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Esophageal atresia with or without tracheoesophageal fistula and tracheobronchomalacia encompass 2 of the most common complex congenital intrathoracic anomalies. Tailoring interventions to address the constellation of problems present in each patient is essential. Due to advances in neonatology, anesthesia, pulmonary, gastroenterology, nutrition and surgery care for patients with complex congenital tracheoesophageal disorders has improved dramatically. Treatment strategies tailored to the individual patient needs are best implimented under the aegis of a comprehensive longitudinal multidisciplinary care team.

The “rule of 3” is a 40-year-old expert opinion that suggests dilating an esophageal stricture more than 3?mm is unsafe. Few studies have evaluated this tenet, and do not specify how much larger than 3?mm is reasonable. Our aim was to determine the optimal point for maximum dilation diameter with acceptable risk in a pediatric population. A retrospective review in pediatric patients with esophageal strictures was performed. The number of millimeters the stricture was dilated, defined as delta dilation diameter (?DD), was determined by subtracting the initial stricture diameter from the diameter of the largest balloon used. Receiver operating characteristic curve analysis was used to evaluate the discriminatory ability of ?DD. Youden Jindex was used to identify optimal cut-point in predicting perforation. Two hundred eighty-four patients underwent 1384 balloon dilations. Overall perforation rate was 1.66%. There were 8 perforations in 1075 dilations with ?DD =5?mm (0.7%) and 15 perforations in 309 dilations with ?DD >5?mm (4.9%). Youden Jindex found an optimal cutoff to be at a ?DD of =5?mm. The cumulative rate of perforation for all dilations =5?mm was 0.74% whereas the cumulative risk of perforation for all dilations =6?mm was 4.85% (P?

The role of intralesional steroid injection (ISI) in the treatment of anastomotic stricture in patients with esophageal atresia remains unclear. The aim of this study was to evaluate the efficacy and safety of ISI. A total of 158 patients with esophageal atresia with at least 1 ISI for the treatment of esophageal anastomotic stricture between 2010 and 2017 were identified. The change in stricture diameter (?D) was compared between procedures with dilation alone (ISI-) and dilation with steroid injection (ISI+). A total of 1055 balloon dilations were performed (452 ISI+). The median ?D was significantly greater in the ISI+ group: 1 mm (interquartile range [IQR] 0, 3) versus 0 mm (IQR -1, 1.5) (P< 0.0001). The ISI+ group had greater percentage of improved diameter (P< 0.0001) and lesser percentages of unchanged and decreased diameters at subsequent endoscopy (P= 0.0009, P= 0.003). Multivariable logistic regression confirmed the significance of ISI on increasing the likelihood of improved stricture diameter with an adjusted odds ratio of 3.24 (95% confidence interval: 2.15–4.88) (P< 0.001). The ?D for the first 3 ISI+ procedures was greater than the ?D for subsequent ISI+ procedures: 1 mm (IQR 0, 3) versus 0.5 mm (IQR-1.25, 2) (P= 0.001). There was no difference in perforation incidence between ISI+ and ISI- groups (P= 0.82). ISI with dilation was well tolerated and improved anastomotic stricture diameter more than dilation alone. The benefit of ISI over dilation alone was limited to the first 3 ISI procedures.

Esophagitis is highly prevalent in patients with esophageal atresia (EA). Peptic esophagitis has long been assumed to be the primary cause of esophagitis in this population, and prolonged acid suppressive medication usage is common; such treatment is of unknown benefit and carries potential risk. To better understand the role of commonly used antireflux treatments in EA, we analyzed all patients with repaired EA who underwent endoscopy with biopsies at our institution between January 2016 and August 2018. Macroscopic erosive and histologic esophagitis on biopsy was graded per predefined criteria. Clinical characteristics including acid suppressive medication usage, type of EA and repair, presence of hiatal hernia, and history of fundoplication were reviewed. There were 310 unique patients (33.5% long gap EA) who underwent 576 endoscopies with biopsies during the study period. Median age at endoscopy was 3.7 years (interquartile range 21–78 months). Erosive esophagitis was found in 8.7% of patients (6.1% of endoscopies); any degree of histologic eosinophilia (=1 eosinophil/high power field [HPF]) was seen in 56.8% of patients (48.8% of endoscopies), with >15 eosinophils/HPF seen in 15.2% of patients (12.3% of endoscopies). Acid suppression was common; 86.9% of endoscopies were preceded by acid suppressive medication use. Fundoplication had been performed in 78 patients (25.2%). Proton pump inhibitor (PPI) and/or H2 receptor antagonist (H2RA) use were the only significant predictors of reduced odds for abnormal esophageal biopsy (P= 0.011 for PPI, P= 0.048 for H2RA, and P= 0.001 for PPI combined with H2RA therapy). However, change in intensity of acid suppressive therapy by either dosage or frequency was not significantly associated with change in macroscopic erosive or histologic esophagitis (P> 0.437 and P> 0.13, respectively). Presence or integrity of a fundoplication was not significantly associated with esophagitis (P= 0.236). In EA patients, acid suppressive medication therapy is associated with reduced odds of abnormal esophageal biopsy, though histologic esophagitis is highly prevalent even with high rates of acid suppressive medication use. Esophagitis is likely multifactorial in EA patients, with peptic esophagitis as only one of multiple possible etiologies for esophageal inflammation. The clinical significance of histologic eosinophilia in this population warrants further investigation.

Esophageal perforation is a potentially life-threatening problem if not quickly diagnosed and treated appropriately. Negative-pressure wound therapy, commercially known as V.A.C. therapy, was developed in the early 1990s and is now standard of care for chronic surface wounds, ulcers, and burns. Adapting vacuum sponge therapy for use intraluminally for perforations of the esophagus was first reported in 2008. We report the first pediatric experience on a customized esophageal vacuum–assisted closure (EVAC) device for closure of esophageal perforations. To evaluate the technical feasibility, safety, and efficacy of EVAC in a pediatric population with esophageal perforations and compare efficacy to a cohort of patients who underwent stenting for esophageal perforation. We performed an institutional review board–approved retrospective chart review on all patients who underwent EVAC for esophageal perforations (October 2013–September 2017) and who underwent externally removable stent placement for esophageal perforation (January 2010–December 2017) at our institution. Our primary aim was to evaluate technical feasibility, efficacy, and safety in the treatment of pediatric esophageal perforations. A secondary aim was to compare the efficacy of EVAC to esophageal stenting in healing esophageal perforations in our pediatric population. A total of 17 patients with esophageal atresia underwent therapy for esophageal perforation. Eight sponges were placed for surgical perforation and 9 were placed after endoscopic therapy perforation. The median age of patients was 24 months with the youngest patient being 3 months of age. The success rate of EVAC to seal all esophageal perforations was 88% (15/17). The success rate was similar in both subgroups: surgical anastomotic leaks at 88% (7/8) and endoscopic therapy leaks at 89% (8/9). There were no technical failures with placement. The stent group had a total of 24 patients: 19 were placed secondary to perforations from endoscopic therapy and 5 were placed secondary to surgical anastomotic perforations. The success rate of stents to seal all esophageal perforations was 63% (15/24). The success rate in the subgroups was 74% (14/19) for endoscopic therapy leaks and 20% (1/5) for surgical anastomotic leaks. In comparing success of EVAC and stent therapy, we found a statistically significant difference in favor of EVAC in healing surgical anastomotic perforations (P= 0.032). There was, however, no statistical difference in healing endoscopic therapy perforations (P= 0.360). EVAC is a novel, promising technique for the treatment of esophageal perforations in a pediatric population. This treatment is comparable to esophageal stenting in iatrogenic endoscopic therapy perforations and superior to stenting surgical perforations. Further prospective studies are needed to compare the effectiveness of EVAC to esophageal stenting. Improvement in device design and customization could further improve success and ease of placement.

Refractory esophageal strictures are rare conditions in pediatrics, and are often due to anastomotic, congenital, or caustic strictures. Traditional treatment options include serial dilation and surgical stricture resection; endoscopic intralesional steroid injections, mitomycin C, and externally removable stents combined with dilation have had variable success rates. Although not as widely used, endoscopic electrocautery incisional therapy (EIT) has been reported as an alternative treatment for refractory strictures in a small number of adult series. The aim of the study was to evaluate the safety and efficacy of EIT in a pediatric population with refractory esophageal strictures. A retrospective chart review was conducted on all patients who underwent EIT for esophageal strictures (May 2011–September 2017) at our tertiary-care referral center. A total of 57 patients underwent EIT. Procedural success was defined as no stricture resection, appropriate diameter for age, and fewer than 7 dilations within 24 months of first EIT session. This corresponded to the 90th percentile of the observed number of dilations in the data. All patients included in the study had at least 2-year follow-up. A total of 133 EIT sessions on 58 distinct anastomotic strictures were performed on 57 patients (24 girls). The youngest patient to have EIT was 3 months old and 4.8 kg. There were 36 strictures that met the criteria for refractory stricture and 22 non-refractory (NR) strictures. The median number of dilations before EIT therapy was 8 (interquartile range [IQR]: 6–10) in the refractory group and 3 (IQR: 0–3) in the NR group. In the refractory group, 61% of the patients met the criteria for treatment success. The median number of dilations within 2 years of EIT in the refractory group was 2 (IQR: 0–4). In the NR group, 100% of the patients met criteria for success. The median number of dilations within 2 years of EIT in the NR was 1 (IQR: 0–2). The overall adverse event rate was 5.3% (7/133), with 3 major (2.3%) and 4 minor events (3%). EIT shows promise as an adjunct treatment option for pediatric refractory esophageal strictures and may be considered before surgical resection even in severe cases. The complication rate, albeit low, is significant, and EIT should only be considered by experienced endoscopists in close consultation with surgery. Further prospective longitudinal studies are needed to validate this treatment.

Gastro-jejunostomy tubes (GJT) are commonly used for enteral nutrition in patients with gastric feeding intolerance, gastroesophageal reflux, and those at high risk of aspiration. Complications are generally minor, however highly morbid complications exist, specifically in younger and smaller infants.

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This article conveys early findings with respect to changes in patient and graft survival since Centers for Medicare & Medicaid Services (CMS) regulations for Medicare coverage of solid organ transplantation became effective on 28 June 2007.

Approximately 740,000 Ci of 131I were released into the atmosphere from the Hanford Nuclear Site in Washington State during 1944–1957. The Hanford Thyroid Disease Study (HTDS), conducted to determine if thyroid disease is increased among persons exposed as children to that 131I, also investigated whether thyroid ultrasound (US) abnormalities might be increased. The HTDS cohort (n= 5199) was selected from 1940–1946 births to mothers with usual residence in seven Washington counties. Of these, 4350 were located alive, 3447 attended HTDS clinics (1992–1997), and 3440 (1747 females) had evaluable clinical results and sufficient data to characterize their Hanford 131I exposures. US abnormalities were observed in 55.5% of women and 37.4% of men. Thyroid radiation doses from Hanford 131I, which could be estimated for 3191 evaluable participants, ranged from 0.0029 to 2823 mGy (mean, 174 mGy). Estimated dose was not significantly associated with the prevalence of any US abnormality (p= 0.21), US nodules with maximum dimension 5 mm or more (p= 0.64), or average number of US nodules per person (p= 0.80 for nodules with maximum dimension 5 mm or more). These results remained unchanged after accounting for factors that might confound or modify dose-response relationships and for uncertainty of the dose estimates. This study does not support the hypothesis that 131I exposure at Hanford's dose levels and dose rates during infancy and childhood increases the prevalence of adult thyroid US abnormalities.

Gene transfer technology may provide a novel approach to treatment for pancreatic diseases. Recombinant adenovirus achieves efficient gene transfer in vivo. In this study, a murine model of adenoviral-mediated pancreatic gene transfer was developed, and the factors responsible for adenoviral elimination were investigated. Three days after direct pancreatic injection of a replication-defective adenovirus containing the lacZtransgene, a high proportion (76.8 ± 6.7) of pancreatic cells expressed β-galactosidase, the gene product. Gene expression was absent by 28 days posttransduction. In immunodeficient mice, β-galactosidase expression persisted with 20.0 ± 6.0 of pancreatic cells staining positive 60 days after viral transduction. To test whether early viral proteins are the antigenic components responsible for the potent antiviral immune response, normal mice were injected with different adenoviral vectors containing early gene deletions. Vectors containing deletions in early region 2 or 4 expressed β-galactosidase at 28 days. Presently available adenoviral vectors engineered to avoid this response offer minimal improvements in transgene duration. Further vector modifications or alternative strategies are needed to achieve stable pancreatic adenoviral transgene expression.

We studied the risk of thyroid neoplasia in Marshall Islanders exposed to radioiodines in nuclear fallout from the 1954 BRAVO thermonuclear test. We screened 7266 Marshall Islanders for thyroid nodules; the islanders were from 14 atolls, including several southern atolls, which were the source of the best available unexposed comparison group. Using a retrospective cohort design, we determined the prevalence of thyroid nodularity in a subgroup of 2273 persons who were alive in 1954 and who therefore were potentially exposed to fallout from the BRAVO test. For those 12 atolls previously thought to be unexposed to fallout, the prevalence of thyroid nodules ranged from 0.9% to 10.6%. Using the distance of each atoll from the test site as a proxy for the radiation dose to the thyroid gland, a weighted linear regression showed an inverse linear relationship between distance and the age-adjusted prevalence of thyroid nodules. Distance was the strongest single predictor in logistic regression analysis. A new absolute risk estimate was calculated to be 1100 excess cases/Gy/y/1 × 106 persons (11.0 excess cases/rad/y/1 million persons), 33% higher than previous estimates. We conclude that an excess of thyroid nodules was not limited only to the two northern atolls but extended throughout the northern atolls; this suggests a linear dose-response relationship.(JAMA 1987;258:629-636)

Triton X-100 treatment or freeze-thawing damages the membranes of sporulating or vegetative cells as seen by protein leakage from cells. A 40% increase in the specific [14C]benzylpenicillin-binding capacity of detergent-treated or frozen sporulating cells was observed. Neither freezing nor Triton X-100 treatment of vegetative cells produced a detectable effect on their [14C]benzylpenicillin-binding capacity. These data indicate the presence of penicillin-binding sites in intact sporulating bacilli not accessible to penicillin in routine binding assays. The chemical specificity of [14C]benzylpenicillin binding to detergent-treated sporulating cells is similar to that observed with untreated vegetative or sporulating cells.

ABSTRACTPancreatic adenoviral gene transfer can be achieved with high efficiency; however, questions concerning tissue injury from this commonly used vector have not been addressed. In these experiments, the effects of adenoviral gene transfer on pancreatic exocrine function were evaluated. Direct pancreatic injection with an adenoviral vector containing the Escherichia coliββ-galactosidase (ββ-Gal; lacZ) transgene (H5.010CBlacZ) resulted in a high level of transgene expression (64 ±± 6% of pancreatic cells expressed ββ-Gal) at 3 days following infection. However, amylase levels in four of five different subcellular pancreatic fractions were significantly decreased at this time point. Direct pancreatic injection with either saline or psoralen/UV-inactivated adenovirus did not have this effect, whereas both transduction with an adenoviral vector containing a different transgene and transduction with a homologous transgene resulted in decreased pancreatic amylase. The decrease in subcellular amylase levels persisted at 7 days post-transduction, and then returned to baseline at 21 days post-transduction. There was associated histologic damage (increased edema, inflammation, cell destruction, and vacuolization) at 3 and 7 days post-transduction, which resolved by 21 days. In summary, adenoviral transduction of the pancreas results in increased viral transgene expression and a uniform decrease in host amylase production throughout the pancreas. The normalization of amylase levels and histology suggest that organ recovery occurs. Gene transfer technology as a novel strategy for pancreatic diseases such as diabetes, pancreatitis, and cystic fibrosis is feasible but will benefit from continued approaches to limit toxicity.