Peter Ngo

Eosinophils in the Esophagus—Peptic or Allergic Eosinophilic Esophagitis? Case Series of Three Patients with Esophageal Eosinophilia

OBJECTIVES:Scattered eosinophils in the distal esophagus traditionally provide the hallmark for peptic esophagitis, but the upper limit of eosinophils and the longitudinal extent of peptic inflammation along the esophagus are unknown. Recently, adults and children with upper intestinal symptoms and >20 eosinophils/high-power field (eos/HPF) have been given the diagnosis of allergic esophagitis. Standardized diagnostic criteria for allergic esophagitis are lacking and the isolated finding of large numbers of eosinophils in the squamous epithelium has been used as the defining feature. We cared for three patients with symptoms and endoscopic features of esophagitis with >20 eos/HPF in their esophageal mucosa. Symptoms, endoscopic features, and histologic findings resolved after 2 months of proton pump inhibitor (PPI) treatment. The aim of this case series is to demonstrate that features thought to be consistent with a diagnosis of allergic esophagitis are also observed in peptic esophagitis.METHODS:A retrospective chart review of three patients with esophagitis (>20 eos/HPF) whose symptoms and eosinophilia resolved with PPI treatment was performed. Esophageal biopsies were reviewed in a blinded manner by one pathologist.RESULTS:Patients (aged 14, 25, and 5 yr) presented with dysphagia, food impaction, and vomiting. Endoscopic features included white exudates and linear furrows. None of the patients received antiallergic treatments or dietary eliminations prior to endoscopy. Following treatment with PPIs alone, all patients became asymptomatic and endoscopic findings reverted to normal. In all three patients, pre- and post-PPI treatment eosinophil numbers/HPF decreased to normal/near normal (37 to 1, 21 to 3, and 52 to 0 eosinophils/HPF in patients 1, 2, and 3, respectively).CONCLUSION:Large numbers of eosinophils can be seen in peptic esophagitis. This histologic finding must be interpreted in the context of the clinical setting in which it is obtained.

Collagen gel contraction assay.

Mucosal tissues undergo contraction and relaxation on a continuous basis. In its normal state, the pliable intestinal tract is characterized by a rhythmic pattern of contractions controlled by its intrinsic neuronal innvervation. In chronic inflammatory diseases such as Crohns disease, the intestine can become stiff and fibrotic, losing much of its normal motility. Although muscle fiber contraction accounts for much of this activity, contraction of nonmuscle tissue is constantly occurring in events associated with chronic inflammation, such as wound healing, scar formation, and tissue remodeling. However, the physiological and pathological mechanisms defining these events are not well defined. Tissue contraction is a dynamic event characterized by both intracellular and extracellular events. A number of cells, such as fibroblasts, epithelial cells, lymphocytes, and eosinophils, normally reside within the gastrointestinal tract. Additionally, the extracellular matrix is composed of a complex infrastructure that includes collagen and other molecules. The manner in which these two components interact is not certain, but the use of recent model systems has provided insights into these processes. The collagen lattice contraction assay provides a model for tissue contraction that takes advantage of the finding that cell-populated collagen hydrogels contract over time in a predictable, consistent manner. This model allows for investigation of the influence of specific agonists on the rate and extent of matrix contraction.

Paediatric Research in Emergency Departments International Collaborative (PREDICT): First steps towards the development of an Australian and New Zealand research network

Paediatric emergency research is hampered by a number of barriers that can be overcome by a multicentre approach. In 2004, an Australia and New Zealand‐based paediatric emergency research network was formed, the Paediatric Research in Emergency Departments International Collaborative (PREDICT). The founding sites include all major tertiary childrens hospital EDs in Australia and New Zealand and a major mixed ED in Australia. PREDICT aims to provide leadership and infrastructure for multicentre research at the highest standard, facilitate collaboration between institutions, health‐care providers and researchers and ultimately improve patient outcome. Initial network‐wide projects have been determined. The present article describes the development of the network, its structure and future goals.

Emergency management of paediatric status epilepticus in Australia and New Zealand: practice patterns in the context of clinical practice guidelines.

Aims:  To establish current acute seizure management through a review of clinical practice guidelines (CPGs) and reported physician management in the 11 largest paediatric emergency departments in Australia (n= 9) and New Zealand (n= 2) within the Paediatric Research in Emergency Departments International Collaborative (PREDICT) network, and to compare this with Advanced Paediatric Life Support (APLS) guidelines and existing evidence.

Foker process for the correction of long gap esophageal atresia: Primary treatment versus secondary treatment after prior esophageal surgery

PURPOSE The Foker process (FP) uses tension-induced growth for primary esophageal reconstruction in patients with long gap esophageal atresia (LGEA). It has been less well described in LGEA patients who have undergone prior esophageal reconstruction attempts. METHODS All cases of LGEA treated at our institution from January 2005 to April 2014 were retrospectively reviewed. Patients who initially had esophageal surgery elsewhere were considered secondary FP cases. Demographics, esophageal evaluations, and complications were collected. Median time to esophageal anastomosis and full oral nutrition was estimated using the Kaplan-Meier method. Multivariate Cox-proportional hazards regression identified potential risk factors. RESULTS Fifty-two patients were identified, including 27 primary versus 25 secondary FP patients. Median time to anastomosis was 14 days for primary and 35 days for secondary cases (p<0.001). Secondary cases (p=0.013) and number of thoracotomies (p<0.001) were identified as significant predictors for achieving anastomosis and the development of a leak. Predictors of progression to full oral feeding were primary FP cases (O.R.=17.0, 95% CI: 2.8-102, p<0.001) and patients with longer follow-up (O.R.=1.06/month, 95% CI: 1.01-1.11, p=0.005). CONCLUSIONS The FP has been successful in repairing infants with primary LGEA, but the secondary LGEA patients proved to be more challenging to achieve a primary esophageal anastomosis. Early referral to a multidisciplinary esophageal center and a flexible approach to establish continuity in secondary patients is recommended. Given their complexity, larger studies are needed to evaluate long-term outcomes and discern optimal strategies for reconstruction.

Comparison of 2 delivery vehicles for viscous budesonide to treat eosinophilic esophagitis in children.

Objectives: Oral viscous budesonide (OVB) using Splenda as a delivery vehicle has become an attractive therapeutic option for children with eosinophilic esophagitis (EoE). Many families are wary of giving the artificial sweetener in high doses to their children. The aim of the present study was to determine whether OVB mixed with Neocate Nutra, a hypoallergenic nutritional supplement, is at least as efficacious as OVB mixed with Splenda at healing EoE. Methods: Our institutional review board approved a retrospective chart review of patients with well-documented EoE treated with OVB at the Boston Childrens Hospital Eosinophilic Gastrointestinal Disorder program between June 2008 and June 2013. Primary outcome measured was histologic response defined as change in peak eosinophil count to <15 eosinophils per high-power field (eos/HPF) after at least 10 weeks of OVB therapy. Results: A total of 46 children were treated with OVB mixed with Splenda, and 14 were treated with OVB mixed with Neocate Nutra. The 2 groups were not significantly different in their demographic (race, age, sex) or clinical (initial eosinophil count, proton pump inhibitor use, or concomitant dietary elimination) characteristics. On follow-up endoscopy, 30 of 46 patients on Splenda and 13 of 14 patients on Neocate Nutra achieved histologic response. Mean pretreatment and posttreatment peak eosinophil counts for the children taking Neocate Nutra were 62 eos/HPF ([high-power field] range 20–120 eos/HPF) and 9 eos/HPF (range 0–100 eos/HPF), respectively. Mean pretreatment and posttreatment peak eosinophil counts for the Splenda group were 59.5 eos/HPF (range 20–180 eos/HPF) and 25.5 eos/HPF (range 0–200 eos/HPF), respectively. The odds ratio (OR) of success with Neocate Nutra as compared with Splenda was 6.93 (95% CI 0.83–57.91, P = 0.0728), demonstrating the noninferiority of Neocate Nutra. Conclusions: We demonstrate that OVB mixed with Neocate Nutra is at least as effective as OVB mixed with Splenda at treating children with EoE. Neocate Nutra is an innovative, effective, and palatable mixing agent to create a viscous budesonide slurry for families who prefer not to use the standard recipe with Splenda.

Assessment of Fractionated Exhaled Nitric Oxide as a Biomarker for the Treatment of Eosinophilic Esophagitis

Diagnosis of eosinophilic esophagitis (EoE) and determination of response to therapy is based on histological assessment of the esophagus, which requires upper endoscopy. In children, in whom a dietary approach is commonly used, multiple endoscopies are needed, because foods are eliminated and then gradually reintroduced. Ideally, noninvasive methods could supplement or replace upper endoscopy to facilitate management. Fractionated exhaled nitric oxide (FeNO) has been proposed as a useful measure for monitoring disease activity in studies of patients with eosinophil-predominant asthma and in other atopic disorders. Thus, we evaluated whether FeNO levels could be a useful biomarker to assess the response to therapy in EoE patients. This study was designed to determine whether there is a change in FeNO levels during treatment with topical corticosteroids and whether changes correlated with clinical response. This was a prospective, multicenter study that enrolled nonasthmatic patients with established EoE. FeNO levels and symptom scores were measured at baseline, biweekly during 6-week swallowed fluticasone treatment, and 4 weeks posttreatment. Twelve patients completed the trial. We found a statistically significant difference between median pre- and posttreatment FeNO levels [20.3 ppb (16.0 -29.0 ppb) vs 17.6 ppb (11.7 -27.3 ppb), [corrected] p=0.009]. However, neither the pretreatment FeNO level, a change of FeNO level after 2 weeks of treatment, nor the FeNO level at the end of treatment confidently predicted a clinical or histological response. Although our findings suggest nitric oxide possibly has a physiological role in EoE, our observations do not support a role of FeNo determination for management of EoE.

Categorization and repair of recurrent and acquired tracheoesophageal fistulae occurring after esophageal atresia repair

PURPOSE Recurrent trachea-esophageal fistula (recTEF) is a frequent (5%-10%) complication of congenital TEF (conTEF) and esophageal atresia (EA) repair. In addition, postoperative acquired TEF (acqTEF) can occur in addition to or even in the absence of prior conTEF in the setting of esophageal anastomotic complications. Reliable repair often proves difficult by endoluminal or standard surgical techniques. We present the results of an approach that reliably identifies the TEF and facilitates airway closure as well as repair of associated tracheal and esophageal problems. METHODS Retrospective review of 66 consecutive patients 2009-2016 (55 referrals and 11 local) who underwent repair via reoperative thoracotomy or cervicotomy for recTEF and acqTEF (IRB P00004344). Our surgical approach used complete separation of the airway and esophagus, which reliably revealed the TEF (without need for cannulation) and freed the tissues for primary closure of the trachea and frequently resection of the tracheal diverticulum. For associated esophageal strictures, stricturoplasty or resection was performed. Separation of the suture lines by rotational pexy of the both esophagus and the trachea, and/or tissue interposition were used to further inhibit re-recurrence. For associated severe tracheomalacia, posterior tracheopexy to the anterior spinal ligament was utilized. RESULTS The TEFs were recurrent (77%), acquired from esophageal leaks (26%), in addition to persistent or missed H-type (6%). Seven patients in this series had multiple TEFs of more than one category. Of the acqTEF cases, 6 were esophagobronchial, 10 esophagopulmonic, 2 esophagotracheal (initial pure EA cases), and 2 from a gastric conduit to the trachea. Upon referral, 18 patients had failed endoluminal treatments; and open operations for recTEF had failed in 18 patients. Significant pulmonary symptoms were present in all. During repairs, 58% were found to have a large tracheal diverticulum, and 51% had posterior tracheopexy for significant tracheomalacia. For larger esophageal defects, 32% were treated by stricturoplasty and 37% by segmental resection. Rotational pexy of the trachea and/or esophagus was utilized in 62% of cases to achieve optimal suture line separation. Review with a mean follow-up of 35months identified no recurrences, and resolution of pulmonary symptoms in all. Stricture treatment required postoperative dilations in 30, and esophageal replacement in 6 for long strictures. There was one death. CONCLUSION This retrospective review of 66 patients with postoperative recurrent and acquired TEF following esophageal atresia repair is the largest such series to date and provides a new categorization for postoperative TEF that helps clarify the diagnostic and therapeutic challenges for management.

Small bowel intussusception in celiac disease: revisiting a classic association.

r JP us emesis. She had an upper respiratory infection 2 weeks before admission, but was table for a distended abdomen with diffuse epigastric tenderness. An abdominal radiograph suggested a small bowel obstruction, and a computed tomography scan (Fig. 1) confirmed multiple dilated loops of small bowel, ascites, and an enlarged, fluid-filled enhancing appendix. At exploratory laparoscopy, she had 6 discrete small bowel intussusceptions (Fig. 2) that were easily reduced and a normal appendix. Subsequent celiac serological testing (tissue transglutaminase >100) and endoscopic biopsies were diagnostic.

Robotic implant to apply tissue traction forces in the treatment of esophageal atresia

This paper introduces robotic implants as a novel class of medical robots in the context of treating esophageal atresia. The robotic implant is designed to apply traction forces to the two disconnected esophageal segments to induce sufficient growth so that the two ends can be joined together to form a functioning esophagus. In contrast to the current manual method of externally applying traction forces, the implant offers the potential to avoid prolonged patient sedation and to substantially reduce the number of X-rays required. A prototype design is presented along with evaluation experiments that demonstrate its capabilities to apply traction forces to ex vivo esophageal tissues.