Synthetic and Biological Prostheses in Reconstructive Pelvic Floor Surgery

1. Synthetic and Biological Prostheses in Reconstructive Pelvic Floor Surgery Menchem Alcalay, MD Head, Urogynecology Unit Department of Ob Gyn Chaim Sheba Medical Center

2. Recurrence Prolapse Rate • 29% of women who had surgery for GSI or POP. 1 • 10-20 % of patients will require further intervention after failed primary continence surgery. 2 1 Olsen AL , et al. .Obstet Gynecol 1997;89:501–506. 2 Kholi N et al. Am J Obstet Gynecol 1996;175:1476–1482.

3. Attributing Factors to Failure • Inappropriate choice of procedure • Inappropriate suture material • Lack of surgical expertise • Inherent deficiencies in tissue quality • Inherent deficiencies in post operative healing • Persistent intra abdominal pressure

4. Surgical Principles of Abdominal Hernia Repair • In failure case - reinforcement of the repair by prosthetic graft. • The graft should be left with no tension.

5. Ideal Prostheses • Biocompatible • Inert • Lack of allergic / inflammatory response • Sterile • Non carcinogenic • Resistant to mechanical stress • Available and affordable

6. Classification of Prosthetic Surgical Grafts

7. Xenografts • Porcine or bovine derived tissue • Ready availability • Lack of ethical implications regarding human tissue usage • No significant inflamatory response in animal trials • Remodeling with collagenous infiltration • FDA approval of animals (porcine small intestinal mucosa or bovine pericardium)

8. Classification of Reconstructive Pelvic Surgery

9. Abdominal Sacrocolpopexy

10. Closure of the Cul De Sac

11. Development of the Presacral Area

12. Suturing the Mesh to the Vaginal Vault

13. Attachment of the Mesh to the Presacral Space using Staples or Sutures

14. Abdominal SacrocolpopexyLaparotomy Author n Prosthesis Follow up Success Complications Rust 12 Mersilene 9-42 100% Nill Symonds 17 Teflon 60-360 88% Nill Adison 56 Mersilene 6-126 89% Nill Drutz 15 Marlex 3-93 93% 1 sepsis - mesh removal Snyder 147 78 Gore Tex 60 73% 4 mesh erosions 65 Dacron Creighton 23 Mersilene 6-32 91% 2 sinuses - removal mesh Valaitis 43 Teflon 3-91 91% 1 sepsis - mesh removal Visco 273 269 Mersilene 1-87 - 15 erosions 4 Gore Tex Kholi 57 47 Marlex 2-50 100% 5 mesh erosions 10 Mersilene 2 suture erosions

15. Experience of Abdominal Sacrocolpopexy • 203 patients for 5 years • 137 had previous failed surgery • Recurrent vault prolapse - 2% • 14 (7%) developed rectocele requiring surgery • 24 (12%) developed GSI requiring surgery • Mesh erosion in 4 (2%) Carey MP, Dwyer PL, Curr Op Ob Gyn 2001;13:499-505

16. Laparoscopic SacrocolpopexyResults • The laparoscopic procedure is long and has specific complications such as: • Mesh rejection • Massive bleeding from the presacral space • 77 cases who underwent laparoscopic SC with mean FU of 1 year* : • 1 recurrent cystocele who needs repair • 2 cases of recurrent GSI that were operated • Operative time: 292 to 180 minutes. * Cosson M et al. J Gynecol Obstet Biol Reprod (Paris) 2000 ;29:746-750.

17. Laparoscopic SacrocolpopexyResults • 19 patients underwent a sacral colpopexy, modified culdoplasty, and Burch urethropexy. • Six paravaginal and 13 posterior vaginal repairs were performed. • At 1 year, one patient had mild genuine stress incontinence (93% cure rate) and none had vault eversion (100% cure rate). Two patients had grade 1 cystocele; one had grade 1 and two grade 2 rectoceles. Ross JW. J Am Assoc Gynecol Laparosc 1997 Feb;4(2):173-83

18. Laparoscopic SacrocolpopexyResults • Reported 15 cases of laparoscopic ASC who were followed for 3-40 months. • Cure rate for apical prolapse: 100% • 1 patient required laparotomy for massive presacral bleeding. Nezhat CH, Nezhat F, Nezhat C. Obstet Gynecol 1994 ;84:885-8.

19. Laparoscopic SacrocolpopexyResults • 76 patients underwent the procedure 1993-1999 • 35 had also GSI • Operating time: 100 - 345 minutes • Mean hospital stay 4.9 days (2-10) • Correction of the prolapse: 96% • Complications: 1 small injury to colon 1 1 conversion to laparotomy - CO2 Bruyere F et al. Prog Urol 2001 Dec;11(6):1320-6

20. Anterior Compartment

21. Anterior Colporrhaphy Prosthetic Reinforcement Results • 24 women with recurrent cystocele had to classical repair or Marlex mesh repair. • 2 years follow up • Cystocele recurrence - 4/12 control 0/12 mesh p<0.05 • Mesh related complications - 3/12 Julian TM. Am J Obstet Gynecol 1996 Dec;175(6):1472-5

22. Prospective randomized trial of polyglactin 910 mesh to prevent recurrence of cystoceles and rectoceles • RCT comparing 160 patients with and without polyglactin 910 mesh. • At 1 yr follow-up recurrent cystocele: Beyond mid vaginal plane (p=0.02): non mesh group – 43% mesh group – 25% To the hymenal ring (p=0.04): non mesh group – 10% mesh group – 2.5% • 13 recurrent rectoceles were noted - no differences between groups. • Polyglactin 910 mesh was found to be useful in the prevention of recurrent cystoceles Sand P et al. Am J Obstet Gynecol 2001 Jun;184(7):1357-62

23. Anterior colporrhaphy: a randomized trial of three surgical techniques • 3 techniques: standard (ST), standard plus polyglactin 910 mesh (ST+), or ultralateral anterior colporrhaphy (ULT) • 109 patients underwent operation, and 83 patients (76%) returned for follow-up • FU - 23.3 months; satisfactory or optimal results: ST - 30% ST+ - 42% ULT – 46% • These 3 techniques of anterior colporrhaphy provided similar anatomic cure rates and symptom resolution for anterior vaginal prolapse repair. The addition of polyglactin 910 mesh did not improve the cure rate compared with standard anterior colporrhaphy. Weber A et al. Am J Obstet Gynecol 2001 Dec;185(6):1299-304

24. Anterior Compartment Surgery with Prosthetic Reinforcement

25. Anterior Colporrhaphy Reinforced with Four Corner Anchored Polypropylene Mesh • 38 patients – dissection to ATFP • Follow up – 21 (12-29) months • Success rate – 87% • Concomitant SI – 100% cure with TVT (n=8) • De novo SI – 16.7% (n=5) • Erosions – 10.5% (n=4) • Risk factors for failure – DM, chronic cough Hung MJ et al. Int Urogynecol J Pelvic Floor Dysfunct. 2004;15(6):399-406

26. Perigee System for Anterior Prolapse Repair • Large-pore monofilament Polypropylene mesh system for correcting central defect and four self-attached horns for correcting lateral defect. • The implanted procedure consist of four steps: • 1) Lateral vaginal wall dissection as far as ischiopubic rami • 2) Performance of two upper marks at genitofemoral fold and two lower marks at 2 cm laterally and 3 cm lower • 3) Insertion of the upper needles parallel to the ischiopubic rami and connection with the mesh's "arms" plus insertion of the lower needles vertically and connection with mesh's "legs" • 4) Adjusting the mesh with free tension.

27. Transobturator correction of cystoceleInitial results • 15 patients • FU – 3 months • POP-Q points pre 6 wks 3 mon Aa +0.09 -3.00 -2.73 Ba +1.73 -2.82 -2.82 • No major complications Palma A et al. Actas Urol Esp. 2005 Jan;29(1):89-92.

28. Cochrane Systematic Review Surgical Management of POP in Women – 10/2004 • Standard anterior repair was associated with more recurrent cystoceles than when supplemented by Vycril mesh overlay (RR 1.39, 95% CI 1.02-1.90). • Data on morbidity and other clinical outcomes were too few for reliable comparisons. Maher C et al. The Cochrane Database on Systematic Reviews 2005 Issue 3

29. Anterior Compartment Repair with Prosthetic Reinforcement • Mixed evidence supporting prosthetic reinforcement in primary cystocele repair • Prosthetic graft does appear to improve outcome of recurrent cystocele • Variable risk of erosion • Erosion problem may be overcome by xenograft, but long term durability is unknown.

30. Posterior Compartment

31. Posterior Compartment Reinforcement • Standard technique (post. Colp.) with mesh interposition • Bilateral mesh fixation to SSL with mesh interposition into the recto vaginal septum • Insertion of sling at the level of ischiac spines with mesh attachment to the sling • Posterior IVS with mesh • Apogee

32. Mesh Ersosions • Slings • 1% Prolene • 31% Gore Tex • Abdominal sacrocolpopexy • 1.7% Prolene • 20% Teflon

33. What is Small Intestinal Submucosa (SIS)? • SIS is a natural biomaterial harvested from the porcine small intestine and made into a biocompatible medical product using a patented process. • The final product is a three-dimensional, extracellular matrix (ECM) comprised of collagen, non-collagenous proteins and other biomolecules including glycosaminoglycans, proteoglycans, and glycoproteins. • SIS is dried, packaged and sterilized, permitting long-term storage at room temperature. • SIS is fabricated into a variety of shapes and thicknesses, and is easily rehydrated and handled during surgery.

34. Natural Extracellular Matrix Range of additional components Proteins Carbohydrates Glycosaminoglycans (GAG) Proteoglycans (PG) Glycoproteins (GP) Collagen Lipids

35. BIOLOGICAL MESHES

36. Matrix Sequence SIS is gradually replaced as the body reinforces and rebuilds the weakened site. Following implantation,tissues adjacent to the SIS matrix begin to deliver cells and nutrients. Cells rapidly invade the SIS matrix. Capillary growth follows allowing more nutrients and cells to enter the matrix. The body’s tissue grows completely into the surgical site while SIS maintains the needed tissue support.

37. SIS After 7 Days Area of Overlying Skin, Superficial Fascia, and Adipose Tissue The SIS is already being invaded by adjacent cells. A mild inflammatory response is occurring and matrix deposition by the cells has begun. The SIS remains largely intact at this time point. SIS Underlying Abdominal Muscle

38. SIS After 1 Month Area of Overlying Skin, Superficial Fascia, and Adipose Tissue The SIS continues to be invaded by cells. A mild inflammatory response is present as the matrix is gradually remodeled. The SIS layers gradually separate as the cells populate the graft site and secrete their own matrix. SIS Underlying Abdominal Muscle

39. SIS After 3 Months The delineation between SIS and the surrounding abdominal wall becomes difficult to distinguish as the SIS gradually takes on the appearance of the surrounding tissue. Except for a relative acellularity in comparison to the surrounding tissues, SIS can no longer be clearly identified. SIS Underlying Abdominal Muscle

40. SIS After 6 Months Area of Overlying Skin, Superficial Fascia, and Adipose Tissue The SIS can no longer be distinguished from the surrounding abdominal tissue. The abdominal wall has been remodeled and resembles normal fibroadipose tissue with extensive vascularity and organized collagen bundles. Occasionally, pieces of SIS-like tissue can be distinguished, but clear identification of the SIS is no longer possible. Area of SIS Implant (SIS not detectable) Underlying Abdominal Muscle

41. SIS After 1 Year Organized Collagenous Tissue SIS can no longer be seen, though the area of implant can be determined from the surrounding tissue due to the organized collagenous tissue remaining in the area. The area remains normally vascularized, and focal areas of muscle ingrowth are common. Any inflam-mation is completely resolved and the abdominal wall appears histologically normal. Muscle Ingrowth Underlying Abdominal Muscle

42. SIS After 2 Years The area of implant must be determined based on the location of the surrounding musculature and the fibroadipose tissue of the abdominal wall. There is no evidence of SIS and no evidence of inflammation. Muscle bundles and organized collagen can be seen in the area where the implant had been placed, but the area of implant cannot be discerned from the surrounding tissues. Muscle Organized Collagen Fat Overlying Abdominal Muscle Layer

43. Conclusions • Meshes are been used in reconstructive pelvic surgery for > 10 years • Meshes reduce the rate of failure in recurrent cases of cystoceles • The long term efficacy and potential morbidity associated with the new materials is unknwon • Current evidence favor Type I synthetic polypropilene grafts (erosion ; infection) • Xenografts are promising grafts