Cutaneous Melanoma and Sentinel Lymph Node Biopsy; An Epidemiology Study of Population Level Data.

Aims Cutaneous melanoma accounts for 90% of all melanoma cases diagnosed. In addition, the incidence of cutaneous melanoma is increasing by approximately 3-7% yearly, and it is the most rapidly increasing cancer diagnosed in white populations worldwide. The aim of this study is to assess the survival benefit of Sentinel Lymph Node Biopsy (SLNB) in cutaneous melanoma in an Irish population. Methods Population based data was obtained from the National Cancer Registry of Ireland (NCRI) on all patients with a cutaneous melanoma diagnosed over a 20-year period 1994-2014 and predictors of Overall Survival (OS) were assessed. Results 13302 patients were identified with a melanoma diagnosis between 1994-2014. OS varied with gender, age, smoking and marital status, anatomical location and TMN stage. 2196 (17%) patients underwent SLNB, which included 710 patients in the stage 1 melanoma category (<11% of this group). Undergoing a SLNB was not an independent predictor of improved OS (p=0.440). However, a positive SLNB result was an independent predictor of OS (0.001). Conclusion This Irish population-based data re-affirms demographic indicators of poorer survival. A positive SLNB result indicates poorer survival; however, the precedent itself is not a predictor of OS.

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 for the treatment of primary basal cell carcinoma; A randomised control trial comparing electrochemotherapy and surgery with five year follow up.

Basal cell carcinoma (BCC) are the commonest cutaneous malignancy and incidence continues to increase. There is a need to expand the therapeutic toolbox to increase options for patients that are unsuitable for or unwilling to undergo the current therapies. Electrochemotherapy (ECT) is a technique where cells are temporarily permeabilized after exposure to a brief pulsed electrical field and combined with low dose chemotherapeutics to ablate malignancies. It is a simple technique causing minimal damage to the surrounding healthy tissue and has the potential to avoid the need for complex reconstruction. ECT is an established treatment for skin metastases but its role as a primary treatment modality is not demonstrated. A prospective randomised control trial evaluating ECT against the gold standard of treatment, Surgery, was performed for patients with primary BCC and patients followed for 5 years. All lesions treated with ECT (n = 69) responded although 8/69 (12%) needed a second treatment to ensure a complete response. All surgical lesions (n = 48) showed histological evidence of complete excision with 2/48 (4%) undergoing a second excision. At 5 years, in the surgical arm there was no evidence of recurrence in 39/40 (97.5%) lesions with 1/40 (2.5%) confirmed recurrence. In the ECT arm there was no evidence of recurrence in 42/48 lesions (87.5%). There was 5 confirmed recurrences. These groups show statistical equivalence in this non inferiority study design (p = 0.33). ECT is an effective and durable treatment option for primary BCC and should be considered as part of the armamentarium of options available.

When do we think it is Safe to Drive after Hand Surgery? - Current Practice and Legal Perspective.

Patients recovering from hand surgery frequently ask when it is safe to drive and it is unclear where the responsibility lies; the surgeon, the patient or the insurance company. An eight-question survey looking at various aspects of clinical practice was circulated to consultant and trainee plastic and orthopaedic surgeons in Ireland and the UK. Of the 89 surgeons who replied, (53%) felt the decision when to drive was the patient's compared with the insurance company (40%) and the surgeon (7%). 80% advised patients to contact their insurance company. 87% were unaware of current regulations or guidelines. National guidelines were vague and left the decision with the treating doctor. Similarly, major insurers advise patients to contact their doctor for advice. From a legal standpoint, the patient has a duty of care to other road users to be in full control of his vehicle prior to driving, regardless of any advice received.

Mesenchymal Stem Cells and Cutaneous Wound Healing: Current Evidence and Future Potential.

Human skin is a remarkable organ that sustains insult and injury throughout life. The ability of skin to expeditiously repair wounds is paramount to survival. With an aging global population, coupled with a rise in the prevalence of conditions such as diabetes, chronic wounds represent a significant biomedical burden. Mesenchymal stem cells (MSC), a progenitor cell population of the mesoderm lineage, have been shown to be significant mediators in inflammatory environments. Preclinical studies of MSC in various animal wound healing models point towards a putative therapy. This review examines the body of evidence suggesting that MSC accelerate wound healing in both clinical and preclinical studies and also the possible mechanisms controlling its efficacy. The delivery of a cellular therapy to the masses presents many challenges from a safety, ethical, and regulatory point of view. Some of the issues surrounding the introduction of MSC as a medicinal product are also delineated in this review.

Fibrin as a delivery system in wound healing tissue engineering applications.

Fibrin is formed in the body upon initiation of the clotting cascade and is produced commercially for use as a tissue sealant and hemostasis device during surgical procedures. Experimentally fibrin is being increasingly used as a vector to deliver growth factors, cells, drugs and genes in tissue engineering applications mimicking aspects of the extra cellular matrix. Growth factors (GFs) are central to wound healing, inducing cell proliferation, migration and differentiation. Attempts have been made to augment wound healing with GFs, however widespread clinical use has been hindered in vivo due to their rapid metabolism within the body. Fibrin hydrogels protect GFs from rapid degradation and the composition of which can be altered to achieve their optimal release. This article reviews the use of fibrin for the delivery of GFs and details the various strategies that have evolved to alter the release rate so as to enhance the regenerative process, including bi-domain peptides, plasmin degradation sequences and heparin incorporation. This paper also reviews other recent advances in this field, such as dual delivery of cells and GF or sequential release of multiple GF.

The extent of soft tissue and musculoskeletal injuries after earthquakes; describing a role for reconstructive surgeons in an emergency response.

BACKGROUND: Earthquakes are the leading cause of natural disaster-related mortality and morbidity. Soft tissue and musculoskeletal injuries are the predominant type of injury seen after these events and a major reason for admission to hospital. Open fractures are relatively common; however, they are resource-intense to manage. Appropriate management is important in minimising amputation rates and preserving function. This review describes the pattern of musculoskeletal and soft-tissue injuries seen after earthquakes and explores the manpower and resource implications involved in their management. METHODS: A Medline search was performed, including terms "injury pattern" and "earthquake," "epidemiology injuries" and "earthquakes," "plastic surgery," "reconstructive surgery," "limb salvage" and "earthquake." Papers published between December 1992 and December 2012 were included, with no initial language restriction. RESULTS: Limb injuries are the commonest injuries seen accounting for 60 % of all injuries, with fractures in more than 50 % of those admitted to hospital, with between 8 and 13 % of these fractures open. After the first few days and once the immediate lifesaving phase is over, the management of these musculoskeletal and soft-tissue injuries are the commonest procedures required. CONCLUSIONS: Due to the predominance of soft-tissue and musculoskeletal injuries, plastic surgeons as specialists in soft-tissue reconstruction should be mobilised in the early stages of a disaster response as part of a multidisciplinary team with a focus on limb salvage.

Electrochemotherapy for the treatment of ocular basal cell carcinoma; a novel adjunct in the disease management.

Basal Cell Carcinoma (BCC) affecting the ocular region is potentially problematic due to its ability to infiltrate aesthetic and functional structures. Due to the paucity of local tissue, resection frequently requires reconstruction with skin grafts or local flaps. Surgical treatment may not be suitable for patients with multiple co-morbidities. Electrochemotherapy (ECT) is a technique where cells are temporarily permeabilized after exposure to a brief electrical field and when combined with normally impermeant chemotherapy drugs can resolve cutaneous cancers - even those previously recalcitrant to chemotherapy or radiotherapy. Its particular advantage is its speed of application and the minimal damage to the surrounding healthy tissue structures. We present a series of 3 patients with BCCs in the peri-ocular region and significant co-morbidities deemed unsuitable for surgical resection, who underwent ECT. The lesions were all primary BCC ranging in size from 0.5 cm(2) to 1 cm(2). Two lesions were on the upper eyelid and one on the lower eyelid. ECT was performed using an 8-needle electrode and a CE approved electroporation generator with intra-lesional Bleomycin. All lesions responded to treatment. All BCC's completely resolved, with acceptable scarring. No side effects were reported from the Bleomycin or the electric pulses. ECT for peri-ocular BCC is an adjunct to surgical excision in the management of surgically problematic lesions. This technique could provide a useful initial treatment option for patients who are medically unfit or where resection and would be associated with significant morbidity.

Reversal of hand peripheral ischaemia due to extravasation of adrenaline during cardiopulmonary resuscitation.

A 63 year old woman sustained an extravasation of vasopressor during a successful in hospital cardiopulmonary resuscitation resulting in an acutely ischaemic hand. This was treated with multiple washouts of the hand due to incipient recurrence of the ischaemia. Extravasation of vasopressor is exceedingly rare and potentially devastating. This case highlights the specific problems associated with extravasation of vasopressor. We present an algorithm for treatment of these and identify the potential need to use specific antidotes for the vasoconstriction caused by adrenaline extravasation.

Improved angiogenic cell penetration in vitro and in vivo in collagen scaffolds with internal channels.

Porous scaffolds are limited in volume due to diffusion constraint and delay of vascular network formation. Channels have the potential to speed up cellular penetration. Their effectiveness in improving angiogenic cell penetration was assessed in vitro and in vivo in 3-D collagen scaffolds. In vitro, channelled and non-channelled scaffolds were seeded with vascular smooth muscle cells. Results demonstrated that the scaffolds supported angiogenic cell ingrowth in culture and the channels improved the depth of cell penetration into the scaffold (P < 0.05). The cells reside mainly around and migrate along the channels. In vivo, channels increased cell migration into the scaffolds (P < 0.05) particularly angiogenic cells (P < 0.05) resulting in a clear branched vascular network of microvessels after 2 weeks in the channelled samples which was not apparent in the non-channelled samples. Channels could aid production of tissue engineered constructs by offering the possibility of rapid blood vessel infiltration into collagen scaffolds.

Comfort care in burns: the Burn Modified Liverpool Care Pathway (BM-LCP).

INTRODUCTION: Despite advances in burn care some injuries remain non survivable. Good end of life care for these patients is arguably as important as life prolonging care. The Liverpool Care Pathway is a useful tool for providing good quality end of life care. It has previously been modified for the acute setting. We modified it further specifically for use in burn care in 2007 and would like to share our experience of using it. METHODS: A retrospective case series of deaths occurring between 01/01/08 and 31/12/09 is presented and adherence to the Burn Modified Liverpool Care Pathway (BM-LCP) is assessed. RESULTS: There were 22 deaths over the study period with a mean TBSA of 55%. Mean Acute Burn Severity Index score (ABSI) 12.5. A decision of futility was made in 14 cases, 11 of these were started on the BM-LCP. 7 were started on the pathway at the time of admission. Mean time from decision to start the pathway to death 11 h (range 3-48). There were no variances from the pathway. CONCLUSION: The BM-LCP appears to be an appropriate tool for assisting in end of life care in burns and when used appears to improve end of life care. We recommend its use and would encourage others to implement its use.

Prospective analysis of waiting times for emergency plastic surgery in four units.

INTRODUCTION: Trauma is a significant part of the workload in plastic surgery. There are currently wide variations in the available resource for dealing with these patients. Delays to treatment currently exist and may result in poorer clinical outcomes. METHOD: Data was collected prospectively in 4 centres (Cork University Hospital, John Radcliffe Hospital, Stoke Mandeville Hospital and Salisbury District Hospital) assessing delays to theatre. We assessed time to theatre, both from injury and from review, cancellation rate, starvation time and patient satisfaction. RESULTS: 424 patients were audited over an 8-week period. The average time from review to theatre was 15.7 h and the average injury-to-theatre time was 58.6 h. The average starvation time was 10 h; the mean cancellation rate was 25%. Patients are satisfied overall with the service provided with 83% rating the service as excellent or good, and 63% feeling that there wait was not too long. CONCLUSIONS: Despite an increase in provision of emergency plastic surgery trauma lists, the average wait for emergency plastic surgery is increasing. Despite this patients remain, on the whole, satisfied with the service that they are receiving.

Macrophage-mediated degradation of crosslinked collagen scaffolds.

Biological scaffolds used in tissue engineering are incorporated in vivo by a process of cellular in-growth, followed by host-mediated degradation and replacement of these scaffolds, in which phagocytic cells from the monocyte/macrophage cell lineage play a key role. The chemical degradation of scaffolds with collagenases is well established, but to date this has not been correlated with an in vitro model of cell mediated scaffold degradation. RAW264.7, a murine monocyte/macrophage cell line, was cultured on collagen scaffolds crosslinked either by dehydrothermal treatment (DHT) or by carbodiimide (EDC). These cells attached to collagen scaffolds, proliferated and exhibited macrophage aggregation to form giant cells. Crosslinking the scaffolds by either DHT or EDC increased the resistance of the scaffold to degradation by macrophages. Increasing the amount of crosslinking in the scaffold made them more resistant to degradation by collagenase. However, while EDC increased the scaffolds' thermal and mechanical properties and decreased the swelling ratio, DHT increased the mechanical properties, but decreased the denaturation temperature and swelling ratio. Altering the scaffold properties by crosslinking affects the rate of degradation by macrophages, and this is correlated with chemical degradation (r=0.658, p<0.01). This will help in the design of scaffolds with task-specific profiles for use in tissue engineering.