Prevalence, Discontinuation Rate, and Risk Factors for Severe Local Site Reactions with Topical Field Treatment Options for Actinic Keratosis of the Face and Scalp.

Actinic keratoses (AKs) are common lesions on chronically sun damaged skin, which are morphologically characterized by lower third to full thickness atypia of epidermal keratinocytes. These lesions carry a risk of progression towards invasive squamous cell carcinoma (SCC); therefore, treatment of visible lesions and the field in case of field cancerization is recommended. Treatment of AK includes the destruction of atypical keratinocytes that clinically presents with various degrees of erythema, scaling, crusting, erosion, and other visible and subjective symptoms. Such inflammatory reactions may have an impact on the patient's social life and have shown to decrease compliance and adherence to therapy. Additionally, as various topical treatments have been proven to be effective in treating AK, tolerability of local site reactions (LSRs) might drive the decision for appropriate treatment in an individual scenario. Therefore, we aimed to review prevalence of severe LSRs among various topical treatments for AK. In addition, we summarized discontinuation rates due to LSRs and possible therapy-unrelated risk factors for the development of LSRs with increased severity.

Expression of p53, p63, p16, Ki67, Cyclin D, Bcl-2, and CD31 Markers in Actinic Keratosis, In Situ Squamous Cell Carcinoma and Normal Sun-Exposed Skin of Elderly Patients.

BACKGROUND: Age and cumulative exposure to ultraviolet (UV) light are primary contributors to skin cancer development. Regulatory proteins within the cell cycle are essential for the homeostasis of squamous epithelium. METHODS: This study assessed the expression of immunohistochemical markers p53, p63, p16, Ki67, Cyclin D, Bcl-2, and CD31 in keratinocyte intraepithelial neoplasia (actinic keratosis and squamous cell carcinoma in situ) compared to normal skin. The objective was to distinguish disease-specific changes from those attributable to ageing and sun exposure in elderly skin. RESULTS: Analysis included 22 actinic keratoses (AK), 7 in situ squamous cell carcinomas (SCC), and 8 normal skin biopsies. The mean age was 78.1 years for the AK/SCC group and 73.8 years for controls, with no significant age difference noted between the groups. The AK/SCC group exhibited a higher occurrence of amorphous masses, higher intensity of p53, lower Bcl-2 expression in the epidermis, higher Bcl-2 expression in the dermis, and higher CD31 expression in the dermis, all of which were statistically significant (p < 0.05). CONCLUSIONS: The study identifies distinct differences in the presence of amorphous masses and the expression levels of p53, Bcl-2, and CD31 between sun-exposed skin and in situ cutaneous squamous cell carcinomas, including actinic keratoses.

Clinical Characteristics of Actinic Keratosis Associated with the Risk of Progression to Invasive Squamous Cell Carcinoma: A Systematic Review.

BACKGROUND: Actinic keratosis (AK) is one of the most common lesions on chronically sun-damaged skin that has the risk of progression to invasive squamous cell carcinoma (SCC). With the possibilities of using digital technologies for following-up skin lesions and their increased use in the past few decades, our objective was to update the review by Quaedvlieg et al., 2006, and to review prospective studies from 2005 onwards to identify the clinical characteristics of AK that later progressed to SCC. METHODS: The PubMed, Scopus, and ScienceDirect databases were searched for relevant articles. The search had the following criteria: English language, human subjects and year from 2005 onwards. The study protocol was registered in the Prospero database with the record number CRD42020200429 and followed the PRISMA guidelines. The risk-of-bias assessment was performed using the QUIPS tool. RESULTS: From the 5361 studies screened, 105 reports were evaluated for eligibility, and 2 articles with 621 patients were included. The main AK types associated with the development of SCC were found to be baseline AK, also known as a long-standing AK, and merging AK, also called an "AK patch".

Stage IIA Skin Melanoma Treatment With ECHO-7 Oncolytic Virus Rigvir.

Melanoma is a global problem due to the rising numbers of skin melanoma cases. Current treatment guidelines for patients with stage IIA melanoma recommend only observation after surgery. In this report, the authors describe a patient with stage IIA skin melanoma treated with surgery and Rigvir virotherapy. Two years after the patient discovered a brown spot on the right cheek, surgery was indicated because the mass had started to ulcerate. Rigvir virotherapy was applied both before and after surgery. Observations made more than 7 years after surgery indicated no signs of disease progression. This case report illustrates an early treatment approach. Neoadjuvant treatment for early-stage melanoma is gaining more interest in both scientific and medical communities; therefore, the authors believe it is relevant to share their observations.

Correlation of Soluble CD44 Expression in Saliva and CD44 Protein in Oral Leukoplakia Tissues.

The aim of this study was to determine whether and how pan-CD44 protein expression in leukoplakia tissues correlates with positive SolCD44 test presence and their role in oral leukoplakia. SolCD44 and total protein expression in saliva were determined using an OncAlert® Oral Cancer Rapid test. Comparison of paired associations of total protein, SolCD44, mean number of CD44 expressed epithelial layers in leukoplakia tissue, and macrophages below the basement membrane between control group and patients with leukoplakia showed statistically significant results (p < 0.0001). It is shown that the total protein indicates low or elevated risk of possible malignant transformation processes in leukoplakia. Statistically significant differences between higher total protein level and clinical forms of oral leukoplakia (p < 0.0001), as well as CD44-labeled epithelial cell layer decrease (p < 0.0001), were found. This possibly points to the onset of the stemness loss in leukoplakia tissue. CD9 antigen expression in the exosomes of the oral epithelium explained the intercellular flow of SolCD44 and other fluids in the leukoplakia area. We conclude that the OncAlert® Oral Cancer Rapid test is a valuable screening method in daily clinical practice, in terms of complementing clinical diagnostics methods and to assess the potential for early malignancy.

Features associated with melanoma metastasis in Latvia.

Cutaneous melanoma (CM) is the most aggressive form of skin cancer, exhibits an increasing incidence worldwide and has a high potential to develop metastasis. The current study aimed to identify a set of parameters that may aid in predicting the probability and timing of the onset of CM metastasis. A retrospective analysis was performed using the archive data of 2,026 patients with CM that were treated at the Riga East University Hospital Latvian Oncology Centre, which is the largest oncological hospital in the country, between 1998 and 2015. A case-control study design was employed, where patients with metastasis (n=278) were used as the cases and patients without metastasis were used as the controls. The present study examined the associations between metastasis and potential risk factors and constructed multivariate models of features that predicted metastasis using stepwise regression. Time until metastasis was analyzed using negative binomial regression models. The results of the present study indicated an increase in the number of melanomas that developed metastases during 1998-2015. Tumor Breslow thickness was demonstrated to be significantly larger in patients with metastasis compared with those without (P=0.012). The presence of ulceration significantly increased the risk of metastases [odds ratio (OR), 1.66; 95% CI, 1.07-2.59; P=0.033]. The absence of pigment in melanoma tissues was indicated to lead to a greater likelihood of metastasis (OR, 2.14; 95% CI, 1.10-4.19; P=0.035). Shorter times from diagnosis until the onset of metastases were observed in older patients (incident rate ratio (IRR), 6.85; 95% CI, 2.43-19.30; P=2.78×10-4), and a borderline significant association was observed in those with ulcerated tumors (IRR, 1.33; 95% CI, 0.98-1.80; P=0.064). Therefore, the main features associated with the development of melanoma metastasis in Latvia were indicated to be tumor ulceration, absence of pigment and Breslow thickness.

5-aminolevulinic acid based photodynamic therapy for basal cell carcinoma: a 10-years follow-up study.

OBJECTIVE: This article presents long-term follow-up after use of topical photodynamic therapy (PDT) for basal cell carcinoma. PDT is treatment option for different tumors, involving use of specific agent which is activated by visible light and results in tissue destruction. MATERIALS AND METHODS: Overall 20 patients with 29 tumors were treated at the Latvian Oncology Center. Two illumination techniques were used: superficial for smaller lesions and multifiber contact for nodular tumors. Clinical outcome was evaluated at 1, 7, 44 months and 10 years after procedure. RESULTS: By 10 year follow up, there were 2 tumor recurrences and in one case there was tumor residual tissue after first PDT treatment. Overall after ten years follow-up complete response was 80% of cases. CONCLUSION: Data in this study supports hypothesis that PDT could be used for the treatment of non-invasive (superficial and nodular) basal cell carcinoma. Results in this study correspond with similar long-term follow-up studies.

Melanoma risk associated with MC1R gene variants in Latvia and the functional analysis of rare variants.

To evaluate the association of melanocortin 1 receptor gene (MC1R) variants with melanoma risk in a Latvian population, the MC1R gene was sequenced in 200 melanoma patients and 200 control persons. A functional study of previously uncharacterized, rare MC1R variants was also performed. In total, 26 different MC1R variants, including two novel variants Val165Ile and Val188Ile, were detected. The highest risk of melanoma was associated with the Arg151Cys variant (odds ratio (OR) 4.47, 95% confidence interval (CI) 2.19-9.14, P<0.001). A gene dosage effect was observed, with melanoma risk for carriers of two variants being twice (OR 3.98, 95% CI 2.15-7.38, P<0.001) that of carriers of one variant (OR 1.98, 95% CI 1.26-3.11, P=0.003). After stratification according to the pigmentation phenotype, the risk of melanoma remained in groups with otherwise protective phenotypes. Functional analyses of eight previously uncharacterized MC1R variants revealed that a subset of them is functionally relevant. Our results support the contribution of MC1R variants to a genetic predisposition to melanoma in Latvia.

Analysis of Latvian familial melanoma patients shows novel variants in the noncoding regions of CDKN2A and that the CDK4 mutation R24H is a founder mutation.

Hereditary cutaneous melanoma is associated with mutations in the high-risk CDKN2A gene in about 40% of melanoma-prone families. Mutations in the CDK4 gene are the cause in only a few pedigrees. In this study, we analyzed 20 Latvian familial melanoma probands and carried out a comprehensive analysis of CDKN2A including sequencing of its promoter/intronic regions and deletion screening. We also analyzed the critical second exon of the CDK4 gene. One novel intronic variant (IVS2+82C>T) of the CDKN2A gene and a small deletion (c.-20677_-20682delGTACGC) in its promoter region were found. Genotyping of the novel variants in larger melanoma and control groups indicated that the deletion increases the risk of melanoma (odds ratio=6.353, 95% confidence interval: 1.34-30.22, P=0.0168). The CDK4 gene analysis showed a Latvian melanoma family with the mutation R24H carried on the same haplotype as in two previously described Latvian CDK4-positive families. Our study suggests that the main risk gene in Latvian families with a strong family history of melanoma is CDK4 and that most of the other cases analyzed could be sporadic or associated with low-penetrance risk genes.

Quantity and quality analysis of dental prosthodontics among retirement age residents from nursing homes in different regions of Latvia and retirement age patients from dental clinic in Riga.

INTRODUCTION: The quality of life is closely related with condition of oral health, influence of subjective factors on the whole human body and patients perception of their oral health. In spite of the fact that the most part of Latvian retirement age residents use low-quality dentures and assess them satisfactory, these patients often have problems associated with quality of dentures. The aim of the present study was to evaluate oral health status, prosthodontics indicators and patients satisfaction with oral health among Latvian retirement age residents. PATIENTS AND METHODS: There were examined 465 retirement age volunteers (170 men and 295 women), 116 of them in dental clinic Sandent (Riga, 24.9% - control group), 137 (29.5%) in nursing homes in Zemgale and 212 (45.6%) in nursing homes in Kurzeme (Zemgale and Kurzeme are districts of Latvia). There were assessed quantity of prosthodontics among patients with partial defects of dental arches, there were estimated quality of dentures and patients satisfaction with existing prosthodontics. RESULTS: Oral health indicators among Latvian retirement age population are better than the same indicators among elderly residents of nursing homes. Among nursing homes residents with partial edentulousness in most of cases in oral cavities remained only few residual teeth which needed treatment. Removable and fixed dental prostheses used by nursing homes residents do not meet denture's quality criteria. Self-evaluation of dentures quality among retirement age residents of nursing homes is better and not correspond with existing dentures quality. CONCLUSIONS: In Latvia the quantity of prosthodontics in respect of partial removable dentures among the retired who regularly visit a dentist does not significantly differ from European retirement age population's dental prosthodontics quantity. Dental prosthodontics indicators of residents of nursing homes in Latvia are unsatisfactory (p<0.001). In retirement age population self-evaluation with quality of dentures is higher than actually existing.

Prognostic factors and epidemiological characteristics of cutaneous and mucosal head and neck melanoma.

OBJECTIVE. To describe the prognostic factors and epidemiological characteristics of cutaneous and mucosal head and neck melanoma and to identify the variables associated with mortality from this disease. MATERIAL AND METHODS. Patients treated for head and neck melanoma in the Oncology Centre of Latvia, Riga during a 10-year period were identified. Records from 124 cases were analyzed in a descriptive, retrospective study. For each patient, information regarding age, sex, tumor anatomic site, as well as ulceration, histological tumor subtypes, Breslow thickness and Clark invasion level was viewed. Disease specific survival rates were calculated. The frequencies of all study variables and their 95% confidence intervals were determined. Kaplan-Meier survival curves were produced to illustrate the survival differences for each variable. RESULTS. The patients' mean age was 67.36 years. The study included 81 females (65.32%) and 43 males (34.67%). The prevalent anatomical site for cutaneous head and neck melanoma was the cheek - 49% (n=55) and the intraocular site for mucosal melanoma (61.5%). A high percentage of thick cutaneous melanoma was detected. In 53 cases (47.3%) out of 112 cutaneous melanoma the tumor ulceration was found. Nodular melanoma subtype was predominating (38%). The incidence of cutaneous melanoma has increased unequally whereas mucosal melanoma of the head and neck is an uncommon cancer and the incidence rates in Latvia during a ten year period are decreasing. CONCLUSION. Female sex, advanced age, facial skin, tumor thickness, nodular subtype and ulceration carried a relevant risk of poor prognosis.

Evaluation of oral health status of retirement-age population in Latvia.

INTRODUCTION. Latvian government Health care financing regulations do not envisage free dental care in nursing homes. Consequently, in this situation arises need to carry out comparative evaluation of oral health status and quantity indicators of dental prosthodontics among retirement-age population in Latvia. The aim of the study was to estimate oral health and dental prosthodontics indicators among retirement-age population in Latvia. PATIENTS AND METHODS. We examinated 465 retirement-age inhabitants in Latvia. We assessed dental status, quantity and quality of the existing complete dental prostheses. We also evaluated the DMF-T index. RESULTS. Oral health indicators among Latvian retirement-age population are better than those for nursing homes residents in the same age group. Complete dental prostheses used by nursing homes residents do not meet denture's quality criteria. Retirement-age patients have oral hygiene problems. CONCLUSIONS. DMF-T index among Latvian retirement-age population is lower than among residents of nursing homes. The major component of DMF-T index is the number of lost teeth. The assessment of dental prostheses among residents of nursing homes showed unsatisfactory results. Retirement-age population in Latvia needs treatment of oral mucosal diseases, improvement of oral hygienic measures and increase of amount of dental prosthodontics.