Endoscopic imaging of Barrett’s esophagus

The incidence of esophageal adenocarcinoma(EAC) has dramatically increased in the United States as well as Western European countries. The majority of esophageal adenocarcinomas arise from a backdrop of Barrett’s esophagus(BE),a premalignant lesion that can lead to dysplasia and cancer. Because of the increased risk of EAC,GI society guidelines recommend endoscopic surveillance of patients with BE. The emphasis on early detection of dysplasia in BE through surveillance endoscopy has led to the development of advanced endoscopic imaging technologies. These techniques have the potential to both improve mucosal visualization and characterization and to detect small mucosal abnormalities which are difficult to identify with standard endoscopy. This review summarizes the advanced imaging technologies used in evaluation of BE.     

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.     

Effect of medical and surgical treatment of Barrett’s metaplasia

Barrett’s esophagus (BE) is a change in the esophageal mucosa as a result of long-standing gastroesophageal reflux disease. The importance of BE is that it is the main risk factor for the development of esophageal adenocarcinoma, whose incidence is currently growing faster than any other cancer in the Western world. The aim of this review was to compare the common treatment modalities of BE, with the focus on proton pump inhibitors and operative fundoplication. We performed a literature search on medical and surgical treatment of BE to determine eligible studies for this review. Studies on medical and surgical treatment of BE are discussed with regard to treatment effect on progression and regression of disease. Although there is some evidence for control of reflux with either medical or surgical therapy, there is no def initive evidence that either treatment modality decreases the risk of progression to dysplasia or cancer. Even though there is a trend toward antireflux surgery being superior, there are no def initive studies to prove this.     

Clinical significance and management of Barrett's esophagus with epithelial changes indefinite for dysplasia

Barrett's esophagus(BE) is defined as the extension of salmon-colored mucosa into the tubular esophagus ≥1 cm proximal to the gastroesophageal junction with biopsy confirmation of intestinal metaplasia. Patients with BE are at increased risk of esophageal adenocarcinoma(EAC), and undergo endoscopic surveillance biopsies to detect dysplasia or early EAC. Dysplasia in BE is classified as no dysplasia, indefinite for dysplasia(IND), low grade dysplasia(LGD) or high grade dysplasia(HGD). Biopsies are diagnosed as IND when the epithelial abnor-malities are not sufficient to diagnose dysplasia or the nature of the epithelial abnormalities is uncertain due to inflammation or technical issues. Specific diagnostic criteria for IND are not well established and its clinical significance and management has not been well studied. Previous studies have focused on HGD in BE and led to changes and improvement in the management of BE with HGD and early EAC. Only recently, IND and LGD in BE have become focus of intense study. This review summarizes the definition, neoplastic risk and clinical management of BE IND.     

Barrett's esophagus in 2016: From pathophysiology to treatment

Esophageal complications caused by gastroesophageal reflux disease(GERD)include reflux esophagitis and Barrett’s esophagus(BE).BE is a premalignant condition with an increased risk of developing esophageal adeno-carcinoma(EAC).The carcinogenic sequence may progress through several steps,from normal esophageal mucosa through BE to EAC.A recent advent of functional esophageal testing(particularly multichannel intraluminal impedance and pH monitoring)has helped to improve our knowledge about GERD pathophysiology,including its complications.Those findings(when properly confirmed)might help to predict BE neoplastic progression.Over the last few decades,the incidence of EAC has continued to rise in Western populations.However,only a minority of BE patients develop EAC,opening the debate regarding the cost-effectiveness of current screening/surveillance strategies.Thus,major efforts in clinical and research practice are focused on new methods for optimal risk assessment that can stratify BE patients at low or high risk of developing EAC,which should improve the cost effectiveness of screening/surveillance programs and consequently significantly affect health-care costs.Furthermore,the area of BE therapeutic management is rapidly evolving.Endoscopic eradication therapies have been shown to be effective,and new therapeutic options for BE and EAC have emerged.The aim of the present review article is to highlight the status of screening/surveillance programs and the current progress of BE therapy.Moreover,we discuss the recent introduction of novel esophageal pathophysiological exams that have improved the knowledge of the mechanisms linking GERD to BE.     

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.     

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 management for congenital esophageal stenosis: A systematic review

Congenital esophageal stenosis(CES) is an extremely rare malformation, and standard treatment have not been completely established. By years of clinical research, evidence has been accumulated. We conducted systematic review to assess outcomes of the treatment for CES, especially the role of endoscopic modalities. A total of 144 literatures were screened and reviewed. CES was categorized in fibromuscularthickening, tracheobronchial remnants(TBR) and membranous web, and the frequency was 54%, 30% and 16%, respectively. Therapeutic option includes surgery and dilatation, and surgery tends to be reserved for ineffective dilatation. An essential point is that dilatation for TBR type of CES has low success rate and high rate of perforation. TBR can be distinguished by using endoscopic ultrasonography(EUS). Overall success rate of dilatation for CES with or without case selection by using EUS was 90% and 29%, respectively. Overall rate of perforation with or without case selection was 7% and 24%, respectively. By case selection using EUS, high success rate with low rate of perforation could be achieved. In conclusion, endoscopic dilatation has been established as a primary therapy for CES except TBR type. Repetitive dilatation with gradual step-up might be one of safe ways to minimize the risk of perforation.     

Cerebral and splenic infarctions after injection of N-butyl-2-cyanoacrylate in esophageal variceal bleeding

Variceal bleeding is the most serious complication of portal hypertension,and it accounts for approximately one fifth to one third of all deaths in liver cirrhosis patients.Currently,endoscopic treatment remains the predominant method for the prevention and treatment of variceal bleeding.Endoscopic treatments include band ligation and injection sclerotherapy.Injection sclerotherapy with N-butyl-2-cyanoacrylate has been successfully used to treat variceal bleeding.Although injection sclerotherapy with N-butyl-2-cyanoacrylate provides effective treatment for variceal bleeding,injection of N-butyl-2-cyanoacrylate is associated with a variety of complications,including systemic embolization.Herein,we report a case of cerebral and splenic infarctions after the injection of N-butyl-2-cyanoacrylate to treat esophageal variceal bleeding.     

Assessment of the diagnostic performance and interobserver variability of endocytoscopy in Barrett’s esophagus:A pilot ex-vivo study

AIM:To investigate a classification of endocytoscopy(ECS)images in Barrett’s esophagus(BE)and evaluate its diagnostic performance and interobserver variability.METHODS:ECS was applied to surveillance endoscopic mucosal resection(EMR)specimens of BE ex-vivo.The mucosal surface of specimen was stained with 1%methylene blue and surveyed with a catheter-type endocytoscope.We selected still images that were most representative of the endoscopically suspect lesion and matched with the final histopathological diagnosis to accomplish accurate correlation.The diagnostic performance and inter-observer variability of the new classification scheme were assessed in a blinded fashion by physicians with expertise in both BE and ECS and inexperienced physicians with no prior exposure to ECS.RESULTS:Three staff physicians and 22 gastroenterology fellows classified eight randomly assigned unknown still ECS pictures(two images per each classification)into one of four histopathologic categories as follows:(1)BEC1-squamous epithelium;(2)BEC2-BE without dysplasia;(3)BEC3-BE with dysplasia;and(4)BEC4-esophageal adenocarcinoma(EAC)in BE.Accuracy of diagnosis in staff physicians and clinical fellows were,respectively,100%and 99.4%for BEC1,95.8%and83.0%for BEC2,91.7%and 83.0%for BEC3,and95.8%and 98.3%for BEC4.Interobserver agreement of the faculty physicians and fellows in classifying each category were 0.932 and 0.897,respectively.CONCLUSION:This is the first study to investigate classification system of ECS in BE.This ex-vivo pilot study demonstrated acceptable diagnostic accuracy and excellent interobserver agreement.     

Endoscopic submucosal dissection and surgical treatment for gastrointestinal cancer

Endoscopic submucosal dissection (ESD) is widely usedin Japan as a minimally invasive treatment for earlygastric cancer. The application of ESD has expanded tothe esophagus and colorectum. The indication criteriafor endoscopic resection (ER) are established for eachorgan in Japan. Additional treatment, including surgery with lymph node dissection, is recommended when pathological examinations of resected specimens donot meet the criteria. Repeat ER for locally recurrent gastrointestinal tumors may be difficult because of submucosal fibrosis, and surgical resection is required inthese cases. However, ESD enables complete resectionin 82%-100% of locally recurrent tumors. Transanal endoscopic microsurgery (TEM) is a well-developed sur-gical procedure for the local excision of rectal tumors.ESD may be superior to TEM alone for superficial rectaltumors. Perforation is a major complication of ESD,and it is traditionally treated using salvage laparotomy.However, immediate endoscopic closure followed byadequate intensive treatment may avoid the need forsurgical treatment for perforations that occur during ESD. A second primary tumor in the remnant stomach after gastrectomy or a tumor in the reconstructedorgan after esophageal resection has traditionally required surgical treatment because of the technical difficulty of ER. However, ESD enables complete resectionin 74%-92% of these lesions. Trials of a combination ofESD and laparoscopic surgery for the resection of gastric submucosal tumors or the performance of sentinellymph node biopsy after ESD have been reported, butthe latter procedure requires a careful evaluation of itsclinical feasibility.     

Endoscopic submucosal dissection for superficial esophageal squamous cell neoplasms

Endoscopic resection is an effective treatment for noninvasive esophageal squamous cell neoplasms(ESCNs).Endoscopic mucosal resection(EMR)has been developed for small localized ESCNs as an alternative to surgical therapy because it shows similar effectiveness and is less invasive than esophagectomy.However,EMR is limited in resection size and therefore piecemeal resection is performed for large lesions,resulting in an imprecise histological evaluation and a high frequency of local recurrence.Endoscopic submucosal dissection(ESD)has been developed in Japan as one of the standard endoscopic resection techniques for ESCNs.ESD enables esophageal lesions,regardless of their size,to be removed en bloc and thus has a lower local recurrence rate than EMR.The development of new devices and the establishment of optimal strategies for esophageal ESD have resulted in fewer complications such as perforation than expected.However,esophageal stricture after ESD may occur when the resected area is larger than three-quarters of the esophageal lumen or particularly when it encompasses the entire circumference;such a stricture requires multiple sessions of endoscopic balloon dilatation.Recently,oral prednisolone has been reported to be useful in preventing post-ESD stricture.In addition,a combination of chemoradiotherapy(CRT)and ESD might be an alternative therapy for submucosal esophageal cancer that has a risk of lymph node metastasis because esophagectomy is extremely invasive;CRT has a higher local recurrence rate than esophagectomy but is less invasive.ESD is likely to play a central role in the treatment of superficial esophageal squamous cell neoplasms in the future.     

Squamous cell carcinoma after radiofrequency ablation for Barrett’s dysplasia

Barrett’s oesophagus(BO)is a usually indolent condition that occasionally requires endoscopic therapy.Radiofrequency ablation(RFA)is an effective endoscopic treatment for high grade dysplasia(HGD)and intramucosal cancer in BO.It has a good efficacy,durability and safety profile although complications can occur.Here we describe a case of RFA in a patient with high grade dysplasia.Although the response to treatment was initially very good with the development of neosquamous epithelium,the patient very rapidly developed a squamous cell cancer of the oesophagus confirmed on radiology,histology and immunohistochemistry.Sanger sequencing confirmed that the original HGD and the squamous cell cancer(SCC)were derived from separate clonal origins.The report highlights the fact that SCC of the oesophagus has been noted after endoscopic ablation for BO previously and suggest that ablation of BO may encourage the clonal expansion of cells carrying carcinogenic mutations once a dominant clonal population has been eradicated.     

Long-term follow-up after complete ablation of Barrett＇s esophagus with argon plasma coagulation

AIM: To report the long-term outcome of patients after complete ablation of non-neoplastic Barrett's esophagus (BE) with respect to BE relapse and development of intraepithelial neoplasia or esophageal adenocarcinoma. METHODS: In 70 patients with historically proven non neoplastic BE, complete BE ablation was achieved by argon plasma coagulation (APC) and high-dose proton pump inhibitor therapy (120 mg omeprazole daily). Sixty-six patients (94.4%) underwent further surveillance endoscopy. At each surveillance endoscopy four-quadrant biopsies were taken from the neo-squamous epithelium at 2 cm intervals depending on the pre-treatment length of BE mucosa beginning at the neo-Z-line, and from any endoscopically suspicious lesion. RESULTS: The median follow-up of 66 patients was 51 mo (range 9-85 mo) giving a total of 280.5 patient years. A mean of 6 biopsies were taken during surveillance endoscopies. In 13 patients (19.7%) tongues or islands suspicious for BE were found during endoscopy. In 8 of these patients (12.1%) non-neoplastic BE relapse was confirmed histologically giving a histological relapse rate of 3% per year. In none of the patients, intraepithelial neoplasia nor an esophageal adenocarcinoma was detected. Logistic regression analysis identified endoscopic detection of islands or tongues as the only positive predictor of BE relapse (P= 0.0004). CONCLUSION: The long-term relapse rate of non neoplastic BE following complete ablation with high-power APC is low (3% per year).     

Endoscopic management of biliary strictures after liver transplantation

Bile duct strictures remain a major source of morbidity after orthotopic liver transplantation （OLT）. Biliary strictures are classified as anastomotic or non-anastomotic strictures according to location and are defined by distinct clinical behaviors. Anastomotic strictures are localized and short. The outcome of endoscopic treatment for anastomotic strictures is excellent. Nonanastomotic strictures often result from ischemic and immunological events, occur earlier and are usually multiple and longer. They are characterized by a far less favorable response to endoscopic management, higher recurrence rates, graft loss and need for retransplantation. Living donor OLT patients present a unique set of challenges arising from technical factors, and stricture risk for both recipients and donors. Endoscopic treatment of living donor OLT patients is less promising. Current endoscopic strategies for biliary strictures after OLT include repeated balloon dilations and placement of multiple side-by-side plastic stents. Lifelong surveillance is required in all types of strictures. Despite improvements in incidence and long term outcomes with endoscopic management, and a reduced need for surgical treatment, the impact of strictures on patients after OLT is significant. Future considerations include new endoscopic technologies and improved stents, which could potentially allow for a decreased number of interventions, increased intervals before retreatment, and decreased reliance on percutaneous and surgical modalities. Thisreview focuses on the role of endoscopy in biliary strictures, one of the most common biliary complications after OLT.     

Current status in remnant gastric cancer after distal gastrectomy

Remnant gastric cancer(RGC) and gastric stump cancer after distal gastrectomy(DG) are recognized as the same clinical entity. In this review, the current knowledges as well as the non-settled issues of RGC are presented. Duodenogastric reflux and denervation of the gastric mucosa are considered as the two main factors responsible for the development of RGC after benign disease. On the other hand, some precancerous circumstances which already have existed at the time of initial surgery, such as atrophic gastritis and intestinal metaplasia, are the main factors associated with RGC after gastric cancer. Although eradication of Helicobacter pylori(H. pylori) in remnant stomach is promising, it is still uncertain whether it can reduce the risk of carcinogenesis. Periodic endoscopic surveillance after DG was reported useful in detecting RGC at an early stage, which offers a chance to undergo minimally invasive endoscopic treatment or laparoscopic surgery and leads to an improved prognosis in RGC patients. Future challenges may be expected to elucidate the benefit of eradication of H. pylori in the remnant stomach if it could reduce the risk for RGC, to build an optimal endoscopic surveillance strategy after DG by stratifying the risk for development of RGC, and to develop a specific staging system for RGC for the standardization of the treatment by prospecting the prognosis.     

Management of gastric subepithelial tumors: The role of endoscopy

With the wide use of esophagogastroduodenoscopy,the incidence of gastric subepithelial tumor(SET)diagnosis has increased.While the management of large orsymptomatic gastric SETs is obvious,treatment of small(≤3 cm)asymptomatic gastric SETs remains inconclusive.Moreover,the presence of gastrointestinal stromal tumors with malignant potential is of concern,and endoscopic treatment of gastric SETs remains a subject of debate.Recently,numerous studies have demonstrated the feasibility of endoscopic treatment of gastric SETs,and have proposed various endoscopic procedures including endoscopic submucosal dissection,endoscopic muscularis dissection,endoscopic enucleation,endoscopic submucosal tunnel dissection,endoscopic full-thickness resection,and a hybrid approach(the combination of endoscopy and laparoscopy).In this review article,we discuss current endoscopic treatments for gastric SETs as well as the advantages and limitations of this type of therapy.Finally,we predict the availability of newly developed endoscopic treatments for gastric SETs.     

Cost-effectiveness analysis of beta-blockers vs endoscopic surveillance in patients with cirrhosis and small varices

AIM:To evaluate the most cost-effectiveness strategy for preventing variceal growth and bleeding in patients with cirrhosis and small esophageal varices.METHODS:A stochastic analysis based on decision trees was performed to compare the cost-effectiveness of beta-blockers therapy starting from a diagnosis of small varices(Strategy 1)with that of endoscopic surveillance followed by beta-blockers treatment when large varices are demonstrated(Strategy 2),for preventing variceal growth,bleeding and death in patients with cirrhosis and small esophageal varices.The basic nodes of the tree were gastrointestinal endoscopy,inpatient admission and treatment for bleeding,as required.All estimates were performed using a Monte Carlo microsimulation technique,consisting in simulating observations from known probability distributions depicted in the model.Eight-hundred-thousand simulations were performed to obtain the final estimates.All estimates were then subjected to Monte Carlo Probabilistic sensitivity analysis,to assess the impact of the variability of such estimates on the outcome distributions.RESULTS:The event rate(considered as progression of varices or bleeding or death)in Strategy 1[24.09%(95%CI:14.89%-33.29%)]was significantly lower than in Strategy 2[60.00%(95%CI:48.91%-71.08%)].The mean cost(up to the first event)associated with Strategy 1[823￡(95%CI:106￡-2036￡)]was not significantly different from that of Strategy 2[799￡(95%CI:0￡-3498￡)].The cost-effectiveness ratio with respect to this endpoint was equal to 50.26￡(95%CI:-504.37￡-604.89￡)per event avoided over the four-year follow-up.When bleeding episodes/deaths in subjects whose varices had grown were included,the mean cost associated with Strategy 1 was 1028￡(95%CI:122￡-2581￡),while 1699￡(95%CI:171￡-4674￡)in Strategy 2.CONCLUSION:Beta-blocker therapy turn out to be more effective and less expensive than endoscopic surveillance for primary prophylaxis of bleeding in patients with cirrhosis and small varices.     

Colorectal cancer surveillance in patients with inflammatory bowel disease: What is new?

Several studies assessing the incidence of colorectal cancer (CRC) in inflammatory bowel disease (IBD) patients have found an increased risk globally estimated to be 2 to 5 times higher than for the general population of the same age group. The real magnitude of this risk, however, is still open to debate. Research is currently being carried out on several risk and protective factors for CRC that have recently been identified in IBD patients. A deeper understanding of these factors could help stratify patient risk and aid specialists in choosing which surveillance program is most efficient. There are several guidelines for choosing the correct surveillance program for IBD patients; many present common characteristics with various distinctions. Current recommendations are far from perfect and have important limitations such as the fact that their efficiency has not been demonstrated through randomized controlled trials, the limited number of biopsies performed in daily endoscopic practice, and the difficulty in establishing the correct time to begin a given surveillance program and maintain a schedule of surveillance. That being said, new endoscopic technologies should help by replacing random biopsy protocols with targeted biopsies in IBD patients, thereby improving the efficiency of surveillance programs.However, further studies are needed to evaluate the cost-effectiveness of introducing these techniques into daily endoscopic practice.