Endoscopic Versus Surgical Step-Up Approach for Infected Necrotizing Pancreatitis (ExTENSION): Long-term Follow-up of a Randomized Trial

BACKGROUND & AIMS: Previous randomized trials, including the Transluminal Endoscopic Step-Up Approach Versus Minimally Invasive Surgical Step-Up Approach in Patients With Infected Pancreatic Necrosis (TENSION) trial, demonstrated that the endoscopic step-up approach might be preferred over the surgical step-up approach in patients with infected necrotizing pancreatitis based on favorable short-term outcomes. We compared long-term clinical outcomes of both step-up approaches after a period of at least 5 years. METHODS: In this long-term follow-up study, we reevaluated all clinical data on 83 patients (of the originally 98 included patients) from the TENSION trial who were still alive after the initial 6-month follow-up. The primary end point, similar to the TENSION trial, was a composite of death and major complications. Secondary end points included individual major complications, pancreaticocutaneous fistula, reinterventions, pancreatic insufficiency, and quality of life. RESULTS: After a mean followup period of 7 years, the primary end point occurred in 27 patients (53%) in the endoscopy group and in 27 patients (57%) in the surgery group (risk ratio [RR], 0.93; 95% confidence interval [CI], 0.65-1.32; P = .688). Fewer pancreaticocutaneous fistulas were identified in the endoscopy group (8% vs 34%; RR, 0.23; 95% CI, 0.08-0.83). After the initial 6-month follow-up, the endoscopy group needed fewer reinterventions than the surgery group (7% vs 24%; RR, 0.29; 95% CI, 0.09-0.99). Pancreatic insufficiency and quality of life did not differ between groups. CONCLUSIONS: At long-term follow-up, the endoscopic step-up approach was not superior to the surgical step-up approach in reducing death or major complications in patients with infected necrotizing pancreatitis. However, patients assigned to the endoscopic approach developed overall fewer pancreaticocutaneous fistulas and needed fewer reinterventions after the initial 6-month follow-up.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Postponed or immediate drainage of infected necrotizing pancreatitis (POINTER trial): study protocol for a randomized controlled trial

Background Infected necrosis complicates 10% of all acute pancreatitis episodes and is associated with 15–20% mortality. The current standard treatment for infected necrotizing pancreatitis is the step-up approach (catheter drainage, followed, if necessary, by minimally invasive necrosectomy). Catheter drainage is preferably postponed until the stage of walled-off necrosis, which usually takes 4 weeks. This delay stems from the time when open necrosectomy was the standard. It is unclear whether such delay is needed for catheter drainage or whether earlier intervention could actually be beneficial in the current step-up approach. The POINTER trial investigates if immediate catheter drainage in patients with infected necrotizing pancreatitis is superior to the current practice of postponed intervention. Methods POINTER is a randomized controlled multicenter superiority trial. All patients with necrotizing pancreatitis are screened for eligibility. In total, 104 adult patients with (suspected) infected necrotizing pancreatitis will be randomized to immediate (within 24 h) catheter drainage or current standard care involving postponed catheter drainage. Necrosectomy, if necessary, is preferably postponed until the stage of walled-off necrosis, in both treatment arms. The primary outcome is the Comprehensive Complication Index (CCI), which covers all complications between randomization and 6-month follow up. Secondary outcomes include mortality, complications, number of (repeat) interventions, hospital and intensive care unit (ICU) lengths of stay, quality-adjusted life years (QALYs) and direct and indirect costs. Standard follow-up is at 3 and 6 months after randomization. Discussion The POINTER trial investigates if immediate catheter drainage in infected necrotizing pancreatitis reduces the composite endpoint of complications, as compared with the current standard treatment strategy involving delay of intervention until the stage of walled-off necrosis

Practical photocatalytic trifluoromethylation and hydrotrifluoromethylation of styrenes in batch and flow

Styrenes represent a challenging class of substrates for current radical trifluoromethylation and hydrotrifluoromethylation methods due to a myriad of potential side reactions. Herein, we describe the development of mild, selective and broadly applicable photocatalytic trifluoromethylation and hydrotrifluoromethylation protocols for these challenging substrates. The methods use fac-Ir(ppy)3, visible light and inexpensive CF3I and can be applied to a diverse set of vinylarene substrates. The use of continuous-flow photochemical reaction conditions allowed to reduce the reaction time and increase the reaction selectivity

Novel bifunctional [16]anes₄-derived chelators for soft radiometals

The field of targeted radionuclide therapy is rapidly growing, highlighting the need for wider radionuclide availability. Soft Lewis acid ions, such as radioisotopes of platinum, rhodium and palladium, are particularly underdeveloped. This is due in part to a lack of compatible bifunctional chelators. These allow for the practical bioconjugation to targeting vectors, in turn enabling radiolabeling. The [16]andS(4) macrocycle has been reported to chelate a number of relevant soft metal ions. In this work, we present a procedure for synthesizing [16]andS(4) in 45% yield (five steps, 12% overall yield), together with a selection of strategies for preparing bifunctional derivatives. An ester-linked N-hydroxysuccimide ester (NHS, seven steps, 4% overall yield), an ether-linked isothiocyanate (NCS, eight steps, 5% overall yield) and an azide derivative were prepared. In addition, a new route to a carbon-carbon linked carboxylic acid functionalized derivative is presented. Finally, a general method for conjugating the NHS and NCS derivatives to a polar peptide (octreotide) is presented, by dissolution in water:acetonitrile (1:1), buffered to pH 9.4 using borate. The reported compounds will be readily applicable in radiopharmaceutical chemistry, by facilitating the labeling of a range of molecules, including peptides, with relevant soft radiometal ions

The effect of laparoscopic partial fundoplication on dysphagia, esophageal and lower esophageal sphincter motility

It has been suggested that dysphagia is less common after partial versus complete fundoplication. The mechanisms contributing to postoperative dysphagia remain unclear. The objective of the present prospective study was to investigate esophageal motility and the prevalence of dysphagia in patients who have undergone laparoscopic partial fundoplication. Symptoms, lower esophageal sphincter (LES) characteristics and esophageal body motility were evaluated prospectively in 62 patients before and after laparoscopic partial fundoplication: 33 women and 29 men with a mean age of 44 +/- 1.5 years (range, 21-71). The patients filled in symptom questionnaires and underwent stationary and ambulatory manometry and 24-h pH-metry before and after operation. A small but significant increase in LES pressure from 14.8 +/- 0.9 to 17.8 +/- 0.8 mmHg was seen after laparoscopic partial fundoplication. Further, LES characteristics and esophageal body motility were not different post- versus preoperation. Three months after surgery, dysphagia was present in eight patients. No differences in LES characteristics or body motility were present between patients with and without dysphagia. Six months after the operation dysphagia was present in only three patients (3.2% mild and 1.6% severe dysphagia). Adequate reflux control was obtained in 85% of the patients. Laparoscopic partial fundoplication offers adequate reflux control without affecting esophageal body motility and with a very low incidence of postoperative dysphagia

Pervaporation of ethanol from lignocellulosic fermentation broth

Pervaporation can be applied in ethanol production from lignocellulosic biomass. Hydrophobic pervaporation, using a commercial PDMS membrane, was employed to concentrate the ethanol produced by fermentation of lignocellulosic hydrolysate. To our knowledge, this is the first report describing this. Pervaporation carried out with three different lignocellulosic fermentation broths reduced the membrane performance by 17-20% as compared to a base case containing only 3. wt.% ethanol in water. The membrane fouling caused by these fermentation broths was irreversible. Solutions containing model lignocellulosic components were tested during pervaporation at the same conditions. A total flux decrease of 12-15%, as compared to the base case, was observed for each component except for furfural. Catechol was found to be most fouling component whereas furfural permeated through the membrane and increased the total flux. The membrane selectivity increased in the presence of fermentation broth but remained unchanged for all selected components. © 2012 Elsevier Ltd