Adherence to treatment guidelines for melanoma as a measure of quality care

Introduction: Melanoma, a malignancy of melanocytes, is the most deadly and aggressive form of skin cancer. Although science has led to much advancement in melanoma treatment, significant disparities and practice variation exist in the United States. The objective of this study are to: examine National Comprehensive Cancer Network (NCCN) guidelines adherence rates in the state of California, determine what patient and provider level characteristics predict receiving NCCN adherent care, and to measure the association between guideline directed treatment and improved patient outcomes. Methods: This is a retrospective, population-based study of invasive melanoma diagnosed between 2000 and 2006, using the California Cancer Registry (CCR). Patients were classified as having received NCCN adherent or non-adherent treatment. Multivariate analysis was used to identify patient and provider characteristics associated with non-adherence. Finally, melanoma specific and overall survival was analyzed. Results: A total of 29,533 patient cases were analyzed. NCCN recommended treatment for both surgical margins and lymph procedures was achieved in 73.2% of patient cases. Adherence to surgical margins was observed in 84.8% of all patient cases and lymph node adherence was 61%. NCCN Surgical guidelines were correlated with improved survival. Conclusion: Compliance with NCCN guidelines is suboptimal in California, especially regarding lymph node procedures. Patients with more advanced stage, difficult tumor location, treated by less experienced physicians, of non-white race, with non-private insurance and advanced age had a higher risk of non-adherent treatment. NCCN guidelines are correlated with improved survival and represent a valid measure of quality for patients diagnosed with melanoma

Immunohistochemistry of angiogenesis mediators before and after pulsed dye laser treatment of angiomas.

Tissue effects of vascular lesion laser treatment are incompletely understood. Injury caused by pulsed dye laser (PDL) treatment may result in altered expression of mediators associated with angiogenesis.Eight human subjects had one angioma treated with PDL (7 mm, 1.5 millisecond pulse duration, 9 J/cm(2), cryogen spray cooling of 30 millisecond with a 30 millisecond delay). One week later, three biopsies were taken: normal skin, untreated angioma, angioma post-PDL. Tissue was frozen and sections processed for immunohistochemistry staining of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), matrix metalloproteinase 9 (MMP-9), and angiopoietin 2 (ANG-2). Images were graded in a blinded fashion by a board certified dermatopathologist.There were no clear trends in VEGF expression in the epidermis, dermis, or endothelial cells. As compared to normal skin, angiomas demonstrated the following: bFGF was decreased in the epidermis; MMP-9 was decreased or unchanged in the epidermis and increased in the endothelial cells; ANG-2 was increased in the endothelial cells. When comparing normal skin to angiomas + PDL, bFGF was decreased in the epidermis and increased in the dermis; MMP-9 was decreased or unchanged in the epidermis; ANG-2 was again increased in the endothelial cells. Comparison of staining in angioma to angioma + PDL samples revealed increased dermal bFGF expression.Alterations in angiogenesis mediators were noted after PDL. Angiogenesis mediator changes associated with PDL treatment differed from those previously reported for incisional biopsies. This pilot study can guide future work on laser-induced alterations in vascular lesions and such information may ultimately be used to optimize treatment outcomes

Mitochondrial DNA Variants Mediate Energy Production and Expression Levels for CFH, C3 and EFEMP1 Genes: Implications for Age-Related Macular Degeneration

BACKGROUND: Mitochondrial dysfunction is associated with the development and progression of age-related macular degeneration (AMD). Recent studies using populations from the United States and Australia have demonstrated that AMD is associated with mitochondrial (mt) DNA haplogroups (as defined by combinations of mtDNA polymorphisms) that represent Northern European Caucasians. The aim of this study was to use the cytoplasmic hybrid (cybrid) model to investigate the molecular and biological functional consequences that occur when comparing the mtDNA H haplogroup (protective for AMD) versus J haplogroup (high risk for AMD). METHODOLOGY/PRINCIPAL FINDINGS: Cybrids were created by introducing mitochondria from individuals with either H or J haplogroups into a human retinal epithelial cell line (ARPE-19) that was devoid of mitochondrial DNA (Rho0). In cybrid lines, all of the cells carry the same nuclear genes but vary in mtDNA content. The J cybrids had significantly lower levels of ATP and reactive oxygen/nitrogen species production, but increased lactate levels and rates of growth. Q-PCR analyses showed J cybrids had decreased expressions for CFH, C3, and EFEMP1 genes, high risk genes for AMD, and higher expression for MYO7A, a gene associated with retinal degeneration in Usher type IB syndrome. The H and J cybrids also have comparatively altered expression of nuclear genes involved in pathways for cell signaling, inflammation, and metabolism. CONCLUSION/SIGNIFICANCE: Our findings demonstrate that mtDNA haplogroup variants mediate not only energy production and cell growth, but also cell signaling for major molecular pathways. These data support the hypothesis that mtDNA variants play important roles in numerous cellular functions and disease processes, including AMD

The H cybrid versus J cybrid cultures show differences in the ATP production and lactate levels.

<p><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0054339#pone-0054339-g003" target="_blank"><b>Figure 3a</b></a><b>.</b> Relative ATP levels in H versus J cybrid cultures at three different cell concentrations incubated for 24 hours. The H cybrids produced increased ATP levels compared to J cybrid cultures (***p<0.001). <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0054339#pone-0054339-g003" target="_blank">Figure 3b</a>. Lactate levels in cybrid H versus cybrid J cultures at two different cell concentrations incubated for 24 hours. The H cybrids had decreased lactate production when compared to the J cybrids (**p<0.01, ***p<0.001) indicating lower glycolysis activity. Cybd, cybrid.</p