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Purpose: To determine whether extent of surgical resection of the primary tumor correlates with survival in patients with International Neuroblastoma Staging System (INSS) stage 4, high-risk neuroblastoma., Methods: Data were extracted for patients with newly diagnosed INSS stage 4, high-risk neuroblastoma between 2001 and 2019 from the national Cancer in Young People in Canada (CYPC) database. Complete resection was defined as gross total resection of primary tumor based on operative reports. Primary endpoints were 3 and 5-year event-free (EFS) and overall survival (OS). Survival analyses were completed using log-rank test and Cox proportional hazards regression including covariates of age, sex, decade of treatment (2001-2009 vs. 2010-2019), immunotherapy, and tandem stem cell transplant (SCT)., Results: One-hundred and forty patients with complete surgical data were included. On univariate analysis, 3-year EFS and OS for patients that had complete versus incomplete resection was 71% (95% CI 57-80%) vs. 48% (36-60%) and 86% (75-93%) vs. 64% (51-74%), p = .008 and p = .002, respectively. 5-year EFS and OS for patients with complete resection also demonstrated significantly improved survival. On Cox Proportional Hazards models adjusted for age, immunotherapy, tandem SCT, and surgical resection, only complete resection was associated with statistically significant improved 3 year EFS and OS, HR = 0.48 (0.29-0.81; p = .006) and HR = 0.42 (0.24-0.73; p = .002)., Conclusions: In a large Canadian INSS stage 4 high-risk neuroblastoma cohort, complete surgical resection was associated with increased EFS and OS. Within the constraints of a retrospective study, these results suggest that the ability to achieve primary tumor complete resection in patients with metastatic high-risk disease is associated with improved survival., (© 2023 Wiley Periodicals LLC.)

The article presents abstracts of studies on pediatrics which include "Neonatal Abstinence Syndrome" by Eric S. Hall et al, "Stool Microbiota and Vaccine Responses of Infants" by M. Nazul Huda et al, and "Socioeconomic Status and Wait Times for Pediatric Surgery in Canada" by Mark Szynkaruk et al.

Introduction: Cancer is the leading cause of disease-related death in children aged 1 to 14 years in Canada. Despite the importance to public health of childhood cancer, there have been few reports on Canadian trends published in the peer-reviewed literature. This study examines childhood cancer trends by age, sex, and province of residence using the most current cancer registration data. Methods: Data from the population-based Canadian Cancer Registry were used to compute incidence trends in primary cancers diagnosed between 1992 and 2006 in children (0-14 years) for the 12 major diagnostic groups of the International Classification of Childhood Cancer, 3rd Edition. Results: Between 1992 and 2006, incidence rates for all cancers remained stable, although trends varied by cancer type. We observed a significant decrease in retinoblastoma in boys for the entire period (-6.5% per year) and an increase in leukemia from 1992 to 1999 ( + 3.5% per year). In girls, there was a significant decrease in renal tumours from 1998 to 2006 (-5.7% per year) and an increase in hepatic tumours from 1997 to 2006 ( + 8.1% per year). Differences by age and province were also apparent. Some caution should be exercised when interpreting trends involving a small number of cases per year and those with wide 95% confidence intervals. Conclusions: Our findings suggest an ongoing need for population-based surveillance and etiologic research. [ABSTRACT FROM AUTHOR]

Paraquat (PQ) is suspected to be an environmental risk factor for Parkinson`s disease (PD). A strong correlation between exposure to paraquat and the occurrence of PD was reported in Canada, Taiwan, and the United States. This correlation is supported by in vivo work showing that paraquat produces dopaminergic pathogenesis. In particular, paraquat forms abnormal protein aggregates in dopaminergic neurons of mice. However, it is not clear how paraquat produces this pathology. Given that proteasome dysfunction induces aberrant protein aggregation, it was hypothesized that paraquat induces proteasome dysfunction. To explore this possibility, proteasome activity and some factors possibly contributing to proteasome dysfunction were investigated in dopaminergic SY5Y cells treated with paraquat. Furthermore, levels of α-synuclein and ubiquitin-conjugated proteins were measured to test whether paraquat induces protein accumulation in SY5Y cells. Results showed that at a concentration of paraquat that reduced viability by about 60% at 48 h (0.5 mM) loss of proteasome activity occurred. In addition, the cells showed decreased ATP levels and reduced mitochondrial complex V activity. These changes were significant 24 h after treatment with paraquat. Furthermore, paraquat-treated cells showed decreased protein levels of proteasome 19S subunits, but not 20S α or β subunits, suggesting that the effects observed were not the result of general cytotoxicity. Paraquat also increased levels of α-synuclein and ubiquitinated proteins, suggesting that paraquat-induced proteasome dysfunction leads to aberrant protein accumulation. Taken together, these findings support the hypothesis that paraquat impairs proteasome function in SY5Y cells. [ABSTRACT FROM AUTHOR]

Purpose: The origin of congenital abdominal cysts in the female fetus often dictates management. While most arise from the ovary and are often managed non-operatively, some are non-ovarian and are frequently removed. We analyzed a national sample of female infants with congenital abdominal cysts to elucidate prenatal and postnatal factors associated with the diagnosis of a non-ovarian cyst., Methods: A retrospective cohort study of female infants who were prenatally diagnosed with abdominal cysts between 2013 and 2017 at 10 Canadian pediatric surgical centres was performed. Clinical characteristics, pre- and postnatal sonographic findings, and cyst trajectories were compared between patients with proven ovarian etiology and those with cysts arising from other organs., Results: Of 185 infants with prenatally diagnosed abdominal cysts, 22 (12%) were non-ovarian, five of which had clear non-ovarian organ of origin on prenatal ultrasound. Comparison of the other 17 cysts with 163 congenital ovarian cysts showed the following factors to be associated with a non-ovarian origin: earlier gestational age at diagnosis (23.5 vs 33.5 weeks, p <0.001), smaller diameter on first prenatal ultrasound (15.8 vs. 39.7 mm, p <0.001), change in sonographic character from simple to complex (87% vs 22%, p <0.001), and postnatal sonographic characteristics of complex cyst (87% vs. 48%, p = 0.004)., Conclusion: Clear organ of origin, diagnosis earlier in gestation, smaller initial prenatal cyst diameter, and sonographic cyst character change differentiate congenital non-ovarian cysts from their ovarian counterparts. These characteristics may be used to guide diagnosis and management., (Copyright © 2022. Published by Elsevier Inc.)

Abstract. A large neuroblastoma screening study was recently started in the province of Quebec, Canada. This project, a collaboration between the Quebec Network for Genetic Medicine and the University of Minnesota, is studying the impact of screening infants for the preclinical detection of neuroblastoma on the population-based mortality caused by this tumor. All infants born in Quebec during a 5-year period will be screened twice, at 3 weeks and at 6 months. Urinary homovanillic acid and vanillylmandelic acid determination from dried filter paper samples is used for screening. Initial qualitative screening is done by means of thin-layer chromatography with confirmatory quantitative screening by gas chromatography-mass spectrometry (GC-MS). During the initial 6 months of 3-week screening, 41 673 neonates (92% compliance rate) were screened and 10.6% of them were tested also by GC-MS. Nine of these neonates had positive results on two GC-MS tests and were referred for evaluation to rule out the presence of neuroblastoma. Four had the tumor, I had a calcified adrenal gland, and 4 had no tumor detected. Three additional neonates had clinical diagnosis of neuroblastoma before they reached the screening age of 3 weeks. A neuroblastoma that did not secrete homovanillic acid or vanillylmandelic acid was diagnosed clinically in 1 additional patient who tested negative by screening. [ABSTRACT FROM AUTHOR]

The incidence and mortality of neuroblastoma was reviewed in the general context of childhood cancer in Canada for the periods 1982-86 and 1987-91. This was done to complement the preliminary work of the Quebec Neuroblastoma Screening Project that is studying the impact of screening North American infants for the preclinical detection of neuroblastoma on population-based mortality. Annual age-standardized incidence rates for all childhood cancer in Canada appear to have declined slightly (nonsignificantly) from 155.1 to 150.8 per million, between 1982-86 and 1987-91; the rates for neuroblastoma were stable between the two five-year periods (11.8 per million in 1982-86 and 11.4 per million in 1987-91). With respect to mortality, the age-standardized rates for childhood cancer in Canada have shown a declining trend between the first and second halves of the decade, from 43.4 to 34.7 per million, while the rates for neuroblastoma have not changed (4.4 and 4.2 per million). The age-specific distributions of incident cancers indicate that neuroblastoma accounts for the greatest proportion of all cancers in children less than one year of age. Similarly, neuroblastoma is the leading cause of cancer deaths in children aged one to four years. Theoretically, infants less than one year of age could benefit most from effective preventive interventions, treatment, and research. [ABSTRACT FROM AUTHOR]

Background and Objectives: A 2-year-old female with neuroblastoma needed In(b-), E- red blood cells (RBCs). No units were available at the blood centre (BC) nor in the rare donor programme member's inventories. BC's Immunohematology Reference Laboratory (IRL) and its marketing department concentrated on recruiting and testing those donors more likely to be antigen negative based on ethnicity., Materials and Methods: The BC's communication plan utilized social and traditional media to assist in the search for In(b-) blood. Media strategies directed donors in the United States (US) and Canada to go to their nearest BC for collection, tagging and testing of units. Two segments from each donation were shipped overnight to the BC's IRL (associated with the patient) for testing. Diluted anti-Inb sera was tested by microtechniques to conserve resources. Additionally, the American Rare Donor Program (ARDP) facilitated the international searches and acted as a liaison to the Food and Drug Administration (FDA)., Results: More than 25 000 people responded to the appeal. Seventy-seven BCs submitted segments from 4197 units. Two donors were In(b-) but E+ and thus not compatible with the patient but were submitted to ARDP for future needs. The prevalence of In(b-) units identified in the search was 0·048%. In total, five known In(b-) donors, two from the US and three from international sources, provided units for this patient., Conclusion: Social media sparked a viral response to the rare blood need. While a match was not found among the units tested, domestic and international searches were able to meet the patient's blood needs., (© 2020 International Society of Blood Transfusion.)

Background: nab-Paclitaxel has demonstrated efficacy in adults with solid tumours and preclinical activity in paediatric solid tumour models. Results from phase I of a phase I/II study in paediatric patients with recurrent/refractory solid tumours treated with nab-paclitaxel are reported., Patients and Methods: Patients with recurrent/refractory extracranial solid tumours received nab-paclitaxel on days 1, 8 and 15 every 4 weeks at 120, 150, 180, 210, 240, or 270 mg/m 2 (rolling-6 dose-escalation) to establish the maximum tolerated dose (MTD) and recommended phase II dose (RP2D)., Results: Sixty-four patients were treated. Dose-limiting toxicities were grade 3 dizziness at 120 mg/m 2 and grade 4 neutropenia >7 days at 270 mg/m 2 . The most frequent grade 3/4 adverse events were haematologic, including neutropenia (36%), leukopenia (36%) and lymphopenia (25%). Although the MTD was not reached, 270 mg/m 2 was declared non-tolerable due to grade 3/4 toxicities during cycles 1-2 (neutropenia, n = 5/7; skin toxicity, n = 2/7; peripheral neuropathy, n = 1/7). Of 58 efficacy-evaluable patients, complete response occurred in one patient (2%; Ewing sarcoma) and partial responses in four patients (7%; rhabdomyosarcoma, Ewing sarcoma, renal tumour with pulmonary metastases [high-grade, malignant] and sarcoma not otherwise specified); all responses occurred at ≥210 mg/m 2 . Thirteen patients (22%) had stable disease (5 lasting ≥16 weeks) per RECIST., Conclusions: nab-Paclitaxel 240 mg/m 2 qw3/4 (nearly double the adult recommended monotherapy dose for this schedule in metastatic breast cancer) was selected as the RP2D based on the tolerability profile, pharmacokinetics and antitumour activity. Phase II is currently enrolling patients with recurrent/refractory neuroblastoma, rhabdomyosarcoma and Ewing sarcoma. CLINICALTRIALS.GOV: NCT01962103., Eudract: 2013-000144-26., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The article discusses the strategy of mass screening for neuroblastoma in children. Because of the ease of the screening test through catecholamine metabolite measurement and also due to the fact that early presenters of neuroblastoma have a better prognosis, there seemed to be logic to performing mass screening in children. The author concludes, however, based on studies in Quebec, Canada and in Germany, that screening is not only without value, but may even cause damage.