1、幽门螺杆菌而非胃泌素与结肠瘤变的发生相关
Helicobacter pylori but not gastrin is associated with the development of colonic neoplasms
Selgrad M Bornschein J, Kandulski A, Hille C, Weigt J, Roessner A, Wex T, Malfertheiner P.
Int J Cancer. 2014 Sep 1;135(5):1127-31. Epub 2014 Feb 11.
Abstract
Recent studies have suggested that Helicobacter pylori (H. pylori) constitutes a risk for the development of colonic neoplasia. Hypergastrinemia can be induced by H. pylori infection, and gastrin can act as putative promoter of colorectal carcinogenesis. Aim of our study was to assess whether H. pylori infection and/or increased serum gastrin levels are associated with the occurrence of colonic neoplasms. For this, we reviewed prospectively collected data of 377 patients with a minimum age of 50 years who underwent colonoscopy. H. pylori and CagA status were determined by serology. Serum gastrin levels were measured in fasting state by commercially available assay. In H. pylori infected patients (n = 138; 36.6%), the overall prevalence of colonic neoplasms was more frequent compared to H. pylori negative patients (n = 239; 63.4%) (OR = 2.73, 95% CI: 1.76-4.24). H. pylori infection occurred more frequently in patients with hyperplastic polyps (OR = 2.66, 95% CI: 1.23-5.74) and adenomas presenting with low grade intraepithelial neoplasia (IEN) (OR = 1.85, 95% CI: 1.14-2.99). Attributable risk for adenomas with high grade IEN and colorectal adenocarcinoma (n = 14) was not assessed due to the low number of cases. The expression of CagA was also associated with an increased risk for colonic neoplasms (OR = 2.25, 95% CI: 1.29-3.94). Hypergastrinemia did not increase the risk for any colonic neoplasms and there was no difference in basal serum gastrin levels between H. pylori positive and negative patients. In conclusion, H. pylori infection, including CagA expression is associated with an increased risk for the development of colonic neoplasm.
近期研究表明幽门螺杆菌是结肠瘤变发生的一个危险因素。幽门螺杆菌感染能够导致高胃泌素血症，而胃泌素是结直肠癌的假定致癌因素。因此，本研究的目的在于评估幽门螺杆菌和或升高的血清胃泌素水平是否与结肠瘤变的发生相关。我们分析了前瞻性收集的377例年龄在50岁以上行结肠镜检查的患者资料。幽门螺杆菌和毒力因子CagA通过血清学方法来检测，血清胃泌素水平在患者空腹状态下由现用方法测定。结果显示：在幽门螺杆菌感染阳性患者中（n=138；36.6%）结肠瘤变的总患病频率高于幽门螺杆菌感染的阴性患者（n=239;63.4%）（OR=2.73,95CI：1.76-4.24）。幽门螺杆菌感染更易见于增生性息肉（OR = 2.66, 95% CI: 1.23-5.74）和低级别上皮内瘤变腺瘤的患者（OR = 1.85, 95% CI: 1.14-2.99）。而由于高级别上皮内瘤变腺瘤和结直肠癌患者的人数较少（n=14），未对幽门螺杆菌的致癌风险做评估。此外，毒力因子CagA的表达也与结肠肿瘤的发病风险相关（OR = 2.25, 95% CI: 1.29-3.94）。高胃泌素血症未能增加结肠肿瘤的发病风险，并且在幽门螺杆菌感染阳性和阴性患者中胃泌素基础水平未显示出差异。总之，本文通过研究发现幽门螺杆菌感染及CagA表达水平与结肠肿瘤发生风险相关联。
2、白细胞介素17基因多态性及其与幽门螺杆菌感染交互作用与胃癌发病风险的关联研究——来自中国人群的证据
Analysis of the association of interleukin-17 gene polymorphisms with gastric cancer risk and interaction with Helicobacter pylori infection in a Chinese population.
Zhang X1, Zheng L, Sun Y, Zhang X.
Tumour Biol. 2014 Feb;35(2):1575-80.
Abstract
We aimed to explore the association between interleukin-17 (IL-17) polymorphisms, Helicobacter pylori infection, and subsites in gastric cancer risk in a Chinese population. We genotyped three promoter polymorphisms (rs2275913G>A, rs3748067C>T, and rs763780T>C) of IL-17 in a case-control study of 260 gastric cancer patients and 512 healthy controls. An unconditional multiple logistical regression model was used to calculate the effects of IL-17 gene polymorphisms on gastric cancer risk. The rs2275913 AA (adjusted OR = 1.69, 95 % CI = 1.15-2.49) and rs3748067 TT (adjusted OR = 1.73, 95 % CI = 1.03-2.94) genotypes were associated with an increased risk of gastric cancer. We observed a significant interaction among rs2275913G>A, rs3748067C>T, and H. pylori infection on the risk of gastric cancer (p for interaction of 0.036 and 0.048, respectively). H. pylori infection subjects carrying the rs2275913 AA (adjusted OR = 2.48, 95 % CI = 1.49-4.12) and rs3748067 TT (adjusted OR = 2.54, 95 % CI = 1.34-5.12) genotypes had a greatly increased risk of gastric cancer compared to negative H. pylori participants. Similarly, subjects carrying the rs2275913 AA (adjusted OR = 2.09, 95 % CI = 1.25-3.45) and rs3748067 TT (adjusted OR = 2.29, 95 % CI = 1.20-4.20) genotypes had a moderately increased risk of noncardia gastric cancer. A significant interaction was observed between the rs2275913G>A and rs3748067C>T genotype and subsites of gastric cancer (p for interaction of 0.044 and 0.008, respectively). The rs2275913G>A and rs763780T>C polymorphisms increase gastric cancer risk, and interact with H. pylori infection and subsites. These findings could be helpful in identifying individuals at increased risk for developing gastric cancer.
本研究目的在于在中国人群中探讨白介素17基因多态性，幽门螺杆菌感染和不同部位胃癌发病风险之间的关联。我们在260例胃癌患者和512例健康对照中对3个位于白介素17基因启动子区的多态性位点 (rs2275913G>A, rs3748067C>T, 和 rs763780T>C) 进行了基因分型。采用非条件多因素Logistic回归模型来评价基因多态性对胃癌发病风险的影响。结果显示，rs2275913AA基因型 (校正OR = 1.69, 95 % CI = 1.15-2.49) 和rs3748067 TT基因型 (校正OR = 1.73, 95 % CI = 1.03-2.94) 与胃癌的发病风险增加相关。并且，我们得出rs2275913G>A和rs3748067C>T多态性与幽门螺杆菌感染之间交互作用增加胃癌的发病风险(p值分别为 0.036和0.048)。携带rs2275913 AA基因型和rs3748067 TT基因型的幽门螺杆菌感染患者比幽门螺杆菌感染阴性患者具有更高的胃癌发生风险 (校正 OR值分别为2.48[1.49-4.12], 2.54[1.34-5.12]) 。同样，携带rs2275913 AA基因型和rs3748067 TT基因型的患者患非贲门胃癌的风险中度增高(校正OR值分别为2.09[1.25-3.45], 2.29[1.20-4.20])。rs2275913G>A和rs3748067C>T多态性与不同部位胃癌之间存在显著的交互作用(p值分别为0.044和0.008)。总之，rs2275913G>A和rs3748067C>T多态性增加了胃癌的发病风险，并且与幽门螺杆菌感染和胃癌发生部位之间存在交互作用。本研究结果有助于发现高胃癌发生风险的患者。
3、综述：细菌和上胃肠道疾病的发病——不仅仅是幽门螺杆菌
Review article: bacteria and pathogenesis of disease in the upper gastrointestinal tract--beyond the era of Helicobacter pylori.
Aliment Pharmacol Ther. 2014 Apr;39(8):767-79. doi: 10.1111/apt.12666. Epub 2014 Feb 24.
Abstract
BACKGROUND:
Study of the upper gastrointestinal microbiome has shown that other bacteria besides Helicobacter pylori flourish despite the hostile environment. Whilst H. pylori is the most studied bacteria in this region with a defined role in inflammation and neoplasia, it is apparent that other bacteria may contribute to UGI disease.
AIM:
To review current knowledge of bacteria inhabiting the oesophagus, stomach and duodenum.
METHODS:
Published studies on the upper gastrointestinal microbiome (extracted from PubMed during the last 20 years).
RESULTS:
The stomach is a hostile environment for bacteria; however, recent studies categorising the microbiota have shown surprising results. Helicobacter pylori has been intensively studied since 1984 and recent sequencing analysis of other gastric microbiota shows that H. pylori is not alone. Composition can be influenced by acid suppression, gastritis and abundance of H. pylori. Eradication of H. pylori, whilst decreasing gastric cancer is associated with an increase in asthma, reflux and obesity. A future approach may be to selectively eradicate bacteria which predispose to inflammation and cancer as opposed to a comprehensive knockout policy. In the oesophagus, viridans streptococci are the most common bacteria influenced by both oral and gastric bacteria. Oesophagitis and Barrett's oesophagus are characterised by a significant decrease in Gram-positive bacteria and an increase in Gram-negative bacteria. An inverse association of H. pylori and oesophageal adenocarcinoma is described. The duodenal microbiome has been shown to influence small intestinal bacterial overgrowth, irritable bowel syndrome and coeliac disease. The numbers of bacteria recoverable by culture are variable in the stomach mucosa and gastric juice, typically 10(2) -10(4) colony-forming units (CFU)/g or mL and in the oesophagus, up to 10(4) bacteria per mm(2) mucosal surface. In the small bowel, in health, 10(3) CFU/mL are normal.
CONCLUSION:
This review highlights current knowledge of upper gastrointestinal bacteria and associations with disease.
研究背景：有关上胃肠道微生物学研究发现胃肠环境中除幽门螺杆菌外存在其他类型的细菌繁殖。幽门螺杆菌是该领域研究最多的细菌，在炎症和肿瘤形成中有较明确的作用。很显然，其他细菌也可能与上胃肠道疾病的发病相关。
目的：本文目的在于对当前有关存在于食管、胃部和十二指肠细菌的相关研究作一综述。
研究方法：在PubMed中检索近20年来已经发表的上胃肠道微生物的相关研究。
研究结果：胃部环境不利于细菌生长，然而近年来有关微生物群的研究却显示不一致的结果。自1984年幽门螺杆菌便被大量研究，并且近期对其他微生物的测序分析发现并非仅仅幽门螺杆菌存在于胃部。这些微生物的组成受到胃酸负荷、胃炎和大量幽门螺杆菌的影响。根除幽门螺杆菌降低了胃癌的发生风险，但是却增加了哮喘、反流和肥胖的发生。未来的可能是选择性根除导致炎症或癌症的幽门螺杆菌而非全面根除策略。在食管最常见的细菌为草绿色链球菌，受到口腔和胃部细菌的影响。食管炎和Barrett食管以革兰氏阳性细菌明显减少，而革兰氏阴性细菌明显增多为特点。有研究显示幽门螺杆菌和食管腺癌之间负相关。十二指肠部细菌则对小肠细菌过度生长、肠易激综合征和乳糜泻产生影响。通过细菌培养获得的细菌数目有很大的差异，通常在胃粘膜和胃液中102-104的菌落-单位CFU每克或者每毫升；在食道中，每平方毫米黏膜表面高达104细菌；在健康者小肠中，正常为103CFU每毫升。。
结论：本综述突出强调了当前有关上胃肠道细菌及其与疾病之间关联的研究。
4、合并胃肠上皮化生胃组织活检诊断幽门螺杆菌的准确性研究
Accuracy of biopsies for Helicobacter pylori in the presence of intestinal metaplasia of the stomach.
Galiatsatos P1, Wyse J, Szilagyi A.
Turk J Gastroenterol. 2014 Feb;25(1):19-23. doi: 10.5152/tjg.2014.6476.
Abstract
BACKGROUND/AIMS:
Gastric cancer is the second leading cause of cancer-related death worldwide. The majority of gastric cancers is "intestinal-type" adenocarcinoma, caused in part by H. pylori infection. Chronic gastritis leading to atrophy and intestinal metaplasia (IM) can result in cancer. Studies have demonstrated reversibility of mucosal atrophy following H. pylori eradication. Concern has been raised regarding the sensitivity of gastric biopsy for H. pylori detection in the context of IM.
MATERIALS AND METHODS:
All cases of IM on gastric biopsy from a single gastroenterologist's outpatient practice were retrospectively reviewed from February 1, 2006 until May 31, 2012.
RESULTS:
In total, 105 IM cases were found, of which 37 (35.2%, 95% CI: 26.3-45.2) were H. pylori-positive on biopsy. Charts of the remaining 68 patients were reviewed for availability of other tests, namely urea breath test (UBT) and serology. Of 43 H. pylori-negative patients who underwent a UBT, 10 were positive for the infection (23.3%, 95% CI: 12.3-39.0). Amongst patients with coexisting autoimmune gastritis (AIG), 4 out of 9 (44.4%, 95% CI: 15.3-77.3) also had evidence of H. pylori infection by UBT, despite negative histology.
CONCLUSION:
For cases of gastric IM with negative histology for H. pylori, UBT should be considered, even in cases of AIG, as this may alter the management and clinical course for patients.
研究背景和目的：胃癌是世界范围内第二大癌症相关死亡原因。大多数胃癌为与幽门螺杆菌感染相关的肠型腺癌。慢性胃炎导致的胃黏膜萎缩和肠上皮化生可以导致胃癌。有研究显示根除幽门螺杆菌可以逆转胃黏膜萎缩。因此，对于合并肠上皮化生者胃黏膜活检诊断幽门螺杆菌感染的敏感性成为人们关注的问题。
材料和方法：回顾评价了单一胃肠病专家门诊自2006年2月1日至2012年5月31日期间的所有合并胃肠上皮化生并行胃活检的患者。
结果：共纳入105例胃肠上皮化生患者，其中37例(35.2%, 95% CI: 26.3-45.2)通过胃黏膜活检诊断合并幽门螺杆菌感染。其余的68例患者进行了其他可行的检测手段，如尿素呼气试验和血清学检验。43例幽门螺杆菌阴性患者采用尿素呼气试验，发现10例阳性患者(23.3%, 95% CI: 12.3-39.0)。其中，合并自身免疫性胃炎患者中，4/9例(44.4%, 95% CI: 15.3-77.3)患者经尿素呼气试验检查发现幽门螺杆菌阳性。
结论：对于合并胃肠上皮化生，甚至是自身免疫性胃炎，而胃黏膜活检显示幽门螺杆菌阴性的患者需要考虑行尿素呼气试验，这对于疾病的诊治和临床疗程有重要的指导意义。
5、幽门螺杆菌感染与儿童急性细菌性腹泻的关系
The Relation between Helicobacter pylori Infection and Acute Bacterial Diarrhea in Children.
Monajemzadeh M1, Abbasi A2, Tanzifi P3, Taba Taba Vakili S4, Irani H5, Kashi L5.
Int J Pediatr. 2014;2014:191643. doi: 10.1155/2014/191643. Epub 2014 Feb 19.
Abstract
Background. H. pylori infection leads to chronic gastritis in both children and adults. But recently, there are arising theories of its protective effect in diarrheal diseases. Aim. To explore the prevalence of H. pylori infection in children with bacterial diarrhea and compare it with healthy controls. Patients and Methods. Two matched groups consisted of 122 consecutive children, aged 24-72 months old, with acute bacterial diarrhea, who had Shigellosis (N = 68) and Salmonellosis (N = 54) as patients group and 204 healthy asymptomatic children as control group enrolled in this study. Results. The prevalence of H. pylori infection in healthy control children was significantly higher than in patients group, (odds ratio = 3.6, 95% CI: 1.33-9.5, P = 0.007). In our study, only 2/54 Salmonella infected patients and 3/68 of Shigellosis had evidence of H. pylori infection, while normal control children had 27/204 infected individuals. Conclusion. H. pylori infection may play a protective role against bacterial diarrhea in children. So it is important to consider all of the positive and negative aspects of H. pylori infection before its eradication.
研究背景：幽门螺杆菌感染可以导致儿童及成人慢性胃炎。然而，近期越来越多研究表明幽门螺杆菌在腹泻疾病中的保护作用。
研究目的：探讨幽门螺杆菌在细菌性腹泻儿童和正常对照者中的流行情况。
研究方法：病例组包括122例年龄在24-72个月合并细菌腹泻的儿童，分为细菌性痢疾（n=68）和沙门氏菌病（n=54）。对照组为204例无症状健康儿童。
研究结果：健康对照儿童中幽门螺杆菌感染率明显高于病例组儿童（OR = 3.6, 95% CI: 1.33-9.5, P = 0.007）。本研究中，细菌性痢疾组仅有 3/68例，沙门氏菌病组仅有2/54例提示合并幽门螺杆菌感染，而在健康对照儿童中有27/204例。
结论：幽门螺杆菌可能在儿童细菌性腹泻中起保护作用。因此在儿童中根除幽门螺杆菌需全面考虑利弊因素。