Antithrombin III infusion improves anticoagulation in congenital diaphragmatic hernia patients on extracorporeal membrane oxygenation.

PURPOSE: Achieving effective anticoagulation during neonatal extracorporeal membrane oxygenation (ECMO) without increasing the risk of hemorrhage remains challenging. The use of antithrombin III (AT-III) for this purpose has been examined, but studies have been limited to intermittent bolus dosing. We aimed to evaluate the efficacy and safety of an institutionally developed AT-III continuous infusion protocol in neonates receiving ECMO for the treatment of congenital diaphragmatic hernia (CDH). METHODS: In this single center, retrospective study, all neonates with a CDH who received ECMO support during the study period were included. Data on anticoagulation labs and therapy, life-threatening bleeding, and circuit changes were analyzed. RESULTS: Eleven patients were divided into two groups: patients with AT-III continuous infusion (n = 5) and without (n = 6). There were no differences in the gestational age (p = 0.29), sex (p = 1.00), ECMO duration (p = 0.59), or initial AT-III levels (p = 0.76) between groups. Patients in the AT-III infusion group had on average 18.5% higher AT-III levels (p < 0.0001). Patients receiving continuous AT-III infusions spent a significantly higher percentage of ECMO time within the therapeutic range, measured using anti-Factor Xa levels (64.9±4.2% vs. 29.1±8.57%, p = 0.008), and required fewer changes to the heparin infusion rate (6.48±0.88 vs 2.38±0.36 changes/day changes/day, p = 0.005). Multivariate analysis revealed continuous infusion of AT-III did not increase the rate of intracranial or surgical bleeding (p = 0.27). CONCLUSION: AT-III as a continuous infusion in CDH neonates on ECMO provides a decreased need to modify heparin infusion and more consistent therapeutic anticoagulation without increasing the risk of life-threatening bleeding.

Murine colitis treated with multitargeted tyrosine kinase inhibitors.

BACKGROUND: Angiogenesis, a known pathogenic component of neoplastic and nonneoplastic diseases, serves as a therapeutic target. Vascular endothelial growth factor (VEGF) and angiogenesis are clinically elevated in inflammatory bowel disease. By targeting vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) with receptor tyrosine kinase inhibitors in a murine model of colitis, we hypothesize that angiogenesis will be suppressed and disease severity improved. METHODS AND METHODS: Sorafenib, sunitinib, and axitinib were administered by oral gavage in a murine model of dextran sodium sulfate (DSS) colitis. Inflammation score, microvessel density (MVD), and gene expression of VEGF, VEGFR, platelet-derived growth factor, PDGFR, Ang-2, and epidermal growth factor receptor was assessed. RESULTS: Inflammation and MVD were elevated in groups receiving DSS, but were similar between DSS-only and treatment cohorts. Unexpected weight loss was present in the gavaged groups versus DSS only. In treated groups, VEGFR was significantly decreased (P = 0.002) and VEGF gene expression trended down (P = 0.213) versus DSS only. Neither the platelet-derived growth factor/PDGFR pathway nor the alternative pathways, Ang-2 and epidermal growth factor receptor, were significantly changed from DSS control in treatment cohorts. CONCLUSIONS: This study confirms the association between inflammation and MVD. Antiangiogenic receptor tyrosine kinase inhibitors suppressed the VEGF/VEGFR pathway but the expected decrease in colonic MVD did not follow, suggesting possible involvement of other angiogenic pathway(s). In the DSS model of colitis, vehicle selection and mouse strain can impact disease response.

Health-Related Quality of Life and Parental Stress in Children With Fecal Incontinence: A Normative Comparison.

OBJECTIVE: The aim of the present study was to describe the quality of life and parenting stress associated with a child with fecal incontinence (FI). METHODS: Female caregivers (n = 170) of children of 3 to 12 years age with FI completed a broad and general measure of quality of life and a measure of parenting stress. Results were compared with proxy reports for a normative sample of healthy children. RESULTS: Caregivers of children with FI reported significantly impaired quality of life for their children and increased parenting stress in all of the respective domains relative to healthy controls. Impairments reported by caregivers were large in magnitude. Similarly, rates of parenting stress were at or greater than the 98th percentile for caregivers of children with FI. CONCLUSIONS: Children with fecal incontinence and their families are in need of interventions targeting their quality of life and the stress associated with caregiving. FI appears to be particularly stressful for caregivers who may be in need of support beyond medical management of their child's bowel. Moreover, additional refinements in disease-specific quality of life assessment are needed in this population. Such refinement would allow for more precise measurement of the quality of life processes that are unique to FI.

Extensive heterotopic gastric mucosa of the small intestine: imaging with 99mTc-sodium pertechnetate SPECT/CT enterography.

Extensive heterotopic gastric mucosa of the small intestine is a rare, but potentially life-threatening condition characterized by multifocal or long-segment heterotopic gastric mucosa within the bowel lumen that is often associated with other anomalies including malrotation and annular pancreas. Although the imaging findings are characteristic, this entity may be unrecognized due to its unusual imaging appearance and rarity. CT or MR enterography and 99mTc-sodium pertechnetate scintigraphy can provide complementary information that enables specific diagnosis and accurate assessment of disease extent. We present a case of extensive heterotopic gastric mucosa of the small intestine imaged by simultaneous, combined 99mTc-sodium pertechnetate single photon-emission computed tomography (SPECT)/CT enterography to both familiarize the reader with the condition and describe an imaging strategy that enables specific diagnosis and assists with treatment planning.

Mouse strain influences angiogenic response to dextran sodium sulfate-induced colitis.

BACKGROUND: Angiogenesis is a known pathologic factor in chronic inflammatory diseases. Regarding the murine dextran sodium sulfate (DSS) colitis model, different mouse strains produce variable clinical and inflammatory responses. We hypothesize that DSS colitis applied to diverse mouse strains will similarly elevate colonic microvessel density in parallel with inflammation, but will do so with different angiogenic profiles. MATERIALS AND METHODS: We induced DSS colitis in 129S2/SvPas, BALB/c, and C57BL/6 mice, then performed histologic and molecular analysis at day 7 to evaluate colonic inflammation and angiogenesis. RESULTS: Inflammation and microvessel density were similarly increased in DSS groups. The C57BL/6 cohort mounted a more severe colitis with 25% weight loss and greater colonic ulceration. Gene expression of angiogenic factors at baseline and in colitis groups were widely variable among strains. BALB/c mice exhibited higher angiogenic gene expression in control and DSS groups compared with other strains, specifically platelet-derived growth factor, angiopoietin-1, angiopoietin-1 (Ang-2), vascular endothelial growth factor receptor, and PDGF receptor. When evaluating the effect of DSS relative to controls, BALB/c mice were not significantly affected. 129S2/SvPas mice exhibited broad suppression of growth factors, significantly platelet-derived growth factor, Ang-2, and PDGF receptor. In contrast, C57BL/6 mice displayed increased gene expression, especially for angiopoietin-1 and Ang-2. CONCLUSIONS: Genetic heterogeneity influences the angiogenic profile elicited by DSS colitis. We demonstrate that within a model of murine colitis, mouse strain significantly affects inflammation-associated angiogenesis. These results may impact strain selection when using a colitis model focusing on inflammation and angiogenesis. Future studies to further define the angiogenesis pathway and potentially alter the disease course with targeted antiangiogenics are warranted.

VEGF blockade enables oncolytic cancer virotherapy in part by modulating intratumoral myeloid cells.

Understanding the host response to oncolytic viruses is important to maximize their antitumor efficacy. Despite robust cytotoxicity and high virus production of an oncolytic herpes simplex virus (oHSV) in cultured human sarcoma cells, intratumoral (ITu) virus injection resulted in only mild antitumor effects in some xenograft models, prompting us to characterize the host inflammatory response. Virotherapy induced an acute neutrophilic infiltrate, a relative decrease of ITu macrophages, and a myeloid cell-dependent upregulation of host-derived vascular endothelial growth factor (VEGF). Anti-VEGF antibodies, bevacizumab and r84, the latter of which binds VEGF and selectively inhibits binding to VEGF receptor-2 (VEGFR2) but not VEGFR1, enhanced the antitumor effects of virotherapy, in part due to decreased angiogenesis but not increased virus production. Neither antibody affected neutrophilic infiltration but both partially mitigated virus-induced depletion of macrophages. Enhancement of virotherapy-mediated antitumor effects by anti-VEGF antibodies could largely be recapitulated by systemic depletion of CD11b(+) cells. These data suggest the combined effect of oHSV virotherapy and anti-VEGF antibodies is in part due to modulation of a host inflammatory reaction to virus. Our data provide strong preclinical support for combined oHSV and anti-VEGF antibody therapy and suggest that understanding and counteracting the innate host response may help enable the full antitumor potential of oncolytic virotherapy.

Surgical management of complicated Crohn's disease.

Surgical management of pediatric Crohn's disease is fundamentally palliative, aiming to treat the sequalae of complicated disease while preserving intestinal length. Multidisciplinary discussion of risk factors and quality of life should take place prior to operative intervention. Though the surgical management of pediatric Crohn's disease is largely based on the adult literature, there are considerations specific to the pediatric population - notably disease and treatment effects on growth and development. Intrabdominal abscess is approached with percutaneous drainage when feasible, reserving surgical intervention for the patient who is unstable or failing medical therapy. Pediatric patients with fibrostenotic disease should be considered for strictureplasty when possible, for maximum preservation of bowel length. Patients with medically refractory Crohn's proctocolitis should be treated initially with fecal diversion without proctocolectomy.

Does Length of Extended Resection Beyond Transition Zone Change Clinical Outcome for Hirschsprung Pull-Through?

INTRODUCTION: A proximal resection margin greater than 5 cm from the intra-operative histologically determined transition zone has been deemed necessary to minimize the risk of transition zone pull-through. This extended resection may require the sacrifice of vascular supply and even further bowel resection. The impact of extended proximal resection margin on post-operative complications and functional outcomes is unclear. METHODS: A retrospective chart review of patients who underwent primary pull-through for Hirschsprung disease at a single institution between January 2008 and December 2022 was performed. An adequate proximal margin was defined by a circumferential normally ganglionated ring and absence of hypertrophic nerves. The extended margin was defined as the total length of proximal colon with normal ganglion cells and without hypertrophic nerves. Fecal incontinence severity was assessed with the Pediatric Fecal Incontinence Severity Score (PFISS). RESULTS: Eighty seven patients met criteria for inclusion. Median age at primary pull-through was 17 days (IQR 10-92 days), 55% (n = 48) of patients had an extended proximal margin (EPM) ≤ 5 cm, and 45% (n = 39) had an EPM > 5 cm. An EPM ≤5 cm was not associated with increased rates of Hirschsprung associated enterocolitis (≤5 cm 43%, >5 cm 39%, P = 0.701), diversion post pull-through (≤5 cm 10%, >5 cm 5%, P = 0.367) or reoperation for transition zone pull-through (≤5 cm 3%, >5 cm 0%, P = 0.112). EPM ≤5 cm had more frequent involuntary daytime bowel movements (P = 0.041) and more frequent voluntary bowel movements (P = 0.035). There were no differences in other measures of fecal incontinence severity. CONCLUSIONS: Shorter proximal extended margins beyond the adequate ganglionated margin do not significantly impact post-operative complication rates and have an unclear effect on fecal incontinence. TYPE OF STUDY: Case Control. LEVEL OF EVIDENCE: Level III.

Does Delayed Diagnosis of Hirschsprung Disease Impact Post-operative and Functional Outcomes? A Multi-Center Review From the Pediatric Colorectal and Pelvic Learning Consortium.

BACKGROUND: Hirschsprung Disease (HD) is a rare cause of functional bowel obstruction in children. Patients are typically diagnosed in the neonatal period and undergo pull-through (PT) soon after diagnosis. The optimal management and post-operative outcomes of children who present in a delayed fashion are unknown. METHODS: A multi-center retrospective review of children with HD was performed at participating Pediatric Colorectal and Pelvic Learning Consortium sites. Children were stratified by age at diagnosis (neonates <29 days; infants 29 days-12 months; toddler 1 year-5 years and child >5 years). RESULTS: 679 patients with HD from 14 sites were included; Most (69%) were diagnosed in the neonatal period. Age at diagnosis was not associated with differences in 30-day complication rates or need for PT revision. Older age at diagnosis was associated with a greater likelihood of undergoing fecal diversion after PT (neonate 10%, infant 12%, toddler 26%, child 28%, P < 0.001) and a greater need for intervention for constipation or incontinence postoperatively (neonate 56%, infant 62%, toddler 78%, child 69%, P < 0.001). CONCLUSION: Delayed diagnosis of HD does not impact 30-day post-operative outcomes or need for revision surgery but, delayed diagnosis is associated with increased need for fecal diversion after pull-through. LEVEL OF EVIDENCE: III.

Vascular endothelial growth factor receptor-2 inhibition in experimental murine colitis.

BACKGROUND: In the setting of inflammatory bowel disease, inflammation is associated with a simultaneous increase in angiogenesis; moreover, elevated vascular endothelial growth factor (VEGF) levels implicate angiogenesis as a pathologic contributor to disease severity. We hypothesize that selectively inhibiting vascular endothelial growth factor receptor-2 (VEGFR2) in a model of murine colitis will reduce angiogenesis, resulting in decreased inflammation and disease severity, providing mechanistic insight into the role of pathologic angiogenesis in IBD. MATERIALS AND METHODS: In a dextran sodium sulfate model of murine colitis, anti-VEGFR2 monoclonal antibody (DC101) or placebo was administered. Clinical assessments followed by histologic and molecular tissue analysis were performed to quantify inflammation, microvessel density (MVD), VEGF and VEGFR2 gene expression, and phosphorylated mitogen-activated protein kinase protein expression. RESULTS: Weight loss began after d 6 with the treatment group demonstrating a more favorable percent weight change. Inflammation and MVD were similar between cohorts, both increasing in parallel toward a plateau. VEGF and VEGFR2 messenger RNA expression were not significantly different, but phosphorylated mitogen-activated protein kinase was elevated in the DC101 cohort (P = 0.03). CONCLUSIONS: Despite a more favorable weight change profile in the treated group, no difference was observed between cohorts regarding clinical disease severity. However, a parallel rise in inflammation and MVD was observed coinciding with weight loss, suggesting their relationship in IBD. VEGFR2 downstream signaling was significantly elevated in the treated cohort, possibly by VEGF-independent signal transduction. Early and effective inhibition of angiogenesis by limiting downstream VEGF signaling or targeting multiple angiogenic pathways may block angiogenesis, thereby reducing disease severity and provide evidence toward the mechanism and clinical benefit of antiangiogenics in the setting of IBD.

Pyloric atresia with epidermolysis bullosa: fetal MRI diagnosis with postnatal correlation.

Pyloric atresia is an uncommon congenital gastric outlet obstruction, accounting for only 1% of gastrointestinal atresias. Up to 55% of cases have associated anomalies, the most common of which is epidermolysis bullosa. Fetal MRI findings of the epidermolysis bullosa-pyloric atresia association have not been previously reported. We present a case of this association diagnosed by prenatal MRI with corroborative postnatal imaging and surgical findings.

Long-Term Male Sexual Function and Fecal Incontinence Outcomes for Adult Patients with Hirschsprung Disease or Anorectal Malformation.

BACKGROUND: This study sought to characterize sexual function and fecal incontinence related quality of life (QOL) outcomes for adult males with anorectal malformation (ARM) or Hirschsprung's Disease (HD). METHODS: We conducted a cross-sectional survey study of male patients ≥18 years with ARM or HD. Patients were identified from our institutional database, contacted and consented by telephone, and sent a REDCap survey via email. The International Index of Erectile Function (IIEF-5) and Male Sexual Health Questionnaire (MSHQ) evaluated erectile dysfunction (ED) and ejaculatory dysfunction (EjD), respectively. The Cleveland Clinic Incontinence Score (CCIS) and the Fecal Incontinence Quality of Life Scale (FIQLS) assessed fecal incontinence-related outcomes. A linear regression analysis of IIEF-5 scores compared to CCIS scores was used to evaluate for an association between ED and incontinence. RESULTS: Of 63 patients contacted, 48 completed the survey. The median age for respondents was 22.5 years (IQR 20-25). There were 19 patients with HD and 29 patients with ARM. On the IIEF-5 survey, 35.3% report some level of ED. On the MSHQ-EjD survey, the median score was 14 out of 15 (IQR 10.75-15), indicating few EjD concerns. The median CCIS was 5 (IQR 2.25-7.75) and the median FIQL scores ranged from 2.7 to 3.5 depending on the domain assessed, demonstrating some QOL challenges secondary to fecal incontinence. On linear regression analysis, IIEF-5 and CCIS scores were weakly associated (B = -0.55, p = 0.045). CONCLUSIONS: Male adult patients with ARM or HD may have ongoing concerns with sexual function and fecal incontinence. LEVEL OF EVIDENCE: Level 4. TYPE OF STUDY: Cross-Sectional Survey Study.

Hirschsprung-Associated Enterocolitis at a Referral Institution: A Retrospective Review.

BACKGROUND: Hirschsprung-associated enterocolitis (HAEC) is the most common cause of morbidity and mortality amongst patients with Hirschsprung disease (HD); rectal Botulinum toxin (Botox) has been reported a possible prevention strategy. We aimed to evaluate our institution's historic cohort of HD patients, first to determine our incidence of HAEC and second to begin assessing the effect of Botox on HAEC incidence. METHODS: Patients with HD seen at our institution between 2005 and 2019 were reviewed. Incidence of HD and frequencies of HAEC and Botox injections were tallied. Associations between initial Botox treatment or transition zone and HAEC incidence were evaluated. RESULTS: We reviewed 221 patients; 200 were included for analysis. One hundred thirteen (56.5%) patients underwent primary pull-through at a median age of 24 days (IQR 91). Eighty-seven (43.5%) patients with initial ostomy had their intestinal continuity reestablished at a median of 318 days (IQR 595). Ninety-four (49.5%) experienced at least one episode of HAEC and 62 (66%) experienced multiple episodes of HAEC. Nineteen (9.6%) patients had total colonic HD and had an increased total incidence of HAEC compared to patients without total colonic HD (89% vs 44%, p < 0.001). Six (2.9%) patients received Botox injections at the time of pull-through or ostomy takedown; one experienced an episode of HAEC (versus 50.7% of the patients who were confirmed to have not received Botox injections at their surgery, p = 0.102). CONCLUSION: Further prospective study on Botox's effect on Hirschsprung-associated enterocolitis is required and is the next step in our investigation. LEVEL OF EVIDENCE: Level III.

Sacral Nerve Stimulation in Children with Medically Refractory Fecal Incontinence or Severe Constipation.

INTRODUCTION: The goal of this study was to evaluate outcomes in patients treated with sacral nerve stimulation (SNS) for medically refractory fecal incontinence or severe constipation. METHODS: We performed a retrospective cohort study of all patients treated with SNS after failed medical management at a single center between 9/1/2015 and 6/30/2022. Demographic and clinical data was extracted from the electronic medical record. Rates of involuntary bowel movements were evaluated using a bowel severity score questionnaire and compared pre- and post-SNS using McNemar and McNemar-Bowker tests. RESULTS: 70 patients underwent SNS placement. The median age was 12.8 years (IQR 8.6-16.0) and 61.4% were male. The most common diagnosis was idiopathic constipation (67.1%), followed by anorectal malformation (15.7%), and others. 43 patients had severity scores recorded both pre- and at least 90 days post-SNS insertion. The rates of daytime and nighttime involuntary bowel movements were significantly different pre-compared to post-SNS placement (p = 0.038 and p = 0.049, respectively). The rate of daytime and nighttime fecal continence increased from 44% to 58.1% and 53.5%-83.7%, respectively. The rate of at least weekly daytime and nighttime fecal incontinence decreased from 48.8% to 18.7% and 34.9%-7.0%, respectively. Minor pain/neurological symptoms occurred in 40% of patients, while 5.7% developed a wound infection. Further surgery for the SNS was required in 40% of patients. CONCLUSIONS: SNS placement can be an effective treatment for medically refractory fecal incontinence. Minor complications and the need for further procedures are common, while more serious complications like wound infections are rare. TYPE OF STUDY: Retrospective Cohort Study. LEVEL OF EVIDENCE: Level 3.

Rectal Prolapse Following Repair of Anorectal Malformation: Incidence, Risk Factors, and Management.

BACKGROUND: The incidence and optimal management of rectal prolapse following repair of an anorectal malformation (ARM) has not been well-defined. METHODS: A retrospective cohort study was performed utilizing data from the Pediatric Colorectal and Pelvic Learning Consortium registry. All children with a history of ARM repair were included. Our primary outcome was rectal prolapse. Secondary outcomes included operative management of prolapse and anoplasty stricture following operative management of prolapse. Univariate analyses were performed to identify patient factors associated with our primary and secondary outcomes. A multivariable logistic regression was developed to assess the association between laparoscopic ARM repair and rectal prolapse. RESULTS: A total of 1140 patients met inclusion criteria; 163 (14.3%) developed rectal prolapse. On univariate analysis, prolapse was significantly associated with male sex, sacral abnormalities, ARM type, ARM complexity, and laparoscopic ARM repairs (p < 0.001). ARM types with the highest rates of prolapse included rectourethral-prostatic fistula (29.2%), rectovesical/bladder neck fistula (28.8%), and cloaca (25.0%). Of those who developed prolapse, 110 (67.5%) underwent operative management. Anoplasty strictures developed in 27 (24.5%) patients after prolapse repair. After controlling for ARM type and hospital, laparoscopic ARM repair was not significantly associated with prolapse (adjusted odds ratio (95% CI): 1.50 (0.84, 2.66), p = 0.17). CONCLUSION: Rectal prolapse develops in a significant subset of patients following ARM repair. Risk factors for prolapse include male sex, complex ARM type, and sacral abnormalities. Further research investigating the indications for operative management of prolapse and operative techniques for prolapse repair are needed to define optimal treatment. TYPE OF STUDY: Retrospective cohort study. LEVEL OF EVIDENCE: II.

EGFR inhibition fails to suppress vascular proliferation and tumor growth in a Ewing's sarcoma model.

BACKGROUND: Expression of epidermal growth factor receptor (EGFR), a potent regulator of cellular homeostasis, is associated with aggressive tumor behavior. The mechanism by which EGFR inhibition functions is unclear, with controversial results demonstrating an effect on the tumor cells, endothelial cells, or pericytes. EGFR activation has been linked to the expression of vascular endothelial growth factor (VEGF), a known mitogen of angiogenesis, but the relationship between these factors and their effect on tumor vessel development is vague. We hypothesized that using an EGFR inhibitor on a human Ewing's sarcoma model would inhibit tumor growth by suppressing vessel proliferation. METHODS: A cell proliferation assay was performed on the Ewing's sarcoma (SK-NEP-1) cell line. Tumor cells were implanted intrarenally in athymic mice. Animals received daily gavage with vehicle or gefitinib 1 wk following implantation. Mice (n = 12/cohort) were euthanized 6 wk following implantation. Remaining mice were maintained without treatment for 2 wk. Vascular changes were assessed by angiography and immunohistochemically. EGFR and vascular endothelial growth factor (VEGF) expression were quantified using quantitative polymerase chain reaction (qPCR). RESULTS: Gefitinib suppressed in vitro cell growth with an IC(50) = 1.36 µM. Minimal tumor growth suppression was noted at 6 wk (6.01 ± 1.2 g in control versus 4.61 ± 0.9 g treated, P = 0.36). After cessation of gefitinib, tumor growth was increased in both groups (7.37 ± 1.62 g versus 6.77 ± 1.53 g, P = 0.79). Microvessel density was unchanged despite EGFR inhibition (161,000 ± 16,000 pixels versus 135,000 ± 18,000 pixels, P = 0.31). At 6 wk, the vascular maturity index was similar in both groups (3.63 ± 1.12 versus 4.09 ± 1.71, P = 0.83). A downward trend in EGFR expression (49% of control) and an upward trend in VEGF levels (50% of control) occurred in the treated group. CONCLUSIONS: EGFR expression was suppressed in cultured cells and xenograft tumors. Despite a cytotoxic effect on cell lines, gefitinib had little effect on tumor growth. No effects on the tumor vasculature were noted in the setting of EGFR suppression, suggesting that angiogenesis induced by SK-NEP-1 cells is refractory to EGFR inhibition. Interestingly, the resulting increase in VEGF expression following EGFR blockade, provides an alternative pro-angiogenic pathway promoting tumor survival.

Hospital and Professional Charges and Reimbursement Patterns in Pediatric Extracorporeal Membrane Oxygenation.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is an expensive therapeutic modality. We sought to identify the main charge contributors to patient bills and analyze their patterns of reimbursement. We additionally sought to evaluate the impact of 2015 Current Procedural Terminology (CPT) code changes in professional billing for pediatric surgeons. METHODS: A retrospective review of ECMO cases at a standalone quaternary children's hospital between 2008-2017 was performed. Itemized hospital and professional bills were analyzed. RESULTS: Top charges included room rates, nitric oxide, medications, invasive support and monitoring, and laboratory testing. Average reimbursement was ∼60% for hospital and ∼36% for professional bills. CPT code changes in 2015 represented a 65% reduction in RVUs and 46% reduction in professional charges. Medicaid reimbursement for professional billing remained stable at 9%, and commercial reimbursement fell from 70% to 59% during the study period. CONCLUSIONS: The main drivers of ECMO charges are unrelated to ECMO supplies or surgery. Evidence-based guidelines for ECMO management could make a difference in healthcare expenditure. Modern CPT codes depreciate RVUs and professional charges, compromising revenue. As the infrastructure required to provide this service is costly, diminishing returns may limit access to this therapy.

Surgical history of Hirschsprung disease.

Harald Hirschsprung presented the first comprehensive and detailed description of clinical outcomes in patients with congenital megacolon. In the century following his discovery, we have seen realization of the etiology, diagnosis, and treatment of Hirschsprung disease. In this article we describe the surgical management of Hirschsprung disease starting with Orvar Swenson, who pioneered the field with the first full thickness transrectal dissection followed by several additional innovative surgeons who have contributed to the modifications that have brought us to the modern surgical management of Hirschsprung Disease.

Hirschsprung's disease in low- and middle-income countries.

Hirschsprung's disease (HD) is one of the most common causes of pediatric bowel obstruction in low- and middle-income countries (LMICs). This paper describes the unique aspects of presentation, diagnosis, management and post-operative care and outcomes of HD in LMICs. In LMICs, patients with HD are much more likely to present in a delayed fashion with subsequent increased morbidity and mortality including higher rates of chronic obstruction, malnutrition with failure to thrive, complete obstruction and perforation. There are multifactorial causes for delay, with opportunities to improve initial timely diagnosis and referral, support families to address socioeconomic and cultural barriers, and improve workforce and infrastructure resources to provide definitive care. In LMICs, the diagnosis is often made based on clinical presentation and radiographic findings as pathological services may be limited. Initial diversion with multi-stage procedure, instead of a single-stage pull-through, predominates. This is also a result of multifactorial causes, including initial presentation to general surgeons at first-level hospitals instead of pediatric surgeons, delayed presentation with sick, malnourished children with significantly distended bowel, and a lack of fresh-frozen pathological services to guide the extent of resection. Post-operatively, HD patients in LMICs experience higher complication and mortality rates - likely stemming from sicker baseline presentations and more limited resources. Significant recent advances in care have occurred for patients with HD in LMICs, while opportunities to continue to improve care remain.

Prospective quality of life outcomes in pediatric fecal incontinence following bowel management.

BACKGROUND: Severe fecal incontinence (FI) is common in patients both with and without anorectal malformations. Whether a formal bowel management program (BMP) has significant effects on FI, psychosocial development of the child, and caregiver stress is poorly understood. We hypothesize that BMP participation results in long-term clinical and quality of life (QOL) improvements for patients and caregivers. METHODS: Using a prospective cohort study over three years, 342 children (age 3-12 years) and caregivers were followed for one year after attending a week-long BMP, during which a regimen was tailored to promote daily stool evacuation.FI QOL was measured with the validated Cincinnati Fecal Incontinence Scale (CINCY-FIS), evaluating multiple subscales, including parental stress. Scores were obtained at multiple timepoints following BMP (baseline, 2 weeks, 3 months, 1 year). RESULTS: Within 2 weeks, BMP participation significantly improved FI with increased frequency of daily daytime voluntary bowel movements (20%-70%, p < 0.001) and decreased daily daytime and nighttimeinvoluntary bowel movements (60%-20%, p < 0.001; 30%-10%, p < 0.05). Marked improvements in CINCY-FIS were observed across multiple QOL subscales, with the greatest in parental stress, and sustained through one year. CONCLUSIONS: BMP results in significant and sustained improvement in FI and QOL for patients and caregivers.