Recurrence after operative management of intrahepatic cholangiocarcinoma

Omar Hyder, Ioannis Hatzaras, Georgios C Sotiropoulos, Andreas Paul, Sorin Alexandrescu, Hugo Marques, Carlo Pulitano, Eduardo Barroso, Bryan M Clary, Luca Aldrighetti, Cristina R Ferrone, Andrew X Zhu, Todd W Bauer, Dustin M Walters, Ryan Groeschl, T Clark Gamblin, J Wallis Marsh, Kevin T Nguyen, Ryan Turley, Irinel Popescu, Catherine Hubert, Stephanie Meyer, Michael A Choti, Jean-Francois Gigot, Gilles Mentha, Timothy M Pawlik, Omar Hyder, Ioannis Hatzaras, Georgios C Sotiropoulos, Andreas Paul, Sorin Alexandrescu, Hugo Marques, Carlo Pulitano, Eduardo Barroso, Bryan M Clary, Luca Aldrighetti, Cristina R Ferrone, Andrew X Zhu, Todd W Bauer, Dustin M Walters, Ryan Groeschl, T Clark Gamblin, J Wallis Marsh, Kevin T Nguyen, Ryan Turley, Irinel Popescu, Catherine Hubert, Stephanie Meyer, Michael A Choti, Jean-Francois Gigot, Gilles Mentha, Timothy M Pawlik

Abstract

Introduction: Data on recurrence after operation for intrahepatic cholangiocarcinoma (ICC) are limited. We sought to investigate rates and patterns of recurrence in patients after operative intervention for ICC.

Methods: We identified 301 patients who underwent operation for ICC between 1990 and 2011 from an international, multi-institutional database. Clinicopathologic data, recurrence patterns, and recurrence-free survival (RFS) were analyzed.

Results: During the median follow up duration of 31 months (range 1-208), 53.5% developed a recurrence. Median RFS was 20.2 months and 5-year actuarial disease-free survival, 32.1%. The most common site for initial recurrence after operation of ICC was intrahepatic (n = 98; 60.9%), followed by simultaneous intra- and extrahepatic disease (n = 30; 18.6%); 33 (21.0%) patients developed extrahepatic recurrence only as the first site of recurrence. Macrovascular invasion (hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.34-3.21; P < .001), nodal metastasis (HR, 1.55; 95% CI, 1.01-2.45; P = .04), unknown nodal status (HR, 1.57; 95% CI, 1.10-2.25; P = .04), and tumor size ≥ 5 cm (HR, 1.84; 95% CI, 1.28-2.65; P < .001) were independently associated with increased risk of recurrence. Patients were assigned a clinical score from 0 to 3 according to the presence of these risk factors. The 5-year RFS for patients with scores of 0, 1, 2, and 3 was 61.8%, 36.2%, 19.5%, and 9.6%, respectively.

Conclusion: Recurrence after operative intervention for ICC was common. Disease recurred both at intra- and extrahepatic sites with roughly the same frequency. Factors such as lymph node metastasis, tumor size, and vascular invasion predict highest risk of recurrence.

Copyright © 2013 Mosby, Inc. All rights reserved.

Figures

Fig 1
Fig 1
Median RFS was 20.2 months (95% CI, 16.4–28.0). Overall 1-, 3-, and 5-year actuarial RFS was 64.2%, 39.0%, and 32.1%, respectively. (Color version of figure is available online.)
Fig 2
Fig 2
Tumor size and nodal status adversely affected the RFS. A, Patients with tumor size ≥5 cm had a worse RFS than those with smaller tumors. B, Patients with N0 disease also had a longer RFS than those with N1 and Nx disease. (Color version of figure is available online.)
Fig 3
Fig 3
Vascular and perineural invasion both predicted poor survival. A, Patients with no vascular invasion, macroscopic, and microscopic invasion had a median RFS of 28.0, 9.6, and 18.1 months, respectively. B, Patients with perineural invasion had a median survival of 11.4 months compared with 21.8 months for patients without such invasion. (Color version of figure is available online.)
Fig 4
Fig 4
RFS declined with an increasing clinical score. The 5-year RFS for patients with scores 0, 1, 2, and 3 was 61.8%, 36.2%, 19.5%, and 9.6%, respectively. (Color version of figure is available online.)

References

    1. Kaczynski J, Hansson G, Wallerstedt S. Incidence, etiologic aspects and clinicopathologic features in intrahepatic cholangiocellular carcinoma—a study of 51 cases from a low-endemicity area. Acta Oncol. 1998;37:77–83.
    1. Shaib Y, El-Serag HB. The epidemiology of cholangiocarcinoma. Semin Liver Dis. 2004;24:115–25.
    1. Benson AB, 3rd, Abrams TA, Ben-Josef E, et al. NCCN clinical practice guidelines in oncology: hepatobiliary cancers. J Natl Comprehensive Cancer Network. 2009;7:350–91.
    1. de Jong MC, Nathan H, Sotiropoulos GC, et al. Intrahepatic cholangiocarcinoma: an international multi-institutional analysis of prognostic factors and lymph node assessment. J Clin Oncol. 2011;29:3140–5.
    1. Nuzzo G, Giuliante F, Ardito F, et al. Intrahepatic cholangiocarcinoma: prognostic factors after liver resection. Updates Surg. 2010;62:11–9.
    1. Isaji S, Kawarada Y, Taoka H, et al. Clinicopathological features and outcome of hepatic resection for intrahepatic cholangiocarcinoma in Japan. J Hepatobil Pancreatic Sur. 1999;6:108–16.
    1. Nakagohri T, Asano T, Kinoshita H, et al. Aggressive surgical resection for hilar-invasive and peripheral intrahepatic cholangiocarcinoma. World J Surg. 2003;27:289–93.
    1. Nathan H, Pawlik TM, Wolfgang CL, et al. Trends in survival after surgery for cholangiocarcinoma: a 30-year population-based SEER database analysis. J Gastrointest Surg. 2007;11:1488–96.
    1. Guglielmi A, Ruzzenente A, Campagnaro T, et al. Intrahepatic cholangiocarcinoma: prognostic factors after surgical resection. World J Surg. 2009;33:1247–54.
    1. Lang H, Sotiropoulos GC, Sgourakis G, et al. Operations for intrahepatic cholangiocarcinoma: single-institution experience of 158 patients. J Am Coll Surg. 2009;208:218–28.
    1. Nathan H, Aloia TA, Vauthey JN, et al. A proposed staging system for intrahepatic cholangiocarcinoma. Ann Surg Oncol. 2009;16:14–22.
    1. Hatzaras I, Schmidt C, Muscarella P, et al. Elevated CA 19-9 portends poor prognosis in patients undergoing resection of biliary malignancies. HPB. 2010;12:134–8.
    1. Nathan H, Pawlik TM. Staging of intrahepatic cholangiocarcinoma. Curr Opin Gastroenterol. 2010;26:269–73.
    1. Murakami Y, Uemura K, Sudo T, et al. Prognostic factors after surgical resection for intrahepatic, hilar, and distal cholangiocarcinoma. Ann Surg Oncol. 2011;18:651–8.
    1. Poultsides GA, Zhu AX, Choti MA, Pawlik TM. Intrahepatic cholangiocarcinoma. Surg Clin North Am. 2010;90:817–37.
    1. Valle J, Wasan H, Palmer DH, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010;362:1273–81.
    1. Hong K, Geschwind JF. Locoregional intra-arterial therapies for unresectable intrahepatic cholangiocarcinoma. Semin Oncol. 2010;37:110–7.
    1. Zeng ZC, Tang ZY, Fan J, et al. Consideration of the role of radiotherapy for unresectable intrahepatic cholangiocarcinoma: a retrospective analysis of 75 patients. Cancer J. 2006;12:113–22.
    1. Chen LP, Li C, Wang C, et al. Predictive factors of recurrence for patients with intrahepatic cholangiocarcinoma after hepatectomy. Hepatogastroenterology. 2012;59:1765–8.
    1. Hanazaki K, Kajikawa S, Shimozawa N, et al. Prognostic factors of intrahepatic cholangiocarcinoma after hepatic resection: univariate and multivariate analysis. Hepatogastroenterology. 2002;49:311–6.
    1. Endo I, Gonen M, Yopp AC, et al. Intrahepatic cholangio-carcinoma: rising frequency, improved survival, and determinants of outcome after resection. Ann Surg. 2008;248:84–96.
    1. Miwa S, Miyagawa S, Kobayashi A, et al. Predictive factors for intrahepatic cholangiocarcinoma recurrence in the liver following surgery. J Gastroenterol. 2006;41:893–900.
    1. Japan TLCSGo. Classification of primary liver cancer. Tokyo: Kanehara; 1997. Intrahepatic cholangiocarcinoma; pp. 6–7.
    1. Sobin LH, Wittekind CH, editors. TNM classification of malignant tumours. 6. Hoboken, NJ: Wiley; 2002.
    1. Graham JW, Cumsille PE, Elek-Fisk E. Methods for handling missing data. In: Schinka JA, Velicer WF, editors. Research methods in psychology. New York: John Wiley & Sons; 2003. pp. 87–114.
    1. Graham JW, Hofer SM. Multiple imputation in multivariate research. In: Little TD, editor. Modeling longitudinal and multiple-group data: practical issues, applied approaches, and specific examples. Hillsdale, NJ: Erlbaum; 2000. pp. 201–18.
    1. Raut CP, Tseng JF, Sun CC, et al. Impact of resection status on pattern of failure and survival after pancreaticoduodenectomy for pancreatic adenocarcinoma. Ann Surg. 2007;246:52–60.
    1. de Haas RJ, Wicherts DA, Flores E, et al. R1 resection by necessity for colorectal liver metastases: Is it still a contraindication to surgery? Ann Surg. 2008;248:626–37.
    1. Park SY, Kim JH, Yoon HJ, et al. Transarterial chemoembolization versus supportive therapy in the palliative treatment of unresectable intrahepatic cholangiocarcinoma. Clin Radiol. 2011;66:322–8.
    1. Ibarra RA, Rojas D, Snyder L, et al. Multicenter results of stereotactic body radiotherapy (SBRT) for non-resectable primary liver tumors. Acta Oncol. 2012;51:575–83.
    1. de Jong MC, Pulitano C, Ribero D, et al. Rates and patterns of recurrence following curative intent surgery for colorectal liver metastasis: an international multi-institutional analysis of 1669 patients. Ann Surg. 2009;250:440–8.

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