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Venous malformation (VM) is the most common type among vascular malformations classified by the International Society for the Study of Vascular Anomalies. Most VMs are sporadic (94%), caused in 40% of cases by somatic mutation of TEK gene. VMs can be cutaneous, visceral, or combined. Visceral involvement is rare, and gastrointestinal (GI) tract is the most common localization. Visceral VMs, usually asymptomatic, may manifest with bleeding, anemia, and consumptive coagulopathy, which sometimes require an emergency treatment. Our aim is to study the possible GI involvement in patients with only one cutaneous VM. We analyzed a series of six patients who presented with a single cutaneous VM and have subsequently manifested intestinal involvement at our reference center for vascular anomalies since 2010. In our patients, cutaneous VMs were located on lower or upper limbs, and GI involvement manifested from 3 to 10 years after skin diagnosis. Our experience urges to early diagnose a GI involvement also in patients with only one skin VM and to prevent severe complications. A multidisciplinary approach is mandatory for the diagnosis and treatment of these patients., (© 2021 Wiley Periodicals LLC.)

Infantile haemangiomas are very common benign tumours in the first months of life. They are mostly cutaneous; however, extracutaneous lesions are possible, and occur in very rare cases in the central nervous system. A European multicentre observational retrospective study was conducted in the last 5 years. Seven patients with intracranial or intraspinal infantile haemangiomas were selected and treated with oral propranolol. Propranolol was interrupted after complete or almost complete resolution of infantile haemangiomas. All patients tolerated the treatment well without side-effects. Central nervous system infantile haemangiomas are probably underestimated due to the frequent absence of symptoms and their spontaneous involution. However, they should be investigated in case of segmental cutaneous infantile haemangiomas, particularly on the head, neck, upper trunk, lumbar or sacral area in order to diagnosis intra-central nervous system involvement at an early stage.

Background: Cutaneous recurrence from breast cancer can pose a clinical challenge. It might be the only disease site, or could be part of disseminated disease, and often profoundly affects quality of life. Electrochemotherapy is a palliative treatment using electric pulses to locally permeabilize tumor cells and thereby significantly increase bleomycin cytotoxicity. Collaborating with the International Network for Sharing Practice on ElectroChemoTherapy (INSPECT), we consecutively and prospectively accrued data on patients treated with electrochemotherapy for cutaneous metastases from breast cancer., Patients and Methods: Patients were treated with electrochemotherapy at 10 European centers. Under either local or general anaesthesia patients were treated with either local injection (1000 IU/mL intratumoral) or systemic infusion (15,000 IU/m 2 ) of bleomycin., Results: One hundred nineteen patients were included at 10 institutions in the INSPECT network. The primary location was the chest (89%), the median diameter of the cutaneous metastases was 25 mm. Ninety patients were available for response evaluation after 2 months. Complete response was observed in 45 patients (50%), partial response in 19 (21%), stable disease in 16 (18%), and progressive disease in 7 (8%). Three patients were not evaluable. Common side effects were ulceration, long-lasting hyperpigmentation, and low-grade pain. No serious adverse events were observed., Conclusion: Electrochemotherapy showed high response rates after a single treatment. Electrochemotherapy has few side effects and can be used as an adjunct to systemic therapies or as a solo treatment. We therefore recommend considering electrochemotherapy for patients with cutaneous metastases., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Electrochemotherapy (ECT) is currently used to treat unresectable superficial tumours of different histotypes through the combination of cytotoxic chemotherapy and local application of electric pulses. In 2006, a collaborative project defined the ESOPE (European Standard Operating Procedures of Electrochemotherapy) guidelines to standardize the procedure. The International Network for Sharing Practices of Electrochemotherapy (InspECT) aims to refine the ESOPE and improve clinical practice. Limiting patient exposure to systemic chemotherapy would be advisable to ameliorate ECT safety profile., Objective: The aim of this study was to evaluate the efficacy and toxicity of ECT with reduced chemotherapy dosages., Methods: In a retrospective analysis of a prospectively maintained database (InspECT registry), we evaluated the outcome of patients who received ECT with reduced dosages of bleomycin (7500, 10 000 or 13 500 IU/m 2 , instead of the standard dose of 15 000 IU/m 2 ). Tumour response in melanoma patients was compared with melanoma patients of the InspECT registry who received the standard dose of bleomycin., Results: We identified 57 patients with 147 tumours (melanoma, 38.6%; squamous cell carcinoma, 22.8%; basal cell carcinoma, 17.5%; breast cancer 7%; Kaposi sarcoma 7%; other histotypes, 7.1%). Per-tumour complete response (CR) rate at 60 days was 70.1% (partial, 16.3%); per-patient CR was 57.9% (partial, 21.1%). Local pain was the most frequently reported side-effect (n = 22 patients [39%]), mostly mild; two patients experienced flu-like symptoms, one patient nausea. We observed the same CR rate (55%) in patients with melanoma treated by reduced or conventional bleomycin dosages (P = 1.00)., Conclusions: Electrochemotherapy performed with reduced bleomycin dosages could be as effective as with currently recommended dose. Patients with impaired renal function or candidate to multiple ECT cycles could benefit from a reduced dose protocol. Our findings need prospective confirmation before being adopted in clinical practice., (© 2017 European Academy of Dermatology and Venereology.)

Background: The management of non-melanoma skin cancers may benefit from alternative treatments and in this spectrum electrochemotherapy plays a pivotal role. The aim was to describe the predictive features of patients with cutaneous carcinomas treated with electrochemotherapy, with regard to clinical, pathological and instrumental predictors., Methods: We analyzed disease free survival (DFS), and overall survival (OS) for each patient. Assuming that the effects of the predictor variables are constant over time, the independent predictive factors were assessed by Cox-proportional hazards regression in both univariate and multivariate analyses., Results: We can assess that in the brief-term (DFS), the patients' age, tumor-site, tumor size, photo-type and the dose of the cytotoxic drug showed a statistical significant better behavior. However, in the multivariate, only the variables tumor's site (P=0.01) and tumor appearance (P=0.03) reached the statistical significance. In the long-term, female patients, patients with a median age ≤70 years, with III-IV photo types and patients, which received a dosage of bleomycin, ≤14 mg/m2 presented a significant better behavior. However in the multivariate analysis a significance was maintained for the variables tumor's appearance (HR: 11.6; 95% CI: 11.56 to 27.5; P=0.01), infiltration (HR:0.11; 95% CI: 0.012 to 0.9; P=0.04), electrode type (HR:0.19; 95% CI:0.04 to 0.8; P=0.03) and photo type (HR:5.7; 95% CI:1.3 to 24.3; P=0.01)., Conclusions: According to our results, in electrochemotherapy different individual variables can have an important influence, which shows how this treatment could improve. The refinement of the technique and the optimization of patients' selection has the aim to improve the therapeutic response.

Background: (ECT) is an effective local treatment for cutaneous metastasis. Treatment involves the administration of chemotherapeutic drugs followed by delivery of electrical pulses to the tumour., Objectives: To investigate the effectiveness of ECT in cutaneous metastases of melanoma and to identify factors that affect (beneficially or adversely) the outcome., Methods: Thirteen cancer centres in the International Network for Sharing Practices on Electrochemotherapy consecutively and prospectively uploaded data to a common database. ECT consisted of intratumoral or intravenous injection of bleomycin, followed by application of electric pulses under local or general anaesthesia., Results: In total, 151 patients with metastatic melanoma were identified from the database, 114 of whom had follow-up data of 60 days or more. Eighty-four of these patients (74%) experienced an overall response (OR = complete response + partial response). Overall, 394 lesions were treated, of which 306 (78%) showed OR, with 229 showing complete response (58%). In multivariate analysis, factors positively associated with overall response were coverage of deep margins, absence of visceral metastases, presence of lymphoedema and treatment of nonirradiated areas. Factors significantly associated with complete response to ECT treatment were coverage of deep margins, previous irradiation of the treated area and tumour size (< 3 cm). One-year overall survival in this cohort of patients was 67% (95% confidence interval 57-77%), while melanoma-specific survival was 74% (95% confidence interval 64-84%). No serious adverse events were reported, and the treatment was in general very well tolerated., Conclusions: ECT is a highly effective local treatment for melanoma metastases in the skin, with no severe adverse effects noted in this study. In the presence of certain clinical factors, ECT may be considered for local tumour control as an alternative to established local treatments, or as an adjunct to systemic treatments., (© 2017 British Association of Dermatologists.)

Background: The main purposes of this study were to evaluate the efficacy of electrochemotherapy in head and neck tumors, to assess local tumor control, its safety profile and its impact on the patients' quality of life., Methods: This is a multicenter prospective, non-randomized phase II trial. This trial was carried out at the Dermatology Clinic of the "Sapienza" University of Rome, at the Dermatology Clinic of the University of Chieti and at the Dermatology Clinic of the University of Turin. Fifty-five patients with head and neck cancer were recruited. Electrochemotherapy was carried out according to the ESOPE guidelines. Statistical analyses were performed using Stata/SE v.12.0 Statistical Software., Results: A significant clinical response was achieved in 50/55 patients with 91% of objective response rate (OR). Thirty-three out of 55 patients showed a complete response (CR) (60%); 17 treated patients had a partial response (PR) (31%). A significantly higher CR rate was obtained in patients not previously treated by surgery (15/19; 79%), with respect to those with a previous excision of the tumor (14/30; 47%) (P=0.025). An additional parameter influencing response is represented by anesthesia: patients treated by ECT with general anesthesia were characterized by significantly higher CR rate (68%) than those treated with local anesthesia (27%) (P=0.014)., Conclusions: Our experience confirmed high efficiency in local tumor control, excellent toxicity profile, tissue preservation with good cosmetic and functional results, even with repeated applications. ECT can represent a first-line treatment in the local management of head and neck cancers.

Background: Cutaneous metastases represent a therapeutic challenge. An increasing body of experience suggests that electrochemotherapy (ECT) provides effective tumor control, although its evidence basis should be strengthened., Methods: This prospective, multicenter, observational study enrolled patients with superficial metastases, who underwent ECT at 10 centers between 2008 and 2013. Outcomes included adherence to European Standard Operating Procedures of ECT (ESOPE), tumor response, local progression-free survival (LPFS), toxicity and patient-reported outcomes (PROs, EORTC QLQ-C30 plus an 8-item questionnaire)., Results: We enrolled 376 eligible patients. Tumor histotype distribution was as follows: melanoma, 56%; squamous cell carcinoma, 11%; Kaposi sarcoma, 11%; breast carcinoma, 8%; basal cell carcinoma, 6%; soft tissue sarcomas, 3%; others, 5%. We registered 1304 target tumors (median size 1 cm). Treatment adhered to ESOPE in 88% of patients as to the route of drug administration, and in 70% as to electrode application. The procedure was mainly performed under sedation (64.6%) and by using intravenous chemotherapy (93.4%). Tumor response rate at 60 days was 88% (complete, 50%). Small tumor size predicted complete response achievement (OR 2.24, p = 0.003), higher LPFS (HR 0.68, p = 0.004) and improved PROs (Global Health Status, p < 0.001; wound bleeding, p < 0.001; healing, p = 0.002; and aesthetics, p < 0.001). Skin toxicity (grade ≥3, 7.8%) was lower in patients with tumors <2 cm (p≤0.001). One-year LPFS was 73.7% (95%CI 68.4-78.3)., Conclusions: ECT represents a valuable skin-directed therapy across a range of malignancies. The most frequently applied treatment modality is intravenous chemotherapy under sedation. Small tumor size predicts durable tumor control, fewer side-effects and better PROs., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Angiosarcoma is an aggressive vascular neoplasm with a high propensity for local recurrence. Electrochemotherapy is an emerging skin-directed therapy, exerting prominent cytotoxic activity, and antivascular effects. Its efficacy in angiosarcoma has not been investigated., Methods: This multicenter retrospective analysis reviewed patients who underwent electrochemotherapy from 2007 to 2014 for superficial advanced angiosarcomas. Bleomycin was administered intravenously and delivered within tumors by means of percutaneously applied electric pulses, according to the European Standard Operating Procedures for Electrochemotherapy. Tumor assessment was performed using RECIST (version 1.1). Toxicity (CTCAE, v4.0) and local progression-free survival (LPFS) were also evaluated., Results: Nineteen patients (13 with locally advanced and 6 with metastatic angiosarcomas) were treated. Tumor sites were: scalp (n = 5), breast (n = 8), other skin sites (n = 3), and soft tissue (n = 3). Target lesions (n = 54) ranged in size from 1.5 to 2.5 cm (median, 2 cm). Treatment was well tolerated. After 2 months, an objective response was observed in 12/19 (63%) patients, complete in 8 (42%). One-year LPFS within treatment field was 68%. Local symptom improvement included palliation of bleeding (5/19 patients) and pain relief (6/19 patients)., Conclusions: Electrochemotherapy may represent a new locoregional treatment for selected patients with superficial angiosarcomas. J. Surg. Oncol. 2016;114:246-253. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Background: Electrochemotherapy describes the use of electric pulses to enhance chemotherapy uptake, and has proven highly efficient in treating cutaneous metastases. Patients referred for electrochemotherapy present with diverse clinical pictures, from multiple small lesions to large, ulcerated lesions. Post-electrochemotherapy pain has been observed in some patients. The objectives of this study were to evaluate pain scores before and after electrochemotherapy, and to investigate if patients at risk of post-procedure pain could be identified., Methods: Seven cancer centres in the International Network for Sharing Practices on Electrochemotherapy (INSPECT) consecutively and prospectively reported to a common database. Electrochemotherapy consisted of intratumoural or intravenous injection of bleomycin, followed by delivery of electric pulses in local or general anesthesia., Results: Of 121 patients 39% had metastatic melanoma, 18% squamous cell carcinoma, 16% breast cancer, 13% basal-cell carcinoma, and 14% other malignancies. Median size of the largest nodules was 2.3 cm (range 0.3-40 cm). A majority of patients presented with low pain scores, and this continued through follow-up (74%). A subset of patients had moderate (13%) or severe pain (13%) after treatment. Post-procedure pain was statistically significantly associated with: 1) moderate or severe pain before treatment (p<0.0001); 2) size of the largest treated lesion (p<0.01); 3) previous irradiation (p<0.02); and 4) high treatment current value (p<0.0001)., Conclusion: The majority of patients had no or mild pain after electrochemotherapy. Patients at risk for post-procedure pain could be identified at the pre-treatment visit, and/or at the time of treatment, enabling a pain management strategy for this group.

Background: Electrochemotherapy (ECT) is an emerging treatment for cutaneous lesions of different tumor types. The combination of chemotherapy and electroporation enhances drug uptake into tumoral cells. However, its role in the treatment of Kaposi sarcoma (KS) has not yet been well defined, and to date, literature reports are scarce. We prospectively evaluated clinical activity and safety of ECT in KS patients., Methods: Twenty-three patients with histologically confirmed unresectable KS, not treatable by radiotherapy or intralesional vincristine therapy, were enrolled onto the study according to the European Standard Operating Procedures of Electrochemotherapy (ESOPE) guidelines and treated with a pulse generator., Results: A response to the first ECT session was obtained in all patients, with a complete response (CR) in 14 (60.9%) of 23 patients. A second ECT was performed in 5 (21.7%) and a third in 2, with a median interval between two sessions of 5.1 (range 2.5-25.5) months. Overall, a total of 15 patients (65%) experienced a CR. After a median follow-up of 1.5 years (range 2 months to 4.2 years), 16 patients maintained the response, 4 after repeated courses. Sustained local control of treated lesions was present in 20 of 23 patients. The overall survival rate was 74.4% at 2 years., Conclusions: ECT represents an additional therapeutic tool for the management of KS cutaneous lesions, characterized by a definite clinical activity and long-lasting remissions. The absence of systemic side effects and the low impact on the immune system also make this treatment suitable for elderly people, even with repeated courses.

Basal cell carcinoma is the most common cutaneous malignant tumor, accounting for up to 80% of non melanoma skin cancers. Surgery, radiotherapy and chemotherapy have been for long time the main options for its treatment. Electrochemotherapy (ECT) is a novel local treatment successfully used in primary skin tumors. We report a case of a man affected by ulcerated basal cell carcinoma treated with ECT. In our case ECT was successful in the management of extensive basal cell carcinoma in clinical conditions whereas other approaches, would have been dangerous and inappropriate. To our knowledge, ECT must be considered as an alternative of traditional techniques when they are contraindicated in relation to the appearance of the lesions or the patient medical history.