Localised non-metastatic sarcomatoid renal cell carcinoma: a 31-year externally verified study.

OBJECTIVE: To evaluate post-nephrectomy outcomes and predictors of cancer-specific survival (CSS) between patients with localised sarcomatoid renal cell carcinoma (sRCC) and those with Grade 4 RCC (non-sRCC), as most sRCC research focuses on advanced or metastatic disease with limited studies analysing outcomes of patients with localised non-metastatic sRCC. PATIENTS AND METHODS: A total of 564 patients with localised RCC underwent partial or radical nephrectomy between June 1988 to March 2019 for sRCC (n = 204) or World Health Organization/International Society of Urological Pathology Grade 4 non-sRCC (n = 360). The CSS at every stage between groups was assessed. Phase III ASSURE clinical trial data were used to externally validate the CSS findings. The Mann-Whitney U-test and chi-squared test compared outcomes and the Kaplan-Meier method evaluated CSS, overall survival (OS) and recurrence-free survival. Clinicopathological features associated with RCC death were evaluated using Cox proportional hazards regression. RESULTS: The median follow-up was 31.5 months. The median OS and CSS between the sRCC and Grade 4 non-sRCC groups was 45 vs 102 months and 49 vs 152 months, respectively (P < 0.001). At every stage, sRCC had worse CSS compared to Grade 4 non-sRCC. Notably, pT1 sRCC had worse CSS than pT3 Grade 4 non-sRCC. Negative predictors of CSS were sarcomatoid features, non-clear cell histology, positive margins, higher stage (pT3/pT4), and use of minimally invasive surgery (MIS). ASSURE external verification showed worse CSS in patients with sRCC (hazard ratio [HR] 1.63, 95% confidence interval [CI] 1.12-2.36; P = 0.01), but not worse outcomes in MIS surgery (HR 1.39, 95% CI 0.75-2.56; P = 0.30). CONCLUSIONS: Localised sRCC had worse CSS compared to Grade 4 non-sRCC at every stage. Negative survival predictors included positive margins, higher pathological stage, use of MIS, and non-clear cell histology. sRCC is an aggressive variant even at low stages requiring vigilant surveillance and possible inclusion in adjuvant therapy trials.

A combined MRI-PSAD risk stratification system for prioritizing prostate biopsies.

INTRODUCTION:   Prostate cancer screening with PSA is associated with low specificity; furthermore, little is known about the optimal timing of biopsy.  We aimed to evaluate whether a risk classification system combining PSA density (PSAD) and mpMRI can predict clinically significant cancer and determine biopsy timing. MATERIALS AND METHODS:  We reviewed the medical records of 256 men with a PI-RADS ≥ 3 lesion on mpMRI who underwent transperineal targeted and systematic biopsies of the prostate between 2017-2019.  Patients were stratified into three risk groups based on PSAD and mpMRI findings. The study endpoint was clinically significant prostate cancer (CSPC).  The association between the risk groups and CSPC was evaluated. RESULTS:  Based on the proposed risk stratification system 42/256 men (16%) were high-risk (mpMRI finding of extra-prostatic extension and/or seminal vesicle invasion and/or a PI-RADS 5 lesion with a PSAD > 0.15 ng/mL²), 164/256 (64%) intermediate-risk (PI-RADS 4-5 lesions and/or PSAD > 0.15ng/mL² with no high-risk features) and 50/256 (20%) low-risk (PI-RADS 3 lesions and PSAD ≤ 0.15 ng/mL²).  High-risk patients had significantly higher rates of CSPC (76%) when compared to intermediate-risk (26%) and low-risk (4%).  On multivariable logistic regression analysis adjusted for age, previous biopsy, and clinical T-stage we found an association between intermediate-risk (OR = 4.84, p = 0.038) and high-risk (OR = 40.13, p < 0.001) features and CSPC.  High-risk patients had a shorter median biopsy delay time (110 days) compared to intermediate- and low-risk patients (141 and 147 days, respectively).  We did not find an association between biopsy delay and CSPC. CONCLUSIONS:   Our findings suggest that a three-tier risk classification system based on mpMRI and PSAD can identify patients at high-risk for CSPC who may benefit from earlier biopsy.

Complete Blood Count Markers and C-Reactive Protein as Predictors of Testicular Viability in the Event of Testicular Torsion in Adults.

INTRODUCTION: The association between blood markers and testicular viability after testicular torsion (TT) is not well known. We evaluated the role of complete blood count markers and C-reactive protein (CRP) in predicting testicular viability after TT. METHODS: Fifty men, ≥18 years of age, operated for TT between the years 2015-2020 were enrolled. Blood markers including neutrophil-, lymphocyte-, and platelet count, and CRP were obtained. Neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were calculated. The study outcome was testicular salvage. RESULTS: Median age was 23 years (interquartile range [IQR]: 21, 31). Median duration of torsion was 10 h (IQR: 6, 42). Sonographic texture of the testis was homogenous in 27 (56%) patients and heterogenous in 21 (44%). During scrotal exploration, 36 patients (72%) underwent orchiopexy and 14 (28%) underwent orchiectomy. Patients who underwent orchiopexy were younger (22 years vs. 31 years, p = 0.009), had a shorter duration of torsion (median 8 h vs. 48 h, p < 0.001), and a homogenous texture on scrotal ultrasound (76.5 vs. 7.1%, p < 0.001). Median NLR, PLR, and CRP were higher among patients who underwent orchiectomy; however, these differences did not reach statistical significance. Patients with heterogenous echotexture were significantly more likely to undergo orchiectomy (odds ratio = 42, 95% confidence interval: 7, 831, adjusted p value = 0.009). CONCLUSIONS: We found no association between blood-based biomarkers and testicular viability after TT; however, testicular echotexture significantly predicted outcome.

Association between early change in neutrophil-to-lymphocyte ratio after radical cystectomy and treatment outcomes.

OBJECTIVES: To evaluate the associations of peri-operative neutrophil-to-lymphocyte ratio (NLR) and change in NLR with survival after radical cystectomy. PATIENTS AND METHODS: We retrospectively reviewed a multicentre cohort of patients with bladder cancer who underwent radical cystectomy between 2010 and 2020. Preoperative NLR, postoperative NLR, delta-NLR (postoperative minus preoperative NLR) and NLR change (postoperative divided by preoperative NLR) were calculated. Patients were stratified based on elevation of preoperative and/ or postoperative NLR above the median values. Multivariable Cox regression models were used to evaluate the associations of peri-operative NLR and NLR change with survival. RESULTS: The study cohort included 346 patients with a median age of 69 years. The median (interquartile range) preoperative NLR, postoperative NLR, delta-NLR and NLR change were 2.55 (1.83, 3.90), 3.33 (2.21, 5.20), 0.43 (-0.50, 2.08) and 1.2 (0.82, 1.96), respectively. Both preoperative and postoperative NLR were elevated in 110 patients (32%), 126 patients (36%) had an elevated preoperative or postoperative NLR, and 110 patients (32%) did not have an elevated NLR. On multivariable analysis, increased preoperative and postoperative NLR were significantly associated with decreased survival. While delta-NLR and NLR change were not associated with outcome, patients with elevations in both preoperative and postoperative NLR had the worst overall (hazard ratio [HR] 2.97, 95% confidence interval [CI] 1.78, 4.95; P < 0.001) and cancer-specific survival rates (HR 2.41, 95% CI 1.3, 4.4; P = 0.004). CONCLUSIONS: Preoperative and postoperative NLR are significant predictors of survival after radical cystectomy; patients in whom both NLR measures were elevated had the worst outcomes. Future studies should evaluate whether an increase in NLR during long-term follow-up may precede disease recurrence.

The association between modifiable perioperative parameters and renal function after nephrectomy.

OBJECTIVE: To evaluate the association between intraoperative anaesthetic parameters, primarily intraoperative hypotension, and postoperative renal function in patients undergoing nephrectomy. PATIENTS AND METHODS: We reviewed data from 3240 consecutive patients who underwent nephrectomy between 2010 and 2018. Anaesthetic parameters evaluated included duration of hypotension, tachycardia, hypothermia, volatile anaesthetic use and mean arterial pressure in the post-anaesthesia care unit. Outcomes included acute kidney injury (AKI) and estimated glomerular filtration rate (eGFR) within the first year after nephrectomy. Associations between anaesthetic parameters and outcomes were evaluated with multivariable logistic regression and generalised estimating equation, respectively, adjusted for predictors of renal function after nephrectomy. RESULTS: Before nephrectomy, 677 (21%) patients had moderate-severe chronic kidney disease. A quarter of patients (n = 809) had postoperative AKI and 35% (n = 746) had Stage ≥3 chronic kidney disease 12-months after surgery. Only 12% of patients (n = 386) had >5 min of intraoperative hypotension. While not statistically significant, longer duration of intraoperative hypotension was associated with slightly higher rates of AKI (odds ratio [OR] per 10-min 1.14, 95% confidence interval [CI] 0.98, 1.32). Prolonged hypothermia was associated with increased rate of AKI (OR per 10-min 1.02, 95% CI 1.00, 1.04), and decreased eGFR (change in eGFR per 10-min -0.19, 95% CI -0.27, -0.12); however, these results have limited clinical significance. CONCLUSIONS: Under current practice, intraoperative anaesthetic parameters are tightly maintained, restricting the significance of their effect on postoperative renal function. Future studies should evaluate whether haemodynamic parameters during the early postoperative period, when they are monitored less frequently, are associated with renal functional outcome.

Querying the significance of patient position during computerized tomography on the reliability of pre-percutaneous nephrolithotomy planning.

BACKGROUND: Computerized tomography (CT) is considered indispensable in percutaneous nephrolithotomy (PCNL) planning. We aimed to define the reliability of pre-PCNL CT for planning renal access by assessing renal positional changes between supine and prone CTs. SUBJECTS AND METHODS: CT urographies (CTU) of 30 consecutive patients were reviewed for distances upper pole (UP)-diaphragm, UP-diaphragm attachment, renal pelvis (RP)-lateral body wall, RP- posterior body wall, and lower pole (LP)- anterior-superior iliac spine (ASIS). The posterior and lateral renal axes angles were also calculated. RESULTS: The most consistent overall movement in transition from prone to supine was backward rotation, as demonstrated by a decrease in distance UP-posterior body wall (p = 0.010) and increase in the posterior renal angle (p < 0.0001). This finding correlated with the patient's body mass index (BMI) (p = 0.029). The left kidney was more mobile than the right one, moving significantly for five of the measured parameters compared to the right kidney which moved significantly for only two parameters. The UP-diaphragm distance of the left kidney correlated with age (p = 0.014), the RP-lateral wall distance correlated with previous abdominal surgery (p = 0.006), and the RP-posterior wall distance with BMI (p = 0.017). On the right, the UP-diaphragm distance correlated with gender (p = 0.002) and the lateral renal rotation was smaller (p = 0.046). CONCLUSIONS: Kidneys present significant mobility between supine and prone positions. CT assessment should be performed in the position expected during surgery and should be interpreted with caution, while a real-time imaging modality should be used in the operating room.

Fascial dehiscence after radical cystectomy: Is abdominal exploration mandatory?

BACKGROUND: Fascial dehiscence after radical cystectomy may have serious clinical implications. To optimize its management, we sought to describe accompanying intraabdominal findings of post-cystectomy dehiscence repair and determine whether a thorough intraabdominal exploration during its operation is mandatory. METHODS: We retrospectively reviewed a multi-institutional cohort of patients who underwent open radical cystectomy between 2005 and 2020. Patients who underwent exploratory surgery due to fascial dehiscence within 30 days post-cystectomy were included in the analysis. Data collected included demographic characteristics, the clinical presentation of dehiscence, associated laboratory findings, imaging results, surgical parameters, operative findings, and clinical implications. Potential predictors of accompanying intraabdominal complications were investigated. RESULTS: Of 1301 consecutive patients that underwent cystectomy, 27 (2%) had dehiscence repair during a median of 7 days post-surgery. Seven patients (26%) had accompanying intraabdominal pathologies, including urine leaks, a fecal leak, and an internal hernia in 5 (19%), 1 (4%), and 1 (4%) patients, respectively. Accompanying intraabdominal findings were associated with longer hospital stay [20 (IQR 17, 23) vs. 41 (IQR 29, 47) days, P = 0.03] and later dehiscence identification (postoperative day 7 [IQR 5, 9] vs. 10 [IQR 6, 15], P = 0.03). However, the rate of post-exploration complications was similar in both groups. A history of ischemic heart disease was the only predictor for accompanying intraabdominal pathologies (67% vs. 24%; P = 0.02). CONCLUSIONS: A substantial proportion of patients undergoing post-cystectomy fascial dehiscence repair may have unrecognized accompanying surgical complications without prior clinical suspicion. While cardiovascular disease is a risk factor for accompanying findings, meticulous abdominal inspection is imperative in all patients during dehiscence repair. Identification and repair during the surgical intervention may prevent further adverse, possibly life-threatening consequences with minimal risk for iatrogenic injury.

Asymptomatic bacteriuria and antibiotic resistance profile in children with neurogenic bladder who require clean intermittent catheterization.

STUDY DESIGN: A retrospective cohort study. OBJECTIVES: To document the prevalence of asymptomatic bacteriuria and to characterize the resistance patterns to antibiotics among children with neurogenic bladder who require clean intermittent catheterization, with an emphasis on multidrug resistance. SETTING: A national referral pediatric and adolescent rehabilitation facility in Jerusalem, Israel. METHODS: Routine urine cultures were collected before urodynamic studies in suitable individuals during 2010-2018. None of them had symptoms of urinary tract infection at the time of specimen collection. Cultures were defined as being positive if a single bacterial species was isolated together with a growth of over 105 colony-forming units/ml. Resistance patterns were defined as extended-spectrum beta-lactamase (ESBL) and resistant to 3 antimicrobial groups (multi-drug resistant, MDR). RESULTS: In total, 281 urine cultures were available for 186 participants (median age 7 years, range 0.5-18). Etiologies for CIC included myelomeningocele (n = 137, 74%), spinal cord injury (n = 16, 9%) and caudal regression syndrome (n = 9, 5%). Vesicoureteral reflux was diagnosed in 36 participants (19%), 14 of whom were treated with prophylactic antibiotics. Asymptomatic bacteriuria was present in 217 specimens (77%, 95%CI [0.72-0.82]). The bacteria species were E. coli (71%), Klebsiella (13%), and Proteus (10%). ESBL was found in 11% of the positive cultures and MDR in 9%, yielding a total of 34 (16% of positive cultures) positive for ESBL and/or MDR bacteria. CONCLUSIONS: Asymptomatic bacteriuria and resistance to antimicrobials are common in pediatric individuals who require CIC.

Flexible Cystoscopy in the Setting of Macroscopic Hematuria: Do the Findings Justify Its Use?

BACKGROUND: Patients hospitalized due to gross hematuria frequently complete evaluation in the outpatient setting. The use of office flexible cystoscopy during hospitalization may lead to prompt diagnosis and treatment but can be limited due to low visualization and artifacts that can hamper diagnostic ability. OBJECTIVE: The objective of this study was to assess flexible cystoscopy findings and yield performed in patients hospitalized due to gross hematuria. METHODS: Medical records of patients who underwent flexible cystoscopy while hospitalized during September 2018-December 2019 were reviewed. Cystoscopic findings were categorized into (1) suspicious mass in the bladder or prostate, (2) nonsuspicious changes in the bladder, and (3) nondiagnostic exam. Descriptive statistics were used to report the clinical characteristics of the study cohort and the findings of cystoscopy. Univariate logistic regression analyses were used to identify predictors of malignant findings. RESULTS: The study cohort consisted of 69 patients (median age of 76 years). Initial cystoscopy findings were suspicious for malignancy in 26/69 patients (38%), nonsuspicious for malignancy in 34/69 patients (49%), and nondiagnostic in 9/69 patients (13%). The median follow-up time was 9 months (range 4-14 months). Twenty patients (29%) were diagnosed with malignancy (sensitivity of 75% and specificity of 78%). The procedure led to either diagnosis or treatment of 39 patients (57%). However, in 30 patients (43%), the initial cystoscopy did not aid in the diagnosis, led to misdiagnoses, or required a follow-up cystoscopy. On univariate analyses, none of the precystoscopy variables were predictive of bladder malignancy. CONCLUSION: Flexible cystoscopy in the setting of acute hematuria requiring hospitalization did not lead to diagnosis or treatment in over 40% of cases. In this setting, consideration should be given to performing an upfront cystoscopy under anesthesia.

Testicular microlithiasis defines a subgroup of azoospermic men with low rates of sperm retrieval.

OBJECTIVE: To investigate the prevalence of testicular microlithiasis and its association with sperm retrieval rates and histopathology in men with non-obstructive azoospermia. METHODS: A total of 120 men underwent scrotal ultrasonography prior to microsurgical testicular sperm extraction. Sperm retrieval rate, testicular histopathology, testicular size, reproductive hormones, karyotyping, Y chromosome microdeletion analyses, and presence of varicoceles and hydroceles were compared between men with and without testicular microlithiasis. RESULTS: The total sperm retrieval rate was 40%. Ten men with normal spermatogenesis were excluded. The remaining 110 men with non-obstructive azoospermia were analyzed and testicular microlithiasis was detected in 16 of them (14.5%). The sperm retrieval rate in that subgroup was only 6.2% (1/16) as opposed to 39.4% (37/94) in men with non-obstructive azoospermia and no evidence of microlithiasis (P = 0.009). The mean right and left testicular diameters were significantly lower in the microlithiasis group (P = 0.04). On multivariate logistic regression analysis, the presence of mictolithiasis (odds ratio 7.4, 95% confidence interval 2.3, 12.2; P = 0.01) was the only independent predictor of unsuccessful sperm retrieval. The 15 patients with microlithiasis and without successful sperm extraction were diagnosed by histopathology as having Sertoli cells only. The 16th patient with successful sperm retrieval had a histopathology of mixed atrophy and was diagnosed with Klinefelter syndrome. CONCLUSION: The presence of testicular microlithiasis is associated with low sperm retrieval rates among our cohort of men with non-obstructive azoospermia undergoing scrotal ultrasonography prior to microsurgical testicular sperm extraction. Larger, prospective studies should be conducted to confirm these findings.

Evolving biological associations of upfront cytoreductive nephrectomy in metastatic renal cell carcinoma.

BACKGROUND: Systemic responses to cytoreductive nephrectomy (CN) in the management of metastatic renal cell carcinoma (mRCC) are variable and difficult to anticipate. The authors aimed to determine the association of CN with modifiable International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk factors and oncological outcomes. METHODS: Consecutive patients with mRCC referred for potential CN (2009-2019) were reviewed. The primary outcome was overall survival (OS); variables of interest included undergoing CN and the baseline number of modifiable IMDC risk factors (anemia, hypercalcemia, neutrophilia, thrombocytosis, and reduced performance status). For operative cases, the authors evaluated the effects of IMDC risk factor dynamics, measured 6 weeks and 6 months after CN, on OS and postoperative treatment disposition. RESULTS: Of 245 treatment-naive patients with mRCC referred for CN, 177 (72%) proceeded to surgery. The CN cases had fewer modifiable IMDC risk factors (P = .003), including none in 71 of 177 patients (40.1%); fewer metastases (P = .011); and higher proportions of clear cell histology (P = .012). In a multivariable analysis, surgical selection, number of IMDC risk factors, metastatic focality, and histology were associated with OS. Total risk factors changed for 53.8% and 57.2% of the patients from the preoperative period to 6 weeks and 6 months after CN, respectively. Adjusted for preoperative IMDC risk scores, an increase in IMDC risk factors at 6 weeks and 6 months was associated with adverse OS (hazard ratio [HR], 1.57; 95% confidence interval [CI], 1.13-2.19; P = .007; HR, 2.52; 95% CI, 1.74-3.65; P < .001). CONCLUSIONS: IMDC risk factors are dynamic clinical variables that can improve after upfront CN in select patients, and this suggests a systemic benefit of cytoreduction, which may confer clinically meaningful prognostic implications.

A qualitative framework of non-selection factors for cytoreductive nephrectomy.

PURPOSE: Cytoreductive nephrectomy (CN) benefits a subset of patients with metastatic renal cell carcinoma (mRCC), however proper patient selection remains complex and controversial. We aim to characterize urologists' reasons for not undertaking a CN at a quaternary cancer center. METHODS: Consecutive patients with mRCC referred to MSKCC urologists for consideration of CN between 2009 and 2019 were included. Baseline clinicopathologic characteristics were used to compare patients selected or rejected for CN. The reasons cited for not operating and the alternative management strategies recommended were extrapolated. Using an iterative thematic analysis, a framework of reasons for rejecting CN was designed. Kaplan-Meier estimates tested for associations between the reasons for not undertaking a CN and overall survival (OS). RESULTS: Of 297 patients with biopsy-proven mRCC, 217 (73%) underwent CN and 80 (27%) did not. Median follow-up of patients alive at data cut-off was 27.3 months. Non-operative patients were older (p = 0.014), had more sites of metastases (p = 0.008), harbored non-clear cell histology (p = 0.014) and reduced performance status (p < 0.001). The framework comprised seven distinct themes for recommending non-operative management: two patient-fitness considerations and five oncological considerations. These considerations were associated with OS; four of the oncological factors conferred a median OS of less than 12 months (p < 0.001). CONCLUSION: We developed a framework of criteria by which patients were deemed unsuitable candidates for CN. These new insights provide a novel perspective on surgical selection, could potentially be applicable to other malignancies and possibly have prognostic implications.

Transcriptomic signatures related to the obesity paradox in patients with clear cell renal cell carcinoma: a cohort study.

BACKGROUND: Obesity is associated with an increased risk of developing clear cell renal cell carcinoma (RCC) but, paradoxically, obesity is also associated with improved oncological outcomes in this cancer. Because the biological mechanisms underlying this paradoxical association are poorly understood, we aimed to identify transcriptomic differences in primary tumour and peritumoral adipose tissue between obese patients and those at a normal weight. METHODS: In this cohort study, we assessed data from five independent clinical cohorts of patients with clear cell RCC aged 18 years and older. Overweight patients were excluded from each cohort for our analysis. We assessed patients from the COMPARZ phase 3 clinical trial, a cohort from the Cancer Genome Atlas (TCGA), and a Memorial Sloan Kettering (MSK) observational immunotherapy cohort for their inclusion into our study. We assessed overall survival in obese patients (those with a body-mass index [BMI] ≥30 kg/m2) and in patients with a normal weight (BMI 18·5-24·9 kg/m2, as per WHO's BMI categories), defined as the time from treatment initiation (in the COMPARZ and MSK immunotherapy cohorts) or surgery (in the TCGA cohort) to the date of any-cause death or of censoring on the day of the last follow-up. We also evaluated and validated transcriptomic differences in the primary tumours of obese patients compared with those of a normal weight. We compared gene-expression differences in peritumoral adipose tissue and tumour tissue in an additional, prospectively collected cohort of patients with non-metastatic clear cell RCC (the MSK peritumoral adipose tissue cohort). We analysed differences in gene expression between obese patients and those at a normal weight in the COMPARZ, TCGA, and peritumoral adipose tissue cohorts. We also assessed the tumour immune microenvironment in a prospective cohort of patients who had nephrectomy for localised RCC at MSK. FINDINGS: Of the 453 patients in the COMPARZ trial, 375 (83%) patients had available microarray data, pretreatment BMI measurements, and overall survival data for analyses, and we excluded 119 (26%) overweight patients, leaving a final cohort of 256 (68%) patients from this study for our analyses. From 332 patients in the TCGA cohort, we evaluated clinical and demographic data from 152 (46%) patients with advanced (ie, stages III and IV) clear cell RCC treated by nephrectomy; after exclusion of 59 (39%) overweight patients, our final cohort consisted of 93 (61%) patients. After exclusion of 74 (36%) overweight patients from the initial MSK immunotherapy study population of 203 participants, our final cohort for overall survival analysis comprised 129 (64%) participants. We found that overall survival was longer in obese patients than in those with normal weight in the TCGA cohort, after adjustment for stage or grade (adjusted HR 0·41, 95% CI 0·22-0·75), and in the COMPARZ clinical trial after adjustment for International Metastatic RCC Database (IMDC) risk score (0·68, 0·48-0·96). In the MSK immunotherapy cohort, the inverse association of BMI with mortality (HR 0·54, 95% CI 0·31-0·95) was not significant after adjustment for IMDC risk score (adjusted HR 0·72, 95% CI 0·40-1·30). Tumours of obese patients showed higher angiogenic scores on gene-set enrichment analysis-derived hallmark gene set angiogenesis signatures than did those of patients at a normal weight, but the degree of immune cell infiltration did not differ by BMI. We found increased peritumoral adipose tissue inflammation in obese patients relative to those at a normal weight, especially in peritumoral fat near the tumour. INTERPRETATION: We found aspects of the tumour microenvironment that vary by BMI in the tumour and peritumoral adipose tissue, which might contribute to the apparent survival advantage in obese patients with clear cell RCC compared with patients at a normal weight. The complex interplay between the clear cell RCC tumour and peritumoral adipose tissue microenvironment might have clinical relevance and warrants further investigation. FUNDING: Ruth L Kirschstein Research Service Award, American Society of Clinical Oncology Young Investigator Award, MSK's Ludwig Center, Weiss Family Kidney Research Fund, Novartis, The Sidney Kimmel Center for Prostate and Urologic Cancers, and the National Institutes of Health (National Cancer Institute) Cancer Center Support Grant.

Primary urethral cancer: treatment patterns and associated outcomes.

OBJECTIVES: To evaluate treatment patterns and associated outcomes of patients with urethral cancer. PATIENTS AND METHODS: After obtaining institutional review board approval we identified 165 patients treated for primary urethral cancer between 1956 and 2017. Treatment included monotherapy (surgery or radiation), dual therapy (surgery+radiation, surgery+chemotherapy, or chemotherapy+radiation) or triple therapy (surgery+radiation+chemotherapy). Rates of different treatments were described by treatment year. The association between treatment type and outcomes was evaluated with multivariable Cox regression models, adjusting for disease characteristics. RESULTS: The study cohort included 74 men and 91 women, with a median age of 61 years. Common histologies were squamous cell (36%), urothelial (27%) and adenocarcinoma (25%). At presentation, 72% of patients had invasive disease, 24% had nodal involvement, and 5% had metastases. Treatment included monotherapy (57%), dual therapy (21%), and triple therapy (10%). The use of monotherapy decreased over time, while rates of dual therapy remained consistent, and rates of triple therapy increased. The median follow-up was 4.7 years. Estimated 5-year local recurrence-free, disease-specific and overall survival were 51%, 48% and 41%, respectively. Monotherapy was associated with decreased local recurrence-free survival after adjusting for stage, histology, sex and year of treatment (P = 0.017). There was no evidence that treatment type was associated with distant recurrence, cancer-specific or overall survival. CONCLUSIONS: We found preliminary evidence that multimodal therapy, more commonly used in recent years, was of benefit in patients with primary urethral cancer. This finding should be confirmed in further studies involving multiple centres because of the low incidence of the disease.

Complication rate after cystectomy following pelvic radiotherapy: an international, multicenter, retrospective series of 682 cases.

PURPOSE: Conflicting evidence exists on the complication rates after cystectomy following previous radiation (pRTC) with only a few available series. We aim to assess the complication rate of pRTC for abdominal-pelvic malignancies. METHODS: Patients treated with radical cystectomy following any previous history of RT and with available information on complications for a minimum of 1 year were included. Univariable and multivariable logistic regression models were used to assess the relationship between the variable parameters and the risk of any complication. RESULTS: 682 patients underwent pRTC after a previous RT (80.5% EBRT) for prostate, bladder (BC), gynecological or other cancers in 49.1%, 27.4%, 9.8% and 12.9%, respectively. Overall, 512 (75.1%) had at least one post-surgical complication, classified as Clavien ≥ 3 in 29.6% and Clavien V in 2.9%. At least one surgical complication occurred in 350 (51.3%), including bowel leakage in 6.2% and ureteric stricture in 9.4%. A medical complication was observed in 359 (52.6%) patients, with UTI/pyelonephritis being the most common (19%), followed by renal failure (12%). The majority of patients (86%) received an incontinent urinary diversion. In multivariable analysis adjusted for age, gender and type of RT, patients treated with RT for bladder cancer had a 1.7 times increased relative risk of experiencing any complication after RC compared to those with RT for prostate cancer (p = 0.023). The type of diversion (continent vs non-continent) did not influence the risk of complications. CONCLUSION: pRTC carries a high rate of major complications that dramatically exceeds the rates reported in RT-naïve RCs.

Predictors of surgical site infection after radical cystectomy: should we enhance surgical antibiotic prophylaxis?

PURPOSE: To compare surgical site infections (SSI) rate after radical cystectomy (RC) over time and ascertain whether antibiotic prophylaxis should be enhanced. METHODS: All medical records of RC patients in a single tertiary uro-oncology center between 2007 and 2017 were analyzed. SSI was defined using the criteria of the US Centers for Disease Control and Prevention. All bacterial culture results and antimicrobial resistance rates were recorded. Lastly, multivariable logistic regression analysis was performed to ascertain SSI predictors. RESULTS: RC was performed in 405 patients, of which 96 (23.7%) developed SSI. No differences were demonstrated in the mean age, gender, NIDDM prevalence, neoadjuvant chemotherapy, positive preoperative urine culture, bowel preparation, and surgery time between both groups. However, statistically significant higher median BMI, age-adjusted Charlson Comorbidity score, usage of ceftriaxone preoperatively, and intensive care unit (ICU) hospitalization were noted in SSI patients. Overall, 62/96 (63.5%) SSI patients had a positive wound culture, with only 16.7% of the pathogens being sensitive to their perioperative antibiotics. Lastly, on multivariable analysis rising BMI, preoperative ceftriaxone and ICU hospitalization were associated with a higher SSI rate. CONCLUSIONS: Preoperative BMI reduction, and maximal preoperative medical optimization in an attempt to lower ICU admittance rates, should be part of the ideal strategy for lowering SSI rates. Additionally, preoperative antibiotics should be enhanced to harbor-wide spectrum coverage, based on local resistance rates.

The evolving role of cytoreductive nephrectomy: incorporating genomics of metastatic renal cell carcinoma into treatment decisions.

PURPOSE OF REVIEW: Recent publications evaluating cytoreductive nephrectomy in the era of targeted therapy emphasize the importance of patient selection. We reviewed the predictive role of genetic alterations in patients with metastatic renal cell carcinoma (mRCC) undergoing cytoreductive nephrectomy. RECENT FINDINGS: Studies evaluating the association between genetic alterations and outcomes following systemic treatment for mRCC include mainly patients after cytoreductive nephrectomy. Expression of proangiogenic genes, single nucleotide polymorphisms involving genes of the vascular-endothelial growth factor (VEGF) pathway and somatic mutations of chromatin remodeling genes were associated with response to VEGF-targeted therapy. Outcomes following treatment with mammalian target of rapamycin (mTOR) inhibitors were initially associated with mTOR/TSC1/TSC2 mutations; however, subsequent studies did not validate these findings but rather found an association between loss of PTEN expression and PBRM1 mutations and improved outcomes. Loss of PBRM1 was initially linked to response to immunotherapy; however, larger studies question this association and showed high expression of T-effector gene signature predicted improved outcome. Primary tumors with low intratumor heterogeneity but elevated somatic copy-number alterations were associated with rapid progression at multiple sites. SUMMARY: Genetic alterations may help select patients for cytoreductive nephrectomy and optimize timing of treatment. Intratumor heterogeneity and genetic discordance between primary and metastatic tumors may limit clinical applicability. Future studies should evaluate approaches to overcome these limitations.

Stone culture in patients undergoing percutaneous nephrolithotomy: a practical point of view.

INTRODUCTION: To determine the clinical yield of stone culture in patients undergoing percutaneous nephrolithotomy (PCNL), and to identify patients who may benefit from this test. MATERIALS AND METHODS: We queried our database for all patients who underwent PCNL from 2005 to 2017, from whom urine culture (UC) and stone culture (SC) were obtained. Study endpoint was systemic inflammatory response syndrome (SIRS) within 48 hours of PCNL. Risk factors for SIRS and for stone colonization with highly resistant pathogens were evaluated. Based on UC and SC results, we determined the proportion of patients in whom SC may alter the treatment, had SIRS occurred, with respect to the initial empiric treatment. RESULTS: The study group comprised of 512 patients with a median age of 53, of whom 323 (63%) were male. Positive UC were found in 137 (26.7%) patients, and positive SC in 117 (22.8%) patients. UC did not identify pathogens isolated from SC in 66 (12.8%) patients. Postoperative SIRS occurred in 50 (9.8%) patients. On multivariate analysis only SC was associated with postoperative SIRS. SC pathogens resistance rates ranged from 67% for treatment with 2nd generation cephalosporins to 9% for treatment with meropenem, and may alter the choice of antibiotics in 73 to 12 patients (14.2%-2.3% of the whole cohort), respectively. CONCLUSIONS: In similar and earlier studies, we found substantial discordance between SC and UC results, and an association between stone colonization and SIRS. However, the practical yield of this test varies with the type of antibiotic given, and is limited when broad spectrum antibiotic is used.

Clinical Implications of Stent Culture in Patients with Indwelling Ureteral Stents Prior to Ureteroscopy.

PURPOSE: We determined the ability of urine culture to predict stent culture status and associated infectious pathogens, and evaluated the association between stent culture and post-ureteroscopy sepsis. MATERIALS AND METHODS: We queried the prospectively collected database at our institution and identified all patients who underwent ureteroscopy between October 2010 and August 2016 who had a ureteral stent before the operation and from whom urine and stent cultures were obtained. The study end point was post-ureteroscopy sepsis within 48 hours of the procedure. We compared urine and stent culture findings, and performed univariate and multivariate analyses to identify predictors of post-ureteroscopy sepsis. RESULTS: The study group comprised 509 patients with a median age of 56 years, of whom 147 (28.9%) were female. Positive urine cultures were found in 91 patients (17.8%) and positive stent cultures were found in 104 (20.4%). Urine and stent cultures were positive in 48 patients (9.4%), of whom only 24 had identical bacteria in both cultures. The most common pathogens isolated from urine and stent cultures were Escherichia coli in 38.5% and Enterococcus in 18.4%. Sepsis developed in 25 patients (4.9%), including 21 (84%) with a positive stent culture and 14 (59%) with a positive urine culture. On multivariate analysis female gender and positive stent culture were significantly associated with post-ureteroscopy sepsis. CONCLUSIONS: Only half of the patients with ureteral stents prior to ureteroscopy, and positive stent and urine cultures had similar pathogens in both cultures. Female gender and positive stent culture were associated with a higher risk of post-ureteroscopy sepsis in this population. Stent culture may direct the proper antibiotic treatment in patients with sepsis after ureteroscopy.

Clinical Outcome of Patients with Fibrosis/Necrosis at Post-Chemotherapy Retroperitoneal Lymph Node Dissection for Advanced Germ Cell Tumors.

PURPOSE: Fibrosis accounts for approximately 50% of histological findings at post-chemotherapy retroperitoneal lymph node dissection, and is associated with reported relapse rates of 10% to 15%. We characterized patients with fibrosis at post-chemotherapy retroperitoneal lymph node dissection and identified predictors of adverse outcomes in this group. MATERIALS AND METHODS: We reviewed the medical records of men who underwent post-chemotherapy retroperitoneal lymph node dissection between 1989 and 2013 with histological findings of necrosis/fibrosis. With few exceptions post-chemotherapy retroperitoneal lymph node dissection after 1999 was performed with a bilateral template. Clinical, pathological and treatment related data were reported. Cox regression models were built to identify predictors of disease recurrence. RESULTS: The study cohort included 598 men with a median age of 32 years (IQR 25-38). Most cases (397 of 547, 73%) were classified as IGCCCG good risk, with no significant differences in risk classification before and after 1999 (p=0.55). Median followup was 7.3 years (IQR 3.2-12.3). The 5-year recurrence-free and overall survival rates were 94% and 96%, respectively. Overall 36 patients had disease recurrence, most of which was distant or outside the retroperitoneal lymph node dissection template. Procedures performed after 1999 and the presence of embryonal cell carcinoma on primary histology were associated with improved recurrence-free survival on multivariate analysis (p <0.01). CONCLUSIONS: Disease recurrence in patients with fibrosis at post-chemotherapy retroperitoneal lymph node dissection is an uncommon yet significant event, which is less likely to occur in patients treated after 1999 and in those with embryonal carcinoma on primary histology.