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Xu J, Wang X, Liu W, Liu X, Li G. Analysis and comparison of the trends in burden of malignant cutaneous melanoma in East Asian countries and regions and worldwide from 1991 to 2021. Front Public Health 2025; 13:1487177. [PMID: 40371294 PMCID: PMC12075246 DOI: 10.3389/fpubh.2025.1487177] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2024] [Accepted: 04/14/2025] [Indexed: 05/16/2025] Open
Abstract
Objectives This study aims to comprehensively analyze temporal trends in the burden of malignant melanoma (MM) in East Asia, focusing on incidence, prevalence, mortality, and disability-adjusted life years (DALYs) from 1991 to 2021. It further seeks to compare these trends with the global burden of disease. Study design The study utilized data from the Global Burden of Disease (GBD) database to examine the disease burden of MM across East Asian countries and regions, as well as globally, over a 30-year period (1991-2021). Methods We assessed changes in the incidence, prevalence, mortality, and DALYs associated with MM in East Asia and globally using GBD database open-source data. To capture the underlying trends in the disease burden, we applied the Joinpoint regression model to calculate the average annual percentage change (AAPC) and corresponding 95% confidence intervals (95% CI). A detailed comparative analysis was conducted to explore differences in the burden of MM across East Asian regions and compared with global trends, with particular emphasis on age, sex, and temporal changes. Results The greatest increase in MM incidence in East Asia was observed in Korea, where the age-standardized incidence rate (ASIR) rose from 0.603 cases per 100,000 population (95% CI: 0.389-0.789) in 1991 to 1.896 cases per 100,000 (95% CI: 0.78-2.499) in 2021. Regarding prevalence, China exhibited the most significant increase in East Asia, with the age-standardized prevalence rate (ASPR) increasing from 0.699 (95% CI: 0.451-0.864) per 100,000 in 1991 to 4.157 (95% CI: 2.195-5.633) per 100,000 in 2021. The highest increases in MM mortality and DALYs were noted in Taiwan Province of China, where the age-standardized mortality rate (ASMR) increased from 0.36 (95% CI: 0.339-0.382) per 100,000 in 1991 to 0.414 (95% CI: 0.414) per 100,000 in 2021. Similarly, the age-standardized DALY rate (ASDR) in Taiwan rose from 10.375 (95% CI: 9.781-11.049) per 100,000 in 1991 to 11.647 (95% CI: 10.558-12.478) per 100,000 in 2021. Age and gender exhibited distinct patterns of influence on the MM burden: while ASIR generally increased with age, ASPR initially increased and later plateaued. Both ASMR and ASDR demonstrated a positive correlation with age. Additionally, male populations consistently exhibited higher morbidity and mortality rates than females. Conclusion Over the period from 1991 to 2021, there were significant variations in the incidence, prevalence, mortality, and DALY rates of MM across East Asian countries and regions, including China, Japan, South Korea, North Korea, and Taiwan. These disparities underscore the need for region-specific, proactive prevention strategies and targeted public health interventions to mitigate the growing burden of malignant melanoma in the region.
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Affiliation(s)
| | | | | | | | - Guangshuai Li
- The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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Zhang K, Zhang W, Lu H. Global Trends in the Incidence, Prevalence and Disability-Adjusted Life Years of Leprosy from 1990 to 2019: An Age-Period-Cohort Analysis Using the Global Burden of Disease Study 2019. Clin Cosmet Investig Dermatol 2025; 18:883-898. [PMID: 40225309 PMCID: PMC11994085 DOI: 10.2147/ccid.s508600] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2024] [Accepted: 03/19/2025] [Indexed: 04/15/2025]
Abstract
Background Leprosy is a neglected tropical disease, with approximately 200,000 new cases reported worldwide every year. Although there are numerous studies on the epidemiology of leprosy, the age, period, and cohort effects remain poorly understood. Objective We present an overview of trends in leprosy incidence, prevalence and disability-adjusted life years worldwide from 1990 to 2019 and associations with age, period, and birth cohort. Data for analysis were obtained from the Global Burden of Disease Study 2019. Methods We described incident case, prevalent case, age-standardised incidence, prevalence and disability-adjusted life years rates of leprosy from 1990 to 2019. Subsequently, we calculated overall annual percentage changes, annual percentage changes, and the relative risks of period and cohort using an age-period-cohort model. Results From 1990 to 2019, the global age-standardized incidence rate of leprosy decreased from 1.48 per 100,000 to 0.65 per 100,000. Additionally, countries with low Socio-Demographic Index (SDI) demonstrated higher age-standardised incidence, prevalence and disability-adjusted life years rate. The age-standardised incidence, prevalence and disability-adjusted life years rate were significantly higher in males compared to females. Furthermore, the impact of age on leprosy increased with age, peaking at 25-35 years, with the highest prevalence rates observed in the 35-40 age group. Notably, the peak age of leprosy onset increases with SDI. Both the period and cohort effects on leprosy incidence and prevalence showed decreasing trend in middle SDI, low-middle SDI and low SDI countries in recent 30 years and birth cohort later than 1905. However, unfavorable period and cohort effects were noted in high SDI regions. Conclusion Leprosy incidence, prevalence and disability-adjusted life years have significantly decreased globally, but remain high in areas with lower SDI. Developing regions should increase public awareness of leprosy risk factors, develop effective control policies to better manage and prevent the disease.
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Affiliation(s)
- Ke Zhang
- Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China
- Department of Dermatology, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China
| | - Wei Zhang
- Department of Dermatology, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China
| | - Hongguang Lu
- Department of Dermatology, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China
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Louie L, Wise J, Berl A, Shir-az O, Kravtsov V, Yakhini Z, Shalom A, Golberg A, Vitkin E. High-Throughput Metabolomic Profiling of Skin Lesions: Comparative Study of Cutaneous Squamous Cell Carcinoma, Basal Cell Carcinoma, and Normal Skin Via e-Biopsy Sampling. Cell Mol Bioeng 2025; 18:185-195. [PMID: 40290108 PMCID: PMC12018666 DOI: 10.1007/s12195-025-00846-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Accepted: 03/25/2025] [Indexed: 04/30/2025] Open
Abstract
Purpose Rising rates of cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC) make standard histopathology diagnostic methods a bottleneck. Using tissue molecular information for diagnostics offers a promising alternative. Faster specimen collection and high-throughput molecular identification can improve the processing of the increasing number of tumors. This study aims (i) to confirm the ability of e-biopsy technique to harvest metabolites, (ii) to obtain high-resolution metabolomic profiles of cSCC, BCC, and healthy skin tissues, and (iii) to perform a comparative analysis of the collected profiles. Methods Tumor specimens were collected with electroporation-based biopsy (e-biopsy), a minimally invasive sampling collection tool, from 13 tissue samples (cSCC, BCC, and healthy skin) from 12 patients. Ultra performance liquid chromatography and tandem mass spectrometry (UPLC-MS-MS) was used for molecular identification and quantification of resulting metabolomic profiles. Results Here we report measurements of 2325 small metabolites identified (301 with high confidence) in 13 tissue samples from 12 patients. Comparative analysis identified 34 significantly (p < 0.05) differentially expressed high-confidence metabolites. Generally, we observed a greater number of metabolites with higher expression, in cSCC and in BCC compared to healthy tissues, belonging to the subclass amino acids, peptides, and analogues. Conclusions These findings confirm the ability of e-biopsy technique to obtain high-resolution metabolomic profiles suitable to downstream bioinformatics analysis. This highlights the potential of e-biopsy coupled with UPLC-MS-MS for rapid, high-throughput metabolomic profiling in skin cancers and supports its utility as a promising diagnostic alternative to standard histopathology. Supplementary Information The online version contains supplementary material available at 10.1007/s12195-025-00846-1.
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Affiliation(s)
- Leetal Louie
- School of Mechanical Engineering, Tel Aviv University, Tel Aviv, Israel
| | - Julia Wise
- School of Mechanical Engineering, Tel Aviv University, Tel Aviv, Israel
| | - Ariel Berl
- Department of Plastic Surgery, Meir Medical Center, Kfar Sava, Israel
| | - Ofir Shir-az
- Department of Plastic Surgery, Meir Medical Center, Kfar Sava, Israel
| | | | - Zohar Yakhini
- Arazi School of Computer Science, Reichman University, Herzliya, Israel
- Department of Computer Science, Technion - Israel Institute of Technology, Haifa, Israel
| | - Avshalom Shalom
- Department of Plastic Surgery, Meir Medical Center, Kfar Sava, Israel
| | - Alexander Golberg
- School of Mechanical Engineering, Tel Aviv University, Tel Aviv, Israel
| | - Edward Vitkin
- School of Mechanical Engineering, Tel Aviv University, Tel Aviv, Israel
- Arazi School of Computer Science, Reichman University, Herzliya, Israel
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da Silva Carvalho AC, de Magalhães Ledsham Lopes C, Lobo AR, de Assis IA, de Medeiros HL, Drummond-Lage AP. Impact of the COVID-19 Pandemic on the Diagnosis and Treatment of Cutaneous Melanoma in a Public Health Service in Brazil. THE JOURNAL OF CLINICAL AND AESTHETIC DERMATOLOGY 2025; 18:E61-E65. [PMID: 40256343 PMCID: PMC12007661] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 04/22/2025]
Abstract
Objective The authors sought to evaluate the impact of the COVID-19 pandemic on the incidence, tumor thickness, and time between diagnosis and first treatment of cutaneous melanoma patients. Methods A retrospective observational study was conducted based on the analysis of electronic medical records of patients treated at a reference service in Cutaneous Oncology within the scope of the Unified Health System in Belo Horizonte, Brazil. The population was evaluated according to the date of diagnosis and was classified into three periods: 1) pre-pandemic period (January 2019 to March 2020), 2) pandemic period 1 (April 2020 to June 2021), and 3) pandemic period 2 (July 2021 to September 2022). Sociodemographic characteristics of the study population, tumor characteristics, and the time interval between diagnosis and first treatment were evaluated. Results Seventy-six patients were evaluated, 25 (32.89%) diagnosed in the pre-pandemic period, 22 (28.94%) in pandemic period 1, and 29 (38.15%) in pandemic period 2. No significant differences were observed between the sociodemographic characteristics of the population, tumor thickness, and the presence of ulceration in the three periods analyzed. There was also no delay between diagnosis and the first treatment during the pandemic. Limitations The size of the population, and the use of retrospective data extracted from medical records, without a systematized record of information. Conclusion The COVID-19 pandemic did not impact the incidence, thickness of melanomas, or the time between diagnosis and first treatment. This study demonstrated the importance of adapting the routine of health services and adapting the flow of oncology care in times of health crisis.
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Affiliation(s)
- Ana Carolina da Silva Carvalho
- Drs. da Silva Carvalho, de Magalhães Ledsham Lopes, and Drummond-Lage are with Programa de Pós-Graduação em Ciências da Saúde, Faculdade Ciências Médicas de Minas Gerais – FCM-MG in Belo Horizonte, MG, Brazil
| | - Carolina de Magalhães Ledsham Lopes
- Drs. da Silva Carvalho, de Magalhães Ledsham Lopes, and Drummond-Lage are with Programa de Pós-Graduação em Ciências da Saúde, Faculdade Ciências Médicas de Minas Gerais – FCM-MG in Belo Horizonte, MG, Brazil
| | - Amanda Ribeiro Lobo
- Mses. Lobo, de Assis, and de Medeiros are with Faculdade Ciências Médicas de Minas Gerais – FCM-MG in Belo Horizonte, MG, Brazil
| | - Isabela Almeida de Assis
- Mses. Lobo, de Assis, and de Medeiros are with Faculdade Ciências Médicas de Minas Gerais – FCM-MG in Belo Horizonte, MG, Brazil
| | - Helena Lourenço de Medeiros
- Mses. Lobo, de Assis, and de Medeiros are with Faculdade Ciências Médicas de Minas Gerais – FCM-MG in Belo Horizonte, MG, Brazil
| | - Ana Paula Drummond-Lage
- Drs. da Silva Carvalho, de Magalhães Ledsham Lopes, and Drummond-Lage are with Programa de Pós-Graduação em Ciências da Saúde, Faculdade Ciências Médicas de Minas Gerais – FCM-MG in Belo Horizonte, MG, Brazil
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Stawarz K, Galazka A, Misiak-Galazka M, Durzynska M, Gorzelnik A, Bienkowska-Pluta K, Korzon J, Kissin F, Zwolinski J. Advances in Skin Ultrasonography for Malignant and Benign Tumors of the Head and Neck: Current Insights and Future Directions. J Clin Med 2025; 14:2298. [PMID: 40217748 PMCID: PMC11989985 DOI: 10.3390/jcm14072298] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2025] [Revised: 03/14/2025] [Accepted: 03/24/2025] [Indexed: 04/14/2025] Open
Abstract
Ultrasound imaging has become an indispensable diagnostic tool across various medical fields. In recent years, there has been growing interest in the use of ultrasonography for the evaluation of skin lesions. However, scientific reports detailing the precise role of ultrasound in determining the morphology of malignant skin tumors still remain limited. Malignant skin lesions, particularly in the head and neck region-their most common location-pose significant challenges due to the complex anatomy of these areas. The primary treatment for non-melanoma skin cancers, including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), is surgical excision. Mohs micrographic surgery is considered the gold standard due to its tissue-sparing approach and high cure rates. However, it is a time-consuming and resource-intensive procedure that is not always widely accessible. In contrast, standard surgical excision, while more widely available, often results in incomplete tumor removal, necessitating subsequent surgical radicalization or the use of adjuvant therapies. Routine ultrasound evaluation of both benign and malignant skin lesions could enhance early detection and facilitate timely treatment. However, the current body of evidence for the usage of skin ultrasound in presurgical evaluation is poor and lacks standardization. Given these challenges, in this review, we aim to highlight the potential value of preoperative skin ultrasonography in accurately assessing benign and malignant skin lesion dimensions and morphology.
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Affiliation(s)
- Katarzyna Stawarz
- Head and Neck Cancer Department, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warszawa, Poland
| | - Adam Galazka
- Head and Neck Cancer Department, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warszawa, Poland
| | - Magdalena Misiak-Galazka
- Department of Pathology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warszawa, Poland
| | - Monika Durzynska
- Department of Pathology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warszawa, Poland
| | - Anna Gorzelnik
- Head and Neck Cancer Department, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warszawa, Poland
| | - Karolina Bienkowska-Pluta
- Head and Neck Cancer Department, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warszawa, Poland
| | - Jacek Korzon
- Head and Neck Cancer Department, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warszawa, Poland
| | - Filip Kissin
- Head and Neck Cancer Department, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warszawa, Poland
| | - Jakub Zwolinski
- Head and Neck Cancer Department, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warszawa, Poland
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Li J, Zeng J, Yang Y, Huang B. Trend of skin cancer mortality and years of life lost in China from 2013 to 2021. Front Public Health 2025; 13:1522790. [PMID: 40013033 PMCID: PMC11861555 DOI: 10.3389/fpubh.2025.1522790] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Accepted: 01/28/2025] [Indexed: 02/28/2025] Open
Abstract
Background The mortality rates of skin cancer in Chinese population are increasing. However, research on skin cancer trends in China is limited. This study aimed to estimate the mortality trends of skin cancer in China within 2013-2021. Methods A retrospective analysis of skin cancer deaths within 2013-2021 was performed using the China death cause surveillance dataset compiled by the National Health Commission Statistics Information Center and the China Center for Disease Control and Prevention Chronic Non-Communicable Diseases Prevention and Control Center. The mortality rates of skin cancer were stratified by gender, age group, and area (urban or rural). Results From 2013 to 2021 in China, the crude mortality rate (CMR) of skin cancer increased, and the age-standardized mortality rate (ASMR), and age-standardized years of life lost (YLL) rate decreased. The ASMR and age-standardized YLL rate were 0.85/100,000 and 18.95/100,000 in 2013, respectively, and decreased to 0.75/100,000 and 16.84/100,000, respectively, in 2021. From 2013 to 2021, the CMR, ASMR, and age-standardized YLL rate of skin cancer were higher in males than in females and higher in rural areas rather than in urban ones. In terms of the highest age-specific mortality rate, it appeared in the age group of over 85 years old. Conclusion The burden of skin cancer remained heavily from 2013 to 2021 in China. Especially males, older adult, and rural residents had higher mortality. Thus, effective measures and strategies should be taken to reduce the incidence and mortality of skin cancer.
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Affiliation(s)
- Jingyi Li
- Department of Dermatology, Huizhou First Hospital, Huizhou, China
| | - Jiaqi Zeng
- Department of Dermatology, Zhuhai People's Hospital (Zhuhai Clinical Medical College of Jinan University), Zhuhai, China
| | - Yuanchao Yang
- Department of Dermatology, Huizhou First Hospital, Huizhou, China
| | - Biran Huang
- Department of Dermatology, Huizhou First Hospital, Huizhou, China
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Liu C, Liu X, Cao P, Li X, Xin H, Zhu S. Global, regional, national prevalence, mortality, and disability-adjusted life-years of cutaneous squamous cell carcinoma and trend analysis from 1990 to 2021 and prediction to 2045. Front Oncol 2025; 15:1523169. [PMID: 39980558 PMCID: PMC11839636 DOI: 10.3389/fonc.2025.1523169] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Accepted: 01/20/2025] [Indexed: 02/22/2025] Open
Abstract
Background A serious worldwide health concern is cutaneous squamous cell carcinoma (cSCC). For the purpose of creating focused strategies, it is essential to comprehend geographical variations in cSCC prevalence and trends. Methods This study utilized data from the 2021 Global Burden of Diseases (GBD) survey to analyze cSCC across 204 countries and territories. We assessed the age-standardized prevalence rate (ASPR), mortality rate (ASMR), disability-adjusted life years (ASDR), and estimated annual percentage changes (EAPCs), with trends stratified by region, country, age, sex, and Sociodemographic Index (SDI). To evaluate disparities in cSCC burden, we combined the SDI with the inequality slope and concentration indices for an international health inequality analysis. Decomposition analysis assessed the effects of population growth, aging, and epidemiological trends on disease burden, while frontier analysis linked cSCC outcomes with socio-demographic development. A Bayesian Age-Period-Cohort (BAPC) model projected future prevalence, mortality, and DALYs, identifying key drivers of cSCC burden. Results In 2021, there were 2,275,834 cases of cSCC globally, reflecting a 345% increase since 1990. During this period, the ASPR rose from 14.69 to 26.85 per 100,000, while the ASMR increased slightly from 0.67 to 0.69 per 100,000. Disability-adjusted life years (DALYs) rose from 544,973 to 1,210,874. Among socio-demographic regions, the high SDI region had the highest ASPR, while the middle SDI region exhibited the highest ASMR and ASDR. Decomposition analysis identified population growth and demographic aging as key drivers of the rising ASMR. Countries like Georgia showed significant disparities in frontier analysis, indicating potential for better cSCC management. Health inequality analysis confirmed that the burden was concentrated in nations with higher SDI. By 2045, the global ASPR is projected to reach 64.66, with the ASMR and ASDR expected to decrease to 1.02 and 20.63 per 100,000, respectively. Conclusion Over the last three decades, the global burden of cSCC has increased significantly. While mortality rates and DALYs are expected to decline over the next twenty years, the prevalence of cSCC is projected to remain high. This highlights the urgent need to reevaluate preventive efforts aimed at reducing morbidity, particularly in areas with substantial populations over the age of 95.
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Affiliation(s)
- Chengling Liu
- Center of Burns and Plastic Surgery and Dermatology, The 924th Hospital of Joint Logistics Support Force of the Chinese People's Liberation Army (PLA), Guilin, China
| | - Xingchen Liu
- Department of Pathology, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Pengjuan Cao
- Department of Endocrinology and Traditional Chinese Medicine, The 924th Hospital of Joint Logistics Support Force of the Chinese People's Liberation Army (PLA), Guilin, China
| | - Xin Li
- Center of Burns and Plastic Surgery and Dermatology, The 924th Hospital of Joint Logistics Support Force of the Chinese People's Liberation Army (PLA), Guilin, China
| | - Haiming Xin
- Center of Burns and Plastic Surgery and Dermatology, The 924th Hospital of Joint Logistics Support Force of the Chinese People's Liberation Army (PLA), Guilin, China
| | - Sailin Zhu
- Center of Burns and Plastic Surgery and Dermatology, The 924th Hospital of Joint Logistics Support Force of the Chinese People's Liberation Army (PLA), Guilin, China
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Eigentler T, Thomas I, Samoylenko I, Erdmann M, Heinzerling L, Ochsenreither S, Krauss J, Oberoi A, Robert C, Lebbe C, Martin-Liberal J, Koch L, Richtig E, Terheyden P, Weishaupt C, Mohr P, Semiletova Y, Perez CL, Brossart P, Bauernfeind FG, Fluck M, Poltoratskiy A, Sekacheva M, Soria A, Schmitt-Bormann B, Gonzalez M, Heß J, Wengenmayer P, Seibel T, Koch SD, Quintini G, Codó P, Falk M, Schönborn-Kellenberger O, Gnad-Vogt U. Phase I study of intratumoral administration of CV8102 in patients with advanced melanoma, squamous cell carcinoma of the skin, squamous cell carcinoma of the head and neck, or adenoid cystic carcinoma. J Immunother Cancer 2025; 13:e009352. [PMID: 39904560 PMCID: PMC11795518 DOI: 10.1136/jitc-2024-009352] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Accepted: 11/24/2024] [Indexed: 02/06/2025] Open
Abstract
BACKGROUND CV8102, a toll-like receptor 7/8 and RIG I agonist, has demonstrated antitumor immune responses in preclinical studies. We investigated intratumoral (IT) administration of CV8102 in patients with anti-programmed cell death protein-1 (PD-1) therapy-naïve or anti-PD-1 therapy-refractory cutaneous melanoma (cMEL) and in patients with advanced cutaneous squamous cell carcinoma, head and neck squamous cell carcinoma and adenoid cystic carcinoma. METHODS This open-label, cohort-based, phase I dose escalation study aimed to establish the maximum tolerated dose (MTD), recommended dose (RD), safety and preliminary efficacy of CV8102 as monotherapy or in combination with a PD-1 inhibitor. The preliminary efficacy of the RD was assessed in patients with cMEL in the expansion cohorts. RESULTS Between September 2017 and October 2022, 98 patients were enrolled in monotherapy and combination therapy dose escalation and dose expansion cohorts. Two patients in the CV8102 monotherapy dose escalation cohort experienced relevant toxicities at the 900 µg dose level. One patient had Grade 3 aspartate transaminase/alanine aminotransferase elevation which met dose-limiting toxicity (DLT) criteria. Another patient experienced Grade 3 immune-mediated pneumonitis. No DLTs occurred in the combination therapy dose escalation cohort. The MTD was not formally reached and the RD for expansion was 600 µg. Common treatment-emergent adverse events were fever (57%), chills (37%) and fatigue (25%). In the dose escalation part, objective responses occurred in 3/33 patients treated with CV8102 as monotherapy and in 2/25 patients treated with CV8102 plus a PD-1 inhibitor. In the expansion cohorts in patients with anti-PD-1 therapy-refractory melanoma, 0/10 patients treated with CV8102 as monotherapy and 5/30 patients (17%) treated in combination with a PD-1 inhibitor experienced objective responses. CONCLUSIONS IT CV8102 was generally well tolerated with preliminary signs of efficacy as monotherapy and in combination with a PD-1 inhibitor. TRIAL REGISTRATION NUMBER NCT03291002.
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Affiliation(s)
- Thomas Eigentler
- Department of Dermatology, Venereology and Allergology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Berlin, Germany
| | - Ioannis Thomas
- Faculty of Medicine, University of Tübingen, Tubingen, Germany
| | - Igor Samoylenko
- Oncodermatology and surgical immunology unit, Blokhin Russian Cancer Research Center, Ministry of Health of Russia, Moscow, Russian Federation
| | - Michael Erdmann
- Department of Dermatology, Uniklinikum Erlangen, Comprehensive Cancer Center Erlangen - European Metropolitan Area of Nürnberg (CCC ER-EMN), Friedrich-Alexander-Universität (FAU), Erlangen, Germany
| | - Lucie Heinzerling
- Department of Dermatology & Allergy, LMU University Hospital, LMU Munich, München, Germany
- University Hospital Erlangen, Erlangen, Bayern, Germany
| | - Sebastian Ochsenreither
- Charité Comprehensive Cancer Center, Charité - Universitätsmedizin Berlin, Berlin, Germany
- Department of Hematology, Oncology and Tumor Immunology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Germany
| | - Jürgen Krauss
- National Center for Tumor Diseases, Heidelberg, Germany
| | - Arjun Oberoi
- Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology, Barcelona, Spain
| | - Caroline Robert
- Department of Oncology, Institut Gustave Roussy and Université Paris Saclay, Villejuif, France
| | - Celeste Lebbe
- Université Paris Cite, Dermato-Oncology and CIC AP-HP Hôpital Saint Louis and Cancer Institute APHP, Nord-Université Paris Cite, INSERM U976, Université Paris Cité, Paris, France
| | - Juan Martin-Liberal
- Medical Oncology Department, Catalan Institute of Oncology (ICO), Catalan Institute of Oncology, 08908 Barcelona, Spain
| | - Lukas Koch
- Department of Dermatology, Medical University of Graz, Graz, Austria
| | - Erika Richtig
- Department of Dematology, Medical University of Graz, Graz, Austria
| | - Patrick Terheyden
- Department of Dermatology, University of Lübeck, Lubeck, Schleswig-Holstein, Germany
| | - Carsten Weishaupt
- Department of Dermatology, Skin Cancer Center, University Clinic Münster, Munster, Germany
| | - Peter Mohr
- Department of Dermatology, Elbe Hospital, Buxtehude, Niedersachsen, Germany
| | - Yulia Semiletova
- St Petersburg State University Hospital, St Petersburg, Russian Federation
| | - Casilda Llacer Perez
- Medical Oncology Intercenter Unit, Regional and Virgen de la Victoria University Hospitals, IBIMA, Malaga, Spain
| | - Peter Brossart
- Department of Oncology, Hematology. Cell and Immunotherapies, University Hospital Bonn, Bonn, Nordrhein-Westfalen, Germany
| | - Franz Georg Bauernfeind
- Department of Oncology, Hematology. Cell and Immunotherapies, University Hospital Bonn, Bonn, Nordrhein-Westfalen, Germany
| | - Michael Fluck
- Department of Oncology Hornheide, Fachklinik Hornheide, Münster, Germany
| | - Artem Poltoratskiy
- Petrov Research Institute of Oncology, St Petersburg, Russian Federation
| | - Marina Sekacheva
- Institute for Personalized Oncology of the World-Class Research Center "Digital Biodesign and Personalized Healthcare", Schenenov University, Moscow, Russian Federation
| | - Ainara Soria
- Department of Medical Oncology, Hospital Universitario Ramón y Cajal, Madrid, Madrid, Spain
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Niforou A, Lagiou PD, Geller AC, Dessypris N, Stratigos AJ. Trends in Breslow thickness of nodular and superficial spreading melanoma subtypes and associated factors: a twelve-year analysis from a tertiary referral center in Greece. Ital J Dermatol Venerol 2025; 160:20-28. [PMID: 39841139 DOI: 10.23736/s2784-8671.24.08129-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2025]
Abstract
BACKGROUND Primary tumor thickness is important for prognosis of melanoma patients. To enhance prevention and quantify the true burden of melanoma, better understanding of thickness patterns and associated characteristics is crucial. Previous studies have been limited to report trends and address risk factors of thickness in specific melanoma subtypes in the Greek population. We investigated associations between epidemiological characteristics and thickness for the two most common melanoma subtypes and the trends in thickness over a twelve-year period. METHODS A retrospective study of 1201 patients with histologically confirmed primary nodular and superficial spreading melanoma (SSM) diagnosed from 2010 to 2021 in "Andreas Sygros" Hospital of Cutaneous and Venereal diseases was conducted. Multiple regression was performed to examine the association of variables of interest with melanoma thickness. RESULTS SSM thickness significantly increased by 2% per year (percent of change: 2.0, 95% CI: 0.2, 3.7) from 2010 to 2021, while a similar tendency for nodular melanoma (NM) thickness was indicated. Age at diagnosis was demonstrated to be a predictor of thickness for both subtypes. When considering all confounders, overall sun exposure was inversely associated with SSM thickness (PC: -6.2, 95% CI: -12.4, 0.5) and a similar association was indicated for NM (PC: -9.3, 95%CI: -21.1, 4.2). CONCLUSIONS These results indicate an upward trend of SSM thickness and the associations of age at diagnosis and overall exposure to UV with thickness of both subtypes. Future research is needed to identify additional characteristics and explain differences among all melanoma types.
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Affiliation(s)
- Aikaterini Niforou
- 1st Department of Dermatology-Venereology, Andreas Sygros Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, Greece -
- Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece -
| | - Pagona D Lagiou
- Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Alan C Geller
- Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Nick Dessypris
- Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Alexander J Stratigos
- 1st Department of Dermatology-Venereology, Andreas Sygros Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, Greece
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Jung JM, Kim DH, Kim YJ, Moon IJ, Lee WJ, Chang SE, Lee MW, Won CH. Risk of second primary malignancies among survivors of cutaneous melanoma: A nationwide population-based study in the Republic of Korea. Sci Rep 2025; 15:3541. [PMID: 39875452 PMCID: PMC11775261 DOI: 10.1038/s41598-025-87838-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Accepted: 01/22/2025] [Indexed: 01/30/2025] Open
Abstract
There is limited data on the risk of second primary malignancies (SPMs) in Asian melanoma survivors. This study aimed to identify the risk of SPMs in Asian melanoma survivors. Standardized incidence ratios (SIRs) were calculated for overall and specific SPMs. The risk factor for overall SPM development was analyzed using a multivariable Cox regression model. A total of 10,070 patients with melanoma were included in the study. Melanoma survivors exhibited an increased risk of overall SPM (SIR, 1.51; 95% confidence interval [CI], 1.34-1.70). Additionally, specific SPMs were more common among melanoma survivors, including nonmelanoma skin cancer, oral cavity and pharyngeal cancer, renal cancer, female breast cancer, lung cancer, pancreatic cancer, and liver cancer. Independent risk factors for overall SPM development included a Charlson Comorbidity Index ≥ 1 (adjusted hazard ratio [aHR], 1.41; 95% CI, 1.07-1.87), and a body mass index ≥ 25 kg/m2 (aHR, 1.47; 95% CI, 1.04-2.08). Inherent uncertainty related to diagnostic codes may exist. The risk of overall and specific SPMs was significantly elevated in Asian melanoma survivors, particularly among those with invasive melanoma. Among modifiable factors, a high body mass index (BMI) was associated with an increased risk of SPM.
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Affiliation(s)
- Joon Min Jung
- Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
| | - Do Hyung Kim
- Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
| | - Ye-Jee Kim
- Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ik Jun Moon
- Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
| | - Woo Jin Lee
- Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
| | - Sung Eun Chang
- Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
| | - Mi Woo Lee
- Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
| | - Chong Hyun Won
- Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea.
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11
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Zhang C, Chen L, Xiu Y, Zhang H, Zhang Y, Ying W. Burden of esophageal cancer in global, regional and national regions from 1990 to 2021 and its projection until 2050: results from the GBD study 2021. Front Oncol 2025; 14:1518567. [PMID: 39902130 PMCID: PMC11788179 DOI: 10.3389/fonc.2024.1518567] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Accepted: 12/27/2024] [Indexed: 02/05/2025] Open
Abstract
Background Esophageal cancer (EC) is a major global health issue characterized by high morbidity and mortality rates, with a notably low five-year survival rate. Comprehensive analyses of the global burden of EC remain limited and outdated, despite its global significance. This study aimed to systematically assess the global burden and trends of esophageal cancer across diverse populations. Methods Data on the burden of EC were collected from the Global Burden of Disease (GBD) 2021 study, including estimates of incidence, mortality, and disability-adjusted life years (DALYs), as well as risk factors, spanning 204 countries and territories. Age-standardized rates (ASRs) were calculated to allow comparisons across populations. The study further explored the relationship between EC burden and socioeconomic development by utilizing the Socio-demographic Index (SDI), aggregating data by regions. The Bayesian age-period-cohort model was applied to project future trends until 2050. Results In 2021, there were 576,529 new esophageal cancer cases, with an age-standardized incidence rate (ASIR) of 6.65 per 100,000, reflecting a 24.87% decrease since 1990. The global number of deaths reached 538,602, with an age-standardized death rate (ASDR) of 6.25 per 100,000, representing a 30.67% decline. DALYs totaled 12,999,264, corresponding to an estimated annual percentage change (EAPC) of a 1.73% decrease in the age-standardized DALYs rate. East Asia accounted for nearly two-thirds of global EC cases and deaths, while Central Sub-Saharan Africa recorded the highest ASIR and ASDR. Central Asia experienced the largest reductions, whereas Western Sub-Saharan Africa showed increasing trends. Middle-SDI countries, such as Malawi and Lesotho, had disproportionately high burdens, while high-SDI countries, including Tunisia and Kuwait, had lower burdens. Males had higher incidence and mortality rates across all age groups. By 2050, the ASIR is projected to decrease to 6.17 per 100,000, and the ASDR to 5.23 per 100,000, though the absolute number of cases and deaths is expected to rise. Conclusions The global burden of EC remains significant, with ongoing challenges in regions such as Africa and East Asia. These findings highlight the need for sustained and targeted prevention efforts, particularly in high-risk populations, to address the increasing absolute number of cases and deaths.
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Affiliation(s)
- Chengcheng Zhang
- Institute of Nursing Research, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
| | - Linzhi Chen
- Department of Nursing, Shantou University Medical College, Shantou, Guangdong, China
| | - Yuqi Xiu
- Department of Nursing, Shantou University Medical College, Shantou, Guangdong, China
| | - Hongling Zhang
- Department of Nursing, Shantou University Medical College, Shantou, Guangdong, China
| | - Yuejuan Zhang
- Nursing Research Office, The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Wenjuan Ying
- Department of Nursing, Shantou University Medical College, Shantou, Guangdong, China
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12
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Wang XM, Borsky K, Proctor DW, Goodall R, Marshall DC, Dobell W, Salciccioli JD, Matin RN, Shalhoub J, El-Muttardi N. Trends in cutaneous melanoma mortality and incidence in European Union 15+ countries between 1990 and 2019. J Eur Acad Dermatol Venereol 2025. [PMID: 39780527 DOI: 10.1111/jdv.20524] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Accepted: 11/18/2024] [Indexed: 01/11/2025]
Abstract
BACKGROUND Cutaneous melanoma (CM) is the leading cause of skin cancer mortality with associated high healthcare costs. Up-to-date reporting of epidemiological trends for CM is required to project future trends, assess the burden of disease and aid evaluation of new diagnostic, therapeutic and preventative strategies. OBJECTIVES To describe the trends in CM mortality, incidence, mortality-to-incidence indices (MIIs) and disability-adjusted life years (DALYs) over the last three decades. METHODS A population-based cross-sectional study of the Global Burden of Disease (GBD) database between 1990 and 2019 was performed. Nineteen high-income countries with similar health expenditure and classified as having high-quality mortality data including the United Kingdom, the United States, Australia and selected European Union countries were included. Annual age-standardized incidence rates (ASIRs), age-standardized death rates (ASDRs) and DALYs for each country were extracted. Mortality-to-incidence indexes were calculated by dividing the ASDR by the ASIR. Trends were described using Joinpoint regression analysis. RESULTS Almost all countries demonstrated increasing ASDR in males over the observation period with greatest percentage increase in Greece (+87%), and there was greater heterogeneity between countries in females. CM mortality was greater for males than females in all countries. Most recent Joinpoint analysis shows significantly decreasing mortality in all countries except the United Kingdom (+0.5% males between 2007 and 2019, +0.1% females between 2002 and 2019). Incidence rates increased in all countries, with evidence of plateau from 2015 onwards. While MIIs cannot be used as a proxy for survival, statistically significant decreases in MII were observed in all countries. Overall, DALYs remained static. CONCLUSIONS Over the past 30 years, CM mortality and incidence has increased in most EU15+ countries. There is evidence that in recent years, CM mortality is decreasing. The burden of disease as assessed using DALYs has remained mostly unchanged. Future work should not solely focus on expensive innovative therapies, but also on optimizing primary prevention.
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Affiliation(s)
- Xingyue M Wang
- Royal Marsden Hospital NHS Foundation Trust, Surrey, UK
- Medical Data Research Collaborative, London, UK
| | - Kim Borsky
- Medical Data Research Collaborative, London, UK
- Department of Plastic Surgery, Salisbury Foundation NHS Trust, Salisbury, UK
| | - Dominic W Proctor
- Medical Data Research Collaborative, London, UK
- Imperial College Healthcare NHS Trust, London, UK
| | - Richard Goodall
- Medical Data Research Collaborative, London, UK
- St Andrews Centre for Burns and Plastic Surgery, Broomfield Hospital, Chelmsford, Essex, UK
| | - Dominic C Marshall
- Medical Data Research Collaborative, London, UK
- National Heart and Lung Institute, Imperial College London, London, UK
| | - William Dobell
- Medical Data Research Collaborative, London, UK
- Imperial College Healthcare NHS Trust, London, UK
| | - Justin D Salciccioli
- Medical Data Research Collaborative, London, UK
- Division of Pulmonary and Critical Care, Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Rubeta N Matin
- Medical Data Research Collaborative, London, UK
- Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - Joseph Shalhoub
- Medical Data Research Collaborative, London, UK
- Imperial Vascular Unit, Imperial College Healthcare NHS Trust, London, UK
| | - Naguib El-Muttardi
- St Andrews Centre for Burns and Plastic Surgery, Broomfield Hospital, Chelmsford, Essex, UK
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13
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Lu F, Yan G, Zhao Z, Zheng Z, Wu Y, Wen L, Liu Y, Zeng Q, Zhang G. TDO2 + cancer-associated fibroblasts mediate cutaneous squamous cell carcinoma immune escape via impeding infiltration of CD8 + T cells. Cancer Immunol Immunother 2025; 74:67. [PMID: 39751882 PMCID: PMC11698999 DOI: 10.1007/s00262-024-03921-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Accepted: 12/09/2024] [Indexed: 01/04/2025]
Abstract
Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer, originating from the malignant proliferation of squamous epithelial cells. However, its pathogenesis remains unclear. To further explore the mechanisms underlying cSCC, we analyzed the data from one single-cell RNA sequencing study and discovered a significant upregulation of tryptophan 2,3-dioxygenase (TDO2) in the cancer-associated fibroblasts (CAFs). Nonetheless, the specific expression and potential biological significance of TDO2 in cSCC have not yet been reported. In this study, we confirmed that TDO2 is highly expressed in CAFs of cSCC. Clinical correlation analysis indicated that high TDO2 expression was significantly associated with poor tumor differentiation. Furthermore, increased TDO2 expression in cSCC correlated with reduced CD8 + T cell infiltration, suggesting its role in modulating immune responses. TDO2 inhibitors significantly reduced the size and number of tumors in mice and effectively increased CD8 + T cell infiltration. RNA sequencing analysis revealed that TDO2 inhibitors modulate immune cell activity and downregulate the PI3K-Akt signaling pathway. In summary, our study demonstrates that TDO2 + CAFs induce immune evasion by inhibiting CD8 + T cell infiltration in cSCC. Inhibiting TDO2 could enhance antitumor immune responses, providing a promising strategy to improve treatment outcomes in cSCC.
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Affiliation(s)
- Fangqi Lu
- Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, 200443, China
| | - Guorong Yan
- Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, 200443, China
| | - Zijun Zhao
- Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, 200443, China
| | - Zhe Zheng
- Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, 200443, China
| | - Yuhao Wu
- Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, 200443, China
| | - Long Wen
- Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, 200443, China
| | - Yeqaing Liu
- Department of Pathology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, 200443, China
| | - Qingyu Zeng
- Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, 200443, China.
| | - Guolong Zhang
- Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, 200443, China.
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14
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Sun Y, Shen Y, Liu Q, Zhang H, Jia L, Chai Y, Jiang H, Wu M, Li Y. Global trends in melanoma burden: A comprehensive analysis from the Global Burden of Disease Study, 1990-2021. J Am Acad Dermatol 2025; 92:100-107. [PMID: 39343306 DOI: 10.1016/j.jaad.2024.09.035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Revised: 08/17/2024] [Accepted: 09/03/2024] [Indexed: 10/01/2024]
Abstract
BACKGROUND Melanoma, a significant global health concern, has shown evolving epidemiologic trends. Accurate estimation of melanoma's burden is essential for public health strategies and interventions. OBJECTIVES This study aims to estimate the incidence, mortality, and disability-adjusted life years for melanoma, stratified by region, gender, and age group, from 1990 to 2021. METHODS Using data from the Global Burden of Disease 2021, we analyzed melanoma incidence, mortality rates, and disability-adjusted life years in 204 countries from 1990 to 2021. These metrics were age-standardized and stratified by age, sex, Socio-Demographic Index, region, and country. The estimated annual percentage change was calculated to track temporal trends. RESULTS Our study shows a substantial global increase in melanoma incidence, with significant disparities between genders and age groups. Higher Socio-Demographic Index regions had increased incidence rates, while global mortality declined, likely due to improved detection and treatment. LIMITATIONS The reliance on estimates and models may introduce bias due to variability in disease definitions, diagnostic criteria, and data collection methods. CONCLUSION This study underscores the dynamic nature of melanoma's burden and the need for targeted, age-specific, and gender-specific interventions. Continued research is essential to address the growing challenges posed by melanoma.
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Affiliation(s)
- Yulin Sun
- Department of Plastic Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Yiming Shen
- Department of Otology and Skull Base Surgery, Eye, Ear, Nose, and Throat Hospital, Fudan University, Shanghai, China
| | - Qian Liu
- Department of Stomatology, Sijing Hospital, Shanghai, China
| | - Hao Zhang
- Department of Histology and Embryology, College of Basic Medical Sciences, Naval Medical University, Shanghai, China
| | - Lingling Jia
- Department of Plastic Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Yi Chai
- Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China; The Hong Kong Jockey Club Centre for Suicide Research and Prevention, The University of Hong Kong, Hong Kong SAR, China; School of Public Health, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong, China
| | - Hua Jiang
- Department of Plastic Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
| | - Minjuan Wu
- Department of Histology and Embryology, College of Basic Medical Sciences, Naval Medical University, Shanghai, China.
| | - Yufei Li
- Department of Plastic Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
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15
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Zhu Y, Yang H, An Z. Skin cancer associated with calcineurin inhibitors treatment: analysis of FAERS database. Expert Opin Drug Saf 2024:1-7. [PMID: 39714133 DOI: 10.1080/14740338.2024.2443783] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Revised: 10/31/2024] [Accepted: 11/08/2024] [Indexed: 12/24/2024]
Abstract
BACKGROUND Several studies have indicated a potential link between calcineurin inhibitors (CNIs) and skin cancers. However, comprehensive evidence of CNI-induced skin cancers remains lacking. RESEARCH DESIGN AND METHODS We conducted an observational retrospective pharmacovigilance study utilizing the FAERS database to identify potential risk signals associated with skin cancers with CNIs treatment, encompassing data from its inception to the third quarter of 2023. The assessment was carried out using the Information Component (IC) and Reporting Odds Ratio (ROR). RESULTS We identified 1339 cases of skin cancers linked to CNIs use. The frequency of skin cancers associated with both CsA and Tac was significantly higher compared to all other drugs in the database, especially for nonmelanoma skin cancer (NMSC). There was no significant difference in the risk of CsA-related melanoma skin cancer (MSC) and NMSC compared to Tac. Additionally, the development of MSC appeared to have a higher risk of fatal outcomes in individuals of Caucasian descent and patients aged 40-79 years. CONCLUSIONS Our study has provided new real-world evidence regarding the safety of CNIs concerning skin cancers. It is recommended that clinicians remain vigilant about CNI-associated skin cancers and implement early surveillance to prevent adverse outcomes.
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Affiliation(s)
- Yuezhen Zhu
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
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16
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Nervil GG, Vestergaard T, Klausen S, Tolsgaard MG, Ternov NK, Hölmich LR. Impact of skin biopsy practices: A comprehensive nationwide study on skin cancer and melanoma biopsies. J Eur Acad Dermatol Venereol 2024. [PMID: 39394835 DOI: 10.1111/jdv.20371] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2024] [Accepted: 09/06/2024] [Indexed: 10/14/2024]
Abstract
BACKGROUND Due to a multitude of factors, skin cancer incidence is increasing and challenges medical professionals in biopsy decision-making. While skin cancer may have a profound impact on the patient and be costly for society, there is little knowledge about the number and cost of benign skin lesions biopsied as collateral damage. OBJECTIVES This study evaluates the number and costs of skin biopsies in Denmark over 15 years, focusing on benign and malignant skin lesions and melanomas across medical settings. It aims to determine the benign to malignant ratio (BMR) and number needed to biopsy (NNB) and estimate the direct cost of benign skin lesion biopsies in the Cancer Pathway from the perspective of a public healthcare system. METHODS The study included 4,481,207 biopsy specimens from January 2007 to June 2022 from the Danish Pathology Data Bank, of which 151,988 from the Cancer Pathway were included in the primary analysis of BMR. The national reimbursement rates for biopsies were used, alongside histopathological examination costs extracted from several pathology departments, for a Monte-Carlo simulation of a simple cost and sensitivity analysis. RESULTS The number of biopsies increased by 39.1% from 2007 to 2021. Overall BMR for malignancy was 4.1:1, and NNB for melanoma was 31.8, but biopsies performed on clinical suspicion of malignancy or melanoma had a BMR and NNB of 1.5:1 and 2.8, respectively. The cost of benign skin biopsies performed on suspicion of cancer or melanoma in 2021 was €6.6M, predominantly in hospitals. CONCLUSION A healthcare system that employs filtering functions before biopsy of skin lesions can achieve some of the lowest BMR reported in the world, but with most benign skin lesion excisions due to suspicion of malignancy performed in the expensive hospital setting. Including clinical reason for biopsy in diagnostic accuracy studies using NNB is crucial.
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Affiliation(s)
- G G Nervil
- Department of Plastic Surgery, Copenhagen University Hospital - Herlev and Gentofte, Denmark
| | - T Vestergaard
- Department of Dermatology and Allergy Centre, Odense University Hospital, Odense, Denmark
| | - S Klausen
- Department of Pathology, Copenhagen University Hospital - Herlev and Gentofte, Denmark
| | - M G Tolsgaard
- Copenhagen Academy for Medical Education and Simulation, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
- Department of Obstetrics, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - N K Ternov
- Department of Plastic Surgery, Copenhagen University Hospital - Herlev and Gentofte, Denmark
| | - L R Hölmich
- Department of Plastic Surgery, Copenhagen University Hospital - Herlev and Gentofte, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
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17
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Qian H, Gong R, Li Y, Zhu J, Wang L. A genetically informed study reveals modifiable pathways in skin cancer. J Transl Med 2024; 22:916. [PMID: 39379979 PMCID: PMC11463105 DOI: 10.1186/s12967-024-05719-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Accepted: 10/02/2024] [Indexed: 10/10/2024] Open
Abstract
BACKGROUND Identifying modifiable risk factors is essential for the prevention of skin cancer; however, establishing causality can be challenging in conventional epidemiological studies. This study aimed to determine the causal associations of potentially modifiable risk factors with skin cancer using Mendelian randomization (MR). METHODS Genetic instruments for 53 risk factors, including socioeconomic status, dietary and lifestyle factors, anthropometric measures, medication use, and comorbidities, were identified from previous genome-wide association studies. Two-sample MR analyses were performed using summary statistics for three major types of skin cancer: melanoma, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). Findings were verified using multiple MR methods under different assumptions and replication datasets. RESULTS Genetic liability to sunburn occasions, actinic keratosis, and prior skin cancers was associated with a higher risk of all three types of skin cancer, whereas genetic liability to vitiligo was associated with a lower risk. For specific skin cancer types, genetically predicted higher nevus counts and occupational class were associated with an increased risk of melanoma. Genetic liability to rheumatoid arthritis, type 2 diabetes, and increased physical activity were associated with a lower risk of BCC. Genetically predicated body mass index showed a negative association with BCC, and a positive association with SCC. CONCLUSIONS Our study reaffirmed several previously established risk factors and identified novel potential risk factors for skin cancer. Further work is needed to unravel the biological pathways in different skin cancer types and translate our findings to inform public health policies.
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Affiliation(s)
- Huan Qian
- Department of Plastic Surgery, The Second Affiliated Hospital, Medical School, Zhejiang University, Hangzhou, China
| | - Ruicheng Gong
- Department of Epidemiology and Health Statistics, School of Public Health, Hangzhou Medical College, Hangzhou, China
| | - Yingjun Li
- Department of Epidemiology and Health Statistics, School of Public Health, Hangzhou Medical College, Hangzhou, China
| | - Jiahao Zhu
- Department of Epidemiology and Health Statistics, School of Public Health, Hangzhou Medical College, Hangzhou, China
| | - Lu Wang
- Starbody Plastic Surgery Clinic, No. 271 South Hushu Road, Hushu District, Hangzhou, Zhejiang, 310007, China.
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18
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Gallagher C, O’Connor C, Gilhooley E, Bourke J, Murphy M. Beliefs, behaviours, and attitudes towards tanning and melanoma in the Irish population. SKIN HEALTH AND DISEASE 2024; 4:e398. [PMID: 39355732 PMCID: PMC11442063 DOI: 10.1002/ski2.398] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/20/2024] [Revised: 03/02/2024] [Accepted: 05/17/2024] [Indexed: 10/03/2024]
Abstract
Background The incidence of melanoma continues to rise in Ireland. Skin cancer prevention campaigns rely on promoting knowledge to improve sun-related behaviour. Objectives To explore beliefs, behaviours, and attitudes towards tanning, and confidence in identifying signs of melanoma in the Irish population. Methods A cross-sectional study was performed via an online questionnaire, with questions related to tanning, sun exposure, and skin cancer behaviours. Respondents were recruited according to gender, age and geographic region. Results The questionnaire was completed by 1043 respondents (response rate 85%). Mean age was 41 years (range 20-72 years). Participants had mixed awareness of risk reduction strategies for melanoma but had high perceived concerns about developing melanoma. However, 48.9% regularly sunbathed when sunny in Ireland and 41.5% had used tanning beds. The most common reason for not photoprotecting while sunbathing was because it prevented tanning. Nearly half (45.9%) of those who sunbathed agreed that it was worth getting sunburned to get a tan, and 69.4% reported feeling and looking better with a tan. Less than half (42.4%) felt confident about what to look for when checking their skin for melanoma. Conclusions This study underscores the importance of addressing the cultural and aesthetic aspects of sun-tanning behaviour in skin cancer prevention efforts, as well as increasing awareness of skin cancer signs and self-examination. Further research into the potential addictive nature of UV-seeking behaviour may offer new avenues for intervention and support for individuals who are addicted to tanning.
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Affiliation(s)
| | - Cathal O’Connor
- DermatologySouth Infirmary Victoria University HospitalCorkIreland
- MedicineUniversity College CorkCorkIreland
- INFANT Research CentreUniversity College CorkCorkIreland
| | - Eimear Gilhooley
- DermatologySouth Infirmary Victoria University HospitalCorkIreland
| | - John Bourke
- DermatologySouth Infirmary Victoria University HospitalCorkIreland
- MedicineUniversity College CorkCorkIreland
| | - Michelle Murphy
- DermatologySouth Infirmary Victoria University HospitalCorkIreland
- MedicineUniversity College CorkCorkIreland
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Ding L, Peng L, Huang K, Qu S, Li D, Yao J, Yang F, Zhu H, Zhao S. Single cell transcriptomics reveals dysregulated immnue homeostasis in different stages in HPV-induced cutaneous squamous cell carcinoma. Exp Dermatol 2024; 33:e15178. [PMID: 39385326 DOI: 10.1111/exd.15178] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Revised: 08/04/2024] [Accepted: 08/30/2024] [Indexed: 10/12/2024]
Abstract
In order to explore the huge impact of impaired immnue homeostasis on the occurrence and development of cutaneous squamous cell carcinoma (cSCC), and investigate characterization of the cellular components and their changes which is crucial to understanding the pathologic process of HPV-induced cSCC, we diagnosed and followed up on a very rare HPV-induced cSCC patient who progressed at a very fast rate and transferred to death quickly. We performed single-cell RNA sequencing (scRNA-seq) of 11 379 cells from the skin tissues of this patient with four different skin statuses after HPV infection. Immunofluorescence experiments were used for validation. scRNA-seq identified that CD52+ HLA-DOA- macrophages only existed in paracancerous cutaneous squamous cell carcinoma (pc-cSCC) and cSCC tissue. Besides, immune cells including CD8+ exhausted T cells and CD4+ regulatory T cells as well as matrix cells like MMP1+, and MMP11+ fibroblasts were gradually increased. Meanwhile, COMP+ ASPN+ fibroblasts gradually decreased. Cell interaction analysis revealed enhancement in interactions between monocytes/macrophages, fibroblasts and tumour-specific keratinocytes. scRNA-seq was performed in HPV-induced cSCC for the first time, to explore the correlation between infection and tumour. It is the first time to study the development of tumours from different stages of infection in HPV-induced cSCC. In this study, the tumour itself and the tumour microenvironment were both analysed and explored. And it was validated in clinical samples from different patients. Our findings reveal the dynamic immnue homeostasis from normal skin to cSCC tissue, this alteration might drive HPV-induced cSCC.
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Affiliation(s)
- Liqing Ding
- The Department of Rheumatology and Immunology, Xiangya Hospital of Central South University, Changsha, Hunan, China
- Provincial Clinical Research Center for Rheumatic and Immunologic Diseases, Xiangya Hospital, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, China
| | - Lanyuan Peng
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Kai Huang
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, Changsha, Hunan, China
- Hunan Engineering Research Center of Skin Health and Disease, Central South University, Changsha, Hunan, China
- Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Shunlin Qu
- Pathophysiology Department, Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, Hengyang Medical School, University of South China, Hengyang, Hunan, China
| | - Dongjie Li
- Provincial Clinical Research Center for Rheumatic and Immunologic Diseases, Xiangya Hospital, Changsha, Hunan, China
| | | | | | - Honglin Zhu
- The Department of Rheumatology and Immunology, Xiangya Hospital of Central South University, Changsha, Hunan, China
- Provincial Clinical Research Center for Rheumatic and Immunologic Diseases, Xiangya Hospital, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, China
| | - Shuang Zhao
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, Changsha, Hunan, China
- Hunan Engineering Research Center of Skin Health and Disease, Central South University, Changsha, Hunan, China
- Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha, Hunan, China
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20
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Taylor KME, Woodie B, Neltner SA, Fleischer AB. Transition to Medicare Does Not Contribute to Rise in Outpatient Visits for Nonmelanoma Skin Cancer, Actinic Keratosis, or Actinic Cheilitis in the US Population. Dermatol Surg 2024; 50:821-824. [PMID: 38687893 DOI: 10.1097/dss.0000000000004217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/02/2024]
Abstract
BACKGROUND Outpatient visits for nonmelanoma skin cancer (NMSC) and actinic keratoses (AK) have risen steadily in the United States, notably among Medicare beneficiaries. Individuals may delay seeking care for minimally symptomatic conditions until they qualify for Medicare coverage, indicating potential delay of nonurgent screening interventions for uninsured or underinsured patients younger than 65 years. OBJECTIVE This study investigates whether an atypical increase in outpatient visits for NMSC, AK, or actinic cheilitis (AC) occurs at the age of Medicare transition by utilizing the National Ambulatory Care Survey from 1993 to 2019. MATERIALS AND METHODS The National Ambulatory Care Survey data were analyzed for patients aged within 5 years of 65 years. Diagnoses were identified using International Classification of Diseases codes. Linear regression and outlier detection were used to identify a relationship between Medicare eligibility and outpatient visits for NMSC and AK/AC. RESULTS Predicted visits for AK/AC and NMSC increased with age. However, there was no evidence of a disproportionate increase in outpatient visits for NMSC and AK/AC at the age of Medicare eligibility. CONCLUSION Outside evidence indicates health care utilization increases after Medicare transition. This study's data do not support a corresponding rise in outpatient visits for NMSC and AK/AC at the age of Medicare eligibility.
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Affiliation(s)
| | - Brad Woodie
- University of Cincinnati College of Medicine, Cincinnati, OH
| | - Scott A Neltner
- Dermatology, University of Cincinnati College of Medicine, Cincinnati, OH
| | - Alan B Fleischer
- Dermatology, University of Cincinnati College of Medicine, Cincinnati, OH
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21
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Lim HW, Passeron T, Goh CL, Kang HY, Ly F, Morita A, Ocampo-Candiani J, Puig S, Schalka S, Wei L, Demessant AL, Le Floc'h C, Kerob D, Dreno B, Krutmann J. Evaluating the Frequency of Mole Checks by a Dermatologist and Correlated Variables in a Global Survey across 17 Countries: HELIOS Project. Acta Derm Venereol 2024; 104:adv40929. [PMID: 39177162 PMCID: PMC11358839 DOI: 10.2340/actadv.v104.40929] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2024] [Accepted: 07/03/2024] [Indexed: 08/24/2024] Open
Abstract
Secondary prevention of skin cancer consists in early detection of malignant lesions through patients' mole self-examination and medical examination. The objective of this study was to assess the self-reported frequency of mole examination in a large, representative sample of the adult general population of 17 countries from all continents. Of a total of 17,001 participants, 4.8% had their moles checked by a dermatologist more than once a year, 11.3% once a year, 8.4% every 2-3 years, 12.4% once in a while, 10.3% once in lifetime, and 52.6% of participants had never performed a mole examination. Egypt was the country with the highest prevalence of people who performed a moles check more than once a year (15.9%), followed by Brazil and the USA. A higher frequency of mole checks was associated with sex (man vs woman), higher education, higher income, fair phototype, history of skin cancer, medical insurance, and sun-protective behaviours. Despite recommendations by health providers, it appears that the frequency of mole checks in the general population is still low. It is necessary for dermatologists to keep informing at-risk populations about the importance of moles check, with particular care regarding categories that less frequently adhere to secondary prevention measures.
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Affiliation(s)
| | - Thierry Passeron
- 2. Department of Dermatology, Côte d'Azur University, Nice University Hospital Center, Nice, France; INSERM U1065, C3M, Côte d'Azur University, Nice, France
| | | | - Hee Young Kang
- Department of Dermatology, Ajou University School of Medicine, Suwon, South Korea
| | - Fatimata Ly
- Department of Dermatology, Cheikh Anta Diop Dakar University, EPS Institute of Social Hygiene, Dakar, Senegal
| | - Akimichi Morita
- Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Jorge Ocampo-Candiani
- Universidad Autonoma de Nuevo León, Facultad de Medicina, University Hospital, "Dr. Jose E. González", Monterrey, Mexico
| | - Susana Puig
- Dermatology Department, Hospital Clinic de Barcelona, Barcelona University, Barcelona, Spain
| | - Sergio Schalka
- Medecin Skin Research Center and Biochemistry Department, Chemistry Institute of Sao Paulo University, Sao Paulo, Brazil
| | - Liu Wei
- Department of Dermatology, The General Hospital of Air Force PLA, Beijing, China
| | | | | | | | - Brigitte Dreno
- Nantes University, Univ Angers, INSERM, Immunology and New Concepts in ImmunoTherapy, INCIT, UMR 1302,0 Nantes, France
| | - Jean Krutmann
- IUF Leibniz Research Institute for Environmental Medicine, Duesseldorf, Germany
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22
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Troeltzsch D, Neckel N, Neyer J, Preissner S, Raguse JD, Motzkus Y, Heiland M, Vach K, Nahles S. Clinical and social success in epithetic ear rehabilitation - Retrospectively evaluating the long-term survival of auricular implants. J Craniomaxillofac Surg 2024; 52:884-889. [PMID: 39019745 DOI: 10.1016/j.jcms.2024.02.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Revised: 11/25/2023] [Accepted: 02/01/2024] [Indexed: 07/19/2024] Open
Abstract
PURPOSE The aim of this study was to evaluate existing staging recommendations for peri-implantitis and its applicability for auricular bone anchoring. MATERIALS AND METHODS In this cross-sectional study, 44 patients treated with 47 ear epitheses and 128 implants were analyzed over 191.6 months (mean). Peri-implant sulcus depth, sulcus fluid flow rate, and peri-implant skin reaction, as well as cleaning habits and patients' quality of life, were analyzed. Mixed effect linear and mixed effect ordered logistic regression models were used. RESULTS Two of the 128 implants were lost (1.6 %). A total of 14.5 % of all patients presented light erythemas, 19.4 % showed stage 2, 4.8 % stage 3, and 12.9 % an acute infection according to Holgers. A correlation between skin reaction and sulcus fluid flow rate was observed, when grouping patients with acute signs of inflammation. Concerning patient satisfaction, 58.1 % of the patients were highly satisfied with their epitheses, 39.5 % very satisfied, and one patient was just satisfied. Younger age correlated with lower satisfaction rates. CONCLUSION Implant-retained auricular epitheses are a safe, highly sufficient and satisfying way of extending ear reconstruction. Sulcus depth and skin reaction are quick and valuable assessment tools in auricular implants, but skin reaction alone was clinically insufficient to predict peri-implant pocket inflammation.
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Affiliation(s)
- D Troeltzsch
- Department of Oral and Maxillofacial Surgery, (Head: Prof. Dr. Dr. M. Heiland), Charité-Universitätsmedizin Berlin, Berlin, Germany.
| | - N Neckel
- Department of Oral and Maxillofacial Surgery, (Head: Prof. Dr. Dr. M. Heiland), Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - J Neyer
- Department of Oral and Maxillofacial Surgery, (Head: Dr. Dr. T. Teltzrow), Klinikum Ernst von Bergmann Gemeinnützige GmbH, Charlottenstraße 72, 14467, Potsdam, Germany
| | - Saskia Preissner
- Department of Oral and Maxillofacial Surgery, (Head: Prof. Dr. Dr. M. Heiland), Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - J-D Raguse
- Department of Oral and Maxillofacial Surgery, (Head: PD Dr. Dr. J-D Raguse), Fachklinik Hornheide, Dorbaumstrasse 300, 48157, Münster, Germany
| | - Y Motzkus
- Berliner Zentrum für Künstliche Gesichtsteile/ BZkG, Augustenburger Platz 1, 13353, Berlin, Germany
| | - M Heiland
- Department of Oral and Maxillofacial Surgery, (Head: Prof. Dr. Dr. M. Heiland), Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - K Vach
- Department of Operative Dentistry and Periodontology, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - S Nahles
- Department of Oral and Maxillofacial Surgery, (Head: Prof. Dr. Dr. M. Heiland), Charité-Universitätsmedizin Berlin, Berlin, Germany
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23
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Maximino JA, Mayer A, Lourenço A, Soares RO, Pojo M. Skin cancer screening: the experience in South Portugal. Int J Dermatol 2024; 63:1056-1063. [PMID: 38323503 DOI: 10.1111/ijd.17065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Revised: 01/16/2024] [Accepted: 01/16/2024] [Indexed: 02/08/2024]
Abstract
BACKGROUND The number of skin cancer cases and related deaths continues to increase worldwide, including in Portugal. The lack of efficient health care leaves the southern Portuguese population at risk of presenting skin lesions at later stages. An initiative for skin cancer screening and medical care follow-up was created by the nonprofit organization Liga Portuguesa Contra o Cancro - Núcleo Regional do Sul (LPCC-NRS). METHODS Information was gathered from 4,398 participants in several Southern Portugal regions, from January 2021 to July 2022. Descriptive and lesion risk statistical analyses were applied. RESULTS Participants' characteristics were described, and risk assessment was performed differentially between premalignant (n = 577) and malignant lesions (n = 176). The main risk factor for both was male gender. From the described suspicious malignant lesions, 31.8% were confirmed (n = 56), among which there were 43 basal cell carcinomas (BCC), 9 cutaneous melanomas (CM), and 4 squamous cell carcinomas (SCC). CONCLUSIONS Data analysis pointed to a need for improved participant recruitment, especially of male participants, and health literacy assessment in future screenings.
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Affiliation(s)
- José A Maximino
- Liga Portuguesa Contra o Cancro - Núcleo Regional do Sul, Lisbon, Portugal
| | - Alexandra Mayer
- Registo Oncológico Nacional (RON), Instituto Português de Oncologia de Lisboa Francisco Gentil, EPE, Rua Professor Lima Basto, Lisbon, Portugal
| | - António Lourenço
- Registo Oncológico Nacional (RON), Instituto Português de Oncologia de Lisboa Francisco Gentil, EPE, Rua Professor Lima Basto, Lisbon, Portugal
| | - Rui O Soares
- Liga Portuguesa Contra o Cancro - Núcleo Regional do Sul, Lisbon, Portugal
| | - Marta Pojo
- Liga Portuguesa Contra o Cancro - Núcleo Regional do Sul, Lisbon, Portugal
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24
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Wall J, Gadsby‐Davis K, Mistry K, Levell NJ, Venables ZC. Impact of the COVID-19 pandemic on international cutaneous squamous cell carcinoma incidence: A systematic review and meta-analysis. SKIN HEALTH AND DISEASE 2024; 4:e405. [PMID: 39104659 PMCID: PMC11297431 DOI: 10.1002/ski2.405] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Revised: 05/09/2024] [Accepted: 06/04/2024] [Indexed: 08/07/2024]
Abstract
Background Non-melanoma skin cancer (NMSC) is the most common cancer globally in white ethinicity populations, and cutaneous squamous cell carcinoma (cSCC) is the second most common subtype. The COVID-19 pandemic severely impacted public and private healthcare systems. Many studies have reported reduced cancer diagnoses during the pandemic. The impact of the COVID-19 pandemic on global cSCC and NMSC incidence is poorly reported. Objectives The aim was to conduct a systematic review and meta-analysis to assess the impact of the COVID-19 pandemic on global cSCC and NMSC incidence rates, compared with 2019 incidence rates. Two primary outcome measures were used: crude incidence rate ratios (CIRR) and age-standardised incidence rate ratios (ASIRR). Methods A structured search was undertaken on 23 March 2023 using grey literature and four electronic databases: MEDLINE, CINAHL, EMBASE and Web of Science. Studies published before January 2020 were excluded. A quality assessment was undertaken using A. Lomas quality assessment tool. CIRR outcomes were synthesised in a meta-analysis, while ASIRR outcomes were narratively synthesised. Results Fourteen cancer registries were included, capturing data from 13 countries across Europe. Variation was observed in NMSC and cSCC incidence across the cancer registries. Pooled cSCC crude incidence rates in 2020 were equal to crude incidence rates in 2019 (cSCC-CIRR 1.00 (95% confidence interval (CI) 0.94-1.06). In 2021, the pooled result indicated a non-significant 8% increase in cSCC crude incidence rates, compared with 2019 (cSCC-CIRR 1.08 (95% CI 0.98-1.19). Significant reductions were reported in NMSC incidence across all meta-analyses in 2020 and 2021 compared with 2019. Heterogeneity was observed across most pooled estimates (I 2>75%). Conclusion There was a lack of high quality data on cSCC incidence rates recorded during the pandemic outside of Europe. The COVID-19 pandemic resulted in no significant changes in cSCC incidence across Europe. By contrast, NMSC incidence fell across Europe following the pandemic. Significant reductions in pooled NMSC incidence rates may reflect a delay in basal cell carcinoma presentation, diagnosis and treatment. Although annual incidence rates for cSCC were not affected by the pandemic, delays in treatment may still have occurred, which may result in poorer outcomes yet to be fully understood.
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Affiliation(s)
- James Wall
- University of East AngliaNorwich Medical SchoolNorwichUK
| | | | - Khaylen Mistry
- University of East AngliaNorwich Medical SchoolNorwichUK
- DermatologyNorfolk and Norwich University Hospitals NHS Foundation TrustNorwichUK
| | - Nick J. Levell
- University of East AngliaNorwich Medical SchoolNorwichUK
- DermatologyNorfolk and Norwich University Hospitals NHS Foundation TrustNorwichUK
| | - Zoe C. Venables
- University of East AngliaNorwich Medical SchoolNorwichUK
- DermatologyNorfolk and Norwich University Hospitals NHS Foundation TrustNorwichUK
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25
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Chandanwale SS, Singh M, Raj A, Viswanathan V, Bharadwaj S. A Giant Basal-Cell Carcinoma: A Rare Subtype at a Rare Site. Int J Appl Basic Med Res 2024; 14:202-204. [PMID: 39310074 PMCID: PMC11412559 DOI: 10.4103/ijabmr.ijabmr_488_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Revised: 04/15/2024] [Accepted: 06/10/2024] [Indexed: 09/25/2024] Open
Abstract
Giant basal-cell carcinoma (BCC) is a rare subtype of BCC which is characterized by aggressive biological behavior with extensive local invasion, frequent metastasis, and poor prognosis. It arises almost exclusively on hair-bearing skin. It has been rarely reported on sole. Various pathogenic factors such as arsenic exposure, ionizing radiation, repeated trauma, and hereditary syndromes have been implicated. A combination of optical coherence tomography and reflectance confocal microscopy can provide useful information for both depth and horizontal extension of tumor and could be used before surgery to explore subclinical extension. Wide local excision of the lesion with histologically confirmed negative margins for the reconstruction of the defect, followed by adjuvant chemoradiation gives a better outcome compared to radiotherapy or chemotherapy alone. Chemotherapy with cisplatin-based treatment is the most common regimen. We report a case of giant BCC on the sole in an elderly male. After excision, the defect was treated with skin grafting.
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Affiliation(s)
| | - Madhuri Singh
- Department of Pathology, Dr. D. Y. Patil Medical College, Pune, Maharashtra, India
| | - Akshi Raj
- Department of Pathology, Dr. D. Y. Patil Medical College, Pune, Maharashtra, India
| | - Vidya Viswanathan
- Department of Pathology, Dr. D. Y. Patil Medical College, Pune, Maharashtra, India
| | - Saloni Bharadwaj
- Department of Pathology, Dr. D. Y. Patil Medical College, Pune, Maharashtra, India
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26
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Brorsen LF, McKenzie JS, Pinto FE, Glud M, Hansen HS, Haedersdal M, Takats Z, Janfelt C, Lerche CM. Metabolomic profiling and accurate diagnosis of basal cell carcinoma by MALDI imaging and machine learning. Exp Dermatol 2024; 33:e15141. [PMID: 39036889 DOI: 10.1111/exd.15141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Revised: 07/01/2024] [Accepted: 07/03/2024] [Indexed: 07/23/2024]
Abstract
Basal cell carcinoma (BCC), the most common keratinocyte cancer, presents a substantial public health challenge due to its high prevalence. Traditional diagnostic methods, which rely on visual examination and histopathological analysis, do not include metabolomic data. This exploratory study aims to molecularly characterize BCC and diagnose tumour tissue by applying matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) and machine learning (ML). BCC tumour development was induced in a mouse model and tissue sections containing BCC (n = 12) were analysed. The study design involved three phases: (i) Model training, (ii) Model validation and (iii) Metabolomic analysis. The ML algorithm was trained on MS data extracted and labelled in accordance with histopathology. An overall classification accuracy of 99.0% was reached for the labelled data. Classification of unlabelled tissue areas aligned with the evaluation of a certified Mohs surgeon for 99.9% of the total tissue area, underscoring the model's high sensitivity and specificity in identifying BCC. Tentative metabolite identifications were assigned to 189 signals of importance for the recognition of BCC, each indicating a potential tumour marker of diagnostic value. These findings demonstrate the potential for MALDI-MSI coupled with ML to characterize the metabolomic profile of BCC and to diagnose tumour tissue with high sensitivity and specificity. Further studies are needed to explore the potential of implementing integrated MS and automated analyses in the clinical setting.
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Affiliation(s)
- Lauritz F Brorsen
- Department of Dermatology, Copenhagen University Hospital-Bispebjerg and Frederiksberg, Copenhagen, Denmark
- Department of Pharmacy, University of Copenhagen, Copenhagen, Denmark
| | - James S McKenzie
- Department of Digestion, Metabolism and Reproduction, Imperial College London, London, UK
| | - Fernanda E Pinto
- Department of Dermatology, Copenhagen University Hospital-Bispebjerg and Frederiksberg, Copenhagen, Denmark
| | - Martin Glud
- Department of Dermatology, Copenhagen University Hospital-Bispebjerg and Frederiksberg, Copenhagen, Denmark
| | - Harald S Hansen
- Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark
| | - Merete Haedersdal
- Department of Dermatology, Copenhagen University Hospital-Bispebjerg and Frederiksberg, Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Zoltan Takats
- Department of Digestion, Metabolism and Reproduction, Imperial College London, London, UK
| | - Christian Janfelt
- Department of Pharmacy, University of Copenhagen, Copenhagen, Denmark
| | - Catharina M Lerche
- Department of Dermatology, Copenhagen University Hospital-Bispebjerg and Frederiksberg, Copenhagen, Denmark
- Department of Pharmacy, University of Copenhagen, Copenhagen, Denmark
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27
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Attal ZG, Shalata W, Soklakova A, Tourkey L, Shalata S, Abu Saleh O, Abu Salamah F, Alatawneh I, Yakobson A. Advanced and Metastatic Non-Melanoma Skin Cancer: Epidemiology, Risk Factors, Clinical Features, and Treatment Options. Biomedicines 2024; 12:1448. [PMID: 39062023 PMCID: PMC11274597 DOI: 10.3390/biomedicines12071448] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2024] [Revised: 06/27/2024] [Accepted: 06/27/2024] [Indexed: 07/28/2024] Open
Abstract
Non-melanoma skin cancers (NMSC) form the majority of skin cancers, with basal cell carcinoma (BCC) being the most common and cutaneous squamous cell carcinoma (cSCC) being second. Prolonged ultraviolet (UV) exposure, aging, male gender, and immunosuppression represent most of the causes of this category of diseases. BCCs and cSCCs both include different types of skin cancers, such as nodular or morpheaform BCC or flat cSCC. Locally advanced and metastatic NMSCs cannot be treated surgically; thus, systemic therapy (TKI and Immunotherapy) is needed. Interestingly, NMSCs are frequently linked to abnormal Hedgehog (HH) signaling which most systemic immunotherapies for these cancers are based upon. Of note, the first line therapies of BCC, sonidegib and vismodegib, are HH inhibitors. Programmed death receptor 1 antibody (PD-1) inhibitors such as cemiplimab, pembrolizumab, and nivolumab have been approved for the treatment of cSCC. Thus, this paper reviews the epidemiology, risk factors, clinical features, and treatment options for both BCC and cSCC.
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Affiliation(s)
- Zoe Gabrielle Attal
- Medical School for International Health, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva 84105, Israel
| | - Walid Shalata
- The Legacy Heritage Center, Dr Larry Norton Institute, Soroka Medical Center, Ben Gurion University, Beer Sheva 84105, Israel
| | - Arina Soklakova
- Medical School for International Health, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva 84105, Israel
| | - Lena Tourkey
- Medical School for International Health, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva 84105, Israel
| | - Sondos Shalata
- Nutrition Unit, Galilee Medical Center, Nahariya 22000, Israel
| | - Omar Abu Saleh
- Department of Dermatology and Venereology, The Emek Medical Centre, Afula 18341, Israel
| | - Fahed Abu Salamah
- Department of Dermatology, Soroka Medical Center and Ben Gurion University, Beer Sheva 84105, Israel
| | - Ibrahim Alatawneh
- Department of Dermatology, Soroka Medical Center and Ben Gurion University, Beer Sheva 84105, Israel
| | - Alexander Yakobson
- Medical School for International Health, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva 84105, Israel
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28
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Jasmine F, Argos M, Khamkevych Y, Islam T, Rakibuz-Zaman M, Shahriar M, Shea CR, Ahsan H, Kibriya MG. Molecular Profiling and the Interaction of Somatic Mutations with Transcriptomic Profiles in Non-Melanoma Skin Cancer (NMSC) in a Population Exposed to Arsenic. Cells 2024; 13:1056. [PMID: 38920684 PMCID: PMC11201393 DOI: 10.3390/cells13121056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2024] [Revised: 05/31/2024] [Accepted: 06/14/2024] [Indexed: 06/27/2024] Open
Abstract
Exposure to inorganic arsenic (As) is recognized as a risk factor for non-melanoma skin cancer (NMSC). We followed up with 7000 adults for 6 years who were exposed to As. During follow-up, 2.2% of the males and 1.3% of the females developed basal cell carcinoma (BCC), while 0.4% of the male and 0.2% of the female participants developed squamous cell carcinoma (SCC). Using a panel of more than 400 cancer-related genes, we detected somatic mutations (SMs) in the first 32 NMSC samples (BCC = 26 and SCC = 6) by comparing paired (tissue-blood) samples from the same individual and then comparing them to the SM in healthy skin tissue from 16 participants. We identified (a) a list of NMSC-associated SMs, (b) SMs present in both NMSC and healthy skin, and (c) SMs found only in healthy skin. We also demonstrate that the presence of non-synonymous SMs in the top mutated genes (like PTCH1, NOTCH1, SYNE1, PKHD1 in BCC and TP53 in SCC) significantly affects the magnitude of differential expressions of major genes and gene pathways (basal cell carcinoma pathways, NOTCH signaling, IL-17 signaling, p53 signaling, Wnt signaling pathway). These findings may help select groups of patients for targeted therapy, like hedgehog signaling inhibitors, IL17 inhibitors, etc., in the future.
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Affiliation(s)
- Farzana Jasmine
- Institute for Population and Precision Health (IPPH), University of Chicago, Chicago, IL 60637, USA; (F.J.)
| | - Maria Argos
- Epidemiology & Biostatistics, Global Health, University of Illinois Chicago, Chicago, IL 60612, USA
| | - Yuliia Khamkevych
- Institute for Population and Precision Health (IPPH), University of Chicago, Chicago, IL 60637, USA; (F.J.)
| | - Tariqul Islam
- UChicago Research Bangladesh (URB), University of Chicago, Dhaka 1230, Bangladesh
| | | | - Mohammad Shahriar
- Institute for Population and Precision Health (IPPH), University of Chicago, Chicago, IL 60637, USA; (F.J.)
| | - Christopher R. Shea
- Division of Dermatology, Department of Medicine, University of Chicago, Chicago, IL 60637, USA
| | - Habibul Ahsan
- Institute for Population and Precision Health (IPPH), University of Chicago, Chicago, IL 60637, USA; (F.J.)
- Department of Public Health Sciences, Biological Science Division, University of Chicago, Chicago, IL 60637, USA
| | - Muhammad G. Kibriya
- Institute for Population and Precision Health (IPPH), University of Chicago, Chicago, IL 60637, USA; (F.J.)
- Department of Public Health Sciences, Biological Science Division, University of Chicago, Chicago, IL 60637, USA
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Lee J, Bao X. Comparative Review on Cancer Pathology from Aberrant Histone Chaperone Activity. Int J Mol Sci 2024; 25:6403. [PMID: 38928110 PMCID: PMC11203986 DOI: 10.3390/ijms25126403] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2024] [Revised: 06/03/2024] [Accepted: 06/06/2024] [Indexed: 06/28/2024] Open
Abstract
Histone chaperones are integral to chromatin dynamics, facilitating the assembly and disassembly of nucleosomes, thereby playing a crucial role in regulating gene expression and maintaining genomic stability. Moreover, they prevent aberrant histone interactions prior to chromatin assembly. Disruption in histone chaperone function may result in genomic instability, which is implicated in pathogenesis. This review aims to elucidate the role of histone chaperones in cancer pathologies and explore their potential as therapeutic targets. Histone chaperones have been found to be dysregulated in various cancers, with alterations in expression levels, mutations, or aberrant interactions leading to tumorigenesis and cancer progression. In addition, this review intends to highlight the molecular mechanisms of interactions between histone chaperones and oncogenic factors, underscoring their roles in cancer cell survival and proliferation. The dysregulation of histone chaperones is significantly correlated with cancer development, establishing them as active contributors to cancer pathology and viable targets for therapeutic intervention. This review advocates for continued research into histone chaperone-targeted therapies, which hold potential for precision medicine in oncology. Future advancements in understanding chaperone functions and interactions are anticipated to lead to novel cancer treatments, enhancing patient care and outcomes.
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Affiliation(s)
| | - Xiucong Bao
- School of Biomedical Sciences, Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China;
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Hossain A, Ahsan A, Hasan I, Sohel, Khan A, Somadder PD, Monjur S, Miah S, Kibria KMK, Ahmed K, Rahman H. Screening out molecular pathways and prognostic biomarkers of ultraviolet-mediated melanoma through computational techniques. Int J Biol Markers 2024; 39:118-129. [PMID: 38410032 DOI: 10.1177/03936155241230968] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/28/2024]
Abstract
PURPOSE Ultraviolet radiation causes skin cancer, but the exact mechanism by which it occurs and the most effective methods of intervention to prevent it are yet unknown. For this purpose, our study will use bioinformatics and systems biology approaches to discover potential biomarkers of skin cancer for early diagnosis and prevention of disease with applicable clinical treatments. METHODS This study compared gene expression and protein levels in ultraviolet-mediated cultured keratinocytes and adjacent normal skin tissue using RNA sequencing data from the National Center for Biotechnology Information-Gene Expression Omnibus (NCBI-GEO) database. Then, pathway analysis was employed with a selection of hub genes from the protein-protein interaction (PPI) network and the survival and expression profiles. Finally, potential clinical biomarkers were validated by receiver operating characteristic (ROC) curve analysis. RESULTS We identified 32 shared differentially expressed genes (DEGs) by analyzing three different subsets of the GSE85443 dataset. Skin cancer development is related to the control of several DEGs through cyclin-dependent protein serine/threonine kinase activity, cell cycle regulation, and activation of the NIMA kinase pathways. The cytoHubba plugin in Cytoscape identified 12 hub genes from PPI; among these 3 DEGs, namely, AURKA, CDK4, and PLK1 were significantly associated with survival (P < 0.05) and highly expressed in skin cancer tissues. For validation purposes, ROC curve analysis indicated two biomarkers: AURKA (area under the curve (AUC) value = 0.8) and PLK1 (AUC value = 0.7), which were in an acceptable range. CONCLUSIONS Further translational research, including clinical experiments, teratogenicity tests, and in-vitro or in-vivo studies, will be performed to evaluate the expression of these identified biomarkers regarding the prognosis of skin cancer patients.
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Affiliation(s)
- Arju Hossain
- Department of Biotechnology and Genetic Engineering, Mawlana Bhashani Science and Technology University, Tangail, Bangladesh
| | - Asif Ahsan
- Department of Biotechnology and Genetic Engineering, Mawlana Bhashani Science and Technology University, Tangail, Bangladesh
| | - Imran Hasan
- Department of Computer Science and Engineering, Islamic University, Kushtia, Bangladesh
| | - Sohel
- Department of Biochemistry and Molecular Biology, Primeasia University, Dhaka, Bangladesh
| | - Arif Khan
- Department of Biotechnology & Genetic Engineering, University of Development Alternative, Dhaka, Bangladesh
| | - Pratul Dipta Somadder
- Department of Biotechnology and Genetic Engineering, Mawlana Bhashani Science and Technology University, Tangail, Bangladesh
| | - Sumaiya Monjur
- Department of Otolaryngology and Head-Neck Surgery, Dhaka Medical College and Hospital, Dhaka, Bangladesh
| | - Sipon Miah
- Department of Information and communication Technology, Islamic University, Kushtia, Bangladesh
| | - K M Kaderi Kibria
- Department of Biotechnology and Genetic Engineering, Mawlana Bhashani Science and Technology University, Tangail, Bangladesh
| | - Kawsar Ahmed
- Department of Electrical and Computer Engineering, University of Saskatchewan, Saskatoon, Canada
- Group of Biophotomatiχ, Department of Information and Communication Technology, Mawlana Bhashani Science and Technology University, Tangail, Bangladesh
| | - Habibur Rahman
- Department of Computer Science and Engineering, Islamic University, Kushtia, Bangladesh
- Center for Advanced Bioinformatics and Artificial Intelligence Research, Islamic University, Kushtia, Bangladesh
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Ksienski D, Truong PT, Bone JN, Egli S, Clarkson M, Patterson T, Lesperance M, Lakkunarajah S. Advanced cutaneous squamous cell carcinoma: Impact of age on the safety and efficacy of cemiplimab and the prognostic significance of blood biomarkers. J Geriatr Oncol 2024; 15:101789. [PMID: 38710153 DOI: 10.1016/j.jgo.2024.101789] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Revised: 03/23/2024] [Accepted: 04/26/2024] [Indexed: 05/08/2024]
Abstract
INTRODUCTION Age-related differences in the safety profile of cemiplimab for patients with locally advanced or metastatic cutaneous squamous cell carcinoma (cSCC) have not been well described. We investigated the association of increasing age with immune related adverse events (irAE) from cemiplimab, efficacy outcomes, and the prognostic significance of pre-treatment blood biomarkers in contemporary practice. MATERIALS AND METHODS Patients starting first-line cemiplimab for locally advanced or metastatic cSCC at British Columbia Cancer between April 2019 and January 2023 were identified. Landmark four-month logistic regression analysis compared the odds of developing irAE or sequelae amongst patients aged <75 years to those aged 75-84 or ≥ 85. Objective responses were determined using Response Evaluation Criteria in Solid Tumors version 1.1. Univariable Cox proportional hazard (PH) regression modelling of factors associated with overall survival (OS) was performed. RESULTS Of 106 patients, the proportions aged <75, 75-84, and ≥ 85 years were 34%, 45%, and 21%, respectively. Overall, the proportion of patients with irAE ≥ grade 3, cemiplimab discontinuation, and hospitalization for immune toxicity was 27.4%, 31.1%, and 11.3%, respectively. There was no clear association between age and the odds of high grade irAE. However, increased odds of cemiplimab discontinuation was observed in patients aged 75-84 years (p = 0.05). Patients ≥85 years had increased hospitalizations due to irAE (OR = 5.00, 95% CI = 0.97-37.52) with two treatment-related deaths. Objective responses were similar across age cohorts (50.0%, 60.4%, and 54.5%) but progressive disease was higher in the age ≥ 85 group (22.2%, 18.8%, and 31.8%). On Cox PH regression analysis, age ≥ 85 years (vs. <75), Eastern Cooperative Oncology Group performance status 2-3 (vs. 0-1), and neutrophil to lymphocyte ratio (NLR) ≥7.80 (vs. <7.80) were associated with shorter survival. DISCUSSION While the odds of high grade irAE were similar across age groups, significant age-related differences in treatment discontinuation and hospitalization due to immune toxicity were observed. Despite a higher incidence of primary progression and shorter OS in the oldest cohort, cemiplimab yielded robust objective responses regardless of age. Higher pre-treatment NLR was associated with shorter survival and the cut-point identified requires further study.
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MESH Headings
- Humans
- Aged
- Aged, 80 and over
- Male
- Female
- Antibodies, Monoclonal, Humanized/therapeutic use
- Antibodies, Monoclonal, Humanized/adverse effects
- Skin Neoplasms/drug therapy
- Skin Neoplasms/blood
- Carcinoma, Squamous Cell/drug therapy
- Carcinoma, Squamous Cell/blood
- Age Factors
- Prognosis
- Antineoplastic Agents, Immunological/therapeutic use
- Antineoplastic Agents, Immunological/adverse effects
- Biomarkers, Tumor/blood
- British Columbia
- Retrospective Studies
- Middle Aged
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Affiliation(s)
- Doran Ksienski
- BC Cancer-Victoria, British Columbia, Canada; University of British Columbia, Victoria, British Columbia, Canada.
| | - Pauline T Truong
- BC Cancer-Victoria, British Columbia, Canada; University of British Columbia, Victoria, British Columbia, Canada
| | - Jeffrey N Bone
- Biostatistics, Clinical Research Support Unit, BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada
| | - Sarah Egli
- BC Cancer-Victoria, British Columbia, Canada
| | | | | | - Mary Lesperance
- University of Victoria, Department of Mathematics and Statistics, Victoria, British Columbia, Canada
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Tan Y, Zhang Y, Li JLY, Chia HY, Tan MWP, Ebel G, Leong KWK, Lim EYQ, Chong KKL, Lee BTK, Ng LG, Tey HL. Visualising cancer in 3D: 3-Dimensional Tissue Imaging for management of cutaneous basal cell carcinoma. Exp Dermatol 2024; 33:e15097. [PMID: 38840370 DOI: 10.1111/exd.15097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2024] [Revised: 04/24/2024] [Accepted: 04/26/2024] [Indexed: 06/07/2024]
Abstract
Surgical management of basal cell carcinoma (BCC) typically involves surgical excision with post-operative margin assessment using the bread-loafing technique; or gold-standard Mohs micrographic surgery (MMS), where margins are iteratively examined for residual cancer after tumour removal, with additional excisions performed upon detecting residual tumour at margins. There is limited sampling of resection margins with bread loafing, with detection of positive margins 44% of the time using 2 mm intervals. To resolve this, we have developed three-dimensional (3D) Tissue Imaging for: (1) complete examination of cancer margins and (2) detection of tumour proximity to nerves and blood vessels. 3D Tissue optical clearing with a light sheet imaging protocol was developed for margin assessment in two datasets assessed by two independent evaluators: (1) 48 samples from 29 patients with varied BCC subtypes, sizes and pigmentation levels; (2) 32 samples with matching Mohs' surgeon reading of tumour margins using two-dimensional haematoxylin & eosin-stained sections. The 3D Tissue Imaging protocol permits a complete examination of deeper and peripheral margins. Two independent evaluators achieved negative predictive values of 92.3% and 88.24% with 3D Tissue Imaging. Images obtained from 3D Tissue Imaging recapitulates histological features of BCC, such as nuclear crowding, palisading and retraction clefting and provides a 3D context for recognising normal skin adnexal structures. Concurrent immunofluorescence labelling of nerves and blood vessels allows visualisation of structures closer to tumour-positive regions, which may have a higher risk for neural and vascular infiltration. Together, this method provides more information in a 3D spatial context, enabling better cancer management by clinicians.
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Affiliation(s)
- Yingrou Tan
- National Skin Centre, National Healthcare Group, Singapore, Singapore
- Singapore Immunology Network, SIgN, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore
- Skin Research Institute of Singapore, SRIS, Agency of Science and Technology and Research (A*STAR), Singapore, Singapore
| | - Yuning Zhang
- National Skin Centre, National Healthcare Group, Singapore, Singapore
- Singapore Immunology Network, SIgN, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore
| | - Jackson Liang Yao Li
- Singapore Immunology Network, SIgN, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore
| | - Hui Yi Chia
- National Skin Centre, National Healthcare Group, Singapore, Singapore
| | | | - Gernot Ebel
- Miltenyi Biotec B.V. & Co. KG, Bielefeld, Germany
| | - Keith Weng Kit Leong
- Singapore Immunology Network, SIgN, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore
| | - Eiffer Ying Qi Lim
- National Skin Centre, National Healthcare Group, Singapore, Singapore
- Singapore Immunology Network, SIgN, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore
- School of Life Sciences and Chemical Technology, Ngee Ann Polytechnic, Singapore, Singapore
| | - Kylia Kai Ling Chong
- National Skin Centre, National Healthcare Group, Singapore, Singapore
- Singapore Immunology Network, SIgN, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore
- School of Life Sciences and Chemical Technology, Ngee Ann Polytechnic, Singapore, Singapore
| | - Bernett Teck Kwong Lee
- Singapore Immunology Network, SIgN, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
| | - Lai Guan Ng
- National Skin Centre, National Healthcare Group, Singapore, Singapore
- Singapore Immunology Network, SIgN, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore
- Shanghai Immune Therapy Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Hong Liang Tey
- National Skin Centre, National Healthcare Group, Singapore, Singapore
- Skin Research Institute of Singapore, SRIS, Agency of Science and Technology and Research (A*STAR), Singapore, Singapore
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
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Mehri M, Karazhian M, Nikyar A, Mehri R, Bagheri A, Akbari M, Roshandel G, Teimoorian M. Incidence Rates and Time Trends of Skin Cancer in Golestan Province, Northeastern Iran, 2005-2018. ARCHIVES OF IRANIAN MEDICINE 2024; 27:289-297. [PMID: 38855798 PMCID: PMC11264628 DOI: 10.34172/aim.28801] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Accepted: 04/14/2024] [Indexed: 06/11/2024]
Abstract
BACKGROUND Given the significant occurrence of skin cancer in the Middle East and the existing research gap concerning its incidence and trends, this research aimed to study the epidemiology and trend changes of skin cancer in the Golestan province, Northeastern Iran. METHODS The Golestan Population-based Cancer Registry's (GPCR's) data bank was utilized to gather information on confirmed skin cancer cases in the province during 2005-2018. We used Poisson regression analysis for comparing incidence rates between groups. P values less than 0.05 were considered statistically significant. RESULTS Of 1690 patients (mean age: 62.05±15.83 years), most were male (60.1%) and resided in urban areas (61.5%). The age-standardized rate (ASR) of non-melanoma and melanoma skin cancer was 8.49 and 0.56 per 100000 persons-year, respectively. A notably higher ASR for non-melanoma skin cancer (NMSC) was observed in men (ASR: 10.60; 95% CI: 9.91-11.29) (P<0.01) and urban residents (ASR: 10.19; 95% CI: 9.52-10.82) (P<0.01). There was no significant difference in the ASR of melanoma skin cancer based on gender (P=0.24) and place of residence (P=0.48). The incidence trend of melanoma (estimated annual percent change [EAPC]: -3.28; 95% CI: -18.54 to 14.83) and NMSC (EAPC: 0.39; 95% CI: -3.99 to 4.97) did not differ significantly. CONCLUSION During the 14-year study period, the ASR of both types of skin cancer exhibited a consistent pattern, except for NMSC, which showed higher rates among men and urban residents. This should be taken into consideration when formulating preventive and control strategies in the study area.
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Affiliation(s)
- Majid Mehri
- Department of Internal Medicine, School of Medicine, Golestan University of Medical Sciences, Gorgan, Iran
| | - Mina Karazhian
- Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran
| | - Arash Nikyar
- Department of Research and Technology, Golestan University of Medical Sciences, Gorgan, Iran
| | - Romina Mehri
- Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran
| | - Ali Bagheri
- Deputy of Public Health, Golestan University of Medical Sciences, Gorgan, Iran
| | - Mahnaz Akbari
- Deputy of Treatment, Golestan University of Medical Sciences, Gorgan, Iran
| | - Gholamreza Roshandel
- Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran
| | - Mehrdad Teimoorian
- Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran
- Stem Cell Research Center, Golestan University of Medical Sciences, Gorgan, Iran
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Huang S, Jiang J, Wong HS, Zhu P, Ji X, Wang D. Global burden and prediction study of cutaneous squamous cell carcinoma from 1990 to 2030: A systematic analysis and comparison with China. J Glob Health 2024; 14:04093. [PMID: 38695259 PMCID: PMC11063968 DOI: 10.7189/jogh.14.04093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/04/2024] Open
Abstract
Background China has the highest number of new cancer cases and deaths globally. Due to particularly low scores in health care quality for cutaneous squamous cell carcinoma (cSCC), the country's cSCC burden requires greater awareness. Consequently, we aimed to evaluate and predict the trend of the cSCC burden globally and in China from 1990 to 2030. Methods We retrieved data from the Global Burden of Disease 2019 study, which provided estimates of the incidence, mortality, prevalence, and disability-adjusted life years (DALYs) of cSCC from 1990 to 2019. We set up joint-point analyses and Bayesian age-period-cohort (BAPC) models to predict the disease burden of cSCC up to 2030. Results In 2019, China reported age-standardised rates of cSCC prevalence, incidence, mortality, and DALYs of 2.54, 2.12, 0.88, and 16.76 per 100 000 population, respectively. The country's prevalence and incidence rates from 1990 to 2019 were lower than the global levels, but its mortality and DALY rates were higher. The age-standardised rates were higher for males, and the disease burden increased with each age group globally and in China. Moreover, the average annual percentage change showed all indicators were growing faster than the global levels. According to the BAPC model, there will be an upward trend in the prevalence and incidence globally and in China between 2020 and 2030, with a decrease in mortality and DALYs. Conclusions We observed an upward trend in the cSCC burden over the past 30 years in China. Prevalence and incidence are expected to continue at a higher rate than the global average in the next decade, while mortality and DALYs are predicted to decrease. As the Chinese population ages, efforts toward managing and preventing cSCC should be targeted towards the elderly population.
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Louie L, Wise J, Berl A, Shir‐az O, Kravtsov V, Yakhini Z, Shalom A, Golberg A, Vitkin E. High-throughput lipidomic profiles sampled with electroporation-based biopsy differentiate healthy skin, cutaneous squamous cell carcinoma, and basal cell carcinoma. Skin Res Technol 2024; 30:e13706. [PMID: 38721854 PMCID: PMC11079884 DOI: 10.1111/srt.13706] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Accepted: 04/01/2024] [Indexed: 05/12/2024]
Abstract
BACKGROUND The incidence rates of cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC) skin cancers are rising, while the current diagnostic process is time-consuming. We describe the development of a novel approach to high-throughput sampling of tissue lipids using electroporation-based biopsy, termed e-biopsy. We report on the ability of the e-biopsy technique to harvest large amounts of lipids from human skin samples. MATERIALS AND METHODS Here, 168 lipids were reliably identified from 12 patients providing a total of 13 samples. The extracted lipids were profiled with ultra-performance liquid chromatography and tandem mass spectrometry (UPLC-MS-MS) providing cSCC, BCC, and healthy skin lipidomic profiles. RESULTS Comparative analysis identified 27 differentially expressed lipids (p < 0.05). The general profile trend is low diglycerides in both cSCC and BCC, high phospholipids in BCC, and high lyso-phospholipids in cSCC compared to healthy skin tissue samples. CONCLUSION The results contribute to the growing body of knowledge that can potentially lead to novel insights into these skin cancers and demonstrate the potential of the e-biopsy technique for the analysis of lipidomic profiles of human skin tissues.
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Affiliation(s)
- Leetal Louie
- Porter School of Environment and Earth SciencesTel Aviv UniversityTel AvivIsrael
| | - Julia Wise
- Porter School of Environment and Earth SciencesTel Aviv UniversityTel AvivIsrael
| | - Ariel Berl
- Department of Plastic SurgeryMeir Medical CenterKfar SavaIsrael
| | - Ofir Shir‐az
- Department of Plastic SurgeryMeir Medical CenterKfar SavaIsrael
| | | | - Zohar Yakhini
- Arazi School of Computer ScienceReichman UniversityHerzliyaIsrael
- Department of Computer ScienceTechnion ‐ Israel Institute of TechnologyHaifaIsrael
| | - Avshalom Shalom
- Department of Plastic SurgeryMeir Medical CenterKfar SavaIsrael
| | - Alexander Golberg
- Porter School of Environment and Earth SciencesTel Aviv UniversityTel AvivIsrael
| | - Edward Vitkin
- Porter School of Environment and Earth SciencesTel Aviv UniversityTel AvivIsrael
- Arazi School of Computer ScienceReichman UniversityHerzliyaIsrael
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Austin E, Mineroff J, Dana I, Jagdeo J. Blue light aminolevulinic acid photodynamic therapy downregulates cell division and proliferation pathways in cutaneous squamous cell carcinoma. JOURNAL OF BIOPHOTONICS 2024; 17:e202300369. [PMID: 38332564 DOI: 10.1002/jbio.202300369] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Revised: 12/12/2023] [Accepted: 12/28/2023] [Indexed: 02/10/2024]
Abstract
5-Aminolevulinic acid (5-ALA) photodynamic therapy (PDT) is a treatment for actinic keratosis (AK) and has been studied as a treatment for noninvasive cutaneous squamous cell carcinoma (cSCC). PDT induces apoptosis and necrosis in AKs and cSCC. 5-ALA blue light PDT may modulate gene expression and pathways in surviving cells. In this study, differential gene expression and pathway analysis of cSCC and human dermal fibroblasts were compared before and after 5-ALA blue light PDT using RNA sequencing. No genes were differentially expressed after correcting for multiple testing (false discovery rate < 0.05). As a result, transcription factor, gene enrichment, and pathway analysis were performed with genes identified before multiple testing (p < 0.05). Pathways associated with proliferation and carcinogenesis were downregulated. These findings using 5-ALA blue light PDT are similar to previously published studies using methyl-aminolevulinic and red light protocols, indicating that surviving residual cells may undergo changes consistent with a less aggressive cancerous phenotype.
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Affiliation(s)
- Evan Austin
- Department of Dermatology, SUNY Downstate Medical Center, Brooklyn, New York, USA
- Department of Dermatology, VA New York Harbor Healthcare System, Brooklyn, New York, USA
| | - Jessica Mineroff
- Department of Dermatology, SUNY Downstate Medical Center, Brooklyn, New York, USA
- Department of Dermatology, VA New York Harbor Healthcare System, Brooklyn, New York, USA
| | - Isabella Dana
- Department of Dermatology, SUNY Downstate Medical Center, Brooklyn, New York, USA
- Department of Dermatology, VA New York Harbor Healthcare System, Brooklyn, New York, USA
| | - Jared Jagdeo
- Department of Dermatology, SUNY Downstate Medical Center, Brooklyn, New York, USA
- Department of Dermatology, VA New York Harbor Healthcare System, Brooklyn, New York, USA
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Korbecki J, Bosiacki M, Szatkowska I, Kupnicka P, Chlubek D, Baranowska-Bosiacka I. The Clinical Significance and Involvement in Molecular Cancer Processes of Chemokine CXCL1 in Selected Tumors. Int J Mol Sci 2024; 25:4365. [PMID: 38673949 PMCID: PMC11050300 DOI: 10.3390/ijms25084365] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 04/09/2024] [Accepted: 04/10/2024] [Indexed: 04/28/2024] Open
Abstract
Chemokines play a key role in cancer processes, with CXCL1 being a well-studied example. Due to the lack of a complete summary of CXCL1's role in cancer in the literature, in this study, we examine the significance of CXCL1 in various cancers such as bladder, glioblastoma, hemangioendothelioma, leukemias, Kaposi's sarcoma, lung, osteosarcoma, renal, and skin cancers (malignant melanoma, basal cell carcinoma, and squamous cell carcinoma), along with thyroid cancer. We focus on understanding how CXCL1 is involved in the cancer processes of these specific types of tumors. We look at how CXCL1 affects cancer cells, including their proliferation, migration, EMT, and metastasis. We also explore how CXCL1 influences other cells connected to tumors, like promoting angiogenesis, recruiting neutrophils, and affecting immune cell functions. Additionally, we discuss the clinical aspects by exploring how CXCL1 levels relate to cancer staging, lymph node metastasis, patient outcomes, chemoresistance, and radioresistance.
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Affiliation(s)
- Jan Korbecki
- Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, Powstańców Wlkp. 72, 70-111 Szczecin, Poland; (J.K.); (M.B.); (D.C.)
- Department of Anatomy and Histology, Collegium Medicum, University of Zielona Góra, Zyty 28, 65-046 Zielona Góra, Poland
| | - Mateusz Bosiacki
- Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, Powstańców Wlkp. 72, 70-111 Szczecin, Poland; (J.K.); (M.B.); (D.C.)
| | - Iwona Szatkowska
- Department of Ruminants Science, Faculty of Biotechnology and Animal Husbandry, West Pomeranian University of Technology, Klemensa Janickiego 29 St., 71-270 Szczecin, Poland;
| | - Patrycja Kupnicka
- Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, Powstańców Wlkp. 72, 70-111 Szczecin, Poland; (J.K.); (M.B.); (D.C.)
| | - Dariusz Chlubek
- Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, Powstańców Wlkp. 72, 70-111 Szczecin, Poland; (J.K.); (M.B.); (D.C.)
| | - Irena Baranowska-Bosiacka
- Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, Powstańców Wlkp. 72, 70-111 Szczecin, Poland; (J.K.); (M.B.); (D.C.)
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Brozek W, Clemens P, Ulmer H, Häring N, Concin H, Zitt E, Nagel G. Evaluation of a Population-Based Targeted Screening Approach for Skin Cancer with Long-Time Follow-Up in Austria including Potential Effects on Melanoma Mortality. Cancers (Basel) 2024; 16:1283. [PMID: 38610961 PMCID: PMC11011036 DOI: 10.3390/cancers16071283] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Revised: 03/19/2024] [Accepted: 03/22/2024] [Indexed: 04/14/2024] Open
Abstract
BACKGROUND whether screening for skin cancer affects melanoma-specific mortality in a population-based setting remains unclear. METHODS in this population-based cohort study, we characterized and evaluated a skin cancer prevention program following a targeted screening approach conducted in 1989-1994 in the Austrian province Vorarlberg, with follow-up until 2019. The general population and attendees of a health examination program served for comparison. RESULTS in the screening program including full follow-up until 2019, 207 invasive and 187 in situ melanomas were identified in 8997 individuals. Incidences of invasive and in situ melanomas were elevated compared to the general population (IRR 2.92, 95%-CI 2.49-3.41, and IRR 4.13, 95%-CI 3.53-4.83, respectively) and the health examination program (HR 3.02, 95%-CI 2.59-3.52, and HR 3.90, 95%-CI 3.30-4.61, respectively). Breslow thickness and Clark's level at time of invasive diagnosis were significantly lower in 1989-2019, but the tumor characteristics of the melanomas diagnosed during 1989-1994 did not differ from the comparison groups. Moreover, melanoma mortality was significantly elevated in the screening program (IRR 1.66, 95%-CI 1.00-2.75 vs. the general population, HR 2.12, 95%-CI 1.25-3.61 vs. the health examination cohort). Melanoma mortality in Vorarlberg declined until 2004, though statistically non-significantly. CONCLUSIONS given the uncertain effectiveness and high public expenditures of population-wide mass screening programs, primary prevention and targeted risk-based skin cancer screening might be promising alternatives.
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Affiliation(s)
- Wolfgang Brozek
- Agency for Preventive and Social Medicine, 6900 Bregenz, Austria; (P.C.); (H.U.); (H.C.); (E.Z.); (G.N.)
| | - Patrick Clemens
- Agency for Preventive and Social Medicine, 6900 Bregenz, Austria; (P.C.); (H.U.); (H.C.); (E.Z.); (G.N.)
- Department of Radio-Oncology, Feldkirch Academic Teaching Hospital, 6800 Feldkirch, Austria
| | - Hanno Ulmer
- Agency for Preventive and Social Medicine, 6900 Bregenz, Austria; (P.C.); (H.U.); (H.C.); (E.Z.); (G.N.)
- Department of Medical Statistics, Informatics and Health Economics, Innsbruck Medical University, 6020 Innsbruck, Austria
| | - Nina Häring
- Department of Dermatology and Venerology, Feldkirch Academic Teaching Hospital, 6800 Feldkirch, Austria;
| | - Hans Concin
- Agency for Preventive and Social Medicine, 6900 Bregenz, Austria; (P.C.); (H.U.); (H.C.); (E.Z.); (G.N.)
| | - Emanuel Zitt
- Agency for Preventive and Social Medicine, 6900 Bregenz, Austria; (P.C.); (H.U.); (H.C.); (E.Z.); (G.N.)
- Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), 6800 Feldkirch, Austria
- Department of Internal Medicine 3 (Nephrology, Dialysis and Hypertension), Feldkirch Academic Teaching Hospital, 6800 Feldkirch, Austria
| | - Gabriele Nagel
- Agency for Preventive and Social Medicine, 6900 Bregenz, Austria; (P.C.); (H.U.); (H.C.); (E.Z.); (G.N.)
- Institute of Epidemiology and Medical Biometry, Ulm University, 89081 Ulm, Germany
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Eggermont CJ, Hollestein LM, Hollatz A, Louwman M, Mooyaart AL, Nijsten T, Wakkee M. Cumulative incidence and timing of subsequent cutaneous squamous cell carcinomas stratified for patients with organ transplantation and hematologic malignancies: A nationwide cohort study. J Am Acad Dermatol 2024; 90:530-536. [PMID: 37871807 DOI: 10.1016/j.jaad.2023.10.036] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Revised: 10/01/2023] [Accepted: 10/16/2023] [Indexed: 10/25/2023]
Abstract
BACKGROUND There is lack of nationwide data on the cumulative incidence and timing of subsequent cutaneous squamous cell carcinomas (cSCCs) among patients with a first cSCC. OBJECTIVE To investigate the cumulative incidence and timing of subsequent cSCCs. METHODS Patients with a first cSCC in 2007/2008 from the Netherlands Cancer Registry were linked to the Netherlands Pathology Registry for subsequent cSCCs and the Netherlands Organ Transplant Registry. Cumulative incidence function curves were calculated for subsequent cSCCs and stratified for immune status. RESULTS Among the 12,345 patients, second to sixth cSCC occurred in 4325, 2010, 1138, 739, and 501 patients, with median time intervals of 1.4, 1.2, 0.9, 0.6, and 0.5 years after the previous cSCC, respectively. The cumulative incidence of a subsequent cSCC at 5 years increased from 28% to 67% for the second to sixth cSCC. For solid organ transplant recipients, the cumulative incidences increased from 74% to 92% and from 41% to 64% for patients with hematologic malignancy. LIMITATIONS Only histopathologically confirmed cSCCs were included. CONCLUSION The risk of a subsequent cSCC steeply rises with the number of prior cSCCs and immune status, while the time interval decreases. This can support more informed decisions about follow-up management.
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Affiliation(s)
- Celeste J Eggermont
- Department of Dermatology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, the Netherlands
| | - Loes M Hollestein
- Department of Dermatology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, the Netherlands; Department of Research and Development, Netherlands Comprehensive Cancer Organization (IKNL), Utrecht, the Netherlands
| | - Andrya Hollatz
- Department of Dermatology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, the Netherlands
| | - Marieke Louwman
- Department of Research and Development, Netherlands Comprehensive Cancer Organization (IKNL), Utrecht, the Netherlands
| | - Antien L Mooyaart
- Department of Pathology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, the Netherlands
| | - Tamar Nijsten
- Department of Dermatology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, the Netherlands
| | - Marlies Wakkee
- Department of Dermatology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, the Netherlands.
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Wunderlich K, Suppa M, Gandini S, Lipski J, White JM, Del Marmol V. Risk Factors and Innovations in Risk Assessment for Melanoma, Basal Cell Carcinoma, and Squamous Cell Carcinoma. Cancers (Basel) 2024; 16:1016. [PMID: 38473375 DOI: 10.3390/cancers16051016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Revised: 02/22/2024] [Accepted: 02/28/2024] [Indexed: 03/14/2024] Open
Abstract
Skin cancer is the most frequently diagnosed cancer globally and is preventable. Various risk factors contribute to different types of skin cancer, including melanoma, basal cell carcinoma, and squamous cell carcinoma. These risk factors encompass both extrinsic, such as UV exposure and behavioral components, and intrinsic factors, especially involving genetic predisposition. However, the specific risk factors vary among the skin cancer types, highlighting the importance of precise knowledge to facilitate appropriate early diagnosis and treatment for at-risk individuals. Better understanding of the individual risk factors has led to the development of risk scores, allowing the identification of individuals at particularly high risk. These advances contribute to improved prevention strategies, emphasizing the commitment to mitigating the impact of skin cancer.
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Affiliation(s)
- K Wunderlich
- Department of Dermatology, Hôpital Erasme, Université Libre de Bruxelles, 1070 Brussels, Belgium
| | - M Suppa
- Department of Dermatology, Hôpital Erasme, Université Libre de Bruxelles, 1070 Brussels, Belgium
- Department of Dermatology, Institute Jules Bordet, Université Libre de Bruxelles, 1070 Brussels, Belgium
| | - S Gandini
- Molecular and Pharmaco-Epidemiology Unit, Department of Experimental Oncology, European Institute of Oncology, IRCCS, 20139 Milan, Italy
| | - J Lipski
- Department of Dermatology, Hôpital Erasme, Université Libre de Bruxelles, 1070 Brussels, Belgium
| | - J M White
- Department of Dermatology, Hôpital Erasme, Université Libre de Bruxelles, 1070 Brussels, Belgium
| | - V Del Marmol
- Department of Dermatology, Hôpital Erasme, Université Libre de Bruxelles, 1070 Brussels, Belgium
- Department of Dermatology, Institute Jules Bordet, Université Libre de Bruxelles, 1070 Brussels, Belgium
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Wright QG, Sinha D, Wells JW, Frazer IH, Gonzalez Cruz JL, Leggatt GR. Peritumoral administration of immunomodulatory antibodies as a triple combination suppresses skin tumor growth without systemic toxicity. J Immunother Cancer 2024; 12:e007960. [PMID: 38296598 PMCID: PMC10831460 DOI: 10.1136/jitc-2023-007960] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/11/2024] [Indexed: 02/03/2024] Open
Abstract
BACKGROUND Skin cancers, particularly keratinocyte cancers, are the most commonly diagnosed tumors. Although surgery is often effective in early-stage disease, skin tumors are not always easily accessible, can reoccur and have the ability to metastasize. More recently, immunotherapies, including intravenously administered checkpoint inhibitors, have been shown to control some skin cancers, but with off-target toxicities when used in combination. Our study investigated whether peritumoral administration of an antibody combination targeting PD-1, 4-1BB (CD137) and VISTA might control skin tumors and lead to circulating antitumor immunity without off-target toxicity. METHODS The efficacy of combination immunotherapy administered peritumorally or intravenously was tested using transplantable tumor models injected into mouse ears (primary tumors) or subcutaneously in flank skin (secondary tumors). Changes to the tumor microenvironment were tracked using flow cytometry while tumor-specific, CD8 T cells were identified through enzyme-linked immunospot (ELISPOT) assays. Off-target toxicity of the combination immunotherapy was assessed via serum alanine aminotransferase ELISA and histological analysis of liver sections. RESULTS The data showed that local administration of antibody therapy eliminated syngeneic murine tumors transplanted in the ear skin at a lower dose than required intravenously, and without measured hepatic toxicity. Tumor elimination was dependent on CD8 T cells and was associated with an increased percentage of CD8 T cells expressing granzyme B, KLRG1 and Eomes, and a decreased population of CD4 T cells including CD4+FoxP3+ cells in the treated tumor microenvironment. Importantly, untreated, distal tumors regressed following antibody treatment of a primary tumor, and immune memory prevented growth of subcutaneous flank tumors administered 50 days after regression of a primary tumor. CONCLUSIONS Together, these data suggest that peritumoral immunotherapy for skin tumors offers advantages over conventional intravenous delivery, allowing antibody dose sparing, improved safety and inducing long-term systemic memory. Future clinical trials of immunotherapy for primary skin cancer should focus on peritumoral delivery of combinations of immune checkpoint antibodies.
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Affiliation(s)
- Quentin G Wright
- Frazer Institute, The University of Queensland, Brisbane, Queensland, Australia
| | - Debottam Sinha
- Frazer Institute, The University of Queensland, Brisbane, Queensland, Australia
| | - James W Wells
- Frazer Institute, The University of Queensland, Brisbane, Queensland, Australia
| | - Ian H Frazer
- Frazer Institute, The University of Queensland, Brisbane, Queensland, Australia
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Feng J, Zhang W, Zeng W, Dong X, Wang Y, Gu Y, Lan Y, Yang W, Lu H. Expression Analysis of Retinal G Protein-coupled Receptor and its Correlation with Regulation of the Balance between Proliferation and Aberrant Differentiation in Cutaneous Squamous Cell Carcinoma. Acta Derm Venereol 2024; 104:adv13213. [PMID: 38299232 PMCID: PMC10831868 DOI: 10.2340/actadv.v104.13213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Accepted: 10/03/2023] [Indexed: 02/02/2024] Open
Abstract
Retinal G protein-coupled receptor (RGR), a photosensitive protein, functions as a retinal photoisomerase under light conditions in humans. Cutaneous squamous cell carcinoma (cSCC) is linked to chronic ultraviolet exposure, which suggests that the photoreceptor RGR may be associated with tumorigenesis and progression of squamous cell carcinoma (SCC). However, the expression and function of RGR remain uncharacterized in SCC. This study analysed RGR expression in normal skin and in lesions of actinic keratosis, Bowen's disease and invasive SCC of the skin with respect to SCC initiation and development. A total of 237 samples (normal skin (n = 28), actinic keratosis (n = 42), Bowen's (n = 35) and invasive SCC (n = 132) lesions) were examined using immunohistochemistry. Invasive SCC samples had higher expression of RGR protein than the other samples. A high immunohistochemical score for RGR was associated with increased tumour size, tumour depth, Clark level, factor classification, and degree of differentiation and a more aggressive histological subtype. In addition, RGR expression was inversely correlated with involucrin expression and positively correlated with proliferating cell nuclear antigen (PCNA) and Ki67 expression. Furthermore, RGR regulates SCC cell differentiation through the PI3K-Akt signalling pathway, as determined using molecular biology approaches in vitro, suggesting that high expression of RGR is associated with aberrant proliferation and differentiation in SCC.
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Affiliation(s)
- Jianglong Feng
- 1. Department of Dermatology, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China; 2. School of Public Health, Guizhou Medical University, Guiyang, Guizhou, China ;3 .Department of Pathology, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
| | - Wei Zhang
- Department of Dermatology, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
| | - Wen Zeng
- Department of Dermatology, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
| | - Xian Dong
- Department of Dermatology, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
| | - Yu Wang
- Department of Dermatology, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
| | - Yangguang Gu
- Department of Dermatology, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
| | - Yinghua Lan
- Department of Dermatology, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
| | - Wenxiu Yang
- Department of Pathology, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
| | - Hongguang Lu
- Department of Dermatology, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China.
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Veeramani N, Jayaraman P, Krishankumar R, Ravichandran KS, Gandomi AH. DDCNN-F: double decker convolutional neural network 'F' feature fusion as a medical image classification framework. Sci Rep 2024; 14:676. [PMID: 38182607 PMCID: PMC10770172 DOI: 10.1038/s41598-023-49721-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Accepted: 12/11/2023] [Indexed: 01/07/2024] Open
Abstract
Melanoma is a severe skin cancer that involves abnormal cell development. This study aims to provide a new feature fusion framework for melanoma classification that includes a novel 'F' Flag feature for early detection. This novel 'F' indicator efficiently distinguishes benign skin lesions from malignant ones known as melanoma. The article proposes an architecture that is built in a Double Decker Convolutional Neural Network called DDCNN future fusion. The network's deck one, known as a Convolutional Neural Network (CNN), finds difficult-to-classify hairy images using a confidence factor termed the intra-class variance score. These hirsute image samples are combined to form a Baseline Separated Channel (BSC). By eliminating hair and using data augmentation techniques, the BSC is ready for analysis. The network's second deck trains the pre-processed BSC and generates bottleneck features. The bottleneck features are merged with features generated from the ABCDE clinical bio indicators to promote classification accuracy. Different types of classifiers are fed to the resulting hybrid fused features with the novel 'F' Flag feature. The proposed system was trained using the ISIC 2019 and ISIC 2020 datasets to assess its performance. The empirical findings expose that the DDCNN feature fusion strategy for exposing malignant melanoma achieved a specificity of 98.4%, accuracy of 93.75%, precision of 98.56%, and Area Under Curve (AUC) value of 0.98. This study proposes a novel approach that can accurately identify and diagnose fatal skin cancer and outperform other state-of-the-art techniques, which is attributed to the DDCNN 'F' Feature fusion framework. Also, this research ascertained improvements in several classifiers when utilising the 'F' indicator, resulting in the highest specificity of + 7.34%.
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Affiliation(s)
- Nirmala Veeramani
- School of Computing, SASTRA Deemed to Be University, Thanjavur, India
| | | | - Raghunathan Krishankumar
- Information Technology Systems and Analytics Area, Indian Institute of Management Bodh Gaya, Bodh Gaya, Bihar, 824234, India
| | | | - Amir H Gandomi
- Faculty of Engineering and Information Technology, University of Technology Sydney, Ultimo, NSW, Australia.
- University Research and Innovation Center (EKIK), Obuda University, Buddapest, Hungary.
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Tzenaki N, Xenou L, Goulielmaki E, Tsapara A, Voudouri I, Antoniou A, Valianatos G, Tzardi M, De Bree E, Berdiaki A, Makrigiannakis A, Papakonstanti EA. A combined opposite targeting of p110δ PI3K and RhoA abrogates skin cancer. Commun Biol 2024; 7:26. [PMID: 38182748 PMCID: PMC10770346 DOI: 10.1038/s42003-023-05639-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Accepted: 11/27/2023] [Indexed: 01/07/2024] Open
Abstract
Malignant melanoma is the most aggressive and deadly skin cancer with an increasing incidence worldwide whereas SCC is the second most common non-melanoma human skin cancer with limited treatment options. Here we show that the development and metastasis of melanoma and SCC cancers can be blocked by a combined opposite targeting of RhoA and p110δ PI3K. We found that a targeted induction of RhoA activity into tumours by deletion of p190RhoGAP-a potent inhibitor of RhoA GTPase-in tumour cells together with adoptive macrophages transfer from δD910A/D910A mice in mice bearing tumours with active RhoA abrogated growth progression of melanoma and SCC tumours. Τhe efficacy of this combined treatment is the same in tumours lacking activating mutations in BRAF and in tumours harbouring the most frequent BRAF(V600E) mutation. Furthermore, the efficiency of this combined treatment is associated with decreased ATX expression in tumour cells and tumour stroma bypassing a positive feedback expression of ATX induced by direct ATX pharmacological inactivation. Together, our findings highlight the importance of targeting cancer cells and macrophages for skin cancer therapy, emerge a reverse link between ATX and RhoA and illustrate the benefit of p110δ PI3K inhibition as a combinatorial regimen for the treatment of skin cancers.
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Affiliation(s)
- Niki Tzenaki
- Department of Biochemistry, School of Medicine, University of Crete, Heraklion, Greece
| | - Lydia Xenou
- Department of Biochemistry, School of Medicine, University of Crete, Heraklion, Greece
| | - Evangelia Goulielmaki
- Department of Biochemistry, School of Medicine, University of Crete, Heraklion, Greece
| | - Anna Tsapara
- Department of Biochemistry, School of Medicine, University of Crete, Heraklion, Greece
| | - Irene Voudouri
- Department of Biochemistry, School of Medicine, University of Crete, Heraklion, Greece
| | - Angelika Antoniou
- Department of Biochemistry, School of Medicine, University of Crete, Heraklion, Greece
| | - George Valianatos
- Department of Biochemistry, School of Medicine, University of Crete, Heraklion, Greece
| | - Maria Tzardi
- Department of Pathology, School of Medicine, University of Crete, University Hospital, Heraklion, Greece
| | - Eelco De Bree
- Department of Surgical Oncology, School of Medicine, University of Crete, University Hospital, Heraklion, Greece
| | - Aikaterini Berdiaki
- Department of Obstetrics and Gynaecology, School of Medicine, University of Crete, University Hospital, Heraklion, Greece
| | - Antonios Makrigiannakis
- Department of Obstetrics and Gynaecology, School of Medicine, University of Crete, University Hospital, Heraklion, Greece
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Yuan J, Li X, Yu S. Global, Regional, and National Incidence Trend Analysis of Malignant Skin Melanoma Between 1990 and 2019, and Projections Until 2034. Cancer Control 2024; 31:10732748241227340. [PMID: 38227397 DOI: 10.1177/10732748241227340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2024] Open
Abstract
BACKGROUND The goal of this study was to evaluate the global burden of malignant skin melanoma (MSM) from 1990 to 2019 using MSM-related data from the Global Burden of Disease study. METHODS The incidences' relationships with the social-demographic index (SDI) and human developmental index (HDI) were investigated. To determine significant changes in incidence trends, the joinpoint regression model was used. To demonstrate trends in MSM mortality rates, an Age-Period-Cohort framework was conducted. For the projection of new cases and the age-standardized incidence rate (ASR) of MSM incidence to 2034, the Nordpred method was used. RESULTS In 2019, the ASR incidence per 100, 000 people for MSM was 3.6 (95% UI, 2.6-4.2). MSM prevalence increased in most countries between 1990 and 2019 (average annual percentage change >0). HDI and annual percentage change (APC) (ρ = .63, P < .001), as well as SDI and ASR, had a positive correlation. The total MSM mortality rate declined globally, with an APC of -.61%. Likewise, the mortality rate for the age group of people with ages <77.5 years declined. Predictive analysis demonstrated a declining trend in ASR incidence and a growing number of MSM. CONCLUSION There are significant differences in ASR incidence among regions and countries. Despite decreases in ASR incidence and fatality, MSM remains one of the leading sources of cancer mortality and morbidity globally. MSM necessitates more primary prevention measures and screening in high-risk areas.
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Affiliation(s)
- Jin Yuan
- Department of Orthopedics, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Xiaoyang Li
- Department of Orthopedics, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Shengji Yu
- Department of Orthopedics, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
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Wang H, Guo C, Zhang X, Xu Y, Li Y, Wang T, Liu Z, Zhu X, Zhang T. Prognostic factors for competing risk in patients with AIDS-related Kaposi's sarcoma: A SEER population-based study. HIV Med 2024; 25:60-71. [PMID: 37574804 DOI: 10.1111/hiv.13530] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2023] [Accepted: 07/24/2023] [Indexed: 08/15/2023]
Abstract
OBJECTIVES Despite the improved survival of patients with AIDS and Kaposi's sarcoma (KS), competing events are a non-negligible issue affecting the survival of such patients. In this study, we explored the prognostic factors of KS-specific and non-KS-specific mortality in patients with AIDS-related KS (AIDS-KS), accounting for competing risk. METHODS We identified 17 103 patients with AIDS-KS aged 18-65 years between 1980 and 2016 from the Surveillance, Epidemiology, and End Results (SEER) 18 registry database. Prognostic factors for KS-specific and non-KS-specific mortality were determined by the Fine and Grey proportional subdistribution hazard model. We built competing risk nomograms and assessed their predictive performance based on the identified prognostic factors. RESULTS In total, 12 943 (75.68%) patients died, 1965 (15.50%) of whom died from competing events. The KS-specific mortality rate was 14 835 per 100 000 person-years, and the non-KS specific mortality rate was 2719 per 100 000 person-years. Specifically, age >44 years was associated with an 11% decrease in the subdistribution hazard of KS-specific mortality compared with age <43 years but a 50% increase in the subdistribution hazard of non-KS-specific mortality. Being male was associated with a 26% increase in the subdistribution hazard of KS-specific mortality compared with being female but a 32% decrease in the subdistribution hazard of non-KS-specific mortality. Notably, being in the antiretroviral therapy (ART) era consistently showed a decrease in the subdistribution hazard of both KS-specific and non-KS-specific mortality than being in the pre-ART era. CONCLUSIONS Competing events commonly occurred among patients with AIDS-KS, which deserves further attention to improve the prognosis of these patients.
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Affiliation(s)
- Haili Wang
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
| | - Chengnan Guo
- Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China
| | - Xin Zhang
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
| | - Yiyun Xu
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
| | - Yi Li
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
| | - Tianye Wang
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
| | - Zhenqiu Liu
- State Key Laboratory of Genetic Engineering, Human Phenome Institute, and School of Life Sciences, Fudan University, Shanghai, China
| | - Xiaohua Zhu
- Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China
| | - Tiejun Zhang
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
- Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China
- Yiwu Research Institue, Fudan University, Yiwu, China
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Passeron T, Lim HW, Goh CL, Kang HY, Ly F, Morita A, Ocampo-Candiani J, Puig S, Schalka S, Liu W, Demessant-Flavigny AL, Le Floc'h C, Kerob D, Dreno B, Krutmann J. Sun exposure behaviours as a compromise to paradoxical injunctions: Insight from a worldwide survey. J Eur Acad Dermatol Venereol 2023; 37:2481-2489. [PMID: 37590528 DOI: 10.1111/jdv.19421] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Accepted: 07/12/2023] [Indexed: 08/19/2023]
Abstract
BACKGROUND Behavioural interventions can improve attitudes towards sun protection but the impact remains inconsistent worldwide. OBJECTIVE To assess awareness of and attitudes towards the multiple facets of sun exposure and suggest ways to improve prevention from overexposure to the sun in all geographical zones and multiple skin types. METHODS Online survey was conducted from 28 September to 18 October 2021. Study population was selected from the Ipsos online Panel (3,540,000 panellists), aged ≥18 years, from 17 countries around the five continents. Demographics, sun-exposure habits and practices, understanding of risks and information on phototypes were documented and analysed using descriptive statistics. RESULTS Eighty-eight per cent of participants knew that sunlight can cause skin health problems (90% phototypes I-II, 82% phototypes V-VI, >90% in American and European countries, 72% in Asia and 85% in Africa). Eighty-five per cent used some form of protection against sunlight, predominantly: Seeking shade (77%), avoiding the midday sun (66%), facial application of sunscreen (60%) and wearing protective clothing (44%). The perception of sunlight itself is positive ('it gives energy' for 82%; 'tanned skin looks attractive' for 72%), although less in Asian countries and among individuals with dark skin phototypes. Eighty-three per cent reported having experienced sunburn, mainly in Australia, Canada, USA, Germany, France and Russia, and among individuals with dark skin phototypes. Only 12% systematically/often used all types of protection during exposure to the sun and 23% believed it is safe to go out in the sun with no protection when their skin is already tanned. From 13% (skin phototype I) to 26% (phototype VI) reported not using any form of protection against the sun. Knowledge and habits were significantly superior among people who are accustomed to seeing a dermatologist for a complete skin exam. CONCLUSIONS Dermatologists could play a crucial role in relaying novel prevention messages, more finely tailored to specific risks, populations and areas of the world.
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Affiliation(s)
- Thierry Passeron
- Department of Dermatology, Côte d'Azur University, Nice University Hospital Center, Nice, France
- INSERM U1065, C3M, Côte d'Azur University, Nice, France
| | - Henry W Lim
- Department of Dermatology, Henry Ford Health, Detroit, Michigan, USA
| | | | - Hee Young Kang
- Department of Dermatology, Ajou University School of Medicine, Suwon, South Korea
| | - Fatimata Ly
- Department of Dermatology, Cheikh Anta Diop Dakar University, EPS Institute of Social Hygiene, Dakar, Senegal
| | - Akimichi Morita
- Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Jorge Ocampo-Candiani
- Universidad Autonoma de Nuevo León, Facultad de Medicina, University Hospital "Dr. Jose E. González", Monterrey, Mexico
| | - Susana Puig
- Dermatology Department, Hospital Clinic de Barcelona, Barcelona University, Barcelona, Spain
| | - Sergio Schalka
- Medcin Skin Research Center and Biochemistry Department, Chemistry Institute of Sao Paulo University, Sao Paulo, Brazil
| | - Wei Liu
- Department of Dermatology, The General Hospital of Air Force PLA, Beijing, China
| | | | | | | | - Brigitte Dreno
- Nantes University, Univ Angers, INSERM, Immunology and New Concepts in ImmunoTherapy, INCIT, UMR 1302, Nantes, France
| | - Jean Krutmann
- IUF Leibniz Research Institute for Environmental Medicine, Duesseldorf, Germany
- Medical Faculty, Heinrich-Heine-University, Duesseldorf, Germany
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48
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Li C, Yan J, Wang P, Zhang H, Zeng Q, Zhang G, Wang X. 5-aminolevulinic acid sonodynamic therapy for cutaneous squamous cell carcinoma. Photodiagnosis Photodyn Ther 2023; 44:103801. [PMID: 37717674 DOI: 10.1016/j.pdpdt.2023.103801] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Revised: 09/06/2023] [Accepted: 09/08/2023] [Indexed: 09/19/2023]
Abstract
BACKGROUND The treatment of deep-invasive cutaneous squamous cell carcinoma (cSCC) is difficult. Sonodynamic therapy (SDT) has showed advantages in large penetration depth, small trauma, good repeatability, high targeting selectivity and effective protection for intact structure and function of tissues and organs. OBJECTIVE To study the efficacy and safety of 5-aminolevulinic acid SDT (ALA-SDT) in the treatment of cSCC. METHODS The absorption and transformation of ALA after co-incubation with cSCC were detected by UV-Vis and fluorescence absorption. The production of reactive oxygen species (ROS) when protoporphyrin IX (PpIX) excited with ultrasound was detected by ROS detection probe. Cytotoxicity of ALA-SDT to cSCC was detected with cytotoxicity indicators. The tumor volume changes and tumor weight of mice after ALA-SDT were detected. The effects of ALA-SDT on the growth of mice were evaluated through the changes in body weight of mice. Biosafety of treatment was further evaluated by histopathology to determine whether the tissues and organs of mice were affected after ALA-SDT. RESULTS ALA can be absorbed and converted into PpIX when incubated with cSCC cells and produces ROS with ultrasound irradiation. ALA-SDT showed a significant cytotoxicity on cSCC cells. With one session of ALA-SDT in vivo, tumor growth was slowed but not stopped and would proceed once treatment was ended. ALA-SDT had no significant effect on body weight changes and major tissues and organs of the mice. CONCLUSION ALA-SDT could safely and reduce cSCC cells growth both in vitro and in vivo.
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Affiliation(s)
- Chunxiao Li
- Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, China
| | - Jia Yan
- Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, China
| | - Peiru Wang
- Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, China
| | - Haiyan Zhang
- Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, China
| | - Qingyu Zeng
- Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, China
| | - Guolong Zhang
- Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, China
| | - Xiuli Wang
- Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, China.
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49
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Gupta N, Singh R, Seas A, Antwi P, Kaddumukasa MN, Kakooza Mwesige A, Kaddumukasa M, Haglund MM, Fuller AT, Koltai DC, Ukachukwu AEK. Epilepsy among the older population of sub-Saharan Africa: Analysis of the global burden of disease database. Epilepsy Behav 2023; 147:109402. [PMID: 37677904 DOI: 10.1016/j.yebeh.2023.109402] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Revised: 08/05/2023] [Accepted: 08/19/2023] [Indexed: 09/09/2023]
Abstract
INTRODUCTION Epilepsy is considered one of the most burdensome neurologic diseases by the World Health Organization due to the high risk of morbidity and mortality. Few studies have investigated the epidemiology of idiopathic epilepsy in Sub-Saharan Africa (SSA). This study aims to characterize the disease burden of epilepsy among the older population in SSA via a large international database. METHODS Descriptive epidemiological data from the Global Burden of Disease (GBD) database was collected for idiopathic epilepsy in all regions of SSA. The "older" population was defined as 55 years of age and above. The variables of interest included mortality, incidence, prevalence, and disability-adjusted life years (DALYs) rates per one hundred thousand populations. RESULTS The average mortality rate was highest in Western SSA (6.34 per 100,000), and all regions were significantly higher than the global average (p < 0.001). DALYs and incidence rates of idiopathic epilepsy in all regions of SSA were significantly higher than the global averages (p < 0.01). Globally, the older population had a significantly higher mortality rate than the younger population (2.78 vs 1.62, respectively; p < 0.01). The older population had a higher mortality rate than the younger population in each region of SSA (p < 0.01). Conversely, for DALYs, the younger population had a higher disease burden than the older population globally and in each region of SSA (p < 0.01). CONCLUSION This study is the first to examine the epidemiologic profile of idiopathic epilepsy in the older population in SSA. Our results indicate that, when compared with the global population, older adults in SSA suffer a greater disease burden and mortality. This study reports the immense need for increased resources and awareness regarding epilepsy in the elderly population of Africa.
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Affiliation(s)
- Nithin Gupta
- Duke Global Neurosurgery and Neurology, Duke University, Durham, NC, USA; Campbell School of Osteopathic Medicine, Lillington, NC, USA
| | - Rohin Singh
- Duke Global Neurosurgery and Neurology, Duke University, Durham, NC, USA; Department of Neurosurgery, University of Rochester, Rochester, NY, USA
| | - Andreas Seas
- Duke Global Neurosurgery and Neurology, Duke University, Durham, NC, USA; Duke University School of Medicine, Durham, NC, USA; Department of Biomedical Engineering, Duke University Pratt School of Engineering, Durham, NC, USA
| | - Prince Antwi
- Duke Global Neurosurgery and Neurology, Duke University, Durham, NC, USA; Department of Neurosurgery, Duke University, Durham, NC, USA; Duke Global Health Institute, Duke University, Durham, NC, USA
| | - Martin N Kaddumukasa
- Department of Medicine, Makerere University College of Health Sciences, and Mulago Hospital, Kampala, Uganda
| | - Angelina Kakooza Mwesige
- Department of Paediatrics & Child Health, Makerere University College of Health Sciences and Mulago Hospital, Kampala, Uganda; Astrid Lindgren Children's Hospital, Neuropediatric Research Unit, Karolinska Instituet, Sweden
| | - Mark Kaddumukasa
- Department of Medicine, Makerere University College of Health Sciences, and Mulago Hospital, Kampala, Uganda
| | - Michael M Haglund
- Duke Global Neurosurgery and Neurology, Duke University, Durham, NC, USA; Department of Neurosurgery, Duke University, Durham, NC, USA; Duke Global Health Institute, Duke University, Durham, NC, USA
| | - Anthony T Fuller
- Duke Global Neurosurgery and Neurology, Duke University, Durham, NC, USA; Department of Neurosurgery, Duke University, Durham, NC, USA; Duke Global Health Institute, Duke University, Durham, NC, USA
| | - Deborah C Koltai
- Duke Global Neurosurgery and Neurology, Duke University, Durham, NC, USA; Duke Global Health Institute, Duke University, Durham, NC, USA; Department of Neurology, Duke University, Durham, NC, USA; Department of Psychiatry & Behavioral Sciences, Duke University, Durham, NC, USA
| | - Alvan-Emeka K Ukachukwu
- Duke Global Neurosurgery and Neurology, Duke University, Durham, NC, USA; Department of Neurosurgery, Duke University, Durham, NC, USA.
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50
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Safi S, Ahmadzade M, Karimi S, Akbari ME, Rouientan H, Abolhosseini M, Rezaei Kanavi M, Khorrami Z. A registration trend in eyelid skin cancers and associated risk factors in Iran, 2005-2016. BMC Cancer 2023; 23:924. [PMID: 37777736 PMCID: PMC10543867 DOI: 10.1186/s12885-023-11414-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2023] [Accepted: 09/17/2023] [Indexed: 10/02/2023] Open
Abstract
BACKGROUND Eyelid skin cancers are the most prevalent ophthalmic malignancies. This study aimed to evaluate the association of the Human Development Index (HDI) and lifestyle risk factors with eyelid skin cancers in Iran. METHODS This ecological study analyzed the data collected from the Iranian National Population-based Cancer Registry (2005-2016). The data on provincial-level eyelid skin cancer risk factors were obtained from national sources. The association between provincial HDI and lifestyle risk factors with the prevalence of eyelid skin cancers was assessed. RESULTS The mean 12-year age-standardized incidence rate (ASIR) of eyelid skin cancers was 16.22 per 100,000 (9,104 cases). The overall ASIR showed an upward trend with an estimated annual average increase of 0.006 per year. There were positive correlations between the prevalence of overall eyelid skin cancers and provincial HDI, smoking, and obesity (r = 0.32, 0.42, and 0.37, respectively). In multivariate analysis, obesity/overweight remained a positive predictor for high prevalence of total eyelid skin cancers (OR = 1.97, 95%CI = 1.08-3.58, P = 0.026), carcinoma (2.10, 1.15-3.83, P = 0.015), and basal cell carcinoma (1.48, 0.99-2.20, P = 0.054). CONCLUSIONS An increasing trend in ASIR of eyelid skin cancers was observed in more than a decade in Iran which was positively associated with provincial HDI and prevalence of obesity. The findings of the study highlight the importance of promotional programs for preventing obesity/overweight and appropriate allocation of screening facilities based on the HDI level.
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Affiliation(s)
- Sare Safi
- Ophthalmic Epidemiology Research Center, Research Institute for Ophthalmology and Vision Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Department of Optometry, School of Rehabilitation, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohadese Ahmadzade
- Ophthalmic Research Center, Research Institute for Ophthalmology and Vision Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Saeed Karimi
- Ophthalmic Research Center, Research Institute for Ophthalmology and Vision Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Hamidreza Rouientan
- Ophthalmic Research Center, Research Institute for Ophthalmology and Vision Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Abolhosseini
- Ocular Tissue Engineering Research Center, Research Institute for Ophthalmology and Vision Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mozhgan Rezaei Kanavi
- Ocular Tissue Engineering Research Center, Research Institute for Ophthalmology and Vision Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Zahra Khorrami
- Ophthalmic Epidemiology Research Center, Research Institute for Ophthalmology and Vision Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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