Feng-Woei Tsay

A new look at anti-Helicobacter pylori therapy.

With the rising prevalence of antimicrobial resistance, the treatment success of standard triple therapy has recently declined to unacceptable levels (i.e., 80% or less) in most countries. Therefore, several treatment regimens have emerged to cure Helicobacter pylori (H. pylori) infection. Novel first-line anti-H. pylori therapies in 2011 include sequential therapy, concomitant quadruple therapy, hybrid (dual-concomitant) therapy and bismuth-containing quadruple therapy. After the failure of standard triple therapy, a bismuth-containing quadruple therapy comprising a proton pump inhibitor (PPI), bismuth, tetracycline and metronidazole can be employed as rescue treatment. Recently, triple therapy combining a PPI, levofloxacin and amoxicillin has been proposed as an alternative to the standard rescue therapy. This salvage regimen can achieve a higher eradication rate than bismuth-containing quadruple therapy in some regions and has less adverse effects. The best second-line therapy for patients who fail to eradicate H. pylori with first-line therapies containing clarithromycin, amoxicillin and metronidazole is unclear. However, a levofloxacin-based triple therapy is an accepted rescue treatment. Most guidelines suggest that patients requiring third-line therapy should be referred to a medical center and treated according to the antibiotic susceptibility test. Nonetheless, an empirical therapy (such as levofloxacin-based or furazolidone-based therapies) can be employed to terminate H. pylori infection if antimicrobial sensitivity data are unavailable.

Helicobacter pylori infection and the risk of gastric malignancy.

OBJECTIVE:This prospective cohort study investigated the impact of Helicobacter pylori infection on the development of various gastric malignancies.METHODS:We prospectively followed up 1,225 dyspeptic Taiwanese who had nonulcer dyspepsia, gastric ulcers, or duodenal ulcers at enrollment. Among them, 618 (50.4%) had H. pylori infection and 607 (49.6%) did not. Patients underwent endoscopy at enrollment and at 1- to 3-yr intervals thereafter.RESULTS:During a mean follow-up of 6.3 yr, gastric adenocarcinoma developed in 7 of the 618 H. pylori-infected patients, but in none of the 607 uninfected patients (1.1% vs 0.0%, P = 0.015). The incidence of gastric lymphoma was 0.2% (1/618) and 0% in H. pylori-infected and uninfected patients. Taken together, the development rate of gastric malignancy in H. pylori-infected patients was significantly higher than that in uninfected patients (1.3% vs 0%, P = 0.007). Among H. pylori-infected subjects, the incidence of gastric malignancy was similar between those receiving and not receiving eradication therapy (1.4% vs 1.2%). Multivariate analysis showed that intestinal metaplasia was the only independent factor predicting subsequent development of gastric malignancy in H. pylori-infected subjects with an odds ratio of 4.5 (95% CI 1.1–19.1).CONCLUSIONS:In this prospective cohort study, all gastric malignancies, including adenocarcinoma and lymphoma, developed in H. pylori-infected patients. The finding implies that H. pylori is a necessary cause of most gastric malignancies. Follow-up for H. pylori-infected patients who have intestinal metaplasia is indicated.

A Prospective Randomized Trial of Esomeprazole- versus Pantoprazole-Based Triple Therapy for Helicobacter pylori Eradication

OBJECTIVE:This prospective, randomized, controlled, head-to-head study was conducted to compare the efficacies of esomeprazole- and pantoprazole-based triple therapies for Helicobacter pylori eradication.METHODS:From January 2002 to October 2003, 200 H. pylori-infected patients were randomly assigned to undergo twice daily treatment with esomeprazole 40 mg (n = 100) or pantoprazole 40 mg (n = 100) combined with clarithromycin 500 mg and amoxicillin 1 g for 1 wk (ECA and PCA groups, respectively). Follow-up endoscopy was performed at 8 wks after the end of treatment to assess the treatment response.RESULTS:Intention-to-treat analysis demonstrated a significantly higher eradication rate for the ECA group than for the PCA group (94% vs 82%, respectively, p = 0.009). Per-protocol analysis also showed similar results (97% vs 84%, p = 0.003). Both groups had similar frequencies of adverse events (15% vs 24%) and drug compliance (97% vs 96%). Multivariate analysis disclosed that the use of esomeprazole (OR: 1.56, 95% CI, 1.11–2.19) and good compliance 7.39 (95% CI, 1.27–42.95) were independent predictors of treatment success. Alcohol drinking was an independent predictor of eradication failure (OR: 0.18; 95% CI, 0.06–0.54).CONCLUSION:Esomeprazole-based triple therapy demonstrated a higher eradication rate than pantoprazole-based regimen. The differences in eradiation efficacies between the two study groups may be related to the more powerful acid inhibition effect and stronger anti-H. pylori activity of esomeprazole compared to pantoprazole.

Endoscopic papillary large balloon dilation alone without sphincterotomy for the treatment of large common bile duct stones

BackgroundLethal pancreatitis has been reported after treatment for common bile duct stones using small endoscopic papillary balloon dilation.MethodsWe retrospectively evaluated the safety and efficacy of using large balloon dilation alone without the use of sphincterotomy for the treatment of large common bile duct stones in Kaohsiung Veterans General Hospital. Success rate of stone clearance, procedure-related adverse events and incidents, frequency of mechanical lithotripsy use, and recurrent stones were recorded.ResultsA total of 247 patients were reviewed in the current study. The mean age of the patients was 71.2 years. Most of them had comorbidities. Mean stone size was 16.4 mm. Among the patients, 132 (53.4%) had an intact gallbladder and 121 (49%) had a juxtapapillary diverticulum. The mean size of dilating balloon used was 13.2 mm. The mean duration of the dilating procedure was 4.7 min. There were 39 (15.8%) patients required the help of mechanical lithotripsy while retrieving the stones. The final success rate of complete retrieval of stones was 92.7%. The rate of pancreatic duct enhancement was 26.7% (66/247). There were 3 (1.2%) adverse events and 6 (2.4%) intra-procedure bleeding incidents. All patients recovered completely after conservative and endoscopic treatment respectively, and no procedure-related mortality was noted. 172 patients had a follow-up duration of more than 6 months and among these, 25 patients had recurrent common bile duct stones. It was significantly correlated to the common bile duct size (p = 0.036)ConclusionsEndoscopic papillary large balloon dilation alone is simple, safe, and effective in dealing with large common bile duct stones in relatively aged and debilitated patients.

Randomized Controlled Trial Comparing 7-Day Triple, 10-Day Sequential, and 7-Day Concomitant Therapies for Helicobacter pylori Infection

ABSTRACT With the rising prevalence of antimicrobial resistance, the failure rate of the standard triple therapy for Helicobacter pylori infection is increasing. Sequential therapy and concomitant therapy have been recommended to replace standard triple therapy for H. pylori eradication in regions with high clarithromycin resistance. The aim of this prospective, randomized, and controlled study was to simultaneously assess the efficacies of 10-day sequential and 7-day concomitant therapies versus a 7-day standard triple therapy for treating H. pylori infection. Consecutive H. pylori-infected subjects were randomly assigned to a 7-day standard triple therapy (pantoprazole, clarithromycin, and amoxicillin for 7 days), a 10-day sequential therapy (pantoprazole and amoxicillin for 5 days, followed by pantoprazole, clarithromycin, and metronidazole for a further 5 days), or a 7-day quadruple therapy (pantoprazole, clarithromycin, amoxicillin, and metronidazole for 7 days). H. pylori status was confirmed 6 weeks after therapy. Three hundred seven H. pylori-infected participants were randomized to receive triple (n = 103), sequential (n = 102), or concomitant (n = 102) therapies. The eradication rates by an intention-to-treat analysis in the three treatment groups were 81.6% (95% confidence interval [CI], 74.1% to 89.0%), 89.2% (95% CI, 83.2% to 95.2%), and 94.1% (95% CI, 89.5% to 98.7%). The seven-day concomitant therapy had a higher eradication rate than did the 7-day triple therapy (difference, 12.5%; 95% CI, 3.7% to 21.3%). There were no significant differences in the eradication rates between the sequential and standard triple therapies. All three treatments exhibited similar frequencies of adverse events (8.7%, 8.8%, and 13.7%, respectively) and drug compliance (99.0%, 98.0%, and 100.0%, respectively). In conclusion, the seven-day concomitant therapy is superior to the 7-day standard triple therapy for H. pylori eradication. Additionally, it is less complex than the 10-day sequential therapy because the drugs are not changed halfway through the treatment course. (This study has been registered at ClinicalTrials.gov under registration no. NCT1769365.)

Low-dose terlipressin plus banding ligation versus low-dose terlipressin alone in the prevention of very early rebleeding of oesophageal varices.

Background: Very early rebleeding is frequently encountered in patients with acute oesophageal variceal bleeding. A trial was designed to assess the efficacy and safety in patients with no active bleeding at endoscopy, receiving banding ligation association with terlipressin to prevent very early rebleeding. Methods: Patients with no active variceal bleeding at endoscopy were evaluated. Eligible patients were randomised to receive terlipressin infusion alone for 5 days (Terlipressin group) or banding ligation plus terlipressin infusion for 2 days (Combined group). Primary endpoints were treatment failure and very early rebleeding. Results: The terlipressin group was composed of 46 patients and the Combined group was composed of 47 patients. Both groups were comparable in terms of baseline data. Forty-eight-hour haemostasis was achieved in 91% in the Terlipressin group and 98% in the Combined group (p = 0.20). Very early rebleeding within 48–120 h occurred in 7 patients (15%) in the Terlipressin group but not in any patients (0%) in the Combined group (p = 0.006). Treatment failure was 24% in the Terlipressin group and 2% in the Combined group (p = 0.002). Multivariate analysis revealed that treatment (OR 0.081; 95% CI 0.010 to 0.627) was the only predictive factor of very early rebleeding. Blood requirement was significantly lower in the Combined group than in the Terlipressin group. Complications and 6-week survival were similar in both groups. Conclusions: Combination of banding ligation and terlipressin infusion for 2 days was superior to only infusion of terlipressin for 5 days in the reduction of very early rebleeding and treatment failure in patients with inactive variceal bleeding at endoscopy. Trial registration number: ISRCTN28353453

Helicobacter pylori infection: a randomized, controlled study comparing 2 rescue therapies after failure of standard triple therapies.

Antibiotic resistance to amoxicillin in second-line eradication therapy for Helicobacter pylori infection is much less frequent than resistance to metronidazole. We conducted a randomized, controlled study to compare the efficacies of standard quadruple rescue therapy and a new therapy with amoxicillin replacing metronidazole for patients failing first-line eradication treatment. We randomly assigned 120 patients who failed H. pylori eradication using a proton pump inhibitor plus clarithromycin and amoxicillin to undergo a 1-week rescue therapy with esomeprazole, bismuth subcitrate, and tetracycline plus either metronidazole (EBTM group, n = 62) or amoxicillin (EBTA group, n = 58). We used follow-up endoscopy 8 weeks after the end of treatment to assess the treatment response. We also examined and analyzed antibiotic resistances and CYP2C19 genotypes.Intention-to-treat analysis demonstrated that the EBTA group had a significantly lower eradication rate than the EBTM group (62% vs. 81%, respectively, p = 0.02). Per-protocol analysis showed similar results (64% vs. 83%, p = 0.01). However, the EBTA group had less frequency of adverse events than the EBTM group (19% vs. 44%, p < 0.01). Both groups had good drug compliance (both 97%). Antibiotic susceptibility tests showed that the frequency of amoxicillin-resistant strains was much less than that of metronidazole-resistant strains (0% vs. 54%, respectively), and there were no significant differences between H. pylori eradication rates and antibiotic resistances.In conclusion, EBTA quadruple therapy demonstrated a lower eradication rate than standard EBTM therapy in second-line rescue treatment. The discrepancy between in vitro antibiotic susceptibility and in vivo eradication response is probably due to drug interactions between combined antibiotics or some unknown causes, and should not be neglected in H. pylori therapy.Abbreviations: b.d. = twice a day, CI = confidence interval, EBTA = esomeprazole, bismuth subcitrate, tetracycline plus amoxicillin, EBTM = esomeprazole, bismuth subcitrate, tetracycline plus metronidazole, hetEM = heterogeneous extensive metabolizer, homEM = homogeneous extensive metabolizer, ITT = intention-to-treat, PM = poor metabolizer, PP = per-protocol, PPI = proton pump inhibitor, q.d.s. = 4 times a day.

Ten‐Day Quadruple Therapy Comprising Proton‐Pump Inhibitor, Bismuth, Tetracycline, and Levofloxacin Achieves a High Eradication Rate for Helicobacter pylori Infection after Failure of Sequential Therapy

Sequential therapy has been recommended in the Maastricht IV/Florence Consensus Report as the first‐line treatment for Helicobacter pylori eradication in regions with high clarithromycin resistance. However, it fails in 5–24% of infected subjects, and the recommended levofloxacin‐containing triple rescue therapy only achieves a 77% eradication rate after failure of sequential therapy.

Sequential therapy achieves a higher eradication rate than standard triple therapy in Taiwan

Background and Aims:  Most clinical trials concerning sequential therapy have been conducted in Italy. The efficacy of sequential therapy for Helicobacter pylori (H. pylori) eradication in Asia remains unclear. The aim of this study was to compare the efficacy of sequential therapy with standard triple therapy in Taiwan.

The compliance of doctors with viral hepatitis B screening and antiviral prophylaxis in cancer patients receiving cytotoxic chemotherapy using a hospital-based screening reminder system.

Background and Aim Screenings for hepatitis B surface antigen (HBsAg) and antiviral prophylaxis are recommended for HBsAg-positive patients before the start of cytotoxic chemotherapy; however, compliance with these recommendations varies among doctors. We investigated the compliance of doctors with these recommendations using a reminder system and assessed the outcomes of HBsAg-positive patients receiving cytotoxic chemotherapy. Methods Using a computer-assisted reminder system, doctors were alerted of both HBsAg screening and antiviral prophylaxis prior to prescribing chemotherapy. The compliance between different doctors and outcomes of patients were investigated during the period of execution of this system. The rates of compliance with both recommendations were compared among various cancer types. Results A total of 1053 patients were enrolled, of which only 88 had previous data pertaining to HBsAg status. Using this reminder system, an overall screening rate of 85.5% (825/965) was achieved and did not significantly differ according to cancer type. However, the overall antiviral prophylactic rate was only 45.5% (61/134). The rates of antiviral prophylaxis were lower for doctors treating lung, breast and colorectal cancers than for those treating hematological malignancies (all p<0.05). Consequently, the rate of HBV reactivation was lower in patients who received antiviral prophylaxis than in those who did not (1.6% vs. 15.1%; p<0.01). Multivariate analysis revealed that male gender and antiviral prophylaxis were both related to reactivation of hepatitis B (p<0.05). Conclusions By using this reminder system, the overall screening rate for HBsAg was satisfactory, whereas the antiviral prophylaxis was inadequate in patients with solid tumors due to the varying compliance of the attending doctors. Further strategies to improve both screening and prophylaxis are needed to minimize HBV-related events during cytotoxic chemotherapy.