Time Course and Pattern of Metastasis of Cutaneous Melanoma Differ between Men and Women

Background: This study identified sex differences in progression of cutaneous melanoma. Methodology/Principal Findings: Of 7,338 patients who were diagnosed as an invasive primary CM without clinically detectable metastases from 1976 to 2008 at the University of Tuebingen in Germany, 1,078 developed subsequent metastases during follow up. The metastatic pathways were defined in these patients and analyzed using the Kaplan-Meier method. Multivariate survival analysis was performed using Cox modeling. In 18.7 % of men and 29.2 % of women (P,0.001) the first metastasis following diagnosis of primary tumor was locoregional as satellite/in-transit metastasis. The majority of men (54.0%) and women (47.6%, P = 0.035) exhibited direct regional lymph node metastasis. Direct distant metastasis from the stage of the primary tumor was observed in 27.3 % of men and 23.2 % of women (P = 0.13). Site of first metastasis was the most important prognostic factor of survival after recurrence in multivariate analysis (HR:1.3; 95 % CI: 1.0–1.6 for metastasis to the regional lymph nodes vs. satellite/in-transit recurrence, and HR:5.5; 95 % CI: 4.2–7.1 for distant metastasis vs. satellite/ in-transit recurrence, P,0.001). Median time to distant metastasis was 40.5 months (IQR, 58.75) in women and 33 months (IQR, 44.25) in men (P = 0.002). Five-year survival after distant recurrence probability was 5.2 % (95 % CI: 1.4–2.5) for men compared with 15.3 % (95 % CI: 11.1–19.5; P = 0.008) for women. Conclusions/Significance: Both, the pattern of metastatic spread with more locoregional metastasis in women, and th

Three metastatic pathways of melanoma.

<p>Pathway 1 – primary tumor, then satellite/in-transit metastases, pathway 2 – primary tumor, then regional lymph node metastasis, and pathway 3 – primary tumor, then distant metastasis. M, men; W, women.</p

Clinical and histopathological characteristics.

<p>1,078 patients (561 male and 517 female) diagnosed from 1976 to 2008 as invasive primary cutaneous melanoma who developed metastases during follow up stratified by sex and metastatic pathway.</p><p>The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding was received for this study.</p><p>ALM, acral lentiginous melanoma; IQR, interquartile range; LMM, lentigo maligna melanoma; NM, nodular melanoma; NS, not significant; SSM, superficially spreading melanoma.</p><p>Pathway 1, primary tumor, then satellite/in-transit metastases; Pathway 2, primary tumor, then regional lymph node metastasis; Pathway 3, primary tumor, then distant metastasis.</p>*<p>Pearson's χ² test.</p>†<p>Mann-Whitney test.</p

Multivariate predictors of survival after first recurrence.

<p>ALM, acral lentiginous melanoma; CI, confidence interval; HR, hazards ratio; LMM, lentigo maligna melanoma; NM, nodular melanoma; SSM, superficially spreading melanoma.</p>a<p>HR with its 95% CI.</p>b<p>Wald test significance; <i>P</i> values listed at the level of the reference categories (HR = 1.0) represent significance for the variable as a whole, all other <i>P</i> values represent significance of the category specified as compared to the reference category.</p

Survival after recurrence.

<p>Survival after recurrence in patients who progressed first to satellite/in-transit (<b>A</b>), regional lymph node (<b>B</b>), and distant metastases (<b>C</b>). <i>P</i> values are based on the log-rank test.</p

Sex differences in survival of cutaneous melanoma are age dependent: an analysis of 7338 patients

This study identified sex differences in clinical presentation and survival for primary cutaneous melanoma without clinical evidence of metastasis at diagnosis from 1976 to 2008 in southern Germany. Melanoma-specific survival curves and estimated survival probabilities were generated using the Kaplan-Meier method. Multivariate survival analyses were carried out using the Cox modeling. Male patients had significantly thicker and more frequently ulcerated tumors and a lower 10-year disease-specific survival (DSS) and recurrence-free survival probability compared with females among patients of 43 years old or younger (DSS: 86.1 vs. 93.2%, P<0.001) and 44-60 years old (DSS: 83.5 vs. 90.1%, P<0.001). The survival advantage of female patients in terms of 10-year DSS and 10-year recurrence-free survival was not observed after an age of 60 years (P=0.21 and 0.51, respectively). Sex was of prognostic importance for DSS and survival after recurrence [hazards ratio (HR): 1.3; 95% confidence interval (CI): 1.1-1.6; P=0.002 and HR: 1.2; 95% CI: 1.0-1.5; P=0.018, respectively]. Stratified by age groups, sex remained of prognostic importance for DSS only in patients of 43 years or younger, and 44-60 years old (HR: 1.5; 95% CI: 1.0-2.1; P=0.03 and HR: 1.4; 95% CI: 1.1-2.0; P=0.02, respectively). Sex is an independent prognostic factor in surviving melanoma. The sex difference in survival with a better outcome for women is confined to melanoma patients of 60 years and younger. In addition, in younger age groups, male patients present with prognostically unfavorable features of primary melanoma. A female survival advantage is also known for other solid tumors such as colon and lung cancer; however, age dependency has not been studied

Topical prebiotics/postbiotics and PRURISCORE validation in atopic dermatitis. International study of 396 patients

Aim: To investigate the efficacy and tolerability of a cream (Rilastil Xerolact PB) containing a mixture of prebiotics and postbiotics, and to validate the PRURISCORE itch scale in the management of atopic dermatitis. Methods: The study is based on 396 subjects of both sexes in three age groups (i.e., infants, children, adults) suffering from mild/moderate Atopic Dermatitis, recruited from 8 European countries and followed for 3 months. Results: The product demonstrated good efficacy combined with good/very good tolerability in all age groups. In particular, SCORAD, PRURISCORE and IGA scores decreased significantly over the course of the study. The PRURISCORE was preferred to VAS by the vast majority of patients. Conclusion: Even though the role of prebiotics and postbiotics was not formally demonstrated since these substances were part of a complex formulation, it can be reasonably stated that prebiotics and postbiotics have safety and standardization features that probiotics do not have. In addition they are authorized by regulatory authorities, whereas topical probiotics are not