Endoscopic mucosal resection (EMR) versus endoscopic submucosal dissection (ESD) for resection of large distal non-pedunculated colorectal adenomas (MATILDA-trial): rationale and design of a multicenter randomized clinical trial.

BACKGROUND: Endoscopic mucosal resection (EMR) is currently the most used technique for resection of large distal colorectal polyps. However, in large lesions EMR can often only be performed in a piecemeal fashion resulting in relatively low radical (R0)-resection rates and high recurrence rates. Endoscopic submucosal dissection (ESD) is a newer procedure that is more difficult resulting in a longer procedural time, but is promising due to the high en-bloc resection rates and the very low recurrence rates. We aim to evaluate the (cost-)effectiveness of ESD against EMR on both short (i.e. 6 months) and long-term (i.e. 36 months). We hypothesize that in the short-run ESD is more time consuming resulting in higher healthcare costs, but is (cost-) effective on the long-term due to lower patients burden, a higher number of R0-resections and lower recurrence rates with less need for repeated procedures. METHODS: This is a multicenter randomized clinical trial in patients with a non-pedunculated polyp larger than 20 mm in the rectum, sigmoid, or descending colon suspected to be an adenoma by means of endoscopic assessment. Primary endpoint is recurrence rate at follow-up colonoscopy at 6 months. Secondary endpoints are R0-resection rate, perceived burden and quality of life, healthcare resources utilization and costs, surgical referral rate, complication rate and recurrence rate at 36 months. Quality-adjusted-life-year (QALY) will be estimated taking an area under the curve approach and using EQ-5D-indexes. Healthcare costs will be calculated by multiplying used healthcare services with unit prices. The cost-effectiveness of ESD against EMR will be expressed as incremental cost-effectiveness ratios (ICER) showing additional costs per recurrence free patient and as ICER showing additional costs per QALY. DISCUSSION: If this trial confirms ESD to be favorable on the long-term, the burden of extra colonoscopies and repeated procedures can be prevented for future patients. TRIAL REGISTRATION: NCT02657044 (Clinicaltrials.gov), registered January 8, 2016.

Small bowel carcinoma mimicking a relapse of Crohn's disease: a case series.

We describe three patients diagnosed and treated for presumed (relapsing) Crohn's disease, but who were subsequently diagnosed with a small bowel carcinoma. This case series underlines the necessity of performing a full work up in the diagnosis of CD and to consider small bowel carcinoma in patients with small bowel CD failing medical therapy.

[A retrospective study on the role of antibodies against soluble liver antigen (anti-SLA antibodies) and other autoantibodies in the diagnostics of autoimmune hepatitis]. / Een retrospectieve studie naar de rol van antistoffen tegen oplosbaar ('soluble') leverantigeen (anti-sLA-antistoffen) en van andere autoantistoffen bij de diagnostiek van auto-immune hepatitis.

OBJECTIVE: To determine the diagnostic value of antibodies against soluble liver antigen (anti-SLA antibodies) and a number of other antibodies for the diagnosis ofautoimmune hepatitis (AIH). DESIGN: Retrospective. METHOD: Anti-SLA, antinuclear antibodies (ANA), antibodies against smooth muscle (anti-SMA), anti-neutrophil cytoplasm antibodies (peri-nuclear pattern; pANCA) and antibodies against liver-kidney microsomal antigen type 1 (anti-LKM-1) were determined in the sera of 97 patients with AIH and 121 patients with other liver disorders including viral, drug-related and alcoholic liver disease. The sensitivity and specificity of each of the antibodies, or a combination ofantibodies, were calculated for the diagnosis 'AIH'. RESULTS: Anti-SLA antibodies were found only in AIH patients (specificity: 100%); 1 in 7 AIH patients (14%) had these antibodies and in 2% they were the only detectable antibodies. Anti-LKM-1 antibodies also showed a 100% specificity for AIH although the sensitivity was much lower (2%). Whilst the sensitivity of ANA (53%), pANCA (39%) and SMA (39%) was higher, the specificity of these antibodies for AIH was lower. 20% of AIH patients tested negative for all autoantibodies. The simultaneous presence of more than one antibody increased the probability of AIH diagnosis. CONCLUSION: When AIH is suspected, the presence of one or a combination ofanti-SLA, ANA, anti-SMA, anti-LKM-1 and pANCA antibodies is helpful for the often difficult differential diagnosis between AIH and other liver disorders. Anti-SLA antibodies are specific for AIH and appear to be a useful diagnostic parameter.

A pilot study exploring the role of glucocorticoid receptor variants in primary biliary cirrhosis and primary sclerosing cholangitis.

BACKGROUND: In primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) significant therapeutic effects of glucocorticoids have not been documented. The most important clinical problem in patients with these diseases is fatigue, which is occasionally invalidating. Abnormalities in the hypothalamo-pituitary-adrenal axis have been suggested as a cause of fatigue. Most effects of glucocorticoids are mediated by the glucocorticoid receptor (hGR alpha). Recently a causative role for a splicing variant of the glucocorticoid receptor (hGR beta) has been proposed in glucocorticoid resistance in asthma and ulcerative colitis, whereas another splicing variant (hGR P) might be associated with glucocorticoid-resistant haematological malignancies. The aims of the present pilot study were to assess abnormalities in glucocorticoid receptor expression and to relate these abnormalities to the development of fatigue and to disease activity and severity in autoimmune cholestatic liver disease. METHODS: Five fatigued and five nonfatigued patients with PBC or PSC were included, and the results were compared with healthy controls. RESULTS: The expression of hGR P was not different from controls, but hGR beta mRNA was significantly increased (p=0.02) and hGR alpha mRNA decreased (p=0.015). There were no significant differences between fatigued and nonfatigued patients. A significant negative correlation between the serum activity of alkaline phosphatase and hGR alpha and hGR P mRNA was found. CONCLUSION: Although there was no relation with fatigue, abnormalities in hGR expression appear to occur in patients with these diseases, and may play a role in its pathophysiology and the poor response to glucocorticoid treatment.

Transjugular intrahepatic portosystemic shunt (TIPS): indications and long-term patency.

BACKGROUND: Since the introduction of TIPS (the transjugular intrahepatic portosystemic shunt) into clinical practice in 1989, substantial knowledge, partially derived from controlled trials, has become available regarding technical and clinical aspects of the procedure. A number of prospective studies have assessed the long-term patency of radiological shunts, the recognized main technical weakness of the procedure. METHODS: Review of published data regarding the optimal indications and long-term patency of TIPS. RESULTS: Information on the long-term patency of TIPS is surprisingly scarce. Within 2 years of TIPS creation, re-interventions to re-establish or maintain the patency of the shunt are required in 70%-90% of patients, and in 20%-40% total occlusion develops. Limited available data suggest, however, that in about 80% of patients the shunt is patent after 3-5 years. There is consensus that TIPS is a main, second-line treatment option for variceal haemorrhage not responding to other therapies. Although widely used for treating refractory ascites, gastric variceal bleeding and Budd-Chiari syndrome, these indications require more study. A number of other potential indications remain poorly defined. CONCLUSION: TIPS is a major treatment modality to manage the complications of portal hypertension and Budd-Chiari syndrome. The available data indicate that TIPS is not only a short-term treatment option but may provide long-term portosystemic decompression. Technical improvements, e.g. the use of covered or drug-eluting stents, are essential to reduce the high rate of shunt dysfunction.