胃粘膜肠上皮化生的内镜分析

目的探讨内镜下胃粘膜肠上皮化生诊断的可行性及准确度。方法应用放大或普通型内镜对受检者的胃底、胃体及胃窦进行仔细观察,详细描述肠上皮化生的表现特点并至少于胃窦小弯、大弯及胃体各取活组织检查(简称活检)一块,收集同期病理诊断肠上皮化生的病例并将内镜表现与病理进行对照分析。结果同期病理组织学诊断肠上皮化生患者329例。根据内镜下的特异性肠上皮化生的表现淡黄色结节型、瓷白色小结节型、鱼鳞型和弥漫型,内镜诊断肠上皮化生134例,经活检病理证实128例,内镜诊断符合率95.5％。胃粘膜活检诊断而内镜未予诊断者201例,内镜检查诊断肠上皮化生的总符合率38.9％。轻、中、重度肠上皮化生内镜诊断率不同,分别为23.8％、48.5％和51.7％。而放大内镜对轻、中、重度肠上皮化生诊断准确率分别为47.5％、78.5％和75.4％,明显高于普通型内镜组的14.9％、28.6％和34.9％,差异有显著性(P＜0.05)。结论胃粘膜肠上皮化生内镜表现除淡黄色结节型和弥漫型外,尚有鱼鳞型和瓷白色小结节型,这四种典型的肠上皮化生形态学特征,是内镜诊断肠上皮化生的特异型标志。这四种肉眼形态学特征与病理肠上皮化生程度无关,但肠上皮化生程度与内镜诊断呈平行关系。放大内镜对肠上皮化生诊断率明显高于普通型内镜。     

胃粘膜萎缩与肠化的细胞增殖和凋亡研究

目的研究胃粘膜萎缩和广泛肠化的细胞增殖与凋亡的定量关系.方法 CSG 14例,CAG11例,CAG+IM 20例,对照5例,分别作HE染色,ISEL检测细胞凋亡,免疫组化PCNA和bcl-2抗体染色.求各组增殖指数(PI)、凋亡指数(AI)、凋亡增殖比和凋亡强度.结果各组PI和AI分别是:15.4%,24.8%,56.9%和8.4%,5.4%,11.6%,1.9%和1.4%;在CSG,CAG凋亡和增殖呈正相关(r=0.5475和0.5839),CAG凋亡强度最大;CAG+IM PI最高,但凋亡和增殖呈负相关(r=-0.6742),凋亡强度异常低,不足对照组的1/5,CSG的1/10,CAG的1/14.结论 CAG的萎缩可能是过度凋亡所致;CAG+IM则出现凋亡障碍,过度增殖,与异型增生和癌的细胞生物学表现相似.     

根除幽门螺杆菌对胃黏膜萎缩并肠上皮化生以及COX-2、C- met表达的影响

目的研究幽门螺杆菌(helicobacter pylori,Hp)根除前后胃黏膜萎缩和肠上皮化生的变化以及环氧合酶-2(cyclooxygenase-2,COX-2)和肝细胞生长因子受体(C-met)的表达。方法 13例患者均为胃镜加病理确诊有萎缩并肠化生合并HP感染,且成功根除HP感染者。用免疫组化方法半定量检测HP除前后萎缩性胃炎并肠上皮化生COX-2蛋白和C-met蛋白的表达。结果根除前和根除后1个月萎缩程度积分分别为1.3±0.3,1.2±0.7,根除后1个月与根除前比较无显著差异(P>0.05)。萎缩并肠化生胃黏膜C-met平均阳性细胞率从根除前53.2±12.4％下降至根除后48.8±7.7％,比较有显著差异(P=0.034)。胃黏膜COX-2平均阳性细胞率从根除前36.5±14.0％下降至根除后23.3±7.9％,有显著差异(P=0.023)。COX-2表达与C-met表达有一定的相关性(r=0.310,P<0.05)。结论 HP根除短期内不能逆转胃黏膜萎缩,但可使慢性萎缩性胃炎胃黏膜中COX-2和C-met癌基因表达下降。COX-2表达与C-met表达相关。     

Prevalence of subtypes of intestinal metaplasia in gastric antral mucosa

A prospective gastroscopic-bioptic study of 533 patients was performed to assess the prevalence and distribution of intestinal metaplasia (IM) and its subtypes in the antral mucosa of patients with various upper intestinal disorders and to assess whether the presence of certain IM subtypes might be of help in selecting patients for careful endoscopic-bioptic surveillance in the screening for gastric carcinoma. IM was found in 135 patients (25.3%). Its prevalence increased with age (P<0.001) and was strongly associated with intestinal-type carcinoma as compared to diffuse-type carcinoma (P<0.001), gastritis (P<0.001), and gastric ulcer (P<0.05). Type I IM was predominant (98.5%), whereas types II and III IM, respectively, were found in 77.8% and 15.6% of the patients with IM. No difference in the prevalence of type I and II IM was found among the various gastric disease states. Type III IM was strongly associated with intestinal-type carcinoma as compared to either benign lesions (P<0.01) or diffuse-type carcinoma. These results suggest that type III IM may play a special role in the histogenesis of intestinal-type carcinoma and suggest that the finding of this IM subtype in gastric biopsies may possibly be of help in identifying patients at greater risk of developing carcinoma.     

Heterotopic gastric mucosa with focal intestinal metaplasia and squamous epithelium in the rectum

Heterotopic gastric mucosa has been described in all levels of the gastrointestinal tract. However, gastric heterotopia of the rectum is a rare finding. It is usually reported along with polyp located in the rectum between 5 and 8 cm from the anal verge. The most common symptom is painless rectal bleeding, and non-specific gastrointestinal symptoms may also be presented. We report an incidentally found case of a 46-year-old man without any gastrointestinal symptoms. The pathology showed gastric mucosa and squamous epithelium and focal intestinal metaplasia. This finding could be a clue as to the origins of the heterotopic gastric mucosa. Although there are no guidelines for treatment or the follow-up period, regular endoscopic surveillance is necessary for gastric cancer screening.     

Gastric microbiota in patients with Helicobacter pylori-negative gastric MALT lymphoma

To investigate the mucosal microbiota in the stomach of patients with Helicobacter pylori-negative mucosa-associated lymphoid tissue (MALT) lymphoma by means of metagenomic analysis.Although some gastric MALT lymphomas are associated with the presence of H. pylori, other gastric MALT lymphomas occur independently of H. pylori infection. The pathogenesis of H. pylori-negative MALT lymphoma remains unclear.Mucosal biopsy specimens were collected from the gastric body from 33 MALT lymphoma patients with gastric lesions, including both H. pylori-infection naïve patients and posteradication patients, as well as 27 control participants without H. pylori infection or cancer. Subsequently, the samples were subjected to 16S rRNA gene sequencing. Quantitative insights into microbial ecology, linear discriminant analysis effect size, and phylogenetic investigation of communities by reconstruction of unobserved states softwares were used to analyze the participants’ microbiota.H. pylori-negative MALT lymphoma patients had significantly lower alpha diversity (P = .04), compared with control participants. Significant differences were evident in the microbial composition (P = .04), as determined by comparison of beta diversity between the 2 groups. Taxonomic composition analysis indicated that the genera Burkholderia and Sphingomonas were significantly more abundant in MALT lymphoma patients, while the genera Prevotella and Veillonella were less abundant. Functional microbiota prediction showed that the predicted gene pathways “replication and repair,” “translation,” and “nucleotide metabolism” were downregulated in MALT lymphoma patients.H. pylori-negative MALT lymphoma patients exhibited altered gastric mucosal microbial compositions, suggesting that altered microbiota might be involved in the pathogenesis of H. pylori-negative MALT lymphoma.     

Cyclooxygenase-2 expression is increased in early intestinal-type gastric cancer and gastric mucosa with intestinal metaplasia

OBJECTIVE: Cyclooxygenase-2 (COX-2) expression is increased in gastric cancer. We examined COX-2 expression in early stage gastric cancer and background mucosa to elucidate the role of COX-2 in gastric carcinogenesis. METHODS: Thirty-three early gastric cancers obtained from 30 patients infected with Helicobacter pylori were studied. Twenty-three patients had an intestinal, four patients had a diffuse, and three patients had both an intestinal and a diffuse type cancer. Expression of COX-2 protein was detected by immunohistochemistry by counting the number of positive staining cells per 100 cells. RESULTS: Mean COX-2 expression was 84.1 (SD 11.4) in 26 intestinal type cancers and was significantly higher than that in seven diffuse type cancers (23.1 +/- 9.7) (P < 0.001). In three patients who had both the intestinal and the diffuse type cancer, COX-2 expression was 92, 90 and 83 in the intestinal type cancer and only 25, 24 and 7 in the corresponding diffuse type cancer. In 18 patients who had intestinal metaplasia (15 had incomplete metaplasia), COX-2 expression was 60.2 (24.2) in the crypts with metaplasia while it was only 16.8 (10.7) in the crypts without metaplasia (P < 0.001). CONCLUSIONS: COX-2 expression may be associated with the carcinogenesis of the intestinal type gastric cancer and, speculatively, inhibition of COX-2 might have preventative effects on the intestinal type gastric cancer.     

Adenocarcinoma risk in gastric atrophy and intestinal metaplasia: a systematic review

Background

Gastric cancer (GC) has a poor prognosis with wide variation in survival rates across the world. Several studies have shown premalignant lesions gastric atrophy (GA) and intestinal metaplasia (IM) influence gastric cancer risk. This systematic review examines all available evidence of the risk of GC in patients with GA or IM and explores the geographical variation between countries.

Methods

EMBASE, MEDLINE, Web of Science and the Cochrane Library were searched for relevant articles published to June 2016 investigating the risk of GC in individuals with GA or IM. Analysis was performed to determine variation based on geographical location. Study quality was assessed using the Newcastle-Ottawa Scale and heterogeneity between studies was also evaluated.

Results

Fifteen relevant articles were identified, in which there were eight studies of GC incidence in GA and nine in IM cohorts (two articles investigated both GA and IM). The incidence rate of GC in patients with GA ranged from 0.53 to 15.24 per 1000 person years, whereas there was more variation in GC incidence in patients with IM (0.38 to 17.08 per 1000 person years). The greatest GC incidence rates were in Asian countries, for patients with GA, and the USA for those with IM (15.24 and 17.08 per 1000 person years, respectively). The largest studies (four over 25,000 person years) had an incidence rate range of 1.0–2.5 per 1000 person years, however, in general, study quality was poor and there was marked heterogeneity.

Conclusion

Overall there is a wide variation in annual incidence rate of GC from premalignant lesions. With the recent introduction of surveillance guidelines for gastric atrophy and intestinal metaplasia in the Western world, future assessment of this risk should be performed. Furthermore, substantial heterogeneity supports the need for more robust studies in order to pool results and determine the overall incidence rate of gastric cancer for patients with these premalignant lesions.

     

胃黏膜肠上皮化生内镜诊断和分级的研究进展

胃黏膜肠上皮化生（gastric intestinal metaplasia,GIM）是一种癌前组织病理学改变,其临床意义在于对胃癌发生风险的提示,有着大面积肠上皮化生背景的胃黏膜具有较高的癌变风险;另外,不完全型GIM与肠型胃癌相关。因此,GIM的内镜下监测对及时发现和管理早期胃癌具有重要意义。可操作的GIM胃癌风险评估分级提供了较好地针对肠上皮化生的胃黏膜癌变风险评估,但每次评估需要标准的活检,增加了损伤风险,GIM内镜分级在此背景下被提出,但其应用受内镜诊断GIM的准确性和临床使用的便捷性所制约。笔者分析了各类内镜下诊断技术对GIM的诊断效果,结合人工智能辅助识别GIM面积,综述EGGIM评分的可行性。     

Relationship between β-catenin expression and epithelial cell proliferation in gastric mucosa with intestinal metaplasia

AIM: To investigate beta-catenin expression in patients with intestinal metaplasia, and to look for a possible relationship between beta-catenin expression and either epithelial proliferation values or Helicobacter pylori (H pylori) infection. METHODS: Twenty patients with complete type intestinal metaplasia were studied. beta-Catenin expression and epithelial cell proliferation in antral mucosa were assessed using an immunohistochemical analysis. H pylori infection was detected by histology and a rapid urease test. RESULTS: Reduced beta-catenin expression on the surface of metaplastic cells was detected in 13 (65%) out of 20 patients. Moreover, in eight (40%) patients intranuclear expression of beta-catenin was found. When patients were analyzed according to H pylori infection, the prevalence of both beta-catenin reduction at the cell surface and its intranuclear localization did not significantly differ between infected and uninfected patients. Cell proliferation was higher in patients with intranuclear beta-catenin expression as compared to the remaining patients, although the difference failed to reach the statistical significance (36+/-8.9 vs 27.2+/-11.4, P = 0.06). On the contrary, a similar cell proliferation value was observed between patients with reduced expression of beta-catenin on cell surface and those with a normal expression (28.1+/-11.8 vs 26.1+/-8.8, P = 0.7). H pylori infection significantly increased cell proliferation (33.3+/-10.2% vs 24.6+/-7.4%, respectively, P = 0.04). CONCLUSION: Both cell surface reduction and intranuclear accumulation of beta-catenin were detected in intestinal metaplasia. The intranuclear localization of beta-catenin increases cell proliferation. H pylori infection does not seem to play a direct role in beta-catenin alterations, whilst it significantly increases cell proliferation.     

Relationship between p-catenin expression and epithelial cell proliferation in gastric mucosa with intestinal metaplasia

AIM: To investigate β-catenin expression in patients with intestinal metaplasia, and to look for a possible relationship between β-catenin expression and either epithelial proliferation values or Helicobacter pylori (H pylori) infection. METHODS: Twenty patients with complete type intestinal metaplasia were studied. β-Catenin expression and epithelial cell proliferation in antral mucosa were assessed using an immunohistochemical analysis. H pylori infection was detected by histology and a rapid urease test. RESULTS: Reduced β-catenin expression on the surface of metaplastic cells was detected in 13 (65%) out of 20 patients. Moreover, in eight (40%) patients intranuclear expression of β-catenin was found. When patients were analyzed according to H pylori infection, the prevalence of both β-catenin reduction at the cell surface and its intranuclear localization did not significantly differ between infected and uninfected patients. Cell proliferation was higher in patients with intranuclear β-catenin expression as compared to the remaining patients, although the difference failed to reach the statistical significance (36±8.9 vs27.2±11.4, P=0.06). On the contrary, a similar cell proliferation value was observed between patients with reduced expression of β-catenin on cell surface and those with a normal expression (28.1±11.8 vs26.1±8.8, P= 0.7). H pylori infection significantly increased cell proliferation (33.3±10.2% vs 24.6±7.4%, respectively, P=0.04). CONCLUSION: Both cell surface reduction and intranuclear accumulation of β-catenin were detected in intestinal metaplasia. The intranuclear localization of β-catenin increases cell proliferation. H pylori infection does not seem to play a direct role in β-catenin alterations, whilst it significantly increases cell proliferation.     

Long-term monitoring of gastric atrophy and intestinal metaplasia after Helicobacter pylori eradication

Improvements of atrophy and intestinal metaplasia which is seen after H. pylori eradication may be regarded as an important factor of gastric cancer prevention. Although many studies reported the alteration of gastric mucosa after H. pylori eradication, most of the results do not agree. Recently, two meta-analyses showed significant improvement of atrophy (one study showed improvement in both corpus and antrum, and the other showed improvement in corpus but not in antrum), whereas improvement of intestinal metaplasia was not shown in either corpus or antrum. However, one reason why conclusions are different is considered to be that the observation period after eradication was short, and another reason is considered to be that almost studies examined only two points in gastric mucosa for histological analysis. Further examination with a greater number of subjects and with longer follow up period should be required to clarify the mechanism of gastric injury and improvement of gastric mucosa, especially atrophy and intestinal metaplasia after H. pylori eradication.     

Decreased frequency of HLA-B35 in patients with gastric MALT lymphoma

Persistent infection with Helicobacter pylori has been shown to be strongly associated with the development of low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma. However, the prevalence of H. pylori infection exceeds the incidence of MALT lymphoma by far. This discrepancy might at least partially be explained on a genomic basis of the host. To evaluate the association between HLA type and MALT lymphoma, we investigated 46 patients with MALT lymphoma recruited in a prospective multicenter study from October 1998 to March 2001. Over 13,000 voluntary stem cell donors from over 40 German blood banks represented the control group. Exploratory statistical analysis using Fishers exact test showed significantly decreased frequency of HLA-B35 in the MALT lymphoma group compared to the control group. Our data suggest a negative association between HLA-B35 and MALT lymphoma; however, larger studies are necessary to confirm a protective role of this HLA antigen.     

共聚焦内镜对胃黏膜肠上皮化生的诊断价值

目的确定胃黏膜肠上皮化生的共聚焦内镜下形态学特征，探讨其组织学诊断价值。方法应用共聚焦内镜对78例患者进行常规胃镜检查，标准位置及有黏膜可疑病变部位用共聚焦内镜观察，制定共聚焦内镜下肠上皮化生的判定标准，与相应部位活检的病变组织的病理学检查结果进行比较分析。结果对患者的483个位置进行共聚焦扫描，获得12497幅图像，共聚焦内镜可以获得在体的胃小凹、上皮细胞、结缔组织和微血管网的高清晰的荧光图像，与病理一致。杯状细胞有特异的形态学特征，易于识别。43位患者的165块活检组织经病理确诊为肠上皮化生，其中普通内镜诊断50处，共聚焦内镜诊断163处，共聚焦内镜对肠上皮化生诊断明显优于普通内镜，其敏感性、特异性和准确性分别为98．79％，98．43％和98．76％。结论共聚焦内镜是一种全新的诊断工具，可以在内镜检查同时进行活体的虚拟组织学诊断，是准确诊断肠上皮化生的一种新方法。