Assessing the severity of atrophic gastritis

Atrophic gastritis, mainly the consequence of long-standing Helicobacter pylori infection, is linked to the development of gastric cancer. In the case of atrophic gastritis, severity may be mainly related to the lifetime risk of the single patient to develop gastric cancer, mostly in relation to the degree and extension of mucosal damage. As atrophic gastritis is the result of complex multifactorial interactions, the application of artificial neural networks is promising and may be useful for the identification of those patients with atrophic gastritis at higher risk for gastric malignancies. The experience of application of artificial neural networks in atrophic gastritis is still scarce. The available data suggest that these systems may contribute to identify patients with corporal metaplastic atrophic gastritis and to optimize bioptic sampling during gastroscopy.     

慢性胃炎胃黏膜细胞DNA含量和增殖活性的流式细胞仪检测

背景慢性萎缩性胃炎是一种胃癌癌前状态,研究表明正常胃黏膜、癌前病变和胃癌细胞的DNA含量随病变的进展而逐渐增高。目的应用流式细胞仪检测慢性胃炎胃黏膜细胞的DNA含量和增殖活性,探讨两者在慢性胃炎发生、发展过程中的临床意义。方法选取90例经胃镜检查诊断为慢性胃炎者的胃黏膜活检标本,制备单细胞悬液,应用流式细胞仪进行细胞DNA含量和增殖活性检测。结果所有慢性胃炎胃黏膜细胞的DNA倍体类型均为二倍体,但慢性萎缩性胃炎和慢性萎缩性胃炎伴肠化生胃黏膜细胞的增殖指数(PI)较慢性非萎缩性胃炎显著增高(P<0.05)。除慢性非萎缩性胃炎外,其余慢性胃炎组幽门螺杆菌(H.pylori)阳性患者胃黏膜细胞的PI值均较阴性患者显著增高(P<0.05)。结论慢性萎缩性胃炎和H.pylori阳性慢性胃炎胃黏膜细胞的增殖活性显著增高。应用流式细胞仪检测胃黏膜细胞的DNA含量和增殖活性,也许能成为胃癌癌前状态和癌前病变病理诊断的参考指标。     

alkB基因在胃癌和萎缩性胃炎黏膜组织中的表达改变

背景:DNA或RNA分子异常甲基化导致的抑癌基因沉默、突变或其他功能性障碍是胃癌发生的关键机制之一。最近研究发现alkB基因产物具有修复DNA和mRNA碱基异常甲基化、纠正基因突变、复制转录障碍等功能,但对其在胃癌及其癌前病变组织中的表达情况尚不了解。目的:探讨alkB基因在胃癌及其癌前病变组织中的表达改变。方法:收集11例胃癌、癌旁和远离癌灶正常黏膜组织以及107例慢性萎缩性胃炎和121例非萎缩性胃炎患者的内镜活检黏膜,应用基因表达谱芯片实验评估alkB基因在各组织中的表达。以逆转录聚合酶链反应(RT-PCR)检验上述结果。结果:与远离癌灶正常黏膜组织相比,alkB基因在胃癌中的表达降低(Ratio值为0.208);与非萎缩性胃炎黏膜组织相比,alkB基因在萎缩性胃炎黏膜组织中的表达降低(Ratio值为0.378);而alkB基因在癌旁和远离癌灶正常黏膜组织中的表达无显著差异(Ratio值为0.726)。结论:alkB基因在胃癌和萎缩性胃炎黏膜组织中的表达下调,可能参与了胃癌发生过程中基因甲基化紊乱的机制。alkB基因是有潜在研究价值的分子靶标。     

萎缩性胃炎与非萎缩性胃炎胃黏膜基因表达谱的对照研究

目的 萎缩性胃炎是癌前疾病之一，常为非萎缩性胃炎演变的后果。应用生物芯片技术观察萎缩性胃炎和非萎缩性胃炎胃黏膜组织基因表达谱的差异，探讨萎缩性胃炎发生的分子生物学机制。方法 连续登记在门诊接受胃镜检查的萎缩性胃炎和非萎缩性胃炎患者227例，男143例，女84例，平均年龄48．6岁(16～72岁)。胃镜检查时获取胃体和胃窦黏膜活检标本进行病理学检查，其余活检黏膜组织液氮冻存。根据病理学检查结果将冻存的组织标本分成萎缩性胃炎组和非萎缩性胃炎组，分别抽提两组组织的总RNA，逆转录制备荧光cDNA探针，用含有8464条人类体细胞基因模板的表达谱cDNA芯片进行杂交实验。结果 与非萎缩性胃炎相比，萎缩性胃炎的活检胃黏膜组织中165项基因的表达水平上调2倍以上，460项的表达水平下调50％以上。表达下调者占73．6％。结论 基因表达谱生物芯片技术可以获得萎缩性胃炎胃黏膜组织基因在表达水平上改变情况的较全面的信息；萎缩性胃炎涉及多基因在表达水平上的改变。     

Metachronous gastric cancer after successful Helicobacter pylori eradication

The high incidence of gastric cancer in Japan initially resulted in establishment of a country-wide gastric cancer screening program to detect early and treatable cancers. In 2013 countrywide Helicobacter pylori (H. pylori) eradication was approved coupled with endoscopy to assess for the presence of chronic gastritis. Current data support the notion that cure of the infection in those with non-atrophic gastritis will prevent development of gastric cancer. However, while progression to more severe damage is halted in those who have already developed, atrophic gastritis/gastric atrophy remain at risk for subsequent development of gastric cancer. That risk is directly related to the extent and severity of atrophic gastritis. Methods to stratify cancer risk include those based on endoscopic assessment of the atrophic border, histologic grading, and non-invasive methods based on serologic testing of pepsinogen levels. Continued surveillance is required because those with atrophic gastritis/gastric atrophy retain considerable gastric cancer risk even after H. pylori eradication. Those who have already experienced a resectable early gastric cancer are among those at highest risk as metachronous lesions are frequent even after H. pylori eradication. We review the role of H. pylori and effect of H. pylori eradication indicating the incidence and the predictive factors on development of metachronous cancer after endoscopic therapy of early gastric cancer. Studies to refine risk markers to stratify for risk, surveillance methods, intervals, and duration after successful H. pylori eradication, and whether adjuvant therapy would change risk are needed.     

Atrophic gastritis is associated with increased sucrose permeability related to chronic inflammation

BACKGROUND: Different theories have been presented to explain how atrophic gastritis may lead to gastric cancer development. One contributing factor could be impaired function of the gastric mucosal barrier. The aim of this study was to investigate if there are changes in gastric mucosal permeability to sucrose in atrophic gastritis. METHODS: The study comprised 22 patients with atrophic gastritis and 21 normal controls. Gastritis was classified according to the Sydney system from endoscopic biopsies of the gastric corpus and antrum. All subjects were exposed to oral sucrose load (100 g), and the fraction of sucrose excreted in urine was measured by gas chromatography-mass spectrometry. RESULTS: The fraction of sucrose excreted in urine after oral load was significantly increased in atrophic gastritis compared with controls (median 0.08 vs. 0.04%; p = 0.003). Sucrose excretion was positively related to the degree of chronic inflammation (median fraction excreted: mild inflammation 0.06%, moderate inflammation 0.08%, severe inflammation 0.18%; p = 0.04) rather than to the degree of atrophy in the gastric mucosa. Occurrence of intestinal metaplasia was also associated with significantly higher sucrose excretion. However, in multivariate analysis, including intestinal metaplasia, only the degree of inflammation was positively related to sucrose excretion. CONCLUSION: Atrophic gastritis is associated with increased sucrose permeability, suggesting paracellular leakage of the gastric mucosa. This leakage seems to be related to the degree of inflammation rather than the degree of atrophy. The findings may have implications for the diseases and complications associated with atrophic gastritis.     

Nucleotide-binding oligomerization domain 1 and Helicobacter pylori infection: A review

Nucleotide-binding oligomerization domain 1(NOD1) is an intracellular innate immune sensor for small molecules derived from bacterial cell components. NOD1 activation by its ligands leads to robust production of pro-inflammatory cytokines and chemokines by innate immune cells, thereby mediating mucosal host defense systems against microbes. Chronic gastric infection due to Helicobacter pylori(H. pylori) causes various upper gastrointestinal diseases, including atrophic gastritis, peptic ulcers, and gastric cancer. It is now generally accepted that detection of H. pylori by NOD1 expressed in gastric epithelial cells plays an indispensable role in mucosal host defense systems against this organism. Recent studies have revealed the molecular mechanism by which NOD1 activation caused by H. pylori infection is involved in the development of chronic gastritis and gastric cancer. In this review, we have discussed and summarized how sensing of H. pylori by NOD1 mediates the prevention of chronic gastritis and gastric cancer.     

Bcl-2和Bax在胃癌中的表达及其意义

背景：细胞凋亡异常在肿瘤发生中起重要作用,抑凋亡基因Bcl-2和促凋亡基因Bax与细胞凋亡密切相关。目的：探讨Bcl-2和Bax在胃癌中的表达及其意义。方法：采用免疫组化SP法检测30例慢性非萎缩性胃炎、30例慢性萎缩性胃炎和30例胃癌黏膜组织中Bcl-2和Bax表达水平。结果：慢性非萎缩性胃炎组Bcl-2和Bax表达阳性率与慢性萎缩性胃炎组相比无明显差异（Bcl-2：36．7％对43．3％,Bax：33．3％对50．0％,P〉0．05）,但均显著低于胃癌组（分别为66．7％和80．0％,P〈0．05）。结论：Bcl-2和Bax在胃癌中的表达明显增加,提示两者可能在胃癌的发生、发展中起重要作用。     

Overexpression of peroxisome proliferator‐activated receptor γ and retinoid X receptor α in gastric carcinomatous tissue

OBJECTIVE: To investigate the expression of peroxisome proliferator‐activated receptor γ (PPAR‐γ) and retinoid X receptor α (RXR‐α) in chronic gastritis, gastric mucosal dysplasia and gastric carcinoma and to identify any correlations between PPAR‐γ and RXR‐α expression in this progression sequence. METHODS: Immunohistochemical methods (avidin? biotin?peroxidase complex) were used to examine the expression of PPAR‐γ and RXR‐α in 53 patients with gastric carcinoma, 18 with gastric mucosal dysplasia and 30 with chronic atrophic gastritis. Thirty‐one patients with chronic non‐atrophic gastritis acted as controls. RESULTS: The positive rates of PPAR‐γ and RXR‐α in gastric carcinoma were 41.5 and 54.7%, 27.8 and 38.9% in gastric mucosal dysplasia, 10.0 and 20.0% in chronic atrophic gastritis, and 6.5 and 16.1% in chronic non‐atrophic gastritis, respectively. The expression of PPAR‐γ and RXR‐α increased during the progression from chronic non‐atrophic gastritis to chronic atrophic gastritis, then to gastric carcinoma. Compared with chronic gastritis, the expression of PPAR‐γ and RXR‐α in gastric mucosal dysplasia and gastric carcinoma was significantly increased (P < 0.05, P < 0.01). In gastric carcinoma, the expression of PPAR‐γ and RXR‐α was not associated with tumor cell differentiation or metastasis in the lymph nodes (P > 0.05). There was a positive correlation between the expression of PPAR‐γ and RXR‐α in gastric carcinoma (r= 0.54, P < 0.01). CONCLUSIONS: Overexpression of PPAR‐γ and RXR‐α protein is apparent in human gastric cancer. This might be an early event in carcinogenesis, and both PPAR‐γ and RXR‐α may play independent and/or synergistic roles in the progression of gastric carcinoma.     

Possibility of non-invasive diagnosis of gastric mucosal precancerous changes

AIM: To assess the possibility of non-invasive screening of atrophic chronic gastritis for preventing further development of gastric cancer. METHODS: One hundred and seventy-eight consecutive Helicobacter pylori (H pylori)-positive dyspeptic patients after detection of serum levels of pepsinogen-1 (PG-1) and gastrin-17 (G-17) by enzyme immunoassay were proposed for endoscopy and histology. The serologic and morphologic results were compared with estimating the sensitivity, specificity and prognostic values of the tests. RESULTS: There was statistically significant reverse dependence between the grade of stomach mucosal antral or corpus atrophy and the proper decreasing of serum G17 or PG1 levels. The serologic method was quite sensitive in the diagnosis of non-atrophic and severe antral and corpus gastritis. Also, it was characterized by the high positive and negative prognostic values. CONCLUSION: Detection of serum G-17 and PG1 levels can be offered as the screening tool for atrophic gastritis. The positive serologic results require further chromoendoscopy with mucosal biopsy, for revealing probable progressing of atrophic process with development of intestinal metaplasia, dysplasia or gastric cancer.     

胃黏膜癌变过程中表皮生长因子受体、环氧合酶-2和三叶因子1的表达及其意义

胃黏膜癌变过程中存在癌基因激活和抑癌基因失活所致的细胞无限增殖和凋亡抑制，因此联合检测细胞增殖和凋亡相关因子对揭示胃黏膜的变化规律具有重要意义。目的：探讨表皮生长因子受体（EGFR）、环氧合酶（COX）．2和三叶因子（TFF）1在胃黏膜癌变过程中的变化规律及其意义。方法：经病理检查确诊的19例慢性非萎缩性胃炎、19例慢性萎缩性胃炎、18例慢性萎缩性胃炎伴肠化生、16例异型增生和16例胃腺癌纳入研究。以免疫组化方法检测各病变组织中EGFR、COX-2和TFF1的表达，并分析其间的相关性。结果：EGFR在非萎缩性胃炎组织中的表达显著低于其他胃黏膜病变组织（P〈0．01）；从非萎缩性胃炎→萎缩性胃炎→肠化生→异型增生→胃癌，COX-2的表达逐渐增高，而TFF1的表达逐渐减低。EGFR与COX-2的表达呈正相关（P〈0．01），与TFF1的表达呈负相关（P〈0．01）：COX-2与TFF1的表达呈负相关（P〈0．01）。结论：细胞增殖和凋亡相关因子EGFR、COX-2和TFF1表达异常在胃黏膜癌变过程中发挥重要作用。     

Präneoplastische Bedingungen des Magens

Gastric cancer is one of the most common cancers in the world and is associated with a high mortality. Noncardia gastric cancer usually develops through a cascade of mucosal changes from nonatrophic gastritis to atrophic gastritis, intestinal metaplasia, dysplasia, and adenocarcinoma. Atrophic gastritis and intestinal metaplasia are therefore considered as preneoplastic conditions in the stomach. The etiology of atrophic gastritis is based on Helicobacter pylori infection and/or autoimmune gastritis. H. pylori eradication therapy offers the unique chance to prevent gastric cancer and to improve preneoplastic conditions of the stomach. Eradication therapy should be offered at the earliest stage with the goal to interrupt the cascade leading to gastric cancer. Patients with preneoplastic conditions of the stomach should be monitored using clinically meaningful endoscopic surveillance strategies. This review focuses on preneoplastic conditions of the stomach, therapeutic options, and possible surveillance strategies.     

Gastric Emptying and Dyspeptic Symptoms in Patients with Nonautoimmune Fundic Atrophic Gastritis

Our aim was to evaluate the relationship between gastric emptying and demographic, clinical, histological, and secretory features in patients with nonautoimmune fundic atrophic gastritis. Only 31% of 45 patients with fundic atrophic gastritis presented with achlorhydria. Scintigraphic gastric emptying of solids was delayed compared to healthy controls. Patients with achlorhydria showed gastric emptying rates lower than those with preserved acid secretion. Significant, but weak, correlations were observed between emptying rates and both peak acid output (Rs = 0.33) and serum gastrin levels (Rs = –0.36), but not with grading of mucosal atrophy. No symptom differences were observed between patients with or without achlorhydria, but a weak correlation was detected between peak acid output and the severity of epigastric pain (Rs = 0.40). In conclusion, patients with fundic atrophic gastritis present delayed gastric emptying that is weakly related to the reduction of the acid secretion and the raising of serum gastrin levels rather than to the severity of the atrophy.     

幽门螺杆菌相关性胃病的细胞增殖和凋亡

目的 观察幽门螺杆菌（Hp)及其CagA基因对细胞增殖和凋亡的影响,进而探讨Hp增加胃癌发生危险性的机制。方法 研究对象为慢性浅表性胃炎（CSG）、慢性萎缩性胃炎（CAG）、慢性萎缩性胃炎伴肠上皮化生（CAGIM）、不典型增生（DYS）、胃癌（GC）患者127例及正常对照组（NS）14例。应用ki-67免疫组化技术评价幽门窦上皮细胞增生,用切口末端标记法（TUNEL）检测胃上皮细胞凋亡,应用聚合酶链反应（PCR）技术检测Hp的CagA基因。结果 Hp阳性患者的增殖指数（LI）和凋亡指数（AI）显著高于Hp阴性者或正常对照（P＜0．05和P＜0．01）。CSGHp阳性的LI和AI明显高于Hp阴性者（P＜0．01）,而其余四种胃病Hp阳性患者（P＜0．05）。Hp阳性或阴性CSG、NS组的AI与LI呈正相关,GC患者的AI与LI呈负相关。LI和AI与胃粘膜炎症程度无明显关系。结论 Hp诱导胃粘膜上皮细胞过度增殖和凋亡主要发生在Hp感染的早期,CagA^ Hp与CagA^－Hp促增殖和凋亡作用的能力明显不同,Hp感染通过引起增殖和凋亡比例的失调,最终促进肿瘤发生。     

Advanced gastric cancer of the antrum: Anatomic-functional correlation between chief cell mass and serum pepsinogen I

Chief cell mass and type I serum pepsinogen (PGI) were calculated in 19 advanced antral gastric cancer of intestinal type. Comparisons were also made with parietal cell mass and acid secretion. In gastric cancer of the antrum there is a significant decrease of the chief cell mass and of serum pepsinogen I. The patients were subdivided according to the histological findings of the fundic mucosa. In cases of antral gastric cancer with superficial fundic gastritis there is normozymogenism with hyperpepsinogenemy; with preatrophic fundic gastritis there is hypozymogenism with normopepsinogenemy; with atrophic fundic gastritis there is hypozymogenism with hypopepsinogenemy. Similar behavior of the chief cell mass between antral gastric cancer and fundic atrophic gastritis without cancer has become recognized and while the validity of PGI as a marker of fundic atrophic gastritis has emerged it does not allow discrimination between atrophic fundic gastritis and atrophic fundic gastritis associated with gastric cancer of the antrum.     

Non-invasive tests in gastric diseases

Although the gastric cancer incidence is decreasing, this neoplasia remains one of the major causes of oncological mortality. Because of an insidious development, gastric cancer is often diagnosed in an advanced stage and consequently with a poor prognosis. Accurate non-invasive tests should be extremely useful in order to detect gastric neoplasm in an early phase. In clinical practice, there is no reliable bio-marker for detecting this malignant disease. However, intestinal as well as diffuse types of gastric cancer are preceded by gastric mucosa inflammation. Furthermore, the intestinal type of the neoplasia is, generally, related to chronic atrophic gastritis, especially if associated with intestinal metaplasia. In particular, the risk of the neoplasm is linked to both extension and severity of gastric atrophy. Serological parameters such as serum pepsinogens I (PGI) and II (PGII), gastrin-17 (G-17) cytokines (e.g. IL-8), antiparietal cells, IgG anti-Hp and CagA antibodies and lastly ghrelin supply information about either atrophic or inflammatory conditions characterising gastric mucosa. Low PGI and PGI/PGII ratio levels, especially if combined with high G-17 levels, are recognised bio-markers of corpus atrophic gastritis. Low G-17 levels could be, also, suggestive of antral atrophic gastritis. Furthermore, plasmatic ghrelin levels seem to be also a bio-marker of corpus atrophy. Anti-Hp IgG and CagA antibodies as well as PGII levels are able to detect gastric inflammation. Serological parameters could select subjects at risk for gastric mucosa alterations such as inflammation or atrophy, rather than gastric cancer itself. This review analyses the information derived from serological bio-markers as well as the involved clinical studies.     

Feasibility and cost-effectiveness of using magnification chromoendoscopy and pepsinogen serum levels for the follow-up of patients with atrophic chronic gastritis and intestinal metaplasia

BACKGROUND: The follow-up of patients with atrophic chronic gastritis or intestinal metaplasia may lead to early diagnosis of gastric cancer. However, to-date no cost-effective model has been proposed. Improved endoscopic examination using magnification chromoendoscopy together with non-invasive functional assessment with pepsinogen serum levels are accurate in the diagnosis of intestinal metaplasia (extension) and minute dysplastic lesions. The aim of this study was to assess the feasibility and cost-effectiveness of a follow-up model for patients with atrophic chronic gastritis and intestinal metaplasia based on gastric mucosal status using magnification chromoendoscopy and pepsinogen. METHODS: A cohort of patients with lesions as severe as atrophic chronic gastritis were followed-up according to a standardized protocol using magnification chromoendoscopy with methylene blue and measurement of serum pepsinogen I and II levels. A single node decision tree and Markov chain modeling were used to define cost-effectiveness of this follow-up model versus its absence. Transition rates were considered time-independent and calculated using primary data following cohort data analysis. Costs, quality of life and survival were estimated based on published data and extensive sensitivity analysis was performed. RESULTS: A total of 100 patients were successfully followed-up over 3 years. Seven cases of dysplasia were diagnosed during follow-up, all among patients with incomplete intestinal metaplasia at baseline, six of whom had extensive (pepsinogen I to II ratio <3) incomplete intestinal metaplasia. For those individuals with atrophic chronic gastritis or complete intestinal metaplasia, a yearly measurement of pepsinogen levels or an endoscopic examination on a 3-yearly basis would cost 455 euros per quality-adjusted life year (QALY) gain. Endoscopic examination and pepsinogen serum level measurement on a yearly basis would cost 1868 euros per QALY for patients with extensive intestinal metaplasia. CONCLUSIONS: The follow-up of patients with atrophic chronic gastritis or intestinal metaplasia is both feasible and cost-effective if improved accurate endoscopic examination of gastric mucosa together with non-invasive assessment of gastric mucosal status are used to identify individuals at high-risk for development of gastric cancer.     

Helicobacter pylori-associated gastritis and gastric cancer in Nigeria.

BACKGROUND: The etiology of gastric cancer has not been clearly delineated. There is some evidence of an association of gastric cancer with Helicobacter pylori-induced chronic gastritis, atrophic gastritis and intestinal metaplasia. Previous studies report a high rate of H. pylori infection and chronic gastritis among Nigerians. METHODS: We retrospectively reviewed 84 tissue specimens with gastric cancer seen in our department over an 18-year period for for the presence of H. pylori infection, chronic gastritis, atrophic gastritis, and intestinal metaplasia in the adjacent non-cancerous gastric mucosa. RESULTS: H. pylori infection was detected in 15 (17.9%) of 84 specimens. Moderate to severe gastritis was found in non-cancerous areas in 77 (91.7%) specimens, and was equally frequent in patients with 'intestinal' and 'diffuse' types of cancer. Atrophic gastritis and intestinal metaplasia were observed in 22 (26.2%) and 35 (41.7%) specimens, respectively, and were more common in 'intestinal' type of gastric cancer. CONCLUSION: Chronic gastritis was seen in the adjacent non-cancerous mucosa in most specimens with gastric cancer. However, its severity did not correlate with the histological subtype of gastric cancer.     

Changes in arterioles of the human gastric mucosa with atrophic gastritis

Arteriolar changes in the gastric mucosa of 18 patients with atrophic gastritis and of 13 control subjects without atrophic gastritis were investigated using electron microscopy. Irregularly configured smooth muscle cell atrophy with lysosomes and interstitial deposition of highly electron dense material were found in mucosal arterioles of the patients with atrophic gastritis. These findings were similar to the findings seen in patients with hypertension, and animals with experimentally-induced hypertension. Similar, but mild, changes were also noted in mucosal arterioles of control subjects. However, such findings were more common in the aged. These results suggest that the arteriolar changes in the gastric mucosa represent fundamental factors causing atrophic gastritis.