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Liver Resection for Primarily Unresectable Colorectal Metastases Downsized by Chemotherapy

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Journal of Gastrointestinal Surgery Aims and scope

Abstract

This study was performed prospectively to assess the effect of systemic chemotherapy (FOLFIRI protocol) in patients with initially unresectable colorectal liver metastases (CRLM) and, after performing liver resection in patients with downsized metastases, to compare the postoperative and long-term results with those of patients with primarily resectable CRLM. Records from a prospective database including all consecutive admissions for CRLM between June 2000 and June 2004 were reviewed. The analysis addressed all patients who underwent hepatectomy for primarily resectable CRLM (Group A), or underwent chemotherapy for primarily unresectable CRLM and among these, particularly the patients who were finally resected after downsizing of CRLM (Group B). There were 60 primarily resected patients (Group A). Forty-two other patients underwent chemotherapy; after an average of nine courses, 18 of them (42.8%) with significantly downsized lesions were explored and 15 (35.7%, Group B) were resected, whereas three had peritoneal metastases. Group B differed from Group A for a significantly higher rate of synchronous CRLM upon diagnosis of colorectal cancer, a larger size of CRLM upon evaluation in our center, and a lower rate of major hepatectomies (20.0% vs. 51.6 %) at surgery. No patient in Group B had positive margins of resection. Operative mortality was nil and morbidity was 20.0% in both groups. In Group B vs. Group A median survival after hepatectomy was 46 vs. 47 months (n.s), 3-year survival rate was 73% vs. 71% (n.s.), disease-free survival rate was 31% vs. 58% (p = 0.04) and, at a median follow-up of 34 months, tumor recurrence rate was 53.3% vs. 28.3% (n.s.). Four out of the eight Group B patients with recurrence underwent a re-resection, and were alive at 9 to 67 months after the first resection. These results show that in about one-third of the patients with primarily unresectable CRLM, downsizing of the lesions by chemotherapy (FOLFIRI protocol) permitted a subsequent curative resection. In these patients, operative risk and survival did not differ from the figures observed in primarily resectable patients and, in spite of a lower disease-free survival with more frequent recurrence, re-resection still represented a valid option to continue treatment.

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References

  1. Boyle P, Langman JS. ABC of colorectal cancer: Epidemiology. BMJ 2000;321:805–808.

    Article  PubMed  CAS  Google Scholar 

  2. Steele G, Jr, Ravikumar TS. Resection of hepatic metastases from colorectal cancer: Biologic perspectives. Annals of Surgery 1989;210:127–138.

    Article  PubMed  Google Scholar 

  3. Scheele J. Hepatectomy for liver metastases. British Journal of Surgery 1993;80:274–276.

    Article  PubMed  CAS  Google Scholar 

  4. Scheele J, Stangl R, Altendorf-Hofmann A, Paul M. Resection of colorectal liver metastases. World Journal of Surgery 1995;19:59–71.

    Article  PubMed  CAS  Google Scholar 

  5. Jaeck D, Bachellier P, Guiguet M, Boudjema K, Vaillant JC, Balladur P, Nordlinger B. Long-term survival following resection of colorectal hepatic metastases: Association Francaise de Chirurgie. British Journal of Surgery 1997;84:977–980.

    Article  PubMed  CAS  Google Scholar 

  6. 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. Annals of Surgery 1999;230:309–318.

    Article  PubMed  CAS  Google Scholar 

  7. Adam R, Pascal G, Azoulay D, Tanaka K, Castaing D, Bismuth H. Liver resection for colorectal metastases: The third hepatectomy. Annals of Surgery 2003;238:871–883.

    Article  PubMed  Google Scholar 

  8. Stangl R, Altendorf-Hofmann A, Charnely RM, Scheele J. Factors influencing the natural history of colorectal liver metastases. Lancet 1994;343:1405–1410.

    Article  PubMed  CAS  Google Scholar 

  9. Baden H, Andersen B. Survival of patients with untreated liver metastases from colorectal cancer. Scandinavian Journal of Gastroenterology 1975;10:221–223.

    PubMed  CAS  Google Scholar 

  10. Wagner JS, Adson MA, Van Heerden JA, Adson MH, Ilstrup DM. The natural history of hepatic metastases from colorectal cancer. A comparison with resective treatment. Annals of Surgery 1984;199:502–508.

    Article  PubMed  CAS  Google Scholar 

  11. Ballantyne GH, Quin J. Surgical treatment of liver metastases in patients with colorectal cancer. Cancer 1993;71:4252–4266.

    Article  PubMed  CAS  Google Scholar 

  12. Gorog D, Toth A, Weltner J. Prognosis of untreated liver metastases from rectal cancer. Acta Chirurgica Hungarica 1997;36:106–107.

    PubMed  CAS  Google Scholar 

  13. Adam R. Chemotherapy and surgery: new perspectives on the treatment of unresectable liver metastases. Annals of Oncology 2003;14(Suppl 2):ii13–ii16.

    PubMed  Google Scholar 

  14. Giacchetti S, Itzhaki M, Gruia G, Adam R, Zidani R, Kunstlinger F, Brienza S, Alafaci E, Bertheault-Cvitkovic F, Jasmin C, Reynes M, Bismuth H, Misset JL, Lévi F. Long-term survival of patients with unresectable colorectal cancer liver metastases following infusional chemotherapy with 5-fluorouracil, leucovorin, oxaliplatin and surgery. Annals of Oncology 1999;10:663–669.

    Article  PubMed  CAS  Google Scholar 

  15. Fusai G, Davidson BR. Strategies to increase the resectability of liver metastases from colorectal cancer. Digestive Surgery 2003;20:481–496.

    Article  PubMed  CAS  Google Scholar 

  16. Bismuth H, Adam R, Lévi F, Farabos C, Waechter F, Castaing D, Majno P, Engerrman L. Resection of nonresectable liver metastases from colorectal cancer after neoadjuvant chemotherapy. Annals of Surgery 1996;224:509–520.

    Article  PubMed  CAS  Google Scholar 

  17. Pozzo C, Basso M, Cassano A, Quirino M, Schinzari G, Trigila N, Vellone M, Giuliante F, Nuzzo G, Barone C. Neoadjuvant treatment of unresectable liver disease with irinotecan and 5-flurouracil plus folinic acid in colorectal cancer patients. Annals of Oncology 2004;15:933–939.

    Article  PubMed  CAS  Google Scholar 

  18. Fong Y. Surgical therapy of hepatic colorectal metastasis. CA Cancer J Clin 1999;49:231–235.

    PubMed  CAS  Google Scholar 

  19. Erlichman C, Fine S, Wong A, Elhakim T. A randomized trial of fluorouracil and folinic acid in patients with metastatic colorectal carcinoma. Journal of Clinical Oncology 1988;6:469–475.

    PubMed  CAS  Google Scholar 

  20. Lévi F, Zidani R, Misset JL. Randomised multicentre trial of chronotherapy with oxaliplatin, fluorouracil, and folinic acid in metastatic colorectal cancer: International Organization for Cancer Chronotherapy. Lancet 1997;350:681–686.

    Article  PubMed  Google Scholar 

  21. De Gramont A, Figer A, Seymour M, Homerin M, Hmissi A, Cassidy J, Boni C, Cortes-Funes H, Cervantes A, Freyer G, Papamichael D, Le Bail, N, Louvet C, Hendler D, de Braud F, Wilson C, Morvan F, Bonnetti A. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. Journal of Clinical Oncology 2000;18:2938–2947.

    PubMed  Google Scholar 

  22. Douillard JY, Cunningham D, Roth AD, Navarro M, James RD, Karasek P, Jandik P, Iveson T, Carmichael J, Alakl M, Gruia G, Awad L, Rougier P. Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: A multicentre randomised trial. Lancet 2000;355:1041–1047.

    Article  PubMed  CAS  Google Scholar 

  23. Saltz LB, Cox JV, Blanke C, Rosen LS, Fehrenbacher L, Moore MJ, Maroun JA, Ackland SP, Locker PK, Pirotta N, Elfring GL, Miller LL. Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. Irinotecan Study Group. New England Journal of Medicine 2000;343:905–914.

    Article  PubMed  CAS  Google Scholar 

  24. Giacchetti S, Perpoint B, Zidani R, Le Bail N, Faggiuolo R, Focan C, Chollet P, Llory JF, Letourneau Y, Coudert B, Bertheaut-Cvitkovic F, Larregain-Fournier D, Le Rol A, Walter S, Adam R, Misset JL, Lévi F. Phase III multicenter randomized trial of oxaliplatin added to chronomodulated fluorouracil-leucovorin as first-line treatment of metastatic colorectal cancer. Journal of Clinical Oncology 2000;18:136–147.

    PubMed  CAS  Google Scholar 

  25. Tournigand C, Andre T, Achille E, Lledo G, Flesh M, Mery-Mignard D, Quinaux E, Couteau C, Buyse M, Ganem G, Landi B, Colin P, Louvet C, de Gramont A, FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: A randomized GERCOR study. Journal of Clinical Oncology 2004;22:229–237.

    Article  PubMed  CAS  Google Scholar 

  26. Lévi F, Misset JL, Brienza S, Adam R, Metzger G, Itzakhi M, Causannel JP, Kunstlinger F, Lecourturier S, Descorps-Declere A, Jasmin C, Bismuth H, Reinberg A. A chronopharmacologic phase II clinical trial with 5-fluorouracil, folinic acid, and oxaliplatin using an ambulatory multichannel programmable pump. High antitumor effectiveness against metastatic colorectal cancer. Cancer 1992;69:893–900.

    Article  PubMed  Google Scholar 

  27. Shankar A, Leonard P, Renaut AJ, Lederman J, Lees WR, Gillams AR, Harrison E, Taylor I, Neo-adjuvant therapy improves resectability rates for colorectal liver metastases. Annals of the Royal College of Surgeons of England 2001;83:85–88.

    PubMed  CAS  Google Scholar 

  28. Adam R, Delvart V, Pascal G, Valeanu A, Castaing D, Azoulay D, Giacchetti S, Paule B, Kunstlinger F, Ghémard O, Lévi F, Bismuth H. Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy: A model to predict long-term survival. Annals of Surgery 2004;240:644–657.

    Article  PubMed  Google Scholar 

  29. World Health Organization. Handbook for reporting results of cancer treatment. Geneva: World Health Organization, 1979. WHO offset publication no. 48.

  30. Nuzzo G, Giuliante F, Vellone M, De Cosmo G, Ardito F, Murazio M, D’Acapito F, Giovannini I. Pedicle clamping with ischemic preconditioning in liver resection. Liver Transplantation 2004;10(2 Suppl 1):S53–57.

    Article  PubMed  Google Scholar 

  31. Nuzzo G, Giuliante F, Giovannini I, Vellone M, De Cosmo G, Capelli G. Liver resections with or without pedicle clamping. American Journal of Surgery 2001;181:238–246.

    Article  PubMed  CAS  Google Scholar 

  32. Elias D, Ouellet JF, de Baere T, Lasser P, Roche A. Preoperative selective portal vein embolization before hepatectomy for liver metastases: Long-term results and impact on survival. Surgery 2002;131:294–299.

    Article  PubMed  Google Scholar 

  33. Azoulay D, Castaing D, Smail A, Adam R, Cailliez V, Laurent A, Lemoine A, Bismuth H. Resection of nonresectable liver metastases from colorectal cancer after percutaneous portal vein embolization. Annals of Surgery 2000;4:480–486.

    Article  Google Scholar 

  34. Abdalla EK, Vauthey JN, Ellis LM, Ellis V, Pollock R, Broglio KR, Hess K, Curley SA. Recurrence and outcomes following hepatic resection, radiofrequency ablation, and combined resection/ablation for colorectal liver metastases. Annals of Surgery 2004;239:818–825.

    Article  PubMed  Google Scholar 

  35. Adam R, Akpinar E, Johann M, Kunstlinger F, Majno P, Bismuth H. Place of cryosurgery in the treatment of malignant liver tumors. Annals of Surgery 1997;225:39–48.

    Article  PubMed  CAS  Google Scholar 

  36. Jaeck D, Oussoultzoglou E, Rosso E, Greget M, Weber JC, Bachellier P. A two-stage hepatectomy procedure combined with portal vein embolization to achieve curative resection for initially unresectable multiple and bilobar colorectal liver metastases. Annals of Surgery 2004;240:1037–1049.

    Article  PubMed  Google Scholar 

  37. Adam R, Laurent A, Azoulay D, Castaing D, Bismuth H. Two-stage hepatectomy: A planned strategy to treat irresectable liver tumors. Annals of Surgery 2000;232:777–785.

    Article  PubMed  CAS  Google Scholar 

  38. Adam R, Avisar E, Ariche A, Giacchetti S, Azoulay D, Castaing D, Kunstlinger F, Lévi F, Bismuth H. Five-year survival following hepatic resection after neoadjuvant therapy for nonresectable colorectal [liver] metastases. Annals of Surgical Oncol 2001;8:347–353.

    Article  CAS  Google Scholar 

  39. Rivoire M, De Cian F, Meeus P, Negrier S, Sebban H, Kaemmerlen P. Combination of neoadjuvant chemotherapy with cryotherapy and surgical resection for the treatment of unresectable liver metastases from colorectal carcinoma. Cancer 2002;95:2283–2292.

    Article  PubMed  CAS  Google Scholar 

  40. Adam R, Lucidi V, Bismuth H. Hepatic colorectal metastases: Methods of improving resectability. Surgical Clinics of North America 2004;84:659–671.

    Article  PubMed  Google Scholar 

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Nuzzo, G., Giuliante, F., Ardito, F. et al. Liver Resection for Primarily Unresectable Colorectal Metastases Downsized by Chemotherapy. J Gastrointest Surg 11, 318–324 (2007). https://doi.org/10.1007/s11605-006-0070-2

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