How can we effectively address the paraneoplastic dermatomyositis: Diagnosis, risk factors and treatment options

Purpose: Dermatomyositis (DM) represents an auto-immune inflammatory myopathy. In this review, we analyzed the incidence of DM as a clinical manifestation highlighting the peculiar clinical and treatment characteristics of this disease when occurring in the context of different malignancies. Methods: A systematic literature review was performed based on database search in PubMed/Medline and included English articles until December 2016. Results: In up to 20% of cases DM appears as a paraneoplastic syndrome associated with multiple malignancies such as ovarian, breast, prostate, lung, nasopharyngeal and colorectal cancer, and non-Hodgkin lymphomas. It can be presented either before, in the time, or after cancer diagnosis. Systemic sclerosis and mixed connective-tissue disease represent common coinciding disorders. Particular caution should be given in the radiotherapy because the microvascular endothelial radiation damage and autoimmune inflammatory collagen vascular disease caused by DM may be additive. There is a higher risk of late toxicity in the presence of other concurrent vascular diseases, including diabetes, hypertension or administration of chemotherapy. Prednisone represents the first-line treatment option but immunosuppressive drugs such as azathioprine and methotrexate may also be incorporated in the therapeutic armamentarium especially when DM is associated with malignancy. Intravenous immunoglobulin could be a promising alternative in prednisone-resistant cases. The effectiveness of therapies with antigen-specific agents such as monoclonal antibodies is currently under investigation. Conclusions: Timely diagnosis coupled with a treatment plan focused on muscular endurance and improvement of skin lesions and other symptoms offer a favorable response to therapy along with the achievement of a higher quality of life for these patients. © 2017 Zerbinis Publications. All rights reserved

The role of statins in prevention of preeclampsia: A promise for the future?

Preeclampsia has been linked to high morbidity and mortality during pregnancy. However, no efficient pharmacological options for the prevention of this condition are currently available. Preeclampsia is thought to share several pathophysiologic mechanisms with cardiovascular disease, which has led to investigations for the potential role of statins (HMG CoA reductase inhibitors) in its prevention and early management. Pravastatin seems to have a safer pharmacokinetic profile compared to other statins, however, the existing preclinical evidence for its effectiveness in preeclampsia treatment has been mostly restricted to animal models. This review aims to summarize the current data and delineate the potential future role of statins in the prevention and management of preeclampsia. © 2017 Katsi, Georgountzos, Kallistratos, Zerdes, Makris, Manolis, Nihoyannopoulos and Tousoulis

Addressing the post-irradiation hypothalamic-pituitary endocrine abnormalities of brain tumors in pediatric patients

Purpose: Hypothalamic-pituitary axis is susceptible to radiotherapy, causing endocrine disorders to childhood cancer survivors. We conducted a systematic review in order to assess the radiation-induced toxicity that leads to hormone secretion abnormalities and their severity in children with brain tumors. Methods: The data were collected by relevant studies on PubMed and EMBASE. Articles up to December 2016 were included. We selected studies which focused on children patients (<18 yr old) with brain tumors treated with radiotherapy and the consequences for their endocrine system. Results: Growth hormone (GH) deficiency was the most common post-irradiation abnormality among children cancer survivors, followed by gonadotrophin (GT), thyroid stimulating hormone (TSH), corticotropin (ACTH) and prolactin (PRL) disorders. Conclusions: The age of the patient, total radiotherapy dose, number of fractions, fraction size and the duration of treatment seem to determine the severity of these disturbances. © 2017 Zerbinis Publications. All rights reserved

Prognostic role of serum thymidine kinase 1 kinetics during neoadjuvant chemotherapy for early breast cancer

BACKGROUND: Emerging data support the use of thymidine kinase 1 (TK1) activity as a prognostic marker and for monitoring of response in breast cancer (BC). The long-term prognostic value of TK1 kinetics during neoadjuvant chemotherapy is unclear, which this study aimed to elucidate. METHODS: Material from patients enrolled to the single-arm prospective PROMIX trial of neoadjuvant epirubicin, docetaxel and bevacizumab for early BC was used. Ki67 in baseline biopsies was assessed both centrally and by automated digital imaging analysis. TK1 activity was measured from blood samples obtained at baseline and following two cycles of chemotherapy. The associations of TK1 and its kinetics as well as Ki67 with event-free survival and overall survival (OS) were evaluated using multivariable Cox regression models. RESULTS: Central Ki67 counting had excellent correlation with the results of digital image analysis (r = 0.814), but not with the diagnostic samples (r = 0.234), while it was independently prognostic for worse OS [adjusted hazard ratio (HRadj) = 2.72, 95% confidence interval (CI) 1.19-6.21, P = 0.02]. Greater increase in TK1 activity after two cycles of chemotherapy resulted in improved event-free survival (HRadj = 0.50, 95% CI 0.26-0.97, P = 0.04) and OS (HRadj = 0.46, 95% CI 0.95, P = 0.04). There was significant interaction between the prognostic value of TK1 kinetics and Ki67 (pinteraction 0.04). CONCLUSION: Serial measurement of serum TK1 activity during neoadjuvant chemotherapy provides long-term prognostic information in BC patients. The ease of obtaining serial samples for TK1 assessment motivates further evaluation in larger studies