Acronym
BIOPEX-2
Name of the study
Perineal wound closure using gluteal turnover flap or primary closure after abdominoperineal resection for rectal cancer: a randomised controlled multicenter trial
Researchers and contact information
Principal investigators:
Prof. dr. P.J. Tanis p.tanis@erasmusmc.nl Project leader
Dr. G.D. Musters g.d.musters@amsterdamumc.nl
Coordinating investigator:
S. Kreisel s.i.kreisel@amsterdamumc.nl
Study website:
www.biopex2studie.nl
Summary study
Rationale
About 700 patients per year undergo an abdominoperineal resection (APR) for distal rectal cancer (Dutch Colorectal Audit 2016). Neo-adjuvant (chemo)radiotherapy is often used to further improve loco-regional control. Morbidity after APR is substantial and mainly consisting of perineal wound problems in about 35% of the patients. lf primary healing of the perineal wound after APR does not occur, secondary healing can take up to one year, and there is even a small proportion of patients in whom a chronic perineal wound or fistula persists after one year. During this long period, intensive wound care is necessary. This results in a heavy burden on both patient and health care resources.
Objective
The high morbidity rate of the perineal wound has resulted in a continuing discussion on how to close the perineal defect after APR. Our research group recently published the BIOPEX-study (NL42094.018.12), in which 104 patients were randomized between primary perineal wound closure and biological mesh closure of the pelvic floor after APR with preoperative radiotherapy for rectal cancer. Similar uncomplicated perineal wound healing rate at 30 days (Southampton wound score < 2) was found: 63% versus 66%, respectively. The hypothesis behind this negative trial result is related to the perineal dead space between the skin and the biological mesh. Fluid will accumulate in this dead space with the risk of secondary contamination and abscess formation, leading to wound dehiscence and purulent discharge. Autologous tissue flaps have been suggested to improve perineal wound healing based on several cohort studies. At least in the Netherlands, these flaps are used
only for selected patients with the large defects and highest risk of wound problems, because of the more extensive surgery with added surgical trauma and operative time, and associated donor site morbidity. For these reasons, primary perineal closure (control arm of BIOPEX) is still the standard of care in the Netherlands.
A gluteal turnover flap (GT flap) is a small transposition flap from the unilateral adjacent perineal skin and subcutaneous fat, which is flipped into the perineal dead space, and stitched with the de-epithelialized dermis to the contralateral pelvic floor remnant. Subsequently, the perineal subcutaneous fat and skin are closed over the flap in the midline, thereby not adding a donor site scar. A small pilot study from our group showed that this is a promising solution for routine perineal closure after APR.
Study design
In this multicenter single blinded study, eligible patients will be randomized between pelvic floor reconstruction using a GT flap (intervention arm) and primary closure of the perineal defect (standard arm). The perineal wound healing will be evaluated at 14 days and 1, 3, 6 and 12 months post-operatively using the Southampton wound scoring system by an independent observer.
Study population
Patients aged older than 18 year undergoing abdominoperineal resection for rectal cancer.
Outcomes
he primary endpoint of the study is the percentage of uncomplicated perineal wound healing defined as a Southampton wound score of less than two at 30 days postoperatively. Secondary endpoints are perineal wound healing according to the Southampton wound grading at 14 days, 3, 6 and 12 months postoperatively, postoperative pain score, the effect of neo-adjuvant treatment on gluteal turnover flap healing, incidence of persistent perineal or presacral sinuses both clinically and by imaging (routine follow-up CT), need for re-intervention or re-admission related to perineal wound problems, incidence of symptomatic and asymptomatic perineal hernia during follow-up, length of hospital stay, and quality of life and urogenital function (EQ-5D, EORTC-30, EORTC-29, SF36, UDI-6, IIQ-7, IIEF, FSFI, FSDS-R).
Intervention
Control arm: Primary perineal closure after abdominoperineal resection for rectal cancer
Experimental arm: Gluteal turnover flap closure after abdominoperineal resection for rectal cancer
Participating centers:
Formally approved by central and local IRB
- Albert Schweitzer Ziekenhuis
- Amphia Ziekenhuis
- Amsterdam UMC (location AMC)
- Amsterdam UMC (location VUmc)
- Antoni van Leeuwenhoek
- Bravis Ziekenhuis
- Canisius Wilhelmina Ziekenhuis
- Catharina Ziekenhuis
- Deventer Ziekenhuis
- ErasmusMC
- Flevoziekenhuis
- IJsselland Ziekenhuis
- Laurentius Ziekenhuis
- OLVG
- Radboudumc
- Spaarne Gasthuis
- Tergooi
Formally approved by central IRB, working on receiving approval local IRB
1. Haga Ziekenhuis
2. Leicester University Hospital
3. Maastricht Universitair Medisch Centrum
4. Oxford University Hospital
5. Wales University Hospital
6. Zuyderland Medisch Centrum