Upper tract urothelial carcinoma with Oligometastasis to the right ventricle, surgical considerations, and management.

Right ventricular (RV) metastasis from an upper tract urothelial carcinoma without inferior vena cava or right atrial involvement is an extremely rare event which highlights the heterogeneity of this disease process. We report a case of a 43-year-old man presenting for long-standing hematuria and left flank pain. Computed tomography revealed a left renal mass with para-aortic lymphadenopathy, in addition to a potential mass in the RV. The mass involving the RV was confirmed on subsequent cardiac evaluation with magnetic resonance imaging (MRI) and echocardiography. After discussion in a multidisciplinary tumor board, the patient underwent a left nephrectomy, regional lymphadenectomy, and excision of metastatic RV tumor with bovine patch reconstruction. Final pathology reported invasive urothelial carcinoma in the left kidney with involvement of regional para-aortic lymph nodes and metastatic tumor in the RV (T4N3M1, AJCC 8th edition). The patient did well postoperatively and completed adjuvant Cisplatin-Gemcitabine systemic chemotherapy. This is an important addition to the literature as it highlights the aggressive and heterogeneous nature of urothelial carcinoma and the utility of cardiac MRI in surgical planning.

Office Cystoscopy Urinary Tract Infection Rate and Cost before and after Implementing New Handling and Storage Practices.

INTRODUCTION: Based on 2010 American Urological Association recommendations our practice transitioned from sterile to high level disinfection flexible cystoscope reprocessing and from sterile to clean handling practices. We examined symptomatic urinary tract infection rate and cost before and after policy implementation. METHODS: We retrospectively reviewed 30-day outcomes following 1,888 simple cystoscopy encounters that occurred from 2007 to 2010 (sterile, 905) and 2012 to 2015 (high level disinfection, 983) at the Malcom Randall Veterans Affairs Medical Center. We excluded veterans who had recent instrumentation, active or recent urinary tract infection, performed intermittent catheterization, or had complicated cystoscopy (dilation, biopsy etc). Patient/procedural factors and cost were collected and compared between groups. RESULTS: Both cohorts had similar age (mean 68 years), race (Caucasian, 82%), comorbidities (cancer history, 62%; diabetes mellitus, 36%; tobacco use, 24.5%), and cystoscopy procedural indications (cancer surveillance, 50%; hematuria, 34%). Urological complication rate was low between groups (1.43%) with no significant difference in symptomatic urinary tract infection events (0.99% sterile vs 0.51% high level disinfection, p=0.29) or unplanned clinic/emergency department visits (0.66% sterile vs 0.71% high level disinfection, p=0.91). Roughly 95% of the cohorts were given prophylactic antibiotics, most commonly fluoroquinolones (91%). High level disinfection was $82 cheaper per procedure than sterile with most cost disparity stemming from reprocessing. Total savings for our facility by switching to high level disinfection was more than $100,000 annually. CONCLUSIONS: In an older, morbid veteran population receiving centralized care and prophylactic antibiotics we found no difference in symptomatic urinary tract infection or unplanned visits between sterile or high level disinfection techniques. However, high level disinfection was associated with a sizable cost savings, improved clinic workflow, and reduced use of personal protective equipment.

The Effect of Calcium and Vitamin B6 Supplementation on Oxalate Excretion in a Rodent Gastric Bypass Model of Enteric Hyperoxaluria.

OBJECTIVE: To test the effect of calcium and vitamin B6 therapies on urinary oxalate excretion in a rodent model of enteric hyperoxaluria after Roux-en Y gastric bypass (RYGB) surgery. METHODS: Obese male Sprague-Dawley rats underwent sham (n = 7) or RYGB (n = 10). Animals were maintained on low oxalate (1.5%) and fat (10%; LOF), normal calcium (0.6 %) diet for 8 weeks and then completed a 2-phase crossover metabolic study. In the first 2-week phase, animals were fed a Low oxalate and fat (LOF), high calcium (2.4%; HC) diet. After a 2-week washout, rats were fed a LOF/normal calcium diet highly enriched with vitamin B6. Urine was collected before and after each intervention. Plasma pyridoxal 5'-phosphate (PLP) and metabolites were measured baseline and 11 weeks after sham or RYGB. RESULTS: Compared to baseline, sham animals on LOF/HC diet doubled their urinary calcium excretion but not oxalate. RYGB animals on LOF/HC diet decreased urinary oxalate excretion 28% (P = .001) without a significant rise in urinary calcium. Vitamin B6 supplementation decreased RYGB urinary oxalate by approximately 15% (P = .06), and serum PLP explained 63% of urinary oxalate variability. CONCLUSION: Based on the findings in this model, calcium supplementation appears to be a reasonable therapy to decrease urinary oxalate in RYGB patients who maintain a low fat and oxalate diet. Serum PLP had a fair correlation to urinary oxalate excretion and may be a useful screening tool in hyperoxaluric RYGB patients. Further experimental human studies after RYGB are necessary to determine whether these commonly employed supplements truly provide a benefit in enteric hyperoxaluria.

Kidney Stones After Bariatric Surgery: Risk Assessment and Mitigation.

Obesity is rampant across the spectrum of age, gender, and race in the Unites States. Paralleling this epidemic, kidney stone prevalence is also rising, affecting nearly 1 in 11 individuals. Bariatric surgical procedures, such as Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), are the most effective weight loss options for morbidly obese or severely obese individuals with comorbidities. A number of studies have linked kidney stone development to bariatric surgical history, particularly RYGB, which portends up to a threefold increase in calcium oxalate stone risk compared with age-matched, obese controls. Stone development after malabsorptive (RYGB) and restrictive (SG) bariatric procedures are driven primarily by alterations in 24-h urine profiles, such as increased urinary oxalate, decreased urine volume, and reduced urinary citrate levels-all of which have been linked to increased kidney stone risk. What clinical recommendations, if any, can be given to reduce kidney stone risk in bariatric kidney stone patients? This review provides not only updated stone incidence and 24-h urine data in this population, but also reassurance-the metabolic alterations that result from bariatric surgery can be successfully mitigated by increased provider awareness, patient education, and a combination of dietary and pharmacological adjustments.

Intracardial embryonic delivery of developmental modifiers in utero.

Our knowledge of organ ontogeny is largely based on loss-of-function (knockout) or gain-of-function (transgenesis) approaches. However, developmental modulators such as proteins, mRNAs, microRNAs(miRNAs), small interfering RNAs, and other small molecules may complement the above DNA-modifying technologies in a much more direct way. Unfortunately, their use is often limited by the ability of these compounds to cross the placenta and reach physiologically relevant concentrations when administered systemically to the mother. The design of safe and effective techniques to deliver these compounds into the embryo is therefore an area of great scientific potential. In this article we report a new method for introducing developmental modulators into murine embryos by means of direct injection into the heart. Unlike other reported methods that require surgical exposure of the uterus, our percutaneous ultrasound-guided approach allows for the intracardial injection of mouse embryos as early as embryonic day 10.5 (e10.5) and throughout gestation in a minimally invasive manner that largely preserves embryo viability. This system offers a critical advantage over in vitro settings because the effects of any given treatment can be observed without disturbing the native environment of the developing organ. Procedures are described for the delivery and detection of transducible proteins as well as morpholinos designed to block the expression of specific miRNAs within the living embryo.

TAT-mediated transduction of MafA protein in utero results in enhanced pancreatic insulin expression and changes in islet morphology.

Alongside Pdx1 and Beta2/NeuroD, the transcription factor MafA has been shown to be instrumental in the maintenance of the beta cell phenotype. Indeed, a combination of MafA, Pdx1 and Ngn3 (an upstream regulator of Beta2/NeuroD) was recently reported to lead to the effective reprogramming of acinar cells into insulin-producing beta cells. These experiments set the stage for the development of new strategies to address the impairment of glycemic control in diabetic patients. However, the clinical applicability of reprogramming in this context is deemed to be poor due to the need to use viral vehicles for the delivery of the above factors. Here we describe a recombinant transducible version of the MafA protein (TAT-MafA) that penetrates across cell membranes with an efficiency of 100% and binds to the insulin promoter in vitro. When injected in utero into living mouse embryos, TAT-MafA significantly up-regulates target genes and induces enhanced insulin production as well as cytoarchitectural changes consistent with faster islet maturation. As the latest addition to our armamentarium of transducible proteins (which already includes Pdx1 and Ngn3), the purification and characterization of a functional TAT-MafA protein opens the door to prospective therapeutic uses that circumvent the use of viral delivery. To our knowledge, this is also the first report on the use of protein transduction in utero.