Neoplasms

Digestive System Diseases

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Rectal Neoplasms

Colorectal Neoplasms

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Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Intestinal Diseases

Rectal Diseases

Biological mesh reconstruction of the pelvic floor after extralevator abdomino perineal resection

Primary perineal closure after extralevator abdomino perineal resection

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.

Biological mesh assisted perineal closure

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.

Primary perineal closure

Gijsbert D. Musters, M.D.

Willem A. Bemelman, Prof, PhD, M.D.

Harm J. Rutten, M.D. PhD

Baljit Singh, M.D. PhD

Marcel G.W. Dijkgraaf, M.D.

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.

Biological Mesh Closure of the Pelvic Floor After Extralevator Abdomino Perineal Resection for Rectal Cancer

Long-term Results of Biological Mesh Closure of the Pelvic Floor After Extralevator Abdominoperineal Resection for Rectal Cancer

uncomplicated perineal wound healing is defined as a Souphampton wound score less than II

LifeCell

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Biological mesh reconstruction of the pelvic floor after extralevator abdomino perineal resection

Biological mesh assisted perineal closure: 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.

Biological Mesh Closure

Primary perineal closure after extralevator abdomino perineal resection

Primary perineal closure: 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.

Primary Perineal Closure

Total

Age, Continuous

Sex: Female, Male

there were 2 drop-outs in the biological mesh group because no extralevator APR was performed, and 1 drop-out in the primary closure group because patient died preoperatively because of brain metastasis

prof. dr. P.J. Tanis

2 drop-outs in the biological mesh group and 1 drop-out in de primary perineal closure group

30-day Uncomplicated Perineal Wound Healing

Overall Study

Skin and Connective Tissue Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

Implant based Breast Reconstruction with ADM. Both arms will undergo skin or nipple sparing mastectomy and immediate breast reconstruction with implants. Patients in group B with ADM and partial submuscular coverage.

Breast reconstruction without ADM. Both arms will undergo skin or nipple sparing mastectomy and immediate breast reconstruction with implant. Patients in group B will be reconstructed with implant and total submuscular coverage.

If the patient wishes to undergo immediate implant based reconstruction, and meets the selection criteria for entering the study, she is randomly selected to be treated according to Group A or Group B. Group A (no intervention) will be reconstructed with expander or anatomical gel implant without ADM, using complete muscle coverage. Group B (Intervention) will be reconstructed with expander or anatomical gel implant using partial muscle coverage in conjunction with ADM.

Reconstruction with ADM.

Mastectomy for invasive or pre-invasive breast cancer

Skin or nipple sparing mastectomy

Immediate breast reconstruction with implant

Reconstruction with implant

Implant based breast reconstruction with total submuscular coverage

Total submuscular coverage

Implant based breast reconstruction with partial submuscular coverage

Partial submuscular coverage

Fredrik Lohmander, MD

To evaluate breast reconstruction with implants using biological mesh (Strattice™) in the setting of breast cancer treatment.

OBJECTIVES: To evaluate the outcome of immediate breast reconstruction with Acellular Dermal Matrix (Strattice™), measuring safety, effectiveness, and costs. The primary outcome measure is number of unplanned surgical procedures.

STUDY DESIGN: A prospective randomized multicenter trial. One hundred and twenty patients with breast cancer will be enrolled into the study. Study duration will be two years from time of primary cancer surgery.

TRIAL DESIGN This is a randomized controlled multicenter trial, comparing IBR without (group A) and with (group B) the use of ADM. Participants eligible for the study are patients with breast cancer, planned for mastectomy, who wishes IBR with implants. Each participant is individually randomized to either be reconstructed using implants with total submuscular coverage (A) or reconstruction with ADM and partial muscle coverage (B).

Method of assigning patients to treatment groups:

After signing and dating the informed consent the patient is entered into the study. If all inclusion and none of the exclusion criteria are full filled, the patient will be randomized to group A or group B.

TREATMENT/ INTERVENTION The decision and treatment plan advocating mastectomy is based on multi disciplinary conference (MDT), and the diagnosis of invasive or pre-invasive (in situ) breast cancer is made on triple assessment. If the patient wishes to undergo immediate implant based reconstruction, and meets the selection criteria for entering the study, she is randomly selected to be treated according to Group A or Group B. Group A will be reconstructed with expander or anatomical gel implant without ADM, using complete muscle coverage. Group B will be reconstructed with expander or anatomical gel implant using partial muscle coverage in conjunction with ADM.

Randomization at enrollment is made with regard to the use of ADM or not, so both expander and direct-to-implant techniques will be utilized in both groups, depending on the quality of skin flaps at time of surgery.

RANDOMIZATION TYPE Patients will be allocated to treatment according to permuted block technique. The actual randomization will be performed using computer based system located at Regional Cancer Center (RCC) within Karolinska Institutet. In this system inclusion and exclusion criteria will be automatically checked before patients are randomized to treatment. The randomization process will be stratified for the participating units.

STATISTICAL METHODS The main endpoint to be analyzed is the proportion of unplanned reoperations after the initial breast reconstruction. The difference in proportions between the two groups will be presented as a difference in proportion together with a 95% confidence interval. Differences will be tested using Fishers Exact Test. Logistic regression will be used to take into account possible confounding factors.

STUDY MANAGEMENT Data recording: The investigators will ensure that all data from patient visits are entered promptly in ink, in the case report forms (CRF). The principal investigator must sign the final CRF page to attest to the accuracy and completeness of the data. The data from the CRFs are then transferred to a database.

Monitoring and audit: At periods not exceeding 3 months, centers will be contacted to discuss the progress of the trial, with the purpose to verify CRF data against source records for accuracy of data recording and collection.

Breast Reconstruction With Acellular Dermal Matrix in the Setting of Breast Cancer Treatment

Immediate Breast Reconstruction With or Without the Use of Acellular Dermal Matrix: A Randomized Controlled Multicenter Study

Follow-up time after primary surgery is 24 months.

To measure aesthetic outcome between the two study groups using a 6- point scale. The evaluation will be done by three independent groups consisting of lay people, professionals (breast/ plastic surgeons) and patient evaluation. The aesthetic evaluation will be based on the pre and postoperative photos.

To measure any difference between the two study groups in complication rates.

To compare the total number of surgical procedures (planned or unplanned) between the two study groups).

A cost-benefit analysis comparing the cost for an IBR with implant without ADM, vs. IBR with ADM (Strattice™) during a 24 months follow-up time.

Measure Quality of Life in both groups, using the EORTC QLQ-C30 (Generic tool), EORTC-BR23 (Breast cancer specific tool), EORTC-BRR (Specific for breast reconstruction).

Karolinska Institutet

Karolinska University Hospital

Fredrik Lohmander MD

Wounds and Injuries

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

The intervention consists of perinal reconstruction using biological mesh (Cellis prosthesis from Meccellis Biotech, reference C1015E size 10x15cm)

The intervention consists of perinal reconstruction by primary perineal wound closure

The intervention consists of suturing a biological mesh in the pelvic floor defect. The mesh will be sutured at each side of the coccyx or distal sacrum and directly to the residual pelvic floor muscle and fascia by using interrupted or continuous hand-sewn sutures with an appropriate amount of tension. The mesh that will be used is the Cellis prosthesis from Meccellis Biotech, reference C1015E which size is 10x15cm.

Biological mesh

The intervention consists of stitching the ischioanal and subcutaneous fat using interrupted Vicryl sutures in one or two layers similar to primary perineal closure

Primary perineal wound closure

Etienne BUSCAIL, MD

Cindy CANIVET, CRA

Jean-Marc REGIMBEAU

Aurélien VENARA

Zaher LAKKIS

Eric Rullier

Arnaud ALVES

Anne DUBOIS

Bertrand TRILLING

Mehrdad JAFARI

Guillaume PIESSEN, MD

Guillaume PIESSEN

Eddy Cotte

Cécile De Chaisemartin

Cécilia CERIBELLI

Adeline GERMAIN

Emilie DUCHALAIS, MD

Emilie DUCHALAIS

Jérémie LEFEVRE

Jean-Jacques Tuech

Etienne Buscail, MD

Cindy Canivet, CRA

Abdominoperineal resection performed for anorectal tumors leaves a large pelvic and perineal defect causing a high rate of morbidity of the perineal wound (40 - 60 %). Biological meshes offer possibility for a new standard of perineal wound reconstruction. Perineal filling with biological mesh is expected to increase quality of life by reducing perineal morbidity.

Perineal wound problems after abdominoperineal resection (APR) in the context of cancer are frequent. These types of resection problems occur because of wound complications caused by large perineal defects. Indeed, perineal wound complications, perineal abscess, wound dehiscences, chronic fistulas and sinuses lengthen the hospital stays. Futhermore, the standardization of the surgery since the late 2000s and the extralevator technique lead a larger defect and increase i perineal complications.

Several strategies are used to decrease the complication rate. Closure by direct approximation of the pelvic muscles leads to a rate of major complication up to 57% depending on the series. Musculocutaneous flaps help to reduce this rate (16- 65%) but they generate their own morbidity, require experience and increase the costs of care. Finally, the use of biologic meshes since the beginning of 2010 seems to have improve the healing process. However, results are still variable and the only randomized study comparing direct closure and mesh closure showed no significant results at one year. Another ongoing randomized trial is comparing gluteus maximus flap to mesh closure and focusing on physical performances.

This increase in post-operative complications and their consequences causes an increase in costs. In addition, they affect the patients' quality of life and lead to a loss of productivity. From an oncological point of view, perineal scarring problems can cause a delay in the adjuvant therapeutic sequence. Few studies have highlighted the efficiency of perineal wound complications, using cost-effectiveness analyses. In order to clarify the best strategy comparing primary and mesh closure in term of cost effectiveness on perineal healing after ELAPE, we designed this randomized controlled trial.

Cost-utility of Two Strategies of Perineal Reconstruction After Abdominoperineal Resection for Anorectal Carcinoma

Cost-utility Evaluation of Two Strategies of Perineal Reconstruction After Abdominoperineal Resection for Anorectal Carcinoma: Perineal Filling With Biological Meshes vs. Primary Perineal Wound Closure

The primary endpoint in this study is based on the assessment of the incremental cost-utility ratio at 1 year, from the collective perspective between biological mesh perineal reconstructions versus. primary perineal closure in patients operated for anorectal carcinoma with proven rectal adenocarcinoma or anal canal epidermoid carcinoma.

The perineal wound healing will be assessed using the Southampton wound assessment scale (6-point scale ranging from 0=normal healing to V=deep or severe wound infection)

assessed on an 11-point Numeric Rating Scale (NRS) at baseline before surgical procedure and at least 3 times a day during hospital stay. Thereafter, patients will rate their pain intensity in a patient subject diary every day and immediately before each use of pain medication

Health related quality of life will be assessed using the EuroQOL EQ-5D-5L questionnaire

Perineal complications include:

* Perineal wound infection defined as a swelling of the wound or surrounding tissues with purulent discharge
* Breakdown of the perineal wound included any wound dehiscence, sinus or ulcer
* Pelvic abscess included a fluid collection in the pelvis
* Perineal evisceration defined by exposure of the pelvic cavity through the perineal wound
* Perineal hernia symptomatic or not
* Perineal sinus defined as an incomplete healing after 6 months

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Biological Mesh Closure of the Pelvic Floor After Extralevator Abdomino Perineal Resection for Rectal Cancer	NCT01927497	Rectal Cancer	Biological mesh... Primary perinea...	18 Years -	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Breast Reconstruction With Acellular Dermal Matrix in the Setting of Breast Cancer Treatment	NCT02061527	Breast Cancer	Reconstruction ... Skin or nipple ... Reconstruction ... Total submuscul... Partial submusc...	18 Years -	Karolinska University Hospital
Cost-utility of Two Strategies of Perineal Reconstruction After Abdominoperineal Resection for Anorectal Carcinoma	NCT02841293	Abdominoperinea...	Biological mesh Primary perinea...	18 Years -	University Hospital, Toulouse

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