Radiosensitization by BRAF inhibitor therapy—mechanism and frequency of toxicity in melanoma patients

This study shows radiosensitization by BRAF inhibitors in clinical practice and ex vivo by fluorescence in situ hybridization of chromosomal breaks. Nevertheless, radiotherapy with concomitant BRAF inhibitor therapy is feasible with an acceptable increase in toxicity. Vemurafenib is a more potent radiosensitizer than dabrafenib in both the patient study and the ex vivo experiment

A systematic review of natural health product treatment for vitiligo

<p>Abstract</p> <p>Background</p> <p>Vitiligo is a hypopigmentation disorder affecting 1 to 4% of the world population. Fifty percent of cases appear before the age of 20 years old, and the disfigurement results in psychiatric morbidity in 16 to 35% of those affected.</p> <p>Methods</p> <p>Our objective was to complete a comprehensive, systematic review of the published scientific literature to identify natural health products (NHP) such as vitamins, herbs and other supplements that may have efficacy in the treatment of vitiligo. We searched eight databases including MEDLINE and EMBASE for vitiligo, leucoderma, and various NHP terms. Prospective controlled clinical human trials were identified and assessed for quality.</p> <p>Results</p> <p>Fifteen clinical trials were identified, and organized into four categories based on the NHP used for treatment. 1) L-phenylalanine monotherapy was assessed in one trial, and as an adjuvant to phototherapy in three trials. All reported beneficial effects. 2) Three clinical trials utilized different traditional Chinese medicine products. Although each traditional Chinese medicine trial reported benefit in the active groups, the quality of the trials was poor. 3) Six trials investigated the use of plants in the treatment of vitiligo, four using plants as photosensitizing agents. The studies provide weak evidence that photosensitizing plants can be effective in conjunction with phototherapy, and moderate evidence that <it>Ginkgo biloba </it>monotherapy can be useful for vitiligo. 4) Two clinical trials investigated the use of vitamins in the therapy of vitiligo. One tested oral cobalamin with folic acid, and found no significant improvement over control. Another trial combined vitamin E with phototherapy and reported significantly better repigmentation over phototherapy only. It was not possible to pool the data from any studies for meta-analytic purposes due to the wide difference in outcome measures and poor quality ofreporting.</p> <p>Conclusion</p> <p>Reports investigating the efficacy of NHPs for vitiligo exist, but are of poor methodological quality and contain significant reporting flaws. L-phenylalanine used with phototherapy, and oral <it>Ginkgo biloba </it>as monotherapy show promise and warrant further investigation.</p

Original article title: "Comparison of therapeutic efficacy of topical corticosteroid and oral zinc sulfate-topical corticosteroid combination in the treatment of vitiligo patients: a clinical trial"

<p>Abstract</p> <p>Background</p> <p>Vitiligo is the most prevalent pigmentary disorder which occurs worldwide, with an incidence rate between 0.1-4 percent. It is anticipated that the discovery of biological pathways of vitiligo pathogenesis will provide novel therapeutic and prophylactic targets for future approaches to the treatment and prevention of vitiligo. The purposes of this study were evaluating the efficacy of supplemental zinc on the treatment of vitiligo.</p> <p>Methods</p> <p>This randomized clinical trial was conducted for a period of one year. Thirty five patients among 86 participants were eligible to entrance to the study. The patients in two equal randomized groups took topical corticosteroid and combination of oral zinc sulfate-topical corticosteroid.</p> <p>Results</p> <p>The mean of responses in the corticosteroid group and the zinc sulfate-corticosteroid combination group were 21.43% and 24.7%, respectively.</p> <p>Conclusion</p> <p>Although, the response to corticosteroid plus zinc sulfate was more than corticosteroid, there was no statistically significant difference between them. It appeared that more robust long-term randomized controlled trials on more patients, maybe with higher doses of zinc sulfate, are needed to fully establish the efficacy of oral zinc in management of vitiligo.</p> <p>Trial Registration</p> <p>chiCTRTRC10000930</p

Ginkgo biloba for the treatment of vitilgo vulgaris: an open label pilot clinical trial

<p>Abstract</p> <p>Background</p> <p>Vitiligo is a common hypopigmentation disorder with significant psychological impact if occurring before adulthood. A pilot clinical trial to determine the feasibility of an RCT was conducted and is reported here.</p> <p>Methods</p> <p>12 participants 12 to 35 years old were recruited to a prospective open-label pilot trial and treated with 60 mg of standardized <it>G. biloba </it>two times per day for 12 weeks. The criteria for feasibility included successful recruitment, 75% or greater retention, effectiveness and lack of serious adverse reactions. Effectiveness was assessed using the Vitiligo Area Scoring Index (VASI) and the Vitiligo European Task Force (VETF), which are validated outcome measures evaluating the area and intensity of depigmentation of vitiligo lesions. Other outcomes included photographs and adverse reactions. Safety was assessed by serum coagulation factors (platelets, PTT, INR) at baseline and week 12.</p> <p>Results</p> <p>After 2 months of recruitment, the eligible upper age limit was raised from 18 to 35 years of age in order to facilitate recruitment of the required sample size. Eleven participants completed the trial with 85% or greater adherence to the protocol. The total VASI score improved by 0.5 (P = 0.021) from 5.0 to 4.5, range of scale 0 (no depigmentation) to 100 (completely depigmented). The progression of vitiligo stopped in all participants; the total VASI indicated an average repigmentation of vitiligo lesions of 15%. VETF total vitiligo lesion area decreased 0.4% (P = 0.102) from 5.9 to 5.6 from baseline to week 12. VETF staging score improved by 0.7 (P = 0.101) from 6.6 to 5.8, and the VETF spreading score improved by 3.9 (P < 0.001)) from 2.7 to -1.2. There were no statistically significant changes in platelet count, PTT, or INR.</p> <p>Conclusions</p> <p>The criteria for feasibility were met after increasing the maximum age limit of the successful recruitment criterion; participant retention, safety and effectiveness criteria were also met. Ingestion of 60 mg of <it>Ginkgo biloba </it>BID was associated with a significant improvement in total VASI vitiligo measures and VETF spread, and a trend towards improvement on VETF measures of vitiligo lesion area and staging. Larger, randomized double-blind clinical studies are warranted and appear feasible.</p> <p>Trial Registration</p> <p>Clinical trials.gov registration number <a href="http://www.clinicaltrials.gov/ct2/show/NCT00907062">NCT00907062</a></p

ASHTABULA SUCCESSES--MACRO NOW OR FOREVER HOLD YOUR PIECES!

As facility demolition and remediation continued at the DOE Ashtabula Environmental Management Project (AEMP), a DOE closure site located in Ashtabula, OH, the quantity of mixed waste increased by approximately twenty-fold from the original Site Treatment Plan estimates to over 567 m3 (20,000 cubic feet). Also, a greater variety of low-level mixed waste (MW) was identified that was suitable for alternate debris treatment like macroencapsulation (MACRO) instead of traditional shredding, stabilization, and solidification to improve the overall safety and cost-effectiveness. Macroencapsulation is required for lead and authorized for hazardous debris under the alternate debris treatment standards per 40 CFR 268.45. Several polymer encapsulation processes were being explored, developed, and deployed in the mid-1990's by various groups including the DOE Mixed Waste Focus Area, DOE EM-50 Office of Science and Technology, Brookhaven National Laboratory, DOE Macro Working Group, DOE-Albuquerque Mixed Waste/Mobile Treatment Unit, and Envirocare of Utah, Inc. As a result, technically-proven macroencapsulation and microencapsulation processes using extruded polyethylene beads were verified as being technically acceptable for waste treatment to RCRA standards. The AEMP had a variety of waste forms where technically-proven systems were needed to perform on-site treatment of challenging mixed wastes (MW) from production operations (i.e. HEPA filters, barium salt contaminated steel) containing high concentrations of enriched uranium, graphite, salts, and RCRA metals. The AEMP continued with a technology development and deployment process to license, permit, install, and safely operate two proven polymer encapsulation systems for both RCRA microencapsulation and RCRA macroencapsulation using surplus DOE equipment from Rocky Flats to establish cost-effective mobile treatment capability. The AEMP treated approximately 16 m3 (= 579 cf) of challenging mixed wastes onsite at approximately 50 wt% waste loading using polymer microencapsulation and macroencapsulation systems to isolate the hazards from the general public. These wastes were then profiled and buried in fifty-seven (57) containers containing approximately 33 m3 (1,194 cf) of LDR-compliant wastes at NTS and Envirocare of Utah, Inc. However, this paper summarizes only the MACRO technology approval, waste inspection/treatment/certification process, and technology transfer as deployed at AEMP and Sandia National Laboratories (SNL). It describes only the sequences associated with optimizing the process for the polymer MACRO system to meet overall DOE waste management needs. AEMP performed MACRO on 4 m3 (139 cf) of RCRA debris before the system was shut down. The shut down occurred due to new project direction, funding availability, and alternate offsite treatment capabilities at TSCAI and/or commercial facilities for the balance of the mixed wastes

Follow-up examinations for melanoma: New aspects

The primary goal of follow-up examinations in cutaneous melanoma is to detect development of second melanomas or tumor recurrences in an early phase of development. Early detection of recurrences has prognostic impact for the patients. More than 80% of all recurrences are primarily detected during follow-up examinations when a structured stage-adapted schedule is applied. In the majority of cases, recurrences are detected by physical examinations. Lymph node ultrasound enables early detection of locoregional recurrences before they become palpable and represents a sensitive examination method. Further imaging techniques in primary tumors are dispensable. In primary melanomas and particularly in those with a tumor thickness of less than 1 mm a reduction of the kind and frequency of technical examinations can be recommended according to recent publications. Hence the costs of follow-up examinations can be reduced clearly without increased risk for the patients. In stage III patients an intensified schedule including imaging techniques can help in increasing the early detection of recurrences