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.

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.

Triple therapy in the eradication of Helicobacter pylori in patients with duodenal ulcer disease: results of a multicentre study in South-East Asia. South-East Asia Multicenter Study Group.

BACKGROUND: The efficacy of proton pump inhibitor based triple therapy in patients from South-East Asia, where metronidazole resistance is reportedly high, has not been formally assessed in randomized, multicentre trials. AIM: To compare the eradication rates of Helicobacter pylori, ulcer healing rates and side-effects of three regimens of omeprazole triple therapy in patients with duodenal ulcer from South-East Asia and to study the impact of metronidazole resistance. METHODS: A single blind, randomized parallel group, comparative multicentre study. A total of 246 patients from 15 centres in four South-East Asian countries were randomized to receive OAC (omeprazole 20 mg b.d., amoxycillin 1 g b. d., clarithromycin 500 mg b.d.), OAM (omeprazole 20 mg b.d., amoxycillin 1 g b.d., metronidazole 400 mg b.d.) or OMC (omeprazole 20 mg b.d., metronidazole 400 mg b.d., clarithromycin 500 mg b.d.) for 7 days. After triple therapy, the patients were further randomized to receive either omeprazole or placebo for 7 days. Upper gastrointestinal endoscopy was performed before treatment and 4 weeks after treatment. Biopsies for culture and for histopathological examination for H. pylori were taken from corpus and antrum before treatment and 4 weeks after treatment. RESULTS: The eradication rates were intention-to-treat/per protocol (95% CI): OAC 87% (79-94%)/94% (89-100%); OAM 80% (70-89%)/91% (83-98%); OMC 85% (77-93%)/94% (88-100%). The difference in eradication rates between the three groups was not statistically significant (P=0.419). Pre-treatment metronidazole resistance, was found in 34% of isolates and was a significant prognostic factor in patients receiving OAM (odds ratio 5.26) but not in patients receiving OAC or OMC. CONCLUSIONS: All three treatment regimens were safe, well tolerated and highly effective for eradication of H. pylori and ulcer healing. Pre-treatment metronidazole resistance reduced the efficacy of OAM but did not affect the efficacy of OMC.

Non-steroidal anti-inflammatory drugs, Helicobacter pylori and bleeding gastric ulcer.

BACKGROUND: Helicobacter pylori infection and NSAID usage are considered to be independent risk factors for gastric ulcer (GU). Whether they interact to influence the risk of bleeding in GU is unclear. AIM: To determine the prevalence of H. pylori infection and NSAID ingestion in a group of patients with GU and determine their roles in bleeding and non-bleeding GU. METHODS AND RESULTS: From January 1993 to June 1996, a total of 217 GU patients (150 male, 67 female, median age 61 years, range 26-94) were eligible for the study. Eighty-five per cent were H. pylori-positive and 15% were H. pylori-negative. NSAID usage within 4 weeks prior to endoscopy was present in 30%, more in the H. pylori-negative than H. pylori-positive patients (59% vs. 25% P = 0.0002). Aspirin was most commonly used (43%). One hundred patients bled from GU (69 male, 31 female, mean age 67 years, range 26-94) and 117 did not (81 male, 36 female, mean age 57 years, range 28-86). Univariate logistic regression showed that advanced age (>/= 65 years) and NSAID usage carried an increased risk of bleeding GU (odds ratio 3.4 and 6.8, respectively) while H. pylori infection alone was not associated with additional risk (OR = 0.8). However, when three variables were considered jointly in a multiple logistic regression, the OR associated with H. pylori infection increased to 2.4, suggesting that in the presence of NSAIDs and advanced age, H. pylori also increases the risk of bleeding GU, indicating an interaction between the variables. CONCLUSION: NSAID usage and advanced age are risk factors for bleeding GU, whereas H. pylori infection by itself is not. In the presence of NSAIDs and advanced age, an increased risk of bleeding GU with H. pylori is observed, indicating the possibility of an interaction between these factors.

Comparison of lansoprazole-based triple and dual therapy for treatment of Helicobacter pylori-related duodenal ulcer: an Asian multicentre double-blind randomized placebo controlled study.

BACKGROUND: [corrected] In Asian countries with limited resources, clarithromycin-based triple therapy may not be readily available. There are also few direct comparisons of different regimens in Asia. AIM: To compare two lansoprazole-based non-clarithromycin triple therapies and one dual therapy in a prospective double-blind placebo-controlled study of Helicobacter pylori eradication and duodenal ulcer healing. METHODS: Fourteen centres in Asia participated in this study. Patients with acute duodenal ulcer who were H. pylori-positive were recruited. They were randomized to receive: (a) lansoprazole 30 mg b.d., amoxycillin 1 g b.d. and metronidazole 500 mg b.d. for 2 weeks (LAM-2 W), or (b) LAM for 1 week and placebo (LAM-1 W), or (c) lansoprazole 30 mg b.d., amoxycillin 1 g b.d. and placebo for 2 weeks (LA-2 W). Upper endoscopy was repeated at week 6 to check for duodenal ulcer healing. Symptoms and side-effects were recorded. RESULTS: A total of 228 patients were recruited, and two patients took less than 50% of the drugs. H. pylori eradication rates (intention-to-treat) were 68 out of 82 (83%) with LAM-2 W, 55 out of 71 (78%) with LAM-1 W and 43 out of 75 (57%) with LA-2 W. There were significant differences (P=0. 001) in eradication rates when comparing either LAM-2 W or LAM-1 W with LA-2 W. The eradication rate in patients with metronidazole resistant H. pylori strains were significantly lower than those with metronidazole sensitive strains (P=0.0001). The duodenal ulcer healing rates at week 6 were 85%, 85% and 72% in LAM-2 W, LAM-1 W and LA-2 W, respectively (P=0.065). Side-effects occurred in 13%, 11% and 9% in LAM-2 W, LAM-1 W and LA-2 W, respectively. H. pylori eradication and initial ulcer size were factors affecting duodenal ulcer healing. CONCLUSIONS: This Asian multicentre study showed that 1-week lansoprazole-based triple therapy without clarithromycin has similar efficacy in H. pylori eradication and ulcer healing compared with a 2-week regimen. Both triple therapies were significantly better than dual therapy in H. pylori eradication. Therefore, 1-week lansoprazole-based triple therapy is as safe and effective as 2-week therapy in eradication of H. pylori infection and healing of duodenal ulcer in these Asian centres.

Early gastric cancer: 52 cases of combined experience of two south Australian teaching hospitals.

Fifty-two patients with early gastric cancer are described. At presentation, the average age was 60 years and the male:female ratio was 3:2. The patients had presenting symptoms indistinguishable from those due to benign peptic ulcer disease. Endoscopic examination with multiple biopsies was the most accurate means of diagnosis, with an overall 93% detection rate. The tumours were located predominantly along the lesser curve (75%) and in the antrum (64%), with ulcerated or depressed lesions most common and flat lesions least common. Approximately 58% of lesions were of intestinal type, submucosal invasion was seen in 45% and lymph node metastases had occurred in 7% of cases. Lesser curve and antral lesions were more likely to be ulcerated. Ulcerated lesions were on average, the same size as non-ulcerated lesions. Body lesions were larger than antral lesions and lesions which had spread to the submucosa were larger than mucosal lesions. Diffuse-type lesions were more likely to be ulcerated than intestinal-type lesions and dysplasia was more commonly associated with intestinal-type lesions than with diffuse or mixed-type lesions. The crude 5-year survival rate was 80%, but only one death was associated with a recurrence of gastric cancer.

Endoscopic adrenaline injection in treatment of bleeding peptic ulcers.

This study aimed to compare the results of bleeding peptic ulcer treated by endoscopic adrenaline injection with controls treated conventionally. Between January 1991 and December 1993, 69 patients with actively bleeding peptic ulcers with visible vessel received endoscopic adrenaline injection. This group of patients was compared with 31 endoscopically similar patients treated conventionally, using H2 blockers with or without surgery, from October 1987 to December 1990 prior to the introduction of endoscopic injection therapy in this hospital. Both groups of patients were comparable in terms of age, haemoglobin level on admission and site of ulcer (gastric or duodenal). Permanent haemostasis was attained with endoscopic adrenaline injection in 97% of our patients. Rebleeding occurred in 9% in the injected group vs 39% in the historical control group (p < 0.005). Three percent of patients in the injected group had emergency surgery compared with 48% in the control group (p < 0.005). The median hospital stay and transfusion requirements in the injected group were 6 days and 2 units respectively vs 8 days and 3 units in the control group but the difference was not statistically significant. We conclude that endoscopic adrenaline injection is effective in the treatment of bleeding peptic ulcer leading to a reduction in rebleeding rate and emergency surgery.

Heat stroke: a clinical review of 27 cases.

Heat stroke is the most serious entity amongst the heat disorders. Whilst potentially fatal, it is preventable and salvageable. A retrospective study involving 27 patients admitted for exertional heat stroke to the Medical Unit, Toa Payoh Hospital, Singapore from January, 1984 to January, 1987 was carried out. These patients presented with a rectal temperature of greater than 40 degrees C and central nervous system disturbances. All were males and, except for three, were local born. All except two were below thirty years old. The patients were treated with a standard regime of IV fluids and sponging in the ICU. 19 patients (70.4%) presented in coma whilst abnormal behaviour, e.g. aggression and mental confusion was seen in the remainder. Fits were seen in only 5 patients (18.5%). Metabolic acidosis was seen in 93.3%. Hypokalaemia was present in 3 patients (11.1%). Of the enzymes, creatinine phosphokinase was elevated in all except 1 patient (mean: 4868.8, range: 146-28850). There were no deaths recorded in this series. Complications include reversible DIVC (3 instances), oliguric renal failure (4 instances) and residual neurological deficit (2 instances). 9 patients (39.1%) took more than 4 hours for the rectal temperature to attain 37.5 degrees C. All the above complications except for 1 instance of DIVC occurred in this group with delayed cooling. Heat stroke is a serious condition with serious complications and require prompt treatment.

Four year experience with cholangiocarcinoma: a survey of patients, clinical presentation, management and prognosis in two hospitals.

Seventeen patients with cholangiocarcinoma diagnosed in Toa Payoh and Tan Tock Seng Hospitals from 1986-90 were studied retrospectively. There was a male preponderance (male:female = 12:5) with a mean age of 58 years (range 28-82 years). All presented with obstructive jaundice. Three had cholangitis. Biliary stones were associated in 3 (18%). Two patients (12%) had choledochal cysts. The level of obstruction was identified at the hilum in 12 (70.5%), lower third in 4 (23.5%) and at a choledochojejunostomy anastomosis in 1 (6%). Ultrasound and percutaneous cholangiography (PTC) were the commonest investigations used. Endoscopic retrograde cholangio-pancreatography (ERCP) was performed in 7 (41%) and computer tomography (CT) of abdomen in 6 (35%). Biochemically, a raised alkaline phosphatase (1.5-9 x normal) was typical. Biliary bypass surgery was performed in 7 (41%); Whipple's procedure in 2 (12%) and drainage only in 6 (35%). Nine operated upon survived an average of 6 months (range 2-11 months) and six by drainage survived an average of 62 days (range 13-155 days). Three (of which two declined treatment) were lost to follow up. Cholangiocarcinoma is an uncommon cancer occurring in the older age group. In younger patients, choledochal cyst seems to be an association. Survival is dismal with palliative treatment.

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.

The value of MRI in the diagnosis and management of neurocysticercosis.

The clinical manifestation of neurocysticercosis is quite protean and variable making it the 'great imitator' of almost any neurological disorder. In the last decade, developments in diagnostic imaging and effective anticysticercus drug therapy have changed the outlook of the disease. Two cases investigated with CT scan and MRI are reported here. One case was treated effectively with antihelminthic therapy. In both cases MRI was found to be much more sensitive than CT scan in picking up the multiple cystic lesions. In addition, 'protoscoleces' and 'differential ring enhancements' not apparent in CT scan were well shown in MRI hence enabling the demonstration of different activity stages. In the treated patient, repeat MRI showed degeneration of the cyst. These illustrate that MRI is superior to CT scan in both the diagnosis and management of the illness.

A randomised trial of amoxycillin versus clarithromycin in combination with omeprazole for eradication of Helicobacter pylori infection in Singapore.

Dual therapy has been reported to produce H.pylori eradication rate of 75-80%. This study is designed to determine the efficacy of omeprazole 20 mg bd in combination with amoxycillin 500 mg tid (Group A), amoxycillin 750 mg tds (Group B) and clarithromycin 500 mg tid (Group C) in Singapore. One hundred and forty-eight patients with H. pylori positive duodenal ulcers between ages of 22 and 69 were enrolled from two centres. There were 48 patients in Group A, 50 patients in Group B and 50 patients in Group C. The medication was given for 14 days. The patients were re-evaluated with an upper GI endoscope 4 weeks after cessation of treatment Successful eradication was defined as H.pylori negative on histology and culture. Based on intention to treat analysis, the eradication rate was 47.8% in Group A, 68% in Group B and 66% in Group C. The difference between GroupA and B were statistically significant (p = 0.04). Based on all patient treated analysis, the eradication rate was 57.5% in Group A, 70.7% in Group B and 75% in Group C. The difference in eradication rates was not statistically significant. Adverse events were reported in 21% of all patients with no difference in the adverse event rate between all groups. The eradication rate achieved with dual therapy in this study was similar to that attained in Western population. Higher dose amoxycillin regime gives a significantly higher eradication than a lower dose amoxycillin.

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.

Working party report of the Gastroenterological Society of Singapore. Part II--Helicobacter pylori and non-ulcer dyspepsia in Singapore.

Non-ulcer dyspepsia (NUD) is a common symptom whose cause is currently unclear. Helicobacter pylori (H pylori) infection is found in half of all patients with NUD but other pathophysiological abnormalities eg delayed gastric emptying, have also been described. NUD patients with or without H pylori infection have identical symptom patterns and pathophysiological parameters. Studies on the efficacy of H pylori treatment in NUD give equivocal results to date. We therefore do not recommend treatment for H pylori in NUD.

Working Party report of the Gastroenterological Society of Singapore. Part I--Helicobacter pylori and peptic ulcer disease in Singapore.

The Gastroenterological Society Working Party on Helicobacter pylori (H pylori) recommends eradication of H pylori in patients with peptic ulcer, provided H pylori infection has been demonstrated. H pylori treatment is not indicated for non-ulcer dyspepsia, histological gastritis or mere demonstration of H pylori infection. H pylori infection can be demonstrated by a urease test, culture or histological assessment on gastric antral biopsy or by a 13C and 14C urea breath test: serology is acceptable if validated in the local population. There are many eradication regimens for H pylori infection and follow-up assessments to demonstrate eradication is desirable.

Hepatitis B virus infection in patients with systemic lupus erythematosus.

Sera from 76 patients with systemic lupus erythematosus (SLE) were examined for HBsAg, anti-HBsAb and total anti-HBcAB by radioimmunoassay. Fifteen patients (19.7%) had one or more of these serological markers of HBV infection. This is comparable to the sero-prevalence in 100 sex- and age-matched healthy individuals (19%). There was no significant difference in the prevalence of HBV infection in patients who had received immunosuppressants compared with those who had not. Patients who had received transfusion of blood or blood products had a higher prevalence of serological markers but this was not statistically significant.