Trastornos del habla en personas con esclerosis múltiple y su repercusión en la calidad de vida / Speech disorders in people with multiple sclerosis and its impact on the quality of life

Introducción: La esclerosis múltiple es una enfermedad desmielinizante de origen autoinmune que afecta al sistema nervioso central. Entre los daños que ocasiona se encuentran las alteraciones del habla, lo que compromete la capacidad comunicativa de las personas con esta enfermedad, disminuyendo así su calidad de vida. Objetivo: Analizar cómo influyen los trastornos de habla de las personas con esclerosis múltiple en las medidas de calidad de vida. Material y método: Participaron 45 personas con esclerosis múltiple, 14 (31.11%) con alteraciones del habla y 31 (68.88%) sin ellas. A todos se les pasó el Protocolo de Evaluación del Habla (PEH) y 2pruebas de calidad de vida (QoL-Dys y FAMS). Resultados: No se observaron diferencias en la calidad de vida general entre los participantes con y sin alteraciones del habla, pero sí en los ítems referidos a los índices de tristeza y depresión y en la prueba de calidad de vida específica respecto al habla. Conclusiones: Las personas con esclerosis múltiple muestran una reducción del tiempo máximo de fonación independientemente de que tengan o no disartria. Cuando esta está presente, la percepción que tienen sobre su calidad de vida se ve más afectada, especialmente respecto a las reacciones percibidas de terceras personas y a los índices de tristeza y depresión.(AU)

Introduction: Multiple sclerosis is a demyelinating disease of autoimmune origin that affects the central nervous system. Among the damages it causes are the alterations of speech, which compromises the communicative capacity of people with this disease, thus decreasing their quality of life. Objective: To analyze how speech disorders of people with multiple sclerosis influence quality of life measures. Material and method: 45 people with multiple sclerosis participated, 31 (68.88%) with no speech alterations and 31 (68,88%) with them. A speech assessment protocol (PEH), and 2quality of life test (QoL-Dys and FAMS) were applied to all the participants. Results: There are no differences in the general quality of life between participants with and without speech alterations, but there are differences in the items related to the rates of sadness and depression; and in the specific quality of life test regarding speech. Conclusions: People with multiple sclerosis show a reduction in maximum phonation time regardless of whether or not they have dysarthria. When this is present, their perception of their quality of life is more affected, especially with regard to the perceived reactions and the levels of sadness and depression.(AU)

Oncological and functional outcomes of transoral laser surgery for hypopharyngeal carcinoma.

BACKGROUND: Surgical resection or radiotherapy (RT) are standard approaches for early-staged hypopharyngeal squamous cell carcinoma (HPSCC). Transoral laser microsurgery (TOLMS) seems to provide good oncological and functional results with few local complications. The aim of our study was to analyze the outcomes of TOLMS, with or without neck dissection or RT, in the treatment of HPSCC in a tertiary referral center. METHODS: A retrospective study was conducted in patients with early T-category (T1-T2) HPSCC treated by TOLMS. RESULTS: A total of 34 patients were included in the study. The series includes 17 (50%) T1 and 17 (50%) T2 classified tumors. The 5-year overall survival and disease-specific survival rates were 51% and 66%, respectively, with a 5-year local control rate of 92%. All patients reassumed oral diet and none of them had a tracheostomy at the end of the follow-up. CONCLUSIONS: TOLMS offers an effective treatment option in terms of oncologic control and function preservation in locally circumscribed HPSCC.

Voice outcomes in patients with advanced laryngeal and hypopharyngeal cancer treated with chemo-radiotherapy.

Objective: Patients with locally advanced laryngeal and hypopharyngeal cancer (LHC) are often treated with chemo-radiotherapy to avoid total laryngectomy, although voice problems may occur even if not markedly manifest. We sought to evaluate the impact of chemoradiation on voice and quality of life. Methods: We studied 21 patients with locally advanced LHC with tumour control at least two years after chemo-radiotherapy. None manifested clinical symptoms related to the treatment and maintained an activity considered as within normal limits. All patients had a voice handicap index (VHI) of less than 15. Voice function was evaluated by perceptual vocal analysis (CAPE-V) and aerodynamic and acoustic study. Quality of life was assessed with the EORTC-H&N35 (voice items 46, 53 and 54). Results: Voice changes were frequent, with alterations in all CAPE-V attributes, and predominantly type II and III spectrograms in acoustic analysis (78%). The EORTC-H&N35 scale showed a reduction in scores in 10-40% of items related to voice. Conclusions: Subclinical voice disorders are common after chemo-radiotherapy. Although patients consider vocal impairment to be very minor and to not interfere with their daily life, it may contribute to a reduced quality of life.

Validation of "Self-Evaluation of Communication Experiences after Laryngectomy" (SECEL) Questionnaire for Spanish-Speaking Laryngectomized Patients.

BACKGROUND: Laryngectomized patients have communicative limitations when they lose their phonatory function after surgery. The scale "Self-Evaluation of Communication Experiences after Laryngectomy" (SECEL) assesses the impact of total laryngectomy on quality of life related to communication. The aim of this study was to translate and adapt the SECEL from English to Spanish and to apply this first version to a group of patients to check its reliability and validity. MATERIALS AND METHODS: One-hundred-and-one laryngectomized patients completed the SECEL scale adjusted to Spanish, the Voice Handicap Index (VHI-30), the Hospital Anxiety and Depression Scale (HADS) and the EORTC QLQ-H&N35 questionnaire. RESULTS: The Spanish version of the SECEL questionnaire has the same format and conceptual, semantic and idiomatic meaning as the original. The resulting model is composed of 21 items dimensioned in two highly correlated factors that are clear, meaningful, and replicable leading to measures that are reliable enough to be used in clinical evaluation. CONCLUSION: The Spanish translation and validation of the SECEL questionnaire were performed. It can be considered an appropriate tool to assess communication skills from laryngectomized people.

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.

Asymptomatic swallowing disorders may be present in individuals with laryngeal and hypopharyngeal cancer treated with chemo-radiotherapy.

PURPOSE: Patients with advanced laryngeal and hypopharyngeal cancer are often treated with chemo-radiotherapy to avoid total laryngectomy. Subclinical swallowing disorders could be present in these patients even though patients do not complain of any symptoms. We sought to evaluate the impact of chemoradiation on swallowing and quality of life. METHODS: We studied 21 patients undergoing chemo-radiotherapy for advanced laryngeal and hypopharyngeal cancer. All patients were tumor-free and none reported symptoms related to dysphagia during follow-up or showed altered routine screening tests (EAT-10) to detect it. Swallowing functions were assessed using volume-viscosity swallow test (V-VST) and fiberoptic endoscopic evaluation of swallowing (FEES). Quality of life was assessed with the EORT-H&N35, and SWAL-QOL scales. RESULTS: Frequent alterations in swallowing efficacy (100%) and safety (85.5%) were detected with V-VST and FEES. Quality-of-life scales showed a reduction in their scores between 12 and 17%, mainly in the areas of symptoms. CONCLUSION: Swallowing disorders are common after chemo-radiotherapy, even in patients who do not clinically manifest these disorders, contributing to a decrease in patients' quality of life. FEES and V-VST are useful procedures to detect asymptomatic swallowing disorders.

Aberrant Signaling Pathways in Sinonasal Intestinal-Type Adenocarcinoma.

Sinonasal intestinal-type adenocarcinoma (ITAC) is strongly related to occupational exposure to wood and leather dust, however, little is known on the genetic alterations involved in tumor development and progression. The aim of this study was to identify tumorigenic signaling pathways affected by gene mutations and their relation to clinical features. We applied whole exome sequencing of 120 cancer-related genes in 50 ITACs and analyzed the signaling activity of four specific pathways frequently affected by mutations. Genes involved in DNA damage response showed somatic mutations in 30% of cases, including four tumors that also harbored germline mutations. Genes in Wnt, MAPK and PI3K pathways harbored mutations in 20%, 20% and 24% of cases, respectively. Mutations and copy number gains in receptor tyrosine kinases possibly affecting MAPK and PI3K pathways occurred in 44% of cases. Expression of key pathway proteins showed no correlation to mutations in these pathways, except for nuclear ß-catenin and APC/CTNNB1 mutation. No specific gene mutation, mutated pathway, nor pathway activity level showed correlation to clinical data or survival. In addition, a similar mutational profile was observed among histological subtypes. The wide spectrum of gene mutations suggests that ITAC is a genetically heterogeneous without specific characterizing gene mutations.

Prognostic and Therapeutic Implications of Immune Classification by CD8+ Tumor-Infiltrating Lymphocytes and PD-L1 Expression in Sinonasal Squamous Cell Carcinoma.

Sinonasal squamous cell carcinoma (SNSCC) is an aggressive tumor predominantly arising in the maxillary sinus and nasal cavities. Advances in imaging, surgical and radiotherapeutic techniques have reduced complications and morbidity; however, the prognosis generally remains poor, with an overall 5-year survival rate of 30-50%. As immunotherapy may be a new therapeutic option, we analyzed CD8+ tumor-infiltrating lymphocytes (TILs) and the tumor microenvironment immune type (TMIT, combining CD8+ TILs and PD-L1) in a series of 57 SNSCCs. Using immunohistochemistry, tissue samples of 57 SNSCCs were analyzed for expression of CD8 on TILs and of PD-L1 on tumor cells. The results were correlated to the clinical and survival data. In total, 88% (50/57) of the tumors had intratumoral CD8+ TILs; 19% (11/57)-CD8high (>10%); and 39/57 (68%)-CD8low (1-10%). PD-L1 positivity (>5%) was observed in 46% (26/57) of the SNSCCs and significantly co-occurred with CD8+ TILs (p = 0.000). Using univariate analysis, high intratumoral CD8+ TILs and TMIT I (CD8high/PD-L1pos) correlated with a worse survival rate. These results indicate that SNSCCs are immunogenic tumors, similar to head and neck squamous cell carcinomas. Nineteen percent of the cases were both CD8high and PD-L1pos and this subgroup may benefit from therapy with immune checkpoint inhibitors.

Matched-Pair Analysis of Survival in the Patients with Advanced Laryngeal and Hypopharyngeal Squamous Cell Carcinoma Treated with Induction Chemotherapy Plus Chemo-Radiation or Total Laryngectomy.

BACKGROUND: We performed a comparative analysis between an organ-preservation protocol and surgery followed by radiotherapy in patients with locally advanced squamous cell carcinoma of the larynx and hypopharynx; Methods: 60 previously untreated patients who were treated with induction chemotherapy followed by chemoradiotherapy in responders were compared with a control group of 60 patients treated with up-front surgery. Both groups were statistically comparable, according to the subsite, TNM (tumor-node-metastasis) stage, age, and sex; Results: Mean age was 58 years and 92% were male. No significant statistical difference was observed for overall survival (OS) (HR 0.75; 95% CI 0.48-1.18; P = 0.22) and disease-specific survival (DSS) (HR 0.98; 95% CI 0.52-1.83, P = 0.96). Also, there was no significant difference for recurrence-free survival (HR 0.931; 95% CI 0.57-1.71; P = 0.81), metastases-free survival (HR 2.23; 95% CI 0.67-7.41; P = 0.19), and the appearance of second primary tumors (HR 1.22; 95% CI 0.51-2.88; P = 0.64); Conclusions: The results of the organ-preservation approach did not appear inferior to those of surgery plus (chemo)radiotherapy for patients with T3/T4a larynx and T2-T4a hypopharynx cancer with respect to OS and DSS, locoregional control and metastases-free survival.

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.

Lectin-Like Transcript 1 (LLT1) Checkpoint: A Novel Independent Prognostic Factor in HPV-Negative Oropharyngeal Squamous Cell Carcinoma.

Lectin-like transcript 1 (LLT1) expression by tumor cells contributes to immune evasion, thereby emerging as a natural killer (NK) cell-mediated immunotherapeutic target. This study is the first to investigate LLT1 expression (encoded by CLEC2D gene) in head and neck cancers to ascertain its impact on patient prognosis. LLT1 expression was analyzed by immunohistochemistry in a homogeneous cohort of human papillomavirus (HPV)-negative oropharyngeal squamous cell carcinomas (OPSCC), and correlated with clinical data. Results were further validated using transcriptomic data from the TCGA database. Tumoral LLT1 expression was detected in 190/221 (86%) OPSCC specimens, whereas normal pharyngeal epithelium was negative. Patients harboring LLT1-positive tumors showed significantly lower disease-specific (DSS) and overall survival (OS) (p = 0.049 and p = 0.036, respectively, log-rank test). High density of LLT1-positive tumor-infiltrating lymphocytes (TIL) was also frequently detected in 160 (73%) OPSCC samples, and significantly associated with better DSS and OS (p < 0.001 and p = 0.007, respectively). Multivariate Cox analysis further revealed that tumoral LLT1 expression and infiltration of LLT1-positive TIL were independent prognostic factors for DSS and OS. CLEC2D mRNA levels are also significantly increased in primary tumors compared to normal tissue. Strikingly, the prognostic impact of CLEC2D mRNA levels varied depending on HPV status in OPSCC, and among distinct cancer types. CLEC2D expression was significantly correlated with NK cell infiltration using the MCP-counter model. These findings uncover LLT1/CLEC2D as an independent prognostic factor in HPV-negative OPSCC, and a potential novel target for immunotherapy.

Espesantes comerciales clásicos y de nueva generación. Cualidades organolépticas y utilidad en las pruebas diagnósticas de la disfagia / Classic and new-generation commercial thickeners. Organoleptic qualities and usefulness in the diagnostic tests of dysphagia

INTRODUCCIÓN: los espesantes son muy utilizados en los trastornos de la deglución, tanto para su diagnóstico como para conseguir una alimentación segura y eficaz. Recientemente se han comercializado en el mercado español productos compuestos por gomas con el fin de mejorar las cualidades organolépticas y físicas de los alimentos espesados. OBJETIVO: comparar agentes espesantes de ámbito clínico comercializados en España y verificar sus características organolépticas y físicas para ser utilizados en los procedimientos diagnósticos y en la alimentación del paciente con disfagia. MÉTODO: se valoraron las propiedades organolépticas (apariencia, color, olor, sabor y regusto) y físicas (solubilidad y estabilidad) de ocho espesantes (4 clásicos con almidón y 4 nuevos a base de gomas) en una muestra de 44 sujetos sanos. Además, se estudió su utilidad en las pruebas diagnósticas al mezclarlos con colorantes y contrastes hidrosolubles. RESULTADOS Y CONCLUSIONES: los espesantes de nueva generación, a base de gomas, obtienen en general mejores puntuaciones en sus cualidades físicas y organolépticas con respecto a los espesantes convencionales. Los espesantes con almidón son más adecuados en las pruebas diagnósticas, ya que los espesantes con gomas presentan algunas peculiaridades en las mezclas con colorantes y contrastes que deben ser tenidas en cuenta en dichas pruebas

INTRODUCTION: thickeners are widely used in swallowing disorders, both for diagnosis and to achieve a safe and effective diet. Recently, products composed of gums have been commercialized in the Spanish market in order to improve the organoleptic and physical qualities of thickened foods. OBJECTIVE: to compare thickening agents of clinical scope marketed in Spain, and to verify their organoleptic and physical characteristics, to be used in the diagnostic procedures and the feeding of patients with dysphagia. METHOD: the organoleptic (appearance, colour, smell, taste, aftertaste) and physical (solubility, stability) properties of eight thickeners (4 classic starch-based and 4 new gum-based) were assessed in a sample of 44 healthy subjects. In addition, their usefulness in diagnostic tests was studied by mixing them with dyes and water-soluble contrasts. RESULTS AND CONCLUSIONS: new-generation thickeners, based on gums, generally obtain better scores for their physical and organoleptic qualities than conventional thickeners. Starch thickeners are more suitable for diagnostic tests, as gum thickeners present some peculiarities in their mixtures with dyes and contrasts that must be taken into account in diagnostic tests

[Classic and new-generation commercial thickeners. Organoleptic qualities and usefulness in the diagnostic tests of dysphagia]. / Espesantes comerciales clásicos y de nueva generación. Cualidades organolépticas y utilidad en las pruebas diagnósticas de la disfagia.

INTRODUCTION: Introduction: thickeners are widely used in swallowing disorders, both for diagnosis and to achieve a safe and effective diet. Recently, products composed of gums have been commercialized in the Spanish market in order to improve the organoleptic and physical qualities of thickened foods. Objective: to compare thickening agents of clinical scope marketed in Spain, and to verify their organoleptic and physical characteristics, to be used in the diagnostic procedures and the feeding of patients with dysphagia. Method: the organoleptic (appearance, colour, smell, taste, aftertaste) and physical (solubility, stability) properties of eight thickeners (4 classic starch-based and 4 new gum-based) were assessed in a sample of 44 healthy subjects. In addition, their usefulness in diagnostic tests was studied by mixing them with dyes and water-soluble contrasts. Results and conclusions: new-generation thickeners, based on gums, generally obtain better scores for their physical and organoleptic qualities than conventional thickeners. Starch thickeners are more suitable for diagnostic tests, as gum thickeners present some peculiarities in their mixtures with dyes and contrasts that must be taken into account in diagnostic tests.

INTRODUCCIÓN: Introducción: los espesantes son muy utilizados en los trastornos de la deglución, tanto para su diagnóstico como para conseguir una alimentación segura y eficaz. Recientemente se han comercializado en el mercado español productos compuestos por gomas con el fin de mejorar las cualidades organolépticas y físicas de los alimentos espesados. Objetivo: comparar agentes espesantes de ámbito clínico comercializados en España y verificar sus características organolépticas y físicas para ser utilizados en los procedimientos diagnósticos y en la alimentación del paciente con disfagia. Método: se valoraron las propiedades organolépticas (apariencia, color, olor, sabor y regusto) y físicas (solubilidad y estabilidad) de ocho espesantes (4 clásicos con almidón y 4 nuevos a base de gomas) en una muestra de 44 sujetos sanos. Además, se estudió su utilidad en las pruebas diagnósticas al mezclarlos con colorantes y contrastes hidrosolubles. Resultados y conclusiones: los espesantes de nueva generación, a base de gomas, obtienen en general mejores puntuaciones en sus cualidades físicas y organolépticas con respecto a los espesantes convencionales. Los espesantes con almidón son más adecuados en las pruebas diagnósticas, ya que los espesantes con gomas presentan algunas peculiaridades en las mezclas con colorantes y contrastes que deben ser tenidas en cuenta en dichas pruebas.

Prognostic Significance of the Pluripotency Factors NANOG, SOX2, and OCT4 in Head and Neck Squamous Cell Carcinomas.

Cancer stem cells (CSCs) play major roles in tumor initiation, progression, and resistance to cancer therapy. Several CSC markers have been studied in head and neck squamous cell carcinomas (HNSCC), including the pluripotency factors NANOG, SOX2, and OCT4; however, their clinical significance is still unclear. NANOG, SOX2, and OCT4 expression was evaluated by immunochemistry in 348 surgically-treated HNSCC, and correlated with clinicopathological parameters and patient outcomes. mRNA expression was further analyzed in 530 The Cancer Genome Atlas (TCGA) HNSCC. NANOG protein expression was detected in 250 (72%) cases, more frequently in patients with lymph node metastasis (p = 0.003), and was an independent predictor of better survival in multivariate analysis. While OCT4 expression was undetectable, SOX2 expression was observed in 105 (30%) cases, and strongly correlated with NANOG expression. Combined expression of both proteins showed the highest survival rates, and double-negative cases the worst survival. Strikingly, the impact of NANOG and SOX2 on outcome varied depending on tumor site and lymph node infiltration, specifically showing prognostic significance in pharyngeal tumors. Correlation between NANOG and SOX2 at mRNA and protein was specifically observed in node positive (N+) patients, and consistently correlated with better survival rates. According to our findings, NANOG protein expression is frequent in HNSCC, thereby emerging as an independent predictor of better prognosis in pharyngeal tumors. Moreover, this study uncovers a differential impact of NANOG and SOX2 expression on HNSCC prognosis, depending on tumor site and lymph node infiltration, which could facilitate high-risk patient stratification.

Selective neck dissection in the treatment of head and neck squamous cell carcinoma patients with a clinically positive neck.

OBJECTIVE: To determine the effectiveness and outcomes of SND in the treatment of patients with squamous cell carcinoma of the head and neck (SCCHN) with clinically positive neck (cN+) at diagnosis. MATERIAL AND METHODS: We retrospectively reviewed 159 patients with SCCHN with cN+ at diagnosis, who underwent a SND with curative intent at a tertiary care academic teaching hospital in Spain. We registered patient and tumor characteristics, date and site of recurrences, together with the outcomes. Survival rates were calculated by the Kaplan-Meier method. The minimum follow-up was 18 months or till death. RESULTS: A total of 28 neck recurrences were found in the whole series but only 10 neck recurrences occurred in absence of local recurrence. The regional control in the neck in absence of local recurrence was observed in 94% of patients. The neck recurrence rates did not correlated with the pN classification (P = 0.49), the administration of postoperative radiotherapy (P = 0.49) or extranodal extension (P = 0.43). The 5-year regional recurrence-free survival rate was 80% and 92% if only isolated neck recurrences are considered. CONCLUSIONS: SND offers an effective and oncologically safe surgical procedure in selected patients with clinically positive metastatic nodes in the neck. Our findings suggest that in cN1 and cN2 tumors, SND could replace the modified radical neck dissection without compromising oncologic efficacy.

The Differential Impact of SRC Expression on the Prognosis of Patients with Head and Neck Squamous Cell Carcinoma.

Aberrant SRC expression and activation is frequently detected in multiple cancers, and hence, targeting SRC has emerged as a promising therapeutic strategy. Different SRC inhibitors have demonstrated potent anti-tumor activity in preclinical models, although they largely lack clinical efficacy as monotherapy in late-stage solid tumors, including head and neck squamous cell carcinomas (HNSCC). Adequate selection and stratification of patients who may respond to and benefit from anti-SRC therapies is therefore needed to guide clinical trials and treatment efficacy. This study investigates the prognostic significance of active SRC expression in a homogeneous cohort of 122 human papillomavirus (HPV)-negative, surgically treated HNSCC patients. Immunohistochemical evaluation of the active form of SRC by means of anti-SRC Clone 28 monoclonal antibody was specifically performed and subsequently correlated with clinical data. The expression of p-SRC (Tyr419), total SRC, and downstream SRC effectors was also analyzed. Our results uncovered striking differences in the prognostic relevance of SRC expression in HNSCC patients depending on the tumor site. Active SRC expression was found to significantly associate with advanced disease stages, presence of lymph node metastasis, and tumor recurrences in patients with laryngeal tumors, but not in the pharyngeal subgroup. Multivariate Cox analysis further revealed active SRC expression as an independent predictor of cancer-specific mortality in patients with laryngeal carcinomas. Concordantly, expression of p-SRC (Tyr419) and the SRC substrates focal adhesion kinase (FAK) and the Arf GTPase-activating protein ASAP1 also showed specific associations with poor prognosis in the larynx. These findings could have important implications in ongoing Src family kinase (SFK)-based clinical trials, as these new criteria could help to improve patient selection and develop biomarker-stratified trials.

Peculiaridades anatómicas que influyen en la voz erigmofónica / Anatomical peculiarities having an influence on esophageal voice

La laringectomía total ocasiona un cambio morfológico trascendente en el aparato vocal, que altera totalmente el mecanismo fisiológico de la voz. Objetivo: describir aspectos claves de la morfología del aparato vocal de las personas que utilizan la voz erigmofónica para su comunicación. Material y método: estudio prospectivo de 15 pacientes laringectomizados que utilizan voz erigmofónica en los que se aplicaron los test VHI-30, CAPE-V y una exploración clínica y endoscópica, destacando los aspectos morfológicos que podrían influir en la voz. Resultados: el VHI-30 revela que perciben su voz como limitación leve y moderada. El CAPE-V indica una afectación media y grave. El VHI-30 (grados leve y moderado) se relaciona significativamente con la severidad global del CAPE-V. En la exploración clínica de la cavidad oral y el traqueostoma no se observan alteraciones que se relacionen con la valoración del CAPE-V. La exploración endoscópica muestra tendencias entre volúmenes y áreas de la cavidad faríngea y del esófago con el CAPE-V, pero sin llegar a valores significativos. Las formas de botón y diafragma del segmento faringoesofágico exhiben una tendencia similar. Conclusiones: la calidad de la voz erigmofónica percibida por el explorador dependería, en cierta medida, de las características anatómicas del nuevo aparato vocal del laringectomizado

Total laryngectomy causes a morphological change in the vocal apparatus, which totally alters the physiological mechanism of the voice. Aim: the objective of this article is to describe key aspects of the vocal apparatus morphology of patients who use the esophageal voice to communicate. Material and method: prospective study of 15 patients with esophageal voice in which the VHI-30, CAPE-V and a clinical and endoscopic exploration were performed, highlighting the morphological aspects that could influence the voice. Results: the VHI-30 reveals that they perceive their voice as a mild and moderate limitation. The CAPE-V indicates a medium and severe affectation. Both tests are significantly related in the mild and severe grades of VHI with the global severity of CAPE-V. The clinical exploration of the oral cavity and tracheostoma doesn't show that its variables present a trend with CAPE-V. Endoscopic exploration shows trends in the relationship between volumes and areas of the pharyngeal cavity and esophagus with the CAPE-V, but without reaching significant values. The button and diaphragm shapes of the pharyngoesophageal segment exhibit the same tendency. Conclusions: the variables studied indicate that the quality of the esophageal voice would depend, to some extent, on the anatomical characteristics of the new laryngectomized vocal apparatus

Oncological and functional outcomes of transoral laser surgery for laryngeal carcinoma.

INTRODUCTION: Transoral laser microsurgery (TLM) has become the standard approach for treatment of early-stage laryngeal carcinoma in most institutions due to their good oncological and functional results with few local complications. The purpose of this study was to analyze the oncological and functional results of TLM in the treatment of laryngeal tumors at our Hospital. MATERIALS AND METHODS: Patients with laryngeal squamous cell carcinoma (LSCC) treated from 1998 to 2013 with TLM with curative intention, and with a minimum follow-up of 24 months, were reviewed. RESULTS: 203 patients with LSCC were included. 195 patients were men (96%) and 8 women (4%), with a mean age of 63 years. The series includes 134 (66%) T1, 40 (20%) T2, and 29 (14%) T3-classified tumors. 116 tumors (57%) were in the glottis, 79 (39%) in the supraglottis and 8 (4%) in the anterior commissure. 16 patients (8%) received adjuvant radiotherapy. Initial local control was obtained in 75.5% of patients. The 5-year overall survival rate was 84% and the 5-year disease-specific survival was 90%. The presence of nodal metastasis (p < 0.001) and the involvement of the surgical margins (p = 0.004) were associated with a lower disease-specific survival in the multivariate analysis. All but three patients with local control of the disease reassumed oral diet, and none were tracheostomy-dependent. The 5-year laryngeal preservation rate was 85%. CONCLUSIONS: TLM is a minimally invasive treatment for early and moderately-advanced laryngeal carcinomas, with good oncologic and functional outcomes, and few complications as well.

Resultados de la laringectomía total en carcinomas localmente avanzados de hipofaringe / Results of total laryngectomy as treatment for locally advanced hypopharyngeal cancer

Introducción y objetivos: La laringectomía total (LT), más eventual radioterapia, ha demostrado ser un tratamiento eficaz en los casos de cáncer de hipofaringe localmente avanzado. El objetivo de este trabajo es analizar los resultados oncológicos de este procedimiento en pacientes con cáncer de hipofaringe T3 y T4. Métodos: Se incluyeron 59 pacientes (33 pacientes con estadio T3 y 26 con estadio T4a) con carcinoma epidermoide primario de hipofaringe tratados mediante LT entre los años 1998 y 2012. Resultados: La edad media fue de 61 años, con predominio de varones (96,6%). Todos los pacientes excepto uno eran fumadores y el 96% consumía alcohol. Se realizó vaciamiento cervical funcional unilateral en 12 pacientes, radical unilateral en 11 pacientes, funcional bilateral en 20 pacientes y funcional más radical en 14. El 66% de los pacientes recibieron radioterapia postoperatoria. Un 81% de los pacientes presentaba metástasis ganglionares y de estos un 56% presentaba invasión extracapsular. Un 29% de los pacientes presentaron recidiva locorregional, un 17% desarrollaron metástasis a distancia y un 25% un segundo tumor primario. La supervivencia específica fue del 46% a los 5 años. Conclusiones: La LT ampliada a faringe (con eventual radioterapia complementaria) ofrece buenos resultados oncológicos en términos de control locorregional de la enfermedad y supervivencia en el cáncer de hipofaringe localmente avanzado, de modo que los protocolos de preservación de órgano deben alcanzar resultados oncológicos similares a los demostrados por la LT (AU)

Introduction and objectives: Total laryngectomy (TL), with eventual postoperative radiotherapy, has proven to be effective in treating cases of locally advanced hypopharyngeal cancer. The aim of this study was to analyse the oncological outcomes of this procedure in patients with hypopharyngeal cancer classified T3 and T4. Methods: We studied 59 patients (33 T3 and 26 T4a) with primary squamous cell carcinoma of the hypopharynx treated with TL from 1998 to 2012. Results: Mean age was 61 years with a male predominance (96.6%). All the patients were smokers and 96% consumed alcohol. Unilateral selective neck dissection (ND) was performed in 12 patients, unilateral radical ND in 11 patients, bilateral selective ND in 20 patients and radical ND plus selective ND in 14 patients. 66% of the patients received postoperative radiotherapy. Lymph node metastases occurred in 81% of the patients and extranodal invasion in 56% of them. 29% of the patients had loco-regional recurrence, 17% developed distant metastases, and 25% a second primary tumour. The 5-year disease-specific survival was 46%. Conclusions: TL extended to pharynx (with eventual postoperative radiotherapy) offers good oncological results in terms of loco-regional control and survival in locally advanced hypopharyngeal cancer, so organ preservation protocols should achieve similar oncological results to those shown by TL (AU)