Reflux gastritis in the intact stomach.

Gastric biopsy specimens from patients who have undergone gastric surgery frequently exhibit foveolar hyperplasia, oedema, vasodilatation and congestion, and a paucity of inflammatory cells as consequences of entero-gastric reflux. Similar, albeit generally milder, changes were found in 47 of 316 (15%) non-surgical patients undergoing endoscopy for dyspeptic symptoms. To relate these changes to bile reflux or other potential gastric irritants the total bile acid concentration was measured in samples of fasting gastric juice, and the use of a symptom questionnaire ascertained the patients' cigarette consumption, use of non-steroidal anti-inflammatory drugs (NSAIDs), and alcohol intake. When patients with reflux gastritis were compared with normal controls (n = 91), significant increases in associated peptic ulceration and NSAID use were found in the group with reflux, but no increases in bile acid concentrations. Indeed, only one patient had evidence of duodenogastric reflux. It is concluded that most cases of "reflux gastritis" in the intact stomach are not due to reflux of bile. Our findings indicate an important pathogenic role for long term NSAID use, in what might be usefully termed type C or "chemical" gastritis.     

Cell proliferation in the post-surgical stomach, dietary salt, and the effect of H pylori eradication

AIMS: To study the epithelial kinetics of the post-surgical stomach with reference to dietary salt intake and H pylori. METHODS: Endoscopic biopsies of the antrum/anastomosis and corpus were taken for histology and MIB-1 immunostaining. The labelling index (LI%) was determined in the three zones of the gastric glands (zone 1 = surface + gastric pit; zone 2 = isthmus; zone 3 = gland base) in patients with vagotomy and pyloroplasty (n = 12), gastroenterostomy + vagotomy (n = 4), partial gastrectomy (n = 3), and Billroth I operation (n = 3). Dietary salt was determined by urinary sodium/creatinine ratio. Twelve patients were H pylori positive (10 vagotomy and pyloroplasty; 2 partial gastrectomy) and had a repeat biopsy three months after antihelicobacter treatment (10 were H pylori negative after treatment). RESULTS: There was no correlation between salt intake and antrum/anastomosis (r = -0.34; p = 0.2) or corpus (r = -0.16; p = 0.2) labelling indices. Gastric mucosal proliferation is increased in the antrum/ anastomosis compared to the corpus in H pylori positive (p = 0.014) but not H pylori negative subjects (p = 0.084). This may reflect the different types of post-surgical stomach in each group. Gastric mucosal proliferation is reduced in antrum/anastomosis (p = 0.002) and corpus (p = 0.016) following H pylori eradication. CONCLUSIONS: Dietary salt does not influence gastric mucosal proliferation in the post-surgical stomach but H pylori may have a role in gastric stump carcinogenesis.     

Increase in proliferation and apoptosis of gastric epithelial cells early in the natural history of Helicobacter pylori infection.

Childhood acquisition of Helicobacter pylori is a critical risk factor for gastric cancer. Since tumorigenesis involves deregulation of proliferation and apoptosis, we examined gastric epithelial cell proliferation and apoptosis in H. pylori-infected children. Apoptosis and proliferation of gastric antral epithelial cells in biopsy specimens from patients with H. pylori-induced gastritis, secondary gastritis, and noninflamed controls were compared. p53 protein expression was examined immunohistochemically. Apoptotic cells were identified in the surface epithelium in each group. The apoptotic index was higher in specimens from patients with H. pylori gastritis (120 +/- 10) than secondary gastritis (50 +/- 10) and noninflamed controls (40 +/- 10, analysis of variance P < 0.005). Apoptosis decreased following H. pylori eradication and resolution of gastritis (P < 0.02). An expanded proliferative compartment was identified in H. pylori-induced gastritis (32.4 +/- 3.5; proliferative labeling index +/- SE) compared with secondary gastritis (18.9 +/- 2.8) and noninflamed controls (13.7 +/- 3.1, analysis of variance P < 0.01). The accelerated cell turnover was associated with p53 overexpression (analysis of variance P < 0.005). Accumulation of p53 was not associated with expression of the cyclin-dependent kinase inhibitor p21. The occurrence of altered cell turnover early in the natural history of chronic infection provides an explanation for the increased risk of gastric cancer development associated with childhood acquisition of infection.     

Cell proliferation in normal and diseased gastric mucosa. Autoradiography after in vitro continuous labelling with tritiated thymidine.

The rate of gastric epithelial cell proliferation was studied in healthy volunteers and in patients with different degrees of gastritis. Endoscopic biopsies from the antral and fundic part of the stomach were incubated in vitro with 3H-thymidine for 30, 120, and 210 minutes respectively. Autoradiographs were prepared, and the percentage of DNA-synthesizing cells (labeling index) in the progenitor cell region was estimated. From the successive labeling indices the rate of entry of cells into DNA-synthetic phase (S-phase) and the duration of the S-phase could be estimated. All the biopsies were classified according to the degree of gastritis. The mean (+/-SEM) length of the S-phase was found to be 7.4 +/- 0.3 hours in antral mucosa and 7.2 +/- 0.4 hours in fundic mucosa. There was no significant difference between the S-phase duration in normal mucosa, superficial gastritis, mild atrophic gastritis and severe atrophic gastritis. This observation suggests that the labeling index can be used as an expression for the rate of cell proliferation in human gastric mucosa. A significant correlation between the labelling indices and the degree of gastritis was found in both antral and fundic mucosa. In six cases, labelling indices estimated by cell counts performed on longitudinal or cross sections of foveolae were compared. Ther was no significant difference between the results obtained by the two different counting techniques.     

Bile reflux and intestinal metaplasia in gastric mucosa.

AIM: To determine associations between enterogastric bile reflux and gastric mucosal pathology. METHOD: A retrospective study using fasting gastric juice bile acid measurements and antral or prestomal biopsy specimens from 350 patients, 66 of whom had previously undergone surgery that either bypassed or disrupted the pyloric sphincter. RESULTS: Bile reflux was positively associated with reactive gastritis and negatively with Helicobacter pylori density. After stratification for previous surgery, age, and H pylori status, the histological feature most strongly associated with bile reflux was intestinal metaplasia, including all its subtypes. The prevalence of intestinal metaplasia was greatest in patients with both H pylori infection and high bile acid concentrations. Bile reflux was also positively associated with the severity of glandular atrophy, chronic inflammation, lamina propria oedema and foveolar hyperplasia. CONCLUSIONS: Bile reflux is a cause of reactive gastritis. It modifies the features of H pylori associated chronic gastritis. The changes are not confined to patients who have had surgery to their stomachs. The positive associations with atrophy and intestinal metaplasia have implications for models of gastric carcinogenesis.     

Gastric mucosal inflammation and epithelial cell turnover are associated with gastric cancer in patients with Helicobacter pylori infection

BACKGROUND: Infection with a virulent Helicobacter pylori strain is associated with gastric mucosal damage and the increased risk of gastric cancer. AIMS: To examine the characteristics of host gastric mucosal responses in patients with gastric cancer, histological grade of gastritis, gastric epithelial apoptosis, and proliferation were studied. METHODS: Thirty two patients with early gastric cancer and 32 sex and age matched controls were studied. All subjects were infected with a virulent H pylori strain (vacA s1/m1, cagA positive genotype). Biopsy specimens were taken from the antrum and the corpus of the stomach. The grade of gastritis was assessed according to the updated Sydney system. Apoptotic cells were detected using terminal uridine deoxynucleotidyl nick end labelling, and epithelial cell proliferation was determined by means of the Ki-67 labelling index. RESULTS: In patients with gastric cancer, significantly higher grades were observed when glandular atrophy (p < 0.05) and intestinal metaplasia (p < 0.01) were present in the antrum, and when mononuclear cell infiltration was present in the corpus (p < 0.05). The numbers of apoptotic cells were increased in patients with cancer (p < 0.05) and the apoptotic index correlated significantly with the grade of glandular atrophy. Epithelial cell proliferation was more likely to be increased in mucosa where intestinal metaplasia was present. CONCLUSIONS: Infection with H pylori causes increased gastric epithelial apoptosis, resulting in more severe glandular atrophy in patients with gastric cancer. Increased damage of gastric epithelial DNA and the presence of more severe atrophic gastritis might contribute to the development of gastric cancer.     

Campylobacter like organisms and reflux gastritis.

A total of 98 patients, who had undergone gastric surgery (23), or who had peptic ulcers (56), or who had normal endoscopic findings (19) underwent gastric biopsy, together with measurement of pH and total bile acid concentration, in their fasting gastric juice. The biopsy specimens were stained by the Warthin-Starry method for Campylobacter like organisms and were also graded "blind," as described in the preceding paper, for the five features that we believe may constitute the histological picture of reflux gastritis. The individual grades were added together to give a composite "reflux score" (0-15) for each patient. We found a notable association between the absence of Campylobacter like organisms and previous surgery for peptic ulceration, high reflux scores (greater than 10), hypochlorhydria (pH greater than or equal to 4), and increased bile acid concentrations (greater than or equal to 1 mmol/l) in the stomach. These findings further support our contention that reflux gastritis represents a distinct histopathological entity causally related to the effects of enterogastric reflux on the gastric mucosa and suggest that there may be two major categories of chronic gastritis: chronic superficial, or atrophic gastritis related to Campylobacter like organisms and reflux gastritis. Our data also imply that patients with peptic ulceration may, after gastric surgery, revert from being positive for these organisms to being negative and may undergo a possible transition from Campylobacter related chronic gastritis to reflux gastritis.     

Histologic and endoscopic studies before and after gastric bypass surgery

The purposes of this study were to establish a standardized multiparameter analysis system for histologic grading of gastritis and to compare histologic changes with endoscopic findings in the proximal and distal bypassed stomach in obese patients undergoing gastric bypass surgery. Three groups, comprising a total of 91 patients, were studied: a preoperative group (34 patients), a postoperative group at one year (33 patients), and a postoperative group at two years (24 patients). the biopsy specimens from the proximal and distal bypassed stomach were compared in all groups. Seventeen histologic variables were evaluated by three observers to classify the severity of gastritis. Forty percent of the patients in the postoperative group demonstrated histologic evidence of nonerosive, superficial gastritis, slightly more in the proximal stomach. Endoscopy showed significantly more bile reflux and inflammation in the distal stomach than the proximal stomach in nearly all patients. Our study demonstrates a significant discrepancy between bile reflux observed endoscopically and the histologic findings after gastric bypass surgery. No metaplastic or dysplastic changes were found up to two years postoperatively, but further studies are needed to determine the long-term endoscopic and histologic endoscopic and histologic sequelae of gastric bypass surgery.     

Mucosal mast cells in reflux gastritis and chronic (type B) gastritis

The histological features that characterize alkaline reflux gastritis are typical of the histamine-mediated response to tissue injury. We have investigated this in nine patients with symptomatic reflux gastritis following partial gastrectomy for duodenal ulcer by determining the gastric mucosal mast cell count before and after Roux-en-Y biliary diversion. Following diversion, the histological picture changed from that of reflux gastritis to type B chronic gastritis in all cases. The mean mucosal mast cell count in all patients was 47.57/mm2 before diversion and 123.33/mm2 after diversion (P less than 0.05). Analysis of the paired data, in which eight out of nine patients showed a rise in mucosal mast cell numbers following bile diversion, also showed a significant difference before and after surgery (P less than 0.01). The gastric mucosal mast cell count is significantly less in reflux gastritis than in type B chronic gastritis. This is most likely to be due to increased degranulation, which would explain why striking vascular changes occur in the absence of inflammatory cell infiltration in reflux gastritis.     

ABO (H) blood group antigen expression in gastric mucosa

The A, B, O (H) blood group antigens (BGA) are glycolipids present in the plasma membranes of many different epithelial cells. Alterations in BGA expression have been described in malignant tumors and premalignant lesions. We have studied ABO (H) BGA expression in paraffin sections of gastric specimens using immunofluorescence techniques with monoclonal antibodies. 102 patients were studied. 15 with normal mucosa (NM); 16 with duodenal ulcer (DU); 23 with gastric ulcer (GU); 11 with pernicious anaemia (PA) and 37 with adenocarcinoma (AC). The expression of BGA in normal gastric mucosa is detected in surface epithelium, mucoid cell neck glands and parietal cells as well as 2/3 of antral glands. BGA expression in DU gastritis is very similar to that seen in NM. In atrophic chronic gastritis associated with GU and PA there is a significant decrease in BGA expression. In patients with PA, BGA expression is greater in antral mucosa than in fundic mucosa. Loss of BGA expression is more pronounced in atrophic chronic gastritis surrounding AC. Intestinal metaplasia shows variable BGA expression. Our results support the hypothesis that loss of BGA expression by epithelial gastric mucosal cells may be related to alterations in cellular differentiation and premalignant potential.     

Cell density of adrenomedullin-immunoreactive cells in the gastric endocrine cells decreases in antral atrophic gastritis

AIMS: Adrenomedullin (AM) is a novel hypotensive and vasorelaxing peptide recently isolated from human phaeochromocytoma tissue, and is widely distributed in various organs. In this study we examined the localization of AM-immunoreactive (IR) cells in the gastric mucosa and AM-IR cell density in antral atrophic gastritis. METHODS AND RESULTS: Gastric mucosal tissues were taken from the gastric body and antral mucosa of 52 patients (27 men, 25 women; mean age 56.0 (range 20-86) years). Immunohistochemical analysis revealed that AM-IR cells were present in the pyloric glands, but not in the fundic glands, and that AM-IR cells were stained positively for chromogranin A and gastrin. The percentage of AM-IR cells vs chromogranin A- and gastrin-IR cells was 42 and 56%, respectively. The number of AM-IR cells decreased with the progression of severity of atrophic changes in the pyloric gland, and also of mononuclear cell infiltration. There was no correlation between the number of AM-IR cells and the degree of neutrophilic infiltration. Similar findings were also obtained for gastrin-IR cells. CONCLUSION: AM-IR cells are present in the endocrine cells including gastrin-IR cells in the pyloric glands. These results suggest that AM may contribute to gastrin secretion in the pyloric glands.     

Correlation between epithelial cell proliferation and histological grading in gastric mucosa

AIM: To determine if there is a correlation between the histological findings in the gastric mucosa and the degree of cell proliferation in gastric antral biopsies. METHODS: Cell proliferation in gastric antral biopsies was determined by in vitro bromodeoxyuridine labelling. Histological sections were assessed using the Sydney System. RESULTS: There was a positive correlation between antral mucosal cell proliferation and the acute inflammatory cell infiltrate (r = 0.29; p = 0.03). There was a stronger correlation with the chronic inflammatory cell infiltrate (r = 0.53; p < 0.0001) and the density of H pylori colonisation (r = 0.54; p < 0.0001). There was no correlation between gastric epithelial proliferation and the degree of atrophy. Stepwise multiple regression indicates that the only independent predictor of epithelial cell proliferation is the density of H pylori colonisation (p < 0.0001). CONCLUSIONS: H pylori increases gastric epithelial cell proliferation through the mucosal inflammatory response and probably by other means. The strong correlation between epithelial proliferation, the chronic inflammatory cell infiltrate, and the density of H pylori colonization may have implications for gastric carcinogenesis.     

Identification of Paneth cells in pyloric glands associated with gastric and intestinal mixed-type intestinal metaplasia of the human stomach

We have proposed that intestinal metaplasia (IM) of the human stomach be divided into two types on the basis of cell differentiation status: a gastric and intestinal (GI) mixed type and a solely intestinal (I) type. In the GI mixed type, gastric (foveolar epithelial and pyloric gland cells) and intestinal (goblet, intestinal absorptive, and Paneth cells) phenotype cells coexist in the same intestinalized gastric glands in various combinations and degrees. Consequently, intestinalized gastric glands are hybrids. Although we have described the rare appearance of Paneth-like cells in pyloric glands of GI mixed-type IM, the absence of an appropriate Paneth cell marker leaves room for doubt as to their true character. The purpose of this study was to clearly identify Paneth cells in pyloric glands in IM lesions using a new Paneth cell marker, a polyclonal antibody human defensin (HD)-5, raised against HD-5, which is included in granules of Paneth cells. A total of 105 gastric samples (4 biopsy and 101 surgical resected specimens) were examined. In only nine cases (8.6%), the antibody allowed demonstration of Paneth cells in pyloric glands in GI mixed-type IM, confirming our previous finding. Analysis of the proliferative cell (P) zone indicated that a common stem cell might generate both GI phenotype cells by upward and downward migration. No Paneth cells were found above the P zone. The results suggest that the stem cells show abnormal cell differentiation in IM lesions but preserve their normal direction of migration.     

The effect of gender on Helicobacter felis-mediated gastritis, epithelial cell proliferation, and apoptosis in the mouse model

The murine Helicobacter felis model has been extensively used to investigate the importance of host factors in the development of chronic gastritis. The effect of gender in this murine model is unknown. Male and female C57BL/6J mice were infected with H felis for up to 1 year. At 4, 8, 19, 36, and 52 weeks post-infection, gastric histopathology, epithelial cell proliferation, and apoptosis were examined and compared with age- and gender-matched controls. In female mice, infection with H felis resulted in an earlier onset of chronic gastric inflammation, epithelial hyperplasia, and oxyntic cell loss than males. In females, there was a trend towards increased gastric pathology compared with males, with long-term-infected female mice having significantly greater (p < 0.05) chronic inflammation than male mice. The histopathological differences in male and female mice did not relate to the density of H felis infection. Female mice infected with H felis had significantly increased gastric epithelial cell proliferation in the cardia and corpus at both 8 and 52 weeks post-infection (p < 0.05). Epithelial cell apoptosis in the glandular mucosa of the corpus at 36 and 52 weeks post-infection was significantly increased (p < 0.05) in female mice compared with uninfected gender controls. In contrast, there was no significant increase in epithelial cell proliferation or apoptosis in any area of the stomach at any time point after H felis infection in male mice. These results demonstrate that there are gender differences in the gastric inflammatory and epithelial response to H felis in the murine model. The functional importance of gender should be considered in future murine studies on H felis- and H pylori-induced chronic gastritis.     

胃超高分化腺癌12例临床病理学特征分析

目的探讨胃超高分化腺癌(very well differentiated adenocarcinoma,VWDA)的临床病理学特征。方法收集2013年1月至2021年5月解放军联勤保障部队第九八九医院平顶山医疗区(原第一五二中心医院)诊断的胃VWDA 12例,收集患者的临床病理资料,观察其组织形态学特征和免疫表型,并结合文献进行分析。结果12例患者中男8例,女4例,中位年龄63岁(范围47~80岁)。胃上部6例,胃中部2例,胃下部4例。肿瘤中位直径17 mm(范围5~65 mm)。构成肿瘤的细胞类似吸收细胞、Paneth细胞、小凹上皮细胞和杯状细胞。细胞单层排列,核轻度增大位于基底侧,核呈纺锤形至轻度不规则形,核极向紊乱。早期胃管状VWDA 9例,肿瘤腺管类似肠上皮化生的腺管,其中2例浸润至黏膜下层,黏膜深部及黏膜下层的病变表现为腺管囊性扩张、弯曲、分支、尖角,以及流产型腺管。早期胃乳头状管状VWDA 1例,癌局限于黏膜层内,由小凹型上皮细胞构成。胃进展期乳头状管状VWDA 2例,由小凹型上皮、幽门腺或颈黏液细胞构成,且伴有淋巴管内癌栓和淋巴结转移。所有病例背景黏膜均见萎缩和肠上皮化生。免疫组织化学染色显示肠型1例,胃肠混合型9例,胃型2例。仅局限于黏膜内的8例胃VWDA Ki-67阳性指数40%~70%,2例浸润到黏膜下层的癌和2例进展期癌Ki-67阳性指数10%~25%。所有肿瘤均显示p53蛋白呈野生型表达模式、HER2阴性。在术前活检中被诊断为腺癌或高级别异型增生5例、慢性萎缩性胃炎伴肠上皮化生7例。术后中位随访时间28个月(范围12~72个月),10例早期癌未见复发;2例进展期癌中1例发生肺转移,另1例死亡。结论胃VWDA是罕见的低度恶性肿瘤,具有高分化腺癌的结构特征和极低度的细胞学异型性。结构异型性的诊断价值显著大于细胞学异型性,黏膜深部和黏膜下层的不规则腺管浸润性生长是诊断的可靠依据。黏膜内VWDA诊断具有挑战性,活检标本中的部分病例难以明确诊断。     

Possible association of active gastritis, featuring accelerated cell turnover and p53 overexpression, with cancer development at anastomoses after gastrojejunostomy. Comparison with gastroduodenostomy

To cast light on tumorigenesis in the remnant stomach after distal gastrectomy for peptic ulcer or gastric cancer, 45 cases in gastroduodenostomy (Billroth I, 17 cases) and gastrojejunostomy (Billroth II, 28 cases) groups were compared for a series of parameters. Cancers in Billroth II were significantly more predominant in the anastomosis area and more frequently associated with Epstein-Barr virus infection. Active gastritis, accelerated epithelial cell turnover (as assessed by measurements of apoptosis and cell proliferation), DNA damage, and foveolar cell hyperplasia were all greater in anastomotic areas after Billroth II than in proximal areas after Billroth II or either area after Billroth I. K-ras mutations were rare, but Epstein-Barr virus infection in cancers was seen frequently in anastomosis cases. In conclusion, active gastritis, possibly induced by enterogastric reflux, is linked to tumorigenesis in anastomosis sites in Billroth II cases.     

Alterations in the proliferating compartment of gastric mucosa during Helicobacter pylori infection: the putative role of epithelial cells expressing p27(kip1).

The proliferating zone contains stem cells that give rise to all epithelial cells of the gastric mucosa. In the present study, we investigated the turnover of gastric epithelial cells in the proliferating zone of Helicobacter pylori-infected mucosa, with or without intestinal metaplasia, before and after eradication of the microorganism. In addition, we studied the topographical distribution of the cyclin dependent kinase inhibitor p27(Kip1), which plays a critical role in cell cycle progression and differentiation programs. Twenty-eight patients (22 male), aged 32-78 years and with dyspeptic symptoms, were endoscoped, and gastric biopsies were obtained from antrum and corpus for histopathological examination and the Campylobacter-like organisms test; eradication therapy was given to infected patients, and all patients were re-endoscoped after 105 +/- 33 days (mean +/- SD). The kinetics of gastric epithelial cells and p27(Kip1) status was assessed by means of immunohistochemistry and TUNEL (Tdt-mediated dUTP-biotin nick end labeling) assay. Twenty-one (21) of 28 patients were H. pylori positive, and 7 were found H. pylori negative and served as controls. In antrum, intestinal metaplasia was detected in 7/21 (33.3%). In H. pylori gastritis, Ki67 expression was found increased in the proliferating zone, compared with normal (P =.03); analogous results were obtained with the other proliferation markers, namely retinoblastoma protein and topoisomerase IIalpha. An inverse relationship between proliferation index and atrophy was disclosed (P =.02). A reduction in the proliferation index was observed after eradication, albeit not significant. Apoptotic epithelial cells were found significantly increased (P <.01) in H. pylori gastritis, and a significant reduction was observed after eradication (P <.01). In addition, apoptotic index was found to correlate with H. pylori density. The topographical study of p27(Kip1) revealed a p27(kip1)-positive epithelial cell population that resided deep in the proliferating zone; these cells were considered to be stem cells and were found significantly increased in areas with intestinal metaplasia (P <.05); in H. pylori gastritis, there was also an increase that did not reach statistical significance. H. pylori infection induces apoptosis and increases proliferation in the proliferating zone. The increased cellular turnover, together with the increased number of putative p27(Kip1)-positive stem cells in the context of intestinal metaplasia, provides further evidence for the role of H. pylori infection in gastric carcinogenesis.     

Augmented gp130-mediated cytokine signalling accompanies human gastric cancer progression

H. pylori infection accounts for most cases of gastric cancer, but the initiating events remain unclear. The principal H. pylori pathogenicity-associated CagA protein disrupts intracellular SHP-2 signalling pathways including those used by the IL-6 family cytokines, IL-6 and IL-11. Imbalanced IL-6 family cytokine signalling in the gp130(757FF) mouse model of gastric cancer arising from hyperactivation of oncogenic STAT3 after altered SHP-2 : ERK1/2 signalling produces dysplastic antral tumours preceded by gastritis and metaplasia. In a cohort of patient gastric biopsies with known H. pylori and CagA status, we investigated whether (i) STAT3 and ERK1/2 activation is altered in H. pylori-dependent gastritis; (ii) these profiles are more pronounced in CagA+ H. pylori infection; and (iii) the expression of pro-inflammatory cytokines that activate STAT3 and ERK 1/2 pathways is associated with progression to gastric cancer. IL-6, IL-11, and activated STAT3 and ERK1/2 were quantified in antral biopsies from gastritic stomach, metaplastic tissue, and resected gastric cancer tissues. We observed significantly increased STAT3 and ERK1/2 activation (p = 0.001) in H. pylori-dependent gastritis, which was further enhanced in the presence of CagA+ H. pylori strains. Of known gastric ligands that drive STAT3 activation, IL-6 expression was increased after H. pylori infection and both IL-6 and IL-11 were strongly up-regulated in the gastric cancer biopsies. This suggests a mechanism by which IL-11 drives STAT3 activation and proliferation during gastric cancer progression. We addressed this using an in vitro approach, demonstrating that recombinant human IL-11 activates STAT3 and concomitantly increases proliferation of MKN28 gastric epithelial cells. In summary, we show increased STAT3 and ERK1/2 activation in H. pylori-dependent gastritis that is likely driven in an IL-6-dependent fashion. IL-11 expression is associated with adenocarcinoma development, but not gastritic lesions, and we identify a novel mechanism for IL-11 as a potent inducer of proliferation in the human gastric cancer setting.     

Atrophic gastritis: Structural and ultrastructural alterations,exfoliative cytology and enzyme cytochemistry and histochemistry,proliferation kinetics,immunological derangements and other causes,and clinical associations and sequellae

Our main purpose in this review article is to present some of the vast amount of information on the subject of atrophic gastritis available at the present time. Various areas of research pertaining to this entity, including that from the author's laboratory, are reviewed in this article, encompassing histological and ultrastructural abnormalities, enzyme histochemistry, and exfoliative cytology and cytochemistry of chronic gastritis, with emphasis on the diagnostic significance of these laboratory methods. The altered cell proliferation kinetics in atrophic gastric lesions is also discussed, as well as its significance in the proliferation and reduction of glandular cells of the gastric mucosa. Furthermore, some of the more recent evidence of immunological mechanisms and other causes of chronic gastritis, such as chronic alcoholism and bile reflux, is reviewed, as well as the effects of partial gastrectomy on the gastric mucosa. The important associations and sequellae of atrophic gastritis, such as gastric ulcer, gastric polyps, and gastric cancer, are discussed in detail.     

Reflux gastritis: distinct histopathological entity?

A total of 98 patients who had either undergone gastric surgery (23) or who had peptic ulcers (56), or who had normal endoscopic findings (19), all underwent gastric biopsy, together with measurement of pH and total bile acid concentration in their fasting gastric juice. The biopsy specimens were graded "blind" for the presence of foveolar hyperplasia; oedema and smooth muscle fibres in the lamina propria; vasodilation and congestion of superficial mucosal capillaries; and a paucity of both acute and chronic inflammatory cells in the brief that these features constituted a distinctive histological picture related to reflux of alkaline duodenal content into the stomach. We found a strong association between severe grades of each of these histological variables and both hypochlorhydria (pH greater than or equal to 4) and increased bile acid concentrations in the stomach. Furthermore, when the individual grades were added together to give a composite "reflux score," there was a significant difference in the incidence of hypochlorhydria (p less than 0.01) and raised bile acid concentrations (p less than 0.005) between those patients with a reflux score above and below 10. Although we do not claim that reflux is invariably accompanied by a distinctive histological picture, we suggest that recognition of this hitherto poorly documented combination of features as reflux gastritis may assist in the selection of patients for specific treatment and minimise the overdiagnosis of premalignant dysplasia (with which the lesion may be confused) in the postoperative stomach.