Defining the Validity of Skin Self-Examination as a Screening Test for the Detection of Suspicious Pigmented Lesions: A Meta-Analysis of Diagnostic Test Accuracy.

BACKGROUND: Skin self-examination (SSE) is widely promoted for the detection of suspicious pigmented lesions. However, determining screening accuracy is essential to appraising the usefulness of SSE. OBJECTIVES: The aim of this work was to pool estimates from studies of SSE diagnostic accuracy in the detection of suspicious pigmented lesions. METHODS: This study was registered with PROSPERO (CRD42021246356) and conducted in accordance with PRISMA-DTA guidelines. A systematic search of Medline (PubMed) EMBASE, CINAHL, and The Cochrane Library was conducted to identify relevant studies. We included studies that examined the accuracy of SSE, either whole-body or site-specific, for detecting change in individual pigmented lesions or detecting an atypical naevus. A univariate random-effects model, based on logit-transformed data, was used to calculate a summary diagnostic odds ratio (DOR) as well as pooled sensitivity and specificity. Cochran's Q test and the I2 statistic were calculated to assess heterogeneity. A proportional hazards model was used to calculate the area under the curve (AUC) and plot the summary receiver operator characteristic curve. We used the Quality Assessment of Diagnostic Accuracy Studies-2 tool to grade study quality. RESULTS: We identified 757 studies, of which 3 met inclusion criteria for quantitative synthesis. The pooled sensitivity and specificity based on 553 included participants was 59 and 82%, respectively. The summary DOR was 5.88 and the AUC was 0.71. There were some concerns regarding risk of bias in all 3 studies. CONCLUSIONS: SSE can detect suspicious pigmented lesions with reasonable sensitivity and relatively high specificity, with the AUC suggesting acceptable discriminatory ability.

The development and validation of a decision aid to facilitate patient choice of surgery versus radiotherapy for high-risk basal cell carcinoma.

Basal cell carcinoma (BCC) is an increasingly common cancer. For high-risk BCCs, there are several treatment options, with similar efficacies. The current best practice in deciding upon a particular treatment is for a patient-centred approach. At present, there are few resources available for patients to assist their choice. This reduces patient autonomy and increases the burden on clinicians within clinic. Patient decision aids (PDAs) have been shown to increase patient autonomy and facilitate shared decision-making. Currently, there is no published PDA designed to facilitate the decision between surgical management or radiotherapy in high-risk BCCs. We developed a novel decision aid designed along the International Patient Decision Aid Standards to fill this clinical need, and evaluated its acceptance by both patients and clinicians. We describe the challenges faced at initial alpha and subsequent beta testing, and go on to validate our PDA with both the Decisional Conflict Scale and the nine-item Shared Decision Making Questionnaire (SDMQ9). We include an example of the PDA and encourage other units to modify the PDA for their own use.

Omega-3 fatty acid intake and decreased risk of skin cancer in organ transplant recipients.

PURPOSE: Organ transplant recipients have over 100-fold higher risk of developing skin cancer than the general population and are in need of further preventive strategies. We assessed the possible preventive effects of omega-3 polyunsaturated fatty acid (PUFA) intake from food on the two main skin cancers, squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) in kidney and liver transplant recipients. METHODS: Adult kidney or liver transplant recipients transplanted for at least 1 year and at high risk of skin cancer were recruited from the main transplant hospital in Queensland, 2012-2014 and followed until mid-2016. We estimated their dietary total long-chain omega-3 PUFAs and α-linolenic acid intakes at baseline using a food frequency questionnaire and ranked PUFA intakes as low, medium, or high. Relative risks (RRsadj) of skin cancer adjusted for confounding factors with 95% confidence intervals (CIs) were calculated. RESULTS: There were 449 transplant recipients (mean age, 55 years; 286 (64%) male). During follow-up, 149 (33%) patients developed SCC (median 2/person; range 1-40) and 134 (30%), BCC. Transplant recipients with high total long-chain omega-3 PUFA compared with low intakes showed substantially reduced SCC tumour risk (RRadj 0.33, 95% CI 0.18-0.60), and those with high α-linolenic acid intakes experienced significantly fewer BCCs (RRadj 0.40, 95% CI 0.22-0.74). No other significant associations were seen. CONCLUSION: Among organ transplant recipients, relatively high intakes of long-chain omega-3 PUFAs and of α-linolenic acid may reduce risks of SCC and BCC, respectively.

Is methotrexate hepatotoxicity associated with cumulative dose? A systematic review and meta-analysis.

BACKGROUND/OBJECTIVE: Methotrexate (MTX) is widely used in various medical specialties. However, hepatotoxicity is an ongoing concern and this is thought to be directly associated with cumulative dose. We sought to synthesise the published literature to evaluate the association between methotrexate hepatotoxicity and cumulative dose. METHODS: A systematic review of Medline (PubMed) EMBASE, CINAHL and The Cochrane Library was performed. Full texts of articles were examined, and excluded articles were recorded with reasons for exclusion. A meta-analysis of correlation coefficients was performed using Fisher's z-transformation and a random effects model. Cochran's Q-test and the I2 statistic were calculated to assess heterogeneity. RESULTS: A total of 35 studies met inclusion criteria. Measures of hepatotoxicity were highly varied and included liver biopsy, elastography, FibroTest, biochemical tests and scoring systems (Fib-4, APRI, AST:ALT). Some studies analysed for the association with MTX cumulative dose using more than one modality. Overall, 38 analyses found no significant association between MTX cumulative dose and hepatoxicity vs eight that identified a significant association. The pooled correlation coefficient from five studies which utilised elastography was 0.18 (95% CI, -0.09 to 0.42), with significant heterogeneity between studies (P < 0.0001), I2  = 92%). CONCLUSIONS: Our synthesis of a large volume of studies in this review found no significant association between MTX cumulative dose and hepatotoxicity, both in terms of vote counting and with regard to the meta-analysis of correlation coefficients from studies that utilised elastography. This challenges the long-held belief that liver injury is a direct result of drug accumulation.

Incidence and Regression of Actinic Keratoses in Organ Transplant Recipients.

Actinic keratoses (AKs) are highly dynamic lesions and AK activity has been shown to be associated with squamous cell carcinoma (SCC). We sought to explore risk factors which may affect the 12-month turnover of AKs in organ transplant recipients (OTRs). The number of incident AKs, regressed AKs and net change in AK counts were calculated. Negative binomial regression and Poisson regression models were used to estimate rate ratios (RR) for these 3 outcomes. Among 150 renal and 89 liver OTRs, those who spent > 50% of a typical weekday in the sun had a lower rate of AK regression than those who spent minimal time in the sun during a typical weekday. Age, parents' country of origin, hair colour, skin cancer history and recent AK treatment were all significantly associated with AK turnover. Clinically, these risk factors may be used to monitor OTRs at increased risk of SCC.

Assessing the Concordance of Actinic Keratosis Counts on Digital Photographs with Clinical Examination in Organ Transplant Recipients.

Actinic keratoses (AKs) are common lesions that are usually diagnosed clinically. We sought to examine the accuracy of AK counts on digital photographs when compared with clinical examination counts. Skin sites of renal transplant recipients were examined clinically and on digital photographs by independent dermatologically-trained examiners. Specificity, sensitivity and Kendall's tau-b correlation coefficient were calculated based on exact photographic AK counts as well as counts with ± 1 AK tolerance. When 138 skin sites with 305 clinical AK counts were examined for total count ± 1 AK, the sensitivity and specificity of photography was 95% and 100%, respectively. There was significant positive correlation between AK counts on photographs and clinical examination (Ƭb = 0.537) and correlation was even higher for total count ± 1 AK (Ƭb = 0.758). The results show moderate to strong concordance between AK counts on digital photographs and on clinical examination.

Interventions for vitiligo.

BACKGROUND: Vitiligo is a chronic skin disorder characterised by patchy loss of skin colour. Some people experience itching before the appearance of a new patch. It affects people of any age or ethnicity, more than half of whom develop it before the age of 20 years. There are two main types: generalised vitiligo, the common symmetrical form, and segmental, affecting only one side of the body. Around 1% of the world's population has vitiligo, a disease causing white patches on the skin. Several treatments are available. Some can restore pigment but none can cure the disease. OBJECTIVES: To assess the effects of all therapeutic interventions used in the management of vitiligo. SEARCH METHODS: We updated our searches of the following databases to October 2013: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library (2013, Issue 10), MEDLINE, Embase, AMED, PsycINFO, CINAHL and LILACS. We also searched five trials databases, and checked the reference lists of included studies for further references to relevant randomised controlled trials (RCTs). SELECTION CRITERIA: Randomised controlled trials (RCTs) assessing the effects of treatments for vitiligo. DATA COLLECTION AND ANALYSIS: At least two review authors independently assessed study eligibility and methodological quality, and extracted data. MAIN RESULTS: This update of the 2010 review includes 96 studies, 57 from the previous update and 39 new studies, totalling 4512 participants. Most of the studies, covering a wide range of interventions, had fewer than 50 participants. All of the studies assessed repigmentation, however only five reported on all of our three primary outcomes which were quality of life, > 75% repigmentation and adverse effects. Of our secondary outcomes, six studies measured cessation of spread but none assessed long-term permanence of repigmentation resulting from treatment at two years follow-up.Most of the studies assessed combination therapies which generally reported better results. New interventions include seven new surgical interventions.We analysed the data from 25 studies which assessed our primary outcomes. We used the effect measures risk ratio (RR), and odds ratio (OR) with their 95% confidence intervals (CI) and where N is the number of participants in the study.We were only able to analyse one of nine studies assessing quality of life and this showed no statistically significant improvement between the comparators.Nine analyses from eight studies reported >75% repigmentation. In the following studies the repigmentation was better in the combination therapy group: calcipotriol plus PUVA (psoralen with UVA light) versus PUVA (paired OR 4.25, 95% CI 1.43 to 12.64, one study, N = 27); hydrocortisone-17-butyrate plus excimer laser versus excimer laser alone (RR 2.57, 95% CI 1.20 to 5.50, one study, N = 84); oral minipulse of prednisolone (OMP) plus NB-UVB (narrowband UVB) versus OMP alone (RR 7.41, 95% CI 1.03 to 53.26, one study, N = 47); azathioprine with PUVA versus PUVA alone (RR 17.77, 95% CI 1.08 to 291.82, one study, N = 58) and 8-Methoxypsoralen (8-MOP ) plus sunlight versus psoralen (RR 2.50, 95% CI 1.06 to 5.91, one study, N = 168). In these three studies ginkgo biloba was better than placebo (RR 4.40, 95% CI 1.08 to 17.95, one study, N = 47); clobetasol propionate was better than PUVAsol (PUVA with sunlight) (RR 4.70, 95% CI 1.14 to 19.39, one study, N = 45); split skin grafts with PUVAsol was better than minipunch grafts with PUVAsol (RR 1.89, 95% CI 1.25 to 2.85, one study, N = 64).We performed one meta-analysis of three studies, in which we found a non-significant 60% increase in the proportion of participants achieving >75% repigmentation in favour of NB-UVB compared to PUVA (RR 1.60, 95% CI 0.74 to 3.45; I² = 0%).Studies assessing topical preparations, in particular topical corticosteroids, reported most adverse effects. However, in combination studies it was difficult to ascertain which treatment caused these effects. We performed two analyses from a pooled analysis of three studies on adverse effects. Where NB-UVB was compared to PUVA, the NB-UVB group reported less observations of nausea in three studies (RR 0.13, 95% CI 0.02 to 0.69; I² = 0% three studies, N = 156) and erythema in two studies (RR 0.73, 95% CI 0.55 to 0.98; I² = 0%, two studies, N = 106), but not itching in two studies (RR 0.57, 95% CI 0.20 to 1.60; I² = 0%, two studies, N = 106).Very few studies only assessed children or included segmental vitiligo. We found one study of psychological interventions but we could not include the outcomes in our statistical analyses. We found no studies evaluating micropigmentation, depigmentation, or cosmetic camouflage. AUTHORS' CONCLUSIONS: This review has found some evidence from individual studies to support existing therapies for vitiligo, but the usefulness of the findings is limited by the different designs and outcome measurements and lack of quality of life measures. There is a need for follow-up studies to assess permanence of repigmentation as well as high- quality randomised trials using standardised measures and which also address quality of life.

Cutaneous manifestations of myelodysplastic syndrome: A systematic review.

Myelodysplastic syndrome (MDS) may present with specific skin lesions, such as leukaemia cutis, which is a well known poor prognostic marker of leukaemia with a high risk of acute leukaemic transformation. However, less is known regarding non-specific cutaneous manifestations of MDS including the prevalence, types and their prognostic and therapeutic significance, which we aimed to determine through this systematic review. We searched electronic databases (PubMed, Medline and EMBASE) from inception up to 26 January 2023 for studies reporting cutaneous manifestations of MDS. Eighty eight articles (case reports n = 67, case series n = 21), consisting of 134 patients were identified. We identified 6 common cutaneous manifestations: neutrophilic dermatoses (n = 64), vasculitis (n = 21), granulomatous (n = 8), connective tissue disease (CTD) (n = 7; composed of dermatomyositis (n = 5), cutaneous lupus erythematosus (n = 1), and systemic sclerosis (n = 1)), panniculitis (n = 4), immunobullous (n = 1), and other (n = 29). Cutaneous features either occurred at time of MDS diagnosis in 25.3%, preceding the diagnosis in 34.7% (range 0.5-216 months), or after diagnosis in 40.0% (range 1-132 months). Prognosis was poor (40.2% death) with 34.1% progressing to acute myeloid leukaemia (AML). 50% of those with MDS who progressed to AML had neutrophilic dermatoses (p = 0.21). Myelodysplastic syndrome was fatal in 39.2% of neutrophilic dermatoses (median time from onset of cutaneous manifestation: 12 months), 50% of vasculitis (7.5 months), 62.5% of granulomatous (15.5 months) and 14.3% of CTD (7 months). Recognition of patterns of cutaneous features in MDS will improve early diagnosis and risk stratification according to subtype and associated prognosis.

The development and validation of a decision aid to enhance shared decision-making for the management of actinic keratosis.

Actinic keratoses (AKs) are common pre-malignant lesions. There are numerous management options including active surveillance, multiple topical therapies, cryotherapy, curettage and cautery, and photodynamic therapy, each with their own risks, benefits and efficacy. Best practice currently involves shared decision-making between patient and clinician, particularly in the setting of multiple management options. Patient decision aids have been shown to be beneficial in the shared decision-making process. In view of this, we have developed and validated a decision aid for the management of AKs, in concordance with the International Patient Decision Aids Standards.

Basal cell carcinomas in organ transplant recipients versus the general population: clinicopathologic study.

Organ transplant recipients (OTRs) are at greater risk of basal cell carcinomas (BCCs) than non-OTRs, but histopathologic differences between BCCs in OTRs and the general population are largely unknown. We compared clinicopathologic features of BCCs in OTRs vs the general population in Queensland, Australia. Details of BCC tumors (site, size, level of invasion, subtype, biopsy procedure) were collected from histopathology reports in two prospective skin cancer studies, one in OTRs and one general-population-based. We used log-binomial regression models to estimate age- and sex-adjusted prevalence ratios (PR) with 95% confidence intervals (CIs) for BCC features. Overall, there were 702 BCCs in 200 OTRs and 1725 BCCs in 804 population cases. Of these, 327 tumors in 128 OTRs were higher risk BCCs (any head and neck BCC; ≥ 2 cm on trunk/extremities), more per person than 703 higher risk BCCs in 457 cases in the general population (chi-square p = 0.008). Among head/neck BCCs, OTRs were more likely than general population cases to have BCCs on scalp/ear than on face/lip/neck (PR = 1.5, 95%CI 1.2-1.8). Although aggressive subtypes were less common among higher risk BCCs in OTRs, BCCs invading beyond the dermis were almost twice as prevalent in OTRs (PR = 1.8, 95% CI 1.3-2.6) than the general population.

High-risk Prognostic Tumor Features of Squamous Cell Carcinomas in Organ Transplant Recipients Compared With the General Population.

Importance: The extent to which major high-risk features of squamous cell carcinomas (SCCs) in organ transplant recipients (OTRs) differ from SCCs in the general population is not known. Objective: To quantify the relative frequency of perineural invasion, invasion below the dermis, lack of cellular differentiation, and tumor diameter greater than 20 mm in SCCs in OTRs and the general population, by anatomic site. Design, Setting, and Participants: This dual-cohort study in Queensland, Australia, included a cohort of OTRs at high risk of skin cancer ascertained from 2012 to 2015 (Skin Tumours in Allograft Recipients [STAR] study) and a population-based cohort ascertained from 2011 (QSkin Sun and Health Study). The STAR study comprised population-based lung transplant recipients and kidney and liver transplant recipients at high risk of skin cancer recruited from tertiary centers and diagnosed with histopathologically confirmed SCC from 2012 to 2015. The QSkin participants were recruited from Queensland's general adult population, and primary SCCs diagnosed from 2012 to 2015 were ascertained through Medicare (national health insurance scheme) and linked with histopathology records. Data analysis was performed from July 2022 to April 2023. Main Outcomes and Measures: Prevalence ratio (PR) of head/neck location, perineural invasion, tumor invasion to/beyond subcutaneous fat, poor cellular differentiation, and tumor diameter greater than 20 mm among SCCs in OTRs vs the general population. Results: There were 741 SCCs excised from 191 OTRs (median [IQR] age, 62.7 [56.7-67.1] years; 149 [78.0%] male) and 2558 SCCs from 1507 persons in the general population (median [IQR] age, 63.7 [58.0-68.8] years; 955 [63.4%] male). The SCCs developed most frequently on the head/neck in OTRs (285, 38.6%), but on arms/hands in the general population (896, 35.2%) (P < .001). After adjusting for age and sex, perineural invasion was more than twice as common in OTRs as in population cases (PR, 2.37; 95% CI, 1.70-3.30), as was invasion to/beyond subcutaneous fat (PR, 2.37; 95% CI, 1.78-3.14). Poorly vs well-differentiated SCCs were more than 3-fold more common in OTRs (PR, 3.45; 95% CI, 2.53-4.71), and prevalence of tumors greater than 20 mm vs 20 mm or smaller was moderately higher in OTRs (PR, 1.52; 95% CI, 1.08-2.12). Conclusions and Relevance: In this dual-cohort study, SCCs in OTRs had significantly worse prognostic features than SCCs in the general population, reinforcing the necessity of early diagnosis and definitive management of SCCs in OTRs.

Destructive and topical treatments of skin lesions in organ transplant recipients and relation to skin cancer.

Various treatments of keratotic skin lesions and early skin cancers are performed in organ transplant recipients (OTRs) at high risk of skin malignancies but the frequency of their use is unknown. We prospectively assessed the frequency of use of cryotherapy, diathermy, and topical therapies and also investigated their associations with background incidence of histologically-confirmed squamous-cell carcinoma (SCC) and basal cell carcinoma (BCC) in a cohort of OTRs in Queensland, Australia. Median follow-up ranged from 1.7 to 3.2 years across organ transplant groups. Among 285 kidney, 125 lung and 203 liver transplant recipients [382 (62%) male, 380 (62%) immunosuppressed > 5 years, 394 (64%) previously diagnosed with skin cancer], 306 (50%) reported treatment of skin lesions with major types of non-excision therapies during follow-up: 278 (45%) cryotherapy or diathermy; 121 (20%) topical treatments. Of these 306, 150 (49%) developed SCC at double the incidence of those who did not receive these treatments, as assessed by incidence rate ratio (IRR) adjusted for age, sex, type of organ transplant, skin color and history of skin cancer at baseline, calculated by multivariable Poisson regression (IRRadj = 2.1, 95% confidence interval (CI) 1.4-3.1). BCC incidence was not associated with these therapies. Skin lesions in OTRs that are treated with cryotherapy, diathermy, or topical treatment warrant judicious selection and careful follow-up.