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White-light endoscopy with biopsy is the current gold standard modality for detecting and diagnosing upper gastrointestinal (GI) pathology. However, missed lesions remain a challenge. To overcome interobserver variability and learning curve issues, artificial intelligence (AI) has recently been introduced to assist endoscopists in the detection and diagnosis of upper GI neoplasia. In contrast to AI in colonoscopy, current AI studies for upper GI endoscopy are smaller pilot studies. Researchers currently lack large volume, well-annotated, high-quality datasets in gastric cancer, dysplasia in Barrett's esophagus and early esophageal squamous cell cancer. This review will look at the latest studies of AI in upper GI endoscopy, discuss some of the challenges facing researchers, and predict what the future may hold in this rapidly changing field.

Barrett's esophagus (BE) is a premalignant condition associated with the development of esophageal adenocarcinoma (EAC). Over the past decade, BE and its associated neoplasia has increased in prevalence globally. Current surveillance guidelines aimed to detect and treat BE‐associated dysplasia early in the hope of improving the morbidity and mortality of the condition. However, due to the lack of long‐term data and the proven benefit that surveillance actually improves mortality from EAC, the guidelines of the United States and Europe are slightly different. This review will focus on discussing the surveillance strategy for BE appropriate for the Asian region, taking into account the unique epidemiologic features of this disease in the Asian region., Current surveillance guidelines aim to detect Barrett's esophagus‐associated dysplasia early. However, due to the lack of long‐term data, and proven benefit that surveillance actually improves mortality from esophageal adenocarcinoma, the guidelines coming from the US and Europe are slightly different. This review will discuss the surveillance strategy for Barrett's esophagus appropriate to the Asian region, taking into account the unique epidemiologic features of this disease in the Asian region.

Background Although endoscopic ultrasound (EUS) features and criteria have been described in chronic pancreatitis, challenges remain with interoperator variability and ease of adoption. The aim of this study was to define and validate the EUS features of chronic pancreatitis in a multicenter prospective study in Asia. Method The study was divided into two parts: the first part was conducted to derive the EUS features of chronic pancreatitis with adequate interoperator agreement; the second was to prospectively evaluate these features in a multicenter cross-sectional study and determine the optimal combination of features for the diagnosis of chronic pancreatitis. Prospectively enrolled cases had standard internationally validated radiologic or histologic features of chronic pancreatitis, and controls were patients without chronic pancreatitis who underwent EUS examination. Results The top six EUS features that had good interobserver agreement (mean kappa 0.73, range 0.60 – 0.90) were selected to be further evaluated in part II of the study. These included: hyperechoic foci with shadowing, lobularity with honeycombing, cysts, dilated main pancreatic duct, dilated side branches, and calculi in the main pancreatic duct. A total of 284 subjects (132 cases, 152 controls) were enrolled from 12 centers in Asia. All six features had high accuracy ranging from 63.3 % to 89.1 %. Two or more of these six EUS features accurately defined chronic pancreatitis (sensitivity 94.7 %, specificity 98.0 %), with an area under the receiver operating curve of 0.986. Conclusion This multicenter Asian study characterized and defined the EUS features of chronic pancreatitis. This provides a useful tool in clinical practice and further research in pancreatic cancer surveillance.

To study the impact of computer-aided detection (CADe) system on the detection rate of polyps and adenomas in colonoscopy.A total of 1026 patients were prospectively randomly scheduled for colonoscopy with (the CADe group, CADe) or without (the control group, CON) the aid of the CADe system, together with visual notification and voice alarm, so as to compare the detection rate of polyp.Compared with group CON, the detection rate of adenomas increased in group CADe, the average number of adenomas increased, the number of small adenomas increased, the number of proliferative polyps increased, and the differences were statistically significant (P0.001), but the comparison for the number of larger adenomas showed no significant difference between the groups (P0.05).The CADe system is feasible for increasing the detection of polyps and adenomas in colonoscopy.

Drainage of obstructed bile duct and pancreatic duct under endoscopic ultrasonography (EUS) guidance has evolved into viable techniques suitable for patients with failed endoscopic retrograde cholangiopancreatography (ERCP) and/or altered surgical anatomy. One of the major advantages of EUS guidance is the possibility of multiple access points depending upon patient and ductal anatomy. Unlike ERCP, an approachable papilla is not a requisite for successful EUS-guided biliary or pancreatic ductal drainage. Moreover, as the access is away from the papilla, there is the possibility of reduced pancreatitis. A variety of procedures have become available for EUS-guided drainage, and it is important to develop standard terminology and procedural details. EUS-specific stents, including lumen-apposing metal stents have recently become available, and are likely to impact the outcomes of these procedures. Available data show a high success rate and acceptable adverse event rate for EUS-guided biliary drainage. Success rate appears to be low for pancreatic duct drainage because of a variety of reasons. Outcomes of EUS-guided biliary drainage appear equivalent to percutaneous drainage and ERCP. EUS-guided gallbladder drainage appears promising for patients requiring gallbladder drainage but unfit for surgery. Further large controlled studies are needed to evaluate the exact role of these procedures.

'Adult' or 'somatic' stem cells harbor an intrinsic ability to regenerate tissues. Heterogeneity of such stem cells along the gastrointestinal tract yields the known segmental specificity of this organ and may contribute to the pathology of certain enteric conditions. Here we detail technology for the generation of 'libraries' of clonogenic cells from 1-mm-diamter endoscopic biopsy samples from the human gastrointestinal tract. Each of the 150-300 independent clones in a typical stem cell library can be clonally expanded to billions of cells in a few weeks while maintaining genomic stability and the ability to undergo multipotent differentiation to the specific epithelia from which the sample originated. The key to this methodology is the intrinsic immortality of normal intestinal stem cells (ISCs) and culture systems that maintain them as highly immature, ground-state ISCs marked by a single-cell clonogenicity of 70% and a corresponding 250-fold proliferative advantage over spheroid technologies. Clonal approaches such as this enhance the resolution of molecular genetics, make genome editing easier, and may be useful in regenerative medicine, unravelling heterogeneity in disease, and facilitating drug discovery.

// Rony K. Roy 1, * , Michal M. Hoppe 1, * , Supriya Srivastava 1 , Animesh Samanta 2 , Neel Sharma 3 , Kar Tong Tan 1 , Henry Yang 1 , Dominic C. Voon 1 , Brendan Pang 4 , Ming Teh 4 , Naoko Murata-Kamiya 5 , Masanori Hatakeyama 5 , Young-Tae Chang 2 , Wei Peng Yong 1, 6 , Yoshiaki Ito 1, 6 , Khek Yu Ho 2, 6 , Patrick Tan 1, 6 , Richie Soong 1 , Phillip H. Koeffler 1, 2 , Khay Guan Yeoh 2, 6 , Anand D. Jeyasekharan 1, 6 1 Cancer Science Institute of Singapore, National University of Singapore, Singapore 2 Department of Chemistry, National University of Singapore, Singapore 3 Division of Gastroenterology and Hepatology, National University Hospital, Singapore 4 Department of Pathology, National University Hospital, Singapore 5 University of Tokyo, Tokyo, Japan 6 Singapore Gastric Cancer Consortium, National University of Singapore, Singapore * These authors have contributed equally to this work Correspondence to: Khay Guan Yeoh, email: mdcykg@nus.edu.sg Anand D. Jeyasekharan, email: csiadj@nus.edu.sg Keywords: gastric cancer, biomarker, Helicobacter pylori, CEACAM6, endoscopy Received: February 19, 2016 Accepted: May 23, 2016 Published: July 11, 2016 ABSTRACT Early detection of gastric cancers saves lives, but remains a diagnostic challenge. In this study, we aimed to identify cell-surface biomarkers of early gastric cancer. We hypothesized that a subset of plasma membrane proteins induced by the Helicobacter pylori oncoprotein CagA will be retained in early gastric cancers through non-oncogene addiction. An inducible system for expression of CagA was used to identify differentially upregulated membrane protein transcripts in vitro . The top hits were then analyzed in gene expression datasets comparing transcriptome of gastric cancer with normal tissue, to focus on markers retained in cancer. Among the transcripts enriched upon CagA induction in vitro , a significant elevation of CEACAM6 was noted in gene expression datasets of gastric cancer. We used quantitative digital immunohistochemistry to measure CEACAM6 protein levels in tissue microarrays of gastric cancer. We demonstrate an increase in CEACAM6 in early gastric cancers, when compared to matched normal tissue, with an AUC of 0.83 for diagnostic validity. Finally, we show that a fluorescently conjugated CEACAM6 antibody binds avidly to freshly resected gastric cancer xenograft samples and can be detected by endoscopy in real time. Together, these results suggest that CEACAM6 upregulation is a cell surface response to H. pylori CagA, and is retained in early gastric cancers. They highlight a novel link between CEACAM6 expression and CagA in gastric cancer, and suggest CEACAM6 to be a promising biomarker to aid with the fluorescent endoscopic diagnosis of early neoplastic lesions in the stomach.

The incidence of esophageal adenocarcinoma is rapidly increasing in Western countries. This is despite the introduction of sophisticated endoscopic techniques and our ability to readily monitor the presumed precursor lesion known as Barrett’s esophagus. Preemptive approaches, including radiofrequency ablation (RFA), and photodynamic therapy (PDT) for Barrett’s esophagus and dysplasia are achieving dramatic initial results. Although the long-term efficacy of these nonspecific ablative therapies is awaiting longitudinal studies, reports of recurrences are increasing. More targeted therapies, particularly directed at the stem cells of Barrett’s esophagus, demand knowing the origin of this intestinal metaplasia (IM). The prevailing concept holds that Barrett’s esophagus arises from the “transcommitment” of esophageal stem cells to produce an intestine-like epithelium. An alternative explanation derives from the discovery of a discrete population of residual embryonic cells (RECs) existing at the gastroesophageal junction in normal individuals that expands and colonizes regions of the esophagus denuded by chronic reflux. These RECs form IM within days of esophageal injury, suggesting a novel mechanism of tumorigenesis.

This study aims to assess the clinical utility of a rapid fiber-optic Raman spectroscopy technique developed for enhancingin vivodiagnosis of gastric precancer during endoscopic examination. We have developed a real-time fiber-optic Raman spectroscopy system capable of simultaneously acquiring both fingerprint (FP) (i.e., 800–1800 cm−1) and high-wavenumber (HW) (i.e., 2800–3600 cm−1) Raman spectra from gastric tissuein vivoat endoscopy. A total of 5792 high-qualityin vivoFP/HW Raman spectra (normal (n= 5160); dysplasia (n= 155), and adenocarcinoma (n= 477)) were acquired in real-time from 441 tissue sites (normal (n= 396); dysplasia (n= 11), and adenocarcinoma (n= 34)) of 191 gastric patients (normal (n= 172); dysplasia (n= 6), and adenocarcinoma (n= 13)) undergoing routine endoscopic examinations. Partial least squares discriminant analysis (PLS-DA) together with leave-one-patient-out cross validation (LOPCV) were implemented to develop robust spectral diagnostic models. The FP/HW Raman spectra differ significantly between normal, dysplasia and adenocarcinoma of the stomach, which can be attributed to changes in proteins, lipids, nucleic acids, and the bound water content. PLS-DA and LOPCV show that the fiber-optic FP/HW Raman spectroscopy provides diagnostic sensitivities of 96.0%, 81.8% and 88.2%, and specificities of 86.7%, 95.3% and 95.6%, respectively, for the classification of normal, dysplastic and cancerous gastric tissue, superior to either the FP or HW Raman techniques alone. Further dichotomous PLS-DA analysis yields a sensitivity of 90.9% (10/11) and specificity of 95.9% (380/396) for the detection of gastric dysplasia using FP/HW Raman spectroscopy, substantiating its clinical advantages over white light reflectance endoscopy (sensitivity: 90.9% (10/11), and specificity: 51.0% (202/396)). This work demonstrates that the fiber-optic FP/HW Raman spectroscopy technique has great promise for enhancingin vivodiagnosis of gastric precancer during routine endoscopic examination.

Over the past few years, the definition of Barrett's oesophagus has altered with no real agreement on histological understanding. This article highlights the increasing confusion regarding Barrett's oesophagus with a focus on the all-too-frequently ignored aspect of the columnar lined oesophagus.

Background: Endoscopic retrograde cholangiopancreatography (ERCP) is a common technique for assessing the pancreas and the biliary system; however, the potential complications have raised concern among endoscopists and patients. Recently, the need of endoscopic ultrasound (EUS) as an additional tool of assessment before the ERCP procedure has been increasing. The need of EUS in developing countries is still a matter of debate regarding the cost, investment, and training. Here, we report the significant impact of EUS on several unselected interesting cases of pancreatobiliary disorders. Method: We selected several interesting cases from the patients who underwent EUS at our private hospital in Jakarta, Indonesia. The EUS procedures were performed by one experienced endosonographer and one EUS trainee who are very experienced with transabdominal ultrasound. The equipment was an Olympus JF UCT 180 EUS scope which was connected to an Aloka IPF-1701C ultrasound machine (Tokyo, Japan). Results: Five interesting cases were included from patients who underwent EUS due to pancreatobiliary disorders. The cases included recurrent pancreatitis due to pancreatic stone at the small branch that obstructed the main pancreatic duct, common bile duct (CBD) stone with insignificant duct dilatation, pancreatic head cancer with total obstruction at the distal CBD and portal vein infiltration, pancreas divisum in a young girl, and distal CBD mass that caused obstructive jaundice. Conclusions: The EUS procedure has shown a significant impact in managing patients with pancreatobiliary diseases. In most developing countries, EUS needs to be evaluated further regarding the cost, investment, and training.

In Asia, the prevalence of Barrett’s esophagus derived from study of subjects undergoing endoscopy investigation is low compared to rates reported in Europe and North America. In Southeast and East Asia, where most of the existing data in Asia has been gathered, the prevalence of Barrett’s esophagus in various populations studied mostly remains below 5%. As detection and, thereafter, diagnosis of Barrett’s esophagus are highly dependent on recognition of the condition, there is evidence that lack of awareness of the condition in the region could have resulted in underdiagnosis of the disease. Despite this, the prevalence of Barrett’s esophagus is beginning to rise in some parts of Asia.

Background and study aims Linear endoscopic ultrasound (EUS) evaluation of the pancreaticobiliary system usually requires scanning from both the stomach and the duodenum. The feasibility of assessing the complete pancreaticobiliary system from the stomach alone has not been studied. We aimed to conceptualize a system-based approach (the railroad approach) for linear pancreaticobiliary EUS (PB-EUS) and evaluate whether the pancreaticobiliary anatomy could be assessed from the stomach alone. Patients and methods Three maneuvers were conceptualized and evaluated (the alpha maneuver in the stomach, and sigma and xi maneuvers in the duodenum). The maneuvers were prospectively evaluated in 100 consecutive patients requiring PB-EUS. Results The median procedure time for the three maneuvers was significantly higher than that for the alpha maneuver alone (12 vs. 6 minutes; P ≤ 0.001). The visualization rate of the hilum and common hepatic duct was significantly higher from the stomach than from the duodenum (100 % vs. 83.5 %; P ≤ 0.001), while rates for the head of the pancreas (100 % vs 100 %) and uncinate process (100 % vs 100 %) did not differ. The suprapancreatic common bile duct (CBD; 92 % vs 100 %; P = 0.006), retropancreatic CBD (95 % vs 100 %; P = 0.06), and pancreatic duct in the head (94 % vs 100 %; P = 0.03) were not completely visualized from the stomach, because of pancreatic calcification or shadow from the ligaments. The EUS diagnosis made from the stomach and duodenum did not differ after excluding body and tail lesions (pancreatic head neoplasms, 100 % vs 100 %; CBD stone, 100 % vs 84.6 %; pancreatic cysts in the head, 83.3 % vs 83.3 %, respectively). Conclusions Adequate anatomical and diagnostic information on the pancreaticobiliary system may be acquired by EUS scanning from the stomach alone and with a shorter procedure time.

ObjectivesInterventional endoscopic ultrasonography (EUS) procedures are gaining popularity and the most commonly performed procedures include EUS-guided drainage of pancreatic pseudocyst, EUS-guided biliary drainage, EUS-guided pancreatic duct drainage and EUS-guided celiac plexus ablation. The aim of this paper is to formulate a set of practice guidelines addressing various aspects of the above procedures.MethodsFormulation of the guidelines was based on the best scientific evidence available. The RAND/UCLA appropriateness methodology (RAM) was used. Panellists recruited comprised experts in surgery, interventional EUS, interventional radiology and oncology from 11 countries. Between June 2014 and October 2016, the panellists met in meetings to discuss and vote on the clinical scenarios for each of the interventional EUS procedures in question.ResultsA total of 15 statements on EUS-guided drainage of pancreatic pseudocyst, 15 statements on EUS-guided biliary drainage, 12 statements on EUS-guided pancreatic duct drainage and 14 statements on EUS-guided celiac plexus ablation were formulated. The statements addressed the indications for the procedures, technical aspects, pre- and post-procedural management, management of complications, and competency and training in the procedures. All statements except one were found to be appropriate. Randomised studies to address clinical questions in a number of aspects of the procedures are urgently required.ConclusionsThe current guidelines on interventional EUS procedures are the first published by an endoscopic society. These guidelines provide an in-depth review of the current evidence and standardise the management of the procedures.

This study aims to characterize the in vivo Raman spectroscopic properties of normal colorectal tissues and to assess distinctive biomolecular variations of different anatomical locations in the colorectum for cancer diagnosis. We have developed a novel 785 nm excitation fiber-optic Raman endoscope that can simultaneously acquire in vivo fingerprint (FP) spectra (800-1800 cm(-1)) and high-wavenumber (HW) Raman spectra (2800-3600 cm(-1)) from the subsurface of colorectal tissue. We applied the FP/HW Raman endoscope for in vivo tissue Raman measurements of various normal colorectal anatomical locations (i.e., ascending colon (n = 182), transverse colon (n = 249), descending colon (n = 124), sigmoid (n = 212), and rectum (n = 362)) in 50 subjects. Partial least-squares (PLS)-discriminant analysis (DA) was employed to evaluate the interanatomical variability. The normal colorectal tissue showed a subtle interanatomical variability in molecular constituents (i.e., proteins, lipids, and water content) and could be divided into three major clusterings: (1) ascending colon and transverse colon, (2) descending colon, and (3) sigmoid and rectum. The PLS-DA multiclass algorithms were able to identify different tissue sites with varying sensitivities (SE) and specificities (SP) (ascending colon: SE: 1.10%, SP: 91.02; transverse colon: SE: 14.06%, SP: 78.78; descending colon: SE: 40.32%, SP: 81.99; sigmoid: SE: 19.34%, SP: 87.90; rectum: SE: 71.55%, SP: 77.84). The interanatomical molecular variability was orders of magnitude less than neoplastic tissue transformation. Further PLS-DA modeling on in vivo FP/HW tissue Raman spectra yielded a diagnostic accuracy of 88.8% (sensitivity: 93.9% (93/99); specificity 88.3% (997/1129) for colorectal cancer detection. This work discloses that interanatomical Raman spectral variability of normal colorectal tissue is subtle compared to cancer tissue, and the simultaneous FP/HW Raman endoscopic technique has promising potential for real-time, in vivo diagnosis of colorectal cancer at the molecular level.

Background: There is a lack of consensus on how endoscopic ultrasound (EUS) guided pseudocyst drainage should be performed. This survey was carried out amongst members of the Asian Endoscopic Ultrasonography Group (AEG) to describe their practices in performing this procedure. Methods: This was an Asia wide multi-institutional survey amongst members of the Asian EUS group conducted between November and December 2013. The responses to a 19-question survey with regard to the practice of pseudocyst drainage were obtained. Results: In total, 19 endoscopists responded to the questionnaire and the mean (SD) number of procedures performed by each endoscopist was 87.95 (40); 42.2 % believed that prior endoscopic retrograde cholangiopancreatography (ERCP) is required and pancreatic duct stenting is indicated in patients with pancreatic duct disruption; 47.4 % used tapered catheters for track dilation and 42.1 % used the cystotome; 84.1 % would dilate the track up to 8 to 10 mm in size. Metallic stents were used by 10.5 % of the respondents and transcystic catheters were employed by 26.3 %. Those who were more experienced in the procedure tended to use the cystotome more frequently (P = 0.02) and removed the stents in less than 3 months after insertion (P = 0.011). Conclusion: This was the first Asia wide survey in the practice of pseudocyst drainage. There were wide variations in practice and randomized studies are urgently needed to establish the best approach for management of this condition. There is also a pressing need for establishment of a consensus for safe practices.

The best means to improve gastrointestinal cancer survival is screening and treatment of early lesions. In esophageal adenocarcinoma, it is believed that low-grade dysplasia and perhaps even high-risk Barrett's esophagus represent the most attractive targets for achieving a cure. An issue with Barrett's esophagus is that endoscopy alone cannot distinguish Barrett's esophagus from columnar-lined epithelium or from areas of low-grade dysplasia. Much effort, therefore, has been devoted to discover molecular biomarkers of high-risk states and to develop imaging tools for detecting these biomarkers in a manner that could assist real-time in vivo targeting of sites for biopsy. The strategy we have used is to generate stem cell clones from Barrett's esophagus biopsy specimens and to compare their gene expression profiles with patient-matched stem cell clones of the esophageal squamous epithelia and gastric cardia. It is anticipated that by mining the expression data sets of these Barrett's stem cell clones, we will be able to identify unique cell surface markers of the Barrett's stem cells against which cytotoxic antibodies or aptamers can be developed and used to aid the endoscopist in identifying regions of atypia for biopsy, perform a real-time diagnosis, stratify patients during the examination, and, ultimately, direct therapy in a preemptive manner.

In Asia, the incidence of pancreatic cancer in some countries has been increasing. Owing to most cases being diagnosed late, prognosis for pancreatic cancer remains dismal. It is clear that the future for pancreatic cancer lies in early detection. While the possible presence of pancreatic masses is often first raised by non-invasive abdominal imaging, such as computerized tomography and magnetic resonance imaging, smaller lesions and locoregional lymph node metastases are often not detectable by these means. Endoscopic ultrasonography (EUS) offers a higher sensitivity (93–100%) for detection of small potentially curable pancreatic masses than other existing imaging modalities. It is also recommended for the evaluation of portal vein confluence, portal vein, celiac axis, and superior mesentric artery origin, and exclusion of resectability. Due to the closer proximity of EUS to the target structure, and lower rate of needle tract seeding, EUS-guided fine-needle aspiration of pancreatic mass is considered the most suitable tissue acquisition technique. Lastly, EUS also enables the performance of endoscopic interventions. Its performance can be further enhanced with newer techniques, including contrast-enhanced ultrasound and elastrography. It is anticipated that in the near future, molecular technologies may make it possible to detect microscopic amounts of cancer in tissue or blood, predict relapse and survival after therapy, as well as determine optimal therapy.

Despite the widespread practice of endoscopic surveillance for Barrett's esophagus in the West, this strategy has not been shown to reduce mortality from esophageal adenocarcinoma. Coupled with the very low absolute annual risk of Barrett's adenocarcinoma of 0.1%, this has called into question as to whether Barrett's esophagus is an over-hyped condition in the West. On the contrary, it is widely assumed that the prevalence of Barrett's esophagus is low in Asia. Could there be under-recognition of Barrett's esophagus, resulting in the underdiagnosis of the disease in the region? Our own study noted a much higher prevalence of histologically confirmed Barrett's esophagus following increased interest in endoscopic investigation of this disease, suggesting the low prevalence of Barrett's esophagus reported in most parts of Asia could have been attributed, at least in part, to underdiagnosis and/or lack of awareness of the condition. Training in the use of standardized diagnostic criteria could enhance diagnosis of the disease. In a recent study conducted by the Asia-Pacific Barrett's Consortium, formal training in the endoscopic recognition of columnar-lined Barrett's segment enhanced endoscopists' detection of the disease and led to significantly higher diagnostic yield (1.5% vs 0.42% in untrained endoscopists). The use of advanced endoscopic imaging technology such as narrow-band imaging improved the negative predictive value in the diagnosis of Barrett's esophagus's associated neoplasia. Raman spectroscopy, a novel biomolecular probe-based technology that does not rely upon operator's interpretation of images, could potentially enhance the detection of Barrett's esophagus and associated neoplasia.

Introduction Barrett's esophagus (BE) is a premalignant condition associated with esophageal adenocarcinoma (EAC). Evidence highlights that EAC is associated with an estimated 5-year survival of approximately 10–15%. Therefore, there is a need to determine which biomarkers are of value in the diagnosis of BE and beyond. The aim of our study was to evaluate the clinical significance of markers known to be expressed across BE and associated neoplasia. Methods Retrospective tissues were obtained from columnar lined esophagus (CLE) without goblet cells (n = 22), BE (n = 29), dysplasia (n = 14), and EAC (n = 10). Standardised immunohistochemistry for FABP1, Hepar, CDH17, and CDX2 were performed followed by quantitative staining and statistical analysis. Results FABP1 expression was negligible in CLE and was highest in BE, with a further decrease in expression in dysplasia and EAC. Hepar expression was also negligible in CLE and was highest in dysplasia and BE, with a reduced expression in EAC. CDH17 and CDX2 showed a significantly higher expression in BE, dysplasia, and EAC compared to CLE. Conclusion All 4 markers were excellent diagnostic panels to clearly discriminate BE from CLE. Moreover, as FABP1 and Hepar have different expression levels in dysplasia and EAC, these markers could function as key diagnostic aids in helping to determine the state of disease progression.

Barrett's esophagus (BE) is a premalignant condition associated with the development of esophageal adenocarcinoma (EAC). Despite the low risk of progression to EAC, evidence highlights the notably poor survival rates of this malignancy. The mainstay form of diagnosis of BE is endoscopy and biopsy sampling. However, research emphasizes limitations with regards to the histological detection of BE and associated dysplasia. The aim of this study is to evaluate the clinical significance of CEACAM6 as a potential biomarker for the diagnosis of BE and beyond. Retrospective tissue samples were obtained from columnar lined esophagus without goblet cells (n = 27), BE (n = 18), BE associated dysplasia (n = 16), and EAC (n = 24). Standardized immunohistochemistry for CEACAM6 was performed followed by quantitative staining analysis. Statistical analysis across the BE spectrum for CEACAM6 was undertaken and a P value

Background and Aim: With the rising incidence of digestive cancers in the Asia Pacific region and the advancement in diagnosis, management and palliation in these conditions, the clinical burden on oncologists is ever increasing. This Summit meeting was called to discuss the optimal management of digestive cancers and the role of Gastroenterologists Method: Experts from Asia Pacific countries in the fields of medical, oncologic, surgical and endoscopic management of cancers in the esophagus, stomach, colon/rectum and the liver reviewed the literature and their practice. 18 position statements were drafted, debated and voted. Results: It was agreed that the burden on GI cancer is increasing. More research will be warranted on chemotherapy, chemoprevention, cost-effectiveness of treatment and nutrition. Cancer management guidelines should be developed in this region when more clinical data are available. In order to improve care to patients, a multi-disciplinary team coordinated by a “cancer therapist” is proposed. This cancer therapist can be a gastroenterologist, a surgeon or any related discipline who have acquired core competence training. This training should include an attachment in a center-of-excellence in cancer management for no less than 12 months. Conclusion: The management of GI cancer should be an integrated multi-disciplinary approach and training for GI cancer therapists should be provided for.

Background Sensory sensitization is one of the main pathophysiological hypotheses in functional gastrointestinal disorders (FGIDs). As sensitization may affect various sensory modalities, we aimed to develop a reproducible gastric pain model utilizing polymodal pathways for use in functional and other pain disorders. Methods In this double-blind, cross-over study 42 healthy subjects swallowed one capsule containing either capsaicin 0.5 mg or nocebo every 15 min until moderate pain (intensity >30 on 100 mm visual analogue scale) was attained for at least 5 min. Pain was rated every minute. Capsaicin titration was repeated thrice for reliability calculation. Key Results Moderate pain in the upper abdomen was successfully achieved in 38 of 42 subjects (90%) with capsaicin titration and in one of 42 (2%) with nocebo. The median dosage required to induce moderate pain for at least 5 min was two capsules (interquartile range 1–3) and the median gastric pain intensity was 47 (41–53). The median duration of moderate pain was 8 min (5–12). Moderate pain was successfully reproduced with capsaicin in all subjects on study days 2 and 3, with an excellent Cronbach reliability coefficient of >0.8. Conclusions & Inferences Standardized gastric pain can be conveniently achieved in a majority of healthy subjects using a simple oral capsaicin titration, with minimal adverse events. The between-test reproducibility is high and nocebo responses are negligible. This technique stimulating a multimodal physiological pathway will be useful in the investigation of sensory changes in FGIDs, including functional dyspepsia.

SummaryBarrett's esophagus is an intestine-like metaplasia and precursor of esophageal adenocarcinoma. Triggered by gastroesophageal reflux disease, the origin of this metaplasia remains unknown. p63-deficient mice, which lack squamous epithelia, may model acid-reflux damage. We show here that p63 null embryos rapidly develop intestine-like metaplasia with gene expression profiles similar to Barrett's metaplasia. We track its source to a unique embryonic epithelium that is normally undermined and replaced by p63-expressing cells. Significantly, we show that a discrete population of these embryonic cells persists in adult mice and humans at the squamocolumnar junction, the source of Barrett's metaplasia. We show that upon programmed damage to the squamous epithelium, these embryonic cells migrate toward adjacent, specialized squamous cells in a process that may recapitulate early Barrett's. Our findings suggest that certain precancerous lesions, such as Barrett's, initiate not from genetic alterations but from competitive interactions between cell lineages driven by opportunity.PaperClip

Gastroesophageal reflux disease (GERD) is a known predisposing factor for Barrett's esophagus. Amongst individuals with symptomatic GERD, the prevalence of Barrett esophagus is estimated to be more than 10%, and an individual with Barrett's esophagus is more likely than the general population to develop esophageal adenocarcinoma. In Western Europe and North America, incidence of esophageal adenocarcinoma had been on the upward trend for many decades. In comparison, although the prevalence of GERD and reflux esophagitis has increased several fold in some parts of Asia, the prevalence of esophageal adenocarcinoma and Barrett's esophagus remains generally low in the region. Rising incidence of esophageal adenocarcinoma has been observed in regions witnessing increasing prevalence of GERD. If the recent increase in prevalence of GERD in parts of urbanized Asia is any indication of the beginning of an upsurge in the incidence of Barrett's esophagus and associated adenocarcinoma, would we be witnessing a pattern of epidemiological shift mirroring that in the West? Given that more than 90% of Barrett's esophagus in Asian patients is of the short-segment type, which is reported to have lesser propensity to develop to adenocarcinoma, could the ongoing epidemiologic transition take Asia on the same trail as that which the West has taken? This article will draw on relevant findings from various parts of Asia and take an in-depth look at prevailing disease trends to see where Asia stands now in the changing epidemiology of GERD, Barrett's esophagus and associated adenocarcinoma.

In Western countries, the epidemiology of esophageal cancer has changed considerably over the past decades with a rise in the ratio of adenocarcinoma to squamous cell carcinoma. Although the prevalence of gastroesophageal reflux is increasing in Asia, the prevalences of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) have remained low in most Asian countries. The Asian Barrett's Consortium recently conducted a review of published studies on BE from Asia to assess the current status of BE research in Asia, and to recommend potential areas for future BE research in the region. Differences in study design, enrolled population, and endoscopic biopsy protocols used have led to substantial variability in the reported BE prevalence (0.06% to 19.9%) across Asia. In particular, some Japanese studies used diagnostic criteria that differed considerably from what was used in most Asian studies. As in Western countries, increased age, male sex, tobacco smoking, reflux symptoms, and erosive esophagitis have been found to be risk factors for BE in several case-control studies from Asia. The Prague C and M criteria, developed to provide better interobserver reliability in diagnosis and grading of BE, are currently under extensive evaluation in the Asian population. There is a need for standardized protocols for endoscopic and histopathologic diagnosis before initiating collaborative projects to identify etiologic determinants of BE and its ensuing malignant transformation. At present, data regarding the management and long-term outcome of BE are extremely limited in Asia. More studies of BE in this geographic area are warranted.

This study explores the utility of a novel image-guided Raman endoscopy technique for in vivo distinction of gastric cancer from normal tissue during clinical gastroscopy. The rapid-acquisition fiber-optic Raman endoscopy system developed was employed for in vivo gastric tissue Raman measurements at 785 nm laser excitation. A total of 1063 in vivo Raman spectra were acquired from 238 tissue sites of 67 gastric patients who underwent endoscopic ultrasound staging procedure, in which 934 Raman spectra were from 121 normal tissue sites whereas 129 Raman spectra were from 117 neoplastic gastric tissue sites. Gastric Raman spectra were fitted and reconstructed by using a linear combination of the eight basis reference spectra from the biochemicals (i.e., actin, albumin, collagen, DNA, histones, pepsinogen, phospholipids and triolein) in gastric tissue and also compared with the in vivo gastric Raman spectra measured. The resulting fit coefficients were further utilized through recursive partitioning techniques to develop diagnostic algorithms for gastric cancer diagnosis. High-quality in vivo Raman spectra in the range of 800-1800 cm(-1) can be acquired from gastric mucosa within 0.5s. The fit coefficients from albumin, nucleic acid, phospholipids and histones were found to be the most significant features for construction of the diagnostic model, giving rise to an overall accuracy of 93.7% (i.e., sensitivity of 94.0% (110/117) and specificity of 93.4% (113/121)) for in vivo discrimination of cancerous tissue from normal gastric tissue after the leave-one tissue site-out, cross-validation technique. This work demonstrates for the first time that image-guided Raman endoscopy technique has promising potential for the non-invasive, in vivo diagnosis and detection of gastric cancer at the molecular level.

Background The aim of this study was to evaluate the feasibility of using near-infrared (NIR) Raman spectroscopy for early diagnosis and typing of intestinal and diffuse adenocarcinoma of the stomach. Methods A dispersive-type NIR Raman system was used for tissue measurements. One hundred gastric tissue samples from 62 patients who underwent endoscopy or gastrectomy were used (70 normal tissue specimens and 30 adenocarcinomas). Principal components analysis (PCA) and multinomial logistic regression (MNLR) were used to develop diagnostic algorithms for tissue classification. Results High-quality Raman spectra ranging from 800 to 1800 cm−1 were acquired from gastric tissue within 5 s. There were significant differences in Raman spectra between normal stomach and the two gastric adenocarcinoma subtypes, particularly in the spectral ranges 850–1150, 1200–1500 and 1600–1750 cm−1, which contain signals related to proteins, nucleic acids and lipids. PCA–MNLR achieved predictive accuracies of 88, 92 and 94 per cent for normal stomach, and intestinal- and diffuse-type gastric adenocarcinomas respectively. Conclusion NIR Raman spectroscopy can detect gastric malignancy and identify the subtype of gastric adenocarcinoma.

Raman spectroscopy is a unique vibrational spectroscopic technique which can be used to probe biochemicals and biomolecular structures and conformations of tissues. The main objective of this study is to evaluate the feasibility of applying near-infrared (NIR) Raman spectroscopy for identification of nonneoplastic lesions (Helicobacter-pylori (Hp) infection, and intestinal metaplasia (IM)) highly associated with stomach cancer. A rapid-acquisition NIR Raman spectroscopic system was used for tissue Raman measurements at 785 nm excitation, and a total of 88 gastric tissue samples (57 normal; 11 Hp-infection; 20 IM) from 56 patients were measured. The principal components analysis (PCA) and linear discriminant analysis (LDA) techniques were implemented to develop effective diagnostic algorithms for classification of Raman spectra of different gastric tissue types. High-quality Raman spectra in the range of 800-1800 cm(-1) were acquired from gastric tissue within 5 seconds. Significant spectral differences in Raman spectra were observed among normal, Hp-infection and IM gastric tissue, particularly in the spectral ranges of 848-917, 960-1015, 1088-1133, 1206-1213, 1277-1313, 1395-1445, 1517-1549, 1607-1690, and 1714-1767 cm(-1) which contained signals related to proteins, lipids and porphyrin. PCA-LDA algorithms developed together with leave one patient out, cross validation technique yield diagnostic sensitivities of 91.7%, 80.0%, and 80.0%, and specificities of 80.0%, 100%, and 92.7%, respectively, for classification of normal, Hp-infection and IM gastric tissues. This work demonstrates the utility of NIR Raman spectroscopy for early diagnosis of Hp-infection and IM lesions in the gastric at the molecular level.

Natural orifice transluminal endoscopic surgery (NOTES) has gained widespread interest as a potentially alternative to laparoscopic surgery, but concerns over peritoneal contaminations are unsolved. The aim of our study was to assess the safety of transluminal surgery by investigating the intraperitoneal bacterial load and contamination during transgastric and transvaginal surgeries. Twelve female pigs underwent transgastric (n = 7; tubal ligation and oophorectomy) and transvaginal procedures (n = 5; cholecystectomy). All animals were sacrificed after 2 weeks. The procedures were performed by using a double-channel endoscope (GIF-2T160; Olympus, Tokyo, Japan) under general anesthesia. Peritoneal fluid sampling was taken immediately after entry into the abdomen, at the end of the surgical procedure and during the autopsy, and sent for microbiologic assessment. In the transgastric group, 6 animals completed the surgical procedures and survived. Three pigs experienced signs of postoperative peritonitis with abscesses and adhesions visible and Escherichia Coli isolated at autopsy. In the transvaginal group, a cholecystectomy was performed without technical problems in all animals. No signs of postoperative sepsis nor growth in the microbiologic samples were recorded. In conclusion, the transvaginal approach seemed to be safer and produced less intra-abdominal contamination and sepsis, compared to the transgastric approach. Although both transgastric tubal ligation and oophorectomy and transvaginal cholecystectomy were feasible using equipment and accessories currently available for conventional endoscopy, new procedure-specific instruments and equipment should be developed to allow the operator safer access into the peritoneum.

Raman spectroscopy is a molecular vibrational spectroscopic technique that is capable of optically probing the biomolecular changes associated with neoplastic transformation. The purpose of this study was to apply near-infrared (NIR) Raman spectroscopy for differentiating dysplasia from normal gastric mucosa tissue. A total of 65 gastric mucosa tissues (44 normal and 21 dysplasia) were obtained from 35 patients who underwent endoscopy investigation or gastrectomy operation for this study. A rapid NIR Raman system was utilized for tissue Raman spectroscopic measurements at 785-nm laser excitation. High-quality Raman spectra in the range of 800–1800 cm−1 can be acquired from gastric mucosa tissue within 5 s. Raman spectra showed significant differences between normal and dysplastic tissue, particularly in the spectral ranges of 850–1150, 1200–1500 and 1600–1750 cm−1, which contained signals related to proteins, nucleic acids and lipids. The diagnostic decision algorithm based on the combination of Raman peak intensity ratios of I875/I1450 and I1208/I1655 and the logistic regression analysis yielded a diagnostic sensitivity of 90.5% and specificity of 90.9% for identification of gastric dysplasia tissue. This work demonstrates that NIR Raman spectroscopy in conjunction with intensity ratio algorithms has the potential for the noninvasive diagnosis and detection of precancer in the stomach at the molecular level. Copyright © 2009 John Wiley & Sons, Ltd.

Aim: To determine the inter-observer agreement and validity of the LA Classification in scoring the severity of esophagitis in Asian patients. Methods: Video endoscopy clips were selected from 45 consecutive patients participating in reflux studies. The videos were viewed by endoscopists who then independently scored the presence, severity and distribution of esophagitis, including endoscopically suspected Barrett's esophagus (ESBE). Each video was discussed and a consensus on findings reached. Kappa (k) correlation was calculated to describe inter-observer agreement. Results: Thirty-five clips were scored (no esophagitis 20%, grade-A 54%, grade-B 23%, grade-C 3%, respectively and 10 clips were excluded for poor imaging). Excellent agreement was noted on the presence of esophagitis (mean k = 0.79, range 0.77–0.82). Fifteen patients (42%) had ESBE with a mean k of 0.48 (range 0.39–0.60). Inter-observer agreement on the LA grade was good (mean k = 0.58, range 0.55–0.63), whilst in agreement between endoscopists and consensus grading, the mean kappa rose to 0.77 (range 0.73–0.81). There was a trend of increasing agreement as viewings progressed, with superior kappa correlation after 16 cases. Evaluation of the extent of esophagitis showed good k values using the alternative approach of grouping by circumferential extent (mean k = 0.64, range 0.60–0.67) at the lower categories of severity. Conclusions: Scoring using the LA classification for esophagitis and the concurrence on the presence of ESBE showed moderate to strong agreement amongst Asian endoscopists. Our results also suggested that an alternative method of scoring esophagitis based on proportion of circumferential involvement was reliable. A learning effect was observed and reliable scoring was achieved after 16 patients.

Background A 48-year-old Chinese woman presented with a 2-month history of progressive dysphagia for solids, and (less frequently) liquids. She had minimal weight loss and no family history of cancer. Investigations Physical examination, conventional esophagogastroduodenoscopy, CT, fluorodeoxyglucose–PET, endoscopic ultrasonography, and histopathologic examination of excised tumor and biopsy specimens. Diagnosis Primary malignant esophageal melanoma with submucosal infiltration but no distant metastasis. Management Endoscopic polypectomy followed by near-total esophagectomy with esophagogastric anastomosis.

We report a novel simultaneous fingerprint (FP) and high-wavenumber (HW) fiber-optic Raman spectroscopy developed for in vivo diagnosis of intestinal metaplasia (IM) in the stomach under wide-field endoscopic imaging. The FP/HW Raman endoscopy technique was performed to differentiate IM from normal tissues with sensitivity of 89% and specificity of 83%. This study shows the great potential of the FP/HW Raman endoscopic technique for early diagnosis of non-neoplastic gastric disease in vivo during routine endoscopic examination.

Background Transbronchial needle aspiration (TBNA) and EUS-guided FNA (EUS-FNA) are minimally invasive diagnostic approaches to mediastinal lymphadenopathy. Rapid on-site cytopathologic evaluation (ROSE) may facilitate the decision whether to proceed to a second procedure in the same session. The aim of this study was to determine the utility of TBNA with ROSE, combined with the option for immediate EUS-FNA in a single-session approach to mediastinal lymphadenopathy. Methods We prospectively recruited 20 patients (12 men; mean age 66.7 ± 10.2 years) with mediastinal lymphadenopathy on CT who required cytopathologic evaluation. Bronchoscopy was first performed with TBNA and ROSE. If this was unrevealing, EUS-FNA was performed immediately afterward with ROSE. All procedures were performed with the patient under local anesthesia and sedation. Results TBNA specimens were deemed adequate on-site in 13 patients, and EUS-FNA was performed in the remaining 7 patients. TBNA with ROSE was falsely negative in one patient. The diagnostic yield for TBNA and EUS-FNA alone was 65% and 86%, respectively. This single-session approach provided a yield of 90%, with no complications. The final diagnoses were 12 non-small-cell lung cancer, two small-cell lung cancer, one metastatic adenocarcinoma, two sarcoidosis, one tuberculosis, one lymphoma, and one with no definitive diagnosis. Conclusions Combining TBNA with the option for EUS-FNA immediately after unrevealing TBNA gave a yield approaching that of mediastinoscopy and, therefore, may reduce the need for invasive mediastinal sampling. This single-session endoscopic approach was safe, required only local anesthesia and sedation, was convenient, and obviated the need for patients to return for a second procedure.

Objective: The advent and utility of new endoscopic imaging modalities for predicting the histology of Barrett’s esophagus (BE) in real time with high accuracy appear promising and could potentially obviate the need to perform random biopsies where guidelines are poorly adhered to. We embarked on evaluating the performance characteristics of white-light endoscopy with magnification (WLE-z), narrow-band imaging with magnification (NBI-z) and a combination of both modalities. Design: This was a prospective online study with 28 endoscopists from 11 countries (Asia-Pacific region) participating as assessors. In total, 35 patients with BE were assessed using 150 slides from WLE-z and NBI-z randomly arranged using a simple classification with corresponding histology. The overall Accuracy (Acc), Sensitivity (Sn), Specificity (Sp), Positive Predictive Value (PPV), and Negative Predictive Value (NPV) of WLE-z, NBI-z and a combination of both were calculated. Results: The overall Acc for WLE-z and NBI-z images was 87.1 % and 88.7 %, respectively. When images from the two modalities were placed side by side, the Acc increased to 90.3 %. The Sn, Sp, PPV, and NPV of WLE-z were 48 %, 92 %, 45 %, and 93 % while with NBI-z, these improved to 89 %, 89 %, 56 %, and 98 %, respectively. When both imaging modalities were viewed together, they improved further to 93 %, 90 %, 61 %, and 99 %. Conclusion: The high NPV (99 %) when both WLE-z and NBI-z were used simultaneously indicates that areas with regular appearance that are diagnosed with confidence can effectively be left alone and not biopsied when performed at a skilled resourced center. This approach could potentially lead to a paradigm shift of how patients with BE are assessed.

Stem cells of the gastrointestinal tract, pancreas, liver and other columnar epithelia collectively resist cloning in their elemental states. Here we demonstrate the cloning and propagation of highly clonogenic, 'ground state' stem cells of the human intestine and colon. We show that derived stem-cell pedigrees sustain limited copy number and sequence variation despite extensive serial passaging and display exquisitely precise, cell-autonomous commitment to epithelial differentiation consistent with their origins along the intestinal tract. This developmentally patterned and epigenetically maintained commitment of stem cells is likely to enforce the functional specificity of the adult intestinal tract. Using clonally derived colonic epithelia, we show that toxins A or B of the enteric pathogen Clostridium difficile recapitulate the salient features of pseudomembranous colitis. The stability of the epigenetic commitment programs of these stem cells, coupled with their unlimited replicative expansion and maintained clonogenicity, suggests certain advantages for their use in disease modelling and regenerative medicine.

Background: This study aimed to describe the clinical features, manometric findings, prevalence and incidence of achalasia in Singapore. Methods: A total of 615 new patients referred for oesophageal manometry between 1989 and 1996 were examined prospectively. Twenty-four men and 25 women fulfilled the manometric and clinical criteria for achalasia. Results: Their median age of onset of symptoms was 37 years (range 15-71) and 37% first developed symptoms after the age of 50 years. The presenting symptoms were dysphagia (100%), regurgitation (80%), weight loss (67%) and chest discomfort (33%). Five patients (10%) had a history of benign (mostly autoimmune) thyroid disorders. Endoscopy was reported as normal in 10/43 patients (23%) and achalasia was suggested in only 31 (72%) of 43 barium examinations. Lower oesophageal sphincter (LOS) dysfunction was present in 82% of cases. Using data from medical records and from a survey of gastroenterologists and surgeons in Singapore, the prevalence (in 1996) and incidence of achalasia in Singapore were estimated to be 1.8 per 100 000, and 0.3 per 100 000 per year, respectively. The incidence was significantly lower in Malays than Chinese or Indians. The age-specific incidence of achalasia for both genders followed a bimodal distribution with the larger peak in the sixth decade. No cases of oesophageal carcinoma were identified among these patients. Conclusion: Achalasia is an uncommon condition in Singapore. The clinical and manometric features were similar to those described in Western countries.

Raman spectroscopy is a vibrational analytic technique sensitive to the changes in biomolecular composition and conformations occurring in tissue. With our most recent development of depth-resolved near-infrared (NIR) Raman endoscopy integrated with on-line diagnostic algorithms, in vivo real-time epithelial diagnostics has been realized under multimodal wide-field imaging (i.e., white- light reflectance (WLR), narrow-band imaging (NBI), autofluorescence imaging (AFI)) modalities. A selection of 43 patients who previously underwent Raman endoscopy (n=146 spectra) was used to render a robust model based on partial least squares - discriminant analysis (PLS-DA) for diagnosis of dysplasia in Barrett’s esophagus. The Raman endoscopy technique was validated prospectively on 2 new esophageal patients for in vivo tissue diagnosis. The Raman endoscopic technique could identify esophageal high-grade dysplasia in vivo with an accuracy of 85.9% (sensitivity: 91.3% (21/23): specificity 83.3% (40/48)) on spectrum basis. This study realizes for the first time depth-resolved Raman endoscopy for real-time in vivo diagnosis of dysplasia in Barrett’s epithelium at the biomolecular level.

Background: Linear endoscopic ultrasound (EUS) evaluation of pancreaticobiliary (PB) system usually requires scanning from both stomach and duodenum. Feasibility of assessing the complete PB system from stomach alone has not been studied. Objectives: To conceptualize and evaluate a system-based approach (railroad approach) for linear PB-EUS, by which the PB anatomy could be assessed from the stomach itself. Methods: Three maneuvers were conceptualized and evaluated (alpha maneuver for stomach and sigma and xi maneuvers for duodenum). The maneuvers were prospectively evaluated in 100 consecutive patients requiring PB-EUS. Results: The three maneuvers could be completed in a median time of 12 min (range 8-22 min). Median total procedure time was significantly higher than that for alpha maneuver alone (12 vs. 6 min, P = 0.0001). The visualization rates of hilum and common hepatic duct (100% vs. 83.5%, P = 0.0001) were significantly higher from the stomach than from the duodenum. The visualization rates of retropancreatic common bile duct (CBD) (97.6% vs. 100%, P = 0.49), uncinate process (100% vs. 100%), and pancreatic duct (98.8% vs. 100%, P = 1.0) did not differ significantly if patients with pancreatic head calcifications were excluded. There was no significant difference in the clinical diagnosis made from the stomach versus that made from the duodenum, after excluding body and tail lesions (head of the pancreas neoplasms 100% vs. 100%, CBD stone 100% vs. 84.6% [P = 0.75], pancreatic cysts 83.3% vs. 83.3%, respectively). Conclusions: Adequate anatomical and diagnostic information of the PB system may be acquired by EUS scanning from the stomach in significantly shorter procedure time.

Background: Endoscopic ultrasound-guided biliary drainage (EUS-BD) is an acceptable rescue option in patients with failed endoscopic retrograde cholangiopancreatography (ERCP). EUS-guided biliary rendezvous (EUS-RV) allows transpapillary drainage in patients with failed ERCP and approachable papilla. There are limited learning and training opportunities for EUS-guided biliary drainage (EUS-BD) and EUS-RV at most centers due to low case volumes. An effective and easily reproducible model is desirable Objectives: To develop and validate a model for stepwise learning of EUS-BD and EUS-RV. Methods: A hybrid model was created utilizing pig esophagus and stomach, synthetic duodenum, and synthetic biliary system with distal stricture. Twenty-eight trainees were given hands-on training in EUS-BD and EUS-RV procedures. They were assessed for objective criteria (needle puncture, contrast injection, and guidewire manipulation across hilar bifurcation, stricture, and papilla, followed by guidewire retrieval with snare into the duodenoscope channel and stent placement). Results: All trainees could complete the requisite steps of EUS-BD and EUS-RV in a mean time of 11 min (8–18 min). Twenty trainees had technical issues during the procedures, which were corrected by the expert (wrong scope position 4, incorrect duct puncture 8, guidewire manipulation 8). At 10 days follow-up, 9 of 28 trainees had successfully performed three EUS-RV and seven EUS-BD procedures independently at their respective institutes. Conclusions: The Mumbai EUS II hybrid model gives real-life feel of situations encountered during EUS-RV and EUS-BD.

Raman spectroscopy is a vibrational analytic technique sensitive to the changes in biomolecular composition and conformations occurring in tissue. With our most recent development of near-infrared (NIR) Raman endoscopy integrated with diagnostic algorithms, in vivo real-time Raman diagnostics has been realized under multimodal wide-field imaging (i.e., white- light reflectance (WLR), narrow-band imaging (NBI), autofluorescence imaging (AFI)) modalities. A selection of 177 patients who previously underwent Raman endoscopy (n=2510 spectra) was used to render two robust models based on partial least squares - discriminant analysis (PLS-DA) for esophageal and gastric cancer diagnosis. The Raman endoscopy technique was validated prospectively on 4 new gastric and esophageal patients for in vivo tissue diagnosis. The Raman endoscopic technique could identify esophageal cancer in vivo with a sensitivity of 88.9% (8/9) and specificity of 100.0% (11/11) and gastric cancers with a sensitivity of 77.8% (14/18) and specificity of 100.0% (13/13). This study realizes for the first time the image-guided Raman endoscopy for real-time in vivo diagnosis of malignancies in the esophagus and gastric at the biomolecular level.

The aim of this work was to evaluate the biochemical foundation and clinical merit of multimodal image-guided Raman endoscopy technique for real-time in vivo diagnosis of cancer in the esophagus during clinical endoscopic examinations. A novel fiber-optic Raman endoscopy system was utilized for in vivo esophageal Raman measurements at 785 nm laser excitation within 0.5 second under the multimodal wide-field endoscopic imaging (white light reflectance (WLR) imaging, narrow-band imaging (NBI) and autofluorescence imaging (AFI) guidance. A total of 75 esophageal tissue sites from 27 patients were measured, in which 42 in vivo Raman spectra were from normal tissues and 33 in vivo Raman spectra were from malignant tumors as confirmed by histopathology. The biomolecular modeling (non-negativity-constrained least-squares minimization (NNCLSM) utilizing six basis reference spectra from the representative biochemicals ( i.e., actin, collagen, DNA, histones, triolein and glycogen) were employed to estimate the biochemical compositions of esophageal tissue. The resulting diagnostically significant fit coefficients were further utilized through linear discriminant analysis (LDA) and leave-one tissue site-out, cross validation method to develop diagnostic algorithms for esophageal cancer diagnosis. High-quality in vivo Raman spectra in the range of 800–1800 cm−1 can be acquired from normal and cancerous esophageal mucosa in real-time under multimodal endoscopic imaging guidance. Esophageal cancer tissue showed distinct Raman signals mainly associated with cell proliferation, lipid reduction, abnormal nuclear activity and neovasculation. The fit coefficients for actin, DNA, histones, triolein, and glycogen were found to be most significant for construction of the LDA diagnostic model, giving rise to an accuracy of 96.0% ( i.e., sensitivity of 97.0% and specificity of 95.2%) for in vivo diagnosis of esophageal cancer. This study demonstrates that multimodal image-guided Raman endoscopy technique in conjunction with biomolecular modeling has promising potential for the real-time, in vivo diagnosis and detection of esophageal cancer during clinical endoscopic examination.

Confocal laser endomicroscopy (CLE) may be used to diagnose gastric cancer and intestinal metaplasia, but the impact of CLE experience on the accuracy of confocal diagnosis of gastric cancer and intestinal metaplasia is not clear.To establish the sensitivity, specificity, and intragroup interobserver agreement of CLE image interpretation by 3 experienced (group 1) and 3 inexperienced (group 2) CLE endoscopists for diagnosing gastric intestinal metaplasia (GIM) and adenocarcinoma.Blinded review of CLE images for the diagnosis of gastric cancer or intestinal metaplasia.Tertiary care hospital.CLE images obtained ex vivo from gastrectomy specimens with proven gastric cancer and CLE images obtained in vivo from Chinese subjects older than 50 years of age by using matched biopsy specimens as reference standards.Sensitivity, specificity, and intragroup interobserver agreement of CLE image interpretation.Interpretation of in vivo images by group 1 was associated with higher sensitivity (95.2% vs 61.9%, P = .039) and higher specificity (93.3% vs 62.2%, P.001) for GIM than interpretation by group 2. The agreement between interpretation by group 1 and histology for GIM was higher than that for group 2 (κ = 0.864 vs 0.217). The sensitivity (93.3% for group 1 vs 86.7% for group 2, P = 1.000) and specificity (87.7% for group 1 vs 80.7% for group 2, P = .344) of interpretation of ex vivo CLE images for the diagnosis of gastric adenocarcinoma was similar for groups 1 and 2.Single-center study.Experience in CLE was associated with greater accuracy in the diagnosis of intestinal metaplasia.

The aim of this study was to evaluate the clinical utility of an image-guided Raman endoscopy technique for in vivo differential diagnosis of benign and malignant ulcerous lesions in the stomach. A rapid-acquisition image-guided Raman endoscopy system with 785 nm laser excitation has been developed to acquire in vivo gastric tissue Raman spectra within 0.5 s during clinical gastroscopic examinations. A total of 1102 in vivo Raman spectra were acquired from 71 gastric patients, in which 924 Raman spectra were from normal tissue, 111 Raman spectra were from benign ulcers whereas 67 Raman spectra were from ulcerated adenocarcinoma. There were distinctive spectral differences in Raman spectra among normal mucosa, benign ulcers and malignant ulcers, particularly in the spectral ranges of 800-900, 1000-1100, 1245-1335, 1440-1450 and 1500-1800 cm(-1), which primarily contain signals related to proteins, DNA, lipids and blood. The malignant ulcerous lesions showed Raman signals to be mainly associated with abnormal nuclear activity and decrease in lipids as compared to benign ulcers. Partial least squares-discriminant analysis (PLS-DA) was employed to generate multi-class diagnostic algorithms for classification of Raman spectra of different gastric tissue types. The PLS-DA algorithms together with leave-one tissue site-out, cross validation technique yielded diagnostic sensitivities of 90.8%, 84.7%, 82.1%, and specificities of 93.8%, 94.5%, 95.3%, respectively, for classification of normal mucosa, benign and malignant ulcerous lesions in the stomach. This work demonstrates that image-guided Raman endoscopy technique associated with PLS-DA diagnostic algorithms has for the first time promising clinical potential for rapid, in vivo diagnosis and detection of malignant ulcerous gastric lesions at the molecular level.

The establishment of precise and valid diagnostic criteria is important for any disease. We determined the interobserver reliability in the endoscopic diagnosis and grading of Barrett's esophagus.Video clips of endoscopy in 21 patients with/without Barrett's esophagus were used for training (n = 3) and for diagnosis/grading (n = 18) of Barrett's esophagus by endoscopists from seven hospitals in Asia. Barrett's esophagus was graded using the Prague CM Criteria whereby the circumferential extent of the Barrett's segment (C value), maximum extent of Barrett's segment (M value), location of the gastroesophageal junction, and location of the diaphragmatic hiatus were scored. The intraclass correlation coefficients (ICC) were calculated as a measure of interobserver reliability.A total of 34 endoscopists participated. ICC values for the scores of the C value, M value, location of the gastroesophageal junction, and location of the diaphragmatic hiatus were: 0.92 (95 % confidence interval [CI] 0.88 - 0.97), 0.94 (95 %CI 0.90 - 0.98), 0.86 (95 %CI 0.78 - 0.94), and 0.81 (95 %CI 0.71 - 0.92), respectively, indicating excellent interobserver agreement. The differences in region/country, endoscopists' experience, case volume of participating centers, or primary practice type had no significant effect on the reliability. The ICC values for recognition of Barrett's esophagus ofor = 1 cm were 0.90 (95 %CI 0.80 - 1.00) and 0.92 (95 %CI 0.87 - 0.98) for the C and M values, respectively, whereas the corresponding ICC values for Barrett's segment of1 cm were 0.18 (95 %CI 0.03 - 0.32) and 0.21 (95 %CI 0.00 - 0.51), respectively.Despite the uncommon occurrence of Barrett's esophagus in Asia, our endoscopists exhibited excellent agreement in the endoscopic diagnosis and grading of Barrett's esophagus using the Prague CM Criteria. However, in view of the low interobserver reliability in recognizing Barrett's segments of1 cm, future studies in Asia should take this into account when selecting the study population.