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Introduction The serum levels of glycoprotein human epididymis protein 4 (HE4) have been widely investigated in patients with ovarian cancer as a tumor marker to differentiate benign gynecological tumors from ovarian cancers (OC). A few studies demonstrated the promising role of HE4 in endometrial cancer (EC) too. The aim of this review is to provide an outline of published studies investigating HE4 in the diagnosis of gynecologic malignancies, focusing on its role in OC and EC. Evidence acquisition We conducted a systematic review of literature from January 1952 to June 2018 on the role of HE4 in OC and EC focusing on the diagnostic power in terms of sensitivity and specificity. Evidence synthesis We identified 49 articles with an overall sample size of 12,631 patients in OC group and five studies with an overall sample size of 1221 patients in EC group. We stated that HE4 had a pooled sensitivity of 78% and specificity of 86% in the detection of borderline or malignant OC and a pooled sensitivity of 78.8% and specificity of 100% in EC diagnosis. Conclusions This systematic review confirms the importance of HE4 in the diagnosis of epithelial ovarian cancer and its promising role in endometrial cancer (endometrioid histology).

Introduction Cancer during pregnancy is a rare but challenging condition. More women delay childbearing and consequently the incidence of cancer during pregnancy is constantly increasing. Evidence acquisition An extensive electronic search was performed in PubMed and Scopus. Only studies written after 1985 were considered eligible for this review. Abstracts, conference papers, book chapters, animal studies, commentaries as well as editorials articles were excluded from this review. Evidence synthesis Cancer treatment during pregnancy is possible, but both maternal and fetal conditions need to be preserved. Randomized clinical trials are not feasible and current evidence are mainly based on case-series, small case reports and expert opinion. Cervical and ovarian cancers are the most common gynecological cancers diagnosed during pregnancy. Surgery and chemotherapy after the first trimester seem to be relatively safe for the newborn. Platinum-based chemotherapy administered during the 2nd-3rd trimester showed comparable adverse effects in newborns to those in the general population. Babies exposed to antenatal chemotherapy might be more likely to develop small for gestational age and NICU admission, than babies not exposed. Conclusions Management of pregnant women with cancer should be performed in specialized cancer centers and all cases should be discussed with a multidisciplinary approach. In the present review, we discuss the current recommendations for the management of pregnancies complicated by cancer and neonatal outcomes.

TFeasibility and favorable short term outcome with respect to complications has been already convincingly shown for robotic-assisted radical hysterectomy. With respect to oncological safety there are at present only few studies mainly retrospectively. However, these seem to confirm the data from classical laparoscopic surgery that oncological outcome is not impaired by minimal-invasive surgery. Since robotic-assisted radical hysterectomy is in fact technically supported laparoscopic radical hysterectomy it is reasonable to assume that results are at least equal compared to the classical laparoscopic approach.

Endometriosis is the presence of endometriotic tissue outside of the uterus, composed of endometriotic glands and stroma. It affects between 10% to 12% of women in reproductive age. It presents with dysmenorrhea, dyspareunia, chronic pelvic pain, infertility, urinary or digestive symptoms. Diagnosis is based on clinical suspicion, clinical exam, pelvic ultrasound or pelvic magnetic resonance, and confirmed by laparoscopy with pathology studies. Its management is better understood nowadays. However, its association with neoplasia has been questioned for many years. It probably plays a role in the etiology of gynecological cancers, mainly ovarian neoplasia. In our review, we separately compared endometriosis and endometrioma to cancer, in terms of mutual causality, common risk factors, distinction based on histological findings, in addition to molecular and genetic pathways behind this association. This article reviews the English literature for studies on the association between endometriosis and gynecological cancers. Additional reports were collected by systematically reviewing all references from retrieved papers.

Proteomics has recently emerged as a powerful approach both for discovering biomarkers as well as for understanding the physiopathology of unclear gynecological-obstetrical disorders. Currently, several biological fluids and fetal tissues were successfully tested, including maternal plasma, amniotic fluid, cervical-vaginal fluid, urine, saliva, placental trophoblast, amnio-chorionic membranes and cord blood. The potential of proteomics on the polycystic ovary syndrome (PCOS) involves biomarkers discovery for a more accurate diagnosis of the syndrome and identification, within the patients with PCOS, those who respond more easily to treatment and those who will be at increased risk for future metabolic complications. The proteomic approach applied to patients with endometriosis would allow not only a non-invasive early diagnosis, but also a staging of the disease and a prediction of infertility risk. Proteomics also involves oncological field, in order to discover biomarkers that allow early diagnosis and prognosis of female genital malignancies. In addition to this, proteomics could be used to understand and predict obstetrical complications such as recurrent spontaneous abortion, preterm birth and preeclampsia. However, further studies are needed on a larger cohort of patients to introduce these biomarkers in clinical practice.

Advances in imaging techniques over the past few decades have continued at an astounding pace and now physicians have various modalities to examine the human body. These imaging techniques may be used to assist in diagnosis, staging, and follow-up of oncology patients. The increasing complexity of diagnostic radiology provides a challenge to radiologists and oncologists to use these tools in a clinically efficient and cost-effective manner. The ultimate goal is to offer a safe and effective examination that provides clinically relevant information for the management of an individual patient. Currently ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) are being used to evaluate patients with gynecological malignancies. Goal of this review is to provide an overview of clinically available imaging techniques and discuss relative strengths and weaknesses. This article summarizes the diagnostic performance (sensitivity, specificity, positive and negative likelihood ratios) of US, CT, MRI and PET/CT in the diagnosis of various gynecological diseases and tumors. US is the first-line imaging modality of choice and is used to discriminate between benign and malignant adnexal masses and for characterizing adnexal tumors such as dermoid cyst, endometrioma, hemorrhagic corpus luteum, etc., for diagnosing intrauterine pathology in women with dysfunctional uterine bleeding, and for confirming or refuting pelvic pathology in women with pelvic pain. MRI can play a role in detecting the extent of disease and helps in local staging of gynecologic tumors. CT can be used to detect extrapelvic disease and PET/CT can assist in detecting distant metastatic disease in order to select appropriate surgical candidates.

The aims of this study were to verify the predictive performance of color-Doppler analysis in the differential diagnosis of adnexal masses and to evaluate the prognostic value of a new "vascular score".One-hundred-ninety-six patients referred to our Institute for adnexal masses were evaluated with color and pulsed Doppler within 2-3 days from surgery, and the velocimetric results were compared to histopathological data. On the basis of histopathology, patients were classified in 166 with benign and 30 with malignant ovarian tumors.The predictivity obtained with color Doppler analysis ("vascular score") was compared to that of some "morphological scores" commonly used in the literature. The sensitivity was 100% for all the techniques used, but Doppler analysis had a higher specificity with respect to the others (95% vs max 76% for echographic techniques). The introduction of a new "vascular score" based on the introduction of the acceleration of flow in another score system previously presented, was not able to improve the predictive performance of color Doppler analysis.Color Doppler ultrasonography of ovarian tumors seems to be a reliable method in the differential diagnosis of adnexal masses, and its potential use in the choice of a less-invasive surgical approach in selected cases (those negative to the "vascular score") should be considered.

The increasing use of analogs of Gn-RH during treatment of some benign gynaecological diseases, has induced the authors to investigate the principal collateral effects, fixing one's attention on the loss of bony mass.This perspective research has considered 38 patients selected for two diseases "endometriosis" and "uterine fibromyomatosis". The therapy has been effected with triptorelin intramuscularly in a dose of 3.75 mg every 28 days for six months, in all six phials.After a half-yearly cycle of therapy, the loss of bony mass was valued about 3% medium.In the light of other studies too, it was decided to confirm the necessity of associating other medicines able to prevent the side effects caused by their analogs of Gn-RH.

The aim of this study is to evaluate the association between GnRH analogues and ipriflavone, drug modulating the bone turnover limiting the negative bone effects of analogue. Thirty patients (33 +/- 5.4 years, mean +/- SD) affect by benign gynecological conditions in which there was an indication to use GnRH analogs have been treated with leuprolide acetate at the monthly intramuscular dose of 3.75 mg, for six months. Fifteen of these patients also received 600 mg/day per os of ipriflavone (group A), while the other 15 patients have been treated exclusively with leuprolide acetate (group B). Before and after treatment, radial bone mineral density (BMD) and main markers of bone turnover were measured in all patients. Before treatment no difference in the considered parameters could be detected between the two groups. In group A, after 6 months of treatment no significant decrease in BMD and no variations in the bone turnover parameters. On the contrary, in group B, after six months of treatment, a significant decrease (p0.05) in BMD was observed in comparison to basal and group A values. In the same group alkaline phosphatase, osteocalcin and urinary calcium/creatinine and hydroxyproline/creatinine ratio proved significantly increased in comparison to basal and group A values (both with p0.05). Ipriflavone, therefore, seems to be effective in counteracting the negative effects of GnRH-a induced on bone.

Hysteroscopy is a technique which plays a fundamental diagnostic role in gynecological practice. The possibility of obtaining a direct intracavitary view and performing specific biopsies give it a greater level of diagnostic accuracy than intrauterine curettage. The authors' personal experience of 13,923 case enables the correct method of performing this procedure to be codified in order to avoid the inherent risks and complications. The main indication is abnormal uterine bleeding which is the most frequently observed pathology in gynecological practice. In cases of metrorrhagia in women of child-bearing age benign organic pathology accounts for 45% of patients and malignant pathology 0.3%. Post-menopausal patients reveal an increase in the incidence of organic pathology in general and neoplastic pathologies in particular (8.1%). Complications linked to this type of technique are extremely rare and in overall terms affect 1% of cases. The analysis of results shows that hysteroscopy today represents an extremely reliable and repeatable outpatient procedure. However, in spite of these advantages, including savings in health costs, it is not widely used at a capillary level given that if performed by persons who are not expert it may become traumatic and unreliable. The correct execution of hysteroscopy in fact calls for dexterity acquired over time which is not conditioned by the learning of previous techniques and requires an adequate period of training.

The authors discuss the state-of-the-art of ultrasound diagnosis for pelvic swellings, with special reference to uterine and ovarian cancer. They review the applications of Eco colour Doppler in gynecological oncology and discuss the protocols for the prevention and/or early diagnosis of gynecological tumours.

The authors examine 162 cervico-vaginal smears of women in peri-menopause presenting cellular alterations (ASCUS). These patients were treated with a local topic therapy as the persistence of these alterations in 23 cases (14.2%) second level analyses were performed: gynecological visit, colposcopy and biopsy. In addition to inflammatory aspects 2 in situ carcinomas and 2 moderate dysplasias were recorded. We believe therefore that cytology could be a valid aid also in pre-menopausal women in the cervico-vaginal pathology.

To evaluate the use of UGP (urinary gonadotropin protein) as a tumor marker in gynaecologic and obstetric malignant diseases.The study was carried out in the division of Gynaecology and Obstetrics of the Ospedali Riuniti in Bergamo. 63 patients, with obstetric or gynaecologic benign or malignant diseases, entered the study. 66 healthy volunteers were examined as a group-control. In both the groups UGP levels were determined in morning urine, using an immunoenzymatic commercial kit.Results, expressed in fmol UGP/ml of urin, show that UGP is produced by several neoplasms, but the false-positive percentage is still high; a higher precision can be obtained with an accurate choice of the cut-off value and with a standardization of the analytical technics. Besides, the contemporary determination of UGP and CA 125 levels reduces the possibility of false-positive and false-negative results.More studies must be carried out to confirm the value of UGP as a tumor marker in obstetrics and gynaecology. Anyway, this recently purified protein can already be useful, in combination with the usual tumor markers, in the prompt diagnosis and management of primary neoplasms or recurrences, with a higher sensibility in comparison with traditional clinical and radiological examinations.

From January 1991 to December 1993 409 post-menopausal women were observed at the Center for the Study of Climateric Disorders of the Department of Obstetrics and Gynecology of the University of L'Aquila. The aim of the study was to evaluate the incidence of gynecologic neoplasm among this group of women. A total of 48 women at risk for malignant tumors were detected. The relationship between the climateric age and the oncologic risk is discussed.

In 1991, at the Department of Obstetrics and Gynecology of Ivrea Hospital Hysteroscopy-Microcolposcopy-Vulvoscopy center was set up in order to improve the management of the intracavitary and lower genital tract pathologies. In such center skilled specialists having attended microcolpohysteroscopy and vulvoscopy training courses in specialised institutes are employed. They continuously keep in contact with such institutes for the updating of diagnostic and therapeutic protocols. The authors present their opinions about the usefulness of this center and the results achieved.

Invasive neoplasia of female genital tract diagnosed within 1980 and 1990 are considered. Among 235 cases, 49% are endometrial cancer diagnosed prevalently (83.4%) in patients older than 55 years and in the first stage (58%). Cervical cancer represents 24% of total cases and is prevalently distributed in post menopausal patients. Ib, IIa, IIb stage are diagnosed in 65.9% of cases. Ovarian cancer represents 21% of total cases. It is diagnosed prevalently in the 5th, 6th and 7th case decade. Vulvar carcinoma is prevalently diagnosed in the 7th and 8th decade, even if it has also been recorded in several younger women.

In the last decades a new discipline of "gynaecologic oncology" has spontaneously developed in the field of obstetrics and gynaecology. In this article the authors point out the necessity of an oncologic education for the gynecologist. The gynaecologist oncologist must have a solid cultural background in general and medical oncology, radio and immunotherapy. He also must have acquired surgical experience and clinical maturity. The authors underline the important role of the "general" gynecologist who must recognize risk cases, formulate a correct pre-surgical staging in order to plan a rational therapy and take part in the follow-up. His participation is important in the care of end-stage patients.

Autologous blood transfusion, as an alternative to homologous blood, must be considered for those patients who require blood. Transfusion in gynecologic oncology surgery is often required and autologous blood transfusion has been utilized. Between January 1988 and December 1992 a total of 162 surgical procedures for gynecologic cancers were performed in the same number of patients. Of these only 102 were eligible for autologous blood transfusion as predonation. The mean age of patients was 57.8 years (range 35-81). Forty-three patients were affected with endometrial carcinoma, 31 with carcinoma of the cervix, 21 with ovarian carcinoma and 7 with vulvar cancer. Collected autologous blood units were 138 (mean 1.35 every patient). Indications for predeposited blood transfusion was given by a hemorrhage greater than 100 cc intraoperatively or hemoglobin level less than 10 g/dl until 1988 or less than 8 g/dl since 1989. Forty-eight (34.8%) of the collected units were transfused to 39 autologous donors (mean 1.2 units every patient). There was a significant difference in transfusion rate in patients: endometrium 25.8%, ovary 28%, cervix 45%, vulva 72.7%. Unused autologous blood units were discarded at the expiration date: they were 90, 65% of collected ones. In 6 patients homologous blood was necessary other than autotransfusions. Our experience demonstrates that the transfusion requirement in gynecologic cancer surgery depends on pattern of neoplasm and consequently of surgical procedure. Patients with carcinoma of the cervix and vulva are at risk for transfusion and have appropriate indications for autologous donation.(ABSTRACT TRUNCATED AT 250 WORDS)

The authors examine the role of ultrasonography in the diagnosis of gynecological post-menopausal pathologies and report the activities of the ultrasound out-patient clinic over the past 5 years. Due to the prolonged life expectation of women and consequently the growing request for gynecological examinations, increased importance has been given to the pathologies typical of this age bracket Gynecological exploration if often difficult in elderly patients leading to an increased request for ultrasonography in addition to clinical examination. Transvaginal ultrasonography allows the pelvic structures and endometrial echo-pattern to be examined with greater accuracy. During the period from 1986 to 1991 a total of 405 postmenopausal women were examined using ultrasonography out of a total of 3505 gynecological scans. Scans were performed using a 3.5 MHz suprapubic or endovaginal probe. The most frequent pathology was malignant endometrial carcinoma and the most frequent clinical symptoms was metrorrhagia. In line with findings reported in the literature, the authors underline the vital importance of carefully controlling all perimenopausal women attending an ultrasound out-patient clinic who present risk factors or metrorrhagia using integrated transabdominal and endovaginal diagnosis. The use of the endovaginal probe allows images to be obtained which are otherwise not visible using the transabdominal approach, thus permitting suspect echographic patterns to be identified. Moreover, endometrial evaluation represents an important stage of the examination. It is obvious that the endovaginal approach represents a useful diagnostic technique for screening purposes, especially in high-risk groups for endometrial pathology and ovarian cancer.

The presence of 7 human papillomavirus (HPV) types in genital condylomata acuminata (GCA) from 94 otherwise healthy women was detected by in situ hybridization, employing 3 different DNA probe cocktails (6/11, 16/18 and 31/35/51). HPV+ and HPV- GCA did not differ significantly as to the multiplicity and site of lesions, nor the prevalence of younger age, previous pregnancies or abortions, oral contraception, concurrent vaginal infection, aspecific PAP-test abnormalities and cutaneous hypo-anergy. Of note is that 13/18 HPV+ GCA (72.2%) lodged HPV types (16, 18, 31, 35, 51) which are more commonly related to dysplastic and neoplastic lesions of the female genital tract.

Eighty-one patients were submitted to gynaecological malignancy surgery in a randomized study aimed at the evaluation of the efficacy of defibrotide (40 patients) and calcium heparin (41 patients) in perioperative prophylaxis. They were randomly allocated to defibrotide group (400 mg bid im starting one day before surgery and continuing until the 7th postoperative day) or calcium heparin group (5000 IU bid sc starting two hours before surgery and continuing likewise for 7 days). No cases of DVT diagnosed by means of a Doppler CW were observed in either treatment group. Laboratory parameters have shown similar modifications in the two treatment groups. Three cases of bleeding were observed in the calcium heparin group while no cases of bleeding were detected in the defibrotide group. The results obtained suggest that defibrotide is at least as effective as calcium heparin in perioperative DVT prevention and that the former drug has a possibly better tolerability profile, due to a decisively lower tendency to bleeding.

The paper analyses the importance of Papanicolaou's test in gynecological diagnostics and reports an interesting checklist drawn up by the "Istituto Superiore di Sanità" with which all women should be familiar in order to diagnose cervical cancer at an early stage.

The role of Tumor Associated Antigens in the diagnosis of neoplasia is now actively investigated. The CA-50 antigen is known to be elevated in different types of gynecological neoplasia. In this study the CA-50 levels have been measured in 70 patients with ovarian, endometrial or cervical cancer. The data obtained show that the CA-50 levels, although elevated above normal in a high percentage of the patients studied, cannot be considered diagnostic for the presence of neoplasia.

The true risk population for uterine and ovary cancer have been studied, according to the prevalence of histerectomy and oophorectomy in the Trieste area female population. The calculation of the females at risk for these tumors permits to recalculate the incidence rates that are usually underestimated. This adjustment increases the rates in all genital tract tumors from 14% to 18%, but does not modify the relative frequency per age groups or the incidence in the temporal trends. An exception is represented from the uterine corpus cancer in which the correction of the population modifies the temporal trend for the age group over 60 years. The incidences tend in fact to increase significantly more after the adjustment.

Six cases of pelvic exenteration, performed between 1 January 1987 and 30 June 1989 in the Obstetric-Gynecological Division of the Ospedali Riuniti of Bergamo are reported. Indications, surgical methods and complications are analysed in comparison to published data. From an analysis of our data it may also be concluded that pelvic exenteration has a role in the treatment of persistent and recurrent gynecological tumors, provided that patients are carefully selected.

Today the estroprogestagen pill is the most valid method of contraception given that its benefits far outweigh its risks. The paper stresses the importance of a thorough anamnestic, clinical and laboratory examination so as to obtain correct and safe steroid contraception. The efficacy and excellent tolerance of the combined method currently make it the most widespread form of oral contraception.Oral contraceptive (OCs) of high efficacy containing estroprogestins (EP) were introduced in the 1960's and since then more than 250 million used them. Their benefits include regular menstrual cycles and protection against genital tumors. Dosage seems to be directly related to risks and benefits, therefore new types of low-dose progestins have been developed. Their mechanism of action is based on hypothalamic- hypophysic control, EP suppress the production of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Their effects are as follows: the cervical mucus becomes more viscous providing a barrier against spermatozoa, regressive (atrophy) modifications and proliferative alterations of the endometrium, and metrorrhagia induced by estrogens and amenorrhea provoked by progestins. The sequential pill requires administration of estrogens in the 1st phase and estroprogestins in the 2nd phase. They minimize physiological and hormonal effects, but the failure rate is 2-3% per woman year. Combined methods of monophasic, biphasic, and triphasic design are used from the 1st to 5th day of menstruation. They block ovulation with a high degree of efficacy, but the stimulating action of EP on the endometrium produces spotting, premature or late metrorrhagia, and amenorrhea. OCs protect against malignant epithelial tumors of the ovaries. It is estimated that 1700 ovarian carcinomas and 2000 endometrial carcinomas are averted each year by the use of the pill in the US. Endometrial cancer risk is halved by EP. 7 epidemiological studies have found no association between the pill and breast cancer, and the risk of benign mammary lesions is also reduced. Accurate anamnesis is mandatory for prescribing safe OCs including screening for coagulation, hepatic function and glycemia tests, and colposcopic examination. Smoking and the pill as well as age under 16 and over 36 increase risks. Nonetheless, the benefits of EP contraceptives outweigh the risks.

Medical therapy of genital condylomatosis seems to be the most rational strategy, since this pathology is characterised by highly frequent recurrences after destructive physical therapy alone. Successful therapy of female genital condylomatosis with methisoprinol (Viruxan), administered as ointment and/or vaginal ovules is reported. The drug proved to be efficient both in curing this viral infection and preventing its recurrences.