New optical technologies for earlier endoscopic diagnosis of premalignant gastrointestinal lesions

Gastrointestinal malignancies continue to be the second leading cause of cancer-related deaths in the developed world. The early detection and treatment of gastrointestinal preneoplasms has been demonstrated to significantly improve patient survival. Conventional screening tools include standard white light endoscopy (WLE) and frequent surveillance with biopsy. Well-defined endoscopic surveillance biopsy protocols aimed at early detection of dysplasia and malignancy have been undertaken for groups at high risk. Unfortunately, the poor sensitivity associated with WLE is a significant limitation. In this regard, major efforts continue in the development and evaluation of alternative diagnostic techniques. This review will focus on notable developments made at the forefront of research in modern gastrointestinal endoscopy based on novel optical endoscopic modalities, which rely on the interactions of light with tissues. Here we present the 'state - of - the - art' in fluorescence endoscopic imaging and spectroscopy, Raman spectroscopy, optical coherence tomography, light scattering spectroscopy, chromoendoscopy, confocal fluorescence endoscopy, and immunofluorescence endoscopy. These new developments may offer significant improvements in the diagnosis of early lesions by allowing for targeted mucosal excisional biopsies, and perhaps may even provide 'optical biopsies' of equivalent histological accuracy. This enhancement of the endoscopist's ability to detect subtle preneoplastic changes in the gastrointestional mucosa in real time and improved staging of lesions could lead to curative endoscopic ablation of these lesions and, in the long term, improve patient survival and quality of life.     

Endoscopic detection of early upper GI cancers

The detection of early-stage neoplastic lesions in the upper GI tract is associated with improved survival and the potential for complete endoscopic resection that is minimally invasive and less morbid than surgery. Despite technological advances in standard white-light endoscopy, the ability of the endoscopist to reliably detect dysplastic and early cancerous changes in the upper GI tract remains limited. In conditions such as Barrett's oesophagus, practice guidelines recommend periodic endoscopic surveillance with multiple biopsies, a methodology that is hindered by random sampling error, inconsistent histopathological interpretation, and delay in diagnosis. Early detection may be enhanced by several promising diagnostic modalities such as chromoendoscopy, magnification endoscopy, and optical spectroscopic/imaging techniques, as these modalities offer the potential to identify in real-time lesions that are inconspicuous under conventional endoscopy. The combination of novel diagnostic techniques and local endoscopic therapies will provide the endoscopist with much needed tools that can considerably enhance the detection and management of early stage lesions in the upper GI tract.     

Optical biopsy: a new frontier in endoscopic detection and diagnosis.

Endoscopic diagnosis currently relies on the ability of the operator to visualize abnormal patterns in the image created by light reflected from the mucosal surface of the gastrointestinal tract. Advances in fiber optics, light sources, detectors, and molecular biology have led to the development of several novel methods for tissue evaluation in situ. The term "optical biopsy" refers to methods that use the properties of light to enable the operator to make an instant diagnosis at endoscopy, previously possible only by using histological or cytological analysis. Promising imaging techniques include fluorescence endoscopy, optical coherence tomography, confocal microendoscopy, and molecular imaging. Point detection schemes under development include light scattering and Raman spectroscopy. Such advanced diagnostic methods go beyond standard endoscopic techniques by offering improved image resolution, contrast, and tissue penetration and providing biochemical and molecular information about mucosal disease. This review describes the basic biophysics of light-tissue interactions, assesses the strengths and weaknesses of each method, and examines clinical and preclinical evidence for each approach.     

Recent Advances in Light-Induced Fluorescence Endoscopy (LIFE) of the Gastrointestinal Tract

Abstract: Gastrointestinal (GI) cancer continues to be a significant malignant disease. It is well recognized that early detection of dysplastic changes prior to invasive growth may have a pronounced effect on the clinical efficacy of treatment and subsequent patient survival. Standard white-light endoscopic visualization of such early lesions is often difficult and many premalignant lesions remain undetected during routine screening procedures. Additionally, dysplastic lesions are usually not distinguished against surrounding normal tissue, and visible non-adenomatous lesions such as hyperplastic polyps are often indistinguishable from adenomatous polyps. However, recent developments in endoscopic technology have led to the development of more sensitive endoscopic screening methods. Fluorescence-based endoscopic imaging or spectroscopy of the gastrointestinal tract may offer a novel and alternative means of detecting and identifying premalignant and malignant lesions otherwise occult to conventional white-light endoscopy. The purpose of this review is to present a general overview of the current developments and possible clinical roles of light-induced fluorescence endoscopy (LIFE) as an adjunct to conventional diagnostic endoscopy for screening and surveillance for premaligant and malignant gastrointestinal lesions. (Dig Endosc 1999; 11: 108–118)     

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.     

Light-induced autofluorescence spectroscopy for the endoscopic detection of esophageal cancer

BACKGROUND: Any innovative optical system that facilitates the early endoscopic detection of neoplastic change in the GI mucosa has the potential to greatly improve survival and quality of life for patients prone to have GI malignancies develop. The present article describes light-induced autofluorescence spectroscopy with violet-blue excitation light for in vivo diagnosis of cancerous tissue of the esophagus during routine endoscopy. METHODS: One hundred twenty-nine endogenous fluorescence spectra were obtained from normal mucosa and malignant lesions in 9 patients with squamous cell cancer and 4 with adenocarcinoma of the esophagus. Following spectrographic measurements, biopsy specimens were obtained for definitive classification of the spectra. A special light source capable of delivering either white or violet-blue light for excitation of tissue autofluorescence by means of an endoscope was used. Endogenous fluorescence spectra emitted by tissues were detected with a fiberoptic probe and analyzed with a spectrograph. RESULTS: Squamous cell cancer and adenocarcinoma of the esophagus exhibit specific changes in the emitted fluorescence spectra as compared with normal mucosa. Based on the results obtained in earlier studies, malignant and benign spectra were differentiated with the aid of a mathematical algorithm. By using this algorithm, a sensitivity of 97% and specificity of 95% were obtained for the diagnosis of esophageal carcinoma. CONCLUSIONS: Light-induced fluorescence spectroscopy is useful for the endoscopic detection of squamous cell cancer and adenocarcinoma of the esophagus. This spectroscopic study provides a basis for the design of a simplified autofluorescence imaging system for detection of esophageal neoplasms.     

Fluorescence spectroscopy incorporated in an Optical Biopsy System for the detection of early neoplasia in Barrett's esophagus

Endoscopic surveillance is recommended for patients with Barrett's esophagus (BE) to detect high‐grade intraepithelial neoplasia (HGIN) or early cancer (EC). Early neoplasia is difficult to detect with white light endoscopy and random biopsies are associated with sampling error. Fluorescence spectroscopy has been studied to distinguish non‐dysplastic Barrett's epithelium (NDBE) from early neoplasia. The Optical Biopsy System (OBS) uses an optical fiber integrated in a regular biopsy forceps. This allows real‐time spectroscopy and ensures spot‐on correlation between the spectral signature and corresponding physical biopsy. The OBS may provide an easy‐to‐use endoscopic tool during BE surveillance. We aimed to develop a tissue‐differentiating algorithm and correlate the discriminating properties of the OBS with the constructed algorithm to the endoscopist's assessment of the Barrett's esophagus. In BE patients undergoing endoscopy, areas suspicious for neoplasia and endoscopically non‐suspicious areas were investigated with the OBS, followed by a correlating physical biopsy with the optical biopsy forceps. Spectra were correlated to histology and an algorithm was constructed to discriminate between HGIN/EC and NDBE using smoothed linear dicriminant analysis. The constructed classifier was internally cross‐validated and correlated to the endoscopist's assessment of the BE segment. A total of 47 patients were included (39 males, age 66 years): 35 BE patients were referred with early neoplasia and 12 patients with NDBE. A total of 245 areas were investigated with following histology: 43 HGIN/EC, 66 low‐grade intraepithelial neoplasia, 108 NDBE, 28 gastric or squamous mucosa. Areas with low‐grade intraepithelial neoplasia and gastric/squamous mucosa were excluded. The area under the receiver operating characteristic curve of the constructed classifier was 0.78. Sensitivity and specificity for the discrimination between NDBE and HGIN/EC of OBS alone were 81% and 58% respectively. When OBS was combined with the endoscopist's assesssment, sensitivity was 91% and specificity 50%. If this protocol would have guided the decision to obtain biopsies, half of the biopsies would have been avoided, yet 4/43 areas containing HGIN/EC (9%) would have been inadvertently classified as unsuspicious. In this study, the OBS was used to construct an algorithm to discriminate neoplastic from non‐neoplastic BE. Moreover, the feasibility of OBS with the constructed algorithm as an adjunctive tool to the endoscopist's assessment during endoscopic BE surveillance was demonstrated. These results should be validated in future studies. In addition, other probe‐based spectroscopy techniques may be integrated in this optical biopsy forceps system.     

Barrett's oesophagus: new diagnostic and therapeutic techniques

BACKGROUND: Barrett's oesophagus is associated with an increased risk of developing adenocarcinoma. Cancer development is preceded by dysplastic changes. Yet, detection of these microscopic changes has remained beyond the reach of routine endoscopy. Endoscopic screening in Barrett's therefore relies mainly on extensive random biopsy sampling. METHODS: Update on new endoscopic diagnostics techniques for Barrett's oesophagus. RESULTS: Application of new optical techniques has the potential to enhance our ability to detect dysplasia during endoscopic procedures and take targeted biopsies. Spectral information can be obtained either by point measurements using an optical fibre ('spectral biopsy') or by imaging a broad tissue field. Light-induced fluorescence techniques are based on the observation that tissue when excited by light of shorter wavelength will emit fluorescent light of a longer wavelength. This concept can be used to image tissue in vivo, based on minimal biochemical and structural changes of the (sub)mucosa. Elastic scattering spectroscopy is a spectral biopsy technique that can be exploited even to detect low-grade dysplasia, based on structural information of the mucosa, in which the size and crowding of nuclei in the epithelial layer play a key role. Optical coherence tomography uses reflection of light at optically scattering structures for cross-sectional tissue imaging. Compared to B-scan ultrasonography, optical coherence tomography offers a much higher resolution (10-20 micron), without the need for tissue contact or acoustic coupling. These spectral techniques, although still in their infancy, have already shown the ability to detect early cancer, high-grade dysplasia and in some cases even low-grade dysplasia with a promising degree of sensitivity. As the instruments and the techniques will be further refined, they are likely to become an important part of endoscopic screening. Advances in endoscopic treatment techniques make early malignancies, for which surgical resection is the only accepted therapy, amenable for minimally invasive endoscopic treatment. Endoscopic mucosal resection is a minimally invasive endoscopic technique that can be used in patients with circumscribed mucosal carcinomas. The technique is also useful as a diagnostic procedure by obtaining a full-thickness mucosal specimen for histologic examination. Photodynamic therapy using the prodrug 5-aminolevulinic acid is an ablative therapy that destroys the oesophageal mucosa, leaving the deeper layers of the oesophageal wall intact. Cell damage is achieved by the action of light on the photosensitizing agent protoporphyrin IX in the mucosa, with skin photosensitivity of less than 48 h. Such mucosal ablation, however, can also be accomplished with more common thermal techniques like argon plasma coagulation. In all these ablative procedures, squamous regeneration is obtained by rigorous antacid therapy. In selected patients, these endoscopic ablation methods, although still experimental, might already offer an alternative to oesophagectomy. The need for further improvement, in conjunction with the lack of long-term follow-up data, however, limits the use of these techniques to expert centres. CONCLUSION: New endoscopic techniques are likely to change the diagnostic and therapeutic procedures for Barrett's oesophagus in the near future.     

Endoscopic fluorescence spectroscopy in the upper GI tract for the detection of GI cancer: initial experience

OBJECTIVE: The aim of this study was to investigate autofluorescence spectroscopy using violet-blue excitation light for the in vivo diagnosis of GI cancer during routine endoscopy. METHODS: Fluorescence spectra were obtained from normal mucosa and cancerous lesions of the esophagus and stomach. The spectroscopic system used comprised a special light source capable of delivering either white or violet-blue light to induce autofluorescence of tissue via the endoscope. Endogenous fluorescence spectra emitted by the tissue were recorded with a fiberoptic probe and analyzed with a spectrographic detector system consisting of a polychromator with a photodiode array and an optical multichannel analyzer. The data of each spectrum were sampled within the range of 450-700 nm and stored in a personal computer. RESULTS: Esophageal squamous cell cancer, adenocarcinoma of the esophagus, and adenocarcinoma of the stomach show specific differences in the emitted fluorescence spectra compared with normal mucosa. CONCLUSIONS: Light-induced fluorescence spectroscopy might be a useful tool for the endoscopic in vivo detection of dysplasia and early carcinoma in the upper GI tract. Further trials are needed to test the validity of this new optical detection system.     

Narrow-band imaging with magnifying endoscopy for the evaluation of gastrointestinal lesions

Narrow band imaging(NBI) endoscopy is an optical image enhancing technology that allows a detailed inspection of vascular and mucosal patterns, providing the ability to predict histology during real-time endoscopy. By combining NBI with magnification endoscopy(NBI-ME), the accurate assessment of lesions in the gastrointestinal tract can be achieved, as well as the early detection of neoplasia by emphasizing neovascularization. Promising results of the method in the diagnosis of premalignant and malignant lesions of gastrointestinal tract have been reported in clinical studies. The usefulness of NBI-ME as an adjunct to endoscopic therapy in clinical practice, the potential to improve diagnostic accuracy, surveillance strategies and cost-saving strategies based on this method are summarized in this review. Various classification systems of mucosal and vascular patterns used to differentiate preneoplastic and neoplastic lesions have been reviewed. We concluded that the clinical applicability of NBI-ME has increased, but standardization of endoscopic criteria and classification systems, validation in randomized multicenter trials and training programs to improve the diagnostic performance are all needed before the widespread acceptance of the method in routine practice. However, published data regarding the usefulness of NBI endoscopy are relevant in order to recommend the method as a reliable tool in diagnostic and therapy, even for less experienced endoscopists.     

Screening and surveillance of Barrett esophagus with confocal endomicroscopy and volumetric laser endoscopy

Barrett esophagus (BE) is a premalignant condition that progresses to esophageal adenocarcinoma through an intermediate stage known as dysplasia. Current guidelines recommend that individuals with BE undergo periodic endoscopic surveillance with white light endoscopy and random, 4-quadrant biopsies to identify and treat dysplasia. However, this surveillance strategy is limited by random sampling error and low sensitivity. Surveillance with random biopsies can miss up to 43%-57% of early neoplasia. This review will discuss the current role of 2 advanced imaging techniques, ie, confocal laser endomicroscopy (CLE) and volumetric laser endoscopy (VLE) in screening and surveillance for BE. CLE has the highest accuracy of any endoscopic technique and increases the diagnostic yield and sensitivity for dysplasia and intramucosal neoplasia and reduces the need for unnecessary biopsies. However, CLE is capable of imaging only a small field of mucosa and needs to be incorporated with other advanced imaging techniques to identify suspicious areas that need endomicroscopic evaluation. CLE can be used for the endoscopic evaluation of BE and for the accurate estimation of lesions’ extent and lateral margins to guide endoscopic treatment. CLE is not helpful in assessing the depth of invasion of early neoplastic lesions or in endoscopic surveillance after ablative or resective therapy. VLE is a new imaging modality with limited studies. However, early experience suggests that VLE appears to be a valuable imaging modality in its ability to identify subsquamous BE and buried Barrett glands after mucosal ablation. Overall, CLE and VLE have not been adopted widely due to limited availability, high cost, and need for specific operator training. The major limitation of all studies assessing the role of CLE and VLE in screening and surveillance for BE is that they were all performed by expert endoscopists in tertiary referral centers with a population enriched regarding the proportion of patients with dysplasia. Despite developments in advanced imaging techniques, these techniques are not included in standard surveillance guidelines, and white light endoscopy with random biopsies remains the gold standard for BE surveillance.     

The recognition and endoscopic treatment of early gastric and colonic cancer

As the prognosis of both gastric and colonic cancer remains poor, the challenge is to detect lesions at an early and treatable stage. The benefit of early detection is not only improved survival, but also that patients may be treated with endoscopic mucosal resection, a low-cost, low-morbidity and low-mortality alternative to surgery. In spite of the increasing use of endoscopy in the West, we are not detecting as many early cancers as in Japan. This chapter will discuss the possible reasons for this discrepancy and give a practical guide to 'Japanese endoscopy techniques'. Finally, we have compiled a comprehensive review of the indications, techniques and complications of endoscopic mucosal resection. Throughout the chapter, controversies have been highlighted to give an insight into the limits of our knowledge and stimulate future research.     

Fluorescence and autofluorescence.

Fluorescence detection is one of a series of new spectroscopic techniques currently developed for implementation in endoscopy. This technology is likely to significantly enhance our ability to detect minute lesions and to predict the histology of certain macroscopic lesions. The two fundamental approaches to the fluorescence detection of dysplasia and early malignancy are to use tissue-specific endogenous (auto)fluorescence, and to furnish exogenous fluorophores that accumulate preferentially in neoplastic tissue. Tissue fluorescence can be detected by optical sampling of the mucosa using fluorescence spectroscopy or by taking the fluorescence information into an endoscopic image. The latter technique enables the rapid screening of large surface areas of mucosa. The clinical application of fluorescence detection in dysplasia and early cancer is still in its infancy, yet preliminary data already indicate that fluorescence imaging can indeed provide the endoscopist with real-time, accurate, non-invasive detection of dysplasia and early cancer. Furthermore, the feasibility to surpass the naked eye by detecting dysplastic lesions occult to standard endoscopy has already been established.     

Chromoendoscopy

Accurate detection of premalignant lesions and early cancers in the gastrointestinal tract is essential for curative endoscopic or surgical therapy, because prognosis of the affected patients is closely related to the size and stage of the neoplastic lesion. Recently, it has emerged new endoscopic devices that allow even cellular images in vivo during an endoscopic procedure. These technologies will change and improve endoscopic diagnosis. The combination and integration of different technologies in a multifunctional endoscope will offer new optical features in GI endoscopy. Cytoendoscopy will characterize the surface architecture, confocal laser endomicroscopy will immediately clarify the nature of the lesions by in vivo histology of the mucosal layer, and optical coherence tomography will accurately grade the invasion depth. It will need some additional time before this scenario comes true. Endoscopy will become more complex due to the new visible details. Education and training will play an important future role in GI endoscopy. However, it is not possible to use these novel technologies without before learn to identify early GI cancers lesions. Meanwhile these technologies are perfectionated and we overcome the learning curve to identify early GI lesions, chromoendoscopy will continue to be a safe, easy and inexpensive method.     

DIAGNOSIS OF BARRETT’S ESOPHAGUS AND ESOPHAGEAL NEOPLASIA: EAST MEETS WEST

Barrett’s esophagus has traditionally been considered to be a predominantly ‘Western world’ neoplastic condition. However, over the years, Asian countries are beginning to diagnose increasing numbers of patients with gastroesophageal reflux disease, columnar metaplasia at the gastroesophageal junction, Barrett’s esophagus, and esophageal adenocarcinoma. Hence, the controversies regarding screening for and surveillance of Barrett’s esophagus and esophageal adenocarcinoma have become more widely relevant to gastroenterologists around the world. Emerging concepts related to esophageal cancer prevention and early detection include the screening for Barrett’s esophagus using wireless videocapsule endoscopy, and chromoendoscopy, enhanced high resolution endoscopy. There is also interest in improving surveillance for esophageal neoplasia using novel imaging techniques, such as high resolution and high magnification endoscopy, narrow‐band imaging, autofluorescence imaging, and endocytoscopy/endomicroscopy. The enhanced detection of Barrett’s esophagus and esophageal neoplasia become even more clinically relevant because of accumulating data on the safety and effectiveness of mucosal ablative techniques (such as photodynamic therapy, argon plasma coagulation, low pressure cryotherapy) and endoscopic mucosal resection. This article summarizes the latest developments related to Barrett’s esophagus that are of interest to endoscopists from the East or West.     

Magnifying endoscopy in upper gastroenterology for assessing lesions before completing endoscopic removal

Any prognosis of gastrointestinal (GI) cancer is closely related to the stage of the disease at diagnosis. Endoscopic submucosal dissection (ESD) and en bloc endoscopic mucosal resection (EMR) have been performed as curative treatments for many early-stage GI lesions in recent years. The technologies have been widely accepted in many Asian countries because they are minimally invasive and supply thorough histopathologic evaluation of the specimens. However, before engaging in endoscopic therapy, an accurate diagnosis is a precondition to effecting the complete cure of the underlying malignancy or carcinoma in situ. For the past few years, many new types of endoscopic techniques, including magnifying endoscopy with narrow-band imaging (ME-NBI), have emerged in many countries because these methods provide a strong indication of early lesions and are very useful in determining treatment options before ESD or EMR. However, to date, there is no comparable classification equivalent to "Kudo's Pit Pattern Classification in the colon", for the upper GI, there is still no clear internationally accepted classification system of magnifying endoscopy. Therefore, in order to help unify some viewpoints, here we will review the defining optical imaging characteristics and the current representative classifications of microvascular and microsurface patterns in the upper GI tract under ME-NBI, describe the accurate relationship between them and the pathological diagnosis, and their clinical applications prior to ESD or en bloc EMR. We will also discuss assessing the differentiation and depth of invasion, defying the lateral spread of involvement and targeting biopsy in real time.     

Differences in endoscopic views during biopsy through the right and left lower biopsy channels of the upper gastrointestinal endoscope

Background: It has not been established as to which side the biopsy (instrument) channel should be placed in the tip of a front‐viewing upper gastrointestinal (GI) endoscope to allow an en‐face approach to lesions on various aspects of the stomach wall. Methods: Using a front‐viewing two‐channel endoscope, we identi?ed a difference in endoscopic views during biopsy between lower‐right and lower‐left channels. Colored marks were distributed on the lesser curvature (LC), greater curvature (GC), anterior wall (AW), and posterior wall (PW) in the ‘stomach’ of a dummy for mock‐performance of upper GI endoscopy. When biopsy forceps through the different channels touched the marks, an endoscopic photograph was taken. Furthermore, when biopsy specimens were obtained from PW lesions in several patients, endoscopic views were compared between the two biopsy channels. Results: In the dummy study, no remarkable difference was detected in targeting the marks on AW, LC, or GC of the stomach. The dummy and the patient study showed that the lower‐right approach could target PW lesions with a more adequate endoscopic view than from the lower left. The lower‐left approach targeted PW lesions on the higher body with a nearly blinded endoscopic view. Specimens from PW of the upper body, which could be precisely obtained under direct visual control through the lower‐right channel, were no smaller than those obtained using the channel on the lower left. Conclusion: The present study suggests that the lower‐right channel may be preferable to the lower‐left channel in the tip of a front‐viewing upper GI endoscope.     

Endoscopic photodynamic diagnosis: oral aminolevulinic acid is a marker of GI cancer and dysplastic lesions.

BACKGROUND: Dysplasia and early cancer of the upper gastrointestinal (GI) tract often are undetected at white-light endoscopy. We describe oral administration of 5-aminolevulinic acid for the in vivo photodynamic diagnosis of premalignant and malignant lesions during endoscopy. METHODS: Four patients with known gastric adenoma (n = 1), macroscopically undetected but histologically proven esophageal squamous cell cancer (n = 1), suspected early cancer of the esophagus (n = 1), and multiple duodenal adenomas (n = 1) were sensitized with 5-aminolevulinic acid administered orally (15 mg/kg body weight). Photodynamic diagnosis was conducted after a retention time of 6 to 7 hours with a special light source capable of delivering either white or violet-blue light. Red fluorescence was detected through the gastroscope with an image-intensifying camera. RESULTS: All malignant lesions exhibited red or bluish fluorescence during photodynamic diagnosis. Fluorescence-negative mucosal areas proved to be histologically benign. CONCLUSION: Fluorescence induced with 5-aminolevulinic acid might be useful for the endoscopic detection of dysplasia and early carcinoma in the upper GI tract. Further investigations are needed to evaluate the sensitivity and specificity of photodynamic diagnosis for different tumor entities.     

Early diagnosis of esophageal adenocarcinoma

The incidence of esophageal adenocarcinoma has increased dramatically in developed countries during the past 2 decades, and prognosis remains very poor. Gastroesophageal reflux disease is an important risk factor for this cancer that develops in patients with specialized esophageal metaplasia (Barrett's esophagus). Careful periodic endoscopic examinations, with random biopsy sampling of the entire mucosal surface, are usually recommended for the surveillance of these patients. Several innovative techniques have recently been developed to improve the accuracy of diagnosis of intestinal metaplasia, dysplasia, and early adenocarcinoma in Barrett's esophagus. Some of these techniques (eg, chromoendoscopy, magnifying endoscopy, and light-induced fluorescence endoscopy) are intended to identify suspicious areas of the mucosa not visible during conventional endoscopic examination and to perform targeted biopsies toward these areas to avoid sampling errors. Optical coherence tomography and confocal laser scanning microscopy are other powerful techniques that provide real-time cross-sectional tissue images at a resolution close to that of histology. They allow tissue characterization based solely on optical properties and are likely to replace excisional biopsies. Although promising, none of these techniques is currently recommendable for routine surveillance of patients with Barrett's esophagus. Further evaluation is warranted to define the optimal method and standardize the procedures.     

Diagnosis of Helicobacter pylori‐related chronic gastritis,gastric adenoma and early gastric cancer by magnifying endoscopy

Evaluating the prevalence and severity of gastritis by endoscopy is useful for estimating the risk of gastric cancer (GC). Moreover, understanding the endoscopic appearances of gastritis is important for diagnosing GC due to the fact that superficial mucosal lesions mimicing gastritis (gastritis‐like lesions) are quite difficult to be detected even with optimum preparation and the best technique, and in such cases tissue biopsy is often not very accurate for the diagnosis of gastric epithelial neoplasia. Magnifying endoscopy is a highly accurate technique for the detection of early gastric cancer (EGC). Recent reports have described that various novel endoscopic markers which, visualized by magnifying endoscopy with image‐enhanced system (ME‐IEE), can predict specific histopathological findings. Using ME‐IEE with vessels and surface classification system (VSCS) may represent an excellent diagnostic performance with high confidence and good reproducibility to the endoscopists if performed under consistent conditions, including observation under maximal magnification. The aim of this review was to discuss how to identify high‐risk groups for GC by endoscopy, and how to detect effectively signs of suspicious lesions by conventional white light imaging (C‐WLI) or chromoendoscopy (CE). Furthermore, to characterize suspicious lesions using ME‐IEE using the criteria and classification of EGC based upon VSCS.