Review Article Synthetic Mesh in the Surgical Repair of Pelvic Organ Prolapse: Current Status and Future Directions Tristan Keys, Lysanne Campeau, and Gopal Badlani In light of the recent Food and Drug Administration public health notification regarding complications associated with transvaginally placed mesh for pelvic organ prolapse (POP) repair, we review recent literature to evaluate current outcomes and complication data, analyze the clinical need for mesh on the basis of genetic and biochemical etiologies of POP, and investigate trends of mesh use via an American Urological Association member survey. Mesh-based techniques show better anatomic results than traditional repair of anterior POP, but subjective outcomes are equivalent. Further research and Level I evidence are required before mesh-based repair of POP can be standardized. Adequate surgical training and patient selection should decrease complication rates. UROLOGY 80: 237–243, 2012. Published by Elsevier Inc.

A

pproaches to the surgical management of pelvic organ prolapse (POP) have undergone several paradigm shifts over the last few decades. Innovative technologies are being incorporated into treatment methodologies, specifically in the arena of surgical devices. Subsequently, there has been a concerted effort to improve surgical outcomes while keeping patient safety paramount. This, unfortunately, has led to significant controversy in the surgical treatment of POP. It was initially believed that synthetic mesh for augmented repair would provide an effective tool in the surgeon’s armamentarium against severe and/or recurrent disease. The advent of commercialized kits, however, has led to widespread use of mesh to treat incontinence and prolapse. Many believe their introduction into clinical use has been too rapid, and that sufficient clinical evidence to garner Food and Drug Administration (FDA) approval is lacking. The controversy surrounding the rise in reported complications associated with prolapse repair is evidenced by the FDA Safety Communication Update.1 To help gain insight into current trends of synthetic polypropylene mesh use for POP repair, we review the most recent literature regarding efficacy of mesh-based repairs in randomized controlled trials (RCTs), genetic and biochemical factors supporting its use in stress urinary incontinence (SUI)/POP repair, and complications associated with mesh use, differentiating between com-

Financial Disclosure: The authors declare that they have no relevant financial interests. From the Department of Urology; and Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC Reprint requests: Gopal Badlani, M.D., Department of Urology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157. E-mail: [email protected] Submitted: April 3, 2012, accepted (with revisions): April 6, 2012

Published by Elsevier Inc.

plications resulting from surgical technique vs the mesh. We also analyze American Urological Association (AUA) members’ responses to a questionnaire on their education and use of mesh, as well as correlate lessons from mesh use for abdominopelvic hernia repair.

MATERIAL AND METHODS A PubMed search for RCTs and meta-analyses in English since 2007 was performed. In addition, landmark publications before 2007 are included, as well as a review of epidemiology, the genetic causes of POP, and general surgical hernia repair with mesh. Key words include POP, synthetic mesh, complications, genetics, hernia. Ninety-five articles were considered in the process; on the basis of subject relevance, only 45 are included in the review. We also performed an Internet survey of AUA members regarding their training and use of synthetic mesh.

Epidemiology of POP A recent investigation has demonstrated POP’s association with age. Nygaard et al2 performed a cross-sectional analysis of 1961 women participating in the 2005-2006 National Health and Nutrition Examination Survey (NHANES). Their evaluation revealed an overall prevalence of symptomatic POP, defined as sensation of vaginal bulging, to be 2.9% in women over 20 years old, with a prevalence of 3.8% for ages 40-59, 3% for ages 60-79, and 4.1% for ages ⬎80. Wu et al3 used these numbers and population projections from the 2000-2010 US Census Bureau to estimate that as many as 9.2 million women will have symptomatic POP by 2050. In another populationbased study, the Reproductive Risks for Incontinence Study recruited 2001 women from a Californian health maintenance organization from 1999-2003. In this cohort, Rortveit et al4 report a 5.7% prevalence of symptomatic prolapse, defined as sensation or visualization of vaginal bulge, with 47% of these women experiencing moderate to severe distress. 0090-4295/12/$36.00 http://dx.doi.org/10.1016/j.urology.2012.04.008

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Although disease prevalence is important, perhaps a better marker for severity is the need to undergo surgical treatment for symptom relief. In a landmark study, Olsen et al5 retrospectively evaluated 395 women who had surgery for prolapse or incontinence in 1995 and observed that a woman has an 11.1% lifetime risk of undergoing an operation for these complaints. Furthermore, they noted that 29.2% had previously undergone a traditional repair. Unfortunately, the authors did not perform subgroup analyses; thus the utility of this study is limited when considering prolapse alone. Shah et al6 specifically examined rates of POP surgery in United States women by analyzing ICD-9 codes from the 2003 National Hospital Discharge Survey (NHDS), revealing a surgical rate of 18/10,000 women. Agegroup analysis found rates of 24/10,000 for ages 40-59, 31/ 10,000 for ages 60-79, and 17/10,000 for ages ⬎80. Providing evidence-based counseling to patients requires close monitoring of surgical outcomes. Part of the debate surrounding mesh use has been the lack of consistent or clinically pertinent outcomes measurements. Weber et al7 randomized women with anterior wall prolapse to three different repair techniques. On the basis of the definition from the 2001 National Institutes of Health Workshop on Standardization of Terminology for researchers in Pelvic Floor Disorders (pelvic organ prolapse quantification [POP-Q], points Aa and Ba ⱕ -2 cm with or without symptoms), they found surgical repair failure ranging from 54-70%. Using an updated and “clinically relevant” definition of success, Chmielewski et al8 reanalyzed the data, reporting a recurrence of only 12% in the standard colporrhaphy group. This definition was based on a recommendation by the Pelvic Floor Disorders Network to include symptomatic and anatomic criteria along with absence of reoperation in the outcomes measurements.9 This emanated from the CARE trial by Barber et al,9 in which surgical success of abdominal sacrocolpopexy ranged from 19.2-97.2% depending on the definition. Furthermore, the CARE trial demonstrated that anatomic success alone did not correlate with patient assessment of global improvement, whereas patient-reported lack of symptomatic vaginal bulge was associated with improvement. In the Pelvic Organ Support Study, Swift et al10 evaluated a diverse group of 1004 women presenting for routine gynecologic visits for presence of prolapse, finding that 24% had stage 0 POP-Q, 38% stage I, 35% stage II, and 2% stage III; none had stage IV. Although percentage of symptomatic patients is not reported, they did observe a correlation between increasing degree of prolapse and bother. This study is limited, however, in that it under-reports severe cases, skewing their analysis of symptomatic disease.

Genetic and Biochemical Factors Underlying POP The individualized approach to surgical repair of POP requires careful consideration of all possible contributing factors to the condition, along with ongoing or future insults. A genetic study using the Swedish Twin registry demonstrated that genetic contribution accounted for 43% of the variation for POP.11 Familial studies have also shown that women with a family history of prolapse and hernia were at a higher risk of developing POP.12,13 The familial predisposition may be explained by genetic alterations. POP has also been linked with chromosome 9q21, an area with genes for proteins highly expressed in muscle.14 More recently, six loci on different genes were found to have single nucleotide polymorphisms (SNPs) associated with POP in 115 case group participants.15 Epigenetic regulation of the extracellular matrix (ECM) likely plays a strong role in pelvic floor support.16 The pelvic 238

floor is an anatomic arrangement of smooth and skeletal muscles, ligaments, and fascia. Substances like collagen and elastin provide extraordinary compliance and elasticity in the ECM of fascia and ligaments. Collagen synthesis and breakdown renders the ECM a very dynamic structure through a constant process of remodeling. Candidate gene and case-control studies have located high-frequency SNPs in women with prolapse for genes, such as LAMC117 and MMP-9.18 More than 20 different types of MMPs are largely responsible for collagen breakdown throughout the body. The interstitial and neutrophil collagenases (MMP-1, MMP-8, MMP-13) cleave fibrillar collagen, and the gelatinases (MMP-2 and MMP-9) degrade the denatured peptides. These mutations alter ECM metabolism, increasing predisposition to pelvic floor disorders. A strong genetic predisposition in a woman with an initial or recurrent clinical presentation of POP should be taken into account in the surgical decision making process. These patients may possibly have a weaker pelvic floor with disorganized tissue repair, thereby favoring the use of mesh. This holds true especially for severe anatomic disease because there is significantly higher risk of prolapse recurrence after traditional surgical repair without mesh in women with stages 3-4 prolapse.19 By contrast, their inherent altered ECM metabolism may increase their likelihood of complications like erosion, although the literature does not suggest or disprove this. Several studies suggest a correlation between the development of POP and other acquired diseases involving connective tissue laxity, such as hiatal and inguinal hernias.20,21 The evolution of synthetic mesh use can be observed in abdominopelvic hernia repair where treatment with synthetic biomaterials has become standard practice.22 Treatment efficacy is significantly improved with the incorporation of mesh, and it has been widely accepted despite the uniquely associated complications. Similar to controversies over mesh for POP repair, there are no definitive conclusions regarding which of the many products may be most efficacious and safe.23 Although trials to answer such questions are underway, synthetic mesh will remain one of the primary treatment options for hernias. The use of mesh for these 2 applications diverges, though, in the different tissue milieu of the abdomen and pelvis. Whereas abdominal adhesions are the scourge of the general surgeon, tension-free repair of SUI/POP depends on such tissue responses to anchor the mesh. Furthermore, the abdominal wall is not subjected to the same mechanical stress as is the pelvic floor. This has ramifications in the preclinical biocompatibility testing of synthetic materials because abdominal wall defects in animal models are used to measure tissue responses. Such studies cannot reliably predict how mesh will behave in vivo and thus data extrapolation to humans is limited.24 However, more studies are emerging in which the biomechanical properties of implanted mesh are investigated. Woodruff et al25 performed histopathologic examination of 5 different pubovaginal grafts explanted from human patients, finding variable host remodeling characteristics for each type of graft. Although not clinically correlated, this study epitomizes the importance of investigating etiologies of local complications and functional alternations, which have efficacy and safety implications.

Outcomes from RCTs and Meta-Analyses Between 2007 and 2011, there were 11 published complete RCTs (Table 1) and 2 meta-analyses comparing traditional repair to synthetic mesh augmentation; outcome reporting varies significantly. In 2007, Hiltunen et al26 randomized 201 UROLOGY 80 (2), 2012

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Table 1. Reported outcomes and complications of RCTs

n

Primary Outcome Results (P value)

Rates of Symptomatic Recurrence

Mesh-specific Complications and Treatment

Re-operation for POP Recurrence

104 97

38.5% 6.7% (P ⬍.001)

14 patients 4 patients (P ⫽ .005)

1 patient in the AC group

AC STM AC Perigee

42 43 37 37

72% 91% (P ⬍.05) 55% 87% (P⫽ .005)

NR NR 1 patient 0 patients

Surgical success: ⱕstage I POP-Q at any site (anterior/ posterior prolapse) POP recurrence: Ba ⬎0 POP-Q (uterine prolapse)

A&P STM

61 63

65.5% 81% (P ⫽ .07)

NR NR

SSLF Nazca

15 14

44% 57% (P ⫽ .8)

NR NR

POP recurrence: ⱖstage II POP-Q (apical /anterior prolapse) POP recurrence: ⱖstage II POP-Q (anterior prolapse)

VC Prolift

33 32

70.4% 59.5% (P ⫽ .28)

NR NR

AC STM

97 105

1y

POP recurrence: ⱖstage II POP-Q (recurrent prolapse at any site)

CR Prolift

Maher et al, 201136

2y

Altman et al, 201131

1y

Vollebregt et al, 201132

1y

Surgical success: ⱕstage 1 POP-Q at any site (vault prolapse) Surgical success: 1. ⱕstage 1 POP-Q 2. No vaginal bulge sensation (anterior prolapse) Surgical success: ⬍stage II POP-Q (cystocele)

Primary Outcome: Criteria (defect treated)

Compared Procedures

Author, year Published

F/U

Hiltunen et al, 200726

1y

POP recurrence: ⱖstage II POP-Q (anterior prolapse)

AC STM

Sivaslioglu et al, 200827 Nguyen and Burchette, 200828

1y

Surgical success: ⱕstage I POP-Q (cystocele) Surgical success: ⱕstage I POP-Q (anterior prolapse)

Carey et al, 200933

1y

Lopes et al, 201034

1y

Iglesia et al, 201035

3 mo.

Nieminen et al, 201029

3y

Withagen et al, 201130

1y

41% 13% (P ⬍.0001)

26 patients 9 patients

97 93

45.2% 9.6% (P ⬍.001)

4 patients 0 patients

LSC Prolift

53 55

77% 43% (P ⬍.001)

1 patient 4 patients

17.3% anterior wall exposure 78% local excision of mesh 22% topical estrogen 6.9% vaginal erosion 100% local excision of mesh 5% incisional extrusion 0% symptomatic 100% local excision of mesh 5.6% exposure 75% local excision of mesh 25% topical estrogen 35.7% erosion 20%/20% local/full excision 60% topical estrogen 15.6% erosions 60% local excision of mesh 40% topical estrogen 19% exposure 70% local excision of mesh 30% topical estrogen 16.9% exposure 65% asymptomatic 35% local excision of mesh 65% topical estrogen 2% 9%

AC Prolift

182 186

34.5% 60.8% (P ⬍.001)

38% 25% (P ⫽ .008)

Total exposure rate NR 3% had revision of mesh

1 patient in AC group

56 58

41% 91% (P ⬍.001)

NR NR

4% exposure 100% local excision of mesh

3 patients in AC group

AC Avaulta

NR 1 patient in the AC group

2 patients in the AC group 1 patient in mesh group for vault prolapse NR

8 patients in AC group

4 patient in CR group

3 patients in mesh group

AC ⫽ anterior colporrhaphy; A&P ⫽ anterior and posterior colporrhaphy; CR ⫽ conventional repair; F/U ⫽ mean length of follow-up; NR ⫽ not reported; STM ⫽ surgeon-tailored mesh; VC ⫽ vaginal colpopexy.

239

postmenopausal women with anterior prolapse alone to anterior colporrhaphy with (n ⫽ 104) or without (n ⫽ 97) surgeontailored, low-weight polypropylene mesh (Parietex, Sofradim); there were no concomitant procedures for SUI. Recurrence of disease, defined as prolapse ⱖstage II POP-Q, occurred in 38.5% of the nonmesh group and 6.7% of the mesh group (P ⬍.001) at 1-year follow-up. There were no significant differences between mesh and nonmesh groups in regards to subjective outcomes, such as pelvic pressure or vaginal bulge. In another study, Sivaslioglu et al27 randomized women with cystoceles to either transvaginal mesh repair (n ⫽ 43; Parietex, Sofradim) or colporrhaphy (n ⫽ 42), and determined the cure rates as defined as prolapse ⱕstage I POP-Q. Patients with concomitant SUI were excluded. At 1-year follow-up, anatomic cure was achieved in 91% of the mesh group vs 72% of the nonmesh group (P ⬍.05). There was no significant difference between groups overall in a postoperative quality-of-life questionnaire (P-QoL). However, when the questionnaire was broken down into individual symptom complexes, the mesh group had significantly less abnormal emptying, frequency, urgency, and pelvic pain, and the nonmesh group reported improved symptoms in abnormal emptying and urgency parameters only. Nguyen et al28 randomized 74 women with anterior prolapse to either colporrhaphy (n ⫽ 37) or transvaginal polypropylene mesh repair (n ⫽ 37; Perigee, AMS). A majority of patients in each group also had a midurethral sling placed for SUI. The mesh group had a significantly higher optimal or satisfactory pelvic support at 1 year, defined as prolapse ⱕstage I POP-Q compared with the traditional repair group (87% vs 55%, P ⫽ .005). Overall, most patients with anatomic recurrence were asymptomatic, with only 1 patient in the nonmesh group requiring a secondary procedure. Both groups had significant postoperative improvement in scores on 2 validated questionnaires—PFDI-20 and PFIQ-7— but there was no significant difference between groups overall. Interestingly, the mesh group did have significantly better scores in the prolapse and urinary subscales of the PFDI-20. In a multicenter RCT with the longest follow-up period published to date, Nieminen et al29 randomized 105 women to surgeon-tailored transvaginal mesh (Parietex, Sofradim) and 97 women to traditional colporrhaphy for anterior wall prolapse. Patients with concomitant SUI were excluded. At 3 years follow up, the authors reported recurrence of prolapse ⱖstage II POP-Q to be 13% in the mesh group vs 41% in the traditional repair group (P ⬍.0001). Although the proportion of postoperative recurrence of symptomatic bulging sensation was similar in each group (65% for nonmesh group vs 69% in mesh group), there was a significant difference favoring the mesh group if optimal outcome was defined as absence of anatomic recurrence and lack of vaginal bulge sensation (82% vs 55%, P ⬍.0001). Although no validated questionnaires were used, there was no difference between groups in other secondary measures of global improvement. In a comprehensive RCT, including patients with recurrent prolapse in anterior, posterior, or apical vaginal compartments, Withagen et al30 observed that overall 9.6% of women who underwent trocar-guided, tension-free vaginal mesh (n ⫽ 93; Gynecare Prolift, Ethicon) had anatomic failure in the treated compartment compared with 45.2% of women who had a traditional procedure (n ⫽ 97) at 1 year follow-up (P ⬍.001). There was no difference between groups when considering apical failure, but the mesh group performed significantly better in both anterior and posterior compartments. Interestingly, if the definition of failure was changed to prolapse 240

ⱖstage II POP-Q in any compartment, failure rates increased to 49% in the mesh group and 66% in the traditional repair group, but still significantly favored mesh repair (P ⬍.05). Despite having better anatomic outcomes, however, there were no significant differences in secondary outcome questionnaires (UDI, DDI, IIQ, PGI-I). In the largest multicenter RCT comparing traditional repair with a commercialized mesh kit (Gynecare Prolift, Ethicon), Altman et al31 randomized women with cystoceles to either anterior colporrhaphy (n ⫽ 182) or trocarguided, transvaginal polypropylene mesh repair (n ⫽ 186). The primary outcome at 1-year follow-up was defined in terms of anatomic success (POP-Q ⱕstage I) plus subjective success (absence of a vaginal bulging sensation) and was found in 60.8% of the mesh group but in only 34.5% of the nonmesh group (P ⬍.001). Furthermore, the mesh group had significantly less vaginal bulge symptoms at 1 year compared with the colporrhaphy group (75.4% vs 62.1%, P ⫽ .008). When comparing secondary outcomes between groups, however, there was no significant difference in overall postoperative UDI or PISQ-12 scores. In another study, Vollegregt et al32 found a 91% anatomic cure rate at 1-year follow-up in 58 women undergoing trocar-guided transvaginal mesh repair (Avaulta, Bard) compared with 41% cure rate in 56 women who had a traditional procedure for cystocele repair (P ⬍.001). Both UDI and IIQ questionnaire scores were assessed as secondary outcomes, but there was no significant difference in overall scores between groups. Overall, most trials report better anatomic success rates in the mesh-based procedures but do not demonstrate any significant differences in functional or quality-of-life outcomes. Several other trials have not found synthetic mesh to be superior to traditional repair. Carey et al33 reported on their 1-year follow-up comparing 63 women undergoing transvaginal surgeon-tailored mesh repair (Gynemesh PS, Ethicon) for anterior or posterior wall prolapse to 61 women who had traditional colporrhaphy. Midurethral slings for SUI were concomitantly placed in both groups. Although anatomic success, defined as prolapse ⬍stage II POP-Q, was higher in the mesh group (81% vs 65.6%), it did not reach statistical significance (P ⫽ .07). For secondary outcomes, scores from several questionnaires measuring quality of life (PSI-QOL, SUDI, SIIQ, CCCS) were not different between groups. In a small RCT, Lopes et al34 randomized 30 women with apical prolapse to either sacrospinous ligament fixation (n ⫽ 16) or transvaginally placed polypropylene mesh kit (n ⫽ 14; Nazca, Promedon). The recurrence rates at the anterior wall (57% for the mesh group and 44% for the sacrospinous ligament fixation [SSLF] group) and the measures of quality of life were not significantly different at 1-year follow-up between groups. In an RCT that was prematurely halted because of complications in the mesh group, Iglesia et al35 randomized women with apical or anterior prolapse to either Gynecare Prolift transvaginal mesh repair (n ⫽ 32; Gynecare Prolift, Ethicon) or vaginal colpopexy (n ⫽ 33). Overall, recurrence of prolapse at 3 months was similar between groups, as were subjective measures of vaginal bulge. Finally, Maher et al36 randomized women with vaginal vault prolapse to laparoscopic sacral colpopexy (LSC, n ⫽ 53) vs total vaginal mesh (n ⫽ 55; Gynecare Prolift, Ethicon) and evaluated outcomes 2 years postoperatively. The LSC group had better objective cure of prolapse, with 77% success rate vs 43% in the mesh group (P ⬍.001). There were no differences between groups in the improvement of functional or quality-oflife questionnaire scores. UROLOGY 80 (2), 2012

Meta-analyses can effectively analyze data from multiple reports to generate higher-powered results, but their application extends only as far as the quality of the studies they review. Because trials evaluating efficacies of nonabsorbable synthetic mesh exhibit a high degree of variability, accurate meta-analysis is difficult. Jia et al37 carried out an international review on anterior or posterior wall prolapse, analyzing studies from 19802007, only revealing enough high-quality data to report results in anterior repair. Using a Bayesian meta-analysis model, any type of adjuvant mesh resulted in lower objective failure rates compared with standard techniques, with nonabsorbable synthetic mesh conferring a significantly lower objective failure rate when compared with absorbable synthetic mesh (OR 0.23, CI 0.12-0.44) or absorbable biological mesh (OR 0.37, CI 0.23-0.59). Summarizing the 2011 Cochrane review, Maher et al38 also report that no definitive conclusions can be drawn about mesh use for posterior or apical vaginal repair. Regarding anterior wall prolapse, however, anterior colporrhaphy had higher rates of objective failure in the same compartment compared with polypropylene mesh onlay (RR 2.14, CI 1.233.74) and surgeon-tailored or commercial transobturator mesh kits (RR 3.55, CI 2.29-5.52). Although both meta-analyses demonstrate higher objective/anatomic success of synthetic mesh use, neither can conclude that there are increased subjective success rates or improved quality of life parameters compared with traditional repair techniques.

Evaluating the RCTs and Meta-Analyses The initial lack of high-quality data could not guide physicians in the appropriate use of synthetic mesh-based procedures because there was scant Level 1 evidence published in the years after the FDA’s approval. Over the past few years, however, multiple RCTs and meta-analyses have helped provide higherquality outcomes data regarding the use of synthetic mesh. The RCTs reviewed are very well-designed, and all but one met statistical power requirements. However, individual results must be interpreted with caution because most conclusions are weakened by their nonblinded outcomes assessment. Generalization of these results is also significantly limited because surgical methodologies between trials are known to vary. Specifically regarding efficacy, though, mesh-based procedures provide equal or greater short-term anatomic cure rates compared with traditional repair, particularly for anterior vaginal wall prolapse. Most RCTs only report short-term outcomes, however, and thus cannot be extrapolated to long-term results. Also, there is no consensus data to suggest mesh use for apical or posterior compartment prolapse repair at this time. No investigation has documented significantly improved patient reported outcomes when comparing the different repair methods. For these reasons, widespread use of mesh for POP cannot be recommended over traditional repair without a caution. Perhaps more important are the potential complications and safety implications associated with mesh-based repair, which should be discussed with the patient when considering its use.

Complications of Mesh-Based Repair Erosion through tissue planes is the principal obstacle in meshbased repair. In these RCTs, rates of documented erosion range from 4-35.7% (Table 1).26-36 Reporting of exact erosion location (incision site vs vaginal wall) and symptomatic occurrences is low. Most erosions were treated under local anesthesia by partial excision of the eroded mesh, and the rest needed only UROLOGY 80 (2), 2012

Table 2. AUA member survey results* Current Use of mesh-based Procedures by Practicing Urologists† Urologists who use mesh 86.8% Average mesh cases per month 5 (range 0–100) For SUI 4.27 (range 0–100) For POP 1.34 (range 0–35) Sources of mesh-based procedure training‡ Self-instructed 31.9% Company course 25.9% Company hands-on course 48.8% Specialty Society hands-on course 5.7% Fellowship 9.7% Residency 22.3% * A SurveyMonkey web-based survey was e-mailed to 8008 registered AUA members who had validated e-mail addresses and practice in the United States in September 2011. † Total response rate of 16.6% (1329 responses). ‡ More than one answer could be selected.

topical estrogen. Few cases required full removal. After coalescing data from multiple studies, Maher et al38 calculated an overall erosion rate of 10%, similar to the 10.2% rate reported by Jia et al,37 who also found that only 6.6% of all cases required surgical excision. In a recent systematic review, Abed et al39 report an erosion rate of 10.3% for all synthetic mesh procedures. In a review analyzing apical prolapse repair using vaginal mesh kits, Diwadkar et al40 report an overall erosion rate of 5.8%. Although this study determined that the total complication rate was higher for sacral colpopexy (17.1% vs 14.5% for mesh kits), vaginal mesh kits induced more severe complications requiring surgical correction. Such reports, along with the increasing rate of complications reported to the FDA’s MAUDE database, prompted the FDA to release its warning regarding mesh for POP repair. Unfortunately, there are several important issues that are often not included in these discussions. First is the lack of distinction between complications caused by surgical technique as opposed to the mesh itself. Many technique-related factors increase the risk for mesh erosion, such as concurrent hysterectomy, incision type, and depth of tissue dissection. In fact, the high erosion rate reported in one of the RCTs (35.7%) was attributed to the mesh placement in relation to the rectovaginal fascia.34 Moreover, Maher et al38 determined that there are no significant differences in the incidence of other postoperative complications, such as de novo SUI or dyspareunia, compared with traditional repair. Other complications, such as intraoperative injuries, bleeding, and hematomas are caused primarily by mesh insertion techniques, not by the presence of mesh. This leads to other critical issues that are often neglected, namely the role of surgeon education, as well as how market forces affect practice standards. Increasing surgical experience leads to improved outcomes in any field, and this has been observed in the arena of mesh-based repairs.41 The rapidly increasing availability of new devices may not only prevent appropriate training, but also discourages the completion of RCTs as new products are marketed before a trial can be completed.42,43 We performed a survey of all currently practicing AUA members who were e-mailed a 7-question survey regarding their training and current use of synthetic mesh in daily practice (Table 2). On the basis of the responses, 75% of urologists received training for mesh-based repair techniques at an industry-sponsored course, with only 49% receiving 241

Table 3. IUGA/ICS terminology classifications* Terms Prosthesis

Mesh Implant Tape (sling) Graft

Complication-specific terminology† Erosion

Exposure

Extrusion Perforation

Definition A fabricated substitute to assist a damaged body part or to augment or stabilize a hypoplastic structure A (prosthetic) network fabric/ structure A surgically inserted/embedded prosthesis A flat strip of synthetic material Any tissue or organ for transplantation; this term will refer to biological materials inserted “does not necessarily suit the clinical scenarios. . . and its use is best avoided, to be replaced by terms with greater physical specificity and clarity.”44 A condition of displaying, revealing, exhibiting, or making accessible, eg, vaginal mesh visualized through separated vaginal epithelium. Passage gradually out of the body structure or tissue Abnormal opening into a hollow organ or viscus

* Adopted from Haylen et al. An International Urogynecological Association (IUGA)/International Continence Society (ICS) joint terminology and classification of the complications related directly to the insertion of prostheses (meshes, implants, tapes) & grafts in female pelvic floor surgery. Int Urogynecol J. 2011;22: 3-15.45 † The reviewed studies may not have followed these definitions when reporting complications, and thus the original language in the articles are used for this review.

hands-on guidance. Although we are unsure of how many of these urologists initially had specialty training, one third of all responders indicated they were self-instructed, whereas only 10% reported training for mesh implantation techniques during fellowship.

CONCLUSIONS The ideal synthetic mesh likely has not yet been developed.42 As current research endeavors provide a greater understanding into the risk factors and etiologies of POP, the development of treatment modalities with greater efficacies and lesser complications can be achieved. However, it must be ensured that new technologies be adequately evaluated and tested and that surgeons undergo appropriate training before large-scale market competition forces its disseminated use. Although intended primarily to warn patients of potential complications associated with mesh-based repair, the FDA’s Safety Communication in July of 2011 has also served as a wake-up call for physicians and has encouraged medical 242

organizations to take a bigger role in developing practice policies. The AUA, the American College of Obstetricians and Gynecologists, as well as the American Urogynecologic Society have made specific recommendations that emphasize appropriate surgical education and call for high-quality comparative trials in POP while supporting the mesh’s use as a midurethral sling for SUI.44 Development of use and outcome registries will provide a better evaluation of rates of mesh-related complications. Standardization of complication reporting has been initiated by the International Urogynecological Association and International Continence Society (Table 3),45 and this will we hope assist in delineating various etiologies of complications. It is imperative that such standardization also be applied to better define the disease state, as well as surgical outcome measures. Such policies will assist in proper patient phenotyping and clinical decision making. Incorporating both objective and patient-reported subjective outcomes in defining disease states, surgical success, or disease recurrence is absolutely essential. For situations in which controversy abounds, there is an immense opportunity to advance knowledge and understanding of the issue in dispute. Such is the case with using synthetic mesh for the treatment of POP. The application of mesh should not be ubiquitous to all patients, nor should its availability be stricken from the surgeon’s armamentarium. Further research into disease etiology along with improved physician training in surgical skill and patient assessment will help identify women who would or would not benefit from a meshbased repair. Currently, however, it is the surgeon’s duty to fully inform the patient and discuss the risks vs benefits of such procedures. Just as important, the surgeon must also reflect on and judge their surgical competency, being allowed to decide what is best for individual patients.46,47

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