Abstract
Introduction
Mammalian target rapamycin inhibitors (m-TORi) are increasingly used in patients undergoing liver transplantation (LT). Yet, there is rising concern that they also could impair wound healing and favor the development of several surgical complications. This report was designed to evaluate both feasibility and safety of major surgery in liver transplant recipients receiving m-TORi–based immunosuppression without therapeutic discontinuation.
Methods
From 2007 to 2012, six liver transplant recipients underwent nine major abdominal or thoracic surgical procedures without m-TORi discontinuation or specific dosage adjustment. Their characteristics and postoperative outcomes were retrospectively analyzed.
Results
Indications for m-TORi were de novo or recurrent malignant disease in five patients and calcineurin inhibitors related neurologic toxicity in one patient. Abdominal procedures, thoracic procedures, and combined thoracic and abdominal procedures were performed in six, two, and one cases respectively. Emergency surgery was performed in one case and elective procedures were performed in eight cases, including five for malignant disease and three for late surgical complications following LT. No patient died postoperatively. One major complication was observed, but no patient required reoperation. No evisceration, incisional surgical site infection, or lymphocele occurred.
Conclusions
Major surgery in liver transplant recipients receiving m-TOR inhibitors appears both feasible and safe without therapeutic discontinuation or specific dosage adjustment.
References
Ekberg H, Tedesco-Silva H, Demirbas A et al (2007) Reduced exposure to calcineurin inhibitors in renal transplantation. N Engl J Med 357:2562–2575
Naesens M, Kuypers DR, Sarwal M (2009) Calcineurin inhibitor nephrotoxicity. Clin J Am Soc Nephrol 4:481–508
Wijdicks EF (2001) Neurotoxicity of immunosuppressive drugs. Liver Transpl 7:937–942
Chandok N, Watt KD (2012) Burden of de novo malignancy in the liver transplant recipient. Liver Transpl 18:277–1289
Fung J, Kelly D, Kadry Z et al (2005) Immunosuppression in liver transplantation: beyond calcineurin inhibitors. Liver Transpl 11:267–280
Laplante M, Sabatini DM (2012) mTOR signaling in growth control and disease. Cell 149:274–293
Foster KG, Fingar DC (2010) Mammalian target of rapamycin (mTOR): conducting the cellular signaling symphony. J Biol Chem 285:14071–14077
Kawahara T, Asthana S, Kneteman NM (2011) m-TOR inhibitors: What role in liver transplantation? J Hepatol 55:1441–1451
Sanchez Antolin G, Garcia Pajares F, Lorenzo Pelayo S et al (2011) Indications and effectiveness of the mammalian target of rapamycin in liver transplantation. Transpl Proc 43:714–717
Wagner D, Kniepeiss D, Schaffellner S et al (2010) Sirolimus has a potential to influent viral recurrence in HCV positive liver transplant candidates. Int Immunopharmacol 10:990–993
Nashan B, Citterio F (2012) Wound healing complications and the use of mammalian target of rapamycin inhibitors in kidney transplantation: a critical review of the literature. Transplantation 94:547–561
Pengel LH, Liu LQ, Morris PJ (2011) Do wound complications or lymphoceles occur more often in solid organ transplant recipients on mTOR inhibitors? A systematic review of randomized controlled trials. Transpl Int 24:1216–1230
Dindo D, Demartines N, Clavien PA (2004) Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 240:205–213
Humar R, Kiefer FN, Berns H et al (2002) Hypoxia enhances vascular cell proliferation and angiogenesis in vitro via rapamycin (mTOR)-dependent signaling. FASEB J 16:771–780
Willems MC, Hendriks T, De Man BM et al (2011) Everolimus-induced loss of wound strength can be prevented by a short postoperative delay in its administration. Wound Repair Regen 19:680–686
Van Der Vliet JA, Willems MC, De Man BM et al (2006) Everolimus interferes with healing of experimental intestinal anastomoses. Transplantation 82:1477–1483
Kuppahally S, Al-Khaldi A, Weisshaar D et al (2006) Wound healing complications with de novo sirolimus versus mycophenolate mofetil-based regimen in cardiac transplant recipients. Am J Transpl 6:986–992
Dean PG, Lund WJ, Larson TS et al (2004) Wound-healing complications after kidney transplantation: a prospective, randomized comparison of sirolimus and tacrolimus. Transplantation 77:1555–1561
Tondolo V, Citterio F, Massa A et al (2006) Lymphocele after renal transplantation: the influence of the immunosuppressive therapy. Transpl Proc 38:1051–1052
Kahn D, Spearman CW, Mall A et al (2005) Effect of rapamycin on the healing of the bile duct. Transplant Proc 37:832–833
Deoliveira ML, Jassem W, Valente R et al (2011) Biliary complications after liver transplantation using grafts from donors after cardiac death: results from a matched control study in a single large volume center. Ann Surg 254:716–722; discussion 722–713
Blachar A, Federle MP (2001) Bowel obstruction following liver transplantation: clinical and ct findings in 48 cases with emphasis on internal hernia. Radiology 218:384–388
Vardanian AJ, Farmer DG, Ghobrial RM et al (2006) Incisional hernia after liver transplantation. J Am Coll Surg 203:421–425
Mazzaferro V, Llovet JM, Miceli R et al (2009) Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. Lancet Oncol 10:35–43
Hall EC, Pfeiffer RM, Segev DL et al (2013) Cumulative incidence of cancer after solid organ transplantation. Cancer 119:2300–2308
Elfadawy N, Flechner SM, Liu X et al (2013) The impact of surveillance and rapid reduction in immunosuppression to control BK virus-related graft injury in kidney transplantation. Transpl Int 26:822–832
Ciancio G, Burke GW, Gaynor JJ et al (2004) A randomized long-term trial of tacrolimus and sirolimus versus tacrolimus and mycophenolate mofetil versus cyclosporine (NEORAL) and sirolimus in renal transplantation. I. Drug interactions and rejection at one year. Transplantation 77:244–251
Kandaswamy R, Melancon JK, Dunn T et al (2005) A prospective randomized trial of steroid-free maintenance regimens in kidney transplant recipients—an interim analysis. Am J Transpl 5:1529–1536
Buchler M, Caillard S, Barbier S et al (2007) Sirolimus versus cyclosporine in kidney recipients receiving thymoglobulin, mycophenolate mofetil and a 6-month course of steroids. Am J Transpl 7:2522–2531
Kirchner GI, Meier-Wiedenbach I, Manns MP (2004) Clinical pharmacokinetics of everolimus. Clin Pharmacokinet 43:83–95
Valente JF, Hricik D, Weigel K et al (2003) Comparison of sirolimus vs. mycophenolate mofetil on surgical complications and wound healing in adult kidney transplantation. Am J Transpl 3:1128–1134
Fikatas P, Schoening W, Lee JE et al (2013) Incidence, risk factors and management of incisional hernia in a high volume liver transplant center. Ann Transpl 18:223–230
Dunkelberg JC, Trotter JF, Wachs M et al (2003) Sirolimus as primary immunosuppression in liver transplantation is not associated with hepatic artery or wound complications. Liver Transpl 9:463–468
Conflict of interest
All authors declare that they have no conflicts of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Schwarz, L., Cauchy, F., Conti, F. et al. Preliminary Report of Major Surgery in Liver Transplant Recipients Receiving m-TOR Inhibitors without Therapeutic Discontinuation. World J Surg 38, 3193–3198 (2014). https://doi.org/10.1007/s00268-014-2693-x
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00268-014-2693-x