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Patients with endometrial cancer differ in terms of the extent of T-cell infiltration; however, the association between T-cell subpopulations and patient outcomes remains unexplored. We characterized 285 early-stage endometrial carcinoma samples for T-cell infiltrates in a tissue microarray format using multiplex fluorescent immunohistochemistry. The proportion of T cells and their subpopulations were associated with clinicopathological features and relapse-free survival outcomes. CD3+ CD4+ infiltrates were more abundant in the patients with higher grade or non-endometrioid histology. Cytotoxic T cells (CD25+, PD-1+, and PD-L1+) were strongly associated with longer relapse-free survival. Moreover, CD3+ PD-1+ stromal cells were independent of other immune T-cell populations and clinicopathological factors in predicting relapses. Patients with high stromal T-cell fraction of CD3+ PD-1+ cells were associated with a 5-year relapse-free survival rate of 93.7% compared to 79.0% in patients with low CD3+ PD-1+ fraction. Moreover, in patients classically linked to a favorable outcome (such as endometrioid subtype and low-grade tumors), the stromal CD3+ PD-1+ T-cell fraction remained prognostically significant. This study supports that T-cell infiltrates play a significant prognostic role in early-stage endometrial carcinoma. Specifically, CD3+ PD-1+ stromal cells emerge as a promising novel prognostic biomarker.

Aim Our study aims to investigate the safety and effectiveness of sentinel lymph node biopsy using indocyanine green (ICG) for the surgical staging of early-stage endometrial cancer in comparison to technetium-99 m use. Methods We conducted an observational retrospective study with patients diagnosed of endometrial cancer and FIGO stages I-II. All participants were injected technetium-99m the day prior to the surgery and underwent lymphoscintigraphy along with single-photon emission computed tomography. In addition, all patients were administered intraoperatively ICG injection to detect sentinel lymph node biopsy. The surgical staging was then completed according to the European Society for Medical Oncology preoperative risk category. Data obtained from the analysis of technetium-99m detection was compared to ICG detection. Results A total of 53 women with endometrial cancer were included in the study, 49 (92.5%) of them showed drainage preoperatively in the single-photon emission computed tomography and/or lymphoscintigraphy. The intraoperative bilateral detection rate for technetium-99 m was 26 (49.1%) patients compared to 40 (75.5%) patients with ICG (p = 0.013). We observed a 42.5% increase in the mean number of lymph nodes retrieved by ICG compared to technetium-99m (2.85 vs 2,0 nodes; p = 0.002). We intraoperatively identified 164 lymph nodes, 104 (63.4%) located in both obturator areas and external iliac vessels. Conclusion The use of ICG for the performance of sentinel node biopsy in patients with endometrial cancer seems safe and could be superior to technetium-99 m, since it offers a higher bilateral detection rate and nodal retrieval, resulting in the possibility to perform safely less full staging lymphadenectomies.

Objective To determine whether the extraperitoneal approach for paraaortic staging lymphadenectomy results in a lower rate of surgical complications compared to the transperitoneal approach, without compromising oncological outcomes. Methods Prospective randomized multicenter study of patients with early endometrial or ovarian cancer undergoing paraaortic lymphadenectomy in 2010–2019. Patients were randomized to minimally invasive surgery (laparoscopy or robotic-assisted) using an extraperitoneal or a transperitoneal approach. The primary end point measure was a composite outcome that included developing one or more of the following surgical complications: bleeding during paraaortic lymphadenectomy ≥500 mL, any intraoperative complication related to paraaortic lymphadenectomy, severe postoperative complication (Dindo ≥ IIIA), impossibility to complete the procedure, or conversion to laparotomy. Results There were 103 patients in the extraperitoneal group and 100 in the transperitoneal group. Differences in the composite outcome (transperitoneal 26.0% vs, extraperitoneal 18.4%; P = 0.195) were not found. Differences in the operative time, conversion to laparotomy, intraoperative bleeding, or survival were not observed. A higher number of lymph nodes were retrieved through the extraperitoneal approached (median, interquartile range [IQR] 12 [7–17] vs, 14 [10–19]: P = 0.026). Older age and greater body mass index (BMI) or waist-to-hip ratio (WHR) increased the risk for surgical complications independently of the laparoscopic approach. Conclusions The extraperitoneal approach did not show differences regarding surgical and oncological parameters compared with the transperitoneal approach, although the number of aortic nodes retrieved was higher. The decision to use one or another laparoscopic route is a matter of the surgeon preference. Trial registration ClinicalTrials.gov .identifier: NCT02676726

Objective Paraaortic lymph node involvement is an important prognostic factor in locally advanced cervical cancer (LACC), but the anatomic limit of aortic lymphadenectomy is controversial. We assessed the impact of extraperitoneal paraaortic lymphadenectomy up to the left renal vein in patients with LACC undergoing pretherapeutic staging. Methods A retrospective, multicenter study of patients with LACC stages FIGO 2009 IB2 and IIA2-IVA treated in 10 Spanish reference hospitals in gynecological oncology between 2000 and 2016. Sites of metastatic paraaortic lymph nodes above or below the inferior mesenteric artery were evaluated. Procedural-related intraoperative and early and late complications were assessed. Results We included 634 patients undergoing paraaortic lymphadenectomy, in 616 (97.2%) of which the left renal vein was the upper limit of dissection (laparoscopy 592, robotic-assisted 24). The median surgical time was 150 min (interquartile range (IQR) 120–180), blood loss was 50 mL (range 20–80), and the length of stay was 2 days (range 2–3). Metastatic paraaortic involvement was found in 114 patients (18.5%), with infrarenal metastases in 73 (64%) of them. There were 11 patients (9.6%) with infrarenal metastases only, whereas in the remaining 62 (54.4%) patients concomitant infrarenal and inframesenteric metastases were observed. Intraoperative, early, and late postoperative complications occurred in 3.6%, 7.0%, and 4.5% of patients, respectively. Conclusions In this study of patients with LACC undergoing surgical staging, paraaortic lymphadenectomy up to the left renal vein detected skip or isolated infrarenal metastasis in 9.6% of patients, with an acceptable surgical morbidity.

There are three prognostic stratification tools used for endometrial cancer: ESMO-ESGO-ESTRO 2016, ProMisE, and ESGO-ESTRO-ESP 2020. However, these methods are not sufficiently accurate to address prognosis. The aim of this study was to investigate whether the integration of molecular classification and other biomarkers could be used to improve the prognosis stratification in early-stage endometrial cancer. Relapse-free and overall survival of each classifier were analyzed, and the c-index was employed to assess accuracy. Other biomarkers were explored to improve the precision of risk classifiers. We analyzed 293 patients. A comparison between the three classifiers showed an improved accuracy in ESGO-ESTRO-ESP 2020 when RFS was evaluated (c-index = 0.78), although we did not find broad differences between intermediate prognostic groups. Prognosis of these patients was better stratified with the incorporation of CTNNB1 status to the 2020 classifier (c-index 0.81), with statistically significant and clinically relevant differences in 5-year RFS: 93.9% for low risk, 79.1% for intermediate merged group/CTNNB1 wild type, and 42.7% for high risk (includ-ing patients with CTNNB1 mutation). The incorporation of molecular classification in risk stratification resulted in better discriminatory capability, which could be improved even further with the addition of CTNNB1 mutational evaluation, This research was funded by the Instituto de Salud Carlos III (ISCIII), cofinanced by the European Development Regional Fund ‘A way to achieve Europe’ (FEDER, PI17/01723 to D.H.), and by Academy of Finland grant (No. 317680 to J.T.). B.Z. is supported by the faculty funded PhD position in the Integrative Life Science Doctoral Programme, University of Helsinki

Introduction/Background*The impact of the COVID-19 pandemic on Spanish hospitals over the past year has forced healthcare institutions to make drastic changes in the management of oncology patients. The main objective of this study is to describe the changes in ambulatory attendance of patients with gynecological cancer and the ease of contact with the gynaecological oncology section reported by users.MethodologyThe GineonCoVID study is a multicenter Spanish study that collect data from a national survey. The anonymous survey consists of 23 questions regarding the personal experience of the patient and modifications in health care during follow up of patient with gynecological malignancies from April to May 2021. The survey has been divided into 3 sections. In this sub-analysis, questions regarding follow-up modifications and the perspective of the patients with gynecological cancer about changes were analyzed.Result(s)*376 patients responded to the survey. The median age was 58 years. 43% of the patients were diagnosed with endometrial cancer, 27.3% with ovarian cancer and 24.1% with cervical cancer. 85% of the patients had an appointment that was delayed by the pandemic. 67.7% considered that the situation justified the delay of the appointment. 93.3% who contacted the gynecological oncology unit were able to solve the problem by telephone. Upon entering the consultation, 41.3% were questioned about COVID symptoms or contacts. 97.6% considered that adequate measures were taken to avoid contagion during the medical visit. Regarding how they would value the care received (scale of 1–10), 2.2% scored it with a 7;6.7% with 8;23.2% with 9 and 67.7% with 10.Conclusion*The COVID-19 pandemic and the redistribution of health system resources have forced the development of variations in the assistance and follow-up patients with gynecological cancer in order to decrease the number of hospital visits and minimize the risk of infection. Telephone consultations and delay in routinary tests were very useful tools during this period without compromising the quality of care.

Introduction/Background* The aim of our study is to evaluate the oncological and perinatal outcomes in young women diagnosed with atypical endometrial hyperplasia (AEH) or endometrial cancer (EC) treated with hormone therapy. Methodology A single institutional ambispective study was performed including all patients diagnosed with AEH or EC grade 1 without myometrial invasion who received hormone therapy between January 2011 and July 2021. We analyzed the complete response rate and recurrence rate of disease and pregnancy rate in these patients as well as perinatal results (live births rate, type of delivery and perinatal morbidity). In addition, we evaluated complete response rate according to type of hormone therapy, dosage received and treatment length. A review of literature was performed to identify studies involving patients with AEH or EC who received fertility sparing management. All statistical analysis were performed using the software SPSS Statistics v.24.0 (IBM Corp., Armonk, NY, USA). Result(s)* The results after final statistical analysis will be available when we complete the collection of follow-up data for conservatively treated patients. Conclusion* Conservative management with progestins of young patients with AEH or EC grade 1 limited to the endometrium is an acceptable possibility given the high remission rate and live birth rates achieved. However, definitive surgical treatment cannot be avoided given the high recurrence rate described in the literature.

Introduction/Background* The surgical approach of minimally invasive surgery (MIS) for paraaortic staging lymphadenectomy (PALND) in gynecologic malignancies is controversial. The STELLA-2 trial was designed to determine whether the extraperitoneal approach for PALND results in a lower rate of surgical complications compared to the transperitoneal approach. Methodology Prospective randomized multicenter study of patients with early-stage endometrial or ovarian cancer who underwent PALND as part of the staging process between June 2012 and January 2019. Patients were randomized to PALND by MIS (laparoscopy or robotic-assisted) using an extraperitoneal or a transperitoneal approach. The primary end point measure was a composite outcome that included developing one or more of the following surgical complications: bleeding during paraaortic lymphadenectomy ≥ 500 mL, any intraoperative complication related to paraaortic lymphadenectomy, severe postoperative complication (Dindo ≥ IIIA), impossibility to complete the procedure, or conversion to laparotomy. Secondary end points included the number of lymph nodes retrieved, the operative time, the length of hospital stay, and oncologic outcome (overall survival and disease-free survival). A post-hoc analysis to compare all possible approaches (transperitoneal or extraperitoneal, robotic-assisted or laparoscopic) was performed. ClinicalTrials gov id:NCT02676726). Result(s)* Of 209 women randomized, 103 in the extraperitoneal group and 100 in the transperitoneal group underwent PALND. Differences in the composite outcome between both groups (transperitoneal 26.0% vs extraperitoneal 18.4%: P=.195) were not found. A higher number of lymph nodes were retrieved through the extraperitoneal approached (median, interquartile range [IQR] 12 [7-17] vs 14 [10-19]: P=.026). Differences in the operative time, conversion to laparotomy, intraoperative bleeding, or survival were not observed. The post-hoc multivariable analysis revealed that age (OR: 1.05, 95% CI: 1.00-1.09), body mass index (OR: 1.09, 95% CI: 1.03-1.16), and waist-hip ratio (OR: 1.66, 95% CI: 1.12-2.47) were found to independently increase the risk of PALND complications, while extraperitoneal robotic approach (OR: 0.13, 95% CI 0.02-0.64) was an independent protective factor for complication occurrence. Conclusion* Extraperitoneal approach is a safe procedure for PALND in the minimally invasive surgical staging of women diagnosed with early-stage endometrial or ovarian malignancy. Moreover, in the post-hoc analysis, robotic-assisted extraperitoneal PALND was associated with fewer surgical complications.

According to the World Health Organization (WHO), men and women older than 50 years present osteoporosis with reduced bone mass, this is one of the major impact morbidities causes in the world. It may be present in the hip, spine, and wrist. The gold standard technique for osteoporosis diagnosis is the Bone Densitometry (DXA). The evaluation of an electroacoustic device is as an alternative procedure for the validation and diagnosis of osteoporosis. Diagnosis of osteoporosis severity was carried out in 49 females by using the registers of the DEXA’s T-Score values. These were statistically compared with the measurements performed using the electroacoustic device. Non-Significative difference between measurements was found with ANOVA and Chi-square tests and the area for the ROC curve on electroacoustic devices was 0.551. The Bland Altman suggests an excellent concordance between both techniques. This is a non-invasive method that has a proper match with the gold standard. The study suggests that procedure measurements with the electroacoustic device could be implemented as an alternative clinical practice for osteoporosis diagnosis.

Tatton-Brown-Rahman (TBRS) syndrome is a recently described overgrowth syndrome caused by loss of function variants in the DNMT3A gene. This gene encodes for a DNA methyltransferase 3 alpha, which is involved in epigenetic regulation, especially during embryonic development. Somatic variants in DNMT3A have been widely studied in different types of tumors, including acute myeloid leukemia, hematopoietic, and lymphoid cancers. Germline gain-of-function variants in this gene have been recently implicated in microcephalic dwarfism. Common clinical features of patients with TBRS include tall stature, macrocephaly, intellectual disability (ID), and a distinctive facial appearance. Differential diagnosis of TBRS comprises Sotos, Weaver, and Malan Syndromes. The majority of these disorders present other clinical features with a high clinical overlap, making necessary a molecular confirmation of the clinical diagnosis. We here describe seven new patients with variants in DNMT3A, four of them with neuropsychiatric disorders, including schizophrenia and psychotic behavior. In addition, one of the patients has developed a brain tumor in adulthood. This patient has also cerebral atrophy, aggressive behavior, ID, and abnormal facial features. Clinical evaluation of this group of patients should include a complete neuropsychiatric assessment together with psychological support in order to detect and manage abnormal behaviors such as aggressiveness, impulsivity, and attention deficit-hyperactivity disorder. TBRS should be suspected in patients with overgrowth, ID, tall stature, and macrocephaly, who also have some neuropsychiatric disorders without any genetic defects in the commonest overgrowth disorders. Molecular confirmation in these patients is mandatory., This project was supported by ISCII, FEDER funds grant: FIS-PI15/01481.

Objective To compare the performance of magnetic resonance imaging (MRI) and transvaginal ultrasound (TVU) in detecting deep infiltrating endometriosis (DIE), using Enzian classification. Secondarily, to evaluate the influence of nodule size on the accuracy of MRI and TVU. Methods A retrospective study was carried out at "La Paz" University Hospital, Madrid, Spain, between April 2012 and December 2014. Inclusion criteria were suspicion of DIE at gynecologic examination, indication to undergo TVU, MRI and surgery. Exclusion criteria were previous hysterectomy, bowel resection, or urinary tract surgery. The diagnosis of DIE using MRI or TVU was considered positive when it correlated with histology. Sensitivity, specificity, accuracy, and mean size of the nodule were calculated. Results In the present study involving 48 women, TVU demonstrated greater accuracy than MRI for recto-vaginal (77% vs 69%) and vaginal (94% vs 89%) endometriosis. MRI showed greater accuracy (96%) than TVU (92%) for bladder endometriosis. The size of the nodule did not have a significantly different effect on the accuracy of TVU compared with MRI. Conclusion In the present study, TVU provided a more accurate localization of vaginal and recto-vaginal endometriosis as compared with MRI; however, MRI should be recommended if a suspicion of bladder endometriosis exists. The nodule size did not seem to influence the accuracy of the two techniques.

Procediments quirúrgics de citoreducció; Teràpia neoadjuvant; Neoplàsies d'ovari Procedimientos quirúrgicos de citorreducción; Terapia neoadyuvante; Neoplasias de ovario Cytoreduction Surgical Procedures; Neoadjuvant Therapy; Ovarian Neoplasms Objective We sought to evaluate the impact on survival of tumor burden and surgical complexity in relation to the number of cycles of neoadjuvant chemotherapy (NACT) in patients with advanced ovarian cancer (OC) with minimal (CC-1) or no residual disease (CC-0). Methods This retrospective study included patients with International Federation of Gynaecology and Obstetrics IIIC–IV stage OC who underwent debulking surgery at 4 high-volume institutions between January 2008 and December 2015. We assessed the overall survival (OS) of primary debulking surgery (PDS group), early interval debulking surgery after 3–4 cycles of NACT (early IDS group) and delayed debulking surgery after 6 cycles (DDS group) with CC-0 or CC-1 according to peritoneal cancer index (PCI) and Aletti score. Results Five hundred forty-nine women were included: 175 (31.9%) had PDS, 224 (40.8%) early IDS and 150 (27.3%) DDS. Regardless of Aletti score, median OS after PDS was significantly higher than after early IDS or DDS, but the survival difference was higher in women with an Aletti score 10, there were no differences between PDS and early IDS, but DDS was associated with decreased OS. Conclusion The benefit of complete PDS compared with NACT was maximal in patients with a low complexity score. In patients with low tumor burden, there was a survival benefit of PDS over early IDS or DDS. In women with high tumor load, DDS impaired the oncological outcome. The project that gave rise to these results received the support of a fellowship from “la Caixa” Foundation (ID 100010434). The fellowship code is LCF/BQ/EU18/11650038.

The objective of this study was to evaluate the efficacy of one-step nucleic acid amplification (OSNA) for the detection of sentinel lymph node (SLN) metastasis compared to standard pathological ultrastaging in patients with early-stage endometrial cancer (EC). A total of 526 SLNs from 191 patients with EC were included in the study. 379 SLNs (147 patients) were evaluated by both methods, OSNA and standard pathological ultrastaging. The central 1-mm portion of each lymph node was subjected to semi-serial sectioning at 200-μm intervals and examined by hematoxylin-eosin and immunohistochemistry with CK19; the remaining tissue was analysed by OSNA for CK19 mRNA. The OSNA assay detected metastases in 19.7% of patients (14.9% micrometastasis and 4.8% macrometastasis), whereas pathological ultrastaging detected metastasis in 8.8% of patients (3.4% micrometastasis and 5.4% macrometastasis). Using the established cut-off value for detecting SLN metastasis by OSNA in EC (250 copies/μl), the sensitivity of the OSNA assay was 92%; specificity was 82%; diagnostic accuracy was 83%, and the negative predictive value was 99%. Discordant results between both methods were recorded in 20 patients (13.6%). OSNA resulted in an upstaging in 12 patients (8.2%). OSNA could aid in the identification of patients requiring adjuvant treatment at the time of diagnosis.

Objective: To evaluate the reliability of sagittal abdominal diameter (SAD)—a surrogate of visceral obesity—in MRI, and its accuracy to predict the surgical morbidity of aortic lymphadenectomy. Design: A multicentre reliability (phase 1) and accuracy (phase 2) cohort study. Setting: Three Spanish referral hospitals. Population: High-risk endometrial cancer patients undergoing minimally invasive surgical staging. Patients were classified into subgroups: conventional vs. robotic-assisted laparoscopy, and transperitoneal vs. extraperitoneal technique. Methods: Retrospective analysis of data from the STELLA-2 randomized controlled trial. In the first phase, we measured the agreement of three SAD measurements (at the umbilicus, the renal vein, and the inferior mesenteric artery) and selected the most reliable one. In phase two, we evaluated the diagnostic accuracy of SAD to predict surgical morbidity. Main Outcome Measures: surgical morbidity was defined by a core outcome set including variables related to blood loss, operative time, surgical complications, and para-aortic lymphadenectomy difficulty. Results: In phase one, all measurements showed good inter-rater and intra-rater agreement. Umbilical SAD was the most reliable one. In phase two, we included 136 patients. Umbilical SAD had a good diagnostic accuracy to predict surgical morbidity in patients undergoing transperitoneal laparoscopic lymphadenectomy (0.73 in ROC curve). It performed better than BMI and other anthropometric measurements. We calculated a cut-off point of 246 mm (sensitivity: 0.56 and specificity: 0.80). Conclusions: Umbilical SAD is a simple, reliable, and potentially useful measurement to predict surgical morbidity in endometrial cancer patients undergoing minimally invasive surgical staging, especially when facing transperitoneal aortic lymphadenectomy.

ObjectiveTo evaluate the role of sentinel lymph node biopsy (SLNB) to avoid staging lymphadenectomies by detecting nodal metastasis in intermediate- and high-risk endometrial cancer (EC).MethodsA single institutional retrospective study was performed including all patients with intermediate- and high-risk EC who underwent surgical nodal staging between January 2012 and December 2019. Patients with disseminated disease detected on imaging techniques or at the time of surgery were excluded. Patients were evaluable if they underwent nodal staging with SLNB and pelvic (PLD) and paraaortic (PALD) lymph node dissection. We analyzed the accuracy of the sentinel lymph node technique. Only patients with at least one sentinel lymph node (SLN) detected were included in the sensitivity and negative predictive value (NPV) analyses. The tracers used were technetium 99m, blue dye, and indocyanine green.ResultsEighty-eight patients presented intermediate- and high-risk EC (51 patients and 37 patients respectively) and underwent SLNB with consecutive PLD and PALD. The median (range) number of sentinel nodes retrieved was 2.9 (0–11). The global detection rate of SLN was 96.6% with a bilateral detection of 80.7% when considering all tracers used. However, when combination of indocyanine green and technetium was used the bilateral detection rate was 90.3%. Nodal metastases were detected in 17 (19.3%) cases, 8 (47%) of them corresponded to low volume metastasis (LVM), 7 (87.5%) of them diagnosed at ultrastaging pathologic exam. Finally, we obtained a sensitivity of 90%, a NPV of 97.5%, and a false negative rate (FNR) of 10% in the intermediate-risk EC compared to sensitivity of 85.7%, NPV of 96.6%, and FNR of 14.3% in the high-risk EC group. The only patient with isolated paraaortic nodal metastasis was found at the high-risk group, 1.1%.ConclusionsAccording to our results, full lymphadenectomy could be avoided by performing SLNB in patients with intermediate-risk EC because the only false negative case detected was at the beginning of ICG learning curve. For high-risk EC patients we did not find enough evidence to support the systematic avoidance of staging full lymph node dissection. Nevertheless, SLNB should be performed in all cases of EC as it improves LVM diagnosis substantially.

Our aim was to analyze the association between anal human papillomavirus (HPV) infection and abnormal anal cytology in women with high-grade cervical intraepithelial neoplasia (CIN 2+). We also analysed what other risk factors might be significant. We carried out a prevalence study from April 2015 to March 2017 at La Paz University Hospital. Genotyping of HPV, anal cytology and high-resolution anoscopy were performed. Of 171 patients recruited, 53 cases (31%) were diagnosed as histological CIN 2+: there were no statistically significant differences in the prevalence of anal HPV (OR = 0.8), nor the prevalence of abnormal anal cytology (OR = 2.15, 95% CI 0.8-5.7) compared to women with CIN 1 or no cervical dysplasia. Immunosuppression (OR = 2.51, 95% CI 1-6.3, p < .05), cervical HPV (OR = 3.9, 95% CI 1.9-8.0, p < .01) and being older than 40 years old (p < .05) were also associated with anomalous anal results. Impact Statement What is already known on this subject? Anal HR-HPV and abnormal anal cytology may precede anal intraepithelial neoplasia (AIN): a premalignant lesion that may progress to anal cancer. It is known that there are four populations which present a higher risk of developing anal cancer compared to the general population: human immunodeficiency virus (HIV)-positive patients, other immunocompromised populations, men who have sex with men and women with a history of disease secondary to HPV infection. What do the results of this study add? This study allowed us to compare the prevalence of anal HPV and abnormal anal cytology in women with CIN 2+: it analysed whether these women already presented alterations in anal tests at the moment of the diagnosis of the preneoplastic cervical lesion. It also provides information for the management of the populations at a higher risk of developing anal cancer; specifically, the group of women with a prior history of HPV-associated anogenital disease. What are the implications of these findings for clinical practice and/or further research? Our findings improve the existing evidence on anal HPV infection and anal cytology on the least studied population at risk. Data could be useful for further research in order to clarify the role of anal screening in this population and standardise the clinical practice.

Resumen En situación de pandemia, los tres principios básicos en la atención sanitaria son priorizar los recursos, mantener el confinamiento del paciente para evitar la transmisión comunitaria y el colapso sanitario y reducir la asistencia no prioritaria con el fin de evitar la exposición del paciente y de salvaguardar la salud del profesional sanitario. El control antenatal debe mantenerse durante el periodo de crisis sanitaria, independientemente del estado de alerta COVID-19. La ecografía obstétrica en una prueba fundamental para la toma de decisiones clínicas durante el embarazo, con un impacto en el manejo del binomio madre-feto y en el resultado perinatal, por lo que se ha de garantizar su realización. Con el fin de reducir las visitas presenciales al mínimo número posible, estas se intentarán organizar teniendo en cuenta los controles ecográficos establecidos. Basados en la evidencia científica y en las principales guías nacionales e internacionales, hemos elaborado este documento que incluye las principales recomendaciones para el cuidado antenatal de la gestante en el contexto de la pandemia por SARS-CoV-2. En él se recoge cómo debe reestructurarse una Sección de Medicina Fetal ante esta nueva situación, qué medidas de seguridad deben seguirse para la realización de las exploraciones ecográficas y técnicas invasivas y de qué modo debe procederse para la limpieza y desinfección de los equipos ecográficos. Estas recomendaciones deberán adaptarse a los diferentes medios teniendo en cuenta la infraestructura del centro y sus recursos.

Low-grade and early-stage endometrioid endometrial carcinomas (EECs) have an overall good prognosis but biomarkers identifying patients at risk of relapse are still lacking. Recently, CTNNB1 exon 3 mutation has been identified as a potential risk factor of recurrence in these patients. We evaluate the prognostic value of CTNNB1 mutation in a single-centre cohort of 218 low-grade, early-stage EECs, and the correlation with beta-catenin and LEF1 immunohistochemistry as candidate surrogate markers. CTNNB1 exon 3 hotspot mutations were evaluated by Sanger sequencing. Immunohistochemical staining of mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6), p53, beta-catenin, and LEF1 was performed in representative tissue microarrays. Tumours were also reviewed for mucinous and squamous differentiation, and MELF pattern. Nineteen (8.7%) tumours harboured a mutation in CTNNB1 exon 3. Nuclear beta-catenin and LEF1 were significantly associated with CTNNB1 mutation, showing nuclear beta-catenin a better specificity and positive predictive value for CTNNB1 mutation. Tumours with CTNNB1 exon 3 mutation were associated with reduced disease-free survival (p = 0.010), but no impact on overall survival was found (p = 0.807). The risk of relapse in tumours with CTNNB1 exon 3 mutation was independent of FIGO stage, tumour grade, mismatch repair protein expression, or the presence of lymphovascular space invasion. CTNNB1 exon 3 mutation has a negative impact on disease-free survival in low-grade, early-stage EECs. Nuclear beta-catenin shows a higher positive predictive value than LEF1 for CTNNB1 exon 3 mutation in these tumours, This research was funded by the Instituto de Salud Carlos III (ISCIII) (PI17/01723), co-financed by the European Development Regional Fund ‘A way to achieve Europe’ (FEDER)

Objective. Despite radical surgery and chemotherapy, most patients with ovarian cancer die due to disease progression. M-Trap is an implantable medical device designed to capture peritoneal disseminated tumor cells with the aim to focalize the disease. This trial analyzed the safety and performance of the device. Methods. This first-in-human prospective, multi-center, non-blinded, single-arm study enrolled 23 women with high-grade serous advanced ovarian cancer. After primary or interval debulking surgery, 3 M-Trap devices were placed in the peritoneum of the abdominal cavity. 18-months post-implantation or at disease progression, devices were initially removed by laparoscopy. The primary safety endpoint was freedom from device and procedure-related major adverse events (MAEs) through 6-months post-implantation compared to an historical control. The primary performance endpoint was histopathologic evidence of tumor cells capture. Results. Only one major adverse event was attributable to the device. 18 women were free of device and pro-cedure related MAEs (78.3%). However, the primary safety endpoint was not achieved (p = 0.131), primarily at-tributable to the greater surgical complexity of the M-Trap patient population. 62% of recurrent patients demonstrated tumor cell capture in at least one device with a minimal tumor cell infiltration. No other long-term device-related adverse events were reported. The secondary performance endpoint demonstrated a lack of disease focalization. Conclusions. The M-Trap technology failed to meet its primary safety objective, although when adjusted for surgical complexity, the study approved it. Likewise, the devices did not demonstrate the anticipated benefits in terms of tumor cell capture and disease focalization in recurrent ovarian cancer. (c) 2021 Elsevier Inc. All rights reserved.

The objective of this study was to evaluate the efficacy of one-step nucleic acid amplification (OSNA) for the detection of sentinel lymph node (SLN) metastasis compared to standard pathological ultrastaging in patients with early-stage endometrial cancer (EC). A total of 526 SLNs from 191 patients with EC were included in the study, and 379 SLNs (147 patients) were evaluated by both methods, OSNA and standard pathological ultrastaging. The central 1 mm portion of each lymph node was subjected to semi-serial sectioning at 200 μm intervals and examined by hematoxylin–eosin and immunohistochemistry with CK19; the remaining tissue was analyzed by OSNA for CK19 mRNA. The OSNA assay detected metastases in 19.7% of patients (14.9% micrometastasis and 4.8% macrometastasis), whereas pathological ultrastaging detected metastasis in 8.8% of patients (3.4% micrometastasis and 5.4% macrometastasis). Using the established cut-off value for detecting SLN metastasis by OSNA in EC (250 copies/μL), the sensitivity of the OSNA assay was 92%, specificity was 82%, diagnostic accuracy was 83%, and the negative predictive value was 99%. Discordant results between both methods were recorded in 20 patients (13.6%). OSNA resulted in an upstaging in 12 patients (8.2%). OSNA could aid in the identification of patients requiring adjuvant treatment at the time of diagnosis., El objetivo de este estudio fue evaluar la eficacia de la amplificación de ácido nucleico en un solo paso (OSNA) para la detección de metástasis en el ganglio linfático centinela (GC) en comparación con la ultraestadificación patológica estándar en pacientes con cáncer de endometrio (CE) en estadio temprano. Se incluyeron en el estudio un total de 526 SLN de 191 pacientes con EC, y 379 SLN (147 pacientes) fueron evaluados por ambos métodos, OSNA y ultraestadificación patológica estándar. La porción central de 1 mm de cada ganglio linfático se sometió a un seccionamiento semiserie a intervalos de 200 μm y se examinó mediante hematoxilina-eosina e inmunohistoquímica con CK19; el tejido restante fue analizado por OSNA para ARNm de CK19. El ensayo OSNA detectó metástasis en el 19,7 % de los pacientes (14,9 % micrometástasis y 4,8 % macrometástasis), mientras que la ultraestadificación patológica detectó metástasis en el 8,8 % de los pacientes (3. 4% micrometástasis y 5,4% macrometástasis). Usando el valor de corte establecido para detectar metástasis SLN por OSNA en EC (250 copias/μL), la sensibilidad del ensayo OSNA fue del 92 %, la especificidad fue del 82 %, la precisión diagnóstica fue del 83 % y el valor predictivo negativo fue del 99 % Se registraron resultados discordantes entre ambos métodos en 20 pacientes (13,6%). OSNA resultó en una sobreestadificación en 12 pacientes (8,2%). OSNA podría ayudar en la identificación de pacientes que requieren tratamiento adyuvante en el momento del diagnóstico. Se registraron resultados discordantes entre ambos métodos en 20 pacientes (13,6%). OSNA resultó en una sobreestadificación en 12 pacientes (8,2%). OSNA podría ayudar en la identificación de pacientes que requieren tratamiento adyuvante en el momento del diagnóstico. Se registraron resultados discordantes entre ambos métodos en 20 pacientes (13,6%). OSNA resultó en una sobreestadificación en 12 pacientes (8,2%). OSNA podría ayudar en la identificación de pacientes que requieren tratamiento adyuvante en el momento del diagnóstico.

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 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.

International audience; Objective: To assess the survival benefit of primary debulking surgery (PDS) compared to interval debulking surgery (IDS) after complete cytoreduction (CC-0) or cytoreduction to minimal residual disease (CC-1) in advanced ovarian cancer. Secondary objective was to evaluate the effect of tumor load and surgical complexity on patients' survival.Methods: A retrospective multicentric study was designed, including patients with IIIC-IV FIGO stage ovarian cancer who underwent PDS or IDS with CC-0 or CC-1 from January 2008 to December 2015 in four high-volume institutions. Patients were classified in three groups: PDS, IDS after 3-4 cycles of neoadjuvant chemotherapy (NACT), and IDS after 6 cycles. Disease-free survival (DFS) and overall survival (OS) were estimated. Univariable and multivariable analyses were conducted.Results: We included 549 patients, 175 (31.9%) underwent PDS, 224 (40.8%) had IDS after 3-4 cycles of NACT, and 150 (27.3%) underwent IDS after 6 cycles. Median DFS in PDS, IDS at 3-4 cycles and IDS at 6 cycles were 23.0 months (95%CI = [20.0-29.3]), 18.0 months (95%CI = [15.9-20.0]) and 17.1 months (95%CI = [15.0-20.9]), respectively; p < .001. Median OS were 84.0 months (95%CI = [68.3-111.0]), 50.7 months (95%CI = [44.6-59.5]) and 47.5 months (95%CI = [39.3-52.9]), respectively; p < .001. In multivariable analysis, high peritoneal cancer index score and NACT were negatively associated to DFS and OS. Surgical complexity and CC-1 were negatively associated to DFS.Conclusion: PDS offered a survival gain of almost three years compared to IDS in patients with minimal or no residual disease after surgery. PDS should remain the standard of care for advanced ovarian cancer.

IntroductionRecent evidence has shown adverse oncological outcomes when minimally invasive surgery is used in early-stage cervical cancer. The objective of this study was to compare disease-free survival in patients that had undergone radical hysterectomy and pelvic lymphadenectomy, either by laparoscopy or laparotomy.MethodsWe performed a multicenter, retrospective cohort study of patients with cervical cancer stage IA1 with lymph-vascular invasion, IA2, and IB1 (FIGO 2009 classification), between January 1, 2006 to December 31, 2017, at seven cancer centers from six countries. We included squamous, adenocarcinoma, and adenosquamous histologies. We used an inverse probability of treatment weighting based on propensity score to construct a weighted cohort of women, including predictor variables selected a priori with the possibility of confounding the relationship between the surgical approach and survival. We estimated the HR for all-cause mortality after radical hysterectomy with weighted Cox proportional hazard models.ResultsA total of 1379 patients were included in the final analysis, with 681 (49.4%) operated by laparoscopy and 698 (50.6%) by laparotomy. There were no differences regarding the surgical approach in the rates of positive vaginal margins, deep stromal invasion, and lymphovascular space invasion. Median follow-up was 52.1 months (range, 0.8–201.2) in the laparoscopic group and 52.6 months (range, 0.4–166.6) in the laparotomy group. Women who underwent laparoscopic radical hysterectomy had a lower rate of disease-free survival compared with the laparotomy group (4-year rate, 88.7% vs 93.0%; HR for recurrence or death from cervical cancer 1.64; 95% CI 1.09–2.46; P=0.02). In sensitivity analyzes, after adjustment for adjuvant treatment, radical hysterectomy by laparoscopy compared with laparotomy was associated with increased hazards of recurrence or death from cervical cancer (HR 1.7; 95% CI 1.13 to 2.57; P=0.01) and death for any cause (HR 2.14; 95% CI 1.05–4.37; P=0.03).ConclusionIn this retrospective multicenter study, laparoscopy was associated with worse disease-free survival, compared to laparotomy.

Objective: To evaluate the oncological outcomes of patients with low-volume metastasis compared to those with macrometastasis and negative nodes in endometrial cancer. Methods: A single institutional retrospective study was carried out, which included all patients with endometrial cancer who underwent surgical treatment between January 2007 and December 2016. We analyzed the progression-free survival (PFS) and overall survival (OS) of all patients after sentinel node biopsy and full nodal surgical staging according to their final pathological nodal status, focusing on the impact of the size of nodal metastasis. Results: A total of 270 patients were operated on during the study period, among them, 230 (85.2%) patients underwent nodal staging. On final pathology, 196 (85.2%) patients had negative lymph nodes, low-volume metastasis (LVM) was present in 14 (6.1%) patients: 6 (2.6%) patients had isolated tumor cells (ITCs) and 8 (3.5%) patients presented just micrometastasis, additionally, 20 (8.7%) patients presented macrometastasis. After a median (range) follow-up of 60 (0&ndash, 146) months, patients with macrometastasis showed a significantly worse PFS compared to LVM and node-negative patients (61.1% vs. 71.4% vs. 83.2%, respectively, p = 0.018), and similar results were obtained for 5-year OS (50% vs. 78.6% vs. 81.5%, respectively, p &lt, 0.001). Half of the patients presenting LVM did not receive adjuvant treatment. Moreover, LVM had a moderate nonsignificant decrease in 5-year PFS compared to node-negative patients. Conclusions: Patients with endometrial cancer and low-volume nodal metastasis demonstrated a better prognosis than those presenting macrometastasis. Low-volume metastasis did not show worse oncological outcomes than node-negative patients, although there was a slight decrease in progression-free survival.

The aim of the present study was to compare the fasciolicidal efficacy in cattle of an experimental water-soluble compound, named fosfatriclaben, a prodrug of triclabendazole, with two commercial fasciolicides. For this, twenty-four cross mixed milking cows, aged between 1 to 3 years, naturally infected with Fasciola hepatica, were used. To apply the treatment, animals were divided into 4 groups of 6 animals each being ranked according to their fecal fluke-egg count from the highest to the lowest number of eggs. The compounds were administered in the groups with a single dose. Group 1 (G1) was treated with 6 mg/kg/IM of fosfatriclaben, G2 was treated with triclabendazole at 12 mg/kg/PO; G3 was treated with 5% closantel at 10 mg/kg/SC and G4 was administered with 5 mL/IM of deionized water and served as untreated control. Fecal samples were analyzed on days—8, 0 (treatment day), 7, 14, 21 and 28 to count the number of fasciola eggs before and after the treatment using the sedimentation test. The efficacy was assessed as the percentage of fluke-egg reduction on treated groups relative to the untreated control. The resulting data were analyzed by the Kruskal-Wallis non-parametric test, using the statistical IBM SPSS 24.0 (2016) program. Results indicated a fluke-egg reduction of 100% for fosfatriclaben along the study; triclabendazole showed an efficacy of 99.7% - 100% from day 7 to day 28. In the case of closantel, values from 98.8% to 99.6% were recorded from day 7 to day 28. No statistical differences between treatments were observed (P < 0.05). It was concluded that the experimental fosfatriclaben administered at 6 mg/kg/IM to naturally infected cattle exerted a fasciolicidal efficacy similar to the drugs of choice for the treatment of fasciolosis (triclabendazole) when administered at 12 mg/kg/ PO, and closantel injected at 10 mg/kg/SC.

The maintenance of a healthy skin barrier is crucial to prevent and treat atopic dermatitis (AD) lesions and avoid infections. Glycomacropeptide (GMP) is a bioactive peptide that has demonstrated promising results as an anti-inflammatory and antipruritic therapy for experimental AD. This study aimed to analyze the effect of GMP on impaired cutaneous barrier-related signs in a rat model of AD lesions. AD-like dermatitis was induced on the skin by repeated topical applications of 2,4-dinitrochlorobenzene, and animals were orally administered GMP before or after AD induction. The expression of skin structural proteins and antimicrobial peptides (AMPs) was evaluated by immunoblot or immunohistochemistry, epidermal thickening was evaluated by histochemistry, the level of IFN-γ and changes in the microbiota were evaluated by quantitative polymerase chain reaction, and the quantity of fecal short-chain fatty acids (SCFAs) was evaluated by gas chromatography. GMP administration significantly increased filaggrin, β-defensin 2, and cathelicidin-related AMP expression in AD-like lesions. Involucrin expression was not modified. In GMP-treated animals, epidermal thickening and IFN-γ expression were strongly reduced in damaged skin. GMP treatment impacted the skin microbiota and prevented Staphylococcus aureus colonization, which is associated with AD. In addition, high levels of Bifidobacterium were detected in the feces of GMP-treated animals, and the acetic acid and butyric acid contents increased in animals prophylactically administered GMP. These results suggest that GMP markedly prevents or reverses skin barrier damage in rat AD-like lesions through a bifidogenic effect that induces fecal SCFA production with prolonged treatment. Our findings provide evidence that GMP may represent an optimum strategy for the therapy of the dysfunctional cutaneous barrier in AD.

Background/aim Predicting response to treatment in high-grade serous ovarian carcinoma (HGSOC) still remains a clinical challenge. The standard-of-care for first-line chemotherapy, based on a combination of carboplatin and paclitaxel, achieves a high response rate. However, the development of drug resistance is one of the major limitations to efficacy. Therefore, identification of biomarkers able to predict response to chemotherapy in patients with HGSOC is a critical step for prognosis and treatment of the disease. Several studies suggest that angiogenesis is an important process in the development of ovarian carcinoma and chemoresistance. The aim of this study was to identify a profile of angiogenesis-related genes as a biomarker for response to first-line chemotherapy in HGSOC. Materials and methods Formalin-fixed paraffin-embedded samples from 39 patients with HGSOC who underwent surgical cytoreduction and received a first-line chemotherapy with carboplatin and paclitaxel were included in this study. Expression levels of 82 angiogenesis-related genes were measured by quantitative real-time polymerase chain reaction using TaqMan low-density arrays. Results Univariate analysis identified five genes [angiopoietin 1 (ANGPT1), aryl hydrocarbon receptor nuclear translocator (ARNT), CD34, epidermal growth factor (EGF) and matrix metallopeptidase 3 (MMP3)] as being statistically associated with response to treatment. Multivariable analysis by Lasso-penalized Cox regression generated a model with the combined expression of seven genes [angiotensinogen (AGT), CD34, EGF, erythropoietin receptor (EPOR), interleukin 8 (IL8), MMP3 and MMP7)]. The area under the receiver operating characteristics curve (0.679) and cross-validated Kaplan-Meier survival curves were used to estimate the accuracy of these predictors. Conclusion An angiogenesis-related gene expression profile useful for response prediction in HGSOC was identified, supporting the important role of angiogenesis in HGSOC.

Purpose: To analyze the influence of adding gentamicin to a regimen consisting of β-lactam or vancomycin plus rifampicin on survival in patients suffering from Staphylococcal prosthetic valve endocarditis (SPVE). Methods: From January 2008 to September 2016, 334 patients with definite SPVE were attended in the participating hospitals. Ninety-four patients (28.1%) received treatment based on β-lactam or vancomycin plus rifampicin and were included in the study. Variables were analyzed which related to patient survival during admission, including having received treatment with gentamicin. Results: Seventy-seven (81.9%) were treated with cloxacillin (or vancomycin) plus rifampicin plus gentamicin, and 17 patients (18.1%) received the same regimen without gentamicin. The causative microorganism was Staphylococcus aureus in 40 cases (42.6%) and coagulase-negative staphylococci in 54 cases (57.4%). Overall, 40 patients (42.6%) died during hospital admission, 33 patients (42.9%) in the group receiving gentamicin and 7 patients in the group that did not (41.2%, P = 0.899). Worsening renal function was observed in 42 patients (54.5%) who received gentamicin and in 9 patients (52.9%) who did not (p = 0.904). Heart failure as a complication of endocarditis (OR: 4.58; CI 95%: 1.84–11.42) and not performing surgery when indicated (OR: 2.68; CI 95%: 1.03–6.94) increased mortality. Gentamicin administration remained unrelated to mortality (OR: 1.001; CI 95%: 0.29–3.38) in the multivariable analysis. Conclusions: The addition of gentamicin to a regimen containing vancomycin or cloxacillin plus rifampicin in SPVE was not associated to better outcome.

Entamoeba histolytica is the causative agent of amoebiasis, which infects an estimated 50 million people globally each year. This parasite uses glycolysis as its only source of energy making enzymes of this route such as phosphoglycerate mutase (EhPGAM) excellent targets in the search for new drugs, a continuing necessity due to the adverse effects and unsuccessful cases of treatment that have resulted from the use of available antiparasitic agents. The aim of this work is to present the biochemical and structural characterization of EhPGAM and the results of a search for the first inhibitors of this enzyme. To this end, the activity of purified recombinant EhPGAM was assessed against an in-house chemical library of 200 benzimidazole derivatives. The results showed that seven compounds inhibited this enzyme about 40–70% at 100 μM and molecular dynamics simulations indicated that the two most potent inhibitors (Compound 1 and Compound 2) form stable complexes and have the highest binding energy. Hence, these inhibitors can be considered good candidates in the search of new drugs to treat amoebiasis.

Background: Recent reports have identified distinct genomic patterns in ovarian carcinoma, including proliferative and mesenchymal-like groups, with worse outcome. The exact mechanisms driving the onset and progression of these tumors are still poorly understood. Additionally, researchers are concerned about the correct subtype stratification of the available cell line models, and the exploration of alternatives to monolayer culture. Identification of biomarkers to stratify cell lines, characterization of important processes as epithelial-mesenchymal transition (EMT), and the use of three-dimensional (3D) cultures as alternative models could be useful for cell line classification. Methods and Results: In this work, we present a descriptive analysis of 16 commonly used ovarian cancer cell lines. We have studied their morphology in 2- and 3D culture, and their response to cisplatin, observing in the majority of them an increased resistance in 3D. We have also performed an immunohistochemical analysis for proliferation marker Ki-67, and EMT related markers to establish phenotypes. Epithelial cells tend to show higher proliferative rates, and mesenchymal cells show an increase in EMT related markers, especially when cultured in 3D conditions. Conclusions: We have stated the complex heterogeneity of ovarian cancer models, resembling primary tumors, agreeing with the argument that the cell line model for in vitro experiments must be carefully chosen. Our results also support that tridimensional culture could be a very helpful alternative in ovarian cancer research. Regarding EMT, a very important process for the development of this disease, some related biomarkers might be further characterized for their role in this disease development, This work was funded by Instituto de Salud Carlos III (ISCIII) and Fondo Europeo de Desarrollo Regional (FEDER), as part of PN I+D+I 2008–2011 Program (#PI10/630) and Fundación Mutua Madrileña Funding Program. VHS was supported by a phD fellowship program (#FI11/00538, ISCIII) and CIBERONC CB16/12/00398

Objectives To analyze the pregnancy, live birth, and miscarriage rates of the IVF/ICSI cycles in women with low levels of AMH, compared to patients with normal levels of this hormone. Methods We carried out an observational and retrospective study with the data of the patients treated in 2017 and 2018 in the Assisted Reproduction Section of La Paz University Hospital (LPHU), comparing 223 low responder patients (AMH Results Pregnancy rate was lower in the AMH Conclusion Patients with low ovarian reserve have a lower pregnancy rate compared to patients with a normal ovarian reserve. AMH plays a key role as an ovarian response marker in IVF cycles, although age is one of the factors that should be considered.

Objective Ileocecal endometriosis is rare. Symptoms range from no symptoms, cramps, vomiting, to acute intestinal obstruction. Our objective was to review our cases, clarify, and resume its most appropriate management focusing on the factors to determine diagnosis. This is a retrospective study by revision of medical charts of all ileal endometriosis cases of our unit from 2006 to 2014. Case Report Seven cases were found; three (43%) had previous endometriosis laparoscopic diagnosis, four (57%) had partial bowel obstruction episodes, three (43%) had chronic pelvic pain, and one developed acute intestinal obstruction in postoperative ileostomy closure. In three (43%), the diagnosis was made with magnetic resonance imaging (MRI) and double contrast barium enema, in one (14%) only with MRI, and the other three (43%) during surgery. All patients underwent resection of the ileum and evolved favorably. Conclusion Variability in symptoms hinders diagnosis. The gold standard for diagnosis is MRI, but clinical suspicion optimizes imaging test diagnosis. Segmental resection should be indicated in the majority of the cases.

GAMES Investigators., [Background] Enterococcal endocarditis (EE) is a growing entity in Western countries. However, quality data from large studies is lacking., [Objectives] The purpose of this study was to describe the characteristics and analyze the prognostic factors of EE in the GAMES cohort., [Methods] This was a post hoc analysis of a prospectively collected cohort of patients from 35 Spanish centers from 2008 to 2016. Characteristics and outcomes of 516 cases of EE were compared with those of 3,308 cases of nonenterococcal endocarditis (NEE). Logistic regression and Cox proportional hazards regression analysis were performed to investigate risk factors for in-hospital and 1-year mortality, as well as relapses., [Results] Patients with EE were significantly older; more frequently presented chronic lung disease, chronic heart failure, prior endocarditis, and degenerative valve disease; and had higher median age-adjusted Charlson score. EE more frequently involved the aortic valve and prosthesis (64.3% vs. 46.7%; p < 0.001; and 35.9% vs. 28.9%; p = 0.002, respectively) but less frequently pacemakers/defibrillators (1.5% vs. 10.5%; p < 0.001), and showed higher rates of acute heart failure (45% vs. 38.3%; p = 0.005). Cardiac surgery was less frequently performed in EE (40.7% vs. 45.9%; p = 0.024). No differences in in-hospital and 1-year mortality were found, whereas relapses were significantly higher in EE (3.5% vs. 1.7%; p = 0.035). Increasing Charlson score, LogEuroSCORE, acute heart failure, septic shock, and paravalvular complications were risk factors for mortality, whereas prior endocarditis was protective and persistent bacteremia constituted the sole risk factor for relapse., [Conclusions] Besides other baseline and clinical differences, EE more frequently affects prosthetic valves and less frequently pacemakers/defibrillators. EE presents higher rates of relapse than NEE.

Purpose To assess the impact of laparoscopic extraperitoneal paraaortic staging in therapeutic planning and prognosis of patients with locally advanced cervical cancer (LACC) as compared with imaging staging. Methods Retrospective multicenter study of stage IB2 and IIA2 to IVA (FIGO 2009) LACC patients who were candidates for primary chemoradiotherapy. The study (surgical) group included 634 patients undergoing laparoscopic/robotic extraperitoneal paraaortic staging treated with extended-field radiotherapy (EFRT) if lymph node involvement was confirmed. The control (imaging) group included 288 patients treated with EFRT when lymph node involvement was suspected on positron emission tomography-computed tomography scans and/or magnetic resonance imaging. Results In the study group, a median of 13 (range 9-17) lymph nodes were removed, with a rate of positive paraaortic nodes of 18%, with metastatic size

To analyze the current management and use of fertility preservation (FP) treatments among different gynecologic oncology centers in Spain METHODS: From March to April 2019, a transversal study was conducted using a national online survey to consultants registered in the section of Gynecologic Oncology of the Spanish Society of Obstetrics and Gynecology. The survey contained 30 questions that assessed the perceptions and attitudes towards fertility-sparing strategies as well as its management in each participating center.A total of 51 responders from 12 out of 17 geographical regions of Spain answered the survey. According to 35 responders (68.63%), the age limit for offering FP was 40 years. In most of the centers, an ovarian reserve study is carried out prior to a FP procedure (34 responders, 66.67%). In cervical cancer size, limit for offering trachelectomy is 2 cm (40 responders, 78.43%), with LVSI as an exclusion factor for 26 (51%). Twenty-four (48.98%) responders reported that FP only in ovarian cancer stages IA, 12 (24.49%) also in stages IB, and an additional 13 (26.53%) up to stages IC. Most responders perform FP only in the absence of myometrial infiltration (30, 58.82%) in patients with g1-g2 endometrial cancer.The performance of professionals at the national level is uneven, demonstrating the need for referral centers to ensure optimal management. International guidelines should be more widely extended throughout Spain to homogenize the treatment of young oncology patients who wish to have children.

Objective: To investigate the rate of colorectal neoplasms (CRNs) in patients who have Enterococcus faecalis infective endocarditis (EFIE) with available colonoscopies and to assess whether this is associated with the identification of a focus the infection. Patients and Methods: Retrospective analysis of data from a prospective multicenter study involving 35 centers who are members of the Grupo de Apoyo para el Manejo de la Endocarditis en Espana [Support Group for the Management of Infective Endocarditis in Spain] cohort. A specific set of queries regarding information on colonoscopy and histopathology of colorectal diseases was sent to each participating center. Four-hundred sixty-seven patients with EFIE were included from January 1, 2008, to December 31, 2017, from whom data on colonoscopy performance and results were available in 411 patients. Results: One hundred forty-two (34.5%) patients had a colonoscopy close to the EFIE episode. The overall rate of colorectal diseases was 70.4% (100 of 142), whereas the prevalence of CRN (advanced adenomas and colorectal carcinoma) was 14.8% (21 of 142), with no significant differences between the group of EFIE of unknown focus and that with an identified focus. Conclusion: Our study adds to prior evidence suggesting a much higher rate of CRN among patients with EFIE than in the general population of the same age and sex. In addition, our findings suggest that this phenomenon might take place both in EFIE with an unknown and an identified source of infection.

Introduction/Background The development of the extraperitoneal space uses to be the most challenging step to perform an extraperitoneal para-aortic lymphadenectomy. Few papers describe the technique, but none explain step by step how to develop this virtual space effectively. The success on developing it will influence the rest of the surgical procedure. Methodology In the video a step by step technique is carefully explained, adding tips a tricks on haw to avoid peritoneal rupture of development of wrong spaces that may difficult the dissection. Additionally graphs and pictures have been added to the video to illustrate the technique. Results The crucial steps include diagnostic: laparoscopy to assess spread of the disease, development of the extraperitoneal layer under direct vision, first trocar placement and insulation of the extrapneumoperitoneum, accessory tracers placement and dissection of the para-aortic space. Conclusion A systematic technique can improve the success rate of exztraperitoneal para-aortic lymphadenectomy. Disclosure Nothing to disclose

Introduction/Background Despite the use of nerve-sparing technique, bladder dysfunction remains the leading morbidity associated with parametrectomy (radical hysterectomy or trachelectomy). Our aim was to analyze the time to postoperative voiding recovery and the factors influencing it in the SENTIX trial cohort, in whom different types of surgical approach and parametrectomy was used. Methodology The SENTIX trial is a prospective cohort international study on sentinel lymph node biopsy without pelvic lymphadenectomy in patients with early-stage cervical cancer (≤4 cm or ≤2cm in fertility sparing). It entails 46 sites from 18 countries. Ad hoc analysis of data from the SENTIX trial was performed to assess factors influencing voiding recovery, which was defined as the number of days from surgery to bladder catheter or epicystostomy removal with post-voiding urine residuum Result The characteristics of the cohort of 372 patients are shown in table 1. Median (range) voiding recovery time was 3 (0–21) days; it was 1 month, only 1 case (80 days) was not associated with any severe intraoperative complication (6 cases) or adjuvant radiotherapy (3 cases). Tumor size >2 cm, open surgery, and a more extensive type of parametrectomy significantly influenced voiding recovery (figure 1). In multivariate analysis, only previous pregnancy and type of parametrectomy were significant (table 2). Conclusion Voiding recovery time is directly related to the extent of parametrectomy. It is, however, temporary and almost all patients recover within 1 month, even after a more radical procedure (C2). The higher risk associated with laparotomy reflects a tendency to be more radical with open surgery. Disclosure This work was supported by a grant from the Czech Research Council (No 16-31643A). There are no conflicts of interest.

Low-grade and early Federation for Gynecology and Obstetrics (FIGO) stage endometrioid endometrial carcinomas (EEC) have an excellent prognosis. However, approximately 10% of patients develop recurrence, which cannot be correctly predicted at diagnosis. We evaluated myoinvasive patterns as a prognostic factor of relapse in low-grade, early-stage EEC. Two-hundred and fifty-eight cases were selected according to the following inclusion criteria: (i) endometrioid endometrial carcinomas, (ii) grade 1 or 2 with (iii) FIGO stage I or II, and (iv) clinical follow-up. Slides were reviewed to annotate the myoinvasive pattern present in each case (infiltrative glands, microcystic, elongated and fragmented –MELF-, broad front, adenomyosis-like and adenoma malignum). Microsatellite instability was studied by immunoexpression of mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6). There were 29 recurrences (11.2%) among the 258 cases analysed. A predominant broad front myoinvasive pattern was significantly associated with tumour relapse (p = 0.003). The presence of a pattern of infiltrative glands (p = 0.001) and microsatellite instability (p = 0.004) were associated with lower disease-free survival, without having an impact on overall survival. Our observations suggest the potential value of the pattern of myoinvasion as a prognostic factor in low-grade, early-stage endometrioid endometrial carcinoma, This research was funded by the Instituto de Salud Carlos III (ISCIII) (PI17/01723), co-financed by the European Development Regional Fund ‘A way to achieve Europe’ (FEDER).

e17549 Background: In contrast to high-grade serous ovarian cancer, relationship between tumor infiltrating lymphocytes (TILs) with endometrioid (EC) and clear cell ovarian carcinomas (CC) are less known. However, these tumors are thought to arise from a transformed endometriosis, a disease with a marked inflammatory response, and are also more related to Lynch syndrome. The characterization of TILs in these tumors could lead to stratify patients according to their prognosis and to identify candidates for immumotherapy in case of relapse. Methods: We conducted a retrospective observational study of 121 patients with EC and CC, diagnosed and treated in La Paz University Hospital, from November 1992 until December 2013. An expert pathologist reviewed the histopathological diagnosis, using the immunohistochemical algorithm with WT1, p53, Napsin A and progesterone receptor, and the presence of endometriosis. Clinicopathological data, genetic testing and personal and familial background were collected. Tissue-microarrays (TMAs) were used to analyze CD8+, CD4+ and CD3+ intra-epithelial TILs, according to the score designed by the Ovarian Tumor Tissue Analysis Consortium, peritumoral and endometriosis lymphocytes, ARID1A, MLH1, PMS2, MSH2 and MSH6. Software SPSS18 version was used for descriptive and statistical analysis. Results: Mean age was 54.3 years, and the median follow-up 10.02 years. 48.8% were CC and 51.2% EC, of which, 55.9% were well-differentiated, 32.2% moderately and 11.9% poorly. 58.8% of patients were diagnosed in early stages and 41.2% in advanced ones. 9.1% had family history of ovarian, colorectal or endometrial cancer and 16.5% of breast cancer. 37.2% of patients had a relapse (median progression-free survival of 31 months) and 41.6% died (32.6% related to the tumor). 55.4% of the patients had endometriosis (53.2% were EC and 57.6% CC). 8.2% had lost of MLH1, PMS2, MSH2 or MSH6 and 42% lost ARID1A expression. Moderate or high levels of CD3+, CD8+ and CD4+ TILs were seen in the 57.9%, 53.7% and 1.1%, respectively. There was no relationship between TILs and the lost of MLH1, PMS2, MSH2 and MSH6. Moderate or higher levels of CD3+ TILs were related with better overall survival (OS) only in early stages (p = 0.045). Increased CD8+ TILs in EC patients were associated with a trend towards an improved OS in comparison with those patients with lower or negative CD8+ TILs. Moderate o higher levels of CD8+ TILs were also associated, without statistical significance, with the presence of endometriosis and ARID1A. Conclusions: In our study CD3+ TILs correlated to a better OS, but only in early stages of CC and EC. CD8+ TILs were also associated with a tendency to better OS in EC. We did not find statistically significant association between TILs and Mismatch Repair System deficiency, ARID1A or endometriosis.

Limited data are available on direct-acting antivirals for treating hepatitis C virus (HCV) infection in patients with severe renal impairment. The aim of this study was to evaluate the effectiveness and safety of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) ± dasabuvir (DSV) ± ribavirin (RBV) in patients with stage 4 or 5 chronic kidney disease (CKD) and HCV genotype 1 or 4 infection in real clinical practice, and to investigate pharmacological interactions. This retrospective study included patients treated with OBV/PTV/r+DSV±RBV or OBV/PTV/r+RBV with CKD stage 4 (eGFR: 15-29 mL/min/1.73m2 ) or 5 (eGFR

Objective: This article shows our experience on sentinel lymph node (SLN) biopsy in early-stage cervical carcinoma since the technique was introduced in our Institution. The main objective is to analyze the detection rate (DR) of metastatic SLNs, identifying prognostic factors for an increased risk of nodal metastases. Our second aim was to compare the accuracy of nodal metastases DR between intraoperative analysis and postoperative ultrastaging. Materials and Methods: Forty-one women with the International Federation of Gynecology and Obstetrics stages IA2-IIA1 who underwent laparoscopic surgical treatment applying the SLN technique, from December 2011 to June 2016, at La Paz University Hospital, were included. The sentinel node was identified using technetium and methylene blue dye or indocyanine green near-infrared fluorescent imaging, analyzed intraoperatively, and compared to deferred ultrastaging. Results: SLN DR was 100%, with a bilaterality rate of 83%. Twelve (26.8%) patients had metastatic nodes, 11 of them (91.7%) detected by SLN technique, of which 9 (81.8%) had only the sentinel node affected. False-negative rate was 2.4% after ultrastaging procedure. Metastatic SLN detection with ultrastaging was 45.5% higher than the intraoperative analysis, 63.6% of which had low tumor burden. The global detection of patients with nodal metastases after SLN technique was 21.9% higher than pelvic lymphadenectomy. Conclusions: Our preliminary results corroborate that SLN biopsy selectively maps metastatic nodes and ultrastaging increases the detection of metastatic SLNs, predominantly due to low tumor burden.

Introduction Endometriosis affecting the sciatic nerve is extremely uncommon. Its main symptom is catamenial sciatica but it can result in neuropathy. The diagnosis is usually delayed for years. Our objective is to communicate our experience in the diagnosis, management and treatment of this pathology by presenting two patients. Methods Retrospective revision of medical charts of all sciatic endometriosis cases treated in the Endometriosis Unit of the University Hospital, La Paz, Spain. Results Two nulliparous patients 35 and 39 years old, with unilateral sciatica related to sciatic nerve endometriosis are presented. The lag time between the onset of symptoms and diagnosis was 8 and 5 years. Both patients had problems with locomotion and muscle atrophy, so laparoscopic neurolysis was performed with success in pain control but not total recovery of deambulation defect. Conclusions Directed anamnesis and magnetic resonance imaging (MRI) are good tools for diagnosis of endometriosis affecting sciatic nerve. In absence of neuropathy, hormonal pharmacotherapy can be used to control symptoms, but when it is present, surgical nerve decompression must not be delayed, and laparoscopic approach is feasible for trained surgeons. In our cases, neurolysis improved pain but complete recovery of motor function has not been reached. Physicians responsible for primary care need to be aware of the catamenial sciatica due to the nerve damage caused by endometriosis, even when it is very uncommon, because the consequences of the delay in assessment and treatment by a specialized multidisciplinary team in dedicated units may be irreversible.

Background Candida auris is an emerging multidrug-resistant yeast that can cause invasive infections and is associated with high mortality. It is typically resistant to fluconazole and voriconazole and, some cases, also to echinocandins and amphotericin B. This species, phylogenetically related to Candida haemulonii, is frequently misidentified by commercial identification techniques in clinical laboratories; therefore, the real prevalence of C. auris infections may be underestimated. Aims To describe the clinical and microbiological features of the first four cases of C. auris fungemia episodes observed in the European continent. Methods The four patients were hospitalized in the adult surgical intensive care unit. A total of 8 isolates (two per patient) from blood and catheter tip were analyzed. Results All isolates were misidentified as Saccharomyces cerevisiae by AuxaColor 2, and as Candida sake by API ID20C. VITEK MS technology misidentified one isolate as Candida lusitaniae, another as C. haemulonii and could not identify the other six. C. auris identification was confirmed by ITS rDNA sequencing. All isolates were fluconazole (MIC >256 mg/l) and voriconazole (MIC 2 mg/l) resistant and susceptible to posaconazole, itraconazole, echinocandins and amphotericin B. Conclusions C. auris should be regarded as an emerging pathogen, which requires molecular methods for definitive identification. Our isolates were highly resistant to fluconazole and resistant to voriconazole, but susceptible to the other antifungals tested, which emphasizes the importance of accurately identifying this species to avoid therapeutic failures.

Aim To validate the Spanish version of the Uterine Fibroid Symptom and Quality of Life (UFS-QoL)questionnaire in women with uterine myomatosis, in order to assess severity of symptoms, and their impact on health-related quality of life. Materials and methods The participants were recruited in gynaecology clinics. The UFS-QoL questionnaire comprises 37 items, 8 of which assess severity of symptoms, and the remaining 29 assess health-related quality of life in 6 subscales. Internal consistency, concurrent and discriminant validity, test-retest reliability, and the scale’s sensitivity to change were evaluated. Results A total of 619 patients with uterine myomatosis, and 57 women without myomatosis, took part in the study. Cronbach’s alpha was 0.97, and the test-retest reliability was 0.90 for the overall scale. TheUFS-QoL not only discriminated between patients and healthy controls but also between patients with different degrees of uterine myomatosis. The scale responded to changes after treatment with an effect size of 1.2. Conclusions The Spanish version of the UFs-QoL questionnaire, used in a sample of the Spanish population, proved a valid and reliable tool to differentiate patients with uterine myomatosis and different grades of symptoms, and to evaluate the impact of the severity of these symptoms on health-related quality of life. In addition, the UFs-QoL proved sensitive to the changes generated by myomatosis treatment.

Introduction Mexico is the country with the highest mortality due to acute myocardial infarction in adults older than 45 years old according to the OECD (28 vs. 7.5% of the average). The first real-world study, RENASCA IMSS, showed a high-risk population at 65%, but 50% without reperfusion strategies. The aim was to describe the clinical presentation, treatment, and outcomes of acute coronary syndromes at the IMSS. Methods RENASCA IMSS is a nation-wide, prospective, longitudinal-cohort study. We include consecutive patients with an Acute Coronary Syndrome diagnosis (ACC/AHA/ESC) admitted in 177 representative hospitals of the IMSS (166 of second level and 11 of third level of attention). In an electronic database clinical, paraclinical, times, reperfusion treatment, complications, and other variables were assessed. Confidentiality was maintained in data and informed consent was obtained. Registrer calibration was performed with more than 80% of the variables and 80% of the cases. Results From March 1, 2014 to December 25, 2017; 21,827 patients were enrolled presenting an average age 63.2 ± 11.7, 75% men (16,259) and 25% women (5,568). The most frequent risk factors were: hypertension (60.5%), smoking (46.8%), diabetes (45.5%), dyslipidemia (35.3%) and metabolic syndrome (39.1%). STEMI diagnosis was established in 73.2% of the patients and NSTEMI in 26.8%. The STEMI group within the Code Infarction showed an improvement in the reperfusion therapy (34.9% before vs. 71.4% after, p ≤0.0001) and reduction of mortality (21.1 vs. 9.4%, p ≤0.0001); while the NSTEMI group showed high risk set by a GRACE score of 131.5 ± 43.7 vs. 135.9 + 41.7, p ≤0.0001. Mortality was more frequent within the STEMI group (14.9 vs. 7.6%, p ≤0.0001). Conclusions RENASCA IMSS study represents the largest Acute Coronary Syndromes real-world study in Mexico, demonstrating that the Mexican population has a high risk. Patients with a STEMI diagnosis were more frequently enrolled and were associated with higher mortality and complications; however, there is improvement in the reperfusion therapy and in mortality with the Code Infarction strategy.