Determination of an Appropriate Endoscopic Monitoring Interval for Patients with Gastric Precancerous Conditions in China

Objective Gastric precancerous conditions such as atrophic gastritis(AG)and intestinal metaplasia(IM)are considered independent risk factors for gastric cancer(GC).The suitable endoscopic monitoring interval is unclear when we attempt to prevent GC development.This study investigated the appropriate monitoring interval for AG/IM patients.Methods Totally,957 AG/IM patients who satisfied the criteria for evaluation between 2010 and 2020 were included in the study.Univariate and multivariate analyses were used to determine the risk factors for progression to high-grade intraepithelial neoplasia(HGIN)/GC in AG/IM patients,and to determine an appropriate endoscopic monitoring scheme.Results During follow-up,28 AG/IM patients developed gastric neoplasia lesions including gastric low-grade intraepithelial neoplasia(LGIN)(0.7%),HGIN(0.9%),and GC(1.3%).Multivariate analysis identified H.pylori infection(P=0.022)and extensive AG/IM lesions(P=0.002)as risk factors for HGIN/GC progression(P=0.025).Conclusion In our study,HGIN/GC was present in 2.2%of AG/IM patients.In AG/IM patients with extensive lesions,a 1–2-year surveillance interval is recommended for early detection of HIGN/GC in AG/IM patients with extensive lesions.

Genetic predisposition to Helicobacter pylori-induced gastric precancerous conditions

Gastric cancer is the most common malignancy of the gastrointestinal tract in East Asian populations and the second most frequent cause of cancer-related mortality in the world. While previous studies have investigated the genetic factors involved in gastric carcinogenesis, there still exist relatively few studies that have investigated the genetic traits associated with the risk of gastric precancerous conditions. In this paper we will review the biology and genetic polymorphisms involved in the genesis of gastric precancerous conditions reported to date and discuss the future prospects of this field of study. The associations of gastric precancerous conditions with polymorphisms in the cytotoxin-associated gene A-related genes (e.g. PTPN11 G/A at intron 3, rs2301756), those in the genes involved in host immunity against Helico-bacter pylori (H. pylori) infection (e.g.TLR4 +3725G/C, rs11536889) or polymorphisms of the genes essential for the development/ differentiation of the gastric epithelial cells (e.g. RUNX3 T/A polymorphism at intron 3, rs760805) have been reported to date. Genetic epide-miological studies of the associations between H. pylori-induced gastric precancerous conditions and other gene polymorphisms in these pathways as well as polymor-phisms of the genes involved in other pathways like oxidative DNA damage repair pathways would provide useful evidence for the individualized prevention of these H. pylori-induced gastric precancerous conditions.

Gastric epithelial histology and precancerous conditions

The most common histological type of gastric cancer(GC)is gastric adenocarcinoma arising from the gastric epithelium.Less common variants include mesenchymal,lymphoproliferative and neuroendocrine neoplasms.The Lauren scheme classifies GC into intestinal type,diffuse type and mixed type.The WHO classification includes papillary,tubular,mucinous,poorly cohesive and mixed GC.Chronic atrophic gastritis(CAG)and intestinal metaplasia are recommended as common precancerous conditions.No definite precancerous condition of diffuse/poorly/undifferentiated type is recommended.Chronic superficial inflammation and hyperplasia of foveolar cells may be the focus.Presently,the management of early GC and precancerous conditions mainly relies on endoscopy including diagnosis,treatment and surveillance.Management of precancerous conditions promotes the early detection and treatment of early GC,and even prevent the occurrence of GC.In the review,precancerous conditions including CAG,metaplasia,foveolar hyperplasia and gastric hyperplastic polyps derived from the gastric epithelium have been concluded,based on the overview of gastric epithelial histological organization and its renewal.

A preliminary study on ras protein expression in human esophageal cancer and precancerous lesions

INTRODUCTIONThe esophageal carcinoma is a common malignanttumor in Linzhou City (Linxian) of Henan Provincein northern China.Although the etiology andnatural history of csophageal carcinoma are notclear,a substantial amount of evidence has beenprovided to suggest that the development of humanesophageal squamous cell carcinomas (SCC) is amultistage progressive process.An

Clinical and experimental study of therapeutic effect of Weixibaonizhuan pills on gastric precancerous lesions

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Effect of garlic on micronucleus frequency of peripheral blood lymphocytes in MNNG-induced gastric carcinoma and precancerous lesion in rats

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Effect of garlic and garlic-green tea mixture on serum lipids in MNNG-induced experimental gastriccarcinoma and precancerous lesion

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Expression of bcl-2 oncogene in gastric precancerous lesions and its correlation with syndromes in traditional Chinese medicine

AIM: To observe the protein and mRNA expression of bcl-2 oncogene in gastric precancerous lesions (GPL) and to analyze its correlation with syndromes in traditional Chinese medicine (TCM).METHODS: Sixty-seven patients with GPL confirmed by gastroscopy and pathology were studied, including 39 cases of moderate gastric mucosal dysplasia, 19 casesof severe gastric mucosa dysplasia, g cases of incompletecolon metaplasia. In syndrome differentiation of TCM, 17 cases belonged to the syndrome of qi and yin deficiency of the spleen and stomach complicated by qi stagnation, 21 cases belonged to the syndrome of qi and yin deficiency of the spleen and stomach complicated by stomach heat, 29 cases belonged to the syndrome of qi and yin deficiency of the spleen and stomach complicated by blood stasis. Protein and mRNA expression of bcl-2 oncogene weredetected by labeled streptavidin biotin (LSAB) immunohistochemistry and in situ hybridization respectively. RESULTS: Abnormal expression of protein and mRNA on bcl-2 oncogene was found in GPL, which increased gradually with the course of lesions. In moderate and severe gastric mucosal dysplasia and incomplete colon metaplasia, there was no difference in the expression of bcl-2 oncogene (P＞0.05). In different accompanying syndromes, the expression of protein and mRNA on bcl-2 oncogene increased gradually in the following order: deficiency of both qi and yin of the spleen and stomach accompanying qi stagnation → stomach heat → blood stasis. In GPL, compared with accompanying blood stasis, there was an obvious difference in the expression of bd-2 oncogene between the syndrome of qi and yin deficiency of the spleen and stomach and accompanying stomach heat, so did accompanying qi stagnation (the level of protein: χ2 = 8.45, P＜0.05; the level of mRNA: χ2 = 7.35,P＜0.05).CONCLUSION: Apoptosis-associated bcl-2 oncogene is abnormally expressed in GPL, which correlates with different accompanying syndromes in TCM.

Tumor suppressor gene p16 and Rb expression in gastric cardia precancerouslesions from subjects at a high incidence area in northern China

AIM: To further understand the molecular basis for gastriccardia carcinogenesis and to provide etiological clues.METHODS: Endoscopic mucosa biopsy and histopathologicalexaminations were made on 37 subjects from a high incidencearea for both esophageal and gastric cardia carcinomas innorthem China. All the biopsy samples were fixed in 850 mi. -1 Lalcohol and embedded in paraffin. Each block contained onepiece of tissue and was serially section at 5 μm.Immunohistochemistry (ABC) was carried out on these gastriccardia samples to determine the alterations of p16 and Rb.RESULTS: Based on the histopathlogical examinationtherewere 11 cases of chronic superficial gastritis, 12 cases ofchronic atrophic gastritis and 14 cases of dysplasia. Theimmunostaining demonstrated different levels of unclearimmunostaining of p16 and Rb in normal gastric cardiatissue and the tissues with different severity of lesions. Withthe lesions progressing, the positive immunostaining ratesfor pi6 protein had a decreasing tendency. In contrast, thepositive immunostaining rate for Rb protein had anincreasing tendency. There was a significant negativerelationship between the two parameters. Changes of p16wasCSG 11(100 % ), CAG 7(58 % ), DYS 4(29 % ) andchanges of Rb was CSG 2(18 %), CAG 8(67 %) and DYS 12(86 %), (p＜0.05).CONCLUSION: The alterations of p16 and Rb protein may playa role in the early stages of gastric cardia carcinogenesis.

Effects of San Qi on Gastric Secretion and Protective Factors of Gastric Mucosa in the Rat with Precancerous Lesion of Stomach

In the model rat with precancerous lesion of stomach induced by the combined method of insertion of a spring into the pylorus and high salt hot paste, effects of San Qi (三七 Radix Notoginseng) on gastric secretion and protective factors of stomach were investigated.

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.

Relationship between gastric cancer and precancerous lesions

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ESD与EMR治疗早期结直肠癌、癌前病变的手术效果及并发症观察

目的探究内镜黏膜下剥离术(endoscopic submucosal dissection,ESD)与黏膜切除术(endoscopic mucosal resection,EMR)对早期结直肠癌、癌前病变患者的手术效果及并发症的影响。方法回顾性我院治疗的早期结直肠癌、癌前病变患者120例,根据手术方式分组,对照组55例,观察组65例。对照组行EMR治疗,观察组行ESD手术。对2组患者的手术指标进行比较,观察两组术前及术后7 d的氧化应激水平,术后对患者进行6个月随访,比较其术前及术后的生活质量水平,统计患者术后发生穿孔、感染及出血的情况,并记录患者术后6个月内是否复发。结果与对照组相比,观察组手术时间较长,术中出血量较多,切除的标本厚度及创面直径均大于对照组,差异均有统计学意义(P<0.05)。观察组病灶整块切除率及治愈性切除率与对照组比较,差异无统计学意义(P>0.05)。治疗后,患者的丙二醛(malondialdehyde,MDA)、氧化型谷胱甘肽(glutathione disulfide,GSSG)、皮质醇(cortisol,Cor)水平均有所上升,与术前比较差异有统计学意义(P<0.05),但2组比较差异无统计学意义(P>0.05)。2组术前的生活质量各维度评估结果差异无统计学意义(P>0.05)。经治疗,对患者术后3个月的生活质量再次评估,其生活质量评分均有提高,且观察组患者的升高幅度高于对照组(P<0.05)。观察组穿孔、术中出血、感染的发生率为12.31%,低于对照组(34.55%),术后6个月内,观察组复发1例(1.54%),与对照组复发率(8例14.55%)比较,差异有统计学意义(P<0.05)。结论与EMR相比,对早期结直肠癌、癌前病变患者行ESD治疗,操作难度较大,手术时间较长,但患者术后氧化应激水平变化相当,可以有效降低患者术后复发率,改善术后并发症的发生情况,提高患者生活质量。

声带癌前病变组织中基质金属蛋白酶抑制剂-1、果蝇母亲DDP同源物4表达水平与术后复发和恶变的相关性研究

目的探讨声带癌前病变组织中基质金属蛋白酶抑制剂-1(tissue inhibitor of metalloproteinases 1,TIMP-1)、果蝇母亲DDP同源物4(drosophila mothers against DDP homolog 4,Smad4)表达水平与术后复发和恶变的相关性。方法回顾性分析2018年8月~2021年8月郑州大学第一附属医院收治的162例声带癌前病变患者的临床和病理资料,收集手术切除癌前病变组织(癌前病变组)及病变旁正常黏膜组织(对照组),采用免疫组织化学法检测组织中TIMP-1、Smad4表达情况。分析TIMP-1、Smad4阳性率与临床病理特征的关系,并采用Kaplan-Meier法和Cox回归分析法分析其对术后复发和恶变的影响。结果与对照组正常黏膜组织比较,癌前病变组的TIMP-1阳性率较高,Smad4阳性率较低(P<0.05)。不同病变范围、是否累及前连合、不同程度上皮异常增生患者的TIMP-1、Smad4阳性率存在差异(P<0.05)。术后随访时间24~60个月,中位随访时间36个月,随访期间失访患者6例,随访率96.30%(156/162),随访期间术后复发35例(21.60%),术后恶变16例(9.88%);Kaplan-Meier生存分析显示,TIMP-1阳性患者术后复发率和恶变率高于TIMP-1阴性患者(P<0.05);Smad4阴性患者术后复发率和恶变率高于Smad4阳性患者(P<0.05)。多因素Cox回归分析显示,喉咽反流、病变范围>1/2、中/重度异型增生、TIMP-1阳性、Smad4阴性是复发的独立危险因素(P<0.05),年龄>60岁、累及前连合、TIMP-1阳性、Smad4阴性是恶变的独立危险因素(P<0.05)。结论声带癌前病变组织中TIMP-1高表达、Smad4低表达,且TIMP-1阳性、Smad4阴性表达者术后复发和恶变风险较高。

miR-26a、miR-663联合幽门螺旋杆菌对老年胃癌癌前病变诊断价值

目的探讨分析微小RNA-26a(microRNA-26a,miR-26a)、微小RNA-663(microRNA-663,miR-663)联合幽门螺旋杆菌对老年胃癌癌前病变诊断价值。方法连续入选经胃镜及病理学检查确诊的胃部良性病变、癌前病变或早期胃癌的老年患者136例作为研究对象。采用实时荧光定量聚合酶链反应检测其血清miR-26a、miR-663表达,并采用13 C尿素呼气试验检测幽门螺旋杆菌阳性情况,分析miR-26a、miR-663和幽门螺旋杆菌及联合检测对胃良性病变、癌前病变及早期胃癌等不同病变程度的诊断价值,并绘制(receiver operating characteristic curves,ROC)曲线,评估其诊断准确性。结果胃良性病变、癌前病变、早期胃癌患者性别、年龄、体重指数、吸烟史、饮酒史差异无统计学意义(P>0.05);而胃癌前病变和早期胃癌患者胃癌家族史高于良性病变患者(P<0.05),而癌前病变和早期胃癌患者胃癌家族史差异无统计学意义(P>0.05)。胃癌前病变和早期胃癌患者血清miR-26a、miR-663表达量低于胃良性病变患者,早期胃癌患者血清miR-26a、miR-663表达量低于癌前病变患者,幽门螺旋杆菌阳性率高于胃良性疾病患者(P<0.05),而癌前病变和早期胃癌患者幽门螺旋杆菌阳性率差异无统计学意义(P>0.05)。三者联合检测的敏感度显著高于单一miR-26a检测(χ^(2)=4.680,P=0.031)、单一miR-663检测(χ^(2)=8.223,P=0.004)、单一幽门螺旋杆菌检测(χ^(2)=6.363,P=0.012)。血清miR-26a截断值为2.63时诊断老年胃癌癌前病变的ROC曲线下面积为0.79(95%CI:0.774~0.856),此时的敏感度和特异度分别为75.43%和79.85%;血清miR-663截断值为4.35时诊断老年胃癌癌前病变的ROC曲线下面积为0.83(95%CI:0.796~0.875),此时的敏感度和特异度分别为81.37%和78.56%;幽门螺旋杆菌诊断老年胃癌癌前病变的ROC曲线下面积为0.72(95%CI:0.648~0.769),此时的敏感度和特异度分别为68.93%和78.45%;三者联合诊断老年胃癌癌前病变的ROC曲线下面积为0.89(95%CI:0.815~0.873),此时的敏感度和特异度分别为89.72%和74.43%。结论miR-26a、miR-663联合幽门螺旋杆菌对老年胃癌癌前病变具有较高诊断价值,联合诊断有助于提高诊断敏感度,进而为老年胃癌早期诊断提供指导依据。

加味蜀羊泉散对湿热下注型宫颈鳞状上皮内病变合并高危型人乳头瘤病毒感染术后患者免疫功能及阴道微生态的影响

目的观察加味蜀羊泉散对湿热下注型宫颈鳞状上皮内病变(SIL)合并高危型人乳头瘤病毒(HR-HPV)感染术后患者免疫功能及阴道微生态的影响。方法将112例湿热下注型SIL合并HR-HPV感染宫颈环形电切术(LEEP)患者按照随机数字表法分为2组,对照组56例术后予重组人干扰素α-2b阴道泡腾胶囊治疗,治疗组56例术后在对照组治疗基础上应用加味蜀羊泉散治疗,2组均连续治疗3个月。比较2组术后6个月疗效;比较2组术前、术后6个月中医证候评分、免疫功能、阴道微生态指标变化。结果治疗组中途退出2例,对照组中途退出2例、病例资料缺失2例,最终治疗组54例、对照组52例完成研究。治疗组总有效率92.59%(50/54),对照组总有效率73.08%(38/52),治疗组疗效优于对照组(P<0.05)。2组术后6个月各项中医证候评分及总评分均较本组术前降低(P<0.05);治疗组术后6个月带下量多、色黄或兼绿、质稠或似泡沫、气秽或臭、阴户灼热瘙痒评分及总评分均低于对照组(P<0.05)。2组术后6个月免疫球蛋白(Ig)A、IgM、IgG、CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)均较本组术前升高(P<0.05),CD8^(+)较本组术前降低(P<0.05);治疗组术后6个月IgA、IgM、IgG、CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)均高于对照组(P<0.05),CD8^(+)低于对照组(P<0.05)。2组术后6个月菌群密集度(Ⅱ~Ⅲ级)、菌群多样性(Ⅱ~Ⅲ级)、乳酸菌(Ⅰ~Ⅱa级)均较本组术前升高(P<0.05),pH值较本组术前降低(P<0.05);治疗组术后6个月菌群密集度(Ⅱ~Ⅲ级)、菌群多样性(Ⅱ~Ⅲ级)、乳酸菌(Ⅰ~Ⅱa级)均高于对照组(P<0.05),pH值低于对照组(P<0.05)。结论加味蜀羊泉散治疗湿热下注型SIL合并HR-HPV感染术后患者,能改善患者临床症状,提高HR-HPV转阴率及疗效,可能与改善免疫功能、调节阴道微生态等因素有关。

DNA甲基化预测宫颈癌及癌前病变的研究进展

近年来随着早期筛查的普及,我国的宫颈癌发病率及死亡率均有所下降,细胞学检查及高危型人乳头瘤病毒(human papilloma virus,HPV)检测是目前常用的宫颈癌筛查手段,但二者均有局限性,细胞学检查可能导致疾病漏诊,而高危型HPV检测常导致过度诊疗,因此,探索一种新的宫颈癌筛查或分流手段十分必要。DNA甲基化是一种常见的表观遗传方式,随着DNA甲基化检测技术的发展,其在肿瘤诊疗领域发挥越来越大的作用。近年来发现许多甲基化基因可作为宫颈癌标志物,在宫颈癌筛查及分流方面具有应用前景,并且具有预测疾病转归、采样方便等优势,有利于宫颈癌的早期诊断及治疗。综述DNA甲基化在宫颈癌及宫颈癌前病变中的相关研究进展。

胃癌前状态和癌前病变的管理策略

尽管近年来报道称胃癌发病率有所下降,但其仍是全球第五大癌症死亡原因。晚期胃癌患者常面临着极为有限的治疗方案和较差的预后。而慢性萎缩性胃炎及上皮内瘤变是胃癌发展过程中典型癌前表现。因此,正确认识胃癌前病变和癌前状态的特点和演变规律,从而准确处理胃癌前状态和癌前病变,将极大降低胃癌的发生率,改善患者预后,提高患者生活质量。

谢晶日教授从肝脾论治胃癌前病变经验

谢晶日教授治疗胃癌前病变的经验丰富,认为胃癌前病变以脾胃虚弱为本,气滞、湿阻、血瘀为标,临床症状复杂多变,以本虚标实、虚实夹杂之证多见。临证时,谢晶日教授强调从肝脾论治胃癌前病变的重要性;强调活血解毒,兼化湿浊;重视心理因素在治疗胃癌前病变中的作用,临床多获良效。附验案一则以供参考。

窄带双变焦放大内镜对胃部癌前病变及早期胃癌的诊断价值

目的探究窄带双变焦放大内镜在胃部癌前病变及早期胃癌的诊断价值。方法回顾性分析2019年1月至2020年1月于沧州市人民医院接受胃镜检查出现病灶的300例病人,所有病人入院即行窄带双变焦放大内镜(DF-NBI)检查和靶向活组织检查,2周内择期再行窄带成像放大内镜(ME-NBI)检查和靶向活组织检查。比较两种内镜方法与病理学诊断结果的一致性,分析DF-NBI下胃部癌前病变和早期癌变与MV/MS分型的关系。结果DF-NBI和ME-NBI对于胃部癌前病变和早期胃癌的诊断与病理检查结果的Kappa值分别为0.882和0.857,均具有较好的一致性。DF-NBI的灵敏度为89.4%,阳性预测值为87.1%,阴性预测值为94.1%,准确率为91.8%,略高于ME-NBI(89.0%),特异度为90.7%,略低于ME-NBI(93.1%),但差异无统计学意义(χ^(2)=0.26、0.70,P>0.05)。在DF-NBI下微血管形态与腺管开口形态在诊断早期胃癌上的差异有统计学意义(χ^(2)=209.76、178.81,P<0.05)。结论DF-NBI与ME-NBI对胃部癌前病变和早期胃癌分化程度都具有较高的诊断效能,结合MV/MS分型可提高早期胃癌的检出率,值得临床推广使用。