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BACKGROUND Gamma-glutamyl transferase (GGT) is associated with the risk of cardiovascular disease (CVD) in the general population. AIM To identify the association of baseline GGT level and QRISK2 score among patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD). METHODS This was a retrospective study involving 1535 biopsy-proven NAFLD patients from 10 Asian centers in 8 countries using data collected by the Gut and Obesity in Asia (referred to as "GO ASIA") workgroup. All patients with available baseline GGT levels and all 16 variables for the QRISK2 calculation (QRISK2-2017; developed by researchers at the United Kingdom National Health Service; https://qrisk.org/2017/; 10-year cardiovascular risk estimation) were included and compared to healthy controls with the same age, sex, and ethnicity. Relative risk was reported. QRISK2 score > 10% was defined as the high-CVD-risk group. Fibrosis stages 3 and 4 (F3 and F4) were considered advanced fibrosis. RESULTS A total of 1122 patients (73%) had complete data and were included in the final analysis; 314 (28%) had advanced fibrosis. The median age (interquartile range [IQR]) of the study population was 53 (44-60) years, 532 (47.4%) were females, and 492 (43.9%) were of Chinese ethnicity. The median 10-year CVD risk (IQR) was 5.9% (2.6-10.9), and the median relative risk of CVD over 10 years (IQR) was 1.65 (1.13-2.2) compared to healthy individuals with the same age, sex, and ethnicity. The high-CVD-risk group was significantly older than the low-risk group (median [IQR]: 63 [59-67] vs 49 [41-55] years; P < 0.001). Higher fibrosis stages in biopsy-proven NAFLD patients brought a significantly higher CVD risk (P < 0.001). Median GGT level was not different between the two groups (GGT [U/L]: Median [IQR], high risk 60 [37-113] vs low risk 66 [38-103], P = 0.56). There was no correlation between baseline GGT level and 10-year CVD risk based on the QRISK2 score (r = 0.02). CONCLUSION The CVD risk of NAFLD patients is higher than that of healthy individuals. Baseline GGT level cannot predict CVD risk in NAFLD patients. However, advanced fibrosis is a predictor of a high CVD risk.

Intragastric balloons (IGBs), by occupying the stomach space and prolonging satiety, is a promising method to treat obesity and consequently improves its associated comorbidities, e.g. coronary heart disease, diabetes, and cancer. However, existing IGBs are often tethered with tubes for gas or liquid delivery or require endoscopic assistance for device delivery or removal, which are usually uncomfortable, costly, and may cause complications. This paper presents a novel tetherless, magnetically actuated capsule (EndoPil) which can deploy an IGB inside the stomach after being swallowed and being activated by an external magnet. The external magnet attracts a small magnet inside the EndoPil to open a valve, triggering the chemical reaction of citric acid and potassium bicarbonate to produce carbon dioxide gas, which inflates a biocompatible balloon (around 120 mL). A prototype, 13 mm in diameter and 35 mm in length, was developed. Simulations and bench-top tests were conducted to test the force capability of the magnetic actuation mechanism, the required force to activate the valve, and the repeatability of balloon inflation. Experiments on animal and human were successfully conducted to demonstrate the safety and feasibility of inflating a balloon inside the stomach by an external magnet. Nanyang Technological University The study is funded by the Gastroenterology Research Fund in Singapore (NUS WBS No. R-172-000-004-720) and the Startup Grant from Nanyang Technological University, Singapore (NTU WBS No. M4081419).

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.

A significant proportion of the non-alcoholic fatty liver disease (NAFLD) population is non-obese. Prior studies reporting the severity of NAFLD amongst non-obese patients were heterogenous. Our study, using data from the largest biopsy-proven NAFLD international registry within Asia, aims to characterize the demographic, metabolic and histological differences between non-obese and obese NAFLD patients.1812 biopsy-proven NAFLD patients across nine countries in Asia assessed between 2006 and 2019 were pooled into a curated clinical registry. Demographic, metabolic and histological differences between non-obese and obese NAFLD patients were evaluated. The performance of Fibrosis-4 index for liver fibrosis (FIB-4) and NAFLD fibrosis score (NFS) to identify advanced liver disease across the varying obesity subgroups was compared. A random forest analysis was performed to identify novel predictors of fibrosis and steatohepatitis in non-obese patients.One-fifth (21.6%) of NAFLD patients were non-obese. Non-obese NAFLD patients had lower proportions of NASH (50.5% vs 56.5%, p = 0.033) and advanced fibrosis (14.0% vs 18.7%, p = 0.033). Metabolic syndrome in non-obese individuals was associated with NASH (OR 1.59, 95% CI 1.01-2.54, p = 0.047) and advanced fibrosis (OR 1.88, 95% CI 0.99-3.54, p = 0.051). FIB-4 performed better than the NFS score (AUROC 81.5% vs 73.7%, p 0.001) when classifying patients with F2-4 fibrosis amongst non-obese NAFLD patients. Haemoglobin, GGT, waist circumference and cholesterol are additional variables found on random forest analysis useful for identifying non-obese NAFLD patients with advanced liver disease.A substantial proportion of non-obese NAFLD patients has NASH or advanced fibrosis. FIB-4, compared to NFS better identifies non-obese NAFLD patients with advanced liver disease. Serum GGT, cholesterol, haemoglobin and waist circumference, which are neither components of NFS nor FIB-4, are important biomarkers for advanced liver disease in non-obese patients.

BACKGROUND The Gut and Obesity Asia (GO ASIA) workgroup was formed to study the relationships between obesity and gastrointestinal diseases in the Asia Pacific region. AIM To study factors associated with nonalcoholic steatohepatitis (NASH) and advanced fibrosis, and medical treatment of biopsy-proven nonalcoholic fatty liver disease (NAFLD) patients. METHODS Retrospective study of biopsy-proven NAFLD patients from centres in the GO ASIA Workgroup. Independent factors associated with NASH and with advanced fibrosis on binary logistic regression analyses in a training cohort were used for the development of their corresponding risk score, which were validated in a validation cohort. RESULTS We included 1008 patients from nine centres across eight countries (NASH 62.9%, advanced fibrosis 17.2%). Independent predictors of NASH were body mass index ≥30 kg/m2 , diabetes mellitus, dyslipidaemia, alanine aminotransferase ≥88 U/L and aspartate aminotransferase ≥38 U/L, constituting the Asia Pacific NASH risk score. A high score has a positive predictive value of 80%-83% for NASH. Independent predictors of advanced fibrosis were age ≥55 years, diabetes mellitus and platelet count

Background The Gut and Obesity in Asia (GOASIA) Workgroup was formed to study obesity and gastrointestinal diseases in the Asia Pacific region. We aimed to 1) compare the characteristics of elderly (i.e. age ≥ 60) vs. non-elderly patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD); 2) identify predictors of advanced fibrosis in elderly patients with NAFLD; and 3) assess the performance of non-invasive fibrosis scores in the prediction of advance fibrosis in the elderly population. Methods We abstracted the data of 1008 patients with NAFLD from nine centers across eight countries. Characteristics of elderly and non-elderly patients with NAFLD were compared using 1:3 sex-matched analysis. Results Of the 1008 patients, 175 were elderly [age 64 (62–67) years], who were matched with 525 non-elderly patients [46 (36–54) years]. Elderly patients were more likely to have advanced fibrosis (35.4% vs. 13.3%; p Conclusions Elderly patients with NAFLD had a higher prevalence of advanced fibrosis than non-elderly patients. Female and hypertension were predicting factors for advanced fibrosis in the elderly. Non-invasive fibrosis scores had a lower specificity in elderly.

Objective Intestinal metaplasia (IM) is a premalignant stage that poses a greater risk for subsequent gastric cancer (GC). However, factors regulating IM to GC progression remain unclear. Previously, activated DNA damage response (DDR) signalling factors were shown to engage tumour-suppressive networks in premalignant lesions. Here, we interrogate the relationship of DDR signalling to mutational accumulation in IM lesions. Design IM biopsies were procured from the gastric cancer epidemiology programme, an endoscopic surveillance programme where biopsies have been subjected to (epi)genomic characterisation. IM samples were classified as genome-stable or genome-unstable based on their mutational burden/somatic copy-number alteration (CNA) profiles. Samples were probed for DDR signalling and cell proliferation, using the markers γH2AX and MCM2, respectively. The expression of the gastric stem cell marker, CD44v9, was also assessed. Tissue microarrays representing the GC progression spectrum were included. Results MCM2-positivity increased during GC progression, while γH2AX-positivity showed modest increase from normal to gastritis and IM stages, with further increase in GC. γH2AX levels correlated with the extent of chronic inflammation. Interestingly, genome-stable IM lesions had higher γH2AX levels underscoring a protective anti-cancer role for DDR signalling. In contrast, genome-unstable IM lesions with higher mutational burden/CNAs had lower γH2AX levels, elevated CD44v9 expression and modest promoter hypermethylation of DNA repair genes WRN, MLH1 and RAD52. Conclusions Our data suggest that IM lesions with active DDR will likely experience a longer latency at the premalignant state until additional hits that override DDR signalling clonally expand and promote progression. These observations provide insights on the factors governing IM progression.

We report a unique simultaneous fingerprint (FP) and high-wavenumber (HW) Raman spectroscopy technique coupled with a beveled fiber-optic Raman probe for improving in vivo detection of gastric intestinal metaplasia (IM)–precancerous lesions in real-time during clinical gastroscopy. A total of 4,520 high-quality in vivo FP/HW gastric Raman spectra (normal = 4,178; IM = 342) were acquired from 157 gastric patients undergoing endoscopic examination. Multivariate diagnostic algorithms based on principal components analysis and linear discriminant analysis together with the leave-one tissue site-out, cross-validation on in vivo tissue Raman spectra yield the diagnostic sensitivities of 89.3%, 89.3%, and 75.0%; specificities of 92.2%, 84.4%, and 82.0%; positive predictive values of 52.1%, 35.2%, and 28.4%; and negative predictive values of 98.9%, 98.8%, and 97.2%, respectively, by using the integrated FP/HW, FP, and HW Raman techniques for identifying IM from normal gastric tissue. Further, ROC curves generated show that the integrated FP/HW Raman technique gives the integration area under the ROC curve of 0.92 for IM classification, which is superior to either FP (0.89) or HW Raman (0.86) technique alone. This work demonstrates for the first time that the simultaneous FP/HW fiber-optic Raman spectroscopy has great potential to enhance early diagnosis of gastric precancer in vivo during routine endoscopic examination. Cancer Prev Res; 9(6); 476–83. ©2016 AACR.

Background & Aims Measuring liver stiffness only in patients with indeterminate or high nonalcoholic fatty liver disease (NAFLD) fibrosis scores (called a 2-step approach) was reported to reduce indeterminate or discordant results while maintaining the accuracy to identify patients with advanced fibrosis. We aimed to validate this approach using data collected from the Gut and Obesity in Asia Workgroup. Methods We performed a retrospective analysis of data from 759 patients with biopsy-proven NAFLD (24% with advanced fibrosis), seen at 10 centers in 9 countries in Asia, from 2006 through 2018. By using liver biopsies as the reference standard, we calculated percentages of misclassifications and indeterminate or discordant results from assessments made based on fibrosis scores (NAFLD fibrosis score [NFS] or Fibrosis-4 score) and liver stiffness measurements (LSMs), alone or in combination. The analysis was repeated using randomly selected subgroups with a different prevalence of advanced fibrosis (histologic fibrosis stage ≥F3). Results In groups in which 3.7% and 10% of patients had advanced fibrosis, a 2-step approach (using the NFS followed by LSM only for patients with indeterminate or high NFS) and using a gray zone of 10 to 15 kPa for LSM, produced indeterminate or discordant results for 6.9% of patients and misclassified 2.7% of patients; only 25.6% of patients required LSM. In the group in which 10% of patients had advanced fibrosis, the same approach produced indeterminate or discordant results for 7.9% of patients and misclassified 6.6% of patients; only 27.4% of patients required LSM. In groups in which 24% and 50% of patients had advanced fibrosis, using LSM ≥10 kPa alone for the diagnosis of advanced fibrosis had the highest accuracy and misclassified 18.1% and 18.3% of patients, respectively. These results were similar when the Fibrosis-4 score was used in place of NFS. Conclusions In a retrospective analysis, we found that a 2-step approach using fibrosis scores followed by LSM most accurately detects advanced fibrosis in populations with a low prevalence of advanced fibrosis. However, LSM ≥10 kPa identifies patients with advanced fibrosis with the highest level of accuracy in populations with a high prevalence of advanced fibrosis.

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.

Background Barrett's oesophagus is a premalignant condition, predisposing to oesophageal adenocarcinoma. However, some adenocarcinoma may arise in columnar lined oesophagus without goblet cells. Our aim was to evaluate the biological properties of non-goblet columnar lined oesophagus only and elucidate its relationship with Barrett's oesophagus and associated neoplasia. Methods Endoscopic biopsies from patients with Barrett's oesophagus ( n = 30), non-goblet columnar lined oesophagus ( n = 14), Barrett's oesophagus associated high grade dysplasia ( n = 6) and adenocarcinoma ( n = 4) were selected. Immunostaining for villin, claudin 3 and MUC4 was performed. Statistical analysis was performed and a p value Results Villin and MUC4 were positive in 42%, 100% each and 50% in non-goblet columnar lined oesophagus, Barrett's oesophagus, high grade dysplasia and adenocarcinoma respectively, while claudin 3 was 100% positive in all the groups. In non-goblet columnar lined oesophagus, six cases that were villin immunopositive, showed positive expression for claudin 3 and/or MUC4 and there was no difference from the high grade dysplasia or adenocarcinoma ( p > 0.05). Conclusion Our results indicate that a subset of non-goblet columnar lined oesophagus shows an intestinal phenotype representing an early stage of Barrett's oesophagus. This subset probably harbours the potential to change into adenocarcinoma in the long term.

Background Endogenous pain modulation (EPM) is central to the processing of sensory information. Visceral and somatic EPM are abnormal in irritable bowel syndrome, but have not been studied in functional dyspepsia (FD). Methods Visceral EPM was assessed in 34 FD patients and 42 healthy controls. Gastric pain was induced with oral capsaicin and EPM was studied by adding heterotopic thermal foot stimulation or distraction by STROOP test. Somatic EPM was assessed using foot heat stimulation with heterotopic hand electrical stimulation. Key Results Endogenous pain modulation by distraction reduced mean gastric pain by 11.9 on the 0–100 visual analog scale (95% CI: 3.8–20.1) in controls (p = 0.006) and by 2.0 (−6.18 to 10.44) in FD (p = 0.6), with greater EPM in controls than in FD (difference −13.3 [−26.1 to −0.5]; p = 0.04). Endogenous pain modulation by heterotopic foot stimulation reduced gastric pain by 6.5 (−0.7 to 13.6) in controls (p = 0.07) and by 7.1 (−2.29 to 16.47) in FD (p = 0.1), with no significant difference in EPM between controls and FD (−2.0 [−14.5 to 10.5]; p = 0.75). In patients with prominent FD pain, greater pain correlated with decreased visceral EPM by distraction (r = 0.51, p = 0.04). Somatic EPM by heterotopic stimulation significantly decreased foot pain in controls (p = 0.004), but not in FD (p = 0.80). Conclusions & Inferences In FD, visceral pain modulation by distraction was dysfunctional compared to controls. Somatic pain modulation was also decreased in FD. These data and the correlation of abnormal pain modulation by distraction with clinical pain in pain-predominant FD suggest a potential pathophysiological significance of abnormal pain modulation in FD.

We prospectively compared the diagnostic performance of autofluorescence imaging (AFI), magnifying narrow band imaging (mNBI), and probe-based confocal laser endomicroscopy (pCLE) with white light endoscopy (WLE) for the diagnosis of gastric intestinal metaplasia (GIM), using histology as the “gold standard.” Chinese >50 years old with history of GIM were prospectively recruited. All subjects underwent WLE, followed by AFI and NBI, and finally pCLE. Patients were randomized to undergo either AFI before NBI or vice versa. In each patient, a minimum of six sites (antrum lesser and greater curve, body lesser and greater curve, incisura, cardia, and any lesion) were each examined by WLE, AFI, NBI, and pCLE. The diagnoses were made real-time. Biopsies for histology were taken from all examined sites. pCLE videos also were reviewed off-site. Analysis was performed per-site. A total of 125 sites in 20 patients were examined. For diagnosing GIM, real-time pCLE had better sensitivity (90.9 vs. 37.9 %, p

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 There is no satisfactory treatment for nonalcoholic steatohepatitis (NASH). The Bioenterics intragastric balloon (BIB) can be an effective treatment for weight reduction in obese patients. Objective We evaluated the efficacy of the BIB in improving the histology of NASH in obese patients. Design Randomized, controlled study. Setting University hospital. Patients Obese patients with body mass indexes (BMI) ≥27 kg/m 2 and who had histologic evidence of NASH were recruited. Intervention Patients were randomly assigned to a step 1 American Heart Association (AHA) diet plus exercise and BIB placement or step 1 AHA diet plus exercise and sham BIB placement for a period of 6 months. Main Outcome Measurements Liver histology was the primary outcome measure recorded before and after treatment. Results A total of 18 patients completed the study. Baseline characteristics of the BIB and sham groups were similar. At 6 months, a significant reduction in the mean BMI was seen in the BIB group (1.52 vs 0.8; P = .0008). The median nonalcoholic fatty liver disease activity scores at the end of treatment were significantly lower in the BIB-treated compared with the sham-treated groups (2 [0.75] vs 4 [2.25]; P = .03). There was a trend toward improvement in the median steatosis scores (1 [0.75] vs 1 [1]; P = .075). There was no change in the median loblular inflammation, hepatocellular ballooning, or fibrosis scores in both groups after treatment. Limitations Pilot study with small numbers and short duration. Conclusion Results from this pilot study demonstrated that addition of BIB for 6 months provided a greater loss of BMI and improvement in 2 of 5 histologic parameters of nonalcoholic fatty liver disease. A longer study with larger numbers will be required to prove whether or not the therapy is meaningful in the treatment of NASH.

There are limited data on the effect of curry on gastroesophageal reflux disease (GERD). Our objective was to study the effects of curry on GERD.Symptomatic non-erosive gastroesophageal reflux disease (NERD) patients and healthy volunteers underwent ambulatory 24-h esophageal pH monitoring before consumption of either 400 or 800 ml of curry; they were monitored for 3 h thereafter for changes in esophageal pH and upper abdominal symptoms. Selected volunteers were monitored similarly after water ingestion.In total, 25 NERD patients (23 males; mean age, 45 years) and 19 volunteers (13 males; mean age, 22 years) participated. In both patients and volunteers, curry ingestion induced more esophageal acid exposure than did ingestion of a similar volume of water. Curry induced significantly more esophageal acid exposure in NERD patients than in volunteers. Upper abdominal symptoms and esophageal acid exposure were more severe and persisted longer in patients than in volunteers.Curry induced more acid reflux and caused worse symptoms in patients with NERD than in healthy individuals. Patients with NERD should be advised to avoid curry ingestion.

Objective To develop and validate a clinical risk score predictive of risk for colorectal advanced neoplasia for Asia. Methods A prospective, cross-sectional and multicentre study was carried out in tertiary hospitals in 11 Asian cities. The subjects comprise 2752 asymptomatic patients undergoing screening colonoscopy. From a development set of 860 asymptomatic subjects undergoing screening colonoscopy, multiple logistic regression was applied to identify significant risk factors for advanced colorectal neoplasia defined as invasive carcinoma or advanced adenoma. The ORs for significant risk factors were utilised to develop a risk score ranging from 0 to 7 (Asia-Pacific Colorectal Screening (APCS) score). Three tiers of risk were arbitrarily defined: 0–1 ‘average risk’ (AR); 2–3 ‘moderate risk’ (MR); and 4–7 ‘high risk’ (HR). Subjects undergoing screening colonoscopy between July 2006 and December 2007 were prospectively enrolled to form an independent validation group. Each subject had a personal APCS score calculated by summing the points attributed from the presence of risk factors in the individuals. The performance of the APCS score in predicting risk of advanced neoplasia was evaluated. Results There were 860 subjects in the derivation set and 1892 subjects in the validation set, with a baseline prevalence of advanced neoplasia of 4.5% and 3%, respectively. Applying the APCS stratification in the validation set, 559 subjects (29.5%) were in the AR tier, 966 subjects (51.1%) in the MR tier and 367 (19.4%) subjects in the HR tier. The prevalence of advanced neoplasia in the AR, MR and HR groups was 1.3, 3.2 and 5.2%, respectively. The subjects in the MR and HR tiers had 2.6-fold (95% CI 1.1 to 6.0) and 4.3-fold (95% CI 1.8 to 10.3) increased prevalence of advanced neoplasia, respectively, than those in the AR tier. Conclusions The APCS score based on age, gender, family history and smoking is useful in selecting asymptomatic Asian subjects for priority of colorectal screening.

Background Confocal laser endomicroscopy (CLE) is a novel endoscopic modality that allows subsurface analysis of the gastric mucosa during ongoing endoscopy. Several studies have reported that this technique is of value in the diagnosis of premalignant lesions in the GI tract, but as yet no investigations have reported its application in the analysis of gastric intraepithelial neoplasia (GIN). Objective To assess the feasibility of CLE for the identification and grading of GIN. Design Prospective double-blind feasibility study. Setting Qilu Hospital, Shandong University, Jinan, China. Patients CLE images of 33 patients were first evaluated to establish the diagnostic criteria for gastric lesions. Eligible patients were then prospectively investigated by CLE using the newly established criteria. Interventions All endoscopically suspicious lesions were examined by CLE, and CLE diagnoses were compared with corresponding histopathologic results. Main Outcome Measurements Sensitivity, specificity, and positive and negative likelihood ratios of CLE diagnosis of biopsy-proven intraepithelial neoplasia by per-lesion analysis. Results The sensitivity, specificity, and positive and negative likelihood ratios of CLE diagnosis of GIN were 77.8%, 81.8%, 4.28, and 0.27, respectively. The mean κ value for interobserver agreement for the diagnosis of GIN was 0.70 among endoscopists and 0.71 between endoscopist and GI pathologist. Intraepithelial neoplasia score ≥5 differentiated high-grade from low-grade intraepithelial neoplasia with a sensitivity of 66.7% and a specificity of 88.0%. Limitations Nonrandomized single-center study, limited number of patients. Conclusions CLE is an acceptable and potentially useful technology for the identification and grading of GIN in vivo. The diagnostic accuracy needs to be improved.

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.

The lack of triangulation of standard endoscopic devices limits the degree of freedom for surgical maneuvers during natural orifice transluminal endoscopic surgery (NOTES). This study explored the feasibility of adapting an intuitively controlled master and slave transluminal endoscopic robot (MASTER) the authors developed to facilitate wedge hepatic resection in NOTES.The MASTER consists of a master controller, a telesurgical workstation, and a slave manipulator that holds two end-effectors: a grasper, and a monopolar electrocautery hook. The master controller is attached to the wrist and fingers of the operator and connected to the manipulator by electrical and wire cables. Movements of the operator are detected and converted into control signals driving the slave manipulator via a tendon-sheath power transmission mechanism allowing nine degrees of freedom. Using this system, wedge hepatic resection was performed through the transgastric route on two female pigs under general anesthesia. Entry into the peritoneal cavity was via a 10-mm incision made on the anterior wall of the stomach by the electrocautery hook. Wedge hepatic resection was performed using the robotic grasper and hook. Hemostasis was achieved with the electrocautery hook. After the procedure, the resected liver tissue was retrieved through the mouth using the grasper.Using the MASTER, transgastric wedge hepatic resection was successfully performed on two pigs with no laparoscopic assistance. The entire procedure took 9.4 min (range, 8.5-10.2 min), with 7.1 min (range, 6-8.2 min) spent on excision of the liver tissue. The robotics-controlled device was able to grasp, retract, and excise the liver specimen successfully in the desired plane.This study demonstrated for the first time that the MASTER could effectively mitigate the technical constraints normally encountered in NOTES procedures. With it, the triangulation of surgical tools and the manipulation of tissue became easy, and wedge hepatic resection could be accomplished successfully without the need for assistance using laparoscopic instruments.

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.

All sensory input underlies modulation by endogenous central nervous system pathways. Dysfunctional endogenous pain modulation has been demonstrated in central sensitization and in several pain syndromes, including Irritable Bowel Syndrome (IBS) Activation of endogenous visceral pain modulation by heterotopic stimulation was compared using different methods. Rectal electrical or distension pain alone or with simultaneous (i.e. heterotopic) noxious hand or foot cold stimulation were investigated in randomized sequence in 14 male and 1 female healthy subjects. Mean pain intensities on a visual analogue scale of 0-100 (95% CI) during tonic rectal electrical and distension stimulation alone were 64 (52-76) and 55 (39-71), respectively. Rectal distension pain decreased by 36% (18-55) with simultaneous hand and by 45% (24-66) with simultaneous foot cold pain. Rectal electrical pain decreased by 45% (29-61) during hand and by 46% (28-64) during foot cold pain. Facilitation, i.e. increased rectal pain during heterotopic stimulation was observed in only 1 of 60 stimulation runs. Potent and consistent activation of endogenous visceral pain inhibition was achieved with heterotopic cold pain limb stimulation. Somato-visceral convergence did not affect the effectiveness of induction of endogenous visceral pain inhibition in healthy subjects, as hand and foot heterotopic stimulation resulted in similar pain inhibition. Pain facilitation, as shown earlier in IBS patients, was not evident in healthy controls.

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.

Ilaprazole (IY-81149) is a new proton-pump inhibitor (PPI) not previously studied in human patients with ulcer disease. This study evaluated and compared it with a reference PPI, omeprazole, in the treatment of gastric and duodenal ulcers.This was a double-blind, parallel, randomized study. Patients aged 18 years and above with at least one endoscopically confirmed active non-malignant gastric/duodenal ulcer were treated with 20 mg/day omeprazole or 5 mg/day or 10 mg/day ilaprazole for four weeks. Healing of ulcer was determined by its resolution from active to scarring stage. Symptoms relief was evaluated using a graded score. Safety and tolerability were evaluated on basis of clinical assessments. Between-group differences were tested using ANOVA or ANCOVA, as appropriate. Statistical significance was assumed at a two-tailed p value of/=0.05.Two hundred and twelve gastric ulcer patients (median age 53.3 years) and 306 duodenal ulcer patients (median age 49.7 years) were recruited; 71.8 and 85% of gastric and duodenal ulcer patients, respectively, completed the study. Ulcers were successfully healed in 64.29, 67.14, and 63.89% of gastric ulcer patients and 78.85, 83.65, and 78.57% of duodenal ulcer patients after treatment with 20 mg omeprazole, 5 mg ilaprazole, and 10 mg ilaprazole, respectively. Most patients (90%) became asymptomatic after treatment. At the dosages administered, both drugs exhibited similar efficacy and a similar safety profile.Ilaprazole is as tolerable, safe, and efficacious as omeprazole in the treatment of gastroduodenal ulcers, at a much lower dose (5 vs. 20 mg omeprazole).

Objectives/Background The role of Helicobacter pylori infection in functional dyspepsia (FD) remains controversial. Several randomized controlled trials involving populations in the West, observed no statistically significant advantage over placebo. However, none of these studies involved Asian populations which have high infection rates. Methods A double blind, randomized, placebo-controlled trial of H. pylori eradication for FD was conducted in our Singapore-based Asian population. Forty-one patients received active treatment consisting of a 1-week course of omeprazole 20 mg once daily, clarithromycin 250 mg twice daily and tinidazole 500 mg twice daily whereas another 41 patients received matching placebo tablets. A dyspepsia score was derived by grading 5 dyspeptic symptoms on a Likert scale. Symptom assessment and urea breath test were repeated at 6 weeks, 6 and 12 months from the start of treatment. The primary end point was symptom resolution, defined as a dyspepsia score of 0 or 1 at the end of 12 months follow-up. Results On intention-to-treat analyses, symptom resolution was observed in 24% of patients on active treatment and 7% on placebo; the difference in proportion of patients with symptom resolution was statistically significant (P=0.02, 95% confidence interval: 1.1-17.7). H. pylori eradication rates perprotocol and intention-to-treat were 80.0 and 68.3%, on active treatment and 5.6 and 4.9% on placebo (both P values

Data on Asian patients who present to primary care physicians with dyspepsia are limited.To determine predictors of response to a trial of proton pump inhibitor therapy.One hundred ninety patients presenting to their general practitioners with dyspeptic symptoms but without alarm symptoms, underwent endoscopy and were subsequently treated with 20 mg of esomeprazole twice a day for 2 weeks. Possible predictors of response were assessed before treatment. Dyspeptic symptoms were scored at baseline and at the end of treatment. Excellent response and poor response were defined as end of treatment score ofor=1 and failure to achieveor=50% reduction in symptom scores.On bivariate analysis male sex and havingor=2 concurrent dyspeptic symptoms predicted excellent response, whereas bloating as most bothersome symptom,2 dyspeptic symptoms, anxiety, and irritable bowel syndrome predicted poor response. On multivariate analysis, male sex andor=2 dyspeptic symptoms, and bloating remained significant predictors of excellent and poor responses, respectively.Predictors of response to proton pump inhibitor trial that could be easily assessed in a primary care clinic were identified. In our population the response was not as favorable as suggested by clinical trials. Frequent overlap with irritable bowel syndrome seems to be an important factor.

SUMMARY Background: Alpha-interferon has been found to inhibit hepatitis B virus (HBV) replication in Chinese patients with chronic HBV infection although a sustained effect was rarely achieved in those with normal pre-treatment serum alanine amino transferase (ALT) levels. Prednisolone priming has been found to be beneficial over treatment with interferon alone in these subjects. We studied the effect of steroid pre-treatment followed by recombinant interferon alpha-2a in the treatment of asymptomatic HBV carriers with positive hepatitis Be antigen (HBeAg), hepatitis B viral DNA (HBV-DNA) and minimal changes in liver histology. Methods: The treatment regimen included a 6-week prednisolone priming, a 2 week rest followed by 14 weeks of three times weekly 9 mega units of interferon alpha-2a injection and 52 weeks of follow-up. There were seven patients in the treatment group and seven controls. Results: The mean age, pre-treatment ALT (normal in all except for one in each of the treatment and control groups), HBV-DNA levels and histological scores were similar in the two groups. Serum HBV-DNA levels fell in six patients during treatment and became undetectable in two of them by the end. During follow-up, serum HBV-DNA returned to pre-treatment levels in all patients. None of the treated patients had HBeAg sero-conversion and none of the controls had spontaneous clearance of HBV-DNA or sero-conversion of HBeAg. No improvement of liver histology was observed in any of the treated patients. There were only mild flu-like side-effects noted and interferon alpha-2a was well tolerated at the doses given among treated patients. Conclusion: Prednisolone priming followed by interferon alpha-2a treatment has no beneficial effect on HBV carriers in the early stages of chronic hepatitis B infection.

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.

Background/aims To study the practice of clinicians in the diagnosis and treatment of H. pylori for peptic ulcer bleeding, and the diagnostic yield of H. pylori tests in various situations. Materials and methods All consecutive patients aged ≥18 years who underwent esophagogastroduodenoscopy for the indications of coffee-grounds vomitus, hematemesis or melena with endoscopically diagnosed peptic ulcers were included. Results 374 patients were included. H. pylori testing was performed during acute bleeding for 296 patients. 80% of patients who tested negative for H. pylori during the acute episode were planned for repeat H. pylori testing. 11/88 patients who tested negative for H. pylori during the acute episode were positive for H. pylori during repeat testing (diagnostic yield 12.5%). Prior proton-pump inhibitor and antibiotic ingestion within 4 weeks of presentation was associated with lower diagnostic yield for H. pylori. On multivariate analysis, patient's age, systolic blood pressure, heart rate, activated partial thromboplastin time, and need for endoscopic treatment were associated with failure to take biopsies for H. pylori testing during acute episode. 100/106 patients tested positive for H. pylori during the acute episode of gastrointestinal bleeding had H. pylori treatment. Conclusion Repeat H. pylori testing after index negative H. pylori testing during acute episodes gave a diagnostic yield of 12.5%, reinforcing the importance of repeat testing.

Background Peptic ulcers due to nonsteroidal anti-inflammatory drug (NSAID) use may have contributed to the static prevalence of ulcer disease in Asia. Goal We aimed to determine the current etiology of peptic ulcer disease in Singapore. Study Consecutive patients undergoing esophagogastroduodenoscopy who had not been exposed to antibiotics, or antiulcer therapy within the past 6 months, and in whom peptic ulcers were found, were prospectively studied. Before endoscopy, patients were interviewed regarding the use of NSAID or aspirin. During endoscopy, antral biopsies were obtained for urease test and histology. Serum thromboxane B2 levels were compared with those of healthy volunteers. Results Peptic ulcers were detected in 600 patients during a 2-year period. The ulcers were negative for Helicobacter pylori in 212 patients (35.3%) and these H. pylori negative ulcers were related to NSAID use in 68.9% of cases. On the basis of serum thromboxane B2 levels, 30.8% of the patients with non-H. pylori non-NSAID were considered to have consumed NSAID. Conclusions H. pylori negative peptic ulcer makes up a significant proportion of peptic ulcer in Singapore. Most of these ulcers were related to NSAID use. Serum thromboxane profile suggested surreptitious NSAID use in many of the non-H. pylori and apparently non-NSAID patients.

Background: Little is known about the current status of endoscopic ultrasonography (EUS) training in the Asia–Pacific region. The aim of the present study was to assess EUS practice and training in the Asia–Pacific region and seek to identify areas where the development of EUS expertise could be further enhanced. Methods: A direct mail survey was sent out to 87 practising endosonographers in various parts of the Asia–Pacific region outside of Japan. They were asked to report on their prior training, utilization of EUS, and EUS training in their country. Results: The respondents (n = 71) were mostly young (median age 40 years), male (97%), practising in academia (36.6%) or public hospitals (50.7%) and fairly experienced (median 5 years) in EUS practices; they had performed a median of 500 procedures in their career. Among them, 49.3% were self-taught. Only 22.5% and 21.1% had undergone formal overseas fellowship lasting ≥6 months, and local gastrointestinal fellowships of various durations, respectively. Fifty-six percent were currently involved in EUS teaching. Most (90%) thought that a formal EUS training fellowship is necessary for acquiring acceptable competence and there should be a minimum number (median 100) of supervised procedures performed and minimum amount of time (median 6 months) spent on training. Conclusions: Although EUS practitioners in the Asia–Pacific region were not behind their European or US counterparts in hands-on experience, the lack of formal EUS training programs and opportunities remains an area of concern. For the region to increase EUS utilization, the current shortage of training opportunities needs to be addressed.

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.

This study aimed to determine time trends in the frequency of endoscopic esophagitis, and Helicobacter pylori (H. pylori) infection in a large Singaporean teaching hospital over a 10-yr period.We studied a consecutive series of 16,375 patients who had been newly referred for diagnostic esophagogastroduodenoscopy from 1992 to 2001. All endoscopic findings were prospectively recorded. From 1995, an antral biopsy was taken from 6,185 unselected patients for an in-house biopsy urease test. Endoscopic esophagitis was defined as the presence of erosions and/or ulceration. The relationship between erosive esophagitis and various relevant factors was analyzed.The overall prevalence of endoscopic esophagitis was 6.9% (95% CI, 6.5-7.3). It was 7.3% (95% CI, 6.2-8.4) in patients with a positive urease test, and 9.0% (95% CI, 8.1-9.9) in those in whom the urease test was negative (p0.001). From 1992 to 2001, the frequency of endoscopic esophagitis increased (p0.001 for trend) while that of positive urease test decreased from 1995 to 2001 (p0.001 for trend). The increase in the prevalence of endoscopic esophagitis (RR 1.99, 95% CI 1.18-3.36, p= 0.0098), and its inverse relationship with positive urease test results (RR 0.991, 95% CI 0.983-0.999, p= 0.049) remained significant even after adjusting for age, gender, ethnic distribution, and hiatal hernia.The frequency of endoscopic esophagitis increased in Singapore from 1992 to 2001. This increase within a short period of time suggests that environmental factors, of which the decreasing rate of H. pylori infection may be one, are important in the pathogenesis of gastroesophageal reflux disease.

Background Severe acute respiratory syndrome (SARS) is a newly recognized infectious disease that has recently emerged in East Asia and North America. Although the clinical features of acute infection have been well described, mildly symptomatic or asymptomatic infections have not been well characterized. Objective To assess the spectrum of illness in health-care workers (HCWs). Methods A prospective seroepidemiologic cohort study was conducted on 372 HCWs in a large teaching hospital in Singapore who were both exposed and not exposed to patients with SARS. Participating HCWs completed a questionnaire and provided paired serum samples, which were analyzed by 2 different laboratories blinded to clinical data, by use of an enzyme-linked immunosorbent assay based on a protocol developed by the Centers for Disease Control and Prevention and a dot-blot immunoassay, with confirmation by a viral neutralization assay. Results A total of 21 patients with SARS were treated at our hospital. They were associated with transmission to 14 staff members, patients, and visitors in our hospital. Of the 372 HCWs participating in the present study, 8 were found to have positive antibodies to the SARS coronavirus in both samples by use of both test methods, and 6 had pneumonia and had been hospitalized for either probable or suspected SARS infection, whereas 2 had fever but did not have changes on chest radiographs. All seropositive HCWs had been exposed either directly or indirectly to patients with SARS. No asymptomatic, nonexposed staff members were found to be seropositive. There was a trend towards protection for HCWs who, while fully protected, had had contact with patients with SARS. Conclusions Although the majority of cases of SARS are associated with pneumonia, a small number of mildly symptomatic individuals do seroconvert. HCWs who are exposed to patients with SARS can be infected with SARS, regardless of the intensity of exposure. This has implications for surveillance and infection control planning, in the event that SARS returns next winter.

Natural orifice transluminal endoscopic surgery (NOTES) is a novel surgical procedure during which abdominal operations can be performed with an endoscope passed through a natural orifice through an internal incision in the stomach, vagina, bladder or colon. NOTES is still evolving and many barriers stand on its way before it can gain acceptance in modern surgical practice. Effective access to the peritoneal cavity, closure techniques of the natural orifice access sites, development of a multitasking platform to accomplish procedures and support for special orientation are only a handful of its known limitations. Although the endoscope and conventional tools are useful for simple procedures, many important and complicated procedures are currently not possible due to limitation of degree of freedom (DOF) of the end effectors. We have developed a Master and Slave Transluminal Endoscopic Robot (MASTER) with nine degrees of freedom (DOF) in end effectors, which are long and flexible so as to enhance endoscopic procedures and NOTES. Using MASTER we have successfully performed endoscopic sub-mucosal dissections (ESD) to segmental hepatectomies in animal models. Thus, the MASTER robotic system shows great potential to perform new surgical procedures that are otherwise not possible with conventional endoscopic tools.

Colorectal cancer can be prevented if detected early (e.g., precancerous polyps-adenoma). Endoscopic differential diagnosis of hyperplastic polyps (that have little or no risk of malignant transformation) and adenomas (that have prominent malignant latency) remains an unambiguous clinical challenge. Raman spectroscopy is an optical vibrational technique capable of probing biomolecular changes of tissue associated with neoplastic transformation. This work aims to apply a fiber-optic simultaneous fingerprint (FP) and high wavenumber (HW) Raman spectroscopy technique for real-time in vivo assessment of adenomatous polyps during clinical colonoscopy. We have developed a fiber-optic Raman endoscopic technique capable of simultaneously acquiring both the FP (i.e., 800-1800 cm(-1)) and HW (i.e., 2800-3600 cm(-1)) Raman spectra from colorectal tissue subsurface (

In the development and progression of hepatocellular carcinoma, tumor hypoxia plays an important role, as does activation of the Wnt pathway. The aim of this study was to characterize the expression and interrelationship between hypoxia and Wnt-pathway-associated proteins as prognostic factors for hepatocellular carcinoma. Expression of HIF-1α, CA-IX, E-cadherin, β-catenin, and Ki-67 was assessed by immunohistochemistry in 179 primary hepatocellular carcinoma cases. Univariate and multivariate analyses were performed to assess the relationship between the clinicopathological factors, protein expression, overall survival (OS), and recurrence-free survival (RFS). By univariate analysis, tumor stage, size, satellitosis, and vascular invasion were confirmed as prognostic factors for worse OS and RFS. High expression of HIF-1α, CA-IX, β-catenin, Ki-67, and E-cadherin was observed in 60, 15, 64, 8, and 64 % of tumors, respectively, and this was significantly associated with poor OS. CA-IX, HIF-1α, and E-cadherin were independent predictors of poor prognosis. We stratified 169 patients into four groups according to the expression level of hypoxia and Wnt pathway markers. The group with high expression of both hypoxia and Wnt-pathway-associated proteins showed worst OS. The poor survival of this group was also significant in patients with early stage disease and tumor size of less than 5 cm (p

A major reason impeding the growth of endoscopic ultrasound (EUS) in Asia is the lack of training availability. We aimed to prospectively evaluate the effectiveness of a short-term structured EUS training program in improving the knowledge and skill of EUS among trainees.The study was conducted in six workshops in six countries including Sri Lanka, Pakistan, Thailand, Vietnam, Singapore and Philippines, within a year. Trainees were evaluated using written and skill tests before and after completion of the training.Pre- and post-workshop written tests from a total of 62 trainees were analyzed. Compared with pre-training, the trainees improved significantly in the overall mean (± SD) scores after the training (66.0 ± 0.3% to 77.5 ± 0.2%, P0.0001). Thirty-one trainees were randomly selected to undergo a skill test before and after the course. Compared with pre-training, the proportions of trainees who succeeded in locating each structure post-training were: celiac axis (36-80.5%), pancreatic body (51.5-80.5%), pancreatic body and tail (42-77.5%), splenic vein and artery (48.5-84%), left kidney (60-83%), and spleen (47-83%). Overall, there was a significant improvement in the proportion of trainees' successful localization of structures post-training compared to before training (P0.0001).Following a structured training program, trainees' knowledge and skills in EUS improved significantly. Structured training courses appear to be an effective way of imparting EUS knowledge and skills to aspiring endosonographers in the Asian region.

We aimed to determine whether healthy volunteers with normal pH monitoring study results experienced heartburn or discomfort during an esophageal acid perfusion test. We performed an esophageal acid perfusion test, followed by ambulatory esophageal pH monitoring, in 15 healthy and asymptomatic volunteers (aged 19 to 34 years). The results of the acid perfusion test were correlated with those of the pH monitoring. Three subjects (20%) reported chest discomfort during acid perfusion. The pH data in all subjects were within our laboratory reference ranges; the median (range) percent total time at pH < 4 being 1.7 (0.2–4.0)% [laboratory reference, median (range), 3.0 (0.2–4.0)%]. We concluded that direct infusion of acid onto the distal esophagus can produce discomfort akin to that of gastroesophageal reflux disease in asymptomatic adult volunteers, even in the absence of excessive esophageal acid exposure.

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.

Probiotics have treatment efficacy in irritable bowel syndrome (IBS), but the exact mechanism remains obscure. One hypothesis is the mediation of melatonin levels, leading to changes in IBS symptoms. The purpose of this study was to evaluate the effects of a probiotic, VSL#3, on symptoms, psychological and sleep parameters, and pain sensitivity in IBS, and relate these parameters to in vivo melatonin levels. Forty-two IBS patients were randomly assigned to receive VSL#3 or placebo for 6 weeks. Subjects completed bowel and psychological questionnaires, underwent rectal sensitivity testing and saliva melatonin assays. Abdominal pain duration and distension intensity decreased significantly in the probiotic group, along with an increase in rectal distension pain thresholds. A correlation between increase in pain tolerance and improvement in abdominal pain scores (r = 0.51, p = 0.02) was seen with probiotic. There was an increase in salivary morning melatonin levels in males treated with VSL#3, which correlated (r = 0.61) with improved satisfaction in bowel habits. When grouped based on baseline diurnal melatonin levels, patients with normal diurnal fluctuations showed an increase in morning melatonin levels with VSL#3 treatment, which significantly correlated with improved satisfaction in bowel habits (r = 0.68). They also had reduced symptom severity scores and abdominal pain duration when treated with VSL#3, as well as satisfaction with bowel movements and quality-of-life. VSL#3 improved symptoms and increased rectal pain thresholds. Symptom improvement correlated with a rise in morning melatonin, significant in males and subjects with normal circadian rhythm. This suggests that probiotics may act by influencing melatonin production, hence modulating IBS symptoms, in individuals with a normal circadian rhythm.

The purpose of this study was to determine (1) the diagnostic yield for endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in patients with pancreatic cystic lesions, (2) additional value of EUS-FNA over EUS alone in the diagnosis of pancreatic cysts, and (3) diagnostic sensitivity and specificity of EUS and EUS-FNA in the subset of patients where histopathology of surgical specimens were available.All patients who underwent EUS examination for the evaluation of pancreatic cystic lesions in six Asian centres were included in the study.Of 298 patients with pancreatic cysts who underwent EUS, 132 (44.3 %) underwent FNA. In the entire cohort, pseudocysts and intraductal papillary mucinous neoplasm (IPMN) were the predominant cystic lesions. The cytologic yield of EUS-FNA was 47 %. On univariate analysis, factors associated with higher cytologic yield included vascular involvement on EUS, presence of solid cystic component, and increased number of needle passes during EUS-FNA. On multivariate analysis, presence of solid cystic components and increased number of needle passes during EUS-FNA were associated with higher diagnostic yield of EUS-FNA. For pancreatic cysts with a solid component, the diagnostic yield of EUS-FNA increased significantly from 44 % with one pass to 78 % with more than one pass (p = 0.016). In the absence of a solid component, the diagnostic yield was 29 % with one pass and was not significantly different from the diagnostic yield of 50 % with more than one pass, p = 0.081.The cytologic yield of EUS-FNA was 47 %. When a solid component was present in the cyst, doing more than one pass during EUS-FNA increased its diagnostic yield.

Background and study aim: Treatment of ulcerative colitis should be tailored to the severity of colonic inflammation, which in the past has been gauged mainly by clinical features and biochemical parameters. Recently, mucosal healing has been proposed as a standard to guide therapy. The aim of this multicenter study was to test whether mucosal appearance, as reported by colon capsule endoscopy (CCE), can be used to differentiate active from inactive ulcerative colitis. Patients and methods: Adult patients from Hong Kong, Singapore, and Taiwan who were suspected or known to have ulcerative colitis were included in this prospective study. CCE and conventional optical colonoscopy were offered to these patients on the same day after receiving standard bowel preparation. The primary endpoint was the accuracy of CCE in assessing colonic inflammation (defined as the presence of ulcers, erythema, erosions, edema, exudates in mucosa), using optical colonoscopy as the gold standard. Results: At total of 100 patients (42 females; median age 50 years; range 22 - 68 years) were enrolled. Four cases were excluded from the analysis due to technical failure or slow transit of the capsule. In nine patients, the capsule was not excreted within 8.5 hours and required retrieval during colonoscopy. The sensitivity of CCE to detect active colonic inflammation was 89 % (95 % confidence interval [CI] 80 - 95) and specificity was 75 % (95 %CI 51 - 90). The positive and negative predictive values of CCE for colonic inflammation were 93 % (95 %CI 84 - 97) and 65 % (95 %CI 43 - 83), respectively. No serious adverse event related to the CCE procedure or preparation was reported. Conclusion: CCE is a safe procedure to monitor mucosal healing in ulcerative colitis. However, at this stage, CCE cannot be recommended to replace conventional colonoscopy in the management of this condition. © Georg Thieme Verlag KG Stuttgart · New York.

Background & Aims Endoscopic submucosal dissection (ESD) is a new technique for endoscopic resection of early-stage gastrointestinal cancers. Though ESD achieves high rate of en bloc resection, it is technically difficult to master. The development of a novel robotic endoscopic system that has 2 arms attached to an ordinary endoscope—Master and Slave Transluminal Endoscopic Robot (MASTER)—has improved the performance of complex endoluminal procedures. We evaluated the efficacy of MASTER-assisted ESD in treatment of patients with early-stage gastric neoplasia. Methods We performed a multicenter prospective study of 5 patients with early-stage gastric neoplasia, limited to the mucosa. After markings and circumferential mucosal incision, all submucosal dissections were performed using the MASTER system. We measured baseline demographics, tumor characteristics, and perioperative and clinical outcomes. Results All patients underwent successful MASTER-assisted ESD. The mean submucosal dissection time was 18.6 minutes (median, 16 minutes; range, 3–50 minutes). No perioperative complications were encountered. Three patients were discharged from the hospital within 12 hours and 2 on the third day after the procedures. Two patients were found to have intramucosal adenocarcinoma, 1 had high-grade dysplasia, 1 had low-grade dysplasia, and 1 had a hyperplastic polyp. The resection margins were clear of tumors in all 5 patients. No complications were observed at the 30-day follow-up examination. Follow-up endoscopic examinations revealed that none of the patients had residual or recurrent tumors. Conclusions A flexible endoscopy robotic system can be used to perform ESD and effectively treat patients with early gastric neoplasia.

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.