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Barrett's esophagus: Incidence of adenocarcinoma. An Italian multicentric perspective study
A152
AGA ABSTRACTS
• HELICOBACTER PYLORI DOES NOT INFLUENCE GASTRIC MUCOSAL ADAPTATION T O NSAIDS IN MAN. G~R. Lipseomb. N. Wallis, G. Armstrong, M.J. Goodman, W.D.W, Rees. Departments of Medicine and Histopathology, University of Manchester School of Medicine, Hope Hospital, Salford, and Bury General Hospital, U.K. Topical application of NSAIDs results in acute gastric mncosal injury and a fall in antral mucosal blood flow (MBF). This is followed by adaptation when gastric damage resolves and MBF returns to normal despite continued NSAID intake. The influence of H.pylori on these responses has not been investigated previously. Twelve healthy volunteers, H.pylori positive by.gastric biopsy, CLO test or C 13 urea breath test, were given a 28 day course of either dicofeaac 50rag b d or naproxea 500rag bd and gastroscoped before, 1, 7 and 28 days during treatment. Macroscopic gastric mucosal dmnage was assessed using a modified Lanza score (0--normal, 4=severe) and mucosal blood flow measured by laser doppler flowmetry in the corpus and antrum. Twelve age, sex and drug matched healthy H.pylori negative volunteers underwent the same protocol. Maximal gastric mucosal damage (median grade + IQR) occurred during the first 24 hours in both groups and was of the same magnitude (H. pylori +ve: 2.0, 1.03.0, H. pylori -ve: 2.0, 1.0-3.0). This damage was associated with a fall in antral MBF (mean + SEM ) from 53.0 + 4.1 to 44.5 + 315 arbitrary units in the H.Pylori +ve group (p=O.05) and from 57.2 + 3.2 to 36.8 + 4.6 arbitrary units in the H. pylori -ve group (p=0.005). There .was no significant difference in antral MBF changes between the 2 groups. Corpus MBF was not significantly affected by NSAID intake in either group. With continued NSAID administration gastric damage resolved in both groups and MBF returned to baseline (H.pylori +ve: 53.2 + 2.9, H pylori -ve 49.2 + 3.7 arbitrary units). These adaptive responses were not influenced by H.pylori. These observations suggest that H. pylori has no influence on either acute gastric mucosal damage or subsequent adaptation to NSAIDs.
• A SUSTAINED NET WATER FLUX IS MEASURABLE FOLLOWING DUODENAL ACID EXPOSWRE. EH L!vingstun, Division of General Surgery, VAMC West Los Angeles, and the UCLA School of Medicine, Los Angeles, Calif., 90024-6904 Our laboratory has demonstrated a dose bat not time dependent injury paRem following duodenal exposure to lumina! acid (Gastroenterology 103:481, 1992). Mathematical models of the mncobicarb0nate layer (A/P 247:G321, 1984) predict that for strong acid the major protective mechanism will be water flux through the mucus gel layer. The purpose of this study was to determine the rate and direction of
water flu( during acid perfusion. Methods: The duodenums of anesthetized rats (6-10 per group) were cananlated as previously described (Gastroenterology 103:481, 1992). They were perfused with saline for 30 minutes then with saline, .05, or .15 N HCI for 30 minutes then followed with another 30 minute saline perfusion. Every 5 minute the effluent was collected, weighed on a Mettler balance and titrated with .1 N HCI. In a separate group of experiments bicarbonate secretion was measured before and after the acid perfhsion. Results: Immediately following acid exposure there was a transient net fluid absorption. The absorption converted to net fluid secretion; transiently for .05 N HCI, but sustained for the duration ofthe acid and second saline perfusions for the .15 N HC1 group. The average net fluid secreti6n during the .15 N HCI perfusion was 5.0 _+ 1.1 ixl min-1 cm2 and remained at 5.4 _+ 0.8 ~tl min-1 cm2 afterwards (p<.05, compared to baseline, repeated measures ANOVA). There was no increase in bicarbonate secretion as compared to baseline in this group. Conclusion: 1) These results are' consistent with the mucobicarbonate mathematical model's prediction that net luminal flow is an essential component in protection against strong luminal acid. Based on our previous estimates of bicarbonate diffusion, we anticipated that this effect would be important for .15 but not .05 N HC1. The current study demonstrates sustained net fluid secretion only with the stronger acid, consistent with our model. 2)The resting absorption might carry acid to the duodenal lumen and upon injury be quickly converted to net secretion protecting against further injury. This phenomena explains the independence of duration of acid exposure in our previous studies.
GASTROENTEROLOGY, Vol. 108, No. 4
ONEPRAZOLERELATEDHYPERGASTRINEMIA: EFFECT OF LONG-TERM, DAILY VERSUSALTERNATEDAY THERAPY. M.Liqumsky, J Siguencia
and J.tysy, The GI Unit,Division of Medicine, Hadassah University Hospital & Medical School,Jerusalem g1120,Israel. Prolong treatment with omeprazolemay be associated with hypo-achlorhydria and hypergastrinemia leading to ECL cell hyperplasia and other effects such as bacreriat overgrowth or vitamin B,~ deficiency. In reflux esopnagitis long-term therapy is *indicated and hypergastrinemia may thus ensue more freguently. This study aimed to examine the effect of omeprazole (20mg) taken either daily or on alternate days on serum gastrin of patients treated for reflux esophagitis. Methods: Symptomatic patients with endoscopic features of moderate to s e v e r e reflux esophagitis were studied. Following i n i t i a l clinical improvement, omeprazole was continued for at least 3 months in 2 regimens: group I received 20mg daily and group II received 20mg every other day. Serum gastrin was measured after 12h of fasting by RIA k i t ICIS, France). A control group not receiving any acid blocking therapy was also studied for fasting serum )astrin. Results: No difference between the groups was noticed in maintaining clinical remission during the follow up period. Group I
Group I I
Controls
n
lg(F=I1;M=B)
IO(F=6;M=4)
8(F=4;M=4)
Age:range x±SE
26-80 61±3.5
55-80 69±2.5
30-74 51±3.4
Gastrin:range 41-450 (pg/ml) x±SE 155±26"
33-84 57±6.1
27-80 50±6.5
Treat.: range 3-36 (months) x±SE 11.8±2.2
4-12 7±1.0
.... (*p
In group I, I0 out of the 19 patients had high serum gastrin levels ranging from 140 to 450pg/ml, while none in group II ihad any increase in serum gastrin as compared to controls. iCenclusions: A significant increase in serum ~astrin levels !was observed only in patients on long-term dally omeprazole. Alternate-day omeprazole regimen may be beneficial in the ;maintenance therapy of reflux esophagitis, in reducing the potential side effects of prolonged hypergastrinemia, and also in reducing the cost of treatment.
BARRETT'S ESOPHAGUS: INCIDENCE OF ADENOCARCINOMA. AN ITALIAN MULTICENTRIC PERSPECTIVE STUDY. LuciD Lombardo,*Luigina Bonelli & G.O.S.P.E. (Gruppo Operative per Io Studio delle Precaocerosi Esofagee). Dept. Gastroenterology, Mauriziano Hospital, Torino &*I.S.T. Geneva; Italy. The present ad i n t e r i m data are part of an ongoing multicentric survey aimed at studying th e biologic characteristics and the natural history of Barrett's Esophagus (BE). From November 1987, 626 patients had multiple biopsies from the Iowe~ third of the esophagus because of moderate or severe GERD. Those aged up to 75, free from cancer at any site and from life-threatening diseases Were eligible for at least a yeg0cly endoscopic and histologic follow-up. Until November 1994, 259 of 586 eligible pts (44.2%) had one or more endoscopic and histologic examinations du~ing a period ranging from I month to 6.5 years (192 with histologic proven BE: 95 gastric type, 97 specialized noluranar epithelium (SEE) alone or mixed; 67 with esopha~itis). As a whole 192 pts with histologic diagnosis of BE at the basal examination had at least one endoscopie-histologic followup. Dysplasia w a s o b s e r v e d only in SCE.
INDEFINITE IO 22 Ii 5 3 LOW-GRADE 7 4 5 i HIGH-GRADE 2* I I* * In 2 patients Hi,h-grade dysplasia was associated to adenocarcinoma, overall patients with BE provided 458 py of followup and the incidence was 1/229 py. If the evalution was confined to patients with SeE, 234 py of follow-dp were provided and the incieende was i/I17 py.
AGA ABSTRACTS
• HELICOBACTER PYLORI DOES NOT INFLUENCE GASTRIC MUCOSAL ADAPTATION T O NSAIDS IN MAN. G~R. Lipseomb. N. Wallis, G. Armstrong, M.J. Goodman, W.D.W, Rees. Departments of Medicine and Histopathology, University of Manchester School of Medicine, Hope Hospital, Salford, and Bury General Hospital, U.K. Topical application of NSAIDs results in acute gastric mncosal injury and a fall in antral mucosal blood flow (MBF). This is followed by adaptation when gastric damage resolves and MBF returns to normal despite continued NSAID intake. The influence of H.pylori on these responses has not been investigated previously. Twelve healthy volunteers, H.pylori positive by.gastric biopsy, CLO test or C 13 urea breath test, were given a 28 day course of either dicofeaac 50rag b d or naproxea 500rag bd and gastroscoped before, 1, 7 and 28 days during treatment. Macroscopic gastric mucosal dmnage was assessed using a modified Lanza score (0--normal, 4=severe) and mucosal blood flow measured by laser doppler flowmetry in the corpus and antrum. Twelve age, sex and drug matched healthy H.pylori negative volunteers underwent the same protocol. Maximal gastric mucosal damage (median grade + IQR) occurred during the first 24 hours in both groups and was of the same magnitude (H. pylori +ve: 2.0, 1.03.0, H. pylori -ve: 2.0, 1.0-3.0). This damage was associated with a fall in antral MBF (mean + SEM ) from 53.0 + 4.1 to 44.5 + 315 arbitrary units in the H.Pylori +ve group (p=O.05) and from 57.2 + 3.2 to 36.8 + 4.6 arbitrary units in the H. pylori -ve group (p=0.005). There .was no significant difference in antral MBF changes between the 2 groups. Corpus MBF was not significantly affected by NSAID intake in either group. With continued NSAID administration gastric damage resolved in both groups and MBF returned to baseline (H.pylori +ve: 53.2 + 2.9, H pylori -ve 49.2 + 3.7 arbitrary units). These adaptive responses were not influenced by H.pylori. These observations suggest that H. pylori has no influence on either acute gastric mucosal damage or subsequent adaptation to NSAIDs.
• A SUSTAINED NET WATER FLUX IS MEASURABLE FOLLOWING DUODENAL ACID EXPOSWRE. EH L!vingstun, Division of General Surgery, VAMC West Los Angeles, and the UCLA School of Medicine, Los Angeles, Calif., 90024-6904 Our laboratory has demonstrated a dose bat not time dependent injury paRem following duodenal exposure to lumina! acid (Gastroenterology 103:481, 1992). Mathematical models of the mncobicarb0nate layer (A/P 247:G321, 1984) predict that for strong acid the major protective mechanism will be water flux through the mucus gel layer. The purpose of this study was to determine the rate and direction of
water flu( during acid perfusion. Methods: The duodenums of anesthetized rats (6-10 per group) were cananlated as previously described (Gastroenterology 103:481, 1992). They were perfused with saline for 30 minutes then with saline, .05, or .15 N HCI for 30 minutes then followed with another 30 minute saline perfusion. Every 5 minute the effluent was collected, weighed on a Mettler balance and titrated with .1 N HCI. In a separate group of experiments bicarbonate secretion was measured before and after the acid perfhsion. Results: Immediately following acid exposure there was a transient net fluid absorption. The absorption converted to net fluid secretion; transiently for .05 N HCI, but sustained for the duration ofthe acid and second saline perfusions for the .15 N HC1 group. The average net fluid secreti6n during the .15 N HCI perfusion was 5.0 _+ 1.1 ixl min-1 cm2 and remained at 5.4 _+ 0.8 ~tl min-1 cm2 afterwards (p<.05, compared to baseline, repeated measures ANOVA). There was no increase in bicarbonate secretion as compared to baseline in this group. Conclusion: 1) These results are' consistent with the mucobicarbonate mathematical model's prediction that net luminal flow is an essential component in protection against strong luminal acid. Based on our previous estimates of bicarbonate diffusion, we anticipated that this effect would be important for .15 but not .05 N HC1. The current study demonstrates sustained net fluid secretion only with the stronger acid, consistent with our model. 2)The resting absorption might carry acid to the duodenal lumen and upon injury be quickly converted to net secretion protecting against further injury. This phenomena explains the independence of duration of acid exposure in our previous studies.
GASTROENTEROLOGY, Vol. 108, No. 4
ONEPRAZOLERELATEDHYPERGASTRINEMIA: EFFECT OF LONG-TERM, DAILY VERSUSALTERNATEDAY THERAPY. M.Liqumsky, J Siguencia
and J.tysy, The GI Unit,Division of Medicine, Hadassah University Hospital & Medical School,Jerusalem g1120,Israel. Prolong treatment with omeprazolemay be associated with hypo-achlorhydria and hypergastrinemia leading to ECL cell hyperplasia and other effects such as bacreriat overgrowth or vitamin B,~ deficiency. In reflux esopnagitis long-term therapy is *indicated and hypergastrinemia may thus ensue more freguently. This study aimed to examine the effect of omeprazole (20mg) taken either daily or on alternate days on serum gastrin of patients treated for reflux esophagitis. Methods: Symptomatic patients with endoscopic features of moderate to s e v e r e reflux esophagitis were studied. Following i n i t i a l clinical improvement, omeprazole was continued for at least 3 months in 2 regimens: group I received 20mg daily and group II received 20mg every other day. Serum gastrin was measured after 12h of fasting by RIA k i t ICIS, France). A control group not receiving any acid blocking therapy was also studied for fasting serum )astrin. Results: No difference between the groups was noticed in maintaining clinical remission during the follow up period. Group I
Group I I
Controls
n
lg(F=I1;M=B)
IO(F=6;M=4)
8(F=4;M=4)
Age:range x±SE
26-80 61±3.5
55-80 69±2.5
30-74 51±3.4
Gastrin:range 41-450 (pg/ml) x±SE 155±26"
33-84 57±6.1
27-80 50±6.5
Treat.: range 3-36 (months) x±SE 11.8±2.2
4-12 7±1.0
.... (*p
In group I, I0 out of the 19 patients had high serum gastrin levels ranging from 140 to 450pg/ml, while none in group II ihad any increase in serum gastrin as compared to controls. iCenclusions: A significant increase in serum ~astrin levels !was observed only in patients on long-term dally omeprazole. Alternate-day omeprazole regimen may be beneficial in the ;maintenance therapy of reflux esophagitis, in reducing the potential side effects of prolonged hypergastrinemia, and also in reducing the cost of treatment.
BARRETT'S ESOPHAGUS: INCIDENCE OF ADENOCARCINOMA. AN ITALIAN MULTICENTRIC PERSPECTIVE STUDY. LuciD Lombardo,*Luigina Bonelli & G.O.S.P.E. (Gruppo Operative per Io Studio delle Precaocerosi Esofagee). Dept. Gastroenterology, Mauriziano Hospital, Torino &*I.S.T. Geneva; Italy. The present ad i n t e r i m data are part of an ongoing multicentric survey aimed at studying th e biologic characteristics and the natural history of Barrett's Esophagus (BE). From November 1987, 626 patients had multiple biopsies from the Iowe~ third of the esophagus because of moderate or severe GERD. Those aged up to 75, free from cancer at any site and from life-threatening diseases Were eligible for at least a yeg0cly endoscopic and histologic follow-up. Until November 1994, 259 of 586 eligible pts (44.2%) had one or more endoscopic and histologic examinations du~ing a period ranging from I month to 6.5 years (192 with histologic proven BE: 95 gastric type, 97 specialized noluranar epithelium (SEE) alone or mixed; 67 with esopha~itis). As a whole 192 pts with histologic diagnosis of BE at the basal examination had at least one endoscopie-histologic followup. Dysplasia w a s o b s e r v e d only in SCE.
INDEFINITE IO 22 Ii 5 3 LOW-GRADE 7 4 5 i HIGH-GRADE 2* I I* * In 2 patients Hi,h-grade dysplasia was associated to adenocarcinoma, overall patients with BE provided 458 py of followup and the incidence was 1/229 py. If the evalution was confined to patients with SeE, 234 py of follow-dp were provided and the incieende was i/I17 py.