Review of treatment strategies after lymphadenectomy: from molecular therapeutics to immediate microsurgical lymphatic reconstruction

Cynthia Sung; Jin Wang; Jeff Chang; Alex K Wong

doi:10.1016/j.jvsv.2024.101844

Review of treatment strategies after lymphadenectomy: from molecular therapeutics to immediate microsurgical lymphatic reconstruction

J Vasc Surg Venous Lymphat Disord. 2024 Feb 3:101844. doi: 10.1016/j.jvsv.2024.101844. Online ahead of print.

Authors

Cynthia Sung¹, Jin Wang², Jeff Chang², Alex K Wong³

Affiliations

¹ Division of Plastic Surgery, City of Hope National Medical Center, Duarte, CA; Keck School of Medicine of USC, Los Angeles, CA.
² Division of Plastic Surgery, City of Hope National Medical Center, Duarte, CA.
³ Division of Plastic Surgery, City of Hope National Medical Center, Duarte, CA. Electronic address: alexwong@coh.org.

PMID: 38316291
DOI: 10.1016/j.jvsv.2024.101844

Abstract

Objective: Lymphedema is a common complication of cancer treatment, such as lymphadenectomy and radiation therapy. It is a debilitating condition with pathologic tissue changes that hinder effective curative treatment and jeopardize patients' quality of life. Various attempts to prevent the development of lymphedema have been made, with improvements in the incidence of the pathology. However, it is still prevalent among survivors of cancer. In this paper, we review both molecular therapeutics and immediate surgical lymphatic reconstruction as treatment strategies after lymphadenectomy. Specifically, we discuss pro-lymphangiogenic molecules that have proved efficient in animal models of lymphedema and clinical trials, and review currently available microsurgical techniques of immediate lymphatic reconstruction.

Methods: A literature search was conducted in PubMed, Embase, Cochrane Library, and Google Scholar through May 2022. Searches were done separately for molecular therapeutics and microsurgical techniques for immediate lymphatic reconstruction. Search terms used for (1) non-surgical methods include 'lymphangiogenesis,' 'lymphedema,' 'growth factor,' and 'gene therapy.' Search terms used for (2) surgical methods include 'lymphedema,' 'lymph node excision,' 'lymphatic vessels,' 'primary prevention,' and 'microsurgery.'

Results: Various pro-lymphangiogenic factors with therapeutic potential include VEGF-C, VEGF-D, HGF, bFGF, PDGF, IGF, Retinoic acid, Ang-1, S1P, TLR4, and IL-8. Microsurgical lymphatic reconstruction for prevention of secondary lymphedema includes lymphovenous anastomosis, vascularized lymph node flap transfer, and lymph-interpositional flap transfer, with promising clinical outcomes.

Conclusions: With growing knowledge of the lymphangiogenic pathway and lymphedema pathology and advances in microsurgical techniques to restore lymphatic channels, molecular and surgical approaches may represent a promising method for primary prevention of lymphedema.

Keywords: Immediate lymphatic reconstruction; Lymphangiogenesis; Lymphedema; Lymphovenous anastomosis.

Publication types

Review