Development of a disease-specific health-related quality of life (HRQoL) questionnaire intended to be used in conjunction with the general European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) in renal cell carcinoma patients.

BACKGROUND: Studying health-related quality of life (HRQoL) following cancer treatment has become part of a growing number of standardized treatment protocols. The European Organization for Research and Treatment of Cancer (EORTC) has developed HRQoL questionnaires aimed at cancer patients. A disease-specific part is not available for renal cell carcinoma (RCC) patients, and the present aim was to develop an EORTC-compatible RCC-specific HRQoL questionnaire. MATERIAL AND METHODS: In total 413 RCC patients were treated with radical or partial nephrectomies in Western Norway during the period from 1997 to 2010. Three hundred and nine patients with histologically proven cancer were still alive at the inclusion time point and 185 RCC patients (71% response rate) returned the questionnaires. We determined HRQoL by the EORTC-QLQ C30 questionnaire. We also asked 13 candidates questions aimed at constituting a disease-specific part. Furthermore, we tested parts of personality by the Eysenck Personality Inventory and coping by the COPE questionnaire. Given tumor treatment, TNM stage, alcohol consumption level and smoking levels were also determined from the hospital records. RESULTS: A factor analysis showed that five factors were formed: one general symptomatic, one general functional, one with disease-specific questions (flank pain, blood in the urine, flank edema, urinary tract infection), one about sexuality and one about weight loss or gain. Ten RCC-specific HRQoL questions were derived from a factor analysis, including four questions related particularly to pain, mobility and social functioning, also representing a short version of the EORTC C30. The psychometric properties and the relation to other psychological and clinical variables were further determined to be satisfactory. CONCLUSIONS: The suggested disease-specific EORTC-QLQ-style RCC10 version adds important information about the HRQoL of RCC patients, providing additional apparent value to the general questionnaire and personality variables, as well as being psychometrically satisfactory. The questionnaire has a potential as a "stand alone" HRQoL questionnaire among RCC patients.

Pad per day usage, urinary incontinence and urinary tract infections in nursing home residents.

BACKGROUND: many elderly suffer from urinary incontinence and use absorbent pads. Pad use per day (PPD) is a frequently used measure of urinary incontinence. Nursing home residents are often dependent on help from nursing staff to change pads. This study was performed in order to determine whether PPD is a reliable method to quantify urinary incontinence in nursing home residents. Furthermore, the association between urinary tract infections (UTIs), PPD and fluid intake was studied. METHODS: data were retrieved from a multicentre, prospective surveillance among nursing home residents. Data on the use of absorbent pads, fluid intake and incontinence volumes were collected during 48 h. During a 1-year follow-up period, data on UTIs were collected. RESULTS: in this study, 153 residents were included, of whom 118 (77%) used absorbent pads. Residents who used absorbent pads were at increased risk of developing UTIs compared to residents who did not use pads (41 vs 11%; P = 0.001). Daily fluid intake was not associated with UTIs (P = 0.46). The number of pad changes showed no correlation with the risk of developing UTIs (P = 0.62). Patients with a given PPD presented a wide range of incontinence volumes. CONCLUSION: the use of absorbent pads is associated with an increased risk of developing UTIs. PPD and daily fluid intake are not correlated with the risk of developing UTIs. PPD is an unreliable measure of urinary incontinence in nursing home residents.

Dynamic contrast enhanced magnetic resonance imaging of bladder cancer and implications for biological image-adapted radiotherapy.

PURPOSE: To assess the role of image parameters derived from dynamic contrast enhanced magnetic resonance imaging (DCEMRI) in bladder cancer staging, and to investigate the potential use of such parameter images in biological image-adapted radiotherapy (RT). MATERIALS AND METHODS: High-resolution volumetric interpolated breath-hold (VIBE) DCEMRI of 26 patients diagnosed with bladder cancer was performed. DCEMRI parameters derived from tumor and muscle contrast uptake curves were extracted and subjected to correlation analysis with tumor volume as well as clinical, pathological, histological and T2-weighted MR tumor stage. For parameters showing a significant correlation with tumor stage, 3D malignancy maps were generated. As an initial step towards delivery of biologically adapted intensity modulated radiotherapy (IMRT) it was hypothesized that the malignancy map could be used as a RT dose prescription map. Simulating IMRT delivery with multi-leaf collimators (MLCs), idealized dose distributions, constituted by dose cubes, were adapted to the prescription map. The size of the dose cubes were varied to mimic MLCs of varying leaf width. The difference between the adapted and prescribed dose distributions was quantified by the root mean square deviation (RMSD). RESULTS: No significant relationships were found between tumor volume and extracted DCEMRI parameters. The normalized area between tumor and muscle contrast uptake curves (nABC) evaluated from 0-180 seconds (nABC(180)) and 0-480 s (nABC(480)) correlated significantly with tumor stage (p=0.047 and p=0.035, respectively). Dose prescription maps for 10 patients were generated from the nABC(480). The RMSD between the prescribed and adapted dose distribution decreased with decreasing size of the dose cubes. Large interpatient variations in the RMSD and in the dependence of the RMSD on different dose cube sizes were found. CONCLUSIONS: The nABC(180) and nABC(480) may provide added value in staging of bladder cancer. High-resolution IMRT is required for some patients for optimal adapted RT.

A concomitant tumour boost in bladder irradiation: patient suitability and the potential of intensity-modulated radiotherapy.

BACKGROUND AND PURPOSE: In radiotherapy (RT) of bladder cancer, dose escalation without increased adverse effects could be achieved with a concomitant bladder tumour boost. In this study we quantified (1) the fraction of patients suitable for this approach, and (2) the potential of intensity-modulated RT (IMRT) to achieve this boost while also sparing normal tissues. MATERIALS AND METHODS: The fraction of patients suitable for this boost approach was quantified using both a series of 30 radical therapy candidates, and a series of 15 consecutive RT patients. IMRT plans with 3, 5, 7 and 9 equi-spaced beams were set up for the patients in the RT series found suitable for a boost. Two sets of targets were defined, with (i) wide and (ii) narrow margins around both the tumour (prescribed 120% dose) and the non-involved bladder (prescribed 100% dose). The inverse planning optimisation minimised the dose deviation across the targets whilst fulfilling dose-volume histogram (DVH) constraints--based on what could be achieved with conformal RT (CRT)--for both the normal tissues and the targets. RESULTS: Fourteen of the 30 radical therapy candidates (47%) and 10 of the 15 RT patients (67%) were suitable for a boost. The 20% boost could be obtained while maintaining target coverage with at least one IMRT plan in 9 of 10 cases with wide margins and for all 10 cases with narrow margins. Using wide margins, all 3-field plans were unacceptable, the 5-field plans were acceptable for 5 of 10, and the 7- and 9-field plans for 9 of the 10 patients. The normal tissue volumes receiving doses >100% were on average reduced by a factor of 3-4 compared with CRT. The normal tissue volumes receiving intermediate doses (73-88%) decreased slightly, whereas volumes receiving the lowest doses (30-48%) increased with the number of beams. The use of narrow margins resulted in markedly lower normal tissue irradiation. CONCLUSION: This study has shown bladder tumour boosting to be both clinically relevant and technically feasible using IMRT. This approach is ready for clinical implementation, although further improvement could be expected if integrated with target localisation techniques.

Preventing Complications: The Preflight Checklist.

Compliance with the World Health Organisation Surgical Safety Checklist is associated with reduction of complications and mortality.

Gene expression profiles in prostate cancer: association with patient subgroups and tumour differentiation.

Prostate carcinoma is the most common cancer of western men and is a markedly heterogeneous disease. The aim of this study was to identify signatures of differentially expressed genes in prostate cancer using DNA microarray technology, evaluating expression profiles in matched pairs of benign and malignant tissue. Samples were collected from 33 radical prostatectomies, and 52 specimens were included, representing 29 histologically verified primary tumours, 19 paired samples of malignant and benign tissue, and 4 non-paired benign tissue samples. Microarray analysis was performed using an expanded sequence verified set of 40,000 human cDNA clones, revealing several genes with significant differences between malignant and benign tissue, including recently reported genes like alpha-methylacyl-CoA racemase (AMACR) and hepsin, as well as genes relevant for tumour development and progression. Leave out cross validation (LOCV) test correctly predicted tumour or benign tissue in 47 (90.3%) out of 52 cases, significantly better than cross validation tests using randomly permuted tissue labels. Unsupervised clustering analysis revealed 3 distinct patient clusters significantly associated with Gleason score, and high grade tumours (Gleason score >/=7) accumulated in cluster 1 (C1). Gene expression profiles correctly predicted 100% of tumour samples segregating to C1, as also validated by LOCV. Gene expression profiles were analysed in filtered and floored datasets with similar results, and a pair-wise design was also tested. Gene expression profiles provided tumour clusters linked to differentiation, and revealed novel markers relevant for molecular classification, grading and therapy of prostate cancer.

Health-related quality of life, personality and choice of coping are related in renal cell carcinoma patients.

OBJECTIVE: To investigate whether health-related quality of life (HRQoL) depends on psychosocial factors, rather than on factors related to the cancer treatment, this study explored the associations between HRQoL, personality, choice of coping and clinical parameters in surgically treated renal cell carcinoma (RCC) patients. MATERIALS AND METHODS: After exclusions (e.g. death, dementia), 260 patients were found to be eligible and invited to participate. The response rate was 71%. HRQoL was determined by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), personality by the Eysenck Personality Inventory and coping by the COPE Questionnaire. Given tumour treatment, TNM stage and patient-reported comorbidity were also determined. The HRQoL indices were also summarized in general quality of life/health, functional sum and symptom sum scores. RESULTS: EORTC C30 sum scores were negatively associated with the personality trait of neuroticism [common variance (CV) 19-36%]. Avoidant choice of coping inversely accounted for 9-18% of the total HRQoL variance, while reported coping by humour was to some extent negatively associated with HRQoL score (CVmax 4%). Indeed, all of the quality of life indices except for one were significantly negatively correlated with neuroticism and avoidance coping. Patients with low HRQoL due to treatment, secondary to flank or open surgery, reported a closer association between problem-focused choice of coping and HRQoL than the other patients. Moreover, present comorbidities were uniquely associated with a lowered HRQoL. CONCLUSIONS: HRQoL is related to treatment-related factors in RCC patients, but shown here to be more strongly associated with psychological factors and present comorbidity. These findings suggest that attention should be paid to supportive treatment of RCC patients.

Prophylactic breast irradiation with a single dose of electron beam radiotherapy (10 Gy) significantly reduces the incidence of bicalutamide-induced gynecomastia.

PURPOSE: To evaluate the efficacy and tolerability of prophylactic breast irradiation in reducing the incidence and severity of bicalutamide-induced gynecomastia and breast pain. METHODS AND MATERIALS: In all, 106 men with prostate cancer (T1b-T4/Nx/M0) and no current gynecomastia/breast pain were enrolled in this randomized, sham-controlled, double-blind, parallel-group multicenter trial. Patients received either a single dose of electron beam radiotherapy (10 Gy) or sham radiotherapy. Bicalutamide (Casodex) 150 mg/day was administered for 12 months from the day of radiotherapy. Every 3 months, patients underwent physical examination and questioning about gynecomastia and breast pain. RESULTS: The incidence of investigator-assessed gynecomastia was significantly lower with radiotherapy vs. sham radiotherapy (52% vs. 85%; odds ratio [OR], 0.13; 95% confidence interval [CI], 0.04, 0.38; p < 0.001); direct questioning showed similar results. Fewer radiotherapy patients had >/=5 cm gynecomastia (measured by calipers; 11.5% vs. 50.0% for sham radiotherapy), and fewer cases were moderate-to-severe in intensity (21% vs. 48%). Similar proportions of radiotherapy and sham radiotherapy patients experienced breast pain (83% vs. 91%; OR, 0.25; 95% CI, 0.05, 1.27; p = 0.221); patients receiving radiotherapy experienced some reduction in its severity (OR, 0.44; 95% CI, 0.20, 0.97; p = 0.0429). CONCLUSIONS: Prophylactic breast irradiation is an effective and well-tolerated strategy for prevention of bicalutamide-induced gynecomastia.

Clinical value of uroflowmentry in selected cases of bladder outlet obstruction.

Fifteen patients with Benign Prostatic Hyperplasia (BPH), 42 urethral stricture patients, and 34 controls were included in this study to describe outflowmetry findings at Tikur Anbessa Hospital in Addis Abeba from April to August 2000. Normal values for maximum and average urine flow rates were determined Uroflowmetry findings in BPH and urethral stricture were compared with normal subjects. The average age for BPH, urethral stricture, and controls were 63.3 (SD +/- 10.3), 38.4 (SD +/- 12.4), and 28.5 (SD +/- 7.9) respectively. The mean maximum flow rates for normal subjects was 22.7 ml/sec (range 15 to 42 ml/sec) and mean average flow rates 14.7 ml/sec (range 9 to 25 ml/sec). Mean maximum flow rate for BPH and Urethral Stricture were 11.5 (SD +/- 8.2) and 8.7 (SD +/- 6.5) ml/sec respectively. For urethral stricture maximum flow rate had sensitivity and specificity of 91% and 85% respectively. For BPH sensitivity was 100% and specificity 80%. Normal values are set for the study population. Uroflowmetry has high sensitivity and specificity. It can widely be used in routine-evaluation of BPH and urethral stricture patients.

International prostate symptom score as a clinical outcome measure for Ethiopian patients with urethral stricture.

Eighty-four urethral stricture patients and 73 controls were studied prospectively over a 6 months period in Tikur Anbessa Hospital from April to August 2000. The purpose of the study was to evaluate the use of International Prostate Symptom Score (IPSS) as an outcome measurement instrument for urethral stricture patients in Ethiopia. The Amharic translation of IPSS (IPSS Amh) was used in this study. Internal consistency was 0.91. Construct validity was 0.73. Test-retest reliability was 0.95. Sensitivity and specificity were 76% and 71% respectively. In conclusion the IPSS Amh was found to be valid for use in urethral stricture patients in Ethiopia. We recommend the wide use of this cheap and easily available clinical measurement instrument.

Residual urine as a risk factor for lower urinary tract infection: a 1-year follow-up study in nursing homes.

OBJECTIVES: To determine whether postvoid urine is a risk factor for the development of lower urinary tract infections (UTIs) in nursing home residents. DESIGN: Prospective surveillance with a follow-up period of 1 year. SETTING: Six Norwegian nursing homes. PARTICIPANTS: One hundred fifty nursing home residents. METHODS: Postvoid residual (PVR) urine volumes were measured using a portable ultrasound. UTIs were registered prospectively for 1 year. RESULTS: Ninety-eight residents (65.3%) had a PVR less than 100 mL, and 52 (34.7%) had a PVR of 100 mL or greater. During the follow-up period, 51 residents (34.0%) developed one or more UTIs. The prevalence of UTI in women was higher than in men (40.4% vs 19.6%; P=.02). There was no significant difference in mean PVR between residents who did and did not develop a UTI (79 vs 97 mL, P=.26). PVR of 100 mL or greater was not associated with greater risk of developing a UTI (P=.59). CONCLUSION: High PVR is common in nursing home residents. No association between PVR and UTI was found.

Renal cell carcinoma: a clinicopathological follow-up study after radical nephrectomy.

OBJECTIVE: To examine the prognostic significance of performance status, tumour stage, histological subtype, nuclear grade and histological tumour necrosis (HTN) in a population of consecutive patients subjected to radical nephrectomy for renal cell carcinoma (RCC). MATERIAL AND METHODS: The cohort consisted of 110 males and 86 females with a mean age of 66 years (range 39-88 years). The Eastern Cooperative Oncology Group performance status (ECOG PS) was determined in all cases. The tumours were staged according to the 2002 TNM classification of the American Joint Committee on Cancer. Histological subtype was diagnosed using the Heidelberg classification. Nuclear grading was performed by means of Fuhrman's method. The median follow-up period was 65 months (mean 83 months; range 1-232 months). RESULTS: Median overall survival (OS) was 65 months and median cancer-specific survival (CSS) was 171 months. CSS was correlated with TNM classification, with the longest survival occurring for stage I and II tumours, shorter survival for stage III tumours and shortest survival for stage IV tumours (p<0.001). A significant difference in CSS was found between T1N0M0 and T2N0M0 tumours (p<0.01). A 15-year CSS of 100% was revealed in patients with tumours

Multiple primary malignancies in patients with renal cell carcinoma: a national population-based cohort study.

OBJECTIVE: To determine the possibly greater occurrence of multiple malignancies in patients with renal cell carcinoma (RCC). PATIENTS AND METHODS: In the 7-year period 1987-93, all 1425 patients aged 15-70 years with registered histopathologically verified RCC in Norway were included in the study. All clinical and histopathology reports were checked manually, to verify the registered diagnosis and to ensure that no tumour was a metastasis from another. After this process, 257 patients (287 tumours other than RCC) with multiple primary malignancies were identified. The primary tumours other than RCC were classified as antecedent, synchronous and subsequent. For the subsequently occurring tumours, the expected number of different tumour types was calculated according to age group, gender and observation time. RESULTS: Of the 1425 patients, 228 (16%) had one, 23 (1.6%) had two, three (0.2%) had three and one (0.07%) had four other primary malignancies. In all, 100 (34.8%) of the other tumours were diagnosed as antecedent, 53 (18.7%) as synchronous and 134 (46.7%) as subsequent to the RCC. Cancer in the prostate, bladder, lung, breast, colon and rectal cancer, malignant melanomas (MM) and non-Hodgkin's lymphomas (NHL) were the most common other malignancies. The observed overall number of subsequent other malignant tumours was 22% higher than the expected number. The observed number of subsequent tumours was significantly higher for bladder cancer, NHL and MM. The estimated 15-year cumulative risk for patients with RCC and no previous or synchronous other malignancy for developing a later second cancer was 26.6% in men, and 15.5% in women (statistically significant, P = 0.04). Patients with antecedent or synchronous other cancer had significantly poorer overall survival than those without. CONCLUSIONS: Patients with RCC seem to have a significantly higher risk of developing other subsequent primary malignancies. This should be considered during the follow-up of patients with RCC.

Radiation dose escalation combined with hormone therapy improves outcome in localised prostate cancer.

We present the impact of systematic radiation dose escalation from 64 Gy to 66 Gy to 70 Gy on the outcome after radiation therapy (RT) alone or combined with hormonal treatment (HT) in a series of 494 consecutive localised prostate cancer patients treated during 1990-1999. Prognostic factors for prostate-specific antigen (PSA) failure, overall survival (OS) and prostate cancer specific survival (CSS) were investigated using multivariate analysis. T stage, pre-treatment PSA, grade, radiation dose and HT were found to be independent predictors of PSA failure. T stage, grade and HT were also independent predictors of both OS and CSS, while radiation dose was a significant predictor for OS and indicated a trend (p = 0.07) for CSS. A dose of 70 Gy combined with hormonal treatment improves PSA failure free survival and survival in localised prostate cancer compared with doses of 64-66 Gy.

The potentially curable prostate cancer patient and the pathways leading to diagnosis and treatment.

OBJECTIVE: Potentially curable prostate cancer is a diagnostic challenge for the general practitioner (GP). In a defined catchment area we wanted to discover why patients consulted their GPs and the reasons for their referral to the urologist. MATERIAL AND METHODS: Patients remitted to our "early prostate cancer clinic" with suspected potentially curable prostate cancer between January 1997 and December 2000 were included in the study. Patient information was registered according to a prospectively designed protocol. RESULTS: Of the 872 patients examined, prostate cancer was diagnosed in 41.3% (360/872). Median age was 63.1 years and median total prostate-specific antigen (PSA) level was 8.6 microg/l. The main reason for referral to a urologist was elevated PSA alone. However, the majority of the patients had no urological symptoms when they consulted their GP. As no local or national screening recommendations existed, we believe that opportunistic PSA screening has been common. CONCLUSIONS: The most important reason for referring patients to our specialist clinic was elevated PSA, often detected by means of opportunistic PSA screening. This study shows the effect of PSA testing in real-life practice.

Tamsulosin: efficacy and safety in patients with neurogenic lower urinary tract dysfunction due to suprasacral spinal cord injury.

PURPOSE: We evaluated the efficacy and safety of tamsulosin in patients with neurogenic lower urinary tract dysfunction secondary to suprasacral spinal cord lesions in a 4-week randomized controlled trial (RCT) followed by a 1-year, open label, long-term study. MATERIALS AND METHODS: A total of 263 patients were randomized to 4-week double-blind therapy with placebo, or 0.4 or 0.8 mg tamsulosin once daily. Of these, 244 patients completed the RCT, 186 continued long-term tamsulosin therapy (0.4 or 0.8 mg once daily) and 134 completed 1-year treatment. The primary efficacy parameter was maximum urethral pressure (MUP). RESULTS: Although the mean decrease in MUP at 4 weeks in the RCT did not reach statistical significance over the placebo, it was more pronounced with 0.4 (-12.2 cm H2O or -10%) and 0.8 mg (-9.6 cm H2O or -9%) tamsulosin than placebo (-6.5 cm H2O or -3%). In the long-term study there was a statistically significant mean decrease in MUP (-18.0 cm H2O, p <0.001 or -15%) from baseline to end point. In the long-term study tamsulosin also decreased maximum urethral closure pressure, improved several cystometry parameters related to bladder storage and emptying, and increased to a statistically significantly degree, from baseline to end point, mean voided volume based on the micturition diary. There was statistically significant improvement for the International Prostate Symptom Score Quality of Life, as well as several questions about symptoms related to urinary leakage, and 1 question on bladder emptying and frequency, bother and severity of symptoms of autonomic dysreflexia. Finally, 71% of patients improved according to investigators (44% slightly and 27% much improved). Both doses were effective and well tolerated. CONCLUSIONS: Long-term tamsulosin treatment (0.4 and 0.8 mg once daily) seems to be effective and well tolerated in patients with neurogenic lower urinary tract dysfunction. The results suggest that it improves bladder storage and emptying, and decreases symptoms of autonomic dysreflexia.