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Biomedical subjects

G Treiber

Publications and source records attributed to G Treiber.

At least 19 recordsLinked to original sources

Impact of biomarkers on disease survival and progression in patients treated with octreotide for advanced hepatocellular carcinoma.

BACKGROUND: Current determination of prognosis for advanced hepatocellular carcinoma (HCC) is mainly based on clinical assessment. We aimed to determine the impact of biomarkers as predictive factors for HCC progression and survival during octreotide-based treatments. PATIENTS AND METHODS: We included patients who had been prospectively randomised to receive either octreotide (30 mg) alone monthly (n = 39) or in combination with rofecoxib (up to 50 mg bid daily, n = 32) for a minimum of 6 months, or until death occurred. RESULTS: Overall median survival (154 days) and median time to progression (94 days) were not different for both treatments and the biomarkers investigated (VEGF-A, IGF-1, PGE-2, ET-A) were similarly distributed amongst treatment groups. Combined univariate group analysis revealed that survival was decreased for an uptake ratio of > 2 on initial octreoscan (P = 0.05); baseline serum VEGF-A and IGF-1 were further significantly associated with survival. On multivariate analysis, uncorrected serum VEGF-A appeared to be the most significant predictor for tumor progression and survival. CONCLUSIONS: Biomarkers, in addition to established tumor markers, are independent predictors of tumor progression and survival in patients with advanced HCC treated with octreotide. Furthermore, the involvement of VEGF-A implies the inhibition of angiogenesis as a potential mechanism of action for this drug.

Aged↗

Effects of low-dose aspirin on gastric erosions, cyclooxygenase expression and mucosal prostaglandin-E2 do not depend on Helicobacter pylori infection.

BACKGROUND: The mechanisms by which Helicobacter pylori and low-dose aspirin induce gastric damage are not completely elucidated. AIM: To evaluate the effects of low-dose aspirin on gastric damage, mucosal prostaglandin-E(2) levels and cyclooxygenase-enzyme expression in relation to the H. pylori status. METHODS: Twenty healthy volunteers (H. pylori positive, n = 10; H. pylori negative, n = 10) received aspirin 100 mg/die for 1 week. At days 0, 1, 3 and 7, gastric mucosal lesions were studied by oesophagogastroduodenoscopy and histology. COX-1 and COX-2 were determined by immunohistochemistry and reverse-transcriptase polymerase chain reaction, and mucosal prostaglandin-E(2) levels by enzyme-linked immunosorbent assay. Nine H. pylori-positive subjects repeated the protocol after H. pylori eradication. RESULTS: All groups developed a similar number of erosions. COX-1 and COX-2 expression, as well as mucosal prostaglandin-E(2) levels were not influenced by H. pylori status and aspirin medication. Helicobacter pylori-negative and H. pylori-eradicated subjects who developed aspirin-induced erosions had significant lower pre-treatment antral prostaglandin-E(2) levels than those without erosions (3.6 ng/microg vs. 6.3 ng/microg protein and 3.6 ng/microg vs. 6.0 ng/microg protein, respectively, P < 0.01 Mann-Whitney U-test). CONCLUSIONS: In healthy subjects, low-dose aspirin for 1 week does neither affect cyclooxygenase expression nor mucosal prostaglandin-E(2) levels. Antral prostaglandin-E(2)-basal levels appear to be critical for development of aspirin-induced gastric damage in subjects without H. pylori infection.

Adult↗

The effect of single-dose naproxen on eicosanoid formation in human gastroduodenal mucosa.

BACKGROUND: In animal studies, aspirin and non-aspirin non-steroidal anti-inflammatory drugs contribute to gastroduodenal damage via cyclo-oxygenase inhibition and consecutive leucotriene formation (COX-LOX eicosanoid shunt). AIM AND METHODS: Ten Helicobacter pylori-negative healthy volunteers received a single dose of 500 mg naproxen to address two questions: (i) is there a crosstalk between eicosanoids before medication in the human gastroduodenal mucosa and (ii) can we demonstrate a COX-LOX shunt following single-dose naproxen? RESULTS: Significant correlations in the stomach mucosa before medication were obtained between leucotriene B4 (LTB4) and thromboxane B(2) (TxB(2); r = -0.38, P = 0.05), as well as LTB4 and prostaglandin E(2) (PGE(2); r = 0.71, P < 0.0001). In serum, a >90% inhibition of TxB(2) and PGE(2) occurred within 30 min of naproxen administration. In gastric mucosa, a significant decrease of TxB(2) occurred already at 15 min and preferably in the antrum. For LTB4 there was a non-significant trend towards a transient increase. Mucosal PGE(2) was unchanged in all regions; transcript levels of both cyclo-oxygenases/5-lipoxygenase were unaffected (except for a trend of increasing cyclo-oxygenase-2 in the corpus). CONCLUSIONS: Baseline correlations between LTB4-TxB(2) and LTB4-PGE(2) reflect a crosstalk between these eicosanoids. A COX-LOX shunt; however, cannot be demonstrated following single-dose naproxen in a low-risk population.

Adult↗

Diagnostic and therapeutic impact of double-balloon enteroscopy.

BACKGROUND AND STUDY AIMS: Double-balloon enteroscopy (DBE) is a new endoscopic method for examining the small intestine. Most reports of DBE have been from Japan, and very few data on this new technique have been reported by centers outside Japan. The aim of the present study was to determine the diagnostic yield of DBE, measure the frequency of management changes made on the basis of the results, and evaluate the clinical outcome for patients undergoing the procedure. PATIENTS AND METHODS: All patients undergoing DBE using a Fujinon enteroscope (length 200 cm, diameter 8 mm) during a 11-month period were studied. All of the patients had previously undergone esophagogastroduodenoscopy and colonoscopy. They underwent small-bowel cleansing on the day before the procedure using a standard colon lavage solution. RESULTS: Seventy DBE procedures were carried out in 53 patients (34 men, 19 women; mean age 60 years, range 24 - 80) by the oral route in 46 cases and the anal route in 24. The indications for the examination were gastrointestinal bleeding (n = 29), suspected Crohn's disease (n = 6), abdominal pain (n = 4), polyp removal or evaluation in polyposis syndromes (n = 6), chronic diarrhea (n = 4), and surveillance or tumor search (n = 4). The mean duration of the procedure was 72 min (range 25 min - 3 h). The mean radiation exposure was 441 dGy/cm (range 70 - 1462), and the mean depth of small-bowel insertion was 150 cm (range 1 - 470 cm). It was possible to evaluate the entire small bowel in four patients (8 %). A new diagnosis was obtained in 26 of the 53 patients (49 %). The findings in the 70 procedures were angiodysplasia (n = 13), ulcerations or erosions (n = 5), jejunitis or ileitis (n = 5), tumors (n = 5), stenosis (n = 4), polyps (n = 5), lymphangiectasias (n = 4), Crohn's disease (n = 4), and normal (n = 17). DBE resulted in a therapeutic intervention (endoscopic, medical or surgical, excluding blood transfusions) in 57 % of the patients (30 of 53). The only complication (1.4 %) observed was one case of intraprocedural postpolypectomy bleeding, which resolved with injection of epinephrine. CONCLUSION: In almost two-thirds of the patients examined, DBE was clinically useful for obtaining a new diagnosis and starting new treatments, changing existing treatments, carrying out surgical intervention, or providing therapeutic endoscopy. DBE is a useful and safe method of obtaining tissue for diagnosis, providing hemostasis, and carrying out polypectomy.

Adult↗

Dyspeptic symptoms associated with Helicobacter pylori infection are influenced by strain and host specific factors.

BACKGROUND: Dyspepsia can be associated with H. pylori infection. AIM: To assess dyspeptic symptoms and potentially influencing factors before and up to 6 months following successful H. pylori eradication therapy. METHODS: Prospective cohort study involving H. pylori positive subjects from ambulatory or hospitalized care. Main outcome measures were symptoms during baseline and follow-up, the proportion of symptom-free patients, and symptom scores. RESULTS: After successful eradication, the summary score of all dyspeptic symptoms decreased and during follow-up, the proportion of symptom-free patients was higher in the group with peptic ulcers (69.4% vs. 40.9%, P < 0.0001) than with functional dyspepsia (FD). Regardless of diagnosis, virulent strains of H. pylori were associated with a higher prevalence of epigastric pain before treatment: absolute risk-difference (ARD) with Oip-A: 18.2%, Odds Ratio (OR) 2.35 [1.3-4.2, 95%-CI], P = 0.01; with Cag-A: 24.6%, OR 2.81 [1.6-5], P = 0.01. Low-dose aspirin in part was a major risk factor in FD for previous weight loss bdfore study entry. Post-treatment, non-ulcer patients were more likely to suffer from distention/bloating. Likewise, alcohol induced persistence of nausea and vomiting in this population. CONCLUSIONS: Dyspeptic symptoms in H. pylori infected patients are more common with virulent strains. Symptoms are more likely to persist despite successful eradication if patients initially harboured virulent strains or concomitant aspirin or alcohol intake are present. In one-third of peptic ulcer patients, symptoms will not be cured 3 months after therapy.

Adult↗

What constitutes failure for Helicobacter pylori eradication therapy?

Apart from patients with peptic ulcer disease, the use of eradication therapy for Helicobacter pylori infection has been extended to patients with H pylori-positive dyspepsia and conditions at risk for gastric cancer. Standard treatments comprise a proton pump inhibitor plus two antibiotics for at least one week. The main factors leading to treatment failure are noncompliance and antibiotic resistance. Provided the patient is sufficiently informed about possible side effects, discontinuation of the newer triple therapies has become rare. The prevalence of antibiotic resistance varies considerably among different geographic regions, reflecting the habits of prescription of these antibiotics for other indications. Largely, it ranges from 1% to 15% for macrolides, and from 7% to 60% for nitroimidazoles. With nitroimidazole resistance, treatment failure occurs in only less than 50%; with macrolide resistance, by contrast, in more than 50% of the cases. Furthermore, bacterial and host-related factors (Cag A virulence factor, grade of inflammation) contribute to eradication success. In case of treatment failure, post-therapeutic resistance is frequent. Important principles for the choice of second-line treatment are: not to repeat an antibiotic with potential post-therapeutic resistance, and to ensure sufficient acid suppression.

Algorithms↗

[Helicobacter pylori--2002].

Treatment recommendations for H. pylori infection are peptic ulcer disease, MALT lymphoma, atrophic gastritis and following gastric cancer resection as well as first degree relatives of gastric cancer patients. Advisable situations are functional dyspepsia, before introduction of NSAID's or intended long-term proton-pump inhibitor treatment. It is thought that eradication therapy is not associated with gastro-esophageal reflux disease and does not enhance NSAID induced peptic ulcer healing. Therapy should be given as a package which considers first and second line eradication therapies together; in uncomplicated duodenal ulcer patients, eradication therapy does not need to be followed by further antisecretory treatment. First line therapy should be with triple therapy using a proton pump inhibitor (PPI), combined with clarithromycin and amoxycilline or metronidazole. Second-line therapy should use a quadruple therapy with a PPI, bismuth, metronidazole and tetracycline. Where bismuth is not available, second line therapy should be with a PPI triple therapy. If second line quadruple therapy fails in primary care, patients should be referred to the specialist and handled on a case by case basis. Successful eradication should always be confirmed by urea breath test (UBT), or endoscopy-based tests if endoscopy is clinically indicated. Stool antigen test is the alternative if UBT is not available. A 'test and treat' approach based on non-invasive testing can be offered to adult patients presenting in primary care with persistent dyspepsia under the age of 45 years (the age cut-off may vary locally), having excluded those with predominantly gastroesophageal reflux disease (GERD) symptoms, NSAID users, and patients with alarm symptoms.

Anti-Bacterial Agents↗

Impact of furazolidone-based quadruple therapy for eradication of Helicobacter pylori after previous treatment failures.

BACKGROUND: One week of quadruple therapy including metronidazole is recommended for Helicobacter pylori treatment failures after first line therapy regardless of resistance status. This study investigated whether a quadruple regimen containing furazolidone could be effective as a third-line (salvage) therapy. METHODS: All patients with previous H. pylori treatment failure after a clarithromycin-metronidazole +/- amoxicillin combination plus acid suppression were given lansoprazole 30 mg twice a day (bid), tripotassiumdicitratobismuthate 240 mg bid, tetracycline 1 g bid, metronidazole 400 mg (PPI-B-T-M) three times a day (tid) for 1 week. In the case of treatment failure with this second-line therapy, the same regimen was applied for 1 week except for using furazolidone 200 mg bid (PPI-B-T-F) instead of metronidazole (sequential study design). RESULTS: Eighteen consecutive patients were treated with PPI-B-T-M. Eleven of those 18 remained H. pylori positive (38.9% cured). Pretherapeutic metronidazole resistance was associated with a lower probability of eradication success (10% vs. 75%, p=.04). Ten of these 11 patients agreed to be retreated by PPI-B-T-F. Final cure of H. pylori with PPI-B-T-F was achieved in 9/10 patients (90%) nonresponsive to PPI-B-T-M. CONCLUSIONS: In the presence of metronidazole resistance, PPI-B-T-M as a recommended second-line therapy by the Maastricht consensus conference achieved unacceptable low cure rates in our metronidazole pretreated population. In this population, metronidazole based second-line quadruple therapy may be best suited in case of a metronidazole-free first line-regimen (e.g. PPI-clarithromycin-amoxicillin) or a low prevalence of metronidazole resistance. Furazolidone in the PPI-B-T-F combination does not have a cross-resistance potential to metronidazole and is a promising salvage option after a failed PPI-B-T-M regimen.

Anti-Bacterial Agents↗

Systemic treatment of hepatocellular carcinoma.

Systemic treatment for hepatocellular carcinoma is indicated in locally advanced or metastatic disease. Monochemotherapies have yielded unsatisfactory results with response rates of around 20% but survival is often not improved. Polychemotherapies may induce complete responses but have substantial toxicity and are limited to selected patients with preserved liver function. Hormonal treatment with tamoxifen is ineffective while megestrol has shown an improvement in quality of life. Octreotide can be given even in cases of impaired liver function, has also a favorable side effect profile and can lead to disease stabilization. Adjuvant therapy with interferon is indicated after successful liver resection or transplantation in patients with chronic viral hepatitis, the role of interferon in other indications or in combination with chemotherapy remains to be determined.

Antineoplastic Agents↗

[Therapy of Helicobacter pylori infection].

H. pylori eradication remains standard treatment for peptic ulcer disease. Until now, other indications like non-ulcer dyspepsia, reflux esophagitis, or concomitant medication with non-steroidal antirheumatics are not approved according to actual guidelines and these patients should be managed on an individual basis only. One week triple therapy consisting of a proton-pump inhibitor (PPI), a macrolide antibiotic (clarithromycin), and a imidazole antibiotic (metronidazole) or amoxicillin, given bid. Quadruple therapy including PPI, bismuth, tetracycline and metronidazole should be reserved to eradication failures.

Anti-Bacterial Agents↗

Influence of age on the steady state disposition of drugs commonly used for the eradication of Helicobacter pylori.

BACKGROUND: The success of eradication therapy for Helicobacter pylori might be affected by the age of patients. AIM: To investigate whether disposition of drugs commonly used for H. pylori eradication is age-dependent. METHODS: Trough steady state serum levels of lansoprazole or ranitidine, amoxycillin, clarithromycin and metronidazole were monitored in 232 patients during the last dosing interval of a 5-day quadruple H. pylori eradication regimen. Detailed pharmacokinetic analysis was performed in 28 patients. RESULTS: Linear correlations between age and trough serum levels were observed with lansoprazole (r=0.25; P=0.002), ranitidine (r=0. 38; P=0.001) and clarithromycin (r=0.36; P < 0.0001). These associations were also inversely dependent of creatinine clearance for ranitidine (r=0.36; P=0.001) and clarithromycin (r=0.30; P < 0. 0001). Multiple linear regression revealed age as an important factor influencing trough serum levels of lansoprazole, clarithromycin and ranitidine. There were significant inverse relationships between creatinine clearance and area under curve of ranitidine (r=0.88; P < 0.0001) and amoxycillin (r=0.56; P=0.002). Multiple linear regression revealed serum creatinine as the most important factor influencing the area under curve of ranitidine, clarithromycin and amoxycillin. CONCLUSIONS: Age per se has little influence on pharmacokinetics of amoxycillin and ranitidine, which depend more on age-dependent decline in renal function. The influence of age, but not renal function was established for lansoprazole. Age and renal function have independent impacts on clarithromycin disposition.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Treating H. pylori shorter than one week--a real future perspective?

BACKGROUND: We assessed the current impact of H. pylori eradication therapies with a short (4-6 days) and very short (< or = 3 days) duration of antibiotic treatment because of possible advantages in terms of costs and side effects over standard one-week triple therapy. METHODS: The literature was reviewed and 35 studies analyzed, leading to a total of 51 treatment regimens with 2177 patients. RESULTS: Cumulative per-protocol H. pylori eradication rates were 61.3%, 75.2%, and 79.4% for dual, triple and quadruple therapies, respectively. Dual therapy was inferior to triple and quadruple regimens (p < 0.001), while the difference between triple and quadruple therapy did not reach statistical significance. Subgroup analysis of all triple therapies containing macrolides and imidazoles resulted in a success rate of 84.1% (vs. 62.1% for other triple therapies, p < 0.0001). Decreasing the treatment duration to 3 days or less resulted in a loss of efficacy for both bismuth-based quadruple therapy with tetracycline and imidazoles (90.3% vs. 65%, p < 0.0001) and for triple therapy with macrolides and amoxicillin (70.3% vs. 31.2%, p < 0.0001). This does not hold true for triple therapy containing imidazoles and macrolides (84.5% vs. 83.6%, not significant). Regardless of the duration of therapy quadruple regimes with macrolides/imidazoles/amoxicillin achieved an eradication rate of 91.9%. CONCLUSIONS: Preliminary data suggest that the short-term combination of proton pump inhibitors with 2 antibiotics (macrolides and imidazoles) with/without amoxicillin may be as effective as standard one week triple therapies, even for treatment durations of 3 days or less. The combination of proton pump inhibitors with bismuth, tetracycline and imidazoles appears to be equally effective, if given for at least 4 days.

Anti-Bacterial Agents↗