New and Emerging Treatments for Lymphedema

Schaverien, Mark V.; Aldrich, Melissa B.

doi:10.1055/s-0038-1632403

Cited by 12 publications

(6 citation statements)

References 64 publications

(76 reference statements)

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“…While these procedures reduce swelling by an average of 25–46%, decrease symptom burden, lessen risk of progression to chronic LE, improve function and cosmesis, and decrease amount of time spent daily on therapy, they do not usually eliminate the need for daily maintenance therapy, such as bandaging [ 102 , 103 , 104 , 105 , 106 ]. Remarkably, though, LVB and VLNT patients experience significantly decreased cellulitis incidence following surgery [ 105 , 106 , 107 , 108 , 109 , 110 , 111 ]. Because of the variable reductions in limb swelling and the continued need for daily maintenance therapy, use of the microsurgeries in LE patients remains controversial.…”

Section: Diagnostic Imaging Of Dysfunctional Lymphatics For Staginmentioning

confidence: 99%

“…Because of the variable reductions in limb swelling and the continued need for daily maintenance therapy, use of the microsurgeries in LE patients remains controversial. In general, like conventional treatments, lymphovascular surgery is most effective when performed in earlier stages of LE, while there is still capacity for recovery of the lymphatic system [ 106 ]. Studies using ICG lymphography suggest that subjects with minimal dermal backflow are excellent candidates for lymphovascular surgeries.…”

Section: Diagnostic Imaging Of Dysfunctional Lymphatics For Staginmentioning

confidence: 99%

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The Development and Treatment of Lymphatic Dysfunction in Cancer Patients and Survivors

Aldrich

Rasmussen

Fife

et al. 2020

Cancers

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Breast-cancer-acquired lymphedema is routinely diagnosed from the appearance of irreversible swelling that occurs as a result of lymphatic dysfunction. Yet in head and neck cancer survivors, lymphatic dysfunction may not always result in clinically overt swelling, but instead contribute to debilitating functional outcomes. In this review, we describe how cancer metastasis, lymph node dissection, and radiation therapy alter lymphatic function, as visualized by near-infrared fluorescence lymphatic imaging. Using custom gallium arsenide (GaAs)-intensified systems capable of detecting trace amounts of indocyanine green administered repeatedly as lymphatic contrast for longitudinal clinical imaging, we show that lymphatic dysfunction occurs with cancer progression and treatment and is an early, sub-clinical indicator of cancer-acquired lymphedema. We show that early treatment of lymphedema can restore lymphatic function in breast cancer and head and neck cancer patients and survivors. The compilation of these studies provides insights to the critical role that the lymphatics and the immune system play in the etiology of lymphedema and associated co-morbidities.

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Section: Diagnostic Imaging Of Dysfunctional Lymphatics For Staginmentioning

confidence: 99%

Section: Diagnostic Imaging Of Dysfunctional Lymphatics For Staginmentioning

confidence: 99%

The Development and Treatment of Lymphatic Dysfunction in Cancer Patients and Survivors

Aldrich

Rasmussen

Fife

et al. 2020

Cancers

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“…A more stable and powerful method than using a single fixed time point for quantifying the long-term survival benefit was previously published in this journal. 2 This approach involves comparing the tail areas of survival curves-the larger, the better. For instance, one may calculate the areas between 12 months and 36 months of follow-up in Figure 2A.…”

Section: Quantifying the Long-term Survival Benefit Of Pembrolizumab ...mentioning

confidence: 99%

Financial Burden of Lymphedema Hospitalizations in the United States

et al. 2021

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Lymphedema, characterized by disruptions to the flow of lymphatic fluid, commonly occurs in cancer survivors and has been linked to increased depression, anxiety, pain, and low healthrelated quality of life. 1 Although there is no curative treatment, patients with lymphedema may receive outpatient care to help mitigate symptoms and reduce disease progression. 2 Without proper management, lymphedema can progress to recurrent cellulitis and hospitalization. The objective of this cohort study was to identify factors associated with high costs during lymphedema-related hospitalizations.Methods | We used the Healthcare Cost and Utilization Project National Inpatient Sample to identify lymphedema-related hospitalizations. 3 All hospitalizations for lymphedema and lymphedema-associated cellulitis were included by identifying adult patients (≥18 years old) who were admitted between January 1, 2012, and December 31, 2017, with (1) a primary diagnosis of lymphedema or (2) a primary diagnosis of cellulitis with a secondary diagnosis of lymphedema. Hospitalizations were classified by disease site (upper vs lower extremity). Among patients admitted for cellulitis, codes specified the disease site; in patients admitted for lymphedema, codes specified the disease site as postmastectomy (upper extremity) or other (lower extremity). International Classification of Diseases, and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes were used for site specification. Cost to charge ratios were used to estimate reimbursed hospitalization costs. This study was considered exempt by the University of North Carolina institutional review board because the database conforms to the definition of a limited data set and no informed consent is necessary for publicly available data sets. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.The statistical analysis was performed between January 4 and June 30, 2020. Multivariable logistic regression analysis was used to estimate the association between patient, disease, and hospital characteristics and extreme costs. Extreme costs were defined as those in the top 20th percentile of costs. Multivariable generalized gamma regression analy-

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“…Acquired lymphedema is a complex disease caused by cancer treatment or parasitic infection and few effective treatments are available for lymphedema. 1 , 2 , 3 It is urgently needed to develop new experimental approaches and therapeutic strategies. 3 In this study, we address a new role and mechanism of MSC‐ex (human umbilical cord Wharton's jelly mesenchymal stem cells derived exosome) in lymphedema treatment.…”

Section: Figurementioning

confidence: 99%

“… 1 , 2 , 3 It is urgently needed to develop new experimental approaches and therapeutic strategies. 3 In this study, we address a new role and mechanism of MSC‐ex (human umbilical cord Wharton's jelly mesenchymal stem cells derived exosome) in lymphedema treatment. We found that MSC‐ex delivered Ang‐2 (angiopoietin‐2) promoted lymphangiogenesis by upregulating Prox1 (Prospero Homeobox 1) mediated Akt signaling.…”

Section: Figurementioning

confidence: 99%

Exosomes derived from human umbilical cord Wharton's jelly mesenchymal stem cells ameliorate experimental lymphedema

Zhao

Zhang

Tan

et al. 2021

Clinical & Translational Med

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Dear Editor, Acquired lymphedema is a complex disease caused by cancer treatment or parasitic infection and few effective treatments are available for lymphedema. [1][2][3] It is urgently needed to develop new experimental approaches and therapeutic strategies. 3 In this study, we address a new role and mechanism of MSC-ex (human umbilical cord Wharton's jelly mesenchymal stem cells derived exosome) in lymphedema treatment. We found that MSC-ex delivered Ang-2 (angiopoietin-2) promoted lymphangiogenesis by upregulating Prox1 (Prospero Homeobox 1) mediated Akt signaling. MSC-ex can improve lymphatic function and ameliorate edema in a mouse model of acquired lymphedema.MSC-ex were isolated from the conditional medium of WJ-MSC, which were negative for CD206 and positive for CD29, CD44 (Figure 1A,D). Exosomal markers CD9, CD63, CD81, and TSG101 were expressed in MSC-ex, whereas Calnexin was not detected (Figure 1B,C). MSC-ex showed a spheroid shape, and the size was about 130 nm (Figure 1E-G). To investigate the effect of MSC-ex on edema, we developed an acquired lymphedema model via surgical dissection of lymphatic vessels in the mouse tail (Figure 1H). As shown in Figure 1I, subcutaneously administered Dir labeled MSC-ex localized in the injured tail at 24 h after treatment. MSC-ex treatment promoted lymphatic drainage in lymphedema mice as injected methylene blue across the site of incision at week 6, which was not found in PBS treated mice (Figure 1J). The edema determined by tail diameter was persisted in mice treated by PBS. However, the edema was markedly reduced at week 2 in mice treated by MSC-ex (Figure 1K). As lymphangiogenesis is crucial in lymphedema development after lymphatic ablation, 4,5 we analyzed the lymphatic anatomy and lymphangiogenesis in MSC-ex treated animals. Relative to PBS-treated animals, a relatively thinner dermis and epidermis was found in MSC-ex treated mice (Figure 1L). Number of LYVE-1 + (lymphatic endothelial hyluronan receptor-1) lymphaticsThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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New and Emerging Treatments for Lymphedema

Cited by 12 publications

References 64 publications

The Development and Treatment of Lymphatic Dysfunction in Cancer Patients and Survivors

The Development and Treatment of Lymphatic Dysfunction in Cancer Patients and Survivors

Financial Burden of Lymphedema Hospitalizations in the United States

Exosomes derived from human umbilical cord Wharton's jelly mesenchymal stem cells ameliorate experimental lymphedema

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