Immunohistochemical analysis of the mechanistic target of rapamycin and hypoxia signalling pathways in basal cell carcinoma and trichoepithelioma

Background: Basal cell carcinoma (BCC) is the most common cancer in Caucasians. Trichoepithelioma (TE) is a benign neoplasm that strongly resembles BCC. Both are hair follicle (HF) tumours. HFs are hypoxic microenvironments, therefore we hypothesized that hypoxia-induced signalling pathways could be involved in BCC and TE as they are in other human malignancies. Hypoxia-inducible factor 1 (HIF1) and mechanistic/mammalian target of rapamycin (mTOR) are key players in these pathways. Objectives: To determine whether HIF1/mTOR signalling is involved in BCC and TE. Methods: We used immunohistochemical staining of formalin-fixed paraffin-embedded BCC (n = 45) and TE (n = 35) samples to assess activity of HIF1, mTORC1 and their most important target genes. The percentage positive tumour cells was assessed manually in a semi-quantitative manner and categorized (0%, 80%). Results: Among 45 BCC and 35 TE examined, expression levels were respectively 81% and 57% (BNIP3), 73% and 75% (CAIX), 79% and 86% (GLUT1), 50% and 19% (HIF1 alpha), 89% and 88% (pAKT), 55% and 61% (pS6), 15% and 25% (pMTOR), 44% and 63% (PHD2) and 44% and 49% (VEGF-A). CAIX, Glut1 and PHD2 expression levels were significantly higher in TE when only samples with at least 80% expression were included. Conclusions: HIF and mTORC1 signalling seems active in both BCC and TE. There are no appreciable differences between the two with respect to pathway activity. At this moment immunohistochemical analyses of HIF, mTORC1 and their target genes does not provide a reliable diagnostic tool for the discrimination of BCC and TE

the prevention of chronic diseases through ehealth a practical overview

Disease prevention is an umbrella term embracing individual-based or population-based interventions aimed at preventing the manifestation of diseases (primary prevention), reducing the impact of a disease that has arisen (secondary prevention), or mitigating the impact of an ongoing illness (tertiary prevention). Digital health has the potential to improve prevention of chronic diseases. Its application ranges from effective mHealth weight-loss intervention to prevent or delay the onset of diabetes in overweight adults to the cost-effective intervention on the provision of mental-health care via mobile-based or Internet-based programs to reduce the incidence or the severity of anxiety. The present contribution focuses on the effectiveness of eHealth preventive interventions and on the role of digital health in improving health promotion and disease prevention. We also give a practical overview on how eHealth interventions have been effectively implemented, developed, and delivered for the primary, secondary, and tertiary prevention of chronic diseases

Fractionated 5-aminolevulinic acid photodynamic therapy after partial debulking versus surgical excision for nodular basal cell carcinoma: A randomized controlled trial with at least 5-year follow-up

Background: Although effective in superficial basal cell carcinoma (BCC), the treatment effect of photodynamic therapy (PDT) in nodular BCC (nBCC) is still questionable. The relation between tumor thickness and PDT failure is unclear. Objective: We sought to compare long-term effectiveness of fractionated 20% 5-aminolevulinic acid (ALA)-PDT with prior partial debulking versus surgical excision in nBCC. The effect of tumor thickness on ALA-PDT failure was analyzed. Methods: 173 primary, histologically proven nBCCs in 151 patients were randomized to fractionated ALA-PDT (n = 85) or surgical excision (n = 88). Two PDT illuminations were performed with a 1-hour interval. Follow-up was at least 5 years posttreatment. Clinical recurrences were confirmed histologically. Results: A total of 171 nBCCs were treated and had a median follow-up of 67 months (range 0-106). At 60 months, 23 tumors had recurred in the ALA-PDT group and 2 tumors in the surgical excision group. Cumulative recurrence probabilities 5 years posttreatment were 30.7% (95% confidence interval [CI] 21.5%-42.6%) for ALA-PDT and 2.3% (95% CI 0.6%-8.8%) for surgical excision (P <.0001). Two tumors in the ALA-PDT group recurred at 72 and 91 months posttreatment. Cumulative probability of recurrence-free survival post-PDT was 65.0% (95% CI 51%-76%) for nBCC measuring greater than 0.7 mm in thickness and 94.4% (95% CI 67%-99%, P = .018) for tumors less than or equal to 0.7 mm. Limitations: Tumor thickness on punch biopsy specimen might differ from the total lesion thickness. Conclusions: In nBCC, 5-year cumulative probability of recurrence after surgical excision is lower than after fractionated ALA-PDT with prior debulking. Although surgical excision remains the gold standard of treatment, PDT might be an alternative for inoperable patients with thin

The effect of Mindfulness-Based Stress Reduction on wound healing: a preliminary study

Psychological factors have been shown to influence the process of wound healing. This study examined the effect of Mindfulness-Based Stress Reduction (MBSR) on the speed of wound healing. The local production of pro-inflammatory cytokines and growth factors was studied as potential underlying mechanism. Forty-nine adults were randomly allocated to a waiting-list control group (n = 26) or an 8-week MBSR group (n = 23). Pre- and post-intervention/waiting period assessment for both groups consisted of questionnaires. Standardized skin wounds were induced on the forearm using a suction blister method. Primary outcomes were skin permeability and reduction in wound size monitored once a day at day 3, 4, 5, 6, 7, and 10 after injury. Secondary outcomes were cytokines and growth factors and were measured in wound exudates obtained at 3, 6, and 22 h after wounding. Although there was no overall condition effect on skin permeability or wound size, post hoc analyses indicated that larger increases in mindfulness were related to greater reductions in skin permeability 3 and 4 days after wound induction. In addition, MBSR was associated with lower levels of interleukin (IL)-8 and placental growth factor in the wound fluid 22 h after wound induction. These outcomes suggest that increasing mindfulness by MBSR might have beneficial effects on early stages of wound healing. Trial Registration NTR3652, http://www.trialregister.nl

Cancer survivors' preference for follow-up care providers: A cross-sectional study from the population-based PROFILES-registry

Background: The best practice for the organization of follow-up care in oncology is under debate, due to growing numbers of cancer survivors. Understanding survivors' preferences for follow-up care is elementary for designing patient-centred care. Based on data from prostate cancer and melanoma survivors, this study aims to identify: 1) preferences for follow-up care providers, for instance the medical specialist, the oncology nurse or the general practitioner; 2) characteristics associated with these preferences and 3) the preferred care provider to discuss cancer-related problems. Material and methods: Survivors diagnosed with prostate cancer (N = 535) and melanoma (N = 232) between 2007 and 2013 as registered in The Netherlands Cancer Registry returned a questionnaire (response rate was 71% and 69%, respectively). A latent class cluster model analysis was used to define preferences and a multinomial logistic regression analysis was used to identify survivor-related characteristics associated with these preferences. Results: Of all survivors, 29% reported no preference, 40% reported a preference for the medical specialist, 20% reported a preference for both the medical specialist and the general practitioner and 11% reported a preference for both the medical specialist and the oncology nurse. Survivors who were older, lower/intermediate educated and women were more likely to have a preference for the medical specialist. Lower educated survivors were less likely to have a preference for both the medical specialist and the general practitioner. Overall, survivors prefer to discuss diet, physical fitness and fatigue with the general practitioner, and hereditary and recurrence with the medical specialist. Only a small minority favored to discuss cancer-related problems with the oncology nurse. Conclusions: Survivors reported different preferences for follow-up care providers based on age, education level, gender and satisfaction with the general practitioner, showing a need for tailored follow-up care in oncology. The results indicate an urgency to educate patients about transitions in follow-up care