Regression of gastric T cell lymphoma with eradication of Helicobacter pylori

Helicobacter pylori is thought to be important in the pathogenesis of chronic active gastritis, peptic ulceration, gastric adenocarcinoma, and gastric B cell lymphoma of mucosa associated lymphoid tissue. The mechanism of evolution from chronic gastritis to monoclonal B cell proliferation is not known but is thought to be dependent on antigen specific T cells to H pylori and its products. Here, we report a case of gastric T cell lymphoma associated with chronic H pylori gastritis which regressed with eradication of the organism. This is the first report of a gastric T cell lymphoma regressing with H pylori eradication, and suggests a causal link between primary gastric T cell lymphoma and this organism.     

Concomitant therapy achieved the best eradication rate for Helicobacter pylori among various treatment strategies

AIM: To compare the Helicobacter pylori(H.pylori) eradication rate of clarithromycin-based triple therapy,metronidazole-based triple therapy,sequential therapy and concomitant therapy.METHODS: A total of 680 patients infected with H.pylori were divided into 4 groups and each group was treated with a different eradication therapy.Clarithromycin-based triple therapy was applied to the first group [rabeprazole,amoxicillin and clarithromycin(PAC) group: proton pump inhibitor(PPI),amoxicillin,clarithromycin],whereas the second group was treated with metronidazole-based triple therapy [rabeprazole,amoxicillin and metronidazole(PAM) group: PPI,amoxicillin,metronidazole].The third group was treated with rabeprazole and amoxicillin,followed by rabeprazole,clarithromycin and metronidazole(sequential group).The final group was simultaneously treated with rabeprazole,amoxicillin clarithromycin and metronidazole(concomitant therapy group).In the case of a failure to eradicate H.pylori,second-line quadruple and third-line eradication therapies were administered.RESULTS: The per protocol(PP) analysis was performed on 143,139,141 and 143 patients in the PAC,PAM,sequential and concomitant groups,respectively.We excluded patients who did not receive a C13-urea breath test(22,20,23 and 22 patients,respectively) and patients with less than an 80% compliance level(5,11,6 and 5 patients,respectively).The eradication rates were 76.2%(109/143) in the PAC group,84.2%(117/139) in the PAM group,84.4%(119/141) in the sequential group and 94.4%(135/143) in the concomitant group(P = 0.0002).All 14 patients who failed second-line therapy were treated with thirdline eradication therapy.Among these 14 patients,6 infections were successfully eradicated with the thirdline therapy.Both PP and intention-to-treat analysis showed an eradication rate of 42.9%(6/14).In the PAC group,3 of 4 patients were successfully cured(3/4,75%); 2 of 2 patients in the PAM group(2/2,100%) and 1 of 5 patients in the sequential group(1/5,20%) were also cured.In the concomitant group,all 3 patients failed(0/3,0%).CONCLUSION: The eradication rate for the concomitant therapy was much higher than those of the standard triple therapy or sequential therapy(Clinical Trials.gov number NCT01922765).     

四联疗法与序贯疗法在幽门螺杆菌根除补救治疗中的疗效比较

[目的]比较四联疗法与序贯疗法在幽门螺杆菌(Hp)根除补救治疗中的疗效及安全性,旨在寻找一种有效、安全、经济的补救治疗方案。[方法]将首次根除Hp治疗失败的90例慢性胃炎患者,随机分为四联疗法组和序贯疗法组,每组45例。四联疗法组患者治疗方案为埃索美拉唑、枸橼酸铋钾、阿莫西林、莫西沙星,疗程14d。序贯疗法组患者治疗方案为前5d给予埃索美拉唑、阿莫西林;后5d给予埃索美拉唑、克拉霉素、奥硝唑。所有患者在疗程结束停药4周后行14 C尿素呼气试验检测Hp。比较2组患者治疗前后的不良反应。[结果]四联疗法组Hp根除率(91.1%)显著高于序贯疗法组(75.6%),差异有统计学意义(P<0.05)。2组不良反应均很轻微,组间不良反应发生率比较差异无统计学意义(P>0.05)。[结论]对于Hp补救治疗,四联疗法较序贯疗法疗效更好,且不良反应小,患者依从性好,值得在临床上推广。     

幽门螺旋杆菌引起胃黏膜免疫损伤机制研究进展

幽门螺旋杆菌(Helicobacter plyori,Hp)是消化道疾病最常见的病因,通过多种机制诱导炎症通路激活、免疫细胞及炎症因子释放改变胃黏膜周围微环境引起慢性炎症,持久性的慢性炎症可导致胃黏膜萎缩、甚至诱发胃癌.正常机体T淋巴细胞在免疫反应中起主导作用,其中正向调节与负向调节系统相互诱导和制约T细胞网络维持免疫系统平衡,当Hp感染后两项调节比例出现异常,导致免疫系统紊乱从而引起免疫损伤.近年来免疫细胞的分子生物学研究已经成为临床过继性细胞免疫治疗的理论基础.     

The B‐cell‐activating factor signalling pathway is associated with Helicobacter pylori independence in gastric mucosa‐associated lymphoid tissue lymphoma without t(11;18)(q21;q21)

We previously reported that activation of the B‐cell‐activating factor (BAFF) pathway upregulates nuclear factor‐κB (NF‐κB) and induces BCL3 and BCL10 nuclear translocation in Helicobacter pylori (HP)‐independent gastric diffuse large B‐cell lymphoma (DLBCL) tumours with evidence of mucosa‐associated lymphoid tissue (MALT). However, the significance of BAFF expression in HP independence of gastric low‐grade MALT lymphomas without t(11;18)(q21;q21) remains unexplored. Sixty‐four patients who underwent successful HP eradication for localized HP‐positive gastric MALT lymphomas without t(11;18)(q21;q21) were studied. BAFF expression was significantly higher in the HP‐independent group than in the HP‐dependent group [22/26 (84.6%) versus 8/38 (21.1%); p < 0.001]. Similarly, BAFF receptor (BAFF‐R) expression (p = 0.004) and nuclear BCL3 (p = 0.004), BCL10 (p < 0.001), NF‐κB (p65) (p = 0.001) and NF‐κB (p52) (p = 0.005) expression were closely correlated with the HP independence of these tumours. Moreover, BAFF overexpression was significantly associated with BAFF‐R expression and nuclear BCL3, BCL10, NF‐κB (p65) and NF‐κB (p52) expression. These findings were further validated in an independent cohort, including 40 HP‐dependent cases and 18 HP‐independent cases of gastric MALT lymphoma without t(11;18)(q21;q21). The biological significance of BAFF signalling in t(11;18)(q21;q21)‐negative lymphoma cells was further studied in two types of lymphoma B cell: OCI‐Ly3 [non‐germinal centre B‐cell origin DLBCL without t(11;18)(q21;q21) cell line] and MA‐1 [t(14;18)(q32;q21)/IGH‐MALT1‐positive DLBCL cell line]. In both cell lines, we found that BAFF activated the canonical NF‐κB and AKT pathways, and induced the formation of BCL10–BCL3 complexes, which translocated to the nucleus. BCL10 and BCL3 nuclear translocation and NF‐κB (p65) transactivation were inhibited by either LY294002 or by silencing BCL3 or BCL10 with small interfering RNA. BAFF also activated non‐canonical NF‐κB pathways (p52) through tumour necrosis factor receptor‐associated factor 3 degradation, NF‐κB‐inducing kinase accumulation, inhibitor of κB kinase (IKK) α/β phosphorylation and NF‐κB p100 processing in both cell lines. Our data indicate that the autocrine BAFF signal transduction pathway contributes to HP independence in gastric MALT lymphomas without the t(11;18)(q21;q21) translocation. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

上消化道症状与幽门螺杆菌感染及胃癌前疾病的相关性研究

目的探讨上消化道症状与幽门螺杆菌(Hp)感染及胃黏膜癌前病变的相关性。方法临床纳入2010年1月至2014年10月期间门诊初诊为慢性胃炎的患者,其中上消化道症状阳性组的患者360例,上消化道症状阴性组的患者360例,所有患者均通过碳14呼气试验进行Hp检测及胃镜下活检检测诊断,分别比较有无上消化道症状对患者的Hp阳性检出率之间的关系;以及有无上消化道症状与胃镜活检诊断为胃癌前疾病的相关度。结果上消化道症状阳性组Hp检出率高于上消化道症状阴性组(P0.05);上消化道症状阳性组的慢性胃炎伴不典型增生组的发病率明显高于上消化道症状阴性组,差异有统计学意义(P0.05)。结论上消化道症状与Hp感染具有相关性,上消化道症状与慢性胃炎伴不典型增生具有相关性。     

Effectiveness of Omeprazole- Versus Lansoprazole-Based Triple Therapy for <Emphasis Type="Italic">Helicobacter pylori</Emphasis> Eradication

Triple therapy with a proton pump inhibitor (PPI), amoxicillin, and clarithromycin is widely accepted for Helicobacter pylori eradication. The choice of PPI for triple therapy in Israel is arbitrary, with no preference for any one PPI except for economic considerations. Direct comparison between omeprazole and lansoprazole for efficacy of H. pylori eradication has never been performed in an Israeli poplulation. Based on the pharmacokinetic data, lansoprazole-based therapy may be a better alternative than omeprazole-based therapy. The aim of this study was to compare the effectiveness of triple therapy regimens with omeprazole (Losec, AstraZeneca; or Omeradex, Dexxon) or lansoprazole (TAP Pharmaceuticals) in eradicating H. pylori infection. The database of the biggest health insurance provider in Israel was reviewed for all patients who received 1 week of treatment with omeprazole (n = 1293) or lansoprazole (n = 85) with additional amoxicillin and clarithromycin for H. pylori eradication in 2002. All patients underwent the ¹³C-urea breath test (¹³CUBT) for validation of eradication. A negative ¹³CUBT result was noted in 1026 of the patients treated with omeprazole (79.4%) and 61 treated with lansoprazole (71.8%). On logistic regression analysis, none of the confounding factors (sex, age, indication, chronic use of PPI, eradication protocol) were found to contribute to the discrimination between a negative (successful eradication) and a positive (failed eradication) ¹³CUBT. There is no statistically significant difference between omeprazole and lansoprazole as part of a PPI-based triple therapy for eradication of H. pylori.     

Effects of Helicobacter pylori infection on Zollinger-Ellison syndrome

Both Zollinger-Ellison syndrome (ZES) and Helicobacter pylori infection are major etiologic factors for peptic ulcer. The aim of this study was to investigate the effect of H. pylori infection on ZES with special reference to acid secretion. Sixteen patients with ZES were selected (median age, 59 years; range, 39–66 years; M/F, 9/7), and H. pylori status, ulcer location, gastric acid secretion, serum pepsinogen (PG) I and II concentrations, and PG I/II ratio were determined. The seroprevalence of H. pylori infection was 50%, whereas active H. pylori infection was seen in only 25% of the patients. Thirteen patients had duodenal ulcer (DU), 1 had gastric ulcer (GU), and 2 had both GU and DU. DU was seen in both H. pylori-positive and H. pylori-negative patients, whereas GU was found only in H. pylori-positive patients. Both basal and maximal acid outputs were significantly lower in H. pylori-positive patients than in H. pylori-negative patients (P < 0.05). Moreover, both serum PG I and the PG I/II ratio were significantly lower in H. pylori-positive patients than in H. pylori-negative patients. These results indicate that ZES is an independent risk factor for DU, but H. pylori infection may play some role in the development of GU in ZES. In patients with ZES, H. pylori infection may reduce both hypersecretion from parietal cells and PG I secretion from chief cells, and hyperacidity of the stomach in ZES may have eradicated H. pylori in some patients. Received: March 30, 2000 / Accepted: May 26, 2000     

Effect of Helicobacter pylori infection on cyclooxygenase‐2 expression in gastric antral mucosa

OBJECTIVE: Helicobacter pylori infection is a major etiological cause of chronic gastritis. Inducible cyclooxygenase (COX‐2) is an important regulator of mucosal inflammation. Recent studies indicate that expression of COX‐2 may contribute to gastro­intestinal carcinogenesis. The aim of this study was to investigate the effects of H. pylori infection and eradication therapy on COX‐2 expression in gastric antral mucosa. METHODS: Antral biopsies were taken from 46 H. pylori‐infected patients, who also had chronic gastritis, both before and after anti‐H. pylori treatment. The COX‐2 protein was stained by using immunohistochemical methods and COX‐2 expression was quantified as the percentage of epithelial cells expressing COX‐2. Gastritis and H. pylori infection status were graded according to the Sydney system. RESULTS: Cyclooxygenase‐2 expression was detected in the cytoplasm of gastric antral epithelial cells both before and after the eradication of H. pylori. Cyclooxygenase‐2 expression in mucosa with H. pylori infection was compared with the corresponding mucosa after successful H. pylori eradication (20.1 ± 13.1%vs 13.8 ± 5.9%; P < 0.05). At the same time, COX‐2 expression in H. pylori‐infected mucosa was com­pared with the normal controls (18.0 ± 14.1%vs 12.3 ± 4.6%, P < 0.05). Expression of COX‐2 was correlated with the degree of chronic inflammation (r= 0.78, P < 0.05). CONCLUSIONS: Our results showed that H. pylori infection leads to gastric mucosal overexpression of COX‐2 protein, suggesting that the enzyme is involved in H. pylori‐related gastric pathology in humans.