Showing papers by "Javier P. Gisbert published in 2010"

Sequential therapy for Helicobacter pylori eradication: a critical review.

Abstract: Background Alternative treatment regimens for standard triple therapy are urgently needed. Aim To critically review the evidence on the role of "sequential" regimen for the treatment of Helicobacter pylori infection. Methods Bibliographical searches were performed in MEDLINE and international congresses. Results Several pooled-data analyses and meta-analyses have demonstrated that sequential regimen is more effective than standard triple therapy. Sequential therapy is not affected by bacterial (CagA status, infection density) and host factors (underlying disease, smoking). Clarithromycin resistance seems to be the only factor reducing their efficacy. However, even in these patients, an acceptable >75% eradication rate can be achieved. Unfortunately, almost all the studies have been performed in Italy. Whether it is necessary to provide the drugs sequentially or if the 4 components of sequential therapy can be given concurrently is unclear. Nonbismuth quadruple therapy seems to be an effective and safe alternative to triple therapy and is less complex than sequential therapy. Conclusions Sequential therapy is a novel promising treatment approach that deserves consideration as a treatment strategy for H. pylori infection. However, further robust assessment across a much broader range of patients is required before sequential therapy could supplant existing treatment regimens and be generally recommended in clinical practice.

Liver dysfunction related to hepatitis B and C in patients with inflammatory bowel disease treated with immunosuppressive therapy

Abstract: Background There is no information about the frequency of liver dysfunction in patients with inflammatory bowel disease (IBD) treated with immunosuppressants and infected with hepatitis B (HBV) and/or C virus (HCV). Aim To assess the influence of immunosuppressants on the course of HBV and HCV infection in IBD. Methods Patients with IBD with HBV and/or HCV infection from 19 Spanish hospitals were included. Clinical records were reviewed for the type of immunosuppressant used, treatment duration, liver function tests and viral markers before, during and after each immunosuppressant. Logistic and Cox regression analysis were used to identify predictors of outcome. Results 162 patients were included; 104 had HBV markers (25 HBsAg positive) and 74 had HCV markers (51 HCV-RNA positive), and 16 patients had markers of both infections. Liver dysfunction was observed in 9 of 25 HBsAg positive patients (36%), 6 of whom developed hepatic failure. Liver dysfunction in HCV was observed in 8 of 51 HCV-RNA positive patients (15.7%), and only one developed hepatic failure. The frequency and severity of liver dysfunction was significantly higher in HBV-infected patients than in HCV-infected patients (p=0.045 and p=0.049, respectively). Treatment with ≥2 immunosuppressants was an independent predictor of HBV reactivation (OR 8.75; 95% CI 1.16 to 65.66). The majority of patients without reactivation received only one immunosuppressant for a short period and/or prophylactic antiviral treatment. No definite HBV reactivations were found in anti-HBc positive patients lacking HBsAg. Conclusion Liver dysfunction in patients with IBD treated with immunosuppressants is more frequent and severe in those with HBV than in HCV carriers and is associated with combined immunosuppression.

Clinical trial: clarithromycin vs. levofloxacin in first‐line triple and sequential regimens for Helicobacter pylori eradication

Abstract: Aliment Pharmacol Ther 31, 1077–1084 Summary Background Helicobacter pylori eradication rates with standard triple therapy have declined to unacceptable levels. Aim To compare clarithromycin and levofloxacin in triple and sequential first-line regimens. Methods A total of 460 patients were randomized into four 10-day therapeutic schemes (115 patients per group): (i) standard OCA, omeprazole, clarithromycin and amoxicillin; (ii) triple OLA, omeprazole, levofloxacin and amoxicillin; (iii) sequential OACM, omeprazole plus amoxicillin for 5 days, followed by omeprazole plus clarithromycin plus metronidazole for 5 days; and (iv) modified sequential OALM, using levofloxacin instead of clarithromycin. Eradication was confirmed by 13C-urea breath test. Adverse effects and compliance were assessed by a questionnaire. Results Per protocol cure rates were: OCA (66%; 95% CI: 57–74%), OLA (82.6%; 75–89%), OACM (80.8%; 73–88%) and OALM (85.2%; 78–91%). Intention-to-treat cure rates were: OCA (64%; 55–73%), OLA (80.8%; 73–88%), OACM (76.5%; 69–85%) and OALM (82.5%; 75–89%). Eradication rates were lower with OCA than with all the other regimens (P < 0.05). No differences in compliance or adverse effects were demonstrated among treatments. Conclusions Levofloxacin-based and sequential therapy are superior to standard triple scheme as first-line regimens in a setting with high clarithromycin resistance. However, all of these therapies still have a 20% failure rate.

Safety of immunomodulators and biologics for the treatment of inflammatory bowel disease during pregnancy and breast-feeding

Abstract: The aim of this article is to critically review available data regarding the safety of immunomodulators and biological therapies during pregnancy and breast-feeding in women with inflammatory bowel disease. Methotrexate and thalidomide can cause congenital anomalies and are contraindicated during pregnancy (and breast-feeding). Although thiopurines have a Food and Drug Administration (FDA) rating D, available data suggest that these drugs are safe and well tolerated during pregnancy. Although traditionally women receiving azathioprine or mercaptopurine have been discouraged from breast-feeding because of theoretical potential risks, it seems that these drugs may be safe in this scenario. Treatment with cyclosporine for steroid-refractory ulcerative colitis (UC) during pregnancy can be considered safe and effective, and the use of this drug should be considered in cases of severe UC as a means of avoiding urgent surgery. Breast-feeding is contraindicated for patients receiving cyclosporine. Biological therapies appear to be safe in pregnancy, as no increased risk of malformations has been demonstrated. Therefore, the limited clinical results available suggest that the benefits of infliximab and adalimumab in attaining response and maintaining remission in pregnant patients might outweigh the theoretical risks of drug exposure to the fetus. Stopping therapy in the third trimester may be considered, as it seems that transplacental transfer of infliximab is low prior to this. Certolizumab differs from infliximab and adalimumab in that it is a Fab fragment of an antitumor necrosis factor alpha monoclonal antibody, and therefore it may not be necessary to stop certolizumab in the third trimester. The use of infliximab is probably compatible with breast-feeding.

Treatment of Helicobacter pylori infection 2010.

Abstract: It is accepted that the success of Helicobacter pylori eradication treatment using standard triple therapy is declining. Resistance, particularly to clarithromycin, has been shown in numerous countries to be rising to a level where the use of standard triple therapy in its current form may no longer be justified. The two major factors influencing resistance are prior exposure to the antibiotic and compliance with therapy. Regimes based on bismuth and levofloxacin, which had previously been mainly second-line options, are now emerging as superior first-line options. Trials of sequential and concomitant therapies are also showing the usefulness of these treatments in different populations. Options for third and subsequent line therapies include furazolidone and rifabutin-based regimes. Susceptibility testing should be performed to maintain accurate data on resistance levels, and has also clinical utility in difficult to eradicate cases. None of these, however, will be successful unless compliance is improved upon. If compliance is assured and eradication confirmation pursued, it has been repeatedly illustrated that near full eradication is achievable.

Primer consenso español sobre el tratamiento de la hemorragia digestiva por úlcera péptica

Abstract: Angel Lanas , Xavier Calvet b,c, , Faust Feu , Julio Ponce , Javier P. Gisbert , Alan Barkun g y en representacion del Consenso sobre Hemorragia Digestiva por Ulcera Peptica a Servicio de Aparato Digestivo, Hospital Clinico Universitario, Zaragoza, Espana b Centro de Investigacion Biomedica en Red de enfermedades hepaticas y digestivas (CIBERehd), Instituto de Salud Carlos III c Servicio de Patologia Digestiva, Hospital Parc Tauli, Sabadell, Barcelona, Espana d Servicio de Gastroenterologia, Hospital Clinic, Barcelona, Espana e Servicio de Medicina Digestiva, Hospital La Fe, Valencia, Espana f Servicio de Aparato Digestivo, Hospital de La Princesa, Madrid, Espana g Division of Gastroenterology, Montreal General Hospital Site, The McGill University Health Centre, Montreal, Canada

The sequential therapy regimen for Helicobacter pylori eradication

Abstract: Importance of the field: Standard triple therapy (STT) is the most used treatment for Helicobater pylori infection. The prevalence of antibiotic resistance has increased substantially in recent years and there has been a corresponding decrease in efficacy.Areas covered in this review: Bibliographical searches were performed in MEDLINE and international congresses up to 2009 for ‘Helicobacter pylori’ AND ‘sequential regimen/therapy’.What the reader will gain: Several meta-analyses have demonstrated that sequential therapy (SQT) is more effective than STT. SQT is not affected by bacterial and host factors that have, until now, predicted the outcome of STT. Primary clarithromycin resistance is the only factor reducing the efficacy of SQT; however, even in these patients an acceptable > 75% eradication can be achieved. So far, almost all the studies have been performed in Italy. The advantages of SQT over STT should be confirmed in different countries. Whether it is necessary to provide the drugs sequentially...

Mercaptopurine rescue after azathioprine-induced liver injury in inflammatory bowel disease.

Abstract: Summary Background Azathioprine (AZA) liver toxicity arises in approximately 3% of inflammatory bowel disease patients and may result in treatment discontinuation Aim To describe the tolerance to mercaptopurine (MP) in patients with previous AZA-related liver injury Methods Retrospective description of 31 patients (14 Crohn’s, 17 ulcerative colitis), in which AZA therapy was interrupted because of liver injury, with MP started as alternative therapy Results Mean AZA dose was 22 ± 04 mg·kg/day Median (interquartile range) of AZA exposure when liver injury was detected was 2 months (1–52) The type of AZA-related injury was cytolitic in 32%, cholestatic in 39% and mixed in 29% After a median of 25 months (07–52), the therapy was switched to MP at a mean dose of 13 ± 02 mg·kg/day Median of follow-up of MP therapy was 32 months (8–54) In 871% of patients (95%CI: 70–96%), MP was tolerated without further liver injury; of these, 774% tolerated full MP doses and 97% tolerated lower doses In a further cohort of 129% of patients, (95%CI: 3–29%), liver injury reappeared (two cholestasis, two mixed), 1–3 months after the onset of MP exposure Conclusion The administration of MP is a good alternative in patients with AZA-related liver injury, before thiopurines are definitely discarded

Clarithromycin or levofloxacin in the sequential therapy for H. pylori eradication? authors’ reply

Abstract: Clarithromycin or levofloxacin in the sequential therapy for H. pylori eradication? authors’ reply SIRS, We thank Zullo et al. for their five useful observations on our article. However, we believe there has been a misunderstanding as no result from our study suggests that levofloxacin-based regimens achieved higher eradication rates than clarithromycin sequential therapy. 1 The conclusions in the abstract state that clarithromycin sequential and both levofloxacin regimens were significantly better than triple standard therapy, regardless of their suboptimal efficacy. 2 The figures in the results section do not show differences between clarithromycin and levofloxacin regimens. 3 In the discussion, clarithromycin sequential therapy is defined as suboptimal [intention-to-treat (ITT) eradication rate <80%], whereas levofloxacin-based regimens are defined as adequate, but poor (ITT eradication rate 80–85%), in accordance with current standards. According to this definition, one cannot declare that one is better than the other. 4 We also discuss that the fact that cure rates obtained with levofloxacin regimens in Spain are the worst reported in literature (72–82%) is possibly related to a higher levofloxacin resistance than the generally reported (1.8–6%). 5 As such, levofloxacin-based regimens are finally recommended to be saved for second and third-line therapies, owing to their relatively poor efficacy and higher cost. Likewise, we would like to reflect on data published in abstract form of an interesting study from Italy, the same setting as that in the study of Zullo et al., which will be soon presented during 2010 Digestive Diseases Week. This study compares 10-day sequential therapy (proton pump inhibitor, amoxicillin and tinidazole) using clarithromycin (CLA-ST), levofloxacin 250 mg b.d. (LEV250-ST) and levofloxacin 500 mg b.d. (LEVO500-ST) with a priori similar antibiotic resistance rate than in Spain (clarithromycin 20%, levofloxacin 3%). ITT cure rates for LEV500-ST (97%) and LEV250-ST (95%) were significantly higher (P < 0.001) than for CLA-ST (80%). Thus, contrary to the line of arguREFERENCES

Influence of thymidylate synthase DNA polymorphisms and gender on the clinical evolution of patients with advanced colorectal cancer

Abstract: Experimental evidence has revealed that several thymidylate synthase (TS) DNA polymorphisms modulate gene expression, which, in turn is known to be down-regulated by oestrogen receptor subtypes. Consequently, this process might be influenced by female hormones. Based on these data, we investigated whether patient's gender and TS polymorphism exert an interactive effect on the clinical evolution of patients with advanced colorectal cancer (CRC) subjected to 5 fluorouracil (5FU)-based adjuvant chemotherapy. A retrospective study was carried out on paraffin-embedded sections from 81 CRC patients. A variable tandem repeat (VNTR) of 28 bp, a G/C single nucleotide polymorphism (SNP), and a deletion of 6 bp (ins1494del 6 bp) were studied. Genotyping methods were polymerase chain reaction (PCR) for VNTR, and PCR followed by restriction length fragment polymorphism (PCR-RFLP) for SNP and ins1494del 6 bp. The effect of TS genotype and gender on overall and progression-free survival was assessed in univariate and multivariate (Cox regression model) tests. In male patients, the study of combined TS genotypes showed that G&6+/6+ was an adverse marker for overall (P=0.04; median: not reached) and progression-free survival (P=0.03; median: 12 months, 95% CI: 0-32.4). In the multivariate analysis, the concurrence of G&6+/6+ combination and male patients resulted in a 5.5-fold increased risk of relapse or disease progression (95% CI: 1-32.1; likelihood test P=0.004; interaction P=0.06). TS genotype did not affect survival among women. The present study supports that the effect of TS polymorphisms on the clinical evolution of advanced CRC patients is significantly influenced by gender.

Intravenous iron in digestive diseases: a clinical (re)view.

Abstract: Intravenous iron has been considered dangerous by many clinicians. In the last two decades, considerable experience has been gained with new formulations in different clinical settings. Data from clinical trials, observational studies, and postmarketing surveillance studies demonstrate that intravenous iron is safe and effective to treat iron deficiency and iron deficiency anaemia. Iron deficiency is particularly common in many digestive diseases: oral iron often fails while transfusions are not without considerable risks. In particular, in inflammatory bowel diseases, there is enough evidence to recommend intravenous iron in moderate-to-severe iron deficiency anaemia, in intolerance to oral iron, and in patients needing quick recovery (pre-operative setting). New formulations make treatment even easier and more convenient. Recent guidelines are available for inflammatory bowel diseases, and new guidelines in acute and chronic gastrointestinal bleeding are needed.

Prospective evaluation of a clinical guideline recommending early patients discharge in bleeding peptic ulcer.

Abstract: Background and Aim: To validate an early discharge policy in patients admitted with upper gastrointestinal bleeding (UGIB) due to ulcers. Methods: Patients with gastroduodenal ulcer or erosive gastritis/duodenitis were included in a previous study aiming to develop a practice guideline for early discharge of patients with UGIB. Variables associated with unfavorable evolution were analyzed in order to identify patients with low-risk of re-bleeding. After that, a one-year prospective analysis of all UGIB episodes was carried out. Results: A total of 341 patients were identified in the retrospective study. Variables associated with unfavorable evolution were: systolic blood pressure ≤ 100 mmHg, heart rate ≥ 100 bpm, and a Forrest endoscopic classification of severe. 10% of patients were immediately discharged; however, if predictive variables obtained in the multivariate analysis had been used, hospitalization could have been prevented in 34% of patients. A total of 77 patients were included in the prospective analysis. Although only 19.5% of patients were immediately discharged without complications, 29 patients (37.7%) were theoretically suitable for early discharge. Conclusions: Patients with UGIB who have clean-based ulcers and are stable on admission can be safely discharged immediately after endoscopy. Implementation of the clinical practice guideline safely reduced hospital admission for those patients.

Usefulness of manometry to select patients with anal fissure for controlled anal dilatation

Abstract: Aim: To evaluate the use of anorectal manometry to select pa tients for controlled anal dilatation. Methodology: A prospective study was performed using anorectal manometry on all patients with chronic anal fissure who did not have a good response to conservative treatment. Those with increased anal resting pressure were treated with controlled anal dilatation using a two valved anuscope. A second anorectal manometry was indicated after controlled anal dilatation. Results: 19 patients without anorectal pathology (Healthy Control Group) and 57 patients with chronic anal fissure were in cluded in this study. Controlled anal dilatation was performed on 27 patients, maximum resting pressure 122 ± 19 mmHg. In the controlled anal dilatation group the healing rate was 92.5%, mean maximum resting pressure post-controlled anal dilatation was 91 ± 30 mmHg. We found one case of transitory anal incontinence (3.7%). None of the patients had anal incontinence at 18 months of the follow-up. In the remaining 30 patients non selected for controlled anal dilatation (chronic anal fissure control group), a proportion of 53.3% recurrences were registered after conserva tive treatment. Conclusions: Anal healing of chronic anal fissure and a sig nificant decrease in maximum resting pressure recorded by manometry confirms the success of this procedure. The mano metric evaluation of the maximum resting pressure is useful in the selection of chronic anal fissure patients for controlled anal dilata tion. The efficacy of dilatation to treat chronic anal fissure in pa tients with raised anal sphincter pressure was high and complica tions were rare.

Usefulness of salicylate and thiopurine coprescription in steroid-dependent ulcerative colitis and withdrawal strategies:

Abstract: 5-aminosalicylic acid (5-ASA) and thiopurines (azathioprine and mercaptopurine) are the most common drugs used as a maintenance treatment for ulcerative colitis. A considerable proportion of these patients develop corticosteroid dependency, and thiopurines are the standard treatment in this scenario. Dual prescriptions of both thiopurines and 5-ASA are common practice in steroid-dependent ulcerative colitis, in an attempt to optimize the efficacy of therapy. On the one hand, the potential protective role of 5-ASA against colorectal cancer argues in favour of prescription of both medications. The possible synergism between the two drugs, because of the inhibition of thiopurine methyltransferase (TPMT) enzyme activity by 5-ASA, has been postulated as another justification for dual prescription. However, existing evidence does not support that this combined strategy is superior to monotherapy with thiopurines. On the other hand, in patients showing prolonged disease remission, the possibility of discontinuing maintenance treatment can be considered on an individualized basis. The high frequency of relapses after thiopurine withdrawal should always be taken into account, but the potential adverse effects of the medication also need to be considered. A properly indicated treatment with thiopurines may need to be continued for life in many patients.

Can systemic cytokines predict relapse of inflammatory bowel disease

Abstract: Background/aims To determine the value of systemic cytokines as predictors of relapse in inflammatory bowel disease (IBD). Methodology A prospective study with 135 patients in clinical remission for at least 3 months. At enrollment, a venous blood was drawn in order to measure, by an ELISA test, the following cytokines: TNFalpha, TNFalpha-R1 and R2, IL-16, IL-1beta, IL 2, IL-R2, IL-6, IL-10, and IFNgamma. All patients were followed-up for one year. Result Sixty-six patients had Crohn's disease (CD) and 69 had ulcerative colitis (UC). Thirty-nine (30%) had a relapse. Forty-four percent were receiving immunomodulatory therapy. No differences were found regarding detection and baseline concentration of the various cytokines between patients with CD and UC, or between patients with or without ongoing use of immunomodulators. The detection and concentration levels of cytokines were not associated with the risk of relapse of IBD. Conclusions Systemic cytokines are of little value to predict IBD relapse.

Otitis externa maligna. Nuestra experiencia

Abstract: Resumen La otitis externa maligna es una infeccion severa cuyo diagnostico y tratamiento continua suponiendo un reto para el clinico. El objeto de este estudio es demostrar la importancia de un analisis clinico detallado y aportar una puesta al dia de las herramientas diagnosticas y terapeuticas actualmente disponibles.