Sox2 and ßIII-Tubulin as Biomarkers of Drug Resistance in Poorly Differentiated Sinonasal Carcinomas.

Poorly differentiated sinonasal carcinomas (PDCs) are tumors that have a poor prognosis despite advances in classical treatment. Predictive and prognostic markers and new personalized treatments could improve the oncological outcomes of patients. In this study, we analyzed SOX2 and ßIII-tubulin as biomarkers that could have prognostic and therapeutic impacts on these tumors. The cohort included 57 cases of PDCs: 36 sinonasal undifferentiated carcinoma (SNUC) cases, 13 olfactory neuroblastoma (ONB) cases, and 8 sinonasal neuroendocrine carcinoma (SNEC) cases. Clinical follow-up data were available for 26 of these cases. Sox2 expression was detected using immunohistochemistry in 6 (75%) SNEC cases, 19 (53%) SNUC cases, and 6 (46%) ONB cases. The absence of Sox2 staining correlated with a higher rate of recurrence (p = 0.015), especially distant recurrence. The majority of cases showed ßIII-tubulin expression, with strong positivity in 85%, 75%, and 64% of SNEC, ONB, and SNUC cases, respectively. Tumors with stronger ßIII-tubulin expression demonstrated longer disease-free survival than those with no expression or low expression (p = 0.049). Sox2 and ßIII-tubulin expression is common in poorly differentiated sinonasal tumors and has prognostic and therapeutic utility.

Biomarkers for Immunotherapy in Poorly Differentiated Sinonasal Tumors.

The sinonasal cavities harbor a wide variety of rare cancer types. Histopathological classification can be challenging, especially for poorly differentiated tumors. Despite advances in surgery and radio-chemotherapy, the 5-year survival rate is still very low. Thus, there is an unmet clinical need for new therapeutic options. We retrospectively evaluated poorly differentiated tumors of 9 different histological subtypes from 69 patients who had received conventional treatments for the presence of CD8+ tumor-infiltrating lymphocytes (TILs), as well as the expression of PD-L1 and microsatellite instability (MSI) markers MLH1, MSH2, MSH6 and PMS2, as biomarkers for immunotherapy. CD8+ TILs were present in 23/69 (33%) cases, PD-L1 expression was observed in 23/69 (33%), and markers for MSI positivity in 5/69 (7%) cases. CD8+ TILs correlated with PD-L1 positivity, while both were mutually exclusive with MSI markers. None of the biomarkers were associated with clinical features as age, gender or tumor stage. Cases with CD8+ TILs and PD-L1 positivity showed a tendency toward worse disease-specific survival. Immune checkpoint inhibitors are emerging as new options for treatment of many tumor types. Our results indicate that also a substantial subset of patients with poorly differentiated sinonasal tumors may be a candidate to be treated with this promising new therapy.

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.

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.

Minimally invasive video-assisted parathyroidectomy (MIVAP) without intraoperative PTH determination.

BACKGROUND: Minimally invasive video-assisted parathyroidectomy (MIVAP) has become a standard approach to primary hyperparathyroidism (pHPT) since described. Although intraoperative parathyroid hormone assay (IOPTH) has been generalized as a complementary technique to MIVAP, its actual impact on the surgical success of this technique is not without controversy. The aim of this study was to describe our results in the management of pHPT with successful preoperative localization, by MIVAP technique, without IOPTH determination, confirming in a larger series our preliminary results. METHODS: A retrospective descriptive study was conducted in pHPT patients treated by MIVAP with no IOPTH determination in a tertiary hospital between 2007 and 2019. RESULTS: A total of 167 patients were included in the study. Biochemical cure was achieved in 96.4%, and 94.1% did not present any surgical complication. The mean duration of surgery was 61 min, and the mean length of hospital stay was 1.8 days CONCLUSIONS: In case of positive preoperative localization studies, MIVAP is a safe and effective technique for the surgical treatment of pHPT due to a parathyroid adenoma, regardless of IOPTH determination, with a success rate > 95% and a low complication rate.

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.

CD8+ Tumour-Infiltrating Lymphocytes and Tumour Microenvironment Immune Types as Biomarkers for Immunotherapy in Sinonasal Intestinal-Type Adenocarcinoma.

BACKGROUND: Intestinal-type adenocarcinoma (ITAC) is a rare tumour occurring in the ethmoid sinus. Recent years have brought advances in endoscopic surgery and precision radiotherapy; however, five-year overall survival has not improved and remains at 35-80%, depending on tumour stage and histology. Therefore, there is a need for new therapeutic options. METHODS: We evaluated CD8+ tumour-infiltrating lymphocytes (TILs) and tumour microenvironment immune type (TMIT, combining CD8+ TILs and PD-L1) as predictive biomarkers for immunotherapy in a series of 133 ITAC. All results were correlated to clinical and follow-up data. RESULTS: The presence of intratumoural CD8+ TILs was low in 57% of cases and high in 8% of cases. Tumoural PD-L1 positivity was observed in 26% of cases. CD8+ TILs and TMIT correlated with the histological subtype of ITAC and with better overall survival. The presence of stromal PD-L1-positive macrophages was related to intratumoural CD8+ TILs. PD-L1 expression on tumour cells or macrophages did not show prognostic value. CONCLUSIONS: TMIT classification did not have additional prognostic value over CD8+ TILs alone. The modest percentage of CD8high/PD-L1pos cases indicates that ITAC is a lowly immunogenic tumour type. Nevertheless, a proportion of ITAC, especially the papillary and colonic subtypes, could benefit from therapy with immune checkpoint inhibitors.

Translational genomics of sinonasal cancers.

The sinonasal cavities harbor a wide variety of histologically distinct cancers, the majority very aggressive with 5-year survival rates between 30-60% and local recurrence as the main cause of death. This is a complex anatomic area, close to structures such the eyes and the brain, which is of special relevance for surgery and postoperative radiotherapy. The low incidence of these rare tumors hampers accumulation of experience with diagnosis and clinical managment as well as knowledge on recurrent genetic aberrations or testing of new treatment strategies. However, recent years have seen a growing number of publications on genetic aberrations providing data that can aid or fine-tune classification and provide molecular targets for treatment with specific inhibitors. In addition, new sinonasal cancer models are created that enable preclinical testing of candidate inhibitor drugs. With more and more novel targeted therapies being developed, options for personalized treatment of sinonasal cancer patients are now opening up.

IDH2 Mutation Analysis in Undifferentiated and Poorly Differentiated Sinonasal Carcinomas for Diagnosis and Clinical Management.

A large number of tumor types arise from the mucosa of the sinonasal cavities. Although presenting clinically distinct behavior, due to poorly differentiated histologic features, they can be difficult to classify correctly. Our aim was to investigate whether IDH2 and IDH1 mutations may be specific to a subset of undifferentiated and poorly differentiated sinonasal carcinomas. A total of 125 tumor samples of 7 different histologic subtypes were analyzed for IDH mutations by sequencing and mutant-specific immunohistochemistry, and the results were correlated to clinical and follow-up data. The highest incidence of IDH2 mutations occurred in sinonasal undifferentiated carcinoma, with 11/36 (31%) cases affected. However, also, 1/9 neuroendocrine carcinomas, 2/4 high-grade non-intestinal-type adenocarcinomas, and 1/8 poorly differentiated squamous cell carcinomas carried the IDH2 mutation, whereas 1/48 intestinal-type adenocarcinomas harbored an IDH1 mutation. Immunohistochemical analysis of mutant IDH1/2 produced a number of false-negative results, but also 1 false-positive tumor was found. Disease-specific survival was more favorable in IDH2-mutant versus wild-type cases. Our data suggest that IDH-mutant sinonasal cancers, independent of their histologic subtype, may represent a distinct tumor entity with less aggressive clinical behavior. Clinically, patients with these mutations may benefit from specific IDH-guided therapies.

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.

Genetic profiling of poorly differentiated sinonasal tumours.

The sinonasal cavities harbour a variety of rare tumour types. Many carry a poor prognosis while therapeutic options are limited. Histopathological classification can be difficult, especially for poorly differentiated tumours such as olfactory neuroblastoma (ONB), sinonasal neuroendocrine carcinoma (SNEC) and sinonasal undifferentiated carcinoma (SNUC). We analysed Affymetrix OncoScan genome-wide copy number profiles of these three tumour types, both as originally diagnosed and as regrouped by their cytokeratin (Ck) and neuroendocrine (Ne) expression pattern, aiming to find a relation between phenotype and genotype. According to the original histopathological classification our series consisted of 24 ONB, 11 SNEC and 19 SNUC, while immunohistochemistry indicated 11 Ck-Ne+/ONB, 18 Ck+Ne+/SNEC, 24 Ck+Ne-/SNUC, and 1 Ck-Ne-/unclassified. As originally diagnosed, the three tumour types showed similar copy number profiles. However, when regrouped by Ck/Ne immunostaining we found a distinct set of gains and losses; Ck-Ne+/ONB harboured few and predominantly whole chromosomes abnormalities, Ck+Ne+/SNEC carried both gains and losses in high frequency, and Ck+Ne-/SNUC showed mostly gains. In addition, each tumour carried a number of unique chromosomal deletions. Genome-wide copy number profiling supports the value of immunohistochemical CkNe staining of ONB, SNEC and SNUC for tumour classification, which is important for prognosis and therapeutic decision-making.

Genome Comparison of Erythromycin Resistant Campylobacter from Turkeys Identifies Hosts and Pathways for Horizontal Spread of erm(B) Genes.

Pathogens in the genus Campylobacter are the most common cause of food-borne bacterial gastro-enteritis. Campylobacteriosis, caused principally by Campylobacter jejuni and Campylobacter coli, is transmitted to humans by food of animal origin, especially poultry. As for many pathogens, antimicrobial resistance in Campylobacter is increasing at an alarming rate. Erythromycin prescription is the treatment of choice for clinical cases requiring antimicrobial therapy but this is compromised by mobility of the erythromycin resistance gene erm(B) between strains. Here, we evaluate resistance to six antimicrobials in 170 Campylobacter isolates (133 C. coli and 37 C. jejuni) from turkeys. Erythromycin resistant isolates (n = 85; 81 C. coli and 4 C. jejuni) were screened for the presence of the erm(B) gene, that has not previously been identified in isolates from turkeys. The genomes of two positive C. coli isolates were sequenced and in both isolates the erm(B) gene clustered with resistance determinants against aminoglycosides plus tetracycline, including aad9, aadE, aph(2″)-IIIa, aph(3')-IIIa, and tet(O) genes. Comparative genomic analysis identified identical erm(B) sequences among Campylobacter from turkeys, Streptococcus suis from pigs and Enterococcus faecium and Clostridium difficile from humans. This is consistent with multiple horizontal transfer events among different bacterial species colonizing turkeys. This example highlights the potential for dissemination of antimicrobial resistance across bacterial species boundaries which may compromise their effectiveness in antimicrobial therapy.

Alterations of p14 ARF , p15 INK4b , and p16 INK4a Genes in Primary Laryngeal Squamous Cell Carcinoma.

The 9p21 gene cluster, harboring growth suppressive genes p14 ARF , p15 INK4b , and p16 INK4a , is one of the major aberration hotspots in head and neck cancers. We try to elucidate specific aberrations affecting this region, throughout methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) assay. Methylation of the gene was investigated by MS-MLPA in a well-characterized series of 27 laryngeal squamous cell carcinomas and 20 samples of healthy mucosa. Aberrant promoter hypermethylation was confirmed using and methylation-specific. All samples studied except 3 (11 %) presented losses at 9p21 segment. The most common finding was the small deletion (exon 1α) of the p16 INK4a locus (44 %). Deletion of the 9p21 gene cluster was identified in 5 cases (18 %). We only found methylation in 8 samples (30 %) for p15 IK4b -exon 1. Promoter methylation of p14 ARF , p15 IK4b and p16 INK4a was not detected in any tumor sample. Methylation-specific polymerase chain reaction confirmed the results. Our data indicate that there may be a subgroup of patients in which epigenetic regulation of 9p21 segment might have little relevance. Nevertheless, MS-MLPA could not be suitable for the study of methylation at this region and further research is required.

Cavernous sinus thrombosis during pregnancy.

Cavernous sinus thrombosis (CST) represents a rare but devastating disease process that may be associated with significant long-term patient morbidity or mortality. Rapid diagnosis and aggressive medical and surgical management are imperative for patients with CST. We present the case of a 24-year-old pregnant woman with intraorbital abscess and CST secondary to Streptococcus milleri. Surgical intervention included orbital abscess drainage and dental extraction, medical therapy included intravenous antibiotic, heparin, and methylprednisolone and an elective cesarean section was performed. The latter was the key point to resolution the disease.

Current management of sinonasal undifferentiated carcinoma.

BACKGROUND: The management of sinonasal undifferentiated carcinoma (SNUC) remains unclear. Low incidence and poor outcomes make treatment standardization difficult. The objective of this study was to review the used treatment and our outcomes. METHODS: From 2001 to 2013, 17 cases of SNUC were treated at our department. Charts were reviewed for standard demographic, tumour size and extension, histological features, treatment strategies, surgical approach, adjuvant therapies, outcomes and complications. RESULTS: All patients presented with extensive local disease and 2 patients also had neck metastases. All patients were treated using a multimodality approach: 10 patients underwent surgery and postoperative chemoradiation, 1 patient was treated with surgery and adjuvant radiotherapy, 3 patients were treated with neoadjuvant chemotherapy, surgery and postoperative chemoradiation and the remaining 3 patients were treated with chemoradiotherapy. After median follow-up of 39 months 6 patients developed recurrences. The 3-year local control rate was 76% and the 5-year rate of overall survival was 58%. CONCLUSIONS: Management and outcomes of SNUC have improved due to advances in surgery and radiotherapy. Gross tumour resection followed by postoperative radiotherapy should be the standard of care in patients with SNUC. High-precision high-dose radiotherapy should be implemented to try to improve the outcomes.

Resultados de la laringectomía total en carcinoma localmente avanzado de laringe en la era de la organopreservación / Results of total laryngectomy as treatment for locally advanced laryngeal cancer in the organ-preservation era

Introducción y objetivos: La laringectomía total (LT), más eventual radioterapia (RT), ha demostrado ser un tratamiento eficaz en los casos de cáncer de laringe localmente avanzado. El objetivo de este trabajo es analizar los resultados oncológicos de este procedimiento en pacientes con cáncer de laringe T3 y T4a. Métodos: Se incluyeron 80 pacientes (51 T3 y 29 T4a) con carcinoma epidermoide primario de laringe tratados mediante LT entre los años 1998 y 2006. Se realizó vaciamiento cervical bilateral en 54 pacientes, unilateral en 11 y central en 4. Veinte pacientes (25%) recibieron RT postoperatoria. Resultados: La edad media fue de 64 años, con predominio de varones (97%). El 96% eran fumadores y el 89% consumía alcohol. Un 44% de los pacientes presentaba metástasis ganglionares, y de estos un 37% mostró invasión extracapsular. En todos los casos se obtuvieron bordes libres de tumor. Un 25% de los pacientes presentaron recidiva locorregional y 5% desarrollaron metástasis a distancia. La supervivencia específica a 5 años fue de un 72% y la global del 55%. Las variables asociadas a menor supervivencia específica fueron la clasificación T4 (p = 0,068), la clasificación N2-N3 (p = 0,005), la invasión extracapsular (p = 0,018) y el estadio iv (p = 0,009). En el análisis multivariante la única variable significativa para la supervivencia específica fue la clasificación N2-N3 (p = 0,008). Conclusiones: La LT es un tratamiento eficaz para el manejo de los pacientes con cáncer de laringe localmente avanzado. Los protocolos de preservación de órgano deberían alcanzar resultados oncológicos similares a los demostrados por la LT (AU)

Introduction and objectives: Total laryngectomy (TL) and postoperative radiotherapy (RT), when indicated, have proven to be effective in treating cases of locally advanced laryngeal cancer. The aim of this study was to analyse the oncological outcomes of this procedure in patients with laryngeal cancer classified T3 and T4a. Methods: We studied 80 patients (51 T3 and 29 T4a) with primary squamous cell carcinoma of the larynx who underwent TL between 1998 and 2006. Bilateral neck dissection was performed in 54 patients, unilateral in 11, and central in 4. Twenty patients (25%) received postoperative radiotherapy. Results: Mean age was 64 years with a male predominance (97%). As for habits, 96% were smokers and 89% consumed alcohol. Lymph node metastases occurred in 44% of patients and extracapsular invasion in 37% of them. All cases had tumour-free margins. In all, 25% of patients had loco-regional recurrence and 5% developed distant metastases. The 5-year disease-specific survival was 72% and 5-year overall survival was 55%. Variables associated with decreased disease-specific survival were T4 classification (P = .068), N2-N3 classifications (P = .005), extracapsular invasion (P = .018) and stage iv disease (P = .009). On multivariate analysis, the only variable associated with decreased disease-specific survival was the presence of N2-N3 nodal metastases (P = .008). Conclusions: TL is an effective treatment for the management of patients with locally advanced laryngeal cancer. Organ preservation protocols should achieve similar oncological results to those obtained with TL (AU)

Resultados del tratamiento de los carcinomas epidermoides orofaríngeos mediante cirugía transoral / Outcomes following transoral resection of oropharyngeal squamous cell carcinoma

Introducción y objetivos: Los carcinomas de orofaringe son neoplasias agresivas habitualmente diagnosticadas en estadios avanzados. El objetivo de este estudio es exponer los resultados oncológicos y funcionales del tratamiento de estos tumores mediante resección quirúrgica transoral (RTO). Métodos: Se realizó un estudio retrospectivo en 43 pacientes con carcinoma epidermoide de orofaringe tratados mediante RTO. En el 52% de los casos el tumor se originaba en la región amigdalina, en el 23% en el paladar blando, en el 21% en la base de la lengua y en el 4% en la pared posterior. Ocho casos se clasificaron como estadio I, 9 como estadio II, 7 como estadio III, 16 como estadio IVA y 3 como estadio IVB. Dieciocho pacientes recibieron radioterapia postoperatoria. Se revisaron las historias de estos pacientes para obtener información en cuanto a control local y regional, supervivencia total y específica de la enfermedad, y función fonatoria y deglutoria. Resultados: La tasa global de recidivas fue del 44%, siendo la tasa de recidivas locales del 18%. La supervivencia global y específica a los 5 años fue del 55% y 66%, respectivamente. Las tasas de supervivencia específica a los 5 años según la localización tumoral fueron del 100%, 85%, 44%, y 30% para la pared posterior, amígdala, paladar blando y base de la lengua. El control local a los 5 años fue del 100%, 90%, y 0% para el paladar, amígdala y base de la lengua, respectivamente. En todos los casos se preservó la laringe, y los pacientes no requirieron traqueotomía definitiva y reanudaron la alimentación oral. Conclusiones: La RTO es una alternativa terapéutica eficaz para el tratamiento primario de los carcinomas de orofaringe, en la era de la quimio-radioterapia, obteniendo unos buenos resultados oncológicos y funcionales (AU)

Introduction and objectives: The aim of our study was to evaluate outcomes of a minimally invasive approach, using transoral surgery (TOS) as the primary treatment for oropharyngeal carcinoma. Methods: We reviewed 43 previously untreated patients with oropharyngeal carcinoma, who were treated with TOS. Distribution of the primary tumor site was: tonsil (52%), soft palate (23%), base of the tongue (21%) and posterior wall (4%). Eight patients had a stage I disease, 9 had a stage II disease, 7 had a stage III disease, 16 had a stage IVA, and 3 had stage IVB disease. Eighteen patients underwent postoperative radiotherapy. Records of these patients were reviewed to obtain measures such as local and regional control, overall and disease-specific survival, and speech and swallowing function. Results: The overall recurrence rate was 44%, and the local recurrence rate was 18%. The 5-year overall survival and disease-specific survival rates were 55% and 66%, respectively. Five-year disease-specific survival rates by site were as follows: 100%, 85%, 44%, and 30% for posterior wall, tonsil, soft palate and base of the tongue, respectively. Five-year estimates for local control were 100%, 90%, and 0% for palate, tonsil and for base of the tongue tumors, respectively. All of the patients preserved the larynx and live without tracheotomy and oral alimentation was successfully without feeding tube. Conclusions: TOS as the primary treatment approach offers a surgical alternative for treatment of the primary oropharyngeal tumor, in the era of chemoradiation therapy. This approach confers a good local control and functional outcomes (AU)

[Results of total laryngectomy as treatment for locally advanced laryngeal cancer in the organ-preservation era]. / Resultados de la laringectomía total en carcinoma localmente avanzado de laringe en la era de la organopreservación.

INTRODUCTION AND OBJECTIVES: Total laryngectomy (TL) and postoperative radiotherapy (RT), when indicated, have proven to be effective in treating cases of locally advanced laryngeal cancer. The aim of this study was to analyse the oncological outcomes of this procedure in patients with laryngeal cancer classified T3 and T4a. METHODS: We studied 80 patients (51 T3 and 29 T4a) with primary squamous cell carcinoma of the larynx who underwent TL between 1998 and 2006. Bilateral neck dissection was performed in 54 patients, unilateral in 11, and central in 4. Twenty patients (25%) received postoperative radiotherapy. RESULTS: Mean age was 64 years with a male predominance (97%). As for habits, 96% were smokers and 89% consumed alcohol. Lymph node metastases occurred in 44% of patients and extracapsular invasion in 37% of them. All cases had tumour-free margins. In all, 25% of patients had loco-regional recurrence and 5% developed distant metastases. The 5-year disease-specific survival was 72% and 5-year overall survival was 55%. Variables associated with decreased disease-specific survival were T4 classification (P=.068), N2-N3 classifications (P=.005), extracapsular invasion (P=.018) and stage iv disease (P=.009). On multivariate analysis, the only variable associated with decreased disease-specific survival was the presence of N2-N3 nodal metastases (P=.008). CONCLUSIONS: TL is an effective treatment for the management of patients with locally advanced laryngeal cancer. Organ preservation protocols should achieve similar oncological results to those obtained with TL.

DNA aneuploidy-specific therapy for head and neck squamous cell carcinoma.

BACKGROUND: Patients with head and neck squamous cell carcinoma (HNSCC) have an unfavorable prognosis, with a 5-year survival rate of approximately 40%. Genetic analyses have revealed that the majority of HNSCCs carry complex, aneuploid karyotypes, showing numerical and structural chromosomal imbalances. New compounds are being developed that target chromosomal instability in general, specifically affecting cells with aneuploid karyotypes. METHODS: Two such compounds, 5-aminoimidazole-4-carboxamide riboside (AICAR) and 17-allylamino-17-demethoxygeldanamycin (17-AAG), were tested using a panel of stable diploid and unstable aneuploid HNSCC cell lines, and short-term cultures of normal keratinocytes as control. RESULTS: A significant growth inhibitory effect by both compounds was observed in the aneuploid compared to diploid HNSCC cell lines and to the normal keratinocytes. This effect was independent from the TP53 mutation status. Combination treatment with AICAR and 17-AAG demonstrated the strongest inhibition. CONCLUSION: Aneuploidy-targeted therapy may be a viable addition to the treatment options for HNSCC.

[Outcomes following transoral resection of oropharyngeal squamous cell carcinoma]. / Resultados del tratamiento de los carcinomas epidermoides orofaríngeos mediante cirugía transoral.

INTRODUCTION AND OBJECTIVES: The aim of our study was to evaluate outcomes of a minimally invasive approach, using transoral surgery (TOS) as the primary treatment for oropharyngeal carcinoma. METHODS: We reviewed 43 previously untreated patients with oropharyngeal carcinoma, who were treated with TOS. Distribution of the primary tumor site was: tonsil (52%), soft palate (23%), base of the tongue (21%) and posterior wall (4%). Eight patients had a stage I disease, 9 had a stage II disease, 7 had a stage III disease, 16 had a stage IVA, and 3 had stage IVB disease. Eighteen patients underwent postoperative radiotherapy. Records of these patients were reviewed to obtain measures such as local and regional control, overall and disease-specific survival, and speech and swallowing function. RESULTS: The overall recurrence rate was 44%, and the local recurrence rate was 18%. The 5-year overall survival and disease-specific survival rates were 55% and 66%, respectively. Five-year disease-specific survival rates by site were as follows: 100%, 85%, 44%, and 30% for posterior wall, tonsil, soft palate and base of the tongue, respectively. Five-year estimates for local control were 100%, 90%, and 0% for palate, tonsil and for base of the tongue tumors, respectively. All of the patients preserved the larynx and live without tracheotomy and oral alimentation was successfully without feeding tube. CONCLUSIONS: TOS as the primary treatment approach offers a surgical alternative for treatment of the primary oropharyngeal tumor, in the era of chemoradiation therapy. This approach confers a good local control and functional outcomes.