title: Minimally invasive versus open distal pancreatectomy (LEOPARD): study protocol for a randomized controlled trial.
abstract: Observational cohort studies have suggested that minimally invasive distal pancreatectomy (MIDP) is associated with better short-term outcomes compared with open distal pancreatectomy (ODP), such as less intraoperative blood loss, lower morbidity, shorter length of hospital stay, and reduced total costs. Confounding by indication has probably influenced these findings, given that case-matched studies failed to confirm the superiority of MIDP. This accentuates the need for multicenter randomized controlled trials, which are currently lacking. We hypothesize that time to functional recovery is shorter after MIDP compared with ODP even in an enhanced recovery setting.
  
  
  
  LEOPARD is a randomized controlled, parallel-group, patient-blinded, multicenter, superiority trial in all 17 centers of the Dutch Pancreatic Cancer Group. A total of 102 patients with symptomatic benign, premalignant or malignant disease will be randomly allocated to undergo MIDP or ODP in an enhanced recovery setting. The primary outcome is time (days) to functional recovery, defined as all of the following: independently mobile at the preoperative level, sufficient pain control with oral medication alone, ability to maintain sufficient (i.e. >50%) daily required caloric intake, no intravenous fluid administration and no signs of infection. Secondary outcomes are operative and postoperative outcomes, including clinically relevant complications, mortality, quality of life and costs.
  
  
  
  The LEOPARD trial is designed to investigate whether MIDP reduces the time to functional recovery compared with ODP in an enhanced recovery setting.
  
  
  
  Dutch Trial Register, NTR5188 . Registered on 9 April 2015.
authors.affiliation: Department of Surgery, Academic Medical Center, PO Box 22660, Amsterdam, AZ 1105, The Netherlands.
authors.forename: Thijs
authors.initials: T
authors.lastname: de Rooij
authors.affiliation: Department of Surgery, Academic Medical Center, PO Box 22660, Amsterdam, AZ 1105, The Netherlands.
authors.forename: Jony
authors.initials: J
authors.lastname: van Hilst
authors.affiliation: Department of Surgery, Academic Medical Center, PO Box 22660, Amsterdam, AZ 1105, The Netherlands.
authors.forename: Jantien A
authors.initials: JA
authors.lastname: Vogel
authors.affiliation: Department of Surgery, St Antonius Hospital, PO Box 2500, Nieuwegein, EM 3430, The Netherlands.
authors.forename: Hjalmar C
authors.initials: HC
authors.lastname: van Santvoort
authors.affiliation: Department of Surgery, University Medical Center Groningen, PO Box 30 001, Groningen, RB 9700, The Netherlands.
authors.forename: Marieke T
authors.initials: MT
authors.lastname: de Boer
authors.affiliation: Department of Surgery, St Antonius Hospital, PO Box 2500, Nieuwegein, EM 3430, The Netherlands.
authors.forename: Djamila
authors.initials: D
authors.lastname: Boerma
authors.affiliation: Department of Surgery, Radboud University Nijmegen Medical Center, PO Box 9101, Nijmegen, HB 6500, The Netherlands.
authors.forename: Peter B
authors.initials: PB
authors.lastname: van den Boezem
authors.affiliation: Department of Surgery, Leiden University Medical Center, PO Box 9600, Leiden, ZA 2333, The Netherlands.
authors.forename: Bert A
authors.initials: BA
authors.lastname: Bonsing
authors.affiliation: Department of Surgery, Jeroen Bosch Hospital, PO Box 90153, Den Bosch, ME 5200, The Netherlands.
authors.forename: Koop
authors.initials: K
authors.lastname: Bosscha
authors.affiliation: Department of Surgery, Maasstad Hospital, PO Box 9100, Rotterdam, AC 3007, The Netherlands.
authors.forename: Peter-Paul
authors.initials: PP
authors.lastname: Coene
authors.affiliation: Department of Surgery, VU University Medical Center, PO Box 7057, Amsterdam, HV 1081, The Netherlands.
authors.forename: Freek
authors.initials: F
authors.lastname: Daams
authors.affiliation: Department of Surgery, Maastricht University Medical Center, PO Box 5800, Maastricht, AZ 6202, The Netherlands.
authors.forename: Ronald M
authors.initials: RM
authors.lastname: van Dam
authors.affiliation: Clinical Research Unit, Academic Medical Center, PO Box 22660, Amsterdam, DD 1100, The Netherlands.
authors.forename: Marcel G
authors.initials: MG
authors.lastname: Dijkgraaf
authors.affiliation: Department of Surgery, Erasmus University Medical Center, PO Box 2040, Rotterdam, CA 3000, The Netherlands.
authors.forename: Casper H
authors.initials: CH
authors.lastname: van Eijck
authors.affiliation: Department of Surgery, Onze Lieve Vrouwe Gasthuis, PO Box 95500, Amsterdam, HM 1090, The Netherlands.
authors.forename: Sebastiaan
authors.initials: S
authors.lastname: Festen
authors.affiliation: Department of Surgery, Onze Lieve Vrouwe Gasthuis, PO Box 95500, Amsterdam, HM 1090, The Netherlands.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Gerhards
authors.affiliation: Department of Surgery, Erasmus University Medical Center, PO Box 2040, Rotterdam, CA 3000, The Netherlands.
authors.forename: Bas
authors.initials: B
authors.lastname: Groot Koerkamp
authors.affiliation: Department of Surgery, University Medical Center Utrecht, PO Box 85 500, Utrecht, GA 3508, The Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Hagendoorn
authors.affiliation: Department of Surgery, Maasstad Hospital, PO Box 9100, Rotterdam, AC 3007, The Netherlands.
authors.forename: Erwin
authors.initials: E
authors.lastname: van der Harst
authors.affiliation: Department of Surgery, Catharina Hospital, PO Box 1350, Eindhoven, ZA 5602, The Netherlands.
authors.forename: Ignace H
authors.initials: IH
authors.lastname: de Hingh
authors.affiliation: Department of Surgery, Maastricht University Medical Center, PO Box 5800, Maastricht, AZ 6202, The Netherlands.|NUTRIM School for Nutrition and Translational Research in Metabolism, PO Box 5800, Maastricht, AZ 6202, The Netherlands.
authors.forename: Cees H
authors.initials: CH
authors.lastname: Dejong
authors.affiliation: Department of Surgery, VU University Medical Center, PO Box 7057, Amsterdam, HV 1081, The Netherlands.
authors.forename: Geert
authors.initials: G
authors.lastname: Kazemier
authors.affiliation: Department of Surgery, Medisch Spectrum Twente, PO Box 50 000, Enschede, KA 7500, The Netherlands.
authors.forename: Joost
authors.initials: J
authors.lastname: Klaase
authors.affiliation: Department of Surgery, University Medical Center Groningen, PO Box 30 001, Groningen, RB 9700, The Netherlands.
authors.forename: Ruben H
authors.initials: RH
authors.lastname: de Kleine
authors.affiliation: Department of Surgery, Radboud University Nijmegen Medical Center, PO Box 9101, Nijmegen, HB 6500, The Netherlands.
authors.forename: Cornelis J
authors.initials: CJ
authors.lastname: van Laarhoven
authors.affiliation: Department of Surgery, Jeroen Bosch Hospital, PO Box 90153, Den Bosch, ME 5200, The Netherlands.
authors.forename: Daan J
authors.initials: DJ
authors.lastname: Lips
authors.affiliation: Department of Surgery, Catharina Hospital, PO Box 1350, Eindhoven, ZA 5602, The Netherlands.
authors.forename: Misha D
authors.initials: MD
authors.lastname: Luyer
authors.affiliation: Department of Surgery, University Medical Center Utrecht, PO Box 85 500, Utrecht, GA 3508, The Netherlands.
authors.forename: I Quintus
authors.initials: IQ
authors.lastname: Molenaar
authors.affiliation: Department of Surgery, Isala Clinics, PO Box 10 400, Zwolle, AB 8025, The Netherlands.
authors.forename: Vincent B
authors.initials: VB
authors.lastname: Nieuwenhuijs
authors.affiliation: Department of Surgery, Isala Clinics, PO Box 10 400, Zwolle, AB 8025, The Netherlands.
authors.forename: Gijs A
authors.initials: GA
authors.lastname: Patijn
authors.affiliation: Department of Surgery, Reinier de Graag Gasthuis, PO Box 5011, Delft, GA 2600, The Netherlands.
authors.forename: Daphne
authors.initials: D
authors.lastname: Roos
authors.affiliation: Department of Surgery, Reinier de Graag Gasthuis, PO Box 5011, Delft, GA 2600, The Netherlands.
authors.forename: Joris J
authors.initials: JJ
authors.lastname: Scheepers
authors.affiliation: Department of Surgery, Amphia Hospital, PO Box 90 158, Breda, RK 4800, The Netherlands.
authors.forename: George P
authors.initials: GP
authors.lastname: van der Schelling
authors.affiliation: Department of Surgery, Medisch Spectrum Twente, PO Box 50 000, Enschede, KA 7500, The Netherlands.
authors.forename: Pascal
authors.initials: P
authors.lastname: Steenvoorde
authors.affiliation: Department of Surgery, Leiden University Medical Center, PO Box 9600, Leiden, ZA 2333, The Netherlands.
authors.forename: Rutger-Jan
authors.initials: RJ
authors.lastname: Swijnenburg
authors.affiliation: Department of Surgery, Amphia Hospital, PO Box 90 158, Breda, RK 4800, The Netherlands.
authors.forename: Jan H
authors.initials: JH
authors.lastname: Wijsman
authors.affiliation: Department of Surgery, Southampton University Hospital NHS Foundation Trust, Southampton, SO166YD, UK.
authors.forename: Moh'd
authors.initials: M
authors.lastname: Abu Hilal
authors.affiliation: Department of Surgery, Academic Medical Center, PO Box 22660, Amsterdam, DD 1100, The Netherlands.
authors.forename: Olivier R
authors.initials: OR
authors.lastname: Busch
authors.affiliation: Department of Surgery, Academic Medical Center, PO Box 22660, Amsterdam, DD 1100, The Netherlands. m.g.besselink@amc.nl.
authors.forename: Marc G
authors.initials: MG
authors.lastname: Besselink
mesh_terms: D000284:Administration, Oral; D000700:Analgesics / Q000008:administration & dosage; D002985:Clinical Protocols; D003362:Cost-Benefit Analysis; D004435:Eating; D002149:Energy Intake; D006304:Health Status; D017721:Hospital Costs; D006801:Humans; D010535:Laparoscopy / Q000009:adverse effects / Q000191:economics; D009426:Netherlands; D010147:Pain Measurement; D010149:Postoperative Pain / Q000209:etiology / Q000517:prevention & control; D010180:Pancreatectomy / Q000009:adverse effects / Q000191:economics / Q000379:methods*; D011788:Quality of Life; D020127:Recovery of Function; D012107:Research Design; D065287:Robotic Surgical Procedures / Q000009:adverse effects / Q000191:economics; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000700:Analgesics
keywords: Distal pancreatectomy; Laparoscopic; Minimally invasive; Pancreatic cancer; Pancreatic surgery; Robot-assisted