Treatment of locally advanced and metastatic basosquamous carcinoma, navigating among sonic hedgehog pathway inhibitors, immune checkpoint inhibitors, chemotherapy, and radiotherapy: A case series and literature review.

Locally advanced (laBSCs) and metastatic basosquamous carcinomas (mBSCs) represent a therapeutic challenge. By definition, these forms are not amenable to surgery or radiotherapy, but according to literature reports, sonic hedgehog pathway inhibitors (HHIs), anti-programmed death 1 receptor antibodies (anti-PD-1), and other treatment approaches involving chemotherapy, surgery, and radiotherapy have been used. This work features 5 real-life cases of advanced BSCs, treated at the Dermato-Oncology Unit of Trieste (Maggiore Hospital, University of Trieste). In addition, a review of the current treatment options reported in the literature for laBSC and mBSC is provided, collecting a total of 17 patients. According to these preliminary data, HHIs such as sonidegib and vismodegib could represent a safe and effective first line of treatment, while the anti-PD-1 cemiplimab may be useful as a second-line option. Chemotherapy and combined approaches involving surgery and radiotherapy have been also reported to be suitable in some patients.

Emerging Hallmarks of Metabolic Reprogramming in Prostate Cancer.

Prostate cancer (PCa) is the most common male malignancy and the fifth leading cause of cancer death in men worldwide. Prostate cancer cells are characterized by a hybrid glycolytic/oxidative phosphorylation phenotype determined by androgen receptor signaling. An increased lipogenesis and cholesterogenesis have been described in PCa cells. Many studies have shown that enzymes involved in these pathways are overexpressed in PCa. Glutamine becomes an essential amino acid for PCa cells, and its metabolism is thought to become an attractive therapeutic target. A crosstalk between cancer and stromal cells occurs in the tumor microenvironment because of the release of different cytokines and growth factors and due to changes in the extracellular matrix. A deeper insight into the metabolic changes may be obtained by a multi-omic approach integrating genomics, transcriptomics, metabolomics, lipidomics, and radiomics data.

Locally advanced basal cell carcinoma: Real-life data with sonidegib.

In recent years, the category of hedgehog pathway inhibitor (HHI) has shown great results in patients with advanced basal cell carcinoma (aBCC), but few real-life data on efficacy and safety profile of sonidegib are available. We report our management of locally advanced BCCs (laBCCs) with sonidegib, also describing the favorable response of locally advanced basosquamous carcinomas (laBSCs) treated with this hedgehog signaling inhibitor. Sonidegib was generally well tolerated and it achieved high response rates, improving quality of life. Our single-center experience could be useful to better delineate long-term efficacy and tolerability profile demonstrated in the trials described in literature. Moreover, our cases provide preliminary evidence that sonidegib might be effective for laBSC.

MUC1 Tissue Expression and Its Soluble Form CA15-3 Identify a Clear Cell Renal Cell Carcinoma with Distinct Metabolic Profile and Poor Clinical Outcome.

An altered metabolism is involved in the development of clear cell renal carcinoma (ccRCC). MUC1 overexpression has been found to be associated with advanced disease and poor prognosis. In this study, we evaluated the metabolomic profile of human ccRCC, according to MUC1 expression, and integrated it with transcriptomic data. Moreover, we analyzed the role of MUC1 in sustaining ccRCC aggressiveness and the prognostic value of its soluble form CA15-3. Integrated metabolomic and transcriptomic analysis showed that MUC1-expressing ccRCC was characterized by metabolic reprogramming involving the glucose and lipid metabolism pathway. In addition, primary renal cancer cells treated with a small interfering RNA targeting MUC1 (siMUC1) migrated and proliferated at a slower rate than untreated cancer cells. After cisplatin treatment, the death rate of cancer cells treated with siMUC1 was significantly greater than that of untreated cells. Kaplan-Meier curves showed significant differences in CSS and PFS among groups of patients with high versus low levels of CA15-3. In a multivariate analysis, CA15-3 was an independent adverse prognostic factor for cancer-specific and progression-free survival. In conclusion, MUC1 expressing ccRCC is characterized by a particular metabolic reprogramming. The inhibition of MUC1 expression decreases cell motility and viability and improves cisplatin susceptibility, suggesting that this pathway can regulate de novo chemotherapy resistance in ccRCC.

Metabolomic Approaches for Detection and Identification of Biomarkers and Altered Pathways in Bladder Cancer.

Metabolomic analysis has proven to be a useful tool in biomarker discovery and the molecular classification of cancers. In order to find new biomarkers, and to better understand its pathological behavior, bladder cancer also has been studied using a metabolomics approach. In this article, we review the literature on metabolomic studies of bladder cancer, focusing on the different available samples (urine, blood, tissue samples) used to perform the studies and their relative findings. Moreover, the multi-omic approach in bladder cancer research has found novel insights into its metabolic behavior, providing excellent start-points for new diagnostic and therapeutic strategies. Metabolomics data analysis can lead to the discovery of a "signature pathway" associated with the progression of bladder cancer; this aspect could be potentially valuable in predictions of clinical outcomes and the introduction of new treatments. However, further studies are needed to give stronger evidence and to make these tools feasible for use in clinical practice.

Novel Insights into Autophagy and Prostate Cancer: A Comprehensive Review.

Autophagy is a complex process involved in several cell activities, including tissue growth, differentiation, metabolic modulation, and cancer development. In prostate cancer, autophagy has a pivotal role in the regulation of apoptosis and disease progression. Several molecular pathways are involved, including PI3K/AKT/mTOR. However, depending on the cellular context, autophagy may play either a detrimental or a protective role in prostate cancer. For this purpose, current evidence has investigated how autophagy interacts within these complex interactions. In this article, we discuss novel findings about autophagic machinery in order to better understand the therapeutic response and the chemotherapy resistance of prostate cancer. Autophagic-modulation drugs have been employed in clinical trials to regulate autophagy, aiming to improve the response to chemotherapy or to anti-cancer treatments. Furthermore, the genetic signature of autophagy has been found to have a potential means to stratify prostate cancer aggressiveness. Unfortunately, stronger evidence is needed to better understand this field, and the application of these findings in clinical practice still remains poorly feasible.

Renal Cell Carcinoma as a Metabolic Disease: An Update on Main Pathways, Potential Biomarkers, and Therapeutic Targets.

Clear cell renal cell carcinoma (ccRCC) is the most frequent histological kidney cancer subtype. Over the last decade, significant progress has been made in identifying the genetic and metabolic alterations driving ccRCC development. In particular, an integrated approach using transcriptomics, metabolomics, and lipidomics has led to a better understanding of ccRCC as a metabolic disease. The metabolic profiling of this cancer could help define and predict its behavior in terms of aggressiveness, prognosis, and therapeutic responsiveness, and would be an innovative strategy for choosing the optimal therapy for a specific patient. This review article describes the current state-of-the-art in research on ccRCC metabolic pathways and potential therapeutic applications. In addition, the clinical implication of pharmacometabolomic intervention is analyzed, which represents a new field for novel stage-related and patient-tailored strategies according to the specific susceptibility to new classes of drugs.

Neoadjuvant Therapy for Non-melanoma Skin Cancer: Updated Therapeutic Approaches for Basal, Squamous, and Merkel Cell Carcinoma.

OPINION STATEMENT: Recently introduced systemic therapies for locally advanced and metastatic non-melanoma skin cancers (NMSCs) are paving the way for neoadjuvant approach. Although none of the therapeutic options has currently gained indication in this setting, neoadjuvant approach for NMSCs is an open field and we are likely to see huge developments in the near future. Targeted therapy with sonic hedgehog pathway inhibitors is very effective in locally advanced or multiple basal cell carcinomas while immunotherapy with immune checkpoint inhibitors appears to be promising for advanced cutaneous squamous cell carcinoma and Merkel cell carcinoma. To date, targeted therapy and immunotherapy represent the frontiers in NMSC therapeutic management and, according to recent studies, good results can be achieved.

Effectiveness and tolerability of treatment for isolated actinic keratoses: A retrospective comparison between cryotherapy, CO2 laser and 5-fluorouracil 0.5%/salicylic acid 10.

Actinic keratoses (AK) have been described as either intraepithelial keratinocytic dysplasia that can evolve into invasive squamous cell carcinoma (SCC) or as in situ SCC that can progress into an invasive form. A retrospective study was conducted to compare outcomes of three different topical therapies for patients with single AK (<4): cryotherapy, CO2 laser and 5-fluorouracil 0.5%/salicylic acid 10%. We included 72 patients who presented at the Dermatology Clinic of Maggiore Hospital of Trieste between 1 November 2019 and 31 January 2020 for the treatment of AKs. All treatments led to a significant reduction in the average diameter of AK. Pain felt by patients was significantly lower after 5-FU 0.5%/SA 10%. Side effects appeared similarly distributed among the three groups, with erythema and crusts being the most frequent. Aesthetic outcomes were highest in the 5-FU 5%/SA 10% group, as evaluated by both the patient and the operator. Cryotherapy, CO2 laser and 5-FU 5%/SA 10% were all effective, with no significant efficacy differences among them. Additionally, 5-FU 5%/SA 10% was proved to have the best aesthetic result and to cause the least pain, while necessitating long-term administration. This should be taken into account for patients with low pain tolerance and low treatment adherence. Cryotherapy and CO2 laser have the advantage of requiring a single session, which might be more suitable for uncooperative patients.

Dermoscopic Findings in the Presurgical Evaluation of Basal Cell Carcinoma. A Prospective Study.

BACKGROUND: Surgery is the best treatment for basal cell carcinoma (BCC); however, incomplete excisions are possible. OBJECTIVE: Assessment of the accurateness of dermoscopy and clinical evaluation in the detection of borders of BCC and description of dermoscopic findings in clinically healthy tissue surrounding BCC. MATERIALS AND METHODS: Eighty-eight lesions with clinical dermoscopic diagnosis of BCC were examined clinically and dermoscopically, to delineate the correct site of surgical incision, demarcating the respective margins with colred dermographic pencils. Specific dermoscopic features were searched in the skin adjacent to the demarcated clinical margin. RESULTS: In 29 of 88 lesions, clinical and dermoscopic margins of the tumor coincided. In the remaining 59 (67%), 10 (16.9%) presented, in the lesion area identified under dermoscopy, classical criteria for BCC and 57 (96.6%) nonclassical criteria. Differences between clinical and dermoscopic margins were significantly more frequent in superficial BCCs (p = .006). The frequency was not significantly different (p = .85) in relation to body sites. CONCLUSION: Dermoscopy improves the identification of margins for surgical excision in BCC. The observation of nontraditional dermoscopic criteria of BCC, mainly pink-white areas and short telangiectasias in the area between clinically and dermoscopically detected margins, helps to define the actual tumoral margins and to achieve a really radical excision.

Use of noninvasive imaging in the management of skin cancer.

PURPOSE OF REVIEW: To evaluate noninvasive imaging techniques in the management of skin cancers. RECENT FINDINGS: In the last decades, a wide range of noninvasive imaging methods has been developed in the field of dermatooncology with the aim to detect and assess the several structural and molecular changes that characterize skin cancer development and progression. SUMMARY: In this review, we discuss the current and emerging applications of noninvasive imaging approaches in skin cancer management, such as digital photography, dermoscopy, ultrasound sonography, reflectance confocal microscopy, optical coherence tomography, electrical impedance techniques, Raman spectroscopy, multispectral imaging, fluorescence imaging, and multispectral optoacustic tomography.

An overview of treatment options for mild-to-moderate acne based on American Academy of Dermatology, European Academy of Dermatology and Venereology, and Italian Society of Dermatology and Venereology guidelines.

Acne is a common inflammatory skin disorder affecting the pilosebaceous unit. Patients with mild-to-moderate acne can be treated with a combination of topical, systemic, and physical therapeutic approaches, with different results depending on patient, disease, and treatment characteristics. Herein we describe and discuss the common and alternative treatment options used for mild-to-moderate acne, by comparing three widely distributed guidelines (American Academy of Dermatology, European Academy of Dermatology and Venereology, and Italian Society of Dermatology and Venereology.

Diagnosis and treatment of melanoma bone metastasis: A multidisciplinary approach.

Bone is the fourth most common site of melanoma metastasis after lung, liver, and brain. Melanoma bone metastases typically occur in patients who already have widespread metastases in other organs. Current available approaches for bone metastases from melanoma include chemotherapy, radiotherapy, biological therapy, combination therapy, and surgery. In this narrative review, we describe the management of patients affected by melanoma bone metastases, discussing the diagnostic and treatment approaches as well as their impact on survival and quality of life. Despite the fact that clinical and surgical trials will be required to determine the most appropriate treatment, we do expect a newer and more important role of multidisciplinary approach in the management of melanoma patients with bone metastases in the next future.

Benign dermatoses of the male genital areas: A review of the literature.

The male genitalia are a common site of dermatoses. Patients with penile diseases often delay or avoid medical care due to anxiety and embarrassment. In this narrative review, we describe some of the main benign dermatoses localized to male genital, focusing on their epidemiology, clinical and dermoscopic features, as well as available therapies.

Pattern of response of unresectable and metastatic cutaneous squamous cell carcinoma to programmed death-1 inhibitors: A review of the literature.

Cutaneous squamous cell carcinoma (cSCC) is the second most frequent nonmelanoma skin cancer (NMSC). The majority of in situ cSCC [cSCC (Tis)] can be cured surgically, while local advanced and metastatic ones require other treatments, but there are no therapies approved by U.S. Food and Drug Administration (FDA). Available treatments for these stages included radiotherapy, chemotherapy as cisplatin, but responses to these treatments are usually of short duration. Programmed death-1 (PD-1) inhibitors (pembrolizumab, nivolumab, and cemiplimab) are an innovative immunologic treatment that now has been shown to be useful for the treatment of advanced cSCC. Nowadays, data about the response rate with the use of PD-1 inhibitors in cSCC are still few and, especially, the duration of the response after the start of treatment is short. Moreover, the number of cases is too small to express the beneficial effects of these treatments, although most data reported in the literature show quite good response rates. This review focused on some of the studies and associated results through an interesting research on search engines of all the cases about these systemic drugs, analyzing effects and side effects, and the research has been conducted considering published cases since March 2016 to October 2019.

Italian expert consensus paper on the management of patients with actinic keratoses.

Two round tables involving experts were organized in order to reach a consensus on the management of patients with actinic keratosis (AK). In the first, seven clinical questions were selected and analyzed by a systematic literature review, using a Population, Intervention, Control, and Outcomes framework; in the second, the experts discussed relevant evidences and a consensus statement for each question was developed. Consensus was reached among experts on how to best treat AK patients with respect to different clinical scenarios and special populations. Lesion-directed treatments are preferred in patients with few AKs. Patients with multiple AKs are challenging, with more than one treatment usually needed to achieve complete lesion clearance or a high lesion response rate, therapy should be personalized, based on previous treatments, patient, and lesion characteristics. Methyl aminolevulinate-PDT, DL (day light) PDT, and imiquimod cream were demonstrated to have the lowest percentage of new AKs after post treatment follow-up. For IMQ 5% and 3.75%, a higher intensity of skin reactions is associated with higher efficacy. Photodynamic therapy (PDT) is the most studied treatment for AKs on the arms. Regular sunscreen use helps preventing new AKs. Oral nicotinamide 500 mg twice daily, systemic retinoids and regular sunscreen use were demonstrated to reduce the number of new squamous cell carcinomas in patients with AKs. Limited evidence is available for the treatment of AKs in organ transplant recipients. There is no evidence in favor or against the use of any of the available treatments in patients suffering from hematological cancer.

Clinical usefulness of dermoscopy in the management of lentigo maligna melanoma treated with topical imiquimod: A case report.

The importance of dermoscopy for diagnosing lentigo maligna melanoma (LMM) is well known. More recently, dermoscopy has been proposed as a useful tool also for the treatment choice and monitoring. Herein, we present an 87-year-old woman, who was successfully treated with imiquimod 5% cream after surgical persistence of residual LMM and for whom dermoscopy was helpful to assist diagnosis and assess tumor persistence after surgery and its response to topical treatment with imiquimod.