Matteo Marchetti

The Impact of Neoadjuvant Chemotherapy on Ovarian Cancer Tumor Microenvironment: A Systematic Review of the Literature

Immunotherapy, particularly the use of immune checkpoint inhibitors (ICIs), has shown limited efficacy in treating ovarian cancer (OC), possibly due to diverse T cell infiltration patterns in the tumor microenvironment. This review explores how neoadjuvant chemotherapy (NACT) impacts the immune landscape of OC, focusing on tumor-infiltrating lymphocytes (TILs), PD-1/PD-L1 expression, and their clinical implications. A comprehensive literature search across four databases yielded nine relevant studies. These studies evaluated stromal (sTILs) and intra-epithelial (ieTILs) TILs before and after NACT. sTIL responses varied, impacting prognostic outcomes, and ieTILs increased in some patients without clear survival associations. PD-L1 expression after NACT correlated with improved overall survival (OS), and increases in granzyme B+ and PD-1 correlated with longer progression-free survival (PFS). Remarkably, reduced FoxP3+ TILs post-NACT correlated with better prognosis. NACT often increases sTIL/ieTIL and CD8+ subpopulations, but their correlation with improved PFS and OS varies. Upregulation of co-inhibitory molecules, notably PD-L1, suggests an immunosuppressive response to chemotherapy. Ongoing trials exploring neoadjuvant ICIs and chemotherapy offer promise for advancing OC treatment. Standardized measurements assessing TIL density, location, and heterogeneity are crucial for addressing genetic complexity and immunological heterogeneity in OC.

Peritonectomy and resection of mesentery during Visceral-Peritoneal Debulking (VPD) in patients with stage IIIC-IV ovarian cancer: A phase I-II trial

To describe the surgical technique, assess feasibility, efficacy, and safety of peritonectomy and/or resection of mesentery (P-Rme) during Visceral-Peritoneal Debulking (VPD) in patients with stage IIIC-IV ovarian cancer (OC). In April 2009 we registered a protocol study on the safety and feasibility of P-Rme. In the period April 2009-December 2022, 687 patients with FIGO stage IIIC-IV ovarian cancer underwent VPD. One hundred and twenty-nine patients (18.7%) had extensive disease on the mesentery and underwent P-Rme. Feasibility was assessed as the number of procedures completed. Efficacy was measured as the rate of Complete Resection (CR). Safety was defined by the intra- and post-operative morbidity rate specifically associated with these procedures. In all patients P-Rme was successfully completed. P-me was performed in 82 patients and R-me in 47, both procedures in 23 patients. CR was achieved in all 129 patients with an efficacy of 100%. Intra-operatively 5 patients out of 129 experienced small bowel loop surgical devascularization. They required small bowel resection and anastomosis. The procedure specific morbidity was 3.8%. No post-operative complication was related to P-Rme. At 64 months median follow-up, survival outcomes in the study group were similar to patients in the control group. Overall, almost 20% of the VPD patients needed P-Rme to obtain a CR. P-Rme was a safe and effective step during VPD. The rate of CR in the study group was 100% achieved thanks to the addition of the P-Rme. No procedure specific post-operative complications occurred but 3.8% of the patients had unplanned additional surgery related to these procedures.

Feasibility of laparoscopic Visceral-Peritoneal Debulking (L-VPD) in patients with stage III–IV ovarian cancer: the ULTRA-LAP trial pilot study

A non-randomized prospective clinical trial (ULTRA-LAP) was registered to test safety, side effects and efficacy of laparoscopic Visceral-Peritoneal Debulking (L-VPD) in patients with stage III-IV ovarian cancer (OC). A pilot study was designed to identify which OC patients are suitable to undergo L-VPD. Between March 2016 and October 2021, all consecutive patients with OC underwent exploratory laparoscopy (EXL). All patients whose disease was deemed amenable for a complete resection (CR) at imaging review and EXL, underwent VPD. In all patients a consistent attempt was made at completing L-VPD. Two hundred and eight OC had EXL in the study period: 121 underwent interval VPD and 87 up-front VPD. Overall, 158 patients had VPD by laparotomy (75.9%) and 50 (24.1%) had L-VPD, of which 34 patients as interval (iL-VPD) and 16 as up-front (uL-VPD). Intra- and post-operative morbidity was very low in the L-VPD group. CR rate was 98% in L-VPD group and 94% in VPD. Most common reason for conversion was diaphragmatic disease extending dorsally. In the pilot study of ULTRA-LAP, L-VPD was completed in 24,1% of OC. Initial analysis supports the feasibility of L-VPD in 2 groups of OC: those with no gross disease at interval surgery and those with gross visible disease at upfront or interval surgery, but limited to: pelvis (including recto-sigmoid), gastro colic omentum, peritoneum and diaphragm, the latter not requiring dorsal liver mobilization. Both groups had 100% feasibility and have been thus forth recruited to ULTRA-LAP. ClinicalTrials.gov Identifier: NCT05862740.

Indocyanine green fluorescence angiography for bowel anastomosis assessment in ovarian cancer surgery

Optimizing bowel anastomotic integrity is a key consideration in ovarian cancer cytoreductive surgery, as anastomotic complications can significantly impact postoperative recovery and delay systemic treatment. Conventional assessment techniques like visual inspection and palpation are inherently subjective and may not consistently predict the likelihood of anastomotic leakage. Due to the serious consequences of anastomotic failure and the impact of diverting ostomies, there is growing interest in fluorescence-based technologies to enhance the diagnostic accuracy of anastomoses and support more informed intraoperative decision-making. Indocyanine green fluorescence angiography (ICG-FA) has emerged as a promising tool for improving the accuracy of bowel perfusion at the time of surgery. While widely adopted in general surgery, its use in gynecologic oncology is still growing and has not yet been established as the standard of care. By allowing surgeons to assess perfusion intraoperatively, ICG-FA may help reduce anastomotic leaks and decrease the need for diverting ostomies, with the goal of improving patient outcomes and quality of life. While early evidence indicates that ICG-FA is a safe and feasible tool in ovarian cancer surgery, additional research is required to develop standardized protocols and evaluate its clinical significance and long-term benefits. This review provides a technical overview, examines the current evidence surrounding ICG-FA in gynecologic oncology, explores its potential advantages and limitations, and highlights future directions for research in fluorescence-guided bowel anastomosis assessment.

Fertility-sparing vs hysterectomy for uterine STUMP: A pragmatic clinical study.

Uterine smooth muscle tumors of uncertain malignant potential (STUMP) are rare neoplasms with unpredictable clinical behavior. Optimal management, particularly in reproductive-aged women, remains controversial, with limited data comparing the safety of fertility-sparing versus hysterectomy. This multicentre retrospective cohort study included women aged 18-85 with histologically confirmed STUMP treated at 17 Italian gynecologic oncology centers from 2010 to 2023. Patients underwent either fertility-sparing surgery (myomectomy or hysteroscopic resection) or definitive surgery (hysterectomy ± salpingo-oophorectomy). Kaplan-Meier and Cox models were used to compare recurrence-free survival (RFS) and overall survival (OS). Median (range) follow-up was 51 (1-291) months. Among 401 women, 106 (26.4 %) received fertility-sparing treatment (mean [± SD] age: 35.3 ± 6.8 years) and 295 (73.6 %) underwent definitive surgery (mean [± SD] age: 47.7 ± 9.2). At total follow-up, recurrence occurred in 12.5 % of patients, predominantly within the pelvis. Median RFS was longer after definitive surgery than after fertility-sparing procedures (50.0 vs 42.5 months; HR 2.39 [95 % CI 1.36-4.19]), although this difference disappeared when benign (leiomyoma) recurrences were excluded (HR 1.74 [95 % CI 0.90-3.34]). At last available follow-up, 97.5 % of patients were alive, with no significant OS difference between treatment groups (HR 0.22 [95 % CI 0.27-1.79]). Outcomes were comparable across menopausal status and concurrent adnexal removal. Definitive surgery reduces recurrence risk, but long-term survival is similarly excellent after fertility-sparing surgery in appropriately selected women with STUMP. Conservative management represents a reasonable option for patients desiring fertility, provided they receive counseling regarding recurrence risk, diagnostic uncertainty, and the need for long-term surveillance.

Enhanced Recovery After Surgery (ERAS) in gynecologic surgery: hot topic debates at the 2025 ERAS World Congress

The Enhanced Recovery After Surgery pathway has transformed peri-operative care in gynecologic surgery through multi-disciplinary, evidence-based protocols. However, real-world adherence to and interpretation of specific Enhanced Recovery After Surgery elements remain heterogeneous, with ongoing discussion about their feasibility and clinical relevance. During the 2025 Enhanced Recovery After Surgery World Congress in Turin, Italy, a rapid-fire debate session addressed 4 "hot topics" in gynecologic Enhanced Recovery After Surgery implementation. Peri-operative dysglycemia is associated with worse surgical outcomes, although the evidence favors a targeted rather than universal screening strategy. Universal hemoglobin A1c testing was considered impractical, with screening recommended for patients with diabetes, obesity, or cardiovascular disease to balance safety and oncologic timeliness. Although transversus abdominis plane blocks reduce opioid use and prolong analgesia, multi-layer wound infiltration remains a pragmatic and cost-effective alternative, especially in low-resource settings where expertise or ultrasound guidance is limited. In light of the overall risk profile and low bleeding rates, many patients undergoing laparotomy for adnexal masses are likely to benefit from pharmacologic prophylaxis. Development of gynecology-specific risk models remains an unmet research priority. Structured multi-disciplinary warming bundles can significantly reduce peri-operative hypothermia, but implementation must remain flexible to accommodate different institutional resources and thresholds. The 2025 Enhanced Recovery After Surgery World Congress debates reinforced that the evolution of Enhanced Recovery After Surgery in gynecologic surgery depends less on discovering new interventions than on refining, validating, and implementing existing evidence. Individualized standardization-adapting Enhanced Recovery After Surgery principles to patient and resource variability-remains the cornerstone of enhanced recovery progress.

ULTRA-LAP Trial: Laparoscopic Debulking Surgery (LDS) in Advanced Ovarian Cancer

ULTRA-LAP is a prospective study is to investigate the safety, efficacy and feasibility of laparoscopic debulking surgery (LDS) for the treatment of patients with advanced ovarian cancer. The outcomes to measure are: * Safety: the rate of patients experiencing intra- and post-operative early and late morbidities (within the hospitalization and up to 60 days from surgery) * Efficacy: the rate of patients in which the surgical target set pre-operatively (complete resection) is achieved by laparoscopy. * Feasibility: the rate of patients who have their procedure completed by laparoscopy Patients will undergo laparoscopic debulking surgery (LDS) if the surgical target can be met. If it cannot be achieved by laparoscopy the surgeon will convert to laparotomy.