CK2beta is expressed in endometrial carcinoma and has a role in apoptosis resistance and cell proliferation.

Protein kinase CK2 (CK2) is a serine/threonine kinase that participates in important cellular processes. We have recently demonstrated that CK2 plays a role in resistance to TRAIL/Fas-induced apoptosis in endometrial carcinoma (EC) by regulating FLIP. Here, we assessed the immunohistochemical expression of CK2beta in EC and checked its role in cell proliferation and anchorage-independent cell growth. CK2beta immunostaining was assessed in two tissue microarrays, one constructed from paraffin-embedded blocks of 95 ECs and another from 70 samples of normal endometrium. CK2beta expression was correlated with histological type; grade and stage; cell proliferation (Ki-67) and apoptotic index; immunostaining for cyclin D1, PTEN, AKT, beta-catenin, and FLIP. Moreover, the Ishikawa EC cell line was subjected to down-regulation of CK2 by shRNA. CK2beta expression was frequent in EC (nuclear, 100%; cytoplasmic, 87.5%). The staining was more intense in EC than in normal endometrium (P = 0.000), and statistically correlated with AKT, PTEN, beta-catenin, and FLIP. In EC, CK2beta expression correlated with cell proliferation. Knock-down of CK2beta blocked colony formation of EC in soft agar, and also resulted in decreased expression of cyclin D1 and ERK phosphorylation. The results confirm that CK2beta is widely expressed in EC, and suggest a role in cell proliferation and anchorage-independent cell growth.

[First-bite syndrome]. / El síndrome del primer mordisco.

First-bite syndrome consists of the appearance of pain in the parotid at the beginning of mastication, due to damage to the cervical sympathetic chain or the sympathetic plexus innervating the parotid gland. Clinical presentation in a patient who has undergone surgery of the parapharyngeal space suggests the diagnosis. We report here the case of a patient who presented first-bite syndrome after being operated on for a cervical sympathetic chain schwannoma.

[Clinical significance of unilateral tonsillar enlargement]. / Significación clínica de la asimetría amigdalina.

INTRODUCTION: Asymptomatic unilateral tonsillar enlargement is usually treated with systematic tonsillectomy under suspicion of malignancy. Due to the fact that most of the cases are benign pathologies, we set out to study the clinical signs that would help us in the diagnosis in order to avoid unnecessary tonsillectomies. MATERIAL AND METHODS: We reviewed 267 tonsillectomies performed from 1996 to 2006 and 30 of these were indicated because of asymmetry. We evaluated risk factors for malignancy: cervical lymphatic node enlargement, sex, age, tonsillar enlargement noticed by the patient, suspicious appearance, systemic symptoms, history of malignancy and immunocompromise. RESULTS: Histopathologic study revealed 80 % to be benign and 20 % malignant. The risk factors with the strongest association were enlargement of cervical lymphatic nodes and suspicious appearance of the tonsil. CONCLUSIONS: Strict control of a unilateral tonsillar enlargement is possible, but it is mandatory to perform a tonsillectomy when the appearance of the tonsil raises suspicions or there are enlarged lymphatic nodes.

[Pharyngocutaneous fistula following total laryngectomy. A case-control study of risk factors implicated in its onset]. / Fístula faringocutánea tras laringectomía total. Estudio de casos y controles de los factores de riesgo implicados en su aparición.

INTRODUCTION AND OBJECTIVES: Pharyngocutaneous fistula is the most frequent complication after total laryngectomy. Risk factors involved in its appearance have been studied by many authors without conclusive results. Our main objective is to identify the risk factors involved in the onset of fistulae at our institution. METHODS: A retrospective case-control study was designed. Thirty-three patients subjected to total laryngectomy with the same protocol were included in both groups. Patients who required a complex surgical reconstruction were excluded in order to avoid biases. RESULTS: The only risk factor with statistical significance (P=.04) for the onset of fistulae in our setting is the extension of the surgery to the pharynx (OR=2.83). The association of prior radiotherapy and concurrent neck dissection displayed a notable trend (OR=0.32) but without significance (P=.099). Patient age, prior radiotherapy, concurrent neck dissection, prior tracheotomy and post-operative haemoglobin level did not predispose to this complication in our study. Non-surgical closure of the pharyngocutaneous fistula was achieved in most cases (72.7 %) but patients who had pre-operative radiotherapy required surgical closure more frequently (P< .01) than those not irradiated. CONCLUSIONS: At our centre the main risk factor associated with post-laryngectomy fistulae is the extension of surgery to the pharynx. In previously-irradiated patients, fistulae have a lower incidence of non-surgical closure and require more aggressive surgery to resolve them.

[The silent sinus syndrome]. / Síndrome del seno silente.

The silent sinus syndrome is a very infrequent pathology. It is described as an enophthalmos secondary to collapse and opacification of maxillary sinus without presenting sinus or nasal symptoms. Osteomeatal complex obstruction is the triggering physiopathologic factor. The clinical symptoms and imaging findings lead to the diagnosis. The treatment consists in restoring sinus ventilation and, if necessary, correcting the orbital floor. We report a case of a woman who was diagnosed and treated because of this entity in our hospital.

Caloric and rotatory chair test results in patients with Ménière's disease.

OBJECTIVES: To determine whether an association exists between the parameters of the caloric and rotatory chair tests in patients with unilateral Ménière's disease. METHODS: Patients with unilateral Ménière's disease (n = 100) were subjected to the caloric and the rotatory chair test (sinusoidal harmonic acceleration and impulsive tests) on the same day. Canal paresis and directional preponderance were assessed in the caloric test, and different variables were measured in the rotatory chair test based on the existence of abnormal parameters in the vestibulo-ocular reflex at two or three consecutive frequencies of those tested and on the time constant of the vestibulo-ocular reflex. STUDY DESIGN AND SETTING: A prospective study was conducted at a University hospital. RESULTS: An abnormal result in the caloric test was obtained from 73% of the patients. In the rotatory chair test, the most frequent abnormal findings involved increases in the normal phase lead at 2 consecutive frequencies tested (23%). There was a stronger association between an abnormal result in phase, gain, and/or symmetry at three adjacent frequencies and a pathological result in the caloric test. CONCLUSION: Very few of the criteria used to define the caloric and rotatory chair tests seem to be associated. This confirms previous knowledge that both tests examine vestibulo-ocular reflex by different ways. Only when vestibular dysfunction is severe enough (manifested by the finding of an abnormal result in at least three consecutive frequencies in the rotatory chair test), the caloric test is also found to be abnormal.

Mutation analysis of the SDHD gene in four kindreds with familial paraganglioma: description of one novel germline mutation.

The familial paraganglioma syndrome is an autosomal dominant disorder characterized by the presence of carotid body paragangliomas and, less frequently, paragangliomas of the glomus jugulare, glomus vagale, and adrenal pheochromocytomas. Germline mutations of the genes for succinate dehydrogenase subunits D, B, or C (SDHD, SDHB, SDHC) have been identified in some kindreds with familial paraganglioma. In this study, we report the clinicopathologic features of four different kindreds with familial paraganglioma, which were screened for germline mutations in the SDHD gene. DNA was obtained from tumor and normal tissue, as well as from peripheral blood. Mutation analysis was performed by single-strand conformation polymorphism analysis and DNA sequencing. SDHD germline mutations were detected in the affected family members of the four families, as well as in several asymptomatic carriers. An identical mutation in exon 4 of SDHD (334-337delACTG) was identified in two apparently unrelated kindreds. The third family showed a germline mutation in exon 2 (W43X). The mutations present in these three families had been previously described in Spanish families, suggesting a founder effect. The fourth family exhibited a mutation in exon 2 of SDHD (170-171delTT), which had not been previously identified. The affected family members of the four kindreds showed paragangliomas, located in the head and neck region, and all of them were benign. These results confirm that genetic testing of SDHD may be a powerful tool for the identification of the syndrome in patients with multiple or bilateral paragangliomas.

DcR1 expression in endometrial carcinomas.

The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the TNF family, which mediates apoptosis by the extrinsic pathway. Up-regulation of decoy receptors, DcR1 and DcR2, may result in diminished binding of TRAIL to their functional receptors. DcR1 expression was assessed in normal endometrial tissue (NE) and endometrial carcinoma (EC) samples by immunohistochemistry (IHC) and quantitative real-time polymerase chain reaction (PCR). IHC was performed in two tissue microarrays; one composed of 80 samples of NE and a second one constructed from paraffin-embedded blocks of 62 EC. For quantitative real-time RT-PCR analysis, RNA was obtained from 19 NE and 28 EC samples using Trizol. mRNA expression of DcR1 was assessed with Taqman-based assays in an Abi-Prism 700 SDS. Results were correlated with stage, histological type, and grade. By IHC, cytoplasmic expression of DcR1 was frequently seen in NE (79.6%) and varied according to the menstrual cycle. Positive DcR1 immunostaining was also detected in EC (98.1% of the cases) without any specific statistical association with histological type, grade, and stage. By quantitative real-time PCR, all NE had similar levels of DcR1expression (0.8-1.7 RQ), which were considered the basal levels of DcR1 expression in NE. Increased DcR1 expression (> or =5-fold higher than the basal levels) was detected in 13 of 28 EC (46.4%). High DcR1 expression levels were found in ECs of different stages: IA, four of 12 (33%); IB, two of four (50%); IC, four of six (66%); and IIA and IIB three of six (50%). Results suggest that DcR1 expression occurs in a subset of EC and may contribute to resistance to TRAIL-induced apoptosis.

Promoter hypermethylation and reduced expression of RASSF1A are frequent molecular alterations of endometrial carcinoma.

Alterations in the regulation of the RAS-MAPK pathway are frequent in endometrial carcinoma. RASSF1A is a tumor-suppressor gene that can regulate this pathway negatively. RASSF1A has been found to be inactivated by promoter methylation in some human tumors. The aim of the study was to assess the immunohistochemical expression of RASSF1A in normal endometrium and endometrial carcinoma, and to correlate its expression with K-RAS mutations, presence of microsatellite instability, RASSF1A promoter methylation, and clinicopathological data. RASSF1A immunostaining was evaluated in one tissue microarray constructed from 80 paraffin-embedded samples of normal endometrium, and two tissue microarrays constructed with a total of 157 endometrial carcinomas (one constructed with 95 endometrial carcinomas previously evaluated for K-RAS mutations, and microsatellite instability, and another one containing 62 endometrial carcinomas that were also subjected to RASSF1A promoter methylation analysis). RASSF1A immunostaining was correlated with cell proliferation (Ki67), Cyclin D1 expression and clinicopathological data. Promoter methylation of RASSF1A was assessed by methylation-specific PCR. RASSF1A immunostaining was variable during the menstrual cycle in normal endometrium. RASSF1A expression was significantly reduced in 48% of endometrial carcinomas, particularly in tumors exhibiting microsatellite instability. RASSF1A-promoter methylation was very frequent in endometrial carcinoma (74%), and was frequently associated with reduced expression of RASSF1A. RASSF1A-promoter hypermethylation was common in advanced-stage endometrial carcinoma. The results suggest that reduced expression of RASSF1A may play a role in endometrial carcinogenesis by controlling cell proliferation and apoptosis through the MAPK-signaling pathway.

Nuclear factor-kappaB activation is associated with somatic and germ line RET mutations in medullary thyroid carcinoma.

The nuclear factor-kappaB (NF-kappaB) family of transcription factors regulates a wide variety of cellular processes including cell growth, differentiation, and apoptosis. NF-kappaB has been shown to be activated through several signaling pathways that involve growth factor receptors. The aim of the study was to assess the immunohistochemical expression of members of the NF-kappaB family and the putative targets of NF-kappaB in a series of medullary thyroid carcinomas (MTCs), in correlation with RET mutational status. A tissue microarray was constructed from paraffin-embedded blocks of 48 MTCs (13 familial, 35 sporadic) previously evaluated for germ line and somatic RET mutations. Immunohistochemical evaluation included members of the NF-kappaB (p50, p65, p52, c-Rel, RelB) family, as well as putative targets of NF-kappaB such as Flip, Bcl-xL, and cyclin D1. Nuclear immunostaining for members of NF-kappaB was frequent in MTCs (p50, 19%; p65, 68%; p52, 86.6%; c-Rel, 75%; RelB, 36%). MTCs with germ line or somatic RET mutations (29 cases) showed NF-kappaB nuclear translocation (particularly of p65, P = .035) more frequently than MTCs without RET mutations (19 cases). Immunostaining for putative targets of NF-kappaB showed a significant statistical association between p65 and Bcl-xL (P = .024). In addition, Bcl-xL expression was statistically higher in the tumors with exon 16 RET mutation in comparison with those with exon 10 and 11 RET mutations or wild-type RET (P = .002). Moreover, the significance of RETsignaling in NF-kappaB activation was evaluated in the RET-mutated TT cell line. TT cells were infected with lentiviruses carrying short hairpin RNA to knock down RET expression, and NF-kappaB activity was assessed by luciferase reporter assays. Silencing of RET in the TT cell line produced a significant decrease in NF-kappaB activation and reduction in ERK1/2. The results suggest that the NF-kappaB is frequently activated in MTCs. The results also support the hypothesis that RET activation by somatic or germ line mutations may be responsible for NF-kappaB activation in MTCs.

Metástasis cutáneas en carcinoma de hipofaringe / Cutaneous metastasis in hypopharyngeal carcinoma

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El síndrome del primer mordisco / First-bite syndrome

El síndrome del primer mordisco consiste en la aparición de dolor en la parótida al inicio de la masticación, por lesión de la cadena simpática cervical o del plexo simpático que inerva la parótida. El diagnóstico es fundamentalmente clínico en un paciente con antecedentes de cirugía del espacio parafaríngeo. Presentamos un paciente con síndrome del primer mordisco tras ser intervenido de schwannoma del simpático cervical(AU)

First-bite syndrome consists of the appearance of pain in the parotid at the beginning of mastication, due to damage to the cervical sympathetic chain or the sympathetic plexus innervating the parotid gland. Clinical presentation in a patient who has undergone surgery of the parapharyngeal space suggests the diagnosis. We report here the case of a patient who presented first-bite syndrome after being operated on for a cervical sympathetic chain schwannoma(AU)

Significación clínica de la asimetría amigdalina / Clinical significance of unilateral tonsillar enlargement

Introducción: El aumento unilateral asintomático de una amígdala palatina suele tratarse con amigdalectomía sistemática por sospecha de malignidad. Ante la mayor frecuencia de procesos benignos, se estudian datos clínicos que puedan servir como factores de riesgo para evitar amigdalectomías innecesarias. Material y métodos: Se revisan 267 amigdalectomías realizadas entre 1996 y 2006, de las cuales 30 se indicaron por asimetría. Se valoran factores de riesgo, como adenopatías, ser varón, mayor de 45 años, detección por el mismo paciente, aspecto sospechoso, clínica sistémica, historia de malignidad e inmunodeficiencia. Resultados: El resultado anatomopatológico fue de proceso benigno en el 80 % de los casos y maligno, en el 20 %. Los factores de riesgo que muestran mayor relación con malignidad son las adenopatías y el aspecto sospechoso.C onclusiones: Se puede realizar control estricto ante una asimetría amigdalina, aunque cuando hay factores de riesgo debemos indicar amigdalectomía (AU)

Introduction: Asymptomatic unilateral tonsillar enlargement is usually treated with systematic tonsillectomy under suspicion of malignancy. Due to the fact that most of the cases are benign pathologies, we set out to study the clinical signs that would help us in the diagnosis in order to avoid unnecessary tonsillectomies. Material and methods: We reviewed 267 tonsillectomies performed from 1996 to 2006 and 30 of these were indicated because of asymmetry. We evaluated risk factors for malignancy: cervical lymphatic node enlargement, sex, age, tonsillar enlargement noticed by the patient, suspicious appearance, systemic symptoms, history of malignancy and immune compromise. Results: Histopathologic study revealed 80 % to be benign and 20 % malignant. The risk factors with the strongest association were enlargement of cervical lymphatic nodes and suspicious appearance of the tonsil. Conclusions: Strict control of a unilateral tonsillar enlargement is possible, but it is mandatory to perform a tonsillectomy when the appearance of the tonsil raises suspicions or there are enlarged lymphatic nodes (AU)

Diagnóstico por imagen de hibernoma cervical / Image-based diagnosis of cervical hibernoma

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Fístula faringocutánea tras laringectomía total. Estudio de casos y controles de los factores de riesgo implicados en su aparición / Pharyngocutaneous fistula following total laryngectomy. A case-control study of risk factors implicated in its onset

Introducción y objetivos: La fístula faringocutánea es la complicación postoperatoria más frecuente de la laringectomía total. Los factores implicados en su aparición han sido estudiados por numerosos autores sin obtener resultados concluyentes. El principal objetivo de este estudio es conocer los factores de riesgo implicados en la aparición de fístulas en nuestro medio. Métodos: Diseñamos un estudio retrospectivo de casos y controles. Incluimos en ambos grupos a 33 pacientes a los que se practicó laringectomía total con el mismo protocolo en todos los casos. Excluimos a los pacientes en que se realizó una reconstrucción compleja para evitar sesgos. Resultados: Observamos que la extensión de la cirugía a la faringe es el único factor asociado significativamente (p = 0,04) a la aparición de fístulas en nuestro medio (odds ratio [OR] = 2,83). La asociación de radioterapia previa y vaciamientos cervicales muestra una tendencia importante (OR = 3,2), no significativa (p = 0,099). Otros factores como la edad del paciente, la radioterapia previa, los vaciamientos cervicales, la traqueotomía previa o la hemoglobina postoperatoria no se asocian estadísticamente a la aparición de esta complicación. La mayoría de las fístulas se cierran con medidas conservadoras (72,7 %), pero en pacientes irradiados previamente requieren reparación quirúrgica con mayor frecuencia que en los no irradiados (p < 0,01). Conclusiones: En nuestro medio el factor más asociado a la aparición de fístulas tras laringectomía es la extensión de la cirugía a la faringe. Las fístulas en pacientes irradiados tienen menor tendencia a la reparación conservadora y requieren cirugías más agresivas para solucionarlas (AU)

Introduction and objectives: Pharyngocutaneous fistula is the most frequent complication after total laryngectomy. Risk factors involved in its appearance have been studied by many authors without conclusive results. Our main objective is to identify the risk factors involved in the onset of fistulae at our institution. Methods: A retrospective case-control study was designed. Thirty-three patients subjected to total laryngectomy with the same protocol were included in both groups. Patients who required a complex surgical reconstruction were excluded in order to avoid biases. Results: The only risk factor with statistical significance (P=0.04) for the onset of fistulae in our setting is the extension of the surgery to the pharynx (OR=2.83). The association of prior radiotherapy and concurrent neck dissection displayed a notable trend (OR=0.32) but without significance (P=0.099). Patient age, prior radiotherapy, concurrent neck dissection, prior tracheotomy and post-operative haemoglobin level did not predispose to this complication in our study. Non-surgical closure of the pharyngocutaneous fistula was achieved in most cases (72.7 %) but patients who had pre-operative radiotherapy required surgical closure more frequently (P<0.01) than those not irradiated. Conclusions: At our centre the main risk factor associated with post-laryngectomy fistulae is the extension of surgery to the pharynx. In previously-irradiated patients, fistulae have a lower incidence of non-surgical closure and require more aggressive surgery to resolve them (AU)

Síndrome del seno silente / The silent sinus syndrome

El síndrome del seno silente es una afección muy poco frecuente. Se describe como un enoftalmos unilateral secundario a colapso y opacificación del seno maxilar sin síntomas nasosinusales. La obstrucción del complejo osteomeatal es el factor fisiopatológico desencadenante. El diagnóstico se basa en los hallazgos clínicos y radiológicos. El tratamiento irá dirigido a restablecer la ventilación del seno y, si es necesario, corregir el suelo orbitario. Presentamos el caso de una mujer diagnosticada y tratada en nuestro hospital por esta entidad

The silent sinus syndrome is a very infrequent pathology. It is described as an enophthalmos secondary to collapse and opacification of maxillary sinus without presenting sinus or nasal symptoms. Osteomeatal complex obstruction is the triggering physiopathologic factor. The clinical symptoms and imaging findings lead to the diagnosis. The treatment consists in restoring sinus ventilation and, if necessary, correcting the orbital floor. We report a case of a woman who was diagnosed and treated because of this entity in our hospital

Estado actual del tratamiento de la otoesclerosis / No disponible

Los autores realizan una revisión bibliográfica de la literaturareciente sobre el tratamiento de la otoesclerosis.Se comprueba que la idea inicial de Shea al realizar laprimera platinectomía hasta hoy no ha variadosustancialmente. Se analizan algunos aspectos frecuentementesometidos a debate, como el tratamiento médico,la edad ideal para realizar la intervención quirúrgica,la posibilidad de cirugía ambulatoria. En el aspecto técnicose analiza la literatura actual de la estapedectomíatotal, parcial y la estapedotomía, los medios para realizarla platinotomía, los diferentes tipos de prótesis y eldenominado sellado de la ventana oval. Por último seestudian algunas técnicas menos habituales como la conservacióndel tendón del estribo o la estapedotomía desdeel mango del martillo

The authors do a bibliographic review on the recent articlesabout otosclerosis treatment. It is verified that Shea's initialidea of the first platinectomy hasn't been changedsignificantly to date. They analize some different aspectsoften discussed: the medical treatment, the best age toperform the surgery, the outpatient-surgery management.They review some articles about technical aspects focusingon total and partial stapedectomy, stapedotomy, thedifferent means to do the platinectomy, the several typesof prosthesis used, and the so-called oval window seal.Finally they analize several infrequent techniques asstapedius tendon preservation and malleostapedotomy

Extirpación de pólipos antrocoanales mediante cirugía endoscópica / No disponible

Los pólipos antrocoanales son estructuras polipoides originadas en el seno maxilar que se extienden a la fosa nasal. Su aparición es independiente de fenómenos alérgicos. En nuestra serie representan un 7,1% del total de intervenciones por poliposis nasosinusal. Deben sospecharse ante la presencia de una obstrucción nasal, sobre todo en niños. Para su estudio es necesario realizar una exploración ORL, endoscopia nasal y TC. La técnica quirúrgica de elección es la cirugía endoscópicana sosinusal, pero puede ser interesante asociar una antrostomía en la fosa canina si no se puede extirpar toda la mucosa patológica. Bajo este supuesto el porcentaje de recidivas que hemos observado es del 11,1%. La estancia media de nuestros pacientes tras la intervención fue de 1,3 días, sin aparecer complicaciones remarcables, por lo que creemos que la intervención puede ser realizada mediante cirugía ambulatoria

Antrochoanal polyps are polypoid structures that arise from the maxillary sinus and extend into the nose. Its appearance is independent from allergic processes. In our sample they represent 7.1% of the sinusal polyposis operations. We must suspect them in patients with nasal obstruction, especially in children. The study of these polyps includes a complete ENT examination, nasal endoscopy and CT-scan. Nowadays endoscopicsinus surgery is the surgical choice, but it would be interesting to add a little antrostomy in the canine fosa if we were not able to complete the surgical removal of all diseased mucosa. Under this assumption ourrelapse rate has been 11.1%. The mean stay of our patients before surgery has been 1.3 days, without any important postoperative complication, so we think that these patients could be operated in an out-patient surgical department