Bcy Wong

Differential Helicobacter pylori infection rates in two contrasting gastric cancer risk regions of South China

Background: Carriers of Helicobacter pylori are believed to have a three‐ to six‐fold increased risk of developing gastric cancer. We have recently conducted a simultaneous cross‐sectional population study on the prevalence of H. pylori infection in a cohort of asymptomatic adult volunteers in two contrasting gastric cancer risk regions of South China, Hong Kong and Changle of Fujian. Their mean annual gastric cancer mortality has been approximately 7.5 and 75/100 000 population, respectively, since the beginning of the last decade. The aim of this study was to evaluate if H. pylori prevalence bears any relationship to gastric cancer mortality rates in these two southern regions of China.

Helicobacter pylori and upper gastrointestinal symptoms in bronchiectasis.

The recently reported increase in seroprevalence of Helicobacter pylori, the causative pathogen in peptic ulceration, in bronchiectasis is unexplained. Therefore, the association of antibodies directed against cytotoxin-associated gene A(CagA), whose expression indicates virulence of H. pylori, and upper gastrointestinal symptoms in patients with stable bronchiectasis and healthy volunteers evaluated. One hundred patients (mean +/- SD age 55.1+/-16.7 yrs) and 94 healthy asymptomatic subjects (54.6+/-7.6 yrs) underwent clinical and physiological assessment and serum levels of anti-H. pylori CagA were determined using standard clinical and enzyme-linked immunosorbent assay techniques. Samples were positive for anti-H. pylori CagA in 11.7% of controls and 24% of bronchiectatic subjects (p = 0.03). There was, however, no association between serum H. pylori CagA immunoglobulin G level and forced expiratory volume in one second (FEV1), forced vital capacity (FVC), sputum volume, respiratory symptoms or upper respiratory gastrointestinal symptoms (p>0.05). Patients who suffered from acid regurgitation or upper abdominal distension had significantly lower FEV1 and FVC (as a percentage of the predicted value) compared to their counterparts. The results of anticytotoxin-associated gene A measurements in this study contrasted with the previous finding that anti-Helicobacter pylori immunoglobulin G correlated with sputum volume. These findings, therefore, suggest that Helicobacter pylori, should it have a pathogenic role in bronchiectasis, could act via noncytotoxin-associated gene A-mediated mechanisms, and, in this context, gastro-oesophageal reflux might be of importance in bronchiectasis.

Antisense targeting protein kinase Cα and β1 inhibits gastric carcinogenesis

Protein kinase C (PKC) family, which functions through serine/threonine kinase activity, is involved in signal transduction pathways necessary for cell proliferation, differentiation, and apoptosis. Its critical role in neoplastic transformation and tumor invasion renders PKC a potential target for anticancer therapy. In this study, we investigated the effect of targeting individual PKCs on gastric carcinogenesis. We established gastric cancer cell lines stably expressing antisense PKCα, PKCβ1, and PKCβ2 cDNA. These stable transfectants were characterized by cell morphology, cell growth, apoptosis, and tumorigenicity in vitro and in vivo. PKCα-AS and PKCβ1-AS transfectants showed a different morphology with flattened, long processes and decreased nuclear:cytoplasmic ratio compared with the control cells. Cell growth was markedly inhibited in PKCα-AS and PKCβ1-AS transfectants. PKCα-AS and PKCβ1-AS cells were more responsive to mitomycin C- or 5-fluorouracil-induced apoptosis. However, antisense targeting of PKCβ2 did not have any significant effect on cell morphology, cell growth, or apoptosis. Furthermore, antisense inhibition of PKCα and PKCβ1 markedly suppressed colony-forming efficiency in soft agar and in nude mice xenografts. Inhibition of PKCα or PKCβ1 significantly suppressed transcriptional and DNA binding activity of activator protein in gastric cancer cells, suggesting that PKCα or PKCβ1 exerts their effects on cell growth through regulation of activator protein activity. These data provide evidence that targeting PKCα and PKCβ1 by antisense method is a promising therapy for gastric cancer.

Patients with coronary artery disease are at high risk for developing colorectal cancer and adenoma: an interim analysis of a prospective study

Aims: Artificial neural networks (ANN) are computer programs used to identify complexrelations within data that cannot be detected with conventional linear-statistical analysis.The routine clinical predictions of need for lower gastrointestinal endoscopy have beenbased on population statistics with little meaning for individual patient. This results in largenumber of unnecessary colonoscopies. We aimed to develop a neural network algorithmwhich can accurately predict presence of pathology in patients attending routine outpatientclinics. Methods: 300 patients undergoing lower gastrointestinal endoscopy prospectivelycompleted a specifically developed questionnaire which included 40 variables based onclinical symptoms, signs, past and family history. Complete data sets of 50 percent of serieswere used to train the artificial neural network; the remaining 50 percent were used forinternal validation. The primary output used was a positive finding on the colonoscopy,including polyps, cancer, diverticular disease or colitis. Results: The outcome and pathologyreports of all the patients were obtained and assessed. Clear correlation between actual datavalue and artificial neural network value were found (r = 0.931; P = 0.0001). The predictiveaccuracy of neural network was 95% in the training group and was 89% (95% CI 84-96)in the validation set. This accuracy was significantly higher than the clinical accuracy (69%).Conclusions: We have shown that ANN is more accurate than standard statistics whenapplied to prediction in individual patients of need for lower gastrointestinal endoscopy.These results have obvious implications, with at least 20% resultant decrease in need forunnecessary lower gastrointestinal endoscopy. The logistic and economic impact with thisdevelopment is tremendous.Andrea M. Harrington, Margaret Lee, Sim-Yee Ong, Eric Yong, Pam Farmer, John M. Hutson and Bridget R. Southwell

CagA positive strains increase the risk of gastric cancer in Hong Kong with moderate prevalence of Helicobacter pylori infection and gastric cancer mortality

This journal suppl. entitled: The American Gastroenterological Association and Digestive Disease Week

Eradication of Helicobacter pylori for prevention of gastric cancer

Endoscopy used to be organised and performed on a personal basis by enthusiastic individuals with a particular interest in the technique. Today the provision of a safe, effective and well-run endoscopy service is an essential part of every general hospital and clinic that provides a gastrointestinal service. Its organisation requires the skills, knowledge and experience that involve a wide range of professional talents and personnel. The role of the Endoscopy Director however remains critical in ensuring that patients receive the best care that is possible. This workshop that is designed for endoscopy Directors and those who hope to take on this role in the future is a continuation of a series of workshops that WEO and the A-PSDE have organised at A-PDW over the past four years. Whereas previously we have adopted a general approach to the responsibilities of the endoscopy director, on this occasion we will focus on Quality Assurance in endoscopy. As with previous years we will adopt an informal and interactive approach to the programme. We are delighted to have recruited an International Faculty with experience in each of the main endoscopic specialties and who have a particular interest in Quality issues. More importantly, we have involved well-known opinion leaders in Thailand who understand the particular challenges that confront endoscopy services in the Asian arena. The ability of an endoscopy unit to audit and record their successes and to identify their diffi culties is essential if they are to provide a safe and effective service and one that is able year by year to improve its outcomes. This workshop will set out the principles underlying a Quality Assurance Programme that will enable participants to develop their own protocols that will lead to a safer and more effective service. Quality indicators in general endoscopy, colonoscopy and ERCP will be addressed together with issues concerning minimal standards, continuous quality improvement and the management of under-performance. National and International guidelines and the importance of quality in protecting against litigation will be topics for discussion. The workshop programme is set out below and we welcome all those interested in improving their endoscopy service to attend what we believe will be an exciting and valuable learning experience. 6 December 2012 (Thursday) JGHF Okuda Lectureship 8:30–9:10

Helicobacter pylori infection, interleukin 1 beta polymorphism andpredisposition to gastric cancer through the CpG island methylation pathway

Aims: Artificial neural networks (ANN) are computer programs used to identify complexrelations within data that cannot be detected with conventional linear-statistical analysis.The routine clinical predictions of need for lower gastrointestinal endoscopy have beenbased on population statistics with little meaning for individual patient. This results in largenumber of unnecessary colonoscopies. We aimed to develop a neural network algorithmwhich can accurately predict presence of pathology in patients attending routine outpatientclinics. Methods: 300 patients undergoing lower gastrointestinal endoscopy prospectivelycompleted a specifically developed questionnaire which included 40 variables based onclinical symptoms, signs, past and family history. Complete data sets of 50 percent of serieswere used to train the artificial neural network; the remaining 50 percent were used forinternal validation. The primary output used was a positive finding on the colonoscopy,including polyps, cancer, diverticular disease or colitis. Results: The outcome and pathologyreports of all the patients were obtained and assessed. Clear correlation between actual datavalue and artificial neural network value were found (r = 0.931; P = 0.0001). The predictiveaccuracy of neural network was 95% in the training group and was 89% (95% CI 84-96)in the validation set. This accuracy was significantly higher than the clinical accuracy (69%).Conclusions: We have shown that ANN is more accurate than standard statistics whenapplied to prediction in individual patients of need for lower gastrointestinal endoscopy.These results have obvious implications, with at least 20% resultant decrease in need forunnecessary lower gastrointestinal endoscopy. The logistic and economic impact with thisdevelopment is tremendous.Andrea M. Harrington, Margaret Lee, Sim-Yee Ong, Eric Yong, Pam Farmer, John M. Hutson and Bridget R. Southwell

Effects of cyclooxygenase-1 and -2 gene disruption onhelicobacter pylori-induced inflammation, apoptosisand proliferation

Background and objectives Gastroesophageal reflux disease (GERD) is thought to cause or exacerbate pre-existing asthma.Treating GERD in asthma patients with potent acid suppression may therefore result in improvement in asthma control. The aim of this study is to determine the effect of proton-pump inhibitor (PPI) therapy on the severity of asthma. Methods Patients with moderate to severe asthma with or without GERD were prescribed an 8-week course of lansoprazole 30mg daily. A baseline and an ‘end-of-treatment’, one-week pulmonary symptom severity score (PSS), one-week reflux symptom severity score (RSS), peak expiratory flow rate (PEFR) and forced expiratory volume in one second (FEV1) were recorded. Symptoms were assessed by an investigator who was blind to the GERD status of the patient. Efficacy of treatment was assessed by comparison of the pre and post treatment mean scores of the above variables. Results Thirty patients were recruited. 27 patients completed the treatment and were available for analysis (16—GERD, 11—nonGERD). 12 (75%) patients reported improvement in asthma symptoms with a significant reduction in mean PSS (p = 0.002).There was no significant change in the mean PEFR and FEV1 (p = 0.075, p = 0.147 respectively). Amongst the non-GERD patients, the mean PSS did not show significant improvement (p = 0.317). There was also no improvement in the PEFR and FEV1.The change in the mean PSS, PEFR and FEV1 pre and post treatment was significantly higher in GERD vs non-GERD patients.

Aberrant epithelial expression of trefoil family factor 2 and mucin 6 in helicobacter pylori-infected gastric antrum, incisura and body: a useful marker for antralization

Aberrant epithelial expression of trefoil family factor 2 and Mucin 6 in helicobacter pylori-infected gastric antrum, incisura and body—a useful marker for antralization YI YANG, HARRY HUA-XIANG XIA, SHIU KUM LAM, WAI MAN WONG, HESS KWAN LOK CHEUNG, SUET YI LEUNG, SIU TSAN YUEN, GOERGE ELIA, NICHOLAS A WRIGHT, BENJAMIN CHUN YU WONG Departments of Medicine and Pathology,The University of Hong Kong, Queen Mary Hospital, Hong Kong, China and Histopathology Unit, Imperial Cancer Research Fund, London, UK

Methylation of E-cadherin gene in gastric cancer and in normal gastric mucosa from patients with and wihtout Helicobacter pylori infection

This free journal suppl. entitled: Abstracts from the Asia Pacific Digestive Week (APDW 2003)