does prior use of acid suppressive therapy predict etiology or affect outcome in acute upper gi...

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April 2000 5546 PRIMARY B-CELL GASTRIC LYMPHOMA OF MUCOSA-ASSO- CIATED LYMPHOID TISSUE WITHOUT HEUCOBACTER rr- LORI INFECTION. Taiji Akamatsu, Hideharu Miyabayashi, Kazuya Fujimori, Taimei Kaneko, Toru Fujisawa, Masahiro Matsuzawa, Kendo Kiyosawa, Tsutomu Kat- suyama, Shinshu Univ, Matsumoto, Japan. Primary gastric lymphoma of mucosa-associated lymphoid tissue (MALT) is known to be linked to infection with Helicobacter pylori (H. pylori) , and many cases of regression of gastric MALT lymphoma after eradication of H.pylori has been reported. We report 6 cases of gastric MALT lymphoma without H.pylori infection. The sex ratio was same (1:1). The patients' ages ranged from 59 to 77 years, the average being 68.8. Biopsy spepecimens revealed characteristic findings of MALT lymphoma including centrocyte- like cells within the lamina propria infiltrating the glandular epithlium to form Iymphoepitheliallesions in all ceses. Five of 6 cases were diagnosed low-grade MALT lymphoma, and remaining I case contained high-grade compornent. The absence of H.pylori was assessed by histological finding with immunostaining using anti-H.pylori antibody, culture, and rapid ure- ase test. One case was positive of hepatitis C antiboby, and another I case hapatitis B antigen. Five of 6 cases received antibacterial treatment consist of proton pump inhibitor, amoxicillin, and clarithromycin. Four of 5 cases showed no response, but remaining I case showed partial regression of lymphoma in the endoscopic and histological findings. H.pylori negative- gastric MALT lymphomas were few, and antibacterial treatment was usually ineffective. 5547 CHANGES IN ANGIOGENIC FACTORS DURING HEALING OF ACETIC-ACID-INDUCED GASTRIC ULCERS IN RATS AND THE EFFECT OF TREATMENT WITH A PROTON PUMP INHIBITOR. Masumi Akimoto, Hiroshi Hashimoto, Mutsuo Shigemoto, Katsuko Ya- mashita, Tokyo Women's Med Univ, Tokyo, Japan. In fetal angiogenesis,VEGF and its receptors are required from the early stage of lumen formation.These factors nonspecifically act on systemic blood vessels. During vascular maturation in the late stage of lumen formation, SDF-I and its receptor CXCR4 participate in an organ-specific manner in the formation of large blood vessels supplying the gastrointes- tinal tract. At the 100thAGA in 1999, we reported that KDR and FIt-I appear during early ulcer formation and that CXCR4 increases during healing and scar formation.This time we studied changes in SDF- I,CXCR4,and KDR during healing of acetic-acid -induced ulcers in rats and assessed the effects of treatment with a proton pump inhibitor (PPI). Subjects and methods:Male Wistar rats were used.Ulcers were induced by the application of 100% acetic acid as described by Okabe.The stomach was removed 3days(C3),7days(C7),12days(CI2),and 28days(C28) after ul- cer induction. The expressions of SDF-I,CXCR4,and KDR mRNA in frozen gastric tissue were measured by RT-PCR.The PPI group(P) was given rabeprazole in a subcutaneous dose of 30 mg/kg from the day after ulcer induction.The control group(CO) was not treated with acetic acid. Discussion: In the PPI-untreated group,all three factors peaked at C7. In the PPI groups,CXCR4 increased with time,and the value at PI2 was higher than that at CO(P <0.01 ).On day 12, thePPI-untreated group showed a trend toward decreased expression of three factors, whereas high values persisted in the PPI group. On day 28,both C28 and P28 showed a trend toward a decrease in all three factors,but the values remained higher in the PPI group. Our results suggest that these factors promote the maturation of blood vessels in the gastric wall and PPI may be involved in ulcer healing and the prevention of recurrence. Results' CO C3 C7 C12 C27 P3 P7 P12 P27 SDF-1 0.85 1.12 1.48 1.41 1.10 1.47 1.96 1.75 1.51 CXCR4 0.88 1.48 2.03 1.53 1.22 1.34 1.55 230 1.40 KDR 0.99 0.97 1.52 1.40 1.00 0.83 1.12 1.20 1.01 5548 IMMEDIATE ERADICATION OF HELICOBACTER PYLORI IN- FECTION SEEMS TO BE BENEFICIAL COMPARED TO SOLELY "PPI" TREATMENT IN THE MANAGEMENT OF BLEEDING DU- ODENAL ULCER. Istvan F. Altorjay, Zsuzsa S. Vitalis, Robert R. Szasz, Karoly K. Palatka, Miklos M. Udvardy, 2nd Dept Medicine, Debrecen, Hungary. Background: It is widely accepted that following the eradication of H.py- lori infection the recurrence of ulcer bleeding is rare. Hardly any reliable data however have been published about the effect of immediate eradica- tion therapy, in the management of bleeding duodenal ulcer. The aim of our study was to compare the effect of acute, one week eradication therapy AGAA1209 with one week oral PPI treatment, followed in both case by 4 weeks H2 blocker treatment in the management of H. pylori positive, bleeding duodenal ulcer (Forrest I.B, II.B). Patients and methods: 46 patients, who were accepted because of bleeding duodenal ulcer, or with signs of recent hemorrhage, - not taking NSAIDs, aspirin or coumarol - and proved to be H. pylori positive by rapid urease test and serology, were randomly divided into two groups: 24 patients received eradication therapy (2x30 mg lanso- prazole, 2xlOOO mg amoxicillin, 2x500 mg clarithromycin for one week) followed by 4 weeks famotidine treatment (40 mg/day), while 22 patients received solely oral PPI treatment (2x30 mg lansoprazole) for one week, followed also by famotidine (40 mg/day) for 4 weeks. Eradication was also carried out in the second group, just after the famotidine treatment. If necessary, endoscopic management of bleeding was performed at the beginning (heat probe unit or injection of diluted adrenaline), endoscopic revision was carried out after 72 hours and 5 weeks, UBT 8 weeks following the eradication. Several laboratory data were compared between the two groups. Results: One patient did not complete the trial in the first group and two in the other. Among those, who returned to control endos- copy, ulcer healing rate after 5 weeks was 100 % in both groups, H. pylori eradication was successful in 20123 vs. 17120 cases, no severe rebleeding occured and there was no need of surgical intervention. No significant difference in the need of transfusion and decrease of haemoglobine level could be found between the two groups. However, although no laxative treatment was given, blood urea level returned to normal within 3,2 days vs. 3,8 days and fecal occult blood test became negative within 4,4 days vs, 5,3 days in the two groups. Conclusion: Although the number of patients has still to be increased to obtain more convincing results, according to our preliminary observation, immediate eradication therapy seems to be ben- eficial by accelerating the healing process in the management of H. pylori positive bleeding duodenal ulcer. 5549 DOES PRIOR USE OF ACID SUPPRESSIVE THERAPY PREDICT ETIOLOGY OR AFFECT OUTCOME IN ACUTE UPPER GI BLEEDING? Rafael Amaro, Manuel F. Bustamante, Jorge Lascano, Neil H. Stollman, Univ of Miami, Miami, FL. Background: With the increasing use of proton-pump inhibitors (PPls) and H-2 blockers, many patients are being maintained on acid-suppressive therapy (AST). The aim of this study was to determine if pre-hospital use of AST would alter etiology andlor outcome in patients presenting with acute upper GI bleeding (UGIB). Methods: We retrospectively reviewed all patients presenting to the ER with acute UGIB from l/99-6/99. Patients with GI malignancies were excluded. History, endoscopic findings and hospital course were recorded. Patients were divided into two groups based on their use (Group I) or non-use (Group 2) of AST prior to admission. Results: 100 patients (76 male, 24 female) were included. Mean age was 54 years (range: 24-87). 29 patients were taking AST (12 PPls, 17 H2- blockers). Both groups were similar for age/sex. The etiology of the UGIB was similar in Group I vs Group 2: PUD (48% vs 46%), varices (21% vs 18%), others (31% vs 35%). There were significantly more patients taking NSAIDs in Group 2 than in Group I (39% vs 10%, p<0.005), and significantly more patients with a past history of PUD in Group I than in Group 2 (55% vs II %, p<O.OOI). Both findings remained significant when analyzing patients with PUD as the cause of their UGIB. Clinical outcomes were similar in Groups I and 2 (table). Conclusion: The prior use of acid-suppressive medications does not influence the etiology or effect the outcome of patients presenting with acute UGIB. There is a trend for a shorter total hospital and ICU LOS in patients taking AST, but this did not attain statistical significance. Other factors, such as the use of NSAIDs or prior history of PUD may be more important in influencing the outcome of patients with acute UGIB. OUTCOME AcidSuppression (Group 1) NoacidsuppresSion (Group 2) Transfused 13/29 (45%) 25/71 (35%) NS Repeat EGO 5/29 (17%) 12/71 (17%) NS Hospital LOS 5.2days 6.7days NS ICU admit 9/29 (31%) 24/71 (34%) NS ICU LOS 3.3days 5.5days NS Surgery 0 2/71 (3%) NS Mortality 1/29 (3.4%) 3/71 (4.2%) NS

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Page 1: Does prior use of acid suppressive therapy predict etiology or affect outcome in acute upper GI bleeding?

April 2000

5546

PRIMARY B-CELL GASTRIC LYMPHOMA OF MUCOSA-ASSO­CIATED LYMPHOID TISSUE WITHOUT HEUCOBACTER rr­LORI INFECTION.Taiji Akamatsu, Hideharu Miyabayashi, Kazuya Fujimori, Taimei Kaneko,Toru Fujisawa, Masahiro Matsuzawa, Kendo Kiyosawa, Tsutomu Kat­suyama, Shinshu Univ, Matsumoto, Japan.

Primary gastric lymphoma of mucosa-associated lymphoid tissue (MALT)is known to be linked to infection with Helicobacter pylori (H. pylori) , andmany cases of regression of gastric MALT lymphoma after eradication ofH.pylori has been reported. We report 6 cases of gastric MALT lymphomawithout H.pylori infection. The sex ratio was same (1:1). The patients' agesranged from 59 to 77 years, the average being 68.8. Biopsy spepecimensrevealed characteristic findings of MALT lymphoma including centrocyte­like cells within the lamina propria infiltrating the glandular epithlium toform Iymphoepitheliallesions in all ceses. Five of 6 cases were diagnosedlow-grade MALT lymphoma, and remaining I case contained high-gradecompornent. The absence of H.pylori was assessed by histological findingwith immunostaining using anti-H.pylori antibody, culture, and rapid ure­ase test. One case was positive of hepatitis C antiboby, and another I casehapatitis B antigen. Five of 6 cases received antibacterial treatment consistof proton pump inhibitor, amoxicillin, and clarithromycin. Four of 5 casesshowed no response, but remaining I case showed partial regression oflymphoma in the endoscopic and histological findings. H.pylori negative­gastric MALT lymphomas were few, and antibacterial treatment wasusually ineffective.

5547

CHANGES IN ANGIOGENIC FACTORS DURING HEALING OFACETIC-ACID-INDUCED GASTRIC ULCERS IN RATS AND THEEFFECT OF TREATMENT WITH A PROTON PUMP INHIBITOR.Masumi Akimoto, Hiroshi Hashimoto, Mutsuo Shigemoto, Katsuko Ya­mashita, Tokyo Women's Med Univ, Tokyo, Japan.

In fetal angiogenesis,VEGF and its receptors are required from the earlystage of lumen formation.These factors nonspecifically act on systemicblood vessels. During vascular maturation in the late stage of lumenformation, SDF-I and its receptor CXCR4 participate in an organ-specificmanner in the formation of large blood vessels supplying the gastrointes­tinal tract. At the 100thAGA in 1999, we reported that KDR and FIt-Iappear during early ulcer formation and that CXCR4 increases duringhealing and scar formation.This time we studied changes in SDF­I,CXCR4,and KDR during healing of acetic-acid -induced ulcers in ratsand assessed the effects of treatment with a proton pump inhibitor (PPI).Subjects and methods:Male Wistar rats were used.Ulcers were induced bythe application of 100% acetic acid as described by Okabe.The stomachwas removed 3days(C3),7days(C7),12days(CI2),and 28days(C28) after ul­cer induction. The expressions of SDF-I,CXCR4,and KDR mRNA infrozen gastric tissue were measured by RT-PCR.The PPI group(P) wasgiven rabeprazole in a subcutaneous dose of 30 mg/kg from the day afterulcer induction.The control group(CO) was not treated with acetic acid.Discussion: In the PPI-untreated group,all three factors peaked at C7. In thePPI groups,CXCR4 increased with time,and the value at PI2 was higherthan that at CO(P <0.01 ).On day 12, thePPI-untreated group showed atrend toward decreased expression of three factors, whereas high valuespersisted in the PPI group. On day 28,both C28 and P28 showed a trendtoward a decrease in all three factors,but the values remained higher in thePPI group. Our results suggest that these factors promote the maturation ofblood vessels in the gastric wall and PPI may be involved in ulcer healingand the prevention of recurrence.

Results'CO C3 C7 C12 C27 P3 P7 P12 P27

SDF-1 0.85 1.12 1.48 1.41 1.10 1.47 1.96 1.75 1.51CXCR4 0.88 1.48 2.03 1.53 1.22 1.34 1.55 230 1.40KDR 0.99 0.97 1.52 1.40 1.00 0.83 1.12 1.20 1.01

5548

IMMEDIATE ERADICATION OF HELICOBACTER PYLORI IN­FECTION SEEMS TO BE BENEFICIAL COMPARED TO SOLELY"PPI" TREATMENT IN THE MANAGEMENT OF BLEEDING DU­ODENAL ULCER.Istvan F. Altorjay, Zsuzsa S. Vitalis, Robert R. Szasz, Karoly K. Palatka,Miklos M. Udvardy, 2nd Dept Medicine, Debrecen, Hungary.

Background: It is widely accepted that following the eradication of H.py­lori infection the recurrence of ulcer bleeding is rare. Hardly any reliabledata however have been published about the effect of immediate eradica­tion therapy, in the management of bleeding duodenal ulcer. The aim of ourstudy was to compare the effect of acute, one week eradication therapy

AGAA1209

with one week oral PPI treatment, followed in both case by 4 weeks H2blocker treatment in the management of H. pylori positive, bleedingduodenal ulcer (Forrest I.B, II.B). Patients and methods: 46 patients, whowere accepted because of bleeding duodenal ulcer, or with signs of recenthemorrhage, - not taking NSAIDs, aspirin or coumarol - and proved to beH. pylori positive by rapid urease test and serology, were randomly dividedinto two groups: 24 patients received eradication therapy (2x30 mg lanso­prazole, 2xlOOO mg amoxicillin, 2x500 mg clarithromycin for one week)followed by 4 weeks famotidine treatment (40 mg/day), while 22 patientsreceived solely oral PPI treatment (2x30 mg lansoprazole) for one week,followed also by famotidine (40 mg/day) for 4 weeks. Eradication was alsocarried out in the second group, just after the famotidine treatment. Ifnecessary, endoscopic management of bleeding was performed at thebeginning (heat probe unit or injection of diluted adrenaline), endoscopicrevision was carried out after 72 hours and 5 weeks, UBT 8 weeksfollowing the eradication. Several laboratory data were compared betweenthe two groups. Results: One patient did not complete the trial in the firstgroup and two in the other. Among those, who returned to control endos­copy, ulcer healing rate after 5 weeks was 100 % in both groups, H. pylorieradication was successful in 20123 vs. 17120 cases, no severe rebleedingoccured and there was no need of surgical intervention. No significantdifference in the need of transfusion and decrease of haemoglobine levelcould be found between the two groups. However, although no laxativetreatment was given, blood urea level returned to normal within 3,2 daysvs. 3,8 days and fecal occult blood test became negative within 4,4 days vs,5,3 days in the two groups. Conclusion: Although the number of patientshas still to be increased to obtain more convincing results, according to ourpreliminary observation, immediate eradication therapy seems to be ben­eficial by accelerating the healing process in the management of H. pyloripositive bleeding duodenal ulcer.

5549

DOES PRIOR USE OF ACID SUPPRESSIVE THERAPY PREDICTETIOLOGY OR AFFECT OUTCOME IN ACUTE UPPER GIBLEEDING?Rafael Amaro, Manuel F. Bustamante, Jorge Lascano, Neil H. Stollman,Univ of Miami, Miami, FL.

Background: With the increasing use of proton-pump inhibitors (PPls) andH-2 blockers, many patients are being maintained on acid-suppressivetherapy (AST). The aim of this study was to determine if pre-hospital useof AST would alter etiology andlor outcome in patients presenting withacute upper GI bleeding (UGIB). Methods: We retrospectively reviewed allpatients presenting to the ER with acute UGIB from l/99-6/99. Patientswith GI malignancies were excluded. History, endoscopic findings andhospital course were recorded. Patients were divided into two groups basedon their use (Group I) or non-use (Group 2) of AST prior to admission.Results: 100 patients (76 male, 24 female) were included. Mean age was 54years (range: 24-87). 29 patients were taking AST (12 PPls, 17 H2­blockers). Both groups were similar for age/sex. The etiology of the UGIBwas similar in Group I vs Group 2: PUD (48% vs 46%), varices (21% vs18%), others (31% vs 35%). There were significantly more patients takingNSAIDs in Group 2 than in Group I (39% vs 10%, p<0.005), andsignificantly more patients with a past history of PUD in Group I than inGroup 2 (55% vs II %, p<O.OOI).Both findings remained significant whenanalyzing patients with PUD as the cause of their UGIB. Clinical outcomeswere similar in Groups I and 2 (table). Conclusion: The prior use ofacid-suppressive medications does not influence the etiology or effect theoutcome of patients presenting with acute UGIB. There is a trend for ashorter total hospital and ICU LOS in patients taking AST, but this did notattain statistical significance. Other factors, such as the use of NSAIDs orprior history of PUD may be more important in influencing the outcome ofpatients with acute UGIB.

OUTCOME AcidSuppression (Group 1) NoacidsuppresSion (Group 2)

Transfused 13/29 (45%) 25/71 (35%) NSRepeat EGO 5/29 (17%) 12/71 (17%) NSHospital LOS 5.2days 6.7days NSICU admit 9/29 (31%) 24/71 (34%) NSICU LOS 3.3days 5.5days NSSurgery 0 2/71 (3%) NSMortality 1/29 (3.4%) 3/71 (4.2%) NS