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Effect of Helicobacter pylori infection and eradication on gastric cell proliferation and apoptosis
A752 AGA ABSTRACTS
GASTROENTEROLOGY Vol. 118, No.4
4056
4058
DISTINCTIVE HISTOPATHOLOGICAL FEATURES IN H. pyLORI INFECTED INDIVIDUALS WITH FAMILY HISTORY OF GASTRIC CANCER. Antonia R. Sepulveda, Leif E. Peterson, Shelton Joseph, Sam Katherine, David Y. Graham, Gutierrez Oscar, Baylor Coli of Medicine, Houston, TX; Univ Nacional, Bogota, Colombia.
COMPARISON OF DIFFERENT METHODS FOR DETERMINATION OF PEPSINOGEN I AS A MARKER OF GASTRIC ATROPHY - CAN ELISA REPLACE RIA ? Gerhard Treiber, Andreas Leodolter, Manfred Nilius, Peter Malfertheiner, Univ Hosp, Magdeburg, Germany. Background: Pepsinogen I or Pepsinogen ratio (I1II) have been validated as serologic markers for diagnosis of atrophic gastritis which ....: may preceed gastric cancer. A pepsinogen ratio < 3.5 can be re.~ ;.~(.'.~~:: .; : .,"... "" garded as non-invasive gold stanx~ . (.' . dard for diagnosis of atrophy as previously shown by most studies. ;. : ' • '1'" : ; ' ) .: However values of pepsinogen I :~#~\" (~--:.~ : .. ;; : ,.: ' ';:.; :::: ', defining gastric atrophy vary widely between < 25 to < 70 ng/ml depending on population, assay, age, sex, smoking, protonpump-inhibitor cotherapy. Aims: To compare radioimmunoassay (RIA) with a new enzymeimmunoassay (ELISA). Methods: Sera from 232 H.pylori positive patients were obtained. An ELISA method (Gastroset POI, Orion, Espoo, Finland) and a RIA method (PEPSI-I and -II, DiaSorin, Saluccia, Italy) were used according to manufacturer's instructions. In the case of values above the upper calibration limit measurements after dilution of sera were repeated. A pepsinogen ratio below 3.5 or pepsinogen I values < 40 ng/ml (RIA and ELISA) were chosen for the purpose of this study in defining atrophy. Results: Correlation between RIA and ELISA for pepsinogen I was r=0.704, p
Background: Progression of H. pylori-associated gastritis is the main pathway for gastric cancer (GC) development. However, only some of the many individuals infected with H. pylori in the population develop gastric cancer, suggesting that other factors are main determinants of gastric cancer development. Host factors may represent genetic susceptibility traits that aggregate in families with gastric cancer, and might influence the outcome of H. pylori infection. Aims: To determine the role of family history of gastric cancer in the spectrum of histological changes of the gastric mucosa, and to identify specific patterns that may be useful to predict an increased risk of gastric cancer development. Methods: Histopathological changes associated with H. pylori infection were assessed in 110 individuals with family history of gastric cancer and in 77 without a history of gastric cancer in their families. All individuals were from Bogota, Colombia. Gastric biopsies using a standard 12-site (5 antrum, 6 corpus, I cardia) biopsy mapping protocol were obtained at endoscopy. Histological examination of each biopsy site after Genta stain was used to assess H. pylori, polymorphonuclear inflammation, mononuclear infiltration, lymphoid follicle load, intestinal metaplasia and atrophy using the updated Houston-scoring system. Repeated measures analysis of variance was used to compare the mean histopathological scores for each of the l2-biopsy sites from each patient across the two groups (positive family history vs. negative family history of GC). Results: H. pylori bacterial scores were significantly higher in the gastric corpus of younger individuals «36 years) with a positive family of gastric cancer (p=O.OI); antrum lymphoid follicle scores (p=O.OOI) and antrum atrophy scores (p=0.03) were also significantly higher in older individuals (2: 48 years) with a positive family history of Gc. Conclusions: Individuals with a family history of gastric cancer are associated with higher H. pylori load in the gastric corpus at early age. The continued high bacterial load may favor a higher degree of chronicity of the disease with accumulation of lymphoid follicles and more severe antral atrophic gastritis later in life. Because patients were from the same geographic region it is likely that H. pylori strains did not differ in the two groups and therefore the different pattern of host responses appear to be related to family traits that may confer susceptibility to gastric cancer development.
4057 GASTRIC METAPLASIA CHANGES AFTER 8 YEARS OF HELICOBACTER PYLORI ERADICATION IN A BLIND RANDOMIZED STUDY. Renzo R. Suriani, Giuseppe G. Rocca, Dario D. Mazzucco, Maurizio Dore, Ivo 1. Venturini, Enrico E. Cardesi, DEPT OF GASTROENTEROLOGY Hosp NUOVO, Rivoli, Italy; DEPT OF SPERIMENTAL GASTROENTEROLOGY, AZ Hosp MOLINETTE, Torino, Italy; DEPT OF GASTROENTEROLOGY, Hosp NUOVO, Rivoli, Italy; DEPT INTERNAL MEDICINE Hosp CIVILE, Susa, Italy; DEPT OF Pathology Hosp MARTINI, Torno, Italy. Aim: to determine if Helicobacter pylori (Hp) eradication modify antrum gastric atrophy and metaplasia. Methods: prospectively we studied 2 groups of duodenal ulcers Hp positive pts (Group 1: 16 pts, mean age 47, rn/f 13/3)-(Group 2: 22 pts, mean age 53, rn/f 16/6), before and after randomisation to placebo (Group I, mean :t: standard deviation (mean :t: SO): II :t: 22 and 59 :t: 40 months) or antibiotics (Group 2 mean :t: SO: 13 :t: 22 and 87 :t: 29 months). The Group 2 pts were persitently Hp negative after therapy. Two biopsy at the antrum were taken at each andoscopy (Group 1 mean :t: SD: 11 :t: 4 /pts, Group 2: 18 :t: 3/pts). The gastritis was blind scored 0 to 3 for Chronic-Inactive (CI), Chronic-Active (CA), Atrophic (AT) and Metaplasia (ME) from the same pathologist (Score Classification). 976 biopsy samples were scored. We classified also the types of gastritis as Increased, Decreased or Fluctuate when was judged to rise, fall or vary irregularly (Mode Classification). The Mann-Whitney U test was performed on both Score and Mode classifications. Given the long follow-up, data were also analysed as time-to-event with the Kaplan-Meier non parametric methods. Results: no difference was found on gastritis in Group 1 and 2 before randomisation. After therapy only CI and CA were different on score (p = 0.00) and on Decreased Mode classifications (p = 0.(0) at Mann Whitney cross sectional analysis. However difference of AT, ME and CI gastritis on Fluctuate Mode was found with survival analysis (sas System-Long Rank). Discussion: Hp eradication decrease antrum CNCI gastritis and modifies Atrophy, and Metaplasia. When the time-toevent component is correctly taken into account the gastric metaplasia is markedly different and open to new and more interesting interpretations.
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4059 EFFECT OF HELICOBACTER PYLORI INFECTION AND ERADICATION ON GASTRIC CELL PROLIFERATION AND APOPTOSIS. Zsuzsa Unger, Bela Molnar, Laszlo Pronay, Zsolt Tulassay, Semmelweis Med Sch, II Dept of Medicine, Budapest, Hungary. Background: Data concerning the correlation between Helicobacter pylori infection and gastric epithelial cell proliferation and apoptotic activity (non-necrotic, programmed cell death) is still controversial. Aim of the study: Evaluation of Helicobacter pylori infection on cell kinetic parameters in normal gastric epithelia, gastritis with/without intestinal metaplasia and carcinoma. Patients and methods: Antral biopsies were taken from 121 patients (61 women, 60 men, mean age 58,5 y.o. (range 22-89». Sections were scored for normal epithelia (n=15), gastritis without intestinal metaplasia (n=74), gastritis with intestinal metaplasia (n=24) and gastric carcinoma (n= 8). 52 patients had H. pylori positive gastritis, and success of eradication therapy was controlled in 34 cases. To characterize cell proliferation an immunohistochemistry (PCNA) and histochemistry method (AgNOR) was used and to assess apoptosis TUNEL (terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridinetriphosphate (dUTP) nick end-labeling) was used. Results: Results of PCNA and AgNOR significantly correlated except of that in the intestinal metaplasia group. PCNA LI (54,79 + 19,1 vs. 53,20 + 20,7) and AgNOR counts (291,43 + 44,3 vs. 277,8 + 57,54) were not different in H.pylori positive and negative gastritis. However the apoptotic index (AI) (0,0215 + 0,012 vs. 0,Q\8 + 0,0(03) was higher, in the presence of H. pylori. The H. pylori infection caused significant increase in proliferation rate and lower apoptotic activity (AI: 0,015) in intestinal metaplasia group as compared to the negative ones. In this group of intestinal metaplasisa the proliferation activity decreased (LI before therapy: 50,865 + 19,96, LI after successful therapy: 46,17 + 26,44) to the activity of the normal epithelia after the successful eradication, but remained high if eradication therapy failed. The apoptotic activity increased in cases of successful therapy, as well. Conclusions: H.pylori infection can cause ulceration in gastritis without intestinal metaplasia through increased apoptosis. The intestinal metaplasia cases show increased cell proliferation and decreased apoptosis in H.pylori infection. Successful eradication recreates healthy cell kinetic ratios.
GASTROENTEROLOGY Vol. 118, No.4
4056
4058
DISTINCTIVE HISTOPATHOLOGICAL FEATURES IN H. pyLORI INFECTED INDIVIDUALS WITH FAMILY HISTORY OF GASTRIC CANCER. Antonia R. Sepulveda, Leif E. Peterson, Shelton Joseph, Sam Katherine, David Y. Graham, Gutierrez Oscar, Baylor Coli of Medicine, Houston, TX; Univ Nacional, Bogota, Colombia.
COMPARISON OF DIFFERENT METHODS FOR DETERMINATION OF PEPSINOGEN I AS A MARKER OF GASTRIC ATROPHY - CAN ELISA REPLACE RIA ? Gerhard Treiber, Andreas Leodolter, Manfred Nilius, Peter Malfertheiner, Univ Hosp, Magdeburg, Germany. Background: Pepsinogen I or Pepsinogen ratio (I1II) have been validated as serologic markers for diagnosis of atrophic gastritis which ....: may preceed gastric cancer. A pepsinogen ratio < 3.5 can be re.~ ;.~(.'.~~:: .; : .,"... "" garded as non-invasive gold stanx~ . (.' . dard for diagnosis of atrophy as previously shown by most studies. ;. : ' • '1'" : ; ' ) .: However values of pepsinogen I :~#~\" (~--:.~ : .. ;; : ,.: ' ';:.; :::: ', defining gastric atrophy vary widely between < 25 to < 70 ng/ml depending on population, assay, age, sex, smoking, protonpump-inhibitor cotherapy. Aims: To compare radioimmunoassay (RIA) with a new enzymeimmunoassay (ELISA). Methods: Sera from 232 H.pylori positive patients were obtained. An ELISA method (Gastroset POI, Orion, Espoo, Finland) and a RIA method (PEPSI-I and -II, DiaSorin, Saluccia, Italy) were used according to manufacturer's instructions. In the case of values above the upper calibration limit measurements after dilution of sera were repeated. A pepsinogen ratio below 3.5 or pepsinogen I values < 40 ng/ml (RIA and ELISA) were chosen for the purpose of this study in defining atrophy. Results: Correlation between RIA and ELISA for pepsinogen I was r=0.704, p
Background: Progression of H. pylori-associated gastritis is the main pathway for gastric cancer (GC) development. However, only some of the many individuals infected with H. pylori in the population develop gastric cancer, suggesting that other factors are main determinants of gastric cancer development. Host factors may represent genetic susceptibility traits that aggregate in families with gastric cancer, and might influence the outcome of H. pylori infection. Aims: To determine the role of family history of gastric cancer in the spectrum of histological changes of the gastric mucosa, and to identify specific patterns that may be useful to predict an increased risk of gastric cancer development. Methods: Histopathological changes associated with H. pylori infection were assessed in 110 individuals with family history of gastric cancer and in 77 without a history of gastric cancer in their families. All individuals were from Bogota, Colombia. Gastric biopsies using a standard 12-site (5 antrum, 6 corpus, I cardia) biopsy mapping protocol were obtained at endoscopy. Histological examination of each biopsy site after Genta stain was used to assess H. pylori, polymorphonuclear inflammation, mononuclear infiltration, lymphoid follicle load, intestinal metaplasia and atrophy using the updated Houston-scoring system. Repeated measures analysis of variance was used to compare the mean histopathological scores for each of the l2-biopsy sites from each patient across the two groups (positive family history vs. negative family history of GC). Results: H. pylori bacterial scores were significantly higher in the gastric corpus of younger individuals «36 years) with a positive family of gastric cancer (p=O.OI); antrum lymphoid follicle scores (p=O.OOI) and antrum atrophy scores (p=0.03) were also significantly higher in older individuals (2: 48 years) with a positive family history of Gc. Conclusions: Individuals with a family history of gastric cancer are associated with higher H. pylori load in the gastric corpus at early age. The continued high bacterial load may favor a higher degree of chronicity of the disease with accumulation of lymphoid follicles and more severe antral atrophic gastritis later in life. Because patients were from the same geographic region it is likely that H. pylori strains did not differ in the two groups and therefore the different pattern of host responses appear to be related to family traits that may confer susceptibility to gastric cancer development.
4057 GASTRIC METAPLASIA CHANGES AFTER 8 YEARS OF HELICOBACTER PYLORI ERADICATION IN A BLIND RANDOMIZED STUDY. Renzo R. Suriani, Giuseppe G. Rocca, Dario D. Mazzucco, Maurizio Dore, Ivo 1. Venturini, Enrico E. Cardesi, DEPT OF GASTROENTEROLOGY Hosp NUOVO, Rivoli, Italy; DEPT OF SPERIMENTAL GASTROENTEROLOGY, AZ Hosp MOLINETTE, Torino, Italy; DEPT OF GASTROENTEROLOGY, Hosp NUOVO, Rivoli, Italy; DEPT INTERNAL MEDICINE Hosp CIVILE, Susa, Italy; DEPT OF Pathology Hosp MARTINI, Torno, Italy. Aim: to determine if Helicobacter pylori (Hp) eradication modify antrum gastric atrophy and metaplasia. Methods: prospectively we studied 2 groups of duodenal ulcers Hp positive pts (Group 1: 16 pts, mean age 47, rn/f 13/3)-(Group 2: 22 pts, mean age 53, rn/f 16/6), before and after randomisation to placebo (Group I, mean :t: standard deviation (mean :t: SO): II :t: 22 and 59 :t: 40 months) or antibiotics (Group 2 mean :t: SO: 13 :t: 22 and 87 :t: 29 months). The Group 2 pts were persitently Hp negative after therapy. Two biopsy at the antrum were taken at each andoscopy (Group 1 mean :t: SD: 11 :t: 4 /pts, Group 2: 18 :t: 3/pts). The gastritis was blind scored 0 to 3 for Chronic-Inactive (CI), Chronic-Active (CA), Atrophic (AT) and Metaplasia (ME) from the same pathologist (Score Classification). 976 biopsy samples were scored. We classified also the types of gastritis as Increased, Decreased or Fluctuate when was judged to rise, fall or vary irregularly (Mode Classification). The Mann-Whitney U test was performed on both Score and Mode classifications. Given the long follow-up, data were also analysed as time-to-event with the Kaplan-Meier non parametric methods. Results: no difference was found on gastritis in Group 1 and 2 before randomisation. After therapy only CI and CA were different on score (p = 0.00) and on Decreased Mode classifications (p = 0.(0) at Mann Whitney cross sectional analysis. However difference of AT, ME and CI gastritis on Fluctuate Mode was found with survival analysis (sas System-Long Rank). Discussion: Hp eradication decrease antrum CNCI gastritis and modifies Atrophy, and Metaplasia. When the time-toevent component is correctly taken into account the gastric metaplasia is markedly different and open to new and more interesting interpretations.
",
'~.' ,.' ';
4059 EFFECT OF HELICOBACTER PYLORI INFECTION AND ERADICATION ON GASTRIC CELL PROLIFERATION AND APOPTOSIS. Zsuzsa Unger, Bela Molnar, Laszlo Pronay, Zsolt Tulassay, Semmelweis Med Sch, II Dept of Medicine, Budapest, Hungary. Background: Data concerning the correlation between Helicobacter pylori infection and gastric epithelial cell proliferation and apoptotic activity (non-necrotic, programmed cell death) is still controversial. Aim of the study: Evaluation of Helicobacter pylori infection on cell kinetic parameters in normal gastric epithelia, gastritis with/without intestinal metaplasia and carcinoma. Patients and methods: Antral biopsies were taken from 121 patients (61 women, 60 men, mean age 58,5 y.o. (range 22-89». Sections were scored for normal epithelia (n=15), gastritis without intestinal metaplasia (n=74), gastritis with intestinal metaplasia (n=24) and gastric carcinoma (n= 8). 52 patients had H. pylori positive gastritis, and success of eradication therapy was controlled in 34 cases. To characterize cell proliferation an immunohistochemistry (PCNA) and histochemistry method (AgNOR) was used and to assess apoptosis TUNEL (terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridinetriphosphate (dUTP) nick end-labeling) was used. Results: Results of PCNA and AgNOR significantly correlated except of that in the intestinal metaplasia group. PCNA LI (54,79 + 19,1 vs. 53,20 + 20,7) and AgNOR counts (291,43 + 44,3 vs. 277,8 + 57,54) were not different in H.pylori positive and negative gastritis. However the apoptotic index (AI) (0,0215 + 0,012 vs. 0,Q\8 + 0,0(03) was higher, in the presence of H. pylori. The H. pylori infection caused significant increase in proliferation rate and lower apoptotic activity (AI: 0,015) in intestinal metaplasia group as compared to the negative ones. In this group of intestinal metaplasisa the proliferation activity decreased (LI before therapy: 50,865 + 19,96, LI after successful therapy: 46,17 + 26,44) to the activity of the normal epithelia after the successful eradication, but remained high if eradication therapy failed. The apoptotic activity increased in cases of successful therapy, as well. Conclusions: H.pylori infection can cause ulceration in gastritis without intestinal metaplasia through increased apoptosis. The intestinal metaplasia cases show increased cell proliferation and decreased apoptosis in H.pylori infection. Successful eradication recreates healthy cell kinetic ratios.