Improved Lymphangiogenesis Around Vascularized Lymph Node Flaps by Periodic Injection of Hyaluronidase in a Rodent Model

Overview

Journal Sci Rep

Specialty Science

Date 2024 Oct 18

PMID 39424818

Authors

Hwayeong Cheon

Linhai Chen

Sang Ah Kim

Ma Nessa Gelvosa

Joon Pio Hong

Jae Yong Jeon

Hyunsuk Peter Suh

Affiliations

Soon will be listed here.

Abstract

Vascularized lymph node transfer (VLNT) is an advanced surgical approach for secondary lymphedema (SLE) treatment, but tissue fibrosis around the lymph node flap (VLNF) inhibiting lymphangiogenesis is the biggest challenge undermining its therapeutic efficacy. This study explored the effects of periodic hyaluronidase (HLD) injection in reducing fibrosis and promoting lymphangiogenesis in 52 Sprague-Dawley rats with a VLNF over 13 weeks. The results demonstrated that HLD administration significantly enhanced swelling reduction, lymphatic drainage efficiency, and lymphatic vessel regeneration, with up to a 26% decrease in tissue fibrosis around the VLNF. These findings suggest that combining VLNT with periodic injections of HLD could substantially improve SLE treatment outcomes in clinical settings. It offers a promising direction for future therapeutic strategies and drug development aimed at increasing the efficacy of surgical treatment for SLE patients.

References

Chang D, Suami H, Skoracki R . A prospective analysis of 100 consecutive lymphovenous bypass cases for treatment of extremity lymphedema. Plast Reconstr Surg. 2013; 132(5):1305-1314. DOI: 10.1097/PRS.0b013e3182a4d626. View

Kung T, Champaneria M, Maki J, Neligan P . Current Concepts in the Surgical Management of Lymphedema. Plast Reconstr Surg. 2017; 139(4):1003e-1013e. DOI: 10.1097/PRS.0000000000003218. View

Visuri M, Honkonen K, Hartiala P, Tervala T, Halonen P, Junkkari H . VEGF-C and VEGF-C156S in the pro-lymphangiogenic growth factor therapy of lymphedema: a large animal study. Angiogenesis. 2015; 18(3):313-26. DOI: 10.1007/s10456-015-9469-2. View

Albeiroti S, Soroosh A, de la Motte C . Hyaluronan's Role in Fibrosis: A Pathogenic Factor or a Passive Player?. Biomed Res Int. 2015; 2015:790203. PMC: 4637089. DOI: 10.1155/2015/790203. View

Decio A, Taraboletti G, Patton V, Alzani R, Perego P, Fruscio R . Vascular endothelial growth factor c promotes ovarian carcinoma progression through paracrine and autocrine mechanisms. Am J Pathol. 2014; 184(4):1050-1061. DOI: 10.1016/j.ajpath.2013.12.030. View

Pappalardo M, Patel K, Cheng M . Vascularized lymph node transfer for treatment of extremity lymphedema: An overview of current controversies regarding donor sites, recipient sites and outcomes. J Surg Oncol. 2018; 117(7):1420-1431. DOI: 10.1002/jso.25034. View

Honkonen K, Visuri M, Tervala T, Halonen P, Koivisto M, Lahteenvuo M . Lymph node transfer and perinodal lymphatic growth factor treatment for lymphedema. Ann Surg. 2012; 257(5):961-7. DOI: 10.1097/SLA.0b013e31826ed043. View

Do J, Choi K, Ahn J, Jeon J . Effects of a complex rehabilitation program on edema status, physical function, and quality of life in lower-limb lymphedema after gynecological cancer surgery. Gynecol Oncol. 2017; 147(2):450-455. DOI: 10.1016/j.ygyno.2017.09.003. View

Roskoski Jr R . Vascular endothelial growth factor (VEGF) signaling in tumor progression. Crit Rev Oncol Hematol. 2007; 62(3):179-213. DOI: 10.1016/j.critrevonc.2007.01.006. View

10.

Moore H . Breast cancer survivorship. Semin Oncol. 2020; 47(4):222-228. DOI: 10.1053/j.seminoncol.2020.05.004. View

11.

Gallagher K, Marulanda K, Gray S . Surgical Intervention for Lymphedema. Surg Oncol Clin N Am. 2017; 27(1):195-215. DOI: 10.1016/j.soc.2017.08.001. View

12.

Allen Jr R, Cheng M . Lymphedema surgery: Patient selection and an overview of surgical techniques. J Surg Oncol. 2016; 113(8):923-31. DOI: 10.1002/jso.24170. View

13.

Maeda T, Yamamoto Y, Iwasaki D, Hayashi T, Funayama E, Oyama A . Lymphatic Reconnection and Restoration of Lymphatic Flow by Nonvascularized Lymph Node Transplantation: Real-Time Fluorescence Imaging Using Indocyanine Green and Fluorescein Isothiocyanate-Dextran. Lymphat Res Biol. 2017; 16(2):165-173. DOI: 10.1089/lrb.2016.0070. View

14.

Asaad M, Hanson S . Tissue Engineering Strategies for Cancer-Related Lymphedema. Tissue Eng Part A. 2021; 27(7-8):489-499. DOI: 10.1089/ten.TEA.2020.0378. View

15.

Nekoroski T, Paladini R, Sauder D, Frost G, Keller G . A recombinant human hyaluronidase sustained release gel for the treatment of post-surgical edema. Int J Dermatol. 2013; 53(6):777-85. DOI: 10.1111/ijd.12304. View

16.

Ciudad P, Sabbagh M, Agko M, Huang T, Manrique O, L C . Surgical Management of Lower Extremity Lymphedema: A Comprehensive Review. Indian J Plast Surg. 2019; 52(1):81-92. PMC: 6664851. DOI: 10.1055/s-0039-1688537. View

17.

Alderfer L, Wei A, Hanjaya-Putra D . Lymphatic Tissue Engineering and Regeneration. J Biol Eng. 2018; 12:32. PMC: 6296077. DOI: 10.1186/s13036-018-0122-7. View

18.

Greene A, Grant F, Slavin S, Maclellan R . Obesity-induced lymphedema: clinical and lymphoscintigraphic features. Plast Reconstr Surg. 2015; 135(6):1715-1719. DOI: 10.1097/PRS.0000000000001271. View

19.

Cormier J, Askew R, Mungovan K, Xing Y, Ross M, Armer J . Lymphedema beyond breast cancer: a systematic review and meta-analysis of cancer-related secondary lymphedema. Cancer. 2010; 116(22):5138-49. DOI: 10.1002/cncr.25458. View

20.

Schaverien M, Badash I, Patel K, Selber J, Cheng M . Vascularized Lymph Node Transfer for Lymphedema. Semin Plast Surg. 2018; 32(1):28-35. PMC: 5891655. DOI: 10.1055/s-0038-1632401. View