Benjamin K. Canales

A pilot study on the early use of the vacuum erection device after radical retropubic prostatectomy

To evaluate the effect of the early use of the vacuum erection device (VED) on erectile dysfunction (ED) and penile shortening after radical retropubic prostatectomy (RP), as these are important concerns for men choosing among treatment alternatives for localized prostate cancer.

ALFUZOSIN STONE EXPULSION THERAPY FOR DISTAL URETERAL CALCULI: A DOUBLE-BLIND PLACEBO- CONTROLLED STUDY

PURPOSE We evaluated the efficacy of alfuzosin as medical expulsive therapy for distal ureteral stone passage. MATERIALS AND METHODS A total of 76 patients with a distal ureteral calculus provided consent for the study. Patients were randomized between placebo and study medication, and investigators and patients were blinded to the randomization scheme. Followup was done on a weekly basis and continued until the patient was rendered stone-free. The patient blood pressure, discomfort level, stone position on imaging, number of remaining pills and any adverse events were assessed. Statistical analysis was performed with the Student t test with p <0.05 considered significant. RESULTS The overall spontaneous stone passage rate was 75%, including 77.1% for placebo and 73.5% for alfuzosin (p = 0.83). Mean +/- SD time needed to pass the stone was 8.54 +/- 6.99 days for placebo vs 5.19 +/- 4.82 days for alfuzosin. (p = 0.003). There was no difference in the size or volume of stones that passed spontaneously between the placebo and alfuzosin arms, as measured on baseline computerized tomography (4.08 +/- 1.17 and 3.83 +/- 0.95 mm, p = 0.46) and by a digital caliper after stone expulsion (3.86 +/- 1.76 and 3.91 +/- 1.06 mm, respectively, p = 0.57). When comparing the improvement from the baseline pain score, the alfuzosin arm experienced a greater decrease in pain score in the days after the initial emergency department visit to the date of stone passage (p = 0.0005). CONCLUSIONS Alfuzosin improves the patient discomfort associated with stone passage and decreases the time to distal ureteral stone passage but it does not increase the rate of spontaneous stone passage.

Prevalence and effect of varicoceles in an elderly population

OBJECTIVES The prevalence of a varicocele in the adolescent and young adult populations is approximately 15%. Because other varicose veins increase in prevalence with advanced age, we hypothesized that the incidence of varicoceles in the elderly population would be greater and might affect testicular size, consistency, and function. METHODS As part of a prostate cancer screening program, we prospectively evaluated 354 men (mean age 60.7 years) by physical examination for the presence of a varicocele, testicular size, and consistency, and measured the serum testosterone level. RESULTS A varicocele was present bilaterally in 19.8% (70 of 354), left sided only in 22.0% (78 of 354), and right sided only in 1.1% (4 of 354) of patients. Decreased testosterone levels correlated with older age (P = 0.001) and the presence of bilaterally soft testes (P = 0.02) but not the presence of a varicocele. Testes in men with bilateral varicoceles were significantly smaller (P = 0.001) and softer (P = 0.001) than in men without varicoceles. Higher grade varicoceles were more likely to be associated with soft testes (P = 0.001) than were lower grade varicoceles. CONCLUSIONS The 42% prevalence of varicoceles in our elderly population was greater than that for historic control younger populations, suggesting either an increase with age or examiner sensitivity bias. Varicoceles in the elderly, especially when bilateral, significantly affect testicular consistency (softer) and testicular size (smaller), but do not directly decrease serum testosterone levels. The presence of bilaterally soft testes in elderly men indicates bilateral gonadal dysfunction and may be a physical examination finding associated with decreased serum testosterone.

Alpha blockers for treatment of ureteric stones: systematic review and meta-analysis.

Objective To investigate the efficacy and safety of alpha blockers in the treatment of patients with ureteric stones. Design Systematic review and meta-analysis. Data sources Cochrane Central Register of Controlled Trials, Web of Science, Embase, LILACS, and Medline databases and scientific meeting abstracts to July 2016. Review methods Randomized controlled trials of alpha blockers compared with placebo or control for treatment of ureteric stones were eligible.Two team members independently extracted data from each included study. The primary outcome was the proportion of patients who passed their stone. Secondary outcomes were the time to passage; the number of pain episodes; and the proportions of patients who underwent surgery, required admission to hospital, and experienced an adverse event. Pooled risk ratios and 95% confidence intervals were calculated for the primary outcome with profile likelihood random effects models. Cochrane Collaboration’s tool for assessing risk of bias and the GRADE approach were used to evaluate the quality of evidence and summarize conclusions. Results 55 randomized controlled trials were included. There was moderate quality evidence that alpha blockers facilitate passage of ureteric stones (risk ratio 1.49, 95% confidence interval 1.39 to 1.61). Based on a priori subgroup analysis, there seemed to be no benefit to treatment with alpha blocker among patients with smaller ureteric stones (1.19, 1.00 to 1.48). Patients with larger stones treated with an alpha blocker, however, had a 57% higher risk of stone passage compared with controls (1.57, 1.17 to 2.27). The effect of alpha blockers was independent of stone location (1.48 (1.05 to 2.10) for upper or middle stones; 1.49 (1.38 to 1.63) for lower stones). Compared with controls, patients who received alpha blockers had significantly shorter times to stone passage (mean difference −3.79 days, −4.45 to −3.14; moderate quality evidence), fewer episodes of pain (−0.74 episodes, −1.28 to −0.21; low quality evidence), lower risks of surgical intervention (risk ratio 0.44, 0.37 to 0.52; moderate quality evidence), and lower risks of admission to hospital (0.37, 0.22 to 0.64; moderate quality evidence). The risk of a serious adverse event was similar between treatment and control groups (1.49, 0.24 to 9.35; low quality evidence). Conclusions Alpha blockers seem efficacious in the treatment of patients with ureteric stones who are amenable to conservative management. The greatest benefit might be among those with larger stones. These results support current guideline recommendations advocating a role for alpha blockers in patients with ureteric stones. Systematic review registration PROSPERO registration No CRD42015024169.

Unified theory on the pathogenesis of Randall’s plaques and plugs

Kidney stones develop attached to sub-epithelial plaques of calcium phosphate (CaP) crystals (termed Randall’s plaque) and/or form as a result of occlusion of the openings of the Ducts of Bellini by stone-forming crystals (Randall’s plugs). These plaques and plugs eventually extrude into the urinary space, acting as a nidus for crystal overgrowth and stone formation. To better understand these regulatory mechanisms and the pathophysiology of idiopathic calcium stone disease, this review provides in-depth descriptions of the morphology and potential origins of these plaques and plugs, summarizes existing animal models of renal papillary interstitial deposits, and describes factors that are believed to regulate plaque formation and calcium overgrowth. Based on evidence provided within this review and from the vascular calcification literature, we propose a “unified” theory of plaque formation—one similar to pathological biomineralization observed elsewhere in the body. Abnormal urinary conditions (hypercalciuria, hyperoxaluria, and hypocitraturia), renal stress or trauma, and perhaps even the normal aging process lead to transformation of renal epithelial cells into an osteoblastic phenotype. With this de-differentiation comes an increased production of bone-specific proteins (i.e., osteopontin), a reduction in crystallization inhibitors (such as fetuin and matrix Gla protein), and creation of matrix vesicles, which support nucleation of CaP crystals. These small deposits promote aggregation and calcification of surrounding collagen. Mineralization continues by calcification of membranous cellular degradation products and other fibers until the plaque reaches the papillary epithelium. Through the activity of matrix metalloproteinases or perhaps by brute physical force produced by the large sub-epithelial crystalline mass, the surface is breached and further stone growth occurs by organic matrix-associated nucleation of CaOx or by the transformation of the outer layer of CaP crystals into CaOx crystals. Should this theory hold true, developing an understanding of the cellular mechanisms involved in progression of a small, basic interstitial plaque to that of an expanding, penetrating plaque could assist in the development of new therapies for stone prevention.

Proteome of Human Calcium Kidney Stones

OBJECTIVES Idiopathic calcium oxalate (CaOx) stones are believed to develop attached to papillary subepithelial deposits called Randalls plaques. Calcium phosphate (CaP) stones, conversely, are thought to arise within the inner medullary collecting ducts, enlarging and damaging surround tubular structures as they expand. If this is true, we theorize that differences will be seen within the organic portion (matrix) of CaOx stones compared with CaP stones using a mass spectroscopy (MS) approach. METHODS From a cohort of 47 powdered stones, 25 calculi (13 CaOx, 12 CaP) were confirmed to contain a dominant mineral content of >80% by powder x-ray diffraction. Matrix proteins were then extracted, purified, and digested. Peptide tandem MS data were acquired, and spectra were searched against a large human protein database to identify protein matches. RESULTS No significant differences were seen between pattern profiles of CaOx and CaP stones. However, variations in protein expression patterns were seen within individual CaOx (monohydrate and dihydrate) and CaP (apatite and brushite) mineral subtypes, suggesting a relationship between crystal-surface binding properties and matrix composition. Both groups contain a large number of inflammatory proteins and a catalog of common proteins is included. CONCLUSIONS Calcium kidney stone matrix contains hundreds of proteins and is predominated by proteins associated with inflammatory response. Many of the same proteins were identified in both CaOx and CaP stones, suggesting inflammation as a unifying origin or a common secondary role in calcium stone pathogenesis.

Second prize: Comprehensive proteomic analysis of human calcium oxalate monohydrate kidney stone matrix

BACKGROUND AND PURPOSE Previous efforts to identify the protein content of stone matrix have been limited by the lack of technology necessary to analyze the highly insoluble protein-crystalline complex. Our study objective is to characterize the matrix of calcium oxalate monohydrate (COM) stones using a comprehensive proteomics approach. MATERIALS AND METHODS Seven pure COM stones were powdered, and proteins were extracted using four different buffer solutions. Detergent cleanup spin columns or concentrators were used to remove detergent and to exchange buffers before trypsin digestion. Tryptic peptides were analyzed with reversed-phase, high-performance liquid chromatography (RP-HPLC) and tandem mass spectrometry (MS/MS) using a QSTAR Pulsar i quadrapole time of flight mass spectrometer. Tandem mass spectra were searched against National Center for Biotechnology Information human nonredundant database using ProteinPilot 1.0 software (Applied Biosystems, Inc.) for protein hits; peptide MS/MS spectra were manually inspected. RESULTS Of the four buffers, only 2% sodium dodecyl sulfate (SDS) samples had normal HPLC and MS/MS elution patterns. We identified 68 distinct proteins with 95% confidence. More than 50 of the proteins have not been previously identified in stone matrix. Of particular note, a significant number of inflammatory proteins were identified, including immunoglobulins, defensin -3, clusterin, complement C3a, kininogen, and fibrinogen. CONCLUSIONS SDS reducing buffer was efficient at solubilizing proteins from stone matrix for further MS-based proteomic analysis. A variety of cellular, structural, and plasma proteins comprise COM stone matrix. Several of the stone proteins are involved in cell injury pathways, which suggests that inflammation plays a role in human COM stone formation.

Steatorrhea and Hyperoxaluria Occur after Gastric Bypass Surgery in Obese Rats Regardless of Dietary Fat or Oxalate

PURPOSE We determined the effect of dietary fat and oxalate on fecal fat excretion and urine parameters in a rat model of Roux-en-Y gastric bypass surgery. MATERIALS AND METHODS Diet induced obese Sprague-Dawley® rats underwent sham surgery as controls (16), or Roux-en-Y gastric bypass surgery (19). After recovery, rats had free access to a normal calcium, high fat (40%) diet with or without 1.5% potassium oxalate for 5 weeks and then a normal (10%) fat diet for 2 weeks. Stool and urine were collected after each period. Fecal fat was determined by gas chromatography and urine metabolites were evaluated by assay spectrophotometry. RESULTS Daily fecal fat excretion remained low in controls on either diet. However, Roux-en-Y gastric bypass rats ingested a food quantity similar to that of controls but had eightfold higher fecal fat excretion (p <0.001) and heavier stools (p = 0.02). Compared to controls, gastric bypass rats on the high fat diet with potassium oxalate had a fivefold increase in urine oxalate excretion (p <0.001), while gastric bypass rats without potassium oxalate had a twofold increase in urine calcium (p <0.01). Lowering dietary fat in gastric bypass rats with potassium oxalate led to a 50% decrease in oxalate excretion (p <0.01), a 30% decrease in urine calcium and a 0.3 U increase in urine pH (p <0.001). CONCLUSIONS In this Roux-en-Y gastric bypass model high fat feeding resulted in steatorrhea, hyperoxaluria and low urine pH, which were partially reversible by lowering the dietary fat and oxalate content. Roux-en-Y gastric bypass rats on normal fat and no oxalate diets excreted twice as much oxalate as age matched, sham operated controls. Although Roux-en-Y gastric bypass hyperoxaluria appears primarily mediated by gut and diet, secondary causes of oxalogenesis from liver or other mechanisms deserve further exploration.

Genetic basis of renal cellular dysfunction and the formation of kidney stones.

Nephrolithiasis is a result of formation and retention of crystals within the kidneys. The driving force behind crystal formation is urinary supersaturation with respect to the stone-forming salts, which means that crystals form when the concentrations of participating ions are higher than the thermodynamic solubility for that salt. Levels of supersaturation are kept low and under control by proper functioning of a variety of cells including those that line the renal tubules. It is our hypothesis that crystal deposition, i.e., formation and retention in the kidneys, is a result of impaired cellular function, which may be intrinsic and inherent or triggered by external stimuli and challenges. Cellular impairment or dysfunction affects the supersaturation, by influencing the excretion of participating ions such as calcium, oxalate and citrate and causing hypercalciuria, hyperoxaluria or hypocitraturia. The production and excretion of macromolecular promoters and inhibitors of crystallization is also dependent upon proper functioning of the renal epithelial cells. Insufficient or ineffective crystallization modulators such as osteopontin, Tamm-Horsfall protein, bikunin, etc. are most likely produced by the impaired cells.

Minimally Invasive Approaches to Upper Urinary Tract Urolithiasis

The surgical management of urolithiasis is an ever-changing discipline that presents unique challenges to the urologist. This article reviews the current minimally invasive treatment options for upper urinary tract urolithiasis. First it examines several factors that influence stone-free rates, including Hounsfield units of calculi, obesity, and lower pole factors. Surgical management of ureteral calculi is reviewed along with a discussion of stone management in high-risk patients including those who are pregnant. Surgical technique of shockwave lithotripsy, ureteroscopy, percutaneous nephrolithotomy, and laparoscopy is discussed in depth, with attention paid to possible variations in technique.