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Purpose The goal of this study was to investigate the association between blood draws, injections, blood pressure readings, trauma, cellulitis in the at-risk arm, and air travel and increases in arm volume in a cohort of patients treated for breast cancer and screened for lymphedema. Patients and Methods Between 2005 and 2014, patients undergoing treatment of breast cancer at our institution were screened prospectively for lymphedema. Bilateral arm volume measurements were performed preoperatively and postoperatively using a Perometer. At each measurement, patients reported the number of blood draws, injections, blood pressure measurements, trauma to the at-risk arm(s), and number of flights taken since their last measurement. Arm volume was quantified using the relative volume change and weight-adjusted change formulas. Linear random effects models were used to assess the association between relative arm volume (as a continuous variable) and nontreatment risk factors, as well as clinical characteristics. Results In 3,041 measurements, there was no significant association between relative volume change or weight-adjusted change increase and undergoing one or more blood draws (P = .62), injections (P = .77), number of flights (one or two [P = .77] and three or more [P = .91] v none), or duration of flights (1 to 12 hours [P = .43] and 12 hours or more [P = .54] v none). By multivariate analysis, factors significantly associated with increases in arm volume included body mass index ≥ 25 (P = .0236), axillary lymph node dissection (P < .001), regional lymph node irradiation (P = .0364), and cellulitis (P < .001). Conclusion This study suggests that although cellulitis increases risk of lymphedema, ipsilateral blood draws, injections, blood pressure readings, and air travel may not be associated with arm volume increases. The results may help to educate clinicians and patients on posttreatment risk, prevention, and management of lymphedema.
Taxane-based chemotherapy for the treatment of breast cancer is associated with fluid retention in the extremities; however, its association with development of breast cancer-related lymphedema is unclear. We sought to determine if adjuvant taxane-based chemotherapy increased risk of lymphedema or mild swelling of the upper extremity. 1121 patients with unilateral breast cancer were prospectively screened for lymphedema with perometer measurements. Lymphedema was defined as a relative volume change (RVC) of ≥10 % from preoperative baseline. Mild swelling was defined as RVC 5- <10 %. Clinicopathologic characteristics were obtained via medical record review. Kaplan–Meier and Cox proportional hazard analyses were performed to determine lymphedema rates and risk factors. 29 % (324/1121) of patients were treated with adjuvant taxane-based chemotherapy. The 2-year cumulative incidence of lymphedema in the overall cohort was 5.27 %. By multivariate analysis, axillary lymph node dissection (ALND) (p < 0.0001), higher body mass index (p = 0.0007), and older age at surgery (p = 0.04) were significantly associated with increased risk of lymphedema; however, taxane chemotherapy was not significant when compared to no chemotherapy and non-taxane chemotherapy (HR 1.14, p = 0.62; HR 1.56, p = 0.40, respectively). Chemotherapy with docetaxel was significantly associated with mild swelling on multivariate analysis in comparison to both no chemotherapy and non-taxane chemotherapy groups (HR 1.63, p = 0.0098; HR 2.15, p = 0.02, respectively). Patients who receive taxane-based chemotherapy are not at an increased risk of lymphedema compared to patients receiving no chemotherapy or non-taxane adjuvant chemotherapy. Those treated with docetaxel may experience mild swelling, but this does not translate into subsequent lymphedema.
During embryonic development, the paraxial mesoderm becomes segmented into somites, within which proliferative muscle progenitors and muscle fibers establish the skeletal musculature. Here, we demonstrate that a gene network previously implicated in somite boundary formation, involving the transcriptional regulators Tbx6, Mesp-b and Ripply1, also confers spatial and temporal regulation to skeletal myogenesis in zebrafish. We show that Tbx6 directly regulates mesp-b and ripply1 expression in vivo, and that the interactions within the regulatory network are largely conserved among vertebrates. Mesp-b is necessary and sufficient for the specification of a subpopulation of muscle progenitors, the central proportion of the Pax3 + /Pax7 + dermomyotome. Conditional ubiquitous expression indicates that Mesp-b acts by inhibiting myogenic differentiation and by inducing the dermomyotome marker meox1. By contrast, Ripply1 induces a negative-feedback loop by promoting Tbx6 protein degradation. Persistent Tbx6 expression in Ripply1 knockdown embryos correlates with a deficit in dermomyotome and myotome marker gene expression, suggesting that Ripply1 promotes myogenesis by terminating Tbx6-dependent inhibition of myogenic maturation. Together, our data suggest that Mesp-b is an intrinsic upstream regulator of skeletal muscle progenitors and that, in zebrafish, the genes regulating somite boundary formation also regulate the development of the dermomyotome in the anterior somite compartment.
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