Skip to main content
SpringerLink
Log in

Kolorektale Leberfiliae

Neoadjuvante Chemotherapie aus internistischer und chirurgischer Sicht

Colorectal liver metastases

Neoadjuvant chemotherapy: aspects of medical and surgical oncology

  • Schwerpunkt: Lebertumoren
  • Published:
Der Internist Aims and scope Submit manuscript

Zusammenfassung

Kolorektale Lebermetastasen werden bei 15–20% der Patienten zum Zeitpunkt der Erstdiagnose und bei weiteren 20–30% der Patienten im weiteren Verlauf diagnostiziert. Nach radikaler Resektion ist eine Heilung möglich, dabei liegen die 5-Jahres-Überlebensraten bei 30–50%. Die Resektabilität kann durch chirurgische Verfahren gesteigert werden, beispielsweise mit 2-zeitiger Hepatektomie oder Pfortaderembolisation. Darüber hinaus wird seit Einführung der modernen systemischen Chemotherapie mit unterschiedlichen Kombinationen von Oxaliplatin, Irinotecan, Bevacizumab und Cetuximab vermehrt die sekundäre Resektabilität vormals irresektabler Metastasen beobachtet—in Korrelation zu den Ansprechraten der Chemotherapie, die bis zu 80% betragen können. Histologische Veränderungen der Leber wie sinusoidale Obstruktion (z. B. nach Oxaliplatin) oder Steatohepatitis (z. B. nach Irinotecan) wurden berichtet. Hierdurch kann im Einzelfall das operative Risiko einer Leberteilresektion nach neoadjuvanter Therapie gesteigert sein. Der Stellenwert einer neoadjuvanten Therapie bei resektablen Metastasen ist zzt. noch nicht gesichert.

Abstract

Colorectal liver metastases are detected in 15–20% of patients at the time of diagnosis of the primary tumor, they develop in an additional 20–30% of patients during further course of the disease. Radical resection enables 5-year survival rates of 30–50%. Resectability may be increased by surgical techniques including two-stage hepatectomy and portal vein embolization. Furthermore, modern chemotherapy including various combinations of oxaliplatin, irinotecan, bevacizumab, and cetuximab has led to secondary resectability correlating to response rates which may be up to 80%. Changes of hepatic histology such as sinusoidal obstruction (e.g. following oxaliplatin) or steatohepatitis (e.g. following irinotecan) have been described. Individually, this may increase the risk of subsequent liver resection. As of today the role of neoadjuvant chemotherapy for resectable lesions has not been definitively confirmed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Abb. 1
Abb. 2
Abb. 3

Literatur

  1. Abdalla EK, Vauthey JN, Ellis LM et al. (2004) Recurrence and outcomes following hepatic resection, radiofrequency ablation, and combined resection/ablation for colorectal liver metastases. Ann Surg 239: 818–827

    Article  PubMed  Google Scholar 

  2. Adam R, Avisar E, Ariche A et al. (2001) Five-year survival following hepatic resection after neoadjuvant therapy for nonresectable colorectal metastases. Ann Surg Oncol 8: 347–353

    PubMed  Google Scholar 

  3. Adam R, Delvart V, Pascal G et al. (2004) Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy: a model to predict long-term survival. Ann Surg 240: 644–657

    PubMed  Google Scholar 

  4. Adam R, Pascal G, Castaing D et al. (2004) Tumor progression while on chemotherapy: a contraindication to liver resection for multiple colorectal metastases? Ann Surg 240: 1052–1061

    Article  PubMed  Google Scholar 

  5. Bechstein WO, Golling M (2005) Chirurgische Resektion kolorektaler Lebermetastasen. Was ist Standard? Chirurg 76: 543–551

    Article  PubMed  Google Scholar 

  6. Benoist S, Brouquet A, Penna C et al. (2006) Complete response of colorectal liver metastases after chemotherapy: does it mean cure? J Clin Oncol 24: 3939–3945

    Article  PubMed  Google Scholar 

  7. Capussotti L, Muratore A, Mulas MM, Massucco P, Aglietta M (2006) Neoadjuvant chemotherapy and resection for initially irresectable colorectal liver metastases. Br J Surg 93: 1001–1006

    Article  PubMed  Google Scholar 

  8. Ellis LM, Curley SA, Grothey A (2005) Surgical resection after downsizing of colorectal liver metastasis in the era of bevacizumab. J Clin Oncol 23: 4853–4855

    Article  PubMed  Google Scholar 

  9. Fernandez FG, Ritter J, Goodwin JW, Linehan DC, Hawkins WG, Strasberg SM (2005) Effect of steatohepatitis associated with irinotecan or oxaliplatin pretreatment on respectability of hepatic colorectal metastases. J Am Coll Surg 200: 845–853

    Article  PubMed  Google Scholar 

  10. Folprecht G, Grothey A, Alberts S, Raab HR, Kohne CH (2005) Neoadjuvant treatment of unresectable colorectal liver metastases: correlation between tumour response and resection rates. Ann Oncol 16: 1311–1399

    Article  PubMed  Google Scholar 

  11. Folprecht G, Lutz MP, Schoffski P et al. (2006) Cetuximab and irinotecan/5-fluorouracil/folinic acid is a safe combination for the first-line treatment of patients with epidermal growth factor receptor expressing metastatic colorectal carcinoma. Ann Oncol 17: 450–456

    Article  PubMed  Google Scholar 

  12. Garden J, Rees M, Poston G et al. (2006) Guidelines for resection of colorectal cancer liver metastases. Gut 55: 1–8

    Article  PubMed  Google Scholar 

  13. Giacchetti S, Itzhaki M, Gruia G et al. (1999) Long-term survival of patients with unresectable colorectal cancer liver metastases following infusional chemotherapy with 5-fluorouracil, leucovorin, oxaliplatin and surgery. Ann Oncol 10: 663–669

    Article  PubMed  Google Scholar 

  14. Goldberg RM, Sargent DJ, Morton RF et al. (2004) A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol 22: 23–30

    Article  PubMed  Google Scholar 

  15. Grobmeyer SR, Wang L, Gonen M et al. (2006) Perihepatic lymph node assessment in patients undergoing partial hepatectomy for malignancy. Ann Surg 244: 260–264

    Article  PubMed  Google Scholar 

  16. Gruenberger T, Sorbye H, Debois M et al. (2006) Tumor response to pre-operative chemotherapy (CT) with FOLFOX-4 for resectable colorectal cancer liver metastases (LM) Interim results of EORTC Intergroup randomized phase III study 40983. J Clin Oncol, ASCO Annual Meeting Proceedings 24: 3500

  17. Hamady ZZR, Cameron IC, Wyatt J, Prasad RK, Toogood GJ, Lodge JPA (2006) Resection margin in patients undergoing hepatectomy for colorectal liver metastasis: a critical appraisal of the 1 cm rule. Eur J Surg Oncol 32: 557–563

    Article  PubMed  Google Scholar 

  18. Hurwitz H, Fehrenbacher L, Novotny W et al. (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350: 2335–2342

    Article  PubMed  Google Scholar 

  19. Jaeck D, Oussoultzoglou E, Rosso E, Greget M, WeberJC, Bachellier P (2004) A two-stage hepatectomy procedure combined with portal vein embolization to achieve curative resection for initially unresectable multiple and bilobar colorectal liver metastases. Ann Surg 240: 1037–1051

    Article  PubMed  Google Scholar 

  20. Lorenz M, Muller HH, Schramm H et al. (1998) Randomized trial of surgery versus surgery followed by adjuvant hepatic arterial infusion with 5-fluorouracil and folinic acid for liver metastases of colorectal cancer. German Cooperative on Liver Metastases (Arbeitsgruppe Lebermetastasen) Ann Surg 228: 756–762

    Google Scholar 

  21. Lorenz M, Staib-Sebler E, Gog C et al. (2003) Prospective pilot study of neoadjuvant chemotherapy with 5-fluorouracil, folinic acid and oxaliplatin in resectable liver metastases of colorectal cancer. Analysis of 42 neoadjuvant chemotherapies. Zentralbl Chir 128: 87–94

    Article  PubMed  Google Scholar 

  22. Manfredi S, Lepage C, Hatem C, Coatmeur O, Faivre J, Bouvier AM (2006) Epidemiology and management of liver metastases from colorectal cancer. Ann Surg 244: 254–259

    Article  PubMed  Google Scholar 

  23. Masi G, Cupiini S, Marcucci L et al. (2006) Treatment with 5-fluorouracil/folinic acid, oxaliplatin, and irinotecan enables surgical resection of metastases in patients with initially unresectable metastatic colorectal cancer. Ann Surg Oncol 13: 58–65

    Article  PubMed  Google Scholar 

  24. Mentha G, Majno PE, Andres A, Rubbia-Brandt L, Morel P, Roth AD (2006) Neoadjuvant chemotherapy and resection of advance synchronous liver metastases before treatment of the colorectal primary. Br J Surg 93: 872–878

    Article  PubMed  Google Scholar 

  25. Meta-analysis Group In Cancer (1998) Efficacy of intravenous continuous infusion of fluorouracil compared with bolus administration in advanced colorectal cancer. J Clin Oncol 16: 301–308

    PubMed  Google Scholar 

  26. Mitry E, Fields A, Bleiberg H et al. (2006) Adjuvant chemotherapy after potentially curative resection of metastases from colorectal cancer. A meta-analysis of two randomized trials. J Clin Oncol, ASCO Annual Meeting Proceedings 24: 3524

  27. Nordlinger B, Sorbye H, Debois M et al. (2005) Feasibility and risks of pre-operative chemotherapy (CT) with FOLFOX 4 and surgery for resectable colorectal cancer liver metastases (LM) Interim results of the EORTC Intergroup randomized phase III study 40983. J Clin Oncol, ASCO Annual Meeting Proceedings 23: 3528

  28. Oussoultzoglu E, Bachellier P, Rosso E et al. (2006) Right portal vein embolization before right hepatectomy for unilobar colorectal liver metastases reduces the intrahepatic recurrence rate. Ann Surg 244: 71–79

    Article  PubMed  Google Scholar 

  29. Pawlik TM, Abdalla EK, Ellis LM, Vauthey JN, Curley SA (2006) Debunking dogma: Surgery for four or more colorectal liver metastases is justified. J Gastrointest Surg 10: 240–248

    Article  PubMed  Google Scholar 

  30. Poston GJ, Adam R, Alberts S et al. (2005) OncoSurge: A strategy for improving resectability with curative intent in metastatic colorectal cancer. J Clin Oncol 23: 7125–7134

    Article  PubMed  Google Scholar 

  31. Rubbia-Brandt L, Audard V, Sartoretti P et al. (2004) Oxaliplatin may induce severe hepatic sinusoidal obstruction (veno-occlusive lesion) in treatment of advanced colorectal cancer. Ann Oncol 15: 460–466

    Article  PubMed  Google Scholar 

  32. Selzner M, Hany TF, Wildbrett P, McCormack L, Kadry Z, Clavien PA (2004) Does the novel PET/CT imaging modality impact on the treatment of patients with metastatic colorectal cancer in the liver? Ann Surg 240: 1027–1036

    Article  PubMed  Google Scholar 

  33. Sperti E, Faggiuolo R, Gerbino A et al. (2006) Outcome of metastatic colroectal cancer: analysis of a consecutive series of 229 patients. The impact of a multidisciplinary approach. Dis Colon Rectum 49: 1596–1601

    Article  PubMed  Google Scholar 

  34. Titu LV, Breen DJ, Nicholson AA, Hartley J, Monson JRT (2006) Is routine magnetic resonance imaging justified for the early detection of respectable liver metastases from colorectal cancer? Dis Colon Rectum 49: 810–815

    Article  PubMed  Google Scholar 

  35. Tournigand C, Andre T, Achille E et al. (2004) FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol 15: 229–237

    Google Scholar 

  36. Vauthey JN, Abdalla EK (2006) Unresectable hepatic colorectal metastases: need for new surgical strategies. Ann Surg Oncol 13: 5–6

    Article  PubMed  Google Scholar 

  37. Vauthey JN, Pawlik TM, Ribero D et al. (2006) Chemotherapy regimen predicts steatohepatitits and an increase in 90-day mortality after surgery for hepatic colorectal metastases. J Clin Oncol 24: 2065–2072

    Google Scholar 

  38. Wade TP, Virgo KS, Li MJ, Callander PW, Longo WE, Johnson FE (1996) Outcome after detection of metastatic carcinoma of the colon and rectum in a national hospital system. J Am Coll Surg 182: 353–361

    PubMed  Google Scholar 

  39. Yan TD, Padang R, Xia H, Zhao J, Li J, Morris DL (2006) Management of involved or close resection margins in 120 patients with colorectal liver metastases: edge cryotherapy can achieve long-term survival. Am J Surg 191: 735–742

    Article  PubMed  Google Scholar 

  40. Yedibela S, Elad L, Wein A et al. (2005) Neoadjuvant chemotherapy does not increase postoperative complication rate after resection of colorectal liver metastases. Eur J Surg Oncol 31: 141–146

    Article  PubMed  Google Scholar 

  41. Zorzi D, Mullen JT, Abdalla EK et al. (2006) Comparison between hepatic wedge resection and anatomic resection for colorectal liver metastases. J Gastrointest Surg 10: 86–94

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medizinische Klinik, Knappschaftskrankenhaus, Ruhruniversität, 44892, In der Schornau 23–25, Bochum, Deutschland

    Anke C. Reinacher-Schick

  2. Klinik für Allgemein- und Gefäßchirurgie, Klinikum der Johann Wolfgang Goethe-Universität, Deutschland, Frankfurt

    W.O. Bechstein

Authors
  1. Anke C. Reinacher-Schick
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. W.O. Bechstein
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anke C. Reinacher-Schick.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Reinacher-Schick, A., Bechstein, W. Kolorektale Leberfiliae. Internist 48, 51–58 (2007). https://doi.org/10.1007/s00108-006-1770-0

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00108-006-1770-0

Schlüsselwörter

Keywords

Search

Navigation