Health-related quality of life after a diagnosis of bladder cancer: a longitudinal survey over the first year.

OBJECTIVES: To describe the health-related quality of life (HRQoL) of patients in a prospective 12-month observational cohort study of new bladder cancer diagnoses and compare with national cancer and general population surveys. PATIENTS AND METHODS: A prospective UK study in patients with new bladder cancer diagnoses at 13 NHS Trusts. The HRQoL data were collected at 3, 6, 9 and 12 months. Questionnaires used included: the EuroQoL five Dimensions (EQ-5D), European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ)-30-item core, EORTC QLQ-24-item non-muscle-invasive bladder cancer, and EORTC QLQ-30-item muscle-invasive bladder cancer. Results were compared with the Cancer Quality of Life Survey and Health Survey for England. RESULTS: A total of 349 patients were recruited, 296 (85%) completed the first (baseline) and 233 (67%) the final survey. The patients underwent transurethral resection of bladder tumour (TURBT) ± intravesical therapy (238 patients, 80%), radical cystectomy/radiotherapy (51, 17%) or palliation (seven, 2%). At baseline, patients needing radical treatment reported worse HRQoL including lower social function (74.2 vs 83.8, P = 0.002), increased fatigue (31.5 vs 26.1, P = 0.03) and more future worries (39.2 vs 29.4, P = 0.005) than patients who underwent TURBT. Post-treatment surveys showed no change/improvements for patients who underwent TURBT but deterioration for the radically treated cohort. At final survey, reports were similar to baseline, regardless of treatment. Radically treated patients continued to report poorer HRQoL including issues with body image (23.4 vs 12.5, P = 0.007) and male sexual function (75.8 vs 40.4, P < 0.001) compared to those who underwent TURBT. Radically treated patients reported lower EQ-5D utility scores and more problems with usual activities than the general population. DISCUSSION: Patients undergoing TURBT can be reassured regarding HRQoL following treatment. However, those requiring radical treatment report greater changes in HRQoL with the need for appropriate clinical and supportive care to minimise the impact of treatments.

Technical description and outcomes of a continuous anastomosis in open radical prostatectomy.

OBJECTIVE: To describe the surgical technique, objective and subjective medium-term outcomes of a novel continuous vesico-urethral anastomotic suture in open radical prostatectomy (ORP). PATIENTS AND METHODS: A continuous anastomosis comprising separate anterior and posterior monofilament 3-0 polydioxanone sutures, with the bladder neck 'parachuted' down on to the urethral stump, was used in 39 consecutive patients. A cystogram was taken after ORP in the first 23 patients. The catheter was removed as soon as patients were fully mobile. A validated postal questionnaire to determine continence and its effect on quality of life was sent to all patients ≥3 months after ORP. RESULTS: The mean follow-up was 18 months; there were no major complications. There was an insignificant or no leak in 91% of the patients who had a cystogram. Before discharge, 33 patients reported that they were continent, whilst five required a pad(s) for stress incontinence, and one was discharged with a catheter after failing the first catheter removal. Of the 95% who completed the questionnaire, 95% either did not leak urine, or only leaked a small amount; 84% of patients reported that leaking had a minimal effect on everyday life. No patients developed symptomatic urethral or bladder neck stricture/contracture. CONCLUSIONS: Our technique of continuous anastomotic suturing for ORP is safe, reliable and well tolerated. Further randomized studies are warranted to compare the outcome with the standard interrupted vesico-urethral anastomosis.

UScale: a digital device for automatic urine volume measurement and frequency volume charting.

BACKGROUND: Health issues relating to the lower urinary tract are an increasing burden on the health economy. Measurement of urination frequency/volume using diaries to evaluate symptoms and assess severity is established in the management of these health problems. In current practice, these frequency volume diaries are completed by voiding into a measuring jug and the completion of paper or digital charts. Despite being shown useful to diagnosis, this can be a cumbersome method of data collection, leading to issues with patient compliance. In this paper we describe the established benefits of providing clinicians accurate micturition data followed by an analysis of the problems with the current data collection method. METHODS: We introduce our prototype electronic device and accompanying method, which is designed to improve data accuracy and patient compliance, while reducing patient training requirements and clinician workload. RESULTS: The device hardware calibration and testing procedure is described, and two sets of initial data from assumed healthy volunteers are presented, allowing us to demonstrate the advantages of digital data in the fast calculation of diary summary statistics and their potential use to clinicians. CONCLUSIONS: We discuss the design improvements to the UScale device, collection bag, and electronic medical records integration undertaken while validating our described method.

CD40 induces renal cell carcinoma-specific differential regulation of TRAF proteins, ASK1 activation and JNK/p38-mediated, ROS-dependent mitochondrial apoptosis.

A unique feature of CD40 among the TNF receptor (TNFR) superfamily is its exquisitely contextual effects, as originally demonstrated in normal and malignant B-lymphocytes. We studied renal cell carcinoma (RCC) in comparison to normal (human renal proximal tubule) cells, as a model to better understand the role of CD40 in epithelial cells. CD40 ligation by membrane-presented CD40 ligand (mCD40L), but not soluble CD40 agonist, induced extensive apoptosis in RCC cells; by contrast, normal cells were totally refractory to mCD40L. These findings underline the importance of CD40 'signal-quality' on cell fate and explain the lack of pro-apoptotic effects in RCC cells previously, while confirming the tumour specificity of CD40 in epithelial cells. mCD40L differentially regulated TRAF expression, causing sustained TRAF2/TRAF3 induction in RCC cells, yet downregulation of TRAF2 and no TRAF3 induction in normal cells, observations strikingly reminiscent of TRAF modulation in B-lymphocytes. mCD40L triggered reactive oxygen species (ROS) production, critical in apoptosis, and NADPH oxidase (Nox)-subunit p40phox phosphorylation, with Nox blockade abrogating apoptosis thus implying Nox-dependent initial ROS release. mCD40L mediated downregulation of Thioredoxin-1 (Trx-1), ASK1 phosphorylation, and JNK and p38 activation. Although both JNK/p38 were essential in apoptosis, p38 activation was JNK-dependent, which is the first report of such temporally defined JNK-p38 interplay during an apoptotic programme. CD40-killing entrained Bak/Bax induction, controlled by JNK/p38, and caspase-9-dependent mitochondrial apoptosis, accompanied by pro-inflammatory cytokine secretion, the repertoire of which also depended on CD40 signal quality. Previous reports suggested that, despite the ability of soluble CD40 agonist to reduce RCC tumour size in vivo via immunocyte activation, RCC could be targeted more effectively by combining CD40-mediated immune activation with direct tumour CD40 signalling. Since mCD40L represents a potent tumour cell-specific killing signal, our work not only offers insights into CD40's biology in normal and malignant epithelial cells, but also provides an avenue for a 'double-hit' approach for inflammatory, tumour cell-specific CD40-based therapy.

Diagnóstico y manejo actual de la acalasia / Diagnosis and current management of achalasia

Introducción. La acalasia es un trastorno motor del esófago poco común, de etiología no clara, caracterizado por la pérdida de relajación del esfínter esofágico inferior, pérdida del peristaltismo normal, regurgitación y disfagia. Métodos. Se realizó una revisión narrativa de la literatura en revistas científicas y bases de datos en español e inglés, con el fin de presentar información actualizada en lo referente al diagnóstico y tratamiento de esta patología. Resultado. Se presenta la actualización de los criterios de los trastornos motores esofágicos según la clasificación de Chicago (CCv4.0) para el diagnóstico de acalasia y sus subtipos de acuerdo con los nuevos criterios, así como los tratamientos actuales. Conclusión. La acalasia es un trastorno esofágico multimodal, con manifestaciones de predominio gastrointestinal, por lo que su diagnóstico y abordaje terapéutico oportuno es esencial para mejorar la calidad de vida de los pacientes

Introduction. Achalasia is a rare motor disorder of the esophagus of unclear etiology, characterized by loss of lower esophageal sphincter relaxation, loss of normal peristalsis, regurgitation, and dysphagia. Methods. A narrative review of the literature in scientific journals and databases in Spanish and English was carried out, in order to present updated information regarding the diagnosis and treatment of this pathology. Result. The update of the Chicago esophageal motor disorders criteria (CCv4.0) is presented for the diagnosis of achalasia and its subtypes according to the new criteria, as well as current treatments. Conclusion. Achalasia is a multimodal esophageal disorder, with predominantly gastrointestinal manifestations, so its timely diagnosis and therapeutic approach is essential to improve the quality of life of patients.