Genomic Contributors to Esophageal Atresia and Tracheoesophageal Fistula: A 12 Year Retrospective Review.

OBJECTIVE: To evaluate genetic testing utilization and diagnostic yield in infants with esophageal atresia (EA)/tracheoesophageal fistula (TEF) over the past 12 years to inform future practices and individualize prognostication and management. STUDY DESIGN: A retrospective cohort study was performed for all infants with EA or EA/TEF hospitalized between January 2011 and January 2023 at a quaternary children's hospital. For each infant, demographic information, prenatal and postnatal history, and genetic testing were reviewed. RESULTS: There were 212 infants who were classified as follows: 1) complex/syndromic with EA/TEF plus an additional major anatomic anomaly (n = 114, of which 74 met VACTERL criteria); 2) isolated/nonsyndromic EA/TEF (n = 88) and 3) isolated/nonsyndromic EA (n = 10). A range of genetic tests were sent with varying diagnostic rates including karyotype analysis in 12 (all with complex/syndromic phenotypes and all positive), chromosomal microarray analysis in 189 (114 of whom were complex/syndromic with an overall diagnostic rate of 3/189), single gene testing for CHD7 in 18 (4 positive), and exome analysis in 37 complex/syndromic patients (8 positive). CONCLUSIONS: EA/TEF with and without additional anomalies is genetically heterogeneous with a broad range of associated phenotypes. While the genetic etiology of EA/TEF with or without VACTERL remains largely unknown, genome wide testing (exome or genome) including copy number analysis is recommended over chromosomal microarray testing. We anticipate that expanded genetic/genomic testing modalities such as RNA sequencing and tissue specific molecular testing are needed in this cohort to improve our understanding of the genomic contributors to EA/TEF.

Esophageal Dilation in Children: A State of the Art Review.

Esophageal dilations in children are performed by several pediatric and adult professionals. We aim to summarize improvements in safety and new technology used for the treatment of complex and refractory strictures, including triamcinolone injection, endoscopic electro-incisional therapy, topical mitomycin-C application, stent placement, functional lumen imaging probe assisted dilation, and endoscopic vacuum-assisted closure in the pediatric population.

Measurement of Stricture Dimensions Using a Visual Comparative Estimation Method With Biopsy Forceps During Endoscopy.

BACKGROUND: Estimation of the dimensions of endoscopic findings such as stricture diameter is largely subjective. Accurate assessment of stricture dimensions has multiple benefits including facilitating the choice of appropriately sized endoscopic therapies for treating stricture, properly tracking response to endoscopic therapies between procedures, and potentially even predicting outcomes of endoscopic therapy. METHODS: Endoscopies performed in children with repaired esophageal atresia between August 2019 and August 2021 for which both (1) an endoscopic estimate of esophageal stricture diameter obtained by visual comparison with the known dimensions of the biopsy forceps and (2) an intraoperative esophageal fluoroscopy study were performed were included for analysis. Fluoroscopic stricture diameter measurements were manually obtained using a software ruler tool calibrated to the known dimensions of the intraluminal endoscope. Statistical concordance was calculated between the visual diameter estimates and the standard fluoroscopic stricture measurements. RESULTS: One hundred ninety-one endoscopies were included for analysis. Lin's concordance correlation coefficient was 0.92 (95% confidence interval: 0.89-0.94) between the visual diameter estimates and the fluoroscopic stricture measurements. Correlation was strongest for smaller to mid-sized stricture diameters. CONCLUSIONS: Use of the biopsy forceps as a visual reference of known dimensions enables accurate visual estimation of esophageal stricture diameter during endoscopy using commonly available tools, with high concordance with standard fluoroscopic measurement techniques.

Endoscopic management of esophageal mucosal bridges in children with esophageal atresia.

BACKGROUND AND STUDY AIMS: Esophageal mucosal bridge (EMB) may be diagnosed at the anastomotic site in children operated on for esophageal atresia (EA) but so far only a few cases (n = 4) have been reported. This study aimed to characterize EMB in children with EA, risk factors, and treatment. PATIENTS AND METHODS: This retrospective multicenter study recorded patient's characteristics, EMB diagnosis circumstances, endoscopic management, follow-up, and EMB recurrence in children with EA aged less than 18 years, compared with paired EA patients without EMB. RESULTS: Thirty patients were included (60% male, 90% EA/tracheoesophageal fistula, 43% associated malformations). Compared to 44 paired controls, EMB was associated with a history of nasogastric tube feeding (31% vs. 9.1%, p = 0.02) and severe gastroesophageal reflux disease (history of fundoplication: 41.4% vs. 13.6%, p < 0.01). 77% had symptoms (food impaction and/or dysphagia). Endoscopic management was performed in 53% of patients (83% electrocoagulation) with no technical difficulties or complications. 80% of the symptomatic patients with EMB improved after endoscopic treatment, independently of anastomotic stricture dilatation or not. CONCLUSION: EMB endoscopic management by electrocoagulation is safe and often leads to symptom improvement.

Predictors of enteral tube dependence in pediatric esophageal atresia.

Children with esophageal atresia (EA) may require enteral tube feedings in infancy and a subset experience ongoing feeding difficulties and enteral tube dependence. Predictors of enteral tube dependence have never been systematically explored in this population. We hypothesized that enteral tube dependence is multifactorial in nature, with likely important contributions from anastomotic stricture. Cross-sectional clinical, feeding, and endoscopic data were extracted from a prospectively collected database of endoscopies performed in EA patients between August 2019 and August 2021 at an international referral center for EA management. Clinical factors known or hypothesized to contribute to esophageal dysphagia, oropharyngeal dysphagia, or other difficulties in meeting caloric needs were incorporated into regression models for statistical analysis. Significant predictors of enteral tube dependence were statistically identified. Three-hundred thirty children with EA were eligible for analysis. Ninety-seven were dependent on enteral tube feeds. Younger age, lower weight Z scores, long gap atresia, neurodevelopmental risk factor(s), significant cardiac disease, vocal fold movement impairment, and smaller esophageal anastomotic diameter were significantly associated with enteral tube dependence in univariate analyses; only weight Z scores, vocal fold movement impairment, and anastomotic diameter retained significance in a multivariable logistic regression model. In the current study, anastomotic stricture is the only potentially modifiable significant predictor of enteral tube dependence that is identified.

Predictors and Outcomes of Fully Covered Stent Treatment for Anastomotic Esophageal Strictures in Esophageal Atresia.

BACKGROUND AND AIMS: Anastomotic strictures following surgical repair is one of the most common complications in esophageal atresia (EA). The utility of esophageal stenting to treat anastomotic esophageal strictures in pediatrics is unclear. Our primary aim was to evaluate whether esophageal stenting, in conjunction with dilation and other endoscopic therapies, prevented surgical stricture resection (SR). Our secondary aims were to evaluate predictors of successful esophageal stenting and evaluate adverse events from stent placement. METHODS: A retrospective review of pediatric patients with EA complicated by esophageal strictures was performed. The change in stricture diameter in millimeters from the time of stent removal to subsequent endoscopy was defined as delta diameter (ΔD). A receiver operating characteristic (ROC) curve analysis was performed to determine the discriminatory ability of ΔD. Youden J index was used to identify optimal cutoff-point in predicting stent success. A univariate and multivariate analysis were done to assess predictors of success. RESULT: Forty-nine esophageal anastomoses were stented to treat esophageal strictures. Stents prevented SR in 41% of patients. ROC curve analysis utilizing Youden J index identified ΔD of ≤4 mm (area under the curve = 0.790; 95% confidence interval: 0.655-0.924; P < 0.001) as the optimal cutoff point in differentiating stent success. The most common adverse events were erosions/ulcerations, granulation tissue formation, and vomiting/retching. CONCLUSION: Stent therapy in preventing SR at the site of EA repair was successful in 41% in our population with good long term follow-up. The most significant predictor of success in this study was the change in luminal diameter (≤4 mm) at initial poststent follow-up.

Comparison of Detection Methods for Tracheoesophageal Fistulae With a Novel Method: Capnography With CO2 Insufflation.

BACKGROUND: Tracheoesophageal fistulae (TEF) are difficult to detect and require a high index of suspicion. We hypothesized that capnography to identify a spike in end-tidal carbon dioxide (etCO2) during esophagoscopy with carbon dioxide (CO2) insufflation would facilitate TEF diagnosis because of gas passage from the esophagus to the trachea. METHODS: Medical records of 42 consecutive cases of recurrent, acquired, or missed congenital TEF diagnosed between January 2015 and November 2019 that underwent esophagoscopy with CO2 insufflation were reviewed. A control cohort of 97 similarly endoscopically evaluated patients with surgical confirmation of absence of recurrent TEF (eg, patients undergoing posterior tracheopexy) was also collected. All patients underwent pre-operative esophagoscopy, bronchoscopy, and capnography; diagnostic abilities of various combinations of modalities for TEF identification were calculated. RESULTS: Statistical analysis identified a maximum intra-esophagoscopy end-tidal CO2 level of 68 mmHg as the optimal discriminator between cases and controls, though in practice, we anecdotally find that recurrent TEFs typically permit rapid rise ≥90 mmHg. Increasing numbers of diagnostic modalities increased diagnostic sensitivity to detect recurrent TEF; the highest diagnostic sensitivity for TEF identification was achieved by the combination of intra-esophagoscopy fluoroscopy with bronchoscopy and capnography ≥68 mmHg (sensitivity = 88.1%). There were multiple cases of TEF (N = 7 for etCO2 ≥68 mmHg, N = 3 for etCO2 ≥90 mmHg) identified by capnography that were missed by esophagoscopy. There were 5 (for etCO2 ≥68 mmHg) or 6 (for etCO2 ≥90 mmHg) cases of recurrent TEF that were missed by all nonsurgical methods. CONCLUSION: Attention to etCO2 during esophagoscopy with CO2 insufflation represents a simple, novel way to detect TEF. Identification of TEF remains challenging, though combinations of diagnostic modalities improve diagnostic sensitivity.

Rules Are Meant to Be Broken: Examining the "Rule of 3" for Esophageal Dilations in Pediatric Stricture Patients.

BACKGROUND AND AIMS: 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. METHODS: A retrospective review in pediatric patients with esophageal strictures was performed. The number of millimeters the stricture was dilated, defined as delta dilation diameter (ΔDD), 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 ΔDD. Youden J index was used to identify optimal cut-point in predicting perforation. RESULTS: Two hundred eighty-four patients underwent 1384 balloon dilations. Overall perforation rate was 1.66%. There were 8 perforations in 1075 dilations with ΔDD ≤5 mm (0.7%) and 15 perforations in 309 dilations with ΔDD >5 mm (4.9%). Youden J index found an optimal cutoff to be at a ΔDD 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 < 0.001). CONCLUSIONS: Balloon dilations that expand the initial esophageal anastomosis ≤5 mm in a pediatric population appear to not unduly increase the risk of perforation. Further prospective studies are needed to further investigate the potential for a new rule of 5 for balloon dilation.

Intralesional Steroid Injection Therapy for Esophageal Anastomotic Stricture Following Esophageal Atresia Repair.

OBJECTIVES: 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. METHODS: 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 (ΔD) was compared between procedures with dilation alone (ISI-) and dilation with steroid injection (ISI+). RESULTS: A total of 1055 balloon dilations were performed (452 ISI+). The median ΔD 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 ΔD for the first 3 ISI+ procedures was greater than the ΔD 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). CONCLUSIONS: 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.

Utility of repeated therapeutic endoscopies for pediatric esophageal anastomotic strictures.

Anastomotic stricture is a common complication of esophageal atresia (EA) repair. Such strictures are managed with dilation or other therapeutic endoscopic techniques such as steroid injections, stenting, or endoscopic incisional therapy (EIT). In situations where endoscopic therapy is unsuccessful, patients with refractory strictures may require surgical stricture resection; however, the point at which endoscopic therapy should be abandoned in favor of repeat thoracotomy is unclear. We hypothesized that increasing numbers of therapeutic endoscopies are associated with increased likelihood of stricture resection. We retrospectively reviewed the records of patients with EA who had an initial surgery at our institution resulting in an esophago-esophageal anastomosis between August 2005 and May 2019. Up to 2 years of post-surgery endoscopy data were collected, including exposure to balloon dilation, intralesional steroid injection, stenting, and EIT. Primary outcome was need for stricture resection. Receiver operating characteristic (ROC) curve analysis and univariate and multivariable Cox proportional hazards regression analyses were performed. There were 171 patients who met inclusion criteria. The number of therapeutic endoscopies was a moderate predictor of stricture resection by ROC curve analysis (AUC = 0.720, 95% CI 0.617-0.823). With increasing number of therapeutic endoscopies, the probability of remaining free from stricture resection decreased. By Youden's J index, a cutoff of ≥7 therapeutic endoscopies was optimal for discriminating between patients who had versus did not have stricture resection, though an absolute majority of patients (≥50%) remained free of stricture resection at each number of therapeutic endoscopies through 12 endoscopies. Significant predictors of needing stricture resection by univariate regression included ≥7 therapeutic endoscopies, Foker surgery for long-gap EA, fundoplication, history of esophageal leak, and length of stricture ≥10 mm. Multivariate analysis identified only history of leak as statistically significant, though this regression was underpowered. The utility of repeated therapeutic endoscopies may diminish with increasing numbers of endoscopic therapeutic attempts, with a cutoff of ≥7 endoscopies identified by our single-center experience as our statistically optimal discriminator between having stricture resection versus not; however, a majority of patients remained free of stricture resection well beyond 7 therapeutic endoscopies. Though retrospective, this study supports that repeated therapeutic endoscopies may have clinical utility in sparing surgical stricture resection. Esophageal leak is identified as a significant predictor of needing subsequent stricture resection. Prospective study is needed.

Esophagitis in Pediatric Esophageal Atresia: Acid May Not Always Be the Issue.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Endoscopic Esophageal Vacuum Therapy: A Novel Therapy for Esophageal Perforations in Pediatric Patients.

BACKGROUND: 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. AIM: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Endoscopic Electrocautery Incisional Therapy as a Treatment for Refractory Benign Pediatric Esophageal Strictures.

BACKGROUND AND AIM: 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. METHODS: 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. RESULTS: 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%). CONCLUSIONS: 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.

ASGE Technology Committee systematic review and meta-analysis assessing the ASGE Preservation and Incorporation of Valuable Endoscopic Innovations thresholds for adopting real-time imaging-assisted endoscopic targeted biopsy during endoscopic surveillance of Barrett's esophagus.

BACKGROUND AND AIMS: Endoscopic real-time imaging of Barrett's esophagus (BE) with advanced imaging technologies enables targeted biopsies and may eliminate the need for random biopsies to detect dysplasia during endoscopic surveillance of BE. This systematic review and meta-analysis was performed by the American Society for Gastrointestinal Endoscopy (ASGE) Technology Committee to specifically assess whether acceptable performance thresholds outlined by the ASGE Preservation and Incorporation of Valuable Endoscopic Innovations (PIVI) document for clinical adoption of these technologies have been met. METHODS: We conducted meta-analyses calculating the pooled sensitivity, negative predictive value (NPV), and specificity for chromoendoscopy by using acetic acid and methylene blue, electronic chromoendoscopy by using narrow-band imaging, and confocal laser endomicroscopy (CLE) for the detection of dysplasia. Random effects meta-analysis models were used. Statistical heterogeneity was evaluated by means of I(2) statistics. RESULTS: The pooled sensitivity, NPV, and specificity for acetic acid chromoendoscopy were 96.6% (95% confidence interval [CI], 95-98), 98.3% (95% CI, 94.8-99.4), and 84.6% (95% CI, 68.5-93.2), respectively. The pooled sensitivity, NPV, and specificity for electronic chromoendoscopy by using narrow-band imaging were 94.2% (95% CI, 82.6-98.2), 97.5% (95% CI, 95.1-98.7), and 94.4% (95% CI, 80.5-98.6), respectively. The pooled sensitivity, NPV, and specificity for endoscope-based CLE were 90.4% (95% CI, 71.9-97.2), 98.3% (95% CI, 94.2-99.5), and 92.7% (95% CI, 87-96), respectively. CONCLUSIONS: Our meta-analysis indicates that targeted biopsies with acetic acid chromoendoscopy, electronic chromoendoscopy by using narrow-band imaging, and endoscope-based CLE meet the thresholds set by the ASGE PIVI, at least when performed by endoscopists with expertise in advanced imaging techniques. The ASGE Technology Committee therefore endorses using these advanced imaging modalities to guide targeted biopsies for the detection of dysplasia during surveillance of patients with previously nondysplastic BE, thereby replacing the currently used random biopsy protocols.

Enteroscopy.

Noninvasive imaging with CT and magnetic resonance enterography or direct visualization with wireless capsule endoscopy can provide valuable diagnostic information and direct therapy. Enteroscopy technology and techniques have evolved significantly and allow diagnosis and therapy deep within the small bowel, previously attainable only with intraoperative enteroscopy. Push enteroscopy, readily available in most endoscopy units, plays an important role in the evaluation and management of lesions located up to the proximal jejunum. Currently available device-assisted enteroscopy systems, DBE, SBE, and spiral enteroscopy each have their technical nuances, clinical advantages, and limitations. Newer, on-demand enteroscopy systems appear promising, but further studies are needed. Despite slight differences in parameters such as procedural times, depths of insertion, and rates of complete enteroscopy, the overall clinical outcomes with all overtube-assisted systems appear to be similar. Endoscopists should therefore master the enteroscopy technology based on institutional availability and their level of technical expertise.

Electronic chromoendoscopy.

Electronic chromoendoscopy technologies provide image enhancement and may improve the diagnosis of mucosal lesions. Although strides have been made in standardization of image characterization, especially with NBI, further image-to-pathology correlation and validation are required. There is promise for the development of a resect and discard policy for diminutive adenomas by using electronic chromoendoscopy; however, before this can be adopted, further community-based studies are needed. Further validated training tools for NBI, FICE, and i-SCAN will also be required for the use of these techniques to become widespread.

ASGE Technology Committee systematic review and meta-analysis assessing the ASGE PIVI thresholds for adopting real-time endoscopic assessment of the histology of diminutive colorectal polyps.

In vivo real-time assessment of the histology of diminutive (≤5 mm) colorectal polyps detected at colonoscopy can be achieved by means of an "optical biopsy" by using currently available endoscopic technologies. This systematic review and meta-analysis was performed by the American Society for Gastrointestinal Endoscopy (ASGE) Technology Committee to specifically assess whether acceptable performance thresholds outlined by an ASGE Preservation and Incorporation of Valuable endoscopic Innovations (PIVI) document for clinical adoption of these technologies have been met. We conducted direct meta-analyses calculating the pooled negative predictive value (NPV) for narrow-band imaging (NBI), i-SCAN, and Fujinon Intelligent Color Enhancement (FICE)-assisted optical biopsy for predicting adenomatous polyp histology of small/diminutive colorectal polyps. We also calculated the pooled percentage agreement with histopathology when assigning postpolypectomy surveillance intervals based on combining real-time optical biopsy of colorectal polyps 5 mm or smaller with histopathologic assessment of polyps larger than 5 mm. Random-effects meta-analysis models were used. Statistical heterogeneity was evaluated by means of I(2) statistics. Our meta-analyses indicate that optical biopsy with NBI, exceeds the NPV threshold for adenomatous polyp histology, supporting a "diagnose-and-leave" strategy for diminutive predicted nonneoplastic polyps in the rectosigmoid colon. The pooled NPV of NBI for adenomatous polyp histology by using the random-effects model was 91% (95% confidence interval [CI], 88-94). This finding was associated with a high degree of heterogeneity (I(2) = 89%). Subgroup analysis indicated that the pooled NPV was greater than 90% for academic medical centers (91.8%; 95% CI, 89-94), for experts (93%; 95% CI, 91-96), and when the optical biopsy assessment was made with high confidence (93%; 95% CI, 90-96). Our meta-analyses also indicate that the agreement in assignment of postpolypectomy surveillance intervals based on optical biopsy with NBI of diminutive colorectal polyps is 90% or greater in academic settings (91%; 95% CI, 86-95), with experienced endoscopists (92%; 95% CI, 88-96) and when optical biopsy assessments are made with high confidence (91%; 95% CI, 88-95). Our systematic review and meta-analysis confirms that the thresholds established by the ASGE PIVI for real-time endoscopic assessment of the histology of diminutive polyps have been met, at least with NBI optical biopsy, with endoscopists who are expert in using this advanced imaging technology and when assessments are made with high confidence.

Endoscopic submucosal dissection.

ESD is an established effective treatment modality for premalignant and early-stage malignant lesions of the stomach, esophagus, and colorectum. Compared with EMR, ESD is generally associated with higher rates of en bloc, R0, and curative resections and a lower rate of local recurrence. Oncologic outcomes with ESD compare favorably with competing surgical interventions, and ESD also serves as an excellent T-staging tool to identify noncurative resections that will require further treatment. ESD is technically demanding and has a higher rate of adverse events than most endoscopic procedures including EMR. As such,sufficient training is critical to ensure safe conduct and high-quality resections. A standardized training model for Western endoscopists has not been clearly established,but will be self-directed and include courses, animal model training, and optimally an observership at an expert center.Numerous dedicated ESD devices are now available in the United States from different manufacturers. Although the use of ESD in the United States is increasing, issues related to technical difficulty, limited training opportunities and mentors, risk of adverse events, long procedure duration,and suboptimal reimbursement may limit ESD adoption in the United States to a modest number of academic referral centers for the foreseeable future.