Photodynamic therapy vs radiofrequency ablation for Barrett’s dysplasia: Efficacy,safety and cost-comparison

AIM:To compare effectiveness,safety,and cost of photodynamic therapy(PDT)and radiofrequency ablation(RFA)in treatment of Barrett’s dysplasia(BD).METHODS:Consecutive case series of patients undergoing either PDT or RFA treatment at single center by a single investigator were compared.Thirty-three patients with high-grade dysplasia(HGD)had treatment with porfimer sodium photosensitzer and 630 nm laser(130 J/cm),with maximum of 3 treatment sessions.Fifty-three patients with BD(47 with low-grade dysplasia-LGD,6 with HGD)had step-wise circumferential and focal ablation using the HALO system with maximum of 4 treatment sessions.Both groups received proton pump inhibitors twice daily.Endoscopic biopsies were acquired at 2 and 12 mo after enrollment,with 4-quadrant biopsies every 1 cm of the original BE extent.A complete histological resolution response of BD(CR-D)was defined as all biopsies at the last endoscopy session negative for BD.Fisher’s exact test was used to assess differences between the two study groups for primary outcomes.For all outcomes,a two-sided P value of less than 0.05 was considered to indicate statistical significance.RESULTS:Thirty(91%)PDT patients and 39(74%)RFA were men(P=0.05).The mean age was 70.7±12.2 and 65.4±12.7(P=0.10)year and mean length of BE was 5.4±3.2 cm and 5.7±3.2 cm(P=0.53)for PDT and RFA patients,respectively.The CR-D was(18/33)54.5%with PDT vs(47/53)88.7%with RFA(P=0.001).One patient with PDT had an esophageal perforation and was managed with non-surgical measures and no perforation was seen with RFA.PDT was five times more costly than RFA at our institution.The two groups were not randomized and had different BD grading are the limitations of the study.CONCLUSION:In our experience,RFA had higher rate of CR-D without any serious adverse events and was less costly than PDT for endoscopic treatment of BD.     

Treatment of dysplastic Barrett’s Oesophagus in lower volume centres after structured training

AIM: To investigate whether dysplastic Barrett’s Oesophagus can be safely and effectively treated endoscopically in low volume centres after structured training. METHODS: After attending a structured training program in Amsterdam on the endoscopic treatment of dysplastic Barrett’s Oesophagus, treatment of these patients was initiated at St Marys Hospital. This is a retrospective case series conducted at a United Kingdom teaching Hospital, of patients referred for endoscopic treatment of Barrett’s oesophagus with high grade dysplasia or early cancer, who were diagnosed between January 2008 and February 2012. Data was collected on treatment provided(radiofrequency ablation and endoscopic resection), and success of treatment both at the end of treatment and at follow up. Rates of immediate and long term complications were assessed. RESULTS: Thirty-two patients were referred to St Marys with high grade dysplasia or intramucosal cancer within a segment of Barrett’s Oesophagus. Twentyseven met the study inclusion criteria, 16 of these had a visible nodule at initial endoscopy. Treatment was given over a median of 5 mo, and patients received a median of 3 treatment sessions over this time. At the end of treatment dysplasia was successfully eradicated in 96% and intestinal metaplasia in 88%, on per protocol analysis. Patients were followed up for a median of 18 mo. At which time complete eradication of dysplasia was maintained in 86%. Complications were rare: 2 patients suffered from post-procedural bleeding, 4 cases were complicated by oesophageal stenosis. Recurrence of cancer was seen in 1 case. CONCLUSION: With structured training good outcomes can be achieved in low volume centres treating dysplastic Barrett’s Oesophagus.     

Endoscopic treatment of Barrett’s esophagus:From metaplasia to intramucosal carcinoma

The annual incidence of adenocarcinoma arising from Barrett’s esophagus (BE) is approximately 0.5%. Through a process of gradual transformation from lowgrade dysplasia to high-grade dysplasia (HGD), adenocarcinoma can develop in the setting of BE. The clinical importance of appropriate identifi cation and treatment of BE in its various stages, from intestinal metaplasia to intramucosal carcinoma (IMC) hinges on the dramatically different prognostic status between early neoplasia and more advanced stages. Once a patient has symptoms of adenocarcinoma, there is usually locally advanced disease with an approximate 5-year survival rate of about 20%. Esophagectomy has been the gold standard treatment for BE with HGD, due to the suspected risk of harboring occult invasive carcinoma, which was traditionally estimated to be as high as 40%. In recent years, the paradigm of BE early neoplasia management has recently evolved, and endoscopic therapies (endoscopic mucosal resection, radiofrequency ablation, and cryotherapy) have entered the clinical forefront as acceptable non-surgical alternatives for HGD and IMC. The goal of endoscopic therapy for HGD or IMC is to ablateall BE epithelium (both dysplastic and non-dysplastic) due to risk of synchronous/metachronous lesion development in the remaining BE segment.     

Risk factors associated with Barrett’s epithelial dysplasia

AIM:To elucidate risk factors associated with dysplasia of short-segment Barrett’s esophagus(BE).METHODS:A total of 151 BE patients who underwent endoscopic examination from 2004 to 2008 in Aoyama Hospital,Tokyo Women’s Medical University,Japan and whose diagnosis was confirmed from biopsy specimens were enrolled in the study.BE was diagnosed based on endoscopic findings of gastric-appearing mucosa or apparent columnar-lined esophagus proximal to the esophagogastric junction.Dysplasia was classified into three grades-mild,moderate and severe-according to the guidelines of the Vienna Classification System for gastrointestinal epithelial neoplasia.Anthropometric and biochemical data were analyzed to identify risk factors for BE dysplasia.The prevalence of Helicobacter pylori(H.pylori)infection and the expression of p53 by immunohistological staining were also investigated.RESULTS:Histological examination classified patients into three types:specialized columnar epithelium(SCE)(n=65);junctional(n=38);and gastric fundic(n =48).The incidence of dysplasia or adenocarcinoma from BE of the SCE type was significantly higher than that of the other two types(P<0.01).The univariate analysis revealed that sex,H.pylori infection,body weight,p53 overexpression,and low diastolic blood pressure(BP)were associated with BE dysplasia.In contrast,body mass index,waist circumference,metabolic syndrome complications,and variables related to glucose or lipid metabolism were not associated with dysplasia.Multivariate logistic analysis showed that overexpression of p53[odds ratio(OR)=13.1,P=0.004],H.pylori infection(OR=0.19,P=0.066),and diastolic BP(OR=0.87,P=0.021)were independent risk factors for epithelial dysplasia in BE patients with the SCE type.CONCLUSION:Overexpression of p53 is a risk factor for dysplasia of BE,however,H.pylori infection and diastolic BP inversely associated with BE dysplasia might be protective.     

Esophageal resection for high-grade dysplasia and intramucosal carcinoma: When and how?

High-grade dysplasia (HGD) and intramucosal carcinoma (IMC) in the setting of Barrett’s esophagus have traditionally been treated with esophagectomy. However, with the advent of endoscopic mucosal resection and endoscopic ablative therapies, endoscopic therapy at centers with expertise is now an established treatment of Barrett’s-esophagus-related neoplasia, including HGD and IMC. Esophagectomy is today reserved for more selected cases with submucosal invasion, evidence for lymph node metastasis, or unsuccessful endoscopic therapy.     

Raman spectroscopy for early real-time endoscopic optical diagnosis based on biochemical changes during the carcinogenesis of Barrett’s esophagus

Raman spectroscopy is a spectroscopic technique based on the inelastic scattering of monochromatic light that represents the molecular composition of the interrogated volume to provide a direct molecular fingerprint. Several investigations have revealed that confocal Raman spectroscopy can differentiate non-dysplastic Barrett’s esophagus from esophageal high-grade dysplasia and adenocarcinoma with high sensitivity and specificity. An automated on-line Raman spectral diagnostic system has made it possible to use Raman spectroscopy to guide accurate target biopsy instead of multiple random forceps-biopsies,this novel system is expected to improve in vivo precancerous diagnosis and tissue characterization of Barrett’s esophagus.     

Radical excision of Barrett’s esophagus and complete recovery of normal squamous epithelium

To treat Barrett’s esophagus(BE),radiofrequency ablation or cryotherapy are effective treatments for eradicating BE with dysplasia and intestinal metaplasia,and reduce the rates of Barrett’s esophageal adenocarcinoma(BAC).However,patients with BE and dysplasia or early cancer who achieved complete eradication of intestinal metaplasia,BE recurred in 5% within a year,requiring expensive endoscopic surveillances.We performed endoscopic submucosal dissection as complete radically curable treatment procedure for BE with dysplasia,intestinal metaplasia and BAC.     

Endoscopic resection techniques and ablative therapies for Barrett's neoplasia

Esophageal adenocarcinoma is the most rapidly increas- ing cancer in western countries.High-grade dysplasia (HGD)arising from Barrett’s esophagus(BE)is the most important risk factor for its development,and when it is present the reported incidence is up to 10% per patient-year.Adenocarcinoma in the setting of BE develops through a well known histological sequence,from non-dysplastic Barrett’s to low grade dysplasia and then HGD and cancer.Endoscopic surveillance programs have been established to detect the presence of neo- plasia at a potentially curative stage.Newly developed endoscopic treatments have dramatically changed the therapeutic approach of BE.When neoplasia is confined to the mucosal layer the risk for developing lymph node metastasis is negligible and can be successfully eradi- cated by an endoscopic approach,offering a curative in- tention treatment with minimal invasiveness.Endoscopic therapies include resection techniques,also known as tissue-acquiring modalities,and ablation therapies or non-tissue acquiring modalities.The aim of endoscopic treatment is to eradicate the whole Barrett’s segment,since the risk of developing synchronous and metachro- nous lesions due to the persistence of molecular aberra- tions in the residual epithelium is well established.     

Barrett’s食管漏诊1例报道

病例 患者,男,65岁。因“上腹部胀痛4年,加重伴烧心6月”于2007年8月27日入院。外院胃镜示胃窦上皮内瘤变,病检示（胃窦）黏膜慢性炎伴轻度肠化,腺上皮轻度不典型增生。体检：上腹部轻度压痛。     

Single hepatocellular carcinoma ≤ 3 cm in left lateral segment: Liver resection or radiofrequency ablation?

AIM:To evaluate the long-term results of radiofrequency ablation(RFA)compared to left lateral sectionectomy(LLS)in patients with Child-Pugh class A disease for the treatment of single and small hepatocellular carcinoma(HCC)in the left lateral segments.METHODS:We retrospectively reviewed the data of133 patients with single HCC(≤3 cm)in their left lateral segments who underwent curative LLS(n=66)or RFA(n=67)between 2006 and 2010.RESULTS:The median follow-up period was 33.5mo in the LLS group and 29 mo in the RFA group(P=0.060).Most patients had hepatitis B virus-related HCC.The hospital stay was longer in the LLS group than in the RFA group(8 d vs 2 d,P<0.001).The 1-,2-,and 3-year disease-free survival and overall survival rates were 80.0%,68.2%,and 60.0%,and 95.4%,92.3%,and 92.3%,respectively,for the LLS group;and 80.8%,59.9%,and 39.6%,and 98.2%,92.0%,and 74.4%,respectively,for the RFA group.The disease-free survival curve and overall survival curve were higher in the LLS group than in the RFA group(P=0.012 and P=0.013,respectively).Increased PIVKA-Ⅱlevels and small tumor size were associated with HCC recurrence in multivariate analysis.CONCLUSION:Liver resection is suitable for single HCC≤3 cm in the left lateral segments.     

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.     

Barrett’s食管微创治疗的研究进展

Barrett’s食管(Barrett’s esophagus,BE)是公认的癌前病变,高度异型增生(high-grade dysplasia,HGD)的出现是进展为食管腺癌的关键.在我国食管腺癌的发生率正呈快速上升趋势.因此对BE中出现HGD患者的治疗引起了广泛重视.随着医疗技术及医疗科技的发展,各种微创治疗方法不断涌现,但由于治疗方法的个体化,及缺乏远期效果的评估,对大部分患者来说治疗方法的选择还没有明确的指南.本篇综述的目的是简单介绍各种内镜治疗方法,比较这些方法的治疗效果,分析影响治疗效果的相关因素,以期为该病的治疗提供指导.     

Era of Barrett’s surveillance: Does equipment matter?

Barrett’s esophagus is a consequence of long standing gastro-esophageal reflux disease and predisposes to the development of esophageal adenocarcinoma. Regular surveillance endoscopies can detect curable early neoplasia in asymptomatic patients, which in turn could improve the prognosis compared to symptomatic cancer. Early neoplastic lesions, which are amenable for local therapy, could be treated endoscopically, avoiding a major surgery. However, in the absence of obvious mucosal lesions, random four quadr...     

Psychosocial factors and their association with reflux oesophagitis,Barrett’s oesophagus and oesophageal adenocarcinoma

AIM:To investigate the role of psychological characteristics as risk factors for oesophageal adenocarcinoma(OAC),as well as the reflux-mediated precursor pathway.METHODS:An all-Ireland population-based case-control study recruited 230 reflux oesophagitis(RO),224 Barrett’s oesophagus(BO) and 227 OAC patients and 260 controls.Each case/control group completed measures of stress,depression,self-efficacy,self-esteem,repression and social support.A comparative analysis was undertaken using polytomous logistic regression adjusted for potential confounders.RESULTS:Compared to controls,OAC patients were almost half as likely to report high stress levels over their lifetime(P = 0.010,OR 0.51;95%CI:0.29-0.90)and 36% less likely to report having experienced depression(OR 0.64;95%CI:0.42-0.98).RO patients reported significantly higher stress than controls particularly during middle-and senior-years(P for trends < 0.001).RO patients were 37% less likely to report having been highly emotionally repressed(OR 0.63;95%CI:0.41-0.95).All case groups(OAC,RO and BO) were more likely than controls to report having had substantial amounts of social support(OR 2.84;95%CI:1.63-4.97;OR 1.97;95%CI:1.13-3.44 and OR 1.83;95%CI:1.03-3.24,respectively).CONCLUSION:The improved psychological profile of OAC patients may be explained by response shift.The role of psychological factors in the development of OAC requires further investigation.     

Endocytoscopic visualization of squamous cell islands within Barrett’s epithelium

AIM: To study the endocytoscopic visualization of squamous cell islands within Barrett’s epithelium. METHODS: Endocytoscopy (ECS) has been studied in the surveillance of Barrett’s esophagus, with controversial results. In initial studies, however, a soft catheter type endocytoscope was used, while only methylene blue dye was used for the staining of Barrett’s mucosa. Integrated type endocytoscopes (GIF-Q260 EC, Olympus Corp, Tokyo, Japan) have been recently developed, with the incorporation of a high-power magnifying endocytoscope into a standard endoscope together with narrow-band imaging (NBI). Moreover, double staining with a mixture of 0.05% crystal violet and 0.1% of methylene blue (CM) during ECS enables higher quality images comparable to conventional hematoxylin eosin histopathological images.RESULTS: In vivo endocytoscopic visualization of papillary squamous cell islands within glandular Barrett’s epithelium in a patient with long-segment Barrett’s esophagus is reported. Conventional white light endoscopy showed typical long-segment Barrett’s esophagus, with small squamous cell islands within normal Barrett’s mucosa, which were better visualized by NBI endoscopy. ECS after double CM staining showed regular Barrett’s esophagus, while higher magnification (×480) revealed the orifices of glandular structures better. Furthermore, typical squamous cell papillary protrusion, classified as endocytoscopic atypia classification (ECA) 2 according to ECA, was identified within regular glandular Barrett’s mucosa. Histological examination of biopsies taken from the same area showed squamous epithelium within glandular Barrett’s mucosa, corresponding well to endocytoscopic findings. CONCLUSION: To our knowledge, this is the first report of in vivo visualization of esophageal papillary squamous cell islands surrounded by glandular Barrett’s epithelium.     

Meta-analysis of Barrett’s esophagus in China

AIM:To investigate the epidemiology and characteristics of Barrett’s esophagus(BE)in China and compare with cases in the west.METHODS:Studies were retrieved from the China National Knowledge Infrastructure and PubMed databases using the terms"Barrett"and"Barrett AND China",respectively,as well as published studies about BE in China from 2000 to 2011.The researchers reviewed the titles and abstracts of all search results to determine whether or not the literature was relevant to the current topic of this research.The references listed in the studies were also searched.Inclusion and exclusion criteria for the literature were appropriately established,and the data reported in the selected studies were analyzed.Finally,a meta-analysis was performed.RESULTS:The current research included 3873 cases of BE from 69 studies.The endoscopic detection rate of BE in China was 1%.The ratio of male to female cases was 1.781 to 1,and the average age of BE patients was 49.07±5.09 years.Island-type and shortsegment BE were the most common endoscopic manifestations,accounting for 4.48%and 80.3%,respectively,of all cases studied.Cardiac-type BE was observed in 40.0%of the cases,representing the most common histological characteristic of the condition.Cancer incidence was 1.418 per 1000 person-years.CONCLUSION:Average age of BE patients in China is lower than in Western countries.Endoscopic detection and cancer incidence were also lower in China.     

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 mucosal resection of large hyperplastic polyps in 3 patients with Barrett’s esophagus

INTRODUCTION Benign esophageal tumors are rare, representing less than 1% of all esophageal tumors[1]. They are usually asymptomatic and often discovered incidentally[2]. Many classifications have been proposed for benign esophageal tumors: by histologica…