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  • Review Article
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Tumour progression and liver regeneration—insights from animal models

Nature Reviews Gastroenterology & Hepatology volume 10, pages 452–462 (2013)Cite this article

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Abstract

Surgery remains the only curative treatment for colorectal liver metastases. For patients with multiple bilobar spread, extended hepatectomy might be required to achieve complete margin-free resection. In such cases, portal vein occlusion has been developed to induce preoperative hypertrophy of the future remnant liver and increase the resectability rate. Evidence now suggests that liver regeneration after hepatectomy and portal vein occlusion has a protumorigenic role, either through an upregulation of growth factors and cytokines or by haemodynamic changes in the blood supply to the liver. Experimental studies have reported a stimulatory effect of liver regeneration on the tumoral volume of liver metastases and on the metastatic potential of cells engrafted in the liver; this effect seems to depend on the timing of hepatectomy and portal vein occlusion. However, the variability of animal tumour models that are used for research in experimental colorectal liver metastases might account for some of the inconsistent and conflicting results. This Review presents clinical and experimental data pertaining to whether liver regeneration causes proliferation of tumour cells. We also analyse the different animal models of colorectal liver metastases in use and discuss current controversies in the field.

Key Points

  • Clinical data suggest that liver regeneration after partial hepatectomy and portal vein occlusion stimulates the growth of colorectal liver metastases, both in terms of metastatic recurrence and enhanced tumour growth

  • Relevant animal models are necessary to provide information on the pathophysiological mechanisms linking liver regeneration with tumour growth

  • An ideal animal model should be an immunocompetent rodent with established multiple bilobar liver metastases at the time of hepatectomy or portal vein occlusion, which represents the clinical situation faced by surgeons

  • Rodent models have provided reliable evidence that upregulation of circulating growth factors and cytokines, increased arterial blood supply to the liver and angiogenesis have a role in promoting the growth of liver metastases

  • The mechanism linking liver regeneration after portal vein occlusion with tumour growth is complex, and might vary according to the occlusion technique used

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Figure 1: Common and specific mechanisms of liver regeneration affecting tumour progression.
Figure 2: Bilobar colorectal liver metastases in a 72-year-old man showing a tumoral volume increase in both lobes after portal vein embolization.
Figure 3: Theoretical basis for a rat model of colorectal liver metastasis for studying liver-regeneration-associated tumour growth.
Figure 4: Theoretical description of a stepwise model for studying the influence of partial hepatectomy on colorectal liver metastases growth.

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  1. Unité INSERM U965 (Université Paris 7), Angiogénèse et Recherche Translationnelle, Hôpital Lariboisière, 2 Rue Ambroise Paré, Paris, 75010, France

    Chetana Lim & Marc Pocard

  2. Service de Chirurgie Digestive et Hépato-Biliaire et Transplantation Hépatique, Hôpital Henri Mondor, 51 Avenue du Maréchal de Lattre de Tassigney, Créteil, 94010, France

    Daniel Azoulay

  3. Service de Chirurgie Hépato–Bilio–Pancréatique et Transplantation Hépatique, Hôpital Beaujon, 100 Boulevard du Général Leclerc, Clichy, 92110, France

    Francois Cauchy & Olivier Farges

  4. Service de Radiologie, Hôpital Beaujon, 100 Boulevard du Général Leclerc, Clichy, 92110, France

    Maxime Ronot

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C. Lim researched data for the article. C. Lim, F. Cauchy and M. Pocard wrote the article. All of the authors substantially contributed to the discussion of content and reviewed and edited the manuscript before submission.

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Lim, C., Cauchy, F., Azoulay, D. et al. Tumour progression and liver regeneration—insights from animal models. Nat Rev Gastroenterol Hepatol 10, 452–462 (2013). https://doi.org/10.1038/nrgastro.2013.55

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