Pituitary block with gonadotrophin-releasing hormone antagonist during intrauterine insemination cycles: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Several randomised controlled trials (RCTs) have investigated the usefulness of pituitary block with gonadotrophin-releasing hormone (GnRH) antagonists during intrauterine insemination (IUI) cycles, with conflicting results. OBJECTIVE: The aim of the present systematic review and meta-analysis of RCTs was to evaluate the effectiveness of GnRH antagonist administration as an intervention to improve the success of IUI cycles. SEARCH STRATEGY: Electronic databases (MEDLINE, Scopus, EMBASE, Sciencedirect) and clinical registers were searched from their inception until October 2017. SELECTION CRITERIA: Randomised controlled trials of infertile women undergoing one or more IUI stimulated cycles with GnRH antagonists compared with a control group. DATA COLLECTION AND ANALYSIS: The primary outcomes were ongoing pregnancy/live birth rate (OPR/LBR) and clinical pregnancy rate (CPR). Pooled results were expressed as odds ratio (OR) or mean differences with 95% confidence interval (95% CI). Sources of heterogeneity were investigated through sensitivity and subgroups analysis. The body of evidence was rated using GRADE methodology. Publication bias was assessed with funnel plot, Begg's and Egger's tests. MAIN RESULTS: Fifteen RCTs were included (3253 IUI cycles, 2345 participants). No differences in OPR/LBR (OR 1.14, 95% CI 0.82-1.57, P = 0.44) and CPR (OR 1.28, 95% CI 0.97-1.69, P = 0.08) were found. Sensitivity and subgroup analyses did not provide statistical changes in pooled results. The body of evidence was rated as low (GRADE 2/4). No publication bias was detected. CONCLUSION: Pituitary block with GnRH antagonists does not improve OPR/LBR and CPR in women undergoing IUI cycles. TWEETABLE ABSTRACT: Pituitary block with GnRH antagonists does not improve the success of IUI cycles.

The trend of VEGF-A and PlGF in pregnant patients: a perspective case-control study on 214 women.

OBJECTIVE: The aim of this study was to measure plasmatic concentrations of vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PIGF) in pregnant women, and to evaluate their relationship with age, hormonal status, gestational age, and different diseases of pregnancy. METHODS: We selected a control group of 163 patients (96 fertile and 67 in menopause) and a group of 214 pregnant patients during the whole gestational period. VEGF-A and PlGF were assayed by ELISA and EIA methods, respectively. Statistical analysis was performed using the Mann-Whitney test. RESULTS: The control group showed mean VEGF-A and PlGF values of 89.87 pg/ml and 10.22 pg/ml, respectively; PlGF showed the highest values in menopausal patients. The group of pregnant patients showed VEGF-A values of 27.05 pg/ml and PlGF values of 231.36 pg/ml respectively, with lower (for the VEGF-A) and higher (for the PlGF) statistical significance. These values were not influenced by biological age, but were related to gestational age: VEGF-A showed a decrease and PlGF an increase particularly after the 20th gestational week. PlGF showed a statistically significant decrease compared to physiological gestation in spontaneous and threatened abortions (p < 0.0001) and in ectopic pregnancies (p < 0.0001), an increase in ultrasound and CTG alterations (p < 0.05), and threatened premature delivery and uterine hypercontractility (p < 0.01); on the other hand VEGF-A showed a statistically significant increase in ectopic pregnancies (p < 0.05). CONCLUSIONS: VEGF-A and PlGF may play a diagnostic and prognostic role in pregnancy. Further studies are required to better understand the meaning of variability of their values.

Pelvic lymphadenectomy in endometrial cancer: our current experience.

OBJECTIVE: Lymph node involvement is the single most important factor in the prognosis of endometrial cancer, because it is predictive of locoregional and distant metastases. The purpose of our study was to determine whether lymphadenectomy is useful in the surgical staging of endometrial cancer and if it may help establish a more accurate prognosis and reduce the need for postoperative therapy in patients without surgical complications. STUDY DESIGN: We conducted a retrospective study on 55 patients with diagnosis of endometrial cancer. RESULTS: Surgical staging of patients undergoing pelvic lymphadenectomy (47/55) showed that 59.6% of cases (n = 28) had Stage I cancer (IA in 4, IB in 16, IC in 8), 17.02% (n = 8) Stage II (IIA in 3, IIB in 5), 21.2% (n = 10) Stage III (IIIB in 5, IIIC in 5), and 2.1% (n = 1) Stage IVA. In the remaining eight patients with a very high anesthesiologic risk (ASA 4), surgical staging was incomplete because they underwent only node palpation. CONCLUSION: In conclusion, as we wait for the sentinel lymph node technique to demonstrate satisfactory results and be standardized also for endometrial cancer, we believe that surgical lymph node dissection plays a crucial role in debulking this type of cancer. When performed by a good surgical oncology team, it does not entail a significantly increased operative risk.

A perspective study on correlation between HPV DNA and lymph nodes in surgically treated cervical carcinoma patients. Preliminary data.

UNLABELLED: The purpose of this study was to analyze the presence of HPV DNA in lymph nodes in patients with cervical cancer. STUDY DESIGN: A prespective study was performed on a total of 18 patients with cervical cancer in FIGO Stage I-II. The surgical procedure consisted of systematic pelvic lymphadenectomy with removal of the common/external/internal (obturator) iliac lymph node chains, followed by radical hysterectomy depending on the clinical stage, or by Piver's type II radical laparohysterectomy for Stage IA2 carcinoma and Piver's type-III laparohysterectomy for Stage IB or Stage II carcinoma. After removal by a technique not yet described in the literature, the lymph nodes were processed directly in the operating room. HPV DNA testing was done using a cytobrush device. At the end of this operation, the lymph nodes were sent to the hospital's pathologist for metastasis detection. RESULTS: The correlation between a positive HPV DNA test in the cervix and lymph node metastasis was non significant (p < 0.63). By contrast, the correlation between a positive HPV DNA test in the lymph nodes and lymph node metastasis was highly significant (p < 0.005), as was the correlation between positive HPV DNA tests in the cervix and lymph nodes (p < 0.005). Finally, the correlation between disease stage and positive HPV DNA testing in the lymph nodes was also significant (p < 0.05). CONCLUSIONS: In conclusion, the technique that we used for HPV DNA extraction appears safe and reproducible. The results are comparable with, if not better, than those obtained with other techniques reported in the literature. The presence of HPV DNA in the lymph nodes is probably an early indicator of metastasis and as such it could be used as a predictor of relapse. Normally untreated patients who have this marker could then receive adjuvant therapy.

Incidence of port-site metastasis after laparoscopic management of borderline ovarian tumors: a series of 22 patients.

PURPOSE: The aim of this work was to evaluate the incidence of port-site metastasis in patients undergoing laparoscopy for borderline ovarian carcinoma (BOT). METHODS: Twenty-two patients who underwent laparoscopy from 2004 to 2008 for BOT were evaluated retrospectively. RESULTS: In 15 patients an ultraconservative procedure with enucleation of the annexal neoplasia was carried out, while in five (23%) unilateral salpingo-oophorectomy was performed and in two cases (9%) bilateral salpingo-oophorectomy was done. CONCLUSION: The literature data report few cases of port-site metastasis in BOT patients. Residual cutaneous metastases have been reported to occur within 12 months from the first surgery, generally in association with serous histology. In our analysis, we found 17 out of 22 cases of serous BOT, three mucinous and two endometriod. In no case was cutaneous metastasis revealed after an average of 30 months of follow-up.

Preterm delivery and premature rupture of membranes after conization in 80 women. Preliminary data.

AIM: Cervical intraepithelial neoplasia is most frequently in young women in reproductive age. Cold knife conization, laser ablation, laser conization and large loop excision are conservative methods of treatment to remove the transformation zone and preserve the cervical function. Previous studies have shown conflicting results on the outcomes of pregnancy following these therapies that might increase the risk of preterm delivery. The purpose of this study was to evaluate the outcome of pregnancy after conization and its role as predictive risk factor. METHODS: A retrospective study was performed. The study group comprised 80 women who had a conization and that had a subsequent singleton pregnancy. Variables considered includes maternal excision date, surgery procedure, previous surgery treatments, time interval between excisional procedure and subsequent pregnancy; duration and week of pregnancy, mode of delivery, histological grading (no cervical intraepithelial neoplasia [CIN], CIN 1, CIN 2-3) and cone excised depth. RESULTS: In group study 45 women underwent loop electrosurgical excision procedure (LEEP) conization, 32 cold knife conization and 3 laser CO2. The authors found 11 cases of cone tissue depth<1 cm, and remaining one>1 cm. Eight preterm delivery have been reported to data: 5 between 28 and 34 weeks, 2 lower than 28 weeks and 1 between 34 and 37 weeks. CONCLUSION: In these preliminary data the percentage of preterm birth appears as 10% and in range 6-15% evaluated for women not submitted to excisional procedures.

Vaginal versus abdominal hysterectomy in endometrial cancer: a retrospective study in a selective population.

The purpose of this study was to analyze the outcome of vaginal and abdominal hysterectomy for the treatment of early-stage endometrial cancer in a selected group of elder patients. This retrospective study analyzed a total of 154 patients: 113 (group I) underwent vaginal surgery and 41 (group II) underwent laparotomy. In both groups, we investigated the following parameters: intra- and postoperative complications, mean operative time, mean hospital stay, disease-free survival (DFS), overall survival (OS), and time of local or retroperitoneal recurrence. Medically compromised patients were significantly more frequent in the vaginal surgery group (P = 0.005), and the operative duration in this group was significantly shorter (P = 0.01). Intra- and postoperative complications, along with local and distant recurrence, did not show a statistically significant difference in the two groups. Total survival in the two populations, 85% at 5 years, did not reach statistically significant difference either in terms of DFS or in terms of OS. Vaginal surgery compared to traditional abdominal approach is feasible also in patients with high surgical risk; it does not require general anesthesia, abolishes abdominal trauma correlated to laparotomy, and allows a quicker reprise of the bladder and rectal function; therefore, it achieves high eradication rates and low intra- and postoperative morbidity rates.

Uterine smooth muscle tumor of uncertain malignant potential: a three-case report.

Based on the degree of cytologic atypia, mitotic activity, and other features, uterine smooth muscle tumors have historically been grouped into two classes: benign leiomyomas and malignant leiomyosarcomas. However, this separation holds true more in principle than in practice because the tumor's biological potential may not always be determined with certainty, complicating diagnosis, and therapy. We report three cases of patients with uterine smooth muscle tumors of uncertain malignant potential. Surgery was radical in two and conservative in one. During the follow-up, one patient developed diffuse lung metastases. The two other patients have not shown any signs of relapse to date. Uterine smooth muscle tumors of uncertain malignant potential may have an unpredictable clinical course and may metastasize to seemingly low-grade neoplasms in distant sites even after several years and even in the absence of important negative prognostic predictors, such as coagulative tumor cell necrosis. At present, no final consensus has been reached on the choice of the best strategy for surgery and adjuvant therapy.

Sertoli cell tumor: a rare case in an elderly patient.

Sertoli-Leydig cell tumors constitute < 1% of ovarian tumors, mostly in young women with virilization; however, not all present endocrine manifestations. A 72-year-old female presented with an abdominal mass and no signs of virilization. Total abdominal hysterectomy with bilateral salpingo-oophorectomy, omentectomy and selective pelvic lymphadenectomy was performed. The pathologic diagnosis was poorly-differentiated sex cord-stromal tumor with Sertoli cells. No adjuvant chemotherapy or radiation was administered. At 12-month follow-up the patient showed no evidence of disease.

Intraepithelial G3 adenocarcinoma of the endometrium after tamoxifen treatment.

CASE REPORT: In this paper we describe a case of endometrial carcinoma observed in a post-menopausal patient who was treated with tamoxifen for 5 years after a mastectomy for cancer. She came to our department because of vaginal bleeding 2 years after the end of tamoxifen treatment. TREATMENT: She underwent hysteroscopy and a D and C. A polypoid endometrium completely filled the uterine cavity and was carefully removed by curettage; histology showed a highly undifferentiated neoplasia with a component of serous adenocarcinoma, which was likely to originate from endometrial polyps. OUTCOME: The patient underwent radical hysterectomy, but no residual tumor was found in the uterus or in the tubes, ovary, or pelvic nodes, in spite of its low differentiation grade and high potential aggressiveness, and even though the patient was already symptomatic. Two years after surgery the patient is disease free, which is consistent with the evaluation of the surgical specimen, but unusual in poorly differentiated neoplasms.

Ultrasound-guided mammotome vacuum biopsy for the diagnosis of impalpable breast lesions.

OBJECTIVES: To assess the diagnostic accuracy of ultrasound-guided mammotome vacuum biopsy in impalpable breast lesions. METHODS: Seventy-three patients who presented with impalpable breast lesions that were suspicious for malignancy at mammography and/or sonography were included in the study. In the first instance the women underwent ultrasound-guided fine-needle aspiration cytology, then, 3 days later, histological biopsy with an ultrasound-guided mammotome device. The patients with both cytological and histological diagnoses of malignancy underwent surgery; those with a negative (for malignancy) cytological diagnosis, but with a histological diagnosis of atypical hyperplasia or sclerosing adenosis, underwent surgical biopsy. RESULTS: The diagnostic accuracy of fine-needle aspiration cytology was 67.2%; the sensitivity was 86.7%, the specificity was 48.4%, the negative predictive value was 78.9% and the positive predictive value was 61.9%. In comparison, the diagnostic accuracy of histological sampling by mammotome vacuum biopsy was 97.3%; the sensitivity was 94.7%, the specificity was 100%, the negative predictive value was 94.6% and the positive predictive value was 100%. Thus there was a statistically significant difference in diagnostic accuracy between fine-needle aspiration cytology and mammotome vacuum biopsy (67.2% vs. 97.3%; chi2 test, P < 0.001). The 2.7% (2/73) failure rate of mammotome biopsy was likely to be due to an error in the positioning of the needle. The subsequent surgical biopsy proved that two cases, negative for malignancy by mammotome biopsy, were in fact malignant. CONCLUSIONS: Our data confirm the value of sonography for the diagnosis of breast carcinoma in the preclinical phase and the efficacy of ultrasound sampling using a mammotome device to confirm the diagnosis in impalpable breast lesions.

A cytoplasmatic estrogen receptor related protein (ER-D5 Ag) in breast cancer.

A monoclonal antibody against an Estrogen Receptor Related Protein (EG-D5 AG by Amersham) was analyzed in evaluating hormone dependence in 188 breast cancers, in addition to current index of steroid receptors. The Authors observed that the concentration of this new Antigen is not related with PgR but with ER concentration. In fact, increasing the ER values, increases the concentration of ER-D5 Ag, showing a good correlation between these two tumoral markers. In regard to Progesterone Receptor ranges, the ER-D5+ves were equally distributed between PgR-ves and PgR+ves Our experience suggests the application of ER-D5 Ag as R-ves tumor screening marker and emphasizes the importance of a second level in determining therapy and prognosis in breast cancer.

ER-D5 antigen immune radiometric assay in breast cancer research.

A trial of 185 breast cancer tissues has been developed to characterize receptor negative tumors. We observed the ER-D5-Ag availability to recognize the hormone sensitivity inside the receptor-negative patient groups. In Pre-M ER--ve patients, we observed 26.9%-29.4% of D5+ve cases and in PgR--ve 50% of D5+ve cases. In Post-M ER--ve patients, we observed 31.2%-36.5% of D5+ve cases and in PgR--ve 53.2% of D5+ve cases. The reproducibility of our results suggests the relevance of an additional investigation to characterize the hormonal sensitivity of receptor-negative breast cancer tissues.

Vulvar hormonal receptor modifications during topical steroid treatment.

Four groups of 92 patients steroid pre-treated and non-treated vulvar tissues at delivery, during episiotomy, were used in determining androgen, estrogen and progesterone receptors. In 24 central specimens ER and AR concentrations turned out to be quite low when compared to the endometrium and the breast; PgR were much higher in both the cytoplasm and the nucleus, with a statistically significant difference. After estrogen, testosterone and progesterone topical treatment we observed interesting receptor status modifications which emphasize the use of vulvar receptors as marker during local therapy.

Receptor levels in breast cancer.

This report provides information regarding the relative importance of ER and PgR alone and both, as markers, in 352 breast cancers. We observed that the presence of ER not involves the presence of PgR, while the presence of PgR assumes an estrogenic action even if the lowest. In addition the presence of PgR+ depends also on ER negative-detectable (91.42% of the cases) such as we were able to observe that PgR+ was associated with ER negative-undetectable, only in 8.57% of cases. Moreover within the positivity of the couple of ER/PgR, the prognostic value is correlated at ER+ levels, while the predictive value is correlated at PgR+ levels.

Steroid receptors in benign breast disease, gross cystic disease and fibroadenoma.

The benign breast pathology embraces a wide variety of anatomo-clinical-pathological conditions producing confusion in nomenclature. The Authors collected three different types of BBP and investigated the hormonal receptor status for each. The following concentrations of ERc were found: 1-6 fmol/mg in BBD; less than 2 fmol/mg in GCD; 12-18 fmol/mg in the cytoplasm and 29-37.5 fmol/mg in the nucleus in FA. In FA, PgR was found in concentrations of 43.5-50 fmol/mg in the cytoplasm and 0.2-10 fmol/mg in the nucleus. Even if we consider these three histo-pathological entities (BBD, GCD, FA) separately, no correlation can be seen between the presence of receptors and benign breast disease. The only observation we can make is that the fibroadenomas contain more easily identifiable receptor concentrations than BBD and GCD.

Clinical considerations on the metastases of mammarian cancer.

The Authors examine the prognostic value of metastatic breast cancer and the consequent possibility of therapy. They discuss the role of steroid receptor determination both in prognosis and in planning treatment. Their personal experience confirms the positivity of Progestinic receptors as a more specific index of hormono-sensitivity in regard to the positivity of the single estrogen receptors. Concerning therapy, in metastatic breast cancer the association between chemo- and hormono-therapy may offer better results, acting on different cell populations, though it probably does not improve the survival rate.