Efficacy of tegaserod for functional constipation in Chinese subjects: a randomized double-blind controlled trial in a single centre.

BACKGROUND: Tegaserod has been shown to be effective in chronic constipation in Western population. Aim We investigated if tegaserod is equally effective in Chinese population. MATERIALS AND METHODS: Two hundred and fifty patients were randomized to a double-blinded 8-week treatment of tegaserod 6 mg b.d. or placebo. Response during weeks 1-4 was defined as an increase in complete spontaneous bowel motion >/=1/week. Secondary efficacy included response during weeks 1-8, individual symptoms and scores, quality of life and global assessment of bowel habits and constipation. RESULTS: One hundred and nine patients from the treatment group and 107 from the placebo group completed the 8-week treatment. Responder rates was 47.7% vs. 29% for the treatment and placebo groups (P = 0.005). The sustained complete spontaneous bowel motion rate was 29.4% vs. 15.7% in the two groups (P = 0.016). The response rates were higher than that reported previously in the Caucasian studies. There was improvement in the scores for stool form scale, bothersomeness of constipation, abdominal distension/bloating and satisfaction of bowel habit (P < 0.05). The mental score was higher in the treatment group (46.8 +/- 9 vs. 43.6 +/- 10, P = 0.01). CONCLUSIONS: Tegaserod is effective in relieving chronic constipation in Chinese population. The efficacy observed may be higher than that in Western population.

Clinical trial: levofloxacin-based quadruple therapy was inferior to traditional quadruple therapy in the treatment of resistant Helicobacter pylori infection.

BACKGROUND: The efficacy of levofloxacin-based quadruple therapy in resistant Helicobacter pylori infection is not known. AIM: To test the efficacy of levofloxacin-based quadruple therapy and traditional quadruple therapy in resistant H. pylori infection. METHODS: One hundred and two patients with resistant H. pylori infection were randomized to 1 week of either EBAL (esomeprazole 40 mg b.d., bismuth subcitrate 240 mg b.d., amoxicillin 1 g b.d. and levofloxacin 500 mg b.d.) or EBMT (esomeprazole 40 mg b.d., bismuth subcitrate 240 mg b.d., metronidazole 400 mg t.d.s. and tetracycline 500 mg q.d.s.). (13)C-urea breath test was performed at week 12 to assess post-treatment H. pylori status. RESULTS: In intention-to-treat analysis H. pylori eradication was achieved in 37 of 51 (73%) subjects in EBAL and 45 of 51 (88%) subjects in EBMT groups, respectively (P = 0.046). Per-protocol eradication rates of EBAL and EMBT groups were 78% and 94%, respectively (P = 0.030). The intention-to-treat eradication rate was statistically lower for EBAL than EMBT (56% vs. 90%, P = 0.013) among those who had failed more than one course of eradication therapy. Previous levofloxacin triple therapy did not affect the efficacy of either protocol significantly. CONCLUSIONS: Levofloxacin-based quadruple therapy was inferior to traditional quadruple therapy for resistant H. pylori infection.

Stability of E-cadherin methylation status in gastric mucosa associated with histology changes.

BACKGROUND: We have previously shown reversal of E-cadherin methylation in gastric mucosa from patients with dyspepsia at week 6 after Helicobacter pylori-eradication therapy. But the long-term methylation status of these patients was unknown. AIM: To investigate the methylation status at E-cadherin at year 3 after H. pylori-eradication therapy. METHODS: 35 patients (25 with and 10 without H. pylori eradicated) enrolled in our previous study were recruited into the present study (year 3 analysis). Methylation at E-cadherin was evaluated by methylation-specific polymerase chain reaction method. RESULTS: There was no difference in age and sex distribution in the two groups. Methylation at E-cadherin in patients with H. pylori eradicated at weeks 0, 6 and year 3 were 52%, 20% and 20%, respectively. Concordant methylation status at week 6 and year 3 was 92%. Methylation at E-cadherin in patients without H. pylori at weeks 0, 6 and year 3 were 50%, 60% and 60%, respectively. Concordant methylation status between week 6 and year 3 was 90%. Stability of E-cadherin methylation status was associated with histological changes. No association between E-cadherin methylation status and age was observed. CONCLUSION: The methylation pattern is stable for a long period, thus suggesting the effect of environment on methylation.

Coexistence between colorectal cancer/adenoma and coronary artery disease: results from 1382 patients.

BACKGROUND: Common risk factors exist in colorectal neoplasia (cancer or adenoma) and coronary artery disease. AIM: To investigate in a retrospective study if there is coexistence of the two events in patients > OR =50 years. METHODS: Computer data on colonoscopies performed on symptomatic patients, the corresponding medical record and colonic histology in 1997-2000 were retrieved. History of coronary artery disease was recorded. To adjust for the factors of age and sex, bivariate logistic regression analysis was used to test for coexistence. RESULTS: 1382 patients were recruited. Colorectal neoplasia and history of coronary artery disease were present in 27% (373) and 12% (167) of patients, respectively. The mean age of patients was older in colorectal neoplasia+ (75 +/- 11 vs. 69 +/- 13 years, P < 0.0001) and in coronary artery disease+ (79 +/- 9 vs. 69 +/- 12 years, P < 0.0001) patients. Male was the predominant sex in colorectal neoplasia+: 33% vs. 22% (P < 0.0001), but not in coronary artery disease+ (P = 0.29). Colorectal neoplasia+ patients were more likely to have coronary artery disease+ [21.2% (79/373) vs. 8.8% (89/1098) (P < 0.0001)]. Bivariate logistic regression analysis showed strong association between the two events (OR: 2.12, 95% CI: 1.5, 3.0). CONCLUSION: There is strong coexistence of colorectal neoplasia and coronary artery disease, probably due to exposure to common risk factors.

Lansoprazole, levofloxacin and amoxicillin triple therapy vs. quadruple therapy as second-line treatment of resistant Helicobacter pylori infection.

AIM: To test the efficacy of levofloxacin-based second-line therapy for resistant Helicobacter pylori infection. METHODS: One hundred and six patients who failed H. pylori eradication were randomized to receive (i) lansoprazole 30 mg, amoxicillin 1 g, levofloxacin 500 mg, all given twice daily for 7 days (LAL); or (ii) lansoprazole 30 mg twice daily, metronidazole 400 mg thrice daily, bismuth subcitrate 120 mg and tetracycline 500 mg four times daily for 7 days (quadruple). Post-treatment H. pylori status was determined by (13)C-urea breath test. RESULTS: Intention-to-treat and per-protocol H. pylori eradication rates were 57/60% for the LAL group and 71/76% for the quadruple group respectively. Metronidazole, clarithromycin, amoxicillin and levofloxacin resistance were found in 76%, 71%, 0% and 18% of patients, respectively. Levofloxacin resistance led to treatment failure in the LAL group. For patients with dual resistance to metronidazole and clarithromycin, the eradication rates were 79% in the LAL group (levofloxacin-sensitive) and 65% in the quadruple group (P=0.34). CONCLUSION: Lansoprazole, amoxicillin plus levofloxacin second-line therapy is comparable with quadruple therapy in efficacy. Subjects, especially those with dual resistance to metronidazole and clarithromycin, may consider levofloxacin-based therapy for levofloxacin-sensitive strains.

Validated questionnaire on diagnosis and symptom severity for functional constipation in the Chinese population.

BACKGROUND: Functional constipation is a common problem in clinical practice. No validated questionnaire is available in Chinese. AIM: To develop a validated questionnaire for diagnosis and symptom assessment in functional constipation for the Chinese population. METHODS: One hundred and eleven patients with constipation and 110 healthy controls were presented with a 24-item constipation questionnaire in the Chinese language. Quality of life in constipation patients was assessed by Short Form-36. Polyethylene glycol was prescribed, for 4 weeks, to 20 patients with newly diagnosed constipation. The questionnaire was administered before and 4 weeks after treatment. Concept, content, construct, discriminant validity and reliability of the questionnaire were assessed. RESULTS: Six items were selected by logistic regression to account for most of the differences between controls and constipated patients with a good reproducibility and internal consistency. A cut-off score of > or =5 was determined to discriminate between controls and constipated patients with a sensitivity of 91% and a specificity of 91%. The constipation questionnaire correlated negatively with seven domains of the Short Form-36 and discriminated between constipated patients who reported symptomatic improvement during polyethylene glycol treatment. CONCLUSIONS: The Chinese constipation questionnaire could be used in epidemiological studies to assess the frequency and severity of constipation in patient populations and in interventional studies of constipation.

Trends in the prevalence of peptic ulcer disease and Helicobacter pylori infection in family physician-referred uninvestigated dyspeptic patients in Hong Kong.

BACKGROUND: Peptic ulcer disease is mainly caused by Helicobacter pylori infection and the use of non-steroidal anti-inflammatory drugs. AIM: To investigate the trends in the prevalence of peptic ulcer disease, H. pylori infection and non-steroidal anti-inflammatory drug use in uninvestigated dyspeptic patients over recent years in Hong Kong. METHODS: Data from consecutive patients with uninvestigated dyspeptic symptoms referred by family physicians for open access upper endoscopy during 1997 and 2003 were analysed in relation to peptic ulcer disease, H. pylori infection and non-steroidal anti-inflammatory drug use. RESULTS: Among 2700 patients included, 405 (15%) had peptic ulcer disease and 14 (0.5%) had gastric cancer. There was a reduced trend from 1997 to 2003 in the prevalence of peptic ulcer disease (17, 20, 14, 16, 13, 14 and 14%, respectively, chi2 = 5.80, P = 0.016) (mainly because of decrease in duodenal ulcers), H. pylori infection (44, 50, 49, 44, 40, 40, 36 and 43%, respectively, chi2 = 13.55, P < 0.001) and non-steroidal anti-inflammatory drug use (13, 5, 5, 6, 3, 4, 4 and 5% respectively, chi2 = 13.61, P < 0.001). The prevalence of peptic ulcer disease, H. pylori infection and non-steroidal anti-inflammatory drug use between 2001 and 2003 were significantly lower than that between 1997 and 2000 (17% vs. 13%, OR = 0.78, 95% CI: 0.63-0.96, P = 0.020 for peptic ulcer disease; 47% vs. 39%, OR =0.72, 95% CI: 0.60-0.86, P < 0.001 for H. pylori infection; and 6% vs. 4%, OR = 0.56, 95% CI: 0.39-0.82, P = 0.002 for non-steroidal anti-inflammatory drug use). H. pylori infection was associated with both duodenal ulcer (OR = 15.87, 95% CI: 10.60-23.76, P < 0.001) and gastric ulcer (OR = 3.12, 95% CI: 2.15-4.53, P < 0.001) whereas non-steroidal anti-inflammatory drug use was only associated with gastric ulcer (OR = 2.97, 95% CI: 1.70-5.20, P < 0.001). CONCLUSIONS: The prevalence of peptic ulcer disease, mainly duodenal ulcers, was reduced in association with a decreasing trend in the prevalence of H. pylori infection and non-steroidal anti-inflammatory drug use from 1997 to 2003.

A pilot study of participation in faecal occult blood testing and screening colonoscopy after health education in Hong Kong.

Colorectal cancer is the second commonest cancer in Hong Kong. The screening behaviour of the Chinese population has not been assessed. The aim of this study is to report a pilot study of educating and subsequent evaluation of colorectal cancer screening behaviour in the Hong Kong Chinese population. Subjects were invited to attend a free health talk on colorectal cancer. Both self-paid faecal occult blood testing (FOBT) and free screening colonoscopy were offered after the education programme. Of the participants taking part in the education programme 113/119 (95%) completed the FOBT. Of the FOBT 8/113 (7%) showed positive result and three patients had neoplasia at colonoscopy. Twenty-five patients with negative FOBT also completed colonoscopy; two had adenomas. Screening colonoscopy after FOBT was accepted by 28% of subjects. Those younger than 65 years and those with a positive FOBT (7/8 versus 25/105 for those with negative FOBT, P=0.0003) were more likely to agree to screening colonoscopy. In conclusion, health education is important for ensuring high acceptance and implementation of colorectal cancer screening in Hong Kong Chinese. FOBT is an acceptable and feasible screening method in Hong Kong.

Coping strategies, illness perception, anxiety and depression of patients with idiopathic constipation: a population-based study.

BACKGROUND: Functional constipation has important psychological elements. AIM: To investigate the prevalence of functional constipation in an Asian population, and the interplay among functional constipation, anxiety/depression, perception and coping strategies. METHODS: An interview of 3282 patients was made by telephone survey. Constipation was diagnosed by Rome II criteria. Coping ability and anxiety/depression were assessed by validated questionnaires. RESULTS: Fourteen percent of the interviewees had constipation. Anxiety and depression scores were higher in constipated than in healthy subjects (P < 0.0001 and < 0.0001), and in female than male patients (P = 0.02 and < 0.0001). Patients who were aware of their symptoms perceived greater impact on their lives (P < 0.001). Frequent use of coping strategies associated with lower anxiety scores (P < 0.0001). Female were more frequently aware of the symptoms (P = 0.004), less frequently used coping strategies (P = 0.008). Regression analysis showed that female and high anxiety level were the independent factors for predicting the perception of constipation, whereas anxiety was the only independent factor for predicting the use of coping strategies. CONCLUSION: Constipation associated with anxiety and depression is prevalent in the general Asian population. Female sex and anxiety are important aetiological factors in constipation, affecting perception and the use of coping strategies.

Prevalence and characteristics of familial hepatocellular carcinoma caused by chronic hepatitis B infection in Hong Kong.

BACKGROUND: Hepatitis B virus infection is an important aetiological factor for hepatocellular carcinoma. Clusters of hepatocellular carcinoma have been observed in families infected with hepatitis B virus. AIM: To investigate the prevalence and characteristics of hepatocellular carcinoma associated with familial hepatitis B virus in Hong Kong. METHODS: Hepatitis B virus patients were screened for familial hepatocellular carcinoma using a standardized questionnaire. The clinical features of patients with familial hepatocellular carcinoma were compared with those of 118 patients with sporadic hepatocellular carcinoma attending the clinic during the same period. RESULTS: A total of 5080 patients were interviewed. Validation of the questionnaire indicated that the reliability was high. There were 22 families with familial hepatocellular carcinoma, giving a prevalence of 4.3 families/1000 hepatitis B virus carriers. The mean age of onset was 48.5 +/- 13 years in familial hepatocellular carcinoma and 62 +/- 11 years in sporadic hepatocellular carcinoma (P = 0.005). The ages of onset were 59 +/- 11, 40 +/- 10 and 18 +/- 4 years in the first, second and third generations, respectively (P < 0.0001), suggesting an anticipation phenomenon. Familial hepatocellular carcinoma patients were more likely to present with pain (70% vs. 10%, P < 0.0001), but not on routine screening (14% vs. 52%, P < 0.0001), than sporadic hepatocellular carcinoma patients. CONCLUSION: The prevalence of familial hepatocellular carcinoma is significant in Hong Kong. These patients show specific clinical features when compared with patients with sporadic hepatocellular carcinoma.

Different presentation of hepatitis B-related hepatocellular carcinoma in a cohort of 1863 young and old patients - implications for screening.

AIM: To compare the clinico-pathological features of hepatitis B virus-related hepatocellular carcinoma in young and old patients. METHODS: The clinico-pathological characteristics of hepatitis B virus-related hepatocellular carcinoma were compared in 1863 consecutive patients (121 patients, 40 years) seen at a single institution over the last 13 years. RESULTS: Young patients presented more often with pain (P < 0.0001), hepatomegaly (P = 0.01) and ruptured hepatocellular carcinoma (P = 0.02), whereas old patients presented with ankle oedema (P = 0.001), ascites (P = 0.002) and by routine screening (P = 0.035). Liver function, Child-Pugh grading and indocyanine green test were better preserved in young patients. They also had a higher alpha-foetoprotein concentration (P = 0.001), larger tumour size (P = 0.001) and more frequent metastasis (P = 0.008), but a similar surgical resection rate (33.6% vs. 28%), to old patients. There was no difference between the two groups in the overall post-resection survival rate, but there was a shorter survival in young patients with unresectable disease (3.6 months vs. 4.6 months, P = 0.004). Young patients with hepatocellular carcinoma often show a later presentation, but a higher resectability rate and similar survival rates, than old patients. The screening programme should include young hepatitis B virus carriers, even in the absence of cirrhosis.

Double-blind, randomized controlled study to assess the effects of lansoprazole 30 mg and lansoprazole 15 mg on 24-h oesophageal and intragastric pH in Chinese subjects with gastro-oesophageal reflux disease.

BACKGROUND: Previous studies have suggested that the acid secretory capacity of the Chinese population is lower than that of the Western population. AIM: To compare the effect of lansoprazole 30 mg and 15 mg once daily on the 24-h oesophageal and intragastric pH profiles in Chinese patients with gastro-oesophageal reflux disease. METHODS: Forty-four patients (male to female ratio, 27 : 17; mean age, 53 years; 55% with oesophagitis) with gastro-oesophageal reflux disease were randomized to receive lansoprazole 30 mg or 15 mg once daily for 4 weeks. Measurement of the 24-h oesophageal and intragastric pH, gastro-oesophageal reflux disease symptoms and quality of life was performed at baseline and during the last week of each dosing period. RESULTS: Lansoprazole 30 mg maintained an intragastric pH > 4 for 10.5 h vs. 9.6 h for lansoprazole 15 mg (P = 0.44). The percentage total time at oesophageal pH < 4 was similar for lansoprazole 30 mg and 15 mg (2.0% vs. 2.3%, P = 0.30). The proportion of patients with complete cure of heartburn and acid regurgitation and the quality of life assessment were similar for lansoprazole 30 mg and 15 mg. Both dosages of lansoprazole were well tolerated and the compliance was 100% in both groups. CONCLUSION: Lansoprazole dosages of 30 mg and 15 mg once daily provide a satisfactory decrease for oesophageal acid exposure and are equally effective for the treatment of gastro-oesophageal reflux disease in the Chinese population.

Long-term prospective follow-up of endoscopic oesophagitis in southern Chinese--prevalence and spectrum of the disease.

AIMS: To study the prevalence, clinical characteristics and long-term outcome of oesophagitis in Chinese patients. METHODS: Clinical and endoscopic data were collected prospectively from consecutive patients who underwent upper endoscopy between 1997 and 2001. Patients with endoscopic oesophagitis were graded according to the Los Angeles system and analysed according to their clinical presentation, endoscopic details, Helicobacter pylori status, non-steroidal anti-inflammatory drug history, co-morbidity and mortality. RESULTS: A total of 22,628 upper endoscopies were performed in 16,606 patients. Of these, 631 (3.8%) had endoscopic oesophagitis, 14 had benign oesophageal stricture (0.08%) and 10 had Barrett's oesophagus (0.06%). Most patients (94%) had either Los Angeles grade A or grade B oesophagitis. Patients who died during follow-up had a significantly higher incidence of co-morbid illness (100% vs. 63%, P < 0.001). By Cox regression analysis, the presence of gastrointestinal bleeding (P = 0.008), advanced age (P = 0.004) and the use of Ryle's tube (P = 0.043) were identified to be independent factors associated with mortality. CONCLUSIONS: Complicated gastro-oesophageal reflux disease is uncommon in the Asian population. Advanced age, use of Ryle's tube and the presence of gastrointestinal bleeding are associated with a poor long-term outcome, which is a reflection of the severe underlying co-morbidity.

A validated symptoms questionnaire (Chinese GERDQ) for the diagnosis of gastro-oesophageal reflux disease in the Chinese population.

BACKGROUND AND AIMS: To develop a validated gastro-oesophageal disease (GERD) symptom questionnaire for the Chinese population. METHODS: One hundred Chinese patients with GERD and 101 healthy Chinese controls were presented with a 20-item GERD questionnaire in the Chinese language (Chinese GERDQ). Quality of life in GERD patients was assessed by SF-36. A standard dose of proton pump inhibitors for 4 weeks was prescribed to 35 patients with newly diagnosed GERD. The Chinese GERDQ was performed before, 4 weeks and 8 weeks after treatment. Concept, content, construct, discriminant validity and reliability of the questionnaire were assessed. RESULTS: Seven items were selected by logistic regression to account for most of the differences between controls and GERD patients with a good reproducibility and internal consistency. A cut-off score of equal or greater than 12 was determined to discriminate between controls and GERD patients with a sensitivity of 82% and a specificity of 84%. The Chinese GERDQ correlated negatively with five domains of the SF-36 and discriminated between GERD patients who reported symptomatic improvement during proton pump inhibitor treatment and symptoms deterioration upon withdrawal of proton pump inhibitor treatment. CONCLUSIONS: The Chinese GERDQ could be used in epidemiological studies to assess the frequency and severity of GERD in patient populations and in interventional studies of GERD.

Effect of cyclo-oxygenase inhibitors on Helicobacter pylori susceptibility to metronidazole and clarithromycin.

BACKGROUND: We previously reported that aspirin inhibited Helicobacter pylori growth and suppressed the mutagenic effect of metronidazole. AIM: To determine the effects of a cyclo-oxygenase (COX)-2-specific inhibitor, SC-236, and a non-selective COX inhibitor, indometacin, on the growth, urease activity and antimicrobial susceptibility of H. pylori. METHODS: Three H. pylori reference strains, and 18 clinical isolates were treated with SC-236 or indometacin for 24 and 48 h. Growth, urease activity and susceptibility to clarithromycin and metronidazole of the bacteria were assessed by viable colony counting, spectrophotometry and E-test respectively. RESULTS: SC-236 and indometacin inhibited H. pylori growth in a dose-dependent manner with the lowest inhibitory concentrations of 0.03 and 0.1 mm, and the lethal concentrations of 0.09 and 0.3 mm, respectively. The numbers of CFU/mL in Brucella broth containing 0.09 mm SC-236 were 2 log lower at 24 h, and even 3 log lower at 48 h than that at 0 h (P = 0.035, compared with the vehicle control). Treatment of 0.3 mm indometacin reduced the number of CFU/mL by 1 log at 24 h compared with that at 0 h (P = 0.037 compared with the vehicle control). Helicobacter pylori urease activity began to decrease with 0.06 mm SC-236 at 24 h (P = 0.016), and 0.3 mm indometacin at 48 h (P = 0.025). MICs of metronidazole and clarithromycin against H. pylori were decreased significantly in the presence of 0.03 mm SC-236 or 0.1 mm indometacin (all P < 0.001). CONCLUSION: Both SC-236 and indometacin suppressed the growth and urease activity of H. pylori in a dose-dependent manner, and increased its susceptibility to the antibiotics.

Cholestatic jaundice caused by sequential carbimazole and propylthiouracil treatment for thyrotoxicosis.

A 36-year-old Chinese man presented to the Queen Mary Hospital in August 1999 with a 2-week history of jaundice due to propylthiouracil treatment for thyrotoxicosis. He had previously received carbimazole but had developed an urticarial skin rash after 2 weeks of treatment. The patient developed liver failure and fulminant pneumonitis shortly after hospital admission. Despite receiving treatment with broad-spectrum antibiotics and intravenous immunoglobulin, he died 11 days after the onset of the respiratory symptoms. Postmortem examination using electron microscopy showed typical glycogen bodies within the cytoplasm of the hepatocytes, which corresponded to eosinophilic cytoplasmic inclusion bodies visible under light microscopy. Immunohistochemical studies of the inclusion bodies were positive for carcinoembryonic antigen and albumin, and negative for fibrinogen, complement protein C3, immunoglobulins G, M, and A, alpha-fetoprotein, and alpha-1-antitrypsin. This is the first report of a patient who received two sequential antithyroid drugs and developed predominate cholestasis with unique histological features. Extreme caution should be taken when a patient develops allergy to one type of antithyroid drug, because cross-reactivity may develop to the other type.

Normal 24-hour ambulatory proximal and distal gastroesophageal reflux parameters in Chinese.

OBJECTIVE: To quantify normal proximal and distal oesophageal acid parameters in healthy Chinese. DESIGN: Observational study. SETTING: University teaching hospital, Hong Kong. SUBJECTS AND METHODS: Twenty healthy adults who were not on medication and were free from gastrointestinal symptoms were recruited by advertisement. Ambulatory oesophageal acid (pH<4) exposure parameters were recorded at distal and proximal sites, 5 and 20 cm, respectively above the lower oesophageal sphincter. RESULTS: The 95th percentile for reflux parameters assessed in the distal/proximal oesophagus were: percent total time pH<4, 4.6/0.7%; percent upright time pH<4, 7.0/1.1%; percent supine time pH<4, 4.5/0.5%; number of reflux episodes, 73/12; number of reflux episodes with pH<4 for >5 minutes, 4/0; and the longest single acid exposure episode, 11.2/3.0 minutes. CONCLUSION: Physiological gastroesophageal reflux occurs in healthy Chinese. These initial data provide a preliminary reference range that could be utilised by laboratories studying Chinese subjects.