Proton pump inhibitor-responsive oesophageal eosinophilia correlates with downregulation of eotaxin-3 and Th2 cytokines overexpression.

BACKGROUND: The molecular basis and effects of proton pump inhibitor (PPI) therapy on PPI-responsive oesophageal eosinophilia (PPI-REE) and eosinophilic oesophagitis (EoE) remain unknown. AIM: To compare symptom-histological and cytokine gene expression in PPI-REE and EoE patients, at baseline and after specific treatment. METHODS: In consecutive adult patients with an EoE phenotype (dysphagia/food impaction, typical endoscopic findings and > 15 eos/HPF), gene expression of eotaxin-3, IL-13, and IL-5 were determined in distal and proximal oesophagus, at baseline and after omeprazole 40 mg b.d. for 8 weeks. PPI-REE was defined by clinicohistological response. PPI nonresponders (EoE) were offered treatment with topical steroids. RESULTS: Fifty three patients were re-evaluated on PPI therapy. 23 patients (43%) had PPI-REE and 30 patients (57%) had EoE. At baseline, eotaxin-3/IL-13/IL-5 gene expression was indistinguishable between EoE and PPI-REE, excepting increased IL-5 expression in proximal oesophagus (12.54 vs. 57, P = 0.029). PPI therapy significantly decreased eotaxin-3/IL-13 in PPI-REE, at both oesophageal sites (P ≤ 0.008), and IL-5 in distal (P = 0.016), but not in proximal oesophagus. Patients with steroid-responsive EoE also showed a significant decrease in eotaxin-3/IL-5 expression at both oesophageal sites. In EoE patients, initial PPI trial significantly decreased distal oesophageal eosinophilia (63.78 to 41.79 eos/HPF, P = 0.025) and led to symptom remission in 16%, but did not influence Th2 markers. CONCLUSIONS: Baseline cytokine gene expression in PPI-REE was nearly indistinguishable from EoE. PPI therapy significantly downregulated oesophageal eotaxin-3/Th2-cytokine gene expression in PPI-REE, similarly to that seen in steroid-responsive EoE. A subset of EoE patients showed clinicohistological improvement on PPI therapy.

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

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.

[Update on medical therapy for obscure gastrointestinal hemorrhage]. / Avances en el tratamiento farmacológico de la hemorragia digestiva de origen oscuro.

The development of capsule endoscopy and double-balloon enteroscopy has increased diagnostic and therapeutic rates in obscure gastrointestinal hemorrhage, where angiodysplasia of the small bowel is the most frequent cause. Nevertheless, almost 25-40% of patients who are not candidates or do not respond to endoscopic, angiographic, or surgical management may be at high risk of rebleeding, and therefore lack a clearly effective medical therapy. The utility of hormonal therapy remains unclear and is burdened by adverse effects. Subcutaneous octreotide usually controls bleeding but does not seem adequate for maintenance therapy. Non-selective beta-blockers alone or in combination with other treatments, as in the prophylaxis of portal hypertension variceal bleeding, may be helpful. Recently, octreotide LAR, a depot formulation administered once a month intramuscularly, and oral thalidomide, a powerful inhibitor of angiogenesis, have demonstrated their effectiveness and safety for long-term therapy in anecdotal case reports and deserve further investigation.

Avances en el tratamiento farmacológico de la hemorragia digestiva de origen oscuro / Update on medical therapy for obscure gastrointestinal hemorrhage

El desarrollo de la cápsula endoscópica y la enteroscopia dedoble balón ha aumentado las tasas de diagnóstico y tratamientoen la hemorragia digestiva de origen oscuro, en la que las angiodisplasiasdel intestino delgado son la causa más frecuente. Sinembargo, el 25-40% de los pacientes, no subsidiarios o no respondedoresa la terapéutica endoscópica, angiográfica o quirúrgica,pueden tener alto riesgo de resangrado y carecen de tratamientomédico claramente eficaz. La utilidad de la terapiahormonal está cuestionada actualmente, sin olvidar los frecuentesy limitantes efectos secundarios. El octreótido suele ser eficaz enel control de la hemorragia pero no parece la terapia de mantenimientomás óptima. Los beta-bloqueantes no selectivos, de igualmanera que en la profilaxis de la hemorragia por hipertensiónportal, pueden ser útiles en combinación con otros fármacos. Recientemente,el octreotido LAR, una formulación de liberación retardadaque se administra una vez al mes por vía intramuscular, yla talidomida oral, un potente inhibidor de la angiogénesis, handemostrado su eficacia y seguridad a largo plazo en casos gravesaislado

The development of capsule endoscopy and double-balloon enteroscopy has increased diagnostic and therapeutic rates in obscuregastrointestinal hemorrhage, where angiodysplasia of thesmall bowel is the most frequent cause. Nevertheless, almost 25-40% of patients who are not candidates or do not respond to endoscopic,angiographic, or surgical management may be at highrisk of rebleeding, and therefore lack a clearly effective medicaltherapy. The utility of hormonal therapy remains unclear and isburdened by adverse effects. Subcutaneous octreotide usually controlsbleeding but does not seem adequate for mainteinance therapy.Non-selective beta-blockers alone or in combination with othertreatments, as in the prophylaxis of portal hypertensionvariceal bleeding, may be helpful. Recently, octreotide LAR, a depotformulation administered once a month intramuscularly, andoral thalidomide, a powerful inhibitor of angiogenesis, havedemonstrated their effectiveness and safety for long-term therapyin anecdotal case reports and deserve further investigation

First-line triple therapy with levofloxacin for Helicobacter pylori eradication.

BACKGROUND: At present, the efficacy of proton pump inhibitor-clarithromycin-amoxicillin regimen is relatively low. AIM: To evaluate the efficacy and tolerability of a first-line triple clarithromycin-free regimen including ranitidine bismuth citrate, levofloxacin and amoxicillin. DESIGN: Prospective study. PATIENTS: Helicobacter pylori-positive patients complaining of dyspeptic symptoms referred for gastroscopy. INTERVENTION: Levofloxacin (500 mg b.d.), amoxicillin (1 g b.d.) and ranitidine bismuth citrate (400 mg b.d.) was prescribed for 10 days. OUTCOME: Eradication was confirmed by a (13)C-urea breath test 8 weeks after therapy. Compliance with therapy was determined by questioning and the recovery of empty envelopes of medications. Incidence of adverse effects was evaluated by means of a specific questionnaire. RESULTS: Sixty-four patients were included (30% peptic ulcer, 70% functional dyspepsia). Almost all (97%) patients took all the medications correctly. Per-protocol and intention-to-treat eradication rates were 88.5% (95% CI =78-95%) and 84.4 (74-91%). Adverse effects were reported in 9.5% of the patients, mainly including diarrhoea (7.9%); none of them were severe. CONCLUSION: This new 10-day levofloxacin-based combination represents an alternative to clarithromycin-based therapy, as it meets the criteria set for regimens used as primary H. pylori treatment: effectiveness (>80%), simplicity (twice-daily dosing and excellent compliance) and safety (low incidence of adverse effects).