Biological Mesh Closure of the Pelvic Floor After Extralevator Abdomino Perineal Resection for Rectal Cancer
Condition: Rectal Cancer
MeSH terms: Rectal Neoplasms
Intervention: Biological mesh assisted perineal closure; Primary perineal closure
Intervention description: The eAPR procedure will be performed in an identical way as described for the control arm of the study, and this is preferably followed by an omental plasty. The intervention in the experimental arm consists of suturing an acellular biological mesh derived from porcine dermis in the pelvic floor defect (Strattice™, 6x10 cm). The mesh will be sutured at each side of the coccyx or distal sacrum with Prolene or PDS to the discretion of the surgeon. Laterally, the mesh is attached to the remainings of the levator complex and, anteriorly, to the transverse perineal muscle or posterior vaginal wall. A suction drain will be inserted and positioned on top of the mesh. The perineal subcutaneous fat and skin will be subsequently closed in layers similar to primary simple closure as performed in the standard arm.; The perineal phase of the APR will be performed according to the principles of an extralevator APR, which means that the levator muscles will be laterally transected in order to leave a muscular cuff around the tumour. 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 and ischioanal fat will be as limited as oncologically justified. Preferably, an omental plasty is positioned in the pelvic cavity following resection. Closure of the perineum in the control arm consists of stitching the perineal subcutaneous fat together using interrupted Vicryl sutures in one or two layers. Subsequently, the skin will be closed using interrupted sutures according to the preference of the surgeon. Placement of a transabdominal or transperineal drain will be at the discretion of the surgeon.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Enrollment: 104.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Rectal cancer; Extralevator abdominoperineal resection; Biological Mesh; Primary closure

Summary:

      Rationale: Approximately 800 abdominoperineal resections (APR) are performed for rectal
      cancer each year in the Netherlands. The extralevator approach (eAPR) reduces the rate of
      positive margins and improves oncological outcome in distal rectal cancer. However, wider
      excisions increase wound healing problems and development of perineal hernia. This has
      resulted in a progressive increase of the use of musculocutaneous flaps and biological meshes
      associated with a substantial increase of costs, which is not supported by proper data.

      Objective: The aim of this study is to determine the cost-effectiveness of pelvic floor
      reconstruction using a biological mesh after standardized eAPR with neo-adjuvant
      (chemo)radiotherapy.

      Study design: This is a multicenter study in which patients undergoing an eAPR are randomized
      between standard care using primary closure of the perineum and the experimental arm with
      assisted closure using a biological mesh.

      Study population: Patients with a clinical diagnosis of primary rectal cancer who are
      scheduled for eAPR after neo-adjuvant (chemo)radiotherapy. A total number of 104 patients
      will be randomized.

      Intervention: The intervention in the experimental arm consists of suturing a biological mesh
      derived from porcine dermis in the pelvic floor defect, followed by perineal closure similar
      to the control arm.

      Main study parameters/endpoints: The primary endpoint is the percentage of uncomplicated
      perineal wound healing (Souphampton wound score less than II at day 30). Secondary endpoints
      are hospital stay, incidence of perineal hernia, quality of life, and costs.

      Nature and extent of the burden and risks associated with participation, benefit and group
      relatedness: Both primary perineal closure and biological mesh assisted closure are being
      performed in daily clinical practise. The potential benefit resulting from participation of
      the study in patients randomized for biological mesh assisted closure may be a higher chance
      of uncomplicated perineal wound healing and lower perineal hernia rate. On the other hand,
      the use of a biological mesh has been associated with increased postoperative pain and seroma
      formation.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age of 18 years or higher.

          2. Planned for eAPR for primary rectal cancer.

          3. Life expectancy of more than 2 years.

          4. Ability to return for all scheduled and required study visits.

          5. Preoperative (chemo)radiotherapy.

          6. Written informed consent for study participation.

        Exclusion Criteria:

          1. Previous pelvic irradiation for other cancers (i.e. prostate cancer).

          2. Total exenteration or sacral resection above level S4/S5.

          3. Sensitivity to porcine derived products or polysorbate.

          4. Severe systemic diseases affecting wound healing (i.e. renal failure requiring
             dialysis, liver cirrhosis, and immune compromised status like HIV).

          5. Collagen disorders (i.e. Marfan).

          6. Enrolment in trials with overlapping primary endpoint or otherwise expected influence
             on wound healing (i.e. biological therapy like antiangiogenic agents).