Chronic Inflammation Scores Research Articles

Histological changes in the gastric mucosa after Helicobacter pylori eradication.

Correa described a stepwise model of changes in the gastric mucosa after Helicobacter pylori infection, from the normal gastric epithelium to chronic gastritis, atrophy, intestinal metaplasia, dysplasia and adenocarcinoma. The aim of this study is to assess the reversibility of these mucosal changes after H. pylori eradication. The study sample consisted of 89 patients who underwent at least two gastric biopsies from 1990 to 2000, with a positive finding for H. pylori in the first and a negative finding in the second. Specimens were evaluated for acute and chronic inflammation, lymphoid aggregates, proliferation, mucosal atrophy, intestinal metaplasia, dysplasia, and MUC5AC and MUC6 expression using histochemical and immunohistochemical methods. The average time between biopsies was 23.15 +/- 26.30 months. There was a significant decrease in acute and chronic inflammation scores, from 1.48 +/- 1.10 to 0.23 +/- 0.63 and from 2.67 +/- 0.68 to 1.44 +/- 1.04, respectively (P < 0.001), and in a number of lymphoid follicles, from 42.68% to 21.95% of cases (P < 0.008). The number of glands increased from 39.08 +/- 16.67/mm to 48.86 +/- 17.93/mm after eradication (P = 0.062). Intestinal metaplasia was found in 17.07% of the cases, with no change over time. Dysplasia appeared in one case 2 years after eradication. In 27 patients, the Ki67 labeling index decreased significantly after eradication, while MUC5AC and MUC6 expression increased. Our findings, although not conclusive for arrest of the malignant potential, support the importance of H. pylori eradication in the prevention of gastric cancer.

Hypergastrinemia after Helicobacter pylori infection is associated with bacterial load and related inflammation of the oxyntic corpus mucosa.

Helicobacter pylori infection causes hypergastrinemia. This study aimed to determine the association between serum gastrin and the severity of H. pylori-related gastric histology. A total of 458 dyspeptic patients were included in this study after the absence of gastric malignancy was confirmed using endoscopy. The gastric specimens of each patient were collected from the antrum and corpus for the analysis of H. pylori-related histology changes by updated Sydney's system. Before endoscopy, the fasting blood samples were collected for gastrin analysis. The H. pylori-infected patients had higher gastrin levels than those without infection (P = 0.01). Gastrin levels were related to H. pylori density and acute and chronic inflammation scores in the corpus mucosa (P < 0.05), but not in the antral mucosa (P = NS). Gastrin levels were also not related to the presence of gastric atrophy. Multivariate regression showed that the gastrin level was only related to acute corpus inflammation. However, in the patients without infection, the gastrin level was also associated with acute corpus inflammation. Nevertheless, the patients with denser H. pylori infection were more likely to have acute corpus gastritis than those with lighter H. pylori infection, and thus presented with higher gastrin levels (P < 0.05). The increased level of gastrin of serum after H. pylori infection was associated with acute inflammation in the gastric corpus mucosa, but not in the antral mucosa. Denser H. pylori infection causes more severe corpus gastritis and thus may lead to a higher fasting level of gastrin of serum.

Mucin Phenotype and Background Mucosa of Intramucosal Differentiated-Type Adenocarcinoma of the Stomach

Objectives: Gastric carcinomas have been divided into differentiated (intestinal) and undifferentiated (diffuse) types. Recently, classification studies based on mucin expression have revealed that some differentiated-type carcinomas are of a gastric phenotype. In this study, we investigated the clinicopathological features of differentiated-type adenocarcinomas and evaluated the background mucosa of the stomach based on mucin expression by the tumors. Methods: Seventy-six intramucosal differentiated-type adenocarcinomas of the stomach were evaluated macroscopically and histologically. The mucin expression of tumor cells was examined by immunohistochemical staining with monoclonal antibodies against human gastric mucin (45M1), class III mucin (HIK1083), small intestinal mucinous antigen (SIMA-4D3), and MUC2 (Ccp58). Tumors were classified by phenotype as gastric (G-type), intestinal (I-type), mixed (M-type), or null (N-type). Not only the clinicopathological features but also the background mucosa of the stomach of G-type and I-type carcinomas were compared histologically and serologically. Results: Seventeen tumors (22.4%) were classified as G-type, 31 (40.8%) as I-type, 22 (28.9%) as M-type, and 6 (7.9%) as N-type. The frequencies of elevated type tumors and papillary adenocarcinomas and the ratio of moderately/well-differentiated adenocarcinomas were higher in G-type than in I-type carcinomas. The scores for glandular atrophy and intestinal metaplasia were higher and the scores for chronic inflammation, polymorphonuclear neutrophil activity, and the density of Helicobacter pylori were lower in G-type than in I-type tumors. The serum level of pepsinogen I and the pepsinogen I/II ratio were significantly lower in G-type than in I-type tumors. Conclusions: G-type carcinoma is the predominant phenotype of papillary adenocarcinoma. The background mucosa of G-type carcinoma is associated with glandular atrophy and intestinal metaplasia, whereas that of I-type carcinoma is associated with active and chronic inflammation induced by H. pylori infection.

RDP58, a locally active TNF inhibitor, is effective in the dextran sulphate mouse model of chronic colitis.

RDP58 is a novel anti-inflammatory peptide that inhibits TNF synthesis and upregulates heme oxygenase-1. RDP58 therapy was evaluated in the dextran sodium sulphate (DSS) model of chronic colitis. Colitis was induced by giving DSS to mice (n = 8 animals/group). Toxicity studies were done in Rhesus monkeys (n = 5), dogs (n = 3) and mice (n = 10). In colitis, mice were treated with p.o. vehicle (saline), RDP58 (5 and 10 mg/kg/day) or 5-ASA (50 mg/kg/day). Disease activity index (DAI) was used as the endpoint of efficacy. RDP58 therapy significantly reduced DAI and histological scores in all animals. DAI scores in RDP58 treated animals declined faster than 5-ASA. RDP58 at 5 or 10 mg/ kg/day significantly reduced DAI compared to 5-ASA. RDP58 significantly reduced acute, chronic and total inflammation scores. It enhanced re-epithelialization by reducing crypt scores. RDP58 was not bioavailable and was well tolerated. Therapeutic efficacy of RDP58 combined with a lack of bioavailibility and toxicity suggest that RDP58 may be a promising new therapeutic for IBD.

Variation in serum pepsinogens with severity and topography of Helicobacter pylori-associated chronic gastritis in dyspeptic patients referred for endoscopy.

It has long been recognised that specific patterns of gastritis are linked with different gastroduodenal diseases and that serum pepsinogens vary with the histological state of the gastric mucosa. With the discovery of the role of Helicobacter pylori in chronic gastritis and the availability of noninvasive tests for H. pylori infection, individuals with H. pylori gastritis can now be identified without endoscopic biopsy. However, without a knowledge of the pattern and severity of gastritis it is impossible to predict the likelihood of significant associated gastroduodenal pathology. The aim of this study was to evaluate the diagnostic potential of serum pepsinogens I and II in predicting the topography and severity of gastritis in H. pylori-infected dyspeptic patients attending for endoscopy. Fasting serum was obtained from consecutive dyspeptic patients attending for endoscopy, and pairs of gastric biopsies obtained from the mid-body and antrum. Gastritis was graded according to the Sydney System, and serum pepsinogen levels determined by radio-immunoassay. Sixty-nine dyspeptic patients were studied (mean age: 49.6 years) of whom 34 had H. pylori-associated chronic gastritis (Hp-gastritis) - antral predominant gastritis (APG) in 41.2%, pangastritis (PAN) in 52.9%, and corpus predominant (CPG) in 5.9%. Serum pepsinogen II levels were significantly higher, and the serum pepsinogen I : II ratio significantly lower, in the H. pylori positive group than in other groups. Within the Hp-gastritis group, there was a step-wise decrease in serum pepsinogen I levels with progression from APG through PAN to CPG pattern (a cut-off value of > or = 100 ng/ml would have identified APG with a positive predictive value of 77%, though with low sensitivity). Within the Hp-gastritis group, serum pepsinogen I and II levels were correlated with antral chronic inflammation score and serum pepsinogen II levels also with antral activity score. Serum pepsinogen I and the pepsinogen I : II ratio were lowest in severe gastric corpus atrophy. In dyspeptic patients known to be infected with H. pylori, serum pepsinogen values provide an assessment of the overall topography of gastritis, the severity of antral inflammation and the presence of severe corpus atrophy.

The association between CagA status and the development of esophagitis after the eradication of helicobacter pylori

BACKGROUND: Strains of Helicobacter pylori with the cytotoxine-associated gene A ( cagA) are linked to severe forms of gastroduodenal disease. Although eradication of H. pylori may predispose to the development of reflux esophagitis, the effects of CagA status on risk of esophagitis after successful H. pylori treatment are not known. METHODS: We studied 50 consecutive patients without esophagitis in whom H. pylori was eradicated successfully. CagA status was determined by immunoblotting sera from patients against H. pylori antigens. Patients underwent upper gastrointestinal endoscopy before eradication and 6, 12, 18, and 24 months after eradication or when reflux symptoms occurred. Biopsy specimens of the antrum and corpus were evaluated for gastritis before H. pylori eradication and at the end of the study. The sum of the scores for acute and chronic inflammation (both measured on a 0 [absent] to 3 [severe] scale) comprised the total gastritis severity score. RESULTS: In a multivariate proportional hazards regression analysis, positive CagA serology (hazard ratio [HR] = 10, 95% confidence interval [CI]: 1.3 to 81) and moderate-to-severe corpus gastritis (total severity score ≥4) before eradication (HR = 2.3, 95% CI: 1.2 to 6.1) were independent risk factors for the development of esophagitis after H. pylori eradication. CONCLUSION: Patients infected with strains of H. pylori that are cagA-positive are at increased risk of developing esophagitis after eradication of H. pylori.

Cyclooxygenase-2 expression in gastric antral mucosa before and after eradication of Helicobacter pylori infection.

Helicobacter pylori (H. pylori) causes chronic gastritis. The inducible prostaglandin synthetase cyclooxygenase 2 (COX-2) plays an important role in inflammatory conditions. We hypothesized that H. pylori-associated chronic gastritis would express COX-2 protein. Our aim was to evaluate the effect of eradication of H. pylori infection on COX-2 expression in the antral mucosa of patients before and after antibiotic therapy. Tissues were obtained from patients with non-ulcer dyspepia undergoing H. pylori eradication. Ten patients with proven H. pylori infection and subsequent successful eradication were studied. Three biopsies of antral mucosa were evaluated before and after H. pylori eradication. The amount of acute and chronic inflammation was quantitated. Immunohistochemical staining for COX-2 was expressed as a percentage of the total number of cells and correlated with the degree of chronic inflammation. Specific immunostaining for COX-2 was observed in antral mucosa of patients infected with H. pylori. Patchy cytoplasmic staining was seen in surface epithelial cells and strong cytoplasmic staining for COX-2 was seen in parietal cells. Spotty cytoplasmic staining for COX-2 was also seen in lamina propria plasma cells, as well as there being macrophages present in the germinal centers of lymphoid aggregates. COX-2 expression could be detected both before and after eradication of H. pylori. The mean percentage of cells staining for COX-2 was significantly higher in H. pylori-infected mucosa, compared with mucosa after successful H. pylori eradication (33.4% +/- 5.4 vs 18.9% +/- 3.3, p = 0.038). COX-2 immunostaining correlated best with the chronic inflammation score (r2 = 0.78, p < 0.001). There was a strong correlation for those subjects who were H. pylori infected, as well as for those who had successful H. pylori eradication. H. pylori associated acute and chronic antral inflammation was associated with immunohistochemical detection of COX-2 protein in epithelial cells, in addition to associated mononuclear cells and parietal cells. Expression was reduced, but not eliminated, in the epithelium after successful eradication of H. pylori. Despite the reduction in COX-2 expression after H. pylori eradication, expression of COX-2 in epithelial cells remained and strongly correlated with the extent of the chronic inflammatory cell infiltrate. The clinical implications of H. pylori-associated induction of COX-2 expression for patients on selective COX-2 inhibitors, in addition to the role of COX-2 in gastric carcinogenesis, deserve further study.

Cyclooxygenase-2 expression in gastric antral mucosa before and after eradication of Helicobacter pylori infection

OBJECTIVE: Helicobacter pylori ( H. pylori) causes chronic gastritis. The inducible prostaglandin synthetase cyclooxygenase 2 (COX-2) plays an important role in inflammatory conditions. We hypothesized that H. pylori-associated chronic gastritis would express COX-2 protein. Our aim was to evaluate the effect of eradication of H. pylori infection on COX-2 expression in the antral mucosa of patients before and after antibiotic therapy. METHODS: Tissues were obtained from patients with nonulcer dyspepia undergoing H. pylori eradication. Ten patients with proven H. pylori infection and subsequent successful eradication were studied. Three biopsies of antral mucosa were evaluated before and after H. pylori eradication. The amount of acute and chronic inflammation was quantitated. Immunohistochemical staining for COX-2 was expressed as a percentage of the total number of cells and correlated with the degree of chronic inflammation. RESULTS: Specific immunostaining for COX-2 was observed in antral mucosa of patients infected with H. pylori. Patchy cytoplasmic staining was seen in surface epithelial cells and strong cytoplasmic staining for COX-2 was seen in parietal cells. Spotty cytoplasmic staining for COX-2 was also seen in lamina propria plasma cells, as well as there being macrophages present in the germinal centers of lymphoid aggregates. COX-2 expression could be detected both before and after eradication of H. pylori. The mean percentage of cells staining for COX-2 was significantly higher in H. pylori-infected mucosa, compared with mucosa after successful H. pylori eradication (33.4% ± 5.4 vs 18.9% ± 3.3, p = 0.038). COX-2 immunostaining correlated best with the chronic inflammation score (r 2 = 0.78, p < 0.001). There was a strong correlation for those subjects who were H. pylori infected, as well as for those who had successful H. pylori eradication. CONCLUSIONS: H. pylori associated acute and chronic antral inflammation was associated with immunohistochemical detection of COX-2 protein in epithelial cells, in addition to associated mononuclear cells and parietal cells. Expression was reduced, but not eliminated, in the epithelium after successful eradication of H. pylori. Despite the reduction in COX-2 expression after H. pylori eradication, expression of COX-2 in epithelial cells remained and strongly correlated with the extent of the chronic inflammatory cell infiltrate. The clinical implications of H. pylori-associated induction of COX-2 expression for patients on selective COX-2 inhibitors, in addition to the role of COX-2 in gastric carcinogenesis, deserve further study.

Clinical Correlations of Patterns of Placental Pathology in Preterm Pre-eclampsia

The objective of this study was to determine if placental histopathology patterns are associated with clinical features of preterm pre-eclampsia. A 1989-1993 database of consecutive non-anomalous singleton livebirths delivered at 22-32 weeks gestation excluding cases of maternal diabetes mellitus and chronic hypertension included 74 cases of pre-eclampsia. Placentae were scored for uteroplacental vascular lesions and lesions of chronic inflammation and coagulation. Thirteen lesion patterns identified by factor analysis were studied in relation to the clinical features. Severe maternal proteinuria was related to placental chronic inflammation, while lower maternal antepartum platelet counts were related to placental abruption and infarct. Lower birthweight percentile and lighter placentae were related directly to uteroplacental vascular lesions. Diagnosis of HELLP and coagulopathy were less common when chronic inflammation scores were high. Serologic studies related to autoimmunity and maternal blood pressures were unrelated to placental histopathology factors. It is concluded that features of maternal and fetal compromise in preterm pre-eclampsia are related to placental histopathology patterns.

Clinical correlations of patterns of placental pathology in preterm pre-eclampsia

The objective of this study was to determine if placental histopathology patterns are associated with clinical features of preterm pre-eclampsia. A 1989–1993 database of consecutive non-anomalous singleton livebirths delivered at 22–32 weeks gestation excluding cases of maternal diabetes mellitus and chronic hypertension included 74 cases of pre-eclampsia. Placentae were scored for uteroplacental vascular lesions and lesions of chronic inflammation and coagulation. Thirteen lesion patterns identified by factor analysis were studied in relation to the clinical features. Severe maternal proteinuria was related to placental chronic inflammation, while lower maternal antepartum platelet counts were related to placental abruption and infarct. Lower birthweight percentile and lighter placentae were related directly to uteroplacental vascular lesions. Diagnosis of HELLP and coagulopathy were less common when chronic inflammation scores were high. Serologic studies related to autoimmunity and maternal blood pressures were unrelated to placental histopathology factors. It is concluded that features of maternal and fetal compromise in preterm pre-eclampsia are related to placental histopathology patterns.

Gastric mucosal secretion of interleukin-10: relations to histopathology, Helicobacter pylori status, and tumour necrosis factor-alpha secretion.

Interleukin-10 (IL-10) is an 18 kDa peptide with a range of anti-inflammatory and immunosuppressive properties. To determine whether this cytokine is involved in gastric mucosal inflammation in Helicobacter pylori infection. The production of IL-10 by antral mucosal biopsy specimens during short term in vitro culture was determined by measuring IL-10 content of supernatants by enzyme linked immunosorbent assay (ELISA). H pylori status was determined by serology and histology, with gastritis scored using the Sydney system. Tumour necrosis factor-alpha (TNF-alpha) content of supernatants was also determined in a subgroup of patients. IL-10 secretion was significantly greater in patients with H pylori associated chronic gastritis than in patients who were H pylori negative with normal mucosa/reactive changes, and those with H pylori negative chronic gastritis (p < 0.01 and < 0.05 respectively). There was a significant correlation overall between IL-10 secretion and chronic inflammation score (r = 0.40). Secretion of TNF-alpha, which was significantly higher in H pylori infected patients than uninfected patients with a normal mucosa (p < 0.04), correlated with scores for chronic inflammation and activity (r = 0.39 and 0.38 respectively), but was only weakly correlated with IL-10 secretion (r = 0.22, NS). Gastric mucosal production of IL-10 and TNF-alpha are increased in chronic gastritis associated with H pylori infection, and mucosal cytokine secretion varies with important histopathological aspects of gastric inflammation. Whereas the secretion of IL-10 in H pylori infection may be protective, limiting tissue damage caused by inflammation, it may also contribute towards failure of the immune response to eliminate the organism.

Implications of Helicobacter pylori serological titer for the histological severity of antral gastritis.

We attempted to determine whether the serological titer of anti-Helicobacter pylori (HP) immunoglobulin (IgG) would be capable of predicting the presence of ulcer, or would correlate with the histological grading of gastritis in patients with dyspepsia. One hundred eighty-three dyspeptic patients were prospectively included in the study after panendoscopy. Each patient underwent blood sampling for anti-HP IgG titer, and antral biopsy for both a rapid urease test (CLO) and histology. The severity of antral gastritis was semi-quantitated for acute and chronic inflammation scores (range 0-3). The HP findings were positive in 157 patients (85.5%), and their histological inflammation scores and serological titer were higher than those of HP-negative patients (P < 0.05). Based on the endoscopic findings, these 157 patients were classified into ulcer (n = 109) and non-ulcer dyspepsia (n = 48) subgroups. The mean chronic inflammation score in the ulcer subgroup was higher than that in the non-ulcer dyspepsia subgroup (1.77 vs. 1.28, P < 0.001). However, on the basis of only the titer itself, there was no cut-off value for serological titer to predict the presence or absence of ulcer in HP-infected patients. As the scores for either acute or chronic inflammation increased, the mean serological titer rose (acute inflammation score 0-3: 0.63, 0.78, 0.93, 1.39; chronic inflammation score 0-3: 0.18, 0.56, 0.88, 0.91). The titer of HP serology does not provide a method for predicting the presence of ulcer in patients with HP infection, but may indirectly offer evidence of the severity of histological changes.

Gastric inflammation and neutrophil-activating and cytotoxin-producing Helicobacter pylori strains.

Some Helicobacter pylori strains activate human neutrophils without opsonins and/or produce vacuolating cytotoxin. Human gastric isolates of H. pylori were studied for their ability to nonopsonized induce an oxidative burst in human neutrophils as measured by chemiluminescence and for the production of vacuolating cytotoxin. In all, 80 strains were examined, and the type and grade of inflammation in the gastric biopsy specimens from the antrum and corpus of these patients were assessed in accordance with the Sydney system. CL+ (rapid, strong response in chemiluminescence) strains (p < 0.0001) and Tox+ (cytotoxin-producing) strains (p < 0.0001) were associated with higher acute inflammation scores in gastric ulcer patients. CL+ (p = 0.0002) and Tox+ (p < 0.0001) strains were also associated with higher chronic inflammation scores in gastric ulcer patients. CL+ and Tox+ strains seem to cause more severe inflammation in the gastric mucosa during H. pylori infection.

Effects of the faecal stream and stasis on the ileal pouch mucosa.

This study aimed to investigate the effects of the faecal stream and stasis on the mucosa of ileal pouches. Nine patients were followed up. Two pouch biopsy specimens were obtained from each at the time of pouch formation, ileostomy closure, and three, six, and 12 months after operation. None developed pouchitis. Two pouch biopsy specimens each were also obtained from 20 patients (six with pouchitis), whose pouches had been functioning for at least a year and in whom pouch evacuation was assessed by radioisotope labelled artificial stool. Biopsy specimens were assessed for the degree of acute and chronic inflammation, mucin type (high iron diamine-alcian blue stain), a morphometric index of villous atrophy (villous height:total mucosal thickness), and crypt cell proliferation (using the monoclonal antibody Ki67). Mean values from the two biopsy specimens were obtained for each parameter. After three months of pouch function, the scores for acute and chronic inflammation, the degree of sulphomucin, and crypt cell proliferation were significantly higher, and the index of villous atrophy was significantly lower (indicating a greater degree of villous atrophy), than at pouch formation or at ileostomy closure. The values at pouch formation and ileostomy closure were similar. For all parameters, the changes seen at six and 12 months were not significantly different from those at three months. There was no significant correlation between the efficiency of pouch evacuation and any of the mucosal changes. It is concluded that exposure to the faecal stream is necessary for changes to take place in the pouch mucosa, although the amount of stasis, as measured by radioisotopic evacuation studies, seems to be irrelevant. The mucosal changes occur soon after ileostomy closure and then remain stable for at least one year.

Campylobacter pylori and Barrett's Esophagus

Campylobacter pylori is thought to be confined to gastric mucosa; when detected in the duodenum in association with duodenal ulceration, the organism infects only areas of gastric metaplasia. Barrett's esophagus is a metaplastic condition of the esophagus, in which areas or islands of "gastric-type" epithelium are found. To determine whether C. pylori colonized the esophagus of patients with Barrett's esophagus, we studied retrospectively 23 unselected patients who had endoscopic and biopsy evidence of Barrett's esophagus. Mucosal biopsy specimens were stained by the Warthin-Starry silver technique and reviewed by an experienced, "blinded" histopathologist. Of the 23 patients, 12 (52%) had C. pylori in the esophagus. Patients with and those without C. pylori were of similar age and gender, had similar scores for acute and chronic inflammation, and had similar lengths of tubular esophagus with metaplastic gastric mucosa. These observations suggest that C. pylori commonly infects Barrett's esophagus. The clinical importance of this finding is unknown.