Giulia Pellecchia

The Relationship Between the Vaginal Microbiota and the Ovarian Cancer Microenvironment: A Journey from Ideas to Insights

Background: The tumor microenvironment offers a new perspective in gynecologic oncology. In ovarian cancer, numerous preclinical studies, especially organoid models, have highlighted cellular, immune, and biochemical mechanisms. Beyond these sophisticated findings, more practical aspects require attention, such as the role of vaginal microbiota, which represents an interplay between external agents and internal genitalia, and its potential profiling role in early detection beyond the promise of microbiota-targeted therapies. Objectives: This review aims to assess whether such a correlation is speculative or scientifically grounded. Methods: A focused literature search was conducted on vaginal microbiota and its correlation with ovarian cancer to define the current state of knowledge. Results: Mixed outcomes have been reported, yet there is a rational and scientific basis supporting further investigation. Clinical approaches increasingly consider vaginal microbiota as relevant. However, we have to say that most available evidence is still preliminary and largely preclinical to set realistic expectations for readers. Although additional studies are needed, emerging insights highlight its importance and practical implications. We present a diagnostic–therapeutic management flowchart summarizing current evidence). Discussion: Most links between the vaginal microbiota and ovarian cancer are correlational rather than causal. The idea that microbes ascend from the vagina to the ovaries is proposed but still definitely not demonstrated. Confounding factors like age, hormones, and BRCA status complicate interpretation, and ovarian cancer itself could secondarily alter the microbiota. Mechanistic studies and longitudinal data are still needed to clarify whether dysbiosis contributes to carcinogenesis or is merely a consequence. As gynecologists, we summarize key aspects and emphasize to colleagues the importance of incorporating these findings into daily clinical practice. Vaginal dysbiosis should be considered not only a local imbalance but also a potential strategy for primary cancer prevention. Conclusions: Future research on the tumor microenvironment and vaginal microbiota will expand scientific knowledge and guide innovative preventive and therapeutic strategies.

Survival and perioperative outcomes of pelvic exenteration in primary advanced and recurrent endometrial carcinoma: A systematic review and meta-analysis

To assess survival and perioperative complications and mortality of pelvic exenteration (PE) in recurrent and advanced endometrial carcinoma (EC) patients. A systematic review and a meta-analysis was performed searching 7 electronic databases from their inception to May 2024 for all peer-reviewed studies that reported as a study outcome at least the 5 years-overall survival (OS) of PE in recurrent and/or advanced EC patients. Our outcomes were 5 year-OS from PE as primary outcome, and all extractable outcomes about PE survival [overall OS, 5 year- and overall disease specific survival (DSS), 5 year- and overall progression free survival (PFS)] and perioperative mortality and complications. Rates of survival outcomes and perioperative mortality and complications were calculated as individual and pooled estimates, with 95 % confidence intervals (CI). Subgroup analyses were planned for all study outcomes based on recurrent or advanced EC, separately. 6 studies with 166 patients were included. In women underwent PE for advanced or recurrent EC, pooled rate was: 41.7 % (95 % CI: 25.6-57.8 %) for 5 year-OS; 30.4 % (95 % CI: 14.9-45.8 %) for 5 year-DSS; 26.6 % (95 % CI: 10.6-42.5 %) for overall DSS; 51.8 % (95 % CI: 25.6-78.0 %) for 5 year-PFS; 9.7 % (95 % CI: 5.7-16.1 %) for perioperative mortality; 56.1 % (95 % CI: 32.3-76.4 %) for perioperative complications. Subgroup analyses were suitable exclusively in the "recurrent EC" subgroup and showed even worsened outcomes. In women with advanced or recurrent EC, PE shows not encouraging survival outcomes, with relatively high rates of perioperative mortality and complications. These outcomes further worsened in the subgroup of only recurrent EC. However, they should be confirmed by more updated studies.

Is there a role for the sentinel lymph node in endometrial atypical hyperplasia? Insights from an ESGO-accredited Institution

This study investigates the outcomes of patients with premalignant endometrial findings on biopsy who underwent hysterectomy with sentinel lymph node (SLN) excision and were subsequently diagnosed with endometrial cancer (EC). It aims to highlight the role of nodal assessment in guiding postoperative treatment strategies. Additionally, the study compares surgery complication rates between patients who underwent SLN mapping and those who did not. This retrospective, observational, single-center study was conducted at Udine Hospital between April 2021 and July 2024. 63 patients diagnosed with atypical hyperplasia on endometrial biopsy who underwent hysterectomy and bilateral salpingo-oophorectomy, with or without SLN mapping, were included. All procedures were performed using minimally invasive surgery. Of the 63 patients, 35 (55.6 %) had confirmed atypical hyperplasia on uterine pathology, while 23 (36.5 %) were diagnosed with EC on final pathology. Of the patients who underwent SLN mapping, 18 (43 %) received a final diagnosis of EC and were accurately staged and treated accordingly. In contrast, within the group of patients treated without SLN mapping, 5 (24 %) were diagnosed with EC on final pathology and didn't receive proper staging. No nodal metastases were found in both groups. There was no statistically significant difference in operating time and complication rates between the two groups (with or without SLN mapping), further supporting the procedure's safety. This study's findings underscore the significance of incorporating SLN mapping into hysterectomy and bilateral salpingo-oophorectomy for patients with atypical hyperplasia. This approach enhances accurate staging for patients diagnosed with endometrial cancer on final pathology.

Impact of optimal secondary cytoreductive surgery on survival outcomes in women with recurrent endometrial carcinoma: A systematic review and meta‐analysis

AbstractBackgroundManagement of recurrent endometrial carcinoma (EC) represents a challenge. Although a complete resection of visible disease at secondary surgery (R0) is recommended, the impact of R0 on survival outcomes is unclear and pooled data are lacking.ObjectiveTo quantitatively assess the impact of R0 on survival outcomes in women with EC recurrence.Search StrategyA systematic review and meta‐analysis was performed searching eight electronic databases from their inception up to January 2024.Selection CriteriaAll peer‐reviewed studies that assessed quantitatively the impact of R0 on survival outcomes in women at first EC recurrence were included.Data Collection and AnalysisHazard ratio (HR) with 95% confidence interval (CI) for death of any cause and secondary recurrent or progressive disease in women with EC recurrence who underwent R0 compared to non‐optimal secondary surgical cytoreduction (R1) were pooled and assessed at both univariable and multivariable analyses.Main ResultsThree studies with 442 patients were included. At univariate analysis, in women with EC recurrence and R0 compared to women with EC recurrence and R1, pooled HR was 0.451 (95% CI: 0.319–0.638) for death from any cause, and 0.517 (95% CI: 0.298–0.895; p = 0.019) for recurrent or progressive disease.At multivariate analysis, in women with EC recurrence and R0 compared to women with EC recurrence and R1, pooled HR was 0.447 (95% CI: 0.255–0.783; p = 0.005) for death from any cause, and 0.585 (95% CI: 0.359–0.952; p = 0.031) for recurrent or progressive disease.ConclusionIn women with EC recurrence, R0 is an independent prognostic factor, decreasing the risk of death from any cause by approximatively 55%, and of recurrent or progressive disease by approximatively 40%, compared to R1.

Reproductive, obstetrical and oncological outcomes of fertility-sparing treatment for cervical cancer according to the FIGO 2018 staging system: A systematic review

We assessed reproductive, obstetrical, and oncological outcomes in patients who underwent fertility-sparing treatment by including studies that adhere to the FIGO 2018 staging system. Data on recurrence, mortality, pregnancy rate, live birth rate, and preterm delivery rate were collected. In patients with stages IA1, IA2, and IB1, the recurrence rate was 4.7 % and the death rate was 0.6 %. For patients with stage IB2, the recurrence rate was 12.1 % and the death rate was 3.2 %. Pregnancy rates for conization/simple trachelectomy and radical trachelectomy were 61.7 % and 50 %, respectively. A higher live birth rate (84.4 % vs 58.6 %), and lower preterm birth rate (18.3 % vs 33.3 %) were observed in patients undergoing conization compared to radical trachelectomy. We found a recurrence rate of 4.7 % in patients with stage less than or equal to IB1 and 12.1 % in those with stage IB2. A higher rate of preterm delivery was observed in patients who underwent radical trachelectomy.

Exploring the cost-effectiveness of the OSNA method for patients facing endometrial cancer: Insights from a single-institution experience

The one-step nucleic acid amplification (OSNA) method has emerged as a potential alternative to ultrastaging for diagnosing lymph node metastasis. This study aims to assess the cost-effectiveness of the OSNA technique compared to ultrastaging for detecting SLN metastasis in patients with early-stage endometrial cancer (EC). This retrospective, observational, single-center study included 30 patients with EC who underwent surgical treatment. SLN mapping was performed using an intracervical injection of indocyanine green. SLNs were analyzed and classified as negative, as having isolated tumor cells, micrometastases, or macrometastases. The study evaluated and quantified the costs of the OSNA and ultrastaging procedures in euros. A total of 54 lymph nodes were analyzed using both the OSNA and ultrastaging methods. Concordant negativity was identified in 48 cases (89 %), while micrometastases were detected concordantly in 1 case (1.8 %). The cost for a single ultrastaging lymph node analysis, including immunohistochemistry, is approximately € 250, with a total processing time of 2 days. The cost for a single OSNA analysis is approximately € 236, boasting a significantly shorter processing time of 30-40 min. While materials and staff costs are comparable between both techniques, considering time-related expenses, the OSNA method proves to be more cost-effective than ultrastaging (p < 0.001). The OSNA method demonstrates diagnostic accuracy comparable to histopathological examination in detecting lymph node metastases, reinforcing its reliability for lymph node assessment in patients with EC. Our cost analysis reveals that the OSNA method is more cost-effective than ultrastaging when time-related expenses are considered.