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Risk-reducing salpingo-oophorectomy: a meta-analysis on impact on ovarian cancer risk and all cause mortality in BRCA 1 and BRCA 2 mutation carriers.

BackgroundWomen with BRCA1 and BRCA2 mutation carriers are at substantially elevated risk of developing ovarian cancer. The aim of the meta-analysis is to clarify the role of risk-reducing salpingo-oophorectomy (RRSO) to reduce ovarian cancer risk and mortality in women with BRCA 1 and BRCA 2 mutation carriers.MethodsPubmed, Medline and Scopus were searched to select English-language articles. Two investigators independently extracted characteristics and results of selected studies. Articles were included only if prospective and if absolute numbers of ovarian cancer and death events were available or derivable from the test. Pooled hazard ratio (HR) with 95% confidence interval (CI) was calculated using fixed effects model.ResultsMeta-analysis of 3 prospective studies demonstrated a significant risk reduction of ovarian cancer with RRSO in BRCA 1 and BRCA 2 mutation carriers, as well as benefit in all-causes mortality incidence.ConclusionsIt may be justified to recommend RRSO to reduce ovarian cancer risk and all-causes mortality in women with a mutation in BRCA 1 and BRCA 2.

Targeted drug delivery via folate receptors in recurrent ovarian cancer: A review

Ovarian cancer is the most common cause of gynecological cancer-related mortality, with the majority of women presenting with advanced disease; although chemotherapeutic advances have improved progression-free survival, conventional treatments offer limited results in terms of long-term responses and survival. Research has recently focused on targeted therapies, which represent a new, promising therapeutic approach, aimed to maximize tumor kill and minimize toxicity. Besides antiangiogenetic agents and poly (ADP-ribose) polymerase inhibitors, the folate, with its membrane-bound receptor, is currently one of the most investigated alternatives. In particular, folate receptor (FR) has been shown to be frequently overexpressed on the surface of almost all epithelial ovarian cancers, making this receptor an excellent tumor-associated antigen. There are two basic strategies to targeting FRs with therapeutic intent: the first is based on anti-FR antibody (ie, farletuzumab) and the second is based on folate–chemotherapy conjugates (ie, vintafolide/etarfolatide). Both strategies have been investigated in Phase III clinical trials. The aim of this review is to analyze the research regarding the activity of these promising anti-FR agents in patients affected by ovarian cancer, including anti-FR antibodies and folate–chemotherapy conjugates.

Vaginal estrogen therapy and overactive bladder symptoms in postmenopausal patients after a tension-free vaginal tape procedure: a randomized clinical trial.

Objective:To evaluate whether the frequency of overactive bladder (OAB) symptoms increases in menopause patients after a tension-free vaginal tape (TVT) procedure, and to determine if topical estrogen therapy can help prevent these symptoms. Design:After undergoing a preoperative assessment, enrolled patients were randomly allocated to receive TVT plus postoperative vaginal estrogen therapy (ET group) or TVT without adjunctive medical treatment (No ET group). The pre- and postoperative assessments included: acquisition of a urogynecologic history with standardized questions regarding urinary function (including a 10-grade visual analogue scale score), urogynecologic clinical examination, and urodynamic assessment. Follow-up assessments were performed at 1, 3, and 6 months after surgery. Results:Fifty-six of 59 patients were evaluable; 28 received topic vaginal estrogen after surgery (ET group) and 28 did not receive adjunctive medical treatment (No ET group). The overall OAB syndrome rate in menopause patients (No ET group) was 7% (2 of 28 patients) at baseline and 32% (9 of 28 patients) 6 months after surgery (P = 0.04). At the 6-month follow-up assessment, the incidence of urinary urgency was 4% (1 of 28 patients) and 29% (8 of 28 patients) in the ET and No ET groups, respectively (P = 0.01). Differences in frequency and nocturia were not statistically significant. Analysis of the visual analogue scale scores revealed that at the 6-month follow-up assessment, urgency significantly improved in the ET group compared with the No ET group (0.23 ± 1.0 vs 2.30 ± 3.7, respectively; P = 0.02). Conclusions:The TVT procedure seems to increase the frequency of OAB syndrome in menopause patients. Vaginal estriol therapy significantly reduces symptoms of urinary urgency, has a high rate of patient satisfaction, and can be used to treat postmenopausal women for at least 6 months after a TVT procedure.

Laparoscopy compared with laparoscopically guided minilaparotomy for large adnexal masses: A randomized controlled trial

OBJECTIVE: To address the efficacy in terms of intraperitoneal spillage of laparoscopically guided minilaparotomy compared with operative laparoscopy for large adnexal cysts. METHODS: A randomized controlled trial was carried out at a tertiary referral center from January 2005 to September 2006. Sixty eligible patients affected by nonendometriotic adnexal cysts with diameter between 7 and 18 cm were randomly assigned to either operative laparoscopy or laparoscopically guided minilaparotomy. RESULTS: The relative risk for intraperitoneal spillage among women treated with laparoscopy was 5.55 (95% confidence interval 1.88–16.33). Operative times were significantly shorter in patients who underwent laparoscopically guided minilaparotomy. Surgical difficulty was significantly higher in patients treated with laparoscopy. However, postoperative stay was shorter. CONCLUSION: Laparoscopically guided minilaparotomy, when compared with laparoscopy, is able to reduce intraperitoneal spillage in patients with presumably benign large adnexal masses, with minimal increase in patient short- and long-term discomfort. Because data regarding the importance of intraperitoneal spillage during surgery for benign and malignant pathologies, as well as rupture rates during traditional laparotomy, are scarce, traditional laparotomy still represents the standard treatment. In women desiring a minimally invasive strategy for large cysts, laparoscopically guided minilaparotomy should be considered. CLINICAL TRIAL REGISTRATION: Australian Clinical Trials Registry, www.actr.org.au, ACTRN012607000241437 LEVEL OF EVIDENCE: I

Simple extrafascial trachelectomy and pelvic bilateral lymphadenectomy in early stage cervical cancer.

OBJECTIVE To determine the feasibility and safety of simple extra-fascial trachelectomy plus pelvic lymphadenectomy in young patients affected by early stage cervical cancer. METHODS We have prospectively identified all patients with early-stage cervical cancer (stages IA2-IB1) referred to our department. Inclusion criteria were: age ≤ 38 years, strong desire to maintain fertility, FIGO stage ≤ IB1, tumor size<2 cm, no LVSI, no evidence of nodal metastasis. Surgical technique included two steps: laparoscopic pelvic lymphadenectomy and vaginal simple extrafascial trachelectomy. Patients were followed up for oncological and obstetrical outcomes. RESULTS Fourteen patients were enrolled in the study. Median age was 32 years (range 28-37); histotype was squamous in 11/14 (79%) cases and adenocarcinoma in 3/14 cases (21%); FIGO stage was IA2 in 5/14 (36%) patients, IB1 in 9/14 (64%) patients; median tumor size was 17 mm (range 14-19); median operative time was 120 min (range 95-210). No severe intraoperative complications were recorded. Postoperative complications were observed in two patients. No recurrences were detected. One patient died for other disease. Eight patients became pregnant and 3 of them had a term delivery. CONCLUSION Low risk early-cervical cancer patients could be safely treated by simple extrafascial trachelectomy in order to maintain fertility. More studies are needed to better define the role of conservative and ultraconservative surgical approaches (i.e. conization) in this setting, either for fertility purposes or to minimize surgical complications.

Update on lymphadenectomy in early and advanced ovarian cancer

Purpose of review Pelvic and para-aortic lymphnode sampling is an integral part of the staging system of ovarian cancer. The issue concerning lymphadenectomy in the management of the disease is still debated, however. The purpose of this paper is to review the role of systematic lymphadenectomy in patients affected by early and advanced-stage ovarian cancer. Recent findings Some retrospective studies have revealed an increased survival rate in early-stage ovarian cancer patients after lymphadenectomy. Recently, the first randomized prospective trial, on lymphadenectomy in advanced-stage disease, was published. It evidenced an improvement in progression-free survival in patients who had undergone lymphadenectomy. Summary Systematic lymphadenectomy has a diagnostic value in early-stage ovarian cancer, thanks to the possibility of accurate clinical staging. As up to 22% of women, who were presumed to have early-stage ovarian cancers, are upstaged during the lymphadenectomy procedure, accurate staging can help to avoid unnecessary postoperative chemotherapy. In patients affected by advanced ovarian cancer, systematic lymphadenectomy statistically significantly improves progression-free survival and reduces recurrence rates despite a higher incidence of postoperative complications. As improvement of overall survival is not statistically significant, further studies are needed to balance risks and benefits of systematic lymphadenectomy in advanced-stage disease.

Immunotherapy of Ovarian Cancer: The Role of Checkpoint Inhibitors

Ovarian cancer is the most important cause of gynecological cancer-related mortality, with the majority of women presenting with advanced disease. Although surgery and chemotherapy can improve survival rates, it is necessary to integrate alternative strategies to improve the outcomes. Advances in understanding the role of immune system in the pathogenesis of cancer have led to the rapid evolvement of immunotherapy, which might establish a sustained immune system response against recurring cancer cells. Recently, it has emerged that powerful immunologic effector cells may be blocked by inhibitory regulatory pathways controlled by specific molecules often called “immune checkpoints,” which turn off the immune system. Similarly, cancer cells are able to use these checkpoints to avoid immune control and rejection. Inhibition of these inhibitory pathways represents a potent strategy in the fight against cancer and is currently under investigation with encouraging results in some cancers, such as melanoma. In ovarian cancer researches are still in an early phase, but with promising results. In this review we will explore the rationale of immunotherapy in ovarian cancer with a special focus on these emerging molecules.

Olaparib, PARP1 inhibitor in ovarian cancer

Introduction: Ovarian cancer is the most important cause of gynecological cancer-related mortality. Conventional treatments for advanced or recurrent disease offer limited results in terms of long-term responses and survival. Researches have recently focused on target therapies, which represent a new, promising, therapeutic approach, able to maximizing tumor kill and minimizing toxicity. The family of polyadenosine diphosphate-ribose polymerase (PARP) inhibitors is currently one of the most hopeful and investigated alternatives. Areas covered: Preclinical and clinical studies of Olaparib, the most investigated PARP inhibitor in ovarian cancer, are analyzed and discussed. Data were obtained by searching for all English peer-reviewed articles on Medline, on Cochrane Database and all on-going Phase I and II studies registered on National Cancer Institute Clinical Trials; also any related abstracts recently presented on Olaparib at major international congresses will be included. Expert opinion: Bad prognosis and drug resistance usually affect ovarian cancer. Recent trends toward the knowledge of molecular-specific pathways have produced new target drugs. PARP inhibition mediated by Olaparib in BRCA1 (breast cancer 1) and BRCA2 (breast cancer 2)-mutated and in sporadic ovarian cancer represents a promising field of investigation. Further studies are needed to confirm initial exciting results.

Hormone therapy in oophorectomized BRCA1/2 mutation carriers.

ObjectiveBRCA1/2 mutation carriers have greatly elevated lifetime risks of breast, ovarian, and fallopian tube cancers. Bilateral prophylactic salpingo-oophorectomy is recommended to prevent cancer in these women. As it is often performed before natural menopause, it may be accompanied by menopausal symptoms, impaired quality of life, and increased cardiovascular risk. MethodsIn this review, we describe the indications, timing, and implications of salpingo-oophorectomy for BRCA-positive women, with a special focus on the risks and benefits of hormone therapy (HT). Furthermore, retrospective and prospective trials of HT in BRCA mutation carriers undergoing prophylactic salpingo-oophorectomy are debated. ResultsHormonal deprivation after prophylactic salpingo-oophorectomy may negatively impact health and quality of life; most women experience menopausal symptoms shortly after surgical operation. Literature data suggest that HT generally reduces vasomotor symptoms related to surgical menopause, improving sexual functioning without affecting survival. ConclusionsDespite the limitations of retrospective and prospective observational studies, short-term HT seems to improve quality of life and does not seem to have an adverse effect on oncologic outcomes in BRCA1 and BRCA2 mutation carriers without a personal history of breast cancer. Therefore, randomized and larger trials are urgently needed.

continuous versus cyclic oral contraceptives after laparoscopic excision of ovarian endometriomas: a systematic review and metaanalysis

In the lack of evidence consistently supporting the use of continuous vs cyclic oral contraceptives after surgery for endometriosis, we conducted a systematic review and metaanalysis with the objective of comparing a continuous vs a cyclic oral contraceptive schedule administered after surgical excision of ovarian endometriomas. A PubMed, MedLine, and Embase search through December 2014 was conducted, with the use of a combination of key words and text words related to endometrioma, endometriosis, oral contraceptives, oral estroprogestins, laparoscopy, and surgery. Studies directly comparing a continuous vs a cyclic schedule administered after surgical treatment of endometriomas were included, with pain and endometrioma recurrence rates as the primary outcomes. Three reviewers independently assessed methodology and extracted data from selected studies. The primary outcomes were considered pain recurrence (evaluated separately for dysmenorrhea, noncyclic chronic pelvic pain, and dyspareunia) and endometrioma recurrence evaluated at ultrasonography. Dichotomous outcomes from each study were expressed as risk ratio (RR) with a 95% confidence interval (CI). Three randomized clinical trials and 1 prospective controlled cohort study were included, for a total of 557 patients with endometriosis, 343 patients of whom had ovarian endometriomas completing the assigned treatment and follow-up. Lower recurrence rates for dysmenorrhea were obtained with a continuous schedule (RR, 0.24; 95% CI, 0.06-0.91; P = .04). Nonsignificant differences were present for chronic pelvic pain and dyspareunia. A continuous oral contraceptive schedule was associated with a nonsignificant reduction of cyst recurrence rates compared with a cyclic schedule (RR, 0.54; 95% CI, 0.28-1.05; P = .07). A continuous oral contraceptive regimen, as opposed to a cyclic regimen, may be suggested after surgery for endometriomas because of lower dysmenorrhea recurrence rates. Due to the small number and small sample sizes of the included studies, further randomized clinical trials are needed to confirm the findings of the present systematic review. Also, outcomes related to patient satisfaction and quality of life should be addressed.