Pelvic radiation-induced urinary strictures: etiology and management of a challenging disease.

Radiation is a common treatment modality for pelvic malignancies. While it can be effective at cancer control, downstream effects can manifest months to years after treatment, leaving patients with significant morbidity. Within urology, a particularly difficult post-radiation consequence is urinary tract stricture, either of the urethra, bladder neck, or ureter. In this review, we will discuss the mechanism of radiation damage and treatment options for these potentially devastating urinary sequelae.

Ex-vivo ureteroscopy, laser lithotripsy, and stone basketing extraction of deceased donor kidney stones during machine perfusion preservation.

The incidence of nephrolithiasis in kidney donors is rare. The timing and treatment of nephrolithiasis in deceased donor kidneys are not well established. While some programs have proposed ex-situ rigid or flexible ureteroscopy treatment before transplantation, we report on two cases of kidney stones in the same deceased donor that we treated by flexible ureteroscopy and laser lithotripsy performed during the storage time on a hypothermic perfusion machine. Two deceased donor kidneys were found to have multiple kidney stones discovered on preprocurement CT imaging. The right kidney had less than five 2-3 mm stones, whereas the left had five to ten 1 mm stones with a single 7 mm stone. Both organs were placed on a hypothermic perfusion machine and maintained at a temperature of 4°C. An ex-vivo flexible ureteroscopy with laser lithotripsy and basket extraction was performed while the kidneys were maintained on Lifeport* perfusion machine. The cold ischemia time was 16.9 and 23.1 h. After 12 months of observational follow-up, neither recipient had nephrolithiasis, UTI, or other urologic complications. The creatinine values now are 1.17 and 2.44 mg/dL (103.4 and 215.7 µmol/L), respectively. Ex-vivo flexible ureteroscopy with laser lithotripsy and stone removal on machine-perfused kidneys appears to be safe and offers a good option to treat graft nephrolithiasis and prevent posttransplant complications. Ureteroscopy serves as a minimally invasive treatment option with direct stone removal. Performing this while on machine perfusion minimizes the ischemic time of the kidney and resultant complications or delays in graft function.

Sam68 guest STARs in TNF-α signaling.

In this issue of Molecular Cell, Ramakrishnan and Baltimore (2011) identify Sam68 as a TNFR1 docking protein required for proper activation of TNF-α signaling.

Sacral Neuromodulation: Determining Predictors of Success.

OBJECTIVE: To determine predictors of success for sacral neuromodulation in women with overactive bladder, urinary retention, and fecal incontinence. METHODS: A retrospective chart review was performed on women who underwent a staged sacral neuromodulation implantation between 2007 and 2018. Clinical and procedural characteristics were recorded. Presence of intraoperative motor responses in either all 4 or <4 electrodes were used to group women. Endpoints included completion of stage II implant, tined lead revision, and patient-reported success. RESULTS: In 198 women with a mean age of 62.9 years (SD+/- 14.7), completion of stage II implant occurred in 92.4% of women, and 83.3% of these women reported success at the first postoperative visit. Continued success at 6 months was reported in 70.3%. Lead revision was noted in 23.0%. Age >65 years (odds ratio [OR] = 0.2, 95% confidence interval [CI] = 0.06-0.8) and prior onabotulinumtoxinA (onaBoNT-A) (OR = 0.2, 95% CI = 0.06-0.9) were negative predictors for completion of stage II implant on multivariable analysis. Also, prior pelvic floor physical therapy was a significant negative predictor of postoperative patient-reported success on multivariable analysis (OR = 0.25, 95% CI = 0.1-0.6). There were no differences seen in women who had motor responses with either all 4 electrodes or <4 electrodes in any endpoint (P > .05). CONCLUSION: Patient age >65 and history of prior onaBoNT-A were associated with failure to complete stage II implant. Women with prior pelvic floor physical therapy were less likely to report success after sacral neuromodulation. Motor responses in <4 electrodes during lead testing did not impact patient-reported success.

Diet-induced oxalate nephropathy.

Oxalate nephropathy is a rare condition and may be overlooked due to lack of recognition and understanding of triggers. An 81-year-old man was sent to nephrologist because of significantly increased creatinine (1.5-1.9 mg/dL) noted for 3 months. He had well-controlled diabetes but no history of kidney disease. He had no chronic diarrhoea or intestinal surgery. He was a health-minded individual who had read extensively about benefit of antioxidants. Initial work-up was unrevealing. Within a few weeks after first visit, he developed acute symptomatic worsening kidney injury with nausea, vomiting and creatinine up to 6.8 mg/dL. Repeat examination of the urine sediment revealed casts containing calcium oxalate crystals. A deeper dietary history revealed widespread oxalate precursor consumption. A kidney biopsy confirmed oxalate nephropathy. Restriction of oxalate consumption combined with adequate hydration, oral calcium acetate resulted in partial renal recovery without need for haemodialysis.

Contemporary best practice in the management of staghorn calculi.

Staghorn calculi are complex renal stones that occupy the majority of the renal collecting system. These stones are associated with high morbidity and can lead to recurrent urinary tract infections, urosepsis, renal deterioration, and death if left untreated. Managing patients with staghorn calculi can be challenging. Fortunately, advances in technology and endourology techniques have enabled urologists to effectively treat these stones with minimal morbidity to the patient. This article describes the contemporary best practices in the initial evaluation, management, and follow up of patients with staghorn calculi to help the practicing urologist navigate this complex condition.

Targeting the sphingosine-1-phosphate axis in cancer, inflammation and beyond.

The bioactive lipid sphingosine-1-phosphate (S1P) is involved in multiple cellular signalling systems and has a pivotal role in the control of immune cell trafficking. As such, S1P has been implicated in disorders such as cancer and inflammatory diseases. This Review discusses the ways in which S1P might be therapeutically targeted - for example, via the development of chemical inhibitors that target the generation, transport and degradation of S1P and via the development of specific S1P receptor agonists. We also highlight recent conflicting results observed in preclinical studies targeting S1P and discuss ongoing clinical trials in this field.

Detection of protein analytes via nanoparticle-based bio bar code technology.

We describe a new format for the recently introduced bio bar code technology, which improves the dose response over 10,000-fold and thereby makes this technique analytically useful. Unlike other ultrasensitive protein detection methods, such as immuno-PCR or immuno-RCA, the bio bar code technique does not employ any enzymes to achieve detection limits in the attomolar range. By sandwiching a target between a magnetic bead and an amplifier nanoparticle, a multiplicity of bar code oligonucleotides are released for each captured target analyte. These surrogate bar code targets are then hybridized to microarrays and detected with silver-amplified gold nanoparticle probes. Using PSA detection as a model, we demonstrate a linear dose response over at least 4 orders of magnitude in both target concentration and concomitant signal and a 1000-fold improvement in detection limit compared to the best ELISA system.