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Biliary Sclerosis after Hepatic Arterial Infusion Pump Chemotherapy for Patients with Colorectal Cancer Liver Metastasis: Incidence, Clinical Features, and Risk Factors

  • Hepatobiliary Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Hepatic arterial infusion pump chemotherapy (HAIPC) contributes to the prolonged survival of selected patients with colorectal cancer liver metastases (CRCLM). The most clinically important adverse event after HAIPC with floxuridine (FUDR) is biliary sclerosis (BS). Little is known about the etiology of BS.

Methods

HAIPC was administered to 475 consecutive patients who received HAIPC on prospective protocols from 1991 to 2008. The incidence, clinical features, variables related to demographics, comorbidity, medical history, CRCLM, surgery, chemotherapy, and laboratory data were reviewed. An analysis of factors potentially associated with BS, defined as a biliary stricture related to HAIPC requiring stent placement, was performed.

Results

The incidence of BS was 5.5% (16 of 293) in patients receiving HAIPC as an adjuvant therapy after hepatectomy, and 2% (2 of 100) in patients receiving HAIPC with FUDR for unresectable disease. The common hepatic duct was the site most frequently affected (87.5%). In patients receiving adjuvant HAIPC, BS was associated with abnormal postoperative flow scans (18.8% vs. 1.8%, P = 0.006), postoperative infectious complications (50.0% vs. 14.8%, P = 0.002), and larger dose/cycle/weight of FUDR (2.6 vs. 2.0 mg/cycle/kg, P = 0.025) than patients without BS. No patient died directly of BS. Median survival was not compromised by the development of BS (BS vs. non-BS: 61.0 months [range 6.2–171.6 months] vs. 47.2 months [range 2.4–200.8 months], P = 0.316, respectively).

Conclusions

BS is an uncommon complication after HAIPC and does not compromise survival if adequately salvaged by stenting or dilatation. Surgical complications as well as type and dose of intra-arterial chemotherapy may contribute to the development of BS.

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References

  1. Kemeny N, Fata F. Hepatic-arterial chemotherapy. Lancet Oncol. 2001;2:418–28.

    Article  PubMed  CAS  Google Scholar 

  2. Kemeny N, Capanu M, D’Angelica M, et al. Phase I trial of adjuvant hepatic arterial infusion (HAI) with floxuridine (FUDR) and dexamethasone plus systemic oxaliplatin, 5-fluorouracil and leucovorin in patients with resected liver metastases from colorectal cancer. Ann Oncol. 2009;20:1236–41.

    Article  PubMed  CAS  Google Scholar 

  3. Kemeny N, Huang Y, Cohen AM, et al. Hepatic arterial infusion of chemotherapy after resection of hepatic metastases from colorectal cancer. N Engl J Med. 1999;341:2039–48.

    Article  PubMed  CAS  Google Scholar 

  4. Kemeny N, Jarnagin W, Gonen M, et al. Phase I/II study of hepatic arterial therapy with floxuridine and dexamethasone in combination with intravenous irinotecan as adjuvant treatment after resection of hepatic metastases from colorectal cancer. J Clin Oncol. 2003;21:3303–9.

    Article  PubMed  CAS  Google Scholar 

  5. Kemeny N, Conti JA, Sigurdson E, et al. A pilot study of hepatic artery floxuridine combined with systemic 5-fluorouracil and leucovorin. A potential adjuvant program after resection of colorectal hepatic metastases. Cancer. 1993;71:1964–71.

    CAS  Google Scholar 

  6. Kemeny NE, Melendez FD, Capanu M, et al. Conversion to resectability using hepatic artery infusion plus systemic chemotherapy for the treatment of unresectable liver metastases from colorectal carcinoma. J Clin Oncol. 2009;27:3465–71.

    Article  PubMed  Google Scholar 

  7. Kemeny NE, Niedzwiecki D, Hollis DR, et al. Hepatic arterial infusion versus systemic therapy for hepatic metastases from colorectal cancer: a randomized trial of efficacy, quality of life, and molecular markers (CALGB 9481). J Clin Oncol. 2006;24:1395–403.

    Article  PubMed  CAS  Google Scholar 

  8. Kemeny N, Jarnagin W, Paty P, et al. Phase I trial of systemic oxaliplatin combination chemotherapy with hepatic arterial infusion in patients with unresectable liver metastases from colorectal cancer. J Clin Oncol. 2005;23:4888–96.

    Article  PubMed  CAS  Google Scholar 

  9. Kemeny N, Eid A, Stockman J, et al. Hepatic arterial infusion of floxuridine and dexamethasone plus high-dose Mitomycin C for patients with unresectable hepatic metastases from colorectal carcinoma. JSurgOncol. 2005;91:97–101.

    CAS  Google Scholar 

  10. Kemeny N, Gonen M, Sullivan D, et al. Phase I study of hepatic arterial infusion of floxuridine and dexamethasone with systemic irinotecan for unresectable hepatic metastases from colorectal cancer. J Clin Oncol. 2001;19:2687–95.

    PubMed  CAS  Google Scholar 

  11. Kemeny N, Conti JA, Cohen A, et al. Phase II study of hepatic arterial floxuridine, leucovorin, and dexamethasone for unresectable liver metastases from colorectal carcinoma. J Clin Oncol. 1994;12:2288–95.

    PubMed  CAS  Google Scholar 

  12. Kemeny N, Seiter K, Conti JA, et al. Hepatic arterial floxuridine and leucovorin for unresectable liver metastases from colorectal carcinoma. New dose schedules and survival update. Cancer. 1994;73:1134–42.

    CAS  Google Scholar 

  13. Allen PJ, Nissan A, Picon AI, et al. Technical complications and durability of hepatic artery infusion pumps for unresectable colorectal liver metastases: an institutional experience of 544 consecutive cases. J Am Coll Surg. 2005;201:57–65.

    Article  PubMed  Google Scholar 

  14. Daly JM, Kemeny N, Oderman P, Botet J. Long-term hepatic arterial infusion chemotherapy. Anatomic considerations, operative technique, and treatment morbidity. Arch Surg. 1984;119:936–41.

    Article  PubMed  CAS  Google Scholar 

  15. Kemeny MM, Battifora H, Blayney DW, et al. Sclerosing cholangitis after continuous hepatic artery infusion of FUDR. Ann Surg. 1985;202:176–81.

    Article  PubMed  CAS  Google Scholar 

  16. Kemeny N, Daly J, Reichman B, Geller N, Botet J, Oderman P. Intrahepatic or systemic infusion of fluorodeoxyuridine in patients with liver metastases from colorectal carcinoma. A randomized trial. Ann Intern Med. 1987;107:459–65.

    CAS  Google Scholar 

  17. Chang AE, Schneider PD, Sugarbaker PH, Simpson C, Culnane M, Steinberg SM. A prospective randomized trial of regional versus systemic continuous 5-fluorodeoxyuridine chemotherapy in the treatment of colorectal liver metastases. Ann Surg. 1987;206:685–93.

    Article  PubMed  CAS  Google Scholar 

  18. Hohn DC, Stagg RJ, Friedman MA, et al. A randomized trial of continuous intravenous versus hepatic intraarterial floxuridine in patients with colorectal cancer metastatic to the liver: the Northern California Oncology Group trial. J Clin Oncol. 1989;7:1646–54.

    PubMed  CAS  Google Scholar 

  19. Martin JK, Jr., O’Connell MJ, Wieand HS, et al. Intra-arterial floxuridine vs systemic fluorouracil for hepatic metastases from colorectal cancer. A randomized trial. Arch Surg. 1990;125:1022–7.

    Article  Google Scholar 

  20. Rougier P, Laplanche A, Huguier M, et al. Hepatic arterial infusion of floxuridine in patients with liver metastases from colorectal carcinoma: long-term results of a prospective randomized trial. J Clin Oncol. 1992;10:1112–8.

    PubMed  CAS  Google Scholar 

  21. Lorenz M, Muller HH. Randomized, multicenter trial of fluorouracil plus leucovorin administered either via hepatic arterial or intravenous infusion versus fluorodeoxyuridine administered via hepatic arterial infusion in patients with nonresectable liver metastases from colorectal carcinoma. J Clin Oncol. 2000;18:243–54.

    PubMed  CAS  Google Scholar 

  22. Kemeny MM, Adak S, Gray B, et al. Combined-modality treatment for resectable metastatic colorectal carcinoma to the liver: surgical resection of hepatic metastases in combination with continuous infusion of chemotherapy—an intergroup study. J Clin Oncol. 2002;20:1499–505.

    Article  PubMed  Google Scholar 

  23. Martin RC, Edwards MJ, McMasters KM. Morbidity of adjuvant hepatic arterial infusion pump chemotherapy in the management of colorectal cancer metastatic to the liver. Am J Surg. 2004;188:714–21.

    Article  PubMed  Google Scholar 

  24. Ludwig J, Kim CH, Wiesner RH, Krom RA. Floxuridine-induced sclerosing cholangitis: an ischemic cholangiopathy? Hepatology. 1989;9:215–8.

    Article  PubMed  CAS  Google Scholar 

  25. Michels NA. Newer anatomy of the liver and its variant blood supply and collateral circulation. Am J Surg. 1966;112:337–47.

    Article  PubMed  CAS  Google Scholar 

  26. Fong Y, Fortner J, Sun RL, Brennan MF, Blumgart LH. Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. Ann Surg. 1999;230:309–18.

    Article  PubMed  CAS  Google Scholar 

  27. Lee YM, Kaplan MM. Primary sclerosing cholangitis. N Engl J Med. 1995;332:924–33.

    Article  PubMed  CAS  Google Scholar 

  28. Angulo P, Lindor KD. Primary sclerosing cholangitis. Hepatology. 1999;30:325–32.

    Article  PubMed  CAS  Google Scholar 

  29. Lillemoe KD. Benign post-operative bile duct strictures. Baillieres Clin Gastroenterol. 1997;11:749–79.

    Article  PubMed  CAS  Google Scholar 

  30. Cantwell CP, Pena CS, Gervais DA, Hahn PF, Dawson SL, Mueller PR. Thirty years’ experience with balloon dilation of benign postoperative biliary strictures: long-term outcomes. Radiology. 2008;249:1050–7.

    Article  PubMed  Google Scholar 

  31. Costamagna G, Shah SK, Tringali A. Current management of postoperative complications and benign biliary strictures. Gastrointest Endosc Clin N Am. 2003;13:635–48.

    Article  PubMed  Google Scholar 

  32. Goere D, Deshaies I, de Baere T, et al. Prolonged survival of initially unresectable hepatic colorectal cancer patients treated with hepatic arterial infusion of oxaliplatin followed by radical surgery of metastases. Ann Surg. 2010;251:686–91.

    Article  PubMed  Google Scholar 

  33. Tsimberidou AM, Fu S, Ng C, et al. A phase 1 study of hepatic arterial infusion of oxaliplatin in combination with systemic 5-fluorouracil, leucovorin, and bevacizumab in patients with advanced solid tumors metastatic to the liver. Cancer. 2010;116:4086–94.

    Article  PubMed  CAS  Google Scholar 

  34. Bouchahda M, Adam R, Giacchetti S, et al. Rescue chemotherapy using multidrug chronomodulated hepatic arterial infusion for patients with heavily pretreated metastatic colorectal cancer. Cancer. 2009;115:4990–9.

    Article  PubMed  CAS  Google Scholar 

  35. Boige V, Malka D, Elias D, et al. Hepatic arterial infusion of oxaliplatin and intravenous LV5FU2 in unresectable liver metastases from colorectal cancer after systemic chemotherapy failure. Ann Surg Oncol. 2008;15:219–26.

    Article  PubMed  Google Scholar 

  36. Ducreux M, Ychou M, Laplanche A, et al. Hepatic arterial oxaliplatin infusion plus intravenous chemotherapy in colorectal cancer with inoperable hepatic metastases: a trial of the gastrointestinal group of the Federation Nationale des Centres de Lutte Contre le Cancer. J Clin Oncol. 2005;23:4881–7.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Kaori Ito MD, Hiromichi Ito MD, Peter J. Allen MD, FACS, Philip B. Paty MD, FACS, Yuman Fong MD, FACS, Ronald P. DeMatteo MD, FACS, Leslie H. Blumgart MD, FACS, FCRS, William R. Jarnagin MD, FACS & Michael I. D’Angelica MD, FACS

  2. Department of Surgery, Michigan State University, Lansing, MI, USA

    Kaori Ito MD & Hiromichi Ito MD

  3. Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Nancy E. Kemeny MD

  4. Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Mithat Gonen PhD

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  1. Kaori Ito MD
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  2. Hiromichi Ito MD
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  3. Nancy E. Kemeny MD
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Correspondence to Michael I. D’Angelica MD, FACS.

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Ito, K., Ito, H., Kemeny, N.E. et al. Biliary Sclerosis after Hepatic Arterial Infusion Pump Chemotherapy for Patients with Colorectal Cancer Liver Metastasis: Incidence, Clinical Features, and Risk Factors. Ann Surg Oncol 19, 1609–1617 (2012). https://doi.org/10.1245/s10434-011-2102-8

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  • DOI: https://doi.org/10.1245/s10434-011-2102-8

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