Mutational and Immunophenotypic Profiling of a Series of 8 Tubo-ovarian Carcinosarcomas Revealed a Monoclonal Origin of the Disease.

Carcinosarcomas are rare, highly aggressive neoplasms composed of a combination of carcinomatous and sarcomatous elements. These tumors represent a paradigmatic field for the study of intratumor heterogeneity. A series of 8 tubo-ovarian carcinosarcomas was characterized for the following: (i) immunohistochemical expression of MNF116, epithelial membrane antigen, vimentin, S100, chromogranin, synaptophysin, desmin, myogenin (MYF4), and p53; (ii) mutational profiling of KRAS, BRAF, PIK3CA, NRAS, TP53, and DICER1 genes. Heterologous differentiation was present in 6 of 8 tumors. Cytokeratin MNF116 and epithelial membrane antigen were positive in all the carcinomatous components and in 87.5% and 50.0% of the sarcomatous components, respectively. The sarcomatous components showed positive staining for vimentin in all cases. Two cases demonstrated positivity for neuroendocrine markers in their carcinomatous components. All rhabdomyosarcomas were positive for desmin and MYF-4. Chondrosarcomas were positive for S100. All but one tumor showed similar p53 immunoreactivity in both the carcinomatous and sarcomatous components, and one case showed cytoplasmic p53 expression. Three of 8 cases (37.5%) showed TP53 mutations, and, in 2 cases, the TP53 mutation was shared by both epithelial and mesenchymal components. DICER1 mutation was found in all components of one case. Mutations in KRAS, NRAS, BRAF, and PIK3CA genes were not found in the study cohort. Our results highlight the heterogeneity of ovarian carcinosarcomas at the phenotypic level. A common mutational signature was observed in both components in 3 of 4 informative tumors. More studies are required to dissect different levels of ovarian carcinosarcomas' heterogeneity in order to define the best therapeutic approaches to these aggressive neoplasms.

Apheresis and intravenous immunoglobulins used in addition to conventional therapy to treat high-risk pregnant antiphospholipid antibody syndrome patients. A prospective study.

Pregnant women with triple antibody positive antiphospholipid syndrome (APS) who have had thrombosis or a history of early, severe pregnancy complications are generally considered at high risk of pregnancy loss. The objectives of this study were to investigate the efficacy and safety of a relatively new treatment protocol used in addition to conventional therapy in high-risk pregnant patients affected with primary APS. The study's two inclusion criteria were: (1) the presence of triple antiphospholipid positivity, (2) previous thrombosis and/or a history of one or more early, severe pregnancy complications. Eighteen pregnancies occurring between 2002 and 2015 in 14 APS patients, (mean age 34.8±3.6 SD) were monitored. All 14 (100%) patients had triple antiphospholipid positivity. In addition, six of them (42.8%) had a history of thrombosis, four (28.6%) had one or more previous early and severe pregnancy complications, and four (30.8%) met both clinical study criteria. The study protocol included weekly plasmapheresis or immunoadsorption and fortnightly 1g/kg intravenous immunoglobulins. Seventeen of the pregnancies (94.4%) produced live neonates, all born between the 26th and 37th weeks of gestation (mean 33.1±3.5 SD). One female (5.5%), born prematurely at 24 weeks, died of sepsis a week after birth. There were two cases (11.1%) of severe pregnancy complications. No treatment side effects were registered. Given the high live birth rate and the safety associated to it, the study protocol described here could be taken into consideration by medical teams treating high-risk APS pregnant patients.

Menstrual cycle length: a surrogate measure of reproductive health capable of improving the accuracy of biochemical/sonographical ovarian reserve test in estimating the reproductive chances of women referred to ART.

BACKGROUND: Aim of the study was to investigate whether menstrual cycle length may be considered as a surrogate measure of reproductive health, improving the accuracy of biochemical/sonographical ovarian reserve test in estimating the reproductive chances of women referred to ART. METHODS: A retrospective-observational-study in Padua' public tertiary level Centre was conducted. A total of 455 normo-ovulatory infertile women scheduled for their first fresh non-donor IVF/ICSI treatment. The mean menstrual cycle length (MCL) during the preceding 6 months was calculated by physicians on the basis of information contained in our electronic database (first day of menstrual cycle collected every month by telephonic communication by single patients). We evaluated the relations between MCL, ovarian response to stimulation protocol, oocytes fertilization ratio, ovarian sensitivity index (OSI) and pregnancy rate in different cohorts of patients according to the class of age and the estimated ovarian reserve. RESULTS: In women younger than 35 years, MCL over 31 days may be associated with an increased risk of OHSS and with a good OSI. In women older than 35 years, and particularly than 40 years, MCL shortening may be considered as a marker of ovarian aging and may be associated with poor ovarian response, low OSI and reduced fertilization rate. When AMH serum value is lower than 1.1 ng/ml in patients older than 40 years, MCL may help Clinicians discriminate real from expected poor responders. Considering the pool of normoresponders, MCL was not correlated with pregnancy rate while a positive association was found with patients' age. CONCLUSIONS: MCL diary is more predictive than chronological age in estimating ovarian biological age and response to COH and it is more predictive than AMH in discriminating expected from real poor responders. In women older than 35 years MCL shortening may be considered as a marker of ovarian aging while chronological age remains most accurate parameter in predicting pregnancy.

Is it time to shift the attention on early stages embryo development to avoid inconclusive evidence on HPV-related infertility: debate and proposal.

BACKGROUND: Current evidence about in-vivo effects of HPV cannot definitively clarify the possible negative role of this worldwide common infection in early embryo development. However in-vitro evidence, seems to underline a possible negative effect of HPV in increasing blastocyst apoptosis and in reducing the endometrial implantation of trophoblastic cells. On these bases we believe that a new scientific approach is necessary to better understand the real role of male and female HPV infection in infertility and early pregnancy development. METHODS: English literature review of manuscripts focused on HPV infection and human reproduction was conducted. We performed a critical analysis of evidence and possible bias affecting both in-vivo and in-vitro studies regarding this topic. RESULTS: The biggest limitation of the in-vivo studies is due to the inappropriate timing of HPV effects evaluation since evidence about in-vitro studies strongly suggests that a large part of HPV negative effects occurs during a very early stage of embryo development. All the efforts of the scientific community to investigate the real role of HPV in human reproduction disorders cannot underestimate the severe BIAS of actual evidence in postulating new hypothesis and research projects which are fundamental to clarify if HPV may be associated with unexplained couples infertility and early miscarriages. CONCLUSIONS: If the relationship between HPV gametes infection and early human reproduction step impairment will be confirmed, the HPV male and couple vaccination may represent a reliable option to improve fertility in some couples affected by infertility actually classified as "idiopathic" but maybe linked to HPV infection.

Extragenital Müllerian adenosarcoma with pouch of Douglas location.

BACKGROUND: Of all female genital tract tumors, 1-3% are stromal malignancies. In 8-10% of cases, these are represented by Müllerian adenosarcoma an extremely rare tumor characterized by a stromal component of usually low-grade malignancy and by a benign glandular epithelial component. Variant that arises in the pouch of Douglas is scarcely mentioned in the medical literature. CASE PRESENTATION: A 49-year-old para-0 woman, was seen at our OB/GYN-UNIT because she complained vaguely of pelvic pain. She had a mass of undefined nature in the pouch of Douglas. A simple excision of the mass showed low-grade Müllerian adenosarcoma with areas of stromal overgrowth. One and a half year after surgery, at another hospital, a mass was detected in the patient's posterior vaginal fornix and removed surgically. Six months later she came back to our observation with vaginal bleeding and mass in the vaginal fornix. We performed radical surgery. The pathological examination showed recurrent adenosarcoma. Surgical treatment was supplemented by radiation therapy. CONCLUSIONS: The case of Müllerian adenosarcoma reported here is the third known so far in the literature that was located in the pouch of Douglas. To date, only two other such cases have been reported, including one resulting from neoplastic degeneration of an endometriotic cyst.

Randomised prospective study of abdominal wall closure in patients with gynaecological cancer.

BACKGROUND: Median laparotomy is the most common approach to the abdominopelvic cavity in patients with gynaecological tumours. AIMS: The primary endpoint of the study was to evaluate the onset of incisional hernia. The secondary endpoint was to evaluate the onset of infection, wound dehiscence, wound infection, and scar pain during the post-operative period. METHODS: A total of 191 patients were eligible for the study. They were divided into three groups. Group A underwent en bloc closure of the peritoneum and fascia with Premilene suture, Group B en bloc closure of the peritoneum and fascia with Polydioxanone suture, and Group C separate closure of the peritoneum and fascia with single stitches of Ethibond suture. Statistical analysis was performed using the Statistical Software Package for Social Sciences 12.0. RESULTS: Group A and Group B comprised 63 patients, and Group C included 65 patients. The three groups proved homogeneous on statistical analysis (P > 0.05). The statistical analysis did not reveal significant differences between the different suture types and techniques with respect to the incidence of incisional hernia (P > 0.05). CONCLUSION: In our study, the incidence of incisional hernia was 8%. Randomised patients were homogeneous for sample size and risk factors. No significant differences were found between suture types or techniques. Currently, there is no suture material or technique that can be considered superior to others. When possible, we believe that the best way to prevent incisional hernia is to preserve the integrity of the abdominal wall using minimally invasive techniques.

Two case reports of bowel leiomyomas and review of literature.

We report two cases of two women underwent laparoscopic hysterectomy and myomectomy. During surgery, three myomas were identified as completely detached from the uterus, and attached to the bowel. Patients's history revealed a laparoscopic myomectomy. Our first hypothesis therefore was that these were lost myomas of the first surgery. However, only one leyomyoma was removed in both patients. Therefore, we can assume that these myomas were not certainly not lost-myomas and we may conclude that it could be either as residues of previous morcellation or they were pedunculated-myomas that have been spontaneously detached from the uterus and re-implanted onto the bowel.

Transvaginal ultrasound and sonohysterography for assessment of postpartum residual trophoblastic tissue.

OBJECTIVE: To compare the accuracy of transvaginal ultrasound and sonohysterography (SHG) in diagnosing residual trophoblastic tissue in postpartum women and to assess the adverse effects and complications of the SHG procedure. METHODS: A prospective study of patients with postpartum bleeding enrolled for clinical symptoms and signs of residual trophoblastic tissue. All women underwent transvaginal ultrasound and SHG. Uterine cavity curettage was performed in all women and the material collected was sent for pathologic examination. RESULTS: Among 84 patients, transvaginal ultrasound revealed residual trophoblastic tissue in 60 women, whereas SHG detected residual trophoblastic tissue in 48 and blood clots in 12. Pathologic examination confirmed trophoblastic tissue in 48 patients and blood clots in 12. Fifteen (17.9%) patients experienced adverse effects after SHG. Thirteen (15.5%) experienced postprocedural fever that resolved with antibiotics. Two women (2.4%) had severe complications of infection: 1 required surgery for peritonitis, which revealed salpingitis and a pelvic abscess; 1 experienced fever and mild abdominal pain that resolved with antibiotics after 10 days of hospitalization. CONCLUSIONS: Although SHG showed greater accuracy than transvaginal ultrasound in detecting residual trophoblastic tissue, a high proportion of patients experienced adverse effects.

Uterine tumors resembling ovarian sex cord tumors: a case report of conservative management in young women.

Uterine tumors resembling ovarian sex cord tumors (UTROSCT) are distinguished into two separate groups: endometrial stromal tumors with sex cord-like elements (Group I), which have an unfavorable prognosis; and UTROSCT proper (group II), with more than 40% sex cord-like differentiation and less endometrial component, which are biologically less aggressive than the tumors of the other group. We report the case of a young woman with UTROSCT treated by minimally invasive hysteroscopic surgery. This is one of the few cases reported in the literature that have been managed conservatively.

Diagnostic accuracy of IOTA ultrasound morphology in the hands of less experienced sonographers.

AIM: The purpose of our study was to evaluate the ability of the International Ovarian Tumor Analysis (IOTA) classification and its impact on the identification of benign and malignant adnexal masses by less experienced sonographers. METHODS: One hundred and five patients undergoing elective surgical treatment for single adnexal masses at the University of Parma were enrolled. After the final diagnosis, we had the ultrasound recordings reviewed retrospectively by a group of three residents, and the features of each adnexal mass were evaluated according to the morphological score reported by the IOTA Group. RESULTS: Based solely on the qualitative classification of the IOTA Group unilocular cysts were associated with a high, significant probability of a benign lesion (odds ratio (OR) = 12.6 (95% CI, 1.61-99.10), P < 0.001). This probability remained high also with multilocular cysts (OR = 7.9 (95% CI, 1.00-62.38), P < 0.05). By contrast, multilocular-solid cysts were significantly associated with the probability of malignancy (OR = 6.4 (95% CI, 1.81-22.70), P < 0.001), as were solid masses (OR = 5.5 (95% CI, 1.48-20.92), P < 0.05). None of the five ultrasound categories of lesions could be significantly correlated with borderline masses. CONCLUSIONS: A simple qualitative classification based solely on the recognition of five different ultrasound categories may be enough to guide the physician to an accurate identification of the nature of the mass. Our findings confirm the diagnostic reliability of the IOTA Group classification by less experienced sonographers. This system is especially helpful because it is capable of discriminating between ovarian masses without further tests and clinical examinations.

Gender differences in endothelial progenitor cells and cardiovascular risk profile: the role of female estrogens.

OBJECTIVE: Endothelial progenitor cells (EPCs) participate in vascular homeostasis and angiogenesis. The aim of the present study was to explore EPC number and function in relation to cardiovascular risk, gender, and reproductive state. METHODS AND RESULTS: As measured by flow-cytometry in 210 healthy subjects, CD34(+)KDR(+) EPCs were higher in fertile women than in men, but were not different between postmenopausal women and age-matched men. These gender gradients mirrored differences in cardiovascular profile, carotid intima-media thickness, and brachial artery flow-mediated dilation. Moreover, EPCs and soluble c-kit ligand varied in phase with menstrual cycle in ovulatory women, suggesting cyclic bone marrow mobilization. Experimentally, hysterectomy in rats was followed by an increase in circulating EPCs. EPCs cultured from female healthy donors were more clonogenic and adherent than male EPCs. Treatment with 17beta-estradiol stimulated EPC proliferation and adhesion, via estrogen receptors. Finally, we show that the proangiogenic potential of female EPCs was higher than that of male EPCs in vivo. CONCLUSIONS: EPCs are mobilized cyclically in fertile women, likely to provide a pool of cells for endometrial homeostasis. The resulting higher EPC levels in women than in men reflect the cardiovascular profile and could represent one mechanism of protection in the fertile female population.