Julia B. Finkelstein

Validation of a frailty index in patients undergoing curative surgery for urologic malignancy and comparison with other risk stratification tools.

OBJECTIVE To retrospectively validate and compare a modified frailty index predicting adverse outcomes and other risk stratification tools among patients undergoing urologic oncological surgeries. MATERIALS AND METHODS The American College of Surgeons National Surgical Quality Improvement Program was queried from 2005 to 2013 to identify patients undergoing cystectomy, prostatectomy, nephrectomy, and nephroureterectomy. Using the Canadian Study of Health and Aging Frailty Index, 11 variables were matched to the database; 4 were also added because of their relevance in oncology patients. The incidence of mortality, Clavien-Dindo IV complications, and adverse events were assessed with patients grouped according to their modified frailty index score. RESULTS We identified 41,681 patients who were undergoing surgery for presumed urologic malignancy. Patients with a high frailty index score of >0.20 had a 3.70 odds of a Clavien-Dindo IV event (CI: 2.865-4.788, P<0.0005) and a 5.95 odds of 30-day mortality (CI: 3.72-9.51, P<0.0005) in comparison with nonfrail patients after adjusting for race, sex, age, smoking history, and procedure. Using C-statistics to compare the sensitivity and specificity of the predictive ability of different models per risk stratification tool and the Akaike information criteria to assess for the fit of the models with the data, the modified frailty index was comparable or superior to the Charlson comorbidity index but inferior to the American Society of Anesthesiologists Risk Class in predicting 30-day mortality or Clavien-Dindo IV events. When the modified frailty index was augmented with the American Society of Anesthesiologists Risk Class, the new index was superior in all aspects in comparison to other risk stratification tools. CONCLUSION Existing risk stratification tools may be improved by incorporating variables in our 15-point modified frailty index as well as other factors such as walking speed, exhaustion, and sarcopenia to fully assess frailty. This is relevant in diseases such as kidney and prostate cancer, where surveillance and other nonsurgical interventions exist as alternatives to a potentially complicated surgery. In these scenarios, our modified frailty index augmented by the American Society of Anesthesiologists Risk Class may help inform which patients have increased surgical complications that may outweigh the benefit of surgery although this index needs prospective validation.

Gene polymorphisms and prostate cancer: the evidence.

Prostate cancer is still the most frequent noncutaneous male malignancy and is the second most common cause of cancer death. Genetic factors have been extensively studied in different countries. In addition, numerous genome–wide association studies have been performed in developed countries. Genetic tests will be applied in the near future for diagnosis, therapeutic, and prognostic significance. Therefore, we reviewed the association of several important pathways and genes with critical functions in prostate cancer development or progression.

Benign Prostatic Hyperplasia: Current Clinical Practice

Benign prostatic hyperplasia (BPH) is the most common benign adenoma in men, affecting nearly all of them. BPH represents a clinically significant cause of bladder outflow obstruction in up to 40% of men. The growing frequency of diagnosis is due to increasing life expectancy and a trend toward seeking medical advice at earlier stages of the disease. The last decade has witnessed a significant shift in emphasis in the management of BPH, with medical therapies and, to a lesser extent, minimally invasive therapies becoming the predominant active therapy choices. The development of effective therapies such as alpha-adrenergic blockers and 5-alpha-reductase inhibitors and the possibility of their combined use represent the most significant advance in the treatment of BPH.

Prostate-specific Antigen Testing and Prostate Cancer Screening

Prostate specific antigen (PSA) screening is an integral part of current screening for prostate cancer. Together with digital rectal examinations, it is recommended annually by the American Cancer Society. PSA screening has resulted in a significant stage migration in the past decades. Different forms of PSA, including free PSA, volume adjusted, complexed, intact, or pro-PSA, are being used in the screening process. Other aspects of the screening process include age at diagnosis, survival, overdiagnosis, and overtreatment. Recent studies have cast doubt on whether PSA screening positively affects mortality and how the quality of life of patients may be affected by screening. Future considerations include the need for more longitudinal studies as well as further study of the PSA components that may become more relevant in the future.

Patterns of care for readmission after radical cystectomy in New York State and the effect of care fragmentation

OBJECTIVE To determine if readmission after radical cystectomy (RC) to the original hospital of the procedure (OrH) vs. readmission to a different hospital (DiffH) has an effect on outcomes. METHODS The New York Statewide Planning and Research Cooperative System database was queried for discharges between January 1, 2009 and November 31, 2012 after RC in New York State. Primary outcome was mortality within 30 and 90 days. Secondary outcomes included length of stay for readmission, rate of transfers/subsequent readmissions, hospital charges per readmission, and, if applicable, length of intensive care unit stays. Multivariate linear regression analyses were performed to adjust for confounding factors in predicting mortality. RESULTS During the study period, 2,338 patients were discharged from 100 New York State hospitals after RC. Overall rate of readmission was 28.5% and 39.7% within 30 and 90 days, respectively. Of all readmitted patients, 80.4% and 77.1% were first readmitted to OrH within 30 and 90 days, respectively. Patients readmitted to OrH were younger (P<0.0005) and had a lower All Patient Refined Severity of Illness (P = 0.004). Patients readmitted to DiffH had shorter length of stay (P<0.0005) and lower hospital charges per readmission (P<0.0005), but higher rates of transfers/subsequent readmissions (P = 0.007) and intensive care unit stays (P = 0.002) at 90 days. Patients initially readmitted to DiffH also had a higher rate of mortality (30d, 7.8% vs. 2.3%, P = 0.002; 90d, 5.2% vs. 2.5%, P = 0.05), but initial readmission status was not significant for mortality when controlling for other variables of interest. CONCLUSION Initial readmission to DiffH vs. OrH after RC was associated with higher rates of mortality, likely owing to underlying differences in the populations.

The short‐term use of erythropoetin‐stimulating agents: impact on the biochemical recurrence of prostate cancer

Study Type – Harm (case series)

Management and outcomes for children with pyloric stenosis stratified by hospital type.

BACKGROUND Access to health care has been a source of controversy and public attention in health policy. The issues of access to and utilization of the healthcare system by infants and children is less well documented. Moreover, the impact on outcomes of race, ethnicity, and economic status in infants is vaguely addressed. METHODS We performed a retrospective analysis of children who had undergone pyloromyotomy from July 31, 1998 to July 31, 2008 at our public hospital and university teaching hospital. Data abstracted included gestational age at delivery, birth weight, gender, race, insurance status, age at presentation, symptom duration, preoperative ultrasound (US), operative date, laboratory evaluations, as well as preoperative, postoperative, and total length of stay (LOS). RESULTS The mean total preoperative LOS was twice as long at our public hospital than our private hospital (1.78 d versus 0.85 d, P=0.003). Similarly, the mean total length of stay was 0.87 d longer at our public hospital (3.87 d versus 3 d), which trended toward significance (P=0.06). Significantly, 72% (27/33) patients at the private hospital had their US either as an out-patient or on the day of admission, while only 58% (28/48) had an US performed as expeditiously at the public hospital (P=0.03, chi(2) analysis). CONCLUSIONS Care at our public hospital leads to delayed diagnosis and treatment, resulting in longer preoperative and total LOS in infants with pyloric stenosis, most likely related to the timing of the preoperative US. Efforts should be made to encourage patients to use the outpatient clinic facilities for their ill infants, or for physicians at public hospitals to expedite the US process once the diagnosis of pyloric stenosis is entertained.

Renal functional outcomes after surgery for renal cortical tumors

Historically, radical nephrectomy represented the gold standard for the treatment of small (≤ 4cm) as well as larger renal masses. Recently, for small renal masses, the risk of ensuing chronic kidney disease and end stage renal disease has largely favored nephron-sparing surgical techniques, mainly partial nephrectomy. In this review, we surveyed the literature on renal functional outcomes after partial nephrectomy for renal tumors. The largest randomized control trial comparing radical and partial nephrectomy failed to show a survival benefit for partial nephrectomy. With regards to overall survival, surgically induced chronic kidney disease (GFR < 60 ml/min/ 1.73m2) caused by nephrectomy might not be as deleterious as medically induced chronic kidney disease. In evaluating patients who underwent donor nephrectomy, transplant literature further validates that surgically induced reductions in GFR may not affect patient survival, unlike medically induced GFR declines. Yet, because patients who present with a renal mass tend to be elderly with multiple comorbidities, many develop a mixed picture of medically, and surgically-induced renal disease after extirpative renal surgery. In this population, we believe that nephron sparing surgery optimizes oncological control while protecting renal function.

MP42-04 CHARACTERIZING DEVELOPMENT OF THE HUMAN LOWER URINARY TRACT: ANATOMIC FEATURES AND MOLECULAR EXPRESSION OF THE URETERIC BUD AND CLOACA

INTRODUCTION AND OBJECTIVES: Nerve growth factor (NGF) has been implicated as an important mediator to induce C-fiber bladder afferent hyperexcitability, which contributes to the emergence of neurogenic detrusor overactivity (NDO) following spinal cord injury (SCI). In this study, we examined whether NGF neutralization using anti-NGF antibody normalizes the SCI-induced changes in electrophysiological properties of capsaicin-sensitive C-fiber bladder afferent neurons in the mouse model. METHODS: In female C57BL/6 mice, the spinal cord was transected at the Th8/9 level. Two weeks later, an osmotic pump was placed subcutaneously to administer anti-NGF antibody at 10 mg/kg/h for 2 weeks. Bladder afferent neurons were labeled with axonal transport of Fast Blue (FB), a fluorescent retrograde tracer, injected into the bladder wall 3 weeks after SCI. Four weeks after SCI, freshly dissociated L6-S1 dorsal root ganglion neurons were prepared. Whole cell patch clamp recordings were then performed in FB-labeled bladder afferent neurons, and the data were compared between SCI and spinal intact (SI) mice. After recording action potentials (AP) or voltage-gated K (Kv) currents, the sensitivity of each neuron to capsaicin was evaluated. RESULTS: In capsaicin-sensitive bladder afferent neurons, the resting membrane potentials and the peak and duration of AP did not changed by SCI. On the other hand, the threshold for eliciting AP was significantly reduced in SCI vs. SI mice. Also, SCI increased the number of AP during 800 ms membrane depolarization. These SCI induced changes were reversed by NGF neutralization. SCI induced significant increases in the diameter and cell input capacitance of capsaicin-sensitive bladder afferent neurons, which were not reversed by NGF neutralization. Densities of slow decaying KA and sustained KDR currents evoked by depolarization to 0 mV were significantly reduced by SCI. NGF neutralization reversed the SCI-induced reduction in the KA current density. CONCLUSIONS: In SCI mice, NGF plays an important role in hyperexcitability of capsaicin sensitive C-fiber bladder afferent neurons due to KA current reduction. Thus, NGF-targeting therapies could be effective for treatment of afferent hyperexcitability and NDO in SCI.

MP66-19 THE DECLINING RATE OF PEDIATRIC VARICOCELECTOMY IN NEW YORK STATE

INTRODUCTION AND OBJECTIVES: Bilateral Vanishing Testis Syndrome is one of the most challenging problems of pediatric and adolescent urology. There are at least two major problems for patients with congenital or acquired anorchia: Long-life androgen replacement therapy and possible hepatic cancer occurrence as well as fertility issue. The purpose of present study was to describe a method to produce human sized decellularized testis scaffold as a primitive step for testis tissue engineering in such complex situation. METHODS: A total of 32 sheep testes were classified in 8 groups of 4. Seven decellularization protocols were proposed which were tested on groups 1-7, respectively and group 8 was left intact as the control group. The protocols consisted of 0.5%, 1%, 2% solution of sodium dodecyl sulfate (SDS), Trypsin-EDTA 0.5%, 1%, Triton X-100 1% and 2%, respectively. Then, using the best protocol obtained in phase I, the optimal timing was evaluated; ovine testes were decellularized by arterial perfusion and specimen were collected for evaluation at 4-6-8-10-12 hours after initiation of the procedure, respectively. To evaluate the efficacy of the protocol, histological examinations, scanning electron microscopy (SEM), magnetic resonance imaging (MRI) biochemical assays and evaluation of mechanical properties were performed. The patency of vascular network of the decellularized scaffold was examined by angiography. The cytotoxicity analyses of samples was performed by tetrazolium salt MTT (3-[4,5dimethylthiazol2-yl]-2,5-diphenyltetrazolium bromide) assay. RESULTS: Histological exams depict that treating the tissues with SDS 1% for 6-8 hours was found to be the best protocol for cell removal and preserving the extracellular matrix (ECM) components. The microstructure, ultrastructure and vascular integrity of the decellularized testis scaffold were well-preserved and confirmed by scaffold angiography, SEM and MRI. Moreover, MTT assay showed that the decellularized testis was not cytotoxic to cells and it is ready for recellularization. CONCLUSIONS: The SDS 1% with 6-8 hours perfusion based protocol is the best, effective, minimally invasive technique for creation of whole testis bioscaffold with well-preserved extra-cellular matrix structure and vascular network integrity. To the best of our knowledge the whole large size testis decellularization by this novel protocol has not been reported previously. This preliminary step may pave the road for slowing these problems in future.