Role of V-Y flap reconstruction in vulvar cancer patients: multicenter retrospective study.

OBJECTIVE: To assess if the use of a V-Y reconstructive flap after excisional radical surgery positively influences the surgical outcomes in patients with vulvar cancer. METHODS: This was a multicenter, retrospective, controlled study. Surgical outcomes and complication rates of women with invasive vulvar cancer who underwent radical surgery and vulvar reconstruction and those who underwent radical surgery without the reconstruction step were compared. Only patients who underwent bilateral or unilateral V-Y advancement fascio-cutaneous flaps were included in the reconstruction group. Univariate and multivariate logistic regression models were used to analyze predicting variables for their association with complication rates. RESULTS: Overall, 361 patients were included: 190 (52%) underwent the reconstructive step after the excisional radical procedure and were compared with 171 (47.4%) who did not undergo the reconstructive step. At multivariate analysis, body mass index >30 kg/m2 (odds ratio (OR) 3.36, p=0.007) and diabetes (OR 2.62, p<0.022) were independently correlated with wound infection. Moreover, increasing age (OR 1.52, p=0.009), body mass index >30 kg/m2 (OR 3.21, p=0.002,) and International Federation of Gynecology and Obstetrics (FIGO) stages III-IV (OR 2.25, p=0.017) were independent predictors of wound dehiscence. A significant reduction in the incidence of postoperative wound complications among patients who underwent V-Y reconstructive flaps was demonstrated. This was correlated more significantly in women with lesions >4 cm. CONCLUSIONS: The adoption of V-Y flaps in vulvar surgery was correlated with reduced surgical related complications, particularly in vulnerable patients involving large surgical defects following excisional radical procedures.

It is time to implement molecular classification in endometrial cancer.

A huge effort has been done in redefining endometrial cancer (EC) risk classes in the last decade. However, known prognostic factors (FIGO staging and grading, biomolecular classification and ESMO-ESGO-ESTRO risk classes stratification) are not able to predict outcomes and especially recurrences. Biomolecular classification has helped in re-classifying patients for a more appropriate adjuvant treatment and clinical studies suggest that currently used molecular classification improves the risk assessment of women with EC, however, it does not clearly explain differences in recurrence profiles. Furthermore, a lack of evidence appears in EC guidelines. Here, we summarize the main concepts why molecular classification is not enough in the management of endometrial cancer, by highlighting some promising innovative examples in scientific literature studies with a clinical potential significant impact.

The role of L1CAM as predictor of poor prognosis in stage I endometrial cancer: a systematic review and meta-analysis.

INTRODUCTION: Molecular and genomic profiling in endometrial cancer is increasing popularity. L1 cell adhesion molecule (L1CAM) is frequently mutated in endometrial cancer. In this paper, we aim to evaluate the prognostic role of L1CAM in patients with stage I endometrial cancer. METHODS: We performed a systematic review and meta-analysis searching in PubMed (MEDLINE), EMBASE, and Web of Science database to identify studies reporting the expression of L1CAM in endometrial cancer. The primary endpoint measure was to assess and evaluate the impact of L1CAM on survival outcomes. This study was performed according to the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) statement. RESULTS: Five studies were included. The pooled results suggested that L1CAM expression influences survival outcomes in stage I endometrial cancer. High L1CAM expression correlated with worse disease-free survival (HR 4.11, 95% CI 1.02-16.59, p = 0.047) and overall survival (HR 3.62, 95% CI 1.32-9.31, p = 0.012). High L1CAM level was also associated with a more aggressive FIGO grade and with older age. CONCLUSION: This systematic review supported that L1CAM have a prognostic role in stage I endometrial cancer, thus providing a potential useful tool for tailoring the need of adjuvant therapy.

Ten-year outcomes following laparoscopic and open abdominal radical hysterectomy for "low-risk" early-stage cervical cancer: A propensity-score based analysis.

OBJECTIVE: Accumulating evidence suggested the detrimental effects of adopting minimally invasive surgery in the management of early-stage cervical cancer. However, long-term evidence on the role of minimally invasive radical hysterectomy in "low-risk" patients exists. METHODS: This is multi-institutional retrospective study comparing minimally invasive and open radical hysterectomy in low-risk early-stage cervical cancer patients. A propensity-score matching algorithm (1:2) was used to allocate patients into the study groups. Kaplan-Meir model was used to estimate 10-year progression-free and overall survival. RESULTS: Charts of 224 "low-risk" patients were retrieved. Overall, 50 patients undergoing radical hysterectomy were matched with 100 patients undergoing open radical hysterectomy. Minimally invasive radical hysterectomy was associated with a longer median operative time (224 (range, 100-310) vs. 184 (range, 150-240) minutes; p < 0.001), lower estimated blood loss (10 (10-100) vs. 200 (100-1000) ml, p < 0.001), and shorter length of hospital stay (3.8 (3-6) vs. 5.1 (4-12); p < 0.001). Surgical approach did not influence the risk of having intra-operative (4% vs. 1%; p = 0.257) and 90-day severe (grade 3+) postoperative complication rates (4% vs. 8%; p = 0.497). Ten-year disease-free survival was similar between groups (94% vs. 95%; p = 0.812; HR:1.195; 95%CI:0.275, 5.18). Ten-year overall survival was similar between groups (98% vs. 96%; p = 0.995; HR:0.994; 95%CI:0.182, 5.424). CONCLUSIONS: Our study appears to support emerging evidence suggesting that, for low-risk patients, laparoscopic radical hysterectomy does not result in worse 10-year outcomes compared to the open approach. However, further research is needed and open abdominal radical hysterectomy remains the standard treatment for cervical cancer patients.

Machine learning endometrial cancer risk prediction model: integrating guidelines of European Society for Medical Oncology with the tumor immune framework.

OBJECTIVE: Current prognostic factors for endometrial cancer are not sufficient to predict recurrence in early stages. Treatment choices are based on the prognostic factors included in the risk classes defined by the ESMO-ESGO-ESTRO (European Society for Medical Oncology-European Society of Gynaecological Oncology-European Society for Radiotherapy and Oncology) consensus conference with the new biomolecular classification based on POLE, TP53, and microsatellite instability status. However, a minority of early stage cases relapse regardless of their low risk profiles. Integration of the immune context status to existing molecular based models has not been fully evaluated. This study aims to investigate whether the integration of the immune landscape in the tumor microenvironment could improve clinical risk prediction models and allow better profiling of early stages. METHODS: Leveraging the potential of in silico deconvolution tools, we estimated the relative abundances of immune populations in public data and then applied feature selection methods to generate a machine learning based model for disease free survival probability prediction. RESULTS: We included information on International Federation of Gynecology and Obstetrics (FIGO) stage, tumor mutational burden, microsatellite instability, POLEmut status, interferon γ signature, and relative abundances of monocytes, natural killer cells, and CD4+T cells to build a relapse prediction model and obtained a balanced accuracy of 69%. We further identified two novel early stage profiles that undergo different pathways of recurrence. CONCLUSION: This study presents an extension of current prognostic factors for endometrial cancer by exploiting machine learning models and deconvolution techniques on available public biomolecular data. Prospective clinical trials are advisable to validate the early stage stratification.

Evaluation of Peri-Operative Management in Women with Deep Endometriosis Who are Candidates for Bowel Surgery: A Survey from the Italian Society of Gynecologic Endoscopy.

STUDY OBJECTIVE: There is great consensus that the implementation of the enhanced recovery after surgery (ERAS) approach is beneficial for surgical patients, but there is a paucity of data concerning its application in women with deep endometriosis (DE) who are candidates for bowel surgery. The survey described herein was aimed at gathering detailed information on perioperative management of DE patients who were undergoing sigmoid/rectal (discoid or segmental) resection within the Italian Society of Gynecologic Endoscopy (SEGI) group. DESIGN: Baseline survey. SETTING: National survey conducted within the main Italian cooperative group in minimally invasive gynecologic surgery (SEGI). PATIENTS: The study did not involve patients. INTERVENTIONS: A 63-item questionnaire covering ERAS items for gynecologic/elective colorectal surgery was sent to SEGI centers. Only questionnaires from centers that reported performing ≥10 sigmoid/rectal resections per year were considered for this analysis. MEASUREMENTS AND MAIN RESULTS: Thirty-three of 38 (86.8%) of the questionnaires were analyzed. The rates of concordance with the ERAS guidelines were 40.4%, 64.4%, and 62.6% for preoperative, intraoperative, and postoperative items, respectively. The proportion of overall agreement was 56.6%. Preoperative diet, fasting and bowel preparation, correction of anemia, avoidance of peritoneal drains, postoperative feeding, and early mobilization were the most controversial items. Comparative analysis revealed that the referred rates of complete disease removal and conversion to open surgery were significantly different depending on case volume (p = .044 and p = .003, respectively) and gynecologist's/surgeon's experience (p = .042 and p = .022, respectively), with higher chances of obtaining a complete laparoscopic/robotic excision of endometriosis in centers that reported ≥30 DE surgeries performed per year and/or ≥90% of bowel resections performed by a gynecologist/general surgeon specifically dedicated to DE management. In contrast, the rates of concordance with the ERAS guidelines were not significantly different according to case volume (p = .081) or gynecologist's/surgeon's experience (p = .294). CONCLUSION: This is the first study on DE conducted on a national scale. The current survey results revealed suboptimal compliance with the ERAS recommendations and underline the need to improve the quality of perioperative care in DE patients undergoing sigmoid/rectal resection. This study is a first step toward building a consistent, structured reporting platform for the SEGI units and facilitating wide implementation and standardization of the ERAS protocol for DE patients in Italy.

Anatomical distribution of sentinel lymph nodes in patients with endometrial cancer: a multicenter study.

OBJECTIVE: Sentinel lymph node (SLN) mapping represents the standard approach in uterine confined endometrial cancer patients. The aim of this study was to evaluate the anatomical distribution of SLNs and the most frequent locations of nodal metastasis. METHODS: This was an observational retrospective multicenter study involving eight high volume gynecologic cancer centers in Italy. We reviewed 1576 patients with a histologically confirmed diagnosis of endometrial cancer from September 2015 to June 2020. All patients underwent total hysterectomy with salpingo-ophorectomy and SLN mapping. RESULTS: A total of 3105 SLNs were mapped and removed, 2809 (90.5%) of these were bilateral and 296 (9.5%) unilateral. The overall detection rate was 93.4% (77.9% bilateral and 15.5% unilateral). The majority of SLNs (80%) and positive SLNs (77.8%) were found at the external iliac and obturator level in both endometrioid and non-endometrioid endometrial cancer. Negative SLNs were more frequent in patients with endometrioid compared with non-endometrioid cancer (91.9% vs 86.1%, p<0.0001). Older patients, a higher body mass index, and non-endometrioid histology were more likely to have 'no mapping' (p<0.0001). Univariate and multivariate analysis showed that higher body mass index and age at surgery were independent predictive factors of empty node packet and fat tissue (p=0.029 and p<0.01, respectively). CONCLUSION: The most frequent sites of SLNs and metastases were located in the pelvic area below the iliac vessel bifurcation. Our findings showed that older age, a higher body mass index, and non-endometrioid histology had a negative impact on mapping.

The giant steps in surgical downsizing toward a personalized treatment of vulvar cancer.

The present article aims to highlight the importance of changes of personalized surgical treatment for vulvar cancer. Current international literature regarding surgical treatment of vulvar cancer was evaluated. This included several studies and systematic reviews. Radical surgery approach, such as en bloc resection, was the first therapeutic option and the standard care for many years, even if burdened with a high complication rate and frequently disfiguring. Taussing and Way introduced radical vulvectomy approach with en bloc bilateral inguinal-femoral lymphadenectomy; modified radical vulvectomy was developed, with a wide radical excision of the primary tumor. The role of inguinofemoral lymphadenectomy (mono or bilateral) changed in the years too, particularly with the advent of SLN biopsy as minimally invasive surgical approach for lymph node staging, in patients with unifocal cancer <4 cm, without suspicious groin nodes. More personalized and conservative surgical approach, consisting of wide local or wide radical excisions, is necessary to reduce complications as lymphedema or sexual disfunction. The optimal surgical management of vulvar cancer needs to consider dimensions, staging, depth of invasion, presence of carcinoma at the surgical margins of resection and grading, with the goal of making the treatment as individualized as possible.

Percutaneous-assisted laparoscopy for ovarian tissue cryopreservation: a single-center experience.

PURPOSE: To compare surgical and post-operative outcomes of patients submitted to traditional laparoscopy and percutaneous-assisted laparoscopy for ovarian tissue explant for cryopreservation. METHODS: This is a single-center retrospective comparative study conducted in IRCCS "Regina Elena" National Cancer Institute of Rome. Patients submitted to laparoscopic excision of ovarian tissue, before starting chemotherapy were enrolled. We compared the classic laparoscopic approach vs percutaneous-assisted laparoscopy, using the Percuvance grasping forceps. RESULTS: Fifty-nine young oncologic women were enrolled; 38 underwent a conventional laparoscopy (LAP), 21 received a percutaneous laparoscopy (PERC). The baseline characteristics were similar in both groups, furthermore no differences were found in terms of peri-operative complications, median estimated blood loss (p = 0.4), operative time (p = 0.2), recovery times (p = 0.1), median time to chemotherapy (p = 0.7), median area of collected samples (p = 0.9). The postoperative pain evaluated by VAS-score, was significantly lower in the PERC group vs LAP group, both the day of surgery (range 0-4 vs 0-2; p = 0.02) and after 1 (range 0-3 vs 0-2; p = 0.002) and 2 days (range 0-3 vs 0-1; p = 0.0001). Moreover, better aesthetic results were detected in the PERC group, 2 months after surgery (median 9 vs 10, range 7-10 vs 9-10; p = 0.0001). CONCLUSIONS: Percutaneous-assisted laparoscopy has proven to be an effective and safe procedure for the excision of ovarian tissue for cryopreservation, in young oncologic patients that want to preserve their fertility. The percutaneous procedure appears superior to conventional laparoscopy in terms of aesthetic outcomes and post-operative pain reduction. CLINICAL TRIAL ID: NCT05134090, 24th Nov 2021, retrospectively registered.

Fertility-sparing treatment in advanced-stage serous borderline ovarian tumors. An analysis from the MITO14 study database.

OBJECTIVES: To evaluate oncological and reproductive outcomes of women undergoing fertility-sparing surgery (FSS) for stage II-III serous borderline ovarian tumors (BOTs). METHODS: A multi-institutional retrospective study was conducted within the MITO Group. RESULTS: A total of 91 patients were recruited. The median follow-up time from primary cytoreduction was 127 months (IQR range 91-179). Forty-nine patients (53.8%) experienced at least one recurrence (median time to first relapse 22 months, IQR range 9.5-57). At univariable analysis, significant predictors of relapse were: size of largest extra-ovarian lesion, peritoneal cancer index, completeness of cytoreduction, type of implants. After multivariable analysis, the size of extra-ovarian lesions and the presence of invasive implants resulted as the only independent predictors of recurrence. Median disease-free survival (DFS) was 96 months (95% CI, 24.6-167.3), while median disease-specific survival (DSS) was not reached. Twenty-nine patients (31.8%) attempted to conceive: 20 (68.9%) achieved at least one pregnancy and 18 (62%) gave birth to a healthy child. At the end of the observation period, 88 patients (96.7%) showed no evidence of disease, 2 (2.2%) were alive with disease, and 1 patient (1.1%) died from BOT. CONCLUSIONS: Despite the recurrence high rate, FSS provides good chances of reproductive success with no impact on DSS. The presence of invasive peritoneal implants affects the DFS but not DSS nor reproductive outcome. The risk of recurrence would not seem to be related to the ovarian preservation per se, but to the natural history of the initial peritoneal spread.

Is there any therapeutic role of pelvic and para-aortic lymphadenectomy in apparent early stage epithelial ovarian cancer?

OBJECTIVE: The therapeutic role of pelvic and para-aortic lymphadenectomy in surgical staging of apparent early-stage epithelial ovarian cancer (eEOC) is still under debate. The aim of this study was to evaluate the potential therapeutic role of systematic lymphadenectomy in patients with eEOC. METHODS: Multi-center retrospective cohort study, comparing women with apparent eEOC who underwent comprehensive bilateral pelvic and para-aortic lymphadenectomy (defined as ≥20 lymph nodes) versus patients receiving no lymphadenectomy or lymph node sampling, from 05/1985 to 12/2016. Patients with bulky nodes at CT-scan and those without complete intra-peritoneal surgical staging were excluded. Only patients who received at least 3 cycles of platinum-based adjuvant chemotherapy were included. RESULTS: Out of 2559 patients with FIGO stage IA-IIIA1 ovarian cancer, 639 (25.0%) met inclusion criteria. 360 (56.3%) underwent comprehensive lymphadenectomy, 150 (23.5%) lymph node sampling and 129 (20.2%) no lymphadenectomy. Patients who underwent comprehensive lymphadenectomy were younger (p < 0.001), experienced a higher number of severe post-operative complications (p = 0.008) and had a longer time to start chemotherapy (p = 0.034). There was no difference in intra-operative complications. Median follow-up was 63 months (range, 5-342). The 5-year disease-free survival (DFS) was 79.7% vs. 76.5% vs. 68.3% (p = 0.006), and 5-year overall survival (OS) was 92.3% vs. 94.5% vs. 89.8% (p = 0.165) in women who received comprehensive lymphadenectomy vs. lymph node sampling vs. no lymphadenectomy, respectively. Lymphadenectomy represented an independent factor for DFS improvement, HR 0.52 (95%CI 0.37-0.73) (p < 0.001). CONCLUSION: Pelvic and para-aortic lymphadenectomy in surgical staging of eEOC improves DFS for the price of increasing post-operative complications and time to chemotherapy but does not affect OS. Better understanding of tumor biology may help to identify those patients in whom lymphadenectomy should still play a role.

Palliative electrochemotherapy in primary or recurrent vulvar cancer.

OBJECTIVE: Since vulvar cancer is such a rare disease, the international experience with electrochemotherapy has been derived from only a few centers. The aim of this study was to evaluate clinical outcome and side effects profile with the use of electrochemotherapy in patients with primary or recurrent vulvar cancer. METHODS: Data were retrospectively collected from November 2017 to November 2019 in two major Italian oncologic institutes: Regina Elena Institute and Fondazione Policlinico Universitario Agostino Gemelli IRCCS. Electrochemotherapy was offered in a palliative setting to patients with a primary or recurrent vulvar cancer who were not candidates for surgery or any other treatment, because of poor performance status or previous delivered treatments. All patients underwent general anesthesia. Electrical pulses were delivered using a pulse generator. Intravenous bleomycin was administered in conjunction with electrochemotherapy. Follow-up examinations were performed at 1, 3, and 6 months. Primary endpoint was to assess the response rate of electrochemotherapy as palliative treatment in patients with vulvar cancer. RESULTS: A total of 15 patients were included in the study. Fourteen patients (93.3%) had a squamous cell carcinoma and one patient had vulvar carcinosarcoma. Ten patients (66.7 %) had a single lesion and 5 patients (33.3%) had multiple lesions. Median number of electrical pulses was 22 (range 3-42) and median operative time was 13 (range 7-20) min. No intra-procedure complications occurred. One patient had pneumonia during their post-operative stay. Overall response rate after 1 month was 80%. At the 3-month follow-up, 3 patients (20%) had disease progression, 3 patients (20%) had died from ongoing disease, 1 patient (6.7%) died for other reasons, whereas the other patients maintained their 1-month clinical response. A total of 8/13 patients (61.5%) were alive at 6-month follow-up, whereas 6/12 patients (50%) were alive at 1-year follow-up. CONCLUSIONS: Electrochemotherapy is a feasible, easy to perform, and reproducible procedure in patients with primary or recurrent vulvar cancer who are unable to undergo surgery. Survival after 1 year in this population was 50%. Electrochemotherapy may have a role in the management of vulvar cancer, especially as palliative treatment when other therapies are no longer applicable.

Sexual Function following Laparoscopic versus Transvaginal Closure of the Vaginal Vault after Laparoscopic Hysterectomy: Secondary Analysis of a Randomized Trial by the Italian Society of Gynecological Endoscopy Using a Validated Questionnaire.

STUDY OBJECTIVE: The effect of the different types of vaginal cuff closures on posthysterectomy sexual function has not been investigated in depth. We evaluated if there is a difference between transvaginal versus a laparoscopic closure after total laparoscopic hysterectomy (TLH) on female sexual function, using a validated questionnaire. DESIGN: Secondary analysis of a prospective randomized controlled trial. SETTING: Three academic research centers. PATIENTS: Women consenting to telephone interviews on their sexual life before and after undergoing TLH were included. INTERVENTIONS: Patients were randomly assigned to a laparoscopic or transvaginal approach for vaginal cuff closure at the end of TLH for benign indications. MEASUREMENTS AND MAIN RESULTS: A validated questionnaire (the Female Sexual Function Index [FSFI]) was used to explore sexuality before and after the operation. Of the 1408 patients enrolled in the primary study, 400 patients were asked to complete the questionnaire. Of them, 182 (41.4%) were eligible and accepted enrollment in the present analysis. No difference was found in terms of pre- and postoperative FSFI scores between groups. Patients with a low preoperative FSFI score (<26.55) had a significantly higher likelihood of having a postoperative sexual disorder (p <.001). Women who received bilateral adnexectomy before menopause and those with postoperative vaginal cuff hematoma had a significantly lower postoperative FSFI score (p = .001 and p = .04, respectively). After multivariable analysis, both variables maintained at least a tendency toward an association with a lower postoperative FSFI score (odds ratio, 2.696; 95% confidence interval, 1.010-7.194; p = 0.048 and p = 0.053; odds ratio, 13.2; 95% confidence interval, .966-180.5, respectively). CONCLUSION: Transvaginal and laparoscopic cuff closures after TLH have similar sexual postoperative outcomes. A patient with sexual problems before TLH is more likely to have a low FSFI score postoperatively. Premenopausal patients undergoing bilateral ovariectomy and those with postoperative vaginal cuff hematoma have a worse postoperative sexual life. (Clinicaltrials.gov, protocol number NCT02453165, registration date May 25, 2015.).

Hysteroscopic Evaluation of Endometrial Changes in Breast Cancer Women with or without Hormone Therapies: Results from a Large Multicenter Cohort Study.

STUDY OBJECTIVE: The primary aim of our study was to investigate the incidence of endometrial pathologies, especially endometrial cancer, in women with breast cancer treated with tamoxifen (TAM), aromatase inhibitors (AIs), or receiving no treatment (NT). The secondary aim was to identify, in this cohort, ultrasonographic findings that represent robust indications for hysteroscopy and endometrial biopsy, to avoid unnecessary second-level diagnostic procedures. DESIGN: Multicenter retrospective cohort study (Clinical Trial ID: NCT03898947). SETTING: Data were collected from different Italian centers: Regina Elena National Cancer Institute of Rome, Arbor Vitae Centre of Rome, Gaetano Martino University Hospital of Messina, and Villa Sofia-Cervello Hospital of Palermo. PATIENTS: We selected and consecutively included patients with a history of breast cancer who had undergone hysteroscopy for ultrasonographic or clinical indications between January 2007 and December 2016. INTERVENTIONS: Diagnostic hysteroscopy with endometrial biopsy or operative hysteroscopy, when clinically indicated. MEASUREMENTS AND MAIN RESULTS: A higher percentage of patients in the TAM and AI groups had a normal endometrium compared with those in the NT group, whereas the incidence of endometrial polyps was higher in the NT group than in the others; no significant differences were observed among the 3 groups for other benign conditions or for premalignant and malignant uterine diseases, such as endometrial atypical hyperplasia and adenocarcinoma. CONCLUSION: TAM treatment does not seem to be associated with a higher rate of endometrial cancer in women with breast cancer compared with women treated with AIs or NT.

Neoadjuvant Endocrine Therapy in Breast Cancer: Current Knowledge and Future Perspectives.

In locally advanced (LA) breast cancer (BC), neoadjuvant treatments have led to major achievements, which hold particular relevance in HER2-positive and triple-negative BC. Conversely, their role in hormone receptor positive (HR+), hormone epidermal growth factor 2 negative (HER2-) BC is still under debate, mainly due to the generally low rates of pathological complete response (pCR) and lower accuracy of pCR as predictors of long-term outcomes in this patient subset. While administration of neoadjuvant chemotherapy (NCT) in LA, HR+, HER2- BC patients is widely used in clinical practice, neoadjuvant endocrine therapy (NET) still retains an unfulfilled potential in the management of these subgroups, particularly in elderly and unfit patients. In addition, NET has gained a central role as a platform to test new drugs and predictive biomarkers in previously untreated patients. We herein present historical data regarding Tamoxifen and/or Aromatase Inhibitors and a debate on recent evidence regarding agents such as CDK4/6 and PI3K/mTOR inhibitors in the neoadjuvant setting. We also discuss key issues concerning the optimal treatment length, appropriate comparisons with NCT efficacy and use of NET in premenopausal patients.

Sentinel-node biopsy in early-stage ovarian cancer: preliminary results of a prospective multicentre study (SELLY).

BACKGROUND: Systematic paraaortic and bilateral pelvic lymphadenectomy is the standard of a comprehensive surgical staging in presumed early epithelial ovarian cancer, but no prospective randomized evidence suggests a possible therapeutic value. Moreover, this procedure is associated with potential severe morbidity. The Sentinel Lymph Nodes in Early-Stage Ovarian Cancer trial is a prospective study designed to test whether sentinel node detection can accurately predict nodal status in a cohort of women with early epithelial ovarian cancer. OBJECTIVES: We here present the results of the first part of the Sentinel Lymph Nodes in Early-Stage Ovarian Cancer trial, regarding the feasibility of the sentinel lymph node technique and the preliminary findings regarding its safety and accuracy. STUDY DESIGN: The Sentinel Lymph Nodes in Early-Stage Ovarian Cancer trial is a prospective, phase II, single-arm study included patients with presumed stages I-II epithelial ovarian cancer planned for immediate or delayed minimally invasive comprehensive staging. The ovarian pedicle is injected with 2 mL of a 1.25 mg/mL indocyanine green solution. The pelvic and lumboaortic retroperitoneum is then accessed and inspected to identify and remove sentinel nodes. After sentinel node procedure, staging is completed including systematic pelvic and paraaortic lymphadenectomy. Assuming a sensitivity of 98.5% in predicting positive sentinel lymph nodes at histology, a pathological lymph node prevalence of 14.2%, a precision of estimate (ie, the maximum marginal error) d = 5%, a type I error α = 0.05, a sample size of 160 patients is needed to test the general hypothesis. Here we present the preliminary results on the first 31 patients enrolled. RESULTS: Thirty-one patients were included. Sentinel node was identified in 21 patients (detection rate, 67.7%). The detection rate was significantly higher in women undergoing immediate vs delayed staging (88.9% vs 41.7%, P = .003). Four patients had positive nodes. In all the patients with lymphatic dissemination, a positive sentinel node was identified (sensitivity, 100%; false-negative rate, 0%; negative predictive value, 100%). One (3.2%) intra- and 2 (6.5%) postoperative grade I complications occurred. CONCLUSION: Our data show that the detection of sentinel node in early epithelial ovarian cancer is low when patients are submitted to delayed-staging surgery. However, sentinel node procedure is feasible and has the potential to provide reliable and useful information on nodal status and may allow the avoidance of systematic lymphadenectomy in the majority of patients.

Sentinel-node biopsy in early stage ovarian cancer: a prospective multicentre study (SELLY).

BACKGROUND: Systematic para-aortic and bilateral pelvic lymphadenectomy is included in the standard comprehensive surgical staging in presumed early epithelial ovarian cancer. No prospective randomized evidence suggests it has potential therapeutic value, and related morbidity is not negligible. PRIMARY OBJECTIVES: To assess sensitivity, safety, and feasibility of the sentinel lymph node technique in identifying the presence of lymph node metastases in patients with early stage epithelial ovarian cancer. STUDY HYPOTHESIS: Sentinel lymph node detection with indocyanine green can accurately predict nodal status in a cohort of women with early stage epithelial ovarian cancer. TRIAL DESIGN: The SELLY trial is a prospective phase II interventional multicenter study. MAJOR INCLUSION/EXCLUSION CRITERIA: Inclusion criteria: Eastern Cooperative Oncology Group 0-1, apparent International Federation of Gynecology and Obstetrics (FIGO) stage I-II, histologically proven epithelial ovarian cancer. EXCLUSION CRITERIA: evidence of carcinomatosis, mucinous only at definitive histology. ENDPOINTS: Primary endpoint is sensitivity (true positive rate). Secondary endpoints include safety (complications rate of the procedure) and feasibility. SAMPLE SIZE: Assuming a sensitivity of 98.5% in predicting positive sentinel lymph nodes at histology, a pathological lymph node prevalence of 14.2%, a precision of estimate (ie, the maximum marginal error) d=5%, and a type I error α=0.05, a sample size of 160 patients is needed to test the general hypothesis (ie, to answer whether sentinel lymph nodes identified with indocyanine green can accurately predict nodal status at histology of patients with apparently early epithelial ovarian cancer). Assuming a drop-out rate of 10%, a total of 176 patients will be enrolled in the study. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: The accrual should be completed by December 2020 and results should be presented by March 2021. TRIAL REGISTRATION: The trial is registered at clinicaltrials.gov (NCT03563781).

GLUT 1 receptor expression and circulating levels of fasting glucose in high grade serous ovarian cancer.

In recent years, the poorly remarkable goals achieved in terms of patients' important outcomes for ovarian cancer have fueled our interest toward the study of its metabolic roots. Within this research pipeline, we assessed the association between the expression of the glucose transporter GLUT1, as expressed at the tumor tissue level, and circulating pre-surgical levels of fasting glucose in a case series including data from 40 patients with high FIGO stage serous ovarian cancer. Patients who provided data to the current analysis were randomly selected from a larger cohort. To our purposes, the procedures related to serum and tissue collection, storage and biomarker assessment were highly standardized and centralized at the institutional laboratories. The GLUT1 antibody SPM498 SPRING (REF. E13810) was used at a 1:500 dilution in 2 µm slides. Staining for GLUT1 was observed at the cell membrane level in all the cases assessed, but strong staining was described in 29 (72.5%) of them. The agreement between the two independent reviewers was 100%. Strong GLUT1 staining was inversely associated with circulating levels of fasting glucose, with a particularly striking difference for patients in the lowest fasting glucose tertile (p = 0.044). These results support the biological plausibility of the association of interest. If confirmed in larger studies, our findings may help clarify the potentials of biomarkers related to energy metabolism in terms of prognosis definition, treatment assignment, and outcome interpretation for patients with high FIGO stage serous ovarian cancer.

Laparoscopic vs transvaginal cuff closure after total laparoscopic hysterectomy: a randomized trial by the Italian Society of Gynecologic Endoscopy.

BACKGROUND: Vaginal cuff dehiscence following hysterectomy is considered an infrequent but potentially devastating complication. Different possible techniques for cuff closure have been proposed to reduce this threatening adverse event. OBJECTIVE: The aim of the present randomized study was to compare laparoscopic and transvaginal suture of the vaginal vault at the end of a total laparoscopic hysterectomy, in terms of incidence of vaginal dehiscence and vaginal cuff complications. Factors associated with vaginal dehiscence were also analyzed. This article presents the results of the interim analysis of the trial. STUDY DESIGN: Patients undergoing total laparoscopic hysterectomy for benign indications were randomized at the time of colpotomy to receive vaginal closure through transvaginal vs laparoscopic approach using a 1:1 ratio. Allocation concealment was obtained using a password-protected randomization database. Monopolar energy for colpotomy was set at 60W. Vaginal closure was performed with a single-layer running braided and coated 0-polyglactin suture. In all cases an attempt was performed to include the posterior peritoneum in the suture. Laparoscopic knots were tied intracorporeally. All patients were scheduled for a postoperative follow-up visit 3 months after surgery, to detect possible vaginal cuff complications. Univariate and multivariable analyses were performed to identify independent predictors of vaginal cuff dehiscence after total laparoscopic hysterectomy. RESULTS: After enrollment of 1408 patients, a prespecified interim analysis was conducted. Thirteen (0.9%) women did not undergo the postoperative assessment and were excluded. Baseline characteristics of the 1395 patients included (695 in the transvaginal group and 700 in the laparoscopic group) were similar between groups. Patients in the transvaginal group had a significantly higher incidence of vaginal dehiscence (2.7% vs 1%; odds ratio, 2.78; 95% confidence interval, 1.16-6.63; P = .01) and of any cuff complication (9.8% vs 4.7%; odds ratio, 2.19; 95% confidence interval, 1.43-3.37; P = .0003). Based on these findings, the data monitoring committee recommended that the trial be terminated early. After multivariable analysis, transvaginal closure of the vault was independently associated with a higher incidence of vaginal dehiscence and any vaginal complication; premenopausal status and smoking habit were independently associated with a higher risk of dehiscence. CONCLUSION: Laparoscopic closure of the vaginal cuff at the end of total laparoscopic hysterectomy is associated with a significant reduction of vaginal dehiscence, any cuff complication, vaginal bleeding, vaginal cuff hematoma, postoperative infection, need for vaginal resuture, and reintervention.

The Patient and Observer Scar Assessment Scale to Evaluate the Cosmetic Outcomes of the Robotic Single-Site Hysterectomy in Endometrial Cancer.

OBJECTIVE: The objective of this study was to evaluate the cosmetic outcome of robotic single-site hysterectomy (RSSH) in early-stage endometrial cancer. METHODS: We prospectively collected patient demographics, operative times, complications, pathologic results, and length of stay on all patients who underwent RSSH for early-stage endometrial cancer. The Patient and Observer Scar Assessment Scale (POSAS) was used for the evaluation of the cosmetic outcome. RESULTS: Forty-five patients were included in our study from January 2012 to October 2015. The median age of patients was 63 years (range, 35-84 years), and the median body mass index was 26.5 kg/m (range, 18-39 kg/m). No laparoscopic/laparotomic conversion was registered. The median docking time, console time, and total operative time were 7 minutes (range, 4-14 minutes), 46 minutes (range, 20-100 minutes), and 90 minutes (range, 45-150 minutes), respectively. The median blood loss was 50 mL (range, 10-150 mL). Nine patients underwent pelvic lymphadenectomy, and the median number of pelvic lymph nodes was 13 (range, 10-32). The median time to discharge was 3 days (range, 2-6 days). No intraoperative complications occurred, whereas we did observe 1 early postoperative complication. The oncological outcome was directly comparable to the literature. Patients reported low pain scores and high satisfaction in terms of postoperative scarring. The POSAS scores confirmed excellent cosmetic outcome of RSSH. CONCLUSION: Robotic single-site hysterectomy provided an efficient option for gynecologic oncologic surgery. The POSAS revealed high objective and patient-evaluated outcome, and patients were highly satisfied with the overall outcome of the appearance of their scars.