Superhydrophobic lab-on-chip measures secretome protonation state and provides a personalized risk assessment of sporadic tumour.

Secretome of primary cultures is an accessible source of biological markers compared to more complex and less decipherable mixtures such as serum or plasma. The protonation state (PS) of secretome reflects the metabolism of cells and can be used for cancer early detection. Here, we demonstrate a superhydrophobic organic electrochemical device that measures PS in a drop of secretome derived from liquid biopsies. Using data from the sensor and principal component analysis (PCA), we developed algorithms able to efficiently discriminate tumour patients from non-tumour patients. We then validated the results using mass spectrometry and biochemical analysis of samples. For the 36 patients across three independent cohorts, the method identified tumour patients with high sensitivity and identification as high as 100% (no false positives) with declared subjects at-risk, for sporadic cancer onset, by intermediate values of PS. This assay could impact on cancer risk management, individual's diagnosis and/or help clarify risk in healthy populations.

Innate immunity in cutaneous melanoma.

The skin immune system is composed of a vast network of immune cells, including lymphocytes, macrophages, neutrophils, dendritic cells and Langerhans cells, which not only are involved in inflammatory responses but also contribute to homeostatic function and may participate in the various steps of carcinogenesis. Many studies support the notion that innate immunity has a key role in the development, growth and prognosis of cutaneous malignant melanoma (MM), through the release of pro- and/or anti-inflammatory cytokines and tumour growth factors. The tumour environment in a major subset of cutaneous MM shows evidence of a T cell-infiltrated phenotype, but there is less known about the presence and the phenotype of other immune system cells. Response to immunotherapy is largely correlated with the presence of T cells in the tumour microenvironment, while the regulation exerted by stromal components such as macrophages and mast cells has been less investigated. In the current report, we review the recent literature, focusing our attention on the role of macrophages, dendritic cells, mast cells and natural killer cells in orchestrating MM progression, to better understand tumour immunobiology. The identification of new therapeutic targets and the application of approaches aimed at modulating crosstalk between immune and tumour cells, could have a crucial impact on immunotherapy and result in better clinical outcome. We hope this review will be helpful in cutaneous MM research.

An unusual case of mammary Paget’s disease in a woman with psoriasis.

Mammary Paget’s disease (MPD) is a malignant breast tumor, which is characterized by intraepidermal infiltration from malignant glandular epithelial cells. Often it may include an underlying ductal carcinoma in situ or an invasive ductal carcinoma. Clinically it appears as an erythematous patch, moist or crusted, with or without desquamation that in some cases becomes ulcerated, causing infiltration and inversion of the nipple. We report the clinical case of a 60-year-old woman, treated in our department for psoriasis, presenting with erythema of nipple and areola with nipple erosion, ulceration and poor secretion. Suspecting Paget’s disease of the nipple, radiological exams (mammography and breast MRI) were performed. A biopsy for histological examination was carried out and confirmed the diagnosis of mammary Paget’s disease. MPD is sometimes difficult to diagnose both clinically and radiologically, therefore it is important to distinguish from other conditions: in literature MPD is reported in differential diagnosis with psoriasis given its similar clinical features, and in some cases MPD has been treated with topical and systemic steroids due to a wrong diagnosis. However, the concomitance, in the same individual, of mammary Paget’s disease and psoriasis has never been described.

Is the prognosis and course of acral melanoma related to site-specific clinicopathological features?

OBJECTIVE: Acral melanoma is an uncommon type of melanoma in Caucasian patients. However, acral melanoma is the most common type of melanoma in African and Asian patients. Comparison analyses between hand-acral melanoma and foot-acral melanoma have been rarely reported in the literature. Acral melanoma is an uncommon melanocytic tumor characterized by an intrinsic aggressiveness, with specific histological and clinicopathological features. Acral melanoma involves the palms, soles and sub-ungueal sites. PATIENTS AND METHODS: A total of 244 patients with acral melanoma were included in our analysis. The current study was performed in three different medical centers: Sapienza University of Rome, San Gallicano Institute of Rome and University of Magna Graecia (Italy). The Kaplan-Meier product was used to estimate survival curves for disease-free survival and overall survival. The log-rank test was used to evaluate differences between the survival curves. Assuming that the effects of the predictor variables are constant over time, the independent predictive factors were assessed by Spearman's test and subsequently data were analyzed performing Cox proportional-hazard regression. RESULTS: In both univariate and multivariate analyses Breslow thickness (p < 0.0001) and ulceration (p = 0.003) remained the main predictors. General BRAF mutation was detected in 13.8% of cases. We found that median Breslow value and the percentage of recurrences were similar in hand-acral melanoma and foot-acral melanoma, as well as there were no differences in both short and long-term. CONCLUSIONS: The absence of differences in survival between hand-acral melanoma and foot-acral melanoma shows that the aggressiveness of the disease is related to distinct mutational rate, as well as to anatomical site-specific features, rather than to the visibility of the primary lesion.

Improvement of survival in patients with melanoma and non-melanoma skin cancers compared to patients without double cutaneous malignancies.

OBJECTIVE: The worldwide incidence of cutaneous malignant melanoma (MM) has been rising steadily over the past 30 years. At the same time non-melanoma skin cancers (NMSC) are the most prevalent type of cancer in United States and Europe. Up to date, no paper has explored the influence on the general survival in patients with MM and NMSC. We decided to perform a study with the aim to evaluate the different survival in patients with MM-NMSC compared to control patients (MM-CTRL). PATIENTS AND METHODS: To evaluate prognosis in both groups, we analyzed disease-free survival (DFS) and overall survival (OS).Kaplan-Meier product was performed for the survival analysis. Median DFS was 73 months in group and 72 months in MM-CTRL patients (p = 0.4); while, median OS was 74.2 months in MM-NMSC patients and 63.1 in MM-CTRL (p < 0.001). Also at Odds-Ratio (OR), the statistical significance was maintained (p < 0.007) with a better prognostic value for MM-NMSC. RESULTS: Among group patients, the ones with a basal cell carcinoma showed a batter behavior, than the ones with squamous cell carcinoma (p = 0.01). CONCLUSIONS: Patients with MM-NMSC showed a better survival than MM-CTRL patients (p < 0.001). The causes of this improved survival are still unknown; probably the endogenous immune response can play a pivotal role in this class of patients. However, further studies are necessary to better understand this phenomenon, not yet explored in literature.

Elastofibroma dorsi: a histochemical and immunohistochemical study.

Elastofibroma dorsi (ED) is considered a member of a heterogeneous group of benign fibrous (fibroblastic or myofibroblastic) soft-tissue tumors, frequently localized in the periscapular region in middle aged or older individuals. However, the pathogenesis of ED is still unclear and many authors believe that ED results from a reactive hyperproliferation of fibroblastic tissue, while others suggest that it may be a consequence of a mechanical friction. In our study, we examined 11 cases of ED using histochemical and immunohistochemical methods, in order to extend the knowledge about extracellular matrix composition and histopathogenesis of ED. From the results it appeared that stroma and interspersed spindle cells of ED were positive for both periostin and tenascin-C. Mast cells tryptase-positive were also abundant throughout the lesion. The perivascular distribution of periostin and tenascin-C, associated with the CD34 positivity, suggest that endothelial-mesenchymal transition events can account for neovascularization and production of fibroelastic tissue characteristic of elastofibroma. Our data obtained in endothelial cells cultures demonstrated that elastin production is higher when the status of confluence of the cells is low. So, we can assume that such a phenomenon is a characteristic of mesenchymal/endothelial cells CD34 positive, in which elastin production results to be inversely proportional to the vascular differentiation of cellular elements. In the light of these considerations, we think that a cancerous nature of ED is unlikely. Overall, our study report, for the first time, a detailed description of extracellular matrix composition in ED, suggesting that a mechanical strain-dependent reactivation of periostin and tenascin-C expression, as well as of elastin deposition, could be responsible for development of ED.

Ink spot lentigo: singular clinical features in a case series of patients.

Ink spot lentigo, also known as reticulated black solar lentigo, is a melanotic macula commonly described in fair-skinned individuals on sun-exposed areas of the body. Clinically it is a darkly pigmented type of solar lentigo; herein the term ink spot lentigo. In contrast to common solar lentigines, ink spot lentigo is reported as a unique lesion. However usually ink spot lentigo appears among several common solar lentigines. We report a series of 5 patients who presented ink spot lentigo with typical dermoscopic pattern but singular clinical features.

Serum concentrations of IL-2, IL-6, IL-12 and TNF-α in patients with alopecia areata.

Alopecia areata (AA) has been represented as a restricted T cell-mediated autoimmune disease. Several studies have shown that cytokines may play an important role in its pathogenesis although many pathways exist. We investigated cytokine (IL-2, IL-6, IL-12, and TNFα) levels in peripheral blood mononuclear cell (PBMC) of 105 patients with different grade and duration of alopecia areata, to confirm that T-cell responses in AA is regulated via mechanisms of peripheral T-cell tolerance. We observed that IL-12 levels are higher for patients with bigger extensions and tend to increase according to the duration of the AA; TNFα instead, is more related to the gender of the patients and to the duration. Therefore abnormalities in cytokines production, showed by our results, may suggest that T-cell responses in AA scalp are closely regulated via mechanisms of peripheral T-cell tolerance and therefore confirm that this disease has an immuno-pathogenesis. Our aim is to shed light upon the complexity of AA underlying mechanisms and indicate pathways that may suggest future treatments.

Comparitive effectiveness of finasteride vs Serenoa repens in male androgenetic alopecia: a two-year study.

The objective of this open label study is to determine the effectiveness of Serenoa repens in treating male androgenetic alopecia (AGA), by comparing its results with finasteride. For this purpose, we enrolled 100 male patients with clinically diagnosed mild to moderate AGA. One group received Serenoa repens 320 mg every day for 24 months, while the other received finasteride 1 mg every day for the same period. In order to assess the efficacy of the treatments, a score index based on the comparison of the global photos taken at the beginning (T0) and at the end (T24) of the treatment, was used. The results showed that only 38% of patients treated with Serenoa repens had an increase in hair growth, while 68% of those treated with finasteride noted an improvement. Moreover finasteride was more effective for more than half of the patients (33 of 50, i.e. 66%), with level II and III alopecia. We can summarize our results by observing that Serenoa repens could lead to an improvement of androgenetic alopecia, while finasteride confirmed its efficacy. We also clinically observed, that finasteride acts in both the front area and the vertex, while Serenoa repens prevalently in the vertex. Obviously other studies will be necessary to clarify the mechanisms that cause the different responses of these two treatments.

Monilethrix treated with minoxidil.

In literature many different therapies are proposed to treat Monilethrix, but a definitive therapy still doe not exist. We decided to treat four patients affected by Monilethrix, with topical minoxidil 2%, 1 ml night and day for 1 year. Minoxidil led to a an increase of normal hair shaft without any side effects in all the patients. Therefore topical minoxidil 2% could be considered a good therapy to treat Monilethrix.

Action on the social determinants of health: a historical perspective.

A renewed concern with social factors has emerged in global public health, spearheaded by the World Health Organization's Commission on Social Determinants of Health. The coming decade may see significant health gains for disadvantaged populations if policies tackle the social roots of health inequities. To improve chances of success, global action on social determinants must draw lessons from history. This article reviews milestones in public health action on social determinants over the past 50 years. The goal is to bring into sharper focus the persistent challenges faced by social determinants agendas, along with distinctive opportunities now emerging. The historical record highlights the vulnerability of health policy approaches incorporating social determinants to resistance from entrenched interests. The Commission on Social Determinants of Health can consolidate political support by building collaborative relationships with policymakers in partner countries. However, this strategy must be complemented by engaging civil society constituencies. Historically, successful action on social determinants has been spurred by organized civil society demand.