2D ultrasound diagnosis of middle compartment prolapse: a multicenter study.

BACKGROUND: Recently, a specific methodology has been defined, using transperineal ultrasound, for the differential diagnosis of middle compartment prolapse [uterine prolapse (UP) or cervical elongation (CE) without UP] based on the difference in the pubis-uterine fundus distance at rest and with the Valsalva maneuver, with a cutoff point of 15 mm. The objective of this study was to validate the diagnostic utility of a ≥15 mm difference between the pubis-uterine fundus distance at rest and during the Valsalva maneuver to define UP in a multicenter study. METHODS: This prospective multicenter observational study included 94 patients (UP =51; CE without UP =43). The clinical examination was based on the International Continence Society Pelvic Organ Prolapse Quantification (ICS POP-Q) system for assessing pelvic organ prolapse (POP) and patients were candidates for corrective surgery of the middle compartment of the pelvic floor (correction of UP or CE without UP). The ultrasound study was performed by transperineal ultrasound (B-mode) with the patient undergoing dorsal lithotomy. The distance evaluation was performed in relation to the posteroinferior pubic margin in the midsagittal plane, with reference to the uterine fundus (established as the most distal hyperechogenic) line from the pubis to the uterine fundus at rest and with the Valsalva maneuver. We defined UP detected using UP as a difference of ≥15 mm between the pubis-uterine fundus distance at rest and with the Valsalva maneuver. Agreement between the clinical and ultrasound diagnosis of UP was assessed using the Cohen kappa coefficient of agreement and its 95% CIs. RESULTS: The ultrasound diagnosis of global UP at the three centers showed very good agreement, with a kappa index of 0.826 (0.71, 0.94). The agreement of ultrasound with the clinical diagnosis of UP using the ICS POP-Q system was very good for each of the hospitals [Hospital 1: 0.814 (0.64, 0.98), Hospital 2: 0.847 (0.64, 1) and Hospital 3: 0.824 (0.59, 1)]. CONCLUSIONS: A difference of ≥15 mm between the pubis-uterine fundus distance at rest and during the Valsalva maneuver for the diagnosis of UP presents very good agreement with the results of clinical evaluation with the ICS POP-Q system.

Digitation to Void: What Is the Significance of This Symptom?

OBJECTIVE: Digitation to void is defined as the need to apply manual pressure on the perineum or the vagina to assist with voiding. It has been associated with prolapse; however, there is little objective data concerning this symptom. Our aim was to determine the correlation between digitation to void, symptoms and signs of pelvic organ prolapse (POP), and urodynamic data. METHODS: This was a retrospective study that included a total of 1174 patients seen at a tertiary urogynecological unit. A standardized history was obtained from all patients followed by multichannel urodynamic testing, Pelvic Organ Prolapse Quantification scoring and 3-D/4-D translabial ultrasound. Stored 4-D translabial ultrasound volumes were obtained and analyzed at a later date. RESULTS: Digitation to void was present in 7% (n = 83) of our population. It is associated with primary symptoms of POP (odds ratio [OR], 25.75; confidence interval [CI], 8.08-82.05), clinically significant POP (OR, 5.62; CI, 2.25-14.02), and POP on ultrasound (OR, 5.39; CI, 2.67-10.88). Cystocele presented the strongest association, clinically (OR, 3.45; CI, 1.98-6.03) and on ultrasound (OR, 4.04; CI, 2.46-6.64). Digitation to void was also associated with symptoms of voiding dysfunction (OR, 6.38 [3.83-10.64]) and slower maximum urine flow rate centile (18.4 vs 24.9, P = 0.017). CONCLUSIONS: Digitation to void is strongly associated with primary symptoms of prolapse and of voiding dysfunction, clinically significant POP, and pelvic organ descent on ultrasound. It is also associated with objective voiding dysfunction. The strongest associations were found with cystocele, both clinically and on imaging.

Titanium dioxide food additive (E171) induces ROS formation and genotoxicity: contribution of micro and nano-sized fractions.

Since 1969, the European Union approves food-grade titanium dioxide (TiO2), also known as E171 colouring food additive. E171 is a mixture of micro-sized particles (MPs) and nano-sized particles (NPs). Previous studies have indicated adverse effects of oral exposure to E171, i.e. facilitation of colon tumour growth. This could potentially be partially mediated by the capacity to induce reactive oxygen species (ROS). The aim of the present study is to determine whether E171 exposure induces ROS formation and DNA damage in an in vitro model using human Caco-2 and HCT116 cells and to investigate the contribution of the separate MPs and NPs TiO2 fractions to these effects. After suspension of the particles in Hanks' balanced salt solution buffer and cell culture medium with either bovine serum albumin (BSA) or foetal bovine serum, characterization of the particles was performed by dynamic light scattering, ROS formation was determined by electron spin/paramagnetic resonance spectroscopy and DNA damage was determined by the comet and micronucleus assays. The results showed that E171, MPs and NPs are stable in cell culture medium with 0.05% BSA. The capacity for ROS generation in a cell-free environment was highest for E171, followed by NPs and MPs. Only MPs were capable to induce ROS formation in exposed Caco-2 cells. E171, MPs and NPs all induced single-strand DNA breaks. Chromosome damage was shown to be induced by E171, as tested with the micronucleus assay in HCT116 cells. In conclusion, E171 has the capability to induce ROS formation in a cell-free environment and E171, MPs and NPs have genotoxic potential. The capacity of E171 to induce ROS formation and DNA damage raises concerns about potential adverse effects associated with E171 (TiO2) in food.

Food-grade titanium dioxide exposure exacerbates tumor formation in colitis associated cancer model.

Colorectal cancer is the fourth worldwide cause of death and even if some dietary habits are consider risk factors, the contribution of food additives including foodgrade titanium dioxide (TiO2), designated as E171, has been poorly investigated. We hypothesized that oral E171 intake could have impact on the enhancement of colorectal tumor formation and we aimed to investigate if E171 administration could enhance tumor formation in a colitis associated cancer (CAC) model. BALB/c male mice were grouped as follows: a) control, b) E171, c) CAC and d) CAC + E171 group (n = 6). E171 used in this study formed agglomerates of 300 nm in water. E171 intragastric administration (5 mg/kg body weight/5 days/10 weeks) was unable to induce tumor formation but dysplastic alterations were observed in the distal colon but enhanced the tumor formation in distal colon (CAC + E171 group) measured by tumor progression markers. Some E171 particles were internalized in colonic cells of the E171 and CAC + E171 groups and both groups showed a decrease in goblet cells in the distal colon. However the CAC + E171 group showed a higher decrease of these cells that act as protection barrier in colon. These results suggest that E171 could worsen pre-existent intestinal diseases.