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Background: Lower urinary tract symptoms (LUTSs) are a common complaint in adult and elderly men with bladder outlet obstruction, and have a considerable impact on their quality of life. Symptoms affect storage, voiding and post micturition stages. Among the latter, a feeling of incomplete emptying is one of the most bothersome for the patients; a condition that in turn contributes to affect urinary urgency, nocturia and frequency. Common recommendations include self-management practices (e.g., control of fluid intake, double-voiding and distraction techniques) to relieve patients' symptoms, whose effectiveness, however, is under debate. Methods: In this report we describe two pioneering procedures to favor bladder residual content voiding in people complaining of LUTS disorders. The first is based on motor imagery and the second on the use of odors. The beneficial effects of Mental imagery techniques on various tasks (e.g., in the treatment of several pathological conditions or as valid mnemonics aids have a long tradition and have received consistently experimental support. Thus, a patient (a 68-year-old Caucasian man) complaining of LUTS was trained to use a motor imagery technique (building up a visual image comprising the bladder, the detrusor muscle and the urethra, and to imagine the detrusor muscle contracting and the flow of urine expelled) for 90 days and two odors (coffee and a lavender scented cleanser) for 10 days, as a trigger for micturition. He was asked to record—immediately after the first morning micturition—the time interval between the first (free) and the second (cued) micturition. Results: Reported data suggest the efficacy of motor imagery in favoring the bladder residual urine voiding in a few minutes (M = 4.75 min.) compared to the control condition, i.e., the baseline of the patient (M = 79.5 min.), while no differences between the odor-based procedures (M 1st odorant = 70.6 min.; M 2nd odorant = 71.1 min) and the latter were observed. Conclusions: A procedure based on an imagery technique may, therefore, be of general value—as a suggested protocol—and accordingly can be applicable to clinical settings. An olfactory bladder control hypothesis cannot, however, be ruled out and is discussed as a promising future line of research. [ABSTRACT FROM AUTHOR]

This is a retrospective study of our experience with Gentamicin intravesical instillation as therapy and prophylaxis in patients with lower urinary tract infections (UTIs) undergoing clean intermittent catheterization because of a neurogenic bladder. It is an alternative therapy when all other systemic treatments have failed as it is still an off-label prescription. [ABSTRACT FROM AUTHOR]

Background: Antimuscarinics (AMs) represent the mainstay of treatment for storage lower urinary tract symptoms (LUTS) but few data are available on their impact in multiple sclerosis (MS) patients. Objective: To assess effectiveness and tolerability of AMs in MS patients with neurogenic detrusor overactivity (NDO). Methods: Sixty consecutive outpatients, who started treatment with AMs at one centre, were recruited. The primary endpoint was change in Patient's Perception of Intensity of Urgency Scale (PPIUS) at 6 months; secondary endpoints were post-void residual urine (PVR) and pads used daily. Incidence and severity of adverse events (AEs) were recorded. Results: Significant reduction (p < 0.001) of mean PPIUS and pads use were detected, as well as a significant increase (p < 0.001) of PVR (143 ± 42 ml). AEs, recorded in 53% of patients, were frequently multiple and caused suspension of AM in 10% of cases, mainly for xerostomia, which has been the commonest AE (26.6%). Neurological AEs appeared in 11.7% of subjects, mostly with oxybutynin. Worsening/onset of voiding LUTS, reported by 8.3% of MS, resulted to be the unique AE correlated to AM dosage. Conclusion: This study suggests that AMs are effective in MS patients, but their use should be tailored on every patient as even low dosages can be poorly tolerated. AEs, including neurological ones, are common. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: Pregnancy in women with spinal-cord injury (SCI) poses a clinical challenge. We hypothesized that changes in the management of neurogenic bladder during pregnancy are commonly required and should receive more attention.Methods: Data were collected by retrospective analysis of medical records and via cross-sectional survey of 52 women with SCI, representing 67 pregnancies, at ten Italian neurourological clinics. All participants provided informed consent.Results: Between 1976 and 2013, 39 participants had one child, 11 had two children, and two had three children. Mean age at the time of SCI was 18 years and at the time of first pregnancy was 30 years. Delivery occurred from weeks 32 to 40 in 98% of first and second pregnancies, and 94% of neonates were healthy. Oxybutynin was used by four women during five pregnancies, which resulted in delivery of healthy babies. Intermittent catheterization was used before 54% of first pregnancies and 39% of second pregnancies. Bladder management was altered during 45% of these pregnancies, and the most common changes were increased use or frequency of intermittent catheterization or use of an indwelling catheter. Urinary tract infections occurred in 48% of pregnancies, and an irregular course was reported in 13% of pregnancies mainly related to tetraplegia and urological complications.Conclusions: Pregnancy in women with SCI generally has good outcomes and limited risks but frequently necessitates changes in the management of neurogenic bladder. High levels of awareness and focused monitoring of bladder issues are recommended. [ABSTRACT FROM AUTHOR]

Brush border Myosin Ia ( MYO1A) has been shown to be frequently mutated in colorectal tumors with microsatellite instability (MSI) and to have tumor suppressor activity in intestinal tumors. Here, we investigated the frequency of frameshift mutations in the A8 microsatellite in exon 28 of MYO1A in MSI gastric and endometrial tumors and found a high mutation rate in gastric (22/47; 46.8%) but not endometrial (3/48; 6.2%) tumors. Using a regression model, we show that MYO1A mutations are likely to confer a growth advantage to gastric, but not endometrial tumors. The mutant MYO1A7A protein was shown to lose its membrane localization in gastric cancer cells and a cycloheximide-chase assay demonstrated that the mutant MYO1A7A protein has reduced stability compared to the wild type MYO1A. Frequent MYO1A promoter hypermethylation was also found in gastric tumors. Promoter methylation negatively correlates with MYO1A mRNA expression in a series of 58 non-MSI gastric primary tumors (Pearson's r = −0.46; p = 0.0003) but not in a cohort of 54 non-MSI endometrial tumors and treatment of gastric cancer cells showing high MYO1A promoter methylation with the demethylating agent 5-aza-2′-deoxycytidine, resulted in a significant increase of MYO1A mRNA levels. We found that normal gastric epithelial cells, but not normal endometrial cells, express high levels of MYO1A. Therefore, when considered together, our findings suggest that MYO1A has tumor suppressor activity in the normal gastric epithelium but not in the normal endometrium and inactivation of MYO1A either genetically or epigenetically may confer gastric epithelial cells a growth advantage. [ABSTRACT FROM AUTHOR]

The loss of the epithelial architecture and cell polarity/differentiation is known to be important during the tumorigenic process. Here we demonstrate that the brush border protein Myosin Ia (MYO1A) is important for polarization and differentiation of colon cancer cells and is frequently inactivated in colorectal tumors by genetic and epigenetic mechanisms. MYO1A frame-shift mutations were observed in 32% (37 of 116) of the colorectal tumors with microsatellite instability analyzed, and evidence of promoter methylation was observed in a significant proportion of colon cancer cell lines and primary colorectal tumors. The loss of polarization/differentiation resulting from MYO1A inactivation is associated with higher tumor growth in soft agar and in a xenograft model. In addition, the progression of genetically and carcinogen-initiated intestinal tumors was significantly accelerated in Myo1a knockout mice compared with Myo1a wild-type animals. Moreover, MYO1A tumor expression was found to be an independent prognostic factor for colorectal cancer patients. Patients with low MYO1A tumor protein levels had significantly shorter disease-free and overall survival compared with patients with high tumoral MYO1A (logrank test P = 0.004 and P = 0.009, respectively). The median time-to-disease recurrence in patients with low MYO1A was 1 y, compared with >9 y in the group of patients with high MYO1A. These results identify MYO1A as a unique tumor-suppressor gene in colorectal cancer and demonstrate that the loss of structural brush border proteins involved in cell polarity are important for tumor development. [ABSTRACT FROM AUTHOR]

Although deregulation of EPHB signaling has been shown to be an important step in colorectal tumorigenesis, the role of EPHB6 in this process has not been investigated. We found here that manipulation of EPHB6 levels in colon cancer cell lines has no effect on their motility and growth on a solid substrate, soft agar or in a xenograft mouse model. We then used an EphB6 knockout mouse model to show that EphB6 inactivation does not efficiently initiate tumorigenesis in the intestinal tract. In addition, when intestinal tumors are initiated genetically or pharmacologically in EphB6+/+ and EphB6−/− mice, no differences were observed in animal survival, tumor multiplicity, size or histology, and proliferation of intestinal epithelial cells or tumor cells. However, reintroduction of EPHB6 into colon cancer cells significantly reduced the number of lung metastasis after tail-vein injection in immunodeficient mice, while EPHB6 knockdown in EPHB6-expressing cells increased their metastatic spread. Consistently, although EPHB6 protein expression in a series of 130 primary colorectal tumors was not associated with patient survival, EPHB6 expression was significantly lower in lymph node metastases compared to primary tumors. Our results indicate that the loss of EPHB6 contributes to the metastatic process of colorectal cancer. [ABSTRACT FROM AUTHOR]

EPH signaling deregulation has been shown to be important for colorectal carcinogenesis and genome-wide sequencing efforts have identified EPHA3 as one of the most frequently mutated genes in these tumors. However, the role of EPHA3 in colorectal cancer has not been thoroughly investigated. We show here that ectopic expression of wild type EPHA3 in colon cancer cells did not affect their growth, motility/invasion or metastatic potential in vivo. Moreover, overexpression of mutant EPHA3 or deletion of the endogenous mutant EPHA3 in colon cancer cells did not affect their growth or motility. EPHA3 inactivation in mice did not initiate the tumorigenic process in their intestine, and had no effects on tumor size/multiplicity after tumor initiation either genetically or pharmacologically. In addition, immunohistochemical analysis of EPHA3 tumor levels did not reveal associations with survival or clinicopathological features of colorectal cancer patients. In conclusion, we show that EPHA3 does not play a major role in colorectal tumorigenesis. These results significantly contribute to our understanding of the role of EPH signaling during colorectal carcinogenesis, and highlighting the need for detailed functional studies to confirm the relevance of putative cancer driver genes identified in sequencing efforts of the cancer genome. [ABSTRACT FROM AUTHOR]