Occhino, John A.

Objective The aim of the study was to compare vaginal wound healing after exosome injection in a porcine mesh exposure model with (1) single versus multiple dose regimens and (2) acute versus subacute exposure. Methods Six 80-kg Yorkshire-crossed swine each had 2 polypropylene meshes implanted to create the vaginal mesh exposure model. Animals were divided into 3 groups based on number and timing of exosome injection: (1) single purified exosome product (PEP) injection (acute-single), (2) weekly PEP injections (acute-weekly, 4 total injections), and (3) delayed single injection (subacute-single). Acute and subacute injections occurred 1 and 8 weeks after mesh implantation, respectively. EdU, a thymidine analog, was given twice weekly after the first injection to track tissue regeneration. Euthanasia and tissue analysis occurred 4 weeks after the first injection. ImageJ was used to quantify epithelial thickness, cellular proliferation, and capillary density. Statistical analysis was performed using analysis of variance and post hoc Tukey test. Results Acute-single PEP injection tissues mirrored pilot study results, validating replication of protocol. Within the acute groups, weekly dosing resulted in 1.5× higher epithelial thickness (nonsignificant), 1.8× higher epithelial proliferation ( P < 0.05), and 1.5× higher regenerated capillary density ( P < 0.05) compared with single injection. Regarding chronicity of the exposure, the subacute group showed 1.7× higher epithelial proliferation (nonsignificant) and similar capillary density and epithelial thickness as compared with the acute group. Conclusions Exosome redosing resulted in significantly greater epithelial proliferation with significantly higher regenerated capillary density, leading to a trend toward thicker epithelium. Subacute exposure exhibited similar regeneration to acute exposure despite a delayed injection timeline. These results contribute to a growing body of preclinical research demonstrating utility of exosomes in pelvic floor disorders.

Objectives The purpose of this study was to explore the utility of an injectable purified exosome product derived from human apheresis blood to (1) augment surgical closure of vaginal mesh exposures, and (2) serve as a stand-alone therapy for vaginal mesh exposure. Methods Sixteen polypropylene meshes (1×1–3×3 cm) were implanted in the vaginas of 7 Yorkshire-crossed pigs by urogynecologic surgeons (day 0). On day 7, group 1 underwent surgical intervention via vaginal tissue suture reclosure with (n=2 pigs, n=4 meshes) or without (n=2 pigs, n=4 meshes) exosome injection; group 2 underwent medical intervention with an exosome injection (n=3, n=8 meshes). One animal in group 2 was given oral 2′-deoxy-5-ethynyluridine to track cellular regeneration. Euthansia occurred at 5 weeks. Results Mesh exposures treated with surgical closure alone experienced reexposure of the mesh. Exosome treatment with or without surgical closure resulted in partial to full mesh exposure resolution up to 3×3 cm. Exosome-treated tissues had significantly thicker regenerated epithelial tissue (208 μm exosomes-only and 217 μm surgery+exosomes, versus 80 μm for surgery-only; P < 0.05); evaluation of 2′-deoxy-5-ethynyluridine confirmed de novo regeneration throughout the epithelium and underlying tissues. Capillary density was significantly higher in the surgery+exosomes group ( P = 0.03). Surgery-only tissues had a higher inflammatory and fibrosis response as compared with exosome-treated tissues. Conclusions In this pilot study, exosome treatment augmented healing in the setting of vaginal mesh exposure, reducing the incidence of mesh reexposure after suture closure and decreasing the area of mesh exposure through de novo tissue regeneration after exosome injection only. Further study of varied local tissue conditions and mesh configurations is warranted.

Objective To compare the perioperative outcomes of transvaginal/perineal and abdominal approaches to rectovaginal fistula (RVF) repair using a national multicenter cohort. Methods The American College of Surgeons National Surgical Quality Improvement Program database was utilized to identify women undergoing RVF repair from 2005 to 2016. Emergent cases and those with concomitant bowel diversion were excluded. Baseline patient demographics, procedure characteristics, 30-day postoperative complications, return to the operating room, and readmission were evaluated. Baseline characteristics were compared across surgical approach. Multivariable logistic regression models identified preoperative characteristics independently associated with postoperative complications. Results A total of 2288 women underwent RVF repair: 1560 (68.2%) via transvaginal/perineal approach and 728 (31.8%) via abdominal approach. Patients undergoing transvaginal/perineal repair were significantly younger (median age, 46 years vs 63 years), with lower American Society for Anesthesiologist (ASA) scores, and less frequency of diabetes mellitus, dyspnea, severe chronic obstructive pulmonary disease, hypertension, disseminated cancer, and bleeding disorders (all P < 0.01). Those undergoing abdominal repair had higher rates of major complications (25.8% vs 8.7%), minor complications (13.5% vs 6.3%), and readmission (13.2% vs 7.8%). On multivariable analyses, ASA Class 3/4, disseminated cancer, and hematocrit <30% ( P < 0.01) were associated with major complications in both groups. Conclusions Patients undergoing RVF repair via abdominal approach were older with more comorbidities and had higher postoperative complications rates, likely secondary to underlying differences in the treated populations. Irrespective of surgical approach, ASA class, disseminated cancer, and preoperative anemia were associated with higher postoperative morbidity. This may enhance preoperative counseling and allow for careful patient selection.

Objectives The objective of this study was to evaluate perioperative complications in women who underwent minimally invasive sacrocolpopexy (MISC) versus mesh-augmented vaginal repair (vaginal mesh) for pelvic organ prolapse. Methods We identified patients undergoing MISC and vaginal mesh via Current Procedural Terminology codes from the American College of Surgeons National Surgical Quality Improvement Program database from 2005 to 2016. Those undergoing concomitant hysterectomy were excluded. Univariate analyses were performed to compare baseline characteristics and 30-day complications. Multivariable logistic regression models were constructed to assess the association between surgical approach and complications, prolonged hospitalization, reoperation, and blood transfusion. A multivariable Cox proportional hazard model was used to evaluate hospital readmission. Results A total of 5722 patients were identified (2573 MISC [45%], 3149 vaginal mesh [55%]). Those undergoing MISC repairs had a significantly lower rate of urinary tract infection (3.1 vs 4.2%; P = 0.03) and blood transfusion (0.5 vs 1.4%; P < 0.001). There was no difference in reoperation rate (1.3 vs 1.6%; P = 0.35). Multivariable analysis showed no significant association of MISC with overall (odds ratio [OR], 0.91; P = 0.44), major (OR, 1.30; P = 0.31), or minor complication (OR, 0.85; P = 0.26). There were lower odds of receiving a blood transfusion (OR, 0.44; P = 0.02) and higher odds of prolonged hospitalization (>2 days; OR, 1.47; P = 0.003) for the MISC group. There was no difference in reoperation (OR, 0.79; P = 0.38) or hospital readmissions (hazard ratio, 1.25, P = 0.32). Conclusions Minimally invasive sacrocolpopexy was associated with a lower rate of blood transfusion than transvaginal mesh placement. There was no significant difference in 30-day complication rates, reoperation, or readmission between these prolapse procedures when performed without concomitant hysterectomy.

Objective The aim of this study was to compare the perioperative morbidity of minimally invasive sacrocolpopexy (MISC) and nonmesh apical vaginal surgeries for repair of vaginal vault prolapse using data from a contemporary nationwide cohort. Methods The American College of Surgeons' National Surgical Quality Improvement Program database was used to identify women who underwent apical prolapse surgery via vaginal approach or MISC from 2010 to 2016. Those undergoing concomitant hysterectomy or transvaginal mesh placement were excluded. Associations of surgical approach with 30-day complications, prolonged hospitalization, and reoperation were evaluated using logistic regression. Readmission within 30 days was calculated using the person-years method and Cox proportional hazards models. Results Overall, 6390 women underwent surgery, including 3852 (60%) via vaginal approach and 2538 (40%) via MISC. Patients undergoing MISC were younger ( P < 0.0001) and less likely to have hypertension ( P = 0.04) or chronic obstructive pulmonary disease ( P = 0.008), with lower American Society of Anesthesiologists scores ( P < 0.0001) and higher preoperative hematocrit ( P = 0.009). The MISC cohort had a lower unadjusted rates of minor complications (3.9% vs 5.6%; P = 0.004), urinary tract infection (3.3% vs 4.8%; P = 0.004), and prolonged hospitalization (5.2% vs 7.9%; P < 0.0001), with a higher rate of nephrologic ( P = 0.01) complications. On multivariable analysis, there were no significant associations of MISC with the risk of 30-day complications (odds ratio [OR], 1.51; 95% confidence interval [CI], 0.92–2.51; P = 0.11), prolonged hospitalization (OR, 0.96; 95% CI, 0.76–1.21; P = 0.72), readmission (HR 1.03; 95% CI, 0.71–1.49; P = 0.88), or reoperation (OR, 0.95; 95% CI, 0.57–1.60; P = 0.86). Conclusions Minimally invasive sacrocolpopexy is associated with similar rates of 30-day complications, prolonged hospitalization, readmission, and reoperation compared with nonmesh vaginal surgeries for apical prolapse.

A wide variety of fistulae occur in the female pelvis, most of which cause significant morbidity. Diagnosis, characterization, and treatment planning may be difficult using traditional imaging modalities such as fluoroscopy and computed tomography. To date, there is no comprehensive literature review of the radiologic findings associated with various types of female pelvic fistulae, and furthermore, none dedicated to magnetic resonance imaging (MRI). In this article, we seek to provide a broad overview of the MRI characteristics of female pelvic fistulizing disease in combination with epidemiologic and clinical characteristics. MRI is often considered the imaging modality of choice for evaluation of fistulae owing to its superior soft‐tissue contrast and ability to provide surgeons with the highest quality information derived from just one study, including anatomic location of fistulae and associated pelvic pathology. In other instances, MRI can be complementary to the more traditional imaging techniques. This review will describe the etiology, anatomy, MRI findings, and treatment pearls for several of the more common pelvic fistulae found in female patients, including anovaginal, rectovaginal, colovaginal, vesicovaginal, colovesical, and other complex fistulae.Level of Evidence: 5Technical Efficacy: Stage 3J. Magn. Reson. Imaging 2018;47:1172–1184