Accuracy of endoscopic ultrasound staging of gastric cancer in routine clinical practice in Singapore.

OBJECTIVE: Endoscopic ultrasound has emerged as the leading modality to assess the T and N stage in gastric cancer. This study aimed to assess the accuracy of TN staging by endoscopic ultrasound in routine clinical practice in Singapore. METHODS: Over a period of 7 years, 77 patients (male: 70%; median age 62.8 years) with gastric cancer underwent preoperative staging with endoscopic ultrasound. Fifty-seven patients eventually underwent surgery with tissues available for histopathological staging and comparison. RESULTS: The tumor locations were: cardia: 13; corpus: 20; incisura: 19; antrum: 25. The majority was poorly differentiated (57.1%); 26% were moderately differentiated and 16.9% were well differentiated adenocarcinoma. Compared to pathological staging, the overall accuracy of T staging by endoscopic ultrasound was 77.2% (17.5% under-staged: 5.3% over-staged). The staging accuracy of T1 (92.9%) and T3 (81.8%) was higher than T2 (57.1%) and T4. For N staging, the accuracy of endoscopic ultrasound was 59.6% (26.3% under-staged; 14% over-staged); this was significantly superior to computer tomography (43.9%). CONCLUSION: Endoscopic ultrasound is useful for the T staging of gastric cancer, with an overall accuracy rate of 77%, and up to 93% for T1 lesions. Under-staging may occur due to microscopic tumor infiltration, while over-staging may arise due to inflammatory reactions. The accuracy of N staging is lower at 60%, but could be further improved with the use of fine needle aspiration.

Helicobacter pylori eradication versus prokinetics in the treatment of functional dyspepsia: a randomized, double-blind study.

BACKGROUND: This randomized, double-blind study compared the efficacy of Helicobacter pylori eradication against prokinetics in H. pylori-infected functional dyspepsia patients. METHODS: Patients with moderately severe or severe dyspepsia fulfilling the Rome II criteria were randomized to either H. pylori eradication for 1 week and 6 weeks of placebo prokinetics or 6 weeks of prokinetics and placebo H. pylori eradication in the first week. Symptoms were assessed at baseline and at 6 and 12 months using the Glasgow Dyspepsia Severity Score (GDSS). Global response to treatment was assessed at 12 months. RESULTS: Altogether 130 patients were enrolled (H. pylori eradication, 71; prokinetics, 59). The mean baseline GDSS was 9.3 for the H. pylori eradication group and 8.9 for the prokinetic group. At 6 months, the score was 3.6 and 4.1, respectively, and it remained at 3.5 and 3.8, respectively, at 12 months. With H. pylori eradication, 31.0% had complete symptom resolution (GDSS 0 or 1) at 12 months compared with 23.7% with prokinetics (a nonsignificant difference). At 12 months, global symptomatic improvement was seen in 62.0% of the H. pylori eradication group compared with 67.8% of the prokinetics group. CONCLUSIONS: Both H. pylori eradication and prokinetic therapy resulted in symptom improvement in two-thirds of dyspeptic patients at 1 year. More patients tended to achieve complete symptom relief with H. pylori eradication.

Randomized, double-blind study of emtricitabine (FTC) plus clevudine versus FTC alone in treatment of chronic hepatitis B.

Emtricitabine (FTC) is approved for the treatment of human immunodeficiency virus. FTC and clevudine (CLV) have activity against hepatitis B virus (HBV). This report summarizes the results of a double-blind, multicenter study of patients with chronic hepatitis B who had completed a phase 3 study of FTC and were randomized 1:1 to 200 mg FTC once daily (QD) plus 10 mg CLV QD or 200 mg FTC QD plus placebo for 24 weeks with 24 weeks of follow-up. One hundred sixty-three patients were treated (82 with FTC plus CLV [FTC+CLV] and 81 with FTC); 72% were men, 53% were Asian, 47% were Caucasian, and 52% were hepatitis B e antigen positive, and the median baseline HBV DNA level was 6 log(10) copies/ml. After 24 weeks of treatment, 74% (FTC+CLV) versus 65% (FTC alone) had serum HBV DNA levels of <4,700 copies/ml (P = 0.114) (Digene HBV Hybrid Capture II assay). Twenty-four weeks posttreatment, the mean change in serum HBV DNA levels from baseline was -1.25 log(10) copies/ml (FTC+CLV), 40% had undetectable viremia (versus 23% for FTC alone), and 63% had normal alanine aminotransferase levels (versus 42% for FTC alone) (P < or = 0.025 for all endpoints). The safety profile was similar between arms during treatment, with less posttreatment exacerbation of hepatitis B in the combination arm. In summary, after 24 weeks of treatment, no significant difference between arms was observed, but there was a significantly greater virologic and biochemical response 24 weeks posttreatment in the FTC+CLV arm.

A double-blind placebo-controlled study of emtricitabine in chronic hepatitis B.

BACKGROUND: Emtricitabine is a nucleoside analogue approved for treatment of human immunodeficiency virus 1 with clinical activity against hepatitis B virus (HBV). METHODS: To compare the safety and efficacy of emtricitabine with placebo in patients with HBV, we conducted a randomized (2:1), double-blind study at 34 sites in North America, Asia, and Europe that enrolled adults between November 2000 and July 2002 who had chronic HBV infection but had never been exposed to nucleoside or nucleotide treatment. Each patient received either 200 mg of emtricitabine (n=167) or placebo (n=81) once daily for 48 weeks and underwent a pretreatment and end-of-treatment liver biopsy. Histologic improvement was defined as a 2-point reduction in Knodell necroinflammatory score with no worsening in fibrosis. RESULTS: At the end of treatment, 103 (62%) of 167 patients receiving active treatment had improved liver histologic findings vs 20 (25%) of 81 receiving placebo (P<.001), with significance demonstrated in subgroups positive (P<.001) and negative (P=.002) for hepatitis Be (HBe) antigen. Serum HBV DNA readings showed less than 400 copies/mL in 91 (54%) of 167 patients in the emtricitabine group vs 2 (2%) of 81 in the placebo group (P<.001); alanine aminotransferase levels were normal in 65% (109/167) vs 25% (20/81), respectively (P<.001). At week 48, 20 (13%) of 159 patients in the emtricitabine group with HBV DNA measured at the end of treatment had detectable virus with resistance mutations (95% confidence interval, 8%-18%). The rate of seroconversion to anti-HBe (12%) and HBe antigen loss were not different between arms. The safety profile of emtricitabine during treatment was similar to that of placebo. Posttreatment exacerbation of HBV infection developed in 23% of emtricitabine-treated patients. CONCLUSION: In patients with chronic HBV, both positive and negative for HBe antigen, 48 weeks of emtricitabine treatment resulted in significant histologic, virologic, and biochemical improvement.

A comparison of the clinical, demographic and psychiatric profiles among patients with erosive and non-erosive reflux disease in a multi-ethnic Asian country.

AIM: To examine the clinical spectrum of gastroesophageal reflux disease (GERD) and compare erosive (ERD) with non-erosive (NERD) in terms of clinical, demographic and psychiatric profiles. METHODS: Patients with reflux symptoms were enrolled and stratified to NERD and ERD after endoscopy (LA classification). Patients with ERD presenting with dyspepsia were included. Patients on proton pump inhibitors (PPI) or H2 receptor antagonists before endoscopy were excluded. Demographic data, Helicobacter pylori (H pylori) status and presence of minor psychiatric morbidity (based on General Health Questionnaire-28) were analyzed. RESULTS: Among 690 patients screened, 533 were eligible for analysis (male to female ratio: 3:2; Chinese: 75.4%; Malay: 9.8%; Indian: 14.8%). Clinical spectrum of GERD: N: 40.5%; A: 46%; B: 9.2%; C: 2.1%; D: 0.6%; Barrett's esophagus: 1.7%. Compared to patients with NERD, patients with ERD were significantly older (45 vs 39.4 years), more likely to be male (64.4% vs 53.7%), tended to smoke (19.6% vs 9.7%), less likely to have minor psychiatric morbidity (26.4 vs 46.7%) and were more likely to respond to PPI (79.7 vs 66.8%). There was also a trend towards a higher BMI (24.5 vs 23.5). Race, alcohol consumption and H pylori status were not significant. On multivariate analysis, age and presence of minor psychiatric morbidity remained with significant differences. CONCLUSION: The majority of patients who have typical symptoms of GERD have NERD or mild erosive reflux disease. Compared to patients with erosive reflux disease, patients with NERD were younger and had a higher prevalence of minor psychiatric morbidity.

Epinephrine injection therapy versus a combination of epinephrine injection and endoscopic hemoclip in the treatment of bleeding ulcers.

AIM: To assess the efficacy of hemoclip application in combination with epinephrine injection in the treatment of bleeding peptic ulcers and to compare the clinical outcomes between patients treated with such a combination therapy and those treated with epinephrine injection alone. METHODS: A total of 293 patients (211 males, 82 females) underwent endoscopic therapy for bleeding peptic ulcers. Of these, 202 patients (152 males, 50 females) received epinephrine injection therapy while 91 patients (59 males, 32 females) received combination therapy. The choice of endoscopic therapy was made by the endoscopist. Hemostatic rates, rebleeding rates, need for emergency surgery and 30-d mortality were the outcome measures studied. RESULTS: Patients who received combination therapy were significantly older (mean age 66+/-16 years, range 24-90 years) and more suffered from chronic renal failure compared to those who received epinephrine injection therapy alone (mean age 61+/-17 years, range 21-89 years). Failure to achieve permanent hemostasis was 4% in the group who received epinephrine injection alone and 11% in the group who received combination therapy. When the differences in age and renal function between the two treatment groups were taken into account by multivariate analysis, the rates of initial hemostasis, rebleeding rates, need for surgery and 30-d mortality for both treatment options were not significantly different. CONCLUSION: Combination therapy of epinephrine injection with endoscopic hemoclip application is an effective method of achieving hemostasis in bleeding peptic ulcer diseases. However, superiority of combination therapy over epinephrine injection alone, could not be demonstrated.

Clinical utility, safety and tolerability of capsule endoscopy in urban Southeast Asian population.

AIM: Capsule endoscopy has demonstrated its clinical utility in the evaluation of small bowel pathology in several Western studies. In this prospective study, we aimed to determine the clinical utility, safety and tolerability of capsule endoscopy in the evaluation of suspected small bowel disease in an urban Southeast Asian population. METHODS: We used the given (M2A) capsule endoscopy system in 16 consecutive patients with suspected small bowel pathology. In 9 patients the indication was obscure gastrointestinal bleeding, while in 6 patients it was to determine the extent of small bowel involvement in Crohn's disease. One patient underwent capsule endoscopy for evaluation of chronic abdominal pain. Patient's tolerability to the procedure was evaluated by standardized questionnaires and all patients were reviewed at one week to ensure that the capsule had been excreted without any adverse events. RESULTS: Abnormal findings were present in 8 patients (50%). The cause of obscure gastrointestinal bleeding was determined in 5 out of 9 patients. Findings included 2 cases of angiodysplasia, 2 cases of jejunal ulcers and 1 case of both angiodysplasia and jejunal ulcer. One patient had small bowel erosions and foci of erythema of doubtful significance. Ileal lesions were diagnosed in 2 out of 6 patients with Crohn's disease. Capsule endoscopy was well tolerated by all patients. One patient with Crohn's disease had a complication of capsule retention due to terminal ileum stricture. The capsule eventually passed out spontaneously after 1 month. CONCLUSION: Our study, which represented the first Asian series, further confirms the diagnostic utility, safety and tolerability of wireless capsule endoscopy.

Clinical profile of primary sclerosing cholangitis in Singapore.

BACKGROUND AND AIM: Primary sclerosing cholangitis (PSC) is a rare chronic disease in Singapore and its epidemiological profile has not been described previously. The present study aimed to define the demographic and clinical profile of patients with PSC in Singapore. METHODS: The case records of patients with PSC seen at Changi General Hospital were analyzed in terms of demographic profile, clinical presentation, clinical course, treatment and complications. RESULTS: Ten cases of PSC were diagnosed over a 10-year period. The male:female ratio was 9:1. The median age of diagnosis was 49.5 years (mean: 50.9 years; range: 35-63 years). With regards to clinical presentation, seven patients had hepatobiliary sepsis, two patients had asymptomatic liver biochemistry abnormalities while one patient had cholestatic jaundice. Prevalence rate of perinuclear antineutrophil cytoplasmic antibody (pANCA) was 20%. Symptomatic inflammatory bowel disease (IBD) was diagnosed in 20% of PSC cases. Eight patients (80%) had intrahepatic ductal involvement while two patients (20%) had combined intrahepatic and extrahepatic ductal involvement on endoscopic retrograde cholangiopancreatography (ERCP). The prevalence rate of recurrent cholangitis was 30% while that of recurrent liver abscess, cirrhosis and common bile duct stricture were all 10%. The mean duration of follow up was 6.6 years with one death from liver failure. CONCLUSION: The clinical profile of patients with PSC in Singapore appears to differ with other published data, with a greater number presenting with hepatobiliary sepsis and less frequent association with IBD and pANCA. It is hypothesized that this may be related to differences in environmental triggers and genetic susceptibility.

Seroreactivity to 19.5-kDa antigen in combination with absence of seroreactivity to 35-kDa antigen is associated with an increased risk of gastric adenocarcinoma.

BACKGROUND: Only a minority of those infected with Helicobacter pylori will develop gastric cancer. Stratification of H. pylori strains based on carcinogenic potential will provide a basis for selective surveillance and eradication therapy. We studied the anti-H. pylori antibody profile in Asian patients with gastric adenocarcinoma to identify any H. pylori antigen that may be associated with an increased or decreased risk of gastric carcinoma. PATIENTS AND METHODS: A case-control study comparing the seroprevalence of antibodies with various H. pylori antigens in Singaporeans with gastric adenocarcinoma and the normal Singaporean population was carried out using both conventional immunoglobulin (Ig) G enzyme-linked immunosorbent assay (ELISA) and Western blot immunoassay. RESULTS: The seroprevalence among 44 gastric adenocarcinoma cases (70.5% males, mean age 66.7 +/- 13.5 years) and 261 controls (49.8% males, mean age 61.5 +/- 4.1 years) was 90.9% vs. 50.2% by IgG ELISA. In the H. pylori-positive male population, those suffering from gastric adenocarcinoma had significantly lower seroreactivity to the 35-kDa antigen compared with asymptomatic controls (p =.0198, OR = 3.79, 95% CI 1.24-11.61). Seropositivity to the 19.5 kDa antigen was also found to be associated with the presence of gastric adenocarcinoma in Singaporean males (p =.022, OR = 4.17, 95% CI 1.22-14.28). A 'high-risk' phenotype consisting of absence of a band at 35-kDa in combination with the presence of a band at 19.5-kDa was significantly associated with the presence of gastric adenocarcinoma (p =.002, OR = 3.7, 95% CI 1.6-8.6). CONCLUSIONS: Stratification of H. pylori strains based on their potential for carcinogenesis, such as those strains that are seropositive for the 19.5 kDa antigen and seronegative for the 35-kDa antigen, may provide a basis for selective eradication of H. pylori infection and future vaccine development.