Federico Spelzini

The biology behind fascial defects and the use of implants in pelvic organ prolapse repair

Implant materials are increasingly being used in an effort to reduce recurrence after prolapse repair with native tissues. Surgeons should be aware of the biology behind both the disease as well as the host response to various implants. We will discuss insights into the biology behind hernia and abdominal fascial defects. Those lessons from “herniology” will, wherever possible, be applied to pelvic organ prolapse (POP) problems. Then we will deal with available animal models, for both the underlying disease and surgical repair. Then we will go over the features of implants and describe how the host responds to implantation. Methodology of such experiments will be briefly explained for the clinician not involved in experimentation. As we discuss the different materials available on the market, we will summarize some results of recent experiments by our group.

Tensile strength and host response towards silk and type I polypropylene implants used for augmentation of fascial repair in a rat model

Objective: We compared host response, architectural integration and tensile strength of two different macroporous silk constructs to a polypropylene type I implant in a rat model for augmentation of primary fascial defect repair. Materials and Methods: Animals were sacrificed on days 7, 14, 30 and 90 after implantation. The explants were evaluated macroscopically for infections, herniations and adhesions, mechanically for tensile strength, and histopathologically, to evaluate collagen deposition and inflammatory response. Results: The tensile strength of the explants showed a gradual increase for all materials. All implants uniformly shrank around one fifth by 90 days. In the silk implants, the inflammatory reaction showed a remarkable higher number of foreign body giant cells that characteristically spread from the periphery into implants. Collagen deposition was comparable for all the materials. In Silk a higher grade of neovascularisation was observed. Conclusion: Silk explants expressed high tensiometric strength, which was associated with a marked fibrotic process. The silk implants induced a strong foreign body reaction accompanied by microscopic signs of architectural degradation at 90 days. Polypropylene explants showed a more moderate foreign body reaction without architectural disturbance.

Porous Acellular Porcine Dermal Collagen Implants to Repair Fascial Defects in a Rat Model: Biomechanical Evaluation up to 180 Days

Aim: To investigate the biomechanical properties of porous collagen matrices in a rat abdominal wall defect model. Study Design: 112 rats were implanted with non-cross-linked InteXèn LP, cross-linked Pelvicol, and two investigational acellular collagen matrices (ACMs) sterilized either with ethylene oxide (ACM ETO) or γ-irradiation (ACM GI). After 14, 30, 90 and 180 days, 7 animals per group were sacrificed to document adhesions, herniation, infection, stress resistance and histology. Results: The 2 sterilization methods did not cause measurable differences between ACMs. Pelvicol was more resistant than ACMs but showed degradation at 90 days without loss of strength. InteXèn LP became remodeled as a thin fibrous scar and was more resistant at all time points; however, some animals developed bulging. Conclusions: Non-cross-linked InteXèn LP became remodeled by 180 days with remarkable stress resistance. Despite cross-linking Pelvicol showed degradation. Comparable but investigational ACM explants were less resistant without morphologic differences to explain this.

Is Occult Stress Urinary Incontinence a Reliable Predictive Marker

Objective Pelvic reconstructive surgery can be associated to correction, persistence, or onset of stress urinary incontinence. The aim of our study was to evaluate the incidence of stress incontinence (SI) after prolapse repair in 3 groups with different preoperative urodynamic findings and to find out the predictiveness of occult SI. Methods Patients undergoing vaginal hysterectomy, uterus-sacral ligament colposuspension, and traditional anterior repair for pelvic prolapse were retrospectively analyzed. No patient underwent any additional anti-incontinence procedure. Preoperative evaluation included clinical history, physical examination, and urodynamic assessment with a pessary reduction test. According to urodynamic findings, women were divided into SI (A), occult SI (B), and continence (C) groups. Primary outcome was to compare the incidence of postoperative SI among groups. Secondary outcome was to assess postoperative quality of life with International Consultation on Incontinence questionnaire-short form questionnaire. Results One hundred fifty patients were analyzed (A: n = 30; B: n = 43; C: n = 77). Mean follow-up was 18.4 ± 0.9 months without differences among groups. Patients in group B did not have higher postoperative SI rate compared to group C. There were no differences in International Consultation on Incontinence questionnaire-short form scores in symptomatic women among groups. Conclusions In our series, occult stress urinary incontinence is a poor urodynamic marker to predict the development of postoperative SI.

Outcomes of Transvaginal High Uterosacral Ligaments Suspension: Over 500-Patient Single-Center Study

Background Uterosacral ligament (USL) suspension is a safe and effective procedure in terms of anatomical, functional, and subjective outcomes for primary surgical treatment of prolapse. Objectives There has been a renewed interest toward native tissue prolapse repair by vaginal route because of low cost and lack of mesh-related complications. Uterosacral ligaments are considered safe, effective, and durable as suspending structures for primary surgical repair of the apical compartment. Our aim was to evaluate complications, anatomical, functional and subjective outcomes of high USL suspension for primary prolapse repair. Methods Data of patients who underwent vaginal hysterectomy followed by high USL suspension for pelvic organ prolapse were retrospectively analyzed. Operative data, as well as complications, were recorded. Anatomical recurrence was defined as descent of any compartment stage II or greater according to the Pelvic Organ Prolapse Quantification system. Functional outcomes focused on urinary, bowel, and sexual dysfunctions. International Consultation on Incontinence Questionnaire–Urinary Incontinence Short Form, Wexner, and Patient Global Impression of Improvement questionnaires were collected. Results Data of 533 women were analyzed. Mean follow-up was 32 (SD, 19) months (dropout rate, 2.6%). Most frequent complication was ureteral kinking (2.6%). Total recurrence rate was 13.7%, with anterior compartment being the most frequent (9.4%), whereas reoperation for symptomatic prolapse recurrence was required in only 1% of patients. Improvement of urinary incontinence, voiding dysfunction, constipation, and dyspareunia was observed. Overall subjective satisfaction was high (Patient Global Impression of Improvement score, 1.3), ranging from “much improved” to “very much improved.” Conclusions Uterosacral ligament suspension is a safe and effective procedure in primary surgical treatment of pelvic organ prolapse. Anatomical, functional, and subjective outcomes were very satisfactory, and reoperation rate for recurrence was only 1%.

Different stages of pelvic prolapse: morphologic and biochemical analysis of anterior vaginal wall

Collagen is ubiquitous in the human body and it is the main component of connective tissue. Collagen is also the principal component of endopelvic fascia and it is involved in the physiopathology of female organ prolapse (POP). The role of collagen in the physiopathology of POP has been studied with conflicting results, being difficult to distinguish the cause from the effect and to standardize the samples. The turnover of connective tissue in the vaginal wall is an important process both in healthy women and in women with prolapse. MMP-1, MMP-8 and MMP-13 specifically cleave native triple collagen (I, II, III) helix, yelding two fragments. These fragments are subject to gelatinase (MMP-2 and MMP-9) degradation. MMP-2 and MMP-9 activity, may be regulated at different levels (trascriptional and activation level) influencing the amount of collagen. Aim of this study is to find a correlation between staging of anterior vaginal wall prolapse and morphologic and biochemical (MMP-2 and MMP-9 amount) features of anterior vaginal wall. Anterior vaginal wall full thickness biopsies (eightyfive patients) including endopelvic fascia have been collected during surgical procedures. Recurrence or vault prolapse have been ruled out. POP samples have been classified according to POP-Quantification and they have been divided in three groups: group A (controls), group B (I and II stage prolapse) and group C (III and IV stage prolapse). Each sample has been processed for both microscopic and zymography analysis. Formalin fixed samples have been embedded, cut and stained with Trichromic Masson Goldner (TMG) stains. Microscopic analysis have been performed to evaluate collagen amount, collagen organization, and to assess muscular component. All parameters have been scored semi-quantitatively by two blind observers on vaginal mucosa and underlying fascia. MMP-2 and MMP-9 activity have been evaluated by gelatine zymography. Statistical evaluation have been made by One-Way ANOVA analysis of variance. An increase in collagen content and a better connective organization in women with prolapse greater than III stage (group C p<0.05) is demonstrated. Moreover a significant decrease in MMP-2 activity is evident in high stage prolapse if compared with controls (group C p<0.05). The data obtained suggest that high stage POP is correlated with a reduction of MMP-2 collagenic activity that determines an increase in collagen amount. Such observation correlates with the common finding of a subjectively thickened vaginal wall of patients affected by a III – IV stage (Group C)