Preoperative biliary drainage for periampullary tumors causing obstructive jaundice; DRainage vs. (direct) OPeration (DROP-trial)

BACKGROUND: Surgery in patients with obstructive jaundice caused by a periampullary (pancreas, papilla, distal bile duct) tumor is associated with a higher risk of postoperative complications than in non-jaundiced patients. Preoperative biliary drainage was introduced in an attempt to improve the general condition and thus reduce postoperative morbidity and mortality. Early studies showed a reduction in morbidity. However, more recently the focus has shifted towards the negative effects of drainage, such as an increase of infectious complications. Whether biliary drainage should always be performed in jaundiced patients remains controversial. The randomized controlled multicenter DROP-trial (DRainage vs. Operation) was conceived to compare the outcome of a 'preoperative biliary drainage strategy' (standard strategy) with that of an 'early-surgery' strategy, with respect to the incidence of severe complications (primary-outcome measure), hospital stay, number of invasive diagnostic tests, costs, and quality of life. METHODS/DESIGN: Patients with obstructive jaundice due to a periampullary tumor, eligible for exploration after staging with CT scan, and scheduled to undergo a "curative" resection, will be randomized to either "early surgical treatment" (within one week) or "preoperative biliary drainage" (for 4 weeks) and subsequent surgical treatment (standard treatment). Primary outcome measure is the percentage of severe complications up to 90 days after surgery. The sample size calculation is based on the equivalence design for the primary outcome measure. If equivalence is found, the comparison of the secondary outcomes will be essential in selecting the preferred strategy. Based on a 40% complication rate for early surgical treatment and 48% for preoperative drainage, equivalence is taken to be demonstrated if the percentage of severe complications with early surgical treatment is not more than 10% higher compared to standard treatment: preoperative biliary drainage. Accounting for a 10% dropout, 105 patients are needed in each arm resulting in a study population of 210 (alpha = 0.95, beta = 0.8). DISCUSSION: The DROP-trial is a randomized controlled multicenter trial that will provide evidence whether or not preoperative biliary drainage is to be performed in patients with obstructive jaundice due to a periampullary tumor

Visualizing codon usage within and across genomes : concepts and tools

Cost and time of genome sequencing have plummeted over the last decade. This leads to explosive growth of genetic databases and development of novel sequencing-based approaches to study various biological phenomena. The database growth was particularly beneficial for investigation of protein-coding sequences at the codon level, requiring the access to large sets of related genomes. Such studies are expected to illuminate biological forces that shape primary structure of coding sequences and predict their evolutionary trajectories more precisely. In addition to fundamental interest, codon usage studies are of ample practical value, for example, in drug discovery and genomic medicine areas. Nevertheless, the depth of our understanding of codon-related issues is currently shallower as compared to what we know about nucleotide and amino acid sequences. Besides the lack of adequate datasets in the early days of molecular biology, codon usage studies, in our opinion, suffer from underdevelopment of easy-to-use tools to analyze and visualize how codon sequence changes along the gene and across the homologous genes in course of evolution. In this review, we aim to describe main areas of codon usage studies with an emphasis on the tools that allow visual interpretation of the data. We discuss underlying principles of different approaches, what kind of statistics lends confidence in their results and what has to be done to further boost the field of codon usage research