Gluteal turnover flap for closure of the perineal wound after abdominoperineal resection for rectal cancer, BIOPEX 2-study

Colorectal cancer (CRC) is one of the world*s most common forms of cancer. Of
which, about 700 patients per year undergo an abdominoperineal resection (APR)
for distal rectal cancer (Dutch Colorectal Audit 2016). This procedure entails
a radical resection of the rectum with en bloc resection of the anorectal
sphincter complex and (part) of the levator muscle with lymphadenectomy
according to the total mesorectal excision (TME) principle. Neoadjuvant
(chemo)radiotherapy is often used to further improve locoregional control.
Morbidity after APR is substantial and mainly consisting of perineal wound
problems in about 35% of the patients. If primary healing of the perineal wound
after APR doesn*t 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.

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 deepithelialized 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, following the principle of
filling perineal dead space.

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 postoperatively
using the Southampton wound scoring system by an independent observer. In
addition, CT scan of the pelvis as usually performed during oncological
follow-up, will be reviewed with respect to presacral or perineal sinuses and
perineal herniation. Quality of Life questionnaires will be administered to the
patient at each follow-up interval. In addition, the nature and severity of any
wound event, all medical or surgical interventions and or re-operations will be
collected.

Surgery can start with the abdominal or the perineal phase. The abdominal phase
of the APR can be performed via either laparoscopic or open surgery. The
perineal phase of the APR will be performed according to the principles of a
complete or limited extralevator APR, which means that the levator muscles will
be transected laterally in order to leave a muscular cuff around the resection
specimen or only at the site of the tumor. The coccyx will not be routinely
resected, but only if indicated based on surgical exposure or oncological
principles. The extent of excision of perineal skin will be as limited as
oncologically justified. An omentoplasty will not be standardly being
performed. A transabdominal drain will be placed and removed after 4 days or
when the drain production is beneath 100cc/24hours. Perineal closure will be
performed by a surgeon experienced with the PTP-flap. When this experience is
not sufficiently present at the local participating hospital, an experienced
surgeon from the Amsterdam UMC will perform or supervise the perineal phase at
the local participating hospital. The patient will be positioned either in
prone or lithotomy position as preferred by the operating surgeon. A shallow
semicircular incision is made in the right or left gluteal skin with a maximum
distance of about 2.5 centimeter from the adjacent perineal defect. The
half-moon shaped skin island is deepithelialized. The subcutaneous fat is
transected lateral from the perforator(s) down to the gluteal fascia in a 45
degree angle. Thereafter, the subcutaneous flap is placed into the perineal
defect and fixed to the pelvic floor remnants with Vycril 2.0 sutures. The
ischioanal fat is sutured together using interrupted 2.0 Vicryl sutures.
Afterwards, the subcutaneous fat will be closed using interrupted 2.0 Vicryl
sutures. A Redon drain (CH10) will standardly be placed between these layers
and removed after 14 days or when the production is beneath the 30cc/24hours.
Subsequently, the skin will be closed using interrupted Vycril 3.0 sutures. Dry
gauze will be placed against the wound and will be changed two times a day.
Postoperatively the ERAS protocol will be followed and the sutures will be
removed after 14 days at the outpatient clinic.

The potential benefit resulting from participation of the study in patients
randomized for GT flap closure may be a higher chance of uncomplicated perineal
wound healing and lower perineal hernia rate. The potential risks of a GT flap
are experiencing more pain than usual after the operation. In addition, it may
be that the GT flap does not heal and becomes necrotic after the operation.
These previously mentioned complications usually do not require any major
treatment. In exceptional cases, it may be necessary to remove the flap
partially or completely. This will then be performed through a local operation.
The use of a GT flap will not affect the strength or size of the buttocks.