Clinical consequences of controversies in gastric physiology

Abstract

Studies on the regulation of gastric acid secretion started more than 100 years ago at an early phase of experimental physiology. In nearly the whole last century there were disputes about the interpretation of the findings: the interaction between the three principle gastric acid secretagogues acetylcholine, gastrin and histamine, the cell producing the relevant histamine which turned out to be the ECL cell, the ability of the ECL cell to divide and thus develop into tumours, the classification of gastric carcinomas and the mechanism for Helicobacter pylori carcinogenesis. The elucidation of the central role of the ECL cell and thus its main regulator, gastrin, solve all these controversies, and gives a solid base for handling upper gastrointestinal diseases.     

幽门螺杆菌阳性胃溃疡除菌治疗的临床研究

目的研究根除幽门螺杆菌（Hp）治疗对Hp阳性的胃溃疡愈合率、愈合质量及复发的影响。方法将68例Hp阳性的胃溃疡患者随机分为除菌组和非除菌组，除菌组给予奥美拉唑20mg＋阿莫西林0．5g＋呋喃唑酮0．1g口服，2次／d，1周后奥美拉唑改为20mg，1次／d，共治疗4周。非除菌组单独给予奥美拉唑，剂量方法同上。分别于4周及1年后复查胃镜。结果除菌组和非除菌组比较，4周后溃疡愈合率差异无统计学意义（分别为97．4％和90％，P〉0．05），但两组溃疡愈合质量比较差异有统计学意义。1年后两组溃疡复发率比较，除菌组低于非除菌组，差异有统计学意义（分别为6．7％和59．3％，P〈0．01），Hp根除率除菌组高于非除菌组，差异有统计学意义（分别为86．7％和3．7％，P〈0．01）。结论Hp感染与胃溃疡存在相关性，根除Hp治疗不仅可以提高溃疡的愈合质量，而且还可以减少溃疡的复发。     

Relation of Helicobacter pylori Infection and Angiographically Demonstrated Coronary Artery Disease

Conventional coronary risk factors explain only part of the variation in the incidence of cases of coronary heart disease. Recently H. pylori genomic material has been demonstrated in the coronary arteries of myocardial infarct. In searching for additional coronary risk factors, the potential role of H. pylori infection deserves to be investigated. To clarify if H. pylori infection is associated with an increased risk of coronary heart disease, a series of patients admitted to the Cardiac Catheterization Laboratory for coronary angiography were recruited prospectively. Cases (N = 165) were defined as those who had at least one coronary artery lesion occupying at least 50% of the luminal diameter on coronary angiography. Patients who had normal coronary angiography were selected as controls (N = 127). Demographic data, cardiovascular risk factors, and socioeconomic status were measured in both of the patients and controls. Stored serum specimens from both groups were tested for the presence of serum IgG antibody to H. pylori using enzyme-linked immunosorbent assay; 69.1% of the cases and 77.2% of the controls were seropositive for H. pylori (odds ratio 0.66, 95% CI 0.38–1.16, P = 0.12). After adjustment for age, gender, cardiovascular risk factors, and socioeconomic class, this remained nonsignificant (odds ratio 0.59, 95% CI 0.32–1.09, P = 0.09). H. pylori seropositivity was not associated with several coronary risk factors in either cases or controls. The proportion of H. pylori-positive patients was higher among the cases with triple vessel disease (77.5%) than those with double vessel disease (67.3%) and single vessel disease (65.7%); however, the differences were not statistically significant (odds ratio 0.57, 95% CI 0.23–1.4, P = 0.19). In this study no increase was found in H. pylori seropositivity in subjects with coronary artery disease. This minor association suggests that previous H. pylori infection, reflecting the early childhood environment, may not be important in determining the risk of coronary heart disease.     

Altered Gastrin Regulation in Mice Infected with Helicobacter felis

Altered gastrin expression associated with Helicobacter pylori infection may contribute to the pathogenesis of peptic ulcer disease or gastric cancer in man, but gastrin has not been investigated in a murine model of Helicobacter infection. C57BL/6 mice were inoculated with Helicobacter felis and examined after 4–21 weeks for G and D cell numbers, antral gastrin and somatostatin mRNA, and luminal pH. In H. felis-infected mice, gastrin mRNA declined at four and six weeks after infection to 57% and 23%, respectively, of uninfected control values. Concurrently, somatostatin mRNA showed no change at four weeks and a modest 25% decrease at six weeks after infection. Similar reductions were noted in G and D cell numbers, resulting in a decrease in the G/D cell ratio after mice were infected with H. felis. Infected animals also showed a loss of parietal and chief cells, and an increased gastric pH. H. felis infection in C57BL/6 mice leads to an early suppression of G cell number and gastrin mRNA. These changes precede an alteration in somatostatin cell number and mRNA and, coupled with reductions in parietal and chief cells, may contribute both to severe impairment of gastric acid output and the potential for carcinogenic processes.     

益生菌联合三联疗法治疗幽门螺杆菌相关性慢性胃炎的临床效果

目的：观察益生菌联合三联疗法治疗幽门螺杆菌相关性慢性胃炎的临床效果及预后。方法选择深圳市石岩人民医院2013年3月~2014年1月收治的幽门螺杆菌相关性慢性胃炎患者110例作为研究对象,并将其按奇偶数随机分为对照组（50例）和治疗组（60例）。对照组给予单纯三联疗法（奥美拉唑40 mg,2次/d+克拉霉素0.5 g,2次/d+阿莫西林1.0 g,2次/d）治疗;治疗组在此基础上加用益生菌（双歧杆菌乳杆菌三联活菌片,1片/次,3次/d）。观察比较两组治疗4周后临床效果及不良反应发生情况,随访1年后,观察复发率。结果对照组痊愈13例,显效18例,有效11例,总有效率为84.0%;治疗组痊愈22例,显效25例,有效11例,总有效率为96.7%,治疗组总有效率显著高于对照组,差异有统计学意义（P<0.05）;随访1年后,治疗组复发率（6.7%）显著低于对照组（22.0%）,差异有统计学意义（P<0.05）。对照组有6例（12.0%）出现不良反应,其中恶心2例,呕吐1例,头晕3例;治疗组有2例（3.3%）出现不良反应,其中恶心1例,头晕1例,两组不良反应发生率比较差异无统计学意义（χ2=1.89,P>0.05）。结论益生菌联合三联疗法治疗幽门螺杆菌相关性慢性胃炎效果良好,并可有效降低复发率。     

DoesHelicobacter pylori-induced gastritis enhance food-stimulated insulin release?

The fact thatH. pylori gastritis results in an increased secretion of basal and meal-stimulated gastrin, which is also a physiologic amplifier of insulin release directed us to investigate whetherH. pylori gastritis may lead to an enhancement of nutrient-stimulated insulin secretion. For this purpose, we have investigated the insulin responses to both oral glucose and a mixed meal in 15 patients withH. pylori gastritis before and one month after the eradication therapy and also in 15H. pylori-negative control subjects. The areas under the curve (AUC) for serum insulin following both oral glucose and a mixed meal in the patients withH. pylori gastritis before the eradication were significantly (P<0.05) higher than those in theH. pylori-negative controls. After the eradication ofH. pylori, the AUC for serum insulin following oral glucose and mixed meal decreased by 9.4% and 13.1%, respectively (P<0.001 in both), and serum basal and meal-stimulated gastrin levels decreased significantly (P<0.001). These results suggest thatH. pylori gastritis enhances glucose and meal-stimulated insulin release probably by increasing gastrin secretion.Presented in part as an abstract at the 8th Balkan Congress of Endocrinology, Bursa, Turkey, May 3–5, 1995.     

Infective dyspepsia in a heart transplant recipient

We report the coexistence of symptomatic viral, bacterial, and fungal infection of the upper gastrointestinal tract in a heart transplant recipient. Endoscopic findings were normal at all levels but, because of severe symptoms and recent conversion to positive serology forCytomegalovirus, biopsies were taken. These showed esophageal candidiasis and gastricHelicobacter infection that has hitherto been unreported in cardiac transplant recipients.     

Microbiota in the stomach and application of probiotics to gastroduodenal diseases

The stomach is a hostile environment for most microbes because strong gastric acid kills indigenous microorganisms. Thus, the mass of indigenous microbes detected by traditional culturing method in a highly acidic stomach is reported to be very small. However, in a stomach with less acidity due to atrophic changes of the gastric mucosa, the number of live gastric microbiota dramatically increases and their composition changes. A probiotic is defined as a live microorganism that, when administered in adequate amounts, confers a health benefit on the host. The administration of probiotics to the stomach has thus far been considered impractical, mainly due to the strong acidity in the stomach. The identification of candidate probiotic strains with sufficient resistance to acidity and the ability to achieve close proximity to the gastric mucosa could enable the application of probiotics to the stomach. The utilization of probiotics alone for Helicobacter pylori (H. pylori) infection significantly improves gastric mucosal inflammation and decreases the density of H. pylori on the mucosa, although complete eradication of H. pylori has not yet been demonstrated. The use of probiotics in combination with antimicrobial agents significantly increases the H. pylori eradication rate, especially when the H. pylori strains are resistant to antimicrobial agents. While H. pylori has been considered the most important pathogenic bacterium for the development of gastric cancer, bacteria other than H. pylori are also suggested to be causative pathogens that promote the development of gastric cancer, even after the eradication of H. pylori. Increased non-H. pylori Gram-negative bacteria in the stomach with weak acidity accompanying atrophic gastritis may perpetuate gastric mucosal inflammation and accelerate carcinogenic progression, even after H. pylori eradication. Probiotics restore the acidity in this stomach environment and may therefore prevent the development of gastric cancer by termination of Gram-negative bacteria-induced inflammation. Functional dyspepsia (FD) is defined as the presence of symptoms that are thought to originate in the gastroduodenal region in the absence of any organic, systematic or metabolic diseases. Accumulating evidence has pointed out the duodenum as a target region underlying the pathophysiology of FD. A randomized placebo-controlled clinical trial using a probiotic strain (LG21) demonstrated a significant improving effect on major FD symptoms. One of the possible mechanisms of this effect is protection of the duodenal mucosa from injurious intestinal bacteria through the resolution of small intestinal bacterial over growth.     

Development of Epstein-Barr virus-associated gastric cancer: Infection,inflammation, and oncogenesis

Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) cells originate from a single-cell clone infected with EBV. However, more than 95% of patients with gastric cancer have a history of Helicobacter pylori (H. pylori) infection, and H. pylori is a major causative agent of gastric cancer. Therefore, it has long been argued that H. pylori infection may affect the development of EBVaGC, a subtype of gastric cancer. Atrophic gastrointestinal inflammation, a symptom of H. pylori infection, is observed in the gastric mucosa of EBVaGC. Therefore, it remains unclear whether H. pylori infection is a cofactor for gastric carcinogenesis caused by EBV infection or whether H. pylori and EBV infections act independently on gastric cancer formation. It has been reported that EBV infection assists in the onco-genesis of gastric cancer caused by H. pylori infection. In contrast, several studies have reported that H. pylori infection accelerates tumorigenesis initiated by EBV infection. By reviewing both clinical epidemiological and experimental data, we reorganized the role of H. pylori and EBV infections in gastric cancer formation.     

Rifabutin as salvage therapy for Helicobacter pylori eradication: Cornerstones and novelties

When several Helicobacter pylori eradication treatments fail, guidelines recommend a cultured guided approach; however, culture is not widely available. Therefore, a rifabutin based regimen could be the best solution. Rifabutin indeed shows a low rate of antibiotic resistance. Rifabutin is generally used in combination with amoxicillin in a triple therapy, with eradication rates about 80% in third-line regimens. The ideal duration of this therapy should range between 10 and 12 d. Combinations with antibiotics other than amoxicillin have demonstrated even better results, such as vonoprazan, which is a type of novel acid suppressor drug. Finally, a new formulation of triple therapy in a single capsule is under investigation, which is a field that deserves further investigation. Some notes of caution about rifabutin should be mentioned. This drug is used to treat tuberculosis or atypical mycobacteria; therefore, before starting a rifabutin-based eradication regimen, Mycobacterium tuberculosis infection should be thoroughly tested, since its use could promote the development of antibiotic resistance, thus affecting its effectiveness against Koch’s bacillus. Additionally, some serious side effects must be evaluated before starting any rifabutin-based therapy. Adverse effects include fever, nausea, vomiting and bone marrow suppression. For this reason, full blood count surveillance is required.