Laparoscopic ileocolic resection versus infliximab treatment of distal ileitis in Crohn's disease: a randomized multicenter trial (LIR!C-trial)

Contains fulltext : 69534.pdf (publisher's version ) (Open Access)BACKGROUND: With the availability of infliximab, nowadays recurrent Crohn's disease, defined as disease refractory to immunomodulatory agents that has been treated with steroids, is generally treated with infliximab. Infliximab is an effective but expensive treatment and once started it is unclear when therapy can be discontinued. Surgical resection has been the golden standard in recurrent Crohn's disease. Laparoscopic ileocolic resection proved to be safe and is characterized by a quick symptom reduction.The objective of this study is to compare infliximab treatment with laparoscopic ileocolic resection in patients with recurrent Crohn's disease of the distal ileum with respect to quality of life and costs. METHODS/DESIGN: The study is designed as a multicenter randomized clinical trial including patients with Crohn's disease located in the terminal ileum that require infliximab treatment following recent consensus statements on inflammatory bowel disease treatment: moderate to severe disease activity in patients that fail to respond to steroid therapy or immunomodulatory therapy. Patients will be randomized to receive either infliximab or undergo a laparoscopic ileocolic resection. Primary outcomes are quality of life and costs. Secondary outcomes are hospital stay, early and late morbidity, sick leave and surgical recurrence. In order to detect an effect size of 0.5 on the Inflammatory Bowel Disease Questionnaire at a 5% two sided significance level with a power of 80%, a sample size of 65 patients per treatment group can be calculated. An economic evaluation will be performed by assessing the marginal direct medical, non-medical and time costs and the costs per Quality Adjusted Life Year (QALY) will be calculated. For both treatment strategies a cost-utility ratio will be calculated. Patients will be included from December 2007. DISCUSSION: The LIR!C-trial is a randomized multicenter trial that will provide evidence whether infliximab treatment or surgery is the best treatment for recurrent distal ileitis in Crohn's disease. TRIAL REGISTRATION: Nederlands Trial Register NTR1150

Colorectal liver metastases: Surgery versus thermal ablation (COLLISION) - a phase III single-blind prospective randomized controlled trial

Background: Radiofrequency ablation (RFA) and microwave ablation (MWA) are widely accepted techniques to eliminate small unresectable colorectal liver metastases (CRLM). Although previous studies labelled thermal ablation inferior to surgical resection, the apparent selection bias when comparing patients with unresectable disease to surgical candidates, the superior safety profile, and the competitive overall survival results for the more recent reports mandate the setup of a randomized controlled trial. The objective of the COLLISION trial is to prove non-inferiority of thermal ablation compared to hepatic resection in patients with at least one resectable and ablatable CRLM and no extrahepatic disease. Methods: In this two-arm, single-blind multi-center phase-III clinical trial, six hundred and eighteen patients with at least one CRLM (≤3cm) will be included to undergo either surgical resection or thermal ablation of appointed target lesion(s) (≤3cm). Primary endpoint is OS (overall survival, intention-to-treat analysis). Main secondary endpoints are overall disease-free survival (DFS), time to progression (TTP), time to local progression (TTLP), primary and assisted technique efficacy (PTE, ATE), procedural morbidity and mortality, length of hospital stay, assessment of pain and quality of life (QoL), cost-effectiveness ratio (ICER) and quality-adjusted life years (QALY). Discussion: If thermal ablation proves to be non-inferior in treating lesions ≤3cm, a switch in treatment-method may lead to a reduction of the post-procedural morbidity and mortality, length of hospital stay and incremental costs without compromising oncological outcome for patients with CRLM. Trial registration:NCT03088150 , January 11th 2017

Jeuk en leverziekten: Krabben is te meten; jeuk niet

Pruritus is a common complication of cholestatic disorders. The pruritus of cholestasis often has an adverse impact on daily functioning and is usually difficult to treat. Empiric medications, like antihistamines and colestyramine, often are ineffective. The pathogenesis of the pruritus of cholestasis is unknown. Increased levels of bile-acids were thought to play a role, but there is a lack of scientific evidence to support this hypothesis. Recent data, however, suggest that endogenous opioids may play a role in the pathogenesis. In addition opiate antagonists may be efficacious in ameliorating this form of pruritus

Adenoviral serotypes in gene therapy for esophageal carcinoma

PURPOSE: Adenoviral gene therapy could potentially play a role in the treatment of esophageal cancer and Barrett's esophagus. The adenoviruses can be categorized in different serotypes. The goal of the present study was to investigate the transduction efficacy of different adenoviral serotypes in different models of esophageal cancer and Barrett's esophagus. METHODS: Chimeras of the adenoviral serotype 5 backbone and fibers of serotypes 5, 16, 35, 40, and 50 were constructed with PCR technology. For esophageal cancer, cell lines were used originating from with adenocarcinoma and squamous cell carcinoma, respectively. Differentiating Caco-2 cells were used as an in vitro model for Barrett's esophagus. GFP was used as a reporter gene and transduction efficacy was assessed by flow cytometry. RESULTS: Overall transduction was rather efficient in the cancer cell lines. Especially serotype 16 and 50 exhibited an improved transduction compared with the other serotypes. In the Caco-2 cell lines, we observed a decreased transduction upon differentiation of the cells. All serotypes had a very limited transduction and no serotype had an additional value in this setting. CONCLUSIONS: Some serotypes could have an additional value in the development of gene therapy for esophageal cancer. Especially serotype 16 and 50 exhibited an improved transduction in esophageal cancer cells compared with the native serotype 5. In the setting of Barrett's esophagus, none of the serotypes had an improved potency as in differentiated intestinal cells all serotypes had a very limited transductio

Gene therapy for barrett's esophagus: adenoviral gene transfer in different intestinal models

Adenoviral gene therapy could potentially be used for treatment of patients with a Barrett's esophagus. In order to study the feasibility of this approach it is important to study adenoviral intestinal transduction both in vitro and in vivo. In the present study, we used differentiating Caco-2 cells, closed intestinal loops and a Barrett's esophagus rat model to test transduction of adenoviruses expressing green fluorescent protein. We observed a decreased adenoviral transduction from 18.6 to 2.3% in undifferentiated and differentiated Caco-2 cells, respectively. This could be improved by the use of the mucolytic agent N-acetylcysteine (NAC) and the polycation diethylaminoethyl-dextran (DEAE-dextran), which improved transduction in differentiated cells five- and ten-fold, respectively. Also an RGD-retargeted adenovirus showed an improved transduction in differentiated cells. In closed intestinal loops adenoviral transduction was limited and the use of NAC and DEAE-dextran or RGD targeting had little effect. The Barrett's esophagus rat model consisted of an esophagojejunostomy, which results in a Barrett's esophagus and esophageal tumors within 6 months. Adenoviral transduction in this model was limited and mainly localized in the basal layer of normal esophagus and stromal tissue of a Barrett's segment. We conclude that although the adenovirus shows promising results in vitro, the current adenoviral vectors are probably not suitable for patients with Barrett's esophagu

The presence and mucin histochemistry of cardiac type mucosa at the esophagogastric junction

OBJECTIVES: Traditionally, the gastric cardia has been described as a native part of the stomach connecting to the esophagus. In recent literature, however, it is suggested that the cardia is an acquired lesion that develops due to gastroesophageal reflux disease. As a contribution to this debate, we evaluated the presence of cardiac mucosa at the esophagogastric junction (EGJ) in a random group of patients who presented at our endoscopy unit. METHODS: In 253 unselected patients, biopsies were taken from the EGJ. In order to prevent sampling error, we selected only those EGJ biopsies in which the squamocolumnar junction (SCJ) was present in the histological biopsy material. Fifty-five patients were excluded since the SCJ was located proximal to the EGJ in the esophagus. The type of columnar mucosa immediately distal to the SCJ, and its mucin histochemistry, were assessed. The columnar mucosa was categorized as purely cardiac, oxyntocardiac, or fundic mucosa. RESULTS: In 63 of the 198 patients, the SCJ was actually present in the EGJ biopsies. Purely cardiac mucosa was present in 39 (62%) biopsies and oxyntocardiac mucosa was present in 24 (38%) biopsies. Fundic mucosa was not seen directly adjacent to squamous epithelium. Acid mucins were present in 23 (37%) patients and they correlated with histological esophagitis and presence of H. pylori in the cardia. CONCLUSIONS: Cardiac mucosa was uniformly present adjacent to the squamous epithelium at the EGJ. This argues against the hypothesis that the gastric cardia is an acquired metaplastic lesion. The presence of acid mucins was frequently observed and could be a pathological condition as it was associated with histological esophagitis and the presence of H. pylori in the cardi

Loss of heterozygosity and immunohistochemistry of adenocarcinomas of the esophagus and gastric cardia

PURPOSE: Adenocarcinomas of the distal esophagus and gastric cardia are two tumors that have many features in common. They have similar prognoses, treatment modalities, and patterns of dissemination. The etiology is different, with gastroesophageal reflux disease playing a major role for esophageal adenocarcinoma, in contrast to adenocarcinoma of the gastric cardia. In the present study, we investigated several genetic and immunohistochemical features of adenocarcinomas of the distal esophagus and gastric cardia. EXPERIMENTAL DESIGN: Sixty-two resection specimens of either adenocarcinoma of the esophagus or adenocarcinoma of the gastric cardia were carefully selected. The genetic analysis included loss of heterozygosity of several tumor suppressor genes known to be involved in esophagogastric carcinogenesis. Immunohistochemical studies included the analysis of p53, c-Met, c-erbB-2, beta-catenin, and cyclooxygenase-2. In addition, a mutation analysis of the Tcf1 gene was done by direct sequencing. RESULTS: Patients with cardiac carcinoma had a significantly worse tumor stage and poorer differentiation on histology. Loss of heterozygosity analysis did not reveal significant differences between esophageal adenocarcinoma and cardiac adenocarcinoma. Immunohistochemical analysis revealed significantly more nuclear accumulation of beta-catenin and overexpression of cyclooxygenase-2 in patients with esophageal adenocarcinoma, compared with patients with cardiac carcinoma. No mutation was found in the Tcf1 gene in either tumor type. CONCLUSIONS: Although adenocarcinomas of the distal esophagus and gastric cardia have many features in common, we have found some evidence that they might form two different entitie