Systemic Therapies for Advanced Basal Cell and Cutaneous Squamous Cell Carcinomas: Novel Targeted Therapies and Immunotherapies

Nonmelanoma skin cancers (NMSC), basal cell carcinoma (BCC), and cutaneous squamous cell carcinoma (cSCC) are the most common malignancies worldwide with a prevalence of epidemic proportions and continually rising global incidence rates, associated with increased morbidity rates and significant economic burden of their management. Although treatable cancers with low rates of metastasis and mortality, NMSCs reach an incurable state in small proportion of patients, becoming advanced, unresectable, or metastatic. Until recent years, patients with these conditions were considered for palliative radiotherapy and/or classical chemotherapies, which offer modest clinical benefit. Based on better understanding of the pathogenesis of these cancers, novel targeted therapies have been developed. We review novel systemic approaches for the treatment of aggressive forms of BCCs and cSCCs, with special emphasis on approved targeted molecular therapies and immunotherapie

Noninvasive Imaging Techniques for the Diagnosis of Nonmelanoma Skin Cancers

Nonmelanoma skin cancers (NMSC), basal cell carcinoma (BCC), and cutaneous squamous cell carcinoma (cSCC) are the most common neoplasms worldwide. Their incidence has been continually rising. This is due to several risk factors such as chronic sun exposure, longer life expectancy, sun-damaged skin, genetic predisposition, and immunosuppression. NMSCs are curable cancers if detected early and treated appropriately. Clinical examination is the first step towards their diagnosis, with accuracy depending on clinician expertise. Dermoscopy has become an irreplaceable diagnostic procedure for clinical examination and improving diagnostic accuracy of skin cancers. However, skin biopsy with histopathological analysis remains the gold standard in establishing a definite diagnosis. Repeated biopsies, however, are not acceptable in patients with multiple suspicious lesions and are often redundant in cases of lesions that are challenging to identify, as they are often benign. Several medical imaging technologies are available as additional tools for noninvasive examination of NMSCs and include reflectance confocal microscopy (RCM), high-frequency ultrasound (HFUS), optical coherence tomography (OCT), Raman spectroscopy, fluorescence polarization, and others. These methods enable clinicians to establish more rapid and accurate diagnoses without the need for invasive biopsies and to achieve optimal treatment for NMSC. RCM an HFUS are discussed along with their clinical applications

Noninvasive Imaging Techniques for the Diagnosis of Nonmelanoma Skin Cancers

Nonmelanoma skin cancers (NMSC), basal cell carcinoma (BCC), and cutaneous squamous cell carcinoma (cSCC) are the most common neoplasms worldwide. Their incidence has been continually rising. This is due to several risk factors such as chronic sun exposure, longer life expectancy, sun-damaged skin, genetic predisposition, and immunosuppression. NMSCs are curable cancers if detected early and treated appropriately. Clinical examination is the first step towards their diagnosis, with accuracy depending on clinician expertise. Dermoscopy has become an irreplaceable diagnostic procedure for clinical examination and improving diagnostic accuracy of skin cancers. However, skin biopsy with histopathological analysis remains the gold standard in establishing a definite diagnosis. Repeated biopsies, however, are not acceptable in patients with multiple suspicious lesions and are often redundant in cases of lesions that are challenging to identify, as they are often benign. Several medical imaging technologies are available as additional tools for noninvasive examination of NMSCs and include reflectance confocal microscopy (RCM), high-frequency ultrasound (HFUS), optical coherence tomography (OCT), Raman spectroscopy, fluorescence polarization, and others. These methods enable clinicians to establish more rapid and accurate diagnoses without the need for invasive biopsies and to achieve optimal treatment for NMSC. RCM an HFUS are discussed along with their clinical applications

Systemic Therapies for Advanced Basal Cell and Cutaneous Squamous Cell Carcinomas: Novel Targeted Therapies and Immunotherapies

Nonmelanoma skin cancers (NMSC), basal cell carcinoma (BCC), and cutaneous squamous cell carcinoma (cSCC) are the most common malignancies worldwide with a prevalence of epidemic proportions and continually rising global incidence rates, associated with increased morbidity rates and significant economic burden of their management. Although treatable cancers with low rates of metastasis and mortality, NMSCs reach an incurable state in small proportion of patients, becoming advanced, unresectable, or metastatic. Until recent years, patients with these conditions were considered for palliative radiotherapy and/or classical chemotherapies, which offer modest clinical benefit. Based on better understanding of the pathogenesis of these cancers, novel targeted therapies have been developed. We review novel systemic approaches for the treatment of aggressive forms of BCCs and cSCCs, with special emphasis on approved targeted molecular therapies and immunotherapies

Mogu li se na koži odraziti malignomi unutarnjih organa? Dokazi iz kliničkih slučajeva

Although there are many single case reports on paraneoplastic dermatoses in the literature, there are very rare articles containing multiple cases. A retrospective study was performed to examine paraneoplastic dermatoses and accompanying malignancies based on skin manifestations and appropriate diagnostic evaluations. We recorded outcomes, current conditions, and surgical/oncologic treatments. Analysis revealed paraneoplastic dermatoses in 17 patients with various skin lesions, i.e. eczematous dermatitis, vasculitis, subacute cutaneous lupus erythematosus, pruritus, chronic urticaria/ angioedema, alopecia areata, flushing, bullous pemphigoid, dermatomyositis, and localized scleroderma (morphea). They were associated with different solid and hematologic malignancies (3 gastric, 2 prostate, 2 bladder, 2 thyroid, and 2 lymphoma), along with 1 case each of the following: lung, hepatocellular, esophageal, endometrial, kidney, and multiple myeloma. The majority of skin lesions gradually regressed after malignancy treatment. To our knowledge, our three cases of paraneoplastic eczematous dermatitis are the first to be associated with gastric, prostate and endometrial cancer. Additionally, we report a case of a patient with alopecia areata of the beard associated with thyroid cancer. Early malignancy detection based on skin markers makes early introduction of surgical/oncologic therapy possible and usually leads to skin lesion regression while reducing revolving door visits to specialists and the (financial) burden on the healthcare system.Iako postoje mnogi pojedinačni prikazi slučajeva paraneoplastičnih dermatoza u literaturi, vrlo je malo radova koji prikazuju mnogobrojne slučajeve. Provedena je retrospektivna studija kojom smo istražili kožne promjene i provedenu dijagnostiku radi dokaza paraneoplastičnih dermatoza i s njima povezanih zloćudnih bolesti. Pritom smo uzeli u obzir dijagnostičko- terapijske rezultate, postojeće manifestacije i provođenje kirurško-onkološke terapije. Analizom smo paraneoplastične dermatoze utvrdili kod 17 bolesnika s različitim kožnim promjenama: ekcematoidnim dermatitisom, vaskulitisom, subakutnim kožnim eritematoznim lupusom, pruritusom, kroničnom urtikarijom/angioedemom, alopecijom areatom, crvenilom, buloznim pemfigoidom, dermatomiozitisom i lokaliziranom sklerodermijom (morfeom). One su bile povezane s različitim malignomima unutarnjih organa i hematološkim malignomima (zabilježena su 3 karcinoma želuca, 2 karcinoma prostate, 2 karcinoma mokraćnog mjehura, 2 karcinoma štitnjače i 2 limfoma te po jedan slučaj karcinoma pluća, jetre, endometrija, bubrega i multipli mijelom). Većina kožnih promjena se postupno povukla nakon odgovarajućeg liječenja zloćudne bolesti. Prema našim saznanjima, naša tri slučaja paraneoplastičnog ekcematoidnog dermatitisa su prvi slučajevi te bolesti povezane s karcinomima želuca, prostate i endometrija. Također smo prikazali i slučaj bolesnika s alopecijom areatom brade koji je bio povezan s karcinomom štitne žlijezde. Rano otkrivanje malignih bolesti pomoću praćenja kožnih promjena vodi do pravodobne kirurško/onkološke terapije i moguće regresije kožnih promjena. Time se ujedno smanjuje lutanje bolesnika kod raznih specijalista i sveukupni trošak zdravstvenog sustava

Utilization of somatic healthcare in Croatian patients with schizophrenia spectrum disorder, major depression, PTSD and the general population

Background: Utilization of somatic healthcare services is highly predictive of the development of chronic physical illnesses and increased mortality risks. The objective of this study was to assess the differences in healthcare utilization among patients with schizophrenia spectrum disorders (SSD), major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) and the general population in Croatia. ----- Methods: We enrolled 566 Croatian participants from the general population, 282 with SSD, 178 with MDD, and 86 with PTSD. The primary outcome was a self-reported specialist consultation for non-psychiatric (e.g., somatic) causes within the previous 12 months. ----- Results: Although SSD patients with chronic physical illnesses were significantly more often hospitalized for physical illness than the general population, the proportion of patients who had a specialist consultation were equal in SSD and the general population. MDD and PTSD patients had significantly higher adjusted odds for specialist consultation than the general population and SSD patients (MDD compared to SSD: OR = 2.14; 95% CI 1.27–3.59; PTSD compared to SSD: OR = 2.03; 95% CI 1.00–4.10). ----- Conclusions: SSD patients’ utilization of somatic healthcare is equal to the general population, despite their increased healthcare needs. However, their utilization is lower than in MDD and PTSD patients and, therefore, probably not adequate

Diagnosis and treatment of nonmelanoma skin cancer

Bazocelularni karcinomi (BCC) i planocelularni karcinomi kože (SCC), zajedničkog naziva nemelanomski zloćudni tumori kože (NMSC), danas su najčešći zloćudni tumori u bijeloj populaciji u većine zemalja svijeta. Uzroke povećane incidencije nalazimo u djelovanju nekoliko čimbenika rizika od kojih su najvažniji povećana izloženost suncu, duže trajanje života i genetska predispozicija. Obrada bolesnika s tumorskim tvorbama suspektnim na NMSC započinje uzimanjem anamneze i fizikalnim pregledom kože. Jedna od najčešće korištenih neinvazivnih dijagnostičkih tehnika je dermatoskopija. Pregled uzorka kože dobivenog biopsijom smatra se zlatnim standardom u dijagnostici NMSC-a. Među novim dijagnostičkim tehnikama vrlo uspješnom se pokazala refleksijska konfokalna mikroskopija (RCM). Terapija NMSC-a je kirurška i nekirurška. Za veliku većinu NMSC-a, kirurške metode predstavljaju kurativni tretman jer su najbolji način odstranjenja tumora u cijelosti. Pri tom se uz standardnu eksciziju kao zlatni standard, koriste Mohsova mikrografska kirurgija (MMS) i ablativne metode. Nekirurške metode liječenja terapija su izbora za određene bolesnike te se u mnogim slučajevima stope izlječenja približavaju onima postignutima kirurgijom, a prednosti su niži troškovi liječenja te kozmetički prihvatljiviji ishod. U ove oblike liječenja ubrajamo fotodinamičku terapiju (PDT), topički 5-fluorouracil (5-FU), topičku terapiju imikvimodom, intralezijski interferon alfa-2b (IFN-α2b), radijacijsku terapiju i kemoterapiju. Nove molekularne terapije usmjerene protiv Hedgehog (Hh) signalnog puta, kao što su vismodegib i sonidegib, predstavljaju učinkovit terapijski tretman za lokalno uznapredovale/ neoperabilne BCC (laBCC) i metastaske BCC (mBCC).Basal cell carcinomas (BCC) and squamous cell carcinomas (SCC), together referred to as nonmelanoma skin cancer (NMSC), are the most commonly diagnosed malignant neoplasms in the Caucasians in most countries around the world. Causes of this condition may be found in few risk factors such as increased exposure to sunlight, longer life expectancy and genetic predisposition. Workup of patients with lesions suspicious of NMSC should begin with a history and physical examination of the skin. Dermoscopy is one of the most commonly used noninvasive diagnostic techniques. The evaluation of a sample obtained by skin biopsy is considered as the gold standard in the diagnosis of NMSC. Among novel diagnostic techniques, reflectance confocal microscopy (RCM) showed great success. Therapy of NMSCs includes surgical and nonsurgical techniques. For the vast majority of NMSCs, surgery is the curative treatment of choice as it provides the best means of controlling that the entire tumor is removed. Besides excisional surgery as gold standard, Mohs' micrographic surgery (MMS) and ablative methods can also be used. Nonsurgical methods represent a therapy option for certain patients as in many cases cure rates approach those provided by surgery, and other advantages are lower overall costs and more cosmetically acceptable outcomes. These methods include photodynamic therapy (PDT), topical 5-fluorouracil (5-FU), imiquimod therapy, intralesional interferon alfa-2b (IFN-α2b), radiotherapy and chemotherapy. Novel molecular therapies targeted against Hedgehog (Hh) signaling pathway, such as vismodegib and sonidegib, represent powerful treatment options for locally advanced/ inoperable BCCs (laBCCs) and metastatic BCCs (mBCCs)

Gut Microbiome Composition in Patients with Chronic Urticaria: A Review of Current Evidence and Data

Recent studies have linked gut microorganism composition and chronic urticaria (CU); however, the underlying mechanisms responsible for this connection are unknown. Since the human immune system is in homeostasis with microbiota, and the composition of the microbiome regulates the development and function of the immune system, it is likely that an alteration of microbiota components (a dysbiosis) could influence the course of chronic spontaneous urticaria (CSU), including disease severity, patient quality of life and treatment outcome. To date, several studies have identified changes in the gut microbiota composition of patients with CSU, though only a few have exhibited metabolic abnormalities associated with gut dysbiosis. The studies on CSU patients predominantly showed that the relative abundance of beneficial bacteria was decreased (Firmicutes and Bacteroides), while that of opportunistic bacteria was increased (Enterobacteria and Proteobacteria). In addition, serum metabolome analysis revealed that gut microbiota-associated alterations in unsaturated fatty acids and the butanoate metabolism pathway may play a role in CSU. These findings are potentially associated with inflammation mediated by the imbalance of Th1/Th2/Th17 cytokines, which might contribute to CSU pathogenesis. Further research in this field could improve clinical, diagnostic, and therapeutic approaches to patients with CSU. By applying new knowledge on gut microbial communities and metabolomics, future CSU therapies could modify the microbiota composition using agents such as probiotics or other similar agents, which, in combination with current standard therapies, could hopefully lead to a reduction in symptoms and an improved quality of life for CSU patients

Diagnosis and treatment of nonmelanoma skin cancer

Bazocelularni karcinomi (BCC) i planocelularni karcinomi kože (SCC), zajedničkog naziva nemelanomski zloćudni tumori kože (NMSC), danas su najčešći zloćudni tumori u bijeloj populaciji u većine zemalja svijeta. Uzroke povećane incidencije nalazimo u djelovanju nekoliko čimbenika rizika od kojih su najvažniji povećana izloženost suncu, duže trajanje života i genetska predispozicija. Obrada bolesnika s tumorskim tvorbama suspektnim na NMSC započinje uzimanjem anamneze i fizikalnim pregledom kože. Jedna od najčešće korištenih neinvazivnih dijagnostičkih tehnika je dermatoskopija. Pregled uzorka kože dobivenog biopsijom smatra se zlatnim standardom u dijagnostici NMSC-a. Među novim dijagnostičkim tehnikama vrlo uspješnom se pokazala refleksijska konfokalna mikroskopija (RCM). Terapija NMSC-a je kirurška i nekirurška. Za veliku većinu NMSC-a, kirurške metode predstavljaju kurativni tretman jer su najbolji način odstranjenja tumora u cijelosti. Pri tom se uz standardnu eksciziju kao zlatni standard, koriste Mohsova mikrografska kirurgija (MMS) i ablativne metode. Nekirurške metode liječenja terapija su izbora za određene bolesnike te se u mnogim slučajevima stope izlječenja približavaju onima postignutima kirurgijom, a prednosti su niži troškovi liječenja te kozmetički prihvatljiviji ishod. U ove oblike liječenja ubrajamo fotodinamičku terapiju (PDT), topički 5-fluorouracil (5-FU), topičku terapiju imikvimodom, intralezijski interferon alfa-2b (IFN-α2b), radijacijsku terapiju i kemoterapiju. Nove molekularne terapije usmjerene protiv Hedgehog (Hh) signalnog puta, kao što su vismodegib i sonidegib, predstavljaju učinkovit terapijski tretman za lokalno uznapredovale/ neoperabilne BCC (laBCC) i metastaske BCC (mBCC).Basal cell carcinomas (BCC) and squamous cell carcinomas (SCC), together referred to as nonmelanoma skin cancer (NMSC), are the most commonly diagnosed malignant neoplasms in the Caucasians in most countries around the world. Causes of this condition may be found in few risk factors such as increased exposure to sunlight, longer life expectancy and genetic predisposition. Workup of patients with lesions suspicious of NMSC should begin with a history and physical examination of the skin. Dermoscopy is one of the most commonly used noninvasive diagnostic techniques. The evaluation of a sample obtained by skin biopsy is considered as the gold standard in the diagnosis of NMSC. Among novel diagnostic techniques, reflectance confocal microscopy (RCM) showed great success. Therapy of NMSCs includes surgical and nonsurgical techniques. For the vast majority of NMSCs, surgery is the curative treatment of choice as it provides the best means of controlling that the entire tumor is removed. Besides excisional surgery as gold standard, Mohs' micrographic surgery (MMS) and ablative methods can also be used. Nonsurgical methods represent a therapy option for certain patients as in many cases cure rates approach those provided by surgery, and other advantages are lower overall costs and more cosmetically acceptable outcomes. These methods include photodynamic therapy (PDT), topical 5-fluorouracil (5-FU), imiquimod therapy, intralesional interferon alfa-2b (IFN-α2b), radiotherapy and chemotherapy. Novel molecular therapies targeted against Hedgehog (Hh) signaling pathway, such as vismodegib and sonidegib, represent powerful treatment options for locally advanced/ inoperable BCCs (laBCCs) and metastatic BCCs (mBCCs)