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.
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.
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.
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.
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.
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.
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.
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.
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.
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).
Endoscopy within 13 h of presentation was associated with lower mortality in high-risk but not low-risk NVUGIB.
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.
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.
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.
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.
CD44 and Musashi-1 are frequently expressed in both premalignant gastric lesions and invasive GC, whereas CD133 expression is restricted mainly to neoplastic tissues.
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.
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.
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.
Summary
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.
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