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JMIR Dermatology Nov 2023Rosacea is a chronic inflammatory skin condition that predominantly manifests as facial flushing, irritation, and acne. Rosacea and cancer are thought to be linked by... (Review)
Review
BACKGROUND
Rosacea is a chronic inflammatory skin condition that predominantly manifests as facial flushing, irritation, and acne. Rosacea and cancer are thought to be linked by the commonality of inflammatory and immune response dysfunction. Studies that have looked into this possible association have reported mixed results.
OBJECTIVE
Given the conflicting literature on this topic, our study sought to evaluate the overall association between rosacea and several cancers commonly investigated in the literature.
METHODS
A systematic review was conducted using the Cochrane, PubMed, Embase, and Ovid databases. Studies were screened independently for inclusion of rosacea and glioma and breast, thyroid, hepatic, or skin cancers. Using information from the articles, rosacea and each cancer were categorized as having a positive, negative, or unclear association.
RESULTS
Our systematic review included 39 full-text studies that investigated the association between rosacea and various malignancies. Among the malignancies of concern, 41% (16/39) of the studies reported an association with basal cell carcinoma, with 2 cohorts revealing an adjusted risk ratio (RR) of 1.50 (95% CI 1.35-1.67) and 0.72 (95% CI 0.56-0.93). In total, 33% (13/39) of the studies reported an association with squamous cell carcinoma, with 2 cohorts revealing an adjusted RR of 1.4 (95% CI 1.02-1.93) and 1.30 (95% CI 0.90-1.88). A total of 8% (3/39) of the studies reported an association between breast cancer and melanoma, with breast cancer cohorts revealing an adjusted RR of 8.453 (95% CI 1.638-43.606), 1.03 (95% CI 0.89-1.20), and 1.36 (95% CI 1.18-1.58) and melanoma cohorts revealing an adjusted RR of 1.10 (95% CI 0.95-1.27), 0.63 (95% CI 0.47-0.85), and 0.96 (95% CI 0.57-1.62). A total of 5% (2/39) of the studies reported an association among nonmelanoma skin cancers, hepatic cancer, and thyroid carcinomas, with nonmelanoma skin cancer cohorts revealing an adjusted RR of 1.36 (95% CI 1.26-1.47) and 2.66 (95% CI 1.53-4.61), hepatic cancer cohorts revealing an adjusted RR of 1.42 (95% CI 1.06-1.90) and 1.32 (95% CI 0.89-1.95), and thyroid carcinoma cohorts revealing an adjusted RR of 1.06 (95% CI 0.68-1.65) and 1.59 (95% CI 1.07-2.36). Only 1 cohort reported an association with glioma, revealing an adjusted RR of 1.36 (95% CI 1.18-1.58). According to our review, patients with rosacea were statistically more likely to have nonmelanoma skin cancers, breast cancer, and glioma. Rosacea was not found to be substantially associated with melanoma. The associations between rosacea and hepatic and thyroid cancers were unclear because of conflicting results.
CONCLUSIONS
The current literature shows that rosacea is significantly associated with increased odds of nonmelanoma skin cancers, glioma, and breast cancer. Rosacea does not appear to be associated with melanoma. Further studies should be conducted to clarify the association between thyroid and hepatic cancers and rosacea.
PubMed: 37938876
DOI: 10.2196/47821 -
BMJ Evidence-based Medicine Jan 2024We aimed to systematically identify and scrutinise published empirical evidence about overdiagnosis in malignant melanoma and examine how frequent overdiagnosis of... (Review)
Review
OBJECTIVES
We aimed to systematically identify and scrutinise published empirical evidence about overdiagnosis in malignant melanoma and examine how frequent overdiagnosis of melanoma is and whether this is related to different types of interventions or diagnostic technologies.
DESIGN AND SETTING
Empirical studies that discussed overdiagnosis in malignant melanoma were eligible, including qualitative and quantitative studies in any type of population, age group and geographical location. We excluded studies that did not include empirical data, studies that only mentioned 'overdiagnosis' without addressing it further and studies that used the term overdiagnosis for cases of misdiagnosis or false positives.We developed the search strategy in cooperation with an information specialist. We searched five databases on 21 April 2022: MEDLINE, Embase, CINAHL, PsycINFO and Cochrane Library.This scoping review adheres to The JBI methodology and Prefered Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping reviews (PRISMA-ScR). Two reviewers independently screened titles, abstracts and full texts for inclusion and extracted data from the included studies. The data extracted include study characteristics, population details, research question, the context and the study's main results.
RESULTS
Our search resulted in 1134 potentially relevant studies. 35 studies were included: 29 register studies, 3 cohort studies, 1 case-control study, 1 survey study and 1 randomised controlled trial. Most register studies examined trends in melanoma incidence and/or mortality and found a significant increase in incidence between 0.39% and 6.6% annually and a little or no increase in mortality. Three cohort studies and one case-control study showed that skin screening was associated with increased detection of melanoma; especially in situ or thin invasive melanoma. Three studies estimated the degree of overdiagnosis which ranged from 29% to 60%.
CONCLUSIONS
Epidemiological data suggest a high degree of overdiagnosis in malignant melanoma. Studies that examined the association between skin screening and malignant melanoma all found increased detection of melanomas, mostly thin and in situ melanomas, which raises concern about overdiagnosis.
Topics: Humans; Melanoma; Case-Control Studies; Overdiagnosis; Skin Neoplasms; Diagnostic Errors
PubMed: 37793786
DOI: 10.1136/bmjebm-2023-112341 -
Cancers Jul 2023Sarcoma may show similarities to malignant melanoma in terms of morphologic and immunohistochemical aspects, making it difficult to differentiate between these two... (Review)
Review
BACKGROUND
Sarcoma may show similarities to malignant melanoma in terms of morphologic and immunohistochemical aspects, making it difficult to differentiate between these two neoplasms during the diagnostic process. This systematic review aims to summarize available evidence on cases of sarcoma that were initially diagnosed as melanoma.
METHODS
A comprehensive search of the MEDLINE/Pubmed, EMBASE, and SCOPUS databases was conducted through March 2023. We included case series and case reports of sarcoma patients that were initially diagnosed as malignant melanoma. PRISMA guidelines were followed.
RESULTS
Twenty-three case reports and four case series with a total of 34 patients were included. The clinical presentation was heterogeneous, and the most involved anatomical regions were lower limbs (24%), head/neck (24%), and upper limbs (21%). IHC positivity was reported for S100 (69%), HMB45 (63%), MelanA (31%), and MiTF (3%). The main reasons for a second assessment were unusual presentation (48%) and uncertain diagnosis (28%). EWSR1 translocation was investigated in 17/34 patients (50%) and found to be positive in 16/17 (94%). The final diagnosis was clear cell sarcoma (50%) or other soft tissue sarcomas (50%).
CONCLUSIONS
Melanoma and some histotypes of sarcoma share many similarities. In cases of atypical lesions, a second diagnosis should be considered, and ESWR1 translocation should be investigated.
PubMed: 37509250
DOI: 10.3390/cancers15143584 -
Molecular Genetics & Genomic Medicine Oct 2023The risk of skin cancer is determined by environmental factors like ultraviolet radiation (UVR), personal habits like time spent outdoors and genetic factors. This... (Review)
Review
BACKGROUND
The risk of skin cancer is determined by environmental factors like ultraviolet radiation (UVR), personal habits like time spent outdoors and genetic factors. This review aimed to survey existing studies in gene-environment (GxE) interaction on skin cancer risk, and report on GxE effect estimates.
METHODS
We searched Embase, Medline (Ovid) and Web of Science (Core Collection) and included only primary research that reported on GxE on the risk of the three most common types of skin cancer: basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and melanoma. Quality assessment followed the Newcastle-Ottawa Scale. Meta-analysis was not possible because no two studies examined the same interaction. This review was registered on PROSPERO (CRD42021238064).
RESULTS
In total 260 records were identified after exclusion of duplicates. Fifteen studies were included in the final synthesis-12 used candidate gene approach. We found some evidence of GxE interactions with sun exposure, notably, with MC1R, CAT and NOS1 genes in melanoma, HAL and IL23A in BCC and HAL and XRCC1 in SCC.
CONCLUSION
Sun exposure seems to interact with genes involved in pigmentation, oxidative stress and immunosuppression, indicating that excessive UV exposure might exhaust oxidative defence and repair systems differentially, dependent on genetic make-up. Further research is warranted to better understand skin cancer epidemiology and develop sun exposure recommendations. A genome-wide approach is recommended as it might uncover unknown disease pathways dependent on UV radiation.
PubMed: 37537768
DOI: 10.1002/mgg3.2259 -
Nutrients Dec 2023Nicotinamide is the active form of vitamin B3 (niacin) obtained through endogenous synthesis, mainly through tryptophan metabolism and dietary supplements, fish, meats,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Nicotinamide is the active form of vitamin B3 (niacin) obtained through endogenous synthesis, mainly through tryptophan metabolism and dietary supplements, fish, meats, grains, and dairy products. It participates in cellular energy metabolism and modulates multiple cellular survival and death pathways. Nicotinamide has been widely studied as a safe chemopreventive agent that reduces actinic keratosis (AKs) and non-melanoma skin cancers (NMSC).
METHODS
We used the Medline, EMBASE, PubMed, and Cochrane databases to search the concepts "nicotinamide", "chemoprevention", and "skin cancer" up to August 2023. Three independent authors screened titles and abstracts for intervention and study design before searching full texts for eligibility criteria. The primary outcome was the impact of oral nicotinamide on the incidence of NMSC in high-risk patients. We also conducted a systematic search to identify relevant epidemiological studies published evaluating dietary niacin intake and the risk of NMSC.
RESULTS
Two hundred and twenty-five studies were reviewed, and four met the inclusion criteria. There was no association between NAM consumption and risk for squamous cell carcinoma (SCC) (rate ratio (RR) 0.81, 95% CI 0.48-1.37; I = 0%), basal cell carcinoma (BCC) (RR 0.88, 95% CI 0.50-1.55; I = 63%), and NMSC (RR 0.82, 95% CI 0.61-1.12; I = 63%). Adverse events were rare and acceptable, allowing optimal compliance of patients to the treatment. We found only one article evaluating the association between niacin dietary intake and NMSC risk, supporting a potential beneficial role of niacin intake concerning SCC but not BCC or melanoma.
CONCLUSIONS
The present meta-analysis shows, by pooling immunocompetent and immunosuppressed patients, that there is insufficient evidence that oral nicotinamide therapy significantly reduces the number of keratinocyte cancers.
Topics: Animals; Humans; Niacinamide; Niacin; Chemoprevention; Skin Neoplasms; Carcinoma, Basal Cell; Carcinoma, Squamous Cell
PubMed: 38201930
DOI: 10.3390/nu16010100 -
Dermatology and Therapy Oct 2023The classical management of melanoma is surgery, but this can be challenging because of several factors, such as age, body area, lesion size, among others. Topical... (Review)
Review
INTRODUCTION
The classical management of melanoma is surgery, but this can be challenging because of several factors, such as age, body area, lesion size, among others. Topical imiquimod may be a therapeutic option for the treatment of melanoma in situ and lentigo maligna melanoma due to its efficacy, tolerability, and non-invasiveness. The purpose of this systematic review is to assemble current evidence on the treatment of non-metastatic melanoma with topical imiquimod.
METHODS
The PubMed/MEDLINE and Cochrane Library databases were searched as the primary sources using the main search terms "imiquimod" combined with "lentigo maligna" and "melanoma" with the command "AND." Articles were identified, screened, and extracted for relevant data, following the PRISMA guidelines.
RESULTS
A total of 87 studies covering 1803 lesions treated with imiquimod cream were identified and included in this sytematic review. Forty-nine studies were case reports, 16 were retrospective analyses, 3 were open label trials, six were case series; one study was a controlled randomized trial, one was a randomized trial, and one was a single-arm phase III trial. Because of the high number of low-evidence studies, the overall risk of bias resulted high. In 55 studies, imiquimod 5% was used in monotherapy as the primary treatment; only in one study was imiquimod 3.75% introduced. In most cases, the topical treatment was applied once daily, with the exception of nine cases where an increased daily dosage was prescribed. The total duration of the treatment regimen was extremely variable and depended on body area and tolerability, with differences among patients of the same study. In six studies, imiquimod was used as neoadjuvant therapy before the surgical excision, and in 11 studies it was used after surgery as complementary or adjuvant therapy. In total, 1133 of the 1803 (62.8%) lesions were reported to be cleared after the treatment, taking into account that not all of the patients completed the treatment. Of these 1133 lesions, histological clearance was achieved in 645 (56.9%) lesions and clinical clearance only was achieved in 490 (43.2%) lesions; relapse occurred in 107 lesions.
CONCLUSIONS
The heterogeneity of the studies included in this systematic review precludes the drawing of any relevant conclusions regarding the application of imiquimod. Its efficacy in melanoma in situ and lentigo maligna melanoma has been demonstrated, but further evidence from controlled studies concerning the modalities is missing.
PubMed: 37615838
DOI: 10.1007/s13555-023-00993-1 -
Autoimmunity Reviews Oct 2023Juvenile idiopathic inflammatory myopathies (JIIM) are a group of connective tissue disorders characterized by muscle inflammation and variable systemic involvement,... (Review)
Review
OBJECTIVE
Juvenile idiopathic inflammatory myopathies (JIIM) are a group of connective tissue disorders characterized by muscle inflammation and variable systemic involvement, including interstitial lung disease (ILD). Available data on JIIM-associated ILD are very limited. We performed a systematic review of the available clinical, laboratory, and radiological features of JIIM-associated ILD.
METHODS
A systematic literature review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.
RESULTS
A total of 90 patients were identified, of whom 77.8% had JDM, 10% amyopathic JDM, 7.8% anti-synthetase syndrome, 3.3% overlap syndrome, and 1.1% juvenile polymyositis. Anti-melanoma differentiation-associated gene 5 (MDA-5/CADM-140) was the most frequently reported myositis-specific antibody (32.2%). At diagnosis of ILD, 55.5% of patients had respiratory symptoms. Ground glass opacity was the most reported radiological feature (52.9%). Thirty-three % of patients developed rapidly progressive (RP) lung disease; 26.7% were admitted to the intensive care unit (ICU); 28.9% died; all deaths were due to ILD, with a median interval of 2 months (IQR 1.5-4.7) between the onset of respiratory symptoms and death. Patients admitted to the ICU and who died of ILD were more likely to be male, to have a rapidly progressive pattern, progression of radiological features, and a higher level of KL-6.
CONCLUSIONS
MDA-5/CADM-14 is associated with RP-ILD. ILD is a rare but severe manifestation among the spectrum of systemic involvement associated with JIIM, with a high rate of ICU admission and mortality. Early recognition and aggressive treatment are needed to prevent a severe outcome.
Topics: Humans; Male; Female; Dermatomyositis; Myositis; Polymyositis; Lung Diseases, Interstitial; Lung; Autoantibodies; Retrospective Studies
PubMed: 37611886
DOI: 10.1016/j.autrev.2023.103416 -
Cureus Dec 2023Crohn's disease (CD) presents a formidable challenge as a chronic inflammatory condition. This systematic review aimed to comprehensively assess upadacitinib, a novel... (Review)
Review
Crohn's disease (CD) presents a formidable challenge as a chronic inflammatory condition. This systematic review aimed to comprehensively assess upadacitinib, a novel Janus kinase (JAK) inhibitor, regarding its efficacy, safety, and mechanistic insights in CD treatment. A thorough search of electronic databases identified studies investigating upadacitinib's impact on CD patients. Study characteristics, efficacy outcomes (clinical remission and endoscopic response), safety profiles, and mechanistic insights were extracted and qualitatively synthesized. Methodological quality was assessed using established tools. The synthesis of three studies consistently demonstrated improvements in clinical remission rates and endoscopic outcomes in upadacitinib-treated patients. Adverse events, such as herpes zoster, intestinal perforation, non-melanoma skin cancer, adjudicated cardiovascular events, and anemia, were reported, necessitating vigilant safety monitoring. Upadacitinib emerges as a promising therapeutic option for CD, supported by its observed clinical benefits and mechanistic implications. However, safety concerns underscore the importance of careful patient selection. These findings contribute to the ongoing discussion surrounding personalized treatment approaches for CD, emphasizing the need for further research to confirm its enduring efficacy and safety.
PubMed: 38229787
DOI: 10.7759/cureus.50657 -
Cancers Jul 2023Despite a great success of immunotherapy in cancer treatment, a great number of patients will become resistant. This review summarizes recent reports on immune... (Review)
Review
Despite a great success of immunotherapy in cancer treatment, a great number of patients will become resistant. This review summarizes recent reports on immune checkpoint inhibitor retreatment or rechallenge in order to overcome primary resistance. The systematic review was performed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The search was performed using PubMed, Web of Science and Scopus. In total, 31 articles were included with a total of 812 patients. There were 16 retreatment studies and 13 rechallenge studies. We identified 15 studies in which at least one parameter (overall response rate or disease control rate) improved or was stable at secondary treatment. Interval treatment, primary response to and the cause of cessation for the first immune checkpoint inhibitors seem to be promising predictors of secondary response. However, high heterogeneity of investigated cohorts and lack of reporting guidelines are limiting factors for current in-depth analysis.
PubMed: 37444600
DOI: 10.3390/cancers15133490 -
Pharmacology & Therapeutics Apr 2024Melanoma is the most aggressive form of skin cancer, representing approximately 4% of all cutaneous neoplasms and accounting for up to 80% of deaths. Advanced stages of... (Review)
Review
Melanoma is the most aggressive form of skin cancer, representing approximately 4% of all cutaneous neoplasms and accounting for up to 80% of deaths. Advanced stages of melanoma involve metastatic processes and are associated with high mortality and morbidity, mainly due to the rapid dissemination and heterogeneous responses to current therapies, including immunotherapy. Immune checkpoint inhibitors (ICIs) are currently used in the treatment of metastatic melanoma (MM) and despite being linked to an increase in patient survival, a high percentage of them still do not benefit from it. Accordingly, the number of therapeutic regimens for MM patients using ICIs either alone or in combination with other therapies has increased, together with the need for reliable biomarkers that can both predict and monitor response to ICIs. In this context, circulating biomarkers, such as DNA, RNA, proteins, and cells, have emerged due to their ability to reflect disease status. Moreover, blood tests are minimally invasive and provide an attractive option to detect biomarkers, avoiding stressful medical procedures. This systematic review aims to evaluate the possibility of a non-invasive biomarker signature that can guide therapeutic decisions. The studies reported here offer valuable insight into how circulating biomarkers can have a role in personalized treatments for melanoma patients receiving ICIs therapy, emphasizing the need for rigorous clinical trials to confirm findings and establish standardized procedures.
Topics: Humans; Melanoma; Skin Neoplasms; Immunotherapy; Biomarkers
PubMed: 38367867
DOI: 10.1016/j.pharmthera.2024.108613