Development of a Nanocrystalline Paclitaxel Formulation for Hipec Treatment

To develop a nanocrystalline paclitaxel formulation with a high paclitaxel-to-stabilizer ratio which can be used for hyperthermic intraperitoneal chemotherapy (HIPEC). Paclitaxel (PTX) nanocrystals were prepared via wet milling using Pluronic F127(A (R)) as stabilizer. The suitability of paclitaxel nanosuspensions for HIPEC treatment was evaluated by analyzing the cytotoxicity of both stabilizer and formulation, and by determining the maximum tolerated dose (MTD) and bioavailability. The effect on tumor growth was evaluated by magnetic resonance imaging (MRI) at day 7 and 14 after HIPEC treatment in rats with peritoneal carcinomatosis of ovarian origin. Monodisperse nanosuspensions (+/- 400 nm) were developed using Pluronic F127(A (R)) as single additive. The cytotoxicity and MTD of this nanocrystalline formulation was similar compared to Taxol(A (R)), while its bioavailability was higher. MRI data after HIPEC treatment with a PTX nanocrystalline suspension showed a significant reduction of tumor volume compared to the non-treated group. Although no significant differences on tumor volume were observed between Taxol(A (R)) and the nanosuspension, the rats treated with the nanosuspension recovered faster following the HIPEC procedure. Nanosuspensions with a high paclitaxel-to-stabilizer ratio are of interest for the treatment of peritoneal carcinomatosis of ovarian origin via HIPEC

Treatment of buccal mucosal carcinomas: A survey amongst head and neck surgeons in the Netherlands

Abstract Objective Currently, there is no up‐to‐date guideline for the treatment of buccal mucosal squamous cell carcinoma (BMSCC) in the Netherlands. A questionnaire was used to investigate the opinions of Dutch head and neck surgeons on BMSCC of the cheek treatment. Methods A questionnaire was sent to all 91 head and neck surgeons in the Netherlands. Their opinions on surgical tumor‐free margins, through‐and‐through defects, and indications for local adjuvant therapy were questioned. Results The response rate was 51%. To prevent a through‐and‐through defect, 67% of the surgeons would accept a deep clinical (macroscopic) margin of ≤5 mm. The less adverse histological characteristics a tumor has, the less consensus there is amongst the surgeons for local adjuvant treatment in case of close margins. Conclusion There is no consensus amongst Dutch head and neck surgeons about the optimal treatment for BMSCC of the cheek. There are different opinions on acceptable resection margins, indications for a through‐and‐through defect, and indications for adjuvant treatment. BMSCC of the cheek treatment should be more uniform and less surgeon dependent. Level of evidence N/

A prospective longitudinal study on endocrine dysfunction following treatment of laryngeal or hypopharyngeal carcinoma

Objectives The incidences of hypo(para)thyroidism were assessed prospectively in 137 consecutive patients with laryngeal (84.7%) or hypopharyngeal (15.3%) carcinoma who were treated with surgery and/or radiotherapy between 2004 and 2006. Material and methods Laboratory studies were performed in patients before primary or salvage treatment of a laryngeal or hypopharyngeal carcinoma and were repeated 6, 12, 18 and 24 months after treatment. All patients were evaluated for the development of hypo(para)thyroidism, and the presence of autoantibodies. The association of hypothyroidism was analyzed against several patient parameters including tumor and treatment characteristics. Results The incidence of hypothyroidism following treatment of laryngeal and hypopharyngeal carcinoma was 47.4%: 27.7% subclinical hypothyroidism and 19.7% clinical hypothyroidism. The median time to develop hypothyroidism was 10 months. The incidence of hypoparathyroidism was 7.3%. Univariate analysis showed that patients with laryngectomy, hemithyroidectomy, neck dissection, paratracheal lymph node dissection and radiotherapy had a higher risk of developing hypothyroidism. Multivariate analysis showed laryngectomy, hemithyroidectomy, neck dissection and age to be predictive factors for the development of hypothyroidism. The combination of surgery and radiotherapy increased this risk. Hemithyroidectomy was the most important risk factor. Conclusion The incidence rate of hypothyroidism after treatment for laryngeal or hypopharyngeal cancer in this largest prospective study is high (47.4%), especially after combination treatment. Based on the intervals between treatment and the development of hypothyroidism, thyroid testing before treatment, every 3 months during the first year, every 6 months the second year and annually thereafter is recommended as screening procedure

Surgical management of gynecomastia - a 10-year analysis

BACKGROUND: Gynecomastia is defined as the benign enlargement of the male breast. Most studies on surgical treatment of gynecomastia show only small series and lack histopathology results. The aim of this study was to analyze the surgical approach in the treatment of gynecomastia and the related outcome over a 10-year period. PATIENTS AND METHODS: All patients undergoing surgical gynecomastia corrections in our department between 1996 and 2006 were included for retrospective evaluation. The data were analyzed for etiology, stage of gynecomastia, surgical technique, complications, risk factors, and histological results. RESULTS: A total of 100 patients with 160 operations were included. Techniques included subcutaneous mastectomy alone or with additional hand-assisted liposuction, isolated liposuction, and formal breast reduction. Atypical histological findings were found in 3% of the patients (spindle-cell hemangioendothelioma, papilloma). The surgical revision rate among all patients was 7%. Body mass index and a weight of the resected specimen higher than 40 g were identified as significant risk factors for complications (p < 0.05). CONCLUSIONS: The treatment of gynecomastia requires an individualized approach. Caution must be taken in performing large resections, which are associated with increased complication rates. Histological tissue analysis should be routinely performed in all true gynecomastia corrections, because histological results may reveal atypical cellular pathology