Background & Aims:Unchecked inflammation in Eosinophilic esophagitis (EoE) leads to esophageal fibrosis and eventual stricture. Differentiated fibroblasts, termed myofibroblasts, are the main effector cells in fibrosis, responsible for secreting extracellular matrix proteins leading to tissue stiffness. Regulating myofibroblasts has not been explored as a therapeutic possibility in the fibrostenotic esophagus. Herein, we aim to investigate the efficacy of Prostaglandin E2 (PGE2) in dedifferentiation of the EoE myofibroblast. Methods:We evaluated the efficacy and mechanism of myofibroblast dedifferentiation using fetal esophageal fibroblasts (FEF3), patient-derived fibroblasts, and a murine model of EoE. Results:Fibrosis markers (αSMA, FN1, and COL1A1) and contractility of myofibroblasts were significantly decreased by PGE2 via the cAMP pathway. PGE2 treatment decreased nuclear accumulation of phospho-Smad2/3-YAP complex and induced phospho-YAP proteasomal degradation. Transcriptome analyses of FEF3 treated with TGFβ or PGE2 revealed that the Integrin1 pathway, and specifically thrombospondin 1 (THBS-1), was significantly upregulated by TGFβ and downregulated by PGE2, as supported by pseudo-bulk single-cell RNA-seq of EoE biopsies. THBS-1 was shown to be regulated by PGE2 via the cAMP/YAP pathway, and its knockdown induced myofibroblasts dedifferentiation. In a murine model of EoE, Butaprost, agonist of the E-prostanoid G protein-coupled receptor 2, treatment significantly reduced the expression of THBS-1, αSMA, and FN1 along with a decrease in YAP nuclear translocation. Additionally, collagen fiber organization in the lamina propria was markedly reduced. Conclusion:PGE2 promotes dedifferentiation of myofibroblasts in EoE via the cAMP/YAP/THBS-1 pathway. Our data suggest that PGE2 is a promising treatment strategy for EoE with stenosis.

OBJECTIVE:A tracheoesophageal fistula (TEF) is an abnormal communication between the esophagus and trachea, most often associated with esophageal atresia (EA), a rare congenital malformation affecting 1 in 2400-4500 live births. While surgical repair of EA/TEF is typically completed in infancy, recurrent or missed TEF can be diagnosed later. Open repair can be technically challenging, often requiring re-do thoracotomy or neck dissection. We describe our center's experience, using endoscopic electrocautery in combination with esophageal clips for closure of TEF. METHODS:We conducted a retrospective review of all patients who underwent an endoscopic TEF repair with esophageal clip application at our institution (IRB# 20-021016). All patients underwent triple endoscopy (flexible bronchoscopy, esophagogastroduodenoscopy, and rigid bronchoscopy) with pulmonary, gastroenterology (GI), and otolaryngology (ENT). Electrocautery was performed on the tracheal side by ENT or pulmonary and esophageal clip placement by GI. RESULTS:Between November 2019 and February 2025, 14 patients underwent successful endoscopic closure of 15 TEF. One patient failed endoscopic closure of a proximal missed congenital TEF but had successful endoscopic closure of their recurrent TEF. Ten TEF were closed with electrocautery and esophageal clip placement while five were closed with cautery alone. No significant complications occurred, and all closures were confirmed with follow-up endoscopy. CONCLUSION:Endoscopic electrocautery with esophageal clip application, by a skilled multidisciplinary team, offers a minimally invasive alternative to open repair for missed congenital, recurrent, and acquired TEFs. It may be considered as a first line approach, especially in patients with high surgical risk.

BACKGROUND:Patients with esophageal atresia with or without tracheoesophageal fistula (EA-TEF) frequently require fundoplication to manage gastroesophageal reflux disease (GERD). Data is limited on whether fundoplication improves GERD-related outcomes and if outcomes vary by type of fundoplication. METHODS:This is a retrospective cohort study of patients <18 years-old who underwent EA-TEF repair and fundoplication at a single institution from January 2013 to September 2025. In the first aim, we compared GERD symptoms, medications, nutrition, and esophageal stricture dilation rate before and after fundoplication. In the second aim, we compared outcomes between partial and complete fundoplication at 12 months after surgery. RESULTS:Of 226 children with EA-TEF repair, 36 (15.9%) underwent fundoplication, with 14 (38.8%) complete and 22 (61.1%) partial fundoplication. The median age at fundoplication was 7.3 [3.7, 15.9] months. Most patients (69.4%) had Type C EA-TEF. The most common indication was refractory GERD (88.9%). There were no statistical differences in GERD-related symptoms - oral aversion, dysphagia, retching, and vomiting - and medication use when comparing pre-to post-fundoplication. Fundoplication significantly reduced the need for post-pyloric feeds (67% vs 11%, P < 0.001) and improved weight-for-age z-scores (-1.94 vs -1.03, P < 0.001). Fundoplication also decreased the need for stricture dilation (3.07 vs. 1.36 dilations/year, P = 0.001). There were no differences in outcomes between partial and complete fundoplication. Eight patients required fundoplication revision, four from each group. CONCLUSION:In our EA-TEF cohort, fundoplication facilitated conversion from post-pyloric to gastric feeds, decreased stricture burden, and improved nutritional status. Outcomes were not impacted by the type of fundoplication performed.

OBJECTIVE:We aimed to determine the performance of fetal ultrasound in prenatal detection of esophageal atresia/tracheoesophageal fistula (EA/TEF) and evaluate the impact of prenatal diagnosis on postnatal outcomes at a major quaternary care center. METHODS:We conducted a retrospective review of patients who underwent prenatal screening for suspected congenital anomalies at our institution from 2013 to 2024 and included those with prenatal suspicion on ultrasound and/or postnatal diagnosis of EA/TEF (N = 70). We then performed a retrospective cohort analysis of all patients who underwent repair of EA/TEF at our institution, comparing outcomes between those with correct prenatal diagnosis (N = 28) and those with postnatal diagnosis only (N = 168). RESULTS:The sensitivity of fetal ultrasound for prenatal diagnosis of EA/TEF was 48 %, with a positive predictive value (PPV) of 78 %. Sensitivity was 36 % in patients with type C and 100 % in patients with type A. Later gestational age (GA) at ultrasound and presence of fluid-filled esophageal pouch, under-distended/collapsed stomach, and polyhydramnios increased the odds of prenatal diagnosis among patients with type C EA/TEF. There was high concordance between fetal ultrasound and MRI in prenatal detection of EA/TEF. After adjusting for type of EA/TEF, GA at birth, and presence of major cardiac anomalies, there was no difference in age at initial operation, age at discharge, or rate of reoperation. CONCLUSION:Fetal ultrasound has high PPV for prenatal diagnosis of EA/TEF and sensitivity is highly dependent on type of EA/TEF. There are no differences in outcomes between prenatally and postnatally diagnosed patients after adjusting for confounders.

Background: Esophageal atresia (EA) is associated with tracheobronchomalacia (TBM), which in its most severe form, causes blue spells, brief resolved unexplained events (BRUEs) that can require cardiopulmonary resuscitation (CPR), and positive pressure ventilation (PPV) or ventilator dependence, often requiring tracheostomy. We study the role of tracheobronchopexy, as an alternative to tracheostomy, in EA patients with severe life-threatening TBM. Methods: We reviewed EA patients who underwent tracheobronchopexy for blue spells, BRUEs, and failure to wean PPV or extubate from February 2013 to September 2021 at two institutions. Patient characteristics, surgical techniques, and respiratory outcomes were reviewed. Results: 80 EA patients (most Gross type C 92.5 %) underwent 91 tracheobronchopexies at median age 6 (IQR 3-14) months for blue spells/BRUEs (53 %), PPV (21 %), and ventilator dependence (26 %). On preoperative dynamic bronchoscopy, most (90 %) demonstrated complete airway collapse. Surgical approach for tracheobronchopexy was posterior (73 %), anterior (23 %), and simultaneous posterior and anterior (4 %). Tracheobronchopexy included thoracic trachea alone (58 %), trachea and bronchi (41 %), and bronchi alone (1 %). At latest follow up of median 39 (IQR 14-64) months, there were no recurrent blue spells/BRUEs (p < 0.001) and significantly reduced PPV and ventilator dependence (p < 0.001). Nearly all patients (n = 75, 94 %) avoided tracheostomy. Mortality was 5 %, one 30-day operative mortality and three long-term mortalities related to underlying comorbidities. Conclusions: In EA patients with severe life-threatening TBM, tracheobronchopexy significantly reduces blue spells/BRUEs, PPV, and ventilator dependence, and avoids tracheostomy. This surgical strategy should be considered the treatment of choice for EA patients with severe life-threatening TBM symptoms. (c) 2025 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

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.

BackgroundTracheobronchomalacia (TBM) is characterized by excessive dynamic airway collapse. Severe TBM can be associated with substantial morbidity. Children with secondary TBM associated with esophageal atresia/tracheoesophageal fistula (EA/TEF) and vascular-related airway compression (VRAC) demonstrate clinical improvement following airway pexy surgery. It is unclear if children with severe primary TBM, without secondary etiologies (EA/TEF, vascular ring, intrinsic pulmonary pathology, or complex cardiac disease) demonstrate clinical improvement following airway pexy surgery.Materials and MethodsThe study cohort consisted of 73 children with severe primary TBM who underwent airway pexy surgery between 2013 and 2020 at Boston Children's Hospital. Pre- and postoperative symptoms as well as bronchoscopic findings were compared with Fisher exact test for categorical data and Student's t-test for continuous data.ResultsStatistically significant improvements in clinical symptoms were observed, including cough, noisy breathing, prolonged respiratory infections, pneumonias, exercise intolerance, cyanotic spells, brief resolved unexplained events (BRUE), and noninvasive positive pressure ventilation (NIPPV) dependence. No significant differences were seen regarding oxygen dependence, ventilator dependence, or respiratory distress requiring NIPPV. Comparison of pre- and postoperative dynamic bronchoscopy findings revealed statistically significant improvement in the percent of airway collapse in all anatomic locations except at the level of the upper trachea (usually not malacic). Despite some initial improvements, 21 (29%) patients remained symptomatic and underwent additional airway pexies with improvement in symptoms.ConclusionAirway pexy surgery resulted in significant improvement in clinical symptoms and bronchoscopic findings for children with severe primary TBM; however, future prospective and long-term studies are needed to confirm this benefit.

BACKGROUND:Individuals with esophageal atresia (EA) have lifelong increased risk for mucosal and structural pathology of the esophagus. The use of surveillance endoscopy to detect clinically meaningful pathology has been underexplored in pediatric EA. We hypothesized that surveillance endoscopy in pediatric EA has high clinical yield, even in the absence of symptoms.STUDY DESIGN:The medical records of all patients with EA who underwent at least 1 surveillance endoscopy between March 2004 and March 2023 at an international EA referral center were retrospectively reviewed. The primary outcomes were endoscopic identification of pathology leading to an escalation in medical, endoscopic, or surgical management. Logistic regression analysis examined predictors of actionable findings. Nelson-Aalen analysis estimated optimal endoscopic surveillance intervals.RESULTS:Five hundred forty-six children with EA underwent 1,473 surveillance endoscopies spanning 3,687 person-years of follow-up time. A total of 770 endoscopies (52.2%) in 394 unique patients (72.2%) had actionable pathology. Esophagitis leading to escalation of therapy was the most frequently encountered finding (484 endoscopies, 32.9%), with most esophagitis attributed to acid reflux. Barrett's esophagus (intestinal metaplasia) was identified in 7 unique patients (1.3%) at a median age of 11.3 years. No dysplastic lesions were identified. Actionable findings leading to surgical intervention were found in 55 children (30 refractory reflux and 25 tracheoesophageal fistulas). Significant predictors of actionable pathology included increasing age, long gap atresia, and hiatal hernia. Symptoms were not predictive of actionable findings, except dysphagia, which was associated with stricture. Nelson-Aalen analysis predicted occurrence of an actionable finding every 5 years.CONCLUSIONS:Surveillance endoscopy uncovers high rates of actionable pathology even in asymptomatic children with EA. Based on the findings of the current study, a pediatric EA surveillance endoscopy algorithm is proposed.

Historically, children afflicted with long gap esophageal atresia (LGEA) had few options, either esophageal replacement or a life of gastrostomy feeds. In 1997, John Foker from Minnesota revolutionized the treatment of LGEA. His new procedure focused on "traction-induced growth" when the proximal and distal esophageal segments were too far apart for primary repair. Foker's approach involved placement of pledgeted sutures on both esophageal pouches connected to an externalized traction system which could be serially tightened, allowing for tension-induced esophageal growth and a delayed primary repair. Despite its potential, the Foker process was received with criticism and disbelief, and to this day, controversy remains regarding its mechanism of action - esophageal growth versus stretch. Nonetheless, early adopters such as Rusty Jennings of Boston embraced Foker's central principle that "one's own esophagus is best" and was instrumental to the implementation and rise in popularity of the Foker process. The downstream effects of this emphasis on esophageal preservation would uncover the need for a focused yet multidisciplinary approach to the many challenges that EA children face beyond "just the esophagus", leading to the first Esophageal and Airway Treatment Center for children. Consequently, the development of new techniques for the multidimensional care of the LGEA child evolved such as the posterior tracheopexy for associated tracheomalacia, the supercharged jejunal interposition, as well as minimally invasive internalized esophageal traction systems. We recognize the work of Foker and Jennings as key catalysts of an era of esophageal preservation and multidisciplinary care of children with EA.

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.

Background: Anastomotic strictures (AS) after esophageal atresia (EA) repair are common. While most respond to endoscopic therapy, some become refractory and require surgical intervention, for which the outcomes are not well established.Methods: All EA children with AS who were treated surgically at two institutions (2011-2022) were retrospectively reviewed. Surgical repair was performed for those with AS that were either refractory to endoscopic therapy or clinically symptomatic and undergoing surgery for another indication. Anastomotic leak, need for repeat stricture resection, and esophageal replacement were considered poor outcomes.Results: 139 patients (median age: 12 months, range 1.5 months-20 years; median weight: 8.1 kg) underwent 148 anastomotic stricture repairs (100 refractory, 48 non-refractory) in the form of stricturoplasty (n = 43), segmental stricture resection with primary anastomosis (n = 96), or stricture resection with a delayed anastomosis after traction-induced lengthening (n = 9). With a median followup of 38 months, most children (92%) preserved their esophagus, and the majority (83%) of stricture repairs were free of poor outcomes. Only one anastomotic leak occurred in a non-refractory stricture. Of the refractory stricture repairs (n = 100), 10% developed a leak, 9% required repeat stricture resection, and 13% required esophageal replacement. On multivariable analysis, significant risk factors for any type of poor outcome included anastomotic leak, stricture length, hiatal hernia, and patient's weight.Conclusions: Surgery for refractory AS is associated with inherent yet low morbidity and high rates of esophageal preservation. Surgical repair of non-refractory symptomatic AS at the time of another thoracic operation is associated with excellent outcomes. Level of Evidence: Level III.(c) 2023 Elsevier Inc. All rights reserved.

Harvard Medical School, USA; The Children's Hospital of Philadelphia, USA; Johns Hopkins All Children's Hospital, USA; Boston Children's Hospital, USA.

Background: Left-sided repair for long gap esophageal atresia (LGEA) has been described for patients with a large leftward upper pouch, no thoracic tracheoesophageal fistula (TEF) nor tracheo-bronchomalacia (TBM), or as salvage plan after prior failed right-sided repair. We describe our experience with left-sided MIS traction induced growth process.Methods: We retrospectively reviewed patients who underwent Foker process for LGEA at two in-stitutions between December 2016 and November 2021. Patient characteristics, surgical techniques, and outcomes were reviewed. Results: 71 patients underwent Foker process. Of 34 MIS cases, 28 patients (82%) underwent left-sided repair (median gap length 5 cm) at median age 4 months with median 3 (range 2-8) operations and median 13.5 (IQR 11-21) days on traction until esophageal anastomosis. 9 patients (32%) underwent completely MIS approach, whereas 5 patients (18%) converted to open at first operation and 14 patients (50%) converted to open later in the traction process. Traction was internal in 68%, external in 11%, and combination in 21%. Median follow-up was 15.4 (IQR 7.5-31.7) months after anastomosis. 14% had anastomotic leak managed with antibiotics and/or esophageal vacuum therapy. Median number of esophageal dilations was 3.5 (range 0-13). 18% required stricture resection. 39% underwent Nissen fundoplication. None have needed esophageal replacement. Conclusions: For multiple reasons including the tendency of both esophageal pouches to have a leftward bias, less tracheal compression by upper pouch, and clean field of surgery for reoperative cases, we now more commonly use left-sided approach for MIS LGEA repair compared to right side, regardless of left aortic arch. Level of evidence: Level IV Treatment Study.(c) 2022 Elsevier Inc. All rights reserved.

PURPOSE The safety of reintroducing chemotherapy in the pediatric renal tumor setting after severe hepatopathy (SH), including sinusoidal obstruction syndrome (SOS), is uncertain. We describe the incidence, severity, outcomes, and impact on subsequent treatment for patients with SH from National Wilms Tumor Study (NWTS) protocols 3-5. PATIENTS AND METHODS Archived charts for patients enrolled on NWTS 3-5 who met study inclusion criteria for SH by using established hepatopathy grading scales and clinical criteria were reviewed for demographics, tumor characteristics, radio- and chemotherapy details, SH-related dose modifications, and oncologic outcomes. Genomic analysis for candidate polymorphisms associated with SH was performed in 14 patients. RESULTS Seventy-one of 8,862 patients (0.8%) met study inclusion criteria. The median time from therapy initiation to SH was 51 days (range, 2-293 days). Sixty percent received radiotherapy, and 56% had right-sided tumors. Grade 1-4 thrombocytopenia was noted in 70% at initial occurrence of SH (median 22,000/microliter). Among 69 of 71 children with SH occurring before the end of therapy (EOT) and post-SH treatment information available, chemotherapy was delayed posthepatopathy for 65% (69% of these at a reduced dose), continued without delay for 20% (57% of these at reduced dose), and stopped completely for 15% (4 of 10 of whom died of SH). Overall, 42% of patients with dose reductions achieved full dose by EOT. The five-year post-SH event-free survival for patients who continued therapy was 89% (95% CI, 81 to 98), with no significant differences by whether delay or dose reduction occurred. We identified no SH-associated pharmacogenomic polymorphism. CONCLUSION The incidence of SH on NWTS 3-5 was low; many had associated severe thrombocytopenia. Careful reintroduction of chemotherapy appeared to be feasible for the majority of patients who developed severe chemotherapy- and/or radiotherapy-induced liver toxicity.

Background: Indocyanine green (ICG) is commonly used to assess perfusion, but quality defining features are lacking. We sought to establish qualitative features of esophageal ICG perfusion assessments, and develop an esophageal anastomotic scorecard to risk-stratify anastomotic outcomes. Methods: Single institution, retrospective analysis of children with an intraoperative ICG perfusion as-sessment of an esophageal anastomosis. Qualitative perfusion features were defined and a perfusion score developed. Associations between perfusion and clinical features with poor anastomotic outcomes (PAO, leak or refractory stricture) were evaluated with logistic and time-to-event analyses. Combining signifi-cant features, we developed and tested an esophageal anastomotic scorecard to stratify PAO risk. Results: From 2019 to 2021, 53 children (median age 7.4 months) underwent 55 esophageal anasto-moses. Median (IQR) follow-up was 14 (10-19.9) months; mean (SD) perfusion score was 13.2 (3.4). Fif-teen (27.3%) anastomoses experienced a PAO and had significantly lower mean perfusion scores (11.3 (3.3) vs 14.0 (3.2), p = 0.007). Unique ICG perfusion features, severe tension, and primary or rescue traction-induced esophageal lengthening [Foker] procedures were significantly associated with PAO on both lo-gistic and Cox regression. The scorecard (range 0-7) included any Foker ( + 2), severe tension ( + 1), no arborization on either segment ( + 1), suture line hypoperfusion > twice expected width ( + 2), and seg-mental or global areas of hypoperfusion ( + 1). A scorecard cut-off >3 yielded a sensitivity of 73% and specificity of 93% (AUC 0.878 [95%CI 0.777 to 0.978]) in identifying a PAO. Conclusions: A scoring system comprised of qualitative ICG perfusion features, tissue quality, and anasto-motic tension can help risk-stratify esophageal anastomotic outcomes accurately. Levels of Evidence: Diagnostic -II & COPY; 2022 Elsevier Inc. All rights reserved.

ABSTRACT 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 (Δ D ). A receiver operating characteristic (ROC) curve analysis was performed to determine the discriminatory ability of Δ D . 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 Δ D 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.

Background: Anti-reflux procedures (ARP) in esophageal atresia (EA) patients can be challenging and prone to failure. These challenges become more evident with increasing complexity of EA. We sought to determine predictors of ARP failure in complex EA patients. Methods: Single-institution retrospective review of complex EA patients (e.g. long-gap EA, esophageal strictures, hiatal hernia, and reoperative ARP) who underwent an ARP from 2002 to 2019. ARP failure was defined as hiatal hernia recurrence, wrap migration/loosening, or need for reoperation. Predictors of failure were evaluated using univariate and multivariable time-to-event analysis. Results: 121 patients underwent 140 ARP at a median age of 13.5 months (IQR 7, 26.5). Nissen fundoplication (89%) was the most common ARP. Mesh (bovine pericardium) reinforcement was used in 41% of the patients. Median follow-up was 3.2 years (IQR 0.9, 5.8); 44 instances of ARP failure occurred (31%), though only 20 (14%) required reoperation. Median time to failure was 8.7 months (IQR 3.2, 25). Though fewer mesh-reinforced ARP failed (21% with vs 39% without, p = 0.02), on multivariable analysis only partial fundoplication (aHR 2.22 [95% CI 1.01-4.78]) and minimally invasive repair (aHR 2.57 [95% CI 1.12-6.01]) were significant predictors of ARP failure. Conclusion: In our practice of complex EA patients, where ARP fail in nearly one third of cases, a Nissen fundoplication performed via laparotomy provided the lowest risk of ARP failure. (C) 2021 Elsevier Inc. All rights reserved.

Diffuse hyperplastic perilobar nephroblastomatosis (DHPLN) represents a unique category of nephroblastomatosis. Treatment has ranged from observation to multiple regimens of chemotherapy. Wilms tumors (WTs) develop in 100% of untreated patients and between 32 and 52% of treated patients. Renal preservation rates have not been previously reported. An aim of the Children’s Oncology Group (COG) study AREN0534 was to prospectively evaluate the efficacy of chemotherapy in preserving renal units and preventing WT development in children with DHPLN. Patients were enrolled through the COG protocol AREN03B2 with central radiological review. DHPLN was defined as the cortical surface of the kidney being composed of hyperplastic rests, with the entire nephrogenic zone involved, and with a thick rind capping all of one or both kidneys. Treatment was with vincristine and dactinomycin (regimen EE4A), with cross-sectional imaging at weeks 6 and 12. If the patient’s disease was stable or decreasing, treatment was continued for 19 weeks. Renal preservation, WT development rates at 1 year, and overall survival (OS) are reported. Nine patients were enrolled (five females and four males), with a median age at enrollment of 10.22 months (range 2.92–29.11). One patient who was enrolled was deemed unevaluable because they did not meet the radiological criteria for DHPLN, resulting in eight evaluable patients. These eight patients had DHPLN confirmed via radiological criteria (all bilateral). Initial chemotherapy was EE4A for all eight patients, with seven of eight patients starting chemotherapy without tissue diagnosis.One patient who had an upfront partial nephrectomy was found to have DHPLN in the specimen and was subsequently treated with EE4A. All patients remained alive, with a median follow-up of 6.6 years (range 4.5–9.1). No patients were anephric; 14 of 16 kidneys were functioning (87.5%). Six of eight patients (75%) did not have WT on therapy, but two of these patients relapsed within 6 months of stopping therapy; both had favorable histology WT. One patient who was diagnosed with WT on therapy relapsed at 12 months (one of eight [12.5%]) and developed anaplastic histology. Chemotherapy for patients with DHPLN was effective in preserving kidney function. Five-year OS is excellent, however the ideal type and duration of chemotherapy to prevent WT development remains elusive.

A patient developed the severe amnesic syndrome 8 years after temporal lobe surgery for epilepsy. He underwent left temporal lobectomy (6 cm, 43.5 g; hippocampal sclerosis) aged 19, and remained seizure free for 8 years until a convulsion followed a head injury. He became severely amnesic after a fourth convulsion 16 months later. He was right-handed, pre-operative IQ was average, verbal memory poor and non-verbal memory normal. Post-operatively, these were unchanged. After the first post-operative seizure he began professional training. After onset of amnesia IQ was unchanged, anterograde memory severely impaired and retrograde amnesia dense for at least 16 months. He died 2 years later. Magnetic resonance imaging before amnesia showed absence of anterior left temporal lobe, atrophy of left fornix and mamillary body, and normal right temporal lobe. Four months after onset of amnesia, right hippocampal volume had reduced by 36%. Autopsy showed: previous left temporal lobectomy with absence of left amygdala and hippocampus, atrophy of fornix and mamillary body; neuronal loss in the right hippocampus, severe in CA1 and CA4; intact right amygdala and parahippocampal gyrus; recent diffuse damage associated with cause of death. A convulsion can cause severe hippocampal damage in adult life. Hippocampal zones CA1 and/or CA4 are critical for maintaining memory and the amygdala and parahippocampal gyrus cortex alone cannot support acquisition of new memories.