Dual-labeled anti-GD2 targeted probe for intraoperative molecular imaging of neuroblastoma.

BACKGROUND: Surgical resection is integral for the treatment of neuroblastoma, the most common extracranial solid malignancy in children. Safely locating and resecting primary tumor and remote deposits of disease remains a significant challenge, resulting in high rates of complications and incomplete surgery, worsening outcomes. Intraoperative molecular imaging (IMI) uses targeted radioactive or fluorescent tracers to identify and visualize tumors intraoperatively. GD2 was selected as an IMI target, as it is highly overexpressed in neuroblastoma and minimally expressed in normal tissue. METHODS: GD2 expression in neuroblastoma cell lines was measured by flow cytometry. DTPA and IRDye® 800CW were conjugated to anti-GD2 antibody to generate DTPA-αGD2-IR800. Binding affinity (Kd) of the antibody and the non-radiolabeled tracer were then measured by ELISA assay. Human neuroblastoma SK-N-BE(2) cells were surgically injected into the left adrenal gland of 3.5-5-week-old nude mice and the orthotopic xenograft tumors grew for 5 weeks. 111In-αGD2-IR800 or isotype control tracer was administered via tail vein injection. After 4 and 6 days, mice were euthanized and gamma and fluorescence biodistributions were measured using a gamma counter and ImageJ analysis of acquired SPY-PHI fluorescence images of resected organs (including tumor, contralateral adrenal, kidneys, liver, muscle, blood, and others). Organ uptake was compared by one-way ANOVA (with a separate analysis for each tracer/day combination), and if significant, Sidak's multiple comparison test was used to compare the uptake of each organ to the tumor. Handheld tools were also used to detect and visualize tumor in situ, and to assess for residual disease following non-guided resection. RESULTS: 111In-αGD2-IR800 was successfully synthesized with 0.75-2.0 DTPA and 2-3 IRDye® 800CW per antibody and retained adequate antigen-binding (Kd = 2.39 nM for aGD2 vs. 21.31 nM for DTPA-aGD2-IR800). The anti-GD2 tracer demonstrated antigen-specific uptake in mice with human neuroblastoma xenografts (gamma biodistribution tumor-to-blood ratios of 3.87 and 3.88 on days 4 and 6 with anti-GD2 tracer), while isotype control tracer did not accumulate (0.414 and 0.514 on days 4 and 6). Probe accumulation in xenografts was detected and visualized using widely available operative tools (Neoprobe® and SPY-PHI camera) and facilitated detection ofputative residual disease in the resection cavity following unguided resection. CONCLUSIONS: We have developed a dual-labeled anti-GD2 antibody-based tracer that incorporates In-111 and IRDye® 800CW for radio- and fluorescence-guided surgery, respectively. The tracer adequately binds to GD2, specifically accumulates in GD2-expressing xenograft tumors, and enables tumor visualization with a hand-held NIR camera. These results encourage the development of 111In-αGD2-IR800 for future use in children with neuroblastoma, with the goal of improving patient safety, completeness of resection, and overall patient outcomes.

Image-guided core-needle or surgical biopsy for neuroblastoma diagnosis in children: A systematic review and meta-analysis from the International Society of Pediatric Surgical Oncology (IPSO).

BACKGROUND: Image-guided core-needle biopsy (IGCNB) is a widely used and valuable clinical tool for tissue diagnosis of pediatric neuroblastoma. However, open surgical biopsy remains common practice even if children undergo more invasive and painful procedures. This review aims to determine the diagnostic accuracy and safety of IGCNBs in pediatric patients with neuroblastoma. METHODS: We conducted a systematic review of peer-reviewed original articles published between 1980 and 2023, by searching "pediatric oncology," "biopsy," "interventional radiology," and "neuroblastoma." Exclusion criteria were patients older than 18 years, studies concerning non-neurogenic tumors, case reports, and language other than English. Both the systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RESULTS: A total of 533 abstracts articles were analyzed. Of these, eight retrospective studies met inclusion criteria (490 infants, 270 surgical biopsies [SB], 220 image-guided biopsies). Tissue adequacy for primary diagnosis (SB: n = 265, 98%; IGCNB: n = 199, 90%; p = .1) and biological characterization (SB: n = 186, 95%; IGCNB: n = 109, 89%; p = .15) was similar with both biopsy techniques, while intraoperative transfusion rate (SB: n = 51, 22%; IGCNB: n = 12, 6%; p = .0002) and complications (%) (SB: n = 58, 21%; IGCNB: n = 14, 6%; p = .005) were higher with surgical biopsy. Length of stay was similar in both groups; however, no additional data about concurrent diagnostic or treatment procedures were available in the analyzed studies. CONCLUSIONS: IGCNB is a safe and effective strategic approach for diagnostic workup of NB and should be considered in preferance to SB wherever possible.

A subset of image-defined risk factors predict completeness of resection in children with high-risk neuroblastoma: An international multicenter study.

BACKGROUND: Image-defined risk factors (IDRFs) were promulgated for predicting the feasibility and safety of complete primary tumor resection in children with neuroblastoma (NB). There is limited understanding of the impact of individual IDRFs on resectability of the primary tumor or patient outcomes. A multicenter database of patients with high-risk NB was interrogated to answer this question. DESIGN/METHODS: Patients with high-risk NB (age <20 years) were eligible if cross-sectional imaging was performed at least twice prior to resection. IDRFs and primary tumor measurements were recorded for each imaging study. Extent of resection was determined from operative reports. RESULTS: There were 211 of 229 patients with IDRFs at diagnosis, and 171 patients with IDRFs present pre-surgery. A ≥90% resection was significantly more likely in the absence of tumor invading or encasing the porta hepatis, hepatoduodenal ligament, superior mesenteric artery (SMA), renal pedicles, abdominal aorta/inferior vena cava (IVC), iliac vessels, and/or diaphragm at diagnosis or an overlapping subset of IDRFs (except diaphragm) at pre-surgery. There were no significant differences in event-free survival (EFS) and overall survival (OS) when patients were stratified by the presence versus absence of any IDRF either at diagnosis or pre-surgery. CONCLUSION: Two distinct but overlapping subsets of IDRFs present either at diagnosis or after induction chemotherapy significantly influence the probability of a complete resection in children with high-risk NB. The presence of IDRFs was not associated with significant differences in OS or EFS in this cohort.

Tracking changes in image-defined risk factors during neoadjuvant chemotherapy and their predictive value for surgical outcomes based on the International Neuroblastoma Surgical Report Form.

BACKGROUND: The capacity of presurgical image-defined risk factors (IDRFs) to predict secondary surgical outcomes in patients with neuroblastoma is controversial. METHODS: The International Neuroblastoma Surgical Report Form (INSRF) was employed to retrospectively collect the clinical data of 53 patients diagnosed with neuroblastoma at our hospital from April 2014 to April 2020. IDRFs were identified at the time of diagnosis and reassessed during the course of neoadjuvant chemotherapy. Various statistical tests were used to evaluate the correlation between IDRFs and secondary surgical outcomes. RESULTS: A total of 195 IDRFs were identified. Notably, by two courses of neoadjuvant chemotherapy, the number of "two body compartments," "intraspinal tumor extension," and "trachea-compressing" IDRFs decreased significantly (p = .001). The primary tumor volumes and the number of IDRFs decreased significantly by four courses of neoadjuvant chemotherapy, especially in "intraspinal tumor extension" IDRFs (p = .034). The median number of IDRF per patient was four (interquartile range [IQR]: 1-5) at diagnosis, which diminished to one (IQR: 1-3) subsequent to neoadjuvant chemotherapy. The presence of preoperative IDRFs was not associated with surgical complications (p = .286) or the extent of surgery (p = .188). However, the number of preoperative IDRFs linked to the extent of surgery (p = .002), not to operative complications (p = .669). Specifically, presurgery "renal vessel contact" IDRFs were predictive of surgical complications, while presurgery "infiltration of vital structures" IDRFs were associated with the extent of surgery. CONCLUSION: The number of IDRFs decreased significantly by four courses of neoadjuvant chemotherapy. The number and type of presurgery IDRFs may predict secondary surgical outcomes, surpassing the mere consideration of their presence or absence.

Decoding pediatric spinal tumors: a single-center retrospective case series on etiology, presentation, therapeutic strategies, and outcomes.

INTRODUCTION: Spinal tumors (ST) often result in dire prognosis, carrying risks such as permanent paralysis, sensory loss, and sphincter dysfunction. Data on their incidence and etiology in pediatric populations are markedly scant. Our study investigates the etiology, clinical manifestation, treatment, and outcomes of pediatric ST. METHODS: We conducted a retrospective review of our institutional pediatric oncology and neurosurgery database, examining 14 patients under 18 years admitted with ST due to oncological diseases since 2005. We analyzed the clinical presentations, evaluations, molecular diagnostics and treatments for these patients. RESULTS: The study spanned 15 years and included 14 pediatric patients, each diagnosed with distinct spinal tumor entity. The mean patient age was approximately 19.6 ± 10.1 months. Severe axial pain along the vertebral column was observed in 13 patients, while acute neurological deterioration manifested in 7 patients. As a first-line intervention, 13 patients underwent decompressive surgery through laminectomy and tumor resection, and only one patient received chemotherapy solely. Before surgery, seven patients were unable to walk; post-surgery, six of them regained their ability to ambulate. The diagnosis encompassed a range of neoplasms: two instances of Ewing sarcoma, 3 instances of teratoma, one case presenting an atypical teratoid Rhabdoid tumor, two instances each of low-grade astrocytoma and neuroblastoma, and single instances of ependymoma, meningioma, rhabdomyosarcoma, and embryonal tumors with multilayered rosettes (ETMRs). Three patients succumbed two years after initiating therapy. CONCLUSION: Despite their rarity, intraspinal tumors in pediatric patients pose substantial therapeutic challenges. The intertwined complexities of the disease entity and the patient's neurological status demand swift initiation of an individualized therapeutic strategy. This crucial step helps optimize outcomes for this patient cohort, who frequently grapple with debilitating health conditions. Inclusion of these patients within a registry is mandatory to optimize treatment outcomes due to their rarity in pediatric population.

Successful endoscopic approach for peripheral neuroblastic tumors in children.

BACKGROUND: Recently, reports of endoscopic approaches for neuroblastoma, ganglioneuroblastoma, and ganglioneuroma (peripheral neuroblastic tumor; PNTs) have been increasing. This study aimed to clarify the indications for endoscopic surgery for PNTs. METHODS: Pediatric patients who underwent endoscopic surgery for PNTs at our institution were included in this study. Image-defined risk factors (IDRFs) were analyzed using preoperative computed tomography (CT). RESULTS: Twenty-four patients underwent endoscopic surgery for PNTs. The diagnoses included neuroblastoma (n = 11), ganglioneuroma (n = 10), and ganglioneuroblastoma (n = 3). Regarding the tumor site, there were 18 cases of adrenal tumors, five cases of mediastinal tumors, and one case of retroperitoneal tumors. Image-defined risk factors were positive in eight cases (contacted with a renal vessel, n = 6; compression of principal bronchi, n = 2). Complete resection was accomplished in 21 cases (14 of 16 IDRF-negative cases and seven of eight IDRF-positive cases). All patients survived without recurrence during the follow-up period. CONCLUSIONS: The CT findings of contact with renal vessels and compression of principal bronchi do not seem to be indicators of incomplete resection. An endoscopic approach to PNTs in pediatric patients is feasible with a good prognosis if patients are selected strictly.

Incidental finding of atrial myxoma following curative treatment for paediatric neuroblastoma.

Cardiac tumours are uncommon in the general population and even more so in the paediatric population. Here we present a case of an asymptomatic 7-year-old male with history of high-risk neuroblastoma who underwent 1-year post-treatment surveillance scan with an incidental finding of intracardiac lesion found to be an atrial myxoma.

Cadaveric analysis of surgical techniques and working space for retroperitoneal tumors as model for improving resection of neuroblastoma.

PURPOSE: Neuroblastoma, the most common extracranial solid tumor in children under 5 years, often surrounds visceral arteries. This study aimed to analyze the working space provided by standardized surgical techniques at key arterial landmarks in adult cadavers. METHODS: We assessed in eight adult cadavers the mobilization of the left colon, spleen and pancreas, right colon, duodenum and mesenteric root, access to the bursa omentalis. The average working space score (AWSS) was evaluated at the left and right renal artery, left and right side of the coeliac trunk, superior mesenteric and common hepatic artery. The score was defined as: (0) vessel not visible, (1) working space at the vessel ≤ 1x diameter of the aorta, (2) < 3x the diameter of the aorta, (3) ≥ 3x diameter of the aorta. RESULTS: The maximum AWSS of 3 was achieved at key vascular landmarks through specific mobilization techniques. CONCLUSION: Additional mobilization of spleen, pancreas and mesenteric root and access to the bursa omentalis increase surgical working space at major visceral arteries. The results of our investigation provide surgeons with a useful guide to prepare for abdominal neuroblastoma resection.

Risk factors, impact and treatment of postoperative lymphatic leakage in children with abdominal neuroblastoma operated on by laparotomy.

BACKGROUND: Lymphatic leakage is one of the postoperative complications of neuroblastoma. The purpose of this study is to summarize the clinical characteristics and risk factors of lymphatic leakage and try to find effective prevention and treatment measures. METHODS: A retrospective study included 186 children with abdominal neuroblastoma, including 32 children of lymphatic leakage and 154 children of non-lymphatic leakage. The clinical information, surgical data, postoperative abdominal drainage, treatment of lymphatic leakage and prognosis of the two groups were collected and analyzed. RESULTS: The incidence of lymphatic leakage in this cohort was 14% (32 children). Through univariate analysis of lymphatic leakage group and non-lymphatic leakage group, we found that lymphatic leakage increased the complications, prolonged the time of abdominal drainage and hospitalization, and delayed postoperative chemotherapy (p < 0.05). In this cohort, the median follow-up time was 46 (95% CI: 44-48) months. The follow-up data of 7 children were partially missing. 147 children survived, of which 23 had tumor recurrence (5 children recurred in the surgical area). 37 children died, of which 32 had tumor recurrence (9 children recurred in the operation area). In univariate analysis, there was no statistical difference in overall survival (p = 0.21) and event-free survival (p = 0.057) between lymphatic leakage group and non-lymphatic leakage group, while 3-year cumulative incidence of local progression was higher in lymphatic leakage group (p = 0.015). However, through multivariate analysis, we found that lymphatic leakage did not affect event-free survival, overall survival and cumulative incidence of local progression in children with neuroblastoma. Resection of 5 or more lymphatic regions was an independent risk factor for lymphatic leakage after neuroblastoma surgery. All 32 children with lymphatic leakage were cured by conservative treatment without surgery. Of these, 75% (24/32) children were cured by fat-free diet or observation, 25% (8/32) children were cured by total parenteral nutrition. The median drain output at diagnosis in total parenteral nutrition group was higher than that in non-total parenteral nutrition group (p < 0.001). The cut-off value was 17.2 ml/kg/day. CONCLUSIONS: Lymphatic leakage does not affect the prognosis of children with neuroblastoma, but long-term drain output caused by lymphatic leakage will still adversely affect postoperative complications and follow-up treatment, which requires attention and active treatment measures. More attention should be paid to the children with 5 or more lymphatic regions resection, and the injured lymphatic vessels should be actively found and ligated after tumor resection to reduce the postoperative lymphatic leakage. Early application of total parenteral nutrition is recommended for those who have drain output at diagnosis of greater than 17.2 ml/kg/day. LEVEL OF EVIDENCE: Level III, Treatment study (Retrospective comparative study).

Percutaneous core needle biopsy of neuroblastoma in the pediatric population: what have we learned in the last decade.

INTRODUCTION: Historically, neuroblastoma has been diagnosed by surgical open biopsy (SB). In recent decades, core needle biopsy (CNB) has replaced surgical biopsy due to its safe and adequate method of obtaining tissue diagnosis. AIM: Our study aimed to assess the effectiveness of CNB in obtaining tissue diagnosis for neuroblastoma and evaluate its safety profile in terms of post-operative complications, in comparison to SB. METHODS: A retrospective cohort study, including all patients younger than 18 years who were diagnosed with neuroblastoma from 2012 until 2022 in a single tertiary medical center. Patients' demographics, tumor size and location, pathological results, and clinical outcomes were collected. RESULTS: 79 patients were included in our study: 35 biopsies were obtained using image-guided CNB and 44 using SB. Patients' and tumor characteristics including age, gender, tumor volume, and stage were similar in both groups. The biopsy adequacy rate in the CNB group was 91% and 3 patients in this group underwent repeated biopsy. The safety profile in the CNB group was similar to the SB group. CONCLUSIONS: CNB is a safe method and should be considered the first choice for obtaining tissue diagnosis when feasible due to its high adequacy in terms of tumor histopathological features.

[Autologous kidney transplantation in a high-risk patient with locally advanced retroperitoneal neuroblastoma]. / Autologicheskaya transplantatsiya pochki u patsienta s mestnorasprostranennoi neiroblastomoi zabryushinnogo prostranstva gruppy vysokogo riska. Klinicheskoe nablyudenie.

Surgery of locally advanced neuroblastoma with risk factors is one of the most difficult in pediatric surgery. Incidence of nephrectomy during subtotal or complete tumor resection is higher due to common involvement of renal vessels. We present a patient with locally advanced retroperitoneal neuroblastoma who underwent heterotopic kidney autotransplantation.

[Surgery for abdominal neuroblastoma in children]. / Khirurgiya neiroblastomy abdominal'noi lokalizatsii u detei.

This review is devoted to surgical approach for neurogenic tumors in children. The authors discuss epidemiological data, history of surgical approaches, preoperative imaging and risk factors. A special attention is paid to the influence of surgical interventions for various neuroblastomas on overall and event-free survival in pediatric population, as well as the most common surgical complications and modern approaches to their treatment.

Relationship between the timing of chemotherapy and surgical complications following surgical biopsy in children with malignant solid tumors.

BACKGROUND: Biopsies for diagnosis before chemotherapy is common in children with malignant solid tumors. Wound healing is delayed by chemotherapy; however, the ideal interval between biopsy and chemotherapy remains unknown. We aimed to summarize the relationship between chemotherapy timing and postoperative surgical complications. PROCEDURE: We retrospectively reviewed patients with malignant solid tumors who underwent chemotherapy after surgical biopsy at our institution between January 2014 and August 2020. The primary outcomes were postoperative surgical complications (within 30 days) and the timing of chemotherapy. RESULTS: Forty-three patients were analyzed. The types of tumors were neuroblastoma (n = 20), hepatoblastoma (n = 10), Ewing sarcoma (n = 5), germ cell tumor (n = 3), angiosarcoma (n = 1), clear cell sarcoma (n = 1), ganglioneuroblastoma (n = 1), rhabdoid tumor (n = 1), and rhabdomyosarcoma (n = 1). The operative procedures were thoracoscopy (n = 5), laparotomy (n = 17), laparoscopy (n = 14), and superficial (n = 7). The median time [range] to chemotherapy after biopsy was 4 [0-21] days. No surgical complications occurred before chemotherapy, and two (4.7%) patients experienced complications after chemotherapy. These included postoperative hemorrhage (grade 3) and surgical site infection (grade 1). Chemotherapy was initiated 1 and 6 days after biopsy, respectively, in these cases. Complications occurred 10 and 23 days after biopsy, respectively. CONCLUSION: The rate of postoperative surgical complications related to biopsy seems acceptable, even when chemotherapy was initiated in the early postoperative period. Early initiation of chemotherapy after biopsy may be a suitable option, particularly in children with bulky or symptomatic malignant solid tumors.

Image-defined risk factors in localized thoracic neuroblastoma and ganglioneuroma.

BACKGROUND: The pretreatment International Neuroblastoma Risk Group Staging System (INRGSS) discriminates localized tumors L1/L2 depending on the absence/presence of image-defined risk factors (IDRFs) at diagnosis. Referring to this new staging system, we assessed initial imaging of localized thoracic neuroblastoma (NB) and ganglioneuroma (GN) and the extent of initial tumor resection. METHODS: Patients with localized thoracic NB/GN from the German clinical trials NB97 and NB2004 were included. Imaging at diagnosis and operative reports were reviewed retrospectively. IDRFs were assessed centrally and correlated to International Neuroblastoma Staging System (INSS) stage and extent of tumor resection. Additionally, we analyzed data on surgery-related complications. RESULTS: Imaging series of 88 patients were available for central review. In 18 children, no IDRF was present, 28 exhibited one IDRF, 42 two or more IDRFs, resulting in 70 patients with L2 disease. The most frequently observed IDRF was encasement of any vessel (n = 38). Initial surgical resection was aimed for in 45 patients (L1: n = 11; L2: n = 34). Complete and gross total resection rates were higher children with L2 NB (n = 8/25 L1, n = 17/25 L2 vs. n = 2/15 L1, n = 13/15 L2, respectively). The proportion of surgical complications was very similar between INRGSS L1 and L2 (n = 4/11 vs. n = 17/34). All complications were manageable, and no surgery-related deaths were observed. CONCLUSION: In this retrospective cohort, the extent of resection and the rate of surgical complications did not differ substantially between patients classified as L1/L2, indicating that INRGSS L2 does not equate unresectability. It appeared that individual IDRFs differ in value. Larger studies are needed to assess the significance and therapeutic/prognostic impact of such findings.

Perioperative hypertension and anesthetic management in patients undergoing resection of neuroblastoma.

INTRODUCTION: Neuroblastoma is the most common extracranial pediatric tumor, accounting for 5-8% of all childhood cancers. Neuroblastomas arise from catecholamine-secreting neural crest cells and their metabolites, vanillylmandelic acid and homovanillic acid, that are readily detected in urine. Although rarely seen in clinical practice, case reports exist documenting severe intraoperative hypertension. However, data on the incidence of intraoperative hypertension are lacking. METHODS: This report is a single-center retrospective review of patients with neuroblastoma who underwent surgical resection (n = 102) at Boston Children's Hospital from July 1, 2012 to February 28, 2021. Significant intraoperative hypertension was defined as maximum systolic blood pressure greater than 95th percentile +12 mmHg based on normative blood pressure data. Statistical analysis was performed using Fisher's exact test, Wilcoxon rank-sum test, and logistic regression. RESULTS: The overall incidence of intraoperative hypertension was 13% (n = 13/102). Higher American Society of Anesthesiologists (ASA) physical status was associated with intraoperative hypertension. Antihypertensive medications were administered intraoperatively in 9% of cases (n = 9), and the use was significantly associated with intraoperative hypertension. Of patients with preoperative urine catecholamine data (n = 82), all 10 patients who had intraoperative hypertension were noted to have elevated preoperative urine catecholamines. Intraoperative hypertension was not associated with postoperative hypertension, postoperative hypotension, or increased intensive care unit length of stay. DISCUSSION/CONCLUSION: Intraoperative hypertension in patients with neuroblastoma remains a relatively uncommon occurrence; however, it does occur at a frequency higher than previously described. While intraoperative hypertension is associated with an increased use of antihypertensive medications in the operating room, it is not associated with adverse perioperative outcomes.

Safety and feasibility of laparoscopic resection of abdominal neuroblastoma without image-defined risk factors: a single-center experience.

OBJECTIVE: To explore the criteria, safety and efficacy of laparoscopic surgery in pediatric neuroblastoma (NB). METHODS: A retrospective study of 87 patients with NB without image-defined risk factors (IDRFs) between December 2016 and January 2021 at Beijing Children's Hospital was conducted. Patients were divided into two groups according to the surgical procedure. RESULTS: Between the 87 patients, there were 54 (62.07%) cases in the open surgery group and 33 (37.93%) cases in the laparoscopic surgery group. There were no significant differences between the two groups regarding demographic characteristics, genomic and biological features, operating time or postoperative complications. However, in terms of intraoperative bleeding (p = 0.013) and the time to start postoperative feeding after surgery (p = 0.002), the laparoscopic group was obviously better than the open group. Furthermore, there was no significant difference in the prognosis between the two groups, and no recurrence or death was observed. CONCLUSION: For children with localized NB who have no IDRFs, laparoscopic surgery could be performed safely and effectively. Surgeons who are skilled in this can help children reduce surgical injuries, speed up postoperative recovery, and obtain the same prognosis as open surgery.

Beyond image defined risk factors (IDRFs): a delphi survey highlighting definition of the surgical complexity index (SCI) in neuroblastoma.

PURPOSE: Preoperative evaluation of Image Defined Risk Factors (IDRFs) in neuroblastoma (NB) is crucial for determining suitability for upfront resection or tumor biopsy. IDRFs do not all carry the same weighting in predicting tumor complexity and surgical risk. In this study we aimed to assess and categorize a surgical complexity (Surgical Complexity Index, SCI) in NB resection. METHODS: A panel of 15 surgeons was involved in an electronic Delphi consensus survey to identify and score a set of shared items predictive and/or indicative of surgical complexity, including the number of preoperative IDRFs. A shared agreement included the achievement of at least 75% consensus focused on a single or two close risk categories. RESULTS: After 3 Delphi rounds, agreement was established on 25/27 items (92.6%). A severity score was established for each item ranging from 0 to 3 with an overall SCI range varying from a minimum score of zero to a maximum score of 29 points for any given patient. CONCLUSIONS: A consensus on a SCI to stratify the risks related to neuroblastoma tumor resection was established by the panel experts. This index will now be deployed to critically assign a better severity score to IDRFs involved in NB surgery.

Retroperitoneal localized neuroblastoma in children: a comparison of enhanced recovery after surgery versus traditional care.

PURPOSE: To investigate the clinical value of enhanced recovery after surgery (ERAS) protocols for children with neuroblastoma (NB). METHODS: This retrospective review was conducted by using the electronic medical records of 48 children with retroperitoneal localized NB who underwent tumor resection (surgery for treatment, not diagnosis) between October 2016 and September 2021. The ERAS protocols for NB excision were implemented in 28 children (ERAS group), while 20 children received traditional care (TRAD group). The same group of pediatric surgeons performed all the tumor resections. Intraoperative fluid infusion, the extent of NB resection, time of early ambulation and time of first flatus, time to total enteral nutrition (TEN) after surgery, abdominal drainages, nasogastric tubes and urinary catheters used and duration, the Face/Legs/Activity/Cry/Consolability (FLACC) quantitative table on a postoperative day 1 (POD1), 3, 5, length of stay after surgery (LOS), hospitalization expense, postoperative complications, parental satisfaction rate and readmission rate of surgical wards within 30 days after operation were analyzed. RESULTS: The median postoperative period of early mobilization, first flatus, TEN, LOS and total cost during hospitalization were 1.0 days, 2.0 days, 5.5 days, 9.0 days and 33,397.3 yuan in the ERAS group and 3.0 days, 3.0 days, 7.0 days, 11.0 days and 38,120.3 Yuan in the TRAD group, respectively (all p < 0.05). Median intraoperative fluid volume was 5.0 mL/kg/h compared to 8.0 mL/kg/h and the magnitude of decrease in FLACC scores from POD1 to POD5 was greater in the ERAS group (all p < 0.05). Abdominal drainages, urinary catheters and nasogastric tubes were removed earlier in the ERAS group (p < 0.05). The satisfaction of parents in the ERAS group was slightly higher, but the difference was not statistically significant (P = 0.762). There were no marked differences between the two groups in aspects of the extent of NB resection, operation-related complications and 30-day readmissions (all P = 1.000). CONCLUSIONS: Application of ERAS protocols in localized retroperitoneal NBs resection in children is feasible and safe. However, applying ERAS protocols in the surgical resection of solid tumors in children still requires much more research, especially randomized prospective research.

Feasibility and safety of laparoscopic tumor resection in children with abdominal neuroblastomas.

PURPOSE: This study aimed to evaluate the feasibility and safety of laparoscopic resection of abdominal neuroblastoma by comparing operative and long-term oncologic outcomes between open and laparoscopic surgeries. METHODS: This single-center retrospective study included patients who underwent laparoscopic tumor resection, between January 2000 and June 2021, with a maximum tumor diameter of ≤ 60 mm and without image-defined risk factors (IDRFs) at surgery. Data from 35 abdominal neuroblastoma resections were reviewed and compared between the laparotomy and laparoscopic groups. RESULTS: Nineteen patients underwent laparotomy and 16 had laparoscopic tumor resection. All laparoscopic surgeries achieved complete resection without conversion to open surgery. Median blood loss was significantly lower in the laparoscopic group (0.6 mL/kg) than in the laparotomy group (8.4 mL/kg) (P < 0.0001). There were two locoregional recurrences in the laparoscopic group and two metastatic recurrences in the laparotomy group. Five-year overall survival was 93.8% in both groups. CONCLUSION: Laparoscopic resection of abdominal neuroblastomas in children is a feasible and safe procedure for tumors ≤ 60 mm in diameter with no IDRFs at surgery, with long-term outcomes equivalent to laparotomy.

A nomogram for the preoperative estimation of neuroblastoma risk despite inadequate biopsy information.

BACKGROUND AND PURPOSE: If the preoperative pathological information is inadequate, a risk classification may not be able to be determined for some patients with neuroblastoma. Our objectives were to include imaging factors, serum biomarkers, and demographic factors in a nomogram to distinguish high-risk patients before surgical resection based on the COG classification. METHOD: A total of 106 patients were included in the study. Of these, patients with clinicopathologically confirmed neuroblastoma at Tianjin Children's Hospital from January 2013 to November 2021 formed the training cohort (n = 82) for nomogram development, and those patients from January 2010 to December 2013 formed the validation cohort (n = 24) to confirm the model's performance. RESULT: On multivariate analysis of the primary cohort, independent factors for high risk were the presence of distant metastasis (p = 0.004), lactate dehydrogenase (LDH) (p = 0.009), and tumor volume (p = 0.033), which were all selected into the nomogram. The calibration curve for probability showed good agreement between prediction by nomogram and actual observation. The C-index of the nomogram was 0.95 95% [0.916-0.99]. Application of the nomogram in the validation cohort still gave good discrimination and good calibration. CONCLUSION: Three independent factors including the presence of distant metastasis, lactate dehydrogenase (LDH), and tumor volume are associated with high-risk neuroblastoma and selected into the nomogram. The novel nomogram has the flexibility to apply a clinically suitable cutoff to identify high-risk neuroblastoma patients despite inadequate preoperative pathological information. The nomogram can allow these patients to be offered suitable induction chemotherapy regimens and surgical plans. LEVELS OF EVIDENCE: Level III.