Katrina J. Sullivan

Congenital mesoblastic nephroma: a study of 19 cases using immunohistochemistry and ETV6-NTRK3 fusion gene rearrangement

Mesoblastic nephroma (MN) is the most common renal tumour in the first 3 months of life and accounts for 3-5% of all paediatric renal neoplasms. To further understand the morphological variants of MN, we identified 19 cases of MN (five classic, eight cellular and six mixed) and examined each case for markers known to be important in urogenital embryological development (PAX8, WT1 and RCC), stem cell associated markers (Oct 4, CD34 and c-kit), muscle/myofibroblastic markers (muscle specific actin, calponin and h-caldesmon), aberrant transcription factors, cell cycle regulation and other oncogenic proteins (p16, cyclin D1 and beta-catenin). Fluorescence in situ hybridisation (FISH) testing for ETV6-NTRK3 gene fusion/rearrangement revealed further differentiation between the subtypes with ETV6-NTRK3 gene fusion detected in 0/5 of the classic MN, 8/8 of the cellular MN and 5/6 of the mixed MN cohorts, respectively. Our results conclude that cyclin D1 and beta-catenin may be useful markers for differentiating between cellular MN and classic MN when the histology is not conclusive. The absence of expression of stem cell markers and markers involved in urogenital development suggests that MN is not a nephroma and most likely represents a soft tissue tumour, with congenital infantile fibrosarcoma representing cellular MN with a predilection to arise in the kidney. In addition, the immunophenotype and genetic fingerprint of mixed MN most likely represents a heterogenous group of tumours that are mostly cellular type, with areas that are phenotypically less cellular.

Feeding Post-Pyloromyotomy: A Meta-analysis.

CONTEXT: Postoperative emesis is common after pyloromyotomy. Although postoperative feeding is likely to be an influencing factor, there is no consensus on optimal feeding. OBJECTIVE: To compare the effect of feeding regimens on clinical outcomes of infants after pyloromyotomy. DATA SOURCES: Cumulative Index to Nursing and Allied Health Literature, The Cochrane Central Register of Controlled Trials, Embase, and Medline. STUDY SELECTION: Two reviewers independently assessed studies for inclusion based on a priori inclusion criteria. DATA EXTRACTION: Data were extracted on methodological quality, general study and intervention characteristics, and clinical outcomes. RESULTS: Fourteen studies were included. Ad libitum feeding was associated with significantly shorter length of stay (LOS) when compared with structured feeding (mean difference [MD] −4.66; 95% confidence interval [CI], −8.38 to −0.95; P = .01). Although gradual feeding significantly decreased emesis episodes (MD −1.70; 95% CI, −2.17 to −1.23; P < .00001), rapid feeding led to significantly shorter LOS (MD 22.05; 95% CI, 2.18 to 41.93; P = .03). Late feeding resulted in a significant decrease in number of patients with emesis (odds ratio 3.13; 95% CI, 2.26 to 4.35; P < .00001). LIMITATIONS: Exclusion of non-English studies, lack of randomized controlled trials, insufficient number of studies to perform publication bias or subgroup analysis for potential predictors of emesis. CONCLUSIONS: Ad libitum feeding is recommended for patients after pyloromyotomy as it leads to decreased LOS. If physicians still prefer structured feeding, early rapid feeds are recommended as they should lead to a reduced LOS.

The value of preoperative liver biopsy in the diagnosis of extrahepatic biliary atresia: A systematic review and meta-analysis

BACKGROUND In extrahepatic biliary atresia (EHBA) obstruction of the biliary tree causes severe cholestasis leading to cirrhosis and death if left untreated in a timely manner. Infants with cholestasis may undergo many tests before EHBA diagnosis is reached. The role and place of preoperative liver biopsy in the diagnostic paradigm for EHBA have not been established. METHODS We conducted a systematic review of MEDLINE, Embase, and CENTRAL to obtain all publications describing the sensitivity/specificity/accuracy/positive predictive value (PPV)/negative predictive value (NPV) of preoperative liver biopsy in infants with cholestasis. Screening, data extraction, and quality assessment were done in duplicate. Extracted data are described narratively and analyzed using forest plots and receiver operating characteristic curves. RESULTS A total of 22 articles were included. Overall, the pooled accuracy of preoperative liver biopsy was 91.7%, with a sensitivity of 91.2%, specificity of 93.0% (n=1231), PPV of 91.2%, NPV of 92.5% (n=1182), and accuracy of 91.6% (n=1106). In patients who were 60days or less at time of presentation or diagnosis, the pooled sensitivity, specificity, PPV, NPV, and accuracy were 96.4%, 96.3%, 95.8%, 96.3%, and 94.9%, respectively. CONCLUSION Quantitative analysis demonstrated preoperative biopsy to be both highly specific and sensitive in diagnosing EHBA preoperatively. It is a highly reliable test that offers a means of arriving at an early definitive diagnosis of EHBA.

Histologic analysis of eosinophils and mast cells of the gastrointestinal tract in healthy Canadian children.

Many gastrointestinal (GI) disorders, including GI eosinophilia and inflammatory bowel disease, can be characterized by increased mucosal eosinophils (EOs) or mast cells (MCs). Normal mucosal cellular counts along the GI tract in healthy children have not been established for a Canadian pediatric population. To establish a benchmark reference, we quantified EO and MC from 356 mucosal biopsies of the GI tract obtained during upper and lower endoscopic biopsies of 38 pediatric patients in eastern Ontario. Mean total counts of EO varied for the 11 tissues we examined, from a low of 7.6±6.5/high-power field (HPF) (×40 [×400, 0.55mm(2)]) in the body of the stomach to a high of 50.3±17.4/HPF in the cecum. The lower GI tract (ileum, cecum, colon, sigmoid, and rectum) generally had higher total EO counts than the upper GI tract (antrum and body of stomach, duodenum, and duodenal cap) (combined average of 32.1±20.6 versus 19.3±15.8, respectively). Similarly, the number of mucosal MC was different in the various regions of the GI tract ranging from 0.04±0.2/HPF in the duodenal cap to 0.9±2.6/HPF in the ileum. Total counts for EO and MC in the lamina propria were not significantly different between sexes when adjusted for multiple testing. EO polarity was absent in many cases, irrespective of the GI region. These numeration and localization of EO and MC will provide normative data for upper and lower endoscopic GI biopsies in the pediatric population of Eastern Ontario.

Optimal age for elective surgery of asymptomatic congenital pulmonary airway malformation: a meta-analysis

Controversy exists on the optimal age for elective resection of asymptomatic congenital pulmonary airway malformation. Current recommendations vary widely, highlighting the overall lack of consensus. A systematic search of Embase, MEDLINE, CINAL, and CENTRAL was conducted in January 2016. Identified citations were screening independently in duplicate and consensus was required for inclusion. Results were pooled using inverse variance fixed effects meta-analysis. Meta-analysis results indicate no statistically significant differences for complications within the 3-month and 6-month age comparison groups [odds ratio (OR) 4.20, 95% confidence interval (CI) 0.78–22.77, I2 = 0%; OR 2.39, 95% CI 0.63–9.11, I2 = 0%, respectively]. Older patients were significantly favoured for 3-month and 6-month age comparison groups for length of hospital stay [mean difference (MD) 4.13, 95% CI 2.31–5.96, I2 = 0%; MD 3.38, 95% CI 0.44–6.31, I2 = 0%, respectively]. Borderline statistical significance was observed for chest tube duration in patients ≥6 months of age (MD 1.06, 95% CI 0.02–2.09, I2 = 0%). No mortalities were recorded. Surgical treatment appears to be safe at all ages, with no mortalities and similar rates of complications between age groups. The included evidence was not sufficient to make a conclusive recommendation on optimal age for elective resection.

Value of histopathology for predicting the post-operative complications of ileo-anal anastomosis (J-pouch) procedure in children with refractory ulcerative colitis.

The J-pouch is a surgical procedure offered to children with refractory ulcerative colitis (UC) who have undergone subtotal colectomy to reconstruct a reservoir function with ileo-anal anastomosis. Unfortunately, post-operative complications may occur and can compromise the pouch function. We assessed rectal histopathology to determine whether severity of inflammation in the rectum prior to the creation of the J-Pouch was associated with post-operative complications. We retrospectively reviewed the histopathology of all J-pouch procedure specimens from paediatric patients during the period 2000-2013 using an objective grading system that assesses the chronicity and activity of the UC disease. We analysed the parameters for association with the post-operative complications. A classification tree algorithm was generated to predict the risk of complication based on histopathological parameters. A total of 28 paediatric patients were identified, among whom 10 developed post-operative complications (35%). The activity score at the recto-anal margin was higher among the patients with post-operative complications (mean 7.3±3.1 versus 4.8±3.1; p=0.04). The involvement of more than 5% colonic crypts with epithelial neutrophilic infiltration at the recto-anal margin was found to be an independent parameter that would stratify the patients into low-risk or high-risk group for developing complications (17% versus 64%; p=0.04). An association between UC disease activity at the recto-anal margin and post-operative J-pouch complications was determined. Potentially, this association suggests that a histopathological assessment of the recto-anal transitional zone may have value in guiding the surgeon on the risk of post-operative complications.

Assessing quality of life of patients with hypospadias: A systematic review of validated patient-reported outcome instruments

BACKGROUND Patient-reported outcomes have the potential to provide invaluable information for evaluation of hypospadias patients, aid in decision-making, performance assessment, and improvement in quality of care. To appropriately measure patient-relevant outcomes, well-developed and validated patient-reported outcome (PRO) instruments are essential. OBJECTIVE To identify and evaluate existing PRO instruments designed to measure quality of life and/or satisfaction of individuals with hypospadias that have been developed and validated in a hypospadias population. METHODS A systematic search of MEDLINE, EMBASE, PsycINFO, CINAHL and Health and Psychosocial Instruments was conducted in April 2016. Two reviewers independently assessed studies and identified PRO instruments for inclusion. Data were extracted on study characteristics, instrument development and validation, and content domains. RESULTS A total of 32 studies were included that used or described five PRO instruments: Hypospadias Objective Scoring Evaluation (HOSE), Pediatric Penile Perception Score (PPPS), Penile Perception Score (PPS), Genital Perception Scale (GPS) for adults, and GPS for children/adolescents. Instrument development and validation was limited. The majority of identified instruments focused on postoperative cosmetic satisfaction, with only one instrument considering urinary function, and no instruments evaluating sexual function and psychosocial sequelae. CONCLUSIONS While many hypospadias studies have acknowledged the necessity of a patient-reported element, few have used validated PRO instruments developed in a hypospadias population. Existing instruments to measure patient-reported outcomes in hypospadias require improvement in both the breadth of content and in their development and validation methodology.

Validation of algorithms to determine incidence of Hirschsprung disease in Ontario, Canada: a population-based study using health administrative data

Objective Incidence rates of Hirschsprung disease (HD) vary by geographical region, yet no recent population-based estimate exists for Canada. The objective of our study was to validate and use health administrative data from Ontario, Canada to describe trends in incidence of HD between 1991 and 2013. Study design To identify children with HD we tested algorithms consisting of a combination of diagnostic, procedural, and intervention codes against the reference standard of abstracted clinical charts from a tertiary pediatric hospital. The algorithm with the highest positive predictive value (PPV) that could maintain high sensitivity was applied to health administrative data from April 31, 1991 to March 31, 2014 (fiscal years 1991–2013) to determine annual incidence. Temporal trends were evaluated using Poisson regression, controlling for sex as a covariate. Results The selected algorithm was highly sensitive (93.5%) and specific (>99.9%) with excellent predictive abilities (PPV 89.6% and negative predictive value >99.9%). Using the algorithm, a total of 679 patients diagnosed with HD were identified in Ontario between 1991 and 2013. The overall incidence during this time was 2.05 per 10,000 live births (or 1 in 4,868 live births). The incidence did not change significantly over time (odds ratio 0.998, 95% confidence interval 0.983–1.013, p = 0.80). Conclusion Ontario health administrative data can be used to accurately identify cases of HD and describe trends in incidence. There has not been a significant change in HD incidence over time in Ontario between 1991 and 2013.

Value of upper endoscopic biopsies in predicting medical refractoriness in pediatric patients with ulcerative colitis

Refractory ulcerative colitis (UC) occurs in patients who experience a severe disease manifestation that is unresponsive to medical therapy. The assessment of upper endoscopic microscopic findings and its correlation with refractory UC has not been fully studied in pediatric patients and is the focus of this study. Medical records of UC patients treated at a tertiary pediatric center between 2000 and 2014 were reviewed. Endoscopic biopsies of the upper gastrointestinal (GI) tract of patients meeting a priori inclusion criteria were compared between refractory UC patients and nonrefractory UC patients for active inflammation. Statistically significant differences were determined between groups, and tissues shown to have significant differences were further evaluated for their diagnostic performance. A total of 52 patients were included, 26 in each group. Significant differences were observed in intraepithelial neutrophil infiltration and percentage involvement of crypts/glands for the antrum, body, and duodenal bulb (P ≤ .001, .005, and .01 [intraepithelial neutrophil infiltration] and P = .001, .009, and .015 [% involvement], respectively). Microabscesses of mucosal glands/crypts were also experienced in a greater number of refractory UC patients in the stomach (ie, antrum and/or body of stomach; P = .005) and duodenum (ie, duodenum and/or duodenal bulb; P = .023). The sensitivity and specificity of upper GI tissues to predict refractory UC were moderate, with sensitivities ranging from 38% to 67% and specificities ranging from 81% to 100%. Our results suggest that children with refractory UC are more likely to have active inflammation in the upper GI tract, and thus, this may represent a predictor of responsiveness to current medical therapy.