CagA+ Helicobacter pylori infection and gastric cancer risk in the EPIC-EURGAST study

Helicobacter pylori (H. pylori), atrophic gastritis, dietary and life-style factors have been associated with gastric cancer (GC). These factors have been evaluated in a large case-control study nested in the European Prospective Investigation into Cancer and Nutrition carried out in 9 countries, including the Mediterranean area. Participants, enrolled in 1992-1998, provided life-style and dietary information and a blood sample (360,000; mean follow-up: 6.1 years). For 233 GC cases diagnosed after enrolment and their 910 controls individually-matched by center, gender, age and blood donation date H. pylori antibodies (antilysate and antiCagA) and plasma Pepsinogen A (PGA) were measured by ELISA methods. Severe chronic atrophic gastritis (SCAG) was defined as PGA circulating levels <22 microg/l. Overall, in a conditional logistic regression analysis adjusted for education, smoke, weight and consumption of total vegetables, fruit, red and preserved meat, H. pylori seropositivity was associated with GC risk. Subjects showing only antibodies anti-H. pylori lysate, however, were not at increased risk, while those with antiCagA antibodies had a 3.4-fold increased risk. Overall, the odds ratio associated with SCAG was 3.3 (95% CI 2.2-5.2). According to site, the risk of noncardia GC associated with CagA seropositivity showed a further increase (OR 6.5; 95% CI 3.3-12.6); on the other hand, a ten-fold increased risk of cardia GC was associated with SCAG (OR 11.0; 95% CI 3.0-40.9). These results support the causal relationship between H. pylori CagA+ strains infection, and GC in these European populations even after taking into account dietary habits. This association was limited to distal GC, while serologically defined SCAG was strongly associated with cardia GC, thus suggesting a divergent risk pattern for these 2 sites.     

Control of pepsinogen synthesis and secretion in primary monolayer cultures of canine gastric chief cells

We have studied pepsinogen synthesis and secretion in primary monolayer cultures of canine gastric chief cells. Monolayers were formed after approximately 48 hr. Pepsinogen synthesis was studied by adding¹⁴C-labeled amino acids to the culture medium. Basal secretion of de novo synthesized pepsinogen after 4 hr was 4±1.2% of total newly synthesized pepsinogen. Basal secretion of stored pepsinogen after 90 min was 8±1.4% of total pepsinogen content. Carbachol, dbcAMP, forskolin, VIP, CCK-8, and the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate all stimulated secretion of de novo synthesized pepsinogen and preformed pepsinogen. Only additive interactions were found. dbcAMP caused a peak outburst of stored pepsinogen in the first 10 min. Carbachol stimulation was time dependent. Stimulation of de novo synthesized pepsinogen secretion was time dependent for both carbachol and dbcAMP. dbcAMP caused an immediate 10-fold increase in pepsinogen synthesis, but carbachol did so only after a lag time of 30 min. This was identical to the time necessary for the appearance of labeled pepsinogen in the medium. Addition of atropine after 2 hr resulted in a return to basal synthesis. Stimulated pepsinogen synthesis was always observed concomitant with stimulated pepsinogen secretion. These results show that most external stimuli for pepsinogen synthesis are dependent upon prior depletion of pepsinogen stores, which then triggers synthesis, while stimulation of cAMP production stimulates pepsinogen synthesis more directly.     

Influence of endoscopic submucosal dissection on serum levels of pepsinogens in patients with early gastric cancer

Background: The serum levels of pepsinogens (PG) have been considered to be a useful marker for assessing the risk of metachronous gastric cancer in patients who undergo endoscopic submucosal dissection. However, the influence of endoscopic submucosal dissection (ESD) on serum levels of PG has not yet been examined. The aim of this study was to examine whether the level of PG after ESD can be used to predict the risk of metachronous cancer. Patients and Methods: The study included of 100 consecutive patients who underwent ESD for gastric cancer at Hirosaki University Hospital from September 2009 to February 2011. Serum levels of PG I and II on the day before and after ESD were compared. Stool antigen test was also performed to examine the presence of Helicobacter pylori infection. Results: The mean serum level of PG I before and after ESD was 34.3 ± 31.6 ng/mL and 70.5 ± 100.0 ng/mL (P < 0.001), respectively. PG I/II ratio before and after ESD was 2.40 ± 1.51 and 2.79 ± 1.70 (P < 0.001). The serum level of PG I and the PG I/II ratio were significantly changed after ESD, regardless of the use of proton pump inhibitor, Helicobacter pylori infection or the location of the tumor. Conclusions: ESD treatment modulates the serum level of PG I and significantly increases the PG I/II ratio. Serum levels of PG should be measured before the ESD procedure is performed to predict the risk of developing metachronous gastric cancer after ESD.     

Serum Group I Pepsinogens and Gastrin in Relation to Gastric H+ and Pepsin Outputs before and after Subcutaneous Injection of Pentagastrin

A conventional pentagastrin test was carried out in 25 patients with dyspeptic complaints, and gastric H⁺ and pepsin outputs were determined. Blood was drawn before the intubation and 5 and 30 min after subcutaneous injection of pentagastrin, and serum group I pepsinogens (PG I) and serum gastrin were determined by radioimmunoassay methods. A significant correlation was found between serum PG I, on the one hand, and basal gastric pepsin output as well as pentagastrin-stimulated gastric H⁺ and pepsin outputs, on the other. Basal serum gastrin was also significantly correlated to pentagastrin-stimulated gastric pepsin output as well as to serum PG I. Pentagastrin failed to induce an increase in serum PG I during the first 30 min.     

Gastric Acid Secretion,Serum Pepsinogen I,and Serum Gastrin in Japanese with Gastric Hyperplastic Polyps or Polypoid-Type Early Gastric Carcinoma

We determined the maximum secretion of gastric acid and the fasting serum levels of pepsinogen I and gastrin in Japanese patients with gastric hyperplastic polyps or polypoid-type early gastric carcinoma, comparing those findings with observations in control subjects. Both the maximum acid secretion and fasting levels of serum pepsinogen I were significantly lower in the patients with gastric hyperplastic polyps or polypoid-type early gastric carcinoma than in the controls. Fasting serum gastrin levels were significantly higher in the patients with gastric hyperplastic polyps than in the other two groups of subjects. These data demonstrated that the combination of hypochlorhydria, a low level of pepsinogen I, and hypergastrinemia (type-A gastritis) was common in the patients with gastric hyperplastic polyps, whereas hypochlorhydria and a low pepsinogen I without hypergastrinemia (type-B gastritis) were common in those with polypoid-type early gastric carcinoma.     

益气化瘀阻萎方通过调控PI3K/AKT信号通路缓解慢性萎缩性胃炎的实验研究

[目的] 探讨益气化瘀阻萎方对慢性萎缩性胃炎(chronic atrophic gastritis，CAG)模型小鼠的作用及其可能的机制。[方法] 将昆明小鼠随机分为空白对照组，模型组，益气化瘀阻萎方低、高剂量组，通过2%水杨酸钠溶液灌胃结合游泳的方法复制CAG模型，建模成功后，益气化瘀阻萎方低、高剂量组给予益气化瘀阻萎方溶液灌胃治疗，空白对照组和模型组灌胃等量0.9%氯化钠溶液。4周后取材，苏木素-伊红(hematoxylin-eosin，HE)染色观察小鼠胃组织病理学变化，酶联免疫吸附试验(enzyme-linked immunosorbent assay，ELISA)检测血清中胃蛋白酶原Ⅰ(pepsinogen Ⅰ，PG Ⅰ)、PG Ⅱ水平及PGⅠ/PGⅡ的变化，免疫印迹试验检测胃组织中磷脂酰肌醇3-激酶/蛋白激酶B(phosphatidylinositol 3-kinase/protein kinase B，PI3K/AKT)信号通路蛋白表达水平。[结果] 与模型组比较，益气化瘀阻萎方低、高剂量组小鼠胃组织结构紧密，黏膜层增厚，且给药组小鼠血清中PGⅠ、PGⅡ水平及PGⅠ/PGⅡ显著增高(P<0.01)；给药组小鼠胃组织中PI3K、AKT、磷酸化-AKT(phospho-AKT，p-AKT)蛋白表达水平均显著降低(P<0.05，P<0.01)。[结论] 益气化瘀阻萎方对CAG小鼠胃黏膜组织具有保护作用，其机制可能与抑制PI3K/AKT信号通路活化有关。     

Exploring the spectrum of incidental gastric polyps in autoimmune gastritis

BackgroundGastric polyps represent an abnormal proliferation of the gastric mucosa. Chronic atrophic autoimmune gastritis (CAAG) targets parietal cells and results in hypo-achlorhydria and hypergastrinemia, which exerts a proliferative effect on the gastric mucosa.AimsWe investigate the incidence of gastric polyps in CAAG patients.MethodsThis is a single-center retrospective study examining patients with confirmed CAAG from January 1990 until June 2022. Demographic, clinical, biochemical, and serological data were collected for each included patient. The histopathological characteristics of the detected polyps were recorded.ResultsA total of 176 CAAG patients were included. Eighty-nine (50.5%) had 163 incidental polyps. Seventy-six patients (85%) had 130 non-endocrine lesions, among which 118 (90.7%) were inflammatory, 6 (4.6%) adenomatous, and 4 (3%) fundic; 33 patients (37%) had gastric neuroendocrine neoplasms (gNENs), and 21 (23.6%) both; one had MALToma and one gastric adenocarcinoma. Higher circulating levels of gastrin and chromogranin A were observed among patients with polyps (median 668 vs 893 pg/ml p = 0.0237, 146 vs 207 ng/ml p = 0.0027, respectively).ConclusionCAAG implies a high incidence of gNENs and exocrine lesions. Gastrin plays a possible trophic role on the mucosa. Further evidence is needed to validate its predictive role for increased polyp risk in CAAG.