Abstract
Background and aims
If temporary inflow occlusion is required during liver resection, the postoperative course might be complicated by ischaemia–reperfusion injury. Steroids protect against ischaemia–reperfusion injury; however, due to its anti-proliferative character concerns exist on its use on liver regeneration after resection. We investigated the effects of methylprednisolone on hepatocyte proliferation after partial hepatectomy with temporary inflow occlusion.
Patients and methods
Prior to surgery, one group of Wistar rats received methylprednisolone, while a second group served as non-treated controls. Ischaemia–reperfusion injury was indicated by AST, ALT, and GLDH at 6 h after surgery. Immunohistochemistry tools were used to determine the mitotic index and Ki-67 expression, while cyclin D1 expression characterized the proliferative activity on days 1, 4, 7, and 10.
Results
The post-ischaemic liver enzyme release had significantly decreased in the methylprednisolone group, while expression of cyclin D1, percentage of Ki-67-positive cells, and mitotic cell index were comparable in both groups. Similar results were found for bilirubin and albumin and for weight of proliferating liver.
Conclusion
Although steroid administration significantly reduced ischaemia–reperfusion-associated tissue injury, it has no apparent effects on hepatic regeneration. Thus, steroids could be recommended if a temporary liver ischaemia is required during surgery, in order to reduce complications caused by severe ischaemia-related organ dysfunction.
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References
Makuuchi M, Takayama T, Gunven P, Kosige T, Yamazaki S, Hasegawa H (1989) Restrictive versus liberal blood transfusion policy for hepatectomies in cirrhotic patients. World J Surg 13:644–648
Kooby DA, Stockman J, Ben-Porat L, Gonen M, Jarnagin WR, Dematteo RP, Tuorto S, Wuest D, Blumgart LH, Fong Y (2003) Influence of transfusions on perioperative and long-term outcome in patients following hepatic resection for colorectal metastases. Ann Surg 237:860–869
Lentsch AB, Kato A, Yoshidome H, McMasters KM, Edwards MJ (2000) Inflammatory mechanisms and therapeutic strategies for warm hepatic ischemia/reperfusion injury. Hepatology 32:169–173
Bilzer M, Gerbes AL (2000) Preservation injury of the liver: mechanisms and novel therapeutic strategies. J Hepatol 32:508–515
Martinez-Mier G, Toledo-Pereyra LH, Ward PA (2000) Adhesion molecules in liver ischemia and reperfusion. J Surg Res 94:185–194
Santiago-Delpin EA, Figueroa I, Lopez R, Vazquez J (1975) Protective effect of steroids on liver ischemia. Am Surg 41:683–695
Shimada M, Saitoh A, Kano T, Takenaka K, Sugimachi K (1996) The effect of perioperative steroid pulse on surgical stress in hepatic resection. Int Surg 81:49–51
Yamashita Y, Shimada M, Hamatsu T, Rikimaru T, Tanaka S, Shirabe K, Sugimachi K (2001) Effects of preoperative steroid administration on surgical stress in hepatic resection. Arch Surg 136:328–333
Wang M, Sakon M, Umeshita K, Okuyama M, Shiozaki K, Nagano H, Dohno K, Nakamori S, Monden M (2001) Prednisolone suppresses ischemia–reperfusion injury of the rat liver by reducing cytokine production and calpain μ activation. J Hepatol 34:278–283
Fujioka T, Murakami M, Niiya T, Aoki T, Murai N, Enami Y, Kusano M (2001) Effect of methylprednisolone on the kinetics of cytokines and liver function of regenerating liver in rats. Hepatol Res 19:60–73
Muratore A, Ribero D, Ferrero A, Bergero R, Capussotti L (2003) Prospective randomized study of steroids in the prevention of ischaemic injury during hepatic resection with pedicle clamping. Br J Surg 90:17–22
Glanemann M, Strenziok R, Kuntze R, Munchow S, Dikopoulos N, Lippek F, Langrehr JM, Dietel M, Neuhaus P, Nussler AK (2004) Ischemic preconditioning and methylprednisolone both equally reduce hepatic ischemia/reperfusion injury. Surgery 135:203–214
Almawi W, Abou Joude MM, Li XC (2002) Transcriptional and post-transcriptional mechanisms of glucocorticoid antiproliferative effects. Hematol Oncol 20:17–32
Nagy P, Kiss A, Schnur J, Thorgeirsson SS (1998) Dexamethasone inhibits the proliferation of hepatocytes and oval cells but not bile duct cells in rat liver. Hepatology 28:423–429
Fausto N (2000) Liver regeneration. J Hepatol 32(S1):19–31
Streetz KL, Luedde T, Manns MP, Trautwein C (2000) Interleukin 6 and liver regeneration. Gut 47:309–312
Magnall D, Bird NC, Majeed AW (2003) The molecular physiology of liver regeneration following partial hepatectomy. Liver 23:124–138
Higgins GM, Anderson RM (1931) Experimental pathology of the liver. I. Restoration of the liver of the white rat following partial surgical removal. Arch Pathol 12:186–202
Gerlach C, Sakkab DY, Scholzen T, Daßler R, Alison MR, Gerdes J (1997) Ki-67 expression during rat liver regeneration after partial hepatectomy. Hepatology 26:573–578
Nussler AK, Liu ZZ, Silvio M, Sweetland MA, Geller DA, Lancaster JR, Billiar TR, Freeswick PD, Lowenstein CL, Simmons RL (1994) Hepatocyte inducible nitric oxide synthesis is influenced in vitro by cell density. Am J Physiol 267:C394–C401
Jung M, Drapier JC, Weidenbach H, Renia L, Oliveira L, Wang A, Beger HG, Nussler AK (2000) Effects of hepatocellular iron imbalance on nitric oxide and reactive oxygen intermediates production in a model of sepsis. J Hepatol 33:387–394
Fornander J, Hellman A, Hasselgren PO (1984) Effects of methylprednisolone on protein synthesis and blood flow in the postischemic liver. Circ Shock 12:287–295
Barnes PJ (1998) Anti-inflammatory actions of glucocorticoids: molecular mechanisms. Clin Sci 94:557–572
Nadal C (1995) Dose-related opposite effects of hydrocortisone on hepatocyte proliferation in the rat. Liver 15:63–69
Kim YI, Salvini P, Auxilia F, Calne RY (1988) Effect of cyclosporine A on hepatocyte proliferation after partial hepatectomy in rats: comparison with standard immunosuppressive agents. Am J Surg 155:245–249
Azzarone A, Francavilla A, Carrieri G, Gasbarrini A, Scotti-Foglieni C, Fagiuoli S, Cillo U, Zeng QH, Starzl TE (1992) Effects of in vivo and in vitro hepatocyte proliferation of methylprednisolone, azathioprine, mycophenolate acid, mizoribine, and prostaglandin E1. Transplant Proc 24:2868–2871
Acknowledgements
We are grateful to Sylvia Albrecht for excellent secretarial help, as well as to Ikonia Rotter for excellent technical and laboratory assistance. Supported in part by Charité Forschungsförderung (2000-676/MG).
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Glanemann, M., Münchow, S., Schirmeier, A. et al. Steroid administration before partial hepatectomy with temporary inflow occlusion does not influence cyclin D1 and Ki-67 related liver regeneration. Langenbecks Arch Surg 389, 380–386 (2004). https://doi.org/10.1007/s00423-004-0507-6
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DOI: https://doi.org/10.1007/s00423-004-0507-6