Are video-urodynamics superior to traditional urodynamic studies in changing treatment decision with urinary symptoms?

Objective: To investigate the utility of video-urodynamic studies (VUDS) in patients with various urinary conditions and to evaluate if the addition of fluoroscopic imaging changes the treatment plans one would pursue if urodynamic studies (UDS) alone were performed as VUDS increases cost, radiation exposure, and patient discomfort. Patients and Methods: A retrospective chart review was conducted on all women who underwent VUDS from 2013 to 2015 at one institution. We hypothesised that the addition of the fluoroscopic images would not change the treatment plan. The protocol was conducted in two parts: (i) analysis of the patients' demographics, history, presentation, and VUDS results; then (ii) comparison of the documented VUDS diagnosis and plan with the theoretical diagnosis and plan of UDS alone. Results: Charts from 156 women were analysed. Fluoroscopic findings impacted the treatment plan in 60 patients. In 38 patients, fluoroscopic findings changed or added to the diagnosis. Vesico-ureteric reflux (VUR) was detected in 16 patients, nine were incidental findings (P < 0.001) in which there were no UDS findings of urinary retention (P = 0.01) or poor compliance (P = 0.02). Fluoroscopic findings of VUR significantly changed diagnosis (P < 0.001), but did not significantly change the treatment plan (P = 0.09). Conclusion: We conclude that fluoroscopic findings from VUDS do not add to or change the treatment plan. If there is a clinical concern for VUR, UDS with renal imaging would be able to detect findings or potential damage to the upper urinary tract without needing VUDS. Abbreviations: DESD: detrusor-external sphincter dyssynergia; LUT: lower urinary tract; POP: pelvic organ prolapse; PVR: post-void residual urine volume; SUFU: society of urodynamics, female pelvic medicine and urogenital reconstruction; (V)UDS: (video-) urodynamic study; UI: urinary incontinence.

Patient-Reported Outcome Measures (PROMs) in Pelvic Floor Disorders.

PURPOSE OF REVIEW: Patient-reported outcome measures (PROMs) are tools that are widely used by clinicians and researchers across different medical specialties. In this review, we examine the use of PROMs in the evaluation of female pelvic floor disorders (PFD). RECENT FINDINGS: PROM development in the assessment of urinary incontinence is more advanced than other pelvic disorders. Work is ongoing in the scientific community to improve currently available measures and create new robust tools where needed. Hundreds of PROMs are available for use in the evaluation of PFD, some more rigorously validated than others. They are used to screen for diseases, evaluate their impact on quality of life, determine the results of treatment, and measure patient's satisfaction with treatment. Careful consideration is required to choose the appropriate PROMs to care for a patient or include in a research study. The topic was reviewed in the Textbook of Female Urology and Urogynecology published in 2017. We reviewed recent literature (2015-2018) on the topic and summarized our findings.

Novel management approach to connecting tube erosion of artificial urinary sphincter.

Artificial urinary sphincter (AUS) erosion often involve the urethral cuff and is managed by complete or partial device removal. Abdominal wall erosion of AUS tubing has not been previously reported and its management is unknown. We report tube erosion (TE) of AUS successfully managed without device explant. An 81-year-old male with AUS for post-prostatectomy incontinence presented with TE at the site of inguinal incision without signs or symptoms of infection. The exposed tube was reduced and wound was closed after copious antibiotic solution irrigation. No complications were noted at 2 month follow up. AUS-TE can be successfully managed conservatively with antiseptic wound site irrigation and reinsertion in absence of infection.

Acid ceramidase upregulation in prostate cancer cells confers resistance to radiation: AC inhibition, a potential radiosensitizer.

Radiation resistance in a subset of prostate tumors remains a challenge to prostate cancer radiotherapy. The current study on the effects of radiation on prostate cancer cells reveals that radiation programs an unpredicted resistance mechanism by upregulating acid ceramidase (AC). Irradiated cells demonstrated limited changes of ceramide levels while elevating levels of sphingosine and sphingosine-1-phosphate. By genetically downregulating AC with small interfering RNA (siRNA), we observed radiosensitization of cells using clonogenic and cytotoxicity assays. Conversely, AC overexpression further decreased sensitivity to radiation. We also observed that radiation-induced AC upregulation was sufficient to create cross-resistance to chemotherapy as demonstrated by decreased sensitivity to Taxol and C(6) ceramide compared to controls. Lower levels of caspase 3/7 activity were detected in cells pretreated with radiation, also indicating increased resistance. Finally, utilization of the small molecule AC inhibitor, LCL385, sensitized PPC-1 cells to radiation and significantly decreased tumor xenograft growth. These data suggest a new mechanism of cancer cell resistance to radiation, through upregulation of AC that is, in part, mediated by application of the therapy itself. An improved understanding of radiotherapy and the application of combination therapy achieved in this study offer new opportunities for the modulation of radiation effects in the treatment of cancer.

Acid ceramidase inhibition: a novel target for cancer therapy.

During the last decade, sphingolipid deregulation, namely the balance between the pro-apoptotic molecule ceramide and the anti-apoptotic sphingolipid sphingosine-1-phosphate, has emerged as an important factor in cancer pathology and resistance to therapy. Thus, our research has been focused on developing drugs that are able to restore normal sphingolipid balance, precisely through increasing the levels of ceramide and decreasing sphingosine-1-phosphate. Particularly, inhibition of the ceramide metabolizing enzyme acid ceramidase, whose over-expression in cancer cells has been implicated in resistance to treatment, is proving to be an efficient and promising strategy. In this review, we consider our recent work with acid ceramidase inhibitors, in combination with radiation or gene therapy as a sensitizer that enhance cancer therapy.

The functional effects of acid ceramidase overexpression in prostate cancer progression and resistance to chemotherapy.

Among the many processes regulating cell death, ceramide signaling is a vital component. We previously determined that acid ceramidase (AC) is upregulated in 60% of primary prostate cancer (PCa) tissues, suggesting that AC may play a role in tumor development. In order to determine the significance of AC elevation, stable clones of DU145 cells with AC overexpression (AC-EGFP) were generated. Compared to controls (EGFP), AC-EGFP cells exhibited enhanced cell proliferation and migration. Subcutaneous injection of AC-EGFP cells into Nu/Nu mice resulted in larger tumor volumes compared to EGFP controls. Moreover, using the MTS viability assay, AC-EGFP cells were more resistant to cell death induced by doxorubicin, cisplatin, etoposide, gemcitabine or C6-ceramide. Conversely, knock down of AC using siRNA, sensitized AC-EGFP cells to these drugs. In addition, mass spectroscopic analysis of sphingolipids indicated that long chain ceramide levels were decreased in AC-EGFP cells treated with either doxorubicin or etoposide. In conclusion, this study implicates AC as a critical regulator of PCa progression by affecting not only tumor cell proliferation and migration but also responses to drug therapy, suggesting AC as a potential therapeutic target in advanced PCa.