Loss of heterozygosity on chromosome 17p predicts neoplastic progression in Barrett's esophagus

BACKGROUND AND AIM: Endoscopic surveillance for adenocarcinoma in patients with Barrett's esophagus is costly, with one cancer detected every 48-441 patient years of follow up. Genetic abnormalities, including loss of heterozygosity at sites of tumor suppressor genes, have been detected in malignant and premalignant Barrett's esophagus. The aim of this prospective study was to determine if loss of heterozygosity analysis could identify patients with Barrett's esophagus at greatest risk of adenocarcinoma, for whom endoscopic surveillance is most appropriate. METHODS: Loss of heterozygosity analysis was performed on endoscopic biopsies from 48 patients as part of a Barrett's surveillance program using 14 microsatellite markers shown previously to detect loss of heterozygosity in more than 30% of esophageal adenocarcinomas. Patients were followed up endoscopically for a median of 5 years. RESULTS: Loss of heterozygosity was detected in nine patients. Three patients with loss of heterozygosity on chromosome 5q or 9p did not progress beyond metaplasia. Loss of heterozygosity at 17p11.1-p13 was detected in six patients, all of whom demonstrated dysplasia and/or carcinoma during follow up (four low-grade dysplasia, one high-grade dysplasia and one adenocarcinoma). CONCLUSION: Loss of heterozygosity at 17p11.1-p13 on chromosome 17p identifies patients with Barrett's esophagus at risk of neoplastic progression and can supplement histology in determining the frequency of endoscopy during surveillance.     

Malignant degeneration of Barrett''s esophagus: the role of the Ki-67 proliferation fraction, expression of E-cadherin and p53

Barrett's columnar epithelium with dysplasia is the most important risk factor for adenocarcinoma of the distal esophagus. The molecular mechanisms responsible for progression of columnar metaplasia to dysplasia and invasive carcinoma are mostly unknown. We investigated expression of the tumor suppressor gene p53, E-cadherin expression and cell proliferation in the metaplasia-dysplasia-carcinoma sequence of esophageal adenocarcinoma. In 24 patients with R0-resected adenocarcinomas of the distal esophagus we evaluated the expression of E-cadherin (antibody HECD-1), mutated p53 (antibody DO1) and cell proliferation (antibody MiB1) by immunohistochemistry in sections of adenocarcinoma, columnar metaplasia, with and without dysplasia, and in squamous epithelium of the esophagus. No p53 immunoreactivity was seen in sections of normal squamous epithelium or columnar metaplasia. Fifty per cent of invasive adenocarcinomas stained positive for mutated p53. The p53 expression correlated with the T-category (P = 0.048) and the N-category (P = 0.024). There was a significant decrease in the expression of E-cadherin from columnar metaplasia to dysplasia and to esophageal adenocarcinoma (P < 0.0001). Expression of E-cadherin in columnar metaplasia without dysplasia was similar to that seen in normal squamous epithelium of the esophagus. The Ki-67 proliferation fraction increased significantly from normal squamous epithelium to columnar metaplasia to dysplasia and to invasive carcinoma (P < 0.001), with a marked expansion of the proliferative component. There was no correlation between cell proliferation, E-cadherin expression and the tumor stage. In contrast to the alterations in the p53 expression, a decreased E-cadherin expression and the expansion of the proliferative component represent an early phenomenon in the malignant degeneration of Barrett's esophagus. This might aid in the early detection of esophageal adenocarcinoma.     

反流性食管炎、Barrett食管的食管动力学研究

目的 探讨反流性食管炎(RE)、Barrett食管(BE)的动力学改变。方法 经内镜检查3 400例患者,分 RE、BE、对照组,进行症状调查、食管测压、食管24h pH检测,并行统计学分析。结果 RE与BE组间除吞咽不适外,烧心感、反酸及胸骨后疼痛的症状评分均为RE组大于BE组,且差异有显著性意义。部分RE、BE、对照组间食管运动功能比较,食管下括约肌静息压等差异均无显著性意义。食管24 h pH检测DeMeester评分、pH<4总时间、pH<4时间的百分比等 RE、BE组高于对照组,差异有显著性意义,但RE、BE组间差别无显著性意义。结论 食管反流症状与食管黏膜的内镜下表现不一致;食管组织化生与食管运动功能间无相关。     

"Z"型及网状食管支架置入后的病理学比较研究

目的探讨Z型及网状支架置入实验犬食管后局部的形态学变化特点.方法选择成年健康实验犬,均分为Z型组和网状组,采取自体阔筋膜移植固定法置入Z型或网状食管支架,分别于术后1,2,4,8 wk分批处死每组动物,取出置架部位的食管组织,进行大体、光镜、电镜分析,并比较两组的差异.结果自体阔筋膜移植固定法能有效地固定食管支架.支架术后1,2 wk局部食管粘膜炎症反应显著,成纤维细胞处于旺盛的增殖及分泌状态,有广泛肉芽组织形成及部分纤维化,食管组织开始向管腔内生长;术后4,8 wk增生组织已完全覆盖支架结构,并连接成片,管腔明显狭窄,局部大量的纤维结缔组织形成,炎症反应缓解.两组实验标本病理形态基本相似,仅"网状"组于术后1,2 wk炎症反应明显,粘膜广泛出现溃疡.结论支架术后食管组织主要表现为肉芽组织形成及纤维化,术后4,8 wk随着炎性反应的减弱,纤维化过程渐趋稳定.网状及Z型支架术后的病理过程基本一致,网状支架术后局部炎性反应显著加重.     

内镜食道静脉瘤套扎器治疗直肠神经内分泌肿瘤的疗效分析

目的评估超声内镜结合内镜食道静脉瘤套扎器行内镜下圈套器法黏膜切除术(EMR-L)治疗直肠神经内分泌肿瘤(NENs)的临床有效性、安全性以及技术的可行性。方法回顾性分析北京世纪坛医院消化内科2015年11月-2017年11月收治的13例直肠NENs患者临床资料,治疗前均行超声内镜检查,后进行EMR-L切除病变。观察患者内镜表现、EMR-L操作过程及其并发症、病理结果,术后定期结肠镜随访。结果 13例患者顺利完成EMR-L切除病变,耗时10 min 36 s~52 min 21 s,平均(21.9±10.6)min。1例患者发生急性出血,予药物喷洒及钛夹封闭创面治疗后出血停止。无急性或迟发性直肠出血、穿孔等并发症。结论应用内镜食道静脉瘤套扎器行EMR-L可有效、安全的切除小于1.0 cm的直肠NENs,同时治疗费用较食管静脉曲张连环套扎器少,有很好的临床应用价值。     

Acute esophageal necrosis after kidney transplantation: A case report

Rationale:Acute esophageal necrosis (AEN) is a rare syndrome with characteristic endoscopic and pathologic findings. It usually results from a combination of tissue hypoperfusion, impaired local defense barriers, and massive reflux of gastric contents. We report a case of AEN after a kidney transplant.Patient concerns:A 53-year-old man with hypertension and end-stage renal disease presented with abdominal pain and a single episode of hematemesis 14 days after kidney transplantation.Diagnosis:Upper endoscopy revealed circumferential black coloration in the mid to lower esophageal mucosa. Esophageal biopsy showed ulcer, and immunostains were negative for viral etiology.Interventions:Conservative management was done with total parenteral nutrition and proton pump inhibitor.Outcomes:The patient experienced no further episodes of hematemesis or abdominal pain and follow-up endoscopy showed remarkable changes from the black mucosa to a red friable mucosa with whitish exudates.Lessons:In the case, AEN occurred in the setting of normal blood pressure after major surgery despite the absence of preceding factors such as hypotension and infections. The possibility of AEN should be considered in patients with solid organ transplantation who present with abdominal pain, dysphagia, and hematemesis.     

过表达LATS1降低食管癌Eca109细胞增殖

目的运用慢病毒转染技术在食管癌Eca109细胞中过表达LATS1基因,探究LATS1调控Eca109细胞增殖、凋亡及周期的作用及机制.方法构建LA TS1基因的慢病毒载体转染Eca109细胞系,RT-PCR检测细胞中LATS1mRNA的表达;Western blot检测LATS1、YAP、BAX/BCL-2的蛋白表达水平;MTS检测细胞增殖;流式细胞术检测细胞凋亡及周期;hochest33258观察细胞凋亡染色.结果 LATS1慢病毒载体转染Eca109细胞后,目的基因组(Ad-LATS1)LATS1 mRNA及LATS1蛋白表达、BAX蛋白表达明显高于对照组(CON)及阴性对照组(Ad-GFP),而YAP、BCL-2的蛋白表达明显低于对照组及Ad-GFP组(P＜0.05);Ad-LATS1组Eca109细胞的增殖率从第5天开始明显低于对照组及Ad-GFP组(P＜0.05);Ad-LATS1组细胞较Ad-GFP及对照组G1期比例明显增高而S期比例明显缩短,凋亡率明显增高(P＜0.05),细胞荧光染色强度及范围也增高.结论 LATS1基因可上调BAX、下调YAP、BCL-2使Eca109凋亡,并诱导G1期延长、S期缩短来降低其增殖力.     

How to Make a Barrett Esophagus: Pathophysiology of Columnar Metaplasia of the Esophagus

Barrett esophagus is defined as a specialized intestinal replacing the squamous epithelium of the esophageal mucosa in response to gastroesophageal reflux. Barrett metaplasia is a healing process that develops to protect the esophagus from further damage. Although mechanisms by which Barrett metaplasia evolves toward dysplasia and adenocarcinoma have been extensively studied, the process by which squamous epithelium is replaced by specialized intestinal metaplasia is poorly understood. Barrett esophagus develops when defense mechanisms in the esophageal mucosa (luminal secretion of mucus, bicarbonate, growth factors, etc.) are overwhelmed by an ongoing cycle of mucosal injury and repair. Hydrogen ion, pepsin, trypsin, and bile acids are considered harmful agents that synergistically invade the esophageal mucosa. Areas of destroyed squamous epithelium are then progressively reepithelized by a columnar epithelium that may originate from multipotent stem cells located within the basal layer of the normal esophageal mucosa or in the ducts of submucosal glands.     

TP53 mutations in malignant and premalignant Barrett''s esophagus

In order to improve the efficacy of endoscopic surveillance of Barrett's esophagus, markers of neoplastic progression in addition to dysplasia are required. The aim of the present study was to assess TP53 mutational analysis as a method of identifying patients with Barrett's esophagus who are at greatest risk of adenocarcinoma, for whom endoscopic surveillance is most appropriate. TP53 mutational analysis was initially performed on premalignant and malignant tissue from 30 patients undergoing esophagectomy for adenocarcinoma, and on premalignant biopsies from 48 patients participating in a Barrett's surveillance program. Surveillance patients were followed up endoscopically and histologically for a median of 5 years following TP53 assessment. Mutational analysis was performed by single-strand conformation polymorphism analysis and direct DNA sequencing. TP53 mutations were detected in 10 of 30 esophageal adenocarcinomas, and were more common in well-differentiated carcinomas. An identical TP53 mutation was detected in carcinoma and adjacent dysplasia. Two patients with premalignant Barrett's esophagus had TP53 mutations and one of these patients developed adenocarcinoma on follow up whilst the other has not yet progressed beyond metaplasia. No patient without TP53 mutation developed high-grade dysplasia or adenocarcinoma. TP53 mutations are detected in 33% of esophageal adenocarcinomas and in 4% of premalignant Barrett's esophagus in patients undergoing endoscopic surveillance. TP53 mutation can be detected before the development of high-grade dysplasia or carcinoma, and may be useful in stratifying the risk of adenocarcinoma in patients with Barrett's esophagus.     

Reflux injury of esophageal mucosa: experimental studies in animal models of esophagitis, Barrett''s esophagus and esophageal adenocarcinoma

Barrett's esophagus (BE), a gastroesophageal reflux associated complication, is defined as the replacement of normal esophageal squamous mucosa by specialized intestinal columnar mucosa with the appearance of goblet cells. The presence of BE is associated with an increased risk of developing esophageal adenocarcinoma (EAC). Although the exposure of gastroduodenal contents to the esophageal mucosa is considered to be an important risk factor for the development of esophagitis, BE and EAC, the mechanisms of reflux esophageal injury are not fully understood. Animal models are now being used extensively to identify the mechanisms of damage and to devise protective and mitigating strategies. Experimental studies on animal models by mimicking the processing of gastroesophageal reflux injury have bloomed during the past decades, however, there is controversy regarding which experimental model for reflux esophagitis, experimental BE and experimental EAC is best. In this review article we aim to clarify the basic understanding of gastroesophageal reflux injury and its complications of BE and EAC, as well as to present current understanding of the reflux experimental models. The animal models of experimental esophageal injury are summarized with focus on the surgical procedures to guide the investigator in choosing or developing a correct animal model in future studies. In addition, our own experimental studies of the animal models are also briefly discussed.