Do Children With Osteosarcoma Benefit From Pulmonary Metastasectomy?: A Systematic Review of Published Studies and "Real World" Outcomes.

OBJECTIVE: To critically examine the evidence-base for survival benefit of pulmonary metastasectomy (PM) for osteosarcoma (OS) in the pediatric population. BACKGROUND: PM for OS is recommended as the standard of care in both pediatric and adult treatment protocols. Recent results from the "Pulmonary Metastasectomy in Colorectal Cancer" trial demonstrate no survival benefit from PM in colorectal cancer in adults. METHODS: A systematic review was undertaken according to "Preferred Reporting Items for Systematic Reviews and Meta-Analysis" guidelines. Medline, Embase, and 2 clinical trial registers were searched for all studies detailing pediatric patients with OS (<18 years) undergoing PM with a comparison cohort group that did not receive PM. RESULTS: Eleven studies met inclusion criteria dating from 1984 to 2017. All studies were retrospective and none directly compared PM versus no PM in pediatric patients as its main objective(s). Three-year survival rates ranged from 0% to 54% for PM and 0% to 16% for no PM. No patients receiving PM were usually those with unresectable disease and/or considered to have a poor prognosis. All studies were at high risk of bias and there was marked heterogeneity in the patient selection. CONCLUSIONS: There is a weak evidence base (level IV) for a survival benefit of PM for OS in pediatric patients likely due to selection bias of "favorable cases." The included studies many of which detailed outdated treatment protocols were not designed in their reporting to specifically address the questions directly. A randomized controlled trial-while ethically challenging in a pediatric population-incorporating modern OS chemotherapy protocols is needed to crucially address any "survival benefit."

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

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

Utility of the oxygenation index in management of congenital diaphragmatic hernia: a report from a Thai University Surgical Centre.

BACKGROUND: Oxygenation index (OI) is associated with severity of newborn pulmonary hypertension (PH) in congenital diaphragmatic hernia (CDH). Higher OI may indicate worst degree(s) of PH. OBJECTIVES: This study reports OI dynamic(s) over the first 72 h of life and its correlation with (1) perioperative morbidity and (2) CDH mortality. METHODS: Medical records of inborn CDH babies during 2002-2022 were examined. OI on Days (s) 1-3 and perioperative OI trends were recorded. Operation (primary vs patch repair) and survival rates (%) were studied. RESULTS: Fifty-five CDH newborns (54.5% male: 45.5% female)-mean birth GA 37.5 ± 2.7 wks. had a mean birth weight 2813 ± 684 g with prenatal diagnosis in 32.7% cases. 52/55 (94.5%) were intubated at birth and HFOV deployed in 29 (55.8%). Those requiring HFOV had higher OI on DOL1 (24.8 ± 17 vs 10.3 ± 11.5; p < 0.05), DOL 2 (26.3 ± 22.9 vs 6.7 ± 12.1; p < 0.05) and DOL 3 (21.9 ± 33.8 vs 5.5 ± 9.3; p = 0.04). Operation was undertaken in 36/55 (65.5%). Preoperative mortality group had significant higher OI on DOL 2 (42.1 ± 21.0 vs 14.9 ± 9.3; p = 0.04). CDH defects were-Type A N = 27 (75%), Type B N = 7 (19.4%) and Type C N = 2 (5.6%). Overall mortality was 40% (22/55). Statistically significant OI trends were recorded in non-survival vs. survival groups on DOL 1 (31.6 ± 16.8. vs 10.5 ± 9.0; p < 0.05, DOL 2 (38.1 ± 21.9 vs 6.3 ± 7.1; p < 0.05), and DOL 3 (38.8 ± 39.4; p = 0.012). CONCLUSIONS: OI dynamics are highly predictive for accurate monitoring of CDH cardiorespiratory physiology and crucially may guide ventilatory management as well as timing of surgery.

Sacrococcygeal teratoma: Long-term outcomes. A UK CCLG Surgeons Group Nationwide Study.

AIM: Sacrococcygeal teratoma (SCT) is a rare paediatric germ cell tumour (1:40,000). Long-term data regarding urinary tract and bowel function after SCT resection is limited to few studies. A UK Children's Cancer and Leukaemia Group (CCLG) Surgeons multicentre study aimed to critically analyse long-term functional outcomes in patients following resection of SCT. METHODS: Nationwide study of UK paediatric surgical oncology centres using a standardised data collection form. All index cases of newborn infants and children <16 years with SCT diagnosis during 2005-2015 were included. RESULTS: 165 SCT patients treated at 14 UK paediatric surgical oncology centres were included. Median age at presentation was 1 day [interquartile range, IQR: 0-25]; median age at surgery was 10 days [IQR: 4-150]. One hundred seventeen (70%) were female and 48 (30%) male. Antenatal diagnosis was made in 44% index cases. Total 59% of patients were Altman Stage I or II lesions. Follow-up data were available in 83% cases. Tumour recurrence occurred in 13 (7%) patients at median age 13 months [IQR: 8.75-30 months]. Fifty-nine (36%) of 165 patients had documented adverse bladder or bowel dysfunction. Twenty-two (37%) cases required urinary clean intermittent catheterisation (CIC) urology health care, with eight patients (14%) needing operative intervention to control management of bowel dysfunction. CONCLUSION: This UK CCLG study showed 36% of SCT patients develop bladder or bowel dysfunction after primary tumour resection. Functional assessment of bladder and bowel function is mandatory during after-care follow-up of all SCT patients. A multidisciplinary care pathway, with surgeon speciality groups including surgical oncology, paediatric urology and paediatric colorectal specialists, is strongly advised to facilitate 'best practice' monitoring of long-term health and improve patient quality of life (QoL) into adulthood.

A Novel Standard for Systematic Reporting of Neuroblastoma Surgery: The International Neuroblastoma Surgical Report Form (INSRF): A Joint Initiative by the Pediatric Oncological Cooperative Groups SIOPEN∗, COG∗∗, and GPOH∗∗∗.

OBJECTIVE: To create the first structured surgical report form for NBL with international consensus, to permit standardized documentation of all NBL-related surgical procedures and their outcomes. SUMMARY OF BACKGROUND DATA: NBL, the most common extracranial solid malignant tumor in children, covers a wide spectrum of tumors with significant differences in anatomical localization, organ or vessel involvement, and tumor biology. Complete surgical resection of the primary tumor is an important part of NBL treatment, but maybe hazardous, prone to complications and its role in high-risk disease remains debated. Various surgical guidelines exist within the protocols of the different cooperative groups, although there is no standardized operative report form to document the surgical treatment of NBL. METHODS: After analyzing the treatment protocols of the SIOP Europe International Neuroblastoma Study Group, Children's Oncology Group, and Gesellschaft fuer Paediatrische Onkologie und Haematologie - German Association of Pediatric Oncology and Haematology pediatric cooperative groups, important variables were defined to completely describe surgical biopsy and resection of NBL and their outcomes. All variables were discussed within the Surgical Committees of SIOP Europe International Neuroblastoma Study Group, Children's Oncology Group, and Gesellschaft fuer Paediatrische Onkologie und Haematologie - German Association of Pediatric Oncology and Haematology. Thereafter, joint meetings were organized to obtain intercontinental consensus. RESULTS: The "International Neuroblastoma Surgical Report Form" provides a structured reporting tool for all NBL surgery, in every anatomical region, documenting all Image Defined Risk Factors and structures involved, with obligatory reporting of intraoperative and 30 day-postoperative complications. CONCLUSION: The International Neuroblastoma Surgical Report Form is the first universal form for the structured and uniform reporting of NBL-related surgical procedures and their outcomes, aiming to facilitate the postoperative communication, treatment planning and analysis of surgical treatment of NBL.

Standardizing the surgical management of benign ovarian tumors in children and adolescents: A best practice Delphi consensus statement.

AIM: No widely agreed consensus protocols exist for the management of benign ovarian tumors (BOT) in children. This presents a substantial risk for suboptimal management. We aimed to generate multispecialty consensus guidance to standardize surgical management and provide a clear follow-up protocol for children with BOTs. METHODS: Prospective two-round confidential e-Delphi consensus survey distributed among multispecialty expert panel; concluded by two semistructured videoconferences. MAIN RESULTS: Consensus was generated on these core outcome sets: preoperative/intraoperative management; follow-up; adolescent gynecology referral. (1) Children with BOTs should receive the same management as other patients with potentially neoplastic lesions: Preoperative discussion at a pediatric oncology multidisciplinary meeting to risk stratify tumors, and management by health professionals with expertise in ovarian-sparing surgery and laparoscopy. (2) Ovarian-sparing surgery for BOTs should be performed wherever possible to maximize fertility preservation. (3) Ovarian masses detected during emergency laparoscopy/laparotomy should be left in situ wherever feasible and investigated appropriately (imaging/tumor markers) before resection. (4) Follow-up should be undertaken for all patients after BOT resection. Patients should be offered referral to adolescent gynecology to discuss fertility implications. CONCLUSION: This best practice Delphi consensus statement emphasizes the importance of managing children with BOTs through a well-defined oncological MDT strategy, in order to optimize risk stratification and allow fertility preservation by ovarian-sparing surgery wherever possible.

Is Roux-en-Y Feeding Jejunostomy a Safe and Effective Operation in Children? A Systematic Review Exploring Outcomes.

OBJECTIVES: Roux-en-Y jejunostomy (REYJ) may establish feeding in children with foregut dysmotility or severe gastro-esophageal reflux disease (GERD). Nevertheless, concerns have been raised about safety and efficacy. We, therefore, evaluated outcomes of REYJ by systematic review to determine if this was a satisfactory option for achieving enteral autonomy in children with complex nutritional needs. METHODS: A PRISMA-adherent systematic review was conducted of studies reporting children undergoing feeding REYJ. Two authors performed processes independently; the senior author resolved disagreements. Embase, CINAHL and Medline were searched (inception-01/21). Additional databases, references, and 'grey' literature were searched. Methodological Index for Non-randomized Studies (MINORS) and a bespoke system assessed methodological quality. RESULTS: Of 362 articles, 10 met eligibility criteria (9 retrospective series; 1 conference proceeding). Unpublished data were also attained. Interobserver agreement for MINORS (kappa = 0.47) and bespoke scoring (kappa = 0.58) were moderate. After consensus, median MINORS score was 37.5% (IQR 6.3%) and bespoke 50% (IQR 20.8%), indicating poor methodological quality. One hundred sixty-four patients were reported (age range: 2 months to 19 years). Time to full feeds and length of stay were inadequately reported but most achieved enteral autonomy. No studies reported patient/caregiver-questionnaires. Seventy-six complications were documented (Clavien-Dindo grading was infeasible). Morbidity included peristomal leakage (N = 26), internal hernia/volvulus (N = 8), and SSI (N = 7). Thirty-eight patients died (2 procedure-attributable) during follow-up (range: 1 month to 15 years). CONCLUSIONS: Up to 50% patients experience complications after REYJ (often minor) with 23% patients dying during follow-up, often comorbidity-attributable. REYJ can achieve enteral autonomy although parents/caregivers of children should be counselled accordingly.

Postoperative feeding in neonatal duodenal obstruction.

BACKGROUND: Findings from manometry studies and contrast imaging reveal functioning gastric physiology in newborns with duodenal atresia and stenosis. Stomach reservoir function should therefore be valuable in aiding the postoperative phase of gastric feeding. The aim of this study was therefore to compare the feasibility of initiating oral or large volume(s) gavage feeds vs small volume bolus feeds following operation for congenital duodenal anomalies. METHODS: Single-center electronic medical records of all babies with duodenal atresia and stenosis admitted to a university surgical center during January 1997-September 2021 were analyzed. A fast-fed group (FF) included newborns fed with oral or gavage feeds advanced at a rate of at least 2.5 ml/kg and then progressed more than once a day vs slow-fed group (SF) fed with gavage feeds at incremental rate less than 2.5 ml/kg/day for each time period of oral tolerance or by drip feeds. Total feed volume was limited to 120-150 ml/kg/day in the respective study cohort populations. RESULTS: Fifty-one eligible patients were recruited in the study - twenty-six in FF group and twenty-five in SF group. Statistically significant differences were observed in the (i) date of first oral feeds (POD 7.7 ± 3.2 vs 16.1 ± 7.7: p < 0.001), and (ii) first full feeds (POD 12.5 ± 5.3 vs 18.8 ± 9.7: p < 0.01) in FF vs SF study groups. CONCLUSION: Initial feeding schedules with oral or incremental gavage-fed rates of at least 2.5 ml/kg in stepwise increments and multi-steps per day is wholly feasible in the postoperative feeding regimens of neonates with congenital duodenal disorders. Significant health benefits are thus achievable in these infants allowing an earlier time to acquiring full enteral feeding and their hospital discharge.

Clinical trials and outcome reporting in congenital diaphragmatic hernia overlook long-term health and functional outcomes-A plea for core outcomes.

AIM: To review the selection, measurement and reporting of outcomes in studies of interventions in Congenital Diaphragmatic Hernia (CDH). METHODS: We searched the Cochrane Central Register of Controlled Trials from 2000-2020 for randomised trials and observational studies. Outcomes reported were classified into seven key domains modelled on the patient journey. RESULTS: Our search yielded 118 papers; 27 were eligible. The most frequent domains measured were 'short-term markers of disease activity' (17/27), whereas long-term outcomes (3/27) and outcomes relating to functional health status (8/27) were reported infrequently. There was heterogeneity in the methods and timing of outcome reporting. Primary outcomes were varied and not always clearly stated. CONCLUSION: Long-term health and functional outcomes involving interventional studies in CDH are infrequently reported, which hinders the process of shared decision-making and evidence-based healthcare. A CDH core outcome set is needed to standardise outcome reporting that is relevant to both families and healthcare teams.

Congenital diaphragmatic hernia-does the presence of a hernia sac improve outcome? A systematic review of published studies.

Early reports have suggested survival benefits associated with a hernia sac in congenital diaphragmatic hernia (CDH). However, these studies have included only small subsets of patients. This systematic review aimed to evaluate differences in outcomes of CDH newborns with and without a hernia sac. PubMed and Embase databases were searched using relevant key terms. Papers were independently reviewed by two authors with final selection approved by the senior author. Original search retrieved 537 papers; the final review included 8 studies (n = 837 patients). There were 168 CDH patients (20%) with a hernia sac with an overall survival of 93% vs 73% for CDH newborns without a sac (p < 0.001). Twenty-three percent of patients with a CDH sac required diaphragm patch repair vs 44% patients without a sac (p < 0.001). Pulmonary hypertension was manifested in 44% of CDH babies with a hernia sac vs 64% without a sac (p < 0.001). Three studies compared ECMO requirement: 15% with a hernia sac and 34% without sac, p < 0.001.Conclusion: This study shows significant survival benefits in newborns associated with presence of a CDH sac. This may be likely related to these infants having more favourable physiology with less severe pulmonary hypertension and/or smaller anatomical defects requiring primary closure only. What is Known: • Early reports have suggested survival benefits associated with a hernia sac in CDH. • Previous studies have included only a small number of patients. What is New: • A systematic review of published studies clearly shows that CDH newborns with a hernia sac have better overall survival outcomes and less severe pulmonary hypertension. • ECMO utilization and patch repair were also less often required in newborns with a hernia sac.

Necrotising enterocolitis-A 15-year outcome report from a UK specialist centre.

AIMS: Necrotising enterocolitis (NEC) is a disease associated with high mortality and morbidity, low birthweight and prematurity are risk factors. This study reports outcomes of babies having emergency laparotomy for NEC, examining institutional trends and exploring impact of multiple variables on mortality at 30 days and 1 year post-operatively. METHODS: Case records of babies with ICD coding for NEC were examined from 2000 to 2015. After exclusions, 243 cases were identified-confirmed by operative findings and histology. Cohort demographics and trends in mortality were investigated, and the relationship of common variables to mortality was modelled with univariate and multivariate logistic regression to generate a mortality prediction tool. RESULTS: Mean gestational age was 28 + 4 weeks. A 30-day mortality was 18.9%. Gestation, birthweight and area of bowel affected were significant of outcome (mortality), and the presence of pre-operative pneumoperitoneum was strongly correlated. Year of surgery and congenital cardiac pathology requiring intervention were not significant. Using multivariate regression modelling, a mortality outcome prediction tool has been developed. CONCLUSION: Good survival following operation for NEC (>70%) is feasible, even in those babies born extremely premature (<28 weeks) and post-operatively re-located to tertiary NICUs. With increasing gestational age (>32 weeks), mortality is uncommon.

Diagnostic and management strategies for congenital H-type tracheoesophageal fistula: a systematic review.

BACKGROUND: H type tracheoesophageal fistula (H-TEF) is a rare congenital anomaly. Management may be complicated by late diagnosis and variation(s) in the therapeutic strategy. A systematic review of published studies explores the utility of diagnostic studies, operations and postoperative complications. METHODS: Medline and PubMed database(s) were searched for ALL studies reporting H-TEF during 1997-2020. Using PRISMA methodology, manuscripts were screened for eligibility and reporting. RESULTS: Forty-seven eligible studies were analysed. Primary diagnosis varied widely with surgeons performing oesophagography and trachea-bronchoscopy. Preoperative localisation techniques included fluoroscopy, guidewire placement and catheterisation. A cervical approach (209 of 272 cases), as well as thoracotomy, thoracoscopy and endoscopic fistula ligation, were all described. Morbidity included fistula recurrence (1.7%), leak (2%), tracheomalacia (3.4%) and respiratory sequelae (1%). The major adverse complication in all studies was vocal cord palsy secondary to laryngeal nerve injury (18.5%) yet strikingly few centres routinely reported undertaking vocal cord screening pre or postoperatively. CONCLUSION: This study shows that paediatric surgeons record low volume activity with H type tracheoesophageal fistula. Variation(s) in clinical practice are widely evident. Laryngeal nerve injury and its subsequent management warrant special consideration. Care pathways may offset attendant morbidity and define 'best practice.'

Surgical management and outcomes of paediatric ovarian tumours-a 25-year UK single centre experience.

BACKGROUND: Ovarian neoplasms in children are rare heterogeneous lesions with variable biological behaviour and outcome. We herein report a 25-year experience from a UK specialist centre managing paediatric ovarian tumours. METHODS: All female patients requiring operation for ovarian tumours were identified during the study period 1990-2018. Patient demographics, clinical presentation, and management are highlighted. RESULTS: Eighty-eight females with 101 ovarian tumours including cases with synchronous and metachronous neoplasms were documented. Mean age at diagnosis was 11.8 years. Tumours were equally distributed in left and right ovary(s). Bilateral disease occurred in 11 (10.8%) patients. Eighty-six (85%) neoplasms were benign and 15 (15%) malignant requiring in addition to surgery chemotherapy and/or radiation. There were no significant difference(s) observed in maximum tumour diameter in benign vs malignant lesions. Only half of malignant tumours had positive tumour markers. Fifteen patients (15%) had ovarian lesions that were metastatic at primary presentation including a rare case of disseminated peritoneal gliomatosis. Surgical management included salpingo-oopherectomy n = 21 (21%), ovary excision n = 33 (33%), 'ovary sparing' tumourectomy n = 34 (34%), and cyto-reductive extirpation in 2 cases (2%). Lymphadenectomy was performed in 9 patients (9%) together with peritoneal fluid cytology in 18 cases (18%) who had abdominal ascites. Omentectomy was required in 14 patients (14%), multiple peritoneal biopsy(s)-in 11 cases (11%) and biopsy of other suspicious involved organs notably bowel, gut mesentery and contralateral ovary in 7 (7%) further patients. Recurrent and metachronous lesions occurred in 10 (10%) cases in those with teratoma (n = 9) and adenocarcinoma(s) (n = 1). Overall patient survival was 97% with only 3 deaths-mucinous cystadenocarcinoma (n = 1), desmoplastic small round cell tumour of ovarian origin (n = 1), and a small cell carcinoma of ovary with hypercalcaemia (n = 1). CONCLUSIONS: Findings from this study show an excellent survival (97%) for paediatric ovarian neoplasms. Rare malignant neoplasms though do carry a poor prognosis. In the modern era of care, all efforts should be made to preserve future hormonal health and fertility with 'ovarian sparing' operation(s) where appropriate.

Current treatment and outcomes of pediatric gastrointestinal stromal tumors (GIST): a systematic review of published studies.

Gastrointestinal stromal tumor (GIST) is a rare cancer of mesenchymal origin mostly seen in adult and elderly populations. Therefore, the prognostic and therapeutic features of pediatric GIST are not clearly defined. Clinical knowledge has been largely extrapolated from case series and adult studies. In this systematic review, we aimed to analyze the health outcome metrics of pediatric GIST. Medline and Embase databases were searched using relevant key terms. The original search retrieved 1,892 titles; 27 studies with 184 patients (68% female) were included for final review. The primary tumors were located in the stomach (165/184, 90%), small bowel (12/184, 7%), and elsewhere (7/184, 4%). Individual patient data were available in 125 cases with a median follow-up of 6.7 years. All patients underwent surgical resection, which varied from wide local excision to total gastrectomy. There were 12 deaths (10%), 65 (52%) patients were alive with no evidence of disease, and 31 cases (25%) were alive with disease. Tumor size > 5 cm, high mitotic index, and spindle morphology were predictive of mortality. Pediatric GIST has a more favorable prognosis and different characteristics versus adult tumors. There is a crucial need for international consensus and specific pediatric guidelines for the treatment of this rare tumor.

Testis-sparing surgery for testicular tumors in children: a 20 year single center experience and systematic review of the literature.

PURPOSE: Although surgical therapy for testicular tumors (TT) is often radical orchidectomy, tumor resection with preservation of healthy testicular parenchyma has been proposed. This study herein reports a 20 year single center experience applying testicular sparing surgery (TSS) as a primary operative strategy in pediatric patients. A systematic literature review summarizes the utility and outcomes of TSS in appropriately selected patients. METHODS: Pediatric patients with TT who underwent TSS between 1997 and 2018 were studied. TSS was indicated if patients presented evidence of adequately spared healthy testicular parenchyma on preoperative ultrasound and negative serum tumor markers. A systematic review of the literature was also performed. RESULTS: 12 cases met full inclusion criteria with 10 of 12 subjects in the prepubertal age group. Follow-up was 73 months (range 18-278 months). Only a single male patient (GSCCT) presented with early recurrence and orchidectomy was then performed. No cases of postoperative testicular atrophy were identified. Sexual maturation (Tanner stage) expected for age in each patient was documented. Review of the literature identified 34 published studies including 269 patients (94% prepubertal). Pathologic lesions here were mainly mature teratoma(s)-(62%) with a follow-up period of 4 years. Recurrent tumors were observed in only three patients (1.1%) notably two Leydig Cell Tumors and one Teratoma. Testicular atrophy reportedly occurred in only one single case (0.37%). DISCUSSION: TSS is a feasible alternative to radical orchidectomy in pediatric male patients with localized TT and negative tumor markers. Long term follow-up is essential to monitor testicular growth, puberty with sexual development and psychological male health.

Optimising the chick chorioallantoic membrane xenograft model of neuroblastoma for drug delivery.

BACKGROUND: Neuroblastoma is a paediatric cancer that despite multimodal therapy still has a poor outcome for many patients with high risk tumours. Retinoic acid (RA) promotes differentiation of some neuroblastoma tumours and cell lines, and is successfully used clinically, supporting the view that differentiation therapy is a promising strategy for treatment of neuroblastoma. To improve treatment of a wider range of tumour types, development and testing of novel differentiation agents is essential. New pre-clinical models are therefore required to test therapies in a rapid cost effective way in order to identify the most useful agents. METHODS: As a proof of principle, differentiation upon ATRA treatment of two MYCN-amplified neuroblastoma cell lines, IMR32 and BE2C, was measured both in cell cultures and in tumours formed on the chick chorioallantoic membrane (CAM). Differentiation was assessed by 1) change in cell morphology, 2) reduction in cell proliferation using Ki67 staining and 3) changes in differentiation markers (STMN4 and ROBO2) and stem cell marker (KLF4). Results were compared to MLN8237, a classical Aurora Kinase A inhibitor. For the in vivo experiments, cells were implanted on the CAM at embryonic day 7 (E7), ATRA treatment was between E11 and E13 and tumours were analysed at E14. RESULTS: Treatment of IMR32 and BE2C cells in vitro with 10 µM ATRA resulted in a change in cell morphology, a 65% decrease in cell proliferation, upregulation of STMN4 and ROBO2 and downregulation of KLF4. ATRA proved more effective than MLN8237 in these assays. In vivo, 100 µM ATRA repetitive treatment at E11, E12 and E13 promoted a change in expression of differentiation markers and reduced proliferation by 43% (p < 0.05). 40 µM ATRA treatment at E11 and E13 reduced proliferation by 37% (p < 0.05) and also changed cell morphology within the tumour. CONCLUSION: Differentiation of neuroblastoma tumours formed on the chick CAM can be analysed by changes in cell morphology, proliferation and gene expression. The well-described effects of ATRA on neuroblastoma differentiation were recapitulated within 3 days in the chick embryo model, which therefore offers a rapid, cost effective model compliant with the 3Rs to select promising drugs for further preclinical analysis.

Management of paediatric high-grade blunt renal trauma: a 10-year single-centre UK experience.

OBJECTIVE: To report the management and outcome of paediatric patients sustaining high-grade blunt renal trauma. PATIENTS AND METHODS: Medical records were examined for all American Association for the Surgery of Trauma (AAST) grade III-V blunt renal trauma cases admitted to a paediatric trauma centre from 2005 to 2015. Data collected and analysed included: demographics, imaging modalities, management, length of hospital stay (LOS), complications, and follow-up outcomes. RESULTS: In all, 18 children (12 boys, six girls) with mean (range) age 11 (4-15) years were included. According to the AAST grading criteria, 39% (seven of 18) of the patients had grade III, 50% (nine of 18) grade IV, and 11% (two of 18) grade V injuries; 44% (eight of 18) had concomitant injuries. Most of the patients were managed conservatively (89%, 16 of 18), although two of the 16 subsequently needed JJ-stent insertion during inpatient stay for symptomatic urinoma(s). In all, 11% (two of 18) of the patients required interventional radiology service(s), involving selective embolisation for life-threatening renal tract haemorrhage. Blood transfusion for renal injury exclusively was required in 11% (two of 18) of the patients. In all, 89% (16 of 18) of the patients had at least one follow-up imaging study before hospital discharge; most (13 of 16) had ultrasonography and three required computed tomography. The median (range) LOS was 11 (4-31) days. In all, 17% (three of 18) of the patients required hospital re-admission within 30 days for complications and all required interventional procedures: JJ stent for urinoma (one), embolisation of renal arterio-venous fistula (one), and embolisation for a post-traumatic pseudoaneurysm (one). Overall, the median (range) follow-up was 6 (2-60) months. In all, 78% (14 of 18) of the patients had dimercaptosuccinic acid studies, with 11 showing reductions in renal function (range 3-44%). CONCLUSIONS: This study supports a care pathway strategy advocating conservative management of high-grade renal injuries in children. However, patients may experience a relative decline in renal function with higher grade injuries indicating the need for monitoring and follow-up.

Angiomatoid fibrous histiocytoma: A case of local recurrence and metastases to loco-regional lymph nodes that responded to chemotherapy.

Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue tumour with intermediate malignant potential. We report the case of a patient with local recurrence of AFH in two locations and lymph node metastases 18 months after primary surgical excision. The patient was treated with six cycles of ifosfamide and doxorubicin chemotherapy and a further three courses of ifosfamide monotherapy. Reassessment imaging showed a good response to chemotherapy with reduction in size of the two tumours of local recurrence and the lymph node metastases. This case demonstrates that AFH can respond to chemotherapy, even though it is rarely used.