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Cellulitis Is Associated with Severe Breast Cancer-Related Lymphedema: An Observational Study of Tissue Composition.

ABSTRACT: Cellulitis is a common complication in Breast Cancer-Related Lymphedema (BCRL). The excess amount of fat and lean mass in BCRL is a vital factor in patient stratification, prognosis, and treatments. However, it is not known whether cellulitis is associated with the excess fat and lean mass in BCRL. Therefore, this prospective observational study was designed to fundamentally understand the heterogonous biocomposition of BCRL. For this study, we consecutively enrolled 206 patients with unilateral BCRL between January 2019 and February 2020. All patients underwent Dual-Energy X-Ray Absorptiometry scans, bioimpedance spectroscopy, indocyanine green lymphangiography comprehensive history of potential risk factors, and a clinical exam. Multivariate linear and beta regression models were used to determine the strength of association and margins effect. Sixty-nine patients (33%) had at least one previous episode of cellulitis. Notably, a previous episode of cellulitis was associated with 20 percentage points more excess fat and 10 percentage points more excess lean mass compared to patients without cellulitis (p < 0.05). Moreover, each 1 increase in the patients BMI was associated with a 0.03 unit increase in the fat mass proportion of the lymphedema arm. Cellulitis was associated with more excess fat and lean arm mass in BCRL. In addition, patients BMI affect the proportion of fat mass in the arm.

SUBMITTER: Jorgensen MG

PROVIDER: S-EPMC8303539 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Cellulitis Is Associated with Severe Breast Cancer-Related Lymphedema: An Observational Study of Tissue Composition.

Jørgensen Mads Gustaf MG Hermann Anne Pernille AP Madsen Anette Riis AR Christensen Steffanie S Ingwersen Kim Gordon KG Thomsen Jørn Bo JB Sørensen Jens Ahm JA

Cancers 20210717 14

Cellulitis is a common complication in Breast Cancer-Related Lymphedema (BCRL). The excess amount of fat and lean mass in BCRL is a vital factor in patient stratification, prognosis, and treatments. However, it is not known whether cellulitis is associated with the excess fat and lean mass in BCRL. Therefore, this prospective observational study was designed to fundamentally understand the heterogonous biocomposition of BCRL. For this study, we consecutively enrolled 206 patients with unilateral ...[more]

PMID: 34298799

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Project description:Secondary lymphedema (LE) following breast cancer-related surgery is a life-long complication, which currently has no cure. LE induces significant regional adipose tissue deposition, requiring liposuction as a treatment. Here, we aimed to elucidate the transcriptional, metabolomic, and lipidomic signature of the adipose tissue developed due to the surgery-induced LE in short- and long-term LE patients and compared the transcriptomic landscape of LE adipose tissue to the obesity-induced adipose tissue. Adipose tissue biopsies were obtained from breast cancer-operated females with LE from the affected and non-affected arms (n = 20 patients). To decipher the molecular properties of the LE adipose tissue, we performed RNA sequencing, metabolomics, and lipidomics combined with bioinformatics analyses. Differential gene expression data from a cohort of lean and obese patients without LE was used for comparisons. Integrative analysis of functional genomics revealed that inflammatory response, cell chemotaxis, and angiogenesis were upregulated biological processes in the LE arm, indicating a sustained inflammation in the edematous adipose tissue; whereas, epidermal differentiation, cell-cell junction organization, water homeostasis, and neurogenesis were downregulated in the LE arm. Surprisingly, only a few genes were found to be the same in the LE-induced and the obesity-induced adipose tissue expansion, indicating a different type of adipose tissue development in these two conditions. In metabolomics analysis, we found reduced levels of a branched-chain amino acid valine in the LE arm and downregulation of the mRNA levels of its transporter SLC6A15. Lipidomics analyses did not show any significant differences between the LE and non-LE arms, suggesting that other factors affect the lipid composition of the adipose tissue more than the LE in these patients. Our results provide a detailed molecular characterization of adipose tissue in secondary LE after breast cancer-related surgery. We also show distinct differences in transcriptomic signatures between LE-induced adipose tissue and obesity-induced adipose tissue, but only minor differences in metabolome and lipidome between the LE and the non-LE arm.

Project description:PurposeTo profile the prescription for and adherence to breast cancer-related lymphedema (BCRL) self-care modalities among breast cancer (BrCa) survivors with BCRL in a 12-month randomized weightlifting trial.MethodsWe developed a questionnaire that assessed prescription for and adherence to 10 BCRL self-care modalities that included physical therapy exercise, pneumatic compression pump, medication, lymphedema bandaging, arm elevation, self-administered lymphatic drainage, therapist-administered lymphatic drainage, compression garments, skin care, and taping. We measured prescription for and adherence to BCRL self-care modalities at baseline, 3, 6, and 12 months. Longitudinal logistic regression was used to estimate the odds ratio (OR) and 95 % confidence interval (95 % CI) associated with prescription for and adherence to BCRL modalities over time.ResultsThis study included 141 BrCa survivors with BCRL. Women were prescribed an average of 3.6 ± 2.1 BCRL self-care modalities during the study. The prescription for therapist-administered lymphatic drainage (OR = 0.92, 95 % CI 0.88-0.96), pneumatic compression pump use (OR = 0.94, 95 % CI 0.89-0.98), and bandaging (OR = 0.96, 95 % CI 0.93-0.99) decreased over 12 months of follow-up. No other prescribed BCRL self-care modalities changed during the study. Over 12 months, the average adherence to all BCRL self-care modalities varied with 13, 24, 32, and 31 % of women reporting <25, 25-49, 50-74, and ≥75 % adherence, respectively. Over 12 months, there was a noticeable change from high to low adherence in self-administered lymphatic drainage, such that there was a 15 % increased likelihood of adherence <25 % compared to ≥75 % (OR = 1.15 (95 % CI 1.05-1.26); p = 0.002). The adherence patterns of all other modalities did not change over follow-up.ConclusionsOur findings suggest the prescription for BCRL self-care modalities is variable. The average adherence to BCRL self-care was non-optimal. Future research is necessary to prepare BrCa survivors with the knowledge, skills, abilities, and resources necessary to care for this lifelong condition.

Project description:Lymphedema can be a debilitating condition, causing a great decrease in a person's quality of life (QoL). Treatment with lymphaticovenular anastomosis (LVA), in which an anastomosis is created between the lymphatic and venous system, may attenuate lymphedema symptoms and reduce swelling. In this study, we share the results using LVA to treat breast cancer-related lymphedema (BCRL) at our institution.Patients were eligible for inclusion if they suffered from unilateral BCRL, if functional lymphatics were available, if compression therapy was used for at least 6 months, and if the follow-up was 12 months at minimum. Lymph vessel functionality was assessed preoperatively using indocyanine green (ICG). During surgery, 1-3 anastomoses were created and shunt patency was confirmed using ICG. Arm volumes were measured before surgery and at 6- and 12-month follow-up. QoL was measured before surgery and at 6-month follow-up. Arm volume differences between the healthy arm and affected arm were compared between the time points.Twenty-nine consecutive female patients with unilateral BCRL were included. The preoperative mean difference in arm volumes was 701 ± 435 ml (36.9%). This was reduced to 496 ± 302 ml (24.7%) at 6-month follow-up (p = 0.00). At 12-month follow-up, the mean difference in arm volume was 467 ± 303 ml (23.5%) (p = 0.02). The overall perceived QoL was increased from 5.8 ± 1.1 to 7.4 ± 0.7 (p = 0.00). The functionality score decreased from 2.2 to 1.8 (p = 0.00), the appearance score decreased from 2.6 to 1.9 (p = 0.00), the symptoms score decreased from 2.8 to 1.8 (p = 0.00), and the mood score decreased from 2.7 to 1.5 (p = 0.00). Fifteen patients (53.6%) were able to discontinue the use of compression garment.Treatment with LVAs is effective in reducing arm volume difference in patients suffering from BCRL. Although no complete reduction of the edema was achieved at 12-month follow-up, the procedure significantly increased the patients' QoL.

Project description:BackgroundBreast cancer treatment-related lymphedema (BCRL) arises from a mechanical insufficiency following cancer therapies. Early BCRL detection and personalized intervention require an improved understanding of the physiological processes that initiate lymphatic impairment. Here, internal magnetic resonance imaging (MRI) measures of the tissue microenvironment were paired with clinical measures of tissue structure to test fundamental hypotheses regarding structural tissue and muscle changes after the commonly used therapeutic intervention of manual lymphatic drainage (MLD).Methods and resultsMeasurements to identify lymphatic dysfunction in healthy volunteers (n = 29) and patients with BCRL (n = 16) consisted of (1) limb volume, tissue dielectric constant, and bioelectrical impedance (i.e., non-MRI measures); (2) qualitative 3 Tesla diffusion-weighted, T1-weighted and T2-weighted MRI; and (3) quantitative multi-echo T2 MRI of the axilla. Measurements were repeated in patients immediately following MLD. Normative control and BCRL T2 values were quantified and a signed Wilcoxon Rank-Sum test was applied (significance: two-sided p < 0.05). Non-MRI measures yielded significant capacity for discriminating between arms with versus without clinical signs of BCRL, yet yielded no change in response to MLD. Alternatively, a significant increase in deep tissue T2 on the involved (pre T2 = 0.0371 ± 0.003 seconds; post T2 = 0.0389 ± 0.003; p = 0.029) and contralateral (pre T2 = 0.0365 ± 0.002; post T2 = 0.0395 ± 0.002; p < 0.01) arms was observed. Trends for larger T2 increases on the involved side after MLD in patients with stage 2 BCRL relative to earlier stages 0 and 1 BCRL were observed, consistent with tissue composition changes in later stages of BCRL manifesting as breakdown of fibrotic tissue after MLD in the involved arm. Contrast consistent with relocation of fluid to the contralateral quadrant was observed in all stages.ConclusionQuantitative deep tissue T2 MRI values yielded significant changes following MLD treatment, whereas non-MRI measurements did not vary. These findings highlight that internal imaging measures of tissue composition may be useful for evaluating how current and emerging therapies impact tissue function.

Dataset Information

Cellulitis Is Associated with Severe Breast Cancer-Related Lymphedema: An Observational Study of Tissue Composition.

Publications

Cellulitis Is Associated with Severe Breast Cancer-Related Lymphedema: An Observational Study of Tissue Composition.

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