Pediatric Small Renal Masses: Can Tumor Size Predict Histology and the Potential for Nephron-sparing Surgery?

PURPOSE: The majority of children with unilateral renal masses suspicious for malignancy undergo radical nephrectomy, while nephron-sparing surgery is reserved for select cases. We investigated the impact of tumor size on the probability of histology. We hypothesized that pediatric small renal masses are more likely benign or non-Wilms tumor, thus potentially appropriate for nephron-sparing surgery. MATERIALS AND METHODS: The SEER (Surveillance, Epidemiology, and End Results) database was analyzed for patients aged 0-18 years diagnosed with a unilateral renal mass from 2000-2016. Statistical analysis was performed to help determine a tumor size cut point to predict Wilms tumor and assess the predictive value of tumor size on Wilms tumor histology. Additionally, a retrospective review was performed of patients 0-18 years old who underwent surgery for a unilateral renal mass at a single institution from 2005-2019. Statistical analysis was performed to assess the predictive value of tumor size on final histology. RESULTS: From the SEER analysis, 2,016 patients were included. A total of 1,672 tumors (82.9%) were Wilms tumor. Analysis revealed 4 cm to be a suitable cut point to distinguish non-Wilms tumor. Tumors ≥4 cm were more likely Wilms tumor (OR 2.67, P ≤ .001), but this was driven by the statistical significance in children 5-9 years old. From the institutional analysis, 134 patients were included. Ninety-seven tumors (72.3%) were Wilms tumor. Tumors ≥4 cm had higher odds of being Wilms tumor (OR 30.85, P = .001), malignant (OR 6.75, P = .005), and having radical nephrectomy-appropriate histology (OR 46.79, P < .001). CONCLUSIONS: The probability that a pediatric unilateral renal mass is Wilms tumor increases with tumor size. Four centimeters is a logical cut point to start the conversation around defining pediatric small renal masses and may help predict nephron-sparing surgery-appropriate histology.

White paper: Oncofertility in pediatric patients with Wilms tumor.

The survival of childhood Wilms tumor is currently around 90%, with many survivors reaching reproductive age. Chemotherapy and radiotherapy are established risk factors for gonadal damage and are used in both COG and SIOP Wilms tumor treatment protocols. The risk of infertility in Wilms tumor patients is low but increases with intensification of treatment including the use of alkylating agents, whole abdominal radiation or radiotherapy to the pelvis. Both COG and SIOP protocols aim to limit the use of gonadotoxic treatment, but unfortunately this cannot be avoided in all patients. Infertility is considered one of the most important late effects of childhood cancer treatment by patients and their families. Thus, timely discussion of gonadal damage risk and fertility preservation options is important. Additionally, irrespective of the choice for preservation, consultation with a fertility preservation (FP) team is associated with decreased patient and family regret and better quality of life. Current guidelines recommend early discussion of the impact of therapy on potential fertility. Since most patients with Wilms tumors are prepubertal, potential FP methods for this group are still considered experimental. There are no proven methods for FP for prepubertal males (testicular biopsy for cryopreservation is experimental), and there is just a single option for prepubertal females (ovarian tissue cryopreservation), posing both technical and ethical challenges. Identification of genetic markers of susceptibility to gonadotoxic therapy may help to stratify patient risk of gonadal damage and identify patients most likely to benefit from FP methods.

Enhanced recovery after surgery and anesthetic outcomes in pediatric reconstructive urologic surgery.

PURPOSE: Enhanced recovery after surgery (ERAS) is a perioperative management strategy to hasten postoperative recovery. We examined the effects of a pilot implementation of ERAS for pediatric patients on anesthetic outcomes. METHODS: We performed a prospective case-control study utilizing an ERAS protocol in patients aged < 18 years undergoing urologic reconstruction that included a bowel anastomosis. Protocol elements included: multimodal analgesia, opioid minimization, and routine nausea/vomiting prophylaxis. ERAS patients were propensity-matched with historical controls. Outcomes of interest included maximum PACU pain score, time to first opioid, opioid-free days, and need for opioids on day of discharge. RESULTS: A total of 13 ERAS patients and 26 historical controls were included, with median ages 9.9 years (IQR 9.1-11) and 10.4 years (IQR 8.0-12.4), respectively. ERAS increased the percentage of patients who did not receive any intraoperative or postoperative opioids (0% vs 15%, p = 0.046 for both) and reduced maximum PACU pain score (3 vs 0, p < 0.001). The use of postoperative supplemental oxygen was decreased in the ERAS group (85% vs 38%, p = 0.013). CONCLUSIONS: The implementation of an ERAS protocol appears to decrease postoperative pain, opioid usage, and positively impact other anesthetic outcomes in children undergoing urologic reconstructive surgery utilizing a bowel anastomosis.

Extirpative renal surgery volume in training: different roads to the (same?) destination.

PURPOSE: To describe the overall extirpative renal surgery (ERS) training volume reported by PU and PS. METHODS: Case log data from the Accreditation Council for Graduate Medical Education (ACGME) was examined from 2013-2016 for surgery residents (Sres), urology residents (Ures), pediatric surgery fellows (PSfel) and pediatric urology fellows (PUfel). Case log information for all levels of participation over all case categories that could potentially offer ERS volume were recorded. Volume was estimated using the mean number of included cases during residency and fellowship and the sum was used to estimate total training volume. Volume between groups was compared using the student's t test. RESULTS: Case logs were included for 4447 residents (4259 Sres, 840 Ures) and fellows (188 PSfel, 71 PUfel). Mean PU volume was 113.1, which was higher than the mean PS volume of 10.3 (p < 0.001). For PU, more ERS were performed during residency than fellowship (p < 0.001). For PS the opposite was true (p < 0.001). When examining fellow training only, PUfel performed more ERS than PSfel (11.7 vs. 7.0 p < 0.001). CONCLUSION: While previous publications note similar short-term outcomes for ERS for malignancy for PU and PS, ERS case volume during training is significantly different. Review of recent ACGME data indicate that PU have more overall experience with ERS, with most gained during residency. Additionally, PUfel performed significantly more ERS than PSfel. Further study into how these training differences affect long-term outcomes is necessary.

The impact of age at orchiopexy on testicular cancer outcomes.

PURPOSE: To estimate how many boys with UDT must undergo orchiopexy to prevent one case of TC, one death from TC and one exposure to TC treatment beyond radical orchiectomy as compared to being treated at an older age. METHODS: This retrospective study utilized data from a 2007 Swedish study of males who underwent orchiopexy for UDT (Pettersson et al.). TC incidence for boys undergoing orchiopexy for UDT was assessed based on the age at orchiopexy (0-6 years, 7-9 years, 10-12 years, 13-15 years). The incidence of TC in each age cohort was calculated and used to determine the number needed to treat (NNT) for each age group using assumptions based on published TC outcomes. RESULTS: For an index patient ≤ 6 years, 372 boys need to undergo orchiopexy to prevent a single case of TC, 1488 boys to prevent exposure to TC therapy beyond radical orchiectomy, and 5315 boys to prevent a single TC-related death compared to treatment at an older age. CONCLUSION: While there is evidence supporting benefits of early orchiopexy, the NNT to affect TC outcomes is very high. Even those with delayed orchiopexies have low risk for TC poor outcomes. This information can be used when counseling patients and families faced with UDT about the risks related to TC, especially with comorbidities.

Surgical management of pediatric renal masses: surgeon subspecialty practice patterns.

INTRODUCTION: Management of pediatric renal masses has lagged behind adult paradigms adopting minimally invasive surgery (MIS) and nephron-sparing surgery (NSS). This study investigated national practice patterns between pediatric urologists (PU) and pediatric surgeons (PS) in pediatric renal malignancy. MATERIALS AND METHODS: The Pediatric National Surgical Quality Improvement Program database was queried for CPT codes for radical/partial nephrectomy from 2012-2017 performed for renal malignancy. Patients were grouped by specialty and operative approach. RESULTS: PU managed 175 (17%) patients while PS managed 811 (77%). PU were more likely to use MIS (14% versus 5%, p < 0.001) and NSS (33% versus 13%, p < 0.001) compared to PS. PS more commonly performed lymph node (LN) sampling/tumor thrombectomy, especially in MIS cases (67% versus 35%, p = 0.008). PS operated on younger patients with higher ASA class compared to PU, but had higher transfusion rates and longer length of stay. Central venous access surgery was more commonly performed on patients operated on by PS, while PU performed more cystoscopy/retrograde pyelography. Patients who underwent NSS compared to radical nephrectomy were less likely to undergo LN sampling, while LN sampling did not differ between open and MIS groups. CONCLUSIONS: PU were likely to perform MIS and NSS than PS for pediatric renal masses in this national database. This likely results from inherent training differences between PS and PU and reflects emerging data on safety and efficacy of these advanced surgical techniques. Further investigation into the impact on oncologic and clinical outcomes by surgical specialty and operative approach is necessary.

Pediatric pheochromocytoma: current status of diagnostic imaging and treatment procedures.

PURPOSE OF REVIEW: To provide an overview of relevant data available and updated recommendations for management of pediatric patients with pheochromocytoma (PCC). RECENT FINDINGS: Much of the available data surrounding pediatric PCC is in the form of case reports and case series. With the accumulation of data over time, pediatric PCC does in fact differ significantly from not only what is known in the adult population, but also from classic teaching. Pediatric patients are much more likely to have a hereditary predisposition as well as aggressive and malignant disease. Much of the recent literature focuses on defining these genetic syndromes in order to provide recommendations for screening and genetic counseling. Other recent advances center around developing treatments for metastatic disease. Timely diagnosis with plasma metanephrines and cross-sectional imaging, and appropriate preoperative medical optimization followed by surgical resection remain the center of treatment. SUMMARY: Although rare and adult principles are applied to pediatric PCC, genetic testing plays a pivotal role in management of children, adolescents and young adults with PCC.

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.

Current Treatment of Pediatric Bladder and Prostate Rhabdomyosarcoma.

PURPOSE OF REVIEW: Rhabdomyosarcoma (RMS) is the most common sarcoma diagnosed in the first 20 years of life; bladder/prostate (BP) RMS accounts for 5% of all cases. Through efforts from multiple cooperative study groups, survival has improved significantly. This article aims to review the complex RMS classification system and treatment of BP RMS, with a focus on developing aspects of treatment. RECENT FINDINGS: Recent advancements in technology are responsible for most of the progress in RMS treatment. PET-CT scanning has been shown to be superior to conventional metastatic workup. The use of proton beam therapy and brachytherapy to reduce the side effects of radiation is also showing promise. All cooperative oncology groups agree on surgical biopsy for diagnosis and staging of BP RMS. Patients are then grouped and risk classified before receiving chemotherapy. Regardless of local control strategy, oncologic outcomes appear to be similar for BP RMS. Alternative treatment strategies, which remain unproven, include brachytherapy and proton therapy.

Neuroblastoma in a Newborn Female.

Neuroblastoma is the most common solid tumor in neonates. Although often aggressive in older children, carrying high mortality rates despite multimodal therapies, neuroblastoma appears to behave differently in the neonatal population. When diagnosis is clear, the disease can often be managed with close observation alone. This is a case of neuroblastoma in a 4-day-old female managed with surgical resection. This case highlights the potential challenges of diagnosis of retroperitoneal masses on prenatal ultrasound and in newborns and the importance of utilizing available resources when making difficult decisions in management.

Unusual Renal Mass in a Pediatric Patient.

Renal cell carcinoma (RCC) is rare in the pediatric population, comprising about 5% of renal neoplasms in children.1 Out of all childhood cases of RCC, translocation RCCs (tRCC) is the most common.2 It is well described in the literature that exposure to alkylating agents such as cyclophosphamide and/or topoisomerase II inhibitors such as doxorubicin and etoposide, is a risk factor for the development of Xp11 (or TFE3) tRCC.3 Herein is a case of tRCC development in a patient with history of exposure to topoisomerase II inhibitors and alkylating agents to treat a common childhood malignancy.

Bilateral Wilms Tumor in CLOVES Syndrome.

Wilms tumor is the most common pediatric renal mass and occurs in up to 10% of predisposition syndromes. One such syndrome is CLOVES syndrome, an extremely rare disorder within the umbrella of PIK3CA-related overgrowth spectrum disorders. This case presents the management of a bilateral Wilms tumor in a patient with CLOVES syndrome and highlights the many intricacies in caring for complex oncology patients. Particularly highlighted in this case is the delicate line in balancing the risks of treatment-related morbidity against the risks of recurrence in predisposed patients, while still abiding by established treatment guidelines.

Wilms Tumor.

Wilms tumor (WT), or nephroblastoma, is the most common primary malignant renal tumor of childhood. It is an embryonal tumor that develops from remnants of immature kidney. There are approximately 500 new WT cases diagnosed in the United States every year. Advances in multimodal therapy including surgery, chemotherapy, and radiation therapy given according to risk stratification have allowed most patients to achieve survival rates in excess of 90%.

"Exogenous" 5 Alpha Reductase Deficiency: A Case Report.

Testosterone and dihydrotestosterone are significant drivers of male external genital development, and therefore teratogens that alter these hormone profiles have been hypothesized to cause aberrations in development. Here, we present the first case report of genitalia anomalies after prenatal exposure to spironolactone and dutasteride through 8-weeks of gestation. The patient was born with abnormal male external genitalia which was surgically managed. Long-term outcomes such as gender identity, sexual function, hormonal maturation through puberty, and fertility remain unknown. These numerous considerations necessitate multi-disciplinary management with close follow-up to address sexual, psychological, and anatomic concerns.

Gonadal tumors in a contemporary cohort of patients with differences in sex development undergoing surgery - A multi-site study from the Pediatric Urologic Oncology Working Group of the societies for pediatric urology.

BACKGROUND: Disturbances in gonadal development lead to increased risk of gonadal malignancy in some but not all patients with differences in sex development (DSD). However, the natural history of these tumors is poorly described, and the literature remains sparse. OBJECTIVE: The objective of this study was to describe the incidence of germ cell neoplasia in situ (GCNIS) and germ cell tumor (GCT) in a contemporary cohort of patients with DSD undergoing surgery and to provide long-term oncologic outcomes for these patients. STUDY DESIGN: Patients with DSD who have undergone gonadectomy or gonadal biopsy were identified at four institutions. Clinical characteristics, pathology, and treatment details were obtained retrospectively. Patients were stratified into risk categories based on DSD diagnosis. Oncologic treatment and outcomes were recorded. Descriptive statistics are reported using parametric methods. RESULTS: 83 patients were identified. Distribution of diagnoses is summarized in the summary table. 14 (16.9%) patients underwent gonadal biopsy, and 71 (85.5%) patients underwent gonadectomy (50/71 gonadectomies were bilateral). 8/83 (9.6%) patients had GCNIS or GCT (7 GCNIS, 1 GCT). Median age at surgery was 2.95 years (y) (interquartile range [IQR] 0.6-12.2) and 14y (IQR 0.85-16.9) in patients without and with GCNIS/GCT, respectively. All 8 patients with GCNIS/GCT had high or intermediate risk DSD diagnoses (4 mixed gonadal dysgenesis, 3 Turner with Y, 1 partial gonadal dysgenesis). Of the patients with high-risk diagnoses, 8/54 (15%) had GCNIS/GCT. No patient received adjuvant therapy, no patient had a recurrence, and all patients were living with mean follow up 6.4y. DISCUSSION: The risk of gonadal malignancy is heterogeneous in the DSD population and can vary based on DSD diagnosis as well as maturation, testicularization, and location of the gonads. The most recent consensus recommendations on gonadal management emphasize risk stratification and consideration of gonadal surveillance based on gender of rearing, but supporting literature remains sparse. In this contemporary cohort of DSD patients who underwent gonadal surgery, most patients did not have evidence of adverse pathology, all patients with malignant or premalignant pathology had a high/intermediate risk DSD diagnosis, and all patients with GCNIS/GCT were treated with surgery alone without recurrence. CONCLUSIONS: The distribution of patients with premalignant and malignant gonadal pathology and DSD in this cohort aligns with prior literature, and oncologic outcomes were excellent. These data add valuable information to the current literature and highlight the necessity to develop appropriate screening regimens for retained gonads.