Confusion and prospects for carcinogenesis of gastric adenoma and dysplasia: What is the correct answer currently?

There are differences in the diagnoses of superficial gastric lesions between Japan and other countries.In Japan,superficial gastric lesions are classified as adenoma or cancer.Conversely,outside Japan,the same lesion is classified as low-grade dysplasia(LGD),high-grade dysplasia,or invasive neoplasia.Gastric carcinogenesis occurs mostly de novo,and the adenoma-carcinoma sequence does not appear to be the main pathway of carcinogenesis.Superficial gastric tumors can be roughly divided into the APC mutation type and the TP53 mutation type,which are mutually exclusive.APC-type tumors have low malignancy and develop into LGD,whereas TP53-type tumors have high malignancy and are considered cancerous even if small.For lesions diagnosed as category 3 or 4 in the Vienna classification,it is desirable to perform complete en bloc resection by endoscopic submucosal dissection followed by staging.If there is lymphovascular or submucosal invasion after mucosal resection,additional surgical treatment of gastrectomy with lymph node dissection is required.In such cases,functionpreserving curative gastrectomy guided by sentinel lymph node biopsy may be a good alternative.

Chromoendoscopy of gastric adenoma using an acetic acid indigocarmine mixture

AIM:To investigate the usefulness of chromoendoscopy,using an acetic acid indigocarmine mixture(AIM),for gastric adenoma diagnosed by forceps biopsy.METHODS:A total of 54 lesions in 45 patients diagnosed as gastric adenoma by forceps biopsy were prospectively enrolled in this study and treated by endoscopic submucosal dissection(ESD)between January 2011 and January 2012.AIM-chromoendoscopy(AIMCE)was performed followed by ESD.AIM solution was sprinkled and images were recorded every 30 s for 3min.Clinical characteristics such as tumor size(<2cm,≥2 cm),surface color in white light endoscopy(WLE)(whitish,normochromic or reddish),macroscopic appearance(flat or elevated,depressed),and reddish change in AIM-CE were selected as valuables.RESULTS:En bloc resection was achieved in all 54 cases,with curative resection of fifty two lesions(96.3%).Twenty three lesions(42.6%)were diagnosed as welldifferentiated adenocarcinoma and the remaining 31lesions(57.4%)were gastric adenoma.All adenocarcinoma lesions were well-differentiated tubular adenocarcinomas and were restricted within the mucosal layer.The sensitivity of reddish color change in AIM-CE is significantly higher than that in WLE(vs tumor size≥2 cm,P=0.016,vs normochromic or reddish surface color,P=0.046,vs depressed macroscopic type,P=0.0030).On the other hand,no significant differences were found in the specificity and accuracy.In univariate analysis,normochromic or reddish surface color in WLE(OR=3.7,95%CI:1.2-12,P=0.022)and reddish change in AIM-CE(OR=14,95%CI:3.8-70,P<0.001)were significantly related to diagnosis of early gastric cancer(EGC).In multivariate analysis,only reddish change in AIM-CE(OR=11,95%CI:2.3-66,P=0.0022)was a significant factor associated with diagnosis of EGC.CONCLUSION:AIM-CE may have potential for screening EGC in patients initially diagnosed as gastric adenoma by forceps biopsy.

Endoscopic submucosal dissection of gastric adenomas using the clutch cutter

AIM To evaluate the efficacy and safety of endoscopic submucosal dissection(ESD) using the clutch cutter(CC)(ESD-CC) for gastric adenoma(GA).METHODS From June 2007 to August 2015,122 consecutive patients with histological diagnoses of GA from specimens resected by ESD-CC were enrolled in this prospective study.The CC was used for all ESD steps(marking,mucosal incision,submucosal dissection,and hemostatic treatment),and itstherapeutic efficacy and safety were assessed.RESULTS Both the en-bloc resection rate and the R0 resection rate were 100%(122/122).The mean surgical time was 77.4 min,but the time varied significantly according to tumor size and location.No patients suffered perforation.Post-ESD-CC bleeding occurred in six cases(4.9%) that were successfully resolved by endoscopic hemostatic treatment.CONCLUSION ESD-CC is a technically efficient,safe,and easy method for resecting GA.

Clinical features of gastric adenoma detected within 3 years after negative screening endoscopy in Korea

Background:Early detection and management of gastric adenoma are important for preventing gastric cancer.The present study aimed to evaluate the predictors of missed gastric adenoma on screening endoscopy in Korea and identify the risk factors associated with interval precancerous gastric lesions.Methods:All cases of gastric adenomas diagnosed via screening endoscopy between 2007 and 2019 were reviewed.Among them,those who had undergone endoscopy within 3 years were included in the present study.Missed gastric adenoma was defined as gastric adenoma diagnosed within 3 years after negative screening endoscopy.Results:In total,295 cases of gastric adenoma were identified.Of these,95(32.2%)were missed gastric adenoma cases(mean age,60.6 years;average interval between final and index endoscopies,12.6months);the remaining 200(67.8%)were newly detected adenoma cases.Univariate analysis revealed thatmale sex,endoscopist experience,observation time,and presence of gastric intestinalmetaplasia(pathologically proven)were associated with missed gastric adenoma.Multivariate analysis revealed that gastric intestinal metaplasia(odds ratio[OR],2.736;95%confidence interval[CI],1.320–5.667;P=0.007)and shorter observation time of the index screening endoscopy(B,0.011;OR,0.990;95%CI,0.986–0.993;P<0.001)were independent risk factors for missed gastric adenoma.The optimal cut-off for the observation time for detecting gastric adenoma was 3.53minutes(area under curve,0.738;95%CI,0.677–0.799;P<0.001).Conclusions:Gastric intestinal metaplasia is an indication of missed gastric adenoma.Therefore,careful inspection of gastric mucosa with gastric intestinal metaplasia and proper observation time can lower the possibility of missing the gastric adenoma during screening.

Oxyntic gland adenoma endoscopically mimicking a gastric neuroendocrine tumor: A case report

Gastric adenocarcinoma is one of the most common malignancies worldwide.Histochemical and immunohistologic analyses classify the phenotypes of gastric adenocarcinoma into several groups based on the variable clinical and pathologic features.A new and rare variant of gastric adenocarcinoma with chief cell differentiation(GA-CCD)has recently been recognized.Studies reporting the distinct clinicopathologic characteristics proposed the term oxyntic gland polyp/adenoma because of the benign nature of the GACCD.Typically,GA-CCD is a solitary mucosal lesion that develops either in the gastric cardia or fundus.Histologically,this lesion is characterized by tightly clustered glands and anastomosing cords of chief cells.Immunohistochemically,GA-CCD is diffusely positive for mucin(MUC)6 and negative for MUC2and MUC5AC.However,other gastric tumors such as a gastric neuroendocrine tumor or fundic gland polyp have been difficult to exclude.Because GA-CCD tends to be endoscopically misdiagnosed as a neuroendocrine tumor or fundic gland polyp,comprehensive assessment and observation by an endoscopist are strongly recommended.Herein,we report a rare case of oxyntic gland adenoma endoscopically mimicking a gastric neuroendocrine tumor that was successfully removed by endoscopic mucosal resection.

胃泌酸腺肿瘤49例临床病理学分析

目的:分析胃泌酸腺肿瘤的临床病理学特征。方法:选取2016年1月—2020年12月于山东大学第二医院确诊的49例胃泌酸腺肿瘤包括泌酸腺腺瘤(OGA)和胃底腺型腺癌(GA-FG)为研究对象,回顾性分析其临床资料、内镜表现、组织学特征、免疫表型并进行随访。结果:胃泌酸腺肿瘤的患者年龄19~83岁,平均(57.3±2.4)岁,男女比例为24∶25。病变主要位于胃体(27/49)和胃底(15/49)。内镜下有4种表现:扁平隆起型、息肉样、扁平型和凹陷型。部分病变可见扩张的树枝状血管。48例为单发,病变最大径平均为(3.9±0.5)mm(1.0~7.0 mm)。7例表现为黏膜下浸润,浸润深度均小于500μm。该肿瘤由密集的腺体吻合呈条索状,镜下呈不规则分支状、迷路状。该类肿瘤细胞分化好,形态类似于泌酸腺细胞,以主细胞为主,细胞核轻度增大,有轻微异型性,核分裂像少见。免疫标志物MUC6(100%)和Pepsinogen-Ⅰ(83%)呈弥漫性阳性,H+/K+-ATPase不同程度阳性(58%)。结论:泌酸腺肿瘤是一种新的胃肿瘤组织学类型,具有独特的临床病理特征,该类肿瘤发病率较低,预后良好,但仍需长期随访。

Probe-based confocal endomicroscopy is accurate for differentiating gastric lesions in patients in a Western center

Objective： Probe-based confoeal laser endomicroscopy （pCLE） technique may improve the diagnosis of gastric mucosal lesions allowing acquisition of high-resolution in vivo images at the cellular and mierovaseular levels. This study aims to evaluate the accuracy of pCLE for the differential diagnosis of non-neoplastic and neoplastic gastric lesions.Methods： Twenty gastric mucosal lesions from 10 patients were evaluated during endoscopic procedure and were examined by pCLE. Diagnostic pCLE was followed by biopsies or endoscopic resection of suspected lesions. A senior pathologist evaluated the specimens and was blinded to the pCLE results.Results： Patients＇ mean age was 68.3 （range, 42-83） years and six were men. Thirteen suspicious flat or elevated lesions （classified as 0-Is, 0-IIa or 0-IIa ＋ IIc） and seven pre-malignant lesions （atrophy and intestinal metaplasia） were evaluated. One patient was studied during his long-term follow-up after partial gastrectomy and presented severe atrophy, intestinal metaplasia, and xanthomas at the stump mucosa. The location of gastric lesions was in the body （n=10 lesions）, the antrum （n=9） and the incisura angularis （n=1）. All neoplastic lesions and all but one benign lesion were properly diagnosed by pCLE. pCLE incorrectly diagnosed one small antrum lesion as adenoma, however the final diagnosis was intestinal metaplasia. The final histological diagnosis was neoplastic in 9 and benign lesions in 11. In this small case series, pCLE accuracy was 95% （19/20 lesions）.Conclusions： pCLE is accurate for real time histology of gastric lesions, pCLE may change the management of patients with gastric mucosal lesions, guiding biopsies and endoscopic resection, and avoiding further diagnostic workup or unnecessary therapy.

Gastric Polyps in a Digestive Endoscopy Center in Dakar

Introduction: The gastric polyp is a tumor protruding into the gastric lumen. It is asymptomatic most often with a risk of malignant degeneration closely related to its histological nature. These data are very rare in Africa. Objectives: Reporting the frequency and endoscopic and histological characteristics of gastric polyps in the digestive endoscopy center of Aristide Le Dantec hospital in Dakar. Patients and methods: This was a retrospective study carried out in the digestive endoscopy center of Aristide Le Dantec Hospital in Dakar from January 2012 to December 2016. We have included all patients with one or more gastric polyps coupled with histological findings available. Results: There were 60 patients with gastric polyps, hence a prevalence of 0.8%. We included 37 patients. Their mean age was 46 years [21 years - 75 years]. The sex-ratio was 0.48. Epigastralgia was the most frequent endoscopic indication (51.3%). The polyp was unique in 26 patients (70.3%) with an average size of 6.87 mm [2 - 15 mm]. Polyps were sessile in 31 cases (83.8%) and pediculate in 6 cases (16.2%). They were most often in the antrum (51.4%). Antral erosions (13.5%) and fundic atrophy (13.5%) were the main associated endoscopic lesions. These were hyperplastic polyps in 27% of cases and adenoma in 16.2% of cases. Chronic atrophic gastritis (10.8%) and intestinal metaplasia (10.8%) were the main histological lesions associated with polyps. Helicobacter pylori (Hp) were present in 17 patients (45.9%). Conclusion: The prevalence of gastric polyps is 0.8% in the endoscopy center of Aristide Le Dantec hospital. They are usually hyperplastic or adenomatous.

Gastric dysplasia may be an independent risk factor of an advanced colorectal neoplasm

AIM: To evaluate the relationship between gastric dysplasia and Helicobacter pylori (H pylori) and the occurrence of colorectal adenoma, and to defi ne the necessity for colonoscopy in patients with gastric dysplasia or H pylori infection.METHODS: From May 2005 to February 2008, 133 patients with established gastric dysplasia by gastroduo-denoscopy (EGD) were additionally investigated by colonoscopy. The authors compared results with those of 213 subjects who underwent both EGD and colonoscopy during the same period at the author’s Health Promotion Center as a control group. H pylori infection was evaluated in both the gastric dysplasia and control groups.RESULTS: The mean age of all 346 study subjects was 54.1 ± 10.5 years, and there were 258 (73%) men and 87 (27%) women. No signif icant difference was found between the H pylori positive and negative subjects in terms of the prevalence of colorectal adenoma and advanced colorectal adenoma (P = 0.261). Patients with gastric dysplasia showed no elevated risk of colorectal adenoma (OR = 0.910, 95% CI: 0.587-1.411, P = 0.738), but had a signif icantly higher risk of having advanced colorectal adenoma (OR = 3.382, 95% CI: 1.700-6.342, P = 0.000).CONCLUSION: The study emphasizes the need for colon surveillance in patients with gastric dysplasia, regardless of H pylori infection.

Endoscopic excision of a prolapsing malignant polyp which caused intermittent gastric outlet obstruction

A 69-year-old male with chronic lymphocytic leukemia presented with iron deficiency anemia and post-prandial abdominal fullness. Endoscopy showed a large polyp on a stalk, protruding through the pylorus into the duodenum causing intermittent gastric outlet obstruction. While prolapsing gastric antral polyps are usually benign and hyperplastic, inflammatory or regenerative in type, excisional snare polypectomy here led to complete resolution of his symptoms, but showed a malignant polyp.

Treatment strategy for gastric non-invasive intraepithelial neoplasia diagnosed by endoscopic biopsy

Treatment strategies,whether as follow-up or"total incisional biopsy"for gastric noninvasive intraepithelial neoplasia diagnosed by examination of an endoscopic forceps biopsy specimen,are controversial due to problems associated with the diagnostic accuracy of endoscopic forceps biopsy and questions about the safety and efficacy of endoscopic treatment.Based on the histological findings of the biopsy specimen,it is difficult to differentiate between reactive or regenerative changes,inflammation and neoplastic changes,intraepithelial and invasive tumors.Therefore,gastric neoplasia diagnosed as noninvasive intraepithelial often develop into invasive carcinoma during follow-up.Recent advances in endoscopic modalities and treatment devices,such as image-enhanced endoscopy and highfrequency generators,may make endoscopic treatment,such as endoscopic submucosal dissection(ESD),a therapeutic option for gastric intraepithelial neoplasia,including low-grade neoplasms.Future studies are required to evaluate whether ESD is a valid strategy for gastric intraepithelial neoplasm with regard to safety and cost effectiveness.

Epigenetic alterations in gastric carcinogenesis

Gastric cancer is believed to result in part from the accumulation of multiple genetic alterations leading to oncogeneoverexpression and tumor suppressor loss. Epigenetic alterations as a distinct and crucial mechanism to silence a varietyof methylated tissue-specific and imprinted genes, have been extensively studied in gastric carcinoma and play impor-tant roles in gastric carcinogenesis. This review will briefly discuss the basic aspects of DNA methylation and CpGisland methylation, in particular the epigenetic alterations of certain critical genes implicated in gastric carcinogenesisand its relevance of clinical implications.

Inverted cystic tubulovillous adenoma involving Brunner’s glands of duodenum

Benign neoplasia of the duodenum are very rare. Moreover, duodenal tubulovillous adenomas are more uncommon lesions. The microscopic structure of tubulovillous adenoma has frond-like projection of mucosa with branching papillary structure and generally upward growth into the lumen. We describe a 72-year-old man who showed aduodenal tubulovillous adenoma with unusual inverted cystic growth pattern. Interestingly, this tubulovillous adenomatous lesion was interrupted by gastric metaplasia in the deep portion of the cyst and was closely surrounded by Brunner’s glands. Although histogenesis of gastric metaplasia of duodenum is not fully understood, Brunner’s glands has been suggested as a precursor for gastric metaplasia. Therefore, these findings argued that this adenoma arises from Brunner’s glands through gastric metaplasia. This is the first case of inverted cystic tubulovillous adenoma involving Brunner’s glands of duodenum with gastric metaplasia.

High expression of APC is an unfavorable prognostic biomarker in T4 gastric cancer patients

BACKGROUND Adenoma polyposis coli(APC)mutation is associated with tumorigenesis via the Wnt signaling pathway.AIM To investigate the clinical features and mechanism of APC expression in gastric cancer(GC).METHODS Based on APC expression profile,the related genome-wide mRNA expression,microRNA(miRNA)expression,and methylation profile in GC,the relationship between APC and GC,as well as the prognostic significance of APC were systematically analyzed by multi-dimensional methods.RESULTS We found that high expression of APC(APC^high)was significantly associated with adverse outcomes of T4 GC patients.Genome-wide gene expression analysis revealed that varying APC expression levels in GC were associated with some important oncogenes,and corresponding cellular functional pathways.Genomewide miRNA expression analysis indicated that most of miRNAs associated with high APC expression were downregulated.The mRNA-miRNA regulatory network analysis revealed that down-regulated miRNAs affected their inhibitory effect on tumor genes.Genome-wide methylation profiles associated with APC expression showed that there was differential methylation between the APC^high and APC^low groups.The number of hypermethylation sites was larger than that of hypomethylation sites,and most of hypermethylation sites were enriched in CpG islands.CONCLUSION Our research demonstrated that high APC expression is an unfavorable prognostic factor for T4 GC patients and may be used as a novel biomarker for pathogenesis research,diagnosis,and treatment of GC.

结肠息肉与幽门螺杆菌感染及胃息肉的关系

目的研究结肠息肉与幽门螺杆菌(Hp)感染及胃息肉的关系。方法选取2014年10月-2019年8月该院接受胃镜和结肠镜检查的患者235例。依据结肠镜结果,将患者分为结肠息肉组(119例)和对照组(116例)。统计分析各组Hp感染率。结果左半结肠息肉组的Hp感染率高于对照组,腺瘤性息肉组和增生性息肉组的Hp感染率高于对照组,差异均有统计学意义(P<0.05)。各亚组组内Hp感染率比较,差异无统计学意义(P>0.05)。两组患者胃息肉发生率比较,差异无统计学意义(P>0.05)。结论Hp感染可促进结肠息肉的发生和发展。结肠腺瘤性息肉和增生性息肉与Hp感染相关。对于感染Hp的结肠腺瘤性息肉和增生性息肉患者,建议立即进行息肉切除术。结肠息肉的存在与胃息肉的存在没有直接关系。

胃泌酸腺腺瘤和胃底腺型腺癌临床病理特征分析

目的 探讨胃泌酸腺腺瘤(gastric oxyntic gland adenoma,GOGA)和胃底腺型腺癌(gastric adenocarcinoma of fundic gland type,GA-FC)的临床、病理特征、诊断及预后。方法 收集2020年1月—2021年12月4例GOGA和2例GA-FC,分析临床、病理、免疫组化特征及预后,并复习相关文献。结果 4例GOGA内镜示肿物与周边黏膜边界不清的褪色样隆起或平坦的黏膜下病变,病理表现为腺体融合呈管状、筛状,边缘规则无成角,Ki67 <2%;2例GA-FC内镜示肿物与周边黏膜边界清楚的褪色样隆起或平坦的黏膜下病变,表面可有不规则的结构,病理结构异型更明显,腺体融合呈筛状、迷路样,边缘不规则可见成角,间质轻度纤维化,Ki67> 2%。结论 泌酸腺腺瘤与胃底腺型腺癌两者属于同一生物学谱系的两端,两者在临床病理上具有共性的同时也有各自的特性。

胃底腺型胃癌诊断与治疗进展

胃底腺型胃癌(GA-FG)于2007年首次报道,其中描述了胃底腺癌的主细胞分化现象。其表现为分化型胃癌,来源于非萎缩正常胃底腺深部,属于胃癌的一种新的组织学类型。但这种病变的性质还存在争议,病理学界也缺乏对GA-FG的认识,其形态学和生物学行为与常见胃癌不同,易于漏诊或误诊。GA-FG的发病率较低,病因尚不明确,临床表现无特异性,但总体是一种分化良好的肿瘤,大多数GA-FG仅局限于黏膜或黏膜下层,其侵袭性低于传统的肠型或弥漫性胃癌,并遵循良性病程。文章从流行病学、肿瘤学表现及治疗预后等方面,对有关GA-FG目前现有文献进行探讨和总结,并对其诊治进行分析与展望,为改善该类患者预后提供理论基础。

TFF3在胃癌、癌前病变及胃腺瘤中的表达及其与血管生成的关系

目的:分析三叶因子3(TFF3)在不同胃黏膜病变中的表达及其与间质微血管密度(MVD)值的关系,探讨其在胃癌、癌前病变及胃腺瘤发生、发展中的作用.方法:应用免疫组织化学PV6000法检测20例正常胃黏膜、20例胃腺瘤、20例萎缩性胃炎伴肠化生、20例不典型增生、40例胃癌组织中TFF3的表达,同时检测MVD值,以抗CD34标记.结果:TFF3在胃腺瘤、萎缩性胃炎伴肠化生、不典型增生和胃癌各组表达均高于正常组(50.0%,65.0%,70.0%,57.5% vs 5.0%,均P<0.01).胃癌MVD值高于正常胃黏膜、胃腺瘤、萎缩性胃炎伴肠化生和不典型增生(30.65±6.04 vs 14.87±3.06,22.33±3.78,23.16±3.20,25.22±4.66,均P<0.01),各组MVD值均高于正常胃黏膜组(均P<0.01).TFF3表达和MVD值与胃癌淋巴结转移和分期有关(均P<0.05),MVD值还与胃癌浸润深度有关(P<0.05).TFF3阳性表达组的MVD值明显高于TFF3阴性组(34.53±4.45 vs 25.39±3.25,P<0.01).结论:TFF3可能是胃黏膜癌变过程中的早期分子事件,在胃黏膜癌变和癌变后的恶性演进过程中起作用,对胃癌早期诊断和预测胃癌发生转移可能具有重要的提示作用.

HIF-1α基因转染人胃腺癌SGC7901细胞对裸鼠移植瘤的影响及机制

目的探讨低氧诱导因子(HIF)-1α基因转染人胃腺癌SGC7901对裸鼠移植瘤血管生成及Eph A2表达的影响及其可能机制。方法采用HIF-1α基因重组质粒p GCsish HIF-1α,转染胃腺癌SGC7901细胞并接种裸鼠(SGC7901/shRNA,实验组),建立裸鼠皮下人胃腺癌移植瘤模型,动态观测裸鼠肿瘤体积和质量;设SGC7901(未转染组)、转染空质粒的SGC7901(SGC7901/Neo,空载体组)为对照。观察移植瘤生长情况,8周后,获取移植瘤模型瘤组织,称取湿重,免疫组化SP法检测移植瘤组织的微血管密度,Western blot检测上皮细胞激酶A2(Eph A2)表达。结果与未转染组比较,空载体组瘤体积、质量改变不明显,HIF-1α转染的实验组的瘤体积、质量明显降低;HIF-1α转染的实验组诱导血管增生、形成血管生成拟态和Eph A2蛋白表达较未转染组组、空载体组明显降低(P<0.05,P<0.01)。结论 HIF-1α基因转染可明显抑制裸鼠人胃腺癌移植瘤的生长,该作用可能与其抑制肿瘤血管新生、形成血管拟态及Eph A2蛋白表达有关。

β-连环蛋白和APC蛋白在胃腺瘤和胃癌中的表达及意义

目的观察β-连环蛋白和家族性腺瘤样息肉病蛋白(adenomatous polyposis coli protein,APC蛋白)在正常胃黏膜、胃腺瘤和胃癌组织中的表达,探讨其在胃癌发生、发展中的作用。方法经胃镜活检病理检查证实的126例不同胃组织标本,包括40例正常胃黏膜、38例胃腺瘤性息肉(胃腺瘤)和48例胃腺癌组织,以免疫组化ABC法检测标本中中β-连环蛋白和APC蛋白的表达。结果正常胃黏膜、胃腺瘤、胃癌组织β-连环蛋白和APC蛋白异常表达率呈递增趋势,经两两比较,差异均有统计学意义(P<0.05)。胃癌组织中β-连环蛋白和APC蛋白具有显著相关性(r=1.0,P<0.05),胃腺瘤中两者无明显相关性(r=0.169,P=0.430)。结论β-连环蛋白和APC蛋白在胃癌的发生、发展中起重要作用,但两者在胃腺瘤中的相互作用及具体机制有待进一步研究。