Acute pancreatitis in childhood - a comparative international study and tale of two cities.

BACKGROUNDS: To compare factor(s) contributing to aetiology, management and clinical outcome(s) of paediatric patients acquiring acute pancreatitis (AP) at two major university paediatric surgical centres in Liverpool and Bangkok. METHODS: All patients (<18 years) with an index diagnosis of AP (ICD 10 coding) during 2006-2016 were studied. RESULTS: 121 patients included n = 79 (65.3%) in Thailand versus n = 42 (34.7%) in the UK centre with no difference(s) in age at diagnosis at 10.4 ± 4.5 and 11.7 ± 6 years. (P = 0.12). Major AP aetiology(s) in Thailand were medications (39.2%) and choledochal cysts (8.9%). In the UK-gallstone disease (21.4%), and medications (16.7%) were leading factors (P < 0.01). Ultrasonography was deployed more frequently in the UK versus Thai centre (74.3% vs. 49.1%; P < 0.01). Pancreatitis was confirmed by imaging in 67.9% (Thai) and 62.9% (UK) patients (P = 0.47). Most patients at both centres had a mild-grade pancreatitis illness (95% Thai vs. 90.5% UK; P = 0.28) while 12.7% of Thai and 19% of UK children developed pancreatitis-related complication (P = 0.37). Overall mortality rate (%) was significantly higher in the Thai versus UK centre (27.8% vs. 9.5%; P = 0.02). CONCLUSIONS: Aetiology of acute pancreatitis appears to vary between UK and Thailand children. Timely early diagnosis and healthcare pathways may be driven by local patient-related factor(s). The higher mortality (%) observed in Thailand versus UK in this comparative study was linked to underlying co-existent chronic medical condition(s) in vulnerable patient cohorts.

Developing balloon dilatation sizing guidance for anastomotic stricture dilatation following oesophageal atresia repair.

PURPOSE: To develop guidance for the selection of balloon catheter size when performing an oesophageal dilatation for a stricture post oesophageal atresia repair. METHODS: This was a single centre retrospective study at a paediatric tertiary centre. Dilatations were performed between 2015 and 2020. All dilatations were performed under general anaesthesia using balloon catheters under fluoroscopic guidance. Outliers were excluded using ROUT method and descriptive analysis was calculated to 1SD or IQR depending on the normality of data distribution. RESULTS: 97 patients underwent 341 dilatations. Median age was 19 months (37 weeks corrected gestation-17 years), median weight was 10.7 kg (2.6-72 kg). Balloon catheter sizes ranged from 6-8 mm to 18-20 mm. There was strong correlation between weight and balloon size (r = 0.8, p < 0.0001). There were 2 perforations (0.6%), both diagnosed intra-operatively and treated conservatively. From the results, weight recommendations were created for each balloon size. CONCLUSION: Fluoroscopic balloon dilatation is a safe and effective method to treat anastomotic stricture following oesophageal atresia repair. Previous studies have shown correlation between patient weight and oesophageal diameter. We propose guidance for using an appropriate balloon size based on patient's weight with the aim to reduce complication.

Long-term functional outcomes of sacrococcygeal teratoma - A systematic review of published studies exploring 'real world' outcomes.

Sacrococcygeal teratoma (SCT) is a rare neoplasm affecting 1:35,000 newborns. Long-term follow-up from small observational studies report impaired bladder/bowel function. This current study comprehensively analyses all published studies to better define true long-term functional sequelae. Medline/Embase databases were searched with PRISMA guidelines. Final analysis yielded 37 studies involving 1116 patients (854 female; 77%). Individual datasets were available in 14 studies (222 patients). According to Altman classification - 298/845 (35%) were Type I, 252/845 (30%) Type II, 133/845 (16%) Type III, and 128/845 (15%) Type IV tumours. Most neoplasms were benign (640/858; 75%), 77/858 (9%) immature and 141/858 (16%) malignant. Abnormal bladder function was reported in 7/39 (18%) Altman Type I, 23/61 (37.7%) Type II, 11/34 (32.4%) Type III, and 15/25 (60%) Type IV cases (p = 0.007). Adverse urological outcomes were notably common in immature/malignant neoplasms vs benign tumours and in patients requiring reoperation(s); p = 0.002 and p = 0.01. Bowel dysfunction was evident in 19% index cases and constipation in 26% with no significant association(s) with tumour characteristics. Higher Altman stage, unfavourable tumour biology and reoperation are associated with poor functional outcome(s). Multidisciplinary management from primary diagnosis of SCT is crucially important for all patients to best optimise functional outcomes across surgical specialities.

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.

Routine evaluation of vesico-ureteric reflux in children with anorectal malformation does not reduce the rate of urinary tract infection.

OBJECTIVE: Children with anorectal malformations (ARM) have a high rate of renal anomalies and increased risk of urinary tract infection (UTI). We aimed to determine whether using routine Micturating Cystourethrogram (MCUG) to detect VUR is effective in reducing the incidence of UTI or renal scarring in children with ARM. METHODS: A retrospective study of consecutive children diagnosed with ARM in two centres with a minimum of 3 years follow-up was performed, excluding those with cloaca or an MCUG prior to ARM repair. Univariate and multivariate logistic regression analysis was used to determine variables which were associated with VUR, UTI and renal scarring. Associations are described as Odd's Ratio (OR), 95% Confidence Interval. Significance was taken as p<0.05. RESULTS: 344 children were included with a median age of 8 years (IQR 5-11 years). 150 (44%) were female. 89 (26%) had renal anomalies and 101 (29%) had spine anomalies. 148 patients had routine MCUG and VUR was found in 62 (42%) of these children. Univariate analysis did not correlate any of the assessed variables with VUR or renal scarring. However, abnormal renal ultrasound - OR 6.18 (95% CI 2.99-13.07, p 0.0001) was associated with UTI whilst abnormal spine - OR 0.27 (95% CI 0.10-0.62, p 0.009), low ARM - OR 0.30 (CI 0.14-0.63, p 0.006) and intermediate ARM - OR 0.35 (CI 0.17-0.70, p 0.01) were associated with a reduced risk of UTI. On multivariate analysis, only abnormal renal USS retained a significant association with UTI (p<0.0001). CONCLUSIONS: VUR is common in patients with ARM. Children with an abnormal R-USS are at increased risk of UTI. Performing routine MCUG does not reduce the risk of UTI in children with ARM.

Neuroblastoma: the association of anatomical tumour site, molecular biology and patient outcomes.

BACKGROUND: Numerous factors have been identified as carrying prognostic value in neuroblastoma (NB) and therefore incorporated in risk stratification of disease. Here, we investigate the association of anatomical site of NB with molecular biology and clinical outcomes. METHODS: A total of 117 patients with NB were studied over a 30-year period. Tumour location was confirmed with computed tomography/magnetic resonance imaging. Data on molecular biology were obtained as testing became available. Chi-squared, Fisher's exact test and Kaplan-Meier log-rank tests were used for statistical analysis. RESULTS: Tumour originated in the thoracic region (thoracic NB, TNB) in 15 patients (13%), adrenal gland (adrenal NB, ANB) in 88 patients (75%) and abdominal/paravertebral chain (paravertebral NB, PVNB) in 14 patients (12%). Overall survival (OS) for ANB was significantly lower (38%; P = 0.015). ANB cases were more frequently diagnosed at stage IV (69%; P = 0.001). MYCN amplification was noted in 33% of ANB cases and associated with lower OS (17% versus 62% MYCN non-amplified ANB; P = 0.01). The vast majority of TNB and PVNB were non-MYCN amplified (100% and 86%, respectively) and carried better prognosis (OS 86% and 83%, respectively). Forty-two percent of ANB cases were diploid and had lower OS (20% versus 71% hyperdiploid ANB; P = 0.079). TNB and PVNB were found to be mostly hyperdiploid (86% and 100%, respectively) with better OS (83% and 33%, respectively). Segmental chromosomal alterations had prognostic significance in those with PVNB (P = 0.03). CONCLUSION: TNB tumours have better outcomes than adrenal tumours. This may be due to varied factors reported here including non-metastatic disease at presentation, non-amplification of the MYCN oncogene and overall favourable molecular biology characteristics.

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.

Quality of systematic reviews and meta-analyses published in pediatric surgery.

AIMS: Systematic reviews (SRs) and meta-analyses (MAs) studies may influence and direct surgical practice. Against this background we have analyzed the quality of systematic reviews and meta-analyses published in the specialty field of pediatric surgery using the Assessment of Multiple Systematic Reviews 11-item tool (AMSTAR). METHODS: MEDLINE and EMBASE databases and the three major journals in pediatric surgery were searched for SRs and MAs in pediatric surgery. Studies involving predominantly adult populations were excluded. Two reviewers independently scored included studies against AMSTAR criteria and disagreements were resolved by consensus. A total rating of 4 or less was considered 'poor' methodological quality, 5-8 as 'fair to good' and 9 or greater as 'good'. RESULTS: Original searching retrieved 1,281 articles. 126 articles were included for final analysis. Examining recent trends, 4 studies were published in 1995-2000 compared to 78 in 2011-2014. Using AMSTAR scoring criteria, 35 reviews (28%) were regarded as 'poor' in terms of methodological quality, 59 (47%) 'fair', and 32 (25%) 'good' quality. We observed no improvement in AMSTAR score before and after the development of the tool (mean score pre-2008 6.8, post-2008 5.9, p = 0.136). CONCLUSIONS: Despite an increase in the number of SRs / MAs published in pediatric surgery, a quarter of all studies were considered poor in terms of their quality and scientific validity. Journals must define and apply minimum criteria to ensure pediatric surgeons seeking to publish high quality SRs / MAs achieve these requirements.

Heterotaxy and intestinal rotation anomalies: 20 years experience at a UK regional paediatric surgery centre.

BACKGROUND: The association of heterotaxy with intestinal rotation anomalies is well described. However debate exists with regard optimal management notably should 'asymptomatic' bowel rotation anomalies undergo operation? The present study therefore sought to determine: (1) the risk(s) of volvulus in patients diagnosed with heterotaxy and (2) define morbidity associated with operation for 'asymptomatic' anomalies in a fragile patient cohort with co-existent congenital heart disease. METHODS: Medical case record reviews of ALL heterotaxy patients born during January 1993-December 2013 and attending a UK paediatric centre were analyzed. RESULTS: Of a total of 92 patients, 16 (17.4%) cases underwent foregut imaging studies. Three examinations were performed in 'symptomatic' patients. Twelve studies reported 'abnormal anatomy' with only five patients undergoing surgical correction. No complication(s) were recorded after Ladd's operation to correct defects. A single fatality occurred within 30 days postoperatively from cardiac failure. In 87 patients in whom Ladd's operation was not undertaken, no single patient developed intestinal volvulus (median length of follow-up 27.2 months, total 446.1 person years). CONCLUSION: This study strongly supports a 'watchful waiting' policy for heterotaxy patients. Many children who ultimately die from heart disease may avoid unnecessary abdominal surgery.

Open versus needle biopsy in diagnosing neuroblastoma.

BACKGROUND: Open surgical biopsy is traditionally advocated prior to initiating therapy in UKCCLG neuroblastoma protocols. We report a single centre experience comparing the utility of open biopsy vs image guided needle biopsy in aiding the definitive diagnosis and risk stratification of neuroblastoma - (Shimada classification, MYCN expression, cytogenetics - 1p 11q, 17 q). METHODS: Medical records of all new cases of neuroblastoma presenting to a single UKCCLG centre during January 2002-July 2013 were examined. RESULTS: Thirty nine patients underwent a biopsy of primary tumour for neuroblastoma during the study. Twenty one children had open biopsy and eighteen cases had a needle biopsy. Staging of neuroblastoma revealed - stage 4 (n=26), stage 3 (n=7), stage 2 (n=3) and stage 4S (n=3). Sites of primary tumour were adrenal gland (n=20), abdomen (n=12), thoracic (n=4), abdomino-thoracic (n=2) and abdomino pelvic regions (n=1). All patients (open vs needle) had adequate tissue retrieved for histological diagnosis of neuroblastoma. One needle and one open biopsy case did not have MYCN status determined despite adequate tissue sampling. Seventeen patients (7 open and 10 needle biopsies) had 1p and 17q status reported in MLPA testing (Multiplex Ligation-dependent Probe Amplification). No single patient required a repeat tumour biopsy. Morbidity in the series was minimal with only one child - open biopsy group, requiring emergent laparotomy to control bleeding from an abdominal primary tumour. No complications were recorded with needle biopsy. CONCLUSIONS: Open and image guided needle biopsy appear to yield adequate tissue sampling for diagnosis, risk classification and staging of neuroblastoma. Further larger co-operative studies may usefully guide national and international protocols.

Neuroblastoma: a 20-year experience in a UK regional centre.

PURPOSE: The role of surgery in the management of neuroblastoma yields conflicting reports. We report a 20-year experience from a UK centre in the context of evolving cancer therapies for neuroblastoma. METHODS: Hospital records of 91 neuroblastoma patients from 1985 to 2005 were studied. Patient demographics, data from operating notes and tumour biology (MYCN status) where available were analysed. RESULTS: Surgery consisted of primary resection or delayed operation following tumour biopsy/chemotherapy. Overall survival was 100% for stage 1(n = 3), 90% for stage 2 (n = 10), 46% for stage 3 (n = 13), 13% for stage 4 (n = 55) and 56% for stage 4S disease (n = 9). During the eras 1985-1994 versus 1995-2005, survival for stage 3 lesions was 25% and 80% (P = 0.04) with marginal increase in survival observed in stage 4 disease (12% vs. 22%, P = 0.083). Delayed tumour resection was not performed in 20 (36%) stage 4 patients due to progressive disease. Complete tumour resection was achieved in 62% of stage 3-4 patients during 1995-2005 compared to 38% in 1985-1994. The extent of surgical resection (complete vs. partial) showed no significant differences in overall survival or relapse rates. Postoperative morbidity occurred in 15.7% of cases emphasising technical challenges in resection of neuroblastoma. No child with MYCN amplification survived versus 59% survival in non-amplified cases (P = 0.012). CONCLUSIONS: While complete tumour resection may be desirable in advanced neuroblastoma (stage 3-4) these findings suggest that the radicality of operation is not significantly associated with better overall survival/relapse. Improving outcomes in the 1995-2005 era for patients with stage 3-4 tumours complements the introduction of new high dose-intensive chemotherapy regimens and other adjuvant therapies for this enigmatic disease.