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Background/aim: Hydrochlorothiazide (HCTZ) possesses well-described photosensitizing properties, and a causal association with nonmelanoma skin cancer (NMSC) was recently shown. However, previous studies have not shown whether HCTZ use is associated with the risk of recurrence of basal cell carcinoma (BCC) or squamous cell carcinoma (SCC). This study aims to investigate the association between HCTZ use and recurrence in patients with NMSC.Materials and methods: We identified cases with NMSC from our hospital archives during the period between 2013 and 2019. Patients were divided into groups according to the pathological diagnosis, HCTZ use, and recurrence. Multivariable analysis was performed to determine factors associated with recurrence in BCC and SCC.Results: Recurrences of BCC were significantly higher in HCTZ users with ORs of 4.839221 (95% confidence interval [CI], 1.22-19.12). In HCTZ users, NMSC cases were associated with increased age (p 0.001 for both BCC and SCC). BCC recurrences were statistically significant with age, longer follow-up, and positive margins after excision in HCTZ users (p = 0.048, 0.020, and, 0.003, respectively). SCC recurrences were not significantly associated with HCTZ use. Conclusion: HCTZ use is significantly associated with BCC recurrences. Especially in the elderly population, cases with a positive margin should be followed closely.

Background/aim: Hydrochlorothiazide (HCTZ) possesses well-described photosensitizing properties, and a causal association with nonmelanoma skin cancer (NMSC) was recently shown. However, previous studies have not shown whether HCTZ use is associated with the risk of recurrence of basal cell carcinoma (BCC) or squamous cell carcinoma (SCC). This study aims to investigate the association between HCTZ use and recurrence in patients with NMSC.Materials and methods: We identified cases with NMSC from our hospital archives during the period between 2013 and 2019. Patients were divided into groups according to the pathological diagnosis, HCTZ use, and recurrence. Multivariable analysis was performed to determine factors associated with recurrence in BCC and SCC.Results: Recurrences of BCC were significantly higher in HCTZ users with ORs of 4.839221 (95% confidence interval [CI], 1.22-19.12). In HCTZ users, NMSC cases were associated with increased age (p 0.001 for both BCC and SCC). BCC recurrences were statistically significant with age, longer follow-up, and positive margins after excision in HCTZ users (p = 0.048, 0.020, and, 0.003, respectively). SCC recurrences were not significantly associated with HCTZ use. Conclusion: HCTZ use is significantly associated with BCC recurrences. Especially in the elderly population, cases with a positive margin should be followed closely.

The high incidence of sunlight-induced human skin cancers reveals a need for more effective photosensitizing agents. In this study, we compared the efficacy of prophylactic photodynamic therapy (PDT) when methylene blue (MB), riboflavin (RF), or methyl aminolevulinate (MAL) were used as photosensitizers. All mice in four groups of female C3.Cg/TifBomTac hairless immunocompetent mice (N = 100) were irradiated with three standard erythema doses of solar-simulated ultraviolet radiation (UVR) thrice weekly. Three groups received 2 x 2 prophylactic PDT treatments (days 45 + 52 and 90 + 97). The PDT treatments consisted of topical administration of 16% MAL, 20% MB, or 20% RF, and subsequent illumination that matched the photosensitizers' absorption spectra. Control mice received no PDT. We recorded when the first, second, and third skin tumors developed. The pattern of tumor development after MB-PDT or RF-PDT was similar to that observed in irradiated control mice (p > 0.05). However, the median times until the first, second, and third skin tumors developed in mice given MAL-PDT were significantly delayed, compared with control mice (256, 265, and 272 vs. 215, 222, and 230 days, respectively; p < 0.001). Only MAL-PDT was an effective prophylactic treatment against UVR-induced skin tumors in hairless mice.

The high incidence of sunlight-induced human skin cancers reveals a need for more effective photosensitizing agents. In this study, we compared the efficacy of prophylactic photodynamic therapy (PDT) when methylene blue (MB), riboflavin (RF), or methyl aminolevulinate (MAL) were used as photosensitizers. All mice in four groups of female C3.Cg/TifBomTac hairless immunocompetent mice (N = 100) were irradiated with three standard erythema doses of solar-simulated ultraviolet radiation (UVR) thrice weekly. Three groups received 2 x 2 prophylactic PDT treatments (days 45 + 52 and 90 + 97). The PDT treatments consisted of topical administration of 16% MAL, 20% MB, or 20% RF, and subsequent illumination that matched the photosensitizers' absorption spectra. Control mice received no PDT. We recorded when the first, second, and third skin tumors developed. The pattern of tumor development after MB-PDT or RF-PDT was similar to that observed in irradiated control mice (p > 0.05). However, the median times until the first, second, and third skin tumors developed in mice given MAL-PDT were significantly delayed, compared with control mice (256, 265, and 272 vs. 215, 222, and 230 days, respectively; p < 0.001). Only MAL-PDT was an effective prophylactic treatment against UVR-induced skin tumors in hairless mice.

Basal-cell carcinoma is the most common form of skin cancer and usually easiest to treat. The hedgehog-signaling pathway plays an important role in the development of basal cell carcinoma. This dissertation is about systemic treatment of the very rare, advanced or metastatic basal cell carcinoma with the hedgehog inhibitor vismodegib. In addition, this thesis delves into research on basal-cell naevus syndrome, a congenital disorder, in which large amounts of basal-cell carcinomas arise at a young age. This syndrome is usually caused by a mutation in the PTCH1 gene, which plays a role in the hedgehog-signaling pathway. The thesis shows that this mutation can also be present in only a select part of the body's cells, so-called genetic mosaicism.

Background In order to evaluate and improve aesthetic outcome for patients undergoing dermatological surgery, a reliable evaluation tool must be used. The 4-point scale and the Patient and Observer Scar Assessment Scale (POSAS) were both developed for this purpose.Objective To compare the reliability of the POSAS scale with the 4-point scale for facial linear surgical scars and to assess the influence of different scar characteristics on the overall impression.Methods Patients visiting the outpatient clinics of the Maastricht University Medical Centre with linear facial scars were included. The 4-point scale and the Observer Scar Assessment Scale (OSAS) were completed by three independent observers. The Patient Scar Assessment Scale (PSAS) was completed by the patient on the day of the visit and 2 weeks later. The intra-class correlation coefficient (ICC) with corresponding 95% confidence intervals (CI) were calculated to assess the reliability of the scales. Linear multivariate regression analyses were performed to evaluate how the score on each aspect affected the overall opinion.Results Fifty scars in 50 patients were included. The ICC of the 4-point scale was 0.819 (95% CI: 0.708-0.892) for multiple observers and 0.602 (95% CI: 0.447-0.734) for single observer. These were superior to the ICCs of total OSAS scores (0.783 95% CI: 0.547-0.888 for multiple observers and 0.546 95% CI: 0.287-0.726 for single observer). ICCs of individual sub-items on the OSAS scored even lower. The sub-items contributed differently to the overall opinion among the different observers or patient.Conclusion In terms of reliability, the overall opinion and the 4-point scale were superior to the total POSAS score or the sub-items. Observers do not weight individual scar characteristics equally to arrive at an overall opinion, which challenges the assumption that calculating a total POSAS score by summing of the scores on the individual items is a valid appro

Background In order to evaluate and improve aesthetic outcome for patients undergoing dermatological surgery, a reliable evaluation tool must be used. The 4-point scale and the Patient and Observer Scar Assessment Scale (POSAS) were both developed for this purpose.Objective To compare the reliability of the POSAS scale with the 4-point scale for facial linear surgical scars and to assess the influence of different scar characteristics on the overall impression.Methods Patients visiting the outpatient clinics of the Maastricht University Medical Centre with linear facial scars were included. The 4-point scale and the Observer Scar Assessment Scale (OSAS) were completed by three independent observers. The Patient Scar Assessment Scale (PSAS) was completed by the patient on the day of the visit and 2 weeks later. The intra-class correlation coefficient (ICC) with corresponding 95% confidence intervals (CI) were calculated to assess the reliability of the scales. Linear multivariate regression analyses were performed to evaluate how the score on each aspect affected the overall opinion.Results Fifty scars in 50 patients were included. The ICC of the 4-point scale was 0.819 (95% CI: 0.708-0.892) for multiple observers and 0.602 (95% CI: 0.447-0.734) for single observer. These were superior to the ICCs of total OSAS scores (0.783 95% CI: 0.547-0.888 for multiple observers and 0.546 95% CI: 0.287-0.726 for single observer). ICCs of individual sub-items on the OSAS scored even lower. The sub-items contributed differently to the overall opinion among the different observers or patient.Conclusion In terms of reliability, the overall opinion and the 4-point scale were superior to the total POSAS score or the sub-items. Observers do not weight individual scar characteristics equally to arrive at an overall opinion, which challenges the assumption that calculating a total POSAS score by summing of the scores on the individual items is a valid appro

At the end of the 19th century, researchers observed that biological substances have frequency-dependent electrical properties and that tissue behaves like a capacitor [1]. Consequently, in the first half of the 20th century, the permittivity of many types of cell suspensions and tissues was characterized up to frequencies of approximately 100 MHz. From the measurements, conclusions were drawn, in particular, about the electrical properties of the cell membranes, which are the main contributors to the tissue impedance at frequencies below 10 MHz [2]. In 1926, a study found a significant different permittivity for breast cancer tissue compared with healthy tissue at 20 kHz [3]. After World War II, new instrumentation enabled measurements up to 10 GHz, and a vast amount of data on the dielectric properties of different tissue types in the microwave range was published [4]-[6]., QC 20150512

This paper reports for the first time on the 2-dimensional scanning performance of a micromachined millimeter-wave (100 GHz) near-field probe with a substantially reduced tip size which is designed for skin cancer diagnosis. Furthermore, it introduces a novel concept of creating inhomogeneous test samples with tailor-made and locally altered permittivity which mimick skin tissue with small anomalies and are used for characterizing the probe. A probe prototype with a tip size of 300 x 600 mu m(2) and test samples with permittivity in the range of cancerous and healthy skin tissue were fabricated by micromachining and used for evaluating the sensitivity and resolution of the probe. This paper reports for the first time on 2-dimensional scanning performance, resolution, repeatability, long-term stability, and sensitivity, which are important for qualifying such measurement probes for medical applications. The resolution of the prototype, which is important for early detection of small tumor speckles, was found to be better than 200 mu m, i.e. 1/6 of the medium-normalized wavelength. The reproducibility of the probe setup including operator uncertainty is 1.36% (1 sigma) and the long term stability of reference measurements is 0.59% (1 sigma) over 8 hours., QC 20130815

Vitamin D may have anti-skin cancer effects, but population-based evidence is lacking. We therefore assessed associations between vitamin D status and skin cancer risk in an Australian subtropical community. We analyzed prospective skin cancer incidence for 11 years following baseline assessment of serum 25(OH)-vitamin D in 1,191 adults (average age 54 years) and used multivariable logistic regression analysis to adjust risk estimates for age, sex, detailed assessments of usual time spent outdoors, phenotypic characteristics, and other possible confounders. Participants with serum 25(OH)-vitamin D concentrations above 75 nmol l(-1) versus those below 75 nmol l(-1) more often developed basal cell carcinoma (odds ratio (OR)=1.51 (95% confidence interval (CI): 1.10-2.07, P=0.01) and melanoma (OR=2.71 (95% CI: 0.98-7.48, P=0.05)). Squamous cell carcinoma incidence tended to be lower in persons with serum 25(OH)-vitamin D concentrations above 75 nmol l(-1) compared with those below 75 nmol l(-1) (OR=0.67 (95% CI: 0.44-1.03, P=0.07)). Vitamin D status was not associated with skin cancer incidence when participants were classified as above or below 50 nmol l(-1) 25(OH)-vitamin D. Our findings do not indicate that the carcinogenicity of high sun exposure can be counteracted by high vitamin D status. High sun exposure is to be avoided as a means to achieve high vitamin D status.

Here we demonstrate that intermittently sun-exposed human skin contains an extensive number of phenotypically intact cell compartments bearing missense and nonsense mutations in the p53 tumor suppressor gene. Deep sequencing of sun-exposed and shielded microdissected skin from mid-life individuals revealed that persistent p53 mutations had accumulated in 14% of all epidermal cells, with no apparent signs of a growth advantage of the affected cell compartments. Furthermore, 6% of the mutated epidermal cells encoded a truncated protein. The abundance of these events, not taking into account intron mutations and mutations in other genes that also may have functional implications, suggests an extensive tolerance of human cells to severe genetic alterations caused by UV light, with an estimated annual rate of accumulation of similar to 35,000 new persistent protein-altering p53 mutations in sun-exposed skin of a human individual., QC 20110214

Background: The hedgehog signaling pathway is vital in early development, but then becomes dormant, except in some cancer tumours. Hedgehog inhibitors are being developed for potential use in cancer. Objectives/Methods: The objective of this evaluation is to review the initial clinical studies of the hedgehog inhibitor, GDC-0449, in subjects with cancer. Results: Phase I trials have shown that GDC-0449 has benefits in subjects with metastatic or locally advanced basal-cell carcinoma and in one subjects with medulloblastoma. GDC-0449 was well tolerated. Conclusions: Long term efficacy and safety studies of GDC-0449 in these conditions and other solid cancers are now underway. These clinical trials with GDC-0449, and trials with other hedgehog inhibitors, will reveal whether it is beneficial and safe to inhibit the hedgehog pathway, in a wide range of solid tumours or not.

Background/purpose: Bio-electrical impedance spectra of skin cancer and other lesions can be assessed using both regular non-invasive probes and a novel type of microinvasive electrode system with a surface furnished with tiny spikes that penetrate stratum corneum. The aim of the study was to compare the accuracy of detection for various types of skin cancer using impedance spectra measured with these two different electrode systems in an objective way without optimising the power of discrimination. Methods: Impedance spectra of 99 benign nevi, 28 basal cell carcinomas (BCC), and 13 malignant melanomas (MM) were measured using the two electrode systems. Classification of the lesions was made using Fisher's linear discriminant, and the sensitivities and specificities of the techniques were estimated using cross-validation. Results: The best separation between nevi and BCC was achieved using the regular non-invasive probe (96% sensitivity and 86% specificity), whereas the best separation between nevi and MM was achieved using the microinvasive electrodes (92% sensitivity and 80% specificity). Conclusions: Our results indicate that the choice of electrode system is application dependent., QC 20100525

Electrical bio-impedance can be used to assess skin cancers and other cutaneous lesions. The aim of this study was to distinguish skin cancer from benign nevi using multifrequency impedance spectra. Electrical impedance spectra of about 100 skin cancers and 511 benign nevi were measured. Impedance of reference skin was measured ipsi-laterally to the lesions. The impedance relation between lesion and reference skin was used to distinguish the cancers from the nevi. It was found that it is possible to separate malignant melanoma from benign nevi with 75% specificity at 100% sensitivity, and to distinguish nonmelanoma skin cancer from benign nevi with 87% specificity at 100% sensitivity. The power of skin cancer detection using electrical impedance is as good as, or better than, conventional visual screening made by general practitioners., QC 20100525