根除幽门螺杆菌可否作为胃癌的化学预防手段?

幽门螺杆菌感染是慢性胃炎、消化性溃疡的主要病因.也是胃癌的Ⅰ类致癌原.根除幽门螺杆菌后,胃黏膜炎症得以明显改善,是否胃黏膜萎缩、肠化也能因此而逆转,并成为胃癌的化学预防手段之一?本文对现有的研究结果进行了系统评述,认为根除幽门螺杆菌感染是一种潜在的化学预防胃癌的措施,尤其对于高危人群,应检测并根除幽门螺杆菌,进行胃癌预防.     

根除幽门螺杆菌预防胃癌:希望和困惑

胃癌仍是我国最常见的恶性肿瘤之一。幽门螺杆菌感染是肠型胃癌发生的先决条件,其根除可降低胃癌发生危险性。但幽门螺杆菌感染者中最终仅<1%的患者发生胃癌,环境因素和遗传因素在一些患者中起重要作用。根除幽门螺杆菌作为胃癌一级预防策略已被提出。但是,是普遍筛查幽门螺杆菌感染和治疗所有阳性者,还是根据当地条件,在评估可行性、疗效和不良反应后进行实施尚有争议。基于我国情况,当前似乎采取后一种策略更加妥当。     

胃癌预防亚太地区共识指南

背景与目的：胃癌是亚太地区的主要健康负担之一，但对其预防策略尚缺乏共识。本共识会议旨在评价预防胃癌的策略。方法：多学科专家组应用德尔菲（Delphi）法制订共识条文，提呈相关数据，对证据等级、推荐强度以及共识水平予以分级。结果：幽门螺杆菌（H.pylori）感染是非贲门胃腺癌必要但非充分的致病因子。盐的高摄人与胃癌强烈相关。新鲜果蔬对胃癌具有预防作用，但维生素和其他饮食补充并不能预防胃癌。Hprtori感染中的宿主-细菌相互作用导致不同类型的胃炎和胃酸分泌，从而决定疾病结局。胃癌阳性家族史是一个重要的危险因素。低血清胃蛋白酶原反映胃萎缩程度，可作为检出胃癌高危人群的标志物。H．prlori筛查和治疗被推荐作为减少高危人群胃癌危险性的一种策略．该策略在萎缩性胃炎发生前实施最为有效，但并不排除对胃癌高危人群的内镜监测。对胃癌低危人群不推荐行H．pylori筛查。H．pylori感染的一线治疗应遵循国家治疗指南。结论：高危人群中H．pylori筛查和根除策略可能会减少胃癌的发生率，本共识根据现有证据予以推荐。     

根除幽门螺杆菌是降低胃癌发病率的必由之路

胃癌目前已成为全球第四常见的恶性肿瘤,在全球恶性肿瘤致死原因中位居第二位。幽门螺杆菌感染是胃癌发生发展的主要危险因素之一。在胃癌的多阶段发病机制中,幽门螺杆菌感染缓慢诱导慢性活动性胃炎的发生,并经过萎缩性胃炎、肠上皮化生、异型增生等癌前阶段,最终发展为胃癌。相关研究证明根除幽门螺杆菌,特别是在早期阶段,能够有效预防胃癌的发生,并且通过根除幽门螺杆菌可阻止一部分胃癌前病变的发展并使其逆转。文章就根除幽门螺杆菌在胃癌预防中的作用进行总结。     

中国自然人群筛查与伺机性检测策略预防幽门螺杆菌相关疾病的卫生经济学评价

目的:对 H.pylori自然人群筛查和伺机性检测策略用于预防 H.pylori相关疾病进行卫生经济学评价。 方法:建立 H.pylori感染、非溃疡性消化不良、消化性溃疡(PU)、胃癌等状态的马尔可夫模型,模拟计算在我国10万自然人群中实施自然人群筛查、伺机性检测和无干预...     

新序贯疗法治疗幽门螺杆菌阳性萎缩性胃炎的临床应用价值研究

萎缩性胃炎与胃癌存在一定关系,而幽门螺杆菌（Hp）感染与萎缩性胃炎的发生和发展存在密切联系[1],根除幽门螺杆菌是治疗萎缩性胃炎的重要措施.随着幽门螺杆菌耐药性的增加,传统三联抗幽门螺杆菌治疗的有效率逐步下降[2].我们采用新序贯疗法治疗Hp阳性的萎缩性胃炎患者,并与传统三联疗法治疗进行比较.     

用卫生经济学观点看筛查并根除幽门螺杆菌预防胃癌

胃癌在我国恶性肿瘤中的发病率和死亡率均较高。幽门螺杆菌(Hp)感染在胃黏膜炎症、萎缩和肠化生中起重要作用,大量流行病学研究证据显示,Hp感染与胃癌发病呈正相关。目前,我国人群Hp现症感染率接近50%,根除Hp可降低胃癌发生风险,并具有成本效果优势,但筛查并根除Hp在我国应用并不广泛。本文从卫生经济学角度阐述Hp筛查与根除在胃癌预防中的作用,并分析影响这一决策实施的关键因素。     

中国自然人群筛查与伺机性检测策略预防幽门螺杆菌相关疾病的卫生经济学评价

目的对H.pylori自然人群筛查和伺机性检测策略用于预防H.pylori相关疾病进行卫生经济学评价。方法建立H.pylori感染、非溃疡性消化不良、消化性溃疡(PU)、胃癌等状态的马尔可夫模型,模拟计算在我国10万自然人群中实施自然人群筛查、伺机性检测和无干预策略的成本和效果,对自然人群筛查和伺机性检测策略进行卫生经济学评价。统计学方法采用Wilcoxon符号秩检验。采用单因素敏感性分析单个参数不确定性对成本-效果的影响,采用概率敏感性分析所有参数的共同不确定性对成本-效果的影响。结果与伺机性检测策略和无干预策略相比,自然人群筛查策略的总成本分别减少了0.43百万元(-6.63百万元,7.19百万元)和4.45百万元(-8.60百万元,27.93百万元),质量调整生命年(QALY)生命年和无症状月分别延长了888.00个(479.86个,1 574.10个)和3 032.78个(1 756.04个,5 007.84个)、651.82个(294.73个,1 211.94个)和1 868.64个(1 045.88个,3 148.34个)、28 381.91个(19 109.54个,43 ...     

幽门螺杆菌感染与胃粘膜上皮细胞增殖和凋亡

幽门螺杆菌感染与胃粘膜上皮细胞增殖和凋亡萧树东刘文忠流行病学调查表明，胃癌发病率与当地的幽门螺杆菌（Ｈｐ）感染率呈正相关，Ｈｐ感染者发生胃癌的危险性较非感染者高６倍［１］。从慢性浅表性胃炎、萎缩性胃炎、肠上皮化生及异型增生到胃癌的演变过程已经明确。Ｈ...     

幽门螺杆菌感染胃癌组织MMP-2和MMP-9表达及其对胃癌侵袭转移能力的影响

目的:分析幽门螺杆菌感染对胃癌转移侵袭能力的影响,同时对其基质金属蛋白酶2(MMP-2)和基质金属蛋白酶9(MMP-9)表达情况进行检测.方法:采用改良的Giemsa法检测幽门螺杆菌感染,免疫组化法检测42例胃癌标本MMP-9和MMP-2表达情况.采用Fisher's exact检验对幽门螺杆菌感染和胃癌患者临床病理特征的相关性进行分析.结果:胃癌组织中幽门螺杆菌感染率为61.9%(26/42).幽门螺杆菌感染与胃癌的分期和淋巴结转移状况相关,与患者性别、发病年龄、及组织类型无相关性.幽门螺杆菌感染与MMP-9和MMP-2表达均具有相关性(χ2=7.77,P<0.01;χ2=8.08,P<0.01).结论:幽门螺杆菌感染能够增加胃癌的侵袭转移能力,其机制可能与MMP-9和MMP-2表达增加有关.     

Cost effectiveness analysis of population-based serology screening and ^13C-Urea breath test for Helicobacter pylori to prevent gastric cancer： A markov model

AIM：To compare the costs and effectiveness of no screening and no eradication therapy, the populationbased Helicobacter pylori （H pylori） serology screening with eradication therapy and 13C-Urea breath test （UBT） with eradication therapy.
METHODS：A Markov model simulation was carried out in all 237 900 Chinese males with age between 35 and 44 from the perspective of the public healthcare provider in Singapore. The main outcome measures were the costs, number of gastric cancer cases prevented, life years saved, and quality-adjusted life years （QALYs） gained from screening age to death. The uncertainty surrounding the cost-effectiveness ratio was addressed by one-way sensitivity analyses.
RESULTS：Compared to no screening, the incremental cost-effectiveness ratio （ICER） was $16 166 per life year saved or $13 571 per QALY gained for the serology screening, and $38 792 per life year saved and $32 525 per QALY gained for the UBT. The ICER was $477 079 per life year saved or $390 337 per QALY gained for the UBT compared to the serology screening. The costeffectiveness of serology screening over the UBT was robust to most parameters in the model. CONCLUSION：The population-based serologyscreening for H pylori was more cost-effective than the UBT in prevention of gastric cancer in Singapore Chinese males.     

Treatment of Helicobacter pylori infection to reduce gastric cancer incidence: Uncertain benefits of a community based programme in Australia

Helicobacter pylori is a cause of gastric adenocarcinoma, but the role of H. pylori eradication in reducing cancer risk is unknown. We sought to estimate the benefits of a screening and treatment programme for H. pylori infection, aimed at reducing the incidence of gastric cancer in Australia. The impact of this programme on cancer incidence was evaluated in sensitivity analyses utilizing Western Australian Cancer Registry data and published data on the epidemiology of H. pylori and gastric cancer. The impact of variation in parameters used in the sensitivity analyses was substantial, ranging from a 38% reduction in lifetime risk of gastric cancer in a best-case to 3% in a worst-case scenario. In an intermediate-case scenario there is a 23% reduction in lifetime risk, but in real terms this reflects a fall in cumulative incidence from 0.7 to 0.5% for males or 0.3 to 0.2% for females. The projected cumulative lifetime incidence of gastric cancer in H. pylori -infected males is 2.2% and 0.9% for females; this contrasts with 0.4 and 0.2%, respectively, for those never infected. According to an intermediate-case scenario, to prevent one gastric cancer, screening with or without subsequent treatment would be required in 617 men or 1639 women. Furthermore, this programme may be less effective in reducing cancer incidence than would be achieved naturally over the next 15 years, providing the current annual decline in gastric cancer incidence continues. In conclusion, the benefits of a community based programme of H. pylori eradication in terms of cancer risk reduction remain unclear, related largely to uncertainties in the parameters used to calculate these benefits. In Australia, any benefits obtained are likely to be, at best, modest.     

Characteristics of gastric cancer in peptic ulcer patients with Helicobacter pylori infection

AIM:To evaluate the incidence and clinical characteristics of gastric cancer(GC) in peptic ulcer patients with Helicobacter pylori(H.pylori) infection.METHODS:Between January 2003 and December 2013, the medical records of patients diagnosed with GC were retrospectively reviewed.Those with previous gastric ulcer(GU) and H.pylori infection were assigned to the Hp GU-GC group(n = 86) and those with previous duodenal ulcer(DU) disease and H.pylori infection were assigned to the Hp DUGC group(n = 35).The incidence rates of GC in the Hp GU-GC and Hp DU-GC groups were analyzed.Data on demographics(age, gender, peptic ulcer complications and cancer treatment), GC clinical characteristics [location, pathological diagnosis, differentiation, T stage, Lauren's classification, atrophy of surrounding mucosa and intestinal metaplasia(IM)], outcome of eradication therapy for H.pylori infection, esophagogastroduodenoscopy number and the duration until GC onset were reviewed.Univariate and multivariate analyses were performed to identify factors influencing GC development.The relative risk of GC was evaluated using a Cox proportional hazards model.RESULTS:The incidence rates of GC were 3.60%(86/2387) in the Hp GU-GC group and 1.66%(35/2098) in the Hp DU-GC group.The annual incidence was 0.41% in the Hp GU-GC group and 0.11% in the Hp DUGC group.The rates of moderate-to-severe atrophy of the surrounding mucosa and IM were higher in the Hp GU-GC group than in the Hp DU-GC group(86% vs 34.3%, respectively, and 61.6% vs 14.3%, respectively, P 0.05).In the univariate analysis, atrophy of surrounding mucosa, IM and eradication therapy for H.pylori infection were significantly associated with the development of GC(P 0.05).There was no significant difference in the prognosis of GC patients between the Hp GU-GC and Hp DU-GC groups(P = 0.347).The relative risk of GC development in the Hp GUGC group compared to that of the Hp DU-GC group,after correction for age and gender,was 1.71(95%CI:1.09-2.70;P=0.02).CONCLUSION:GU patients with H.pylori infection had higher GC incidence rates and relative risks.Atrophy of surrounding mucosa,IM and eradication therapy were associated with GC.     

化工人群幽门螺杆菌感染与胃癌关系的探讨

目的 通过：（１）幽门螺杆菌（ＨＰ）感染的流行病学调查;（２）ＨＰ感染与胃癌前病变的关系;（３）ＨＰ在胃窦癌中的检出率三个方面来评价ＨＰ感染与胃癌的相关性。方法 分别为：（１）随机对南化公司２８４１名健康工人的血清作ＨＰ抗体测定;（２）将胃镜检查的６４８例作ＨＰ检测和病理组织学检查;（３）对５０例胃窦腺癌病理组织学切片鉴定基ＨＰ检出率。结果 化工人群ＨＰ感染率６１．０４％,显著高于本省对照人群（３     

The cost-effectiveness of low-dose CT screening for lung cancer: preliminary results of baseline screening

BACKGROUND: Low-dose CT scan screening greatly improves the likelihood of detecting small nodules and, thus, of detecting lung cancer at a potentially more curable stage. METHODS: To evaluate the cost-effectiveness of a single baseline low-dose CT scan for lung cancer screening in high-risk individuals, data from the Early Lung Cancer Action Project (ELCAP) was incorporated into a decision analysis model comparing low-dose CT scan screening of high-risk individuals (ie, those > or = 60 years with at least 10 pack-years of cigarette smoking and no other malignancies) to observation without screening. Cost-effectiveness was expressed as the incremental cost per year of life saved. The analysis adopted the perspectives of the health-care system. The probability of the different outcomes following the decision either to screen or not to screen an individual at risk was based on data from ELCAP and the Surveillance, Epidemiology, and End Results Registry or published data, respectively. The cost of the screening and treatment of patients with lung cancer was established based on data from the New York Presbyterian Hospital's financial system. The base-case analysis was conducted under the assumption of similar aggressiveness of screen-detected and incidentally discovered lung cancers and then was followed by multiple sensitivity analyses to relax these assumptions. RESULTS: The incremental cost-effectiveness ratio of a single baseline low-dose CT scan was 2,500 US dollars per year of life saved. The base-case analysis showed that screening would be expected to increase survival by 0.1 year at an incremental cost of approximately 230 US dollars. Only when the likelihood of overdiagnosis was > 50% did the cost effectiveness ratio exceed 50,000 US dollars per year of life saved. The cost-effectiveness ratios were also relatively insensitive to estimates of the potential lead-time bias. CONCLUSIONS: A baseline low-dose CT scan for lung cancer screening is potentially highly cost-effective and compares favorably to the cost-effectiveness ratios of other screening programs.     

老年人胃癌与谷胱甘肽转硫酶P1基因多态性关系的研究

目的 探讨幽门螺杆菌(Hp)感染及谷胱甘肽转硫酶P1(GSTP1)基因多态性与胃癌的关系.方法 选择老年胃癌患者(胃癌组)98例和胃镜检查正常者(对照组)149例,以快速尿素酶试验、13C-尿素呼气试验或活检标本吉姆萨染色(Giemsa)检测Hp感染;通过聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)分析方法检测GSTP1基因型.结果 Hp感染率胃癌组(54.1%)与对照组(40.9%)比较,差异有统计学意义(x2=4.11,P＜0.05);具有GSTP1突变纯和基因型并有Hp感染阳性的人群胃癌发病风险显著增加OR值5.44(1.26～26.79)(x2=7.13,P＜0.01).结论 老年患者Hp感染和GSTP1基因型多态性与胃癌的发病风险有关.

Abstract：

Objective To study the relationships of Helicobacter pylori (Hp) infection and genetic polymorphisms of glutathione s-transferase P1 (GSTP1) with gastric cancer (GC). Methods The 98 patients with GC and 149 controls with normal finding at endoscopy were enrolled for this study. The rapid urease test (RUT), 13C- urea breath test (13C-UBT) and Giemsa staining of biopsy samples were used to check Hp infection. PCR-based restriction fragment length polymorphisms (PCR-RFLP) was used to detect GSTP1 genotype. Results The rate of Hp infection was higher in GC group than in control group (54.1% vs. 40.9%, x2 =4.11, P＜0. 05). The risk of GC would significantly increase in the GSTP1 homozygous mutant gene (MM) group with Hp infection (OR=5.44, 95%CI 1. 26-26. 79, x2=7.13, P＜0.05). Conclusions Hp infection and GSTP1 genetic polymorphisms are associated with gastric cancer risk in the elderly.     

幽门螺杆菌与胃癌的关系

本文报道1994年在福建长乐进行的大规模胃癌防治计划,通过胃镜、血液检查及问卷检查,发现30例胃癌及214例消化性溃疡,幽门螺杆菌的感染率在各类人群中为67％至94％不等。在年龄36岁至65岁组中,长乐地区幽门螺杆菌的感染率明显高于香港,无论是幽门螺杆菌的感染者或非感染者,胃窦肠上皮化生发现率在长乐都高于香港,在长乐,胃窦肠上皮化生发现率高于胃体肠上皮化生。长乐及香港的Cag-A阳性菌株与各种胃疾病有明显关系,在无症状组中,Cag-A阳性菌株在长乐占72％,明显高于香港的29％。Cag-A阳性菌株与胃炎、粘膜萎缩、肠上皮化生、不典型增生和胃癌有明显关系。问卷发现多喝茶及多进食蔬菜有保护作用,而抽烟及饮酒人群或进食咸鱼有较多机会形成胃癌。     

Endoscopic screening for gastric cancer.

BACKGROUND & AIMS: Population endoscopic screening for gastric cancer is generally deemed not to be cost-effective except in Japan, where its prevalence is very high. However, in the absence of screening, patients present with advanced disease, and prognosis is poor. We conducted a cost utility analysis to determine whether endoscopic screening for stomach cancer in intermediate-risk population would be cost-effective and to better define the high-risk groups in the population who would benefit from such strategy. METHODS: Cost-effectiveness analysis was performed by using a Markov Model. Simulation was performed on Singapore (intermediate-risk) population and various high-risk subgroups. Comparison was made between 2-yearly endoscopic mass screening program versus no screening. Data sources were extracted from relevant studies published from 1980-2004 identified via systematic PUBMED search. Main outcome measures were deaths caused by stomach cancer averted, cost per life saved, and incremental cost-effectiveness ratio expressed as cost per quality-adjusted life year (QALY) saved. RESULTS: Screening of high-risk group of Chinese men (age-standardized rate, 25.9/100,000) from 50-70 years old is highly cost-effective, with cost benefit of United States $26,836 per QALY. Screening this cohort of 199,000 subjects prevents 743 stomach cancer deaths and saves 8234 absolute life years. Cost of averting 1 cancer death is United States $247,600. Cost-effectiveness was most sensitive to incidence of stomach cancer and cost of screening endoscopy. CONCLUSIONS: Screening of stomach cancer in moderate to high-risk population subgroups is cost-effective. Targeted screening strategies for stomach cancer should be explored.     

Treatment of Helicobacter pylori infection in atrophic gastritis

Helicobacter pylori(Hp) is a major human pathogen causing chronic, progressive gastric mucosal damage and is linked to gastric atrophy and cancer. Hp-positive individuals constitute the major reservoir for transmission of infection. There is no ideal treatment for Hp. Hp infection is not cured by a single antibiotic, and sometimes, a combined treatment with three or more antibiotics is ineffective. Atrophic gastritis(AG) is a chronic disease whose main features are atrophy and/or intestinal metaplasia of the gastric glands, which arise from long-standing Hp infection. AG is reportedly linked to an increased risk for gastric cancer, particularly when extensive intestinal metaplasia is present. Active or past Hp infection may be detected by conventional methods in about two-thirds of AG patients. By immunoblotting of sera against Hp whole-cell protein lysates, a previous exposure to Hp infection is detected in all AG patients. According to guidelines, AG patients with Hp positivity should receive eradication treatment. The goals of treatment are as follows:(1) Cure of infection, resolution of inflammation and normalization of gastric functions;(2) possible reversal of atrophic and metaplastic changes of the gastric mucosa; and(3) prevention of gastric cancer. An ideal antibiotic regimen for Hp should achieve eradication rates of approximately 90%, and complex multidrug regimens are required to reach this goal. Amongst the factors associated with treatment failure are high bacterial load, high gastric acidity, Hp strain, smoking, low compliance, overweight, and increasing antibiotic resistance. AG, when involving the corporal mucosa, is linked to reduced gastric acid secretion. At a non-acidic intra-gastric p H, the efficacy of the common treatment regimens combining proton pump inhibitors with one or more antibiotics may not be the same as that observed in patients with Hp gastritis in an acid-producing stomach. Although the efficacy of these therapeutic regimens has been thoroughly tested in subjects with Hp infection, there is a paucity of evidence in the subgroupof patients with AG. Bismuth-based therapy may be an attractive treatment in the specific setting of AG, and specific studies on the efficacy of bismuth-based therapies are needed in patients with AG.     

Will treatment of Helicobacter pylori infection in childhood alter the risk of developing gastric cancer?

Helicobacter pylori has been classified as a group 1 carcinogen for gastric cancer. It is estimated that there is between a two- and sixfold increase in the risk of developing gastric cancer among infected patients. Among different populations, the risk of H. pylori-infected individuals developing gastric cancer varies greatly. However, on a worldwide scale, gastric cancer is the second most common cause of cancer-related death. Therefore, H. pylori eradication could help prevent up to three to four million gastric cancer deaths per year. H. pylori is usually acquired in childhood. Because infected children have not harboured the organism for long enough to have developed precancerous lesions, childhood is theoretically an attractive time for H. pylori eradication and, thus, could help prevent gastric cancer later in life. However, as H. pylori prevalence and the incidence of gastric cancer are falling rapidly in developed nations, widespread population screening programs aimed at the eradication of H. pylori in these countries would be enormously expensive. Therefore, except in groups with a high risk for development of gastric cancer (eg, Japanese or those with a strong positive family history of gastric cancer), a population-based test-and-treat policy is not justified.