Laparoscopic en-bloc pelvic resection for advanced ovarian cancer.

Introduction: Ovarian cancer (OC) exhibits an aggressive behavior, wherein the therapeutic approach always involves both surgery and chemotherapy. Survival outcomes are still related to comprehensive surgical excision of all macroscopic lesions (Rauh-Hain et al., 2017), increasing gynecologic oncologists' efforts to achieve the highest possible complete resection rate (Tozzi et al., 2024). The peritoneum serves as both a dissemination pathway and a barrier that restricts tumor spread beyond its confines. This understanding has prompted the adoption of en-bloc resection strategy for the entire pelvis, involving the removal of pelvic organs along with the surrounding peritoneum. The en-bloc pelvic resection procedure allows for the removal of pelvic disease in all cases of advanced ovarian cancer (Tozzi et al., 2017).Endeavors should be also directed towards minimizing surgical morbidity, by the adoption of minimally invasive surgery for debulking procedures (Tozzi et al., 2023). Case: This video demonstrates a laparoscopic en-bloc pelvic resection with creation of an end-to-end transanal anastomosis. The surgical specimen extraction and the placement of the anvil were performed through the vaginal route.A 75 year-old patient presented with FIGO stage IIIC OC with a 12 cm pelvic mass involving the whole pelvis. The patient was enrolled in the ULTRA-LAP trial and underwent laparoscopic primary debulking surgery with en-bloc pelvic resection. No protective ileostomy was performed and bowel opening occurred on the fifth postoperative day. The patient was discharged on the 11th postoperative day, thereafter completing a regimen of 6 cycles of carboplatin and paclitaxel chemotherapy. Conclusions: The en-bloc resection of the pelvis is a standardized procedure that consists of ten reproducible steps.

An Ultrasound-Based Preoperative Evaluation of the Endometriosis Fertility Index: A Further Step towards Personalized Treatment.

Background: The Endometriosis Fertility Index (EFI), is a crucial validated surgical tool used for predicting fertility outcomes in women with endometriosis. This study aims to assess the concordance between a preoperative clinical and instrumental EFI evaluation (uEFI) and the EFI score obtained during an exploratory laparoscopy prior to surgery (sEFI). Methods: This study presents preliminary data from a broader observational cohort study. The Least Function score for the uEFI was calculated using a modified version of the original surgical EFI by incorporating a clinical examination, advanced ultrasound, and hysterosalpingo-foam sonography (HyFoSy). Results: The preoperative estimation of the EFI (uEFI) demonstrated a high concordance (k = 0.695, ρs = 0.811) with the sEFI. Remarkably, the surgical interventions led to a significant improvement in the EFI values, with 80% of the intermediate EFI transitioning to a high level, thereby highlighting the positive impact of surgery on fertility outcomes. Conclusion: This study highlights the accuracy of preoperative EFI estimation (uEFI) and its strong agreement with intraoperative assessment. It underscores the potential of a preoperative management tool to guide the allocation of infertile women with endometriosis to operative laparoscopy, direct assisted reproductive technology (ART), or spontaneous attempts at pregnancy.

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

OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05862740.

Simple rules, O-RADS, ADNEX and SRR model: Single oncologic center validation of diagnostic predictive models alone and combined (two-step strategy) to estimate the risk of malignancy in adnexal masses and ovarian tumors.

OBJECTIVE: To compare performance of Assessment of Different NEoplasias in the adneXa (ADNEX model), Ovarian-Adnexal Reporting and Data System (O-RADS), Simple Rules Risk (SRR) assessment and the two-step strategy based on the application of Simple Rules (SR) followed by SRR and SR followed by ADNEX in the pre-operative discrimination between benign and malignant adnexal masses (AMs). METHODS: We conducted a retrospective study from January-2018 to December-2021 in which consecutive patients with at AMs were recruited. Accuracy metrics included sensitivity (SE) and specificity (SP) with their 95% confidence intervals (CI) were calculated for ADNEX, O-RADS and SRR. When SR was inconclusive a "two-step strategy" was adopted applying SR + ADNEX model and SR + SRR assessment. RESULTS: A total of 514 women were included, 400 (77.8%) had a benign ovarian tumor and 114 (22.2%) had a malignant tumor. At a threshold malignancy risk of >10%, the SE and SP of ADNEX model, O-RADS and SRR were: 0.92 (95% CI, 0.86-0.96) and 0.88 (95% CI, 0.85-0.91); 0.93 (95% CI, 0.87-0.97) and 0.89 (95% CI, 0.96-0.92); 0.88 (95% CI, 0.80-0.93) and 0.84 (95% CI, 0.80-0.87), respectively. When we applied SR, 109 (21.2%) cases resulted inconclusive. The SE and SP of two-step strategy SR + SRR assessment and SR + ADNEX model were 0.88 (95% CI, 0.80-0.93) and 0.92 (95% CI, 0.89-0.94), SR + ADNEX model 0.90 (95% CI, 0.83-0.95) and 0.93 (95% CI, 0.90-0.96), respectively. CONCLUSIONS: O-RADS presented the highest SE, similar to ADNEX model and SR + ADNEX model. However, the SR + ADNEX model presented the higher performance accuracy with the higher SP and PPV. This two-step strategy, SR and ADNEX model applicated to inconclusive SR, is convenient for clinical evaluation.

Patient Derived Organoids (PDOs), Extracellular Matrix (ECM), Tumor Microenvironment (TME) and Drug Screening: State of the Art and Clinical Implications of Ovarian Cancer Organoids in the Era of Precision Medicine.

Ovarian cancer (OC) has the highest mortality rate of all gynecological malignancies due to the high prevalence of advanced stages of diagnosis and the high rate of recurrence. Furthermore, the heterogeneity of OC tumors contributes to the rapid development of resistance to conventional chemotherapy. In recent years, in order to overcome these problems, targeted therapies have been introduced in various types of tumors, including gynecological cancer. However, the lack of predictive biomarkers showing different clinical benefits limits the effectiveness of these therapies. This requires the development of preclinical models that can replicate the histological and molecular characteristics of OC subtypes. In this scenario, organoids become an important preclinical model for personalized medicine. In fact, patient-derived organoids (PDO) recapture tumor heterogeneity with the possibility of performing drug screening. However, to best reproduce the patient's characteristics, it is necessary to develop a specific extracellular matrix (ECM) and introduce a tumor microenvironment (TME), which both represent an actual object of study to improve drug screening, particularly when used in targeted therapy and immunotherapy to guide therapeutic decisions. In this review, we summarize the current state of the art for the screening of PDOs, ECM, TME, and drugs in the setting of OC, as well as discussing the clinical implications and future perspectives for the research of OC organoids.

Vaginal-Laparoscopic Repair (VLR) of Primary and Persistent Vesico-Vaginal Fistula: Description of a New Technique and Surgical Outcomes.

The main aim of our study was to describe the surgical technique and evaluate the feasibility, efficacy and safety of a vaginal-laparoscopic repair (VLR) of iatrogenic vesico-vaginal fistulae (VVF). Between April-2009 and November-2017, we retrospectively reviewed all clinical, radiological and surgical details of surgery for benign or malignant disease and ended up with VVF. All patients were diagnosed by CT urogram, cystogram and clinical test. The surgical technique was standardised and is described here. Eighteen patients developed VVF after hysterectomy, three after caesarean section and three after hysterectomy and pelvic lymphadenectomy. Twenty-two patients had an average 3 (range 1-5) attempts at fistula repair in other hospitals. In one patient, five attempts were made. The mean size of the fistula was 2.4 cm (range 0.7-3.1 cm). A median 8 weeks (6-16) conservative management with Foley catheter failed in all patients. No conversion to laparotomy and no complication occurred at VLR. Median hospitalisation was 1.4 days (range 1-3). The latter confirmed all patients were dry and tested negative at a repeated filling test. At 36 months follow-up, all patients remained dry. In conclusion, VLR successfully repaired VVF in all patients with primary and persistent VVF. The technique was safe and effective.

Risk-Reducing Salpingo-Oophorectomy (RRSO) Combined with Simultaneous Mastectomy in Women with BRCA 1-2 Mutation Carriers: The Surgical Technique, the Feasibility and Patients' Satisfaction of Multiple Surgeries.

The main goal of our study was to evaluate the surgical technique, the feasibility and patient's satisfaction of multiple surgeries: Risk-reducing salpingo-oophorectomy (RRSO) combined with mastectomy in patients with BRCA 1-2 mutation carriers. We conducted a retrospective analysis of patients with BRCA 1-2 variants who underwent RRSO combined with risk-reducing bilateral mastectomy (RRBM) or surgeries for breast cancer from January-2015 to December-2021. We collected data about surgeries, complications, and patients' satisfaction using a questionnaire submitted 30 days after surgery. We included 54 patients. Forty-eight patients underwent RRSO, and six patients underwent RRSO + Total laparoscopic hysterectomy (LTH). The minor postoperative complications within 30 days were four: one breast seromas aspiration (1.9%), one infectious reconstructive complication treated with antibiotics therapy (1.9%), one Red-Breast-Syndrome (1.9%) and one trocar abdominal hematoma (1.9%) associated with RRSO. The major postoperative complications within 30 days were five: two evacuations of a breast hematoma (3.7%) and three infectious reconstructive complications treated with removal expander/implant (5.6%). No postoperative complications after 30 days were observed. According to the satisfaction questionnaire, more than 90% of patients were satisfied and would have combined surgery again. In conclusion, the multiple surgeries seem feasible and safety with a single anesthesia, a single surgical time, a single postoperative recovery, and a high patients' satisfactions without increasing morbidity.

Uterine Septum with or without Hysteroscopic Metroplasty: Impact on Fertility and Obstetrical Outcomes-A Systematic Review and Meta-Analysis of Observational Research.

Objective: we performed a systematic review/meta-analysis to evaluate the impact of septate uterus and hysteroscopic metroplasty on pregnancy rate-(PR), live birth rate-(LBR), spontaneous abortion-(SA) and preterm labor (PL) in infertile/recurrent miscarriage-(RM) patients. Data sources: a literature search of relevant papers was conducted using electronic bibliographic databases (Medline, Scopus, Embase, Science direct). Study eligibility criteria: we included in this meta-analysis all types of observational studies that evaluated the clinical impact of the uterine septum and its resection (hysteroscopic metroplasty) on reproductive and obstetrics outcomes. The population included were patients with a diagnosis of infertility or recurrent pregnancy loss. Study appraisal and synthesis methods: outcomes were evaluated according to three subgroups: (i) Women with untreated uterine septum versus women without septum (controls); (ii) Women with treated uterine septum versus women with untreated septum (controls); (iii) Women before and after septum removal. Odds ratios (OR) with 95% confidence intervals (CI) were calculated for the outcome measures. A p-value < 0.05 was considered statistically significant. Subgroup analysis was performed according to the depth of the septum. Sources of heterogeneity were explored by meta-regression analysis according to specific features: assisted reproductive technology/spontaneous conception, study design and quality of papers included Results: data from 38 studies were extracted. (i) septum versus no septum: a lower PR and LBR were associated with septate uterus vs. controls (OR 0.45, 95% CI 0.27−0.76; p < 0.0001; and OR 0.21, 95% CI 0.12−0.39; p < 0.0001); a higher proportion of SA and PL was associated with septate uterus vs. controls (OR 4.29, 95% CI 2.90−6.36; p < 0.0001; OR 2.56, 95% CI 1.52−4.31; p = 0.0004). (ii) treated versus untreated septum: PR and PL were not different in removed vs. unremoved septum(OR 1.10, 95% CI 0.49−2.49; p = 0.82 and OR 0.81, 95% CI 0.35−1.86; p = 0.62); a lower proportion of SA was associated with removed vs. unremoved septum (OR 0.47, 95% CI 0.21−1.04; p = 0.001); (iii) before-after septum removal: the proportion of LBR was higher after the removal of septum (OR 49.58, 95% CI 29.93−82.13; p < 0.0001) and the proportion of SA and PL was lower after the removal of the septum (OR 0.02, 95% CI 0.02−0.04; p < 0.000 and OR 0.05, 95% CI 0.03−0.08; p < 0.0001) Conclusions: the results show the detrimental effect of the uterine septum on PR, LBR, SA and PL. Its treatment reduces the rate of SA.

New Light on Endometrial Thickness as a Risk Factor of Cancer: What Do Clinicians Need to Know?

Transvaginal ultrasound (TVUS) represents an accurate and noninvasive technique to investigate endometrial thickness (ET) in the early diagnosis of endometrial cancer (EC). In the literature, for maximum ET there is no consensus on the cutoff value for normal ET in postmenopause for either symptomatic or asymptomatic women. Most patients with EC present with postmenopausal bleeding (PMB) and in these patients is necessary to perform TVUS to evaluate ET as an indicator for endometrial biopsy. On the contrary, if ET is incidentally detected in postmenopausal patients without bleeding, endometrial sampling for a postmenopausal woman without bleeding should not be routinely performed, although it is estimated that up to 15% of EC occurs in women without vaginal bleeding. The aim of our review was to give clinicians necessary and useful knowledge on the role of TVUS and ET for early detection of EC in their daily routine practice. Based on the most important studies in the literature, we summarized that in premenopausal woman with abnormal uterine bleeding, an optimal cutoff for ET has not yet been established. For postmenopausal women with PMB, at low risk, and ET <4 mm, a follow-up scan could be offered, and for women with ET ≥4 mm, office hysteroscopy-guided endometrial sampling is recommended independently of ET results. On the other hand, in postmenopausal women with PMB and at high risk of EC, office hysteroscopy-guided endometrial sampling is necessary. In postmenopausal women without PMB and ET ≥4 mm, arbitrary endometrial sampling is not recommended, but evaluated case by case based on risk factors. In conclusion, there is broad consensus on the importance of TVUS and the need for further investigation based on risk factors of EC.

MUM-1 immunohistochemistry has high accuracy and reliability in the diagnosis of chronic endometritis: a multi-centre comparative study with CD-138 immunostaining.

PURPOSE: The current gold standard for chronic endometritis (CE) diagnosis is immunohistochemistry (IHC) for CD-138. However, IHC for CD-138 is not exempt from diagnostic limitations. The aim of our study was to evaluate the reliability and accuracy of MUM-1 IHC, as compared with CD-138. METHODS: This is a multi-centre, retrospective, observational study, which included three tertiary hysteroscopic centres in university teaching hospitals. One hundred ninety-three consecutive women of reproductive age were referred to our hysteroscopy services due to infertility, recurrent miscarriage, abnormal uterine bleeding, endometrial polyps or myomas. All women underwent hysteroscopy plus endometrial biopsy. Endometrial samples were analysed through histology, CD138 and MUM-1 IHC. The primary outcome was to evaluate the diagnostic accuracy of MUM-1 IHC for CE, as compared with CD-138 IHC. RESULTS: Sensitivity and specificity of CD-138 and MUM-1 IHC were respectively 89.13%, 79.59% versus 93.48% and 85.03%. The overall diagnostic accuracy of MUM-1 and CD-138 IHC were similar (AUC = 0.893 vs AUC = 0.844). The intercorrelation coefficient for single measurements was high between the two techniques (ICC = 0.831, 0.761-0.881 95%CI). However, among CE positive women, MUM-1 allowed the identification of higher number of plasma cells/hpf than CD-138 (6.50 [SD 4.80] vs 5.05 [SD 3.37]; p = 0.017). Additionally, MUM-1 showed a higher inter-observer agreement as compared to CD-138. CONCLUSION: IHC for MUM-1 and CD-138 showed a similar accuracy for detecting endometrial stromal plasma cells. Notably, MUM-1 showed higher reliability in the paired comparison of the individual samples than CD-138. Thus, MUM-1 may represent a novel, promising add-on technique for the diagnosis of CE.

Role of Renin-Angiotensin-Aldosterone System and Cortisol in Endometriosis: A Preliminary Report.

Endometriosis is a chronic inflammatory disease associated with pelvic pain, infertility, and increased cardiovascular risk. Recent studies suggest a possible role of aldosterone as a pro-inflammatory hormone in the pathogenesis of the disease. Cortisol is also an important mediator of stress reaction, but its role is controversial in endometriosis. The aim of this study was to evaluate aldosterone and cortisol levels and blood pressure values in women with endometriosis. We measured blood pressure, plasma aldosterone, renin, cortisol, and dehydroepiandrosterone sulfate (DHEAS) in 20 women with untreated minimal or mild pelvic endometriosis compared with 20 healthy controls matched for age and body mass index. Aldosterone values were similar in the two groups, while renin was significantly lower and the aldosterone to renin ratio was significantly higher in patients with endometriosis than in controls. Systolic blood pressure was in the normal range, but significantly higher in patients with endometriosis. Morning plasma cortisol was normal, but significantly lower in patients with endometriosis compared with controls, while DHEAS to cortisol ratio was similar in the two groups. These preliminary results are evidence of increased biological aldosterone activity and dysregulation of the hypothalamic-pituitary-adrenal axis in early stages of endometriosis. These alterations could play a role in disease development, suggesting new therapeutic targets for aldosterone receptor blockers.

Efficacy of risk-reducing salpingo-oophorectomy in BRCA1-2 variants and clinical outcomes of follow-up in patients with isolated serous tubal intraepithelial carcinoma (STIC).

OBJECTIVE: Serous tubal intraepithelial carcinoma (STIC) is currently considered the precursor lesion of pelvic high-grade serous carcinoma. The management of STIC diagnosed after risk-reducing salpingo-oophorectomy (RRSO) in women with BRCA1-2 variants remains unclear. The aim of our study was to evaluate the incidence of STIC, serous tubal intraepithelial lesions (STIL) and occult invasive cancer (OC) and to determine the long-term outcomes of these patients. METHODS: We conducted a retrospective study of patients with BRCA 1-2 variants who underwent RRSO between January-2010 and Dicember-2020 at the Clinic of Gynaecology of University of Padova. INCLUSION CRITERIA: women with a negative pelvic examination at the last screening prior to RRSO, patients with fallopian tubes analysed using the SEE-FIM protocol. EXCLUSION CRITERIA: patients with a positive gynaecologic screening or with ovarian/tubal cancer prior to RRSO. RESULTS: We included 153 patients. STICs were diagnosed in 4 patients (2.6%) and STILs in 6 patients (3.9%). None of the patients with STIC underwent restaging surgery or adjuvant chemotherapy; all patients were followed closely every 6 months. None of the patients developed primary peritoneal carcinomas (PPCs) with a median FUP of 54.5 months (15-106). OC was diagnosed in 3 patients (2%). All patients with OC underwent staging surgery, and one patient developed a peritoneal carcinoma (PC) after 18 months by staging surgery. CONCLUSION(S): The incidence of STIC, STIL and OC after RRSO in BRCA1-2 variants was low. Our results demonstrated that long-term close surveillance in patients diagnosed with STIC should be considered a possible management strategy.

Endometrial Cancer Risk Prediction According to Indication of Diagnostic Hysteroscopy in Post-Menopausal Women.

We conducted a prospective observational study investigating the clinical relevance of endometrial thickness (ET) and abnormal uterine bleeding (AUB) on endometrial cancer (EC) risk in a cohort of postmenopausal patients undergoing diagnostic hysteroscopy and endometrial biopsy. Patients were divided into two groups according to the indication of diagnostic hysteroscopy: ET_Group (asymptomatic patients with endometrial thickness ≥ 4 mm) and AUB_Group (patients with a history of abnormal uterine bleeding). We further divided the AUB_Group into two subgroups based on endometrial thickness (AUB_Subgroup1: ET < 4 mm; AUB_Subgroup2: ET ≥ 4 mm). The primary outcome was the risk of endometrial cancer and atypical hyperplasia according to the indications of diagnostic hysteroscopy (AUB, ET ≥ 4 mm or both). The secondary outcome was to determine the best cut-off value of endometrial thickness to predict endometrial cancer in asymptomatic postmenopausal women. The prevalence of endometrial cancer and atypical hyperplasia in AUB_Group and ET_Group was 21% and 6.7% respectively. As well as for EC alone, higher prevalence of both conditions was observed in AUB_Subgroup2 (29.3%) in comparison to AUB_Subgroup1 (10.6%; p < 0.001). In asymptomatic patients the cut-off of endometrial thickness that showed the best sensitivity and specificity to diagnose endometrial cancer (100% and 80% respectively) was 11 mm (AUC of 91.4%; Expß: 1067; CI 95%). In conclusion, considering the high risk of neoplasia, diagnostic hysteroscopy with endometrial biopsy should be mandatory in cases of abnormal uterine bleeding in postmenopausal patients. Moreover, we want to emphasize the need for further evidence stating the clinical relevance of endometrial thickness value in asymptomatic patients and the impact of individual risk factors on endometrial cancer development.

Mutational and Immunophenotypic Profiling of a Series of 8 Tubo-ovarian Carcinosarcomas Revealed a Monoclonal Origin of the Disease.

Carcinosarcomas are rare, highly aggressive neoplasms composed of a combination of carcinomatous and sarcomatous elements. These tumors represent a paradigmatic field for the study of intratumor heterogeneity. A series of 8 tubo-ovarian carcinosarcomas was characterized for the following: (i) immunohistochemical expression of MNF116, epithelial membrane antigen, vimentin, S100, chromogranin, synaptophysin, desmin, myogenin (MYF4), and p53; (ii) mutational profiling of KRAS, BRAF, PIK3CA, NRAS, TP53, and DICER1 genes. Heterologous differentiation was present in 6 of 8 tumors. Cytokeratin MNF116 and epithelial membrane antigen were positive in all the carcinomatous components and in 87.5% and 50.0% of the sarcomatous components, respectively. The sarcomatous components showed positive staining for vimentin in all cases. Two cases demonstrated positivity for neuroendocrine markers in their carcinomatous components. All rhabdomyosarcomas were positive for desmin and MYF-4. Chondrosarcomas were positive for S100. All but one tumor showed similar p53 immunoreactivity in both the carcinomatous and sarcomatous components, and one case showed cytoplasmic p53 expression. Three of 8 cases (37.5%) showed TP53 mutations, and, in 2 cases, the TP53 mutation was shared by both epithelial and mesenchymal components. DICER1 mutation was found in all components of one case. Mutations in KRAS, NRAS, BRAF, and PIK3CA genes were not found in the study cohort. Our results highlight the heterogeneity of ovarian carcinosarcomas at the phenotypic level. A common mutational signature was observed in both components in 3 of 4 informative tumors. More studies are required to dissect different levels of ovarian carcinosarcomas' heterogeneity in order to define the best therapeutic approaches to these aggressive neoplasms.

Imaging Modalities for Diagnosis of Deep Pelvic Endometriosis: Comparison between Trans-Vaginal Sonography, Rectal Endoscopy Sonography and Magnetic Resonance Imaging. A Head-to-Head Meta-Analysis.

OBJECTIVES: A meta-analysis, with a head-to-head approach, was carried out to compare the three most common techniques for a deep pelvic endometriosis (DPE) diagnosis. We focused on: transvaginal-sonography (TVS), magnetic-resonance imaging (MRI), and rectal-endoscopy-sonography (RES). METHODS: Electronic databases were searched from their inception until December 2018. All prospective and well-defined retrospective studies carried out in tertiary referral centers were considered. This review was reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Synthesizing Evidence from Diagnostic Accuracy Tests (SEDATE) guidelines. We considered only papers in which at least two imaging modalities were compared in the same set of patients (head-to-head approach). Meta-analysis of diagnostic test accuracy (DTA) was performed separately for each location of interest. Bivariate or univariate approach has been applied when appropriate. We analyze the DTA of TVS vs. MRI, TVS vs. RES, and MRI vs. RES. RESULTS: Our meta-analysis (17 studies included) showed high-to-moderate DTA of TVS for all endometriosis locations (apart from recto-vaginal septum (RVS)) that were not statistically different from MRI and RES for those localized in the posterior compartment. RES results were more accurate than MRI for RS lesions but less accurate than TVS for other pelvic locations, except for RVS. CONCLUSIONS: All approaches provide good accuracy with specific strong points. Ultrasonography demonstrated a diagnostic accuracy not inferior to MRI and RES; therefore, it must be considered the primary approach for DPE diagnosis. MRI has to be considered as a valuable approach in settings where highly skilled sonographers are not available. Keypoints: (1) We confirmed the non-inferiority of TVS compared to MRI and RES for the diagnosis of specific pelvic anatomic location of endometriosis lesions. (2) Ultrasonography could be considered the primary approach for DPE diagnosis (less invasive than RES and less expensive than MRI). (3) MRI has to be considered as a valuable approach in settings where skilled sonographers are not available.

Patterns of Fertility Preservation and Pregnancy Outcome After Breast Cancer at a Large Comprehensive Cancer Center.

BACKGROUND: In the last decades, long-term outcomes of breast cancer (BC) patients have improved, raising new survivorship issues, including fertility preservation and safety of pregnancy after BC. This study assesses evolution in patterns of fertility discussion/preservation over time and reports pregnancy outcomes in a cohort of young BC patients. METHODS: A retrospective cohort of 590 BC patients aged ≤40 diagnosed between 2000 and 2016 at a large cancer center was identified. Fertility counseling and preservation patterns for patients receiving chemotherapy were analyzed and compared for two cohorts: 2004-2006 and 2014-2016 (total n = 161). Outcomes were reported for patients with documented pregnancy after BC. RESULTS: Significantly, more patients diagnosed in 2014-2016 had evidence of discussion on fertility issues and/or application of fertility preservation techniques versus patients diagnosed in 2004-2006 (82.9% vs. 66.0%, p = 0.017). In particular, there was a significant difference in rate of documented fertility issues discussion (67.6% vs. 34.0%, p < 0.001). Age >35 and parity were associated with lower rates of fertility discussion/preservation. However, rates significantly improved over time (77.6% in 2014-2016 vs. 58.1% in 2004-2006 for patients aged >35, p = 0.046; 80.7% in 2014-2016 vs. 57.6% in 2004-2006 for patients with children at diagnosis, p = 0.018). Twenty-six patients with pregnancy after BC were identified; eight delivered at the age of >40. No complications for women or newborns were reported. Only two patients experienced BC relapse. CONCLUSIONS: In this small retrospective cohort, no safety concerns were identified for pregnancy after BC. The importance attributed by clinicians to address fertility issues has increased over time.

Primary debulking surgery versus primary neoadjuvant chemotherapy for high grade advanced stage ovarian cancer: comparison of survivals.

Background The aim of the study was to analyze the overall survival (OS) and progression free survival (PFS) of patients with high grade and advanced stage epithelial ovarian cancer (EOC) with at least 60 months of follow-up treated in a single gynecologic oncology institute. We compared primary debulking surgery (PDS) versus neoadjuvant chemotherapy plus interval debulking surgery (NACT + IDS) stratifying data based on residual disease with the intent to identify the rationale for therapeutic option decision and the role of laparoscopic evaluation of resectability for that intention. Patients and methods This is observational retrospective study on consecutive patients with diagnosis of high grade and International Federation of Gynecology and Obstetrics (FIGO) stage III/IV EOC referred to our center between January 2008 and May 2012. We selected only patients with a follow-up of at least 60 months. Primary endpoint was to compare PDS versus NACT + IDS in term of progression free survival (PFS) and overall survival (OS). Secondary endpoints were PFS and OS stratifying data according to residual disease after surgery in patients receiving PDS versus NACT + IDS. Finally, through Cox hazards models, we tested the prognostic value of different variables (patient age at diagnosis, residual disease after debulking, American Society of Anesthesiologists (ASA) stage, number of adjuvant-chemotherapy cycles) for predicting OS. Results A total number of 157 patients were included in data analysis. Comparing PDS arm (108 patients) and NACT + IDS arm (49 patients) we found no significant differences in term of OS (41.3 versus 34.5 months, respectively) and PFS (17.3 versus 18.3 months, respectively). According to residual disease we found no significant differences in term of OS between NACT + IDS patients with residual disease = 0 and PDS patients with residual disease = 0 or residual disease = 1, as well as no significant differences in PFS were found comparing NACT + IDS patients with residual disease = 0 and PDS patients with residual disease = 0; contrarily, median PFS resulted significantly lower in PDS patients receiving optimal debulking (residual disease = 1) in comparison to NACT + IDS patients receiving complete debulking (residual disease = 0). PDS arm was affected by a significant higher rate of severe post-operative complications (grade 3 and 4). Diagnostic laparoscopy before surgery was significantly associated with complete debulking. Conclusions We confirm previous findings concerning the non-superiority of NACT + IDS compared to PDS for the treatment of EOC, even if NACT + IDS treatment was associated with significant lower rate of post-operative complications. On the other hand, selecting patients for NACT + IDS, based on laparoscopic evaluation of resectabilty prolongs the PFS and does not worse the OS compared to the patients not completely debulked with PDS.

Effects of chronic endometritis therapy on in vitro fertilization outcome in women with repeated implantation failure: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the impact of antibiotic therapy for chronic endometritis (CE) on IVF outcome. DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Infertile women with history of recurrent implantation failure, defined as two or more failed ETs, undergoing one or more IVF cycle(s). INTERVENTION(S): The review was registered in PROSPERO (CRD42017062494) before the start of the literature search. Observational studies were identified by searching electronic databases. The following comparators were included: women with CE receiving antibiotics vs. untreated controls; women with cured CE vs. women with persistent CE; and women with cured CE vs. women with normal endometrial histology (negative for CE). The summary measures were reported as odds ratio (OR) with 95% confidence interval (CI). MAIN OUTCOME MEASURE(S): Clinical pregnancy rate (CPR), ongoing pregnancy rate/live birth rate (OPR/LBR), implantation rate (IR), miscarriage rate. RESULT(S): A total of 796 patients (from five studies) were included. Women receiving antibiotic therapy (without the histologic confirmation of CE cure) did not show any advantage in comparison with untreated controls (OPR/LBR, CPR, and IR). Patients with cured CE showed higher OPR/LBR (OR 6.81), CPR (OR 4.02), and IR (OR 3.24) in comparison with patients with persistent CE. In vitro fertilization outcome was comparable between women with cured CE and those without CE (OPR/LBR, CPR, and IR). Miscarriage rate was not significantly different between groups. CONCLUSION(S): Chronic endometritis therapy may improve IVF outcome in patients suffering from recurrent implantation failure. A control biopsy should always confirm CE resolution before proceeding with IVF.

Endometrial scratch injury before intrauterine insemination: is it time to re-evaluate its value? Evidence from a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To assess the impact of endometrial scratch injury (ESI) on the outcomes of intrauterine insemination (IUI) stimulated cycles. DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Infertile women undergoing one or more IUI stimulated cycles. INTERVENTION(S): Randomized controlled trials (RCTs) were identified by searching electronic databases. We included RCTs comparing ESI (i.e., intervention group) during the course of IUI stimulated cycle (C-ESI) or during the menstrual cycle preceding IUI treatment (P-ESI) with controls (no endometrial scratch). The summary measures were reported as odds ratio (OR) with 95% confidence-interval (CI). MAIN OUTCOME MEASURE(S): Clinical pregnancy rate, ongoing pregnancy rate, multiple pregnancy rate, ectopic pregnancy rate, miscarriage rate. RESULT(S): Eight trials were included in the meta-analysis, comprising a total of 1,871 IUI cycles. Endometrial scratch injury was associated with a higher clinical pregnancy rate (OR 2.27) and ongoing pregnancy rate (OR 2.04) in comparison with the controls. No higher risk of multiple pregnancy (OR 1.09), miscarriage (OR 0.80), or ectopic pregnancy (OR 0.82) was observed in patients receiving ESI. Subgroup analysis based on ESI timing showed higher clinical pregnancy rate (OR 2.57) and ongoing pregnancy rate (OR 2.27) in patients receiving C-ESI and no advantage in patients receiving P-ESI. CONCLUSION(S): Available data suggest that ESI performed once, preferably during the follicular phase of the same cycle of IUI with flexible aspiration catheters, may improve clinical pregnancy and ongoing pregnancy rates in IUI cycles. Endometrial scratch injury does not appear to increase the risk of multiple pregnancy, miscarriage, or ectopic pregnancy.