Human papillomavirus and the landscape of secondary genetic alterations in oral cancers.

Human papillomavirus (HPV) is a necessary but insufficient cause of a subset of oral squamous cell carcinomas (OSCCs) that is increasing markedly in frequency. To identify contributory, secondary genetic alterations in these cancers, we used comprehensive genomics methods to compare 149 HPV-positive and 335 HPV-negative OSCC tumor/normal pairs. Different behavioral risk factors underlying the two OSCC types were reflected in distinctive genomic mutational signatures. In HPV-positive OSCCs, the signatures of APOBEC cytosine deaminase editing, associated with anti-viral immunity, were strongly linked to overall mutational burden. In contrast, in HPV-negative OSCCs, T>C substitutions in the sequence context 5'-ATN-3' correlated with tobacco exposure. Universal expression of HPV E6*1 and E7 oncogenes was a sine qua non of HPV-positive OSCCs. Significant enrichment of somatic mutations was confirmed or newly identified in PIK3CA, KMT2D, FGFR3, FBXW7, DDX3X, PTEN, TRAF3, RB1, CYLD, RIPK4, ZNF750, EP300, CASZ1, TAF5, RBL1, IFNGR1, and NFKBIA Of these, many affect host pathways already targeted by HPV oncoproteins, including the p53 and pRB pathways, or disrupt host defenses against viral infections, including interferon (IFN) and nuclear factor kappa B signaling. Frequent copy number changes were associated with concordant changes in gene expression. Chr 11q (including CCND1) and 14q (including DICER1 and AKT1) were recurrently lost in HPV-positive OSCCs, in contrast to their gains in HPV-negative OSCCs. High-ranking variant allele fractions implicated ZNF750, PIK3CA, and EP300 mutations as candidate driver events in HPV-positive cancers. We conclude that virus-host interactions cooperatively shape the unique genetic features of these cancers, distinguishing them from their HPV-negative counterparts.

Nomogram predicting the probability of spontaneous stone passage in patients presenting with acute ureteric colic.

OBJECTIVES: To develop a nomogram that could predict spontaneous stone passage (SSP) in patients presenting with acute ureteric colic who are suitable for conservative management. SUBJECT/PATIENTS: A 2517 patient dataset was utilised from an international multi-centre cohort study (MIMIC, A Multi-centre Cohort Study Evaluating the role of Inflammatory Markers In Patients Presenting with Acute Ureteric Colic) of patients presenting with acute ureteric colic across 71 secondary care hospitals in the United Kingdom, Ireland, Australia, and New Zealand. Inclusion criteria mandated a non-contrast CT-KUB. METHODS: SSP was defined as the 'absence of the need for intervention'. The model was developed using logistic regression and backwards selection (to achieve lowest AIC) in a subset from 2009-2015 (n=1728) and temporally validated on a subset from 2016-2017 (n=789). RESULTS: Of the 2517 patients, 1874 had SSP (74.5%). Mean age (±[SD]) was 47 (±14.7) years and 1892 were male (75.2%). At the end of the modelling process, gender: male (OR 0.8, 95%CI 0.64-1.01, p=0.07), neutrophil count (OR 1.03, 95%CI 1.00-1.06, p = 0.08), hydronephrosis (OR 0.79, 95%CI 0.59-1.05, p=0.1), hydroureter (OR 1.3, 95%CI 0.97-1.75, p =0.08), stone size >5-7mm (OR 0.2, 95%CI 0.16-0.25, p<0.0001), stone size >7mm (OR 0.11, 95%CI 0.08-0.15, p<0.001), middle ureter stone position (OR 0.59, 95%CI 0.43-0.81, p=0.001), upper ureter stone position (OR 0.31, 95%CI 0.25-0.39, p<0.001) ), medical expulsive therapy use (OR 1.36, 95%CI 1.1 - 1.67, p = 0.001), oral NSAID use (OR 1.3, 95%CI 0.99 - 1.71, p=0.06), and rectal NSAID use (OR1.17, 95%CI 0.9 - 1.53, p=0.24) remained. Concordance-statistic (C-statistic) was 0.77 (95%CI 0.75 - 0.80) and a nomogram was developed based on these. CONCLUSION: The presented nomogram is available to use as an online calculator via www.BURSTurology.com and could allow clinicians and patients to make a more informed decision on pursuing conservative management versus early intervention.

Independent association of marijuana use and poor oral hygiene with HPV-negative but not HPV-positive head and neck squamous cell carcinomas.

BACKGROUND: Sexual behavior is associated with human papillomavirus (HPV)-positive head and neck cancer, whereas tobacco and alcohol use are associated with HPV-negative cancer. A case-control study was designed to investigate additional demographic and behavioral factors independently associated with these distinct oral cancers. METHODS: From 2011 to 2014, 249 newly diagnosed oral cavity and oropharyngeal squamous cell carcinoma (OSCC) cases were matched (1:2) on age, gender, and self-identified race to 498 controls without a cancer history attending the outpatient otolaryngology clinic at The Ohio State University in Columbus. Cases were stratified by detection of high-risk HPV DNA and RNA in tumors. Demographic and behavioral data were collected using an audio computer-assisted self-interview, and associations with HPV-positive versus HPV-negative OSCCs were investigated by use of univariable and multivariable conditional logistic regression models. RESULTS: After adjustment for oral sexual behavior, the odds of HPV-positive cancer decreased with the patient's years of education. Annual income, tobacco smoking, alcohol drinking, marijuana smoking, and poor oral hygiene were not associated with HPV-positive OSCC. In contrast, the odds of HPV-negative OSCC increased independently with decreased annual income, decreased with a high number of marijuana hit-years, and increased with fewer than annual dental visits after adjustment for lifetime tobacco and alcohol use. Sexual behavior and education were not associated with HPV-negative OSCC. CONCLUSIONS: The distinct risk-factor profiles for HPV-positive and HPV-negative OSCC are confirmed and extended in this case-control study, thus supporting 2 principal etiological pathways for OSCC development. LAY SUMMARY: Sexually acquired human papillomavirus (HPV) infection is an established cause of tonsil and base of tongue cancers. This study compared and contrasted risk factors for HPV-positive and HPV-negative oral cancers. Low number of years of education and sexual behavior are associated with HPV-positive cancer. In contrast, low annual income, infrequent dental visits, and tobacco and alcohol use are associated with HPV-negative cancers. Long-term marijuana use appears protective for HPV-negative cancer. Public health efforts to address these modifiable risk factors may prevent oral cancer.

Development and validation of an individualized risk prediction model for oropharynx cancer in the US population.

BACKGROUND: The incidence of oropharynx cancers has increased substantially in the United States. However, risk stratification tools for the identification of high-risk individuals do not exist. In this study, an individualized risk prediction model was developed and validated for oropharynx cancers in the US population. METHODS: A synthetic, US population-based case-control study was conducted. Oropharynx cancer cases diagnosed at Ohio State University (n = 241) were propensity-weighted to represent oropharynx cancers occurring annually in the United States during 2009-2014 (n = 12,656). Controls (n = 9327) included participants in the National Health and Nutrition Examination Survey (2009-2014) and represented the annual US population aged 30 to 69 years (n = 154,532,508). The individualized 1-year absolute risk of oropharynx cancer was estimated with weighted logistic regression. RESULTS: The risk prediction model included age, sex, race, smoking, alcohol use, lifetime sexual partners, and oral oncogenic human papillomavirus (HPV) status. The model had good discrimination and calibration in split-sample validation (area under the curve [AUC], 0.94; 95% confidence interval [CI], 0.92-0.97; observed/expected [O/E], 1.01; 95% CI, 0.70-1.32) and external validation (AUC, 0.87; 95% CI, 0.84-0.90; O/E, 1.08; 95% CI, 0.77-1.39). In the US population, 1-year predicted risks of oropharynx cancer were highest for older individuals (21.1/100,000 for 65- to 69-year-olds), men (13.9/100,000), whites (10.4/100,000), smokers (18.0/100,000 for >20 pack-years), heavy alcohol users (18.4/100,000), and those with prevalent oral oncogenic HPV (140.4/100,000). The risk prediction model provided substantial risk stratification, with approximately 77% of all oropharynx cancers and approximately 99% of HPV-positive oropharynx cancers occurring in the 10% of the US population with the highest model-predicted risk. CONCLUSIONS: This risk prediction model will enable the efficient design of studies to address the outstanding questions pertaining to the natural history, screening, and secondary prevention of oropharynx cancers.

Factors associated with spontaneous stone passage in a contemporary cohort of patients presenting with acute ureteric colic: results from the Multi-centre cohort study evaluating the role of Inflammatory Markers In patients presenting with acute ureteric Colic (MIMIC) study.

OBJECTIVES: To assess the relationship of white blood cell count (WBC) and other routinely collected inflammatory and clinical markers including stone size, stone position, and medical expulsive therapy use (MET), with spontaneous stone passage (SSP) in a large contemporary cohort of patients with acute ureteric colic, as there are conflicting data on the role of WBC and other inflammatory markers in SSP in patients with acute ureteric colic. PATIENTS AND METHODS: Multicentre retrospective cohort study coordinated by the British Urology Researchers in Surgical Training (BURST) Research Collaborative at 71 secondary care hospitals across four countries (UK, Republic of Ireland, Australia, and New Zealand). In all, 4170 patients presented with acute ureteric colic and a computed tomography confirmed single ureteric stone. Our primary outcome measure was SSP, as defined by the absence of need for intervention to assist stone passage (SP). Multivariable mixed effects logistic regression was used to explore the relationship between key patient factors and SSP. RESULTS: In all, 2518 patients were discharged with conservative management and had further follow-up with a SSP rate of 74% (n = 1874/2518). Sepsis after discharge with conservative management was reported in 0.6% (n = 16/2518). On multivariable analysis neither WBC, neutrophils count, nor C-reactive protein (CRP) predicted SSP, with an adjusted odds ratio (OR) of 0.97 (95% confidence interval [CI] 0.91-1.04, P = 0.38), 1.06 (95% CI 0.99-1.13, P = 0.1) and 1.00 (95% CI 0.99-1.00, P = 0.17), respectively. MET also did not predict SSP (adjusted OR 1.11, 95% CI 0.76-1.61). However, stone size and stone position were significant predictors. SSP for stones <5 mm was 89% (95% CI 87-90) compared to 49% (95% CI 44-53) for stones ≥5-7 mm, and 29% (95% CI 23-36) for stones >7 mm. For stones in the upper ureter the SSP rate was 52% (95% CI 48-56), middle ureter was 70% (95% CI 64-76), and lower ureter was 83% (95% CI 81-85). CONCLUSION: In contrast to the previously published literature, we found that in patients with acute ureteric colic who are discharged with initial conservative management neither WBC, neutrophil count, nor CRP, helps determine the likelihood of SSP. We also found no overall benefit from the use of MET. Stone size and position are important predictors and our present findings represent the most comprehensive SP rates for each millimetre increase in stone size from a large contemporary cohort adjusting for key potential confounders. We anticipate that these data will aid clinicians managing patients with acute ureteric colic and help guide management decisions and the need for intervention.

Elevated urine IL-10 concentrations associate with Escherichia coli persistence in older patients susceptible to recurrent urinary tract infections.

BACKGROUND: Age is a significant risk factor for recurrent urinary tract (rUTI) infections, but the clinical picture is often confused in older patients who also present with asymptomatic bacteriuria (ASB). Yet, how bacteriuria establishes in such patients and the factors underpinning and/or driving symptomatic UTI episodes are still not understood. To explore this further a pilot study was completed in which 30 male and female community based older patients (mean age 75y) presenting clinically with ASB / rUTIs and 15 control volunteers (72y) were recruited and monitored for up to 6 months. During this period symptomatic UTI episodes were recorded and urines collected for urinary cytokine and uropathogenic Escherichia coli (UPEC) analyses. RESULTS: Eighty-six per cent of patients carried E. coli (102 ≥ 105 CFU/ml urine) at some point throughout the study and molecular typing identified 26 different E. coli strains in total. Analyses of urine samples for ten different cytokines identified substantial patient variability. However, when examined longitudinally the pro-inflammatory markers, IL-1 and IL-8, and the anti-inflammatory markers, IL-5 and IL-10, were significantly different in the patient urines compared to those of the controls (P < 0.0001). Furthermore, analysing the cytokine data of the rUTI susceptible cohort in relation to E. coli carriage, showed the mean IL-10 concentration to be significantly elevated (P = 0.04), in patients displaying E. coli numbers ≥105 CFU/ml. CONCLUSIONS: These pilot study data suggest that bacteriuria, characteristic of older rUTI patients, is associated with an immune homeostasis in the urinary tract involving the synthesis and activities of the pro and anti-inflammatory cytokines IL-1, IL-5, IL-8 and IL-10. Data also suggests a role for IL-10 in regulating bacterial persistence.

Significant changes in sexual behavior after a diagnosis of human papillomavirus-positive and human papillomavirus-negative oral cancer.

BACKGROUND: Sexual behavior and oral human papillomavirus (HPV) infection are risk factors for oral squamous cell carcinoma (OSCC). The effects of OSCC diagnosis and treatment on subsequent relationship stress and sexual behavior are unknown. METHODS: Incident cases of HPV-positive or HPV-negative OSCC in patients who had a partnered relationship and partners of patients with oropharyngeal cancer were eligible for a study in which surveys were administered at diagnosis and at the 6-month follow-up time point to assess relationship distress, HPV transmission and concerns about health consequences, and sexual behavior. The frequency distributions of responses, stratified by tumor HPV status, were compared at baseline and follow-up. RESULTS: In total, 262 patients with OSCC and 81 partners were enrolled. Among the patients, 142 (54.2%) had HPV-positive OSCC, and 120 (45.8%) had HPV-negative OSCC. Relationship distress was infrequently reported, and 69% of patients felt that their relationship had strengthened since the cancer diagnosis. Both HPV-positive patients (25%) and their partners (14%) reported feelings of guilt or responsibility for the diagnosis of an HPV-caused cancer. Concern over sexual, but not nonsexual, HPV transmission to partners was reported by 50%. Significant declines in the frequency of vaginal and oral sexual behaviors were reported at follow-up, regardless of tumor HPV status. From baseline to 6 months, significant increases in abstinence from vaginal sex (from 10% to 34%; P < .01) and oral sex (from 25% to 80%; P < .01) were reported. CONCLUSIONS: Diagnosis and treatment of OSCC are associated with significant declines in the frequency of vaginal and oral sex, regardless of tumor HPV status. Sexual behavior is an important quality-of-life outcome to assess within clinical trials. [See related editorial on pages 000-000, this issue.] Cancer 2017. © 2017 American Cancer Society. Cancer 2017;123:1156-1165. © 2016 American Cancer Society.

Medical expulsive therapy in adults with ureteric colic: a multicentre, randomised, placebo-controlled trial.

BACKGROUND: Meta-analyses of previous randomised controlled trials concluded that the smooth muscle relaxant drugs tamsulosin and nifedipine assisted stone passage for people managed expectantly for ureteric colic, but emphasised the need for high-quality trials with wide inclusion criteria. We aimed to fulfil this need by testing effectiveness of these drugs in a standard clinical care setting. METHODS: For this multicentre, randomised, placebo-controlled trial, we recruited adults (aged 18-65 years) undergoing expectant management for a single ureteric stone identified by CT at 24 UK hospitals. Participants were randomly assigned by a remote randomisation system to tamsulosin 400 µg, nifedipine 30 mg, or placebo taken daily for up to 4 weeks, using an algorithm with centre, stone size (≤5 mm or >5 mm), and stone location (upper, mid, or lower ureter) as minimisation covariates. Participants, clinicians, and trial personnel were masked to treatment assignment. The primary outcome was the proportion of participants who did not need further intervention for stone clearance within 4 weeks of randomisation, analysed in a modified intention-to-treat population defined as all eligible patients for whom we had primary outcome data. This trial is registered with the European Clinical Trials Database, EudraCT number 2010-019469-26, and as an International Standard Randomised Controlled Trial, number 69423238. FINDINGS: Between Jan 11, 2011, and Dec 20, 2013, we randomly assigned 1167 participants, 1136 (97%) of whom were included in the primary analysis (17 were excluded because of ineligibility and 14 participants were lost to follow-up). 303 (80%) of 379 participants in the placebo group did not need further intervention by 4 weeks, compared with 307 (81%) of 378 in the tamsulosin group (adjusted risk difference 1·3% [95% CI -5·7 to 8·3]; p=0·73) and 304 (80%) of 379 in the nifedipine group (0·5% [-5·6 to 6·5]; p=0·88). No difference was noted between active treatment and placebo (p=0·78), or between tamsulosin and nifedipine (p=0·77). Serious adverse events were reported in three participants in the nifedipine group (one had right loin pain, diarrhoea, and vomiting; one had malaise, headache, and chest pain; and one had severe chest pain, difficulty breathing, and left arm pain) and in one participant in the placebo group (headache, dizziness, lightheadedness, and chronic abdominal pain). INTERPRETATION: Tamsulosin 400 µg and nifedipine 30 mg are not effective at decreasing the need for further treatment to achieve stone clearance in 4 weeks for patients with expectantly managed ureteric colic. FUNDING: UK National Institute for Health Research Health Technology Assessment Programme.

Individualized volume-corrected maximum flow rate correlates with outcome from bladder outlet surgery in men with lower urinary tract symptoms.

OBJECTIVES: To develop a per-patient volume correction for maximum flow rate using multiple home uroflowmetry, and to carry out a pilot study to determine the most prognostically useful volume at which to evaluate this measurement and estimate its relationship with outcome from disobstructive bladder outlet surgery. METHODS: A total of 30 men carried out home uroflowmetry using a portable device and completed symptom scores before surgery. This was repeated at least 4 months after surgery. For each man's presurgery flow data, voided volume was plotted against maximum flow rate, and a line of best fit with logarithmic form calculated. This allowed maximum flow rate to be corrected for any volume. Percentage reduction in symptom score and increase in mean maximum flow rate were correlated with volume-corrected maximum flow rates. RESULTS: Corrected maximum flow rate at all volumes showed the expected negative correlation with both outcome measures. A statistically significant correlation occurred for volumes >190 mL, with the best performance at volumes >300 mL. CONCLUSIONS: We have devised a novel method allowing estimation of maximum flow rate at any volume, which is a step forward for non-invasive diagnostics. We found this volume-corrected maximum flow rate to correlate significantly with treatment outcome at sufficiently high volumes.

Detrusor after-contraction on ambulatory urodynamics in symptomatic women.

OBJECTIVES: To investigate the association between detrusor after-contraction and urodynamic parameters in a cohort of patients undergoing urodynamic studies by ambulatory monitoring. METHODS: All symptomatic adult female patients with non-neurogenic lower urinary tract dysfunction having ambulatory monitoring over the period January 1998 to January 2014 were included. Urodynamic traces were reviewed to identify detrusor after-contraction. Measured urodynamic variables were Qmax (mL/s), V(void) (mL) and P(det.Qmax) (cmH(2)O). Student's unpaired t-test was used to compare the mean of the variable in the detrusor after-contraction and non-detrusor after-contraction groups. RESULTS: We identified 331 women with a median age of 50 years (range 16-82). Detrusor after-contraction was seen after at least one void in 122 patients giving a prevalence of 37%. A total of 167 (51%) patients had detrusor overactivity. Diagnosis of detrusor overactivity was associated with the presence of detrusor after-contraction (P < 0.05). Overall, patients with detrusor after-contraction had a statistically higher mean P(det.Qmax) (32 vs 28 cmH(2)O, P = 0.04) and lower mean voided volume (300 vs 378 mL, P < 0.001). CONCLUSION: These findings suggest a relatively high prevalence of detrusor after-contraction during ambulatory monitoring, and an association between detrusor overactivity, V(void), P(det.Qmax) and detrusor after-contraction recorded during ambulatory monitoring. Therefore, a link between detrusor after-contractions and the syndrome of overactive bladder can be postulated.

How Men Manage Bulbar Urethral Stricture by Concealing Urinary Symptoms.

In this article, we present findings from research conducted as part of a multi-center surgical trial. Bulbar urethral stricture, a narrowing of the middle urethra, is a common cause of urinary problems in men that can have a profound impact on their lives. Semi-structured interviews were conducted with a sample of 19 men seeking treatment for urethral stricture. The findings reveal how men tend to develop routines and tactics to adapt to their symptoms and hide them from others rather than seek help. We argue that this concealment becomes an inseparable part of how the disease is managed and is an additional hidden practical and emotional burden for these men. In addition, we suggest that the patients only sought curative treatments once practices of social concealment are no longer viable.

High-risk oral human papillomavirus load in the US population, National Health and Nutrition Examination Survey 2009-2010.

We investigated the association of demographic and behavioral factors with oral human papillomavirus (HPV) load for 18 high-risk types among 211 individuals with prevalent high-risk HPV within the National Health and Nutrition Examination Survey 2009-2010. Factors independently associated with HPV load above the median included older age (odds ratio, 1.04 per year increase [95% confidence interval, 1.01-1.07]; P = .004) and intensity of current smoking (P for trend <.001). A marginally greater percentage of men than women had an HPV load above the median (55.7% vs 32.8%; P = .069), and HPV load increased marginally with increasing alcohol use (P for trend = .062). In conclusion, older age and current smoking are associated with a high oral load of high-risk HPV types among individuals with a prevalent infection.

Discontinuation rates and inter-injection interval for repeated intravesical botulinum toxin type A injections for detrusor overactivity.

OBJECTIVE: To report discontinuation rates, inter-injection interval and complication rates after repeated intravesical botulinum toxin type A for the treatment of detrusor overactivity. METHOD: Patients with urodyamically proven detrusor overactivity who had two or more botulinum toxin type A injections in the period 2004-2011 at Freeman Hospital, Newcastle Upon Tyne, UK, were considered for the present study. Discontinuation rates, complication rates and interval between botulinum toxin type A treatments were retrospectively analyzed. RESULTS: Overall, 125 patients (median age 53 years, range 19-83 years) were included in the analysis. The female-to-male ratio was 2.4:1 and median follow up was 38 months. A total of 96 patients had idiopathic detrusor overactivity, whereas 29 had neurogenic detrusor overactivity. A total of 667 injections were carried out, with 125 patients receiving two injections, 60 receiving three injections, 28 receiving four injections, 14 receiving five injections, three receiving six injections, three receiving seven injections and two receiving eight injections. The mean interval (±standard deviation) between the first and second injection (n = 125) was 17.6 months (±10.4), between the second and third (n = 60) was 15.7 ± 7.4 months, between the third and fourth (n = 28) was 15.4 ± 8.6 months, and between the fourth and subsequent injections (n = 22) was 11.6 ± 4.5 months. A total of 26% required intermittent catheterization, and 18% developed recurrent urinary tract infections. There was a discontinuation rate of 25% at 60 months. CONCLUSION: Repeated botulinum toxin type A injections represent a safe and effective method for managing patients with idiopathic detrusor overactivity and neurogenic detrusor overactivity. We have shown that the inter-injection interval remains unchanged up to five injections.

Development and validation of a nomogram predicting recurrence risk in women with symptomatic urinary tract infection.

OBJECTIVES: To develop and externally validate a novel nomogram predicting recurrence risk probability at 12 months in women after an episode of urinary tract infection. METHODS: The study included 768 women from Santa Maria Annunziata Hospital, Florence, Italy, affected by urinary tract infections from January 2005 to December 2009. Another 373 women with the same criteria enrolled at Santa Chiara Hospital, Trento, Italy, from January 2010 to June 2012 were used to externally validate and calibrate the nomogram. Univariate and multivariate Cox regression models tested the relationship between urinary tract infection recurrence risk, and patient clinical and laboratory characteristics. The nomogram was evaluated by calculating concordance probabilities, as well as testing calibration of predicted urinary tract infection recurrence with observed urinary tract infections. Nomogram variables included: number of partners, bowel function, type of pathogens isolated (Gram-positive/negative), hormonal status, number of previous urinary tract infection recurrences and previous treatment of asymptomatic bacteriuria. RESULTS: Of the original development data, 261 out of 768 women presented at least one episode of recurrence of urinary tract infection (33.9%). The nomogram had a concordance index of 0.85. The nomogram predictions were well calibrated. This model showed high discrimination accuracy and favorable calibration characteristics. In the validation group (373 women), the overall c-index was 0.83 (P = 0.003, 95% confidence interval 0.51-0.99), whereas the area under the receiver operating characteristic curve was 0.85 (95% confidence interval 0.79-0.91). CONCLUSIONS: The present nomogram accurately predicts the recurrence risk of urinary tract infection at 12 months, and can assist in identifying women at high risk of symptomatic recurrence that can be suitable candidates for a prophylactic strategy.

Differences in urodynamic voiding variables recorded by conventional cystometry and ambulatory monitoring in symptomatic women.

OBJECTIVES: To determine whether there are differences in pressure and flow measurements between conventional cystometry (CONV) and ambulatory urodynamic monitoring (AMB) in women with overactive bladder syndrome and urinary incontinence. MATERIALS AND METHODS: Retrospective study which included female subjects who underwent both CONV (with saline filling medium) and AMB, separated by less than 24 months, not using medication active on the lower urinary tract and without history of prior pelvic surgery. Both tests were carried out in compliance with the International Continence Society standards. The paired Student's t test was used to compare continuous variables. Bland-Altman statistics were used to assess the agreement of each variable between both studies. RESULTS: Thirty women with a median (range) age of 50 (14 - 73) years met the inclusion criteria. AMB was carried out at a mean (SD) of 11 (6) months after CONV. Measurements of pves and pabd at the end of filling, and Qmax were significantly higher from AMB recordings. There were no differences in pdet at the end of filling, pdetQmax or pdetmax during voiding, nor significant difference in Vvoid. CONCLUSIONS: We provide previously undocumented comparative voiding data between CONV and AMB for patients who most commonly require both investigations. Our findings show higher values of Qmax but similar values of pdetQmax measured by AMB which may partly reflect an overall lower catheter caliber, physiological filling but perhaps also more 'normal' voiding conditions.

Prostate specific antigen enhances the innate defence of prostatic epithelium against Escherichia coli infection.

BACKGROUND: This study investigated whether the increase in serum prostate specific antigen (PSA) typically seen during male urinary tract infection (UTI) is incidental or reflects an innate defence mechanism of the prostate. The protective roles of the whey-acid-motif-4-disulphide core (WFDC) proteins, secretory leukoproteinase inhibitor (SLPI) and WFDC2, in the prostate were also examined. METHODS: UTI recurrence was assessed retrospectively in men following initial UTI by patient interview. PSA, SLPI, and WFDC2 gene expression were assessed using biopsy samples. LNCaP and DU145 in vitro prostate cell models were utilized to assess the effects of an Escherichia coli challenge on PSA and WFDC gene expression, and bacterial invasion of the prostate epithelium. The effects of PSA on WFDC antimicrobial properties were studied using recombinant peptides and time-kill assays. RESULTS: Men presenting with PSA >4 ng/ml at initial UTI were less likely to have recurrent (r) UTI than those with PSA <4 ng/ml [2/15 (13%) vs. 7/10 (70%), P < 0.01]. Genes encoding PSA, SLPI and WFDC2, were expressed in prostatic epithelium, and the PSA and SLPI proteins co-localized in vivo. Challenging LNCaP (PSA-positive) cells with E. coli increased PSA, SLPI, and WFDC2 gene expression (P < 0.05), and PSA synthesis (P < 0.05), and reduced bacterial invasion. Pre-incubation of DU145 (PSA-negative) cells with PSA also decreased bacterial invasion. In vitro incubation of recombinant SLPI and WFDC2 with PSA resulted in peptide proteolysis and increased E. coli killing. CONCLUSIONS: Increased PSA during UTI appears protective against rUTI and in vitro is linked to proteolysis of WFDC proteins supporting enhanced prostate innate defences.

Antimicrobial catheters for reduction of symptomatic urinary tract infection in adults requiring short-term catheterisation in hospital: a multicentre randomised controlled trial.

BACKGROUND: Catheter-associated urinary tract infection (CAUTI) is a major preventable cause of harm for patients in hospital. We aimed to establish whether short-term routine use of antimicrobial catheters reduced risk of CAUTI compared with standard polytetrafluoroethylene (PTFE) catheterisation. METHODS: In our parallel, three group, multicentre, randomised controlled superiority trial, we enrolled adults (aged ≥16 years) requiring short-term (≤14 days) catheterisation at 24 hospitals in the UK. Participants were randomly allocated 1:1:1 with a remote computer allocation to receive a silver alloy-coated catheter, a nitrofural-impregnated catheter, or a PTFE-coated catheter (control group). Patients undergoing unplanned catheterisation were also included and consent for participation was obtained retrospectively. Participants and trial staff were unmasked to treatment assignment. Data were collected by trial staff and by patient-reported questionnaires for 6 weeks after randomisation. The primary outcome was incidence of symptomatic urinary tract infection for which an antibiotic was prescribed by 6 weeks. We postulated that a 3·3% absolute reduction in CAUTI would represent sufficient benefit to recommend routine use of antimicrobial catheters. This study is registered, number ISRCTN75198618. FINDINGS: 708 (10%) of 7102 randomly allocated participants were not catheterised, did not confirm consent, or withdrew, and were not included in the primary analyses. Compared with 271 (12·6%) of 2144 participants in the control group, 263 (12·5%) of 2097 participants allocated a silver alloy catheter had the primary outcome (difference -0·1% [95% CI -2·4 to 2·2]), as did 228 (10·6%) of 2153 participants allocated a nitrofural catheter (-2·1% [-4·2 to 0·1]). Rates of catheter-related discomfort were higher in the nitrofural group than they were in the other groups. INTERPRETATION: Silver alloy-coated catheters were not effective for reduction of incidence of symptomatic CAUTI. The reduction we noted in CAUTI associated with nitrofural-impregnated catheters was less than that regarded as clinically important. Routine use of antimicrobial-impregnated catheters is not supported by this trial. FUNDING: UK National Institute for Health Research Health Technology Assessment Programme.

Relative effectiveness of robot-assisted and standard laparoscopic prostatectomy as alternatives to open radical prostatectomy for treatment of localised prostate cancer: a systematic review and mixed treatment comparison meta-analysis.

OBJECTIVE: To compare the effectiveness of robot-assisted and standard laparoscopic prostatectomy. METHODS: A care pathway was described. We performed a systematic literature review based on a search of Medline, Medline in Process, Embase, Biosis, Science Citation Index, Cochrane Controlled Trials Register, Current Controlled Trials, Clinical Trials, WHO International Clinical Trials Registry and NIH Reporter, the Health Technology Assessment databases, the Database of Abstracts of Reviews of Effects, and relevant conference abstracts up to 31st October 2010). Additionally, reference lists were scanned, an expert panel consulted, and websites of manufacturers, professional organisations, and regulatory bodies were checked. We selected randomised controlled trials (RCTs) and non-randomised comparative studies, published after 1st January 1995, including men with localised prostate cancer undergoing robot-assisted or laparoscopic prostatectomy compared with the other procedure or with open prostatectomy. Studies where at least 90% of included men had clinical tumour stages T1 to T2 and which reported at least one of our specified outcomes were eligible for inclusion. A mixed-treatment comparison meta-analysis was performed to generate comparative statistics on specified outcomes. RESULTS: We included data from 19 064 men across one RCT and 57 non-randomised comparative reports. Robotic prostatectomy had a lower risk of major intra-operative harms such as organ injury [0.4% robotic vs 2.9% laparoscopic], odds ratio ([OR] {95% credible interval [CrI]} 0.16 [0.03 to 0.76]), and a lower rate of surgical margins positive for cancer [17.6% robotic vs 23.6% laparoscopic], OR [95% CrI] 0.69 [0.51 to 0.96]). There was no evidence of a difference in the proportion of men with urinary incontinence at 12 months (OR [95% CrI] 0.55 [0.09 to 2.84]). There were insufficient data on sexual dysfunction. Surgeon learning rates for the procedures did not differ, although data were limited. CONCLUSIONS: Men undergoing robotic prostatectomy appear to have reduced surgical morbidity, and a lower risk of a positive surgical margin, which may reduce rates of cancer recurrence and the need for further treatment, but considerable uncertainty surrounds these results. We found no evidence that men undergoing robotic prostatectomy are disadvantaged in terms of early outcomes. We were unable to determine longer-term relative effectiveness.