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Pediatric bowel obstruction after intra-abdominal cancer surgery is relatively frequent. Few publications have specifically addressed this significant complication. The purpose of this study was to assess the frequency, etiology and treatment options of bowel obstructions following abdominal cancer surgery in children using our institutional database.We retrospectively analyzed a single tertiary pediatric hospital database over a 10-year period. The clinical characteristics of patients with and without bowel obstruction were compared using bivariate analyses. The details of the conservative and operative management of bowel obstructions were evaluated.Out of 130 eligible patients, 18 (13.8%) developed bowel obstruction in a mean follow-up of 5.7 years. Patients who developed bowel obstruction were more likely to have received preoperative radiation therapy (16.7 vs 2.7%, p = 0.036) and had longer operative time (398 vs 268 min, p = 0.022). Non-operative management was successful in 39% of patients (7/18). When patients needed surgical intervention, minimally invasive approach was attempted and successfully performed in 36% of cases (4/11), none of which required conversion to laparotomy nor presented with recurrent bowel obstruction.Bowel obstruction is a frequent complication after abdominal cancer surgery in children. Conservative management is frequently successful. For patients requiring surgical treatment, laparoscopy remains a valuable option and should be considered in selected cases.

Acetaminophen is one of the oldest medications commonly administered in children. Its efficacy in treating fever and pain is well accepted among clinicians. However, the available evidence supporting the use of acetaminophen's different modes of administration remains relatively scarce and poorly known. This short report summarizes the available evidence and provides a framework to guide clinicians regarding a rational use of acetaminophen in children.

The aim of this study was to establish the feasibility and safety of the use of indocyanine green technology during pediatric intestinal resections. While indocyanine green fluorescence angiography (ICG-FA) has been advocated as an imaging technique to assess bowel perfusion in adults, few studies have evaluated this technology in a pediatric context.A prospective clinical trial was conducted. Patients 16 years old or younger undergoing a surgery potentially requiring an intestinal resection were eligible. Patients received a standardized intravenous injection of indocyanine green and intestinal perfusion was evaluated. The study endpoints included safety, impact on bowel resection and feasibility and acceptance of ICG-FA in this population.From May 2020 to March 2021, 30 consecutive patients were included in this trial. Final analysis was done on 28 patients with a median age of 15.00 [6.36,85.00] weeks and weight of 5.58 [3.64,11.70] kg at surgery. Adequate fluorescence was achieved in less than one minute for all cases with an average dose of 0.14 mg/kg. No adverse event related to indocyanine green occurred. ICG-FA versus standard assessment of potential resection sites differed in 62% (95% IC 0.41-0.82) of our cases. Qualitative analysis demonstrated that 95% of the surgical team agreed that ICG-FA was safe.The use of ICG-FA is feasible and safe for pediatric intestinal resections. Introduction of ICG-FA was simple and acceptance rates were high within the surgical team. This fluorescence imaging may be a valuable imaging technology for intestinal resections in pediatric surgery.

The International Society for the Study of Vascular Anomalies (ISSVA) classification distinguishes between common lymphatic malformations and complex lymphatic anomalies. These entities have overlapping features but differing responses to treatment. Surgery has been the mainstream treatment in intra-abdominal lymphatic malformation, with variable reported success in the literature. The aim of this study was to review the outcome of different treatments for intra-abdominal lymphatic malformations in children. We retrospectively reviewed all intra-abdominal lymphatic malformations from 1999 to 2019 in children treated by the surgical team or followed in the vascular anomalies clinic of our institution. Children were classified into one of three groups: group A, isolated intra-abdominal lymphatic malformation; group B, common lymphatic malformation in continuity with other regions; or group C, intra-abdominal involvement as part of a complex lymphatic anomaly or associated syndrome. Fifty intra-abdominal lymphatic malformations were diagnosed; five of these were excluded. In group A (n=28), the treatment was surgical resection (n=26) or sclerosing treatment (n=1), with one case of spontaneous regression; no recurrence was observed in 25 patients. In group B (n=7), three patients had partial resection and all had recurrence; four had sclerotherapy alone with good response. In group C (n=10), therapeutic options included surgery, sclerosing treatment and pharmacotherapy, with variable outcomes. The management of intra-abdominal malformations requires a team approach. Sclerotherapy is successful in treating macrocystic lymphatic malformation. Surgery is successful in treating isolated intra-abdominal common lymphatic malformation, albeit at times at the cost of intestinal resection, which could be avoided by combining surgery with preoperative sclerotherapy. With surgery there is often limited resectability, and therefore recurrence in intra-abdominal lymphatic malformations that are part of complex lymphatic anomalies associated with syndromes, or in common lymphatic malformations in continuity with other regions. Sclerotherapy is an effective modality in these instances along with pharmacotherapy.

Inflammatory myofibroblastic tumor (IMT) is a mesenchymal neoplasm of intermediate malignancy. We describe the largest cohort of IMT patients to date, aiming to further characterize this rare, poorly understood tumor. This is a multi-institutional review of IMT patients ≤39 years, from 2000 to 2018, at 18 hospitals in the Pediatric Surgical Oncology Research Collaborative. One hundred and eighty-two patients were identified with median age of 11 years. Thirty-three percent of tumors were thoracic in origin. Presenting signs/symptoms included pain (29%), respiratory symptoms (25%) and constitutional symptoms (20%). Median tumor size was 3.9 cm. Anaplastic lymphoma kinase (ALK) overexpression was identified in 53% of patients. Seven percent of patients had distant disease at diagnosis. Ninety-one percent of patients underwent resection: 14% received neoadjuvant treatment and 22% adjuvant treatment. Twelve percent of patients received an ALK inhibitor. Sixty-six percent of surgical patients had complete resection, with 20% positive microscopic margins and 14% gross residual disease. Approximately 40% had en bloc resection of involved organs. Median follow-up time was 36 months. Overall 5-year survival was 95% and 5-year event-free survival was 80%. Predictors of recurrence included respiratory symptoms, tumor size and distant disease. Gross or microscopic margins were not associated with recurrence, suggesting that aggressive attempts at resection may not be warranted.

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 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 2008-2017 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 (IQR = 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 posterior rib 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 following 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.

We conducted a multi-centre study to assess treatments and outcomes in a national cohort of infants with congenital ovarian cysts.Wide variability exists in the treatment of congenital ovarian cysts. The effects of various treatment strategies on outcomes, specifically ovarian preservation, are not known.Female infants diagnosed with congenital intra-abdominal cysts between 2013-2017 at 10 Canadian pediatric surgical centres were retrospectively evaluated. Sonographic characteristics, median time to cyst resolution, incidence of ovarian preservation, and predictors of surgery were evaluated. Subgroup analyses were performed in patients with complex cysts and cysts ≥40 mm in diameter.The study population included 189 neonates. Median gestational age at diagnosis and median maximal prenatal cyst diameter were 33 weeks and 40 mm, respectively. Cysts resolved spontaneously in 117 patients (62%), 14 (7%) prenatally and the remainder at a median age of 124 days. Intervention occurred in 61 patients (32%), including prenatal aspiration (2, 3%), ovary-sparing resection (14, 23%) or oophorectomy (45, 74%). Surgery occurred at a median age of 7.4 weeks. Independent predictors of surgery included postnatal cyst diameter ≥ 40 mm (OR 6.19, 95% CI 1.66 - 35.9) and sonographic complex cyst character (OR 63.6, 95% CI 10.9 - 1232). There was no significant difference in the odds of ovarian preservation (OR 3.06, 95% CI 0.86 - 13.2) between patients who underwent early surgery (n = 22) and those initially observed for at least 3 months (n = 131).Most congenital ovarian cysts are asymptomatic and spontaneously resolve. Early surgical intervention does not increase ovarian preservation.

Wilms tumor (WT) is the most common renal malignancy in children. Children with favorable histology WT achieve survival rates of over 90%. Twelve percent of patients present with metastatic disease, most commonly to the lungs. The presence of a pleural effusion at the time of diagnosis of WT may be noted on staging imaging; however, minimal data exist regarding the significance and prognostic importance of this finding. The objectives of our study are to identify the incidence of pleural effusions in patients with WT, and to determine the potential impact on oncologic outcomes. A multi-institutional retrospective review was performed from January 2009 to December 2019, including children with WT and a pleural effusion on diagnostic imaging treated at Pediatric Surgical Oncology Research Collaborative (PSORC) participating institutions. Of 1259 children with a new WT diagnosis, 94 (7.5%) had a pleural effusion. Patients with a pleural effusion were older than those without (median 4.3 vs 3.5 years; P = .004), and advanced stages were more common (local stage III 85.9% vs 51.9%; P .0001). Only 14 patients underwent a thoracentesis for fluid evaluation; 3 had cytopathologic evidence of malignant cells. Event-free and overall survival of all children with WT and pleural effusions was 86.2% and 91.5%, respectively. The rate and significance of malignant cells present in pleural fluid is unknown due to low incidence of cytopathologic analysis in our cohort; therefore, the presence of an effusion does not appear to necessitate a change in therapy. Excellent survival can be expected with current stage-specific treatment regimens.

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.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.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, p0.001), smaller diameter on first prenatal ultrasound (15.8 vs. 39.7 mm, p0.001), change in sonographic character from simple to complex (87% vs 22%, p0.001), and postnatal sonographic characteristics of complex cyst (87% vs. 48%, p = 0.004).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.

Pleuropulmonary blastoma (PPB) is a rare pediatric cancer, and although there have been improvements in its treatment approach, recurrences retain a very poor prognosis. Here, we report a case of a 30-month-old female who survived recurrent PPB after undergoing surgery, adjuvant chemotherapy, intrapleural cisplatin infusion, and targeted therapy through whole exome sequencing (WES). Intrapleural cisplatin infusion and target therapy appear to be safe and can be considered in a multimodal approach for the management of recurrent PPB.

Risk factors for paediatric inguinal hernia are poorly understood. This longitudinal cohort study assessed whether children with a maternal history of inguinal hernia or connective tissue disorders have a higher risk of developing inguinal hernias before 13 years of age.The study included children followed up between birth and 13 years of age in Quebec, Canada, 2006-2019. Newborns whose mothers had inguinal hernias or connective tissue disorders were followed over time to identify future hospital admissions for inguinal hernia. Cox proportional hazards regression adjusted for patient characteristics was used to estimate hazard ratios (HRs) and 95 per cent confidence intervals for the association between maternal hernia or connective tissue disorders and future childhood hernias. Associations in girls and boys were examined separately.The study included 786 322 children with 6 186 448 person-years of follow-up. There were 6861 children with inguinal hernias, corresponding to an incidence of 11.1 per 10 000 person-years. Children with a maternal history of inguinal hernia had 2.92 (95 per cent c.i. 2.39 to 3.58) times the risk of having inguinal hernias relative to children whose mothers had no such history. Children with a maternal history of connective tissue disorders had 1.30 (1.00 to 1.68) times the risk. Maternal hernias were strongly associated with risk of inguinal hernias in girls (HR 5.34, 3.82 to 7.47), whereas maternal connective tissue disorders were associated with inguinal hernias in boys (HR 1.35, 1.02 to 1.79).Paediatric inguinal hernias may be associated with maternal inguinal hernias and connective tissue disorders, but the underlying reason for this relationship requires further investigation.In this study of 786 322 children in Canada from 2006 to 2019, it was found that children whose mothers had an inguinal hernia or connective tissue disorder were more at risk of developing a hernia themselves. Repairs for inguinal hernia are among the most common operations performed in children. The results showed that girls whose mothers had an inguinal hernia had more than five times the risk of developing an inguinal hernia before 13 years of age. Boys whose mothers had connective tissue disorders had a 35 per cent greater risk of inguinal hernia. These findings suggest that inguinal hernias may be inherited.

Pilocytic astrocytoma (PA) is emerging as a tumor entity with dysregulated RAS/RAF/MEK/ERK signaling. In this study, we report the identification of a novel recurrent BRAF insertion (p.V504_R506dup) in five PA cases harboring exclusively this somatic tandem duplication. This recurrent alteration leads to an addition of three amino acids in the kinase domain of BRAF and has functional impact on activating MAPK phosphorylation. Importantly, we show that this mutation confers resistance to RAF inhibitors without changing effectiveness while downstream MEK inhibitors remain effective. Our results further emphasize the importance of BRAF alterations in PA and the need to characterize them in a given tumor as this can affect therapeutic strategies and their potential use as tumor marker in molecular diagnostics.

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p

The etiology of pediatric abdominal disorders is poorly understood, and the relationship with maternal mental health is understudied. We sought to determine the association between maternal psychiatric disorders and abdominal conditions in childhood. We performed a retrospective cohort study of 1,080,518 newborns in Quebec, Canada, between 2006 and 2020. We identified maternal mental disorders before or during pregnancy and computed the incidence of abdominal disorders in offspring before 1 year of age. Outcomes included Hirschsprung disease; hypertrophic pyloric stenosis; and esophageal, intestinal, and biliary atresia. We calculated adjusted risk ratios (RR) with 95% confidence intervals (CI) for the association of maternal mental disorders with these pediatric abdominal disorders. Among 51,371 children exposed to maternal mental disorders, 200 children had an abdominal condition, for a rate of 38.9 cases per 10,000 children (95% CI 33.6–44.3) compared with 27.7 per 10,000 for children who were unexposed to maternal mental disorders (95% CI 26.7–28.7). Compared with no mental disorder, maternal mental disorders were associated with hypertrophic pyloric stenosis (RR 1.39, 95% CI 1.16–1.68). Associations were stronger for severe mental disorders and were more marked for depression and stress and anxiety disorders. Maternal mental disorders are associated with the risk of hypertrophic pyloric stenosis in offspring. The origin of hypertrophic pyloric stenosis may relate to maternal mental disorders that were present during pregnancy.

Background To better characterize short-term and long-term outcomes in children with pancreatic tumors treated with pancreaticoduodenectomy (PD). Methods Patients 21 years of age or younger who underwent PD at Pediatric Surgical Oncology Collaborative (PSORC) hospitals between 1990 and 2017 were identified. Demographic, clinical information, and outcomes (operative complications, long-term pancreatic function, recurrence, and survival) were collected. Results Sixty-five patients from 18 institutions with a median age of 13 years (4 months-22 years) and a median (IQR) follow-up of 2.8 (4.3) years were analyzed. Solid pseudopapillary tumor of the pancreas (SPN) was the most common histology. Postoperative complications included pancreatic leak in 14% (n = 9), delayed gastric emptying in 9% (n = 6), marginal ulcer in one patient, and perioperative (30-day) death due to hepatic failure in one patient. Pancreatic insufficiency was observed in 32% (n = 21) of patients, with 23%, 3%, and 6% with exocrine, or endocrine insufficiencies, or both, respectively. Children with SPN and benign neoplasms all survived. Overall, there were 14 (22%) recurrences and 11 deaths (17%). Univariate analysis revealed non-SPN malignant tumor diagnosis, preoperative vascular involvement, intraoperative transfusion requirement, pathologic vascular invasion, positive margins, and need for neoadjuvant chemotherapy as risk factors for recurrence and poor survival. Multivariate analysis only revealed pathologic vascular invasion as a risk factor for recurrence and poor survival. Conclusion This is the largest series of pediatric PD patients. PD is curative for SPN and benign neoplasms. Pancreatic insufficiency is the most common postoperative complication. Outcome is primarily associated with histology.

The aim of the study was to evaluate the outcomes of prophylactic thyroidectomies performed in an academic setting in the context of multiple endocrine neoplasia type 2 (MEN2) syndrome.A chart review of patients18years old who underwent prophylactic thyroidectomy for a MEN2 syndrome at a children's hospital between 2006 and 2015 was performed.The study included 21 patients (57% female) with a mean age of 6.2±2.5years. All patients were asymptomatic at first evaluation. Nineteen had MEN2A syndrome with RET proto-oncogene mutations identified. The remaining two were RET-negative with familial medullary thyroid cancer (FMTC). One patient had a concomitant Hirschsprung disease. Of the 11 patients who had RET proto-oncogene mutations ranked as Moderate Risk for medullary thyroid cancer (MTC) (American Thyroid Association), one had a microcarcinoma on the resected specimen, and the others had C-Cell Hyperplasia. Among the 8 patients who had RET proto-oncogene mutations ranked as High Risk level for MTC, all had microcarcinoma. Of the nine patients with microcarcinoma, three underwent surgery after 5years of age. No microcarcinoma exceeded 6mm. There were no permanent complications. Six patients experienced transient hypocalcemia, of which only one was symptomatic. No patients had lymph node involvement, and no recurrence was noted during the follow-up period.Of 21 children with familial thyroid cancer syndrome who underwent a prophylactic thyroidectomy, nine had microcarcinoma. This study highlights the need for a complete familial history, including FMTC history and mandatory preventive surgical approach.III.

Necrotizing enterocolitis (NEC) is exceptional after the neonatal period. A toddler with encephalopathy, mitochondrial myopathy, and hypertrophic cardiomyopathy developed fatal NEC and multiple organ dysfunction within 48 hours of the introduction of enteral feeding. She was subsequently found to have pathogenic mutations in FBXL4, a cause of mitochondrial DNA depletion syndrome-13. Intestinal dysmotility in the context of deficient mitochondrial respiration may have contributed to the development of NEC. Current paradigms call for early introduction of enteral nutrition to reinstate energy homeostasis. Enteral feeding should be administered with caution during metabolic crises of patients with mitochondrial DNA depletion syndromes.

Importance Little progress in pediatric cancer treatment has been noted in the past decade, urging the development of novel therapeutic strategies for adolescents and children with hard-to-treat cancers. Use of comprehensive molecular profiling in the clinical management of children and adolescents with cancer appears a suitable approach to improve patient care and outcomes, particularly for hard-to-treat cases. Objective To assess the feasibility of identifying potentially actionable mutations using next-generation sequencing–based assays in a clinically relevant time frame. Design, Setting, and Participants This diagnostic study reports the results of the TRICEPS study, a prospective genome sequencing study conducted in Quebec, Canada. Participants, aged 18 years or younger at diagnosis, with refractory or relapsed childhood and adolescent cancers were enrolled from April 2014 through January 2018. Whole-exome sequencing (WES) of matched tumor normal samples and RNA sequencing of tumor were performed to identify single-nucleotide variants, fusion transcripts, differential gene expression, and copy number alterations. Results reviewed by a team of experts were further annotated, synthesized into a report, and subsequently discussed in a multidisciplinary molecular tumor board. Main Outcomes and Measures Molecular profiling of pediatric patients with hard-to-treat cancer, identification of actionable and targetable alteration needed for the management of these patients, and proposition of targeted and personalized novel therapeutic strategies. Results A total of 84 patients with hard-to-treat cancers were included in the analysis. These patients had a mean (range) age of 10.1 (1-21) years and a similar proportion of male (45 [54%]) and female (39 [46%]). Sixty-two patients (74%) had suitable tissues for multimodal molecular profiling (WES and RNA sequencing). The process from DNA or RNA isolation to genomic sequencing and data analysis steps took a median (range) of 24 (4-41) days. Potentially actionable alterations were identified in 54 of 62 patients (87%). Actions were taken in 22 of 54 patients (41%), and 18 (33%) either were on a second or third line of treatment, were in remission, or had stable disease and thus no actions were taken. Conclusions and Relevance Incorporating genomic sequencing into the management of hard-to-treat childhood and adolescent cancers appeared feasible; molecular profiling may enable the identification of potentially actionable alterations with clinical implications for most patients, including targeted therapy and clinically relevant information of diagnostic, prognostic, and monitoring significance.

10024 Background: Inflammatory myofibroblastic tumor (IMT) is a mesenchymal neoplasm of intermediate malignancy, predominantly seen in children and young adults. Given its rarity, data are limited. We describe the largest cohort of patients with IMT to date, with an aim to further characterize this poorly understood tumor. Methods: A multi-institutional review was performed at 18 North American hospitals participating in the Pediatric Surgical Oncology Research Collaborative to identify IMT patients ≤39 years, diagnosed from 2000-2018. Descriptive statistics are described as median and interquartile range. Multivariable analysis was used to identify predictors of event free survival (EFS). Results: 182 patients were identified with a median age of 11 years (5-17); 52% were female. 33% of tumors were thoracic, 26% abdominal/pelvic, 20% head/neck, and 14% genitourinary. Common presenting symptoms included pain (29%), respiratory symptoms (24%), weight loss (12%), and a palpable mass (10%). Median tumor size was 3.9 cm (1.9-6.5). Anaplastic lymphoma kinase (ALK) overexpression was identified via immunohistochemistry in 53% of patients tested. One third of patients had abnormal cytogenetics, with 12% of the entire cohort having an ALK mutation. 7% of patients had distant disease at diagnosis. 13% of patients received neoadjuvant therapy including chemotherapy (3%), ALK inhibitor (4%), radiation (0.5%), non-steroidal anti-inflammatories (NSAIDs) (7%), or steroids (2%). Of those who underwent resection with known margin status (n = 158), 66% had complete resection, 20% had microscopic positive margins, and 14% had gross residual disease. Just over 40% of patients had an en bloc resection of involved organs, most commonly lung (26%). 21% of patients received adjuvant therapy, including chemotherapy (3%), ALK inhibitor (9%), radiation (0.5%), NSAIDs (8%), or steroids (5%). 12% of all patients received an ALK inhibitor: 24% neoadjuvant, 62% adjuvant, and 14% without surgery. Median follow-up time was 36 months (14-69). Overall 5-year survival (OS) was 95% and 5-year EFS was 80%. Predictors of recurrence included respiratory symptoms, larger tumor size, or distant disease at diagnosis. Gender, race, age and primary site were not predictive of EFS. Likewise, there was no association of ALK overexpression or ALK mutation with EFS. The presence of gross or microscopic margins following resection was not associated with recurrence. Conclusions: IMT is a rare tumor with favorable OS. Five year recurrence rate was 20%. Presenting with respiratory symptoms, larger tumor size, or metastatic disease was associated with recurrence, while ALK positivity was not. Notably, a positive margin after resection was not associated with increased recurrence, indicating that aggressive attempts at surgical resection that would compromise form or function may not be warranted.

BACKGROUND: Optimal management of neutropenic appendicitis (NA) in children undergoing cancer therapy remains undefined. Management strategies include upfront appendectomy or initial nonoperative management. We aimed to characterize the effect of management strategy on complications and length of stay (LOS) and describe implications for chemotherapy delay or alteration. METHODS: Sites from the Pediatric Surgery Oncology Research Collaborative performed a retrospective review of children with NA over a 6-year period. RESULTS: Sixty-six children, with a median age of 11 years (range 1–17), were identified with NA while undergoing cancer treatment. The most common cancer diagnoses were leukemia (62%) and brain tumor (12%). Upfront appendectomy was performed in 41% of patients; the remainder had initial nonoperative management. Rates of abscess or perforation at diagnosis were equivalent in the groups (30% vs 24%; P = .23). Of patients who had initial nonoperative management, 46% (17 of 37) underwent delayed appendectomy during the same hospitalization. Delayed appendectomy was due to failure of initial nonoperative management in 65% (n = 11) and count recovery in 35% (n = 6). Cancer therapy was delayed in 35% (n = 23). Initial nonoperative management was associated with a delay in cancer treatment (46% vs. 22%, P = .05) and longer LOS (29 vs 12 days; P = .01). Patients who had initial nonoperative management and delayed appendectomy had a higher rate of postoperative complications (P CONCLUSIONS: In pediatric patients with NA from oncologic treatment, upfront appendectomy resulted in lower complication rates, reduced LOS, and fewer alterations in chemotherapy regimens compared to initial nonoperative management.

Aim of the study Recent publications suggest pediatric surgeons may not be well suited to perform thyroid surgeries unless considered high volume. We sought to assess the outcome of thyroidectomies performed by pediatric surgeons in an academic setting. Methods We reviewed charts of patients younger than 18 years who underwent thyroid surgeries at a free standing children's hospital between April 2006 and October 2015. Main results The analysis included 118 surgeries in 98 patients (mean age 11.8 years). Most surgeries were performed by a single pediatric surgeon (average 10 thyroidectomies per year). The commonest indication for resection was thyroid nodule (64%). 80% of patients had a single surgery; the remainder had two, including 13 completion hemithyroidectomies. Cancer was found in 37% of specimens, with papillary subtype being most common (72%). Seven patients had locoregional metastases and one had pulmonary metastases. Among the 17 malignant cases that had a second intervention, 6 had malignancy in the resected specimen. There were no deaths in the follow up period (mean 2.7 years). Two patients had permanent hypocalcemia, and three had persistent unilateral recurrent laryngeal nerve injuries causing dysphonia for a total permanent complication rate of 4.2%. Conclusions We conclude that pediatric thyroidectomy is a safe procedure when performed by pediatric surgeons. Our rate of complications is comparable to those reported in the literature. Our data highlight the need for a vigilant and multidisciplinary approach for children with thyroid pathology. Type of study Treatment study. Level of evidence IV.

Introduction Pediatric surgeons are often involved in the management of severely or terminally ill patients. However, articles addressing their specific roles in the context of palliative care are almost inexistent. We sought to characterize the involvement of pediatric surgeons caring for children near end of life. Methods Chart review of children who had a procedure under general anesthesia within 6months of their death over a five-year period at a tertiary children's hospital (excluding traumas and neonatology cases). In addition to demographic and clinical data, we recorded the aim of the procedures performed, the involvement of the palliative care service, and presence of DNAR orders. Results The analysis included 83 patients (mean age: 8years). Forty-four children had more than one procedure (range 2–10). Pediatric palliative care service was involved in 66 cases (80%). A majority of patients had cancer (50%), and the most frequent cause of death was oncologic progression (46%). Ten patients died of a complication following their intervention. The aim of the procedure was palliative in 48 cases (29 for symptoms control and 19 to facilitate care), diagnostic in 16, and curative in 19. Forty-five procedures were performed urgently and 14 despite DNAR orders. Conclusion Surgeon involvement with children near end of life is not infrequent. The procedures performed are varied and can be categorized according to their aim. Lack of formal palliative care training by surgeons highlights the need for increased collaboration with palliative care services to provide children optimal care when they need it most. Level of Evidence IV.

Background Despite randomized controlled trials and meta-analyses, it remains unclear whether laparoscopic pyloromyotomy (LP) carries a higher risk of incomplete pyloromyotomy and mucosal perforation compared with open pyloromyotomy (OP). Methods Multicenter study of all pyloromyotomies (May 2007–December 2010) at nine high-volume institutions. The effect of laparoscopy on the procedure-related complications of incomplete pyloromyotomy and mucosal perforation was determined using binomial logistic regression adjusting for differences among centers. Results Data relating to 2830 pyloromyotomies (1802 [64%] LP) were analyzed. There were 24 cases of incomplete pyloromyotomy; 3 in the open group (0.29%) and 21 in the laparoscopic group (1.16%). There were 18 cases of mucosal perforation; 3 in the open group (0.29%) and 15 in the laparoscopic group (0.83%). The regression model demonstrated that LP was a marginally significant predictor of incomplete pyloromyotomy (adjusted difference 0.87% [95% CI 0.006–4.083]; P =0.046) but not of mucosal perforation (adjusted difference 0.56% [95% CI −0.096 to 3.365]; P =0.153). Trainees performed a similar proportion of each procedure (laparoscopic 82.6% vs. open 80.3%; P =0.2) and grade of primary operator did not affect the rate of either complication. Conclusions This is one of the largest series of pyloromyotomy ever reported. Although laparoscopy is associated with a statistically significant increase in the risk of incomplete pyloromyotomy, the effect size is small and of questionable clinical relevance. Both OP and LP are associated with low rates of mucosal perforation and incomplete pyloromyotomy in specialist centers, whether trainee or consultant surgeons perform the procedure.

OBJECTIVES: All-terrain vehicle (ATV) legislation in Quebec is among the most restrictive in Canada. The purpose of our study was to characterize the pediatric ATV traumas in our center and determine the impact of legislation. METHODS: Retrospective chart review of all patients seen in the emergency department after an ATV injury was done from 2005 to 2011. RESULTS: Seventy-tree patients (50 boys and 23 girls) with a mean age of 11 years (range, 3-17 years) were identified. Forty-nine percent were drivers, 40% were passengers, and 11% unknown. Forty-five percent did not reach the legal age of 16 years. Helmet use was documented in 36%. Eighty-five percent were admitted to the floor, and 15% were discharged from the emergency department. Intensive care unit stay was necessary in 21%, and 60% were operated on. Most of the surgeries were for orthopedic, either extremities, spine, or pelvic (80%). The most frequent types of trauma were extremities (30%), head (30%), and face (25%). Head trauma was severe in 23%. Hospitalization rates for ATV injuries have remained unchanged in the last years. CONCLUSIONS: Despite implementation of ATV legislation regarding helmet use and minimal legal age, a lot of our patients did not obey these rules. This study demonstrates that strong legislation did not have a real impact on ATV morbidity in children. It is essential to develop strategies to enforce ATV users to respect legislation. Language: en

Perianal rhabdomyosarcoma is a rare type of tumor with a relatively poor prognosis. We present the case of a patient who presented with a cutaneous perianal hamartoma at the age of 6 weeks. 21 months latter a recurrent mass at the excision site proved to be an embryonal rhabdomyosarcoma involving the anal sphincter. A pathologic review of the two specimens confirmed their relatedness. This report highlights the need to maintain a high level of suspicion in cases of recurrence following excision of a benign lesion.

Childhood cancer is a group of heterogeneous complex diseases. Although 80% of these children are cured with conventional therapies, it remains the first cause of death among children in Western countries. A significant number of refractory/relapse patients will eventually succumb to their disease and the lack of therapeutic advances for these patients is even more worrisome. Indeed, no significant progress has been noted over the last decade for these patients, urging the need for new and more effective therapeutic approaches. Precision medicine and more effective personalized targeted therapies (PTT) are a major breakthrough leading to increased cure rates and decreased treatment-related morbidity and mortality for the patients with refractory or relapsed tumors. To address this challenge, the TRICEPS study was initiated on April 2014 at the Sainte-Justine UHC (Montreal, Canada) with an overreaching goal to explore the feasibility of performing genomic-driven targeted therapy in pediatric and adolescent (aged 0-21 years) patients with relapsed or refractory childhood cancer. This study offers in-depth genomic and transcriptomic investigation of patient’s tumoral material to identify patient-specific alterations and actionable driver mutation(s) that can be targeted with approved targeted drug and within a reasonable clinically relevant timeframe to assess the feasibility of going from biopsy to a detailed tumor analysis report. Over a period of 30 months, 44 relapsed/refractory cancer patients were recruited. Twenty-two of them underwent extensive genomic investigation (exomic and transcriptomic sequencing) within a median timeframe of 9.7 weeks from patient enrolment to return of results. Patient screen failures occurred due to benign/necrotic tumor biopsies or low tumor purity resulting in suboptimal DNA/RNA quantity or quality for genomic analysis. In all 22 patients, we have identified clinically relevant genomic alterations (SNVs, indels, fusions, CNAs) and relapse-specific mutations influencing patient management and providing options for personalized interventions. We assessed the functional impact of some of these cancer-specific alterations. This was the case of a novel relapse-specific rearrangement, identified on relapsed childhood ETP-ALL, and leading to asparagine synthetase (ASNS) up-regulation through a promoter exchange. The expression of this fusion was associated with reduced apoptosis following l-asparaginase treatment. This study shows that PPT based on next generation sequencing technology is a powerful approach that could be implemented in the clinic within a foreseeable future to guide treatment of hard-to-treat childhood cancers and to further improve patient care and outcomes. Citation Format: Fida Khater, Stephanie Vairy, Sylvie Langlois, Jasmine Healy, Sophie Dumoucel, Mathieu Lajoie, Thomas Sontag, Pascal St-Onge, Henrique Bittencourt, Dorothée Dal Soglio, Anne-Sophie Carret, Sonia Cellot, Josette Champagne, Michel Duval, Maja Krajinovic, Jean-Marie Leclerc, Valerie Larouche, Natalie Patey, Sébastien Perreault, Nelson Piché, Yvan Samson, Pierre Teira, Monia Marzouki, Daniel Sinnett. Identification of actionable targets for refractory/relapsed childhood cancer leading to personalized targeted therapy (TRICEPS Study) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4885. doi:10.1158/1538-7445.AM2017-4885

In Canada, about 1500 pediatric cancers are diagnosed each year. Despite improvements in risk-stratified treatments, around 20% of childhood cancer patients do not respond to current therapies and ultimately succumb to their disease, urging the need for new and more effective therapeutic approaches. Personalized targeted therapy (PTT) based on next generation sequencing (NGS) may be a key component to increase cure rates and decrease treatment-related morbidity and mortality. To assess the feasibility of performing PTT clinical trials in the context of childhood cancers, a pilot study is currently underway at the Sainte-Justine UHC, Montreal, where 30 relapsed or refractory cancer patients (aged 0-21 years) are being recruited over a 2 year period and offered in-depth genomic and transcriptomic investigation to identify patient-specific alterations. This pilot study will allow us to determine the number of children with cancer who are suitable candidates for targeted therapy, to determine the number and type of driver mutation(s) found in the recurrent or refractory childhood cancers, to determine the number of cancer patients who harbor actionable driver mutation(s) that can be targeted with a Health Canada/FDA approved targeted drug and to assess the feasibility of going from biopsy to a detailed tumour analysis report within a clinically-relevant timeframe. Thus far, sixteen patients have been recruited in this study between April 2014 and July 2015. Study subject accrual has been successful with 100% compliance. Eight patients have undergone extensive genomic investigation in a real-time manner. We identified clinically relevant genomic alterations (singe nucleotide variants or structural variations) that can be used to inform clinical management for 8/8 of these patients. Patient screen failures occurred due to benign tumor biopsies, necrotic tumor tissue or low tumor purity, resulting in suboptimal DNA/RNA quantity or quality for NGS. Identified relapse-specific mutations allowed follow up of minimal residual disease, particularly post-transplant for relapsed leukemia cases, influenced patient management and revealed alternative therapeutic options for future personalized targeted therapy. This feasibility study shows that PTT based on NGS technology is a useful approach that could be implemented in the clinic within a foreseeable future to guide treatment of relapsed or refractory childhood cancer patients. The following step toward translating our results into novel personalized therapeutic approaches will be the development of phase II clinical trials to evaluate the efficacy of these targeted therapies in terms of therapeutic response, survival, and overall quality of life. Our overreaching goal is to be able to offer personalized targeted therapy options to all patients upon primary diagnosis of their cancer. Citation Format: Sylvie Langlois, Jasmine Healy, Mathieu Lajoie, Sophie Dumoucel, Fida Khater, Thomas Sontag, Pascal St-Onge, Patrick Beaulieu, Henrique Bittencourt, Dorothée Dal Soglio, Anne-Sophie Carret, Sonia Cellot, Josette Champagne, Michel Duval, Maja Krajinovic, Jean-Marie Leclerc, Natalie Patey, Nelson Piché, Yvan Samson, Pierre Teira, Monia Marzouki, Daniel Sinnett. TRICEPS: A feasibility study of personalized targeted therapy in relapsed/refractory childhood cancers. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Pediatric Cancer Research: From Mechanisms and Models to Treatment and Survivorship; 2015 Nov 9-12; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(5 Suppl):Abstract nr A41.

Minimally invasive surgery (MIS) for nephrectomy has been described since the early 1990s. More recently, MIS has been used for nephron-sparing surgery (NSS) when treating benign conditions. However, reports of NSS using MIS for malignant conditions are sparse. In this report, we describe our retroperitoneal laparoscopic approach for NSS for a localized Wilms tumor.

Objective To study the effect of heat on the absorption of intraperitoneal (IP) oxaliplatin using a murine model. Background Because of its efficiency in the systemic treatment of colorectal cancer, oxaliplatin is currently used in hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis. However, its properties when administered by the IP route have not been well characterized by preclinical studies. Methods Under general anesthesia, 35 Sprague-Dawley rats were submitted to 3 different doses of IP oxaliplatin (460, 920, and 1840 mg/m(2)) at 3 different perfusion temperatures (37, 40, and 43°C) during 25 minutes. At the end of perfusion, samples in different compartments (peritoneum, portal blood, and systemic blood) were harvested and the concentrations of oxaliplatin were measured by high performance liquid chromatography. Results As the dose of IP oxaliplatin was increased, higher concentrations were observed in every compartment. When the temperature of IP oxaliplatin was increased, it resulted in an increase of its peritoneal concentration (linear regression 0.38; 95% CI: 0.28-0.47) and in a decrease of its systemic blood (linear regression -1, 02; 95% CI: -1.45 to -0.60) and portal blood (linear regression -1.08; 95% CI: -1.70 to -0.47) concentrations. Conclusion Proportionally to the dose administered, IP oxaliplatin leads to high concentration of drug in peritoneal tissues. Furthermore, heat enhances peritoneal tissue concentration of Oxaliplatin while reducing its systemic absorption. This last effect may possibly lead to decreased systemic toxicity. These observations support the use of oxaliplatin for HIPEC.

Despite all recent advances in cancer's treatment, 18% of children will die from their cancer. New tools that enable better individual tumor characterization and classification are required to improve patient care and outcomes on children. Personalized targeted therapy has proven to be a promising strategy for first line treatment in adult cancer. Given the high heterogeneity in childhood cancers, access to histopathology-based clinical trials for targeted therapy is challenging and facilitated by the capacity to sequence individual childhood tumors in real time. A feasibility study is currently underway at the CHU Sainte-Justine, Montreal, where 30 relapse or refractory cancer patients between 0 and 21 years, are being offered in-depth genomic and transcriptomic investigation to identify patient-specific alterations that may be targetable with alternative therapies. This pilot study will allow us to address the following questions: 1) determine the number of children with cancer who are suitable candidates for targeted therapy at our institution each year, 2) determine the number and type of driver mutation(s) found in our population of recurrent or refractory cancers, 3) determine the number of cancer patients who harbour actionable driver mutation(s) that can be targeted with a Health Canada approved targeted drug, 4) assess the feasibility of obtaining high quality/quantity biospecimen, performing genomic sequencing and data analysis, identifying a drug based on the genomic data and offering this information to the medical team, the patient and the family within a 10-week time frame. The following step toward translating our results into novel personalized therapeutic approaches will then be the development of phase II clinical trials to evaluate the efficacy of these targeted therapies in terms of therapeutic response, survival, and overall quality of life. Our overreaching goal is to be able to offer personalized targeted therapy options to all patients upon primary diagnosis of their cancer.

14535 Background: Whereas in vitro studies have demonstrated that hyperthermia enhances the cytotoxicity and tissue penetration of oxaliplatin, in vivo studies conducted so far have failed to document clearly such effect in the context of heated intraperitoneal chemotherapy. The purpose of this study is to assess the effect of heat on the pharmacokinetic profile of oxaliplatin administered intraperitonealy in rats. Methods: Under general anesthesia, 25 Sprague-Dawly rats of 258 g (235–440 g) were submitted to 3 different doses of intraperitoneal oxaliplatin (460, 920 and 1840 mg/m2) at 3 different temperatures of perfusion (37, 40 and 43°C) during 25 minutes. At the end of perfusion, samples in different compartments were harvested for dosage of oxaliplatin concentration: 2 ml of perfusate, 1 ml of portal blood, 1 ml of systemic blood, 100 mm3 of parietal peritoneum and 100 mm3 of mesentery. Dosage of oxaliplatin was performed by high performance liquid chromatography. Results: We observed a linear and proportional correlation between the concentration of oxaliplatin in the perfusate and the concentration of oxaliplatin for all compartments (R2 : 0.9833 for systemic blood, 0.9874 for portal blood, 0.9053 for parietal peritoneum and 0.9999 for mesentery). Regarding the effect of temperature, we observed a linear and proportional correlation of heat on the concentration of oxaliplatin in parietal peritoneum (R2 : 0.8543), no effect on mesentery (R2: 0.1371) and a tendency of heat to limit concentration of oxaliplatin in portal and systemic blood (R2 = 0.0994 and 0.5854 respectively). Conclusion: Heat improves the absorption of oxaliplatin into the peritoneal cells and seems to limit the systemic absorption of oxaliplatin, the latter observation suggesting a decrease in systemic toxicity. These are two strong arguments supporting the use of oxaliplatin by intraperitoneal route, as it is currently done in the human treatment of peritoneal carcinomatosis from colorectal origin. No significant financial relationships to disclose.