Impact of a Mediterranean diet on prevention and management of urologic diseases.

Compared to a Western diet, the Mediterranean diet moves away from red meat and processed foods. Universally regarded as a healthier dietary alternative, the Mediterranean diet has garnered scientific endorsement for its ability to confer an array of compelling benefits. These health benefits encompass not only a lowered incidence of Type 2 diabetes with a reduction in obesity, but also a robust protective effect on cardiovascular health. Extensive literature exists to corroborate these health benefits; however, the impact of a Mediterranean diet on urologic diseases, specifically sexual dysfunction, lower urinary tract symptoms, stone disease, and urologic cancers are not well studied. Understanding how dietary habits may impact these urologic conditions can contribute to improved prevention and treatment strategies.A total of 955 papers from PubMed and Embase were systematically reviewed and screened. After exclusion of disqualified and duplicated studies, 58 studies consisting of randomized controlled trials, cohort studies, cross sectional studies, reviews and other meta-analyses were included in this review. 11 primary studies were related to the impact of a Mediterranean diet on sexual dysfunction, 9 primary studies regarding urinary symptoms, 8 primary studies regarding stone disease, and 9 primary studies regarding urologic cancers. All primary studies included were considered of good quality based on a New-Castle Ottawa scale. The results demonstrate a Mediterranean diet as an effective means to prevent as well as improve erectile dysfunction, nephrolithiasis, lower urinary tract symptoms, and urinary incontinence. The review highlights the need for additional research to study the impact of diet on urologic cancers and other urologic conditions such as premature ejaculation, loss of libido, female sexual dysfunction, and overactive bladder.

Endophytic upper tract urothelial carcinoma in a solitary kidney treated by cryotherapy: an unorthodox case for successful management.

BACKGROUND: Nephroureterectomy remains the gold standard treatment for upper tract urothelial carcinoma (UTUC). Considering the high risk of developing renal function impairment after surgery, the rationale for nephron sparing approaches in treatment of UTUC has been raised. In this case, renal cryoablation was able to achieve successful oncologic control while preserving renal function during 5 years of follow up without intraoperative or post operative complications. CASE PRESENTATION: A 79 year old male presents after three months of macroscopic hematuria. Imaging revealed a 3.6 × 3.1 × 2.7 cm endophytic mass in the interpolar region of the left kidney and an atrophic right kidney. After weighing the lesion's location with the patient's of complex medical history, he was counselled to undergo a minimally invasive percutaneous cryoablation as treatment for his solitary renal mass. A diagnostic dilemma was encountered as imaging suggested a diagnosis of renal cell carcinoma. However, the pre-ablation biopsy established an alternative diagnosis, revealing UTUC. Percutaneous cryoablation became an unorthodox treatment modality for the endophytic component of his UTUC followed by retrograde ureteroscopic laser fulguration. The patient was followed in 3 months, 6 months, then annually with cross sectional imaging by MRI, cystoscopy, urine cytology and renal function testing. After five years of follow-up, the patient did not encountered recurrence of UTUC or deterioration in renal function, thereby maintaining a stable eGFR. CONCLUSION: Although evidence for nephron-sparing modalities for UTUC is mounting in recent literature, limited data still exists on cryotherapy as a line of treatment for urothelial carcinoma. We report successful management of a low-grade UTUC using cryoablation with the crucial aid of an initial renal biopsy and long-term follow-up. Our results provide insight into the role of cryoablation as a nephron-sparing approach for UTUC.

Pathological characteristics and prognostic indicators of different histopathological types of urinary bladder cancer following radical cystectomy in a large single-center Egyptian cohort.

OBJECTIVE: To evaluate differences in pathological features and prognostics across four bladder cancer histopathological types: urothelial carcinoma (UC), urothelial carcinoma with variant histology (UCV), squamous cell carcinoma (SCC) and adenocarcinoma (ADC), utilizing a large cohort of radical cystectomy (RC) patients. METHODS: A retrospective analysis of patients who underwent RC at a single institution in Egypt between 1997 and 2004 was performed. Kaplan-Meier and multivariable analyses were performed to evaluate the prognostic significance of pathological features including tumor stage, grade, lymphovascular invasion (LVI), and lymph node (LN) involvement in the different subtypes on disease-free survival (DFS). RESULTS: 1238 patients (975 male, 263 female) were included, of whom 577 (47%) had UC, 174 (14%) UCV, 398 (32%) SCC, and 89 (7%) ADC. Median age was 54 (20-87) years and median follow-up was 40 months (0-110). There were significant differences in stage, grade, LVI, LN involvement, and presence of schistosomiasis across the subtypes (all p < 0.05). The prognostic significance of LVI was more evident in SCC (HR 2.14, p = 0.003) and ADC (HR 2.17, p = 0.044) than in UC (HR 1.66, p = 0.008). LN involvement was the strongest prognostic factor in UCV (HR 2.14, p = 0.012). CONCLUSIONS: There are significant differences in clinicopathological features and their prognostic impact across bladder cancer subtypes. The prognostic significance of LVI is more evident in SCC and ADC, while LN involvement is more prognostic in UCV. Determining independent predictors in individual subtypes can guide multimodal treatment selection and clinical trial design.

Prognostic value of tissue-based biomarker signature in clear cell renal cell carcinoma.

OBJECTIVE: To improve risk stratification for recurrence prognostication in patients with localised clear cell renal cell carcinoma (ccRCC). PATIENTS AND METHODS: In all, 367 patients with non-metastatic ccRCC were included. The cohort was divided into a training and validation set. Using tissue microarrays, immunostaining was performed for 24 biomarkers representative of key pathways in ccRCC. Using Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression, we identified several markers that were used to construct a risk classifier for risk of disease recurrence. RESULTS: The median (interquartile range) follow-up was 63.5 (24.0-85.3) months. Five out of 24 markers were selected by LASSO Cox regression for the risk classifier: N-cadherin, E-cadherin, Ki67, cyclin D1 and phosphorylated eukaryotic initiation factor 4E binding protein-1 (p-4EBP1). Patients were classified as either low, intermediate or high risk of disease recurrence by tertiles of risk score. The 5-year recurrence-free survival (RFS) was 93.8%, 87.7% and 70% for patients with low-, intermediate- and high-risk scores, respectively (P < 0.001). Patients with a high marker score had worse RFS on multivariate analysis adjusted for age, gender, race and the Mayo Clinic Stage, Size, Grade, and Necrosis (SSIGN) score (hazard ratio 3.66, 95% confidence interval 1.58-8.49, P = 0.003 for high vs low marker score in the overall cohort). The five-marker classifier increased the concordance index of the clinical model in both the training and validation sets. CONCLUSION: We developed a five-marker-based prognostic tool that can effectively classify patients with ccRCC according to risk of disease recurrence after surgery. This tool, if prospectively validated, could provide individualised risk estimation for patients with ccRCC.

Multi-disciplinary surgical approach to the management of patients with renal cell carcinoma with venous tumor thrombus: 15 year experience and lessons learned.

BACKGROUND: The management of patients with renal cell carcinoma (RCC) with venous tumor thrombus (VTT) is challenging. We report our 15 year experience in the management of patients with RCC with VTT utilizing a multidisciplinary team approach, highlighting improved total and specifically Clavien III-V complication rates. METHODS: We reviewed the records of 146 consecutive patients who underwent radical nephrectomy with venous thrombectomy between 1998 and 2012. Data on patient history, staging, surgical techniques, morbidity, and survival were analyzed. Additionally, complication rates between two surgical eras, 1998-2006 and 2006-2012, were assessed. RESULTS: The study included 146 patients, 97 males (66 %), and a median age of 61 years (range, 24-83). Overall complications rate was 53 %, high grade complications (Clavien III -V) occurred in 10 % of patients. Most importantly, there was a lower incidence of overall and high grade complications (45 % and 8 %, respectively) in the last 6 years compared to the earlier surgeries included in the study (67 % and 13 % respectively) [p = .008 and .03, respectively). 30 day postoperative mortality was 2.7 %. 5 year overall survival (5Y- OS) and 5 year cancer specific survival (5Y- CSS) were 51 % and 40 %, respectively. Metastasis was the only independent predictor factor for CSS (HR 3.8, CI 1.9-7.6 and p < .001) and OS (HR 2.6, CI 1.5-4.7 and p = .001) in all patients. CONCLUSIONS: Our data suggest that patients with RCC and VTT can be treated safely utilizing a multidisciplinary team approach leading to a decrease in complication rates.

Utility of biomarkers in the prediction of oncologic outcome after radical cystectomy for squamous cell carcinoma.

PURPOSE: We evaluated the association of multiple biomarkers with clinical outcomes in patients treated with radical cystectomy for squamous cell carcinoma of the bladder to identify the best prognostic panel of markers. MATERIALS AND METHODS: Immunohistochemistry for 14 biomarkers was performed on tissue microarray sections of 151 radical cystectomy specimens showing squamous cell carcinoma. Biomarker alterations, pathological features and oncologic outcomes were evaluated. The panel of biomarkers that best predicted the oncologic outcome was determined. Outcomes were stratified based on a prognostic score according to the number of altered biomarkers. The accuracy of oncologic outcome prediction was evaluated by ROC curves. RESULTS: The study included 151 patients. Pathological stage was T2 in 50%, T3 in 38%, T1 in 6% and T4 in 6% of patients. Median followup was 63.2 months. The best prognostic panel of markers included COX-2, FGF-2, p53, Bax and EGFR. On multivariate Cox regression analysis a prognostic score based on marker alterations was an independent predictor of intermediate and high risk of disease recurrence (HR 3.2, p = 0.008 and HR 15.5, p ≤ 0.001) and bladder cancer specific mortality (HR 5.2, p = 0.009 and HR 19.4, p ≤ 0.001, respectively). A multivariate prognostic model incorporating the prognostic score demonstrated significantly better performance to predict the outcome compared to clinicopathological parameters only (0.78 vs 0.64). CONCLUSIONS: Biomarkers have significant potential to predict the outcome of radical cystectomy for squamous cell carcinoma. An increased number of altered markers may identify patients at high risk who might benefit from multimodal treatment approaches.

Redefining the Autonomic Nerve Distribution of the Bladder Using 3-Dimensional Image Reconstruction.

PURPOSE: We sought to create a 3-dimensional reconstruction of the autonomic nervous tissue innervating the bladder using male and female cadaver histopathology. MATERIALS AND METHODS: We obtained bladder tissue from a male and a female cadaver. Axial cross sections of the bladder were generated at 3 to 5 mm intervals and stained with S100 protein. We recorded the distance between autonomic nerves and bladder mucosa. We manually demarcated nerve tracings using ImageScope software (Aperio, Vista, California), which we imported into Blender™ graphics software to generate 3-dimensional reconstructions of autonomic nerve anatomy. RESULTS: Mean nerve density ranged from 0.099 to 0.602 and 0.012 to 0.383 nerves per mm2 in female and male slides, respectively. The highest concentrations of autonomic innervation were located in the posterior aspect of the bladder neck in the female specimen and in the posterior region of the prostatic urethra in the male specimen. Nerve density at all levels of the proximal urethra and bladder neck was significantly higher in posterior vs anterior regions in female specimens (0.957 vs 0.169 nerves per mm2, p<0.001) and male specimens (0.509 vs 0.206 nerves per mm2, p=0.04). CONCLUSIONS: Novel 3-dimensional reconstruction of the bladder is feasible and may help redefine our understanding of human bladder innervation. Autonomic innervation of the bladder is highly focused in the posterior aspect of the proximal urethra and bladder neck in male and female bladders.

Applications of three-dimensional printing technology in urological practice.

A rapid expansion in the medical applications of three-dimensional (3D)-printing technology has been seen in recent years. This technology is capable of manufacturing low-cost and customisable surgical devices, 3D models for use in preoperative planning and surgical education, and fabricated biomaterials. While several studies have suggested 3D printers may be a useful and cost-effective tool in urological practice, few studies are available that clearly demonstrate the clinical benefit of 3D-printed materials. Nevertheless, 3D-printing technology continues to advance rapidly and promises to play an increasingly larger role in the field of urology. Herein, we review the current urological applications of 3D printing and discuss the potential impact of 3D-printing technology on the future of urological practice.

TALL score for prediction of oncological outcomes after radical nephroureterectomy for high-grade upper tract urothelial carcinoma.

PURPOSE: We created a prognostic tool for the prediction of oncologic outcomes after radical nephroureterectomy (RNU) for high-grade non-metastatic upper tract urothelial carcinoma (UTUC). METHODS: UTUC collaboration was utilized to include 586 patients who underwent RNU for non-metastatic high-grade UTUC. Survival outcomes were compared according to a score defined based on the sum of the independent prognostic variables. RESULTS: The study included 382 males with a median age 70 years (range 28-97). Independent prognostic factors included: T (t stage), A (architecture), LVI (lympho-vascular invasion) and L (lymphadenectomy). TALL score (1-7) was the sum of T (≤T1 = 1, T2 = 2, T3 = 3 and T4 = 4), A (papillary = 0 and sessile = 1), LVI (absent = 0 and present = 1) and L (lymphadenectomy = 0 and no lymphadenectomy = 1). Five-year disease-free survival (DFS) and cancer-specific survival (CSS) were stratified into four risk categories according to the TALL score: low (TALL 0-2; 86 % DFS and 90 % CSS), intermediate (TALL = 3; 71 % DFS and 75 % CSS), high (TALL = 4; 57 % DFS and 58 % CSS) and very high risk (TALL ≥ 5; 34 % DFS and 38 % CSS) using Kaplan-Meier survival analyses. TALL score was externally validated in a single-center cohort of 85 UTUC patients. CONCLUSIONS: We developed a multivariable prognostic tool for the prediction of oncological outcomes after RNU for high-grade UTUC. The score can be used for patient counseling, selection for adjuvant systemic therapies and design of clinical trials.

Prospective analysis of Ki-67 as an independent predictor of oncologic outcomes in patients with high grade upper tract urothelial carcinoma.

PURPOSE: We determined the association of the proliferation marker Ki-67 with pathological parameters and oncologic outcomes in patients with high grade upper tract urothelial carcinoma. MATERIALS AND METHODS: Immunohistochemical staining for Ki-67 was done prospectively in 101 consecutive patients undergoing radical nephroureterectomy/ureterectomy for high grade upper tract urothelial carcinoma. Data were compared based on Ki-67 status (normal vs over expressed). Survival was assessed by the Kaplan-Meier method. Cox regression analysis was done to identify independent predictors of time dependent outcomes. RESULTS: Median patient age was 70.0 years and median followup was 22.0 months (range 1 to 77). Overall, 30.2% of the population experienced recurrence and 24.8% died of upper tract urothelial carcinoma. Organ confined disease (T2 or less and lymph node negative), lymphovascular invasion and sessile architecture were present in 56.3%, 33.3% and 20.8% of patients, respectively. Ki-67 was over expressed in 73.3% of patients and associated with adverse pathological features. Patients with over expressed Ki-67 had significantly worse recurrence-free survival (43.2 vs 69.0 months, p = 0.006) and cancer specific survival (48.9 vs 68.9 months, p = 0.031) than patients with normal Ki-67. Patients with nonmetastatic disease similarly had worse recurrence-free survival (40.7 vs 71.8 months, p = 0.003) and cancer specific survival (41 months vs not attained, p = 0.008) for over expressed vs normal Ki-67. After adjusting for the effects of organ vs nonorgan confined disease Ki-67 over expression was an independent predictor of recurrence-free survival in the total cohort (HR 4.3, p = 0.05) and in patients with nonmetastatic disease (HR 8.5, p = 0.038). CONCLUSIONS: Ki-67 over expression was associated with adverse pathological features in cases of upper tract urothelial carcinoma. It was also an independent predictor of recurrence-free survival in patients with high grade upper tract urothelial carcinoma.

Prospective comparison of molecular signatures in urothelial cancer of the bladder and the upper urinary tract--is there evidence for discordant biology?

PURPOSE: Upper tract urothelial carcinoma is rare and less well studied than bladder cancer. It remains questionable if findings in bladder cancer can safely be extrapolated to upper tract urothelial carcinoma. We prospectively evaluate molecular profiles of upper tract urothelial carcinoma and bladder cancer using a cell cycle biomarker panel. MATERIALS AND METHODS: Immunohistochemical staining for p21, p27, p53, cyclin E and Ki-67 was prospectively performed for 96 patients with upper tract urothelial carcinoma and 159 patients with bladder cancer with nonmetastatic high grade urothelial carcinoma treated with extirpative surgery. Data were compared between the groups according to pathological stage. Primary outcome was assessment of differences in marker expression. Secondary outcome was difference in survival according to marker status. RESULTS: During a median followup of 22.0 months 31.2% of patients with upper tract urothelial carcinoma and 28.3% of patients with bladder cancer had disease recurrence, and 20.8% and 27.7% died of upper tract urothelial carcinoma and bladder cancer, respectively. The number of altered markers was not significantly different between the study groups. Overall 34 patients (35.4%) with upper tract urothelial carcinoma and 62 (39.0%) with bladder cancer had an unfavorable marker score (more than 2 markers altered). There were no significant differences between upper tract urothelial carcinoma and bladder cancer in the alteration status of markers, the number of altered markers and biomarker score when substratified by pathological stage. There were no significant differences in survival outcomes between patients with upper tract urothelial carcinoma and those with bladder cancer according to the number of altered markers and biomarker score. CONCLUSIONS: Our results demonstrate the molecular similarity of upper tract urothelial carcinoma and bladder cancer in terms of cell cycle and proliferative tissue markers. These findings have important implications and support the further extrapolation of treatment paradigms established in bladder cancer to upper tract urothelial carcinoma.

Ki67 is an independent predictor of oncological outcomes in patients with localized clear-cell renal cell carcinoma.

OBJECTIVE: To validate the impact of Ki67 expression on oncological outcomes of patients treated for clinically localized clear-cell renal cell carcinoma (ccRCC). PATIENTS AND METHODS: Immunohistochemistry for Ki67 was performed on tissue microarray constructs of patients treated with radical or partial nephrectomy for clinically localized (M0) ccRCC and Ki67 expression >10% was considered abnormal. Clinical and pathological data elements were entered into an institutional review board-approved database. The Kaplan-Meier method and Cox regression models were used to analyse disease-free survival (DFS) and cancer-specific survival (CSS) probabilities. RESULTS: Of 401 patients, 59.6% were males. The median (range) age was 58 (17-85) years, follow-up was 22 (0-150) months and time to death was 27 (0-150) months. A total of 20.2% of patients had advanced stage (pT3-T4) and 31% had advanced grade (3-4) disease. Abnormal expression of Ki67 was seen in 6.5% of our cohort and was associated with adverse pathological features (P < 0.05). Patients with high expression of Ki67 were found to have 5-year DFS and CSS rates of 67 and 84%, respectively, vs 87 and 95%, respectively, in those with normal expression (P < 0.001 and P < 0.05, respectively). In multivariable analyses, adjusting for stage and grade, abnormal Ki67 expression was an independent predictor of DFS (hazard ratio [HR] 3.77, P = 0.011, 95% confidence interval [CI] 1.35-10.52), but not of CSS (HR 3.51 P = 0.137, 95% CI 0.671-18.35). CONCLUSIONS: Our findings support the role of Ki67 as a powerful independent predictor of inferior oncological outcomes in patients with ccRCC. Further prospective studies are needed to determine the clinical applicability of these findings.

Does body mass index impact the outcomes of tubeless percutaneous nephrolithotomy?

OBJECTIVE: To evaluate whether body mass index (BMI) has an impact on the outcomes of tubeless percutaneous nephrolithotomy (PCNL). PATIENTS AND METHODS: We retrospectively reviewed patients who underwent tubeless PCNL at our institution from 2006 to 2011. Specifically, stone-free rates, complications, and hospital length of stay (LOS) were assessed. Patients were divided into four groups based on BMI: <25, 25-29.9, 30-34.9 and ≥35 kg/m(2) . Baseline characteristics and outcomes were compared between BMI groups. Multivariable logistic regressions were used to evaluate the independent contribution of BMI as a predictor of outcomes. RESULTS: We identified 268 patients who fulfilled study requirements. The overall stone-free and complication rates were 52.5% and 19.0%, respectively. Minor and severe complication comprised 10.4% and 8.6%, respectively. Univariate and multivariable analyses showed no association between BMI and stone-free or complication rates. However, patients with a normal BMI had significantly higher transfusion rates (P = 0.005), and were significantly more likely to have a prolonged LOS (≥2 days), when compared with an overweight BMI (P = 0.032) CONCLUSIONS: BMI did not impact the stone-free, or complication rates of tubeless PCNL. Normal BMI was found to be a risk factor for prolonged LOS, which may be due to an increase in clinically significant bleeding in this patient population. Tubeless PCNL appears to be a safe and effective procedure for the treatment of complex renal calculi, independent of BMI.

Utility of noninvasive biomarker testing and MRI to predict a prostate cancer diagnosis.

PURPOSE: To assess the diagnostic performance and utility of the ExoDx IntelliScore and an OPKO4K score to predict prostate cancer in men presenting with elevated PSA-both as independent predictors and in combination with clinical/MRI characteristics. METHODS: Patients with elevated PSA were retrospectively reviewed. Abnormal tests were defined as an OPKO4K score ≥ 7.5% and an ExoDx IntelliScore ≥ 15.6. Four regression models and ROC curves were generated based on: (1) age, PSA, and DRE, (2) model 1 + OPKO4K 4Kscore ≥ 7.5%, (3) model 2 + ExoDx IntelliScore ≥ 15.6, and (4) model 3 + MRI PIRADS 4-5. RESULTS: 359 men received an OPKO4K test, 307 had MRI and 113 had ExoDx tests. 163 men proceeded to prostate biopsy and 196 (55%) were saved from biopsy. Mean age was 65.0 ± 8.7 years and mean PSA was 7.1 ± 6.1 ng/mL. Positive biopsies were found in 84 (51.5%) men. The sensitivity and negative predictive value of an OPKO4K score were 86.7% and 72.3%; values for an ExoDx test were 76.5% and 77.1%, respectively. On regression analysis, clinical markers (Age, PSA, DRE) generated an AUC of 0.559. The addition of an OPKO4K score raised the AUC to 0.653. The stepwise addition of an ExoDx score raised the AUC to 0.766. The combined use of both biomarkers, patient characteristics, and MRI yielded an AUC of 0.825. CONCLUSION: This analysis demonstrates the high negative predictive value of both the OPKO4K score and ExoDX IntelliScore independently while demonstrating that the combination of an OPKO4K score, an ExoDX IntelliScore, and MRI increases predictive capability for biopsy confirmed prostate cancer.

Successful bladder-sparing partial cystectomy for muscle-invasive domal urothelial carcinoma with sarcomatoid differentiation: a case report.

High-grade (HG) urothelial carcinoma (UC) with variant histology has historically been managed conservatively. The presented case details a solitary lesion of muscle-invasive bladder cancer (MIBC) with sarcomatoid variant (SV) histology treated by partial cystectomy (PC) and adjuvant chemotherapy. A 71-year-old male with a 15-pack year smoking history presented after outside transurethral resection of bladder tumor (TURBT). Computerized tomography imaging was negative for pelvic lymphadenopathy, a 2 cm broad-based papillary tumor at the bladder dome was identified on office cystoscopy. Complete staging TURBT noted a final pathology of invasive HG UC with areas of spindle cell differentiation consistent with sarcomatous changes and no evidence of lymphovascular invasion. The patient was inclined toward bladder-preserving options. PC with a 2 cm margin and bilateral pelvic lymphadenectomy was performed. Final pathology revealed HG UC with sarcomatoid differentiation and invasion into the deep muscularis propria, consistent with pathologic T2bN0 disease, a negative margin, and no lymphovascular invasion. Subsequently, the patient pursued four doses of adjuvant doxorubicin though his treatment was complicated by hand-foot syndrome. At 21 months postoperatively, the patient developed a small (<1 cm) papillary lesion near but uninvolved with the left ureteral orifice. Blue light cystoscopy and TURBT revealed noninvasive low-grade Ta UC. To date, the patient has no evidence of HG UC recurrence; 8 years after PC. Patient maintains good bladder function and voiding every 3-4 h with a bladder capacity of around 350 ml. Surgical extirpation with PC followed by adjuvant chemotherapy may represent a durable solution for muscle invasive (pT2) UC with SV histology if tumor size and location are amenable. Due to the sparse nature of sarcomatous features within UC, large multicenter studies are required to further understand the clinical significance and optimal management options for this variant histology.

Preoperative pulmonary embolism does not predict poor postoperative outcomes in patients with renal cell carcinoma and venous thrombus.

PURPOSE: Patients with renal cell carcinoma who present with pulmonary embolism and venous thrombus may not be offered surgery because of presumed poor postoperative outcomes. In this multicenter study we evaluated perioperative mortality, recurrence and cancer specific survival in patients with renal cell carcinoma and venous thrombus diagnosed with preoperative pulmonary embolism. MATERIALS AND METHODS: We reviewed consecutive patient records from our 3 tertiary hospitals to identify patients with renal cell carcinoma and venous thrombus treated with surgery from 2000 to 2011. Univariate and multivariate Cox proportional hazards analysis was used to evaluate whether preoperative pulmonary embolism or other clinical variables were associated with postoperative disease recurrence or cancer specific survival. RESULTS: Pulmonary embolism was identified preoperatively in 35 of 782 patients (4.4%) with renal cell carcinoma. Those with pulmonary embolism preoperatively were more likely to have higher level thrombus and higher T stage (p <0.01). No differences were found in other clinical or pathological features between the groups. There was no difference in 90-day mortality in patients diagnosed with pulmonary embolism preoperatively. Of 395 patients without metastasis preoperatively 147 (37.2%) showed metastatic renal cell carcinoma at a median followup of 22 months. There was no difference in the recurrence rate of renal cell carcinoma in patients with pulmonary embolism (p = 0.36). Recurrence in the lung was not more common in patients with vs without pulmonary embolism preoperatively (p = 0.71). Also, preoperative pulmonary embolism was not predictive of worse cancer specific survival (p = 0.58). CONCLUSIONS: Preoperative pulmonary embolism is not associated with worse early mortality, recurrence or cancer specific survival in patients with renal cell carcinoma and tumor thrombus.

Prognostic role of cell cycle and proliferative biomarkers in patients with clear cell renal cell carcinoma.

PURPOSE: Cell cycle regulatory molecules are implicated in various stages of carcinogenesis. In this proof of principle study we systematically evaluate the association of aberrant expression of cell cycle regulators and proliferative markers and their effect on oncologic outcomes of patients with clear cell renal carcinoma. MATERIALS AND METHODS: Immunohistochemistry for Cyclin D, Cyclin E, p16, p21, p27, p53, p57 and Ki67 was performed on tissue microarray constructs of 452 patients treated with extirpative therapy for clear cell renal cell carcinoma between 1997 and 2010. Clinical and pathological data elements were collected. A prognostic marker score was defined as unfavorable if more than 4 biomarkers were altered. The relationship between marker score and pathological features and oncologic outcomes was evaluated. RESULTS: Median age was 57 years (range 17 to 85) and median followup was 24 months (range 6 to 150). An unfavorable marker score was found in 55 (12.2%) patients and was associated with adverse pathological features. A significant correlation between unfavorable marker score and disease-free survival (HR 26.62, 95% CI 43.38-100.04, p=0.000) and with cancer specific survival (HR 8.15, 95% CI 74.42-101.56, p=0.004) was demonstrated on Kaplan-Meier survival analysis. On multivariate analysis an unfavorable marker score was an independent predictor of disease-free survival (HR 2.63, 95% CI 1.08-6.38, p=0.033). CONCLUSIONS: The cumulative number of aberrantly expressed cell cycle and proliferative biomarkers correlates with aggressive pathological features and inferior oncologic outcomes in patients with clear cell renal cell carcinoma. Our findings indicate that interrogation of cell cycle and proliferative markers is feasible, and further prospective pathway based exploration of biomarkers is needed.

Radical nephroureterectomy for pathologic T4 upper tract urothelial cancer: can oncologic outcomes be improved with multimodality therapy?

PURPOSE: To report the outcomes of patients with pathologic T4 UTUC and investigate the potential impact of peri-operative chemotherapy combined with radical nephroureterectomy (RNU) and regional lymph node dissection (LND) on oncologic outcomes. MATERIALS AND METHODS: Patients with pathologic T4 UTUC were identified from the cohort of 1464 patients treated with RNU at 13 academic centers between 1987 and 2007. Oncologic outcomes were stratified according to utilization of perioperative systemic chemotherapy and regional LND as an adjunct to RNU. RESULTS: The study included 69 patients, 42 males (61%) with median age 73 (range 43-98). Median follow-up was 17 months (range: 6-88). Lymphovascular invasion was found in 47 (68%) and regional lymph node metastases were found in 31 (45%). Peri-operative chemotherapy was utilized in 29 (42%) patients. Patients treated with peri-operative chemotherapy and RNU with LND demonstrated superior oncologic outcomes compared to those not treated by chemotherapy and/or LND during RNU (3Y-DFS: 35% vs. 10%; P = 0.02 and 3Y-CSS: 28% vs. 14%; P = 0.08). In multivariate Cox regression analysis, administration of peri-operative chemotherapy and utilization of LND during RNU was associated with lower probability of recurrence (HR: 0.4, P = 0.01), and cancer specific mortality (HR: 0.5, P = 0.06). CONCLUSIONS: Pathological T4 UTUC is associated with poor prognosis. Peri-operative chemotherapy combined with aggressive surgery, including lymph node dissection, may improve oncological outcomes. Our findings support the use of aggressive multimodal treatment in patients with advanced UTUC.

Postoperative Psychological Impact on Teenagers after Gynecomastia Correction.

Gynecomastia is common among teenagers. Most published research focused on how surgery is effective in enhancing the aesthetic appearance of the breast. Limited information is already known about the psychosocial benefits of surgical interventions. This study explores and assesses the surgical, cosmetic, and psychological outcome of gynecomastia correction in teenagers. Methods: This prospective study included 20 teenagers with Simon grade IIA gynecomastia. The assessment included complications, patients' satisfaction, Manchester Scar Scale, and Li et al questionnaire at 12 months postoperative. Rosenberg Self-Esteem Scale, 36-Item Short Form Survey (SF-36) for quality of life, and school achievement level were evaluated 1 month preoperative and 12 months postoperative. Statistical analysis was done. Results: Patients were aged 13-19 years old. The follow-up period was 12 ± 36 months. Postoperative complications included seroma formation (n = 1) and mild asymmetry (n = 3). Results were "uniformly good to excellent" on a satisfaction scale. The Manchester Scar Scale shows the lowest score, which denotes the highest outcomes. The Li et al questionnaire showed a positive overall change. Comparing Rosenberg Scale scores pre- and postoperatively revealed higher scores postoperatively, which indicate higher self esteem. Comparing SF-36 pre- and postoperatively showed a significant increase in postoperative quality of life. Comparing school achievement pre- and postoperatively showed marked improvement postoperatively. Results were highly statistically significant. Conclusions: Surgical treatment of teenage gynecomastia is beneficial for different psychosocial domains. Pull-through of the mammary gland combined with liposuction provides satisfactory cosmetic results. Patients who underwent surgery reported a significant improvement in psychosocial load, better school achievement, higher quality of life, and better self-esteem.

Residual fragments following ureteroscopic lithotripsy: incidence and predictors on postoperative computerized tomography.

PURPOSE: Residual fragments following ureteroscopy for calculi may contribute to stone growth, symptoms or additional interventions. We reviewed our experience with ureteroscopy for calculus disease to define the incidence and establish factors predictive of residual fragments. MATERIALS AND METHODS: Records associated with 667 consecutive ureteroscopic lithotripsy procedures for upper urinary calculi were reviewed. In 265 procedures (40%) computerized tomography was done between 30 and 90 days postoperatively. They comprised the study group. Residual fragments were defined as any residual ipsilateral stone greater than 2 mm. RESULTS: Included in the study were 121 men and 127 women with a mean age of 47 years. Mean target stone diameter was 7.6 mm. The stone location was the kidney in 30% of cases, ureter in 50%, and kidney and ureter in 20%. Residual fragments were detected on computerized tomography after 101 of 265 procedures (38%). Pretreatment stone size was associated with residual fragments at a rate of 24%, 40% and 58% for stones 5 or less, 6 to 10 and greater than 10 mm, respectively (p <0.001). Additionally, stone location in the kidney (p <0.001) or the kidney and ureter (p = 0.044), multiple calculi (p = 0.003), longer operative time (p = 0.008) and exclusive use of flexible ureteroscopy (p = 0.029) were associated with residual fragments. In a multivariate model only pretreatment stone diameter greater than 5 mm was independently associated with residual fragments after ureteroscopy (diameter 6 to 10 and greater than 10 mm OR 2.03, p = 0.03 and OR 3.74, p = 0.003, respectively). CONCLUSIONS: Of patients who underwent ureteroscopic lithotripsy for calculi 38% had residual fragments by computerized tomography criteria, including more than 50% with stones 1 cm or greater. Such data may guide expectations regarding the success of ureteroscopy in attaining stone-free status.