Prospective multicentre clinical study on inter- and intrapatient genetic variability for antimicrobial resistance of Helicobacter pylori.

OBJECTIVES: We report on a large prospective, multicentre clinical investigation on inter- and intrapatient genetic variability for antimicrobial resistance of Helicobacter pylori. METHODS: Therapy-naive patients (n = 2004) who had undergone routine diagnostic gastroscopy were prospectively included from all geographic regions of Austria. Gastric biopsy samples were collected separately from antrum and corpus. Samples were analysed by histopathology and real-time PCR for genotypic resistance to clarithromycin and quinolones. Clinical and demographic information was analysed in relation to resistance patterns. RESULTS: H. pylori infection was detected in 514 (26%) of 2004 patients by histopathology and confirmed in 465 (90%) of 514 patients by real-time PCR. PCR results were discordant for antrum and corpus in 27 (5%) of 514 patients, indicating inhomogeneous infections. Clarithromycin resistance rates were 17% (77/448) and 19% (84/455), and quinolone resistance rates were 12% (37/310) and 10% (32/334) in antrum and corpus samples, respectively. Combination of test results per patient yielded resistance rates of 21% (98/465) and 13% (50/383) for clarithromycin and quinolones, respectively. Overall, infection with both sensitive and resistant H. pylori was detected in 65 (14%) of 465 patients. CONCLUSIONS: Anatomically inhomogeneous infection with different, multiple H. pylori strains is common. Prospective clinical study design, collection of samples from multiple sites and microbiologic methods that allow the detection of coinfections are mandatory for collection of reliable data on antimicrobial resistance patterns in representative patient populations. (ClinicalTrials.gov identifier: NCT02925091).

Efficacy and tolerability of pantoprazole compared with misoprostol for the prevention of NSAID-related gastrointestinal lesions and symptoms in rheumatic patients.

AIM: To compare the efficacy and tolerability of pantoprazole 20 mg once daily (o.d.) with misoprostol 200 microg twice daily (b.i.d.), administered for 6 months to rheumatic patients who required long-term therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) and who were at increased risk of developing gastrointestinal lesions. METHODS: This randomized, double-blind, multicenter, parallel group comparison study was performed with rheumatic patients (n = 515) who were likely to take NSAIDs continuously for at least 6 months. Patients were 55 years or older, at risk to develop gastrointestinal lesions, had less than five erosions/petechiae in the stomach and duodenum, no ulcers, no reflux esophagitis (endoscopy-proven), and gastrointestinal symptoms of at most moderate intensity. A minimum daily dose was defined for NSAIDs (COX-2 inhibitors were not available at the time). Patients were randomized to take either pantoprazole 20 mg o.d. (n = 257) or misoprostol 200 microg b.i.d. (n = 258) for 6 months while continuing NSAID therapy. Endoscopy was performed at baseline, 3, and 6 months. RESULTS: Pantoprazole was superior to misoprostol (p < 0.001) with regard to 'therapeutic failure' (occurrence of a peptic ulcer, ten or more erosions/petechiae in the stomach/duodenum, reflux esophagitis, severe gastrointestinal symptoms, and/or 'likely' or 'definitely' related adverse event leading to study termination). Estimated remission rates at 3 and 6 months (Kaplan-Meier life-table analysis) were, respectively, 93 and 89% (pantoprazole) and 79 and 70% (misoprostol). Pantoprazole was superior to misoprostol (p = 0.005) with regard to 'endoscopic failure' (occurrence of a peptic ulcer, ten or more erosions/petechiae in the stomach/duodenum, or reflux esophagitis) after 6 months. Estimated remission rates at 3 and 6 months were, respectively, 98 and 95% (pantoprazole) and 95 and 86% (misoprostol). Patients discontinuing the study early due to adverse events 'likely' or 'definitely' related to the study drug accounted for 13/257 (5%) in the pantoprazole and 33/258 (13%) in the misoprostol treatment groups. CONCLUSION: Pantoprazole 20 mg o.d. is superior to misoprostol 200 microg b.i.d. in the prevention of NSAID-induced gastrointestinal lesions and symptoms in patients on continuous long-term treatment with NSAIDs due to rheumatic diseases and at risk to develop such lesions or symptoms.

Triple therapy with sucralfate, amoxycillin and metronidazole for healing duodenal ulcer and eradicating Helicobacter pylori infection.

METHODS: Seventy-seven chronic duodenal ulcer patients (50 male) were entered into this study. Treatment was started with sucralfate suspension (2 g b.d.) for 8 weeks. After 2 weeks the patients also received 750 mg amoxycillin t.d.s. plus 500 mg metronidazole t.d.s. for 12 days. Endoscopy with six antral biopsies (urease test, Gram staining, culture and histology) was performed before commencement of sucralfate therapy, 4 weeks after the end of antibiotic therapy, and during the follow-up examinations at 6 and 12 months. RESULTS: Seven patients were excluded prematurely from the study. Helicobacter pylori in five patients had primary resistance to metronidazole and these patients were also excluded. The ulcer healing rate 4 weeks after the end of antibiotic therapy was 92% and the H. pylori eradication rate was 82% (all per protocol). In all patients who were still H. pylori-positive, the bacterium became resistant to metronidazole and histologically the inflammatory state of the mucosa was the same as before treatment. All H. pylori-eradicated patients (n = 53) were re-examined after 6 and 12 months; no ulcer recurrence was observed and each time only one reinfection was found. CONCLUSIONS: In an open study, sucralfate with amoxycillin and metronidazole appeared to act together to eradicate H. pylori infection and to speed duodenal ulcer healing.

Malignant bile-duct obstruction: experience with self-expanding metal endoprostheses (Wallstents) in Austria.

Fifty-two patients in nine Austrian hospitals were treated with biliary self-expanding metal endoprostheses (Wallstents) for malignant biliary obstruction, and followed up retrospectively using questionnaires, answered by the endoscopists. Stent placement was successful in all patients. The technical failure rate at the first attempt was 7.7%, and stenting-associated mortality was 3.8% due to mispositioning of stents, leading in two cases to death. The 30-day mortality was 13.5%, and early complications occurred in 15.4%. The median survival was 216 days, and the median stent patency was 291 days. During follow-up, stent occlusion was observed in ten patients, acute cholangitis in 12 patients, acute pancreatitis in three patients, acute cholecystitis in one patient, and duodenal ulceration due to stent erosion in one patient. Routine use of biliary self-expanding metal endoprostheses by averagely experienced endoscopists can be recommended. Attention has to be paid to the correct placement of the guidewire and stent.

[Results following endoscopic paravasal long-term sclerosing of esophageal varices]. / Ergebnisse nach endoskopischer paravasaler Langzeitsklerosierung von Osophagusvarizen.

Our experiences confirm that with endoscopical paravasal longterm sclerosing of esophageal varices the incidence of recidive bleeding can be clearly reduced and the probability of survival of the patients treated with this method can be improved. Recidive bleeding occurred in 38% of those patients treated with longterm sclerosing, in a conservatively treated group, on the other hand, in 61% of the cases. At the end of the observation period (January 1980 to December 1984) two thirds of the patients treated with sclerosing remained alive, in the control group, however, only one half of 71 patients survived. This favourable result can be attributed to reduced mortality because of bleeding, since the mortality of coma hepaticum and of other rare causes of death is nearly equal in both groups of patients.

[Endoscopic palliative drainage of the bile ducts]. / Endoskopische palliative Gallengangsdrainage.

Initial results of palliative endoscopic retrograde drainage of the common bile duct are reported. In 12 out of 19 patients the treatment was successful (63% cases). In every case the serum bilirubin level quickly decreased to normal values. The life span of the endoprostheses lasted on average for 3 months. No fatal complications occurred in connexion with prosthesis implantation. Endoscopic drainage of the common bile duct in patients with an inoperable tumour of the biliary tract represents an alternative procedure to palliative surgery in the management of malignant occlusion icterus.

[Endoscopic fistulotomy in choledocholithiasis]. / Endoskopische Fistulotomie bei Choledocholithiasis.

In 9 cases of choledocholithiasis and 2 cases of endoscopically determined stenosis of the papilla in which an EPT could not be successfully performed it was possible to carry out a prepapillary choledochoduodenal fistula by means of endoscopy. Subsequently the fistula was split in the cranial direction using a papillotome, i.e. a fistulotomy was performed. The choledochal concrements disappeared spontaneously and the patients recovered successfully. In 4 further cases with an occlusion icterus, but with narrow ductus choledochus the common bile duct could not be cannulated. The endoscopic fistulotomy is only indicated when the common bile duct is dilated and if prior to the procedure and after failure of ERCP the indication for a surgical intervention is established through sonography or even better through PTC.

[Long-term results after endoscopic papillotomy]. / Langzeitergebnisse nach endoskopischer Papillotomie.

A long-term control study after endoscopic papillotomy was performed in 102 patients at least 12 months after the procedure. 14 patients were no longer alive, from those only one patient died due to biliary problems. Complications occurred in 10 patients (9,8%). There was no cholangitis, but 2 cases of an acute cholecystitis some time after papillotomy. Therefore a cholecystectomy after papillotomy is suggested in the interval.

[Effect of ciclotropium bromide on pressure in the human common bile duct]. / Die Wirkung von Ciclotropiumbromid auf den Druck im menschlichen Gallengangsystem.

The effect of a new anticholinergic drug, ciclotropium bromide, on artificially induced pressure elevations in the common bile duct is reported. The endoscopic manometry allows a precise pressure measurement in the biliary system. For the artificial pressure elevation an X-ray contrast medium was injected into the common bile duct until the pain threshold was reached. In each patient a statistically significant pressure reduction accompanied by pain relief was reached. The method used shows the drug effects by objective measurement of the pressure reduction and the subjective indication of the pain relief.

[Endoscopic manometry in the common bile duct]. / Endoskopische Manometrie im Gallengang.

Reproducible results were obtained by endoscopic transpapillary pressure measurements with the help of a constantly perfused catheter. Manometric measurements were performed in 51 patients without any premedication. 14 patients with a normal biliary system were compared with 17 patients after cholecystectomy, 14 patients with stones in the common bile duct and 6 patients after papillotomy. Although there were significant differences in the diameter of the common bile duct in the four groups, only the papillotomized patients demonstrated a distinct change of the pressure in the bile duct. In these patients almost no pressure gradient existed between the biliary ducts and the duodenum. On the other hand, there was an increase in intraluminal pressure in the 2 patients with papillary stenosis. Endoscopic manometric measurements in the common bile duct are indicated to obtain reliable data on stenosis of the papilla duodeni, insufficient papillotomy or recurrent stenosis.

[Experience with endoscopic papillotomy (author's transl)]. / Erfahrungen mit der endoskopischen Papillotomie.

The results of 64 endoscopic papillotomies (EPT) are reported. When precautions are taken the EPT is a highly effective procedure of low risk. The minimal stress for the patient, the high accuracy and the low number of complications guarantee this method a prominent place in the treatment of bile duct illnesses. Control examinations of 30 patients to 12 months after operation proved all patients symptom-free and neither biochemical nor clinical evidence of cholangitis or other complications.