ECL cell origin of gastric carcinomas not only in rodents, but also in man

and a 24-hr pH monitoring study was nl in 2/2 patients. The only endoscopic abnormalities noted were multiple rings (4), and a post-dilatation superficial tear (1), whereas the others were normal; no patient had endoscopicfindings to suggest GERD.All patients had esophageal dilatations at least once (ten times in 1 patient) without sustained improvement. A close review of the endoscopic biopsies demonstrated the intense eosinophilic infiltration (>20/ hpf), highly suggestive of eosinophilic esophagitis. Three patients have completed a 6-week course of steroid lavage,with complete resolution of symptoms, and clearanceof the eosinophilic infiltration. Conclusion: A diagnosis of eosinophilic esophagitis should be suspectedin unresponsive patients treated for GERD. Clinicopathologiccorrelations are important: these patients present with obstructive symptoms (dysphagia, food impaction) and have dense eosinophilic infiltration of the esophagus (>20/hpf). 1302 The Gastritis Phenotype in Gastric Ulcer (GU) Is Not Corpus Predominant. Observations from the Byk Advanced Gastric Ulcer Study (BAGUS) Before and After Eradication Peter Malfertheiner, Otto yon Guericke Univ, Magdeburg Germany; Manfred Kist, tnst fuer Mikrebiologie and Hygiene, Freiburg Germany; Thomas Kirchner, PathologischesInst der Univ, Erlangen Germany; Ulrich Peitz, Otto von Guericke Univ, Magdeburg Germany; Martina Bohuschke, Byk Gulden GmbH, KonstanzGermany; Sonja Strebel, Inst fuer Mikrobiologie und Hygiene, Freiburg Germany;, and the BAGUS study group Objective:Contraryto DU in GU the phenotypicexpressionof gastritis is reportedto be corpus (C) predominant, however, data in GU are based on studies with only small patient numbers. Basedon the largest trial in GU to date (BAGUS)we investigatedthe efficacy of pantoprazolebased triple therapy on the eradicationof H. pylori (HP) and also the pattern of gastritis prior to and 4 weeks alter treatment. Methods: Data of 464 patients (IH) with the mean age of 57_+13 years and a m/f ratio of 1.3 were analysed. Biopsies form antrum were taken 2 to 4 cm prepyloric at the greater and lesser curvature, from corpus ca 4 cm proximal of the angulus and from the greater curvature ca. 8 cm from the cardia. Malignancy of the tissue was determined from additional biopsies of the GU. Scores (updated Sydney classification) on a 4-point scale: none (0), mild (1), moderate (2), severe (4) were built for HP density, signs of active and chronic inflammation, and atrophy. Intestinal metaplasia(IM) was categorised (none, incomplete, complete) and analysed quantitatively. Results: HP density in the antrum and the corpus was similar. Howeverthe density of granulocyteand lymphoplasmacellular infiltrates as well as of lymphatic follicles/aggregateswere more prominent in the antrum than in the corpus. After 4 week's therapy the signs of active inflammation were markedly reducedin the antrum (1,82 to 0,17) and the corpus (1,39 to 0,14). The density of lymphoplasmacellular infiltrates also decreased(antrum:2,09 to 1,41; corpus: 1,59 to 1,07), but not to normal.The percentageof IM (34% vs. 9.5%) and the score for atrophy was more prominent in the antrum than in the corpus, which both did not change after therapy. Conclusion:The gastritis pattern of GU is only slightly different than that of DU. Although the HP density in the corpus was comparablethe antrum the active and chronic inflammatory response was tendentially lower in the corpus. Therefore additional factors beside the HP density may play a role in the modulation of gastritis in GO. Active inflammation is reversedto normal and the chronic infiltrates decreasedmarkedly already 4 weeks following HP eradication.

1304 The Assessment of EsophagogastroduodenoscopyTolerance; a Prospective Study of 300 Cases Ashkan Farhadi, Rush Univ, Chicago, IL

Background..Esophagogastroduodenoscopy(EGD)is one of the most useful diagnostic procedures in the evaluation of dyspepsia. Patient preference is a major determinant in physician decision-making to use EGD as a diagnostic procedure. Methods: We have prospectively evaluated 300 cases from several aspects, prior, during and after an EGD procedure to find out the parametersthat determineor influence EGDtolerance in non sedatedpatients. Results: We have gatheredfrom the patient's standpoint that 79% had good EGDtolerance. Comparing the patient's perception of EGD tolerance with other parametersthat indirectly imply to EGD tolerance [e.g., ease of entubation; patient's cooperation during the endoscopic procedure (physician's point of view of EGD tolerance); number and severity of retching episodes], we noted that these parameters significantly correlated with the patient's perception of EGD tolerance. We subsequentlyevaluatedthe parametersthat influenced EGD tolerance. From all of those parametersthat were evaluatedin our cases only age and patient's gagging during Lidocainethroat sprayingsignificantly correlated with the patient'sperceptionof EGDtolerance. On the other hand, we did not find any significant correlation between EGO tolerance and parameters such as sex, education level, body hahitus (obesity), fear or anxiety about the procedure, or procedure type and duration. Conclusions: Our data suggest that 1) Several parameters (e.g., retching No) could be used interchangaablywith patient's perception of EGOtolerance;2) age and patient's gagging during Lidocainethroat spraying, but not patient's fear and anxietyabout the procedure,are good indicatorsfor predicting EGOtolerance; 3)using these indecies one might be able to appropriately select patients for sedation. Patient'sPerceptionof EGDTolerancevs. PhysicianStandpointof EGDTolerance

Patients Perception Good Patient'sPerception Poor Total

Physician'sview Good_

Physician'sview _Poor

_Total

196 (83%)

_40 (17%)

236(79%)

19 (29%)

_45 (71%)

_64 (21%)

_215(73%)

_85 (28%)

_300

(:;hi Squares= T0.42 P < 0.00001 1305 High Dose IV PPI Is Less Costly than Standard Medical Management for Preventing Acute Recurrence of Peptic Ulcer Hemorrhage (PUH) after EndoscopicTherapy (ET) - A Cost-Minimization Analysis. Virender K. Sharma, Univ of Arkansas for Medical Science, Little Rock, AR; Colin W. Howden, Northwestern Univ, Chicago, IL Background: High dose iV PPI has been reported to prevent acute PUH recurrence after ET. The cost saving of this approach has not been established.Aim: Using a decision-basedcostminimization analysis, to establish the cost saving of high dose IV PPI after ET in patients with PUH. Methods: A decision model was constructed to compare PUH-relatedhospi~l costs in patients with PUH requiring ET and then given high dose IV PPI or standard medical therapy. The probabilities(rangefor sensitivity analysis)of developingan acute PUH recurrence with high dose iV PPI and standard therapy were 15 % (5-25%)and 25% (15-40%), respectively. The probability of death from a rebleedwas 10% (5-15%). 80% (70-90%) of rehleeds were managedendoscopicallyand 10% (5-15%) required surgery. The probability of hemostasis with repeat El" was 50% (30-70%); endoscopic failures required surgery. Hospital costs (range for sensitivity analysis) used were: high dose IV PPI $100 / day ($20-200) and oral PPI $2.50 ($1-5), ET $250 ($100-500), surgery $5000 ($1000-10,000), ICU stay $2000 / day ($500-5000) and general ward stay $1000 / day ($500-1500). Results: Costs of treatment with high dose IV PPI and standard medical therapy were $10,215 / patient and $10,950 / patient,respectively.Comparedto standard therapy, high dose IV PPI resulted in a saving of $ 735/patient. One-way sensitivity analysis indicated that high dose IV PPI cost less than standard medicaltherapyfor all costs and probabilitiestested, exceptprobability of re-bleeding in the two strategies.At probability of re-bleedingof < 18% with standard therapy or >22% with high dose IV PPI, standard medical therapy became cheaper. Conclusions: High dose IV PPI after ET is cheaperthan conventionaltherapy for preventing acute recurrence of PUll. Patients with PUH who require ET should receive high dose IV PPI for at least 72 hours.

1303 Prevalence of the Inguinal Hernia in the Patients with Hiatal Hernia. Leonardo De Luca, Pietro Di Giorgio, Enrico Sorrentino, Bruno De Lusa, Pellegrini Hosp, Napoli italy; Joseph A. Murray, Mayo Ciin, Rochester, MN BACKGROUND:Hiatal hernia (HH) is an important risk factor in severe esophagitis. There have been many theories as to why hiatal hernias develop.The so called "Pull" and "Push" theories havebeenput forward. Inguinalhernias(IH) are a common herniation of the abdominal wall that is usually readily evident on physical examination. If hiatal hernias are caused by an excess "Push" from increased intra-abdominal pressure then we hypothesizedthat there would be a greaterthan by chanceassociation betweenHH and IH. The aim of this prospective sase-contrel study was to determinethe prevalenceof IH in the patients (pts) with HH (group A) compared to those without HH (group B) identified at endoscopy. METHODS:From 1/99 to 12/99, consecutive adults, who were referred for elective upper GI endoscopies in the Endoscopic Unit, were evaluated. Data was collected regarding gender, age, BMI, presence or absence of HH, length of HH and the presence of IH, prior surgery for [H on detailed abdominalexaminationof eachsubject by one examiner(LDL). HH was definedas the presence of at leastone cm of stomach abovethe diaphragmaticimpression.HH length was measuredas the distancefrom the EGJ,the proximal extent of the vertical gastric folds, to the diaphragmatic impression on the stomach. The width of the hiatal openingthrough the diaphragmaticopening was confirmed by viewing the cardia 1rum below. Statisticat analysis study was performed using the two-tailed Z test for comparison of proportions. A p-value less than 0.05 was considered significant. RESULTS:559 (316:243 - males:females,averageage 48.8, average BMI 25.1) consecutive out-patients were enrolled in this study. Of these pts, 128 (23%) (61:67 - males:females,averageage 52.9, averageBMI 25.3) had HH (group A). 431 pts did not have HH (group B: 255:176 - males:females, averageage 47.6, average BMI 25). The average length of the HH was 2.7 cm (range 1.5 - 6). The IH prevalencein the group A was of 13% (17/128) comparedto that in those without HH group B 5.5% (24/431). Obesity was not associatedwith a greater risk of HH in these pts. CONCLUSIONS:The prevalenceof the IH in the pts who have an HH is greater than in those without HH. Obesity did not correlate with the presenceof HH or IH. This might suggest that a connectivetissue defect in response to chronically or intermittent increasedintra-abdominal pressure (Push) is a factor in at least some pts with HH or IH. However,obesitydoes not appearto be a risk factor in the development of these hernias in this Southern Italian population.

1306 ECL Cell Origin of Gastric Carcinomas Not Only in Rodents, but Also in Man Helga L. Waldum, Gunnar Qvigstad, Arne K. Sandvik, NTNU, Faculty of Medicine, Trondheim Norway BACKGROUND:Although the stomach and the lungs have a common embryological origin (foregut), neuroendocrineorigin of gastric carcinomashas in contrast to bronchial carcinomas been consideredto be rare. However,the distinction betweennon-endocrineadenocarcinomas and neuroendocrinecarcinomasmay be difficult. Thus, the malignantgastric tumors occurring spontaneously in mastomys, and those after life-long dosing with proton pump inhibitors in rats, were initially classified as adenosarcinomas, and only subsequently reclassified as neuroendocrine and more specifically of ECL cell origin. METHOD: We therefore examined malignant gastric tumors occurring spontaneously in cotton rats and gastric carcinomas in man, for neuroendocrine and more specifically ECL cell differentiation using immunohistochemical and histochemical (Sevier-Mungar silver staining) methods as well as different methodsto detect geneexpressionspecific for neroendocrineand more specifically ECLcells. We also applied tyramide signal amplification (TSA) of immunohistochemistry to improve sensitivity without reducing specificity. RESULTS: By conventionat immunohistochemical

A-251

examinationwe could show that malignanttumors in cotton rats were neuroendocrine(chromogranin A immunoreactive) and more specifically ECL cell derived (hietidine decarboxylase immunoreactive and Sevier-Mungerpositive). Moreover, a substantial part of gastric carcinomas from man and especially those classified as diffuse according to Lauren, expressed markers compatiblewith neuroendocrine(chromogranin A), and more specifically of ECL cell (Sevier-Munger) origin. Whereasthe number of positive tumor cells were low in most carcinomas studied by conventional immunohistochemical reaction, the number of positive cells increased markedly when applying the tyramide signal amplification for the chromngranin A immunoitetection. CONCLUSION:ECLceils give rise to gastric carcinomasnot only in rodents, but also in man. 1307 Evaluation Of Flash Echo Imaging For Assessment Of Blood Pertuzioe in Gastric Cancer Hideharu Okanohu, Jiro Hata, Ken Haruma, Mutsunori Hara, Kenjiro Nakamura, Koji Futagami, Shunji Matsumura, Shigeto Yoshida, Hiroaki Kusunoki, Shinji Tanaka, Masaharu Yoshihara, KazuakiChayama,Hiroshima Univ Sch of Medicine, Hiroshima Japan BACKGROUND:We have reported the usefulness of the Flash Echo Imaging (FEI) which is the intermittent harmonic imaging under the administration of microbubble contrast agent (Levovist), as the non-invasive method for the assessment of gastric blood flow in vivo (Gastroenterology A475, 2000). The AIM of this study was to confirm the reliability of FEI for the assessment of blood perfusion in gastric cancer by comparing with tumor vessel densities of the resectedspecimens. PATIENTSAND METHODS:Ten patients with advancedstage of gastric cancer (6 men, 4 women) were enrolled in this study. FEI was performed .beforegastrectomyas previously reported. On the tumor image of the strongest enhancement in each FEI series, 5 range of interest was settled to decide the mean echo intensity of the tumor. The mean tumor vessel densities were decided by counting microveseel on 5 fields (400x) of CD34-stainedspecimens. RESULTS:As shown in Fig.l, a significant positive linear correlation was noted between the intensity of FEI and microveseel count in CD34 stained specimens (r2 = 0.889, P
r~. t t4 13

Utilization Of IV Ranitidine And IV Pantoprazole in The Intensive Care Unit Of A University Teaching Centre David G. Morgan, Ajay Jain, McMaster Univ, Hamilton Canada;Catherine 8ednarowski, Hamilton Health Science Corp, Hamilton Canada Ajay Jaid, David Morgan~, Catherine Bednarowski2. Divisions of Gastroenterology~and Pharmacy~, McMaster Univers~ and Hamilton Health Sciences Corporation, Hamilton, Ontario, Canada Aim: in intensive care unit (leO) patients at a University teaching hospifal to: (1) compare the utilization of IV Ranitidine (R) before and alter the release of IV Pantoprazole (P) and; (2) evaluatethe utilization and dosing regime of P (bolus [8] vs continuous infusion [I]). Background: In the ICU, clinically significant stress-ulcer related bleeding results in significant morbidity and mortality. H2-reeeptorantagonists are commonly used for stressulcer prophylaxis. Who needsto be treated and with what is still debated.There is little data examiningthe utilization of proton-pump inhibitors in an ICU setting. Methods: Retrospective review identifying the number of ICU patients and the number of treatment days for R between May 1998 and April 1999 (Period 1) and; R and/or P between May 1999 and April 2000 (Period 2). Data was extractedfrom hospital computerizedpharmacy records. Results: R was administered in doses of 50rag 00, 50rag BID, or 50mg TID. P in its bolus form was given in doses of 40rag 00, 40rag BID, or 80rag 00; and as a continuous infusion in doses of 4mg/hr or 8rag/fir. There was a reduction in the utilization of R between Period 1 (612 days for 83 patients; 9.71 days/pt) and Pedod 2 (417 days for 56 patients; 7.44 days/pt). This difference was attributed to the use of P (285 days for 22 patients; 12.95 days/pt). During Period 2, the use of P compared with R was significantly greater (p = 0.027). Of the 285 day utilization of P, 240 days (22 patients; 10.91 days/pt) was administered as B; and 45 days (6 patients; 7.5 days/pt) as I (p = 0.05). Of the six patients that received continuous infusion P, all were used for presumed upper gastrointestinal bleeding.The approximatecost ($CDN) associated with the use of R was $3176.28 during Period 1, and during Period 2, $2164.23. The approximate total cost of P during Period 2 was $9658.50 (B - $6576.00). Conclusion: Sincethe releaseof IV Pantoprazole,the utilization of IV Ranitidinein ICU patients has been reduced. The majority of patients received P as a bolus. The number of days of use of I, P was greater than the suggested dosing for upper gastrointestinal bleeding (7.5 days vs 3.0 days). The implementation of educationaland managementguidelines in the use of R and P will result in more appropriate utilization and cost savings.

0

,;-=-ore9 ~,< oJooJ,

~12 ~,ro

1309

1311 o

Bolullmim To=in Injection and Surgical Crico-Myotomyfor Oro-Phawngeai OysPha8ia: Pvelimiiary Results of a Phase-II Study. Marie Costantini, Giovanni 7.aninotto, Rosario Marchese Ragona, Marco Ferraro, ChJara Briani, Lie Zanetti, Giorgio Rosa, GiusappePortale, Michela Costantino, Univ of Padua, Padua Italy

7 6 ~

40

i

i

.50

60

, 70

i 80

i 90

i Lno

II0

mlcrovessel densit), (counzs/field)

1308 Application of Blood Levels of Gastrin-17, Pepsinooos I and H.pylori Antibodyfor NoneodoscopicDiagnosis of Atrophic Gastritis Pentti Sipponen, Tiina Maki, Paivi Ranta, Jorvi Hosp, Espoo Finland; Auli Linnala, 8iohit PIc, Helsinki Finland; Ilpo Keariainen,Titan Helske, Jorvi Hosp, Espoo Finland; Osmo Suovaniemi, 8iohit PIc, Helsinki Finland; Matti Harkonen, Helsinki Univ, Heisinki Finland Background: Endoscopy and biopsies are needed for diagnosis of atrophic gastritis in the antrum and corpus. Low serum levels of pepsinogen I (PGI) are used as a nonendoscopic test for atrophic corpus gastritis but nonendoscopic diagnosis of atrophic antrum gastritis has not been possible, so far. Objectives: The aim was to study whether the test panel composed of Elisa assays of serum PGI, gastrin-17 (G-17) after a prandial protein stimulus, and H.pylori antibodies (106) can be used as a tool for diagnosis of atrophic gastritis in the corpus and/or antrum. Methods: The study population consisted of 94 selectedpatients who underwent gastroscopy for dyspeptic symptoms in Jorvi Hospital. The results of the test panel were compared with the clinical and pathological diagnoses obtained from endoscopy and biopsies from the antrum and corpus (at least two from each compartment). PGI and 6-17 were determined by highly specific monoclonal antibodies based on immunoassaytest (Biohit PIc, Finland). Results:The new 6-17 test was highly specific and detectedonly amidated and glycine extendedG-17 without any cross,reactivity with other gasifies or relatedpopfides. As compared with histology, G-17 assay showed 92% and 88% sensitivity and specificity, respectively, in the diagnosis of advanced (moderate or severe) atrophic antrum gastritis. The correspondingvaluesfor PGI in atrophic corpus gastritis were 90% and 92%, respectively. The overall results obtained by the test panel and endoscopy agreed in 80% (75 of 94) of the cases. Of the 56 patients with endoscopic atrophic antrum or coq}us gastritis, 50 (89%) could be diagnosed with the present test panel. In the 38 cases without advancedatrophic antrum or corpus gastritis clinically, the test panel gave a positive result in three (8%) cases. Conclusions: The new blood test panel is a convenient and reliable tool in nonendoscopic diagnosis of gastritis and atrophic gastritis, and applicable for assessment of risk states of gastric cancer and peptic ulcer disease.

A-252

BACKGROUND:Oropharyngealdysphagia (OPD) is a very disabilitating problem for patients with neurologicaldisorders. Its therapy is mainly basedon rehabilitativemeasuresand, often, non-oral feeding (gastrostomy, N-G tube) is the only possible treatment. Cricomyotomy has been used in selectedcases wh'h conflicting results and, recently, injection of Botulinum toxin (BUT) into the cricopharyngealmuscle has beensuggested.In order to evaluatethe indication, efficacy and adverse effects of these procedures on patients with OPD of neurological origin we started this phase II study. METHODS:From June 1999 to date we enrolled 9 patients with severe OPD (9 m, 1 f, median age 65 years, r.: 21-79) of different origin (4 stroke, 1 trauma, 1 post CNS surgery, 1 diabetic neuropathy, 1 post vascular surgery, 1 idiopathic). The mediantime from the insult was 7 months. Sevenpatientswere fed through a gastrostomy and 4 had a tracheostomy. The patients underwent careful neurological, rehabilitative and ENT evaluation,videofluorographyand high fidelity manometfy. In all, rehabilitativetreatment proved to be uneftective,and therefore underwent percutaneousinjections of BuT A (10 units) into the cricopharyngealmuscle, previously identifiedwith EMG.Six patients had one session, 3 had 2 consecutivesessions. RESULTS:No complications were recorded.A good result was obtained in 3 cases (flu 18, 10 & 8 mos.). The other 6 patients underwent surgical cricomyotomy: only one responded to this treatment with satisfactory outcome (f/u: 12 rags.), whereas the other 5 did not improve, in spite of complimentary continuous rehabilitative treatment. Only 1 patient with a central damage respondedto therapy, whereas all the noncentral patients had a satisfactory outcome (p<.05). The duration of symptoms and the sever~ of videofluorographic alteration of swallowing did not differ between patients with good or poor result, even if an intact oral phase of swallowing was more frequent in patients with good outcome (p = .08). Finally, severe manometric alterations were associated to a poor outcome (p<.05). CONCLUSIONS:BuT injections of cdcopharyngealmuscle may play a role in the treatment of patients with OPD of neurological origin. However,the treatment seems to be more effective in patientswithout CNS damageand severefunction involvement. Patients who do not respond to BuT treatment are unlike to respond to surgical myotomy. 1311 Long-Term Treatment with Sulindac in Familial AdenomatousPolyposis:A Prospective Cohort Study. Marcia R. Cruz-Correa, Linda M. Hylind, Ketharine E. Romans, Susan V. Booker, Francis M. Giardiello, Johns Hopkins Univ, Baltimore, MD Background: Treatment of patients with familial adenomatous polyposis (FAP) can consist on colectomy with ileorectal anastomosis (IRA). Sulindac, a non-steroidal anti-inflammatory drug, inducesregressionof colorectaladenomasin the retainedrectal segmentof FAP patients, although long-term effects of this therapy are not fully understood. Therefore, we evaluated the long-term effectivenessand toxicity of sulindac in maintaining patients with retained rectal segments free of rectal adenomas. Methods: Twelve FAP patients (5 females; mean age 37.1 yrs, range 21.5-53.8 yrs) with IRA received sulindac (mean 158 mg/day, range 69-238 mg) for a mean period of 63.4 +_ 31.3 months (range 14-98 months). Number, size, and histologic grade of polyps, side effects, and compliance were assessed every 4 months. The sign test and Wiicoxon sign-rank test were used to estimate the difference in polyp number and