Collagen Implant (Biological Mesh) Versus GM Flap for Reconstruction of Pelvic Floor After ELAPE in Rectal Cancer

Study Overview
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Brief Summary
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The trial compares two different techniques for reconstruction of the lesser pelvic floor after an extended abdominoperineal excision for locally advanced rectal cancer. The alternative reconstruction techniques in the trial are: a technique using a gluteus maximus myocutaneous flap or a technique using an acellular porcine collagen implant (biological mesh) The primary endpoint will be physical performance six months from operation and our hypothesis is that the technique using an acellular porcine implant will cause less impaired physical performance compared to the technique using a myocutaneous flap. The study is interventional, randomized and by definition a comparative effectiveness research project.

Detailed Description
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Extended abdominoperineal excision (EAPE) of the rectum is the potentially curative operation for rectal carcinomas too low for primary anastomosis, especially if the levator and sphincter musculature is infiltrated. This enlarged operation, when the levator musculature is excised en bloc with the rectum, creates a large defect. Primary closure is often not possible, and reconstruction with prosthetic material or a myocutaneous flap is necessary to avoid a perineal hernia. Implantation of a collagen sheet (biological mesh) has shown preliminary good results and on the other hand, the use of a gluteus myocutaneous flap is routine in many clinics. There is a lack of scientific evidence to prove which method is better for the reconstruction of the lesser pelvic floor. The current study aims to compare the two reconstruction techniques. Centres that treat locally advanced rectal cancers with the extended abdominoperineal excision of rectum (EAPE)[Holm et al 2007] can participate provided that: the operative technique is standardized according to the study protocol the centre/unit has resources for examinations of participants by a physiotherapist or a nurse the centre/unit has one investigator in charge of the study locally the centre/unit has an operative volume that enables at least 6 patients to be included/randomised during the anticipated three year study phase for inclusions Centres that do not operate the rectal cancers included in this study can participate by arranging the preoperative examination and physical tests as well as follow-up of patients that are referred to other centres for the operation. In these cases the operating centre cares for the randomisation, operation and start of postoperative rehabilitation while the study follow-up and final rehabilitation can be completed at the patients' primary referral hospital. The primary referral hospital needs a site investigator in charge of study patients just like centres that do the operations. Patients with primary or recurrent cancers of rectal origin can be included but individual patients can be included only once. Concomitant therapies are allowed and preoperative or postoperative radiation therapy and/or chemotherapy may be given or not according to local multidisciplinary team (MDT) decisions.

Official Title
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Nordic Extended Abdominoperineal Excision (NEAPE) Study, a RCT Comparing a Porcine Acellular Dermal Collagen Implant (Biological Mesh) With a Gluteus Maximus Flap for Reconstruction of Pelvic Floor After ELAPE in Rectal Cancer

Conditions
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Rectal Cancer, Defect of Floor of Lesser Pelvis

Intervention / Treatment
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* Procedure: Reconstruction with an acellular porcine dermal collagen implant (biological mesh)
* Procedure: Reconstruction with a gluteus maximus myocutaneous flap


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult (18 years or older) rectal cancer patients where wide resection of pelvic floor muscles together with rectum and anal canal have made reconstruction of pelvic floor necessary i.e. primary suture of pelvic floor in the midline is not possible. Resection of coccyx is optional. Exclusion Criteria: Age less than 18 years Very large resections including partial resection of sacrum and patients considered for bilateral flap reconstruction Large concomitant resection of vaginal wall where total (vaginal) wound closure is not an option Expected survival less than one year at operation Patient do not sign informed consent document

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Porcine collagen implant (biological mesh)<br>Reconstruction with an acellular porcine dermal collagen implant (biological mesh). | Procedure: Reconstruction with an acellular porcine dermal collagen implant (biological mesh)<br>* Reconstruction of floor of lesser pelvis with an acellular porcine dermal collagen implant (biological mesh) after extended excision of rectum including levator muscles in advanced low rectal cancer.<br>|
| Active Comparator: Gluteus maximus flap<br>Reconstruction with a gluteus maximus myocutaneous flap. | Procedure: Reconstruction with a gluteus maximus myocutaneous flap<br>* Reconstruction of floor of lesser pelvis with an gluteus maximus myocutaneous flap after extended excision of rectum including levator muscles in advanced low rectal cancer.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Performance in Timed-Stands Test | Timed-Stands test is a combined measure of physical performance depending on at least muscle strength, balance, tenderness of gluteal skin and muscles and co-ordination of motion. | 6 months after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in physical performance | Change in Timed-Stands Test performance | 3, 6 and 12 months after surgery compared with preoperative results | 
| Primary wound healing assessed with the Southampton Wound Assessment Scale | The Southampton Wound Assessment Scale is a validated measure of wound healing after surgery. | 3 months from operation | 
| Complications according to classification by Dindo-Clavien | The Dindo-Clavien classification of surgical complications is a validated instrument. | 3, 6 and 12 months after surgery | 
| Proportion of persistent perineal sinus or fistula | Proportion of patients with the wound healing defect of all patients in the particular study arm | 3, 6 and 12 months after surgery | 
| Ability to sit | Ability to sit is graded with a scale in three degrees. | 3, 6 and 12 months after surgery | 
| Change of pain and discomfort in gluteal region measured with VAS | A standard visual analogue scale (VAS) from 0-100 mm is used. | 3, 6 and 12 months after surgery compared to preoperative | 
| Pain and discomfort in gluteal region, spot measures with VAS | A standard visual analogue scale (VAS) from 0-100 mm is used. | 3, 6 and 12 months after surgery | 
| Change of quality of life measured with EQ-5D and EORTC forms C30 and CR29 | EQ-5D and EORTC are validated quality of life instruments | 3, 6 and 12 months after surgery compared to preoperative | 
| Quality of life spot measures | Quality of life at specified time points | 3, 6 and 12 months after surgery | 
| Length of hospital stay | Length of index hospital stay in days. | Six months after surgery | 
| Costs of surgical treatment | Hospital expenses converted to US$ | 12 months after surgery | 
| Quality-adjusted life years (QALYs gained) | Quality adjusted life year (QALY) is calculated using an quality of life utility index at repeated time points. The utility index is adjusted for the relevant background population. | 12 months after surgery | 
| Local recurrence | Local recurrence of rectal cancer detected by clinical or radiological investigation | Five years after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rectal neoplasms, reconstructive surgical procedure, bioprosthesis, surgical flaps, locomotion, lesser pelvis