Investigator
University Of Pisa
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.
Surgical timing in advanced ovarian cancer during the TRUST trial era: A systematic review, meta-analysis and study-level meta-regression of randomized controlled trials
The best surgical timing for advanced epithelial ovarian cancer, whether primary debulking surgery or interval debulking surgery, remains debated. Recent data, including the preliminary ones from TRUST trial, necessitates an updated critical evaluation. A systematic search of PubMed identified only randomized controlled trials comparing interval debulking surgery versus primary debulking surgery in patients with newly diagnosed advanced ovarian cancer. Primary outcomes included overall survival (OS) and progression-free survival (PFS). A random-effects meta-analysis, meta-regression, cumulative synthesis, and leave-one-out influence analysis were performed. A total of 2303 patients were included. Compared to primary debulking surgery, interval debulking surgery was associated with lower rates of postoperative complications (OR = 0.37; 95 % CI: 0.18-0.79; P = 0.01) and mortality (OR = 0.23; 95 % CI: 0.09-0.57; P = 0.002). Meta-analysis showed higher rates of complete cytoreduction with interval debulking surgery (OR = 3.84; 95 % CI: 2.14-6.91; P < 0.00001) and lower rates of macroscopic residual disease (OR = 0.20; 95 % CI: 0.13-0.30; P < 0.00001). Pooled data revealed no significant difference in OS (HR = 0.95; 95 % CI: 0.87-1.04; P = 0.26) or PFS (HR = 0.94; 95 % CI: 0.85-1.03; P = 0.16). Subgroup analyses by stage and residual disease confirmed similar survival outcomes. The meta-regression results suggested that even in trials with very high complete cytoreduction rates, no clinically meaningful OS benefit was observed for upfront surgery. In conclusion, interval debulking surgery offers comparable survival outcomes to primary debulking, with reduced perioperative morbidity and mortality, supporting its role as a valid surgical alternative. PROSPERO REGISTRATION NUMBER: CRD420251105308.
Correspondence on ‘Sentinel lymph node assessment in patients with atypical endometrial hyperplasia: a systematic review and meta-analysis’ by Vieira-Serna et al
Pressurized intraperitoneal aerosol chemotherapy (PIPAC) with cisplatin and doxorubicin in patients with ovarian cancer: A systematic review
PIPAC consists in delivering normothermic chemotherapy solution directly into the peritoneal cavity as an aerosol under pressure. Currently PIPAC is considered as a palliative treatment for patients suffering from non-resectable peritoneal carcinomatosis. We performed a SR to assess tolerance and response of this novel method among patient with OC. We searched electronic database PubMed, Embase, Web of Science, Clinical Trials.gov. We only included clinical studies reporting PIPAC with cisplatin and doxorubicin in patients with ovarian cancer. This systematic review included 4 studies. In 3 studies all patients were pretreated with cytoreductive surgery, in 1 study surgery was performed in 8/34 (23 %) patients. Mean PCI at first PIPAC procedure ranged from 16.3 to 19.6. All studies reported the proportion of patients with ascites at the first PIPAC with a pooled rate of 48,3 %. Pooled rate of CTCAE Grade 3 toxicity calculated on the total number of PIPAC was 6 % and Grade 4 was 0.9 %. One study reported two cases of small bowel perforation related or potentially related to PIPAC. On study reported a cumulative survival after 400 days of 62 % and a mean actuarial survival time of all patients who underwent PIPAC of 442 days. In another study the mean time to progression was 144 days (95 % CI 122-168 days). This systematic review demonstrated that PIPAC with cisplatin and doxorubicin appear to have a good safety profile with low toxicity and encouraging trend in terms of overall survival.
Robotic single-port (da Vinci SP) versus multiport (da Vinci Xi) for the treatment of atypical endometrial hyperplasia and endometrial cancer: A multi-institutional comparison of surgical outcomes
The da Vinci SP robotic platform offers a novel single-port approach for minimally invasive surgery. Despite its potential, data on its safety and performance in gynecologic oncology remain limited. We aimed to compare surgical outcomes of da Vinci SP versus da Vinci Xi systems in the staging of endometrial cancer (EC). This is a multi-institutional study. Data of consecutive patients with apparent early-stage EC or atypical endometrial hyperplasia who underwent robotic surgery between January 2023-March 2025 were collected. The primary outcome was to compare the surgical outcomes between da Vinci SP and da Vinci Xi. A total of 189 patients were included: 97 (51.3 %) underwent SP surgery and 92 (48.7 %) Xi. The median (range) of operative time, estimated blood loss, and postoperative hospital stay were comparable for SP and Xi groups (140 [70-296] vs. 143 [60-297] min, p = 0.66, 40 [0-250] vs. 64 [0-1300] mL, p = 0.12, 3 [1-11] vs. 3[1-10] days, p = 1). Docking time was significantly shorter in the SP group (10 [4-31] vs. 12 [7-30] min for SP and Xi, respectively, p = 0.004). Intraoperative or post-operative complications rates were comparable (p = 0.30 and p = 0.14,respectively). The patient-reported pain score was significantly lower at 12h and 24h in the Xi group (p = 0.001), while was comparable at 48h after surgery (p = 1). The da Vinci SP system appears to be non-inferior to the multiport da Vinci Xi for surgical staging of early-stage EC. Comparable perioperative outcomes support its clinical use, although patient selection criteria and long-term results require further investigation.
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.
Mesonephric-Like Adenocarcinomas a Rare Tumor: The Importance of Diagnosis
Mesonephric-like adenocarcinomas (MLA) are rare neoplasms that arise in the uterine body and ovary and have been added to the World Health Organisation’s recent 2020 classification of female genital cancers. The pathogenesis of MLA is unknown and it remains debated whether they represent mesonephric carcinomas (Wolffian) arising in the endometrium/ovary or endometrioid carcinomas (Müllerian) closely mimicking mesonephric carcinomas. Here we report the case of a 57-year-old woman with an initial misdiagnosis of endometrioid adenocarcinoma on diagnostic biopsy. The patient came to our clinical evaluation for the appearance of menometrorrhagia complicated by anemia for several months. Therefore, she underwent pelvic echo-flowmetry, with indication for diagnostic hysteroscopy with endometrial biopsy, which yielded a positive result for endometrioid endometrial adenocarcinoma. Following staging CT scan and targeted examinations on pulmonary findings, the patient underwent surgery with surprise of definitive diagnosis deponent for endometrial MLA. Our intention is to establish a brief review of the scientific evidence in the literature and the tools available for a correct histological diagnosis, in the light of the scant anatomopathological evidence. Our question gives rise to the motive for the publication: is immunohistochemistry the right way to resolve the diagnostic error at histology, which is usually the only source of diagnostic certainty? This case is intended to alert of diagnostic error that risked having the patient treated as a neoplasm with a favorable prognosis and low degree of aggressiveness instead of for a very aggressive and poor prognosis tumor such as MLA.
Risk reducing surgery with peritoneal staging in BRCA1-2 mutation carriers. A prospective study
International guidelines recommend risk-reducing salpingo-oophorectomy (RRSO) in BRCA1-2 mutations carriers to decrease ovarian cancer occurrence. In this prospective study, we describe the incidence of occult malignancies and the surgical outcomes in asymptomatic BRCA mutation carriers submitted to RRSO. Data on BRCA1-2 carriers undergoing RRSO with peritoneal washing and peritoneal/omental biopsies (PeS), between January 2019 until March 2021, were prospectively collected. A total of 132 patients were enrolled: 74 BRCA1 and 58 BRCA2 mutation carriers. 31.1% women underwent RRSO and PeS (16.2% of BRCA1 and 50% of BRCA2 carriers), while 68.9% patients were submitted also to concomitant hysterectomy. Almost all the procedures (99.2%) were performed by minimally invasive surgery. Postoperative complications occurred in twelve patients (9.1%): 10 in the concomitant hysterectomy group and two complications in the RRSO group. At the final pathological examination, 6 (4.5%) occult carcinomas were diagnosed: 3 fallopian tube carcinomas, one ovarian carcinoma and two serous tubal intraepithelial carcinomas (STICs), with negative PeS. Median age of occult carcinomas patients at RRSO was 54 (range: 48-79) years. The mean follow up was 20 (range: 7-34) months. During the follow up, no primary peritoneal cancer has been diagnosed. Occult pathologic findings in RRSO occurred in 4.5% (3% invasive carcinomas, STIC 1.5%) among our patients. The routine use of peritoneal biopsies does not improve the detection of occult malignancies. Our data confirm the importance of timely performing RRSO in BRCA1-2 carriers.
Clinical impact of surgical energy device (Caiman®) IN elderly patients with Endometrial Cancer (protocol ID: Cineca)
To investigate the clinical performance of the Caiman® energy device in class A radical laparoscopic hysterectomy (RLH) according to Querleu-Morrow classification, combined with bilateral salpingo-oophorectomy (BSO) and pelvic lymph node assessment in elderly patients with early-stage endometrial cancer (EC), specifically focusing on hemostatic effectiveness and safety. Single-institution, prospective observational study. Gynecologic Oncology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. Forty-three women over 65 years with FIGO stage IA or IB endometrioid EC were enrolled from September 2021 to August 2023. Use of Caiman® energy device in RLH combined with BSO and pelvic lymph node assessment in elderly patients. The primary endpoint was operative time, with secondary endpoints including perioperative outcomes and postoperative complications. Results demonstrated a median surgical time of 135 min, with no significant intraoperative complications attributed to the Caiman® device. Postoperative complications were minimal, with no severe complications (Grade 4 or 5) and a median hospital stay of two days. The study highlights the advantages of the Caiman® in enhancing surgical efficiency while minimizing risks for elderly patients, suggesting its potential for improving resource allocation and patient outcomes in oncologic surgery. The findings of this study suggest the feasibility of using the Caiman® device for surgical procedures in elderly patients with early-stage endometrial cancer. Future prospective randomized trials are needed to establish its efficacy compared to traditional surgical methods.
The exciting journey of progress: Exploring FIGO 2023 staging for endometrial cancer at a leading ESGO institution
The 2023 FIGO staging of endometrial cancer integrates tumor grade and histology along with molecular features that recognize the prognostic significance of p53 and POLE mutations, accounting for potential conflicts such as lymphovascular space invasion and subserosal invasion. In this single-institution retrospective study, data were collected on 229 endometrial cancer patients from January 2020 to September 2024 and re-stage them according to FIGO 2023 criteria. From FIGO stage 2009 IA, 70 patients do not cross stage (21 are FIGO 2023 IA1 and 49 IA2), 8 patients are upgraded to FIGO IC because of aggressive histotype; 1 is upstaged because of substantial LVSI, and 12 because of aggressive myoinfiltrating tumors (23 % of upstaging). From FIGO 2009 stage IB 34 patients remain in FIGO 2023 IB, while 5 become stage IIB (LVSI) and 27 IIC (aggressive myoinfiltrating), for a total of 32 upstages (48 % of upstaging). Within FIGO 2009 stage II, no proper upstage was possible. We observed a statistical correlation between stages and BMI, as well as between stages and age, for both FIGO 2009 (p = 0.009 and p < 0.001 respectively) and FIGO 2023 (p = 0.002 and p = 0.003 respectively) classifications. Additionally, a correlation was found between tumor grade and BMI (p = 0.02). The FIGO 2023 staging system is gaining importance as recent studies highlight the role of molecular classification in prognosis and personalized therapy. Updating our study's follow-up data will clarify its impact in clinical practice.
Study of the Role of the Tumor Microenvironment in Ovarian Cancer ( MICO ): A Prospective Monocentric Trial
ABSTRACT Background Ovarian cancer (OC) is one of the most aggressive tumors requiring new therapeutic approaches. Immunotherapy represents an opportunity, but to date, OC patients do not appear to benefit from current protocols. A better understanding of the composition of the tumor microenvironment (TME), especially in its immune components, could unveil mechanisms of immune suppression in a useful way to predict response to therapies and develop new therapeutic approaches. Method The MICO (tumor MICroenvironment of Ovarian cancer) study is a single‐center observational study. Starting from peritoneal biopsy of high‐grade serous ovarian carcinoma (HGSOC), the purpose of the MICO study is to generate tumor patient‐derived organoid (PDOs) cultures and evaluate the concordance between in vitro platinum‐based chemotherapy sensitivity and in vivo sensitivity. Simultaneously, we will characterize through multiparameter cytofluorimetric analysis the composition of the OC TME, focusing on B lymphocytes and mast cells whose roles in ovarian cancer remain controversial and underinvestigated. Furthermore, patients experiencing recurrence will be longitudinally followed to monitor changes in the TME composition and the responsiveness of PDOs to in vitro stimulation with drugs. Discussion The association between the composition of the TME, the reactivity of the PDOs, and patients' disease progression will be analyzed to identify whether specific subpopulations of tumor‐infiltrating immune cells could be predictive factors of the disease outcomes. The comparison of molecular profiles, in vitro response to drugs, and clinical‐pathological data will allow the definition of a pattern capable of predicting the response of the primary tumor for the identification of those patients who may benefit from specific treatment. Strengths and Limitations The results of our study could help to better understand the OC behavior, may have implications for the development of effective immunotherapy and targeted pharmacological therapies for epithelial OC in a personalized medicine perspective. This will be a monocentric trial with an involvement of only 43 patients, so further studies will need to confirm our results. Trial Registration The clinical trial has been registered at Clinical‐Trials.gov with the identifier NCT06272240 on 02/14/2024
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.
Early Postoperative Albumin and Neutrophil Dynamics for Risk Stratification After Cytoreductive Surgery in Ovarian Cancer: A Retrospective Multicenter Cohort Study
Background and Objectives: Serum albumin is a widely available and inexpensive biomarker that reflects nutritional status and physiological reserve. Hypoalbuminemia has been linked to poor postoperative outcomes in surgical oncology; however, its role in predicting early complications after cytoreductive surgery for ovarian cancer, as well as the potential contribution of systemic inflammatory indices in nutritionally preserved patients, remains incompletely understood. This study aimed to evaluate the predictive value of early postoperative serum albumin for early surgical complications and to explore whether inflammatory indices could offer additional prognostic information in patients with adequate albumin levels. Materials and Methods: We conducted a retrospective observational cohort study including patients undergoing cytoreductive surgery for ovarian cancer at two Italian tertiary referral centers between July 2023 and December 2025. Postoperative serum albumin was measured on the first postoperative day. Systemic inflammatory parameters were assessed using perioperative changes in neutrophils and composite indices. Early postoperative complications occurring within 30 days were recorded. Multivariable logistic regression analyses were performed, and subgroup analyses were conducted in patients with postoperative albumin ≥3 g/dL. Receiver operating characteristic (ROC) analysis was used to identify an optimal cutoff for significant inflammatory predictors. Results: A total of 121 patients were included, of whom 30 developed early postoperative complications. Patients with complications had significantly lower postoperative albumin levels than those without complications (median 2.75 vs. 3.09 g/dL; p < 0.001). In multivariable analysis, lower postoperative albumin independently predicted early complications (OR 0.26, 95% CI 0.06–0.86). In the subgroup of patients with preserved albumin levels (≥3 g/dL), a smaller postoperative neutrophil decline independently predicted complications (OR 1.56, 95% CI 1.12–2.70). A neutrophil drop cutoff of −1.15 × 103/dL showed good specificity (81.5%) and high negative predictive value (95.7%). Conclusions: Early postoperative serum albumin is a strong predictor of early surgical complications after cytoreductive surgery for ovarian cancer. In patients with preserved nutritional status, dynamic neutrophil changes provide additional prognostic information. Incorporating low-cost metabolic and inflammatory biomarkers may enhance early postoperative risk stratification and support more personalized patient management.
Simple hysterectomy versus radical hysterectomy in early-stage cervical cancer: A systematic review and meta-analysis
This systematic review (SR) and meta-analysis aims to compare the surgery-related results and oncological outcomes between SH and RH in patients with early-stage cervical cancer. We systematically searched databases including PubMed, Embase and Cochrane to collect studies that compared oncological and surgery-related outcomes between SH and RH groups in patients with stage IA2 and IB1 cervical cancer. A random-effect model calculated the weighted average difference of each primary outcome via Review Manager V.5.4. Seven studies comprising 6977 patients were included into our study. For oncological outcomes, we found no statistical difference in recurrence rate [OR = 0.88; 95% CI (0.50, 1.57); P = 0.68] and Overall Survival (OS) [OR = 1.23; 95% CI (0.69, 2.19), P = 0.48]. No difference was detected in the prevalence of positive LVSI and lymph nodes metastasis between the two groups. Concerning surgery-related outcomes, the comprehensive effects revealed that the bladder injury [OR = 0.28; 95% CI (0.08, 0.94), P = 0.04] and bladder disfunction [OR = 0.10; 95% CI (0.02, 0.53), P = 0.007] of the RH group were higher compared to the SH group. This meta-analysis suggested there are no significant differences in terms of both recurrence rate and overall survival among patients with stage IA2-IB1 cervical cancer undergoing SH or RH, while the SH group has better surgery-related outcomes. These data confirm the need to narrow the indication for RH in early-stage cervical cancer.
Ovarian cancer predisposition beyond BRCA1 and BRCA2 genes
Several genes associated with hereditary ovarian cancer have been discovered as a result of the work done with next generation sequencing. It is estimated that approximately 23% of ovarian carcinomas have a hereditary predisposition. The most common hereditary condition is represented by germline mutations in BRCA1 or BRCA2 genes that account for 20-25% of high grade serous ovarian cancer. A number of other hereditary ovarian cancers are associated with different genes, with a crucial role in the DNA damage response pathway, such as the mismatch repair genes in Lynch syndrome, TP53 in Li-Fraumeni syndrome, STK11 in Peutz-Jeghers syndrome, CHEK2, RAD51, BRIP1, and PALB2. The goal of this manuscript is to summarize the published data regarding the molecular pathways involved in the pathogenesis of non-BRCA related hereditary ovarian cancer and to provide a tool that might be useful in discussing risk assessment, genetic testing, prevention strategies, as well as clinical and therapeutic implications for patients with ovarian cancer.
Scar-Free Laparoscopy in BRCA-Mutated Women
Background and Objectives: BRCA 1 and 2 mutations have a cumulative risk of developing ovarian cancer at 70 years of 41% and 15%, respectively, while a cumulative risk of breast cancer by 80 years of age was 72% for BRCA1 mutation carriers and 69% for BRCA2 mutation carriers. The NCCN recommends risk-reducing salpingo-oophorectomy (RRSO), typically between 35 and 40 years, and upon completion of childbearing in BRCA1 mutation, while it is reasonable to delay RRSO for management of ovarian cancer risk until age 40–45 years in patients with BRCA2. In recent years there have been two main lines of evolution in laparoscopy. The former concerning the development of a single-site laparoscopic and the latter concerning the miniaturisation of laparoscopic instruments (mini/micro-laparoscopy). Materials and Methods: In this case report, we show our experience in prophylactic adnexectomy, on a mutated-BRCA patient, using the MiniLap® percutaneous surgical system. Results: This type of technique is safe and effective and does not require a particular learning curve compared to single-port laparoscopy. Conclusions: The considerable aesthetic advantage of the scars, we believe, albeit to a lesser extent, is useful to find in these patients burdened by an important stress load.
Levonorgestrel-releasing intra-uterine device alone for managing early-stage endometrial cancer and endometrial hyperplasia with atypia in patients unfit for surgery: the ENDOIUD study
This study aimed to clarify the role of levonorgestrel-releasing intra-uterine device as a stand-alone therapy in managing patients with endometrial atypical hyperplasia/endometrial cancer who are not suitable for surgery, through the evaluation of cause-specific survival and the control of vaginal bleeding. This is a retrospective, multi-center study conducted in 9 referral gynecologic centers in Italy. Data regarding the clinical and oncological outcomes of patients with endometrial atypical hyperplasia/endometrial cancer (International Federation of Gynecology and Obstetrics Stage I) were analyzed. Patients were judged unsuitable for surgery due to an American Society of Anesthesiologists score ≥3 and the presence of multiple severe co-morbidities and, therefore, triaged to receive levonorgestrel-releasing intra-uterine device alone. A total of 78 women were enrolled. Fifteen patients (19.2%) had a diagnosis of endometrial atypical hyperplasia, whereas the other 63 (80.8%) had endometrial cancer. The baseline hemoglobin levels averaged 11.6 (range; 6-16), increasing to 12.1 (range; 7.8-14.9) during follow-up after levonorgestrel-releasing intra-uterine device insertion (p = .003). No patient experienced any side effects, and bleeding control was rated as excellent in most patients. Median disease-free survival was 43 months (range; 5-120) and median overall survival was 45 months (range; 5-120). Levonorgestrel-releasing intra-uterine device alone is a safe and effective approach, showing no side effects, and a promising oncological outcome in women with early-stage endometrial atypical hyperplasia/endometrial cancer unfit for surgery. Future prospective studies are required to clarify how to select patient candidates for this therapy and how to predict response to levonorgestrel-releasing intra-uterine device.
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.
Application of novel algorithm on a retrospective series to implement the molecular classification for endometrial cancer
The study aimed to validate the Betella algorithm, focusing on molecular analyses exclusively for endometrial cancer patients, where molecular classification alters risk assessment based on ESGO/ESTRO/ESP 2020 guidelines. Conducted between March 2021 and March 2023, the retrospective research involved endometrial cancer patients undergoing surgery and comprehensive molecular analyses. These included p53 and mismatch repair proteins immunohistochemistry, as well as DNA sequencing for POLE exonuclease domain. We applied the Betella algorithm to our population and evaluated the proportion of patients in which the molecular analysis changed the risk class attribution. Out of 102 patients, 97 % obtained complete molecular analyses. The cohort exhibited varying molecular classifications: 10.1 % as POLE ultra-mutated, 30.3 % as mismatch repair deficient, 11.1 % as p53 abnormal, and 48.5 % as non-specified molecular classification. Multiple classifiers were present in 3 % of cases. Integrating molecular classification into risk group calculation led to risk group migration in 11.1 % of patients: 7 moved to lower risk classes due to POLE mutations, while 4 shifted to higher risk due to p53 alterations. Applying the Betella algorithm, we can spare the POLE sequencing in 65 cases (65.7 %) and p53 immunochemistry in 17 cases (17.2 %). In conclusion, we externally validated the Betella algorithm in our population. The application of this new proposed algorithm enables assignment of the proper risk class and, consequently, the appropriate indication for adjuvant treatment, allowing for the rationalization of the resources that can be allocated otherwise, not only for the benefit of settings with low resources, but of all settings in general.
Tumor Microenvironment in Ovarian Cancer
A detailed understanding of molecular mechanism of cancer genesis is fundamental to develop innovative and personalized therapies. The new frontier in biomedical research is represented by organoids, a three-dimensional cell culture system obtained from a tissue fragment that accurately reproduces the essential properties of the original tissue in vitro, which could provide a valuable model for explanation of ovarian cancers pathogenesis and will allow to predict the response to a specific therapy. With this research project, we expect to generate ovarian cancer organoids to characterize in vitro interactions and molecular pathway among tumor cells, immune cells, and resident microbiota (intratumoral bacteria and/or microbial-derived molecules).
