Tinnitus pulsátil: caso clínico y revisión de la literatura / Pulsatile tinnitus: clinical case and review

RESUMEN El tinnitus pulsátil es un síntoma otológico infrecuente pero requiere un estudio acabado. Una historia y examen físico detallados, son primordiales para orientar el estudio imagenológico posterior, con lo que se llega al diagnóstico en gran parte de los casos. El tratamiento debe ser dirigido a corregir la causa subyacente. En este trabajo, se presenta un caso clínico de tinnitus pulsátil, revisión del tema y orientación al enfoque diagnóstico.

ABSTRACT Pulsatile tinnitus is an infrequent otologic symptom but requires a thorough study. A detailed history and physical examination are essential to guide the subsequent imaging study, with which the diagnosis is reached in a large number of cases. The treatment should be aimed at correcting the underlying cause. In this study, a clinical case of pulsatile tinnitus, review of the subject and orientation to the diagnostic approach is presented.

Rinosporidiosis nasal: reporte de un nuevo caso y revisión de la literatura / Nasal rhinosporidiosis: new case report and review

La rinosporidiosis es una enfermedad granulomatosa rara producida por el microorganismo Rhinosporidium seeberi. A pesar de ser considerada una infección endémica en algunas zonas de Asia, en nuestro país es una enfermedad extremadamente rara. Se presenta el caso clínico de un escolar de 10 años que consulta por aumento de volumen en fosa nasal izquierda de 1 mes de evolución, de crecimiento progresivo, con epistaxis autolimitada, presentando al examen físico una lesión polipoídea, en la cual, no existiendo sospecha previa, se determinó mediante histopatología la presencia de rinosporidio-sis. Se discute la epidemiología de la enfermedad, sus mecanismos de diseminación, alternativas de tratamiento y principales complicaciones.

Rhinosporidiosis is a rare granulomatous disease produced by the microorganism Rhinosporidium seeberi. Despite being considered an endemic infection in some areas of Asia, in our country it is an extremely rare disease. We present the case of a 10 year-old boy who consult for increased volumen in the left nostril of 1 month evolution, with progressive growth, self-limited epistaxis, and a physical examination with a polypoid lesion, in which there were no prior suspicion, histopathology determined the presence of rhinosporidiosis. Epidemiology of the disease, its dissemination mechanisms, treatment options and major complications are discussed.

Quiste de primer arco branquial, reporte de caso y revisión de la literatura / First branchial arch cyst, case report and review of the literature

Los quistes branquiales de primer arco son una malformación congénita de baja frecuencia. Se desarrollan por la fusión incompleta de la hendidura faríngea entre el primer y el segundo arco branquial. Pueden permanecer silentes por mucho tiempo y manifestarse cuando se sobreinfectan, causando significativa morbilidad. Por lo general, se presentan en la infancia, pero muchas veces su diagnóstico es tardío ya que son difíciles de diferenciar de adenopatías u otras masas, debiendo ser considerados dentro del diagnóstico diferencial de masa cervical y parotídea, especialmente en pacientes jóvenes. La cirugía es el tratamiento definitivo, requiriendo una escisión completa del quiste y su trayecto fistuloso para evitar las recurrencias. Debido a su localización intra-parotídea y complejidad morfológica, es necesario conocer la anatomía en detalle para evitar lesionar el nervio facial. En esta revisión, se pretende presentar las características clínicas y resultados quirúrgicos en una paciente lactante con diagnóstico de quiste de primer arco, asícomo efectuar una revisión de la literatura.

First branchial arch cysts are very infrequent congenital malformations. Their development is due to an incomplete fusion of the pharyngeal cleft between the first and second branchial arch. They can remain silent for a very long time and manifest when they become infected, causing significant morbidity. In general, they present in child-hood, but many times its diagnosis occurs on a late onset since they are difficult to differentiate from lymphadenopathies or other masses. So, they should be considered on the differential diagnosis of cervical and parotid masses, especially in young patients. Surgery is its definitive treatment. Complete excision of the cyst and its fistula must be performed to avoid recurrences. Due to its intraparotid localization and morphological complexity it is necessary to understand the anatomy in detail to avoid facial nerve le-sions. In this revision, we aim to present clinical characteristics and surgical outcomes in an infant with the diagnosis of first branchial arch cyst and to review the literature.

Dacriocistorrinostomía endoscópica: experiencia de 4 años del Hospital Clínico de la Universidad de Chile / Endoscopic dacryocystorhinostomy: four years experience at the Clinical Hospital of the University of Chile

Introducción: La dacriocistorrinostomía abierta es el gold estándar para el tratamiento de la obstrucción nasolacrimal, patología manifestada como epífora crónica, dacriocistitis y conjuntivitis recurrente. Desde el desarrollo del abordaje endonasal, se ha considerado como una alternativa terapéutica eficaz con notorias ventajas respecto a la técnica abierta y que además ofrece la posibilidad de corregir otras alteraciones de la nariz y cavidades paranasales en el mismo tiempo quirúrgico. Objetivo: Evaluar los resultados de la técnica quirúrgica endoscópica según la realidad del Hospital Clínico de la Universidad de Chile, durante los años 2010-2014. Determinar la etiología de la obstrucción en los pacientes intervenidos. Material y método: Se realizó un estudio de cohorte retrospectivo con revisión de fichas clínicas de pacientes con diagnóstico de obstrucción de la vía lacrimal sacular y postsacular sometidos a dacriocistorrinostomía endoscópica. Se incluyeron 27pacientes entre los cuales se realizaron 33 cirugías, ya que 22,2% de ellos (6/27) fueron sometidos a intervención bilateral. Resultados: El éxito quirúrgico objetivo y subjetivo se presentó en 75,8% (25/33) y 65,4% (17/26) respectivamente. El 7,4% (2/27) presentaron complicaciones intraoperatorias (falsa vía y extrusión de grasa orbitaria) y 18,5% (5/27) complicaciones posoperatorias (sinequias y fibrosis). Dentro de las causas destacan: idiopática 66,7% (18/27), postraumática 14,8% (4/27), secundaria a utilización de radioyodo 11,1% (3/27), granulomatosis de Wegener3,7% (1/27)y congénita 3,7% (1/27). La sonda instalada se mantuvo por un promedio de 3,5 meses, y el seguimiento se realizó por un periodo de 7,4 meses. Conclusión: La dacriocistorrinostomía endoscópica resulta ser una excelente herramienta quirúrgica para el manejo de pacientes con diagnóstico de obstrucción nasolacrimal, siendo un procedimiento exitoso, seguro, con baja tasa de complicaciones y una muy buena evolución posoperatoria, recomendado para todos aquellos casos con mala respuesta a las terapias médicas.

Introduction: Open dacryocystorhinostomy is the gold standard for the treatment of nasolacrimal obstruction, pathology manifested as chronic epiphora, recurrent dacryocystitis and conjunctivitis. Since the development of endonasal approach, it has been considered as an alternative therapy with notable advantages over the open technique and offers the possibility to correct other abnormalities of the nose and paranasal sinuses in the same surgical time. Aim: To evaluate the results of endoscopic surgical technique according to the reality of the Clinical Hospital of the University of Chile, during the years 2010-2014. Determine the etiology of the obstruction in patients undergoing surgery. Material and method: A retrospective cohort study was performed with review of clinic files of patients diagnosed with lacrimal duct obstruction submitted to an endoscopic dacryocystorhinostomy. 27 patients were included and 33 surgeries were performed, as 22.2% of them (6/27) underwent bilateral intervention. Results: Objective and subjective surgical success occurred in 75,8% (25/33) and 65,4% (17/26) respectively. 7,4% (2/27) had intraoperative complications (false passage and orbital fat extrusion) and 18,5% (5/27) postoperative complications (fibrosis and synechiae). Among the causes are: idiopathic 66,7% (18/27), postraumatic 14.8% (4/27), history of radioiodine use 11.1% (3/27), Wegener's granulomatosis 3.7% (1/27) and congenital 3.7% (1/27). Probe Installed was kept for an average of 3,5 months, and the follow-up was performed for 7,4 months. Conclusions: Endoscopic dacryocystorhinostomy is an excellent surgical tool for the management of patients with nasolacrimal obstruction. It's a successful procedure, with low rate of complications and good postoperative outcome, recommended for those cases with poor response to medical therapies.

Schwannoma del nervio facial y sus ramas en el oído medio: reporte de 3 casos y revisión de literatura / Schwannoma of the facial nerve and its branches in the middle ear: a report of 3 cases and literature review

El schwannoma del nervio facial (SNF) es un tumor infrecuente, sin embargo es el tumor más frecuente del nervio facial. Son tumores benignos de crecimiento lento que producen sintomatología otológica no específica y pueden asociar parálisis facial. No existen exámenes preoperatorios que nos permitan diagnosticar con certeza el SNF. El estudio de elección se realiza con TC de alta resolución y RM con gadolinio. El diagnóstico definitivo es histopatológico pero se puede hacer diagnóstico presuntivo si la clínica, imágenes y hallazgo intraoperatorios son concordantes. El objetivo del tratamiento debe intentar preservar la función del nervio facial por el mayor tiempo posible. En casos de pacientes asintomáticos, o sin compromiso del nervio facial, se prefiere la observación. Se presentan en este artículo casos de schwannomas del facial intratimpánico y de cuerda del tímpano.

The facial nerve schwannoma (SNF) is a rare tumor, however it is the most common tumor of the facial nerve. They are slow-growing benign tumors that produce non-specific otologic symptoms and may be associated facial paralysis. There are no preoperative tests that allow us to accurately diagnose the SNF. The study of choice is made with high resolution CT and MRI with gadolinium. Definitive diagnosis is histopathological but the physician may make a presumptive diagnosis if clinical images and intraoperative findings are consistent. The goal of treatment should try to preserve facial nerve function for as long as possible. In cases of asymptomatic patients, without facial nerve involvement, observation is prefered. Cases of schwannomas of intratympanic facial and chorda tympani are presented in this article.

Adenoma carcinoide de oído medio / Middle ear carcinoid adenoma

Las neoplasias primarias de oído medio son poco frecuentes y más aún lo es el adenoma de oído medio. Se plantea que el tumor se origina de células pluripotenciales endodérmicas indiferenciadas que están presentes en la mucosa. El adenoma carcinoide está compuesto por dos tipos de células: exocrinas y neuroendocrinas, estas últimas son capaces de liberar granulaciones y neuropéptidos que se detectan en la inmunohistoquímica. La mayoría se presentan con síntomas vagos de la esfera otológica, siendo raras las manifestaciones sistémicas de síndrome carcinoide. No existe examen físico característico ni patrón imagenológico. Se debe hacer diagnóstico diferencial con colesteatoma y otros tumores de oído medio. El diagnóstico definitivo es anatomopatológico y el tratamiento de elección es quirúrgico dado el potencial destructivo local. Se presentan en este artículo dos casos de adenoma carcinoide de oído medio.

Primary neoplasms of the middle ear are rare and even more so is the middle ear adenoma. It is stated that the tumor originates from undifferentiated endodermal stem cells that are present in the mucosa. Carcinoid adenoma is compromised of two cell types; exocrine and neuroendocrine cells, the latter are able to release neuropeptides and granulations that can be detected in immunohistochemistry. Most cases present with vague symptoms of the otologic sphere, being less common the systemic manifestations of carcinoid syndrome. There is no physical examination or characteristic imaging pattern. Differential diagnosis must be done with cholesteatoma and other middle ear tumors. The definitive diagnosis is anatomopathological and the treatment of choice is surgery given the local destructive potencial. Two cases of middle ear carcinoid adenoma are presented in this article.

Vértigo postural paroxístico benigno subjetivo / Subjective benign paroxysmal positional vertigo

El vértigo postural paroxístico benigno (VPPB) es el trastorno vestibular más frecuente y se asocia a alto grado de morbilidad, impacto psicosocial y gastos médicos. El diagnóstico se basa en la anamnesis y examen físico incluyendo maniobras específicas para desencadenarlo. En algunos casos, podemos observar pacientes que presentan clínica de VPPB pero al realizar la maniobra de Dix-Hallpike no presentan nistagmo observable a simple vista, ni medible con lentes de frenzel ni videonistagmografía, pese a que manifiestan vértigo con o sin síntomas neurovegetativos. A estos casos Haynes los denominó "VPPB subjetivo" y representan entre el 11,5% y 48% del total de los VPPB. Estos pacientes también se beneficiarían de maniobras de reposición, con similares tasas de recurrencia que aquellos VPPB considerados objetivos dada la presencia de nistagmo con las maniobras de provocación.

Benign paroxysmal positional vertigo (BPPV) is the most common vestibular disorder and is associated with high morbidity, psychosocial impact and medical expenses. Diagnosis is based on history and physical examination including specific maneuvers to trigger it. In some cases, patients with BPPV do not present observable nystagmus to the naked eye, or measureable with frenzel lenses or videonystagmography with the Dix-Hallpike test, although they manifested vertigo with or without autonomic symptoms. Haynes et al called this entity "subjective BPPV". They represent between 11.5 and 48% of all BPPV. These patients can benefit from repositioning maneuvers, with similar rates of recurrence than those considered objective BPPV.

Microencapsulated cell-mediated treatment of inoperable pancreatic carcinoma.

Pancreatic cancer can seldom be resected, and chemotherapy has only a limited effect on survival or tumour load. We did a phase I/II trial in 14 patients with pancreatic cancer to assess the safety of local activation of low-dose ifosfamide. We encapsulated genetically modified allogeneic cells, which expressed a cytochrome P450 enzyme, in cellulose sulphate and delivered them by supraselective angiography to the tumour vasculature. These cells locally activated systemically administered ifosfamide. The tumours of four patients regressed after treatment, and those of the other ten individuals who completed the study remained stable. Median survival was doubled in the treatment group by comparison with historic controls, and 1-year survival rate was three times better. Further studies of this cell-therapy-based treatment combined with chemotherapy for inoperable pancreatic cancer are warranted.

Necrotic, rather than apoptotic, cell death caused by cytochrome P450-activated ifosfamide.

Feline kidney cells were transfected with a vector overexpressing cytochrome P450 2B1 (CYP2B1). Transfected cells acquired a new specific biochemical activity, which could be demonstrated by a rapid CYP2B1 detection assay and showed selective sensitivity to the antitumorigenic prodrug ifosfamide (IFO). Further, the cell-killing effect was also mediated on nonmodified cells like feline kidney cells, mouse lymphoma, and human pancreatic cells in the vicinity of the CYP2B1-expressing cells due to the diffusible nature of the activated IFO metabolites. One of these, phosphoramide mustard, causes interstrand DNA cross-linking and it has been thought that the inability to repair this damage results in apoptosis. Surprisingly, our results clearly demonstrate a necrotic mechanism of IFO-induced cell death. This may have important implications for the activation of the immune system during CYP2B1/IFO suicide gene therapy of cancer.

Combined chemotherapy of murine mammary tumors by local activation of the prodrugs ifosfamide and 5-fluorocytosine.

The success of chemotherapeutic intervention is limited because the necessary high local drug doses cannot be achieved without systemic toxicity. Application of suicide genes (SGs) and direct conversion of prodrugs (PDs) to toxic metabolites in situ by SGs may enhance the efficacy of chemotherapy. To evaluate this strategy in two murine breast cancer models, TS/A and GR, we injected cellulose sulfate capsules harboring cat kidney cells expressing the SGs cytosine deaminase and cytochrome P450 2B1 (CYP2B1) intratumorally. The PDs 5-fluorocytosine and ifosfamide were administered in 3-day intervals. The effect of in situ chemotherapy with each PD alone and the combination was analyzed over a period of 100 days. The results reveal that for TS/A tumors, the antitumoral effect mediated by CYP2B1 is more efficient than that of cytosine deaminase, whereas for GR tumors, both systems worked equally well. Furthermore, we find additive toxicity using both SG/PD systems for both TS/A and GR tumors.

Development of cellulose sulfate-based polyelectrolyte complex microcapsules for medical applications.

Microencapsulation, as a tool for immunoisolation for allogenic or xenogenic implants, is a rapidly growing field. However most of the approaches are based on alginate/polylysine capsules, despite this system's obvious disadvantages such as its pyrogenicity. Here we report a different encapsulation system based on sodium cellulose sulfate and polydiallyldimethyl ammonium chloride for the encapsulation of mammalian cells. We have characterized this system regarding capsule formation, strength and size of the capsules as well as viability of the cells after encapsulation. In addition, we demonstrate the efficacy of these capsules as a "microfactory" in vitro and in vivo. Using encapsulated hybridoma cells we were able to demonstrate long-term release of antibodies up to four months in vivo. In another application we could show the therapeutic relevance of encapsulated genetically modified cells as an in vivo activation center for cytostatic drugs during tumor therapy.

Characterization of a human cell clone expressing cytochrome P450 for safe use in human somatic cell therapy.

We have previously demonstrated the therapeutic effect and efficacy of implantation of cells genetically modified to express cytochrome P450 2B1 in a nude mouse tumor model. The cells are encapsulated in polymerized cellulose sulphate and injected into preformed tumors. Upon administration of ifosfamide, the P450 enzyme converts the ifosfamide into antitumorigenic toxic metabolites at the site required, thereby significantly reducing tumor burden. Feline kidney epithelial cells were chosen for these studies, because they are easy to culture and can readily be transfected. However, these cells are not suitable for eventual use in human patients, since they are known to express endogenous retroviruses that are able to infect mammalian cells. They thus represent a safety risk. Here we describe the establishment of a human cell line that has been genetically modified to express the same cytochrome P450 construct and their characterization. The usefulness of mitomycin C treatment, both to protect the cells from the toxic metabolites that they produce and to incapacitate these cells from replicating, should they escape from the capsules, has also been investigated.

Injection of encapsulated cells producing an ifosfamide-activating cytochrome P450 for targeted chemotherapy to pancreatic tumors.

The prognosis of pancreatic cancer is poor, and current medical treatment is mostly ineffective. The aim of this study was to design a new treatment modality in an animal model system. We describe here a novel treatment strategy employing a mouse model system for pancreatic carcinoma. Embryonal kidney epithelial cells were genetically modified to express the cytochrome P450 subenzyme 2B1 under the control of a cytomegalovirus (CMV) immediate early promoter. This CYP2B1 gene converts ifosfamide to its active cytotoxic compounds, phosphoramide mustard, which alkylates DNA, and acrolein, which alkylates proteins. The cells were then encapsulated in a cellulose sulphate formulation and implanted into preestablished tumors derived from a human pancreatic tumor cell line. Intraperitoneal administration of low-dose ifosfamide to tumor bearing mice that received the encapsulated cells results in partial or even complete tumor ablation. Such an in situ chemotherapy strategy utilizing genetically modified cells in an immunoprotected environment may prove useful for solid tumor therapy in man.

Targeted chemotherapy by intratumour injection of encapsulated cells engineered to produce CYP2B1, an ifosfamide activating cytochrome P450.

The prognosis of pancreatic adenocarcinoma is poor and current treatment ineffective. A novel treatment strategy is described here using a mouse model system for pancreatic cancer. Cells that have been genetically modified to express the cytochrome P450 2B1 enzyme are encapsulated in cellulose sulphate and implanted into pre-established tumours derived from human pancreatic cells. Cytochrome P450 2B1 converts the chemotherapeutic agent ifosfamide to toxic metabolites. Administration of ifosfamide to tumour-bearing mice that were recipients of implanted encapsulated cells results in partial or even complete tumour ablation. These results suggest that in situ chemotherapy with genetically modified cells in an immunoprotected environment may prove useful for application in man.

Intratumoral injection of encapsulated cells producing an oxazaphosphorine activating cytochrome P450 for targeted chemotherapy.

The prognosis of pancreatic adenocarcinoma is poor and current treatment is for the most part ineffective. We describe here a novel treatment strategy using a mouse model system for pancreatic cancer. Human embryonic epithelial cells have been genetically modified to express the cytochrome P450 2B1 enzyme under the control of a CMV immediate-early promoter. This CYP2B1 gene converts oxazaphosphorines (ifosfamide or cyclophosphamide) to their active cytotoxic compounds, phosphoramide mustard, which alkylates DNA, and acrolein, which alkylates proteins. A number of assays were performed to demonstrate the CYP2B1 gene function as well as toxic effects on neighbouring cells (bystander effect). The cells were then encapsulated in a cellulose sulphate formulation shown to be well tolerated in the pancreas of immunocompetent mice, and injected 1 cm away from pre-established tumours derived from a human pancreatic tumour cell line (PaCa-44). Intraperitoneal administration of low-dose ifosfamide to tumour bearing mice that received the encapsulated cells results in partial or even complete tumour ablation. Such an in situ chemotherapy strategy utilizing genetically modified cells in an immunoprotected environment may prove useful for solid tumour therapy in man.