The optimal healthy ranges of thyroid function defined by the risk of cardiovascular disease and mortality: systematic review and individual participant data meta-analysis.

BACKGROUND: Reference intervals of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) are statistically defined by the 2·5-97·5th percentiles, without accounting for potential risk of clinical outcomes. We aimed to define the optimal healthy ranges of TSH and FT4 based on the risk of cardiovascular disease and mortality. METHODS: This systematic review and individual participant data (IPD) meta-analysis identified eligible prospective cohorts through the Thyroid Studies Collaboration, supplemented with a systematic search via Embase, MEDLINE (Ovid), Web of science, the Cochrane Central Register of Controlled Trials, and Google Scholar from Jan 1, 2011, to Feb 12, 2017 with an updated search to Oct 13, 2022 (cohorts found in the second search were not included in the IPD). We included cohorts that collected TSH or FT4, and cardiovascular outcomes or mortality for adults (aged ≥18 years). We excluded cohorts that included solely pregnant women, individuals with overt thyroid diseases, and individuals with cardiovascular disease. We contacted the study investigators of eligible cohorts to provide IPD on demographics, TSH, FT4, thyroid peroxidase antibodies, history of cardiovascular disease and risk factors, medication use, cardiovascular disease events, cardiovascular disease mortality, and all-cause mortality. The primary outcome was a composite outcome including cardiovascular disease events (coronary heart disease, stroke, and heart failure) and all-cause mortality. Secondary outcomes were the separate assessment of cardiovascular disease events, all-cause mortality, and cardiovascular disease mortality. We performed one-step (cohort-stratified Cox models) and two-step (random-effects models) meta-analyses adjusting for age, sex, smoking, systolic blood pressure, diabetes, and total cholesterol. The study was registered with PROSPERO, CRD42017057576. FINDINGS: We identified 3935 studies, of which 53 cohorts fulfilled the inclusion criteria and 26 cohorts agreed to participate. We included IPD on 134 346 participants with a median age of 59 years (range 18-106) at baseline. There was a J-shaped association of FT4 with the composite outcome and secondary outcomes, with the 20th (median 13·5 pmol/L [IQR 11·2-13·9]) to 40th percentiles (median 14·8 pmol/L [12·3-15·0]) conveying the lowest risk. Compared with the 20-40th percentiles, the age-adjusted and sex-adjusted hazard ratio (HR) for FT4 in the 80-100th percentiles was 1·20 (95% CI 1·11-1·31) for the composite outcome, 1·34 (1·20-1·49) for all-cause mortality, 1·57 (1·31-1·89) for cardiovascular disease mortality, and 1·22 (1·11-1·33) for cardiovascular disease events. In individuals aged 70 years and older, the 10-year absolute risk of composite outcome increased over 5% for women with FT4 greater than the 85th percentile (median 17·6 pmol/L [IQR 15·0-18·3]), and men with FT4 greater than the 75th percentile (16·7 pmol/L [14·0-17·4]). Non-linear associations were identified for TSH, with the 60th (median 1·90 mIU/L [IQR 1·68-2·25]) to 80th percentiles (2·90 mIU/L [2·41-3·32]) associated with the lowest risk of cardiovascular disease and mortality. Compared with the 60-80th percentiles, the age-adjusted and sex-adjusted HR of TSH in the 0-20th percentiles was 1·07 (95% CI 1·02-1·12) for the composite outcome, 1·09 (1·05-1·14) for all-cause mortality, and 1·07 (0·99-1·16) for cardiovascular disease mortality. INTERPRETATION: There was a J-shaped association of FT4 with cardiovascular disease and mortality. Low concentrations of TSH were associated with a higher risk of all-cause mortality and cardiovascular disease mortality. The 20-40th percentiles of FT4 and the 60-80th percentiles of TSH could represent the optimal healthy ranges of thyroid function based on the risk of cardiovascular disease and mortality, with more than 5% increase of 10-year composite risk identified for FT4 greater than the 85th percentile in women and men older than 70 years. We propose a feasible approach to establish the optimal healthy ranges of thyroid function, allowing for better identification of individuals with a higher risk of thyroid-related outcomes. FUNDING: None.

Description of the EuroTARGET cohort: A European collaborative project on TArgeted therapy in renal cell cancer-GEnetic- and tumor-related biomarkers for response and toxicity.

OBJECTIVE: For patients with metastatic renal cell cancer (mRCC), treatment choice is mainly based on clinical parameters. With many treatments available and the limited response to treatment and associated toxicities, there is much interest in identifying better biomarkers for personalized treatment. EuroTARGET aims to identify and characterize host- and tumor-related biomarkers for prediction of response to tyrosine kinase inhibitor therapy in mRCC. Here, we describe the EuroTARGET mRCC patient cohort. METHODS AND MATERIALS: EuroTARGET is a European collaborative project designed as an observational study for which patients with mRCC were recruited prospectively in 62 centers. In addition, 462 patients with mRCC from previous studies were included. Detailed clinical information (baseline and follow-up) from all patients was entered in web-based case record forms. Blood was collected for germline DNA and pharmacokinetic/pharmacodynamic analyses and, where available, fresh-frozen tumor material was collected to perform tumor DNA, RNA, kinome, and methylome analyses. RESULTS: In total, 1,210 patients with mRCC were included. Of these, 920 received a tyrosine kinase inhibitor as first-line targeted treatment (sunitinib [N = 713, 78%], sorafenib [N = 41, 4%], or pazopanib [N = 166, 18%]) and had at least 6 months of outcome assessment (median follow-up 15.3 months [interquartile range: 8.5-30.2 months]). Germline DNA samples were available from 824 of these patients, fresh-frozen tumor material from 142 patients, fresh-frozen normal kidney tissue from 95 patients, and tissue microarrays created from formalin-fixed paraffin-embedded tumor material from 247 patients. Of the 920 patients, germline DNA variant chip data were successfully generated for 811 patients (Illumina HumanOmniExpress BeadChip). For 80 patients, next-generation exome sequencing of germline and tumor DNA was performed, tumor RNA sequencing was performed for 124 patients, kinome activity measured and processed for 121 patients (PamChip), and methylome data (Illumina Infinium HumanMethylation450 BeadChip) were created for 116 RCC tissues (and 23 normal kidney tissues). For 73 out of the 920 patients, all platform data types were generated. In addition, 40 patients were included in a pharmacokinetic/pharmacodynamic phase IV substudy. CONCLUSIONS: Analysis of EuroTARGET cohort data will contribute to personalization of therapy for patients with mRCC. The extensive clinical data and multiplatform EuroTARGET data will be freely available.

A short-term intervention with selenium affects expression of genes implicated in the epithelial-to-mesenchymal transition in the prostate.

In parallel with the inconsistency in observational studies and chemoprevention trials, the mechanisms by which selenium affects prostate cancer risk have not been elucidated. We conducted a randomized, placebo-controlled trial to examine the effects of a short-term intervention with selenium on gene expression in non-malignant prostate tissue. Twenty-three men received 300 µg selenium per day in the form of selenized yeast (n=12) or a placebo (n=11) during 5 weeks. Prostate biopsies collected from the transition zone before and after intervention were analysed for 15 participants (n=8 selenium, n=7 placebo). Pathway analyses revealed that the intervention with selenium was associated with down-regulated expression of genes involved in cellular migration, invasion, remodeling and immune responses. Specifically, expression of well-established epithelial markers, such as E-cadherin and epithelial cell adhesion molecule EPCAM, was up-regulated, while the mesenchymal markers vimentin and fibronectin were down-regulated after intervention with selenium. This implies an inhibitory effect of selenium on the epithelial-to-mesenchymal transition (EMT). Moreover, selenium was associated with down-regulated expression of genes involved in wound healing and inflammation; processes which are both related to EMT. In conclusion, our explorative data showed that selenium affected expression of genes implicated in EMT in the transition zone of the prostate.

Consortium analysis of gene and gene-folate interactions in purine and pyrimidine metabolism pathways with ovarian carcinoma risk.

SCOPE: We reevaluated previously reported associations between variants in pathways of one-carbon (1-C) (folate) transfer genes and ovarian carcinoma (OC) risk, and in related pathways of purine and pyrimidine metabolism, and assessed interactions with folate intake. METHODS AND RESULTS: Odds ratios (OR) for 446 genetic variants were estimated among 13,410 OC cases and 22,635 controls, and among 2281 cases and 3444 controls with folate information. Following multiple testing correction, the most significant main effect associations were for dihydropyrimidine dehydrogenase (DPYD) variants rs11587873 (OR = 0.92; p = 6 × 10⁻5) and rs828054 (OR = 1.06; p = 1 × 10⁻4). Thirteen variants in the pyrimidine metabolism genes, DPYD, DPYS, PPAT, and TYMS, also interacted significantly with folate in a multivariant analysis (corrected p = 9.9 × 10⁻6) but collectively explained only 0.2% of OC risk. Although no other associations were significant after multiple testing correction, variants in SHMT1 in 1-C transfer, previously reported with OC, suggested lower risk at higher folate (p(interaction) = 0.03-0.006). CONCLUSION: Variation in pyrimidine metabolism genes, particularly DPYD, which was previously reported to be associated with OC, may influence risk; however, stratification by folate intake is unlikely to modify disease risk appreciably in these women. SHMT1 SNP-by-folate interactions are plausible but require further validation. Polymorphisms in selected genes in purine metabolism were not associated with OC.

Cancer incidence in Dutch Balkan veterans.

Suspicion has been raised about an increased cancer risk among Balkan veterans because of alleged exposure to depleted uranium. The authors conducted a historical cohort study to examine cancer incidence among Dutch Balkan veterans. Male military personnel (n=18,175, median follow-up 11 years) of the Army and Military Police who had been deployed to the Balkan region (1993-2001) was compared with their peers not deployed to the Balkans (n=135,355, median follow-up 15 years) and with the general Dutch population of comparable age and sex. The incidence of all cancers and 4 main cancer subgroups was studied in the period 1993-2008. The cancer incidence rate among Balkan deployed military men was 17% lower than among non-Balkan deployed military men (hazard ratio 0.83 (95% confidence interval 0.69, 1.00)). For the 4 main cancer subgroups, hazard ratios were statistically non-significantly below 1. Also compared to the general population cancer rates were lower in Balkan deployed personnel (standardised incidence rate ratio (SIR) 0.85 (0.73, 0.99). The SIR for leukaemia was 0.63 (0.20, 1.46). The authors conclude that earlier suggestions of increased cancer risks among veterans are not supported by empirical data. The lower risk of cancer might be explained by the 'healthy warrior effect'.

Discrepancy between clinical staging through bimanual palpation and pathological staging after cystectomy.

OBJECTIVES: In muscle invasive bladder cancer (MIBC), careful clinical staging is essential for patient counseling and decision-making. Bimanual palpation (BP) is an integral part and guideline advice of clinical staging. Until now, however, the value of BP has never been studied. With this study, we aim to determine the accuracy of clinical staging through BP. METHODS: Detailed clinical data were collected from a population-based series of 1,409 patients with MIBC, diagnosed between 1989 and 2005, in the region of the Comprehensive Cancer Centre East in The Netherlands. Selected were all patients who underwent BP (n = 738). Preoperative tumor-stage (cT-stage) determined through BP was compared with post-cystectomy pT-stage. Contingency tables were made to determine the correlation between cT-stage and pT-stage. RESULTS: In 18 of 142 patients in whom BP showed an organ-confined tumor, the tumor was unresectable (pT4) at the time of surgery. Four out of 9 patients who had a suspected T4 tumor on BP but who underwent cystectomy anyway appeared to have operable tumors at cystectomy. In 87 patients (57.6%), accurate staging through BP was observed. In 17 patients (11.3%), clinical overstaging was found, and in 47 patients, (31.1%) clinical understaging. CONCLUSIONS: Frequently, pT-stage after cystectomy does not correlate with preoperative cT-stage based on BP. Discrepancy was observed in 42% of the patients: in 11%, clinical overstaging and in 31%, clinical understaging. Based on these data, some caution is suggested when interpreting the outcome of BP. Prospective data is needed for a more formal evaluation of the staging accuracy of BP.

Sequence variants at CYP1A1-CYP1A2 and AHR associate with coffee consumption.

Coffee is the most commonly used stimulant and caffeine is its main psychoactive ingredient. The heritability of coffee consumption has been estimated at around 50%. We performed a meta-analysis of four genome-wide association studies of coffee consumption among coffee drinkers from Iceland (n = 2680), The Netherlands (n = 2791), the Sorbs Slavonic population isolate in Germany (n = 771) and the USA (n = 369) using both directly genotyped and imputed single nucleotide polymorphisms (SNPs) (2.5 million SNPs). SNPs at the two most significant loci were also genotyped in a sample set from Iceland (n = 2430) and a Danish sample set consisting of pregnant women (n = 1620). Combining all data, two sequence variants significantly associated with increased coffee consumption: rs2472297-T located between CYP1A1 and CYP1A2 at 15q24 (P = 5.4 · 10(-14)) and rs6968865-T near aryl hydrocarbon receptor (AHR) at 7p21 (P = 2.3 · 10(-11)). An effect of ∼0.2 cups a day per allele was observed for both SNPs. CYP1A2 is the main caffeine metabolizing enzyme and is also involved in drug metabolism. AHR detects xenobiotics, such as polycyclic aryl hydrocarbons found in roasted coffee, and induces transcription of CYP1A1 and CYP1A2. The association of these SNPs with coffee consumption was present in both smokers and non-smokers.

Body mass index is not a predictor of biochemical recurrence after radical prostatectomy in Dutch men diagnosed with prostate cancer.

PURPOSE: To determine the effect of body mass index (BMI) on clinical and pathological characteristics at time of diagnosis and on risk of biochemical recurrence after radical prostatectomy among Dutch men diagnosed with prostate cancer. METHODS: In total, 1,116 prostate cancer patients with known BMI, diagnosed between 2003 and 2006, were identified from the population-based cancer registry held by the Comprehensive Cancer Centre East, The Netherlands. Of these, 504 patients underwent a radical prostatectomy. Patients were categorized as normal weight (BMI < 25 kg/m(2)), overweight (BMI 25-30 kg/m(2)), or obese (BMI ≥ 30 kg/m(2)). Multivariable proportional hazards regression models, adjusted for age, prediagnostic PSA levels, and pathological characteristics were used to evaluate BMI as a prognostic factor for biochemical recurrence after radical prostatectomy. RESULTS: Overall, clinical and biopsy characteristics did not significantly differ among BMI groups. Pathological characteristics after radical prostatectomy did not significantly differ among BMI groups, except for tumor stage, which was highest in obese patients (P = 0.017). For patients treated with radical prostatectomy, 5-year risk (95% Confidence Intervals) of biochemical recurrence was 30% (23-37%) for normal weight, 32% (25-39%) for overweight, and 25% (9-41%) for obese patients (log rank P = 0.810). BMI was not an independent prognostic factor for biochemical recurrence in multivariable proportional hazards regression analyses (HR 0.99 per kg/m(2), 95% CI: 0.93-1.06). CONCLUSIONS: Compared with non-obese men, pathological tumor stage tended to be higher in obese men. Clinical relevance of this finding is unclear, because BMI was not an independent predictor of biochemical recurrence after radical prostatectomy.

Effect of tyrosine kinase inhibitor treatment of renal cell carcinoma on the accumulation of carbonic anhydrase IX-specific chimeric monoclonal antibody cG250.

OBJECTIVE: To investigate the effect of three different tyrosine kinase inhibitors (TKIs) on the biodistribution of chimeric monoclonal antibody (mAb) cG250, which identifies carbonic anhydrase IX (CAIX), in nude mice bearing human renal cell carcinoma (RCC) xenografts. TKIs represent the best, but still suboptimal treatment for metastatic RCC (mRCC) and combined therapy or sequential therapy might be beneficial. CAIX is abundantly over expressed in RCC and clinical trials have shown abundant and specific tumour accumulation of cG250. Combining a TKI with mAb cG250, involved in a different effector mechanism, might lead to improved tumour responses and survival in patients with mRCC. MATERIALS AND METHODS: Nude mice bearing human RCC xenografts were treated orally with 0.75 mg/day sunitinib, 1 mg/day vandetanib, 1 mg/day sorafenib or vehicle control for 7 or 14 days. At 7 days, mice were injected i.v. with 185 kBq/5 µg (125) I-cG250. Mice were killed at predetermined days and cG250 biodistribution was determined. Tumours were analysed by immunohistochemistry for the presence of endothelial cells, laminin, smooth muscle actin, CAIX expression and uptake of mAb cG250. RESULTS: While on TKI treatment, tumour uptake of cG250 decreased dramatically, tumour growth was slightly inhibited and vascular density decreased considerably as judged by various markers. When treatment was stopped at 7 days, there was robust neovascularization, mainly at the tumour periphery. Consequently, cG250 uptake also recovered, albeit cG250 uptake appeared to be restricted to the tumour periphery where vigorous neovascularization was visible. CONCLUSIONS: Simultaneous administration of a TKI and mAb cG250 severely compromised mAb accumulation. However, shortly after discontinuation of TKI treatment mAb accumulation was restored. Combined treatment strategies with TKI and mAb should be carefully designed.

Plasma selenium concentration and prostate cancer risk: results from the European Prospective Investigation into Cancer and Nutrition (EPIC).

BACKGROUND: Some evidence indicates that a low selenium intake may be associated with an increased risk of prostate cancer. OBJECTIVE: The aim of this study was to investigate the association of plasma selenium concentration with subsequent prostate cancer risk and to examine this association by stage and grade of disease and other factors. DESIGN: A nested case-control study was performed among men in the European Prospective Investigation into Cancer and Nutrition (EPIC). The association between plasma selenium concentration and prostate cancer risk was assessed in 959 men with incident prostate cancer and 1059 matched controls. RESULTS: Overall, plasma selenium concentration was not associated with prostate cancer risk; the multivariate relative risk for men in the highest fifth of selenium concentration compared with the lowest fifth was 0.96 (95% CI: 0.70, 1.31; P for trend = 0.25). There were no significant differences in the association of plasma selenium with risk when analyzed by stage or grade of disease. Similarly, the association of selenium with risk did not differ by smoking status or by plasma alpha- or gamma-tocopherol concentration. CONCLUSION: Plasma selenium concentration was not associated with prostate cancer risk in this large cohort of European men.

Carotenoid and vitamin intake, von Hippel-Lindau gene mutations and sporadic renal cell carcinoma.

OBJECTIVE: We investigated whether dietary carotenoid and vitamin intake and supplemental vitamin use were inversely associated with RCC risk and with Von Hippel-Lindau (VHL)-gene mutations in clear-cell renal cell carcinoma (RCC). METHODS: The Netherlands Cohort Study on diet and cancer (NLCS) includes 120,852 persons, who completed a self-administered food-frequency questionnaire in 1986. After 11.3 years of follow-up, 284 cases and a random sample of 4,095 persons (subcohort) with complete data were included in multivariable analyses using a case-cohort approach. VHL gene mutational analysis was complete for 225 cases. Rate ratios and corresponding 95% confidence intervals were estimated using Cox proportional hazard models, while adjusting for age, sex, smoking, body mass index, and a history of hypertension. RESULTS: We observed no association for dietary carotenoid and vitamin intake and RCC risk, and a somewhat increased risk with supplemental vitamin E, AD, and multivitamin use. Results were suggestive of higher RRs for alpha-carotene, beta-cryptoxanthin, folate, and supplemental vitamin C and multivitamin intake for wildtype VHL tumors compared to VHL-mutated tumors. CONCLUSIONS: There was no association of carotenoid, vitamin or supplemental vitamin intake and RCC risk. These associations should be investigated by others to confirm the current observations.

Coal tar in dermatology.

Coal tar is one of the oldest treatments for psoriasis and eczema. It has anti-inflammatory, antibacterial, antipruritic and antimitotic effects. The short-term side effects are folliculitis, irritation and contact allergy. Coal tar contains carcinogens. The carcinogenicity of coal tar has been shown in animal studies and studies in occupational settings. There is no clear evidence of an increased risk of skin tumors or internal tumors. Until now, most studies have been fairly small and they did not investigate the risk of coal tar alone, but the risk of coal tar combined with other therapies. New, well-designed, epidemiological studies are necessary to assess the risk of skin tumors and other malignancies after dermatological use of coal tar.

Treatment policy for psoriasis and eczema: a survey among dermatologists in the Netherlands and Belgian Flanders.

Today, many therapies are available for the treatment of psoriasis and eczema. One of the oldest topical therapies is coal tar. Coal tar has been used for decades, but over the past years, the use of coal tar has decreased for several reasons, including the supposed carcinogenicity of coal tar. We investigated the current and past treatment policies for psoriasis and eczema with special emphasis on the use of tar products; a postal survey was conducted among all dermatologists in two European countries: the Netherlands (n = 360) and the Flemish speaking part of Belgium (Flanders) (n = 328). This study was conducted as part of the ongoing LATER-study ("Late effects of coal tar treatment in eczema and psoriasis; the Radboud study"). All practising dermatologists received a questionnaire. Dermatologists were asked to describe their treatment policies in mild/moderate psoriasis, severe psoriasis, mild/moderate eczema and severe eczema. The response rate to the questionnaire was 62.5% for the Dutch dermatologists and 45.7% for the Flemish dermatologists. Almost all dermatologists prescribe topical corticosteroids. In eczema, most of the dermatologists prescribe the recently introduced calcineurin inhibitors (95%). Coal tar is a second choice topical therapy. Dutch dermatologists mainly use tar in the treatment of eczema (72% vs. 48% in Flanders), whereas in Flanders, tar is mainly prescribed in psoriasis (60% vs. 41% in Holland). Flemish dermatologists very frequently prescribe PUVA in psoriasis (93% vs. 63%). Topical treatment, especially topical corticosteroids, is the mainstay in psoriasis and eczema. Coal tar still is an important (second choice) therapy for the topical treatment of psoriasis and eczema, but its use varies from country to country. Despite the carcinogenicity of PUVA, this photochemotherapy is frequently prescribed by dermatologists, mainly in Flanders.

Risk factors for hypospadias.

Despite being one of the most common congenital defects in boys, the etiology of hypospadias remains largely unknown. In this case-referent study, we evaluated a wide spectrum of potential risk factors for hypospadias. Cases were identified from the hospital information system, and referents were recruited through the parents of the cases. Both parents of cases and referents completed written questionnaires that they received through the mail. Logistic regression analyses were used to assess the independent contribution of different factors to the risk of hypospadias. The final database included 583 cases and 251 referents. Hypospadias more often occurred in children whose father had hypospadias (OR=9.7; 95%CI: 1.3-74.0) and in children with a low birth weight (OR=2.3; 95%CI: 1.2-4.2). Indications for elevated risks were found when mothers were DES-daughters (OR=3.5; 95%CI: 0.8-15.6), fathers were subfertile (OR=1.8; 95%CI: 0.7-4.5), the parents had undergone fertility treatment (OR=2.3; 95%CI: 0.9-5.8), and in twin or triplet pregnancies (OR=2.0; 95%CI: 0.8-5.1). Maternal use of iron supplements (OR=2.2; 95%CI: 0.8-6.0), maternal smoking (OR=1.5; 95%CI: 1.0-2.4), paternal prescriptive drug use (OR=2.6; 95%CI: 1.1-6.6), and paternal exposure to pesticides (OR=2.1; 95%CI: 0.6-7.1) during the 3 months immediately prior to conception or in the first trimester of pregnancy also appeared to increase the risk of hypospadias. The associations found in this study support the hypothesis that genetic predisposition, placental insufficiency, and substances that interfere with natural hormones play a role in the etiology of hypospadias.

Correlation between quality of life and voiding variables in patients treated with percutaneous tibial nerve stimulation.

OBJECTIVE: To investigate the relationship between quality of life (QoL) and voiding variables in patients with lower urinary tract dysfunction treated with percutaneous tibial nerve stimulation (PTNS), as it is assumed that improvements in voiding will lead to a better QoL in such patients. PATIENTS AND METHODS: The study included 30 patients with urge urinary incontinence who were treated with PTNS; 24-h bladder diaries and QoL questionnaires (Short Form, SF-36, and incontinence-specific QoL) were completed at baseline and after PTNS. RESULTS: There was a significant correlation (P < 0.05) between the number of pads used and the SF-36 domains of physical and vitality, between the number of incontinence episodes and the SF-36 domains of physical and role physical, between nocturia and the SF-36 domains of general and mental health, between the mean voided volume and the SF-36 domains of role physical and final, and between the mean voided volume and the incontinence-specific QoL score. CONCLUSIONS: PTNS is useful for treating refractory urge incontinence and should at least be considered as a therapeutic alternative before resorting to aggressive surgery, as voiding and QoL variables significantly and quantifiably correlate in patients with refractory urge urinary incontinence who are treated with PTNS. Patients must have a reduction of >or = two pads/day before their QoL improves, and this might be the best definition of successful therapy for patients with urge urinary incontinence.

Posterior tibial nerve stimulation in the treatment of voiding dysfunction: urodynamic data.

OBJECTIVES: To determine urodynamic changes and predictive factors in patients with voiding dysfunction who underwent 12 percutaneous tibial nerve stimulations. METHODS: Thirty nine patients with chronic voiding dysfunction were enrolled in a prospective multicenter trial in the Netherlands (n = 19) and in Italy (n = 20). A 50% reduction in total catheterised volume per 24 hr was taken as a primary objective outcome measure. Patients' request for continuation of treatment was regarded as subjective success. Objective urodynamic parameters and bladder indices were determined. Odds ratios and their 95% confidence interval were computed as a measure for predictive power in order to reveal predictive factors (Pdet at Qmax, Qmax, BVE, and BCI). RESULTS: Primary outcome measure was obtained in 41%, an additional 26% reduced their 24 hr residuals with more than 25%. Fifty nine percent of patients chose to continue treatment. Detrusor pressure at maximal flow, cystometric residuals, and bladder indices improved significantly for all patients (P < 0.05). Patients with minor voiding dysfunction were more prone to notice success (Odds ratio: 0.73; 95% CI: 0.51-0.94). CONCLUSIONS: PTNS is a young treatment modality, minimally invasive, and easily accessible. It might be an attractive first line option for patients with (minor) voiding dysfunction.

Percutaneous tibial nerve stimulation in the treatment of overactive bladder: urodynamic data.

AIM: The aim of this study was to evaluate urodynamic changes after percutaneous tibial nerve stimulation (PTNS) for the treatment of complaints related to overactive bladder syndrome and to search for urodynamic-based predictive factors. METHODS: Ninety consecutive patients with symptoms related to overactive bladder syndrome were enrolled in this study. Patients underwent 12 PTNS sessions. For evaluating objective success, the primary outcome measure was a reduction in number of urinary leakage episodes of 50% or more per 24 hours. Patients' request for continuation of therapy was considered subjective success. This study focussed on urodynamic features at baseline and on changes found after 12 PTNS treatments. RESULTS: The objective success rate was 56% (leakages/24 hours). Subjective success rate was 64%. Frequency/volume chart data and quality of life scores improved significantly (P < 0.01). Pre- and posturodynamic data were available from 46 participants. Detrusor instabilities (DI) could be abolished in a few cases only. Increments in cystometric bladder capacity and in volume at DI were significant (P = 0.043 and 0.012, respectively). Subjects without detrusor instabilities at baseline were 1.7 times more prone to respond to PTNS (odds ratio, 1.75; 95% confidence interval [CI], 0.67-4.6). The more the bladder overactivity was pronounced, the less these patients were found to respond to PTNS, the area under the receiver operating curve was 0.644 (95% CI, 0.48-0.804). CONCLUSION: PTNS could not abolish DI. PTNS increased cystometric capacity and delayed the onset of DI. Cystometry seemed useful to select good candidates: patients without DI or with late DI onset proved to be the best candidates for PTNS.

Posterior tibial nerve stimulation in the treatment of idiopathic nonobstructive voiding dysfunction.

OBJECTIVES: To evaluate the effect of stimulation of the posterior tibial nerve in the treatment of voiding dysfunction. METHODS: Thirty-nine patients with chronic voiding dysfunction necessitating clean intermittent catheterization were enrolled in a prospective multicenter trial in the Netherlands (n = 19) and Italy (n = 20). They underwent 12 weekly sessions of posterior tibial nerve stimulation. Frequency/volume charts, an incontinence quality-of-life instrument, and the MOS 36-item Short-Form Health Survey were completed at 0 and 12 weeks. Subjective success was defined by the patient's positive response resulting in a request to continue treatment. Efficacy was based on analysis of the frequency/volume charts comparing the baseline values with the data at 12 weeks. A reduction of 50% or more in total catheterized volume was considered as an objective success (primary outcome measurement). RESULTS: Of the 39 patients, 23 (59%) chose to continue treatment. The frequency/volume charts showed a 50% decrease in total catheterized volume in 16 (41%) of 39 patients. Additionally, 10 patients (26%) noted a reduction of 25% to 50% in their total catheterized volume. For all patients, the total catheterized volume decreased by a mean of -228 mL (range -49 to -528). The incontinence quality-of-life instrument and Short-Form Health Survey parameters improved significantly. CONCLUSIONS: Percutaneous stimulation of the posterior tibial nerve seems to be an effective, minimally invasive option worth trying in patients with idiopathic voiding dysfunction. Improvement was seen in objective micturition parameters, as well as in subjective quality-of-life data.

Posterior tibial nerve stimulation in the treatment of urge incontinence.

AIMS: The objective of this study was to evaluate the effect of posterior tibial nerve stimulation (PTNS) for treatment of urge incontinence. METHODS: In a prospective multicentre study, 35 patients with complaints of urge incontinence underwent 12 weekly sessions of PTNS at one of five sites in the Netherlands and one site in Italy. Frequency/volume charts and I-QoL and SF-36 questionnaires were completed at 0 and 12 weeks. Success was analysed by using subjective and objective criteria. Overall subjective success was defined as the willingness to continue treatment, whereas objective success was defined as a significant decrease (to<50%) in total number of leakage episodes. RESULTS: Twenty-two patients (63%) reported a subjective success. Twenty-four patients (70%) showed a 50% or greater reduction in total number of leakage episodes. Sixteen (46%) of these-patients were completely cured (i.e., no leakage episodes) after 12 sessions. Quality of life parameters improved significantly. CONCLUSIONS: We conclude that posterior tibial nerve stimulation is an effective, minimally invasive option for treatment of patients with complaints of urge incontinence, as improvement was seen in subjective as well as objective parameters.

Baseline prostatic specific antigen does not predict the outcome of high energy transurethral microwave thermotherapy.

PURPOSE: We assessed the prognostic value of baseline prostate specific antigen (PSA) for outcome after high energy transurethral thermotherapy in patients with lower urinary tract symptoms. MATERIAL AND METHODS: Data were collected prospectively in 404 consecutive patients treated with high energy transurethral thermotherapy with the Prostatron device (EDAP-Technomed, Lyon, France). Patients were followed a minimum of 1 year. At baseline certain criteria were assessed, including pretreatment PSA, uroflowmetry, ultrasound measurement of prostatic volume, voided and post-void residual urine volume, and International Prostate Symptom Score (I-PSS) and quality of life scores. Outcome assessment included I-PSS, quality of life score and uroflowmetry of peak urine flow. Linear regression analyses were performed to correlate baseline PSA with improved clinical parameters at 12 months of followup. Logistic regression analyses and receiver operating characteristics curves characterized the ability of baseline PSA to discriminate patients with a more or less favorable outcome. RESULTS: An evident linear association was identified for prostate size at baseline and PSA. After 1 year 36 patients were treated again due to transurethral thermotherapy failure and 16 had died, which was not related to lower urinary tract symptoms or treatment for lower urinary tract symptoms. To include re-treated patients in the analyses we considered that their I-PSS, quality of life and peak urine flow values at 1 year were unchanged compared with baseline. Of the 388 evaluable patients an improvement of 50% or more in I-PSS, quality of life and peak urine flow was observed in 57%, 62% and 44%, respectively. Absolute mean changes at 1 year were -9.7, -2 and 5.2 ml. per second for I-PSS, quality of life and peak urine flow, respectively. Neither linear nor logistic regression analysis showed any clinically relevant correlation between baseline PSA and changes in I-PSS (r = -0.004), quality of life (r = -0.135) or peak urine flow (r = 0.105) at 1 year. Receiver operating characteristics curves failed to distinguish more or less favorable outcomes in all evaluated parameters. CONCLUSIONS: Pretreatment PSA cannot predict the clinical outcome after high energy transurethral thermotherapy.