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.

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.

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.

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.

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.

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.

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.

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.

Subcutaneously administered recombinant human beta-interferon in the treatment of chronic hepatitis B virus infection.

BACKGROUND: Treatment of chronic replicative hepatitis B virus (HBV) infection is aimed at stopping viral replication and preventing the development of chronic liver disease. beta-Interferon treatment has been less well studied than alpha-interferon. METHODS: The efficacy and tolerability of a 6-month course of subcutaneously administered human recombinant beta-interferon (rINF-beta ser) was studied and the results of a low-dose regime compared with a high-dose regime. Twenty patients (17 men and three women), aged 24-54 years, with chronic hepatitis B virus infection (all hepatitis B surface antigen-positive with detectable HBV-DNA in their sera for at least 3 months prior to therapy) were randomized into two treatment groups of 10 patients each. The low-dose group received 6 x 10(6) U/dose and the high-dose group received 30 x 10(6) U/dose, both groups receiving their respective doses three times a week initially for 1 month and continuing for a total of 6 months. RESULTS: The treatment was well tolerated in both groups. None of the patients required dosage reduction or cessation of treatment because of side-effects. HBV-DNA decreased in all patients during treatment, demonstrating the anti-viral efficacy of rINF-beta ser, and was undetectable in 20 and 40% of patients receiving low-dose and high-dose regimes, respectively, at the end of 6 months treatment (P = N.S.). One year after completion of treatment, HBV-DNA was undetectable in 50 and 30% of patients in the low-dose and high-dose groups, respectively (P = N.S.). However, only one patient achieved seroconversion with loss of the hepatitis B surface antigen and appearance of an antihepatitis B 'e' antigen at the end of 18 months. CONCLUSION: This study shows that subcutaneously administered rINF-beta ser is well tolerated, but the optimal dose and duration of treatment still needs to be defined by further studies.

Outcome of lateral pancreaticojejunostomy in the management of chronic pancreatitis with nondilated pancreatic ducts.

Lateral pancreaticojejunostomy has demonstrated variable success in the management of chronic pancreatitis associated with ductal dilation, but its role in patients with nondilated ducts is poorly defined. The aim of this study was to assess the outcome of lateral pancreaticojejunostomy in chronic pancreatitis with nondilated pancreatic ducts. The records of all patients who underwent lateral pancreaticojejunostomy with a pancreatic duct measuring less than 7 mm in diameter were reviewed. Seventeen patients underwent lateral pancreaticojejunostomy for chronic pancreatitis and intractable pain between 1995 and 1996. Endoscopic retrograde cholangiopancreatography demonstrated features of chronic pancreatitis that were mild in seven patients, moderate in five, and severe in four. Postoperative complications occurred in two patients (11.7%). There were no deaths. Mean length of follow-up was 10.3 months (range 3 to 16 months). Rehospitalization for recurrent pancreatitis or pain was necessary in 59% of patients. Emergency room visits were reported by 76%. Narcotic use continued in 88%, with 76% of the patients reporting their pain as the same or worse than before the operation, and 65% continuing to view their health status as poor. In chronic pancreatitis patients with a nondilated pancreatic duct, lateral pancreaticojejunostomy appears to be of little benefit with respect to pain relief, subsequent hospitalization, continued narcotic use, or overall health status.

Validation of [13C]urea breath test for Helicobacter pylori using a simple gas chromatograph-mass selective detector.

OBJECTIVE: Isotope ratio mass spectrometry (IRMS) is the accepted method for accurately measuring the 13CO2:12CO2 ratio in the non-invasive and non-radioactive [13C]urea breath test (13C-UBT) for Helicobactor pylori. The IRMS instrument, an expensive and highly specialized analyser, is rarely available. The objective of this project was to modify and validate the use of a simple bench-top gas chromatograph-mass selective detector (GC-MSD) for 13C-UBT. METHODS: Breath samples from 71 patients were taken at baseline and 30 min after ingestion of 100 mg [13C]urea. The breath samples were analysed using GC-MSD in the selected ion monitoring mode. The reference 13CO2:12CO2 ratio was from NBS19 obtained from the US National Institute of Standards and Technology. 13CO2:12CO2 ratios of the breath samples were determined. Excess delta per thousand (per mil, delta/thousand) of the 30 min sample over the baseline (deltadelta/thousand) of > or = 6deltadelta/thousand was considered H. pylori positive. Results from 13C-UBT and histology determined blind to each other were compared. RESULTS: The coefficient of variation of the reference 13CO2:12CO2 ratio was 0.06%. Using histology as the 'gold standard', the sensitivity (97.9%) and specificity (95.8%) of the GC-MSD 13C-UBT were comparable to those of other methods of H. pylori diagnosis. CONCLUSION: A gas chromatograph coupled to a mass selective detector that is available in many analytical and biomedical laboratories can be used for the 13C-UBT. This method will increase the availability and reduce the cost of this non-invasive, non-radioactive diagnostic test.

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.

Fatal lactic acidosis from imported phenformin--report of two cases.

This report describes two diabetic patients who presented with severe lactic acidosis. Both patients had been taking a medicine (phenformin) which they had obtained from China, and which has been withdrawn from Singapore since 1977. Both cases were admitted with severe metabolic acidosis and were treated with intravenous sodium bicarbonate and intensive care support with unsuccessful outcomes.

Standard oesophageal manometry in healthy adults in Singapore.

Data on oesophageal manometry in normal subjects in the East are limited. The aim of this study was to define standard oesophageal pressure values in a group of healthy adults in Singapore. Standard oesophageal manometry was performed on 26 asymptomatic volunteers (12 males and 14 females, aged 19 to 34 years) using the water-perfused capillary system and stationary pull-through technique. Median (range) lower oesophageal sphincter pressure, distal oesophageal contractile amplitude, distal oesophageal contractile duration and distal oesophageal contractile velocity were 13.6 (8.0 to 32.0) mmHg, 93.0 (41.0 to 143.0) mmHg, 3.8 (3.2 to 5.3) s and 3.6 (2.2 to 4.6) cm/s respectively. They were similar in males and females except for distal oesophageal contractile velocity which was higher in males than females [4.0 (3.1 to 4.6) cm/s versus 3.2 (2.2 to 4.4) cm/s, P < 0.01]. They were also generally in line with published normal values from Western countries. The present study helps to establish standards for normal manometric findings, at least among the young adults, in this part of the world.

Peliosis hepatis: a case report.

A 54-year-old man who presented with marked hepatomegaly and a liver scan suggestive of an infiltrative malignancy was found to have peliosis hepatis caused by androgenic steroids. A detailed and repeated drug history is necessary for making the correct diagnosis. Withdrawal of the offending drug is indicated and may result in reversal of this serious form of hepatic toxicity.

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.

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.