Prospektive Kohortenstudie von InspECT zur Sicherheit und Wirksamkeit der Elektrochemotherapie bei Hauttumoren und Metastasen in Abhängigkeit von Ulzeration.

HINTERGRUND: Elektrochemotherapie (ECT) ist eine wirksame lokale Behandlung von Hauttumoren. Ziel dieser Studie war es, die Wirksamkeit der ECT bei ulzerierten gegenüber nichtulzerierten Tumoren zu vergleichen und den Effekt auf tumorassoziierte Symptome zu untersuchen. METHODIK: 20 Krebszentren des International Network for Sharing Practices on Electrochemotherapy (InspECT) sammelten prospektiv Daten. Die ECT wurde nach dem ESOPE-Protokoll durchgeführt. Das Therapieansprechen wurde anhand der Entwicklung der Läsionsgröße bewertet. Zusätzlich wurden Schmerzen, Symptome, Leistungsstatus (ECOG-Index) und Gesundheitszustand (EQ-5D-Fragebogen) untersucht. ERGEBNISSE: 716 Patienten mit ulzerierten (n = 302) und nichtulzerierten (n = 414) Hauttumoren und Metastasen wurden eingeschlossen (Mindest-Nachsorge 45 Tage). Nicht-ulzerierte Läsionen sprachen besser auf die ECT an als ulzerierte Läsionen (vollständiges Ansprechen: 65 % gegenüber 51 %, p = 0,0061). Nur 38 % (115/302) der Patienten mit ulzerierten Läsionen vor der ECT wiesen bei der letzten Nachuntersuchung ulzerierte Läsionen auf. Patienten mit ulzerierten Läsionen berichteten über stärkere Schmerzen und schwerere Symptome im Vergleich zu Patienten mit nichtulzerierten Läsionen, die sich nach der ECT signifikant und kontinuierlich besserten. Bei Patienten mit nichtulzerierten Läsionen hingegen nahmen die Schmerzen während der Behandlung vorübergehend zu. Es wurden keine schwerwiegenden Nebenwirkungen beobachtet. SCHLUSSFOLGERUNGEN: Die ECT ist eine sichere und wirksame lokale Behandlung von Hauttumoren. Während die ECT die Symptome insbesondere bei Patienten mit ulzerierten Läsionen verbessert, sollte auf Basis der Daten die Implementation eines perioperativen Schmerzmanagements besonders bei nichtulzerierten Läsionen während der ECT erwogen werden.

Prospective cohort study by InspECT on safety and efficacy of electrochemotherapy for cutaneous tumors and metastases depending on ulceration.

BACKGROUND: Electrochemotherapy (ECT) is an effective local treatment for cutaneous tumors. The aim of this study was to compare the effectiveness of ECT in ulcerated vs. non-ulcerated tumors and investigate the effect on tumor-associated symptoms. METHODS: Twenty cancer centers in the International Network for Sharing Practices on Electrochemotherapy (InspECT) prospectively collected data. ECT was performed following ESOPE protocol. Response was evaluated by lesion size development. Pain, symptoms, performance status (ECOG-Index) and health status (EQ-5D questionnaire) were evaluated. RESULTS: 716 patients with ulcerated (n = 302) and non-ulcerated (n = 414) cutaneous tumors and metastases were included (minimum follow-up of 45 days). Non-ulcerated lesions responded to ECT better than ulcerated lesions (complete response 65 % vs. 51 %, p = 0.0061). Only 38 % (115/302) with ulcerated lesions before ECT presented with ulcerated lesions at final follow-up. Patients with ulcerated lesions reported higher pain and more severe symptoms compared to non-ulcerated lesions, which significantly and continuously improved following ECT. In non-ulcerated lesions however, pain spiked during the treatment. No serious adverse events were reported. CONCLUSIONS: ECT is a safe and effective local treatment for cutaneous tumors. While ECT improves symptoms especially in patients with ulcerated lesions, data suggest the implementation of a perioperative pain management in non-ulcerated lesions during ECT.

Purse-string suture versus full-thickness skin graft: An efficacy and safety comparison study.

Purse-string suture (PSS) and full-thickness skin graft (FTSG) are two different approaches to the closure of circular skin defects. In this study, we compare the feasibility and the aesthetic outcome of these two techniques in high operatory risk non-melanoma skin cancer (NMSC) patients. We performed a retrospective study on 65 patients, treated with PSS or FTSG, and evaluated after a minimum follow-up of 6 months. The post-surgery assessment was based on the Vancouver scar scale (VSS) and differences in terms of defect areas, operative and healing times were performed both with parametric and nonparametric tests. Operative times in PSS were significantly lower than those needed for FTSG, without perioperative adverse events; PSS required a waiting time before removing the suture greater than FTSG. After surgery, PSS resulted in a median defect area reduction of 73%. No significant differences were found in the median value for VSS in the two groups. Based on our clinical experience, the PSS advantages in terms of feasibility, rapidity of execution, and mean defect area reduction were confirmed. So, this technique seems to be appropriate for fragile patients affected by NMSC, that cannot hold long surgical sessions.

Minced Skin Grafting: A Minimally Invasive and Low-Cost Procedure to Treat Pyoderma Gangrenosum.

ABSTRACT: Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis that usually presents as a painful ulcer with erythematous and undermined borders and is often characterized by pathergy. Although this condition precludes a surgical approach, in cases resistant to treatment with immunosuppressive agents, skin grafts and amputation are considered last resorts. Both expose the patient to the risk of developing new lesions. A minimally invasive autologous graft, "minced micrografts," is a possible alternative to speed up the healing process, reducing the risk of pathergy.This procedure was implemented in a 28-year-old man with PG who was prescribed prednisone and dapsone and who had a large ulcer on the arm and armpit that had persisted for 4 months and was undergoing slow re-epithelialization. A sample of finely minced skin previously taken from the clavicular region suspended in a hydrogel was spread on the wound bed in a proportion of less than 1:6 with respect to the receiving site. Seven days later, initial signs of re-epithelialization appeared, and the wound healed in 3 months.In patients with PG, the minced micrograft method could facilitate ulcer healing by releasing cytokines, chemokines, and growth factors, thus promoting granulation tissue formation, neoangiogenesis. Because this method does not require special equipment or complex surgical techniques and is very low cost, it should be an integral part of the arsenal of procedures aimed at improving the quality of life of patients with PG.

Complete response to anti-PD-1 nivolumab in massive skin metastasis from melanoma: efficacy and tolerability in an elderly patient.

The advent of immune checkpoint inhibitors anti-PD-1/PD-L1 has delivered new and effective treatment options with proven clinical benefits for patients affected by metastatic melanoma. The 30-40% of treated patients experience an objective tumour regression, with a significantly prolonged survival and an improved quality of life. Here, we report a case of a 75-year-old Caucasian woman affected by a massive cutaneous metastasis from a BRAF wild-type melanoma who experienced multiple relapses after surgery and repeated electrochemotherapy treatments. A poor response was observed after systemic therapy with ipilimumab, whereas a marked reduction in the lesion size was obtained during the treatment with nivolumab, with an objectively complete response after 6 months. Therapy was well tolerated, without immune-related side effects. During treatment, LDH levels decreased up to the standard values. Our experience confirms the good efficacy and the safety of anti-PD-1 nivolumab for the treatment of relapsed or refractory massive skin lesions, also in elderly patients.

Temporal correlation between the first melanoma and the first noncutaneous tumor in CKDN2A genotyped patients.

CDKN2A pathogenic variants are well known to be associated with cutaneous melanoma and noncutaneous tumors (NCTs). Herein, we investigated the temporal correlation between the first cutaneous melanoma and NCT both in CDKN2A mutation carriers (MUT) and in wild-type melanoma patients, a poorly explored issue to date. Two hundred forty-five cutaneous melanoma patients were genotyped for the CDKN2A gene and divided into 51 MUT and 189 wild-type; the remaining five variant carriers were excluded from the analyses. MUT developed a significantly higher number of cutaneous melanoma than wild-type, while 13.7% in both genotyped groups received a diagnosis of at least one malignant NCT, without statistically significant differences. The onset of the first cutaneous melanoma preceded that of the first malignant or benign NCT in both MUT and wild-type patients by an average of 4.5 and 3.02 years, respectively. Considering only malignant tumors, the diagnosis of melanoma preceded that of the first NCT on an average of 8 and 4.34 years, in MUT and wild-type patients respectively. We emphasize the relevance to adopt a global vision for the primary and secondary surveillance of patients affected by cutaneous melanoma, not only limited to high-risk for multiple primary skin cancers but also to NCT that may develop several years after the diagnosis of the first cutaneous melanoma.

The impact of COVID-19 pandemics on dermatologic surgery: real-life data from the Italian Red-Zone.

BACKGROUND: The COVID-19 pandemic is challenging healthcare systems worldwide. Dermatology had to re-prioritize visits, guarantee urgent care, and ensure continuity for chronic patients. OBJECTIVES: To evaluate the COVID-19 impact on dermatologic surgery outpatient management. MATERIAL AND METHODS: In this real-life retrospective observational study, we evaluated both major and minor outpatient surgeries (MaOS and MiOS) performance in 2020, before and during the first month of lockdown declaration, in a primary referral center in Northern Italy. During the lockdown, all lifesaving and cancer surgery, (approximately 80% of our usual activities), were continued. Data from 2020 were compared with the 2019 corresponding periods to assess the real-life impact of COVID-19 in dermatologic surgical activities. RESULTS: From January 1st to April 3rd, 2020 we performed 769 interventions, compared to 908 over the corresponding 2019 period. After the lockdown, scheduled surgeries were reduced by 14.8%; overall performed ones displayed a reduction of 46.5% (51.6% MaOS, 44.2% MiOS). 52.9% and 12.5% procedures were canceled due to patients' renunciation and due to confirmed/suspected COVID-19, respectively. CONCLUSIONS: While reduced in number, dermatologic surgeries, similarly to other surgical specialties, remained operative to provide oncological and/or life-saving procedures.

COVID-19 first lockdown and outpatient hospital setting: a single center, real life study focusing on pattern changes in patients' ethnicities and treated dermatoses.

BACKGROUND: During the first Italian lockdown period, the imponent amount of hospital COVID-19 patients forced the healthcare system to re-organize visits but no information are available on outpatient ethnical patterns. Here we evaluated healthcare management changes on dermatological outpatient non-surgical settings visits during the SARS-CoV-2 pandemic. METHODS: In this retrospective study we collected data of scheduled, performed and not-performed visits, together with patients' characteristics (i.e., age, gender) with a particular attention for ethnicities among the outpatients accessing during the first Italian lockdown (March 5-April 30, 2020). Then, we compared these data with the corresponding ones in 2019 (before COVID-19 pandemic). RESULTS: During the Italian lockdown the dermatological department registered a great decrement (-83.5%, P<0.001) in visits compared to the corresponding time period in 2019. Performed and scheduled visits to non-oncological stable patients together with emergency accesses to dermatology decreased. Non-Italian patients decreased accesses, especially the South East Asians (-70.4%) and North Africans (-90.0%). CONCLUSIONS: Hospitals policy and mass media deeply condition the public opinion, and this aspect may explain a different access to the hospital among non-Italian patients. Telemedicine should be promoted especially among non-Italian communities in Italy to overgo patients' skepticism and incentivize prevention and early treatment in dermatological conditions.

Combination of Pembrolizumab with Electrochemotherapy in Cutaneous Metastases from Melanoma: A Comparative Retrospective Study from the InspECT and Slovenian Cancer Registry.

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.

Local recurrence of a primary carcinoid of the skin: a first case report.

Primary carcinoid tumors of the skin are exceptional, with only ten cases reported from 1975 to date. We describe a case of a 66-year-old woman with a primary cutaneous carcinoid developed on the scalp. The tumor was completely excised and clinical investigations as well as diagnostic studies failed to reveal internal primary site, neither at the time of the excision, neither during follow-up. Nevertheless, 7 years after the surgical excision, she developed a recurrence of the lesion on the same site. To the best of our knowledge, this is the first report of a primary relapsing carcinoid of the skin described up to now. Interestingly, the tumour expresses estroprogestinic receptors.

Melanoma-prone families: new evidence of distinctive clinical and histological features of melanomas in CDKN2A mutation carriers.

Germline mutations on the CDKN2A gene, the most important known genetic factors associated with cutaneous melanomas (CMs), predispose carriers to multiple primary CMs (MPMs) with higher frequency and younger onset compared to non-carriers. Most of the largest published studies concerning clinical and histological characteristics of CMs with CDKN2A mutation carriers did not specify if the described CMs are first or subsequent to the first, and they used sporadic CMs from non-genotyped patients as controls. We conducted a single-centre observational study to compare clinical and histological CM features of 32 unrelated carriers (MUT) of 5 germline CDKN2A mutations (one of which was never previously described) compared to 100 genotyped wild-type (WT) patients. We stratified the data based on time of diagnosis, anatomical site and histological subtype of CMs, demonstrating several significant unreported differences between the two groups. MUT developed a higher number of dysplastic nevi and MPMs. We proved for the first time that anatomical distribution of CMs in MUT was independent of gender, unlike WTs. MUTs developed in situ and superficial spreading melanomas (SSMs) more frequently, with significantly higher number of SSMs on the head/neck. In MUTs, Breslow thickness was significantly lower for all invasive CMs. When CMs were stratified on the basis of the time of occurrence, statistical significance was maintained only for SSMs subsequent to the first. In WTs, Clark level was significantly higher, and ulceration was more prevalent than in MUTs. Significant differences in ulceration were observed only in SSMs. In nodular CMs, we did not find differences in terms of Breslow thickness or ulceration between WTs and MUTs. In situ CMs developed 10 years earlier in MUTs with respect to WTs, whereas no significant differences were observed in invasive CMs. In contrast to those reported previously by other authors, we did not find a difference in skin phototype.