Lymphatic Dysfunction and Associated Systemic Inflammation In Lymphedema, Assessed By Nirf-Li Imaging and Plasma Cytokine/Chemokine Analysis

<p>Breast cancer-related lymphedema (BCRL) manifests as swelling of the upper extremities and trunk as a result of lymphatic fluid buildup due to radiation therapy (RT), surgical lymph node removal, or chemotherapy. As there is currently no cure, BCRL treatment aims to improve quality of life (QOL). First-line treatment involves specialized massage therapy and the use of compression garments. Second-line treatments include reparative lymphatic microsurgeries such as lymphovenous bypass (LVB) and/or vascularized lymph node transplant (VLNT). There is a need for better understanding of the etiology of BCRL and lymphatic microsurgery outcomes. Blood specimens and near-infrared fluorescent lymphatic imaging (NIRF- LI)data from two different clinical studies were used. In the first study, a total of 67 breast cancer patients were longitudinally assessed for the development of BCRL (≥5% arm swelling) after RT. A total of 314 blood specimens were collected at four different time points (preoperatively, postoperatively, and at 6- and 12-months post-RT). Fourteen plasma cytokine/chemokine levels were assessed at each time point using a MILLIPLEXMAP human cytokine/chemokine magnetic bead panel. Plasma cytokine/chemokine levels in patients with ≥5% perometric arm swelling at 12 months post-RT were compared to those with ≤5% perometric arm swelling. GraphPad/Prism 9 non-parametric Mann-Whitney test analysis was used to determine the significance of each cytokine/chemokine. In the second study, lymphatic anatomy/function metric scores and plasma cytokine/chemokine levels in 15 established BCRL patients before and at pre-, six-, and 12 months after LVB/VLNT were measured and analyzed using Image J, Excel and GraphPad/Prism 9 paired Wilcoxon analysis. In the first study, plasma cytokines/chemokines G-CSF, GM-CSF, IFN-2α, IL-10, IL-12p40, IL-15, IL-17A, IL-1β, IL-2, IL-3, IL-6, and MIP-1β were significantly elevated at pre-ALND in those with ≥5% arm swelling at 12 months post-RT compared to those who did not. Subjects only displaying dermal backflow at 12 months post-RT had elevated MIP-1β and IL-6 plasma levels at baseline. In the second study, no plasma cytokine/chemokine levels were found to be significantly different between pre- and post LVB/VLNT. Metric scores at pre-, six- and 12 months post-LVB/VLNT also displayed no significant differences. These findings suggest that plasma cytokine/chemokines could be used as biomarkers for early LE detection and determination of those at highest risk of BCRL development. Lymphatic anatomy/function metric scores and plasma cytokines/chemokines did not differ significantly pre- and post-LVB/VLNT, suggesting that these reparative microsurgeries may resolve BCRL slowly, or only in a small subset of subjects. In conclusion, these studies show that 1) BCRL is a systemic, persistently inflammatory, disease, 2) NIRF-LI is a better tool for BCRL surveillance than perometric arm volume measurement and 3) reparative microsurgeries for BCRL need further study.</p>

Name thesis:degree_name

Masters of Science (MS)

Level thesis:degree_level

Thesis (MS)

Year dc:date.available

2023

Authors dc:creator

• Vang, Anna
• <p>0000-0001-5656-5906</p>

Contributors dc:contributor

• Melissa B. Aldrich
• John C. Rasmussen
• Michael J. Galko

• Lymphedema
• Breast cancer
• Cytokine/chemokine
• Systemic disease
• Microsurgeries
• Metric score
• Predictive biomarkers
• Medical Immunology
• Medicine and Health Sciences
• Quality Improvement

Repository record dc:identifier

https://digitalcommons.library.tmc.edu/utgsbs_dissertations/1274

OAI identifier oai:identifier

oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-2331