Cost-Effectiveness of Eradication of Helicobacter pylori in Gastric Cancer Survivors After Endoscopic Resection of Early Gastric Cancer

Background:  Clinical effectiveness of Helicobacter pylori eradication in gastric cancer survivors after endoscopic resection of early gastric cancer (EGC) was recently established in a randomized controlled trial. We aimed to establish long-term cost-effectiveness in gastric cancer survivors after endoscopic resection of EGC.
Materials and Methods:  A Markov model was constructed to compare the costs and outcomes of the two intervention strategies: (1) eradicate H. pylori after complete resection of EGC by endoscopy (2) do not eradicate. Estimates for variables in the model were obtained by extensive review of published reports. Analyses were made from the Korean public healthcare provider's perspective.
Results:  Base-case analysis indicated H. pylori eradication costs less (US$ 29,780 vs. US$ 30,594) than no eradication, and save more lives (mean life expectancy from eradication: 13.60 years vs. 13.55 years). One-way and three-way sensitivity analyses showed the robustness of the cost-effectiveness results.
Conclusion:  In this selective population with very high risk of developing gastric cancer, H. pylori eradication should be considered for reimbursement with priority to prevent subsequent cancer and also reduce health care cost.     

Helicobacter pylori Eradication Therapy May Facilitate Gastric Ulcer Healing After Endoscopic Mucosal Resection: A Prospective Randomized Study

Background and Aim: It remains unclear whether Helicobacter pylori eradication therapy affects the healing rate of iatrogenic ulcers following endoscopic mucosal resection (EMR) for gastric tumors. The aim of our study was to prospectively evaluate the effect of H. pylori eradication therapy on gastric ulcer healing after EMR. Methods: After EMR, patients were randomly assigned to either the H. pylori eradication group (Hp group) (lansoprazole 30 mg, amoxicillin 1000 mg, and clarithromycin 500 mg, twice a day for 7 days) or the noneradication group (proton pump inhibitor, PPI group) (lansoprazole 30 mg, twice a day for 7 days). Four weeks after EMR, the ulcer stages and size were compared between the two groups. Moreover, ulcer‐related symptoms, bleeding rates, adverse effects, and drug compliance were compared. Results: A total of 64 patients were enrolled. Of these, 17 patients were excluded from the study. The two groups were comparable in terms of baseline clinicopathologic characteristics. Four weeks after EMR, the two groups did not differ with respect to ulcer stage (p = .475) or ulcer‐related symptoms (p = .399). However, the ulcer reduction ratio was significantly higher in the Hp group (0.028 ± 0.024 vs. 0.065 ± 0.055, p < .05). No differences were observed between the two groups with regard to drug compliance, adverse drug event rates, or bleeding rates. Conclusions: Our results suggest that H. pylori eradication therapy might improve the ulcer healing rate after EMR.     

胃黏膜菌群与幽门螺杆菌的相关性

除幽门螺杆菌之外,胃黏膜内还定居着大量细菌,占主导地位的是厚壁菌门、变形菌门、拟杆菌门、放线菌门和梭杆菌门。幽门螺杆菌和胃黏膜菌群之间可通过竞争营养和空间、扰乱抑菌肽的分泌以及改变宿主胃生理环境等直接或间接相互影响。本研究总结了胃内正常菌群的组成特征,分析了胃黏膜菌群与幽门螺杆菌之间的相互关系及其潜在机制,并进一步探讨了胃黏膜菌群对幽门螺杆菌相关胃部疾病的影响,有利于深入理解慢性胃病的发病机制,为疾病预防及治疗提供理论依据。     

Gastric juice neopterin in Helicobacter pylori infection

Abstract Neopterin, a pteridine compound produced by macrophages activated by interferon-gamma, is widely used to assess the activation of cellular immunity. An elevation in serum or urinary neopterin reflects immune activation in many different disorders, including viral infections, cancer, autoimmune diseases or acute myocardial infarction, but less attention has been paid to neopterin concentration in other biological fluids. The aim of the present study was to examine neopterin concentration in gastric juice. An association with the presence of Helicobacter pylori , a bacterium linked to the most common disorders of upper digestive tract, was also investigated. Gastric juice was obtained at endoscopy from 61 patients. Neopterin was determined by a radioimmunoassay and the presence of H. pylori was examined by urease test. The macroscopic finding of bile in gastric juice was associated with significantly higher neopterin levels compared to patients where no bile was noted (15.5 ± 15.6 vs. 2.1 ± 3.0 nmol/l, P < 0.001). However, similar concentrations were observed in the H. pylori positive and H. pylori negative patients (7.6 ± 12.0 vs. 11.1 ± 14.9 nmol/l). Even in the absence of macroscopic bile contamination, no significant difference could be found between the infected and uninfected patients (2.3 ± 3.2 vs. 1.3 ± 1.9 nmol/l), and the patients with duodenal ulcer and normal findings (3.8 ± 4.6 vs 1.6 ± 1.9 nmol/l). The contamination of gastric juice with bile represents the limitation for the use of neopterin as a marker of immune activation in the gastric mucosa. Rather than an index of immune activation, gastric juice neopterin concentration represents a marker of duodenogastric reflux.     

Helicobacter pylori and Clinical Aspects of Gastric Cancer

In spite of important new insights into the basic mechanisms of gastric carcinogenesis, progress in the management of gastric cancer has been modest. Some modifications in the chemotherapies used for palliation and strategies for downstaging of the disease prior to surgical intervention are noteworthy. The positive experience with endoscopic mucosal resection (EMR) and submucosal dissection (ESD) for treatment of early gastric cancer has been confirmed and extended. The procedure-related morbidity and post-interventional quality of life is clearly favorable compared to open surgical resection in well-selected patients. New data on Helicobacter pylori revealed that eradication after endoscopic resection of early gastric cancer significantly reduces the incidence of recurrent and metachronous gastric neoplasias. It can further improve healing rates of treatment induced gastric ulcers. Eradication therapy therefore remains the best target for prevention of the disease. Critical is the "point of no return" when mucosal alterations (i.e. intestinal metaplasia, glandular atrophy) are no longer reversible. A population-based screen-and-eradicate strategy for H. pylori infection can at present only be recommended in high incidence regions.     

Effect of Helicobacter pylori Eradication on Incidence of Gastric Cancer in Human and Animal Models: Underlying Biochemical and Molecular Events

Background:  Gastric cancer remains one of the most common cancers worldwide. A strong association exists between Helicobacter pylori infection and the risk of developing noncardia gastric cancer. H. pylori eradication by antibiotic treatment is regarded as a primary chemoprevention strategy to reduce gastric cancer incidence.
Aim:  To analyze the efficacy of H. pylori eradication in preventing gastric cancer in human and animal models, and to discuss whether biochemical, genetic, and epigenetic changes associated with H. pylori infection are reversible after curing the infection.
Results:  Several intervention trials have indicated that in some patients, H. pylori eradication leads to regression and prevents the progression of precancerous lesions. The eradication therapy reduces gastric cancer incidence in patients without any precancerous lesions at the baseline and is most effective before the development of atrophic gastritis. A few recent intervention studies in Japan have demonstrated significant prophylactic effects of eradication therapy on the development of gastric cancer, suggesting the use of eradication therapy in high-risk populations as a gastric cancer reduction strategy. However, gastric cancer may still develop despite successful eradication therapy. Studies in animal models have confirmed the use of eradication therapy at an early point of infection to prevent gastric cancer development.
Conclusion:  H. pylori eradication may not completely abolish the risk of gastric cancer. However, eradication therapy may be used in high-risk populations to reduce gastric cancer incidence. It can reverse many biochemical, genetic, and epigenetic changes that H. pylori infection induces in the stomach.     

霉菌、幽门螺杆菌及双菌种感染在胃溃疡、胃癌中检出的意义

探讨霉菌、幽门螺杆菌(Hp)单菌种感染和霉菌、Hp(双菌种)同时感染在胃癌及胃溃疡中的组织病理学变化、发病情况及意义。采用常规石蜡切片,HE染色和PAS、Giemsa特殊染色、免疫组织化学染色及PCR方法,对223例慢性浅表性胃炎、111例慢性萎缩性胃炎、116例胃溃疡、121例胃癌纤维胃镜活检标本进行回顾性研究。结果显示,慢性浅表性胃炎、慢性萎缩性胃炎未检出双菌种感染。胃溃疡双菌种感染11例,检出率9.5%;胃癌双菌种感染21例,检出率17.4%。双菌种感染在胃癌及胃溃疡中的发现,表明双菌种感染可能是导致胃溃疡、胃癌发生的又一致病因素。     

Helicobacter pylori Infection, Intestinal Metaplasia, and Gastric Cancer Risk in Eastern Siberia

Background: The incidence of gastric cancer (GC) is extremely high in Russia and eastern Siberia, where information on the epidemiology of Helicobacter pylori infection is fragmentary. Aims: To assess the prevalence of both H. pylori infection (including CagA status) and intestinal metaplasia (IM) in Russian and eastern Siberian populations carrying a different risk of GC. Materials and Methods: A sample of 2129 consecutive patients was considered, including 689 Europoids and 1440 Mongoloids (493 Evenks, 533 Khakass people, and 414 Tuvans), who all underwent serum sampling and upper gastrointestinal endoscopy. H. pylori status was established (ELISA, urease test, and histology), and IgG anti‐CagA antibodies were assessed (ELISA) in H. pylori‐positive cases. At least 3 biopsy samples per patient were considered, and IM was scored as present versus absent. The prevalence of H. pylori, CagA+ve status, and IM was compared with the incidence of GC according to the regional cancer registries. Results: The prevalence of H. pylori was similar for the Europoids and Mongoloids (93.6 vs 94.3%). The prevalence of CagA+ve infection was as follows: Europoids 61.2%, Evenks 36.4%, Khakass 44.0%, Tuvans 60.0% (p_1vs2 < .001; p_1vs3 < .001; p_2vs4 < .001; p_3vs4 < .001). The prevalence of IM was as follows: Europoids 10.7%, Evenks 5.1%, Khakass 9.8%, and Tuvans 23.4% (p_1vs2 = .001; p_1vs4 < .001; p_2vs4 < .001; p_3vs4 < .001). The incidence of GC (per 100,000 population/year) was as follows: Europoids 33.2; Evenks 18.2; Khakass 20.2; Tuvans 50.7 (p_1vs2 = 0.04; p_1vs3 = .05; p_2vs4 < .001; p_3vs4 < .001). Conclusion: H. pylori infection is consistently high in Russian and eastern Siberian populations; ethnicities with similar prevalence of CagA+ve status had different prevalence of IM and incidence of GC. As expected, IM prevalence correlated with the incidence of GC. Host‐related and/or environmental factors may explain discrepancies between H. pylori status, the prevalence of IM, and the incidence of GC.     

胃溃疡、胃癌组织中幽门螺杆菌及真菌基因片段的扩增分析

探讨胃溃疡、胃癌组织中幽门螺杆菌(Helicobacter pylori,Hp)、真菌(Fungi)单纯感染及混合感染的可能性并进行验证。应用聚合酶链反应(PCR)技术,分别自4例胃溃疡和4例胃癌并伴单纯幽门螺杆菌、真菌及其混合感染病例石蜡包埋组织(FFPE)中扩增Hp及fungi基因特异片段并进行测序分析。成功提取了FF-PE胃组织基因组DNA,并扩增出Hp 16S rRNA及真菌内转录间隔区18S rDNA基因和28S rDNA之间的基因特异条带,测序大小分别为114 bp和357 bp,经在线BLAST比对分析表明所扩增基因与Hp及真菌核苷酸具有高度同源性。胃溃疡、胃癌组织中存在Hp和真菌单纯感染及混合感染。推测Hp与真菌混合感染可能是加重胃溃疡发展和诱发胃癌发生的又一致病因素。积极治疗Hp与真菌混合感染有助于提高胃溃疡的治愈率和减少胃癌的发生。     

幽门螺杆菌相关胃癌发生不同阶段miRNAs表达与临床研究

目的 观察幽门螺杆菌（Helicobacter pylori, H. pylori）感染的慢性非萎缩性胃炎（no-atrophic gastritis,NAG）→萎缩性胃炎（chronic atrophic gastritis,CAG）→肠上皮化生（intestinal metaplasia,IM）→非典型增生（dysplasia,DYS）→胃癌（gastric cancer,GC）五个不同阶段miR-1、miR-20a、miR-34a、miR-423-5p表达变化规律及其与临床的关系。方法 收集胃镜及病理证实的上述胃癌发生五个不同阶段且H. pylori感染的患者（依次为44、47、43、50、45例）,胃癌无H. pylori感染者46例,胃黏膜正常（normal gastric mucose,NGM）63例的血清标本,采用Real-time PCR法检测无H. pylori感染者miR-1、miR-20a、miR-34a、miR-423-5p表达。结果 H. pylori感染NAG→GC不同阶段,miR-1、miR-20a、miR-34a、miR-423-5p表达逐渐升高（P<0.05）,GC阶段最高,miR-1、miR-20a CAG→GC阶段均高于NGM（P<0.05）,与NGM比较差异有统计学意义（P<0.05）;其表达程度与GC发生阶段呈正相关（P<0.001）;GC组H. pylori感染者较无H. pylori感染者miR-1、miR-20a、miR-34a、miR-423-5p表达升高（P<0.05）。结论 H. pylori感染CAG→GC阶段miR-1、miR-20a、miR-34a、miR-423-5p表达升高,向胃癌演进中呈逐渐升高趋势,miR-1、miR-20a、miR-34a、miR-423-5p高表达可能是H. pylori感染后导致胃癌发生发展的重要机制,miR-1、miR-20a、miR-34a可作为诊断早期胃癌的标记物。     

Helicobacter pylori Eradication Prevents Metachronous Gastric Neoplasms after Endoscopic Resection of Gastric Dysplasia

Purpose

There is insufficient data about the role of eradication of H. pylori after endoscopic resection (ER) for gastric dysplasia. The aim was to investigate the benefit of H. pylori eradication after ER in patients with gastric dysplasia to prevent metachronous gastric neoplasms.

Materials and Methods

We retrospectively reviewed 1872 patients who underwent ER of gastric dysplasia. We excluded patients with a follow-up period of <2 years or who had not undergone tests for active H. pylori infection. A total of 282 patients were enrolled. The patients were categorized into those without active H. pylori infection (H. pylori-negative group, n = 124), those who successfully underwent H. pylori eradication (eradicated group, n = 122), and those who failed or did not undergo H. pylori eradication (persistent group, n = 36).

Results

Metachronous recurrence was diagnosed in 36 patients, including 19 in the H. pylori-negative group, 10 in the eradicated group, and 7 in the persistent group. The cumulative incidence of metachronous recurrence was significantly lower in the H. pylori-eradicated group in comparison with either of the H. pylori-persistent (non-eradicated or failed) groups (p = 0.039). Similarly, the incidence of metachronous recurrence was significantly lower in the H. pylori-eradicated group compared with the H. pylori-negative group (p = 0.041).

Conclusion

Successful H. pylori eradication may reduce the development of metachronous gastric neoplasms after ER in patients with gastric dysplasia.     

Helicobacter pylori antibodies and gastric cancer: a gender-related difference

Helicobacter pylori has been proposed as a causative agent of gastric cancer. The aim of this study was to define serum antibodies response against different H. pylori antigens in patients with gastric cancer. Serum samples were collected from 115 Lithuanian patients with non-cardia gastric cancer and 110 age- and sex-matched controls without cancer. Heat-stable, low-molecular-mass, and outer membrane proteins were used as antigens to analyze serum IgG antibody response against H. pylori by enzyme-linked immunosorbent assay. Seroprevalence of H. pylori using low-molecular-mass antigen was significantly higher in gastric cancer patients, compared to controls (77% versus 57%, p<0.05). Significant differences in the prevalence of H. pylori infection between gastric cancer patients and controls were found in females using all three studied antigens: heat-stable (98% versus 84%, p<0.05), low-molecular-mass (88% versus 48%, p<0.05) and outer membrane proteins (78% versus 57%, p<0.05). In males, no significant differences were revealed between gastric cancer patients and controls. There may be other cofactors in addition to H. pylori that are important for the development of gastric cancer. H. pylori seems, however, to be a more important for development of gastric cancer in females than in males or males may have more confounding risk factors for gastric cancer than females.     

Helicobacter pylori Infection and Family History of Gastric Cancer Decrease Expression of FHIT Tumor Suppressor Gene in Gastric Mucosa of Dyspeptic Patients

Background:  The expression of a fragile histidine triad (FHIT) protein is lost in stomach tumors. The study aimed at determining whether FHIT expression is affected by Helicobacter pylori infection, strain virulence ( vacA and cagA genes) and histopathological changes in the gastric mucosa of patients with functional dyspepsia having first-degree relatives with gastric cancer.
Materials and Methods:  Eighty-eight never-smoking patients with functional dyspepsia were selected for the study, and 48 of them had first-degree relatives with gastric cancer. Bacterial DNA amplification was used to identify H. pylori colonization. The level of FHIT gene expression was determined by qRT-PCR (mRNA) and Western blot (FHIT protein) analyses.
Results:  For patients having first-degree relatives with gastric cancer FHIT expression was lower (mRNA by ca. 40–45% and protein by 30%) compared with the control patients ( p  < .05). H. pylori infection decreased the FHIT mRNA level by 10–35% and the protein level by 10–20%. Bacterial strain vacA (+) cagA (+) lowered FHIT mRNA by ca. 30–35% in the antrum samples of both groups and in corpus samples of patients with first-degree relatives with gastric cancer ( p  < .05). The FHIT mRNA level was twice as high in control H. pylori- negative patients with intestinal metaplasia, compared with those with non-atrophic gastritis.
Conclusions:  The decreased FHIT gene expression associated with hereditary factors and with H. pylori infection, especially with vacA (+) cagA (+)-positive strains, may be related to gastric carcinoma development.     

MIF mRNA在胃窦胃癌组织中的表达及其与幽门螺杆菌感染的关系

目的:探讨胃窦胃癌组织中人巨噬细胞移动抑制因子MIF mRNA的表达,并分析其与幽门螺杆菌感染的关系,分析二者在胃窦胃癌发生中的相关性。方法:选取2013年1月至2014年12月于我院收治的胃窦胃癌患者30例作为观察组,另随机选择10例胃窦胃炎患者作为对照组,采用14C-尿素呼气试验(UBT)检测各组患者有无幽门螺杆菌感染,定量逆转录PCR检测观察组患者及对照组患者组织中MIF mRNA表达。统计分析不同组织中MIF mRNA表达与幽门螺杆菌感染之间的关系。结果:观察组组织中MIF mRNA的表达为(1.09±0.11),高于对照组组织的(0.21±0.08),差异具有统计学意义(P0.05)。进一步亚组分析,观察组合并幽门螺杆菌感染组织中MIF mRNA的表达为(1.24±0.14),高于非幽门螺杆菌感染者的(1.09±0.11),差异具有统计学意义(P0.05)。结论:MIF mRNA在胃窦胃癌组织中高表达,幽门螺杆菌感染促进了MIF mRNA的表达,共同促进了胃窦胃癌的发生发展。