Intraoperative Ketorolac and Outcomes after Ovarian Cancer Surgery.

INTRODUCTION: Surgery is the cornerstone of ovarian cancer treatment. However, surgery and perioperative inflammation have been described as potentially pro-metastagenic. In various animal models and other human cancers, intraoperative administration of non-steroidal anti-inflammatory drugs (NSAIDs) appears to have a positive impact on patient outcomes. MATERIALS AND METHODS: In this unicentric retrospective study, we provide an exploratory analysis of the safety and potential benefit of intraoperative administration of ketorolac on the outcome of patients undergoing surgery for ovarian cancer. The study population included all patients who were given a diagnosis of ovarian, fallopian tube or peritoneal cancer by the multidisciplinary oncology committee (MOC) of the Cliniques universitaires Saint-Luc between 2015 and 2020. RESULTS: We included 166 patients in our analyses, with a median follow-up of 21.8 months. Both progression-free survival and overall survival were superior in patients who received an intraoperative injection of ketorolac (34.4 months of progression-free survival in the ketorolac group versus 21.5 months in the non-ketorolac group (p = 0.002), and median overall survival was not reached in either group but there was significantly higher survival in the ketorolac group (p = 0.004)). We also performed subgroup analyses to minimise bias due to imbalance between groups on factors that could influence patient survival, and the group of patients receiving ketorolac systematically showed a better outcome. Uni- and multivariate analyses confirmed that administration of ketorolac intraoperatively was associated with better progression-free survival (HR = 0.47 on univariate analysis and 0.43 on multivariate analysis, p = 0.003 and 0.023, respectively). In terms of complications, there were no differences between the two groups, either intraoperatively or postoperatively. CONCLUSION: Our study has shown a favourable association between the use of ketorolac during surgery and the postoperative progression of ovarian cancer in a group of 166 patients, without any rise in intra- or postoperative complications. These encouraging results point to the need for a prospective study to confirm the benefit of intraoperative administration of ketorolac in ovarian cancer surgery.

Quality of surgery and treatment and its association with hospital volume: A population-based study in more than 5000 Belgian ovarian cancer patients.

BACKGROUND: Different sets of quality indicators are used to identify areas for improvement in ovarian cancer care. This study reports transparently on how (surgical) indicators were measured and on the association between hospital volume and indicator results in Belgium, a country setting without any centralisation of ovarian cancer care. METHODS: From the population-based Belgian Cancer Registry, patients with a borderline malignant or invasive epithelial ovarian tumour diagnosed between 2014 and 2018 were selected and linked to health insurance and vital status data (n = 5119). Thirteen quality indicators on diagnosis and treatment were assessed and the association with hospital volume was analysed using logistic regression adjusted for case-mix. RESULTS: The national results for most quality indicators on diagnosis and systemic therapy were around the predefined target value. Other indicators showed results below the benchmark: genetic testing, completeness of staging surgery, lymphadenectomy with at least 20 pelvic/para-aortic lymph nodes removed, and timely start of chemotherapy after surgery (within 42 days). Ovarian cancer care in Belgium is dispersed over 100 hospitals. Lower volume hospitals showed poorer indicator results compared to higher volume hospitals for lymphadenectomy, staging, timely start of chemotherapy and genetic testing. In addition, surgery for advanced stage tumours was performed less often in lower volume hospitals. CONCLUSIONS: The indicators that showed poorer results on a national level were also those with poorer results in lower-volume hospitals compared to higher-volume hospitals, consequently supporting centralisation. International benchmarking is hampered by different (surgical) definitions between countries and studies.

Immunosuppressive low-density neutrophils in the blood of cancer patients display a mature phenotype.

The presence of human neutrophils in the tumor microenvironment is strongly correlated to poor overall survival. Most previous studies have focused on the immunosuppressive capacities of low-density neutrophils (LDN), also referred to as granulocytic myeloid-derived suppressor cells, which are elevated in number in the blood of many cancer patients. We observed two types of LDN in the blood of lung cancer and ovarian carcinoma patients: CD45high LDN, which suppressed T-cell proliferation and displayed mature morphology, and CD45low LDN, which were immature and non-suppressive. We simultaneously evaluated the classical normal-density neutrophils (NDN) and, when available, tumor-associated neutrophils. We observed that NDN from cancer patients suppressed T-cell proliferation, and NDN from healthy donors did not, despite few transcriptomic differences. Hence, the immunosuppression mediated by neutrophils in the blood of cancer patients is not dependent on the cells' density but rather on their maturity.

Association between hospital volume and outcomes in invasive ovarian cancer in Belgium: A population-based study.

OBJECTIVES: To study the association between hospital volume and outcomes in patients with invasive epithelial ovarian cancer (EOC). METHODS: This study included 3988 patients diagnosed with invasive EOC between 2014 and 2018, selected from the population-based database of the Belgian Cancer Registry (BCR), and coupled with health insurance and vital status data. The associations between hospital volume and observed survival since diagnosis were assessed with Cox proportional hazard models, while volume associations with 30-day post-operative mortality and complicated recovery were evaluated using logistic regression models. RESULTS: Treatment for EOC was very dispersed with half of the 100 centres treating fewer than six patients per year. The median survival of patients treated in centres with the highest-volume quartile was 2.5 years longer than in those with the lowest-volume quartile (4.2 years versus 1.7 years). When taking the case-mix of hospitals into account, patients treated in the lowest volume centres had a 47% higher hazard to die than patients treated in the highest volume centres (HR: 1.47, 95% CI: 1.11-1.93, p = 0.006) over the first five years after incidence. A similar association was found when focussing on the surgical volume of the hospitals and considering only operated patients with invasive EOC. Lastly, the 30-day post-operative mortality decreased significantly with increasing surgical volume. CONCLUSIONS: The large dispersion of care and expertise within Belgium and the volume-outcome associations observed in this study support the implementation of the concentration of care for patients with invasive EOC in reference centres.

Centralizing surgery for ovarian cancer in a 'non-centralizing' country (Belgium): the UNGO (UCLouvain Network of Gynaecological Oncology) experience.

OBJECTIVE: In Belgium there is no centralization of surgery for ovarian cancer, with more than 100 centers treating around 800 cases per year. In 2017 a network with several collaborating hospitals was established to centralize surgery for ovarian cancer (UCLouvain Network of Gynecological Oncology; UNGO) following publication of the European Society of Gynecological Oncology (ESGO) recommendations and quality criteria for surgery of advanced ovarian cancer. We obtained ESGO accreditation in 2019. METHODS: We retrospectively collected data associated with patients undergoing surgery in our institution from 2007 to 2016, before the creation of the network (cohort 1) and, following the establishment of UNGO (2017-2021), patients undergoing surgery were prospectively registered in a REDCap database (cohort 2). The outcomes of the two cohorts were compared. RESULTS: A total of 314 patients underwent surgery in our institution from 2007 and 2021: 7.5 patients/year in cohort 1 (retrospective, 2007-2016) and 40.8 patients/year in cohort 2 (after network creation, 2017-2021). Median disease-free survival was increased from 16.5 months (range 13.2-20.4) in cohort 1 to 27.1 months (range 21.5-33.2) in cohort 2 (p=0.0004). In cohort 2, the rate of patients with residual disease at the end of the surgery was significantly less (18.7% vs 8.8%, p=0.023), although more patients in cohort 1 received neoadjuvant chemotherapy (89% vs 54%, p<0.001). However, there was a higher rate of complications in the patients in cohort 2 (18.8% vs 30%, p=0.041). CONCLUSION: Our study shows that, with the help of ESGO and its recommendations, we have been able to create an efficient advanced ovarian cancer centralized network and this may provide an improvement in the quality of care.

Hysteroscopic management of molar pregnancy: A series of 36 cases.

Background: Hydatidiform Mole (HM) is the most common form of gestational trophoblastic disease. Dilatation and curettage is the classical treatment of this affection. Hysteroscopic resection (HsR) is an alternative for the treatment of intra-uterine pathology. Objective: To describe the feasibility of HsR for the management of HM. Result: Case series of patients who had a complete or partial HM confirmed by histological examination of the trophoblastic tissue resected by operative hysteroscopy between 2007 and 2019. After approval of our ethics committee, we evaluated 36 patients who underwent hysteroscopic resection for molar pregnancy. Histological analysis showed partial HM in 28 patients (77.8%) and complete HM in 8 (22.2%). Main surgical complications were uterine perforation in one patient and glycine resorption in 10 patients with two cases of hyponatremia corrected by standard treatment. We performed an ultrasound control 1 month after the intervention in 19 patients (52.8%) as they had slow decrease of HCG or bleeding complaints and found retained product of conception (RPOC) in six patients (16.7%). Conclusion: This first report on a small number of patients demonstrate that hysteroscopic resection is a feasible procedure for the management of molar pregnancy. Direct visualization of the procedure helps the surgeon to control the resection. Further studies are mandatory to compare this technique with D&C in term of RPOC and fertility outcomes as it remains the standard treatment.

PARa-aOrtic LymphAdenectomy in locally advanced cervical cancer (PAROLA trial): a GINECO, ENGOT, and GCIG study.

BACKGROUND: Positron emission tomography/computed tomography (PET/CT) fails to detect approximately 25% of aortic lymph node metastasis in patients with PET/CT stage IIIC1 cervical cancer. Surgical staging could lead to treatment modification and to improved para-aortic and distant control. PRIMARY OBJECTIVES: To demonstrate if chemoradiation with tailored external beam radiation field based on surgical staging and pathologic examination of the para-aortic lymph node is associated with improved 3-year disease-free survival compared with patients staged with PET/CT staging only. STUDY HYPOTHESIS: Surgical staging followed by tailored chemoradiation will improve disease-free survival while avoiding unnecessary prophylactic extended-field chemoradiation in patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIIC1 cervical cancer. TRIAL DESIGN: This is an international multicenter, randomized, phase III study. Eligible patients will be randomized 1:1 between PET/CT staging followed by chemoradiation (control arm), or surgical staging followed by tailored chemo-radiation (experimental arm). Randomization will be stratified by tumor stage according to TNM classification, center, and adjuvant treatment. MAJOR INCLUSION/EXCLUSION CRITERIA: Main inclusion criteria are histologically proven PET/CT FIGO stage IIIC1 cervical cancer. Main exclusion criteria include unequivocal positive common iliac or para-aortic lymph node at pre-therapeutic imaging PET/CT. PRIMARY ENDPOINTS: The primary endpoint is disease-free survival defined as the time from randomization until first relapse (local, regional, or distant), or death from any cause. SAMPLE SIZE: 510 eligible patients ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: The estimated date for completing accrual will be Q2 2027. The estimated date for presenting results will be Q4 2030. TRIAL REGISTRATION NUMBER: NCT05581121.

Outcomes after Laparoscopic Excision of Bladder Endometriosis Using a CO2 Laser: A Review of 207 Cases in a Single Center.

STUDY OBJECTIVE: Assess efficacy, safety, fertility outcomes and recurrence after laparoscopic resection of bladder endometriosis (BE) using a CO2 laser. DESIGN: Retrospective cohort study. SETTINGS: University gynecologic surgery unit, referral center for endometriosis. PATIENTS: A total of 207 women having undergone laparoscopic BE excision between January 1998 and January 2019. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Intra- and postoperative complication rates. Disease recurrence and fertility outcomes in patients with a minimum 1-year follow-up (n = 176) for "isolated" and "non-isolated" BE groups. RESULTS: Forty-three patients presented with isolated BE. Bladder "shaving" without mucosae opening was performed in 50.7% cases. No intraoperative complications were noted. One postoperative grade 3 complication was related to BE excision: a bladder breach requiring closure by repeat laparoscopy. Mean (± SD) follow-up was 7.05 (± 4.65) years. In patients wishing to conceive (n = 132), the total pregnancy rate (PR) was 75% (48.5% spontaneous), 76.19% in the isolated BE group (56.3% spontaneous). Among the 94 patients with previous infertility, 74.5% conceived, 50% spontaneously. No statistical difference was found in PR and need for in vitro fertilization between isolated and nonisolated BE groups. BE recurrence rate was 3.4%. No difference was observed between groups with full-thickness bladder resection (4/88) and shaving (2/88) (p = .406). Age at surgery (hazard ratio 0.91 [0.84-0.98], p = .016) and postoperative pregnancy (hazard ratio 0.07 [0.01-0.91], p = .042) showed influence on disease recurrence. CONCLUSIONS: The study demonstrates that laparoscopic BE removal is feasible with very low complications rates and was associated with high PR (both spontaneous and in vitro fertilization), even in patients with previous infertility. BE recurrence is lower than for other endometriosis locations. Bladder endometriosis; Laparoscopy; Deep infiltrating endometriosis; Fertility; Partial bladder resection.

HELIOS-expressing human CD8 T cells exhibit limited effector functions.

Introduction: The transcription factor HELIOS is primarily known for its expression in CD4 regulatory T cells, both in humans and mice. In mice, HELIOS is found in exhausted CD8 T cells. However, information on human HELIOS+ CD8 T cells is limited and conflicting. Methods: In this study, we characterized by flow cytometry and transcriptomic analyses human HELIOS+ CD8 T cells. Results: These T cells primarily consist of memory cells and constitute approximately 21% of blood CD8 T cells. In comparison with memory HELIOS- T-BEThigh CD8 T cells that displayed robust effector functions, the memory HELIOS+ T-BEThigh CD8 T cells produce lower amounts of IFN-γ and TNF-α and have a lower cytotoxic potential. We wondered if these cells participate in the immune response against viral antigens, but did not find HELIOS+ cells among CD8 T cells recognizing CMV peptides presented by HLA-A2 and HLA-B7. However, we found HELIOS+ CD8 T cells that recognize a CMV peptide presented by MHC class Ib molecule HLA-E. Additionally, a portion of HELIOS+ CD8 T cells is characterized by the expression of CD161, often used as a surface marker for identifying TC17 cells. These CD8 T cells express TH17/TC17-related genes encoding RORgt, RORa, PLZF, and CCL20. Discussion: Our findings emphasize that HELIOS is expressed across various CD8 T cell populations, highlighting its significance beyond its role as a transcription factor for Treg or exhausted murine CD8 T cells. The significance of the connection between HELIOS and HLA-E restriction is yet to be understood.

Development of SARS-CoV2 humoral response including neutralizing antibodies is not sufficient to protect patients against fatal infection.

More than a year after the start of the pandemic, COVID-19 remains a global health emergency. Although the immune response against SARS-CoV-2 has been extensively studied, some points remain controversial. One is the role of antibodies in viral clearance and modulation of disease severity. While passive transfer of neutralizing antibodies protects against SARS-CoV-2 infection in animal models, titers of anti-SARS-CoV-2 antibodies have been reported to be higher in patients suffering from more severe forms of the disease. A second key question for pandemic management and vaccine design is the persistence of the humoral response. Here, we characterized the antibody response in 187 COVID-19 patients, ranging from asymptomatic individuals to patients who died from COVID-19, and including patients who recovered. We developed in-house ELISAs to measure titers of IgG, IgM and IgA directed against the RBD or N regions in patient serum or plasma, and a spike-pseudotyped neutralization assay to analyse seroneutralization. Higher titers of virus-specific antibodies were detected in patients with severe COVID-19, including deceased patients, compared to asymptomatic patients. This demonstrates that fatal infection is not associated with defective humoral response. Finally, most of recovered patients still had anti-SARS-CoV-2 IgG more than 3 months after infection.

Diagnosis and Treatment of Vulvo-Perineal Endometriosis: A Systematic Review.

Objective: To describe the available knowledge on vulvo-perineal endometriosis including its diagnosis, clinical management and recurrence rate. Methods: We followed the PRISMA guidelines for Systematic Reviews and our study was prospectively registered with PROSPERO (CRD42020202441). The terms "Endometriosis" and "Perineum" or "Vulva" were used as keywords. Cochrane Library, Medline/Pubmed, Embase and Clinicaltrials.gov were searched. Papers in English, Spanish, Portuguese, French or Italian from inception to July 30, 2020 were considered. Reference lists of included articles and other literature source such as Google Scholar were also manually scrutinized in order to identify other relevant studies. Two independent reviewers screened potentially eligible studies according to inclusion criteria. Results: Out of 539 reports, 90 studies were eligible including a total of 283 patients. Their mean age was 32.7 ± 7.6 years. Two hundred sixty-three (95.3%) presenting with vulvo-perineal endometriosis have undergone either episiotomy, perineal trauma or vaginal injury or surgery. Only 13 patients (4.7%) developed vulvo-vaginal endometriosis spontaneously i.e., without any apparent condition favoring it. The reasons that motivated the patients to take medical advice were vulvo-perineal cyclical pain increasing during menstruations (98.2% of the patients, n = 278). Out of the 281 patients for whom a clinical examination was described, 274 patients (97.5%) showed a vulvo-perineal nodule, mass or swelling while six presented with bluish cutaneous lesions (2.1%) and 1 with bilateral polyps of the labia minora (0.4%). All but one patients underwent surgical excision of their lesions but only 88 patients (28.1%) received additional hormonal therapy. The recurrence rate was 10.2% (29 patients) considering a median follow-up period of 10 months (based on 61 studies). Conclusion: In conclusion, vulvo-perineal endometriosis is a rare entity with approximately 300 cases reported in the literature since 1923. With the available knowledge shown in this systematic review, we encourage all practitioners to think about perineal endometriosis in case of perineal cyclical pain with or without previous perineal damage. Diagnosis should be done with clinical exam, perineal ultrasound and pelvic MRI when available. In case of anal sphincter involvement, perianal ultrasound should be performed. Surgical excision of the lesion should be realized in order to remove the lesion and to confirm the diagnosis histologically. Hormonal treatment could be proposed to attempt to decrease the size of a large lesion before surgery or to avoid recurrence of the lesion. As evidence-based approach to the diagnosis, treatment and recurrence rate of affected patients remains a challenge given its low prevalence, the variations in management found in the articles included and the limited quality of available studies, we suggest that a prospective database on vulvo-perineal endometriosis should be generated to increase knowledge but also awareness among healthcare professionals and optimize patients' care. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42020202441.

Hibernoma-like Changes and TFE3 Expression in Mesothelioma Mimicking TFE3-Translocation Renal Cell Carcinoma: A Diagnostic Pitfall.

The long delay between asbestos exposure and the development of mesothelioma will likely result in an increased incidence of mesothelioma in our industrialized societies. Radiation therapy is another factor known to induce these tumors. We describe a rare case of foamy looking mesothelioma in a 63-year-old patient with a long oncology history of a supposed peritoneal carcinomatosis. The pathologist was faced with a diagnostic pitfall as this peritoneal clear cell tumor expressed transcription factor binding to immunoglobulin heavy constant mu enhancer 3 (TFE3) at the nuclear level. Fortunately, the pathologist performed an extensive panel of immunomarkers, leading to a final diagnosis of epithelioid mesothelioma. Thus, we describe the first case of mesothelioma expressing TFE3. Note that there was no rearrangement of TFE3 in fluorescence in situ hybridization.

Voiding recovery after radical parametrectomy in cervical cancer patients: An international prospective multicentre trial - SENTIX.

OBJECTIVE: Voiding dysfunctions represent a leading morbidity after radical hysterectomy performed in patients with early-stage cervical cancer. The aim of this study was to perform ad hoc analysis of factors influencing voiding recovery in SENTIX (SENTinel lymph node biopsy in cervIX cancer) trial. METHODS: The SENTIX trial (47 sites, 18 countries) is a prospective study on sentinel lymph node biopsy without pelvic lymphadenectomy in patients with early-stage cervical cancer. Overall, the data of 300 patients were analysed. Voiding recovery was defined as the number of days from surgery to bladder catheter/epicystostomy removal or to post-voiding urine residuum ≤50 mL. RESULTS: The median voiding recovery time was three days (5th-95th percentile: 0-21): 235 (78.3%) patients recovered in <7 days and 293 (97.7%) in <30 days. Only seven (2.3%) patients recovered after >30 days. In the multivariate analysis, only previous pregnancy (p = 0.033) and type of parametrectomy (p < 0.001) significantly influenced voiding recovery >7 days post-surgery. Type-B parametrectomy was associated with a higher risk of delayed voiding recovery than type-C1 (OR = 4.69; p = 0.023 vs. OR = 3.62; p = 0.052, respectively), followed by type-C2 (OR = 5.84; p = 0.011). Both previous pregnancy and type C2 parametrectomy independently prolonged time to voiding recovery by two days. CONCLUSIONS: Time to voiding recovery is significantly related to previous pregnancy and type of parametrectomy but it is not influenced by surgical approach (open vs minimally invasive), age, or BMI. Type B parametrectomy, without direct visualisation of nerves, was associated with longer recovery than nerve-sparing type C1. Importantly, voiding dysfunctions after radical surgery are temporary, and the majority of the patients recover in less than 30 days, including patients after C2 parametrectomy.

Experience With Medical Treatment of Cesarean Scar Ectopic Pregnancy (CSEP) With Local Ultrasound-Guided Injection of Methotrexate.

Objective: Ectopic pregnancy within Cesarean section scars is a rare condition. Late diagnosis carries significant risk of bleeding with poor prognosis for survival. There is no consensus on the management of this type of pregnancy. Historically, our facility offered an intra-muscular injection of methotrexate that resulted in a significant failure rate and later need for surgery. We hypothesized that injecting methotrexate directly into the gestational sac would improve the success rate of the treatment. Patients and Methods: This retrospective, uni-centric study examined nine patients aged between 33 and 42 years (mean age = 36.5 years) with Cesarean scar ectopic pregnancy (CSEP) between 2010 and 2018. CSEP was diagnosed by transvaginal ultrasound at a mean gestational age of 8w0/7. CSEP was treated under general anesthetic by ultrasound-guided methotrexate injection directly into the gestational sac. HCG levels and subsequent childbearing were monitored post-treatment. Results: Half of the patients were asymptomatic at the time of diagnosis. All patients tolerated treatment well and all ectopic pregnancies were successfully removed. HCG levels returned to negative within 3 months without additional medical or surgical intervention. The post-treatment pregnancy rate was 50%. Discussions/Conclusions: Our findings indicate that local ultrasound-guided injection of methotrexate into the gestational sac is a safe and effective therapeutic approach when performed by a trained team on a hemodynamically stable patient in the early stages of CSEP.

Hysteroscopic Resection for Missed Abortion: Feasibility, Operative Technique and Potential Benefit Compared to Curettage.

Objective: To evaluate the feasibility of hysteroscopic resection (HsR) for primary surgical management of missed abortion. Reproductive outcomes and potential benefit of this technique will be compared to traditional dilatation and curettage (D&C). Design: Retrospective cohort study in two Departments (Gynecology and Obstetrics) of a tertiary medical care center (Canadian Task Force classification II-2). Patients: Women with first trimester missed abortion. Intervention: Two techniques were used for the management of missed abortion: ultrasound-guided dilatation and curettage (D&C) and hysteroscopic resection (HsR). Results: We evaluated 358 patients who underwent primary surgical removal of missed abortion. Hundred seventy three patients have been treated by D&C and 185 underwent HsR. In the HsR group, 110 patients (59.5%) have obtained their pregnancy with in vitro fertilization (IVF) vs. 7 patients (4.0%) in the D&C group which make the HsR population hypofertile in comparison to the D&C population. The intra- and post-operative complication rates are low and comparable. Intrauterine anomalies were diagnosed during the HsR in 10 patients (5.4%) and could be investigated after the intervention as a possible cause of miscarriage. Because of the difference in term of fertility, the reproductive outcomes have been analyzed by multivariate analysis. The hazard ratio of pregnancy at 6 months, adjusted to the factor IVF for D&C compared to HsR is 0.69 [0.49-0.96] (p = 0.026). That could represent a significant benefit in the particular population followed in IVF, but regarding the retrospective analysis, and the very different population in the two groups, it doesn't allow us to draw any evidence based conclusion. Conclusion: Hysteroscopic resection is a feasible and safe procedure for the management of missed abortion that could increase the diagnosis of uterine abnormalities. With all the limitation of the design of our study, our data seems to show a trend to a potential benefit in term of reproductive outcomes for hypofertile patient undergoing IVF treatment.

Central Pathology Review in SENTIX, A Prospective Observational International Study on Sentinel Lymph Node Biopsy in Patients with Early-Stage Cervical Cancer (ENGOT-CX2).

The quality of pathological assessment is crucial for the safety of patients with cervical cancer if pelvic lymph node dissection is to be replaced by sentinel lymph node (SLN) biopsy. Central pathology review of SLN pathological ultrastaging was conducted in the prospective SENTIX/European Network of Gynaecological Oncological Trial (ENGOT)-CX2 study. All specimens from at least two patients per site were submitted for the central review. For cases with major or critical deviations, the sites were requested to submit all samples from all additional patients for second-round assessment. From the group of 300 patients, samples from 83 cases from 37 sites were reviewed in the first round. Minor, major, critical, and no deviations were identified in 28%, 19%, 14%, and 39% of cases, respectively. Samples from 26 patients were submitted for the second-round review, with only two major deviations found. In conclusion, a high rate of major or critical deviations was identified in the first round of the central pathology review (28% of samples). This reflects a substantial heterogeneity in current practice, despite trial protocol requirements. The importance of the central review conducted prospectively at the early phase of the trial is demonstrated by a substantial improvement of SLN ultrastaging quality in the second-round review.

Added value of para-aortic surgical staging compared to 18F-FDG PET/CT on the external beam radiation field for patients with locally advanced cervical cancer: An ONCO-GF study.

OBJECTIVE: Extended field chemoradiation is recommended for patients with locally advanced cervical cancer (LACC) and para-aortic lymph node (PALN) metastases. The radiation planning may be based on PET/CT while others recommend to rely on surgical staging. We report the rate of patients for whom the radiation field defined on PET/CT was modified by the histological PALN status. METHODS: Between March 2010 and December 2016, 168 consecutive patients with LACC underwent a pre-therapeutic PET/CT and PALN dissection. The data were reviewed retrospectively. The diagnostic performance of the PET/CT for definition of PALN status was calculated. We determined the percentage of patients for whom PALN dissection altered the external beam radiotherapy (EBRT) field defined on the PET/CT basis. RESULTS: Of 151 patients with negative PALNs on PET/CT, 26 had histological PALN metastases. Of 17 patients with positive PALNs on PET/CT, 9 were negative on histology of which 7 were located in the common iliac region. Sensitivity, specificity, positive and negative predictive value of PET/CT were 23.5, 93.3, 47.1 and 82.8% respectively. In total, 35 out of 168 patients underwent EBRT - field adaptation (pelvic vs extended field). The rate of radiation field modification (27,7%) was particularly high in the subgroup of patients with metastatic pelvic lymph nodes (PLNs) on PET/CT. CONCLUSION: Para-aortic surgical staging contributes significantly to individualize the radiation treatment of patients with LACC, particularly for those with positive PLNs at PET/CT. Indication of surgical staging deserves particular attention when the PET/CT suggests positive LNs in the common iliac region.

Effect on surgical decisions: Ulipristal acetate as key player in Belgian phase IV registration trial.

OBJECTIVE: To observe alterations in surgical planning that were due to the use of ulipristal acetate (UPA) 5 mg daily for symptomatic uterine fibroids. METHODS: A prospective cohort trial involving women with symptomatic fibroids was undertaken in 23 clinical practice sites within Belgium between October 1, 2014, and March 31, 2016, to compare initial surgical planning to performed surgical procedures following the use of UPA 5 mg daily for 3 months. Secondary outcomes were surgical complications, reduction in fibroids, bleeding control, and adverse effects. RESULTS: Two hundred and twenty-two women were recruited for the trial. The requirement for surgery decreased with the use of UPA, with 54% of women undergoing surgery after treatment. The reduction in surgery performed was lower for women willing to conceive (40%) compared to women who were not (49%). The volume of the fibroids decreased significantly, with the largest measured fibroid decreasing by 50%. Bleeding and pain were significantly decreased with the use of UPA. No major complications were recorded, and no liver function abnormalities were reported during the treatment and in follow-up. CONCLUSION: By administering UPA, the required rate of surgery was significantly decreased. Also, the resulting reduction in size of the fibroids could have the potential benefit of reducing surgery-related complications, and long-term use may be warranted to avoid surgery completely.

Fertility Sparing Treatment in Patients With Early Stage Endometrial Cancer, Using a Combination of Surgery and GnRH Agonist: A Monocentric Retrospective Study and Review of the Literature.

Objectives: To evaluate the efficacy and safety of gonadotropin-releasing hormone (GnRH) agonist after endometrial resection in women suffering early stage endometrial carcinoma (EC) and/or endometrial intra-epithelial neoplasia (EIN). Design: A retrospective review of clinical files between January 1999 and December 2016. Setting: University hospital. Patients: Eighteen women younger than 41 years with grade 1 endometrial carcinoma (G1EC) and/or Endometrial intra-epithelial neoplasia (EIN). INTERVENTIONS: All patients received GnRH agonist for 3 months after an endometrial resection combined with a laparoscopy to exclude concomitant ovarian tumor and/or other extra-uterine disease. The patient underwent a follow-up of 3 months interval with endometrial sampling by hysteroscopy. Main Outcome Measure(s): The recurrence rate and the pregnancy rate after fertility sparing treatment. Results: We identified 9 patients with EIN (50%), 7 patients with G1EC (38.9%), 1 with combined histology (5.5%), and 1 with G2EC (5.5%). After a median follow-up of 40.7 months, 12 patients conserved their uterus (66.7%), and 8 (53.3%) patients were pregnant with a total of 14 pregnancies among those who tried to become pregnant. We observed a complete response rate in 12 patients (66.7%) but 3 of these patients relapsed (25%). We also found a stable disease in 6 patients (33.3%). Conclusions: Compared with other fertility sparing treatments, GnRH agonist after surgery is an effective fertility-sparing strategy for women with EIN and/or G1EC. We recommend hysterectomy once a family has been completed even if the literature does not clearly lead to radical surgery.

Gene expression changes in uterine myomas in response to ulipristal acetate treatment.

RESEARCH QUESTION: Does ulipristal acetate (UPA) modify the expression of genes related to apoptosis or the extracellular matrix in uterine myomas and are any modifications associated with a clinical response? DESIGN: Targeted analysis of 176 apoptosis- or extracellular-matrix-related genes was conducted using polymerase chain reaction (PCR) arrays. Relevant results were validated by quantitative PCR. Four groups were established: responsive short-term (one course, n = 9), responsive long-term (two to four courses, n = 9), non-responsive (n = 9), and the control group who was not given any hormone therapy (n = 9). The clinical response was monitored by medical imagery and considered significant when volume reduction was greater than 25%. RESULTS: Compared with untreated myomas, significant changes in expression of four genes were found in UPA-treated myomas. Gene expression of integrin subunit beta 4 was repressed by UPA treatment (fold change [FC] = -12.50, P < 0.001, q < 0.001), tenascin-C expression was downregulated in UPA-responsive patients (FC = -2.50, P = 0.010, q = 0.090), survivin was repressed in short-term UPA-responsive tumours (FC = -7.69, P < 0.001, q = 0.010), and catenin delta 2 gene expression was upregulated in non-responsive myomas (FC = +7.36, P < 0.001, q = 0.010). CONCLUSION: This characterization provides the first molecular distinction between myomas responsive or non-responsive to UPA treatment.