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"Ferrari, Filippo Alberto"
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Effects of transdermal versus oral hormone replacement therapy in postmenopause: a systematic review
by
Noventa, Marco
,
Mikuš, Mislav
,
Goldštajn, Marina Šprem
in
Breast cancer
,
Clinical trials
,
Hormone replacement therapy
2023
PurposeTo summarize available evidence comparing the transdermal and the oral administration routes of hormone replacement therapy (HRT) in postmenopausal women.MethodsWe performed a systematic review of the literature on multiple databases between January 1990 and December 2021. We included randomized controlled trials and observational studies comparing the transdermal and oral administration routes of estrogens for HRT in postmenopausal women regarding at least one of the outcomes of interest: cardiovascular risk, venous thromboembolism (VTE), lipid metabolism, carbohydrate metabolism, bone mineral density (BMD), and risk of pre-malignant and malignant endometrial lesions, or breast cancer.ResultsThe systematic literature search identified a total of 1369 manuscripts, of which 51 were included. Most studies were observational and of good quality, whereas the majority of randomized controlled trials presented a high or medium risk of bias. Oral and transdermal administration routes are similar regarding BMD, glucose metabolism, and lipid profile improvements, as well as do not appear different regarding breast cancer, endometrial disease, and cardiovascular risk. Identified literature provides clear evidence only for the VTE risk, which is higher with the oral administration route.ConclusionsAvailable evidence comparing the transdermal and oral administration routes for HRT is limited and of low quality, recommending further investigations. VTE risk can be considered the clearest and strongest clinical difference between the two administration routes, supporting the transdermal HRT as safer than the oral administration route.
Journal Article
Cold Knife Versus Carbon Dioxide for the Treatment of Preinvasive Cervical Lesion
2024
Background and Objectives: Cervical cancer (CC) represents a significant health concern worldwide, particularly for younger women. Cold knife (CK) conization and carbon dioxide (CO2) laser conization are two techniques commonly used to remove pre-invasive lesions, offering a potential curative intent in cases of incidental diagnosis of CC. This study aimed to assess the clinical implications and pathological outcomes of CK vs. CO2 laser conization for pre-invasive lesions. Materials and Methods: We retrospectively analyzed women who underwent CO2 or CK conization for high-grade preinvasive lesions (CIN2/3, CIS and AIS) between 2010 and 2022. Patient demographics, surgical details and pathological outcomes were collected. Pregnancy outcomes, including composite adverse obstetric rates, and oncological follow-up data, were also obtained. Results: In all, 1270 women were included; of them, 1225 (96.5%) underwent CO2, and 45 (3.5%) underwent CK conization. Overall, the rate of positive endocervical or deep margins was lower with CO2 laser compared to CK (4.3% vs. 13.3%, p = 0.015). Incidental CC was diagnosed in 56 (4.4%) patients, with 35 (62.5%) squamous and 21 (46.6%) adenocarcinomas. In a multivariate regression model, the relative risk for positive endocervical or deep margins is significantly greater in cases of incidental diagnosis of CC (p < 0.01). In cases of incidental diagnosis of CC, we found that the probabilities of having either positive endocervical or deep margins after CO2 laser or CK conization are similar, with a higher risk in case of adenocarcinoma lesion. Among women with CC, 42 (75%) opted for radical treatment, while 14 (25%) underwent a follow-up. Only one woman (7.1%) in the follow-up group, who had undergone CK conization, experienced a composite adverse obstetric outcome. No recurrences were observed after a median follow-up of 53 months. Conclusions: CO2 laser conization achieved a lower positive margin rate overall. CK and CO2 conization appear to be equivalent oncological options for incidental CC.
Journal Article
Minimally Invasive Surgery in the Management of Advanced Epithelial Ovarian Cancer: A Comprehensive Analysis of Current Evidence and Clinical Applications
by
Ceccaroni, Marcello
,
Bogani, Giorgio
,
Cuccu, Ilaria
in
Ascites
,
Cancer
,
Carcinoma, Ovarian Epithelial - surgery
2025
Background and Objectives: Advanced epithelial ovarian cancer (AEOC) often requires extensive cytoreductive surgery. Minimally invasive surgery (MIS), especially diagnostic laparoscopy, is increasingly used to assess resectability and guide treatment. This review aimed to evaluate the evidence on MIS in AEOC, focusing on its diagnostic and therapeutic roles in primary and interval debulking surgery (PDS and IDS), and its impact on perioperative and oncologic outcomes. Materials and Methods: A structured literature review was performed using PubMed, MEDLINE, Embase, Scopus, and the Cochrane Library, including studies published between January 2000 and June 2025. Eligible studies involved laparoscopic or minimally invasive cytoreduction in PDS or IDS, reporting surgical feasibility, perioperative results, and oncologic outcomes. Data were synthesized qualitatively due to heterogeneity across studies. Results: Observational studies indicate that diagnostic laparoscopy predicts resectability, reduces futile laparotomies, and improves patient selection for primary surgery. In selected patients, non-randomized cohorts of laparoscopic PDS report R0 resection rates up to 95%, with low morbidity and short hospital stays. In IDS after neoadjuvant chemotherapy, MIS has been associated with reduced blood loss, fewer complications, and faster postoperative recovery, while showing progression-free and overall survival comparable to laparotomy in retrospective series. Conversion to open surgery was generally reported in fewer than 10% of cases when stringent selection criteria were applied. Conclusions: Diagnostic laparoscopy is a valuable tool for accurate preoperative evaluation and surgical planning in EOC. MIS, particularly for IDS, appears to offer reduced morbidity and equivalent survival outcomes when performed in experienced centers, whereas its application in PDS remains investigational and should be reserved for highly selected cases. These conclusions are limited by the predominance of retrospective evidence and the heterogeneity in patient selection and surgical expertise.
Journal Article
Enhanced Recovery after Surgery (ERAS) in Gynecology: State of the Art and the Problem of Barriers
by
Majd, Hooman Soleymany
,
Cisotto, Francesca
,
Ferrari, Federico
in
Clinical medicine
,
Collaboration
,
Colorectal surgery
2023
Objectives: The advantages of the enhanced recovery after surgery (ERAS) protocols application in all surgical branches have been largely demonstrated, even though there is a lack of a strong evidence from randomized trial and the evidence regarding the multimodality treatments is of low grade. Moreover, the problem of the barriers to the implementation of these protocols in clinical practice remains an unsolved problem. Mechanism: We performed a narrative review reporting the main barriers and enablers on the subject. Finding in Brief: The main barriers are resistance to change, lack of support from institutions and of financial resources or manpower, poor communication and collaboration within the multidisciplinary team, organizational problems, lack of standardized protocols, patient-related barriers (individual factors, reluctance, or inadequate education) and lastly clinical practice in small community hospitals. To overcome these problems, several enablers have been identified including: the involvement of the patient, the reorganization of care systems through standardized ERAS protocols, identification of a leader/coordinator, promotion of teamwork and staff education, financial resources, and the recognition of the role of the professionals involved. Conclusions: At this moment, resistance to change remains the most frequent and difficult barrier to overcome and, in our opinion, a reorganization of the health system aiming to the implementation of the ERAS protocols in the clinical practice is required.
Journal Article
Gut Microbiota Alterations and Reproductive Tract Dysbiosis in Endometriosis: A Systematic Review
by
Ceccaroni, Marcello
,
Uccella, Stefano
,
Baggio, Silvia
in
Citation management software
,
Data collection
,
Dysbiosis - complications
2026
Background and Objectives: Endometriosis is a chronic, estrogen-dependent inflammatory disease with multifactorial pathogenesis. Increasing evidence suggests that alterations in the gut and reproductive tract microbiota may contribute to disease development, progression, and associated symptoms through immune, hormonal, and metabolic mechanisms. This systematic review aimed to synthesize current human evidence on microbiota composition and function in women with endometriosis. Materials and Methods: A systematic literature search was conducted according to PRISMA 2020 guidelines across PubMed, Embase, Web of Science, Scopus, and the Cochrane Library. Observational human studies published in English between January 2015 and September 2025 evaluating gut, vaginal, cervical, endometrial, or peritoneal microbiota in women with endometriosis were included. Two reviewers independently screened studies, extracted data, and performed a qualitative synthesis due to methodological heterogeneity. Results: Nineteen studies were included, encompassing gut and reproductive tract samples analyzed primarily by 16S rRNA sequencing. Across cohorts, endometriosis was consistently associated with microbial dysbiosis characterized by enrichment of Proteobacteria and Firmicutes and depletion of Bacteroidetes, Lactobacillus, and Bifidobacterium. Increased abundance of opportunistic taxa, particularly Escherichia coli, Streptococcus, and Klebsiella, was frequently reported. Functionally, dysbiosis was linked to increased β glucuronidase activity, enhanced estrogen enterohepatic recirculation, reduced short-chain fatty acid production, and activation of pro-inflammatory immune pathways. Several studies reported correlations between microbial profiles, disease stage, pelvic pain, and infertility. Conclusions: Current evidence supports a reproducible association between gut microbiota dysbiosis and endometriosis. Altered microbial composition and function may contribute to chronic inflammation, hormonal imbalance, and disease persistence. Longitudinal and multi-omic studies are needed to clarify causality and to evaluate microbiota-based diagnostic and therapeutic strategies.
Journal Article
Robotic surgery for deep-infiltrating endometriosis: is it time to take a step forward?
2024
Endometriosis is a chronic debilitating disease that affects nearly 10% of women of the reproductive age. Although the treatment modalities of endometriosis are numerous, surgical excision of the endometriotic implants and nodules remains the sole cytoreductive approach. Laparoscopic excision of endometriosis was proven to be beneficial in improving the postoperative pain and fertility. Moreover, it was also proved to be safe and efficient in treating the visceral localization of deep endometriosis, such as urinary and colorectal endometriosis. More recently, robotic-assisted surgery gained attention in the field of endometriosis surgery. Although the robotic technology provides a 3D vision of the surgical field and 7-degree of freedom motion, the safety, efficacy, and cost-effectiveness of this approach are yet to be determined. With this paper, we aim to review the available evidence regarding the role of robotic surgery in the management of endometriosis along with the current practices in the field.
Journal Article
No Increased Risk of Autoimmune Diseases Following HPV Vaccination: A Systematic Review and Meta-Analysis
by
Ceccaroni, Marcello
,
Perniola, Giorgia
,
Ciminello, Enrico
in
Adjuvants
,
Anogenital
,
autoimmune disease
2025
Background: HPV vaccination reduces the risk of anogenital warts, high-grade cervical intraepithelial neoplasia (CIN2+), and cervical cancer. To enhance immunogenicity, HPV vaccines include adjuvants such as toll-like receptor agonists, which may theoretically trigger autoimmune responses. However, existing data on this risk remain conflicting. This systematic review and meta-analysis assess the association between HPV vaccination and autoimmune disease onset in post-licensure controlled studies. Methods: A comprehensive literature search was conducted in Scopus, PubMed/MEDLINE, ScienceDirect, and the Cochrane Library from inception to June 2024, following PRISMA guidelines. The study protocol was registered in PROSPERO (CRD42024606834). Results: A total of 356 studies were identified, including cross-reference reviews. Fourteen met inclusion criteria for qualitative and quantitative analysis, encompassing 8,088,838 patients, of whom 2,041,865 received the HPV vaccine. Conclusions: This meta-analysis found no significant association between HPV vaccination and autoimmune disease development. However, further large-scale observational studies are needed, particularly among male recipients, as current evidence is predominantly based on female populations. Future research should also evaluate risks for specific autoimmune disorders to refine the vaccine’s safety profile.
Journal Article
Real World Application of Chemotherapy Response Score in High Grade Serous Cancer of the Ovary
by
Cisotto, Francesca
,
Gambino, Angela
,
Ferrari, Federico
in
Chemotherapy
,
Cytokeratin
,
Demographics
2022
Background: High grade serous cancers (HGSC) of gynecological origin can be treated with neoadjuvant chemotherapy (NACT) and subsequent interval debulking surgery (IDS) when upfront surgery is not feasible. Chemotherapy response score (CRS) was proposed to evaluate on pathological specimens at IDS the response to NACT. Objective: We aim to assess survival outcomes stratified by CRS in HGSC patients and to explore interaction with residual disease (RD) after surgery. Methods: We identified all consecutive patients with HGSC at advanced stage (FIGO III–IV) that underwent NACT and IDS. We collected baseline data as well as survival data such as disease-free survival (DFS) and overall survival (OS). CRS was assessed on adnexal and omental specimens based on a three-tier classification. We conducted multivariate cox regression analyses of CRS classifications (CRS 1 vs 2 vs 3, CRS 1+2 vs 3 and CRS 1 vs 2+3) using RD as covariate. Results: We enrolled 47 patients with a median follow-up of 25 months (IQR: 11–78). RD after IDS failed to correlate with DFS (p = 0.73) and OS (p = 0.93). Adnexal CRS 2 (HR 0.4; 95% CI 0.2–1.0; p = 0.05) and CRS 3 (HR 0.30; 95% CI 0.11–0.65; p = 0.04) correlated with longer DFS. Moreover, CRS 2 (HR 0.12; 95% CI 0.04–0.33; p < 0.01) and CRS 3 (HR 0.06; 95% CI 0.02–0.20; p <0.01) on adnexal specimens were significantly associated with improved OS. Neither the omental three-tier nor the two-tier classifications correlated with DFS and OS. Conclusions: CRS classification is apparently a simple and reproducible method. In our study the adnexal three-tier system correlate with DFS and OS independently from RD at IDS. Further studies are needed to clarify the clinical role of CRS classification.
Journal Article
Vaginal “tunnel flap” technique for urethral neomeatus reconstruction after distal urethrectomy in advanced vulvar cancer: a case report with anatomical insights
by
Ceccaroni, Marcello
,
Bruni, Francesco
,
Masini, Gaia
in
Catheters
,
Clitoris
,
Connective tissue
2025
Vulvar cancer with distal urethral involvement requires radical surgery that can severely impact urinary function and quality of life. Urethral neomeatus reconstruction therefore, represents a critical yet underexplored challenge in gynecologic oncology. We report a novel vaginal “tunnel flap” technique designed to recreate a functional urethral outlet after radical vulvectomy and distal urethrectomy. The flap leverages detailed knowledge of the urethrovaginal septum and its vascular supply to create a well-vascularized mucosal tunnel that reproduces native urethral morphology while minimizing suture line tension and the risk of postoperative stenosis. In the presented case report, despite early wound-healing complications, suprapubic urinary diversion enabled complete recovery. Long-term follow-up showed sustained oncologic control, excellent urinary function, preserved sexual activity, and satisfactory aesthetic results. This report highlights the role of precise surgical anatomy in optimizing reconstructive outcomes and proposes a reproducible technique that balances oncologic safety with functional and aesthetic preservation.
Journal Article
2022-RA-1535-ESGO Uterine PEComa and prognostic value of the proposed classification systems: a retrospective study, systematic review, and metanalysis
by
Zorzato, Piercarlo
,
Uccella, Stefano
,
Franchi, Massimo
in
Classification
,
Miscellaneous
,
Systematic review
2022
Introduction/BackgroundPerivascular epithelioid cell tumors (PEComas) is a rare subtype of mesenchymal tumors composed of perivascular epithelioid cells. The main concern after the diagnosis is predicting the disease behavior: four classification systems have been proposed for this purpose based on size, pathological characteristics, and immunohistochemical characteristics.MethodologyWe retrospectively reviewed the prospectively collected pathologic registry to identify all cases of uterine PEComa diagnosed and treated at our center. Moreover, we conducted a systematic review of the literature to identify all published cases of uterine PEComa pathologically confirmed. For each identified case with available data, we applied all the proposed classification systems (FOLPE, FOLPE modified, Bennet, and Schoolmester) and assessed their performance with cox regression analysis.Abstract 2022-RA-1535-ESGO Figure 1Recurrence-free survival Kaplan meier curves. A: Folpe system; B: Folpe modified system; C: Schoolmester system; D: Bennet systemAbstract 2022-RA-1535-ESGO Figure 2Cause-specific death Kaplan meier curves. A: Folpe system; B: Folpe modified system; C: Schoolmester system; D: Bennet systemResultsWe identified seven cases of uterine PEComa diagnosed and treated at our center. The search strategy identified 51 papers for a total of 121 cases of uterine PEComa.The uterine corpus was the most frequent localization (n=55; 45.7%), and uterine bleeding was the clinical presentation in 36 (32.5%) cases. In most cases, the diagnosis was at the final pathological examination (n=39; 83%). Among those who recurred or dead due to disease, the median time to recurrence was 18 (2–82; IQR 4–21.7) months and the median time to death was 17.5 (5–43; IQR 12–35) months. The malignant group reported a higher rate of recurrence and cause-specific death than the benign group in all classifications. The Bennet system (figure 1–2) reported the highest HR for relapse and death due to PEComa in the malignant group versus the benign group (HR 14.17; 95% CI 4.29 – 46.72 for relapse; HR 33.17, 95% CI 4.39 – 4246.79 for death).ConclusionPreoperative diagnosis of uterine PEComa is uncommon without specific clinical presentation. Among proposed classification systems, the Bennet system reported the highest ability to distinguish between benign and malignant behaviors.
Journal Article