Artificial intelligence for gastroenterology: Singapore artificial intelligence for Gastroenterology Working Group Position Statement.

BACKGROUND: Successful implementation of artificial intelligence in gastroenterology and hepatology practice requires more than technology. There are ethical, legal, and social issues that need to be settled. AIM: A group consisting of AI developers (engineer), AI users (gastroenterologist, hepatologist, and surgeon) and AI regulators (ethicist and administrator) formed a Working Group to draft these Positions Statements with the objective of arousing public and professional interest and dialogue, to promote ethical considerations when implementing AI technology, to suggest to policy makers and health authorities relevant factors to take into account when approving and regulating the use of AI tools, and to engage the profession in preparing for change in clinical practice. STATEMENTS: These series of Position Statements point out the salient issues to maintain the trust between care provider and care receivers, and to legitimize the use of a non-human tool in healthcare delivery. It is based on fundamental principles such as respect, autonomy, privacy, responsibility, and justice. Enforcing the use of AI without considering these factor risk damaging the doctor-patient relationship.

CEACAM 6, a novel marker for the diagnosis of Barrett's esophagus.

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 <0.05 was considered significant. CEACAM6 expression increased from columnar lined epithelium (CLE) to BE with a subsequent decrease to dysplasia and adenocarcinoma. The expression of CEACAM6 was significant from CLE to BE at p 0.001, CLE to dysplasia at p 0.001, BE to dysplasia at p 0.006, CLE to adenocarcinoma at p 0.001 and BE to adenocarcinoma at p 0.001. There was no significant difference in expression between dysplasia and adenocarcinoma (P = 0.15). Our findings highlight the increasing expression of CEACAM6 from CLE to BE with a subsequent decrease to dysplasia and adenocarcinoma. In view of this, we advocate the utilization of this marker for the enhanced diagnosis of BE and for the distinction of BE and dysplasia.

RUNX3 is a novel negative regulator of oncogenic TEAD-YAP complex in gastric cancer.

Runt-related transcription factor 3 (RUNX3) is a well-documented tumour suppressor that is frequently inactivated in gastric cancer. Here, we define a novel mechanism by which RUNX3 exerts its tumour suppressor activity involving the TEAD-YAP complex, a potent positive regulator of proliferative genes. We report that the TEAD-YAP complex is not only frequently hyperactivated in liver and breast cancer, but also confers a strong oncogenic activity in gastric epithelial cells. The increased expression of TEAD-YAP in tumour tissues significantly correlates with poorer overall survival of gastric cancer patients. Strikingly, RUNX3 physically interacts with the N-terminal region of TEAD through its Runt domain. This interaction markedly reduces the DNA-binding ability of TEAD that attenuates the downstream signalling of TEAD-YAP complex. Mutation of RUNX3 at Arginine 122 to Cysteine, which was previously identified in gastric cancer, impairs the interaction between RUNX3 and TEAD. Our data reveal that RUNX3 acts as a tumour suppressor by negatively regulating the TEAD-YAP oncogenic complex in gastric carcinogenesis.

An updated Asia Pacific Consensus Recommendations on colorectal cancer screening.

OBJECTIVE: Since the publication of the first Asia Pacific Consensus on Colorectal Cancer (CRC) in 2008, there are substantial advancements in the science and experience of implementing CRC screening. The Asia Pacific Working Group aimed to provide an updated set of consensus recommendations. DESIGN: Members from 14 Asian regions gathered to seek consensus using other national and international guidelines, and recent relevant literature published from 2008 to 2013. A modified Delphi process was adopted to develop the statements. RESULTS: Age range for CRC screening is defined as 50-75 years. Advancing age, male, family history of CRC, smoking and obesity are confirmed risk factors for CRC and advanced neoplasia. A risk-stratified scoring system is recommended for selecting high-risk patients for colonoscopy. Quantitative faecal immunochemical test (FIT) instead of guaiac-based faecal occult blood test (gFOBT) is preferred for average-risk subjects. Ancillary methods in colonoscopy, with the exception of chromoendoscopy, have not proven to be superior to high-definition white light endoscopy in identifying adenoma. Quality of colonoscopy should be upheld and quality assurance programme should be in place to audit every aspects of CRC screening. Serrated adenoma is recognised as a risk for interval cancer. There is no consensus on the recruitment of trained endoscopy nurses for CRC screening. CONCLUSIONS: Based on recent data on CRC screening, an updated list of recommendations on CRC screening is prepared. These consensus statements will further enhance the implementation of CRC screening in the Asia Pacific region.

A morpho-molecular prognostic model for hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the third common cause of cancer-related deaths and its prognostication is still suboptimal. The aim of this study was to establish a new prognostication algorithm for HCC. METHODS: In all, 13 biomarkers related to the etiopathogenesis of HCC were evaluated by immunohistochemistry using tissue microarrays containing 121 primary HCC resection cases, and validated in subsequent cohort of 85 HCC cases. The results were compared with Affymetrix Gene Chip Human Genome U133Plus microarray data in a separate cohort of 228 HCC patients. RESULTS: On immunohistochemical evaluation and multivariate Cox regression analysis p53, alpha fetaprotein (AFP), CD44 and CD31, tumour size and vascular invasion, were significant predictors for worse survival in HCC patients. A morpho-molecular prognostic model (MMPM) was constructed and it was a significant independent predictor for overall survival (OS) and relapse-free survival (RFS) (P<0.000). The OS and RFS of HCC(low) was higher (104 and 78 months) as compared with HCC(high) (73 and 43 months) (P<0.000 for OS and RFS). Hepatocellular carcinoma patients with higher stage (III+IV), >5 cm tumour size, positive vascular invasion and satellitosis belonged to HCC(high) group. The validation group reproduced the same findings. Gene expression analysis confirmed that 7 of the 12 biomarkers were overexpressed in >50% of tumour samples and significant overexpression in tumour samples was observed in AFP, CD31, CD117 and Ki-67 genes. CONCLUSION: The MMPM, based on the expression of selected proteins and clinicopathological parameters, can be used to classify HCC patients between good vs poor prognosis and high vs low risk of recurrence following hepatic resection.

Sequential expression of putative stem cell markers in gastric carcinogenesis.

BACKGROUND: Gastric carcinogenesis has been well documented in the step-wise histopathological model, known as Correa pathway. Several biomarkers including CD44, Musashi-1 and CD133 have been reported as putative stem cell (PSC) markers. METHODS: We investigated expression of PSC markers CD44, Musashi-1 and CD133 in relation to gastric carcinogenesis and prognosis and chemoresponse. Immunohistochemistry staining was performed in gastric cancer (GC) clinical specimens representing different steps of the Correa pathway. Gastric cancer samples taken before and after neoadjuvant chemotherapy with docetaxel, cisplatin and capecitabine (DCX) were also evaluated for PSC marker expression. RESULTS: We showed that the expression of three PSC markers was significantly elevated in GC relative to normal gastric mucosa (P<0.001 for each marker). Precancerous lesions, including intestinal metaplasia and dysplasia, demonstrated increased expression of CD44 and Musashi-1. CD133 was predominantly expressed along the border between intramucosal carcinoma and connective tissue at later stages. High CD44 and CD133 expression showed prognostic value for worse patient survival (P=0.014 and P=0.019, respectively). A small number of tumours with high expression of CD44 and CD133 showed pathological response to DCX-based neoadjuvant chemotherapy. CONCLUSION: CD44 and Musashi-1 are frequently expressed in both premalignant gastric lesions and invasive GC, whereas CD133 expression is restricted mainly to neoplastic tissues.

In vivo diagnosis of esophageal cancer using image-guided Raman endoscopy and biomolecular modeling.

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.

Urgent endoscopy is associated with lower mortality in high-risk but not low-risk nonvariceal upper gastrointestinal bleeding.

BACKGROUND AND STUDY AIMS: The role of urgent endoscopy in high-risk nonvariceal upper gastrointestinal bleeding (NVUGIB) is unclear. The aim of this study was to determine whether esophagogastroduodenoscopy (EGD) performed sooner than the currently recommended 24 h in high-risk patients presenting with NVUGIB is associated with lower all-cause in-hospital mortality. METHODS: All adult patients undergoing EGD for the indications of coffee-grounds vomitus, hematemesis or melena at a university hospital over an 18-month period were enrolled. Patients with variceal and lower gastrointestinal bleeding were excluded. Data were prospectively collected. RESULTS: A total of 934 patients were included. The area under the receiver operating characteristic curve (AUROC) for the Glasgow-Blatchford score (GBS) was 0.813 for predicting all-cause in-hospital mortality, with a cut-off score of ≥ 12 resulting in 90 % specificity. In low-risk patients with GBS < 12, presentation-to-endoscopy time in those who died and in those who survived was similar. In high-risk patients with GBS of ≥ 12, presentation-to-endoscopy time was significantly longer in those who died than in those who survived. Multivariate analysis of the high-risk cohort showed presentation-to-endoscopy time to be the only factor associated with all-cause in-hospital mortality. For high-risk patients, the AUROC for presentation-to-endoscopy time in predicting all-cause in-hospital mortality was 0.803, with a sensitivity of 100 % at the cut-off time of 13 h. All-cause in-hospital mortality in high-risk patients was significantly higher in those with presentation-to-endoscopy time of > 13 h compared with those undergoing endoscopy in < 13 h from presentation (44 % vs. 0 %; P < 0.001). CONCLUSIONS: Endoscopy within 13 h of presentation was associated with lower mortality in high-risk but not low-risk NVUGIB.

Ministry of health clinical practice guidelines: cancer screening.

The Ministry of Health publishes national clinical practice guidelines to provide doctors and patients in Singapore with evidence-based guidance on managing important medical conditions. This article reproduces the introduction and executive summary (with key recommendations from the guidelines) from the Ministry of Health clinical practice guidelines on cancer screening, for the information of readers of the Singapore Medical Journal. Chapters and page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Ministry of Health website (http://www.moh.gov. sg/mohcorp/publications.aspx?id=24018). The recommendations should be used with reference to the full text of the guidelines. Following this article are multiple choice questions based on the full text of the guidelines.

Near-infrared Raman spectroscopy for early diagnosis and typing of adenocarcinoma in the stomach.

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.

Readiness exercise to combat avian influenza.

AIM: To examine the readiness of our hospital for the potential pandemic threat of avian influenza, we developed and implemented simulation case scenarios in our hospital. METHODS: Two volunteers, who assumed the identity of 'actual' patients, were trained to simulate acute respiratory symptoms following a visit to an avian influenza-affected area, and their identities and locations were kept confidential prior to the readiness exercise. A team of auditors was stationed at high-risk areas to assess adherence to the use of personal protective equipment (PPE) and infection control procedures. RESULTS: A total of 324 healthcare workers and 84 administrators participated in this hospital-wide exercise. Following disclosure of their symptoms, the 'patients' were masked and isolated in negative-pressure rooms. A quarantine order was enforced on 38 inpatients and 45 healthcare workers who were present in the affected wards at the time of the exercise, which mandated the use of PPE. Although all affected healthcare workers were competent in the use of PPE, we observed breaches in PPE and isolation procedures in eight medical and nursing students, and 10 healthcare attendants. The exercise concluded after H5N1 tests returned negative. CONCLUSION: We recommend the use of case simulation as an effective means of assessing potential breaches in infection control procedures.

Asia Pacific consensus recommendations for colorectal cancer screening.

Colorectal cancer (CRC) is rapidly increasing in Asia, but screening guidelines are lacking. Through reviewing the literature and regional data, and using the modified Delphi process, the Asia Pacific Working Group on Colorectal Cancer and international experts launch consensus recommendations aiming to improve the awareness of healthcare providers of the changing epidemiology and screening tests available. The incidence, anatomical distribution and mortality of CRC among Asian populations are not different compared with Western countries. There is a trend of proximal migration of colonic polyps. Flat or depressed lesions are not uncommon. Screening for CRC should be started at the age of 50 years. Male gender, smoking, obesity and family history are risk factors for colorectal neoplasia. Faecal occult blood test (FOBT, guaiac-based and immunochemical tests), flexible sigmoidoscopy and colonoscopy are recommended for CRC screening. Double-contrast barium enema and CT colonography are not preferred. In resource-limited countries, FOBT is the first choice for CRC screening. Polyps 5-9 mm in diameter should be removed endoscopically and, following a negative colonoscopy, a repeat examination should be performed in 10 years. Screening for CRC should be a national health priority in most Asian countries. Studies on barriers to CRC screening, education for the public and engagement of primary care physicians should be undertaken. There is no consensus on whether nurses should be trained to perform endoscopic procedures for screening of colorectal neoplasia.

Diagnostic potential of near-infrared Raman spectroscopy in the stomach: differentiating dysplasia from normal tissue.

Raman spectroscopy is a molecular vibrational spectroscopic technique that is capable of optically probing the biomolecular changes associated with diseased transformation. The purpose of this study was to explore near-infrared (NIR) Raman spectroscopy for identifying dysplasia from normal gastric mucosa tissue. A rapid-acquisition dispersive-type NIR Raman system was utilised for tissue Raman spectroscopic measurements at 785 nm laser excitation. A total of 76 gastric tissue samples obtained from 44 patients who underwent endoscopy investigation or gastrectomy operation were used in this study. The histopathological examinations showed that 55 tissue specimens were normal and 21 were dysplasia. Both the empirical approach and multivariate statistical techniques, including principal components analysis (PCA), and linear discriminant analysis (LDA), together with the leave-one-sample-out cross-validation method, were employed to develop effective diagnostic algorithms for classification of Raman spectra between normal and dysplastic gastric tissues. High-quality Raman spectra in the range of 800-1800 cm(-1) can be acquired from gastric tissue within 5 s. There are specific spectral differences in Raman spectra between normal and dysplasia tissue, particularly in the spectral ranges of 1200-1500 cm(-1) and 1600-1800 cm(-1), which contained signals related to amide III and amide I of proteins, CH(3)CH(2) twisting of proteins/nucleic acids, and the C=C stretching mode of phospholipids, respectively. The empirical diagnostic algorithm based on the ratio of the Raman peak intensity at 875 cm(-1) to the peak intensity at 1450 cm(-1) gave the diagnostic sensitivity of 85.7% and specificity of 80.0%, whereas the diagnostic algorithms based on PCA-LDA yielded the diagnostic sensitivity of 95.2% and specificity 90.9% for separating dysplasia from normal gastric tissue. Receiver operating characteristic (ROC) curves further confirmed that the most effective diagnostic algorithm can be derived from the PCA-LDA technique. Therefore, NIR Raman spectroscopy in conjunction with multivariate statistical technique has potential for rapid diagnosis of dysplasia in the stomach based on the optical evaluation of spectral features of biomolecules.

Cancer screening in Singapore, with particular reference to breast, cervical and colorectal cancer screening.

Cancer is the leading cause of mortality in Singapore, accounting for 27.1% of deaths in 2004. The most common cancers are those of the lung, colon and rectum, liver, stomach, and prostate in men; and breast, colon and rectum, lung, ovary and cervix in women. Singapore has the highest age-adjusted breast cancer incidence in Asia. National population screening programmes have been implemented for breast and cervical cancer. BreastScreen Singapore (BSS), the first population-based nationwide mammographic breast-screening programme in Asia, was launched in 2002, incorporating international standards and practice guidelines. For improved quality assurance, two-view screening mammography is carried out. From January 2002 until March 2004, BSS conducted over 84,000 screens, with an overall recall rate of 9.5%, and an overall invasive cancer detection rate of 4.48 per 1000 screened. Close to 30% of the cancers diagnosed was ductal carcinoma in situ. Papanicolaou (Pap) smear screening for cervical cancer has been available opportunistically since 1964. The national CervicalScreen Singapore programme was launched in 2004, aiming to achieve coverage of 80% of targeted women by 2010. Colorectal cancer currently has the highest incidence of all cancers in Singapore. The health authorities advocate colorectal cancer screening for the average risk population, starting from age 50 years, but in the absence of a national screening programme, the reliance is on opportunistic screening.

Empirical treatment for the management of patients presenting with uninvestigated reflux symptoms: a prospective study in an Asian primary care population.

BACKGROUND: Data on Asian patients who present with reflux symptoms to their primary care physicians are limited. AIM: To determine whether empirical therapy without endoscopy is appropriate for patients who present to their primary care physicians with uninvestigated reflux symptoms without alarm symptoms. METHOD: Forty-seven patients presenting with uninvestigated, dominant reflux symptoms but without alarm features to their primary care physicians underwent endoscopy within 2 weeks of referral. Their endoscopic findings were compared with those of 162 primary care patients presenting with uninvestigated dominant dyspepsia. All patients, except those with ulcers, were treated with esomeprazole 20 mg b.d. for 2 weeks. Their treatment response was assessed at 2 weeks using a symptom score. RESULTS: Among patients with dominant reflux symptoms, 14 (30%) had erosive oesophagitis. No other clinically significant endoscopic findings were detected among them. In contrast, erosive oesophagitis and peptic ulcer were found in 13 (8%, P < 0.001 vs. reflux group), and 12 (7%, P = 0.06 vs. reflux group), respectively, of patients with dominant dyspepsia. Thirty-seven of forty-five (82%) of those with dominant reflux symptoms and 109 of 139 (78%; P = N.S. vs. reflux group) of those with dominant dyspepsia reported > or = 50% resolution of symptoms after esomeprazole treatment. CONCLUSIONS: Empirical proton pump inhibitor without endoscopy is reasonable for uninvestigated patients who present to primary care physicians with dominant reflux symptoms.

High-sensitivity C-reactive protein is predictive of medium-term cardiac outcome in high-risk Asian patients presenting with chest pain syndrome without myocardial infarction.

INTRODUCTION: High-sensitivity C-reactive protein (hs-CRP) has been shown to be predictive of cardiac events but data among Asians is comparatively few. We evaluated the role of hs-CRP in the prediction of adverse cardiac outcome in a cohort of high-risk patients presenting with chest pain syndrome without myocardial infarction (MI). MATERIALS AND METHODS: Three hundred and forty-seven patients were prospectively recruited over an 18-month period and patients with MI as documented by serial electrocardiogram abnormalities, and creatinine kinase or troponin elevation were excluded. Mean follow-up duration was 901 +/- 306 days. Kaplan-Meier and Cox proportional hazards modelling were used to evaluate outcome and determine association with predictor variables. RESULTS: The composite primary endpoint of cardiac mortality, non-fatal MI, cardiac failure or coronary revascularisation procedure (coronary artery bypass grafting or angioplasty) unrelated to the index admission was reached in 37 patients. History of previous MI (P = 0.002), presence of at least 1 coronary artery with > or =50% stenosis (P = 0.028) and elevated hs-CRP levels were associated with an adverse cardiac outcome (P = 0.001 for CRP in the upper quartile, and 0.002 for CRP > or = 1mg/L, respectively). None of the traditional cardiovascular risk factors (hypertension, diabetes mellitus, dyslipidaemia, significant family history, smoking, male gender and increased age) was predictive. Multivariate modelling showed elevated hs-CRP to confer the highest risk for an adverse cardiac outcome (P <0.001). CONCLUSION: Hs-CRP is useful in further stratifying high-risk multi-ethnic patients presenting with chest pain despite no evidence of MI. Close follow-up and aggressive management of these patients may be warranted.

Palliation of malignant gastric outlet obstruction caused by gastric cancer with self-expandable metal stents.

Gastric carcinoma is among the most common cancers worldwide. Surgery remains the mainstay of potentially curative treatments. Unfortunately, most patients have an advanced form of the disease. We evaluated our experience in palliating malignant gastric outlet obstruction caused by gastric cancer with expandable metal stents (Wallstent Enteral; Boston Scientific, Singapore). Six patients with a median age of 68 years (range, 45-88) underwent the procedure. Three had metastatic gastric cancer; two recurrent gastric cancer; and one locally advanced gastric cancer with poor comorbid status. After the procedure, five of the six patients were able to resume an oral feeding within 24 hours. One patient with gastric dysmotility caused by linitus plastica required nasogastric tube feeding. Three patients died during a median follow-up period of 4 weeks (range, 2-8). The other three patients were still well at a median follow-up period of 10 weeks (range, 5-12). There was no procedure-related mortality or morbidity, nor was there any stent migration or blockage in any of these patients. In conclusion, palliation of malignant gastric outlet strictures caused by gastric cancer with expandable metal stents is an effective and safe alternative to surgery, particularly in patients with postgastrectomy anastomotic recurrence and in those who are poor candidates for surgery. Patients who are not expected to survive beyond 1 month and those with linitus plastica and associated gastric dysmotility may not be appropriate candidates for such a procedure.

The decision-making value of magnetic resonance cholangiopancreatography in patients seen in a referral center for suspected biliary and pancreatic disease.

OBJECTIVE: To assess the ability of MRCP to alter the differential diagnosis and to prevent diagnostic and/or therapeutic ERCP. The diagnostic accuracy of magnetic resonance cholangiopancreatography (MRCP) for biliary and pancreatic disease is well documented. Some believe MRCP may prevent diagnostic ERCP or add useful information, however there are no reports of its impact on clinical management. METHODS: Consecutive patients referred for ERCP underwent clinic evaluation, then MRCP, and then ERCP. In Phase 1, the number of differential diagnoses and the perceived need for diagnostic ERCP were evaluated after each step by the endoscopist who performed the ERCP. In Phase 2, the process was repeated after presenting clinical information and MRCP results to different individual physicians: another endoscopist, a hepatologist, a radiologist, and a surgeon (all were blinded to ERCP results). RESULTS: Forty patients were enrolled. Clinical contexts were jaundice (19.7%), abnormal liver enzymes (42.6%), abdominal pain (11.5%), recurrent acute pancreatitis (11.5%), and suspected complications of chronic pancreatitis (14.7%). In Phase 1, adding MRCP information to diagnostic ERCP information did not change the mean number of differential diagnoses significantly and prevented no therapeutic ERCP. In Phase 2, adding MRCP to clinical information only (without ERCP) reduced the differential diagnosis significantly for the radiologist and the surgeon only and would have prevented < or =3% of diagnostic and therapeutic ERCP for all physicians. CONCLUSION: The value of MRCP information may be limited if patient selection is inappropriate and may differ in physicians depending on their speciality.

The status of the cagA gene does not predict Helicobacter pylori-associated peptic ulcer disease in Singapore.

Discrepancies among reports from different geographical regions worldwide on the association between the presence of cagA and peptic ulcer disease prompted this study on the predictive value of the cagA gene in Helicobacter pylori-associated gastroduodenal diseases in the Singapore population. H. pylori strains were obtained from 169 patients with a peptic ulcer, 83 with non-ulcer dyspepsia, and nine with gastric cancer. The presence of the cagA gene was evaluated by polymerase chain reaction (PCR). The expected 400 bp PCR product coding for the cagA gene was present in 232/261 (89%) H. pylori isolates. Of these, 151/169 (89%) strains from patients with peptic ulcer, 73/83 (88%) strains from patients with non-ulcer dyspepsia and 8/9 (89%) strains from cancer patients were positive for the cagA gene. There was no statistically significant difference between the prevalence of cagA-positive strains from patients with distinct clinical outcomes (p > 0.05). The prevalence of cagA-positive strains in the Singapore population is high regardless of clinical disease status. The results suggest that the cagA gene is not a universal virulence marker of H. pylori.

Association of peptic ulcer with increased expression of Lewis antigens but not cagA, iceA, and vacA in Helicobacter pylori isolates in an Asian population.

BACKGROUND: Studies in Western populations suggest that cagA, iceA, and vacA gene status in Helicobacter pylori isolates is associated with increased virulence and peptic ulcer disease. AIM: To investigate the relationship between peptic ulcer and expression of Lewis (Le) antigens as well as cagA, iceA, and vacA in H pylori isolates in Singapore. METHODS: Expression of Le antigens in H pylori isolates obtained from patients with dyspepsia was measured by enzyme linked immunosorbent assay. The cagA, iceA, and vacA status was determined by polymerase chain reaction. RESULTS: Of 108 H pylori isolates, 103 (95.4%) expressed Le(x) and/or Le(y), while Le(a) and Le(b) were expressed in 23 (21.3%) and 47 (43.5%) isolates, respectively. Expression of two or more Le antigens (Le(x), Le(y), Le(a), or Le(b)) was significantly higher in H pylori isolated from ulcer patients than in non-ulcer patients (89.6% v 73.2%, p=0.035). There were no significant differences in the prevalence of cagA or iceA1 in H pylori isolates from peptic ulcer and non-ulcer patients (86.6% v 90.2% for cagA; 70.1% v 68.3% for iceA1), and no association of peptic ulcer with any specific vacA genotype. CONCLUSIONS: The present study indicates that peptic ulcer disease is associated with increased expression of Lewis antigens but not cagA, iceA, or vacA genotype in H pylori isolates in our population. This suggests that cagA, iceA, and vacA are not universal virulence markers, and that host-pathogen interactions are important in determining clinical outcome.