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ObjectivesThe aim of this retrospective multicenter study was to investigate the extent, feasibility, and outcomes of minimally invasive surgery at the time of interval debulking surgery in different gynecological cancer centers.Methods/MaterialsIn December 2016, 20 gynecological cancer centers were contacted by e-mail, to participate in the INTERNATIONAL MISSION study. Seven centers confirmed and five were included, with a total of 127 patients diagnosed with advanced epithelial ovarian cancer after neoadjuvant chemotherapy and minimally invasive interval surgery. Only women with a minimum follow-up time of 6 months from interval surgery or any cancer-related event before 6 months were included in the survival analysis. Baseline characteristics, chemotherapy, and operative data were evaluated. Survival analysis was evaluated using the Kaplan–Meier method.Results All patients had optimal cytoreduction at the time of interval surgery: among them, 122 (96.1%) patients had no residual tumor. Median operative time was 225 min (range 60 – 600) and median estimated blood loss was 100 mL (range 70 – 1320). Median time to discharge was 2 days (1–33) and estimated median time to start chemotherapy was 20 days (range 15 – 60). Six (4.7%) patients experienced intraoperative complications, with one patient experiencing two serious complications (bowel and bladder injury at the same time). There were six (4.7%) patients with postoperative short-term complications: among them, three patients had severe complications. The conversion rate to laparotomy was 3.9 %. Median follow-up time was 37 months (range 7 – 86): 74 of 127 patients recurred (58.3%) and 31 (24.4%) patients died from disease. Median progression-free survival was 23 months and survival at 5 years was 52 % (95% CI: 35 to 67).ConclusionsMinimally invasive surgery may be considered for the management of patients with advanced ovarian cancer who have undergone neoadjuvant chemotherapy, when surgery is limited to low-complexity standard cytoreductive procedures.

Uterine carcinosarcomas (UCSs) are aggressive biphasic malignancies, with a carcinomatous/epithelial component and a sarcomatous/mesenchymal counterpart. The aim of this study was to evaluate the impact of the sarcomatous component (homologous vs heterologous) on the overall survival (OS) and progression-free survival (PFS). This is a multicenter observational retrospective study conducted in patients with stage I and II UCSs. Ninety-five women with histological diagnosis of early-stage UCSs were retrieved: 60 (63.2%) had tumors with homologous sarcomatous components, and 35 (36.8%) with heterologous. At univariate analysis, a stromal invasion ≥ 50%, the presence of clear cell, serous or undifferentiated carcinomatous component, the heterologous sarcomatous component and FIGO stage IB and II were shown to be variables with a statistically significant negative impact on PFS. Similarly, a depth of invasion ≥ 50%, the heterologous sarcomatous component and FIGO stage IB and II were statistically negative prognostic factors also concerning OS. At multivariate analysis, only the heterologous sarcomatous component was confirmed to be a statistically significant negative prognostic factor both on PFS (HR 2.362, 95% CI 1.207-4.623, p value = 0.012) and on OS (HR 1.950, 95% CI 1.032-3.684, p = 0.040). Carcinomatous and sarcomatous components both played a role in tumor progression and patients' survival. However, only the sarcomatous component retained a statistical significance at the multivariable model suggesting its preeminent prognostic role in early-stage UCSs.

In Western countries, ovarian cancer (OC) still represents the leading cause of gynecological cancer-related deaths, despite the remarkable gains in therapeutical options. Novel biomarkers of early diagnosis, prognosis definition and prediction of treatment outcomes are of pivotal importance. Prior studies have shown the potentials of micro-ribonucleic acids (miRNAs) as biomarkers for OC and other cancers. We focused on the prognostic and/or predictive potential of miRNAs in OC by conducting a comprehensive array profiling of miRNA expression levels in ovarian tissue samples from 17 non-neoplastic controls, and 60 tumor samples from OC patients treated at the Regina Elena National Cancer Institute (IRE). A set of 54 miRNAs with differential expression in tumor versus normal samples (T/N-deregulated) was identified in the IRE cohort and validated against data from the Cancer Genoma Atlas (TCGA) related to 563 OC patients and 8 non-neoplastic controls. The prognostic/predictive role of the selected 54 biomarkers was tested in reference to survival endpoints and platinum resistance (P-res). In the IRE cohort, downregulation of the 2 miRNA-signature including miR-99a-5p and miR-320a held a negative prognostic relevance, while upregulation of miR-224-5p was predictive of less favorable event free survival (EFS) and P-res. Data from the TCGA showed that downregulation of 5 miRNAs, i.e., miR-150, miR-30d, miR-342, miR-424, and miR-502, was associated with more favorable EFS and overall survival outcomes, while miR-200a upregulation was predictive of P-res. The 9 miRNAs globally identified were all included into a single biologic signature, which was tested in enrichment analysis using predicted/validated miRNA target genes, followed by network representation of the miRNA-mRNA interactions. Specific dysregulated microRNA sets in tumor tissue showed predictive/prognostic value in OC, and resulted in a promising biological signature for this disease.

Introduction/Background*Uterine carcinosarcomas (UCSs) are aggressive biphasic malignancies, with a high grade carcinomatous/epithelial component and a high grade sarcomatous/mesenchymal counterpart. Several studies identified the carcinomatous part as the main factor affecting the aggressive behaviour of UCSs. However, other studies reported that the sarcomatous component, especially the presence of heterologous elements, was associated with a worse prognosis. The prognostic ‘driving force’ is not completely clear for these kind of tumours. For this reason, the aim of our study was to evaluate the impact of the sarcomatous component (Homologous vs Heterologous) on the overall survival (OS) and progression-free survival (PFS).MethodologyThis is a multicenter observational retrospective study conducted in patients with stage I and II UCSs.Result(s)*Ninety-five women with histological diagnosis of early stage UCSs were retrieved: 60 (63.2%) had tumors with homologous sarcomatous components, and 35 (36.8%) with heterologous. Tumors with a sarcomatous heterologous component were significantly larger than the homologous (T ≥ 50 mm: 82.9% vs 51.7%, p-value=0.002) and presented more often lymph-vascular space invasion (62.9% vs 25.9% respectively in patients with heterologous and homologous component, p-value=0.001). At univariate analysis, a stromal invasion ≥ 50%, the presence of clear cell, serous or undifferentiated carcinomatous component, the heterologous sarcomatous component and the FIGO stage IB and II were shown to be variables with a statistically significant negative impact on PFS. Similarly, a depth of invasion ≥ 50%, the heterologous sarcomatous component and the FIGO stage IB and II were statistically negative prognostic factors also concerning OS. At multivariate analysis, only the heterologous sarcomatous component was confirmed to be a statistically significant negative prognostic factor both on PFS (HR 2.362, 95% CI 1.207-4.623, p-value=0.012) and on OS (HR 1.950, 95% CI 1.032-3.684, p=0.040).Conclusion*In conclusion, in our large series of UCSs, both carcinomatous and sarcomatous components played a role in tumor progression and patients’ survival. However, only the sarcomatous component retained a statistical significance at the multivariable model suggesting its preeminent prognostic role in early stage UCSs.

Introduction/Background*Endometrial cancer (EC) patients have a good prognosis at early stages, but for recurrent or metastatic EC the prognosis remains poor. EC treatments are related to known prognostic factors included in ESMO-ESGO-ESTRO risk classes classification, but they are not sufficient to predict outcomes or recurrence rate of early stages. To improve patient clinical management and allow personalized therapy a better characterization of risk classes in EC is needed. To fill this gap, we investigated EC immune escape processes, customized on the knowledge of maternal-fetal interface immune mechanisms, since the two processes share common pathways.MethodologyThis has been addressed by the identification of potential shared immune-based signatures between maternal-fetal interface and EC, such as those linked to lectin-type oxidized LDL receptor 1 (LOX-1) and NALP3 inflammasome, in order to achieve a potential immune score implementation to better characterize EC risk classes. The immunohistochemical assessment of LOX-1 and NALP3 was performed on formalin-fixed paraffin-embedded (FFPE) endometrial tissues.Result(s)*41 patients divided in 3 groups were enrolled: healthy endometrial tissue, endometrial hyperplasia and EC. We detected an increased expression of LOX-1, by immunohistochemistry (IHC), within the endometrial carcinoma tissues, a lower expression in cases of hyperplasia, to arrive to an absent staining in the healthy endometrial tissue (*p< 0.05, *Kruskal-Wallis followed by Mann-Whitney test). This grading is inverted in NALP3, which expression appears to be lower in EC (*p< 0.05). A proportional relationship between LOX-1 and NALP3 expression was demonstrated (p=0.006, Spearman test, confirmed through a linear regression test): increasing the expression of LOX-1, NALP3 decreases.Abstract 501 Figure 1Immunohistochemical staining on formalin-fixed paraffin-embedded samples of endometrical tissue showing expression of LOX-1 and NALP3 markersAbstract 501 Table 1Clinical and pathologic features of enrolled featuresConclusion*An increased LOX-1 and a decreased NALP3 expression seems be associated with EC progression. To identify patients at risk of developing EC from pre-cancerous lesions, by searching potential immune prognostic factors, such as LOX-1 and NALP3 on endometrial biopsy, could re-defy the actual EC risk classes through a potential ’immune score’ creation. Nevertheless, further studies are needed to define EC transcriptome immune-based signature. Furthermore, pathways detected by deciphering the immune changes linked to EC progression, could be potential target for immunotherapy.

Introduction/BackgroundPrimary vaginal leiomyosarcomas (LMS) are rare, recurrent tumours with an unknown etiology; the prognosis is poor and there is no consensus guideline on their management. A nodular, 25 x 23 x 28 mm-mass, infiltrating the urethra but not the rectovaginal septum, was found in a 58-year-old previously hysterectomized woman. A biopsy showed a LMS of the vagina and an anterior pelvic exenteration was performed.MethodologyThe sample was fixed and prepared for light microscopy, transmission and scanning electron microscopy. An immunohistochemical analysis was performed.ResultsThe results confirmed a LMS of the vagina that was positive for vimentin, alpha-smooth muscle actin, caldesmon, desmin, p16 and p53. Light microscopy revealed that the mass contained a storiform pattern of spindle-shaped cells with blunt-ended nuclei. Cells were arranged in interwoven fascicles within a dense and richly vascularised stroma, suggesting an active neoangiogenesis. The histopathological analysis revealed a coagulative focal necrosis and low to moderate mitotic indexes, about 1–4/10 high power fields (HPF). Scanning Electron Microscopy (SEM) evidenced a dense collagenous stroma with numerous small blood vessels. Transmission Electron Microscopy (TEM) showed invasive neoplastic and pleomorphic cells with complex labyrinthic cytoplasm projections. Tumoral cells contained paranuclear crowds of dilated mitochondria, free ribosomes and a well-developed rough endoplasmic reticulum. There were atypical mitotic figures. Blood vessels were usually lined by a high and reactive endothelium.ConclusionThe histopathological and ultrastructural analyses confirmed the malignancy of this tumor. Best outcomes occur when the tumour is small, localized, and can be removed surgically with wide, clear margins, as in this case. As there are different kinds of malignant mesenchymal tumours, biopsy followed by immunohistochemistry and electron microscopy still represents a good diagnostic choice.DisclosureNothing to disclose

Introduction/BackgroundEndometrial cancer (EC) is mostly diagnosed at an early stage with a favorable overall survival. 5-year survival decreases from 95% for localized disease to less than 20% for metastatic disease. Survival is related to known prognostic factors. Nevertheless, they are not sufficient to predict either outcome or recurrence rate/site: to decipher the underlying aberrant biomolecular pathways seems to be promising, although it is not yet applicable in a clinical setting. In that purpose, to investigate EC recurrence patterns according to ESMO-ESGO-ESTRO risk classes, could be beneficial for an early recurrences detection and treatment with a survival rate improvement.Methodology758 women diagnosed with EC, and a 5-years follow-up, were enrolled: they were divided into the ESMO-ESGO-ESTRO risk classes (low LR, intermediate IR, intermediate-high I-HR, and high risk HR) and surgically treated as recommended, followed by adjuvant therapy, when appropriated.ResultsRecurrences were detected in 19,5%. Higher recurrence rate (RR) was significantly detected (p<0,001) in the HR group (40,3%) compared to LR (9,6%), IR (16,7%) and I-HR (17,1%). Recurrences were detected more frequently at distant sites (64%) compared to pelvic (25,3%) and lymph nodes (10,7%) recurrences (p<0,0001): this trend was evident in all risk classes except for the LR group, where no differences were detected between local and distant recurrences. 5-year distant-free (LR 99%, IR 94%, I-HR 86%, HR 88%) and local-free survivals (LR 99%, IR 100%, I-HR 98%, HR 95%) significantly differ between groups (p<0,0001 and p=0,003, respectively), even when we stratified according to adjuvant therapy (AT) approach. AT did not modify RRs in all risk classes, except for LR group (p=0,01) (85,71% of recurrences occur if no AT was administered).ConclusionThese results strengthen the need to identify biological factors to stratify patients at higher risk of relapse, independently or in addition to their risk class prognosis and current surgical and clinical managements.DisclosureNothing to disclose.

Introduction/BackgroundThe majority of women who undergo radical hysterectomy for endometrial cancer (EC) are obese and they may benefit from robotic surgery. The aim of this study is to compare robotic single-site hysterectomies (RSSH) and robotic multiport hysterectomies (RMPH) for EC in obese patients.MethodologyThis study compares RSSH with RMPH in obese patients with EC and FIGO stage I or II. Data were collected from July 2010 to October 2018 in four Italian institutes: Regina Elena National Cancer Institute of Rome, Fondazione Policlinico San Matteo and University of Pavia, Santa Chiara Hospital of Trento and University of Pisa. According to their BMI, patients were divided in 3 classes: A from 30 to 34.9 kg/m2, B from 35 to 39.9 kg/m2 and C 40 kg/m2 or higher.ResultsWe included 225 patients: 76 in the RSSH group divided, respectively, in 53, 18 and 5 in the A, B and C classes; 149 in the RMPH group divided, respectively, in 76, 37 and 36 in the A, B and C classes. In the RSSH group, the median operation time (OT) and blood loss (BL) were, respectively, 139 min and 50 ml in the A class, 142.5 min and 50 ml in the B class and 165 min and 100 ml in the class C. In the RMPH group, the median OT and the median BL were, respectively, 195 min and 100 ml in the class A, 170 min and 50 ml in the class B and 122.5 min and 75 ml in the class C. The conversion rate increased in the 3 classes, especially in the RSSH group (in the A, B and C classes, respectively, 1.8%, 5.5% and 60%).ConclusionTechnical difficulties in single-site surgery increase with the patients‘ BMI and when the BMI is 40 kg/m2 or higher this technique is most of the times unfeasible.DisclosureNothing to disclose.

Radical hysterectomy and plus pelvic node dissection are the primary methods of treatment for patients with early stage cervical cancer. During the last decade, growing evidence has supported the adoption of a minimally invasive approach. Retrospective data suggested that minimally invasive surgery improves perioperative outcomes, without neglecting long-term oncologic outcomes. In 2018, the guidelines from the European Society of Gynaecological Oncology stated that a “minimally invasive approach is favored” in comparison with open surgery. However, the phase III, randomized Laparoscopic Approach to Cervical Cancer (LACC) trial questioned the safety of the minimally invasive approach. The LACC trial highlighted that the execution of minimally invasive radical hysterectomy correlates with an increased risk of recurrence and death. After its publication, other retrospective studies investigated this issue, with differing results. Recent evidence suggested that robotic-assisted surgery is not associated with an increased risk of worse oncologic outcomes. The phase III randomized Robotic-assisted Approach to Cervical Cancer (RACC) and the Robotic Versus Open Hysterectomy Surgery in Cervix Cancer (ROCC) trials will clarify the pros and cons of performing a robotic-assisted radical hysterectomy (with tumor containment before colpotomy) in early stage cervical cancer.

The aim of our study was to investigate the role of the excised vaginal cuff length as a prognostic factor in terms of DFS and recurrence rate/site, in low-risk endometrial cancer (EC) patients. Moreover, we correlated the recurrence with the expression of L1CAM. From March 2001 to November 2016, a retrospective data collection was conducted of women undergoing surgical treatment for low-risk EC according to ESMO-ESGO-ESTRO consensus guidelines. Patients were divided into three groups according to their vaginal cuff length: V0 without vaginal cuff, V1 with a vaginal cuff shorter than 1.5 cm and V2 with a vaginal cuff longer than or equal to 1.5 cm. 344 patients were included in the study: 100 in the V0 group, 179 in the V1 group and 65 in the V2 group. The total recurrence rate was 6.1%: the number of patients with recurrence was 8 (8%), 10 (5.6%) and 3 (4.6%), in the V0, V1 and V2 group, respectively. No statistically significant difference was found in the recurrence rate among the three groups. Although the DFS was higher in the V2 group, the result was not significant. L1CAM was positive in 71.4% of recurrences and in 82% of the distant recurrences. The rate of recurrence in patients with EC at low risk of recurrence does not decrease as the length of the vaginal cuff removed increases. Furthermore, the size of the removed vaginal cuff does not affect either the site of recurrence or the likelihood of survival.