Bernhard Werner Marcel Spanier

Infected necrotising pancreatitis is a potentially lethal disease that nearly always requires intervention. Traditionally, primary open necrosectomy has been the treatment of choice. In recent years, the surgical step-up approach, consisting of percutaneous catheter drainage followed, if necessary, by (minimally invasive) surgical necrosectomy has become the standard of care. A promising minimally invasive alternative is the endoscopic transluminal step-up approach. This approach consists of endoscopic transluminal drainage followed, if necessary, by endoscopic transluminal necrosectomy. We hypothesise that the less invasive endoscopic step-up approach is superior to the surgical step-up approach in terms of clinical and economic outcomes. The TENSION trial is a randomised controlled, parallel-group superiority multicenter trial. Patients with (suspected) infected necrotising pancreatitis with an indication for intervention and in whom both treatment modalities are deemed possible, will be randomised to either an endoscopic transluminal or a surgical step-up approach. During a 4 year study period, 98 patients will be enrolled from 24 hospitals of the Dutch Pancreatitis Study Group. The primary endpoint is a composite of death and major complications within 6 months following randomisation. Secondary endpoints include complications such as pancreaticocutaneous fistula, exocrine or endocrine pancreatic insufficiency, need for additional radiological, endoscopic or surgical intervention, the need for necrosectomy after drainage, the number of (re-)interventions, quality of life, and total direct and indirect costs. The TENSION trial will answer the question whether an endoscopic step-up approach reduces the combined primary endpoint of death and major complications, as well as hospital stay and related costs compared with a surgical step-up approach in patients with infected necrotising pancreatitis.

Background: After an initial attack of biliary pancreatitis, cholecystectomy minimizes the risk of recurrent biliary pancreatitis and other gallstone-related complications. Guidelines advocate performing cholecystectomy within 2 to 4 weeks after discharge for mild biliary pancreatitis. During this waiting period, the patient is at risk of recurrent biliary events. In current clinical practice, surgeons usually postpone cholecystectomy for 6 weeks due to a perceived risk of a more difficult dissection in the early days following pancreatitis and for logistical reasons. We hypothesize that early laparoscopic cholecystectomy minimizes the risk of recurrent biliary pancreatitis or other complications of gallstone disease in patients with mild biliary pancreatitis without increasing the difficulty of dissection and the surgical complication rate compared with interval laparoscopic cholecystectomy. Methods/Design: PONCHO is a randomized controlled, parallel-group, assessor-blinded, superiority multicenter trial. Patients are randomly allocated to undergo early laparoscopic cholecystectomy, within 72 hours after randomization, or interval laparoscopic cholecystectomy, 25 to 30 days after randomization. During a 30-month period, 266 patients will be enrolled from 18 hospitals of the Dutch Pancreatitis Study Group. The primary endpoint is a composite endpoint of mortality and acute re-admissions for biliary events (that is, recurrent biliary pancreatitis, acute cholecystitis, symptomatic/obstructive choledocholithiasis requiring endoscopic retrograde cholangiopancreaticography including cholangitis (with/without endoscopic sphincterotomy), and uncomplicated biliary colics) occurring within 6 months following randomization. Secondary endpoints include the individual endpoints of the composite endpoint, surgical and other complications, technical difficulty of cholecystectomy and costs. Discussion: The PONCHO trial is designed to show that early laparoscopic cholecystectomy (within 72 hours) reduces the combined endpoint of mortality and re-admissions for biliary events as compared with interval laparoscopic cholecystectomy (between 25 and 30 days) after recovery of a first episode of mild biliary pancreatitis. Trial registration: Current Controlled Trials: ISRCTN72764151

Background: In predicted severe acute pancreatitis, infections have a negative effect on clinical outcome. A start of enteral nutrition (EN) within 24 hours of onset may reduce the number of infections as compared to the current practice of starting an oral diet and EN if necessary at 3-4 days after admission. Methods/Design: The PYTHON trial is a randomised controlled, parallel-group, superiority multicenter trial. Patients with predicted severe acute pancreatitis (Imrie-score ≥ 3 or APACHE-II score ≥ 8 or CRP > 150 mg/L) will be randomised to EN within 24 hours or an oral diet and EN if necessary, after 72 hours after hospital admission. During a 3-year period, 208 patients will be enrolled from 20 hospitals of the Dutch Pancreatitis Study Group. The primary endpoint is a composite of mortality or infections (bacteraemia, infected pancreatic or peripancreatic necrosis, pneumonia) during hospital stay or within 6 months following randomisation. Secondary endpoints include other major morbidity (e.g. new onset organ failure, need for intervention), intolerance of enteral feeding and total costs from a societal perspective. Discussion: The PYTHON trial is designed to show that a very early (< 24 h) start of EN reduces the combined endpoint of mortality or infections as compared to the current practice of an oral diet and EN if necessary at around 72 hours after admission for predicted severe acute pancreatitis. Trial Registration: ISRCTN: ISRCTN18170985

Introduction. In patients with acute pancreatitis (AP), nutritional support is required if normal food cannot be tolerated within several days. Enteral nutrition is preferred over parenteral nutrition. We reviewed the literature about enteral nutrition in AP.Methods. A MEDLINE search of the English language literature between 1999–2009.Results. Nasogastric tube feeding appears to be safe and well tolerated in the majority of patients with severe AP, rendering the concept of pancreatic rest less probable. Enteral nutrition has a beneficial influence on the outcome of AP and should probably be initiated as early as possible (within 48 hours). Supplementation of enteral formulas with glutamine or prebiotics and probiotics cannot routinely be recommended.Conclusions. Nutrition therapy in patients with AP emerged from supportive adjunctive therapy to a proactive primary intervention. Large multicentre studies are needed to confirm the safety and effectiveness of nasogastric feeding and to investigate the role of early nutrition support.

Early computed tomography (CT) (within 4 full days after symptom onset) may be performed to distinguish acute pancreatitis (AP) from other intra-abdominal conditions or to identify early pancreatic necrosis. We analyzed practice and yield of early CT in patients with an established clinical diagnosis of AP in a Dutch cohort (EARL study). Multicenter observational study. Etiology, disease course, CT timing, Balthazar CT score, and clinical management were evaluated. First documented hospital admissions of 166 patients were analyzed. Etiology was biliary (42.8%), unknown (20.5%), alcoholic (18.1%), post-endoscopic retrograde cholangiopancreatography (11.4%), and miscellaneous (7.2%). In 89.2% (148/166), the disease course was mild. Out of 18 patients with severe AP, 11 eventually developed (peri)pancreatic necrosis. At least one CT (range 1-12) was performed in 47% (78/166) of all patients and in 62.8% (49/78) it was acquired within 4 full days after symptom onset. Practice, timing, and Balthazar CT score of early CTs were not significantly different between mild and severe AP. None of the early CTs showed necrosis and no alternative diagnoses were established. In 89.8% (44/49), clinical management was not altered after early CT. In 10.2% (5/49), prophylactic antibiotics were started, but in absence of necrosis. A CT scan was frequently acquired early in the course of AP, but its yield was low and had no implications with regard to clinical management. It seems prudent that clinicians should be more restrictive in the use of early CT, in particular in mild AP, to prevent unnecessary radiation exposure and to save costs.

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. 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. 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. Nederlands Trial Register NTR1150

The incidence and prevalence of acute and chronic pancreatitis have increased in Western countries. It is likely, the number of hospital admissions has increased correspondingly. To analyze the trends in hospital admissions in the Netherlands for acute and chronic pancreatitis from 1992 to 2004 and to forecast the number of admissions up to 2010. Analysis of hospital admissions for acute and chronic pancreatitis accumulated in a nationwide database. Curve fitting regression models were used to explore future trends. The number of acute pancreatitis admissions rose in 1992-2004 from 1,785 to 3,120 (74.8% increase). The overall 'annual number' of acute pancreatitis admissions increased from 11.8 to 19.2 per 100,000 person-years. The linear regression model predicted 3,205 [95% confidence intervals (CI), 3,111-3,299] and 3,537 (95% CI, 3,429-3,645) admissions for 2007 and 2010, respectively, a further increase of at least 9.9% in 2010 compared with 2004. In the 12-year time period, chronic pancreatitis admissions showed an increase of 75.4% (from 790 to 1,386). The overall 'annual number' of chronic pancreatitis admissions increased from 5.2 to 8.5 per 100,000 person-years. The cubic regression model predicted 1868 (95% CI, 1,619-2,117) and 3,173 (95% CI, 2,456-3,890) admissions for 2007 and 2010, respectively, an additional increase of 77.2% in 2010 compared with 2004. Hospital admissions for acute and chronic pancreatitis have increased substantially from 1992-2004. This trend will most likely continue for the near future and the burden and costs to the Dutch health care system will increase accordingly.