Research progress of vascularized lymph node transfer for extremity lymphedema_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

QIAN Youlei , YANG Kai ,  MU Lan

Department of Plastic & Medical Aesthetic Surgery, Peking University People’s Hospital, Beijing, 100034, P.R.China;

Corresponding author：

MU Lan, Email: mulan666@aliyun.com

Keywords：

Lymphedema; vascularized lymph node transfer; animal experiment; clinical trial

DOI：

10.7507/1002-1892.201801069

Video：

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Objective To review the current progress of clinical and experimental research of vascularized lymph node transfer for lymphedema. Methods The domestic and abroad literature about vascularized lymph node transfer in treatment of lymphedema was reviewed and analyzed. Results Experimental studies in animal model indicate that vascularized lymph node transfer can improve lymph node survival and show a promising effectiveness in reducing lymphedema. " Lymphatic wick” and " lymph pump” were the two main hypotheses proposed to explain the potential functional mechanism of vascularized lymph node transfer in treatment of lymphedema. Improvement in lymphedema symptoms are reported in most of the clinical trials, but the level of evidence to advocate this procedure in the treatment of lymphedema remains low because of the small number of the cases and problems in their methodologies. Conclusion Based on current evidence, vascularized lymph node transfer seems to be a promising treatment for lymphedema, but long-term well-designed studies are required to further explore the effectiveness of this procedure.

Citation： QIAN Youlei, YANG Kai, MU Lan. Research progress of vascularized lymph node transfer for extremity lymphedema. Chinese Journal of Reparative and Reconstructive Surgery, 2018, 32(8): 979-983. doi: 10.7507/1002-1892.201801069 Copy

1.	Rockson SG. The unique biology of lymphatic edema. Lymphat Res Biol, 2009, 7(2): 97-100.
2.	Jaffe HL, Richter MN. The regeneration of autoplastic lymph node transplants. J Exp Med, 1928, 47(6): 977-980.
3.	Blum KS, Hadamitzky C, Gratz KF, et al. Effects of autotrans-planted lymph node fragments on the lymphatic system in the pig model. Breast Cancer Res Treat, 2010, 120(1): 59-66.
4.	Fu K, Izquierdo R, Vandevender D, et al. Transplantation of lymph node fragments in a rabbit ear lymphedema model: a new method for restoring the lymphatic pathway. Plast Reconstr Surg, 1998, 101(1): 134-141.
5.	Pabst R, Rothkötter HJ. Regeneration of autotransplanted lymph node fragments. Cell Tissue Res, 1988, 251(3): 597-601.
6.	Piller NB, Clodius L. Lymphoedema of the rabbit ear following partial and complete lymphatic blockade; its effects on fibrotic development, enzyme types and their activity levels. Br J Exp Pathol, 1978, 59(3): 319-326.
7.	Shesol BF, Nakashima R, Alavi A, et al. Successful lymph node transplantation in rats, with restoration of lymphatic function. Plast Reconstr Surg, 1979, 63(6): 817-823.
8.	Chen HC, O’Brien BM, Rogers IW, et al. Lymph node transfer for the treatment of obstructive lymphoedema in the canine model. Br J Plast Surg, 1990, 43(5): 578-586.
9.	Tobbia D, Semple J, Baker A, et al. Experimental assessment of autologous lymph node transplantation as treatment of postsurgical lymphedema. Plast Reconstr Surg, 2009, 124(3): 777-786.
10.	Jeltsch M, Kaipainen A, Joukov V, et al. Hyperplasia of lymphatic vessels in VEGF-C transgenic mice. Science, 1997, 276(5317): 1423-1425.
11.	Honkonen KM, Visuri MT, Tervala TV, et al. Lymph node transfer and perinodal lymphatic growth factor treatment for lymphedema. Ann Surg, 2013, 257(5): 961-967.
12.	Lähteenvuo M, Honkonen K, Tervala T, et al. Growth factor therapy and autologous lymph node transfer in lymphedema. Circulation, 2011,123(6): 613-620.
13.	Takeda K, Sowa Y, Nishino K, et al. Adipose-derived stem cells promote proliferation, migration, and tube formation of lymphatic endothelial cells in vitro by secreting lymphangiogenic factors. Ann Plast Surg, 2015, 74(6): 728-736.
14.	Hayashida K, Yoshida S, Yoshimoto H, et al. Adipose-derived stem cells and vascularized lymph node transfers successfully treat mouse hindlimb secondary lymphedema by early reconnection of the lymphatic system and lymphangiogenesis. Plast Reconstr Surg, 2017, 139(3): 639-651.
15.	Skobe M, Hawighorst T, Jackson DG, et al. Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis. Nat Med, 2001, 7(2): 192-198.
16.	Suami H, Scaglioni MF, Dixon KA, et al. Interaction between vascularized lymph node transfer and recipient lymphatics after lymph node dissection-a pilot study in a canine model. J Surg Res, 2016, 204(2): 418-427.
17.	Tourani SS, Taylor GI, Ashton MW. Vascularized lymph node transfer: A review of the current evidence. Plast Reconstr Surg, 2016,137(3): 985-993.
18.	Aschen SZ, Farias-Eisner G, Cuzzone DA, et al. Lymph node transplantation results in spontaneous lymphatic reconnection and restoration of lymphatic flow. Plast Reconstr Surg, 2014,133(2): 301-310.
19.	Cheng MH, Chen SC, Henry SL, et al. Vascularized groin lymph node flap transfer for postmastectomy upper limb lymphedema: flap anatomy, recipient sites, and outcomes. Plast Reconstr Surg, 2013,131(6): 1286-1298.
20.	Cheng MH, Huang JJ, Nguyen DH, et al. A novel approach to the treatment of lower extremity lymphedema by transferring a vascularized submental lymph node flap to the ankle. Gynecol Oncol, 2012,126(1): 93-98.
21.	Lin CH, Ali R, Chen SC, et al. Vascularized groin lymph node transfer using the wrist as a recipient site for management of postmastectomy upper extremity lymphedema. Plast Reconstr Surg, 2009, 123(4): 1265-1275.
22.	Ito R, Zelken J, Yang CY, et al. Proposed pathway and mechanism of vascularized lymph node flaps. Gynecol Oncol, 2016,141(1): 182-188.
23.	Clodius L, Smith PJ, Bruna J, et al. The lymphatics of the groin flap. Ann Plast Surg, 1982, 9(6): 447-458.
24.	Becker C, Assouad J, Riquet M, et al. Postmastectomy lymphedema: long-term results following microsurgical lymph node transplantation. Ann Surg, 2006, 243(3): 313-315.
25.	Chen R, Mu L, Zhang H, et al. Simultaneous breast reconstruction and treatment of breast cancer-related upper arm lymphedema with lymphatic lower abdominal flap. Ann Plast Surg, 2014, 73 Suppl 1: S12-17.
26.	Zhang H, Chen W, Mu L, et al. The distribution of lymph nodes and their nutrient vessels in the groin region: an anatomic study for design of the lymph node flap. Microsurgery, 2014, 34(7): 558-561.
27.	穆兰花, 张寒, 陈茹, 等. 乳房再造和胸壁修复同时应用血管化的淋巴移植修复治疗乳腺癌术后上肢淋巴水肿. 临床肿瘤学杂志, 2013, 18(1): 54-56.
28.	穆籣, 毕晔, 彭喆, 等. 自体组织乳房再造及胸壁修复同期行吻合血管淋巴结组织移植及淋巴管静脉吻合治疗乳腺癌术后腋窝凹陷畸形及上肢淋巴水肿. 中华整形外科杂志, 2017, 33(增刊): 54-60.
29.	穆籣. 乳房再造同期上肢淋巴水肿治疗和预防的现状及趋势. 中华整形外科杂志, 2018, 34(4): 247-251.
30.	Saaristo AM, Niemi TS, Viitanen TP, et al. Microvascular breast reconstruction and lymph node transfer for postmastectomy lymphedema patients. Ann Surg, 2012, 255(3): 468-473.
31.	Nguyen AT, Chang EI, Suami H, et al. An algorithmic approach to simultaneous vascularized lymph node transfer with microvascular breast reconstruction. Ann Surg Oncol, 2015, 22(9): 2919-2924.
32.	Ciudad P, Date S, Manrique OJ, et al. Recurrent advanced lower extremity lymphedema following initial successful vascularized lymph node transfer: A clinical and histopathological analysis. Arch Plast Surg, 2017,44(1): 87-89.
33.	Scaglioni MF, Suami H. Lymphatic anatomy of the inguinal region in aid of vascularized lymph node flap harvesting. J Plast Reconstr Aesthet Surg, 2015, 68(3): 419-427.
34.	Tourani SS, Taylor GI, Ashton MW. Anatomy of the superficial lymphatics of the abdominal wall and the upper thigh and its implications in lymphatic microsurgery. J Plast Reconstr Aesthet Surg, 2013, 66(10): 1390-1395.
35.	Vignes S, Blanchard M, Yannoutsos A, et al. Complications of autologous lymph-node transplantation for limb lymphoedema. Eur J Vasc Endovasc Surg, 2013, 45(5): 516-520.
36.	Sulo E, Hartiala P, Viitanen T, et al. Risk of donor-site lymphatic vessel dysfunction after microvascular lymph node transfer. J Plast Reconstr Aesthet Surg, 2015, 68(4): 551-558.
37.	Dayan JH, Dayan E, Smith ML. Reverse lymphatic mapping: a new technique for maximizing safety in vascularized lymph node transfer. Plast Reconstr Surg, 2015, 135(1): 277-285.
38.	Finegold DN, Baty CJ, Knickelbein KZ, et al. Connexin 47 mutations increase risk for secondary lymphedema following breast cancer treatment. Clin Cancer Res, 2012, 18(8): 2382-2390.
39.	Poccia I, Lin CY, Cheng MH. Platysma-sparing vascularized submental lymph node flap transfer for extremity lymphedema. J Surg Oncol, 2017, 115(1): 48-53.
40.	Chang DW. Lymphaticovenular bypass for lymphedema management in breast cancer patients: a prospective study. Plast Reconstr Surg, 2010,126(3): 752-758.
41.	O’Brien BM, Hickey MJ, Hurley JV, et al. Microsurgical transfer of the greater omentum in the treatment of canine obstructive lymphoedema. Br J Plast Surg, 1990, 43(4): 440-446.
42.	Nguyen AT, Suami H, Hanasono MM, et al. Long-term outcomes of the minimally invasive free vascularized omental lymphatic flap for the treatment of lymphedema. J Surg Oncol, 2017, 115(1): 84-89.

1. Rockson SG. The unique biology of lymphatic edema. Lymphat Res Biol, 2009, 7(2): 97-100.
2. Jaffe HL, Richter MN. The regeneration of autoplastic lymph node transplants. J Exp Med, 1928, 47(6): 977-980.
3. Blum KS, Hadamitzky C, Gratz KF, et al. Effects of autotrans-planted lymph node fragments on the lymphatic system in the pig model. Breast Cancer Res Treat, 2010, 120(1): 59-66.
4. Fu K, Izquierdo R, Vandevender D, et al. Transplantation of lymph node fragments in a rabbit ear lymphedema model: a new method for restoring the lymphatic pathway. Plast Reconstr Surg, 1998, 101(1): 134-141.
5. Pabst R, Rothkötter HJ. Regeneration of autotransplanted lymph node fragments. Cell Tissue Res, 1988, 251(3): 597-601.
6. Piller NB, Clodius L. Lymphoedema of the rabbit ear following partial and complete lymphatic blockade; its effects on fibrotic development, enzyme types and their activity levels. Br J Exp Pathol, 1978, 59(3): 319-326.
7. Shesol BF, Nakashima R, Alavi A, et al. Successful lymph node transplantation in rats, with restoration of lymphatic function. Plast Reconstr Surg, 1979, 63(6): 817-823.
8. Chen HC, O’Brien BM, Rogers IW, et al. Lymph node transfer for the treatment of obstructive lymphoedema in the canine model. Br J Plast Surg, 1990, 43(5): 578-586.
9. Tobbia D, Semple J, Baker A, et al. Experimental assessment of autologous lymph node transplantation as treatment of postsurgical lymphedema. Plast Reconstr Surg, 2009, 124(3): 777-786.
10. Jeltsch M, Kaipainen A, Joukov V, et al. Hyperplasia of lymphatic vessels in VEGF-C transgenic mice. Science, 1997, 276(5317): 1423-1425.
11. Honkonen KM, Visuri MT, Tervala TV, et al. Lymph node transfer and perinodal lymphatic growth factor treatment for lymphedema. Ann Surg, 2013, 257(5): 961-967.
12. Lähteenvuo M, Honkonen K, Tervala T, et al. Growth factor therapy and autologous lymph node transfer in lymphedema. Circulation, 2011,123(6): 613-620.
13. Takeda K, Sowa Y, Nishino K, et al. Adipose-derived stem cells promote proliferation, migration, and tube formation of lymphatic endothelial cells in vitro by secreting lymphangiogenic factors. Ann Plast Surg, 2015, 74(6): 728-736.
14. Hayashida K, Yoshida S, Yoshimoto H, et al. Adipose-derived stem cells and vascularized lymph node transfers successfully treat mouse hindlimb secondary lymphedema by early reconnection of the lymphatic system and lymphangiogenesis. Plast Reconstr Surg, 2017, 139(3): 639-651.
15. Skobe M, Hawighorst T, Jackson DG, et al. Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis. Nat Med, 2001, 7(2): 192-198.
16. Suami H, Scaglioni MF, Dixon KA, et al. Interaction between vascularized lymph node transfer and recipient lymphatics after lymph node dissection-a pilot study in a canine model. J Surg Res, 2016, 204(2): 418-427.
17. Tourani SS, Taylor GI, Ashton MW. Vascularized lymph node transfer: A review of the current evidence. Plast Reconstr Surg, 2016,137(3): 985-993.
18. Aschen SZ, Farias-Eisner G, Cuzzone DA, et al. Lymph node transplantation results in spontaneous lymphatic reconnection and restoration of lymphatic flow. Plast Reconstr Surg, 2014,133(2): 301-310.
19. Cheng MH, Chen SC, Henry SL, et al. Vascularized groin lymph node flap transfer for postmastectomy upper limb lymphedema: flap anatomy, recipient sites, and outcomes. Plast Reconstr Surg, 2013,131(6): 1286-1298.
20. Cheng MH, Huang JJ, Nguyen DH, et al. A novel approach to the treatment of lower extremity lymphedema by transferring a vascularized submental lymph node flap to the ankle. Gynecol Oncol, 2012,126(1): 93-98.
21. Lin CH, Ali R, Chen SC, et al. Vascularized groin lymph node transfer using the wrist as a recipient site for management of postmastectomy upper extremity lymphedema. Plast Reconstr Surg, 2009, 123(4): 1265-1275.
22. Ito R, Zelken J, Yang CY, et al. Proposed pathway and mechanism of vascularized lymph node flaps. Gynecol Oncol, 2016,141(1): 182-188.
23. Clodius L, Smith PJ, Bruna J, et al. The lymphatics of the groin flap. Ann Plast Surg, 1982, 9(6): 447-458.
24. Becker C, Assouad J, Riquet M, et al. Postmastectomy lymphedema: long-term results following microsurgical lymph node transplantation. Ann Surg, 2006, 243(3): 313-315.
25. Chen R, Mu L, Zhang H, et al. Simultaneous breast reconstruction and treatment of breast cancer-related upper arm lymphedema with lymphatic lower abdominal flap. Ann Plast Surg, 2014, 73 Suppl 1: S12-17.
26. Zhang H, Chen W, Mu L, et al. The distribution of lymph nodes and their nutrient vessels in the groin region: an anatomic study for design of the lymph node flap. Microsurgery, 2014, 34(7): 558-561.
27. 穆兰花, 张寒, 陈茹, 等. 乳房再造和胸壁修复同时应用血管化的淋巴移植修复治疗乳腺癌术后上肢淋巴水肿. 临床肿瘤学杂志, 2013, 18(1): 54-56.
28. 穆籣, 毕晔, 彭喆, 等. 自体组织乳房再造及胸壁修复同期行吻合血管淋巴结组织移植及淋巴管静脉吻合治疗乳腺癌术后腋窝凹陷畸形及上肢淋巴水肿. 中华整形外科杂志, 2017, 33(增刊): 54-60.
29. 穆籣. 乳房再造同期上肢淋巴水肿治疗和预防的现状及趋势. 中华整形外科杂志, 2018, 34(4): 247-251.
30. Saaristo AM, Niemi TS, Viitanen TP, et al. Microvascular breast reconstruction and lymph node transfer for postmastectomy lymphedema patients. Ann Surg, 2012, 255(3): 468-473.
31. Nguyen AT, Chang EI, Suami H, et al. An algorithmic approach to simultaneous vascularized lymph node transfer with microvascular breast reconstruction. Ann Surg Oncol, 2015, 22(9): 2919-2924.
32. Ciudad P, Date S, Manrique OJ, et al. Recurrent advanced lower extremity lymphedema following initial successful vascularized lymph node transfer: A clinical and histopathological analysis. Arch Plast Surg, 2017,44(1): 87-89.
33. Scaglioni MF, Suami H. Lymphatic anatomy of the inguinal region in aid of vascularized lymph node flap harvesting. J Plast Reconstr Aesthet Surg, 2015, 68(3): 419-427.
34. Tourani SS, Taylor GI, Ashton MW. Anatomy of the superficial lymphatics of the abdominal wall and the upper thigh and its implications in lymphatic microsurgery. J Plast Reconstr Aesthet Surg, 2013, 66(10): 1390-1395.
35. Vignes S, Blanchard M, Yannoutsos A, et al. Complications of autologous lymph-node transplantation for limb lymphoedema. Eur J Vasc Endovasc Surg, 2013, 45(5): 516-520.
36. Sulo E, Hartiala P, Viitanen T, et al. Risk of donor-site lymphatic vessel dysfunction after microvascular lymph node transfer. J Plast Reconstr Aesthet Surg, 2015, 68(4): 551-558.
37. Dayan JH, Dayan E, Smith ML. Reverse lymphatic mapping: a new technique for maximizing safety in vascularized lymph node transfer. Plast Reconstr Surg, 2015, 135(1): 277-285.
38. Finegold DN, Baty CJ, Knickelbein KZ, et al. Connexin 47 mutations increase risk for secondary lymphedema following breast cancer treatment. Clin Cancer Res, 2012, 18(8): 2382-2390.
39. Poccia I, Lin CY, Cheng MH. Platysma-sparing vascularized submental lymph node flap transfer for extremity lymphedema. J Surg Oncol, 2017, 115(1): 48-53.
40. Chang DW. Lymphaticovenular bypass for lymphedema management in breast cancer patients: a prospective study. Plast Reconstr Surg, 2010,126(3): 752-758.
41. O’Brien BM, Hickey MJ, Hurley JV, et al. Microsurgical transfer of the greater omentum in the treatment of canine obstructive lymphoedema. Br J Plast Surg, 1990, 43(4): 440-446.
42. Nguyen AT, Suami H, Hanasono MM, et al. Long-term outcomes of the minimally invasive free vascularized omental lymphatic flap for the treatment of lymphedema. J Surg Oncol, 2017, 115(1): 84-89.

Chinese Journal of Reparative and Reconstructive Surgery

Research progress of vascularized lymph node transfer for extremity lymphedema

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