Hepatic Metastasectomy in Pediatric Patients: An Observational Study.

BACKGROUND: The role of hepatectomy for metastatic disease in children is controversial. Rationales include potential cure, obtaining a diagnosis, and guiding chemotherapy decisions. This study examines the safety and utility of hepatic metastasectomy for children at a single institution. METHODS: After IRB approval (#22-1258), medical records were reviewed from 1995 to 2022 for children undergoing hepatic metastasectomy. En-bloc hepatectomies during primary tumor resection were excluded. RESULTS: Hepatic metastasectomy was performed in 16 patients for a variety of histologies. Median patient age was 12.2 years [IQR 6.9-22.6], and 13/16 patients were female (81 %). Number of hepatic metastases ranged from 1 to 23 and involved between 1 and 8 Couinaud segments. Anatomic resections included 4 hemihepatectomies and 1 sectionectomy. All other resections were nonanatomic. 3/6 resections for germ cell tumor (GCT) revealed only mature teratoma, driving adjuvant therapy decisions. When indicated, median time to adjuvant chemotherapy was 19 days [IQR 11-22]. No patients had Clavien-Dindo Class III or higher perioperative morbidity. Three patients (1 GCT, 1 adrenocortical carcinoma (ACC), and 1 gastric neuroendocrine tumor (GNET) experienced hepatic relapse. The patients with relapsed GCT and GNET are alive with disease at 17 and 135 months, respectively. The patient with ACC died of disease progression and liver failure. One patient with Wilms tumor experienced extrahepatic, retroperitoneal recurrence and died. With a median follow-up of 38 months, 10-year disease-specific and disease-free survival were 77 % and 61 %, respectively. CONCLUSIONS: Hepatic metastasectomy can be accomplished safely in children, may guide adjuvant therapy decisions, and is associated with long-term survival in selected patients. LEVEL OF EVIDENCE: Level IV. TYPE OF STUDY: Treatment Study, Case series with no comparison group.

Aggressive Pursuit of No Evidence of Disease Status in Hepatoblastoma Improves Survival: An Observational Study.

BACKGROUND: The utility of repeated surgical interventions in hepatoblastoma to achieve no evidence of disease (NED) is not well-defined. We examined the effect of aggressive pursuit of NED status on event-free (EFS) and overall survival (OS) in hepatoblastoma with subgroup analysis of high-risk patients. METHODS: Hospital records were queried for patients with hepatoblastoma from 2005 to 2021. Primary outcomes were OS and EFS stratified by risk and NED status. Group comparisons were performed using univariate analysis and simple logistic regression. Survival differences were compared with log-rank tests. RESULTS: Fifty consecutive patients with hepatoblastoma were treated. Forty-one (82%) were rendered NED. NED was inversely correlated with 5-year mortality (OR 0.006; CI 0.001-0.056; P < .01). Ten-year OS (P < .01) and EFS (P < .01) were improved by achieving NED. Ten-year OS was similar between 24 high-risk and 26 not high-risk patients when NED was attained (P = .83). Fourteen high-risk patients underwent a median of 2.5 pulmonary metastasectomies, 7 for unilateral disease, and 7 for bilateral, with a median of 4.5 nodules resected. Five high-risk patients relapsed, and three were salvaged. CONCLUSIONS: NED status is necessary for survival in hepatoblastoma. Repeated pulmonary metastasectomy and/or complex local control strategies to obtain NED can achieve long-term survival in high-risk patients. LEVEL OF EVIDENCE: Level III - Treatment Study - Retrospective Comparative Study.

Impact of insertion site on complications in central venous access devices.

PURPOSE: There is still debate over the safest route for the placement of long-term central venous access devices. The aim of this study was to review a large, single-institution experience to determine the impact of access location on peri-operative complications. METHODS: The records of patients undergoing subcutaneous port (SQP) and tunneled catheter insertion over a seven-year period were reviewed. Vein cannulated (subclavian (SCV) versus internal jugular (IJ) vein), and 30-day complications were assessed. Surgical complications included pneumothorax, hemothorax, infections, arrhythmia or malpositioning requiring intervention. RESULTS: A total of 1,309 patients were included (618 SQP, 691 tunneled catheters). The location for insertion was SCV (909, 69.4%) and IJ (400, 30.6%). There were 69 complications (5.2%) (41, 4.5% SCV, 28, 7.0% IJV) including: malpositioning/malfunctioning (SCV 13, 1.4% and IJV 14, 3.0%), pneumothorax (SCV 4, 0.4% and IJV 1, 0.3%), hemothorax (SCV 0 and IJV 1, 0.3%), arrhythmia (SCV 1, 0.1%, and IJV 0), and infection within 30 days of placement (SCV 20, 2.2% and IJ 11, 2.8%). The complication rates were not significantly different based on site (p = 0.080). CONCLUSION: There was no significant difference in complication rates when using the subclavian versus the internal jugular vein as the site for long-term central venous access. LEVEL OF EVIDENCE: III, retrospective comparative study.

Histologic type predicts disparate outcomes in pediatric hepatocellular neoplasms: A Pediatric Surgical Oncology Research Collaborative study.

BACKGROUND: Hepatocellular carcinoma (HCC) is a rare cancer in children, with various histologic subtypes and a paucity of data to guide clinical management and predict prognosis. METHODS: A multi-institutional review of children with hepatocellular neoplasms was performed, including demographic, staging, treatment, and outcomes data. Patients were categorized as having conventional HCC (cHCC) with or without underlying liver disease, fibrolamellar carcinoma (FLC), and hepatoblastoma with HCC features (HB-HCC). Univariate and multivariate analyses identified predictors of mortality and relapse. RESULTS: In total, 262 children were identified; and an institutional histologic review revealed 110 cHCCs (42%; 69 normal background liver, 34 inflammatory/cirrhotic, 7 unknown), 119 FLCs (45%), and 33 HB-HCCs (12%). The authors observed notable differences in presentation and behavior among tumor subtypes, including increased lymph node involvement in FLC and higher stage in cHCC. Factors associated with mortality included cHCC (hazard ratio [HR], 1.63; P = .038), elevated α-fetoprotein (HR, 3.1; P = .014), multifocality (HR, 2.4; P < .001), and PRETEXT (pretreatment extent of disease) stage IV (HR, 5.76; P < .001). Multivariate analysis identified increased mortality in cHCC versus FLC (HR, 2.2; P = .004) and in unresectable tumors (HR, 3.4; P < .001). Disease-free status at any point predicted survival. CONCLUSIONS: This multi-institutional, detailed data set allowed a comprehensive analysis of outcomes for children with these rare hepatocellular neoplasms. The current data demonstrated that pediatric HCC subtypes are not equivalent entities because FLC and cHCC have distinct anatomic patterns and outcomes in concert with their known molecular differences. This data set will be further used to elucidate the impact of histology on specific treatment responses, with the goal of designing risk-stratified algorithms for children with HCC. LAY SUMMARY: This is the largest reported granular data set on children with hepatocellular carcinoma. The study evaluates different subtypes of hepatocellular carcinoma and identifies key differences between subtypes. This information is pivotal in improving understanding of these rare cancers and may be used to improve clinical management and subsequent outcome in children with these rare malignancies.

Improving pathways to eliminate underrepresentation in the pediatric surgery workforce: A call to action.

Despite progress, diversity and minority representation within the pediatric surgery workforce still does not match the expansive backgrounds of the patients we treat. The problem stems from underrepresentation of minority populations at every step along the pediatric surgery training pathway. Strategies aimed at improving diversity and representation in medical school, general surgery residencies, and ultimately pediatric surgery fellowship are necessary to assemble a more diverse pool of pediatric surgeons. The aim of this paper is to review the current demographic make-up of medical and surgical specialties, highlight the value of diversity, and provide evidence-based strategies for increasing minority representation throughout the pediatric surgery pathway. Future patients will be better served with a more representative pediatric surgery workforce.

Impact of Neoadjuvant Chemotherapy on Image-Defined Risk Factors in High-Risk Neuroblastoma.

PURPOSE: Image-defined risk factors (IDRFs) are associated with surgical risks in neuroblastoma. We sought to evaluate the impact of neoadjuvant therapy on IDRFs and associated ability to achieve gross total resection (GTR) of locoregional disease in patients with high-risk neuroblastoma. METHODS: We retrospectively reviewed charts of patients treated on four consecutive high-risk neuroblastoma protocols over a 20-year period at a single institution. The number of IDRFs at diagnosis and just prior to surgery, and the percent decrease of tumor volume from just prior to surgery to the end of induction were determined. RESULTS: Eighty-eight patients were included. There were 438 IDRFs (average 5.0 ± 3.1 per patient) at diagnosis and 198 (average 2.3 ± 1.9 per patient) after neoadjuvant chemotherapy (p < 0.01). A reduction in IDRFs was seen in 81.8% of patients with average decrease of 2.9 ± 2.5 per patient. The average percent reduction in tumor volume was 89.8 ± 18.9% and correlated with the number of IDRFs present after chemotherapy (p < 0.01). Three or fewer IDRFs prior to surgery was associated with the highest odds ratio for > 90% GTR at 9.33 [95% confidence interval 3.14-31.5]. CONCLUSION: Neoadjuvant chemotherapy reduced the number of IDRFs in the majority of patients with high-risk neuroblastoma. The number of IDRFs present after neoadjuvant therapy correlated with the extent of resection.

Implications of Tumor Characteristics and Treatment Modality on Local Recurrence and Functional Outcomes in Children With Chest Wall Sarcoma: A Pediatric Surgical Oncology Research Collaborative Study.

OBJECTIVE: To determine the impact of tumor characteristics and treatment approach on (1) local recurrence, (2) scoliosis development, and (3) patient-reported quality of life in children with sarcoma of the chest wall. SUMMARY OF BACKGROUND DATA: Children with chest wall sarcoma require multimodal therapy including chemotherapy, surgery, and/or radiation. Despite aggressive therapy which places them at risk for functional impairment and scoliosis, these patients are also at significant risk for local recurrence. METHODS: A multi-institutional review of 175 children (median age 13 years) with chest wall sarcoma treated at seventeen Pediatric Surgical Oncology Research Collaborative institutions between 2008 and 2017 was performed. Patient-reported quality of life was assessed prospectively using PROMIS surveys. RESULTS: The most common diagnoses were Ewing sarcoma (67%) and osteosarcoma (9%). Surgical resection was performed in 85% and radiation in 55%. A median of 2 ribs were resected (interquartile range = 1-3), and number of ribs resected did not correlate with margin status ( P = 0.36). Local recurrence occurred in 23% and margin status was the only predictive factor(HR 2.24, P = 0.039). With a median follow-up of 5 years, 13% developed scoliosis (median Cobb angle 26) and 5% required corrective spine surgery. Scoliosis was associated with posteriorrib resection (HR 8.43; P= 0.003) and increased number of ribs resected (HR 1.78; P = 0.02). Overall, patient-reported quality of life is not impaired after chest wall tumor resection. CONCLUSIONS: Local recurrence occurs in one-quarter of children with chest wall sarcoma and is independent of tumor type. Scoliosis occurs in 13% of patients, but patient-reported quality of life is excellent.

Does epidural analgesia really enhance recovery in pediatric surgery patients?

PURPOSE: We sought to determine the benefits of epidural anesthesia (EA) in pediatric surgical patients. METHODS: This study is a single-institution retrospective review of EA for pediatric patients undergoing thoracotomy or laparotomy from 2015 to 2020. Patients with recent or chronic opioid use were excluded. Urgent or emergent cases, patients with hemodynamic instability, or those with surgical complications that significantly impacted their post-operative course were also excluded. The primary objectives were comparison of pain scores and systemic opioid use between those patients with EA and those without EA. RESULTS: Epidural anesthesia was used in 151 (81.6%) laparotomies and 58 (77.3%) thoracotomies. EA use was associated with lower mean systemic opioid administration during the early post-operative period for laparotomy (POD#0-0.33 ± 0.3 oral morphine equivalents per kilogram (OME/Kg) with EA vs 0.93 ± 1.53, p < 0.001, POD#1-1.34 ± 1.79 OME/Kg with EA vs 2.61 ± 2.60, p < 0.001) and thoracotomy (POD#0-0.40 ± 0.37 OME/Kg with EA vs 0.68 ± 0.41, p = 0.008, POD#1-0.89 ± 0.86 OME/Kg with EA vs 2.02 ± 1.92, p < 0.001). There were no differences seen by POD#2. Average pain scores were significantly lower in patients with EA following laparotomy (POD#0-1.22 ± 0.99 with EA vs 1.75 ± 1.33, p = 0.008) and thoracotomy (POD#0-1.71 ± 1.13 with EA vs 2.40 ± 1.52, p = 0.04). CONCLUSIONS: The use of EA in pediatric surgery patients was associated with lower pain scores despite lower systemic opioid requirements in the early post-operative period.

Thoracoscopy vs thoracotomy for the management of metastatic osteosarcoma: A Pediatric Surgical Oncology Research Collaborative Study.

Complete surgical resection of pulmonary metastatic disease in patients with osteosarcoma is crucial to long-term survival. Open thoracotomy allows palpation of nodules not identified on imaging but the impact on survival is unknown. The objective of this study was to compare overall survival (OS) and pulmonary disease-free survival (DFS) in children who underwent thoracotomy vs thoracoscopic surgery for pulmonary metastasectomy. A multi-institutional collaborative group retrospectively reviewed 202 pediatric patients with osteosarcoma who underwent pulmonary metastasectomy by thoracotomy (n = 154) or thoracoscopy (n = 48). Results were analyzed by Kaplan-Meier survival estimates and multivariate Cox proportional hazard regression models. With median follow-up of 45 months, 135 (67.5%) patients had a pulmonary relapse and 95 (47%) patients were deceased. Kaplan-Meier analysis showed no significant difference in 5-year pulmonary DFS (25% vs 38%; P = .18) or OS (49% vs 42%, P = .37) between the surgical approaches of thoracotomy and thoracoscopy. In Cox regression analysis controlling for other factors impacting outcome, there was a significantly increased risk of mortality (HR 2.11; P = .027; 95% CI 1.09-4.09) but not pulmonary recurrence (HR 0.96; P = .90; 95% CI 0.52-1.79) with a thoracoscopic approach. However, in the subset analysis limited to patients with oligometastatic disease, thoracoscopy had no increased risk of mortality (HR 1.16; P = .62; 0.64-2.11). In conclusion, patients with metastatic osteosarcoma and limited pulmonary disease burden demonstrate comparable outcomes after thoracotomy and thoracoscopy for metastasectomy. While significant selection bias in these surgical cohorts limits the generalizability of the conclusions, clinical equipoise for a randomized clinical trial in patients with oligometastatic disease is supported.

Vascular tumors.

Vascular tumors are a rare subset of vascular anomalies. These are classified based on their malignant potential or local destruction potential. Classification has been historically difficult and treatment recommendations are based on case series. The purpose of this chapter is to review the presentation, pathologic and imaging characteristics. Treatment recommendations are summarized based on the current literature. Congenital and infantile hemangiomas are covered separately in a separate chapter in this issue.

Alternative approaches to retroperitoneal lymph node dissection for paratesticular rhabdomyosarcoma.

PURPOSE: The aim of this study was to evaluate outcomes based on surgical approach for retroperitoneal lymph node dissection (RPLND) in patients with paratesticular rhabdomyosarcoma (PT-RMS). METHODS: Patients undergoing RPLND for PT-RMS over 10 years at a single institution were retrospectively reviewed. Length of stay (LOS), complications, oral morphine equivalents per kilogram (OME/Kg), lymph node yield, and time to chemotherapy were assessed. The surgical approaches compared were: open transabdominal, open extraperitoneal, laparoscopic, and retroperitoneoscopic. For cases with lymphatic mapping, indocyanine green (ICG) was injected into the spermatic cord. RESULTS: Twenty patients were included: five open transabdominal, six open extraperitoneal, three laparoscopic, and six retroperitoneoscopic operations. LOS was shorter in the retroperitoneoscopic group than laparoscopic (p = 0.029) and both open groups (p < 0.001). Mean OME/kg used was lowest in the retroperitoneoscopic (0.13 ±â€¯0.15) group compared to laparoscopic (0.68 ±â€¯0.53, p = 0.043), open transabdominal (14.90 ±â€¯8.87, p = 0.003), and extraperitoneal (10.11 ±â€¯2.44, p < 0.001). Time to chemotherapy was shorter for retroperitoneoscopic patients (0.13 days ±â€¯0.15) compared to open transabdominal (15.6 days±6.5, p = 0.005). There was no difference in lymph node yield between groups. Spermatic cord ICG demonstrated iliac lymph node avidity on near-infrared spectroscopy. CONCLUSIONS: Minimally invasive RPLND appears to offer a faster recovery without compromising lymph node yield for patients with PT-RMS. LEVEL OF EVIDENCE: III.

Optimization of percutaneous biopsy for diagnosis and pretreatment risk assessment of neuroblastoma.

BACKGROUND: Image-guided percutaneous core needle biopsy (PCNB) is increasingly utilized to diagnose solid tumors. The objective of this study is to determine whether PCNB is adequate for modern biologic characterization of neuroblastoma. PROCEDURE: A multi-institutional retrospective study was performed by the Pediatric Surgical Oncology Research Collaborative on children with neuroblastoma at 12 institutions over a 3-year period. Data collected included demographics, clinical details, biopsy technique, complications, and adequacy of biopsies for cytogenetic markers utilized by the Children's Oncology Group for risk stratification. RESULTS: A total of 243 children were identified with a diagnosis of neuroblastoma: 79 (32.5%) tumor excision at diagnosis, 94 (38.7%) open incisional biopsy (IB), and 70 (28.8%) PCNB. Compared to IB, there was no significant difference in ability to accurately obtain a primary diagnosis by PCNB (95.7% vs 98.9%, P = .314) or determine MYCN copy number (92.4% vs 97.8%, P = .111). The yield for loss of heterozygosity and tumor ploidy was lower with PCNB versus IB (56.1% vs 90.9%, P < .05; and 58.0% vs. 88.5%, P < .05). Complications did not differ between groups (2.9 % vs 3.3%, P = 1.000), though the PCNB group had fewer blood transfusions and lower opioid usage. Efficacy of PCNB was improved for loss of heterozygosity when a pediatric pathologist evaluated the fresh specimen for adequacy. CONCLUSIONS: PCNB is a less invasive alternative to open biopsy for primary diagnosis and MYCN oncogene status in patients with neuroblastoma. Our data suggest that PCNB could be optimized for complete genetic analysis by standardized protocols and real-time pathology assessment of specimen quality.

Validating an opioid prescribing algorithm in post-operative pediatric surgical oncology patients.

PURPOSE: We developed an algorithm to decrease opioid prescriptions for pediatric oncology patients at discharge following surgery, based on a retrospective analysis to decrease variability and over-prescribing. The aim of this study was to prospectively test the algorithm. METHODS: Opioid-naïve patients undergoing surgery for tumor resection at a single institution were included. A prescribing algorithm was developed based on surgical approach, day of discharge, and inpatient opioid use. Prospectively collected data included outpatient opioid consumption and patient/family satisfaction. Total home dose prescribed was equal to that used in the 8 or 24 h, depending on length of stay and operative approach, prior to discharge, divided into 0.15 mg/kg doses. RESULTS: The algorithm was used in 121 patients and correctly predicted outpatient opioid requirements for 102 patients (84.3%). For 15 (12.4%) patients, the algorithm over-estimated opioid need by an average of 0.38 OME/kg. Four (3.3%) patients required additional opioids. Using this algorithm, we decreased overall opioid prescriptions from 6.17 to 0.21 OME/kg (p < 0.001), and all but one patient/family reported being satisfied with post-operative pain control. CONCLUSION: Using an algorithm based on inpatient opioid use, outpatient opioid needs can be accurately predicted, thereby reducing excess opioid prescriptions without detriment to patient satisfaction. TYPE OF STUDY: Prospective Quality Initiative Study. LEVEL OF EVIDENCE: Level III.

Renal Tumors in Children and Young Adults Older Than 5 Years of Age.

Renal masses are most common in children between ages 1 to 3 years, with less known about renal tumors in older children and young adults. The aim of this study was to review the presentation, demographics, histology, and outcomes in patients over 5 years of age with renal tumors compared with younger children. 111 renal tumors were diagnosed in patients 5 years of age and older (median, 7 y; range, 5 to 31 y) between 1950 and 2017 at a single institution. Wilms tumor (WT) was the most common histology in 84 patients (75%), followed by renal cell carcinoma in 12 patients (10.7%). Abdominal pain was the most common presenting symptom (46%) followed by hematuria (28.8%), and a palpable abdominal mass (24.3%). For WT, older children more commonly presented with advanced-stage disease (stages 3 and 4) than younger children (57.7% vs. 11.5%; P<0.001). Event-free survival (EFS) and overall survival (OS) for favorable histology WT were not different between younger and older children (OS, P=0.43; EFS, P=0.46). In this cohort, older children more frequently present with variable signs and symptoms, less common histopathologies although WT was still most frequent, and more advanced-stage disease compared with younger cohorts, but without differences in EFS or OS.

A Quality Improvement Intervention to Decrease Postoperative Opioid Prescriptions in Pediatric Oncology Patients.

PURPOSE: This quality improvement initiative aimed to minimize opioid prescribing after oncologic pediatric surgery. METHODS: Retrospective surgical data collected at a pediatric cancer hospital from July 2016 to June 2018 included hospitalization details, oral morphine equivalents prescribed, unplanned visits/calls because of pain, and parental/patient satisfaction with pain control. The quality improvement initiative promoted opioid prescription at discharge on the basis of prior inpatient requirements and education regarding nonopioid analgesia. Upon commencing this project in July 2018, we collected data prospectively. RESULTS: The retrospective and the prospective cohorts included 271 and 99 patients, respectively. Mean (SD) oral morphine equivalents (mg/kg) prescribed upon discharge was significantly reduced in the prospective (0.75±1.34) versus retrospective cohorts (5.48±6.94, P<0.001). The unplanned visits/calls regarding pain were 23 (retrospective, 8.5%) and 2 (prospective, 2.0%). In total, 44 patients (44.4%) received an opioid prescription at discharge in the prospective cohort, significantly fewer than retrospective cohort (251, 92.6%, P<0.001), and used a mean of 34.3 of 159.8 (21.5%) doses dispensed. Length of stay was comparable (P=0.88) between cohorts. Prospective satisfaction rate was 96.2%, leaving 3 patients (3.8%) not satisfied with their pain control regimen. CONCLUSIONS: Dramatic reduction of opioid prescriptions after oncologic surgery can be achieved without detriment to patient satisfaction or readmissions. LEVEL OF EVIDENCE: Level V.

Improving Quality of Chest Computed Tomography for Evaluation of Pediatric Malignancies.

INTRODUCTION: Atelectasis is a problem in sedated pediatric patients undergoing cross-sectional imaging, impairing the ability to accurately interpret chest computed tomography (CT) imaging for the presence of malignancy, often leading to additional maneuvers and/or repeat imaging with additional radiation exposure. METHODS: A quality improvement team established a best-practice protocol to improve the quality of thoracic CT imaging in young patients with suspected primary or metastatic pulmonary malignancy. The specific aim was to increase the percentage of chest CT scans obtained for the evaluation of pulmonary nodules with acceptable atelectasis scores (0-1) in patients aged 0-5 years with malignancy, from a baseline of 45% to a goal of 75%. RESULTS: A retrospective cohort consisted of 94 patients undergoing chest CT between February 2014 and January 2015 before protocol implementation. The prospective cohort included 195 patients imaged between February 2015 and April 2018. The baseline percentage of CT scans that were scored 0 or 1 on the atelectasis scale was 44.7%, which improved to 75% with protocol implementation. The mean atelectasis score improved from 1.79 (±0.14) to 0.7 (±0.09). Sedation incidence decreased substantially from 73.2% to 26.5% during the study period. CONCLUSIONS: Using quality improvement methodology including standardization of care, the percentage of children with atelectasis scores of 0-1 undergoing cross-sectional thoracic imaging improved from 45% to 75%. Also, eliminating the need for sedation in these patients has further improved image quality, potentially allowing for optimal detection of smaller nodules, and minimizing morbidity.