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Does Lymphovenous Anastomosis Effect Mammalian Target of Rapamycin Inhibitor-associated Lymphedema Patients?

  • Inah Yoon (Department of Plastic and Reconstructive Surgery, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Hyung Bae Kim (Department of Plastic and Reconstructive Surgery, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Jeongmok Cho (Department of Plastic and Reconstructive Surgery, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Changsik John Pak (Department of Plastic and Reconstructive Surgery, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Hyunsuk Peter Suh (Department of Plastic and Reconstructive Surgery, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Jae Yong Jeon (Department of Rehabilitation Medicine, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Joon Pio Hong (Department of Plastic and Reconstructive Surgery, Asan Medical Center, University of Ulsan College of Medicine)
  • Received : 2023.04.02
  • Accepted : 2023.10.23
  • Published : 2024.05.15

Abstract

The mammalian target of rapamycin (mTOR) inhibitors are used to prevent organ transplant rejection and are preferred over other immunosuppressants due to its low nephrotoxicity. However, mTOR inhibitors have been associated with various adverse effects including lymphedema. Although rare in incidence, previously known treatments for mTOR inhibitor-induced lymphedema were limited to discontinuation of related drugs and complex disruptive therapy with variable results. In this article, three patients who developed lymphedema in their lower limbs after using mTOR inhibitors, including two bilateral and one unilateral case, were treated with physiologic surgery methods such as lymphovenous anastomosis (LVA) and lymph node transfer. The efficacy of the treatment was evaluated. In the three cases described, cessation of the drug did not lead to any reduction in edema. The use of LVA and lymph node transfer resulted in early reductions in volume but failed to sustain over time. All patients underwent secondary nonphysiologic surgery such as liposuction resulting in sustained improvement. This series presents the first physiologic approach to mTOR inhibitor-induced lymphedema. Although further study is warranted, the physiologic surgical options may have limited success and nonphysiologic options may offer better sustainable results.

Keywords

References

  1. De Bartolomeis C, Collini A, Rumberger B, et al. Generalized lymphedema in a sirolimus-treated renal transplant patient. Clin Transplant 2008;22(02):254-257 
  2. Kim J, Jeon JY, Ko YM, Kang MS, Park SK, Roh K. Characteristics of lymphedema in patients treated with mammalian target of rapamycin inhibitors. Lymphat Res Biol 2021;19(04):365-371 
  3. Nguyen LS, Vautier M, Allenbach Y, et al. Sirolimus and mTOR inhibitors: a review of side effects and specific management in solid organ transplantation. Drug Saf 2019;42(07):813-825 
  4. Daniell KM, Bardia A, Sun F, et al. Incidence of peripheral edema in patients receiving PI3K/mTOR/CDK4/6 inhibitors for metastatic breast cancer. Breast Cancer Res Treat 2019;175(03):649-658 
  5. Desai N, Heenan S, Mortimer PS. Sirolimus-associated lymphoedema: eight new cases and a proposed mechanism. Br J Dermatol 2009;160(06):1322-1326 
  6. Kerjaschki D. How to control lymphangiogenesis: a novel role for rapamycin. Kidney Int 2007;71(08):717-719 
  7. Huber S, Bruns CJ, Schmid G, et al. Inhibition of the mammalian target of rapamycin impedes lymphangiogenesis. Kidney Int 2007;71(08):771-777 
  8. Ardalan MR. Lymphedema attributed to sirolimus. J Nephropharmacol 2013;2(02):35-36 
  9. Al GainM, Crickx B, Bejar C, et al. [Sirolimus-inducedlymphedema in a kidney-transplant recipient: partial recovery after changeover to tacrolimus]. Ann Dermatol Venereol 2015;142(05):350-355French. 
  10. Fourgeaud C, Simon L, Benoughidane B, Vignes S. Lymphedema in patients treated with sirolimus: 15 cases [in French]. Rev Med Interne 2019;40(03):151-157 
  11. Romagnoli J, Citterio F, Nanni G, Tondolo V, Castagneto M. Severe limb lymphedema in sirolimus-treated patients. Transplant Proc 2005;37(02):834-836 
  12. Chang DW, Masia J, Garza R III, Skoracki R, Neligan PC. Lymphedema: surgical and medical therapy. Plast Reconstr Surg 2016; 138(03):209S-218S 
  13. Kwon JG, Hong DW, Suh HP, Pak CJ, Hong JP. Patient-specific surgical options for breast cancer-related lymphedema: technical tips. Arch Plast Surg 2021;48(03):246-253 
  14. Beederman M, Chang DW. Advances in surgical treatment of lymphedema. Arch Plast Surg 2021;48(06):670-677 
  15. Torio-Padron N, Stark GB, Foldi E, Simunovic F. Treatment of male genital lymphedema: an integrated concept. J Plast Reconstr Aesthet Surg 2015;68(02):262-268 
  16. Czedik-Eysenberg M, Steinbacher J, Obermayer B, et al. Exclusive use of ultrasound for locating optimal LVA sites-a descriptive data analysis. J Surg Oncol 2020;121(01):51-56 
  17. Mohos B, Czedik-Eysenberg M, Steinbacher J, Tinhofer I, Meng S, Tzou CJ. Long-term use of ultrasound for locating optimal LVA sites: a descriptive data analysis. J Reconstr Microsurg 2022;38(03):238-244 
  18. Kim L, Jeon JY, Sung IY, Jeong SY, Do JH, Kim HJ. Prediction of treatment outcome with bioimpedance measurements in breast cancer related lymphedema patients. Ann Rehabil Med 2011;35(05):687-693 
  19. van Heumen S, Riksen JJM, Bramer WM, van Soest G, Vasilic D. Imaging of the lymphatic vessels for surgical planning: a systematic review. Ann Surg Oncol 2023;30(01):462-479 
  20. Oh A, Kajita H, Matoba E, et al. Photoacoustic lymphangiography before and after lymphaticovenular anastomosis. Arch Plast Surg 2021;48(03):323-328