Critique of fourier transform infrared microspectroscopy applications to prostate pathology diagnosis

Prostate cancer is a biologically heterogenous disease with considerable variation in clinical aggressiveness. Gleason grade, the universally accepted method for classification of prostate cancer, is subjective and gives limited predictive information regarding prostate cancer progression. There is a clinical need for an objective, reliable tool to help pathologists improve current prostate tissue analysis methods and better assess the malignant potential of prostate tumours. Fourier Transform Infrared (FTIR) microspectroscopy is a powerful bioanalytical technique that uses infrared light to interrogate biological tissue. The studies detailed in this thesis examine the ability of FTIR combined with multivariate analysis to discriminate between benign, premalignant and malignant prostate pathology in snap frozen, paraffinated and deparaffinated tissue. Prostate tissue was collected during and after urological procedures performed between 2005 and 2008. The tissue was analysed utilising a bench top FTIR system in point and image mapping modes. The histology under interrogation was identified by a uro- pathologist. Multivariate analysis was applied to the spectral dataset obtained. FTIR performance was evaluated. FTIR was able to reproducibly discriminate between benign and malignant prostate tissue in a pilot study. Cross validated diagnostic algorithms, constructed from the spectral dataset in this experiment, achieved sensitivities and specificities of 95% and 89% respectively. FTIR analysis of transverse paraffinated and deparaffinated radical prostatectomy sections achieved good differentiation of the benign, premalignant and malignant pathology groups. However the performance of diagnostic algorithms constructed from this dataset under cross validation was poor. The work in this thesis illustrates the potential of FTIR to provide an objective method to assist the pathologist in the assessment of prostate samples. The limitations of the technique and directions for future work are presented.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Study protocol for two pilot randomised controlled trials aimed at increasing physical activity using electrically assisted bicycles to enhance prostate or breast cancer survival

BACKGROUND: In 2020, 1.4 and 2.3 million new cases of prostate cancer and breast cancer respectively were diagnosed globally. In the UK, prostate cancer is the most common male cancer, while breast cancer is the most common female cancer. Engaging in physical activity (PA) is a key component of treatment. However, rates of PA are low in these clinical populations. This paper describes the protocol of CRANK-P and CRANK-B, two pilot randomised controlled trials, involving an e-cycling intervention aimed at increasing PA in individuals with prostate cancer or breast cancer respectively.METHODS: These two trials are single-centre, stratified, parallel-group, two-arm randomised waitlist-controlled pilot trials in which forty individuals with prostate cancer (CRANK-P) and forty individuals with breast cancer (CRANK-B) will be randomly assigned, in a 1:1 allocation ratio, to an e-cycling intervention or waitlist control. The intervention consists of e-bike training with a certified cycle instructor, followed by the provision of an e-bike for 12 weeks. Following the intervention period, participants in the e-bike condition will be directed to community-based initiatives through which they can access an e-bike. Data will be collected at baseline (T0), immediately post intervention (T1) and at 3-month follow-up (T2). In addition, in the intervention group, data will be collected during the intervention and follow-up periods. Quantitative and qualitative methods will be used. The primary objectives are to determine effective recruitment strategies, establish recruitment and consent rates, adherence and retention in the study, and determine the feasibility and acceptability of the study procedures and intervention. The potential impact of the intervention on clinical, physiological and behavioural outcomes will be assessed to examine intervention promise. Data analyses will be descriptive.DISCUSSION: The findings from these trials will provide information on trial feasibility and highlight the potential of e-cycling as a strategy to positively impact the health and behaviour of individuals with prostate cancer and breast cancer. If appropriate, this information can be used to design and deliver a fully powered definitive trial.TRIAL REGISTRATION: CRANK-B: [ISRCTN39112034]. CRANK-P [ISRCTN42852156]. Registered [08/04/2022] https://www.isrctn.com .</p

The provision of dietary and physical activity advice for men diagnosed with prostate cancer:a qualitative study of the experiences and views of health care professionals, patients and partners

PURPOSE: To explore the views and experiences of health care professionals (HCPs), men diagnosed with localised prostate cancer and their partners about the provision of advice on diet and physical activity after diagnosis and treatment for localised prostate cancer. METHODS: Semi-structured in-depth interviews with ten HCPs (Consultant Urological Surgeons, Uro-Oncology Clinical Nurse Specialists and Allied Health Professionals: see Table 1) and sixteen men diagnosed with localised prostate cancer and seven of their partners. Data from interviews were thematically analysed using the Framework Approach. RESULTS: The men and their partners provided differing accounts to the HCPs and sometimes to each other concerning the provision of advice on diet and physical activity. Some men were unable to recall receiving such advice from HCPs. Factors impacting upon advice-giving included the perceived lack of an evidence base to support dietary and physical activity advice and the credibility of advice providers. The timing of advice provision was a contentious issue as some HCPs believed that patients might not be willing to receive dietary and physical activity advice at the time of diagnosis, whilst others viewed this an opportune time to provide behaviour change information. Patients concurred with the latter opinion. CONCLUSIONS: Men and their partners would value nutritional and physical activity advice from their HCP, after a localised prostate cancer diagnosis. Men would prefer to receive this advice at an early stage in their cancer journey and may implement behaviour change if the received advice is clear and evidence-based. HCPs should receive suitable training regarding what information to provide to men and how best to deliver this information

Adapting Compression Equipment to Accommodate Declining Well Pressures and Ensure Overall Efficiency in Mid/Late Field Life

Case StudyCase Study 9: Compression systems are designed for the governing process conditions. In the Oil and Gas industry, these conditions are often dynamic and a function of reservoir or field characteristics which have varying head and flow rate requirements throughout the field life. The main application objective when designing a gas turbine driven centrifugal compression solution to suit these applications, is to maximize efficiency while minimizing the requirement for additional package modifications or major capital works in mid to late field life. This presentation shows how these objectives were achieved for a case example in South Sumatra, Indonesia where an onshore gas field, feeds a localized gas plant that requires front end compression

Obesity and low levels of physical activity impact on cardiopulmonary fitness in older men after treatment for prostate cancer

The purpose of this study was to compare fitness parameters and cardiovascular disease risk of older and younger men with prostate cancer (PCa) and explore how men's fitness scores compared to normative age values. 83 men were recruited post‐treatment and undertook a cardiopulmonary exercise test (CPET), sit‐to‐stand, step‐and‐grip strength tests and provided blood samples for serum lipids and HbA1c. We calculated waist‐to‐hip ratio, cardiovascular risk (QRISK2), Charlson comorbidity index (CCI) and Godin leisure‐time exercise questionnaire [GLTEQ]. Age‐group comparisons were made using normative data. Men > 75 years, had lower cardiopulmonary fitness, as measured by VO2 Peak (ml/kg/min) 15.8 + 3.8 p 75 years had more cardiovascular risk factors compared to normative standards for men of their age. Although ADT was more frequent in older men, this was not found to be associated with cardiopulmonary fitness, but obesity and low levels of physical activity were. Secondary prevention should be addressed in men with PCa to improve men's overall health

Clinical utility and cost modelling of the phi test to triage referrals into image-based diagnostic services for suspected prostate cancer: the PRIM (Phi to RefIne Mri) study

Abstract: Background: The clinical pathway to detect and diagnose prostate cancer has been revolutionised by the use of multiparametric MRI (mpMRI pre-biopsy). mpMRI however remains a resource-intensive test and is highly operator dependent with variable effectiveness with regard to its negative predictive value. Here we tested the use of the phi assay in standard clinical practice to pre-select men at the highest risk of harbouring significant cancer and hence refine the use of mpMRI and biopsies. Methods: A prospective five-centre study recruited men being investigated through an mpMRI-based prostate cancer diagnostic pathway. Test statistics for PSA, PSA density (PSAd) and phi were assessed for detecting significant cancers using 2 definitions: ≥ Grade Group (GG2) and ≥ Cambridge Prognostic Groups (CPG) 3. Cost modelling and decision curve analysis (DCA) was simultaneously performed. Results: A total of 545 men were recruited and studied with a median age, PSA and phi of 66 years, 8.0 ng/ml and 44 respectively. Overall, ≥ GG2 and ≥ CPG3 cancer detection rates were 64% (349/545), 47% (256/545) and 32% (174/545) respectively. There was no difference across centres for patient demographics or cancer detection rates. The overall area under the curve (AUC) for predicting ≥ GG2 cancers was 0.70 for PSA and 0.82 for phi. AUCs for ≥ CPG3 cancers were 0.81 and 0.87 for PSA and phi respectively. AUC values for phi did not differ between centres suggesting reliability of the test in different diagnostic settings. Pre-referral phi cut-offs between 20 and 30 had NPVs of 0.85–0.90 for ≥ GG2 cancers and 0.94–1.0 for ≥ CPG3 cancers. A strategy of mpMRI in all and biopsy only positive lesions reduced unnecessary biopsies by 35% but missed 9% of ≥ GG2 and 5% of ≥ CPG3 cancers. Using PH ≥ 30 to rule out referrals missed 8% and 5% of ≥ GG2 and ≥ CPG3 cancers (and reduced unnecessary biopsies by 40%). This was achieved however with 25% fewer mpMRI. Pathways incorporating PSAd missed fewer cancers but necessitated more unnecessary biopsies. The phi strategy had the lowest mean costs with DCA demonstrating net clinical benefit over a range of thresholds. Conclusion: phi as a triaging test may be an effective way to reduce mpMRI and biopsies without compromising detection of significant prostate cancers

Acceptability of dietary and physical activity lifestyle modification for men following radiotherapy or radical prostatectomy for localised prostate cancer:a qualitative investigation

Abstract Background The experience and acceptability of lifestyle interventions for men with localised prostate cancer are not well understood, yet lifestyle interventions are increasingly promoted for cancer survivors. We explored the opinions, experiences and perceived acceptability of taking part in nutritional and physical activity interventions amongst men with prostate cancer and their partners; with the ultimate plan to use such information to inform the development of nutritional and physical activity interventions for men with prostate cancer. Methods Semi-structured interviews with 16 men, and seven partners, undergoing curative surgery or radiotherapy for prostate cancer. Interviews explored experiences of lifestyle interventions, acceptable changes participants would make and perceived barriers and facilitators to change. Interviews were thematically analysed using the framework approach. Results Men were frequently open to lifestyle modification and family support was considered vital to facilitate change. Health beneficial, clinician endorsed, understandable, enjoyable interventions were perceived as attractive. Barriers included ‘modern’ digital technology, poor weather, competing commitments or physical limitations, most notably incontinence following radical prostatectomy. Men were keen to participate in research, with few negative aspects identified. Conclusions Men are willing to change behaviour but this needs to be supported by clinicians and health professionals facilitating lifestyle change. An ‘intention-behaviour gap’, when an intended behaviour does not materialise, may exist. Digital technology for data collection and lifestyle measurement may not be suitable for all, and post-surgery urinary incontinence is a barrier to physical activity. These novel findings should be incorporated into lifestyle intervention development, and implemented clinically

Quantitative analysis of ERG expression and its splice isoforms in formalin-fixed, paraffin-embedded prostate cancer samples: Association with seminal vesicle invasion and biochemical recurrence

© American Society for Clinical Pathology. Objectives: The proto-oncogene ETS-related gene (ERG) is consistently overexpressed in prostate cancer. Alternatively spliced isoforms of ERG have variable biological activities; inclusion of exon 11 (72 base pairs [bp]) is associated with aggressiveness and progression of disease. Exon 10 (81 bp) has also been shown to be alternatively spliced. Within this study, we assess whether ERG protein, messenger RNA (mRNA), and ERG splice isoform mRNA expression is altered as prostate cancer progresses. Methods: Detection of the TMPRSS2-ERG fusion was done using direct methods (reverse transcription polymerase chain reaction [PCR] and fluorescence in situ hybridization) and indirect methods for ERG mRNA and protein expression using quantitative PCR and immunohistochemistry, respectively. A linear equation method was used to quantitatively determine relative proportions of ERG variants (ERG72/Δ72, ERG81/Δ81) for each sample. Results: ERG mRNA and protein expression is increased in patients with advanced prostate cancer, with higher levels of ERG expression significantly associated with seminal vesicle invasion (stage pT3b) and biochemical recurrence. Genes involved in cell migration and invasiveness (matrix metalloproteinase 7, osteopontin, and septin 9) are increased in prostate cancers that overexpress ERG. In addition, there is a clear indication of increased retention of exons 10 and 11 in prostate cancer. Conclusions: Analysis of ERG and its variants may be valuable in determining prognosis and development of prostate cancer

NeuroSAFE PROOF randomised controlled feasibility study: brief report of perioperative outcomes, histological concordance, and feasibility

No abstract available

Impact of sex on response to neoadjuvant chemotherapy in patients with bladder cancer

© 2020 Elsevier Ltd. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence http://creativecommons.org/licenses/by-nc-nd/4.0/.Objective: To assess the effect of patient's sex on response to neoadjuvant chemotherapy (NAC) in patients with clinically nonmetastatic muscle-invasive bladder cancer (MIBC). Methods: Complete pathologic response, defined as ypT0N0 at radical cystectomy, and downstaging were evaluated using sex-adjusted univariable and multivariable logistic regression modeling. We used interaction terms to account for age of menopause and smoking status. The association of sex with overall survival and cancer-specific survival was evaluated using Cox regression analyses. Results: A total of 1,031 patients were included in the analysis, 227 (22%) of whom were female. Female patients had a higher rate of extravesical disease extension (P = 0.01). After the administration of NAC, ypT stage was equally distributed between sexes (P = 0.39). On multivariable logistic regression analyses, there was no difference between the sexes or age of menopause with regards to ypT0N0 rates or downstaging (all P > 0.5). On Cox regression analyses, sex was associated with neither overall survival (hazard ratio 1.04, 95% confidence interval 0.75–1.45, P = 0.81) nor cancer-specific survival (hazard ratio 1.06, 95% confidence interval 0.71–1.58, P = 0.77). Conclusion: Our study generates the hypothesis that NAC equalizes the preoperative disparity in pathologic stage between males and females suggesting a possible differential response between sexes. This might be the explanation underlying the comparable survival outcomes between sexes despite females presenting with more advanced tumor stage.Peer reviewedFinal Accepted Versio