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1.  Autofluorescence imaging and magnification endoscopy 
It is well known that angiogenesis is critical in the transition from premalignant to malignant lesions. Consequently, early detection and diagnosis based on morphological changes to the microvessels are crucial. In the last few years, new imaging techniques which utilize the properties of light-tissue interaction have been developed to increase early diagnosis of gastrointestinal (GI) tract neoplasia. We analyzed several “red-flag” endoscopic techniques used to enhance visualization of the vascular pattern of preneoplastic and neoplastic lesions (e.g. trimodal imaging including autofluorescence imaging, magnifying endoscopy and narrow band imaging). These new endoscopic techniques provide better visualization of mucosal microsurface structure and microvascular architecture and may enhance the diagnosis and characterization of mucosal lesions in the GI tract. In the near future, it is expected that trimodal imaging endoscopy will be practiced as a standard endoscopy technique as it is quick, safe and accurate for making a precise diagnosis of gastrointestinal pathology, with an emphasis on the diagnosis of early GI tract cancers. Further large-scale randomized controlled trials comparing these modalities in different patient subpopulations are warranted before their endorsement in the routine practice of GI endoscopy.
PMCID: PMC3016686  PMID: 21218078
Angiogenesis; Autofluorescence imaging; Multiband imaging; Narrow band imaging; Zoom endoscopy
2.  Molecular Imaging in Gastrointestinal Endoscopy 
Gastroenterology  2010;138(3):828-33.e1.
Molecular imaging is a rapidly growing new discipline in gastrointestinal endoscopy. It uses the molecular signature of cells for minimally-invasive, targeted imaging of gastrointestinal pathologies. Molecular imaging comprises wide field techniques for the detection of lesions and microscopic techniques for in vivo characterization. Exogenous fluorescent agents serve as molecular beacons and include labeled peptides and antibodies, and probes with tumor-specific activation. Most applications have aimed at improving the detection of gastrointestinal neoplasia with either prototype fluorescence endoscopy or confocal endomicroscopy, and first studies have translated encouraging results from rodent and tissue models to endoscopy in humans. Even with the limitations of the currently used approaches, molecular imaging has the potential to greatly impact on future endoscopy in gastroenterology.
PMCID: PMC3335170  PMID: 20096697
Molecular imaging; endoscopy; confocal endomicroscopy; autofluorescence imaging; cancer; EGFR
3.  State of the art in advanced endoscopic imaging for the detection and evaluation of dysplasia and early cancer of the gastrointestinal tract 
Ideally, endoscopists should be able to detect, characterize, and confirm the nature of a lesion at the bedside, minimizing uncertainties and targeting biopsies and resections only where necessary. However, under conventional white-light inspection – at present, the sole established technique available to most of humanity – premalignant conditions and early cancers can frequently escape detection. In recent years, a range of innovative techniques have entered the endoscopic arena due to their ability to enhance the contrast of diseased tissue regions beyond what is inherently possible with standard white-light endoscopy equipment. The aim of this review is to provide an overview of the state-of-the-art advanced endoscopic imaging techniques available for clinical use that are impacting the way precancerous and neoplastic lesions of the gastrointestinal tract are currently detected and characterized at endoscopy. The basic instrumentation and the physics behind each method, followed by the most influential clinical experience, are described. High-definition endoscopy, with or without optical magnification, has contributed to higher detection rates compared with white-light endoscopy alone and has now replaced ordinary equipment in daily practice. Contrast-enhancement techniques, whether dye-based or computed, have been combined with white-light endoscopy to further improve its accuracy, but histology is still required to clarify the diagnosis. Optical microscopy techniques such as confocal laser endomicroscopy and endocytoscopy enable in vivo histology during endoscopy; however, although of invaluable assistance for tissue characterization, they have not yet made transition between research and clinical use. It is still unknown which approach or combination of techniques offers the best potential. The optimal method will entail the ability to survey wide areas of tissue in concert with the ability to obtain the degree of detailed information provided by microscopic techniques. In this respect, the challenging combination of autofluorescence imaging and confocal endomicroscopy seems promising, and further research is awaited.
Video abstract
PMCID: PMC4028486  PMID: 24868168
image-enhanced endoscopy; narrowband imaging; autofluorescence imaging; confocal laser endomicroscopy; fluorescence lifetime imaging
4.  Screening for Precancerous Lesions of Upper Gastrointestinal Tract: From the Endoscopists' Viewpoint 
Upper gastrointestinal tract cancers are one of the most important leading causes of cancer death worldwide. Diagnosis at late stages always brings about poor outcome of these malignancies. The early detection of precancerous or early cancerous lesions of gastrointestinal tract is therefore of utmost importance to improve the overall outcome and maintain a good quality of life of patients. The desire of endoscopists to visualize the invisibles under conventional white-light endoscopy has accelerated the advancements in endoscopy technologies. Nowadays, image-enhanced endoscopy which utilizes optical- or dye-based contrasting techniques has been widely applied in endoscopic screening program of gastrointestinal tract malignancies. These contrasting endoscopic technologies not only improve the visualization of early foci missed by conventional endoscopy, but also gain the insight of histopathology and tumor invasiveness, that is so-called optical biopsy. Here, we will review the application of advanced endoscopy technique in screening program of upper gastrointestinal tract cancers.
PMCID: PMC3615623  PMID: 23573079
5.  Endoscopy in screening for digestive cancer 
The aim of this study is to describe the role of endoscopy in detection and treatment of neoplastic lesions of the digestive mucosa in asymptomatic persons. Esophageal squamous cell cancer occurs in relation to nutritional deficiency and alcohol or tobacco consumption. Esophageal adenocarcinoma develops in Barrett’s esophagus, and stomach cancer in chronic gastric atrophy with Helicobacter pylori infection. Colorectal cancer is favoured by a high intake in calories, excess weight, low physical activity. In opportunistic or individual screening endoscopy is the primary detection procedure offered to an asymptomatic individual. In organized or mass screening proposed by National Health Authorities to a population, endoscopy is performed only in persons found positive to a filter selection test. The indications of primary upper gastrointestinal endoscopy and colonoscopy in opportunistic screening are increasingly developing over the world. Organized screening trials are proposed in some regions of China at high risk for esophageal cancer; the selection test is cytology of a balloon or sponge scrapping; they are proposed in Japan for stomach cancer with photofluorography as a selection test; and in Europe, America and Japan; for colorectal cancer with the fecal occult blood test as a selection test. Organized screening trials in a country require an evaluation: the benefit of the intervention assessed by its impact on incidence and on the 5 year survival for the concerned tumor site; in addition a number of bias interfering with the evaluation have to be controlled. Drawbacks of screening are in the morbidity of the diagnostic and treatment procedures and in overdetection of none clinically relevant lesions. The strategy of endoscopic screening applies to early cancer and to benign adenomatous precursors of adenocarcinoma. Diagnostic endoscopy is conducted in 2 steps: at first detection of an abnormal area through changes in relief, in color or in the course of superficial capillaries; then characterization of the morphology of the lesion according to the Paris classification and prediction of the risk of malignancy and depth of invasion, with the help of chromoscopy, magnification and image processing with neutrophil bactericidal index or FICE. Then treatment decision offers 3 options according to histologic prediction: abstention, endoscopic resection, surgery. The rigorous quality control of endoscopy will reduce the miss rate of lesions and the occurrence of interval cancer.
PMCID: PMC3536848  PMID: 23293721
Esophagus; Stomach; Colon; Adenoma; Adenocarcinoma; Endoscopy; Screening
6.  Indications, stains and techniques in chromoendoscopy 
Early detection of malignancies within the gastrointestinal tract is essential to improve the prognosis and outcome of affected patients. However, conventional white light endoscopy has a miss rate of up to 25% for gastrointestinal pathology, specifically in the context of small and flat lesions within the colon. Chromoendoscopy and other advanced imaging techniques aim at facilitating the visualization and detection of neoplastic lesions and have been applied throughout the gastrointestinal tract. Chromoendoscopy, particularly in combination with magnifying endoscopy has significantly improved means to detect neoplastic lesions in the gastrointestinal mucosa, particularly in ulcerative colitis and Crohn’s colitis. In addition, chromoendoscopy is beneficial in the upper gastrointestinal tract, especially when evaluating Barrett’s oesophagus (BO) for the presence of dysplasia. Furthermore, it also improves characterization, differentiation and diagnosis of endoscopically detected suspicious lesions, and helps to delineate the extent of neoplastic lesions that may be amenable to endoscopic resection. This review discusses the dyes, indications and advanced endoscopic imaging methods used in various chromoendoscopic techniques, and presents a critical overview of the existing evidence supporting their use in current practice with a particular emphasis on the role in inflammatory bowel disease and BO.
PMCID: PMC3550597  PMID: 23097386
7.  International Digestive Endoscopy Network 2012: A Patchwork of Networks for the Future 
Clinical Endoscopy  2012;45(3):209-210.
This special September issue of Clinical Endoscopy will discuss various aspects of diagnostic and therapeutic advancement of gastrointestinal (GI) endoscopy, explaining what is new in digestive endoscopy and why international network should be organized. We proposed an integrated model of international conference based on the putative occurrence of Digestive Endoscopy Networks. In International Digestive Endoscopy Network (IDEN) 2012, role of endoscopy in gastroesophageal reflux disease and Barrett's esophagus, endoscopy beyond submucosa, endoscopic treatment for stricture and leakage in upper GI, how to estimate the invasion depth of early GI cancers, colonoscopy in inflammatory bowel disease (IBD), a look into the bowel beyond colon in IBD, management of complications in therapeutic colonoscopy, revival of endoscopic papllirary balloon dilation, evaluation and tissue acquisition for indeterminate biliopancreatic stricture, updates in the evaluation of pancreatic cystic lesions, issues for tailored endoscopic submucosal dissection (ESD), endoluminal stents, management of upper GI bleeding, endoscopic management of frustrating situations, small bowel exploration, colorectal ESD, valuable tips for frustrating situations in colonoscopy, choosing the right stents for endoscopic stenting of biliary strictures, advanced techniques for pancreaticobiliary visualization, endoscopic ultrasound-guided biliopancreatic drainage, and how we can overcome the obstacles were deeply touched. We hope that IDEN 2012, as the very prestigious endoscopy networks, served as an opportunity to gain some clues for further understanding of endoscopic technologies and to enhance up-and-coming knowledge and their clinical implications from selected 25 peer reviewed articles and 112 invited lectures.
PMCID: PMC3429737  PMID: 22977803
IDEN; Network; Digestive endoscopy
Over the past two decades, the bulk of gastrointestinal (GI) endoscopic procedures has shifted away from diagnostic and therapeutic interventions for symptomatic disease toward cancer prevention in asymptomatic patients. This shift has resulted largely from a decrease in the incidence of peptic ulcer disease in the era of antisecretory medications coupled with emerging evidence for the efficacy of endoscopic detection and eradication of dysplasia, a histopathological biomarker widely accepted as a precursor to cancer. This shift has been accompanied by a drive toward minimally-invasive, in situ optical diagnostic technologies that help assess the mucosa for cellular changes that relate to dysplasia. Two competing but complementary approaches have been pursued. The first approach is based on broad-view targeting of “areas of interest” or “red flags.” These broad-view technologies include standard white light endoscopy (WLE), high-definition endoscopy (HD), and “electronic” chromoendoscopy (narrow-band-type imaging). The second approach is based on multiple small area or point-source (meso/micro) measurements, which can be either machine (spectroscopy) or human-interpreted (endomicroscopy, magnification endoscopy), much as histopatholgy slides are. In this paper we present our experience with the development and testing of a set of familiar but “smarter” standard tissue-sampling tools that can be routinely employed during screening/surveillance endoscopy. These tools have been designed to incorporate fiberoptic probes that can mediate spectroscopy or endomicroscopy. We demonstrate the value of such tools by assessing their preliminary performance from several ongoing clinical studies. Our results have shown promise for a new generation of integrated optical tools for a variety of screening/surveillance applications during GI endoscopy. Integrated devices should prove invaluable for dysplasia surveillance strategies that currently result in large numbers of benign biopsies, which are of little clinical consequence, including screening for colorectal polyps and surveillance of “flat” dysplasia such as Barrett’s esophagus and chronic colitis due to inflammatory bowel diseases.
PMCID: PMC2997708  PMID: 21152112
9.  Functional imaging and endoscopy 
The emergence of endoscopy for the diagnosis of gastrointestinal diseases and the treatment of gastrointestinal diseases has brought great changes. The mere observation of anatomy with the imaging mode using modern endoscopy has played a significant role in this regard. However, increasing numbers of endoscopies have exposed additional deficiencies and defects such as anatomically similar diseases. Endoscopy can be used to examine lesions that are difficult to identify and diagnose. Early disease detection requires that substantive changes in biological function should be observed, but in the absence of marked morphological changes, endoscopic detection and diagnosis are difficult. Disease detection requires not only anatomic but also functional imaging to achieve a comprehensive interpretation and understanding. Therefore, we must ask if endoscopic examination can be integrated with both anatomic imaging and functional imaging. In recent years, as molecular biology and medical imaging technology have further developed, more functional imaging methods have emerged. This paper is a review of the literature related to endoscopic optical imaging methods in the hopes of initiating integration of functional imaging and anatomical imaging to yield a new and more effective type of endoscopy.
PMCID: PMC3214702  PMID: 22090783
Endoscopy; Functional imaging; Multi-modal imaging; Optical coherence tomography; Fluorescence molecular imaging; Photoacoustic tomography; Cerenkov luminescence tomography
10.  Ultra high magnification endoscopy: Is seeing really believing? 
Endoscopy is an indispensible diagnostic and therapeutic instrument for gastrointestinal diseases. Endocytoscopy and confocal endomicroscopy are two types of ultra high magnification endoscopy techniques. Standard endoscopy allows for 50 × magnification, whereas endocytoscopy can magnify up to 1400 × and confocal endomicroscopy can magnify up to 1000 ×. These methods open the realm of real time microscopic evaluation of the GI tract, including cellular and subcellular structures. Confocal endomicroscopy has the additional advantage of being able to visualize subsurface structures. The use of high magnification endoscopy in conjunction with standard endoscopy allows for a real-time microscopic assessment of areas with macroscopic abnormalities, providing “virtual biopsies” with valuable information about cellular and subcellular changes. This can minimize the number of biopsies taken at the time of endoscopy. The use of this technology may assist in detecting pre-malignant or malignant changes at an earlier state, allowing for earlier intervention and treatment. High magnification endoscopy has shown promising results in clinical trials for Barrett’s esophagus, esophageal adenocarcinoma, esophageal squamous cell cancer, gastric cancer, celiac disease, colorectal cancer, and inflammatory bowel disease. As the use of high magnification endoscopy techniques increases, the clinical applications will increase as well. Of the two systems, only confocal endomicroscopy is currently commercially available. Like all new technologies there will be an initial learning curve before operators become proficient in obtaining high quality images and discerning abnormal from normal pathology. Validated criteria for the diagnosis of the various gastrointestinal diseases will need to be developed for each method. In this review, the basic principles of both modalities are discussed, along with their clinical applicability and limitations.
PMCID: PMC3506956  PMID: 23189217
Endocytoscopy; Confocal endomicroscopy; Confocal laser endomicroscopy; High magnification endoscopy
11.  Molecular Imaging for Guiding Oncologic Prognosis and Therapy in Esophageal Adenocarcinoma 
Hospital practice (1995)  2011;39(2):97-106.
In the last 30 years, the incidence of esophageal adenocarcinoma has skyrocketed. Sadly, advances in treatment have not followed the same trend, and the prognosis for patients with esophageal adenocarcinoma remains poor with a 5-year survival rate of only 15%. Like most cancers, early detection is the key to improving prognosis, but this outcome has proven difficult in the esophagus for several reasons: 1) patients present with advanced disease because “alarm symptoms” such as dysphagia occur at a late stage, and 2) high-grade dysplasia (HGD) and early adenocarcinoma (ACA) are not visible on routine surveillance endoscopy. Currently, the recommended surveillance strategy involves collection of random biopsies, an imperfect technique that is limited by sampling error and is infrequently used because of the considerable time and cost it requires. Even in patients with biopsy-proven dysplasia, adequate guidance for clinical management decisions is still lacking. Dysplasia alone is not an entirely reliable biomarker for the risk of progression to adenocarcinoma because the natural history of this condition is extremely variable. Clearly, there is a need for additional biomarkers that can better characterize this disease, and thus improve our ability to treat patients on an individual basis. As we better understand the molecular changes that lead to the development of this cancer, new molecular biomarkers are needed to allow for more personalized diagnoses, surveillance and treatment. Targeted agents against EGFR, HER2/neu and VEGF are currently being evaluated for their role in combination chemotherapy for metastatic esophageal adenocarcinoma. As these studies progress, a reliable approach for determining receptor status in individual patients is essential. Molecular imaging uses fluorescent probes that target specific cell surface receptors, and has the potential to evaluate an individual patient’s gene expression profile. By topically applying fluorescent probes to dysplastic epithelium during endoscopy, a variety of receptors can be visualized, and the response to treatment can be monitored in real time. This technique can mitigate the limitations of current surveillance protocols, allow for improved cancer detection, and be used for truly personalized treatment in the future.
PMCID: PMC3227392  PMID: 21576902
12.  Vital-dye enhanced fluorescence imaging of gastrointestinal mucosa: metaplasia, neoplasia, inflammation 
Gastrointestinal Endoscopy  2012;75(4):877-887.
Confocal endomicroscopy has revolutionized endoscopy by offering sub-cellular images of gastrointestinal epithelium; however, field-of-view is limited. There is a need for multi-scale endoscopy platforms that use widefield imaging to better direct placement of high-resolution probes.
Feasibility Study
This study evaluates the feasibility of a single agent, proflavine hemisulfate, as a contrast medium during both widefield and high resolution imaging to characterize morphologic changes associated with a variety of gastrointestinal conditions.
U.T. M.D. Anderson Cancer Center (Houston, TX) and Mount Sinai Medical Center (New York, NY)
Patients, Interventions, and Main Outcome Measurements
Surgical specimens were obtained from 15 patients undergoing esophagectomy/colectomy. Proflavine, a vital fluorescent dye, was applied topically. Specimens were imaged with a widefield multispectral microscope and a high-resolution microendoscope. Images were compared to histopathology.
Widefield-fluorescence imaging enhanced visualization of morphology, including the presence and spatial distribution of glands, glandular distortion, atrophy and crowding. High-resolution imaging of widefield-abnormal areas revealed that neoplastic progression corresponded to glandular heterogeneity and nuclear crowding in dysplasia, with glandular effacement in carcinoma. These widefield and high-resolution image features correlated well with histopathology.
This imaging approach must be validated in vivo with a larger sample size.
Multi-scale proflavine-enhanced fluorescence imaging can delineate epithelial changes in a variety of gastrointestinal conditions. Distorted glandular features seen with widefield imaging could serve as a critical ‘bridge’ to high-resolution probe placement. An endoscopic platform combining the two modalities with a single vital-dye may facilitate point-of-care decision-making by providing real-time, in vivo diagnoses.
PMCID: PMC3336371  PMID: 22301343
fluorescence imaging; Barrett's esophagus; esophageal adenocarcinoma; colonic adenocarcinoma; inflammatory bowel disease
13.  Modern treatment of gastric gastrointestinal stromal tumors 
Gastrointestinal stromal tumors (GIST) are rare mesenchymal smooth muscle sarcomas that can arise anywhere within the gastrointestinal tract. Sporadic mutations within the tyrosine kinase receptors of the interstitial cells of Cajal have been identified as the key molecular step in GIST carcinogenesis. Although many patients are asymptomatic, the most common associated symptoms include: abdominal pain, dyspepsia, gastric outlet obstruction, and anorexia. Rarely, GIST can perforate causing life-threatening hemoperitoneum. Most are ultimately diagnosed on cross-sectional imaging studies (i.e., computed tomography and/or magnetic resonance imaging in combination with upper endoscopy. Endoscopic ultrasonographic localization of these tumors within the smooth muscle layer and acquisition of neoplastic spindle cells harboring mutations in the c-KIT gene is pathognomonic. Curative treatment requires a complete gross resection of the tumor. Both open and minimally invasive operations have been shown to reduce recurrence rates and improve long-term survival. While there is considerable debate over whether GIST can be benign neoplasms, we believe that all GIST have malignant potential, but vary in their propensity to recur after resection and metastasize to distant organ sites. Prognostic factors include location, size (i.e., > 5 cm), grade (> 5-10 mitoses per 50 high power fields and specific mutational events that are still being defined. Adjuvant therapy with tyrosine kinase inhibitors, such as imatinib mesylate, has been shown to reduce the risk of recurrence after one year of therapy. Treatment of locally-advanced or borderline resectable gastric GIST with neoadjuvant imatinib has been shown to induce regression in a minority of patients and stabilization in the majority of cases. This treatment strategy potentially reduces the need for more extensive surgical resections and increases the number of patients eligible for curative therapy. The modern surgical treatment of gastric GIST combines the novel use of targeted therapy and aggressive minimally invasive surgical procedures to provide effective treatment for this lethal, but rare gastrointestinal malignancy.
PMCID: PMC3520160  PMID: 23239909
Gastrointestinal stromal tumors; Laparoscopic resections of gastrointestinal stromal tumors; Imatinib mesylate; Gastrectomy
14.  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.
PMCID: PMC2169359  PMID: 15354274
15.  Targeted Endoscopic Imaging 
Endoscopy has undergone explosive technological growth in over recent years, and with the emergence of targeted imaging, its truly transformative power and impact in medicine lies just over the horizon. Today, our ability to see inside the digestive tract with medical endoscopy is headed toward exciting crossroads. The existing paradigm of making diagnostic decisions based on observing structural changes and identifying anatomical landmarks may soon be replaced by visualizing functional properties and imaging molecular expression. In this novel approach, the presence of intracellular and cell surface targets unique to disease are identified and used to predict the likelihood of mucosal transformation and response to therapy. This strategy can result in the development of new methods for early cancer detection, personalized therapy, and chemoprevention. This targeted approach will require further development of molecular probes and endoscopic instruments, and will need support from the FDA for streamlined regulatory oversight. Overall, this molecular imaging modality promises to significantly broaden the capabilities of the gastroenterologist by providing a new approach to visualize the mucosa of the digestive tract in a manner that has never been seen before.
PMCID: PMC3217463  PMID: 19423025
endoscopy; molecular imaging; targets; early detection
16.  Clinical Experience Using a Real Time Autofluorescence Endoscopy System in the Gastrointestinal Tract 
Autofluorescence spectra of neoplastic tissues have been reported to be significantly different from those of normal tissues when excited by blue or violet light. From this concept, a light-induced autofluorescence endoscopic imaging system for gastrointestinal mucosa (LIFE-GI; Xillix, Canada and Olympus, Japan) has been newly developed and the clinical evaluation of the prototype system has been conducted in hospitals in Canada, Netherlands and Japan.
We examined the clinical usefulness of the prototype LIFE-GI system for the detection of gastrointestinal cancer and high and low grade dysplasia. The LIFE-GI system was also applied to the early detection of remnant lesions after endoscopic treatment of early gastric cancer and to the detection of laterally spreading superficial colonic tumors.
This system has potential application for the diagnosis of dysplastic lesions and early cancers in the gastrointestinal tract as an adjunct to ordinary white light endoscopy. This system, which needs no administration of a photosensitive agent, may be suitable as a screening method for the early detection of neoplastic tissues.
PMCID: PMC2362619  PMID: 18493491
17.  Appropriate use of endoscopy in the diagnosis and treatment of gastrointestinal diseases: up-to-date indications for primary care providers 
The field of endoscopy has revolutionized the diagnosis and treatment of gastrointestinal (GI) diseases in recent years. Besides the ‘traditional’ endoscopic procedures (esophagogastroduodenoscopy, colonoscopy, flexible sigmoidoscopy, and endoscopic retrograde cholangiopancreatography), advances in imaging technology (endoscopic ultrasonography, wireless capsule endoscopy, and double balloon enteroscopy) have allowed GI specialists to detect and manage disorders throughout the digestive system. This article reviews various endoscopic procedures and provides up-to-date endoscopic indications based on the recommendations of American Society for Gastrointestinal Endoscopy and American Cancer Society for primary care providers in order to achieve high-quality and cost-effective care.
PMCID: PMC2990396  PMID: 21116340
endoscopy; endoscopic indications; endoscopic procedures; imaging; primary care; gastrointestinal disorders; appropriate use
18.  Indicators of safety compromise in gastrointestinal endoscopy 
The growth in the use of endoscopy to diagnose and treat many gastointestinal disorders, and its central role in cancer screening programs, has led to a significant increase in the number of procedures performed. This growth, however, has also led to many variations in, among others, the provision of services, the choice of sedative medications and the training of providers. The recognition of the significance of quality in endoscopy has prompted several countries, including Canada, to initiate efforts to adopt nationwide quality improvement programs. The Canadian Association of Gastroenterology formed a committee to review endoscopy and quality with the aim of stimulating improvement. This article focuses specifically on patient safety indicators that were developed at a consensus conference aimed at generating a broad range of recommendations for selected endoscopic procedures, which if adopted, could lead to significant changes in how endoscopy services are provided.
The importance of quality indicators has become increasingly recognized in gastrointestinal endoscopy. Patient safety requires the identification and monitoring of occurrences associated with harm or the potential for harm. The identification of relevant indicators of safety compromise is, therefore, a critical element that is key to the effective implementation of endoscopy quality improvement programs.
To identify key indicators of safety compromise in gastrointestinal endoscopy.
The Canadian Association of Gastroenterology Safety and Quality Indicators in Endoscopy Consensus Group was formed to address issues of quality in endoscopy. A subcommittee was formed to identify key safety indicators. A systematic literature review was undertaken, and articles pertinent to safety in endoscopy were identified and reviewed. All complications and measures used to document safety were recorded. From this, a preliminary list of 16 indicators was compiled and presented to the 35-person consensus group during a three-day meeting. A revised list of 20 items was subsequently put to the consensus group for vote for inclusion on the final list of safety indicators. Items were retained only if the consensus group highly agreed on their importance.
A total of 19 indicators of safety compromise were retained and grouped into the three following categories: medication-related – the need for CPR, use of reversal agents, hypoxia, hypotension, hypertension, sedation doses in patients older than 70 years of age, allergic reactions and laryngospasm/bronchospasm; procedure-related early – perforation, immediate postpolypectomy bleeding, need for hospital admission or transfer to emergency department from the gastroenterology unit, instrument impaction, severe persistent abdominal pain requiring evaluation proven to not be perforation; and procedure-related delayed – death within 30 days of procedure, 14-day unplanned hospitalization, 14-day unplanned contact with a health provider, gastrointestinal bleeding within 14 days of procedure, infection or symptomatic metabolic complications.
The 19 indicators of safety compromise in endoscopy, identified by a rigorous, evidence-based consensus process, provide clear outcomes to be recorded by all facilities as part of their continuing quality improvement programs.
PMCID: PMC3275408  PMID: 22312605
Digestive system; Endoscopy; Health care; Quality assurance; Surgical complications; Safety
19.  New endoscopic and cytologic tools for cancer surveillance in the digestive tract 
Cancer surveillance is an increasing part of everyday practice in gastrointestinal endoscopy due to the identification of high risk groups from genetic and biomarker testing, genealogic and epidemiologic studies, and the increasing number of cancer survivors. An efficient surveillance program requires a cost-effective means for image-guided cancer detection and biopsy. A laser-based tethered-capsule endoscope with enhanced spectral imaging is introduced for unsedated surveillance of the lower esophagus. An ultrathin version of this same endoscope technology provides a 1.2-mm guidewire with imaging capability and cannula-style tools are proposed for image-guided biopsy. Advanced 3D cell visualization techniques are described for increasing the sensitivity of early cancer diagnosis from hematoxylin-stained cells sampled from the pancreatic and biliary ducts.
PMCID: PMC2679952  PMID: 19423026
endoscope; biopsy; image-guided intervention; 3D cytology; cancer surveillance
20.  Optical Molecular Imaging in the Gastrointestinal Tract 
Recent developments in optical molecular imaging allow for real-time identification of morphological and biochemical changes in tissue associated with gastrointestinal neoplasia. This review summarizes widefield and high resolution imaging modalities currently in pre-clinical and clinical evaluation for the detection of colorectal cancer and esophageal cancer. Widefield techniques discussed include high definition white light endoscopy, narrow band imaging, autofluoresence imaging, and chromoendoscopy; high resolution techniques discussed include probe-based confocal laser endomicroscopy, high-resolution microendoscopy, and optical coherence tomography. Finally, new approaches to enhance image contrast using vital dyes and molecular-specific targeted contrast agents are evaluated.
PMCID: PMC3746803  PMID: 23735112
optical molecular imaging; white light endoscopy; narrow band imaging; autofluorescence imaging; chromoendoscopy; confocal laser endomicroscopy; high resolution microendoscopy; optical coherence tomography
21.  Diagnosis of gastric intraepithelial neoplasia by narrow-band imaging and confocal laser endomicroscopy 
AIM: To evaluate the diagnosis of different differentiated gastric intraepithelial neoplasia (IN) by magnification endoscopy combined with narrow-band imaging (ME-NBI) and confocal laser endomicroscopy (CLE).
METHODS: Eligible patients with suspected gastric IN lesions previously diagnosed by endoscopy in secondary hospitals and scheduled for further diagnosis and treatment were recruited for this study. Excluded from the study were patients who had liver cirrhosis, impaired renal function, acute gastrointestinal (GI) bleeding, coagulopathy, esophageal varices, jaundice, and GI post-surgery. Also excluded were those who were pregnant, breastfeeding, were younger than 18 years old, or were unable to provide informed consent. All patients had all mucus and bile cleared from their stomachs. They then received upper GI endoscopy. When a mucosal lesion is found during observation with white-light imaging, the lesion is visualized using maximal magnification, employing gradual movement of the tip of the endoscope to bring the image into focus. Saved images are analyzed. Confocal images were evaluated by two endoscopists (Huang J and Li MY), who were familiar with CLE, blinded to the related information about the lesions, and asked to classify each lesion as either a low grade dysplasia (LGD) or high grade dysplasia (HGD) according to given criteria. The results were compared with the final histopathologic diagnosis. ME-NBI images were evaluated by two endoscopists (Lu ZS and Ling-Hu EQ) who were familiar with NBI, blinded to the related information about the lesions and CLE images, and were asked to classify each lesion as a LGD or HGD according to the “microvascular pattern and surface pattern” classification system. The results were compared with the final histopathologic diagnosis.
RESULTS: The study included 32 pathology-proven low grade gastric IN and 26 pathology-proven high grade gastric IN that were detected with any of the modalities. CLE and ME-NBI enabled clear visualization of the vascular microsurface patterns and microvascular structures of the gastric mucosa. The accuracy of the CLE and the ME-NBI diagnosis was 88% (95% CI: 78%-98%) and 81% (95% CI: 69%-93%), respectively. The kappa coefficient of agreement between the histopathology and the in vivo CLE imaging was 0.755; between the histopathology and the in vivo CLE imaging was 0.615. McNemar’s test (binomial distribution used) indicated that the agreement was significant (P < 0.05). When patients were diagnosed by ME-NBI with CLE, the overall accuracy of the diagnosis was 86.21% (95% CI: 73%-96%), and the kappa coefficient of agreement was 0.713, according to McNemar’s test (P < 0.05).
CONCLUSION: Higher diagnostic accuracy, sensitivity and specificity of CLE over ME-NBI indicate the feasibility of these two techniques for the efficacious diagnostic classification of gastric IN.
PMCID: PMC3442217  PMID: 23002348
Gastric intraepithelial neoplasia; Histological diagnosis; Confocal laser endomicroscopy; Magnification endoscopy; Narrow-band imaging; Gastric intraepithelial neoplasia lesion
22.  Esophageal squamous cell carcinoma - precursor lesions and early diagnosis 
Squamous cell carcinoma of the esophagus (SCCE) carries a poor prognosis due to late diagnosis. Early detection is highly desirable, since surgical and endoscopic resection offers the only possible cure for esophageal cancer. Population screening should be undertaken in high risk areas, and in low or moderate risk areas for people with risk factors (alcoholics, smokers, mate drinkers, history of head and neck cancer, achalasia and lye stricture of the esophagus). Esophageal balloon cytology is an easy and inexpensive sampling technique, but the current methods are insufficient for primary screening due to sampling errors. Conventional endoscopy with biopsy remains the standard procedure for the identification of pre-malignant and early malignant changes in esophageal mucosa and endoscopic detection. It may be enhanced by several techniques such as dye and optic chromoendoscopy, magnifying endoscopy, and optical-based spectroscopic and imaging modalities. Since more than 80% of SCCE deaths occur in developing countries, where expensive techniques such as narrow band imaging (NBI) and autofluorescence imaging are unavailable, the most cost-effective tool for targeting biopsies may be Lugol dye chromoendoscopy, since it is easy, accurate, inexpensive and available worldwide. In ideal conditions, or in developed countries, is it reasonable to think that optimal detection will require a combination of techniques, such as the combination of Lugol’s chromoendoscopy and NBI to identify esophageal areas that require further characterization by a high resolution technique. The efficacy and cost-effectiveness will determine whether these modalities will become part of standard endoscopy practice.
PMCID: PMC3262175  PMID: 22267978
Autofluorescence endoscopy; Early diagnosis; Esophageal cancer; Esophageal squamous cell carcinoma; Lugol’s solution; Narrow-band imaging endoscopy
23.  Targeted Imaging of Flat and Depressed Colonic Neoplasms 
Molecular imaging is a rapidly growing new discipline in gastrointestinal endoscopy that involves the development of novel imaging probes and instruments to visualize the molecular expression pattern of mucosa in the digestive tract. Several platforms for imaging agents, including antibody and peptide, are being developed to target over expressed biomolecules in cancer. In addition, novel imaging instruments, including fluorescence endoscopy and confocal microscopy, are being developed to provide wide area surveillance and microscopic examination. These methods are being applied to detect the presence of flat and depressed colonic neoplasms and to identify the tumor margins.
PMCID: PMC2962867  PMID: 20656254
molecular imaging; colonic neoplasms; dysplasia; flat and depressed; targets
24.  Small Bowel Endoscopy in Inflammatory Bowel Disease 
Clinical Endoscopy  2013;46(4):321-326.
Crohn disease (CD) is a chronic inflammatory bowel disease that affects the entire gastrointestinal tract but is most frequently localized to the large and small bowel. Small bowel endoscopy helps with the differential diagnosis of CD in suspected CD patients. Early diagnosis of CD is preferable for suspected CD conditions to improve chronic inflammatory infiltrates, fibrosis. Small bowel endoscopy can help with the early detection of active disease, thus leading to early therapy before the onset of clinical symptoms of established CD. Some patients with CD have mucosal inflammatory changes not in the terminal ileum but in the proximal small bowel. Conventional ileocolonoscopy cannot detect ileal involvement proximal to the terminal ileum. Small bowel endoscopy, however, can be useful for evaluating these small bowel involvements in patients with CD. Small bowel endoscopy by endoscopic balloon dilation (EBD) enables the treatment of small bowel strictures in patients with CD. However, many practical issues still need to be addressed, such as endoscopic findings for early detection of CD, application compared with other imaging modalities, determination of the appropriate interval for endoscopic surveillance of small bowel lesions in patients with CD, and long-term prognosis after EBD.
PMCID: PMC3746136  PMID: 23964328
Crohn disease; Capsule endoscopy; Balloon assisted endoscopy; Endoscopic balloon dilation
25.  Accuracy of endoscopic diagnosis of Helicobacter pylori infection according to level of endoscopic experience and the effect of training 
BMC Gastroenterology  2013;13:128.
Accurate prediction of Helicobacter pylori infection status on endoscopic images can contribute to early detection of gastric cancer, especially in Asia. We identified the diagnostic yield of endoscopy for H. pylori infection at various endoscopist career levels and the effect of two years of training on diagnostic yield.
A total of 77 consecutive patients who underwent endoscopy were analyzed. H. pylori infection status was determined by histology, serology, and the urea breast test and categorized as H. pylori-uninfected, -infected, or -eradicated. Distinctive endoscopic findings were judged by six physicians at different career levels: beginner (<500 endoscopies), intermediate (1500–5000), and advanced (>5000). Diagnostic yield and inter- and intra-observer agreement on H. pylori infection status were evaluated. Values were compared between the two beginners after two years of training. The kappa (K) statistic was used to calculate agreement.
For all physicians, the diagnostic yield was 88.9% for H. pylori-uninfected, 62.1% for H. pylori-infected, and 55.8% for H. pylori-eradicated. Intra-observer agreement for H. pylori infection status was good (K > 0.6) for all physicians, while inter-observer agreement was lower (K = 0.46) for beginners than for intermediate and advanced (K > 0.6). For all physicians, good inter-observer agreement in endoscopic findings was seen for atrophic change (K = 0.69), regular arrangement of collecting venules (K = 0.63), and hemorrhage (K = 0.62). For beginners, the diagnostic yield of H. pylori-infected/eradicated status and inter-observer agreement of endoscopic findings were improved after two years of training.
The diagnostic yield of endoscopic diagnosis was high for H. pylori-uninfected cases, but was low for H. pylori-eradicated cases. In beginners, daily training on endoscopic findings improved the low diagnostic yield.
PMCID: PMC3765341  PMID: 23947684
Helicobacter pylori; Endoscopic training; Diagnostic yield; Endoscopic career level; Inter-observer agreement; Intra-observer agreement

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