Scandinavian Journal of Gastroenterology
ISSN: 0036-5521 (Print) 1502-7708 (Online) Journal homepage: http://www.tandfonline.com/loi/igas20
Helicobacter pylori and Chronic Gastritis: An Increased Risk of Peptic Ulcer? A Review P. Sipponen To cite this article: P. Sipponen (1991) Helicobacter pylori and Chronic Gastritis: An Increased Risk of Peptic Ulcer? A Review, Scandinavian Journal of Gastroenterology, 26:sup186, 06-10, DOI: 10.3109/00365529109103980 To link to this article: http://dx.doi.org/10.3109/00365529109103980
Published online: 08 Jul 2009.
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Date: 30 March 2016, At: 04:46
Helicobacter pylori and Chronic Gastritis: an Increased Risk of Peptic Ulcer? A Review P. SIPPONEN Dcpt. of Pathology, Jorvi Hospital, Espoo Finland
Sipponen P. Hdicohucter pylori and chronic gastritis: an increased risk of peptic ulcer? A review. Scand J Gastroenterol 1991, 26(suppl), 6-10
Downloaded by [University of Saskatchewan Library] at 04:46 30 March 2016
Key
MW~S:
Peptic ulcer; gastritis; Neli(nhucter pylori
Pentti Sipponcn. M.D.,Depr. of'Puthology, Jorvi Hospitul. SF-02740 E S ~ O OFinland , Fux: +3.78-0-86/2800
Probably more than 80%~of cases of chronic gastritis are associated with coexisting Helicohucter pylori (HP) infection (1 -3), and both the HP and the gastritis are strongly linked with peptic ulcer (4-lo), supporting the view that they have a relationship to the development of the ulcer disease (1 1-15). From the viewpoint of the pathogenesis of peptic ulcer, several statements and arguments can be presented concerning the participation of HP infection and gastritis in the sequence of events which at the worst culminate in ulcer.
H. pylori is the major muse of' chronic. gastritis Koch's postulates concerning the causal relationship between HP and gastritis seem to be satisfactorily fulfilled (16,17). In pracljce, the bacterium or antibodies against it are found in every case of chronic gastritis, at least in the early stages of the process. The bacterium can be isolated and grown in pure cultures from affected subjects, and the disease can be reproduced when the bacterium is inoculated into susceptible animals or volunteers. In addition, colloidal bismuth, together with various antimicrobial drugs, leads to the eradication of the bacterium in most of the infected patients (15), and the treatment leads to a reduction in the grade and extent of gastritis (3,lX). The acute inflammation ("activity" of the gastritis) disappears quickly after the eradication. The chronic inflammation diminishes in grade more slowly but will finally result in complete disappear-
ance of the gastritis.
Gastritis leads to utrophy of' the underlying mucosa The HP-induced gastritis results in a slow and gradual development of atrophy and metaplasia in the underlying mucosa in a great number of affected subjects (19-26). In the general population the appearance of cases with atrophy and intestinal tnetaplasia follows the appearance of cases with inflammation alone. On an average, the prevalence of cases with atrophy and metaplasia increases steadily with increasing age of the cohort. Correspondingly there occurs an increase in the extent of the atrophy and metaplasia in affected subjects with age. In the elderly, atrophy with accompanying metaplastic changes is a common finding and is found in a high proportion of subjects in the general population. The progression of gastritis to atrophic stages is probably not a uniform process (25),and may dissimilarly affect antrum and corpus in different individuals. Gastritis is slow in progression, may last for years or decades, and rarely heals spontaneously. In the course of time, some percentage of the HP-infected people will develop end-stages of the atrophic process, i.e., chronic gastritis with severe atrophy in the corpus or antral mucosa, or in both simultaneously. Atrophy implies a loss of normal glands, and consequently results in impairment of the gas-
Downloaded by [University of Saskatchewan Library] at 04:46 30 March 2016
H P , Gostritis and Peptic Ulcer
tric functions; for instance, in atrophy of the corpus mucosa it results in a low acid output, and in atrophy of the antral mucosa in a low rclease of gastrin from antral G cells (27,28). Evidence exists that the HP infection and the associated gastritis reduce resistance of the gastric mucosa, a phenomenon which may contribute to development of peptic ulcer and of other gastric diseases (see 5 ) . The HP-related enzymatic and toxic reactions, and a triggering of manifold immunological reactions in the gastric mucosa, as well as the local production of ammonia from endogenous urea by the bacterium, are some of the factors that may severely distort the mucosal integrity. The significance and details of these mechanisms are, however, still largely unknown. In regard to the risk of peptic ulcer, gastritis seems to exert a dual influence (29). In the genesis of peptic ulcer, gastritis may affect both the protective and the aggressive mechanisms, these influences being dependent upon the topography and grade of gastritis and atrophy in the stomach. The inflammation and the HP infection themselves may increase the risk of ulcer, whereas a marked atrophy in the corpus mucosa may decrease this risk by lowering the aggressive capacity of the acid-peptic factor.
a genetic property) the risk of peptic ulcer in antral gastritis may be even 50-fold that in subjects without these risk factors (30). Gastritis precedes peptic ulcer Available evidence indicates that chronic gastritis precedes the formation of peptic ulcer (42), suggesting that the gastritis is a real risk factor for peptic ulcer instead of being a simple result of the ulcer itself, This hypothesis of an HP-gastritis-ulcer sequence is supported by the long-term follow-up studies of patients with and without gastritis (42). These prospective studies demonstrate a remarkable cumulative rate of peptic ulcer in subjects with gastritis compared to subjects with normal stomach (both antral and corpus mucosa are normal) (Table I). In middle-aged males the 10-year cumulative risk of symptomatic peptic ulcer, of DU in particular, may exceed 20% in the antral gastritis (inflammation in antral mucosa only) or in the pangastritis (inflammation in both antral and corpus mucosa), whereas it is nearly zero in males with a normal stomach. Table I. Mean cumulative rate of DU or GU in a 10-year follow-up of male subjects with or without gastritis (source from ref. 42) Rate of DU or GU Histology
Risk of peptic ulcer is increased in gastritis Although gastritis is a common lesion in the general population, it is many times more prevalent in patients with peptic ulcer, and is associated almost invariably with both DU and GU if NSAID-induced ulcer cases are excluded (29-43). Studies carried out in Finland, Estonia and Poland (29,30) suggest that the risk Of peptic ulcer is high in the presence of chronic antral gastritis. The relative risk (RR) of DU or GU is On the average l o times higher in subjects with antral gastritis than in subjects with norsex In connection with the (gender is an independent risk factor for peptic ulcer) and non-secretor status (another independent risk factor; the subject does not secrete blood group substances in the gastric mucus -
7
Total
No.
("/u)
60
0
(0%)
Chronic antral gastritis
106
16
(15%)
Chronic corpus gastritis, or pangastritis with atropy of corpus mucosa
12
1
(8%)
Normal antrum and corpus
In contrast to the increased risk of peptic ulcer in antral gastritis or pangastritis, the risk of ulcer is low in the chronic corpus gastritisor in the pangastritis in which moderate or Severe atrophy of the corpus mucOSa coexists with the inflammation. This conclusion is by both cross-sectional and follow-up studies (29, 32,33,43). Furthermore, the inverse relationship between the ulcer risk and the grade of atrophy of the body gastritis appears logical when con-
8
P . Sipporieri
Table 11. Guidelines for interpretation of the risk of peptic ulcer in gastritis of different topographies and grades Histology
Interpretation
Nomial aiitrum and corpus
Risk of peptic ulcer is low and ulcer disease is improbable. Outputs of acid and pepsin are normal or high. HP is absent.
Chronic antnit gastritis
Cumulative risk of peptic ulcer is considerable, in middle-aged malcs in particular. Normal or high acid and pepsin outputs. HI' is practically always present and [he grade of HP colonisation is often high.
Chronic corpus gastritis or pangastritis with atrophy of corpus mucosa
Peptic ulcer disease improbable. Acid and pepsin outputs are low. HP is common but the grade 0 1 colonisation is usually low. Risk of pernicious anaemia if the atrophy is severe.
Downloaded by [University of Saskatchewan Library] at 04:46 30 March 2016
HP = Ildicobacrw p y h i
sidering the impairment in acid output in corpus atrophy, and this fits well with the functional consequences in the atrophy. Thus the atrophy is followed by low outputs of acid and pepsin, which correspondingly results in a decreased risk of peptic ulcer, irrespective of the presence and grade of the inflammation and HP infection in the antral mucosa. Gastric ulcer may occur, however, in subjects with marked atrophic changes and may be occasionally observed even in subjects with advanced corpus atrophy (32-34). A rapid development and progrcssion of corpus atrophy seems to occur in at least some of the patients with angular or high GU, in contrast to DU patients in whom corpus atrophy is rarely seen (44). In addition, the development of corpus atrophy in thc GU patients scems to modify the course of the disease. The long-term follow-up studies of Maaroos et al. (32) in Estonia have shown that the progression of corpus gastritis to advanced atrophic stages reduces the likelihood of active ulcer. It has been estimated (32) that the "life-span'' of the GU disease could be 10-15 years in these patients, during which time the acid-peptic factor will be reduced so that it no longer is able to overcome the protective mechanisms of the mucosa.
agement of peptic ulcer, bismuth and antibiotics provide new possibilities to handle HP infection, the strategy being the eradication of the HP infection with the aim to break the HPgastritis-ulcer scquence. Several trials (4548) have indeed shown that, in contrary to the traditional therapy, the eradication of the bacterium results in a long remission of the disease and in long-lasting prevention of ulcer recurrences. From the viewpoint of the HP-gastritis-ulcer sequence, peptic ulcer can be seen as a late complication of a H . pylori infection. There is evidence to suggest that in the multifactorial background of peptic ulcer disease, the HP infection and gastritis are indeed important and significant risk factors for the development of ulcer. In addition, in practical work the presence, type and grade of gastritis can be used in the interpretation of the risk of ulcer provided adequate specimens for microscopy are available from the antrum and corpus inucosa (Table 11).
I.
Marshall BJ, Warren JR. Unidcntified curved bacilli on gastric epithelium in the stomach of patients with gastritis and peptic ulceration. Lancet 1984, I , 121 I -
Erwdicution of H. pylori uflect.7 the cause of peptic ulcer- disease In the multifactorial pathogenesis of peptic ulcer. HP infection and gastritis are factors worth consideration in attempts to control the ulcer disease (see 5,15). In the practical man-
2.
Marshall BJ, McCechie DB, Rogei-s PA, Clancy RJ. Pyloric Cumpylohmter. infection and gastroduodenal disease. Med J Austr 1985, 142, 439-443 Rauws EAJ, Langenberg W, Houthdf HJ- Zanen HC, Tytgat GNJ. Cmnpylobocfer pylori-associated chronic active gastritis. A prospective study of its prevalence and the effects of antibacterial and antiulcer treatment.
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gression of gastritis at a population level. Scand J Gastroenterol 1976, 1 I. 597-601 Siurala M, Sipponen P, Kekki M. Chronic gastritis: dynamic and clinical aspects. Scand J Gastroenterol 1985, 20(suppl loo), 69-79 Siurala M, Sipponen P, Kekki M. Cumpylohuc,ter pylori in a sample of Finnish population: rclations to morphology and function of gastric niucosa. Gut 1988, 29, 909-915 Stadelmann 0, Elster K, Stolte M, f r uf.The peptic gastric ulcer - histotopographic and functional investigations. Scand J Gastroenterol 1971, 6, 613-623 Coma P. The epidemiology and pathogenesis of chronic gastritis. Front Gastrointest Res 1980, 6, 98108
2 5 . Kekki M, Siurala M, Varis K, Sipponcn P, Sistonen P.
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Nevanlinna HR. Classification principles and genetics of chronic gastritis. Scand J Gastroenterol 1987. 22(suppl 141) Kreuning J, Bosman FT, Kuiper G, Wal AM, Lindeman J. Gastric and duodenal mucosa in "healthy" individuals. An endoscopic and histological study of SO volunteers. J Clin Pathol 1978, 31. 69-77 Ihamiiki T, Varis K, Siurala M. Morphological, functional and immunological state of the gastric mucosa in gastric carcinoma families. Comparison with a computer-matched family sample. Scand J Gastrocnterol 1979, 14, 80 1 -8 I2 Siurala M, Varis K, Kckki M. New aspects on epidemiology. genetics, and dynamics of chronic gastritis. Front Gastrointest Res 1980, 6, 148-166 Sipponen P, Seppala K, Aarynen M, Kettunen P. Chronic gastritis and gastroduodenal ulcer: a casecontrol study on risk of coexisting duodenal or gastric ulcer in patients with gastritis. Gut 1989. 30, 922-929 Sipponen P, Aarynen M. Kiiirilinen 1, Kettunen P. Helske T, Sepplli K. Chronic antral gastritis, Lewisa + phenotype and male sex in predicting coexisting duodenal ulcer. Scand J Gastroenterol 1989, 24, 581-
588 31. Jnnxson K-A, Striim M, Bodemar G, Norrby K. His-
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tologic changes in the gastroduodenal mucosa after long-term medical treatment with cimetidine or parietal cell vagotomy in patients with juxtapyloric ulcer diseasc. Scand J Gastroenterol 1988, 23. 433-441 Maaroos H-I, Salupere V, Uibo R, Kekki M, Sipponcn P. Seven-year follow-up of chronic gastritis in gastric ulcer patients. Scand J Gastroenterol 1985, 20, 198204 Laszcwics W, Gabryelewicz A, Sipponen P. Kckki M, Laxin F, Siurala M. Gastric ulcer and gastritis: resulls of short-term follow-up examinations. Hepato-Gastroenterology 1987, 34, 265-268 Schrager J, Spink R, Mitra S. The antrum in patients with duodenal and gastric ulcers. Gut 1967, 8, 497508 Meister H, Holubarch CH, Haferkamp 0, Schlag 0,
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Herfarth CH. Gastritis, intestinal metaplasia, and dysplasia \'ersus benign ulcer in stomach and duodenum and gastric carcinoma. A histotopographic study. Pathol Res Prdct 1979, 164. 259-269 Overgaard Nielsen H, Munoz JD, Kronborg 0, Andersen D. The antrum in duodenal ulcer patients. Scand J Gastroenterol 1981, 16, 491-493 Earlam RJ, Amerigo J, Kakavoulis T, Pollock DJ. Histological appearances of oesophagus, antrum and duodenum and their correlation with symptoms in patients with duodenal ulcer. Gut 1985, 26, 95-100 Meikle DD, Taylor KB, Truelove SC, Whitehead R. Gastriris, duodenitis, and circulating levels of gastrin in duodenal ulcer before and after vagotomy. Gut 1976, 17. 719-728 Cheli R, Giacosa A. Duodenal ulcer and chronic gastritis. Endoscopy 1986, 18. 125-126 llui W-M, Lam A-K, Ho J, ef al. Chronic antral gastritis in duodenal ulcer. Natural history and treatment with prostaglandin E l . Gastroenterology 1986, 91,
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41. Mackay IR. Hislop IG. Chronic gastritis and gastric ulcer. Gut 1966, 7, 227-233 42. Sipponen P, Varis K, Fraki 0, Korri U-M. Sepplla K , Siurala M. Cumulative 10-year risk of symptomatic duodenal and gastric ulcer in patients with or without
4X.
chronic gastritis. A clinical follow-up of 454 patients. Scand J Gastroenterol 1990, 25, 966-973 Kekki M. Sipponen P, Siurala M, Lasxewicz W. Peptic ulcer and chronic gastritis: their relation to age and sex, and to location of ulcer and gastritis. Gastroenterol Clin Biol 1990, 14, 217-223 Kekki M, Sipponen P, Siurala M. Progression of antral and body gastritis in patients with active and healed duodenal ulcer and duodenitis. Scand J Gastroenterol 1984, 19, 382-388 Marshall BJ, Goodwin CS, Warren JR, Murray R, Blincow ED, Blackbourn SJ, Phillips M, Waters TE, Sanderson CR. Prospective double-blind trial of duodenal ulcer relapse after eradication of Curnpylohacter pylori. Lancet 1988, 2, 1437-1442 Rauws EAJ, Tytgat GNJ. Cure of duodenal ulcer associated with eradication of H . p.vlori. Lancet 1990, 225, 1233-1235 Borsch G, Mai U, Opferkuch W. Oral triple therapy ( O n ) may effectively eradicate Cumpylohacterpylori (CP) in man: a pilot study. Gastroenterology 1988, 94(part II), A-248 Borody TJ, Cole P, Noonan S, Morgan A, Ossip G, Maysay J, Brandl S. Long-term Campyloharter. recurrence post eradication. Gastroenterology 1988, 94, A43
ISSN: 0036-5521 (Print) 1502-7708 (Online) Journal homepage: http://www.tandfonline.com/loi/igas20
Helicobacter pylori and Chronic Gastritis: An Increased Risk of Peptic Ulcer? A Review P. Sipponen To cite this article: P. Sipponen (1991) Helicobacter pylori and Chronic Gastritis: An Increased Risk of Peptic Ulcer? A Review, Scandinavian Journal of Gastroenterology, 26:sup186, 06-10, DOI: 10.3109/00365529109103980 To link to this article: http://dx.doi.org/10.3109/00365529109103980
Published online: 08 Jul 2009.
Submit your article to this journal
Article views: 6
View related articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=igas20 Download by: [University of Saskatchewan Library]
Date: 30 March 2016, At: 04:46
Helicobacter pylori and Chronic Gastritis: an Increased Risk of Peptic Ulcer? A Review P. SIPPONEN Dcpt. of Pathology, Jorvi Hospital, Espoo Finland
Sipponen P. Hdicohucter pylori and chronic gastritis: an increased risk of peptic ulcer? A review. Scand J Gastroenterol 1991, 26(suppl), 6-10
Downloaded by [University of Saskatchewan Library] at 04:46 30 March 2016
Key
MW~S:
Peptic ulcer; gastritis; Neli(nhucter pylori
Pentti Sipponcn. M.D.,Depr. of'Puthology, Jorvi Hospitul. SF-02740 E S ~ O OFinland , Fux: +3.78-0-86/2800
Probably more than 80%~of cases of chronic gastritis are associated with coexisting Helicohucter pylori (HP) infection (1 -3), and both the HP and the gastritis are strongly linked with peptic ulcer (4-lo), supporting the view that they have a relationship to the development of the ulcer disease (1 1-15). From the viewpoint of the pathogenesis of peptic ulcer, several statements and arguments can be presented concerning the participation of HP infection and gastritis in the sequence of events which at the worst culminate in ulcer.
H. pylori is the major muse of' chronic. gastritis Koch's postulates concerning the causal relationship between HP and gastritis seem to be satisfactorily fulfilled (16,17). In pracljce, the bacterium or antibodies against it are found in every case of chronic gastritis, at least in the early stages of the process. The bacterium can be isolated and grown in pure cultures from affected subjects, and the disease can be reproduced when the bacterium is inoculated into susceptible animals or volunteers. In addition, colloidal bismuth, together with various antimicrobial drugs, leads to the eradication of the bacterium in most of the infected patients (15), and the treatment leads to a reduction in the grade and extent of gastritis (3,lX). The acute inflammation ("activity" of the gastritis) disappears quickly after the eradication. The chronic inflammation diminishes in grade more slowly but will finally result in complete disappear-
ance of the gastritis.
Gastritis leads to utrophy of' the underlying mucosa The HP-induced gastritis results in a slow and gradual development of atrophy and metaplasia in the underlying mucosa in a great number of affected subjects (19-26). In the general population the appearance of cases with atrophy and intestinal tnetaplasia follows the appearance of cases with inflammation alone. On an average, the prevalence of cases with atrophy and metaplasia increases steadily with increasing age of the cohort. Correspondingly there occurs an increase in the extent of the atrophy and metaplasia in affected subjects with age. In the elderly, atrophy with accompanying metaplastic changes is a common finding and is found in a high proportion of subjects in the general population. The progression of gastritis to atrophic stages is probably not a uniform process (25),and may dissimilarly affect antrum and corpus in different individuals. Gastritis is slow in progression, may last for years or decades, and rarely heals spontaneously. In the course of time, some percentage of the HP-infected people will develop end-stages of the atrophic process, i.e., chronic gastritis with severe atrophy in the corpus or antral mucosa, or in both simultaneously. Atrophy implies a loss of normal glands, and consequently results in impairment of the gas-
Downloaded by [University of Saskatchewan Library] at 04:46 30 March 2016
H P , Gostritis and Peptic Ulcer
tric functions; for instance, in atrophy of the corpus mucosa it results in a low acid output, and in atrophy of the antral mucosa in a low rclease of gastrin from antral G cells (27,28). Evidence exists that the HP infection and the associated gastritis reduce resistance of the gastric mucosa, a phenomenon which may contribute to development of peptic ulcer and of other gastric diseases (see 5 ) . The HP-related enzymatic and toxic reactions, and a triggering of manifold immunological reactions in the gastric mucosa, as well as the local production of ammonia from endogenous urea by the bacterium, are some of the factors that may severely distort the mucosal integrity. The significance and details of these mechanisms are, however, still largely unknown. In regard to the risk of peptic ulcer, gastritis seems to exert a dual influence (29). In the genesis of peptic ulcer, gastritis may affect both the protective and the aggressive mechanisms, these influences being dependent upon the topography and grade of gastritis and atrophy in the stomach. The inflammation and the HP infection themselves may increase the risk of ulcer, whereas a marked atrophy in the corpus mucosa may decrease this risk by lowering the aggressive capacity of the acid-peptic factor.
a genetic property) the risk of peptic ulcer in antral gastritis may be even 50-fold that in subjects without these risk factors (30). Gastritis precedes peptic ulcer Available evidence indicates that chronic gastritis precedes the formation of peptic ulcer (42), suggesting that the gastritis is a real risk factor for peptic ulcer instead of being a simple result of the ulcer itself, This hypothesis of an HP-gastritis-ulcer sequence is supported by the long-term follow-up studies of patients with and without gastritis (42). These prospective studies demonstrate a remarkable cumulative rate of peptic ulcer in subjects with gastritis compared to subjects with normal stomach (both antral and corpus mucosa are normal) (Table I). In middle-aged males the 10-year cumulative risk of symptomatic peptic ulcer, of DU in particular, may exceed 20% in the antral gastritis (inflammation in antral mucosa only) or in the pangastritis (inflammation in both antral and corpus mucosa), whereas it is nearly zero in males with a normal stomach. Table I. Mean cumulative rate of DU or GU in a 10-year follow-up of male subjects with or without gastritis (source from ref. 42) Rate of DU or GU Histology
Risk of peptic ulcer is increased in gastritis Although gastritis is a common lesion in the general population, it is many times more prevalent in patients with peptic ulcer, and is associated almost invariably with both DU and GU if NSAID-induced ulcer cases are excluded (29-43). Studies carried out in Finland, Estonia and Poland (29,30) suggest that the risk Of peptic ulcer is high in the presence of chronic antral gastritis. The relative risk (RR) of DU or GU is On the average l o times higher in subjects with antral gastritis than in subjects with norsex In connection with the (gender is an independent risk factor for peptic ulcer) and non-secretor status (another independent risk factor; the subject does not secrete blood group substances in the gastric mucus -
7
Total
No.
("/u)
60
0
(0%)
Chronic antral gastritis
106
16
(15%)
Chronic corpus gastritis, or pangastritis with atropy of corpus mucosa
12
1
(8%)
Normal antrum and corpus
In contrast to the increased risk of peptic ulcer in antral gastritis or pangastritis, the risk of ulcer is low in the chronic corpus gastritisor in the pangastritis in which moderate or Severe atrophy of the corpus mucOSa coexists with the inflammation. This conclusion is by both cross-sectional and follow-up studies (29, 32,33,43). Furthermore, the inverse relationship between the ulcer risk and the grade of atrophy of the body gastritis appears logical when con-
8
P . Sipporieri
Table 11. Guidelines for interpretation of the risk of peptic ulcer in gastritis of different topographies and grades Histology
Interpretation
Nomial aiitrum and corpus
Risk of peptic ulcer is low and ulcer disease is improbable. Outputs of acid and pepsin are normal or high. HP is absent.
Chronic antnit gastritis
Cumulative risk of peptic ulcer is considerable, in middle-aged malcs in particular. Normal or high acid and pepsin outputs. HI' is practically always present and [he grade of HP colonisation is often high.
Chronic corpus gastritis or pangastritis with atrophy of corpus mucosa
Peptic ulcer disease improbable. Acid and pepsin outputs are low. HP is common but the grade 0 1 colonisation is usually low. Risk of pernicious anaemia if the atrophy is severe.
Downloaded by [University of Saskatchewan Library] at 04:46 30 March 2016
HP = Ildicobacrw p y h i
sidering the impairment in acid output in corpus atrophy, and this fits well with the functional consequences in the atrophy. Thus the atrophy is followed by low outputs of acid and pepsin, which correspondingly results in a decreased risk of peptic ulcer, irrespective of the presence and grade of the inflammation and HP infection in the antral mucosa. Gastric ulcer may occur, however, in subjects with marked atrophic changes and may be occasionally observed even in subjects with advanced corpus atrophy (32-34). A rapid development and progrcssion of corpus atrophy seems to occur in at least some of the patients with angular or high GU, in contrast to DU patients in whom corpus atrophy is rarely seen (44). In addition, the development of corpus atrophy in thc GU patients scems to modify the course of the disease. The long-term follow-up studies of Maaroos et al. (32) in Estonia have shown that the progression of corpus gastritis to advanced atrophic stages reduces the likelihood of active ulcer. It has been estimated (32) that the "life-span'' of the GU disease could be 10-15 years in these patients, during which time the acid-peptic factor will be reduced so that it no longer is able to overcome the protective mechanisms of the mucosa.
agement of peptic ulcer, bismuth and antibiotics provide new possibilities to handle HP infection, the strategy being the eradication of the HP infection with the aim to break the HPgastritis-ulcer scquence. Several trials (4548) have indeed shown that, in contrary to the traditional therapy, the eradication of the bacterium results in a long remission of the disease and in long-lasting prevention of ulcer recurrences. From the viewpoint of the HP-gastritis-ulcer sequence, peptic ulcer can be seen as a late complication of a H . pylori infection. There is evidence to suggest that in the multifactorial background of peptic ulcer disease, the HP infection and gastritis are indeed important and significant risk factors for the development of ulcer. In addition, in practical work the presence, type and grade of gastritis can be used in the interpretation of the risk of ulcer provided adequate specimens for microscopy are available from the antrum and corpus inucosa (Table 11).
I.
Marshall BJ, Warren JR. Unidcntified curved bacilli on gastric epithelium in the stomach of patients with gastritis and peptic ulceration. Lancet 1984, I , 121 I -
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