幽门螺杆菌根除治疗在胃癌预防中的现状及前景

幽门螺杆菌(Helicobacter pylori,H.pylori)与胃癌(gastric cancer,GC)发生发展密切相关,根除H.pylori可降低GC发生率.经济学分析表明,在高危人群中根除治疗H.pylori作为预防GC的策略是成本效益较好的.即使在GC低风险人群中,H.pylori筛查和治疗也能使上消化道其他非恶性疾病获益.然而,广泛开展H.pylori根除治疗可能带来其他问题,包括抗生素耐药增加和与H.pylori负相关疾病(如胃食管反流病、Barrett食管、哮喘和肥胖等)的患病率升高.本文将结合近年最新研究,就上述问题展开论述,进一步提出H.pylori根除治疗预防GC所面临的挑战以及将来可能的进展方向.     

幽门螺杆菌根除效果的影响因素分析

幽门螺杆菌(Helicobacter pylori,H.pylori)感染是最常见的细菌感染之一,影响着世界约50%的人口,被世界卫生组织定义为胃癌致病因子。H.pylori根除治疗可以降低消化性溃疡、胃癌等疾病的发病风险。目前H.pylori根除率呈逐渐下降的趋势。加深对其根除率影响因素的了解,可能有助于制定更为有效的根除治疗或预防感染的方案。本文结合国内外相关研究,对影响H.pylori根除率的因素作一概述。     

乳铁蛋白抗幽门螺杆菌感染研究进展

幽门螺杆菌（H.pylori）感染与慢性胃炎、消化性溃疡、胃癌、胃黏膜相关淋巴组织（MALT）淋巴瘤等疾病的发生密切相关．寻找安全、有效、价廉、使用便捷的抗H.pylori治疗方案是当前研究的热点。近年研究表明乳铁蛋白（lactoferrin。LF）具有抗H.pylori的作用，可提高H.pylori一线根除方案的根除率。本文就LF的分子特性、生物学作用及其抗H.pylori的作用和机制作一综述。     

第六届上海国际胃肠病学大会会议纪要（二）

三、消化系肿瘤 1．胃癌：德国Peter Malfertheiner教授在分析胃腺癌预防的可行性时指出，H．pylori是胃癌发生的主要危险因素之一。目前的一个关键命题是关于“不可逆点”，即在胃黏膜已经发生癌前病变的情况下，即使根除了H.pylori，病变也不会逆转，甚至继续进展。所以即使根除H．pylori也无法通过现有指标确定患者是否有罹患胃癌的风险。部分萎缩性胃炎和肠化生患者病变有进展可能，目前需要一项或一系列指标对常规组织学检测进行补充以评估和预测病变进展情况。对有“进展”倾向的胃炎患者（萎缩、肠化生），     

幽门螺杆菌根除治疗、治疗失败的原因及其对策

幽门螺杆菌(H.pylri)感染已被证明是慢性胃炎和消化性溃疡的主要致病因子,并在胃癌发生的初始阶段起重要作用[1].在我国,60%以上的人群有H.pylori感染,根除H.pylori感染可治愈胃炎和消化性溃疡,且可预防胃癌的发生[1,2].目前已有几种有效的H.pylori根除治疗方案,有些治疗方案具有多重药物、剂量大、疗程长、副作用多和可能产生耐药性等缺点,而另一些较新的治疗方案虽可克服以上缺点,但却存在治疗费用高等问题.本文将详细介绍当前推荐的H.pylori根除治疗的一线、二线治疗方案,以及治疗失败的原因和对策.     

胃癌和幽门螺杆菌研究进展

在世界上肿瘤致死的原因中胃癌居第二位,早期诊断是唯一可能降低死亡率的途径。筛查胃癌高危人群以期早期诊断,识别胃癌的危险因素也一直是实施干预策略的主要目标。尽管已确认幽门螺杆菌（Hpylori）感染与胃癌密切相关,但根除H．pylori治疗是否能预防胃癌还需更有力的证据来证明。本文就第六届上海国际胃肠病学会议期间欧美和亚太地区专家对亚太地区胃癌以及H．pylori与胃癌关系研究的专题报告进行总结并加以补充。     

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。     

胃癌的化学预防

当前对胃癌化学预防的研究主要集中在根除幽门螺杆菌(H.pylori)﹑抗氧化剂﹑叶酸、选择性环氧合酶(COX)-2抑制剂上。动物实验和临床研究均发现,根除H.pylori能够预防胃癌的发生,在癌前病变形成前根除效果更佳。某些抗氧化剂(β-胡萝卜素、维生素A、C、E,绿茶、硒等)和叶酸通过保护DNA免受氧化损害和提高DNA甲基化水平预防胃癌的发生。选择性COX-2抑制剂在动物实验中能显著降低胃癌发生率和癌前病变发生率,目前已正式用于肿瘤的预防,其预防效果有待于大规模临床研究。     

重视幽门螺杆菌耐药菌株的研究

幽门螺杆菌（H．pylori）的发现使慢性胃炎和消化性溃疡的病因学和治疗学发生了重大变革，H．pylori感染与慢性胃炎、消化性溃疡、胃癌以及胃黏膜相关淋巴组织（MALT）淋巴瘤密切相关已得到公认。因此，H．pylori感染的治疗已成为目前H．pylori研究领域的重点课题，也是临床医师最为关注的问题之一。在H．pylori感染的治疗中．细菌对抗生素产生耐药是导致根除治疗失败的主要原因，因此H．pylori耐药菌株的研究已引起人们的普遍关注。     

解读和评述:中国慢性胃炎共识意见

中华医学会消化病学分会于2006年9月14～16日在上海召开了第二届全国慢性胃炎共识会议。自2000年全国慢性胃炎研讨会在江西召开以来，慢性胃炎的研究在以下各方面均取得了一定进展，包括萎缩性胃炎的内镜和组织病理学诊断，幽门螺杆菌（H．pylori）感染与萎缩性胃炎及其演变成胃癌的关系，根除H．pylori对胃癌的预防作用，环境因素、尤其是生物活性食物成分对萎缩性胃炎和胃癌发生、发展的预防作用等。本文对第二届全国慢性胃炎共识意见作一解读和评述。     

Treatment of Helicobacter pylori and prevention of gastric cancer

Gastric cancer is the second commonest fatal malignancy in the world with a high incidence in China. Helicobacter pylori infection is an important factor in the pathogenesis of gastric cancer. Epidemiological studies have shown a strong causal relationship between H. pylori infection and gastric cancer. Animal studies also show that eradication of H. pylori infection, especially at the early stage, is effective in preventing H. pylori-related gastric carcinogenesis. H. pylori eradication leads to regression and prevents the progression of gastric precancerous lesions, but only in a minority of cases. H. pylori eradication appears to be the most promising approach in gastric cancer prevention. The current available data in human studies showed that H. pylori eradication can reduce the risk of developing gastric cancer and this strategy is more useful in patients without atrophic gastritis or intestinal metaplasia. A longer follow-up and additional studies are needed for better understanding this issue.     

Characteristics and predictors of gastric cancer after Helicobacter pylori eradication

Helicobacter pylori(H. pylori) eradication can reduce gastric cancer. However, gastric cancer still develops after eradication, and cases who received eradication therapy are increasing. In this study, we have reviewed the characteristics and predictors of primary gastric cancer developing after H. pylori eradication. In terms of the characteristics, endoscopic, histologic, and molecular characteristics are reported. Endoscopically, gastric cancer after eradication is often depressedtype and shows a gastritis-like appearance, which sometimes makes the diagnosis difficult. Histologically, most gastric cancer after eradication is intestinal type, and non-neoplastic epithelium, also called epithelium with low-grade atypia, is frequently seen over the tumor, which is presumably the cause of the endoscopic gastritis-like appearance. As for molecular characteristics, some markers, such as Ki67, MUC2, and Wnt5a expression, are lower in cancer from patients in whom H. pylori has been eradicated. In terms of predictors, several Japanese studies have reported that severe endoscopic atrophy at eradication is a risk factor for gastric cancer development. Histologic intestinal metaplasia, especially in the corpus, and long-term use of proton pump inhibitors, are also reported as risk factors for gastric cancer after H. pylori eradication. These studies on the characteristics and predictors of gastric cancer development will become the cornerstone for establishing a novel surveillance program based on the gastric cancer risk stratification specific to H. pylori-eradicated patients.     

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.     

Eradication of H pylori for the prevention of gastric cancer

Infection with H pylori is the most important known etiological factor associated with gastric cancer. While colonization of the gastric mucosa with H pylori results in active and chronic gastritis in virtually all individuals infected, the likelihood of developing gastric cancer depends on environmental, bacterial virulence and host specific factors. The majority of all gastric cancer cases are attributable to H pylori infection and therefore theoretically preventable. There is evidence from animal models that eradication of H pylori at an early time point can prevent gastric cancer development. However, randomized clinical trials exploring the prophylactic effect of H pylori eradication on the incidence of gastric cancer in humans remain sparse and have yielded conflicting results. Better markers for the identification of patients at risk for H pylori induced gastric malignancy are needed to allow the development of a more efficient public eradication strategy. Meanwhile, screening and treatment of H pylori in first-degree relatives of gastric cancer patients as well as certain high-risk populations might be beneficial.     

Effect of Helicobacter pylori eradication on subsequent development of cancer after endoscopic resection of early gastric cancer in Japan

This article describes the characteristics of H. pylori infection dynamics in early gastric cancer cases in Japan and the reduced likelihood of metachronous cancer development and growth inhibition by H. pylori eradication based on healing of background gastric mucosa. In the future, these clinical studies and experimental studies in Mongolian gerbils and mice should elucidate the role of H. pylori infection in the development of gastric carcinogenesis to clinical cancer on the genetic level so that gastric cancer prevention by H. pylori eradication is established.     

Endoscopic surveillance of gastric cancers after Helicobacter pylori eradication

The incidence and mortality of gastric cancer remains high in East Asian countries. Current data suggest that Helicobacter pylori(H. pylori) eradication might be more effective for preventing gastric cancer in young people before they develop atrophic gastritis and intestinal metaplasia. However, the long-term effect of H. pylori eradication on metachronous cancer prevention after endoscopic resection(ER) of early gastric cancer remains controversial, with some discordance between results published for Japanese and Korean studies.The detection ability of synchronous lesions before ER and eradication of H. pylori directly influences these results. After eradication, some gastric cancers are more difficult to diagnose by endoscopy because of morphologic changes that lead to a flat or depressed appearance. Narrow-band imaging with magnifying endoscopy(NBI-ME) is expected to be useful for identifying metachronous cancers. However, some gastric cancers after eradication show a "gastritislike"appearance under NBI-ME. The gastritis-like appearance correlates with the histological surface differentiation of the cancer tubules and superficial non-neoplastic epithelium atop or interspersed with the cancer. Till date, it remains unclear whether H.pylori eradication could prevent progression of gastric cancer. Until we can establish more useful endoscopic examination methodologies, regular endoscopic surveillance of high-risk groups is expected to be the most beneficial approach for detection.     

The effect of eradicating helicobacter pylori on the development of gastric cancer in patients with peptic ulcer disease

OBJECTIVES: Infection with Helicobacter pylori is a risk factor for the development of gastric cancer. However, it is not known whether eradication therapy can prevent the development of gastric cancer in persons in whom the cancer is not yet established. In the present study, we investigated whether the eradication of H. pylori in patients with peptic ulcer disease reduces the likelihood of their developing gastric cancer. METHODS: Prospective posteradication evaluations were conducted in 1,342 consecutive patients (1,191 men and 151 women; mean age: 50 yr) with peptic ulcer diseases who had received H. pylori eradication therapy. After confirmation of eradication, endoscopy and a urea breath test were performed yearly. RESULTS: A total of 1,120 patients completed more than 1-yr follow-up and were followed for up to 8.6 yr (a mean of 3.4 yr). Gastric cancer developed in 8 of 944 patients cured of infection and 4 of 176 who had persistent infection (p= 0.04; log-rank test). All the gastric cancer developed in patients with gastric ulcer, but none in patients with duodenal ulcer (p= 0.005; Fisher's exact test). In patients with gastric ulcer, persistent infection was identified as a significant factor for the risk of developing gastric cancer (hazard ratio: 3.35; 95% confidence interval: 1.00-11.22; p= 0.04; Cox's proportional-hazards model). CONCLUSION: H. pylori eradication may reduce their risk of developing gastric cancer in patients with gastric ulcer. Large-scale studies in additional populations of this important international public-health issue are warranted.     

Can gastric cancer be prevented by Helicobacter pylori eradication?

Helicobacter pylori infection always causes chronic gastritis and triggers several gastroduodenal pathologies ranging from peptic ulcer disease to gastric cancer. It is well established that H. pylori eradication decreases the incidence of gastroduodenal ulcer and its recurrence. However, despite being accepted as the critical risk factor for gastric cancer, there is no conclusive evidence that H. pylori eradication decreases the incidence of gastric cancer. Bacterial virulence characteristics, as well as genetic predisposition of the host in conjunction with certain environmental conditions, are the major factors which influence the development of gastric cancer. Preclinical and clinical data suggest that reversibility of precancerous lesions (atrophic gastritis and intestinal metaplasia) is possible in some patients after H. pylori eradication. Since neoplastic lesions do not progress - or even regress in some cases - after H. pylori eradication, eradication therapy should be considered even in patients with precancerous lesions. Nonetheless, progression of atrophic gastritis and intestinal metaplasia into cancer has been also demonstrated in patients after H. pylori eradication, suggesting that there might be a point of no return where genetic changes have already happened and are irreversible despite elimination of the triggering carcinogen (H. pylori). At the present time the clinical decision to treat a patient is based on established risk profiles. A general screen-and-treat policy, although desirable, currently awaits a less complex treatment regimen.     

Prevention of gastric cancer: a challenging but feasible task

Despite its declining incidence gastric cancer still ranks as the second most common malignancy of the digestive tract, accounting for 10% of cancer deaths worldwide. At the time of the diagnosis less than 15% of the patients are in the stage of early cancer, the only stage in which a definite cure of gastric cancer is possible. Therefore the challenges are either early detection or even better prevention of gastric cancer. H. pylori has become recognized as the major risk factor for gastric adenocarcinoma. Epidemiological, biological, histomorphologic, molecular-genetic, epidemiological evidence and more recently few clinical trails have shown that H. pylori eradication has the potential to prevent the development of gastric cancer. Currently H. pylori eradication is an indication for the prevention of gastric cancer in patients and groups of individuals with strongly increased risk, but further investigations are still required before an implementation of a general and global policy to eradicate H. pylori for the prevention of gastric cancer can be instituted. At present time, the main challenge remains to find out at what point mucosal abnormalities are no longer reversible and gastric cancer development cannot be prevented despite H. pylori eradication.     

Prevention of gastric cancer by Helicobacter pylori eradication

The evidence supporting the important role of Helicobacter pylori causing gastric cancer is getting stronger. The mechanisms by which H. pylori can influence the progression to severe changes in the gastric mucosa are under investigation. An increased gastric epithelial cell proliferation has been observed in individuals infected with H. pylori. This lifelong increased cell turnover is deemed to be a major risk factor for increased mutational changes and may lead to the development of gastric cancer. Successful eradication of H. pylori infection induces the healing of the gastritis and a significant decrease in gastric epithelial cell proliferation. Nevertheless, it is right now unknown at which time the point of no return, meaning at which time an eradication therapy leads to a benefit for the individual to prevent gastric cancer, has been reached. Therefore the major question that arises is to whom an eradication therapy should be offered to prevent gastric cancer. A general elimination of the infection might be worthwhile, but seems to be unrealistic now because of the high prevalence of the infection and the missing of a vaccine. This review reflects possible mechanisms of gastric cancer development induced by chronic H. pylori infection and recent investigational trials for prevention of gastric cancer by H. pylori eradication therapy will be discussed.