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Abstract: Background: Electrochemotherapy (ECT) is currently used to treat unresectable superficial tumours of different histotypes through the combination of cytotoxic chemotherapy and local application of electric pulses. In 2006, a collaborative project defined the ESOPE (European Standard Operating Procedures of Electrochemotherapy) guidelines to standardize the procedure. The International Network for Sharing Practices of Electrochemotherapy (InspECT) aims to refine the ESOPE and improve clinical practice. Limiting patient exposure to systemic chemotherapy would be advisable to ameliorate ECT safety profile. Objective: The aim of this study was to evaluate the efficacy and toxicity of ECT with reduced chemotherapy dosages. Methods: In a retrospective analysis of a prospectively maintained database (InspECT registry), we evaluated the outcome of patients who received ECT with reduced dosages of bleomycin (7500, 10 000 or 13 500 IU/m2, instead of the standard dose of 15 000 IU/m2). Tumour response in melanoma patients was compared with melanoma patients of the InspECT registry who received the standard dose of bleomycin. Results: We identified 57 patients with 147 tumours (melanoma, 38.6%; squamous cell carcinoma, 22.8%; basal cell carcinoma, 17.5%; breast cancer 7%; Kaposi sarcoma 7%; other histotypes, 7.1%). Per‐tumour complete response (CR) rate at 60 days was 70.1% (partial, 16.3%); per‐patient CR was 57.9% (partial, 21.1%). Local pain was the most frequently reported side‐effect (n = 22 patients [39%]), mostly mild; two patients experienced flu‐like symptoms, one patient nausea. We observed the same CR rate (55%) in patients with melanoma treated by reduced or conventional bleomycin dosages (P = 1.00). Conclusions: Electrochemotherapy performed with reduced bleomycin dosages could be as effective as with currently recommended dose. Patients with impaired renal function or candidate to multiple ECT cycles could benefit from a reduced dose protocol. Our findings need prospective confirmation before being adopted in clinical practice. [ABSTRACT FROM AUTHOR]

Background ( ECT) is an effective local treatment for cutaneous metastasis. Treatment involves the administration of chemotherapeutic drugs followed by delivery of electrical pulses to the tumour. Objectives To investigate the effectiveness of ECT in cutaneous metastases of melanoma and to identify factors that affect (beneficially or adversely) the outcome. Methods Thirteen cancer centres in the International Network for Sharing Practices on Electrochemotherapy consecutively and prospectively uploaded data to a common database. ECT consisted of intratumoral or intravenous injection of bleomycin, followed by application of electric pulses under local or general anaesthesia. Results In total, 151 patients with metastatic melanoma were identified from the database, 114 of whom had follow-up data of 60 days or more. Eighty-four of these patients (74%) experienced an overall response ( OR = complete response + partial response). Overall, 394 lesions were treated, of which 306 (78%) showed OR, with 229 showing complete response (58%). In multivariate analysis, factors positively associated with overall response were coverage of deep margins, absence of visceral metastases, presence of lymphoedema and treatment of nonirradiated areas. Factors significantly associated with complete response to ECT treatment were coverage of deep margins, previous irradiation of the treated area and tumour size (< 3 cm). One-year overall survival in this cohort of patients was 67% (95% confidence interval 57-77%), while melanoma-specific survival was 74% (95% confidence interval 64-84%). No serious adverse events were reported, and the treatment was in general very well tolerated. Conclusions ECT is a highly effective local treatment for melanoma metastases in the skin, with no severe adverse effects noted in this study. In the presence of certain clinical factors, ECT may be considered for local tumour control as an alternative to established local treatments, or as an adjunct to systemic treatments. [ABSTRACT FROM AUTHOR]

Supplementation with carotenoids is proposed to protect against age-related macular degeneration. There is, however, considerable variability in retinal macular pigment response, which may be due to underlying genetic variation. The purpose of this study was to determine whether genetic factors, which have been previously associated with cross-sectional macular pigment levels in the retina or serum lutein, also influence response to supplementation. To this end we conducted an association study in 310 subjects from the TwinsUK cohort between variants in 8 candidate genes and serum lutein and retinal macular pigment optical density (MPOD) levels before and after supplementation. Four variants were associated with MPOD response to supplementation (p < 0.05): rs11057841 (SCARB1), rs4926339 (RPE65), rs1929841 (ABCA1) and rs174534 (FADS1). We also confirmed previous associations between rs6564851 near BMCO1 (p < 0.001) and rs11057841 within SCARB1 (p = 0.01) and baseline measures of serum lutein; while the latter was also associated with MPOD response, none of the BMCO1 variants were. Finally, there was evidence for association between variants near RPE65 and ELOVL2 and changes in lutein concentration after supplementation. This study is the first to show association between genetic variants and response to carotenoids supplementation. Our findings suggest an important link between MP response and the biological processes of carotenoids transport and fatty acid metabolism., (Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: To determine the efficacy and safety of different doses of secukinumab, a fully human monoclonal antibody for targeted interleukin-17A blockade, in patients with noninfectious uveitis., Design: Three multicenter, randomized, double-masked, placebo-controlled, dose-ranging phase III studies: SHIELD, INSURE, and ENDURE., Participants: A total of 118 patients with Behçet's uveitis (SHIELD study); 31 patients with active, noninfectious, non-Behçet's uveitis (INSURE study); and 125 patients with quiescent, noninfectious, non-Behçet's uveitis (ENDURE study) were enrolled., Methods: After an initial subcutaneous (s.c.) loading phase in each treatment arm, patients received s.c. maintenance therapy with secukinumab 300 mg every 2 weeks (q2w), secukinumab 300 mg monthly (q4w), or placebo in the SHIELD study; secukinumab 300 mg q2w, secukinumab 300 mg q4w, secukinumab 150 mg q4w, or placebo in the INSURE study; or secukinumab 300 mg q2w, secukinumab 300 mg q4w, secukinumab 150 mg q4w, or placebo in the ENDURE study., Main Outcome Measures: Reduction of uveitis recurrence or vitreous haze score during withdrawal of concomitant immunosuppressive medication (ISM). Other end points included best-corrected visual acuity, ISM use (expressed as a standardized ISM score), and safety outcomes., Results: After completion or early termination of each trial, there were no statistically significant differences in uveitis recurrence between the secukinumab treatment groups and placebo groups in any study. Secukinumab was associated with a significant reduction in mean total post-baseline ISM score (P = 0.019; 300 mg q4w vs. placebo) in the SHIELD study. Likewise, secukinumab was associated with a greater median reduction in ISM score versus placebo in the INSURE study, although no statistical analysis of the difference was conducted because of the small sample size. Overall, there was no loss in visual acuity reported in any treatment group during follow-up in all 3 studies. According to descriptive safety statistics, the frequencies of ocular and nonocular adverse events seemed to be slightly higher among secukinumab groups versus placebo across the 3 studies., Conclusions: The primary efficacy end points of the 3 studies were not met. The secondary efficacy data from these studies suggest a beneficial effect of secukinumab in reducing the use of concomitant ISM., (Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Infantile haemangioma is the commonest childhood tumour and approximately 10% requires treatment.(1,2) Recent reports have highlighted the impressive efficacy of propranolol in treating rapidly proliferating haemangioma. The aims of our study were to prospectively assess the efficacy of propranolol as a first line treatment for problematic haemangioma, and develop a treatment regime. 31 consecutive patients with rapidly proliferating infantile haemangioma with functional impairment or cosmetic disfigurement were treated with propranolol as a first line treatment. All patients had cardiovascular pre-treatment work-up and commenced on propranolol at 3 mg/kg/day. A rapid halt in haemangioma proliferation was seen in 100% of patients and significant regression in 87% of patients. This treatment is well tolerated and has little side effects. Since this study, our unit has adopted the policy of using propranolol as a first line treatment for all problematic proliferative infantile haemangiomas., (Copyright © 2010 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Seed of Mucuna pruriens (Velvet beans) has been prescribed by traditional medicine practitioners in Nigeria as a prophylactic oral antisnake remedy. In the present studies, we investigated the protective effects of M. pruriens seed extract (MPE) against histopathological changes induced by intravenous injection of Naja sputatrix (Malayan cobra) venom in rats pretreated with the seed extract. Examination by light microscope revealed that the venom induced histopathological changes in heart and blood vessels in liver, but no effect on brain, lung, kidney and spleen. The induced changes were prevented by pretreatment of the rats with MPE. Our results suggest that MPE pretreatment protects rat heart and liver blood vessels against cobra venom-induced damages.

Macular pigment (MP) has been suggested to have a protective role in age-related macular degeneration by reducing the amount of oxidative stress on the retina. MP levels peak at the foveal center, where it is found predominantly in the receptor axon and inner plexiform layers of the retina. The purpose of this study was to investigate the relationship between central retinal thickness and macular pigment optical density in a group of healthy subjects. We report that macular pigment optical density (MPOD) has a significant and positive relationship with central retinal thickness as measured by optical coherence tomography. The strength of the observed relationship (r approximately 0.30) was independent of the technique used to measure MPOD, whether heterochromatic flicker photometry (HFP) or 2-wavelength autofluorescence (AF). Of note, there was no statistically demonstrable relationship between MPOD at an eccentricity of 1- or 2-degrees and central retinal thickness. This finding has important implications for future studies investigating MPOD, and its response to dietary modification/supplementation.

This paper describes the long term results of a surgical technique used for correction of syndactyly. This technique has been practised by the senior author since 1987 and was published in 1990. The technique involves the use of a dorsal trilobed flap for the reconstruction of the commissure and zig-zag incisions for the fingers. This technique does not require the use of skin grafts. This technique has been used in 62 webs in 44 patients. In this total group, there were 30 patients of primary hand syndactyly with 40 webs. Seventeen patients of primary syndactyly with 25 webs were followed up. The follow-up of these patients ranged from 2 years to 12 years. The long term results reveal a simple, effective technique which does not require the use of skin grafts, and is associated with good functional and far superior cosmetic results.

In ruby laser-assisted hair removal, microscopic damage is often seen in the basal epidermal cells, where melanosomes are concentrated. It is not known whether this treatment leads to cellular hyperproliferation. It was the aim of this study to investigate this. Ten white patients were treated with the Chromos 694-nm Depilation Ruby Laser, and biopsies taken before and after treatments to assess the presence of cell hyperproliferation, which normally accompanies epidermal damage, with immunohistochemical staining of keratin 16 and Ki67. No evidence of cell hyperproliferation was seen in all specimens examined after ruby laser irradiation. The authors conclude that despite the possible microscopic damages seen in the basal epidermis after laser hair removal, there is no evidence of cellular hyperproliferation. This is in contrast to ultraviolet-irradiated cell damage, in which increased basal cell turnover is seen.

Despite widespread demand for efficient, reliable methods of eliminating unwanted hair from the face and body, available options were limited until the recent development of laser-assisted hair removal systems. This is a review of the various types of hair removal methods available today with an emphasis on laser-assisted hair removal.

Ruby laser-assisted hair removal is thought to work via selective photothermolysis, which relies on light reaching the deeper layers of skin, and the absorption of light by the target chromophore, melanin. It is therefore possible that efficacy of treatment is affected by anatomic factors that determine the amount of light reaching the hair bulbs (i.e., skin color, depth of intracutaneous hair, epidermal thickness and dermal density) and the melanin content of hair. To examine this hypothesis, a prospective study was performed. Forty-eight volunteers were treated with the Chromos 694 Depilation Ruby Laser at a single standard fluence of 11 J/cm2. Treatment efficacy was determined by measuring hair density at 3 and 7 months after treatment. Epidermal depth and dermal density were measured from 2-mm biopsies taken before treatment, and the intracutaneous hair length was determined from plucked hair. Skin color was assessed using a spectrophotometer, and melanin content of dissolved hair was assessed using spectrophotometry. Efficacy of treatment for each patient was compared with the patient's age, intracutaneous hair length, epidermal depth, dermal density, skin color, and total melanin content and relative eumelanin content of hair. No correlation was found between the efficacy of treatment and age and the various anatomic factors. Patients with higher eumelanin content in their hair had better long-term results (Spearman rank test, p = 0.00219). The results suggested that the efficacy of treatment did not depend solely on the amount of laser light penetrating the skin but correlated well with the eumelanin content of hair. The clinical implication of this finding is discussed.

A ruby laser has been developed to remove unwanted hair. Melanin within the hair is used as a natural chromophore. It is postulated that photothermal damage destroys the hair itself and also key cells surrounding the hair follicle to prevent regrowth. A prospective study of laser depilation in 116 patients or 175 sites was performed over a period of 18 months. All the patients had tried other methods of hair removal and found them to be unsatisfactory. Hair counts (follicles/cm2) were used to judge the outcome. The mean follow-up time was 23.25 weeks (range 12-76 weeks). After a mean number of treatments of 1.92 (range 1-20) there was a 56.4% reduction in hair density. Comparing pre- and post-treatment hair density, there was a highly significant reduction (paired t-test: P < 0.00001). Laser removal of hair is now a realistic treatment option.

An unpredictable response, even in patients with dark hair, often undermines successful ruby laser hair removal. A prospective clinical study was carried out to evaluate the roles of melanin content and growth phases of hair in treatment efficacy. Thirty-six volunteers with white skin and dark hair were recruited for the study, and were all treated using the Chromos 694 Depilation Ruby Laser. The overall efficacy of treatment was assessed at the end of 3 months. The efficacy of laser treatment is not due solely to the proportion of hair in the growing or static phase of the hair cycle. There is a lack of correlation between the melanin content and the overall efficacy of laser hair removal in those treated once, but patients with darker hair responded better after repeated treatments. The proportion of hair in the growth phase and the melanin content of hair do not contribute solely to the efficacy of ruby laser hair removal.

Several clinical studies on the efficacy of ruby laser-assisted hair removal have reported that regrowth of hair after treatment is common. One of the reasons for the regrowth of hair is the incomplete destruction of germinative hair cells due to the insufficient penetration of the ruby laser in the skin. It was the aim of this study to estimate the extent of damage to the hair follicles after one ruby laser treatment and to determine whether the ruby laser destroyed the bulbs and the bulge regions of hair follicles. The extent of laser damage in hair shafts was determined by serial examination of six specimens of ex vivo scalp skin lasered with the Chromos 694 Depilation Ruby Laser at 14 J per square centimeter and 20 J per square centimeter. Another nine specimens of ex vivo scalp skin were similarly lasered, and monoclonal antibody LP2K was used to identify the bulge regions of the hair follicles using the immunoperoxidase technique. Damage to the bulge region was assessed from consecutive specimens, which were stained with hematoxylin-eosin stain. The mean depth of laser damage sustained by hair follicles was 1.34 mm (14 J per square centimeter) and 1.49 mm (20 J per square centimeter) underneath the skin surface. Most of the laser damage involved the bulge regions but fell short of the hair bulbs. The laser damage did not seem to extend far enough down the hair shafts to result in permanent hair destruction. The clinical implications of this finding are discussed.

The majority of splenic cysts occur as a result of parasitic infection, most commonly in countries where hydatid disease is endemic. In the Western world however, their occurrence is extremely rare and aetiology less clear. Approximately 800 cases of non-parasitic splenic cysts have been reported in the world literature to date. Their presentation ranges from that of an incidental finding on abdominal examination to catastrophic intraperitoneal haemorrhage. The methods of treatment of splenic cysts are protean with no universally accepted policy. We report a case of a massive splenic cyst in an adolescent female treated by partial splenectomy. We also present a review of the pertinent literature on this subject paying special attention to the role of conservative surgery with preservation of normal splenic tissue.

Three cases of the localized form of congenital generalized fibromatosis are described in females under one year. The lesions were in the parotid region, biceps muscle and abdominal wall. The infiltrative or nodular pattern of these tumours with the periphery resembling smooth muscle and the central portion resembling a haemangiopericytoma makes them a distinct histological entity. Ultrastructurally, these tumours are composed of myofibroblasts. The differential diagnosis from other soft tissue tumours in infancy and early childhood is discussed. These tumours are benign and recurrence after complete local excision is rare.