Boris Gabriel

Uterosacral ligament in postmenopausal women with or without pelvic organ prolapse

The uterosacral ligaments are thought to contribute to pelvic support. The objective of this study was to compare the structural components of these ligaments in women with and without pelvic organ prolapse (POP). We characterized uterosacral ligaments of 25 postmenopausal women with POP and 16 controls histomorphologically and immunohistochemically by quantifying their content of collagen I, III, and smooth muscle using a computerized image analysis. In 84% the uterosacral ligaments were composed of more than 20% of smooth muscle cells. There was no difference in collagen I expression and smooth muscle cell amount between women with POP and those without. In contrast, the collagen III expression was significantly related to the presence of POP (p<0.001) rather than age or parity. Our findings suggest that the higher collagen III expression might be a typical characteristic of POP patients’ connective tissue. The considerable amount of smooth muscle cells in uterosacral ligaments may provide pelvic support.

Increased expression of matrix metalloproteinase 2 in uterosacral ligaments is associated with pelvic organ prolapse

The uterosacral ligaments are an important part of the pelvic support system and connective tissue alterations are thought to contribute to the development of pelvic organ prolapse (POP). The objective of this study was to compare the expression of matrix metalloproteinases (MMPs) 1 and 2 in these ligaments in women with and without POP. We analyzed the tissue samples obtained from left and/or right uterosacral ligaments of 17 women with POP and 18 controls by immunohistochemistry. There was no difference in MMP-1 expression between women with POP and those without. In contrast, the MMP-2 expression was significantly related to the presence of POP (p=0.004) rather than to age or parity. There was no difference in MMP-1 and MMP-2 expression between left and right uterosacral ligaments in women with POP compared to controls. Our findings strongly indicate that increased MMP-2 expression in uterosacral ligaments is associated with POP.

Weak expression of focal adhesion kinase (pp125FAK) in patients with cervical cancer is associated with poor disease outcome.

Purpose: The pp125 focal adhesion kinase (FAK) plays a pivotal role in tumor cell signaling. FAK expression has been linked to tumor cell invasion and metastasis, but data on cervical cancer are inconclusive. Our goal was to investigate FAK expression in cervical cancer and to assess whether its expression correlates with prognosis. Experimental Design: FAK expression was examined using immunohistochemistry with sections from 162 resected cervical cancer specimens. Kaplan-Meier survival curves were used to determine the significance of FAK expression in the prognosis of cervical cancer patients. Results: Specific FAK expression was found in the tumor cells, whereas normal cervical epithelium showed barely any FAK expression. Of 162 invasive cervical cancer specimens, 55 (34%) revealed weak expression of FAK, whereas moderate and strong expression was found in 63 (39%) and 44 (27%) tumors, respectively. Patients with tumors expressing weak amounts of FAK were characterized by a significantly poorer overall survival compared with those with moderate and high intratumoral FAK expression (P = 0.002). Weak expression of FAK correlated with pelvic lymph node metastasis (P = 0.026) and recurrent disease (P = 0.013). Multivariate Cox regression analysis revealed decreased FAK expression and pelvic lymph node metastasis to be significant independent factors predictive of poor disease outcome (hazard ratio, 0.36; P = 0.005; hazard ratio, 2.38; P = 0.018, respectively). Conclusions: Weak expression of FAK in invasive cervical cancer is a strong independent predictor of poor patient outcome. Further studies are warranted to elucidate whether FAK expression analysis is a suitable tool identifying patients at high risk even at an early clinical stage.

Specific induction of pp125 focal adhesion kinase in human breast cancer.

The pp125 focal adhesion kinase (FAK) is involved in integrin-mediated cell signalling and overexpressed in a variety of solid tumours. Focal adhesion kinase expression has been correlated to invasion and metastasis, but the data on breast cancer are inconclusive. We analysed FAK mRNA, protein levels and expression patterns in primary breast cancer and normal breast tissue. FAK expression on the functional protein level and mRNA was determined in 55 matched pairs of breast cancer and corresponding normal tissue by Western blot, immunohistochemistry and RT–PCR. Using a score ranging from 0 to +5 for Western blots, we determined in normal breast tissue a score of 1.51±0.84 (mean±standard deviation), which was strongly induced to 2.91 (±1.22) in breast cancers (P<0.001). Overall, 45 out of 55 tissue pairs (81.8%) showed this upregulation of FAK protein in tumours in comparison to normal tissue. Immunohistochemistry confirmed these findings with a significant higher score for tumours vs physiological tissue (1.0±0.63 vs 2.27±0.91; P=0.001). Interestingly, no overall significant difference in the mRNA levels (P=0.359) was observed. In conclusion, expression levels of the FAK protein are specifically upregulated in breast cancer in comparison to matched normal breast tissue supporting its pivotal role in neoplastic signal transduction and representing a potential marker for malignant transformation.

Comparative analysis of pelvic ligaments: a biomechanics study

Introduction and hypothesisPelvic organ prolapse (POP) affects one third of women of all ages and is a major concern for gynecological surgeons. In pelvic reconstructive surgery, native ligaments are widely used as a corrective support, while their biomechanical properties are unknown. We hypothesized differences in the strength of various pelvic ligaments and therefore, aimed to evaluate and compare their biomechanical properties.Materials and methodsSamples from the left and right broad, round, and uterosacral ligaments from 13 fresh female cadavers without pelvic organ prolapse were collected. Uniaxial tension tests at a constant rate of deformation were performed and stress–strain curves were obtained.ResultsWe observed a non-linear stress–strain relationship and a hyperelastic mechanical behavior of the tissues. The uterosacral ligaments were the most rigid whether at low or high deformation, while the round ligament was more rigid than the broad ligament.ConclusionPelvic ligaments differ in their biomechanical properties and there is fairly good evidence that the uterosacral ligaments play an important role in the maintenance of pelvic support from a biomechanical point of view.

Vagina, abdominal skin, and aponeurosis: do they have similar biomechanical properties?

Introduction and hypothesisDespite minimal fundamental works, there is an increasing use of meshes in urogynecology. The concept is mainly based on experiences with abdominal wall surgery. We aimed to compare the biomechanical properties of vaginal tissue, abdominal aponeurosis, and skin.MethodsSamples from 11 fresh women cadavers without prolapse were collected. Uniaxial tension tests were performed and stress–strain curves were obtained.ResultsBiomechanical properties of the vagina, aponeurosis, and skin differed significantly. The aponeurosis was much more rigid and less extendible than the vagina and skin. Vaginal tissue was less rigid but more extendible than skin. There was no difference between the vagina and skin at low strains (p = 0.341), but a highly significant difference at large strains (p = 0.005).ConclusionsSkin and aponeurosis are not suited to predict vaginal tissue biomechanics. We should be cautious when transferring experiences from abdominal wall surgery to vaginal reconstructive surgery.

Expression of the transcriptional coregulator FHL2 in human breast cancer: a clinicopathologic study.

Objective: Although the Four and a Half LIM domain protein 2 (FHL2) has been suggested to play an important role in tumor development, this has not been investigated in breast cancer. Methods: Paraffin-embedded tissues from patients (n = 85) with primary breast cancer were submitted to immunohistochemical investigation of FHL2 expression and subsequent correlation with clinicopathologic parameters and patient survival. Results: The expression of FHL2 was confined to the cytoplasm of the tumor cells. Forty (47%) of 85 samples showed weake expression of FHL2, whereas high expression was found in 45 tumors (53%). A statistically significant positive correlation was observed between FHL2 and androgen receptor expression (P = .029). Patients with tumors expressing low amounts of FHL2 were characterized by a significantly better survival compared to those with high intratumoral FHL2 expression (P = .0215, log-rank test). The additional stratification according to adjuvant tamoxifen treatment revealed a significantly improved survival rate for patients receiving tamoxifen and being diagnosed with a tumor expressing high amounts of FHL2. This might indicate that tamoxifen is at least partially capable of reversing the negative prognostic impact of high FHL2 expression. Multivariate Cox regression analysis revealed FHL2 expression as a significant indepenent predictor of survival. Conclusion: The specific in tumor tissue points to an important functional role of FHL2 in human breast cancer. Our survival data indicate that the expression of FHL2 in primary breast cancer is a potentially relevant prognostic factor. Further studies are warranted to elucidate whether analysis of FHL2 expression is suitable to predict response to antihormonal treatment with tamoxifen.

Significance of nuclear hTra2-beta1 expression in cervical cancer

Objective. Human Tra2‐beta1, a member of the serine/arginine‐rich splicing factors, is involved in C/A‐dependent mRNA processing and regulation of gene expression. Since several genes involved in cervical carcinogenesis are alternatively spliced and contain C/A rich elements, we aimed to analyze hTra2‐beta1 expression and subcellular localization in tumor tissue of women with cervical cancer and to determine its clinical significance. Design. Retrospective study. Setting. Tertiary‐care academic medical center. Sample. One hundred and five patients with cervical cancer and a mean follow up time of 73.1 months. Methods. Immunohistochemistry of paraffin‐embedded tissues was performed and hTra2‐beta1 expression was correlated with clinico‐pathological variables including patient outcome. Results. Cytoplasmic hTra2‐beta1 protein expression was found in 20% of cases, while all tumors revealed nuclear immunoreactivity with strong expression in 54.3% of cases. There was a significant inverse correlation between nuclear and cytoplasmic protein expression, suggesting a potentially relevant shuttle process of hTra2‐beta1 between both cellular compartments. Patients with weak expressing hTra2‐beta1 tumors showed an improved survival with a tumor‐related death rate of 8.3% compared to 23.7% in patients with moderate and high intranuclear hTra2‐beta1 expression, respectively. Conclusions. Our data support the hypothesis of a biological relevance for hTra2‐beta1 expression in cervical cancer. The observed shuttle process of this splicing factor with higher concentrations in the nucleus should have pronounced effects on the cellular function and tumor biology of the affected tumors, leading to the worse patient outcome.

Surgical repair of posterior compartment prolapse : preliminary results of a novel transvaginal procedure using a four-armed polypropylene mesh with infracoccygeal and pararectal suspension

Background. Anatomical defects of the posterior vaginal compartment are a common reason for pelvic floor reconstructive surgery. The implantation of a four‐armed monofilamentous polypropylene mesh with infracoccygeal and pararectal suspension is a recently introduced innovative technique, which is believed to reduce the risk of mesh retraction and prolapse recurrences, and additionally, allows a tension‐free adjustment of the mesh. Methods. In this preliminary case series, we aimed to evaluate feasibility, intraoperative complications and short‐term follow‐up results of this novel surgical procedure in a multicentre approach. Seventy‐three patients undergoing surgery for posterior vaginal compartment prolapse were enrolled. The mean follow‐up time was 3.8 months (range: 2–6 months), and follow‐up information was available in 60/73 (82.2%) women. Results. Intraoperative complications were observed in 4.2% of cases, 2 patients with blood loss >500 ml, and one bladder injury occurring during concomitant anterior compartment surgery. Importantly, there were no intraoperative complications directly related to the implantation technique (e.g. rectum perforations), and no prolapse recurrences at follow‐up examinations 3–6 months postoperatively. Our short‐term mesh erosion rate was 3.1%. Conclusions. We conclude that this innovative procedure is a feasible and safe technique for the treatment of posterior vaginal compartment prolapse. Further prospective and multicentre trials are warranted.

Unruptured pregnancy in a non-communicating heterotopic right fallopian tube associated with left unicornuate uterus: evidence for transperitoneal sperm and oocyte migration

We report on the case of a 29-year-old patient with an unruptured pregnancy in a non-communicating heterotopic right fallopian tube. This tube was associated with a unicornuate uterus (Buttram class IIB) with a normal contralateral tube and ovary and agenesis of the right kidney. The corpus luteum of pregnancy was in the left ovary. This case provides supportive evidence for the phenomenon of transperitoneal sperm and oocyte migration.