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Skin Research and Technology : Official... Jun 2024Research has previously established connections between the intestinal microbiome and the progression of some cancers. However, there is a noticeable gap in the...
OBJECTIVE
Research has previously established connections between the intestinal microbiome and the progression of some cancers. However, there is a noticeable gap in the literature in regard to using Mendelian randomisation (MR) to delve into potential causal relationships between the gut microbiota (GM) and basal cell carcinoma (BCC). Therefore, the purpose of our study was to use MR to explore the causal relationship between four kinds of GM (Bacteroides, Streptococcus, Proteobacteria and Lachnospiraceae) and BCC.
METHODS
We used genome-wide association study (GWAS) data and MR to explore the causal relationship between four kinds of GM and BCC. This study primarily employed the random effect inverse variance weighted (IVW) model for analysis, as complemented by additional methods including the simple mode, weighted median, weighted mode and MR‒Egger methods. We used heterogeneity and horizontal multiplicity to judge the reliability of each analysis. MR-PRESSO was mainly used to detect and correct outliers.
RESULTS
The random-effects IVW results showed that Bacteroides (OR = 0.936, 95% CI = 0.787-1.113, p = 0.455), Streptococcus (OR = 0.974, 95% CI = 0.875-1.083, p = 0.629), Proteobacteria (OR = 1.113, 95% CI = 0.977-1.267, p = 0.106) and Lachnospiraceae (OR = 1.027, 95% CI = 0.899-1.173, p = 0.688) had no genetic causal relationship with BCC. All analyses revealed no horizontal pleiotropy, heterogeneity or outliers.
CONCLUSION
We found that Bacteroides, Streptococcus, Proteobacteria and Lachnospiraceae do not increase the incidence of BCC at the genetic level, which provides new insight for the study of GM and BCC.
Topics: Humans; Mendelian Randomization Analysis; Carcinoma, Basal Cell; Gastrointestinal Microbiome; Skin Neoplasms; Genome-Wide Association Study; Streptococcus; Proteobacteria; Bacteroides; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide
PubMed: 38895789
DOI: 10.1111/srt.13804 -
Cancers Jun 2024To date, only a few population-representative studies have been carried out on the rare Merkel cell carcinoma (MCC). We provide incidence and survival estimates of MCC,...
BACKGROUND
To date, only a few population-representative studies have been carried out on the rare Merkel cell carcinoma (MCC). We provide incidence and survival estimates of MCC, including the conditional relative survival.
METHODS
We analyzed data from the cancer registry of North Rhine-Westphalia, Germany, 2008-2021, covering a population of 18 million. We included all newly diagnosed MCCs and calculated age-standardized (old European Standard population) incidence rates and unconditional and conditional relative survival.
RESULTS
Our analysis included 2164 MCC patients. The age-standardized incidence of MCC was 5.2 (men) and 3.8 (women) per million person-years. The 5-year relative survival was 58.8% (men) and 70.7% (women). Survival was lower among men than women in all age-sex groups and was highest for MCC of the upper extremity in both men (68.2%) and women (79.3%). The sex difference in survival is particularly due to the better survival of women with MCC of the head and neck. In terms of survival, the first two years are particularly critical.
CONCLUSIONS
Our data validate the worse survival among men and highlights a more favorable prognosis for MCCs located on the limbs. The first two years after diagnosis of MCC are the years with the highest excess mortality.
PubMed: 38893275
DOI: 10.3390/cancers16112158 -
Cancers Jun 2024Basal Cell Carcinoma (BCC) is the most common type of cancer among the white population. Individuals with fair skin have an average lifetime risk of around 30% for... (Review)
Review
Basal Cell Carcinoma (BCC) is the most common type of cancer among the white population. Individuals with fair skin have an average lifetime risk of around 30% for developing BCC, and there is a noticeable upward trend in its incidence rate. The principal treatment objectives for BCC involve achieving the total excision of the tumor while maximizing the preservation of function and cosmesis. Surgery is considered the treatment of choice for BCC for two main reasons: it allows for the highest cure rates and facilitates histological control of resection margins. However, in the subgroup of patients with low-risk recurrence or medical contraindications for surgery, new non-surgical treatment alternatives can provide an excellent oncological and cosmetic outcome. An evident and justified instance of these local therapies occurred during the COVID-19 pandemic, a period when surgical interventions carried out in hospital settings were not a viable option.
PubMed: 38893254
DOI: 10.3390/cancers16112135 -
Cancers May 2024Facial basal cell carcinoma (BCC) surgery enhances the quality of life (QoL) but leaves patients with inferior QoL, presumably caused by scarring, emphasizing the need...
Aesthetic Evaluation of Facial Scars in Patients Undergoing Surgery for Basal Cell Carcinoma: A Prospective Longitudinal Pilot Study and Validation of POSAS 2.0 in the Lithuanian Language.
Facial basal cell carcinoma (BCC) surgery enhances the quality of life (QoL) but leaves patients with inferior QoL, presumably caused by scarring, emphasizing the need to understand post-surgery aesthetic satisfaction. This study aimed to validate the Lithuanian version of the Patient and Observer Scar Assessment Scale (POSAS) 2.0 and utilise it to identify scar evaluation differences and correlations among POSAS scores and specific aesthetic facial regions, age, gender, surgery types, and short- and long-term QoL. Employing a prospective longitudinal design, 100 patients with facial scars after surgical BCC removal were enrolled. The validation phase confirmed the translated POSAS 2.0 psychometric properties, while the pilot phase used statistical analyses to compare scores among demographic and clinical groups and evaluate correlations between scar assessment and QoL. The findings indicate that the translated Lithuanian version of POSAS 2.0 exhibits good psychometric properties, revealing insights into aesthetic satisfaction with post-surgical facial scars and their impact on QoL. The Lithuanian version of the POSAS 2.0 was established as a valid instrument for measuring post-surgical linear scars. QoL with scar assessment statistically significantly correlates, 6 months after surgery, with worse scores, particularly notable among women, younger patients, and those with tumours in the cheek region.
PubMed: 38893210
DOI: 10.3390/cancers16112091 -
Cancers May 2024Skin cancers involve a significant concern in cancer therapy due to their association with various treatment modalities. This comprehensive review explores the increased... (Review)
Review
Skin cancers involve a significant concern in cancer therapy due to their association with various treatment modalities. This comprehensive review explores the increased risk of skin cancers linked to different anti-cancer treatments, including classic immunosuppressants such as methotrexate (MTX), chemotherapeutic agents such as fludarabine and hydroxyurea (HU), targeted therapies like ibrutinib and Janus Kinase inhibitors (JAKi), mitogen-activated protein kinase pathway (MAPKP) inhibitors, sonic hedgehog pathway (SHHP) inhibitors, and radiotherapy. MTX, a widely used immunosuppressant in different fields, is associated with basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and cutaneous melanoma (CM), particularly at higher dosages. Fludarabine, HU, and other chemotherapeutic agents increase the risk of non-melanoma skin cancers (NMSCs), including cSCC and BCC. Targeted therapies like ibrutinib and JAKi have been linked to an elevated incidence of NMSCs and CM. MAPKP inhibitors, particularly BRAF inhibitors like vemurafenib, are associated with the development of cSCCs and second primary melanomas (SPMs). SHHP inhibitors like vismodegib have been linked to the emergence of cSCCs following treatment for BCC. Additionally, radiotherapy carries carcinogenic risks, especially for BCCs, with increased risks, especially with younger age at the moment of exposure. Understanding these risks and implementing appropriate screening is crucial for effectively managing patients undergoing anti-cancer therapies.
PubMed: 38893081
DOI: 10.3390/cancers16111960 -
Cancers May 2024Cutaneous squamous cell carcinoma is a prevalent malignancy with a rising incidence and a notably high mutational load. Exploring the genetic nuances of cSCC and...
Cutaneous squamous cell carcinoma is a prevalent malignancy with a rising incidence and a notably high mutational load. Exploring the genetic nuances of cSCC and investigating molecular approaches stands as a potential avenue for improving outcomes in high-risk patients. This retrospective case-control study involved two cohorts, one of 14 patients (the "discovery cohort") and the other of 12 patients (the "validation cohort"), with cSCC located in the head/neck anatomical region and diagnosed at the pT2 stage. Overall, cases developed early local relapses of the disease, whereas controls never relapsed during the entire follow-up period. A next-generation sequencing (NGS) approach conducted on histological samples revealed that TP53 and CDKN2A were the most frequently mutated genes in our series. No specific mutations were identified as potential prognostic or therapeutic targets. Controls exhibited a tendency toward a higher mutational rate compared to cases. It is possible that an increased number of mutations could prompt the cSCC to expose more antigens, becoming more immunogenic and facilitating recognition by the immune system. This could enhance and sustain the immunological response, potentially preventing future recurrences.
PubMed: 38893077
DOI: 10.3390/cancers16111956 -
Journal of Clinical Medicine Jun 2024The rising incidence of Basal Cell Carcinoma (BCC), especially among individuals with significant sun exposure, underscores the need for effective and minimally...
The rising incidence of Basal Cell Carcinoma (BCC), especially among individuals with significant sun exposure, underscores the need for effective and minimally invasive treatment alternatives. Traditional surgical approaches, while effective, often result in notable cosmetic and functional limitations, particularly for lesions located on the face. This study explores High-Intensity Focused Ultrasound (HIFU) as a promising, non-invasive treatment option that aims to overcome these challenges, potentially revolutionizing BCC treatment by offering a balance between efficacy and cosmetic outcomes. Our investigation enrolled 8 patients, presenting a total of 15 BCC lesions, treated with a 20 MHz HIFU device. The selection of treatment parameters was precise, utilizing probe depths from 0.8 mm to 2.3 mm and energy settings ranging from 0.7 to 1.3 Joules (J) per pulse, determined by the lesion's infiltration depth as assessed via pre-procedure ultrasonography. A key component of our methodology included dermatoscopic monitoring, which allowed for detailed observation of the lesions' response to treatment over time. Patient-reported outcomes and satisfaction levels were systematically recorded, providing insights into the comparative advantages of HIFU. Initial responses after HIFU treatment included whitening and edema, indicative of successful lesion ablation. Early post-treatment observations revealed minimal discomfort and quick recovery, with crust formation resolving within two weeks for most lesions. Over a period of three to six months, patients reported significant improvement, with lesions becoming lighter and blending into the surrounding skin, demonstrating effective and aesthetically pleasing outcomes. Patient satisfaction surveys conducted six months post-treatment revealed high levels of satisfaction, with 75% of participants reporting very high satisfaction due to minimal scarring and the non-invasive nature of the procedure. No recurrences of BCC were noted, attesting to the efficacy of HIFU as a treatment option. The findings from this study confirm that based on dermoscopy analysis, HIFU is a highly effective and patient-preferred non-invasive treatment modality for Basal Cell Carcinoma. HIFU offers a promising alternative to traditional surgical and non-surgical treatments, reducing the cosmetic and functional repercussions associated with BCC management. Given its efficacy, safety, and favorable patient satisfaction scores, HIFU warrants further investigation and consideration for broader clinical application in the treatment of BCC, potentially setting a new standard in dermatologic oncology care. This work represents a pilot study that is the first to describe the use of HIFU in the treatment of BCC.
PubMed: 38892988
DOI: 10.3390/jcm13113277 -
Cells Jun 2024Basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) are high-incidence, non-melanoma skin cancers (NMSCs). The success of immune-targeted therapies in...
Basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) are high-incidence, non-melanoma skin cancers (NMSCs). The success of immune-targeted therapies in advanced NMSCs led us to anticipate that NMSCs harbored significant populations of tumor-infiltrating lymphocytes with potential anti-tumor activity. The main aim of this study was to characterize T cells infiltrating NMSCs. Flow cytometry and immunohistochemistry were used to assess, respectively, the proportions and densities of T cell subpopulations in BCCs (n = 118), SCCs (n = 33), and normal skin (NS, n = 30). CD8+ T cells, CD4+ T cell subsets, namely, Th1, Th2, Th17, Th9, and regulatory T cells (Tregs), CD8+ and CD4+ memory T cells, and γδ T cells were compared between NMSCs and NS samples. Remarkably, both BCCs and SCCs featured a significantly higher Th1/Th2 ratio (~four-fold) and an enrichment for Th17 cells. NMSCs also showed a significant enrichment for IFN-γ-producing CD8+T cells, and a depletion of γδ T cells. Using immunohistochemistry, NMSCs featured denser T cell infiltrates (CD4+, CD8+, and Tregs) than NS. Overall, these data favor a Th1-predominant response in BCCs and SCCs, providing support for immune-based treatments in NMSCs. Th17-mediated inflammation may play a role in the progression of NMSCs and thus become a potential therapeutic target in NMSCs.
Topics: Humans; Skin Neoplasms; Carcinoma, Squamous Cell; Th17 Cells; Lymphocytes, Tumor-Infiltrating; Th1 Cells; Carcinoma, Basal Cell; Female; Male; Aged; Cross-Sectional Studies; Middle Aged; CD8-Positive T-Lymphocytes; Aged, 80 and over; Adult
PubMed: 38891095
DOI: 10.3390/cells13110964 -
Journal of the American Academy of... Jun 2024Cemiplimab, a PD-1 inhibitor approved in 2018 for patients with locally advanced or metastatic cutaneous squamous cell carcinoma (cSCC) who are ineligible for curative...
Previous radiotherapy increases the efficacy of cemiplimab in the treatment of locally advanced and metastatic cutaneous squamous cell carcinoma: a retrospective analysis.
BACKGROUND
Cemiplimab, a PD-1 inhibitor approved in 2018 for patients with locally advanced or metastatic cutaneous squamous cell carcinoma (cSCC) who are ineligible for curative therapies, lacks clarity regarding the optimal patient selection despite its known efficacy.
OBJECTIVE
This retrospective study aims to assess the real-world treatment patterns and outcomes in patients with cSCC at our institution.
METHODS
A retrospective analysis of consecutively treated patients with cemiplimab for cSCC was conducted. Progression-Free Survival (PFS) and Overall Survival (OS) were evaluated alongside clinical-pathologic characteristics.
RESULTS
45 patients were included, of which 73.3% were male with a median age of 77 years. After 18 months of median follow-up median PFS and OS were not reached with a mean of 21.3 months ± 2.2 months and 25.3 ± 2.1 months, respectively. Univariate and multivariate analyses revealed significant correlations only between PFS and previous radiotherapy (p-values: 0.043 and 0.046, respectively).
LIMITATIONS
limitations include its retrospective nature, the low number of patients analyzed and the potential for inherent biases.
CONCLUSIONS
The study reveals a significant association between prior radiotherapy and improved PFS in cemiplimab-treated cSCC, suggesting the potential for combining radiotherapy with cemiplimab. Further exploration of this combined approach is warranted.
PubMed: 38885840
DOI: 10.1016/j.jaad.2024.06.023 -
JAAD Case Reports Jul 2024
PubMed: 38883170
DOI: 10.1016/j.jdcr.2024.04.025