Tissue integration and tolerance to meshes used in gynecologic surgery: an experimental study

OBJECTIVE: To evaluate the tissue integration of and tolerance to five different mesh types used in genital prolapse surgery to provide mechanical support. STUDY DESIGN: We placed five different meshes (Vicryl, Vypro, Prolene, Prolene soft, and Mersuture) on the peritoneums of 12 pigs. After 10 weeks, we used light microscopy to analyze the tissue integration of and tolerance to these meshes. We looked for inflammation, vascularization, fibroblasts, collagen fibers and the organization of connective tissue. RESULTS: The absorbable prostheses made of polyglactin 910 (Vicryl) and the non-absorbable prostheses made of polypropylene (Prolene and Prolene soft) induced the least severe inflammatory reactions. Tissue integration was best with the polypropylene meshes, which allowed the development of a well-organized, fibrous, mature, connective tissue. CONCLUSION: The tissue response to prosthetic meshes depends on the material used and its structure. This work highlights the feasibility of carrying out experimental studies to test the tolerance to and integration of biomaterials used in gynecology. Such studies need to be carried out whenever new prostheses become available to validate their use in common practice.     

The Mersilene mesh suburethral sling: A clinical and urodynamic evaluation

OBJECTIVES: Our purpose was to determine the efficacy and safety of the Mersilene (Ethicon, Inc., Somerville, N.J.) mesh sling.STUDY DESIGN: A total of 110 women diagnosed at the University of Massachusetts Medical Center with recurrent genuine stress incontinence, low-pressure urethra, or chronically increased intraabdominal pressure underwent a Mersilene mesh sling procedure. The women were followed up with yearly clinical and 1-year urodynamic evaluations. Sixty-seven patients had both preoperative and postoperative complete urodynamic evaluations. Paired t test was used except where stated.RESULTS: Seventy-nine of 83 patients (95%) who were examined at a mean of 15 months reported complete stress continence. Objective cure rate (n = 72) by 1-year postoperative stress test was 93%. The pressure transmission ratio increased from 75% to 112% (p < 0.0001). The mean number of days to normal voiding was 10. Three women have long-term difficulty with retention. Erosion of the vaginal sling site occurred in two women, one of whom required removal (0.9%).CONCLUSIONS: The suburethral sling with Mersilene mesh is a safe, effective treatment for specific types of genuine stress incontinence on the basis of yearly clinical and 1-year urodynamic follow-up, and it demonstrates a low rejection rate.     

A comparative study of laparoscopic sacrocolpopexy and total vaginal mesh procedure using lightweight polypropylene meshes for prolapse repair

ObjectiveUse of vaginal meshes for treatment of pelvic organ prolapse (POP) remains controversial. A trend toward abdominal approaches and the development of new meshes has been noted. We compared the 1-year results of two different approaches using new lightweight meshes.Materials and methodsSixty-nine (95.8%) of 72 women with POP Stage ≥ 2, who underwent laparoscopic sacrocolpopexy (LSC) (n = 39) or a total vaginal mesh (TVM) procedure (n = 30) using lightweight polypropylene meshes, were studied. Baseline and follow-up assessments included a pelvic examination and a composite condition-specific questionnaire. A detailed comparison of 1-year outcomes was made. Data were analyzed using appropriate statistical methods.ResultsCompared to the TVM group, the LSC group was characterized by a younger age (53.7 years vs. 64.1 years, p < 0.001) and a longer operating time (264 minutes vs. 177.6 minutes, p < 0.001). Objective anatomic success (POP Stage ≤ 1) rates were similar between groups after statistical adjustment, i.e., 84.6% (33/39) and 86.7% (26/30) after LSC and TVM (p = 0.94), respectively. However, the dominant recurrence sites were different with anterior (n = 6) most frequent after LSC and apical (n = 4) most frequent after TVM. Reoperations were needed for the four (13.3%) apical recurrences in the TVM group. No serious complications were noted. We found “cystocele as the dominant prolapse” (p = 0.016; odds ratio = 6.94) and “suspension of prolapsed (POP Stage ≥ 2) uterus” (p = 0.025; odds ratio = 7.00) significantly affected recurrence after LSC and TVM, respectively.ConclusionPOP repair by LSC or TVM using the new lightweight polypropylene meshes seems to be safe and has comparable outcomes, but limitations may vary.     

Advanced utero-vaginal prolapse and vaginal vault suspension: synthetic mesh vs native tissue repair

Purpose

To compare prosthetic and ligament vaginal vault suspension at vaginal hysterectomy in patients, with utero-vaginal stage III–IV pelvic organ prolapse quantification.

Methods

A retrospective case–control study was designed to compare 61 patients who had undergone Posterior intravaginal slingplasty (PIVS) with 61 patients in a matched control group who had undergone uterosacral ligament suspension (ULS). The primary outcome was to compare anatomic vaginal vault failure rate. The secondary outcomes were subjective cure and cure without adverse events.

Results

Follow-up mean duration for the PIVS and ULS groups was 56.2 and 57.7 months, respectively. Recurrent vault prolapse was observed more frequently in the ULS group with pre-intervention stage IV prolapse (0 vs 14.8 %; p = 0.04), while there was no difference in prolapse recurrence at any vaginal site. Although the subjective cure of PIVS and ULS was superimposable (91.8 vs 86.9 %; p = 0.25), there was a significantly higher cure rate, without adverse events, in the ULS group (90.2 vs 100 %; p = 0.01).

Conclusions

Non-mesh vaginal vault repair should be considered the first-line measure at vaginal hysterectomy; prosthetic repair should be used for therapeutic purposes in patients with vaginal vault recurrence and considered at vaginal hysterectomy only in selected subjects with complete utero-vaginal eversion.     

Tissue effects of and host response to human papillomavirus infection

Human papillomaviruses are a heterogeneous group of DNA tumor viruses associated with hyperplastic (warts, condylomas), dysplastic (CIN and VIN), and malignant lesions (carcinomas) of squamous epithelium. Each HPV type is preferentially associated with specific clinical lesions and has an anatomic site preference for either cutaneous or mucosal squamous epithelium. Infection appears to begin in the basal cells. Early gene expression is associated with acanthosis, and late gene expression is associated with appearance of structural antigens and virions in nuclei of cells of the granular layer, usually koilocytotic cells. Malignant transformation of warts and papillomas appears to be related to a variety of factors: (1) infection by certain HPV types (HPV-5, HPV-8, HPV-16, HPV-18, HPV-31); (2) decreased cellular immunity to HPV-associated antigens; and (3) interaction with cofactors, such as other microorganisms or sunlight (see also the article by Kashima and Shah). Spontaneous regression or successful treatment of the benign lesions appears to depend on either naturally acquired or iatrogenically related stimulation of HPV type-specific immunity. The humoral antibody response to HPV particles may be important in preventing infection. In contrast, the local events surrounding regression of warts and condylomas are primarily associated with specific cell-mediated immunity. Local cell-mediated immune responses, particularly cell-associated soluble mediators and stationary macrophage-like cells, may be especially important in the host's immune response to mucosal infections.     

Gestational effects on host inflammatory response in normal and pre-eclamptic pregnancies

Objective

Pre-eclampsia (PET) remains a leading cause of maternal and neonatal morbidity and mortality. Although its pathophysiology involves an underlying inflammatory dysfunction, it is unclear how this may be affected by increasing gestational age, particularly in relation to the time of onset of disease. Murine studies have indicated that a progressive increase in serum inflammatory profile is a physiological feature of normal gestation. The present study aimed to investigate this phenomenon in women in relation to normal and pre-eclamptic pregnancies.

Study design

Control and PET groups (each n = 20) were divided into early and late pregnancy (before and after 34 weeks gestation, respectively). Whole blood was diluted 1:1 with RPMI 1640 medium with/without 1 μg/ml lipopolysaccharide at 37 °C for 24 h under a humidified 5% CO₂ atmosphere. Samples were collected at 0, 2, 6 and 24 h and analysed for interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 (p70), IL-13, IL-17, granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), interferon (IFN)-γ, monocyte chemotactic protein (MCP-1), macrophage inflammatory protein (MIP)-1β and tumour necrosis factor (TNF)-α by fluid-phase multiplex immunoassay.

Results

This study confirms that pregnancy features an increasing inflammatory response with advancing gestational age, which was seen in both control and PET pregnancies (P < 0.01).

Conclusions

This increase in inflammatory responsiveness with advancing gestation may provide an explanation for the incidence of late onset PET in the absence of placental pathology, as well as serving as a potential physiological priming mechanism geared towards increasing maternal sensitivity to the fetal triggers of labour.     

Histologic correlates of virulence in ovarian adenocarcinoma: II. Morphologic correlates of host response

Original histologic slides were reviewed from 87 patients with advanced ovarian carcinoma, all of whom had been treated with cisplatin, alone or in combination. The degree of lymphocyte infiltration in the tumor was not related to histologic or cytologic tumor differentiation. However, the degree of lymphocyte infiltration was related to improved survival.     

Laparoscopic removal of endometriomas: sonographic evaluation of residual functioning ovarian tissue

OBJECTIVE: The aim of this study was to determine whether and to what extent laparoscopic removal of ovarian endometriotic cysts is a tissue-sparing procedure. STUDY DESIGN: At the University Hospital, 77 women of reproductive age with endometriomas and 55 with dermoid cysts underwent laparoscopic removal of the ovarian disease by stripping. Within 1 month before and within 36 months after surgery all patients underwent transvaginal sonographic evaluation of ovarian volume of the endometriomas or dermoid cysts and measurement of the residual ovarian tissue. RESULTS: The residual ovarian volume after surgery was significantly less for the endometrioma group than for the dermoid group. Comparison of the volume of the treated ovary with that of the untreated contralateral ovary showed a significant difference (4.3+/-2.3 cm(3) vs 9.7+/-3.9 cm(3)) only in the endometrioma group. CONCLUSION: Ovarian stripping of endometriomas, but not of ovarian dermoids, is associated with a significant decrease in residual ovarian volume which may result in diminished ovarian reserve and function.     

Sexual function following trocar-guided mesh or vaginal native tissue repair in recurrent prolapse: a randomized controlled trial

IntroductionSurgical treatment of pelvic organ prolapse (POP) affects sexual function. Generally, this results in improved sexual function, but deterioration is reported also.AimThe purpose of this study was to evaluate and compare sexual function in patients with recurrent POP undergoing either a vaginal surgical repair with native tissue or a trocar‐guided mesh insertion.MethodsSexually active patients randomly assigned to either native tissue repair or trocar‐guided mesh insertion, which had completed the pelvic organ prolapse (POP)/urinary incontinence sexual questionnaire (PISQ‐12) both at baseline and at 12 months, were included. Total, subscale, and individual question analysis were performed. Logistic regression was used to identify factors that were independently associated with improvement/deterioration in total PISQ‐12 scores.Main Outcome MeasuresPrimary outcome was sexual function at 12 months following surgery, measured by the short form of the pelvic organ prolapse/urinary incontinence sexual questionnaire (PISQ‐12). Secondary outcomes were the identification of factors independently associated with change in PISQ‐12 scores and changes in individual PISQ‐12 question scores.ResultsSixty patients were included; 32 in the mesh arm and 28 in the native tissue arm. At 12 months, PISQ‐12 scores were not different in both treatment arms (34.3, standard deviation [SD] 6.7 vs. 34.7, SD 5.7), but improvement was detected in the native tissue arm, whereas PISQ‐12 total score remained unchanged in the mesh arm. Deteriorations were observed in the behavioral/emotive subscale and partner‐related items in the mesh arm. In the native tissue arm, significant improvements in the physical and partner‐related subscales were observed. The presence of mesh exposure was independently associated with deterioration in total PISQ‐12 score.ConclusionAt 12 months, PISQ‐12 scores were not different in either treatment arm, but were affected differently by trocar‐guided mesh insertion or by native tissue repair. Mesh exposure was independently associated with deterioration in sexual function. Milani AL, Withagen MIJ, The HS, Nedelcu‐van der Wijk I, and Vierhout ME. Sexual function following trocar‐guided mesh or vaginal native tissue repair in recurrent prolapse: A randomized controlled trial. J Sex Med 2011;8:2944–2953.     

Ovarian tissue banking and fertility preservation in cancer patients: histological and immunohistochemical evaluation

OBJECTIVE: A combination of chemotherapy and radiotherapy in young females with cancer has greatly enhanced the life expectancy of these patients, even if these treatments have a highly deleterious effect on the ovary and cause a severe depletion of the follicular store. Cryopreservation of ovarian tissue before chemotherapy and/or radiotherapy, followed by autograft after remission or in in vitro maturation, could restore gonadal function and fertility. The aim of this study is to verify the efficiency of the ovarian tissue cryopreservation procedure by histological and immunohistochemical analyses. METHODS: Ovarian tissue was obtained by laparoscopy from 22 patients affected with different malignant diseases. Tissue specimens were frozen using a combination of PROH (1,2-propanediol) and sucrose as cryoprotectants, and the cryopreservation protocol used consisted of a slow freezing-rapid thawing program. Both fresh and frozen/thawed tissues were embedded in paraffin blocks for histological and immunohistochemical analyses. RESULTS: Good stromal and follicular morphology was found in fresh and frozen/thawed tissue. No significant differences were found in follicular density, distribution, and diameters in fresh and frozen/thawed tissue. Follicle immunohistochemical analysis showed a high percentage of negative staining for both estrogen receptor (ER) (100% both in fresh and frozen/thawed specimens) and progesterone receptor (PR) (97% versus 91%, respectively). Regarding the Ki67 protein, positive staining was found in both the granulosa cells and/or the oocytes (36% in fresh and 56% in frozen/thawed). For the Bcl2 protein, positive staining was observed in the follicle granulosa cells but not in the oocytes in 74% of the fresh and in 79% of the frozen/thawed specimens. For the stromal cells, ER showed a negative staining distribution in 97% of the fresh and 100% of the frozen/thawed specimens. The stroma staining distribution was diffuse/focal in fresh versus frozen/thawed specimens (50% versus 74% respectively) for PR, patch/focal (70% versus 80%, respectively) for Ki67 protein, and diffuse (55% versus 54%, respectively) for Bcl2. CONCLUSIONS: These results suggest that human ovarian tissue morphology, antigenicity, cellular proliferation, and anti-apoptotic index were well preserved by cryopreservation in PROH and sucrose.     

Pulsed estrogen exposure selectively modulates tissue response: a hypothesis.

All postmenopausal hormone replacement therapies (HTs) aim to provide a steady mid-follicular serum concentration of estrogen, with the exception of pulsed estrogen therapy, which concentrates hormone exposure in the few hours following administration. This alteration in the kinetics of estradiol exposure does not change the beneficial effect of HT on climacteric symptoms or bone loss, but does reduce the stimulation of the breast and uterus leading to less mastalgia and bleeding. The following hypothesis provides a plausible pharmacological explanation as to how estradiol kinetics can selectively modify tissue response. Pulsed estradiol exposure influences the relative abundance of estrogen receptors (ERs) alpha and beta, via a tissue-dependent non-genomic signaling pathway, resulting in selective upregulation and activation of ERbeta in breast and endometrium, but not in bone. In addition, pulsed estrogen exposure also increases local concentration of 2-methoxyestradiol, a specific estradiol metabolite with proven anti-tumor properties.