HEPATIC CELL PROLIFERATION PEAKS ONE WEEK AFTER PORTAL VEIN LIGATION AND IS NOT ENHANCED BY INSULIN (EXPERIMENTAL STUDY)

Marta Guimarães; Tiago Morais; Sofia S. Pereira; Ana Monteiro; Ana Vilaça; Tiago Ferreira; Tiago Castro; Pedro Rodrigues; Vera Oliveira; Mário Nora; Artur Águas; Mariana Monteiro; Gil Gonçalves

doi:10.34635/rpc.576

Marta Guimarães Dep of General Surgery, Centro Hospitalar de Entre o Douro e Vouga; Centro Experimental de Cirurgia Avançada, Vila do Conde, Portugal; Dep of Anatomy, Multidisciplinary Unit for Biomedical Research (UMIB), ICBAS, University of Porto http://orcid.org/0000-0001-8094-7197
Tiago Morais Dep of Anatomy, Multidisciplinary Unit for Biomedical Research (UMIB), ICBAS, University of Porto http://orcid.org/0000-0003-4905-706X
Sofia S. Pereira Dep of Anatomy, Multidisciplinary Unit for Biomedical Research (UMIB), ICBAS, University of Porto http://orcid.org/0000-0001-6947-4560
Ana Monteiro Escola Superior de Tecnologia da Saúde do Porto
Ana Vilaça João Carlos Costa, Diagnóstico por Imagem, Gondomar, Portugal
Tiago Ferreira Dep of General Surgery, Centro Hospitalar de Entre o Douro e Vouga; Centro Experimental de Cirurgia Avançada, Vila do Conde, Portugal
Tiago Castro Dep of General Surgery, Centro Hospitalar de Entre o Douro e Vouga; Centro Experimental de Cirurgia Avançada, Vila do Conde, Portugal http://orcid.org/0000-0002-8534-558X
Pedro Rodrigues Dep of General Surgery, Centro Hospitalar de Entre o Douro e Vouga; Centro Experimental de Cirurgia Avançada, Vila do Conde, Portugal
Vera Oliveira Dep of General Surgery, Centro Hospitalar de Entre o Douro e Vouga; Centro Experimental de Cirurgia Avançada, Vila do Conde, Portugal
Mário Nora Dep of General Surgery, Centro Hospitalar de Entre o Douro e Vouga; Centro Experimental de Cirurgia Avançada, Vila do Conde, Portugal
Artur Águas Dep of Anatomy, Multidisciplinary Unit for Biomedical Research (UMIB), ICBAS, University of Porto http://orcid.org/0000-0002-1487-9517
Mariana Monteiro Dep of Anatomy, Multidisciplinary Unit for Biomedical Research (UMIB), ICBAS, University of Porto http://orcid.org/0000-0002-0662-1831
Gil Gonçalves Dep of General Surgery, Centro Hospitalar de Entre o Douro e Vouga

Abstract

Introduction: Selective portal vein ligation is currently used to induce hypertrophy of healthy liver segments before partial hepatectomy performed to treat metastatic or primary liver cancer. A major limitation of this procedure is the time interval needed between the portal ligation and hepatic resection, potentially leading to tumour progression. We report the characterization of the liver regeneration kinetics after portal ligation on a rat model, also testing the usefulness of insulin to accelerate liver hypertrophy after the procedure.

Materials and Methods: Liver function and morphology in male Wistar rats was evaluated 1, 2 or 4 weeks after portal ligation alone or with concomitant continuous intraperitoneal insulin infusion and compared to those of intact controls.

Results: Selective portal vein ligation induced ipsilateral lobe atrophy and contralateral lobe hypertrophy. In this model, liver lobe hypertrophy reached its peak at 1 week after portal ligation (PVL:0,13cm; PVL+Insulin:0,34cm) and insulin infusion had no significant additional effect on the liver response to portal ligation.

Discussion and conclusion: Hepatocyte proliferation after selective portal ligation was a fast phenomenon, peaking as early as 1 week after the procedure. Insulin was not useful as adjuvant therapy to further increase hepatocyte proliferation after portal ligation in the rat.

Downloads

Download data is not yet available.

References

1. Clavien, P.A., et al., Strategies for safer liver surgery and partial liver transplantation. N Engl J Med, 2007. 356(15): p. 1545-59.

2. Elias, D., et al., Strategies for resection using portal vein embolization: metastatic liver cancer. Semin Intervent Radiol, 2008. 25(2): p. 123-31.

3. Lainas, P., et al., Liver regeneration and recanalization time course following reversible portal vein embolization. J Hepatol, 2008. 49(3): p. 354-62.

4. Breitenstein, S., et al., “State of the art” in liver resection and living donor liver transplantation: a worldwide survey of 100 liver centers. World J Surg, 2009. 33(4): p. 797-803.

5. Tseng, J.H., et al., Significance of insulin signaling in liver regeneration triggered by portal vein ligation. J Surg Res, 2011. 166(1): p. 77-86.

6. Kasai, Y., et al., Prediction of the remnant liver hypertrophy ratio after preoperative portal vein embolization. Eur Surg Res, 2013. 51(3-4): p. 129-37.

7. May, B.J. and D.C. Madoff, Portal vein embolization: rationale, technique, and current application. Semin Intervent Radiol, 2012. 29(2): p. 81-9.

8. Ebata, T., et al., Portal vein embolization before extended hepatectomy for biliary cancer: current technique and review of 494 consecutive embolizations. Dig Surg, 2012. 29(1): p. 23-9.

9. Moris, D., et al., Mechanistic insights of rapid liver regeneration after associating liver partition and portal vein ligation for stage hepatectomy. World J Gastroenterol, 2016. 22(33): p. 7613-24.

10. Fausto, N., Liver regeneration. J Hepatol, 2000. 32(1 Suppl): p. 19-31.

11. Trotter, N.L., Electron-opaque, lipid-containing bodies in mouse liver at early intervals after partial hepatectomy and sham operation. J Cell Biol, 1965. 25(3): p. Suppl:41-52.

12. Leveille, G.A. and K. Chakrabarty, Diurnal variations in tissue glycogen and liver weight of meal-fed rats. J Nutr, 1967. 93(4): p. 546-54.

13. Tralhao, J.G., et al., Hepatectomy and liver regeneration: from experimental research to clinical application. ANZ J Surg, 2014. 84(9): p. 665-71.

14. Backes, A.N., et al., Effects of tacrolimus and insulin in a liver regeneration model in growing animals with portal vein stenosis: immunohistochemical and molecular studies. Pediatr Surg Int, 2014. 30(4): p. 423-9.

15. Francavilla, A., et al., Discordance between glucokinase activity and insulin and glucagon receptor changes occurring during liver regeneration in the rat. Horm Metab Res, 1984. 16 Suppl 1: p. 47-50.

16. Starzl, T.E., K.A. Porter, and C.W. Putnam, Intraportal insulin protects from the liver injury of portacaval shunt in dogs. Lancet, 1975. 2(7947): p. 1241-2.

17. Aoki, T., et al., Sequential preoperative arterial and portal venous embolizations in patients with hepatocellular carcinoma. Arch Surg, 2004. 139(7): p. 766-74.

18. Nagino, M., et al., Changes in hepatic lobe volume in biliary tract cancer patients after right portal vein embolization. Hepatology, 1995. 21(2): p. 434-9.

19. Freise, J., W.H. Mueller, and C.E. Broelsch, Accumulation of insulin and glucagon in the liver (via portal vein catheter or with liposomes) does not stimulate liver cell regeneration after partial hepatectomy in normal or portocaval shunted rats. Res Exp Med (Berl), 1982. 180(1): p. 31-9.

20. Abu Rmilah, A.A., W. Zhou, and S.L. Nyberg, Hormonal Contribution to Liver Regeneration. Mayo Clin Proc Innov Qual Outcomes, 2020. 4(3): p. 315-338.

21. Gilgenkrantz, H. and A. Collin de l’Hortet, Understanding Liver Regeneration: From Mechanisms to Regenerative Medicine. Am J Pathol, 2018. 188(6): p. 1316 1327.

22. Loffroy, R., et al., Preoperative portal vein embolization in liver cancer: indications, techniques and outcomes. Quant Imaging Med Surg, 2015. 5(5): p. 730-9.

23. Jungermann, K. and T. Kietzmann, Oxygen: modulator of metabolic zonation and disease of the liver. Hepatology, 2000. 31(2): p. 255-60.

24. Liska, V., et al., Interleukin-6 augments activation of liver regeneration in porcine model of partial portal vein ligation. Anticancer Res, 2009. 29(6): p. 2371-7.

25. Santos, N.P., A.A. Colaco, and P.A. Oliveira, Animal models as a tool in hepatocellular carcinoma research: A Review. Tumour Biol, 2017. 39(3): p. 1010428317695923.