Scandinavian Journal of Gastroenterology
ISSN: 0036-5521 (Print) 1502-7708 (Online) Journal homepage: http://www.tandfonline.com/loi/igas20
Clinical Trials as Etiologic Research Tools in Helicobacter-Associated Gastritis P. Correa, B. Ruiz & F. Hunter To cite this article: P. Correa, B. Ruiz & F. Hunter (1991) Clinical Trials as Etiologic Research Tools in Helicobacter-Associated Gastritis, Scandinavian Journal of Gastroenterology, 26:sup181, 15-19, DOI: 10.3109/00365529109093203 To link to this article: http://dx.doi.org/10.3109/00365529109093203
Published online: 08 Jul 2009.
Submit your article to this journal
View related articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=igas20 Download by: [137.189.171.235]
Date: 23 March 2016, At: 14:59
Clinical Trials as Etiologic Research Tools in Helicobacter-Associated Gastritis P. CORREA, B. RUIZ & F. HUNTER Louisiana State University Medical Center, New Orleans, Louisiana. USA Correa P, Ruiz B, Hunter F. Clinical trials as etiologic research tools in Helicobacterassociated gastritis. Scand J Gastroenterol 1991, 26(suppl 181), 15-19 The role of clinical trials as tools to elucidate the etiology of chronic gastritis is discussed. Three areas are briefly explored. The first one concerns the classification of chronic gastritis, a constellation of interconnected nosologic entities. The second refers to the histopathologic factors of chronic gastritis; preliminary results show that clearance of Heiicobacterpylori decreases the inflammatory infiltrate and suggest that H. pylori alters cell ploidy. The third area refers to the multifactorial etiology of chronic gastritis and the role that clinical trials could play in its elucidation.
Downloaded by [] at 14:59 23 March 2016
P. Correa, M . D . , Dept. of Pathology, Louisiana State University Medical Cenrer, 1901 Perdido St., New Orleans, L A 70112, USA
sented in the table. Such is the case of infectious gastritis (that is, tuberculous and phlegmonous gastritis), eosinophilic gastritis, and entities of unknown etiology such as sarcoidosis. Recently, two specific types of gastritis have been recognized: ‘reflux’, ‘chemical’, or ‘reactive’ gastritis associated with duodenal reflux or nonsteroidal anti-inflammatory drugs, and ‘lymphocytic’ gastritis, possibly related to the malabsorption syndromes (2,3). The four entities in Table I have been described in detail, sometimes with different names, by several investigators. Biologic and epidemiologic characteristics, such as their gross and histologic features, population distribution, etiologic factors and sequelae, speak in favor of them being independent entities (4). The statistical association of H. pylori with chronic gastritis is undeniable. The role of the bacteria in different types of gastritis is, however, far from clear. The most consistent and strong association is between H . pylori and duodenal TYPES OF CHRONIC GASTRITIS From the etiopathogenic point of view, chronic ulcer. The latter is typically associated with diffuse gastritis can be classified as shown in Table I. The antral gastritis (DAG), characterized by dense four nosologic entities in Table I represent what interstitial lympho-plasmacytic infiltrate that has been called ‘simple’ or ‘nonspecific’ gastritis involves the full thickness of the antral mucosa. Of the two types of atrophic gastritis, only one, (1). Several specific entities have been recognized, are not controversial, and are not repre- multifocal atrophic gastritis (MAG), is associated
Clinical trials are most often used to determine the best treatment for a specific clinical condition. A considerable number of such trials is being carried out to determine the best treatment of Heficobacter-associated gastritis. The same epidemiologic techniques can be used to investigate etiologic associations between a specific agent and a specific disease or between the agent and specific biologic factors within one disease entity. In the case of Helicobacter-associated gastritis, clinical trials can be used to investigate some of the presently unclear features of the clinicopathologic entity or entities. Some of the issues that need resolution in this area are 1) the association of H. pylori with different types of chronic gastritis; 2) the association of H. pylori with the specific histopathologic components of gastritis; and 3) the association of H . pylori with other factors that may be involved in the etiology of gastritis.
16
P. Correa et al.
Table I. Classification of chronic gastritis Name Morphologic Not atrophic Superficial (SG) Diffuse antral (DAG)
Atrophic (gland loss) Diffuse corporal (DCG) Multifocal (MAG)
Mechanistic
Synonyms
Intial stage of
other types? Hypersecretory? Psychosomatic? Infectious? ( H . pylori)
Autoimmune? Dietary?
Antral,
type B. diffuse interstitial. follicular Type A
Environmental.
Downloaded by [] at 14:59 23 March 2016
type B, type AB. pangastritis
with H . pylori infection. Such gastritis, however, gastritis (SG)), which then penetrates to cover shows marked variation in H . pylori prevalence. the entire thickness of the mucosa. This fullIn populations with increased gastric cancer risk, thickness infiltrate has been called ‘atrophic or such as those of Narino, Colombia, the prevalence preatrophic’ gastritis. The term ‘atrophic’, of H . pylori infection in M A G is approximately however, is most frequently used to indicate gland 9 0 4 , whereas in the relatively lower risk popu- loss (8). The unitarian hypothesis then postulates lation o f the city of Cali. Colombia, the preva- that full-thickness mucosal infiltrate leads to lence is considerably lower. The atrophic gastritis metaplasia ( pseudopyloric o r intestinal). The associated with the pernicious anemia syndrome same hypothesis postulates that atrophy (gland (autoimmune or diffuse corporal gastritis (DCG)) loss) progresses with age in a similar fashion in is not usually associated with H . pylori infection patients with or without the pernicious anemia (5.6). syndrome (9). D A G and M A G are entirely different nosologic The reasons for collating all of the nosologic entities. but many ongoing clinical trials d o not entities represented in Table I into one unity are specify which gastritis is being treated. Some trials mostly historical and have to do with 1) obserrefer to their subjects as having ‘type B’ gastritis, vations based on Northern European, mostly a term that would exclude D A G because type-B Scandinavian, populations, in which both diffuse gastritis specifically refers to atrophic gastritis (7). corporal atrophic gastritis (DCG associated with The sets o f etiologic factors responsible for D A G the pernicious anemia syndrome) and MAG and MAG almost certainly have different com- (which is not related t o pernicious anemia) apparponents. The evaluation of the clinical trials could ently coincide (9). 2) The old notion that ‘peptic be confounded by factors that are pertinent to ulcer’ was one nosologic entity has been replaced one but not to the other type of gastritis. by the realization that there are at least two The present confusion in the classification of distinct entities: duodenal ulcer and gastric ulcer gastritis. which may result in difficulties in gen- (10, 11): it now appears clear that the chronic eralizing the results of clinical trials, is in part due gastritis accompanying the two ulcers are to the hypothesis that chronic gastritis is one different: D A G in duodenal ulcer and M A G in nosologic entity. This hypothesis postulates that gastric ulcer (1, 12). If the ‘unifying’ theory that the initial lesion is an inflammatory infiltrate of DAG, MAG, and DCG are one disease is the upper layers of the gastric mucosa (superficial accepted, the results of clinical trials carried out
Clinical Trials as Research Tools
17
Table 11. Inflammatory response B+N+M Infiltration
Hp+/Hp-
Sucralfate
Hp+/Hp+
Hp+/Hp-
Hp+ /Hp+
3 11
1 2
I 29
2 8
0 3
6 28
Polymorphonuclear neutrophilic 16 Decrease 2 No decrease Mononuclear Decrease No decrease
8 12
Downloaded by [] at 14:59 23 March 2016
B = bismuth subsalicylate: N = nitrofurantoin; M = metronidazole; and Hp+/Hpstatus before and after treatment.
=
Helicobacter pylori
mucin by the foveolar cells; d) increased cell replication (hyperplasia); e) gland loss (atrophy); and f) metaplasia (pseudopyloric and intestinal). Clinical trials oriented towards etiology and histopathology could contribute to clarify the role of H. pylori in each of the above factors. Preliminary results of our clinical trials illustrate this point. Table 11 shows preliminary results of a clinical trial comparing patients who at their first visit were positive for H . pylori in rapid urease test, culture, and Warthin-Starry stain. One group was treated for 4 weeks with bismuth subsalicilate, metronidazole, and nitrofurantoin, intended to eradicate H . pylori. The other group was treated with sucralfate, which has no known antibacterial effect. As can be seen in the table, clearance of H . pylori results in decreased PMN infiltration (89% versus 21%). It is also apparent, however, that in about 20% of the cases (8 of
in different populations (with disparate relative frequencies of the several entities) may be uninterpretable. There is no scientific evidence to support the notion that chronic gastritis represents a continuum within one nosologic entity. Clinical trials specifically addressing H. pylori infection, if combined with adequate histopathologic information, might contribute to better define the etiology and pathogenesis of the different types of chronic gastritis. HISTOPATHOLOGIC COMPONENTS OF GASTRITIS Of the many manifestations of the reaction of the gastric mucosa to injury, the following deserve special mention: a) polymorphonuclear neutrophilic (PMN) infiltrate; b) mononuclear (lympho-plasmacytic) infiltrate; c) loss of cytoplasmic
Table 111. PCNA-cyclin: average number of labeled antrum neck cells (%)
HP+/HP+
HP+/HPn
Treatment = B Visit 1 Visit 2
Mean
SE
+M +N
Treatment = sucralfate Visit 1 Visit 2
SE
Mean
n ~
~~
8 8
22.8 18.3
2.2 2.1
5 5
25.2 18.0
5.6 13
1
18.1 15.9
-
12 12
19.0 15.9
2.4 2.0
1
~~
B = bismuth subsalicylate; N = nitrofurantoin; M Helicobacter pylori status before and after treatment.
=
~~
metronidazole; SE = standard error; Hp+/Hp- =
18
P. Correa et al.
Table IV. NORs/50 nucleus antrum neck cells HP+/HP-
Treatment Visit 1 Visit 2 Treatment Visit 1 Visit 2
=
=
B
n
Mean
SE
n
Mean
SE
18 18
176.8 157.4*
8.8 8.6
12 12
172.7 196.6*
8.9 9.3
3 3
210.0 171.3
23.0 17.7
26 26
185.2 168.1
5.8 6.3
+M +N
sucralfate
* p < 0.05. B = bismuth subsalicylate; N
= nitrofurantoin; M Helicobacter pylori status before and after treatment.
Downloaded by [] at 14:59 23 March 2016
HP+/HP+
39) PMN infiltration decreased after sucralfate treatment, even though H . pylori persisted in the mucosa. The small number of cases makes this tinding uncertain. These experiments are far from being conclusive, but they suggest that this approach may help elucidate the role of PMNs in FI. pylori infection. It has been pointed out that PMN infiltration (so-called ‘activity’) is a good marker of H . pylori infection. This observation contrasts with some of the above observations and with the absence or scarcity of PMN infiltration in experimental animals infected with Helicobacter species (13.14). Table I1 also shows some very preliminary findings concerning lyniphocytic infiltration. The ‘chronic’ nature of this factor demands more prolonged observation to identify trends. Two cell replication variables were assessed in the same individuals. PCNA cyclin was evaluated with monoclonal antibodies against this protein, which specifically identifies cells in the S phase of the reproductive cycle. It therefore indicates the proportion o f cells undergoing cell division. A s shown in Table 111, no statistically significant trends are identified, which may reflect the small numbers of observations. The nucleolar organizer regions (NOR) reflect cell replication and ploidy (1 5). Even with the small number of cases shown in Table IV. a significantly lower N O R count is observed in subjects who cleared H . pylori than i n those who did not (157.4 versus 196.6). This very preliminary result suggests that H . pylori infection may induce ploidy abnormalities in replicating cells of the gastric epithelium.
=
metronidazole; SE
=
standard error; Hp+/Hp-
=
O T H E R FACTORS IN H . PYLORI-ASSOCIA T E D GASTRITIS It is generally accepted that most diseases are of multifactorial etiology. In the case of chronic gastritis, H. pylori is a major etiologic factor, but most probably not the only one. This idea is reinforced by the fact that the prevalence of H . pylori varies considerably between populations, even in individuals with similar types of chronic gastritis. Table V compares the prevalence of IgG anti-ti-pylori antibodies in two major types of gastritis for two Colombian populations. Pasto (Narino) displays a very high rate of gastric cancer, whereas Cali displays a lower rate. The prevalence of infection is much higher in Pasto than in Cali for each histopathologic type of gastritis. Epidemiologic studies of M A G have identified excessive salt intake and low consumption of fresh fruits and vegetables as risk factors (16, 17). It is therefore possible that the inter-
Table V. Seroprevalence (%) of IgG anti-If. pylori antibodies by histologic type of gastritis Colombia Cali
Pasto
~~
Diagnosis*
n
SG MAG All types
12 17 5
%
50 70 60
n
%
89 92 93
9 25 43
* SG = superficial gastritis; MAG atrophic gastritis.
,
=
multifocal
Clinical Trials as Research Tools
population differences in H . pylori prevalence reflect the interaction with other etiologic factors. Clinical trials could be designed to address the suspect etiologic factors, including H . pylori infection. ACKNOWLEDGEMENT This work was supported by Grants R01-A125590 and Pol-CA28842 from the National Institutes of Health. REFERENCES
Downloaded by [] at 14:59 23 March 2016
1. Correa P. Chronic gastritis: a clinico-pathological classification. Am J Gastroenterol 1988, 83, 504-
509 2. Dixon M, O’Connor H, Axon A , King R , Johnston D. Reflux gastritis: distinct histopathological entity? J Clin Pathol 1986, 39, 524-530 3. Haot J , Hamichi L, Wallez A, Mainguet P. Lymphocytic gastritis: a newly described entity, a retrospective endoscopic and histological study. Gut 1988, 29, 1258-1264 4. Correa P. Chronic gastritis: (non-specific). In: Whitehead R, ed. Gastrointestinal and oesophageal pathology. Churchill Livingstone, Edinburgh, 1989, 402420 5. O’Connor H, Axon A, Dixon M. Campylobacterlike organisms unusual in type A (pernicious anaemia) gastritis. Lancet 1984, 2, 1091 6. Flejou PF, Smith A, Stockbrugger R, Rode J, Price A. Pernicious anaemia and campylobacter like organisms: is the gastric antrum resistant to colonization? Gut 1989, 30, 6 M 4
19
7. Strickland R, Mackay R. A reappraisal of the nature and significance of chronic atrophic gastritis. Am J Dig Dis 1973, 18, 426-440 8. Magnus H. A re-assessment of the gastric lesion in pernicious anaemia. J Clin Patholl958,11,289-295 9. Siurala M, Sipponen P, Kekki M. Chronic gastritis: dynamic and clinical aspects. Scand J Gastroenterol 1985, 2O(suppl 109), 69-76 10. Stemmermann GN, Haenszel W, Locke F. Epidemiologic pathology of gastric ulcer and gastric carcinoma among Japanese in Hawaii. JNCI 1977, 58, 13-20 11. Boyd E, Wormsley K. Etiology and pathogenesis of peptic ulcer. In: Berk J , ed. Bockus gastroenterology. W. B. Saunders Co., Philadelphia, 1985, 101?-1059 12. Schindler R. Gastritis. In: Paulson M, ed. Gastroenterologic medicine. Lea and Febinger, Philadelphia, 1969, 687-709 13. Krakowka S, Morgan D , Kraft W, Teunk R. Establishment of gastric Campylobacter pylori infection in neonatal gnotobiotic piglet. Infect Immun 1987, 55,2789-2796 14. Newel1 D. Campylobacter pylori infections in nonhuman primates. In: Rathbone B, Heatley R, eds. Campylobacter pylori and gastroduodenal disease. Blackwell Scientific Publications, Oxford, 1989, 265-273 15. Suresh U, Chawner L, Buckley CH, Fox H. Do AgNOR counts reflect cellular ploidy or cellular proliferation? A study of trophoblastic tissue. J Pathol 1990, 106, 213-215 16. Nomura A , Yamakawa H, Ishidate T, et al. Intestinal metaplasia in Japan: Association with diet. JCNI 1982, 68, 401-405 17. Fontham E, Zavala D , Correa P, et al. Diet and chronicatrophic gastritis: a case-control study. JNCI 1986, 76, 621-627
ISSN: 0036-5521 (Print) 1502-7708 (Online) Journal homepage: http://www.tandfonline.com/loi/igas20
Clinical Trials as Etiologic Research Tools in Helicobacter-Associated Gastritis P. Correa, B. Ruiz & F. Hunter To cite this article: P. Correa, B. Ruiz & F. Hunter (1991) Clinical Trials as Etiologic Research Tools in Helicobacter-Associated Gastritis, Scandinavian Journal of Gastroenterology, 26:sup181, 15-19, DOI: 10.3109/00365529109093203 To link to this article: http://dx.doi.org/10.3109/00365529109093203
Published online: 08 Jul 2009.
Submit your article to this journal
View related articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=igas20 Download by: [137.189.171.235]
Date: 23 March 2016, At: 14:59
Clinical Trials as Etiologic Research Tools in Helicobacter-Associated Gastritis P. CORREA, B. RUIZ & F. HUNTER Louisiana State University Medical Center, New Orleans, Louisiana. USA Correa P, Ruiz B, Hunter F. Clinical trials as etiologic research tools in Helicobacterassociated gastritis. Scand J Gastroenterol 1991, 26(suppl 181), 15-19 The role of clinical trials as tools to elucidate the etiology of chronic gastritis is discussed. Three areas are briefly explored. The first one concerns the classification of chronic gastritis, a constellation of interconnected nosologic entities. The second refers to the histopathologic factors of chronic gastritis; preliminary results show that clearance of Heiicobacterpylori decreases the inflammatory infiltrate and suggest that H. pylori alters cell ploidy. The third area refers to the multifactorial etiology of chronic gastritis and the role that clinical trials could play in its elucidation.
Downloaded by [] at 14:59 23 March 2016
P. Correa, M . D . , Dept. of Pathology, Louisiana State University Medical Cenrer, 1901 Perdido St., New Orleans, L A 70112, USA
sented in the table. Such is the case of infectious gastritis (that is, tuberculous and phlegmonous gastritis), eosinophilic gastritis, and entities of unknown etiology such as sarcoidosis. Recently, two specific types of gastritis have been recognized: ‘reflux’, ‘chemical’, or ‘reactive’ gastritis associated with duodenal reflux or nonsteroidal anti-inflammatory drugs, and ‘lymphocytic’ gastritis, possibly related to the malabsorption syndromes (2,3). The four entities in Table I have been described in detail, sometimes with different names, by several investigators. Biologic and epidemiologic characteristics, such as their gross and histologic features, population distribution, etiologic factors and sequelae, speak in favor of them being independent entities (4). The statistical association of H. pylori with chronic gastritis is undeniable. The role of the bacteria in different types of gastritis is, however, far from clear. The most consistent and strong association is between H . pylori and duodenal TYPES OF CHRONIC GASTRITIS From the etiopathogenic point of view, chronic ulcer. The latter is typically associated with diffuse gastritis can be classified as shown in Table I. The antral gastritis (DAG), characterized by dense four nosologic entities in Table I represent what interstitial lympho-plasmacytic infiltrate that has been called ‘simple’ or ‘nonspecific’ gastritis involves the full thickness of the antral mucosa. Of the two types of atrophic gastritis, only one, (1). Several specific entities have been recognized, are not controversial, and are not repre- multifocal atrophic gastritis (MAG), is associated
Clinical trials are most often used to determine the best treatment for a specific clinical condition. A considerable number of such trials is being carried out to determine the best treatment of Heficobacter-associated gastritis. The same epidemiologic techniques can be used to investigate etiologic associations between a specific agent and a specific disease or between the agent and specific biologic factors within one disease entity. In the case of Helicobacter-associated gastritis, clinical trials can be used to investigate some of the presently unclear features of the clinicopathologic entity or entities. Some of the issues that need resolution in this area are 1) the association of H. pylori with different types of chronic gastritis; 2) the association of H. pylori with the specific histopathologic components of gastritis; and 3) the association of H . pylori with other factors that may be involved in the etiology of gastritis.
16
P. Correa et al.
Table I. Classification of chronic gastritis Name Morphologic Not atrophic Superficial (SG) Diffuse antral (DAG)
Atrophic (gland loss) Diffuse corporal (DCG) Multifocal (MAG)
Mechanistic
Synonyms
Intial stage of
other types? Hypersecretory? Psychosomatic? Infectious? ( H . pylori)
Autoimmune? Dietary?
Antral,
type B. diffuse interstitial. follicular Type A
Environmental.
Downloaded by [] at 14:59 23 March 2016
type B, type AB. pangastritis
with H . pylori infection. Such gastritis, however, gastritis (SG)), which then penetrates to cover shows marked variation in H . pylori prevalence. the entire thickness of the mucosa. This fullIn populations with increased gastric cancer risk, thickness infiltrate has been called ‘atrophic or such as those of Narino, Colombia, the prevalence preatrophic’ gastritis. The term ‘atrophic’, of H . pylori infection in M A G is approximately however, is most frequently used to indicate gland 9 0 4 , whereas in the relatively lower risk popu- loss (8). The unitarian hypothesis then postulates lation o f the city of Cali. Colombia, the preva- that full-thickness mucosal infiltrate leads to lence is considerably lower. The atrophic gastritis metaplasia ( pseudopyloric o r intestinal). The associated with the pernicious anemia syndrome same hypothesis postulates that atrophy (gland (autoimmune or diffuse corporal gastritis (DCG)) loss) progresses with age in a similar fashion in is not usually associated with H . pylori infection patients with or without the pernicious anemia (5.6). syndrome (9). D A G and M A G are entirely different nosologic The reasons for collating all of the nosologic entities. but many ongoing clinical trials d o not entities represented in Table I into one unity are specify which gastritis is being treated. Some trials mostly historical and have to do with 1) obserrefer to their subjects as having ‘type B’ gastritis, vations based on Northern European, mostly a term that would exclude D A G because type-B Scandinavian, populations, in which both diffuse gastritis specifically refers to atrophic gastritis (7). corporal atrophic gastritis (DCG associated with The sets o f etiologic factors responsible for D A G the pernicious anemia syndrome) and MAG and MAG almost certainly have different com- (which is not related t o pernicious anemia) apparponents. The evaluation of the clinical trials could ently coincide (9). 2) The old notion that ‘peptic be confounded by factors that are pertinent to ulcer’ was one nosologic entity has been replaced one but not to the other type of gastritis. by the realization that there are at least two The present confusion in the classification of distinct entities: duodenal ulcer and gastric ulcer gastritis. which may result in difficulties in gen- (10, 11): it now appears clear that the chronic eralizing the results of clinical trials, is in part due gastritis accompanying the two ulcers are to the hypothesis that chronic gastritis is one different: D A G in duodenal ulcer and M A G in nosologic entity. This hypothesis postulates that gastric ulcer (1, 12). If the ‘unifying’ theory that the initial lesion is an inflammatory infiltrate of DAG, MAG, and DCG are one disease is the upper layers of the gastric mucosa (superficial accepted, the results of clinical trials carried out
Clinical Trials as Research Tools
17
Table 11. Inflammatory response B+N+M Infiltration
Hp+/Hp-
Sucralfate
Hp+/Hp+
Hp+/Hp-
Hp+ /Hp+
3 11
1 2
I 29
2 8
0 3
6 28
Polymorphonuclear neutrophilic 16 Decrease 2 No decrease Mononuclear Decrease No decrease
8 12
Downloaded by [] at 14:59 23 March 2016
B = bismuth subsalicylate: N = nitrofurantoin; M = metronidazole; and Hp+/Hpstatus before and after treatment.
=
Helicobacter pylori
mucin by the foveolar cells; d) increased cell replication (hyperplasia); e) gland loss (atrophy); and f) metaplasia (pseudopyloric and intestinal). Clinical trials oriented towards etiology and histopathology could contribute to clarify the role of H. pylori in each of the above factors. Preliminary results of our clinical trials illustrate this point. Table 11 shows preliminary results of a clinical trial comparing patients who at their first visit were positive for H . pylori in rapid urease test, culture, and Warthin-Starry stain. One group was treated for 4 weeks with bismuth subsalicilate, metronidazole, and nitrofurantoin, intended to eradicate H . pylori. The other group was treated with sucralfate, which has no known antibacterial effect. As can be seen in the table, clearance of H . pylori results in decreased PMN infiltration (89% versus 21%). It is also apparent, however, that in about 20% of the cases (8 of
in different populations (with disparate relative frequencies of the several entities) may be uninterpretable. There is no scientific evidence to support the notion that chronic gastritis represents a continuum within one nosologic entity. Clinical trials specifically addressing H. pylori infection, if combined with adequate histopathologic information, might contribute to better define the etiology and pathogenesis of the different types of chronic gastritis. HISTOPATHOLOGIC COMPONENTS OF GASTRITIS Of the many manifestations of the reaction of the gastric mucosa to injury, the following deserve special mention: a) polymorphonuclear neutrophilic (PMN) infiltrate; b) mononuclear (lympho-plasmacytic) infiltrate; c) loss of cytoplasmic
Table 111. PCNA-cyclin: average number of labeled antrum neck cells (%)
HP+/HP+
HP+/HPn
Treatment = B Visit 1 Visit 2
Mean
SE
+M +N
Treatment = sucralfate Visit 1 Visit 2
SE
Mean
n ~
~~
8 8
22.8 18.3
2.2 2.1
5 5
25.2 18.0
5.6 13
1
18.1 15.9
-
12 12
19.0 15.9
2.4 2.0
1
~~
B = bismuth subsalicylate; N = nitrofurantoin; M Helicobacter pylori status before and after treatment.
=
~~
metronidazole; SE = standard error; Hp+/Hp- =
18
P. Correa et al.
Table IV. NORs/50 nucleus antrum neck cells HP+/HP-
Treatment Visit 1 Visit 2 Treatment Visit 1 Visit 2
=
=
B
n
Mean
SE
n
Mean
SE
18 18
176.8 157.4*
8.8 8.6
12 12
172.7 196.6*
8.9 9.3
3 3
210.0 171.3
23.0 17.7
26 26
185.2 168.1
5.8 6.3
+M +N
sucralfate
* p < 0.05. B = bismuth subsalicylate; N
= nitrofurantoin; M Helicobacter pylori status before and after treatment.
Downloaded by [] at 14:59 23 March 2016
HP+/HP+
39) PMN infiltration decreased after sucralfate treatment, even though H . pylori persisted in the mucosa. The small number of cases makes this tinding uncertain. These experiments are far from being conclusive, but they suggest that this approach may help elucidate the role of PMNs in FI. pylori infection. It has been pointed out that PMN infiltration (so-called ‘activity’) is a good marker of H . pylori infection. This observation contrasts with some of the above observations and with the absence or scarcity of PMN infiltration in experimental animals infected with Helicobacter species (13.14). Table I1 also shows some very preliminary findings concerning lyniphocytic infiltration. The ‘chronic’ nature of this factor demands more prolonged observation to identify trends. Two cell replication variables were assessed in the same individuals. PCNA cyclin was evaluated with monoclonal antibodies against this protein, which specifically identifies cells in the S phase of the reproductive cycle. It therefore indicates the proportion o f cells undergoing cell division. A s shown in Table 111, no statistically significant trends are identified, which may reflect the small numbers of observations. The nucleolar organizer regions (NOR) reflect cell replication and ploidy (1 5). Even with the small number of cases shown in Table IV. a significantly lower N O R count is observed in subjects who cleared H . pylori than i n those who did not (157.4 versus 196.6). This very preliminary result suggests that H . pylori infection may induce ploidy abnormalities in replicating cells of the gastric epithelium.
=
metronidazole; SE
=
standard error; Hp+/Hp-
=
O T H E R FACTORS IN H . PYLORI-ASSOCIA T E D GASTRITIS It is generally accepted that most diseases are of multifactorial etiology. In the case of chronic gastritis, H. pylori is a major etiologic factor, but most probably not the only one. This idea is reinforced by the fact that the prevalence of H . pylori varies considerably between populations, even in individuals with similar types of chronic gastritis. Table V compares the prevalence of IgG anti-ti-pylori antibodies in two major types of gastritis for two Colombian populations. Pasto (Narino) displays a very high rate of gastric cancer, whereas Cali displays a lower rate. The prevalence of infection is much higher in Pasto than in Cali for each histopathologic type of gastritis. Epidemiologic studies of M A G have identified excessive salt intake and low consumption of fresh fruits and vegetables as risk factors (16, 17). It is therefore possible that the inter-
Table V. Seroprevalence (%) of IgG anti-If. pylori antibodies by histologic type of gastritis Colombia Cali
Pasto
~~
Diagnosis*
n
SG MAG All types
12 17 5
%
50 70 60
n
%
89 92 93
9 25 43
* SG = superficial gastritis; MAG atrophic gastritis.
,
=
multifocal
Clinical Trials as Research Tools
population differences in H . pylori prevalence reflect the interaction with other etiologic factors. Clinical trials could be designed to address the suspect etiologic factors, including H . pylori infection. ACKNOWLEDGEMENT This work was supported by Grants R01-A125590 and Pol-CA28842 from the National Institutes of Health. REFERENCES
Downloaded by [] at 14:59 23 March 2016
1. Correa P. Chronic gastritis: a clinico-pathological classification. Am J Gastroenterol 1988, 83, 504-
509 2. Dixon M, O’Connor H, Axon A , King R , Johnston D. Reflux gastritis: distinct histopathological entity? J Clin Pathol 1986, 39, 524-530 3. Haot J , Hamichi L, Wallez A, Mainguet P. Lymphocytic gastritis: a newly described entity, a retrospective endoscopic and histological study. Gut 1988, 29, 1258-1264 4. Correa P. Chronic gastritis: (non-specific). In: Whitehead R, ed. Gastrointestinal and oesophageal pathology. Churchill Livingstone, Edinburgh, 1989, 402420 5. O’Connor H, Axon A, Dixon M. Campylobacterlike organisms unusual in type A (pernicious anaemia) gastritis. Lancet 1984, 2, 1091 6. Flejou PF, Smith A, Stockbrugger R, Rode J, Price A. Pernicious anaemia and campylobacter like organisms: is the gastric antrum resistant to colonization? Gut 1989, 30, 6 M 4
19
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