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Curative in situ ablation of colorectal liver metastases—experimental and clinical implementation

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Abstract

Introduction

In situ ablation of colorectal liver metastases is frequently assessed for palliative treatment only. The establishment of clinically relevant lesion size and a lack of long-term survival data were regarded as main limitations to using them with curative intention. In contrast to surgical liver resection, whose oncological findings seem to have remained unchanged over the years, the in situ ablation methods have considerably changed technically and clinically in the last few years.

Objective

The aim of the paper was to point out experimental and clinical data underlining the impact of in situ ablation for potentially curative treatment of colorectal liver metastases.

Discussion

On the basis of experimental data, the aim of complete local tumor control (R0 ablation) can only be obtained if additional energy is applied after reaching the tumor-adapted maximal coagulation volume. Analogous to the oncological safety margin in surgical resection, we defined this decisive energy difference as the “energy safety margin” for in situ ablation. The energy safety margin is the energy that must be additionally applied after reaching the plateau in the energy/volume curve to achieve complete tumor coagulation. In addition to that, in situ ablation should be combined with temporary interruption of hepatic perfusion whenever possible to prevent intralesional recurrences. In this way, the thermoprotective mechanism of hepatic perfusion can be effectively eliminated. With restrictions, the survival data after ablation in specialized centers is comparable to surgical resection with concomitantly lower morbidity and mortality. Based on recent findings and with the corresponding expertise in the field of ablation and state-of-the-art equipment, ablation is, thus, an alternative to surgical resection. The combined application of surgical resection and ablation is also a suitable method for increasing the R0 rate and thus helps improve the prognosis of treated patients. In summary, it can be said that in situ ablation is a useful expansion of the therapeutic spectrum of liver metastases and can be applied as an alternative to or in combination with surgical resection.

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References

  1. Donckier V, Van Laethem JL, Goldman S, Van Gansbeke D, Feron P, Ickx B, Wikler D, Gelin M (2003) [F-18] fluorodeoxyglucose positron emission tomography as a tool for early recognition of incomplete tumor destruction after radiofrequency ablation for liver metastases. J Surg Oncol 84(4):215–223 (Dec)

    Article  PubMed  Google Scholar 

  2. Wacker FK, Reither K, Ritz JP, Roggan A, Germer CT, Wolf KJ (2001) MR-guided interstitial laser-induced thermotherapy of hepatic metastases combined with arterial blood flow reduction: technique and first clinical results in an open MR system. J Magn Reson Imaging 13(1):31–36 (Jan)

    Article  PubMed  CAS  Google Scholar 

  3. Seifert JK, Springer A, Baier P, Junginger T (2005) Liver resection or cryotherapy for colorectal liver metastases: a prospective case control study. Int J Colorectal Dis 20(6):507–520 (Nov)

    Article  PubMed  Google Scholar 

  4. Dong B, Liang P, Yu X, Su L, Yu D, Cheng Z, Zhang J (2003) Percutaneous sonographically guided microwave coagulation therapy for hepatocellular carcinoma: results in 234 patients. AJR Am J Roentgenol 180(6):1547–1555 (Jun)

    PubMed  Google Scholar 

  5. Kurokohchi K, Masaki T, Miyauchi Y, Funaki T, Yoneyama H, Miyoshi H, Yoshida S, Himoto T, Morishita A, Uchida N, Watanabe S, Kuriyama S (2004) Percutaneous ethanol and lipiodol injection therapy for hepatocellular carcinoma. Int J Oncol 24(2):381–387 (Feb)

    PubMed  CAS  Google Scholar 

  6. Birth M, Hildebrand P, Dahmen G, Ziegler A, Broring DC, Hillert C, Bruch HP (2004) Present state of radio frequency ablation of liver tumors in Germany (in German). Chirurg 75(4):417–423 (Apr)

    Article  PubMed  CAS  Google Scholar 

  7. Ritz JP, Lehmann KS, Reissfelder C, Albrecht T, Frericks B, Zurbuchen U, Buhr HJ (2006) Bipolar radiofrequency ablation of liver metastases during laparotomy. First clinical experiences with a new multipolar ablation concept. Int J Colorectal Dis 21(1):25–32 (Jan)

    Article  PubMed  Google Scholar 

  8. Ritz JP, Lehmann K, Isbert C, Roggan A, Germer CT, Buhr HJ (2005) Effectivity of laser-induced thermotherapy: In vivo comparison of arterial microembolization and complete hepatic inflow occlusion. Lasers Surg Med 36(3):238–244 (Feb 11)

    Article  PubMed  Google Scholar 

  9. Lee JM, Rhim H, Han JK, Youn BJ, Kim SH, Choi BI (2004) Dual-probe radiofrequency ablation: an in vitro experimental study in bovine liver. Invest Radiol 39(2):89–96 (Feb)

    Article  PubMed  Google Scholar 

  10. Ritz JP, Roggan A, Isbert C, Muller G, Buhr HJ, Germer CT (2001) Optical properties of native and coagulated porcine liver tissue between 400 and 2400 nm. Lasers Surg Med 29(3):205–212

    Article  PubMed  CAS  Google Scholar 

  11. Germer CT, Isbert C, Albrecht D, Ritz JP, Schilling A, Roggan A, Wolf KJ, Müller G, Buhr HJ (1998) Laser-induced thermotherapy (LITT) for the treatment of liver metastases—correlation of gadolinium–DTPA-enhanced MRI with histmorphological findings to determine for follow-up monitoring. Surg Endosc 12:1317–1325

    Article  PubMed  CAS  Google Scholar 

  12. Matsuda H, Sugimachi K, Kuwano H, Mori M (1989) Hyperthermia, tissue microcirculation, and temporarily increased thermosensitivity in VX2 carcinoma in rabbit liver. Cancer Res 49(10):2777–2872 (May 15)

    PubMed  CAS  Google Scholar 

  13. Isbert C, Roggan A, Ritz JP, Muller G, Buhr HJ, Lehmann KS, Germer CT (2001) Laser-induced thermotherapy: intra- and extralesionary recurrence after incomplete destruction of experimental liver metastases. Surg Endosc 15(11):1320–1326 (Nov)

    Article  PubMed  CAS  Google Scholar 

  14. Germer CT, Albrecht D, Isbert C, Ritz JP, Roggan A, Buhr HJ (1999) Diffusing fiber tip for the minimal-invasive treatment of liver tumors by interstitial laser coagulation (ILC) an experimental ex-vivo study. Lasers Med Sci 14:32–39

    Article  Google Scholar 

  15. Matthewson K, Barton T, Lewin MR, O'Sullivan JP, Northfield TC, Bown SG (1988) Low power interstitial Nd YAG laser photocoagulation in normal and neoplastic rat colon. Gut 29(1):27–34 (Jan)

    PubMed  CAS  Google Scholar 

  16. Isbert C, Ritz JP, Schilling A, Roggan A, Heiniche A, Wolf KJ, Muller G, Buhr HJ, Germer CT (2002) Laser induced thermotherapy (LITT) of experimental liver metastases-detection of residual tumors using Gd-DTPA enhanced MRI. Lasers Surg Med 30(4):280–289

    Article  PubMed  Google Scholar 

  17. Möller PH, Lindberg L, Henriksson PH, Persson BR, Tranberg KG (1996) Temperature control and light penetration in a feedback interstitial laser thermotherapy system. Int J Hyperthermia 12:49–63

    PubMed  Google Scholar 

  18. Möller PH, Ivarsson K, Stenram U, Radnell M, Tranberg KG (1997) Interstitial laser thermotherapy of adenocarcinoma transplanted into rat liver. Eur J Surg 163:861–870

    PubMed  Google Scholar 

  19. Sturesson C, Liu DL, Stenram U, Andersson-Engels S (1997) Hepatic inflow occlusion increases the efficacy of interstitial laser-induced thermotherapy in rat. J Surg Res 71:67–72

    Article  PubMed  CAS  Google Scholar 

  20. Tacke J, Mahnken A, Roggan A, Gunther RW (2004) Multipolar radiofrequency ablation: first clinical results. Rofo 176(3):324–329 (Mar)

    PubMed  CAS  Google Scholar 

  21. Vogl TJ, Straub R, Eichler K, Sollner O, Mack MG (2004) Colorectal carcinoma metastases in liver: laser-induced interstitial thermotherapy—local tumor control rate and survival data. Radiology 230(2):450–458 (Feb)

    Article  PubMed  Google Scholar 

  22. Mulier S, Ni Y, Jamart J, Ruers T, Marchal G, Michel L (2005) Local recurrence after hepatic radiofrequency coagulation: multivariate meta-analysis and review of contributing factors. Ann Surg 242(2):158–171 (Aug)

    Article  PubMed  Google Scholar 

  23. Hughes KS, Simon R, Songhorabodi S, Adson MA, Ilstrup DM, Fortner JG, Maclean BJ, Foster JH, Daly JM, Fitzherbert D (1986) Resection of the liver for colorectal carcinoma metastases: a multi-institutional study of patterns of recurrence. Surgery 100(2):278–284

    PubMed  CAS  Google Scholar 

  24. Chiappa A, Zbar AP, Biella F, Staudacher C (1999) Survival after repeat hepatic resection for recurrent colorectal metastases. Hepatogastroenterology 46(26):1065–1070

    PubMed  CAS  Google Scholar 

  25. Yokoyama N, Shirai Y, Ajioka Y, Nagakura S, Suda T, Hatakeyama K (2002) Immunohistochemically detected hepatic micrometastases predict a high risk of intrahepatic recurrence after resection of colorectal carcinoma liver metastases. Cancer 94(6):1642–1647 (Mar 15)

    Article  PubMed  Google Scholar 

  26. Nordlinger B, Guiguet M, Vaillant JC, Balladur P, Boudjema K, Bachellier P, Jaeck D (1996) Surgical resection of colorectal carcinoma metastases to the liver. A prognostic scoring system to improve case selection, based on 1568 patients. Association Francaise de Chirurgie. Cancer 77(7):1254–1262 (Apr 1)

    Article  PubMed  CAS  Google Scholar 

  27. Elias D (1998) Impact of tumor doubling time on the therapeutic strategy: application to so-called synchronous metastases of colorectal cancers. Ann Chir 52(5):413–420

    PubMed  CAS  Google Scholar 

  28. van Dale P, Galand P (1988) Effect of partial hepatectomy on experimental liver invasion by intraportally injected colon carcinoma cells in rats. Invasion Metastasis 8(4):217–227

    PubMed  Google Scholar 

  29. Rashidi B, An Z, Sun FX, Sasson A, Gamagammi R, Moossa AR, Hoffman RM (1999) Minimal liver resection strongly stimulates the growth of human colon cancer in the liver of nude mice. Clin Exp Metastasis 17(6):497–500

    Article  PubMed  CAS  Google Scholar 

  30. Slooter GD, Marquet RL, Jeekel J, Ijzermans JN (1995) Tumour growth stimulation after partial hepatectomy can be reduced by treatment with tumour necrosis factor alpha. Br J Surg 82(1):129–132

    Article  PubMed  CAS  Google Scholar 

  31. Isbert C, Boerner A, Ritz JP, Schuppan D, Buhr HJ, Germer CT (2002) In-situ ablation of experimental liver metastases delays and reduces residual intrahepatic tumour growth and peritoneal tumour spread compared with hepatic resection. Br J Surg 89(10):1252–1259 (Oct)

    Article  PubMed  CAS  Google Scholar 

  32. Isbert C, Ritz JP, Roggan A, Schuppan D, Ruhl M, Buhr HJ, Germer CT (2004) Enhancement of the immune response to residual intrahepatic tumor tissue by laser-induced thermotherapy (LITT) compared to hepatic resection. Lasers Surg Med 35(4):284–292

    Article  PubMed  Google Scholar 

  33. Isbert C, Ritz JP, Roggan A, Schuppan D, Ajubi N, Buhr HJ, Hohenberger W, Germer CT (2006) Laser-induced thermotherapy (LITT) elevates mRNA expression of connective tissue growth factor (CTGF) associated with reduced tumor growth of liver metastases compared to hepatic resection. Lasers Surg Med (in press)

  34. Wissniowski TT, Hansler J, Neureiter D, Frieser M, Schaber S, Esslinger B, Voll R, Strobel D, Hahn EG (2003) Activation of tumor-specific T lymphocytes by radio-frequency ablation of the VX2 hepatoma in rabbits. Cancer Res 63(19):6496–6500 (Oct 1)

    PubMed  CAS  Google Scholar 

  35. Fausto N, Laird AD, Webber EM (1995) Liver regeneration. 2. Role of growth factors and cytokines in hepatic regeneration. FASEB J 9(15):1527–1536

    PubMed  CAS  Google Scholar 

  36. Rudolph KL, Trautwein C, Kubicka S, Rakemann T, Bahr MJ, Sedlaczek N, Schuppan D, Manns MP (1999) Differential regulation of extracellular matrix synthesis during liver regeneration after partial hepatectomy in rats. Hepatology 30(5):1159–1166

    Article  PubMed  CAS  Google Scholar 

  37. Kim TH, Mars WM, Stolz DB, Michalopoulos GK (2000) Expression and activation of pro-MMP-2 and pro-MMP-9 during rat liver regeneration. Hepatology 31(1):75–82

    Article  PubMed  CAS  Google Scholar 

  38. Schuppan D, Ruehl M, Somasundaram R, Hahn EG (2001) Matrix as a modulator of hepatic fibrogenesis. Semin Liver Dis 21(3):351–372

    Article  PubMed  CAS  Google Scholar 

  39. Foda HD, Zucker S (2001) Matrix metalloproteinases in cancer invasion, metastases and angiogenesis. Drug Discov Today 6(9):478–482

    Article  PubMed  CAS  Google Scholar 

  40. Murray GI, Duncan ME, O’Neil P, Melvin WT, Fothergill JE (1996) Matrix Metalloproteinase-1 is associated with poor prognosis in colorectal cancer. Nat Med 2:461–462

    Article  PubMed  CAS  Google Scholar 

  41. Hidalgo M, Eckhardt SG (2001) Development of matrix metalloproteinase inhibitors in cancer therapy. J Natl Cancer Inst 93(3):178–193

    Article  PubMed  CAS  Google Scholar 

  42. Grotendorst GR (1997) Connective tissue growth factor: a mediator of TGF-beta action on fibroblasts. Cytokine Growth Factor Rev 8(3):171–179

    Article  PubMed  CAS  Google Scholar 

  43. Sedlaczek N, Jia JD, Bauer M, Herbst H, Ruehl M, Hahn EG, Schuppan D (2001) Proliferating bile duct epithelial cells are a major source of connective tissue growth factor in rat biliary fibrosis. Am J Pathol 158(4):1239–1244

    PubMed  CAS  Google Scholar 

  44. Scheele J, Altendorf-Hofmann A, Grube T, Hohenberger W, Stangl R, Schmidt K (2001) Resection of colorectal liver metastases. What prognostic factors determine patient selection? (in German) Chirurg 72(5):547–560 (May)

    PubMed  CAS  Google Scholar 

  45. Fong Y, Fortner J, Sun RL, Brennan MF, Blumgart LH (1999) Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. Ann Surg 230(3):309–318 (Sep)

    Article  PubMed  CAS  Google Scholar 

  46. Navarra G, Ayav A, Weber JC, Jensen SL, Smadga C, Nicholls JP, Habib NA, Jiao LR (2005) Short- and-long term results of intraoperative radiofrequency ablation of liver metastases. Int J Colorectal Dis 20(6):521–528 (Nov)

    Article  PubMed  CAS  Google Scholar 

  47. Solbiati L, Livraghi T, Goldberg SN, Ierace T, Meloni F, Dellanoce M, Cova L, Halpern EF, Gazelle GS (2001) Percutaneous radio-frequency ablation of hepatic metastases from colorectal cancer: long-term results in 117 patients. Radiology 221(1):159–166 (Oct)

    Article  PubMed  CAS  Google Scholar 

  48. de Baere T, Elias D, Dromain C, Din MG, Kuoch V, Ducreux M, Boige V, Lassau N, Marteau V, Lasser P, Roche A (2000) Radiofrequency ablation of 100 hepatic metastases with a mean follow-up of more than 1 year. AJR Am J Roentgenol 175(6):1619–1625 (Dec)

    PubMed  Google Scholar 

  49. Oshowo A, Gillams A, Harrison E, Lees WR, Taylor I (2003) Comparison of resection and radiofrequency ablation for treatment of solitary colorectal liver metastases. Br J Surg 90(10):1240–1243

    Article  PubMed  CAS  Google Scholar 

  50. Elias D, Baton O, Sideris L, Matsuhisa T, Pocard M, Lasser P (2004) Local recurrences after intraoperative radiofrequency ablation of liver metastases: a comparative study with anatomic and wedge resections. Ann Surg Oncol 11(5):500–505

    Article  PubMed  Google Scholar 

  51. Pawlik TM, Izzo F, Cohen DS, Morris JS, Curley SA (2003) Combined resection and radiofrequency ablation for advanced hepatic malignancies: results in 172 patients. Ann Surg Oncol 10(9):1059–1069 (Nov)

    Article  PubMed  Google Scholar 

  52. Evrard S, Becouarn Y, Fonck M, Brunet R, Mathoulin-Pelissier S, Picot V (2004) Surgical treatment of liver metastases by radiofrequency ablation, resection, or in combination. Eur J Surg Oncol 30(4):399–406 (May)

    Article  PubMed  CAS  Google Scholar 

  53. Stippel DL, Bohm S, Beckurts KT, Brochhagen HG, Holscher AH (2002) Intraoperative radiofrequency ablation using a 3D navigation tool for treatment of colorectal liver metastases. Onkologie 25(4):346–350 (Aug)

    Article  PubMed  CAS  Google Scholar 

  54. Oshowo A, Gillams AR, Lees WR, Taylor I (2003) Radiofrequency ablation extends the scope of surgery in colorectal liver metastases. Eur J Surg Oncol 29(3):244–247 (Apr)

    Article  PubMed  CAS  Google Scholar 

  55. Vogl TJ, Germer CT, Mack MG (2001) Therapiestudie zu Lebermetastasen des kolorektalen Karzinoms. Dd Ärztebl 98:A839 [Heft 13]

    Google Scholar 

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Acknowledgement

Grants: Deutsche Forschungsgemeinschaft, grant No. GE 932/1-2.

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Authors and Affiliations

  1. Department of General, Visceral and Thoracic Surgery, Klinikum Nuernberg Nord, Prof.-Ernst-Nathan-Str.1, 90419, Nuernberg, Germany

    Christoph Isbert & Christoph-T. Germer

  2. Department of Surgery General, Vascular and Thoracic Surgery, Charité-University Medicine Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany

    Heinz J. Buhr & Joerg-Peter Ritz

  3. Department of Surgery, Friedrich-Alexander-University, Erlangen-Nuernberg, Krankenhausstr. 12, 91054, Erlangen-Nuernberg, Germany

    W. Hohenberger

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  1. Christoph Isbert
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Correspondence to Christoph Isbert.

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Isbert, C., Buhr, H.J., Ritz, JP. et al. Curative in situ ablation of colorectal liver metastases—experimental and clinical implementation. Int J Colorectal Dis 22, 705–715 (2007). https://doi.org/10.1007/s00384-006-0231-5

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