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STUDY QUESTION How should fertility-sparing treatment of patients with endometrial carcinoma be performed? SUMMARY ANSWER Forty-eight recommendations were formulated on fertility-sparing treatment of patients with endometrial carcinoma. WHAT IS KNOWN ALREADY The standard surgical treatment of endometrial carcinoma consisting of total hysterectomy with bilateral salpingo-oophorectomy drastically affects the quality of life of patients and creates a challenge for clinicians. Recent evidence-based guidelines of the European Society of Gynaecological Oncology (ESGO), the European SocieTy for Radiotherapy & Oncology (ESTRO) and the European Society of Pathology (ESP) provide comprehensive guidelines on all relevant issues of diagnosis and treatment in endometrial carcinoma in a multidisciplinary setting. While addressing also work-up for fertility preservation treatments and the management and follow-up for fertility preservation, it was considered relevant to further extend the guidance on fertility-sparing treatment. STUDY DESIGN, SIZE, DURATION A collaboration was set up between the ESGO, the European Society of Human Reproduction and Embryology (ESHRE) and the European Society for Gynaecological Endoscopy (ESGE), aiming to develop clinically relevant and evidence-based guidelines focusing on key aspects of fertility-sparing treatment in order to improve the quality of care for women with endometrial carcinoma across Europe and worldwide. PARTICIPANTS/MATERIALS, SETTING, METHODS ESGO/ESHRE/ESGE nominated an international multidisciplinary development group consisting of practising clinicians and researchers who have demonstrated leadership and expertise in the care and research of endometrial carcinoma (11 experts across Europe). To ensure that the guidelines are evidence-based, the literature published since 2016, identified from a systematic search was reviewed and critically appraised. In the absence of any clear scientific evidence, judgement was based on the professional experience and consensus of the development group. The guidelines are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines were reviewed by 95 independent international practitioners in cancer care delivery and patient representatives. MAIN RESULTS AND THE ROLE OF CHANCE The multidisciplinary development group formulated 48 recommendations in four sections; patient selection, tumour clinicopathological characteristics, treatment and special issues. LIMITATIONS, REASONS FOR CAUTION Of the 48 recommendations, none could be based on level I evidence and only 16 could be based on level II evidence, implicating that 66% of the recommendations are supported only by observational data, professional experience and consensus of the development group. WIDER IMPLICATIONS OF THE FINDINGS These recommendations provide guidance to professionals caring for women with endometrial carcinoma, including but not limited to professionals in the field of gynaecological oncology, onco-fertility, reproductive surgery, endoscopy, conservative surgery and histopathology, and will help towards a holistic and multidisciplinary approach for this challenging clinical scenario. STUDY FUNDING/COMPETING INTEREST(S) All costs relating to the development process were covered from ESGO, ESHRE and ESGE funds. There was no external funding of the development process or manuscript production. G.S. has reported grants from MSD Italia S.r.l., advisory boards for Storz, Bayer, Astrazeneca, Metronic, TESARO Bio Italy S.r.l and Johnson & Johnson, and honoraria for lectures from Clovis Oncology Italy S.r.l. M.G. has reported advisory boards for Gedeon Richter and Merck. The other authors have reported no conflicts of interest. DISCLAIMER This document represents the views of ESHRE, ESGO and ESGE which are the result of consensus between the relevant stakeholders and where relevant based on the scientific evidence available at the time of preparation. The recommendations should be used for informational and educational purposes. They should not be interpreted as setting a standard of care, or be deemed inclusive of all proper methods of care nor exclusive of other methods of care reasonably directed to obtaining the same results. They do not replace the need for application of clinical judgement to each individual presentation, nor variations based on locality and facility type.

ObjectiveWhile human papillomavirus (HPV) has been shown to play a significant role in cervical cancer carcinogenesis (HPV associated cases), a considerable percentage of cervical cancers occur independently of HPV status (HPV independent).MethodsIn this retrospective study of 254 locally advanced cervical cancer patients treated with chemoradiotherapy and radical surgery, HPV genotypes were determined using the Anyplex II HPV28 kit that uses multiplex, real time polymerase chain reaction technology. The primary endpoints of this study were to evaluate the complete response to chemoradiotherapy (pathologic complete response), the presence of microscopic (<3 mm, pathologic micro partial response, group 1) and macroscopic (>3 mm, pathologic macro partial response, group 2) residual carcinoma in the cervix, and the persistence of metastatic lymph nodes (group 3) in HPV independent cervical cancers. Secondary endpoints were evaluation of disease-free survival and overall survival.ResultsOf 254 patients studied, 21 cases (8.3%) of cervical cancer were determined to be HPV independent. The percentage of pathologic complete response was found to be higher in the HPV associated group compared with the HPV independent group (pConclusionsThis study showed that HPV status at diagnosis could be a relevant factor for clinical outcomes in locally advanced cervical cancer patients.

Endometrial carcinosarcoma is a rare and aggressive high-grade endometrial carcinoma with secondary sarcomatous trans-differentiation (conversion theory). The clinical presentation and diagnostic work-up roughly align with those of the more common endometrioid counterpart, although endometrial carcinosarcoma is more frequently diagnosed at an advanced stage. Endometrial carcinosarcoma is not a single entity but encompasses different histological subtypes, depending on the type of carcinomatous and sarcomatous elements. The majority of endometrial carcinosarcomas are characterized by p53 abnormalities. The proportion ofPOLEand microsatellite instablity-high (MSI-H) is directly related to the epithelial component, being approximately 25% and 3% in endometrioid and non-endometrioid components.The management of non-metastatic disease is based on a multimodal approach with optimal surgery followed by (concomitant or sequential) chemotherapy and radiotherapy, even for early stages. Palliative chemotherapy is recommended in the metastatic or recurrent setting, with carboplatin/paclitaxel doublet being the first-line regimen. Although the introduction of immunotherapy plus/minus a tyrosine kinase inhibitor shifted the paradigm of treatment of patients with recurrent endometrial cancer, patients with endometrial carcinosarcoma were excluded from most studies evaluating single-agent immunotherapy or the combination. However, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) approved the use of pembrolizumab and lenvatinib in endometrial cancer (all histotypes) after progression on chemotherapy and single-agent immunotherapy in MSI-H cancers. In the era of precision medicine, emerging knowledge on molecular endometrial carcinosarcoma is opening new promising therapeutic options for more personalized treatment. The present review outlines state-of-the-art knowledge and future directions for patients with endometrial carcinosarcoma.

OBJECTIVE: To describe the clinical and ultrasound characteristics of three types of rare malignant ovarian germ cell tumor: embryonal carcinoma, non-gestational choriocarcinoma and malignant mixed germ cell tumor. METHODS: This was a retrospective multicenter study. From the International Ovarian Tumor Analysis (IOTA) database, we identified patients with a histological diagnosis of ovarian embryonal carcinoma, non-gestational choriocarcinoma or malignant mixed germ cell tumor, who had undergone preoperative ultrasound examination by an experienced ultrasound examiner between 2000 and 2020. Additional patients with the same histology were identified from the databases of the departments of gynecological oncology in the participating centers. All tumors were described using IOTA terminology. Three examiners reviewed all available ultrasound images and described them using pattern recognition. RESULTS: One patient with embryonal carcinoma, five patients with non-gestational ovarian choriocarcinoma and seven patients with ovarian malignant mixed germ cell tumor (six primary tumors and one recurrence) were identified. Seven patients were included in the IOTA studies and six patients were examined outside of the IOTA studies. The median age at diagnosis was 26 (range, 14-77) years. Beta-human chorionic gonadotropin levels were highest in non-gestational choriocarcinomas and alpha-fetoprotein levels were highest in malignant mixed germ cell tumors. Most tumors were International Federation of Gynecology and Obstetrics (FIGO) Stage I (9/12 (75.0%)). All tumors were unilateral, and the median largest diameter was 129 (range, 38-216) mm. Of the tumors, 11/13 (84.6%) were solid and 2/13 (15.4%) were multilocular-solid; 9/13 (69.2%) manifested abundant vascularization on color Doppler examination. Using pattern recognition, the typical ultrasound appearance was a large solid tumor with inhomogeneous echogenicity of the solid tissue and often dispersed cysts which, in most cases, were small and irregular. Some tumors had smooth contours while others had irregular contours. CONCLUSIONS: A unilateral, large solid tumor with inhomogeneous echogenicity of the solid tissue and with dispersed small cystic areas in a young woman should raise the suspicion of a rare malignant germ cell tumor. This suspicion can guide the clinician to test tumor markers specific for malignant germ cell tumors. © 2020 International Society of Ultrasound in Obstetrics and Gynecology. ispartof: ULTRASOUND IN OBSTETRICS & GYNECOLOGY vol:57 issue:6 pages:987-994 ispartof: location:England status: published

Uterine tumor resembling ovarian sex-cord tumor (UTROSCT) is a rare distinct cancer included in the current World Health Organization classification of endometrial stromal tumors. A battery of immunohistochemical markers are necessary for accurate diagnosis. Although few case reports and case series have been documented and therefore providing robust prognostic information several authors agree to consider UTROSCT as a low malignant potential tumour. In literature only five cases of conservative management were reported. We reported our experience and a review of conservative cases of literature. In this article we describe a series of 10 cases of UTROSCT and their clinical and pathologic feature. We report two cases of conservative surgical approach obtaining a successfully pregnancies. All of the patients are still alive. In conclusion, fertility sparing surgery should be offered to patients who wish preserve their fertility however radical surgery must be considerate after childbirth. Close follow-up is required for all patients due to the lack of prognostic biomarkers and long follow up is needed to evaluate safety of conservative surgery.

Objective To characterize T lymphocyte infiltration and programmed cell death protein-1 (PD-1)/programmed death-ligand 1 (PD-L1) expression in early-stage endometriosis-associated ovarian cancer (EAOC), ovarian endometriosis (OE), atypical endometriosis (AE), and deep endometriosis (DE). Design Case-control, retrospective study. Setting Research University Hospital. Patient(s) A total of 362 patients with a histologic diagnosis of EAOC, OE, AE, or DE were identified between 2000 and 2019 from Fondazione Policlinico Universitario Agostino Gemelli IRCCS and Gemelli Molise SpA tissue data banks. A 1:1 propensity score-matched method yielded matched pairs of 55 subjects with EAOC, 55 patients with OE, 12 patients with AE, and 42 patients with DE, resulting in no differences in family history of cancer, parity, and use of oral contraceptives. Intervention(s) Immunohistochemistry assays using the following primary antibodies: CD3+; CD4+; CD8+; PD-1; and PD-L1. Main Outcome Measure(s) To characterize T lymphocyte infiltration and PD-1/PD-L1 expression in 4 different endometriosis-related diseases. Result(s) Endometriosis-associated ovarian cancer cases displayed significantly higher levels of PD-1/PD-L1 expression compared with all other endometriosis-related diseases (vs. OE vs. AE vs. DE). Moreover, a significantly lower count of infiltrating T lymphocytes was observed in EAOC cases compared with OE ones. Finally, one-third of OE cases showed a cancer-like PD-1/PD-L1 expression profile. Conclusion(s) Endometriosis-associated ovarian cancer is characterized by higher levels of PD-1/PD-L1 expression compared with benign endometriosis-related diseases. This profile was found in one-third of clinically benign cases, suggesting that it develops early in the carcinogenesis process.

Background The aim of this study was to assess the agreement rate between intraoperative evaluation (IOE) and final diagnosis (FD) in a series of surgically resected endometrial carcinoma (EC), with a preoperative ambiguous or inconclusive diagnosis by endometrial biopsies and imaging. Methods A retrospective study was performed selecting patients who underwent surgery with IOE for suspected EC at our institution from 2012 to 2018. A K coefficient was determined with respect to the histotype, tumor grade, myometrial infiltration and cervical involvement. Results Data analysis has been performed on 202 women. The IOE evaluation was distributed as Endometrioid (n = 180) and Non-Endometrioid (n = 22). The comparison between the frozen section (FS) and the definitive histological subtype showed an overall agreement rate of 93,07% (k = 0.612) and an agreement of 97.2% for Endometrioid vs 59% for Non-Endometrioid tumors. The FIGO system grading was the same in 91,1% of patients, none was upgraded and in 8,9% downgraded. Observed agreements were 89,11% and 95,54% for myometrial and cervical involvement, respectively. Conclusions The good agreement between intraoperative grading, myometrial invasion and their histological definition on permanent sections highlights that FS is a good predictor for surgical outcome, in particular in presence of a preoperative ambiguous or inconclusive diagnostic evaluation.

BRCA 1/2 genes mutation status can already determine the therapeutic algorithm of high grade serous ovarian cancer patients. Nevertheless, its assessment is not sufficient to identify all patients with genomic instability, since BRCA 1/2 mutations are only the most well-known mechanisms of homologous recombination deficiency (HR-d) pathway, and patients displaying HR-d behave similarly to BRCA mutated patients. HRd assessment can be challenging and is progressively overcoming BRCA testing not only for prognostic information but more importantly for drugs prescriptions. However, HR testing is not already integrated in clinical practice, it is quite expensive and it is not refundable in many countries. Selecting patients who are more likely to benefit from this assessment (BRCA 1/2 WT patients) at an early stage of the diagnostic process, would allow an optimization of genomic profiling resources. In this study, we sought to explore whether somatic BRCA1/2 genes status can be predicted using computational pathology from standard hematoxylin and eosin histology. In detail, we adopted a publicly available, deep-learning-based weakly supervised method that uses attention-based learning to automatically identify sub regions of high diagnostic value to accurately classify the whole slide (CLAM). The same model was also tested for progression free survival (PFS) prediction. The model was tested on a cohort of 664 (training set: n = 464, testing set: n = 132) ovarian cancer patients, of whom 233 (35.1%) had a somatic BRCA 1/2 mutation. An area under the curve of 0.7 and 0.55 was achieved in the training and testing set respectively. The model was then further refined by manually identifying areas of interest in half of the cases. 198 images were used for training (126/72) and 87 images for validation (55/32). The model reached a zero classification error on the training set, but the performance was 0.59 in terms of validation ROC AUC, with a 0.57 validation accuracy. Finally, when applied to predict PFS, the model achieved an AUC of 0.71, with a negative predictive value of 0.69, and a positive predictive value of 0.75. Based on these analyses, we have planned further steps of development such as proving a reference classification performance, exploring the hyperparameters space for training optimization, eventually tweaking the learning algorithms and the neural networks architecture for better suiting this specific task. These actions may allow the model to improve performances for all the considered outcomes.

OBJECTIVES Fusion imaging is an emerging technique that combines real-time ultrasound examination with images acquired previously using other modalities, such as computed tomography (CT), magnetic resonance imaging and positron emission tomography. The primary aim of this study was to evaluate the feasibility of fusion imaging in patients with suspicion of ovarian or peritoneal cancer. Secondary aims were: to compare the agreement of findings on fusion imaging, CT alone and ultrasound imaging alone with laparoscopic findings, in the assessment of extent of intra-abdominal disease; and to evaluate the time required for the fusion imaging technique. METHODS Patients with clinical and/or radiographic suspicion of advanced ovarian or peritoneal cancer who were candidates for surgery were enrolled prospectively between December 2019 and September 2020. All patients underwent a CT scan and ultrasound and fusion imaging to evaluate the presence or absence of the following abdominal-cancer features according to the laparoscopy-based scoring model (predictive index value (PIV)): supracolic omental disease, visceral carcinomatosis on the liver, lesser omental carcinomatosis and/or visceral carcinomatosis on the lesser curvature of the stomach and/or spleen, involvement of the paracolic gutter(s) and/or anterior abdominal wall, involvement of the diaphragm and visceral carcinomatosis on the small and/or large bowel (regardless of rectosigmoid involvement). The feasibility of the fusion examination in these patients was evaluated. Agreement of each imaging method (ultrasound, CT and fusion imaging) with laparoscopy (considered as reference standard) was calculated using Cohen's kappa coefficient. RESULTS Fifty-two patients were enrolled into the study. Fusion imaging was feasible in 51 (98%) of these patients (in one patient, it was not possible for technical reasons). Two patients were excluded because laparoscopy was not performed, leaving 49 women in the final analysis. Kappa values for CT, ultrasound and fusion imaging, using laparoscopy as the reference standard, in assessing the PIV parameters were, respectively: 0.781, 0.845 and 0.896 for the great omentum; 0.329, 0.608 and 0.847 for the liver surface; 0.472, 0.549 and 0.756 for the lesser omentum and/or stomach and/or spleen; 0.385, 0.588 and 0.795 for the paracolic gutter(s) and/or anterior abdominal wall; 0.385, 0.497 and 0.657 for the diaphragm; and 0.336, 0.410 and 0.469 for the bowel. The median time needed to perform the fusion examination was 20 (range, 10-40) min. CONCLUSION Fusion of CT images and real-time ultrasound imaging is feasible in patients with suspicion of ovarian or peritoneal cancer and improves the agreement with surgical findings when compared with ultrasound or CT scan alone. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Objectives Lymph-vascular space invasion (LVSI) is associated with an increased risk of recurrence. Usually, the interpretation of LVSI is just qualitative, as presence or absence. The aim of this study is to examine the quantitative analysis of LVSI. Methods Retrospective multicentre study. It included 2300 consecutive patients who received a histologically confirmed diagnosis of endometrial cancer between January 2000 and December 2018 at the Gynaecologic Oncology Unit of two tertiary hospitals in Italy. Results The rate of lymph node metastasis increased from the 5% in patients with no LVSI, to 15% in patients with focal LVSI and 33% in those with diffuse LVSI (p Conclusion The presence of diffuse LVSI is an independent risk factor of both lymph node metastasis and distant recurrence in endometrial cancer patients. It is associated with decreased OS and DFS. Adjuvant radiation improved survival regardless of grading, histotype, and lymph nodal metastasis in women with diffuse LVSI.

Introduction Tumor-free distance (TFD), defined as the minimum distance of uninvolved stroma between the tumor and peri-cervical stromal ring, was recently proposed as predictive marker of recurrence in patients with early-stage cervical cancer treated by primary surgery (particularly if ≤3.5 mm). The aims of the present study were to assess the prognostic value of TFD and to compare TFD with other known prognostic markers in early-stage cervical cancer. Methods Patients with pathologic FIGO 2009 stage IA1-IIB cervical cancer, treated by primary radical surgical treatment between 01/2000 and 12/2018, were retrospectively included. Adjuvant treatment was administered according to the presence of previously established pathologic risk factors. TFD was measured histologically on the hysterectomy specimen. Results 368 patients were included in the study. 115 (31.2%) patients had TFD≤3.5 mm and 253 (68.8%) had TFD>3.5 mm. TFD≤3.5 mm was associated with worse 5-year disease-free survival (DFS) and overall survival (OS), compared with TFD>3.5 mm (p=0.028 and p=0.041, respectively) (figure 1). DFS and OS differences were more evident in subgroups of patients who did not receive adjuvant treatment (DFS, p=0.001 and OS, p=0.001) and who underwent laparotomy approach (DFS, p=0.017 and OS, p=0.034). TFD≤3.5 mm represented the strongest predictor for lymph node metastasis and pathologic parametrial involvement at both univariate and multivariate analysis (table 1). Conclusions TFD≤3.5 mm represents a poor prognostic factor significantly associated with lymph node metastasis and pathologic parametrial infiltration. The possibility to obtain this parameter by radiological imaging makes it the easiest measurable pre-operative marker to predict the presence of high-risk pathologic factors.

OBJECTIVE: To describe the clinical and sonographic characteristics of malignant ovarian yolk sac tumors (YSTs). METHODS: In this retrospective multicenter study, we included 21 patients with a histological diagnosis of ovarian YST and available transvaginal ultrasound images and/or videoclips and/or a detailed ultrasound report. Ten patients identified from the International Ovarian Tumor Analysis (IOTA) studies had undergone a standardized preoperative ultrasound examination, by an experienced ultrasound examiner, between 1999 and 2016. A further 11 patients were identified through medical files, for whom ultrasound images were retrieved from local image workstations and picture archiving and communication systems. All tumors were described using IOTA terminology. The collected ultrasound images and videoclips were used by two observers for additional characterization of the tumors. RESULTS: All cases were pure YSTs, except for one that was a mixed tumor (80% YST and 20% embryonal carcinoma). Median age at diagnosis was 25 (interquartile range (IQR), 19.5-30.5) years. Seventy-six percent (16/21) of women had an International Federation of Gynecology and Obstetrics (FIGO) Stage I-II tumor at diagnosis. Fifty-eight percent (11/19) of women felt pain during the ultrasound examination and one presented with ovarian torsion. Median serum α-fetoprotein (S-AFP) level was 4755 (IQR, 1071-25 303) µg/L and median serum CA 125 level was 126 (IQR, 35-227) kU/L. On ultrasound assessment, 95% (20/21) of tumors were unilateral. The median maximum tumor diameter was 157 (IQR, 107-181) mm and the largest solid component was 110 (IQR, 66-159) mm. Tumors were classified as either multilocular-solid (10/21; 48%) or solid (11/21; 52%). Papillary projections were found in 10% (2/21) of cases. Most (20/21; 95%) tumors were well vascularized (color score, 3-4) and none had acoustic shadowing. Malignancy was suspected in all cases, except in the patient with ovarian torsion, who presented a tumor with a color score of 1, which was classified as probably benign. Image and videoclip quality was considered as adequate in 18/21 cases. On review of the images and videoclips, we found that all tumors contained both solid components and cystic spaces, and that 89% (16/18) had irregular, still fine-textured and slightly hyperechoic solid tissue, giving them a characteristic appearance. CONCLUSION: Malignant ovarian YSTs are often detected at an early stage, in young women usually in the second or third decade of life, presenting with pain and markedly elevated S-AFP. On ultrasound, malignant ovarian YSTs are mostly unilateral, large and multilocular-solid or solid, with fine-textured slightly hyperechoic solid tissue and rich vascularization. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.. ispartof: ULTRASOUND IN OBSTETRICS & GYNECOLOGY vol:56 issue:2 pages:276-284 ispartof: location:England status: published

Objectives: The interpretation of lymph-vascular space invasion (LVSI) is usually qualitative, as presence or absence. The aim of this study is to investigate the prognostic role of LVSI in patients affected by endometrial cancer, when evaluated with a semiquantitative analysis. Methods: This retrospective multicentre study enrolled patients who received a histologically confirmed diagnosis of endometrial cancer. The assessment of LVSI was semiquantitative in accordance with the three-tiered scoring system (absent, focal and diffuse). Results: Among 1258 patients with surgical-stage endometrial cancer, LVSI has been found in 32.8% of cases (n = 412), whose 12.7% (n = 160) were focal, and 20% (n = 252) diffuse. The rate of lymph node metastasis increased from the 5% in patients with no LVSI to 15% in patients with focal LVSI and 33% in those with diffuse LVSI (p < 0.001). Distant recurrences were more frequent in patients with diffuse LVSI than in focal or no LVSI (24.9% versus 14.7% and 6.6%, respectively, p < 0.001). Diffuse LVSI was found to significantly increase the risk of distant metastasis (adjusted odds ratio (A OR) 2.57, p < 0.001). Adjuvant radiation were associated with improved overall survival (OS) and disease-free survival (DFS) in patients with diffuse LVSI. Conclusion: The presence of diffuse LVSI is an independent risk factor for both lymph node metastasis and distant recurrence in endometrial cancer patients, and it is associated with a significantly decreased OS and DFS. Adjuvant radiation improved survival regardless of grading, histotype and lymph nodal metastasis in women with diffuse LVSI.

Objective In 5-30% of cases, endometrial cancer occurs in women age 45 or younger. A valid option for women desiring fertility is primary hormonal treatment, such as oral megestrol acetate (MA) alone or combined with hysteroscopic resection1, or levonorgestrel-releasing intrauterine system (LNG-IUS); however, 20-30% and 41% patients undergoing progestin-based treatments alone failed to achieve complete response (CR) and recur2. The current knowledge is drawn from observational cohort studies on small series of patients for which long follow-up is rare3. Moreover, the worldwide data on hysteroscopic treatment are still limited4. Here, we evaluated the prognostic outcome of a large, single-institution series of young women diagnosed with endometrial atypical hyperplasia (EAH)/endometrioid intraepithelial neoplasia (EIN) and early stage endometrial cancer (EEC) who were selected for fertility preservation and treated with oral MA combined with hysteroscopic resection in the subgroup of patients carrying a single lesion. Study Design Patients with EAH/EIN (n= 49) or well differentiated EEC (n= 36), FIGO stage IA (no myometrial invasion at MRI) were prospectively included from June 2007 to December 2019. The inclusion criteria for conservative treatment followed NCCN guidelines 20185. All patients received MA 160 mg daily for a minimum of 6 months and were evaluated by hysteroscopy-guided biopsy and ultrasounds every three months until achieving CR. Next, follow-up was performed every 3 months until pregnancy was obtained. Only suspected single lesion (cancerous polyp or neoformation) were hysteroscopically removed before progestin treatment with the NEMos (Neoplasia Endometrium Myometrium organized sections) technique1,6. Multifocal lesions were treated with MA alone. Results The median follow-up time was 36 months (range 6-150). A total of 82 patients (96.5%) achieved CR. The mean treatment duration for achieving CR was 4.51 months (range 3-18 months). Hysteroscopic removal of EAH/EIN or EEC prior to therapy was the only factor significantly associated with shorter treatment duration to achieve CR (p=0.001). Patients who underwent hysteroscopic resection plus MA (n=15) or MA therapy alone (n=67) achieved CR in 3.4 months (range 3-18) and 4.75 months (range 3-18), respectively. The cumulative relapse rate was 62% (51/82) and the median time to relapse was 21 months (28 months for EAH/EIN and 21 months for EEC). Patients with lesion removed by hysteroscopy plus MA relapsed later (average 38, median 33, range 6-150 months) compared to patients who were treated with MA alone (average 27, median 18, range 6-108 months) (p=0.043) (Fig. 1). Among the 82 patients who achieved CR, 52 patients planned for parenthood; and 26 patients (50%) achieved at least one pregnancy. Only 4 patients received in vitro fertilization. Spontaneous miscarriage rate was 17% (9 out of 52 cases) and live birth rate was 32.7% (17 out of 52 cases), respectively. Conclusion In this study, we report our institutional experience with a large series of EAH/EIN (n=49) and EEC (n=36) patients eligible for fertility-sparing treatment with MA alone or combined with NEMo’s hysteroscopic resection1,5. We found that hysteroscopic resection of EAH/EIN or EEC in combination with oral progestin therapy was significantly associated with shorter treatment duration to achieve CR and longer time to relapse, compared to patients treated with progestin therapy alone. This large, single-institution study provides convincing data on the efficacy of MA plus hysteroscopic resection in conservative treatment of both EAH/EIN and EC patients, which will have to be confirmed in a prospective multi-institutional trial.

Objective Coronavirus disease 2019 (COVID-19) has caused rapid and drastic changes in cancer management. The Italian Society of Gynecology and Obstetrics (SIGO), and the Multicenter Italian Trials in Ovarian cancer and gynecologic malignancies (MITO) promoted a national survey aiming to evaluate the impact of COVID-19 on clinical activity of gynecologist oncologists and to assess the implementation of containment measures against COVID-19 diffusion. Methods The survey consisted of a self-administered, anonymous, online questionnaire. The survey was sent via email to all the members of the SIGO, and MITO groups on April 7, 2020, and was closed on April 20, 2020. Results Overall, 604 participants completed the questionnaire with a response-rate of 70%. The results of this survey suggest that gynecologic oncology units had set a proactive approach to COVID-19 outbreak. Triage methods were adopted in order to minimize in-hospital diffusion of COVID-19. Only 38% of gynecologic surgeons were concerned about COVID-19 outbreak. Although 73% of the participants stated that COVID-19 has not significantly modified their everyday practice, 21% declared a decrease of the use of laparoscopy in favor of open surgery (19%). However, less than 50% of surgeons adopted specific protection against COVID-19. Additionally, responders suggested to delay cancer treatment (10%-15%), and to perform less radical surgical procedures (20%-25%) during COVID-19 pandemic. Conclusions National guidelines should be implemented to further promote the safety of patients and health care providers. International cooperation is of paramount importance, as heavily affected nations can serve as an example to find out ways to safely preserve clinical activity during the COVID-19 outbreak.

Surgical pathology units face chemical and biological risks. While chemical risks have been intensely evaluated since the formalin ban, less attention has been drown to biological risks. The actual epidemiologic situation due to the SARS-CoV-2 pandemia has raised a series of questions, which need to be addressed as soon as possible. We have to pursue two lines of action: on one side we must immediately adopt urgent measures to reduce the risk of SARS-CoV-2 infection of our laboratory personnel, and on the other side we must address crucial technical and organizational aspects of biological risk reduction, preserving as much as possible the quality of tissue and cell samples. Continue reading (Download PDF)

OBJECTIVE: To describe the clinical and ultrasound characteristics of ovarian pure clear cell carcinoma. METHODS: This was a retrospective study involving data from 11 ultrasound centers. From the International Ovarian Tumor Analysis (IOTA) database, 105 patients who had undergone preoperative ultrasound examination by an experienced ultrasound examiner between 1999 and 2016 were identified with a histologically confirmed pure clear cell carcinoma of the ovary. An additional 47 patients diagnosed with pure clear cell carcinoma between 1999 and 2016 and with available complete preoperative ultrasound reports were identified retrospectively from the databases of the departments of gynecological oncology in the participating centers. The ultrasound images of all tumors were described using IOTA terminology. Clinical and ultrasound characteristics were analyzed for the whole group, and separately, for patients with and those without histologically confirmed endometriosis, and for patients with evidence of tumor developing from endometriosis. RESULTS: Median age of the 152 patients was 53.5 (range, 28-92) years and 92/152 (60.5%) tumors were FIGO Stage I. Most tumors (128/152, 84.2%) were unilateral. On ultrasound examination, all tumors contained solid components and 36/152 (23.7%) were completely solid masses. The median largest diameter of the lesion was 117 (range, 25-310) mm. Papillary projections were present in 58/152 (38.2%) masses and, in most of these (51/56, 91.1%), vascularized papillary projections were seen. Information regarding the presence, site and type of pelvic endometriosis at histology was available for 130/152 patients. Endometriosis was noted in 54 (41.5%) of these. In 24/130 (18.6%) patients, the tumor was judged to have developed from endometriosis. Patients with, compared to those without, evidence of tumor developing from endometriosis were younger (median 47.5 vs 55.0 years, respectively), and ground-glass echogenicity of cyst fluid was more common in pure clear cell cancers developing from endometriosis (10/20 vs 13/79 (50.0% vs 16.5%), respectively). CONCLUSIONS: Ovarian pure clear cell carcinoma is usually diagnosed at an early stage and typically appears as a large unilateral mass with solid components. Patients with clear cell carcinoma developing from endometriosis are younger than other patients with clear cell carcinoma, and clear cell cancers developing from endometriosis more often manifest ground-glass echogenicity of cyst fluid. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd. ispartof: Ultrasound In Obstetrics & Gynecology vol:52 issue:6 pages:792-800 ispartof: location:England status: published

To assess the diagnostic performance of conventional and DW-MRI parameters in the detection of residual tumor in locally advanced cervical cancer (LACC) patients treated with neoadjuvant chemoradiotherapy (nCRT) and radical surgery Between October 2010 and June 2014, 88 patients with histologically documented cervical cancer (FIGO stage IB2–IVA) were prospectively included in the study. Maximum tumor diameters (maxTD), tumor volume (TV), DWI signal intensity (SI), and ADCmean were evaluated at MRI after nCRT. Histology was the reference standard. Treatment response was classified as complete (CR) or partial (PR). Comparisons were made with Mann-Whitney, χ2, and Fisher’s exact tests. ROC curves were generated for variables to evaluate diagnostic ability to predict PR and to determine the best cutoff value to predict PR. For each diagnostic test, sensitivity, specificity, and accuracy were calculated. TV and maxTD were significantly smaller in the CR than in the PR group (p

OBJECTIVE: To describe the clinical and ultrasound characteristics of ovarian pure endometrioid carcinomas.METHODS: This was a retrospective multicenter study of patients with a histological diagnosis of pure endometrioid carcinoma. We identified 161 patients from the International Ovarian Tumor Analysis (IOTA) database who had undergone preoperative ultrasound examination by an experienced ultrasound examiner between 1999 and 2016, and another 78 patients from the databases of the departments of gynecological oncology in the participating centers. All tumors were described using IOTA terminology. In addition, one author reviewed all available ultrasound images and described them using pattern recognition.RESULTS: Median age of the 239 patients was 55 years (range, 19-88 years). On ultrasound examination, two (0.8%) endometrioid carcinomas were described as unilocular cysts, three (1.3%) as multilocular cysts, 37 (15.5%) as unilocular-solid cysts, 115 (48.1%) as multilocular-solid cysts and 82 (34.3%) as solid masses. Median largest tumor diameter was 102.5 mm (range, 20-300 mm) and median largest diameter of the largest solid component was 63 mm (range, 9-300 mm). Papillary projections were present in 70 (29.3%) masses. Most cancers (188 (78.7%)) were unilateral. In 49 (20.5%) cases, the cancer was judged by the pathologist to develop from endometriosis. These cancers, compared with those without evidence of tumor developing from endometriosis, more often manifested papillary projections on ultrasound (46.9% (23/49) vs 24.7% (47/190)), were less often bilateral (8.2% (4/49) vs 24.7% (47/190)) and less often associated with ascites (6.1% (3/49) vs 28.4% (54/190)) and fluid in the pouch of Douglas (24.5% (12/49) vs 48.9% (93/190)). Retrospective analysis of available ultrasound images using pattern recognition revealed that many tumors without evidence of tumor developing from endometriosis (36.3% (41/113)) had a large central solid component entrapped within locules, giving the tumor a cockade-like appearance.CONCLUSIONS: Endometrioid cancers are usually large, unilateral, multilocular-solid or solid tumors. The ultrasound characteristics of endometrioid carcinomas developing from endometriosis differ from those without evidence of tumor developing from endometriosis, the former being more often unilateral cysts with papillary projections and no ascites. (Less)

Despite some populations show a wide spectrum of different BRCA pathogenic variants (PVs), particular ethnic groups carry at high frequency a single or a few recurrent PVs, usually due to a founder effect. The identification of these founder PVs, with simple molecular methods, improves BRCA1/2 testing and cancer risk assessment. In this study, we developed a rapid and reliable PCR method, coupled with capillary electrophoresis (CE) for genotyping the Italian founder BRCA1 c.4964_4982del19 (rs80359876) variant. In addition, we compared the performance of two CE platforms: (Agilent 2100 Bioanalyzer and the Experion Automated Electrophoresis system) to identify this variant. Our findings suggest that CE represents a simple and standardized diagnostic strategy for the unambiguously identification of the BRCA1 c.4964_4982del19 variant, on both germline and somatic DNA samples. The results and performance obtained by two platforms are absolutely superimposable in terms of specificity and sensitivity, as well as for their feasibility, time of analysis and costs.

Objective Chemoradiation-based neoadjuvant treatment followed by radical surgery is an alternative therapeutic strategy for locally advanced cervical cancer (LACC) –stage ≥ IB2 (except of IIA1)– but ultrasound variables used to predict neoadjuvant partial response are not well defined. The goal of this study was to prospectively analyze the potential role of transvaginal ultrasound (TVUS) in early predicting pathologically assessed residual disease in a large, single-institution series of LACC patients triaged to neoadjuvant treatment followed by radical surgery. Methods Between October 2010 and June 2014, 108 women with histologically documented LACC were screened and 88 of them were included in the final analysis. Tumor volume, 3D power Doppler indices and contrast parameters were obtained before (baseline examination) and after two weeks of treatment (early examination). The pathological response was defined as complete (absence of any residual tumor after treatment) or partial, including both microscopic and macroscopic residual tumor at pathological examination. Comparisons between the two groups (complete response group versus partial response group) were made with Mann–Whitney-test or Wilcoxon-test and χ2-test, as appropriate. Receiver–operating characteristic (ROC) curves were generated for statistically significant ultrasound variables on univariate analysis to evaluate their diagnostic ability to predict pathological partial response. Results Complete and partial pathological responses to neoadjuvant therapy were documented in 40 (45.5%) and 48 (54.5%) patients respectively. At baseline examination, tumor volume did not differ between patients with a complete and those with a partial response. However, after two weeks of neoadjuvant treatment, the tumor volume was significantly higher in patients with partial response than in those with complete response (p = 0.019). Among the 3D vascular indices, vascularization index (VI) was significantly lower in partial response group than in complete response group both before and two weeks after treatment (p = 0.037 and p = 0.024 respectively). In the contrast analysis, a lower tumor peak enhancement (PE) as well as a lower tumor Wash in Rate (WiR), and a longer tumor Rise Time (RT) were observed at baseline examination in women with partial response than in those with complete response (p = 0.006, p = 0.003, p = 0.038, respectively). No difference was found in terms of contrast parameters at early examination. Receiver operating characteristic (ROC) curve analysis of baseline parameters showed that the best cut-off for predicting pathological partial response was 41.5% for VI (sensitivity 63.6% and specificity 66.7%); 16123.5 for tumor PE (sensitivity 47.9% and specificity 84.2%); 7.8 s for tumor RT (sensitivity 68.8% and specificity 57.9%); and 4902 for tumor WiR (sensitivity 77.1% and specificity 60.5%). ROC curves of early parameters showed that the best cut-off for predicting pathological partial response was 18.1 cm3 for tumor volume (sensitivity 71% and specificity 60%) and 39.5% for VI (sensitivity 63% and specificity 74%). Conclusions Ultrasound and contrast parameters differ between patients with complete response and those with partial response before and after two weeks of neoadjuvant treatment. However, neither ultrasound parameters performed before treatment nor those performed two weeks after treatment have shown a cut-off value with acceptable sensitivity and specificity for predicting pathological partial response to neoadjuvant therapy.

To analyse the role of DW-MRI in early prediction of pathologically-assessed residual disease in locally-advanced cervical cancer (LACC) treated with neoadjuvant chemoradiotherapy followed by radical surgery. Between October 2010–June 2014, 108 women with histologically-proven cervical cancer were screened; 88 were included in this study. Tumour volume (TV) and ADCmean were measured before (baseline-MRI) and after 2 weeks of chemoradiotherapy (early-MRI). According to histopathology, treatment response was classified as complete (CR) or partial (PR). Comparisons were made with Mann-Whitney, Wilcoxon and χ2 tests. ROC curves were generated for statistically significant parameters on univariate analysis. CR and PR were documented in 40 and 48 patients. At baseline-MRI, TV did not differ between groups. At early-MRI, TV was higher in PR than in CR (p=0.001). ΔTV reduction after treatment was lower in PR than in CR (63.6% vs. 81.1%; p=0.001). At baseline-MRI and early-MRI, ADCmean did not differ between PR and CR. ROC curve showed best cut-off for predicting pathological PR was ΔTV reduction of 73% with sensitivity, specificity, accuracy, NPV, PPV of 73%, 72.5%, 72.7%, 76%, 69%. TV evaluated before and early after treatment could predict pathological response in LACC. ADCmean did not correlate with treatment outcome. • Early-MRI tumour volume assessment could predict pathological response to nCRT in LACC. • Best cut-off for predicting pathological PR was ΔTV reduction of 73 %. • Early-MRI ADC mean measurements did not correlate with treatment outcome.

OBJECTIVES To describe clinical and ultrasound features of different subclasses of malignant serous ovarian tumors according to the World Health Organization 2014 classification. METHODS Patients with a histological diagnosis of borderline tumor (BOT), non-invasive and invasive low-grade serous carcinoma (LGSC) and high-grade serous carcinoma (HGSC), who had undergone preoperative ultrasound examination, were retrospectively identified from two ultrasound centers. The masses were described using the terms of the International Ovarian Tumor Analysis Group. RESULTS Sixty-four (15.8%) women had a serous BOT, 11 (2.7%) a non-invasive LGSC, 31 (7.6%) an invasive LGSC and 300 (73.9%) had a HGSC. The vast majority of BOTs (82.3%) and non-invasive LGSCs (90.9%) were Stage I according to the International Federation of Gynecology and Obstetrics (FIGO) classification scheme, whereas most invasive LGSCs (74.2%) and HGSCs (74.0%) were FIGO Stage III. On ultrasound examination, most borderline lesions were described as unilocular-solid (54.7%) or as multilocular-solid (29.7%) cysts. Papillary projections were present in 52 (81.3%) BOTs. Most non-invasive LGSCs (63.6%) were multilocular-solid cysts and 81.8% had papillary projections. Invasive LGSCs were multilocular-solid cysts in 54.8% of cases, and papillary projections were present in 32.3% of lesions. HGSCs were multilocular-solid (32.7%) or solid (64.0%) masses, with papillary projections in only 7% of cases. CONCLUSIONS Papillary projections were the most typical ultrasound feature of non-invasive (borderline and low-grade) malignant serous tumors, while the presence of solid components but few, if any, papillations was the most representative feature of invasive (low-grade and high-grade) serous tumors. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Objective To describe the clinical and ultrasound findings in patients with mucinous ovarian tumors. Methods In this retrospective study, women with a histological diagnosis of mucinous ovarian tumor who had undergone preoperative ultrasound examination were identified from the database of a single ultrasound center. The histological examination was performed by the same pathologist in all cases, and the ultrasound appearance of the tumors was described using the terms and definitions of the International Ovarian Tumor Analysis group. Results We identified 123 women with a histological diagnosis of mucinous ovarian tumor, of whom 57 (46%) had benign cystadenoma, 34 (28%) had gastrointestinal (GI)-type borderline tumor, 10 (8%) had endocervical-type borderline tumor and 22 (18%) had GI-type invasive carcinoma. On ultrasound examination, 65% (37/57) of cystadenomas were multilocular, of which 59% had ≤ 10 locules, and 79% (27/34) of GI-type borderline tumors were multilocular, of which 89% had > 10 locules. Conversely, 60% (6/10) of endocervical-type borderline tumors had papillations. Eighty-two percent (18/22) of invasive masses contained solid components and 55% (12/22) were multilocular-solid cysts. Bilateral mucinous cystadenomas were found in two women (4% of women with benign tumors) and bilateral borderline tumors of endocervical type in two women (20% of women with borderline tumors of endocervical type). No woman had a bilateral GI-type borderline tumor or a bilateral invasive tumor. Conclusions A multilocular cyst with 2–10 locules is representative of a benign cystadenoma, whereas a multilocular cyst with > 10 locules is indicative of a GI-type borderline tumor. Most invasive tumors of mucinous GI-type contain solid components, the most typical ultrasound appearance being that of a multilocular-solid tumor. Papillary projections are typical features of endocervical-type borderline tumors. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

We discuss the diagnosis and the management of endometrial carcinoma in a single horn of bicornuate uterus in a 64-year-old woman as a case report. The case underwent laparoscopic radical hysterectomy and bilateral iliac lymphadenectomy.The gross examination of the uterus revealed a bicornuate uterus with a greater horn of 12 × 9 × 8 cm and a smaller horn of 10 × 3 cm. The cavity of the greater horn showed a neoplastic growth of 10 cm with infiltration of about 1,8 cm of the myometrium from whole thickness of 1.9 cm. while the other horn was free of tumor tissue.The microscopic examination of the uterus revealed G2 endometrioid adenocarcinoma of the endometrium of the greater horn with infiltration of more than 50% of the myometrium.In the presence of bicornuate uterus, a bilateral endometrial biopsy should be performed in order to reduce the risk of delayed or missed diagnosis.The management of a case of bicornuate unicollis uterus with endometrial carcinoma in only one horn is the same as patients with endometrial cancer in single uterus and depends mainly on stage and histological grade of the tumor.The possibility of existence of a separate uterine cavity should always be considered when endometrial cancer is clinically suspected but pathology fails to confirm the diagnosis. This points out the importance of a careful physical examination and radiographic evaluation in such cases. Keywords: Bicornuate uterus, Endometrial cancer

OBJECTIVE: To describe the clinical and ultrasound characteristics of serous cystadenofibromas in the adnexa. METHODS: This was a retrospective study of patients identified in the International Ovarian Tumor Analysis (IOTA) database, who had a histological diagnosis of serous cystadenofibroma and had undergone preoperative ultrasound examination by an experienced ultrasound examiner, between 1999 and 2012. In the IOTA database, which contains data collected prospectively, the tumors were described using the terms and definitions of the IOTA group. In addition, three authors reviewed, first independently and then together, ultrasound images of serous cystadenofibromas and described them using pattern recognition. RESULTS: We identified 233 women with a histological diagnosis of serous cystadenofibroma. In the IOTA database, most cystadenofibromas (67.4%; 157/233) were described as containing solid components but 19.3% (45/233) were described as multilocular cysts and 13.3% (31/233) as unilocular cysts. Papillary projections were described in 52.4% (122/233) of the cystadenofibromas. In 79.5% (97/122) of the cysts with papillary projections, color Doppler signals were absent in the papillary projections. Most cystadenofibromas (83.7%; 195/233) manifested no or minimal color Doppler signals. On retrospective analysis of 201 ultrasound images of serous cystadenofibromas, using pattern recognition, 10 major types of ultrasound appearance were identified. The most common pattern was a unilocular solid cyst with one or more papillary projections, but no other solid components (25.9%; 52/201). The second most common pattern was a multilocular solid mass with small solid component(s), but no papillary projections (19.4%; 39/201). The third and fourth most common patterns were multi- or bilocular cyst (16.9%; 34/201) and unilocular cyst (11.9%; 24/201). Using pattern recognition, shadowing was identified in 39.8% (80/201) of the tumors, and microcystic appearance of the papillary projections was observed in 34 (38.6%) of the 88 tumors containing papillary projections. CONCLUSIONS: The ultrasound features of serous cystadenofibromas vary. The most common pattern is a unilocular solid cyst with one or more papillary projections but no other solid components, with absent color Doppler signals. Most serous cystadenofibromas were poorly vascularized on color Doppler examination and many manifested acoustic shadowing. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd. ispartof: ULTRASOUND IN OBSTETRICS & GYNECOLOGY vol:54 issue:6 pages:823-830 ispartof: location:England status: published

Objective This study is aimed to analyze the clinical outcome of recurrent ovarian cancer patients bearing isolated lymph-node recurrence (ILNR) who underwent salvage lymphadenectomy (SL). The prognostic role of clinicopathological variables and the mutational status of BRCA1/2 have also been investigated. Methods This retrospective, single-institutional study included women with platinum-sensitive lymph node recurrence underwent to SL between June 2008 and June 2018. Univariate and multivariate analysis was performed to evaluate the impact of clinical parameters, and BRCA1/2 mutational status on post salvage lymphadenectomy progression-free survival (PSL-PFS). Results As of June 2019, the median follow-up after SL was 30 months, and the relapse has been documented in 48 (56.5%) patients. In the whole series, the median PSL-PFS was 21 months, and the 3-year PSL-PFS was 36.7%. The median PSL-PFS, according to patients with ILNR (N = 71) versus patients with lymph-nodes and other sites of disease (N = 14), was 27 months versus 12 months, respectively. Univariate analysis of variables conditioning PSL-PFS showed that platinum-free interval (PFI) ≥12 months, normal Ca125 serum levels, and number of metastatic lymph-nodes ≤3 played a statistically significant favorable role. In multivariate analysis, PFI duration ≥12 months and the number of metastatic lymph nodes ≤3 were shown to keep their favorable, independent prognostic value on PSL-PFS. Conclusions In the context of SL, the patients with long PFI and low metastatic lymph node numbers at ILNR diagnosis have the best outcome. The BRCA mutational status seems not associated with clinical variables and PSL-PFS, differently from other sites of disease in ROC patients.

Introduction/Background To describe accurately the oncological outcomes after hepatic resection (HR) in recurrent ovarian carcinoma (ROC) evaluating clinic-pathological variables and mutational status of BRCA1/2. Although HR is considered a challenging situation in ROC patients, assessment of BRCA1/2 mutational status seems to have a relevant clinical value to guide surgical therapy. Methodology Patients who underwent HR for ROC at the Catholic University of Rome, between June 2012 and October 2017 were included. Exclusion criteria were represented by extra-abdominal disease and presence of diffuse peritoneal carcinomatosis requiring more than 2 bowel resections. Details relative to HR were collected and BRCA analysis was performed. Predictive factors for of post-relapse progression free survival (PHR-PFS)were assessed by univariate analyses using Cox-proportional hazard regression models. Results Thirty-four patients undewent HR within secondary cytoreductive surgery (SCS). Six patients (17.6%) presented with hepatic relapse only, while the remaining 28 patients (82.4%) had concomitant extra-hepatic disease. In the whole series, the 3-yr PHR-PFS was 49.1% and the 3-yr progression free survival overall survivalwas 72.9%. Univariate analysis of variables conditioning PHR-PFS showed that only BRCA mutational status played a statistically significant favourable role: the 3-yr PHR-PFS rate was 81.0% in BRCA mutated patient compared to15.2% in wild type ones (p value: 0.001). Conclusion Our clinical analyses suggest that in ROC patients with liver disease the assessment of BRCA mutational status can help to select patients elegible for SCS. Disclosure Nothing to disclose.

Objectives To describe accurately the oncological outcomes after hepatic resection (HR) in recurrent ovarian carcinoma (ROC) evaluating clinic-pathological variables and mutational status of BRCA1/2. Although HR is considered a challenging situation in ROC patients, assessment of BRCA1/2 mutational status seems to have a relevant clinical value to guide surgical therapy. Methods Patients who underwent HR for ROC at the Catholic University of Rome, between June 2012 and October 2017 were included. Exclusion criteria were represented by extra-abdominal disease and presence of diffuse peritoneal carcinomatosis requiring more than 2 bowel resections. Details relative to HR were collected and BRCA analysis was performed. Predictive factors for of post-relapse progression free survival (PHR-PFS)were assessed by univariate analyses using Cox-proportional hazard regression models. Results Thirty-four patients undewent HR within secondary cytoreductive surgery (SCS). Six patients (17.6%) presented with hepatic relapse only, while the remaining 28 patients (82.4%) had concomitant extra-hepatic disease. In the whole series, the 3-yr PHR-PFS was 49.1% and the 3-yr progression free survival overall survivalwas 72.9%. Univariate analysis of variables conditioning PHR-PFS showed that only BRCA mutational status played a statistically significant favourable role: the 3-yr PHR-PFS rate was 81.0% in BRCA mutated patient compared to15.2% in wild type ones (p value: 0.001). Conclusions Our clinical analyses suggest that in ROC patients with liver disease the assessment of BRCA mutational status can help to select patients elegible for SCS.

Objectives We compared the traditional ultrastaging (SU) with the one-step nucleic acid amplification (OSNA) for the detection of sentinel lymph node (SLN) metastasis in women with apparent early stage endometrial carcinoma (EC). Methods All women were surgically staged including SLN mapping. Nodes were cut perpendicular to the long axis and two adjacent 5 mm sections were cut at each of 2 levels 50 mm apart, and one slide was stained with H&E and the other with immunohistochemistry using the AE1/AE3 anticytokeratin antibody, and one negative control slide for a total of five slides per block. For OSNA analysis, the 2mm sections of the SLN were homogenized to form a lysate that was centrifuged and inserted into the RD100i instrument where for the isothermal amplification of CK19 mRNA. Results Totally 409 patients were included in the analysis (183 OSNA, 226 SU). Overall, 3521 lymph nodes were removed, of those 871 SLN’s (24.7%) were identified (381 OSNA, 490 SU). Sixty patients had metastasis on SLN’s (26 OSNA, 34 SU). Macrometastasis, micrometastases, and ITC were 25.7%, 68.6% and 5.7% for OSNA; 48.1%, 36.5% and 15.4% for SU (p = 0.015). ITC alone were recorded in 7 women (2 OSNA, 5 SU). Conclusions The OSNA assay detected a higher rate of micrometastasis and a lower rate macrometastasis and ITC compared to SU. The clinical and prognostic impact of ITC is still controversial. Further studies are needed to clarify the clinical impact of the OSNA assessment technique and the prognostic impact of ITC in patients with stage I EC.

This prospective study aimed to evaluate whetherBetween October 2010 and June 2014, 88 patients with LACC were enrolled. For each patient, threeAt histopathology, 40 patients had complete response (CR, pR0), 48 had partial response (PR: 21 microscopic [pR1] and 27 macroscopic [pR2]). At baseline, SUVIn LACC patients treated with CRT followed by surgery, early variations in metabolic parameters effectively discriminate histopathological PR of the primary tumor, suggesting the potential role of

This prospective study aimed to evaluate whether 18F-FDG-PET/CT performed before, during and after neoadjuvant chemo-radiotherapy (CRT) could predict histopathological response in patients with locally advanced cervical cancer (LACC) treated with CRT followed by radical surgery. Between October 2010 and June 2014, 88 patients with LACC were enrolled. For each patient, three 18F-FDG-PET/CT scans (baseline, early and final) were acquired and evaluated by qualitative and quantitative analysis. Maximum standardized uptake value (SUVmax), SUVmean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were measured as absolute values and their percentage variation (delta) (early vs. baseline and final vs. baseline). The role of 18F-FDG-PET/CT in predicting lymph node (LN) residual disease was evaluated by qualitative analysis only. Histopathology was the reference standard. At histopathology, 40 patients had complete response (CR, pR0), 48 had partial response (PR: 21 microscopic [pR1] and 27 macroscopic [pR2]). At baseline, SUVmax and SUVmean were significantly higher in pR0 than in pR1–pR2 patients. At early evaluation, MTV and TLG were significantly higher in pR1–pR2 than in pR0 patients. At final evaluation, SUVmax, SUVmean and TLG were significantly higher in pR1–pR2 than in pR0 patients. Delta SUV parameters and delta TLG were significantly lower in PR group both during and after CRT. Delta MTV was significantly lower in patients with PR in the early phase only. In receiver operating characteristic (ROC) curve analysis, baseline SUVmean, early delta TLG, and final delta SUVmax better discriminated PR, providing 83.3%, 67.6% and 85% positive predictive value (PPV) and 60.3%, 90% and 70.8% negative predictive value (NPV), respectively. For LN assessment, high NPV was observed at early and final 18F-FDG-PET/CT (93.5% and 92.3%, respectively). In LACC patients treated with CRT followed by surgery, early variations in metabolic parameters effectively discriminate histopathological PR of the primary tumor, suggesting the potential role of 18F-FDG-PET/CT in early personalized treatment. The high NPV of early and final PET/CT could enable “tailored surgery” by avoiding lymphadenectomy in selected patients.

OBJECTIVE To compare the ultrasound characteristics of patients with synchronous primary cancers of the endometrium and ovary vs those of patients with endometrial cancer with ovarian metastasis. METHODS This was a single-institution retrospective observational study of patients with a histological diagnosis of endometrial cancer and an ovarian malignant mass, who had undergone preoperative ultrasound examination at our unit. Based on the histological diagnosis, patients were classified into two groups: those with synchronous primary cancers of the endometrium and ovary (synchronous group) and patients with endometrial cancer with ovarian metastasis (metastasis group). We compared the ultrasound features of ovarian malignant masses and of endometrial cancers between the two groups. Student's t-test, Mann-Whitney U-test, χ2 test or Fisher's exact test were used for comparisons of variables between the two histological groups, as appropriate. RESULTS We identified 131 patients, of whom 51 had synchronous primary cancers of the endometrium and ovary (synchronous group) and 80 had endometrial cancer with ovarian metastasis (metastasis group). On ultrasound examination, ovarian masses in the synchronous group were more often multilocular-solid and less often bilateral than those in the metastasis group. With respect to the ultrasound features of the endometrial lesions, the median largest diameter was 29 (range, 11-118) mm in the synchronous group in comparison with 51.5 (range, 6-150) mm in the metastasis group (P

Objective: To evaluate the clinical accuracy of Hepika test to identify cancer/precancerous lesions of the uterine cervix. Materials and Methods: A multicentre retrospective study was carried out in 2018 and included 330 liquid-based cytology samples from three Italian centres of women aged 25–64 who had been tested for the human papillomavirus (HPV) and whose histology or follow-up outcome was known. Hepika is an enzyme-linked immunosorbent assay (ELISA) targeting the protein complexes E6#p53 and E7#pRb. After excluding samples without sufficient residual material, the clinical accuracy of Hepika test was evaluated in 274 samples: adenocarcinoma (ADC) (4), squamous cell carcinoma (SCC) (7), adenocarcinoma in situ (AIS) (1), cervical intraepithelial neoplasia (CIN) grade 3 (60), CIN2 (51), CIN1 (34), and negative histology (117). Association, sensitivity, and specificity for carcinoma, CIN3+ and CIN2+ are reported. Results: Positive Hepika test was associated with a high probability of carcinoma (odds ratio (DOR) = 33.68, 95% confidence interval (CI) 7.0–163.1), sensitivity was 81.8%, specificity, 88.2%. A positive Hepika test showed a weaker association with CIN3+ lesions (DOR = 3.5, 95% CI 1.75–6.99) and lower sensitivity (27.8%). Conclusion: The Hepika test was found to be an accurate biomarker for HPV-induced cervical carcinoma. Population-based prospective studies are needed to confirm the clinical usefulness of the Hepika test in the differential diagnosis of HPV-induced invasive lesions.

Objective To describe the clinical and ultrasound characteristics of uterine sarcomas. Methods This was a retrospective multicenter study. From the databases of 13 ultrasound centers, we identified patients with a histological diagnosis of uterine sarcoma with available ultrasound reports and ultrasound images who had undergone preoperative ultrasound examination between 1996 and 2016. As the first step, each author collected information from the original ultrasound reports from his/her own center on predefined ultrasound features of the tumors and by reviewing the ultrasound images to identify information on variables not described in the original report. As the second step, 16 ultrasound examiners reviewed the images electronically in a consensus meeting and described them using predetermined terminology. Results We identified 116 patients with leiomyosarcoma, 48 with endometrial stromal sarcoma and 31 with undifferentiated endometrial sarcoma. Median age of the patients was 56 years (range, 26-86 years). Most patients were symptomatic at diagnosis (164/183 (89.6%)), the most frequent presenting symptom being abnormal vaginal bleeding (91/183 (49.7%)). Patients with endometrial stromal sarcoma were younger than those with leiomyosarcoma and undifferentiated endometrial sarcoma (median age, 46 years vs 57 and 60 years, respectively). According to the assessment by the original ultrasound examiners, the median diameter of the largest tumor was 91 mm (range, 7-321 mm). Visible normal myometrium was reported in 149/195 (76.4%) cases, and 80.0% (156/195) of lesions were solitary. Most sarcomas (155/195 (79.5%)) were solid masses (> 80% solid tissue), and most manifested inhomogeneous echogenicity of the solid tissue (151/195 (77.4%)); one sarcoma was multilocular without solid components. Cystic areas were described in 87/195 (44.6%) tumors and most cyst cavities had irregular walls (67/87 (77.0%)). Internal shadowing was observed in 42/192 (21.9%) sarcomas and fan-shaped shadowing in 4/192 (2.1%). Moderate or rich vascularization was found on color-Doppler examination in 127/187 (67.9%) cases. In 153/195 (78.5%) sarcomas, the original ultrasound examiner suspected malignancy. Though there were some differences, the results of the first and second steps of the analysis were broadly similar. Conclusions Uterine sarcomas typically appear as solid masses with inhomogeneous echogenicity, sometimes with irregular cystic areas but only very occasionally with fan-shaped shadowing. Most are moderately or very well vascularized. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

To investigate ultrasound features and the best cut-off value of the cancer antigen 125/carcinoembryonic antigen (CA125/CEA) ratio to discriminate ovarian metastases from benign and primary malignant ovarian neoplasms in two selected groups of morphological ovarian masses, namely multilocular masses with five or more locules and multilocular-solid masses.Patients with multilocular (five or more locules) or multilocular-solid ovarian masses, operated on within 3 months of ultrasound examination, and with tumor markers (CEA and CA125) available at diagnosis, were identified retrospectively from three ultrasound centers. The masses were described using the International Ovarian Tumor Analysis (IOTA) terminology. Ultrasound and clinical characteristics were compared between those with an ovarian neoplasm (including benign and primary malignant neoplasms) and those with an ovarian metastasis. Receiver-operating characteristics curve (ROC) analysis was used to evaluate the ability of CA125, CEA and CA125/CEA to differentiate between ovarian neoplasms and ovarian metastases, and their predictive performance was assessed.In total, 350 (88.4%) patients with an ovarian neoplasm (including 99 benign, 43 borderline and 197 primary epithelial ovarian carcinomas, seven malignant rare tumors and four other types of invasive ovarian tumor) and 46 (11.6%) patients with an ovarian metastasis were analyzed. On ultrasound examination, ovarian neoplasms were smaller than ovarian metastases (median largest diameter, 97 (range, 20-387) mm vs 146 (range, 43-259) mm, respectively; P 0.0001) and presented with a lower number of cysts with 10 locules (18.9% vs 54.3%; P 0.0001). ROC curve analysis showed that the best cut-off value of CEA for distinguishing between ovarian neoplasms and ovarian metastases was 2.33 ng/mL. The predictive performance of this CEA cut-off value was: area under the curve (AUC), 0.791 (95% CI, 0.711-0.870); accuracy, 73.7%; sensitivity, 73.1%; specificity, 78.3%; positive predictive value (PPV), 96.2%; and negative predictive value (NPV), 27.7%. The best cut-off value of CA125/CEA for distinguishing between ovarian neoplasms and ovarian metastases was 11.92. The predictive performance of this CA125/CEA cut-off value was: AUC, 0.758 (95% CI, 0.683-0.833); accuracy, 79.8%; sensitivity, 82.3%; specificity, 60.9%; PPV, 94.1%; and NPV, 31.1%.CA125/CEA ratio and CEA alone did not show any significant difference in their ability to distinguish between ovarian neoplasms (including benign and malignant) and ovarian metastases in masses with multilocular and those with multilocular-solid morphology. Therefore, in this morphological subgroup of ovarian masses, CEA alone is sufficient to differentiate between ovarian neoplasms and ovarian metastases. Copyright © 2018 ISUOG. Published by John WileySons Ltd.

A case of stage IB2 cervical cancer at 27 weeks of pregnancy, treated with neoadjuvant chemotherapy followed by radical Cesarean hysterectomy with full pelvic and infra-mesenteric lymphadenectomy, and adjuvant chemo-radiation is described. While she remains without disease, her baby was diagnosed with acute myelogenous leukemia. We highlight the pre-operative work-up, treatment options, safety, feasibility, and outcomes for the mother and her fetus.

Objectives To describe clinical history and ultrasound findings in patients with tubal carcinoma. Methods Patients with a histological diagnosis of tubal cancer who had undergone preoperative ultrasound examination were identified from the databases of 13 ultrasound centers. The tumors were described by the principal investigator at each contributing center on the basis of ultrasound images, ultrasound reports and research protocols (when applicable) using the terms and definitions of the International Ovarian Tumor Analysis (IOTA) group. In addition, three authors reviewed together all available digital ultrasound images and described them using subjective evaluation of gray-scale and color Doppler ultrasound findings. Results We identified 79 women with a histological diagnosis of primary tubal cancer, 70 of whom (89%) had serous carcinomas and 46 (58%) of whom presented at FIGO stage III. Forty-nine (62%) women were asymptomatic (incidental finding), whilst the remaining 30 complained of abdominal bloating or pain. Fifty-three (67%) tumors were described as solid at ultrasound examination, 14 (18%) as multilocular solid, 10 (13%) as unilocular solid and two (3%) as unilocular. No tumor was described as a multilocular mass. Most tumors (70/79, 89%) were moderately or very well vascularized on color or power Doppler ultrasound. Normal ovarian tissue was identified adjacent to the tumor in 51% (39/77) of cases. Three types of ultrasound appearance were identified as being typical of tubal carcinoma using pattern recognition: a sausage-shaped cystic structure with solid tissue protruding into it like a papillary projection (11/62, 18%); a sausage-shaped cystic structure with a large solid component filling part of the cyst cavity (13/62, 21%); an ovoid or oblong completely solid mass (36/62, 58%). Conclusions A well vascularized ovoid or sausage-shaped structure, either completely solid or with large solid component(s) in the pelvis, should raise the suspicion of tubal cancer, especially if normal ovarian tissue is seen adjacent to it. Copyright (C) 2013 ISUOG. Published by John Wiley & Sons Ltd. (Less)

Low grade appendiceal mucinous neoplasms (LAMNs) include all mucinous tumors of the appendix without an infiltrative histological pattern, either confined to the appendix or that have spread to the peritoneum (pseudomyxoma peritoneii), according to the WHO Classification1 (Suppl 1). The ovarian involvement from LAMN is not uncommon and in most cases is the first evidence of primitive LAMNs. Metastatic LAMNs to the ovary are more indolent and have a better prognosis than metastatic appendiceal adenocarcinomas.2

Background Malignant transformation has been reported in approximately 1% of the endometriosis cases; herein, we report a case of clear cell endometrial carcinoma arising from endometriosis foci located within a caesarean section scar. Case presentation In November 2014, a Caucasian, 44-year-old woman was transferred to our institution because of severe respiratory failure due to massive lung embolism and rapid enlargement of a subcutaneous suprapubic mass. Abdomino-pelvic magnetic resonance showed a 10.5 × 5.0 × 5.0 cm subcutaneous solid mass involving the rectus abdominis muscle. Pelvic organs appeared normal, while right external iliac lymph nodes appeared enlarged (maximum diameter = 16 mm). A whole-body positron emission tomography/computed tomography scan showed irregular uptake of the radiotracer in the 22 cm mass of the abdominal wall, and in enlarged external iliac and inguinal lymph nodes. In December 2014, the patient underwent exploratory laparoscopy showing normal adnexae and pelvic organs; peritoneal as well as cervical, endometrial and vesical biopsies were negative. The patient was administered neo-adjuvant chemotherapy with carboplatin and paclitaxel, weekly, without benefit and then underwent wide resection of the abdominal mass, partial removal of rectus abdominis muscle and fascia, radical hysterectomy, bilateral salpingo-oophorectomy, and inguinal and pelvic lymphadenectomy. The muscular gap was repaired employing a gore-tex mesh while the external covering was made by a pedicled perforator fasciocutaneous anterolateral thigh flap. Final diagnosis was clear cell endometrial adenocarcinoma arising from endometriosis foci within the caesarean section scar. Pelvic and inguinal lymph nodes were metastatic. Tumor cells were positive for CK7 EMA, CKAE1/AE3, CD15, CA-125, while immunoreaction for Calretinin, WT1, estrogen, and progesterone receptors, cytokeratin 20, CD10, alpha fetoprotein, CDX2, TTF1, and thyroglobulin were all negative. Liver relapse occurred after 2 months; despite 3 cycles of pegylated liposomal doxorubicin (20 mg/m2, biweekly administration), the death of the patient disease occurred 1 month later. Conclusions Attention should be focused on careful evaluation of patient history in terms of pelvic surgery, and symptoms suggestive of endometriosis such as repeated occurrence of endometriosis nodules at CS scar, or cyclic pain, or volume changes of the nodules.

Neoadjuvant chemotherapy (NACT) has been recognized as a reliable therapeutic strategy in patients with unresectable advanced epithelial ovarian cancer (EOC). The molecular events leading to platinum (Pt) response in NACT settings have hitherto not been explored. In the present work, longitudinal changes of miRNA expression profile were investigated to identify miRNA families with prognostic role in high-grade serous EOC patients who received the NACT regimen.One hundred sixty-four matched tumor biopsies taken at initial laparoscopic evaluation and at interval-debulking surgery (IDS) after four courses of Pt-based therapy were selected from 82 stage IIIC-IV high-grade serous-EOC patients that were judged unsuitable for complete primary debulking and subjected the NACT protocol. miRNA profiling by microarray, real-time PCR and immuno-histochemical staining for Smad2 phosphorylation (P-Smad2) were used for data analysis.Analysis revealed that 369 miRNAs were differentially expressed in matched biopsies (referred to as DEMs). DEMs were not scattered across the genome, but clustered into families: miR-199, let-7, miR-30, miR-181 and miR-29. Multivariate analysis showed that miR-199a-3p, miR-199a-5p, miR-181a-5p and let-7g-5p associated with overall and progression-free survival (P0.05); miR-199a-3p, miR-199a-5p and miR-181a-5p associated with residual tumor volume and Pt-free interval (P0.05). Immuno-histochemical staining confirmed an enrichment of P-Smad2, a marker of transforming growth factor-β activation, in tumors from patients with shorter PFS and OS, and with high levels of expression of miR-181a-5p (P0.05). Kaplan-Meier curves plotting concomitant expression of P-Smad2 and miR-181a-5p show significant differences in PFS and OS compared with those depicting the expression of each biomarker alone (P0.001).This study describes several miRNA families with a prognostic role in the NACT setting. It also confirms that concomitant analysis of P-Smad2 and miR-181a-5p in surgical samples may be capable of identifying those ovarian cancer patients with poor outcome and little chance of response to Pt-based NACT.