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The diagnostic value of endoscopic biopsy in patients with nonerosive gastroesophageal reflux disease
AGAA1 237
April 2000
5664
5666
MAXIMAL OR NEAR-MAXIMAL INHIBITION OF ESOPHAGEAL ACIDITY BY THE 1ST DOSE OF RABEPRAZOLE IN GE RD.
IS THERE ANY SIGNIF ANCE IN THE DIFFERENT TYPES OF COLUMNAR MUCOSA IN BARRETT 'S ESOPHAGUS?
Jerry D. Gardner, Sheldon Sloan, Jay A. Barth, Sheila Rodriguez-Stanley, Malcolm G. Robinson, Sci for Organizations. Chatham, NJ; Janssen Pharmaceutica Products, L P, Titusville, NJ; Eisai Inc, Teaneck. NJ; Oklahoma Fdn for Digest Research. Oklahoma City, OK. Introduction. In many investigations of gastric antisecretory agents, only gastric acidity has been assessed. Other studies have focused only on esophageal pH. Despite the fact that gastric acidity is directly involved in the pathogenesis of acidic gastroesophagea l reflux, there has been little effort to examine possible relationships between gastric and esophageal acidity, particularly the extent to which gastric acidity must be reduced by an antisecretory agent in order to normalize esophageal acid exposure. Methods. Intragastric and intraesophageal pH profiles were measured in 19 patients with GERD documented by history and esophageal pHoS4 for at least 10% of a 24-hour recording period. Gastric and esophageal pH were measured at baseline and after I and 7 days of dosing with 20mg rabeprazole. Effects of rabeprazole after 7 days of dosing were assumed to represent maximal, steady-state inhibition. Values for pH were converted to acid concentration (mM) and integrated acidity was calculated from the cumulative, time-weighted means of the acid concentrations for every second of the 24-hour recording period. Integrated acidity (mmol.hr/L) was assessed over I-hour intervals. Patients were stratified based on 24-hour integrated esophageal acidity as monophasic (50% of total acidity occurring by hours 8-9; n= II) or bipha sic (50% of total acidity occurring by hours 17-18; n= 8). Results. Maximal rabeprazole inhibition of integrated gastric acidity was 88::'::5 % (mean::'::SEM) in monophasic patients and 85::'::5 % in biphasic patients. Maximal inhibition of integrated esophageal acidity was 95::'::3% in monophasic patients and 96::'::1 % in biphasic patients. Inhibition of integrated gastric acidity with the Ist dose of rabeprazole was 77::'::5% of maximal in monophasic patients and 70 ::':: 13% of maximal in biphasic patients. Inhibition of integrated esophageal acidity with the 1st dose of rabeprazole was 81::'::7% of maximal in monophasic patients and 94::'::4% in biphasic patients. Conclusion. The present results demonstrate that the Ist dose of rabeprazole produces maximal or near maximal inhibition of esophageal acidity and this inhibition is more pronounced than the concurrent reduction in gastric acidity. particularly in biphasic patients who have substantial esophageal reflux.
5665 APPROPRIATENESS OF LONG-TERM PROTON PUMP INHIBITOR PRESCRIBING PRACTICE S IN A TERTIARY CARE TEACHING HOSPITAL. Roger L. Gebhard, Samuel B. Ho, John P. Toscano, Kathleen J. Ellingson, Cheryl Schultz, Robert Hoolihan, Regions Hosp, St. Paul, MN; Veterans Affairs Med Ctr, Minneapolis, MN. Proton pump inhibitors are potent and effective agents for gastric acid suppressio n. Because they are expensive drugs whose use has increased markedly, appropriate use is important. We reviewed medical records to determine appropriateness of long-term proton pump inhibitor prescriptions in a large academic medical center. Medical records of patients having proton pump inhibitor therapy initiated between September, 1990 and May. 1996 and continued > 120 consecut ive days were identified from Pharmacy Service computer records. One hundred charts (30% of 329 eligible) were randomly selected and reviewed for treatment indication. Predetermined indication s criteria for appropriate long-term use were based upon peptic ulcer and gastroeso phageal reflux treatment guidelines from the American College of Gastroenterology, indications then-current Physicians' Desk Reference. and other sources. Long-term prescriptions were considered appropriate in 52 of 100 instances and inappropriate in 26 of 100. Indications for 22 were considered marginal. Complicated gastroesophageal reflux was the most common ly stated indication (40 of 100), and review showed no inappropriate use. Inappropriate use occurred when the initial indication was therapeutic trial for uncomplicated reflux symptoms (I I of 32), peptic ulcer history (6 of 10), chest pain (2 of 2), or dyspepsia (5 of 5). Treatment initiated by gastroentero logists were considered appropriate 72.5% of the time. but initiation by non-specialists was appropriate in only 30%. One-quarter of long-term proton pump inhibitor therapy may be inappropriate. Poor initial treatment plan, inadequate follow-up, and lack of reevaluation contributed to inappropriate use.
Fadi Gebrail, John M. Wo, Stephanie Mayfield-Stokes, Mukunda B. Ray, Univ of Louisville, Louisville, KY. Specialized intestinal metaplasia (SIM) is required for the diagnosis of clincally important Barrett' s esophagus. The significance of the underlying non-intestinal columnar mucosa is believed not to be clinically relevant. Aim: I) To determine the prevalance of different types of colu mnar mucosa in a large prospective database of Barrett ' s esophagus. 2) To determine the significance of underlying columnar mucosa with respect to SIM and dysplasia (Dys). Methods: 55 pts with endoscopic evidence of columnar-lined mucosa (CLE) underwent 88 upper endoscopies. 32 pts had short CLE (oS2cm) & 23 pts had long CLE (>2cm). A total of 651 biopsies (bx's) were obtained. The pathologist was blinded to pt' s clinical history, length of CLE and level of bx. The mucosa of each bx was categorized into one of the following: I)squamous, 2)junctional (both squmaous & columnar mucosa). 3)cardiac/pyloric (mucosa similar to that in cardiac and pyloric areas), or 4)fundic (presence of parietal or chief cells). The presence of SIM and Dys were determined for each bx. Results: The yield of SIM and Dys for each type of mucosa is presented in the table below. The most common mucosa was cardiac/pyloric, 393/65 1 (60%), occurring mostly in pts with long CLE. The prevalence of SIM and Dys in cardiac/ pyloric and junctional mucosa were similar among pts with short CLE and among pts with long CLE. Fundic mucosa was found in only 46/651 (7%) with 1 bx showed SIM & none had Dys. The highest percentage of SIM was in biopsies with cardiac/pyloric mucosa (68%). Conclusion s: I)SIM and Dys are more likely to be associated with junctional and cardiac/ pyloric mucosa. 2)SIM and Dys are rare in fundic mucosa, which may have a low dysplastic potential. Yieldfor: Squamous (n=46) Junctional (n=162) Cardiac/pyloric (n=393) Fundic (0=46)
Intestinal metaplasia ShortClE long ClE 0/29 (0%) 23/85 (27%) 13/40 (33%) 0/21 (OOk)
0/17 (0%)
55177 (71%) 256/353 (73%) 1/25 (4%)
Dysplasia ShortClE long ClE 0/29 (0%) 7/85 (8%)
3140 (8%) 0121 (OOk)
0/17 (0%) 16177 (21%) 731353 (21%) 0125 (OOk)
5667 TilE DIAGNOSTIC VALUE OF ENDOSCOPIC BIOPSY IN PA· TlENTS WITH NONEROSIVE GASTROESOPHAGEAL REFLUX DISEASE. Lauren B. Gerson, Barbara Egbert, Roopali Bansal, George Triadafilopoulos. VA Palo Alto Health Care System, Palo Alto, CA. Background : The gold standard for the diagnosis of gastroesophageal reflux disease (GERD) in patients with Grade 0 (Savary Miller) disease remains 24-hour ambulatory esophageal pH monitoring. Aim: To determine whether endoscopic biopsy in patients with grade 0 GERD can be diagnostic of GERD compared to controls without GERD symptoms. Methods: We studied 27 adult male patients with GERD symptoms, abnormal DeMeester scores on 24-hour ambulatory esophageal pH testing. and grade 0 GERD. Control s were patients undergoing endoscopy for other reasons who had a normal endoscopic biopsy. All specimens were obtained within five centimeters of the gastroesophageal junction. Slides were reviewed by a pathologist who was unaware of the clinical diagnosis. A score (maximum 100) was calculated according to the presence of the following prognostic features: (I) epithelial changes (max 40 points): basal cell hyperplasia (20 points) and/or papillomatosis (20 points); (2) papillary height (max 30 points) classified as < 40% (10 points). 50% (20 points), or 2=75 % (30 points); (3) Epithelial thickness (max 30 points): 0.2-0.3 mm (30 points). 0.31-0.4 mm (20 points), 0.41 mm or higher (10 points). Cases were compared to controls using student' s t test. Results: The mean score in the 27 GERD cases (+ SEM) was 76 :': 3.8 compared to 44 ::':: 3.8 for the controls (p = 0.02). Compared to controls, patients with grade 0 GERD were more likely to have papillary height > 75%, epithelial thickness of 0.2-0.3 mm, and basal cell hyperplasia plus papillomatosis. Using a cutoff score of 50 points, the sensitivity for GERD was 85%, specificity 88%, and positive predictive value 96%. Conclusions: Grade 0 patients with a microscopic score over 50 have a 96% chance of having GERD. Further prospective testing of this scoring system compared to traditional 24-hour pH monitoring is warranted.
April 2000
5664
5666
MAXIMAL OR NEAR-MAXIMAL INHIBITION OF ESOPHAGEAL ACIDITY BY THE 1ST DOSE OF RABEPRAZOLE IN GE RD.
IS THERE ANY SIGNIF ANCE IN THE DIFFERENT TYPES OF COLUMNAR MUCOSA IN BARRETT 'S ESOPHAGUS?
Jerry D. Gardner, Sheldon Sloan, Jay A. Barth, Sheila Rodriguez-Stanley, Malcolm G. Robinson, Sci for Organizations. Chatham, NJ; Janssen Pharmaceutica Products, L P, Titusville, NJ; Eisai Inc, Teaneck. NJ; Oklahoma Fdn for Digest Research. Oklahoma City, OK. Introduction. In many investigations of gastric antisecretory agents, only gastric acidity has been assessed. Other studies have focused only on esophageal pH. Despite the fact that gastric acidity is directly involved in the pathogenesis of acidic gastroesophagea l reflux, there has been little effort to examine possible relationships between gastric and esophageal acidity, particularly the extent to which gastric acidity must be reduced by an antisecretory agent in order to normalize esophageal acid exposure. Methods. Intragastric and intraesophageal pH profiles were measured in 19 patients with GERD documented by history and esophageal pHoS4 for at least 10% of a 24-hour recording period. Gastric and esophageal pH were measured at baseline and after I and 7 days of dosing with 20mg rabeprazole. Effects of rabeprazole after 7 days of dosing were assumed to represent maximal, steady-state inhibition. Values for pH were converted to acid concentration (mM) and integrated acidity was calculated from the cumulative, time-weighted means of the acid concentrations for every second of the 24-hour recording period. Integrated acidity (mmol.hr/L) was assessed over I-hour intervals. Patients were stratified based on 24-hour integrated esophageal acidity as monophasic (50% of total acidity occurring by hours 8-9; n= II) or bipha sic (50% of total acidity occurring by hours 17-18; n= 8). Results. Maximal rabeprazole inhibition of integrated gastric acidity was 88::'::5 % (mean::'::SEM) in monophasic patients and 85::'::5 % in biphasic patients. Maximal inhibition of integrated esophageal acidity was 95::'::3% in monophasic patients and 96::'::1 % in biphasic patients. Inhibition of integrated gastric acidity with the Ist dose of rabeprazole was 77::'::5% of maximal in monophasic patients and 70 ::':: 13% of maximal in biphasic patients. Inhibition of integrated esophageal acidity with the 1st dose of rabeprazole was 81::'::7% of maximal in monophasic patients and 94::'::4% in biphasic patients. Conclusion. The present results demonstrate that the Ist dose of rabeprazole produces maximal or near maximal inhibition of esophageal acidity and this inhibition is more pronounced than the concurrent reduction in gastric acidity. particularly in biphasic patients who have substantial esophageal reflux.
5665 APPROPRIATENESS OF LONG-TERM PROTON PUMP INHIBITOR PRESCRIBING PRACTICE S IN A TERTIARY CARE TEACHING HOSPITAL. Roger L. Gebhard, Samuel B. Ho, John P. Toscano, Kathleen J. Ellingson, Cheryl Schultz, Robert Hoolihan, Regions Hosp, St. Paul, MN; Veterans Affairs Med Ctr, Minneapolis, MN. Proton pump inhibitors are potent and effective agents for gastric acid suppressio n. Because they are expensive drugs whose use has increased markedly, appropriate use is important. We reviewed medical records to determine appropriateness of long-term proton pump inhibitor prescriptions in a large academic medical center. Medical records of patients having proton pump inhibitor therapy initiated between September, 1990 and May. 1996 and continued > 120 consecut ive days were identified from Pharmacy Service computer records. One hundred charts (30% of 329 eligible) were randomly selected and reviewed for treatment indication. Predetermined indication s criteria for appropriate long-term use were based upon peptic ulcer and gastroeso phageal reflux treatment guidelines from the American College of Gastroenterology, indications then-current Physicians' Desk Reference. and other sources. Long-term prescriptions were considered appropriate in 52 of 100 instances and inappropriate in 26 of 100. Indications for 22 were considered marginal. Complicated gastroesophageal reflux was the most common ly stated indication (40 of 100), and review showed no inappropriate use. Inappropriate use occurred when the initial indication was therapeutic trial for uncomplicated reflux symptoms (I I of 32), peptic ulcer history (6 of 10), chest pain (2 of 2), or dyspepsia (5 of 5). Treatment initiated by gastroentero logists were considered appropriate 72.5% of the time. but initiation by non-specialists was appropriate in only 30%. One-quarter of long-term proton pump inhibitor therapy may be inappropriate. Poor initial treatment plan, inadequate follow-up, and lack of reevaluation contributed to inappropriate use.
Fadi Gebrail, John M. Wo, Stephanie Mayfield-Stokes, Mukunda B. Ray, Univ of Louisville, Louisville, KY. Specialized intestinal metaplasia (SIM) is required for the diagnosis of clincally important Barrett' s esophagus. The significance of the underlying non-intestinal columnar mucosa is believed not to be clinically relevant. Aim: I) To determine the prevalance of different types of colu mnar mucosa in a large prospective database of Barrett ' s esophagus. 2) To determine the significance of underlying columnar mucosa with respect to SIM and dysplasia (Dys). Methods: 55 pts with endoscopic evidence of columnar-lined mucosa (CLE) underwent 88 upper endoscopies. 32 pts had short CLE (oS2cm) & 23 pts had long CLE (>2cm). A total of 651 biopsies (bx's) were obtained. The pathologist was blinded to pt' s clinical history, length of CLE and level of bx. The mucosa of each bx was categorized into one of the following: I)squamous, 2)junctional (both squmaous & columnar mucosa). 3)cardiac/pyloric (mucosa similar to that in cardiac and pyloric areas), or 4)fundic (presence of parietal or chief cells). The presence of SIM and Dys were determined for each bx. Results: The yield of SIM and Dys for each type of mucosa is presented in the table below. The most common mucosa was cardiac/pyloric, 393/65 1 (60%), occurring mostly in pts with long CLE. The prevalence of SIM and Dys in cardiac/ pyloric and junctional mucosa were similar among pts with short CLE and among pts with long CLE. Fundic mucosa was found in only 46/651 (7%) with 1 bx showed SIM & none had Dys. The highest percentage of SIM was in biopsies with cardiac/pyloric mucosa (68%). Conclusion s: I)SIM and Dys are more likely to be associated with junctional and cardiac/ pyloric mucosa. 2)SIM and Dys are rare in fundic mucosa, which may have a low dysplastic potential. Yieldfor: Squamous (n=46) Junctional (n=162) Cardiac/pyloric (n=393) Fundic (0=46)
Intestinal metaplasia ShortClE long ClE 0/29 (0%) 23/85 (27%) 13/40 (33%) 0/21 (OOk)
0/17 (0%)
55177 (71%) 256/353 (73%) 1/25 (4%)
Dysplasia ShortClE long ClE 0/29 (0%) 7/85 (8%)
3140 (8%) 0121 (OOk)
0/17 (0%) 16177 (21%) 731353 (21%) 0125 (OOk)
5667 TilE DIAGNOSTIC VALUE OF ENDOSCOPIC BIOPSY IN PA· TlENTS WITH NONEROSIVE GASTROESOPHAGEAL REFLUX DISEASE. Lauren B. Gerson, Barbara Egbert, Roopali Bansal, George Triadafilopoulos. VA Palo Alto Health Care System, Palo Alto, CA. Background : The gold standard for the diagnosis of gastroesophageal reflux disease (GERD) in patients with Grade 0 (Savary Miller) disease remains 24-hour ambulatory esophageal pH monitoring. Aim: To determine whether endoscopic biopsy in patients with grade 0 GERD can be diagnostic of GERD compared to controls without GERD symptoms. Methods: We studied 27 adult male patients with GERD symptoms, abnormal DeMeester scores on 24-hour ambulatory esophageal pH testing. and grade 0 GERD. Control s were patients undergoing endoscopy for other reasons who had a normal endoscopic biopsy. All specimens were obtained within five centimeters of the gastroesophageal junction. Slides were reviewed by a pathologist who was unaware of the clinical diagnosis. A score (maximum 100) was calculated according to the presence of the following prognostic features: (I) epithelial changes (max 40 points): basal cell hyperplasia (20 points) and/or papillomatosis (20 points); (2) papillary height (max 30 points) classified as < 40% (10 points). 50% (20 points), or 2=75 % (30 points); (3) Epithelial thickness (max 30 points): 0.2-0.3 mm (30 points). 0.31-0.4 mm (20 points), 0.41 mm or higher (10 points). Cases were compared to controls using student' s t test. Results: The mean score in the 27 GERD cases (+ SEM) was 76 :': 3.8 compared to 44 ::':: 3.8 for the controls (p = 0.02). Compared to controls, patients with grade 0 GERD were more likely to have papillary height > 75%, epithelial thickness of 0.2-0.3 mm, and basal cell hyperplasia plus papillomatosis. Using a cutoff score of 50 points, the sensitivity for GERD was 85%, specificity 88%, and positive predictive value 96%. Conclusions: Grade 0 patients with a microscopic score over 50 have a 96% chance of having GERD. Further prospective testing of this scoring system compared to traditional 24-hour pH monitoring is warranted.