Ingenol mebutate therapy in erythroplasia of Queyrat: a new approach.

BACKGROUND: Erythroplasia of Queyrat (EQ) is a rare squamous cell carcinoma in situ, usually occurring on the glans penis, the prepuce, or the urethral meatus. Therapy is mandatory because it can progress to invasive carcinoma in up to 30% of cases. Treatment options include 5-fluorouracil, curettage, cryotherapy, radiotherapy, laser, partial or total penectomy, and microsurgery, as also with imiquimod and photodynamic therapies. METHODS: Between 2015 to 2018 we treated five patients, with histologically confirmed EQ, with ingenol mebutate (IM) 0.015% gel applied for 3 days consecutively. RESULTS: Three patients showed complete response at one year follow up. Two patients showed partial response after two months, so they received a second course of therapy with IM. At one-year follow-up, one of them showed complete response, the other partial response. CONCLUSIONS: Our experience demonstrated that IM may be considered as an effective and safe treatment option in EQ. IM offers various advantages such as easy and fast application, rapid complete remission, better compliance, few side effects and excellent cosmetical results. The authors call for further exploitation in bigger trials.

Do Diet and Lifestyles Play a Role in the Pathogenesis of NMSCs?

BACKGROUND AND AIMS: Literature highlights the role of risk factors like age, body mass index (BMI), tobacco smoking, alcohol intake and diet in the pathogenesis of several cancer types but little is known for non-melanoma skin cancers (NMSC). The aim of this epidemiological study was to evaluate the correlation between modifiable risk factors (BMI, metabolic panel, diet, lifestyle, medical history) and not modifiable risk factors (gender, age) and NMSC development. METHODS: From February 2018 to September 2019, 162 patients affected by NMSC were compared to a group of 167 controls. A univariate and multivariate analysis was conducted to elaborate the data collected through face-to-face interviews. RESULTS: While our evidence did not always reach statistical significance, NMSC study group patients exhibited high rates of analyzed risk factors (male gender aging over 55 years, high BMI, reduced physical activity) compared to the control group. CONCLUSIONS: Our study indicates that practicing more than 30 min of physical activity daily could be a protective factor against the NMSC onset. Other risk factors were not correlated with NMSC, but more evidence is needed to establish a possible link.

Mechanisms of Acquired BRAF Inhibitor Resistance in Melanoma: A Systematic Review.

This systematic review investigated the literature on acquired v-raf murine sarcoma viral oncogene homolog B1 (BRAF) inhibitor resistance in patients with melanoma. We searched MEDLINE for articles on BRAF inhibitor resistance in patients with melanoma published since January 2010 in the following areas: (1) genetic basis of resistance; (2) epigenetic and transcriptomic mechanisms; (3) influence of the immune system on resistance development; and (4) combination therapy to overcome resistance. Common resistance mutations in melanoma are BRAF splice variants, BRAF amplification, neuroblastoma RAS viral oncogene homolog (NRAS) mutations and mitogen-activated protein kinase kinase 1/2 (MEK1/2) mutations. Genetic and epigenetic changes reactivate previously blocked mitogen-activated protein kinase (MAPK) pathways, activate alternative signaling pathways, and cause epithelial-to-mesenchymal transition. Once BRAF inhibitor resistance develops, the tumor microenvironment reverts to a low immunogenic state secondary to the induction of programmed cell death ligand-1. Combining a BRAF inhibitor with a MEK inhibitor delays resistance development and increases duration of response. Multiple other combinations based on known mechanisms of resistance are being investigated. BRAF inhibitor-resistant cells develop a range of 'escape routes', so multiple different treatment targets will probably be required to overcome resistance. In the future, it may be possible to personalize combination therapy towards the specific resistance pathway in individual patients.

Therapeutic Options for the Treatment of Actinic Keratosis with Scalp and Face Localization.

Actinic keratosis (AK) is a common skin disease related to ultraviolet chronic exposure, that is now considered a squamous cell carcinoma in situ. Primary skin cancer prevention strategies should be recommended for high risk patients. There is a wide spectrum of treatment options available for AKs, and several variables should be taken into account regarding the best therapeutic choice for each patient. The purpose of this article is to review the current treatment strategies for AKs localized on the face and scalp, with a focus on the practical point of view that could be useful for choosing the best therapeutic option. The two main therapeutic approaches will be distinguished first: lesion-directed and field-directed. Afterwards, the treatment based on clinical type and patient comorbidity will be discussed.

BRAF Inhibitors: Molecular Targeting and Immunomodulatory Actions.

The BRAF inhibitors vemurafenib, dabrafenib and encorafenib are used in the treatment of patients with BRAF-mutant melanoma. They selectively target BRAF kinase and thus interfere with the mitogen-activated protein kinase (MAPK) signalling pathway that regulates the proliferation and survival of melanoma cells. In addition to their molecularly targeted activity, BRAF inhibitors have immunomodulatory effects. The MAPK pathway is involved in T-cell receptor signalling, and interference in the pathway by BRAF inhibitors has beneficial effects on the tumour microenvironment and anti-tumour immune response in BRAF-mutant melanoma, including increased immune-stimulatory cytokine levels, decreased immunosuppressive cytokine levels, enhanced melanoma differentiation antigen expression and presentation of tumour antigens by HLA 1, and increased intra-tumoral T-cell infiltration and activity. These effects promote recognition of the tumour by the immune system and enhance anti-tumour T-cell responses. Combining BRAF inhibitors with MEK inhibitors provides more complete blockade of the MAPK pathway. The immunomodulatory effects of BRAF inhibition alone or in combination with MEK inhibition provide a rationale for combining these targeted therapies with immune checkpoint inhibitors. Available data support the synergy between these treatment approaches, indicating such combinations provide an additional beneficial effect on the tumour microenvironment and immune response in BRAF-mutant melanoma.

Erythroplasia of Queyrat treated with methyl aminolevulinate-photodynamic therapy.

Erythroplasia of Queyrat (EQ) is a rare disease involving the mucosal and transitional surfaces of the penis. Effective treatment is necessary to minimize progression to squamous cell carcinoma. The standard therapy for EQ, partial or radical penectomy, is invasive; photodynamic therapy (PDT) may be an effective, non-surgical tissue-sparing option. We report the case of a 67-year-old patient with long-standing EQ who was suc-cessfully treated with methyl aminolevulinate-PDT (MAL-PDT). A complete clinical response, confirmedby incisional biopsy, was achieved af-ter fivesessions of every-other-week treatment. The patient experienced moderate edema, erythema and pain within 5-7 days after the treatment, without urination problems. Our experience and a review of the published literature suggest that MAL-PDT may represent a valuable treatment option for selected cases of histopathologically-confirmed EQ.

IL-17 and its role in inflammatory, autoimmune, and oncological skin diseases: state of art.

Recent data support the theory of the involvement of IL-17 in the pathogenesis of several chronic inflammatory skin diseases (psoriasis, atopic dermatitis, acne, hidradenitis suppurativa) and autoimmune skin diseases (alopecia areata, vitiligo, bullous diseases). Even if the role of IL-17 in inflammatory and autoimmune diseases has been reported extensively, its role in tumor is still controversial. Some reports show that Th17 cells eradicate tumors, while others reveal that they promote the initiation and early growth of tumors. Herein, we review the role of IL-17 in the involvement of some common dermatologic diseases: psoriasis, atopic dermatitis, hidradenitis suppurativa, acne, vitiligo, melanoma, and nonmelanoma skin cancers.

Face and Scalp Basal Cell Carcinoma Treatment: A Review of the Literature.

Basal cell carcinoma (BCC) is the most frequent skin cancer and is characterized by slow growth, even if it can be locally invasive and rarely metastasizes. Many different phenotypic presentations and histopathologic subtypes have been described, and the current guidelines subdivide BCCs into low-risk (nodular and superficial) and high-risk subtypes (micronodular, infiltrating, and morphoeic BCC and those with squamous differentiation). Dermoscopy allows the identification of the features associated with these different subtypes. Compared with the low-risk forms of BCC, more aggressive ones tend to undergo more frequently incomplete surgical excision and perineural invasion, so the identification of these lesions before surgery is extremely important. The gold standard of treatment is surgery, particularly for the H region of the face and infiltrative lesions, but other options are available and selected according to many variables, including body area, age, comorbidities, and clinical, dermoscopic, and histopathological features of the lesion. Moreover, the possible complications of surgical approaches, namely healing defects, failure of skin grafts, and wound infection, should be considered. In this review we discuss the management of BCC localized on the face and scalp, according to the currently available treatment options.

A Review of the Literature of Surgical and Nonsurgical Treatments of Invasive Squamous Cells Carcinoma.

Cutaneous squamous cell carcinoma (cSCC) is an increasing public health problem. It is a primary malignant skin tumor with Malpighian differentiation and together with basal cell carcinoma is classified among nonmelanoma skin cancers (NMSCs). cSCC usually occurs on photoexposed areas, such as the head, the neck, and the extremities, and its incidence increases with age. Invasive forms of this skin tumor tend to be more aggressive showing a higher metastatic potential, usually regarding regional lymph nodes. Treatment options for invasive cSCCs include both surgical and nonsurgical options. The therapeutic choice depends on several factors, such as anatomic location, risk factors for tumor recurrence, age, and health status of the patient. This review aims to provide an overview of the current evidence on therapeutic surgical and nonsurgical management of invasive cSCC.

Adult Acne Versus Adolescent Acne: A Retrospective Study of 1,167 Patients.

Background: Acne is predominantly known as a skin disorder of the adolescent population. However, current research indicates that the prevalence of adult patients with acne, especially among women, is increasing. Objective: The objective of this study was to evaluate differences between adults and teenagers with regard to acne prevalence, patient sex, acne severity, and quality of life. In adult patients, we considered differences in family history of acne, onset, and smoking habits. Design: We performed a retrospective study of a total of 1,167 patients with acne who attended our outpatient clinic from January 2008 to March 2015. Participants: The study population was divided into two groups: adolescent acne and adult acne. Among the adult subjects, 385 were female and 69 were male; among the adolescent subjects, 378 were female and 335 were male. Measurements: The severity of acne was recorded using the Global Acne Grading System. The impact of acne on quality of life was investigated using the Assessment of Quality of Life questionnaire. Results: Study results show that acne in female patients was more prevalent than in male patients. The evaluation of acne severity showed that "mild acne" is the most frequent form. With regard to smoking habits, time of onset, and family history of acne, we did not find any statistically significant differences between the sexes. Conclusion: In both sexes, there are some differences in adult acne versus the adolescent form. Treating adult acne demands a different approach to diagnosis and a tailored management plan that considers all of the variables involved.

Factors influencing response to ingenol mebutate therapy for actinic keratosis of face and scalp.

AIM: To determine factors independently influencing response to ingenol mebutate therapy and assess efficacy on clinical setting of non-hypertrophic non-hyperkeratotic actinic keratosis (AK). METHODS: Consecutive patients affected by non-hypertrophic non-hyperkeratotic AKs of the face or scalp were enrolled to receive ingenol mebutate 0.015% gel on a selected skin area of 25 cm2 for 3 consecutive days. Local skin reactions were calculated at each follow up visit using a validated composite score. Efficacy was evaluated by the comparison of clinical and dermoscopic pictures before the treatment and at day 57, and classified as complete, partial and poor response. RESULTS: A number of 130 patients were enrolled, of which 101 (77.7%) were treated on the face, while 29 (22.3%) on the scalp. The great majority of our study population (n = 119, 91.5%) reached at least a 75% clearance of AKs and, in particular, 58 patients (44.6%) achieved a complete response while 61 (46.9%) a partial one. Logistic backward multivariate analysis showed that facial localization, level of local skin reaction (LSR) at day 2, the highest LSR values and level of crusts at day 8 were factors independently associated with the achievement of a complete response. CONCLUSION: Ingenol mebutate 0.015% gel, when properly applied, is more effective on the face than on the scalp and efficacy is directly associated to LSR score.

Cardiovascular risk evaluation through heart rate variability analysis in psoriatic patients before and after 24 weeks of etanercept therapy: Prospective study.

OBJECTIVE: To assess the influence of etanercept, an anti-tumour necrosis factor (TNF)-α agent, on autonomic cardiovascular regulation in young patients with moderate-to-severe psoriasis without cardiovascular risk factors. METHODS: Patients with psoriasis underwent 5-min electrocardiogram (ECG) recordings before and after 24 weeks of etanercept therapy. Linear heart rate variability (HRV) analysis was performed. RESULTS: The study recruited 19 patients. Frequency-domain analysis showed a significant decrease in oscillatory components attributable to sympathetic activity (LF%) and a significant decrease in low frequency/high frequency (LF/HF) ratio following etanercept therapy. CONCLUSION: Treatment with etanercept in patients with moderate-to-severe psoriasis could affect cardiovascular autonomic regulation, and subsequently reduce cardiovascular risk.

Isotretinoin for the treatment of squamous cell carcinoma arising on an epidermoid cyst.

A 63-year-old man showed multiple concentric erythemato-nodular lesions of approximately 1.5-3 cm in diameter, located in the parietal and temporal region. The skin biopsy allowed histological diagnosis of infundibular epidermal cyst associated with chronic granulomatous flogosis; in one of these, a well-differentiated squamous cell carcinoma arising from the cyst wall was found. The patient received isotretinoin at the daily dosage of 0.5 mg/kg/day for 5 months. During 1-year follow-up, laboratory tests, computed tomography scans, and control histology were all in the normal range, with a good improvement of the lesions. Epidermal cysts and squamous cell carcinoma are both commonly encountered in practice. However, the association of epidermal inclusion cysts and squamous cell carcinoma in the skin is very rare. In some cases, including the present one, more potent chemopreventive strategies, such as the use of systemic retinoids, must be considered. Systemic retinoids are the most heavily researched chemopreventive agents and have shown promise for multiple types of cancer, including bladder and head and neck carcinomas. We would like to recommend the possibility to administer retinoids in a squamous cell carcinoma, achieving very satisfactory results; in our case, a complete remission of malignant lesion and an improvement of epidermal cysts were made, without the development of side effects associated with retinoids.