Ruslan Korets

Defining Early Morbidity of Radical Cystectomy for Patients with Bladder Cancer Using a Standardized Reporting Methodology

BACKGROUND Reporting methodology is highly variable and nonstandardized, yet surgical outcomes are utilized in clinical trial design and evaluation of healthcare provider performance. OBJECTIVE We sought to define the type, incidence, and severity of early postoperative morbidities following radical cystectomy (RC) using a standardized reporting methodology. DESIGN, SETTING, AND PARTICIPANTS Between 1995 and 2005, 1142 consecutive RCs were entered into a prospective complication database and retrospectively reviewed for accuracy. All patients underwent RC/urinary diversion by high-volume fellowship-trained urologic oncologists. MEASUREMENTS All complications within 90 d of surgery were analyzed and graded according to the Memorial Sloan-Kettering Cancer Center complication grading system. Complications were defined and stratified into 11 specific categories. Univariate and multivariate regression models were used to define predictors of complications. RESULTS AND LIMITATIONS Sixty-four percent (735/1142) of patients experienced a complication within 90 d of surgery. Among patients experiencing a complication, 67% experienced a complication during the operative hospital admission and 58% following discharge. Overall, the highest grade of complication was grade 0 in 36% (n=407), grade 1-2 in 51% (n=582), and grade 3-5 in 13% (n=153). Gastrointestinal complications were most common (29%), followed by infectious complications (25%) and wound-related complications (15%). The 30-d mortality rate was 1.5%. CONCLUSIONS Surgical morbidity following RC is significant and, when strict reporting guidelines are incorporated, higher than previously published. Accurate reporting of postoperative complications after RC is essential for counseling patients, combined modality treatment planning, clinical trial design, and assessment of surgical success.

NF-κB Regulates Androgen Receptor Expression and Prostate Cancer Growth

Prostate cancers that progress during androgen-deprivation therapy often overexpress the androgen receptor (AR) and depend on AR signaling for growth. In most cases, increased AR expression occurs without gene amplification and may be due to altered transcriptional regulation. The transcription factor nuclear factor (NF)-kappaB, which is implicated in tumorigenesis, functions as an important downstream substrate of mitogen-activated protein kinase, phosphatidylinositol 3-kinase, AKT, and protein kinase C and plays a role in other cancer-associated signaling pathways. NF-kappaB is an important determinant of prostate cancer clinical biology, and therefore we investigated its role in the regulation of AR expression. We found that NF-kappaB expression in prostate cancer cells significantly increased AR mRNA and protein levels, AR transactivation activity, serum prostate-specific antigen levels, and cell proliferation. NF-kappaB inhibitors decrease AR expression levels, prostate-specific antigen secretion, and proliferation of prostate cancer cells in vitro. Furthermore, inhibitors of NF-kappaB demonstrated anti-tumor activity in androgen deprivation-resistant prostate cancer xenografts. In addition, levels of both NF-kappaB and AR were strongly correlated in human prostate cancer. Our data suggest that NF-kappaB can regulate AR expression in prostate cancer and that NF-kappaB inhibitors may have therapeutic potential.

Predicting renal functional outcomes after surgery for renal cortical tumours: a multifactorial analysis

Study Type – Therapy (case series)
Level of Evidence 4

Expression of the circadian clock gene Period 1 in neuroendocrine cells: an investigation using mice with a Per1::GFP transgene.

The circadian clock located in the suprachiasmatic nuclei (SCN) of the hypothalamus regulates daily temporal organization in behaviour and neuroendocrine function. The molecular basis for circadian rhythm generation is an interacting transcriptional/translational feedback loop comprised of several ‘clock genes’ and their respective protein products. Clock genes are expressed not only in the SCN but also in numerous other locations throughout the brain, including regions rich in neuroendocrine cells. In order to investigate whether neuroendocrine cells function as autonomous oscillators, we used female transgenic mice in which an unstable, degradable jellyfish green fluorescent protein (GFP) gene is driven by a mouse Period 1 (Per1) gene promoter. Mice were injected (s.c.) with fluorogold (FG) in order to label neuroendocrine cells and brain sections were double‐labelled for either FG and Per1 mRNA (labelled by GFP immunostaining) or FG and PER1 protein using fluorescence immunocytochemistry. Mice were killed during either the day or night. Neuroendocrine cells contained Per1 mRNA and PER1 protein in several brain regions with the greatest proportion of double‐labelled cells occurring in the arcuate nucleus (Arc). The number of neuroendocrine cells labelled was not affected by the stage of the estrous cycle. Fewer FG‐labelled cells expressed Per1 message and protein during the night compared to the day. In the Arc, staining for tyrosine hydroxylase revealed that neuroendocrine cells expressing Per1 message and protein were dopaminergic. Together, these findings suggest that neuroendocrine cells contain the molecular machinery necessary to oscillate independently. It remains to be determined whether these cells actually function as autonomous oscillators or whether these rhythms are driven by signals from the SCN. These findings also indicate that the endocrine system represents an opportunity to study the interactions between central (SCN and neuroendocrine cells) and peripheral circadian (endocrine gland) oscillators.

Post-Percutaneous Nephrolithotomy Systemic Inflammatory Response: A Prospective Analysis of Preoperative Urine, Renal Pelvic Urine and Stone Cultures

PURPOSE Prior studies suggest that renal pelvic urine culture is a more accurate predictor of urosepsis. We prospectively determined the correlation between preoperative bladder urine cultures, intraoperative renal pelvis cultures and stone cultures in patients undergoing percutaneous nephrolithotomy. We also examined post-procedure risk factors for systemic inflammatory response syndrome. MATERIALS AND METHODS From February 2009 to February 2011 urine samples from the bladder and renal pelvis were collected from patients undergoing percutaneous nephrolithotomy. Extracted stones were also sent for culture analysis. Postoperatively patients were closely monitored for any signs of systemic inflammatory response syndrome. The concordance of urine and stone cultures across different sites was examined. Regression analysis was done to identify clinical variables associated with systemic inflammatory response syndrome. RESULTS A total of 204 percutaneous nephrolithotomies were done in 198 patients, of whom 20 (9.8%) had evidence of systemic inflammatory response syndrome postoperatively, including 6 (30%) requiring intensive care. The concordance among stone, renal pelvic and preoperative cultures was 64% to 75% with the highest concordance between renal pelvic urine and stone cultures. In a multivariate model multiple access tracts and a stone burden of 10 cm(2) or greater were significant predictors of systemic inflammatory response syndrome postoperatively. CONCLUSIONS Even appropriately treated preoperative urinary infections may not prevent infected urine at percutaneous nephrolithotomy. Renal pelvic urine and stone cultures may be the only way to identify the causative organism and direct antimicrobial therapy. We recommend collecting pelvic urine and stone cultures to identify the offending organism in patients at risk for sepsis, particularly those with a large stone burden requiring multiple access tracts.

Validating the Use of the Mimic dV-trainer for Robotic Surgery Skill Acquisition Among Urology Residents

OBJECTIVE To compare robotic surgery skill acquisition of residents trained with Mimic dVTrainer (MdVT) and da Vinci Surgical System (dVSS) console. No standardized curriculum currently exists for robotic surgical education. The MdVT is a compact hardware platform that closely reproduces the experience of the dVSS. METHODS Sixteen urology trainees were randomized into 3 groups. A baseline evaluation using dVSS was performed and consisted of 2 exercises requiring endowrist manipulation (EM), camera movement and clutching (CC), needle control (NC), and knot-tying (KT). Groups 1 and 2 completed a standardized training curriculum on MdVT and dVSS, respectively. Group 3 received no additional training. After completion of the training phase, all trainees completed a secondary evaluation on dVSS consisting of the same exercises performed during baseline evaluation. RESULTS There was no difference in baseline performance scores across the 3 groups. Although Group 3 showed no significant improvement in EM/CC domain (P = .15), Groups 1 and 2 had statistically significant improvement in EM/CC domain (P = .039 and P = .007, respectively). The difference in improvement between Groups 1 and group 2 was not statistically different (P = .21). Only Group 2 trainees showed significant improvement in the NC and KT domains during secondary evaluation (P = .02). CONCLUSION Curriculum-based training with MdVT or dVSS significantly improves robotic surgery aptitude. Similar improvements are seen for exercise domains shared between MdVT and dVSS groups. Follow-up studies are necessary to assess the efficacy of MdVT over a wider spectrum of domains.

Effect of Vitamin D Repletion on Urinary Calcium Excretion among Kidney Stone Formers

BACKGROUND AND OBJECTIVES Despite the important role of vitamin D in maintaining bone health, many clinicians are reluctant to treat vitamin D deficiency in kidney stone formers because of the theoretical risk of increasing urinary calcium excretion. This study examined the effect of vitamin D repletion on urinary calcium excretion among stone formers. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Participants (n=29) were recruited from urology clinics affiliated with New York Presbyterian Hospital. Enrollment criteria included a history of nephrolithiasis, urinary calcium excretion between 150 and 400 mg/d, and a serum 25-hydroxyvitamin D level <30 ng/ml. Participants were given oral ergocalciferol (50,000 IU/wk) for 8 weeks. Serum and 24-hour urine tests were repeated after 8 weeks. RESULTS Levels of 25-hydroxyvitamin D increased significantly after vitamin D repletion (17±6 and 35±10 ng/ml, P<0.001), but mean 24-hour urinary calcium excretion did not change (257±54 and 255±88 mg/d at baseline and follow-up, respectively, P=0.91). However, 11 participants had an increase in urinary calcium excretion ≥20 mg/d; these participants also had an increase in urine sodium excretion, likely reflecting dietary variability. No participant experienced adverse effects from vitamin D, including hypercalcemia. CONCLUSIONS Among stone formers with vitamin D deficiency, a limited course of vitamin D repletion does not seem to increase mean urinary calcium excretion, although a subset of individuals may have an increase. These data suggest that vitamin D therapy, if indicated, should not be withheld solely on the basis of stone disease, but 24-hour urinary calcium excretion should be monitored after repletion.

Partial penectomy for patients with squamous cell carcinoma of the penis: the Memorial Sloan-Kettering experience.

BackgroundTo present our institution’s experience with squamous cell carcinoma (SCC) of the penis, with analysis of oncologic efficacy and survival.MethodsBetween 1989 and 2005, we identified 32 consecutive patients (median age, 61 years) with SCC of the penis managed with partial penectomy. Clinicopathologic variables were examined, and overall and disease-specific survival were determined.ResultsPathologic stage of the primary tumor was pTis in 1 patient (3%), pT1 in 11 (34%), pT2 in 16 (50%), and pT3 in 4 (13%). Pathologic grade was well differentiated in 9 patients (28%), moderately differentiated in 20 (63%), and poorly differentiated in 2 (6%). Twenty-five patients (78%) underwent inguinal lymph node dissection, with 15 (60%) demonstrating nodal metastases. Twenty-two patients (69%) underwent pelvic lymph node dissection; 21 were negative for pelvic nodal metastases, and 1 had grossly positive nodes. One patient developed local recurrence. After a mean follow-up of 34 months, overall survival was 56%. Numbers of patients alive and disease-free were 9 and 11 in the low-stage and advanced-stage groups, and 8 and 12 in the well and moderately differentiated groups, respectively. Both patients with poorly differentiated disease died of disease within 12 months from presentation.ConclusionsPartial penectomy for SCC of the penis provides excellent local control, with low recurrence rate, and acceptable maintenance of urinary and sexual function. Outcomes are generally poor, however, for patients with regional metastases, even in moderately differentiated disease. Future studies are needed to identify a reliable method of predicting regional metastases.

Venous thromboembolism after major urologic oncology surgery: a focus on the incidence and timing of thromboembolic events after 27,455 operations.

OBJECTIVE To investigate the incidence and timing of venous thromboembolism (VTE) and identify risk factors for venous thromboembolism among patients undergoing major surgery for urologic malignancies. VTE events are stratified by occurrence in the inpatient vs outpatient settings. MATERIALS AND METHODS The National Surgical Quality Improvement Program database was queried using Current Procedural Terminology and International Statistical Classification of Diseases, Ninth Revision codes to identify patients undergoing major surgery for urologic malignancies between 2005 and 2012. The incidence of overall 30-day VTE, postdischarge VTE, and post-VTE death was calculated for each surgical procedure. Logistic regression analysis was used to identify risk factors for VTE, adjusting for covariates including age, race, gender, smoking status, medical comorbidities, performance of pelvic lymph node dissection, and operative time. RESULTS The study identified 27,455 patients who underwent an operation for malignancy--radical nephrectomy, partial nephrectomy, nephroureterectomy, radical prostatectomy, or radical cystectomy. The incidence and timing of VTE varied substantially across the procedures of interest. Overall, VTE occurred after radical cystectomy in 113 of 2065 of patients (5.5%), whereas only 19 of 2624 (0.7%) and 12 of 1690, respectively, of patients undergoing minimally invasive radical or partial nephrectomy procedures suffered a VTE event within 30-days of surgery. Among patients suffering a VTE after radical prostatectomy, 147 of 178 of venous thromboembolic events (82.6%) occurred after hospital discharge. CONCLUSION This study demonstrates the significant burden of VTE beyond the time of hospital discharge. Identification of high-risk patients should prompt consideration of extended-duration VTE prophylaxis in the outpatient setting.

Who Really Benefits From Nephron-sparing Surgery?

OBJECTIVE To analyze the influence of preoperative renal function on postoperative renal outcomes after radical nephrectomy (RN) and nephron-sparing surgery (NSS) for malignancy in patients stratified according to preoperative chronic kidney disease (CKD) stage and surgical extent (NSS vs RN). PATIENTS AND METHODS Retrospective review of patients undergoing renal surgery for localized renal masses stratified by surgical extent and preoperative CKD stage based on glomerular filtration rate (GFR) level: stage I (>90 mL/min/1.73 m(2)), stage II (60-89 mL/min/1.73 m(2)), and stage III (30-59 mL/min/1.73 m(2)). Survival analysis for significant renal impairment was based on freedom from the development of new-onset GFR <30 or <45 mL/min/1.73 m(2). RESULTS A total of 1306 patients were included in the analysis with preoperative CKD stage I (27.9%), II (52.1%), and III (20.1%); 41.3% and 58.7% underwent NSS and RN, respectively. NSS was associated with a lower annual rate of GFR decline in preoperative CKD stage-I (P = .028) and stage-II patients (P = .018), but not in CKD stage-III patients (P = .753). Overall, 5.0% and 15.0% developed new-onset GFR <30 mL/min/1.73 m(2) and <45 mL/min/1.73 m(2), respectively. There was no difference in the probability of developing significant renal impairment between NSS and RN in CKD stage-I or -III patients, whereas only in CKD stage-II patients was the surgical extent independently associated with development of significant renal impairment (RN: odds ratio, 9.0; P = .042 for GFR <30 mL/min/1.73 m(2) and odds ratio, 2.3; P = .003 for GFR <45 mL/min/1.73 m(2)). CONCLUSION Compared with RN, NSS is associated with a lower rate of GFR decline for preoperative CKD stage-I and -II patients, but only CKD stage-II patients demonstrated a decreased risk of developing significant renal impairment.