AN UNUSUAL CAUSE OF POST-FUNDOPLICATION EMESIS©
Adam Mezoff, David Hitch, Sonia Michail, Daniel PreudHomme, Department of Pediatric GI & Nutrition, Wright State University School of Medicine, Dayton, OH; Department of Surgery, Childrens Medical Center, Dayton, OH
A 7-year-old developmentally delayed male presented for evaluation of a 4 month history of increasing vomiting and 5 pound weight loss. Emesis now occurred after each meal, while previously a regular diet was tolerated. The patient was a former 26 week premature infant with IVH who underwent fundoplication because of difficulties with GER. Developmentally the patient was non-ambulatory and nonverbal. Physical exam showed a thin microcephalic male whose abdominal exam was only remarkable for scars from previous surgery. Neurologically the patient had spastic quadriplegia. Initial laboratory studies included normal electrolytes, complete blood count, and urinalysis. Upper gastrointestinal series demonstrated a rounded soft tissue defect in the esophagus consistent with a polyp or leiomyoma. There was no obstruction to the passage of barium, although some esophageal dilation was noted. Upper gastrointestinal endoscopy showed a large trichobezoar in the lower esophagus. Immediately superior to the LES; several polypoid lesions of the mucosa were noted `bunched together'. A small suture protruded from the base of one of these lesions and was firmly attached to the bezoar. The suture was cut between mucosa and bezoar, and the bezoar was then removed. The remaining portion of the suture retracted into the esophageal mucosa. The patient was discharged home in good condition after his procedure, and mother was contacted 72 hours after discharge. She stated that the patient's symptoms had completely resolved. Upon further questioning, she stated the patient frequently played with the two family dogs (longhaired) and often put non-nutritional objects in his mouth. Our patient had the inadvertent placement of a suture through the esophageal mucosa at the time of his fundoplication. Hair that was likely ingested while playing with the family dogs became tangled around this suture and with time, the increasing accumulation of hair led to the formation of a large bezoar. The bezoar created a ball-valve effect in the esophagus, with subsequent vomiting. Removal of the bezoar led to immediate relief of the patient's symptoms. This case demonstrates a previously unreported late occurring complication of fundoplication leading to vomiting.
INTRALUMINAL IMPEDANCE IN PATIENTS WITH GASTROESOPHAGEAL REFLUX (GER) AND RESPIRATORY (R) OR EAR, NOSE, THROAT (ENT) SYMPTOMS
Vasundhara Tolia, Anne Wuerth, Kim Boyer, Pediatric Gastroenterology, Children's Hospital of Michigan, Detroit, MI, USA
There has been a lot of interest in the role of GER in patients with chronic ENT and R diseases. It is possible that even non-acidic reflux may injure these organs. Such non-acid reflux would not be detected by routine pH monitoring, so we performed a prospective study to evaluate the occurance of acidic and non-acidic reflux using MII in children between 6–15 years of age with proven GER on endoscopy and having chronic R and/or ENT symptoms. All patients had discontinued any prokinetic or acid suppressor treatment for at least 3 days prior to the study. MII catheter with 6 rings and 2 pH sensors were introduced intranasally and the distal pH electrode was placed 3 cm above GE junction and confirmed radiologically after over-night fast. They ate a regular meal and laid down on the right lateral side for 4 hours with continuous monitoring. Another meal was given after 4 hours and MII was continued in upright position for 2 additional hours. The tracings were reviewed for all retrograde peristalsis episodes starting from distal esophagus, the uppermost level of the refluxate (low, mid or high esophagus), its clearance time in minutes (clearance of the episode was the time until impedance reaches level denoting MII reflux event), and the pH of refluxate at the distal & proximal sensors.
5 patients (2F, 3M), mean age 12.2 years were evaluated. Four had both R and ENT symptoms and one had R symptoms only. Analysis for 2 post prandial hours in both positions is shown in the table.
Number of reflux episodes was not different during the 2 post prandial hours in either position. The majority of acid refluxate did not reach the proximal sensor where pH remained > 4.0. Further studies are needed in children with GER and supraesophageal symptoms using MII.
RUMINATION BEHAVIOR IN NEUROLOGICALLY NORMAL PRE-ADOLESCENT MALES
John F Pohl, Michael Mirzai, Jeremy Gibson, Pediatric Gastroenterology, Scott and White Hospital (Texas A&M HSC), Temple, TX; Pediatric Psychiatry, Scott and White Hospital (Texas A&M HSC), Temple, TX; Pediatrics, Scott and White Hospital (Texas A&M HSC), Temple, TX
Rumination disorder as defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM IV-TR) is repeated regurgitation and rechewing of food for a period of at least 1 month following a period of normal functioning. This behavior is not due to gastroesophageal reflux, is not exclusively present in eating disorders, and has a high prevalence in mentally handicapped children. Few studies have described this condition in neurologically normal children, especially males. We describe two healthy pre-adolescent male children (6 years and 11 years old) who presented to our institution with behavior consistent with rumination syndrome. These children had a history of effortless vomiting for at least one year. Neither patient had a history of an eating disorder. Both patients had recent psychosocial stressors and had normal complete blood counts, serum electrolytes, liver function tests, and upper gastrointestinal series. Upper endoscopy revealed esophagitis in one patient. A 24-hour pH probe study performed on each child was consistent with rumination. Specifically, a significant decrease in esophageal pH was noted during awake periods while negligible changes were present during sleep. Both patients were referred to pediatric psychology, and counseling led to decreased emesis episodes and eventual symptom resolution. In summary, rumination syndrome can occur in neurologically normal males. A search for psychological stressors is essential when evaluating these patients. The use of the 24-hour esophageal pH probe is a helpful study when evaluating for rumination syndrome in these otherwise healthy children.
CRICOPHARYNGEAL ACHALASIA (CPA): A RARE BUT NOTEWORTHY CAUSE OF FAILURE TO THRIVE
Allan I Tschernia, Suzanne Abraham, Mount Sinai School of Medicine, New York, NY, Albert Einstein College of Medicine, Bronx, NY
CPA is a rare but significant cause of swallowing disorder in pediatrics, either idiopathic or as part of neuro-muscular illness. The former presents a diagnostic dilemma as it may occur in an otherwise healthy youngster. We report the case of a male infant born full term without perinatal complications, referred at 2 months of age for evaluation of failure to thrive. A review of the patient's growth data revealed a drop from the 75% to 25% in weight/age. Height and head circumference were sparred. Patient was breastfeeding, described as constantly hungry with loose stools. Mother did report a chief complaint of noisy feeding, without wheezing, choking or gagging. The infant was reported as healthy without recurrent pneumonia or otitis media. A complete blood count, standard chemistries and sweat test were within expected range for age. A barium swallow was reported as normal. Neurological and ENT evaluations were all within normal limits. Head, neck and thoracic MRI showed no evidence of structural anomalies.Upper gastrointestinal endoscopy performed under general anesthesia revealed a narrowed though not stenotic pharyngoesophageal (PE) segment; biopsies were unremarkable. The patient underwent a comprehensive video-fluoroscopic swallowing assessment. Data were consistent with CPA, with absent or near incomplete opening of the PE segment and obstruction to partial or complete bolus flow at the level of C2–C3, with rapid retrograde movement of residual bolus. A jet effect was observed secondary to the severity of the luminal narrowing. Airway contamination occurred as a result of post-swallow pharyngeal residua penetrating the laryngeal vestibule. The patient was maintained on tube feedings and achieved catch-up growth by 4 months of age along with age-appropriate neuro-cognitive development. Review of the literature on CPA suggests a late diagnosis with significant growth compromise. Close collaboration with feeding/motility specialists should allow for earlier diagnosis and intervention. Additionally general information regarding feeding and motility disorders should be made available to the general practitioner.
HERPES SIMPLEX ULCERATIVE ESOPHAGITIS IN HEALTHY CHILDREN
Abdurahman Alhussaini, J Decker Butzner, James D Kellner, Marli A Robertson, Department of Pediatrics, Alberta Children's Hospital and University of Calgary, Calgary, AB, Canada
Herpes simplex virus (HSV) is a common cause of ulcerative esophagitis in the immunocompromised or debilitated host. This condition is considered to occur very rarely in otherwise healthy children. We report three cases of HSV esophagitis in apparently immunocompetent children, two of whom had no herpetic lesions on the lips nor oropharynx.
A healthy 16 year old male presented with odynophagia and fever for 3 days. He had no skin, lip nor oropharyngeal lesions. Endoscopy revealed multiple discrete ulcers with erythema in the upper esophagus and extensive confluent ulceration with necrotic exudate in the lower half of the esophagus. The patient improved over 72 hours on acid suppression. The histology showed acute inflammation and intranuclear inclusions. Immunoperoxidase-staining and viral cultures confirmed HSV-1 infection.
A 3 year old girl, who had been diagnosed with nutcracker esophagus at age 18 months with complete resolution of symptoms for the past year, presented with acute onset of odynophagia, retrosternal pain and fever. She had refused food and fluid for 6 days. There were no skin, lip nor oropharyngeal lesions but her father had a “cold sore”. Upper endoscopy revealed multiple, discrete, small diameter, well circumscribed ulcers from the mid to lower esophagus. Biopsies showed intranuclear viral inclusions and immunoperoxidase-staining was positive for HSV. The patient was able to tolerate a soft diet 48 hours after starting intravenous acyclovir.
A 16 year old male presented with 4 days of severe odynophagia and fever associated with a probable HSV lesion on his lip. He was treated with acyclovir for 36 hours before endoscopy. Endoscopy findings were typical for HSV esophagitis although the histology and immunostaining were negative, probably because of the preceding antiviral treatment. Testing revealed no evidence of immunodeficiency, including negative serology for human immunodeficiency virus.
Although uncommonly reported in the normal host, HSV esophagitis should be considered in any child presenting with odynophagia, even in the absence of skin or oropharyngeal lesions.
MULTICHANNEL INTRALUMINAL IMPEDANCE (MII): A SESITIVE TECHNIQUE TO REDEFINE GASTROESOPHAGEAL REFLUX (GER) IN CHILDREN
Hayat M Mousa, Radu Tutuian, Pediatric Gastroenterology, Ohio State UniversityColumbus Children Hospital, Columbus, OH; Medicine, Medical University of South Carolina, Charleston, SC
The basic principle of MII technique is to record the changes in electrical impedance in the gastrointestinal lumen caused by the passage of a bolus. MII monitoring offers a better understanding of GER and clearance of refluxate. Several studies have been devoted to acid clearance, but clearance of nonacid reflux has received less attention.
1) Compare the sensitivity of MII technique to pH monitoring in detecting GER. 2) Use MII technique to investigate the possible effect of refluxate pH on the height and clearance of reflux.
Combined pH and MII catheter was used in 2 infants age 4 and 6 wks referred for irregular breathing patterns, desaturation and perioral cyanosis without clinical symptoms of GER. Both had negative conventional pH monitoring. MII catheter was placed with the pH probe at 2.5 cm above LES and 8 adjacent electrodes.
During 2466 minutes of impedance recording, 188 MII-GER events occurred, 24/188 with acid GER, making conventional pH monitoring sensitive only to 13% of total measured reflux episodes. Linear regression models were used to assess the relationship between the pH levels, bolus contact time (BCT) at each site and maximum height, (where maximum height is the most proximal channel at which BCT was > 2 sec). The statistically significant findings: 1) As Nadir pH increases by one point the Z1 duration increases by 0.75 second. 2) As the Nadir pH increases by 1 point the height increases by 0.94 cm. 3) As the delta increases by 1 point, the height decreases by 1.07 cm. Differences in the distribution of the proportion of acid across the height were tested using Chi-square tests. The correlation between Nadir pH and delta pH was estimated using Spearmans correlation. The correlation is–0.226 (p-value = 0.077) for patient 1, and –0.649 (p-value < 0.001) for patient 2.
1.In relation to the overall reflux events detected by MII, pH monitoring demonstrate a very low sensitivity toward detecting GER. 2.Being independent of pH, impedance monitoring can identify broader range of reflux episodes. 3.The height reached by GER is proportionally increased with higher pH. 4.Bolus contact time at proximal esophagus significantly increases as nadir pH value increases. 5) GER associated with higher changes in pH from baseline has a shorter BCT and better clearance.
A SUBSET OF CHILDREN WITH REFRACTORY ALLERGIC EOSINOPHILIC ESOPHAGITIS ARE RESISTANT TO SWALLOWED FLUTICASONE PROPRIONATE
Richard J Noel, Philip E Putnam, Margaret H Collins, Amal H Assa'ad, Marc E Rothenberg, Division of Gastroenterology, Hepatology, and Nutrition; Division of Pathology; Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
Eosinophilic esophagitis (EE), an inflammatory disorder with a spectrum of clinical presentations, seems to be increasing in frequency. Although the etiology is unknown, allergic and non-allergic subtypes are distinguishable by the response to dietary management. Skin-prick (SPT), RAST, or skin-patch testing against food antigens may identify foods to which the child is sensitized, but it is not clear whether compulsive elimination of implicated foods from the diet leads to resolution of EE. This study examines the therapeutic response to swallowed fluticasone proprionate (FP) in children with non-allergic EE and allergic EE refractory to elimination diet. Methods: For this retrospective analysis, 20 children with EE were identified by characteristic symptoms, furrowing and thickening of the esophageal mucosa at endoscopy, and esophageal biopsies with eosinophil-predominant inflammation (peak eosinophil density of 24 per 400x microscopic field) and marked basal cell layer hyperplasia. Ten patients were considered non-allergic, based on negative SPT against an extended panel of >40 foods, and they remained on a regular diet. Ten patients were identified who had positive SPT but failed to respond to at least 3 months of dietary elimination of those antigens, as confirmed by repeat endoscopy with biopsy. Both groups received aerosolized FP by metered dose inhaler, swallowed instead of inhaled, with no change in diet. Follow-up clinical assessment and endoscopy with biopsies were performed after at least three months of FP. Biopsies from one patient treated with systemic steroids were included for comparison. Average time on therapy between assessments was 4.8 months. Results: Symptomatic, endoscopic, and histologic resolution of the EE was demonstrated in 15/20 patients (75%) treated with FP, and was similar to the improvement seen with systemic steroid therapy. Notably, EE in 5 of the 10 allergic children did not resolve (2 unchanged, 3 partial improvement; p=0.03). The only adverse effect of FP was the development of candidal esophagitis in 4 patients. Conclusion: Swallowed fluticasone is highly effective in the majority of patients with EE, however, children with a refractory allergic subtype appear to be less sensitive to this therapy.
ABNORMALITIES IN ESOPHAGEAL BODY CONTRACTIONS ARE ASSOCIATED WITH GASTROESOPHAGEAL-REFLUX DISEASE IN CHILDREN
Denesh K Chitkara, Christine Fortunato, Samuel Nurko, Motility Unit, Division of Gastroenterology and Nutrition, Children's Hospital Boston, Boston, MA
Motor abnormalities of the esophageal body contribute to impaired clearance of refluxed gastric acid. However, it is unclear whether abnormal esophageal body contractions are the cause or consequence of peptic esophagitis.
To evaluate esophageal body motor activity that occurs during GER in pediatric patients.
Esophageal motor activity was measured by 24 hour pH/manometry with a solid state probe containing 4 pressure transducers, and 1 pH electrode positioned 3 cm above the LES. Patients were classified in 3 groups: Group C (controls) (normal pH probe, normal biopsy and manometry, no dysphagia), Group 1 (abnormal pH probe, normal biopsy),and Group 2 (abnormal pH probe with esophagitis). Esophageal motor events were analyzed for each reflux episode, and for 30 seconds before (PRE) and 4 minutes after (POST). Results were compared between groups, and expressed as mean ± SE.
Nineteen patients were studied, and their manometric characteristics are shown in the table below. Group 1 and 2 had significantly fewer contractions per minute PRE, during, and POST GER. Group 1 showed a higher % of contractions > 180 mmHg during the reflux events.
Patients with GERD have fewer esophageal body contractions/minute associated with GER which may be responsible for delayed acid clearance. Esophageal motor abnormalities in those children with GERD without esophagitis support the notion that GERD in children may be related to primary motor abnormalities of the esophagus.
CORRLEATION BETWEEN NUMBER OF EOSINOPHILS AND REFLUX INDEX ON SAME DAY ESOPHAGEAL BIOPSY AND 24 HOUR ESOPHAGEAL PH PROBE
Steven J Steiner, Sandeep K Gupta, Joseph M Croffie, Joseph F Fitzgerald,
The presence of eosinophils on esophageal biopsy has been noted as a marker of esophagitis in children. Previously, the presence of denser infiltrates of eosinophils in the esophageal epithelium was thought to be a marker of more severe gastroesophageal reflux. More recently, the presence of eosinophilic inflammation without evidence of gastroesophageal reflux has led to the new diagnosis of eosinophilic, or allergic, esophagitis. The aim of this study was to correlate the number of eosinophils on esophageal biopsy with reflux index on same day 24 hour esophageal pH probe study.
A retrospective analysis of data collected from patients between one and eighteen years of age from January 2000–March 2002 was performed. Patients were eligible if they underwent endoscopy with esophageal biopsies and 24 hour esophageal pH probe on the same day. Patients were excluded if they had prior endoscopy at our institution or if they had undergone anti-reflux surgery. The patients were divided into four groups based on maximum number of eosinophils in esophageal biopsy and other histologic change (i.e. vascular papillae elongation and basal cell hyperplasia) noted on esophageal biopsy: Group 1: 0 eosinophils/hpf and no histologic change, Group 2: 0 eosinophils/hpf but histologic change, Group 3 1–5 eosinophils/hpf and histologic change, and Group 4: >5 eosinophils/hpf and histologic change. Reflux indices were then analyzed within each group.
One hundred and eighty-seven patients met the inclusion criteria. The mean reflux indices (+/− standard deviation) in each group were Group 1: 1.80 (+/− 1.94), Group 2: 4.35 (+/− 10.3), Group 3: 6.76 (+/− 11.9), and Group 4: 2.78 (+/− 4.21). The mean reflux index in Group 3 was significantly different (p<0.05) than all other groups using non-parametric analysis. There was no significant difference between Groups 1,2, and 4.
The presence of denser infiltrates of eosinophils does not correlate with increased gastroesophageal reflux. In fact, the presence of more than five eosinophils/hpf is likely associated with a normal reflux index and a non-acid related cause of esophagitis.
COMPARISON OF GASTROESOPHAGEAL REFLUX (GER) SYMPTOMS AND FEATURES IN CAUCASIAN (CC) AND AFRICAN AMERICAN (AA) ADOLESCENTS
Priyadarsini Ramesh, T S Gunasekaran, Fangxi Zhou, Pediadric Gastroenterology, Lutheran General Children's Hospital, Park Ridge, IL; Pediadric Gastroenterology, Lutheran General/Ronald McDonald Children's Hospital, Park Ridge, IL; Advocate Research and Education, Lutheran General Hospital, Park Ridge, IL
To determine the prevalence of GER symptoms in CC and AA adolescents and see if there is a difference in the presenting symptoms, proposed risk factors, and treatment.
A comprehensive questionnaire was distributed in 3 high schools, age 14–18 yr., inquiring demographics, esophageal symptoms (ES); heartburn, regurgitation and dysphagia, respiratory symptoms (RS); wheezing, shortness of breath and cough, chronic respiratory disorders, risk factors - smoking,alcohol and caffeine use, and medications used. Symptoms were defined significant when reported as occuring at least once a month in the past year prior to completion of the survey.
Total students surveyed were 1743. CC 591 (34%), AA 574 (33%)and others 578 (23%). Prevalence of ES in CC males 64% and females 34%, AA males 45% and females 49%. A comparison of rest of the features is shown in the table.
Prevalence of ES of GER was higher in CC (44%), than A A adolescents (34%), more in CC males (64%) than females but almost equal in both sexes in AA. More than half of students with ES in both races also had RS. The percentage of students with asthma and with ES were more in CC than AA. Smoking, alcohol and caffeine use was more in CC and the first two were found to be risk factors in both races but not caffeine.Medications used for ES was slightly more in CC than in AA. Students of both races who consulted a physician for ES was < 1%.
IMMUNOLOGIC DIVERSITY OF PEDIATRIC ESOPHAGITIS
Fiona Rubenstein, Marta Vielhaber, Alton Melton, Maya Srivastava, Pediatrics, MetroHealth Medical Center, Cleveland, OH; Allergy and Immunology, Cleveland Clinic, Cleveland, OH
Esophagitis in children has classically been characterized as reflux-related or allergic, both characterized by infiltration of eosinophils into the mucosa. In adults, recent evidence suggests that esophagitis may have a diverse immunologic pathogenesis. Purpose: This study characterized the cytokines present in the esophageal mucosa of pediatric patients with esophagitis, to determine if despite similar histopathology, underlying mechanisms of disease were different. Methods: Biopsies approximately 3 cm above the gastroesophgeal junction were obtained during routine upper endoscopy from 22 patients age 2–18 years. Histopathology revealed 13/22 with normal/mild and 9/22 with moderate to severe esophagitis. Biopsy tissue was placed in lysis buffer RLT and β-mercaptoethanol, homogenized, and RNA isolated using Qiagen RNAeasy kit. Potential DNA contamination was removed via DNAase 1 and RNase Inhibitor, followed by heating. Total RNA underwent reverse transcription to produce cDNA using Superscript II. PCR amplification of cDNA to 40 cycles was performed with Taq polymerase and primers for GADPH, eotaxin, RANTES, IL-5, IL-16, IL-8, TNF-α, GM-CSF, TGF-β1, IL-18, nad IFN-γ. After addition of stop solution, PCR product was loaded onto 2% agarose gels, followed by electrophoresis, stained with ethidium bromide, examined under uv transillumination, and photographed. Results: In the moderate/severe vs the normal/mild group,eotaxin mRNA was detected in 71% vs 54%; TNF-α (67% vs 31%), IFN-γ (14% vs 0%), TGF-β1 (33% vs 0%), IL-16 (67% vs 4%), IL-8 (29% vs 44 %), IL-18 (40% vs 67%). RANTES (71% vs 80%) was detected frequently in both groups, possibly due to constitutive expression by epithelia. GM-CSF was not detected. IL-5 was detected only in three patients, all of whom had significant peripheral eosinophilia. Conclusions: A greater number of cytokines were expressed in moderate to severe esophagitis compared to normal/mild. The immunologic profile was not homogeneous, despite similar histologic severity, and may reflect differences in the systemic immune reponse. Further studies to identify cellular sources of these cytokine transcripts and to determine protein expression are warranted.
HUMAN β-DEFENSIN 1 (hBD1) AND 2 (hBD2) AND α-DEFENSIN 5 (HD5) AND 6 (HD6) EXPRESSION IN PEDIATRIC ESOPHAGEAL DISEASES
Marta M Vielhaber, Fiona Rubenstein, Alton Melton, Maya D Srivastava, Allergy and Immunology, Cleveland Clinic, Cleveland, OH; Pediatrics, MetroHealth Medical Center, Cleveland, OH
Defensins are small antimicrobial peptides of the innate immune system that can also modify the adaptive immune reponse. Defensin expression in pediatric esophageal disorders has not been previously described. Purpose: This study evaluated the expression of hBD1, hBD2, HD5, and HD6 in pediatric patients (23 months to 18 years) with eosinophilic esophagitis, Barrett's esophagus, Crohn's disease, reflux, and controls (normal histology). Specimens (n=26) obtained during routine endoscopy from 3 cm above the gastroesophageal junction underwent RNA extraction using Qiagen RNAEasy kit, treatment with DNAse 1 and RNAse inhibitor followed by heating, and reverse transcription with Superscript II. Resulting cDNA underwent PCR to 40 cycles using Taq polymerase and primers designed using http://www.ncbi.nlm.nih.gov and Primer 3 program (expected products 200 bp). After adding stop solution, product was loaded onto 2 % agarose gels, followed by electrophoresis, stained with ethidium bromide, examined under uv light and photographed. Results: hBD1 RNA was detected in 5/6 patients wih normal esophageal histology, and 17/19 patients with esophagitis. The 3 hBD1 negative patients had systemic immunologic disorders (JRA, Bechet's, chronic diarrhea with high ESR). hBD2 RNA was detected in 16/19 patients (84%) with esophagitis. The 6 patients hBD2 negative included 2 normal controls, the patient with Bechet's (normal esophageal histology), a child with Celiac disease and moderate esophagitis, the patient with diarrhea/high ESR, and the most severe esophagitis case. HD6 was not detected, HD5 was detected in 1 patient only who had IDDM. Conclusions: hBD1 mRNA is present in the esophageal mucosa of most normal children and in esophagitis. hBD2, known to be regulated by NFKB, may be more frequently found in the inflamed esophagus. No clear pattern of defensin expression was associated with a specific disease type. More studies on the role of defensins in these diseases are needed.
ALTERNATIVE METHODS OF LANSOPRAZOLE ADMINISTRATION
Sandeep K Gupta, Yi-Lin Chiu, Roberta G Keith, Joseph F Fitzgerald, Riley Children's Hospital; Indiana Univ School of Medicine, Indianapolis, IN, Abbott Laboratories, Abbott Park, IL, TAP Pharmaceutical Products Inc., Lake Forest, IL, Riley Children's Hospital; Indiana Univ School of Medicine, Indianapolis, IN
To compare the bioavailability of alternative methods of lansoprazole administration with that of the intact capsule. Previous studies have shown the pharmacokinetics of lansoprazole to be similar between adults and children (1–17 yrs).
Five randomized, crossover studies were performed in healthy adults. Treatment arms were single-dose with at least a 7-day wash-out period between them. Methods included oral ingestion of strawberry suspension; capsule granules sprinkled on 1 tablespoon of yogurt, pudding, cottage cheese, applesauce or strained pears; granules mixed in 60 mL of orange juice or tomato juice; and granules mixed in apple juice (40 mL) and administered through a NG tube. Blood samples were obtained over 12 hours post-dose to determine the area under the concentration vs. time curve (AUC). Relative bioavailability of each alternative method of administration compared to the 30-mg intact capsule was assessed by the two 1-sided tests procedure using a 90% confidence interval (CI).
The 90% CIs for the AUC of the alternative methods of administration were all within the acceptable equivalence range of 0.80 to 1.25.
These results indicate similar bioavailabilities in healthy adults among lansoprazole administered as suspension, as granules sprinkled on various soft foods or mixed in juice, administered through a nasogastric tube, or as an intact capsule. These alternatives may be useful when dosing patients who have difficulty swallowing the intact capsule. Funded by TAP.
IS SCHATZKI RING ASSOCIATED WITH EOSINOPHILIC ESOPHAGITIS?
Samuel Nurko, Khaled Husain, Jonathan Teitelbaum, Kamran Badizadegan, Victor Fox, Don Antonioli, Carlo Buonomo, Christine Fortunato, Glenn Furuta, Division of Gastroenterology, Pathology, and Radiology, Children's Hospital Boston, Boston, MA
The physiopathology of Schatzki ring (SR) is not well understood. It has been associated with hiatal hernia and peptic esophagitis (PE), although our recent experience suggests that some patients may have eosinophilic esophagitis (EE).
Identify the clinicopathological features of patients with SR.
Retrospective analysis of the characteristics of children with SR. Validated radiographic criteria were used to diagnose SR. All clinical and histopathologic analysis were done blindly. Patients were classified as either having PE or EE using published criteria.
Eighteen patients with SR were identified. Clinicopathologic evidence of EE was found in 8/18.
Patients with PE responded better to anti-GER treatment and/or dilatation than those with EE.
This is the first report that describes the association between EE and SR. Neither symptoms nor UGI allow clinical distinction between PE and EE. Mucosal biopsy of patients with SR is critical to make the correct diagnosis. EE may play a role in the pathogenesis of SR.
FAMILIAL SCHATZKI'S RING: CASE REPORT EMPHASIZING THE ETIOLOGIC CONSIDERATIONS
James R Rick, Mark J Cossentino, Frank M Moses, Pediatrics, Walter Reed Army Medical Center, Washington, DC; Gastroenterology, Walter Reed Army Medical Center, Washington, DC
Schatzki's ring is uncommon in children and adolescents. It typically causes varying degrees of solid food dysphagia and the etiology is unknown. Congenital origin, pill impaction, result of mucosal plication, and sequela of gastroesophageal reflux disease (GERD) are possible factors involved in either ring formation or progression. Positive family history is not previously reported. We report Schatzki's ring spanning two generations associated with reflux esophagitis.
A 16 yr old white male was referred for the evaluation of chronic, intermittent dysphagia. Symptoms began at age 5 and currently he describes 1 to 2 episodes per month of solid food dysphagia relieved by inducing vomiting or drinking liquids. He is asymptomatic between episodes and denies heartburn, vomiting, weight loss, coughing, choking, and odynophagia. He takes no medications and has no food allergies or asthma. His mother and sister deny gastrointestinal complaints. His father, age 46, has a long history of GERD symptoms and dysphagia. Upper endoscopy of his father showed a Schatzki's ring with a 1 cm pink mucosal tongue, hiatal hernia, and biopsies of the distal esophagus revealed reflux esophagitis as well as columnar mucosa without specialized intestinal metaplasia. Also, his paternal grandfather and great-grandfather suffered from dysphagia and GERD that required serial esophageal dilations. The patient weighed 64 kg (50%) and his height was 181 cm (75%). Vital signs, physical exam, and observation of swallowing were normal. Results of a barium swallow included normal esophageal caliber, motility and contour; however, at the gastroesophageal junction there was a ring like constriction delaying the passage of 12 mm barium pill. Upper endoscopy demonstrated a membranous annular constriction at the squamocolumnar junction (Schatzki's ring) and a hiatal hernia. There was mild distal non-erosive esophageal findings and the Olympus GIF-100 (outer diameter 9.5 mm) passed easily. Distal esophageal biopsies were consistent with moderate reflux esophagitis. Treatment with rabeprazole 20 mg twice a day was instituted and possible dilation is planned during summer break. No episodes of dysphagia have occurred since the endoscopy 3 months ago.
We report the first known case of familial Schatzki's ring. Father and son involvement is well documented and other generations are possibly affected. In selected cases, Schatzki's ring maybe an inherited disorder. Alternatively, a genetic susceptibility for lower esophageal mucosal rings may result in faster disease progression and earlier clinical manifestations. The presence of GERD in this kindred with familial Schatzki's ring likely facilitated disease progression secondary to inflammation and/or esophageal narrowing.
A COMPARISON OF SEQUENTIAL ESOPHAGEAL HISTOLOGIC AND ENDOSCOPIC FINDINGS BEFORE & AFTER ANTI-REFLUX SURGERY OR PHARMACOTHERAPY IN PATIENTS WITH GASTROESOPHAGEAL REFLUX DISEASE
Ruba A Abdelhadi, Raja Rabah, Michael D Klein, Vasundhara Tolia, Pediatric Gastroenterology, Children's Hospital of Michigan, Detroit, MI; Pediatric Pathology, Children's Hospital of Michigan, Detroit, MI; Pediatric Surgery, Children's Hospital of Michigan, Detroit, MI
A review of the symptomatic, endoscopic and histologic findings in children with gastroesophageal reflux disease was performed to compare the outcome before and after surgical fundoplication (FP) versus medical treatment with proton pump inhibitors.
25 patients with GERD (16 M/ 9 F, mean age 10 ± 6 yrs) needing FP had been evaluated by endoscopy & biopsy before and after surgery; and 12 patients with GERD (9 M/ 3 F, age 10 ± 4 yrs) on chronic pharmacotherapy were reviewed. Endoscopic findings were graded using Savary-Miller criteria. Histology was evaluated blindly by the pathologist who was not aware of the type of treatment or timing of endoscopy. Mean duration of post-op follow-up endoscopy was 6 months (range, 3 mo–5 yrs) and after pharmacotherapy was 5 months (range, 3 mo–4 yrs). All data were converted to a numerical scale; SPSS version 10.0 was used for statistical analysis.
Pre & post-medical and surgical treatment findings did not reveal significant difference between the two treatment groups. Associated diseases present in surgical group were developmental delay-12 all of which relapsed after surgery, hiatal hernia-8, improved, asthma-5, improved. At post-op endoscopy, FP wrap was intact in 21/25 patients and patulous in 4. Reflux symptoms were controlled in 40% post-op compared to 70% with medical treatment.
Overall, there was dramatic improvement in esophagitis in patients undergoing FP compared to pharmacotherapy, though short lasting, as 60% relapsed after a mean period of 18 months following FP requiring re-institution of medical treatment with good response. Improvement following medical treatment was less dramatic, but longer lasting.
ARE THE MANOMETRIC FINDINGS IN PEDIATRIC ACHALASIA SIMILAR TO THOSE FOUND IN ADULTS?
Claudio Morera, Victor Fox, Domingo Jaen, Elena Pestana, Rosalba Caruso, Hector Azcarte, Samuel Nurko, Department of Gastroenterology, General Del Oeste, Caracas, Venezuela; Motility Unit. Division of Gastroenterology, Children's Hospital Boston, Boston, MA, USA
Achalasia is the most common esophageal motor disorder in children. Even though the manometric characteristics in adults have been well described, the information in children is limited.
Describe the manometric findings in children with achalasia.
The manometric tracings of 29 children with achalasia were reviewed. Achalasia was diagnosed when there were caharacteristic symptoms and an abnormal barium study together with absent peristalsis in the esophageal manometry. Values are reported as mean ± SE or percentages.
The mean age at presentation was 11.45 ± 0.95 years. The duration of the symptoms was 12.9 ± 3–3 months. There were a total of 362 swallows (90 dry and 272 wet). The LES has a mean pressure of 35.3 ± 1.2 mmHg. It was hypertensive in 49%. Those children with a hypertensive sphincter had a significantly longer duration of symptoms (19.8 ± 5.7 vs. 5.8 ± 0.9 months; p=0.03). In 4/29 (13.8%) patients there was no LES relaxation. In the other 25, there was some LES relaxation in 76.8% of swallows, with a mean percent relaxation of 66.4 ± 1.8. The residual pressure was higher after dry swallows (20.3 ± 2.3 vs. 14.9 ± 1 mmHg; p=0.02). In only one patient all LES relaxations were normal. In the other 24 patients, there were 18% of swallows that had a normal percent relaxation, but 82% were abnormal. There were no differences in the % relaxation after wet swallows when comparing those with normal or high sphincter pressure. The esophageal body analysis confirmed there was no peristalsis. The esophago-gastric gradient was 4.7 ± 0.2 mmHg. There were tertiary contractions in 97% of swallows. The mean amplitude of the contractions was 22.4 ± 0.7 mmHg, with duration of 10.3± 0.3 sec. The UES had a mean pressure of 63.7 ± 3.1 mmHg and showed 100% relaxation.
A normotensive LES was found in 51% of children. Three out of 4 swallows produced some partial relaxation. Most swallows produced tertiary esophageal contractions, which were of low amplitude and long duration. These findings contrast with those that have been described in adults, and may be related to the fact that the evolution of the disease process may be of shorter duration in children.
INCIDENCE OF GASTROESOPHAGEAL REFLUX IN CHILDREN WITH CHRONIC COUGH AND WHEEZING UNRESPONSIVE TO INHALATION THERAPY UNDERGOING BRONCHOSCOPY
Sundeep Arora, Diana Kong, Mikhail Kazachkov, Shivinder Narwal, Department of Pediatrics, Division of Pediatric Gastroenterology, Maimonides Medical Center, Brooklyn, NY
Gastroesophageal reflux (GER) is implicated in the pathogenesis of chronic cough and wheezing. Incidence of GER in patients with unexplained cough and wheezing is unknown. Here we present our experience with ten patients who underwent bronchoscopy and double-probe pH monitoring for chronic pulmonary symptoms unresponsive to bronchodilator and steroid therapy.
Ten children in the age range of 5 months to 10 years who were receiving inhaled bronchodilators and steroids for symptoms suggestive of reactive airway disease for more than 6 weeks were selected. All these children underwent bronchoscopy under conscious sedation followed by pH probe placement.
Severe GER was seen in 7 of 10 children by pH probe monitoring. Bronchoscopic findings in these children revealed bronchomalacia, laryngomalacia, vocal cord paresis, erythematous vocal cords, vocal cord nodules and adenoidal hypertrophy. Hyperreactive bronchial mucosa and diffuse bronchitis was seen on bronchoscopy in 3 children without GER and were diagnosed with asthma. Significant clinical improvement was noted in all the children with GER after anti-reflux therapy was initiated.
Our results suggest that GER may play an important role in children with persistent respiratory symptoms. Bronchoscopy and pH monitoring should be strongly considered in those children who fail inhalation therapy. We recommend starting empirical anti-reflux therapy in these children where bronchoscopy and pH monitoring is not available.
DOES NOCTURNAL ACID BREAKTHROUGH OCCUR IN CHILDREN WITH REFLUX ESOPHAGITIS? (PRELIMINARY RESULTS)
Marian D Pfefferkorn, Joseph M Croffie, Jean P Molleston, Sandeep K Gupta, Joseph F Fitzgerald, Pediatric Gastroenterology/Hepatology/Nutrition, J. W. Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, IN
The aims of this study are to determine if nocturnal acid breakthrough (NAB) occurs in children with reflux esophagitis treated with a proton pump inhibitor (PPI) and to evaluate resolution of esophagitis following PPI therapy with or without ranitidine at bedtime.
Pediatric patients diagnosed with reflux esophagitis on endoscopy and 24-hour intraesophageal pH-metry were prospectively enrolled. Intraesophageal pH-metry was repeated after 2 weeks of therapy with omeprazole 1 mg/kg BID ac. Patients with NAB were randomized to receive ranitidine 4 mg/kg or placebo qHS in addition to omeprazole. Patients without NAB remained on omeprazole. Endoscopy (and esophageal pH-metry in patients with NAB) were repeated after 16 weeks of therapy.
Five patients, 10–12 years old, have completed the study. Four patients demonstrated NAB after 2 weeks of therapy and 2 were randomized to receive ranitidine. NAB persisted after 16 weeks of therapy in 3 patients, one of whom received ranitidine. The esophageal pH-metry data in one patient could not be retrieved due to mechanical malfunction. In spite of the presence of NAB, the reflux index remained normal in 4/4 patients after 2 weeks of therapy and in 2/3 patients after 16 weeks of therapy. Reflux symptoms, endoscopic and/or histologic esophagitis were improved after 16 weeks of therapy in four patients and remained unchanged in one patient (Table 1).
NAB occured in children treated with high-dose omeprazole but did not result in abnormal reflux indices. Omeprazole with or without ranitidine at bedtime results in improvement of esophagitis. A larger sample size will be needed to confirm these findings.
ENDOSCOPY AND ESOPHAGITIS IN CHILDREN WITH GASTROESOPHAGEAL REFLUX
Sudipta Misra, John Nixon, Departments of Pediatrics and Pathology, UIC College of Medicine at Peoria and Children's Hospital Of Illinois, Peoria, IL
Significance of endoscopic findings and biopsy results remain unclear in infants and children with gastroesophageal reflux (GER).
To correlate endoscopic and histopathologic findings in children undergoing evaluation for GER.
Children ( 0 to 18 years ) who underwent endoscopy between April 1998 and March 2001 for GER were eligible for inclusion. Only those evaluated and endoscoped by one of the authors (SM) were included to eliminate inter-observer bias. Charts of these patients were reviewed for retrospective data collection. Children with atypical, persistent and/or life threatening symptoms of GER underwent endoscopy as per clinical care map. Four quadrant biopsies were done in most children, 3–5 cm proximal to the lower esophageal sphincter. One pathologist (JN) evaluated all the biopsies.
In 36 months, 90 (11.5%) of 780 children evaluated for GER and/or vomiting at the Children's Hospital of Illinois at Peoria underwent endoscopy. Among these 90 children (56 male, average age 35.18 months, median 5.8 months), endoscopic features suggestive of esophagitis were documented in 39. Grade 1 esophagitis was found in 33, grade 2 in 3 and grade 3 in 3. Biopsies, done in 38/39, revealed esophagitis in 20 and normal histology in 18. Eighteen out of 51 children with normal endoscopy had microscopic esophagitis. This finding was more common in older children, 6/27 below 6 months and 12/24 above 6 months had microscopic esophagitis with normal endoscopic finding (p=<. 05). In individual subjects, changes suggestive of esophagitis were found in 1 out of 4 biopsy pieces in 13 children, 2 out of 4 in 8, 3 out of 4 pieces in 4 and in all the pieces in 8 subjects. Size of the largest piece in the biopsy specimen did not correlate with a positive diagnosis of esophagitis. Gastritis (n-12) was more common in older children (6/19 above 5 years versus 4/46 below 6 months) and was frequently associated with microscopic esophagitis.
Normal or mildly abnormal appearing esophageal mucosa is common in children with gastroesophageal reflux. Children older than 6 months are more likely to have normal appearing mucosa with microscopic esophagitis. Patchy distribution of lesions may result in sampling error leading to normal appearing biopsies from a macroscopically abnormal esophageal mucosa. Routine four quadrant esophageal biopsies are recommended, especially in those with grade 0 or 1 esophagitis.
DOES THE ENDOSCOPIC IMPRESSION OF “NORMAL” ACCURATELY PREDICT NORMAL HISTOLOGY IN THE ESOPHAGUS?
Mark Gilger, Craig Dietrich, Ben Gold, Pat De Garmo, William Klish, Larry Saripkin, Anne Griffths, Mel Heyman, Colin Rudolph, Mitch Shub, Eric Hassell, Pediatrics, Baylor College of Medicine, Houston, TX; Pediatric Gastroenterology, Hepatology and Nutrition, Baylor College of Medicine, Houston, TX; Pediatrics, Emory University School of Medicine, Atlanta, GA; Medicine, Oregon Health Science Center, Portland, OR; Pediatrics, Baylor College of Medicine, Houston, TX; Pediatrics, Emory University School of Medicine, Atlanta, GA; Pediatrics, Hospital for Sick Kids, Toronto, ON, Canada; Pediatrics, University of California at San Francisco School of Medicine, San Francisco, CA; Pediatrics, Medical College of Wisconsin, Milwaukee, WI; Pediatrics, Phoenix Children's Hospital, Phoenix, AZ; Pediatrics, British Columbia Children's Hospital, Vancouver, BC, Canada
The pediatric endoscopist often encounters intestinal mucosa that appears “normal”. If the mucosa looks normal, should a mucosal biopsy be taken to confirm the endoscopic impression?
To determine the accuracy of the endoscopic impression of “normal esophagus” vs. the actual histologic findings of the esophageal mucosa in children.
The PEDS-CORI (Pediatric Endoscopy Database System - Clinical Outcomes Research Initiative) database was queried to directly compare the endoscopic impression of “normal esophagus” with histologic findings. There are now 10 PEDS-CORI sites in North America. Only the database at Texas Childrens Hospital (TCH) includes pathology. Between September 11, 1999 and November 30, 2001, 1781 upper endoscopies were performed at TCH. Of these, 285 (16 %) had an endoscopic impression of “normal esophagus”. All of these procedures had histology available for comparison. RESULTS: Of the 285 procedures with an endoscopic impression of “normal esophagus”, 168 (59%) had the same histologic impression. Chi Square analysis was performed to compare the endoscopic impression vs. histology. The endoscopic impression “normal esophagus” did not predict “normal” histology (χ=16.81, p=.01 ).
The endoscopic impression of “normal” esophagus was accurate in only 59% of the cases. Although the eye of the endoscopist is often correct, biopsy of normal appearing mucosa should be routinely performed.
GASTROESOPHAGEAL REFLUX DISEASE (GER) QUESTIONNAIRE TO ASSESS QUALITY OF LIFE (QOL) IN PATIENTS AND PARENTS
V Tolia, L Essenmacher, K Boyer, J Ager, Department of Pediatrics-Outcomes Research, Wayne State University, Detroit, MI
A prospective study was conducted to assess QOL for patients diagnosed to have GERD on endoscopy and histology and their parents. The patients were between 2 – 18 years of age. An 11 page questionnaire was devised to assess demographics, symptoms and QOL issues.
The questionnaire with informed consent was given to parents after establishing diagnosis. 94 patients were given the questionnaire and 34 mailed these back. 28 patients were mailed the questionnaire again after receiving the first one to assess the test-retest reliability and 10 returned those.
The survey consists of symptoms grouped into 5 different categories: 1. Gastrrointestinal, 2. Ears, nose throat, 3. Respiratory, 4. Neurological and 5. Allergy. To develop scales for these symptoms we assessed the internal consistency of these symptom groups by assessing Crohnbachs Alpha for each group. The Crohnbachs Alpha for each set of symptoms with k items are: 1. Gastrointestinal= 0.87, k= 23, 2. Ears, nose, throat= 0.88, k=11, 3. Respiratory= 0.76, k=5, 4. Neurology=0.64, k=6, and 5. Allergy= 0.59, k=4. Alpha was also computed for the set of negative Quality of Life (QOL) questions for the child (Alpha= 0.96, k=30).
In addition, there were 10 completed second surveys returned between 2 –10 months after the first survey for which we assesed test-retest related reliability. The test-retest reliabilities were: Gastrointestinal= 0.92, Ears, nose, throat= 0.63, Respiratory= 0.92, Neurology= 0.67, Allergy= 0.99, childs QOL= 0.74. All except for the Ear, nose, throat scale were significant at the 0.05 level.
We also correlated the childs and parents QOL scales with the symptom scales for the 34 children. The correlations of the childs QOL scale with the Gastrointestinal, Ears, nose, throat, Respiratory, Neurological, and Allergy scales were 0.56, 0.55, 0.38, 0.68, and 0.54 respectively and with the parents QOL scale were 0.60, 0.63, 0.51, 0.72 and 0.59. All correlations were significant at the 0.05 level which indicates that as the any of these symptom scales increase and affect the children more, both the childs and parents quality of life are also affected negatively. Further studies are needed to understand the role of GERD in childrens and their parents lifetsyle.© 2002 Lippincott Williams & Wilkins, Inc.