Background and Objectives: Previously, we have shown that 9-cis retinoic acid (9-cis RA) stimulates lymphangiogenesis and limits postsurgical lymphedema in animal models when administered intraperitoneally. In this study, we investigate whether 9-cis RA contained within a single-use depot drug delivery system (DDS) can mitigate development of lymphedema in a clinically relevant mouse limb model. Methods:Hind limb lymphedema was induced via surgical lymphadenectomy and irradiation. Animals were divided into 2 treatment groups: 1) 9-cis RA DDS, 2) placebo DDS. Outcomes measured included paw thickness, lymphatic clearance and density, epidermal thickness, and collagen deposition.Results: Compared to control animals, 9-cis RA-treated animals had significantly less paw swelling from postoperative week 3 (P=0.04) until the final timepoint at week 6 (P=0.0007). Moreover, 9-cis RA-treated animals had significantly faster lymphatic clearance (P<0.05), increased lymphatic density (P=0.04), reduced lymphatic vessel size (P=0.02), reduced epidermal hyperplasia (P=0.04), and reduced collagen staining (P=0.10).Conclusions: Animals receiving 9-cis RA sustained-release implants at the time of surgery had improved lymphatic function and structure, indicating reduced lymphedema progression. Thus, we demonstrate that 9-cis RA contained within a single-use depot DDS has favorable properties in
Head and neck lymphedema (HNL) is a disfiguring disease affecting over 90% of patients treated for head and neck cancer. Animal models of lymphedema are used to test pharmacologic and microsurgical therapies; however, no animal model for HNL is described in the literature to date. In this study we describe the first reproducible rat model for HNL. Animals were subjected to two surgical protocols: (1) lymphadenectomy plus irradiation; and (2) sham surgery and no irradiation. Head and neck expansion was measured on post-operative days 15, 30 and 60. Magnetic resonance imaging (MRI) was acquired at the same time points. Lymphatic drainage was measured at day 60 via indocyanine green (ICG) lymphography, after which animals were sacrificed for histological analysis. Postsurgical lymphedema was observed 100% of the time. Compared to sham-operated animals, lymphadenectomy animals experienced significantly more head and neck swelling at all timepoints (P < 0.01). Lymphadenectomy animals had significantly slower lymphatic drainage for 6 days post-ICG injection (P < 0.05). Histological analysis of lymphadenectomy animals revealed 83% greater subcutis thickness (P = 0.008), 22% greater collagen deposition (P = 0.001), 110% greater TGFβ1+ cell density (P = 0.04), 1.7-fold increase in TGFβ1 mRNA expression (P = 0.03), and 114% greater T-cell infiltration (P = 0.005) compared to sham-operated animals. In conclusion, animals subjected to complete lymph node dissection and irradiation developed changes consistent with human clinical postsurgical HNL. This was evidenced by significant increase in all head and neck measurements, slower lymphatic drainage, subcutaneous tissue expansion, increased fibrosis, and increased inflammation compared to sham-operated animals.
Objective Incidental parathyroidectomy is a relatively common occurrence in thyroid surgery, which may lead to hypoparathyroidism and postoperative hypocalcemia, but it is not well studied in children. The objectives of this study were to determine the rate of incidental parathyroidectomy, identify potential risk factors, and investigate postoperative complications in children undergoing thyroidectomy. Study Design Retrospective cohort study. Setting Patients who underwent thyroidectomy over a 10-year period at a tertiary children’s hospital. Methods Pathology reports were reviewed to determine incidental parathyroid gland tissue. Additional data collected included patient demographics, type of procedure, underlying thyroid pathology, as well as immediate and long-term postoperative clinical outcomes. Results Of 209 patients, 65 (31%) had incidental parathyroidectomy. Several variables were associated with incidental parathyroidectomy on univariable analysis. However, in the final multivariable model, only thyroidectomy with lymph node dissection was associated with increased odds of having incidental parathyroidectomy (odds ratio, 3.3; P = .04; 95% CI, 1.1-9.8). After a median follow up of 1 year, a significantly higher percentage of patients with incidental parathyroidectomy had evidence of long-term hypoparathyroidism (9/62 [15%] vs 3/144 [2%], P = .001). Conclusion Incidental parathyroidectomy was relatively common in our pediatric thyroidectomy population, which may be a result of several anatomic, clinical, and surgeon-related factors. Close attention to parathyroid preservation with meticulous surgical technique is the most practical method of preventing long-term hypoparathyroidism and hypocalcemia.
Background The impact of thyroid nodule size is less useful in children who have smaller thyroid volumes than in adults. We investigate using a novel thyroid tumor ratio measurement in children with thyroid cancer. Methods Patient and pathologic characteristics were investigated via Student's t‐test in a univariate analysis for any correlation with the log‐transformed tumor ratio, followed by a multivariate linear regression. Results Of 75 patients with malignancy and tumor ratio information, mean ratio decreased with increasing age (p = 0.04). Out of several clinical factors, patients with lymph node metastases and those treated with postoperative radioactive iodine had significantly higher mean tumor ratios on multivariate analysis (p = 0.04 for both factors). Conclusions Our study is the first to describe thyroid tumor volume in pediatric thyroid cancer and shows that increased tumor ratio was associated with indicators of more advanced disease such as lymph node metastases and use of radioactive iodine.
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