Ping-Huei Tseng

Sequential versus triple therapy for the first-line treatment of Helicobacter pylori: a multicentre, open-label, randomised trial

BACKGROUND Whether sequential treatment can replace triple therapy as the standard treatment for Helicobacter pylori infection is unknown. We compared the efficacy of sequential treatment for 10 days and 14 days with triple therapy for 14 days in first-line treatment. METHODS For this multicentre, open-label, randomised trial, we recruited patients (≥20 years of age) with H pylori infection from six centres in Taiwan. Using a computer-generated randomisation sequence, we randomly allocated patients (1:1:1; block sizes of six) to either sequential treatment (lansoprazole 30 mg and amoxicillin 1 g for the first 7 days, followed by lansoprazole 30 mg, clarithromycin 500 mg, and metronidazole 500 mg for another 7 days; with all drugs given twice daily) for either 10 days (S-10) or 14 days (S-14), of 14 days of triple therapy (T-14; lansoprazole 30 mg, amoxicillin 1 g, and clarithromycin 500 mg for 14 days; with all drugs given twice daily). Investigators were masked to treatment allocation. Our primary outcome was the eradication rate in first-line treatment by intention-to-treat (ITT) and per-protocol (PP) analyses. This trial is registered with ClinicalTrials.gov, number NCT01042184. FINDINGS Between Dec 28, 2009, and Sept 24, 2011, we enrolled 900 patients: 300 to each group. The eradication rate was 90·7% (95% CI 87·4-94·0; 272 of 300 patients) in the S-14 group, 87·0% (83·2-90·8; 261 of 300 patients) in the S-10 group, and 82·3% (78·0-86·6; 247 of 300 patients) in the T-14 group. Treatment efficacy was better in the S-14 group than it was in the T-14 group in both the ITT analysis (number needed to treat of 12·0 [95% CI 7·2-34·5]; p=0·003) and PP analyses (13·7 [8·3-40], p=0·003). We recorded no significant difference in the occurrence of adverse effects or in compliance between the three groups. INTERPRETATION Our findings lend support to the use of sequential treatment as the standard first-line treatment for H pylori infection. FUNDING National Taiwan University Hospital and National Science Council.

Narrow-band imaging with magnifying endoscopy for the screening of esophageal cancer in patients with primary head and neck cancers.

BACKGROUND AND STUDY AIM Although narrow-band imaging (NBI) in endoscopy can improve detection of early-stage esophageal malignancies in patients with head and neck cancers, false-positive results may be obtained in areas with nonspecific inflammatory changes. This study evaluated the feasibility of primary screening with NBI and magnification for the presence of esophageal malignancies in these cancer patients. PATIENTS AND METHODS Sixty-nine patients with documented head and neck cancers were enrolled from April 2008 to January 2009. All patients underwent a meticulous endoscopic examination of the esophagus using a conventional white-light system followed by re-examination using the NBI system and final confirmation with NBI plus magnification. RESULTS Twenty-one patients (30.4 %) were confirmed to have esophageal neoplasia. Among these 21, 16 (76.2 %) had synchronous lesions, 9 (42.9 %) were asymptomatic, and 10 (47.6 %) had early-stage neoplasia. The incidence of multiple esophageal neoplasia was 57.1 %. NBI was more effective than conventional endoscopy in detecting neoplastic lesions (35 lesions in 21 patients vs. 22 lesions in 18 patients) and was particularly effective in patients with dysplasia (13 lesions in 9 patients vs. 3 lesions in 3 patients). The sensitivity and accuracy of detection were 62.9 % and 64.4 % for conventional endoscopy, 100 % and 86.7 % for NBI alone, and 100 % and 95.6 % for NBI with high magnification, respectively. CONCLUSIONS Compared with current approaches, NBI followed by high magnification significantly increases the accuracy of detection of esophageal neoplasia in patients with head and neck cancers. The result warrants conducting prospective randomized controlled study to confirm its efficacy.

Prevalence and clinical characteristics of Barrett's esophagus in a Chinese general population.

Background The prevalence of Barrett esophagus (BE) remains elusive in the general populations. Goals The purpose of this study was to identify the prevalence and clinical characteristics of BE in a Chinese general population. Study Between June 2003 and December 2006, consecutive subjects were evaluated via upper gastrointestinal endoscopy during a routine health examination. Patients were evaluated for any abnormalities, including endoscopically suspected esophageal metaplasia (ESEM) and erosive esophagitis (EE). Biopsies were attained from patients with ESEM to confirm a diagnosis of BE. The demographic data and endoscopic findings were retrospectively analyzed. Results Of the 19,812 endoscopies performed, 56 patients (0.28%) were diagnosed with ESEM and 3129 patients (15.7%) with EE. Twelve of the 56 patients diagnosed with ESEM (0.06% of the total number of patients who underwent endoscopy) were confirmed to have BE after histologic analysis of the biopsies. Patients with BE were older than patients without BE (61.6 vs. 51.7 y), and only one of the 12 patients diagnosed with BE (8.3%) reported typical gastroesophageal reflux symptoms. A majority of the BE patients were categorized as short-segment BE (91.7%) and concomitant EE was found in 4 (33.3%). Smoking, alcohol, and metabolic disorders seemed to be associated with the presence of BE and EE. Conclusions The prevalence of BE in a Chinese general population was lower than that in other reported studies, particularly in comparison with the studies originating from Western countries. Patients with advanced age and metabolic disorders are risk factors for developing BE.

Association Between Early Stage Colon Neoplasms and False-negative Results From the Fecal Immunochemical Test

BACKGROUND & AIMS The fecal immunochemical test (FIT) can identify patients with advanced colorectal neoplasms, but it also has a high rate of false-negative results. It would be helpful to characterize colorectal neoplasms that are not detected by FIT to aid in development of new tests. We characterized colorectal neoplasms from patients who had negative results from the FIT. METHODS We analyzed data from 18,296 subjects who were screened for colorectal cancer by colonoscopy and the FIT at the Health Management Center of National Taiwan University Hospital from September 2005 through September 2010. We identified 4045 subjects with colorectal neoplasms (3385 with nonadvanced adenomas, 632 with advanced adenomas, and 28 with cancer). We analyzed the sensitivity of the FIT in identifying these patients, along with information on lesion size, location, and morphology. RESULTS The FIT identified patients with nonadvanced adenomas, advanced adenomas, and cancer with sensitivity values of 10.6% (95% confidence interval [CI], 10.2%-12.3%), 28.0% (95% CI, 24.6%-31.7%), and 78.6% (95% CI, 58.5%-91.0%), respectively. The FIT detected proximal advanced adenomas and nonpolypoid lesions with lower levels of sensitivity than distal advanced adenomas; it had a high false-negative rate in detection of adenomas <15 mm (adjusted odds ratio, 2.85; 95% CI, 1.79-4.54) and nonpolypoid adenomas (adjusted odds ratio, 2.15; 95% CI, 1.22-3.80), after adjusting for demographic characteristics, colonoscopy findings, and potential confounders. The FIT produced a higher percentage of false-negative results in detection of carcinoma in situ and T1 cancer than in T2-T4 cancers (66.7% sensitivity vs 100%; P = .049). CONCLUSIONS The FIT produces a high rate of false-negative results for patients with small or nonpolypoid adenomas. Early-stage cancers are associated with a high rate of false-negative results from the FIT.

Efficacy of genotypic resistance-guided sequential therapy in the third-line treatment of refractory Helicobacter pylori infection: a multicentre clinical trial

OBJECTIVES The efficacy of sequential therapy and the applicability of genotypic resistance to guide the selection of antibiotics in the third-line treatment of Helicobacter pylori have not been reported. We aimed to assess the efficacy of genotypic resistance-guided sequential therapy in third-line treatment. METHODS Genotypic and phenotypic resistances were determined in patients who failed at least two eradication therapies by PCR with direct sequencing and agar dilution test, respectively. The patients were retreated with sequential therapy containing esomeprazole and amoxicillin for the first 7 days, followed by esomeprazole and metronidazole plus clarithromycin, levofloxacin or tetracycline for another 7 days (all twice daily), according to genotypic resistance determined using gastric biopsy specimens. Eradication status was determined by the (13)C-urea breath test. Trial registered at clinicaltrials.gov (identifier: NCT01032655). RESULTS The overall eradication rate was 80.7% (109/135, 95% CI 73.3%-86.5%) in the intention-to-treat analysis. The presence of amoxicillin resistance (OR 6.83, 95% CI 1.62-28.86, P = 0.009) and prior sequential therapy (OR 4.77, 95% CI 1.315-17.3, P = 0.017), but not tetracycline resistance (tetracycline group), were associated with treatment failure. The eradication rates in patients who received clarithromycin-, levofloxacin- and tetracycline-based sequential therapies were 78.9% (15/19), 92.2% (47/51) and 71.4% (25/35) in strains susceptible to clarithromycin, levofloxacin and tetracycline, respectively. CONCLUSIONS A simple molecular method guiding sequential therapy can achieve a high eradication rate in the third-line treatment of refractory H. pylori infection.

Distinct aetiopathogenesis in subgroups of functional dyspepsia according to the Rome III criteria

Background and objective Whether there is distinct pathogenesis in subgroups of functional dyspepsia (FD), the postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS) remains controversial. We aimed to identify the risk factors of FD and its subgroups in the Chinese population. Methods Patients with dyspepsia and healthy subjects who underwent gastric cancer screening were enrolled in this multicentre study from 2010 to 2012. All patients were evaluated by questionnaire, oesophagoduodenoscopy, histological examination and Helicobacter pylori tests. Subgroups of FD were classified according to the Rome III criteria. Psychiatric stress was assessed by the short form Brief Symptom Rating Scale. CagA and VacA genotypes were determined by PCR. Results Of 2378 patients screened for eligibility, 771 and 491 fulfilled the diagnostic criteria of uninvestigated dyspepsia and FD, respectively. 298 (60.7%) and 353 (71.9%) individuals were diagnosed with EPS and PDS, respectively, whereas 169 (34.4%) had the overlap syndrome. As compared with 1031 healthy controls, PDS and EPS shared some common risk factors, including younger age (OR 0.95; 99.5% CI 0.93 to 0.98), non-steroidal anti-inflammatory drugs (OR 6.60; 99.5% CI 3.13 to 13.90), anxiety (OR 3.41; 99.5% CI 2.01 to 5.77) and concomitant IBS (OR 6.89; 99.5% CI 3.41 to 13.94). By contrast, H. pylori (OR 1.86; 99.5% CI 1.01 to 3.45), unmarried status (OR 4.22; 99.5% CI 2.02 to 8.81), sleep disturbance (OR 2.56; 99.5% CI 1.29 to 5.07) and depression (OR 2.34; 99.5% CI 1.04 to 5.36) were associated with PDS. Moderate to severe antral atrophy and CagA positive strains were also more prevalent in PDS. Conclusions Different risk factors exist among FD subgroups based on the Rome III criteria, indicating distinct aetiopathogenesis of the subdivisions that may necessitate different therapeutic strategies.

Randomised clinical trial: high‐dose vs. standard‐dose proton pump inhibitors for the prevention of recurrent haemorrhage after combined endoscopic haemostasis of bleeding peptic ulcers

The optimal dosage of intravenous proton pump inhibitors (PPIs) for the prevention of peptic ulcer rebleeding remains unclear.

Use of transnasal endoscopy for screening of esophageal squamous cell carcinoma in high-risk patients: Yield rate, completion rate, and safety

Patients with head and neck squamous cell carcinoma are at high risk for synchronous and/or metachronous esophageal cancer. The present study aimed to evaluate the feasibility and safety of unsedated transnasal endoscopy (TNE) for screening these high‐risk patients.

Association of Diabetes and HbA1c Levels With Gastrointestinal Manifestations

OBJECTIVE To determine the prevalence of gastrointestinal (GI) manifestations associated with diabetes mellitus (DM) in a Taiwanese population undergoing bidirectional endoscopies. RESEARCH DESIGN AND METHODS Subjects voluntarily undergoing upper endoscopy/colonoscopy as part of a medical examination at the National Taiwan University Hospital were recruited during 2009. Diagnosis of DM included past history of DM, fasting plasma glucose ≥126 mg/dL, or glycated hemoglobin (HbA1c) ≥6.5%. Comparisons were made between diabetic and nondiabetic subjects, subjects with lower and higher HbA1c levels, and diabetic subjects with and without complications, respectively, for their GI symptoms, noninvasive GI testing results, and endoscopic findings. RESULTS Among 7,770 study subjects, 722 (9.3%) were diagnosed with DM. The overall prevalence of GI symptoms was lower in DM subjects (30.3 vs. 35.4%, P = 0.006). In contrast, the prevalence of erosive esophagitis (34.3 vs. 28.6%, P = 0.002), Barretts esophagus (0.6 vs. 0.1%, P = 0.001), peptic ulcer disease (14.8 vs. 8.5%, P < 0.001), gastric neoplasms (1.8 vs. 0.7%, P = 0.003), and colonic neoplasms (26.6 vs. 16.5%, P < 0.001) was higher in diabetic subjects. Diagnostic accuracy of immunochemical fecal occult blood test for colonic neoplasms was significantly decreased in DM (70.7 vs. 81.7%, P < 0.001). Higher HbA1c levels were associated with a decrease of GI symptoms and an increase of endoscopic abnormalities. Diabetic subjects with complications had a higher prevalence of colonic neoplasms (39.2 vs. 24.5%, P = 0.002) than those without. CONCLUSIONS DM and higher levels of HbA1c were associated with lower prevalence of GI symptoms but higher prevalence of endoscopic abnormalities.

Performance of Narrow Band Imaging and Magnification Endoscopy in the Prediction of Therapeutic Response in Patients With Gastroesophageal Reflux Disease

Background Imaging-enhanced endoscopy enhances the contrast of the mucosal surface and helps in the diagnosis of gastroesophageal reflux disease. However, whether the increased detection of subtle erosive foci corresponds to the effect of acid suppression remains elusive. Goals We aim to evaluate the utility of narrow band imaging with and without magnification endoscopy in the prediction of therapeutic response in patients with reflux. Study Endoscopic evaluation with conventional white light, narrow band imaging, and narrow band imaging with magnification was performed sequentially in consecutive patients with reflux. All patients received proton pump inhibitor for 14 days. Their therapeutic responses were correlated with the baseline endoscopic findings, including mucosal breaks under standard endoscopy, mucosal brownish changes under narrow band imaging, and increased and/or dilated intrapapillary capillary loops or microerosions under narrow band imaging with magnification. Results Of a total of 82 patients, 22 (26.8%) patients were diagnosed with erosive disease under standard endoscopy. Among the remaining 60 (73.2%) patients, 14 (23.3%) and 30 (50%) were considered erosive under narrow band imaging and narrow band imaging with magnification, respectively. Sixty-five (79.3%) patients showed a positive therapeutic response. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in predicting therapeutic response were 33.8%, 100%, 100%, 28.3%, and 47.6%, respectively, for standard endoscopy; 52.3%, 88.2%, 94.4%, 32.6%, and 59.8%, respectively, for narrow band imaging; and 70.8%, 64.7%, 88.4%, 36.6%, and 69.5%, respectively, for narrow band imaging with magnification. Conclusions Narrow band imaging with and without magnification endoscopy substantially improve our ability to predict therapeutic response in patients with gastroesophageal reflux.