Exploratory use of docetaxel loaded acid-prepared mesoporous spheres for the treatment of malignant melanoma.

INTRODUCTION: Five year survival for metastatic melanoma (MM) is very low at <10%. Therapeutic options have been limited secondary to systemic toxicity. As a result there has been a growing movement towards developing targeted drug delivery models. Prior research of this group has demonstrated the effectiveness of acid-prepared mesoporous spheres (APMS-TEG) in delivering chemotherapeutic agents at a lower effective dose than systemic administration. This study aims to assess the ability of the previously developed APMS-TEG particles to deliver therapeutic doses of docetaxel for the treatment of melanoma. METHODS: In vitro experiments were performed to assess docetaxel loading onto APMS-TEG particles and release kinetics. Toxicity experiments were performed using docetaxel and docetaxel loaded APMS-TEG. The effect on cell growth was assessed using the MelJuSo, UACC903, and WM1205 melanoma cell lines. RESULTS: Docetaxel demonstrated statistically significant dose dependent reduction in growth of melanoma cells. In all three cell lines, doses of 1 nM were sufficient to produce statistically significant reduction in cell growth. Scanning electron micrographs demonstrate increased uptake of APMS-TEG particles by melanoma cells in the first 24 hours, with the majority within the first 4 hours. Unloaded APMS particles had no effect on the melanoma cells, demonstrating that the particles themselves are not toxic. APMS-TEG particles had a peak release of drug within the first hour, with equilibration thereafter. The 5, 10, and 20 nM loaded particles all had statistically significant reduction in cell growth than the control groups. DISCUSSION: The high potency against melanoma cells makes docetaxel a suitable choice for loading into APMS-TEG particles. Docetaxel loaded APMS-TEG particles demonstrate significant activity against malignant melanoma and thus offer an innovative approach to the treatment of metastatic melanoma.

Clinical impact of biopsy method on the quality of surgical management in melanoma.

BACKGROUND AND OBJECTIVES: Though guidelines recommend excisional biopsy for diagnosing melanoma, partial biopsy techniques are commonly performed, risking underestimation of Breslow depth and altering surgical management. Biopsy choice patterns by specialty and subsequent impact on surgical management was examined. METHODS: Retrospective review of the University of Vermont Cancer Registry. All patients with a single, primary cutaneous melanoma from 1/02 to 6/12 analyzed. RESULTS: Among 853 lesions analyzed, 606 had Breslow depth <1 mm. Dermatologists perform 62.6% of biopsies, favoring shave biopsies; surgeons favor excisional biopsies (48%), and primary care doctors favor punch biopsies (44.8%), (P < 0.001). Final Breslow depth was upstaged in 107 (12.5%); however, only 23 of 488 partial biopsies (4.7%) displayed a discrepancy great enough to change surgical recommendations (P < 0.001). There was no statistically significant relationship with presence of ulceration, regression, high Clark level, or high mitotic index. CONCLUSIONS: Partial biopsy techniques are commonly performed in diagnosing melanoma; especially among dermatologists, who perform the majority of biopsies. Though partial biopsies were less accurate in determining Breslow thickness; they rarely alter recommendations for surgical management. Predictive features could not be determined to identify the few cases where a Breslow discrepancy was clinically relevant.

Acute upper extremity arterial thrombosis and stroke in an unresected pheochromocytoma.

Pheochromocytoma is a rare cause of hypertension in the general population. Only isolated reports show an association with acute obstructive arterial thrombosis. A 50-year-old chronically noncompliant woman with a known unresected pheochromocytoma presented to the emergency department with ataxia. Imaging confirmed a right-sided ischemic stroke. During her hospital stay, the patient developed signs consistent with acute right upper extremity ischemia resulting from occlusion in the distal right subclavian, axillary, and proximal brachial arteries. Emergent open thrombectomy was successfully performed. In patients with an unresected pheochromocytoma, one must consider acute arterial thrombosis as a rare but potentially limb-threatening and even life-threatening complication.