Epidemiology of basal and cutaneous squamous cell carcinoma in the U.K. 2013-15: a cohort study.

BACKGROUND: Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), together known as keratinocyte cancers (KCs), are the commonest cancer in white ethnic populations. Recent improvements to registry data collection in England has allowed more accurate analysis of the epidemiology of BCC and cSCC and for the first time we are able to provide an accurate (representative) tumour burden for KC in the U.K. OBJECTIVES: To estimate the incidence of BCC and cSCC in the U.K. METHODS: A cohort of patients with KCs between 2013 and 2015 were identified using linkage to diagnostic codes derived from pathology reports collected into the national cancer registry. Data from England's cancer registry were combined with data from Scotland, Northern Ireland and Wales. European age-standardized incidence rates (EASRs) of the first BCC and cSCC per patient per annum (PPPA) were calculated. RESULTS: In the U.K, the EASR of the first BCC and cSCC PPPA in 2013-15 were 285 and 77 per 100 000 person years, respectively (211 120 KCs total in 2015). The mean annual percentage increase was 5% between 2013 and 2015 for both BCC and cSCC. By counting the first KC PPPA, we include an additional 51% KCs compared with the previous reporting technique which counts only the first BCC and cSCC in a patient's lifetime, yet it represents a probable underestimation of 5-11% of the true tumour count. CONCLUSIONS: Based on an improved methodology, a more representative incidence of KC is presented, which is essential to healthcare planning and will lead to improved understanding of the epidemiology of KC. What's already known about this topic? Keratinocyte cancers (KCs) are the most common cancers affecting white ethnic populations. The incidence of basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) is increasing worldwide including the U.K., most commonly in elderly male Caucasian patients. These cancers are traditionally substantially underreported and frequently excluded from national cancer statistics. What does this study add? Using improved data collection methods in England and validated tumour-reporting techniques, we report the most accurate BCC and cSCC incidence data for the U.K. ever published. Identifying the first BCC and cSCC per patient per annum, the incidence of BCC and cSCC in the U.K. (excluding Wales) was 285 and 77 per 100 000 person years, respectively, between 2013 and 2015, with more than 210 000 KCs in the U.K. in 2015.

Organisation of Prostate Cancer Services in the English National Health Service.

AIMS: The National Prostate Cancer Audit (NPCA) started in April 2013 with the aim of assessing the process of care and its outcomes in men diagnosed with prostate cancer in England and Wales. One of the key aims of the audit was to assess the configuration and availability of specialist prostate cancer services in England. MATERIALS AND METHODS: In 2014, the NPCA undertook an organisational survey of all 143 acute National Health Service (NHS) Trusts and 48 specialist multidisciplinary team (MDT) hubs cross England. Questionnaires established the availability and location of core diagnostic, treatment and patient-centred support services for the management of non-metastatic prostate cancer in addition to specific diagnostic and treatment procedures that reflect the continuing evolution of prostate cancer management, such as high-intensity focused ultrasound (HIFU) and stereotactic body radiotherapy. RESULTS: The survey received a 100% response rate. The results showed considerable geographical variation with respect to the availability of core treatment modalities, the size of the target population and catchment areas served by specialist MDT hubs, as well as in the uptake of additional procedures and services. Specifically there are gaps in the availability of core radiotherapy procedures; high dose rate and low dose rate brachytherapy are available in 44% and 75% of specialist MDTs, respectively. By comparison, there seems to be a relative 'over-penetration' of surgical innovation, with 67% of specialist MDTs providing robotic-assisted laparoscopic prostatectomy and 21% HIFU. There is also evidence of increased centralisation of core surgical procedures and regional inequity in the availability of surgical innovation across England. CONCLUSIONS: The organisational survey of the NPCA has provided a comprehensive assessment of the structure and function of specialist MDTs in England and the availability of prostate cancer procedures and services. As part of the prospective audit, the NPCA will assess the effect of the availability of prostate cancer services on access regionally and subsequent outcomes of care according to evidence-based guidelines.

Primary and isolated anaplastic large cell lymphoma of the bone marrow.

Anaplastic large cell lymphoma (ALCL) is a T-cell lymphoma in which the majority of patients present with advanced stage III or IV disease. Here we report a case of ALCL where bone marrow was the only site of disease, in a 60-year-old man with pyrexia and pancytopenia. The diagnosis of ALCL was made on detection of CD30-positive anaplastic cells in the bone marrow, together with prominent hemophagocytosis. Genetics confirmed the clonal nature of the disease and showed it to be anaplastic lymphoma kinase (ALK) negative. Primary isolated bone marrow ALCL should be considered in the diagnosis of pancytopenia associated with hemophagocytosis.

Osteoclastic tartrate-resistant acid phosphatase (Acp 5): its localization to dendritic cells and diverse murine tissues.

Tartrate-resistant acid phosphatase (TRAP) is a histochemical marker of the osteoclast. It is also characteristic of monohistiocytes, particularly alveolar macrophages, and is associated with diverse pathological conditions, including hairy cell leukemia and AIDS encephalopathy. To study the biology of this enzyme, we investigated its expression and activity in mouse tissues. Confocal fluorescence studies showed that TRAP is localized to the lysosomal compartment of macrophages. In adult mice, high activities of the enzyme were demonstrated in bone, spleen, liver, thymus, and colon, with lower amounts in lung, stomach, skin, brain, and kidney. Trace amounts were detected in testis, muscle, and heart. Expression of TRAP mRNA was investigated in tissue sections by in situ hybridization and protein expression was monitored by histochemical staining or immunohistochemically. TRAP is widely expressed in many tissues, where it is associated with cells principally originating from the bone marrow, including those of osteoclast/macrophage lineage. The cellular distribution of TRAP mRNA and enzyme antigen in the tissues corresponds closely to that of cells staining with an antibody directed to the CD80 (B7) antigen. Therefore, to confirm its putative localization in dendritic cells, isolated bone marrow dendritic cells were matured in culture. These co-stained strongly for TRAP protein and the CD80 antigen. These studies demonstrate that TRAP is a lysosomal enzyme that is found in diverse murine tissues, where it is expressed in dendritic cells as well as osteoclasts and macrophages, as previously shown. (J Histochem Cytochem 48:219-227, 2000)

The biological toolbox: a computer program for simulating basic biological and pathological processes.

The program described here has been written to enable pathologists and biologists with almost no computer experience to design complex models of cell interactions. The program although simulating in only two dimensions allows the user to define the individual rules governing cell behaviour using a language called Cell Description Language, then simulates the multiple interactions between the cells to produce a dynamic visual interpretation representing tissue growth and differentiation. The program has been developed using the World Wide Web, thereby giving access to anyone with an Internet connection. The Web technology allows others to use our powerful computers to perform the complex calculations that are necessary and effectively eliminates the problems of modifying and compiling the program to run on more than one hardware platform. The changes that take place during the simulation are presented as a video using the MPEG video format; they may then be viewed on many different types of computers. The toolbox provides a novel approach to computer-based biological simulations and an excellent resource for teaching.

A population-based validation of the prognostic model PREDICT for early breast cancer.

INTRODUCTION: Predict (www.predict.nhs.uk) is a prognostication and treatment benefit tool developed using UK cancer registry data. The aim of this study was to compare the 10-year survival estimates from Predict with observed 10-year outcome from a British Columbia dataset and to compare the estimates with those generated by Adjuvant! (www.adjuvantonline.com). METHOD: The analysis was based on data from 3140 patients with early invasive breast cancer diagnosed in British Columbia, Canada, from 1989-1993. Demographic, pathologic, staging and treatment data were used to predict 10-year overall survival (OS) and breast cancer specific survival (BCSS) using Adjuvant! and Predict models. Predicted outcomes from both models were then compared with observed outcomes. RESULTS: Calibration of both models was excellent. The difference in total number of deaths estimated by Predict was 4.1 percent of observed compared to 0.7 percent for Adjuvant!. The total number of breast cancer specific deaths estimated by Predict was 3.4 percent of observed compared to 6.7 percent for Adjuvant! Both models also discriminate well with similar AUC for Predict and Adjuvant! respectively for both OS (0.709 vs 0.712) and BCSS (0.723 vs 0.727). Neither model performed well in women aged 20-35. CONCLUSION: In summary Predict provided accurate overall and breast cancer specific survival estimates in the British Columbia dataset that are comparable with outcome estimates from Adjuvant! Both models appear well calibrated with similar model discrimination. This study provides further validation of Predict as an effective predictive tool following surgery for invasive breast cancer.

The impact of information technology on histopathology.

Pathology is one of the most computer intensive areas of medicine and as a result diagnostic pathologists in histopathology have often been at the cutting edge of computer literacy. The majority of laboratories use laboratory information systems to issue and store pathology reports. Many of these systems provide the diagnostician with the ability to retrieve reports and cases using coding systems such as SNOMED, but more advanced computer facilities that might assist the pathologist in the diagnosis or interpretation of a case are often lacking. In recent years advances in computer technology have begun to have a much wider impact on the practice of medicine and newer technologies are beginning to find their way into the reporting room. In this review, I cover some of the recent and emerging advances in IT that have the potential to revolutionize the practice of diagnostic histopathology in the next 5 years. The major area of telepathology has been a subject of several recent reviews and will not be covered here.

A networked computer program for managing a national external quality assurance scheme in cytopathology.

We described a computer program to manage a national external quality assurance (EQA) scheme in cytopathology which uses the international computer network, the Internet, to collect data directly from participants, thereby reducing errors of transcription and administrative costs. Feedback to screeners and pathologists is provided as high quality images of the diagnostic areas on the slide which are only available once all users at a centre have entered their answers. This allows comparison with the original material while it is still available at this site. Users are encouraged to register differences of opinion by labelling areas on images of the slides on the computer. The program performs the statistical analysis of the data for each centre and each slide.

Legal and ethical issues in the use of anonymous images in pathology teaching and research.

The privacy of patients' health information is of paramount importance. However, it is equally important that medical staff and students have access to photographs and video recordings of real patients for training purposes. Where the patient can be identified from such images, his or her consent is clearly required to both obtain the image and to use it in this way. However, the need for consent, both legally and ethically, is much less convincing where the patient cannot, by the very nature of the image, be identified from it. This is the case for many images used in the teaching of clinical medicine, such as videos taken of laparoscopies, images of internal organs and unlabelled X-rays.

The DNA-binding protein E12 co-operates with XMyoD in the activation of muscle-specific gene expression in Xenopus embryos.

Two alternatively spliced products of the human E2A gene, E12 and E47, encode helix-loop-helix DNA-binding proteins. Here we describe the isolation of two Xenopus cDNAs; one, XE12, is structurally similar to human E12 and the other contains a sequence similar to E47. Transcripts of both cDNAs are present at all the stages of Xenopus development tested and in all regions of the embryo. The DNA binding properties of in vitro translated XE12 are indistinguishable from those of human E12. We have shown previously that an embryonic muscle DNA-binding activity, EMF1, that binds to a promoter sequence required for the expression of the cardiac actin gene, contains the Xenopus myogenic factor XMyoD. Here we show that it also contains protein that interacts with an anti-E12 antiserum, suggesting that XE12 and XMyoD proteins, or very similar ones, are present in EMF1. We have addressed the functional role of XE12 in muscle gene transcription in Xenopus embryos by injecting in vitro synthesized RNA into the two cell embryo. Overexpression of XE12 and XMyoD augments by greater than 10-fold the ectopic activation of the endogenous cardiac actin gene that can be produced by XMyoD alone. Our DNA binding results strongly suggest that this effect is mediated through a direct interaction of the XE12-XMyoD complex with specific sites in the cardiac actin promoter. We suggest that XE12 is functionally important in muscle gene activation in embryonic development.

The use of a computer model to simulate epithelial pathologies.

The complexity of the interactions of the many rules governing cell behaviour and the changes that lead to the pathological features seen in disease is such that linking cause and effect can be very difficult. However, the use of computers to model normal biological and pathological processes provides a powerful technique for studying the effects of the interactions of a variety of biological rules. Such an approach is strengthened by using a graphical display that simulates the organization of cells in a tissue. Skin, and specifically the epidermis, is characterized by a regular morphology and the ability to regenerate itself throughout adult life and there are considerable biological data available on the normal and pathological process that affect this organ. A model of normal skin has been developed which shows a structure similar to normal epidermis and is capable of healing itself if damaged. This paper describes the effects on the overall structure of introducing mutations to individual rules in the model. Changes that alter cell proliferation or differentiation are introduced and the effects that these produce are compared with epidermal pathologies. Even a simple model is capable of producing insights into the types of events that may occur in a variety of dermatopathological conditions.

A computer graphic simulation of squamous epithelium.

An epithelium maintains its integrity through the organized growth and orderly differentiation of a transient cell population derived from stem cells. This organization is dependent upon both physical mechanisms such as cell adhesion and attraction and the relationship between differentiation and cell division. The interactions between these processes are complex and difficult to conceptualize from a purely mathematical approach. We have therefore set out to develop a graphic model of an epithelium controlled by rules that can be modified. We have chosen to model epidermis, the most superficial part of skin, with cells differentiating from a stem cell population and being lost from the surface of the model. The model is novel not only in the rules that govern cell behaviour, but also because it does not require a predefined lattice to assign the position of cells. Each cell assumes a position depending upon the balance of adhesive and repulsive forces that it experiences. Chemical factors which affect the differentiation of individual cell types are assumed to be produced both by cells within the model and externally from the underlying connective tissue. These "chemical factors" diffuse through the model with a concentration that declines as an inverse square with distance from the source. The rules allow the model to grow from a single stem cell to reach a steady state. At steady state the pattern and clonal structure is strikingly similar to that seen in a range of normal epithelia. Furthermore, if part of the model is removed it is capable of regenerating itself without additional rules. The model allows the visualization of the effects of introducing new rules and modifying the interaction between chosen rules. This study demonstrates that a set of simple rules can be used to make a dynamic flexible model resembling skin.

The development and evaluation of the UK national telepathology network.

AIMS: As technology advances and costs fall, it may be anticipated that soon every histopathologist will expect to be able to exchange electronic images with colleagues. Arguing that the value of a network increases as more people are connected, we sought to install a simple, low-cost telepathology system into any histopathology laboratory which requested it within the UK. METHODS AND RESULTS: We assumed that laboratories had microscopes, computers and internet access. We offered low-cost video cameras, video input cards, software and training to any histopathology department requesting installation, limited only by resources supplied by the UK government. We also established central servers and a website with 'help' files. After 1 year we studied system use and pathologists' opinions by circulating a questionnaire. Installations were completed in 35 laboratories; there are currently 66 registered users of the system, with 16 identified 'experts' covering most organ systems. Serious difficulties were caused by institutional firewalls and reluctance of local information technology (IT) staff to make changes to facilitate the installation or to help resolve subsequent network problems. After installation, many of the telepathology systems remain unused. Concerns were expressed about image quality, though mainly by pathologists who had not used the system for diagnostic work. The system remains available, but the level of use is low. CONCLUSIONS: This project has not achieved its aims. The reasons are complex, but mainly relate to human attitudes. Pathologists with excessive workloads were reluctant to use time to learn new skills which were not directed to reducing workload. IT staff did not perceive the project as part of their routine work. There were also numerous technological problems, but although image quality was cited by many, it was not a complaint of those who actively used the system. These problems have not been encountered by previous projects which involved small groups of committed enthusiasts.