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Objective Nonmelanoma skin cancer (NMSC) is one of the most diagnosed cancers in the world, with the number of new occurrences rising every year. Most patients with facial skin cancer experience cancer-related worry. Yet, little is known about their worry during the period after cancer treatment. This study aimed to assess the long-term change of cancer worry after surgical treatment in patients with NMSC. Methods Patients undergoing surgery for facial NMSC between December 2017 and March 2020 were asked to complete the FACE-Q Skin Cancer-Cancer Worry scale before (baseline), 3-month, and 1-year post-surgery. Results A total of 151 patients completed the baseline and 3-month, and 99 (65.6%) the 1-year post-operative survey. A significant decrease in cancer worry score was seen between baseline and 3-month post-surgery (p < 0.001). No difference was found between the 3-month and 1-year post-surgery scores (p = 0.78). Less improvement in cancer worry was seen for patients who had one facial skin cancer in their medical history (p = 0.001) and patients who had a history of facial surgery (p < 0.001). Conclusion Post-surgery patients still experience cancer worry. Therefore, targeted counseling might be of value when coping with cancer-related concerns. Patients with a history of facial NMSC and patients with a history of facial surgery might benefit from additional counseling.

Background: The histological subtype of basal-cell carcinoma (BCC) is often based on a punch biopsy; only a small part is evaluated, possibly leading to misclassification. Consensus on the optimal approach to process punch biopsies is lacking, though accurate subtyping is important for appropriate treatment. Objective: The aim is to investigate whether evaluating 4 levels of a punch biopsy instead of 1 or 2 levels leads to more accurate subtyping of BCC. Methods: In a retrospective study we evaluated 87 punch biopsies of histologically confirmed BCCs. The primary outcome was the proportion of “more aggressive” BCCs (nonsuperficial vs. superficial, infiltrative vs. nodular subtype) that was missed by evaluation on 1 or 2 levels, using 4-level diagnosis as reference standard. Results: Eighty-five cases were available for analysis. Subtyping based on 1 level resulted in discrepancies with 4-level diagnosis in 16.5% of all cases. Underdiagnosis occurred in 14 of 58 nonsuperficial BCCs (24.1%, 95% CI: 13.9–37.2). Seven of 38 nodular BCCs (18.4%, 95% CI: 7.74–34.3) were diagnosed as superficial in 1 level, and 7 of 20 infiltrative BCCs (35%, 95% CI: 15.4–59.2) were diagnosed as superficial (n = 2) or nodular (n = 5) in 1 level. Conclusion: In order to maximize correct subtyping and plan appropriate treatment, we advise to evaluate at least 2, but preferably more, levels of a punch biopsy to determine the BCC subtype.

Background: Little is known about the impact of keratinocyte cancer (KC) and its treatment on health-related quality of life (HRQoL). Objectives: The objectives of the present study were (1) to evaluate HRQoL among patients with KC in a population-based setting and compare this with an age- end sex-matched normative population and (2) to compare HRQoL, satisfaction with care, and cosmetic results among patients who underwent conventional excision, Mohs’ micrographic surgery, or radiotherapy. Method: A random sample of 347 patients diagnosed with cutaneous basal cell or squamous cell carcinoma in the head and neck area between January 1, 2010, and December 31, 2014, were selected from the Netherlands Cancer Registry (NCR) and were invited to complete a questionnaire on HRQoL, satisfaction with care, and cosmetic results. Data were collected within Patient-Reported Outcomes Following Initial Treatment and Long-term Evaluation of Survivorship (PROFILES). Outcomes were compared to an age- and sex-matched normative population. Results: Two hundred fifteen patients with KC returned a completed questionnaire (62% response). Patients with KC reported better global quality of life (79.6 vs. 73.3, p < 0.01) and less pain (p < 0.01) compared to the normative population. No statistically significant differences in HRQoL, satisfaction with care, and cosmetic results were found between patients with KC who underwent conventional excision, Mohs’ micrographic surgery, or radiotherapy. Conclusions: The impact of KC and its treatment seems relatively low and more positive than negative as patients reported better HRQoL compared to an age- and sex-matched normative population, probably due to adaptation. No statistically significant differences between treatment types were found concerning HRQoL, patient satisfaction, and cosmetic results. This information could be used by healthcare professionals involved in KC care to improve patients’ knowledge about different aspects of the disease as patient’s preference is an important factor for treatment choice.

Polypoid basal-cell carcinoma (BCC) is a rare tumor, considered a clinical and histopathological variant of the nodular BCC, presenting broad exophytic or pedunculated base that connects to the surface of the skin and histopathologically displays the neoplastic aggregations restricted to the polypoid zone. We report a clinical case of BCC, with a bibliographical review, highlighting the clinical similarity of such malignant tumor with other benign and malignant tumors of the skin, besides the importance of dermoscopy for the diagnostic aid.

Objective: In this study, we aimed to evaluate residual tumors and recurrence rates of malignant melanoma (MM) and a non-melanoma skin cancer of (NMSC) head and neck region. Patients and Methods: Medical data of a total of 398 lesions of 323 patients who underwent surgical excision for a basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and malignant melanoma (MM) were retrospectively analyzed. All patients were classified according to age, sex, location of the tumor, histopathological diagnosis, lesion diameter, excision diameter, surgical margin status, and residual lesions and recurrence rates. Results: There were 244 lesions (61.3%) in 189 males and 154 lesions (38.7%) in 134 females. The most common type of skin cancer was BCC in 268 lesions (67%), followed by SCC in 122 (31%), and MM in eight (2%), respectively. Recurrence was seen in 3% of the NMSC cases and in 25% of the MM cases. There was a statistically significant correlation between the histopathological diagnosis and recurrence rates. Compared to NMSC, MM cases had a higher risk for recurrence (p=0.029). Conclusion: Our study results suggest that recurrence is associated with the localization and type of the tumor, but not with the age or sex of the patient.

Background Information about global and local epidemiology and trends of skin cancers is limited, which increases the difficulty of cutaneous cancer control. Methods To estimate the global spatial patterns and temporal trends of skin cancer burden. Based on the GBD 2019, we collected and analyzed numbers and age‐standardized rates (ASR) of skin cancer incidence, disability‐adjusted life years (DALYs) and mortality (ASIR, ASDR, and ASMR) in 204 countries from 1990 through 2019 were estimated by age, sex, subtype (malignant skin melanoma [MSM], squamous‐cell carcinoma [SCC], and basal‐cell carcinoma [BCC]), Socio‐demographic Index (SDI), region, and country. Temporal trends in ASR were also analyzed using estimated annual percentage change. Results Globally, in 2019, there were 4.0 million BCC, 2.4 million SCC, and 0.3 million MSM. There were approximately 62.8 thousand deaths and 1.7 million DALYs due to MSM, and 56.1 thousand deaths and 1.2 million DALYs were attributed to SCC, respectively. The men had higher ASR of skin cancer burden than women. The age‐specific rates of global skin cancer burden were higher in the older adults, increasing trends observed from 55 years old. Geographically, the numbers and ASR of skin cancers varied greatly across countries, with the largest burden of ASIR in high SDI regions. However, an unexpected increase was observed in some regions from 1990 to 2019, such as East Asia, and Sub‐Saharan Africa. Although there was a slight decrease of the ASMR and ASDR, the global ASIR of MSM dramatically increased, 1990–2019. Also, there was a remarkable increase in ASR of BCC and SCC burden. Conclusions Skin cancer remains a major global public health threat. Reducing morbidity and mortality strategies such as primary and secondary prevention should be reconsidered, especially in the most prevalent and unexpected increased regions, especially for those areas with the greatest proportions of their population over age 55., Main results of this systematic analysis showed that globally, in addition to a slight fall in mortality of melanoma, there was a dramatic increase in skin cancers burden from 1990 to 2019. Geographically, an unexpected increase was observed in some territories, 1990–2019, such as East Asia and Sub‐Saharan Africa, which were usually considered as low incidence areas in the past. Globally, increased efforts are needed in skin cancer prevention, especially, in regions with a high and/or increased burden of cutaneous cancer.

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 × 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 &gt, 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 &lt, 0.001). Only MAL-PDT was an effective prophylactic treatment against UVR-induced skin tumors in hairless mice.

Background Skin cancer is the most commonly occurring type of cancer. However, the influence of facial skin cancer surgery on patients’ perceived aesthetic appearance is poorly understood. The objective of this study was to provide an insight into how patients perceive the aesthetic outcome of facial skin cancer surgery by means of a specialised patient-reported outcome measure designed for the aesthetic evaluation of the face: the FACE-Q. Methods A total of 47 patients with non-melanoma skin cancer who were scheduled for Mohs’s micrographic surgery (MMS) or standard surgical excision (SE) were included. These patients filled out three different FACE-Q questionnaires: satisfaction with facial appearance, social function, and satisfaction with outcome. Follow-up was conducted after baseline at 1 month and 3 months post-surgery. Results No significant differences were detected between baseline and follow-up regarding social function and satisfaction with facial appearance. However, after 3 months, patients were significantly more satisfied with the result of surgery when compared with the 1-month post-surgery follow-up. Conclusions The perceived aesthetic appreciation of patients does not seem to be significantly influenced by facial skin cancer SE or MMS surgery in this 3-month follow-up study. Level of evidence: Not ratable.

Background Skin cancer is common after radiotherapy among childhood cancer survivors (CCSs). We studied risks and risk factors for subsequent skin cancers, with emphasis on radiation dose, exposed skin surface area, and chemotherapeutic agents. Methods The DCOG-LATER cohort study includes 5-year Dutch CCSs diagnosed 1963–2001. Subsequent skin cancers were identified from record linkages with the Netherlands Cancer Registry and Dutch Pathology Registry. Incidence rates were compared with general population rates. Multivariable Cox regression models were used, applying a novel method of case-control sampling enabling use of tumor location in cohort analyses. All statistical tests were two-sided. Results Among 5843 CCSs, 259 developed 1061 basal cell carcinomas (BCCs) (standardized incidence ratio [SIR] = 29.8, 95% confidence interval [CI] = 26.3 to 33.6; excess absolute risk per 10 000 person-years (EAR) = 24.6), 20 had melanoma (SIR = 2.3, 95% CI = 1.4 to 3.5; EAR = 1.1), and 10 had squamous cell carcinoma (SIR = 7.5, 95% CI = 3.6 to 13.8; EAR = 0.8). Cumulative incidence of BCC 40 years after childhood cancer was 19.1% (95% CI = 16.6 to 21.8%) after radiotherapy vs 0.6% expected based on general population rates. After a first BCC, 46.7% had more BCCs later. BCC risk was associated with any radiotherapy to the skin compartment of interest (hazard ratio [HR] = 14.32, 95% CI = 10.10 to 20.29) and with estimated percentage in-field skin surface area (26–75%: HR = 1.99, 95% CI = 1.24 to 3.20; 76–100%: HR = 2.16, 95% CI = 1.33 to 3.53, vs 1–25% exposed; Ptrend among exposed = .002), but not with prescribed radiation dose and likelihood of sun-exposed skin-area. Of all chemotherapy groups examined, only vinca alkaloids increased BCC risk (HR = 1.54, 95% CI = 1.04 to 2.27). Conclusion CCSs have a strongly, 30-fold increased BCC risk. BCC risk appears to increase with increasing skin surface area exposed. This knowledge underscores the need for awareness by survivors and their health care providers.

Treatment of choice for nodular basal-cell carcinomas (BCCs) is complete excision, implying that small lesions are of minor concern. Metastasis is very rare (

International audience; In this article, we propose a segmentation algorithm for skin lesions in 3D high-frequency ultrasound images. The segmentation is done on melanoma and Basal-cell carcinoma tumors, the most common skin cancer types, and could be used for diagnosis and surgical excision planning in a clinical context. Compared with previously proposed algorithms, which tend to underestimate the size of the lesion, we propose two new boundary terms which provide significant improvements of the accuracy. The first is a probabilistic boundary expansion (PBE) term designed to broaden the segmented area at the boundaries, which uses the feature asymmetry criterion. The second is a curvature dependent regularization (CDR), which aims at overcoming the tendency of standard regularization to shrink segmented areas. On a clinical dataset of 12 patients annotated by a dermatologist, the proposed algorithm has a comparable Dice index but increases the sensitivity by . The proposed algorithm improves the sensitivity for all lesions, and the obtained sensitivity is close to that of the intra-observer variability.

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 approach.

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.

Basal cell carcinoma is one of the most common malignancies. Despite a wide range of treatment options and relatively good prognosis of the disease, there may be restrictions on the use of standard methods of treatment because of elderly patients, their physical condition and characteristics of the tumor localization. We provide clinical examples of successful treatment of basal cell carcinoma of the head and neck with Kuraderm BEC5. This is a drug with anti-tumor activity for topical use made on the basis of glycoalkaloids of plants of nightshade family.

Background The role of general practitioners (GPs) in skin cancer care is increasing. Previous, hospital-based studies suggest that GPs might not have the capabilities to gain responsibility concerning skin cancer care. Objectives To evaluate the current approach of GPs towards skin lesions suspected of malignancy in the Netherlands. Methods In three general practices, all consultations in 2015 concerning skin lesions suspected of malignancy were identified and reviewed. Patients demographics, circumstances of consultation, evaluation of skin lesion(s), presumed diagnosis, diagnostic accuracy and policy were evaluated. Results Five hundred and eighty consultations were identified. Patient took initiative for encounter in 90%. Case-finding occurred in 2%. Diagnostic tools were used in 22%; dermoscopy was used in 8% and a diagnostic excision in 10%. The GP diagnosed a benign lesion in 69%. Therapeutic interventions were applied in 31% and a wait-and-see policy in 40%. The diagnosis after referral was a benign tumour in 39% of the cases, a malignancy in 29% and a premalignant lesion in 17%. The positive predictive value (PPV) of the presumed benign, malignant and premalignant diagnoses was 86%, 54% and 18%, respectively. Conclusions Most lesions that are presented to the GP with a suspicion of a malignancy appear to be benign lesions. In the examined practices, the diagnosis of the GP is mainly based on clinical examination and little use is made of available diagnostic tools. The use of a diagnostic tool like a biopsy might prevent unnecessary referrals.

BackgroundBasal cell nevus syndrome (BCNS) is an autosomal dominant disorder characterized by multiple basal cell carcinomas (BCCs), maxillary keratocysts, and cerebral calcifications. BCNS most commonly is caused by a germline mutation in the patched-1 (PTCH1) gene. PTCH1 mutations are also described in patients with holoprosencephaly.MethodsWe have established a locus-specific database for the PTCH1 gene using the Leiden Open Variation Database (LOVD). We included 117 new PTCH1 variations, in addition to 331 previously published unique PTCH1 mutations. These new mutations were found in 141 patients who had a positive PTCH1 mutation analysis in either the VU University Medical Centre (VUMC) or Maastricht University Medical Centre (MUMC) between 1995 and 2015.ResultsThe database contains 331 previously published unique PTCH1 mutations and 117 new PTCH1 variations.ConclusionWe have established a locus-specific database for the PTCH1 gene using the Leiden Open Variation Database (LOVD). The database provides an open collection for both clinicians and researchers and is accessible online at http://www.lovd.nl/PTCH1..

Background While skin cancer incidence is rising throughout Europe, general practitioners (GP) feel unsure about their ability to diagnose skin malignancies. Objectives To evaluate whether the GP has sufficient validated clinical decision aids and tools for the examination of potentially malignant skin lesions. Methods We conducted a review searching Medline and the Cochrane Library. In addition, reference lists and personal archives were examined. Outcome measures were sensitivity and specificity but also the advantages and disadvantages of different clinical decision aids and tools. Results No clinical decision aids or tools for the examination of non-pigmented lesions are available. Clinical decision aids and tools for the examination of pigmented lesions have mostly been studied in secondary care and, in primary care, randomised clinical trials comparing the additional value of a clinical decision aid or tools to care are scarce. Conclusion Sufficiently validated clinical decision aids and tools for the examination of potentially malignant skin lesions are lacking in general practice. The clinical decision aids and tools available in primary care need to be studied.

Basal-cell carcinoma is a commonly occurring skin malignancy that has the potential to progress into locally invasive or resistant disease, as well as spread distantly. Due to advances in the molecular understanding of the disease over the last two decades, it has been discovered that the Hedgehog pathway plays an important role in the pathogenesis of this disease and can be exploited as a treatment target. Several agents that inhibit the Hedgehog pathway have reached clinical studies and one drug, vismodegib, has recently been US Food and Drug Administration (FDA) approved based on clinical activity and tolerability in patients with advanced basal-cell carcinoma. This review will describe the clinical development of vismodegib, as well as the proper application of the drug in clinical practice. Other important clinical questions, such as mechanisms of resistance to vismodegib and the role of other Hedgehog pathway inhibitors currently in development will also be discussed.

Background: Benign lichenoid keratosis (BLK, LPLK) is often misdiagnosed clinically as superficial basal-cell carcinoma (BCC), especially when occurring on the trunk. However, BCCs undergoing regression may be associated with a lichenoid interface dermatitis that may be misinterpreted as BLK in histopathologic sections. Methods: In order to assess the frequency of remnants of BCC in lesions interpreted as BLK, we performed step sections on 100 lesions from the trunk of male patients that had been diagnosed as BLK. Results: Deeper sections revealed remnants of superficial BCC in five and remnants of a melanocytic nevus in two specimens. In the original sections of cases in which a BCC showed up, crusts tended to be more common, whereas vacuolar changes at the dermo-epidermal junction and melanophages in the papillary dermis tended to be less common and less pronounced. Conclusions: Lesions from the trunk submitted as BCC and presenting histopathologically as a lichenoid interface dermatitis are not always BLKs. Although no confident recommendations can be given on the basis of this limited study, deeper sections may be warranted if lesions are crusted and/or associated with only minimal vacuolar changes at the dermo-epidermal junction and no or few melanophages in the papillary dermis.

Basal-cell carcinoma (BCC) rarely occurs on the lip. We herein report a case of an 89-year-old male, who presented with a blackish nodule on the vermilion border and the outer mucosa of the right side of the upper lip. A diagnosis of pigmented BCC was made by histopathological examination. The patient was successfully treated by Abbe flap with excellent esthetic and functional results. We have reviewed 64 cases of lip BCCs previously reported. There was no gender predominance, and the upper lip was involved 1.5 times higher than the lower lip. There was no lymph node metastasis, and thus, lip BCC had a good prognosis.

Contains fulltext : 81560.pdf (Publisher’s version ) (Closed access) The common sequence variants that have recently been associated with cancer risk are particular to a single cancer type or at most two. Following up on our genome-wide scan of basal cell carcinoma, we found that rs401681[C] on chromosome 5p15.33 satisfied our threshold for genome-wide significance (OR = 1.25, P = 3.7 x 10(-12)). We tested rs401681 for association with 16 additional cancer types in over 30,000 cancer cases and 45,000 controls and found association with lung cancer (OR = 1.15, P = 7.2 x 10(-8)) and urinary bladder, prostate and cervix cancer (ORs = 1.07-1.31, all P < 4 x 10(-4)). However, rs401681[C] seems to confer protection against cutaneous melanoma (OR = 0.88, P = 8.0 x 10(-4)). Notably, most of these cancer types have a strong environmental component to their risk. Investigation of the region led us to rs2736098[A], which showed stronger association with some cancer types. However, neither variant could fully account for the association of the other. rs2736098 corresponds to A305A in the telomerase reverse transcriptase (TERT) protein and rs401681 is in an intron of the CLPTM1L gene.

The aim of this study was to compare the expressions of mRNA for metalloproteinases (MMP-2 and MMP-9) and type IV collagen in two different histological types of basal-cell carcinoma (BCCs; nodular and infiltrative) and in normal tissues from the tumor interface. The study included biopsy specimens of the skin involved with BCC and normal skin adjacent the lesion. The expressions of mRNA for MMP-2, MMP-9 and type IV collagen were determined by means of RT-PCR (Reverse transcription polymerase chain reaction). The level of type IV collagen mRNA in nodular and infiltrative BCCs turned out to be significantly lower, and the expressions of MMP-2 and MMP-9 mRNA significantly higher than in normal tissues adjacent to these tumors. The expression of mRNA for MMP-9 but not for MMP-2 was significantly higher in infiltrative BCCs than in the nodular BCCs. In turn, normal tissues adjacent to nodular BCCs showed significantly higher levels of mRNA for MMP-2 and significantly lower levels of type IV collagen mRNA than the normal tissues from the interface of infiltrative BCCs. The findings suggest that MMP-2 and MMP-9 could be used as prognostic factors of BCCs.

The progression of tumours to malignancy is commonly considered to arise through lineal evolution, a process in which mutations conferring pro-oncogenic cellular phenotypes are acquired by a succession of ever-more dominant clones. However, this model is at odds with the persistent polyclonality observed in many cancers. We propose that an alternative mechanism for tumour progression, called interclonal cooperativity, is likely to play a role at stages of tumour progression when mutations cause microenvironmental changes, such as occur with epithelial-mesenchymal transitions (EMTs). Interclonal cooperativity occurs when cancer cell-cancer cell interactions produce an emergent malignant phenotype from individually non-malignant clones. In interclonal cooperativity, the oncogenic mutations occur in different clones within the tumour that complement each other and cooperate in order to drive progression. This reconciles the accepted genetic and evolutionary basis of cancers with the observed polyclonality in tumours. Here, we provide a conceptual basis for examining the importance of cancer cell-cancer cell interactions to the behaviour of tumours and propose specific mechanisms by which clonal diversity in tumours, including that provided by EMTs, can drive the progression of tumours to malignancy. Cancer Council NSW Sydney Cancer Centre Foundation

Daylight-mediated photodynamic therapy (DL-PDT) is considered as effective as conventional PDT using artificial light (light-emitting diode (LED)-PDT) for treatment of actinic keratoses (AK). This randomized prospective non-sponsored study assessed the cost-effectiveness of DL-PDT compared with LED-PDT. Seventy patients with 210 AKs were randomized to DL-PDT or LED-PDT groups. Effectiveness was assessed at 6 months. The costs included societal costs and private costs, including the time patients spent in treatment. Results are presented as incremental cost-effectiveness ratio (ICER). The total costs per patient were significantly lower for DL-PDT ((sic) 132) compared with LED-PDT ((sic) 170), giving a cost saving of (sic)38 (p = 0.022). The estimated probabilities for patients' complete response were 0.429 for DL-PDT and 0.686 for LED-PDT; a difference in probability of being healed of 0.257. ICER showed a monetary gain of (sic) 147 per unit of effectiveness lost. DL-PDT is less costly and less effective than LED-PDT. In terms of cost-effectiveness analysis, DL-PDT provides lower value for money compared with LED-PDT.

Vismodegib, a highly selective inhibitor of hedgehog (Hh) pathway, is an approved treatment for basal-cell carcinoma. Patients on treatment with vismodegib often report profound alterations in taste sensation. The cellular mechanisms underlying the alterations have not been studied. Sonic Hh (Shh) signaling is required for cell growth and differentiation. In taste buds, Shh is exclusively expressed in type IV taste cells, which are undifferentiated basal cells and the precursors of the three types of taste sensing cells. Thus, we investigated if vismodegib has an inhibitory effect on taste cell turnover because of its known effects on Hh signaling. We gavaged C57BL/6J male mice daily with either vehicle or 30 mg/kg vismodegib for 15 weeks. The gustatory behavior and immunohistochemical profile of taste cells were examined. Vismodegib-treated mice showed decreased growth rate and behavioral responsivity to sweet and bitter stimuli, compared to vehicle-treated mice. We found that vismodegib-treated mice had significant reductions in taste bud size and numbers of taste cells per taste bud. Additionally, vismodegib treatment resulted in decreased numbers of Ki67- and Shh-expressing cells in taste buds. The numbers of phospholipase Cβ2- and α-gustducin-expressing cells, which contain biochemical machinery for sweet and bitter sensing, were reduced in vismodegib-treated mice. Furthermore, vismodegib treatment resulted in reduction in numbers of T1R3, glucagon-like peptide-1, and glucagon-expressing cells, which are known to modulate sweet taste sensitivity. These results suggest that inhibition of Shh signaling by vismodegib treatment directly results in alteration of taste due to local effects in taste buds.

In a long-term cohort study, we calculated cancer incidences and survival rates after the development of these cancers in kidney-transplant recipients. The cancer incidences were compared with those in the general population. The occurrence of cancer was recorded in all patients who received kidney transplantation between 1966 and 2006. The median follow-up time was more than 9 years with a maximum of almost 40 years. Altogether 327 (17%) of 1906 patients developed cancer after transplantation: 142 (7%) had non-cutaneous malignancies; 178 (9%) cutaneous squamous-cell carcinomas and 138 (7%) basal-cell carcinomas. The cumulative incidence of any cancer was 13%, 33% and 47% after 10, 20 and 30 years, respectively. The incidences of cancers of the oral cavity, stomach, female genital organs, kidney, thyroid gland, leukemias and lymphomas, and cutaneous squamous-cell carcinoma were significantly increased with a highest standardized morbidity ratio of 40 for cutaneous squamous-cell carcinomas. Survival rates after non-cutaneous malignancies were 57%, 43% and 36% and after non-melanocytic skin cancer 99%, 90% and 77% after 1, 3 and 5 years, respectively. The increased incidence of non-cutaneous malignancies after kidney transplantation is associated with a high mortality. Prevention of cancer after kidney transplantation should be a major focus of future research.

Since 2007, genome-wide association (GWA) studies have identified numerous well-supported, novel genetic risk loci for common cancers; however, there are concerns that this technology is reaching its limits. We provide an overview of GWA-identified genetic associations with solid tumors. We simulated the distribution of population risk alleles for colorectal, prostate, testicular, and thyroid cancers based on genetic variants identified in GWA studies. We also evaluated whether statistical power to detect typical genetic effects could be improved with studies performing GWA analyses of all available samples rather than multistage designs. Fifty-six eligible articles yielded 92 eligible associations between cancer phenotypes and genetic variants with a median per-allele odds ratio (OR) of 1.22 (interquartile range = 1.15-1.36). Half of the associations pertained to prostate, colorectal, or breast cancer. Individuals at the upper quartile of simulated risk had only 2.1- to 4.2-fold higher relative risk than those in the lower quartile. Comprehensive evaluation of currently available samples with GWA platforms would yield few additional variants with per-allele OR = 1.4, but many more variants with OR = 1.2 could be detected; statistical power to detect weak associations (OR = 1.07) would still be negligible. The GWA approach is effective in identifying common genetic variants with moderate effect; however, identifying loci with very small effects and rare variants will require major new efforts. At present, the utility of GWA-identified risk loci in risk stratification for cancer is limited. J Natl Cancer Inst

To investigate the associations between intake of antioxidant nutrients and risk of basal cell (BCC) and squamous cell carcinomas (SCC) of the skin, we carried out a prospective study among 1001 randomly selected adults living in an Australian community. Intake of antioxidants was estimated in 1996. Incident, histologically-confirmed BCC and SCC were recorded between 1996 and 2004. High dietary intake of lutein and zeaxanthin was associated with a reduced incidence of SCC in persons who had a history of skin cancer at baseline (highest versus lowest tertile, multivariable adjusted relative risk (RR) = 0.47, 95% confidence interval (CI): 0.25¿0.89; P for trend = 0.02). In persons without a history of skin cancer at baseline, development of BCC was positively associated with intake of vitamins C and E from foods plus supplements (RR = 3.1, 95% CI: 1.1¿8.6; P for trend = 0.03 and RR = 2.6, 95% CI: 1.1¿6.3; P for trend = 0.02, respectively). In those with a skin cancer history at baseline, dietary intake in the second tertile for ß-carotene (multivariable adjusted RR = 2.2, 95% CI: 1.2¿4.1) and for vitamin E (multivariable adjusted RR = 2.1, 95% CI: 1.1¿3.9) was associated with increased BCC risk, with no trend, and similar results were seen in those with a specific history of BCC. These data suggest quite different associations between antioxidant intake and SCC compared with BCC, consistent with other evidence of their different causal pathways.

International audience; We directly compared risk factors between 214 histologically confirmed melanomas (CMM), 215 basal-cell carcinomas (BCC) and 139 squamous-cell carcinomas (SCC) in a multiple case-case-control study with 349 controls from patients without dermatological disease admitted to the same hospitals. Subjects with fair hair had a significant risk increase for all types of tumours at a comparable level (OR(adj) for blonde hair: CMM 2.3; SCC 2.4; BCC 2.3). The effect of pale eyes was significant and similar for CMM and BCC (OR(adj) 2.6). Intermittent sun exposure measured in hours spent at beach during holidays was significant for both CMM (OR(adj) 2.6 for more than 7000 lifelong hours) and BCC (OR(adj) 2.1 for more than 7000 lifelong hours), while SCC exhibited a significant risk increase for chronic exposure to sunlight measured in hours of outdoor work (OR(adj) 2.2 for more than 6000 lifelong hours). In the case-case comparison using a multinomial logistic regression model, we found a statistically significant risk difference for pale eyes, and number of naevi in the CMM group, compared to other skin cancers. For intermittent sun exposure, there was a significant risk difference of BCC when compared to the risk of SCC. Factors influencing risk of SCC are different, with chronic exposure to sun playing a major role in causing this type of carcinoma.

Background: Acute effects of UV irradiation include UV-induced erythema. Sunlight plays an important role in the development of skin cancer. Several predictive factors of UV-induced erythema could also be predictive for skin cancer. Objective: Our objective was to quantitatively assess phenotypical and nutritional determinants of sensitivity to UV irradiation, as assessed by the minimal erythema dose (MED). Design: We conducted a cross-sectional study among 335 volunteers. Sensitivity to UV irradiation was established through assessment of the MED. Phenotypical determinants, including skin melanin content, hair color and iris color were determined by skin reflectance spectrometry, a subjective questionnaire and an objective classification system, respectively. Furthermore, dietary exposure was measured by carotenoids, vitamin C, retinol and alpha-tocopherol in serum. Results: Male subjects were found to be more sensitive to UV irradiation; that is, the MED was significantly lower compared to female subjects. Skin melanin content, which was positively associated with iris color in both sexes and with hair color in men, was the main phenotypical determinant of sensitivity to UV irradiation. No associations were found between serum carotenoids and MED in the total study group. Vitamin C was inversely associated with MED. However, associations between carotenoids concentrations and MED showed a positive trend in subjects with melanin values above and a negative trend in subjects below the median after adjustment for gender and total cholesterol. Conclusions: Skin melanin content and gender are important determinants of sensitivity to UV irradiation. No relation was found between serum carotenoids and MED in the total study group. The inverse association between vitamin C and MED was against our hypothesis. For the modifying effect of melanin on the association between carotenoids and MED, we do not have a clear biological explanation.

The hair follicle and the nail share similar embryological and anatomical features and the occurrence of a tumour with follicular differentiation in the nail further demonstrates the common origin of these adnexal structures. Onychoblastoma has never been reported in the literature and probably represents a type of onychomatricoma, a term which includes a spectrum of different neoplasms with a similar architecture

The Nevoid Basal-Cell Carcinoma Syndrome (NBCC), or as it is also referred to, basal-cell nevus syndrome or Gorlin-Goltz syndrome, is characterized by multiple early-appearing basal cell carcinomas, keratocytosis of the mandible, and anomalies of the ocular, skeletal reproductive system. We describe four patients in the same family, all of them possessing a large number of skin tumors associated with other typical clinical and X-Ray anomalies of NBCC. The definitive treatment of NBCC has yet to be established, however, early diagnosis is very important as well as the periodical follow-up examination of ten patients, mainly due to the transformations in the skin lesions that may occur. INTRODUÇÃO: A Síndrome do Nevo Basocelular (SNBC), também chamada de Síndrome do Carcinoma Nevóide Basocelular ou Síndrome de Gorlin-Goltz, caracteriza-se por múltiplos carcinomas basocelulares de aparecimento precoce, cistos em mandíbula, além de outras anomalias como as ósseas, problemas oculares e no aparelho reprodutivo. CONCLUSÃO: O tratamento definitivo da SNBC ainda não foi bem estabelecido, porém ressalta-se a importância do diagnóstico precoce, além do seguimento periódico dos pacientes, principalmente devido às transformações das lesões da pele que podem ocorrer.