Esophagitis in children and adults with cystic fibrosis

THE AMERICAN JOURNAL OF GASTROENTEROLOGY © 2002 by Am. Coll. of Gastroenterology Published by Elsevier Science Inc.

Vol. 97, No. 9, Suppl., 2002 ISSN 0002-9270/02/$22.00

Abstracts Submitted for the 67th Annual Scientific Meeting of the American College of Gastroenterology October 20 –23, 2002, Seattle, Washington

ESOPHAGUS 1 CHARACTERIZATION OF THE ABNORMALITY IN ESOPHAGEAL ACID EXPOSURE IN GASTROESOPHAGEAL REFLUX DISEASE Jerry D. Gardner*, Sheila Rodriguez–Stanley, Malcolm Robinson, Sheldon Sloan and Philip B. Miner, Jr. Science for Organizations, Inc, Chatham, NJ; The Oklahoma Foundation for Digestive Research, Oklahoma City, OK and Janssen Pharmaceutica, Titusville, NJ. Purpose: Postprandial heartburn in GERD results from esophageal acid exposure; however, it is not known whether esophageal acidic reflux in GERD differs from that in normal subjects in only a quantitative manner or whether other unique properties define this disorder. This lack of information has resulted largely from the lack of suitable methods to analyze pH recordings. The aim of this study is to use novel analytic approaches to assess the pattern and extent of esophageal acid exposure in GERD and to determine the extent to which they differ from normal. Methods: Subjects were 57 patients with heartburn at least 4 times per week for more than 6 months and 26 healthy subjects. Esophageal pH and gastric pH were recorded continuously for 24 hours and analyzed for every 4 –second interval using custom software. Esophageal reflux was defined as esophageal pH⬍4 for at least 4 seconds. Integrated acidity was calculated as the time–weighted average of the acid concentration every second of the recording period. Results: In both GERD and normal subjects, at least 80% experienced esophageal reflux between 10:00 –22:00. At least 40% of GERD patients and 20% of normal subjects had nocturnal esophageal reflux between 22:00 – 8:00. In GERD, the number of reflux episodes during each hour or during the entire 24 – hour recording period did not differ from those in normals. In GERD, median integrated esophageal acidity (16.02 mmol.hr/L) and time esophageal pH⬍4 (9.6%) were much higher than corresponding values from normals (2.37 mmol.hr/L and 3.0%; P⬍0.0001). The median esophageal acid concentration during reflux episodes in GERD (6.6mM) was higher than that in normals (3.9mM; P⫽0.0049). Furthermore, in GERD but not in normals, there was a direct correlation between esophageal acid concentration during reflux episodes and postprandial gastric acidity (r⫽0.36; P⫽0.0067). Conclusions: The present results indicate that GERD is characterized by a normal pattern of esophageal reflux but with increased esophageal acid concentration during reflux episodes. This abnormality, in turn, is consistent with increased postprandial gastric acidity being a primary pathophysiologic abnormality in GERD. 2 INCREASED POSTPRANDIAL GASTRIC ACIDITY IS A MAJOR PATHOPHYSIOLOGIC ABNORMALITY IN GASTROESOPHAGEAL REFLUX DISEASE Jerry D. Gardner*, Sheila Rodriguez–Stanley, Malcolm Robinson, Sheldon Sloan and Philip B. Miner, Jr. Science for Organizations, Inc, Chatham, NJ; The Oklahoma Foundation for Digestive Research, Oklahoma City, OK and Janssen Pharmaceutica, Titusville, NJ. Purpose: Postprandial heartburn in GERD results from reflux of gastric acid into the esophagus. Even though GERD has long been considered to

be a motility disorder, no consistent, etiologic motility disturbance has been identified. We considered the possibility that increased postprandial esophageal acid exposure in GERD might be caused by increased postprandial gastric acidity. Previously, we found that after a meal, postprandial integrated gastric acidity correlates closely with meal–stimulated gastric acid secretion. In the present study, we measured esophageal acid exposure and integrated gastric acidity in healthy subjects and patients with GERD to determine whether postprandial integrated gastric acidity after multiple meals can also be used as a surrogate for meal–stimulated gastric acid secretion. Methods: Subjects were 26 healthy subjects and 57 patients with GERD who experienced heartburn at least 4 times per week for more than 6 months. Gastric and esophageal pH were measured continuously for 24 hours during which time subjects ingested 3 standard meals. Meal–stimulated gastric acid secretion in healthy subjects was measured by in vivo gastric autotitration – a recently developed technique that measures gastric secretion under physiological conditions. Results: In healthy subjects, meal–stimulated gastric acid secretion correlated directly with postprandial integrated gastric acidity from 8:00 –22:00 (r⫽0.56; P⫽0.0031), but not with basal integrated gastric acidity from 0:00 – 8:00 (r⫽0.09; P⫽0.6301). In GERD patients, integrated esophageal acidity (16.02 mmol.hr/L) and time esophageal pH⬍4 (9.6%) were higher than corresponding control values (2.37 mmol.hr/L and 3.0%; P⬍0.0001). Postprandial integrated gastric acidity in GERD patients (575 mmol.hr/L) was higher control (367 mmol.hr/L; P⫽0.0109); whereas basal integrated acidity in GERD patients (1793 mmol.hr/L) was not different from control (1848 mmol.hr/L; P⫽0.3190). Conclusions: The present results indicate that increased postprandial gastric acidity, which reflects increased meal–stimulated gastric acid secretion, can account for the increased esophageal acid exposure in GERD and may be the primary etiologic event in individuals who experience recurrent meal–induced heartburn. 3 ESOPHAGITIS IN CHILDREN AND ADULTS WITH CYSTIC FIBROSIS Khalid Khan, M.B.Ch.B., Sara Jane Schwarzenberg, M.D., Lance Ferrrin, M.D. and Jordan Dunnitz, M.D.*. Pediatrics, University of Minnesota, Minneapolis, MN and Internal Medicine, University of Minnesota, Minneapolis, MN. Purpose: The prevalence of gastroesophageal reflux disease (GERD) is reported to be up to 80% in adults with Cystic Fibrosis (CF). An increased risk of Barrett’s metaplasia has also been proposed in the pediatric population with CF. However there is very little supportive evidence that severe esophagitis is a significant problem in this population. Methods: We examined upper intestinal autopsy data from 126 individuals with CF performed at the University of Minnesota between 1956 and 2002. Eighty–two were adults, age range 18 –50 (mean 24.9 years). The 44 children were aged between 6 –18 (mean 8.5 years). The male to female ratio was 38:88. Data from infants was not included. Results: A complete autopsy evaluation was recorded in 116 cases (75 adults). Superficial erosions, erythema, congestion, petechial or acute hemorrhage and cases where there was confusion with postmortem autolysis were excluded (hence esophagitis of grade 0 –1). Gastroduodenal inflam-

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mation was present only in adults: duodenal ulcer (n⫽2), gastric ulcer (n⫽2), chronic gastritis (n⫽3). Esophageal inflammation was present in 1 child: an 8 year– old with infective esophagitis. Grade 2– 4 esophagitis was present in 7 adults, the mean age of the adults was (26.1 years). Overall upper intestinal abnormalities were found in 18.7% of adults, moderately severe esophagitis was present in 9.3% of autopsied cases. There were no cases of Barretts. Conclusions: Our data shows that upper gastrointestinal inflammation is not an issue in childhood but prevalent in the adult CF population. Moderate to severe esophagitis is the most common finding but is much less common than proportion of individuals symptomatic of GERD. Prospective studies are required in the growing adult CF population to examine these findings. 4 INCIDENCE OF GERD: POST H.PYLORI ERADICATION Vijaypal Arya, M.D.*, Vipin Gupta, M.D., Parisga Ghovanlou, Diane Alaimo and Marina Krasnapolsky. Division of Gastroenterology, Wyckoff Heights Medical Center, Brooklyn, NY. Purpose: It has been proposed that H. Pylori is a biological H2 blocker hence eradication of H. pylori has been associated with worsening of reflux symptoms. To find out the effect of H. Pylori eradication, we did this retrospective study. Methods: We reviewed all the H pylori positive patients’ charts seen from January 2001 to December 2001.H. Pylori infection was diagnosed by pan– endoscopy /biopsy and/or Urea Breath test. The indications for H pylori eradication were gastric ulcer, duodenal ulcer and non ulcer dyspepsia. Results: Of total 100 H. Pylori positive patients, 30 had gastric ulcer, 40 had duodenal ulcer and 30 were non ulcer dyspepsia. 35 patient had associated heart burn (5/30 GU, 10/40 DU and 20/30 NUD).All patients were treated with prevpac. H Pylori eradication was documented by breath test. Only 10% patient needed second course of antibiotics. At 3 and 6 months follow– up only 4 patients (1 of GU group, 1of DU and 2 of NUD group) continued to complain of heart burn. All 4 patients had history of heart burn before H. Pylori eradication. Post H Pylori eradication none of the patient developed heart burn as a new symptom. Conclusions: This retrospective review does not favor the notion that H pylori eradication increases the incidence of GERD or exacerbate the symptoms of GERD. TO confirm this large prospective study is needed. 5 ARE TEN WET SWALLOWS AN APPROPRIATE SAMPLE OF ESOPHAGEAL MOTILITY? YES AND NO Sajid Jalil, M.D., Monicca Sperandio, M.D., Shirley Jamieson, Lileeth Kong, R.N., June Castell, M.S., FACG and Donald O. Castell, M.D., M.A.C.G.*. Gastroenterology & Hepatology, Medical University of South Carolina, Charleston, SC. Purpose: To evaluate whether 10 wet swallows during esophageal manometry is an adequate sampling of esophageal motility. Methods: 100 consecutive patients from September 2001 to January 2002, who underwent routinely scheduled esophageal manometry were studied. This included 36 males and 64 females with mean age of 51 (range 21– 85). The standard manometry technique in our laboratory was performed using 10 wet swallows (5 ml water) with the pressure transducers placed 4cm and 9 cm above the lower esophageal sphincter (LES). This was followed by an additional 10 wet swallows. The initial 10 swallows were interpreted by the usual routine during a regular analysis session. The additional 10 swallows were blinded and separately analyzed, then compared to the initial swallows for each patient. Patients with aperistalsis were excluded from the study. Results: Of the 100 studies, 91 had a consistent diagnosis for both pairs of 10 swallows; 56 normal, 19 ineffective esophageal motility (IEM), 10 nutcracker esophagus, and 5 diffuse esophageal spasm (DES). 1 patient was diagnosed to have a major motility disorder due to diabetes.The number of

AJG – Vol. 97, No. 9, Suppl., 2002

abnormal swallows (ineffective or simultaneous) differed between the two sets of 10 swallows in the remaining 9 patients, but the final diagnosis remained the same when comparing number of abnormal swallows in first ten versus the entire 20 swallows. In only one patient the diagnosis changed from normal to IEM and in one from DES to normal. Correlation between different variables is shown below: Correlation of swallow parameters between 1st and 2nd set of wet swallows Swallow parameters Number of effective peristalsis Number of ineffective contractions Number of simultaneous contractions Average amplitude (mm Hg) Average duration (sec)

r value

p value

0.81 0.84 0.85 0.96 0.88

⬍0.05 ⬍0.05 ⬍0.05 ⬍0.05 ⬍0.05

Conclusions: Standard esophageal manometry performed with a set of 10 wet swallows is adequate for making a manometric diagnosis in the majority of patients. An extra 10 wet swallows may help clarify the diagnosis of IEM or DES in about 2% of patients. 6 IS PPI MAINTENANCE THERAPY INDICATED IN BARRET’S METAPLASIA TO DECREASE THE INCIDENCE OF CARCINOMA OR DYSPLASIA–A SINGLE AND MULTICENTER STUDY Simmy Bank, M.D.*, Pankaj Singh, M.D., Nakechand Pooran, M.D. and Anant V. Indaram, M.D. Long Island Acid Related Study, Long Island Jewish Medical Center, Albert Einstein College of Medicine, New Hyde Park, NY. Purpose: To investigate the prevalence and incidence of of carcinoma/ dysplasia in patients with Barrets metaplasia with and without maintenance PPI therapy over a 6 –12 year period. Methods: This study comprised two groups.Group I consisted of prospective study of 140 patients followed for 6 –12 years on maintenance omeprazole either 20 mg alternate days or 20 – 60 mg daily for protracted heartburn. Sixty five had Barret’s esophagus. None of the remaining 75 developed Barret’s metaplasia, dysplasia or carcinoma over this period.All were endoscoped every 1–2 years during the study period. Group II , a questionaire returned from 25 GI group(60 individual gastroenterologists) on Long island comprised 1461 patients with Barrets esophagus reviewed retrospectively. Sixteen groups maintained patients on omeprazole and 9 treated for symptoms only. Results: The table shows the prevalence and incidence off and on maintenance PPI therapy.Prevalence is defined as as the finding of Carcinoma, High grade Dysplasia or Low grade Dysplasia at or within one year of the initial endoscopy and incidence was defined as finding of CA,HGD or LGD on 6 –12 years of follow up in group I and 5 years or more of surveillance in group II.Both groups showed a fairly high prevalence rate of 4% for CA,HGD and LGD.On the other hand the incidence was low,only one patient developing LGD in group I over 6 –12 yrs.The arithmetic incidence of CA and LGD in group II showed a reduction in CA in those patients on PPIs (0.1%) vs (0.3%) over 5 year period.Although in both the treated and untreated groups incidence was low study tended to show that continued PPI use reduced the incidence of dysplasia and carcinoma in Patients with Barrets esophagus. (table I) Prevalence and incidence of CA.HGD and LGD on followup

Prevalence Incidence Incidence on PPIs

CA

HGD

LGD

CA

HGD

LGD

3.8%

5.8%

5.7%

0%

0%

1.8%

4.6% 0.3% 0.1%

3.3% 0.6% 0.6%

2.4% 1.8% 1.2%

Conclusions: This study showed a trend towards decreased dysplasia and carcinoma in patients maintained on PPI therapy for Barrett’s metaplasia with an incidence of carcinoma 0.1% over 5 years in 1461 patients studied