Preoperative Predictors of Neoplasia in Patients Undergoing Small Bowel Resection for Complicated Crohn's Disease: A Multicentre Case-Control Study.

Crohn's disease (CD) is associated with an increased risk of small bowel neoplasia (SBN). We aimed to assess preoperative predictors of SBN in CD patients. We conducted a retrospective case-control study including CD patients who underwent surgery: cases were diagnosed with SBN on histopathological analysis and controls had no neoplasia. Preoperative cross-sectional imaging was reviewed by a panel of blinded expert radiologists. Fifty cases were matched to one hundred and fifty consecutive controls. In multivariable analysis, predictors of SBN were age ≥ 50 years (OR = 28, 95% CI = 5.05-206), median CD duration ≥ 17.5 years (OR = 4.25, 95% CI = 1.33-14.3), and surgery for stricture (OR = 5.84, 95% CI = 1.27-35.4). The predictors of small bowel adenocarcinoma were age ≥ 50 years (OR = 5.14, 95% CI = 2.12-12.7), CD duration ≥ 15 years (OR = 5.65, 95% CI = 2.33-14.3), and digestive wall thickening > 8 mm (OR = 3.79, 95% CI = 1.45-11.3). A predictive score based on the aforementioned factors was constructed. Almost 73.7% of patients with a high score had SBA. Old age, long small bowel CD duration, and stricture predicted the presence of SBN, particularly adenocarcinoma when patients have digestive wall thickening > 8 mm on preoperative imaging.

Phase III randomized trial comparing systemic versus intra-arterial oxaliplatin, combined with LV5FU2 +/- irinotecan and a targeted therapy, in the first-line treatment of metastatic colorectal cancer restricted to the liver (OSCAR): PRODIGE 49.

INTRODUCTION: In patients with unresectable liver metastases from colorectal cancer (CRCLM), systemic doublet or triplet chemotherapy and targeted therapy is considered a standard first-line treatment. Hepatic arterial infusion of oxaliplatin (HAI-ox) generates a high response rate, but this still needs to be confirmed in a randomized trial. We incorporated HAI-ox in doublet or triplet + targeted therapy to validate its efficacy. AIM: The OSCAR study is an ongoing randomized phase III trial comparing FOLFOX + targeted therapy according to RAS status, or FOLFOXIRI + bevacizumab in patients eligible for triplet therapy, with the same regimen but with HAI-ox instead of IV-ox as the first-line treatment for CRCLM. MATERIALS AND METHODS: Main eligibility criteria are colorectal cancer, unresectable liver metastasis, no extra-hepatic metastases except pulmonary nodules if ≤3 and <10 mm, ECOG performance status 0 or 1. ENDPOINT: The primary endpoint is progression-free survival (PFS). A difference of 4 months for the median PFS in favor of HAI-ox is expected (HR = 0.73). Secondary endpoints include overall survival, overall response rate, secondary liver resection, safety, and quality of life. CONCLUSION: This study is planned to include 348 patients to demonstrate the superiority of HAI-ox over systemic oxaliplatin in first-line CRCLM treatment (NCT02885753).

Comparative efficacy and safety of vedolizumab and infliximab in ulcerative colitis after failure of a first subcutaneous anti-TNF agent: a multicentre cohort study.

BACKGROUND: Few data exist to help select a second biologic agent in patients with refractory ulcerative colitis (UC). AIM: To compare the efficacy of infliximab (IFX) and vedolizumab (VDZ) in UC patients who failed a first subcutaneous anti-tumor necrosing factor (TNF) agent. METHODS: Consecutive UC patients from 12 French centres starting IFX or VDZ after at least one injection of adalimumab or golimumab have been included in a retrospective study. Outcomes were clinical remission at week 14, survival without treatment discontinuation and survival without UC-related event. RESULTS: Among the 225 patients included, clinical remission at week 14 was achieved in 40/154 (26%) patients treated with IFX and in 35/71 (49%) treated with VDZ (P = 0.001). After a propensity score matching analysis, this difference remained significant (odds ratio: 1.67; 95% confidence interval: 1.08-2.56; P = 0.02). With a median follow-up of 117 weeks, survival rates without treatment discontinuation at years 1 and 3 were 50% and 29% with IFX, and 80% and 55% with VDZ, respectively (P < 0.001). Regarding survival without UC-related event, they were 49% and 27% with IFX, and 74% and 52% with VDZ (P < 0.01). CONCLUSION: After failure of a first subcutaneous anti-TNF agent, UC patients were more likely to achieve clinical remission with VDZ than those treated with IFX. Although due to prescription habits patients in the IFX group had a significantly more severe disease, these differences remained after adjustments and subgroup analyses. Such results have to be confirmed prospectively and warrant dedicated head-to-head trials.

[Proton pump inhibitors in gastro-oesophageal reflux disease: what is the further step?]. / Reflux gastro-œsophagien : comment progresser au-delà des inhibiteurs de la pompe à protons ?

Optimisation of proton pump inhibitors use may improve reflux symptoms in 20-25% of the patients. Pathological gastro-oesophageal reflux should be documented in a patient with refractory reflux symptoms using upper endoscopy and/or pH testing. While on proton pump inhibitors twice daily, persistent symptoms are not related to gastro-oesophageal refluxdisease(GERD) in 50% of the patients. The new anti-reflux compounds have yet a limited efficacy and side effects that currently limit their development.

Novel therapeutics for gastro-esophageal reflux symptoms.

Approximately 20-30% of patients with gastro-esophageal reflux symptoms report inadequate symptom relief while on proton-pump inhibitor therapy. The mechanisms involved are failure of the antireflux barrier (transient lower esophageal sphincter relaxations), high proximal extent of the refluxate, esophageal hypersensitivity and impaired mucosal integrity. Persisting acid or nonacid reflux can be demonstrated in 40-50% of cases, suggesting that there is room for antireflux therapy in these patients. New antireflux compounds have been shown to decrease the occurrence of transient lower esophageal sphincter relaxations. The most promising classes of compounds are GABA type B agonists and metabotropic glutamate receptor 5 antagonists, which can reduce both reflux episodes and symptoms, but the development of these compounds has been abandoned for either safety issues or lack of efficacy. Esophageal hypersensitivity and impaired mucosal integrity may prove to be relevant therapeutic targets in the future.

Functional heartburn: definition and management strategies.

Functional heartburn (FH) is a functional gastro-intestinal disorder characterized by symptoms of heartburn not related to gastro-esophageal reflux. The absence of evidence of reflux-related symptoms relies on absence of esophagitis at endoscopy (including biopsies to exclude eosinophilic esophagitis), a normal esophageal acid exposure during esophageal pH-monitoring together with a negative symptom-reflux association analysis and an unsatisfactory response to proton pump inhibitor therapy. Addition of impedance measurement to pH-monitoring is likely to increase the number of patients with recognized reflux-related symptoms. The pathophysiology of functional heartburn remains largely unknown but involves disturbed esophageal perception and psychological factors such as depression, anxiety and somatization. The treatment of FH remains largely empirical and an individual approach is therefore recommended. The clinician should provide reassurance and refrain from performing too many invasive tests or therapeutic procedures. The use of pain modulators is recommended by most experts despite the lack of appropriate clinical trials to support it.

Clinical, but not oesophageal pH-impedance, profiles predict response to proton pump inhibitors in gastro-oesophageal reflux disease.

OBJECTIVE: Approximately 30% of patients with gastro-oesophageal reflux disease (GORD) do not achieve adequate symptom control with proton pump inhibitors (PPIs). The aim of this study was to determine whether any symptom profile or reflux pattern was associated with refractoriness to PPI therapy. DESIGN: Patients with typical GORD symptoms (heartburn and/or regurgitation) were included and had 24 h pH-impedance monitoring off therapy. Patients were considered to be responders if they had fewer than 2 days of mild symptoms per week while receiving a standard or double dose of PPI treatment for at least 4 weeks. Both clinical and reflux parameters were taken into account for multivariate analysis (logistic regression). RESULTS: One hundred patients were included (median age 50 years, 42 male), 43 responders and 57 non-responders. Overall, multivariate analysis showed that the factors associated with the absence of response were absence of oesophagitis (p=0.050), body mass index (BMI) ≤25 kg/m(2) (p=0.002) and functional dyspepsia (FD) (p=0.001). In patients who reported symptoms during the recording (n=85), the factors associated with PPI failure were BMI ≤25 kg/m(2) (p=0.004), FD (p=0.009) and irritable bowel syndrome (p=0.045). In patients with documented GORD (n=67), the factors associated with PPI failure were absence of oesophagitis (p=0.040), FD (p=0.003), irritable bowel syndrome (p=0.012) and BMI ≤25 kg/m(2) (p=0.029). CONCLUSION: No reflux pattern demonstrated by 24 h pH-impedance monitoring is associated with response to PPIs in patients with GORD symptoms. In contrast, absence of oesophagitis, presence of functional digestive disorders and BMI ≤25 kg/m(2) are strongly associated with PPI failure.

[Standards, Options and Recommendations 2005 for a good practice in enteral nutrition in oncology (summary report.)]. / Recommandations pour la pratique clinique: Standards, Options et Recommandations 2005. Bonnes pratiques pour la prise en charge diététique en cancérologie: la nutrition entérale (rapport abrégé). Validation du rapport original: avril 2005.

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, which started in 1993, is a collaboration between the French Federation of Cancer Centers (FNCLCC), the 20 French Regional Cancer Centers, and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. OBJECTIVE: To develop good practice guidelines for a good practice of enteral nutrition in oncology, in collaboration with three French learned societies involved in this area. METHOD: The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts who define the CPGs according to the definitions of the Standards, Options and Recommendations project. Once the guideline has been defined, the document is submitted for review by independent reviewers. RESULTS: The good practices suggested in the document approach seven topics: indications and counter-indications, conditions of the installation of the enteral nutrition, monitoring, prevention of complications, education of the patient, specificities of enteral nutrition in children and at home. In the setting of enteral nutrition, feeding tubes, type of insertion, enteral nutrition products, material and techniques of administration are described as well as the criteria permitting their selection.