the relationship between gerd and osas and effects of anti-reflux therapy

1
A336 AGA ABSTRACTS • G1371 DOES HELICOBACTER PYLORI SEROLOGY PREDICT THE INTRAGASTRIC BACTERIAL DENSITY OF H. PYLORI AND THE HISTOLOGICAL SEVERITY OF GASTRITIS? HH-X Xia, J Kalantar, J Ma Wyatt, S Adams, K Cheung, H M Mitchell and NJ Talley. Departments of Medicine and Pathology, University of Sydney, Nepean Hospital, and School of Microbiology and Immunology, University of New South Wales, Australia BACKGROUND: Serology has been established as a sensitive and specific technique for detecting H. pylori infection. However, whether the level of the IgG response is predictive of the bacterial density of H. pylori and the severity of the associated gastritis is unknown. The aim of this study was to determine the association between anti-H, pylori IgG antibody levels and bacterial density and severity of inflammation in the stomach. METHODS: 208 patients with dyspepsia were enrolled. Eight biopsies, ie. antrum (A) x3, body (B) x2, fundus (F) x2 and incisura (I) xl were taken from each patient during gastroscopy. One antral biopsy was used for the CLO-test. Three (one each from A, B and F) were cultured. The remaining biopsies were examined histologically according to the updated Sydney System after staining with H&E and Giemsa. A validated ELISA test was used to detect specific anti-H, pylori IgG antibodies and the absorbance index (AI) was applied to estimate the IgG titers. RESULTS: Overall, 84 patients (40%) were diagnosed as positive for H. pylori by CLO-test, histology and/or culture. The AI was significantly lower in the H. pylori negative patients than in positive patients (0.10 _+ 0.20 (mean _+ SD) vs 0.88 _+ 0.36, p < 0.001, t-tests). The associations of the AI with bacterial density and severity of gastritis at different gastric sites are shown in the table. Absorbance index (mean) Gastric sites Bacterial Densitv a Severity of Gastritis b Active Gastritis + ++ +++ - + ++ +++ Present Absent Antrum 0.82 0.86 0.98 0.08 0.44 0.83 1.07"* 0.87 0.14"* Incisura 0.06 0.49 0.87 1.05"* 0.82 0.18"* Body 0.75 0.96 1.03"0.10 0.63 0.97 1.06"* 0.84 0.19"* Fundus 0.10 0.70 0.92 0.84** 0.81 0.27** a, includes the gastric antral-type and body-type mucosa of positive patients. +, small number, ++, moderate number, +++, large number; b, _, "normal" mucosa, +, mild, ++, moderate, +++, marked; *, Comparison among the different grades, p < 0.01, **p < 0.001. The AI was also significantly higher in patients with intestinal metaplasia compared with those without metaplasia in the antrum (0.61 _+0.45 vs. 0.39 _+ 0.46) and incisura (0.67 _+ 0.41 vs 0.40 _+ 0.46) (both p < 0.05). CONCLUSIONS: Anti-H. pylori IgG antibodies are a predictive marker of the density of H. pylori colonization in the gastric body type mucosa but not antral type mucosa. This may indicate that an interaction between the organism and the gastric body epithelial cells is involved in the immune response. High IgG titers are associated with more severe and active gastritis in the whole stomach. • G1372 FAILURE OF HELICOBACTER PYLORI SEROLOGY TO IDENTIFY MOST PEPTIC ULCER DISEASE IN PATIENTS WITH DYSPEPSIA. HH-X Xia, J Kalantar, J Ma Wyatt, S Adams, K Cheung, H M Mitchell and NJ Talley. Departments of Medicine and Pathology, University of Sydney, Nepean Hospital, and School of Microbiology and Immunology, University of New South Wales, Australia BACKGROUND: Serological detection of H. pylori infection is sensitive and non-invasive and is a recommended screening test in dyspepsia to help to identify peptic ulcer. However, H. pylori infection is declining and there are increasing reports of H. pylori negative ulcers. We aimed to determine whether serology can still be used as a tool for screening patients with dyspepsia. METHODS: 209 patients (102 males and 107 females, average age 52.8 years) with upper gastrointestinal symptoms, but without previous anti- H. pylori therapy, were enrolled. 10 ml blood sample was obtained and a validated ELISA test was used to detect specific anti-H, pylori IgG antibodies (sensitivity 97% and specificity 96%). All patients were then independently endoscoped. RESULTS: 89 (43%) were seropositive for H. pylori infection. The prevalence was significantly higher in males than in females (52% vs. 34%, OR=2.2, p < 0.01, Z2-test), and in patients > 45 years than in those < 45 years (49% vs. 31%, OR=5.5, p < 0.02). At endoscopy, 42 (20%) were diagnosed as having peptic ulcer disease (PUD) (11 duodenal ulcer (Did), 27 (13%) gastric ulcer (GU) and four DU and GU), 77 (37%) gastroesophageal reflux disease (GERD), 88 (42%) non-ulcer dyspepsia (NUD) and two (1%) gastric cancer (GC). The value of a seropositive test in screening for peptic ulcer disease and gastric cancer applying different age cut-offs are shown in the table. GASTROENTEROLOGY Vol. 114, No. 4 Age Percentage(%)of seropositive patientsaccording to endosscopic findings* group (years) Peptic ulcer disease GC GERD NUD Total DU GU DU+GU Sub-total <34 100(2/2) 0(0/4) NA(0/0) 33(2/6) NA(0/0) 2(2/8) 28(5/18) 28(9/32) 35-44 50(1/2) 0(0/1) 0(0/1) 25(1/4) NA(0/0) 19(3/16) 53(8/15) 34(12/35) 45-54 50(1/2) 0(0/1) 0(0/1) 43(3/7) 100(1/1) 43(9/21) 57(12/21) 50(25150) >.55 80(4/5) 61(11/18) 50(1/2) 64(16/25) 100(1/1) 41(13/32) 41(14/34) 48(44/92) Total 73(8/11) 44(12127) 50(2/4) 52(22/42) 100(2/2) 35(27/77) 43(38/88) 43(89/209) *, seropositive number/case number in p~na~e~s, NA, notapplicable. Two patients with gastric cancer were seropositive. However, only 22 (52%) patients with PUD were positive; none of the six GU patients < 45 years were positive. Serology would have missed 9.5% (4/42) of peptic ulcer cases and saved 11% (23/209) in endoscopy workload when an age of 35 years was chosen as a threshold for indication of endoscopy. When an age of 45 or 55 years was chosen as the threshold, 22% (46/209) and 34% (71/209) of endoscopies would have been saved, respectively, but 17% (7/42) and 26% (11/42) of peptic ulcer cases would have been missed, respectively. CONCLUSIONS: Serology achieved a low detection rate for peptic ulcer disease in this population and 70% of patients with dyspepsia were 45 years or older; a strategy combining serology and an age threshold to reduce endoscopy workloads in Australia may be inappropriate. • G1373 THE RELATIONSHIP BETWEEN GERD AND OSAS AND EFFECTS OF ANTI-REFLUX THERAPY. GH Xiao, ZF Wang, MY Ke, XZ Huang.* Dept. of Gastroenterology and Dept. of Respiratory*, Peking Union Medical College Hospital, Beijing, 100730, China. Objective: The relationship between gastroesophageal reflux disease (GERD) and obstructive sleep apnea syndrome (OSAS) and effects of cisapride combined omprazole were evaluated. Subjects and Methods: 24-h esophageal pH and manometric monitoring and polysornnography (PSG) were performed on 18 patients [MIF=1711, mean age 44.4 yrs, range 27 ~ 58 yrs, body mass index (BMI) 20.6 ~ 33.3 kg/m2 (27.9 -+3.1kg/m2)] with snoring, daytime sleepiness and acid reflux, heartburn and regurgitation. Cisapride 10rag tid combined omprazole 20rag q12h was given patients with GERD and OSAS and 24-h esophageal pH and manometric monitoring and PSG was repeated on the 7th day. Results: (1) 7 of 18 patients with OSAS and severe GER were confirmed. These patients had daytime GER as well as nocturnal GER (All except one). (2) Nocturnal recordings were analyzed and found that pH below 4.0 were frequently followed by swallow (58.6%, control=20.6%, P<0.005), gross body movement (18.6%, control=4.8%, P<0.05) and arousal (26.8%, control=16.8%, P < 0.05). (3) The mean lowest esophageal pressure (- 15.2 _+ 9.6mmHg) before and (- 18.6 --. 10.1mmHg) after pH drops was significantly lower than during control periods (- 10.6_+ 8.1mmHg, P < 0.005) according to 432 numbers of GER. Then 24-h esophageal pH and manometric monitoring and PSG were repeated on the 7th day. (1) GER was significantly improved in all of these subjects. (2) There was also dramatically improved in total apnea time from 52.7 _+ 27.1 to 21.6_+21.2 minutes (P<0.002), Apnea hypopnea index (AHI) from 38.9 _+17.6 No./h to 15.2 _+12.3 No./h (P < 0.002), longest apnea time from 57.1 _+ 27.1 to 25.4 _+ 15.7 seconds (P < 0.002) except one patient. Conclusions: (1) There is significant association between GER and esophageal body pressure, apnea/hypopnea, gross body movement, swallow and arousal. (2) Cisapride combined omprazole was given one week and OSAS was dramatically improved as well as GER. Cisapride combined omeprazole becomes a new, simple and effective method on GER with OSAS. (3) GER is the predisposed factor to OSAS, both may coexist and affect each other. • G1374 HELICOBACTER PYLORI ANTIBODY RESPONSIVENESS AND PREVALENCE OF GASTRIC CANCER AMONG 10,000 CONSECUTIVE ENDOSCOPED JAPANESE INDIVIDUALS. Y Yamaji, H Ijichi, J Kato, T Ikenoue, S Maeda, K Ogura, M Okamoto, M Takahashi, H Yoshida, T Kawabe, Y Shiratori, N Toda*, H Ikuma*, K Nagatani*, K Yokouchi**, T Mitsushima**, and M Omata. Second Department of Internal Medicine, University of Tokyo, Tokyo; *Gastroenterology, Kameda General Hospital, Kamogawa; and **Makuhari Clinic, Chiba, JAPAN [Introduction] This study surveyed Over 10,000 of Japanese endoscoped population to investigate the relationship between Helicobacter pylori infection and gastric cancer. Special attention was given to the antibody titer. [Methods] We performed gastro-intestinal endoscopy and measured serum anti-H, pylori antibody simultaneously, to the consecutive 10,234 Japanese attending our health appraisal. Gastric cancer, when suspected, was confirmed by histology. We used GAP-IgG kit (Biomerica INC.), and graded the H. pylori antibody titer into three groups according to the OD values of ELISA, strongly positive, weakly positive, and negative. [Results] Among 10,234 subjects (male/female = 7021/3213, mean age = 49 _+ 9), 4909 (48%) were strongly positive, 1750 (17%) weakly positive, and 3575 (35%) negative for H. pylori antibody. Thirty-seven cases with gastric cancer were found among 10,234 subjects (the prevalence = 0.36%), 23/4909

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Page 1: The relationship between GERD and OSAS and effects of anti-reflux therapy

A336 AGA ABSTRACTS

• G1371 DOES HELICOBACTER PYLORI SEROLOGY PREDICT THE INTRAGASTRIC BACTERIAL DENSITY OF H. PYLORI AND THE HISTOLOGICAL SEVERITY OF GASTRITIS? HH-X Xia, J Kalantar, J Ma Wyatt, S Adams, K Cheung, H M Mitchell and NJ Talley. Departments of Medicine and Pathology, University of Sydney, Nepean Hospital, and School of Microbiology and Immunology, University of New South Wales, Australia

BACKGROUND: Serology has been established as a sensitive and specific technique for detecting H. pylori infection. However, whether the level of the IgG response is predictive of the bacterial density of H. pylori and the severity of the associated gastritis is unknown. The aim of this study was to determine the association between anti-H, pylori IgG antibody levels and bacterial density and severity of inflammation in the stomach. METHODS: 208 patients with dyspepsia were enrolled. Eight biopsies, ie. antrum (A) x3, body (B) x2, fundus (F) x2 and incisura (I) xl were taken from each patient during gastroscopy. One antral biopsy was used for the CLO-test. Three (one each from A, B and F) were cultured. The remaining biopsies were examined histologically according to the updated Sydney System after staining with H&E and Giemsa. A validated ELISA test was used to detect specific anti-H, pylori IgG antibodies and the absorbance index (AI) was applied to estimate the IgG titers. RESULTS: Overall, 84 patients (40%) were diagnosed as positive for H. pylori by CLO-test, histology and/or culture. The AI was significantly lower in the H. pylori negative patients than in positive patients (0.10 _+ 0.20 (mean _+ SD) vs 0.88 _+ 0.36, p < 0.001, t-tests). The associations of the AI with bacterial density and severity of gastritis at different gastric sites are shown in the table.

Absorbance index (mean) Gastric sites

Bacterial Densitv a Severity of Gastritis b Active Gastritis + ++ +++ - + ++ +++ Present Absent

Antrum 0.82 0.86 0.98 0.08 0.44 0 . 8 3 1.07"* 0.87 0.14"* Incisura 0.06 0.49 0 . 8 7 1.05"* 0.82 0.18"* Body 0.75 0.96 1.03"0.10 0.63 0 . 9 7 1.06"* 0.84 0.19"* Fundus 0.10 0.70 0.92 0.84** 0.81 0.27** a, includes the gastric antral-type and body-type mucosa of positive patients. +, small number, ++, moderate number, +++, large number; b, _, "normal" mucosa, +, mild, ++, moderate, +++, marked; *, Comparison among the different grades, p < 0.01, **p < 0.001.

The AI was also significantly higher in patients with intestinal metaplasia compared with those without metaplasia in the antrum (0.61 _+0.45 vs. 0.39 _+ 0.46) and incisura (0.67 _+ 0.41 vs 0.40 _+ 0.46) (both p < 0.05). CONCLUSIONS: Anti-H. pylori IgG antibodies are a predictive marker of the density of H. pylori colonization in the gastric body type mucosa but not antral type mucosa. This may indicate that an interaction between the organism and the gastric body epithelial cells is involved in the immune response. High IgG titers are associated with more severe and active gastritis in the whole stomach.

• G1372 FAILURE OF HELICOBACTER PYLORI SEROLOGY TO IDENTIFY MOST PEPTIC ULCER DISEASE IN PATIENTS WITH DYSPEPSIA. HH-X Xia, J Kalantar, J Ma Wyatt, S Adams, K Cheung, H M Mitchell and NJ Talley. Departments of Medicine and Pathology, University of Sydney, Nepean Hospital, and School of Microbiology and Immunology, University of New South Wales, Australia

BACKGROUND: Serological detection of H. pylori infection is sensitive and non-invasive and is a recommended screening test in dyspepsia to help to identify peptic ulcer. However, H. pylori infection is declining and there are increasing reports of H. pylori negative ulcers. We aimed to determine whether serology can still be used as a tool for screening patients with dyspepsia. METHODS: 209 patients (102 males and 107 females, average age 52.8 years) with upper gastrointestinal symptoms, but without previous anti- H. pylori therapy, were enrolled. 10 ml blood sample was obtained and a validated ELISA test was used to detect specific anti-H, pylori IgG antibodies (sensitivity 97% and specificity 96%). All patients were then independently endoscoped. RESULTS: 89 (43%) were seropositive for H. pylori infection. The prevalence was significantly higher in males than in females (52% vs. 34%, OR=2.2, p < 0.01, Z2-test), and in patients > 45 years than in those < 45 years (49% vs. 31%, OR=5.5, p < 0.02). At endoscopy, 42 (20%) were diagnosed as having peptic ulcer disease (PUD) (11 duodenal ulcer (Did), 27 (13%) gastric ulcer (GU) and four DU and GU), 77 (37%) gastroesophageal reflux disease (GERD), 88 (42%) non-ulcer dyspepsia (NUD) and two (1%) gastric cancer (GC). The value of a seropositive test in screening for peptic ulcer disease and gastric cancer applying different age cut-offs are shown in the table.

GASTROENTEROLOGY Vol. 114, No. 4

Age Percentage (%) of seropositive patients according to endosscopic findings* group (years) Peptic ulcer disease GC GERD NUD Total

DU GU DU+GU Sub-total <34 100(2/2) 0(0/4) NA(0/0) 33(2/6) NA(0/0) 2(2/8) 28(5/18) 28(9/32) 35-44 50(1/2) 0(0/1) 0(0/1) 25(1/4) NA(0/0) 19(3/16) 53(8/15) 34(12/35) 45-54 50(1/2) 0(0/1) 0(0/1) 43(3/7) 100(1/1) 43(9/21) 57(12/21) 50(25150) >.55 80(4/5) 61(11/18) 50(1/2) 64(16/25) 100(1/1) 41(13/32) 41(14/34) 48(44/92) Total 73(8/11) 44(12127) 50(2/4) 52(22/42) 100(2/2) 35(27/77) 43(38/88) 43(89/209) *, seropositive number/case number in p~na~e~s, NA, not applicable.

Two patients with gastric cancer were seropositive. However, only 22 (52%) patients with PUD were positive; none of the six GU patients < 45 years were positive. Serology would have missed 9.5% (4/42) of peptic ulcer cases and saved 11% (23/209) in endoscopy workload when an age of 35 years was chosen as a threshold for indication of endoscopy. When an age of 45 or 55 years was chosen as the threshold, 22% (46/209) and 34% (71/209) of endoscopies would have been saved, respectively, but 17% (7/42) and 26% (11/42) of peptic ulcer cases would have been missed, respectively. CONCLUSIONS: Serology achieved a low detection rate for peptic ulcer disease in this population and 70% of patients with dyspepsia were 45 years or older; a strategy combining serology and an age threshold to reduce endoscopy workloads in Australia may be inappropriate.

• G1373 THE RELATIONSHIP BETWEEN GERD AND OSAS AND EFFECTS OF ANTI-REFLUX THERAPY. GH Xiao, ZF Wang, MY Ke, XZ Huang.* Dept. of Gastroenterology and Dept. of Respiratory*, Peking Union Medical College Hospital, Beijing, 100730, China.

Objective: The relationship between gastroesophageal reflux disease (GERD) and obstructive sleep apnea syndrome (OSAS) and effects of cisapride combined omprazole were evaluated. Subjects and Methods: 24-h esophageal pH and manometric monitoring and polysornnography (PSG) were performed on 18 patients [MIF=1711, mean age 44.4 yrs, range 27 ~ 58 yrs, body mass index (BMI) 20.6 ~ 33.3 kg/m 2 (27.9 -+ 3.1kg/m2)] with snoring, daytime sleepiness and acid reflux, heartburn and regurgitation. Cisapride 10rag tid combined omprazole 20rag q12h was given patients with GERD and OSAS and 24-h esophageal pH and manometric monitoring and PSG was repeated on the 7th day. Results: (1) 7 of 18 patients with OSAS and severe GER were confirmed. These patients had daytime GER as well as nocturnal GER (All except one). (2) Nocturnal recordings were analyzed and found that pH below 4.0 were frequently followed by swallow (58.6%, control=20.6%, P<0.005), gross body movement (18.6%, control=4.8%, P<0.05) and arousal (26.8%, control=16.8%, P < 0.05). (3) The mean lowest esophageal pressure (- 15.2 _+ 9.6mmHg) before and (- 18.6 --. 10.1mmHg) after pH drops was significantly lower than during control periods (- 10.6_+ 8.1mmHg, P < 0.005) according to 432 numbers of GER. Then 24-h esophageal pH and manometric monitoring and PSG were repeated on the 7th day. (1) GER was significantly improved in all of these subjects. (2) There was also dramatically improved in total apnea time from 52.7 _+ 27.1 to 21.6_+21.2 minutes (P<0.002), Apnea hypopnea index (AHI) from 38.9 _+ 17.6 No./h to 15.2 _+ 12.3 No./h (P < 0.002), longest apnea time from 57.1 _+ 27.1 to 25.4 _+ 15.7 seconds (P < 0.002) except one patient. Conclusions: (1) There is significant association between GER and esophageal body pressure, apnea/hypopnea, gross body movement, swallow and arousal. (2) Cisapride combined omprazole was given one week and OSAS was dramatically improved as well as GER. Cisapride combined omeprazole becomes a new, simple and effective method on GER with OSAS. (3) GER is the predisposed factor to OSAS, both may coexist and affect each other.

• G1374 HELICOBACTER PYLORI ANTIBODY RESPONSIVENESS AND PREVALENCE OF GASTRIC CANCER A M O N G 10,000 CONSECUTIVE ENDOSCOPED JAPANESE INDIVIDUALS. Y Yamaji, H Ijichi, J Kato, T Ikenoue, S Maeda, K Ogura, M Okamoto, M Takahashi, H Yoshida, T Kawabe, Y Shiratori, N Toda*, H Ikuma*, K Nagatani*, K Yokouchi**, T Mitsushima**, and M Omata. Second Department of Internal Medicine, University of Tokyo, Tokyo; *Gastroenterology, Kameda General Hospital, Kamogawa; and **Makuhari Clinic, Chiba, JAPAN

[Introduction] This study surveyed Over 10,000 of Japanese endoscoped population to investigate the relationship between Helicobacter pylori infection and gastric cancer. Special attention was given to the antibody titer. [Methods] We performed gastro-intestinal endoscopy and measured serum anti-H, pylori antibody simultaneously, to the consecutive 10,234 Japanese attending our health appraisal. Gastric cancer, when suspected, was confirmed by histology. We used GAP-IgG kit (Biomerica INC.), and graded the H. pylori antibody titer into three groups according to the OD values of ELISA, strongly positive, weakly positive, and negative. [Results] Among 10,234 subjects (male/female = 7021/3213, mean age = 49 _+ 9), 4909 (48%) were strongly positive, 1750 (17%) weakly positive, and 3575 (35%) negative for H. pylori antibody. Thirty-seven cases with gastric cancer were found among 10,234 subjects (the prevalence = 0.36%), 23/4909