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.

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.

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.

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.

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.

Biotin-thiamine responsive basal ganglia disease in the era of COVID-19 outbreak diagnosis not to be missed: A case report.

BACKGROUND: Biotin-thiamine-responsive basal ganglia disease (BTRBGD) is a rare treatable autosomal recessive neurometabolic disorder characterized by progressive encephalopathy that eventually leads to severe disability and death if not treated with biotin and thiamine. BTRBGD is caused by mutations in the SLC19A3 gene on chromosome 2q36.6, encoding human thiamine transporter 2 (hTHTR2). Episodes of BTRBGD are often triggered by febrile illness. CASE REPORT: The patient was 2 years 10 months old male child presented with fever and progressive acute encephalopathy associated with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus infection. MRI revealed bilateral symmetrical high signal involving both basal ganglia and medial thalami which is swollen with central necrosis, initially diagnosed as acute necrotizing encephalomyelitis with increased severity. Genetic analysis revealed BTRBGD. CONCLUSION: BTRBGD requires high index of suspicion in any patient presenting with acute encephalopathy, characteristic MRI findings (that are difficult to differentiate from necrotizing encephalopathy), regardless of the existence of a proven viral infection.

Metabolic diagnoses of recurrent stone formers: temporal, geographic and gender differences.

BACKGROUND: Metabolic factors underlying the recent increase in stone prevalence over the past decades are not well understood. Herein, we evaluate temporal, geographic and gender-specific trends in metabolic risk factors in recurrent kidney stone formers. PATIENTS AND METHODS: A systematic literature review of metabolic risk factors for stone formation was conducted, inclusive of the last four decades. Studies with inadequate 24 h urine metabolic data, pediatric or those with less than 50 patients were excluded. The primary outcome was prevalence of each metabolic risk factor, compared between studies published prior to the year 2000 vs those following. Geographic and gender differences were secondary outcomes. RESULTS: Twenty-eight articles met inclusion criteria, of which 10 (n = 1578) were published prior to the year 2000 and 18 (n = 8747) were published thereafter. Comparing these groups, an increase in hyperoxaluria (29% vs 33%; p = 0.002), hypercalciuria (35 vs 36%; p = 0.446), hyperuricosuria (17% vs 22%; p < 0.0001), low urine volume (28 vs 38%; p < 0.0001) and hypocitraturia (23% vs 44%; p < 0.0001) was observed. The prevalence of hyperoxaluria, hypercalciuria, hyperuricosuria and hypocitraturia were significantly higher in males. There were also significant geographical differences, with higher prevalence of hyperoxaluria and hypocitraturia in non-Western countries and higher prevalence of hypercalciuria in Western countries. Prevalence of hyperoxaluria is increasing in the US. CONCLUSION: Prevalence of metabolic risk factors for nephrolithiasis significantly increased in recent years. These findings are hypothesis-generating and may provide valuable insight into the epidemiology, prevention and management of recurrent stone disease. Dietary modifications and innovative medical therapies are needed to decrease metabolic risk factors underlying nephrolithiasis.

Rising occurrence of hypocitraturia and hyperoxaluria associated with increasing prevalence of stone disease in calcium kidney stone formers.

OBJECTIVE: To evaluate metabolic risk factors in calcium kidney stone formers from two different decades, comparing changes in metabolic profiles over time. METHODS: A retrospective analysis was performed of calcium kidney stone formers who underwent metabolic evaluation of urolithiasis with 24-hour urine collections at a single institution. There were 309 patients evaluated from 1988 to 1994 (Group A), and 229 patients from 2007 to 2010 (Group B). A comparison between both groups was performed to assess changes in demographics and in metabolic stone profiles. RESULTS: Comparing Group A to Group B, the percentage of females increased from 43 to 56%, obese patients (BMI ≥ 30) increased from 22 to 35%, and patients ≥ 50 years increased from 29 to 47% (all p < 0.005). A greater percentage of patients had hypocitraturia in the recent cohort (46-60%, p = 0.001), with hypocitraturia significantly more frequent in obese patients (p = 0.005). Hyperoxaluria was also increased in Group B compared to Group A (23-30% p = 0.07), a finding that was significant in males (32-53%, p = 0.001). CONCLUSIONS: Urolithiasis has increased in females, obese, and older patients, consistent with population-based studies. We report a rising incidence of hypocitraturia and hyperoxaluria in the contemporary cohort, particularly in obese patients and in males, respectively. Further studies are needed to better characterize the metabolic changes corresponding to the increase in stone disease.

A California Cancer Registry Analysis of Urothelial and Non-urothelial Bladder Cancer Subtypes: Epidemiology, Treatment, and Survival.

INTRODUCTION: We evaluated epidemiologic trends and survival for bladder cancer histologic subtypes in California patients by comparing urothelial carcinoma of the bladder (UCB) and non-urothelial subtypes including squamous cell carcinoma (SCC), adenocarcinoma (ADC), and small-cell carcinoma (SmCC). MATERIALS AND METHODS: The California Cancer Registry (CCR) was queried for incident bladder cancer cases from 1988 to 2012. Epidemiologic trends based on tumor histology were described. The primary outcome was disease-specific survival (DSS). Kaplan-Meier and multivariable Cox regression survival analyses were performed. RESULTS: A total of 72,452 bladder cancer cases (66,260 UCB, 1390 SCC, 587 ADC, 370 SmCC, and 3845 other) were included. The median age was 72 years (range, 18-109 years). ADC was more common in younger patients. Male:female ratios varied among cancer types (3.1:1 in UCB, 2.9:1 in SmCC, 1.6:1 in ADC, and 0.9:1 in SCC). Most non-urothelial cases (> 60%) presented at advanced stages, whereas most UCB cases (80.6%) were localized. Kaplan-Meier analysis revealed the best 5-year DSS and overall survival (OS) in UCB, whereas the worst outcomes were seen with SCC and SmCC (P < .0001). Multivariable analysis controlling for age, gender, tumor stage, and grade demonstrated that non-urothelial histologic subtypes were associated with significantly worse DSS compared with UCB (SCC hazard ratio [HR], 2.612; SmCC HR, 1.641; and ADC HR, 1.459; P < .0001). CONCLUSIONS: Non-urothelial bladder cancers have worse oncologic outcomes than UCB in California patients. SCC and SmCC are associated with the worst DSS based on univariable and multivariable analyses.

Racial and Socioeconomic Disparities in Bladder Cancer Survival: Analysis of the California Cancer Registry.

PURPOSE: To examine the California Cancer Registry (CCR) for bladder cancer survival disparities based on race, socioeconomic status (SES), and insurance in California patients. PATIENTS AND METHODS: The CCR was queried for bladder cancer cases in California from 1988 to 2012. The primary outcome was disease-specific survival (DSS), defined as the time interval from date of diagnosis to date of death from bladder cancer. Survival analyses were performed to determine the prognostic significance of racial and socioeconomic factors. RESULTS: A total of 72,452 cases were included (74.5% men, 25.5% women). The median age was 72 years (range, 18-109 years). The racial distribution among the patients was 81% white, 3.8% black, 8.8% Hispanic, 5.2% Asian, and 1.2% from other races. In black patients, tumors presented more frequently with advanced stage and high grade. Medicaid patients tended to be younger and had more advanced-stage, higher-grade tumors compared to patients with Medicare or managed care (P < .0001). Kaplan-Meier analysis demonstrated significantly poorer 5-year DSS in black, low SES, and Medicaid patients (P < .0001). When controlling for stage, grade, age, and gender, multivariate analysis revealed that black race (DSS hazard ratio = 1.295; 95% confidence interval, 1.212-1.384), low SES (DSS hazard ratio = 1.325; 95% confidence interval, 1.259-1.395), and Medicaid insurance (DSS hazard ratio = 1.349; 95% confidence interval, 1.246-1.460) were independent prognostic factors (P < .0001). CONCLUSION: An analysis of the CCR demonstrated that black race, low SES, and Medicaid insurance portend poorer DSS. These findings reflect a multifaceted socioeconomic and public health conundrum, and efforts to reduce inequalities should be pursued.

Expression and prognostic utility of PD-L1 in patients with squamous cell carcinoma of the bladder.

OBJECTIVES: Checkpoint inhibitors are approved for the treatment of urothelial bladder cancer. However, there have been no reports on the prognostic value of programmed-death receptor ligand 1 (PD-L1) expression in squamous cell carcinoma (SCC) of the bladder. We assessed the relationship between PD-L1 expression, clinicopathological features, and oncologic outcomes in bladder SCC. METHODS AND MATERIALS: Immunohistochemistry of PD-L1 was performed on 151 radical cystectomy specimens with pure SCC treated in Mansoura, Egypt from 1997 to 2004. RESULTS: Median patient age was 52 years (range: 36-74 years) and median length of follow up was 63 months (range: 1-100 months). Schistosomiasis was present in 81% of the specimens and 93% had muscle-invasive disease on pathologic staging. PD-L1 expression was negative in 50 (33%) of the specimens. Negative PD-L1 expression was associated with higher pathologic tumor stage (P = 0.04), higher grade lesions (P = 0.01), and the presence of lymphovascular invasion (P < 0.01). Kaplan-Meier analyses showed that negative PD-L1 expression is associated with worse recurrence-free (P = 0.01) and worse cancer-specific survival (P = 0.01). Multivariable Cox regression analyses showed negative PD-L1 expression was an independent predictor of disease recurrence (hazards ratio 2.05, 95% confidence interval 1.06-3.96, P = 0.03) and cancer-specific mortality (hazards ratio 2.89, 95% confidence interval 1.22-6.82, P = 0.02). CONCLUSIONS: Negative PD-L1 expression is associated with higher pathologic tumor stage, higher grade lesions, presence of lymphovascular invasion, and worse oncologic outcomes after radical cystectomy for SCC. These findings support the need for the inclusion of patients with bladder SCC into immunotherapy clinical trials.

Antibiotic Utilization Before Endourological Surgery for Urolithiasis: Endourological Society Survey Results.

INTRODUCTION: Ureteroscopy (URS) and percutaneous nephrolithotomy (PCNL) are common procedures performed to treat kidney stones. Despite advances in technology/technique, serious infectious complications can occur. To better understand the preoperative antibiotic administration patterns and adherence to guidelines from the American Urological Association (AUA) and the European Association of Urology (EAU), members of the Endourological Society were sent a clinical vignette-based survey to assess the antibiotic use in a variety of pre-URS and pre-PCNL scenarios. METHODS: Endourological Society members were e-mailed a survey that queried antibiotic therapy duration before uncomplicated URS and PCNL with negative and asymptomatic positive preoperative urine cultures (PUCs). For negative PUC questions, selecting more perioperative antibiotics was considered a "prolonged" course as it extends past the maximum of 24-hour perioperative prophylaxis recommended by both the AUA and EAU. RESULTS: The response rate was 16.3% for a total of 326 responders. Twenty-one percent to 39% of respondents reported giving prolonged courses of preoperative antibiotics before a URS or PCNL with a negative PUC (p < 0.0001). When presented with a negative PUC, more prolonged antibiotic courses were reported with the following hierarchy: PCNL for 2 cm intrarenal stones (39%) > URS for 12 mm renal pelvis stone (28%) > URS for 7 mm distal ureteral stones (21%) (p < 0.0001). In both negative and positive PUC questions, differences were noted in preoperative antibiotic prescribing patterns among site of practice (United States, Canada, Europe, Asia, South America, and Others), type of practice (academic vs all others), years in practice (<10 or ≥10 years), and surgical volume (URS and PCNL >100 or ≤100 annual cases). CONCLUSIONS: Adherence to guidelines on antibiotic administration before PCNL and URS with a negative PUC varies by scenario and provider. In 21% to 39% of negative PUC cases, reported antibiotic use before a URS or PCNL is not consistent with recommendations from the AUA and EAU. Before a positive PUC URS or PCNL, nearly all surveyed provide preoperative antibiotics; however, the regimen length is variable.

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.

A Review of Molecular Predictors of Response to Neoadjuvant Chemotherapy in Muscle-invasive Bladder Cancer.

Locally advanced, muscle-invasive urothelial carcinoma of the bladder (MIBC) may be definitively treated with either radiotherapy or radical cystectomy (RC) with urinary diversion. Neoadjuvant chemotherapy (NAC) is typically administered prior to treatment with either modality. Receiving NAC prior to RC might confer a survival advantage compared to undergoing RC alone. However, its usefulness has been questioned due to concerns about over treatment and toxicity. Having the ability to predict whether individual patients would benefit from or be harmed by NAC would be an important tool in precision medicine. Unfortunately, to date no prognostic or predictive molecular markers have been validated for this purpose. In this manuscript, we review the current state of molecular markers in MIBC treatment and outline how recent advances in whole-genome sequencing may soon improve the selection of precisely targeted therapeutics for the benefit of individual patients.

Skin-to-tumor Distance Predicts Treatment Failure of T1A Renal Cell Carcinoma Following Percutaneous Cryoablation.

OBJECTIVE: To determine the impact of skin-to-tumor (STT) distance on the risk for treatment failure following percutaneous cryoablation (PCA). METHODS: We retrospectively reviewed patients who underwent PCA with documented T1a recurrent renal cell carcinoma (RCC) at 2 academic centers between 2005 and 2015. Patient demographics, tumor characteristics, and perioperative and postoperative course variables were collected. Additionally, we measured the STT distance by averaging the distance from the skin to the center of the tumor at 0°, 45°, and 90° on preoperative computed tomography imaging. RESULTS: We identified 86 patients with documented T1a RCC. The mean age at the time of surgery was 69 years (range: 37-91 years), and the mean tumor size was 2.7 cm (range: 1.0-4.0 cm). With a mean follow-up of 24 months (range: 3-63 months), 11 (12.8%) treatment failures occurred. Patients with treatment failure had significantly higher mean STT distance than those without: 11.0 cm (range: 6.3-20.1 cm) compared to 8.4 cm (range: 4.4-15.2 cm), respectively (P = .002). STT distance was an independent predictor of treatment failure (odds ratio: 1.32, 95% confidence interval: 1.04-1.69, P = .029). STT distance greater than 10 cm had a fourfold increased risk of tumor treatment failure (odds ratio: 4.43, 95% confidence interval: 1.19-16.39, P = .018). Tumor size, R.E.N.A.L. Nephrometry score, and number of cryoprobes placed were not associated with treatment failure. CONCLUSION: STT, an easily measured preoperative variable, may inform the risk of RCC treatment failure following PCA.

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.

Predictors of Complications After Percutaneous Image-Guided Renal Cryoablation for T1a Renal Cortical Neoplasms.

PURPOSE: To determine the incidence and predictors of major complications in patients undergoing percutaneous cryoablation (PCA) for small renal masses. METHODS: We performed a retrospective analysis of patients undergoing PCA from 2005 to 2012. We analyzed demographic, radiographic, and complication data. We defined complications as any deviation from the expected postoperative course. We determined predictors of complications. RESULTS: A total of 190 patients were included in the study. The mean age was 69 years, and 132 (69%) were males. The mean tumor diameter was 2.2 cm (0.8-4.0 cm). The mean number of probes utilized per procedure was 2.3. We observed 16 (8.4%) complications including 14 Clavien grade I, which includes 6 (2%) large renal/retroperitoneal hematomas, 4 (2%) pneumothoraxes, 2 (1%) urinary tract infections, and 2 (1%) atrial fibrillations. There were two (1%) Clavien grade II complications (intestinal perforations). In univariable analysis, larger tumors and more probes were associated with higher risk of complications (all ps < 0.05). In multivariable analysis, larger tumor dimension (odds ratio [OR] = 2.85; 95% confidence interval [CI] = 1.34, 6.05; p = 0.006) was independently associated with major complications. After multivariable adjustments for patient's characteristics such as age, gender, American Society of Anesthesiologists, year of surgery, and histopathology, larger tumor dimension (OR = 2.85; 95%CI = 1.34, 6.05; p = 0.006) and more cryoablation probes (OR = 1.94; 95%CI = 1.36, 2.75; p < 0.001) were independently associated with higher risk of major complications. CONCLUSIONS: In a cohort of patients undergoing PCA for T1a small renal mass, larger tumor dimension and more cryoablation probes were independently associated with higher risk of complication. Although PCA is relatively safe and the major complications are infrequent, careful patient selection is crucial.

Should metabolic evaluation be performed in patients with struvite stones?

Previous studies suggested that patients with pure struvite calculi rarely have underlying metabolic abnormalities. Therefore, most of these patients do not undergo metabolic studies. We report our experience with these patients and their response to directed medical therapy. Between 1/2005 and 9/2012, 75 patients treated with percutaneous nephrolithotomy for struvite stones were identified. Of these, 7 had pure struvite stones (Group 1), 32 had mixed struvite stones (Group 2), both with metabolic evaluation, and 17 had pure struvite stones without metabolic evaluation (Group 3). The frequency of metabolic abnormalities and stone activity (defined as stone growth or stone-related events) was compared between groups. The median age was 55 years and 64 % were female. No significant difference in race, infection history, family history, stone location or volume existed between groups. Metabolic abnormalities were found in 57 % of Group 1 and 81 % of Group 2 patients. A similar proportion of Group 1 and 2 patients received modification to or continuation of metabolic therapy, whereas no Group 3 patients received any directed therapy. In patients with >6 months follow-up, the stone activity rate between Groups 1 and 2 appeared similar whereas Group 3 trended towards higher stone activity rate. Metabolic abnormalities in pure struvite stone formers appear to be more common than previously reported. Directed medical therapy in these patients may reduce stone activity. The role of metabolic evaluation and directed medical therapy needs reconsideration in patients with pure struvite stones.

Squamous cell carcinoma of the urinary bladder: Systematic review of clinical characteristics and therapeutic approaches.

OBJECTIVE: To highlight the current understanding of the epidemiology, clinicopathological characteristics, and management of squamous cell carcinoma (SCC) of the bladder, as it accounts for 2-5% of bladder tumours, with a focus on non-bilharzial-associated SCC (NB-SCC). The standard treatment for bladder SCC remains radical cystectomy (RC). We present an updated clinical profile of bladder SCC and a review of NB-SCC therapeutic approaches, including RC, neoadjuvant and adjuvant treatments, radiotherapy, chemotherapy, and immunotherapy. METHODS: Using search terms relating to SCC, urinary bladder, and treatment modalities, we performed a search of the PubMed and Embase databases to identify NB-SCC treatment approaches and outcomes. Peer-reviewed English language reports from 1975 to present assessing SCC management were included. Two authors independently screened and extracted the data. RESULTS: Of the 806 articles screened, 10 met the pre-defined inclusion criteria. RC was performed in seven of the 10 studies. Although radiotherapy alone yielded poor outcomes, preoperative radiotherapy and RC were associated with improved survival. There is little evidence supporting the use of chemotherapy in NB-SCC, and its efficacy in relation to RC is not known. CONCLUSION: Based on current literature, there is insufficient evidence to provide a treatment recommendation for NB-SCC. Whilst RC is the standard of care, the role of preoperative radiotherapy should be revisited and compared to RC alone. Additional studies incorporating multimodal approaches, contemporary radiation techniques, and systemic therapies are warranted. Immunotherapy as a treatment for bladder SCC has yet to be investigated.

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.