Review article: the epidemiology and prevention of gastric cancer.

BACKGROUND: Gastric cancer can be divided into cardia and noncardia gastric adenocarcinoma (NCGA). Non cardia gastric cancer is a disease that has declined in global incidence but has remained as an extremely lethal cancer. AIM: To review recent advances in epidemiology and strategies in prevention of non cardia gastric cancer. METHODS: A rapid literature search strategy was developed for all English language literature published before March 2013. The search was conducted using the electronic databases PubMed and EMBASE. The search strategy included the keywords 'stomach neoplasms', 'gastric cancer', 'epidemiology', 'risk factor', 'early detection of cancer', 'mass screening', 'cancer burden', 'prevention' and 'cost-effectiveness'. The search strategy was adjusted according to different requirements for each database. The specific search was also performed in cancer-related websites for country-specific information. The search was limited to past 10 years. RESULTS: Gastric cancer is the fifth most common cancer but the third leading cause of cancer death. The case fatality rate is 75%. Screening by radiological or endoscopic methods has limited success in prevention of gastric cancer. Helicobacter pylori has been identified as a carcinogen, accounting for 60-70% of gastric cancer globally and eradication is a potential preventive measure. A meta-analysis in 2009 demonstrated that individuals treated with H. pylori eradication therapy can reduce gastric cancer risk. The extended Shandong Intervention trial that lasted 14.3 years showed that H. pylori eradication therapy significantly reduced gastric cancer incidence by 39%. Consensus groups from Asia, Europe and Japan have recommended H. pylori eradication as primary prevention in high-risk areas. Following eradication therapy, endoscopic surveillance of pre-malignant lesions using enhanced imaging appears to be another promising preventive strategy. CONCLUSIONS: Gastric cancer remains a major diagnostic and therapeutic challenge. There is emerging evidence that H. pylori eradication in high gastric cancer regions can lead to a decline in the incidence of this highly lethal disease.

Influenza A H1N1 (2009): clinical spectrum of disease among adult patients admitted to a regional hospital in Singapore.

INTRODUCTION: The worldwide spread of Influenza A H1N1 (2009) has proceeded at an unprecedented rate, with the World Health Organization rapidly raising its influenza pandemic alert to phase six. We describe the disease spectrum of H1N1 (2009) to aid the triaging and identification of patients at risk. METHODS: This is a retrospective chart review of all confirmed H1N1 (2009) cases admitted to our institution between June and September 2009. RESULTS: The disease severity of the 153 patients studied was classified as mild (n is 75), moderate (n is 55) and severe (n is 23). 81 patients were female. The median age was 26 years. While comorbidities were more prevalent among patients with moderate-severe illness, 47.4 percent reported no pre-existing illness. Presenting complaints of breathlessness, tachycardia, low-pulse oximetry, higher leukocyte counts and C-reactive protein with low albumin levels were more commonly noted in moderate-severe illness (p-value less than 0.001). All patients received oseltamivir at a median of four days from illness onset. 18 required intensive care unit admission, with the majority (94.4 percent) within the first 24 hours of hospitalisation. The overall mortality rate was 4.6 percent. Median lengths of hospitalisation were four and nine days for moderate and severe cases, respectively. CONCLUSION: While the majority of H1N1 (2009) patients have mild illness, a subgroup can become critically ill. Prior good health is not necessarily a good discriminator against severe illness. The presence of dyspnoea, tachycardia and desaturation at triage should heighten the index of suspicion for H1N1 (2009)-related complications.

Singapore Armed Forces Medical Corps-Ministry of Health clinical practice guidelines: management of heat injury.

The Singapore Armed Forces (SAF) Medical Corps and the Ministry of Health (MOH) have published clinical practice guidelines on Management of Heat Injury to provide doctors and patients in Singapore with evidence-based guidance on the prevention and clinical management of exertional heat injuries. This article reproduces the introduction and executive summary (with recommendations from the guidelines) from the SAF Medical Corps-MOH clinical practice guidelines on Management of Heat Injury, 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=25178. 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.

The cag PAI is intact and functional but HP0521 varies significantly in Helicobacter pylori isolates from Malaysia and Singapore.

Helicobacter pylori-related disease is at least partially attributable to the genotype of the infecting strain, particularly the presence of specific virulence factors. We investigated the prevalence of a novel combination of H. pylori virulence factors, including the cag pathogenicity island (PAI), and their association with severe disease in isolates from the three major ethnicities in Malaysia and Singapore, and evaluated whether the cag PAI was intact and functional in vitro. Polymerase chain reaction (PCR) was used to detect dupA, cagA, cagE, cagT, cagL and babA, and to type vacA, the EPIYA motifs, HP0521 alleles and oipA ON status in 159 H. pylori clinical isolates. Twenty-two strains were investigated for IL-8 induction and CagA translocation in vitro. The prevalence of cagA, cagE, cagL, cagT, babA, oipA ON and vacA s1 and i1 was >85%, irrespective of the disease state or ethnicity. The prevalence of dupA and the predominant HP0521 allele and EPIYA motif varied significantly with ethnicity (p < 0.05). A high prevalence of an intact cag PAI was found in all ethnic groups; however, no association was observed between any virulence factor and disease state. The novel association between the HP0521 alleles, EPIYA motifs and host ethnicity indicates that further studies to determine the function of this gene are important.

Endosonography- vs. endoscopic retrograde cholangiopancreatography-based strategies in the evaluation of suspected common bile duct stones in patients with normal transabdominal imaging.

BACKGROUND: Endosonography (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) are highly accurate techniques for evaluating common bile duct stones. AIM: To compare the clinical impact and costs of EUS- and ERCP-based strategies for evaluating patients with suspected common bile duct stones but normal transabdominal imaging. METHODS: The costs of EUS- vs. ERCP-based strategies were compared in patients with suspected acute biliary obstruction from common bile duct stones but normal transabdominal imaging. RESULTS: Over a 15-month period, 110 patients were recruited. EUS detected a common bile duct lesion in 73% (common bile duct stones: 68%; pancreatic cancer: 2%; ampulla tumour: 2%; cholangiocarcinoma: 1%). The sensitivity, specificity, positive predictive value and negative predictive value of EUS were 98%, 100%, 100% and 93%, respectively. EUS prevented 30% unnecessary ERCP. The mean difference in cost per patient between EUS- and ERCP-based strategies was US$166. When stratified according to clinical indications, an EUS-based strategy was costlier only in suspected biliary sepsis. Costs were similar when the indications were cholestatic jaundice, acute pancreatitis and cholestasis. CONCLUSION: EUS prior to biliary interventions in patients with suspected common bile duct stones prevented unnecessary ERCP. It allowed a definitive diagnosis to be made prior to more invasive procedures.

Endoscopic ultrasound-guided fine needle aspiration in the evaluation of suspected lung cancer.

BACKGROUND AND AIM: The role of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in the diagnosis and staging of lung cancer is still not fully explored. This prospective study aimed to define the effectiveness of EUS-FNA as an adjunct to computer tomography (CT) and bronchoscopy in the evaluation of suspected lung cancer in routine clinical practice. METHODS: Over a period of 20 weeks, the data of 16 consecutive patients suspected of lung cancer on account of respiratory symptoms, and/or the findings of either a mass or mediastinal lymph nodes on helical CT, who were referred for evaluation by EUS, were prospectively collected. Fourteen of these patients underwent sequential bronchoscopy followed by EUS-FNA in the same setting. RESULTS: Bronchoscopy was performed in 15 patients, while EUS was performed in all 16 patients. Bronchoscopy diagnosed 9 cases of non-small-cell lung cancer (NSCLC) but was falsely negative in 3 cases of malignancies, which were all established by EUS-FNA of mediastinal lymph nodes (2 cases of NSCLC and 1 case of esophageal squamous cell cancer). EUS-FNA also diagnosed advanced NSCLC in another patient who did not undergo bronchoscopy, such that eventually 13 patients were diagnosed to have malignancies. Distant metastases were diagnosed by EUS-FNA in 4 cases of NSCLC (2 cases of left adrenal gland and 2 cases of pancreatic metastases). Two patients were diagnosed to have sarcoidosis and 1 patient was diagnosed to have pneumoconiosis eventually. CONCLUSIONS: EUS-FNA is useful as an adjunct to CT and bronchoscopy in the evaluation of suspected lung cancer.

Management consensus of inflammatory bowel disease for the Asia-Pacific region.

At the present there are no large-scale epidemiologic data on inflammatory bowel disease (IBD) in the Asia-Pacific region, but several studies have shown an increased incidence and prevalence of IBD in this region. Compared to the West, there appears to exist a time lag phenomenon. With regard to the two main forms of IBD, ulcerative colitis (UC) is more prevalent than Crohn's disease (CD). In addition to geographic differences, ethnic differences have been observed in the multiracial Asian countries. Moreover, the genetic backgrounds are different in the Asian compared to Western patients. For instance, NOD2/CARD15 variants have not been found in Asian CD patients. In general, the clinical course of IBD seems to be less severe in the Asia-Pacific region than in Western countries. Diagnosis of IBD in this region poses special problems. The lack of a gold standard for the diagnosis of IBD, and the existence of a variety of infectious enterocolitis with similar manifestations to those of IBD make the differential diagnosis particularly difficult. So far, Western diagnostic criteria have been introduced for the diagnosis of IBD. A stepwise approach to exclude non-IBD enterocolitis also must be introduced, and a definite diagnosis must include typical histological features. In some patients, follow up and therapeutic trials might be necessary to obtain a definitive diagnosis. A better understanding of the pathogenesis of IBD will allow the development of better diagnostic markers. The management of IBD also poses some special problems in the Asia-Pacific Region. There is often a delay in using proper medications for IBD, and alternative local remedies are still widely used. With a combination of Western guidelines and regional experiences, similar principles can be used for induction and maintenance of remission. A stepwise selection of medications is advocated depending on the extent, activity and severity of the disease. Comprehensive and individualized approaches are suggested for different IBD patients. Deeper understanding of disease pathogenesis and the unique characteristics of IBD in the Asia-Pacific region, combined with reasonable and practical guidelines for drug management and the future use of biological agents would improve the therapeutic outlook of IBD in this region.

Rabeprazole vs esomeprazole in non-erosive gastro-esophageal reflux disease: a randomized, double-blind study in urban Asia.

AIM: Gastro-esophageal reflux disease (GERD) is becoming increasingly common in Asia. Data on the efficacy of proton pump inhibitors in patients with non-erosive GERD (NERD) in Asia is lacking. This double-blind study compared the efficacy and safety of rabeprazole with esomeprazole in relief of symptoms in patients with NERD. METHODS: One hundred and thirty-four patients with reflux symptoms of NERD and normal endoscopy were randomized to receive rabeprazole 10 mg or esomeprazole 20 mg once daily for 4 wk. Symptoms were recorded in a diary and changes in severity of symptoms noted. RESULTS: At 4 wk of treatment, rabeprazole 10 mg and esomeprazole 20 mg were comparable with regards to the primary endpoint of time to achieve 24-h symptom-free interval for heartburn 8.5 d vs 9 d and regurgitation 6 d vs 7.5 d. Rabeprazole and esomeprazole were also similarly efficacious in term of patient's global evaluation with 96% of patients on rabeprazole and 87.9% of patients on esomeprazole, reporting that symptoms improved (P = NS). Satisfactory relief of day- and night-time symptoms was achieved in 98% of patients receiving rabeprazole and 81.4% of patients receiving esomeprazole. Adverse events were comparable in both groups (P = NS). CONCLUSION: Rabeprazole 10 mg has a similar efficacy and safety profile in Asians with NERD as esomeprazole 20 mg. Further study is necessary to investigate whether the small differences between the two drugs seen in this study are related to the improved pharmacodynamic properties of rabeprazole. Both drugs were well tolerated.

Validation of 13C-urea breathtest for the diagnosis of Helicobacter pylori infection in the Singapore population.

INTRODUCTION: Several tests are available for determining the presence of Helicobacter pylori (H. pylori) infection. These may be invasive or non-invasive. The carbon urea breath test (C-UBT) is generally considered to be a simple, non-invasive and accurate test for the detection of H. pylori infection both before and after treatment. Commercially available 13C-UBT kits are generally validated in their country of manufacture and the stated accuracy of their tests may not be applicable to our local population. AIM: The aim of our study was to determine the accuracy of a commercial 13C-urea breath test kit, Hp-Plus (Utandningstester i Sverige AB, Sweden), in the Singapore population. PATIENTS AND METHODS: One hundred patients for oesophago-gastro-duodenoscopy (OGD) were recruited into this prospective study. Gastric biopsies were obtained for the biopsy urease test and histological examination. Blood samples were obtained for H. pylori serology. Breath samples were then obtained at baseline and after consumption of 100 mg of labelled 13C-urea. The presence of H. pylori infection was defined by a positive result on any two of the three tests (biopsy urease test, histology, serology) performed for the detection of H. pylori. Using this "gold standard", the sensitivity, specificity, and positive and negative predictive values of the 13C-UBT were calculated. RESULTS: In the Singapore population, the 13C-UBT (Hp plus) has a sensitivity and specificity of 94.2% and 100% respectively for the detection of H. pylori infection. The positive predictive value and negative predictive value of the 13C-UBT is 100% and 88.6% respectively. CONCLUSION: The 13C-UBT is a simple, safe, and accurate non-invasive test for the detection of H. pylori infection, making it a valuable tool in local clinical practice.

Hepatocellular carcinoma: an Asian perspective.

Hepatocellular carcinoma (HCC) is one of the most frequently occurring malignancies in Asia. The incidence exceeds 30 cases/100,000/year in the east Asian region. Worldwide, it accounts for almost 1 million deaths/year. The high incidence in Asia is due to the high prevalence of chronic viral hepatitis, mainly chronic hepatitis B. With the introduction of universal vaccination for hepatitis B in some Asian countries in the mid 1980s, some of these countries are experiencing a decline in the incidence of HCC. This probably underscores the point that HCC caused by hepatitis B is a malignancy preventable by vaccine. Due to the relative paucity of symptoms in the early stages and the rapid doubling time of the tumor, most HCCs are discovered late in advanced stages at presentation. Most Asian countries have adopted a screening program for patients at risk. Earlier and smaller HCCs are detected through such programs but these programs have yet to demonstrate improved patient survival. Physicians managing patients with HCC are faced with two main challenges, the malignancy itself and the underlying liver disease. The extent of the tumor and the existing liver function limits the therapeutic choices available. Hepatic resection remains the treatment of choice. However, the majority of patients present with nonresectable tumors. Transarterial chemoembolization, percutaneous ethanol injection and radiofrequency ablation are the other treatment modalities. In patients with small tumors (<5 cm) and poor liver function, liver transplant offers a viable treatment alternative. In summary, the risk factor for HCC in Asia is predominantly chronic hepatitis B. Universal vaccination against hepatitis B is likely to reduce the incidence. The prognosis and outcome of treatment remains poor with a 5-year survival of 35% for patients treated surgically and less than 10% for nonresectable tumors. Current management is aimed at earlier detection and more effective treatment of early HCC. In future, the challenge will be managing HCC in the premalignant stage.

Psychiatric illness, personality traits and the irritable bowel syndrome.

INTRODUCTION: Irritable bowel syndrome is a common functional gastrointestinal disorder. Although its aetiology is still unknown, visceral hypersensitivity, disorders of motility and psychosocial factors have been proposed as possible factors that affect the "gut-brain" function. The objective of this study was to determine if psychiatric disorders exist in patients with irritable bowel syndrome. PATIENTS AND METHODS: During a 10-month period, 43 outpatients, after exclusion of organic bowel pathology and meeting Manning's criteria for the diagnosis of irritable bowel syndrome, were assessed using the Eysenck Personality Questionnaire. In addition, a psychiatric interview was conducted by two psychiatrists. Twenty patients with organic bowel disorders, who were age matched, were selected as patient control. RESULTS: Psychiatric diagnoses (62.5%) were present in significantly more female patients with irritable bowel syndrome than female patients with organic bowel disorders (16.7%, P < 0.05). On Eysenck Personality testing, female patients with irritable bowel syndrome scored significantly higher on neuroticism (15.25 versus 8.58) and lower on need for social desirability (14.04 versus 17.0) than the organic disease group. Male patients with irritable bowel syndrome were comparable with male patients with organic bowel disorders in terms of presence of minor psychiatric morbidity, psychiatric diagnoses and Eysenck Personality scores. CONCLUSION: There is a difference between male and female patients with irritable bowel syndrome in terms of psychopathology.

The role of spiral computed tomogram in the diagnosis of acute pulmonary embolism.

Acute pulmonary embolism is associated with considerable morbidity and mortality. Early diagnosis and prompt treatment is essential. A number of non-invasive diagnostic tools are available for its detection. However, each one of these tests has its limitations and the invasive pulmonary angiography remains the gold standard. We describe the use of spiral volumetric computerised tomogram in the diagnosis of acute pulmonary embolism in six patients in our centre where ventilation-perfusion scan facility is not available. This safe, simple and non-invasive test has an excellent sensitivity and specificity for the detection of central and segmental pulmonary embolism and may replace the conventional invasive pulmonary angiography for the diagnosis of pulmonary embolism.

Autoimmune hepatitis in Singapore: a rare syndrome affecting middle-aged women.

BACKGROUND AND AIM: The prevalence of autoimmune hepatitis in Singapore is unknown. Over a period of 7 years, 24 cases were diagnosed in a district general hospital in Singapore (Toa Payoh Hospital) by using the scoring system proposed by the International Autoimmune Hepatitis Group in 1993. The aims of our study were to determine the prevalence of autoimmune hepatitis in Singapore, and to investigate the characteristics and prognosis in the mainly Chinese population. METHODS: The case records of all 24 patients were reviewed, and the following parameters were recorded: age at presentation, sex, symptoms and signs at presentation, past exposure to hepatotoxic drugs, alcohol intake, blood transfusion laboratory and histological tests used to determine autoimmune hepatitis, response to treatment, complications, and survival. RESULTS: The mean age of patients was 57 years old. There was a female-male ratio of 11:1. Forty-two percent of the patients were cirrhotic at presentation. The prevalence of autoimmune hepatitis was four per 100 000, with no significant difference between Chinese, Malay and Indian patients (Odds ratio of 0.38 by the chi-squared test). Eighty-nine percent of the patients responded to treatment with the induction of prednisolone, but the relapse rate was 61%. Treatment failure occurred in one patient. The mortality rate during the 7 years of follow up was 21%, and all were caused by complications of cirrhosis. The survival at 5 years was 71%, with a standard error of 0.13. CONCLUSION: Autoimmune hepatitis in Singapore is mainly a disease in older women. The response to steroid treatment is good, with a 5-year survival rate of 71%.