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This paper addresses the challenge of embedded computing resources required by future autonomous Unmanned Aircraft Systems (UAS). Based on an analysis of the required onboard functions that will lead to higher levels of autonomy, we look at most common UAS tasks to first propose a classification of UAS tasks considering categories such as flight, navigation, safety, mission and executing entities such as human, offline machine, embedded system. We then analyse how a given combination of tasks can lead to higher levels of autonomy by defining an autonomy level. We link UAS applications, the tasks required by those applications, the autonomy level and the implications on computing resources to achieve that autonomy level. We provide insights on how to define a given autonomy level for a given application based on a number of tasks. Our study relies on the state-of-the-art hardware and software implementations of the most common tasks currently used by UAS, also expected tasks according to the nature of their future missions. We conclude that current computing architectures are unlikely to meet the autonomy requirements of future UAS. Our proposed approach is based on dynamically reconfigurable hardware that offers benefits in computational performance and energy usage. We believe that UAS designers must now consider the embedded system as a masterpiece of the system.
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AIMS: Immunotherapy is a rising alternative to traditional treatment in breast cancer (BC) patients in order to transform cold into hot immune enriched tumours and improve responses and outcome. A computational modelling approach was applied to quantify modulation effects of immunotherapy and chemotherapy response on tumour shrinkage and progression-free survival (PFS) in naïve BC patients. METHODS: Eighty-three Her2-negative BC patients were recruited for neoadjuvant chemotherapy with or without immunotherapy based on dendritic cell vaccination. Sequential tumour size measurements were modelled using nonlinear mixed effects modelling and linked to PFS. Data from another set of patients (n = 111) were used to validate the model. RESULTS: Tumour size profiles over time were linked to biomarker dynamics and PFS. The immunotherapy effect was related to tumour shrinkage (P < .05), with the shrinkage 17% (95% confidence interval: 2-23%) being higher in vaccinated patients, confirmed by the finding that pathological complete response rates in the breast were higher in the vaccinated compared to the control group (25.6% vs 13.6%; P = .04). The whole tumour shrinkage time profile was the major prognostic factor associated to PFS (P < .05), and therefore, immunotherapy influences indirectly on PFS, showing a trend in decreasing the probability of progression with increased vaccine effects. Tumour subtype was also associated with PFS (P < .05), showing that luminal A BC patients have better prognosis. CONCLUSIONS: Dendritic cell-based immunotherapy is effective in decreasing tumour size. The semi-mechanistic validated model presented allows the quantification of the immunotherapy treatment effects on tumour shrinkage and establishes the relationship between the dynamics of tumour size and PFS.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/terapia , Vacunas contra el Cáncer/administración & dosificación , Células Dendríticas/inmunología , Modelos Biológicos , Terapia Neoadyuvante/métodos , Adulto , Anciano , Anciano de 80 o más Años , Mama/inmunología , Mama/patología , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Vacunas contra el Cáncer/inmunología , Estudios de Casos y Controles , Quimioterapia Adyuvante , Estudios de Cohortes , Simulación por Computador , Femenino , Humanos , Mastectomía , Persona de Mediana Edad , Supervivencia sin Progresión , Carga Tumoral/inmunologíaAsunto(s)
Anticuerpos Monoclonales Humanizados/efectos adversos , Antineoplásicos Inmunológicos/efectos adversos , Miocarditis/etiología , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Enfermedad Aguda , Anciano , Anticuerpos Monoclonales Humanizados/administración & dosificación , Antineoplásicos Inmunológicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Autoinmunidad , Resultado Fatal , Femenino , Humanos , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Linfocitos Infiltrantes de Tumor/patología , Mieloma Múltiple/complicaciones , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/tratamiento farmacológico , Miocarditis/diagnóstico , Miocarditis/metabolismo , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Subgrupos de Linfocitos T/patologíaRESUMEN
BACKGROUND: Blood eosinophil count (BEC) is currently used as a surrogate marker of T2 inflammation in severe asthma but its relationship with tissue T2-related changes is elusive. Bronchial biopsy could add reliable information but lacks standardization. OBJECTIVES: To validate a systematic assessment of the bronchial biopsy for the evaluation of severe uncontrolled asthma (SUA) by standardizing a pathological score. METHODS: A systematic assessment of submucosal inflammation, tissue eosinophilic count/field (TEC), goblet cells hyperplasia, epithelial changes, basement membrane thickening, prominent airway smooth muscle and submucosal mucous glands was initially agreed and validated in representative bronchial biopsies of 12 patients with SUA by 8 independent pathologists. In a second phase, 62 patients with SUA who were divided according to BEC≥300cells/mm3 or less underwent bronchoscopy with bronchial biopsies and the correlations between the pathological findings and the clinical characteristics were investigated. RESULTS: The score yielded good agreement among pathologists regarding submucosal eosinophilia, TEC, goblet cells hyperplasia and mucosal glands (ICC=0.85, 0.81, 0.85 and 0.87 respectively). There was a statistically significant correlation between BEC and TEC (r=0.393, p=0.005) that disappeared after correction by oral corticosteroids (OCS) use (r=0.170, p=0.307). However, there was statistically significant correlation between FeNO and TEC (r=0.481, p=0.006) that was maintained after correction to OCS use (r=0.419, p=0.021). 82.4% of low-BEC had submucosal eosinophilia, 50% of them moderate to severe. CONCLUSION: A standardized assessment of endobronchial biopsy is feasible and could be useful for a better phenotyping of SUA especially in those receiving OCS.
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Asma , Eosinofilia , Humanos , Eosinófilos , Bronquios , Hiperplasia/patología , Asma/diagnóstico , Asma/tratamiento farmacológico , Asma/patología , Inflamación , BiopsiaRESUMEN
COVID-19 infection has been associated, particularly in severely ill patients requiring hospitalization, with a hypercoagulable state. The case presented herein was a 66-year-old man with SARS-CoV-2 infection who did not have any respiratory symptoms. He presented with the following clinical manifestations: portal vein and hepatic artery thrombosis, liver infarction, and a superimposed abscess of the liver. In this case, early detection and the administration of anticoagulants and antibiotics led to a significant improvement within weeks of the diagnosis. We encourage physicians to be aware of COVID-19-associated hypercoagulable state and its potential complications, regardless of the acuity of the presentation or the absence of respiratory symptoms.
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COVID-19 , Infarto Hepático , Absceso Hepático , Masculino , Humanos , Anciano , COVID-19/complicaciones , SARS-CoV-2 , Absceso Hepático/etiologíaRESUMEN
BACKGROUND: Primary breast cancer (BC) has shown a higher immune infiltration than the metastatic disease, justifying the optimal scenario for immunotherapy. Recently, neoadjuvant chemotherapy (NAC) combined with immune checkpoint inhibitors has demonstrated a gain in pathological complete responses (tpCR) in patients with BC. The aim of our study is to evaluate the safety, feasibility, and efficacy of the addition of dendritic cell vaccines (DCV) to NAC in HER2-negative BC patients. METHODS: Thirty-nine patients with early BC received DCV together with NAC conforming the vaccinated group (VG) and compared with 44 patients as the control group (CG). All patients received anthracyclines and taxanes-based NAC (ddECx4âDx4) followed by surgery ± radiotherapy ± hormonotherapy. RESULTS: The tpCR rate was 28.9% in the VG and 9.09% in the CG (p = 0.03). Pathological CR in the triple negative (TN) BC were 50.0% versus 30.7% (p = 0.25), 16.6% versus 0% in luminal B (p = 0.15), and none among luminal A patients in VG versus CG, respectively. Impact of DCV was significantly higher in the programmed cell death ligand 1 (PD-L1) negative population (p < 0.001). PD-L1 expression was increased in patients with residual disease in the VG as compared with the CG (p < 0.01). No grade ⩾3 vaccine-related adverse events occurred. With a median follow-up of 8 years, no changes were seen in event-free survival or overall survival. Phenotypic changes post DCV in peripheral blood were observed in myeloid-derived suppressor cells (MDSC), NK, and T cells. Increase in blood cell proliferation and interferon (IFN)-γ production was detected in 69% and 74% in the VG, respectively. Humoral response was also found. Clonality changes in TCR-ß repertoire were detected in 67% of the patients with a drop in diversity index after treatment. CONCLUSION: The combination of DCV plus NAC is safe and increases tpCR, with a significant benefit among PD-L1-negative tumors. DCV modify tumor milieu and perform cellular and humoral responses in peripheral blood with no impact in outcome. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT01431196. EudraCT 2009-017402-36.
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BACKGROUND: Difficult peripheral intravenous cannulation (DPIVC) is associated with serious complications related to vascular access. These complications might be avoided if the risk factors were identified previously, enabling the detection of potentially difficult situations at an early stage. The aim of this study is to consider these risk factors, to determine the influence of the hospital setting, to examine the association between DPIVC and the different techniques of catheter insertion and to analyse the importance of the clinician's experience in this context. METHODS: Case-control study following a previously published protocol, conducted in 48 units of eight public hospitals in Spain. Adult patients requiring a peripheral intravenous cannula were prospectively included in the study population during their hospital stay. Over a period of 11 months, for consecutive eligible patients, nurses in each participating unit recorded data on their assessment of the vascular access performed and the technique used. Variables related to these medical personnel were also recorded. One of the researchers reviewed the patients' clinical history to compile the relevant health variables and to characterise the healthcare process. The statistical analysis included association tests among the main study variables. The risk factors were analysed using bivariate logistic regression. The variables found to be statistically significant were included in a multivariate logistic regression model incorporating each of the healthcare environments identified. RESULTS: The study population was composed of 2662 patients, of whom 221 (8.3%) presented with DPIVC. A previous history of difficulty, the presence of non-palpable veins, acute upper limb alterations and punctures in the ante-cubital fossa were found to be independent risk factors for DPIVC. Differences were found in the frequency of occurrence of DPIVC and in some risk factors, according to the healthcare context. The variables related to the characteristics of the hospital personnel did not influence the study event. CONCLUSION: The present study identifies four independent risk factors for DPIVC that can be incorporated into algorithms aimed at preventing its occurrence and facilitating the referral of patients to vascular access specialist teams.
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PURPOSE: To determine the tumor tissue/cell distribution, functional associations, and clinical significance of PD-1, LAG-3, and TIM-3 protein expression in human non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Using multiplexed quantitative immunofluorescence, we performed localized measurements of CD3, PD-1, LAG-3, and TIM-3 protein in >800 clinically annotated NSCLCs from three independent cohorts represented in tissue microarrays. Associations between the marker's expression and major genomic alterations were studied in The Cancer Genome Atlas NSCLC dataset. Using mass cytometry (CyTOF) analysis of leukocytes collected from 20 resected NSCLCs, we determined the levels, coexpression, and functional profile of PD-1, LAG-3, and TIM-3 expressing immune cells. Finally, we measured the markers in baseline samples from 90 patients with advanced NSCLC treated with PD-1 axis blockers and known response to treatment. RESULTS: PD-1, LAG-3, and TIM-3 were detected in tumor-infiltrating lymphocytes (TIL) from 55%, 41.5%, and 25.3% of NSCLC cases, respectively. These markers showed a prominent association with each other and limited association with major clinicopathologic variables and survival in patients not receiving immunotherapy. Expression of the markers was lower in EGFR-mutated adenocarcinomas and displayed limited association with tumor mutational burden. In single-cell CyTOF analysis, PD-1 and LAG-3 were predominantly localized on T-cell subsets/NKT cells, whereas TIM-3 expression was higher in NK cells and macrophages. Coexpression of PD-1, LAG-3, and TIM-3 was associated with prominent T-cell activation (CD69/CD137), effector function (Granzyme-B), and proliferation (Ki-67), but also with elevated levels of proapoptotic markers (FAS/BIM). LAG-3 and TIM-3 were present in TIL subsets lacking PD-1 expression and showed a distinct functional profile. In baseline samples from 90 patients with advanced NSCLC treated with PD-1 axis blockers, elevated LAG-3 was significantly associated with shorter progression-free survival. CONCLUSIONS: PD-1, LAG-3, and TIM-3 have distinct tissue/cell distribution, functional implications, and genomic correlates in human NSCLC. Expression of these immune inhibitory receptors in TILs is associated with prominent activation, but also with a proapoptotic T-cell phenotype. Elevated LAG-3 expression is associated with insensitivity to PD-1 axis blockade, suggesting independence of these immune evasion pathways.
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Antígenos CD/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Receptor 2 Celular del Virus de la Hepatitis A/metabolismo , Neoplasias Pulmonares/patología , Linfocitos Infiltrantes de Tumor/inmunología , Receptor de Muerte Celular Programada 1/metabolismo , Análisis de la Célula Individual/métodos , Biomarcadores de Tumor/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/metabolismo , Activación de Linfocitos/inmunología , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Proteína del Gen 3 de Activación de LinfocitosRESUMEN
CONTEXT: - The rapid advances in targeted therapies in non-small cell lung cancer (NSCLC) make the optimization and implementation of cytology specimens for molecular testing a priority. Up to 70% of patients with NSCLC are diagnosed at advanced stages and tissue biopsies often cannot be taken. Although cytology samples provide high-quality material for molecular testing, molecular cytopathology is not yet well known or widely used. OBJECTIVE: - To report the many advances in molecular cytopathology and the suitability and utility of cytology samples in molecular and genetic testing of NSCLC. DATA SOURCES: - Data sources comprised published peer-reviewed literature and personal experience of the authors. CONCLUSIONS: - Molecular testing can be performed on cytologic specimens, especially on direct smears. Rapid on-site evaluation by cytopathologists has improved the adequacy and the management of cytology samples for molecular testing. Mutational profiling of NSCLC using next-generation sequencing can be performed on cytology samples from very small amounts of DNA. Fluorescence in situ hybridization assays on cytology specimens, including stained direct smear, offer some distinct advantages over their histologic counterpart, and are used to detect ALK and ROS1 rearrangements in NSCLC. Cytology specimens allow assessment of the entire tumor cell nucleus, avoiding signal loss from truncation artifacts. The use of cytology samples for assessing programmed death ligand-1 protein expression is currently being developed. Protocols for bisulfite conversion and DNA droplet digital polymerase chain reaction assays have been optimized for cytology smear to investigate aberrant DNA methylation of several NSCLC-related genes.
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Biomarcadores de Tumor/análisis , Carcinoma de Pulmón de Células no Pequeñas/genética , Citodiagnóstico/métodos , Neoplasias Pulmonares/genética , Patología Molecular/métodos , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Análisis Mutacional de ADN/métodos , Humanos , Neoplasias Pulmonares/diagnósticoRESUMEN
INTRODUCTION: Patients with difficult venous access experience undesirable effects during healthcare, such as delayed diagnosis and initiation of treatment, stress and pain related to the technique and reduced satisfaction. This study aims to identify risk factors with which to model the appearance of difficulty in achieving peripheral venous puncture in hospital treatment. METHODS AND ANALYSIS: Case-control study. We will include adult patients requiring peripheral venous cannulation in eight public hospitals, excluding those in emergency situations and women in childbirth or during puerperium. The nurse who performs the technique will record in an anonymised register variables related to the intervention. Subsequently, a researcher will extract the health variables from the patient's medical history. Patients who present one of the following conditions will be assigned to the case group: two or more failed punctures, need for puncture support, need for central access after failure to achieve peripheral access, or decision to reject the technique. The control group will be obtained from records of patients who do not meet the above conditions. It has been stated a minimum sample size of 2070 patients, 207 cases and 1863 controls.A descriptive analysis will be made of the distribution of the phenomenon. The variables hypothesised to be risk factors for the appearance of difficult venous cannulation will be studied using a logistic regression model. ETHICS AND DISSEMINATION: The study was funded in January 2017 and obtained ethical approval from the Research Ethics Committee of the Balearic Islands. Informed consent will be obtained prior to data collection. Results will be published in a peer-reviewed scientific journal.
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Cateterismo Periférico/métodos , Estudios de Casos y Controles , Catéteres Venosos Centrales , Hospitales Públicos , Humanos , Modelos Logísticos , Proyectos de Investigación , Factores de Riesgo , EspañaRESUMEN
La biopsia hepática constituye un excelente método diagnóstico en el espectro de la patología hepática. Para algunos autores la biopsia hepática no es considerada como el "método más indicado" debido al error de muestreo y las variaciones interobservador, sin embargo, sigue considerándose por muchos el "método de elección". Se recopilaron y analizaron en forma retrospectiva, las preparaciones histológicas y las boletas de solicitud de biopsias de todos los casos de biopsias hepáticas, provenientes de la Sección de Patología Gastrointestinal y Hepática "Dr. Pedro Grases" del Instituto Anatomopatológico "Dr. José A. ODaly" de la Universidad Central de Venezuela, en el lapso comprendido entre enero de 1996 y diciembre de 2006. Pacientes 50,8% eran mujeres y 46,8% hombres. El grupo etario más afectado (55,4%) fue entre 31 y 60 años. Los hallazgos clínicos más frecuentes fueron ictericia (7,9%) y dolor en hipocondrio derecho (5,3%). Frecuencia de los diagnósticos histopatológicos: esteatosis (15,1%), hepatitis por virus C (12,3%), tumores metastásicos (8,9%), cirrosis (8,1%), esteatohepatitis (6,6%), patologías vasculares (5,4%), tumores primarios hepáticos (4,1%). La biopsia hepática es una excelente herramienta para el diagnóstico y tratamiento, si se realiza una buena correlación clínico patológica
Liver biopsy is an excellent diagnostic method in the spectrum of liver pathology. For some authors liver biopsy is considered the "best method" due to sampling error and interobserver variations, however is still considered by many the "method of choice". We collected and analyzed retrospectively, the histological preparations and request ballots biopsies of all cases of liver biopsies, from the Section of Gastrointestinal and Liver Pathology "Dr. Pedro Grases "Institute of Pathology" Dr. José A. ODaly "Central University of Venezuela, in the period between January 1996 and December 2006. 50.8% patients were female and 46.8% male. The most affected age group (55.4%) was between 31 and 60 years. The most frequent clinical findings were jaundice (7.9%) and right upper quadrant pain (5.3 %). Frequency of histopathological diagnoses: steatosis (15.1%), hepatitis C virus (12.3%), metastatic tumors (8.9%), cirrhosis (8.1%), steatohepatitis (6.7%), vascular diseases (5.4%), primary liver tumors (4.1%). Liver biopsy is an excellent tool for diagnosis and treatment, if you do a good clinicopathologic correlation
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Femenino , Persona de Mediana Edad , Biopsia/métodos , Cirrosis Hepática/diagnóstico , Hepatitis/diagnóstico , Ictericia/diagnóstico , Ictericia/patología , Patología Clínica/métodos , Pruebas de Función Hepática/métodos , GastroenterologíaRESUMEN
OBJECTIVE: Primary extragonadal germ cell tumors are rare and their histogenetic origin is not clear. We describe two cases presenting as primary retroperitoneal germ cell tumors without clinical evidence of testicular tumor. METHODS: A 21 and 18 years-old patients presented retroperitoneal choriocarcinoma and yolk sac tumor, respectively. In both cases, testicular palpation was not suspicious for testicular cancer. Testicular ultrasound founded alterations in right testes. RESULTS: A right orchitectomy were performed and the final diagnostics were mature teratoma associated with intratubular malignant germ cell. CONCLUSION: Adult mature teratoma is infrequent and the retroperitoneal germ cell tumors should be considered to be metastases of a viable or burned-out testicular cancer.
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Neoplasias de Células Germinales y Embrionarias/diagnóstico , Neoplasias Retroperitoneales/diagnóstico , Adolescente , Adulto , Humanos , Masculino , Neoplasias de Células Germinales y Embrionarias/secundario , Neoplasias Retroperitoneales/secundarioRESUMEN
Se presenta un caso de leiomioma de labio menor izquierdo de vulva en una mujer de 30 años de edad. Se hace una revisión de la bibliografía nacional e internacional en cuanto a la frecuencia de estas lesiones, presentación clínica, diagnóstico diferencia y tratamiento de las misma
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Leiomioma/terapia , Vulva/patología , Leiomioma/patologíaRESUMEN
Se revisaron 156 historias de pacientes que ingresaron a la Unidad de Hipertension Inducida por el Embarazo de enero a diciembre de 1990. En 89,74% el diagnostico fue preeclampsia severa y en 10,26% eclampsia. Se trato de primigestas en 55,13% y 44,87% tenian 2 o mas gestaciones siendo, la edad promedio 27,82 anos. Como antecedentes importantes tuvimos la hipertension inducida por el embarazo, hipertension arterial cronica, obesidad, diabetes y anemia en 68,59%. El edema (30,13%), la cefalea (29,49%) y la epigastralgia (18,59%) fueron los principales sintomas asociados. La edad gestacional fue menor a las 37 semanas en 46,79% y los pesos fetales fueron inferiores a los 2.500 gramos en 37,82%. Para evaluar el bienestar fetal se empleo el perfil biofisico en 26,92% y el embarazo se resolvio por via vaginal en 63,50% y por cesarea en 36,59%. La morbilidad materna fue 23,08% y la mortalidad de 0,64% con una tasa de mortalidad fetal perinatal de 0,91 por mil nacidos vivos
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Embarazo , Adolescente , Adulto , Persona de Mediana Edad , Humanos , Femenino , Preeclampsia , Embarazo , EclampsiaRESUMEN
Reporte de un caso infrecuente de endometriosis extrapélvica y revisión bibliográfica del conocimiento actual sobre el tema. Resumen del caso clínico y búsqueda bibliográfica empleando bases de datos médicos en internet. Servicio de Cirugía II, Hospital Vargas de Caracas. Se describe un raro caso de endometriosis extrapélvica de localización inguinal, con el objeto de recalcar la importancia de incluir a esta enfermedad dentro de los diagnósticos diferenciales en la práctica quirúrgica general. La endometriosis es un diagnóstico ginecológico común. La enfermedad puede estar localizada en cualquier órgano y sistema del organismo planteando dificultades en el diagnóstico y tratamiento. La endometriosis en la región inguinal es poco frecuente, fue descrita por primera vez en 1986 y desde entonces sólo 24 casos han sido reportados. Según el consenso actual el tratamiento para la endometriosis extrapélvica de localización inguinal es quirúrgico. Si de forma simultánea el paciente presenta endometriosis intrapélvica, el tratamiento con terapia supresora puede estar indicado