Luigi Della Corte

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.

Hereditary Women’s Cancer: Management and Risk-Reducing Surgery

Hereditary women’s syndromes due to inherited mutations result in an elevated risk of developing gynecological cancers over the lifetime of affected carriers. The BRCA 1 and 2 mutations, Lynch syndrome (LS), and mutations in rare hereditary syndromes increase this risk and require more effective management of these patients based on surveillance and prophylactic surgery. Patients need counseling regarding risk-reducing surgery (RRS) and the time required to perform it, considering the adverse effects of premenopausal surgery and the hormonal effect on quality of life, bone density, sexual activity, and cardiological and vascular diseases. Risk-reducing salpingo-oophorectomy (RRSO) is the gold standard for BRCA-mutated patients. An open question is that of endometrial cancer (EC) risk in patients with BRCA1/2 mutation to justify prophylactic hysterectomy during RRSO surgical procedures. RRS provides a 90–95% risk reduction for ovarian and breast cancer in women who are mutation carriers, but the role of prophylactic hysterectomy is underinvestigated in this setting of patients. In this review, we evaluate the management of the most common hereditary syndromes and the benefits of risk-reducing surgery, particularly exploring the role of prophylactic hysterectomy.

Fertility‐Sparing Approach in Patients with Endometrioid Endometrial Cancer Grade 2 Stage IA (FIGO): A Qualitative Systematic Review

Background. Endometrial cancer (EC) is one of the most common gynecologic malignancy, mostly in postmenopausal women. The gold standard treatment for EC is surgery, but in the early stages, it is possible to opt for conservative treatment. In the last decade, different clinical and pathological markers have been studied to identify women who respond to conservative treatment. A lot of immunohistochemical markers have been evaluated to predict response to progestin treatment, even if their usefulness is still unclear; the prognosis of this neoplasm depends on tumor stage, and a specific therapeutic protocol is set according to the stage of the disease. Objective. (1) To provide an overview of the conservative management of Stage 1A Grade (G) 2 endometrioid EC (FIGO) and the oncological and reproductive outcomes related; (2) to describe the molecular alterations before and after progestin therapy in patients undergoing conservative treatment. Materials and Methods. A systematic computerized search of the literature was performed in the main electronic databases (MEDLINE, Embase, Web of Science, PubMed, and Cochrane Library), from 2010 to September 2021, in order to evaluate the oncological and reproductive outcomes in patients with G2 stage IA EC who ask for fertility‐sparing treatment. The expression of several immunohistochemical markers was evaluated in pretreatment phase and during the follow‐up in relation to response to hormonal therapy. Only scientific publications in English were included. The risk of bias assessment was performed. Review authors’ judgments were categorized as “low risk,” “high risk,” or “unclear risk” of bias. Results. Twelve articles were included in the study: 7 observational studies and 5 case series/reports. Eighty‐four patients who took progestins (megestrol acetate, medroxyprogesterone acetate, and/or levonorgestrel‐releasing intrauterine devices) were analyzed. The publication bias analysis turned out to be “low.” 54/84 patients had a complete response, 23/84 patients underwent radical surgery, and 20/84 had a relapse after conservative treatment. Twenty‐two patients had a pregnancy. The length of follow‐up was variable, from 6 to 142 months according to the different studies analyzed. Several clinical and pathological markers have been studied to identify women who do not respond to conservative treatment: PR and ER were the most studied predictive markers, in particular PR appeared as the most promising; MMR, SPAG9, Ki67, and Nrf2‐survivin pathway provided good results with a significant association with a good response to progestin therapy. However, no reliable predictive markers are currently available to be used in clinical practice. Conclusions. The conservative treatment may be an option for patients with stage IA G2 EEC who desire to preserve their fertility. The immunohistochemical markers evaluation looks promising in predicting response to conservative treatment. Further large series and randomized clinical trials are needed to confirm these results.

Novel diagnostic approaches to intrauterine neoplasm in fertile age: sonography and hysteroscopy

Endometrial carcinoma (EC) is the most common gynecological malignancy in the world. It is mostly detected in postmenopausal women, but it can also occur in women of fertile age who need fertility-sparing therapy. An early diagnosis is the main objective for the correct management of these patients, making it possible to use a fertility-sparing treatment approach without exposing the patients to the risk of cancer progression. In this review, we discuss the role of sonography and hysteroscopy in the detection of intrauterine neoplasm in women of childbearing age.

Meigs Syndrome and Elevated CA-125: Case Report and Literature Review of an Unusual Presentation Mimicking Ovarian Cancer

Background and Objectives: Meigs syndrome is represented by a benign adnexal tumor, ascites, and hydrothorax. Even though the ovarian mass is often characterized by a fibroma-like origin, cancer antigen-125 (CA-125) serum levels could be elevated as in the development of ovarian cancer. Here, we present the case of a patient with Meigs syndrome and increased CA-125. Materials and Methods: We performed systematic research for articles including similar cases in PubMed, EMBASE, and Scopus in February 2023, adopting the string of idioms: “Meigs syndrome AND Cancer antigen 125”, and following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Results: Eligible records were 25. Hydrothorax was right-sided in 10 cases over 25; left-sided in two patients over 25. Concerning ascites, two patients showed more than 6 L of ascitic fluid, whereas three patients had 6 L or less. CA-125 elevation ranged from 149 IU/mL to 3803 IU/mL. Adnexal mass histotypes were: struma ovarii (12 cases), thecomas (two cases), fibrothecomas (five cases), fibromas (five cases), and one sclerosing stromal tumor (SST). Conclusions: In postmenopausal women with elevated CA-125 serum levels and an adnexal mass suspicious for malignancy at ultrasound (US), ascites and pleural effusion, surgery, and histopathological examination are necessary. MS is a diagnostic option, with an excellent prognosis after exeresis of the mass.

Scoring systems for the evaluation of adnexal masses nature: current knowledge and clinical applications

Adnexal masses are a common finding in women, with 20% of them developing at least one pelvic mass during their lifetime. There are more than 30 different subtypes of adnexal tumours, with multiple different subcategories, and the correct characterisation of the pelvic masses is of paramount importance to guide the correct management. On that basis, different algorithms and scoring systems have been developed to guide the clinical assessment. The first scoring system implemented into the clinical practice was the Risk of Malignancy Index, which combines ultrasound evaluation, menopausal status, and serum CA-125 levels. Today, current guidelines regarding female patients with adnexal masses include the application of International Ovarian Tumours Analysis simple rules, logistic regression model 1 (LR1) and LR2, OVERA, cancer ovarii non-invasive assessment of treating strategy, and assessment of Different Neoplasias in the adnexa. In this scenario, the choice of the scoring system for the discrimination between benign and malignant ovarian tumours can be complex when approaching patients with adnexal masses. This review aims to summarise the available evidence regarding the different scoring systems to provide a complete overview of the topic.

Poly (ADP-ribose) polymerase (PARP) as target for the treatment of epithelial ovarian cancer: what to know

Poly (ADP-ribose) polymerase (PARP) inhibitors are being developed in maintenance and recurrence treatment settings of epithelial ovarian cancers (EOCs) with BRCA 1-2 gene mutation. PARP inhibitors are the first example of drugs targeting the loss of a gene suppressor: they block base-excision repair in the cancer cells, which have lost homologous recombination due to BRCA-mutation, resulting in loss of DNA repair and cell death, also known as synthetic lethality. This article provides an overview of PARP inhibitors in OC treatment and also an extensive section on the combined strategies of PARP inhibitors, including approved as well as currently investigated drugs. It also offers a section on the use of predictive biomarkers for PARP inhibitors treatment. Ongoing trials, including novel combinations, are discussed. In recent years, there is increasing evidence that PARP inhibitor therapy can have life-long percussion in the treatment of EOC, even if some questions have to be solved yet, such as its use in combination therapy, the possibility to retreat with a PARP inhibitor, and finally how to overcome a resistance mechanism to this therapy. In this way, PARP inhibitors can obtain an important role in making a personalized therapeutic program in the case of first-line, neoadjuvant, platinum-sensitive, and resistant high-grade serous OC treatment.

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.

Advances in paclitaxel combinations for treating cervical cancer

Cervical cancer is the fourth common cancer in women worldwide. While, in the past, locally advanced stage disease was treated by pelvic radiotherapy, nowadays the National Cancer Institute strongly recommends chemoradiation protocols. Weekly cisplatin was previously the standard of care in this setting; however, the low response rate and the short median progression-free survival (PFS) of patients have led researchers to investigate combinatory regimens. This article is based on literature searches up until April 2019, with current trial registers also analyzed. All data available on this topic has been summarized in this narrative review. In recent years, it has been demonstrated that cisplatin-based doublets, and in particular, cisplatin plus paclitaxel, are superior to cisplatin as a monotherapy in terms of response rate and progression-free survival of patients with advanced cervical cancer. This double regime combined with bevacizumab is also considered the first-line option for metastatic or recurrent disease. Dose-dense paclitaxel in neo-adjuvant chemotherapy combinations is a promising option in patients with locally advanced cervical cancer. Exploration of novel biological therapies and

Immunohistochemical and serum profile of squamous cell carcinoma of the vulva: The Dual Vulvar Panel (DVP) project

This study aimed to evaluate the expression of selected immunohistochemical (IHC) markers and serum squamous cell carcinoma antigen (SCC-Ag) in vulvar squamous cell carcinoma (VSCC), and to investigate associations with recurrence and death using molecular clustering and diagnostic performance analyses. This single-centre prospective study included 27 patients with histologically confirmed VSCC. Tumour specimens were assessed for expression of p16, p53, programmed death-ligand 1 (PD-L1), CD44 and epidermal growth factor receptor (EGFR). Serum SCC-Ag was measured and correlated with clinical outcomes. Statistical analyses comprised Pearson's correlation, logistic regression, receiver operating characteristic curve analysis, diagnostic performance metrics, and unsupervised hierarchical clustering integrating IHC and SCC-Ag data. No significant associations were observed between individual IHC markers and clinical outcomes. Serum SCC-Ag showed a positive trend towards association with recurrence (r = 0.462; p = 0.071), with an increased odds ratio (OR) (OR = 2.7). When analysed as a binary variable, SCC-Ag demonstrated sensitivity of 50%, specificity of 76%, and overall accuracy of 70%. As a continuous variable, SCC-Ag achieved an area under the curve value of 0.83. The combination of SCC-Ag and p53 improved sensitivity to 83% and negative predictive value to 89%. Unsupervised hierarchical clustering identified three biological subgroups, with the cluster characterized by high SCC-Ag and EGFR expression and low p16 expression associated with recurrence more frequently. Serum SCC-Ag showed superior prognostic performance compared with individual IHC markers, and may be useful for postoperative risk stratification in VSCC. Combined biomarker panels, including p53, PD-L1, EGFR and p16, yielded promising sensitivity, supporting future strategies.

The role of endocervicoscopy in women with cervical intraepithelial neoplasia: a systematic review of the literature

Endocervicoscopy is an alternative diagnostic tool to endocervical curettage for the diagnostic workup of repeatedly positive cervicovaginal cytology suggestive of a high-grade squamous intraepithelial lesion (HSIL) and negative or unsatisfactory colposcopy. The aim of this review is to summarize the current evidence on the diagnostic accuracy of endocervicoscopy in women with cervical intraepithelial neoplasia in the presence of nonvisible squamocolumnar junction with unsatisfactory colposcopy. A systematic review of literature was performed by searching in the main electronic databases (MEDLINE, EMBASE, Web of Science, Scopus, ClinicalTrial.gov, OVID and Cochrane Library), from their inception to January 2021 for studies testing endocervicoscopy. Risk of Bias Assessment was performed. Four articles were included: three prospective and one retrospective cohort studies. Data on the endocervicoscopy accuracy, the accuracy and reliability correlation with definitive histology, the cone biopsy dimension after endocervicoscopy, the comparison between endocervicoscopy and curettage and the lesion missed were analyzed. Based on our results, the limit of this technique is the low predictive value that does not allow it to replace the colposcopy. Nevertheless, it could help to define the characteristics and localization of cervical-suspected lesions. However, further studies are needed to clarify its use and indication.

How endocervicoscopy can impact obstetric outcomes in women undergoing LEEP for CIN2 + : a retrospective cohort analysis

To assess the impact of preoperative endocervicoscopy on obstetric outcomes and complications in women undergoing LEEP for CIN2 + . This was a retrospective cohort study carried out between October 2012 and April 2018. All women had undergone cervical length measurement at T0 (before LEEP), T1 (6 months after LEEP), and T2 (at 20 weeks of pregnancy) through transvaginal ultrasound examination after LEEP for CIN2 + . A total of 528 patients fulfilled our inclusion criteria and contributed to the final analysis: 288 had undergone endocervicoscopy before the excisional procedure (Group A), while the remaining 240 (Group B) did not. Patients who did not undergo endocervicoscopy showed a greater amount of tissue excised at LEEP compared to those of Group A (6.7% vs 31.9% in Group A and B, p < 0.01, respectively). A statistically relevant difference was detected in the lesion margins involvement: negative in 93.8% in Group A compared to 65.6% in Group B. The cervicometry before the treatment resulted in similar between the two groups, while a statistically significant difference was noted after 6 months (37.5 ± 2.9 mm in Group A vs 35.1 ± 3.8 mm in Group B, p < 0.01) and at 20th week pregnancy (36.9 ± 5.3 mm in Group A vs 33.5 ± 5.6 mm in Group B, p < 0.01). The number of pregnancies after LEEP as well as the difference in the elapsed time (in months) did not result in a statistical significance between the two groups. The threatened preterm labor (TPL) and the threatened miscarriage showed a statistically significant difference in incidence between the two groups (4,2% and 4.2% in Group A vs 15.3% and 25% in Group B, p < 0.01, respectively). Endocervicoscopy reduces the size of the LEEP sample and in particular its depth, saving healthy cervical tissue, and guarantees the total eradication of the lesion as the resection margins are negative in almost all cases, allowing for a reduction of the rate of TPL and threatened miscarriage in women with CIN2 + , especially with Type 2 or 3 cervical squamocolumnar junction (SCJ).

A comparative retrospective analysis on robot-assisted laparoscopic surgery compared to conventional laparoscopy in case of myomectomy: experience in a third-level hospital of Southern Italy

AbstractUterine myomas are the most common gynecological disease in reproductive-aged women, present several symptoms, and require effective medical and/or surgical strategies. This study aimed to compare robotic-assisted laparoscopic myomectomy (RALM) with laparoscopic myomectomy (LM) in terms of operative times, intraoperative estimated blood loss, pre- and post-hemoglobin levels drop, and length of hospital stay. Data from 50 clinical records (25 RALM in Group A and 25 LM in Group B) of patients with uterine fibroids were collected from December 2022 to December 2023 at Gynecological Unit of DAI Materno-Infantile Federico II in Naples, Italy. Patients aged 30–49 years with symptomatic fibroids were included. Data on peri-operative outcomes, including operative time for myomectomy (OTM), overall operative time (OOT), intraoperative estimated blood loss (EBL), pre- and post-operative hemoglobin levels, and length of hospital stay were analyzed. The OTM in the presence of &gt; 5 myomas was 59 [52–65] vs 69 min [61–96] (p &lt; 0.001) for RALM and LM groups, respectively. Moreover, also in presence of ≤ 5 myomas, a difference was observed in the RALM group 48[43–55] compared to the LM group 53[50–61] min (p = 0.07). The OOT was also statistically significant for Group A compared to Group B (83[65–93] vs 72[56–110] min, p &lt; 0.001). There were no significant differences between the two groups in terms of pre- and post-operative hemoglobin levels and EBL (p = 0.178). Group A demonstrated a notably shorter hospital stay 1.2 [1–2] days compared to Group B 2.9[3–3.75] days (p = 0.007). Our study suggests potential advantages of RALM over LM in terms of reduced operative times and shorter hospital stays. The standardized approach and extensive surgical experience likely contributed to the favorable outcomes of RALM.

C-section technique vs minilaparotomy after minimally invasive uterine surgery: a retrospective cohort study

Abstract Purpose Uterine leiomyomas are benign uterine tumors. The choice of surgical treatment is guided by patient's age, desire to preserve fertility or avoid "radical" surgical interventions such as hysterectomy. In laparotomy, the issue of extracting the fibroid from the cavity does not arise. However, in laparoscopy and robotic surgery, this becomes a challenge. The aim of the present study was to determine the optimal surgical approach for fibroid extraction following laparoscopic or robotic myomectomy in terms of postoperative pain, extraction time, overall surgical time, scar size, and patient satisfaction. Methods A total of 51 patients met the inclusion criteria and were considered in our analysis: 33 patients who had undergone the "ExCITE technique" (Group A), and 18 patients a minilaparotomy procedure (Group B), after either simple myomectomy, multiple myomectomy, supracervical hysterectomy, or total hysterectomy. The diagnosis of myoma was histologically confirmed in all cases. Results Regarding the postoperative pain evaluation, at 6 h, patients reported 4 [3–4] vs 6 [5.3–7] on the VAS in Group A and B, as well as at 12 h, 2 [0–2] vs 3.5 [2.3–4] in Group A and B, respectively: both differences were statistically significant (p &lt; 0.001). No statistically significant difference at 24 h from surgery was found. All patients in Group A were satisfied with the ExCITE technique, while in Group B only 67% of them. The length of the hospital stay was significantly shorter in Group A as compared to Group B (p = 0.007). In terms of the operative time for the extraction of the surgical specimen, overall operative time, and the scar size after the surgery, there was a statistically significant difference for those in Group A. Conclusion The ExCITE technique does not require specific training and allows the surgeon to offer a minimally invasive surgical option for patients, with also an aesthetic result. It is a safe and standardized approach that ensures tissue extraction without the need for mechanical morcellation.