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Incidence of melanoma has been increasing in both sexes in the last decades. Advanced melanoma has always been one of the deadliest cancers worldwide due to his high metastatic capacity. In the last ten years, progresses in the knowledge of the molecular mechanisms involved in the melanoma development and progression, and in immune-response against melanoma, empowered the development of two new classes of systemic therapeutic agents: target-therapies and immunotherapies. Both classes consist of monoclonal antibodies inhibiting specific molecules. Target-therapies are selectively directed against cells harboring the BRAFV600-mutation, while immunotherapies target the two molecules involved in immune-checkpoint regulation, enhancing the immune response against the tumor: cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death-1 receptor (PD-1). Target- and immunotherapy demonstrated to improve both progression-free and overall survival in melanoma patients either in metastatic or in adjuvant settings. Several drugs have been approved in recent years as monotherapy or in combination, and many other drugs are currently under investigation in clinical trials. In the current review on new systemic therapies for cutaneous melanoma, we revised the molecular basis and the mechanisms of actions of both target- and immunotherapy (why). We discussed who are the best candidate to receive such therapies in both the adjuvant and metastatic setting (who) and which were the most important efficacy and safety data on these drugs (what).

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.

In a controlled study of 100 patients, mean age 65 years old, suffering from chronic peripheral obliterative arterial disease, Leriche's stage II, were randomised in two groups treated respectively with defibrotide (400 mg bid) or heparan-sulfate (40 mg bid) by the oral route for a period of 6 months. At basal and after 30, 90 and 180 treatment days, patients were assessed for pain, paresthesias, rigidity and or tiredness in the leg, Winsor index (WI) relative and absolute walking distance (RWD, AWD), and time of recovery from pain. In order to evaluate microcirculation the following parameters were tested: resting flow (RF), standing flow (SF), veno-arteriolar reflex (VAR) and a capillaroscopy study was conducted. All patients showed an improvement in the clinical and instrumental parameters but more pronounced in the defibrotide group; the difference between the beginning and the end of the therapy was significantly better for defibrotide (p < 0.01). The tolerability observed was good, no side-effects were reported during the study.