Thickened endometrium in asymptomatic postmenopausal women - determining an optimum threshold for prediction of atypical hyperplasia and cancer

There is a lack of consensus about the significance and the management of an incidental finding of endometrial thickness (ET) > 4 mm on transvaginal ultrasound scans in postmenopausal women without postmenopausal bleeding (PMB). The data of 1995 consecutive women attending PMB clinic were collected prospectively; of them 81 (4.1%) were referred because of ET >4 mm without PMB. The prevalence of endometrial atypical hyperplasia and cancer was 4/81 (4.9%), and polyp was 20/81 (24.7%). On using a receiver operator characteristic curve, the diagnosis of endometrial atypical hyperplasia and cancer using the ET threshold of ≥10 mm had a sensitivity of 100% (95% CI = 40–100%), a specificity of 60% (95% CI = 48–71%) with AUC = 0.8 (95% CI = 0.66–0.93), p = .04. For the 35 women with an ET ≥10 mm, the prevalence of endometrial atypical hyperplasia and cancer was 4/35 (11.4%) and benign endometrial polyps was 16/35 (45.7%). The use of ≥10 mm ET threshold to prompt investigations did not miss any case of endometrial atypical hyperplasia or cancer.Impact Statement What is already known on this subject? Unlike women with PMB in whom an endometrial thickness (ET) ≤ 4 mm is considered as low risk for endometrial hyperplasia and cancer, in postmenopausal women without PMB, the threshold that separates normal from a pathologically thickened endometrium has not been standardised. A decision-analysis study in a hypothetical cohort found that ET threshold of 11 mm yields a similar separation as ≤4 mm in those with PMB. What the results of this study add? The study uses prospectively collected data from consecutive patients using a standardised format, thus minimising bias from incomplete data. This study is the third prospective series in the literature to address the dilemma of the management of asymptomatic postmenopausal women with an incidental finding of a thickened endometrium. It showed that the prevalence of endometrial atypical hyperplasia and cancer is high enough to justify investigation and for the clinical problem not to be trivialised. All cases of endometrial atypical hyperplasia and cancer had ET of ≥10 mm. What are the implications of these findings for clinical practice and/or future research? Our data strengthen the current body of literature to help the development of clinical practice guidelines about the management work-up. However, a well-designed multi-centre large prospective study is required to confirm the findings since most studies in the literature are either retrospective or small

Cellular and molecular characterisation of pelvic ligaments fibroblasts: effects of gonadal steroids

The high incidence of pelvic organ prolapse (POP) observed in postmenopausal women and in those used levormeloxifene suggested an aetiological role for the hypoestrogenic state. Further, the oestrogen-related molecular and structural changes in hip and knee ligaments, regulation of oestrogen action by extracellular matrix (ECM) proteins, and the high expression of steroid receptors in the mechanically failed connective tissue were previously reported. These observations led to the hypotheses of changed ECM composition with compensatory increase in steroid receptors expression in the prolapsed cardinal ligaments. A series of immunohistochemical studies proved the assumption that the prolapsed cardinal ligaments would have higher expression of collagen III (p=0.001), tenascin (p=0.001), oestrogen receptor α (p=0.09), androgen receptor (p=0.004), progesterone receptor (p=0.03), and lower expression of elastin (p=0.004) when compared to non-prolapsed ligaments, irrespective of menopausal status. Unpredictably, collagen I expression was directly related to the menopausal status rather than prolapse, and the prolapsed ligaments showed lower expression of oestrogen receptor β (p=0.02). HRT was assumed to rectify the prolapse-related changes in postmenopausal women, but it had only partial ameliorating effect by reducing collagen III (p=0.001) and androgen receptor (p=0.06) expression in the prolapsed ligaments to levels similar to the normal ones. Given the immunohistochemical findings, it was hypothesised that a number of genes representing the altered ECM proteins and gonadal steroids receptors would be modified. The stretch model was used assuming that the ffect of long duration mechanical stretch on primary cultures of fibroblasts derived from cardinal ligaments in vitro would be similar to the effect of chronic stretch associated with prolapse in vivo. cDNA microarray identified genes coding for regulation of actin remodelling, but it fell short of identifying alterations in gene expression commensurate with the findings of immunohistochemistry. This might be attributed to the differences between the in vivo and in vitro environment and/or the design of the stretch model used in this experiment. The cDNA microarray findings led to the hypothesis that mechanical strain e.g. in cases of increased intra-abdominal pressure and levormeloxifene could cause POP by destroying the cytoskeleton of the fibroblasts. To test this hypothesis, the effect of mechanical stretch and levormeloxifene on the morphology of the cytoskeleton of those fibroblasts grown in primary cultures was studied using fluroprobe technology. The effect of 17β-oestradiol was also investigated assuming that it would prevent and/or reverse the effect of levormeloxifene and stretch. Stretch caused major phenotypic alterations in actin morphology (p=0.0001), and levormeloxifene caused similar changes in the static fibroblasts (p=0.0001). Nonetheless, the use of oestradiol did not protect the cytoskeleton, but significantly increased cell proliferation (p=0.02), which was reduced by stretch (p=0.001), suggesting a beneficial role in the healing process. By submitting this thesis and the publication of this set of articles, it is hoped that the area of prolapse will be opened up for further objective assessment of cell-matrix interactions, and additional opportunities for creative exploration will be catalysed

Ovarian Mature Cystic Teratoma: Challenges of Surgical Management

Although ovarian mature cystic teratomas are the commonest adnexal masses occurring in premenopausal women, there are many challenges faced by gynecologists on deciding upon the best surgical management. There is uncertainty, lack of consensus, and variation in surgical practices. This paper critically analyzes various surgical approaches and techniques used to treat these cysts in an attempt to outline a unified guidance. MEDLINE and EMBASE databases were searched in January 2015 with no date limit using the key words “ovarian teratoma” and “ovarian dermoid.” The search was limited to articles in English language, humans, and female. The two authors conducted the search independently. The laparoscopic approach is generally considered to be the gold standard for the management. Oophorectomy should be the standard operation except in younger women with a single small cyst. The risk of chemical peritonitis after contents spillage is extremely rare and can certainly be overcome with thorough peritoneal lavage using warmed fluid. There is a place for surveillance in some selected cases

Cattle Uterus: A Novel Animal Laboratory Model for Advanced Hysteroscopic Surgery Training

In recent years, due to reduced training opportunities, the major shift in surgical training is towards the use of simulation and animal laboratories. Despite the merits of Virtual Reality Simulators, they are far from representing the real challenges encountered in theatres. We introduce the “Cattle Uterus Model” in the hope that it will be adopted in training courses as a low cost and easy-to-set-up tool. It adds new dimensions to the advanced hysteroscopic surgery training experience by providing tactile sensation and simulating intraoperative difficulties. It complements conventional surgical training, aiming to maximise clinical exposure and minimise patients’ harm

Cellular and molecular characterisation of pelvic ligaments fibroblasts : effects of gonadal steroids

The high incidence of pelvic organ prolapse (POP) observed in postmenopausal women and in those used levormeloxifene suggested an aetiological role for the hypoestrogenic state. Further, the oestrogen-related molecular and structural changes in hip and knee ligaments, regulation of oestrogen action by extracellular matrix (ECM) proteins, and the high expression of steroid receptors in the mechanically failed connective tissue were previously reported. These observations led to the hypotheses of changed ECM composition with compensatory increase in steroid receptors expression in the prolapsed cardinal ligaments. A series of immunohistochemical studies proved the assumption that the prolapsed cardinal ligaments would have higher expression of collagen III (p=0.001), tenascin (p=0.001), oestrogen receptor α (p=0.09), androgen receptor (p=0.004), progesterone receptor (p=0.03), and lower expression of elastin (p=0.004) when compared to non-prolapsed ligaments, irrespective of menopausal status. Unpredictably, collagen I expression was directly related to the menopausal status rather than prolapse, and the prolapsed ligaments showed lower expression of oestrogen receptor β (p=0.02). HRT was assumed to rectify the prolapse-related changes in postmenopausal women, but it had only partial ameliorating effect by reducing collagen III (p=0.001) and androgen receptor (p=0.06) expression in the prolapsed ligaments to levels similar to the normal ones. Given the immunohistochemical findings, it was hypothesised that a number of genes representing the altered ECM proteins and gonadal steroids receptors would be modified. The stretch model was used assuming that the ffect of long duration mechanical stretch on primary cultures of fibroblasts derived from cardinal ligaments in vitro would be similar to the effect of chronic stretch associated with prolapse in vivo. cDNA microarray identified genes coding for regulation of actin remodelling, but it fell short of identifying alterations in gene expression commensurate with the findings of immunohistochemistry. This might be attributed to the differences between the in vivo and in vitro environment and/or the design of the stretch model used in this experiment. The cDNA microarray findings led to the hypothesis that mechanical strain e.g. in cases of increased intra-abdominal pressure and levormeloxifene could cause POP by destroying the cytoskeleton of the fibroblasts. To test this hypothesis, the effect of mechanical stretch and levormeloxifene on the morphology of the cytoskeleton of those fibroblasts grown in primary cultures was studied using fluroprobe technology. The effect of 17β-oestradiol was also investigated assuming that it would prevent and/or reverse the effect of levormeloxifene and stretch. Stretch caused major phenotypic alterations in actin morphology (p=0.0001), and levormeloxifene caused similar changes in the static fibroblasts (p=0.0001). Nonetheless, the use of oestradiol did not protect the cytoskeleton, but significantly increased cell proliferation (p=0.02), which was reduced by stretch (p=0.001), suggesting a beneficial role in the healing process. By submitting this thesis and the publication of this set of articles, it is hoped that the area of prolapse will be opened up for further objective assessment of cell-matrix interactions, and additional opportunities for creative exploration will be catalysed.EThOS - Electronic Theses Online ServiceGBUnited Kingdo