The Effects of Melatonin on the Descending Pain Inhibitory System and Neural Plasticity Markers in Breast Cancer Patients Receiving Chemotherapy: Randomized, Double-Blinded, Placebo-Controlled Trial.

Background: Adjuvant chemotherapy for breast cancer (ACBC) has been associated with fatigue, pain, depressive symptoms, and disturbed sleep. And, previous studies in non-cancer patients showed that melatonin could improve the descending pain modulatory system (DPMS). We tested the hypothesis that melatonin use before and during the first cycle of ACBC is better than placebo at improving the DPMS function assessed by changes in the 0-10 Numerical Pain Scale (NPS) during the conditioned pain modulating task (CPM-task) (primary outcome). The effects of melatonin were evaluated in the following secondary endpoints: heat pain threshold (HPT), heat pain tolerance (HPTo), and neuroplasticity state assessed by serum brain-derived neurotrophic factor (BDNF), tropomyosin kinase receptor B, and S100B-protein and whether melatonin's effects on pain and neuroplasticity state are due more so to its impact on sleep quality. Methods: Thirty-six women, ages 18 to 75 years old, scheduled for their first cycle of ACBC were randomized to receive 20mg of oral melatonin (n = 18) or placebo (n = 18). The effect of treatment on the outcomes was analyzed by delta (Δ)-values (from pre to treatment end). Results: Multivariate analyses of covariance revealed that melatonin improved the function of the DPMS. The Δ-mean (SD) on the NPS (0-10) during the CPM-task in the placebo group was -1.91 [-1.81 (1.67) vs. -0.1 (1.61)], and in the melatonin group was -3.5 [-0.94 (1.61) vs. -2.29 (1.61)], and the mean difference (md) between treatment groups was 1.59 [(95% CI, 0.50 to 2.68). Melatonin's effect increased the HPTo and HPT while reducing the (Δ)-means of the serum neuroplasticity marker in placebo vs. melatonin. The Δ-BDNF is 1.87 (7.17) vs. -20.44 (17.17), respectively, and the md = 22.31 [(95% CI = 13.40 to 31.22)]; TrKB md = 0.61 [0.46 (0.17) vs. -0.15 (0.18); 95% CI = 0.49 to 0.73)] and S00B-protein md = -8.27[(2.89 (11.18) vs. -11.16 (9.75); 95% CI = -15.38 to -1.16)]. However, melatonin's effect on pain and the neuroplastic state are not due to its effect on sleep quality. Conclusions: These results suggest that oral melatonin, together with the first ACBC counteracts the dysfunction in the inhibitory DPMS and improves pain perception measures. Also, it shows that changes in the neuroplasticity state mediate the impact of melatonin on pain. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03205033.

Histopathological grading of breast ductal carcinoma in situ: validation of a web-based survey through intra-observer reproducibility analysis.

BACKGROUND: Histopathological grading diagnosis of ductal carcinoma in situ (DCIS) of the breast may be very difficult even for experts, and it is important for therapeutic decisions. The challenge may be due to the inaccurate and/or subjective application of the diagnosis criteria. The aim of this study was to investigate the intra-observer agreement between a traditional method and a developed web-based questionnaire for scoring breast DCIS. METHODS: A cross-sectional study was carried out to evaluate the diagnostic agreement of an electronic questionnaire and its point scoring system with the subjective reading of digital images for 3 different DCIS grading systems: Holland, Van Nuys and modified Black nuclear grade system. Three pathologists analyzed the same set of digitized images from 43 DCIS cases using two different web-based programs. In the first phase, they accessed a website with a newly created questionnaire and scoring system developed to allow the determination of the histological grade of the cases. After at least 6 months, the pathologists read again the same images, but without the help of the questionnaire, indicating subjectively the diagnoses. The intra-observer agreement analysis was employed to validate this innovative web-based survey. RESULTS: Overall, diagnostic reproducibility was similar for all histologic grading classification systems, with kappa values of 0.57 ± 0.10, 0.67 ± 0.09 and 0.67 ± 0.09 for Holland, Van Nuys classification and modified Black nuclear grade system respectively. Only two 2-step diagnostic disagreements were found, one for Holland and another for Van Nuys. Both cases were superestimated by the web-based survey. CONCLUSION: The diagnostic agreement between the web-based questionnaire and a traditional method, both using digital images, is moderate to good for Holland, Van Nuys and modified Black nuclear grade system. The use of a scoring point system does not appear to pose a major risk of presenting large (2-step) diagnostic disagreements. These findings indicate that the use of this point scoring system in this web-based survey to grade objectively DCIS lesions is a useful diagnostic tool.

Immediate Reconstruction with Autologous fat Transfer Following Breast-Conserving Surgery.

This study explores the technical viability of autologous fat grafting for immediate partial breast reconstruction following the primary conservative surgery for breast cancer; restoring volume, shape, and symmetry to the treated breast. We analyze the impact in relation to mammographic follow-up and the subjective degree of satisfaction with esthetic results and although we didn't have any local failure during the observation period; we understand that is too early for any kind of conclusion. From June of 2010 to July of 2011, 20 patients were selected for breast-conserving surgery (BCS) with partial breast reconstruction with autologous fat grafting performed during the same operation by the same medical team. The fat graft was injected in the subcutaneous and intraglandular breast tissue around the resected area. We performed an overcorrection, predicting a resorbing of about 30-50% of the volume grafted. All patients received the literature-based recommendations for breast cancer treatment with complementary radiotherapy. The follow-up period after the completion of radiotherapy ranged from 13 to 29 months. The average volume grafted was 121 cc and it was 2.1 times larger than the resected volume. The esthetic scores were considered very good or good in the majority of cases. Mammograms were taken every 6 months after radiotherapy and only one patient had a mammogram classified as BI-RADS 3, suggesting fat necrosis. The remaining patients were classified as BI-RADS 2. Immediate autologous fat grafting is a promising technique for partial breast reconstruction after BCS. It is associated with high patient and physician satisfaction. It is an alternative for reconstruction of small- and medium-sized breasts. This technique has the advantage that enables the reconstruction of defects in areas difficult to repair, particularly in the upper inner quadrants. It also may reduce the need for major glandular or myocutaneous flaps mobilization.

Sexual function and chemotherapy in postmenopausal women with breast cancer.

BACKGROUND: This cross-sectional, nested cohort study assessed Female Sexual Function Index (FSFI) scores in postmenopausal women with breast cancer receiving primary chemotherapy. METHODS: The FSFI questionnaire was administered to 24 postmenopausal women one month after diagnosis of breast cancer (post-diagnosis group) and one month after completion of the first cycle of primary anthracyclin-based chemotherapy (post-chemotherapy group). Scores were compared to those of 24 healthy postmenopausal women seeking routine gynecological care (control group). All patients were sexually active at the time of enrollment. Mean age was 57.29 ± 11.82 years in the breast cancer group and 52.58 ± 7.19 years in the control group. RESULTS: Scores in all domains of the FSFI instrument were significantly lower in the post-diagnosis group than in controls (-41.3%, p < 0.001). A further major reduction in FSFI scores was evident on completion of one cycle of primary chemotherapy (down 46.7% from post-diagnosis scores, p < 0.003), again in all domains. Six patients (25%) ceased all sexual relations, in a significant change from baseline (p < 0.001). After one chemotherapy cycle, a further five patients ceased sexual activity, for a total of 11 (45.8%) participants--a borderline significant difference (p = 0.063). CONCLUSION: The present study shows that female sexual function as assessed by the FSFI declines significantly at two distinct points in time: upon diagnosis of breast cancer and after administration of systemic chemotherapy.

Reproducibility of three classification systems of ductal carcinoma in situ of the breast using a web-based survey.

This study assessed the degree of diagnostic agreement among pathologists between three classification systems of ductal carcinoma in situ of the breast (DCIS). Thirteen pathologists received the same set of digitized images of microscopy of 43 DCIS cases and answered a questionnaire containing the criteria to compose the three classification systems studied: Holland, modified Lagios, and Van Nuys. A computer program was created, which organizes the information collected from each pathologist, supplying the histological grading of the cases within the three classification systems. The results were analyzed using percental agreement and the Kappa test. Diagnostic agreement for the three DCIS of the breast classification systems presented K values that varied from 0.27 to 0.37. Among the three classifications used, most agreement was for Van Nuys, showing a Kappa index of 0.37. These results matched the interobserver agreements, with Kappa indices varying from 0.13 to 0.64 for the Holland classification; 0.23 to 0.61 for the modified Lagios classification; and 0.23 to 0.74 for the Van Nuys classification. Pathologists specialized in breast pathology showed greater reproducibility for all the criteria evaluated. Comparing the three classification systems, diagnostic agreement and accuracy were rated higher for the classification of Van Nuys compared to modified Lagios and Holland.

Fisiopatologia, diagnostico e tratamento da sindrome dos ovarios policisticos na adolescencia / Physiopathology, diagnostic and treatment of polycystic ovary syndrome during adolescence

A Sindrome dos Ovarios Policisticos (SOP) e a causa mais comum de hiperandrogenismo em adolescentes do sexo feminino, sendo um dos motivos mais frequentes de consulta nesta faixa etaria. A SOP tem sido estudada...

O tratamento da acne com Isotretinoína / Acne vulgaris and isotretinoin

No presente estudo, os autores revisam aspectos atuais relacionados ao tratamento da acne vulgar através de uma análise das modalidades farmacológicas nesta entidade clínica, dando ênfase à isotretinoína, a partir de resultados recentes