title: Two-stage implant-based breast reconstruction compared with immediate one-stage implant-based breast reconstruction augmented with an acellular dermal matrix: an open-label, phase 4, multicentre, randomised, controlled trial.
abstract: BACKGROUND
  The evidence justifying the use of acellular dermal matrices (ADMs) in implant-based breast reconstruction (IBBR) is limited. We did a prospective randomised trial to compare the safety of IBBR with an ADM immediately after mastectomy with that of two-stage IBBR.
  
  
  METHODS
  We did an open-label, randomised, controlled trial in eight hospitals in the Netherlands. Eligible women were older than 18 years with breast carcinoma or a gene mutation linked with breast cancer who intended to undergo skin-sparing mastectomy and immediate IBBR. Randomisation was done electronically, stratified per centre and in blocks of ten to achieve roughly balanced groups. Women were assigned to undergo one-stage IBBR with ADM (Strattice, LifeCell, Branchburg, NJ, USA) or two-stage IBBR. The primary endpoint was quality of life and safety was assessed by the occurrence of adverse outcomes. Analyses were done per protocol with logistic regression and generalised estimating equations. This study is registered at Nederlands Trial Register, number NTR5446.
  
  
  RESULTS
  142 women were enrolled between April 14, 2013, and May 29, 2015, of whom 59 (91 breasts) in the one-stage IBBR with ADM group and 62 (92 breasts) in the two-stage IBBR group were included in analyses. One-stage IBBR with ADM was associated with significantly higher risk per breast of surgical complications (crude odds ratio 3·81, 95% CI 2·67-5·43, p<0·001), reoperation (3·38, 2·10-5·45, p<0·001), and removal of implant, ADM, or both (8·80, 8·24-9·40, p<0·001) than two-stage IBBR. Severe (grade 3) adverse events occurred in 26 (29%) of 91 breasts in the one-stage IBBR with ADM group and in five (5%) of 92 in the two-stage IBBR group. The frequency of mild to moderate adverse events was similar in the two groups.
  
  
  CONCLUSIONS
  Immediate one-stage IBBR with ADM was associated with adverse events and should be considered very carefully. Understanding of selection of patients, risk factors, and surgical and postsurgical procedures needs to be improved.
  
  
  BACKGROUND
  Pink Ribbon, Nuts-Ohra, and LifeCell.
authors.affiliation: Department of Plastic, Reconstructive, and Hand Surgery, VU University Medical Centre, Amsterdam, Netherlands; EMGO Institute for Health and Care Research Amsterdam, Amsterdam, Netherlands.
authors.forename: Rieky E G
authors.initials: RE
authors.lastname: Dikmans
authors.affiliation: Department of Plastic, Reconstructive, and Hand Surgery, VU University Medical Centre, Amsterdam, Netherlands; EMGO Institute for Health and Care Research Amsterdam, Amsterdam, Netherlands.
authors.forename: Vera L
authors.initials: VL
authors.lastname: Negenborn
authors.affiliation: Department of Plastic, Reconstructive, and Hand Surgery, VU University Medical Centre, Amsterdam, Netherlands; EMGO Institute for Health and Care Research Amsterdam, Amsterdam, Netherlands; Alexander Monro Breast Cancer Hospital, Bilthoven, Netherlands.
authors.forename: Mark-Bram
authors.initials: MB
authors.lastname: Bouman
authors.affiliation: Department of Plastic, Reconstructive, and Hand Surgery, VU University Medical Centre, Amsterdam, Netherlands; EMGO Institute for Health and Care Research Amsterdam, Amsterdam, Netherlands; Alexander Monro Breast Cancer Hospital, Bilthoven, Netherlands.
authors.forename: Hay A H
authors.initials: HA
authors.lastname: Winters
authors.affiliation: Department of Epidemiology and Biostatistics, VU University Medical Centre, Amsterdam, Netherlands.
authors.forename: Jos W R
authors.initials: JW
authors.lastname: Twisk
authors.affiliation: Department of Plastic, Reconstructive, and Hand Surgery, Meander Medical Centre, Amersfoort, Netherlands.
authors.forename: P Quinten
authors.initials: PQ
authors.lastname: Ruhé
authors.affiliation: Department of Plastic, Reconstructive, and Hand Surgery, Erasmus MC Cancer Institute, University Medical Centre Rotterdam, Rotterdam, Netherlands.
authors.forename: Marc A M
authors.initials: MA
authors.lastname: Mureau
authors.affiliation: Department of Plastic, Reconstructive, and Hand Surgery, VU University Medical Centre, Amsterdam, Netherlands; Alexander Monro Breast Cancer Hospital, Bilthoven, Netherlands.
authors.forename: Jan Maerten
authors.initials: JM
authors.lastname: Smit
authors.affiliation: Department of Plastic, Reconstructive, and Hand Surgery, Maastricht University Medical Centre, Maastricht, Netherlands.
authors.forename: Stefania
authors.initials: S
authors.lastname: Tuinder
authors.affiliation: Department of Plastic, Reconstructive, and Hand Surgery, University Medical Centre Groningen, Groningen, Netherlands.
authors.forename: Yassir
authors.initials: Y
authors.lastname: Eltahir
authors.affiliation: Department of Plastic, Reconstructive, and Hand Surgery, Haga Ziekenhuis, Den Haag, Netherlands.
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Posch
authors.affiliation: Department of Plastic, Reconstructive, and Hand Surgery, Haga Ziekenhuis, Den Haag, Netherlands.
authors.forename: Josephina M
authors.initials: JM
authors.lastname: van Steveninck-Barends
authors.affiliation: Department of Plastic, Reconstructive, and Hand Surgery, Orbis Medisch Centrum, Sittard, Netherlands.
authors.forename: Marleen A
authors.initials: MA
authors.lastname: Meesters-Caberg
authors.affiliation: Department of Plastic, Reconstructive, and Hand Surgery, Maastricht University Medical Centre, Maastricht, Netherlands.
authors.forename: René R W J
authors.initials: RR
authors.lastname: van der Hulst
authors.affiliation: Department of Plastic, Reconstructive, and Hand Surgery, VU University Medical Centre, Amsterdam, Netherlands.
authors.forename: Marco J P F
authors.initials: MJ
authors.lastname: Ritt
authors.affiliation: Department of Plastic, Reconstructive, and Hand Surgery, VU University Medical Centre, Amsterdam, Netherlands; EMGO Institute for Health and Care Research Amsterdam, Amsterdam, Netherlands. Electronic address: m.mullender@vumc.nl.
authors.forename: Margriet G
authors.initials: MG
authors.lastname: Mullender
mesh_terms: D062088:Acellular Dermis / Q000706:statistics & numerical data*; D000328:Adult; D019928:Breast Implantation / Q000379:methods*; D018427:Breast Implants; D001943:Breast Neoplasms / Q000473:pathology / Q000601:surgery*; D018270:Carcinoma, Ductal, Breast / Q000473:pathology / Q000601:surgery*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000473:pathology / Q000601:surgery*; D018275:Carcinoma, Lobular / Q000473:pathology / Q000601:surgery*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016462:Mammaplasty / Q000379:methods*; D008408:Mastectomy / Q000379:methods; D008875:Middle Aged; D009367:Neoplasm Staging; D009426:Netherlands; D011183:Postoperative Complications; D011446:Prospective Studies; D011788:Quality of Life; D012086:Reoperation; D012107:Research Design; D016896:Treatment Outcome