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.

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.

Retropharyngeal abscess and mediastinitis as an uncommon complication of varicella infection.

Varicella infection is one of the most common and contagious infection in children and could course with severe complications. We report the case of a 4-year-old patient derived to our hospital for suspicion of suppurative complication in the context of a varicella infection. A computerized tomographic scanning was performed, showing a large retropharyngeal abscess with mediastinitis. Complications of varicella are up to 2% of patients, but this is the first report of a retropharyngeal and mediastinal abscess in this context. In the face of clinical suspicion, early intervention is important through imaging, intravenous antibiotics and surgical drainage in necessary cases.

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.

Predictive value of EGFR-PI3K-pAKT-mTOR-pS6 pathway in sinonasal squamous cell carcinomas. / Valor pronóstico de la ruta de EGFR-PI3K-pAKT-mTOR-pS6 en los carcinomas epidermoides nasosinusales.

BACKGROUND AND OBJECTIVES: We have previously indicated that EGFR has a role in carcinogenesis in a subgroup of sinonasal squamous cell carcinomas (SNSCC). In addition, EGFR activates 2 of the most important intracellular signalling pathways: PI3K/pAKT/mTOR/pS6 and MAP pathway kinases. The objective of this study was to evaluate the involvement of the EGFR/PI3K/pAKT/mTOR/pS6 pathway and its relationship with clinical-pathological parameters and follow-up of sinonasal squamous cell carcinoma. MATERIAL AND METHODS: The immunohistochemical expression of different components of the PI3K/AKT/mTOR/pS6 pathway and its relationship with various clinical-pathological parameters was studied in a series of 54 patients with SNSCC. RESULTS: Loss of PTEN expression was observed in 33/54 cases (61%) and pAKT, mTOR and pS6 pre-expression was observed in 19/54 cases (35%), 8/54 cases (15%), and 47/54 cases (87%), respectively. Loss of PTEN expression was related to intracranial invasion and development of regional metastases (p=0.005). Overexpression of pS6 was associated with a decrease in survival (p=0.008), presence of local recurrences (p=0.055), and worsening of overall prognosis (p=0.007). No significant relationships were observed between pAKT and mTOR expression and the clinicopathological parameters studied. CONCLUSIONS: Alterations in the expression of EGFR/PI3K/pAKT/mTOR/pS6 pathway components are common in a subgroup of SNSCC. This study reveals that the absence of pS6 overexpression is associated with better clinical outcomes. Therefore, pS6 expression could be considered as an unfavourable prognostic marker.

Management of differentiated thyroid carcinomas. / Manejo de los carcinomas diferenciados de tiroides.

INTRODUCTION AND OBJECTIVES: Radioiodine is the principal treatment for differentiated thyroid carcinomas. The aim of this study is to present our experience in the management of these tumours. MATERIAL AND METHOD: We present a retrospective study of 55 patients operated for differentiated thyroid carcinoma in our hospital between 2007 and 2011. RESULTS: The mean age at time of diagnosis was 49 years, and females predominated (78% of cases). Seventy eight percent of the patients were in the initial stages (stages i and ii). The definitive histopathological diagnosis was papillary carcinoma in 84% and follicular carcinoma in the remaining 16%. All of the patients, with the exception of 2 (4%), underwent total thyroidectomy, with lymphadenectomy in 58% of cases. Nine percent of the patients had permanent hypoparathyroidism and although 18% suffered transitory unilateral paralysis, 40% of these female patients had completely recovered after 6 months. Eighty-nine percent of the patients were given radioiodine postoperatively. There was a recurrence rate of 40% most of which was at cervical level (29% of the patients). Survival at 5 years was 87%, 95% of the papillary subtype, falling to 56% of the follicular subtype (P=.001). DISCUSSION/CONCLUSIONS: The prognosis for differentiated thyroid carcinomas is excellent after appropriate surgical treatment, thorough preoperative assessment,and strict postoperative follow-up due to the significant recurrence rates.

Management of severe and/or refractory epistaxis. / Manejo de las epistaxis graves y/o refractarias.

OBJECTIVE: The objective was to determine the results of the treatment of severe and/or refractory epistaxis requiring hospital admission. In addition, the results of arterial ligation versus embolization were compared. MATERIAL AND METHOD: Sixty-three patients with severe and/or refractory epistaxis requiring hospital admission between August 2014 and December 2016 were included prospectively. RESULTS: Eleven patients (17%) underwent embolization, 5 (8%) endoscopy ligation and the remaining 47 (75%) underwent conservative treatment with tamponade. The mean age of the patients in which conservative measures were sufficient was 72 years, while the age of those treated with embolization was 71 years and of those who underwent surgery was 53 years. For the patients who underwent conservative treatment or surgery, the average stay was 6 days, compared to 9 days for those who underwent embolization. One patient suffered a hemispheric stroke after embolization. No post-surgical complications were observed. CONCLUSIONS: Most cases of severe and/or refractory epistaxis are resolved by conventional tamponade. Endoscopy ligation is associated with a decrease in hospital stay, without serious complications. It is advisable to have all the possible therapeutic options available, for which the presence of interventional radiologists and experienced surgeons is essential to avoid complications and decide the treatment to be performed individually for each patient.

Validation of the measures of cepstral peak prominence as a measure of dysphonia severity in Spanish-speaking subjects. / Validez de las medidas del pico cepstral para la valoración objetiva de la disfonía en sujetos de habla hispana.

INTRODUCTION AND OBJECTIVES: Perceptual rating of overall voice quality and other more specific perceptual dimensions is difficult, as such judgments depend on the listener's subjectivity. Thus, finding objective, valid, and accessible clinical measures to include in comprehensive voice evaluation protocols is a priority. The purposes of this study were to 1) determine the diagnostic accuracy of a single acoustic measure, smoothed cepstral peak prominence (CPPS), to predict voice disorder status from sustained vowels and connected speech samples using the software Praat; 2) to determine the relationship between measures of CPPS and perceptual ratings of vocal quality; and 3) describe the normative values of CPPS. METHOD: Measures of CPPS were obtained from connected speech and sustained vowel recordings of 72 Spanish-speaking subjects with voice disorders and 52 nondysphonic Spanish-speaking subjects with no vocal disorders using freely downloadable Praat software. IBM SPSS Statistics software version 23 was used to complete the statistical analyses. RESULTS: results revealed a 70% sensitivity rate, a specificity rate of 85%. Estimated severity for sustained vowels and connected speech were strongly correlated and significantly associated with listener ratings of dysphonia severity. CONCLUSIONS: A single acoustic measure of CPPS was highly predictive of voice disorder status using Praat software. Clinicians may consider using CPPS to complement clinical voice evaluation and screening protocols.

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

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.

Treatment of the first bite syndrome. / Tratamiento con toxina botulínica del síndrome del primer mordisco.

First bite syndrome is a potential complication of surgery involving the infratemporal fossa, deep lobe of the parotid gland and parapharyngeal space. It is described as an acute and intense pain in the parotid region caused with the first bite of each meal. It is related to damage to sympathetic innervation of the parotid gland. Parasympathetic hyperactivation is believed to stimulate an exaggerated myoepithelial cell contraction causing pain. Usual analgesic treatments have poor results. Botulinum toxin type A causes parasympathetic nerve paralysis of the parotid gland and this fact would minimize salivation and decrease first bite syndrome. The aim of this study is to show the details of the technique and our outcomes in 5 patients treated with botulinum toxin type A.