Development of an enhanced recovery after surgery program for pediatric solid tumors.

Introduction: Enhanced recovery after surgery (ERAS) is an evidence-based, multi-modal approach to decrease surgical stress, expedite recovery, and improve postoperative outcomes. ERAS is increasingly being utilized in pediatric surgery. Its applicability to pediatric patients undergoing abdominal tumor resections remains unknown. Methods and Analysis: A group of key stakeholders adopted ERAS principles and developed a protocol suitable for the variable complexity of pediatric abdominal solid tumor resections. A multi-center, prospective, propensity-matched case control study was then developed to evaluate the feasibility of the protocol. A pilot-phase was utilized prior to enrollment of all patients older than one month of age undergoing any abdominal, retroperitoneal, or pelvic tumor resections. The primary outcome was 90-day complications per patient. Additional secondary outcomes included: ERAS protocol adherence, length of stay, time to administration of adjuvant chemotherapy, readmissions, reoperations, emergency room visits, pain scores, opioid usage, and differences in Quality of Recovery 9 scores. Ethics and Dissemination: Institutional review board approval was obtained at all participating centers. Informed consent was obtained from each participating patient. The results of this study will be presented at pertinent society meetings and published in peer-reviewed journals. We expect the results will inform peri-operative care for pediatric surgical oncology patients and provide guidance on initiation of ERAS programs. We anticipate this study will take four years to meet accrual targets and complete follow-up. Trial Registration Number: NCT04344899.

Current surgical approaches to pediatric renal tumors.

Pediatric renal tumors are among the most common pediatric solid malignancies. Surgical resection is a key component in the multidisciplinary therapy for children with kidney tumors. Therefore, it is imperative that surgeons caring for children with renal tumors fully understand the current standards of care in order to provide appropriate surgical expertise within this multimodal framework. Fortunately, the last 60 years of international, multidisciplinary pediatric cancer cooperative group studies have enabled high rates of cure for these patients. This review will highlight the international surgical approaches to pediatric patients with kidney cancer to help surgeons understand the key differences and similarities between the European (International Society of Pediatric Oncology) and North American (Children's Oncology Group) recommendations.

Bilateral Wilms tumor with anaplasia: A report from the Children's Oncology Group Study AREN0534.

INTRODUCTION: The purpose of this study is to examine the outcomes in children with anaplastic bilateral Wilms tumor (BWT) from study AREN0534 in order to define potential prognostic factors and areas to target in future clinical trials. METHODS: Demographic and clinical data from AREN0534 study patients with anaplasia (focal anaplasia [FA], or diffuse anaplasia [DA]) were compared. Event-free survival (EFS) and overall survival (OS) were reported using Kaplan-Meier estimation with 95% confidence bands, and differences in outcomes between FA and DA compared using log-rank tests. The impact of margin status was analyzed. RESULTS: Twenty-seven children who enrolled on AREN0534 had evidence of anaplasia (17 DA, 10 FA) in at least one kidney and were included in this analysis. Twenty-six (96%) had BWT. Nineteen percent had anaplastic histology in both kidneys (four of 17 DA, and one of 10 FA). Forty-six percent with BWT had bilateral nephron-sparing surgery (NSS); one child who went off protocol therapy, eventually required bilateral completion nephrectomies. Median follow-up for EFS and OS was 8.6 and 8.7 years from enrollment. Four- and 8-year EFS was 53% [95% confidence interval (CI): 34%-83%] for DA; 4-year EFS was 80% [95% CI: 59%-100%], and 8-year EFS 70% [95% CI: 47%-100%] for FA. Three out of 10 children with FA and eight out of 17 children with DA had events. EFS did not differ statistically by margin status (p = .79; HR = 0.88). Among the six children who died (five DA, one FA), all experienced prior relapse or progression within 18 months. CONCLUSION: Events in children with DA/FA in the setting of BWT occurred early. Caution should be taken about interpreting the impact of margin status outcomes in the context of contemporary multimodal therapy. Future targeted investigations in children with BWT and DA/FA are needed.

Race and Ethnic Group Enrollment and Outcomes for Wilms Tumor: Analysis of the Current Era Children's Oncology Group Study, AREN03B2.

BACKGROUND: To review race and ethnic group enrollment and outcomes for Wilms tumor (WT) across all 4 risk-assigned therapeutic trials from the current era Children's Oncology Group Renal Tumor Biology and Risk Stratification Protocol, AREN03B2. STUDY DESIGN: For patients with WT enrolled in AREN03B2 (2006 to 2019), disease and biologic features, therapeutic study-specific enrollment, and event-free (EFS) and overall (OS) 4-year survival were compared between institutionally reported race and ethnic groups. RESULTS: Among 5,146 patients with WT, no statistically significant differences were detected between race and ethnic groups regarding subsequent risk-assigned therapeutic study enrollment, disease stage, histology, biologic factors, or overall EFS or OS, except the following variables: Black children were older and had larger tumors at enrollment, whereas Hispanic children had lower rates of diffuse anaplasia WT and loss of heterozygosity at 1p. The only significant difference in EFS or OS between race and ethnic groups was observed among the few children treated for diffuse anaplasia WT with regimen UH-1 and -2 on high-risk protocol, AREN0321. On this therapeutic arm only, Black children showed worse EFS (hazard ratio = 3.18) and OS (hazard ratio = 3.42). However, this finding was not replicated for patients treated with regimen UH-1 and -2 under AREN03B2 but not on AREN0321. CONCLUSIONS: Race and ethnic group enrollment appeared constant across AREN03B2 risk-assigned therapeutic trials. EFS and OS on these therapeutic trials when analyzed together were comparable regarding race and ethnicity. Black children may have experienced worse stage-specific survival when treated with regimen UH-1 and -2 on AREN0321, but this survival gap was not confirmed when analyzing additional high-risk AREN03B2 patients.

Peripubertal Presentation of Metastatic Testicular Mixed, Nonseminomatous Germ Cell Tumor.

Testicular tumors are relatively rare in children and those in prepubertal children tend to present with different histological types and behaviors than their postpubertal counterparts. The majority of these pre- and peripubertal testicular tumors tend to be benign and those that are malignant, tend to present at low stages, not generally requiring systemic treatment. Here we present a rare case of a peri-pubertal, mixed nonseminomatous germ cell tumor of the testes which was found to be widely metastatic at presentation, classifying as poor risk disease.

Children's Oncology Group's 2023 blueprint for research: Surgery.

Surgery plays a crucial role in the treatment of children with solid malignancies. A well-conducted operation is often essential for cure. Collaboration with the primary care team is important for determining if and when surgery should be performed, and if performed, an operation must be done in accordance with well-established standards. The long-term consequences of surgery also need to be considered. Indications and objectives for a procedure vary. Providing education and developing and analyzing new research protocols that include aims relevant to surgery are key objectives of the Surgery Discipline of the Children's Oncology Group. The critical evaluation of emerging technologies to ensure safe, effective procedures is another key objective. Through research, education, and advancing technologies, the role of the pediatric surgeon in the multidisciplinary care of children with solid malignancies will continue to evolve.

Use of Peripheral Intravenous Access in Patients Undergoing Chemotherapy for Testicular Cancer.

PURPOSE: Systemic chemotherapy, depending on the regimen, can be administered through peripheral intravenous (pIV) access or through central venous access devices (CVADs). There is no current best practice regarding optimal access for chemotherapy for patients with testicular cancer (TC). We retrospectively evaluated patients undergoing systemic chemotherapy for TC and compared baseline characteristics and complications of patients using pIV versus CVADs. METHODS: We included patients with TC who underwent first-line systemic chemotherapy at the University of Colorado Hospitals from 2005 to 2020. Data were collected on demographics, cancer characteristics, type, duration of chemotherapy, pIV or CVAD use, and associated complication rates. We then performed univariate and multivariate regression analyses to compare complication rates and risk factors for each group. RESULTS: One hundred fifty-four patients met inclusion criteria. Ninety-two (60%) patients used CVADs, and 62 patients (40%) used pIV for their initial treatment. Only six (9.7%) of 62 patients transitioned from pIV to CVADs during therapy. Similarly, 10 of 92 (10.9%) patients with initial CVAD needed to transition to a different type of CVAD or to pIV (P = .81). There were a greater number of venous access-related complications (48 of 92 patients, 52.2%) and overall thrombotic events (33 of 92 patients, 35.9%) for the CVAD group (P > .001) when compared with the pIV group. We observed an association between the following factors and venous access-related complications during chemotherapy: higher stage TC, increased total chemotherapy cycles, and delayed therapy. CONCLUSION: Peripheral IV use for first-line nonvesicant chemotherapy in patients with TC appears to be well tolerated with high rates of therapy completion and lower rates of complications when compared with CVADs. These data support our preferred treatment approach and provide evidence that pIV access is a safe and effective way to deliver chemotherapy for patients with TC.

Critical elements of pediatric testicular germ cell tumors surgery.

Children, adolescents and young adults with testicular germ cell tumors require appropriate surgical care to insure excellent outcomes. This article presents the most critical elements, and their basis in evidence, for surgery in this population. Specifically, the importance of inguinal radical orchiectomy for malignant tumors, partial orchiectomy for prepubertal tumors and normal serum tumor markers, and the appropriate use of post-chemotherapy retroperitoneal lymph node dissection in those with residual retroperitoneal masses.

Critical elements of radical nephroureterectomy for pediatric unilateral renal tumor.

Children with renal masses require surgical management to provide accurate surgical staging and skilled resection of the tumor. This document includes evidence-based recommendations for pediatric surgeons regarding the resection, staging, and proper nodal basin evaluation.

Children's Oncology Group's 2023 blueprint for research: Renal tumors.

Every year, approximately 600 infants, children, and adolescents are diagnosed with renal cancer in the United States. In addition to Wilms tumor (WT), which accounts for about 80% of all pediatric renal cancers, clear cell sarcoma of the kidney, renal cell carcinoma, malignant rhabdoid tumor, as well as more rare cancers (other sarcomas, rare carcinomas, lymphoma) and benign tumors can originate within the kidney. WT itself can be divided into favorable histology (FHWT), with a 5-year overall survival (OS) exceeding 90%, and anaplastic histology, with 4-year OS of 73.7%. Outcomes of the other pediatric renal cancers include clear cell sarcoma (5-year OS: 90%), malignant rhabdoid tumor (5-year OS: 10% for stages 3 and 4), and renal cell carcinoma (4-year OS: 84.8%). Recent clinical trials have identified novel biological prognostic markers for FHWT, and a series of Children's Oncology Group (COG) trials have demonstrated improving outcomes with therapy modification, and opportunities for further care refinement.

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%.

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.

Nephron sparing surgery and surgical management of intravascular extension of Wilms tumor.

Although general treatment approaches for Wilms tumor differ between Children's Oncology Group and Société Internationale d'Oncologie Pédiatrique-Renal Tumors Study Group protocols, complex tumors that may be candidates for nephron sparing surgery (NSS) and those with intravascular tumor extension represent a management challenge. In both of these scenarios, anatomic considerations are important in guiding management, making these areas of significant similarities in management between the international groups. This paper aims to explore the current approaches to NSS and intravascular tumor extension by both international groups, with attention to the evidence supporting these approaches and current knowledge gaps.

Vaginal Rhabdoid Tumor Presenting as Prenatal Lower Urinary Tract Obstruction and Vaginal Mass.

Extracranial malignant rhabdoid tumors (MRT) are very rare and aggressive tumors. They are typically associated with an extremely poor prognosis, particularly when seen in the infant and neonatal population. Here we present the case of a newborn female born with a large vaginal mass and evidence of prenatal lower urinary tract obstruction that was determined to be a MRT of vaginal origin. In this report, we will also discuss an overview of extracranial MRT tumor biology and treatment considerations.

Extended Lymph Node Sampling During Surgery for Pediatric Renal Tumors Concerning for Malignancy Does Not Increase Postoperative Complication Rates.

PURPOSE: Although Children's Oncology Group renal tumor protocols mandate lymph node sampling during extirpative surgery for pediatric renal tumors, lymph node sampling is often omitted or low yield. Concerns over morbidity associated with extended lymph node sampling have led to hesitancy in adopting a formal lymph node sampling template. We hypothesized that complications in children undergoing lymph node sampling for renal tumors would be rare, and not associated with the number of lymph nodes sampled. MATERIALS AND METHODS: A single-institution, retrospective review of patients aged 0-18 years undergoing extirpative renal surgery with lymph node sampling for a suspected malignancy between 2005 and 2019 was performed. Patients with 0 or an unknown number of lymph nodes sampled or <150 days of follow-up were excluded. A "clinically significant" complication was defined as any Clavien complication ≥III, small-bowel obstruction, chylous ascites, organ injury, or wound infection. The number of lymph nodes sampled and its influence on the odds of experiencing a clinically significant complication was examined. RESULTS: A total of 144 patients met inclusion criteria. Median patient age was 38 months. Twenty-one patients (15%) had a clinically significant complication, the most common of which was ileus/small-bowel obstruction (n=16). In a multivariable analysis, increased lymph node yield was not found to influence the odds of experiencing a clinically significant complication (P = .6). CONCLUSIONS: In this cohort, there was no statistically significant difference in clinically significant complications in patients who underwent more extensive lymph node sampling during surgery for a suspected malignant pediatric renal tumor. Future studies on protocol adherence, staging accuracy, and survival trends using a lymph node sampling template in these patients should be performed.

Multifocal Paraganglioma in Teenager Presenting With Hypertension.

Pediatric hypertension represents a rare though increasingly common medical problem. When encountered, a workup to determine the etiology should be conducted. In this report, we detail an unusual case in which a teenager presenting with hypertension was found to have multifocal primary paragangliomas. We illustrate important considerations in management which include appropriate preoperative labs and imaging, collaboration with endocrinology for preoperative alpha-blockade, surgical management with close perioperative hemodynamic control, and genetic evaluation for all patients with paragangliomas.