Elliot C. Pennington

Use of mechanical bowel preparation and oral antibiotics for elective colorectal procedures in children: Is current practice evidence-based?

PURPOSE It is well established through randomized trials that oral antibiotics given with or without a mechanical bowel preparation (MBP) prior to colorectal procedures reduce complications, while MBP given alone provides no benefit. We aimed to characterize trends surrounding bowel preparation in children and determine whether contemporary practice is evidence-based. METHODS Retrospective analysis of patients undergoing colorectal procedures at 42 childrens hospitals (1/2/2007-12/31/2011) was performed. Patients were analyzed for diagnosis, pre-admission status, and inpatient bowel preparation. Bowel preparation was considered evidence-based if oral antibiotics were utilized with or without a MBP. RESULTS 49% of all patients were pre-admitted (n=5,473), and the most common diagnoses were anorectal malformations (55%), inflammatory bowel disease (26%), and Hirschsprungs Disease (19%). The most common preparation approaches were MBP alone (54.3%), MBP+oral antibiotics (18.8%), and oral antibiotics alone (4.2%), although significant variation was found in hospital-specific rates for each approach (MBP alone: 0-96.1%, MBP+oral antibiotics: 0-83.6%, orals alone: 0-91.6%, p<0.0001). Only 22.9% of all patients received an evidence-based preparation (range by hospital: 0-92.3%, p<0.0001), and this rate decreased significantly during the five-year study period (27.6% in 2007 vs. 17.3% in 2011, p<0.0001). CONCLUSION According to the best available clinical evidence, less than a quarter of all children pre-admitted for elective colorectal procedures receive a bowel preparation proven to reduce infectious complications.

Targeted quantitative amniotic cell profiling: A potential diagnostic tool in the prenatal management of neural tube defects

PURPOSE We sought to determine whether amniotic cell profiles correlate quantitatively with neural tube defect (NTD) type and/or size. METHODS Sprague-Dawley fetuses exposed to retinoic acid (n=61) underwent amniotic fluid sample procurement before term. Samples were analyzed by flow cytometry for the presence of cells concomitantly expressing Nestin and Sox-2 (neural stem cells, aNSCs), and cells concomitantly expressing CD29 and CD44 (mesenchymal stem cells, aMSCs). Statistical analysis included ANOVA and post-hoc Bonferroni adjusted comparisons (P<0.05). RESULTS There was a statistically significant increase in the proportion of aNSCs in fetuses with spina bifida (6.78%± 1.87%) when compared to those with exencephaly (0.64%± 0.23%) or with both spina bifida and exencephaly (0.22%± 0.09%). Conversely, there was a statistically significant decrease in the proportion of aMSCs in fetuses with exencephaly, either isolated (1.09%± 0.42%) or in combination defects (2.37%± 0.63%) when compared with normal fetuses (8.83%± 1.38%). In fetuses with isolated exencephaly, there was a statistically significant inverse correlation between the proportion of aNSCs and defect size. CONCLUSIONS The proportions of neural and mesenchymal stem cells in the amniotic fluid correlate with the type and size of experimental NTDs. Targeted quantitative amniotic cell profiling may become a useful diagnostic tool in the prenatal evaluation of these anomalies.

Intra-Amniotic Delivery of Amniotic-Derived Neural Stem Cells in a Syngeneic Model of Spina Bifida

Objective: Neural stem cells (NSCs) may promote spinal cord repair in fetuses with experimental spina bifida. We sought to determine the fate of amniotic-derived NSCs (aNSCs) after simple intra-amniotic injection in a syngeneic model of spina bifida. Methods: Fetal neural tube defects were induced on 20 pregnant Lewis dams by prenatal administration of retinoic acid. Ten dams served as amniotic fluid donors for epigenetic isolation of aNSCs, which were expanded and labeled with 5-bromo-2′-deoxyuridine. The remaining 10 dams received intra-amniotic injections of the processed aNSCs, blindly in all their fetuses (n = 37) on gestational day 17 (term = E21-22). Fetuses with spina bifida underwent screening for the presence of donor aNSCs in the spinal cord at term. Results: Donor cells were identified in 93.3% of the animals with spina bifida, selectively populating the neural placode, typically in clusters, retaining an undifferentiated morphology, and predominantly on exposed neural surfaces, though some were detected deeper in neighboring neural tissue. Conclusions: The amniotic cavity can serve as a route of administration of NSCs in experimental spina bifida. Simple intra-amniotic delivery of NSCs may be a practical adjuvant to regenerative strategies for the treatment of spina bifida.

Contemporary practice among pediatric surgeons in the use of bowel preparation for elective colorectal surgery: A survey of the American Pediatric Surgical Association

PURPOSE The goal of this study was to characterize contemporary practice among pediatric surgeons in the use of mechanical bowel preparation (MBP) and oral antibiotics (OA) for elective colorectal surgery. METHODS A survey of the American Pediatric Surgical Association membership was conducted to characterize variation in the use of MBP and OA for commonly performed elective colorectal procedures in children. RESULTS Three-hundred thirteen members completed the survey. The most common approach used was MBP alone (31.1%), followed by diet modification only (26.8%), MBP combined with OA (19.6%), no preparation or dietary modification (12.2%), and OA alone (5.4%). The most common MBP used was a polyethylene glycol-based solution (92.6%), and the most common OA approach was neomycin combined with erythromycin (55.9%). Although MBP alone was the preferred approach among pediatric surgeons, the greatest relative change reported over time was in the adoption of dietary modifications only or no preparation at all. CONCLUSIONS Significant variation exists in the use of bowel preparation among pediatric surgeons. Although use of MBP alone remains the preferred approach for most procedures, an increasing number of surgeons report abandoning this approach in favor of dietary modification alone or no preparation at all.

Operative indications in recurrent ileocolic intussusception

BACKGROUND Air-contrast enema (ACE) is standard treatment for primary ileocolic intussusception. Management of recurrences is less clear. This study aimed to delineate appropriate therapy by quantifying the relationship between recurrence and need for bowel resection, pathologic lead points (PLP), and complication rates. METHODS After IRB approval, a single institution review of patients with ileocolic intussusception from 1997 to 2013 was performed, noting recurrences, outcomes, and complications. Fishers exact and t-tests were used. RESULTS Of 716 intussusceptions, 666 were ileocecal. Forty-four underwent bowel resection, with 29 PLPs and 9 ischemia/perforation. Recurrence after ACE occurred in 96 (14%). Recurrence did not predict PLP (P=0.25). Recurrence (≥3) was associated with higher resection rate (P=0.03), but not ischemia/perforation (P=0.75). ACE-related complications occurred in 4 (0.5%) patients. Successful initial ACE had 98% negative predictive value for resection and PLP (e.g., after successful ACE, 2% had resections, 2% PLP). After failed initial ACE, 36% received resection, and 23% had PLP (P<0.001). CONCLUSIONS Recurrence is associated with a greater risk of resection but not PLP or ACE-complication. Failed ACE is associated with increased risk for harboring PLP and receiving resection. ACE should be the standard treatment in recurrent intussusception, regardless of number of recurrences.

Variation in bowel preparation among pediatric surgeons for elective colorectal surgery: A problem of equipoise or a knowledge gap of the available clinical evidence?

PURPOSE Despite rigorous data from adult literature demonstrating that oral antibiotics (OA) reduce infectious complications and mechanical bowel preparation (MBP) alone does not, MBP alone remains the preferred approach among pediatric surgeons. We aimed to explore the nature of this discrepancy through a survey of the American Pediatric Surgical Association membership. METHODS Surgeons were queried for their choice of bowel preparation, factors influencing their practice, and their impression of the strength and relevance of the adult literature to pediatric practice. RESULTS Surgeons who used MBP alone (31%) cited a reduction in stool burden and infectious complications as important factors, whereas surgeons choosing not to use OA (70%) reported a lack of benefit in reducing infectious complications as the primary reason. Although 53% of surgeons reported that evidence from adult literature was the most important influence, 73% of surgeons reported there was poor evidence supporting the use of OA (±MBP), and only 25% used a preparation supported by adult randomized data. CONCLUSIONS Wide variation exists among pediatric surgeons in the perceived utility of MBP and OA. Although the majority of pediatric surgeons cited the adult literature as the strongest influence on their practice, this is not consistent with stated perceptions or practice.

The Impact of Gestational Age on Targeted Amniotic Cell Profiling in Experimental Neural Tube Defects

Purpose: The proportions of select stem cells in term amniotic fluid have been shown to correlate with the type and size of experimental neural tube defects (NTDs). We sought to determine the impact of gestational age upon this form of targeted amniotic cell profiling. Methods: Sprague-Dawley fetuses with retinoic acid-induced NTDs (n = 110) underwent amniotic fluid procurement at four time points in gestation. Samples were analyzed by flow cytometry for the presence of cells concomitantly expressing Nestin and Sox-2 (neural stem cells, aNSCs) and cells concomitantly expressing CD29 and CD44 (mesenchymal stem cells, aMSCs). Statistical analysis was by nonparametric Kruskal-Wallis ANOVA (p < 0.05). Results: There was a statistically significant impact of gestational age on the proportions of both aMSCs (p = 0.01) and aNSCs (p < 0.01) in fetuses with isolated spina bifida. No such impact was noted in normal fetuses (p > 0.10 for both cells), in isolated exencephaly (p > 0.10 for both cells), or in combination defects (p > 0.10 for both cells). Gestational age had no effect on aNSC/aMSC ratios. Conclusions: Targeted quantitative amniotic cell profiling varies with gestational age in experimental isolated spina bifida. This finding should be considered prior to the eventual translation of this diagnostic adjunct into the prenatal evaluation of these anomalies.