Chronic inhalation of 2, 2-dichlorovinyl dimethyl phosphate (DDVP) induces organ pathology in the adult albino rats

The acute toxic effects of the acetyl cholinesterase-inhibiting pesticide, DDVP, following oral and dermal exposure are well recorded in literature. The ability of DDVP to easily vaporize makes the aero-nasal route a possible means of exposure, albeit chronically. This study aimed to describe the pathology, if any, of the heart, kidney and liver following chronic exposure to various concentrations of DDVP via inhalation.Sixty male Wistar rats were divided into 6 groups (A-F) of 10 rats each. Rats in Group A were exposed to distilled water only, while rats in groups B, C, D, E and F were exposed to 20, 40, 60, 80 and 100% v/v concentrated fumes of DDVP respectively. Duration of inhalational exposure was for 90 days. The heart, liver and kidney of the rats in the groups were extracted for routine histopathology. Organ pathologies were semi-quantitatively scored and analyzed across and between the 6 groups.Generally, lesions were of progressive severity with increasing concentrations of DDVP. Across the organs, pathology was related to altered vascular and degenerative changes. Specifically, the heart, kidney and liver showed shredding of cardiomyocytes, sloughing of renal tubular epithelial cells with dilated tubular lumina, and hepatocellular degeneration and necrosis respectively. Inflammatory changes were limited to the livers of rats exposed to 80 and 100% v/v DDVP.It was concluded that DDVP induced altered vascular and degenerative changes following chronic exposure via inhalation. Safer alternatives to aerosolized DDVP-containing insecticides are recommended for the control of arthropod vectors in enclosures

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Ictericia obstructiva secundaria a adenoma en conducto hepático común / Obstructive jaundice caused by an adenoma of the common hepatic duct

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Esteatohepatitis no alcohólica y adenomatosis hepática: ¿asociación casual o causal? / Nonalcoholic steatohepatitis and hepatic adenomatosis: casual or causal relationship?

La adenomatosis hepática es una enfermedad benigna definida por la aparición de múltiples adenomas en un hígado normal. Se trata de una entidad poco frecuente y de causa no conocida, de la que existen menos de un centenar de casos publicados en la literatura médica y que se ha relacionado con la toma de anticonceptivos orales o esteroides anabolizantes, con enfermedades por depósito y con mutaciones genéticas asociadas a la diabetes mellitus tipo MODY (maturity onset diabetes of the young). En los últimos años se ha comunicado la coexistencia de adenomatosis hepática con lesiones de esteatohepatitis no alcohólica en dos pacientes con síndrome metabólico, una asociación de interés por la creciente prevalencia de la enfermedad hepática grasa no alcohólica en los países desarrollados y por la posibilidad de que compartan un mecanismo causal. Comunicamos el caso de una mujer joven con fructosemia familiar y esteatosis hepática durante cuyo seguimiento aparecieron múltiples adenomas hepáticos asociados a lesiones de esteatohepatitis y discutimos el posible significado de dicha asociación (AU)

Hepatic adenomatosis is a benign disease defined as the presence of multiple adenomas in a normal liver. It is an uncommon condition and there are less than a hundred reported cases in the literature. The etiology is unknown, although it has been associated with the use of oral contraceptives, anabolic steroids, certain storage diseases and some genetic mutations linked to maturity onset diabetes of the young. The coexistence of hepatic adenomatosis and nonalcoholic steatohepatitis has been recently described in two patients suffering from metabolic syndrome. This association is particularly interesting due to the growing prevalence of nonalcoholic fatty liver disease in developed countries and the possibility of a common causal pathway. We report the case of a young woman with fructosemia and hepatic steatosis; multiple hepatic adenomas associated to steatohepatitis lesions were also found during clinical follow-up. The possible implications are discussed (AU)

Adenoma hepático malignizado en varones: presentación de 2 casos / Malignant liver adenoma in men: report of 2 cases

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Expression of serum miR-218 in hepatocellular carcinoma and its prognostic significance

Background: Several recent studies have revealed that microRNAs (miRNAs) are stably detectable in the circulation and can be used as biomarkers for diagnosis and prognosis of malignancy. The aim of this manuscript is to investigate serum miR-218 expression in patients with hepatocellular carcinoma (HCC) and to analyze its potential diagnostic and prognostic value in HCC. Methods: Quantitative real-time quantitative PCR (qPCR) was conducted to detect serum miR-218 expression from 156 HCC and 98 benign liver diseases (BLD) as well as 64 healthy controls. The relevance of serum miR-218 expression to the clinicopathological factors was assessed. In addition, the prediction of cutoff values of the markers was performed by the receiver operating characteristic (ROC) curve. Moreover, the Kaplan-Meier method was used to plot survival curves and univariable and multivariable Cox regression analyses were used to evaluate independent prognostic factors. Results: Consequently, our findings revealed that serum miR-218 levels were remarkably underexpressed in HCC patients as compared to BLD patients and healthy controls. And its low level was obviously related to tumor size (p = 0.048), tumor number (p = 0.018), vascular invasion (p = 0.039), Edmondson grade (p = 0.042), and higher TNM stage (III-IV). ROC curve analysis showed that miR- 218 had a significant diagnostic accuracy, yielded an AUC (the areas under the ROC curve) of 0.734 (95 % confidence interval (CI) 0.68-0.789, p < 0.01), thus providing a sensitivity of 66.7 % and a specificity of 69.1 % in discriminating HCC from BLD and healthy controls. Meanwhile, miR-218 can act as a useful biomarker in distinguishing the patients with large tumors (>5 cm) from patients with small tumors (<5 cm) (p < 0.01). In addition, the combination of miR-218 and AFP had greater diagnosis capacity with an AUC of 0.908 (95 % CI 0.876-0.940; p < 0.01). Both log-rank test and Cox regression analysis demonstrated that the decreased serum expression of miR-218 had a significant impact on overall survival of the patients with HCC (HR = 3.049, 95 % CI 2.028-4.585, p < 0.01). Conclusion: Taken together, this study suggested that serum expression of miR-218 might be a potential noninvasive tumor biomarker in the diagnosis and assessment of prognosis of HCC

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Esteatosis hepática focal multinodular / Multinodular focal hepatic steatosis

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Estudio multicéntrico sobre adenomas hepáticos / Multicentre study on hepatic adenomas

INTRODUCCIÓN: El adenoma hepático (AH) es un tumor benigno que puede presentar graves complicaciones por lo que, clásicamente, todos eran resecados. Actualmente se ha demostrado que los menores de 3 cm, y si no expresan Beta -catenina, solo se complican excepcionalmente, lo que ha cambiado la estrategia terapéutica. MATERIAL Y MÉTODOS: Estudio retrospectivo en 14 unidades HPB. Criterio de inclusión: pacientes con AH resecado y confirmado histológicamente. Periodo de estudio: 1995-2011. RESULTADOS: Fueron intervenidos 81 pacientes. Edad: 39,5 años (rango: 14-75). Sexo: mujeres (75%). Consumo de estrógenos en mujeres: 33%. Tamaño: 8,8 cm (rango: 1-20 cm). Solo 6 AH (7,4%) eran menores de 3 cm. La mediana de AH fue 1 (rango: 1-12). Nueve pacientes presentaban adenomatosis (> 10 AH). El 51% de los pacientes presentaban síntomas; el más frecuente (77%) era dolor abdominal. Ocho pacientes (10%) comenzaron con abdomen agudo por rotura o hemorragia. El 67% de los diagnósticos preoperatorios fueron correctos. La cirugía fue programada en el 90% de los pacientes. Las técnicas fueron: hepatectomías mayores (22%), menores (77%) y un trasplante hepático. Un 20% fueron realizadas por laparoscopia. La morbilidad fue 28%. No hubo mortalidad. Tres pacientes presentaron malignización (3,7%). El seguimiento fue 43 meses (rango: 1-192). Se detectaron 2 recidivas que fueron resecadas. DISCUSIÓN: Los pacientes con AH resecados son habitualmente mujeres con lesiones grandes, con un consumo de estrógenos inferior al esperado. Su diagnóstico preoperatorio correcto es aceptable (70%). La tasa de hepatectomías mayores es 25% y la de laparoscopia, 20%. Hemos obtenido una baja morbilidad y nula mortalidad

INTRODUCTION: Hepatic adenomas (HA) are benign tumours which can present serious complications, and as such, in the past all were resected. It has now been shown that those smaller than 3 cm not expressing Beta-catenin only result in complications in exceptional cases and therefore the therapeutic strategy has been changed. MATERIAL AND METHOD: Retrospective study in 14 HPB units. Inclusion criteria: patients with resected and histologically confirmed HA. Study period: 1995-2011. RESULTS: 81 patients underwent surgery. Age: 39.5 years (range: 14-75). Sex: female (75%). Consumption of oestrogen in women: 33%. Size: 8.8 cm (range, 1-20 cm). Only 6 HA (7.4%) were smaller than 3 cm. The HA median was 1 (range: 1-12). Nine patients had adenomatosis (> 10HA). A total of 51% of patients displayed symptoms, the most frequent (77%) being abdominal pain. Eight patients (10%) began with acute abdomen due to rupture and/or haemorrhage. A total of 67% of the preoperative diagnoses were correct. Surgery was scheduled for 90% of patients. The techniques employed were: major hepatectomy (22%), minor hepatectomy (77%) and one liver transplantation. A total of 20% were performed laparoscopically. The morbidity rate was 28%. There were no cases of mortality. Three patients had malignisation (3.7%). The follow-up period was 43 months (range 1-192). Two recurrences were detected and resected. DISCUSSION: Patients with resected HA are normally women with large lesions and oestrogen consumption was lower than expected. Its correct preoperative diagnosis is acceptable (70%). The major hepatectomy rate is 25% and the laparoscopy rate is 20%. There was a low morbidity rate and no mortality

Clasificación inmunofenotípica de 3 casos de adenomas hepatocelulares. Diagnóstico diferencial con hiperplasia nodular focal / Immunophenotypic classification of 3 cases of hepatocellular adenoma. Differential diagnosis with focal nodular hyperplasia

El descubrimiento de los cambios moleculares de los adenomas ha dado lugar a un renovado interés en este tipo de tumor. En la última edición de la OMS de los tumores del tracto gastrointestinal (2010) se incluyen 4 tipos de adenomas hepáticos, bien caracterizados inmunohistoquímicamente, genotípicamente y fenotípicamente, en los que tienen un papel importante los antecedentes clínicos y su comportamiento morfológico para determinar el posterior riesgo de malignidad, fundamentalmente en aquellos con mutación de la b-catenina. La presencia de esteatosis, inflamación y cambios vasculares, unidos a la respuesta frente a la FABP, el amiloide sérico A y la glutamina sintetasa nos permite clasificarlos en 4 grupos: con mutación de HNF1A (H-HCA), con mutación de b-catenina (b-HCA), inflamatorios (IHCA) y sin marcadores. La ausencia de expresión frente al glypican 3, el HSP 70 y el mapeo perivenular frente a la glutamina sintetasa ayuda a excluirlos frente a los hepatocarcinomas bien diferenciados. En este trabajo describimos el comportamiento clínico, morfológico e inmunofenotípico de 3 casos de pacientes diagnosticados de adenomas hepáticos en un período de 2 años (AU)

Interest in adenomas has been renewed by the discovery of the molecular changes in these tumors. The latest World Health Organization publication on gastrointestinal tract tumors (2010) includes four types of hepatic adenomas, which are well characterized immunohistochemically, genotypically and phenotypically. In these tumors, medical history and morphological behavior play an important role in determining the risk of malignancy, mainly in adenomas with a b-catenin mutation. The presence of steatosis, inflammation, vascular changes linked to response to L-FABP, serum amyloid A, and glutamyl synthetase help to classify these tumors into four groups: hepatocellular adenomas with the HNF1A mutation (H-HCA), those with the b-catenin mutation (b-HCA), inflammatory HCA (IHCA), and HCA without markers. The absence of glypican 3 expression, HSP 70 and perivenular mapping of glutamyl synthetase helps to distinguish these tumors from well differentiated hepatocellular carcinoma. We describe the clinical, morphological and immunophenotypic features of three patients diagnosed with hepatic adenomas in a 2-year period (AU)

Solución del caso 34. Adenoma hepático / Solution to case 34. Adenoma of the liver

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Hemorragia como forma de presentación de un adenoma hepático gigante / Hemorrhaging as a presentation form of giant hepatic adenoma

Se describe el caso de un adenoma hepático de gran tamaño que debutó con hemorragia, dolor abdominal y fiebre de varios días de evolución. Se enumeran algunas entidades que puedan estar asociadas al adenoma hepático. Se enfatiza en las pruebas de imagen como métodos para un diagnóstico correcto, que debe confirmarse con el estudio anatomopatológico (AU)

We describe the case of a teenager with a large hepatic adenoma who presented with bleeding, abdominal pain and fever for some days. Some entities may be associated with hepatic adenoma. Emphasis is placed on imaging test as methods for a correct diagnosis, which must be confirmed by pathological study (AU)

Mujer de 41 años con insuficiencia renal y masa hepática / A 41 year old woman with renal insufficiency and a mass in the liver

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Trasplante hepático en pacientes con lesiones hepáticas benignas / Liver transplantation in patients with benign hepatic lesions

Las lesiones benignas hepáticas son enfermedades poco frecuentes y el trasplante hepático en ellas es excepcional. Presentamos una revisión del tema, con comentarios sobre las entidades subsidiarias de trasplante hepático, de las que destacan: la adenomatosis, la poliquistosis y el hemangioendotelioma epitelioide hepático (aunque este proceso sea de grados bajo a intermedio de malignidad). Valoramos aspectos específicos de estas lesiones, desde el punto de vista epidemiológico, etiopatogénico, clínico, diagnóstico, terapéutico, indicación del trasplante y experiencia de los diferentes autores en estas afecciones (AU)

Benign hepatic lesions are rare and liver transplantation in these cases is exceptional. We present a review of the subject, commenting on the aspects that have been subsidiary to liver transplantation, of which are highlighted: adenomatosis, polycystosis and hepatic epithelioid haemangioendothelioma (although this process may be a low to intermediate malignant grade). We assessed specific epidemiological, aetiopathogenic, clinical, diagnostic, therapeutic and aspects of the lesions as well as indication for transplantation, and the experiences of different authors on these pathologies (AU)

Adenomatosis hepática / Hepatic adenomatosis

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Captación de 123I-MIBG (metayodobencilguanidina) en un adenoma hepático / 123I-MIBG scintigraphy uptake in a hepatic lesion

El feocromocitoma es un tumor derivado de las células cromafines de la médula adrenal. Cuando afecta a células situadas en la cadena simpática, se denomina paraganglioma. Pese a ser infrecuente, debe incluirse entre las posibles causas de hipertensión, arritmias cardíacas y crisis de ansiedad. Presentamos el caso de una mujer con un feocromocitoma vesical y una lesión hepatocelular con captación positiva en el estudio isotópico con MIBG (metayodobencilguanidina) que se ha interpretado como un falso positivo El mielolipoma adrenal es un tumor benigno, poco frecuente, compuesto por tejido adiposo maduro y elementos hematopoyéticos diversos. Su hallazgo suele ser incidental, aunque en ocasiones pueden alcanzar gran tamaño y causar dolor abdominal y otros síntomas clínicos. La ecografía y la tomografía computarizada son herramientas útiles en su diagnóstico. Los tumores pequeños (< 6 cm) y asintomáticos pueden tratarse de forma conservadora con vigilancia periódica y los > 6 cm o con síntomas pueden precisar tratamiento quirúrgico. Presentamos un caso de mielolipoma adrenal gigante y a continuación se realiza una revisión de la literatura (AU)

Pheochromocytoma is a tumor derived from the chromaffin cells of the adrenal medulla. When this type of tumor involves the sympathetic ganglia it is called paraganglioma. Although infrequent, paraganglioma should be considered in the evaluation of hypertension, arrhythmias, and panic disorder. We report the case of a woman with bladder pheochromocytoma and a hepatic lesion. MIBG scintigraphy showed non-physiological uptake, which was interpreted as a false positive result (AU)

Hemoperitoneo como forma de presentación del carcinoma hepatocelular: experiencia de tres casos con rotura tumoral espontánea y revisión de la literatura / Hemoperitoneum as presentation of hepatocellular carcinoma: experience in three cases with spontaneous tumoral rupture and review of the literature

El hemoperitoneo secundario a la rotura espontánea de un carcinoma hepatocelular (CHC) supone una complicación potencialmente fatal en ausencia de un abordaje terapéutico apropiado. Constituye una forma de presentación tumoral bien establecida en medios con elevada incidencia de CHC, pero resulta infrecuente en países occidentales, donde se describe en menos del 5% de los casos. Presentamos tres pacientes atendidos en nuestro centro por hemoperitoneo agudo secundario a la rotura no traumática de un CHC, en los que dicha complicación constituyó la primera manifestación del proceso neoplásico. Realizamos igualmente una revisión de la literatura relacionada con el tema

Hemoperitoneum due to spontaneous rupture of hepatocellular carcinoma (HCC) constitutes a life-threatening situation if no appropriate therapy is provided. This complication is a well-known form of HCC presentationin countries with high incidence of liver tumours, but is an unusual event in Western countries, where it has been described in 5% or less of cases with HCC. We report three patients admitted to our centre with acute hemoperitoneum secondary to non-traumatic rupture as a first manifestation of not previously diagnosed HCC. A review of the related literature is also performed

Amiloidosis secundaria (AA) asociada a tumoraciones benignas / Systemic AA amyloidosis induced by benign neoplasms

La amiloidosis se caracteriza por el depósito de proteínas de características ultraestructurales fibrilares, con plegamiento Beta en capas e insolubles, que se depositan mayoritariamente a nivel de los espacios extracelulares de órganos y tejidos. Se clasifica típicamente según la naturaleza bioquímica de la proteína fibrilar, y según su distribución en el organismo podrá ser sistémica o localizada. La amiloidosis sistémica más frecuente en la práctica clínica es la denominada AL (idiopática primaria o asociada a mieloma múltiple) cuyas fibrillas están formadas por cadenas ligeras. En cambio, la amiloidosis AA (secundaria, reactiva o adquirida) es aquella que se desarrolla típicamente como complicación de una enfermedad inflamatoria crónica, destacando entre las más habituales; enfermedades de origen reumatológico (artritis reumatoide, espondilitis anquilopoyética, artritis psoriásica), la fiebre mediterránea familiar, la enfermedad inflamatoria intestinal, así como infecciones cronificadas (tuberculosis, osteomielitis). No obstante, otras causas responsables de su desarrollo y en muchas ocasiones infravaloradas, son las tumoraciones benignas. Algunas de estas entidades, también tendrán capacidad de actuar como estímulo responsable de la formación de estas proteínas, que finalmente se depositarán en diferentes tejidos del organismo. Es importante resaltar, que el diagnóstico precoz así como el tratamiento eficaz de la enfermedad subyacente ha permitido disminuir su incidencia, así como en algunos casos incluso revertirla. Aquí, presentamos dos casos clínicos paradigmáticos de tumoraciones benignas, adenoma hepático y Enfermedad de Castlemann, que desarrollaron posteriormente amiloidosis AA con afectación renal principalmente en forma de síndrome Nefrótico (AU)

Amyolidosis is a systemic disorder characterized by the extracellular tissue deposition of insoluble, toxic aggregates in bundles of Beta-sheet fibrillar proteins. These deposits are typically identified on the bases of their apple-green birrefringence under a polarized light microscope after staining with Congo red, and by the presence of rigid, non branching fibrils 8 to 10 nm in diameter on electron microscopy. The type of amyloid fibril unit can be further defined by immunohistology or by immunoelectron microscopy. It has been described at least 25 different human protein precursors of amyloid fibrils, which will describe its corresponding amyloid disease. The most common types of amyloidosis are AL (primary) and AA (secondary) types; the former, is the most frequent and is due to deposition of proteins derived from immunoglobulin light chain fragments, occurring alone or in association with multiple myeloma. The later (AA), is caused by deposition of fibrils composed of fragments of the acute phase reactant serum amyloid A (SAA) and complicates chronic diseases with ongoing or recurring inflammation, namely; rheumatoid arthritis (RA), juvenile chronic polyarthritis, ankylosing spondylitis, familial periodic fever syndromes (Familial Mediterranean Fever), chronic infections and furthermore, some neoplasms (mainly renal cell carcinoma and Hodking¿s disease). Despite its less frequent association, some benign neoplasms can subsequently complicate to AA amyloidosis, therefore, an early diagnose and successful treatment may lead indeed, to regression of the amyloid disease. Herein, we present two cases of AA amyloidosis, both of them caused by 2 different benign neoplasms: 1. A 34 year-old woman, after chronic oral contraceptive use, developed an hepatic adenoma (fig. 1) which finally lead to AA amyloidosis with primary kidney presentation (pure nephrotic syndrome) (table 1). Post-surgical complications yield to acute renal failure from which unfortunately could not be recovered. After being on hemodialysis therapy during 10 months she received a first renal allograft without any complication. 2. A 20 yearold woman, was diagnosed of AA amyloidosis after a renal biopsy (fig. 2) because of nephrotic syndrome (table 1). Further investigation lead to the finding of a hialyne-vascular type Castleman¿s disease located in the retroperotoneum (fig. 2). Despite surgical resection and medical treatment (colchicine) she developed progressive renal failure requiring initialization of hemodialysis therapy. After 6 years being on hemodialysis, she received a first renal allograft which is currently functioning after one year of follow- up. Although other chronic inflamatory diseases complicate more frequently to AA amyloidosis, benign tumors have to be taken into account as a potential ethiological cause for secondary amyloidosis (AU)

Indicaciones controvertidas de trasplante hepático: tumores primarios distintos del hepatocarcinoma y metástasis hepáticas / No disponible

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