Oncological safety of hysteroscopy in endometrial cancer.

OBJECTIVE: It has been suggested that the manipulation of neoplastic tissue during hysteroscopy may lead to dissemination of tumor cells into the peritoneal cavity and worsen prognosis and overall survival. The goal of this study was to assess the oncological safety comparing hysteroscopy to Pipelle blind biopsy in the presurgical diagnosis of patients with endometrial cancer. METHODS: We performed a retrospective multicentric study among patients who had received primary surgical treatment for endometrial cancer. A multivariate statistical analysis model was used to compare relapse and survival rates in patients who had been evaluated preoperatively either by hysteroscopy or Pipelle biopsy. The relapse rate, disease-free survival, and overall survival were assessed as the main outcomes. The histological type, tumor size, myometrial invasion, International Federation of Gynecology and Obstetrics (FIGO) stage, surgical approach, use of a uterine manipulator, and adjuvant treatment were also included in the analysis. RESULTS: A total of 1731 women from 15 centers were included: 1044 in the hysteroscopy group and 687 in the Pipelle sampling group. 225 patients relapsed during the 10 year follow-up period: 139 (13.3%) in the hysteroscopy group and 86 (12.4%) in the Pipelle sampling group. There is no evidence of an association between the use of hysteroscopy as a diagnostic method and relapse rate (HR 1.24, 95% CI 0.92 to 1.66; p=0.16), lower disease-free survival (HR 1.23, 95% CI 0.92 to 1.66; p=0.15), or overall survival (HR 0.95, 95% CI 0.70 to 1.29; p=0.76). CONCLUSION: Hysteroscopy is a safe diagnostic method for patients with endometrial cancer with no impact on oncological outcomes when compared with sampling by Pipelle.

Impact of uterine manipulator on oncological outcome in endometrial cancer surgery.

BACKGROUND: There are limited data available to indicate whether oncological outcomes might be influenced by the uterine manipulator, which is used at the time of hysterectomy for minimally invasive surgery in patients with endometrial cancer. The current evidence derives from retrospective studies with limited sample sizes. Without substantial evidence to support its use, surgeons are required to make decisions about its use based only on their personal choice and surgical experience. OBJECTIVE: To evaluate the use of the uterine manipulator on oncological outcomes after minimally invasive surgery, for apparent early-stage endometrial cancer. STUDY DESIGN: We performed a retrospective multicentric study to assess the oncological safety of uterine manipulator use in patients with apparent early-stage endometrial cancer, treated with minimally invasive surgery. The type of manipulator, surgical staging, histology, lymphovascular space invasion, International Federation of Gynecology and Obstetrics stage, adjuvant treatment, recurrence, and pattern of recurrence were evaluated. The primary objective was to determine the relapse rate. The secondary objective was to determine recurrence-free survival, overall survival, and the pattern of recurrence. RESULTS: A total of 2661 women from 15 centers were included; 1756 patients underwent hysterectomy with a uterine manipulator and 905 without it. Both groups were balanced with respect to histology, tumor grade, myometrial invasion, International Federation of Gynecology and Obstetrics stage, and adjuvant therapy. The rate of recurrence was 11.69% in the uterine manipulator group and 7.4% in the no-manipulator group (P<.001). The use of the uterine manipulator was associated with a higher risk of recurrence (hazard ratio, 2.31; 95% confidence interval, 1.27-4.20; P=.006). The use of uterine manipulator in uterus-confined endometrial cancer (International Federation of Gynecology and Obstetrics [FIGO] I-II) was associated with lower disease-free survival (hazard ratio, 1.74; 95% confidence interval, 0.57-0.97; P=.027) and higher risk of death (hazard ratio, 1.74; 95% confidence interval, 1.07-2.83; P=.026). No differences were found regarding the pattern of recurrence between both groups (chi-square statistic, 1.74; P=.63). CONCLUSION: In this study, the use of a uterine manipulator was associated with a worse oncological outcome in patients with uterus-confined endometrial cancer (International Federation of Gynecology and Obstetrics I-II) who underwent minimally invasive surgery. Prospective trials are essential to confirm these results.

Image-guided brachytherapy in cervical cancer: Experience in the Complejo Hospitalario de Navarra.

PURPOSE: To evaluate dosimetric and clinical findings of MRI-guided HDR brachytherapy (HDR-B) for cervical carcinoma. MATERIAL AND METHODS: All patients had a CT, MRI and pelvic-paraaortic lymphadenectomy. Treatment: pelvic (+/-)para-aortic3D/IMRT radiotherapy (45 Gy), weekly cisplatin and HDR-B and pelvic node/parametrial boost 60 Gy until interstitial brachytherapy was done. Two implants: 2008-2011: 5 fractions of 6 Gy, 2011: 2016, 4 fractions of 7 Gy. MRI/TAC were done in each implant. The following were defined: GTV, CTH-HR, CTV-IR; OAR: rectum, bladder and sigmoid. RESULTS: From 2007 to 2016: 57 patients. Patients: T1b2-T2a: 4p, T2b 41p, T3a: 2p; T3B 8p T4a: 2p; N0: 32p, N1 21p, no lymphadenectomy: 4p. Median follow up: 74.6 m (16-122 m), recurrence: 5p local, 6p node, 9p metastasis and 37p without recurrence.Local control 5 years: 90.1%; Ib2-IIB: 94.8%, III-IVa: 72.2%. (p:0.01). RDFS 5y was 92.5%; IB2-IIB: 93%, III: 85% (p:0.024); for pN0: 100%; pN+ iliac-paraaortic: 71.4% (p: 0.007). MFS 5y was 84.1%. Overall survival (OS) at 5y: 66.6% and the cancer specific survival (CEOS) was 74%. Univariate analysis survival: stage Ib2-II 83% vs. III-IVa 41% (p = 0.001); histology: squamous 78%, adenocarcinoma 59.7% (p: ns); lymph node: N0 85% vs. PA+P- 72%, and PA+P+ 35% (p = 0.010). In relation with: HR-CTV dose > 85 Gy, CEOS: 82.5% vs. 77%, and volume CTV-HR < 30 cc: 81.8% and >30 cc: 67%; p: ns. Acute grade 2-3 toxicity: rectal 15.7%, intestinal 15.7% and vesical 15.5%. CONCLUSION: Use of interstitial HDR-BQ guided by RM increased CTV-HR dose and local control, like EMBRACE results. Nodal boost improves RDFS and perhaps OS.

Effectiveness of Nirsevimab Immunoprophylaxis Administered at Birth to Prevent Infant Hospitalisation for Respiratory Syncytial Virus Infection: A Population-Based Cohort Study.

Respiratory syncytial virus (RSV) infection is a frequent cause of hospitalisation in the first few months of life; however, this risk rapidly decreases with age. Nirsevimab immunoprophylaxis was approved in the European Union for the prevention of RSV-associated lower respiratory tract disease in infants during their first RSV season. We evaluated the effectiveness of nirsevimab in preventing hospitalisations for confirmed RSV infection and the impact of a strategy of immunisation at birth. A population-based cohort study was performed in Navarre, Spain, where nirsevimab was offered at birth to all children born from October to December 2023. Cox regression was used to estimate the hazard ratio of hospitalisation for PCR-confirmed RSV infection between infants who received and did not receive nirsevimab. Of 1177 infants studied, 1083 (92.0%) received nirsevimab. The risk of hospitalisation for RSV was 8.5% (8/94) among non-immunised infants versus 0.7% (8/1083) in those that were immunised. The estimated effectiveness of nirsevimab was 88.7% (95% confidence interval, 69.6-95.8). Immunisation at birth of infants born between October and December 2023 prevented one hospitalisation for every 15.3 immunised infants. Immunisation of children born from September to January might prevent 77.5% of preventable hospitalisations for RSV in infants born in 2023-2024. These results support the recommendation of nirsevimab immunisation at birth to children born during the RSV epidemic or in the months immediately before to prevent severe RSV infections and alleviate the overload of paediatric hospital resources.

Oncological outcomes of intraperitoneal chemotherapy in advanced ovarian cancer: BRCA mutation role.

INTRODUCTION: The knowledge of BRCA status offers a chance to evaluate the role of the intraperitoneal route in patients selected by biomolecular profiles after primary cytoreduction surgery in advanced ovarian cancer. MATERIALS AND METHODS: We performed a retrospective, multicenter study to assess oncological outcomes depending on adjuvant treatment (intraperitoneal [IP] vs intravenous [IV]) and BRCA status (BRCA1/2 mutated vs. BRCA wild type [WT]). The primary endpoint was to determine progression-free survival. The secondary objectives were overall survival and toxicity. RESULTS: A total of 288 women from eight centers were included: 177 in the IP arm and 111 in the IV arm, grouped into four arms according to BRCA1/2 status. Significantly better PFS was observed in BRCA1/2-mutated patients with IP chemotherapy (HR: 0.35; 95% CI, 0.16-0.75, p = 0.007), which was not present in BRCA1/2-mutated patients with IV chemotherapy (HR: 0.65; 95% CI, 0.37-1.12, p = 0.14). Significantly better OS was also observed in IP chemotherapy (HR: 0.17; 95% CI, 0.06-043, p < 0.0001), but was not present in IV chemotherapy in relation with BRCA mutation (HR: 0.52; 95% CI, 0.22-1.27, p = 0.15). For BRCA WT patients, worse survival was observed regardless of the adjuvant route used. The IP route was more toxic compared to the IV route, but toxicity was equivalent at the long-term follow-up. CONCLUSION: This retrospective study suggests that BRCA status can help to offer an individualized, systematic treatment after optimal primary surgery for advanced ovarian cancer, but is limited by the small sample size. Prospective trials are essential to confirm these results.

Endometrial cancer: predictors and oncological safety of tumor tissue manipulation.

PURPOSE: The main goal of this study is to assess the impact of tumor manipulation on the presence of lympho-vascular space invasion and its influence on oncological results. METHODS: We performed a retrospective multi-centric study amongst patients who had received primary surgical treatment for apparently early-stage endometrial cancer. A multivariate statistical analysis model was designed to assess the impact that tumor manipulation (with the use of uterine manipulator or preoperative hysteroscopy) has on lympho-vascular development (LVSI) in the final surgical specimen. RESULTS: A total of 2852 women from 15 centers were included and divided into two groups based on the lympho-vascular status in the final surgical specimen: 2265 (79.4%) had no LVSI and 587 (20.6%) presented LVSI. The use of uterine manipulator was associated with higher chances of lympho-vascular involvement regardless of the type used: Balloon manipulator (HR: 95% CI 4.64 (2.99-7.33); p < 0.001) and No-Balloon manipulator ([HR]: 95% CI 2.54 (1.66-3.96); p < 0.001). There is no evidence of an association between the use of preoperative hysteroscopy and higher chances of lympho-vascular involvement (HR: 95% CI 0.90 (0.68-1.19); p = 0.479). CONCLUSION: Whilst performing common gynecological procedures, iatrogenic distention and manipulation of the uterine cavity are produced. Our study suggests that the use of uterine manipulator increases the rate of LVSI and, therefore, leads to poorer oncological results. Conversely, preoperative hysteroscopy does not show higher rates of LVSI involvement in the final surgical specimen and can be safely used.

Molecular diagnosis of endometrial cancer from uterine aspirates.

Rapid and reliable diagnosis of endometrial cancer (EC) in uterine aspirates is highly desirable. Current sensitivity and failure rate of histological diagnosis limit the success of this method and subsequent hysteroscopy is often necessary. Using quantitative reverse transcriptase-polymerase chain reaction on RNA from uterine aspirates samples, we measured the expression level of 20 previously identified genes involved in EC pathology, created five algorithms based on combinations of five genes and evaluated their ability to diagnose EC. The algorithms were tested in a prospective, double-blind, multicenter study. We enlisted 514 patients who presented with abnormal uterine bleeding. EC was diagnosed in 60 of the 514 patients (12%). Molecular analysis was performed on the remnants of aspirates and results were compared to the final histological diagnoses obtained through biopsies acquired by aspiration or guided by hysteroscopy, or from the specimens resected by hysterectomy. Algorithm 5 was the best performing molecular diagnostic classifier in the case-control and validation study. The molecular test had a sensitivity of 81%, specificity of 96%, positive predictive value (PPV) of 75% and negative predictive value (NPV) of 97%. A combination of the molecular and histological diagnosis had a sensitivity of 91%, specificity of 97%, PPV of 79% and NPV of 99% and the cases that could be diagnosed on uterine aspirate rose from 76 to 93% when combined with the molecular test. Incorporation of the molecular diagnosis increases the reliability of a negative diagnosis, reduces the need for hysteroscopies and helps to identify additional cases.

Neoadjuvant Chemotherapy plus Interval Cytoreductive Surgery with or without Hyperthermic Intraperitoneal Chemotherapy (NIHIPEC) in the Treatment of Advanced Ovarian Cancer: A Multicentric Propensity Score Study.

INTRODUCTION: Epithelial ovarian cancer (EOC) is primarily confined to the peritoneal cavity. When primary complete surgery is not possible, neoadjuvant chemotherapy (NACT) is provided; however, the peritoneum-plasma barrier hinders the drug effect. The intraperitoneal administration of chemotherapy could eliminate residual microscopic peritoneal tumor cells and increase this effect by hyperthermia. Intraperitoneal hyperthermic chemotherapy (HIPEC) after interval cytoreductive surgery could improve outcomes in terms of disease-free survival (DFS) and overall survival (OS). MATERIALS AND METHODS: A multicenter, retrospective observational study of advanced EOC patients who underwent interval cytoreductive surgery alone (CRSnoH) or interval cytoreductive surgery plus HIPEC (CRSH) was carried out in Spain between 07/2012 and 12/2021. A total of 515 patients were selected. Progression-free survival (PFS) and OS analyses were performed. The series of patients who underwent CRSH or CRSnoH was balanced regarding the risk factors using a statistical analysis technique called propensity score matching. RESULTS: A total of 170 patients were included in each subgroup. The complete surgery rate was similar in both groups (79.4% vs. 84.7%). The median PFS times were 16 and 13 months in the CRSH and CRSnoH groups, respectively (Hazard ratio (HR) 0.74; 95% CI, 0.58-0.94; p = 0.031). The median OS times were 56 and 50 months in the CRSH and CRSnoH groups, respectively (HR, 0.88; 95% CI, 0.64-1.20; p = 0.44). There was no increase in complications in the CRSH group. CONCLUSION: The addition of HIPEC after interval cytoreductive surgery is safe and increases DFS in advanced EOC patients.

Lymphovascular Space Invasion in Early-Stage Endometrial Cancer (LySEC): Patterns of Recurrence and Predictors. A Multicentre Retrospective Cohort Study of the Spain Gynecologic Oncology Group.

The main aim is to compare oncological outcomes and patterns of recurrence of patients with early-stage endometrioid endometrial cancer according to lymphovascular space invasion (LVSI) status. The secondary objective is to determine preoperative predictors of LVSI. We performed a multicenter retrospective cohort study. A total of 3546 women diagnosed with postoperative early-stage (FIGO I-II, 2009) endometrioid endometrial cancer were included. Co-primary endpoints were disease-free survival (DFS), overall survival (OS), and pattern of recurrence. Cox proportional hazard models were used for time-to-event analysis. Univariate and multivariate logistical regression models were employed. Positive LVSI was identified in 528 patients (14.6%) and was an independent prognostic factor for DFS (HR 1.8), OS (HR 2.1) and distant recurrences (HR 2.37). Distant recurrences were more frequent in patients with positive LVSI (78.2% vs. 61.3%, p < 0.01). Deep myometrial invasion (OR 3.04), high-grade tumors (OR 2.54), cervical stroma invasion (OR 2.01), and tumor diameter ≥ 2 cm (OR 2.03) were independent predictors of LVSI. In conclusion, in these patients, LVSI is an independent risk factor for shorter DFS and OS, and distant recurrence, but not for local recurrence. Deep myometrial invasion, cervical stroma invasion, high-grade tumors, and a tumor diameter ≥ 2 cm are independent predictors of LVSI.

Preoperative sampling in endometrial cancer: evaluation of the histopathological agreement with definitive surgical specimen.

PURPOSE: The main goal of this study is to assess the diagnostic agreement between preoperative biopsy and definitive histology of the surgical specimen to determine which sampling method is most suitable for diagnosis of early-stage endometrial cancer. METHODS: We performed a retrospective multicentric study to assess the correlation between three endometrial sampling methods (hysteroscopy, pipelle and D&C) in patients who had undergone preoperative endometrial biopsy and received primary surgical treatment for endometrial cancer. The primary objective was the agreement rate between hysteroscopy (HSC), endometrial biopsy (pipelle) and dilatation and curettage (D&C). RESULTS: A total of 1833 women who underwent preoperative sampling at 15 centers were included: 1042 biopsies were performed by HSC, 703 by pipelle and 88 by D&C. All three methods presented a moderate diagnostic concordance (κ = 0.40-0.61) with the definitive specimen's histology: HSC (κ = 0.47), pipelle sampling (κ = 0.48) and D&C (κ = 0.48). Likewise, a subgroup analysis was performed by histological subtype comparing HSC and endometrial biopsy, showing that neither is superior as a diagnostic method. CONCLUSIONS: According to this study, the use of pipelle sampling could become an adequate diagnostic method in endometrial cancer due to its similar agreement to HSC, ease of use and affordability.

Para-aortic plus pelvic lymphadenectomy in locally advanced cervical cancer: A single institutional experience.

OBJECTIVE: The aim of the study is to assess the safety and efficacy of transperitoneal laparoscopic para-aortic and pelvic lymphadenectomy in the setting of surgical staging of patients with locally advanced cervical cancer (LACC), and to analyse the prognostic value and impact of this staging on the survival prognosis of this condition. STUDY DESIGN: Data from 67 patients with LACC who underwent transperitoneal laparoscopic para-aortic and pelvic lymphadenectomy and who received chemo-radiation therapy were retrospectively analysed. RESULTS: Metastatic lymph nodes (LN) were identified in 32 patients (47.7%), 20 (29.8%) had metastatic LN in the pelvic area and 12 (17.9%) had metastatic LN in the pelvic and para-aortic area. There were no skip metastases in the para-aortic area. After a median follow-up of 54.6 months (5-122.2 months), the 5-year local control and disease-free survival (DFS) rates for the whole group were 91.1% and 60.5% respectively. The five-year DFS for patients without LN metastasis was 86.4%, while for patients with pelvic LN metastases or pelvic and para-aortic metastases was 34.2% and 24.2% respectively (p < 0.001). The five-year overall survival (OS) for the whole group was 67.3%. The mortality rate in patients with para-aortic nodal metastases was increased compared to patients with negative nodes (5-year OS 21.3% vs 81.6% respectively, p = 0.005), but the OS rate was similar in patients with negative nodes and those with only pelvic nodes affected (5-year OS 81.6% vs 70.8% respectively, p = 0.380). This approach allowed the modification of the initial treatment plan in the para-aortic area in 13.4% of patients and in the pelvic area in 28.3%. The overall intraoperative morbidity rate was 5.9%, while the postoperative morbidity rate was 10.4%, with only 3 patients presenting grade 3 morbidity. CONCLUSIONS: Transperitoneal para-aortic and pelvic lymphadenectomy provides precise information about nodal state and allows personalized treatment planning in patients with LACC, avoiding false negative (FN) and false positive (FP) imaging results. In 17.9% of patients, the external beam radiotherapy (EBRT) field had to include the aortic area, whilst 47.7% received pelvic boost to the involved nodes.