Life Experience of Survivors of Gynecologic Cancers: A Survey Conducted in Italy.

BACKGROUND: The study of health-related quality of life in survivors of gynecologic cancers is becoming increasingly important as 1.5 million survivors of gynecologic cancer in the United States and more are expected due to advances in diagnosis and treatment. This project investigated the perceived needs and lived experiences of survivors of gynecological cancer to help design supportive activities to be implemented in clinical practice. METHODS: Patients were recruited in hospitals or through social media and responded to an online survey that was addressed to patients in Italy, specifically in Sicily, Puglia, and Campania. Patients with ovarian, endometrium, or cervix cancer were recruited among women attending Cannizzaro Hospital and Alleanza Contro il Tumore Ovarico (Alliance Against Ovarian Cancer) members. RESULTS: Body image perception was changed in 82.3% of respondents, whereas familial relationships were described as changed by 27.5% of women. In 69.6% of patients, sexual habits were hindered by changes in the body, depression, pain, and awkwardness. Physicians informed patients about sexuality changes related to cancer extensively in 16.7% of cases and briefly in 19.6% of cases. The advice of a clinical sexologist was considered potentially helpful by 31.4% of patients and not potentially helpful by 47.1%, whereas 21.6% of patients had no opinion. CONCLUSIONS: Although sexual habits are often changed by cancer, women surviving gynecological cancer rarely seek medical advice in this area. Physicians should be trained to inform patients and to promote referrals to sexologists.

A review and metanalysis of metronomic oral single-agent cyclophosphamide for treating advanced ovarian carcinoma in the era of precision medicine.

OBJECTIVE: Oral metronomic cyclophosphamide has been used as a single agent or in combination with other drugs for several solid tumors with interesting results in disease palliation and mild to moderate toxicity, notably in patients with recurrent epithelial ovarian cancer (EOC) progressing after systemic chemotherapy. In this paper, we report a review and a metanalysis of heterogeneous data published up to date. DATA SOURCES: The literature search was restricted to single-agent MOC. The analysis was conducted through March 2023 by consulting PubMed, Embase, Google Scholar, and The Cochrane Library databases. Research string and Medical Subject Headings included "ovarian tumor," "ovarian carcinoma," or "ovarian cancer," "fallopian tube cancer," "primary peritoneal cancer," "oral chemotherapy," and "metronomic cyclophosphamide." All articles were assessed for quality by at least two investigators independently, and a < 18 patients sample size cutoff was chosen as a lower limit with a Cohen's kappa statistical coefficient for accuracy and reliability. Metanalysis of selected papers was carried out according to a fixed model. DATA SUMMARY: The percentage of agreement between investigators on literature study selection was very high, reaching 96.9% with a Cohen's k of 0.929. MOC pooled objective response rate (ORR) and disease control rate for recurrent or platinum-refractory ovarian cancer were 18.8% (range 4-44%) and 36.2% (range 16-58.8%), respectively. The mean progressive-free survival and overall survival were 3.16 months (range 1.9 to 5.0 months) and 8.7 months (range 8 to 13 months), respectively. The fixed model metanalysis of selected studies showed a 16% median ORR (12-20% CI, p < 0.001). CONCLUSIONS: Single-agent oral cyclophosphamide in EOC holds promise as a treatment option, even in the era of precision medicine. Genetic factors, such as DNA repair gene polymorphisms, may influence treatment response. Combining cyclophosphamide with biological agents such as PARP inhibitors or immunotherapy agents is an area of active investigation.

Dilatation and Curettage after Uterine Artery Embolization versus Methotrexate Injection for the Treatment of Cesarean Scar Pregnancy: A Single-Center Experience.

Background and Objectives: Cesarean scar pregnancy (CSP) represents a type of ectopic pregnancy in which the embryo implants inside the scar of a previous cesarean section. This condition can lead to maternal morbidity and mortality. The best therapeutic approach in terms of clinical effectiveness and patient safety for CSP has not been described yet, although different therapeutic strategies are currently available. The purpose of the present study was to analyze the success rate of two different treatments in a single institution. Materials and Methods: A retrospective study was performed among patients diagnosed with CSP at the Gynecology and Obstetrics Department of the "Cannizzaro" Hospital in Catania (University of Enna-Italy) from January 2016 to December 2022. The diagnosis was made by 2D/3D transvaginal ultrasound, following Timor-Tritsch criteria. Two treatment strategies were performed: local and systemic methotrexate (MTX) injection and uterine artery embolization (UAE) with subsequent dilatation and curettage (D&C). All treated women underwent subsequent clinical and sonographic follow-up. Complete recovery was defined as the reduction of ß-HCG values until it was undetectable and the disappearance of the mass in the uterine scar on ultrasound. Results: Nineteen patients were included; nine were in the MTX group and ten were in the UAE + D&C group. No significant differences were found between the two groups in terms of clinical parameters. Treatment was successful in 4 of 10 (44%) patients in the MTX group and 10 of 10 (100%) in the UAE + D&C group (p = 0.01); the length of hospital stay was significantly shorter in the latter group (p < 0.0001). Conclusions: In our experience, administration of MTX is not recommended as the primary treatment or pre-treatment. Dilatation and curettage after uterine artery embolization are better than methotrexate injection for the treatment of cesarean scar pregnancy in a single-institution series in terms of complete recovery and length of hospital stay.

Cumulative Sum Analysis of Learning Curve Process for Vaginal Natural Orifice Transluminal Endoscopic Surgery Hysterectomy.

STUDY OBJECTIVE: This study aimed to evaluate the learning curve of vaginal natural orifice transuminal endoscopic surgery (vNOTES) hysterectomy in expert minimal invasive and vaginal surgery team. DESIGN: This is a cohort study on a retrospective analysis. SETTING: Department of Obstetrics and Gynecology of Cannizzaro Hospital in Catania Italy. PATIENTS: First 50 women underwent vNOTES hysterectomy between February 2021 and February 2022. INTERVENTION: vNOTES hysterectomy performed by a team with optimal skills in laparoscopic and vaginal surgery. MEASUREMENT AND MAIN RESULTS: Primary outcome was surgical time. Secondary outcomes were intraoperative and postoperative complications, length of hospitalization, and first 24-hour postoperative pain. All patients underwent hysterectomy for benign indications: 27 fibromatosis, 13 metrorrhagia, and 10 precancerous. Concomitant procedures have been bilateral adnexectomy in 35 cases and bilateral salpingectomy in 15 cases. The median age was 51 years (range, 42-64). Median body mass index was 26 kg/m2 (range, 21-42). The median operative time was 75 minutes (range, 40-110). The median hospital stay was 2 days (range, 1-4). There was 1 intraoperative adverse event (bladder lesion) and 1 postoperative grade 3 complication (hemoperitoneum). The median visual analog scale score for pain assessment during the first 24 hours after surgery was 3 (range, 1-6). The experience in our surgical center with the first 25 vNOTES hysterectomies showed an accumulation of initial experience in the first 5 cases with stable operating time and a gradual reduction of mean operating time in the subsequent 17 surgeries. The learning curve plotted by cumulative sum analysis shows 3 phases: phase 1 of competence (cases 1-5), phase 2 of proficiency (cases 6-26), and phase 3 of mastering the procedure (after the 31st case) with the management of more complex cases. CONCLUSION: vNOTES hysterectomy is a feasible and reproducible approach for benign indications with a short learning curve and low rate of perioperative complications. For a team skilled in minimally invasive surgery, 5 cases are required to rich competence and 25 to rich proficiency in vNOTES hysterectomy. Mastering phase, with the introduction of more complex cases, should be addressed after 30 surgeries.

A retrospective, real-life analysis of metronomic oral single-agent cyclophosphamide for the treatment of platinum-pretreated advanced ovarian carcinoma in Italy.

INTRODUCTION: Metronomic oral cyclophosphamide (MOC) presents many potential advantages, such as significantly less severe side effects than standard regimens, ease of administration, and the delivery of a dose-dense but not necessarily dose-intense treatment. These observations prompted us to evaluate in a retrospective, multicenter study the efficacy and toxicity of MOC in a real-life series of pretreated cancer patients. METHODS: The study is a multicenter, retrospective analysis of the activity of single-agent MOC in patients with recurrent or residual epithelial ovarian, fallopian tube, or primary. Eligible patients were continuously treated with MOC at 50 mg/day until progression, toxicity, or death. Overall response rate (ORR), stable disease (SD), and disease control rate (DCR) were reported. RESULTS: The study included 62 patients. Three patients reached a complete response rate (5%), 11 had a partial response rate (18), and 15 had stabilization of disease (24) for an ORR of 23% and a DCR of 47%. Patients with low-grade indolent tumors showed an ORR and an SD rate higher than that observed in non-indolent ones (33% vs. 18% and 28% vs. 14%, respectively). Overall, progression-free survival was 3.5 months (range 1-9 months). CONCLUSION: Single-agent MOC is active and very well tolerated in a significant fraction of patients with refractory, recurrent, or residual epithelial ovarian, fallopian tube, or primary peritoneal cancer. In the vision of a practical approach, single-agent MOC may be a useful palliative treatment option for patients with poor tolerance to high-dose regimens or widely pretreated. Further studies are needed better to characterize the role of such an approach in clinical practice.

Homologous Recombination Deficiency (HRD) Scoring, by Means of Two Different Shallow Whole-Genome Sequencing Pipelines (sWGS), in Ovarian Cancer Patients: A Comparison with Myriad MyChoice Assay.

High-grade serous ovarian cancer (HGSOC) patients carrying the BRCA1/2 mutation or deficient in the homologous recombination repair system (HRD) generally benefit from treatment with PARP inhibitors. Some international recommendations suggest that BRCA1/2 genetic testing should be offered for all newly diagnosed epithelial ovarian cancer, along with HRD assessment. Academic tests (ATs) are continuously under development, in order to break down the barriers patients encounter in accessing HRD testing. Two different methods for shallow whole-genome sequencing (sWGS) were compared to the reference assay, Myriad. All these three assays were performed on 20 retrospective HGSOC samples. Moreover, HRD results were correlated with the progression-free survival rate (PFS). Both sWGS chemistries showed good correlation with each other and a complete agreement, even when compared to the Myriad score. Our academic HRD assay categorized patients as HRD-Deficient, HRM-Mild and HRN-Negative. These three groups were matched with PFS, providing interesting findings in terms of HRD scoring and months of survival. Both our sWGS assays and the Myriad test correlated with the patient's response to treatments. Finally, our AT confirms its capability of determining HRD status, with the advantage of being faster, cheaper, and easier to carry out. Our results showed a prognostic value for the HRD score.

Uterosacral Ligament Suspension Sec Shull by Vaginal Natural Transluminal Endoscopic Surgery (vNOTES).

This step-by-step video demonstrates the feasibility of the Shull technique via vaginal natural transluminal endoscopic surgery (vNOTES) in a patient experiencing pelvic organ prolapse (POP) with apical support loss. A 51-year-old woman with apical pelvic organ prolapse quantification (POP-Q) stage III and a right benign ovarian cyst underwent a total hysterectomy and bilateral adnexectomy with vaginal dome uterosacral ligament suspension performed via vNOTES. Total operating time was 82 minutes, with negligible blood loss. The patient remained in hospital for 2 days. There were no intra- or postoperative complications at 30 days post-surgery, and there was complete repair of the apical defect at 6-month follow-up. The advantages of NOTES include avoiding abdominal incisions, eliminating complications associated with the trocar sound, and reducing postoperative pain and length of hospital stay. vNOTES provides safe entry, easy access, and direct visualization of the peritoneal cavity and pelvic anatomy. The Shull technique by vNOTES is technically feasible and permits clear and safe identification of uterosacral ligaments.

Down-regulation of long non-coding RNAs in reproductive aging and analysis of the lncRNA-miRNA-mRNA networks in human cumulus cells.

PURPOSE: Long non-coding RNAs (lncRNAs) control gene expression at multiple levels. By interacting with microRNAs (miRNAs), they regulate their mRNA targets creating dynamic regulatory networks involved in different cellular processes. Their role in follicle development and oocyte maturation has recently emerged. lncRNA deregulation has been found associated with different pathological conditions. In this study, we identified differentially expressed lncRNAs in cumulus cells (CCs) isolated from MII oocytes of advanced maternal age women and proposed ceRNA-networks involved in signaling pathways crucial in ovarian folliculogenesis and female germ cell maturation. METHODS: We performed a high-throughput analysis of the expression profile of 68 lncRNAs from CCs of aged and young women by using NanoString technology. By miRNet, TarPmiR, miRTarBase, OKdb, and KEGG we predicted some ceRNA-networks involving the differentially expressed (DE) lncRNAs, miRNA interactors, and their mRNA target genes. RESULTS: We identified 28 lncRNAs down-regulated in CC samples from aged women. The analysis revealed that the miRNAs binding 11 of the DE lncRNAs and their mRNA targets are included in ceRNA-networks involved in the regulation of the PI3K-Akt, FOXO, and p53 signaling pathways. CONCLUSION: We proposed that the lncRNA down-regulation in CCs from aged women could influence the expression of genes encoding proteins deregulated in reproductive aging. A better understanding of the interplay of lncRNA-miRNA-mRNA networks in human CCs could increase our knowledge about the mechanisms of regulation of gene expression involved in aging, lead to the development of novel therapeutics, and improve reproductive outcomes in aged women.

Progression Free Survival, Overall Survival, and Relapse Rate in Endometrioid Ovarian Cancer and Synchronous Endometrial-Ovarian Endometrioid Cancer (SEO-EC): Results from a Large Retrospective Analysis.

Background and Objectives: We aimed to evaluate Progression Free Survival (PFS), Overall Survival (OS), and relapse rate in women affected by endometrioid ovarian cancer and synchronous endometrial-ovarian endometrioid cancer (SEO-EC). As secondary outcome, we assessed whether systematic pelvic and para-aortic lymphadenectomy could be considered a determinant of relapse rate in this population. Materials and Methods: We performed a retrospective analysis of women with diagnosis of endometrioid ovarian cancer or SEO-EC between January 2010 to September 2020, and calculated PFS, OS and relapse rate. Results: In almost all the patients (97.6%) who underwent systematic pelvic and para-aortic lymphadenectomy, there were no lymph node metastases confirmed by histology. We did not find a significant difference (p = 0.6570) for the rate of relapse in the group of women who underwent systematic pelvic and para-aortic lymphadenectomy (4/42; 9.5%) compared with the group of women who did not undergo the same procedure (1/21; 4.8%). During a median follow-up was 23 months, both PFS and OS were excellent. Conclusions: Women affected by early-stage low-grade endometrioid cancer and SEO-EC without apparent lymph node involvement at pre-operative imaging showed a very low rate of lymph node metastasis and similar relapse rate with or without lymphadenectomy.

Molecular profiling of follicular fluid microRNAs in young women affected by Hodgkin lymphoma.

RESEARCH QUESTION: Treatments for Hodgkin lymphoma have improved but one of their common effects is gonadal toxicity, which contributes to fertility damage of patients and induces temporary or irreversible loss of fertility. Could micro-RNA (miRNA) expression profiles in follicular fluid be influenced by Hodgkin lymphoma? Could their alteration affect molecular pathways involved in follicle growth and oocyte maturation? DESIGN: miRNA expression profile was investigated in follicular fluid samples from young women affected by Hodgkin lymphoma compared with healthy controls by NanoString technology. Bioinformatic analysis was used to verify miRNA involvement in follicle development and miRNA deregulation with Hodgkin lymphoma in a larger cohort of follicular fluid samples was confirmed by real-time quantitative polymerase chain reaction. RESULTS: Thirteen miRNAs are deregulated in Hodgkin lymphoma samples compared with controls and are involved in molecular pathways related to cancer, gametogenesis and embryogenesis. Among them, let-7b-5p, miR-423-5p, miR-503-5p, miR-574-5p and miR-1303 are implicated in biological processes related to follicle development and oocyte maturation. Let-7b-5p holds the central position in the regulatory network of miRNA-mRNA interactions, has the highest number of mRNA target genes shared with the other differentially expressed miRNAs and is significantly downregulated in Hodgkin lymphoma follicular fluid samples. CONCLUSIONS: These data led us to question the potential influence of miRNA deregulation on oocyte quality. Further studies are needed to verify the reproductive potential of young patients with Hodgkin lymphoma before starting chemotherapy protocols and an adequate protocol of fertility preservation needs to be guaranteed.

Cytoreductive surgery followed by chemotherapy and olaparib maintenance in BRCA 1/2 mutated recurrent ovarian cancer: a retrospective MITO group study.

INTRODUCTION: The role of cytoreductive surgery in the poly-ADP ribose polymerase inhibitors era is not fully investigated. We evaluated the impact of surgery performed prior to platinum-based chemotherapy followed by olaparib maintenance in platinum-sensitive BRCA-mutated recurrent ovarian cancer. METHODS: This retrospective study included platinum-sensitive recurrent ovarian cancer BRCA-mutated patients from 13 Multicenter Italian Trials in Ovarian cancer and gynecological malignancies centers treated between September 2015 and May 2019. The primary outcomes were progression-free survival and overall survival. Data on post-progression treatment was also assessed. RESULTS: Among 209 patients, 72 patients (34.5%) underwent cytoreductive surgery followed by platinum-based chemotherapy and olaparib maintenance, while 137 patients (65.5%) underwent chemotherapy treatment alone. After a median follow-up of 37.3 months (95% CI: 33.4 to 40.8), median progression-free survival in the surgery group was not reached, compared with 11 months in patients receiving chemotherapy alone (P<0.001). Median overall survival was nearly double in patients undergoing surgery before chemotherapy (55 vs 28 months, P<0.001). Post-progression therapy was assessed in 127 patients: response rate to chemotherapy was 29.2%, 8.8%, and 9.0% in patients with platinum-free interval >12 months, between 6 and 12 months, and <6 months, respectively. CONCLUSION: Cytoreductive surgery performed before platinum therapy and olaparib maintenance was associated with longer progression-free survival and overall survival in BRCA-mutated platinum-sensitive relapsed ovarian cancer patients. In accordance with our preliminary results, the response rate to chemotherapy given after progression during olaparib was associated with platinum-free interval.

Thromboembolic events and antithrombotic prophylaxis in advanced ovarian cancer patients treated with bevacizumab: secondary analysis of the phase IV MITO-16A/MaNGO-OV2A trial.

INTRODUCTION: The use of routine antithrombotic prophylaxis is not recommended for advanced cancer patients receiving chemotherapy. The effect of bevacizumab-containing therapy on the risk of thromboembolic events remains controversial in ovarian cancer patients. We report on the incidence of thromboembolic events and the prevalence of antithrombotic therapy in patients enrolled in the single arm, phase IV, MITO-16A/MaNGO-OV2A trial. METHODS: In this trial, potential prognostic factors for patients with previously untreated ovarian cancer receiving a combination of platinum-based chemotherapy and bevacizumab were explored and the final analysis has already been reported. In this secondary analysis, the occurrence of thromboembolic events and the use of antithrombotic therapy were described according to the clinical characteristics of the patients. The prognostic role of thromboembolic events for progression-free and overall survival were also evaluated. RESULTS: From October 2012 to November 2014, 398 eligible patients were enrolled. 76 patients (19.1%) were receiving some type of anticoagulant or anti-aggregant treatment at baseline. Overall, 24 thromboembolic events were reported (cumulative incidence of 6.0%). The occurrence of thromboembolic events was not associated with baseline patient characteristics and was not modified by the use of antithrombotic prophylaxis (HR 0.60, 95% CI 0.18 to 2.0). Occurrence of thromboembolic events was not associated with progression-free survival (HR 1.34, 95% CI 0.83 to 2.15) or overall survival (HR 0.78, 95% CI 0.37 to 1.61). CONCLUSIONS: In our study, a 6.0% rate of thromboembolic events was reported during treatment with bevacizumab plus chemotherapy. Thromboembolic events were not associated with the clinical characteristics of the patients or with the use of antithrombotic prophylaxis, nor did they significantly affect the long-term prognosis. TRIAL REGISTRATION NUMBER: NCT01706120.

Bevacizumab, carboplatin, and paclitaxel in the first line treatment of advanced ovarian cancer patients: the phase IV MITO-16A/MaNGO-OV2A study.

OBJECTIVE: To explore the clinical and biological prognostic factors for advanced ovarian cancer patients receiving first-line treatment with carboplatin, paclitaxel, and bevacizumab. METHODS: A multicenter, phase IV, single arm trial was performed. Patients with advanced (FIGO (International Federation of Gynecology and Obstetrics) stage IIIB-IV) or recurrent, previously untreated, ovarian cancer received carboplatin (AUC (area under the curve) 5), paclitaxel (175 mg/m2) plus bevacizumab (15 mg/kg) on day 1 for six 3-weekly cycles followed by bevacizumab single agent (15 mg/kg) until progression or unacceptable toxicity up to a maximum of 22 total cycles. Here we report the final analysis on the role of clinical prognostic factors. The study had 80% power with a two-tailed 0.01 α error to detect a 0.60 hazard ratio with a factor expressed in at least 20% of the population. Both progression-free and overall survival were used as endpoints. RESULTS: From October 2012 to November 2014, 398 eligible patients were treated. After a median follow-up of 32.3 months (IQR 24.1-40.4), median progression-free survival was 20.8 months (95% CI 19.1 to 22.0) and median overall survival was 41.1 months (95% CI 39.1 to 43.5). Clinical factors significantly predicting progression-free and overall survival were performance status, stage, and residual disease after primary surgery. Neither baseline blood pressure/antihypertensive treatment nor the development of hypertension during bevacizumab were prognostic. There were two deaths possibly related to treatment, but no unexpected safety signal was reported. CONCLUSIONS: Efficacy and safety of bevacizumab in combination with carboplatin and paclitaxel and as maintenance were comparable to previous data. Hypertension, either at baseline or developed during treatment, was not prognostic. Performance status, stage, and residual disease after primary surgery remain the most important clinical prognostic factors. TRIAL REGISTRATION NUMBER: EudraCT 2012-003043-29; NCT01706120.

Front-line chemo-immunotherapy with carboplatin-paclitaxel using oregovomab indirect immunization in advanced ovarian cancer: A randomized phase II study.

BACKGROUND: This randomized phase II study tested the hypothesis that schedule dependent chemo-immunotherapy with oregovomab improves progression free survival (PFS) and overall survival (OS) in optimally resected, Stage III/IV ovarian cancer. METHODS: Patients from both academic centers and private practice in the US and Italy with Stage III/IV optimally cytoreduced ovarian cancer were randomized to standard six cycle IV carboplatin-paclitaxel chemotherapy (CP) versus CP plus four immunizations with oregovomab (CPO). A translational assessment of a cellular immune response was the primary endpoint; PFS and OS were measured as secondary endpoints. FINDINGS: 97 patients at thirteen centers were accrued to the protocol, 47 to CPO and 50 to CP. Technical issues led to inconsistent performance of the primary CA125 ELISPOT leading to unevaluable results. At a median follow up of 42 months, PFS and OS outcomes revealed an unexpectedly large treatment effect for CPO relative to CP alone, with median PFS of 41.8 months (95% C.I.: 21.8 - N.E.) for CPO and 12.2 months (10.4-18.6) for CP (p = 0.0027, HR 0.46, CI 0.28-0.7). For OS, the median for CPO has not yet been reached (NE) (45.2-NE) and for CP was 43.2 months (31.8-NE) (p = 0.043, HR 0.35, CI 0.16-0.74). The oregovomab treatment resulted in no change in toxicity profile from CP. INTERPRETATION: The previously identified potential clinical benefit of IV CP when administered with oregovomab was further refined in this randomized phase II study. Increases of PFS and OS of statistically and clinically significant magnitude were evident in this study of a front line chemo-immunotherapy treatment of ovarian cancer.

Olaparib as maintenance therapy in patients with BRCA 1-2 mutated recurrent platinum sensitive ovarian cancer: Real world data and post progression outcome.

OBJECTIVES: Olaparib is approved as maintenance therapy in patients with BRCA mutated platinum sensitive (PS) recurrent ovarian cancer (OC) after response to last platinum based therapy. Few data are available regarding the use out of the registration trials and on response to further treatments after progression. MATERIALS AD METHODS: In this non interventional, retrospective study, patients treated with olaparib in 13 centers, according to the label, have been collected and analyzed. Primary objectives of the study are to describe effectiveness and safety of olaparib in a real world setting with a focus on post progression treatments and response. RESULTS: 234 patients were analyzed. All patients were BRCA mutated and most of them had germline mutations. Around 50% of the patients received olaparib after 3 or more lines of platinum based chemotherapy achieving a radiologic complete (CR) or partial response. 12.4% patients with stable disease were also included. Median PFS was 14.7 months (95% CI:12.6-18), with statistically longer PFS in patients with normal serum Ca125 at baseline, a CR after last platinum based therapy and that received olaparib after second platinum based therapy. Median OS was not reached. Most frequent G3-G4 toxicity was anaemia (6%) with dose discontinuation and dose reduction in 11 (4.7%) and 49 (20.9%) of cases, respectively. Among 66 patients receiving further treatment after olaparib progression and evaluable for response, ORR was 22.2, 11.1% and 9.5% in patients with Platinum Free interval (PFI) of more than 12 months, between 6 and 12 months and less than 6 months, respectively. CONCLUSIONS: Olaparib is effective and safe in real world setting. Data on post-progression treatments seem to suggest cross resistance with chemotherapy and need to be confirmed in larger studies because of the potential importance in clinical practice decisions.

Prognostic factors and surgical treatment in vulvar carcinoma: Single center experience.

AIM: Vulvar carcinoma represents 3-5% of all female genital cancers; the main surgical treatment is radical vulvectomy and inguinal lymphadenectomy. The aim of this study is to analyze prognostic factors in the patients underwent to primary surgery for vulvar carcinoma. METHODS: One hundred and eighteen cases of vulvar carcinoma underwent surgery between 2006 and 2016 at Operative Unit of Gynecology and Obstetrics of Cannizzaro Hospital (Catania, Italy) were retrospective analyzed. Risk factors for relapse (age, tumor size, FIGO stage, type of surgery, lymphadenectomy, margins status, metastatic nodes and radiotherapy) were evaluated by logistic regression. Univariate analysis of prognostic factors (age, tumor size, FIGO stage, metastatic inguinal nodes and type of surgery) was obtained by Cox proportional hazard model. Overall survival was calculated by Kaplan-Meier curves either for the entire population and for comparison between positive and negative variables (margin status, nodes and radiotherapy) with log-rank test to determine significance. Statistical significance was reached for P < 0.05. RESULTS: Type of surgery (radical local excision vs. radical vulvectomy) and positive inguinal nodes were identified as risk factors for relapse. Positive inguinal nodes and positive margins were identified as prognostic factors either for overall survival and disease specific survival; tumor size greater than 4 cm was identified as prognostic factors for overall survival. Overall survival was 38.4% and it was significantly higher in the patients with negative margins and nodes. CONCLUSIONS: Nodes status, resection margins, age and type of surgery represent prognostic factors have to be considered for adjuvant treatment in the patients affected from vulvar carcinoma.

Bilateral giant retinal tears in Osteogenesis Imperfecta.

BACKGROUND: Osteogenesis imperfecta (OI) is a rare primarily autosomal dominant condition in which the connective tissues of bones, ligaments and sclerae do not form properly. Typically, mutations in COL1A1 and COL1A2 genes lead to the defective formation or quantity of type I collagen, the principle matrix in these tissues. Molecular genetic studies have now elucidated multiple genetic subtypes of the disorder but little literature exists on the risk of retinal tears and detachments in OI. CASE PRESENTATION: We report the first case of a child with a rare recessive type of OI, subtype VIII, resulting from a P3H1 (also known as LEPRE1) gene mutation presenting with bilateral giant retinal tears and the surgical challenges encountered in performing retinal detachment repair due to scleral thinning. The P3H1 gene encodes for prolyl 3-hydroxylase 1 which is involved in the post-translational modification of not only collagen type I but also types II and V which when mutated may result in pathological posterior vitreous detachment (PVD) and giant retinal tear detachments. CONCLUSIONS: Genetic analyses are increasingly important in such cases and may guide patient monitoring and potential prophylactic treatment, known to significantly reduce the probability of giant retinal tear detachments in other high-risk collagenopathies such as Stickler Syndrome Type I.

Impact of Recurrence of Ovarian Cancer on Quality of Life and Outlook for the Future.

OBJECTIVE: Ovarian cancer recurs in most patients, with a 5-year survival rate less than 30%. Quality of life is an increasingly important issue in patients with cancer, but there are limited data in women with recurrent ovarian cancer in this regard. MATERIALS AND METHODS: We used an ad hoc questionnaire to compare changes in health perceptions, burden of disease, and expectations for the future quality of life in women with and without recurrence of ovarian cancer. A total of 173 women were included, 116 with relapse and 57 without, undergoing follow-up in a routine clinical setting. RESULTS: Substantial differences were seen in self-assessed health status between women with and without recurrence; 33.6% and 82.4% of women with and without recurrence rated their health as good to excellent, respectively. More patients with recurrence of disease reported limitations in moderate activity than those without. Furthermore, 79.0% of women without recurrence reported that pain did not affect or only slightly affected daily activities, compared with 28.2% with recurrence. Most women with recurrence (59.5%) reported that they were able to do less than they wanted to because of their emotional status compared with only 15.8% of women without recurrence. In addition, 66.4% of women with recurrence referred that they had problems concentrating at work and home versus 26.3% of women without recurrence. CONCLUSIONS: From this survey, it is clear that relapse of disease has a negative psychological and physical impact, highlighting the importance of time without recurrence and the need for effective treatment in the long term.

Light and energy based therapeutics for genitourinary syndrome of menopause: Consensus and controversies.

Gynecologist and plastic surgeons pioneered the application of lasers in medicine and surgery almost 5 decades ago, initially used to treat cervical and vaginal pathologies. Ever since, energy-based devices have been deployed to treat pelvic pathologies and improve fertility. Recent technological developments triggered an unprecedented wave of publications, assessing the efficacy of fractional laser, and radiofrequency on the vaginal wall in reversing natural aging processes. Studies have shown that a certain degree of thermal energy deposited on the vaginal wall stimulates proliferation of the glycogen-enriched epithelium, neovascularization, and collagen formation in the lamina propria, and improves natural lubrication and control of urination. This review aimed to review such data and to guide future research. A unique assembly of experts from around the globe, compiled and edited this manuscript based on a thorough literature review and personal experience. Lasers Surg. Med. 49:137-159, 2017. © 2017 Wiley Periodicals, Inc.

Case Report: Laparoscopic Uterovaginal Anastomosis for Congenital Isolated Cervical Agenesis.

Management of cervical agenesis is a challenge owing to the complexity of the malformation and the difficulty in restoring and preserving fertility. We propose a minimally invasive fertility-sparing surgery for a 17-year-old woman with congenital cervical agenesis and a normal vagina and uterus confirmed by vaginoscopy. The patient was admitted for primary amenorrhea, hematometra, and cyclic pelvic pain. She had undergone previous laparoscopies for ovarian endometriosis. Our surgical approach involved the creation of an isthmus-vaginal anastomosis with a uterovaginal reconnection. After surgery, the patient experienced regular menstrual cycles without dysmenorrhea. At 12 months postsurgery, she continued to experience normal menstruation, and the uterovaginal connection had not stenosed. Management of congenital cervical agenesis requires accurate diagnosis that includes appropriate classification of the malformation (European Society of Human Reproduction and Embryology/European Society for Gynaecological Endoscopy classification). Surgical treatment is controversial and depends on the patient's age and desire for resolution.