Explore the vast range of titles available.

Evidence indicates that different pathways of malignant degeneration underlie the development of endometriosis-associated ovarian tumors of endometrioid and clear cell histotypes. The aim of this study was to compare data from patients affected by these two histotypes to investigate the hypothesis of a dichotomy in the histogenesis of these tumors. Clinical data and tumor characteristics of 48 patients who were diagnosed with either pure clear cell ovarian cancer and mixed endometrioid–clear cell ovarian cancer arising from endometriosis (ECC, n = 22) or endometriosis-associated endometrioid ovarian cancer (EAEOC, n = 26) were compared. A previous diagnosis of endometriosis was detected more frequently in the ECC group (32% vs. 4%, p = 0.01). The incidence of bilaterality was significantly higher in the EAOEC group (35% vs. 5%, p = 0.01) as well as a solid/cystic rate at gross pathology (57.7 ± 7.9% vs. 30.9 ± 7.5%, p = 0.02). Patients with ECC had a more advanced disease stage (41% vs. 15%; p = 0.04). A synchronous endometrial carcinoma was detected in 38% of EAEOC patients. A comparison of the International Federation of Gynecology and Obstetrics (FIGO) stage at diagnosis showed a significantly decreasing trend for ECC compared to EAEOC (p = 0.02). These findings support the hypothesis that the origin, clinical behavior and relationship with endometriosis might be different for these histotypes. ECC, unlike EAEOC, seems to develop within an endometriotic cyst, thus representing a window of possibility for ultrasound-based early diagnosis.

In countries with emerging and developing economies the need to promote development and the lack of information on the status of the Near Threatened Eurasian otter Lutra lutra have given rise for concern about the conservation status of the species. In Albania information about the distribution of this otter dates from 1985. In 2013 we resurveyed 31 sites previously surveyed in 1985, and a further 42 sites throughout the country. At each site nine habitat variables of potential importance to otters were recorded and analysed. Overall the distribution pattern in 2013 did not differ from that recorded in 1985, although a reduction in marking intensity suggested a possible decline in otter numbers. Distribution of the otter has been influenced by land use and human density, suggesting man-induced habitat changes since the fall of communism may have affected the quality and fragmentation of otter habitats.

Background: Gestational trophoblastic disease includes a rare group of benign and malignant tumors derived from abnormal trophoblastic proliferation. Malignant forms are called gestational trophoblastic neoplasia (GTN) and include invasive mole, choriocarcinoma, placental site trophoblastic tumor and epithelioid trophoblastic tumor. Standard treatment of GTN is chemotherapy. The regimen of choice mainly depends on the FIGO prognostic score. Low-risk and high-risk GTN is treated with single-agent or multiagent chemotherapy, respectively. In the case of chemoresistance, immunotherapy may represent a new therapeutic strategy. Methods: Literature obtained from searches on PubMed concerning GTN and immunotherapy was reviewed. Results: Programmed cell death 1 (PD-1) and its ligands (PD-L1/2) are expressed in GTN. Published data on PD-1/PD-L1 inhibitors alone in GTN were available for 51 patients. Pembrolizumab is an anti-PD-1 inhibitor used in chemoresistant forms of GTN. In the TROPHIMMUN trial, Avelumab, a monoclonal antibody inhibiting PD-L1, showed promising results only in patients with GTN resistant to monochemotherapy. Conversely, in patients with resistance to multiagent chemotherapy, treatment with Avelumab was discontinued due to severe toxicity and disease progression. The association of Camrelizumab and Apatinib could represent a different treatment for forms of GTN refractory to polychemotherapy or for relapses. Conclusions: Anti-PD-1 or anti-PD-L1 might represent an important new treatment strategy for the management of chemoresistant/refractory GTN.

Introduction/BackgroundRisk Reducing Salpingo-Oophorectomy (RSSO) is the main prophylactic option in BRCA-mutated patients. Current evidence indicates that the first step in the carcinogenetic process is TP53 gene mutation, resulting in tubal alterations ranging from p53 signature to serous tubal intraepithelial carcinoma (STIC), via serous tubal intraepithelial lesion (STIL), to high-grade serous ovarian carcinoma (HGSC). The aim of our study is to evaluate the role of different BRCA mutation types on the age of onset of tubal histopathological abnormalities after RRSO.MethodologyWomen with known germline pathogenic mutation to BRCA1/2 genes who underwent RRSO at San Raffaele Hospital, Milan, between November 2012 and May 2023, were considered in this analysis. Histopathological analysis was carried out by expert pathologists using standardized definitions for tubal abnormalities. Patients were assessed according to mutation type in BRCA1/2 genes: frameshift, missense, nonsense and splicing.ResultsA total of 65 patients were included, 38 (58.5%) BRCA1 and 27 (40.9%) BRCA2 mutation carriers. P53 signature was reported in 28 patients, while STIL and STIC/Cancer in 12 and 7 patients respectively. Frameshift was the most frequent mutation type in all subgroups (n=35, 52.6%). We observed an older age of onset in the group of frameshift mutation carriers with respect to non-sense mutation carriers (48.9 VS 43 years in the BRCA2-mutated p53 signature group; 62.3 VS 45.5 years in the BRCA1-mutated STIC/Ca group).ConclusionRecent evidence suggests that BRCA1/2 nonsense mutation carriers present younger age of onset of HGSC compared to frameshift mutations. Data from our study confirm this trend also for the onset of tubal abnormalities. Due to the small sample size, this finding was not statistically significant. If confirmed, on a larger scale, more personalized management for the risk-reducing strategies in BRCA1/2 women might be introduced.DisclosuresThe authors declare no conflict of interest.

Introduction/BackgroundComplete cytoreduction (macroscopic Residual Tumor, RT = 0) is an independent prognostic factor in advanced epithelial ovarian cancer (AEOC). There are currently no validated criteria for predicting complete resection at interval debulking surgery (IDS). The aim of this study is to develop a non-invasive predictive model of complete cytoreduction to IDS.MethodologyFrom January 2013 to December 2022, 108 patients underwent neoadjuvant chemotherapy (NACT) and IDS at our institution and 79 patients met all the inclusion criteria. The correlation between clinico-pathological or haematological factors and complete resection was investigated by univariate and multivariate analysis. We developed a predictive model using all statistically significant variables.ResultsAt IDS, 53 patients (67.1%) had complete cytoreduction (RT=0). Four variables were statistically correlated with residual tumor: platelet-to-lymphocyte ratio (PLR), p = 0.002; neutrophil-to-lymphocyte ratio (NLR), p = 0.041; KELIM, p = 0.002; the CA125 value after the third chemotherapy cycle, p = 0.023. Considering all 4 parameters simultaneously, we developed a ROC curve with an AUC = 0.802, a sensitivity of 35%, specificity of 98% and positive predictive value (PPV) of 90%.ConclusionOur model predicted residual tumor in a good number of patients undergoing IDS, limiting the percentage of patients with suboptimal cytoreduction. These parameters, calculated from blood samples, have low economic impact and no risk to the patient. The model should be prospectively validated in a larger series of EOC patients undergoing NACT-IDS.DisclosuresNothing to disclose.

Introduction/BackgroundScarce evidence supports Cancer Antigen 125 (CA125) as a reliable recurrence biomarker in patients affected by Ovarian Cancer (OC) on maintenance treatment with PARP inhibitors (PARPi) or Bevacizumab after response to platinum-based therapy.Our aim is to assess concordance between CA125 increase and Response Evaluation Criteria In Solid Tumours (RECIST) progression in these patients.MethodologyThe study includes 109 patients affected by CA125-sensitive OC on maintenance treatment with Bevacizumab (group A) or PARPi (group B) for at least two months after complete/partial response to platinum-based therapy. 55 patients underwent PARPi, 54 Bevacizumab. Data were concordant if CA125 increased within a month from radiological progression; otherwise they were considered discordant.Results38 (34.9%) patients relapsed under maintenance treatment; 18 (47.4%) had recurrence with PARPi, 20 (52.6%) under Bevacizumab.In group A concordant cases were 12 (60%), discordant cases accounted for 8 (40%). In this last category of patients in half cases CA125 increased before radiological progression, while in the other half marker was permanently negative; CA125 never increased after radiological progression.In group B concordant cases were 7 (38.9%), discordant ones were 11 (61.1%). In this last category of patients in 4 cases (36.4%) CA125 increased after radiological progression, while in the other 7 (63.6%) CA125 was constantly negative; marker never increased before radiological progression.ConclusionIn patients treated with PARPi CA125 does not always correlate with disease progression; in fact, in cases of relapse highlighted with imaging techniques, marker remains within the normal range. This contrasts with what happens in patients treated with Bevacizumab.In conclusion, CA125 and imaging should always be evaluated together.

Introduction/BackgroundThe presence of an immune-reactive tumor microenvironment in epithelial ovarian cancer (EOC) has boosted the development of immunotherapeutic strategy, that unfortunately have shown limited clinical efficacy. Our aim is to investigate the possible immunomodulatory effect of Olaparib and Trabectedin and whether such treatments might impact on the activity of tumor-specific T cells.MethodologyIn vitro dose finding assays for Olaparib and Trabectedin were conducted on 2 EOC cell lines and 3 patient-derived primary cultures by Incucyte® live cell imaging and flow cytometry (FC). The expression of inhibitory receptor (IR) ligands, activation molecules and tumor associated antigens (TAAs) was evaluated by FC after treatments with sub-optimal doses of each drug. The combined effect of drug treatment and T cells harbouring engineered tumor-specific T-cell receptors (TCRs) was also assessed in co-culture assays on both EOC cell lines and EOC primary cultures.ResultsAfter 24-hours treatment of EOC cells with Olaparib and Trabectedin, we found a significant modulation of some IR ligands such as PD-L1, PD-L2 and CD48 and of MHC class-I molecules. Drug treatments significantly modulated the expression of NY-ESO-1, MUC-1 and WT-1 TAAs. Furthermore, 24-hours pre-treatment with each drug before co-culture with tumor-specific TCR-edited T lymphocytes increased tumor cell death on both EOC cells and primary cultures.ConclusionOur data show that Olaparib and Trabectedin modulate the expression of immune-related molecules on EOC cells, and this effect is associated with an increased killing by tumor-specific TCR-edited T cells. Biological mechanisms at the basis of these findings deserve further investigation.DisclosuresNone

OBJECTIVESGestational trophoblastic neoplasia affects women of reproductive age and is usually treated by chemotherapy. Major concerns related to chemotherapy in young women are the possible infertility, risk of early menopause, and teratogenic effects on subsequent pregnancies. The studyʼs aim was to analyze menstrual and reproductive outcomes of women treated with single-agent versus multiagent chemotherapy for gestational trophoblastic neoplasia. METHODSOne-hundred fifty-one patients were treated. Seventy-six patients older than 45 years, with a placental site or epithelioid trophoblastic tumor, undergoing hysterectomy for patient choice, or undergoing human chorionic gonadotropin follow-up at the time of the analysis were excluded. Seventy-five patients were divided into subgroups according to International Federation of Gynecology and Obstetrics scorepatients scoring less than 7, receiving single-agent chemotherapy (group A, n = 42); patients scoring 7 or greater, receiving combination treatment (group B, n = 33). Patientsʼ outcomes were compared by univariate and multivariate analyses. RESULTSTemporary amenorrhea occurred in 33% of group A patients and 66.7% of group B (P = 0.01). Premature menopause occurred in 3 patients in group B (0% vs 9%, P = 0.02). Ten patients in group B underwent salvage hysterectomy. Pregnancy desire did not differ between the 2 groups (P = 0.555). In group A, 57.1% became pregnant; in group B, 36.4% did (P = 0.060). Instead, pregnancy rate was 52.2% among high-risk patients not undergoing hysterectomy (57.1% vs 52.2%, P = 0.449). There was no difference in miscarriage (P = 0.479) and premature birth (P = 0.615) rates. In a multivariate analysis that included age, International Federation of Gynecology and Obstetrics score, chemotherapy type, use of assisted reproductive technologies, previous pregnancies, and pregnancy desire, only age (P = 0.006) and pregnancy desire (P = 0.002) had a significant impact on the probability to have subsequent pregnancies. CONCLUSIONSExcept for the risk of premature ovarian failure, a rare adverse effect of combined treatments, both single-agent and multiagent chemotherapy can be safely administered to patients with a desire for childbearing. High-risk patients have worse reproductive outcomes because they undergo hysterectomy more frequently than low-risk patients.

ObjectiveUltrasound features of granulosa cell tumors of the ovary are still poorly defined. The aim of this study is to widen current knowledge on the role of sonographic gray scale and pattern recognition in the characterization of these tumors and to compare the ultrasound characteristics of primary diagnosis and recurrences.MethodsTransvaginal ultrasound images of primary diagnosis or recurrences of histologically-confirmed granulosa cell tumors of the ovary were retrospectively retrieved from a dedicated database designed for the collection of clinical and ultrasound data from January 2001 to January 2019. All patients included were treated at San Raffaele and Santa Chiara Hospitals. Women with a concomitant diagnosis of another malignancy other than endometrial carcinoma were excluded from the study. All ultrasound images were described according to International Ovarian Tumor Analysis terminology and examined by experienced ultrasound examiners.ResultsA total of 27 patients were included: 24 with adult and 3 with juvenile ovarian granulosa cell tumors. At primary diagnosis, mean ovarian mass size was 103.8 mm (range 30–200). On ultrasound evaluation at primary diagnosis, 12 patients presented with a multilocular solid lesion (48%), 9 with a solid lesion (36%), and 4 with a multilocular lesion(16%). The echogenicity of the cyst was low level or anechoic, mixed, or hemorrhagic in 56.3%, 31.2%, and 12.5% of cases, respectively. Most tumors (45.1%), including first diagnosis and relapses, had a moderate to high color score on doppler evaluation.ConclusionsOur study showed that sonographic features and pattern recognition of relapses were comparable to those of tumors at primary diagnosis. In order to highlight the importance of transvaginal ultrasound evaluation during follow-up, further studies based on a standardized ultrasound characterization of ovarian masses are recommended.

ObjectiveWomen older than 40 years develop gestational trophoblastic neoplasia (GTN) after a hydatidiform mole (HM) more often than do younger women. Therefore, in elderly women, primary hysterectomy has been advocated as first-line treatment. The aim of the present study was to evaluate whether hysterectomy could reduce the incidence of GTN after a diagnosis of HM.MethodsSeventy-six of 442 patients referred to our unit for an HM between 1994 and 2015 were older than 40 years old. Among these, 12 patients were treated by primary hysterectomy. We compared clinical features, serum human chorionic gonadotrophin (hCG), incidence of GTN, and further treatments in these patients and in those who underwent evacuation and serum hCG monitoring, using univariate and multivariate analyses.ResultsPatients treated by primary hysterectomy all had a diagnosis of a complete or invasive HM, had more hyperemesis than did control subjects (82% vs 37%, P = 0.008), and had an increased uterine volume (100% vs 41%, P = 0.001). Seven of them developed a subsequent GTN, whereas 5 patients achieved complete remission of disease after surgery (58% vs 30%, P = 0.094). All the patients who developed a GTN after surgery showed lower hCG levels than did control subjects (mean, 671.4 [SD, 1178.4] IU/L vs 23,919.4 [SD, 34,284.9] IU/L; P = 0.005), but there were no significant differences in the amount and type of chemotherapy needed to achieve remission.ConclusionsPrimary hysterectomy after 40 years old in women affected by HM does not reduce the incidence of GTN and amount of chemotherapy. Although further studies are needed to confirm these results, a careful hCG monitoring should be recommended in these high-risk patients.