Sharpe B.,University of Bath |
Beresford M.,Royal United Hospital NHS Trust |
Bowen R.,Royal United Hospital NHS Trust |
Mitchard J.,Royal United Hospital NHS Trust |
Chalmers A.D.,University of Bath
Stem Cell Reviews and Reports | Year: 2013
The cancer stem cell hypothesis postulates that a single stem-like cancer cell is able to produce all cancer cell types found in a tumor. These cells are also thought to be the causative agents of relapse following therapy. In order to confirm the importance of cancer stem cells in tumor formation and patient prognosis, their role in prostate cancer must be comprehensively studied. This review describes current methods and markers for isolating and characterizing prostate cancer stem cells, including assays for self-renewal, multipotency and resistance to therapy. In particular the advantages and limitations of these approaches are analyzed. The review will also examine novel methods for studying the lineage of cancer stem cells in vivo using transgenic mouse models. These lineage tracing approaches have significant advantages and, if a number of challenges can be addressed, offer great potential for understanding the significance of cancer stem cells in human prostate cancer. © 2013 Springer Science+Business Media New York.
Willis J.,Royal United Hospital NHS Trust |
Willis J.,University of Bath |
Augustine D.,University of Oxford |
Shah R.,Gleneagles Medical Center |
And 2 more authors.
Journal of the American Society of Echocardiography | Year: 2012
Background: Despite the common practice of indexing left ventricular dimensions to body surface area, there remains a lack of indexed normal right ventricular (RV) two-dimensional caliper measurements. Variations in ranges for normal RV dimensions have been shown to exist, and indexing RV dimensions according to body surface area may help reduce this and provide a standardization useful for clinical practice. The aim of this study was to prospectively establish both absolute and indexed normal dimensions for the right ventricle using standardized positions in a multiethnic population. Furthermore, the effects of both gender and ethnicity on both the absolute and indexed results were also evaluated. Methods: Two hundred five healthy volunteers from four ethnic backgrounds (Indian, Chinese, Malay, and European) were prospectively enrolled and underwent two-dimensional echocardiography according to a set protocol. Ten measurements were made in conjunction with previous research. Intraobserver and interobserver and test-retest variability was assessed using coefficients of variation and intraclass correlation coefficients. Results: Male absolute results exceeded female absolute results in 90% of measurements (P =.003). European absolute results (male and female) were significantly larger in up to eight of 10 measurements (P =.01). When indexed, female results became significantly larger (P <.001) than male results. Indexing was able to reduce the number of statistical differences between male ethnic groups. Measurements showed good levels of intraobserver and interobserver variability for apical and short-axis measurements. Conclusions: Gender and body surface area play an important part in the determination of normal RV reference ranges, whereas ethnicity has little influence. Results using the suggested RV markers for these measurements showed good repeatability. Copyright 2012 by the American Society of Echocardiography.
Peden C.J.,Royal United Hospital NHS Trust |
Peden C.J.,Health Services Research Center |
Grocott M.P.W.,Health Services Research Center |
Grocott M.P.W.,University of Southampton |
Grocott M.P.W.,Southampton NIHR Respiratory Biomedical Research Unit
Anaesthesia | Year: 2014
Outcomes are essential measures of healthcare effectiveness and efficiency. Traditional measures of outcome, such as mortality and length of stay, are important and easy to measure but have significant limitations when evaluating the peri-operative care of elderly patients.alternative measures, including clinician-described (e.g. complication rates, functional status, frailty) and patient-reported outcome and experience measures, are important to provide a comprehensive description of peri-operative outcome in the older patient. However, few measurement tools have been developed or validated specifically for the elderly surgical patient. This paper describes the outcome measures currently in use, explores how they might be used to improve the quality of care provision, and indicates priority areas for perioperative outcomes research in the elderly surgical patients.©2013 The Association of Anaesthetists of Great Britain and Ireland.
Messenger D.E.,Royal United Hospital NHS Trust |
Driman D.K.,London Health Sciences Center |
Kirsch R.,University of Toronto
Human Pathology | Year: 2012
Venous invasion, or "large vessel" invasion, is a known independent prognostic indicator of distant recurrence and survival in colorectal cancer. Accurate assessment of venous invasion is of particular importance in stage II disease because it may influence the decision to administer adjuvant therapy. Venous invasion is widely believed to be an underreported finding with significant variability in its reported incidence. In the most recent College of American Pathologists' cancer reporting protocol, venous invasion is not recorded separately from lymphovascular, or "small vessel" invasion, which may not be appropriate because these features confer differing prognostic information. The presence of extramural venous invasion is strongly predictive of adverse outcome, although the prognostic significance of intramural venous invasion remains unknown. There are no formal guidelines regarding the pathologic assessment of venous invasion or the application of specific reporting criteria. The routine use of an elastic stain results in an almost 3-fold increase in the venous invasion detection rate when compared with a standard hematoxylin and eosin stain and may be a cost-effective means of increasing the diagnostic yield of venous invasion. The development of high-resolution magnetic resonance imaging, where extramural venous invasion can be detected preoperatively, may also influence the manner in which pathologists process specimens. This review focuses on recent developments in the assessment of venous invasion and highlights their potential impact on future practice. © 2012 Elsevier Inc. All rights reserved.
Cade S.C.,University College London |
Cade S.C.,Royal United Hospital NHS Trust |
Arridge S.,University College London |
Evans M.J.,Royal United Hospital NHS Trust |
Hutton B.F.,University College London
Medical Physics | Year: 2013
Purpose: Attenuation correction is essential for reliable interpretation of emission tomography, however, the use of transmission measurements to generate attenuation maps is limited by availability of equipment and potential mismatches between the transmission and emission measurements. The authors present a first step toward a method of estimating an attenuation map from measured scatter data without a transmission scan. Methods: A scatter model has been developed that accurately predicts the distribution of photons which have been scattered once. The scatter model has been used as the basis of a maximum likelihood gradient ascent method to estimate an attenuation map from measured scatter data. In order to estimate both the attenuation map and activity distribution, iterations of the derived scatter based algorithm have been alternated with the maximum likelihood expectation maximization algorithm in a joint estimation process. For each iteration of the attenuation map estimation, the activity distribution is fixed at the values estimated during the previous activity iteration, and in each iteration of the activity distribution estimation the attenuation map is fixed at the values estimated during the previous attenuation iteration. The use of photopeak data to enhance the estimation of the attenuation map compared to the use of scatter data alone has also been considered. The algorithm derived has been used to reconstruct data simulated for an idealized two-dimensional situation and using a physical phantom. Results: The reconstruction of idealized data demonstrated good reconstruction of both the activity distribution and attenuation map. The inclusion of information recorded in the photopeak energy window in the attenuation map estimation step demonstrated an improvement in the accuracy of the reconstruction, enabling an accurate attenuation map to be recovered. Validation of the results with physical phantom data demonstrated that different regions of attenuation could be distinguished in a real situation and produces results that represent a promising first step toward the use of scatter data to estimate the activity distribution and attenuation map from single photon emission tomography (SPECT) data without a transmission scan. Conclusions: The technique presented shows promise as a method of attenuation correction for SPECT data without the need for a separate transmission scan. Further work is required to further improve the method and to compensate for the assumptions used in the scatter model. © 2013 American Association of Physicists in Medicine.
Jaaback K.,Ward K3 John Hunter Hospital |
Johnson N.,Royal United Hospital NHS Trust |
Lawrie T.A.,Royal United Hospital
Cochrane Database of Systematic Reviews | Year: 2016
Background: Ovarian cancer tends to be chemosensitive and confine itself to the surface of the peritoneal cavity for much of its natural history. These features have made it an obvious target for intraperitoneal (IP) chemotherapy. Chemotherapy for ovarian cancer is usually given as an intravenous (IV) infusion repeatedly over five to eight cycles. Intraperitoneal chemotherapy is given by infusion of the chemotherapeutic agent directly into the peritoneal cavity. There are biological reasons why this might increase the anticancer effect and reduce some systemic adverse effects in comparison to IV therapy. Objectives: To determine if adding a component of the chemotherapy regime into the peritoneal cavity affects overall survival, progression-free survival, quality of life (QOL) and toxicity in the primary treatment of epithelial ovarian cancer. Search methods: We searched the Gynaecological Cancer Review Group's Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) Issue 2, 2011, MEDLINE (1951 to May 2011) and EMBASE (1974 to May 2011). We updated these searches in February 2007, August 2010, May 2011 and September 2015. In addition, we handsearched and cascade searched the major gynaecological oncology journals up to May 2011. Selection criteria: The analysis was restricted to randomised controlled trials (RCTs) assessing women with a new diagnosis of primary epithelial ovarian cancer, of any FIGO stage, following primary cytoreductive surgery. Standard IV chemotherapy was compared with chemotherapy that included a component of IP administration. Data collection and analysis: We extracted data on overall survival, disease-free survival, adverse events and QOL and performed meta-analyses of hazard ratios (HR) for time-to-event variables and relative risks (RR) for dichotomous outcomes using RevMan software. Main results: Nine randomised trials studied 2119 women receiving primary treatment for ovarian cancer. We considered six trials to be of high quality. Women were less likely to die if they received an IP component to chemotherapy (eight studies, 2026 women; HR = 0.81; 95% confidence interval (CI): 0.72 to 0.90). Intraperitoneal component chemotherapy prolonged the disease-free interval (five studies, 1311 women; HR = 0.78; 95% CI: 0.70 to 0.86). There was greater serious toxicity with regard to gastrointestinal effects, pain, fever and infection but less ototoxicity with the IP than the IV route. Authors' conclusions: Intraperitoneal chemotherapy increases overall survival and progression-free survival from advanced ovarian cancer. The results of this meta-analysis provide the most reliable estimates of the relative survival benefits of IP over IV therapy and should be used as part of the decision making process. However, the potential for catheter related complications and toxicity needs to be considered when deciding on the most appropriate treatment for each individual woman. The optimal dose, timing and mechanism of administration cannot be addressed from this meta-analysis. This needs to be addressed in the next phase of clinical trials. © 2016 The Cochrane Collaboration.
Miles T.,Royal United Hospital NHS Trust
Cochrane database of systematic reviews (Online) | Year: 2010
BACKGROUND: Many vaginal dilator therapy guidelines advocate routine vaginal dilation during and after pelvic radiotherapy to prevent stenosis (abnormal narrowing of the vagina). The UK Gynaecological Oncology Nurse Forum recommend dilation "three times weekly for an indefinite time period". The UK patient charity Cancer Backup advises using vaginal dilators from two to eight weeks after the end of radiotherapy treatment. Australian guidelines recommend dilation after brachytherapy "as soon as is comfortably possible" and "certainly within four weeks and to continue for three years or indefinitely if possible". However, dilation is intrusive, uses health resources and can be psychologically distressing. It has also caused rare but very serious damage to the rectum. OBJECTIVES: To review the benefits and harms of vaginal dilation therapy associated with pelvic radiotherapy for cancer. SEARCH STRATEGY: Searches included the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, Issue 4), MEDLINE (1950 to 2008), EMBASE (1980 to 2008) and CINAHL (1982 to 2008). SELECTION CRITERIA: Any comparative randomised controlled trials (RCT) or data of any type which compared dilation or penetration of the vagina after pelvic radiotherapy treatment for cancer. DATA COLLECTION AND ANALYSIS: The review authors independently abstracted data and assessed risk of bias. We analysed the mean difference in sexual function scores and the risk ratio for non-compliance at six weeks and three months in single trial analyses. No trials met the inclusion criteria. MAIN RESULTS: Dilation during or immediately after radiotherapy can, in rare cases, cause damage and there is no persuasive evidence from any study to demonstrate that it prevents stenosis. Data from one RCT showed no improvement in sexual scores in women who were encouraged to practice dilation. Two case series and one comparative study using historical controls suggest that dilation might be associated with a longer vaginal length but these data cannot reasonably be interpreted to show that dilation caused the change in the vagina. AUTHORS' CONCLUSIONS: Routine dilation during or soon after cancer treatment may be harmful. There is no reliable evidence to show that routine regular vaginal dilation during or after radiotherapy prevents the late effects of radiotherapy or improves quality of life. Gentle vaginal exploration might separate the vaginal walls before they can stick together and some women may benefit from dilation therapy once inflammation has settled but there are no good comparative supporting data.
Miles T.,Royal United Hospital NHS Trust |
Johnson N.,Royal United Hospital NHS Trust
The Cochrane database of systematic reviews | Year: 2014
MAIN RESULTS: We identified no studies for inclusion in the original review or for this update. However, we felt that some studies that were excluded warranted discussion. These included one randomised trial (RCT), which showed no improvement in sexual scores associated with encouraging women to practise dilation therapy; a recent small RCT that did not show any advantage to dilation over vibration therapy during radiotherapy; two non-randomised comparative studies; and five correlation studies. One of these showed that objective measurements of vaginal elasticity and length were not linked to dilation during radiotherapy, but the study lacked power. One study showed that women who dilated tolerated a larger dilator, but the risk of objectivity and bias with historical controls was high. Another study showed that the vaginal measurements increased in length by a mean of 3 cm after dilation was introduced 6 to 10 weeks after radiotherapy, but there was no control group; another case series showed the opposite. Three recent studies showed less stenosis associated with prophylactic dilation after radiotherapy. One small case series suggested that dilation years after radiotherapy might restore the vagina to a functional length.AUTHORS' CONCLUSIONS: There is no reliable evidence to show that routine, regular vaginal dilation during radiotherapy treatment prevents stenosis or improves quality of life. Several observational studies have examined the effect of dilation therapy after radiotherapy. They suggest that frequent dilation practice is associated with lower rates of self reported stenosis. This could be because dilation is effective or because women with a healthy vagina are more likely to comply with dilation therapy instructions compared to women with strictures. We would normally suggest that a RCT is needed to distinguish between a casual and causative link, but pilot studies highlight many reasons why RCT methodology is challenging in this area.BACKGROUND: Vaginal dilation therapy is advocated after pelvic radiotherapy to prevent stenosis (abnormal narrowing of the vagina), but can be uncomfortable and psychologically distressing.OBJECTIVES: To assess the benefits and harms of different types of vaginal dilation methods offered to women treated by pelvic radiotherapy for cancer.SEARCH METHODS: Searches included the Cochrane Central Register of Controlled Trials (CENTRAL 2013, Issue 5), MEDLINE (1950 to June week 2, 2013), EMBASE (1980 to 2013 week 24) and CINAHL (1982 to 2013).SELECTION CRITERIA: Comparative data of any type, which evaluated dilation or penetration of the vagina after pelvic radiotherapy treatment for cancer.DATA COLLECTION AND ANALYSIS: Two review authors independently assessed whether potentially relevant studies met the inclusion criteria. We found no trials and therefore analysed no data.
Johnson N.,Royal United Hospital NHS Trust
Cochrane database of systematic reviews (Online) | Year: 2011
Endometrial adenocarcinoma (womb cancer) is a malignant growth of the lining (endometrium) of the womb (uterus). It is distinct from sarcomas (tumours of the uterine muscle). Survival depends the risk of microscopic metastases after surgery. Adjuvant (postoperative) chemotherapy improves survival from some other adenocarcinomas, and there is evidence that endometrial cancer is sensitive to cytotoxic therapy. This systematic review examines the effect of chemotherapy on survival after hysterectomy for endometrial cancer. To assess efficacy of adjuvant (postoperative) chemotherapy for endometrial cancer. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2010, Issue 3), MEDLINE and EMBASE up to August 2010, registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Randomised controlled trials (RCTs) comparing adjuvant chemotherapy with any other adjuvant treatment or no other treatment. We used a random-effects meta-analysis to assess hazard ratios (HR) for overall and progression-free survival and risk ratios (RR) to compare death rates and site of initial relapse. Five RCTs compared no additional treatment with additional chemotherapy after hysterectomy and radiotherapy. Four trials compared platinum based combination chemotherapy directly with radiotherapy. Indiscriminate pooling of survival data from 2197 women shows a significant overall survival advantage from adjuvant chemotherapy (RR (95% CI) = 0.88 (0.79 to 0.99)). Sensitivity analysis focused on trials of modern platinum based chemotherapy regimens and found the relative risk of death to be 0.85 ((0.76 to 0.96); number needed to treat for an additional beneficial outcome (NNT) = 25; absolute risk reduction = 4% (1% to 8%)). The HR for overall survival is 0.74 (0.64 to 0.89), significantly favouring the addition of postoperative platinum based chemotherapy. The HR for progression-free survival is 0.75 (0.64 to 0.89). This means that chemotherapy reduces the risk of being dead at any censorship by a quarter. Chemotherapy reduces the risk of developing the first recurrence outside the pelvis (RR = 0.79 (0.68 to 0.92), 5% absolute risk reduction; NNT = 20). The analysis of pelvic recurrence rates is underpowered but the trend suggests that chemotherapy may be less effective than radiotherapy in a direct comparison (RR = 1.28 (0.97 to 1.68)) but it may have added value when used with radiotherapy (RR = 0.48 (0.20 to 1.18)). Postoperative platinum based chemotherapy is associated with a small benefit in progression-free survival and overall survival irrespective of radiotherapy treatment. It reduces the risk of developing a metastasis, could be an alternative to radiotherapy and has added value when used with radiotherapy.
Nash K.C.M.,Royal United Hospital NHS Trust
Reviews in Clinical Gerontology | Year: 2012
The proportion of older people becoming frail will increase with the expanding older population. Apart from poor health, frailty is associated with loss of strength and functional dependency. Building on previous work in this area, this review investigates the effectiveness, sustainability and adverse effects of exercise interventions on muscle strength and physical performance in frail older people. Randomized controlled trials reporting physical outcomes in frail older people were identified from seven electronic databases. Thirteen trials involving 1652 participants met the inclusion criteria. There was wide heterogeneity in degree of frailty, types of intervention, outcome measures and results. However, evidence from this review suggests that exercise and some physical activity programmes, particularly moderate intensity and multi-component programmes, are safe and can improve strength and function in the majority of frail older people except highly frail individuals with multiple co-morbidities. There was limited evidence on transferability of improvements into everyday life, and sustainability could not be determined. © Copyright 2012 Cambridge University Press.