Venous-plexus-associated lymphoid hubs support meningeal humoral immunity.

There is increasing interest in how immune cells in the meninges-the membranes that surround the brain and spinal cord-contribute to homeostasis and disease in the central nervous system1,2. The outer layer of the meninges, the dura mater, has recently been described to contain both innate and adaptive immune cells, and functions as a site for B cell development3-6. Here we identify organized lymphoid structures that protect fenestrated vasculature in the dura mater. The most elaborate of these dural-associated lymphoid tissues (DALT) surrounded the rostral-rhinal confluence of the sinuses and included lymphatic vessels. We termed this structure, which interfaces with the skull bone marrow and a comparable venous plexus at the skull base, the rostral-rhinal venolymphatic hub. Immune aggregates were present in DALT during homeostasis and expanded with age or after challenge with systemic or nasal antigens. DALT contain germinal centre B cells and support the generation of somatically mutated, antibody-producing cells in response to a nasal pathogen challenge. Inhibition of lymphocyte entry into the rostral-rhinal hub at the time of nasal viral challenge abrogated the generation of germinal centre B cells and class-switched plasma cells, as did perturbation of B-T cell interactions. These data demonstrate a lymphoid structure around vasculature in the dura mater that can sample antigens and rapidly support humoral immune responses after local pathogen challenge.

In vivo labeling reveals continuous trafficking of TCF-1+ T cells between tumor and lymphoid tissue.

Improving the efficacy of immune checkpoint therapies will require a better understanding of how immune cells are recruited and sustained in tumors. Here, we used the photoconversion of the tumor immune cell compartment to identify newly entering lymphocytes, determine how they change over time, and investigate their egress from the tumor. Combining single-cell transcriptomics and flow cytometry, we found that while a diverse mix of CD8 T cell subsets enter the tumor, all CD8 T cells retained within this environment for more than 72 h developed an exhausted phenotype, revealing the rapid establishment of this program. Rather than forming tumor-resident populations, non-effector subsets, which express TCF-1 and include memory and stem-like cells, were continuously recruited into the tumor, but this recruitment was balanced by concurrent egress to the tumor-draining lymph node. Thus, the TCF-1+ CD8 T cell niche in tumors is highly dynamic, with the circulation of cells between the tumor and peripheral lymphoid tissue to bridge systemic and intratumoral responses.

Anogenital distance and anti-Müllerian hormone combined improves the diagnosis of polycystic ovary syndrome.

The objective of this study was to assess the accuracy of the combination of anogenital distance (AGD) and anti-Müllerian hormone (AMH) in the diagnosis of polycystic ovary syndrome (PCOS). The study included women diagnosed with PCOS and a control group who attended the Clinical University Hospital 'Virgen de la Arrixaca' in Murcia (Spain). Serum concentrations of AMH were measured and two AGD measurements were obtained: (i) from the anterior clitoral surface to the upper verge of the anus (AGDAC); and (ii) from the posterior fourchette to the upper verge of the anus (AGDAF). Data were assessed by receiver operator characteristic (ROC) curves. Women with PCOS (n = 126) had significantly larger AGDAC (80.5 ± 11.3 versus 76.0 ± 10.4 mm; p < 0.001) and higher AMH (7.2 ± 4.7 versus 3.1 ± 2.2; p < 0.001) compared to control women (n = 159). Women with serum AMH above 3.8 ng/mL (clinical cut-off used in PCOS) were 9.1 times more likely to have PCOS (95% CI: 5.1-16.2). The area under the ROC curve of combined model of AMH and AGDAC was 0.87 (95% CI: 0.83-0.91). The combined model for predicting PCOS based on AMH and AGDAC has better diagnostic accuracy than that of AMH or AGDAC alone. This model could be useful for clinicians and improve diagnosis and clinical management of these women.

The HIF complex recruits the histone methyltransferase SET1B to activate specific hypoxia-inducible genes.

Hypoxia-inducible transcription factors (HIFs) are fundamental to cellular adaptation to low oxygen levels, but it is unclear how they interact with chromatin and activate their target genes. Here, we use genome-wide mutagenesis to identify genes involved in HIF transcriptional activity, and define a requirement for the histone H3 lysine 4 (H3K4) methyltransferase SET1B. SET1B loss leads to a selective reduction in transcriptional activation of HIF target genes, resulting in impaired cell growth, angiogenesis and tumor establishment in SET1B-deficient xenografts. Mechanistically, we show that SET1B accumulates on chromatin in hypoxia, and is recruited to HIF target genes by the HIF complex. The selective induction of H3K4 trimethylation at HIF target loci is both HIF- and SET1B-dependent and, when impaired, correlates with decreased promoter acetylation and gene expression. Together, these findings show SET1B as a determinant of site-specific histone methylation and provide insight into how HIF target genes are differentially regulated.

Assessment of Optimism in Women with Polycystic Ovary Syndrome: A Case Control-Study.

Polycystic ovary syndrome (PCOS) is a chronic endocrinopathy characterized by hyperandrogenism and anovulation that may pervade psychological dimensions such as dispositional optimism. Considering how PCOS influences mental health and the lack of studies on this matter, this research was aimed at assessing optimism and associated factors in PCOS. A case-control study of 156 patients with PCOS and 117 controls was conducted. All woman filled out the Life Orientation Test-Revised (LOT-R), a self-report questionnaire for measuring dispositional optimism. Medication, pain severity, gynecological, and sociodemographic information was also collected. Lower optimism was found in patients with PCOS compared to controls, even after covariate adjustment (LOT-R global scores: 14.1 vs. 15.9, p = 0.020). Our study provides evidence that a personality characteristic with important implications in illness prognosis may be affected in PCOS. We propose to assess dispositional optimism with the LOT-R scale in the gynecological appointment and tailor medical attention accordingly as a way to improve the comprehensive care of these patients within a multidisciplinary team.

Glutaminase isoforms expression switches microRNA levels and oxidative status in glioblastoma cells.

BACKGROUND: Glutaminase isoenzymes GLS and GLS2 play apparently opposing roles in cancer: GLS acts as an oncoprotein, while GLS2 (GAB isoform) has context specific tumour suppressive activity. Some microRNAs (miRNAs) have been implicated in progression of tumours, including gliomas. The aim was to investigate the effect of GLS and GAB expression on both miRNAs and oxidative status in glioblastoma cells. METHODS: Microarray profiling of miRNA was performed in GLS-silenced LN229 and GAB-transfected T98G human glioblastoma cells and their wild-type counterparts. Results were validated by real-time quantitative RT-PCR. Oxidative status and antioxidant enzymes were determined by spectrophotometric or fluorescence assays in GLS-silenced LN229 and T98G, and GAB-transfected LN229 and T98G. RESULTS: MiRNA-146a-5p, miRNA-140-3p, miRNA-21-5p, miRNA-1260a, and miRNA-92a-3p were downregulated, and miRNA-1246 was upregulated when GLS was knocked down. MiRNA-140-3p, miRNA-1246, miRNA-1260a, miRNA-21-5p, and miRNA-146a-5p were upregulated when GAB was overexpressed. Oxidative status (lipid peroxidation, protein carbonylation, total antioxidant capacity, and glutathione levels), as well as antioxidant enzymes (catalase, superoxide dismutase, and glutathione reductase) of silenced GLS glioblastoma cells and overexpressed GAB glioblastoma cells significantly changed versus their respective control glioblastoma cells. MiRNA-1246, miRNA-1260a, miRNA-146a-5p, and miRNA-21-5p have been characterized as strong biomarkers of glioblastoma proliferation linked to both GLS silencing and GAB overexpression. Total glutathione is a reliable biomarker of glioblastoma oxidative status steadily associated to both GLS silencing and GAB overexpression. CONCLUSIONS: Glutaminase isoenzymes are related to the expression of some miRNAs and may contribute to either tumour progression or suppression through certain miRNA-mediated pathways, proving to be a key tool to switch cancer proliferation and redox status leading to a less malignant phenotype. Accordingly, GLS and GAB expression are especially involved in glutathione-dependent antioxidant defence.

Dynamic regulation of hypoxia-inducible factor-1α activity is essential for normal B cell development.

B lymphocyte development and selection are central to adaptive immunity and self-tolerance. These processes require B cell receptor (BCR) signaling and occur in bone marrow, an environment with variable hypoxia, but whether hypoxia-inducible factor (HIF) is involved is unknown. We show that HIF activity is high in human and murine bone marrow pro-B and pre-B cells and decreases at the immature B cell stage. This stage-specific HIF suppression is required for normal B cell development because genetic activation of HIF-1α in murine B cells led to reduced repertoire diversity, decreased BCR editing and developmental arrest of immature B cells, resulting in reduced peripheral B cell numbers. HIF-1α activation lowered surface BCR, CD19 and B cell-activating factor receptor and increased expression of proapoptotic BIM. BIM deletion rescued the developmental block. Administration of a HIF activator in clinical use markedly reduced bone marrow and transitional B cells, which has therapeutic implications. Together, our work demonstrates that dynamic regulation of HIF-1α is essential for normal B cell development.

Nuclear Translocation of Glutaminase GLS2 in Human Cancer Cells Associates with Proliferation Arrest and Differentiation.

Glutaminase (GA) catalyzes the first step in mitochondrial glutaminolysis playing a key role in cancer metabolic reprogramming. Humans express two types of GA isoforms: GLS and GLS2. GLS isozymes have been consistently related to cell proliferation, but the role of GLS2 in cancer remains poorly understood. GLS2 is repressed in many tumor cells and a better understanding of its function in tumorigenesis may further the development of new therapeutic approaches. We analyzed GLS2 expression in HCC, GBM and neuroblastoma cells, as well as in monkey COS-7 cells. We studied GLS2 expression after induction of differentiation with phorbol ester (PMA) and transduction with the full-length cDNA of GLS2. In parallel, we investigated cell cycle progression and levels of p53, p21 and c-Myc proteins. Using the baculovirus system, human GLS2 protein was overexpressed, purified and analyzed for posttranslational modifications employing a proteomics LC-MS/MS platform. We have demonstrated a dual targeting of GLS2 in human cancer cells. Immunocytochemistry and subcellular fractionation gave consistent results demonstrating nuclear and mitochondrial locations, with the latter being predominant. Nuclear targeting was confirmed in cancer cells overexpressing c-Myc- and GFP-tagged GLS2 proteins. We assessed the subnuclear location finding a widespread distribution of GLS2 in the nucleoplasm without clear overlapping with specific nuclear substructures. GLS2 expression and nuclear accrual notably increased by treatment of SH-SY5Y cells with PMA and it correlated with cell cycle arrest at G2/M, upregulation of tumor suppressor p53 and p21 protein. A similar response was obtained by overexpression of GLS2 in T98G glioma cells, including downregulation of oncogene c-Myc. Furthermore, human GLS2 was identified as being hypusinated by MS analysis, a posttranslational modification which may be relevant for its nuclear targeting and/or function. Our studies provide evidence for a tumor suppressor role of GLS2 in certain types of cancer. The data imply that GLS2 can be regarded as a highly mobile and multilocalizing protein translocated to both mitochondria and nuclei. Upregulation of GLS2 in cancer cells induced an antiproliferative response with cell cycle arrest at the G2/M phase.

Are there differences in basal thrombophilias and C-reactive protein between women with or without PCOS?

RESEARCH QUESTION: Polycystic ovary syndrome (PCOS) women have increased cardiovascular risks, although it is unclear whether the haemostatic system and coagulation contribute to that increased risk. DESIGN: Women attending the Gynecology Unit of the 'Virgen de la Arrixaca' University Hospital (Murcia, Spain) for routine gynaecological examinations between September 2014 and May 2016 were assessed for PCOS using the Rotterdam criteria (hyperandrogenism [H], oligo/amenorrhoea [O] and polycystic ovarian morphology [POM]) and were classified into four phenotypic. In total, 126 cases were identified and 159 control women were selected. All women underwent physical and gynaecological examinations, and blood tests between the second and fifth day of the menstrual cycle. Differences in hormonal, basal thrombophilia and metabolic parameters, and C-reactive protein (CRP) between PCOS and controls were analysed. RESULTS: After adjusting by BMI and age, PCOS women had higher LH (P < 0.001), testosterone (P < 0.001), free testosterone (P = 0.01) and anti-Müllerian hormone (P < 0.001) and lower FSH (P = 0.03) compared with controls, whereas sex hormone-binding globulin was no different. Cases showed significantly higher protein S, glucose, insulin and insulin resistance (HOMA-IR) compared with controls (P < 0.05). There were no differences in protein C levels, antithrombin III, prothrombin time, homocysteine, D-dimer, factor V Leyden, prothrombin G20210A polymorphism or CRP. The H+O phenotype showed the poorest results for insulin and HOMA-IR (P = 0.04 and 0.05). CONCLUSIONS: The results suggest that there are no differences in the basal thrombophilias between women with and without PCOS. However, PCOS with H+O shows the poorest metabolic profile.

Accuracy of anogenital distance and anti-Müllerian hormone in the diagnosis of endometriosis without surgery.

OBJECTIVE: To assess the predictive ability of a combination of anogenital distance (AGD) and anti-Müllerian hormone (AMH) to diagnosis the presence of endometriosis without surgery. METHODS: The present study included women diagnosed with endometriosis and a control group who attended the "Virgen de la Arrixaca" University Hospital, Murcia, Spain, between September 1, 2014, and May 31, 2015. Serum concentrations of AMH were measured, and two AGD measurements were obtained: from the anterior clitoral surface to the upper verge of the anus (AGDAC ), and from the posterior fourchette to the upper verge of the anus (AGDAF ). Data were assessed by receiver operator characteristic (ROC) curves. RESULTS: Women in the endometriosis group (n=57) had significantly shorter AGDAF (22.8 ± 4.6 vs 27.2 ± 5.7 mm; P<0.001) and lower AMH (2.2 ± 2.5 vs 3.3 ± 1.9 ng/mL; P<0.003) compared with the control group (n=93). Women with serum AMH below the clinical cut-off (1 ng/mL) were 17.40-times more likely to have endometriosis (95% confidence interval [CI] 5.64-53.82). The area under the ROC curve of combined AMH and AGDAF was 0.77 (95% CI 0.70-0.85). CONCLUSION: The model for predicting endometriosis on the basis of AMH and AGD could be useful for clinicians and epidemiologists to improve diagnosis and prognosis of this condition.

Assessment of anogenital distance as a diagnostic tool in polycystic ovary syndrome.

RESEARCH QUESTION: Is anogenital distance (AGD) a useful clinical tool for predicting polycystic ovarian syndrome (PCOS) and its main National Institutes of Health (NIH) phenotypes? DESIGN: Case-control study conducted between September 2014 and May 2016 at the Department of Obstetrics and Gynecology of the University Clinical Hospital 'Virgen de la Arrixaca' in the Murcia region (south-eastern Spain). One hundred and twenty-six cases of PCOS and 159 controls without PCOS were included. AGD measurements were taken from the anterior clitoral surface to the upper verge of the anus (AGDAC), and from the posterior fourchette to the upper verge of the anus (AGDAF). Parametric and non-parametric tests and receiver operating characteristic (ROC) curves were used to assess associations between AGD and the presence of PCOS and its phenotypes. RESULTS: AGDAC, but not AGDAF, was associated with PCOS and all its phenotypes (P-values < 0.001 to 0.048). The highest area under the curve (0.62; 95% confidence interval 0.55 to 0.71) was obtained for all PCOS with AGDAC with a sensitivity and specificity of 50.0% and 73.0%, and positive and negative predictive value of 59.0% and 64.4%, respectively. CONCLUSIONS: AGDAC could moderately discriminate the presence of PCOS and may be a useful clinical tool.

Determinantes del estado de salud de la población y su influencia en el desarrollo de los trastornos cognitivos / Determinants of the health status of the population and its influence on the development of cognitive disorders

Introducción: Ante el envejecimiento acelerado de la población cubana los trastornos cognitivos se han convertido en creciente problema y un reto para nuestro sistema de salud. Objetivo: Describir la influencia de las determinantes del estado de salud de la población en el desarrollo de los trastornos cognitivos. Fuente de datos: Se consultaron 113 artículos en la Biblioteca Virtual Scielo y en las bases de datos Medline, Google Scholar, Cochrane y PubMed, en idioma Inglés y Español. Se seleccionaron 40, publicados en revistas nacionales e internacionales de gran impacto, por autores considerados expertos en esta temática. Síntesis de los datos: Además de factores biológicos y genéticos, existen determinantes psicosociales como el nivel educacional y los estilos de vida que pudieran incidir en la aparición y desarrollo de las demencias. Entre estos últimos, aparecen los hábitos tóxicos, las relaciones sociales, antecedentes de depresión, nivel socioeconómico y otros. Conclusiones: La influencia de los determinantes del estado de salud de la población en el desarrollo de los trastornos cognitivos, es notable. Es necesario el estudio de estos determinantes y su contribución a la puesta en marcha de estrategias de intervención comunitaria que ayuden, sobre todo, a la población más vulnerable a tener una mejor calidad de vida(AU).

Introduction: The accelerated aging of the Cuban population is an alert to the high prevalence of dementias and other chronic diseases. Objective: To describe the influence of health status determinants of the population in the development of cognitive disorders. Data source: 113 articles in the Scielo Virtual Library and in Medline, Google Scholar, Cochrane and PubMed databases were consulted, both in English and Spanish. 38 of the selected were published in national and international magazines of great impact, by authors considered experts in this subject. Synthesis of data: In addition to biological and genetic factors, there are other psychosocial determinants such as education and lifestyles that may have an impact on the onset and development of dementia. Among the latter are toxic habits, social interactions, sleep, and depressive states. These states may be considered as a psychological reaction to incipient cognitive worsening or as an early manifestation of dementia. Conclusions: The influence of population´s health status determinants in the development of cognitive disorders is remarkable. Given the accelerated aging of the Cuban population, cognitive disorders become a growing health problem. More research is needed and the results of this may contribute to a better understanding of the epidemiological behavior of these disorders. It is necessary, through intersectoral work, the implementation of community intervention strategies that help above all most vulnerable population to have a better life quality(AU)

Presence of polycystic ovary syndrome is associated with longer anogenital distance in adult Mediterranean women.

STUDY QUESTION: Is polycystic ovary syndrome (PCOS) associated with anogenital distance (AGD), a biomarker of fetal androgen exposure, in adult Mediterranean women? SUMMARY ANSWER: Longer AGD is associated with PCOS in adult Mediterranean women. WHAT IS KNOWN ALREADY: AGD is a biomarker of prenatal androgen milieu. Human observational studies have reported that associations between AGD and reproductive parameters in both sexes. Exposure of the female fetus to intrauterine androgens may be a risk factor for PCOS in adulthood. STUDY DESIGN, SIZE, DURATION: This was a case-control study of 126 women with PCOS and 159 controls between September 2014 and May 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cases were attending the gynecology unit of the 'Virgen de la Arrixaca' University Clinical Hospital (Murcia, Spain), and were diagnosed following the Rotterdam criteria. Phenotypic subtypes of PCOS were also assessed. Both prevalent and incident (newly diagnosed) cases were included. Controls were women without PCOS attending the gynecological outpatient clinic for routine gynecological exams. All women completed health questionnaires, and underwent physical and gynecological examinations, including transvaginal ultrasound and blood draw. We obtained measures from the anterior clitoral surface to the upper verge of the anus (AGDAC), and from the posterior fourchette to the upper verge of the anus (AGDAF). Gynecologists performing the AGD measures were blind to the status of the patients. We used unconditional multiple logistic regression to evaluate the association between AGD measurements and PCOS while accounting for relevant covariates and confounders, such as BMI, age and episiotomy. MAIN RESULTS AND THE ROLE OF CHANCE: Cases showed significantly longer AGDAF and AGDAC compared to controls in bivariate analyses (P-values < 0.05). In the final adjusted models, AGDAC, but not AGDAF, was associated with the presence of PCOS (P-values = 0.002-0.008). Women with AGDAC in the upper compared to the lowest tertile were 2.9-times (95% CI 1.4-5.9; P-trend = 0.008) more likely to have PCOS. AGDAC measures were also significantly associated with all of the different phenotypic subtypes of PCOS (ORs = 3.1-5.1; P-values < 0.05). LIMITATIONS REASONS FOR CAUTION: We took into account known and suspected covariates and confounders, but the possibility of chance findings or residual confounding should be noted. As with all observational studies, causal inference is limited, and study selection and information bias should not be ruled out. WIDER IMPLICATIONS OF THE FINDINGS: Our results support the hypothesis that PCOS has an intrauterine origin, and that the hormonal environment in which the fetus develops may be highly relevant. STUDY FUNDING/COMPETING INTEREST: This work was supported by the Ministry of Economy and Competitiveness, Instituto de Salud Carlos III (ISCIII) (AES, Acción Estratégica en Salud), grant No. PI13/01237, and The Seneca Foundation, Murcia Regional Agency of Science and Technology, grant No. 19443/PI/14. There are no competing interests. TRIAL REGISTRATION NUMBER: Not applicable.

Use of Eye Tracking as an Innovative Instructional Method in Surgical Human Anatomy.

OBJECTIVE: Tobii glasses can record corneal infrared light reflection to track pupil position and to map gaze focusing in the video recording. Eye tracking has been proposed for use in training and coaching as a visually guided control interface. The aim of our study was to test the potential use of these glasses in various situations: explanations of anatomical structures on tablet-type electronic devices, explanations of anatomical models and dissected cadavers, and during the prosection thereof. An additional aim of the study was to test the use of the glasses during laparoscopies performed on Thiel-embalmed cadavers (that allows pneumoinsufflation and exact reproduction of the laparoscopic surgical technique). The device was also tried out in actual surgery (both laparoscopy and open surgery). DESIGN: We performed a pilot study using the Tobii glasses. SETTING: Dissection room at our School of Medicine and in the operating room at our Hospital. PARTICIPANTS: To evaluate usefulness, a survey was designed for use among students, instructors, and practicing physicians. RESULTS: The results were satisfactory, with the usefulness of this tool supported by more than 80% positive responses to most questions. There was no inconvenience for surgeons and that patient safety was ensured in the real laparoscopy. CONCLUSION: To our knowledge, this is the first publication to demonstrate the usefulness of eye tracking in practical instruction of human anatomy, as well as in teaching clinical anatomy and surgical techniques in the dissection and operating rooms.

Glutaminases in brain: Multiple isoforms for many purposes.

Glutaminase is expressed in most mammalian tissues and cancer cells, but recent studies are now revealing a considerably degree of complexity in its pattern of expression and functional regulation. Novel transcript variants of the mammalian glutaminase Gls2 gene have been recently found and characterized in brain. Co-expression of different isoforms in the same cell type would allow cells to fine-tune their Gln/Glu levels under a wide range of metabolic states. Moreover, the discovery of protein interacting partners and novel subcellular localizations, for example nucleocytoplasmic in neurons and astrocytes, strongly suggest non-neurotransmission roles for Gls2 isoforms associated with transcriptional regulation and cellular differentiation. Of note, Gls isoforms have been considered as an important trophic factor for neuronal differentiation and postnatal development of brain regions. On the other hand, glutaminases are taking center stage in tumor biology as new therapeutic targets to inhibit metabolic reprogramming of cancer cells. Interestingly, glutaminase isoenzymes play seemingly opposing roles in cancer cell growth and proliferation; this issue will be also succinctly discussed with special emphasis on brain tumors.

The Manchester-Fothergill and the Elevate Posterior technique for the correction of a cervical elongation and large enterocele in a patient with bladder exstrophy and multiple surgeries.

INTRODUCTION AND HYPOTHESIS: A 60-year-old woman presented with congenital bladder exstrophy, urinary incontinence since birth, and pelvic organ prolapse since the menopause at the age of 46 years. METHODS: The patient (gravida 2, para 2 by cesarean sections and tubal ligation) described an extensive past surgical history that included epispadias and neourethral procedures, anti-reflux surgery using the Lich-Grégoir technique, bilateral ureterosigmoidostomy achieving continence, uterine fixation after the Doléris operation, and neovaginal reconstruction. The physical examination revealed a fourth-degree enterocele with cervical elongation (POP-Q: Aa-2, Ba-2, C + 3, D + 4, gh:5, pb:2.5, Tvl:6, Ap + 3, Bp +6). Gynecological ultrasound and uro-CT were performed to ensure that the ureterosigmoidostomy had been successful, and CT-based 3D bone reconstructions were obtained to calculate the distance between the pubic rami and the ischial spines. Based on a literature review of the management options for these patients and the specific characteristics of our patient, a decision was made to perform trachelectomy (the Manchester technique with Fothergill stitches) and a polypropylene mesh placement with sacrospinous ligament anchor (Elevate Posterior® PC, AMS). RESULTS: Six months after the surgery, we observed good anatomical and functional results with significant improvement in the patient's quality-of-life scale score. CONCLUSION: We believed that the vaginal approach was minimally invasive with a low risk of morbidity in our patient, who had a very altered anatomy, but produced a satisfactory functional result.