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The pressures on the dental team to successfully manage and treat periodontal diseases in general practice are ever-mounting. Dental practitioners have a duty of care to screen, investigate, diagnose, risk assess and appropriately treat periodontal diseases using evidence-based practice. Once patients are stable, they must continue to monitor and risk assess patients in the maintenance phase. Managing periodontal diseases in general practice is challenging and this has been reflected in the rising trend in periodontal litigation. General practitioners see the complete spectrum of patients; from those wanting to improve their oral health and are motivated to do so, to those who do not want to improve and are unmotivated. The Healthy Gums DO Matter toolkit, developed by Greater Manchester Local Professional Network for dentistry, provides a framework for dental teams on how to manage and treat periodontal diseases in general practice, providing a more pragmatic approach working under the current NHS dental contract. A care pathway model has been developed to manage both engaging and non-engaging patients, allowing for an increased focus on oral health education, patient motivation, personalised oral care plans and behaviour change techniques to achieve better outcomes for patients.

Objectives: The objective of the present study was to examine the grey value parameters and their magnitudes produced by CBCT and whether they are influenced by different scanners with various scanning conditions., Methods: An ATOM Max dental and diagnostic artificial head was scanned by two CBCT scanners (Planmeca and iCAT). Under full field of view with normal dose and ultralow-dose (ULD) conditions, the Planmeca scanner was examined for three scanning resolutions (200, 400, and 600 micron voxel sizes) and the iCAT scanner was tested for four scanning resolutions (200, 250, 300 and 400 micron voxel sizes). After 9 weeks, the artificial head was scanned again by the Planmeca scanner with the same scanning conditions. In addition, two hydroxyapatite phantoms (1220 and 1540 mg cm -3 ) were adhered on the artificial head and scanned using normal and ULD scanning conditions of 400 micron voxel size with both scanners. The grey value histogram of each region, which is proportional to the bone mineral density (BMD) histogram, was utilized to determine grey value distribution parameters and compare scanners (ANOVA, p < 0.05)., Results: The different scanning conditions and the bilateral locations of the artificial head did not have significant effects on measurements of the grey value parameters (p > 0.436) with excellent repeatability. However, the iCAT scanner produced significantly different grey values from the Planmeca scanner (p < 0.001)., Conclusions: CBCT can assess BMD, while calibration of absolute measures is necessary to obtain comparable values between different scanners that are currently used to assess oral bone quantity and quality.

The Health and Social Care Act 2012 heralded wide reaching reforms intended to place clinicians at the heart of the health service. For NHS general dental practice, the conduits for this clinical leadership are the NHS England local professional networks. In Greater Manchester, the local professional network has developed and piloted a clinician led quality improvement project: 'Healthy Gums DO Matter, a Practitioner's Toolkit'. Used as a case study, the project highlighted the following facilitators to clinical leadership in dentistry: supportive environment; mentoring and transformational leadership; alignment of project goals with national policy; funding allowance; cross-boundary collaboration; determination; altruism; and support from wider academic and specialist colleagues. Barriers to clinical leadership identified were: the hierarchical nature of healthcare, territorialism and competing clinical commitments.

Androgen receptor (AR) signaling in stromal cells is important in prostate cancer, yet the mechanisms underpinning stromal AR contribution to disease development and progression remain unclear. Using patient-matched benign and malignant prostate samples, we show a significant association between low AR levels in cancer associated stroma and increased prostate cancer-related death at one, three and five years post-diganosis, and in tissue recombination models with primary prostate cancer cells that low stromal AR decreases castration-induced apoptosis. AR-regulation was found to be different in primary human fibroblasts isolated from adjacent to cancerous and non-cancerous prostate epithelia, and to represent altered activation of myofibroblast pathways involved in cell cycle, adhesion, migration, and the extracellular matrix (ECM). Without AR signaling, the fibroblast-derived ECM loses the capacity to promote attachment of both myofibroblasts and cancer cells, is less able to prevent cell-matrix disruption, and is less likely to impede cancer cell invasion. AR signaling in prostate cancer stroma appears therefore to alter patient outcome by maintaining an ECM microenvironment inhibitory to cancer cell invasion. This paper provides comprehensive insight into AR signaling in the non-epithelial prostate microenvironment, and a resource from which the prognostic and therapeutic implications of stromal AR levels can be further explored.

Pancreatic lymphoepithelial cysts are more common in men, can occur anywhere in the pancreas, are sharply demarcated from surrounding tissues, and range in size from 1.2 to 17 cm. Patients are usually middle aged, presenting symptoms include abdominal pain, nausea, vomiting, and diarrhea, although many tumors are asymptomatic and are discovered incidentally on organ imaging or at autopsy. An elevated serum carbohydrate-associated antigen 19-9 may wrongly suggest a mucinous neoplasm. The diagnosis can be made preoperatively with a combination of organ imaging, fine needle aspiration biopsy, or ultrasound-guided Trucut biopsies. Cysts can be unilocular, bilocular, or multilocular, have walls up to 0.6 cm thick which are lined by squamous epithelium, occasional columnar mucinous cells, and small foci of sebaceous cells. The epithelium is surrounded by a dense rim of lymphoid tissue with scattered lymphoid follicles. Invaginations of the epithelium into the lymphoid tissue, reminiscent of a Warthin tumor, are occasionally observed. The pathogenesis is unknown. Pancreatic lymphoepithelial cysts are cured by conservative resection but if they are asymptomatic and are diagnosed before surgery, no treatment is necessary.

Background: Tamoxifen has been shown to promote the growth of human endometrial tumors implanted in athymic mice, and it has been associated with a twofold to threefold increase in endometrial cancer. Toremifene, a chlorinated derivative of tamoxifen, and ICI 182,780, a pure antiestrogen, are two new antiestrogens being developed for the treatment of breast cancer. The effects of these drugs on endometrial cancer are currently unknown. Our objective was to evaluate the effects of toremifene and ICI 182,780 on the growth of human endometrial cancer in athymic mice., Methods: Athymic, ovariectomized mice were implanted with human endometrial tumors and treated with estrogen, tamoxifen, or the new antiestrogens., Results: The effects of tamoxifen and toremifene on the growth of either tamoxifen-stimulated or tamoxifen-naive endometrial tumors in athymic mice were not substantially different. ICI 182,780 inhibited the growth of tamoxifen-stimulated endometrial cancer, in both the presence and the absence of estrogen., Conclusions: Toremifene and tamoxifen produce identical effects in our endometrial cancer models. Therefore, it is possible that toremifene, like tamoxifen, may be associated with an increased incidence of endometrial cancer. In contrast, ICI 182,780 inhibited tamoxifen-stimulated endometrial cancer, both in the presence and in the absence of estrogen, suggesting that this drug may be safe with regard to the endometrium, even if it is used following tamoxifen, and that it may not result in an increased incidence of endometrial cancer. Indeed, it is even possible that ICI 182,780 may prove useful as an adjuvant agent in early stage endometrial cancer.

It is clear that growth of the MCF-7 breast cancer cell line is stimulated by estrogen and when estrogen is removed, growth slows. We have observed a tumor derived from MCF-7 cells that grows in athymic mice in the absence of estrogen stimulation. We hypothesized that a mutation in the estrogen receptor (ER) could be responsible for this constitutive growth. Using single stranded conformational polymorphism (SSCP) and DNA sequencing analysis, we have identified an ER containing a point mutation at position 415 (gly to val) within the hormone binding domain. The functional activity of this mutant was assessed in vitro and in vivo. Using transient transfection into an ER negative breast cancer cell with an ERE luciferase reporter gene, we found that both the wild-type and mutant receptors have similar efficacy. Additionally, the estrogenic responses were blocked by antiestrogens in a concentration related manner. We also found that tumors with the mutant receptor show similar growth response in athymic mice as wild-type: stimulation with estradiol and inhibition with antiestrogens. We conclude that the point mutation at position 415 (gly to val) is not responsible for constitutive growth.

Laboratory models for breast and endometrial cancer have had an enormous impact on the clinical development of antiestrogens. Results from the DMBA-induced rat mammary cancer model has provided the scientific principles required to evaluate long-term adjuvant tamoxifen therapy. Similarly, the athymic mouse model allowed the identification of clinically relevant mechanisms of drug resistance to tamoxifen and a model system to test new agents for cross resistance. Additionally, the endometrial cancer model has allowed the identification of agents that cause a slight increase in the risk of endometrial cancer long before the data would have be available from clinical studies. However, it should be stressed that this model is really only relevant for agents to be tested as preventives in normal women. The risks of developing endometrial cancer during tamoxifen therapy are slight compared with the survival benefit in controlling breast cancer.Finally the discovery of the carcinogenic potential of tamoxifen in the rat liver, 20 years after it was first introduced into clinical practice, raises an interesting issue. If the studies of liver carcinogenicity had been completed and published in the early 1970's there would be no tamoxifen and tens of thousands of women with breast cancer would have died prematurely. In fact there would have been no incentive to develop new agents as alternatives to tamoxifen or following tamoxifen failure. Most importantly, we would not have any knowledge about the target-site or selective actions of antiestrogens. All the current interest in selective estrogen receptor modulators (SERMs) is based on the huge clinical data base obtained by studying tamoxifen. The success of tamoxifen as an agent that preserves bone density, lowers cholesterol and prevents contralateral breast cancer(43) has become a classic example of a multimechanistic drug. These concepts have acted as a catalyst to develop new agents for new applications. The laboratory studies of raloxifene(44-46)) provided the scientific rationale for the use of raloxifene as a preventive for osteoporosis(47)) but with the goal of preventing breast cancer in post-menopausal women(48,49)) (Fig 5). It is clear that the close collaboration between laboratory and clinical research has revolutionized the prospects for women's health care in the 21st century.

Tamoxifen is the endocrine therapy of choice for all stages of breast cancer. However, the drug cannot be considered to be a cure as drug resistance will eventually develop. The resistance can take two forms: either the loss of estrogen receptor or the selection of estrogen receptor positive disease that is tamoxifen stimulated for growth. Laboratory studies have demonstrated that tamoxifen-stimulated MCF-7 breast tumors can develop in athymic mice. A number of pure (nonestrogenic) antiestrogens have been discovered that can either be administered by injection (e.g., ICI 182,780) or orally (e.g., EM-800). In preliminary clinical studies, the compound ICI 182,780 (Faslodex) has been shown to be an effective second-line therapy after tamoxifen failure. The goal of future clinical studies is to evaluate the therapeutic efficacy and patient acceptability of aromatase inhibitors (postmenopausal estrogen withdrawal), and injectable or oral pure antiestrogens after the failure of long-term tamoxifen therapy. Clearly, the primary purpose for the treatment of advanced breast cancer is to control disease growth; nevertheless, an evaluation of the effect of new agents on bones and lipids is required before pure antiestrogens could be considered for adjuvant therapy.