Stefano Uccella

Sentinel lymph node biopsy in apparently early-stage epithelial ovarian cancer: a systematic review and meta-analysis

To evaluate the detection rate, sensitivity, and negative predictive value (NPV) of sentinel lymph node (SLN) biopsy in patients with apparently early-stage epithelial ovarian cancer (EOC). A systematic search of multiple electronic databases was conducted from inception to October 31, 2025. Studies reporting detection rate, sensitivity, and NPV of SLN biopsy in apparently early-stage EOC, with completion pelvic and para-aortic lymphadenectomy as reference standard, were included. Study selection, risk-of-bias assessment, and data extraction were independently performed by four reviewers. Pooled estimates with 95 % confidence intervals (CI) were calculated using random-effects models on a per-patient basis and by anatomical site. Heterogeneity was assessed using the I Fourteen studies comprising 365 patients were included. Most studies used indocyanine green injected into the infundibulopelvic ligament for para-aortic mapping and the utero-ovarian ligament for pelvic mapping. The pooled para-aortic detection rate was 79.9 % (95 %CI 66.1-91.4 %; I In apparently early-stage EOC, SLN biopsy shows acceptable para-aortic detection but limited pelvic detection. Nonetheless, sensitivity and NPV indicate high diagnostic accuracy. Further studies are needed to optimize pelvic mapping strategies and confirm these findings. At present, sentinel lymph node mapping in apparently early-stage epithelial ovarian cancer should be regarded as investigational and not as standard of care.

Reply to Research on intrauterine manipulators for endometrial cancer: attention to study-level characteristics

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

To evaluate the sensitivity and specificity of sentinel-lymph-node mapping compared with the gold standard of systematic lymphadenectomy in detecting lymph node metastasis in apparent early stage ovarian cancer. Multicenter, prospective, phase II trial, conducted in seven centers from March 2018 to July 2022. Patients with presumed stage I-II epithelial ovarian cancer planned for surgical staging were eligible. Patients received injection of indocyanine green in the infundibulo-pelvic and, when feasible, utero-ovarian ligaments and sentinel lymph node biopsy followed by pelvic and para-aortic lymphadenectomy was performed. Histopathological examination of all nodes was performed including ultra-staging protocol for the sentinel lymph node. 174 patients were enrolled and 169 (97.1 %) received study interventions. 99 (58.6 %) patients had successful mapping of at least one sentinel lymph node and 15 (15.1 %) of them had positive nodes. Of these, 11 of 15 (73.3 %) had a correct identification of the disease in the sentinel lymph node; 7 of 11 (63.6 %) required ultra-staging protocol to detect nodal metastasis. Four (26.7 %) patients with node-positive disease had a negative sentinel-lymph-node (sensitivity 73.3 % and specificity 100.0 %). In a multicenter setting, identifying sentinel-lymph nodes in apparent early stage epithelial ovarian cancer did not reach the expected sensitivity: 1 of 4 patients might have metastatic lymphatic disease unrecognized by sentinel-lymph-node biopsy. Nevertheless, 35.0 % of node positive patients was identified only thanks to ultra-staging protocol on sentinel-lymph-nodes.

The Female Reproductive Tract Microbiota and Endometrial Cancer: A Systematic Review

This systematic review aimed to summarize the available evidence on the associations between the female reproductive tract microbiota and endometrial cancer (EC). While gut microbiota has been studied extensively, microbial communities within the endometrium, cervix, and vagina remain relatively understudied. A systematic literature search was conducted in PubMed, Scopus, Web of Science, EMBASE, and the Cochrane Library for studies published up to January 2025. Predefined PECO-based criteria included studies on women or human cell models assessing genital tract microbiota in EC versus non-EC controls, focusing on composition, diversity, or function; reviews and non-microbiota studies were excluded. A total of 21 studies were included. Overall, there was a consistent depletion of protective Lactobacillus species and enrichment of anaerobic, pro-inflammatory bacteria like Prevotella, Atopobium, and Porphyromonas in EC tissues. Beta-diversity was significantly different between EC and controls across studies, indicating distinct microbial profiles. Some studies also identified fungal and viral taxa associated with EC, and functional assays demonstrated that certain species could modulate host immune responses or promote tumor growth. Despite methodological heterogeneity and the lack of evidence supporting causality due to the observational design, the findings support an association between altered genital tract microbiota and EC.

Intrauterine manipulator during hysterectomy for endometrial cancer: a systematic review and meta-analysis of oncologic outcomes

This study aimed to assess the effects on oncologic outcomes of intrauterine manipulator use during laparoscopic hysterectomy for endometrial cancer. A systematic literature search was performed by an expert librarian in multiple electronic databases from inception to January 31, 2023. We included all studies in the English language that compared oncologic outcomes (recurrence-free, cause-specific, or overall survival) between endometrial cancer patients who underwent total laparoscopic or robotic hysterectomy for endometrial cancer with vs without the use of an intrauterine manipulator. Studies comparing only peritoneal cytology status or lymphovascular space invasion were summarized for completeness. No selection criteria were applied to the study design. Four reviewers independently reviewed studies for inclusion, assessed their risk of bias, and extracted data. Pooled hazard ratios with 95% confidence intervals were estimated for oncologic outcomes using the random effect model. Heterogeneity was quantified using the I Out of 350 identified references, we included 2 randomized controlled trials and 12 observational studies for a total of 14 studies and 5,019 patients. The use of an intrauterine manipulator during hysterectomy for endometrial cancer was associated with a pooled hazard ratio for recurrence of 1.52 (95% confidence interval, 0.99-2.33; P=.05; I Intrauterine manipulator use during hysterectomy for endometrial cancer was neither significantly associated with recurrence-free and overall survival nor with positive peritoneal cytology or lymphovascular space invasion, but further prospective studies are needed.

Exploring isolated tumor cells entity in endometrial cancer

Endometrial cancer (EC) management includes nodal staging and molecular classification. Despite molecular advancements, the biological significance of isolated tumor cells (ITC) in EC remains unclear. This study aimed to characterize ITC in the context of pathological and molecular features MATERIALS AND METHODS: A multicenter, retrospective analysis included EC patients diagnosed between June 2018 and May 2024 who underwent surgical staging via sentinel lymph node (SLN) biopsy and molecular profiling. ITC cases detected through SLN ultrastaging or One Step Nucleic Acid Amplification (OSNA) were compared with N0 and N + (micro-/macrometastasis) groups. Among the 1821 patients included, nodal status was N0 in 84.5 %, ITC in 5.1 %, micrometastases in 5.3 %, and macrometastases in 4.5 %. ITC patients exhibited deep myometrial invasion in 67.7 % of cases vs. 28.7 % in N0 (p < 0.001). Diffuse lymphovascular space invasion (LVSI) was significantly higher in ITC (52.1 %) than N0 (12.2 %, p < 0.001). MMR deficiency was more frequent in ITC (33.3 %) vs. N0 (25.0 %, p = 0.07). POLE mutations were more common in N0 (4.2 %) and ITC (3.1 %) vs. N + (1.1 %), though not statistically significant. p53-abnormal tumors were significantly associated with N + status (19.4 %) compared to ITC (7.3 %, OR 0.33, p = 0.008). No relapses occurred among ITC patients with low-risk features. These findings suggest that ITC may represent an early form of nodal involvement, biologically distinct from micro- and macrometastases. The association with MMR deficiency and the absence of aggressive markers such as p53 abnormalities support a less aggressive profile. Integrating molecular and pathological features may refine risk stratification and inform management strategies for EC patients with ITC.

Performance of molecular classification in predicting oncologic outcomes of fertility-sparing treatment for atypical endometrial hyperplasia and endometrial cancer

Endometrial cancers can be classified into 4 molecular sub-groups: (1) POLE mutated (POLEmut), (2) mismatch repair deficiency/microsatellite-instable (MMRd/MSI-H), (3) TP53-mutant or p53 abnormal (p53abn), and (4) no specific mutational profile (NSMP). Although molecular classification is increasingly applied in oncology, its role in guiding fertility-sparing treatments for endometrial cancer remains unclear. This study examines the prognostic role of molecular classification in fertility-sparing treatment and its potential to guide treatment decisions. We conducted a systematic review and meta-analysis of studies applying molecular classifiers in patients with endometrial cancer or atypical hyperplasia who underwent fertility-sparing treatment (International Prospective Register of Systematic Reviews, identification CRD42024555559). A literature search was performed across Scopus, PubMed/MEDLINE, ScienceDirect, and the Cochrane Library (2013-February 2024). Studies included full-text English articles with pre-operative assessments (histology, magnetic resonance imaging, or ultrasound) and molecular classification through next-generation sequencing or Proactive Molecular Risk Classifier for Endometrial Cancer. Both randomized controlled trials and observational studies were considered. Outcomes included complete response, partial response, stable disease, progression, and recurrence, with pooled analyses performed. Eight retrospective cohort studies comprising 363 patients met the inclusion criteria. Next-generation sequencing was used in 5 studies. The distribution of molecular sub-groups was POLEmut (5.8%), p53abn (3.3%), MMRd/MSI-H (12.1%), and NSMP (78.8%). Complete response and recurrence rates were POLEmut (66.6% and 14.3%), p53abn (50% and 33%), MMRd/MSI-H (48.8% and 42.8%), and NSMP (78.4% and 18.4%). Significant differences in complete response (p <.001) and recurrence rates (p = .005) were found across sub-groups. Pairwise analysis revealed lower complete response and higher recurrence rates for MMRd/MSI-H (p <.001, p = .01) and lower response for p53abn (p = .03) than for NSMP. POLEmut did not show superior success to other groups. Molecular classification indicates prognostic value in fertility-sparing treatment for endometrial cancer. NSMP had the highest response rates, whereas MMRd/MSI-H and p53abn were associated with poorer outcomes.

Fertility-Sparing Strategies for Early-Stage Endometrial Cancer: Stepping towards Precision Medicine Based on the Molecular Fingerprint

Endometrial cancer represents the fifth most common cancer in women, and the most common gynecological malignancy in developed countries [...]

Uterine manipulator in endometrial cancer: we are still far from the answer

Hydatidiform Mole with Coexisting Normal Pregnancy: A Systematic Review and Individual Participant Data Meta-Analysis

Background and Objectives: This study aimed to evaluate obstetric, neonatal, and oncologic outcomes of pregnancies complicated by a hydatidiform mole coexisting with a live fetus (HMCF) carried beyond viability, and to assess the impact of delivery mode on outcomes. Materials and Methods: A systematic review and individual participant data meta-analysis included HMCF cases progressing beyond 23 weeks. Obstetric and neonatal outcomes, delivery patterns, and oncologic risks were analyzed. Results: Among 118 pregnancies complicated by HMFC (124 newborns), most were complete moles (87%). Median delivery occurred at 31.6 weeks, with over half before 32 weeks. Common complications included vaginal bleeding (59%), preeclampsia (30%), and hyperthyroidism (18%). Cesarean delivery was performed in 79% of cases, often for mole-related factors, but was not associated with reduced maternal or oncologic risk. Neonatal deaths occurred exclusively in infants delivered ≤32 weeks, highlighting extreme prematurity as the key determinant of survival. Severe preeclampsia was strongly linked to earlier delivery. Conclusions: With close monitoring, continuation of HMCF pregnancies is possible. Neonatal mortality is mainly driven by prematurity, which appears to be an indirect consequence of HMFC through the development of mola-associated complications. Cesarean section does not appear to improve maternal and oncologic outcomes. Vaginal delivery can be considered when no standard contraindications exist.

Surgical treatment of large adnexal masses: a retrospective analysis of 330 consecutive cases

Patent Blue SLN in Early Ovarian Cancer Prospective Study (FIGO I-II) Evaluating Patent Blue SLN Mapping. Injection Into IP/UO Ligaments in Situ. Goals: Assess Feasibility and Accuracy vs Standard Lymphadenectomy to Minimize Surgical Morbidity

the standard of care in case of early ovarian cancer (stage I or II) is a complete surgery. This surgery includes : hysterectomy (remove of the uterus), bilateral salpingo-oophorectomy (remove of the adnexa), omentectomy (remove of the epiploon), bilateral pelvic lymphadenectomy (remove of pelvic lymph nodes) and para-aortic lymphadenectomy (remove of para-aortic lymph nodes). This procedure is diagnostic, curative and prognostic surgery. In fact, it allows us provider care giver to stratify the stage of the cancer, hence we give the appropriate adjuvant therapy. However, this surgery, especially the extended lymphadenectomy, is associated with some risks: lymphocele, vessel injury, blood loss, morbidity, long recovery period ... In order to reduce these risks, we propose a sentinel lymph node biopsy. This intervention allows us to detect first lymph node relay whether pelvic or para-aortic. In our study, we chose the patent blue dye as a tracer. This tracer is widely used in oncologic surgery (for example in breast cancer) and approved but not in ovarian cancer yet. During surgery for early stage ovarian cancer, we will inject the patent blue dye on both side of the ovarian tumor. Then, we will check for first colorful lymph node, in both pelvic and para-aortic regions. We will send these dissected lymph node to pathology for analysis. Finally, we will continue the procedure as the standard of care. Our objective is to compare the results between the sentinel lymph node and the complete lymphadenectomy and to study the technique of sentinel lymph node biopsy using the blue patent dye as tracer.

Uterine Manipulator Versus No Uterine Manipulator in Endometrial Cancer Trial

Minimally invasive surgery is the recommended approach in endometrial cancer (EC) patients based on the results of two randomized controlled trials, given its advantages without compromised oncologic outcomes. The uterine manipulator is commonly used in benign and malignant pathologies to perform a laparoscopic or robotic hysterectomy. However, although regularly used, the uterine manipulator adoption in EC is a controversial technical aspect due to the raised concerns regarding the possible risk of disruption of the tumor mass, the spread of malignant cells, and seeding of the disease, particularly at the level of the vaginal cuff or spread of tumor cells, with increased risk of recurrence and death due to EC. On that basis, given that hysterectomy without a uterine manipulator is feasible, only a randomized controlled trial comparing oncologic outcomes in EC patients after use versus not use of the uterine manipulator will be able to provide high-quality evidence to answer this critical question and allow or exclude the use of a uterine manipulator during minimally invasive hysterectomy for EC.