The 4 groups are based on the amount of mesh exposure as follows: transvaginal pelvic organ prolapse (POP) repair surgery with mesh and concurrent sling use (vaginal mesh plus sling group), transvaginal POP repair with mesh and no concurrent sling use (vaginal mesh group), transvaginal POP repair without mesh but concurrent sling use for stress urinary incontinence (SUI) (POP sling group), and sling for SUI alone (SUI sling group).
The 4 groups are defined in the Figure 1 caption. POP indicates pelvic organ prolapse; SUI, stress urinary incontinence.
eTable 1. Definition of Procedures
eTable 2. Estimated Risks of Events and 95% Confidence Intervals at 1 Year Follow-up With Time to Event Analysis Among New York State Residents
eTable 3. National Estimates of Total Women Affected (Mean Follow-up 3.4 Years) in a 5-Year Cohort
eFigure 1. Patient Selection Process
eFigure 2. Time to Repeated Surgery Related to Erosion Following Index Procedures: (A) Standard Kaplan-Meier Analysis and (B) With Competing Risk Analysis
eFigure 3. Age Stratified Analysis of Estimated 1-Year Outcome Risks Following Index Procedures
Chughtai B, Barber MD, Mao J, Forde JC, Normand ST, Sedrakyan A. Association Between the Amount of Vaginal Mesh Used With Mesh Erosions and Repeated Surgery After Repairing Pelvic Organ Prolapse and Stress Urinary Incontinence. JAMA Surg. Published online November 30, 2016. doi:10.1001/jamasurg.2016.4200
What is the association between the amount of vaginal mesh used with mesh erosions and repeated surgery after pelvic organ prolapse repair and urinary incontinence surgery?
In this observational cohort study, the highest mesh erosion risk was found in women receiving transvaginal pelvic organ prolapse repair surgery with mesh and concurrent sling use (vaginal mesh plus sling group). The risks of repeated surgery overall and repeated surgery with concomitant erosion diagnosis were also the highest in the vaginal mesh plus sling group and were the lowest in women receiving a sling for stress urinary incontinence alone.
There is a dose-response relationship between the amount of mesh used and subsequent erosions and other complications, leading to repeated surgery.
Mesh, a synthetic graft, has been used in pelvic organ prolapse (POP) repair and stress urinary incontinence (SUI) to augment and strengthen weakened tissue. Polypropylene mesh has come under scrutiny by the US Food and Drug Administration.
To examine the rates of mesh complications and invasive reintervention after the placement of vaginal mesh for POP repair or SUI surgery.
Design, Setting, and Participants
This investigation was an observational cohort study at inpatient and ambulatory surgery settings in New York State. Participants were women who underwent transvaginal repair for POP or SUI with mesh between January 1, 2008, and December 31, 2012, and were followed up through December 31, 2013. They were divided into the following 4 groups based on the amount of mesh exposure: transvaginal POP repair surgery with mesh and concurrent sling use (vaginal mesh plus sling group), transvaginal POP repair with mesh and no concurrent sling use (vaginal mesh group), transvaginal POP repair without mesh but concurrent sling use for SUI (POP sling group), and sling for SUI alone (SUI sling group).
Main Outcomes and Measures
The primary outcome was the occurrence of mesh complications and repeated invasive intervention within 1 year after the initial mesh implantation. A time-to-event analysis was performed to examine the occurrence of mesh erosions and subsequent reintervention. Secondary analyses of an age association (<65 vs ≥65 years) were conducted.
The study identified 41 604 women who underwent 1 of the 4 procedures. The mean (SD) age of women at their initial mesh implantation was 56.2 (13.0) years. The highest risk of erosions was found in the vaginal mesh plus sling group (2.72%; 95% CI, 2.31%-3.21%) and the lowest in the SUI sling group (1.57%; 95% CI, 1.41%-1.74%). The risk of repeated surgery with concomitant erosion diagnosis was also the highest in the vaginal mesh plus sling group (2.13%; 95% CI, 1.76%-2.56%) and the lowest in the SUI sling group (1.16%; 95% CI, 1.03%-1.31%).
Conclusions and Relevance
The combined use of POP mesh and SUI mesh sling was associated with the highest erosion and repeated intervention risk, while mesh sling alone had the lowest erosion and repeated intervention risk. There is evidence for a dose-response relationship between the amount of mesh used and subsequent mesh erosions, complications, and invasive repeated intervention.
Stress urinary incontinence (SUI) and pelvic organ prolapse (POP) are common conditions affecting women, and they often coexist.1,2 An estimated 1 in 5 women will undergo surgery for POP or SUI by age 80 years in the United States.1 Since the 1970s, several graft materials have been used to augment POP repair and incontinence surgery in women.3 In 1996, the first mesh (a synthetic graft) was approved for the surgical treatment of incontinence to reinforce weakened tissue.3
Augmenting POP repairs with large amounts of mesh and the use of smaller amounts of mesh (sling) for SUI repairs is thought to increase success rates of both operations but has been shown to be associated with chronic pain,4 urethral fistula,5 significant voiding dysfunction,6 and mesh erosions and migrations into surrounding organs.7 These major complications of mesh use with POP and SUI may require one to several surgical interventions to revise or remove the mesh8,9 and can leave patients with permanent residual symptoms and emotional distress.10
The US Food and Drug Administration (FDA) released a public health notification11 in 2008 and an updated notification12 in 2011 that placed the use of mesh for POP under national scrutiny. In contrast, the FDA noted that the safety and efficacy of smaller amounts of mesh used in midurethral slings are well established in clinical trials within 1-year follow-up.13 However, longer-term studies are lacking. The FDA alerted that the use of mesh-based slings may potentially lead to some complications, notably mesh erosions, that are not present with nonmesh procedures.12 The American Urological Association10 guidelines for the surgical management of SUI stated that a sling is an appropriate treatment for women with stress incontinence, with similar efficacy but less morbidity than conventional nonmesh sling techniques. Furthermore, in a position statement,14 the American Urogynecologic Society and the Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction supported the use of midurethral slings in the surgical management of SUI.
Mesh used for POP is now a class 3 (highest risk) device, upgraded from a class 2 device, while mesh slings remain class 2. The FDA warnings about the use of mesh for vaginal repair of POP, the risk of mesh erosions with slings for SUI, and the proliferation of these procedures highlight the public health need to provide evidence on mesh erosion and repeated surgery occurrence for these therapies. We sought to examine the risk of mesh erosions that require management, the incidence of repeated surgery with concomitant erosion diagnosis, and the overall prevalence of repeated surgery after transvaginal repair for POP and SUI. We conducted a population-based observational cohort study to identify the occurrence of these events among patients exposed to various amounts of mesh.
We used data from the New York State Department of Health Statewide Planning and Research Cooperative System (SPARCS). Established in 1979, SPARCS is a longitudinal database comprising all age groups and all payers that collects patient and treatment information for every hospital discharge, ambulatory surgery, and emergency department admission in New York State.15 The study was approved by the Weill Cornell Medical College Institutional Review Board. Because the study used an administrative database maintained by New York State, no informed consent was needed for study participants.
Women undergoing surgical procedures for POP or SUI with mesh in inpatient and ambulatory surgery settings in New York State between January 1, 2008, and December 31, 2012, were identified using International Classification of Diseases, Ninth Revision, Clinical Modification procedure codes and Current Procedural Terminology, Fourth Edition codes (eTable 1 in the Supplement). The last day of the study period was December 31, 2013, to allow 1-year follow-up for every patient. We further divided our study population into the following 4 groups of patients based on the extent of mesh use for their first POP repair or SUI surgery (index procedure): (1) transvaginal POP repair surgery with mesh and concurrent sling use (hereafter vaginal mesh plus sling group), (2) transvaginal POP repair with mesh and no concurrent sling use (hereafter vaginal mesh group), (3) transvaginal POP repair without mesh but concurrent sling use for SUI (hereafter POP sling group), and (4) sling for SUI alone (hereafter SUI sling group). Patients who had previous POP repair or sling surgical procedures before the index procedure were excluded to avoid the inclusion of patients who received mesh-related procedures before the beginning of the present study. Abdominal or laparoscopic POP repairs and sling surgical procedures were excluded to focus on transvaginal surgery with mesh. The patient selection process is shown in eFigure 1 in the Supplement.
Patient demographics included age, race/ethnicity, and insurance payer. Relevant comorbidities were identified using algorithms validated by Elixhauser et al.16 Settings where the index procedure was performed were defined as inpatient and outpatient (ambulatory surgery) based on state-provided categorization.
Patients were followed up for 1 year after the index procedure to examine the following outcome events: (1) repeated surgery; (2) erosions requiring inpatient, emergency department, or ambulatory surgery management; and (3) repeated surgery with concomitant erosion diagnosis. Repeated surgery was defined as having another POP or SUI surgery or revision or removal of mesh. Patients who did not undergo repeated surgery were censored at the end of follow-up. Erosions were identified using recently designated and validated codes.17 Patients were censored at the time of repeated surgery if that procedure occurred before an erosion diagnosis or at the end of follow-up when no erosions occurred. Repeated surgery with concomitant erosion diagnosis was defined as diagnoses before or at the time of a second procedure. Patients were censored at the time when a competing event occurred (repeated surgery owing to other causes) or at the end of follow-up when they did not undergo repeated surgery.
Patient demographics and procedure settings were assessed. Events and percentages were calculated for categorical variables, and means (SDs) were calculated for age. We evaluated 1-year risk of repeated surgery, erosions that required management, and repeated surgery with concomitant erosion diagnosis in the 4 groups. We examined the median (interquartile range [IQR]) time to repeated surgery, to erosions, and to repeated surgery with concomitant erosion diagnosis.
Kaplan-Meier analysis was performed to obtain estimated risks of repeated surgery, erosions, and repeated surgery with concomitant erosion diagnosis at 1-year follow-up. Competing risk analysis was used to estimate the risk of repeated surgery with concomitant erosion diagnosis. Estimated risk of repeated surgery with concomitant erosion diagnosis at 1 year was obtained with cumulative incidence function.18 Five-year national estimates of affected women were then calculated based on New York State and US female populations using the US 2010 Census.19 We repeated these analyses with stratification by patient age (<65 vs ≥65 years). Sensitivity analysis was conducted among New York State residents. All analyses were performed using statistical software (SAS, version 9.3; SAS Institute Inc).
The study identified 41 604 women who underwent 1 of the 4 procedures. The mean (SD) age of women at their initial mesh implantation was 56.2 (13.0) years.
Between 2008 and 2012, a total of 5070 patients comprised the vaginal mesh plus sling group. Another 3798 patients were in the vaginal mesh group, and 10 484 patients were in the POP sling group. There were 22 252 patients in the SUI sling group.
There were some differences in patient characteristics across the 4 study groups (Table 1). The mean (SD) age of the patients in the vaginal mesh plus sling group was 62.4 (12.1) years old vs 52.6 (12.2) years for patients in the SUI sling group. Most POP repairs occurred in the inpatient setting, while most sling insertions were completed in outpatient settings.
During 1-year follow-up, 2.7% (138 of 5070) of the patients in the vaginal mesh plus sling group, 1.9% (74 of 3798) of the patients in the vaginal mesh group, 1.9% (199 of 10 484) of the patients in the POP sling group, and 1.6% (349 of 22 252) of the patients in the SUI sling group experienced erosions that required management. The median (IQR) days to erosions were 118 (IQR, 49-205), 135 (IQR, 80-207), 126 (IQR, 40-230), and 115 (IQR, 41-207), respectively, in the 4 groups (Table 2). In Kaplan-Meier time-to-event analysis (Figure 1 and Table 3), patients in the vaginal mesh plus sling group had the highest estimated risk of erosions (2.72%; 95% CI, 2.31%-3.21%) at 1 year, while the lowest 1-year erosion risk was observed in the SUI sling group (1.57%; 95% CI, 1.41%-1.74%). The vaginal mesh group (1.95%; 95% CI, 1.56%-2.44%) and the POP sling group (1.90%; 95% CI, 1.65%-2.18%) had similar mesh erosion risk.
The risk of repeated surgery at 1 year was also highest in the vaginal mesh plus sling group (5.64%; 95% CI, 5.04%-6.31%), with a median of 144 (IQR, 55-245) days to repeated surgery (Tables 2 and 3 and Figure 2). The SUI sling group had the lowest repeated surgery risk at 2.53% (95% CI, 2.33%-2.74%), with a median of 123 (IQR, 40-218) days to repeated surgery. The risk of repeated surgery with concomitant erosion diagnosis at 1-year follow-up was again highest in the vaginal mesh plus sling group (2.13%; 95% CI, 1.76%-2.56%) and lowest in the SUI sling group (1.16%; 95% CI, 1.03%-1.31%) (Table 3 and eFigure 2 in the Supplement).
In subgroup analyses by age, the vaginal mesh plus sling group had the highest risks of repeated surgery, erosions, and repeated surgery with concomitant erosion diagnosis in both age groups. The highest risks were observed in the patients younger than 65 years who received mesh for POP and concurrent slings (eFigure 3 in the Supplement). Sensitivity analysis among New York State residents showed consistent association between mesh use with repeated surgery and repeated surgery with concomitant erosion diagnosis (eTable 2 in the Supplement).
At 1-year follow-up, erosions were most common after procedures in which a larger amount of mesh was used, occurring in 2.7% of the patients in the vaginal mesh plus sling group compared with 1.6% in the SUI sling group. Similarly, repeated surgery was highest in the vaginal mesh plus sling group (5.6%) and lowest in the SUI sling group (2.5%). A similar pattern was observed for the end point of repeated surgery with concomitant erosion diagnosis. These data are supportive of a dose-response relationship, providing evidence for an association between the amount of mesh used and erosions. If we translate the risk and extrapolate to the US general population, more than 20 000 erosions and approximately 14 000 repeat surgical procedures with concomitant erosion diagnosis occurred among women in the United States during the 5-year period of our study, with a median of 3.4 years of follow-up (eTable 3 in the Supplement).
To our knowledge, no previous studies have assessed erosion occurrence in groups with differential exposure to mesh. A systematic review by Abed et al20 analyzed all graft materials used for POP and included an analysis of 91 studies enrolling more than 10 000 patients involving mesh. The erosion rate for mesh in patients with POP was reported as 10.3%, with the diagnosis and time to mesh erosions ranging from 6 weeks to 12 months. However, Nguyen et al21 reported a lower 3.4% reoperation risk for vaginal mesh erosions after POP procedures performed during a 21-month period. Their mean time to reoperation for mesh-related complications was 267 days. Our study focuses on mesh erosions that required management. Accordingly, the risks of erosions herein are considerably lower than those reported by Abed et al20 and closer to those reported by Nguyen et al.21
The lower risk of erosions in our study after insertion of a sling for SUI compared with a larger amount of mesh used for POP and SUI is supported by prior studies. Jonsson Funk et al17 analyzed follow-up data of 188 454 women who underwent a sling insertion for SUI. At 1 year, the risk of revision or removal was 2.2%. The risk increased to 3.2% at 4 years, with a 9-year cumulative risk of 3.7%. Welk et al8 recently published an article on the incidence of mesh removal or revision after SUI procedures in the province of Ontario, Canada. During a 10-year period, they identified almost 60 000 women who underwent a mesh-based procedure for SUI and reported that 2.2% of the patients underwent mesh removal or revision after receiving their initial mesh implantation for SUI.
Our group has previously reported that repeated surgery was much higher after mesh-based repair of POP compared with POP repair without mesh.9 In the present study, we extended these results by reporting repeated surgery after 4 different procedures using various amounts of mesh and provide new information on the time to repeated surgery. The shortest time to repeated surgery was found in the SUI sling group. Despite having the lowest risk of repeated surgery, patients in this group had the shortest time to repeated surgery after a median of 123 days. This duration was shorter than that in the study by Welk et al,8 who reported a median time of 343 days (0.94 years) to mesh removal or revision after mesh implantation for SUI. The time to repeated surgery for patients is often dictated by when they experience symptoms suggestive of erosions. Other events that might necessitate repeated surgery include urinary retention in the immediate postoperative period, pain, voiding dysfunction, or dyspareunia, which commonly occurs at a later date.22 The earlier presentation of the patients with mesh for SUI compared with those undergoing POP repair with mesh also may be attributable to the younger age of patients with SUI undergoing sling insertion. Mesh exposure due to tissue friction is more likely to occur in younger patients because they tend to be more sexually active.23
Although New York State SPARCS data include all age groups and all payers, there are some limitations with using this database. Information regarding the severity of POP or SUI cannot be captured through administrative data. In addition, too few abdominal or laparoscopic mesh procedures (ie, sacrocolpopexies) were available in the data set to provide meaningful data for this analysis and were excluded. Follow-up of the patients might be incomplete because some may have relocated to other states. To avoid loss to follow-up, we limited our study to a 1-year outcome evaluation. Erosions diagnosed in a clinic or physician’s office were not captured. We focused primarily on erosions that required management.
The inclusion of the entire state’s data, with recent years and all age groups, makes this study uniquely powerful, novel, and important in understanding a dose-response relationship between the amount of mesh used and subsequent mesh erosions and other complications. This study addresses 2 additional important gaps in the literature. First, POP repairs with mesh and concurrent SUI sling procedures that also use mesh have the highest erosion rates. Second, mesh slings alone for incontinence eroded the fastest, although at a lower frequency than transvaginal POP procedures. Although the FDA initiated 522 studies and creation of a mesh registry for postmarket analysis of mesh outcomes in POP,24 there is no such recommendation for slings. The inclusion of mesh-based slings for postmarket surveillance might need to be considered, despite a lower occurrence of erosions and revision surgery, to ensure safe use of these technologies. Using real-world data, our study helps inform regulators, clinicians, and patients on the safety of mesh, sequelae of erosions, and repeated surgery.
The combined treatment of transvaginal POP repair and SUI using mesh and sling was associated with the highest erosion and repeated surgery risks, and SUI repair with sling alone was associated with the lowest risks. There is evidence for a dose-response relationship between the amount of vaginal mesh used and subsequent mesh erosions and other complications, leading to repeated surgery.
Corresponding Author: Art Sedrakyan, MD, PhD, Department of Healthcare Policy and Research, Weill Cornell Medical College, Ste LA223, 402 E 67th St, New York, NY 10065 (firstname.lastname@example.org).
Accepted for Publication: July 31, 2016.
Published Online: November 30, 2016. doi:10.1001/jamasurg.2016.4200
Author Contribution: Dr Sedrakyan had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Chughtai, Barber, Sedrakyan.
Acquisition, analysis, or interpretation of data: Barber, Mao, Forde, Normand, Sedrakyan.
Drafting of the manuscript: Chughtai, Barber, Mao, Forde, Sedrakyan.
Critical revision of the manuscript for important intellectual content: Chughtai, Barber, Mao, Normand.
Statistical analysis: Chughtai, Mao, Normand, Sedrakyan.
Administrative, technical, or material support: Chughtai, Mao, Forde.
Conflict of Interest Disclosures: None reported.
Funding/Support: This work was supported by the Weill Cornell Medical College Male Health Center and Patient-Centered Comparative Effectiveness Program Medical Device Epidemiology Network Science and Infrastructure Center (Dr Sedrakyan). The center is a collaborative entity jointly funded by the US Food and Drug Administration and Weill Cornell Medical College’s Department of Urology, Division of Vascular and Endovascular Surgery in the Department of Surgery, and Department of Cardiothoracic Surgery to advance the comparative effectiveness, quality, and regulatory science for devices and surgical procedures. Dr Chughtai is a urologist and senior investigator at the center.
Role of the Funder/Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Previous Presentation: Preliminary results of this study were presented at the European Association of Urology Annual Meeting; March 14, 2016; Munich, Germany.