Expert Consensus on Pediatric Urodynamics Reporting Using Modified Delphi Technique.

PURPOSE: Urodynamic testing (UDS) is an important tool in the management of pediatric lower urinary tract conditions. There have been notable efforts to standardize pediatric UDS nomenclature and technique, but no formal guidelines exist on essential elements to include in a clinical report. We sought to identify ideal structure and elements of a pediatric UDS assessment based on expert consensus. MATERIALS AND METHODS: Pediatric urologists regularly performing UDS were queried using a Delphi process. Participants were invited representing varied geographic, experience, and societal involvement. Participants underwent 3 rounds of questionnaires between November 2022 and August 2023 focusing on report organization, elements, definitions, and automated electronic health record clinical decision support. Professional billing requirements were also considered. Consensus was defined as 80% agreeing either in favor of or against a topic. Elements without consensus were discussed in subsequent rounds. RESULTS: A diverse sample of 30 providers, representing 27 institutions across 21 US states; Washington, District of Columbia; and Canada completed the study. Participants reported interpreting an average number of 5 UDS reports per week (range 1-22). The finalized consensus report identifies 93 elements that should be included in a pediatric UDS report based on applicable study conditions and findings. CONCLUSIONS: This consensus report details the key elements and structure agreed upon by an expert panel of pediatric urologists. Further standardization of documentation should aid collaboration and research for patients undergoing UDS. Based on this information, development of a standardized UDS report template using electronic health record implementation principles is underway, which will be openly available for pediatric urologists.

Exercise capacity in people with haemophilia: A systematic review.

INTRODUCTION: Exercise capacity has been established as a protective factor against joint impairment in people with haemophilia (PWH). However, little is known about how exercise capacity is affected in PWH. AIM: To analyse exercise capacity, as assessed by standardised laboratory or field tests in PWH. METHODS: A systematic review was conducted to identify manuscripts investigating physical capacity in PWH. An electronic search of PubMed/MEDLINE, Embase, Web of Science, CENTRAL and CINAHL was conducted from inception to 13 April, 2022. Two independent reviewers performed data extraction and assessed study quality using the critical appraisal tools of the Joanna Briggs Institute. RESULTS: Nineteen studies with 825 patients were included. Most studies used the six-min walk test (6MWT) or peak/maximal oxygen consumption (VO2 max). In children, the distance walked ranged from 274 ± 36.02 to 680 ± 100 m. In adults, the distance walked ranged from 457.5 ± 96.9 to 650.9 ± 180.3 m. VO2 max ranged from 37 ± 8 to 47.42 ± 8.29 ml kg-1  min-1 . Most studies reported lower values of exercise capacity compared to standardised values. Overall, the quality of the studies was moderate. CONCLUSION: Most of the studies showed that PWH have lower exercise capacity compared to reference values of 6MWT or VO2 max. Based on these results, it is necessary to emphasise in both the promotion and the prescription of physical exercise in PWH.

Optimization of Pediatric Bowel Management Using an Antegrade Enema Troubleshooting Algorithm.

BACKGROUND: A successful flush is the ability to flush through the appendicostomy or cecostomy channel, empty the flush through the colon, and achieve fecal cleanliness. We evaluated our experience with patients who were having flush difficulties based on a designed algorithm. METHODS: Eight patients with flush difficulties were initially evaluated. Based on the need for additional surgery versus changes in bowel management therapy (BMT), we developed an algorithm to guide future management. The algorithm divided flush issues into before, during, and after flushing. Children aged <20 y who presented with flush issues from September 2018 to August 2019 were evaluated to determine our algorithm's efficacy. Specific outcomes analyzed included changes in BMT versus need for additional surgery. RESULTS: After algorithm creation, 29 patients were evaluated for flush issues. The median age was 8.4 y (interquartile range: 6, 14); 66% (n = 19) were men. Underlying diagnoses included anorectal malformations (n = 17), functional constipation (n = 7), Hirschsprung's disease (n = 2), spina bifida (n = 2), and prune belly (n = 1). A total of 35 flush issues/complaints were noted: 29% before the flush, 9% during the flush, and 63% after the flush. Eighty percent of issues before the flush required surgical intervention, wherease 92% of issues during or after the flush were managed with changes in BMT. CONCLUSIONS: Most flush issues respond to changes in BMT. This algorithm can help delineate which types of flush issues would benefit from surgical intervention and what problems might be present if patients are not responding to changes in their flush regimen.

Doxorubicin induces detrusor smooth muscle impairments through myosin dysregulation, leading to a risk of lower urinary tract dysfunction.

Cytotoxic chemotherapy is the foundation for the treatment of the wide variety of childhood malignancies; however, these therapies are known to have a variety of deleterious side effects. One common chemotherapy used in children, doxorubicin (DOX), is well known to cause cardiotoxicity and cardiomyopathy. Recent studies have revealed that DOX impairs skeletal and smooth muscle function and contributes to fatigue and abnormal intestinal motility in patients. In this study, we tested the hypothesis that systemic DOX administration also affects detrusor smooth muscle (DSM) function in the urinary bladder, especially when administered at a young age. The effects on the DSM and bladder function were assessed in BALB/cJ mice that received six weekly intravenous injections of DOX (3 mg·kg-1·wk-1) or saline for the control group. Systemic DOX administration resulted in DSM hypertrophy, increased voiding frequency, and a significant attenuation of DSM contractility, followed by a slower relaxation compared with the control group. Gene expression analyses revealed that unlike DOX-induced cardiotoxicity, the bladders from DOX-administered animals showed no changes in oxidative stress markers; instead, downregulation of large-conductance Ca2+-activated K+ channels and altered expression of myosin light-chain kinase coincided with reduced myosin light-chain phosphorylation. These results indicate that in vivo DOX exposure caused DSM dysfunction by dysregulation of molecules involved in the detrusor contractile-relaxation mechanisms. Collectively, our findings suggest that survivors of childhood cancer treated with DOX may be at increased risk of bladder dysfunction and benefit from followup surveillance of bladder function.

Altered detrusor contractility and voiding patterns in mice lacking the mechanosensitive TREK-1 channel.

BACKGROUND: Previously published results from our laboratory identified a mechano-gated two-pore domain potassium channel, TREK-1, as a main mechanosensor in the smooth muscle of the human urinary bladder. One of the limitations of in vitro experiments on isolated human detrusor included inability to evaluate in vivo effects of TREK-1 on voiding function, as the channel is also expressed in the nervous system, and may modulate micturition via neural pathways. Therefore, in the present study, we aimed to assess the role of TREK-1 channel in bladder function and voiding patterns in vivo by using TREK-1 knockout (KO) mice. METHODS: Adult C57BL/6 J wild-type (WT, N = 32) and TREK-1 KO (N = 33) mice were used in this study. The overall phenotype and bladder function were evaluated by gene and protein expression of TREK-1 channel, in vitro contractile experiments using detrusor strips in response to stretch and pharmacological stimuli, and cystometry in unanesthetized animals. RESULTS: TREK-1 KO animals had an elevated basal muscle tone and enhanced spontaneous activity in the detrusor without detectable changes in bladder morphology/histology. Stretch applied to isolated detrusor strips increased the amplitude of spontaneous contractions by 109% in the TREK-1 KO group in contrast to a 61% increase in WT mice (p ≤ 0.05 to respective baseline for each group). The detrusor strips from TREK-1 KO mice also generated more contractile force in response to electric field stimulation and high potassium concentration in comparison to WT group (p ≤ 0.05 for both tests). However, cystometric recordings from TREK-1 KO mice revealed a significant increase in the duration of the intermicturition interval, enhanced bladder capacity and increased number of non-voiding contractions in comparison to WT mice. CONCLUSIONS: Our results provide evidence that global down-regulation of TREK-1 channels has dual effects on detrusor contractility and micturition patterns in vivo. The observed differences are likely due to expression of TREK-1 channel not only in detrusor myocytes but also in afferent and efferent neural pathways involved in regulation of micturition which may underly the "mixed" voiding phenotype in TREK-1 KO mice.

Inpatient interventions that may preclude outpatient open pyeloplasty in infants.

OBJECTIVE: In the majority of published series, children undergoing open pyeloplasty are admitted for at least one night. We hypothesized that it would be possible in the majority of infants to perform open pyeloplasty as an outpatient procedure. MATERIALS AND METHODS: All patients who underwent open pyeloplasty by a single surgeon between 2008 and 2016 were retrospectively reviewed. Demographic data (age at surgery, gender, pre- and postoperative imaging studies, laterality, type of local anesthesia), operative time, duration of hospital stay, need for narcotic analgesics, complications, readmission within 1-month after surgery and need for additional procedures were abstracted. RESULTS: A total of 18 infants underwent open pyeloplasty by single surgeon. Mean age at time of surgery was 19 months (range 3-23 months). There were 8 girls and 10 boys. In addition to general anesthesia, all of the patients received regional anesthesia (caudal block 8, epidural block 8, subcutaneous nerve block 2). Median operative time was 135 minutes (range 81-166). Median hospital stay was 1 day (range 1 to 2). Two patients required iv narcotics for pain management. None of the patients required parenteral administration of other medications during the short hospitalization. No patients required any additional procedures or hospital readmissions within 1 month from surgery. CONCLUSIONS: In appropriately selected patients, outpatient pyeloplasty appears to be feasible with an oral postoperative analgesia plan to be administered at home.

Initial Imaging for Pediatric Renal Tumors: An Opportunity for Improvement.

PURPOSE: Current Children's Oncology Group studies on renal malignancy focus on minimizing treatment side effects with a goal of decreasing long-term complications. In this series we evaluate the patterns of initial imaging in children with renal tumors. MATERIALS AND METHODS: We retrospectively reviewed records of 122 patients treated for renal tumors at our institution between 2005 and 2016. Ideal imaging was defined as cross-sectional imaging of the chest, abdomen and pelvis in a single setting without any additional ionizing radiation exposing scans. RESULTS: Median patient age was 33.5 months (range 1 to 195). A total of 101 patients (83%) were initially evaluated elsewhere and subsequently referred to oncology (67.2%) for further evaluation. Before treatment 58 patients (47.5%) underwent imaging that was obtained in an ideal manner. Compared to those undergoing ideal imaging, median additional radiation exposure was 2.31 mSv (range 0.9 to 11.5), 3.08 mSv (0.6 to 11.7) and 5.1 mSv (1.2 to 16) in patients younger than 5 years, 5 to 9 years old and 10 years or older, respectively. Factors associated with undergoing ideal imaging included undergoing abdominal ultrasound as an initial scan (OR 3.637, p = 0.001), while presentation to an emergency department resulted in a reduced likelihood of undergoing ideal imaging (OR 0.351, p = 0.012). Factors associated with a decreased likelihood of undergoing initial screening ultrasound included presenting with vague symptoms (OR 0.072, p = 0.045) and presenting to a tertiary care emergency department (OR 0.228, p = 0.027). CONCLUSIONS: Current patterns of initial imaging for pediatric renal tumors are often associated with unnecessary and avoidable imaging studies, resulting in increased radiation exposure. Presenting to the emergency room as the initial point of contact with vague symptoms is associated with a decreased likelihood of undergoing appropriate or ideal pretherapy imaging, while initial evaluation with ultrasound is associated with a greater likelihood of undergoing ideal imaging, reducing overall radiation exposure. We advocate initial abdominal ultrasound in all pediatric patients suspected of having an abdominal mass. Our data highlight an opportunity for quality improvement across specialties caring for children with renal tumors.

Can a Modified Bosniak Classification System Risk Stratify Pediatric Cystic Renal Masses?

PURPOSE: We characterize and apply the modified Bosniak classification system to a cohort of children with cystic renal lesions and known surgical pathology. MATERIALS AND METHODS: We identified all patients at our institution with cystic renal masses who also underwent surgery for these lesions. Patients without available preoperative imaging or pathology were excluded. All radiological imaging was independently reviewed by a pediatric radiologist blinded to pathological findings. Imaging characteristics (size, border, septations, calcifications, solid components, vascularity) were recorded from the most recent preoperative ultrasounds and computerized tomograms. The modified Bosniak classification system was applied to these scans and then correlated with final pathology. RESULTS: A total of 22 patients met study criteria. Median age at surgery was 6.1 years (range 11 months to 16.8 years). Of the patients 12 (54.5%) underwent open nephrectomy, 6 (27.3%) open partial nephrectomy, 2 (9.1%) laparoscopic cyst decortication, 1 (4.5%) open renal biopsy and 1 (4.5%) laparoscopic partial nephrectomy. Final pathology was benign in 9 cases (41%), intermediate in 6 (27%) and malignant in 7 (32%). All malignant lesions were modified Bosniak class 4, all intermediate lesions were modified class 3 or 4 and 8 of 9 benign lesions (89%) were modified class 1 or 2. CONCLUSIONS: Cystic renal lesions in children with a modified Bosniak class of 1 or 2 were most often benign, while class 3 or 4 lesions warranted surgical excision since more than 90% of masses harbored intermediate or malignant pathology. The modified Bosniak classification system appears to allow for a reasonable clinical risk stratification of pediatric cystic renal masses.

Patients with disorders of sex development and proximal hypospadias are at high risk for reoperation.

PURPOSE: Surgical repair for proximal hypospadias has been associated with long-term success rates of 32-68%. In a prior study, outcomes for proximal hypospadias in patients with a diagnosis of disorders of sex development (DSD) were no different than those of patients without DSD. The objective of our study is to report our experience with proximal hypospadias repair in patients with and without DSD. METHODS: We retrospectively reviewed patients who underwent repair of proximal hypospadias between 2005 and 2016. Data collected included patient and disease characteristics, operative details, complications, and follow-up. The primary outcome was unplanned reoperation. RESULTS: Sixty seven patients were identified; 30 (44.8%) with DSD and 37 (55.2%) without DSD. Median follow-up was 28.3 months (IQR 18.9-45.7). 41 patients (61.2%) underwent at least one unplanned reoperation, median time to unplanned reoperation 10.3 months. More patients with DSD needed an unplanned reoperation (80 vs. 45.9%, p = 0.024). During the first 12 months after initial repair, there was no difference in unplanned reoperation rates (40 vs. 32.4%, p = 0.611), but there was a difference in the first 24 months post-operatively (76.7 vs. 43.2%, p = 0.007). On multivariate logistic regression, older age at initial repair (OR 1.144) and two stage repair (OR 7.644) were positively associated with unplanned reoperation in the first 2 years after repair. CONCLUSIONS: Proximal hypospadias repair is associated with an overall 61.2% reoperation rate regardless of associated DSD diagnosis. Patients with DSD are more likely to undergo an unplanned reoperation in the first 2 years after repair.

Preventative effects of a HIF inhibitor, 17-DMAG, on partial bladder outlet obstruction-induced bladder dysfunction.

Posterior urethral valves are the most common cause of partial bladder outlet obstruction (PBOO) in the pediatric population. Pathological changes in the bladder developed during PBOO are responsible for long-lasting voiding dysfunction in this population despite early surgical interventions. Increasing evidence showed PBOO induces an upregulation of hypoxia-inducible factors (HIFs) and their transcriptional target genes, and they play a role in pathophysiological changes in the obstructed bladders. We hypothesized that blocking HIF pathways can prevent PBOO-induced bladder dysfunction. PBOO was surgically created by ligation of the bladder neck in male C57BL/6J mice for 2 wk. PBOO mice received intraperitoneal injection of either saline or 17-DMAG (alvespimycin, 3 mg/kg) every 48 h starting from day 1 postsurgery. Sham-operated animals received injection of saline on the same schedule as PBOO mice and served as controls. The bladders were harvested after 2 wk, and basal activity and evoked contractility of the detrusor smooth muscle (DSM) were evaluated in vitro. Bladder function was assessed in vivo by void spot assay and cystometry in conscious, unrestrained mice. Results indicated the 17-DMAG treatment preserved DSM contractility and partially prevented the development of detrusor over activity in obstructed bladders. In addition, PBOO caused a significant increase in the frequency of micturition, which was significantly reduced by 17-DMAG treatment. The 17-DMAG treatment improved urodynamic parameters, including increases in the bladder pressure at micturition and nonvoid contractions observed in PBOO mice. These results demonstrate that treatment with 17-DMAG, a HIF inhibitor, significantly alleviated PBOO-induced bladder pathology in vivo.

Reliability of intraoperative frozen section for the diagnosis of renal tumors suspicious for malignancy in children and adolescents.

BACKGROUND: The ability of intraoperative frozen section (IFS) to reliably diagnose renal tumors in children and adolescents is largely unknown. The objective of our study is to evaluate the ability of IFS to establish a histologic diagnosis for renal tumors in this population. METHODS: We reviewed our experience with patients who underwent IFS at the time of surgery for a renal tumor suspicious for malignancy from 2005 to 2015. The IFS was compared to the final pathology (FP). Data on concordance and reliability were analyzed. RESULTS: One hundred thirty patients underwent surgical interventions for a renal tumor suspicious for malignancy, and 32 (25%) patients underwent IFS. Median turnaround time for IFS was 20 min (range 13-44). The histologic IFS diagnosis correlated with FP in 26 (81.2%) cases was discrepant in three (9.4%) cases, and IFS was deferred to FP in three (9.4%) cases (kappa 0.71, 95% confidence interval [CI]: 0.52-0.899, P < 0.001). The IFS correctly distinguished between Wilms tumor and non-Wilms tumor in 30 (94%) cases (kappa 0.874, 95% CI: 0.705-1, P < 0.001). A total of 17 of 19 (89.5%) Wilms tumors were correctly diagnosed by IFS, yielding a sensitivity of 0.89 (95% CI: 0.67-0.99) and a specificity of 1 (95% CI: 0.75-1). CONCLUSION: IFS is a reliable tool to establish a histologic diagnosis and to differentiate between Wilms and non-Wilms tumors in children and adolescents with renal tumors. The use of IFS should be encouraged in cases in which obtaining a diagnosis will provide guidance for important "real-time" medical decision making, specifically additional adjunctive surgical procedures.

Managing adult urinary incontinence from the congenitally incompetent bladder outlet.

PURPOSE OF REVIEW: Treatment of urinary incontinence in adult patients with congenital incompetent bladder outlet (exstrophy-epispadias complex, cloacal anomalies, or neurogenic bladder secondary to myelomeningocele) is a challenging surgical problem. In this review article, we summarize and highlight recent studies in the management of incontinence in this patient population. RECENT FINDINGS: The literature regarding management of urinary incontinence in this patient population is scarce. Injection of bulking agents to the bladder neck, artificial/autologous slings, artificial urinary sphincters, bladder neck reconstruction, bladder neck closure, or a combination of these are the cornerstone of management. Augmentation cystoplasty is a major adjunct procedure that can help increase continence rate and success of surgery in select patients. The level of evidence on bladder neck procedures for this patient population is low because of significant limitations, including small sample, heterogeneity of primary diagnosis/surgical techniques, variable definitions of continence, and the retrospective nature of most studies in this field. SUMMARY: Standard options for treatment of urinary incontinence in the congenitally incompetent bladder outlet procedure remain unchanged. There is no single reproducible procedure to accomplish the goal of renal preservation and continence in these patients, and often patients require multiple procedures to achieve continence. Most importantly, the pediatric and adult urologist should continue to work toward achieving a well tolerated and efficient transition of care. There is a need to standardize data acquisition and reporting of outcomes. Although randomized control studies would be ideal, because of the small number of patients with these conditions, this may not be practical. Collaboration and continued discussion among experts in the field is needed to gain a better understanding of the optimal management strategy in this growing patient population.

Buckshot colic: utilizing holmium:yag laser for ureteroscopic removal of a bullet fragment within the proximal ureter.

Buckshot colic is a rare phenomenon, presenting as firearm-induced urinary tract obstruction. We present a case of gunshot-induced ureteral obstruction in a 49-year-old male, treated endoscopically with the holmium:YAG (holmium) laser. CT revealed a 1 cm bullet fragment within the left proximal ureter. A percutaneous nephrolithotomy was performed utilizing the holmium laser to fragment the metal into basket-retrievable pieces. At 4 month follow up the patient is without evidence of stricture. To our knowledge, this is the first reported utilization of the holmium laser to treat "buckshot colic". Endoscopy with holmium laser appears a feasible and safe treatment option.

Mortality after radical cystectomy: impact of obesity versus adiposity after adjusting for skeletal muscle wasting.

PURPOSE: We assess the impact of obesity, as measured conventionally by body mass index vs excess adiposity as measured by fat mass index, on mortality after radical cystectomy for bladder cancer, adjusting for the presence of skeletal muscle wasting. MATERIALS AND METHODS: This retrospective cohort study included 262 patients treated with radical cystectomy for bladder cancer between 2000 and 2008 at the Mayo Clinic. Lumbar skeletal muscle and adipose compartment areas were measured on preoperative imaging. Overall survival was compared according to gender specific consensus fat mass index and skeletal muscle index thresholds as well as conventional body mass index based criteria. Predictors of all cause mortality were assessed by multivariable modeling. RESULTS: Increasing body mass index correlated with improved overall survival (p=0.03) while fat mass index based obesity did not (p=0.08). After stratification by sarcopenia, no obesity related 5-year overall survival benefit was observed (68% vs 51.4%, p=0.2 obese vs normal and 40% vs 37.4%, p=0.7 sarcopenia vs sarcopenic/obese). On multivariable analysis class I obesity according to body mass index (HR 0.79, p=0.33) or fat mass index criteria (HR 0.85, p=0.45) was not independently associated with all cause mortality after adjusting for sarcopenia (HR 1.7, p=0.01) as well as age, performance status, pTN stage and smoking status. However, in patients with normal lean muscle mass each 1 kg/m(2) increase in weight or adipose mass was associated with a 7% to 14% decrease in all cause mortality. CONCLUSIONS: After adjusting for lean muscle wasting, neither measurements of obesity nor adiposity were significantly associated with all cause mortality in patients treated with radical cystectomy, although subanalyses suggest a potential benefit among those with normal lean muscle mass.

Sarcopenia in patients with bladder cancer undergoing radical cystectomy: impact on cancer-specific and all-cause mortality.

BACKGROUND: The authors evaluated sarcopenia as a predictor of cancer-specific survival (CSS) and overall survival (OS) among patients with urothelial cancer of the bladder undergoing radical cystectomy (RC). METHODS: The lumbar skeletal muscle index (SMI) of 205 patients treated with RC for urothelial cancer between 2000 and 2007 was measured. Sarcopenia was classified according to international consensus definitions (SMI of < 55 cm(2)/m(2) for men and < 39 cm(2)/m(2) for women). The CSS and OS were estimated using the Kaplan-Meier method and compared with the log-rank test. Variables associated with CSS and all-cause mortality were summarized with hazard ratios (HRs). RESULTS: Of 205 patients, 141 (68.8%) were sarcopenic. Patients with sarcopenia were older, but were otherwise similar to patients without sarcopenia with respect to sex, Charlson comorbidity index, American Society of Anesthesiologists score, Eastern Cooperative Oncology Group performance status, receipt of neoadjuvant chemotherapy, TNM stage of disease, and tumor grade (P > .05 for all). The median follow-up was 6.7 years, during which time 135 patients died, including 91 who died of bladder cancer. Sarcopenic patients had significantly worse 5-year CSS (49% vs 72%; P = .003) and OS (39% vs 70%; P = .003) compared with patients without sarcopenia. Moreover, sarcopenia was found to be independently associated with both increased CSS (HR, 2.14; P = .007) and all-cause mortality (HR, 1.93; P = .004) on multivariable analysis. CONCLUSIONS: The presence of sarcopenia was found to significantly increase a patient's risk of CSS and all-cause mortality after undergoing RC for bladder cancer.

Positive vascular wall margins have minimal impact on cancer outcomes in patients with non-metastatic renal cell carcinoma (RCC) with tumour thrombus.

OBJECTIVE: To evaluate the impact of microscopically positive vascular margins on recurrence and cancer-specific survival (CSS) in patients with renal cell carcinoma (RCC) with venous thrombus PATIENTS AND METHODS: We reviewed the records from the period 1993 to 2009 of consecutive patients treated surgically for RCC with venous tumour thrombus at the University of Texas MD Anderson Cancer Center. Patients with metastatic disease, positive soft tissue margins or gross residual disease at time of thrombectomy were excluded. The primary outcome measures were local or systemic disease recurrence, and CSS. Univariate and multivariate analysis were used to evaluate whether microscopically positive vascular margins were associated with RCC recurrence or CSS after nephrectomy with thrombectomy. RESULTS: A total of 256 patients with RCC were identified with a median (interquartile range) follow-up of 36.7 (18.4-63.5) months. Microscopic tumour was present at the margin of resection in 47 patients (18.4%). The median recurrence-free interval was significantly shorter in patients with positive vascular margins: 22.1 vs 70.2 months (P = 0.009). The rate of local recurrence was higher in patients with positive vein margins: 12.8 vs 4.3% (P < 0.01). Local recurrence without concomitant systemic recurrence was identified in only two of 256 (0.8%) patients. Patients with positive vascular margins had significantly worse CSS times compared with patients with negative vascular margins: 37.7 vs 93.0 months (P = 0.004). In multivariable analysis, positive vascular margins were found to be independently predictive of local recurrence but not of systemic recurrence or CSS. CONCLUSIONS: Complete surgical excision should always be attempted because positive vascular wall margins increase local recurrence rates. Invasion of RCC into the vein wall at the resection margin is associated with aggressive tumour biology, and the majority of patients with positive vascular wall margins experience systemic recurrence.

The impact of histology on survival for patients with metastatic renal cell carcinoma undergoing cytoreductive nephrectomy.

OBJECTIVE: To evaluate the impact of histology on cancer-specific and overall survival for patients with metastatic renal cell carcinoma (mRCC) undergoing cytoreductive nephrectomy (CN). MATERIALS AND METHODS: We retrospectively reviewed the data of 505 patients with mRCC who underwent CN at Mayo Clinic, Rochester, MN, USA, between 1970 and 2008. All specimen were re-reviewed by a single genitourinary pathologist. Survival was estimated using the Kaplan-Meier method and compared according to histology with the log-rank test. Cox proportional hazard regression models were used to evaluate the association of histology with outcome. RESULTS: Forty (8%) patients with non-clear cell histology and 465 (92%) patients with clear cell histology were identified. The median follow-up was 7.8 years. Metastatic non-clear cell histology was associated with a significantly older median age at nephrectomy (66 vs. 60 years; P = 0.002), larger median tumor size (11.5 vs. 9.2 cm; P = 0.02), and higher rate of lymph node involvement (50% vs. 16%; P < 0.001). No significant difference in 3-year cancer-specific survival (25% vs. 22%; P = 0.50) was noted between patients with clear cell and non-clear cell histology. On multivariate analysis, non-clear cell histology was not significantly associated with patients' risk of death from cancer (HR 0.96; 95% CI 0.61, 1.51; P = 0.85). CONCLUSIONS: Non-clear cell histology was not independently associated with adverse survival for patients with mRCC undergoing CN. As such, we advocate that surgical resection should continue to be considered in the multimodal treatment approach to these patients, while additional efforts to risk stratify and optimize management in this setting remain necessary.