Stage 4N neuroblastoma before and during the era of anti-GD2 immunotherapy.

Patients with stage 4N neuroblastoma (distant metastases limited to lymph nodes) stand out as virtually the only survivors of high-risk neuroblastoma (HR-NB) before myeloablative therapy (MAT) and immunotherapy with anti-GD2 monoclonal antibodies (mAbs) became standard. Because no report presents more recent results with 4N, we analyzed our large 4N experience. All 51 pediatric 4N patients (<18 years old) diagnosed 1985 to 2021 were reviewed. HR-NB included MYCN-nonamplified 4N diagnosed at age ≥18 months and MYCN-amplified 4N. Among 34 MYCN-nonamplified high-risk patients, 20 are relapse-free 1.5+ to 37.5+ (median 12.5+) years post-diagnosis, including 13 without prior MAT and 5 treated with little (1 cycle; n = 2) or no mAb (n = 3), while 14 patients (7 post-MAT, 8 post-mAbs) relapsed (all soft tissue). Of 15 MYCN-amplified 4N patients, 7 are relapse-free 2.1+ to 26.4+ (median 11.6+) years from the start of chemotherapy (all received mAbs; 3 underwent MAT) and 4 are in second remission 4.2+ to 21.8+ years postrelapse (all soft tissue). Statistical analyses showed no significant association of survival with either MAT or mAbs for MYCN-nonamplified HR-NB; small numbers prevented these analyses for MYCN-amplified patients. The two patients with intermediate-risk 4N (14-months-old) are relapse-free 7+ years postresection of primary tumors; distant disease spontaneously regressed. The natural history of 4N is marked by NB confined to soft tissue without early relapse in bones or bone marrow, where mAbs have proven efficacy. These findings plus curability without MAT, as seen elsewhere and at our center, support consideration of treatment reduction for MYCN-nonamplified 4N.

Magnetic Resonance-Guided High Intensity Focused Ultrasound Generated Hyperthermia: A Feasible Treatment Method in a Murine Rhabdomyosarcoma Model.

Magnetic resonance-guided high intensity focused ultrasound (MRgHIFU) is an established method for producing localized hyperthermia. Given the real-time imaging and acoustic energy modulation, this modality enables precise temperature control within a defined area. Many thermal applications are being explored with this noninvasive, nonionizing technology, such as hyperthermia generation, to release drugs from thermosensitive liposomal carriers. These drugs can include chemotherapies such as doxorubicin, for which targeted release is desired due to the dose-limiting systemic side effects, namely cardiotoxicity. Doxorubicin is a mainstay for treating a variety of malignant tumors and is commonly used in relapsed or recurrent rhabdomyosarcoma (RMS). RMS is the most common solid soft tissue extracranial tumor in children and young adults. Despite aggressive, multimodal therapy, RMS survival rates have remained the same for the past 30 years. To explore a solution for addressing this unmet need, an experimental protocol was developed to evaluate the release of thermosensitive liposomal doxorubicin (TLD) in an immunocompetent, syngeneic RMS mouse model using MRgHIFU as the source of hyperthermia for drug release.

Advances in the treatment of pediatric solid tumors: A 50-year perspective.

In the United States, more than 10 000 cancers occur annually in children aged 0-14 years, and more than 5000 in adolescents aged 15-19. In the last 50 years, significant advances have been made in imaging, molecular pathology, stage and risk assessment, surgical approach, multidisciplinary treatment, and survival for pediatric solid tumors (particularly neuroblastoma, Wilms tumor, rhabdomyosarcoma, and hepatoblastoma). Moreover, the molecular driver for fibrolamellar hepatocellular carcinoma, which occurs in adolescence and young adulthood, has been identified.

International Society of Paediatric Surgical Oncology (IPSO) Surgical Practice Guidelines.

Most children with tumors will require one or more surgical interventions as part of the care and treatment, including making a diagnosis, obtaining adequate venous access, performing a surgical resection for solid tumors (with staging and reconstruction), performing procedures for cancer prevention and its late effects, and managing complications of treatment; all with the goal of improving survival and quality of life. It is important for surgeons to adhere to sound pediatric surgical oncology principles, as they are closely associated with improved local control and survival. Unfortunately, there is a significant disparity in survival rates in low and middle income countries, when compared to those from high income countries. The International Society of Paediatric Surgical Oncology (IPSO) is the leading organization that deals with pediatric surgical oncology worldwide. This organization allows experts in the field from around the globe to gather and address the surgical needs of children with cancer. IPSO has been invited to contribute surgical guidance as part of the World Health Organization Initiative for Childhood Cancer. One of our goals is to provide surgical guidance for different scenarios, including those experienced in High- (HICs) and Low- and Middle-Income Countries (LMICs). With this in mind, the following guidelines have been developed by authors from both HICs and LMICs. These have been further validated by experts with the aim of providing evidence-based information for surgeons who care for children with cancer. We hope that this initiative will benefit children worldwide in the best way possible. Simone Abib, IPSO President Justin T Gerstle, IPSO Education Committee Chair Chan Hon Chui, IPSO Secretary.

Prospective pan-cancer germline testing using MSK-IMPACT informs clinical translation in 751 patients with pediatric solid tumors.

The spectrum of germline predisposition in pediatric cancer continues to be realized. Here we report 751 solid tumor patients who underwent prospective matched tumor-normal DNA sequencing and downstream clinical use (clinicaltrials.gov NCT01775072). Germline pathogenic and likely pathogenic (P/LP) variants were reported. One or more P/LP variants were found in 18% (138/751) of individuals when including variants in low, moderate, and high penetrance dominant or recessive genes, or 13% (99/751) in moderate and high penetrance dominant genes. 34% of high or moderate penetrance variants were unexpected based on the patient's diagnosis and previous history. 76% of patients with positive results completed a clinical genetics visit, and 21% had at least one relative undergo cascade testing as a result of this testing. Clinical actionability additionally included screening, risk reduction in relatives, reproductive use, and use of targeted therapies. Germline testing should be considered for all children with cancer.

Comprehensive Molecular Profiling of Desmoplastic Small Round Cell Tumor.

Desmoplastic small round cell tumor (DSRCT) is characterized by the EWSR1-WT1 t(11;22) (p13:q12) translocation. Few additional putative drivers have been identified, and research has suffered from a lack of model systems. Next-generation sequencing (NGS) data from 68 matched tumor-normal samples, whole-genome sequencing data from 10 samples, transcriptomic and affymetrix array data, and a bank of DSRCT patient-derived xenograft (PDX) are presented. EWSR1-WT1 fusions were noted to be simple, balanced events. Recurrent mutations were uncommon, but were noted in TERT (3%), ARID1A (6%), HRAS (5%), and TP53 (3%), and recurrent loss of heterozygosity (LOH) at 11p, 11q, and 16q was identified in 18%, 22%, and 34% of samples, respectively. Comparison of tumor-normal matched versus unmatched analysis suggests overcalling of somatic mutations in prior publications of DSRCT NGS data. Alterations in fibroblast growth factor receptor 4 (FGFR4) were identified in 5 of 68 (7%) of tumor samples, whereas differential overexpression of FGFR4 was confirmed orthogonally using 2 platforms. PDX models harbored the pathognomic EWSR1-WT1 fusion and were highly representative of corresponding tumors. Our analyses confirm DSRCT as a genomically quiet cancer defined by the balanced translocation, t(11;22)(p13:q12), characterized by a paucity of secondary mutations but a significant number of copy number alterations. Against this genomically quiet background, recurrent activating alterations of FGFR4 stood out, and suggest that this receptor tyrosine kinase, also noted to be highly expressed in DSRCT, should be further investigated. Future studies of DSRCT biology and preclinical therapeutic strategies should benefit from the PDX models characterized in this study. IMPLICATIONS: These data describe the general quiescence of the desmoplastic small round cell tumor (DSRCT) genome, present the first available bank of DSRCT model systems, and nominate FGFR4 as a key receptor tyrosine kinase in DSRCT, based on high expression, recurrent amplification, and recurrent activating mutations.

11p15.5 epimutations in children with Wilms tumor and hepatoblastoma detected in peripheral blood.

BACKGROUND: Constitutional or somatic mosaic epimutations are increasingly recognized as a mechanism of gene dysregulation resulting in cancer susceptibility. Beckwith-Wiedemann syndrome is the cancer predisposition syndrome most commonly associated with epimutation and is extremely variable in its phenotypic presentation, which can include isolated tumors. Because to the authors' knowledge large-scale germline DNA sequencing studies have not included methylation analysis, the percentage of pediatric cancer predisposition that is due to epimutations is unknown. METHODS: Germline methylation testing at the 11p15.5 locus was performed in blood for 24 consecutive patients presenting with hepatoblastoma (3 patients) or Wilms tumor (21 patients). RESULTS: Six individuals with Wilms tumor and 1 patient with hepatoblastoma were found to have low-level gain of methylation at imprinting control 1, and a child with hepatoblastoma was found to have loss of methylation at imprinting control 2. The loss of methylation at imprinting control 2 was found to be maternally inherited, despite not being associated with any detectable genomic alteration. CONCLUSIONS: Overall, 33% of patients (8 of 24 patients) with Wilms tumor or hepatoblastoma were found to have an epigenetic susceptibility that was detectable in the blood. It is interesting to note that low-level gain of methylation at imprinting control 1 predominantly was detected in females with bilateral Wilms tumors. Further studies in larger cohorts are needed to determine the efficacy of testing all patients with Wilms tumor or hepatoblastoma for 11p15.5 epimutations in the blood as part of DNA analysis because this hallmark of predisposition will not be detected by sequencing-based approaches and detecting a cancer predisposition may modify treatment.

Magnetic Resonance-guided High-intensity Focused Ultrasound (MRgHIFU) Virtual Treatment Planning for Abdominal Neuroblastoma Utilizing Retrospective Diagnostic 3D CT Images.

Magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) is a novel treatment for neuroblastoma using ultrasound-induced thermal ablation with real-time MR thermometry. It is unclear which patients would be amenable to MRgHIFU given the retroperitoneal location of many neuroblastomas within the smaller pediatric abdomen. In addition, planning relies on MR scans, which are not routine in the standard pediatric neuroblastoma workup. This study sought to demonstrate that neuroblastomas are targetable with MRgHIFU and available computed tomographic imaging could be utilized for MRgHIFU virtual treatment. Cross-sectional images of 88 pediatric abdominal neuroblastoma patients were retrospectively processed with custom software to be made compatible with the Sonalleve MRgHIFU platform. Targetability measured percent treatment to lesion volume, within adequate safety margins from critical structures. All images were successfully converted into treatment planning files. Median lesion size was 191±195 cm and depth was 29±17 mm. Up to 78 (85%) patients had targetable lesions with a median targetable volume of 15% and ranging up to 79%. Targetability was highest in superficial, right upper quadrant lesions >200 cm, but limited by proximity to bowel and ribs. This study demonstrates the capacity for MRgHIFU to potentially treat the majority of abdominal neuroblastomas and the feasibility of using computed tomographic images for MRgHIFU virtual treatment planning.

Multifocal hepatoblastoma: What is the risk of recurrent disease in the remnant liver?

PURPOSE: Multifocal hepatoblastoma (HB) is often treated with total hepatectomy and transplantation owing to concerns of surgical resectability, local recurrence, and/or metachronous tumor in the remnant liver. We aimed to review HB patients to determine the risk of local recurrence in multifocal disease. METHODS: We undertook retrospective cohort analysis of all HB patients at a single tertiary referral center between 2001 and 2015. Demographics, diagnostic features, operative details, and outcomes were analyzed. RESULTS: Sixty patients underwent surgical management of HB. 39 had unifocal, and 21 had multifocal disease. Of multifocal patients, 9 underwent liver transplantation, 10 anatomic resections, and 2 nonanatomic resections. Overall, two patients had recurrence in the remnant liver - both from the unifocal group. There were equivalent distant (lung) recurrences between the groups (8% for unifocal versus 14% for multifocal), p = 0.89. At a mean of 75 months of follow-up, overall survival was 97% for unifocal patients and 86% for multifocal patients, p = 0.12. CONCLUSION: Multifocal HB was not associated with increased local recurrence in the setting of R0 resection and chemotherapy. These data do not support the contention that all patients with multifocal HB require a total hepatectomy and transplantation to reduce the incidence of local recurrence and/or metachronous tumor development. LEVEL OF EVIDENCE: Level III - Limited cohort analysis.

Refining How We Define Laparoscopic Expertise.

BACKGROUND: Traditional stratification of expertise in laparoscopic simulation assigns participants to novice, intermediate, or expert groups based on case numbers. We hypothesized that expert video assessment might refine this discrimination of psychomotor expertise, especially in light of new measurable parameters. MATERIALS AND METHODS: One hundred five participants performed a defined intracorporeal suturing task in the pediatric laparoscopic surgery simulator armed with force-sensing capabilities. Participants were stratified into novice, intermediate, and expert groups via three classification schemes: (1) number of complex laparoscopic cases, (2) self-declared level of expertise, and (3) average expert rating of participants' videos. Precision, time to task completion, and force analysis parameters (FAP = total, maximum and mean forces in three axes) were compared using one-way analysis of variance tests. P < .05 was considered significant. RESULTS: Participants stratified on the basis of case numbers and on the basis of self-declared level of expertise had statistically significant differences in time to task completion, but no significant difference in FAP. When participants were restratified according to expert assessment of their video performance, time to task completion as well as total and mean forces in X, Y, and Z axes allowed discrimination between novices, intermediates, and experts, thus establishing construct validity for the latter. Precision did not allow discrimination in any stratification scheme. CONCLUSION: Compared with traditional stratification, video assessment allows refined discrimination of psychomotor expertise within a simulator. Assessment of FAP may become a relevant tool for teaching and assessing laparoscopic skills.

Long term outcomes after concurrent ipsilateral nephrectomy versus kidney-sparing surgery for high-risk, intraabdominal neuroblastoma.

PURPOSE: The impact of the extent of surgical resection including nephrectomy for high-risk neuroblastoma patients is controversial. In this study, we compared the renal late effects and long-term survival for patients who underwent kidney-sparing surgery (KSS) versus concurrent ipsilateral nephrectomy (CIN) for high-risk, intraabdominal neuroblastoma (HRIN). METHODS: A retrospective analysis of patients diagnosed with HRIN between Jan 1998 and Dec 2008 in a tertiary referral center was performed. Demographics, preoperative features, surgical resection extent and outcomes were analyzed. RESULTS: Of 58 patients who underwent surgical management of HRIN, 6 underwent CIN and 52 underwent KSS. Renal image-defined risk factors (IDRFs) were more common in patients who underwent CIN. Operating time was longer and EBL higher in CIN patients. There was no difference in recurrence or overall survival between the groups. Estimated GFR (eGFR) was comparable between the groups preoperatively, but was reduced postoperatively and at long-term follow-up in patients who underwent CIN. CONCLUSION: Compared to KSS, CIN is not associated with an increase in local recurrence or inferior survival but does lead to reduced kidney function (eGFR of 90 ml/min/1.73 m2 for CIN versus 127 ml/min/1.73 m2 for KSS, p = 0.03) but without significant impact on clinical outcome. LEVELS OF EVIDENCE: III (Retrospective comparative study).

Laparoscopic Revision of Ventriculoperitoneal Shunts in Pediatric Patients May Result in Fewer Subsequent Peritoneal Revisions.

INTRODUCTION: Ventriculoperitoneal shunts (VPSs) are the mainstay of treatment of hydrocephalus but frequently need revision. We sought to directly compare the impact of laparoscopic versus open peritoneal shunt revision on the need for subsequent VPS revisions in pediatric patients. MATERIALS AND METHODS: A prospectively maintained, externally validated database of pediatric patients who underwent a first peritoneal VPS revision at a single center between 2008 and 2016 was reviewed. Outcomes, including subsequent revisions, shunt infections, operative time, and hospital stay between open and laparoscopic groups, were compared. RESULTS: A total of 148 patients underwent a first peritoneal VPS revision during the time period-40 laparoscopically and 108 open-with no significant difference in age or gender between the groups. Operative time, length of stay after shunt revision, and shunt infection rates did not vary between laparoscopic versus open revisions. There was no significant difference between need for subsequent overall (peritoneal or ventricular) shunt revisions in the laparoscopic (20%) versus the open group (34%), P = .07. However, there were significantly fewer frequent peritoneal revisions in the laparoscopic group (3% versus 15%, P = .04). CONCLUSIONS: This first cohort analysis of laparoscopic versus open VPS revision in pediatric patients suggests that laparoscopic peritoneal VPS revision may reduce the rate of subsequent peritoneal revisions without increasing shunt infections or operative time in pediatric patients.

Laparoscopic insertion of ventriculoperitoneal shunts in pediatric patients - A retrospective cohort study.

INTRODUCTION: Ventriculoperitoneal shunts (VPSs) are the mainstay of treatment of hydrocephalus but have frequent complications including shunt failure and infection. There has been no comparison of laparoscopic versus open primary VPS insertion in children. We hypothesized that laparoscopic VP shunt insertion may improve patient outcomes. METHODS: A prospectively-maintained, externally-validated database of pediatric patients who underwent VPS insertion at a single center between 2012 and 2016 was reviewed. Outcomes including subsequent revisions, shunt infections, operative time, and hospital stay between open and laparoscopic groups were compared. RESULTS: 210 patients underwent VPS insertion - 41 laparoscopically and 169 open. Operative time was longer for laparoscopic insertions. There was no difference in shunt infections, complications or length of stay. There was no difference between overall revisions or in confirmed peritoneal obstructions in the laparoscopic (12%) versus open VPS insertions (5%), p = 0.13. CONCLUSIONS: This first cohort analysis of laparoscopic versus open VPS insertion in pediatric patients indicates no difference in confirmed peritoneal obstructions. With increasing use of laparoscopic placement in some centers, it remains important to elucidate if there is a subset of pediatric patients who might benefit from this technique; possible candidates may be those who are overweight/obese or have had previous intra-abdominal surgery. LEVEL OF EVIDENCE: III - Retrospective cohort study.

The Heterogeneity of Global Pediatric Surgery: Defining Needs and Opportunities Around the World.

BACKGROUND: The global burden of pediatric surgical conditions continues to remain inadequately addressed, particularly in low- and middle-income countries. Among the many factors contributing to this gap are a lack of access to care secondary to resource shortages and inequitable distribution, underfinancing of healthcare systems, poor quality of care, and contextual challenges such as natural disasters and conflict. The relative contribution of these and other factors varies widely by region and even with countries of a region. METHODS: This review seeks to discuss the heterogeneity of global pediatric surgery and offer recommendations for addressing the barriers to high-quality pediatric surgical care throughout the world. RESULTS: There is significant heterogeneity in pediatric surgical challenges, both between regions and among countries in the same region, although data are limited. This heterogeneity can reflect differences in demographics, epidemiology, geography, income level, health spending, historical health policies, and cultural practices, among others. CONCLUSION: Country-level research and stakeholder engagement are needed to better understand the heterogeneity of local needs and drive policy changes that contribute to sustainable reforms. Key to these efforts will be improved financing, access to and quality of pediatric surgical care.

Refinement in the analysis of motion within low-cost laparoscopic simulators of differing size: Implications on assessing technical skills.

BACKGROUND: Simulation is becoming more important in the teaching and assessment of technical skills. The purpose of this study was to refine the use of motion analysis parameters (MAPs) to assess performance of a defined task in low-cost pediatric laparoscopic simulators of differing size. METHODS: 105 participants performed a defined intracorporeal suturing task in large and small pediatric laparoscopic simulators. Outcomes included MAPs - path length, extreme velocity events, and extreme acceleration events in all available degrees of freedom for novices, intermediates, and experts. ANOVA p <0.05 was judged significant. RESULTS: In the smaller simulator, all MAPs discriminated between expertise groups in all degrees of freedom. In the larger simulator, all but one MAP discriminated between expertise groups. Experts demonstrated the greatest variability in performance between the larger and smaller simulators. CONCLUSION: Analysis of motion in the performance of a defined intracorporeal suturing task allowed discrimination between novices, intermediates, and experts in large and small low-cost pediatric laparoscopic simulators. Further refinement in MAPs will determine their role in surgical education. LEVEL OF EVIDENCE: Not applicable.

The Impact of Simulator Size on Forces Generated in the Performance of a Defined Intracorporeal Suturing Task: A Pilot Study.

Background: In pediatric minimal access surgery, the operative domain may vary from that of an adult to that of a neonate. This study aimed to quantify the impact of decreased operative domain on forces generated in the performance of a defined intracorporeal suturing task. Methods: One hundred five participants performed a defined intracorporeal suturing task in small and large simulators. Time to task completion and force analysis parameters (FAPs = total, maximum, and mean forces in X, Y, and Z axes) were measured. Expertise level was assigned based on the number of laparoscopic cases. Outcomes were analyzed using paired sample t-tests, P value of <.05. Results: Time to task completion varied significantly for experts between adult and pediatric simulators but not for intermediates or novices. Total, maximum, and mean forces in the X ("side to side") axis were significantly greater in the larger laparoscopic simulator for all levels of expertise. In the Y axis ("in and out" movement) and Z axis ("up and down" movement), total and mean forces were higher in the adult simulator regardless of the level of expertise. Differences in maximum force between the adult and pediatric simulators in the Z axis ("up and down" movement) varied significantly for novices and intermediates but not for experts. Conclusion: Forces were greater, particularly in the side-to-side plane, in the larger simulator for participants of all levels in the performance of this defined intracorporeal suturing task. Further analysis will determine the reasons for and implications of the increased force parameters in the simulator of larger domain.

Development of an Open-Source Laparoscopic Simulator Capable of Motion and Force Assessment: High Tech at Low Cost.

OBJECTIVE: Laparoscopic simulators help improve surgical skills in an ex vivo setting. New simulators incorporate force and motion assessment, but often at high financial cost. Our goal is to establish global access to a laparoscopic simulator, which offers both traditional summative assessment (time to task completion and precision) as well as advanced formative assessment (force and motion sensing capabilities) so that educators anywhere may be able to create simulators with increased educational value. DESIGN: A low-cost laparoscopic simulator incorporating an off-the-shelf optical sensor, inertial measurement unit, holders, and a housing unit for a microcontroller was integrated into a plastic box with a high-definition digital camera and a three-dimensional mouse. Open source software was developed to offer real-time feedback in force and motion. The system was calibrated for accuracy and consistency. RESULTS: The simulator was assembled from off-the-shelf components and open-source software. Total estimated cost was $350 United States Dollars. The mouse was calibrated by applying known forces in known directions. Linear forces measured in all axes showed linear output trends with r2-values of between 0.988 and 0.999. Accuracy in motion evaluation was evaluated and this demonstrated low average errors in the motion sensors of 5.4% to 6.8%. CONCLUSIONS: This low-cost, off-the-shelf, open-access laparoscopic simulator provides accurate and consistent measures of force and motion. We believe that collaborative efforts between surgeons and engineers can allow the creation of these surgical teaching devices at a reasonable cost such that they can be used in resource-rich and resource-limited settings.

Pediatric Gastrointestinal Posttransplant Lymphoproliferative Disorder: Incidence, Clinical Characteristics, and Impact of Major Surgical Interventions Upon Overall Survival.

Posttransplant lymphoproliferative disorder (PTLD) is a severe complication of solid organ transplantation. A common site for PTLD development is the gastrointestinal (GI) tract. The purpose of this study was to evaluate the incidence, clinical features, and overall survival of pediatric patients with GI-PTLD, and to assess whether major surgical interventions increased mortality. Records of pediatric transplant patients who developed GI-PTLD between January 2000 and June 2015 were retrospectively reviewed at our institution. Of 814 patients who received solid organ transplants, 34 (4%) developed GI-PTLD. Lung and multiorgan transplants had the highest incidence of GI-PTLD (both 11%). Patients often had multisite GI involvement (47%). Within the first year of transplantation, 38% of the 34 patients developed GI-PTLD. Of the patients with Epstein-Barr Virus-positive disease, 12/22 (55%) presented in the first 12 months of transplantation, compared with only 1/12 (8%) of the patients with Epstein-Barr Virus-negative disease (P=0.002). Major surgical interventions were required in 41% of patients; overall survival rate for these surgical patients was 71%, compared with 60% for patients not requiring major surgical interventions (P=0.49). Despite multimodal treatments, overall survival remains poor for patients with GI-PTLD; however, major surgical intervention did not significantly impact overall survival in this cohort.

Aggressive embryonal rhabdomyosarcoma in a 3-month-old boy: A clinical and molecular analysis.

Rhabdomyosarcoma (RMS) represents the most common soft tissue sarcoma in the pediatric age group. While RMS has been traditionally classified on the basis of its histological appearance (with embryonal and alveolar being most common), it is now clear that the PAX-FOXO1 fusion product drives prognosis. We report here a case of pelvic embryonal RMS in a 3-month-old male who was subsequently found to have developed brain metastases during the course of chemotherapy. Cytogenetic analysis of the brain metastases at the time of autopsy as well as next-generation sequencing analysis revealed a reciprocal translocation involving the SH3 domain containing ring finger 3 gene (SH3RF3, on chromosome 2q13) and the Lipase C gene (LIPC, on chromosome 15q21.3). Due to the poor quality of the pretreatment and postresection samples, cytogenetics and NGS analysis looking for the presence of this balanced translocation in these specimens could not be performed. To the authors' knowledge, this translocation has never been described in RMS. Further studies are needed to determine the biological and clinical implications of this novel translocation.

Educational Role for an Advanced Suturing Task in the Pediatric Laparoscopic Surgery Simulator.

BACKGROUND: Laparoscopic models are recognized as important training tools. Lower fidelity systems are used mainly for simpler tasks; an advanced suturing task may allow for additional training of experts. The purpose of this study was to explore the educational role of an advanced suturing task using motion analysis and establish the task's construct validity. METHODS: The pediatric laparoscopic surgery (PLS) simulator was customized with motion-tracking hardware and software. Participants were stratified by expertise, then performed an advanced task involving intracorporeal suturing in a vertical plane, with the suture passing superiorly to inferiorly. Traditional PLS scores were calculated, and motion was analyzed in the four degrees of freedom available in laparoscopic surgery (Pitch, Yaw, Roll, and Surge). Data were compared to historic results for a standard suturing task. RESULTS: Sixty participants were recruited (8 novices, 13 intermediates, and 39 experts). Analysis of motion in all degrees of freedom allowed discrimination between participants based on expertise level. Compared with the standard task, PLS scores for the advanced task were significantly lower for intermediates and experts, and the number of extreme motion events was significantly higher, indicating that advanced task is more challenging. In addition, only 76.3% of experts, 76.9% of intermediates, and 37.5% of novices were able to successfully complete the advanced task. CONCLUSIONS: Performance of an advanced intracorporeal suturing task allowed discrimination of expertise level. The task's increased complexity may help hone laparoscopic technical skills, particularly among advanced performers, and even allow discrimination of psychomotor expertise within the traditional cohort of experts.