内镜下结晶紫染色结合病理活检对提高Barrett食管诊断准确率及其肠化型检出率的研究

目的通过内镜下结晶紫染色结合病理活检提高对Barrett食管(BE)的诊断准确率及肠化型BE检出率。方法选择我院近两年166例经内镜检查疑诊为BE病变的患者为研究对象,随机分为常规内镜组和色素内镜组。常规内镜组采取内镜检查结合病理活检的方法。色素内镜组先用0.05%结晶紫染色液进行染色,根据染后黏膜变化选择病理活检部位,比较两组的准确率和肠化型BE的检出率。结果色素内镜组BE的诊断准确率为86.42%,肠化型BE的检出率为27.16%;常规内镜组分别为64.70%和10.59%,两组比较有显著差异性。结论内镜下结晶紫染色结合病理活检诊断BE的方法和传统的普通内镜结合病理活检比较,其诊断准确率和肠化型BE的检出率明显提高,是一种简单、实用的检查方法,值得推广。     

Z-line alterations and gastroesophageal reflux: an endoscopic population-based prospective cohort study

Abstract

Background and study aims: Barrett's esophagus is a premalignant condition in the distal esophagus associated with esophageal adenocarcinoma. Since gastroesophageal reflux is known to be of etiological importance in both Barrett's esophagus and esophageal adenocarcinoma, we aimed to study which endoscopic alterations at the Z-line can be attributed to a previous history of reflux symptoms.

Patients and methods: From 1988, a population cohort in Sweden has been prospectively studied regarding gastrointestinal symptoms, using a validated questionnaire. In 2012, the population was invited to undergo a gastroscopy and participate in the present study. In order to determine which endoscopic alterations that can be attributed to a previous history of gastroesophageal reflux, three different endoscopic definitions of columnar-lined esophagus (CLE) were used: (1) ZAP I, An irregular Z-line with a suspicion of tongue-like protrusions; (2) ZAP II/III, Distinct, obvious tongues of metaplastic columnar epithelium; (3) CLE ≥1?cm, The Prague C/M-classification with a minimum length of 1?cm.

Results: A total of 165 community subjects were included in the study. Of these, 40 had CLE?≥?1?cm, 99 had ZAP I, and 26 had ZAP II/III. ZAP II/III was associated with an over threefold risk of previous GER symptoms (OR: 3.60, CI: 1.49–8.70). No association was found between gastroesophageal reflux and ZAP I (OR: 2.06, CI: 0.85–5.00), or CLE ≥1?cm (OR: 1.64, CI: 0.77–3.49).

Conclusions: In a general community, the only endoscopic alteration to the Z-line definitely linked to longstanding GER symptoms was the presence of obvious tongues of metaplastic columnar epithelium (ZAP II/III).     

Diagnosis and Endoscopic Management of Barrett’s Esophagus: an Italian Experts’ Opinion based document

BackgroundBarrett’s esophagus (BE) is recognized as a risk factor for esophageal adenocarcinoma. An expert panel was organized in Italy with the aim of drafting a series of statements on BE to guide diagnosis and management of patients with BE.MethodsThe working Group Coordinators worked on a literature search to identify key topics regarding critical steps of the endoscopic approach to BE. Based on the search and their expert opinion, a list of most meaningful questions was prepared and emailed to all members who were asked to vote the questions. When the survey was completed a consensus meeting was organized. According to the survey results, Group Coordinators proposed a draft statement that was voted. By definition, the statement was formulated when there was an agreement of ≥50% among participants.ResultsTwenty nine participants deliberated 18 questions. The agreement was reached for 16 questions for which a recommendation was formulated.ConclusionThe generated statements highlight the Italian contribution to the European Position Statement of the European Society of Gastrointestinal Endoscopy. The Italian statements preserve peculiarities when dealing with the endoscopic management of BE and wishes to be considered as a contribution for the care of BE patients even with a low risk of progression to esophageal neoplasia.     

The role of inflammation in cancer of the esophagus

Esophageal adenocarcinoma is the eighth most common malignancy worldwide. The overall prognosis is poor, with 5-year survival ranges of approximately 15–25%, and 30–50% for patients who can be treated with curative intent. There has been a marked increase in incidence of esophageal adenocarcinoma over the last 30 years, with chronic and severe reflux, diet and obesity identified as principal factors fuelling this rise in the West. Esophageal adenocarcinoma is an exemplar model of an inflammation-associated cancer. The key molecular pathways driving tumor development and influencing tumor biology are the subject of considerable research efforts, and is the principal focus of this review. In addition, the diverse range of changes occurring in the local immune response, tissue microenvironment, metabolic profile, intracellular signaling mechanisms and microRNA signatures are discussed, as well as novel targeted therapies.     

FABP1 and Hepar expression levels in Barrett’s esophagus and associated neoplasia in an Asian population

IntroductionBarrett's esophagus (BE) is a premalignant condition associated with esophageal adenocarcinoma (EAC). Evidence highlights that EAC is associated with an estimated 5-year survival of approximately 10–15%. Therefore, there is a need to determine which biomarkers are of value in the diagnosis of BE and beyond. The aim of our study was to evaluate the clinical significance of markers known to be expressed across BE and associated neoplasia.MethodsRetrospective tissues were obtained from columnar lined esophagus (CLE) without goblet cells (n = 22), BE (n = 29), dysplasia (n = 14), and EAC (n = 10). Standardised immunohistochemistry for FABP1, Hepar, CDH17, and CDX2 were performed followed by quantitative staining and statistical analysis.ResultsFABP1 expression was negligible in CLE and was highest in BE, with a further decrease in expression in dysplasia and EAC. Hepar expression was also negligible in CLE and was highest in dysplasia and BE, with a reduced expression in EAC. CDH17 and CDX2 showed a significantly higher expression in BE, dysplasia, and EAC compared to CLE.ConclusionAll 4 markers were excellent diagnostic panels to clearly discriminate BE from CLE. Moreover, as FABP1 and Hepar have different expression levels in dysplasia and EAC, these markers could function as key diagnostic aids in helping to determine the state of disease progression.     

Advanced imaging in surveillance of Barrett's esophagus: Is the juice worth the squeeze?

Esophageal cancer is on the rise. The known precursor lesion is Barrett's esophagus(BE). Patients with dysplasia are at higher risk of developing esophageal cancer. Currently the gold standard for surveillance endoscopy involves taking targeted biopsies of abnormal areas as well as random biopsies every 1-2 cm of the length of the Barrett's. Unfortunately studies have shown that this surveillance can miss dysplasia and cancer. Advanced imaging technologies have been developed that may help detect dysplasia in BE. This opinion review discusses advanced imaging in BE surveillance endoscopy and its utility in clinical practice.     

Ghrelin在食管腺癌、Barrett’s食管黏膜中的表达

目的:研究Ghrelin在食管腺癌、Barrett’s食管(barrett esophagus,BE)和正常食管黏膜中的表达.方法:选取30例食管腺癌患者、35例BE患者及35例健康对照,所有受试者均行胃镜检查,记录内镜下表现,在食管部位四象限活检取材,标本经10%甲醛固定,石蜡包埋,连续切片,分别用于改良HE染色及免疫组织化学,采用免疫组织化学方法检测Ghrelin在食管黏膜组织中的表达水平.结果:Ghrelin在食管腺癌组食管黏膜中的表达水平低于健康对照组和BE组,在BE组食管黏膜中的表达高于健康对照组,差异有统计学意义(1.34±0.51vs4.86±0.82vs3.54±0.79,F=27.21,P<0.05).食管腺癌组中,Ghrelin在中高分化腺癌患者食管黏膜的表达水平高于低分化腺癌,差异有统计学意义(Z=4.60,P<0.05).结论:Ghrelin在BE、食管腺癌黏膜中的表达不同,提示了Ghrelin在食管癌变前和癌变后的变化.食管腺癌组织恶变过程中其Ghrelin的分泌机制发生了改变,且与食管腺癌细胞分化程度有关.     

Endoscopic eradication therapy for Barrett’s esophagus: Adverse outcomes,patient values,and cost-effectiveness

Endoscopic therapy for Barrett’s esophagus (BE) aims to replace dysplastic BE epithelium with neosquamous epithelium to prevent and reduce the risk of progression to esophageal adenocarcinoma (EAC) and treat early-stage EAC. Various modalities of endotherapy of dysplastic BE are described. Although endoscopic therapy is safe and effective in treating subjects with intramucosal carcinoma (IMCa), high-grade dysplasia (HGD), and confirmed low-grade dysplasia (LGD), challenges to successful treatment are being recognized. Though adverse outcomes of endotherapy such as bleeding, perforation, pain, and stricture formation are observed, they are not common and can usually be treated medically or endoscopically. Patient values and preferences toward endoscopic therapy and the cost-effectiveness of these endoscopic approaches also have crucial implications for the selection of appropriate treatment and subsequent outcomes in patients with BE.     

Proximal and distal esophageal sensitivity is decreased in patients with Barrett's esophagus

AIM: To investigate sensations to multimodal pain stimulation in the metaplastic and normal parts of the esophagus in patients with Barrett’s esophagus (BE).METHODS: Fifteen patients with BE and 15 age-matched healthy volunteers were subjected to mechanical, thermal and electrical pain stimuli of the esophagus. Both the metaplastic part and the normal part (4 and 14 cm, respectively, above the esophago-gastric junction) were examined. At sensory thresholds the stimulation intensity, referred pain areas, and evoked brain potentials were recorded.RESULTS: Patients were hyposensitive to heat stimulation both in the metaplastic part [median stimulation time to reach the pain detection threshold: 15 (12-34) s vs 14 (6-23) s in controls; F = 4.5, P = 0.04] and the normal part of the esophagus [median 17 (6-32) s vs 13 (8-20) s in controls; F = 6.2, P = 0.02]. Furthermore, patients were hyposensitive in the metaplastic part of the esophagus to mechanical distension [median volume at moderate pain: 50 (20-50) mL vs 33 (13-50) mL in controls; F = 5.7, P = 0.02]. No indication of central nervous system abnormalities was present, as responses were comparable between groups to electrical pain stimuli in the metaplastic part [median current evoking moderate pain: 13 (6-26) mA vs 12 (9-24) mA in controls; F = 0.1, P = 0.7], and in the normal part of the esophagus [median current evoking moderate pain: 9 (6-16) mA, vs 11 (5-11) mA in controls; F = 3.4, P = 0.07]. Furthermore, no differences were seen for the referred pain areas (P-values all > 0.3) or latencies and amplitudes for the evoked brain potentials (P-values all > 0.1).CONCLUSION: Patients with BE are hyposensitive both in the metaplastic and normal part of esophagus likely as a result of abnormalities affecting peripheral nerve pathways.     

Cryotherapy in the management of premalignant and malignant conditions of the esophagus

Endoscopic cryotherapy is a relatively new thermal ablative modality used for the treatment of neoplastic lesions of the esophagus. It relies on cycles of rapid cooling and thawing to induce tissue destruction with a cryogen(liquid nitrogen or carbon dioxide) leading to intra and extra-cellular damage. Surgical treatment was once considered the standard therapeutic intervention for neoplastic diseases of the esophagus and is associated with considerable rates of morbidity and mortality. Several trials that evaluated cryotherapy in Barrett's esophagus(BE) associated neoplasia showed reasonable efficacy rates and safety profile. Cryotherapy has also found applications in the treatment of esophageal cancer, both for curative and palliative intent. Cryotherapy has also shown promising results as salvage therapy in cases refractory to radiofrequency ablation treatment. Cryoballoon focal ablation using liquid nitrogen is a novel mode of cryogen delivery which has been used for the treatment of BE with dysplasia and squamous cell carcinoma. Most common side effects of cryotherapy reported in the literature include mild chest discomfort, esophageal strictures and bleeding. In conclusion, cryotherapy is an effective and safe method for the treatment of esophageal neoplastic processes, ranging from early stages of low grade dysplasia to esophageal cancer.     

不同检测方法探讨幽门螺杆菌感染与Barrett食管之间的关系

目的比较不同检测方法显示的幽门螺杆菌(Helicobacter pylori,H.pylori)感染状况与Barrett食管(Barrett’s esophagus,BE)之间的关系。方法随机收集确诊BE患者84例,同期收集无消化道症状的内镜检测阴性的正常体检者84例作为对照。采用快速尿素酶法、病理中性复红染色法及13C呼气法分别检测患者的幽门螺杆菌感染情况,并收集患者的临床病理资料进行统计学分析。结果快速尿素酶法或病理中性复红染色法检测H.pylori阳性的患者BE组食管下段黏膜阳性率为14.3%(12/84),胃窦部黏膜阳性率为45.2%(38/84),对照组食管下段黏膜及胃窦部黏膜H.pylori阳性率分别为16.7%(14/84)、61.9%(52/84);13C呼气试验检测H.pylori阳性的患者BE组为64.3%(54/84),对照组为66.7%(56/84)。快速尿素酶法或病理中性复红染色法检测食管下段黏膜H.pylori阳性率BE组与对照组比较无显著差异(P>0.05),胃窦黏膜H.pylori阳性率在两组间有显著差异(P<0.05);13C呼气法显示BE组与对照组H.pylori阳性率无显著差异(P>0.05)。结论快速尿素酶法及病理中性复红染色法显示胃窦部H.pylori感染对BE可能具有保护作用,而13C呼气试验显示H.pylori感染可能对BE不具有保护作用,两者的确切关系尚需要进行大样本、多因素的深入研究。     

Biomarkers in Barrett’s esophagus and esophageal adenocarcinoma:Predictors of progression and prognosis

Barrett’s esophagus is a well-known premalignant lesion of the lower esophagus that is characterized by intestinal metaplasia of the squamous epithelium. It is clinically important due to the increased risk (0.5% per annum) of progression to esophageal adenocarcinoma (EA), which has a poor outcome unless diagnosed early. The current clinical management of Barrett’s esophagus is hampered by the lack of accurate predictors of progression. In addition, when patients develop EA, the current staging modalities are limited in stratifying patients into different prognostic groups in order to guide the optimal therapy for an individual patient. Biomarkers have the potential to improve radically the clinical management of patients with Barrett’s esophagus and EA but have not yet entered mainstream clinical practice. This is in contrast to other cancers like breast and prostate for which biomarkers are utilized routinely to inform clinical decisions. This review aims to highlight the most promising predictive and prognostic biomarkers in Barrett’s esophagus and EA and to discuss what is required to move the field forward towards clinical application.     

Endoscopic cryotherapy: Indications,techniques, and outcomes involving the gastrointestinal tract

Endoscopic cryotherapy is a technique utilized for the ablation of target tissue within the gastrointestinal tract. A cryotherapy system utilizes the endoscopic application of cryogen such as liquid nitrogen, carbon dioxide or liquid nitrous oxide. This leads to disruption of cell membranes, apoptosis, and thrombosis of local blood vessels within the target tissue. Several trials utilizing cryotherapy for Barrett’s esophagus (BE) with variable dysplasia, gastric antral vascular ectasia (GAVE), esophageal carcinoma, radiation proctitis, and metastatic esophageal carcinomas have shown safety and efficacy. More recently, liquid nitrogen cryotherapy (cryodilation) was shown to be safe and effective for the treatment of a benign esophageal stricture which was refractory to dilations, steroid injections, and stenting. Moreover, liquid nitrogen cryotherapy is associated with less post procedure pain as compared to radiofrequency ablation in BE with comparable ablation rates. In patients with GAVE, cryotherapy was found to be less tedious as compared to argon plasma coagulation. Adverse events from cryotherapy most commonly include chest pain, esophageal strictures, and bleeding. Gastric perforations did occur as well, but less often. In summary, endoscopic cryotherapy is a promising and growing field, which was first demonstrated in BE, but the use now spans for several other disease processes. Larger randomized controlled trials are needed before its role can be established for these different diseases.     

Global epidemiology of Barrett’s esophagus

Barrett’s esophagus (BE) is defined as a metaplastic change of the distal esophageal epithelium from squamous to columnar type epithelium with the presence of intestinal metaplasia. There is a striking geographic variation in the prevalence rates of BE. Most epidemiological data on BE are derived from patients undergoing endoscopy and do not reflect prevalence rates in the general population. BE is much more common in the West when compared with Asia and Africa. Although BE is less common in Asia, the demographics are similar to the West, being predominantly found in older men with longer duration of reflux symptoms. Some studies from the West have suggested an increase in prevalence rates of BE. An increase in prevalence rates will have significant implications for health resource utilization and costs, due to the small but significant risk of developing esophageal adenocarcinoma. Endoscopic surveillance with the aim of detecting early lesions has been advocated. Compared with conventional white-light endoscopy with blind four-quadrant biopsies, the use of image-enhanced endoscopy, including chromoendoscopy, may improve detection of subtle mucosal irregularities and facilitate targeted biopsies. However, a truly cost-effective surveillance strategy remains to be determined.     

阿司匹林对酸和胆盐诱导的Barrett食管患者食管鳞状细胞NF-κB活化和CDX2表达的影响

目的探讨阿司匹林对酸和胆盐诱导的Barrett食管(Barrett’s esophagus,BE)患者食管鳞状细胞NF-κB活化和CDX2表达的影响。方法将合并BE的胃食管反流病(gastroesophageal reflux disease,GERD)患者的食管鳞状细胞(NES-B细胞)和无合并BE的GERD患者的食管鳞状细胞(NES-G细胞)暴露于酸和胆盐中,分别加入和不加入阿司匹林。采用蛋白质印迹法检测细胞内p65、p-p65、p50、IκB、p-IκB的蛋白表达;染色质免疫沉淀法检测p50和p65与CDX2启动子DNA的结合活性;荧光素酶报告基因检测NF-κB/p65的转录活性;免疫荧光技术检测p65蛋白的核转位情况;qRT-PCR法检测CDX2 mRNA的表达。结果NES-B和NES-G细胞在酸和胆盐暴露后均能激活NF-κB,但与NES-G细胞相比,NES-B细胞表现出更高水平的IκB和p65磷酸化,以及更强的NF-κB转录活性。阿司匹林阻断了酸和胆盐诱导的NES-B细胞中IκB磷酸化、p65核转位、CDX2启动子激活和CDX2表达。结论阿司匹林对酸和胆盐诱导的BE患者食管鳞状细胞NF-κB活化和CDX2表达具有抑制作用。     

Barrett’s esophagus: can biomarkers predict progression to malignancy?

Barrett’s esophagus (BE) is one of the most common premalignant lesions and can progress to esophageal adenocarcinoma. It is characterized histologically by a specialized intestinal metaplasia that replaces the squamous epithelium of the distal esophagus, and is associated with chronic gastroesophageal reflux disease and obesity. Similar to the adenoma–carcinoma sequence of colorectal carcinomas, esophageal adenocarcinoma develops through progression from BE to low- and high-grade dysplasia, then to adenocarcinoma with accumulation of genetic and epigenetic abnormalities. The exact malignancy potential of BE is uncertain. Dysplasia is the most predictive marker for risk of esophageal adenocarcinoma, whereas endoscopic and histological diagnoses are still the gold standard for surveillance of patients with BE. However, both are limited, either by sampling errors in biopsies or by differences in histological interpretation. Several studies have identified candidate biomarkers that may have predictive value and may serve as additional factors for the risk assessment of esophageal adenocarcinoma. This review discusses the role of biomarkers in the progression from BE to adenocarcinoma, focusing on clinical and molecular markers.