CANVAS: A New Genetic Entity in the Otorhinolaryngologist's Differential Diagnosis.

OBJECTIVE: The biallelic inheritance of an expanded intronic pentamer (AAGGG)exp in the gene encoding replication factor C subunit 1 (RFC1) has been found to be a cause of cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS). This study describes clinical and genetic features of our patients with clinical suspicion of the syndrome. STUDY DESIGN: A retrospective descriptive study from an ataxia database comprising 500 patients. SETTING: The study was performed at the Otorhinolaryngology Department of a hospital in the north of Spain. METHODS: Specific genetic testing for CANVAS was performed in 13 patients with clinical suspicion of complete or incomplete syndrome. The clinical diagnosis was supported by quantitative vestibular hypofunction, cerebellar atrophy, and abnormal sensory nerve conduction testing. RESULTS: Nine of 13 (69%) patients met clinical diagnostic criteria for definite CANVAS disease. The first manifestation of the syndrome was lower limb dysesthesia in 8 of 13 patients and gait imbalance in 5 of 13. Eleven of 13 (85%) patients were carriers of the biallelic (AAGGG)exp in RFC1. CONCLUSION: A genetic cause of CANVAS has recently been discovered. We propose genetic screening for biallelic expansions of the AAGGG pentamer of RFC1 in all patients with clinical suspicion of CANVAS, since accurate early diagnosis could improve the quality of life of these patients.

Next-generation sequencing for identification of actionable gene mutations in intestinal-type sinonasal adenocarcinoma.

Intestinal-type sinonasal adenocarcinoma (ITAC) is a rare tumor carrying poor prognosis and needing new treatment options. The aim of this study was to identify actionable gene mutations that can guide new personalized target-specific therapies in ITAC patients. A series of 48 tumor and 27 corresponding germline DNA samples were analyzed by next generation sequencing using a panel of 120 genes. In total, 223 sequence variants were found in 70 genes. Matched tumor/germline comparison in 27 cases revealed that 57% were in fact germline variants. In 20 of these 27 cases, 58 somatic variants in 33 different genes were identified, the most frequent being PIK3CA (5 cases), APC and ATM (4 cases), and KRAS, NF1, LRP1B and BRCA1 (3 cases). Many of the somatic gene variants affected PI3K, MAPK/ERK, WNT and DNA repair signaling pathways, although not in a mutually exclusive manner. None of the alterations were related to histological ITAC subtype, tumor stage or survival. Our data showed that thorough interpretation of somatic mutations requires sequencing analysis of the corresponding germline DNA. Potentially actionable somatic mutations were found in 20 of 27 cases, 8 of which being biomarkers of FDA-approved targeted therapies. Our data implicate new possibilities for personalized treatment of ITAC patients.

The presence of dysphagia in patients with cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS): a subjective and objective study.

PURPOSE: The aim of this study was to determine the prevalence of dysphagia in patients with cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS), characterizing this condition, both in its objective dimension and in terms of quality of life (QoL). METHODS: A cross-sectional study was developed in 11 patients diagnosed of CANVAS. In all patients, clinical records were reviewed and the Eating assessment tool 10 (EAT-10) was performed as screening of oropharyngeal dysphagia. To evaluate the QoL impairment secondary to dysphagia, we applied the swallowing quality of life questionnaire (SWAL-QOL) and the MD Anderson Dysphagia Inventory (MDADI). To evaluate the deglutition mechanisms impaired, two objective-instrumental studies were performed: the volume-viscosity swallow test (V-VST) and the fiberoptic endoscopic evaluation of swallowing (FEES). RESULTS: 82% of the patients presented an abnormal EAT-10 score. A correlation was found between the EAT-10 and MDADI and between both QoL questionnaires. After the FEES and V-VST analysis, all 11 patients presented some degree of swallow effectiveness impairment, and most of them safety alterations as well. CONCLUSION: CANVAS remains an underestimated and underdiagnosed condition and the prevalence of swallowing disorders in those patients is higher than expected. Despite the possibility that EAT-10 works as a useful screening test to predict the results in the QoL questionnaires, the absence of correlation between QoL test and instrumental results suggests that to properly evaluate the patients swallowing status, objective instrumental procedures must be conducted.

Radixin modulates the function of outer hair cell stereocilia.

The stereocilia of the inner ear sensory cells contain the actin-binding protein radixin, encoded by RDX. Radixin is important for hearing but remains functionally obscure. To determine how radixin influences hearing sensitivity, we used a custom rapid imaging technique to visualize stereocilia motion while measuring electrical potential amplitudes during acoustic stimulation. Radixin inhibition decreased sound-evoked electrical potentials. Other functional measures, including electrically induced sensory cell motility and sound-evoked stereocilia deflections, showed a minor amplitude increase. These unique functional alterations demonstrate radixin as necessary for conversion of sound into electrical signals at acoustic rates. We identified patients with RDX variants with normal hearing at birth who showed rapidly deteriorating hearing during the first months of life. This may be overlooked by newborn hearing screening and explained by multiple disturbances in postnatal sensory cells. We conclude radixin is necessary for ensuring normal conversion of sound to electrical signals in the inner ear.

Utilidad clínica de la secuenciación de nueva generación en el diagnóstico etiológico de la hipoacusia neurosensorial en una Unidad de Hipoacusia Infantil / Clinical utility of next-generation sequencing in the aetiological diagnosis of sensorineural hearing loss in a Childhood Hearing Loss Unit

INTRODUCCIÓN: La hipoacusia neurosensorial (HNS) es el déficit sensorial más prevalente en nuestro medio. La secuenciación genómica de nueva generación (NGS) permite obtener un diagnóstico etiológico en un alto porcentaje de pacientes. Nuestro estudio piloto muestra los resultados de la aplicación sistemática de la NGS en una Unidad de Hipoacusia Infantil, así como sus implicaciones en el manejo clínico de los pacientes y sus familiares. MATERIAL Y MÉTODO: Se incluyó a 27 pacientes diagnosticados de HNS entre 2014 y 2017 en los que se descartó una causa ambiental. El test genético consistió en un panel de genes analizados mediante NGS (panel OTOgenicsTM). Este panel ha sido diseñado para incluir genes asociados con hipoacusia neurosensorial o mixta, de inicio precoz o tardío, sindrómica y no sindrómica, independientemente de su patrón de herencia. RESULTADOS: Se obtuvo un diagnóstico genético en el 56% (15/27) de los pacientes (62% en el caso de las HNS bilaterales); 5/27 (19%) presentaron variantes patogénicas en el gen GJB2 y el resto variantes patogénicas o probablemente patogénicas en otros genes asociados con HNS aislada (PR2X2, TECTA y STRC), con HNS sindrómicas (CHD7, GATA3, COL4A5, MITF y SOX10) o con HNS sindrómicas y no sindrómicas (BSND, ACTG1 y CDH23). DISCUSIÓN: El diagnóstico etiológico de la HNS supone un desafío en la práctica clínica. Nuestra serie demuestra que es posible implementar el diagnóstico genético en la rutina asistencial y que esta información tiene implicaciones pronósticas y terapéuticas

INTRODUCTION: Sensorineural hearing loss (SNL) is the most prevalent sensory deficit in our environment. Next generation genomic sequencing (NGS) enables an aetiological diagnosis in a high percentage of patients. Our pilot study shows the results of the systematic application of NGS in a Childhood Hearing Loss Unit, as well as its implications for the clinical management of patients and their families. MATERIAL AND METHOD: We included 27 patients diagnosed with SNL between 2014 and 2017, in which an environmental cause was ruled out. The genetic test consisted of a panel of genes analyzed by NGS (OTOgenicsTM panel). This panel has been designed to include genes associated with sensorineural or mixed hearing loss, early onset or late, syndromic and non-syndromic, regardless of their inheritance pattern. RESULTS: A genetic diagnosis was obtained in 56% (15/27) of the patients (62% in the case of bilateral SNL). Of the patients, 5/27 (19%) presented pathogenic variants in the GJB2 gene and the rest pathogenic and / or probably pathogenic variants in other genes associated with isolated SNL (PR2X2, TECTA and STRC), with syndromic SNL (CHD7, GATA3, COL4A5, MITF and SOX10) or with syndromic and non-syndromic SNL (BSND, ACTG1 and CDH23). DISCUSSION: The aetiological diagnosis of SNL is a challenge in clinical practice. Our series demonstrates that it is possible to implement genetic diagnosis in the care routine and that this information has prognostic and therapeutic implications

Clinical utility of next-generation sequencing in the aetiological diagnosis of sensorineural hearing loss in a Childhood Hearing Loss Unit. / Utilidad clínica de la secuenciación de nueva generación en el diagnóstico etiológico de la hipoacusia neurosensorial en una Unidad de Hipoacusia Infantil.

INTRODUCTION: Sensorineural hearing loss (SNL) is the most prevalent sensory deficit in our environment. Next generation genomic sequencing (NGS) enables an aetiological diagnosis in a high percentage of patients. Our pilot study shows the results of the systematic application of NGS in a Childhood Hearing Loss Unit, as well as its implications for the clinical management of patients and their families. MATERIAL AND METHOD: We included 27 patients diagnosed with SNL between 2014 and 2017, in which an environmental cause was ruled out. The genetic test consisted of a panel of genes analyzed by NGS (OTOgenicsTM panel). This panel has been designed to include genes associated with sensorineural or mixed hearing loss, early onset or late, syndromic and non-syndromic, regardless of their inheritance pattern. RESULTS: A genetic diagnosis was obtained in 56% (15/27) of the patients (62% in the case of bilateral SNL). Of the patients, 5/27 (19%) presented pathogenic variants in the GJB2 gene and the rest pathogenic and / or probably pathogenic variants in other genes associated with isolated SNL (PR2X2, TECTA and STRC), with syndromic SNL (CHD7, GATA3, COL4A5, MITF and SOX10) or with syndromic and non-syndromic SNL (BSND, ACTG1 and CDH23). DISCUSSION: The aetiological diagnosis of SNL is a challenge in clinical practice. Our series demonstrates that it is possible to implement genetic diagnosis in the care routine and that this information has prognostic and therapeutic implications.

Comprehensive genomic diagnosis of non-syndromic and syndromic hereditary hearing loss in Spanish patients.

BACKGROUND: Sensorineural hearing loss (SNHL) is the most common sensory impairment. Comprehensive next-generation sequencing (NGS) has become the standard for the etiological diagnosis of early-onset SNHL. However, accurate selection of target genomic regions (gene panel/exome/genome), analytical performance and variant interpretation remain relevant difficulties for its clinical implementation. METHODS: We developed a novel NGS panel with 199 genes associated with non-syndromic and/or syndromic SNHL. We evaluated the analytical sensitivity and specificity of the panel on 1624 known single nucleotide variants (SNVs) and indels on a mixture of genomic DNA from 10 previously characterized lymphoblastoid cell lines, and analyzed 50 Spanish patients with presumed hereditary SNHL not caused by GJB2/GJB6, OTOF nor MT-RNR1 mutations. RESULTS: The analytical sensitivity of the test to detect SNVs and indels on the DNA mixture from the cell lines was > 99.5%, with a specificity > 99.9%. The diagnostic yield on the SNHL patients was 42% (21/50): 47.6% (10/21) with autosomal recessive inheritance pattern (BSND, CDH23, MYO15A, STRC [n = 2], USH2A [n = 3], RDX, SLC26A4); 38.1% (8/21) autosomal dominant (ACTG1 [n = 3; 2 de novo], CHD7, GATA3 [de novo], MITF, P2RX2, SOX10), and 14.3% (3/21) X-linked (COL4A5 [de novo], POU3F4, PRPS1). 46.9% of causative variants (15/32) were not in the databases. 28.6% of genetically diagnosed cases (6/21) had previously undetected syndromes (Barakat, Usher type 2A [n = 3] and Waardenburg [n = 2]). 19% of genetic diagnoses (4/21) were attributable to large deletions/duplications (STRC deletion [n = 2]; partial CDH23 duplication; RDX exon 2 deletion). CONCLUSIONS: In the era of precision medicine, obtaining an etiologic diagnosis of SNHL is imperative. Here, we contribute to show that, with the right methodology, NGS can be transferred to the clinical practice, boosting the yield of SNHL genetic diagnosis to 50-60% (including GJB2/GJB6 alterations), improving diagnostic/prognostic accuracy, refining genetic and reproductive counseling and revealing clinically relevant undiagnosed syndromes.

Genomic profiling of intestinal-type sinonasal adenocarcinoma reveals subgroups of patients with distinct clinical outcomes.

BACKGROUND: Patients with intestinal-type sinonasal adenocarcinoma (ITAC) have an unfavorable prognosis and new therapeutic approaches are needed to improve clinical management. METHODS: Genetic analysis of 96 ITACs was performed by microarray comparative genomic hybridization and immunohistochemistry and correlated to previously obtained mutation, methylation, and protein expression data, and with pathological characteristics and clinical outcome. RESULTS: Seven copy number alterations (CNAs) were significantly associated with unfavorable clinical outcome: gains at 1q22-23, 3q28-29, 6p22, and 13q31-33, and losses at 4p15-16, 4q32-35, and 10q24. Unsupervised cluster analysis resulted in 5 subgroups of ITAC with significantly distinct genetic signatures and clinical outcomes, independently of disease stage or histological subtype. CONCLUSION: These data may guide studies to identify driver genes and signaling pathways involved in ITAC. In addition, the subclassification of genetic subgroups of patients with distinct clinical behavior can aid therapeutic decision making and may ultimately lead to personalized therapy with targeted inhibitors.

Tumores primarios del espacio parafaríngeo / Parapharyngeal space primary tumours

Introducción y objetivos: El objetivo de este estudio es presentar nuestra experiencia en el diagnóstico y tratamiento de los tumores parafaríngeos. Pacientes y método: Realizamos un estudio retrospectivo de 90 pacientes, diagnosticados y tratados quirúrgicamente de una tumoración parafaríngea entre 1984 y 2015. Fueron excluidos los pacientes cuyos tumores no eran primarios, sino que invadían esta región por contigüidad, los tumores originados en el lóbulo profundo de la parótida y las metástasis de otros tumores de cabeza y cuello. Resultados: El 74% de las neoplasias del espacio parafaríngeo fueron de naturaleza benigna y el 26% maligna. Los adenomas pleomorfos fueron los tumores más frecuentes (27%), seguido por los paragangliomas (25%), un grupo de tumores de origen misceláneo de naturaleza maligna (16%), los tumores de origen neurogénico (12%), un grupo de tumores de origen misceláneo de naturaleza benigna (10%) y los tumores malignos de glándulas salivales (10%). El tratamiento fue quirúrgico en todos los casos. Se realizó un abordaje transcervical en 56 pacientes, un abordaje cervical-transparotídeo en 15 pacientes, un abordaje infratemporal tipo A en 13 pacientes, un abordaje transmandibular en 4 pacientes y en 2 casos un abordaje transoral. Las complicaciones más frecuentes fueron las derivadas de lesiones de estructuras nerviosas. Conclusiones: La mayoría de los tumores localizados en el espacio parafaríngeo son subsidiarios de ser tratados de forma quirúrgica con una baja tasa de complicaciones y recurrencias. El abordaje transcervical es el más utilizado (AU)

Introduction and objectives: The aim of this study is to present our experience with the diagnostic and therapeutic approaches for parapharyngeal space tumours. Patients and method: This study is a retrospective review of 90 patients diagnosed with tumours of the parapharyngeal space and treated surgically between 1984 and 2015. Patients whose tumours were not primary but invaded the parapharyngeal space expanding from another region, tumours originating in the deep lobe of the parotid gland and head and neck metastasis were excluded from this study. Results: 74% percent of the parapharyngeal space neoplasms were benign and 26% were malignant. Pleomorphic adenoma was the most common neoplasm (27%), followed by paragangliomas (25%), miscellaneous malignant tumours (16%), neurogenic tumours (12%), miscellaneous benign tumours (10%), and malignant salivary gland tumours (10%). The transcervical approach was used in 56 cases, cervical-transparotid approach in 15 cases, type A infratemporal fossa approach in 13 cases, transmandibular approach in 4 cases and transoral approach in 2 cases. The most common complications were those deriving from nervous injuries. Conclusions: Most parapharyngeal space tumours can be removed surgically with a low rate of complications and recurrence. The transcervical approach is the most frequently used (AU)

Ausencia de translocaciones cromosómicas y de expresión proteica de ALK en los adenocarcinomas nasosinusales / Absence of chromosomal translocations and protein expression of ALK in sinonasal adenocarcinomas

Introducción. Las translocaciones de la región cromosómica 2p23 causan la sobreexpresión del gen de la quinasa del linfoma anaplásico (ALK), un receptor tirosinquinasa involucrado en rutas de señalización celular que regulan la proliferación. Dicha alteración se identifica en el 5% de los adenocarcinomas de pulmón, representando una diana terapéutica en dicho subgrupo de tumores. Debido a que los adenocarcinomas nasosinusales (ACNS) tienen una histología similar a los adenocarcinomas de pulmón, el objetivo de este estudio fue evaluar si existen alteraciones en el gen ALK en los ACNS. Método. La presencia de translocaciones del gen ALK se analizó en 96 muestras de ACNS mediante fluorescence in situ hybridization usando unas sondas «break apart». Además se estudió la expresión proteica de ALK por inmunohistoquímica. Resultados. En ninguno de los casos se observó la presencia de translocaciones de ALK. Además, no se detectó expresión proteica en ninguno de los casos. Conclusiones. Los resultados obtenidos sugieren que ALK no desempeña un papel relevante en la oncogénesis de los ACNS (AU)

Introduction. Chromosomal translocations at 2p23 cause overexpression of anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase involved in signalling pathways that regulate cell proliferation. This translocation occurs in 5% of lung adenocarcinoma and has been demonstrated to be useful as a therapeutic target for crizotinib. sinonasal adenocarcinomas (SNAC) are histologically similar to lung adenocarcinomas; the aim of this study was to evaluate the presence of ALK alterations in SNAC. Method. Break-apart fluorescent in-situ hybridization was used to analyse the presence of ALK translocations in 96 tumour samples. In addition, ALK protein expression was studied by immunohistochemistry. Results. The samples of SNAC did not show ALK translocation. Moreover, ALK protein expression was absent in all cases. Conclusions. These results suggest that ALK is not involved in SNAC (AU)

Seudotumor inflamatorio orbitario IgG4 asociado a aplasia etmoido-maxilar unilateral / IgG4 orbital inflammatory pseudotumor associated to unilateral ethmoid and maxillary sinus aplasia

No disponible

Absence of chromosomal translocations and protein expression of ALK in sinonasal adenocarcinomas. / Ausencia de translocaciones cromosómicas y de expresión proteica de ALK en los adenocarcinomas nasosinusales.

INTRODUCTION: Chromosomal translocations at 2p23 cause overexpression of anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase involved in signalling pathways that regulate cell proliferation. This translocation occurs in 5% of lung adenocarcinoma and has been demonstrated to be useful as a therapeutic target for crizotinib. sinonasal adenocarcinomas (SNAC) are histologically similar to lung adenocarcinomas; the aim of this study was to evaluate the presence of ALK alterations in SNAC. METHOD: Break-apart fluorescent in-situ hybridization was used to analyse the presence of ALK translocations in 96 tumour samples. In addition, ALK protein expression was studied by immunohistochemistry. RESULTS: The samples of SNAC did not show ALK translocation. Moreover, ALK protein expression was absent in all cases. CONCLUSIONS: These results suggest that ALK is not involved in SNAC.

Parapharyngeal space primary tumours. / Tumores primarios del espacio parafaríngeo.

INTRODUCTION AND OBJECTIVES: The aim of this study is to present our experience with the diagnostic and therapeutic approaches for parapharyngeal space tumours. PATIENTS AND METHOD: This study is a retrospective review of 90 patients diagnosed with tumours of the parapharyngeal space and treated surgically between 1984 and 2015. Patients whose tumours were not primary but invaded the parapharyngeal space expanding from another region, tumours originating in the deep lobe of the parotid gland and head and neck metastasis were excluded from this study. RESULTS: 74% percent of the parapharyngeal space neoplasms were benign and 26% were malignant. Pleomorphic adenoma was the most common neoplasm (27%), followed by paragangliomas (25%), miscellaneous malignant tumours (16%), neurogenic tumours (12%), miscellaneous benign tumours (10%), and malignant salivary gland tumours (10%). The transcervical approach was used in 56 cases, cervical-transparotid approach in 15 cases, type A infratemporal fossa approach in 13 cases, transmandibular approach in 4 cases and transoral approach in 2 cases. The most common complications were those deriving from nervous injuries. CONCLUSIONS: Most parapharyngeal space tumours can be removed surgically with a low rate of complications and recurrence. The transcervical approach is the most frequently used.

Gene Methylation Profiling in Sinonasal Adenocarcinoma and Squamous Cell Carcinoma.

OBJECTIVE: To identify epigenetic events in intestinal-type sinonasal adenocarcinoma (ITAC) and sinonasal squamous cell carcinoma (SNSCC) and to evaluate their relation to clinicopathologic features and follow-up data. STUDY DESIGN: Retrospective study. SETTING: Academic research hospital. SUBJECTS AND METHODS: The methylation status of 23 genes in 50 ITACs and 32 SNSCCs was analyzed by methylation-specific multiplex ligation-dependent probe amplification and its relation to clinicopathologic features and follow-up data. RESULTS: Gene methylation was observed in 50% of all tumors. Recurrent methylated genes in SNSCC were RASSF1 and CDH13 (for both, 6 of 32 cases), CHFR (4 of 32 cases), and TIMP3 (2 of 32 cases). None of these genes showed significant correlation to clinicopathologic features or overall survival. In ITAC, recurrent methylated genes were CDH13 (18 of 50 cases), ESR1 (13 of 50 cases), APC (7 of 50 cases), TIMP3 (5 of 50 cases), CASP8 (3 of 50 cases), and HIC1 and RASSF1 (for both, 2 of 50 cases). Papillary and colonic ITAC subtypes carried a mean of 1.26 gene methylations per tumor versus 0.63 in solid and mucinous subtypes. Methylation of TIMP3 was associated with a significantly worse survival in ITAC patients. CONCLUSION: ITAC carries a higher number and a different profile of gene methylations as compared with SNSCC. Gene methylation plays a greater role in papillary and colonic ITAC subtypes, which may indicate a different tumorigenic pathway for these ITAC subtypes. These findings could be used as prognosticators and may have implications for future individualized therapies based on epigenetic changes.

Integration of HIV infant testing into immunization programmes: a systematic review.

BACKGROUND: Integration of HIV infant testing into immunization sessions is one of the strategies designed to increase coverage of early infant diagnosis. OBJECTIVE: To determine the evidence on the outcomes of such integration. METHODS: A systematic review of peer-reviewed and grey literature was undertaken from electronic sources such as MEDLINE, Google Scholar, websites of international agencies, past conferences and ministries of health reports published between year 2002 and 2013. Randomized controlled trials, observational and qualitative studies were searched and those meeting selection criteria were selected and relevant information extracted using structured tool. Statistical pooling was not possible owing to the heterogeneity of the study designs and outcome measures. RESULTS: Of the nine articles which met the selection criteria, none used a randomized controlled design. Of these, five articles measured mother's acceptability of their infants being tested for HIV during its first pentavalent or DPT vaccination visit, and 89·5-100% accepted. Four articles reported the proportion of mothers who returned for HIV test results, ranging from 56·8% to 86·0%. Increased uptake of HIV testing following integration was confirmed by two articles. Only one study in Tanzania determined the uptake of vaccinations following integration, with urban facilities showing stable or slight increase of monthly vaccine uptake while decreases were observed across the rural sites. In two articles, stigma was perceived by service-providers and mothers as the potential risk following integration, particularly in rural settings. DISCUSSION: Despite the limited number of articles, the findings in this systematic review suggest that HIV testing during immunization clinic visits is acceptable and feasible as a possible model for service delivery. However, the impact on vaccination uptake needs further study.

Establishment and characterization of an orthotopic sinonasal squamous cell carcinoma mouse model.

BACKGROUND: Despite therapeutic improvements, patients with sinonasal squamous cell carcinoma (SCC) still face an unfavorable prognosis and there is great need for alternative treatments. METHODS: SCCNC4 cells, originally derived from a T2N1M0 primary and untreated sinonasal SCC, were inoculated in the maxillary sinus of immunodeficient mice. Histology, invasive behavior, and genetic features were evaluated and compared with the original primary tumor. RESULTS: The mice developed tumors that invaded bone, surrounding tissues, and brain, showing the same poor differentiation as the original primary tumor. Genetic analysis revealed an almost identical pattern of copy number alterations, except for the deletion and loss of expression of the genes CDKN2A and PTEN. CONCLUSION: This article shows the feasibility of an orthotopic mouse model of SCC of the maxillary sinus. Completed by genome-wide genetic profiling data, this model will be useful for preclinical testing of specific gene-targeted anticancer drugs.

Integration of HIV infant testing into immunization programmes: a systematic review.

Background: Integration of HIV infant testing into immunization sessions is one of the strategies designed to increase coverage of early infant diagnosis. Objective: To determine the evidence on the outcomes of such integration. Methods: A systematic review of peer-reviewed and grey literature was undertaken from electronic sources such as MEDLINE, Google Scholar, websites of international agencies, past conferences and ministries of health reports published between year 2002 and 2013. Randomized controlled trials, observational and qualitative studies were searched and those meeting selection criteria were selected and relevant information extracted using structured tool. Statistical pooling was not possible owing to the heterogeneity of the study designs and outcome measures. Results: Of the nine articles which met the selection criteria, none used a randomized controlled design. Of these, five articles measured mother's acceptability of their infants being tested for HIV during its first pentavalent or DPT vaccination visit, and 89·5-100% accepted. Four articles reported the proportion of mothers who returned for HIV test results, ranging from 56·8% to 86·0%. Increased uptake of HIV testing following integration was confirmed by two articles. Only one study in Tanzania determined the uptake of vaccinations following integration, with urban facilities showing stable or slight increase of monthly vaccine uptake while decreases were observed across the rural sites. In two articles, stigma was perceived by service-providers and mothers as the potential risk following integration, particularly in rural settings. Discussion: Despite the limited number of articles, the findings in this systematic review suggest that HIV testing during immunization clinic visits is acceptable and feasible as a possible model for service delivery. However, the impact on vaccination uptake needs further study.

Caracterización molecular de los carcinomas nasosinusales y sus implicaciones clínicas / Molecular characterisation of sinonasal carcinomas and their clinical implications

Los carcinomas nasosinusales son tumores infrecuentes, con mal pronóstico, y cuyo manejo es difícil y complejo, conllevando una elevada morbimortalidad, a pesar de los tratamientos quirúrgicos agresivos y la administración de radio y quimioterapia. Son tumores frecuentemente relacionados con la exposición profesional a carcinógenos. A diferencia de otros tumores de cabeza y cuello los estudios acerca de los cambios genético-moleculares de estos tumores son escasos. Esta revisión se centra en los hallazgos acerca de la epidemiología y la caracterización molecular y fenotípica de los carcinomas nasosinusales y, sus posibles implicaciones en el diagnóstico y tratamiento de los mismos. El progresivo conocimiento acerca de la biología molecular que subyace a su oncogénesis ayudaría a identificar las lesiones precursoras, los marcadores pronósticos y de respuesta a la quimiorradioterapia e identificar potenciales dianas moleculares que permitan ampliar las opciones terapéuticas (AU)

Sinonasal carcinomas are rare tumours with an unfavourable prognosis whose management is difficult and complex, leading to high morbidity and mortality despite improvements in the field of surgery and radiotherapy. An elevated number of these tumours can be attributed to occupational exposure. In comparison with other head and neck malignancies, studies of molecular changes in these tumours are infrequent. This review was focused on findings about the epidemiology and molecular and phenotypic characterisation of sinonasal carcinomas, which can potentially be useful for diagnosis and treatment. The increasing knowledge about the molecular biology that underlies their carcinogenesis may help to identify precursor lesions, prognostic markers and markers that predict chemoradiotherapy response and, finally, to identify potential molecular targets that will expand treatment options (AU)