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Background: Vismodegib is a first-in-class inhibitor of the hedgehog pathway for treatment of locally advanced basal cell carcinoma (laBCC) and metastatic BCC. Objectives: The purpose of this study is to report outcomes of patients with laBCC, with basal cell carcinoma nevus syndrome (Gorlin Goltz syndrome [G-G Syn]) treated with vismodegib in routine clinical practice in Slovenia in 8.3-year period. Methods: In this retrospective cohort study, we analyzed baseline characteristics, outcomes, and treatment-related adverse events from locally advanced BCC. The patients were divided into two cohorts: 39 laBCC or multiple BCC patients and 7 patients with G-G Syn who were treated with vismodegib from November 2012 till January 2021. Results: During 100-month period, 46 patients were diagnosed with laBCC (26), multiple BCC (13), and G-G Syn (7), all inappropriate for surgery or radiotherapy. Baseline characteristics: median age was 72.8 years in laBCC + multiple BCC cohort and 47.4 years in G-G Syn cohort. The objective response rate was 80% in laBCC + multiple BCC and 86% in G-G Syn cohort. Disease control rate (DCR) was 95% in laBCC + multiple BCC and 100% in G-G Syn cohort. Median duration of treatment was 9.9 months (range: 1.5–43.1) in laBCC and multiple BCC cohort and 19.5 months (range: 3.6–94.1) in G-G Syn cohort. Majority of treatment-emergent adverse events (TEAEs) in laBCC or multiple BCC cohort were grade 1 or 2 (96%), only 4% of AEs were grade 3. Majority of TEAEs in G-G Syn cohort were also grade 1 or 2 (87%), 13% of AEs were grade 3. No grade 4 or 5 vismodegib-related AEs were reported. Conclusion: Vismodegib has shown meaningful efficacy with DCR from 95% to 100% in patients with laBCC, multiple BCC, and G-G Syn in Slovenia. TEAEs were successfully alleviated with multidisciplinary approach and early supportive care.

Electrochemotherapy (ECT) is an effective locoregional therapy for cutaneous melanoma metastases and has been safely combined with immune checkpoint inhibitors in preliminary experiences. Since ECT is known to induce immunogenic cell death, its combination with immune checkpoint inhibitors might be beneficial. In this study, we aimed to investigate the effectiveness of ECT on cutaneous melanoma metastases in combination with pembrolizumab. We undertook a retrospective matched cohort analysis of stage IIIC%IV melanoma patients, included in the International Network for sharing practices of ECT (InspECT) and the Slovenian Cancer Registry. We compared the outcome of patients who received the following treatments: (a) pembrolizumab alone, (b) pembrolizumab plus ECT, and (c) ECT. The groups were matched for age, sex, performance status, and size of skin metastases. The local objective response rate (ORR) was higher in the pembrolizumab-ECT group than in the pembrolizumab group (78% and 39%, p < 0.001). The 1 year local progression-free survival (LPFS) rates were 86% and 51% (p < 0.001), and the 1 year systemic PFS rates were 64% and 39%, respectively (p = 0.034). The 1 year overall survival (OS) rates were 88% and 64%, respectively (p = 0.006). Our results suggest that skin-directed therapy with ECT improves superficial tumor control in melanoma patients treated with pembrolizumab. Interestingly, we observed longer PFS and OS in the pembrolizumab-ECT group than in the pembrolizumab group. These findings warrant prospective confirmation. Nasl. z nasl. zaslona. Opis vira z dne 31. 8. 2021. Bibliografija na koncu prispevka. Abstract.

Background. Acne is a very common dermatological condition, very few studies have been done regarding the knowledge, beliefs, and perceptions about the various treatment modalities and causative factors (nutrition, medication, cosmetics, pollutants, psychological and lifestyle factors and etc.) of acne. Methods. A quantitative written survey was performed. Survey sample – 451 young people 18-34 years old. Data analysis was performed using SPSS 26.0, calculated percentage frequencies, mean and standard deviation (SD), Pearson’s Chi Square test was used to detect statistically significant differences and correlation analysis was performed using the Spearman correlation. Results. The study shows that acne affects 49.9% of the surveyed young people. The prevalence of acne depends on the type of skin, tendency to have skin imperfections and genetic factors. Awareness and perception of skin care, factors affecting the occurrence of acne, and treatments used do not depend on the age of respondents. Conclusions. Young people lack professional knowledge of acne, skin care, and acne-provoking factors. They should take care of themselves, choose the right information from reliable sources and seek the help of specialists. Identifying the negative exogenous and endogenous factors and thus reducing their impact are mandatory for an adequate acne management.

ni abstrakta

ni abstrakta

ni abstrakta, Onkologija : strokovno-znanstveni časopis za zdravnike, Vol 22 No 2 (2018)

Karcinom Merklovih celic (KMC) je redek, agresiven nevroendokrini kožni rak s slabo prognozo, posebno, ko je v napredovalem stadiju. Incidenca na splošno narašča, čeprav podatki o incidenci kažejo na razlike med geografskimi področji. Med dejavnike tveganja štejemo starost, imunosupresijo in izpostavljenost ultravijoličnemu sevanju. Znana je povezava med MCC in okužbo s poliomavirusom, čeprav natančnega mehanizma, ki vodi v karcinogenezo, še ne razumemo v celoti. Pri lokalizirani bolezni je izbor zdravljenja kirurgija (ko je to mogoče), sledi mu dopolnilno obsevanje ali obsevanje v kombinaciji s kemoterapijo. Pri razsejani bolezni je bila doslej na voljo le kemoterapija, čeprav so dolgotrajni odgovori ob njej redki. Glede na to, da je onkogeneza tumorja povezana z integracijo poliomavirusa Merklovih celic in mutacijami, povzročenih z ultravijoličnim sevanjem, obstaja logična osnova za zdravljenje z imunoterapijo oz. protitelesi, ki ciljajo pot PD-L1/PD-1. Nedavno objavljene raziskave v prvem in drugem redu zdravljenja z inhibitorji imunskih stikal (anti-PD-1/PD-L1-protitelesi) kažejo obetajoče rezultate s sprejemljivim varnostnim profilom zdravljenja, zato tovrstno zdravljenje postaja standardno in je že priporočeno v mednarodnih smernicah za zdravljenje razsejanega raka Merklovih celic. Objavljeni podatki randomiziranih raziskav kažejo na obetajočo učinkovitost teh zdravil pri metastatski bolezni. Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine skin cancer with a poor prognosis in advanced stage. The incidence is increasing with some deviations between different geographic regions. The risk factors are advanced age, immunosuppression, and ultraviolet light exposure. There are associations between MCC and polyomavirus infection, but the exact mechanism that leads to carcinogenesis is yet to be fully understood. For localized disease (when feasible), surgery is the recommended treatment, followed by adjuvant radiation or chemoradiation. In the metastatic setting, chemotherapy has been the standard treatment, but durable responses are rare. As tumour oncogenesis is linked to Merkel cell polyomavirus integration and ultraviolet-radiation-induced mutations, there is rationale for treatment with immunotherapy antibodies that target the PD-L1/PD-1 pathway. However, recently published trials with immune checkpoint inhibitors in the first- and second-line showed promising results with a tolerable safety profile, and these are becoming the standard therapy, already included in international guidelines. The published data showed a high efficacy of avelumab in the metastatic setting.

Purpose Electrochemotherapy is increasingly entering into national and international guidelines, requiring formal evaluation of treatment costs and cost-effectiveness to ensure that its uptake provides value to budget-constrained health care systems. This study analyzed the early cost-effectiveness of electrochemotherapy in patients with Stage IIIc/IV skin melanoma in clinical practice in Slovenia. The costs of electrochemotherapy were compared to those of the standard of care, consisting of palliative treatment and therapy for symptoms. Methods wThe study enrolled 23 patients treated with electrochemotherapy at the Institute of Oncology (Ljubljana, Slovenia). The mean cost of electrochemotherapy was estimated using patient-specific cost data on electrochemotherapy procedures and subsequent follow-up. Quality-adjusted life-years (QALYs) were estimated by collecting EQ-5D-3L questionnaires at baseline, after complete or partial response following the treatment, and after a relapse of skin lesions. A discrete-time Markov model was built to estimate the lifetime costs and consequences of using electrochemotherapy compared to standard of care, from the perspective of the Slovenian health care system. The analysis was conducted separately in the whole patient sample and in the subset of patients with bleeding lesions. Deterministic and probabilistic sensitivity analyses were conducted to test model assumptions and to characterize the uncertainty around model parameters. Findings In the whole patient population, electrochemotherapy for skin melanoma Stage IIIc/IV was expected to increase QALYs by 0.29 (95% credible interval [CrI], 0.10–0.50), at the higher cost of 6568 EUR (95% CrI, 4593–8928) in comparison to the standard of care. At the cost-effectiveness threshold of 20,000 EUR/QALY, the estimated probabilities of electrochemotherapy being cost-effective compared to standard of care were 0.30 and 0.91 in the whole patient sample and in patients with bleeding lesions, respectively. In the whole sample population, a 50% reduction in the price of the electrodes was expected to increase the probability of electrochemotherapy being cost-effective from 0.30 to ~0.64. Implications The findings from this cost-effectiveness analysis of data from clinical practice were based on a small sample size (ie, 23 patents), which made the subgroup of patients with bleeding lesions very small. Therefore, the findings in this patient population should be carefully interpreted.

Malignant melanoma in Slovenia continues to increase rapidly in incidence over the last decades. Knowledge and risk factors amongst the population is still questionable and poorly investigated. Exposure to ultraviolet radiation is the leading risk factor for melanoma development, therefore physical protection and use of sunscreens with sun protection factors is crucial. The study aimed to investigate awareness of melanoma, risk factors and related behavior towards them among students of four faculties of University of Ljubljana: Faculty of Medicine, Faculty of Electrical Engineering, Faculty of Pharmacy and Faculty of Mathematics and Physics and to compare the answers between medical students and students of the other three faculties. The study was cross-sectional and survey-based. Students answered an anonymous questionnaire, which was sent to them through a website link. Answers obtained by 66.3% medical students and 33.7% students of other three faculties showed that medical students have statistically significant better knowledge about melanoma, (p=0.0001). It has also been found that there was statistical difference in frequency of protecting themselves from the sun (p=0.0001) and in used sun protection factor (p=0.015). Medical students with fair skin types more frequently used some means of protection from ultraviolet radiation, the measured difference was statistically significant (p=0.001). Medical students significantly better recognize malignant melanoma as the most threatening type of skin cancer. They also protect themselves from the sun more often and use higher sun protection factors. Slovenian adolescent population has high knowledge about harmful effects of exposure to ultraviolet radiation, but responds poorly to it., Onkologija, leto XXII, št. 1, junij 2018, Onkologija, Volume XXII, No. 1, June 2018

The incidence of melanoma is increasing, both in Slovenia and world-wide, more than any other form of cancer. According to the Cancer Registry of Slovenia, 415 patients were diagnosed with this disease in 2009 (1). Surgical removal of skin melanoma is the primary curative treatment for patients with early-stage disease. There are approximately 80% of such patients. In high-risk patients (around 10%), we also recommend treatment with high doses of interferon-α2b (2, 3). Metastatic melanoma is still an incurable disease with a 5-year survival of less than 5%. However, the prognosis for these patients has improved in the last few years, thanks to new developments in the field of systemic treatment. Besides standard treatment with systemic chemotherapy, new registered medicines are now also available with a different mechanism of action than chemotherapy, such as immunotherapy with the monoclonal antibody ipilimumab, BRAF inhibitors vemurafenib and dabrafenib, and MEK inhibitors (2, 3).

Background: Primary lymphoedema is a rare genetic disorder characterized by swelling of different parts of the body and highly heterogenic clinical presentation. Mutations in several causative genes characterize specific forms of the disease. FOXC2 mutations are associated with lymphoedema of lower extremities, usually distichiasis and late onset. Patients and methods: Subjects from three generations of a family with lymphoedema of lower limbs without distichiasis were searched for mutations in the FOXC2 gene. Results: All affected family members with lymphoedema of lower limbs without distichiasis, and still asymptomatic six years old girl from the same family, carried the same previously unreported insertion of adenosine (c.867insA) in FOXC2. Conclusions: Identification of a novel mutation in the FOXC2 gene in affected family members of three generations with lymphoedema of lower limbs without distichiasis, highlights the high phenotypic variability caused by FOXC2 mutations.

Koža je po površini največji, najtežji in po funkciji najbolj vsestranski organ našega telesa, ki varuje vse druge organe v našem organizmu, služi kot ščit pred vplivi okolja, regulira telesno temperaturo, ima čutilno funkcijo in še bi lahko naštevali. Na površini kože se lahko pojavijo tudi različne spremembe, ki so lahko nenevarne, ali pa gre za maligne novotvorbe. Zaradi tega je treba površino kože skrbno opazovati in jo pregledovati, da lahko ob vsaki spremembi obiščemo zdravnika, ki nam pove, kakšna je vrsta spremembe. V prvem, teoretičnem delu diplomskega dela so predstavljeni anatomija, fiziologija in patologija kože. Prav tako so predstavljene različne vrste kože, ter spreminjanja skozi različna življenjska obdobja. Ker imajo zunanji dejavniki velik vpliv tako na naše počutje, kot tudi na videz kože, so predstavljeni tudi dejavniki tveganja, ki negativno vplivajo na kožo in preventiva negativnih dejavnikov. V drugem, empiričnem delu diplomskega dela so predstavljeni rezultati raziskave, ki smo jo spomladi 2011 opravili v Zdravstvenem domu Mežica, v splošni ambulanti, med pacienti in pacientkami, ki so v tem času obiskali svojega osebnega splošnega zdravnika. Vprašalnik je bil sestavljen iz 30 vprašanj. Raziskati smo želeli, ali ženske bolje skrbijo za svojo kožo, kot moški, ali anketirani poznajo različne vrste kož in spreminjanje kože v različnih starostnih obdobjih, ter kako pogosto si odrasli pregledujejo kožo. Rezultati so pokazali, da je nekaj anketirancev osveščenih o spremembah na koži, o dejavnikih tveganja, ki vplivajo na kožo in o tem, kako se koža spreminja skozi starostna obdobja, vendar je še vedno več tistih, ki o tem ne vedo veliko, tistih, ki bi jih bilo potrebno poučiti o skrbi za kožo. Ženske bolje poznajo svojo kožo in bolje skrbijo zanjo, zato bi lahko svoje partnerje spodbujale in jim pomagale pri skrbi za kožo. Skin is the largest and the heaviest organ of our body which protects all other organs of our organism. According to its function it is the most complicated and the most versatile organ. It serves as a shield against environmental influences, regulates body temperature, has a sensory function, and many more. On the surface of the skin there may also appear different changes which may be benign or malignant neoplasms. It is necessary to carefully observe the skin’s surface, and if we notice a change, we have to visit a doctor, who defines a type of change. In the first part of the degree paper are anatomy, physiology and pathology of the skin are presented. Presentation is based on their type and change over the lifecycle. Since external factors and the appearance of the skin have a major impact on our mood, risk factors and prevention of negative factors are described. In the second part of the degree paper we present the results of the survey, which was done in spring 2011 in Health Center Mežica targeting adult people, who have visited their personal doctor that day. A questionnaire consists of thirty questions. Firstly, we wanted to explore if women take better care of their skin than man. Secondly, if adults know how many skin types we know and which changes we can find on skin. We wanted to explore how often adults examine their skin. The results show that some interviewed adults are aware of skin changes and risk factors, which negatively affect the skin. They are aware of its changes over the lifecycle, but we found out that there are many people, who are not aware of the importance of the skin and diseases which infect the skin. Those people should be educated. Women know their skin better and take better care of it, so they could encourage their partners in caring for the skin.

Interferon alfa se že mnogo let uspešno uporablja za zdravljenje kožnih T-celičnih limfomov in je za to bolezen še vedno nepogrešljivo zdravilo. Pri kožnih limfomih izkoriščamo predvsem njegovo antiproliferativno in imunomodulatorno delovanje. V sodobnih smernicah za zdravljenje kožnih T-celičnih limfomov je zdravilo izbire v stadijih IIB in III, kjer se pogosto uporablja v kombinaciji s sistemsko PUVA ali s sistemskim retinoidom. V monoterapiji se priporoča v stadijih IA do IIA, kadar so izčrpane lokalne možnosti zdravljenja. Kot vzdrževalno zdravljenje v manjših odmerkih pomembno podaljša remisijo. Režim zdravljenja prilagajamo individualno, glede na stadij bolezni, razširjenost kožnih sprememb in bolnikovo odzivnost na zdravilo. Zdravljenje je povezano z nekaterimi akutnimi in kroničnimi neželenimi sopojavi, ki so pogostejši pri večjih odmerkih, vendar so predvidljivi in praviloma reverzibilni. IFN-alpha has been used successfully for the treatment of cutaneous T-cell lymphoma for many years and it remains an indispensable drug for this condition. Its antiproliferative and immunomodulatory properties are used in the treatment of this disease. According to the current guidelines for the treatment of cutaneous T-cell lymphoma, it is considered as the first-line drug for stages IIB and III, where it is often administered concomitantly with systemic PUVA and retinoids. As monotherapy, it is recommended in stages IA and IIA, if skin directed therapies are not effective. As a maintenance therapy with low dosages, it is associated with prolongation of the duration of remissions. Optimal treatment regimen is adjusted individually, according to the stage of disease, dissemination of skin lesions and the patient’s tolerance for IFN. Several acute and chronic side effects can occur during the treatment with IFN-alpha, which are dose-related, predictable and often reversible.

Darbo tikslas. Ištirti apoptozę normalioje žmogaus odoje atliekant skaičia¬vimus visuose epidermio sluoksniuose. Metodika. TUNEL technika (angl. terminal deoxynucleotidyl transferase-mediated dUTP X nick end labeling) ištirtas 15-kos sveikų žmonių normalios odos epidermis. Apoptozinės ląstelės vertintos epidermio germinatyviniame ir diferencijuotame lygmenyse bei raginiame sluoksnyje. Skaičiuotos tik ryškiai TUNEL teigiamos ląstelės, turinčios būdingų morfologinių DNR fragmentacijos požymių. Rezultatai. Normalios odos gyvybingame epidermyje (be raginio) TUNEL teigiamų ląstelių koncentracija germinatyviniame lygmenyje 37,5 proc., diferencijuoto lygio grūdėtajame sluoksnyje – 41,7 proc. Išvados. Tyrimas parodė, kad apoptozė vyksta visuose normalios odos epidermio sluoks¬niuose. Taigi apoptozė labai svarbi ląstelių atsinaujinimui, formuojantis epidermio struktūrai visuose jo lygmenyse. The aim of the study was to investigate the apoptosis in normal human skin by examination of all epidermal layers. Material and methods. The normal skin epidermis of 15 healthy subjects was investigated by TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP-X nick end labeling) technique. Apoptotic cells were evaluated in the germinative and differential compartments and stratum corneum. Only highly TUNEL-positive cells with typical morphological DNA fragmentation signs were calculated. Results. In vital strata (except stratum corneum) of normal skin epidermis, 37.5% of all TUNEL-positive cells were observed in the germinative compartment and 41.7% in the granular layer of differential compartment. Conclusions. The study showed that apoptosis occurs in all layers of normal skin epidermis. It demonstrates that apoptosis is highly important in the renewal of cells and formation of epidermal structure within all compartments.

Photosensitive skin reactions occur when human skin reacts to ultraviolet radiation or visible light abnormally. The forms of photosensitivity are phototoxicity and photoallergy. Phototoxic disorders have a high incidence, whereas photoallergic reactions are much less frequent in human population. Several hundred substances, chemicals, or drugs may invoke phototoxic and photoallergic reactions. In order to avoid photosensitive reactions it is essential to determine the photosensitizing properties of such substances before drugs are introduced in therapy or products made available on the market. The article reviews the mechanisms of photosensitization, explains the most important differences between phototoxic and photoallergic reactions, summarizes the most common photosensitizers, and presents the clinical features and diagnostic procedures of phototoxic and photoallergic reactions.