This study aimed to evaluate the effects of comorbidities, neoadjuvant chemotherapy, haemoglobin levels, and nutritional status on a novel model of ex-vivo wound healing. Human skin samples were obtained from surgical waste of patients undergoing plastic and reconstructive procedures. Ex vivo wounds were created using punch biopsies, cultured over a 48-hour healing time course, and analysed for mean healed area (%). Patient records were reviewed for comorbidities, smoking status, preoperative chemoradiotherapy, and haemoglobin and albumin levels. Data analysis was conducted using univariate and multivariate regression analyses to identify predictors of wound healing outcomes. A total of 64 ex vivo donor skin samples were analysed, with a mean area healed at 48 hours of 69.3% ± 20.3% and a median of 71.7%. Smoking, obesity, nutrition, haemoglobin, neoadjuvant chemotherapy, diabetes, autoimmune disease, or preoperative immunosuppressant use were not significant predictors of mean area healed at 48 hours (all p values > 0.05). However, concurrent autoimmune disease and immunosuppressant use significantly reduced the mean area healed (p = 0.048; 95% CI: [-1.86, -0.01]). The ex vivo model examined real patient samples, offering insights into wound healing variability. No significant effects of smoking, obesity, nutrition, haemoglobin, or neoadjuvant chemotherapy were observed on healing outcomes. However, autoimmune disease and immunosuppressant use significantly reduced healing. Larger, diverse cohorts with extended follow-up are needed to address subgroup limitations. This model highlights the complexity of wound healing and its potential to bridge laboratory findings with clinical practice, enabling personalised medicine.

This study aimed to assess the association between clinical risk factors, treatment-related variables, and postoperative wound complications in breast reconstructive surgery. This retrospective cohort study included patients undergoing reconstructive breast surgery at a single centre between August 2017 and January 2024. Data on risk factors, including obesity, smoking status, age, diabetes mellitus, hypertension, preoperative haemoglobin levels, nutritional status, and preoperative use of immunosuppressants, chemotherapy, and targeted anticancer therapy eg: Herceptin were collected. Wound healing outcomes were classified using the breast reconstruction specific Clavien-Dindo classification. Relationships were evaluated using an ordered multivariate logistic regression. A total of 215 patients were included (mean age 51.4 ± 10.1 years). Preoperative therapies included chemotherapy (48.6%), radiotherapy (37.7%), oestrogen receptor blockers (15.5%), aromatase inhibitors (18.8%), and targeted anticancer drugs (15.6%). Obesity was identified as a strong predictor of higher-grade complications according to the Clavien-Dindo classification (OR = 3.17 [95% CI: 1.77–5.67], p < 0.001). Preoperative targeted anticancer drugs (OR = 0.36 [95% CI: 0.15–0.84], p = 0.018), nutrition scores (OR = 1.16 [95% CI: 1.04–1.30], p = 0.007), and immunosuppressant use (OR = 3.43 [95% CI: 1.01–10.90], p = 0.036) were also significant predictors of higher-grade complications (p<0.05) . The model was statistically significant (p = 0.0013). Targeted anticancer therapies, obesity, nutrition, and immunosuppressant use significantly influence wound complication severity. Preoperative optimisation and individualised risk stratification are crucial to reducing surgical wound complications. Future research should explore underlying mechanisms using ex vivo models and develop standardised wound reporting criteria for breast reconstruction.

Published data on the combination of immunotherapy and electrochemotherapy (ECT) consistently indicate a benefit in tumor response, but an important question, the optimal timing for combination, remains unclear. We investigated the impact of the timing of the ECT/immunotherapy combination. A cohort of 170 stage IIIC–IV melanoma patients from the Insp-ECT registry were evaluated for toxicity and local, systemic and long-term responses after combined ECT/immunotherapy treatment. Three groups were compared: patients who received immunotherapy before, during and after ECT. Combined treatment with ECT did not increase the toxicity profile of ECT. The best response was achieved with concomitant treatment with ECT. After 2 months, the local response was 61

The aim of this multicenter study was to evaluate the effectiveness and safety of electrochemotherapy (ECT) for the treatment of mucosal tumors in the head and neck.A total of 71 patients with 84 nodules of different histologies in the oral cavity, pharynx and larynx treated by ECT were evaluated. The data were collected from the InspECT database from 10 participating centers throughout Europe.Primary and recurrent/secondary tumors of different histologies were treated. The overall response rate was 65%, with a 33% complete response rate with limited side effects. The response rates of the primary and secondary tumors were not different. However, smaller tumors responded better than tumors larger than 3 cm in diameter. Furthermore, the tumors that were treated with curative intent responded significantly better than those treated with palliative intent.This study demonstrated the feasibility, safety and effectiveness of ECT in a larger cohort of patients with mucosal lesions in the head and neck region. Based on the available data, ECT can be used for the treatment of recurrent and, in some cases, primary mucosal tumors located in the oral cavity, larynx, and pharynx. A better response was obtained in patients with smaller primary tumors treated with curative intent.

Background: Lymph node surgery is commonly performed in the staging and treatment of metastatic skin cancer. Previous studies have demonstrated sentinel lymph node biopsy (SLNB) and, particularly, lymph node dissection (LND) to be plagued by high rates of wound complications, including surgical site infection (SSI) and seroma formation. This study evaluated the incidence of wound complications following lymph node surgery and provided the first published cost estimate of SSI associated with lymph node surgery in the UK.Patients and methods: A retrospective cohort study of 169 patients with a histological diagnosis of primary skin malignancy who underwent SLNB or LND of the axilla and/or inguinal region at a single tertiary centre over a 2 year period was conducted. Demographic, patient risk factor, and operation characteristics data were collected and effect on SSI and seroma formation was analysed. Cost-per-infection was estimated using National Health Service (NHS) reference and antibiotic costs.Results: A total of 146 patients underwent SLNB with a SSI rate of 4.1% and a seroma incidence of 12.3%. Twenty-three patients underwent LND with a SSI rate of 39.1% and a seroma incidence of 39.1%. Seroma formation was strongly associated with the development of SSI in both the SLNB (odds ratio (OR) = 18.0, p < 0.001) and LND (OR = 21.0, p = 0.007) group. The median additional cost of care events and treatment of SSI in the SLNB and LND groups was 199.46 pound and 5187.04 pound, respectively.Conclusion: SSI remains a troublesome and costly event following SLNB and LND. Further research into perioperative care protocols and methods of reducing lymph node surgery morbidity is required and could result in significant cost savings to the NHS.(c) 2023 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

BackgroundElectrochemotherapy has gained international traction and commendation in national guidelines as an effective tool in the management of cutaneous malignancies not amenable to surgical resection. Despite this, no level 5 evidence exists comparing it to radiotherapy in the treatment of cutaneous malignancies. This systematic review aimed to examine the literature directly and indirectly comparing electrochemotherapy and radiotherapy in the treatment of primary cutaneous malignancies or cutaneous metastases from primary solid organ malignancies. Materials & methodsThe protocol for this review was registered on the PROSPERO International Prospective Register of Systematic Reviews with the protocol ID CRD42021285415. Searches of MEDLINE, Embase, CINAHL, CENTRAL and ClinicalTrials.gov databases were undertaken from database inception to 28 December 2021. Studies in humans comparing treatment with electrochemotherapy to radiotherapy and reporting tumour response with a minimum four week follow-up were eligible. Risk of bias was assessed using the ROBINS-I tool. Results are provided as a narrative synthesis. ResultsTwo case series with a total of 92 patients were identified as relevant to this study. Both case series examined patients with cutaneous squamous cell carcinoma. One case series examined elderly patients with predominantly head/neck lesions. The other examined younger patients with predominantly limb lesions who had cutaneous squamous cell carcinoma directly attributable to a rare skin condition. ConclusionThere is little literature presenting comparative data for electrochemotherapy and radiotherapy in the treatment of primary cutaneous malignancies or cutaneous metastases. Included studies were marred by serious risk of bias particularly due to confounding. The inherent bias and heterogeneity of the included studies precluded synthesis of a consolidated comparison of clinical outcomes between the two therapies. Further research is required in this domain in the form of clinical trials and observational studies to inform guidelines for electrochemotherapy treatment.

BACKGROUND:Skin metastases are an important co-morbidity in melanoma. Despite broad adoption, electrochemotherapy implementation is hindered by a lack of treatment indications, uncertainty regarding procedural aspects, and the absence of quality indicators. An expert consensus may harmonize the approach among centres and facilitate comparison with other therapies. METHODS:An interdisciplinary panel was recruited for a three-round e-Delphi survey. A literature-based 113-item questionnaire was proposed to 160 professionals from 53 European centres. Participants rated each item for relevance and degree of agreement on a five-point Likert scale, and received anonymous controlled feedback to allow revision. The items that reached concordant agreement in two successive iterations were included in the final consensus list. In the third round, quality indicator benchmarks were defined using a real-time Delphi method. RESULTS:The initial working group included 122 respondents, of whom 100 (82 per cent) completed the first round, thus qualifying for inclusion in the expert panel (49 surgeons, 29 dermatologists, 15 medical oncologists, three radiotherapists, two nurse specialists, two clinician scientists). The completion rate was 97 per cent (97 of 100) and 93 per cent (90 of 97) in the second and third rounds respectively. The final consensus list included 54 statements with benchmarks (treatment indications, (37); procedural aspects, (1); quality indicators, (16)). CONCLUSION:An expert panel achieved consensus on the use of electrochemotherapy in melanoma, with a core set of statements providing general direction to electrochemotherapy users to refine indications, align clinical practices, and promote quality assurance programmes and local audits. The residual controversial topics set future research priorities to improve patient care.

Electrochemotherapy has been proven to be an efficient treatment for cutaneous metastases of various cancers. Data on breast cancer (BC) patients with cutaneous metastases were retrieved from the INSPECT database. Patients were divided by their receptor status: HER2+, HR+ (ER/PgR+), and TN (triple negative). Groups were similar for histological subtype and location of the nodules. Most patients were previously treated with surgery/systemic therapy/radiotherapy. We found no differences in the three groups in terms of response ratio (OR per patient 86% HER2+, 80% HR+, 76% TN, p = 0.8664). The only factor positively affecting the complete response rate in all groups was small tumor size (<3 cm, p = 0.0105, p = 0.0001, p = 0.0266, respectively). Local progression-free survival was positively impacted by the achievement of complete response in HER2+ (p = 0.0297) and HR+ (p = 0.0094), while overall survival was affected by time to local progression in all groups (p = 0.0065 in HER2+, p < 0.0001 in HR+, p = 0.0363 in TN). ECT treatment is equally effective among groups, despite different receptor status. Response and local tumor control seem to be better in multiple small lesions than in big armor-like lesions, suggesting that treating smaller, even multiple, lesions at the time of occurrence is more effective than treating bigger long-lasting armor-like cutaneous lesions.

Abstract Introduction For completion of staging of malignant melanoma, sentinel lymph node biopsy (SLNB) may be offered to patients with stage 1B disease or greater, and in some positive cases, completion lymphadenectomy is offered. However, there is little evidence that either procedure are beneficial to patients, and both procedures carry a risk of wound complications. The aim of this study was to assess the current prevalence of wound complications in these procedures and quantify the change over time of this risk. Methods This was a subgroup analysis of a larger systematic review (Prospero CRD42021239530). A systematic search was undertaken to identify all published material relating to surgery on the lymph nodes. The primary outcome was the proportion of surgical site infection and/or seroma. Studies relating to malignant melanoma were selected from the overall results, and random effects meta-analysis of proportions and meta-regression were undertaken. Results Seventy studies were suitable for inclusion in meta-analysis, constituting 7,585 patients. The proportion of patients developing infection following SLNB was 3.5% (95% CI 2.0–6.0%) and seroma 7.8% (4.0–14.3%). For completion lymphadenectomy, the risk of SSI was 17.4% (13.4– 22.2%) and seroma 24.7% (23.4–26.0%). Neither SSI nor seroma incidence have changed significantly in 30 years. Conclusion The risk of complications in these procedures remains high and has not changed in 30 years. Given a potential lack of benefit of these procedures, this data should be used as part of the decision-making process when counselling patients, and to guide future research into prevention of wound complications. Take-home message The risk of SSI following block dissection for melanoma is almost 20%, and the risk of seroma almost 25%. This unacceptably high risk has not improved in the last 30 years.

IntroductionCutaneous squamous cell carcinoma (cSCC) is a frequent skin cancer with a high risk of recurrence characterized by tumor infiltration and, in advanced cases, a poor prognosis. ECT (electrochemotherapy) is an alternative treatment option for locally advanced or recurrent cSCC that is unsuitable for surgical resection. In this study, we aimed to evaluate the data in the InspECT (International Network for Sharing Practice on ECT) registry of the referral centers and to clarify the indications for the use of ECT as a treatment modality for cSCC.Materials and methodsPatients with primary, recurrent or locally advanced cSCC from 18 European centers were included. They underwent at least one ECT session with bleomycin between February 2008 and November 2020, which was performed following the European Standard Operating Procedures.ResultsThe analysis included 162 patients (mean age of 80 years; median, 1 lesion/patient). Side effects were mainly local and mild (hyperpigmentation, 11%; ulceration, 11%; suppuration, 4%). The response to treatment per patient was 62% complete and 21% partial. In the multivariate model, intravenous drug administration and small tumor size showed a significant association with a positive outcome (objective response). One-year local progression-free survival was significantly better (p<0.001) in patients with primary tumors (80% (95% C.I. 70%-90%) than in patients with locally advanced disease (49% (95% C.I. 30%-68%).ConclusionIn the present study, ECT showed antitumor activity and a favorable safety profile in patients with complex cSCC for whom there was no widely accepted standard of care. Better results were obtained in primary and small tumors (<3 cm) using intravenous bleomycin administration.

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.

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.

BackgroundMalignancies that spread to the lymph nodes may be identified through surgical biopsy, and treatment of metastatic disease may be through lymph node dissection. These surgeries, however, may be associated with significant adverse outcomes, particularly wound complications, the true incidence of which remains unknown. Multiple studies have reported their individual rates of complications in isolation. The aim of this study will be to systematically evaluate data that presents the incidence of wound complications in patients undergoing these surgeries.MethodsWe have designed and registered a protocol for a systematic review and meta-analysis of studies presenting incidence data. We will search MEDLINE, EMBASE and CENTRAL for relevant articles. Meta-analysis will be undertaken to synthesise an overall incidence of surgical site infection, wound dehiscence, haematoma and seroma. Subgroup analyses will investigate the effects of anatomical location, primary malignancy and study design on pooled incidence. Risk of bias will be evaluated for each included study using bespoke tools matched to the study design.DiscussionThe results of this study will provide the incidence of wound complications and secondary complications following lymph node surgery. This will directly impact upon the consent process, and may influence the nature of future research studies aimed at reducing post-operative complications.

Dear Editor, The latest British Association of Dermatologists guidelines1 for the management of basal cell carcinoma (BCC) have once again established a robust framework, highlighting advances in the management of the most common skin cancer in the UK. Inclusion of the novel biologic drug vismodegib offers a unique opportunity for a subgroup of the population who have developed ‘advanced BCC’ and for patients with the genodermatosis Gorlin syndrome.1 Treatment options for locally advanced BCC (laBCC) and metastatic BCC (mBCC) include surgery, radiotherapy and, in rare selected cases, cytotoxic chemotherapy. When these options are not appropriate, best supportive care is advised. Up until its withdrawal from the Cancer Drugs Fund (CDF) in 2017,2 vismodegib offered a hopeful therapeutic option for these patients. Recommendation 14 of the new guidelines offers vismodegib ‘as a treatment option to adults with advanced BCC who are unsuitable for Mohs micrographic surgery, standard surgical excision or radiotherapy, including patients with Gorlin syndrome, following discussion at an MDT (multidisciplinary team).’1 Unfortunately, vismodegib does not have National Institute for Health and Care Excellence (NICE) or CDF approval for these indications. In view of this, we feel the guidelines should provide further clarification on the use of this novel drug.

We read with interest the article by Dale et al. and it provides a valuable addition to the literature. [1] Dale J. Rayatt S. White N. Evriviades D. Baden J Anatomical location of the primary tumour and its relationship to regional lymph node metastasis in cutaneous head and neck melanoma: is selective neck dissection appropriate?. J Plast Reconstruct Aesthet Surg. 2019; 20: 46 Google Scholar The evidence regarding optimal neck dissection for regional control of head and neck cutaneous malignant melanoma is limited, and precise management of the neck has frequently been omitted from the major sentinel lymph node biopsy (SLNB) trials, even when queried for subsequent study design by us. Anatomical location of the primary tumour and its relationship to regional lymph node metastasis in cutaneous head and neck melanoma: Is selective neck dissection appropriate?Journal of Plastic, Reconstructive & Aesthetic SurgeryVol. 73Issue 4PreviewCurrent practice in managing regional disease in head and neck melanoma is with a comprehensive neck dissection. The knowledge that this does not afford a survival benefit combined with recent encouraging advances in immunotherapy do raise the question if a lesser procedure such as a selective neck dissection (SND) would be more appropriate. We would like to invite discussion into the prospect of using this treatment in malignant cutaneous melanoma of the head and neck. Full-Text PDF

In this centre, patients with pT4b cutaneous melanoma are staged using 18F-FDG PET-computed tomography (PET-CT) prior to considering sentinel lymph node biopsy (SLNB). The objective was to assess the utility of PET-CT in terms of rates of detection of metastases leading to changes in planned treatment and if performing PET-CT was associated with a delay in surgical management. In this single-centre retrospective cohort study, 88 consecutive patients with pT4b melanoma were identified from February 2014 to May 2019. Data were collected from clinical records. Of the 88 patients, 76 patients underwent PET-CT and 16/76 (21%) of these demonstrated metastatic/potentially metastatic disease. In total 16/76 (21%) patients had positive findings on PET-CT, and of these 14 (18%) had alterations to their clinical care. Performing PET-CT did not significantly delay time to wide local excision (PET-CT median 74 days (range 16-220) vs. no PET-CT median 55 days (range 36-143) P = 0.56) or SLNB (PET-CT median 67 days (range 16-206) vs. no PET-CT median 124 days (range 45-203) P = 0.66). Of the 29 patients undergoing SLNB who had negative PET-CT findings, 12/29 (41%) demonstrated microscopic metastatic disease. At the median follow-up of 1.75 years, 28 patients (34%) had died. Median survival was not reached. Performing staging PET-CT prior to SLNB in patients with pT4b melanoma can reveal metastases in over a fifth of patients, leading to alteration in management without treatment delay. Due to the low sensitivity of PET-CT for small metastases, SLNB remains important for definitive staging.

The objective of this study was to quantitatively compare outcomes between standard excision (SE) and Mohs micrographic surgery (MMS) for basal cell carcinoma (BCC). A systematic review and meta-analysis were performed as per the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) Guidelines and a search of electronic databases was conducted to identify all randomised controlled trials (RCTs) and observational studies comparing the outcomes of SE versus MMS for BCC. The primary outcome was the recurrence rate for primary and recurrent BCC. The secondary outcomes included the cost of treatment, aesthetic results, the rate of incomplete excision, and the surgical defect size post excision. Five studies enrolling 2060 lesions were identified. There was a statistically significant difference between MMS and SE groups in terms of recurrence rate for primary BCCs (odds ratio (OR) = 0.44, confidence interval (CI) = 0.16 to 0.97, P = 0.04) and recurrent BCCs (OR = 0.33, CI = 0.12 to 0.97, P = 0.04). For secondary outcomes, MMS had improved results compared with SE, except for mean cost. In conclusion, both primary and secondary BCCs treated with MMS have a reduced recurrence rate and defect size thus simplifying reconstruction. However, due to higher costs and operative time attributed to MMS, it should be reserved for high-risk BCCs.