631

Screening for Coiorectal Cancer: Direct Comparison of a Brush-Sampling Fecal Immunochemical Test for Hemoglobin with Hemoccuh Stephen Cole, Alicia Smith, Peter Bampton, Jayne Sandford, Joylene Morcom, Graeme P. Young

Background: Newer fecal occult blood tests (FOBT) incorporating immunochemical technol- ogy reduce barriers to population screening for colorectal cancer by removing need for dietary or drug restrictions (Cole Set al, Med J Aust 2001;175:195). !nSure | is a new fecal immunocbemical test (FIT) that requires just 2 stool samples that are collected using a simple brush. However, performance characteristics of this novel FIT have not been deter- mined relative to a guaiac FOBT. Aim: To compare performance of the guaiac FOBT (Hemoccult TM ll Sensar~; HO) with the novel FIT, !nSure, in various settings where colonos- copy was subsequently performed. Methods: Patients sampled consecutive stools with both !nSure and HO sampling devices while following dietary restrictions appropriate for HO. !nSure samples were taken from 2 separate stools immersed in toilet bowl water using a brush, while HO samples were taken from 3 stools using a spatula. Patient populations were: an average risk screening cohort (n = 284, median age 67, range 56-74), a high risk surveillance cohort (n= 158, median age 65, range 34-86) and a symptomatic diagnostic group (n = 18, median age 63, range 40-82). Outcome measures: Sensitivity for cancer, for cancer plus adenomas -> 10ram (significant neop[asia) or for cancer plus all adenomas (all neoplasla); positive predictive value (PPV); false positive rate (FPR); tests compared by paired 2x2 tests (with 95% confidence interval (CI) of difference) or g2. Results: !nSure was sigmficanfly better at detecting cancers, significant neoplasia or all neoplasm (see Table for sensitivity for prevalent lesions). PPVs (for all neoplasia) were not significantly different: !nSure 30/69 (43.5%), HO 21/61 (34.4%), X 2= 2.11 p=0.29. FPR (for all neoplasia) were similar: !nSure 15/344 (4.4%), HO 14/344 (4.1%). Conclusions: !nSure provides significantly better sensitivity for co[orectal neoplasia without any loss of specificity when compared to HO. Combined with its novel and simpler sampling plus the ability of FIT technology to reduce barriers to screening, !nSure represents an improved alternative to Hemoccult Sensa for screening.

Tests Cancers SIRnlflcant neolflallia All neoplasia InSure 11/13 (84,6%) 17/22 (77.3%) 30/44 (68,2%) Flemocc=lt Senu 5/13 (38.5%) 11/22 (50%) 22/44 (50%) 95% CI of dlffereoce 12.0%-64.9% 4,8%-49,7% 1.2%-35.2%

635

Relation between Partial Gastric Volumes and Upper Gastrointestinal Sensations in Patients with Functional Dyspepsia and Healthy Volunteers Measured with 3- Dimensional Ultrasonography Marco W. Mundt, Andre J. P. Smout, Melvin Samsom

3D ultrasound is a non-invasive techmque to measure gastric volume. Aim of this study was to investigate the relation between total and partial gastric volume changes and sensations in patients with functional dyspepsia and healthy volunteers. METHODS: 12 patients with functional dyspepsia (5 male, age 40.7 + _ 14, range 21-69) and 15 healthy volunteers (6 male, age 26.8 + - 7, range 20-39) participated. 2D ultrasonographic images of the total stomach were acquired during a sweep (approximately 300 images within 20 sec). A pulse- magnetic field generator and a probe sensor enabled 3D orientation. Sensations (epigastric pain, fullness, nausea, and hunger) were scored using a VAS. Subjects ingested a 500 ml liquid meal (200 ml Nutridrink + 300 ml water, 300 kCal) within 3 rain. Data were acquired at t = 0 and 5, 15, 30, 45, 60 min postprandially. The gastric wall was outlined manually using 3D analysis software and total gastric volume was calculated, subsequently proximal gastric volume (10 cm downward from diaphragm) and distal gastric volume (between pyloms and antral area landmarks) were calculated from total 3D gastric volumes. Relationships were assessed using partial correlation, controlling for subjects. RESULTS: Mean fasting gastric volume in patients (37.0 +- 7.7 ml) was comparable to healthy volunteers (32.5 +- 2.5 ml, p = NS). In addition, no differences in gastric volume were observed 5 rain postprandially (506.7+-6.9 nfl vs. 494.6+-6.4 ml, p=NS) and gastric volume linearly decreased during the first postprandial hour. The increase in total gastric volume was related to the increase in fullness, both in patients (r=0.47, p<0.O01) and healthy volunteers (r= 0.53, p<O 001). This relationship appeared to be caused by the distal stomach since an even stronger correlation between increase in distal gastric volume and increase in fullness and hunger could be observed in patients (r =0.74, p<0.001, r-0.36, p = 0.007) as well as in healthy volunteers (r = 0 79, p<0.001, r =0.34, p =0.003). In contrast, no relation was found between the increase in proximal volume and the increase in fullness and hunger in patients (r=0.19, r-0.O01, p=NS) and healthy volunteers (r=0.18, r-0.09, p=NS) Conclusion: The distal stomach rather than the proximal stomach plays the key role in the generation of the upper gastrointestinal sensation fullness and hunger in patients with functional dyspepsia as well as in healthy volunteers.

636

Effect of Acid Perfusion of Duodenum on Induction of Dyspeptic Symptoms in Healthy Volunteers Michele Di Stefano, Rita Vos, Jozef Janssens, Jan F. Tack

Background and Aims: Recently, we reported increased duodenal acid exposure associated with increased symptom severity in a subset of functional dyspepsia (FD) patients (Lee, 2002), but its pathogenetic role is still unclear. To evaluate involvement of duodenal acid exposure in symptom generation, we induced a hyperacidity status of the duodenum in healthy volunteers (HV) and assessed its influence on symptoms. Patients and Methods: Nine HV (4m, 22-33 yrs) underwent 2 studies. After an overnight fast, a 7-channel water- perfnsed catheter, an infusion catheter and a pH probe were positioned under fluoroscopic control: the most distal manometric channel was placed after Treitz ligament, 2 channels

in duodenum, 4 in antropyloric region; perfnsion and pH probe were in the second duode- num. After a phase Ill of the MMC was recorded, acid solution (pH 2) or saline in a double blind, randomized, crossover protocol was perfused at a rate of 5ml/min. After 30 rain, subjects ate a meal (one egg, two slices of bread, 150 cc of water) and motility registration continued for a further 5-hour period. During fasting and every 15 minutes after the meal, severity of discomfort, fullness, bloating, belching, nausea, heartburn, epigastric burning, satiety and pain were evaluated by visual analog scale. Mean duodenal acid exposure (% time pH<4) in 15-rain periods was also evaluated. Results: During acid perfusion, symptom scores for discomfort, bloating, nausea, eplgastric bummg were significantly higher (p<0.01) compared to saline. Postprandial antral MI was lower (2.96 • 1.8 vs 3.62 + 1.8, p = 0.01) and jejunal MI higher (4.87 + 1.0 vs 4.37 -+ 1.4, p = 0.01) during acid per fusion. Occurrence and duration of phases Ill showed no difference. Conclusions: Duodenal acid perfnsion induces antral hypomorility, jejunal hypercontractflity and causes a sensitization to dyspeptic symptoms. Through these mechanisms, increased duodenal acid exposure may play a role in the pathophysiology of FD symptoms

637

G-Protein Mediated Receptor-Cell-Coupling as a Predictor for the Long Term Response to Treatment in Patients with Functional Dyspepsia Gerald Holtmann, Winfried Siffert, Elisabeth Grote, Sebastian Haag, Ute Braun-Lang, Mathias Langkafel, Nicholas Talley

Background: Very little is known regarding factors that influence the long term outcome of patients with functional dyspepsia. G-proteins are essential for stimulus-response coupling of receptors which are linked to intracellular effector systems such as the adenylcyclases, the phosphoinositide system, ion channels, as well as various protein kinases and transcription factors. Thus polymorphisms of specific G-protein may influence functions that are linked to the development of symptoms. Aims: To study the role G-protein protein GNB3 for the long term outcome of FD patients adjusting for symptom pattern and concomitant psychiatric disturbances. Methods: We recruited 80 patients with chronic or relapsing symptoms (> 5 years) that were referred to a tertiary referral center for evaluation and treatment of non- responsive symptoms. All patients had predominantly upper abdominal symptoms with the final diagnosis of functional dyspepsia after extensive diagnostic work up. Presence of anmety and depressive disorders were clinically judged by a trained physician. Genomic DNA was isolated from buccal swabs and genotyping of the C825T/C polymorphisms was performed by PCR and restriction analysis. All patients were treated based upon the predominant symptom pattern utilizing PPI, prokinetics, spasmolytics and low does tricyclic antidepres- sants as indicated. In addition, most patients received behavinural and relaxation therapy. After 12 month patients were categorized based upon their judgment as respond, ers ( complete or sufficient relief of symptoms) or non responders ( ~ only moderate improvement, no change or deterioration of symptoms). Results: After 12 month 23 out of 80 patients were categorized as responders (R + ) while 57 patients were categorized as non-responders (NR). The GNB3 CC polymorphism was found in 56 % of patients and was univariately associated with R + (p<0.02), while dysmotility-type (p<0.02), concomitant IBS-symptoms (p<:0.05) and the presence of an anxiety disorders (p<005) were associated with NR. Logistic regression analysis revealed a signtficant (p<0.05) association between the R+ arid the CC polymorphisms while there was a trend for a negative association between dysmotility- symptoms. Conclusions: Molecular variants of the GNB3 that modulate receptor cell-cou- pling, influence outcome and response to medical therapy in functional dyspepsia.

638

Functional Dyspepsia : Cholinergic or Nitrergic Disorder? Mickael Bouin, France Lupien, Pierre Poitras

Background : In patients with functional dyspepsia (FD), tolerance to gastric fundus disten- sion is frequently compromised. Based upon the fact that acetylcholine and nitric oxide (NO) are major contributors in balance for respectively the contraction and the relaxation of the stomach fundus, we tested the contribution of the cholinergic or nitrergic pathways in this disorder. Methods : FD patients with impaired tolerance (i.e. maximum tolerated volume less than 600 ml of distension as found in normal healthy volunteers) to gastric distension were included in this study. Gastric distension studies where done by inflating a fundic balloon with progressive amount of air until the maximum tolerated volume of distension was reached by the patient. Gastric distension was first evaluated in basal control conditions before repeating the test after the injection of the anticholinergic hyoscine (Busco- pan 20 rag IV) or following the administration of NO donor nitroglycerin (Nitrolingual 1.2 mg sl). Results : 11 patients were included in both treatment groups. Hyoscine improved tolerance to gastric balloon distension in 73% of patients (from 459 +A 28 ml to 595 +/- 48 nil; p < 0.01). Nitroglycerin was effective in only 9% of the patients (409 +/- 38 rnl to 431 +/- 44 ml; ns); when hyoscine was added in nitroglycerin non responsive patients, tolerance to distension was then improved in 75% of the cases (418 +/- 40 ml to 556 +/- 58 ml; p < 0.01). Conclusion : Under these experimental conditions, the cholinergic rather than the nitrergic pathway seem to be a predominant factor involved in the tolerance to distension in patients with functional dyspepsia

639

Paradoxical Effect of Helicobacter pylori Infection on Epigastric Pain and Hear tburn in Subjects Taking NSAIDs or Aspirin: the Bristol Helicobacter Project Anne McCune, Richard Harvey, Athene Lane, Liam Murray, lan Harvey, Prakash Nair, Jenny Donovan

Background: Helicobacter pylori and non-steroidal anti-inflammatory drugs (NSAIDs) are the most important causes of peptic ulcer disease. We have studied the interaction of H.pylor/ infection with dyspeptic symptoms in subjects taking NSAIDs or aspirin. Methods: The Bristol Helicobacter project is a large community-based prospective randomised controlled

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