Clinical outcome and influencing factors of a new short-term quadruple therapy for Helicobacter pylori eradication: a randomized controlled trial (MACLOR study).

BACKGROUND: Short-term therapies for eradicating Helicobacter pylori in selected patients might offer advantages in terms of costs, compliance, and adverse effects in contrast to standard 1-week triple therapy. METHODS: To determine eradication success and influencing factors in a new short-term quadruple therapy, a total of 243 patients positive for H pylori were randomly assigned to 1 of 3 regimens according to age, smoking status, and diagnosis: a 5-day treatment with 3 antibiotics (amoxicillin, 1 g twice daily [bid]; clarithromycin, 250 mg bid; and metronidazole, 400 mg bid) and lansoprazole (30 mg bid [L5; reference treatment]) or ranitidine hydrochloride (300 mg bid [R5]), or the same 3-day antibiotic-lansoprazole combination (L3) with a 2-day pretreatment with lansoprazole. RESULTS: A total of 234 patients completed the study. On an intention-to-treat basis, overall eradication of H pylori was confirmed in 86.4%: 89.2% in the L5 group vs 81.2% in the L3 group vs 88.8% in the R5 group; differences were not significant. Multiple logistic regression analysis showed that younger age (<55 years; P =.03), history of peptic ulcer disease (P =.04), smoking (P =.03), metronidazole resistance (P =.003), low ranitidine trough serum concentrations (P =.005), cytotoxin-associated gene A-negative strains in peptic ulcer disease (P =.04), and outer inflammatory protein A-positive strains (P =.02) were associated with eradication failure. CONCLUSIONS: This new quadruple H pylori eradication regimen is efficacious, safe, well tolerated, and cost saving, and may be a treatment option for patients older than 55 years with no history of peptic ulcer disease. Furthermore, strains that are sensitive to all antibiotics, cytotoxin-associated gene A-positive, and outer inflammatory protein A-negative could be suitable for short-term quadruple therapy. Patients with an unfavorable combination of characteristics should be treated for a minimum of 7 days.

Development of dominant bile duct stenoses in patients with primary sclerosing cholangitis treated with ursodeoxycholic acid: outcome after endoscopic treatment.

BACKGROUND/AIMS: Primary sclerosing cholangitis is characterized by progressive fibrotic inflammation and obliteration of intra- and/or extrahepatic bile ducts. METHODS: In a prospective study of 106 patients treated for up to 13 years with ursodeoxycholic acid, the development of major bile duct stenoses and the efficacy of endoscopic measures have been evaluated. RESULTS: Of 106 patients ten had major duct stenoses at entry, and during a median follow-up period of 5.0 years another 43 developed a dominant stenosis. Fifty-two patients with dominant stenoses were treated endoscopically by repeated balloon dilatations and five patients were temporarily stented. Complications of endoscopic procedures were pancreatitis (5.2%), bacterial cholangitis (3.3%) and bile duct perforation (0.5%). Five years after the first dilatation of a dominant stenosis the Kaplan-Meier survival rates free of liver transplantation were 100% in stage 2, 72% in stage 3 and 50% in stage 4 disease. The actuarial survival free of liver transplantation of the whole group at 3, 5 and 7 years were 0.987, 0.935 and 0.891 and the corresponding survival rates predicted with the Mayo multicenter survival model were 0.860, 0.775 and 0.737 (P<0.001). CONCLUSIONS: In advanced disease, occlusion of major bile ducts with time occurs in the majority of patients. Endoscopic opening of dominant stenoses is effective and appears to be a valuable addition to the medical treatment of such patients.

Telomerase activity in chronic inflammatory bowel disease.

Patients with ulcerative colitis have an increased risk of developing colorectal cancer. Telomerase appears to be associated with cellular immortality and might serve as a diagnostic and prognostic marker in carcinogenesis. To test this hypothesis we measured telomerase by a score from 0 (no activity) to 4 (very high activity) in specimens obtained surgically from seven patients with adenocarcinoma of the colon. Intraindividual comparison was made among normal tissue (mean score +/- SD: 0.7 +/- 1.0), tissues adjacent to the tumor (2.7 +/- 0.8), and the tumor center (3.0 +/- 1.0). In addition, from 18 patients with ulcerative colitis, 10 patients with Crohn's disease, and 14 patients without chronic inflammatory bowel disease, biopsies were collected from normal and inflamed areas of the colon. Independent of the duration (0-32 years), grade, and location of the diseases, the telomerase activities were comparable, ranging from 0.4 to 1.0 in ulcerative colitis and from 0.3 to 0.6 in Crohn's disease and averaging 0.4 in controls. Apparently low telomerase activities are present in the mucosa of all patients and the enzyme is not yet upregulated in the potentially premalignant state of active ulcerative colitis, dismissing its prognostic value as an early tumor marker for this disorder.

Association between the C3435T MDR1 gene polymorphism and susceptibility for ulcerative colitis.

BACKGROUND & AIMS: The human multidrug resistance 1 (MDR1) gene product P-glycoprotein is highly expressed in intestinal epithelial cells, where it constitutes a barrier against xenobiotics. The finding that mdr1a knockout mice develop a form of colitis that is similar to ulcerative colitis, which can be prevented by antibiotics, indicates a barrier function for P-glycoprotein against the invasion of bacteria or toxins. Because the MDR1 single nucleotide polymorphism C3435T is associated with lower intestinal P-glycoprotein expression, we tested whether this polymorphism predisposes to development of ulcerative colitis. METHODS: Allele frequencies and genotype distributions of the C3435T single nucleotide polymorphism were investigated in 149 patients with ulcerative colitis, 126 patients with Crohn's disease, and sex-matched healthy controls. RESULTS: Significantly increased frequencies of the 3435T allele and the 3435TT genotype were observed in patients with ulcerative colitis compared with controls (3435T: P = 0.049; odds ratio, 1.4; 95% confidence interval, 1.02-1.94; 3435TT: P = 0.045; odds ratio, 2.03; 95% confidence interval, 1.04-3.95). In contrast, frequencies of the T allele and the TT genotype were the same in patients with Crohn's disease as in controls (P = 0.66 and P = 0.59, respectively). In comparison to 998 non-sex-matched controls, the effect for the TT genotype in ulcerative colitis patients was more pronounced (P = 0.0055; odds ratio, 2.1). CONCLUSIONS: The higher frequency of the 3435TT genotype in patients with ulcerative colitis corroborates the findings from the mdr1a knockout mice. The results support the notion that P-glycoprotein plays a major role in the defense against intestinal bacteria or toxins. Impairment of barrier function in 3435TT subjects could render this genotype more susceptible to the development of ulcerative colitis.