Miguel Andújar

Complejo Hospitalario Universitario Insular - Materno Infantil de Canarias, Las Palmas, Canary Islands, Spain

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Publications (16)92.77 Total impact

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    ABSTRACT: We present the case of a 17-year-old nulliparous woman with a history of obesity (BMI 36.2), type-2 diabetes and Polycystic Ovary Syndrome, diagnosed with grade-1 endometrioid adenocarcinoma without radiological evidence of myometrial invasion or metastatic disease. After failure of a fertility-preserving treatment with a levonorgestrel-releasing intrauterine device, bariatric surgery was proposed to treat obesity and improve control for her type-2 diabetes in an attempt to increase the chances of obtaining response to local treatment. Nine months after laparoscopic sleeve gastrectomy and eighteen months after insertion of the intrauterine device the patient reached normal body weight (BMI 20.3) and showed complete response to treatment. As far as we know, this is the first published case of an adolescent obese patient treated with bariatric surgery concomitantly with fertility-preserving management of endometrial cancer. We propose that bariatric surgery may play a role as an adjuvant therapy in fertility-preserving treatment of endometrial cancer with local progestin, where it could enhance remission rates and reduce recurrence. Copyright © 2015 AAGL. Published by Elsevier Inc. All rights reserved.
    No preview · Article · Apr 2015 · Journal of Minimally Invasive Gynecology
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    ABSTRACT: Contribution over time of human papillomavirus (HPV) types in human cancers has been poorly documented. Such data is fundamental to measure current HPV vaccines impact in the years to come. We estimated the HPV type-specific distribution in a large international series of invasive cervical cancer (ICC) over 70 years prior to vaccination. Paraffin embedded ICC cases diagnosed between 1940 and 2007 were retrieved from eleven countries in Central-South America, Asia and Europe. Included countries reported to have low-medium cervical cancer screening uptake. Information on age at and year of diagnosis was collected from medical records. After histological confirmation, HPV DNA detection was performed by SPF-10/DEIA/LiPA25 (version1). Logistic regression models were used for estimating the adjusted relative contributions (RC) of HPV16 and of HPV18 over time. Among 4,771 HPV DNA positive ICC cases, HPV16 and HPV18 were the two most common HPVs in all the decades with no statistically significant variations of their adjusted-RC from 1940–59 to 2000–07 (HPV16—from 61.5 to 62.1%, and HPV18—from 6.9 to 7.2%). As well, the RC of other HPV types did not varied over time. In the stratified analysis by histology, HPV16 adjusted-RC significantly increased across decades in adenocarcinomas. Regarding age, cases associated to either HPV16, 18 or 45 were younger than those with other HPV types in all the evaluated decades. The observed stability on the HPV type distribution predicts a high and stable impact of HPV vaccination in reducing the cervical cancer burden in future vaccinated generations.
    Full-text · Article · Jul 2014 · International Journal of Cancer
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    ABSTRACT: Macrophages are professional phagocytic cells that orchestrate innate immune responses and have considerable phenotypic diversity at different anatomical locations. However, the mechanisms that control the heterogeneity of tissue macrophages are not well characterized. Here we found that the nuclear receptor LXRα was essential for the differentiation of macrophages in the marginal zone (MZ) of the spleen. LXR-deficient mice were defective in the generation of MZ and metallophilic macrophages, which resulted in abnormal responses to blood-borne antigens. Myeloid-specific expression of LXRα or adoptive transfer of wild-type monocytes restored the MZ microenvironment in LXRα-deficient mice. Our results demonstrate that signaling via LXRα in myeloid cells is crucial for the generation of splenic MZ macrophages and identify an unprecedented role for a nuclear receptor in the generation of specialized macrophage subsets.
    Full-text · Article · Jun 2013 · Nature Immunology
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    ABSTRACT: The hMSH2(M688R) mismatch repair (MMR) gene mutation has been found in five large families from Tenerife, Spain, suggesting it is a Lynch syndrome or hereditary non-polyposis colorectal cancer (LS/HNPCC) founder mutation. In addition to classical LS/HNPCC tumors, these families present with a high incidence of central nervous system (CNS) tumors normally associated with Turcot or constitutional mismatch repair deficiency (CMMR-D) syndromes. Turcot and CMMR-D mutations may be biallelic, knocking out both copies of the MMR gene. The hMSH2(M688R) mutation is located in the ATP hydrolysis (ATPase) domain. We show that the hMSH2(M688R)-hMSH6 heterodimer binds to mismatched nucleotides but lacks normal ATP functions and inhibits MMR in vitro when mixed with the wild-type (WT) heterodimer. Another alteration that has been associated with LS/HNPCC, hMSH2(M688I)-hMSH6, displays no identifiable differences with the WT heterodimer. Interestingly, some extracolonic tumors from hMSH2(M688R) carriers may express hMSH2-hMSH6, yet display microsatellite instability (MSI). The functional analysis along with variability in tumor expression and the high incidence of CNS tumors suggests that hMSH2(M688R) may act as a dominant negative in some tissues, while the hMSH2(M688I) is most likely a benign polymorphism.
    Full-text · Article · Jun 2012 · Carcinogenesis
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    ABSTRACT: The study's aim was to evaluate the feasibility of laparoscopic extraperitoneal para-aortic lymphadenectomy at a peripheral center for the staging of patients with locally advanced cervical cancer (LACC). From March 2009 to January 2011, 30 patients with LACC underwent laparoscopic extraperitoneal para-aortic lymphadenectomy. All patients were treated with definitive radiotherapy tailored according to the staging results. Data on demographics, pathologic findings, surgery, complications, and disease status at follow-up are presented. Patients' mean age was 47.6 years (range, 28-67 years). The mean body mass index was 26.3 (range, 19.1-35.6). Mean operative time was 118.7 minutes (range, 77-195 minutes) with an average of 14.2 lymph nodes removed (range, 5-34). Intraoperative complications were a lumbar artery injury and a bowel injury. No postoperative complications occurred. Mean postoperative hospital stay was 1.9 days (range, 1-6 days). Pathological examination revealed that 26.7% (8/30) of patients had metastatic disease in para-aortic lymph nodes. Two patients with disease at the para-aortic level died 5 and 12 months after diagnosis; both of them developed pulmonary and hepatic metastases. The rest of the patients were free of disease, after completion of the treatment, during a mean follow-up time of 15.6 months (range, 5-27 months). Laparoscopic extraperitoneal aortic lymphadenectomy is a feasible procedure, even at peripheral centers, that is useful to identify patients with LACC and para-aortic disease and to tailor their treatment. Gynecologic oncologists are encouraged to learn this procedure and offer it to their patients.
    No preview · Article · Dec 2011 · International Journal of Gynecological Cancer
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    ABSTRACT: Human papillomavirus (HPV) genotype distribution in invasive cervical cancer (ICC) is critical to guide the introduction and to assess the impact of HPV prophylactic vaccines. This study aims to provide specific information for Spain. 1043 histological confirmed ICC cases diagnosed from 1940 to 2007 from six Spanish regions were assembled. HPV DNA detection was performed by SPF(10) broad-spectrum PCR followed by deoxyribonucleic acid enzyme immunoassay and genotyping by reverse hybridization line probe assay (LiPA(25)) (version 1). Of 1043 ICC cases, 904 were HPV DNA positive (adjusted prevalence: 89.1%). The eight most common types, in decreasing order, were HPV 16, 18, 33, 31, 45, 35, 52 and 56, accounting for more than 90% of cases. HPV 16 and 18 contributed to 72.4% of all HPV positive ICC cases. In cervical adenocarcinomas, this contribution increased up to 94%. HPV 16 and 18 relative contributions showed a stable pattern over the 60 year study period. HPV 45, 18 and 16-positive ICC cases presented at younger ages than cases with other HPV types (adjusted mean age: 43.8, 45.2, 52.6 and 57.7 years, respectively). HPV 16 and 18 accounted together for a 72.4% of positive cases, with no statistically significant changes in their relative contributions over the last decades. In 94% of cervical adenocarcinomas we identified at least one of the two HPV types included in the current vaccines (HPV 16/18). Results suggest a major impact of HPV vaccines on reduction of ICC burden in Spain in the HPV vaccinated cohorts.
    No preview · Article · Nov 2011 · Gynecologic Oncology
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    ABSTRACT: To evaluate the clinical outcome and pathological features of patients with borderline ovarian tumors (BOT) with special emphasis on serous and mucinous histology. Medical and anatomopathological records were reviewed in the Gynecological Oncology Department of the Canarian University Hospital between 1990 and 2005. Survival rates were analyzed by using the Kaplan-Meier technique. The study included 163 patients. Serous tumors corresponded to 68 cases and mucinous tumors to 91 cases. Eighty-nine percent of patients were at FIGO stage I, 1.2% at stage II and 9.8% at stage III. Serous histology was significantly related to the presence of peritoneal implants (22.4% vs 3.6%; p=0.001), positive peritoneal cytology (35.7% vs 8.5%; p=0.001) and bilaterality (27.9% vs 1.1%, p<0.0001). Event-free survival (EFS) rates at 2, 5 and 10 years were 96.7%, 92.7% and 90.5%, respectively, with a mean survival time of 183 months (CI 95% 172-193). Thirteen recurrence cases were found (7.9%) with a mean time to recurrence of 39.6 months (range 4-140). Overall survival (OS) rates at 2, 5 and 10 years were 100%, 96.4% and 93.6%, respectively, with a mean time of 189 months (CI 95% 179-198). Mucinous BOT were associated with significantly lower OS rates than serous BOT (10 years OS: 88.5% vs 98.2%; p=0.01). Serous tumors present more unfavorable anatomopathological characteristics but are associated with better prognosis than mucinous tumors. If mucinous BOT diagnosis is retained physicians should be aware that their aggressive potential is not negligible.
    No preview · Article · Dec 2010 · European journal of obstetrics, gynecology, and reproductive biology
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    ABSTRACT: Knowledge about the distribution of human papillomavirus (HPV) genotypes in invasive cervical cancer is crucial to guide the introduction of prophylactic vaccines. We aimed to provide novel and comprehensive data about the worldwide genotype distribution in patients with invasive cervical cancer. Paraffin-embedded samples of histologically confirmed cases of invasive cervical cancer were collected from 38 countries in Europe, North America, central South America, Africa, Asia, and Oceania. Inclusion criteria were a pathological confirmation of a primary invasive cervical cancer of epithelial origin in the tissue sample selected for analysis of HPV DNA, and information about the year of diagnosis. HPV detection was done by use of PCR with SPF-10 broad-spectrum primers followed by DNA enzyme immunoassay and genotyping with a reverse hybridisation line probe assay. Sequence analysis was done to characterise HPV-positive samples with unknown HPV types. Data analyses included algorithms of multiple infections to estimate type-specific relative contributions. 22,661 paraffin-embedded samples were obtained from 14,249 women. 10,575 cases of invasive cervical cancer were included in the study, and 8977 (85%) of these were positive for HPV DNA. The most common HPV types were 16, 18, 31, 33, 35, 45, 52, and 58 with a combined worldwide relative contribution of 8196 of 8977 (91%, 95% CI 90-92). HPV types 16 and 18 were detected in 6357 of 8977 of cases (71%, 70-72) of invasive cervical cancer. HPV types 16, 18, and 45 were detected in 443 of 470 cases (94%, 92-96) of cervical adenocarcinomas. Unknown HPV types that were identified with sequence analysis were 26, 30, 61, 67, 69, 82, and 91 in 103 (1%) of 8977 cases of invasive cervical cancer. Women with invasive cervical cancers related to HPV types 16, 18, or 45 presented at a younger mean age than did those with other HPV types (50·0 years [49·6-50·4], 48·2 years [47·3-49·2], 46·8 years [46·6-48·1], and 55·5 years [54·9-56·1], respectively). To our knowledge, this study is the largest assessment of HPV genotypes to date. HPV types 16, 18, 31, 33, 35, 45, 52, and 58 should be given priority when the cross-protective effects of current vaccines are assessed, and for formulation of recommendations for the use of second-generation polyvalent HPV vaccines. Our results also suggest that type-specific high-risk HPV-DNA-based screening tests and protocols should focus on HPV types 16, 18, and 45.
    No preview · Article · Oct 2010 · The Lancet Oncology
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    ABSTRACT: Effective clearance of apoptotic cells by macrophages is essential for immune homeostasis. The transcriptional pathways that allow macrophages to sense and respond to apoptotic cells are poorly defined. We found that liver X receptor (LXR) signaling was important for both apoptotic cell clearance and the maintenance of immune tolerance. Apoptotic cell engulfment activated LXR and thereby induced the expression of Mer, a receptor tyrosine kinase critical for phagocytosis. LXR-deficient macrophages exhibited a selective defect in phagocytosis of apoptotic cells and an aberrant proinflammatory response to them. As a consequence of these defects, mice lacking LXRs manifested a breakdown in self-tolerance and developed autoantibodies and autoimmune glomerulonephritis. Treatment with an LXR agonist ameliorated disease progression in a mouse model of lupus-like autoimmunity. Thus, activation of LXR by apoptotic cells engages a virtuous cycle that promotes their own clearance and couples engulfment to the suppression of inflammatory pathways.
    Full-text · Article · Aug 2009 · Immunity
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    ABSTRACT: To evaluate the clinicopathologic data and prognostic factors for patients with uterine sarcomas treated at a single institution, with special emphasis on malignant mixed müllerian tumors (MMMT). Medical and anatomic pathology records were reviewed. Survival rates were analyzed using the Kaplan-Meier method. The study included 89 patients: 48.4% with MMMT; 22.4% with leiomyosarcomas; 20.2% with endometrial stromal sarcomas; and 9% with adenosarcomas. FIGO stages I, II, III, and IV were identified in 57.3%, 9.0%, 22.5%, and 7.8% of patients respectively. Event-free survival rates after 2, 5, and 10 years were 70%, 61%, and 55% respectively, with a median time of 90 months (95% CI, 41-140 months). Overall survival rates after 2, 5, and 10 years were 50%, 45%, and 39% respectively, with a median time of 43 months (95% CI, 3-83 months). Multivariate analysis showed that stage, histology, tumor size, and parity had an independent influence on overall survival. MMMT are the most aggressive tumors and their behavior strongly resembles that of high-grade endometrial adenocarcinoma. Prognostic factors affecting survival were stage, histology, tumor size, and parity.
    No preview · Article · Jul 2009 · International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics

  • No preview · Article · Nov 2008 · International Journal of Gynecology & Obstetrics
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    ABSTRACT: Villoglandular papillary adenocarcinoma (VPA) is a rare subtype of adenocarcinoma of the uterine cervix. A conservative surgical approach is considered feasible. Only three cases of VPA and pregnancy have been reported. A 34-year-old asymptomatic woman was diagnosed of a well-differentiated VPA without extracervical spread of the disease. A cold knife conization was performed. Five years later, the patient became pregnant. The pregnancy developed without complications and was finished with a caesarean delivery, due to nonreassuring fetal status. A healthy child was born. Last control 8 years later showed no evidence of disease. A successful pregnancy can be completed in patients with VPA without lymph-vascular invasion treated in a conservative way. This management is particularly desirable in young women to preserve reproductive capability.
    No preview · Article · May 2006 · Gynecologic Oncology
  • N. Medina · A. Martín · V. Guillén · M. Andújar · J.A. García
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    ABSTRACT: Paciente de 74 años, remitida a la consulta de ginecología de nuestro hospital por tumoración pélvica de unos 12 cm. La paciente refiere dolor crónico en fosa ilíaca izquierda que aumenta en los últimos meses. La ecografía abdominal muestra una formación quística de 116 × 96 mm, de contenido denso sin tabiques ni papilas. Los marcadores tumorales fueron negativos. Se practica histerectomía y doble anexectomía, y el estudio anatomopatológico informó de endometrioma de ovario izquierdo.
    No preview · Article · Mar 2005 · Progresos de Obstetricia y Ginecología
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    Full-text · Article · Jan 2003
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    ABSTRACT: We studied thirty-three cases of patients diagnosticated of uterine sarcoma, which represent 4% of all the primary gynecological tumors diagnosticated at the Oncological Ginecology Departament of our Hospital. Malignant Mixed Mullerian Tumors (MMMT) represent 58% of all the cases, Leiomyosarcoma (LMS) 30% and endometrial Stromal Sarcoma (ESS) 9%. Age at diagnosis, first symptomatology, moment of diagnosis (before or after surgery), therapy used and survival are studied. Abnormal vaginal bleeding is the most frequent presenting symptom (71%). Important preoperatory rate is found (66,6%) because of the higher frequency of MMMT. The 2 and 5 years global survival rates founded are 48% and 36%, with a 2 and 5 years recurrence rates of 48% and 56%. Significative differences among survival rates obtained are seen in fact of stage, not found when comparing histologic types.
    No preview · Article · Jan 1998
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Publication Stats

904 Citations
92.77 Total Impact Points

Institutions

  • 2006-2015
    • Complejo Hospitalario Universitario Insular - Materno Infantil de Canarias
      Las Palmas, Canary Islands, Spain
  • 2010-2014
    • Universidad de Las Palmas de Gran Canaria
      Las Palmas, Canary Islands, Spain
  • 2008-2009
    • Hospital Universitario de Canarias
      San Cristóbal de La Laguna, Canary Islands, Spain