Victor L. Fox

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.

Eosinophilic esophagitis: It's not just kid's stuff

Increasing evidence suggests that the esophagus serves as both a conduit for food and a participant in immune responses.1-6 This complex structure possesses innate elements of defense and orchestrates the migration of inflammatory cells, such as lymphocytes and eosinophils, into the squamous epithelium. In that regard, recent clinical experiences have identified an emerging entity termed eosinophilic esophagitis (EE). Although it is thought to occur primarily in children, a significant body of evidence suggests EE affects adults as well. Diagnostic clues are often detected in the gross appearance of the esophageal mucosa, thus emphasizing the important role of GI endoscopists in recognizing this disease. To complete this review of EE, the MEDLINE database was searched for articles containing the words “eosinophilic esophagitis,” “allergic esophagitis,” “ringed,” or “corrugated esophagus.” This search yielded 83 articles dating back to 1978. Review articles, articles lacking any details of the esophageal histology, and those reporting eosinophilic esophagitis in association with eosinophilic gastroenteritis were excluded. Twenty-nine articles and 3 abstracts detailing the experiences of gastroenterologists, pathologists, allergists, and radiologists with 186 patients with EE (35% adults) were examined and form the basis for the clinical details of this article.4,7-37 In addition, 5 investigations examined the immunopathology and pathogenesis of this condition.4,10,38-40 More than two thirds of the articles were published during the last 5 years.

Allergic esophagitis in children: a clinicopathological entity.

Infiltration of esophageal epithelium by eosinophils is seen in reflux esophagitis and allergic gastroenteritis. This study was performed to identify differences between patients with acid reflux esophagitis and those with non-acid reflux, possibly allergic, esophagitis. Intraepithelial eosinophils were demonstrated in posttherapy esophageal biopsy specimens in 28 children treated for gastroesophageal reflux disease (GERD). These patients were divided into three groups based on their response to treatment and the results of esophageal pH probe monitoring. Eleven patients (Group A) had incomplete clinical response and normal pH probe monitoring results. Ten patients (Group B) had incomplete response but did not have pH probe monitoring. These two groups formed the index population. Seven patients (Group C) had clinical improvement with GERD therapy and abnormal pH probe monitoring characteristic of GERD; they constituted the control population. Clinical, laboratory, and pathologic features were evaluated to detect differences between index and control populations. Dysphagia, food impaction, failure to thrive, peripheral eosinophilia, and abnormal allergen skin test results were detected only in Group A and B patients. Biopsy specimens of the distal 9 cm of the esophagus, after GERD therapy, contained larger numbers of eosinophils in Groups A and B than in Group C as shown on high-power fields (HPF) (A: 31/HPF +/- 19.5; B: 28/HPF +/-23.7; versus C: 5/HPF +/-6.7; p = 0.009). Eosinophil aggregates were identified only in Groups A and B (p = 0.07). Eosinophils located preferentially in the superficial layers of the squamous epithelium were noted only in Groups A and B (p = 0.02). Group A and B patients demonstrated clinical improvement when given antiallergic therapy. The authors identified a group of pediatric patients characterized by an allergic history, lack of adequate response to GERD therapy, normal esophageal pH probe monitoring results, and large numbers of eosinophils in esophageal biopsy specimens obtained after GERD treatment. On the basis of these features, the authors propose that these patients represent examples of allergic esophagitis.

Microstream Capnography Improves Patient Monitoring During Moderate Sedation: A Randomized, Controlled Trial

BACKGROUND. Investigative efforts to improve monitoring during sedation for patients of all ages are part of a national agenda for patient safety. According to the Institute of Medicine, recent technological advances in patient monitoring have contributed to substantially decreased mortality for people receiving general anesthesia in operating room settings. Patient safety has not been similarly targeted for the several million children annually in the United States who receive moderate sedation without endotracheal intubation. Critical event analyses have documented that hypoxemia secondary to depressed respiratory activity is a principal risk factor for near misses and death in this population. Current guidelines for monitoring patient safety during moderate sedation in children call for continuous pulse oximetry and visual assessment, which may not detect alveolar hypoventilation until arterial oxygen desaturation has occurred. Microstream capnography may provide an “early warning system” by generating real-time waveforms of respiratory activity in nonintubated patients. OBJECTIVE. The aim of this study was to determine whether intervention based on capnography indications of alveolar hypoventilation reduces the incidence of arterial oxygen desaturation in nonintubated children receiving moderate sedation for nonsurgical procedures. PARTICIPANTS AND METHODS. We included 163 children undergoing 174 elective gastrointestinal procedures with moderate sedation in a pediatric endoscopy unit in a randomized, controlled trial. All of the patients received routine care, including 2-L supplemental oxygen via nasal cannula. Investigators, patients, and endoscopy staff were blinded to additional capnography monitoring. In the intervention arm, trained independent observers signaled to clinical staff if capnograms indicated alveolar hypoventilation for >15 seconds. In the control arm, observers signaled if capnograms indicated alveolar hypoventilation for >60 seconds. Endoscopy nurses responded to signals in both arms by encouraging patients to breathe deeply, even if routine patient monitoring did not indicate a change in respiratory status. OUTCOME MEASURES. Our primary outcome measure was patient arterial oxygen desaturation defined as a pulse oximetry reading of <95% for >5 seconds. Secondary outcome measures included documented assessments of abnormal ventilation, termination of the procedure secondary to concerns for patient safety, as well as other more rare adverse events including need for bag-mask ventilation, sedation reversal, or seizures. RESULTS. Children randomly assigned to the intervention arm were significantly less likely to experience arterial oxygen desaturation than children in the control arm. Two study patients had documented adverse events, with no procedures terminated for patient safety concerns. Intervention and control patients did not differ in baseline characteristics. Endoscopy staff documented poor ventilation in 3% of all procedures and no apnea. Capnography indicated alveolar hypoventilation during 56% of procedures and apnea during 24%. We found no change in magnitude or statistical significance of the intervention effect when we adjusted the analysis for age, sedative dose, or other covariates. CONCLUSIONS. The results of this controlled effectiveness trial support routine use of microstream capnography to detect alveolar hypoventilation and reduce hypoxemia during procedural sedation in children. In addition, capnography allowed early detection of arterial oxygen desaturation because of alveolar hypoventilation in the presence of supplemental oxygen. The current standard of care for monitoring all patients receiving sedation relies overtly on pulse oximetry, which does not measure ventilation. Most medical societies and regulatory organizations consider moderate sedation to be safe but also acknowledge serious associated risks, including suboptimal ventilation, airway obstruction, apnea, hypoxemia, hypoxia, and cardiopulmonary arrest. The results of this controlled trial suggest that microstream capnography improves the current standard of care for monitoring sedated children by allowing early detection of respiratory compromise, prompting intervention to minimize hypoxemia. Integrating capnography into patient monitoring protocols may ultimately improve the safety of nonintubated patients receiving moderate sedation.

A genetic screen identifies an LKB1–MARK signalling axis controlling the Hippo–YAP pathway

The Hippo–YAP pathway is an emerging signalling cascade involved in the regulation of stem cell activity and organ size. To identify components of this pathway, we performed an RNAi-based kinome screen in human cells. Our screen identified several kinases not previously associated with Hippo signalling that control multiple cellular processes. One of the hits, LKB1, is a common tumour suppressor whose mechanism of action is only partially understood. We demonstrate that LKB1 acts through its substrates of the microtubule affinity-regulating kinase family to regulate the localization of the polarity determinant Scribble and the activity of the core Hippo kinases. Our data also indicate that YAP is functionally important for the tumour suppressive effects of LKB1. Our results identify a signalling axis that links YAP activation with LKB1 mutations, and have implications for the treatment of LKB1-mutant human malignancies. In addition, our findings provide insight into upstream signals of the Hippo–YAP signalling cascade.

Blue Rubber Bleb Nevus Syndrome: Surgical Eradication of Gastrointestinal Bleeding

Objective:We report the largest clinical experience to date of surgically treated patients with blue rubber bleb nevus syndrome (BRBNS). Summary Background Data:BRBNS is a rare congenital disorder presenting with multifocal venous malformations of the skin, soft tissues, and gastrointestinal (GI) tract. Patients with BRBNS develop anemia from chronic GI bleeding, and require lifelong treatment with iron and blood transfusions. An aggressive surgical approach to treat the GI venous malformations of BRBNS has been considered unlikely to be successful because of the large number of lesions, their position throughout the GI tract, and the likelihood of recurrence. Based on our belief that eradicated lesions would not recur, we undertook the removal of all GI tract lesions in an effort to eliminate bleeding. Methods:Ten patients with BRBNS were treated from 1993 to 2002. Lesions were identified using complete GI endoscopy. The multiple venous malformations were removed by a combination of wedge resection, polypectomy, suture-ligation, segmental bowel resection, and band ligation. Results:Patient ages ranged from 2 to 36 years, and patients received an average of 53 prior blood transfusions. A mean of 137 focal GI venous malformations per patient were resected at operation (range 4–557), with a mean operative duration of 14 hours (range 7–23 hours). Only 1 patient who had a less extensive procedure developed recurrent GI bleeding. The mean follow-up period was 5.0 years (range 2.9–10.3 years). Conclusions:We believe that an aggressive excisional approach is indicated for the venous anomalies that cause GI bleeding in BRBNS.

Association of Schatzki Ring With Eosinophilic Esophagitis in Children

Objective: To describe the clinicopathologic characteristics of children with Schatzki ring and to determine if Schatzki ring is associated with eosinophilic esophagitis. Methods: The authors report 18 adolescents with radiographically diagnosed Schatzki ring (SR). Their clinical and histologic characteristics were reviewed in a blinded fashion. Results: The mean age of the patients was 15.8 ± 0.8 years and mean duration of symptoms was 2.6 ± 0.4 years. By histologic criteria, two groups of patients were defined. Eight had clinical and histologic criteria of eosinophilic esophagitis (EE) and 10 of peptic esophagitis. There were no differences in the symptoms or radiographic findings in the two groups. The SR was not identified by endoscopy in any EE patient and was identified in 70% of peptic esophagitis patients. Grossly apparent mucosal features associated with EE were significantly more common in those with EE. Those with peptic esophagitis had a significantly higher acid exposure than did those with EE (12.6 ± 2.9 v 2.0 ± 1.1%; P < 0.01) by esophageal pH probe. Patients with peptic esophagitis responded to proton pump inhibitors and/or dilatation, whereas those with EE did not have good response and required specific therapy for EE. Conclusions: EE may play a role in the pathogenesis of some patients with SR.

Complications following percutaneous endoscopic gastrostomy and subsequent catheter replacement in children and young adults

BACKGROUND Percutaneous endoscopic gastrostomy has gained wide acceptance for patients who require prolonged tube feeding support. We sought to identify complications and associated risk factors of endoscopic gastrostomy and subsequent catheter replacement in pediatric patients. METHODS Medical records were reviewed for 137 patients. Odds ratios were calculated for complications related to patient age, weight, weight-for-age Z score, and principal diagnosis. RESULTS Seventeen patients (12.4%) developed significant complications after gastrostomy: cellulitis occurred in 10 patients (7.3%); other complications included gastrocolic fistula (2), duodenal hematoma (1), complicated pneumoperitoneum (1), necrotizing fasciitis (1), gastric perforation (1), and catheter migration (1). Patients with cancer had significantly greater odds for developing a wound infection, and patients with AIDS had significantly greater odds for total complications. A trend toward increased wound infection was observed in patients with cardiac disease. Age, weight, and weight-for-age Z score were not associated with adverse outcome. Two complications occurred in 85 patients (2.4%) after gastrostomy catheter replacement. CONCLUSIONS Pediatric patients with cancer and AIDS are at increased risk for complications after endoscopic gastrostomy regardless of age, weight, or nutritional status. Infrequent yet life-threatening complications may occur after replacement of initial gastrostomy catheter.

GASTROINTESTINAL BLEEDING IN INFANCY AND CHILDHOOD

Gastrointestinal (GI) bleeding is an alarming problem in children. Although many causes of GI bleeding are common to children and adults, the frequency of specific causes differs greatly, and some lesions, such as necrotizing enterocolitis or allergic colitis, are unique to children. This article reviews the spectrum of GI bleeding in infants and children. The causes, diagnostic evaluation, and management are discussed, and differences with adult medicine are highlighted.

Endoscopic placement of the capsule endoscope in children

BACKGROUND Capsule endoscopy provides a minimally invasive examination of the entire small bowel. However, some children and disabled adults may be unable to independently ingest the capsule. A new method for endoscopic placement of the capsule endoscope is described. METHODS Consecutive children who required capsule endoscopy of the small bowel and who were unable to independently ingest the capsule were selected for endoscopic placement. A net retrieval catheter and a translucent ligation adaptor were used to hold and stabilize alignment of the capsule during endoscopic insertion into the distal duodenum. RESULTS Eleven pediatric patients underwent successful endoscopic placement of a capsule endoscope in the duodenum without complication. One capsule migrated back into the stomach, where it remained for the life of the battery. CONCLUSIONS Endoscopic placement of the capsule endoscope by using the described technique appears to be effective and safe. It facilitates capsule endoscopy in patients who are unable to independently ingest the capsule.