- Email: [email protected]
Cost-benefit analysis of Helicobacter pylori screening in dyspeptic subjects
April 1995
• EVIDENCE FOR PAF RECEPTOR ON RABBIT PARIETAL CELLS. I. Sobhani. Y. Cherifi, L. Moizo, JP. Laigneau, M. Mignon, MJM. Lewin, A. Bade. INSERM U10 - Bichat Hospital - 170 Btl. Ney 75877 Paris Cedex 18 - France. Background: We have previously reported secretion of PAF and precursors in the stomach in man (DigDisSci 1992; Gut 1993) and showed that PAF stimulates gastric acid secretion in vitro (Gastroenterology 1993): PAF-indnced acid secretion was inhibited by PAF antagonists and H+/K+ ATPase inhibitors while unaffected by H2 receptor antagonists. Furthermore, buffering of (Ca2+)i and (Ca2+)ext suppressed this effect. Thus, the aims of the present study Were to i) investigate the effect of PAF on (Ca2+)i in rabbit gastric glands; ii) detect PAF receptor mRNA. Materials and methods: Rabbit fundic glands were isolated and incubated by Fura-2AM 10 p2¢I for 30 min, and (Ca2+)i was measured using double wave-lenght spectrophotometer as previously described. RT-PCR experiments on total mRNA extracted from either isolated glands and purified isolated cell fractions (parietal, pepsin, and endocrine cells) using 2 primers selected in the cloned human leucocyte PAF receptor cDNA (Nature 92). Results : PAF increased (Ca2+)i in rabbit gastric glands in a concentration dependent manner with the maximum (340 + 45 nM vs 210 + 10 nM in resting glands) being reached for 0.1 ~tM. This response was inhibited by specific PAF antagonists. A single RTPCR product with the expected size (548 bp) was observed in total cell and in purified parietal cell fractions. No RT-PCR product was detectable in the pepsin and endocrine cell fractions. The sequencing of the single band showed more than 90% homology with human leucocyte PAF receptor. Conclusion : these data suggest that PAF stimulates gastric acid secretion via a specific receptor linked to intracellular calcium in rabbit gastric parietal cells.
• CURRENT PREVALENCE RATES AND RISK FACTORS OF PEPTIC ULCER IN THE UNITED STATES. Amnon Sonnenberg, James E. Evsrhart. The Medical College of Wisconsin, Milwaukee, Wl, and National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD. Objectives: To draw a current picture of the epidemiology and socio-demographic characteristics of peptic ulcer in the US. Methods: During the National Health Interview Survey (NHIS) of 1989, a special questionnaire on digestive disorders was administered to 42,000 randomly selected individuals. The occurrence of peptic ulcer was expressed as prevalence rates (and their 95% confidence intervals) per 100 living US residents. Odds ratios (OR) and their 95% confidence intervals were calculated by logistic regression. All statistics considered the sample weights and characteristics of the NHIS sampling design. Results: Of all US residents aged 18 and more, 10.28% (9.94-10.63%) had a past history of peptic ulcer. Of those, about one third, i.e. 3.35% (3.16-3.54%), had an ulcer during the last year. Gastric and duodenal ulcer each accounted for about one forth of all ulcers, i.e. 2.44% (2.26-2.63) and 2.53 (2.36-2.71%). The rest comprised peptic ulcers with site unspecified. Old age :(OR=1.19 per 10 years, 1.16-1.22), short education (2.00, 1.64-2.44), low family income (1.49, 1.31-1.69), being a veteran (1.22, 1.09-1.37), and smoking (1.40, 1.241.59) acted as significant and independent risk factors. Gastric and duodenal ulcer occurred in both sexes equally often. Conclusions: The varying declines of risk factors responsible for gastric and duodenal ulcer have resulted in a relatively uniform epidemiologic pattern of both ulcer types. The agerelated rise and socio-economic gradients of peptic ulcer could represent the historic scars of high infection rates with Helicobacter pylori experienced during early childhood.
Esophageal, Gastric, and Duodenal Disorders
A223
COST-BENEFIT ANALYSIS OF HELICOBACTER PYLORI SCREENING IN DYSPEPTIC SUBJECTS. Amnon Sonnenberg. VA Medical Center and the Medical College of Wisconsin, Milwaukee, WI 53295. BaCkground: The discovery of Helicobacter pylod (Hp) has opened the possibility to cure peptic ulcer (PUD) and prevent its occurrence. The present study analyzes the cost-benefit relationship of screening dyspeptic patients for Hp, in order to cure potential PUD and prevent future PUD attacks, as well as future gastric cancer. Methods: Screening for Hp in dyspeptic subjects is analyzed using a decision tree. In the decision tree, screening leads to a positive (30%) or negative (70%) test result. A positive result is followed by antibiotic therapy that may (60%) or may not (40%) successfully eradicate Hp. Successful eradication is associated with the potential benefits of healing dyspepsia (10%), preventing peptic ulcer (10%), or gastric cancer (0.12%). Testing for Hp and one coarse of antibiotic therapy, including one physician visit, are assumed to cost -$50 and -$200, respectively. Ulcer cure plus prevention, cancer prevention, or cure of dyspepsia are assumed to be associated with the benefits of saving future costs of +$7000, +$30000, or +$5000, respectively. In a sensitivity analysis, all mentioned rates and benefits are varied over a wide range, to test the robustness of the calculated decision outcomes. Results: Under baseline assumptions, the strategy of screening dyspeptic subjects for Hp and treating Hp-positive subjects is associated with a clear-cut benefit of +$112. In the sensitivity analysis, changes in the eradication rate of Hp or in the rate and benefit associated with gastric cancer prevention exert little influence. The cost-benefit relationship of Hp screening is influenced mostly by the monetary benefit of PUD prevention, the prevalence rate of PUD in Hp-positive patients, and the response rate of non-ulcer dyspepsia to Hp eradication. If the benefit of PUD prevention exceeds $4,000 and the PUD prevalence rate exceeds 10%, screening for lip in dyspeptic patients always pays off. A response of non-ulcer symptoms to Hp eradication in 5-10% of dyspeptic patients makes Hp screening a beneficial option, irrespective of PUD prevalence rate and the benefit of PUD prevention. Conclusions: In a previous analysis it was shown that, compared with all other treatment options, antibiotic therapy for eradication of Hp infection and cure of PUD is the cheapest treatment option, leading to expected costs of less than $1000 over a time period of 15 years. Since peptic ulcer has become so inexpensive, any benefit associated with its prevention has also decreased. Ironically, the effective means to deal with Hp infection may also abolish the need to screen for its occurrence.
B-CELL CLONAL EXPANSION IN GASTRIC BIOPSIFA5 OF PATIENTS WITH D Y S P E P S I A AND AUTOIMMUNE D I S E A S E S : E F F E C T OF H.PYLORI ERADICATION. D.Sorrentlilo, G.F.Ferraeeloli, S.DeVita, C.AveUlnl, C.A.Beltraml, A.Labombarda, V.Bernardis, F.DcBiase, R.Doleetti, M.Bolocchi, E.Bartoli. Depts of Internal Medicine and Pathology, School of Medicine, University of Udine and CRO, Aviano - Italy. We have previously s h o w n (Gast~'oenterology 106:A183) t h a t H.pylorl infection a n d gastric lymphoid follicles are frequently associated with B-cell clonal expansion. T h e s e f i n d i n g s support t h e t h e o r y t h a t H . p y l o r i p l a y s a role in t h e development of gastric M u c o s a Associated Lymphoid T i s s u e {MALT) l y m p h o m a . However, B-cell c l o n a l l t y m a y a l s o recognize o t h e r c a u s e s . To test t h i s h y p o t h e s i s we evaluated VDJ clonality by p o l y m e r a s e c h a i n r e a c t i o n a n d H.pylori Infection by histology in a n o r t h - i t a l i a n p a t i e n t population referred to u s for d y s p e p s i a (n=25) or for SJ~gren's s y n d r o m e (n=20}, a g r o u p k n o w n to develop v a r i o u s MALT l y m p h o m a s at a higher rote t h a n the general population. In addition, in two p a t i e n t s (one for e a c h group) clonallty w a s tested again after
successful
H,pylori
eradication
with
standard
antibiotic/antisecretive therapy. RESULTS: VDJ clonality w a s present in 9 / 2 5 patients with dyspepsia a n d in 9 / 2 0 p a t i e n t s with SJ6gren's s y n d r o m e . In t h e first g r o u p , clonality w a s associated in 78% of c a s e s with H.pylori infection a n d in 89% with gastric lymphoid follicles. C o r r e s p o n d i n g figures for the group w i t h s J s g r e n ' s s y n d r o m e w e r e 44% a n d 11% respectively. Finally, d e s p i t e H . p y l o r i e r a d i c a t i o n , V D J clonality persisted 6 weeks after the end of therapy. CONCLUSIONS: W h e n c o m p a r e d to p a t i e n t s w i t h dyspepsia, VDJ clonality in p a t i e n t s w i t h SjSgren s s y n d r o m e is l e s s often a s s o c i a t e d w i t h H.pylori infection. F u r t h e r m o r e , in b o t h g r o u p s , s u c c e s s f u l eradication of H.pylori m a y n o t r e s u l t in c e s s a t i o n o f t h e s t i m u l u s ( i ) l e a d i n g to B-cell c l o n a l ~¢pansion. A l t h o u g h firm c o n c l u s i o n s await a longer followu p a n d a larger n u m b e r of p a t i e n t s , o u r d a t a s u g g e s t t h a t factors o t h e r t h a n H.pylori, e s p e c i a l l y in p a t i e n t s w i t h autoimmune diseases, may trigger t h e c a s c a d e of e v e n t s leading to potential p r e - l y m p h o m a t o u s lesions.
• EVIDENCE FOR PAF RECEPTOR ON RABBIT PARIETAL CELLS. I. Sobhani. Y. Cherifi, L. Moizo, JP. Laigneau, M. Mignon, MJM. Lewin, A. Bade. INSERM U10 - Bichat Hospital - 170 Btl. Ney 75877 Paris Cedex 18 - France. Background: We have previously reported secretion of PAF and precursors in the stomach in man (DigDisSci 1992; Gut 1993) and showed that PAF stimulates gastric acid secretion in vitro (Gastroenterology 1993): PAF-indnced acid secretion was inhibited by PAF antagonists and H+/K+ ATPase inhibitors while unaffected by H2 receptor antagonists. Furthermore, buffering of (Ca2+)i and (Ca2+)ext suppressed this effect. Thus, the aims of the present study Were to i) investigate the effect of PAF on (Ca2+)i in rabbit gastric glands; ii) detect PAF receptor mRNA. Materials and methods: Rabbit fundic glands were isolated and incubated by Fura-2AM 10 p2¢I for 30 min, and (Ca2+)i was measured using double wave-lenght spectrophotometer as previously described. RT-PCR experiments on total mRNA extracted from either isolated glands and purified isolated cell fractions (parietal, pepsin, and endocrine cells) using 2 primers selected in the cloned human leucocyte PAF receptor cDNA (Nature 92). Results : PAF increased (Ca2+)i in rabbit gastric glands in a concentration dependent manner with the maximum (340 + 45 nM vs 210 + 10 nM in resting glands) being reached for 0.1 ~tM. This response was inhibited by specific PAF antagonists. A single RTPCR product with the expected size (548 bp) was observed in total cell and in purified parietal cell fractions. No RT-PCR product was detectable in the pepsin and endocrine cell fractions. The sequencing of the single band showed more than 90% homology with human leucocyte PAF receptor. Conclusion : these data suggest that PAF stimulates gastric acid secretion via a specific receptor linked to intracellular calcium in rabbit gastric parietal cells.
• CURRENT PREVALENCE RATES AND RISK FACTORS OF PEPTIC ULCER IN THE UNITED STATES. Amnon Sonnenberg, James E. Evsrhart. The Medical College of Wisconsin, Milwaukee, Wl, and National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD. Objectives: To draw a current picture of the epidemiology and socio-demographic characteristics of peptic ulcer in the US. Methods: During the National Health Interview Survey (NHIS) of 1989, a special questionnaire on digestive disorders was administered to 42,000 randomly selected individuals. The occurrence of peptic ulcer was expressed as prevalence rates (and their 95% confidence intervals) per 100 living US residents. Odds ratios (OR) and their 95% confidence intervals were calculated by logistic regression. All statistics considered the sample weights and characteristics of the NHIS sampling design. Results: Of all US residents aged 18 and more, 10.28% (9.94-10.63%) had a past history of peptic ulcer. Of those, about one third, i.e. 3.35% (3.16-3.54%), had an ulcer during the last year. Gastric and duodenal ulcer each accounted for about one forth of all ulcers, i.e. 2.44% (2.26-2.63) and 2.53 (2.36-2.71%). The rest comprised peptic ulcers with site unspecified. Old age :(OR=1.19 per 10 years, 1.16-1.22), short education (2.00, 1.64-2.44), low family income (1.49, 1.31-1.69), being a veteran (1.22, 1.09-1.37), and smoking (1.40, 1.241.59) acted as significant and independent risk factors. Gastric and duodenal ulcer occurred in both sexes equally often. Conclusions: The varying declines of risk factors responsible for gastric and duodenal ulcer have resulted in a relatively uniform epidemiologic pattern of both ulcer types. The agerelated rise and socio-economic gradients of peptic ulcer could represent the historic scars of high infection rates with Helicobacter pylori experienced during early childhood.
Esophageal, Gastric, and Duodenal Disorders
A223
COST-BENEFIT ANALYSIS OF HELICOBACTER PYLORI SCREENING IN DYSPEPTIC SUBJECTS. Amnon Sonnenberg. VA Medical Center and the Medical College of Wisconsin, Milwaukee, WI 53295. BaCkground: The discovery of Helicobacter pylod (Hp) has opened the possibility to cure peptic ulcer (PUD) and prevent its occurrence. The present study analyzes the cost-benefit relationship of screening dyspeptic patients for Hp, in order to cure potential PUD and prevent future PUD attacks, as well as future gastric cancer. Methods: Screening for Hp in dyspeptic subjects is analyzed using a decision tree. In the decision tree, screening leads to a positive (30%) or negative (70%) test result. A positive result is followed by antibiotic therapy that may (60%) or may not (40%) successfully eradicate Hp. Successful eradication is associated with the potential benefits of healing dyspepsia (10%), preventing peptic ulcer (10%), or gastric cancer (0.12%). Testing for Hp and one coarse of antibiotic therapy, including one physician visit, are assumed to cost -$50 and -$200, respectively. Ulcer cure plus prevention, cancer prevention, or cure of dyspepsia are assumed to be associated with the benefits of saving future costs of +$7000, +$30000, or +$5000, respectively. In a sensitivity analysis, all mentioned rates and benefits are varied over a wide range, to test the robustness of the calculated decision outcomes. Results: Under baseline assumptions, the strategy of screening dyspeptic subjects for Hp and treating Hp-positive subjects is associated with a clear-cut benefit of +$112. In the sensitivity analysis, changes in the eradication rate of Hp or in the rate and benefit associated with gastric cancer prevention exert little influence. The cost-benefit relationship of Hp screening is influenced mostly by the monetary benefit of PUD prevention, the prevalence rate of PUD in Hp-positive patients, and the response rate of non-ulcer dyspepsia to Hp eradication. If the benefit of PUD prevention exceeds $4,000 and the PUD prevalence rate exceeds 10%, screening for lip in dyspeptic patients always pays off. A response of non-ulcer symptoms to Hp eradication in 5-10% of dyspeptic patients makes Hp screening a beneficial option, irrespective of PUD prevalence rate and the benefit of PUD prevention. Conclusions: In a previous analysis it was shown that, compared with all other treatment options, antibiotic therapy for eradication of Hp infection and cure of PUD is the cheapest treatment option, leading to expected costs of less than $1000 over a time period of 15 years. Since peptic ulcer has become so inexpensive, any benefit associated with its prevention has also decreased. Ironically, the effective means to deal with Hp infection may also abolish the need to screen for its occurrence.
B-CELL CLONAL EXPANSION IN GASTRIC BIOPSIFA5 OF PATIENTS WITH D Y S P E P S I A AND AUTOIMMUNE D I S E A S E S : E F F E C T OF H.PYLORI ERADICATION. D.Sorrentlilo, G.F.Ferraeeloli, S.DeVita, C.AveUlnl, C.A.Beltraml, A.Labombarda, V.Bernardis, F.DcBiase, R.Doleetti, M.Bolocchi, E.Bartoli. Depts of Internal Medicine and Pathology, School of Medicine, University of Udine and CRO, Aviano - Italy. We have previously s h o w n (Gast~'oenterology 106:A183) t h a t H.pylorl infection a n d gastric lymphoid follicles are frequently associated with B-cell clonal expansion. T h e s e f i n d i n g s support t h e t h e o r y t h a t H . p y l o r i p l a y s a role in t h e development of gastric M u c o s a Associated Lymphoid T i s s u e {MALT) l y m p h o m a . However, B-cell c l o n a l l t y m a y a l s o recognize o t h e r c a u s e s . To test t h i s h y p o t h e s i s we evaluated VDJ clonality by p o l y m e r a s e c h a i n r e a c t i o n a n d H.pylori Infection by histology in a n o r t h - i t a l i a n p a t i e n t population referred to u s for d y s p e p s i a (n=25) or for SJ~gren's s y n d r o m e (n=20}, a g r o u p k n o w n to develop v a r i o u s MALT l y m p h o m a s at a higher rote t h a n the general population. In addition, in two p a t i e n t s (one for e a c h group) clonallty w a s tested again after
successful
H,pylori
eradication
with
standard
antibiotic/antisecretive therapy. RESULTS: VDJ clonality w a s present in 9 / 2 5 patients with dyspepsia a n d in 9 / 2 0 p a t i e n t s with SJ6gren's s y n d r o m e . In t h e first g r o u p , clonality w a s associated in 78% of c a s e s with H.pylori infection a n d in 89% with gastric lymphoid follicles. C o r r e s p o n d i n g figures for the group w i t h s J s g r e n ' s s y n d r o m e w e r e 44% a n d 11% respectively. Finally, d e s p i t e H . p y l o r i e r a d i c a t i o n , V D J clonality persisted 6 weeks after the end of therapy. CONCLUSIONS: W h e n c o m p a r e d to p a t i e n t s w i t h dyspepsia, VDJ clonality in p a t i e n t s w i t h SjSgren s s y n d r o m e is l e s s often a s s o c i a t e d w i t h H.pylori infection. F u r t h e r m o r e , in b o t h g r o u p s , s u c c e s s f u l eradication of H.pylori m a y n o t r e s u l t in c e s s a t i o n o f t h e s t i m u l u s ( i ) l e a d i n g to B-cell c l o n a l ~¢pansion. A l t h o u g h firm c o n c l u s i o n s await a longer followu p a n d a larger n u m b e r of p a t i e n t s , o u r d a t a s u g g e s t t h a t factors o t h e r t h a n H.pylori, e s p e c i a l l y in p a t i e n t s w i t h autoimmune diseases, may trigger t h e c a s c a d e of e v e n t s leading to potential p r e - l y m p h o m a t o u s lesions.