A methylation assay for the detection of non-muscle-invasive bladder cancer (NMIBC) recurrences in voided urine

What's known on the subject? and What does the study add? Multiple studies report on the detection of methylation in voided urine samples as a possible approach for the follow‐up of non‐muscle invasive bladder cancer patients. Previous studies analyze methylation gene panels in a mixture of primary and recurrent tumours. As primary tumours are larger than recurrent tumours and thus easier to detect in urine, validation of methylation markers in urine samples from patients with primary tumours will result in a test sensitivity that does not reflect the true sensitivity of the assay. This study is the first to select a subset of genes specifically methylated in non‐muscle invasive bladder cancer recurrences and validates the gene panel in two independent sets of urine samples from recurrent patients, thus simulating the disease course according to the clinical presentation.

OBJECTIVE

• ? To develop a methylation‐specific multiplex ligation‐dependent probe amplification (MS‐MLPA) assay for the detection of non‐muscle invasive bladder cancer (NMIBC) recurrences in voided urine.

PATIENTS AND METHODS

• ? Genes frequently methylated in NMIBC tumours (n= 37) were selected to develop a BC‐specific MS‐MLPA assay.
• ? Genes methylated in blood from patientswith BC (n= 29) and genes methylated in urine from patients with no history of BC (n= 46) were excluded.
• ? A four‐gene panel with the highest predictive value was selected from the initial assay. This four‐gene panel was tested and validated on urine from patients with a histologically confirmed recurrence (n= 68 test set; n= 49 validation set) and urine samples from patients without BC (n= 91, test set) and urine from recurrence‐free BC (rec‐free BC) patients (n= 60, validation set).
• ? A model was developed to predict the probability of having a recurrence based on methylation of the four‐gene panel and a threshold probability with the highest sensitivity and specificity was determined.
• ? The outcome of the model was validated on BC urine samples (n= 65) and on urine samples from rec‐free BC patients (n= 29).

RESULTS

• ? The BC MS‐MLPA assay consisted of 23 methylation probes. The selected four‐gene panel included: APC_a, TERT_a, TERT_b, and EDNRB. This panel reached an area under the receiver operating characteristic curve (AUC) of 0.82 (test set) and AUC 0.69 (validation set). Sensitivity and specificity for the detection of a concomitant tumour were 63.3% and 58.3% respectively (test set) and 72.3% and 55.2%, respectively (validation set).

CONCLUSIONS

• ? We have developed a methylation detection assay specifically for the detection of recurrences in patients with NMIBC in voided urine.
• ? The findings are promising and improvement of this test could eventually contribute to a more individualized patient friendly surveillance.

     

The prevalence of pelvic organ prolapse symptoms and signs and their relation with bladder and bowel disorders in a general female population

Introduction and hypothesis  In selected populations, pelvic organ prolapse (POP) was associated with bladder/bowel symptoms, but data on the general female population are lacking. Our aim was to obtain normative data on the prevalence of POP and pelvic floor dysfunction (PFD) symptoms and signs and to identify associations. Methods  Validated questionnaires on POP and PFD (urogenital distress inventory, (UDI) and defaecation distress inventory (DDI)) were sent to a general population of 2,979 women (aged 45–85 years). Data were analysed using the Kruskal–Wallis test, chi square test and Spearman’s rank correlation coefficient. Results  Response rate was 62.7%. Associations between POP stage and parity (0.002) and vaginal bulging (<0.001) are significant. Anatomical locations of POP and PFD symptoms correlated significantly with incontinence of flatus, feeling anal prolapse, manual evacuation of stool, vaginal bulging, constipation and pain during faecal urge (p ≤ 0.005). Conclusions  Strategies should be developed to alleviate obstructive bowel disorders associated with POP. Summary  POP was strongly associated with obstructive bowel disorders. Therefore, preventive strategies should be developed.     

The neglect of child neglect: a meta-analytic review of the prevalence of neglect

Purpose

The aim of the current meta-analysis was to provide an estimate of the prevalence of physical and emotional neglect by integrating prevalence figures from the body of research reporting on neglect. An attempt was also made to unravel the substantial variation in prevalence figures reported in primary studies by analyzing the effects of procedural factors and sample characteristics on combined prevalence rates.

Methods

Studies providing prevalence rates of child neglect were searched using electronic databases, exploring specialized journals, and by searching references of publications for other relevant studies. Data were extracted using a coding system. Intercoder reliability was satisfactory. A comprehensive meta-analysis was conducted.

Results

Child physical neglect prevalence rates were found for 13 independent samples with a total of 59,406 participants, and child emotional neglect prevalence rates were found for 16 independent samples with a total of 59,655 participants. The overall estimated prevalence was 163/1,000 for physical neglect, and 184/1,000 for emotional neglect, with no apparent gender differences. The influence of research design factors on the prevalence of physical neglect was more pronounced than on the prevalence of emotional neglect. Studies on physical neglect in ‘low-resource’ countries were conspicuously absent.

Conclusions

Child neglect is a problem of considerable extent, but seems to be a neglected type of maltreatment in scientific research. This is illustrated by the deplorable dearth of studies on child neglect, especially in low-resource countries. Recommendations for the design of future prevalence studies are proposed.     

Microbiological and clinical effects of chlorhexidine enclosed in fixtures of 3I-Titamed implants

This double-blind study used a split-mouth design to investigate the microbiological and clinical effects of 0.2% chlorhexidine enclosed in fixtures. Twelve patients had 46 fixtures implanted. At second-stage surgery, a microbiological sample (baseline sample) of the inner parts of the fixtures was taken. Then, a 0.2% chlorhexidine solution was applied into the inner space of 23 fixtures (test group), and in 23 fixtures saline was applied (control group). Abutments were installed and gingival index, plaque index and crevicular fluid flow were monitored weekly. After 6 weeks, a second microbiological sample of the inner part of the fixtures was taken. At baseline, viable bacteria were detected within 46% of the fixtures. After weeks, bacteria were found in 87% of the fixtures. The numbers of bacteria in the control group were significantly higher than those in the test group. The results indicate that, after first-stage surgery, contamination of the inner spaces of the fixtures is commonplace. Application of a 0.2% chlorhexidine solution at second-stage surgery inhibits growth or acquisition of bacteria in the fixtures. In both test and control groups, the crevicular fluid flow as well as the gingival index decreased during the experimental period. At 4, 5, and 6 weeks after chlorhexidine application, these values in the test group appeared lower, but did not attain statistical significance.