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

The ladies trial: laparoscopic peritoneal lavage or resection for purulent peritonitisA and Hartmann's procedure or resection with primary anastomosis for purulent or faecal peritonitisB in perforated diverticulitis (NTR2037)

Background: Recently, excellent results are reported on laparoscopic lavage in patients with purulent perforated diverticulitis as an alternative for sigmoidectomy and ostomy. The objective of this study is to determine whether LaparOscopic LAvage and drainage is a safe and effective treatment for patients with purulent peritonitis (LOLA-arm) and to determine the optimal resectional strategy in patients with a purulent or faecal peritonitis (DIVA-arm: perforated DIVerticulitis: sigmoidresection with or without Anastomosis). Methods/Design: In this multicentre randomised trial all patients with perforated diverticulitis are included. Upon laparoscopy, patients with purulent peritonitis are treated with laparoscopic lavage and drainage, Hartmann's procedure or sigmoidectomy with primary anastomosis in a ratio of 2:1:1 (LOLA-arm). Patients with faecal peritonitis will be randomised 1:1 between Hartmann's procedure and resection with primary anastomosis (DIVA-arm). The primary combined endpoint of the LOLA-arm is major morbidity and mortality. A sample size of 132:66:66 patients will be able to detect a difference in the primary endpoint from 25% in resectional groups compared to 10% in the laparoscopic lavage group (two sided alpha = 5%, power = 90%). Endpoint of the DIVA-arm is stoma free survival one year after initial surgery. In this arm 212 patients are needed to significantly demonstrate a difference of 30% (log rank test two sided alpha = 5% and powe

Renal function in cancer patients treated with hyperthermic isolated limb perfusion with recombinant tumor necrosis factor-α and melphalan

Hyperthermic isolated limb perfusion (HILP) with recombinant tumor necrosis factor-α (r-TNFα) and melphalan has been shown to result in a sepsis-like syndrome due to leakage of r-TNFα from the perfusion system to the systemic circulation. We have studied renal function parameters in 11 cancer patients, who underwent 12 perfusions. Three patients, perfused with melphalan only, served as controls. All patients treated with r-TNFα developed a sepsis syndrome and needed volume replacement and inotropes to remain normotensive; controls had an uneventful postoperative course. Creatinine clearance decreased transiently on the day of perfusion in both groups (mean preperfusion clearance 118 ml/min, mean post-perfusion clearance 68 ml/min, p < 0.02, n = 15). Follow-up measurements of renal plasma flow and glomerular filtration rate in 9 r-TNFα-treated patients did not suggest permanent damage. One patient became hypotensive and developed transient multiple organ dysfunction with renal failure needing hemofiltration. In r-TNFα-treated patients, but not in controls, a transient increase in clearance of β2-microglobulin (0.05 vs. 8 ml/min, p < 0.001) and urinary excretion of phosphate (12 vs. 48 mmol/l, p < 0.05) was seen, compatible with proximal tubular dysfunction. These data suggest that HILP with melphalan decreases glomerular function, whether or not r-TNFα is added to the perfusion circuit. Extension of the treatment regimen with r-TNFα may result in additional proximal tubular dysfunction. If hypotension can be avoided, this deterioration in renal function seems to be transient, with full recovery within weeks

Effects of hyperthermic isolated limb perfusion with recombinant tumor necrosis factor α and melphalan on the human fibrinolytic system

This study was undertaken to determine the effects on systemic fibrinolysis of hyperthermic isolated limb perfusion with recombinant tumor necrosis factor α (r-TNF-α) and melphalan, with or without pretreatment with recombinant IFN-γ (r-IFN-γ). Twenty patients were treated with r-TNF- α and melphalan; four patients, treated with melphalan only, served as controls. Of the twenty patients treated with both r-TNF-α and melphalan, eight received r-IFN-γ for two days before the perfusion and as a bolus into the perfusion circuit. A significant leak of r-TNF-α from lite perfusion circuit to the systemic circulation was observed in all r-TNF-α-treated patients (mean maximum TNF-α, 87,227 ng/liter versus 31 ng/liter in controls; P < 0.002). In these patients, but not in controls, there was an almost instantaneous rise in systemic tissue plasminogen activator activity (from 0.26 to 5.28 IU/ml in 90 min), causing activation of fibrinolysis. After a delay of 90 min, plasminogen activator inhibitor-1 (PAI-1) antigen rose to high levels in the r-TNF-α-treated group (mean maximum PAI-1, 1652 ng/ml versus 211 ng/ml in controls; P < 0.02), associated with a sharp decrease of tissue plasminogen activator activity and a slower decrease of plasminogen-antiplasminogen complexes (from 5.28 to 0.02 IU/ml in 2 h and from 1573 to 347 μg/liter in 22 h, respectively). No additional effect of IFN-γ pretreatment on fibrinolysis could be demonstrated. These results suggest that in isolated limb perfusion with r-TNF-α and melphalan an initial activation of systemic fibrinolysis, induced by leakage of r-TNF-α from the perfusion circuit, is set off by a subsequent inhibition of the fibrinolytic system by PAI-1. This large increase in PAI-1 could place the patient at risk for deposition of micro-thrombi in the systemic circulation

Effects of hyperthermic isolated limb perfusion with recombinant tumor necrosis factor α and melphalan on the human fibrinolytic system

This study was undertaken to determine the effects on systemic fibrinolysis of hyperthermic isolated limb perfusion with recombinant tumor necrosis factor α (r-TNF-α) and melphalan, with or without pretreatment with recombinant IFN-γ (r-IFN-γ). Twenty patients were treated with r-TNF- α and melphalan; four patients, treated with melphalan only, served as controls. Of the twenty patients treated with both r-TNF-α and melphalan, eight received r-IFN-γ for two days before the perfusion and as a bolus into the perfusion circuit. A significant leak of r-TNF-α from lite perfusion circuit to the systemic circulation was observed in all r-TNF-α-treated patients (mean maximum TNF-α, 87,227 ng/liter versus 31 ng/liter in controls; P < 0.002). In these patients, but not in controls, there was an almost instantaneous rise in systemic tissue plasminogen activator activity (from 0.26 to 5.28 IU/ml in 90 min), causing activation of fibrinolysis. After a delay of 90 min, plasminogen activator inhibitor-1 (PAI-1) antigen rose to high levels in the r-TNF-α-treated group (mean maximum PAI-1, 1652 ng/ml versus 211 ng/ml in controls; P < 0.02), associated with a sharp decrease of tissue plasminogen activator activity and a slower decrease of plasminogen-antiplasminogen complexes (from 5.28 to 0.02 IU/ml in 2 h and from 1573 to 347 μg/liter in 22 h, respectively). No additional effect of IFN-γ pretreatment on fibrinolysis could be demonstrated. These results suggest that in isolated limb perfusion with r-TNF-α and melphalan an initial activation of systemic fibrinolysis, induced by leakage of r-TNF-α from the perfusion circuit, is set off by a subsequent inhibition of the fibrinolytic system by PAI-1. This large increase in PAI-1 could place the patient at risk for deposition of micro-thrombi in the systemic circulation