Prostate cancer is the most common cancer in men in the United Kingdom. Recent studies suggest that obesity is associated with prostate cancer aggressiveness and higher recurrence rates after treatment. Prognosis may therefore be improved by maintaining healthy weight but research on weight management is relatively scarce. Therefore a weight management programme was designed for prostate cancer patients and a pilot feasibility trial conducted with the aim to evaluate the compliance and effectiveness. Three preliminary studies; a systematic review, a questionnaire survey and qualitative research among patients and their partners, were carried out to inform the optimal design and delivery of the intervention. To identify effective components of the intervention, 778 titles and abstracts were screened in a systematic review. Twenty randomised controlled trials were included in the final review which consisted of six diet interventions, eight exercise interventions and six combined diet and exercise interventions. 256 men completed a mailed questionnaire survey and 48 participants (34 men and 14 partners) participated in six focus group discussions. This mixed-methods research informed the choice of the components, setting and mode of delivery of the intervention. A pilot feasibility study using a two arm randomised controlled trial design compared change in weight and quality of life (QoL) between a 12 week package of a group session, consultant's encouragement letter, monthly individual telephone-based dietitian-led consultations, web-based self-help resources, and pedometer in the intervention group and no intervention in a wait-list control group. 286 men with localized and locally advanced prostate cancer from UCAN (Urology CANcer Charity) Care Centre database were invited to participate of whom 95 responded. Sixty-two eligible men were randomly assigned to intervention (n=31) or wait-list control group (n=31) using minimisation on age, BMI and time since diagnosis. One man in the intervention group and three in the control group withdrew before baseline data collection. Another four men in the intervention group cannot be accommodated into the group schedule. The mean age of the remaining 54 participants at enrolment was 65.5 years (SD 5.6), mean weight 88.9 kg (SD 11.7), BMI 29.6 kgm-2 (SD 2.9) and QoL score 76.6 points (SD 19.0), with no significant difference between the two groups. At 12 weeks, the weight change in the intervention group was greater than in the wait-list control group with a significant group difference of −2.13 kg (95% CI −3.50 to −0.76 kg); p=0.003. The general QoL score change in the intervention group was also greater than in the wait-list control group with a significant group difference of +11.9 points (95% CI 4.6 to 19.2); p=0.002, after adjustment for baseline age, BMI and time since diagnosis. Over weeks 13-24, the intervention group continued to lose weight with a median (IQR) weight change of −1.25 (−3.45, 0.38) kg, which contributed to the overall weight change of −3.40 kg (95% CI −5.27 to −1.53 kg); p=0.001, from week 0-24. The wait-list control was offered a lower-cost mini-intervention of a consultant's encouragement letter, pedometer and the access to the same self-help resources of the weight management programme, but no group meeting or dietetic consultation, from week 13-24. Over this period, the mini-intervention group had a significant weight loss with a weight change of −2.37 kg (95% CI −3.24 to −1.50 kg); p=<0.001. There was no significant change in general QoL or any individual functional or symptom scales in either the intervention or wait-list control group from 12 to 24 weeks. This study can contribute to the future work in this new area which could help to improve clinical outcome in men treated for prostate cancer and inform clinical practice.

Background: Prostate cancer is the most common cancer in Sweden. Due its highly variable behavior, multifocal nature, and insufficient diagnostic methods, prostate cancer is difficult to diagnose and prognosticate. Some patients have an aggressive lethal disease, but the majority of prostate cancer patients have slow-growing, non-lethal disease with long expected survival without treatment. Current diagnostic methods―serum levels of prostate-specific antigen (PSA) and histological grading of biopsied prostate tissue―often do not give the information required to be able to safely differentiate indolent tumors from potentially lethal ones. Many prostate cancers are difficult to detect by imaging, so tissue biopsy cannot be safely guided towards the tumor, and particularly not towards the most aggressive forms. To overcome this problem, multiple needle biopsies are taken from the organ, but biopsies are small and they sample less than 1% of the whole prostate. In this thesis, we explore the non-malignant prostate tissue adjacent to tumors, which is always sampled in biopsies, and we study adaptive changes in this tissue, which may provide new diagnostic and prognostic markers for prostate cancer. We have therefore proposed that this type of tissue should be termed TINT (Tumor Instructed/indicating Normal Tissue).  Methods: In our studies, we used orthotopic rat prostate cancer models with tumors of different aggressiveness. We also used clinical materials from patients diagnosed with prostate cancer at transurethral resection (1975‒1990); the majority of these men were followed with watchful waiting. Analyses were performed with whole-genome expression array, quantitative real-time PCR, immunohistochemistry, and western blotting.  Results: Using the animal model, we found that the presence of a tumor induces changes in gene expression in the surrounding tumor-bearing organ (TINT). The gene signature of TINT was linked to processes such as extracellular matrix organization, immune responses, and inflammation. We also showed that some of these adaptive TINT changes appear to be related to the aggressiveness and metastatic potential of the growing tumor, such as increases in macrophages, in mast cells, in vascular densities, and in vascular cell-proliferation. Some of these findings were confirmed by our observations in patient samples. We found that high staining of the extracellular matrix component hyaluronan in the stroma of the non-malignant prostate tissue was prognostic for short cancer-specific survival. We also found that an elevated proportion of C/EBP-beta positive epithelial cells in non-malignant (TINT) prostate tissue was associated with a good prognosis.  Conclusions: Using animal experiments and patient samples, we showed that the presence of prostate cancer induces changes in the tumor-bearing organ, alterations associated with tumor aggressiveness, and that grading of these changes in TINT can be used to predict outcome in prostate cancer patients.

published_or_final_version / Anatomy / Master / Master of Medical Sciences

No description available.

No description available.

No description available.

No description available.

No description available.

No description available.

No description available.