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Cited by 93Lymphatic System and DiseasesLymphatic Disorders and TreatmentsParasitic Diseases Research and Treatment

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The Vicious Circle of Stasis, Inflammation, and Fibrosis in Lymphedema

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Brown, Stav, Dayan, Joseph H., Kataru, Raghu P., Mehrara, Babak J.·2023·Plastic & Reconstructive Surgery
DOI 10.1097/prs.0000000000009866PMC PMC9881755
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Abstract

SUMMARY: Lymphedema is a progressive disease of the lymphatic system arising from impaired lymphatic drainage, accumulation of interstitial fluid, and fibroadipose deposition. Secondary lymphedema resulting from cancer treatment is the most common form of the disease in developed countries, affecting 15% to 40% of patients with breast cancer after lymph node dissection. Despite recent advances in microsurgery, outcomes remain variable and, in some cases, inadequate. Thus, development of novel treatment strategies is an important goal. Research over the past decade suggests that lymphatic injury initiates a chronic inflammatory response that regulates the pathophysiology of lymphedema. T-cell inflammation plays a key role in this response. In this review, the authors highlight the cellular and molecular mechanisms of lymphedema and discuss promising preclinical therapies.

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  • The chronic and progressive nature of lymphedema supports a conceptual feedforward model of disease progression in which lymphostasis, loss of shear signaling, inflammation, matrix deposition, and leaflet stiffening may drive valve dysfunction.

    “The chronic and progressive nature of lymphedema supports a conceptual feedforward model of disease progression (146) in which lymphostasis, loss of shear signaling, inflammation, matrix deposition, and leaflet stiffening may also drive valve dysfunction in lymphedema ( Figure 2c ).”

    From Transport and Immune Functions of the Lymphatic System. (2025) · cites this paper as [146]

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Metadata

Authors
Brown, S., Dayan, J. H., Kataru, R. P., & Mehrara, B. J.
Affiliations
Memorial Sloan Kettering Cancer Center (US)
ORCID
Venue
Plastic & Reconstructive Surgery
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2022-11-15
Volume
151
Issue
2
Pages
330e-341e
ISSN
0032-1052 (ISSN-L)
DOI
10.1097/prs.0000000000009866
PMC
PMC9881755
OpenAlex
W4318027450
Cited by
93
References
8
Citations by year
2026: 35 · 2025: 25 · 2024: 24 · 2023: 9
FWCI
1.77
Type
journal article
Language
en
Open access
Locations
  • Plastic & Reconstructive Surgery (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Heart, Lung, and Blood Institute (R01HL111130)
  • National Cancer Institute (P30CA008748, R01CA278599)
Topics
  • Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
  • Health Sciences › Medicine › Surgery › Lymphatic Disorders and Treatments
  • Health Sciences › Medicine › Infectious Diseases › Parasitic Diseases Research and Treatment
Keywords
lymphedema, secondary lymphedema, cancer-related lymphedema, breast cancer, lymph node dissection, chronic inflammation, T cell-mediated inflammation, fibrosis, Stasi, lymphatic injury, interstitial fluid accumulation, lymphatic microsurgery
MeSH terms
Fibrosis, Humans, Inflammation, Lymphatic System, Lymphedema, Lymphatic Vessels

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