Immunohistochemical expression pattern of metastasis suppressor KISS-1 protein in adenomyosis lesions and normal endometrium.

OBJECTIVE: Kisspeptins are multifunctional peptides; it has been shown that they act as inhibitors of tumor metastasis in a range of cancers and that they are also involved in cell invasion through regulation of matrix metalloproteinases (MMPs). The aim of this study was to investigate the expression of KISS-1 protein in adenomyosis lesions compared with matched eutopic endometrium, as well as with endometrium from patients without adenomyosis. STUDY DESIGN: In this comparative, non-interventional study, adenomyosis and corresponding eutopic endometrium samples from women with histologically proven adenomyosis after hysterectomy, and eutopic endometrium samples from women without adenomyosis were analysed. Expression of KISS-1 protein was analyzed immunohistochemically in formalin-fixed, paraffin-embedded adenomyotic tissue specimens (n=29), matched eutopic endometrium from the same patients (n=29) and normal endometrium from patients without adenomyosis (n=29). RESULTS: Using a semi-quantitative immunohistochemical score, we found that KISS-1 protein expression was higher in the adenomyotic as compared with matched eutopic glandular endometrium (p<0.05), in which in turn KISS-1 protein expression was higher than those from patients without adenomyosis (p<0.001). The inverse correlation was found in the stroma, between adenomyosis lesions and matched eutopic endometrium (p<0.01), while no statistically significant correlation was found in KISS-1 protein expression in the stroma between patients with and without adenomyosis. CONCLUSIONS: KISS-1 protein expression appears to be up-regulated in adenomyotic as compared with eutopic glandular endometrium of patients with, as well as women without adenomyosis. These findings are suggestive of the involvement of KISS-1 protein in the pathogenesis and maintenance of adenomyosis. Future studies should investigate whether KISS1 protein could be used as a marker for early and minimally invasive detection of adenomyosis, based on its differential protein expression pattern in the eutopic endometrium of patients with and without adenomyosis.

Significantly lower pregnancy rates in the presence of progesterone elevation in patients treated with GnRH antagonists and gonadotrophins: a systematic review and meta-analysis.

The current meta-analysis aimed to answer the following research question: is progesterone elevation on the day of hCG administration associated with the probability of clinical pregnancy in women undergoing ovarian stimulation for IVF using GnRH antagonists? A literature search in MEDLINE, EMBASE and CENTRAL electronic databases followed by extensive hand-searching from two independent reviewers was performed to identify relevant studies. Eventually five eligible studies (n=585 patients) were identified. No significant differences were present between patients with and those without progesterone elevation regarding female age, duration of stimulation and total dose of gonadotrophins required. However, patients with progesterone elevation were characterized by higher serum estradiol levels on the day of hCG administration (+956 pg/ml, 95% +248 to +1664, random effects model, p=0.008) and more COCs retrieved (+2.9, 95% CI +1.5 to +4.4, fixed effects model, p < 0.001). Progesterone elevation on the day of hCG administration was associated with a significantly decreased probability of clinical pregnancy per cycle (-9%, 95% CI -17 to -2, fixed model effects, p). In conclusion, in patients treated with GnRH antagonists and gonadotrophins, progesterone elevation on the day of hCG administration is significantly associated with a lower probability of clinical pregnancy.

ERBB2 (HER2) protein expression in uterine sarcomas.

PURPOSE: Multiple clinical trials in recent years have shown that breast cancer patients with primary tumors overexpressing ERBB2 can be effectively treated with specific forms of modern anti-ERBB2-targeted therapy. The aim of the present study was to analyze the expression of the ERBB2 (HER2) protein in uterine sarcomas, in order to investigate the possibility of applying this treatment modality in uterine sarcomas. METHODS: The expression of ERBB2 has been analyzed immunohistochemically in formalin-fixed paraffin-embedded primary uterine sarcomas (n = 11). RESULTS: Using a semi-quantitative immunohistochemical score, we found that ERBB2 expression was very weak in the majority of tumors, with only three sarcomas showing moderate ERBB2 expression. Published studies evaluating the same issue in small numbers of uterine sarcomas reached similar findings. CONCLUSION: Overall, ERBB2 expression appears to be weak in uterine sarcomas. However, targeted treatment might still be feasible in a subgroup of patients with uterine sarcomas overexpressing ERBB2.

Virilizing ovarian hilus (Leydig) cell tumor with concurrent contralateral hilus cell hyperplasia: a rare diagnosis.

Ovarian hilus or Leydig cell tumor and ovarian hilus cell hyperplasia are rare clinical entities, causing virilization in both pre- and postmenopausal women. Differentiation between these two conditions is not always straightforward; the former is usually unilateral appearing as a single, grossly visible, circumscribed mass of hilus cells, while the latter is usually bilateral, appearing as diffuse microscopic aggregates of hilus cells. We report herein an extremely rare case of ovarian hilus or Leydig cell tumor, presenting concurrently with contralateral ovarian hilus cell hyperplasia in a postmenopausal woman with virilization. To the best of our knowledge, only four such cases have been previously reported in the literature. Ovarian hilus cell tumors and hilus hyperplasia almost always have benign biological behavior, thus making bilateral salpingo-oophorectomy an appropriate and sufficient therapeutic approach.

Mucocele of the appendix mimicking an adnexal mass: a case report.

Mucocele of the appendix is a rare entity usually mimicking an adnexal tumour. There is no specific imaging or screening method to determine the diagnosis with certainty preoperatively. Appendiceal malignancy can be the underlying cause, although it is not common. We present a case of an appendiceal mucocele mimicking an ovarian tumour by both clinical and imaging (TVS and MRI) methods. This pathological condition should be considered by all the gynaecologists in the differential diagnosis of a right-sided pelvic mass.

Steroid receptor expression in human endometrium during the follicular phase of stimulated cycles.

BACKGROUND: No data are currently available regarding kinetics of human endometrial steroid receptors in stimulated cycles. METHODS: In 31 patients (age <39 years) stimulated with gonadotrophins and GnRH antagonists for intrauterine insemination (IUI) an endometrial biopsy was performed on the first day after the end of menstruation and a second biopsy was performed two (Group 0 + 2, n = 10) or four (Group 0 + 4, n = 11) days after the first biopsy, or on the day of hCG administration (Group 0 + hCG, n = 10). Expression of progesterone (PR) and estrogen (ER) receptor was investigated by immunohistochemistry using monoclonal antibodies. RESULTS: PR and ER levels were significantly increased in the second versus the first biopsy, in all groups analyzed (P = 0.01), in both stromal and glandular cells. Between the three groups compared, a significant increase in PR expression was observed for glandular cells (P = 0.03), with the highest value observed in Group 0 + 4. Moreover, the increase in PR expression in stromal cells differed between groups (P = 0.01), with the highest value observed in the Group 0 + hCG. CONCLUSIONS: In stimulated cycles for IUI, ER expression in both glandular and stromal endometrial cells, after an initial increase, does not appear to change significantly during the follicular phase. On the contrary, during the same period of time, following an initial rise, PR expression in glandular and stromal cells continues to increase.

A unique case of palatinate tonsil metastasis from endometrial cancer.

Metastases from malignancies of the female genital tract to the tonsils have never been reported. A case of a 55-year-old woman presenting with a palatinate tonsil tumour two and half years after primary diagnosis of endometrioid endometrial adenocarcinoma (FIGO Stage IB, G2) and six months after local disease recurrence is presented. The tonsillar malignancy was poorly differentiated and tumour cells were immunohistochemically positive to LMW keratin and EMA, and negative to HMW keratin and LCA, strongly suggesting a possible endometrial origin of the tumour. Metastatic disease was treated with systemic chemotherapy, but the patient soon succumbed due to rapid disease progression. In conclusion, a unique case of a palatinate tonsil tumour as the first metastatic site in an endometrial cancer patient is reported.

A rare case of renal cell carcinoma metastasizing to the uterine cervix.

Metastatic tumors to the uterine cervix originating from malignancies in other organs are very rare. A case of a 45-year-old white woman presenting with vaginal bleeding, due to renal cell carcinoma metastasizing to the cervix, is reported. The patient had been treated four years and five months earlier due to two primary malignancies: colon adenocarcinoma and renal cell carcinoma. After D&C, microscopic examination and immunohistochemical staining showed that the tumor was metastatic, originating from the renal cell carcinoma. Radical hysterectomy with bilateral salpingo-oophorectomy and pelvic lymph node resection followed, and postoperatively the patient received targeted therapy with sutinib malate. The possibility of metastasis from another primary should be considered in the differential diagnosis of tumors of the uterine cervix in order to plan optimal management.

Human placental lactogen and color Doppler in predicting expulsion of retained adherent placenta: a new clinical observation.

PURPOSE: To present a new clinical observation made in three cases of retained adherent placenta, a rare obstetrical complication, associated with potentially life-threatening hemorrhage. METHODS: Three consecutive cases of retained adherent placenta are presented. RESULTS: Diagnosis of placenta increta in two and placenta percreta in one case was established with ultrasound and MRI. Methotrexate 50 mg i.v. (300 mg total dose) and follinic acid 0.1 mg/kg were administered on alternating days, over 12 days. On follow-up, placental perfusion on color Doppler was present up to the point when circulating hPL levels were no longer detectable; this was followed in all cases by spontaneous placental expulsion within 10 days. CONCLUSIONS: The observation that both color Doppler and human placental lactogen can be used to monitor response to therapy and predict placental expulsion should be evaluated in future cases of retained adherent placenta.

Hormone therapy for postmenopausal breast cancer survivors: a survey among obstetrician-gynaecologists.

PURPOSE OF INVESTIGATION: To investigate the attitude of Greek obstetrician-gynaecologists towards prescription of hormone therapy to postmenopausal breast cancer survivors. METHODS: An anonymous questionnaire was sent to members of the Hellenic Society of Obstetrics and Gynaecology with a hypothetical case and a series of relevant questions. RESULTS: Three hundred valid answers were received. Hormone therapy would be prescribed to a breast cancer survivor by only 8%; 80% of these would prefer tibolone. In contrast, 92% would not prescribe hormone therapy; 97% would do so due to the risk of disease recurrence; 70% would not prescribe any alternative therapy, 21% would prescribe CNS-active compounds and 7% SERMs. CONCLUSIONS: The vast majority of Greek obstetrician-gynaecologists would not prescribe hormone therapy for menopausal symptoms in breast cancer survivors due to the theoretical risk of disease recurrence. Among those who would not prescribe hormone therapy, 21% would opt to CNS-active compounds.

Apert syndrome: the current role of prenatal ultrasound and genetic analysis in diagnosis and counselling.

Apert syndrome is a rare congenital malformation syndrome characterized by the triad of cutaneous and progressive bony syndactyly, midfacial hypoplasia and craniosynostosis. Two missense mutations of the gene encoding the fibroblast growth factor receptor 2 (FGFR2) have been implicated in most cases. We report a case of Apert syndrome detected on prenatal ultrasound. Postnatal genetic analysis showed, for the first time, that the previously reported P253R mutation of the FGFR2 gene is also prevalent in southeast Europe. After prenatal sonographic detection of anomalies suggestive of Apert syndrome, parents should be counselled about prognosis and risk of recurrence, and the option of amniocentesis should be offered.

KIT protein expression in uterine sarcomas: an immunohistochemical study and review of the literature.

PURPOSE: The aim of the present study was to investigate the possibility of treating uterine sarcomas with imatinib mesylate. Imatinib mesylate, a selective tyrosine kinase inhibitor, is very efficient against mesenchymal tumors of the gastrointestinal tract, known as GISTs. Imatinib mesylate acts against a tyrosine kinase encoded by the KIT gene in GISTs, and is more effective in tumors expressing this protein. METHODS: Expression of KIT was analyzed immunohistochemically (n = 12) in formalin-fixed paraffin-embedded primary uterine sarcomas. RESULTS: Using a semi-quantitative immunohistochemical score we found that KIT expression was very weak in the majority of tumors, while none of the uterine sarcomas tested showed strong expression. Overall, published studies addressing this issue in small series of uterine sarcomas yielded similar results. CONCLUSION: Current data suggest that it is unlikely that imatinib mesylate could be used effectively as a single agent in patients with uterine sarcomas.

Vaginal wall fibroid.

Localization of leiomyomas in the vaginal wall is very rare. We report about a case of a vaginal leiomyoma in the anterior vaginal wall, preoperatively identified with sonography and CT. Surgical enucleation was performed. Surgical removal in these cases is safe and usually with minimal bleeding.

Fetal abdominal subcutaneous tissue thickness measured by ultrasound at term is associated with birth weight and mode of delivery.

PURPOSE: To determine if measurement of fetal abdominal subcutaneous tissue thickness (FASTT) at term can predict birth weight, mode of delivery and perinatal outcome. METHODS: A prospective study with 352 normal, singleton pregnancies in the vertex presentation examined with real-time ultrasound at 37-39 weeks' gestation. RESULTS: FASTT was positively correlated with birth weight (Pearson's, r = 0.784, p < 0.001). Fetuses with low FASTT were more likely to be delivered through normal vaginal delivery (7.8 +/- 0.1 mm), while higher FASTT was correlated with operative vaginal delivery (7.9 +/- 0.2 mm) and cesarean section (8.6 +/- 0.3 mm) (ANOVA, p = 0.034). In contrast, FASTT was not correlated with intrapartum CTG, labor duration and Apgar scores. CONCLUSIONS: In normal pregnancies, FASTT at term is positively associated with birth weight. With increasing FASTT the likelihood of operative vaginal and cesarean delivery increases. FASTT is not associated with perinatal outcome.

The role of hysteroscopy in the current management of the cervical polyps.

The current management of patients with cervical polyps may include different approaches and protocols, such as a simply removal of the polyp in most cases at an office setting, surgical dilatation and curettage, electrosurgical excision or hysteroscopic polypectomy. Exploration of the cervical canal and uterine cavity by hysteroscopy determines the exact origin of the polyp pedicle (cervical or endometrial) and if there is any concurrent endometrial pathology. The majority of cervical polyps are asymptomatic, and their incidence is increasing with age. Symptomatic cervical polyps may cause intermenstrual bleeding, postcoital bleeding, heavy menses, postmenopausal bleeding and vaginal discharge. Cervical polyps may be detected by routine gynaecological examination, colposcopy, filling defects on hysterosalpingogram, gynaecological ultrasound (abdominal, transvaginal or sonohysterography) or endometrial biopsy. The location, number, and size of cervical polyps are best determined with diagnostic hysteroscopy. In the past, simple twisting or avulsion of the polyp or blind curettage was the standard surgical treatment of choice. However, this treatment often leaves residual polyp fragments in the cervical canal. Difficulty may also occur in differentiating endocervical from endometrial lesions. In addition, up to 25% of patients who have cervical polyp, have also a coexisting endometrial polyp, so there is a need for evaluation of the endometrial cavity. It is important to note the usefulness of hysteroscopy to manage a patient with a cervical polyp, especially when she presents abnormal uterine bleeding, in order to make an accurate diagnosis and offer appropriate treatment.

Among patients treated with FSH and GnRH analogues for in vitro fertilization, is the addition of recombinant LH associated with the probability of live birth? A systematic review and meta-analysis.

The aim of this systematic review and meta-analysis was to assess whether the addition of recombinant luteinizing hormone (LH) increases live birth rate, among patients treated with follicle stimulating hormone (FSH) and gonadotrophin-releasing hormone (GnRH) analogues for in vitro fertilization (IVF). Eligible studies were randomized controlled trials (RCTs) answering the research question that contained sufficient information to allow ascertainment of whether randomization was true and whether equality was present between the groups compared, regarding baseline demographic characteristics, gonadotrophin stimulation protocol, number of embryos transferred and luteal phase support administered. A literature search identified seven RCTs (701 patients) that provided the information of interest, among which five reported agonist and two antagonist cycles. The reported outcome measure, clinical pregnancy, was converted to live birth using published data in one study. No significant difference in the probability of live birth was present with or without rLH addition to FSH (odds ratio [OR]: 0.92, 95% confidence interval (CI): 0.65-1.31; P = 0.65). This finding remained stable in subgroup analyses that ordered the studies by dose of rLH added, the type of analogue used to inhibit premature LH surge, the time rLH was added during the follicular phase, the age of patients analysed, the presence of allocation concealment and by the way the information on live birth was retrieved. In conclusion, the available evidence does not support the hypothesis that the addition of recombinant LH increases the live birth rate in patients treated with FSH and GnRH analogues for IVF.

Is progesterone elevation on the day of human chorionic gonadotrophin administration associated with the probability of pregnancy in in vitro fertilization? A systematic review and meta-analysis.

The role of progesterone elevation on in vitro fertilization (IVF) outcome has remained a debatable issue for several years. The aim of this systematic review and meta-analysis was to evaluate whether progesterone elevation on the day of human chorionic gonadotrophin (hCG) administration is associated with the probability of pregnancy. Eligible studies were considered those in which patients did not participate more than once. A literature search in MEDLINE, EMBASE and CENTRAL identified 12 eligible studies, 10 of which were retrospective. The majority (n = 10) of these studies did not detect a statistically significant association between progesterone elevation and the probability of pregnancy. Meta-analysis was performed only for the studies (n = 5) that provided data on clinical pregnancy per patient reaching hCG administration for final oocyte maturation. No statistically significant association between progesterone elevation and the probability of clinical pregnancy was detected (Odds ratio: 0.75, 95% confidence interval 0.53-1.06; P = 0.10). This finding persisted in the sensitivity analyses performed, which excluded the studies that did not report clearly that measurement of progesterone did not affect patients' management and those that did not report definition of clinical pregnancy. In addition, subgroup analyses were conducted on the basis of type of gonadotrophin-releasing hormone GnRH analogue used and on the value of serum threshold used to classify patients in those with or without progesterone elevation. These analyses, however, did not materially change the results obtained. In conclusion, the best available evidence does not support an association between progesterone elevation on the day of hCG administration and the probability of clinical pregnancy in women undergoing ovarian stimulation with GnRH analogues and gonadotrophins for IVF.

Results after hysteroscopic management of premenopausal patients with dysfunctional uterine bleeding or intrauterine lesions.

AIM: The purpose of this study was to evaluate the efficacy, safety and benefits of hysteroscopic surgery in the management of dysfunctional uterine bleeding or intrauterine lesions causing menstrual disorders in premenopausal women. METHODS: We enrolled in this study 228 patients who underwent operative hysteroscopy because of metrorrhagia due to endometrial polyps or submucous myomas diagnosed by hysterosalpingography, transvaginal ultrasound and diagnostic hysteroscopy. In addition, the study population included 27 patients who presented dysfunctional uterine bleeding resistant to medical therapy. These patients underwent total or partial transcervical resection of endometrium (TCRE). RESULTS: Operative hysteroscopy was a successful procedure in 250 of the 255 cases (98%) but it needed to be repeated in three cases with large submucous myomas of type I and II and after two polypectomies. Mean duration of the procedure was 26.1 min (range 4-58) and mean postoperative hospital stay was six hours (range 2-48 hours). There were two cases with fluid overload and five with postoperative uterine bleeding reported in this study. During postoperative follow-up (12-36 months) the majority of patients (246/255 or 96.5%) were free of symptoms. After total or partial TCRE, 23/27 patients (85.2%) reported eumenorrhea or hypomenorrhea, 2/27 (7.4%) amenorrhea and 2/27 (7.4%) metrorrhagia (due to adenomyosis). CONCLUSION: Hysteroscopic surgery is an effective and safe method for the management of benign intracavitary pathology or the treatment of dysfunctional uterine bleeding. In addition, it has the advantages of quick recovery, early return to normal activities and reduced hospital stay for the patient. Careful monitoring of the patients avoids serious complications.