endoscopic impression of barrett esophagus: declining positive predictive value

1
W1292 Barretfs Esophagus in Unscreened, Older Patients Undergoing Screening or Follow-up Colonoscopy Eric M Ward, Kenneth R I)evault, Herbert C. Wolfsen David S. Loeb, Murli Krishna, Timothy A. Woodward, Lois L Hemminger, Frances K Cayer, Sami R. Achem Purpose: garrett's esophagus (BE) has been reported to be mme cmnmon in older patients. However, physiologic studies have demonstrated diminished esophageal sensation with aging Since current BE scmeinng recommendations focus on patients with symptmns of gastmesophageal retfux disease (GERD), (he patients at highest risk tor BE may not be screened This study seeks to determine the prevalence of BE in unscreened, older patients and the predmtabdity ot BE by GERD symptoms in this group. Methods: All patients older lban 65 years who were referred fbr outpatient colonoseopy and who had never previously undergone upper endoscopy were eligible for the study. Participants underwent upper endoscopy at the time of the scheduled colonoscopy During the procedure the presence of BE as well as other upper gastrointestinal (GI) pathology was identified. Biopsies were taken fi*om below the sqnarnocolnmnar junction (S(J) in all patients and reviewed by a single, dedicated pathologist The patients also completed a questionnaire pertaining to GERD symptoms This report describes the first 61 patients of this study. Results: The average age of the participants was 729 years with a male:female ratio of 32:29. BE was present in 5 patients (8,2%) 4 of 5 BE patients were male (BE prevalance 12.5% in males, 3 4% in kmales) The mean age of patients with BE was 70.4 years 1"he length of the metaplasia was <2 cm in 4/5. Dysplasia was not present m arty patient. Intestinal metaplasia of the gastric cardia (1MGC) was present in I0 (16%) Of the patients with BE, heartburn or regurgitation occmTed once a week or less in 4/5 and not at all in the fifth. The patient with long segment BE (8cm) was asymptomatic with the exception of rare "belching" GERD symptoms were present in half of the patients with IMGC. Other endoscopic findings included erosive esophagitis (4), para<sophageal hernia (1), esophageal ring (1), gastritis/ gastric erosions (7) gastric polyps (2) gastric ulcers (2), gastric nodules (1), and inlet patch (]) H pyiori was present m 7 of the patients with gastritis or ulcers (biopsy taken at discretion of endoscopist). Conclusions: BE may occur in older patients (particularly men) with mild or intrequent GERD symptoms. IMGC is twk'e as common as BE in this age group, but the significance of this finding is unclear This study continues to enroll patients to help to determine if the current BE screening recommendations are adequate for the detection of BE in an older population W1293 Endoscopic Impression of Barrett Esophagus: Declining Positive Predictive Value Kuldip S Banwait Parveen S Bamvait, Anthony Dimarmo, Thomas Kowalski Introduction:The association of Barrett's esophagus (BE) with adenocaminoma has increased physician's dforts towards establishing its diagnosis, Such efforts include greater diligence in ~nding patien s with gastroesophagea/reflux disease for EGD and upon EGD, closer inspectinn of he squamocolumnar junction wish biopsy of endoscopic abnormalities, Ahbough the dmgnosis is estabIished by histology, an endoscopic suspicion of BE is ofien p*erequisite for a biopsy to be obtained A decreased threshold for obtaining biopsies hovr wdl tesult in a lower positive predictive value of the endoscopic impression of BE as compared to the specificity of this endoscopic finding previnudy reported as 81%. Methods:S600 corrsecntlve patients reterred tbr endoscopy in our tertiary care center were included m this retrospective study Results:Ot 5600 EGD examinations, art endoscopic inrpmssiou of BE was noted m 436 patients (7,8%). This group had a mean age of 58.6 years and consisted of 58.7% male 41.3% temale, 67.8% Caucasian, 9.9% black, and 22.3% other race patients Of these patients, gastroesophageaI junction histology was available in 385 patients and 157 patients were confirmed to have BE by histopathology (2.8%). When patients with a par-procedure diagnosis of BE were excluded, 272 patients with a naive endoscopic impression of BE remained. 88 ot the 272 patients with a nave endoscopic impression of BE were"confirmed to have BE by histopatholoD", yielding a positive predictive value of 323% The age, sex, and race characteristics of these 88 patients did not significantly differ fi'om the above group of pat*ents with an endoscopic impression of BE, Conclusions: 1. Of 5600 consecutive EGD procedures, the petvent of newly diagnosed BE patients (1.6%) was similar to the 1 4% reported in the literature, 2, The positive predictive value of an endoscopic impression oI BE was 323% 3 While a decreased threshold for obtaining biopsies has lowered the positive predictive value of an endoscopic impression of BE, it has not irrcreased the pememage of patients that are newb/diagnosed with BE. 4, More specific methods to direct endoscopic biopsies tor BE are necessary. W1294 Clinical Predictive Factors for Long-Segment Barretfs Esophagus Colleen Green, William D Chey, Michael P Jones, Glenn M Eisen, Michael Briseno Harinder S Garewal, Ronnie Fass Background: Several clinical tactors have been s:nown to be associated with Barrett's length (acid exposm'e, LES pressure, hiatal hernia length, etc.), However, systematic assessment of vanous clinical factors as predictors of long-segment Barrett's esophagus (BE) has yet to be carried out Aim: To determine which clinical factors are highly predictive of long-segment Barrett's esophagus Methods: Patients ruth diagnosed Barmtt's esophagus were recruited into the study honl 4 academic centers in the US AI/patients had an upper endoscopy revealing a salmon<olored tongue extending into the esophagns (any length) that was positive for inmstinal metaplasla Presence of dysplasia or adenocarcinoma was documented as weft Patients were evaluated by a validated demographic questionnait~ and the GERD Symptom Checklist, Short-segment BE was defined as length <3cm and long-segrnent BE as length >3cm Results: Oue-hnndred sixty-two BE patients were recruited into the study" (130M, mean age 637_+ 10, range ]9-85 years) Ot those, 80 (49%) had short-segment and 82 (51%) long-segment BE. Mean Barrett's length for the entire sample was 3,67 -+ 0.24cm (range 0 5-18cm) Older patients (~6fJ ,rears, OR= 1.52), Caucasians (OR=2.64) and overweight patien s (BMI>25, OR= 13) were more likely to harbor long-segment BE as compared to younger patients (<60 years), non-Caucasians and lean subjects (BMl<25), Patients with dysplasia (indefinite, low grade or high grade) or cancer were also more likely to have long-segment BE (OR = 3,07), When these histopathological findings were separated further, those who had high-grade dysplasia or cancer were 4,5 times more likely to have long-segnlent BE than patients without high-grade dysplasia or cancer. Patients withindefinite or low-grade dysplasia were 2.6 times more fikdy to have long-segment BE than patients without dysplas/a. Patients with a prior history of upper GI surgery were more likely to have long-segment BE than those without history of upper GI surgery (OR= 2.68). Conclu- sions: Patients who are older, Caucasian, overweight, with a history of upper GI surgeD', dysplasia or esophageal cancer are more likely to have long-segment Barrett's esophagus. W1295 Not Only Reflux Esophagitis But H.Pylori Infection May Be a Causal Factor for The Inflammation of Columnar-Lined Esophagus Yoshifumi Inomata, Shuichi Ohara, Yasuhiko Abe, Tomoyuki Koike, Hitoshi Sekine, Katsunori liiima, Masashi Kawamnra, Naohiro Dairaku, Akira Imatani, Katsuaki Kato, Toora Shimosegawa Background and Aims: The inflammation and intestinal metaplasia (1M) of the gastric cardia is closely associated with H.pylori (HP) intection, whereas the inflammatory level and pattern of metaplastic columnar epithelium of the esophagus is not well investigated. The aim of this study was to perform a histological assessment of the inflammation and IM in the cardia and columnatqined esophagus (CLE) and to evaluate the effect of HP infection and reflux esophagitis (RE) on it. Materials and Methods: A total of 43 patients with CLE were enrolled in this study. CLE was endoscopicafiy diagnosed by the presence of a red and tongue-like columnar epithelium in the distal esophagus. Of 43 patients with CLE, the length of columnar epithelium was 3cm or more in 11 patients and less than 3cm in 32 patients. Biopsies were taken from the proximal margin of the gastric folds (card/a), esophageal columnar epithelium, and from the gastric body and the antrum. Updated Sydney system was applied to the histological assessment for the inflammation and IM. The inflammation, activity and IM were scored from 0 to 3, and the sum of the former two scores was defined as INF score. The stares of gastric HP infection was detemlined by histology, rapid urease test, and detection of serum IgG antibodies RE was diagnosed according to the Los Angeles classifica- tion. Patients who were taking PPI were excluded. Results: Of 43 patients, RE was found in 27 and HP infection was present in 15. The INF score of the cardia was significantly higher in the patients with HP than in those without HP regardless of the presence or absence of RE. IM of the cardia is present only in the HP-positive patients without RE. The INF score of CLE was significantly higher in the patients with HP than in those without HP when examined in the patients without RE, whereas it was not difierent between the patients with and without tiP infection when examined in the patients with RE. The IM score of the CLE tended to be high in the HP-positive patients without RE, ahhough it was not significantly difterent according to the presence or absence of HP infection and RE. The IM score of CLE was significantly higher in the patients with its length of 3cm or more than in those with less than 3cm, but the 1NF score of CLE was not different between these two groups. Conclusion: Not only RE but H.pylori infection may" be a causal factor for the inflammation of CLE W1296 Expression of the CDX2 homeobox protein in Barrett's Metaplasia (BM) Nell Kapoor, Mel Hulbert, M Haqquani, Lugang Yn, Keith Bodger BACKGROUND Cdx2 is an intestinal transcription factor that is a key regulator of develop- ment and homeostasis of intestinal epithelium. In the adult, Cdx2 expression is confined to the small and large intestine. Neo-expression occurs in gastric intestinal metaplas/a and ectopic gastric expression of Cdx2 leads to an intestinalized mucosa in tmnsgenic mice. Preliminary reports suggest that Cdx2 is expressed in BM We aimed to examine Cdx2 expression within various histological sub-types of BM and during malignant progression. METHODS With informed consent, 68 oesophageal surveillance biopsies from 52 patients with BM were studied. Formalin-fixed, paraffin-embedded sections were subject to immuno- histochemistry using an anti-Cdx2 mAb (BioGenex) and an automated avidin-biotin-based system. Control sections comprised normal colon and duodenum. Both H&E and mucin staining (Gomori's aldehyde fushcin) were employed in serial sections to identify and type loci of metaplastic epithehum. Nuclear immmmstaining was scored semi-qnantitatively (0- absent; 1-focally absent or weak; 2-strongly positive). We also screened confluent TE7 ceils (oesophageal adenocarcinoma) for Cdx2 expression by immunoblotting of cell lysates (CACO-2 cells were employed as positive control). RESULTS All examples of squamous macosa, cardiac/fundic-type glands and deep oesophageal glands were negative for Cdx2 expression. Staining intensity within intestinal-type mucosa and dysplasia is shown in the Table. No Cdx2 expression was identified in immunoblots of TE7 adenocarcinoma cells. CONCLUSIONS Neo-expression of Cdx2 is almost invariable in SIM but does not occur in gastric-type variants of Barrett*s oesophagus. Down-regulation of Cdx2 may occur during oesophageal malignant progression, consistent with a tumour suppressor function. The molecular mechanisms regulating Cdx2 expression during oesophageal carcinogenesis require further study. Oesophagealtissue type Score 0 Score I Score 2 Spedalized intestinal m~aplas|a (SIM) 0 5 40 Indefinitefor dysplula (IFD) 0 2 2 Low grade dy,~sl= (LGD) 0 7 0 High grade ~ a ~ z (HGD) 2 0 1 , SIM v IFD/LGD/HGD (pooled scores: 0-1 v 2), p<0.01, AGA Abstracts A-642

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Page 1: Endoscopic impression of Barrett esophagus: Declining positive predictive value

W1292

Barretfs Esophagus in Unscreened, Older Patients Undergoing Screening or Follow-up Colonoscopy Eric M Ward, Kenneth R I)evault, Herbert C. Wolfsen David S. Loeb, Murli Krishna, Timothy A. Woodward, Lois L Hemminger, Frances K Cayer, Sami R. Achem

Purpose: garrett's esophagus (BE) has been reported to be mme cmnmon in older patients. However, physiologic studies have demonstrated diminished esophageal sensation with aging Since current BE scmeinng recommendations focus on patients with symptmns of gastmesophageal retfux disease (GERD), (he patients at highest risk tor BE may not be screened This study seeks to determine the prevalence of BE in unscreened, older patients and the predmtabdity ot BE by GERD symptoms in this group. Methods: All patients older lban 65 years who were referred fbr outpatient colonoseopy and who had never previously undergone upper endoscopy were eligible for the study. Participants underwent upper endoscopy at the time of the scheduled colonoscopy During the procedure the presence of BE as well as other upper gastrointestinal (GI) pathology was identified. Biopsies were taken fi*om below the sqnarnocolnmnar junction (S(J) in all patients and reviewed by a single, dedicated pathologist The patients also completed a questionnaire pertaining to GERD symptoms This report describes the first 61 patients of this study. Results: The average age of the participants was 729 years with a male:female ratio of 32:29. BE was present in 5 patients (8,2%) 4 of 5 BE patients were male (BE prevalance 12.5% in males, 3 4% in kmales) The mean age of patients with BE was 70.4 years 1"he length of the metaplasia was < 2 cm in 4/5. Dysplasia was not present m arty patient. Intestinal metaplasia of the gastric cardia (1MGC) was present in I0 (16%) Of the patients with BE, heartburn or regurgitation occmTed once a week or less in 4/5 and not at all in the fifth. The patient with long segment BE (8cm) was asymptomatic with the exception of rare "belching" GERD symptoms were present in half of the patients with IMGC. Other endoscopic findings included erosive esophagitis (4), para<sophageal hernia (1), esophageal ring (1), gastritis/ gastric erosions (7) gastric polyps (2) gastric ulcers (2), gastric nodules (1), and inlet patch ( ] ) H pyiori was present m 7 of the patients with gastritis or ulcers (biopsy taken at discretion of endoscopist). Conclusions: BE may occur in older patients (particularly men) with mild or intrequent GERD symptoms. IMGC is twk'e as common as BE in this age group, but the significance of this finding is unclear This study continues to enroll patients to help to determine if the current BE screening recommendations are adequate for the detection of BE in an older population

W1293

Endoscopic Impression of Barrett Esophagus: Declining Positive Predictive Value Kuldip S Banwait Parveen S Bamvait, Anthony Dimarmo, Thomas Kowalski

Introduction:The association of Barrett's esophagus (BE) with adenocaminoma has increased physician's dforts towards establishing its diagnosis, Such efforts include greater diligence in ~nding patien s with gastroesophagea/reflux disease for EGD and upon EGD, closer inspectinn of h e squamocolumnar junction wish biopsy of endoscopic abnormalities, Ahbough the dmgnosis is estabIished by histology, an endoscopic suspicion of BE is ofien p*erequisite for a biopsy to be obtained A decreased threshold for obtaining biopsies hovr wdl tesult in a lower positive predictive value of the endoscopic impression of BE as compared to the specificity of this endoscopic finding previnudy reported as 81%. Methods:S600 corrsecntlve patients reterred tbr endoscopy in our tertiary care center were included m this retrospective study Results:Ot 5600 EGD examinations, art endoscopic inrpmssiou of BE was noted m 436 patients (7,8%). This group had a mean age of 58.6 years and consisted of 58.7% male 41.3% temale, 67.8% Caucasian, 9.9% black, and 22.3% other race patients Of these patients, gastroesophageaI junction histology was available in 385 patients and 157 patients were confirmed to have BE by histopathology (2.8%). When patients with a par-procedure diagnosis of BE were excluded, 272 patients with a naive endoscopic impression of BE remained. 88 ot the 272 patients with a nave endoscopic impression of BE were" confirmed to have BE by histopatholoD ", yielding a positive predictive value of 3 2 3 % The age, sex, and race characteristics of these 88 patients did not significantly differ fi'om the above group of pat*ents with an endoscopic impression of BE, Conclusions: 1. Of 5600 consecutive EGD procedures, the petvent of newly diagnosed BE patients (1.6%) was similar to the 1 4% reported in the literature, 2, The positive predictive value of an endoscopic impression oI BE was 3 2 3 % 3 While a decreased threshold for obtaining biopsies has lowered the positive predictive value of an endoscopic impression of BE, it has not irrcreased the pememage of patients that are newb/diagnosed with BE. 4, More specific methods to direct endoscopic biopsies tor BE are necessary.

W1294

Clinical Predictive Factors for Long-Segment Barretfs Esophagus Colleen Green, William D Chey, Michael P Jones, Glenn M Eisen, Michael Briseno Harinder S Garewal, Ronnie Fass

Background: Several clinical tactors have been s:nown to be associated with Barrett's length (acid exposm'e, LES pressure, hiatal hernia length, etc.), However, systematic assessment of vanous clinical factors as predictors of long-segment Barrett's esophagus (BE) has yet to be carried out Aim: To determine which clinical factors are highly predictive of long-segment Barrett's esophagus Methods: Patients ruth diagnosed Barmtt's esophagus were recruited into the study honl 4 academic centers in the US AI/patients had an upper endoscopy revealing a salmon<olored tongue extending into the esophagns (any length) that was positive for inmstinal metaplasla Presence of dysplasia or adenocarcinoma was documented as weft Patients were evaluated by a validated demographic questionnait~ and the GERD Symptom Checklist, Short-segment BE was defined as length <3cm and long-segrnent BE as length > 3 c m Results: Oue-hnndred sixty-two BE patients were recruited into the study" (130M, mean age 637_+ 10, range ]9-85 years) Ot those, 80 (49%) had short-segment and 82 (51%) long-segment BE. Mean Barrett's length for the entire sample was 3,67 -+ 0.24cm (range 0 5-18cm) Older patients (~6fJ ,rears, OR= 1.52), Caucasians (OR=2.64) and overweight patien s (BMI>25, OR= 13) were more likely to harbor long-segment BE as

compared to younger patients (<60 years), non-Caucasians and lean subjects (BMl<25), Patients with dysplasia (indefinite, low grade or high grade) or cancer were also more likely to have long-segment BE (OR = 3,07), When these histopathological findings were separated further, those who had high-grade dysplasia or cancer were 4,5 times more likely to have long-segnlent BE than patients without high-grade dysplasia or cancer. Patients withindefinite or low-grade dysplasia were 2.6 times more fikdy to have long-segment BE than patients without dysplas/a. Patients with a prior history of upper GI surgery were more likely to have long-segment BE than those without history of upper GI surgery (OR= 2.68). Conclu- sions: Patients who are older, Caucasian, overweight, with a history of upper GI surgeD', dysplasia or esophageal cancer are more likely to have long-segment Barrett's esophagus.

W1295

Not Only Reflux Esophagitis But H.Pylori Infection May Be a Causal Factor for The Inflammation of Columnar-Lined Esophagus Yoshifumi Inomata, Shuichi Ohara, Yasuhiko Abe, Tomoyuki Koike, Hitoshi Sekine, Katsunori liiima, Masashi Kawamnra, Naohiro Dairaku, Akira Imatani, Katsuaki Kato, Toora Shimosegawa

Background and Aims: The inflammation and intestinal metaplasia (1M) of the gastric cardia is closely associated with H.pylori (HP) intection, whereas the inflammatory level and pattern of metaplastic columnar epithelium of the esophagus is not well investigated. The aim of this study was to perform a histological assessment of the inflammation and IM in the cardia and columnatqined esophagus (CLE) and to evaluate the effect of HP infection and reflux esophagitis (RE) on it. Materials and Methods: A total of 43 patients with CLE were enrolled in this study. CLE was endoscopicafiy diagnosed by the presence of a red and tongue-like columnar epithelium in the distal esophagus. Of 43 patients with CLE, the length of columnar epithelium was 3cm or more in 11 patients and less than 3cm in 32 patients. Biopsies were taken from the proximal margin of the gastric folds (card/a), esophageal columnar epithelium, and from the gastric body and the antrum. Updated Sydney system was applied to the histological assessment for the inflammation and IM. The inflammation, activity and IM were scored from 0 to 3, and the sum of the former two scores was defined as INF score. The stares of gastric HP infection was detemlined by histology, rapid urease test, and detection of serum IgG antibodies RE was diagnosed according to the Los Angeles classifica- tion. Patients who were taking PPI were excluded. Results: Of 43 patients, RE was found in 27 and HP infection was present in 15. The INF score of the cardia was significantly higher in the patients with HP than in those without HP regardless of the presence or absence of RE. IM of the cardia is present only in the HP-positive patients without RE. The INF score of CLE was significantly higher in the patients with HP than in those without HP when examined in the patients without RE, whereas it was not difierent between the patients with and without tiP infection when examined in the patients with RE. The IM score of the CLE tended to be high in the HP-positive patients without RE, ahhough it was not significantly difterent according to the presence or absence of HP infection and RE. The IM score of CLE was significantly higher in the patients with its length of 3cm or more than in those with less than 3cm, but the 1NF score of CLE was not different between these two groups. Conclusion: Not only RE but H.pylori infection may" be a causal factor for the inflammation of CLE

W1296

Expression of the CDX2 homeobox protein in Barrett's Metaplasia (BM) Nell Kapoor, Mel Hulbert, M Haqquani, Lugang Yn, Keith Bodger

BACKGROUND Cdx2 is an intestinal transcription factor that is a key regulator of develop- ment and homeostasis of intestinal epithelium. In the adult, Cdx2 expression is confined to the small and large intestine. Neo-expression occurs in gastric intestinal metaplas/a and ectopic gastric expression of Cdx2 leads to an intestinalized mucosa in tmnsgenic mice. Preliminary reports suggest that Cdx2 is expressed in BM We aimed to examine Cdx2 expression within various histological sub-types of BM and during malignant progression. METHODS With informed consent, 68 oesophageal surveillance biopsies from 52 patients with BM were studied. Formalin-fixed, paraffin-embedded sections were subject to immuno- histochemistry using an anti-Cdx2 mAb (BioGenex) and an automated avidin-biotin-based system. Control sections comprised normal colon and duodenum. Both H&E and mucin staining (Gomori's aldehyde fushcin) were employed in serial sections to identify and type loci of metaplastic epithehum. Nuclear immmmstaining was scored semi-qnantitatively (0- absent; 1-focally absent or weak; 2-strongly positive). We also screened confluent TE7 ceils (oesophageal adenocarcinoma) for Cdx2 expression by immunoblotting of cell lysates (CACO-2 cells were employed as positive control). RESULTS All examples of squamous macosa, cardiac/fundic-type glands and deep oesophageal glands were negative for Cdx2 expression. Staining intensity within intestinal-type mucosa and dysplasia is shown in the Table. No Cdx2 expression was identified in immunoblots of TE7 adenocarcinoma cells. CONCLUSIONS Neo-expression of Cdx2 is almost invariable in SIM but does not occur in gastric-type variants of Barrett*s oesophagus. Down-regulation of Cdx2 may occur during oesophageal malignant progression, consistent with a tumour suppressor function. The molecular mechanisms regulating Cdx2 expression during oesophageal carcinogenesis require further study.

Oesophageal tissue type Score 0 Score I Score 2 Spedalized intestinal m~aplas|a (SIM) 0 5 40 Indefinite for dysplula (IFD) 0 2 2 Low grade dy,~sl= (LGD) 0 7 0 High grade ~ a ~ z (HGD) 2 0 1 , SIM v IFD/LGD/HGD (pooled scores: 0-1 v 2), p<0.01,

A G A A b s t r a c t s A - 6 4 2