title: Preoperative endoscopic versus percutaneous transhepatic biliary drainage in potentially resectable perihilar cholangiocarcinoma (DRAINAGE trial): design and rationale of a randomized controlled trial.
abstract: BACKGROUND
  Liver surgery in perihilar cholangiocarcinoma (PHC) is associated with high postoperative morbidity because the tumor typically causes biliary obstruction. Preoperative biliary drainage is used to create a safer environment prior to liver surgery, but biliary drainage may be harmful when severe drainage-related complications deteriorate the patients' condition or increase the risk of postoperative morbidity. Biliary drainage can cause cholangitis/cholecystitis, pancreatitis, hemorrhage, portal vein thrombosis, bowel wall perforation, or dehydration. Two methods of preoperative biliary drainage are mostly applied: endoscopic biliary drainage, which is currently used in most regional centers before referring patients for surgical treatment, and percutaneous transhepatic biliary drainage. Both methods are associated with severe drainage-related complications, but two small retrospective series found a lower incidence in the number of preoperative complications after percutaneous drainage compared to endoscopic drainage (18-25% versus 38-60%, respectively). The present study randomizes patients with potentially resectable PHC and biliary obstruction between preoperative endoscopic or percutaneous transhepatic biliary drainage.
  
  
  METHODS
  The study is a multi-center trial with an "all-comers" design, randomizing patients between endoscopic or percutaneous transhepatic biliary drainage. All patients selected to potentially undergo a major liver resection for presumed PHC are eligible for inclusion in the study provided that the biliary system in the future liver remnant is obstructed (even if they underwent previous inadequate endoscopic drainage). Primary outcome measure is the total number of severe preoperative complications between randomization and exploratory laparotomy. The study is designed to detect superiority of percutaneous drainage: a provisional sample size of 106 patients is required to detect a relative decrease of 50% in the number of severe preoperative complications (alpha = 0.95; beta = 0.8). Interim analysis after inclusion of 53 patients (50%) will provide the definitive sample size. Secondary outcome measures encompass the success of biliary drainage, quality of life, and postoperative morbidity and mortality.
  
  
  CONCLUSIONS
  The DRAINAGE trial is designed to identify a difference in the number of severe drainage-related complications after endoscopic and percutaneous transhepatic biliary drainage in patients selected to undergo a major liver resection for perihilar cholangiocarcinoma.
  
  
  BACKGROUND
  Netherlands Trial Register [ NTR4243 , 11 October 2013].
authors.affiliation: Department of Surgery, Academic Medical Center, Meibergdreef 9, Room IWO-A1.119, 1105, AZ, Amsterdam, The Netherlands. j.k.wiggers@amc.nl.
authors.forename: Jimme K
authors.initials: JK
authors.lastname: Wiggers
authors.affiliation: Department of Surgery, Academic Medical Center, Meibergdreef 9, Room IWO-A1.119, 1105, AZ, Amsterdam, The Netherlands. r.j.coelen@amc.nl.
authors.forename: Robert J S
authors.initials: RJ
authors.lastname: Coelen
authors.affiliation: Department of Gastroenterology, Academic Medical Center, Amsterdam, The Netherlands. e.a.rauws@amc.nl.
authors.forename: Erik A J
authors.initials: EA
authors.lastname: Rauws
authors.affiliation: Department of Radiology, Academic Medical Center, Amsterdam, The Netherlands. o.m.vandelden@amc.nl.
authors.forename: Otto M
authors.initials: OM
authors.lastname: van Delden
authors.affiliation: Department of Surgery, Erasmus Medical Center, Rotterdam, the Netherlands. c.vaneijck@erasmusmc.nl.
authors.forename: Casper H J
authors.initials: CH
authors.lastname: van Eijck
authors.affiliation: Department of Surgery, Erasmus Medical Center, Rotterdam, the Netherlands. j.dejonge.1@erasmusmc.nl.
authors.forename: Jeroen
authors.initials: J
authors.lastname: de Jonge
authors.affiliation: Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. r.j.porte@umcg.nl.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Porte
authors.affiliation: Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. c.i.buis@umcg.nl.
authors.forename: Carlijn I
authors.initials: CI
authors.lastname: Buis
authors.affiliation: Department of Surgery, Maastricht University Medical Center and NUTRIM School for Translational Research in Metabolism, Maastricht, the Netherlands. chc.dejong@mumc.nl.
authors.forename: Cornelis H C
authors.initials: CH
authors.lastname: Dejong
authors.affiliation: Department of Surgery, University Medical Center Utrecht, Utrecht, the Netherlands. i.q.molenaar@umcutrecht.nl.
authors.forename: I Quintus
authors.initials: IQ
authors.lastname: Molenaar
authors.affiliation: Department of Surgery, Academic Medical Center, Meibergdreef 9, Room IWO-A1.119, 1105, AZ, Amsterdam, The Netherlands. m.g.besselink@amc.nl.
authors.forename: Marc G H
authors.initials: MG
authors.lastname: Besselink
authors.affiliation: Department of Surgery, Academic Medical Center, Meibergdreef 9, Room IWO-A1.119, 1105, AZ, Amsterdam, The Netherlands. o.r.busch@amc.nl.
authors.forename: Olivier R C
authors.initials: OR
authors.lastname: Busch
authors.affiliation: Clinical Research Unit, Academic Medical Center, Amsterdam, The Netherlands. m.g.dijkgraaf@amc.nl.
authors.forename: Marcel G W
authors.initials: MG
authors.lastname: Dijkgraaf
authors.affiliation: Department of Surgery, Academic Medical Center, Meibergdreef 9, Room IWO-A1.119, 1105, AZ, Amsterdam, The Netherlands. t.m.vangulik@amc.nl.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: van Gulik
mesh_terms: D001650:Bile Duct Neoplasms / Q000150:complications* / Q000601:surgery; D018281:Cholangiocarcinoma / Q000150:complications* / Q000601:surgery; D002779:Cholestasis / Q000601:surgery*; D004322:Drainage / Q000009:adverse effects* / Q000379:methods*; D016145:Endoscopy, Digestive System; D006498:Hepatectomy; D006801:Humans; D011300:Preoperative Care; D011788:Quality of Life; D012107:Research Design