A phase I clinical trial of thymidine kinase-based gene therapy in advanced hepatocellular carcinoma.

The aim of this phase I clinical trial was to assess the feasibility and safety of intratumoral administration of a first-generation adenoviral vector encoding herpes simplex virus thymidine kinase (HSV-TK) gene (Ad.TK) followed by systemic ganciclovir to patients with advanced hepatocellular carcinoma (HCC). Secondarily, we have analyzed its antitumor effect. Ten patients were enrolled in five dose-level cohorts that received from 10¹° to 2 × 10¹² viral particles (vp). Ad.TK was injected intratumorally and patients received up to three doses at 30-day intervals. Positron emission tomography was used to monitor TK gene expression. Ad.TK injection was feasible in 100% of cases. Treatment was well tolerated and dose-limiting toxicity was not achieved. Cumulative toxicity was not observed. Hepatic toxicity was absent even in cirrhotic patients. Fever, flu-like syndrome, pain at the injection site and pancytopenia were the most common side effects. No partial responses were observed and 60% of patients showed tumor stabilization of the injected lesion. Importantly, two patients who received the highest dose showed signs of intratumoral necrosis by imaging procedures. One of them achieved a sustained stabilization and survived for 26 months. In conclusion, Ad.TK can be safely administered by intratumoral injection to patients with HCC up to 2 × 10¹² vp per patient.

Hallazgos neurorradiológicos de la Acidosis Glutárica tipo I / No disponible

La acidosis glutárica tipo I (AGTI) es un trastorno poco frecuente del metabolismo de los ácidos orgánicos consecuencia de un défi cit congénito de la enzima mitocondrial glutaril-CoA deshidrogenasa. Existe una alteración del metabolismo de los aminoácidos triptófano, lisina e hidroxilisina y se produce un aumento de los niveles de ácido glutárico que clínicamente se manifi esta con crisis distónicas agudas en niños de corta edad. La acumulación de ácido glutárico produce neurotoxicidad en los ganglios de la base y corteza fronto-temporal lo que puede causar distonía progresiva, hipotonía, disartria y crisis epilépticas. El diagnóstico precoz de esta enfermedad es crucial ya que la dieta y el tratamiento pueden alterar su historia natural. Presentamos los hallazgos neuroradiológicos de una adolescente de 16 años con AGTI que presentaba un síndrome distónico crónico. La RM demostró afectación del putamen de forma bilateral y de la sustancia blanca periventricular, además de atrofi a temporal en ambos hemisferios y ensanchamiento de ambas cisuras de Silvio

Glutaric aciduria type I is a rare disorder of organic acid metabolism caused by defi ciency of glutaryl-CoA dehydrogenase, a mitochondrial enzyme. Improper degeneration of amino acids: tryptophan, lysine, and hydroxylysine, results in increased levels of glutaric acid, which typically becomes clinically manifest as an acute dystonic crisis in young children. Accumulation of glutaric acid causes neurotoxicity in the basal ganglia and fronto-temporal cortex which can lead to progressive dystonia, hypotonia, permanently impaired speech and seizures. Because dietary and drug therapy may alter the natural history of the disease, early diagnosis of such patients is critical. We report the magnetic resonance (MR) imaging fi ndings in a 16 year-old girl with this disorder who presented with a chronic dystonic syndrome and previously diagnosed of brain paralysis. MR imaging demonstrated bilateral involvement of the putamina and periventricular white matter, and bilateral temporal atrophy and widened Silvian fi ssures

[Neuroradiologic findings of glutaric aciduria type I]. / Hallazgos neurorradiológicos de la Acidosis Glutárica tipo I.

Glutaric aciduria type I is a rare disorder of organic acid metabolism caused by deficiency of glutaryl-CoA dehydrogenase, a mitochondrial enzyme. Improper degeneration of amino acids: tryptophan, lysine, and hydroxylysine, results in increased levels of glutaric acid, which typically becomes clinically manifest as an acute dystonic crisis in young children. Accumulation of glutaric acid causes neurotoxicity in the basal ganglia and fronto-temporal cortex which can lead to progressive dystonia, hypotonia, permanently impaired speech and seizures. Because dietary and drug therapy may alter the natural history of the disease, early diagnosis of such patients is critical. We report the magnetic resonance (MR) imaging findings in a 16 year-old girl with this disorder who presented with a chronic dystonic syndrome and previously diagnosed of brain paralysis. MR imaging demonstrated bilateral involvement of the putamina and periventricular white matter, and bilateral temporal atrophy and widened Silvian fissures.

Doppler ultrasound for TIPS: does it work?

The role of transjugular intrahepatic portosystemic shunt (TIPS) in the management of complications of portal hypertension such as variceal hemorrhage and ascites is well established. However, TIPS has a limited patency due to dysfunction consisting in occlusion or stenosis of the intrahepatic tract or stenosis of the outflow hepatic vein. Timing of dysfunction cannot be predicted, so routine surveillance and percutaneous intervention are continuously required to maintain TIPS patency. Trans-shunt venography is the gold standard technique in TIPS evaluation, but it is expensive and invasive. Doppler ultrasound (DU) has been the most commonly used noninvasive tool in TIPS patency. Despite many reported series, its role remains controversial. After more than 10 years of experience with TIPS, we followed our patients with DU and trans-shunt venography to establish Doppler criteria of dysfunction and its accuracy in assessing shunt dysfunction.

Linfangioma de pared torácica. A propósito de un caso / No disponible

El linfangioma es una malformación congénita derivada de los vasos linfáticos y localizada generalmente en la cabeza o en el cuello. La ecografía es útil para orientar el diagnóstico. El tratamiento de elección es la cirugía, siempre que no sea mutilante. Existen otras alternativas terapéuticas como la inyección intralesional de agentes esclerosantes como el OK-432 que es seguro y muchas veces eficaz. Presentamos el caso de un linfangioma de pared torácica en un niño cuya resolución aconteció después de la punción-aspiración realizada al diagnóstico (AU)

Lymphangioma is a benign, congenital type of tumor, derived from lymphatic vessels, and located generally in head and neck. Ultrasonography is the procedure of choice for establishing the diagnosis. The main treatment modality is surgical excision, if it is not mutilating. Intralesional injection OK-432 represents an alternative, safe and effective treatment for lymphangiomas. We present a case of lymphangioma on the thoracic wall, solved after the punction (AU)