Cáncer de endometrio: tratamiento quirúrgico en un hospital comunitario de España / Endometrial cancer: surgical treatment in a community hospital in Spain

Resumen OBJETIVO: Exponer los desenlaces quirúrgicos de las pacientes intervenidas por cáncer de endometrio, analizar si existen puntos de mejora en nuestra práctica clínica y aportar más datos a la evidencia publicada, para ayudar al avance en el tratamiento quirúrgico de las pacientes con esta enfermedad MATERIALES Y MÉTODOS: Estudio observacional, descriptivo y retrospectivo llevado a cabo en la Unidad de Oncología Ginecológica del Hospital Regional Virgen Macarena de Sevilla, España, entre junio de 2013 y febrero de 2020. Se reunieron los reportes quirúrgicos de pacientes intervenidas por alguna afección endometrial premaligna o maligna. Variables de estudio: edad, IMC, cirugías previas, diagnóstico histopatológico y estadio, vía de acceso quirúrgico y terapia coadyuvante. Se exponen los desenlaces relacionados con complicaciones quirúrgicas y tasa de curación, así como el tiempo de intervención, vía de acceso quirúrgico y estancia hospitalaria. RESULTADOS: Se estudiaron 250 pacientes, la mayoría (76%) con diagnóstico de adenocarcinoma endometrioide de endometrio. La vía de acceso quirúrgico más utilizada fue la laparoscopia (51.6%), con un porcentaje de complicaciones intraoperatorias del 10% y posoperatorias del 9.2%. El 88.4% de las pacientes permanece viva y libre de enfermedad después del tratamiento, con recaídas solo en el 11.6% y 8% de fallecimientos. CONCLUSIONES: El tratamiento inicial de elección, en pacientes con hiperplasia con atipias o cáncer de endometrio en estadios tempranos, es la cirugía, mediante histerectomía, doble anexectomía y en algunos casos linfadenectomía asociada. La elección de la vía quirúrgica de acceso debe individualizarse a las condiciones particulares de cada paciente. La laparoscopia ofrece múltiples ventajas, es una técnica en auge y cada día más practicada.

Abstract OBJECTIVE: To expose the surgical outcomes of patients operated on for endometrial cancer, to analyze if there are points of improvement in our clinical practice and to contribute more data to the published evidence, to help advance the surgical treatment of patients with this disease. MATERIALS AND METHODS: Observational, descriptive, and retrospective study carried out in the Gynecologic Oncology Unit of the Virgen Macarena Regional Hospital of Seville, Spain, between June 2013 and February 2020. Surgical reports of patients operated on for any premalignant or malignant endometrial condition were collected. Study variables: age, BMI, previous surgeries, histopathological diagnosis and stage, surgical access route and adjuvant therapy. Outcomes related to surgical complications and cure rate are presented, as well as operation time, surgical access route and hospital stay. RESULTS: 250 patients were studied, the majority (76%) with a diagnosis of endometrioid endometrial adenocarcinoma. The most used surgical access route was laparoscopy (51.6%), with a percentage of intraoperative complications of 10% and postoperative complications of 9.2%. 88.4% of patients remain alive free of disease after treatment, with relapses in only 11.6% and 8% deaths. CONCLUSIONS: The initial treatment of choice in patients with hyperplasia with atypia or early-stage endometrial cancer is surgery, by hysterectomy, double adnexectomy and in some cases associated lymphadenectomy. The choice of surgical approach must be individualized to the conditions of each patient. Laparoscopy offers multiple advantages; it is a technique that is on the rise and is being used more and more frequently.

Carcinoma papilar difuso de tiroides: microcalcificaciones fuera del nódulo tiroideo / Diffuse Papillary Thyroid Carcinoma: Microcalcifications Outside the Thyroid Node

Resumen: Introducción: La incidencia de cáncer papilar de tiroides (PTC) ha aumentado de 1975 a 2015. Basados en criterios publicados, el ultrasonido (US) es muy efectivo para predecir el riesgo de malignidad. Todos estos criterios se enfocan en los nódulos tiroideos; sin embargo, 2% de los casos se pueden presentar como focos ecogénicos difusos sin un nódulo identificable. Caso: Mujer de 17 años con historia de 3 meses con una masa palpable en la región anterior derecha del cuello, sin otros síntomas. El US de cuello revela múltiples focos ecogénicos de distribución difusa en el parénquima tiroideo con un nódulo de 6 mm TI-RADS 5 en el lóbulo izquierdo y ganglio linfáticos con componentes sólidos y quísticos, pérdida del hilio graso y con puntos ecogénicos. Se le realizó tiroidectomía total con linfadenectomía bilateral. Discusión: Las microcalcificaciones son muy sugestivas de CPT. Los ecos puntiformes se correlacionan en patología con una forma de calcificación distrófica llamada cuerpos de Psammoma, los cuales se depositan en tejido no viable. La tiroiditis crónica también puede presentar calcificaciones distróficas. Por lo tanto, un parénquima tiroideo normal con presencia de microcalcificaciones, obliga a realizar una biopsia con aguja fina para descartar CPT. Estudios recientes sugieren que la lobectomía es una opción viable y debe ser la primera elección en CPT localizado (< 2 cm). Sin embargo, esto no se debe realizar en estos pacientes, ya que la presencia de microcalcificaciones difusas nos indica un tamaño del tumor mucho mayor y resultaría en un pronóstico desfavorable. Conclusión: Las microcalcificaciones difusas deben obligar al radiólogo a sospechar la variedad difusa del CPT como primera sospecha diagnóstica.

Abstract: Introduction: The incidence of thyroid papillary cancer (PTC) has increased from 1975 to 2015. Ultrasound is effective for predicting thyroid malignancy based on published criteria. All of these criteria focus on thyroid nodules but also 2% of the cases may appear as diffuse punctuate echogenic foci without an identifiable nodule. Case: A 17-year-old female with a 3-month history of a palpable mass on the right anterior side of the neck without any further symptoms. Neck ultrasound revealed multiple punctuate echogenic foci scattered along the thyroid parenchyma with a 6 mm nodule TI-RADS 5 on the left lobe, lymph nodes with cystic and solid components, loss of echogenic hilum and punctuate echogenic foci. The patient underwent a total thyroidectomy with bilateral lymphadenectomy. The pathology report revealed diffuse distribution of papillary cancer with a nodule on the left lobe and metastatic disease on the lymph nodes. Discussion: Microcalcifications are highly suggestive of PTC. Punctuate echogenic foci correlate in pathology with a form of dystrophic calcifications, called Psammoma bodies, which are deposited in nonviable tissue. Chronic thyroiditis may also present dystrophic calcifications. Thus, a normal thyroid parenchyma with microcalcifications should encourage the radiologist to perform a fine-needle aspiration biopsy (FNAB). Recent studies suggest that lobectomy is a viable option and should be pursued in the setting of localized PTC (<2 cm). A lobectomy should not be performed in patients with diffuse microcalcifications since it would result in an unfavorable outcome. Conclusions: Diffuse microcalcifications should immediately make the radiologist suspect diffuse PTC as a first diagnostic option.

High grade adenosarcoma of endocervix and endometrial cavity with a heterologous component of rhabdomyosarcoma. Case report and review of the literature / Adenosarcoma de alto grado de endocérvix y cavidad endometrial con componente heterólogo de rabdomiosarcoma. reporte de caso y revisión de la literatura

RESUMEN Objetivo: presentar el caso de una paciente con diagnóstico de adenosarcoma de alto grado de endocérvix y de cavidad endometrial, con componente heterólogo, y hacer una revisión de la literatura con especial atención al diagnóstico y manejo terapéutico de esa patología. Materiales y métodos: Se presenta el caso de una paciente de 31 años, que consulta al Hospital Universitario Virgen Macarena de Sevilla, institución regional de tercer nivel, por presentar san grado genital originado por una masa polipoidea endocervical que se llevó a biopsia con resultado de un leiomiosarcoma poco diferenciado de alto grado de endocérvix. Posteriormente fue llevada a histerectomía total abdominal. En el estudio de la pieza quirúrgica el resultado fue: adenosarcoma de endocérvix y cavidad endometrial, con componente heterólogo de rabdomiosarcoma. Con los términos: "adenosarcoma", "endocervical", "cérvix", "uterus", "heterologous", en las bases de datos Medline vía PubMed se realizó una búsqueda de artículos de revisión bibliográfica, reportes y series de casos clínicos que describían aspectos del adenosarcoma cervicouterino y del componente heterólogo de rabdomiosarcoma, en inglés y español, publicados desde 1974. Resultados: se hallaron seis artículos correspondientes a revisiones de la literatura, reportes o series de casos, donde se describen los aspectos más importantes referentes al diagnóstico y tratamiento de esta patología. Conclusiones: esta patología se caracteriza, en ocasiones, por un crecimiento rápido y agresivo, donde es importante el diagnóstico precoz y el tratamiento óptimo, basado en una combinación de cirugía, radioterapia y quimioterapia, aunque dada su baja prevalencia se necesitan aún más estudios para poder confirmar estos datos.

ABSTRACT Objective: To present the case of a patient diagnosed with high grade adenosarcoma of the endocervix and the endometrial cavity, with a heterologous component, and to conduct a review of the literature focusing on the diagnosis and therapeutic management of this disease condition. Materials and methods: We present the case of a 31-year-old female patient who came to Virgen Macarena University Hospital of Seville, a Level III regional institution, complaining of genital bleeding arising from an endocervical polypoid mass. The biopsy of the mass revealed a high grade, poorly differentiated leiomyosarcoma of the endocervix. The patient was taken later to total abdominal hysterectomy. The study of the surgical specimen provided the following result: adenosarcoma of the endocervix and endometrial cavity with a heterologous rhabdomyosarcoma component. A search was conducted in the Medline database via Pubmed using the terms "adenosarcoma," "endocervical," "cervix," "uterus," "heterologous." The search included literature review articles, case reports and clinical case series describing aspects of cervical adenosarcoma and the heterologous rhabdomyosarcoma component, published in English and Spanish since 1974. Results: Six articles corresponding to literature reviews, case reports or case series in which the most relevant aspects of the diagnosis and treatment of this disease condition are described were retrieved. Conclusions: This condition is characterized, on occasions, by rapid and aggressive growth, hence the importance of early diagnosis and optimal treatment based on a combination of surgery, radiation therapy and chemotherapy. However, due to its low prevalence, further studies are needed in order to confirm these data.

Carcinoma de ovario en paciente con mutación del gen BRCA1. Diagnóstico tras biopsia de adenopatía cervical, en el contexto de un síndrome paraneoplásico cutáneo / Ovarian carcinoma in a patient with a BRCA1 gene mutation. Diagnosis after biopsy of cervical adenopathy, in the context of a cutaneous paraneoplastic syndrome

RESUMEN El cáncer epitelial de ovario representa uno de los tumores ginecológicos más letales ya que más del 75% de las pacientes son diagnosticadas en estadío avanzado. Aún no se ha demostrado que la realización de pruebas y exámenes pélvicos rutinarios haya reducido la mortalidad, no existiendo actualmente, un cribado eficaz para su diagnóstico precoz. Aunque la sintomatología metastásica extraperitoneal más común es el derrame pleural, las linfadenopatías neoplásicas a nivel supraclavicular aparecen hasta en el 4% de casos, generalmente asociándose a un mal pronóstico. La identificación de una adenopatía supraclavicular se relaciona hasta en un 58-83% de los casos, con el hallazgo de una tumoración maligna. Por otro lado, la dermatomiositis del adulto puede tener un origen paraneoplásico en un 15-25% de las ocasiones, siendo el cáncer de mama y de ovario la etiología más frecuente en la población femenina. Las pacientes portadoras de mutaciones en los genes BRCA 1 y 2 tienen un aumento del riesgo de padecer neoplasias de mama y ovario. En aquellas afectas de un cáncer de ovario y portadoras de una mutación en los genes BRCA, no se debería plantear una cirugía profiláctica de rutina sobre la mama, al menos en los primeros 5 años tras el diagnóstico de la neoplasia ovárica. Presentamos el caso de una paciente portadora de una mutación germinal del gen BRCA 1, que debuta con un cáncer de ovario, tras el estudio de una adenopatía neoplásica de cuello, biopsiada en el contexto de un síndrome paraneoplásico cutáneo.

ABSTRACT Epithelial ovarian cancer represents one of the most lethal gynecological tumors, since more than 75% of affected women are diagnosed at an advanced stage. However, studies have not demonstrated yet that performing routine pelvic exams and tests had reduced mortality in ovarian cancer, and currently there is no effective screening for early diagnosis. The most common extraperitoneal metastatic symptomatology of ovarian cancer is pleural effusion, but there are other, like neoplastic lymphadenopathies at supraclavicular level, described in up to 4% of cases and generally related to a poor prognosis. The identification of a supraclavicular adenopathy is associated with the finding of a malignant tumor in 58-83% of the cases. On the other hand, adult dermatomyositis can have a paraneoplastic origin in 15-25% of patients, being breast and ovarian cancer the most frequent etiology in the female population. Patients with BRCA 1 and 2 genes mutations have an increased risk of breast and ovarian malignancies. In those affected by an ovarian cancer and carriers of a mutation in the BRCA genes, routine prophylactic surgery should not be considered on the breast, at least in the first 5 years after the diagnosis of ovarian neoplasia. We present the case of a patient with a germinal mutation of the BRCA 1 gene, who debuts with an ovarian cancer, after the study of a neoplastic adenopathy of neck, biopsied in the context of a cutaneous paraneoplastic syndrome.

Nefrectomía radical derecha con resección de trombo tumoral en vena cava inferior nivel III / Right radical nephrectomy with inferior vena cava tumor thrombus level III

INTRODUCCIÓN: El CCR presenta una tendencia conocida a propagarse mediante la formación de trombo tumoral a la vena renal o vena cava inferior (4-10 por ciento ) El nivel que alcanza dicho tumor, está en directa relación con la sobrevida estimada a 5 años. MATERIALES Y MÉTODOS: Se presenta un caso de un paciente de sexo masculino de 58 años de edad, con antecedentes de Dm2 No IR y Tabaquismo crónico, el cual consulto por cuadro de 10 meses de evolución caracterizado por hematuria macroscópica. Dentro de la analítica sanguínea, destacaba paciente anémico, con hemoglobina de 8 g/dL y creatinemia de 1.1mg/mL. Se solicita URO-TAC, evidenciándose tumor renal derecho, de 18 cms en su eje largo, asociado a trombo en vena cava inferior, que se alojaba hasta el diafragma (Nivel III), no observándose metástasis a distancia o adenopatías de aspecto patológico. RESULTADOS: Se propone nefrectomía radical abierta por vía anterior, posteriormente se aísla y controla VCI, la cual se abre en su eje longitudinal. Se realiza trombectomia convencional con cierre primario, verificando hermeticidad del vaso. El tiempo operatorio total fue de 260 minutos, con un sangrado estimado de 1600ml. Se requirió transfusión de 3U de GR intraoperatorios sin incidentes reportados. El manejo post-operatorio inmediato fue en unidad de cuidados intensivos por 24 hrs, con un tiempo hospitalario total de 5 días. El paciente evoluciona favorablemente, sin complicaciones, destacando dentro de los exámenes de control, creatinina de 1.3 mg/dL. A la fecha, no hay evidencia de enfermedad residual clínica, o radiológica. CONCLUSIÓN: La nefrectomía radical convencional con trombo en vena cava inferior (nivel III) es el estándar de tratamiento para pacientes cáncer renal localmente avanzado en condiciones para afrontar la cirugía

INTRODUCTION: CCR presents a known trend to spread by means of a tumor thrombus in renal vein or inferior vena cava (4-10 pertcent ) The level reached by such tumor has a direct relation with the 5-year survival rate. MATERIALS AND METHODS: A 58-year old male patient presented with a history of Dm2 No IR and chronic tabaquism who enquired about 10-month symptoms, characterized by macroscopic hematuria. Amongst the blood analytics, an anemic patient stood out, whose hemoglobin level is 8 g/dL and 1.1mg/mL creatinemia. URO-TAC is requested which shows right kidney tumor, of 18 centimeters on its longer axis, associated to thrombus in the inferior vena cava, extended to the diaphragm (Level III), without presence of distant metastasis or adenopathies with pathological aspect. RESULTS: Anterior open radical nephrectomy is suggested, posteriorly isolated and VCI controlled, which is performed on its longitudinal axis. Conventional thrombectomy with primary closing and verification of vessel hermetism are performed. Operative time was 260 minutes. Estimated blood loss was 1600ml. 3U of GR intraoperative transfusion was required and no incidents were reported. Postoperative management took place in intensive care unit for 24 hours and the patient was discharged 5 days after surgery. The patient evolves favorably, without complications, presenting a 1.3 mg/dL creatinine level. To date, there is no evidence of clinical residual or radiological illness. CONCLUSION: Radical nephrectomy with inferior vena cava thrombus (level III) is the standard treatment for kidney cancer patient presenting local progression in a condition to withstand surgery.

Adenocarcinoma sincrónico de alto grado de endometrio y ovario; a propósito de un caso clínico / Synchronous high-grade adenocarcinoma of the endometrium and ovary; about a clinical case

RESUMEN El cáncer sincrónico endometrial y ovárico (SEOC) representa alrededor de un 5-10% de las neoplasias de endometrio y ovario. Cuando no existe extensión locorregional y presentan un patrón histológico de bajo grado, actúan como si fueran dos tumores primarios independientes, en lugar de comportarse como un cáncer en estadio avanzado. Los mecanismos para diferenciar si su origen es metastásico o por el contrario, son tumores primarios independientes conlleva una gran dificultad y ha generado una importante controversia dentro del estudio de este tipo de neoplasias. En este artículo, exponemos el caso clínico de una paciente de 46 años que presenta un tumor sincrónico de endometrio y ovario en estadio IA, desconocido hasta el estudio histológico de la pieza quirúrgica.

ABSTRACT Endometrial and ovarian synchronous cancer (SEOC) accounts for about 5-10% of endometrial and ovarian neoplasms. When there is no local extension and they present a low-grade histological pattern, they act as if they were two independent primary tumours, instead of behaving as an advanced stage cancer. Therefore, the differentiation of its origin (metastatic or independent primary tumours) is fraught with difficulty and has generated a significant controversy in the study of this type of neoplasms. In this article, we present the clinical case of a 46-year-old patient presenting a synchronous tumor of the endometrium and ovary in IA stage, unknown until the histological study of the surgical sample.

Mioma vaginal intraabdominal, masa pélvica de localización atípica / Intra-abdominal vaginal myoma, a pelvic mass of atypical location

La patología miomatosa del tracto genital inferior es uno de los motivos más frecuentes de consulta en Ginecología. Sin embargo, su localización vaginal resulta una situación infrecuente de difícil diagnóstico. En muchas ocasiones se lleva a cabo tras un hallazgo casual intraoperatorio. Las manifestaciones clínicas que producen los leiomiomas en esta localización son inespecíficas; el tratamiento quirúrgico es el de elección, generalmente mediante un abordaje por la vía vaginal(AU)

Myomatous disease of the lower genital tract is one of the most common reasons for gynecological consultation. However, vaginal location is infrequent and difficult to diagnose. On many occasions diagnosis is based on a fortuitous intraoperative finding. The clinical manifestations of vaginal leiomyomas are unspecific. Surgery is the treatment of choice, which is generally performed by vaginal approach(AU)

Metástasis ovárica única de angiosarcoma mamario como localización infrecuente / Single ovarian metastases of breast angiosarcoma as unusual location

Los angiosarcomas son tumores vasculares extremadamente raros con alta tasa de proliferación e invasión. Están caracterizados por células anaplásicas que se originan en las paredes de los vasos sanguíneos. Poseen mal pronóstico debido a su comportamiento altamente agresivo, el cual condiciona una elevada probabilidad de recurrencia local y extensión multiorgánica. Se presentan principalmente en: pulmón, hígado, ganglios linfáticos y huesos. Su tratamiento es controvertido debido escasa casuística disponible acerca de esta estirpe tumoral, aunque parece claro que el tratamiento principal es la cirugía y que el tratamiento posterior puede ser la quimioterapia adyuvante(AU)

Angiosarcomas are extremely rare vascular tumors with high rate of proliferation and invasion. They are characterized by anaplastic cells originating in the walls of blood vessels. They have poor prognosis because of their highly aggressive behavior, which determines a high probability of local recurrence and spreading to multiple organs. They occur mainly in lung, liver, lymph nodes and bones. Treatment is controversial due to small number of cases available about this tumor type, although it seems clear that the main treatment is surgery and subsequent treatment can be adjuvant chemotherapy(AU)

La melatonina reduce la respuesta de cortisol al ACTH en humanos / Melatonin reduces cortisol response to ACTH in humans

Background: Melatonin receptors are widely distributed in human tissues but they have not been reported in human adrenal gland. Aim: To assess if the human adrenal gland expresses melatonin receptors and if melatonin affeets cortisol response to ACTH in dexamethasone suppressed volunteers. Material and methods: Adrenal glands were obtained from 4 patients undergoing unilateral nephrectomy-adrenalectomy for renal cáncer. Expression of mRNA MT1 and MT2 melatonin receptors was measured by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR). The effect of melatonin on the response to intravenous (i.v.) ACTH was tested (randomized cross-over, double-blind, placebo-controlled tríal) in eight young healthy males pretreated with dexamethasone (1 mg) at 23:00 h. On the next day at 08:00 h, an i.v. Une was inserted, at 08:30 h, and after a blood sample, subjeets ingested 6 mg melatonin or placebo. At 09:00 h, 1-24 ACTH (Cortrosyn, 1µg/1.73 m² body surface área) was injected, drawing samples at 0, 15, 30, 45 and 60 minutes after. Melatonin, cortisol, cortisone, progesterone, aldosterone, DHEA-S, testosterone and prolactin were measured by immunoassay. Results: The four adrenal glands expressed only MT1 receptor mRNA. Melatonin ingestión reduced the cortisol response to ACTH from 14.6+1.45µg/dl at 60 min in the placebo group to 10.8+1.2µg/dl in the melatonin group (p <0.01 mixed model test). It did not affect other steroid hormone levels and abolished the morningphysiological decline of prolactin. Conclusions: The expression ofMTl melatonin receptor in the human adrenal, and the melatonin reduction of ACTH-stimulated cortisol production suggest a direct melatonin action on the adrenal gland .

Carcinoma de células transicionales del tracto urinario superior: opciones de tratamiento actual y abordajes mínimamente invasivos / Upper urinary tract transitional cell carcinoma: current treatment overview of minimally invasive approaches

Las indicaciones para el manejo mínimamente invasivo de los tumores del tracto urinario superior están en constante expansión. El desarrollo de equipamiento endoscópico cada vez más sofisticado ha llevado a un cambio en la práctica diaria y a una tendencia al manejo conservador. Nuestro objetivo es revisar las diferentes opciones de manejo mínimamente invasivo para el manejo de los tumores del tracto urinario superior, con énfasis en laparoscopia, ureteroscopia y cirugía percutánea.

The indications for minimally invasive treatment for are expanding. The development of more sophisticated endoscopic equipment has led to changes in everyday practice and a trend towards more conservative management. Our objective is to make a review of the different options for management UUT-TCC, with emphasis in laparoscopy, ureteroscopy and percutaneous surgery.

El tamaño de los tumores suprarrenales ¿está en relación al tiempo de evolución o expresa una diferencia biológica? / Is adrenal tumor size related to evolution time or does it represent a biological difference?

Background: Adrenal tumor (AT) malignancy has been related to tumor size. Since laparoscopic surgery is being used, smaller adrenal tumors are being excised. Aim: To evaluate eventual clinical and histológica! differences between adrenal tumors smaller than 4 cm. and those larger than 6 cm. Patients and Methods: Retrospective review of pathological reports and clinical records of patients operated for adrenal tumors, dividing them in two groups. Group 1 had 29patients aged 52 ± 13 years with AT < 4 cm operated during the period 2000-2005, and Group 2 was formed by 52 patients aged 46 ±18 years with AT >6 cm operated between 1984-2005- Tumors between 4 and 6 cm were not included in the study to establish clear cut differences between groups. Results: Tumors were functional in 40 and 41 percent of cases in groups 1 and 2 respectively. Fifty percent of functional tumors of group 1 were pheochromocytomas and the rest secreted aldosterone. In group 2, 66 percent of tumors were phechromocytomas and no aldosterone secreting tumors were found. Fifty two and eight percent of tumors in Groups 1 and 2 were adenomas, respectively (p <0.001). Nineteen tumors of group 2 were malignant, compared with one of group 1 (p <0.001). Conclusions: The tumor size of adrenal cortical tumors may represent biological differences, suggesting two different tumor populations. At time of diagnosis adrenal carcinomas are almost always larger than 6 cm.

El neurocitoesqueleto: un nuevo blanco terapéutico para el tratamiento de la depresión

resumen está disponible en el texto completo

Summary Postmortem and neuroimaging studies of Major Depressive Disorder patients have revealed changes in brain structure. In particular the reduction in prefrontal cortex and in hippocampus volume has been described. In addition, a variety of cytoarchitectural abnormalities have been described in limbic regions of major depressive patients. Decrease in neuronal density has been reported in the hippocampus, a structure involved in declarative, spatial and contextual memory. This structure undergoes atrophy in depressive illness along with impairment in cognitive function. Several studies suggest that reduction of hyppocampus volume is due to the decreased cell density and diminished axons and dendrites. These changes suggested a disturbance of normal neuronal polarity, established and maintained by elements of the neuronal cytoskeleton. In this review we describe evidence supporting that neuronal cytoskeleton is altered in depression. In addition, we present data indicating that the cytoskeleton can be a potential target in depression treatment. Neurons are structural polarized cells with a highly asymmetric shape. The cytoskeleton plays a key role in maintain the structural polarization in neurons which are differentiated in two structural domains: The somato-dendritic domain and the axonal domain. This differentiated asymmetric shape, depends of the cytoskeletal organization which support, transport and sorts various molecules and organelles in different compartments within the cell. Microtubules determine the asymmetrical shape and axonal structure of neurons and form the tracks for intracellular transport, of crucial importance in axonal flux. Actin microfilaments are involved in force generation during organization of neuronal shape in cellular internal and external movements and participate in growth cone formation. This important cytoskeletal organization preceed the formation of neurites that eventually will differentiated into axons or dendrites, a process that also comprises a dynamic assembly of the three cytoskeletal components. Intermediate filaments are known in neurons as neurofilaments spatially intercalated with microtubules in the axons and facilitate the radial axonal growth and the transport. Neurofilaments also act supporting other components of the cytoskeleton. All changes and movements of the cytoskeletal organization are coordinated by cytoskeletal associated proteins such as the protein tau and the microtubule associated proteins (MAPs). Also, specific interactions of microfilaments, microtubules and filaments which are regulated by extracellular signals take place in modulation of the cytoskeletal rearrangements. The polarized structure and the highly asymmetric shape of neurons are essentials for neuronal physiology and it appears to be lost in patients with a Major Depressive Disorder. Histopathological studies have shown that the hippocampus and frontal cortex of patients with major depressive disorder have diminished soma size, as well as, have decreased dendrites and cellular volume. Dendrite formation depends mainly in microfilaments organization as well as in polarization of the microtubule binding protein MAP2. In addition, there is a decreased synaptic connectivity and an increased oxidative stress, which originates abnormalities in the cytoskeletal structure. These neuronal changes originate alterations in the brain functionality such as decreased cognitive abilities and affective dis-regulations, usually encountered in patients with depression. Therefore, pathologic lesions implicating an altered cytoskeletal organization, may have an important role in decreased cognitive functions, observed in depression, as well as in changes in the brain volume, explained by a lost of neuronal processes such as axons, dendrite processes or dendritic spines, rather than by loss of neuronal or glial cell bodies. This explanation is supported by light immunomicroscopy of brain slices postmortem stained with specific antibodies. Psychological stress which causes oxidative stress has also been suggested to cause a decrease of neuronal volume in the prefrontal cortex, altering the synaptic connections established with the hippocampus. This conclusion was drawn from studies in animal models of psychological stress associated with molecular measurements where defects in the expression of MAP1 and sinaptophysin were found, suggesting that defects in cytoskeletal associated proteins could underlie some cytoarchitectural abnormalities described in depression. Together all the evidence accumulated indicates that major depression illness and bipolar depression are mental disorders that involve loss of axons and dendrites in neurons of the Central Nervous System, that in consequence cause disruption of synaptic connectivity. Thus is possible that depression can be considered as a cytoskeletal disorder, therefore this cellular structure could be a drug target for therapeutic approaches by restoring normal cytoskeleton structure and precluding damage caused by oxygen-reactive species. In this regard, melatonin, the hormone secreted by pineal gland during dark phase of the photoperiod, has two important properties that can be useful in treatment of mental disorders. First, the melatonin is a potent free-radical scavenger and second this hormone governs the assembly of the three main cytoskeletal components modulating the cytoskeletal organization. This notion is supported by direct action of melatonin effects on cytoskeletal organization in neuronal cells. In N1E-115 neuroblastoma cells, melatonin induced a two-fold increase in number of cells with neurites 1 day after plating; the effect lasting up to 4 days. Induction of neurite outgrowths is optimal at 1 nM melatonin and in presence of hormone the cells grew as clusters with long neurites forming a fine network to make contact with adjacent cells. Immunofluorescence of N1E-115 cells cultured under these conditions showed tubulin staining in long neurite processes connecting cells to each other. Neurite formation is a complex process that is critical to establish synaptic connectivity. Neuritogenesis takes place by a dynamic cytoskeletal organization that involves microtubule enlargement, microfilament arrangement, and intermediate- filament reorganization. In particular, it is known that vimentin intermediate filaments are reorganized during initial stages of neurite outgrowth in neuroblastoma cells and cultured hippocampal neurons. Evidence has been published indicating that increase in microtubule assembly participates in neurite formation elicited by melatonin antagonism to calmodulin. Moreover, recently it was reported that melatonin precludes cytoskeletal damage produced by high levels of free radicals produced by hydrogen peroxide, as well as, damage caused by higher doses of the antypsychotics haloperidol and clozapine. N1E-115 cells incubated with either 100 uM hydrogen peroxide, 100 uM haloperidol, or 100 uM clozapine undergo a complete cytoskeletal retraction around the nucleus. By contrast, NIE-115 cells incubated with hydrogen peroxide, clozapine, or haloperidol followed by the nocturnal cerebrospinal fluid concentration of melatonin (100 nM) showed a well preserved cytoskeleton and neuritogenesis. Thus melatonin is a neuroprotective compound, since protects the neurocytoskeletal organization against damage caused by high concentrations of antipsychotics and oxidative stress. As mentioned previously, polarity is intrinsic to neuronal function. In neurons, somatodendritic domain receives and decodes incoming information and axonal domain delivers information to target cells. Progressive loss of neuronal polarity is one of the histopathologic events in depression. Cytoskeletal collapse underlie the lost of structural polarity and it is known that precede neuronal death and disappearance of synaptic connectivity. Drugs that prevent the loss of polarity and cytoskeleton retraction intrinsic to these diseases, as well as damage in cytoskeletal structure produced by oxidative stress can be extremely useful in depression treatment. Melatonin is a potent free-radical scavenger that also acts as a cytoskeleton regulator; thus, we speculate that this hormone could be useful in prevention and alleviation of psychiatry diseases with synaptic connectivity disruption. Clinical trials show that melatonin administration is followed by alleviation of circadian disturbances and cognitive function in various neuropsychiatry diseases. Moreover, in depression, melatonin improves sleep. Thus, as suggestive as this information appears, controlled clinical trials will be necessary to investigate the beneficial effects of melatonin and other drugs in the depression treatment.

Tumores renales quísticos, correlación clínico patológica y sobrevida / Cystic renel tumours, pathological correlation and survival

El aumento de utilización de imágenes diagnósticas en los últimos años para la evaluación de síntomas abdominales inespecíficos ha aumentado el hallazgo de masas renales asintomáticas. Entre 4 a 12 por ciento de los cánceres renales, corresponde a lesiones quísticas. Se han realizado múltiples estudios descriptivos, siendo el tratamiento de estas lesiones, aún tema en discusión. Objetivos: Los objetivos de este trabajo son: 1) evaluar la correlación de imágenes de tumores renales quísticos, con los resultados en la anatomía patológica; 2) evaluar los resultados y sobrevida en pacientes con cáncer renal quístico y 3) comparar su evolución y pronóstico con un grupo de pacientes con cáncer renal sólido. Materiales y Métodos: Se realizó una revisión retrospectiva de pacientes tratados en el Servicio de Urología del Hospital de la Pontificia Universidad Católica de Chile, por sospecha de cáncer renal quístico, entre los años 1999 y 2005. Los pacientes fueron tratados con nefrectomía parcial o radical. Para ello se evaluaron los datos clínicos, evolución y seguimiento de los enfermos. Se comparó etapa, grado de Fuhrman y sobrevida con un grupo de 47 pacientes con cáncer renal sólido, pareados por edad y sexo. Resultados: La serie está compuesta de 51 pacientes, 4 de los cuales, resultaron ser lesiones benignas. De los pacientes que presentaron cánceres renales quísticos (47 pacientes), la edad promedio de presentación fue de 57 años DE 12,3 (30-84). La distribución por sexo fue 72 por ciento hombres y 28 por ciento mujeres. Las formas de presentación fueron: 72,3 por ciento hallazgo por imágenes, 10,6 por ciento dolor abdominal, 6,3 por ciento hematuria, 2,1 por ciento masa palpable y 2,1 por ciento hematuria asociado a dolor. El tamaño tumoral promedio al TAC y anatomía patológica fue 5,4 y 4,9 cm, respectivamente. A los pacientes, se les realizó nefrectomía radical (57 por ciento) y parcial (43 por ciento). El alta quirúrgica fue en promedio a los 6,1 días. Histología: 92 por ciento carcinoma de células renales, variedad células claras, 4 por ciento mixto (células claras y papilar), 2 por ciento liposarcoma mixoideo de grasa perinefrítica y 2 por ciento indiferenciado...