Breast Cancer-Related Lymphedema: A Review of Management and Innovative Surgical Techniques A Review of Management and Innovative Surgical Techniques
Main Article Content
Lymphedema is one of the most feared complications of breast cancer treatment. The objective of this article is to review the basic workup, staging, and diagnostic criteria for lymphedema and to discuss non-surgical and surgical treatments, with a focus on breast-cancer related lymphedema. Non-surgical treatment consists of intensive physical therapy including manual lymphatic drainage via massage, daily compression wraps, and exercises to prevent scarring and increase mobility. Surgical intervention is considered when non-surgical treatment is ineffective or more recently as a preventive measure. Surgical interventions, used once lymphedema has developed, include 1) lympho-venous bypass, which is the anastomosis of lymphatic vessels distal to the site of dermal backflow to neighboring venules to shunt lymphatic drainage away from the area of lymphatic injury; 2) vascularized lymph node transplant, in which lymph nodes are harvested from a donor site with their supporting artery and vein and transferred to the affected recipient site; and 3) debulking procedures including liposuction and direct excision. Preventive surgical interventions include 1) lymphatic microsurgical preventive healing approach, known as LYMPHA, which also utilizes lympho-venous anastomoses but at the time of lymph node dissection to anastomose lymphatic channels transected during lymph node dissection with adjacent veins to preserve lymphatic drainage of the arm; and 2) axillary reverse mapping, which involves tracer or dye injection within the ipsilateral arm before axillary surgery so that the breast surgeons are able to delineate nodal drainage and therefore attempt to spare nodes specific to arm tissue provided they are not the sentinel lymph node. Patient selection is critical for these procedures, and requires a multi-disciplinary approach.
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
2. Garza R, Skoracki R, Hock K, Povoski SP. A comprehensive overview on the surgical management of secondary lymphedema of the upper and lower extremities related to prior oncologic therapies. BMC Cancer. 2017;17(1):468.
3. Scallan J, Huxley VH, Korthuis RJ. Capillary Fluid Exchange: Regulation, Functions, and Pathology. Colloquium Series on Integrated Systems Physiology: From Molecule to Function. 2010;2(1):1-94.
4. Dayan JH, Ly CL, Kataru RP, Mehrara BJ. Lymphedema: Pathogenesis and Novel Therapies. Annu Rev Med. 2018;69:263-276.
5. Brouillard P, Boon L, Vikkula M. Genetics of lymphatic anomalies. J Clin Invest. 2014;124(3):898-904.
6. Smeltzer DM, Stickler GB, Schirger A. Primary lymphedema in children and adolescents: a follow-up study and review. Pediatrics.
7. Wheeler ES, Chan V, Wassman R, Rimoin DL, Lesavoy MA. Familial lymphedema praecox: Meige’s disease. Plast Reconstr Surg. 1981;67(3):362-364.
8. Kissin MW, Della Rovere GQ, Easton D, Westbury G. Risk of lymphoedema following the treatment of breast cancer. British Journal of Surgery. 1986;73(7):580-584.
9. Laredo J, Lee BB. Lymphedema. In: Mowatt-Larssen E, Desai SS, Dua A, Shortell CEK, eds. Phlebology, Vein Surgery and Ultrasonography: Diagnosis and Management of Venous Disease. Springer International Publishing; 2014:327-339.
10. Gillespie TC, Sayegh HE, Brunelle CL, Daniell KM, Taghian AG. Breast cancer-related lymphedema: risk factors, precautionary measures, and treatments. Gland Surg. 2018;7(4):379-403.
11. DiSipio T, Rye S, Newman B, Hayes S. Incidence of unilateral arm lymphoedema after breast cancer: a systematic review and meta-analysis. Lancet Oncol. 2013;14(6):500-515.
12. Cormier JN, Askew RL, Mungovan KS, Xing Y, Ross MI, Armer JM. Lymphedema beyond breast cancer: a systematic review and meta-analysis of cancer-related secondary lymphedema. Cancer. 2010;116(22):5138-5149.
13. Mehrara BJ, Greene AK. Lymphedema and obesity: is there a link? Plast Reconstr Surg. 2014;134(1):154e-160e.
14. McLaughlin SA, Brunelle CL, Taghian A. Breast Cancer–Related Lymphedema: Risk Factors, Screening, Management, and the Impact of Locoregional Treatment. J Clin Oncol. 2020;38(20):2341-2350.
15. Gowda AU, Nie J, Mets E, Alperovich M, Avraham T. Risk Factors for Lymphedema After Breast Conservation Therapy and Oncoplastic Reduction. Ann Plast Surg. 2021;87(3):248-252.
16. Fish ML, Grover R, Schwarz GS. Quality-of-Life Outcomes in Surgical vs Nonsurgical Treatment of Breast Cancer-Related Lymphedema: A Systematic Review. JAMA Surg. 2020;155(6):513-519.
17. Dupuy A, Benchikhi H, Roujeau JC, et al. Risk factors for erysipelas of the leg (cellulitis): case-control study. BMJ. 1999;318(7198):1591-1594.
18. Grada AA, Phillips TJ. Lymphedema: Pathophysiology and clinical manifestations. Journal of the American Academy of Dermatology. 2017;77(6):1009-1020.
19. Passik SD, McDonald MV. Psychosocial aspects of upper extremity lymphedema in women treated for breast carcinoma. Cancer. 1998;83(S12B):2817-2820.
20. Shih YCT, Xu Y, Cormier JN, et al. Incidence, treatment costs, and complications of lymphedema after breast cancer among women of working age: a 2-year follow-up study. J Clin Oncol. 2009;27(12):2007-2014.
21. Finkelstein ER, Ha M, Hanwright P, et al. A Critical Analysis of American Insurance Coverage for Imaging and Surgical Treatment of Lymphedema. Journal of Vascular Surgery: Venous and Lymphatic Disorders. 2022;0(0).
22. Finkelstein ER, Ha M, Hanwright P, et al. A review of American insurance coverage and criteria for conservative management of lymphedema. Journal of Vascular Surgery: Venous and Lymphatic Disorders. 2022;10(4):929-936.
23. Suami H, Chang DW, Yamada K, Kimata Y. Use of indocyanine green fluorescent lymphography for evaluating dynamic lymphatic status. Plast Reconstr Surg. 2011;127(3):74e-76e.
24. Neligan PC, Kung TA, Maki JH. MR lymphangiography in the treatment of lymphedema. Journal of Surgical Oncology. 2017;115(1):18-22.
25. Maki JH, Neligan PC, Briller N, Mitsumori LM, Wilson GJ. Dark Blood Magnetic Resonance Lymphangiography Using Dual-Agent Relaxivity Contrast (DARC-MRL): A Novel Method Combining Gadolinium and Iron Contrast Agents. Curr Probl Diagn Radiol. 2016;45(3):174-179.
26. Narushima M, Yamamoto T, Ogata F, Yoshimatsu H, Mihara M, Koshima I. Indocyanine Green Lymphography Findings in Limb Lymphedema. J Reconstr Microsurg. 2016;32(1):72-79.
27. Soga S, Onishi F, Mikoshi A, Okuda S, Jinzaki M, Shinmoto H. Lower limb lymphedema staging based on magnetic resonance lymphangiography. Journal of Vascular Surgery: Venous and Lymphatic Disorders. 2022;10(2):445-453.e3.
28. Mikami T, Hosono M, Yabuki Y, et al. Classification of lymphoscintigraphy and relevance to surgical indication for lymphaticovenous anastomosis in upper limb lymphedema. Lymphology. 2011;44(4):155-167.
29. Greene AK, Goss JA. Diagnosis and Staging of Lymphedema. Semin Plast Surg. 2018;32(1):12-16.
30. Kim G, Smith MP, Donohoe KJ, Johnson AR, Singhal D, Tsai LL. MRI staging of upper extremity secondary lymphedema: correlation with clinical measurements. Eur Radiol. 2020;30(8):4686-4694.
31. Schaverien MV, Coroneos CJ. Surgical Treatment of Lymphedema. Plast Reconstr Surg. 2019;144(3):738-758.
32. Földi E. The treatment of lymphedema. Cancer. 1998;83(S12B):2833-2834.
33. Douglass J, Graves P, Gordon S. Self-Care for Management of Secondary Lymphedema: A Systematic Review. PLOS Neglected Tropical Diseases. 2016;10(6):e0004740.
34. Javid SH, Anderson BO. Mounting Evidence Against Complex Decongestive Therapy As a First-Line Treatment for Early Lymphedema. JCO. 2013;31(30):3737-3738.
35. Dayes IS, Whelan TJ, Julian JA, et al. Randomized Trial of Decongestive Lymphatic Therapy for the Treatment of Lymphedema in Women With Breast Cancer. JCO. 2013;31(30):3758-3763.
36. Noh S, Hwang JH, Yoon TH, Chang HJ, Chu IH, Kim JH. Limb Differences in the Therapeutic Effects of Complex Decongestive Therapy on Edema, Quality of Life, and Satisfaction in Lymphedema Patients. Ann Rehabil Med. 2015;39(3):347-359.
37. Oshnari LA, Hosseini SA, Haghighat S, Zadeh SH. The Effect of Complete Decongestive Therapy on Edema Volume Reduction and Pain in Women With Post Breast Surgery Lymph Edema. Int J Cancer Manag. 2016;9(2).
38. Buragadda S, Alhusaini AA, Melam GR, Arora N. Effect of complete decongestive therapy and a home program for patients with post mastectomy lymphedema. Journal of Physical Therapy Science. 2015;27(9):2743-2748.
39. Melam GR, Buragadda S, Alhusaini AA, Arora N. Effect of complete decongestive therapy and home program on health- related quality of life in post mastectomy lymphedema patients. BMC Women’s Health. 2016;16(1):23.
40. Sezgin Ozcan D, Dalyan M, Unsal Delialioglu S, Duzlu U, Polat CS, Koseoglu BF. Complex Decongestive Therapy Enhances Upper Limb Functions in Patients with Breast Cancer-Related Lymphedema. Lymphatic Research and Biology. 2018;16(5):446-452.
41. Sanal-Toprak C, Ozsoy-Unubol T, Bahar-Ozdemir Y, Akyuz G. The efficacy of intermittent pneumatic compression as a substitute for manual lymphatic drainage in complete decongestive therapy in the treatment of breast cancer related lymphedema. Lymphology. 2019;52(2):82-91.
42. Tsai YL, I TJ, Chuang YC, Cheng YY, Lee YC. Extracorporeal Shock Wave Therapy Combined with Complex Decongestive Therapy in Patients with Breast Cancer-Related Lymphedema: A Systemic Review and Meta-Analysis. Journal of Clinical Medicine. 2021;10(24):5970.
43. Park M, Seo KS. Comparison of effectiveness between complex decongestive therapy and stellate ganglion block in breast cancer related lymphedema patients: A prospective randomized study. JCO. 2016;34(15_suppl):e21619-e21619.
44. Gardenier JC, Kataru RP, Hespe GE, et al. Topical tacrolimus for the treatment of secondary lymphedema. Nat Commun. 2017;8(1):14345.
45. Nakamura K, Radhakrishnan K, Wong YM, Rockson SG. Anti-Inflammatory Pharmacotherapy with Ketoprofen Ameliorates Experimental Lymphatic Vascular Insufficiency in Mice. PLOS ONE. 2009;4(12):e8380.
46. Rockson SG, Tian W, Jiang X, et al. Pilot studies demonstrate the potential benefits of antiinflammatory therapy in human lymphedema. JCI Insight. 2018;3(20).
47. O’Brien JG, Chennubhotla SA, Chennubhotla RV. Treatment of edema. Am Fam Physician. 2005;71(11):2111-2117.
48. Gothard L, Cornes P, Earl J, et al. Double-blind placebo-controlled randomised trial of vitamin E and pentoxifylline in patients with chronic arm lymphoedema and fibrosis after surgery and radiotherapy for breast cancer. Radiotherapy and Oncology. 2004;73(2):133-139.
49. Loprinzi CL, Kugler JW, Sloan JA, et al. Lack of Effect of Coumarin in Women with Lymphedema after Treatment for Breast Cancer. New England Journal of Medicine. 1999;340(5):346-350.
50. Pyszel A, Malyszczak K, Pyszel K, Andrzejak R, Szuba A. Disability, psychological distress and quality of life in breast cancer survivors with arm lymphedema. Lymphology. 2006;39(4):185-192.
51. Yamamoto R, Yamamoto T. Effectiveness of the treatment-phase of two-phase complex decongestive physiotherapy for the treatment of extremity lymphedema. Int J Clin Oncol. 2007;12(6):463-468.
52. Pain SJ, Vowler S, Purushotham AD. Axillary vein abnormalities contribute to development of lymphoedema after surgery for breast cancer. British Journal of Surgery. 2005;92(3):311-315.
53. Vandermeeren L, Belgrado JP, Vankerckhove S, et al. Abstract P3-13-28: Lipofilling of the axilla to reduce secondary lymphedema after axillary lymph node dissection. Cancer Research. 2017;77(4_Supplement):P3-13-28.
54. Mihara M, Hara H, Iida T, et al. Antegrade and retrograde lymphatico-venous anastomosis for cancer-related lymphedema with lymphatic valve dysfuction and lymphatic varix. Microsurgery. 2012;32(7):580-584.
55. Lee KT, Park JW, Mun GH. Serial two-year follow-up after lymphaticovenular anastomosis for the treatment of lymphedema. Microsurgery. 2017;37(7):763-770.
56. Ito R, Wu CT, Lin MCY, Cheng MH. Successful treatment of early-stage lower extremity lymphedema with side-to-end lymphovenous anastomosis with indocyanine green lymphography assisted. Microsurgery. 2016;36(4):310-315.
57. Garza RM, Beederman M, Chang DW. Physical and Functional Outcomes of Simultaneous Vascularized Lymph Node Transplant and Lymphovenous Bypass in the Treatment of Lymphedema. Plastic and Reconstructive Surgery. 2022;150(1):169-180.
58. Yang JCS, Wu SC, Chiang MH, Lin WC. Targeting Reflux-Free Veins with a Vein Visualizer to Identify the Ideal Recipient Vein Preoperatively for Optimal Lymphaticovenous Anastomosis in Treating Lymphedema. Plastic and Reconstructive Surgery. 2018;141(3):793-797.
59. Gould DJ, Mehrara BJ, Neligan P, Cheng MH, Patel KM. Lymph node transplantation for the treatment of lymphedema. Journal of Surgical Oncology. 2018;118(5):736-742.
60. Chang DW. Combined Approach to Surgical Treatment of Lymphedema. Lymphat Res Biol. 2021;19(1):23-24.
61. Sosin M, Yin C, Poysophon P, Patel KM. Understanding the Concepts and Physiologic Principles of Lymphatic Microsurgery. J Reconstr Microsurg. 2016;32(8):571-579.
62. Ferguson L. Vascularized Groin Lymph Node Transfer Using the Wrist as a Recipient Site for Management of Postmastectomy Upper Extremity Lymphedema. Plastic and Reconstructive Surgery. https://www.academia.edu/en/27567375/Vascularized_Groin_Lymph_Node_Transfer_Using_the_Wrist_as_a_Recipient_Site_for_Management_of_Postmastectomy_Upper_Extremity_Lymphedema. Published online January 1, 2010. Accessed August 25, 2022.
63. Saaristo AM, Niemi TS, Viitanen TP, Tervala TV, Hartiala P, Suominen EA. Microvascular breast reconstruction and lymph node transfer for postmastectomy lymphedema patients. Ann Surg. 2012;255(3):468-473.
64. Viitanen TP, Mäki MT, Seppänen MP, Suominen EA, Saaristo AM. Donor-site lymphatic function after microvascular lymph node transfer. Plast Reconstr Surg. 2012;130(6):1246-1253.
65. Hamdi M, Ramaut L, De Baerdemaeker R, Zeltzer A. Decreasing donor site morbidity after groin vascularized lymph node transfer with lessons learned from a 12-year experience and review of the literature. J Plast Reconstr Aesthet Surg. 2021;74(3):540-548.
66. Broyles JM, Smith JM, Wong FC, et al. SPECT/CT Reverse Lymphatic Mapping for Groin Vascularized Lymph Node Transplant Planning. Plast Reconstr Surg. Published online August 4, 2022. Accessed August 25, 2022.
67. Scaglioni MF, Arvanitakis M, Chen YC, Giovanoli P, Chia-Shen Yang J, Chang EI. Comprehensive review of vascularized lymph node transfers for lymphedema: Outcomes and complications. Microsurgery. 2018;38(2):222-229.
68. Ward J, King I, Monroy-Iglesias M, et al. A meta-analysis of the efficacy of vascularised lymph node transfer in reducing limb volume and cellulitis episodes in patients with cancer treatment-related lymphoedema. Eur J Cancer. 2021;151:233-244.
69. Schaverien MV, Asaad M, Selber JC, et al. Outcomes of Vascularized Lymph Node Transplantation for Treatment of Lymphedema. J Am Coll Surg. 2021;232(6):982-994.
70. Brorson H. Liposuction in Lymphedema Treatment. J Reconstr Microsurg. 2016;32(01):056-065.
71. Lee D, Piller N, Hoffner M, Manjer J, Brorson H. LIPOSUCTION OF POSTMASTECTOMY ARM LYMPHEDEMA DECREASES THE INCIDENCE OF ERYSIPELAS. Lymphology. 2016;49(2). http://journals.librarypublishing.arizona.edu/lymph/article/id/3826/ Accessed August 25, 2022.
72. Schaverien MV, Munnoch DA, Brorson H. Liposuction Treatment of Lymphedema. Semin Plast Surg. 2018;32(01):042-047.
73. Brorson H, Svensson H, Norrgren K, Thorsson O. LIPOSUCTION REDUCES ARM LYMPHEDEMA WITHOUT SIGNIFICANTLY ALTERING THE ALREADY IMPAIRED LYMPH TRANSPORT. Lymphology. 1998;31(4):156-172.
74. Dumanian GA, Futrell WJ. The Charles Procedure: Misquoted and Misunderstood Since 1950. Plastic and Reconstructive Surgery. 1996;98(7):1258-1263.
75. Boccardo F, Casabona F, De Cian F, et al. Lymphedema Microsurgical Preventive Healing Approach: A New Technique for Primary Prevention of Arm Lymphedema After Mastectomy. Ann Surg Oncol. 2009;16(3):703-708.
76. Herremans KM, Cribbin MP, Riner AN, et al. Five-Year Breast Surgeon Experience in LYMPHA at Time of ALND for Treatment of Clinical T1–4N1–3M0 Breast Cancer. Ann Surg Oncol. 2021;28(10):5775-5787.
77. Coriddi M, Mehrara B, Skoracki R, Singhal D, Dayan JH. Immediate Lymphatic Reconstruction: Technical Points and Literature Review. Plastic and Reconstructive Surgery – Global Open. 2021;9(2):e3431.
78. Ponzone R, Cassina E, Cont NT, Biglia N, Sismondi P. Decreasing arm morbidity by refining axillary surgery in breast cancer. European Journal of Surgical Oncology. 2009;35(4):335-338.
79. Feldman S, Bansil H, Ascherman J, et al. Single Institution Experience with Lymphatic Microsurgical Preventive Healing Approach (LYMPHA) for the Primary Prevention of Lymphedema. Ann Surg Oncol. 2015;22(10):3296-3301.
80. Boccardo F, Casabona F, DeCian F, et al. Lymphatic Microsurgical Preventing Healing Approach (LYMPHA) for primary surgical prevention of breast cancer-related lymphedema: Over 4 years follow-up. Microsurgery. 2014;34(6):421-424.
81. Johnson AR, Kimball S, Epstein S, et al. Lymphedema Incidence After Axillary Lymph Node Dissection: Quantifying the Impact of Radiation and the Lymphatic Microsurgical Preventive Healing Approach. Annals of Plastic Surgery. 2019;82(4S):S234.
82. Ozmen T, Lazaro M, Zhou Y, Vinyard A, Avisar E. Evaluation of Simplified Lymphatic Microsurgical Preventing Healing Approach (S-LYMPHA) for the Prevention of Breast Cancer-Related Clinical Lymphedema After Axillary Lymph Node Dissection. Ann Surg. 2019;270(6):1156-1160.
83. Ochoa D, Korourian S, Boneti C, Adkins L, Badgwell B, Klimberg VS. Axillary reverse mapping: five-year experience. Surgery. 2014;156(5):1261-1268.