Effect of gelatin methacryloyl hydrogel on healing of the guinea pig vaginal wall with or without mesh augmentation.

INTRODUCTION AND HYPOTHESIS: The aims of this study were to evaluate the effectiveness of gelatin methacryloyl as an adjunct to anterior vaginal wall injury with or without vaginal mesh compared with traditional repair with suture. METHODS: Virginal cycling Hartley strain guinea pigs (n = 60) were randomized to undergo surgical injury and repair using either polyglactin 910 suture or gelatin methacryloyl for epithelium re-approximation or anterior colporrhaphy with mesh augmentation using either polyglactin 910 suture or gelatin methacryloyl for mesh fixation and epithelium re-approximation. Noninjured controls (n = 5) were also evaluated. After 4 days, 4 weeks, or 3 months, tissues were analyzed by hematoxylin & eosin in addition to immunolabeling for macrophages, leukocytes, smooth muscle, and fibroblasts. RESULTS: Surgical injury repaired with suture was associated with increased inflammation and vessel density compared with gelatin methacryloyl. Vimentin and α-smooth muscle actin expression were increased with gelatin methacryloyl at 4 days (p = 0.0026, p = 0.0272). There were no differences in changes in smooth muscle or overall histomorphology after 3 months between the two closure techniques. Mesh repair with suture was also associated with increased inflammation and vessel density relative to gelatin methacryloyl. Quantification of collagen content by picrosirius red staining revealed increased thick collagen fibers throughout the implanted mesh with gelatin methacryloyl compared with suture at 4 weeks (0.62 ± 0.01 µm2 vs 0.55 ± 0.01, p = 0.018). Even at the long-term time point of 3 months, mesh repair with suture resulted in a profibrotic encapsulation of the mesh fibers, which was minimal with gelatin methacryloyl. Smooth muscle density was suppressed after mesh implantation returning to baseline levels at 3 months regardless of fixation with suture or gelatin methacryloyl. CONCLUSIONS: These results suggest that gelatin methacryloyl might be a safe alternative to suture for epithelium re-approximation and anchoring of prolapse meshes to the vagina and may improve chronic inflammation in the vaginal wall associated with mesh complications.

Assessing patients' preferences for gender, age, and experience of their urogynecologic provider.

INTRODUCTION AND HYPOTHESIS: Understanding patient preferences regarding provider characteristics is an under-explored area in urogynecology. This study aims to describe patient preferences for urogynecologic care, including provider gender, age, experience, and presence of medical trainees. METHODS: This was a multicenter, cross-sectional, survey-based study assessing patient preferences with a voluntary, self-administered, anonymous questionnaire prior to their first urogynecology consult. A 5-point Likert scale addressing provider gender, age, experience, and presence of trainees was used. Descriptive statistics summarized patient characteristics and provider preferences. Chi-squared (or Fisher's exact) test was used to test for associations. RESULTS: Six hundred fifteen women participated from eight sites including all geographic regions across the US; 70.8% identified as white with mean age of 58.5 ± 14.2 years. Urinary incontinence was the most commonly reported symptom (45.9%); 51.4% saw a female provider. The majority of patients saw a provider 45-60 years old (42.8%) with > 15 years' experience (60.9%). Sixty-five percent of patients preferred a female provider; 10% preferred a male provider. Sixteen percent preferred a provider < 45 years old, 36% preferred 45-60 years old, and 11% of patients preferred a provider > 60 years old. Most patients preferred a provider with 5-15 or > 15 years' experience (49% and 46%, respectively). Eleven percent preferred the presence of trainees while 24% preferred trainee absence. CONCLUSION: Patient preferences regarding urogynecologic providers included female gender and provider age 45-60 years old with > 5 years' experience. Further study is needed to identify qualitative components associated with these preferences.

Anatomy, histology, and nerve density of clitoris and associated structures: clinical applications to vulvar surgery.

BACKGROUND: A precise understanding of structures comprising the female external genitalia is essential in obstetric and gynecologic practice. OBJECTIVE: To further characterize the anatomy, histology, and nerve density of the clitoris and associated structures, and to provide clinical correlations to vulvar surgery. MATERIALS AND METHODS: Unembalmed female cadavers were examined. The length and width of the body, glans, and crura of the clitoris were measured. Distances from the glans to the urethra and from the dorsal surface of the clitoral body to the mid pubic arch were recorded. The path of the dorsal nerve of the clitoris was examined, and the nerve width was measured as it emerged from the lateral surface of crura and at the distal clitoral body. Distances from where the dorsal nerve emerged from the perineal membrane to the posterior surface of the membrane and to mid pubic arch were measured. Connective tissue layers associated with the clitoris were examined. Tissue was harvested from additional unembalmed cadavers, and nerve density of the labia minora, glans, and clitoral body were analyzed. Histological examination was performed on vulvar structures to clarify tissue composition. Descriptive statistics were used for data analyses. RESULTS: A total of 27 cadavers (aged 48-96 years) were examined, 22 grossly and 5 histologically. The median length and width of clitoral body were 29 mm (range, 13-59 mm) and 9 mm (range, 5-14 mm), respectively. The glans was 8 mm (range, 5-12 mm) long and 4 mm (range, 3-10 mm) wide. The length of the crura was 50 mm (range, 25-68 mm), and the width at the anterior portion was 9 mm (range, 2-13 mm). The closest distance from the glans to the urethra was 25 mm (range, 14-37 mm) and from the clitoral body to the mid pubic arch was 29 mm (range, 14-46 mm). The widths of the dorsal nerve at the lateral crura and at the distal clitoral body were 3 mm (range, 2-4 mm) and 1 mm (range, 1-2 mm), respectively. The distance from the dorsal nerve as it emerged from the perineal membrane to the mid pubic arch was 34 mm (range, 20-48 mm) and to the posterior surface of the membrane was 20 mm (range, 8-31 mm). The dorsal nerve and artery of the clitoris coursed adjacent to the medial surface of the inferior pubic ramus surrounded by a dense fibrous capsule adherent to the periosteum. The nerve and artery then coursed deep to dense connective tissue layers, which were contiguous with the suspensory ligament and fascia of the clitoris. Histologic examination revealed the presence of erectile tissue in the clitoral body, crura, and vestibular bulbs, but such tissue was absent in the glans and labia minora. Nerve density analysis revealed statistically significant greater density in the dorsal compared with ventral half of the clitoral body. Although not statistically significant, there was increased nerve density in the distal compared to the proximal half of the labia minora. CONCLUSION: Precise knowledge of clitoral anatomy and associated neurovascular structures is essential to safely complete partial vulvectomies, clitoral and vulvar reconstructive procedures, anti-incontinence surgeries, and repair of obstetric lacerations. Understanding the range of anatomic variations and awareness of the areas of increased nerve density is important during counseling and surgical planning. Although the dorsal nerve of the clitoris courses deep to dense connective tissue layers, inadvertent injury may occur in the setting of deep dissection or suture placement. The dorsal nerve seems most vulnerable with surgical entry or lacerations that extend from the midline of the prepuce to the inferior pubic rami.

Anatomic relationships of the pelvic autonomic nervous system in female cadavers: clinical applications to pelvic surgery.

BACKGROUND: The integrity of the pelvic autonomic nervous system is essential for proper bowel, bladder, and sexual function. OBJECTIVE: The purpose of this study was to characterize the anatomic path of the pelvic autonomic system and to examine relationships to clinically useful landmarks. STUDY DESIGN: Detailed dissections were performed in 17 female cadavers. Relationships of the superior hypogastric plexus to aortic bifurcation and midpoint of sacral promontory were examined; the length and width of plexus was documented. Path and width of right and left hypogastric nerves were recorded. The origin and course of the pelvic splanchnic nerves were documented. Individual nerve tissue that contributed to the inferior hypogastric plexus was noted. Relative position of nerves to arteries, viscera, and ligaments was documented. In a subset of specimens, biopsy specimens were obtained to confirm gross findings by histologic analysis. Descriptive statistics were used for data analyses and reporting. RESULTS: In all specimens, the superior hypogastric plexus was embedded in a connective tissue sheet within the presacral space, just below the peritoneum. In 14 of 17 specimens (82.4%), the plexus formed a median distance of 21.3 mm (range, 9-40 mm) below aortic bifurcation; in the remaining specimens, it formed a median distance of 25.3 mm (range, 20.5-30 mm) above bifurcation. In 58.8% of specimens, the superior hypogastric plexus was positioned to the left of midline. The median length and width of the plexus was 39.5 (range, 11.5-68) mm and 9 (range, 2.5-15) mm, respectively. A right and left hypogastric nerve was identified in all specimens and formed a median distance of 23 mm (range, 5-32 mm) below the promontory. The median width of the hypogastric nerve was 3.5 mm (range, 3-4.5 mm) on the right and 3.5 mm (range, 2-6.5 mm) on the left. The median distance from midportion of uterosacral ligament to the closest nerve branch was 0.5 mm (range, 0-4.5 mm) on right and 0 mm (range, 0-27.5 mm) on left. In all specimens, the inferior hypogastric plexus was formed by contributions from the hypogastric nerves and branches from S3 and S4. In 47.1% of hemipelvises, S2 branches contributed to the plexus. The sacral sympathetic trunk contributed to the plexus in 16 of 34 hemipelvises where this structure was identified. The inferior hypogastric plexus formed 1-3 cm lateral to the rectum and upper third of the vagina. From this plexus, 1-3 discrete branches coursed deep to the ureter toward the bladder. A uterine branch that coursed superficial to the ureter followed the ascending branch of the uterine artery. An S4 branch was found directly attaching to lateral walls of the rectum in 53% of specimens. Pelvic splanchnic nerves merged into the inferior hypogastric plexus on the lower and medial surface of the coccygeus muscle. Histologic analysis confirmed neural tissue in all tissues that were sampled. CONCLUSION: Anatomic variability and inability to visualize the small caliber fibers that comprise the inferior hypogastric plexus grossly likely underlines the reasons that some postoperative visceral and sexual dysfunction occur in spite of careful dissection and adequate surgical technique. These findings highlight the importance of a discussion with patients about the risks that are associated with interrupting autonomic fibers during the preoperative consent.

Comparisons of Functional Apical Support After Sacral Hysteropexy Versus Sacral Colpopexy: A Cadaveric Study.

OBJECTIVES: Prolapse procedures with uterine preservation offer an alternative to colpopexy with hysterectomy. Few studies have examined the differences in anatomic or subjective outcomes following sacral hysteropexy versus sacral colpopexy with hysterectomy. This study sought to compare the ability of sacral hysteropexy and sacral colpopexy with hysterectomy to resist downward traction as an estimate of apical support in human cadavers. METHODS: Sacral hysteropexy was performed on unembalmed female cadavers. A metal bolt/washer was threaded through the uterine fundus, down the cervical canal. and out the vagina and fastened to a waxed surgical filament, which ran over a fixed pulley at the table's end. Successive weights were added to provide increasing loads on the uterine fundus, and the distances traversed by the fundus were recorded. The same process was repeated after completion of a total hysterectomy (with vaginal cuff closure) and subsequent sacral colpopexy in the same specimen. Data were analyzed using paired-sample t test and repeated-measures analysis of variance (Sigma Plot version 13.0), with P ≤ 0.05 considered statistically significant. RESULTS: Eight female cadavers were utilized. With the addition of each weight, the average distance traversed by the uterine fundus or vaginal cuff gradually increased. There were no statistical differences in the distances moved by the apex between sacral hysteropexy and total hysterectomy/sacral colpopexy. CONCLUSIONS: These results suggest that functional support provided by sacral hysteropexy and sacral colpopexy with hysterectomy may be similar. Further studies are needed to correlate these findings with patient satisfaction, which may vary despite similar anatomic results.

Medial Thigh Anatomy in Female Cadavers: Clinical Applications to the Transobturator Midurethral Sling.

BACKGROUND: Mesh resection for refractory pain after transobturator midurethral sling may require exploration of structures different than those involved in insertion. Our objective was to describe the muscular and neurovascular anatomy of the medial thigh compartment. METHODS: Dissections were performed in unembalmed female cadavers. Relationships of medial thigh structures were evaluated relative to the midpubic arch and obturator nerve. An out-to-in transobturator tape was passed in a subset of cadavers, and its relationships to the obturator nerve and adductor muscles were examined. Descriptive statistics were used for analyses. RESULTS: Sixteen cadavers were examined. The adductor longus muscle was a median of 37 mm (26-50) from the midpubic arch with tendon length of 26 mm (12-53) and width of 16 mm (14-29). The gracilis was 21 mm (17-26) from the midpubic arch with tendon length of 28 mm (15-56) and width of 45 mm (31-68). The obturator nerve was 58 mm (51-63) from the midpubic arch with width of 5 mm (4-7). No differences between measurements in the supine and lithotomy positions were noted. The transobturator tape was 42 mm (30-47) from the midpubic arch, 36 mm (30-44) from the obturator nerve, and 20 mm (5-31) from the closest obturator nerve branch. The transobturator sling passed through the gracilis muscle in all specimens with variable passage through the adductors longus (75%) and brevis (25%). CONCLUSIONS: Familiarity with the medial thigh is essential for surgeons utilizing transobturator midurethral slings. Risks of mesh excision should be weighed against benefits before extensive thigh dissection for pain-related indications.

Gross and Histologic Anatomy of the Pelvic Ureter: Clinical Applications to Pelvic Surgery.

OBJECTIVE: To further evaluate relationships of the pelvic ureter to clinically relevant structures and to characterize the anatomy, histology, and nerve density of the distal ureter. METHODS: In this observational cadaveric study, 35 female cadavers were examined, 30 by gross dissections and five microscopically. Ureter length and segments of pelvic ureter were measured. Closest distances between the ureter and clinically relevant points were recorded. The distal pelvic ureter and surrounding parametrium were evaluated microscopically. Nerve density was analyzed using automated quantification of peripheral nerve immunostaining. Average measurements of nerve density in the anterior and posterior quadrants surrounding the ureter were statistically compared using a two-tailed t test. Descriptive statistics were used for analyses with distances reported as mean±SD (range). RESULTS: Gross dissections revealed ureter length of 26.3±1.4 (range 24-29) cm (right), 27.6±1.6 (25-30.5) cm (left). Lengths of ureter from pelvic brim to uterine artery crossover were 8.2±1.9 (4.4-11.5) cm (right), 8.5±1.5 (4.5-11.5) cm (left) and from crossover to bladder wall 3.3±0.7 (2.4-5.8) cm (right), 3.2±0.4 (2.6-4.1) cm (left). Intramural ureter length was 1.5±0.3 (1-2.2) cm (right) and 1.7±1.2 (0.8-2.5) cm (left). Distances from the ureter to uterine isthmus: median 1.7 (range 1-3.0) cm (right) and 1.7 (1.0-2.9) cm (left); lateral anterior vaginal fornix 1.5 (1.0-3.1) cm (right) and 1.7 (0.8-3.2) cm (left); lateral vaginal apex 1.3 (1.0-2.6) cm (right) and 1.2 (1.1-2.2) cm (left) were recorded. Microscopy demonstrated denser fibrovascularity posteromedial to the ureter. Peripheral nerve immunostaining revealed greater nerve density posterior to the distal ureter. CONCLUSION: Proximity of the ureter to the uterine isthmus and lateral anterior vagina mandates careful surgical technique and identification. The intricacy of tissue surrounding the distal ureter within the parametrium and the increased nerve density along the posterior distal ureter emphasizes the importance of avoiding extensive ureterolysis in this region.

Toll-like receptor 4 activation increases Akt phosphorylation in colon cancer cells.

BACKGROUND: Toll-like receptors (TLRs) are involved in innate immunity. Overexpression of TLRs has been implicated in various types of cancer including colorectal cancer (CRC). The phosphatidylinositol-3'-kinase (PI3K)/Akt signaling pathway is involved in CRC growth and progression. In this study, we determined whether TLR4 signaling and PI3K/Akt pathway activation occur in CRCs. MATERIALS AND METHODS: Human CRCs and adjacent mucosa were evaluated for TLR4 expression. CRC cell lines were treated with lipopolysaccharide (LPS), endogenous TLR4 ligand, to assess Akt phosphorylation. RESULTS: Human CRCs overexpressed TLR4 compared to matched normal mucosa. Additionally, TLR4 was expressed in CRC cells and LPS treatment increased Akt phosphorylation of TLR4-positive CRCs in a time-dependent manner. CONCLUSION: Our results identify TLR4 expression in human CRCs and activation of PI3K with LPS treatment. These findings suggest possible treatment strategies targeting TLR4 in CRC.