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Objective The aim of this study was to investigate the correlation between BRCA mutational status and response to bevacizumab in a large advanced ovarian cancer (AOC) series. Methods This is a multicenter, retrospective case-control study including upfront AOC treated between January 2015 and June 2019. The main inclusion criteria were: having received three weekly carboplatin-paclitaxel as first-line treatment, with or without Bevacizumab maintenance, knowledge of the BRCA mutational status. Results Overall, 441 patients were included; 183 (41.5%) patients received bevacizumab (Cases), and 258 (58.5%) did not receive it (Controls). The BRCA mutated patients (BRCAmut) were 58 (39%) in the Cases group and 90 (34.9%) in the Controls group (p = .77). Patients who received bevacizumab had a significant 4-months increase in median progression free survival (mPFS: 21 vs. 17 months, p = .033). Concerning BRCAmut patients, no differences were shown between those who received bevacizumab or not in terms of mPFS (24 vs. 22 months, p = .3). Conversely, in BRCA wild-type (BRCAwt) population bevacizumab administration significantly prolonged mPFS (20 vs 15 months, p = .019). At multivariate analysis, independent factors of prolonged PFS were BRCA status (OR = 0.60), having received PDS (OR = 0.69), and complete cytoreduction (OR = 0.50), but not the bevacizumab administration (OR = 0.83, p = .22). Conclusions No evidence of oncological benefit in terms of PFS and OS related to bevacizumab maintenance therapy was found in BRCAmut patients. Differently, BRCAwt patients seem to benefit from antiangiogenic treatment in terms of mPFS.

Objective This review aims to analyze the pathological aspects, diagnosis and treatment of rare mesenchymal uterine tumors. Methods On August 2019, a systematic review of the literature was done on Pubmed, MEDLINE, Scopus, and Google Scholar search engines. The systematic review was carried out in agreement with the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes statement (PRISMA). The following words and key phrases have been searched: "endometrial stromal sarcoma", "low-grade endometrial stromal sarcoma", "high-grade endometrial stromal sarcoma", "uterine sarcoma", "mesenchymal uterine tumors" and "uterine stromal sarcoma". Across these platforms and research studies, five main aspects were analyzed: the biological characteristics of the neoplasms, the number of cases, the different therapeutic approaches used, the follow-up and the oncological outcomes. Results Of the 94 studies initially identified, 55 were chosen selecting articles focusing on endometrial stromal sarcoma. Of these fifty-five studies, 46 were retrospective in design, 7 were reviews and 2 randomized phases III trials. Conclusion Endometrial stromal sarcomas are rare mesenchymal uterine neoplasms and surgery represents the standard treatment. For uterus-limited disease, the remove en bloc with an intact resection of the tumor (without the use of morcellation) is strongly recommended. For advanced-stage disease, the standard surgical treatment is adequate cytoreduction with metastatectomy. Pelvic and para-aortic lymphadenectomy is not recommended in patients with Low-grade Endometrial Stromal Sarcoma (ESS), while is not clear whether cytoreduction of advanced tumors improves patient survival in High-grade ESS. Administration of adjuvant radiotherapy or chemotherapy is not routinely used and its role is still debated.

In recent years, ovarian cancer (OC) treatment has been enriched with many new target therapies, most of all antiangiogenic drugs and PARP inhibitors (PARPis), which have literally changed the natural history of the disease. The impressive results of immunotherapy in other malignancies, mainly melanoma and lung cancer, and the good signals of activity in gynecological neoplasms like cervical and microsatellite instable (MSI-H) endometrial cancer, opened the space to the introduction of immune-stimulatory drugs in ovarian cancer.The goal of this article is to summarize the newest evidence on the use of immune check point inhibitors in OC trying to explain why, at present, this strategy has failed to improve clinical outcome and focusing on the possible strategies to overcome treatment failure.Although numerous trials have been undertaken, only scanty results have been obtained so far with immune check-point inhibitors (ICIs) in OC either when used as single agents or in combination with antiangiogenic therapy and ongoing trials are exploring the association of ICIs with PARPis and other ICIs. A better knowledge of predictive biomarkers of response and mechanisms of immunotherapy resistance, will help in identifying the most appropriate population to treat with ICIs.

Immunotherapy has changed the natural history of several malignancies that, a decade ago, had a very poor prognosis, such as lung cancer and melanoma. Consequently, many attempts have been done to expand the indications of immunotherapy agents, predominantly immune checkpoint inhibitors (ICIs), in other cancers, including gynecological malignancies. Alongside promising results in cervical and endometrial neoplasms, there are not clear data on the benefit of ICIs as single agent or in combination with antiangiogenic agents in ovarian cancer (OC) and ongoing trials are focusing on combining ICIs with standard chemotherapy or PARP inhibitors. This chapter summarized the evidences of ICIs in gynecological malignancies and report the ongoing trials in cervical, endometrial and OC.

The aim of this retrospective study is to analyze the prognostic role and the practical implication of mesenteric lymph nodes (MLN) involvements in advanced ovarian cancer (AOC). A total of 429 patients with AOC underwent surgery between December 2007 and May 2017. We included in the study 83 patients who had primary (PDS) or interval debulking surgery (IDS) for AOC with bowel resection. Numbers, characteristics and surgical implication of MLN involvement were considered. Eighty-three patients were submitted to bowel resection during cytoreduction for AOC. Sixty-seven patients (80.7%) underwent primary debulking surgery (PDS). Sixteen patients (19.3%) experienced interval debulking surgery (IDS). 43 cases (51.8%) showed MLN involvement. A statistic correlation between positive MLN and pelvic lymph nodes (PLN) (p = 0.084), aortic lymph nodes (ALN) (p = 0.008) and bowel infiltration deeper than serosa (p = 0.043) was found. A longer overall survival (OS) and disease-free survival was observed in case of negative MLN in the first 20 months of follow-up. No statistical differences between positive and negative MLN in terms of operative complication, morbidity, Ca-125, type of surgery (radical vs supra-radical), length and site of bowel resection, residual disease and site of recurrence were observed. An important correlation between positive MLN, ALN and PLN was detected; these results suggest a lymphatic spread of epithelial AOC similar to that of primary bowel cancer. The absence of residual disease after surgery is an independent prognostic factor; to achieve this result should be recommended a radical bowel resection during debulking surgery for AOC with bowel involvement.

Introduction/Background Endometrial cancer is the most frequently diagnosed gynecological tumor with more than 60.000 new cases each year. Following the ESMO-ESGO-ESTRO consensus conference, patients are classified in different classes of risk for lymph node metastases based on the instrumental suspected stage of the disease. In this scenario, a correct pre-operative workup is essential for a proper planning treatment offered to the patient. Although most of the oncological centers have replaced the MRI with trans-vaginal ultrasound, this, in the international guidelines, is considered only in the fertility sparing and in cases of contraindicated MRI. The Aim of our study is to evaluate the diagnostic accuracy of transvaginal ultrasonography in relation to confoundable factors that may affect its quality, to a proper patient risk stratification and a consequent better surgical strategy. Methodology The study analyzed 290 patients with histological diagnosis of endometrial adenocarcinoma. Each patient was subjected to the anamnestic collection, chest/abdomen/pelvis CT, assessment of Ca-125 and transvaginal ultrasound. The tumor ultrasound description was made according to IETA terminology. According to the FIGO staging system, the depth of myometrial invasion was rated as superficial (M1, 50%). Results Of the 272 patients included in the study in 214 (78.7%), there was an agreement between the depth of ultrasound myometrial infiltration and definitive histological examination. The FIGO stage IB (figure 1) was the main statistically significant confounding factor in the univariate analysis about ultrasound myometrial infiltration diagnosis (p=0.004). Fibromatosis and/or adenomyosis was significantly associated with a discordant ultrasonographic diagnosis in univariate analysis (p=0.04). Conclusion The study shows a high concordance between transvaginal ultrasonography and definitive histological examination in predicting myometrial infiltration, with 86,8% sensitivity (CI: 81.1–91), 64.4% specificity. Myometrial infiltration over 50% (Figo stage IB) represents the main confounding factor. Disclosure Nothing to disclose.

Introduction/Background Obesity represents a major health problem. Several studies reported that morbid obesity is associated with an 81% greater health care expenditure per capita compared with normal weight adults in the US. Although many articles have investigated costs of laparoscopic versus open approach for endometrial cancer, very few data are available in selected population of patients, such as obese women. The aim of this study has been to evaluate pre-, intra- and post-operative costs in obese women affected by endometrial cancer comparing laparoscopic versus open abdominal surgery. Methodology Economic expenditure in pre-operative, intra-operative and post-operative phases of the selected patients was evaluated. Costs were analyzed for all blood tests, instrumental examinations, consultations, operating materials, drugs, gynecological examinations, hospital stay, intensive care hospitalization and management of operative complications. Results The average length of stay was longer for patients operated by laparotomy with an almost double median hospitalization cost in the open abdominal group compared to the laparoscopic group (€ 4805.37 vs. € 2589.25; p Conclusion This study shows that in obese patients with endometrial cancer, minimally invasive surgery is more advantageous both in terms of costs and post-operative complications. Laparoscopic surgery in obese patients allows an economic saving of about 60% less than open surgery. Disclosure Nothing to disclose

Introduction/Background Vulvar cancer often requires radical vulvectomy with subsequent vulvar flap due to tumor aggressiveness and a high percentage of relapses. Approximately in 20–60% of cases, there are post-operative complications ranging from infection to wound dehiscence, lymphocele and flap necrosis that often require reoperation. Several methods have been described to verify the vitality of the flap, especially in plastic surgery, but these are often expensive and require specific machinery that is not generally present in a gynecological clinic. We present a viability verification of V-Y fasciocutaneous advancement flap for vulvar reconstruction by Endoscopic Near-Infrared and Indocyanine Green. Methodology The patient was a 67-year-old woman with FIGO IB ≤ 4 cm squamous cell vulvar cancer with the absence of inguinal lymphadenopathy. The lesion appeared about 35 mm from the lateral margin of the large left lip and extended to the left inguinocrural fold (figure 1). The patient underwent left inguinal lymphadenectomy and left radical hemivulvectomy with a left fasciocutaneous medial-thigh advancement flap. For the evaluation of the flap, we endovenous administered 50 mg of Indocyanine Green diluted in 10 ml of saline solution. After 10 minutes we visualized the flap margin with a near-infrared laparoscopic view and we noticed a tracer uptake on the whole edge of the flap, the perforating branches were also evident. The evaluation was repeated at the end of the surgical procedure and we confirmed the good vascularization of the flap (figure 2). Results No early or late post-operative complications were obtained. There was no wound dehiscence, marginal necrosis or surgical site infection. The patient stated satisfaction of the aesthetic level obtained. Conclusion Verifying the viability of the vulvar flap using near-infrared laparoscopic optics was easy to use, reproducible and extremely economical technique. This could be an extremely useful and reproducible alternative to other more expensive techniques. Disclosure Nothing to disclose

IntroductionSentinel lymph node (SLN) dissection has been recognized as a valid tool for staging in patients with endometrial cancer. Several factors are predictors of recurrence and survival in endometrial cancer, including positive lymphovascular space invasion. The aim of this study is to formulate a pre-operative score that, in the event of no-SLN identification, may give an estimate of the true probability of lymphovascular space invasion and guide management.MethodologyThis was a multi-institutional retrospective study conducted from January 2007 to December 2017. We included all patients with any grade endometrial tumor with a complete pathological description of the surgical specimen and with a minimum follow-up of 12 months. All patients underwent a class A hysterectomy according to Querleu and Morrow and bilateral salpingo-oophorectomy. Lymphadenectomy was performed based on patient risk of node metastases. In order to verify the predictive capacity of the parameters associated with lymphovascular space invasion status, grading, abnormal CA125 (>35 units/ml), myometrial invasion, and tumor size, a synthetic score was calculated. The score was introduced in the receiver operating characteristic curve model in which the binary classifier was represented by the lymphovascular space invasion status. The ideal cut-off was calculated with the determination of the Youden index. Sensitivity and negative predictive value of lymphovascular space invasion score was calculated in patients with lymph node metastasis.ResultsSix hundred and fourteen patients were included in the study. The average age and BMI of patients were 64.8 (range 33–88) years and 30.1 (range 17–64) respectively. Of the 284 patients who underwent lymphadenectomy, 231 (81.3%) patients had no lymph node metastases, 33 (11.6%) patients had metastatic pelvic lymph nodes, 12 (4.2%) patients had metastatic aortic lymph nodes, and eight (2.8%) patients had both pelvic and aortic metastatic lymph nodes. Lymphovascular space invasion was associated with deep myometrial infiltration (PConclusionWe found that when lymphovascular space invasion score ≤4, there is a very low possibility of finding lymph nodal involvement. The preoperative lymphovascular space invasion score could complement the SLN algorithm to avoid unnecessary lymphadenectomies.

Introduction Vulvar cancer often requires radical vulvectomy with subsequent vulvar flap. Approximately in 20–60% of cases, there are post-operative complications ranging from infection to flap necrosis that often require reoperation. Several methods have been described to verify the vitality of the flap, but these are often expensive and require specific machinery that is not generally present in a gynecological clinic. In this case report, we present a viability verification of V Y fasciocutaneous advancement flap for vulvar reconstruction by Endoscopic Near-Infrared and Indocyanine Green. Methodology The patient was a 67-year-old woman with FIGO IB ≤ 4 cm squamous cell vulvar cancer with absence of inguinal lymphadenopathy. The lesion appeared about 35 mm from the lateral margin of the large left lip and extended to the left inguinocrural fold. The patient underwent left inguinal lymphadenectomy and left radical hemivulvectomy with a left fasciocutaneous medial-thigh advancement flap. For the flap evaluation, we endovenous administered 50 mg of Indocyanine Green diluted in 10 ml of saline solution. After 10 min we visualized the flap margin with a near-infrared laparoscopic view. The evaluation was repeated at the end of the surgical procedure and we confirmed the good vascularization of the flap. Results No early or late post-operative complications were obtained. There was no wound dehiscence, marginal necrosis or surgical site infection. Conclusions Verifying the viability of the vulvar flap using near-infrared laparoscopic optics was easy to use, reproducible and highly economical technique. This could be a reproducible alternative to other more expensive techniques.

Poly ADP -Ribose Polymerase (PARP) inhibitors (PARPi) were firstly licensed for maintenance treatment in recurrent, platinum-sensitive, platinum responsive epithelial ovarian cancer patients, harboring or not a BRCA mutation. Three new phase III trials - PAOLA1/ENGOT-OV25, PRIMA/ENGOT-OV26 and VELIA/GOG-3005 - showed that there is a role for PARPi also in first-line setting, as maintenance or in combination with platinum-based chemotherapy. Nevertheless the published trials raised several questions on what is the best treatment according to the molecular and clinical characteristics of the treated patients. This review focuses on the published data in order to inform clinician decision making on what could be the best sequence or combination of treatments for the three molecular defined cohorts of patients emerging in the first line trials (the carriers of a BRCA mutation (BRCAmut), those with a deficiency in homologous recombination system (HRd) and those with a proficient homologous recombination system (HRp)) and put the newly published data in the context of the ovarian cancer treatment landscape.

OBJECTIVE: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been recently reported with favorable oncological outcomes as treatment of advanced epithelial ovarian cancer (EOC). The aim of this study was to demonstrate the feasibility of CRS+HIPEC with cisplatin and paclitaxel for the treatment of advanced EOC. METHODS: This is a prospective observational study of 54 patients, from April 2007 to October 2013, with primary or recurrent peritoneal carcinomatosis due to EOC. The mean age was 54.51±9.34. Thirty patients (59%) had primary EOC, and 24 patients (41%) had recurrent disease. RESULTS: Mean peritoneal cancer index was 10.11 (range, 0 to 28), complete cytoreduction (CC0) was achieved for 47 patients (87%), CC1 for seven patients (13%). Patients with suboptimal cytoreduction (CC2 and CC3) were not included in the study. The mean stay in intensive care unit was 4.73±5.51 days and the mean hospitalization time was 24.0±10.03 days. We did not observe any intraoperative death. Seven patients (13%) required additional operations. Three patients (5.6%) died within 30 days from the procedure. Severe complications were seen in 19 patients (35.2%). During the follow-up period, disease recurred in 33 patients (61.1%); the median disease-free survival time was 12.46 months and the median overall survival time was 32.91 months. CONCLUSION: CRS+HIPEC with cisplatin and paclitaxel for advanced EOC is feasible with acceptable morbidity and mortality. Additional follow-up and further studies are needed to determine the effects of HIPEC on long term survival.