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Extramammary Paget's disease (EMPD) is a rare adenocarcinoma that arises in apocrine gland-bearing skin and is associated with increased risk of underlying or distant malignancies. The average time between EMPD and malignancies that preceded EMPD diagnosis was 5.5 ± 6.7 years, and an average of 3.3 ± 3.9 years for malignancies diagnosed after EMPD. Increased incidence of secondary malignancies, particularly of colorectal and genitourinary cancers, in EMPD patients should prompt clinicians to conduct age-appropriate and other relevant and frequent cancer screening. [Extracted from the article]

Incidence rates of melanoma and keratinocyte skin cancers have been on the rise worldwide, despite public health efforts to reduce their burden.1 Exposure to ultraviolet (UV) radiation remains the primary modifiable risk factor,1-3 and therefore reducing UV exposure continues to be the focus of public health education and campaigns. The incorporation of duration of sun exposure and skin phototype, which have been shown to play roles in the development of skin cancer, should be included in the recommendations.1,3 Labelling UVI <= 2 as having "no risk" could potentially be harmful to at-risk individuals. [Extracted from the article]

Background: Skin cancer prevention relies on effective sun safety practices. Previous studies have shown that LGBTQ+ individuals exhibit lower sunscreen use and higher tanning bed usage compared to their non-LGBTQ+ counterparts. This study is the first to assess skin cancer risk factors, sun-protective behaviors, and skin cancer concerns among LGBTQ+ individuals across Canada., Methods: A national survey study was conducted between July 2020 and March 2024 and included LGBTQ+ respondents aged ≥ 16 years who had completed the survey. Responses were summarized using frequency counts/percentages for categorical variables and means/standard deviations for continuous variables. Logistic regression models were used to calculate age- and gender-adjusted odds ratios for subgroup analyses., Results: Of the 700 LGBTQ+ participants included (59.3% women; median age 38 years), the majority had a Fitzpatrick skin phototype (FSP) I-III (76.4%). Concerningly, 60% reported >10 lifetime sunburns, 58% reported ≥1 blistering sunburn, 34% had used a tanning bed ≥1 time in their lifetime, and 69% reported having a tan in the last 12 months. Sunscreen was worn regularly by only half of the respondents, and half of the participants agreed or strongly agreed with "I look better and/or healthier with a tan". Additional comparisons are presented based on gender, FSP, education, and income., Conclusion: The findings of this study highlight the need for public health campaigns tailored to the LGBTQ+ community, emphasizing culturally sensitive sun safety education, particularly for LGBTQ+ men, individuals with FSP IV-VI, and those with lower education levels, to help reduce future skin cancer risk.

The rapidly increasing skin cancer rates in Canada are alarming, with current data estimating that 1/3 of Canadians will be affected in their lifetime. Thus, deeper understanding of high-risk sun exposure behaviors is needed to help counter this trend. Only limited action has been taken by federal/provincial governments to reduce skin cancer incidence. A cross-sectional survey study was conducted in Manitoba, with frequency counts, means, and percentages used to encapsulate responses. Age- and gender-adjusted odds ratios were calculated using logistic regression analyses. Our study identified worrying inadequacies in sun protective behaviors and attitudes, with the threat of such high-risk behaviors amplified by a lack of skin cancer awareness. Alarming elements were noted in participants' sun exposure history (>65% reported a history of sunburns, >50% previously used a tanning bed, and >75% recently tanned for pleasure), beliefs and attitudes (>50% believe that they look better/healthier with a tan, and >40% believe that having a base tan is protective against further sun damage), and sun protection efforts (sun protective clothing was used <60% of the time, sunscreen was used by <50%, and there was a lack of knowledge about sunscreen characteristics in ~30% of respondents), in addition to significant differences being established between demographic subgroups (based on gender, age, skin phototype, income, and education attained). This study provides worrisome insight onto the grim landscape of sun protective behaviors and attitudes in Manitoba, which will inevitably translate into higher skin cancer rates and should serve as a call to action to promote targeted public health messaging in this jurisdiction and beyond.

Introduction: The mortality-to-incidence ratio (MIR) can be used to approximate healthcare inequities and is helpful to understand/compare cancer survival between geographic regions/jurisdictions. We investigated cutaneous melanoma (CM) outcomes through MIR analysis in Canadian jurisdictions and census divisions (CDs) between 1992 and 2016., Methods: Data were obtained from the national databases from 1992 to 2016 for all Canadian jurisdictions, except Quebec. Age-standardized overall and median MIRs were calculated per province per year, while crude MIRs were calculated for CDs. Generalized linear regression models were conducted to study the effect of province and year on MIR, while a mixed effect regression model was used to determine how healthcare and socioeconomic factors affect MIR, while accounting for possible clustering effects (eg, year and province)., Results: We identified 106,015 CM cases and 20,570 CM deaths between 1992 and 2016. National MIR from 1992 to 2016 demonstrated a significant linear decrease ( P value < .0001). The national median MIR was 15.4 (ie, 0.154 × 100), whereby Manitoba (19.9), Ontario (19.5), Saskatchewan (18.5), British Columbia (16.1), and Newfoundland and Labrador (15.9) demonstrated higher MIRs than the Canadian average. CDs with the highest MIRs were commonly identified in the southern regions of provinces. No healthcare or socioeconomic factors were found to be significantly associated with higher MIR at the provincial level., Conclusion: MIRs have decreased at the national and provincial levels in recent decades, which is reassuring. Higher MIRs were noted in select rural CDs and in the Canadian territories, reinforcing the importance of proper dermatological care in all parts of the country., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Cutaneous melanoma (CM) is a significant contributor to skin cancer-related mortality globally and in Canada. Despite the well-established link between ultraviolet (UV) radiation exposure and skin cancer risk, there remains a gap in population-level interventions and persistent misconceptions about sun exposure and impact of environment on individual behavior., Objective: The current study provides an ecological analysis using latest available data (2011-2017) to define geographic/environmental contributors to the CM landscape in Canada., Methods: Utilizing Canadian Cancer Registry and Canadian Urban Environmental Health Research Consortium data, we analyzed 39,605 CM cases occurring in Canada from 2011 to 2017. Environmental data, including UV radiation, greenspace (normalized difference vegetation index), temperature, heat events, and precipitation was used to evaluate the effect of environment on CM incidence rates across Forward Sortation Area postal codes., Results: Forward Sortation Areas with increased CM incidence were associated with higher annual average temperature, snowfall, heat events, normalized difference vegetation index, and vitamin D-weighted UV exposure. Conversely, factors associated with decreased incidence included an increased annual highest temperature, rain precipitation, and a longer duration of heat events., Limitations: This study is subject to ecological bias and findings should be interpreted with caution., Conclusion: This study further substantiates associations between specific environmental factors and CM incidence., Competing Interests: None disclosed., (© 2024 by the American Academy of Dermatology, Inc. Published by Elsevier Inc.)

Globally, cutaneous melanoma (CM) incidence is increasing, with sun exposure identified as a key modifiable risk factor. The Atlantic provinces of Canada display varied CM incidence rates: New Brunswick aligns with the national average, while Nova Scotia and Prince Edward Island exceed it, and Newfoundland and Labrador fall below this benchmark. We investigated the relationship between sun exposure and CM in these provinces. Twenty-two focus groups encompassing 95 Atlantic Canada residents were conducted and transcribed. A thematic analysis was conducted in MAXQDA using the social-ecological model as a framework. Residents of high-CM incidence provinces demonstrated greater sun exposure awareness, consulting UV indices, and using sunscreen and sun-protective clothing. However, they received greater UV exposure due to warmer climates and outdoor work and cultural activities. Conversely, those in low-incidence provinces used sunscreen and sun-protective clothing less often, engaged in occupations and hobbies affording less sun exposure, and lived in cooler climates. Our data supports a possible "sunscreen paradox", whereby increased sunscreen use is correlated with augmented sun exposure, leading to a deceptive sense of security. Public health initiatives in Atlantic Canada promoting sun safety must address this paradox while integrating community-specific behaviors and norms in order to develop tailored campaigns.

Competing Interests: Conflicts of interest None disclosed.

Background: The incidence of cutaneous melanoma (CM) is increasing at an alarming rate in Canada and elsewhere around the world. Significant regional differences in CM incidence have been identified in Atlantic provinces. The goal of this study is to compare ultraviolet exposure, sun protective behaviours, level of worry and baseline CM knowledge in provinces with a high versus low incidence of CM as well, as between various demographic groups., Methods: A cross-sectional survey study was conducted in Atlantic provinces between July 2020 and August 2022. All participants aged ≥ 16 years with a completed survey were eligible. Survey responses were summarized using frequency counts, percentages, and means. Two-sided Z-tests for equality of proportions and logistic regression models were used to compare the survey results between geographic and demographic groups., Results: In total, 7861 participants were included (28.0% men; mean age 61.3 years; response rate 28%). Our results (gender- and age-adjusted odds ratio, 95% confidence interval) show that high-incidence provinces for CM (Prince Edward Island and Nova Scotia) had significantly more sunburns (OR 2.00, 1.72-2.31), total sun exposure (OR 2.05, 1.68-2.50), recreational sun exposure (OR 1.95, 1.61-2.35) and tans (OR 1.77, 1.53-2.05) than individuals in low-incidence provinces (Newfoundland and Labrador). However, individuals in high-incidence provinces displayed more protective behaviors: there were less tanning bed users (OR 0.82, 0.71-0.95), they checked their skin more frequently for new moles (OR 1.26, 1.06-1.51) and practiced more sun protection overall. Additional analyses are presented based on education, income, sexual orientation and gender., Discussion: These findings suggest that future efforts aimed at reducing the CM burden in Atlantic Canada should be tailored for target geographic and/or demographic groups., Limitations: the study participants are not representative of the population in Atlantic Canada due to recruitment strategies.

Background: Sex and gender have increasingly been recognized as significant risk factors for many diseases, including dermatological conditions. Historically, sex and gender have often been grouped together as a single risk factor in the scientific literature. However, both may have a distinct impact on disease incidence, prevalence, clinical presentation, severity, therapeutic response, and associated psychological distress., Objectives and Project Description: The mechanisms that underlie differences in skin diseases between males, females, men, and women remain largely unknown. The specific objectives of this review paper are:To highlight the biological differences between males and females (sex), as well as the sociocultural differences between men and women (gender) and how they impact the integumentary system.To perform a literature review to identify important sex- and gender-related epidemiological and clinical differences for various skin conditions belonging to a range of disease categories and to discuss possible biological and sociocultural factors that could explain the observed differences.To discuss dermatological skin conditions and gender-affirming treatments within the transgender community, a population of individuals who have a gender identity which is different than the gender identity they were assigned at birth., Future Impact: With the rising number of individuals that identify as non-binary or transgender within our increasingly diverse communities, it is imperative to recognize gender identity, gender, and sex as distinct entities. By doing so, clinicians will be able to better risk-stratify their patients and select treatments that are most aligned with their values. To our knowledge, very few studies have separated sex and gender as two distinct risk factors within the dermatology literature. Our article also has the potential to help guide future prevention strategies that are patient-tailored rather than using a universal approach.

Incidence rates of melanoma and keratinocyte skin cancers have been on the rise globally in recent decades. While there has been a select focus on personal sun protection awareness, to our knowledge, there is a paucity of legislation in place to help support citizens' efforts to protect themselves from the harmful effects of ultraviolet radiation (UVR). Given this, we conducted a comprehensive review of legislation and guidelines pertaining to a variety of sun protection-related topics in countries of the Group of Seven (G7), Australia and New Zealand. Australia was the only country to have banned tanning beds for individuals of all ages, while other select countries have instituted bans for minors. In workplace policy, there is very little recognition of the danger of occupational UVR exposure in outdoor workers, and thus very few protective measures are in place. With regard to sports and recreation, certain dermatological/professional associations have put forward recommendations, but no legislation was brought forward by government bodies outside of Australia and New Zealand. With regard to youth, while there are various guidelines and frameworks in place across several countries, adherence remains difficult in the absence of concrete legislation and standardization of procedures. Finally, only Australia and a few select jurisdictions in the United States have implemented sales tax exemptions for sunscreen products. In light of our findings, we have made several recommendations, which we anticipate will help reduce the rates of melanoma and keratinocyte cancers in years to come. However, minimizing UVR exposure is not without risk, and we, therefore, suggest the promotion of vitamin D supplementation in conjunction with sun protective practices to limit potential harm.

Sarcomas are a heterogeneous group of mesenchymal malignancies with various genetic and environmental risk factors. This study analyzed the epidemiology of sarcomas to gain insight into the incidence and mortality rates of these cancers in Canada, as well as to elucidate their potential environmental risk factors. Data for this study were obtained from le Registre Québécois du Cancer (LRQC) and from the Canadian Cancer Registry (CCR) for the period from 1992 to 2010. Mortality data were obtained from the Canadian Vital Statistics (CVS) database for the period from 1992 to 2010 using the International Classification of Diseases for Oncology, ICD-O-3, ICD-9, or ICD-10 codes, for all subtypes of sarcomas. We found that the overall sarcoma incidence in Canada decreased during the study period. However, there were select subtypes with increasing incidence. Peripherally located sarcomas were found to have lower mortality rates compared to axially located sarcomas, as expected. Clustering of Kaposi sarcoma cases in self-identified LGBTQ+ communities and in postal codes with a higher proportion of African-Canadian and Hispanic populations was observed. Forward Sortation Area (FSA) postal codes with a lower socioeconomic status also had higher Kaposi sarcoma incidence rates.

Actinic keratosis (AK) is among the most commonly diagnosed skin diseases with potentially life-threatening repercussions if left untreated. Usage of pharmacologic agents represents one of many therapeutic strategies that can be used to help manage these lesions. Ongoing research into these compounds continues to change our clinical understanding as to which agents most benefit particular patient populations. Indeed, factors such as past personal medical history, lesion location and tolerability of therapy only represent a few considerations that clinicians must account for when prescribing appropriate treatment. This review focuses on specific drugs used in either the prevention or treatment of AKs. Nicotinamide, acitretin and topical 5-fluorouracil (5-FU) continue to be used with fidelity in the chemoprevention of actinic keratosis, although some uncertainty persists in regard to which agents should be used in immunocompetent vs. immunodeficient/immunosuppressed patients. Topical 5-FU, including combination formulations with either calcipotriol or salicylic acid, as well as imiquimod, diclofenac and photodynamic light therapy are all accepted treatment strategies employed to target and eliminate AKs. Five percent of 5-FU is regarded as the most effective therapy in the condition, although the literature has conflictingly shown that lower concentrations of the drug might also be as effective. Topical diclofenac (3%) appears to be less efficacious than 5% 5-FU, 3.75-5% imiquimod and photodynamic light therapy despite its favorable side effect profile. Finally, traditional photodynamic light therapy, while painful, appears to be of higher efficacy in comparison to its more tolerable counterpart, daylight phototherapy.

Promotion in academia heavily relies on research productivity. The h-index is a standardized metric used to quantify research productivity at the individual level. We evaluated factors associated with h -index in dermatology across select Canadian academic centers with special focus on sex and academic rank. Medical academic centers throughout Canada with dermatology training programs were included. For each faculty member, we extracted the following data from public sources: sex, graduate degree, academic rank, years since the Fellow of the Royal College of Physicians and Surgeons of Canada (FRCPC) certification or equivalent, recent Canadian Institutes of Health Research (CIHR) funding and H-index (based on Scopus author profile). Log-linear univariate and multivariate regression analyses were performed to evaluate the association between h-index and these factors. An ordinal logistic regression was performed to explore sex differences in academic ranking. Our results showed that out of 300 faculty members across Canada, 155 were females (51.67%) and 145 were male (48.33%). H-index was available for 279 dermatologists. The average h-index was 8.35 (SD 11.53) and the median was 4.00 (1st quartile = 2.00, 3rd quartile = 10.00). Higher h-index was associated with more years since dermatology certification, successive academic rank, graduate degree and recent CIHR funding, but not with sex. In conclusion, h-index was not associated with sex when controlling for potential confounders. These results could reflect recent demographic changes in the field with an increase in newly appointed female dermatologists. Longitudinal assessment of academic productivity in dermatology is needed to assess the impact of continued efforts to promote equal opportunities in the field., Competing Interests: Conflict of interest Ivan Litvinov is the president of the Skin Research Group of Canada and research coordinator in the Division of Dermatology, McGill University. Other authors declare no competing interests.

Background/aims: Uveal melanoma is the most common type of non-cutaneous melanoma and the most common ocular malignancy in the adult population, especially affecting Caucasians (98% of cases). Despite its low incidence rate, we have noted increasing incidence trends in recent years., Methods: We analyzed uveal melanoma incidence data using the Canadian Cancer Registry (CCR) for 2011-2017 years. The data was examined using the International Classification of Diseases for Oncology, Third Edition, codes for all uveal melanoma subtypes. The data for 2011-2017 was then compared to previously published work by our research group for uveal melanoma incidence in Canada between 1992 and 2010 using the same methodology., Results: Between 2011 and 2017, 1,215 patients were diagnosed with uveal melanoma, 49% of whom were females. The percentage distribution of uveal melanoma between the sexes was similar between 1992-2010 and 2011-2017, whereby of the 2,215 diagnoses of uveal melanoma in 1992-2010, 47.9% were females. The change in the incidence rate for this cancer has doubled between 1992-2010 and 2011-2017, from 0.074 to 0.15 cases per million individuals per year. Our study documents that the Canadian 2011-2017 age-standardized incidence rate (ASIR) for uveal melanoma against the World Health Organization (WHO) 2000-2025 world population standard was 5.09 cases per million individuals per year (95% confidence interval, 4.73-5.44), as compared with the 1992-2010 rate of 3.34 cases per million individuals per year (95% confidence interval, CI 3.20 to 3.47)., Conclusion: This work demonstrates an ongoing, steady increase in uveal melanoma incidence in Canada in recent years., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Conte, Lagacé, Ghazawi, Cattelan, Nath, Dhillon, Nedjar, Rahme, Sasseville, Burnier and Litvinov.)

Retinoids are natural and synthetic vitamin A derivatives that are effective for the prevention and the treatment of non-melanoma skin cancers (NMSC). NMSCs constitute a heterogenous group of non-melanocyte-derived skin cancers that impose substantial burdens on patients and healthcare systems. They include entities such as basal cell carcinoma and cutaneous squamous cell carcinoma (collectively called keratinocyte carcinomas), cutaneous lymphomas and Kaposi's sarcoma among others. The retinoid signaling pathway plays influential roles in skin physiology and pathology. These compounds regulate diverse biological processes within the skin, including proliferation, differentiation, angiogenesis and immune regulation. Collectively, retinoids can suppress skin carcinogenesis. Both topical and systemic retinoids have been investigated in clinical trials as NMSC prophylactics and treatments. Desirable efficacy and tolerability in clinical trials have prompted health regulatory bodies to approve the use of retinoids for NMSC management. Acceptable off-label uses of these compounds as drugs for skin cancers are also described. This review is a comprehensive outline on the biochemistry of retinoids, their activities in the skin, their effects on cancer cells and their adoption in clinical practice.

Extracorporeal photopheresis (ECP) is an immunomodulatory therapy that has been used for over 35 years to treat numerous conditions. ECP was initially approved by the US FDA in 1988 for the treatment of Sézary syndrome, a leukemic form of cutaneous T-cell lymphoma (CTCL). Although CTCL remains the only FDA-approved indication, ECP has since been used off-label for numerous other conditions, including graft-versus-host disease (GvHD), systemic sclerosis, autoimmune bullous dermatoses, Crohn's disease, and prevention of solid organ transplant rejection. In Canada, ECP is mainly used to treat CTCL, acute and chronic GvHD, and in some instances systemic sclerosis. Herein, we review the current concepts regarding ECP mechanism of action, treatment considerations and protocols, and efficacy., Competing Interests: Elena Netchiporouk has received grants, research support from Novartis, Sanofi, Sun Pharma, AbbVie, Biersdorf, Leo Pharma, Eli Lilly; speaker fees/ honoraria from Bausch Health, Novartis, Sun Pharma, Eli Lilly, Sanofi Genzyme, AbbVie, Galderma, Novartis, Sanofi Genzyme, Sun Pharma, Bausch Health and Leo Pharma and consulting fees from Bausch Health, Novartis, Sun Pharma, Eli Lilly, Sanofi Genzyme, AbbVie, Galderma, Novartis, Sanofi Genzyme, Sun Pharma, Bausch Health and Leo Pharma. Irina Turchin served as advisory board member, consultant, speaker and/or investigator for AbbVie, Amgen, Arcutis, Aristea, Bausch Health, Boehringer Ingelheim, Celgene, Eli Lilly, Galderma, Incyte, Janssen, Kiniksa, Leo Pharma, Mallinckrodt, Novartis, Pfizer, Sanofi, UCB. Wayne Gulliver received grants/research support from AbbVie, Amgen, Eli Lilly, Novartis and Pfizer; honoraria for advisory boards/invited talks from AbbVie, Actelion, Amgen, Arylide, Bausch Health, Boehringer, Celgene, Cipher, Eli Lilly, Galderma, Janssen, Leo Pharma, Merck, Novartis, PeerVoice, Pfizer, Sanofi-Genzyme, Tribute, UCB, Valeant and clinical trial (study fees) from AbbVie, Asana Biosciences, Astellas, Boehringer-Ingelheim, Celgene, Corrona/National Psoriasis Foundation, Devonian, Eli Lilly, Galapagos, Galderma, Janssen, Leo Pharma, Novartis, Pfizer, Regeneron, UCB. Gizelle Popradi has received honoraria or speaker fees from Jazz Pharma, Seattle Genetics, Abbvie, Kite Gilead, Pfizer, Taiho, Servier, Novartis, Merck, Kyowa Kirin, Abbvie, Avir Pharma, Mallinckrodt. Robert Gniadecki reports carrying out clinical trials for Bausch Health, AbbVie and Janssen and has received honoraria as consultant and/or speaker from AbbVie, Bausch Health, Eli Lilly, Janssen, Mallincrodt, Novartis, Kyowa Kirin, Sun Pharma and Sanofi. Charles Lynde was a consultant, speaker, and advisory board member for Amgen, Pfizer, AbbVie, Janssen, Novartis, Mallincrodt, and Celgene, and was an investigator for Amgen, Pfizer, AbbVie, Janssen, Lilly, Novartis, and Celgene. Ivan V. Litvinov received research grant funding from Novartis, Merck, AbbVie and Bristol Myers Squibb and honoraria from Janssen, Bausch Health, Galderma, Novartis, Pfizer, Sun Pharma, Johnson & Johnson and Actelion. Topics included in this article were based on, but not limited to, broad discussions at an advisory board meeting, which was sponsored and funded by Mallinckrodt, Inc. Consultancy fees were paid to meeting participants (EN, IT, WG, JD, MK, RG, CL and IVL). All other authors declare no existing competing interests., (Copyright 2022 by SkinCareGuide.com Ltd. Skin Therapy Letter© is published 6 times annually by SkinCareGuide.com Ltd, 1003 - 1166 Alberni Street, Vancouver, British Columbia, Canada, V6E 3Z3. All rights reserved. Reproduction in whole or in part by any process is strictly forbidden without prior consent of the publisher in writing.)

Background: Cutaneous leishmaniasis is increasingly encountered in returned travellers and migrants to nonendemic countries. We sought to describe the clinical characteristics and treatment outcomes of cases of cutaneous leishmaniasis diagnosed at our reference centre over a 10-year period., Methods: This case series included all laboratory-confirmed cases of cutaneous leishmaniasis in travellers and migrants for whom complete clinical data were available, diagnosed between January 2008 and October 2018 at the J.D. MacLean Centre for Tropical Diseases in Montréal. We examined the number of cases each year. We used descriptive statistics to summarize variables (e.g., demographic characteristics, travel history, clinical presentation, diagnostic methods, treatments, adverse events) extracted from the patients' electronic medical records. The primary outcome for evaluating clinical response to treatment was defined as the complete re-epithelialization of the wound surface at 1 year., Results: We identified 48 patients who received diagnoses of cutaneous leishmaniasis in the 10-year study period, including 33 exposed in the Americas and 15 exposed in other regions (median age 43.5 [range 1-75] yr); 28 [58%] males). The annual number of cases increased from 9 in 2008/09 to 16 in 2017/18. The median time from onset to diagnosis was 89 (IQR 58-134) days. Liposomal amphotericin B was the most commonly used initial treatment (20 [53%] patients). Thirty-five patients completed their follow-up, and 11 had successful response to 1 course of liposomal amphotericin B. Adverse events (including acute kidney injury, increased pancreatic enzymes and fatigue) were reported in 6 (30%) patients. Clinical cure was achieved within 1 year for 32 (91%) of the 35 patients who completed follow-up., Interpretation: This study showed an increase in the number of cases of cutaneous leishmaniasis seen in our centre over the study period, likely because of increased travel and migration. This diagnosis should be considered in travellers and migrants with a chronic cutaneous lesion., Competing Interests: Competing interests: Momar Ndao reports funding from the McGill Interdisciplinary Initiative in Infection and Immunity. Cédric Yansouni reports funding from Fonds de recherche du Québec, consulting fees from Medicago, participation on an independent data monitoring committee for a phase 3 trial of a SARS-CoV-2 vaccine and a role as scientific advisor with the COVID-19 Immunity Task Force. Makeda Semret reports participation with data safety monitoring boards for SARS-CoV-2 vaccine studies and with the COVID-19 Immunity Task Force. Michael Libman reports funding from the Centers for Disease Control and Prevention, consulting fees for participation with an advisory board on education in travel medicine and a role as chair of the Committee to Advise on Tropical Medicine and Travel with the Public Health Agency of Canada. All competing interests are outside the submitted work. No other competing interests were declared., (© 2022 CMA Impact Inc. or its licensors.)

Background: Cutaneous melanoma (CM) is one of the most fatal types of skin cancer. Alarmingly, increases in incidence and mortality were noted globally for this malignancy, despite increase in understanding of melanoma pathogenesis and enhanced prevention efforts., Methods: Data was extracted for CM patients for provinces and territories (except Quebec) using two independent, population-based registries. Analysis was performed using both clinical and pathological characteristics: tumor morphologic classification, age, sex, anatomic site affected and place of residence. Mortality trends were assessed over a 7-year period. Results were compared to prior findings for 1992-2010., Results: During 2011-2017 39,610 patients were diagnosed with CM, with 5,890 reported deaths. National crude CM incidence was 20.75 (age-standardized incidence: 14.12) cases per 100,000 individuals per year. Females accounted for 45.8% of cases and 37.1% of deaths. While CM incidence rates continue to increase in both sexes, since 2013 the CM mortality is declining. We observed important differences across the provinces/territories, where Nova Scotia, Prince Edward Island, southern Ontario/British Columbia and certain coastal communities of New Brunswick demonstrated higher CM incidence and mortality rates. The observed incidence and mortality trends for 2011-2017 validate and extend earlier observations from 1992 to 2010 for CM., Conclusion: This population-based study highlights that while melanoma's incidence is increasing in Canada, mortality rates are for the first time decreasing since 2013. We detail regional distribution of this cancer highlighting communities in southern/coastal areas, as being most at risk as well as the latest trends of melanoma incidence by age, sex and anatomic site. In males, melanoma is more common on the head/trunk, while in females on the extremities. Notably, Acral Lentiginous Melanoma was the only CM subtype that was more common in females, which primarily affects hands and feet., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Conte, Ghazawi, Le, Nedjar, Alakel, Lagacé, Mukovozov, Cyr, Mourad, Miller, Claveau, Salopek, Netchiporouk, Gniadecki, Sasseville, Rahme and Litvinov.)

Background: Over 90% of skin cancers including cutaneous melanoma (CM) are related directly to sun exposure. Despite extensive knowledge on ultraviolet radiation's (UVR) detrimental impact, many still fail to implement sun protection/sun avoidance. Human behavior, attitudes, and cultural norms of individuals and communities heavily depend on the surrounding climate/environment. In many instances, the climate shapes the culture/norms of the society. Canada has vast geographic/environmental differences., Methods: In the current ecological study, we sought to examine the relationship between various geographic and environmental factors and the distribution of CM incidence by Forward Sortation Area (FSA) postal code across Canada. CM incidence data were extracted from the Canadian Cancer Registry, while environmental data were extracted from the Canadian Urban Environmental Health Research Consortium (greenspace, as measured by the normalized difference vegetation index; annual highest temperature; absolute number and average length of yearly heat events; annual total precipitation [rain and snow]; absolute number and average length of events with precipitation [rain and snow]; and summer UVR index). The above geographic/environmental data by FSA were correlated with the respective CM incidence employing negative binomial regression model., Results: Our analysis highlights that increases in annual average temperature, summer UVR, and greenspace were associated with higher expected incidence of CM cases, while higher number of annual heat events together with highest annual temperature and higher average number of annual rain events were associated with a decrease in CM incidence rate. This study also highlights regional variation in environmental CM risk factors in Canada., Conclusions: This national population-based study presents clinically relevant conclusions on weather/geographic variations associated with CM incidence in Canada and will help refine targeted CM prevention campaigns by understanding unique weather/geographic variations in high-risk regions., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Background: Gallbladder and biliary tract cancers are rare malignancies that carry a poor prognosis. Research on their epidemiologic trends is scarce., Methods: We performed a retrospective analysis of the data in Canada using population-based cancer registries from 1992 to 2010. The incidence and mortality of gallbladder and extrahepatic bile duct cancers were examined at the levels of provinces/territories, cities, and Forward Sortation Area (FSA) postal codes., Results: The incidence and mortality rates decreased over the study period. The average national incidence rate of gallbladder and biliary tract cancers was 30.92 cases per million individuals per year. Higher than average incidence rates were observed in Manitoba, Saskatchewan and Québec; there were contiguous regions with high incidence in Saskatchewan and Manitoba that suggest an area of putative case clustering. Higher incidence of gallbladder cancer was observed in women, whereas higher incidence of extrahepatic bile duct cancers was noted in men. Lower socioeconomic status and Hispanic race were found to be risk factors for gallbladder and biliary tract cancers., Conclusion: This is the first study to analyze the burden of gallbladder and biliary tract cancers in Canada. The geographic clustering trends present new avenues for research on environmental triggers., (Copyright © 2021 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Gastric cancer is the 5th most common malignancy worldwide, representing ~5-10% of all new cancer cases. Although its incidence is declining, it is estimated that 1 in 98 Canadians will develop gastric cancer in their lifetime. The epidemiology and distribution of gastric cancer throughout Canada, however, remains poorly understood. A retrospective analysis of demographic data across Canada between 1992 and 2010 was performed using 2 population-based cancer registries. The incidence of gastric cancer was examined at the levels of provinces, cities, and postal codes. In addition, 43,955 patients were diagnosed with gastric cancer in Canada between 1992 and 2010; 66% were male and the average age of diagnosis was 68.4 years. The age-adjusted incidence rate was 5.07 cases per 100,000 individuals per year. The incidence decreased over the study period by 30%. High incidence rates were identified in rural areas of Newfoundland and Labrador, New Brunswick, and Quebec. Our study found a significant association between gastric cancer incidence rates and lower socioeconomic status, as well as Hispanic ethnicity. This is the first study to provide a comprehensive analysis of the incidence of gastric carcinoma in Canada, identifying high-risk populations that may benefit from increased primary and secondary prevention.

Targeted therapy has been developed through an in-depth understanding of molecular pathways involved in the pathogenesis of melanoma. Approximately ~50% of patients with melanoma have tumors that harbor a mutation of the BRAF oncogene. Certain clinical features have been identified in BRAF -mutated melanomas (primary lesions located on the trunk, diagnosed in patients <50, visibly pigmented tumors and, at times, with ulceration or specific dermatoscopic features). While BRAF mutation testing is recommended for stage III-IV melanoma, guidelines differ in recommending mutation testing in stage II melanoma patients. To fully benefit from these treatment options and avoid delays in therapy initiation, advanced melanoma patients harboring a BRAF mutation must be identified accurately and quickly. To achieve this, clear definition and implementation of BRAF reflex testing criteria/methods in melanoma should be established so that patients with advanced melanoma can arrive to their first medical oncology appointment with a known biomarker status. Reflex testing has proven effective for a variety of cancers in selecting therapies and driving other medical decisions. We overview the pathophysiology, clinical presentation of BRAF -mutated melanoma, current guidelines, and present recommendations on BRAF mutation testing. We propose that reflex BRAF testing should be performed for every melanoma patient with stages ≥IIB.

In Canada, prostate cancer is the most common reportable malignancy in men. We assessed the temporal trends of prostate cancer to gain insight into the geographic incidence and mortality trends of this disease. Three independent population-based cancer registries were used to retrospectively analyze demographic data on Canadian men diagnosed with prostate cancer and men who died of prostate cancer between the years of 1992 and 2010. The incidence and mortality rates were calculated at the provincial, city, and forward sortation area (FSA) postal code levels by using population counts that were obtained from the Canadian Census of Population. The Canadian average incidence rate was 113.57 cases per 100,000 males. There has been an overall increasing trend in crude prostate cancer incidence between 1992 and 2010 with three peaks, in 1993, 2001, and 2007. However, age-adjusted incidence rates showed no significant increase over time. The national mortality rate was calculated to be 24.13 deaths per 100,000 males per year. A decrease was noted in crude and age-adjusted mortality rates between 1992 and 2010. Several provinces, cities, and FSAs had higher incidence/mortality rates than the national average. Several of the FSA postal codes with the highest incidence/mortality rates were adjacent to one another. Several Canadian regions of high incidence for prostate cancer have been identified through this study and temporal trends are consistent with those reported in the literature. These results will serve as a foundation for future studies that will seek to identify new regional risk factors and etiologic agents.

Positive identification of human remains is the very first step in anthropological analysis, and the task may be particularly difficult in the case of fragmented bones. Histomorphometry methods have been developed to discriminate human from nonhuman bones, based on differences in the size and shape of Haversian systems between the two groups. Those methods all focus on a very specific type of bone, section, and zone. Therefore, the objective of this study was to test the efficiency of four histomorphometric methods on a sample of fragmented bones. The sample is composed of 37 archaeological and fresh specimens, 25 nonhumans (Bos taurus, Equus caballus, Sus scrofa, Capreolus, Canis familiaris, Cervus elaphus, Ovis, and Capra) and 12 humans (Homo sapiens). Eight histomorphometric criteria were collected from all intact osteons visible on each fragment and then inserted into the corresponding discriminate function of each method. The results were compared with the real origin to establish rates of correct classification for each method. The methods of Martiniaková et al. (2006) and Crescimanno and Stout (2012) obtained very low percentages of good classification (32 % and 67 %). Those of Cattaneo et al. (1999) obtained 94 % correct classification, but only after a correction of the units of measurement for Haversian canal area in their formula. The methods of Dominguez and Crowder (2012) obtained an 86 % rate for well-classified specimens. Some of the methods tested here contain errors in the original publication that make them unusable in their current state. Plus, it seems that histomorphometric methods developed from specific areas are more difficult to apply to fragments. A reduced number of intact osteons analyzed may partially affect the reliability of the method by being unrepresentative of the entire microstructure. Therefore, this study demonstrates that one should be cautious with the use of histomorphometric methods to distinguish human and nonhuman fragmented bone until further research can refine these methods to achieve greater reliability., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Hypopigmented mycosis fungoides (HMF) is a form of cutaneous T-cell lymphoma (CTCL), a heterogeneous group of extranodal non-Hodgkin's lymphomas. HMF has a unique set of defining features that include light colored to achromic lesions, a predilection for darker skin phototypes, an early onset of disease, and predominance of CD8 + T-cells, among others. In the current review, we detail the known pathways of molecular pathogenesis for this lymphoma and posit that an active Th1/cytotoxic antitumor immune response in part explains why this variant is primarily seen in children/adolescents and young adults, who do not exhibit signs of immunosenescence. As a result of this potent cytotoxic response, HMF patients experience mostly favorable overall prognosis, while hypopigmentation may in fact represent a useful surrogate marker of cytotoxic immunity targeting the malignant cells. Understanding the molecular processes behind the specific features that define HMF may lead to improved diagnostic accuracy, personalized prognosis by risk stratification, and improved management of HMF. Moreover, improving our knowledge of HMF may aid our further understanding of other cutaneous lymphomas.

Background: Penile invasive squamous cell carcinoma (SCC) is a rare disease with several known risk factors. However, few studies have assessed its incidence, mortality, and temporal trends., Objective: Our objectives are to analyze the epidemiology of penile SCC in Canada and to examine patient distribution with this cancer across Canada in order to elucidate population risk factors., Methods: Three independent cancer registries were used to retrospectively analyze demographic data from Canadian men diagnosed with penile invasive SCC between 1992 and 2010. The Canadian Census of Population was used to calculate incidence and mortality rates at the province and Forward Sortation Area levels., Results: The overall age-adjusted incidence rate was 6.08 cases per million males. Four provinces with statistically significantly higher incidence rates were identified. The national crude incidence rates increased linearly between 1992 and 2010, whereas the age-adjusted incidence rates showed no significant increase during this time period. The overall age-adjusted mortality rate was 1.88 deaths per million males per year. The province of Saskatchewan had significantly higher mortality rates. There was no increase in crude or age-adjusted mortality rates between 1992 and 2010. There was a significant positive correlation between incidence rates and obesity, Caucasian ethnicity, and lower socioeconomic status., Conclusion: This study was able to establish geographic variation for this malignancy at the provincial level. Although there are many established risk factors for penile SCC, our results suggest that the increase in crude incidence rates observed is largely due to the aging population.

Background: Esophageal cancer can be subdivided into two main histological subtypes with significant variability in their etiology and epidemiology. The incidence of esophageal adenocarcinoma (AC) is increasing across the developed countries, whereas the incidence of esophageal squamous cell carcinoma (SCC) is declining. Several risk factors have been identified in the pathogenesis of each subtype, however, their epidemiologic characteristics and distribution throughout Canada remain poorly understood., Methods: We performed a retrospective analysis of demographic data across Canada from 1992 to 2010 using two independent population-based cancer registries. The incidence of esophageal cancer, for each subtype, was examined at the levels of provinces/territories, cities, and postal codes., Results: A total of 19 790 patients were diagnosed with esophageal cancer in Canada between 1992 and 2010; 74% were males. The average national incidence rate was 33.5 cases per million individuals per year. Incidence of esophageal AC increased over time, with notable high-incidence rates on the Vancouver Island, the coasts of the Great Lakes, and the coasts of the Northumberland Strait in the Maritimes. The overall incidence of esophageal SCC has decreased. However, high incidence of esophageal SCC was detected in the Vancouver city, rural eastern Québec, and in the Maritimes. We also report clustering for each subtype using postal codes, which sheds light onto new avenues of research for potential environmental etiologies., Conclusions: This study, for the first time, provides a detailed analysis on the burden of esophageal cancer in Canada, revealing important geographic clustering trends., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background/purpose: Breast cancer is the malignancy with the highest incidence rate excluding non-melanoma skin cancers, and the second leading cause of cancer-related deaths among Canadian women. Many modifiable risk factors have been linked to the pathogenesis of this disease. The purpose of this study is to analyze the epidemiology of breast cancer in Canada and to examine its geographic distribution to help identify new risk factors for this disease., Methods: Three independent population-based cancer registries were used to retrospectively analyze demographic data from Canadian women diagnosed with invasive breast cancer across all provinces and territories between 1992 and 2010. The incidence and mortality rates were assessed at the provincial, city, and forward sortation area (FSA) postal code levels., Results: The overall age-adjusted incidence rate was 114.4 cases per 100,000 females per year. Six provinces and several groups of FSAs had significantly higher incidence rates. There was a significant increase in incidence and decrease in mortality rates between 1992 and 2010. The overall mortality rate was 31.5 deaths per 100,000 females per year. However, three provinces had significantly higher mortality rates., Conclusion: By identifying high-incidence areas for breast cancer, our study will help identify patient populations that are at higher risk for this malignancy. It will also act as a foundation for future studies to establish novel risk factors for this disease.

Background: Multiple myeloma (MM) is a malignancy of mature plasma cells. Environmental risk factors identified for this malignancy, among others, include farming and exposure to pesticides., Methods: Using 3 independent population-based databases (the Canadian Cancer Registry, le Registre Québécois du Cancer, and Canadian Vital Statistics), this study analyzed patients' clinical characteristics and the incidence, mortality, and geographic distribution of MM cases in Canada during 1992-2015., Results: In total, ~32,065 patients were identified, and 53.7% were male. The mean age at the time of diagnosis was 70 ± 12.1 years. The average incidence rate in Canada was 54.29 cases per million individuals per year, and linear regression modeling showed a steady rise in the annual rate of 0.96 cases per million individuals per year. At the provincial level, Quebec and Ontario had significantly higher incidence rates than the rest of Canada. An analysis of individual municipalities and postal codes showed lower incidence rates in large metropolitan areas and in high-latitude regions of the country, whereas high incidence rates were observed in smaller municipalities and rural areas. Land use analysis demonstrated increased density of crop farms and agricultural industries in high-incidence areas. A comparison with the available data from 2011-2015 showed several consistent trends at provincial, municipal, and regional levels., Conclusions: These results provide a comprehensive analysis of the MM burden in Canada. Large metropolitan cities as well as high-latitude regions were associated with lower MM incidence. Higher incidence rates were noted in smaller cities and rural areas and were associated with increased density of agricultural facilities., (© 2019 American Cancer Society.)

Background: We recently reported a steady increase in the incidence and mortality of cutaneous malignant melanoma (CMM) in Canada during 1992-2010., Objectives: The objective of this article is to examine the distribution of Canadian CMM patients at the level of provinces, cities, and forward sortation area (FSA) postal codes., Methods: Using 3 Canadian population-based registries, we conducted an in-depth examination of the incidence and mortality trends for 72 565 Canadian CMM patients over the period 1992-2010., Results: We found that among 20- to 39-year-olds, the incidence of CMM in women (7.17 per 100 000 individuals) was significantly higher than in men (4.60 per 100 000 individuals per year). Women age 80 years and older had an incidence of CMM (58.46 cases per 100 000 women per year) more than 4 times greater than the national average (12.29 cases per 100 000 population per year) and a corresponding high mortality rate (20.18 deaths per 100 000 women per year), when compared with the Canadian melanoma mortality of 2.4 deaths per 100 000 per year. In other age groups men had higher incidence and corresponding melanoma mortality rates. We also studied CMM incidence by province, city, and FSA postal codes and identified several high-incidence communities that were located near the coast/waterfronts. In addition, plotting latitude measures for cities and FSAs vs CMM incidence rate confirmed the inverse relationship between geographical latitude and incidence of melanoma in Canada (slope = -0.22 ± 0.05)., Conclusions: This research may help develop sex-, age- and geographic region-specific recommendations to decrease the future burden of CMM in Canada.

Histomorphometric methods for age-at-death estimation constitute alternatives to macroscopic ones in the forensic context. However, all new methods must be tested on independent samples to justify their use and assure their accuracy. The main goal of this study was to test a new age-at-death method presented by Goliath et al. (2016) on a sample of 29 decalcified femur sections from individuals autopsied in the Institute of Legal Medicine of Montpellier, France. The formula proposed by the authors was not efficient to estimate the age-at-death in our sample, with only four out of 29 individuals well estimated. Despite this result, the same relationship between age and histomorphometric criteria was found, though at a lower intensity than what Goliath et al. previously found in their study. The use of a different bone preparation technique from Goliath et al. does not allow us to propose a definitive conclusion on the accuracy of this method., (Copyright © 2019 Elsevier B.V. All rights reserved.)

To assess radium ( 226 Ra) as a potential indicator of impact in well waters, we investigated its behavior under natural conditions using a case study approach. 226 Ra geochemistry was investigated in 67 private wells of southeastern New Brunswick, Canada, a region targeted for potential shale gas exploitation. Objectives were to i) establish 226 Ra baseline in groundwater; ii) characterize 226 Ra spatial distribution and temporal variability; iii) characterize 226 Ra partitioning between dissolved phase and particulate forms in well waters; and iv) understand the mechanisms controlling 226 Ra mobility under natural environmental settings. 226 Ra levels were generally low (median = 0.061 pg L -1 , or 2.2 mBq L -1 ), stable over time, and randomly distributed. A principal component analysis revealed that concentrations of 226 Ra were controlled by key water geochemistry factors: the highest levels were observed in waters with high hardness, and/or high concentrations of individual alkaline earth elements (i.e. Mg, Ca, Sr, Ba), high concentrations of Mn and Fe, and low pH. As for partitioning, 226 Ra was essentially observed in the dissolved phase (106 ± 19%) suggesting that the geochemical conditions of groundwater in the studied regions are prone to limit 226 Ra sorption, enhancing its mobility. Overall, this study provided comprehensive knowledge on 226 Ra background distribution at local and regional scales. Moreover, it provided a framework to establish 226 Ra baselines and determine which geochemical conditions to monitor in well waters in order to use this radionuclide as an indicator of environmental impact caused by anthropogenic activities (e.g. unconventional shale gas exploitation, uranium mining, or nuclear generating power plants)., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Radium (Ra) at environmental relevant levels in natural waters was determined by ICP-MS after an off-line pre-concentration procedure. The latter consisted of Ra selective elution from potential interfering elements (i.e. other alkaline earth cations: Ba 2+ , Sr 2+ , Ca 2+ , Mg 2+ ) on a series of two different ion exchange resins (AG50W-X8 and Sr-resin). The overall analytical method was optimized according to the instrumental performance, the volume of water sample loaded on resins, and the sample salinity. Longer acquisition time (up to 150 s) was required to ensure stable measurement of Ra by ICP-MS at ultra trace level (1.0pgL -1 ). For a synthetic groundwater spiked with Ra at 10.0pgL -1 , the analytical procedure demonstrated efficient separation of the analyte from its potential interfering elements and a complete recovery, independent of the sample volume tested from 10 up to 100mL. For synthetic seawater spiked at a level of 10.0pgL -1 of Ra, the total load of salts on the two resins should not exceed 0.35g in order to ensure a complete separation and recovery of Ra. The method was validated on natural waters (i.e. groundwater, freshwater and seawater samples) spiked with Ra at different levels (0.0, 0.5, 1.0 and 5.0pgL -1 ). Absolute Ra detection limits were determined at 0.020pgL -1 (0.73mBqL -1 ) and 0.12pgL -1 (4.4mBqL -1 ) respectively for 60.0mL of freshwater sample and for 10.0mL of seawater., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Primary graft failure, secondary to either host-vs.-graft reaction or delayed engraftment, and graft-vs.-host disease (GVHD) are among the most difficult clinical problems to manage in the field of allogeneic bone marrow transplantation (BMT). Early diagnosis of both conditions would greatly improve their outcome. Using fluorescence in situ hybridization (FISH) with an X- and Y-probe mixture, we sequentially monitored chimerism of neutrophils and lymphoid cells from day 1 to 100 in 28 consecutive recipients of sex-mismatched unmanipulated bone marrow grafts. The objective was to quantitatively assess the evolution of chimerism during this crucial time interval and to determine whether chimerism patterns would be predictive of engraftment and GVHD. In recipients with primary graft failure (n=7), the presence of donor-type neutrophils and NK cells as well as the predominance of donor-type T cells distinguished patients who responded to G-CSF (n=5) from nonresponders (n=2). Furthermore, the clearance of host CD3+CD56- cells during days 5-10 posttransplantation was significantly hastened in patients who subsequently developed acute (delta=80%) or chronic (delta=81%) GVHD compared with patients without GVHD (delta=17%). Thus, our data suggest that molecular monitoring of the fate of host/donor hematopoietic cells in the early posttransplantation period could be useful in differentiating patients with delayed engraftment from those with irreversible rejection and in predicting the occurrence of GVHD as soon as day 10. This investigational approach may provide an appropriate basis on which to select adequate treatment for primary graft failure and high-risk candidates that could benefit from novel preemptive therapies for GVHD.