Factors related to lymph node sampling at the time of surgery in children, adolescents, and young adults with unilateral non-metastatic renal cell carcinoma.

INTRODUCTION: Renal cell carcinoma (RCC) is rare in the pediatric, adolescent, and young adult (PAYA) population. PAYA patients with RCC have a high rate of lymph node (LN) involvement, regardless of primary tumor size, yet data to guide surgical LN management in this group are limited. OBJECTIVE: The objective of this study was to determine what factors are associated with LN sampling (protocol adherence) in PAYAs with RCC. METHODS: The National Cancer Database (NCDB) between 2004 and 2013 was queried for patients aged ≤30 yrs with non-metastatic, unilateral RCC managed with surgery. Logistic regression analyses were performed to evaluate factors associated with LN sampling. RESULTS: A total of 2857 patients met study criteria. Pathologically, 2510 (87.8%) patients were Nx, 278 (9.7%) N0, and 69 (2.4%) N1. Older age was associated with omission of LN sampling (odds ration [OR]: 1.065, 95% confidence interval [CI]: 1.04-1.1, P < 0.001). Higher institutional volume (OR: 0.971, 95% CI: 0.96-0.99, P < 0.001), stage 3 tumors (OR: 0.19, 95% CI: 0.11-0.33, P < 0.001), pre-operative clinical node involvement (OR: 0.32, 95% CI: 0.12-0.86, P = 0.024), tumor size >10 cm (OR: 0.27, 95% CI: 0.12-0.57, P = 0.001), and radical nephrectomy (OR: 0.245, 95% CI: 0.16-0.38, P < 0.001) were associated with patients undergoing LN sampling. DISCUSSION: Lymph node sampling is performed in <15% of PAYA patients with RCC. Given the higher rate of translocation RCC pathology in younger patients, which leads to a higher prevalence of nodal involvement (especially with small masses), and the subsequent need for aggressive surgical control of disease, LN sampling and protocol adherence are potentially underutilized in this population and may present a unique opportunity for urologists to improve the care of PAYAs. Data from administrative databases are helpful for rare diseases such as PAYA RCC, but comes with limitations such as missing data. There are several factors that could contribute to LN sampling utilization (National comprehensive cancer network (NCCN) or Children's Oncology Group institution designation, surgeon experience, annual volume, specialty, operative approach, etc.) that cannot be further examined using the NCDB. CONCLUSION: Pediatric, adolescent, and young adult patients with localized RCC are less likely to undergo surgical LN sampling if they are older, have tumors <10 cm or of less advanced stage, have no pre-operative clinical suspicion of LN involvement, are treated with partial nephrectomy, or are treated at lower volume centers. It appears that approaches from adults with RCC are being applied to PAYAs despite evidence that PAYAs with RCC experience a significant rate of LN involvement even with small tumors.

Appropriateness for testis-sparing surgery based on the testicular tumor size in a pediatric and adolescent population.

INTRODUCTION: In children, most small testicular tumors are benign, and testicular-sparing surgery (TSS) is a viable treatment option. OBJECTIVE: The objective of this study is to assess for correlation between the tumor size and final pathologic diagnoses appropriate for TSS for pediatric and adolescent patients with an intratesticular mass and negative serum tumor markers (STMs). MATERIALS AND METHODS: A retrospective review of 24 patients (aged 0-18 years) who underwent radical or partial orchiectomy between 2003 and 2015. Patients with unifocal, unilateral intratesticular tumors and negative STMs were included. Tumors with benign and non-germ cell histology were considered appropriate for TSS, and active germ cell tumor elements on final histology were categorized as inappropriate for TSS. Baseline characteristics, tumor size, and frozen section results were evaluated for association, for the entire cohort and then for a subset of pubertal and postpubertal patients (defined as ≥10 years old). RESULTS: Patients with testicular tumor pathology inappropriate for TSS were significantly older (median age 17.1 years, P = 0.03). A 2-cm size cutoff did not accurately predict pathology for the entire cohort, or for just pubertal and postpubertal patients (P = 0.132, P = 0.154, respectively). Frozen section and final pathology demonstrated good agreement (κ = 0.826, P < 0.001) as did pre-operative and final pathologic size measurement (κ = 0.703, P < 0.001). Frozen section analysis did not miss a TSS inappropriate pathology. DISCUSSION: The present data refute the finding in adults that a 2-cm cutoff accurately predicts pathology in pediatric patients with an intratesticular mass and normal STMs. These data suggest that TSS should still be offered, regardless of the tumor size alone, but frozen section appears to more accurately predict pathology than the tumor size, and its use should, thus, be emphasized. There are several limitations of this study to mention. First, this is a retrospective review of a small cohort of patients with a rare clinical scenario, which necessitated the combination of pediatric and adolescent patients. The study did not evaluate oncologic outcomes. CONCLUSIONS: In children with an intratesticular tumor and normal STMs, a tumor size cutoff of 2 cm does not appear to accurately predict the final pathology. However, the data presented support the continued use intra-operative frozen section analysis in both children and adolescents undergoing TSS.

Development of a postoperative care pathway for children with renal tumors.

PURPOSE: To identify the factors associated with a shorter postoperative stay, as an initial step to develop a care pathway for children undergoing extirpative kidney surgery. STUDY DESIGN: This study retrospectively reviewed patients managed with upfront open radical nephrectomy for renal tumors between 2005 and 2016 at a pediatric tertiary care facility. Univariate and multivariate logistic regression were performed to identify factors associated with early discharge (by postoperative day 4). RESULTS: A total of 84 patients met inclusion criteria. Median age was 28.1 months (range 1.8-193.1). Thirty-four (40.5%) patients had a nasogastric tube postoperatively. The patients were advanced to a clear liquid diet on a median postoperative day 2 (range 0-7) and regular diet on a median postoperative day 3 (range 1-8). Median time from surgery to discharge was 5 days (range 2-12), with 38 (45.2%) discharged early. Univariate and multivariate logistic regression analyses showed that earlier resumption of regular diet (OR 0.523, P = 0.028) was positively associated with early discharge. Other analyzed factors were not significant (see Table). DISCUSSION: Timely initiation of adjuvant therapy is a specific requirement of Children's Oncology Group (COG) protocols. Chemotherapy and radiation therapy are ideally initiated simultaneously, as early as possible, within 2 weeks of surgery. Thus, factors that can facilitate early discharge from the hospital can maximize protocol adherence with respect to timing of adjuvant therapy initiation and optimize patient outcome. This study shed light on several postoperative factors and how these relate to postoperative stay and recovery. Specifically, tumor size, pre-operative bowel preparation, extent of lymph node sampling, stage, operative time, estimated blood loss, surgical service, postoperative nasogastric tube use, transfusion, and chemotherapy prior to discharge were not associated with discharge timing. Early re-feeding was associated with early discharge. Thus, it seems reasonable that, when developing a postoperative care pathway for these patients, these factors be considered and specifically encourage early re-feeding. In pediatrics, data on early recovery after surgery protocols are limited, and high-quality studies are unavailable. Within pediatric urology, early recovery after surgery protocols in children undergoing major urologic reconstruction have been shown to reduce hospital stay and can decrease complication rates. It seems reasonable that a similar pathway can be applied to children undergoing radical nephrectomy for suspected malignancy. CONCLUSIONS: For children with renal tumors who underwent radical nephrectomy, early re-feeding was associated with a shorter time to discharge. Use of bowel preparation and nasogastric tube did not appear to shorten time to discharge. These data are important for developing postoperative care pathways for these patients.

Patterns of lymph node sampling and the impact of lymph node density in favorable histology Wilms tumor: An analysis of the national cancer database.

INTRODUCTION: There is controversy about the role of lymph node (LN) sampling or dissection in the management of favorable histology (FH) Wilms tumor (WT), specifically how it performed and how it may impact survival. OBJECTIVE: The objective of this study was to analyze factors affecting LN sampling patterns and the impact of LN yield and density (number of positive LNs/LNs examined) on overall survival (OS) in patients with advanced-stage favorable histology Wilms tumor (FHWT). METHODS: The National Cancer Database (NCDB) was queried for patients with FHWT during 2004-2013. Demographic, clinical and OS data were abstracted for those who underwent surgical resection. Poisson regression was performed to analyze how factors influenced LN yield. Patients with positive LNs had LN density calculated and were further analyzed. RESULTS: A total of 2340 patients met criteria, with a median age at diagnosis of 3 years (range 0-78 years). The median number of LNs examined was three (range 0-87). Lymph node yield was affected by age, race, insurance, tumor size, laterality, advanced stage, LN positivity, and institutional volume. A total of 390 (16.6%) patients had LN-positive disease. Median LN density for these LN-positive patients was 0.38 (range 0.02-1) (Summary Figure). Estimated 5-year OS was significantly improved for those with LN density ≤0.38 vs. >0.38 (94% vs. 84.6%, P = 0.012). In this population, on multivariate analysis, age and LN density were significant predictors of OS. DISCUSSION: It is difficult to compile large numbers of cases in rare diseases like WT, and fortunately a large administrative database such as the NCDB can serve as a great resource. However, administrative data come with inherent limitations such as missing data and inability to account for a variety of factors that may influence LN yield and/or OS (specimen designation, pathologist experience, surgeon experience/volume, institutional Children's Oncology Group (COG) association, etc.). In this specific disease, the American Joint Committee on Cancer staging (captured by the NCDB) is different than the COG WT staging system that is used clinically, and the NCDB does not capture oncologic outcomes beyond OS. CONCLUSIONS: In a review of the NCDB, various factors associated with LN yield and observed LN density were identified to be significantly associated with OS in patients with LN-positive FHWT. This reinforces the need for adequate LN sampling at the time of WT surgery, to maximize surgical disease control. It was proposed that LN density as a metric may allow for improved risk-stratification, and possibly allow for therapeutic reduction in a sub-set of patients with low LN density.

Utility of retrograde ureterocelogram in management of complex ureterocele.

INTRODUCTION: Symptomatic pediatric ureterocele has diverse manifestations, making evidence-based management impractical. Thus, detailed visualization of ureterocele anatomy prior to first surgical incision is invaluable. Retrograde ureterocelogram (RUC) is a simple, underutilized radiologic technique that can be performed during cystoscopy. This study sought to determine whether RUC changes surgical management by more accurately depicting the complex ureteral and ureterocele anatomy, compared with renal ultrasound (US) and voiding cystourethrography (VCUG). METHODS: Patients who underwent surgical management of ureterocele from 2003 to 2015 were identified; those who received concomitant fluoroscopic RUC were selected for the case series. Data collected included: demographics, pre-operative evaluation, surgical interventions, and outcomes. The RUC images were individually examined, and the anatomic impression compared with previous renal US and VCUG. Novel RUC findings not previously appreciated by the pre-operative evaluation were noted. The RUC was performed by cystoscopically inserting a needle into the ureterocele and injecting contrast retrograde. If indicated, simultaneous PIC (Positioning the Instillation of Contrast) cystography was performed. RESULTS: Of the 43 patients that underwent surgery for suspected ureterocele, 28 underwent cystoscopy + RUC (10 M: 18 F) at a median age of 4.6 months and median follow-up of 37.0 months. All patients had prior US, 25 had prior VCUG, and 20 had prior radionuclide studies. Ureteroceles were either duplex system (n = 21) or single system (n = 7); 17 were ectopic into the bladder neck or urethra; seven were intravesical; and four were pseudoureteroceles. Fourteen patients underwent concomitant transurethral incision of the ureterocele (TUIU); two were deferred for surgery; and 11 received concomitant definitive surgery (e.g., nephrectomy). The RUC illuminated novel aspects of the anatomy in 20 of the 28 patients. No adverse events occurred. Notably, in nine of the 28 children, significant observations from RUC prompted change to the pre-operative surgical plan. DISCUSSION: Retrograde ureterocelogram clearly revealed ureterocele ectopy, pseudoureterocele, ureterocele disproportion, and unsuspected duplex systems, making it a useful adjunct to standard US and VCUG studies. Retrograde ureterocelogram can also be used to fluoroscopically verify decompression of the ureterocele post incision, document severity of ureteral dilation, and teach residents about the great damage generated by ureterocele variations. Limitations of RUC included increasing radiation dose and overall cost. The study design was limited by its small size, retrospective approach, selection bias, and availability of RUC images. CONCLUSIONS: While not indicated in routine ureterocele management, intraoperative RUC further defined ureterocele anatomy in nearly all cases and yielded changes to the original surgical plan frequently enough to merit greater use in complex patients.

Pediatric laparo-endoscopic single site partial nephrectomy: feasibility in infants and small children for upper urinary tract duplication anomalies.

OBJECTIVE: To assess the feasibility and outcomes of laparo-endoscopic single site (LESS) partial nephrectomy (PN) in infants and small children for upper urinary tract duplication anomalies. MATERIALS AND METHODS: The medical records of all patients undergoing LESS PN at a single pediatric institution were retrospectively reviewed for patient demographics, perioperative details, and outcomes. A cystoscopy was initially performed to place an externalized catheter into the ureter of the ipsilateral normal renal moiety. An Olympus TriPort, an Olympus Endoeye flexible tip laparoscope, standard 3- or 5-mm instrumentation, and a LigaSure Blunt were utilized. RESULTS: Four children (two boys, two girls) underwent LESS PN. Three patients underwent upper pole PN and one underwent lower pole PN. All procedures were performed for poorly functioning obstructed renal moieties (one ureterocele, one ureteropelvic junction obstruction and vesicoureteral reflux, and two ectopic ureters). Median age was 6.2 months (range 2.5-16.4 months). Median weight was 7.7 kg (range 6.1-12.6 kg). Median operative time was 126 min (range 97-180 min). No patient received inpatient postoperative narcotics. Median follow-up was 9.9 months (range 6.2-19.1 months). No postoperative complications were noted. Postoperative renal ultrasound demonstrated successful resection in all patients. CONCLUSIONS: LESS PN is technically feasible, safe, and effective for upper urinary tract duplication anomalies in infants and small children.

Infant robotic pyeloplasty: comparison with an open cohort.

OBJECTIVE: To present our experience with infant pyeloplasty, comparing outcomes between robotic-assisted laparoscopic pyeloplasty (RALP) and open pyeloplasty (OP). MATERIALS AND METHODS: A retrospective review was performed of all children <1 year of age who underwent unilateral dismembered pyeloplasty at a single pediatric institution since January 2007. Patients with standard laparoscopic pyeloplasty were excluded. Patient demographics, intraoperative details, narcotic usage, and complications were reviewed. RESULTS: A total of 70 infants (51 boys and 19 girls) were identified, with nine RALP and 61 OP performed. Median age was 9.2 months (range, 3.7-11.9 months) for RALP and 4.1 months (range, 1.0-11.6 months) for OP (p = 0.005). Median weight was 8 kg (range, 5.8-10.9 kg) for RALP and 7 kg (range, 4-14 kg) for OP (p = 0.163). Median operative time was 115 min (range, 95-205 min) for RALP and 166 min (range, 79-300 min) for OP (p = 0.028). Median hospital stay was 1 day (range, 1-2 days) for RALP and 3 days (range, 1-7 days) for OP (p < 0.001). Median postoperative narcotic use of morphine equivalent was <0.01 mg/kg/day (range, 0-0.1 mg/kg/day) for RALP and 0.05 mg/kg/day (range, 0-2.2 mg/kg/day) for OP (p < 0.001). Median follow-up was 10 months (range, 7.2-17.8 months) for RALP and 43.6 months (3.4-73.8 months) for OP (p < 0.001). The success rate was 100% for RALP and 98% for OP. CONCLUSIONS: Infant RALP was observed to be feasible and efficacious with shorter operative time, hospital stay, and narcotic utilization than OP.

Testicular germ cell tumors. Current concepts and management strategies.

Testicular germ cell tumors (T-GCTs) are the most common solid tumor in adolescent and young adult men. Due to the success of multidisciplinary management, the prognosis of all stages of T-GCT is quite good. The development of complimentary therapeutic strategies including modern cytotoxic chemotherapy regimens, appropriate utilization of radiotherapy, and timely surgical resection has made T-GCTs the model of a "curative" malignancy. Herein we review the background, epidemiology, and genetics of the disease, as well as an approach to its diagnosis and staging, including rationale for managing T-GCT in its various stages. In summary, while some areas in T-GCT care are debated, the vast majority of patients should be approached in a standardized manner which ensures optimal oncologic outcomes and minimal therapeutic morbidity.