Benefits of a brief psychological intervention targeting fear of cancer recurrence in people at high risk of developing another melanoma: 12-month follow-up results of a randomized controlled trial.

BACKGROUND: People with melanoma want and need effective interventions for living with fear of cancer recurrence (FCR). OBJECTIVES: This study reports the 12-month outcomes of a brief, psychological intervention designed to reduce FCR in people at high risk of developing another primary melanoma compared with usual care. METHODS: In this two-arm randomized controlled trial, adults previously diagnosed with stage 0, I or II melanoma were randomly allocated to the intervention (n = 80) or control (usual care) arm (n = 84). The trial was registered with the Australian and New Zealand Clinical Trials Registry on 19 March 2013 (registration: ACTRN12613000304730). The intervention comprised a 76-page psychoeducational resource and three individually tailored, telephone-based sessions with a psychologist, scheduled at specific time points around participants' dermatological appointments. The primary outcome was the level of self-reported fear of new or recurrent melanoma assessed at 12 months postintervention using the severity subscale of the Fear of Cancer Recurrence Inventory. RESULTS: Compared with the control arm, the intervention group reported significantly lower FCR at 12 months postintervention; the between-group mean difference was -1·41 for FCR severity [95% confidence interval (CI) -2·6 to -0·2; P = 0·02] and -1·32 for FCR triggers (95% CI -2·6 to -0·02; P = 0·04). The odds ratio for FCR severity scores ≥13 (54% intervention, 63% control) was 0·59 (95% CI 0·30-1·14, P = 0·12). There were no differences between groups in secondary outcomes, such as anxiety, depression or health-related quality of life. CONCLUSIONS: The previously reported 6-month benefits of this brief, patient-centred psychological intervention in reducing FCR were found to continue 12 months postintervention, with no known adverse effects, supporting implementation as part of routine melanoma care.

Standardization of dermoscopic terminology and basic dermoscopic parameters to evaluate in general dermatology (non-neoplastic dermatoses): an expert consensus on behalf of the International Dermoscopy Society.

BACKGROUND: Over the last few years, several articles on dermoscopy of non-neoplastic dermatoses have been published, yet there is poor consistency in the terminology among different studies. OBJECTIVES: We aimed to standardize the dermoscopic terminology and identify basic parameters to evaluate in non-neoplastic dermatoses through an expert consensus. METHODS: The modified Delphi method was followed, with two phases: (i) identification of a list of possible items based on a systematic literature review and (ii) selection of parameters by a panel of experts through a three-step iterative procedure (blinded e-mail interaction in rounds 1 and 3 and a face-to-face meeting in round 2). Initial panellists were recruited via e-mail from all over the world based on their expertise on dermoscopy of non-neoplastic dermatoses. RESULTS: Twenty-four international experts took part in all rounds of the consensus and 13 further international participants were also involved in round 2. Five standardized basic parameters were identified: (i) vessels (including morphology and distribution); (ii) scales (including colour and distribution); (iii) follicular findings; (iv) 'other structures' (including colour and morphology); and (v) 'specific clues'. For each of them, possible variables were selected, with a total of 31 different subitems reaching agreement at the end of the consensus (all of the 29 proposed initially plus two more added in the course of the consensus procedure). CONCLUSIONS: This expert consensus provides a set of standardized basic dermoscopic parameters to follow when evaluating inflammatory, infiltrative and infectious dermatoses. This tool, if adopted by clinicians and researchers in this field, is likely to enhance the reproducibility and comparability of existing and future research findings and uniformly expand the universal knowledge on dermoscopy in general dermatology. What's already known about this topic? Over the last few years, several papers have been published attempting to describe the dermoscopic features of non-neoplastic dermatoses, yet there is poor consistency in the terminology among different studies. What does this study add? The present expert consensus provides a set of standardized basic dermoscopic parameters to follow when evaluating inflammatory, infiltrative and infectious dermatoses. This consensus should enhance the reproducibility and comparability of existing and future research findings and uniformly expand the universal knowledge on dermoscopy in general dermatology.

A re-evaluation of teenage sunbed use following the introduction of banning legislation for under 18-year-olds.

BACKGROUND: There is little information on the effectiveness of introducing age restriction legislation alone to reduce the rate of sunbed usage by teenagers. Prior to the Public Health (Sunbed) Act of 2014 prohibiting the use of sunbeds in under 18-year-olds in Ireland we reported the rate of sunbed use at 7.5%. OBJECTIVES: The aim of the study was to compare the rate of sunbed usage among Irish teenagers before and after the introduction of banning legislation to determine if it had the desired effect of reducing its rate of use. METHODS: In a cross-sectional survey, students from the same schools as in our previous study completed an anonymous, written questionnaire pertaining to sunbed usage. RESULTS: In total, 783 questionnaires, from 13 schools across Ireland, were completed. The rate of sunbed use in the current study was 7.2%, compared to 7.5% in the pre-ban study, (P = 0.76). A higher rate of sunbed use was observed in Dublin schools and female public students. CONCLUSION: Our study suggests that legislation alone is ineffective at reducing sunbed usage in a teenage population. A multifaceted approach is required that includes enforcement of the legislation together with targeted public education and awareness campaigns using all aspects of the media.

Dermatoscopic features of thin (≤2 mm Breslow thickness) vs. thick (>2 mm Breslow thickness) nodular melanoma and predictors of nodular melanoma versus nodular non-melanoma tumours: a multicentric collaborative study by the International Dermoscopy Society.

BACKGROUND: Thin nodular melanoma (NM) often lacks conspicuous melanoma-specific dermatoscopic criteria and escapes clinical detection until it progresses to a thicker and more advanced tumour. OBJECTIVE: To investigate the dermatoscopic morphology of thin (≤2 mm Breslow thickness) vs. thick (>2 mm) NM and to identify dermatoscopic predictors of its differential diagnosis from other nodular tumours. METHODS: Retrospective, morphological case-control study, conducted on behalf of the International Dermoscopy Society. Dermatoscopic images of NM and other nodular tumours from 19 skin cancer centres worldwide were collected and analysed. RESULTS: Overall, 254 tumours were collected (69 NM of Breslow thickness ≤2 mm, 96 NM >2 mm and 89 non-melanoma nodular lesions). Light brown coloration (50.7%) and irregular brown dots/globules (42.0%) were most frequently observed in ≤2 mm NMs. Multivariate analysis revealed that dotted vessels (3.4-fold), white shiny streaks (2.9-fold) and irregular blue structureless area (2.4-fold) were predictors for thinner NM compared to non-melanoma nodular tumours. Overall, irregular blue structureless area (3.4-fold), dotted vessels (4.6-fold) and serpentine vessels (1.9-fold) were predictors of all NM compared to non-melanoma nodular lesions. LIMITATIONS: Absence of a centralized, consensus pathology review and cases selected form tertiary centres maybe not reflecting the broader community. CONCLUSIONS: Our study sheds light into the dermatoscopic morphology of thin NM in comparison to thicker NM and could provide useful clues for its differential diagnosis from other non-melanoma nodular tumours.

Declining incidence of keratinocyte carcinoma in organ transplant recipients.

BACKGROUND: All organ transplant populations are predisposed to increased rates of keratinocyte carcinoma (KC). Since this increased risk was first appreciated, immunosuppressive regimens have changed and organ transplant recipients (OTRs) have been aggressively screened for KC. There is a perception that these measures have impacted on KC incidence but there is a paucity of population-based studies on post-transplant rates of basal cell carcinoma (BCC). OBJECTIVES: To identify trends in incidence rates for KC following solid organ transplantation over the past two decades. METHODS: This nationwide, population-based study included all solid OTRs transplanted between 1994 and 2014. Patient data were matched to national cancer registry data to determine the standardized incidence ratio (SIR) of KC in solid OTRs compared with the general population. RESULTS: In total 3580 solid OTRs were included. The total follow-up time was 28 407 person-years (median follow-up 7·11 years). The overall SIRs for squamous cell carcinoma (SCC) and BCC were 19·7 and 7·0, respectively. Our study documents a progressive fall in the SIRs for SCC and BCC from peak SIRs (95% confidence intervals) in 1994-1996 of 26·4 (21·5-32·4) and 9·1 (7·4-11·3) to 6·3 (2·3-16·7) and 3·2 (1·4-7·1) in 2012-2014, respectively. The ratio of SCC to BCC has remained at 3 to 1 over the last two decades. CONCLUSIONS: Our study is the first to demonstrate a significant reduction over the past two decades in the incidences of both SCC and BCC following solid organ transplantation. The SCC-to-BCC ratio was maintained, demonstrating that both are reducing equally. This trend coincided with temporal changes in immunosuppressive protocols and the introduction of skin cancer prevention programmes. What's already known about this topic? Prior studies have shown that the risk of cutaneous squamous cell carcinoma (SCC) has declined over recent decades following solid organ transplantation. It is not known whether the risk of basal cell carcinoma (BCC) has reduced in line with this. What does this study add? Our study documents a progressive fall in the risk of SCC and BCC following solid organ transplantation over the last two decades. The SCC-to-BCC ratio was maintained, demonstrating that both are reducing equally. The trends observed in our study coincided with temporal changes in immunosuppressive protocols and the introduction of cancer prevention programmes, suggesting that these factors have positively impacted on the risk of keratinocyte carcinoma in this cohort.

Analysis of an electrical impedance spectroscopy system in short-term digital dermoscopy imaging of melanocytic lesions.

BACKGROUND: Electrical impedance spectroscopy (EIS) is a noninvasive diagnostic technique that measures tissue impedance. OBJECTIVES: To evaluate the effect of adding an EIS measurement at baseline to suspicious melanocytic lesions undergoing routine short-term sequential digital dermoscopy imaging (SDDI). METHODS: Patients presented with suspicious melanocytic lesions that were eligible for short-term SDDI (with no clear feature of melanoma on dermoscopy). EIS measurement was performed at the first visit following dermoscopic photography. Normally, an EIS score of ≥ 4 is considered positive; however, this protocol investigated a higher cut-off in combination with SDDI. When the EIS score was ≥ 7 the lesion was excised immediately owing to the high risk of melanoma. Lesions with a score < 7 were monitored with standard SDDI over a 3-month period. RESULTS: From a total of 160 lesions analysed, 128 of 154 benign lesions received an EIS score of 0-6, giving a specificity of the EIS method for the diagnosis of melanoma of 83·1% [95% confidence interval (CI) 76·3-88·7]. Five of the six melanomas found in this study had an EIS score ≥ 7, with a sensitivity for melanoma diagnosis of 83·3% (95% CI 35·9-99·6). When EIS 0-6 lesions were subsequently followed up with SDDI, one additional melanoma was detected (EIS = 6) giving a sensitivity for the diagnosis of melanoma overall of 100% (95% CI 54·1-100; six of six malignant melanomas excised) and a specificity of 69·5% (95% CI 61·5-76·6; 107 of 154 benign lesions not excised). CONCLUSIONS: If utilizing a protocol where an EIS score ≤ 3 requires no SDDI and ≥ 7 requires immediate excision, it reduced the need for SDDI by 46·9% (n = 75/160; 95% CI 39·0-54·9).

Renal dysfunction in patients taking fumaric acid esters - a retrospective cross-sectional study.

BACKGROUND: Fumaric acid esters (FAE) have been used for over 30 years in the management of psoriasis. There have been a number of case reports linking the use of FAE with nephrotoxicity, including acute renal injury and Fanconi syndrome. However, one large multicentre retrospective trial showed no evidence of renal dysfunction with FAE. OBJECTIVES/AIMS: The aim of this study was to determine the number of patients in our institution being treated with FAE who developed significant proteinuria or renal dysfunction. METHODS: This was a single-centre retrospective study assessing all patients on FAE who attended for follow-up during an 18-week period between February and June 2015. Demographics, comorbidities, duration and dose of treatment with FAE, proteinuria, renal function and other biochemical serum abnormalities were recorded. RESULTS: One hundred and twenty-seven patients were included in the study. Eighty-two patients had proteinuria detected at some stage during treatment with FAE, and 18 of these had persistent proteinuria (positive in at least three consecutive specimens, 12 weeks apart). Six patients (five female) developed proximal tubular dysfunction (PTD). The risk factors for the development of PTD appear to be lower bodyweight (P = 0.03), higher dose per weight (P = 0.03) and longer duration of treatment (P = 0.03). Renal dysfunction improved on discontinuation or dose reduction in FAE. CONCLUSION: Fumaric acid esters are frequently associated with transient or persistent proteinuria. Significant renal dysfunction is rare and usually reversible on dose reduction or discontinuation of FAE. This study highlights the importance of screening for proteinuria. Higher doses per weight of treatment and longer duration of FAE therapy are likely risk factors for PTD.

Dermoscopy and in vivo confocal microscopy are complementary techniques for diagnosis of difficult amelanotic and light-coloured skin lesions.

BACKGROUND: Amelanotic melanomas are often difficult to diagnose. OBJECTIVES: To find and test the best methods of diagnosis using dermoscopy and reflectance confocal microscopy (RCM) tools. METHODS: We selected consecutive, difficult-to-diagnose, light-coloured and amelanotic skin lesions from three centres (in Australia and Italy). Dermoscopy and RCM diagnostic utility were evaluated under blinded conditions utilizing 45 melanomas (16 in situ, 29 invasive), 68 naevi, 48 basal cell carcinomas (BCCs), 10 actinic keratoses, 10 squamous cell carcinomas (SCCs) and 13 other benign lesions. RESULTS: Sensitivity and specificity for melanoma with dermoscopy pattern analysis by two blinded observers and their 'confidence in diagnosis' were low. The amelanotic dermoscopy method had the highest sensitivity (83%) for a diagnosis of malignancy (melanoma, BCC or SCC), but specificity was only 18%. Multivariate analysis confirmed the utility of RCM features previously identified for the diagnosis of BCC and melanoma (highest odds ratio for melanoma: epidermal disarray, dark and/or round pagetoid cells). RCM sensitivity was 67% and 73% for melanoma and BCC diagnosis, respectively, and its specificity for nonmalignant lesion diagnosis was 56%. RCM reader confidence was higher than for dermoscopy; 84% of melanomas would have been biopsied and biopsy avoided in 47% of benign lesions. All melanomas misclassified by either dermoscopy or RCM were detected by the other tool. CONCLUSIONS: Dermoscopy and RCM represent complementary/synergistic methods for diagnosis of amelanotic/light-coloured skin lesions.

The Crohn's disease-associated polymorphism in ATG16L1 (rs2241880) reduces SHIP gene expression and activity in human subjects.

Crohn's disease (CD) is a polygenic immune-mediated disease characterized by gastrointestinal inflammation. Mice deficient in the hematopoietic-restricted SH2 domain-containing inositolpolyphosphate 5'-phosphatase (SHIP) develop spontaneous CD-like ileal inflammation. Intriguingly, SHIP mRNA is not upregulated in biopsies from patients with ileal CD despite immune cell infiltration, but SHIP's role in human CD remains unknown. We analyzed SHIP mRNA expression and activity in biopsies and peripheral blood mononuclear cells (PBMCs) from control and treatment-naive subjects with ileal CD, and demonstrated that SHIP mRNA and activity were lower in hematopoietic cells in ileal biopsies and PBMCs from subjects with CD. In all tissues from our patient cohort and in PBMCs from a second healthy control cohort, subjects homozygous for the autophagy-related 16-like protein (ATG16L1) CD-associated gene variant (rs2241880), had low SHIP mRNA expression and activity. SHIP protein expression increased during autophagy and SHIP upregulation was dependent on ATG16L1 and/or autophagy, as well as the ATG16L1 CD-associated gene variant. Finally, homozygosity for the ATG16L1 risk variant and low SHIP mRNA expression is inversely related to increased (LPS+ATP)-induced IL-1ß production by PBMCs in our cohorts and was regulated by increased transcription of ILIB. These data suggest a novel mechanism by which the ATG16L1 CD-associated gene variant may predispose people to develop intestinal inflammation.

Clinical practice guidelines for identification, screening and follow-up of individuals at high risk of primary cutaneous melanoma: a systematic review.

Understanding how individuals at high-risk of primary cutaneous melanoma are best identified, screened and followed up will help optimize melanoma prevention strategies and clinical management. We conducted a systematic review of international clinical practice guidelines and documented the quality of supporting evidence for recommendations for clinical management of individuals at high risk of melanoma. Guidelines published between January 2000 and July 2014 were identified from a systematic search of Medline, Embase and four guideline databases; 34 guidelines from 20 countries were included. High-risk characteristics that were consistently reported included many melanocytic naevi, dysplastic naevi, family history, large congenital naevi, and Fitzpatrick Type I and II skin types. Most guidelines identify risk factors and recommend that individuals at high risk of cutaneous melanoma be monitored, but only half of the guidelines provide recommendations for screening based on level of risk. There is disagreement in screening and follow-up recommendations for those with an increased risk of future melanoma. High-level evidence supports long-term screening of individuals at high risk and monitoring using dermoscopy. Evidence is low for defining screening intervals and duration of follow-up, and for skin self-examination, although education about skin self-examination is widely encouraged. Clinical practice guidelines would benefit from a dedicated section for identification, screening and follow-up of individuals at high risk of melanoma. Guidelines could be improved with clear definitions of multiple naevi, family history and frequency of follow-up. Research examining the benefits and costs of alternative management strategies for groups at high risk will enhance the quality of recommendations.

Surveillance for treatment failure of lentigo maligna with dermoscopy and in vivo confocal microscopy: new descriptors.

BACKGROUND: Nonsurgical treatment (radiotherapy, imiquimod) is increasingly employed for the management of lentigo maligna (LM). While the diagnosis of LM remains difficult, the detection of treatment failure is even more challenging. OBJECTIVES: To describe the sensitivity and specificity for the diagnosis of LM of individual features and methods using dermoscopy and in vivo reflectance confocal microscopy (RCM) to aid in the detection of treatment failure of LM following nonsurgical treatment. METHODS: A retrospective study of dermoscopy and RCM images (blinded to the correlation with pathology) in patients with biopsy-confirmed LM who were undergoing nonsurgical treatment in two referral institutions - one in Sydney, Australia, and the other in Barcelona, Spain. Ninety-eight patients were treated nonsurgically for LM during the period 2006-2012. Thirty-one patients had abnormal dermoscopy or RCM evaluation, and had a biopsy that identified LM recurrence in 15 patients and nonmelanoma diagnoses in 16 patients (one Bowen disease, 15 solar changes). RESULTS: The diagnosis of treatment failure was difficult with dermoscopy, with a sensitivity of 80% and specificity of 56%, even with the interpretation of an expert. The best criterion was asymmetric hyperpigmented follicular openings, but this was present in only 47% of treatment failure LM. Isolated, very fine brown dots ('dust' appearance) correlated highly with the diagnosis of treatment failure LM (73% sensitivity and 88% specificity) and with pagetoid cells seen with RCM. The LM score, comprising six criteria, had a specificity of 94% and sensitivity of 100%. CONCLUSIONS: These methods and descriptors should help to manage the diagnosis of treatment failure.

Melanoma survivors at high risk of developing new primary disease: a qualitative examination of the factors that contribute to patient satisfaction with clinical care.

BACKGROUND: Providing ongoing clinical care that adequately addresses patients' medical, psychosocial and information needs is challenging, particularly for patient groups at increased risk of developing life-threatening disease such as malignant melanoma. This study examined a model of clinical care developed by the High Risk Clinic (HRC) of the Sydney Melanoma Diagnostic Centre in relation to patient satisfaction. METHODS: Semi-structured telephone interviews were conducted and analyzed using the framework of Miles and Huberman, and themes were organized using the qualitative software package, QSR NVivo8. RESULTS: Twenty HRC patients participated in the study (nine men, 11 women; mean age 57.6 years, age range 34-74 years; response rate 91%). Satisfaction with clinical care at the HRC was high. Factors contributing to patient satisfaction included: rapid and regular access to physicians who were perceived by participants as experts, the development of confidence and trust in one's treating doctor, and a sense of being cared about and understood by one's healthcare team. Although one-third of the participants reported some inconveniences in attending the clinic, these were viewed as minor difficulties and not significant barriers to care. Formal psychological support was not sought or expected by participants, although many expressed long-standing melanoma-related fears and concerns. CONCLUSIONS: Accessible, expert medical attention, delivered in a patient-centered manner was integral to melanoma survivors' satisfaction with clinical management. Appropriate referrals to psychological support may further increase satisfaction with clinical care.

Dermoscopy of acral melanoma: a multicenter study on behalf of the international dermoscopy society.

BACKGROUND: Most studies on dermoscopy of acral lesions were conducted in Asian populations. In this study, we analyzed these features in a predominantly Caucasian population. OBJECTIVE: Estimate the prevalence of dermoscopic features in acral lesions, and assess their level of agreement between observers. METHODS: In this retrospective multicenter study, 167 acral lesions (66 melanomas) were evaluated for 13 dermoscopic patterns by 26 physicians, via a secured Internet platform. RESULTS: Parallel furrow pattern, bizarre pattern, and diffuse pigmentation with variable shades of brown had the highest prevalence. The agreement for lesion patterns between physicians was variable. Agreement was dependent on the level of diagnostic difficulty. CONCLUSION: Lesions with a diameter >1 cm were more likely to be melanoma. We found as well that a benign pattern can be seen in parts of melanomas. For this reason one should evaluate an acral lesion for the presence of malignant patterns first.

Changes observed in slow-growing melanomas during long-term dermoscopic monitoring.

BACKGROUND: Melanomas vary in growth rate from rapidly developing nodular melanomas to slow-growing melanomas (SGM) that hardly change over years. OBJECTIVES: To evaluate longitudinal changes in dermoscopic findings of SGM. METHODS: We retrospectively analysed a dermoscopic image dataset from 15 pigmented lesion clinics, of SGM that were followed sequentially by digital dermoscopy for at least 1 year. We evaluated baseline and follow-up images for changes in global pattern, organization, colours, structure and size. RESULTS: Our series consisted of 92 SGM. On follow-up, these melanomas developed the following dermoscopic findings: more homogeneous and less reticular global dermoscopic pattern; more frequent disorganization of pattern (baseline, 67% vs. follow-up, 79%); decreased prominence of light brown colour, increased prominence of dark brown colour, and increased frequency of the colours red, white, grey, blue and black (baseline: 29%, 3%, 18%, 6% and 33% vs. follow-up: 41%, 10%, 31%, 13% and 45%, respectively); decrease in prominence of dermoscopic structure of pigmented network, with a concomitant increase in prominence of structureless areas; and increased prominence or new appearance of melanoma-specific dermoscopic structures, including negative network, blue-white structures and blotches. The majority of lesions (75%) remained the same size or grew by < 2 mm in diameter. An increase in lesion size was associated with change in the total number of colours and structures (χ(2) = 14·3, P = 0·027) at follow-up. CONCLUSIONS: While their diameter changed minimally over time, most SGM became more disorganized, revealed loss of network in favour of structureless areas, and developed new colours.

Slow-growing melanoma: a dermoscopy follow-up study.

BACKGROUND: Recent evidence suggests that melanoma is a family of different tumours with varying abilities to grow and metastasize. Trends in melanoma epidemiology show a strong increase in the incidence of thin melanoma, with no corresponding increase in mortality or incidence of thick melanoma. We initially evaluated five cases and found that none had baseline features suggestive of melanoma; excision was performed based on slight changes visible only in side-by-side comparisons of dermoscopic images. OBJECTIVES: To assess the clinico-dermoscopic features and the growth patterns of melanomas that were excised after a follow-up of 1 year or more due to their inconspicuous features at the baseline consultation. METHODS: In a multicentre, retrospective study of histopathologically confirmed melanomas excised after follow-up, we analysed dermoscopic images obtained at the initial consultation and compared them with images obtained at the last follow-up consultation. Images were analysed and graded using standard algorithms and scored for changes in size, symmetrical or asymmetrical structural change, and development of new melanoma-specific criteria. An overall score reflecting the amount of change was calculated for each lesion. RESULTS: Our series consisted of 103 melanomas. After a median follow-up of 20 months, most lesions were still in situ or early invasive (median Breslow thickness of 0.48 mm), with only three lesions showing tumour thickness of 1 mm or more. The most frequent baseline characteristics were asymmetrical pigmentation (78.6% of lesions), reticular overall pattern (62.1%), and regression features (35.9%). Most melanomas (58.3%) showed minor to moderate changes over time, with < 2 mm size increase, with asymmetrical structural change, and without development of new melanoma-specific criteria. Major changes were visible only after a mean follow-up of 33 months. CONCLUSIONS: This study provides evidence for the existence of a subgroup of slow-growing melanomas, which may explain the increase in the incidence of thin melanoma, despite stable rates of thick melanoma and melanoma-associated mortality.