Electrochemotherapy in the treatment of cutaneous malignancy: Outcomes and subgroup analysis from the cumulative results from the pan-European International Network for Sharing Practice in Electrochemotherapy database for 2482 lesions in 987 patients (2008-2019).

BACKGROUND: Electrochemotherapy (ECT) is a treatment for both primary and secondary cutaneous tumours. The international Network for sharing practices on ECT group investigates treatment outcomes after ECT using a common database with defined parameters. METHODS: Twenty-eight centres across Europe prospectively uploaded data over an 11-year period. Response rates were investigated in relation to primary diagnosis, tumour size, choice of electrode type, route of bleomycin administration, electrical parameters recorded and previous irradiation in the treated field. RESULTS: Nine hundred eighty-seven patients, with 2482 tumour lesions were included in analysis. The overall response (OR) rate was 85% (complete response [CR]: 70%, partial response rate: 15%, stable disease: 11%, and progressive disease: 2%). For different histologies, OR and CR rates for metastases of malignant melanoma were 82% and 64%, basal cell carcinoma were 96% and 85%, breast cancer metastases were 77% and 62%, squamous cell carcinoma were 80% and 63% as well as Kaposi's sarcoma were 98% and 91%, respectively. Variance was demonstrated across histotypes (p < 0.0001) and in accordance with size of lesion treated (dichotomised at diameter of 3 cm (p < 0.0001). Hexagonal electrodes were generally used for larger tumours, but for tumours up to 3 cm, linear array electrodes provided better tumour control than hexagonal electrodes (80%:74%, p < 0.003). For tumours more than 2 cm, intravenous administration was superior to intratumoural (IT) administration (p < 0.05). Current recorded varied across tumour histologies and size but did not influence response rate. In previously irradiated areas, responses were selectively lower for IT administration. CONCLUSIONS: These cumulative data endorse efficiency of ECT across a broad range of histotypes. Analysis of 2482 lesions details subgroup analysis on treatment response informing future treatment choices.

Electrochemotherapy and Ablative Therapies in Non-melanoma Skin Cancer.

Although surgery and radiotherapy remain the most commonly used treatments for non-melanoma skin cancer, there are a variety of alternatives. Here we discuss the use of electrochemotherapy and ablative treatments and examine the evidence for their effectiveness against a number of non-melanoma skin cancers.

Electrochemotherapy in the treatment of metastatic malignant melanoma: a prospective cohort study by InspECT.

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.

Giant condylomata acuminata of Buschke and Lowenstein: A peristomal variant.

INTRODUCTION: Giant condylomata acuminata (GCA) is a rare, locally invasive tumour that may undergo malignant transformation. It was first described a HPV-induced penile tumour which clinically resembled both a squamous cell carcinoma and condyloma acuminatum, often arising from a pre-existing warty lesion. We describe a case of peri-stomal GCA transformation into invasive squamous cell carcinoma (SCC), which is, to our knowledge, the first report of this in the literature. PRESENTATION OF CASE: A 74 year old gentleman developed an acuminate, papillomatous peristomal eruption around a fifty year old ileostomy, with biopsies of the eruption showing reactive changes. Two years later, he developed ulcerating plaques affecting the previously papillomatous areas and an erythematous nodular lesion involving the superior part of the ileostomy and adjacent skin. Histological examination of the ileostomy lesion showed focal small islands of atypical squamous epithelium, and moderately differentiated invasive squamous cell carcinoma was shown in the excised tissue subsequently. Human papillomavirus (HPV type 16), p16 and p53 tumour suppressors were positive in the peri-stomal skin sample. DISCUSSION AND CONCLUSIONS: Recurring, changing papillomatous lesions in the peristomal area should be reviewed with a high index of suspicion in relation to GCA tumours as they can progress to invasive squamous cell carcinomas.

Gluteal fold flaps for perineal reconstruction.

Defects of the perineum are created during ablative procedures for gynaecological, urological and colorectal malignancies. The gluteal fold flap is a reliable means of reconstructing these defects. We retrospectively reviewed case notes of gluteal fold flaps performed for perineal reconstruction over four years (2007-2010) in our institution. 77 perineal defects were reconstructed using unilateral or bilateral gluteal fold flaps (127 flaps in total). 50% of all patients are discharged before 11 days, and 90% were discharged within one month. Mean time to discharge was 13.2 days. 70% of all patients were completely healed at 2 months, and 85% completely healed at three months. Pre-operative radiotherapy was found to have a prolonging effect on the time to discharge (P<0.05) but did not reach statistical significance when considering the eventual time to healing. The number of co-morbidities that each patient had at the time of surgery had a prolonging effect on both time to discharge and time to healing (P<0.03). The type of resected areas that required reconstruction did not have a statistically significant effect on the time to discharge, but defects where the anus had been resected did eventually take longer to heal than those were the anus was not resected (P<0.01). 124 flaps were successful (97.6%) with total or partial flap loss occurring in three. Complications were seen in 34 of the 77 patients (44%), with simple wound breakdown resulting in delayed healing seen most frequently (30%). The gluteal fold fasciocutaneous flap is a versatile option for reconstructing a wide range of pelvic and perineal defects. Patients with multiple co-morbidities, cases with radiotherapy and instances where the anus has been resected are more likely to experience longer healing times. We present our algorithm for management for perineal defects after tumour resection.

Potential use of craniosynostotic osteoprogenitors and bioactive scaffolds for bone engineering.

The cranial bone has a very limited regenerative capability. Patients with craniosynostosis (the premature fusion of cranial sutures, leading to skull abnormalities) often require extensive craniofacial reconstruction and repeated surgery. The possibility of grafting autologous osteoprogenitor cells seeded on bioabsorbable matrices is of great potential for inducing regeneration of craniofacial structure and protecting the brain from external insult. To this purpose we have studied the behaviour of normal and craniosynostotic mouse osteoblast cell lines, and of human primary osteoprogenitors from craniosynostotic patients. We have monitored their ability to grow and differentiate on plastic and on a scaffold composed of bioactive glass and bioabsorbable polymer by live fluorescent labelling and expression of bone differentiation markers. Cells from syndromic patients display a behaviour very similar to that observed in the stable mouse cell line we generated by introducing the human FGFR2-C278F, a mutation found in certain craniosynostosis, into MC3T3 osteblastic cells, indicating that the mutated cell line is a valuable model for studying the cellular response of human craniosynostotic osteoblasts. Both normal and mutated calvarial osteoprogenitors can attach to the bioactive scaffold, although mutated cells display adhesion defects when cultured on plastic. Furthermore, analysis of bone differentiation markers in human osteoblasts shows that the composite mesh, unlike PLGA(80) plates, supports bone differentiation. The ability of the mesh to support homing and differentiation in both normal and mutant osteoprogenitors is important, in view of further developing autologous biohybrids to repair cranial bone deficits also in craniosynostotic patients undergoing extensive reconstructive surgery.

Trans-nasal endo-assisted pharyngoplasty: a cadaver study.

A possible new technique of endoscopic pharyngoplasty is described and has been developed in cadavers. The trans-nasal route is used for endoscopic visualisation of the velopharyngeal sphincter. Hynes pharyngoplasty is performed using both trans-oral and trans-nasal routes. This approach allows better visualisation and performance of the Hynes pharyngoplasty at the desired level, "high" in the nasopharynx, without splitting the soft palate.

Palmar resurfacing techniques: an "ideal" opportunity and the importance of long-term follow-up.

A case involving the accidental loss of all the skin of the palm and the palmar surfaces of all four fingers, and its replacement as a full-thickness graft, is presented. The importance of long-term follow-up to detect and correct palmar skin contractures is emphasized. The literature which relates to this difficult area of loss is reviewed.

Heroin addiction as a family phenomenon: a new conceptual model.

The chronic relapsing nature of heroin addiction can be explained from a family systems viewpoint. The addiction cycle is part of a family pattern involving a complex homeostatic system of interlocking feedback mechanisms. These serve to maintain the addiction and consequently the overall family stability. Drug-taking usually starts at adolescence. It is related to an intense fear of separation experienced by the family in response to the addict's attempts at individuation. The family becomes stuck at a particular developmental stage. Heroin provides a solution at several levels to the dilemma of whether or not to allow him independence. Paradoxically, it permits him to simultaneously be both close and distant, "in" and "out", competent and incompetent, relative to his family of origin. This is pseudoindividuation. An understanding of these concepts, and their integration into a homeostatic model, can provide the basis for effective treatment.