From the surface to the single cell: Novel endoscopic approaches in inflammatory bowel disease

Inflammatory bowel diseases(IBD) comprise the two major entities Crohn's disease and ulcerative colitis and endoscopic imaging of the gastrointestinal tract has always been an integral and central part in the management of IBD patients. Within the recent years,mucosal healing emerged as a key treatment goal in IBD that substantially decides about the clinical outcome of IBD patients,thereby demanding for a precise,timely and detailed endoscopic assessment of the mucosal inflammation associated with IBD. Further,molecular imaging has tremendously expanded the clinical utility and applications of modern endoscopy,now encompassing not only diagnosis,surveillance,and treatment but also the prediction of individual therapy response. Within this review we describe novel endoscopic approaches and advanced endoscopic imaging methods for the diagnosis,treatment and surveillance of IBD patients. We begin by providing an overview over novel and advanced imaging techniques such as magnification endoscopy and dye-based and dye-less chromoendoscopy,endomicroscopy and endocytoscopy. We then describe how these techniques can be utilized for the precise and ultrastructural assessment of mucosal inflammation and dysplasia development associated with IBD and outline how they have enabled the endoscopist to gain insight onto the cellular level in real-time. Finally,we provide an outlook on how molecular imaging has rapidly evolved in the recent past and can be used to make individual predictions about the therapeutic response towards biological treatment.     

The role of endoscopy in early postoperative haemorrhage

Diagnostic as well as therapeutic endoscopy has a decisive role in management of early postoperative haemorrhage. Endoscopy combines easy access to the upper and lower gastrointestinal tract and application of an array of interventional tools. In near future, even the small bowel will be accessible for diagnostic and therapeutic measures due to the advent of double-balloon enteroscopy. Thus, the endoscopist increasingly replaces the surgeon for diagnosis and therapy of postsurgical bleeding. Published data on frequency and aetiology of postoperative haemorrhage are scarce and mainly casuistic. Sources of gastrointestinal bleeding associated with surgery may be: anastomotic ulcers, mucosal ischaemia, 'stress' ulcers, reflux-induced lesions, coagulopathies (e.g. in sepsis or after organ transplantation) and aortoenteric fistula after bypass surgery. The endoscopist will frequently identify the culprit lesion and guide further management of the patient (e.g. endoscopic approach, repeated surgery, interventional radiology). All accessible lesions in postoperative haemorrhage should primarily be treated by endoscopic means, except aortoenteric fistulas. There is even a place for repeated endoscopy in recurrent bleeding. In the face of lacking controlled data, the endoscopist often has to rely on his personal experience in the selection of therapeutic options.     

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.     

Photodiagnostic techniques for the endoscopic detection of premalignant gastrointestinal lesions

Considerable attention is given to the clinical diagnosis of gastrointestinal (GI) malignancies as they remain the second leading cause of cancer‐associated deaths in developed countries. Detection and intervention at an early stage of preneoplastic development significantly improve patient survival. High‐risk assessment of asymptomatic patients is currently performed by strict endoscopic surveillance biopsy protocols aimed at early detection of dysplasia and malignancy. However, poor sensitivity associated with frequent surveillance programs incorporating conventional screening tools, such as white light endoscopy and multiple random biopsy, is a significant limitation. Recent advances in biomedical optics are illuminating new ways to detect premalignant lesions of the GI tract with endoscopy. The present review presents a summary report on the newest developments in modern GI endoscopy, which are based on novel optical endoscopic techniques: fluorescence endoscopic imaging and spectroscopy, Raman spectroscopy, light scattering spectroscopy, optical coherence tomography, chromoendoscopy, confocal fluorescence endoscopy and immunofluorescence endoscopy. Relying on the interaction of light with tissue, these ‘state‐of‐the‐art’ techniques potentially offer an improved strategy for diagnosis of early mucosal lesions by facilitating targeted excisional biopsies. Furthermore, the prospects of real‐time ‘optical biopsy’ and improved staging of lesions may significantly enhance the endoscopist's ability to detect subtle preneoplastic mucosal changes and lead to curative endoscopic ablation of these lesions. Such advancements within this specialty will be rewarded in the long term with improved patient survival and quality of life.     

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.     

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.     

Technology insight: endoscopic submucosal dissection of gastrointestinal neoplasms

Gastrointestinal neoplasms can be cured by local resection as long as the lesions are in the early stage and have not metastasized. Endoscopic resection is a minimally invasive treatment for early-stage gastrointestinal neoplasms, and endoscopic submucosal dissection (ESD) is one type of endoscopic resection that has been developed in the past 10 years. For ESD to be a reliable, curative treatment for gastrointestinal neoplasms, it is necessary for the endoscopist to detect the lesion early, make a precise pretreatment diagnosis, ensure that the patient has the correct indication for endoscopic resection, and have the skill to perform ESD. For early lesion detection, endoscopists should pay attention to subtle changes in the surface structure, the color of the mucosa and the visibility of underlying submucosal vessels. Chromoendoscopy and magnifying endoscopy are useful for determining the margin of the lesions for pretreatment diagnosis, and endoscopic ultrasonography and magnifying endoscopy are useful for determining the depth of invasion. For ESD to be successful, local injection of sodium hyaluronate helps maintain mucosal elevation during dissection. Selecting the appropriate knife, using transparent hoods wisely, employing a good strategy that uses gravity, and having good control of bleeding are all needed to make ESD reliable.     

Advances in endoscopic imaging in ulcerative colitis

Modern strategies for the treatment of ulcerative colitis require more accurate tools for gastrointestinal imaging to better assess mucosal disease activity and long-term prognostic clinical outcomes. Recent advances in gastrointestinal luminal endoscopy are radically changing the role of endoscopy in every-day clinical practice and research trials. Advanced endoscopic imaging techniques including high-definition endoscopes, optical magnification endoscopy, and various chromoendoscopy techniques have remarkably improved endoscopic assessment of ulcerative colitis. More recently, optical biopsy techniques with either endocytoscopy or confocal laser endomicroscopy have shown great potential in predicting several histological changes in real time during ongoing endoscopy. Here, we review current applications of advanced endoscopic imaging techniques in ulcerative colitis and present the most promising upcoming headways in this field.     

Endoscopic detection of early lower gastrointestinal cancer

The prognosis for patients with malignancies of the lower gastrointestinal tract is strictly dependent on early detection of premalignant and malignant lesions. What should an ideal screening and surveillance colonoscopy be able to accomplish? The technique should allow detection of large but also discrete mucosal alterations. Ideally, endoscopic discrimination between neoplastic and non-neoplastic lesions would be possible during the ongoing procedure. At present, endoscopy can be performed with powerful new endoscopes. Comparable to the rapid development in chip technology, the optical features of the newly designed endoscopes offer resolutions, which allow new surface details to be seen. In conjunction with chromoendoscopy, the newly discovered tool video colonoscopy is much easier and more impressive today than with the previously used fibre-optic endoscopes. Recently, new endoscopic technologies such as narrow band imaging, endocytoscopy, or confocal laser endoscopy have allowed the discovery of a whole new world of image details which will surely improve the diagnostic yield in the field of early malignancies. This review summarises newly available technologies and clinical data about the diagnosis of early lower gastrointestinal cancers.     

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.     

Advanced endoscopic imaging methods for colon neoplasia

The main goal of lumenal endoscopic visualization of the colon is to detect mucosal pathologies, which when removed will result in cure or palliation of a disease process. Whereas traditionally endoscopic imaging was performed with fiber-optic technology, currently there are many new methods that improve our visual acuity when evaluating the colon mucosa. Most of these methods are collectively called 'advanced colonic imaging'. The 2 main aims of standard (white light) and advanced colonic imaging are to enhance the superficial mucosal detail (i.e. 'pit pattern') and allow a detailed view of the submucosal capillary pattern, thus potentially improving the detection characterization of pathological lesions. However, the current literature dealing with most methods used for advanced endoscopic imaging of the colon is fraught with many controversial findings which have resulted in opposing views regarding its utility. Whereas some investigators vehemently support the use of most of these methods in routine clinical practice, most experts and practicing endoscopists still refuse to accept that these methods aid in the clinical routine. For now, white light video-colonoscopy and high-definition white light video-colonoscopy will remain the standard endoscopic methods for investigating the colon mucosa until new methods convincingly and clearly prove their superiority over white light endoscopy.     

Efforts to increase image quality during endoscopy:The role of pronase

Clear visualization of the gastrointestinal mucosal surface is essential for thorough endoscopy. An unobstructed assessment can reduce the need for additional timeconsuming manipulations such as frequent washing and suction,which tend to prolong total procedure time. However,mucus,foam,and bubbles often hinder clear visibility during endoscopy. Premedication with pronase,a compound of mixed proteolytic enzymes,has been studied in order to improve mucosal visibility during endoscopy. Although its effects differ according to the location in the stomach,premedication with pronase 10 to 20 min before endoscopy significantly improves mucosal visibility without affecting the accuracy of Helicobacter pylori identification. The effects of pronase as premedication also extend to chromoendoscopy,narrow-band imaging,magnifying endoscopy,and endoscopic ultrasonography. In addition,endoscopic flushing with pronase during endoscopy may improve the quantity and the quality of a biopsy to some degree. Although improved mucosal visibility does not necessarily improve clinical outcomes,premedication with pronase may be helpful for increasing the detection rate of early cancers.     

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.     

Novel imaging modalities in the detection of oesophageal neoplasia

The prognosis of oesophageal neoplasia is dependent on the stage of the disease at the time of detection. Early lesions have an excellent prognosis in contrast to more advanced stages that usually have a dismal prognosis. Therefore, the early detection of these lesions is of the utmost importance. In recent years, several new techniques have been introduced to improve the endoscopic detection of early lesions. The most important improvement, in general, has been the introduction of high-resolution/high-definition endoscopy into daily clinical practice. The value of superimposing techniques such as chromoendoscopy, narrow band imaging and computed virtual chromoendoscopy onto high-resolution/high-definition endoscopy will have to be proven in randomised cross-over trials comparing these techniques with standard techniques. Important future adjuncts to white-light endoscopy serving as 'red-flag' techniques for the detection of early neoplasia may be broad field functional imaging techniques such as video autofluorescence endoscopy. In addition, real-time histopathology during endoscopy has become possible with endocytoscopy and confocal endomicroscopy. The clinical value of these techniques needs to be ascertained in the coming years.     

回盲部病变诊断的研究进展

回盲部包括回盲瓣、回肠末段、盲肠、阑尾及升结肠始段,该部位可受到来自消化系及其以外的各种致病因素的影响,是多种肠道疾病的好发部位,鉴别诊断困难,其诊断需病史、临床特征、影像学及内镜病检的综合支持.随着各种新的影像及内镜技术的发展,回盲部疾病的检出率在不断提高.本文将综合对回盲部病变的内镜及影像学检查及相应的优势及劣势进行综述,为临床医师在诊治该部位病变时提供参考.     

Reasons for False Negatives in the Endoscopic Screening for Cancer in the Upper Gastrointestinal Tract

Abstract: The following paper is a study of 119 gastric cancer lesions that were not diagnosed as malignant in the first gastroscopic examination. These cases were classified according to their endoscopic appearance, and the frequency with which they appeared was compared with the frequency of that type of lesion in the population that receives endoscopy. Gastric ulceration, adenomas, polyps, submucosal tumors, acute gastric mucosal lesions, and gastric redness appeared more frequently in the false negative group than in the population that receives endoscopy. Atrophic gastritis, duodenal ulceration, gastric ulcer scar and gastric erosion appeared less frequently in this group titan in the population that receives endoscopy. To evaluate whether malignancy should really have been suspected in the lesions, the gastroscopic pictures were reviewed by an expert endoscopist. In only 15% of the lesions was cancer not suspected by the expert endoscopist. Chromoscopy as an auxiliary method for the endoscopist was used in only about half of the cases. Depending on the experience of the endoscopist, some endoscopic findings appeared more often than others: i- INTERMEDIATE and BEGINNING endoscopists mainly mistook cancer for gastric ulceration. ii-EXPERT endoscopists confused many more adenomas and polips. We conclude that some gastric lesions are more easily confused in regard to malignancy than others, and that the experience level of the endoscopist stakes hint or her more prone to confusing certain kinds of lesions.     

Magnifying endoscopy in upper gastrointestinal tract]

For the diagnosis of upper gastrointestinal (GI) lesions, magnification method is usually used in conjunction with chromoscopy, enabling the endoscopist to view subtle mucosal patterns in exquisite detail. Recently published datas have shown that magnifying endoscopy might be a valuable adjunct for the diagnosis, detection, and characterization of inflammatory and neoplastic lesions of the upper GI tract. It is also proven to be an useful surveillance protocol in identifying dysplastic epithelium or early cancer within a segment of Barrett's esophagus. Possible indications for magnifying endoscopy in upper GI tract include screening and surveillance of Barrett's esophagus, defining the extent of esophageal and gastric adenocarcinoma, detecting synchronous/metachronous gastric and esophageal cancers, diagnosing Helicobacter pylori infection, and recognizing minimal mucosal changes in gastroesophageal reflux disease. By grading the quality of evidence for the currently published trials, it is clear that the majority are case series, case reports, and/or observational studies without randomization, control, or blinding. Moreover, other evidence-based criteria such as independent, blind comparisons of magnifying endoscopy with a standard method which evaluates this technology in an appropriate spectrum of patients to whom the test may be applicable, and standardizing methodology would be crucial before magnifying endoscopy becomes a standard procedure in clinical practice. In the future, a uniform classification system for staining and magnifying patterns should be devised and observer agreement should be tested. Futher studies then could be performed based upon consistent, validated, and standardized terminologies and criteria.     

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.