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Functional failure of fascia lata allografts
Functional failure of fascia lata allografts M.P. FitzGerald, MD,a J. Mollenhauer, PhD,b P. Bitterman, MD,c and L. Brubaker, MDa Chicago, Illinois OBJECTIVES: Fascia lata allografts are commonly used in urogynecologic procedures. Functional failure of several grafts has occurred, and such failure has been recognized as a materials problem in 12 patients. STUDY DESIGN: Twelve patients with failure of an initial urogynecologic procedure performed with irradiated and freeze-dried donor fascia lata grafts underwent reoperation. Portions of the implanted fascia lata grafts could be retrieved in 7 cases. Graft specimens underwent histologic processing followed by hematoxylin and eosin staining. RESULTS: Histopathologic analyses of the retrieved material demonstrated several ongoing processes in the failed grafts. A few grafts showed areas of ideal remodeling. Most grafts, however, showed areas of disorganized remodeling and areas of graft degeneration. Evidence of immune reaction to the graft was observed in some cases. CONCLUSION: The high materials failure rate associated with the use of irradiated and freeze-dried donor fascia lata grafts suggests that such tissue should not be used for urogynecologic procedures. (Am J Obstet Gynecol 1999;181:1339-46.)
Key words: Donor tissue, fascia lata, graft failure
Tissue bank fascia lata allografts are used in surgical procedures for pelvic reconstruction and genuine stress urinary incontinence. The longevity and the histologic fate of this material appear to be responsible for certain surgical failures. We reoperated on 12 patients. Our findings in these 12 cases form the basis of this report and offer insight into why such grafts might fail. Material and methods Patients. Twelve patients with previous irradiated and freeze-dried donor fascia lata graft implants have undergone reoperation at our center. Their charts and any available histologic data were reviewed. Donor fascia lata allograft processing. The donor fascia lata allografts under discussion were obtained from a tissue bank accredited by the American Association of Tissue Banks. Our supplier reports no previous notification of any clinical problems with the use of their fascia lata grafts in urogynecologic procedures and reports good success with the use of their fascia lata grafts in orthopedic procedures. All tissues were harvested from human cadavers with aseptic technique. The tissue was then preserved and perhaps underwent additional sterilization.
From the Division of Urogynecology and Reconstructive Pelvic Surgery,a the Department of Biochemistry,b and the Department of Pathology,c Rush–Presbyterian–St Luke’s Medical Center. Presented at the Twenty-fifth Scientific Meeting of the Society of Gynecologic Surgeons, San Diego, California, February 19-21, 1999. Reprints not available from the authors. Copyright © 1999 by Mosby, Inc. 0002-9378/99 $8.00 + 0 6/6/103117
Freeze-dried irradiated fascia lata grafts were prepared as follows: (1) A medical and social history was obtained from the donor’s next of kin. Donors with known risk factors for human immunodeficiency virus infection and hepatitis were excluded. (2) All tissues were retrieved under aseptic conditions and soaked in antibiotic solution. (3) Microbiologic cultures were obtained from tissues at the time of harvest, and serologic screens for human immunodeficiency virus, hepatitis B and C viruses, and human T-lymphotropic virus type 1 were performed, as was a rapid plasma reagin test. Any positive serologic test result led to exclusion of the donor. (4) Fascia lata grafts were freeze-dried and packaged. (5) Fascia lata grafts were terminally sterilized with 2.5 Mrad gamma irradiation. Surgical technique. Before implantation, the donor graft was soaked in sodium chloride solution for 20 minutes. Donor fascial grafts were used to construct suburethral slings without the need to harvest autologous rectus fascial tissue, as previously described.1 We used a sling of intermediate length (approximately 3 × 10 cm) that was attached to rectus fascial tissue with polytetrafluoroethylene (GORE-TEX; W.L. Gore & Associates, Inc, Flagstaff, Ariz) suture arms. When performing a sacrocolpopexy, we placed 2 or 3 polytetrafluoroethylene sutures into the anterior longitudinal ligament of sacrum at the level of S2 or S3. The peritoneum was opened over both the anterior vagina and the posterior vagina. Large pieces of fascial tissue (eg, 6 × 16 cm) were placed on the anterior and posterior vagina with polytetrafluoroethylene suture to form a Y-shaped graft. The peritoneum was not routinely 1339
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Fig 1. Gross appearance of attenuated sacrocolpopexy graft 12 months after implantation.
closed over the implant. Concomitant urogynecologic procedures were undertaken as indicated. All patients received perioperative intravenous antibiotic therapy (eg, 2 g cefoxitin intravenously every 8 hours for 24-72 hours). All patients were asked to observe postoperative restrictions, including avoidance of lifting >5 lb in weight and avoidance of placing anything in the vagina for 12 weeks. Reoperation and retrieval of graft remnants. At the time of reoperation for failure of the initial surgical intervention, any visible graft remnant was removed or sampled for pathologic evaluation. A reoperative surgical procedure without the use of donor fascia lata grafts was then performed as indicated. Any retrieved graft specimens were placed in 10% buffered formaldehyde solution and processed for paraffin embedding according to standard protocols. Serial longitudinal sections 4 µm in thickness were cut. Hematoxylin and eosin staining was performed. Results Clinical characteristics. We have used fascia lata allografts in 67 sacrocolpopexy procedures and 35 suburethral sling procedures. We have reoperated on 13 of those patients because of recurrence or persistence of the patient’s symptoms. As outlined in Table I, 6 patients with donor fascia lata graft slings and 6 patients with donor fascia sacrocolpopexy grafts underwent reoperation. Those 12 patients represent 12% of the total population of patients who had allografts placed. Almost all the patients in whom suburethral sling procedures were performed had initial subjective cure of their symptoms of stress urinary incontinence. Only the first patient listed in Table I had immediate return of her symptoms once the catheter was removed 1 week after the operation. In the other cases the symptom-free period lasted between 6 and 16 weeks.
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All patients who received sacrocolpopexy grafts had initial subjective cure of the symptoms of pelvic organ prolapse. This cure was objectively documented 3 months after the operation for all patients in the standing, straining position. The patients went on to have recurrence of symptoms between 7 and 11 months after the initial operation, and examination confirmed recurrent prolapse in all cases. Findings at reoperation. Reoperation occurred as early as 5 weeks after the initial procedure. We were able to retrieve graft remnants from a total of 7 patients. When we could not find any graft remnants, we were still always able to identify the former graft site by recovering intact suture knots that enclosed no tissue. Such suture knots were easily identifiable on the anterior longitudinal ligament of the sacrum. Graft remnants were retrieved in all but 1 case during reoperation after failed sacrocolpopexy. In 2 cases sacrocolpopexy grafts still linked the vaginal apex to the sacrum, although the patient clinically had recurrence of pelvic organ prolapse. These in situ grafts were narrow, attenuated, and lax, as illustrated in Fig 1. In other cases in which no graft remained between the vagina and the sacrum, large amounts of graft remnant could usually be identified on reopening of the peritoneum overlying the posterior vagina. Histopathologic characteristics. Fig 2, A, illustrates the microscopic appearance of a donor graft once it has been reconstituted in sodium chloride solution before implantation. The connective tissue forms an open array, with gaps between the connective tissue fibers. Donor fibrocyte nuclei are visible, but the overall cellular content of the graft is low. Fig 2, B, demonstrates the loose connective tissue that is attached to the allografts in some areas. These areas are more cellular. This cross-section of the graft also illustrates the spaces between the graft fibers that are present after processing. Fig 3, A, illustrates the microscopic appearance of a suburethral sling graft retrieved after 5 weeks. The cellularity is high, with host fibroblast proliferation and graft neovascularization. There is little evidence of remodeling into tissue resembling fascia or tendon. Instead, the graft tissue has reorganized to resemble noninflammatory scar tissue, with little linear orientation of fibroblasts or connective tissue. Some small areas of the graft demonstrate less cellularity and exhibit tissue degeneration. Fig 3, B, illustrates fat cells still present in the graft. Fig 3, C, illustrates the microscopic appearance of a sacrocolpopexy graft retrieved 7 months after implantation. At reoperation a narrow attenuated graft remained in place between the sacrum and the vagina. Away from the graft periphery there is evidence of some of the desired remodeling of the graft into a unit capable of withstanding stress. This area appears viable, with a linear orientation of fibrocytes cells within connective tissue. Other areas demonstrate high cellularity but have not re-
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Fig 2. Reconstituted donor fascia lata graft before implantation. A, Open connective tissue array. B, Loose connective tissue attached to graft. (A-B, Hematoxylin and eosin. Original magnification ×100.)
Table I. Initial surgical procedure at which donor graft was implanted, time to reoperation for initial surgical failure, and findings at reoperation Patient No.
Initial surgical procedure
Time to symptom recurrence
Time to reoperation
1 2 3 4 5 6 7
Suburethral sling Suburethral sling Suburethral sling Suburethral sling Suburethral sling Suburethral sling Sacrocolpopexy
1 wk 6 wk 4 mo 6 wk 3 mo 5 mo 6 mo
5 wk 3 mo 6 mo 9 mo 9 mo 6 mo 6 mo
8 9 10 11
Sacrocolpopexy Sacrocolpopexy Sacrocolpopexy Sacrocolpopexy
7 mo 9 mo 11 mo 9 mo
7 mo 12 mo 12 mo 17 mo
12
Sacrocolpopexy
7 mo
19 mo
Gross findings at reoperation
Softened fragmented graft in retropubic tunnels No graft remnants No graft remnants Softened fragmented graft pieces in bilateral retropubic tunnels No graft remnants No graft remnants Graft adherent to both sacrum and vagina but without graft in between Attenuated narrow graft in place No graft remnants Attenuated narrow graft in place No graft between vagina and sacrum but portions of graft on posterior vagina Graft portions at vaginal apex, on posterior vagina, and on sacrum
modeled in a linear fashion, yielding microscopic appearances similar to the scarlike tissue seen in Fig 2, A. Finally, other areas demonstrate widespread breakdown of the tissue architecture (Fig 3, D). Fig 3, E, illustrates microscopic findings of a sacrocolpopexy graft on retrieval after 1 year. At the time of reoperation a narrow attenuated sacrocolpopexy graft was found to be in situ between the posterior vagina and the anterior longitudinal ligament of the sacrum. On microscopic examination the graft can be seen to exhibit high cellularity and vascularity. The connective tissue is longitudinally aligned in many areas in a manner that might be predicted to be ideal although with atypically high cellularity. However, other, smaller areas demonstrate less organization. There is a significant level of white blood cell accumulation throughout the graft (Fig 3, F). Overall this graft appears to be viable, consistent with its persistence at the implanted location. The microscopic appearance of a graft retrieved from the posterior vaginal wall after 17 months is illustrated in
Fig No. 3, A and B
3, D 2 and 3, E 3, G 3, H
Fig 3, G. Overall the graft has high cellularity and vascularity. The structure of the graft is haphazard. This tissue would be expected to have low tensile strength because of its high vascularity. There is little evidence of immune response to the graft in this case. Fig 3, H, illustrates the specific site of probable graft rupture. This was a sacrocolpopexy graft retrieved 19 months after implantation. One extreme of the graft demonstrates a clear transition from an ideal type of remodeling through a short area of open connective tissue to the end of the graft, the point at which we presume the graft ruptured. Except at suture sites a host immune response to the graft is not a feature of this specimen. However, an accumulation of macrophagelike cells could be observed at the putative rupture site. Comment Banked human fascial tissue has been available for decades and has been widely used in neurologic, orthopedic, ophthalmologic, cardiac, vascular, and general
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Fig 3. A, Suburethral sling graft 5 weeks after implantation. B, Adipose cells at allograft periphery 5 weeks after implantation. C, Sacrocolpopexy graft 7 months after implantation. Central graft shows linear orientation of connective tissue and fibrocytes. D, Sacrocolpopexy graft 7 months after implantation. Lateral graft shows acellular degenerated areas. E, Sacrocolpopexy graft 1 year after implantation. Portion of graft shown has linear orientation of connective tissue and fibrocytes. F, Sacrocolpopexy graft 1 year after implantation demonstrates immune cell accumulation. G, Sacrocolpopexy graft 17 months after implantation. H, Sacrocolpopexy graft 19 months after implantation shows probable site of graft rupture. (A-C, E-G: Hematoxylin and eosin. Original magnification ×100. D, H: Hematoxylin and eosin. Original magnification ×25. )
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surgical applications. Except in the case of cardiac valve replacement, such fascial grafts have performed well and durably.2-5 Theoretically, there is a risk of disease transmission from donor to host, but no such event has been documented with the use of fascial grafts. The use of biologic grafts is attractive mainly because of the known disadvantages associated with the use of synthetic grafts,6 such as graft erosion and rejection. Autologous fascia lata graft or rectus fascial tissue has been used in suburethral sling procedures for almost 100 years. Although this is an excellent sling material, the harvesting of autologous tissue is associated with some increase in patient discomfort and morbidity, along with increased operating time.7 Tissue bank grafts differ according to the steps used in their processing. After harvesting under aseptic conditions, the grafts must be preserved and may undergo sterilization. Preservation is either by deep-freezing (at –70°C) or by freeze-drying (lyophilization). Gamma irradiation is the most widely used process for sterilization and has been used for years to sterilize substances with possible bacterial contamination. However, it may have a negative impact on the integrity of the connective tissue macromolecules.8 The use of donor fascial grafts for urogynecologic procedures has become popular at some centers in North America during the last 5 years. There are currently no published data concerning surgical outcomes with the use of donor fascial grafts in sacrocolpopexy procedures. There is also limited published experience with the use of donor fascia lata grafts for suburethral sling procedures.7, 9, 10 In our center clinical failure occurred earlier with the use of small donor fascia grafts for suburethral sling placement (1 week to 4 months after the operation). Sacrocolpopexy graft failure became apparent 7 to 11 months after the initial operation. Fascial graft remnants were also more likely to be evident during reoperations for failed sacrocolpopexy. The difference in ability to retrieve graft remnants at the time of reoperation may be explained by the relative sizes of suburethral sling and sacrocolpopexy grafts. The average suburethral sling graft measures approximately 3 × 10 cm. The average sacrocolpopexy graft consists of 2 larger grafts, for example, 6 × 8 cm and 6 × 16 cm. Many of the grafts contain several areas with distinctive appearances. Some areas of the graft are remodeled to form tissue with linear organization, relatively low cellularity, and low vascularity. Such tissue appears similar to native fascia and might be expected to have high tensile strength. Other areas within the same grafts demonstrate a lack of linear organization and resemble noninflammatory scar tissue. Areas of total tissue breakdown are also evident, usually in areas of low cellularity or acellularity. Finally, a feature found in some but not all grafts was the
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presence of a host immune reaction to the graft, as indicated by the accumulation of white blood cell populations inside the graft. The process of biologic incorporation of the tendon allografts has been well described in the case of anterior cruciate ligament reconstruction.11, 12 In those allografts there is initial donor fibrocyte death, which is followed by neovascularization of the graft. Fibroblast migration into the implant is then followed by remodeling and eventual maturation of the graft. The histopathologic appearances of the grafts that we retrieved may be explained by several phenomena well known in orthopedic surgery: 1. When placed under stress, fibroblasts will remodel and lay down connective tissue in accordance with the direction of stress.13 For example, the midportions of the 2 sacrocolpopexy grafts that remained in situ appear to have successfully remodeled into fascialike tissue. This is consistent with the main stress of the sacrocolpopexy being transmitted down the center of the graft from the sacrum to the vagina. The eventual strength of a remodeled fascial graft located at the urethrovesical junction or within the peritoneal cavity is unknown. Whether the remodeled graft will withstand unusual forces, such as extremely heavy lifting, is also unknown. 2. Connective tissue under no stress can undergo degeneration and resorption14; for example, ligaments under minimal stress become weaker.15, 16 Areas of the sacrocolpopexy graft that are under relatively low levels of stress may remodel to form viable tissue with little linear orientation, whereas those areas under no stress at all may degenerate and be resorbed. 3. Animal studies suggest that the fascia and tendon grafts used for anterior cruciate ligament reconstruction can undergo a process of degeneration before becoming repopulated by host fibroblasts and blood vessels. The graft thus has an initial period of decreased strength before it eventually matures into tendonlike tissue.17, 18 4. The fascial allograft is antigenic. This fact is well documented in the orthopedic literature.19 The graft antigenicity is thought to be caused by the cellular elements, because collagen itself is probably not significantly antigenic.20 The antigenicity of fascial grafts is lessened by either deep-freezing or freeze-drying, but it does persist at a low level even in this relatively cell-poor tissue. Immune reaction of the host to the donor allograft has rarely been a clinical problem, but cases of graft rejection have been reported.21 Serologic evidence of immune reaction has been reported even in the absence of evidence of immune accumulations at
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the level of the implant.22 Animal studies document the disappearance of all donor cells within 4 weeks after implantation.23-25 5. Irradiation of fascial grafts may be associated with a decrease in graft strength. There is a dose-dependent deterioration in the in vitro mechanical properties of both tendon and bone-tendon-bone allografts.11, 26 The in vivo significance of this phenomenon is unknown, however, and irradiated allografts continue to be used. Until an animal study directly evaluates this variable, the effect of tissue irradiation remains speculative. The ultimate fate of a graft may depend on the rate at which remodeling, daily wear and tear, and immune forces compete. Ideal remodeling of implanted fascial grafts could be possible if the graft is of low antigenicity, the tissue can be quickly remodeled, and extreme stresses on the graft are avoided until the tissue has been remodeled. In contrast, it might be anticipated that a graft would fail if the graft itself were particularly antigenic, if the host tissues were unable to repopulate and revascularize the graft, or if extreme levels of stress were placed on the graft. Certain clinical conditions, such as diabetes mellitus with angiopathy or connective tissue disorders, might also interfere with successful graft remodeling. Again, there are few clinical data available to substantiate this hypothesis. On the basis of our experience we must recommend that the use of freeze-dried irradiated fascia lata grafts for suburethral slings or sacrocolpopexy procedures be avoided. To answer the important question of whether allografts prepared and implanted differently might be suitable for these procedures, an animal model is urgently needed. REFERENCES
1. Brubaker L. Suburethral sling procedures. Operative Tech Gynecol Surg 1997;2:44-50. 2. Pritchard JC, Drez D Jr, Moss M, Heck S. Long-term followup of anterior cruciate ligament reconstructions using freeze-dried fascia lata allografts. Am J Sports Med 1995;23:593-6. 3. Beyer CK, Albert DM. The use and fate of fascia lata and sclera in ophthalmic plastic and reconstructive surgery. Ophthalmology 1981;88:869-86. 4. Perkins R. Grafting materials and methods in reconstructive ear surgery. Ann Otol 1975;84:518-26. 5. Silver MD, Hudson RE, Trimble AS. Morphologic observations on heart valve prostheses made of fascia lata. J Thorac Cardiovasc Surg 1975;70:360-6. 6. Iglesia CB, Fenner DE, Brubaker L. The use of mesh in gynecologic surgery. Int Urogynecol J 1997;8:105-15. 7. Labasky RF, Soper T. Reduction of patient morbidity and cost using frozen cadaveric fascia lata for the pubovaginal sling [abstract 1794]. J Urol 1997;157:459A. 8. Bailey AJ. Irradiation-induced changes in the denaturation temperature and intermolecular cross-linking of tropocollagen. Radiat Res 1967;31:206-14. 9. Handa VL, Jensen JK, Germain MM, Ostergard DR. Banked human fascia lata for the suburethral sling procedure: a preliminary report. Obstet Gynecol 1996;88:1045-9.
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10. Wright EJ, Iselin CE, Carr LK, Webster GD. Pubovaginal sling using cadaveric allograft fascia for the treatment of intrinsic sphincter deficiency. J Urol 1998;160:759-62. 11. Horstman JK, Ahmadu-Suka F, Norrdin RW. Anterior cruciate ligament fascia lata allograft reconstruction: progressive histologic changes toward maturity. Arthroscopy 1993;9:509-18. 12. Shino K, Inoue M, Horibe S, Nagano J, Ong K. Maturation of allograft tendons transplanted into the knee: n arthroscopic and histological study. J Bone Joint Surg [Br] 1988;70:556-60. 13. Stearns ML. Studies on the development of connective tissue in transparent chambers in the rabbit’s ear. I. Am J Anat 1940;66:133-76. 14. Andrish JT, Woods LD. Dacron augmentation in anterior cruciate ligament reconstruction in dogs. Clin Orthop 1984;183:298302. 15. Amiel D, Woo SL, Harwood FL, Akeson WH. The effect of immobilization on collagen turnover in connective tissue: a biochemical-biomechanical correlation. Acta Orthop Scand 1982;53:325-32. 16. Loitz BJ, Zernicke RF, Vailas AC, Kody MH, Meals RA. Effects of short-term immobilization versus continuous passive motion on the biomechanical and biochemical properties of the rabbit tendon. Clin Orthop 1989;244:265-71. 17. Arnoczky SP, Warren RF, Ashlock MA. Replacement of the anterior cruciate ligament using a patellar tendon allograft: an experimental study. J Bone Joint Surg [Am] 1986;68:376-85. 18. Holden JP, Grood ES, Butler DL, Noyes FR, Mendenhall HV, Van Kampen CL, et al. Biomechanics of fascia lata ligament replacements: early postoperative changes in the goat. J Orthop Res 1988;6:639-47. 19. Rodrigo JJ, Jackson DW, Simon TM, Muto KN. The immune response to freeze-dried bone-tendon-bone ACL allografts in humans. Am J Knee Surg 1993;6:47-53. 20. Minami A, Ishii S, Ogino T, Oikawa T, Kobayashi H. Effect of the immunological antigenicity of the allogeneic tendons on tendon grafting. Hand 1984;14:111-9. 21. Pinkowski JL, Reiman PR, Chen SL. Human lymphocyte reaction to freeze-dried allograft and xenograft ligamentous tissue. Am J Sports Med 1989;17:595-600. 22. Thorson E, Rodrigo JJ, Vasseur P, Sharkey N, Heitter D. Replacement of the anterior cruciate ligament: a comparison of autografts and allografts in dogs. Acta Orthop Scand 1989;60:555-60. 23. Crawford JS. Nature of fascia lata and its fate after implantation. Am J Ophthalmol 1969;67:900-7. 24. Jackson DW, Simon TM, Kurzweil PR, Rosen MA. Survival of cells after intra-articular transplantation of fresh allografts of the patellar and anterior cruciate ligaments. DNA-probe analysis in a goat model. J Bone Joint Surg [Am] 1992;74:112-8. 25. Kleiner JB, Amiel D, Roux, Akeson WH. Origin of replacement cells for the anterior cruciate ligament autograft. J Orthop Res 1986;4:466-74. 26. De Deyne P, Haut RC. Some effects of gamma irradiation on patellar tendon allografts. Connect Tissue Res 1991;27:51-62.
Discussion DR JOHN R. MIKLOS, Atlanta, Georgia. Historically, pubovaginal sling and abdominal sacrocolpopexy procedures have been shown to be durable operations for the long-term cure of stress urinary incontinence and vaginal vault prolapse, respectively. Until recently, these procedures used either harvested autologous fascial grafts or synthetic materials. Unfortunately, harvesting rectus fascia or fascia lata requires additional operations and incurs risks, including hematoma, infection, herniation, and patient discomfort. In an effort to reduce these risks, synthetic materials such as silicone, polypropylene, polytetrafluoroethylene, and polyester are often used as alter-
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natives to autologous fascial grafts. However, these synthetic materials have been associated with increased rates of infection, graft erosion, and foreign-body reaction when compared with autologous fascial graft. In an attempt to minimize operating room time, postoperative pain, and the morbidity associated with both autologous fascial grafts and synthetic materials, fascia lata allografts have recently been adapted for use in reconstructive pelvic operations. FitzGerald et al have reported their experience with cadaveric fascial grafts in 102 patients undergoing reconstructive pelvic operations. Sixty-seven patients underwent sacrocolpopexy and 35 patients underwent a suburethral sling procedure. They reported 6 surgical failures necessitating reoperation in each group. Reoperation in these 12 patients resulted in identification of graft remnants in 7 patients, 5 in the sacrocolpopexy group and 2 in the sling group. The operative findings and histologic evaluations of these 7 patients constituted the framework, conclusions, and recommendations set forth by this article. As summarized in the abstract, “Histopathologic analyses of the retrieved material demonstrated several ongoing processes in the failed grafts. A few grafts showed areas of ideal remodeling. Most grafts, however, showed areas of disorganized remodeling and areas of graft degeneration. Evidence of immune reaction to the graft was observed in some cases.” Especially interesting were the operative and histologic findings in 2 of the 5 failed sacrocolpopexy procedures. Two patients were found to have intact fascial grafts between the sacrum and the vagina. The subjective assessment of FitzGerald et al was that the grafts appeared lax and attenuated. It was in these 2 patients that the histologic examination showed areas of ideal remodeling and overall graft viability. One can conclude from the histologic results described that there is inconsistent graft response among surgical failures. The increasing use of cadaveric allografts in reconstructive pelvic surgery makes this article an important contribution to the surgical literature. However, the strength of this study is limited by (1) small sample size and (2) inconsistent histologic graft response among the surgical failures. I have several questions for the authors: 1. What objective parameters were used to evaluate urinary incontinence and vaginal prolapse preoperatively and postoperatively? 2. In the 2 patients with failed sacrocolpopexy procedures who had intact fascial grafts with histologic viability, would objective preoperative and postoperative measurements of graft length have been beneficial, instead of a subjective assessment that the graft appeared attenuated? Is it possible that the graft was not stretched but rather that a vaginal stretching was responsible for the failure? I have personally seen sacrocolpopexy failures that occurred even though an intact synthetic mesh was still attached to the sacrum and the vaginal apex.
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3. You had a reoperative rate of 12% among your 102 patients. Were this reoperative rate and the failure rate the same? If the failure rate and the reoperative rate were not the same, what were the failure rates for slings and sacrocolpopexy? If the reoperative and failure rates were the same, then you have surgical cure rates of 83% for slings and 92% for sacrocolpopexy. 4. If the allograft causes unacceptable failures, how do you account for these apparent cure rates, which are consistent with the acceptable cure rates for these operations with autologous fascial grafts and synthetic grafts? 5. The sacrocolpopexy technique described has the allogenic fascia at raw surfaces at the sacrum and the vagina, but the midportion remains above the peritoneum. You have admitted to harvesting your grafts consistently at the points of attachment and not at the midportion, which seems to have degenerated. Do you not think that it is necessary to place the fascia against a raw surface (retroperitoneal) as is routinely performed in standard abdominal sacrocolpopexy? Would the fascia not have a better chance of fibrosis or adhesions against the vascular sacrum and presacral space? 6. Does a specific type of histologic appearance of the fascial graft remnant correlate with fascial anatomic strength and function? 7. Would not a comparison study be the most scientific way of determining correlation between graft remnant degeneration and surgical failure? Specifically, should not one compare graft remnants of successful surgical procedures with those of surgical failures? Is it not possible for surgically cured patients to have histologic findings of a degenerating graft? 8. You have recommended avoiding the use of all freeze-dried irradiated fascia lata grafts for suburethral slings and sacrocolpopexies. Are these recommendations all-encompassing to include all allogenic fascial grafts, independent of the processes of radiation, sterilization, and preservation? Not all allogenic fascial grafts are prepared in the same way. It is well known that the amount of radiation and the type of sterilization may have an effect on the strength and longevity of cadaveric fascial tissues. Despite the findings and recommendations set forth in this article, I leave the Society with 2 thoughts: 1. Wright et al from Duke University wrote a 1998 article that was referenced by FitzGerald et al (see reference 10 of article). In a comparison study of 92 patients with allograft and autograft pubovaginal slings there was no significant difference in the cure rate of stress incontinence, and the operative time was shortened by use of the allograft. 2. This article notes apparent cure rates of 83% for
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slings and 92% for sacrocolpopexies, rates that are consistent with the international literature for these procedures with either autologous or synthetic materials. In conclusion, I believe that this article is an important contribution to our growing knowledge regarding the use of donor allografts in gynecologic surgery but is limited in its clinical applicability because of its small sample size, inconsistent graft responses, and lack of comparison studies. I commend and encourage FitzGerald et al to continue with this area of research. Although their initial observations may dissuade us from further use of such materials, I believe that we as reconstructive surgeons searching for better procedures and better materials should keep an open mind and use this pilot study only as a springboard for further research. DR FITZGERALD (Closing). Our reoperative rate was not the same as our failure rate. We did have some other failures; these were simply the ones that we could prove
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were caused by a materials problem. You asked how we know that it was a materials factor and not a technical factor or patient factor. We know only because we had the opportunity to reoperate. The failure was not subtle; the grafts were broken or gone, so there was at least a materials problem present. I think that this is of significant clinical importance, because if someone tried to sell a material for sacrocolpopexy that had a disappearance rate of ≥12% (and this is an evolving situation; it is now a 17% failure or disappearance rate) I do not think that we would use it for our procedures. You asked whether we think that it is necessary to cover the graft with peritoneum, and we did not do so. It is not known whether this is necessary. The experimental and clinical literature from work on anterior cruciate ligament replacement in orthopedic surgery suggests that the grafts neovascularize from the ends, but it is not known whether the outcome would be improved if we covered it with peritoneum. That is an interesting point.
Key words: Donor tissue, fascia lata, graft failure
Tissue bank fascia lata allografts are used in surgical procedures for pelvic reconstruction and genuine stress urinary incontinence. The longevity and the histologic fate of this material appear to be responsible for certain surgical failures. We reoperated on 12 patients. Our findings in these 12 cases form the basis of this report and offer insight into why such grafts might fail. Material and methods Patients. Twelve patients with previous irradiated and freeze-dried donor fascia lata graft implants have undergone reoperation at our center. Their charts and any available histologic data were reviewed. Donor fascia lata allograft processing. The donor fascia lata allografts under discussion were obtained from a tissue bank accredited by the American Association of Tissue Banks. Our supplier reports no previous notification of any clinical problems with the use of their fascia lata grafts in urogynecologic procedures and reports good success with the use of their fascia lata grafts in orthopedic procedures. All tissues were harvested from human cadavers with aseptic technique. The tissue was then preserved and perhaps underwent additional sterilization.
From the Division of Urogynecology and Reconstructive Pelvic Surgery,a the Department of Biochemistry,b and the Department of Pathology,c Rush–Presbyterian–St Luke’s Medical Center. Presented at the Twenty-fifth Scientific Meeting of the Society of Gynecologic Surgeons, San Diego, California, February 19-21, 1999. Reprints not available from the authors. Copyright © 1999 by Mosby, Inc. 0002-9378/99 $8.00 + 0 6/6/103117
Freeze-dried irradiated fascia lata grafts were prepared as follows: (1) A medical and social history was obtained from the donor’s next of kin. Donors with known risk factors for human immunodeficiency virus infection and hepatitis were excluded. (2) All tissues were retrieved under aseptic conditions and soaked in antibiotic solution. (3) Microbiologic cultures were obtained from tissues at the time of harvest, and serologic screens for human immunodeficiency virus, hepatitis B and C viruses, and human T-lymphotropic virus type 1 were performed, as was a rapid plasma reagin test. Any positive serologic test result led to exclusion of the donor. (4) Fascia lata grafts were freeze-dried and packaged. (5) Fascia lata grafts were terminally sterilized with 2.5 Mrad gamma irradiation. Surgical technique. Before implantation, the donor graft was soaked in sodium chloride solution for 20 minutes. Donor fascial grafts were used to construct suburethral slings without the need to harvest autologous rectus fascial tissue, as previously described.1 We used a sling of intermediate length (approximately 3 × 10 cm) that was attached to rectus fascial tissue with polytetrafluoroethylene (GORE-TEX; W.L. Gore & Associates, Inc, Flagstaff, Ariz) suture arms. When performing a sacrocolpopexy, we placed 2 or 3 polytetrafluoroethylene sutures into the anterior longitudinal ligament of sacrum at the level of S2 or S3. The peritoneum was opened over both the anterior vagina and the posterior vagina. Large pieces of fascial tissue (eg, 6 × 16 cm) were placed on the anterior and posterior vagina with polytetrafluoroethylene suture to form a Y-shaped graft. The peritoneum was not routinely 1339
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Fig 1. Gross appearance of attenuated sacrocolpopexy graft 12 months after implantation.
closed over the implant. Concomitant urogynecologic procedures were undertaken as indicated. All patients received perioperative intravenous antibiotic therapy (eg, 2 g cefoxitin intravenously every 8 hours for 24-72 hours). All patients were asked to observe postoperative restrictions, including avoidance of lifting >5 lb in weight and avoidance of placing anything in the vagina for 12 weeks. Reoperation and retrieval of graft remnants. At the time of reoperation for failure of the initial surgical intervention, any visible graft remnant was removed or sampled for pathologic evaluation. A reoperative surgical procedure without the use of donor fascia lata grafts was then performed as indicated. Any retrieved graft specimens were placed in 10% buffered formaldehyde solution and processed for paraffin embedding according to standard protocols. Serial longitudinal sections 4 µm in thickness were cut. Hematoxylin and eosin staining was performed. Results Clinical characteristics. We have used fascia lata allografts in 67 sacrocolpopexy procedures and 35 suburethral sling procedures. We have reoperated on 13 of those patients because of recurrence or persistence of the patient’s symptoms. As outlined in Table I, 6 patients with donor fascia lata graft slings and 6 patients with donor fascia sacrocolpopexy grafts underwent reoperation. Those 12 patients represent 12% of the total population of patients who had allografts placed. Almost all the patients in whom suburethral sling procedures were performed had initial subjective cure of their symptoms of stress urinary incontinence. Only the first patient listed in Table I had immediate return of her symptoms once the catheter was removed 1 week after the operation. In the other cases the symptom-free period lasted between 6 and 16 weeks.
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All patients who received sacrocolpopexy grafts had initial subjective cure of the symptoms of pelvic organ prolapse. This cure was objectively documented 3 months after the operation for all patients in the standing, straining position. The patients went on to have recurrence of symptoms between 7 and 11 months after the initial operation, and examination confirmed recurrent prolapse in all cases. Findings at reoperation. Reoperation occurred as early as 5 weeks after the initial procedure. We were able to retrieve graft remnants from a total of 7 patients. When we could not find any graft remnants, we were still always able to identify the former graft site by recovering intact suture knots that enclosed no tissue. Such suture knots were easily identifiable on the anterior longitudinal ligament of the sacrum. Graft remnants were retrieved in all but 1 case during reoperation after failed sacrocolpopexy. In 2 cases sacrocolpopexy grafts still linked the vaginal apex to the sacrum, although the patient clinically had recurrence of pelvic organ prolapse. These in situ grafts were narrow, attenuated, and lax, as illustrated in Fig 1. In other cases in which no graft remained between the vagina and the sacrum, large amounts of graft remnant could usually be identified on reopening of the peritoneum overlying the posterior vagina. Histopathologic characteristics. Fig 2, A, illustrates the microscopic appearance of a donor graft once it has been reconstituted in sodium chloride solution before implantation. The connective tissue forms an open array, with gaps between the connective tissue fibers. Donor fibrocyte nuclei are visible, but the overall cellular content of the graft is low. Fig 2, B, demonstrates the loose connective tissue that is attached to the allografts in some areas. These areas are more cellular. This cross-section of the graft also illustrates the spaces between the graft fibers that are present after processing. Fig 3, A, illustrates the microscopic appearance of a suburethral sling graft retrieved after 5 weeks. The cellularity is high, with host fibroblast proliferation and graft neovascularization. There is little evidence of remodeling into tissue resembling fascia or tendon. Instead, the graft tissue has reorganized to resemble noninflammatory scar tissue, with little linear orientation of fibroblasts or connective tissue. Some small areas of the graft demonstrate less cellularity and exhibit tissue degeneration. Fig 3, B, illustrates fat cells still present in the graft. Fig 3, C, illustrates the microscopic appearance of a sacrocolpopexy graft retrieved 7 months after implantation. At reoperation a narrow attenuated graft remained in place between the sacrum and the vagina. Away from the graft periphery there is evidence of some of the desired remodeling of the graft into a unit capable of withstanding stress. This area appears viable, with a linear orientation of fibrocytes cells within connective tissue. Other areas demonstrate high cellularity but have not re-
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Fig 2. Reconstituted donor fascia lata graft before implantation. A, Open connective tissue array. B, Loose connective tissue attached to graft. (A-B, Hematoxylin and eosin. Original magnification ×100.)
Table I. Initial surgical procedure at which donor graft was implanted, time to reoperation for initial surgical failure, and findings at reoperation Patient No.
Initial surgical procedure
Time to symptom recurrence
Time to reoperation
1 2 3 4 5 6 7
Suburethral sling Suburethral sling Suburethral sling Suburethral sling Suburethral sling Suburethral sling Sacrocolpopexy
1 wk 6 wk 4 mo 6 wk 3 mo 5 mo 6 mo
5 wk 3 mo 6 mo 9 mo 9 mo 6 mo 6 mo
8 9 10 11
Sacrocolpopexy Sacrocolpopexy Sacrocolpopexy Sacrocolpopexy
7 mo 9 mo 11 mo 9 mo
7 mo 12 mo 12 mo 17 mo
12
Sacrocolpopexy
7 mo
19 mo
Gross findings at reoperation
Softened fragmented graft in retropubic tunnels No graft remnants No graft remnants Softened fragmented graft pieces in bilateral retropubic tunnels No graft remnants No graft remnants Graft adherent to both sacrum and vagina but without graft in between Attenuated narrow graft in place No graft remnants Attenuated narrow graft in place No graft between vagina and sacrum but portions of graft on posterior vagina Graft portions at vaginal apex, on posterior vagina, and on sacrum
modeled in a linear fashion, yielding microscopic appearances similar to the scarlike tissue seen in Fig 2, A. Finally, other areas demonstrate widespread breakdown of the tissue architecture (Fig 3, D). Fig 3, E, illustrates microscopic findings of a sacrocolpopexy graft on retrieval after 1 year. At the time of reoperation a narrow attenuated sacrocolpopexy graft was found to be in situ between the posterior vagina and the anterior longitudinal ligament of the sacrum. On microscopic examination the graft can be seen to exhibit high cellularity and vascularity. The connective tissue is longitudinally aligned in many areas in a manner that might be predicted to be ideal although with atypically high cellularity. However, other, smaller areas demonstrate less organization. There is a significant level of white blood cell accumulation throughout the graft (Fig 3, F). Overall this graft appears to be viable, consistent with its persistence at the implanted location. The microscopic appearance of a graft retrieved from the posterior vaginal wall after 17 months is illustrated in
Fig No. 3, A and B
3, D 2 and 3, E 3, G 3, H
Fig 3, G. Overall the graft has high cellularity and vascularity. The structure of the graft is haphazard. This tissue would be expected to have low tensile strength because of its high vascularity. There is little evidence of immune response to the graft in this case. Fig 3, H, illustrates the specific site of probable graft rupture. This was a sacrocolpopexy graft retrieved 19 months after implantation. One extreme of the graft demonstrates a clear transition from an ideal type of remodeling through a short area of open connective tissue to the end of the graft, the point at which we presume the graft ruptured. Except at suture sites a host immune response to the graft is not a feature of this specimen. However, an accumulation of macrophagelike cells could be observed at the putative rupture site. Comment Banked human fascial tissue has been available for decades and has been widely used in neurologic, orthopedic, ophthalmologic, cardiac, vascular, and general
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Fig 3. A, Suburethral sling graft 5 weeks after implantation. B, Adipose cells at allograft periphery 5 weeks after implantation. C, Sacrocolpopexy graft 7 months after implantation. Central graft shows linear orientation of connective tissue and fibrocytes. D, Sacrocolpopexy graft 7 months after implantation. Lateral graft shows acellular degenerated areas. E, Sacrocolpopexy graft 1 year after implantation. Portion of graft shown has linear orientation of connective tissue and fibrocytes. F, Sacrocolpopexy graft 1 year after implantation demonstrates immune cell accumulation. G, Sacrocolpopexy graft 17 months after implantation. H, Sacrocolpopexy graft 19 months after implantation shows probable site of graft rupture. (A-C, E-G: Hematoxylin and eosin. Original magnification ×100. D, H: Hematoxylin and eosin. Original magnification ×25. )
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surgical applications. Except in the case of cardiac valve replacement, such fascial grafts have performed well and durably.2-5 Theoretically, there is a risk of disease transmission from donor to host, but no such event has been documented with the use of fascial grafts. The use of biologic grafts is attractive mainly because of the known disadvantages associated with the use of synthetic grafts,6 such as graft erosion and rejection. Autologous fascia lata graft or rectus fascial tissue has been used in suburethral sling procedures for almost 100 years. Although this is an excellent sling material, the harvesting of autologous tissue is associated with some increase in patient discomfort and morbidity, along with increased operating time.7 Tissue bank grafts differ according to the steps used in their processing. After harvesting under aseptic conditions, the grafts must be preserved and may undergo sterilization. Preservation is either by deep-freezing (at –70°C) or by freeze-drying (lyophilization). Gamma irradiation is the most widely used process for sterilization and has been used for years to sterilize substances with possible bacterial contamination. However, it may have a negative impact on the integrity of the connective tissue macromolecules.8 The use of donor fascial grafts for urogynecologic procedures has become popular at some centers in North America during the last 5 years. There are currently no published data concerning surgical outcomes with the use of donor fascial grafts in sacrocolpopexy procedures. There is also limited published experience with the use of donor fascia lata grafts for suburethral sling procedures.7, 9, 10 In our center clinical failure occurred earlier with the use of small donor fascia grafts for suburethral sling placement (1 week to 4 months after the operation). Sacrocolpopexy graft failure became apparent 7 to 11 months after the initial operation. Fascial graft remnants were also more likely to be evident during reoperations for failed sacrocolpopexy. The difference in ability to retrieve graft remnants at the time of reoperation may be explained by the relative sizes of suburethral sling and sacrocolpopexy grafts. The average suburethral sling graft measures approximately 3 × 10 cm. The average sacrocolpopexy graft consists of 2 larger grafts, for example, 6 × 8 cm and 6 × 16 cm. Many of the grafts contain several areas with distinctive appearances. Some areas of the graft are remodeled to form tissue with linear organization, relatively low cellularity, and low vascularity. Such tissue appears similar to native fascia and might be expected to have high tensile strength. Other areas within the same grafts demonstrate a lack of linear organization and resemble noninflammatory scar tissue. Areas of total tissue breakdown are also evident, usually in areas of low cellularity or acellularity. Finally, a feature found in some but not all grafts was the
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presence of a host immune reaction to the graft, as indicated by the accumulation of white blood cell populations inside the graft. The process of biologic incorporation of the tendon allografts has been well described in the case of anterior cruciate ligament reconstruction.11, 12 In those allografts there is initial donor fibrocyte death, which is followed by neovascularization of the graft. Fibroblast migration into the implant is then followed by remodeling and eventual maturation of the graft. The histopathologic appearances of the grafts that we retrieved may be explained by several phenomena well known in orthopedic surgery: 1. When placed under stress, fibroblasts will remodel and lay down connective tissue in accordance with the direction of stress.13 For example, the midportions of the 2 sacrocolpopexy grafts that remained in situ appear to have successfully remodeled into fascialike tissue. This is consistent with the main stress of the sacrocolpopexy being transmitted down the center of the graft from the sacrum to the vagina. The eventual strength of a remodeled fascial graft located at the urethrovesical junction or within the peritoneal cavity is unknown. Whether the remodeled graft will withstand unusual forces, such as extremely heavy lifting, is also unknown. 2. Connective tissue under no stress can undergo degeneration and resorption14; for example, ligaments under minimal stress become weaker.15, 16 Areas of the sacrocolpopexy graft that are under relatively low levels of stress may remodel to form viable tissue with little linear orientation, whereas those areas under no stress at all may degenerate and be resorbed. 3. Animal studies suggest that the fascia and tendon grafts used for anterior cruciate ligament reconstruction can undergo a process of degeneration before becoming repopulated by host fibroblasts and blood vessels. The graft thus has an initial period of decreased strength before it eventually matures into tendonlike tissue.17, 18 4. The fascial allograft is antigenic. This fact is well documented in the orthopedic literature.19 The graft antigenicity is thought to be caused by the cellular elements, because collagen itself is probably not significantly antigenic.20 The antigenicity of fascial grafts is lessened by either deep-freezing or freeze-drying, but it does persist at a low level even in this relatively cell-poor tissue. Immune reaction of the host to the donor allograft has rarely been a clinical problem, but cases of graft rejection have been reported.21 Serologic evidence of immune reaction has been reported even in the absence of evidence of immune accumulations at
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the level of the implant.22 Animal studies document the disappearance of all donor cells within 4 weeks after implantation.23-25 5. Irradiation of fascial grafts may be associated with a decrease in graft strength. There is a dose-dependent deterioration in the in vitro mechanical properties of both tendon and bone-tendon-bone allografts.11, 26 The in vivo significance of this phenomenon is unknown, however, and irradiated allografts continue to be used. Until an animal study directly evaluates this variable, the effect of tissue irradiation remains speculative. The ultimate fate of a graft may depend on the rate at which remodeling, daily wear and tear, and immune forces compete. Ideal remodeling of implanted fascial grafts could be possible if the graft is of low antigenicity, the tissue can be quickly remodeled, and extreme stresses on the graft are avoided until the tissue has been remodeled. In contrast, it might be anticipated that a graft would fail if the graft itself were particularly antigenic, if the host tissues were unable to repopulate and revascularize the graft, or if extreme levels of stress were placed on the graft. Certain clinical conditions, such as diabetes mellitus with angiopathy or connective tissue disorders, might also interfere with successful graft remodeling. Again, there are few clinical data available to substantiate this hypothesis. On the basis of our experience we must recommend that the use of freeze-dried irradiated fascia lata grafts for suburethral slings or sacrocolpopexy procedures be avoided. To answer the important question of whether allografts prepared and implanted differently might be suitable for these procedures, an animal model is urgently needed. REFERENCES
1. Brubaker L. Suburethral sling procedures. Operative Tech Gynecol Surg 1997;2:44-50. 2. Pritchard JC, Drez D Jr, Moss M, Heck S. Long-term followup of anterior cruciate ligament reconstructions using freeze-dried fascia lata allografts. Am J Sports Med 1995;23:593-6. 3. Beyer CK, Albert DM. The use and fate of fascia lata and sclera in ophthalmic plastic and reconstructive surgery. Ophthalmology 1981;88:869-86. 4. Perkins R. Grafting materials and methods in reconstructive ear surgery. Ann Otol 1975;84:518-26. 5. Silver MD, Hudson RE, Trimble AS. Morphologic observations on heart valve prostheses made of fascia lata. J Thorac Cardiovasc Surg 1975;70:360-6. 6. Iglesia CB, Fenner DE, Brubaker L. The use of mesh in gynecologic surgery. Int Urogynecol J 1997;8:105-15. 7. Labasky RF, Soper T. Reduction of patient morbidity and cost using frozen cadaveric fascia lata for the pubovaginal sling [abstract 1794]. J Urol 1997;157:459A. 8. Bailey AJ. Irradiation-induced changes in the denaturation temperature and intermolecular cross-linking of tropocollagen. Radiat Res 1967;31:206-14. 9. Handa VL, Jensen JK, Germain MM, Ostergard DR. Banked human fascia lata for the suburethral sling procedure: a preliminary report. Obstet Gynecol 1996;88:1045-9.
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10. Wright EJ, Iselin CE, Carr LK, Webster GD. Pubovaginal sling using cadaveric allograft fascia for the treatment of intrinsic sphincter deficiency. J Urol 1998;160:759-62. 11. Horstman JK, Ahmadu-Suka F, Norrdin RW. Anterior cruciate ligament fascia lata allograft reconstruction: progressive histologic changes toward maturity. Arthroscopy 1993;9:509-18. 12. Shino K, Inoue M, Horibe S, Nagano J, Ong K. Maturation of allograft tendons transplanted into the knee: n arthroscopic and histological study. J Bone Joint Surg [Br] 1988;70:556-60. 13. Stearns ML. Studies on the development of connective tissue in transparent chambers in the rabbit’s ear. I. Am J Anat 1940;66:133-76. 14. Andrish JT, Woods LD. Dacron augmentation in anterior cruciate ligament reconstruction in dogs. Clin Orthop 1984;183:298302. 15. Amiel D, Woo SL, Harwood FL, Akeson WH. The effect of immobilization on collagen turnover in connective tissue: a biochemical-biomechanical correlation. Acta Orthop Scand 1982;53:325-32. 16. Loitz BJ, Zernicke RF, Vailas AC, Kody MH, Meals RA. Effects of short-term immobilization versus continuous passive motion on the biomechanical and biochemical properties of the rabbit tendon. Clin Orthop 1989;244:265-71. 17. Arnoczky SP, Warren RF, Ashlock MA. Replacement of the anterior cruciate ligament using a patellar tendon allograft: an experimental study. J Bone Joint Surg [Am] 1986;68:376-85. 18. Holden JP, Grood ES, Butler DL, Noyes FR, Mendenhall HV, Van Kampen CL, et al. Biomechanics of fascia lata ligament replacements: early postoperative changes in the goat. J Orthop Res 1988;6:639-47. 19. Rodrigo JJ, Jackson DW, Simon TM, Muto KN. The immune response to freeze-dried bone-tendon-bone ACL allografts in humans. Am J Knee Surg 1993;6:47-53. 20. Minami A, Ishii S, Ogino T, Oikawa T, Kobayashi H. Effect of the immunological antigenicity of the allogeneic tendons on tendon grafting. Hand 1984;14:111-9. 21. Pinkowski JL, Reiman PR, Chen SL. Human lymphocyte reaction to freeze-dried allograft and xenograft ligamentous tissue. Am J Sports Med 1989;17:595-600. 22. Thorson E, Rodrigo JJ, Vasseur P, Sharkey N, Heitter D. Replacement of the anterior cruciate ligament: a comparison of autografts and allografts in dogs. Acta Orthop Scand 1989;60:555-60. 23. Crawford JS. Nature of fascia lata and its fate after implantation. Am J Ophthalmol 1969;67:900-7. 24. Jackson DW, Simon TM, Kurzweil PR, Rosen MA. Survival of cells after intra-articular transplantation of fresh allografts of the patellar and anterior cruciate ligaments. DNA-probe analysis in a goat model. J Bone Joint Surg [Am] 1992;74:112-8. 25. Kleiner JB, Amiel D, Roux, Akeson WH. Origin of replacement cells for the anterior cruciate ligament autograft. J Orthop Res 1986;4:466-74. 26. De Deyne P, Haut RC. Some effects of gamma irradiation on patellar tendon allografts. Connect Tissue Res 1991;27:51-62.
Discussion DR JOHN R. MIKLOS, Atlanta, Georgia. Historically, pubovaginal sling and abdominal sacrocolpopexy procedures have been shown to be durable operations for the long-term cure of stress urinary incontinence and vaginal vault prolapse, respectively. Until recently, these procedures used either harvested autologous fascial grafts or synthetic materials. Unfortunately, harvesting rectus fascia or fascia lata requires additional operations and incurs risks, including hematoma, infection, herniation, and patient discomfort. In an effort to reduce these risks, synthetic materials such as silicone, polypropylene, polytetrafluoroethylene, and polyester are often used as alter-
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natives to autologous fascial grafts. However, these synthetic materials have been associated with increased rates of infection, graft erosion, and foreign-body reaction when compared with autologous fascial graft. In an attempt to minimize operating room time, postoperative pain, and the morbidity associated with both autologous fascial grafts and synthetic materials, fascia lata allografts have recently been adapted for use in reconstructive pelvic operations. FitzGerald et al have reported their experience with cadaveric fascial grafts in 102 patients undergoing reconstructive pelvic operations. Sixty-seven patients underwent sacrocolpopexy and 35 patients underwent a suburethral sling procedure. They reported 6 surgical failures necessitating reoperation in each group. Reoperation in these 12 patients resulted in identification of graft remnants in 7 patients, 5 in the sacrocolpopexy group and 2 in the sling group. The operative findings and histologic evaluations of these 7 patients constituted the framework, conclusions, and recommendations set forth by this article. As summarized in the abstract, “Histopathologic analyses of the retrieved material demonstrated several ongoing processes in the failed grafts. A few grafts showed areas of ideal remodeling. Most grafts, however, showed areas of disorganized remodeling and areas of graft degeneration. Evidence of immune reaction to the graft was observed in some cases.” Especially interesting were the operative and histologic findings in 2 of the 5 failed sacrocolpopexy procedures. Two patients were found to have intact fascial grafts between the sacrum and the vagina. The subjective assessment of FitzGerald et al was that the grafts appeared lax and attenuated. It was in these 2 patients that the histologic examination showed areas of ideal remodeling and overall graft viability. One can conclude from the histologic results described that there is inconsistent graft response among surgical failures. The increasing use of cadaveric allografts in reconstructive pelvic surgery makes this article an important contribution to the surgical literature. However, the strength of this study is limited by (1) small sample size and (2) inconsistent histologic graft response among the surgical failures. I have several questions for the authors: 1. What objective parameters were used to evaluate urinary incontinence and vaginal prolapse preoperatively and postoperatively? 2. In the 2 patients with failed sacrocolpopexy procedures who had intact fascial grafts with histologic viability, would objective preoperative and postoperative measurements of graft length have been beneficial, instead of a subjective assessment that the graft appeared attenuated? Is it possible that the graft was not stretched but rather that a vaginal stretching was responsible for the failure? I have personally seen sacrocolpopexy failures that occurred even though an intact synthetic mesh was still attached to the sacrum and the vaginal apex.
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3. You had a reoperative rate of 12% among your 102 patients. Were this reoperative rate and the failure rate the same? If the failure rate and the reoperative rate were not the same, what were the failure rates for slings and sacrocolpopexy? If the reoperative and failure rates were the same, then you have surgical cure rates of 83% for slings and 92% for sacrocolpopexy. 4. If the allograft causes unacceptable failures, how do you account for these apparent cure rates, which are consistent with the acceptable cure rates for these operations with autologous fascial grafts and synthetic grafts? 5. The sacrocolpopexy technique described has the allogenic fascia at raw surfaces at the sacrum and the vagina, but the midportion remains above the peritoneum. You have admitted to harvesting your grafts consistently at the points of attachment and not at the midportion, which seems to have degenerated. Do you not think that it is necessary to place the fascia against a raw surface (retroperitoneal) as is routinely performed in standard abdominal sacrocolpopexy? Would the fascia not have a better chance of fibrosis or adhesions against the vascular sacrum and presacral space? 6. Does a specific type of histologic appearance of the fascial graft remnant correlate with fascial anatomic strength and function? 7. Would not a comparison study be the most scientific way of determining correlation between graft remnant degeneration and surgical failure? Specifically, should not one compare graft remnants of successful surgical procedures with those of surgical failures? Is it not possible for surgically cured patients to have histologic findings of a degenerating graft? 8. You have recommended avoiding the use of all freeze-dried irradiated fascia lata grafts for suburethral slings and sacrocolpopexies. Are these recommendations all-encompassing to include all allogenic fascial grafts, independent of the processes of radiation, sterilization, and preservation? Not all allogenic fascial grafts are prepared in the same way. It is well known that the amount of radiation and the type of sterilization may have an effect on the strength and longevity of cadaveric fascial tissues. Despite the findings and recommendations set forth in this article, I leave the Society with 2 thoughts: 1. Wright et al from Duke University wrote a 1998 article that was referenced by FitzGerald et al (see reference 10 of article). In a comparison study of 92 patients with allograft and autograft pubovaginal slings there was no significant difference in the cure rate of stress incontinence, and the operative time was shortened by use of the allograft. 2. This article notes apparent cure rates of 83% for
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slings and 92% for sacrocolpopexies, rates that are consistent with the international literature for these procedures with either autologous or synthetic materials. In conclusion, I believe that this article is an important contribution to our growing knowledge regarding the use of donor allografts in gynecologic surgery but is limited in its clinical applicability because of its small sample size, inconsistent graft responses, and lack of comparison studies. I commend and encourage FitzGerald et al to continue with this area of research. Although their initial observations may dissuade us from further use of such materials, I believe that we as reconstructive surgeons searching for better procedures and better materials should keep an open mind and use this pilot study only as a springboard for further research. DR FITZGERALD (Closing). Our reoperative rate was not the same as our failure rate. We did have some other failures; these were simply the ones that we could prove
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were caused by a materials problem. You asked how we know that it was a materials factor and not a technical factor or patient factor. We know only because we had the opportunity to reoperate. The failure was not subtle; the grafts were broken or gone, so there was at least a materials problem present. I think that this is of significant clinical importance, because if someone tried to sell a material for sacrocolpopexy that had a disappearance rate of ≥12% (and this is an evolving situation; it is now a 17% failure or disappearance rate) I do not think that we would use it for our procedures. You asked whether we think that it is necessary to cover the graft with peritoneum, and we did not do so. It is not known whether this is necessary. The experimental and clinical literature from work on anterior cruciate ligament replacement in orthopedic surgery suggests that the grafts neovascularize from the ends, but it is not known whether the outcome would be improved if we covered it with peritoneum. That is an interesting point.