"From the tip to the deep of the iceberg": Parametrial involvement in endometriosis.

Deep endometriosis (DE) can be localized in the parametrium, a complex bilateral anatomical structure, sometimes necessitating intricate surgical intervention due to the potential involvement of autonomic nerves, uterine artery, and ureter. If endometriotic ovarian cysts have been considered metaphorically representative of "the tip of the iceberg" concerning concealed DE lesions, it is reasonable to assert that parametrial lesions should be construed as the most profound region of this iceberg. Also, based on a subdual clinical presentation, a comprehensive diagnostic parametrial evaluation becomes imperative to strategize optimal management for patients with suspected DE. Recently, the ULTRAPARAMETRENDO studies aimed to evaluate the role of transvaginal ultrasound for parametrial endometriosis, showing distinctive features, such as a mild hypoechoic appearance, starry morphology, irregular margins, and limited vascularization. The impact of medical therapy on parametrial lesions has not been described in the current literature, primarily due to the lack of adequate detection at imaging. The extension of DE into the parametrium poses significant challenges during the surgical approach, thereby increasing the risk of intra- and postoperative complications, mainly if performed by centers with low expertise and following multiple surgical procedures where parametrial involvement has gone unrecognized. Over time, the principles of nerve-sparing surgery have been incorporated into the surgical DE treatment to minimize iatrogenic damage and potentially reduce the risk of functional complications.

A review of phase II and III drugs for the treatment and management of endometriosis.

INTRODUCTION: Endometriosis is an estrogen-dependent disease that gives rise to pelvic pain and infertility. Although estroprogestins and progestins currently stand as the first-line treatments for this condition, demonstrating efficacy in two-thirds of patients, a significant portion of individuals experience only partial relief or symptom recurrence following the cessation of these therapies. The coexistence of superficial, deep endometriosis, and ovarian endometriomas, as three distinct phenotypes with unique pathogenetic and molecular characteristics, may elucidate the current heterogeneous biological response to available therapy. AREAS COVERED: The objective of this review is to furnish the reader with a comprehensive summary pertaining to phase II-III hormonal treatments for endometriosis. EXPERT OPINION: Ongoing research endeavors are directed toward the development of novel hormonal options for this benign yet debilitating disease. Among them, oral GnRH antagonists emerge as a noteworthy option, furnishing rapid therapeutic onset without an initial flare-up; these drugs facilitate partial or complete estrogen suppression, and promote prompt ovarian function recovery upon discontinuation, effectively surmounting the limitations associated with previously employed GnRH agonists. Limited evidence supports the use of selective estrogen and progesterone receptor modulators. Consequently, further extensive clinical research is imperative to garner a more profound understanding of innovative targets for novel hormonal options.

Current Medical Therapy for Adenomyosis: From Bench to Bedside.

Adenomyosis, characterized by the growth of endometrial tissue within the uterine wall, poses significant challenges in treatment. The literature primarily focuses on managing abnormal uterine bleeding (AUB) and dysmenorrhea, the main symptoms of adenomyosis. Nonsteroidal anti-inflammatory drugs (NSAIDs) and tranexamic acid provide limited support for mild symptoms or symptom re-exacerbation during hormone therapy. The levonorgestrel-releasing intrauterine system (LNG-IUS) is commonly employed in adenomyosis management, showing promise in symptom improvement and reducing uterine size, despite the lack of standardized guidelines. Dienogest (DNG) also exhibits potential benefits, but limited evidence hinders treatment recommendations. Danazol, while effective, is limited by androgenic side effects. Combined oral contraceptives (COCs) may be less effective than progestins but can be considered for contraception in young patients. Gonadotropin-releasing hormone (GnRH) agonists effectively manage symptoms but induce menopausal symptoms with prolonged use. GnRH antagonists are a recent option requiring further investigation. Aromatase inhibitors (AIs) show promise in alleviating AUB and pelvic pain, but their safety necessitates exploration and limited use within trials for refractory patients. This review highlights the complexity of diagnosing adenomyosis, its coexistence with endometriosis and uterine leiomyomas, and its impact on fertility and quality of life, complicating treatment decisions. It emphasizes the need for research on guidelines for medical management, fertility outcomes, long-term effects of therapies, and exploration of new investigational targets. Future research should optimize therapeutic strategies, expand our understanding of adenomyosis and its management, and establish evidence-based guidelines to improve patient outcomes and quality of life.

Rituximab for endometriosis: Unlikely translatability from oncology due to safety concerns?

This letter discusses the article "The Effects of Rituximab on Experimental Endometriosis Model in Rats" by Dogan et al., which evaluated the potential therapeutic efficacy of rituximab in an experimental animal model of endometriosis. While the study showed promising results in decreasing the volume of endometriotic implants and differences in B-cell count and fibrosis score, rituximab is typically used as a therapy for B lymphocyte malignancies and has potential short-term and long-term side effects. Additionally, animal models for endometriosis have limitations, and novel models are still being developed. Therefore, further preclinical research is necessary to evaluate the safety and efficacy of rituximab as a potential treatment for endometriosis in humans.

Microbiota Ecosystem in Recurrent Cystitis and the Immunological Microenvironment of Urothelium.

Urinary tract infections (UTIs) represent one of the most frequent low genital tract diseases in the female population. When UTIs occur with a frequency of at least three times per year or two times in the last six month, we speak of recurrent UTI (rUTI) and up to 70% of women will have rUTI within 1 year. It was previously thought that antibiotic resistance was principally responsible for the recurrence of UTIs, but nowadays new diagnostic technologies have shown the role of microbiota in the pathophysiology of these diseases. Much research has been conducted on the role of gut microbiome in the development of rUTI, while little is known yet about vaginal and urinary microbiome and the possible immunological and microscopical mechanisms through which they trigger symptoms. New discoveries and clinical perspectives are arising, and they all agree that a personalized, multi-modal approach, treating vaginal and urinary dysbiosis, may reduce rUTIs more successfully.

Comparison between Robotic Single-Site and Laparoendoscopic Single-Site Hysterectomy: Multicentric Analysis of Surgical Outcomes.

Background and Objectives: Minimally invasive surgery, especially the single-site approach, has demonstrated several advantages in the gynaecological setting. The aim of this study was to compare the surgical outcomes of single-site hysterectomy for benign conditions between the traditional laparoendoscopic approach and robotic surgery. MATERIALS AND METHODS: We consecutively enrolled 278 women between 2012 and 2019 in this multicentre trial. The patients underwent robotic single-site hysterectomy (RSSH) or laparoendoscopic single-site hysterectomy (LESSH) procedures with or without salpingo-oophorectomy for benign indications. Surgical parameters and surgical outcomes were analysed. RESULTS: There was a statistical difference between the two surgical techniques for total operative time (p = 0.001), set-up time (p = 0.013), and anaesthesia time (p = 0.001). Significant differences in intraoperative blood loss were observed (p = 0.001), but no differences were shown for blood transfusion or intraoperative or postoperative complications in the two groups. CONCLUSIONS: LESSH outperformed RSSH in terms of surgical performance and clinical outcomes, with no differences in adverse events.

Laparoscopic Single-Port versus Mini-Laparoscopic Hysterectomy: An International Study.

OBJECTIVES: Laparoendoscopic single-site surgery (LESS) and mini-laparoscopic surgery (Mini-LPS) have been performed with comparable results to conventional laparoscopy. However, there are few data on the comparison between them. Our main objective was to compare LESS and Mini-LPS in terms of surgical time, postoperative pain, and hospital stay in patients who underwent hysterectomy for benign pathology. DESIGN: It is a retrospective international multicentric study carried out in 5 centers including 2 Spanish and 3 Italian. METHODS: Data from patients who underwent hysterectomy for benign pathology between January 1, 2010, and December 31, 2015, were reviewed. We collected the clinical-pathological characteristics of the patients and the perioperative results. The main variables of the study were surgical time, the switch to oral analgesia, and the hospital stay. The two comparison groups in the study included patients undergoing hysterectomy for benign pathology by LESS or by Mini-LPS. The decision to perform the type of procedure was left to the discretion of the surgeon, based primarily on the surgical skills and experience of the center. All data were collected retrospectively by an online encrypted platform. RESULTS: 161 patients were included in the study. 104 (64.6%) patients underwent LESS hysterectomy and 57 (35.4%) Mini-LPS. Median surgical time was significantly longer in the LESS group when compared to the Mini-LPS group (120 vs. 75 min, respectively; p < 0.001). Moreover, longer median hospital stay was observed in the LESS group compared to Mini-LPS (48 vs. 36 h, respectively; p < 0.001). Conversion of the technique to conventional LPS was performed in 4 (2.5%) patients, all of them in the Mini-LPS group (p = 0.015). LIMITATIONS: It is a retrospective study with the biases that this implies. Furthermore, some variables have been incompletely registered in the database, which implies loss of information. This is a nonrandomized study since the decision to intervene with one or another technique was made by the surgeon, which generated 2 nonhomogeneous groups in terms of the number of patients. On the other hand, all the patients who underwent Mini-LPS hysterectomy belonged to the same center, which may have made these results center dependent. CONCLUSIONS: Significant shorter surgical time and shorter hospital stay were observed in patients undergoing Mini-LPS hysterectomy compared to LESS technique; however, intraoperative complications related to instrumentation flaws were higher in the mini-LPS group that required conversion to standard laparoscopy in all cases. Both ultra-minimally invasive techniques seem safe to perform hysterectomies for benign pathology and emphasize the importance in surgical training to adapt them to our current practice.

Comparing the pharmacokinetic and pharmacodynamic qualities of current and future therapies for uterine fibroids.

INTRODUCTION: Uterine fibroids are the most common benign gynecological tumors affecting women of reproductive ages. Although surgery is the definitive treatment choice, several medical approaches have been investigated to control their symptoms. The main issue of currently employed drugs for uterine fibroids is the long-term safety and tolerability profile. Today, new emerging options represent hopeful alternatives that could potentially overcome these limitations. AREAS COVERED: This manuscript aims to give an updated overview of the pharmacodynamic and pharmacokinetic properties of current and new investigational medical drugs for the treatment of symptomatic uterine fibroids. The bibliographic research was conducted by searching alone or combined keywords on the following electronic databases: Medline, PubMed, Embase, Science Citation Index via Web of Science. EXPERT OPINION: The most recent therapeutic strategies for uterine fibroids are represented by gonadotropin-releasing hormone antagonists (GnRH-ants; elagolix and relugolix) and selective progesterone receptor modulators (SPRM; ulipristal acetate). After early promising results, studies on innovative drugs, such as linzagolix (GnRH-ant) and vilaprisan (SPRM) are demanding. In the near future, a deeper knowledge of biological mechanisms at the basis of the genesis and growth of uterine fibroids could pave the way for the development of innovative targeted therapies.

Analysis of surgical outcomes and learning curve of surgical parameters for robotic hysterectomy: a comparison between multiport versus single-site.

Introduction: The primary goal is to analyze the learning curve of surgical parameters (docking, operation and console time) between multiport and single-site robotic hysterectomy techniques, performed by expert laparoscopic surgeons.Material and methods: The trial is a retrospective analysis of 229 patients enrolled between 2010 and 2018 who underwent robotic hysterectomies with bilateral salpingo-oophorectomies (HBSO) for gynecological diseases.Results: Surgical parameters, learning curve and surgical outcomes were analyzed in order to evaluate the transition from multiport to single-site programs, performed by non-expert surgeons using the multiport technique. All surgical times (total, docking and console time) were shorter in the multiport robotic hysterectomy group, while the intraoperative complication rate was lower in the robotic single-site hysterectomy group (p = 0.007). The learning curve of operative, console and docking time significantly decreased more in the robotic-single site hysterectomy group, than in the multiport robotic hysterectomy group over time (p value < 0.001).Conclusions: The direct transition from the laparoscopy program to the single-site approach is feasible and effective in HBSO performed by expert laparoscopic surgeons. The learning curve of robotic single-site hysterectomy shows that the proficiency in this technique requires more cases than the multiport robotic hysterectomy cases and needs more time to fit the surgical step to the single-site platform.

Lymph Node Involvement in Early-Stage Cervical Cancer: Is Lymphangiogenesis a Risk Factor? Results from the MICROCOL Study.

Background: In patients with cervical cancer, the presence of tumoral lymph-vascular space invasion (LVSI) is the main risk factor for pelvic lymph node metastasis (PLNM). The objective of this study was to evaluate the presence of several markers of lymphangiogenesis in early-stage cervical cancer and their correlation with PLNM and tumoral recurrence. Materials and Methods: Seventy-five patients with early-stage cervical carcinoma underwent sentinel lymph node (SLN) sampling in association with complete pelvic lymph node dissection. Primary tumors were stained with the following markers: Ki67, D2-40, CD31 and VEGF-C. A 3-year follow-up was performed to evaluate the disease-free survival. Results: Overall, 14 patients (18.6%) had PLNM. Positive LVSI was seen in 29 patients (38.6%). There was a significant correlation between LVSI evidenced by H/E staining and PLNM (p < 0.001). There was no correlation between high Ki67, CD31, D2-40, and VEGF-C staining with PLNM or tumor recurrence. Conclusions: Our data support that lymphatic spread does not require the proliferation of new lymphatic endothelial cells in early-stage cervical cancer. These results emphasize the importance of pre-existing peritumoral lymphatic vessels in the metastatic process in early cervical cancer. None of the markers of lymphangiogenesis and proliferation assessed in this study were predictive of PLNM or recurrence.

Neoadjuvant Chemotherapy Followed by Radical Surgery versus Concurrent Chemo-Radiotherapy in the Treatment of Locally Advanced Cervical Cancer: A Multicenter Retrospective Analysis.

OBJECTIVES: This study aims to evaluate oncological outcomes in women affected by locally advanced cervical cancer (LACC) treated by neoadjuvant chemotherapy before radical surgery (NACT + RS) or concurrent chemo-radiotherapy (CCRT). METHODS: This was a multicenter retrospective analysis of data related to women with LACC (FIGO stage IB2-IVA), who were treated by NACT + RS or CCRT between November 2006 and January 2018. The first endpoints were the evaluation of disease-free survival (DFS) and overall survival (OS); univariate and multivariate analyses were performed for identifying the prognostic factors independently associated with these oncological outcomes. RESULTS: Overall, 106 women were included in the analysis; 55 of them (51.9%) underwent NACT + RS and 51 (48.1%) CCRT, respectively. Patients in the NACT + RS group had a significant better five-year DFS and five-year OS than those in the CCRT group (77.4% vs. 33.4%, p < .001 and 93.8% vs. 56.5%, p = .003). In the multivariate analyses, treatment choice (NACT + RS or CCRT) was the only independent prognostic factor for predicting both DFS (HR = 3.954; 95 CI = 1.898-8.236; p < 0.001) and OS (HR = 5.330; 95 CI = 1.563-18.178; p = 0.008). CONCLUSIONS: This retrospective study demonstrated an improved survival outcome for patients undergoing NACT + RS compared with those undergoing CCRT. Our findings seem to support the use of NACT before RS as an effective alternative option to CCRT standard therapy.

Characteristics and outcome of BRCA mutated epithelial ovarian cancer patients in Italy: A retrospective multicenter study (MITO 21).

OBJECTIVE: Around 15% of epithelial ovarian cancer (EOC) patients (pts) harbor a germline BRCA1 or 2 mutation, showing different features than BRCA wild-type pts. The clinical and pathological features of an Italian BRCA mutated EOC cohort were described. METHODS: We retrospectively analyzed clinical, pathological and mutational data from a cohort of Italian BRCA mutated EOC pts. treated in 15 MITO centers between 1995 and 2017. RESULTS: Three-hundred thirty-one pts. were recorded. Two-hundred forty (72%) and 91 (27.5%) pts. harbored a BRCA1 and BRCA2 mutation, respectively. Median age at diagnosis was 52 years. The most frequent diagnosis was a high grade serous FIGO III or IV EOC and platinum doublet in first-line was administered to almost all pts. Fifty-three % of them had no residual disease (R = 0) at surgery. Median progression-free-survival (mPFS) after first-line chemotherapy was 29 months. Expected percentage of pts. alive at 5 years was 72.5% (CI 60.2-80.8%) and R = 0 predicted a significantly longer overall survival (OS). Sixty-six pts. (19,9%) had both an EOC and a breast cancer (BC) diagnosis. The first diagnosis was BC in 81,8% of cases with a mean interval between the two diagnoses (IBTDs) of 132.4 months. Mutational data show that the founder mutation c.5266dupC in BRCA1 was the most frequently recorded. CONCLUSIONS: This is the largest Italian BRCA mutEOC cohort. The only predictor of longer OS was R = 0. EOC pts. that developed subsequently a BC are long-term survivors.

Palliative treatment of endometrial cancer: what is the role of anastrozole in elderly women?

BACKGROUND: Type I endometrial cancer is the most common gynaecological tumour in developed countries and its incidence is increasing also because of population aging. The aim of this work is to test the feasibility and safety of anastrozole as palliative treatment of endometrial cancer in elderly women ineligible for standard surgical treatment. METHODS: Patients with histological diagnosis of type I endometrial cancer not suitable for surgical treatment were enrolled in this pilot study. Anastrozole was administered 1 mg daily orally after performing an accurate clinical and radiological staging. Validated questionnaire and self-reported outcomes were used to evaluate quality of life and compliance during the study period. RESULTS: Eight patients with a mean age of 85 (range 80-88 years) were enrolled. All patients had endometrial cancer confined to the uterus, and none progression of disease was observed during the study period. A partial response to the therapy was reported in seven patients, while one patient had stable disease. Tumour symptoms improvement such as pain, vaginal bleeding and vaginal discomfort was reported. The endometrial thickness after twelve months has showed a reduction of 9.25 ± 4.77 mm. The average follow-up time was 18.25 months. Four women died for non oncological reasons, none death related to endometrial cancer was reported. Evaluation of symptoms showed a significant reduction of appetite loss and insomnia, while a significant increase of global health status and fatigue was reported. CONCLUSIONS: Our preliminary data suggested that the palliative use of anastrozole may be a suitable therapy for the proper management of early stages endometrial cancer in elderly women not suitable for surgical treatment with good compliance and tolerance. TRIAL REGISTRATION: 2013000840. Date of registration: 21/09/2013. URL: trials.sanmatteo.loc .

Surgical outcome for robotic-assisted single-site hysterectomy (RSSH) in female-to male reassignment compared to its use in benign gynecological disease: a single center experience.

This study was oriented to assess surgical outcomes, feasibility, and safety of Robotic-assisted Single-Site Hysterectomy and bilateral salpingo-oophorectomy (RSSH/BSO) performed for sexual reassignment compared to indications for the benign gynecologic disease. The present trial is a retrospective analysis of a prospectively collected database. After the exclusion of 3 patients with endometrial cancer on histological specimens, 112 subjects were considered for final analysis: 60 transgender men (TM) and 52 cisgender women (CW). There is a statistical difference in surgical time (total operative time p = 0.0152, docking p = 0.0011, console time p = 0.0001, and anesthesia time p = 0.0061) between TM and CW. Other than in TM, a significant difference in uterine volume (p = 0.0001), Body Mass Index (p = 0.0169), and previous comorbidity (p = 0.0001) was reported. There are no differences in conversion rate, the decrease in hemoglobin and blood loss, hospital stay, intra- and postoperative complications between the two groups. RSSH for sex reassignment appears to be a safe, viable, and cost-effective option with a significant decrease in surgical time compared to other indications for benign disease. In addition, the benefit of this scar-less surgical procedure appears to be more evident in TM's due to the absence of traditional surgical stigmata.

Oncologic Outcomes of Robotic Radical Hysterectomy (RRH) for Patients with Early-Stage Cervical Cancer: Experience at a Referral Cancer Center.

PURPOSE: To evaluate oncologic outcomes of early stage cervical cancer patients who underwent robotic radical hysterectomy (RRH) in a referral center, a retrospective analysis was performed. METHODS: From January 2010 to December 2018, medical records of stage IA2-IIA1 cervical cancer patients, who underwent radical hysterectomy at our institute, were retrospectively reviewed. We focused our analysis on those who underwent RRH. RESULTS: A total of 198 patients were included in the final analysis. Median follow up was 52 months. At last follow-up, 188 (94.9%) women were disease-free, 9 (4.5%) had died, and 1 (0.5%) was alive with recurrent disease. At 4.5 years, PFS was 93.1% (SE ± 2.1) and OS was 95.1% (SE ± 1.8). Stratified by tumor size, PFS for tumor < 2 cm versus tumor ≥ 2 cm was statistically different (96.8% ± 2.3 and 87.9% ± 4.1 respectively, p = 0.01), as well as OS (100% and 89.8% ± 40 respectively, p = 0.01).Stratified by evidence of tumor at time of robotic surgery, PFS was statistically different in women with no residual tumor after conisation versus those with residual disease (100% ± 2.5 and 90.8% ± 2.8 respectively, p = 0.04). A recurrence occurred in 11 patients (5.6%). CONCLUSIONS: Based on our results, we could speculate that robotic approach, along with some technical precautions to avoid spillage, might be safe as primary treatment of early-stage cervical cancer, especially for tumor < 2 cm and in case of no evidence of disease at time of radical hysterectomy after previous conisation.

Comparison between single-site and multiport robot-assisted hysterectomy in obese patients with endometrial cancer: An Italian multi-institutional study.

BACKGROUND: The aim of this study is to compare robotic single-site hysterectomy (RSSH) and robotic multiport hysterectomy (RMPH) for endometrial cancer (EC) in obese patients in terms of surgical outcomes. METHODS: This retrospective study compares RSSH with RMPH in obese patients with EC and FIGO stages I to II divided in three classes according to their body mass index (BMI): class A (30-34.9 kg/m2 ), class B (35-39.9 kg/m2 ), and class C (>40 kg/m2 ). RESULTS: We included 225 patients (RSSH: 76; RMPH: 149). The operative time and estimated blood loss (EBL) were lower in the A class of the RSSH group. The EBL and the conversion rate increased when the BMI increased in the RSSH group. The hospital stay was higher in the A class of the RMPH group. CONCLUSIONS: The advantages of RSSH in terms of reduced invasiveness remain true only in the first BMI class, whereas they are lost when the BMI increased.

Laparoscopic versus robotic hysterectomy in obese and extremely obese patients with endometrial cancer: A multi-institutional analysis.

OBJECTIVE: The aim of this study was to evaluate the surgical and oncological outcome of robotic surgical staging with hysterectomy (RH) plus or less pelvic and aortic lymphadenectomy, compared to the same procedures performed by laparoscopic surgery (LH) in obese patients (BMI≥30 kg/m2) with endometrial cancer. MATERIAL AND METHODS: From October 2001 to April 2017, obese patients (BMI > 30 kg/m2) with primary, histologically confirmed endometrial carcinoma who underwent LH or RH using the Da Vinci Si or Xi Surgical System® (Intuitive Surgical Inc®, 1266 Kifer Road, Building 101 Sunnyvale, CA) were eligible for the study. RESULTS: We identified 655 women with endometrial cancer and BMI >30 kg/m2. Out of 655 patients, 249 (38%) underwent RH and 406 (62%) underwent LH plus or less pelvic and aortic lymphadenectomy. Our study showed that, compared to the 406 patients treated in LPS, 249 patients treated in robotics have a statistically significant difference in terms of increased operating time and a decreased conversion rate. In addition, the rate of pelvic lymphadenectomies in robotic surgeries is twice the one reported in LPS surgeries. Furthermore, a reduction in hospital stay was observed in the robotic group. We observed that the oncological outcomes do not vary according to the surgical approach and BMI variation. CONCLUSIONS: robotic surgery in severely obese women with endometrial cancer is feasible, safe, and reproducible and could be a valid alternative to laparoscopy in the treatment of these patients. Prospective studies could confirm our results.

Survival in clinical stage I endometrial cancer with single vs. multiple positive pelvic nodes: results of a multi-institutional Italian study.

OBJECTIVE: To investigate survival outcomes in endometrioid endometrial cancer (EEC) patients with single vs. multiple positive pelvic lymph nodes. METHODS: We performed a retrospective evaluation of all consecutive patients with histologically proven International Federation of Gynecology and Obstetrics (FIGO) stage IIIC1 EEC who underwent primary surgical treatment between 2004 and 2014 at seven Italian gynecologic oncology referral centers. Patients with pre- or intra-operative evidence of extra-uterine disease (including the presence of bulky nodes) and patients with stage IIIC2 disease were excluded, in order to obtain a homogeneous population. RESULTS: Overall 140 patients met the inclusion criteria. The presence of >1 metastatic pelvic node was significantly associated with an increased risk of recurrence and mortality, compared to only 1 metastatic node, at both univariate (recurrence: hazard ratio [HR]=2.19; 95% confidence interval [CI]=1.2-3.99; p=0.01; mortality: HR=2.8; 95% CI=1.24-6.29; p=0.01) and multivariable analysis (recurrence: HR=1.91; 95% CI=1.02-3.56; p=0.04; mortality: HR=2.62; 95% CI=1.13-6.05; p=0.02) and it was the only independent predictor of prognosis in this subset of patients. Disease-free survival (DFS) and disease-specific survival (DSS) were significantly longer in patients with only 1 metastatic node compared to those with more than 1 metastatic node (p=0.008 and 0.009, respectively). CONCLUSION: The presence of multiple metastatic nodes in stage IIIC1 EEC represents an independent predictor of worse survival, compared to only one positive node. Our data suggest that EEC patients may be categorized according to the number of positive nodes.