Effectiveness of nail bed repair in children with or without replacing the fingernail: NINJA multicentre randomized clinical trial.

BACKGROUND: Surgery for nail bed injuries in children is common. One of the key surgical decisions is whether to replace the nail plate following nail bed repair. The aim of this RCT was to assess the clinical effectiveness and cost-effectiveness of nail bed repair with fingernail replacement/substitution compared with repair without fingernail replacement. METHODS: A two-arm 1 : 1 parallel-group open multicentre superiority RCT was performed across 20 secondary-care hospitals in the UK. The co-primary outcomes were surgical-site infection at around 7 days after surgery and cosmetic appearance summary score at a minimum of 4 months. RESULTS: Some 451 children presenting with a suspected nail bed injury were recruited between July 2018 and July 2019; 224 were allocated to the nail-discarded arm, and 227 to the nail-replaced arm. There was no difference in the number of surgical-site infections at around 7 days between the two interventions or in cosmetic appearance. The mean total healthcare cost over the 4 months after surgery was €84 (95 per cent c.i. 34 to 140) lower for the nail-discarded arm than the nail-replaced arm (P < 0.001). CONCLUSION: After nail bed repair, discarding the fingernail was associated with similar rates of infection and cosmesis ratings as replacement of the finger nail, but was cost saving. Registration number: ISRCTN44551796 (http://www.controlled-trials.com).

Dermatofibrosarcoma protuberans (DFSP) in children: A combined multidisciplinary approach.

Dermatofibrosarcoma protuberans (DFSP) is rare, comprising (1%-6%) of all sarcomas. The incidence is less than one per million before the age of 20. It is a locally aggressive tumor with a low risk of metastasis. We share our experience in the management of three pediatric patients with complex cases of DFSP in a combined surgical approach involving plastic and dermatologic surgery, using the slow Mohs micrographic surgery technique.

Cost-effectiveness of replacing versus discarding the nail in children with nail bed injury.

Every year in the UK, around 10 000 children need to have operations to mend injuries to the bed of their fingernails. Currently, most children have their fingernail placed back on the injured nail bed after the operation. The NINJA trial found that children were slightly less likely to have an infection if the nail was thrown away rather than being put back, but the difference between groups was small and could have be due to chance. This study looked at whether replacing the nail is cost-effective compared with throwing it away. Using data from the NINJA trial, we compared costs, healthcare use, and quality of life and assessed the cost-effectiveness of replacing the nail. It was found that throwing the nail away after surgery would save the National Health Service (NHS) £75 (€85) per operation compared with placing the nail back on the nail bed. Changing clinical practice could save the NHS in England £720 000 (€819 000) per year.

Unusual Craniofacial Distraction.

A retrospective Institutional Review Board-approved review was performed at the Institute of Reconstructive Plastic Surgery, NYU Langone Medical Center, of patients undergoing craniofacial distraction osteogenesis procedures using the rigid external distractor device between 2000 and 2010. Three particularly challenging cases were identified and are presented here.

Heinrich von Pfalzpaint, Pioneer of Arm Flap Nasal Reconstruction in 1460, More Than a Century Before Tagliacozzi.

Heinrich von Pfalzpaint (circa 1415-1465) was a Bavarian military surgeon of the Teutonic Order who treated more than 4000 casualties during the siege of Marienberg Fortress (1454-1457). In 1460, he reported "How to create a new nose if it has been chopped off and the dogs have eaten it" in his treatise on wound care Bündt-Ertznei. He used opium-soaked sponges for anesthesia, described the surgical extraction of bullets and cleft lip repair. Pfalzpaint would have been the first author to describe nasal reconstruction in Europe if his treatise had not been lost. Only 5 copies of his manuscript existed. One was rediscovered and printed in 1868. Pfalzpaint's technique for nasal reconstruction was performed in 2 stages using an undelayed skin flap from the upper arm, which was sutured to the nasal defect and the arm was bandaged to the head. After 8 to 10 days, he divided the pedicle; inset the flap; and fashioned the nasal dorsum, alae, and columella. Tagliacozzi described arm flap nasal reconstruction more than a century later in 1597. He used delayed skin flaps, with at least 6 operative stages over 4 months. Pfalzpaint was ahead of his time regarding his knowledge of wounds, insistence on surgical cleanliness, and his technically easier arm flap rhinoplasty, compared with Tagliacozzi. Pfalzpaint, who is rarely referenced in the literature, should be remembered as a great pioneer of reconstructive surgery in Europe.

Pfeiffer syndrome: analysis of a clinical series and development of a classification system.

Among the craniosynostosis syndromes, Pfeiffer syndrome is notable because of high mortality and the need for multiple surgical interventions. However, it is variable in severity. We propose a new classification of Pfeiffer Syndrome to define pathology and function. A retrospective review was conducted of 42 patients with Pfeiffer syndrome treated from 1975 to 2010, the largest series reported to date. The classification was based on a functional assessment of patients in terms of respiratory, ocular, otological, and neurological status. This classification was tested by scoring and stratifying patients as follows: type A (mild problems), B (moderate problems), or C (severe problems). Patients were scored both at the time of presentation and after all surgical interventions to assess change in functional outcome. The functional classification system was compared to another previously reported. Type A patients did not have any change in postoperative functional outcomes (mean preoperative score 1.6, mean postoperative score 1.6); type B patients showed functional improvement (mean preoperative score 4.1, mean postoperative score 3.4) but type C patients (mean preoperative score 7.7, mean postoperative score 4.8) demonstrated the greatest improvement in functional scores after surgical intervention. Suture pathology did not indicate the clinical severity of phenotype, a variance from a previously published classification. The proposed classification is useful to assess severity of phenotype: respiratory, ocular, otologic, and neurologic problems are key indicators of the need for treatment. The classification can provide a helpful guide in multidisciplinary treatment planning, in reporting outcomes, and in the sharing of data among craniofacial anomalies centers.

The Oxford Finger Nail Appearance Score - a new scoring system for fingernail deformity following paediatric finger tip trauma.

Fingernail deformity is common, yet current methods used to define cosmetic appearance following trauma are mainly descriptive. In order to quantify the cosmetic appearance of the fingernail, we developed the Oxford Fingernail Appearance Score using a three stage iterative process. The score has five cosmetic components marked as binary outcomes composed of nail shape, nail adherence, eponychial appearance, nail surface appearance and presence of a split. In the first stage, two assessors independently assessed 25 photographs of fingernails taken at a minimum of four months following paediatric nail bed repair and compared them to the corresponding contralateral uninjured finger. Following refinement in the score, ten different assessors scored a further 62 photographs of fingernails taken after paediatric nail bed repair. Assessors completed each of the five components, and the overall component score was calculated by statisticians post-hoc, taking the ideal appearance of each component as 1 ("identical to opposite" for nail shape, eponychium and surface, "complete" for adherence, "absent" for split) and all the non-ideal appearances as 0. Assessors effectively scored the photographs' integer values between 0 (least optimal appearance) and 5 (most optimal appearance). Refinements in the scoring system resulted in an improvement in a weighted kappa statistic of 0.36 (95% CI:0.09,0.68) in the initial score to 0.52 (95% CI: 0.42, 0.61). The Oxford Fingernail Appearance Score is a user-friendly and reliable scoring system which has application in a clinical trial setting.

Acellular dermal matrix reconstruction of a nail bed avulsion in a 13-year-old child.

Nail bed avulsion injuries often require reconstruction, particularly in cases where the avulsed fragment is lost. We describe a simple way to reconstruct a large nail bed defect, with no donor site. A 13-year-old boy with a hypoplastic left heart and autism accidentally sustained a left little distal phalanx injury with an avulsion of 60% of the nail bed, exposing the distal phalanx. This boy had a history of poor compliance, qualifying the need to find a technique that would minimise operative time and dressing changes. As such, it was elected to use an acellular dermal matrix (ADM) (Matriderm) as a one-step reconstruction. Signs of vascularisation of the ADM were noted at 2 weeks, and 3-month follow-up demonstrated integration, with normal nail growth. We found that Matriderm was able to support the regeneration of a full thickness wound in a simple one-step procedure.

Management of Pediatric Distal Fingertip Injuries: A Systematic Literature Review.

Nail bed and fingertip injuries are the commonest hand injuries in children and can lead to profound functional and cosmetic impairments if not appropriately managed. Fingertip injuries can present with subungual hematomas, simple or stellate lacerations, crush, or avulsion injuries, often with associated fractures or tip amputations. The fundamentals of managing nail bed injuries concern restoring the form and function of a painless fingertip. However, there are controversies surrounding the optimal management of each of these injuries, which has led to nonuniformity of clinical practice. METHODS: The PubMed database was searched from March 2001 to March 2019, using a combination of MeSH terms and keywords. Studies evaluating children (<18 years of age) and the fingertip (defined as distal to the distal interphalangeal joint) were included following screening by the authors. RESULTS AND CONCLUSION: The evidence base for the diverse clinical management strategies currently employed for fingertip injuries in the pediatric population is limited. Further studies yielding level I data in this field are warranted.

Should the nail plate be replaced or discarded after nail bed repair in children? Nail bed INJury Analysis (NINJA) randomised controlled trial: a health economic and statistical analysis plan.

BACKGROUND: Nail bed trauma is one of the most common surgically treated paediatric hand injuries in the UK. Despite surgeons generally expressing a preference to replace the nail plate after repairing the nail bed, there is limited evidence to support this practice. We describe a statistical and health economic analysis plan (SHEAP) for the Nail bed INJury Analysis (NINJA) randomised controlled trial. METHODS/DESIGN: NINJA is a multicentre, pragmatic, superiority, parallel group randomised controlled trial of the treatment of nail bed injury in participants 16 years old or younger. The study aims to evaluate the efficacy and cost-effectiveness of replacing the nail plate compared to discarding it following the repair of a nail bed injury. Surgical site infection at 7-10 days post-randomisation and cosmetic appearance of the nail are the co-primary outcomes for NINJA. Surgical site infection at 7-10 days post-randomisation will be evaluated using a logistic regression model adjusting for site as the sole stratification factor and allowing for intra-site correlation. Cosmetic appearance will be assessed via the newly developed Oxford Finger Nail Appearance Score and will be evaluated by use of a Mann-Whitney U test. An ordinal logistic regression model will also be used to assess the Oxford Finger Nail Appearance Score, adjusting for site and allowing for intra-site correlation. Secondary outcomes are measured at 7-10 days and 4 months and include the EQ-5D-Y questionnaire, pain at first dressing change, cost-effectiveness, late surgical site infection, and participant/parent satisfaction with nail healing. Missing primary outcome data will be summarised by treatment arm and investigated through a sensitivity analysis. Full details of the planned methods of analysis and descriptive statistics are described in this paper. The NINJA study protocol has been published previously. DISCUSSION: The planned analysis strategy for the NINJA trial has been set out here to reduce the risk of reporting bias and data-driven analysis. Any deviations from the SHEAP described in this paper will be detailed and justified fully in the final report of the trial. TRIAL REGISTRATION: ISRCTN, ISRCTN44551796 . Registered on 23 April 2018.

Giant hemifacial plexiform neurofibroma arising from trigeminal ganglion.

We present a case of a massive hemifacial plexiform neurofibroma. The tumor arose from the right trigeminal ganglion in the middle cranial fossa, involving the 3 divisions of the trigeminal nerve. This affected the whole right side of the face. The principles of management are discussed.

Composite grafts for fingertip amputations: A systematic review protocol.

BACKGROUND: There is much debate in the hand surgery literature as to the management of fingertip amputations. Much research continues to be published in this area. Methods of reattachment include microsurgical and non-microsurgical (composite graft) replantation. The role of composite grafts lacks clarity in terms of outcomes, success rates and complications. Hence there is a need for an evidence synthesis, which can guide patient selection, the consent process and determine graft survival rates and functional outcomes to optimise patient outcomes. METHODS: Search of the databases OVID MEDLINE, PubMed, EMBASE, SCOPUS, The Cochrane Library and clinical trial registries from inception using terms "fingertip" "digital tip" "digit" "finger" "thumb" "amputation" "replantation" "reattachment" "reimplantation" and "composite graft" as key terms with "AND" selected as a Boolean operator, limited to humans will be conducted by two independent researchers. The patient population will include adults and children. Studies will be included if they report: (1) primary data; (2) outcomes of 'composite grafts' or 'nonmicrosurgical replantations'; (3) graft survival, (4) 5 or more cases. Articles will be excluded if surgical techniques involve: (1) composite graft pocketing, or (2) microsurgical replantation or (3) additional flaps (pulp or local). Full exclusion and inclusion criteria are described within this protocol. Data extraction will include; demographic details, patient comorbidities, amputation nature and level, functional, and aesthetic outcomes, complications and need for secondary procedures. All data extracted will be cross-checked, and discrepancies resolved through consensus. DISSEMINATION: This review will be published in a peer-reviewed journal and will be presented at national and international conferences to inform the practice of other clinicians.

NINJA trial: should the nail plate be replaced or discarded after nail bed repair in children? Protocol for a multicentre randomised control trial.

INTRODUCTION: Trauma to the nail bed is the most common surgically treated paediatric hand injury. The majority of surgeons replace the nail plate after repairing the nail bed despite a lack of evidence to do so. Replacing the nail plate may be associated with increased postoperative infection. We will investigate the impact of replacing or discarding the nail plate on infection, cosmetic appearance, pain and subsequent healthcare use. The Nail bed INJury Analysis trial (NINJA) aims to answer the question of whether the nail plate should be replaced or discarded after surgical nail bed repair in children. METHODS AND ANALYSIS: A two-arm parallel group open multicentre randomised control trial of replacing the nail plate or not, as part of a nail bed repair, will be undertaken in children presenting within 48 hours of a nail bed injury requiring surgical repair. The coprimary outcomes are: cosmetic appearance summary score at a minimum of 4 months and surgical site infection at around 7 days following surgery. Secondary outcomes are EuroQol EQ-5D-(Y); the pain intensity experienced at first dressing change; child/parent satisfaction with nail healing and healthcare resource use. We will recruit a minimum of 416 patients (208 in each group) over 3 years. Children and their parents/carers will be reviewed in clinic around 7 days after their operation and will be assessed for surgical site infection or other problems. The children, or depending on age, their parents/carers, will also be asked to complete a questionnaire and send in photos of their fingernail at a minimum of 4 months postsurgery to assess cosmetic appearance. ETHICS AND DISSEMINATION: The South Central Research Ethics Committee approved this study on 4 June 2019 (18/SC/0024). A manuscript to a peer-reviewed journal will be submitted on completion of the trial as per National Institute for Health Research publication policy. The results of this trial will substantially inform clinical practice and provide evidence on whether the practice of replacing the nail plate should continue at the time of nail bed repair. TRIAL REGISTRATION NUMBER: ISRCTN44551796.

Composite Grafts for Pediatric Fingertip Amputations: A Retrospective Case Series of 100 Patients.

BACKGROUND: Fingertip amputations are common. This study reports on the outcomes of composite grafts used for fingertip amputations in children, measuring graft take, predictors of graft take, complications, and patient-reported outcomes. METHODS: A retrospective case series of consecutive patients (≤ 16 years) undergoing composite grafts for fingertip amputations in a tertiary pediatric hospital, January 06 to December 16, was performed. Information was collected on amputations, graft take, and complications. Logistic regression was used to analyze factors predicting graft take (partial/complete or failure) including age; amputation level; mechanism and time delay to surgery. Patients were contacted via post or telephone to ask about functional and cosmetic outcomes and their perception of graft take. RESULTS: One hundred patients [57 (57%) males; mean age, 4.41 ± 3.98 years], presenting with 100 fingertip amputations, met the inclusion criteria. Amputation mechanism was crush in 75 (75%), avulsion in 13 (13%), and laceration in 12 (13%). Thirteen (13%) composite grafts survived completely, 46 (46%) partially, and 41 (41%) failed. Graft survival was higher in children under 4 years (P = 0.016). Seventeen (17%) grafts became infected, 9 (9%) required a reoperation, 9 (9%) had wound healing complications, and 4 (4%) patients developed psychological complications. Patient-reported survival was 33% higher than medical-reported survival. Cosmetic issues were the commonest complication reported by patients. Patients rated fingertips looking 3.5/5 normal, and that they were 4/5 satisfied with the appearance. Most patients were using their fingers normally by 2-6 months. CONCLUSIONS: Composite grafts for fingertip amputations mostly only partially survive, but morbidity is low, patient satisfaction is high, and acceptable cosmetic and functional outcomes are achieved.

WHO Safer Surgery checklist compliance amongst paediatric emergency plastic surgery patients in an UK hospital.

INTRODUCTION: The WHO Safer Surgery checklist has become an important component of perioperative safety. Our objective, was to determine the compliance of completing the checklist for paediatric emergency plastic surgery patients at our unit. METHODS: An initial baseline was performed with 70 patients over two months at our unit. Following this, we raised awareness at an audit meeting and closed the audit loop using 80 patients over two months. The audit is reported in line with SQUIRE 2.0 criteria. RESULTS: Initial compliance was 88% overall and this increased to 91% post-intervention. Compliance with the individual stages in both cycles was for sign-in: 85%-86%, for time-out 92%-98% and for sign-out 86%-89%. Around one in four checklists were not scanned in both periods. CONCLUSION: This audit showed a high overall level of compliance in the checklists that were scanned and available for scrutiny. We have identified the areas that most need improvement and suggest ways for doing so.

PHACE syndrome misdiagnosed as a port-wine stain.

We present the case of a boy born with a large macular, segmental vascular anomaly over the left face, initially diagnosed as a capillary malformation (port-wine stain) by the postnatal paediatric team. The vascular anomaly in the face then grew rapidly during the first few weeks of life and started to occlude the left eye, causing parental concerns about the infant's vision. A dermatological opinion established that the lesion was a segmental infantile haemangioma (IH). This, in combination with the posterior fossa malformation previously detected on antenatal scanning and confirmed by an MRI postnatally, satisfied the criteria for Posterior fossa abnormalities, Haemangiomas, Arterial abnormalities, Cardiac abnormalities and Eye abnormalities (PHACE) syndrome: a rare cutaneous neurovascular syndrome. This case highlights the diagnostic challenge posed by early phenotypes of haemangiomas as well as the importance of correctly diagnosing PHACE syndrome.

Nail bed INJury Assessment Pilot (NINJA-P) study: should the nail plate be replaced or discarded after nail bed repair in children? Study protocol for a pilot randomised controlled trial.

BACKGROUND: Nail bed injuries account for the majority of paediatric hand trauma cases. Despite their frequency, controversy remains regarding their treatment. The accepted teaching is to remove the fingernail, repair the underlying nail bed with fine sutures and replace the nail under the nail fold. A recent study by Miranda et al. (Plast Reconst Surg. 129(2):394e-396e, 2012) suggests that replacing the nail is associated with increased complications, in particular post-operative infection. Nail bed INJury Assessment Pilot (NINJA-P) is an external pilot study for a large pragmatic, multicentre, randomised, controlled study (NINJA) to assess whether the nail should be replaced or discarded after nail bed repair in children under the age of 16. METHODS/DESIGN: NINJA-P is a randomised pilot study. The participants are patients below 16 years of age who require surgical repair of the nail bed. Eligible patients will be randomised to receive one of two possible interventions. Group 1 will have the nail replaced after nail bed repair, and group 2 will have the nail discarded. The clinical outcome measures include the presence of post-operative complications at 2 weeks and 30 days, the cosmetic appearance of the nail at 4 months and the level of pain experienced by the child at their first dressings change at 2 weeks. In order to inform the design of the main NINJA trial, the following feasibility data will also be recorded: the number of potentially eligible children and the proportion which agree to take part in the study, the proportion of children who received the allocated treatment and reasons for any non-compliance and the proportion of participants with a valid response at each follow-up point. Neither the patient, family members nor treating physicians will be blinded. A replaced nail can take several weeks to fall off once a new nail has grown out. The cosmetic appearance of the nail at 4 months will be assessed by a blinded assessor. DISCUSSION: The NINJA-P pilot study will inform the design and execution of the NINJA trial, which will assess whether the nail should be replaced or discarded after nail bed repair in children under 16. It will provide randomised comparative evidence for the treatment of this common injury. TRIAL REGISTRATION: First participant randomised: 21/04/2015, UKCRN Portfolio ID: 18516, ISRCTN16571591.

Purinergic receptors are part of a signaling system for keratinocyte proliferation, differentiation, and apoptosis in human fetal epidermis.

We have investigated the expression of P2X5, P2X7, P2Y1, and P2Y2 receptor subtypes in 8- to 11-wk-old human fetal epidermis in relation to markers of proliferation (proliferating cell nuclear antigen (PCNA) and Ki-67), keratinocyte differentiation (cytokeratin K10 and involucrin), and markers of apoptosis (TdT-mediated dUTP nick end labeling (TUNEL) and anti-caspase-3). Immunohistochemistry showed that each of the four receptors was expressed in spatially distinct zones of the developing epidermis: P2Y1 receptors were found in the basal layer, P2X5 receptors were predominantly in the basal and intermediate layers, and both P2Y2 and P2X7 receptors were in the periderm. Colocalization experiments suggested different functional roles for these receptors. P2Y1 receptors were found in fetal keratinocytes positive for PCNA and Ki-67, suggesting a role in proliferation. P2X5 receptors double labeled with differentiated fetal keratinocytes that were positive for cytokeratin K10, suggesting a role in differentiation. P2X7 receptors colocalized with anti-caspase-3 antibody and were also expressed in periderm cells positive for TUNEL, suggesting a role in periderm cell apoptosis. P2Y2 receptors were found only in periderm cells and may have a role in chloride and fluid secretion into the amniotic fluid.

Purinergic receptors are part of a functional signaling system for proliferation and differentiation of human epidermal keratinocytes.

We investigated the expression of P2X5, P2X7, P2Y1 and P2Y2 receptor subtypes in normal human epidermis and in relation to markers of proliferation (PCNA and Ki-67), keratinocyte differentiation (cytokeratin K10 and involucrin) and markers of apoptosis (TUNEL and anticaspase-3). Using immunohistochemistry, we showed that each of the four receptors was expressed in a spatially distinct zone of the epidermis, suggesting different functional roles for these receptors. Functional studies were performed on primary cultures of human keratinocytes and on explanted rat skin, where different P2 receptor subtype agonists and antagonists were applied to cultured keratinocytes or injected subcutaneously into the skin, respectively. An increase in cell number was caused by low doses of the nonspecific P2 receptor agonist ATP, the P2Y2 receptor agonist UTP (p<0.001), and the P2Y1 receptor agonist 2MeSADP (p<0.05). There was a significant decrease in cell number as a result of treatment with the P2X5 receptor agonist ATPgammaS (p<0.001) and the P2X7 receptor agonist BzATP (p<0.001). Suramin caused a significant block in the effect of 100 microm ATP (p<0.01) and 1000 microm ATP (p<0.001) on cell number. These results imply that different purinergic receptors have different functional roles in the human epidermis with P2Y1 and P2Y2 receptors controlling proliferation, while P2X5 and P2X7 receptors control early differentiation, terminal differentiation and death of keratinocytes, respectively.

Expression of purinergic receptors in non-melanoma skin cancers and their functional roles in A431 cells.

We investigated the use of purinergic receptors as a new treatment modality for nonmelanoma skin cancers. Purinergic receptors, which bind adenosine 5'-tri-phosphate, are expressed on human cutaneous keratinocytes. Previous work in rat and human epidermis suggested functional roles for purinergic receptors in the regulation of proliferation, differentiation, and apoptosis. Immunohistochemical analysis of frozen sections in human basal cell carcinomas and squamous cell carcinomas for P2X5, P2X7, P2Y1, P2Y2, and P2Y4 receptors was performed, accompanied by detailed analysis of archive material of tumor subtypes in paraffin sections. Functional studies were performed using a human cutaneous squamous cell carcinoma cell line (A431), where purinergic receptor subtype agonists were applied to cells and changes in cell number were quantified via a colorimetric assay. Immunostaining in paraffin sections was essentially the same as that in frozen sections, although more detail of the subcellular composition was visible. P2X5 and P2Y2 receptors were heavily expressed in basal cell carcinomas and squamous cell carcinomas. P2X7 receptors were expressed in the necrotic center of nodular basal cell carcinomas and in apoptotic cells in superficial multifocal and infiltrative basal cell carcinomas, and squamous cell carcinomas. P2Y1 receptors were only expressed in the stroma surrounding tumors. P2Y4 receptors were found in basal cell carcinomas but not in squamous cell carcinomas. P2X5 receptors appear to be associated with differentiation. The P2X7 receptor agonist benzoylbenzoyl-adenosine 5'-triphosphate and high concentrations of adenosine 5'-triphosphate (1000-5000 microM) caused a significant reduction in A431 cell number (p<0.001), whereas the P2Y2 receptor agonist uridine 5'-triphosphate caused a significant amount of proliferation (p<0.001). We have demonstrated that non-melanoma skin cancers express functional purinergic receptors and that P2X7 receptor agonists significantly reduce cell numbers in vitro.