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Is Lymphedema a Systemic Disease? A Paired Molecular and Histological Analysis of the Affected and Unaffected Tissue in Lymphedema Patients

Secondary lymphedema is a chronic, debilitating disease and one of the most common side effects of oncologic surgery, substantially decreasing quality of life. Despite the progress conducted in lymphedema research, the underlying pathomechanisms remain elusive. Lymphedema is considered to be a disea...

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Autores principales: Wolf, Stefan, von Atzigen, Julia, Kaiser, Bettina, Grünherz, Lisanne, Kim, Bong-Sung, Giovanoli, Pietro, Lindenblatt, Nicole, Gousopoulos, Epameinondas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9687735/
https://www.ncbi.nlm.nih.gov/pubmed/36421681
http://dx.doi.org/10.3390/biom12111667
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author Wolf, Stefan
von Atzigen, Julia
Kaiser, Bettina
Grünherz, Lisanne
Kim, Bong-Sung
Giovanoli, Pietro
Lindenblatt, Nicole
Gousopoulos, Epameinondas
author_facet Wolf, Stefan
von Atzigen, Julia
Kaiser, Bettina
Grünherz, Lisanne
Kim, Bong-Sung
Giovanoli, Pietro
Lindenblatt, Nicole
Gousopoulos, Epameinondas
author_sort Wolf, Stefan
collection PubMed
description Secondary lymphedema is a chronic, debilitating disease and one of the most common side effects of oncologic surgery, substantially decreasing quality of life. Despite the progress conducted in lymphedema research, the underlying pathomechanisms remain elusive. Lymphedema is considered to be a disease affecting an isolated extremity, yet imaging studies suggest systemic changes of the lymphatic system in the affected patients. To evaluate potential systemic manifestations in lymphedema, we collected matched fat and skin tissue from the edematous and non-edematous side of the same 10 lymphedema patients as well as anatomically matched probes from control patients to evaluate whether known lymphedema manifestations are present systemically and in comparison to health controls. The lymphedematous tissue displayed various known hallmarks of lymphedema compared to the healthy controls, such as increased epidermis thickness, collagen deposition in the periadipocyte space and the distinct infiltration of CD4+ cells. Furthermore, morphological changes in the lymphatic vasculature between the affected and unaffected limb in the same lymphedema patient were visible. Surprisingly, an increased collagen deposition as well as CD4 expression were also detectable in the non-lymphedematous tissue of lymphedema patients, suggesting that lymphedema may trigger systemic changes beyond the affected extremity.
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spelling pubmed-96877352022-11-25 Is Lymphedema a Systemic Disease? A Paired Molecular and Histological Analysis of the Affected and Unaffected Tissue in Lymphedema Patients Wolf, Stefan von Atzigen, Julia Kaiser, Bettina Grünherz, Lisanne Kim, Bong-Sung Giovanoli, Pietro Lindenblatt, Nicole Gousopoulos, Epameinondas Biomolecules Article Secondary lymphedema is a chronic, debilitating disease and one of the most common side effects of oncologic surgery, substantially decreasing quality of life. Despite the progress conducted in lymphedema research, the underlying pathomechanisms remain elusive. Lymphedema is considered to be a disease affecting an isolated extremity, yet imaging studies suggest systemic changes of the lymphatic system in the affected patients. To evaluate potential systemic manifestations in lymphedema, we collected matched fat and skin tissue from the edematous and non-edematous side of the same 10 lymphedema patients as well as anatomically matched probes from control patients to evaluate whether known lymphedema manifestations are present systemically and in comparison to health controls. The lymphedematous tissue displayed various known hallmarks of lymphedema compared to the healthy controls, such as increased epidermis thickness, collagen deposition in the periadipocyte space and the distinct infiltration of CD4+ cells. Furthermore, morphological changes in the lymphatic vasculature between the affected and unaffected limb in the same lymphedema patient were visible. Surprisingly, an increased collagen deposition as well as CD4 expression were also detectable in the non-lymphedematous tissue of lymphedema patients, suggesting that lymphedema may trigger systemic changes beyond the affected extremity. MDPI 2022-11-11 /pmc/articles/PMC9687735/ /pubmed/36421681 http://dx.doi.org/10.3390/biom12111667 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wolf, Stefan
von Atzigen, Julia
Kaiser, Bettina
Grünherz, Lisanne
Kim, Bong-Sung
Giovanoli, Pietro
Lindenblatt, Nicole
Gousopoulos, Epameinondas
Is Lymphedema a Systemic Disease? A Paired Molecular and Histological Analysis of the Affected and Unaffected Tissue in Lymphedema Patients
title Is Lymphedema a Systemic Disease? A Paired Molecular and Histological Analysis of the Affected and Unaffected Tissue in Lymphedema Patients
title_full Is Lymphedema a Systemic Disease? A Paired Molecular and Histological Analysis of the Affected and Unaffected Tissue in Lymphedema Patients
title_fullStr Is Lymphedema a Systemic Disease? A Paired Molecular and Histological Analysis of the Affected and Unaffected Tissue in Lymphedema Patients
title_full_unstemmed Is Lymphedema a Systemic Disease? A Paired Molecular and Histological Analysis of the Affected and Unaffected Tissue in Lymphedema Patients
title_short Is Lymphedema a Systemic Disease? A Paired Molecular and Histological Analysis of the Affected and Unaffected Tissue in Lymphedema Patients
title_sort is lymphedema a systemic disease? a paired molecular and histological analysis of the affected and unaffected tissue in lymphedema patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9687735/
https://www.ncbi.nlm.nih.gov/pubmed/36421681
http://dx.doi.org/10.3390/biom12111667
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