Does the time interval between sentinel lymph node biopsy and completion lymph node dissection affect outcome in malignant melanoma? A retrospective cohort study.

Nodal clearance was recommended after positive sentinel lymph node biopsy (SLNB) despite further metastases to the regional lymph node basin being found in only 6-21% in the literature. This retrospective study was conducted to determine the role of the time interval between excision of primary melanoma and confirmed metastasis in the sentinel lymph node biopsy as well as the one between positive sentinel lymph node biopsy (SLNB-positive patients) and subsequent completion lymph node dissection (CLND) on the presence of metastases. The monocentric analysis included 121 patients with a history of completion lymph node dissection after positive SLNB from January 2005 to October 2013. Additional metastases in the regional lymph node basin (non-sentinels) were found in 14.05% (n = 17). Significant risk factors for the presence of metastases in CLND were the time between confirmed primary tumour to metastasis in sentinel lymph nodes (SLN) (p = 0.0034), N-category of TNM-classification (p = 0.0066) and independent of thickness of primary tumour (p = 0.11). If SLNB was performed up to forty-three days after confirmed primary melanoma, subsequent lymph node dissection was positive in less than 9.1%. When SLNB was performed with a delay of more than 80 days, all patients had metastases in the CLND specimens. Our data analysis suggests that delays in subsequent procedures of SLNB after diagnosis of primary melanoma may have a greater impact on positivity of non-sentinel lymph nodes than previously assumed. Our retrospective analysis may indicate the reconsideration of time schedule in the management of primary melanoma to potentially avoid local relapse in the draining lymph node region after positive SLNB.

Problems and challenges of predatory journals.

The companies publishing predatory journals are an emerging problem in the area of scientific literature as they only seek to drain money from authors without providing any customer service for the authors or their readership. These predatory journals try to attract new submissions by aggressive email advertising and high acceptance rates. But in turn, they do not provide proper peer review, and therefore, the scientific quality of submitted articles is questionable. This is important because more and more people, including patients, are reading such journals and rely on the information they provide. Consequently, predatory journals are a serious threat to the integrity of medical science, and it is crucial for scientists, physicians and even patients to be aware of this problem. In this review, we briefly summarize the history of the open access movement, as well as the rise of and roles played by predatory journals. In conclusion, young and inexperienced authors publishing in a predatory journal must be aware of the damage of their reputation, of inadequate peer review processes and that unprofitable journals might get closed and all published articles in that journal might be lost.

Effects of Vitamin D3 on asymmetric- and symmetric dimethylarginine in arterial hypertension.

BACKGROUND AND AIMS: Accumulating evidence has proposed a correlation between vitamin D (25(OH)D) insufficiency and cardiovascular (CV) disease. Vitamin D associated effects on endothelial function have been suggested to be a possible culprit. The present study investigated the association of vitamin D3 treatment on markers of endothelial dysfunction in patients with arterial hypertension. METHODS AND RESULTS: The Styrian Vitamin D Hypertension Trial is a double-blind, placebo-controlled, single-centre study conducted at the Medical University of Graz, Austria. A total of 200 study participants with arterial hypertension and 25(OH)D levels below 30ng/mL were enrolled. The study participants were randomized to receive 2800 IU of vitamin D3 per day as oily drops (n=100) or placebo (n=100) for a duration of eight weeks. The present study uses an analysis of covariance (ANCOVA) to investigate the effect of vitamin D3 treatment on symmetric (SDMA) and asymmetric dimethylarginine (ADMA). A total of 187 participants (mean [SD] age 60.0 [11.3] years; 47% women; 25(OH)D 21.2 [5.6]ng/mL; mean systolic blood pressure of 131.4 [8.9] mmHg on a median of 2 antihypertensive drugs) completed the trial. Mean treatment effect was -0.004 (95%CI [-0.03 to 0.04]; P=0.819) on ADMA and 0.001 (95%CI [-0.05 to 0.05]; P=0.850) on SDMA. In the subgroup analysis patients with a 25(OH)D concentration <20ng/mL had a significant increase in their log l-arginine/ADMA ratio (mean treatment effect 18.4 95%CI [1.84-34.9]µmol/L/µmol/L; P=0.030). ClinicalTrials.gov Identifier: NCT02136771 EudraCT number: 2009-018125-70 CONCLUSIONS: Vitamin D3 supplementation in hypertensive patients with low 25-hydroxyvitamin D has no significant effect on ADMA and SDMA.

Beyond the BRAFV600E hotspot: biology and clinical implications of rare BRAF gene mutations in melanoma patients.

BRAF gene mutations can be found in approximately 50% of melanomas, but the most common BRAF mutation leads to substitution at residue 600 of the protein, from valine to glutamic acid. BRAFV600E occurs in up to 95% of all melanoma cases and can be successfully blocked by using a combination of BRAF- and MEK inhibitors. The wider availability of next-generation sequencing is revealing more non-V600 BRAF mutations, and the clinical implications of these mutations are widely unknown. In this review, we will discuss the biology of the MAPK pathway and the different types of BRAF mutations as well as their effect on MEK activation. Current literature will be reviewed including in vitro data, case reports and case series.

Pregnancy as a driver for melanoma.

Whether or not pregnancy favours the occurrence and growth of melanoma is a source of controversy in the literature. Several case reports have shown dramatic courses of diseases in pregnancy. We present a case of a 36-year-old woman with multiple naevi with one melanoma detected in 2009 in the first trimester and a second primary melanoma in 2010 in the third trimester of her pregnancy. Both lesions have been present for at least 5 years and have been interpreted as dysplastic naevi. Because of their growth during pregnancy they were removed. No metastatic disease has been found between 2010 and early 2017. This case shows the difficulty of detecting melanomas in pregnancy, particularly when they mimic dysplastic naevi in women with multiple naevi, who are at higher risk. Therefore, we suggest that pregnant women with numerous naevi should be precautious of any changes of their naevi in size, shape and colour. Every suspicious lesion should be either excised or documented/monitored carefully, for example with sequential digital dermoscopy imaging.

Effects of vitamin D supplementation on glycated haemoglobin and fasting glucose levels in hypertensive patients: a randomized controlled trial.

AIM: To investigate the efficacy of vitamin D supplementation on glycaemic control. METHODS: The Styrian Vitamin D Hypertension Trial was a single-centre, double-blind, placebo-controlled study conducted between 2011 and 2014 at the Medical University of Graz, Austria. We enrolled 200 people with arterial hypertension and 25-hydroxyvitamin D [25(OH)D] concentrations <30 ng/mL. Study participants were randomized to receive either 2800 IU of vitamin D or placebo per day for 8 weeks. The present study was a post hoc analysis that incorporated an analysis of covariance (ancova) approach, while adjusting for baseline differences. RESULTS: A total of 185 participants [mean ± standard deviation age, 60.1 ± 11.3 years; 47% women; mean 25(OH)D 21.2 ± 5.6 ng/mL, mean glycated haemoglobin (HbA1c) 44.8 ± 11.8 mmol/mol and mean body mass index 30.4 ± 5.4 kg/m(2) ] completed the trial. ancova showed a mean treatment effect [95% confidence interval (CI)] on HbA1c of -3.52 (-6.7 to -0.34) mmol/mol (p = .045). There was no difference in fasting glucose -4.7 mg/dL (95% CI -16.3 to 6.9; p = .426). CONCLUSIONS: Vitamin D supplementation in obese hypertensive patients with low 25(OH)D reduces HbA1c levels. This finding warrants further investigation into potential vitamin D effects on glucose homeostasis.

Analysis of clinical, dermoscopic and histopathological features of primary melanomas of patients with metastatic disease--a retrospective study at the Department of Dermatology, Medical University of Graz, 2000-2010.

BACKGROUND: Incidence rates of malignant melanoma have been increasing worldwide and metastatic melanoma is still a significant problem despite widespread prevention programmes. OBJECTIVES: We made a systemic review of all metastasized melanoma patients treated at the Department of Dermatology, Medical University of Graz in the years 2000-2010 and looked at the kind of melanoma type, e.g. if it has been slowly growing superficial spreading melanoma (SSM) or fast growing nodular melanoma (NM). METHODS: Histological slides and clinical images of patients treated at our department between 2000 and 2010, who received chemotherapy because of proven metastatic disease were analysed with regard to growth type of their primary tumours. RESULTS: A total of 88 patients met the inclusion criteria. Mean age of all patients was 57 years (median 59 years, SD ± 15 years). Of these 88 patients 51 patients (58%) (28 male patients and 23 female patients) had SSM; mean age 58 years (median 58 years, SD ± 14 years) and 37 patients (42%) (18 male patients and 19 female patients) had NM; mean age 56 years (median 61 years, SD ± 17 years). Mean Breslow thickness in the SSM group was 2.26 mm (median: 1.6 mm, SD ± 2.11 mm). In the NM group, mean Breslow thickness was 4.59 mm (median: 3.50 mm, SD ± 4.07 mm). When separated by gender, 46 melanomas were seen in the male group (28 SSM and 18 NM) and 42 melanomas in the female group (23 SSM and 19 NM). CONCLUSIONS: Our results showed that more than half of the patients with metastatic disease had SSMs and not, as suspected, NMs. As SSMs are growing over a longer period to become invasive and potentially metastatic, there might be a chance to focus primary and secondary prevention programmes not only on fast growing tumours but also on slowly changes of tumours.

Calculated tumour volume as a prognostic parameter for survival in choroidal melanomas.

PURPOSE: Tumour diameter, tumour height, and tumour volume are considered important prognostic indicators of survival in choroidal melanomas. In this study, we investigated the prognostic impact on survival of the easily calculated volume estimate based on the assumption of a half-rotation ellipsoid. METHODS: The largest tumour diameter and tumour height were measured by ultrasound A- and B-scan in 93 patients with choroidal melanoma. Tumour volume was calculated by the half volume of a rotation ellipsoid formula, rotated around the y-axis, and compared to tumour diameter and tumour height. All parameters were correlated to the clinical outcome of the patients. RESULTS: At the time of diagnosis, the mean diameter was 10.4 mm (range 4.1-18.9 mm), and the mean height was 5.7 mm (range 1.74-14.9 mm). The range of the calculated tumour volume was between 11 and 628 mm(3) (mean volume 190 mm(3)). Among all patients, distant metastases occurred in 10 patients (10.8%). In a univariate approach using Mantel-Haenszel log-rank test, the calculated tumour volume at the time of diagnosis was the best prognostic indicator of survival followed by tumour diameter and tumour height (P=0.028). When tumour volume, horizontal and vertical tumour diameter, age, sex, and primary tumour therapy were considered in a multivariate approach using Cox proportional Hazard model, only tumour volume turned out as a significant prognostic parameter (P=0.001). CONCLUSIONS: Calculated tumour volume is a better prognostic indicator of survival of patients with choroidal melanomas than the largest tumour diameter and tumour height, and might be established in daily routine.