and Affiliations

  1. Department of Surgical Sciences, Hepatobiliary Unit, Agostino Gemelli Hospital, School of Medicine, Catholic University of Sacred Heart, Largo Gemelli 8, 00168, Rome, Italy

    Agostino Maria De Rose, Gennaro Clemente, Francesco Ardito, Ivo Giovannini, Felice Giuliante & Gennaro Nuzzo

  2. Department of Surgery and Transplantation, Liver and Multiorgan Transplant Unit, Sant’Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy

    Alessandro Cucchetti, Giorgio Ercolani & Antonio Daniele Pinna

Authors
  1. Agostino Maria De Rose
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  2. Alessandro Cucchetti
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  3. Gennaro Clemente
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  4. Francesco Ardito
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  5. Ivo Giovannini
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  6. Giorgio Ercolani
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  7. Felice Giuliante
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  8. Antonio Daniele Pinna
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  9. Gennaro Nuzzo
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Correspondence to Gennaro Clemente.

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De Rose, A.M., Cucchetti, A., Clemente, G. et al. Prognostic Significance of Tumor Doubling Time in Mass-Forming Type Cholangiocarcinoma. J Gastrointest Surg 17, 739–747 (2013). https://doi.org/10.1007/s11605-012-2129-6

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  • DOI: https://doi.org/10.1007/s11605-012-2129-6

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