小儿幽门螺杆菌病研究进展

小儿幽门螺杆菌（Helicobacter Pylori．HP）病．是指HP感染后引起的疾病，包括胃炎、消化性溃疡、胃癌等以及胃肠道外与之有关的疾病．该病原体是2005年诺贝尔奖得主者Barry Marshall（巴里．马歇尔）于1986年首次报道的．此后世界各地投入巨资用于研究，现已有15000多篇论著发表．其中1998年以来发表的论著之超过6500篇．治疗方案非常多，但疗效并不满意．因此对“HP疫苗”和新特效抗生素的研制是非常必要的。

含左氧氟沙星三联方案治疗幽门螺杆菌病阳性消化性溃疡效果评价

目的:探讨含左氧氟沙星三联方案治疗幽门螺杆菌阳性消化性溃疡临床价值。方法:110例幽门螺杆菌阳性消化性溃疡患者按就诊时间顺序将本组患者随机均分为两组各55例。对照组标准剂量质子泵抑制剂+克拉霉素+甲硝唑治疗;观察组标准剂量质子泵抑制剂+阿莫西林+左氧氟沙星治疗。结果:治疗1个疗程后观察组总有效94.45%与对照组的92.73%比较,差异无统计学意义(P>0.05);两组患者药物不良反应发生率29.09%、30.91%,差异无统计学意义(P>0.05);复查幽门螺杆菌病观察组阴性94.45%,高于对照组的72.73%,差异有统计学意义(P<0.05);随访(1.47±0.52)年,观察组溃疡复发7.27%,低于对照组的18.18%,差异有统计学意义(P<0.05)。结论:含左氧氟沙星三联疗法治疗幽门螺杆菌病阳性消化性溃疡,能有效治疗溃疡,提高幽门螺杆菌清除率,减少溃疡复发。

幽门螺杆菌相关性胃肠粘膜病患儿血清CagA抗体、VacA抗体检测及其临床意义

为了解幽门螺杆菌(Helicobacter pylori,H.pylori)相关性胃肠粘膜病患儿血清中细胞毒素相关基因抗原(CagA)、空泡毒素抗原(VacA)的有无及其临床意义,应用免疫印迹法对46例慢性胃炎和25例消化性溃疡患儿血清CagA抗体、VacA抗体进行了检测。结果:①慢性胃炎小儿血清H.Pylori CagA抗体(+)、VacA抗体(+)检出率为28.3％,消化性溃疡患儿为64.0％,两组比较差异有显著性(P<0.05);②对慢性胃炎炎症活动程度进行分组检测,中、重度急性活动性胃炎患儿中H.Pylori CagA抗体(+)、VacA抗体(+)检出率为50.0％,与轻症者比较差异有显著性(P<0.05)。提示 H.pylori菌株存在不同致病能力,CagA、VacA是致小儿 H.Pylori相关性胃肠粘膜病重要的毒力因素;通过检测CagA、VacA抗体,可及时指导临床治疗。

标准四联疗法及序贯疗法治疗胃溃疡幽门螺杆菌阳性患者的基本疗效观察

目的:探究将标准四联疗法以及血管疗法应用于胃溃疡幽门螺杆菌阳性患者治疗中的效果,分析其临床可用价值。方法:将2016年9月至2019年8月作为本次研究实验时段,录入该时段我院数据库内资料,登记有效的胃溃疡幽门螺杆菌阳性患者96例作为本次研究实验对象录入Excel表格,按照随机均分法进行两组随机均分,且按照实验习惯分别记名为对照组与实验组。对照组患者选择标准四联疗法对疾病进行治疗,实验组患者则将序贯疗法应用于患者的治疗中,治疗完成后评价两组患者的消化道症状评分以及溃疡愈合状况,同时记录两组患者治疗后的并发症发生率,对比结果。结果:两组患者在治疗完成后,其胃溃疡愈合状况较为良好,而实验组患者在治疗后的总愈合率达到93.715%,相较于对照组的77.08%来说明显更高,数据对比差异显著(χ^(2)=8.1417,P=0.0000)。两组患者在治疗完成后,患者的临床消化到症状均有所改善,两组患者的消化道评分有所降低,而实验组患者的消化道症状评分相较于对照组来说明显更低,提示实验组患者在治疗后个体状况恢复更优,组间差异对比(P<0.05)。两组患者在治疗完成后,均有不同程度的不良反应发生状况,但相较于对照组来说,实验组患者的不良反应发生率更低,总发生率约为4.17%,低于对照组的27.08%,数据对比差异显著(χ^(2)=9.2641,P=0.0000)。结论:在对胃溃疡幽门螺杆菌阳性患者进行治疗时,序贯疗法有利于根除患者体内的幽门螺杆菌,对于患者的溃疡愈合来说有良好的促进作用,并且这种治疗方案的疗效明显优于标准四联疗法,同时这种治疗方案还能有助于降低患者的不良反应,可作为胃溃疡幽门螺杆菌阳性患者的基础治疗方案。

上消化道疾病患者幽门螺杆菌感染情况调查

幽门螺杆菌病是指感染幽门螺杆菌（Hp）后引起的疾病，包括胃炎、消化性溃疡、胃癌等，及胃肠道外与之相关的疾病。澳大利亚学者Warren和Marshall 1983年报道，在人胃黏膜活检组织中发现，并在厌氧环境下培养出幽门螺杆菌，认为幽门螺杆菌与慢性胃炎和消化性溃疡关系密切，同时又是引起胃癌和胃黏膜相关淋巴癌的危险因素。

警惕新传染病

继“非典型肺炎”在全球暴发流行之后，“禽流感”又肆虐一时。这些传染病相对于以往人们所认知的旧传染病如结核病、天花、麻疹等，称之为“新传染病”。上个世纪70年代以来，人们新认识或新发现的能造成地域性或国际性公共卫生问题的传染病，已经被确认将近40种，除非典型肺炎、禽流感外，较出名的还有艾滋病、军团菌病、疯牛病、丙型肝炎、庚型肝炎、戊型肝炎、流行性出血热、幽门螺杆菌病、埃博拉出血热、莱姆病等。

幽门螺杆菌与胃食管反流病的关系探讨

胃食管反流痛（GERD）是消化道常见的胃肠动力障碍性痰病，在我国总体发病率为5．77％，其病因、发病机制尚未完全明确，其发生发展是一个多因素的过程，包括多种病因引起的食管抗反流和清除机制障碍。幽门螺杆菌（Hp）感染作为慢性胃炎、消化性溃癌的主要致病因素、胃癌启动因子的观点已得鲥公认，但GERD与Hp的关系尚存在较大的争议。一种观点认为Hp在GERD的发生中起保护作用，根除Hp可能使部分人群的反流症状加重。另一种观点认为Hp感染可增加胃酸分泌，应该采取根除Hp治疗。本文对60例GERD患者行胃镜检查和幽门螺杆菌（Hp）检测，以探讨其相关性。

This year's Nobel Prize to gastroenterology:Robin Warren and Barry Marshall awarded for their discovery of Helicobacter pylori as pathogen in the gastrointestinal tract

TO THE EDITORPeptic ulcer disease is a major health care concern in the society today, in view of personal suffering as well as economical health care costs.

CagA+ H pylori infection is associated with polarization of T helper cell immune responses in gastric carcinogenesis

AIM:To characterize the immune responses including local and systemic immunity induced by infection with H pylori,especially with CagA+ H pylori strains and the underlying immunopathogenesis. METHODS:A total of 711 patients with different gastric lesions were recruited to determine the presence of H pylori infection and cytotoxin associated protein A (CagA),the presence of T helper (Th) cells and regulatory T (Treg) cells in peripheral blood mononuclear cells (PBMCs),expression of plasma cytokines,and RNA and protein expression of IFN-γ and IL-4 in gastric biopsies and PBMCs were determined by rapid urease test,urea 14C breath test,immunoblotting test,flow cytometry ,real time RT-PCR and immunohistochemistry. RESULTS:Of the patients,629 (88.47%) were infected with H pylori ; 506 (71.16%) with CagA+ and 123 (17.30%) with CagA- strains. Among patients infected with CagA+ H pylori strains,Th1-mediated cellular immunity was associated with earlier stages of gastric carcinogenesis,while Th2-mediated humoral immunity dominated the advanced stages and was negatively associated with an abundance of Treg cells. However,there was no such tendency in Th1/Th2 polarization in patients infected with CagA- H pylori strains and those without H pylori infection. CONCLUSION:Polarization of Th cell immune responses occurs in patients with CagA+ H pyloriinfection,which is associated with the stage and severity of gastric pathology during the progression of gastric carcinogenesis. This finding provides further evidence for a causal role of CagA+ H pylori infection in the immunopathogenesis of gastric cancer.

Causal role of Helicobacter pylori infection in gastric cancer

Gastric cancer is the second most frequent cancer in the world, accounting for a large proportion of all cancer cases in Asia, Latin America, and some countries in Europe. Helicobacter pylori（H pylori） is regarded as playing a specific role in the development of atrophic gastritis, which represents the most recognized pathway in multistep intestinal-type gastric carcinogenesis. Recent studies suggest that a combination of host genetic factors, bacterial virulence factors, and environmental and lifestyle factors determine the severity of gastric damage and the eventual clinical outcome of H pylori infection. The seminal discovery of Hpylori as the leading cause of gastric cancer should lead to effective eradication strategies. Prevention of gastric cancer requires better screening strategies to identify candidates for eradication.

Helicobacter pylori infection and respiratory diseases:a review

In the past few years,a variety of extradigestive disorders, including cardiovascular,skin,rheumatic and liver diseases, have been associated with Helicobacter pylori(H.pylori) infection.The activation of inflammatory mediators by H.pylori seems to be the pathogenetic mechanism underlying the observed associations.The present review summarizes the current literature,including our own studies,concerning the association between H.pyloriinfection and respiratory diseases. A small number of epidemiological and serologic,case- control studies suggest that H.pylori infection may be associated with the development of chronic bronchitis.A frequent coexistence of pulmonary tuberculosis and H.pylori infection has also been found.Moreover,recent studies have shown an increased H.pyloriseroprevalence in patients with bronchiectasis and in those with lung cancer.On the other hand,bronchial asthma seems not to be related with H.pylori infection. All associations between H.pylori infection and respiratory diseases are primarily based on case-control studies, concerning relatively small numbers of patients.Moreover, there is a lack of studies focused on the pathogenetic link between respiratory diseases and H.pylori infection. Therefore,we believe that larger studies should be undertaken to confirm the observed results and to clarify the underlying pathogenetic mechanisms.

Interleukin-1 and TNF-α polymorphisms and Helicobacter pylori in a Brazilian Amazon population

AIM： To study the association between Interleukin-1 （IL-1） and tumor necrosis factor （TNF）-α polymorphisms, infection by Helicobacter pylori （H pylori） and the development of gastrointestinal diseases.METHODS： Genomic DNA was extracted from the peripheral blood of 177 patients with various gastrointestinal diseases and from 100 healthy volunteers. The polymorphisms in IL-1β and TNF-α genes were analyzed using the polymerase chain reactionrestriction fragment length polymorphism method （PCRRFLP） and those from IL-1RN with PCR. The presence of infection due to H pylori and the presence of the CagA toxin were detected by serology. The histopathological parameters in the gastric biopsies of the patients were according to the Sydney classification.RESULTS： A comparison of the frequencies of the different polymorphisms studied among the patients and the control group demonstrated that the allele IL- 1RN＊2 was more frequent among patients with gastric ulcers and adenocarcinoma. Carriers of the allele IL- RN＊2 and those with reactive serology for anti-CagA IgG had a greater risk of developing peptic ulcer and gastric adenocarcinoma, as well as a higher degree of inflammation and neutrophilic activity in the gastricCONCLUSION： Our results indicate a positive association between IL-1RN gene polymorphism and infection by positive H pylori CagA strains and the development of gastric ulcers and adenocarcinoma.

Association between cag-pathogenicity island in Helicobacter pylori isolates from peptic ulcer,gastric carcinoma,and non-ulcer dyspepsia subjects with histological changes

AIM： To investigate the presence of the cag-pathogenicity island and the associated histological damage caused by strains with complete cag-PAI and with partial deletions in correlation to the disease status. METHODS： We analyzed the complete cag-PAI of 174 representative Helicobacter pylori （H pylori ） clinical isolates obtained from patients with duodenal ulcer, gastric ulcer, gastric cancer, and non-ulcer dyspepsia using eight different oligonucleotide primers viz cagA1, cagA2, cagAP1, cagAP2, cagE, cagT, LEC-1, LEC-2 spanning five different loci of the whole cag-PAI by polymerase chain reaction （PCR）. RESULTS： The complete screening of the genes comprising the cag-PAI showed that larger proportions of subjects with gastric ulcer （97.8%） inhabited strains with complete cag-PAI, followed by gastric cancer （85.7%）, non-ulcer dyspepsia （7.1%）, and duodenal ulcer （6.9%）, significant differences were found in the percentage distribution of the genes in all the clinical groups studied. It was found that strains with complete cag-PAI were able to cause severe histological damage than with the partially deleted ones. CONCLUSION： The cag-PAI is a strong virulent marker in the disease pathogenesis as it is shown that a large number of those infected with strain with complete cag-PAI had one or the other of the irreversible gastric pathologies and interestingly 18.5% of them developed gastric carcinoma. The presence of an intact cag- PAI correlates with the development of more severe pathology, and such strains were found more frequently in patients with severe gastroduodenal disease. Partial deletions of the cag-PAI appear to be sufficient to render the organism less pathogenic.

Modalities of testing Helicobacter pylori in patients with nonmalignant bile duct diseases

AIM:This paper describes the procedure of detection of Helicobacter pylori(H.pylori)in bile specimens in patients suffering from benign diseases of biliary ducts(lithiasis with/without nonspecific cholangitis). METHODS:The group of 72 patients entering the study consisted of 32 male and 40 female(45 % and 55 %, respectively).Bile was obtained during ERCP in 68 patients, and during cholecystectomy in 4 patients.A fast urease test (FUT)to determine the existence of H.pylori in gastric mucosa was carried out for all the patients during the endoscopic examination.The existence of genetic material of H.pylori was determined by detection of ure A gene by the method of nested PCR.The results of this reaction were shown by electrophoresis on 10 g·L^(-1)agarose gel in a band of 256 bp. RESULTS:The majority of the patients included in our study had biliary lithiasis without signs of cholangitis(48 patients, 67 %),whereas other patients were complicated by cholangitis(17 patients,24 %).Seven patients(9 %)had normal ERCP,forming thus the control group.In the group of patients with lithiasis 26 patients(24.2 %)had positive PCR of H.pylori in bile and among the patients with associated cholangitis positive PCR was detected in 9 patients(52.9 %).Among the seven patients with normal ERCP only one(14 %)had positive PCR of H.pylori.A high percentage of H.pylori infection of gastric mucosa was observed(57 patients,79 %).It was also observed that its slightly higher positivity was in the patients with distinct bile pathology:81% FLIT positive patients in the group with choledocholithiasis alone and 76 % in the group with choledocholithiasis associated with cholangitis.Seventy-one percent of the patients with regular findings had positive FUT.CONCLUSION: The prevalence of H. pylori infection both in bile and in gastric mucosa in patients with benign diseases of biliary ducts does not show a statistically significant difference in relation to the prevalence of the same with the patients with normal ERCP. The existence of H. pylori infection possibly does not play a role in pathogenesis of benign biliary diseases.

Factors predicting survival in patients with proximal gastric carcinoma involving the esophagus

AIM： To investigate the clinicopathologic features which predict surgical overall survival in patients with proxima gastric carcinoma involving the esophagus （PGCE）. METHODS： Electronic pathology database established in the Department of Pathology of the Nanjing Drum Tower Hospital was searched for consecutive resection cases of proximal gastric carcinoma over the period from May 2004 through July 2009. Each retrieved pa- thology report was reviewed and the cases with tumors crossing the gastroesophageal junction line were se- lected as PGCE. Each tumor was re-staged, following the guidelines on esophageal adenocarcinoma, accord- ing to the 7th edition of the American Joint Commission on Cancer Staging Manual. All histology slides were studied along with the pathology report for a retrospec- tive analysis of 13 clinicopathologic features, i.e., age, gender, Helicobacter pylori （H. pylon} infection, surgical modality, Siewert type, tumor Bormann＇s type, size, dif- ferentiation, histology type, surgical margin, lympho- vascular and perineural invasion, and pathologic stage in relation to survival after surgical resection. Prognos- tic factors for overall survival were assessed with uni- and multi-variate analyses. RESULTS： Patients＇ mean age was 65 years （range： 47-90 years）. The male： female ratio was 3.3. The 1-, 3- and 5-year overall survival rates were 87%, 61% and 32%, respectively. By univariate analysis, age, male gender, H. pylori, tumor Bormann＇s type, size, histology type, surgical modality, positive surgical margin, lym- phovascular invasion, and pT stage were not predictive for overall survival; in contrast, perineural invasion （P = 0.003）, poor differentiation （P = 0.0003）, 〉 15 to- tal lymph nodes retrieved （P = 0.008）, positive lymph nodes （P = 0.001）, and distant metastasis （P = 0.005） predicted poor post-operative overall survival. Celiac axis nodal metastasis was associated with significantly worse overall survival （P = 0.007）. By multivariate analysis, ≥ 16 positive nodes （P = 0.018）, lymph node ratio 〉 0.2 （P = 0.003）, and overall pathologic stage （P= 0.002） were independent predictors for poor overa survival after resection. CONCLUSION： Patients with PGCE showed worse over- all survival in elderly, high nodal burden and advanced pathologic stage. This cancer may be more accurately staged as gastric, than esophageal, cancer.

Interleukin-17 levels in Helicobacter pylori-infected gastric mucosa and pathologic sequelae of colonization

AIM： To determine the role of interleukin （IL）-17 in gastric ulcerogenesis. METHODS： Thirty-six gastric ulcer （GU） patients and 29 non-ulcer （NU） patients were enrolled in this study. Mucosal biopsy samples were obtained from the gastric antrum and GU site during endoscopy. Samples were used in in situ stimulation for 48 h in the presence of 10 ug/mL phytohemagglutinin-P （PHA）, histological examination, and Helicobacter pylori（Hpylon） culture. IL-17 and IL-8 protein levels in culture supematants were assayed by ELISA. IL- 17 mRNA expression was analyzed by reverse transcriptasepolymerase chain reaction （RT-PCR）. Hpylori cagA and vacA status was assessed by reverse hybridization using a line probe assay （UPA）. IL-8 levels in culture supematants were assayed after AGS cells were co-cultured with Hpylori strain 26 695 or recombinant human （rh） IL-17. RESULTS： All 36 GU patients and 15 of 29 NU patients were found to be Hpy/or/-positive, while 14 NU patients were Hpylori-nogative. All 51 H pylori strains from both GU and NU patients were cagA- and vacAsl/ml-positive. Antral mucosal tissues from H pylori-positive patients contained significantly （H pylori-positive NU patients： median 467 pg/mg/protein, range 53-2 499; Hpylori negative NU patients： median 104 pg/mg/protein, range 16-312, P〈0.0005） higher levels of IL-17 than those from uninfected patients. IL-17 levels at the ulcer site were significantly （ulcer site： median 1 356 pcj/mg/protein, range 121-1 3730; antrum： median 761 pg/mg/protein, range 24-7 620, P〈0.005） higher than those at distant sites in the antrum. Biopsies from H pylori-positive GU and NU patients showed IL-17 mRNA expression in all samples whereas those from the antrum of the Hpylori-negativecontrols showed no detectable expression. A significant correlation was seen between IL-17 and IL-8 levels at each biopsy site （ulcer： r = 0.62,P〈0.0001; antrum： r = 0.61, P〈0.0001） in GU patients. RhIL-17 and Hpylori strain 26 695 each stimulated IL-8 production from AGS cells. CONCLUSION： IL-17 may play an important role in the inflammatory response to Hpyloricolonization, and may ultimately influence the outcome of H pylori-associated diseases that arise within the context of gastritis.

Latest insights into the effects of Helicobacter pylori infection on gastric carcinogenesis

There appears to be the strong association between Helicobacter pylori （H pylori） and gastric cancer. We reviewed the latest evidences about the effects of H pylori infection on gastric carcinogenesis, classified into epidemiology, dynamics of gastric mucosal changes, DNA damages, virulence factors, host factors, and source of gastric malignancy. Through the considerable progress made in research into virulence factors resulting from differences between Hpylori strains, such as cagA positivity, as well as into host factors, such as gene polymorphisms, a diverse spectrum of H pyloriassociated diseases, including gastric cancer, is beginning to lend itself to elucidation. The impact of the novel hypothesis advanced by Houghton et al proposing bonemarrow derived stem cells （BMDC） as a potential source of gastric malignancy on evolving research remains to be seen with interest. Further progress in research into H pylori eradication as a viable prophylaxis of gastric cancer, as well as into the mechanisms of gastric carcinogenesis, is to be eagerly awaited for the current year and beyond.

Effects of Helicobacter pylori eradication on atrophic gastritis and intestinal metaplasia: A 3-year follow-up study

AIM: To investigate the effect of H pylori eradication on atrophic gastritis and intestinal metaplasia (IM).METHODS: Two hundred and fifty-nine patients with atrophic gastritis in the antrum were included in the study, 154 patients were selected for H pylori eradication therapy and the remaining 105 patients served as untreated group. Gastroscopy and biopsies were performed both at the beginning and at the end of a 3-year follow-up study. Gastritis was graded according to the updated Sydney system.RESULTS: One hundred and seventy-nine patients completed the follow-up, 92 of them received H pylori eradication therapy and the remaining 87 H pyloriinfected patients were in the untreated group. Chronic gastritis, active gastritis and the grade of atrophy significantly decreased in H pylori eradication group (P＜0.01). However, the grade of IM increased in H pylori -infected group (P＜0.05).CONCLUSION: H pylori eradication may improve gastric mucosal inflammation, atrophy and prevent the progression of IM.

Delayed gastric emptying is associated with pylorus-preserving but not classical Whipple pancreaticoduodenectomy:A review of the literature and critical reappraisal of the implicated pathomechanism

Pylorus-preserving pancreaticoduodenectomy （PPPD） is nowadays considered the treatment of choice for periampullary tumors, namely carcinoma of the head, neck, or uncinate process of the pancreas, the ampulla of Vater, distal common bile duct or carcinoma of the peri-Vaterian duodenum. Delayed gastric emptying （DGE） comprises one of the most troublesome complications of this procedure. A search of the literature using Pubmed/IVledline was performed to identify clinical trials examining the incidence rate of DGE following standard Whipple pancreaticoduodenectomy （PD） vs PPPD. Additionally we performed a thorough in-depth analysis of the implicated pathomechanism underlying the occurrence of DGE after PPPD. In contrast to early studies, the majority of recently performed clinical trials demonstrated no significant association between the occurrence of DGE with either PD or PPPD. PD and PPPD procedures are equally effective operations regarding the postoperative occurrence of DGE. Further randomized trials are required to investigate the efficacy of a recently reported （but not yet tested in largescale studies） modification, that is, PPPD with antecolic duodenojejunostomy.