Sotirios Georgopoulos

Fenestrated and Branched Endografts for the Treatment of Thoracoabdominal Aortic Aneurysms: A Systematic Review

Purpose: To offer a critical review of the current literature on the use of fenestrated and branched stent-grafts in patients with thoracoabdominal aortic aneurysms (TAAA). Methods: A thorough search of the English-language literature published between January 2000 and September 2009 identified reports of endovascular procedures using fenestrated and/or branched endografts as the intended repair strategy in patients with TAAA. Studies were selected based on specific inclusion criteria: (1) >3 high-risk patients with preoperative diagnosis of TAAA, (2) the intended treatment strategy was an endovascular repair using a fenestrated or branched endograft or both, and (3) patient demographics and outcome data (technical success rate, 30-day mortality, and follow-up length) were clearly stated. From 47 articles initially identified, 7 studies were included in the statistical analysis encompassing 155 patients (mean age 74.4 years, range 41–86) with TAAA averaging 69.2 mm in diameter. The mean follow-up was 11.8 months, and the majority of patients had Crawford type IV aneurysms. Outcome measures of eligible studies were tabulated and then analyzed cumulatively. Results: Technical success was achieved in 94.2% (n = 146) of the 155 patients. Twenty-three (18.4%) primary endoleaks were reported. The 30-day mortality was 7.1% (n = 11), while the 1-year survival rate was 82.6% (n = 128). Three (1.9%) patients developed permanent paraplegia and 2 (1.3%) developed permanent paraparesis; renal failure was reported in 9 (5.8%). Overall follow-up mortality was 16.1% (n=25). Conclusion: Endovascular treatment with fenestrated or/and branched stent-grafts is a new therapeutic option with encouraging results for patients considered unfit for conventional open repair. However, prolonged follow-up studies are needed in order to draw robust conclusions.

Effectiveness of two quadruple, tetracycline‐ or clarithromycin‐containing, second‐line, Helicobacter pylori eradication therapies

There are no guidelines on second‐line therapies for Helicobacter pylori eradication failures of omeprazole–clarithromycin–amoxicillin triple therapy.

Hypergastrinemia Is Associated with Increased Risk of Distal Colon Adenomas

Background/Aims:Helicobacter pylori infection is a recognized cause of hypergastrinemia, but the association of blood gastrin levels with colonic adenomas (CAs) is controversial. The aim of this study is to investigate if hypergastrinemia, H. pylori infection and/or cagA protein are risk factors for CAs. Methods: In this prospective case-control study, fasting serum samples from 78 consecutive patients with CAs and 78 demographically matched colonoscopy-negative controls were assayed for anti-H. pylori immunoglobulin G, cagA protein and serum gastrin levels. Multivariate analysis was performed to identify risk factors for colon adenomas. Results: Though prevalence of H. pylori antibodies was not significantly different, the prevalence of cagA protein was significantly higher in patients with adenomas (42.3%) as compared with controls (25.6%, p < 0.03). Mediangastrin levels were significantly higher in patients with CAs (55, 20–975 pg/ml) than in controls (45.2, 23–529 pg/ml) (p < 0.001). Hypergastrinemia (>110 pg/ml) was commoner in patients with CAs than in controls (29.5 vs. 11.5%, p = 0.006) and was the only independent risk factor for adenomas (odds ratio 3.2, 95% CI 1.4–7.5) by multivariate analysis, but not H. pylori infection or cagA positivity. There was a significant association of hypergastrinemia and distal distribution of adenomas (p < 0.002). Conclusions: Our study shows that hypergastrinemia is a risk factor for CAs, especially of the distal colon.

Factors that may affect treatment outcome of triple Helicobacter pylori eradication therapy with omeprazole, amoxicillin, and clarithromycin.

Factors affecting Helicobacter pylori eradication rate with omeprazole (OME), clarithromycin (CL), and amoxicillin (AMO) have not been extensively studied. We have investigated the effect of age, sex, smoking, ulcer disease, compliance with therapy, H. pylori colonization density, degree and activity of antral gastritis, the coexistence of corpus gastritis, and the presence of lymphoid follicles on H. pylori eradication rate. We studied 80 consecutive H. pylori-positive patients, with duodenal ulcer (N = 35) or nonulcer dyspepsia (N = 45) treated with OME 20 mg, CL 500 mg, and AMO 1 g, each given twice daily for 10 days. H. pylori was eradicated in 71/80 (88.8%, 95% CI 82–96%) patients. The regimen failed to eradicate the only strain (1.8%, 95% CI 0–5.2%) that was clarithromycin resistant. Multivariate discriminant analysis showed that two histological variables (Wilks λ = 0.74, χ2 = 23.41, df = 2, P < 0.001), absence of lymphoid follicles in routine gastric biopsies (F = 13.63, P < 0.001) and coexistence of antral and body gastritis (F = 13.68, P < 0.001), significantly increased H. pylori eradication rate. No other factor examined predicted H. pylori eradication with this regimen. Our data suggest that body gastritis is a positive and presence of lymphoid follicles in routine gastric biopsies is a negative predictive factor of treatment outcome with the omeprazole, clarithromycin, and amoxicillin regime.

Current options for the treatment of Helicobacter pylori.

Indroduction: Treatment of Helicobacter pylori (H. pylori) infection is crucial for prevalent diseases management, including gastritis, peptic ulcer and gastric cancer, whereas novel extradigestive causal associations are increasingly being recognized. Despite long-standing efforts, there is not as yet an optimal empirical therapy to eradicate H. pylori. Areas covered: In the present article the authors review current options for H. pylori eradication. Advantages and disadvantages of each of the recommended regimens, and the perspectives for their rational use in clinical practice, are critically discussed. Expert opinion: The continuous rising of antimicrobial resistance has accounted for the declined efficiency of standard triple therapies, yielding < 70% eradication in most countries. Alternative first-line strategies have been proposed and largely validated and are now replacing standard-of-care therapies in areas with a high incidence of clarithromycin-resistance (> 20%). Such treatments include the bismuth-containing quadruple therapy, concomitant, sequential and levofloxacin-based regimens, the later mainly designated, together with rifabutin-based therapies as second-line/rescue options. Clinicians should be aware of the local resistance pattern and maintain first-line eradication to levels > 90% (per-protocol efficacy). This will prevent both exposing the patient to repeated treatments and spreading of secondary antimicrobial resistance. In the future, perspectives of tailored therapy and a prophylactic vaccine will obviate any treatment concern.

Clinical Evaluation of a Ten-Day Regimen with Esomeprazole, Metronidazole, Amoxicillin, and Clarithromycin for the Eradication of Helicobacter pylori in a High Clarithromycin Resistance Area

Increasing clarithromycin resistance reduces Helicobacter pylori eradication rates with conventional triple regimens. We evaluated effectiveness and safety of a 10‐day‐quadruple nonbismuth containing regimen, as first‐line treatment or second‐line treatment (after conventional triple) for H. pylori, and assessed impact of antibiotic resistance on treatment success.

Evaluation of a Four-drug, Three-antibiotic, Nonbismuth–containing “Concomitant” Therapy as First-line Helicobacter pylori Eradication Regimen in Greece

Background:  The eradication rates of Helicobacter pylori (H. pylori) with standard treatments are decreasing worldwide as in Greece. Studies with new antibiotic combinations are needed to find better methods of eradication. Therefore, the aim of this study was to evaluate efficacy and tolerability of a 10‐day, four‐drug, three‐antibiotic, nonbismuth–containing concomitant regimen.

Treatment of Helicobacter pylori infection: Meeting the challenge of antimicrobial resistance

Treatment of Helicobacter pylori (H. pylori) infection is paramount for the management of prevalent gastrointestinal disorders including peptic ulcer disease and gastric cancer. Due to the wide increase in prevalence of H. pylori resistance to antibiotics, clarithromycin-based triple therapies are not any more suitable for unconditional empiric use, and should not be recommended, unless local resistance to this antibiotic is low (< 20%). Alternative strategies have been proposed to overcome the issue of increasing clarithromycin resistance, and some of them are already implemented in clinical practice. These comprise: (1) adoption of novel, more effective, empirical treatments: bismuth quadruple, sequential, non-bismuth quadruple (concomitant), dual-concomitant (hybrid), and levofloxacin-based regimens, the latter mainly designated as second-line/rescue options; (2) perspectives for a susceptibility-guided (tailored) therapeutic approach based on culture-free molecular testing methods; and (3) adjunct use of probiotics to improve eradication rates. The present article is aimed to provide a comprehensive overview of current and emerging strategies in the treatment of H. pylori infection, focusing on the challenge of antimicrobial resistance.

Treatment of Helicobacter pylori infection: Past, present and future

Helicobacter pylori (H. pylori) is a major human pathogen associated with significant morbidity and mortality. However, after decades of efforts, treatment of H. pylori remains a challenge for physicians, as there is no universally effective regimen. Due to the rising prevalence of antimicrobial resistance, mainly to clarithromycin, efficacy of standard triple therapies has declined to unacceptably low levels in most parts of the world. Novel regimens, specifically experimented to improve the therapeutic outcome against antibiotic-resistant H. pylori strains, are now recommended as first-line empirical treatment options providing high efficacy (reportedly > 90% in intention to treat analysis) even in high clarithromycin resistance settings. These include the bismuth quadruple, concomitant, sequential and hybrid therapies. Due to the rapid development of quinolone resistance, levofloxacin-based regimens should be reserved as second-line/rescue options. Adjunct use of probiotics has been proposed in order to boost eradication rates and decrease occurrence of treatment-related side effects. Molecular testing methods are currently available for the characterization of H. pylori therapeutic susceptibility, including genotypic detection of macrolide resistance and evaluation of the cytochrome P450 2C19 status known to affect the metabolism of proton pump inhibitors. In the future, use of these techniques may allow for culture-free, non-invasive tailoring of therapy for H. pylori infection.

Nonbismuth quadruple "concomitant" therapy versus standard triple therapy, both of the duration of 10 days, for first-line H. pylori eradication: a randomized trial.

Goals: To compare the efficacy, compliance, and tolerability of a quadruple, nonbismuth-containing concomitant therapy with standard triple therapy, both of the duration of 10 days, for Helicobacter pylori eradication. Background: Eradication rates obtained with standard therapies are declining as antibiotic resistance becomes more prevalent worldwide. New first-line treatment strategies are needed. Study: Two hundred fifty-seven patients with H. pylori infection were included in the study. Patients were randomized to receive 10-day concomitant therapy comprising esomeprazole 40 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and metronidazole 500 mg, all bid, or 10-day standard triple therapy comprising of esomeprazole 40 mg, amoxicillin 1000 mg, and clarithromycin 500 mg, all bid. Cure rates were defined as a negative 13C urea breath test 8 weeks after the start of treatment. Results: Two hundred forty-six patients completed the study. The intention-to-treat cure rates were 90.5% [95% confidence interval (CI): 84.1%-95%] and 73.8% (95%CI, 65.6%-80.7%), whereas the per protocol cure rates were 93.3% (95%CI, 87.2% -97.1%) and 78.5% (95%CI, 70.3%-84.9%), respectively. The eradication rate was significantly higher in the concomitant group compared with the triple therapy group in both the intention-to-treat (P=0.0006) and per protocol (P=0.0014) populations. Adverse events were generally of mild/moderate intensity and did not interfere significantly with compliance, which was excellent for both treatment groups (96.6% and 98.5%, respectively, P=0.44). Conclusions: Performance of a 10-day conventional triple regimen is suboptimal. A 10-day concomitant regimen achieved a significantly higher eradication rate and seems to be an effective, safe, and well-tolerated treatment option for H. pylori eradication.