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Objective: In the era of target therapy and personalized medicine, BRCA mutational status has a major influence on survival in ovarian cancer patients. Our aim is to verify if the poorer prognosis of elderly ovarian cancer patients can be related to the biology of the tumor beyond their own morbidities and/or suboptimal treatments., Methods: This is a retrospective single-institution study evaluating prognosis of patients with a diagnosis of ovarian cancer and known BRCA status. We collected clinical and surgical characteristics and the distribution of BRCA mutational status according to age groups., Results: 1840 patients were included in the analysis. The rate of BRCA mutated decreased over age-range from 49.7% in patients aged <50 years to 18.8% in ≥80 years old women. The prognostic role of BRCA status on survival is maintained when focusing on the elderly population, with improved Disease Free Survival (27.2 months vs 16.5 months for BRCA mutated and wild type respectively, p = 0.001) and Cancer Specific Survival (117.6 months vs 43.1 months for BRCA mutated and wild type respectively, p = 0.001) for BRCAmut compared to BRCAwt patients. In the multivariable analysis, among elderly women, upfront surgery and BRCA mutation are independent factors affecting survival., Conclusions: Elderly patients experiment a poorer prognosis due to multiple factors that include both their medical condition and comorbidities, under-treatment and most importantly disease characteristics. We found that beyond disparities, BRCA mutation is still the strongest independent prognostic factor affecting both the risk of recurrence and death due to disease., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Retrospective series have shown secondary cytoreductive surgery improves oncological outcomes in recurrent low-grade serous ovarian cancer. We aim to compare surgical procedures and complications between patients with low-grade and high-grade recurrent serous ovarian cancer., Methods: This retrospective single-institution study includes patients with recurrent low-grade and high-grade serous ovarian cancer undergoing surgery between January 2012 to December 2021. Patients were propensity matched 1:3 for residual tumor at first surgery, presence of ascites and performance status. Complexity of surgery and postoperative complications were analyzed., Results: A total of 116 patients undergoing secondary cytoreductive surgery were included with 29 patients (25%) having low-grade ovarian cancer. The median age of the patients was 54 years (range: 19-85) and 57 years (range: 29-78) in low-grade and high-grade ovarian cancer, respectively (p=0.13). Stages III/IV at diagnosis were more frequent in patients with high-grade ovarian cancers (p<0.001). Peritoneal involvement was higher in low-grade compared with high-grade ovarian cancer as shown by the higher rate of diaphragmatic (41.4% vs 21.8%, p=0.05), abdominal wall (41.4% vs 18.4%, p=0.02) and pelvic (51.7% vs 21.8%, p=0.01) peritonectomy. Multiple bowel resections were higher in low-grade ovarian cancer (24.1% vs 8.0%, p=0.04), while high-grade ovarian cancer had a higher rate of nodal recurrences (73.2%% vs 37.9%, p=0.03). Overall, surgical complexity was higher in low-grade ovarian cancer (58.6% vs 36.8%; p=0.05), with higher median estimated blood loss (400 vs 200 mL; p=0.01) compared with high-grade. Complete cytoreduction was achieved in 26 patients (89.7%) with low-grade and 84 (96.6%) with high-grade (p=0.16) ovarian cancer, with no significant differences in postoperative complications., Conclusions: Secondary cytoreductive surgery in low-grade serous ovarian cancer patients was associated with higher complexity, multiple bowel resections, and higher median estimated blood loss than in high-grade serous ovarian cancer. The comparable rate of postoperative complications suggests that secondary cytoreductive surgery in this group of patients is feasible in expert centers., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Study objective To assess the effects of a protective ventilation strategy during Trendelenburg pneumoperitoneum surgery on postoperative oxygenation., Designs: Parallel-group, randomized trial., Setting: Operating room of a university hospital, Italy., Patients: Morbidly obese patients undergoing Trendelenburg pneumoperitoneum gynaecological surgery., Interventions: Participants were randomized to standard (SV: tidal volume = 10 ml/kg of predicted body weight, PEEP = 5 cmH 2 O) or protective (PV: tidal volume = 6 ml/kg of predicted body weight, PEEP = 10 cmH 2 O, recruitment maneuvers) ventilation during anesthesia., Measurements: Primary outcome was PaO 2 /FiO 2 one hour after extubation. Secondary outcomes included day-1 PaO 2 /FiO 2 , day-2 respiratory function and intraoperative respiratory/lung mechanics, assessed through esophageal manometry, end-expiratory lung volume (EELV) measurement and pressure-volume curves., Main Results: Sixty patients were analyzed (31 in SV group, 29 in PV group). Median [IqR] tidal volume was 350 ml [300-360] in PV group and 525 [500-575] in SV group. Median PaO 2 /FiO 2 one hour after extubation was 280 mmHg [246-364] in PV group vs. 298 [250-343] in SV group (p = 0.64). Day-1 PaO 2 /FiO 2, day-2 forced vital capacity, FEV-1 and Tiffenau Index were not different between groups (all p > 0.10). Intraoperatively, 59% of patients showed complete airway closure during pneumoperitoneum, without difference between groups: median airway opening pressure was 17 cmH 2 O. In PV group, airway and transpulmonary driving pressure were lower (12 ± 5 cmH 2 O vs. 17 ± 7, p < 0.001; 9 ± 4 vs. 13 ± 7, p < 0.001), PaCO 2 and respiratory rate were higher (48 ± 8 mmHg vs. 42 ± 12, p < 0.001; 23 ± 5 breaths/min vs. 16 ± 4, p < 0.001). Intraoperative EELV was similar between PV and SV group (1193 ± 258 ml vs. 1207 ± 368, p = 0.80); ratio of tidal volume to EELV was lower in PV group (0.45 ± 0.12 vs. 0.32 ± 0.09, p < 0.001)., Conclusions: In obese patients undergoing Trendelenburg pneumoperitoneum surgery, PV did not improve postoperative oxygenation nor day-2 respiratory function. PV was associated with intraoperative respiratory mechanics indicating less injurious ventilation. The high prevalence of complete airway closure may have affected study results., Trial Registration: Prospectively registered on http://clinicaltrials.govNCT03157479 on May 17th, 2017., Competing Interests: Declaration of Competing Interest DLG has received payments for travel expenses by Getinge, personal fees by GE, Intersurgical, Fisher and Paykel and MSD. MA has received payments for Board participation from Maquet, Air Liquide and Chiesi. DLG and MA disclose a research grant by General Electric Healthcare. All other authors disclose no conflict of interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: Next-generation sequencing (NGS) analysis has become an essential tool for endometrial carcinoma management. Moreover, molecular-driven therapies play an increasingly remarkable role in the era of precision oncology. This study aims to determine the clinical relevance of NGS testing in endometrial carcinoma management by analyzing the clinical benefit of NGS-driven targeted therapies., Methods: A single-center retrospective study was conducted on 25 endometrial carcinoma patients who underwent Foundation Medicine CDx assay at Fondazione Policlinico Universitario Agostino Gemelli, IRCCS (Rome, Italy). Tumor samples were analyzed by Foundation One CDx. A descriptive analysis of tumor genome profiles was performed. Assessment of clinical benefit according to RECIST 1.1 criteria was analyzed for patients who received a tailored treatment according to actionable targets identified by NGS testing., Results: Out of 25 endometrial carcinoma patients, 11 received targeted therapy. One patient was excluded from the clinical benefit assessment because of COVID-19-related death 1 month after starting the treatment. Eight of the remaining 10 patients benefited from targeted therapies, with an overall clinical benefit rate of 80%. A targeted agent belonging to the PI3K pathway was given to seven patients, with evidence of three partial responses (42.9%), three stable diseases (42.9%), and one progressive disease (14.2%) according to RECIST 1.1 criteria. One complete response (33.3%), one stable disease (33.3%), and one progressive disease (33.3%) were observed in the three patients treated with poly(ADP-ribose) polymerase (PARP) inhibitors according to their homologous recombination deficiency (HRD) status., Conclusion: This study highlights the importance of characterizing the mutation profile of patient tumors through NGS. Our findings suggest a clinical benefit of using NGS-driven targeted therapies in endometrial carcinoma patients. However, this personalized approach could benefit the health system in terms of cost-effectiveness by reducing the costs of inappropriate, ineffective, and often expensive treatments., Competing Interests: Competing interests: VS was on the advisory board for AstraZeneca, Clovis, Tesaro, GSK, MSD, EISAI, Roche, and PharmaMar. GS was a consultant and received consulting fees from Johnson & Johnson, AstraZeneca–MSD, and Covidien AG – a Medtronic company; he was on the speakers bureau and received honoraria from Olympus Europa SE & CO. KG, Baxter Healthcare SA, Intuitive Surgical Inc, and GlaxoSmithKline S.p.A. DL had a consulting or advisory role for PharmaMar, AstraZeneca, Clovis Oncology, GlaxoSmithKline, MSD, Genmab, Amgen, Seattle Genetics, Immunogen, Merck Serono, Oncoinvest, Corcept Therapeutics, and Sutro Biopharma. She was on the speakers’ bureau for AstraZeneca, Clovis Oncology, GlaxoSmithKline, MSD, and PharmaMar. Institutional Research Funding: PharmaMar, Clovis Oncology, GlaxoSmithKline, MSD, AstraZeneca, Genmab, Seagen, Immunogen, Incyte, Novartis, and Roche. She had travel expenses paid for by Roche, PharmaMar, AstraZeneca, Clovis Oncology, and GlaxoSmithKline., (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To evaluate the role of different specific types of germline breast cancer susceptibility BRCA mutations on the age of onset of high grade serous ovarian cancer., Methods: This was a multicenter, international, retrospective cohort of 474 patients diagnosed with recurrent or newly diagnosed high grade serous ovarian cancer, with known germline mutations in BRCA1/2 genes, treated between January 2011 and December 2020 in three academic centers in Europe. Patients were classified into four groups related to the type of BRCA1/2 genes mutation: frameshift, missense, nonsense, and splicing. Data from patients with splicing mutations were removed from the analysis because of the small numbers. The other three groups were compared., Results: Excluding the 29 patients with a splicing mutation, 474 patients were enrolled: 309 (65.2%) with frameshift mutations, 102 (21.5%) with nonsense mutations, and 63 (13.3%) with missense mutations. The BRCA1 gene was affected in 324 (68.4%) cases, while BRCA2 was involved in 150 (31.6%) women (p=0.06). We found a difference of more than 5 years in the age of onset of high grade serous ovarian cancer between BRCA1 and BRCA2 patients (mean 53.3 years vs 58.4 years; p=0.001), with a mean age of 55.1 years. Patients with nonsense germline mutations had the youngest age of onset, while women with frameshift mutations had the oldest age of onset of high grade serous ovarian cancer (mean 52.2 years vs mean 55.9 years), both in the BRCA1 and BRCA2 subgroups. There was no statistically significant difference in age of onset between early and advanced groups (mean 55.8 years vs 55.0 years; p=0.55)., Conclusion: Different types of germline BRCA mutations could determine different ages for onset of high grade serous ovarian cancer. If confirmed in larger series, this finding might have a clinical impact, potentially leading to a more tailored approach for risk reducing surgery for the prevention of high grade serous ovarian cancer., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The benefit of surgery and maintenance treatment with PARP inhibitors (PARPi) has been clearly demonstrated in ovarian cancer. Also, the efficacy and safety of stereotactic body radiotherapy has been shown in patients with metastatic, persistent, and recurrent disease. The aim of this study is to evaluate the management of oligometastatic progression during PARPi maintenance treatment., Methods: This is an observational, retrospective, single-arm study conducted from June 2017 to December 2020 in patients with recurrent ovarian cancer with oligometastatic progression under PARPi maintenance treatment and receiving surgery or stereotactic body radiotherapy for such recurrence. PARPi treatment was continued until further progression of the disease. The primary objective of the study was the median prolongation of the treatment-free interval-p (without platinum) after local treatment., Results: A total of 186 patients with ovarian cancer were treated with PARPi at recurrence. Of these, 30 (16%) developed oligometastatic progression. The median age was 49.5 years (range 35-73). Olaparib, niraparib and rucaparib were administered to 33%, 60%, and 7% of patients, respectively. The median prolongation of the treatment-free interval-p of patients treated with surgery or stereotactic body radiotherapy was 6 and 10 months, respectively (p=0.53). The median treatment-free interval-p of patients treated with surgery or stereotactic body radiotherapy at the time of oligometastatic progression was 32 and 29 months, respectively (p=0.44). At the time of this publication, 50% of patients are still on treatment with PARPi following progression., Conclusions: Patients with recurrent ovarian cancer who have oligometastic progression during PARPi maintenance may continue to benefit from PARPi if combined with local treatment., Competing Interests: Competing interests: CM reports fees for advisory work from GSK, AstraZeneca, Pharmamar, and Clovis outside the submitted work. GS reports consulting fees or speaker fees from TESARO Bio Italy Srl, Clovis Oncology Italy Srl, Johnson & Johnson, AstraZeneca/MSD, Covidien AG, a Medtronic company, and from Baxter Healthcare SA outside the submitted work. AF reports consulting fees or speaker fees from Pharmamar, Johnson & Johnson, AstraZeneca/MSD and MSD Italia Srl outside the submitted work., (© IGCS and ESGO 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Endometrial cancer is the most common gynaecological tumour in developed countries. The overall rate of relapse has remained unchanged in recent decades. Recurrences occur in approximately 20% of endometrioid and 50% of non-endometrioid cases. The aim of this systematic review is to compare different therapeutic strategies in the treatment of endometrial cancer recurrence to evaluate their prognostic and curative effects based on site and type of recurrence., Methods: This systematic review of literature was conducted in accordance with the PRISMA guidelines. The study protocol was registered on PROSPERO (CRD42020154042). PubMed, Embase, Chocrane and Cinahl databases were searched from January 1995 to September 2021. Five retrospective studies were selected., Results: A total of 3571 studies were included in the initial search. Applying the screening criteria, 299 articles were considered eligible for full-text reading, of which, after applying the exclusion criteria, 4 studies were selected for the final analysis and included in the systematic review. No studies were included for a quantitative analysis. We divided the results according to the location of the recurrence: locoregional recurrence, abdominal recurrence and extra abdominal recurrence., Conclusion: the treatment of choice should be assessed according to the relapse location and to the presence of single or multiple lesions. A crucial role in the decision-making algorithm is also the type of adjuvant treatment received at the time of the first diagnosis.

Background: The integration of molecular features with clinicopathological findings in endometrial cancer classification seems to be able to significantly refine risk assessment. Nevertheless, clinical management remains challenging, and different therapeutic options are available for each class. Further prognostic characterization of the subgroups within each risk class could be helpful in the decision-making process., Methods: This study evaluated the role of the 2020 European Society of Gynaecological Oncology (ESGO)/European Society for Radiotherapy and Oncology (ESTRO)/European Society of Pathology (ESP) risk assessment system and the three prognostic profiles adopted in the PORTEC-4a trial in predicting disease-free and overall survival in a retrospective study cohort of patients with early-stage endometrial cancer. Patients were selected according to a 1:2 propensity score matching analysis. Moreover, the sequencing of 29 genes was undertaken for tumor samples., Results: The study included 137 patients. No differences in disease-free or overall survival at 5 years were observed among the 2020 ESGO/ESTRO/ESP risk classes without molecular features (p = .766 and p = .176, respectively). Once molecular features were integrated, the probability of overall survival was significantly different (p = .011). When the three prognostic profiles were applied, the probability of recurrence had a p value of .097, and significant differences were observed in overall survival (p = .004). Among patients experiencing recurrence, 17.6% showed mutations in BRCA1/2, RAD50, BRIP1, and XRCC2, whereas 22.5% had PD-L1-positive expression and an MUTYH mutation., Conclusions: Further stratification within each risk class according to the most relevant prognostic features could better define the prognosis of patients with early-stage endometrial cancer. Nearly half of the patients who experienced recurrence showed a targetable molecular alteration for which dedicated trials should be encouraged., (© 2022 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Objective: Evidence on micrometastases and isolated tumor cells as factors associated with non-vaginal recurrence in low- and intermediate-risk endometrial cancer is limited. The goal of our study was to investigate risk factors for non-vaginal recurrence in low- and intermediate-risk endometrial cancer., Methods: Records of all patients with endometrial cancer surgically managed at the Mayo Clinic before sentinel lymph node implementation (1999-2008) were reviewed. We identified all patients with endometrioid low-risk (International Federation of Gynecology and Obstetrics (FIGO) stage I, grade 1 or 2 with myometrial invasion <50% and negative peritoneal cytology) or intermediate-risk (FIGO stage I, grade 1 or 2 with myometrial invasion ≥50% or grade 3 with myometrial invasion <50% and negative peritoneal cytology) endometrial cancer at definitive pathology after pelvic and para-aortic lymph node assessment. All pelvic lymph nodes of patients with non-vaginal recurrence (any recurrence excluding isolated vaginal cuff recurrences) underwent ultrastaging., Results: Among 1303 women, we identified 321 patients with low-risk (n=236) or intermediate-risk (n=85) endometrial cancer (median age 65.4 years; 266 (82.9%) stage IA; 55 (17.1%) stage IB). Of the total of 321, 13 patients developed non-vaginal recurrence (Kaplan-Meier rate 4.7% by 60 months; 95% CI 2.1% to 7.2%): 11 hematogenous/peritoneal and two para-aortic and distant lymphatic. Myometrial invasion and lymphovascular space invasion were univariately associated with non-vaginal recurrence. In these patients, the original hematoxylin/eosin slides review confirmed all 646 pelvic and para-aortic removed lymph nodes as negative. The ultrastaging of 463 pelvic lymph nodes did not identify any occult metastases (prevalence 0%; 95% CI 0% to 22.8% considering 13 patients; 95% CI 0% to 0.8% considering 463 pelvic lymph nodes)., Conclusion: There were no occult metastases in pelvic lymph nodes of patients with low- or intermediate-risk endometrial cancer with non-vaginal recurrence. Myometrial invasion and lymphovascular space invasion appear to be associated with non-vaginal recurrence., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: The standard treatment for epithelial early stage ovarian cancer (eEOC) includes laparotomic surgical staging, according to ESGO-ESMO guidelines. In the last decade, many investigators have assessed the safety and feasibility of minimally invasive surgery (MIS) staging in properly selected patients. However, survival data related to different surgical approaches (open versus MIS) are extremely limited. The aim of this study is to analyze the long-term oncological outcomes in eEOC patients treated with MIS., Materials and Methods: This is a multicenter observational retrospective study conducted in two tertiary oncological centers. We selected all consecutive women who underwent a laparoscopic or robotic staging for eEOC., Results: From January 2008 to December 2016, 254 eEOC patients underwent a MIS staging (188 laparoscopic staging and 66 robotic staging). Overall, 18.1% of patients were upstaged due to pathological findings. A total of 203 (79.9%) patients received platinum-based adjuvant chemotherapy. After a median follow-up of 61 months (range 13-118), 39 (15.3%) patients experienced recurrence. The 5-years progression free survival (PFS) and overall survival rates were 84.0% and 93.8%, respectively. In the univariate analysis, favorable variables influencing PFS were young age (≤45 years), non-serous histotype, tumor grade 1-2, and FIGO stage IA/IB. In the multivariate analysis, only grade 3 was shown to keep its negative independent prognostic value (HR = 3.47; p = 0.004), whereas FIGO stage ≥ IC showed a trend toward significance (HR = 1.75; p = 0.099)., Conclusion: This retrospective study represents the longest follow-up of eEOC patients managed by MIS. The MIS is a valuable therapeutic option in appropriately selected patients, although a randomized controlled trial is needed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Introduction: There are no reliable blood biomarkers for monitoring endometrial cancer patients in the current clinical practice. Circulating tumor DNA (ctDNA) is emerging as a promising non-invasive method to measure tumor burden, define prognosis and monitor disease status in many solid cancers. In this pilot study, we investigated if unique tumor-specific DNA junctions can be used to detect ctDNA levels in patients with endometrial cancer., Methods: Chromosomal rearrangements in primary tumors of eleven patients with high-grade or advanced stage endometrial cancer were determined by whole-genome Mate-Pair sequencing. Identified unique tumor-specific junctions were evaluated in pre- and six-week post-surgery patient plasma using individualized quantitative polymerase chain reaction (qPCR) assays. The relationship between clinicopathological features and detection of ctDNA was investigated., Results: CtDNA was detected in 60% (6/10) of cases pre-surgery and in 27% (3/11) post-surgery. The detection of ctDNA pre-surgery was consistent with clinical indicators of aggressive disease such as advanced stage (80% - 4/5), lymphatic spread of disease (100% - 3/3), serous histology (80% - 4/5), deep myometrial invasion (100% - 3/3), lympho-vascular space invasion (75% - 3/4). All patients in which ctDNA was detected post-surgically had type II endometrial cancer., Discussion: This pilot study demonstrates the feasibility of using personalized tumor-specific junction panels for detecting ctDNA in the plasma of endometrial cancer patients. Larger studies and longer follow-up are needed to validate the potential association between pre-surgical ctDNA detection and the presence of cancers with aggressive pathologic tumor characteristics or advanced stage observed in this study., Competing Interests: The authors declare no competing financial interests.

Objective: To evaluate trends in outpatient versus inpatient hysterectomy for endometrial cancer and assess enabling factors, cost and safety., Methods: In this retrospective cohort study, patients aged 18 years or older who underwent hysterectomy for endometrial cancer between January 2008 and September 2015 were identified in the Premier Healthcare Database. The surgical approach for hysterectomy was classified as open/abdominal, vaginal, laparoscopic or robotic assisted. We described trends in surgical setting, perioperative costs and safety. The impact of patient, provider and hospital characteristics on outpatient migration was assessed using multivariate logistic regression., Results: We identified 41 246 patients who met inclusion criteria. During the time period studied, we observed a 41.3% shift from inpatient to outpatient hysterectomy (p<0.0001), an increase in robotic hysterectomy, and a decrease in abdominal hysterectomy. The robotic hysterectomy approach, more recent procedure (year), and mid-sized hospital were factors that enabled outpatient hysterectomies; while abdominal hysterectomy, older age, Medicare insurance, black ethnicity, higher number of comorbidities, and concomitant procedures were associated with an inpatient setting. The shift towards outpatient hysterectomy led to a $2500 savings per case during the study period, in parallel to the increased robotic hysterectomy rates (p<0.001). The post-discharge 30-day readmission and complications rate after outpatient hysterectomy remained stable at around 2%., Conclusions: A significant shift from inpatient to outpatient setting was observed for hysterectomies performed for endometrial cancer over time. Minimally invasive surgery, particularly the robotic approach, facilitated this migration, preserving clinical outcomes and leading to reduction in costs., Competing Interests: Competing interests: CS reports personal fees from Intuitive Surgical, outside the submitted work. YL is a full-time employee and stock holder of Intuitive Surgical., (© IGCS and ESGO 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The aim of this study is to analyze the prognostic role of lymph-vascular space invasion (LVSI), evaluated in a semi-quantitative fashion on prognosis of early stage, low risk endometrial cancer (EC)., Methods: We enrolled patients who underwent surgery for endometrial cancer between 2003 and 2018 in two referral cancer center. All patients had endometrioid EC, G1-G2, with myometrial invasion <50%, and no lymph-node involvement. LVSI was analyzed in a semi-quantitative way, according to a 3-tiered scoring system in absent, focal and substantial., Results: Among 524 patients, any positive LVSI was found in 57 patients (10.9%) with focal LVSI (n=35, 6.7%) and substantial LVSI (n=22, 4.2%). Substantial LVSI was associated to higher rate of G2 (p<0.001), myometrial infiltration (p=0.002) and greater tumor dimensions (p=0.014). Patients with substantial LVSI were more likely to receive adjuvant treatment (6.6% vs. 52.6%, p<0.001). The 5-year OS was 99.5% in patients with absent LVSI and 70.6% in those with substantial LVSI (p<0.001). The 5-year disease free survival (DFS) was 93.6% in patients with absent LVSI and 56.5% in those with substantial LVSI (p<0.001). The rate of distant failures increased from 1.8% for absent LVSI to 22.7% for substantial LVSI (p=0.002). In univariate analysis substantial LVSI was the strongest predictor of poor overall survival (hazard ratio [HR]=11.9, p=0.001). Multivariate analysis showed that substantial LVSI was an independent predictive factor of both recurrence (HR=5.88, p=0.001) and distant failure (HR=10.6, p=0.006)., Conclusions: Substantial LVSI represents the strongest independent risk factor for decreased survival and distant relapse, indicating a role for potential hematogenous dissemination., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2021. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

In patients undergoing debulking surgery for ovarian cancer (OC), bevacizumab-combined chemotherapy has been reported to be associated with an increased incidence of adverse events (AEs). Reports in the literature have noted the overall morbidity of bevacizumab to be between 3.7% and 9%. The aim of this study is to report uncommon and unusual manifestations of morbidity in surgical cases performed at our third level referral centers for gynecologic oncology. Additionally, we review the rare and severe bevacizumab-related complications that have been described in the literature. We defined as "extreme", the particularly rare and/or severe complications up to determining a life-threatening condition or death, which are related to the use of bevacizumab. A case-series of extreme complications registered at our institutions were reported. In addition, a literature search of the PubMed, MEDLINE and EMBASE electronic databases was performed for this review. The studies collected included: 8 randomized controlled trials (RCT) and 5 prospective observational, 1 prospective phase-IV, 10 prospective phase-II, 2 prospective phase-I, and 20 retrospective studies, as well as 9 case reports. Bevacizumab was administered as primary treatment in adjuvant and neo-adjuvant setting in 16 and 5 studies respectively, as treatment for recurrence in 36 trials, and for secondary cytoreductive surgery (SCS) in 3 studies. The overall population administered with bevacizumab numbered 7,096 women. Extreme complications were observed in 591 patients, with a morbidity rate of the 8.3%. Overall, central nervous system (CNS), cardiovascular, gastrointestinal (GI) and primary infectious complications were seen in 22 patients (0.3%), 261 patients (3.7%), 159 patients (2.2%), and 8 patients (0.13%), respectively. Hemorrhagic and wound complications occurred in 18 women (0.25%), and 112 women (1.6%), respectively. Extreme complications related to the use of bevacizumab are rare, and often go unrecognized. The recognition and immediate management of such rare and life-threatening complications in patients treated at third level referral centers could significantly improve patient survival., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-4448). LCT serves as an unpaid editorial board member of Annals of Translational Medicine from Mar 2020 to Feb 2022. The other authors have no conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)

Background: In the primary treatment of apparent uterine-confined endometrial carcinoma, pelvic ± para-aortic lymphadenectomy has been considered the standard of care. Although some retrospective data suggest that the sentinel lymph node algorithm without complete lymphadenectomy can be used without jeopardizing oncologic outcome, prospective data are lacking., Primary Objectives: To assess the 36 month incidence of pelvic/non-vaginal recurrence in women with pathologically confirmed stage I intermediate-risk endometrioid endometrial carcinoma who have bilateral negative pelvic sentinel lymph nodes., Study Hypothesis: We hypothesize that patients with stage I, intermediate-risk endometrioid endometrial carcinoma who have bilateral negative pelvic sentinel lymph nodes will demonstrate a pelvic/non-vaginal recurrence rate comparable to historical estimate of stage I, intermediate-risk endometrioid endometrial carcinoma patients (estimated 2.5%)., Trial Design: This prospective multicenter single-arm observational study will follow women with stage I, intermediate risk endometrioid endometrial adenocarcinoma who have undergone successful hysterectomy, bilateral salpingo-oophorectomy, and bilateral sentinel lymph node biopsies, for recurrence. All patients will undergo lymphatic mapping using indocynanine green and will either receive no adjuvant treatment or vaginal brachytherapy only. Patients will be followed for 36 months., Major Inclusion/exclusion Criteria: Patients will be enrolled in the study cohort if all the following criteria are met: (i) at time of surgery: hysterectomy with bilateral adnexectomy, and successful bilateral pelvic sentinel lymph node mapping; (ii) on final pathology: pathologic stage I, intermediate-risk endometrioid endometrial carcinoma (grade 1 or grade 2 with ≥50% myometrial invasion, or grade 3 with <50% myometrial invasion), negative pelvic peritoneal cytology, and bilateral sentinel lymph nodes negative for malignancy; (iii) recommended adjuvant treatment: vaginal brachytherapy or no adjuvant treatment., Primary Endpoint: Incidence of pelvic/non-vaginal recurrence at 36 months., Sample Size: 182 patients for study cohort ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Accrual will be completed in 2023 with results reported in 2026., Trial Registration: NCT04291612., Competing Interests: Competing interests: Dr Abu-Rustum reports the following, outside the submitted work: grant from Stryker/Novadaq (paid to institution); grant from Olympus (paid to institution); grant from GRAIL (paid to institution)., (© IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The role of the different types of adjuvant treatments in endometrial cancer with para-aortic node metastases is unclear. The aim of this study was to report oncologic outcomes after adjuvant therapy in patients with stage IIIC2 endometrial cancer., Methods: This retrospective single-institution study assessed patients with stage IIIC2 endometrial cancer who underwent primary surgery from January 1984 to December 2014. All patients had hysterectomy (±salpingo-oophorectomy) plus lymphadenectomy (para-aortic nodes, ±pelvic nodes). We included all patients with stage III endometrial cancer and documented para-aortic lymph node metastases (International Federation of Obstetrics and Gynecologists stage IIIC2). We excluded patients who did not provide consent, who had synchronous cancer, or who underwent neoadjuvant chemotherapy. Follow-up was restricted to the first 5 years post-operatively. Cox proportional hazards models, with age as the time scale, was used to evaluate associations of risk factors with disease-free survival and overall survival., Results: Among 105 patients with documented adjuvant therapy, external beam radiotherapy was administered to 25 patients (24%), chemotherapy to 24 (23%), and a combination (chemotherapy and external beam radiotherapy) to 56 (53%) patients. Most patients receiving chemotherapy and external beam radiotherapy (80%) had chemotherapy first. The majority of relapses had a distant component (31/46, 67%) and only one patient had an isolated para-aortic recurrence. Non-endometrioid subtypes had poorer disease-free survival (HR 2.57; 95% CI 1.38 to 4.78) and poorer overall survival (HR 2.00; 95% CI 1.09 to 3.65) compared with endometrioid. Among patients with endometrioid histology (n=60), chemotherapy and external beam radiotherapy improved disease-free survival (HR 0.22; 95% CI 0.07 to 0.71) and overall survival (HR 0.28; 95% CI 0.09 to 0.89) compared with chemotherapy or external beam radiotherapy alone. Combination therapy did not improve prognosis for patients with non-endometrioid histology (n=45)., Conclusions: In our cohort of patients with stage IIIC2 endometrioid endometrial cancer, those receiving chemotherapy and external beam radiotherapy had improved survival compared with patients receiving chemotherapy or external beam radiotherapy alone. However, the prognosis of patients with non-endometrioid endometrial cancer remained poor, regardless of the adjuvant therapy administered. Distant recurrences were the most common sites of failure., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The choice of adjuvant treatment for women with stage II endometrial cancer is challenging, given the known increase in morbidity with external beam radiation compared with vaginal brachytherapy, and the lack of consensus on its benefits. We summarized the evidence on survival and recurrence for stage II endometrial cancer, defined as cervical stromal invasion, after adjuvant postoperative external beam radiotherapy and vaginal brachytherapy., Methods: We searched the MEDLINE, EMBASE, CENTRAL, and Scopus databases from inception to January 2019 to identify studies that compared adjuvant postoperative external beam radiotherapy with or without vaginal brachytherapy and vaginal brachytherapy alone in stage II endometrial cancer. Our primary outcome was the locoregional recurrence rate, defined as recurrence in the pelvis or vagina. Secondary outcomes included the rate of recurrence at any site, distant recurrence rate, vaginal recurrence rate, pelvic recurrence rate, and 5 year overall survival. Study selection, assessment, and data abstraction were performed by an independent set of reviewers. Random effects models were used to synthesize quantitative data., Results: We included 15 cohort studies reporting data on 1070 women. Most women with stage II endometrial cancer (848/1070, 79.3%) were treated with external beam radiotherapy with or without vaginal brachytherapy. Subgroup analysis was stratified by whether >90% of the women included underwent pelvic lymph node assessment (sampling or full dissection). Locoregional recurrence (pelvic and vaginal recurrence) was significantly reduced with external beam radiotherapy with or without vaginal brachytherapy compared with vaginal brachytherapy alone (14 studies (n=1057); odds ratio (OR) 0.33 (95% confidence interval (CI) 0.16 to 0.68); I 2 =5%) regardless of pelvic lymph node assessment. Most women (81.8%) who recurred locoregionally had a least one uterine risk factor (grade 3 tumor, myometrial invasion >50%, or lymphovascular invasion). There was no difference in overall survival with external beam radiotherapy with or without vaginal brachytherapy compared with vaginal brachytherapy alone (five studies (n=463); OR 0.78 (95% CI 0.34 to 1.80); I 2 =48%)., Conclusions: External beam radiotherapy with or without vaginal brachytherapy decreased the locoregional recurrence threefold for stage II endometrial cancer, regardless of pelvic lymph node assessment. Most women who suffered recurrence locoregionally had a least one high risk factor. Vaginal brachytherapy alone may be sufficient therapy for node negative stage II endometrial cancer without uterine risk factors, while those with uterine risk factors should be considered for external beam radiotherapy with or without vaginal brachytherapy to improve locoregional control., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Traditional treatment failure in recurrent ovarian cancer remains a challenge for clinicians. Tumor genetic testing is a promising tool which has been proved able to identify sensitivity profiles in patients affected by cancers. This may be helpful in choosing targeted systemic treatments, aiming to overcome histology boundaries and to avoid unnecessary toxicity. We describe the case of a patient affected by recurrent high-grade serous ovarian cancer responsive to MEK-inhibitors, who had undergone multiple lines of therapy. To our knowledge, this is the first reported case of recurrent high-grade ovarian cancer showing remarkable clinical, radiologic and biochemical response to trametinib. This report suggests that trametinib could be effective in high-grade serous ovarian cancer, although most of promising scientific data on this molecule have focused on low-grade ovarian cancer. Molecular profiling has gradually become part of care for patients affected by recurrent ovarian cancer, however further randomized studies are needed to prove its efficacy in everyday clinical practice., Competing Interests: All authors declare they have nothing to disclose., (© 2020 The Authors.)

Objective: To examine the effect of robotic-assisted surgery implementation for treatment of endometrial cancer in the United States on 30-day clinical outcomes and costs., Methods: We retrospectively reviewed data of adult patients who underwent total hysterectomy for endometrial cancer in the US hospitals in Premier Healthcare Database between January 1, 2008 and September 30, 2015. We conducted trend analyses comparing the proportions of surgical approaches with the associated clinical outcomes and costs over the study period using Mann-Kendall tests. Clinical outcomes and costs of robotic-assisted surgery, laparoscopic and open surgery have been compared after propensity score 1:1 matching in the most recent 3 years (January 1, 2013-September 30, 2015)., Results: Of a total of 35,224 patients, use of robotic-assisted surgery increased from 9.48% to 56.82% while open surgery decreased from 70.4% to 28.1% over the study period. A 2.5% decrease in major complications (P < .001), a 2.9% decrease in minor complications (P = .001), and a 2.0% decrease 30-day readmissions (P = .001) was observed across all surgical approaches. Perioperative 30-day total cost slightly decreased from US $11,048 to US $10,322 (P = .08). Among propensity-score matched patients, robotic-assisted surgery was associated with shorter hospitalization than open surgery (median [interquartile range], 2.0 [2.0-3.0] vs 4.0 [3.0-6.0] days) and laparoscopic surgery (2.0 [2.0-3.0] vs 3.0 [2.0-4.0] days), fewer 30-day complications (20.1% vs 33.7%) (all P < .001), and comparable perioperative 30-day total costs (median [interquartile range], US $12,200 [US $9,509-US $16,341] vs US $12,018 [US $8,996-US $17,162]; P = .34) with open surgery., Conclusion: Robotic-assisted surgery facilitated the widespread diffusion of a minimally invasive approach nationally for endometrial cancer, with reduction of perioperative morbidity and no increase in overall treatment-related 30-day costs at national level., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Antiangiogenic chemotherapy is a common treatment option for patients with advanced ovarian cancer (OC) and has been proven to be effective and generally safe. Nevertheless, in rare cases, these drugs can give serious complications such as gastrointestinal perforations that can be even mortal or very difficult to treat and can heavily impact the clinical management. We present a rare case of bevacizumab-induced gastric perforation in a patient with advanced OC occurred during bevacizumab-including chemotherapy in an adjuvant setting. Surgical treatment was not possible due to the frailty of the clinical condition of the patient and the gastric perforation was successfully treated with endoscopic suturing., (© 2020 S. Karger AG, Basel.)

Objectives: It is unclear if sentinel lymph node biopsy is associated with improved surgical outcomes compared with lymphadenectomy in patients with endometrial cancer. In this study we aimed to compare peri-operative surgical outcomes and treatment-related morbidity in patients who underwent robotic-assisted sentinel lymph node biopsy versus systematic pelvic lymphadenectomy or hysterectomy alone for apparent early-stage endometrial cancer., Methods: Records were reviewed of consecutive patients with International Federation of Gynecology and Obstetrics stages I-III endometrial cancer undergoing robotic-assisted staging from January 1, 2009, through June 30, 2016. For the purpose of this analysis we focused on the actual patients who had sentinel node biopsy only (ie, excluding those who had an associated lymphadenectomy either for failed mapping or during the learning curve). We also excluded patients who had para-aortic lymph node dissection from the lymphadenectomy group. Perioperative and 30-day surgical outcomes were compared between patients who underwent sentinel lymph node assessment and those who had pelvic lymphadenectomy or hysterectomy alone, respectively. Inverse probability of treatment weighting derived from propensity scores was used to minimize allocation bias in the comparison of outcomes between groups., Results: A total of 621 patients were analyzed: 188 (30.3%) with sentinel lymph node biopsy, 198 (31.9%) with pelvic lymphadenectomy, and 235 (37.8%) with hysterectomy alone. Inverse probability of treatment weights analysis balanced for baseline characteristics (age, body mass index, American Society of Anesthesiologists score, Charlson co-morbidity index, parity, prior cesarean section, and previous abdominal operation) showed no significant differences in intra-operative and post-operative complications, re-admissions, and re-operations between the groups. Compared with pelvic lymphadenectomy, the sentinel lymph node biopsy group had a shorter mean operative time (138.0 vs 222.8 min, p<0.001) and less median blood loss (50 vs 100 mL, p<0.001). Sentinel lymph node biopsy also was not associated with worse morbidity compared with hysterectomy alone., Conclusions: Introduction of sentinel lymph node biopsy reduces operative times and improves peri-operative surgical outcomes of robotic-assisted staging for apparent early-stage endometrial cancer without worsening the morbidity of hysterectomy alone., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Study Objective: To assess the feasibility and efficacy of minimally invasive pelvic exenteration (MIPE) in a multi-institutional Italian case series of women with gynecologic cancer and a review of the literature., Design: Retrospective cohort study (Canadian Task Force classification II-2)., Setting: Three Italian university/teaching hospitals: "Agostino Gemelli" Foundation University Hospital in Rome, "ARNAS Civico Di Cristina Benfratelli" Hospital in Palermo, and "Maggiore della Carità" Hospital in Novara., Patients: We reviewed all consecutive cases with gynecologic malignancies in this multi-institutional setting recorded between March 2014 and June 2017. Women with primary or central recurrent/persistent gynecologic cancer considered suitable for exenterative surgery after multidisciplinary tumor board discussion were included. Clinicopathological, perioperative, and survival data were retrieved from the institutional electronic database (STAR center)., Interventions: All patients underwent total or anterior MIPE with a laparoscopic or robotic approach., Measurements and Main Results: Twenty-three patients underwent MIPE during the study period, including 12 (52.1%) by a laparoscopic approach and 11 (47.9%) by a robotic approach. All but 1 woman underwent MIPE for recurrent disease. The overall median operative time was 540 minutes (range, 310-720 minutes) with laparoscopy, slightly longer than with the robotic approach (p = .04). Median estimated blood loss was 400 mL (range, 200-600 mL). R0 resection was achieved in 17 of 23 patients (73.9%). There were no perioperative deaths. Early major postoperative complications occurred in 2 patients (8.7%). The median duration of hospitalization was 10 days (range, 6-33 days). With a median follow-up of 15 months, 11 patients (47.8%) developed recurrence. The median disease-free survival was 11 months (range, 5-18 months). To date, 155 MIPEs for gynecologic cancers have been reported in the literature. Among these, 12.6% had major postoperative complications, and overall postoperative mortality was 0.6%., Conclusion: MIPE is a feasible procedure with low rate of intraoperative and postoperative complications. Careful patient selection is crucial to balance perioperative risks and potential survival benefits and to achieve complete tumor resection., (Copyright © 2019 AAGL. Published by Elsevier Inc. All rights reserved.)

Objective: To identify predictors of unsuccessful sentinel lymph node (SLN) mapping in patients with apparent early-stage endometrial cancer (EC) undergoing surgical staging with cervical injection of indocyanine green and SLN biopsy., Methods: We retrospectively identified consecutive patients with EC with attempted SLN biopsy between June 2014 and June 2016 at our institution. Patients were grouped according to whether they had a successful procedure, defined as the bilateral identification of SLNs, or an unsuccessful procedure, defined as unilateral or no SLN mapping. Logistic regression was used to evaluate predictors of an unsuccessful procedure., Results: Among 327 patients included in the analysis, 256 (78.3%) had a successful procedure and 71 (21.7%) had an unsuccessful procedure (15.0% unilateral SLN mapping, 6.7% no mapping). The rate of successful procedure increased from 57.7% to 83.3% between the first and last quarters of the 2-year study period, which represented the learning curve for the technique. The mean (SD) operative time decreased from 164 (55) to 137 (37) minutes. By multivariable analysis, lysis of adhesions at the beginning of surgery (odds ratio, 3.07; 95% CI, 1.56-6.07) and the presence of enlarged lymph nodes (odds ratio, 4.69; 95% CI, 1.82-12.11) were independently associated with an unsuccessful procedure., Conclusions: Lysis of adhesions at the beginning of surgery and the presence of enlarged lymph nodes independently affect the bilateral detection of SLNs., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To identify predictors of extensive lymphatic dissemination and distant recurrences in node-positive endometrial cancer (EC)., Methods: Clinicopathologic data were collected of patients who had fully staged EC with at least 1 positive lymph node. Permanent sections of metastatic lymph nodes were reviewed; metastases were characterized according to size (≤2 mm and >2 mm) and location in the lymph node (intra- vs extracapsular). Risk of occurrence of multiple pelvic and para-aortic lymph node dissemination was calculated by combining risk factors identified at multivariate analysis., Results: Of 96 patients, 85 had positive pelvic nodes, of whom 71 (83.5%) had high-volume metastases. In the presence of both macrometastasis in the pelvic basin (odds ratio [OR], 13.42; [95% CI, 2.44-73.83]) and uterine serosal involvement of the tumor at final pathologic evaluation (OR, 11.84 [95% CI, 1.22-115.11]), multiple pelvic node dissemination occurred in 91.7% of cases (vs 7.7% in the absence of both). Concomitant presence of pelvic macrometastasis, lymphovascular space invasion (LVSI), and extracapsular invasion led to 85.7% occurrence of para-aortic involvement (vs 11.1% if no factors present). LVSI was independently associated with nonvaginal recurrences (hazard ratio, 2.62 [95% CI, 1.33-5.16])., Conclusions: Presence of high-volume metastases in the pelvic lymph nodes is associated with concomitant presence of multiple positive pelvic nodes, as well as para-aortic node involvement. LVSI is associated with both para-aortic node involvement and occurrence of nonvaginal relapses. In this era of sentinel lymph node mapping, these factors may help predict the extent of lymphatic dissemination in EC., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: This study aimed to determine the prevalence of occult pelvic lymph node metastasis in patients with endometrial cancer (EC) with isolated paraaortic dissemination who underwent pelvic and paraaortic lymphadenectomy., Methods: From 2004 to 2008, patients undergoing surgery for EC at our institution were prospectively treated according to a validated surgical algorithm relying on intraoperative frozen section. For the current study, we re-reviewed pathologic slides obtained at the time of diagnosis and performed ultrastaging of all negative pelvic lymph nodes to assess the prevalence of occult pelvic lymph node metastasis., Results: Of 466 patients at risk for lymphatic dissemination, 394 (84.5%) underwent both pelvic and paraaortic lymphadenectomy. Of them, 10 (2.5%) had isolated paraaortic metastasis. Pathologic review of hematoxylin-eosin-stained slides identified 1 patient with micrometastasis in 1 of 18 pelvic lymph nodes removed. Ultrastaging of 296 pelvic lymph nodes removed from the 9 other patients (median [range], 32 [20-50] nodes per patient) identified 2 additional cases (1 with micrometastasis and 1 with isolated tumor cells), for a total of 3/10 patients (30%) having occult pelvic dissemination., Conclusions: Ultrastaging and pathologic review of negative pelvic lymph nodes of patients with presumed isolated paraaortic metastasis can identify occult pelvic dissemination and reduce the prevalence of true isolated paraaortic disease. In the era of the sentinel lymph node (SLN) algorithm for EC staging, which incorporates ultrastaging of the SLNs removed, these findings demonstrate that use of the SLN algorithm can further mitigate the concern of missing cases of isolated paraaortic dissemination., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To identify women affected by recurrent ovarian cancer who benefit from secondary cytoreductive surgery (SCS), analyse their clinical and biological features and investigate the role of minimally invasive surgery (MIS) and hyperthermic intraperitoneal-based chemotherapy (HIPEC) in this subset of patients., Methods: This narrative review examines the data available from the updated literature. An electronic literature search was conducted in PubMed Medline databases for articles published from 1990 to 2018., Results: Retrospective studies and preliminary data from the AGO-Desktop III trial show that cytoreductive surgery is associated with improved post-relapse survival in patients with platinum-sensitive relapse, compared to chemotherapy alone. This benefit is more evident in patients treated with complete or optimal primary debulking surgery at referral centres, who did not receive bevacizumab in first-line chemotherapy, and who present a localized pattern of disease. MIS has been proven to be a favourable approach to achieve a complete secondary debulking, reducing peri- and postoperative comorbidities. The application of HIPEC to SCS is associated with an improvement in oncological outcomes by preliminary results., Conclusions: While waiting for the final results of the ongoing randomized controlled trials, SCS seems feasible and safe in selected patients with recurrent ovarian cancer. Recently, more attention has been focused on the biological features of ovarian tumours, such as BRCA status. Further studies and molecular research should be conducted to identify individualized and targeted therapies in the treatment of ovarian cancer recurrences.

Objective: To investigate whether patients' altered body composition (measured with bioimpedentiometry), due to a poor nutritional status, predicts the incidence of no residual disease at primary debulking and the risk of complications in patients with newly-diagnosed advanced epithelial ovarian cancer (EOC)., Methods: Data regarding patients with newly-diagnosed stage IIIC-IV EOC undergoing elective nutritional assessment between December 2016 and March 2017, were prospectively collected. Bioelectrical impedance analysis (BIA) with measurement of BIA-derived phase angle [PhA] at 50KHz, was accomplished. Only patients with disease which was considered resectable at staging laparoscopy were submitted to open primary cytoreduction. The rate of residual tumor (RT)=0 and the incidence of complications were assessed., Results: Seventy patients were included. Fifty-two of them were submitted to primary cytoreduction (74.3%) and 48 (68.6% of the entire cohort, 92.3% of those who underwent primary debulking) had RT=0 at the end of surgery. Median values of PhA were significantly lower in patients with RT>vs. =0 (4.7, range: 3.6-5.8 vs. 5.3, range: 4.2-6.8; p=0.001). Twenty-four (out of the 52 operated) patients (46.2%) developed at least one complication. PhA was significantly lower in patients with vs. without complications (5, range: 3.6-6.4, vs. 5.4, range 4.5-6.8; p=0.03). After multivariable analysis, Fagotti score and PhA were the only independent predictors of residual disease (OR:13.56; 95%CI:1.33-137.6; p=0.027 and 9.24; 1.16-73.43; p=0.036, respectively) and of any complication (OR:4.9;95%CI:1.17-20.6; p=0.03 and 7.27; 1.45-36.4; p=0.01, respectively)., Conclusions: Derangement of body composition (likely due to disease-related malnutrition) expressed as a low phase angle, is an independent predictor of residual disease and peri-operative complications at the time of upfront cytoreduction for advanced EOC., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background/aim: To report on morbidity and oncological outcomes in a consecutive series of gynecological malignancies involving the vascular district., Patients and Methods: We retrospectively evaluated a consecutive series between 1/2015 and 1/2017 with suspicious gynecological malignancies involving the vascular district. Peri-operative data and survival rates were computed., Results: Eight-hundred-four women with gynecological malignancies were admitted for major oncologic surgery during the study period, and among them, 50 cases (6.2%) showed vascular involvement. Twenty-seven and 23 patients were submitted to minor and major vascular procedures, respectively. R0 resection was achieved in 44 patients. There were no perioperative mortalities. Major postoperative complications occurred in 6 patients (12.0%). The 2-year disease free survival (DFS) was 67% if R0 resection was achieved. In patients with positive pathological margins (n=2), the 2-year DFS was 33%., Conclusion: Vascular procedures can be safely performed with a proper pre-operative planning and may not be an impediment to major gynecological oncological surgery., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: This paper presents results from the inaugural Scope of Practice Survey of Optometry Australia members conducted in October 2015. The survey gathered information related to confidence in detecting and diagnosing key ocular conditions, grading diabetic retinopathy, prescribing scheduled medicines, access to equipment, confidence using equipment, incidence of patients requiring therapeutic management, referral practices and services provided., Methods: The survey was developed, piloted, modified and administered to members of Optometry Australia (excluding student and retired members), who had a current email address. Results were collated and analysed using Microsoft Excel., Results: Of the 587 optometrists in clinical practice who responded, 254 (43 per cent) had therapeutic endorsement of registration. The majority of respondents practised in a major city or surrounding suburbs (63 per cent). Independent practice was the most frequently cited practice type (58 per cent). The estimated average number of patients seen in a week was 48; there was a steady decrease in the number of patients per week with increasing age, from 53 for optometrists in their 20s to 27 for optometrists aged over 70. There was very high confidence (over 93 per cent) in ability to grade diabetic retinopathy and diagnose a range of ocular conditions. Confidence in performance of more advanced techniques was higher for endorsed than non-endorsed optometrists. Approximately 12 per cent of patients required a Schedule 4 therapeutic prescription. The most frequently recommended over-the-counter medications were for dry eye for both endorsed and non-endorsed optometrists. The most frequently prescribed Schedule 4 medications were anti-inflammatories. The most challenging conditions to prescribe for were glaucoma, microbial keratitis and uveitis. Approximately one in six therapeutically endorsed optometrists reported unexpected side effects of medications they had prescribed., Conclusion: Information from the survey will guide Optometry Australia in the design of continuing professional development programs and other materials., (© 2017 Optometry Australia.)

Study Objective: To compare the feasibility and safety of the TELELAP ALF-X system and standard laparoscopy for total hysterectomy to treat patients with benign and early malignant gynecologic disease., Design: Single-institution retrospective case-control study (Canadian Task Force classification II-2)., Setting: Catholic University of the Sacred Heart, Rome, Italy., Patients: Between October 2013 and May 2015, 203 women underwent TELELAP-ALF X (group 1) or standard laparoscopic (group 2) total hysterectomy and were enrolled., Interventions: Total standard laparoscopy vs TELELAP ALF-X robot-assisted hysterectomy for benign and early malignant gynecologic disease., Measurements and Main Results: In group 1, the median age was 55 years (range, 40-79 years), median body mass index (BMI) was 25 kg/m(2) (range, 17-38 kg/m(2)), and 51 patients (58%) had undergone previous abdominal surgery. In the control group, the median age was 55 years (range, 34-90 years), median BMI was 25 kg/m(2) (range, 17-41 kg/m(2)), and 31 patients (27%) had previous abdominal surgery. The median operative time was 147 minutes (range, 58-320 minutes) in group 1 and 80 minutes (range, 22-300 minutes) in group 2 (p = .055). The median estimated blood loss was 57 mL (range, 0-600 mL) in group 1 and 99 mL (range, 0-400 mL) in group 2, with no significant differences between the 2 groups (p = .963). Procedures were successfully performed without conversion in 94.3% of cases in the group 1 and in all cases in group 2. Early postoperative pain was significantly lower in group 2., Conclusion: TELELAP ALF-X hysterectomy in patients with benign and early malignant gynecologic disease is feasible and safe, and can be considered a valid option for these patients., (Copyright © 2016 AAGL. Published by Elsevier Inc. All rights reserved.)

This review of the literature aims at assessing the safety and effectiveness of robotic versus laparoscopic surgery in benign and malignant gynecological diseases. Robotic-assisted laparoscopy is already widely used in the United States and Europe for the main gynecological procedure - hysterectomy - and has proved feasible and comfortable for other benign and malignant gynecological procedures. However, the clinical effectiveness and safety of robotic surgery compared with standard laparoscopy have not been undoubtedly established. We reviewed the literature by searching in the Ovid/MEDLINE, PubMed, Cochrane Library, and Google Scholar databases for all the articles published from January 1995 to September 2015. More rigorous experimental studies are needed, that compare robotic-assisted surgery and laparoscopic surgery for gynecological diseases. However, current data seem to encourage the use of minimally-invasive surgery to treat benign and malignant gynecological diseases.

Background: Some universities are looking to provide a more diverse range of clinical learning experiences through extended clinical placement programs. This approach will potentially have a significant impact on practitioners. The aim of this study was to conduct a national survey of optometrists to ascertain their perspectives on participating in extended clinical placement programs., Methods: Members of Optometry Australia were invited to participate in a survey conducted during June and July 2014., Results: A total of 268 practitioners participated (six per cent of registered Australian optometrists): 159 were predominantly employees or locums and 109 were owners or managers who identified as the key representative of a practice or organisation for the purpose of this survey. Almost two-thirds (65 per cent) of participants, who were employees or locums were supportive of extended clinical placement programs. Among this group, females were more likely to be supportive than males (p = 0.033). In comparison, just over one-third (34 per cent) of participants who were key decision-makers were supportive, with 30 per cent possibly supportive and 36 per cent not supportive. Among key decision-makers, males were more likely to be supportive (p = 0.009). The top three perceived advantages of supervising a student were: opportunity to mentor early career development, opportunity to give back to the profession and future recruitment. The top three perceived disadvantages were: burden on time, decrease in number of patients examined and burden on support staff. Suggested incentives for supervising students were credit for continuing professional development and financial remuneration., Conclusion: There appears to be moderate support for extended clinical placement programs; however, there are incentives that might engage a larger proportion of the profession in the future. These findings can inform the development of effective and sustainable clinical training programs for optometry students. Additionally, the findings might be used as evidence to seek Government support for clinical placement training in optometry., (© 2016 Optometry Australia.)

Background: The role of bevacizumab in metastatic breast cancer is controversial. Identification of predictive biomarkers could help to select patients who really benefit from it. We evaluated the association of angiogenesis-related gene polymorphisms with the treatment outcome of bevacizumab in metastatic breast cancer patients., Patients and Methods: eNOS-786T/C and -894G/T, IL-8-251T/A genomic polymorphisms were assessed in 31 metastatic breast cancer patients treated with bevacizumab plus chemotherapy in the first-line setting. Testing for association between each polymorphism and treatment outcome was performed., Results: Patients with IL-8 251 AA genotype showed a significantly lower progression-free survival in each combination comparison: "TT" vs "AA" (13 vs 8 months; p = 0.008); TT vs TA vs AA (13 vs 11 vs 8 months; p = 0.02); TT vs TA +AA (13 vs 11 months; p = 0.01); TT + TA vs AA (12 vs 8 months; p = 0.01) and a lower overall survival when compared with TT +TA genotype (26 vs 51 months, p = 0.04). Patients carrying eNOS 894 TT genotype showed a statistically significant lower progression-free survival than patients with GG genotype (11.5 vs 26.5 months; p = 0.04) with no differences in the overall survival. No association with response rate was found with any of the polymorphisms analyzed., Conclusion: These findings suggest that IL-8 251T/A and eNOS-894 G/T polymorphisms might have a role in predicting treatment outcome of bevacizumab in metastatic breast cancer. Our results are hypothesis generating and need to be confirmed in larger clinical trials.

Unlabelled: The ISP (Safe Insertion of PICCs) protocol: a bundle of 8 recommendations to minimize the complications related to the peripherally inserted central venous catheters (PICC)., Introduction: The insertion of a peripherally inserted central venous catheter (PICC) is not without risks., Aim: The Italian Group for the Study of Long-Term Central Venous Access Devices (GAVeCeLT) has developed a protocol (SIP: Safe Implantation of PICCs) with the aim of minimizing the risks which may be associated with the placement of PICCs., Methods: The protocol is based on recommendations available in the literature and on the main clinical practice guidelines., Results: The SIP protocol, a bundle of evidence-based recommendations, it is is easy to use, inexpensive, and cost-effective., Conclusions: If routinely used and carefully inplemented, it greatly reduces complications such as failure of venipuncture, accidental arterial puncture, damage of median nerve, infection and catheter related venous thrombosis.

Hydatidosis represents a form of helminthic zoonosis with a stronger medical, social and economic impact. It is endemic in some areas of the world including Mediterranean countries, and therefore Italy. The disease is often diagnosed in an advanced phase, due to the poor symptomatology in the early stages. The best treatment is surgery. Emergency surgery is similar to elective surgery, though in some cases is preferable only a drainage procedure until the stabilization of the genreal and local conditions of the patient allow a radical intervention. The Authors report on their five year experience of surgical treatment of compliated pulmonar hydatidosis pointing out that exeresis must be aimed at preserving pulmonar function as much as possible.

The Authors have conducted some research on the action of Sulpiride in animals which had been previously obliged to search into the gastric lesion caused by the compulsion. According to them above drug determines a reduction of the quantity of animals affected from gastric lesion and attenuates in other animals the entity of the gastric lesion.

The AA, report about the action explicate by the hyperbaric treatment on the evolution of the experimental peritonitises from hurt of the digestive tube. In their opinion the AA, a hyperbaric daily treatment of an hour at two ATA exercises a protection about evolution of the peritoneal syndrome.