ABSTRACT
We describe the case of an 82-year-old man who had recently undergone cardiac surgery (quadruple coronary bypass), who consulted due to the appearance of a necrotic eschar on the thumb of the right index finger, together with paraesthesia and hypoaesthesia in the first 3 fingers of the same hand. An ultrasound scan of the right elbow was performed to rule out involvement of the median nerve and an anechoic, thick-walled mass was found, dependent on the wall of the proximal ulnar artery, compatible with a pseudoaneurysm of the same, compressing the nerve. Electromyography showed an acute lesion of the proximal median nerve and angio-CT confirmed the diagnosis of pseudoaneurysm of the proximal ulnar artery. Pseudoaneurysm is a dilatation by rupture of the arterial wall, which does not involve all three layers of the arterial wall and communicates with the vascular lumen. Its development after vascular manipulation is very rare, and it is uncommon for it to act by compressing a nerve structure. In our case, together with vascular surgery, treatment with intralesional thrombin was decided, with good evolution.
Se describe el caso de un varón de 82 arios intervenido recientemente de cirugía cardíaca (cuádruple bypass coronario), que consulta por aparición de una escara necrótica en el pulpejo del dedo índice derecho, junto a parestesias e hipoestesias en los tres primeros dedos de dicha mano. Se realiza una ecografía del codo derecho para descartar afectación del nervio mediano y se objetiva una masa anecoica, de paredes engrosadas, dependientes de la pared de la arteria cubital proximal, compatible con pseudoaneurisma de esta, que comprime dicho nervio. En la electromiografía se evidencia una lesión aguda del nervio mediano a nivel proximal y en el angio-TC se confirma el diagnóstico de pseudoaneurisma de la arteria cubital proximal. El pseudoaneurisma es una dilatación por rotura de la pared arterial, que no implica a las tres capas de esta y se comunica con la luz vascular. Su desarrollo tras una manipulación vascular es muy infrecuente y que actúe comprimiendo una estructura nerviosa es poco común. En nuestro caso, conjuntamente con cirugía vascular se decidió tratamiento con trombina intralesional, con buena evolución.
Subject(s)
Humans , Male , Aged, 80 and over , Cardiovascular System , Arteries , Vascular Diseases , Blood Vessels , Cardiovascular Diseases , Ulnar Artery , Aneurysm, False , Peripheral Nervous System , Median Nerve , Nervous SystemABSTRACT
Vascular malformations (VM) are congenital, benign, and relatively frequent lesions. Scant data have been published about the epidemiology, clinical presentation, and treatment of VM from a dermatologist's perspective. The substantial differences between subtypes, broad range of specialists consulted and confusing nomenclature used over previous years may hamper a correct diagnosis. The main objective of this study is to describe VM epidemiology. As a secondary endpoint we evaluate clinical characteristics, clinical-radiological correlation and treatment approaches. We carried out an observational, descriptive, retrospective study. Cases presented to the multidisciplinary committee of our hospital from 2009 to 2019 were retrieved. Electronic medical records, monthly committee reports and the iconographic archive were reviewed and statistically analyzed. Overall, venous malformations (VeM) are the most frequent VM, followed by capillary malformations (CM), arterioVeM and lymphatic malformations (LM). Considering only patients under 16, CMs are the most frequent ones. Capillary and LMs are larger than venous or arteriovenous. While CMs are usually asymptomatic, symptomatic cases are threefold more frequent in the other subtypes. Decisions on active or conservative management depend on VM size but not location or patient age. CMs are mainly treated with laser therapy; venous with sclerotherapy or surgery; arteriovenous with surgery and lymphatic with surgery or sirolimus. Dermatologists play an important role in VM diagnosis and management. Our 10-year multidisciplinary experience should contribute to the literature and represent a practical resource for clinicians and researchers.
Subject(s)
Lymphatic Abnormalities , Vascular Malformations , Humans , Retrospective Studies , Sclerotherapy/adverse effects , Vascular Malformations/diagnosis , Vascular Malformations/epidemiology , Vascular Malformations/therapy , VeinsABSTRACT
Activation of AKT signaling by PTEN loss or PIK3CA mutations occurs frequently in human cancers, but targeting AKT has been difficult due to the mechanism-based toxicities of inhibitors that target the inactive conformation of AKT. Ipatasertib (GDC-0068) is a novel selective ATP-competitive small-molecule inhibitor of AKT that preferentially targets active phosphorylated AKT (pAKT) and is potent in cell lines with evidence of AKT activation. In this phase I study, ipatasertib was well tolerated; most adverse events were gastrointestinal and grade 1-2 in severity. The exposures of ipatasertib ≥200 mg daily in patients correlated with preclinical TGI90, and pharmacodynamic studies confirmed that multiple targets (i.e., PRAS40, GSK3ß, and mTOR) were inhibited in paired on-treatment biopsies. Preliminary antitumor activity was observed; 16 of 52 patients (30%), with diverse solid tumors and who progressed on prior therapies, had radiographic stable disease, and many of their tumors had activation of AKT. SIGNIFICANCE: Potent inhibition of AKT signaling with ipatasertib was associated with a tolerable safety profile and meaningful disease control in a subgroup of patients. Targeting pAKT with an ATP-competitive inhibitor provides a greater therapeutic window than allosteric inhibitors. Further investigation with ipatasertib is ongoing in phase II studies. Cancer Discov; 7(1); 102-13. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 1.
Subject(s)
Neoplasms/drug therapy , Piperazines/administration & dosage , Protein Kinase Inhibitors/administration & dosage , Pyrimidines/administration & dosage , Administration, Oral , Adult , Aged , Cell Line, Tumor , Drug Administration Schedule , Female , Humans , Male , Middle Aged , Neoplasms/genetics , Piperazines/adverse effects , Piperazines/pharmacology , Protein Kinase Inhibitors/adverse effects , Protein Kinase Inhibitors/pharmacology , Proto-Oncogene Proteins c-akt/antagonists & inhibitors , Pyrimidines/adverse effects , Pyrimidines/pharmacology , Xenograft Model Antitumor AssaysABSTRACT
No disponible
Subject(s)
Humans , Female , Middle Aged , Hyperplasia/complications , Hyperplasia , Soft Tissue Neoplasms , Immunohistochemistry/methods , Antigens, CD34/analysis , Endothelium, Vascular/pathology , Endothelium, Vascular , Magnetic Resonance Spectroscopy/methods , Ultrasonography/methods , Aneurysm, False/complications , Endothelium/pathology , EndotheliumABSTRACT
No disponible
Subject(s)
Humans , Male , Middle Aged , Pneumonectomy/adverse effects , Hernia/etiology , Heart Injuries/etiology , Pleural Neoplasms/complications , Torsion, Mechanical , Diagnostic ImagingABSTRACT
PURPOSE: Aurora A kinase (AAK) is a key regulator of mitosis and a target for anticancer drug development. This phase I study investigated the safety, pharmacokinetics, and pharmacodynamics of MLN8237 (alisertib), an investigational, oral, selective AAK inhibitor, in 59 adults with advanced solid tumors. EXPERIMENTAL DESIGN: Patients received MLN8237 once daily or twice daily for 7, 14, or 21 consecutive days, followed by 14 days recovery, in 21-, 28-, or 35-day cycles. Dose-limiting toxicities (DLT) and the maximum-tolerated dose (MTD) for the 7- and 21-day schedules were determined. Pharmacokinetic parameters were derived from plasma concentration-time profiles. AAK inhibition in skin and tumor biopsies was evaluated and antitumor activity assessed. RESULTS: Neutropenia and stomatitis were the most common DLTs. The MTD for the 7- and 21-day schedules was 50 mg twice daily and 50 mg once daily, respectively. MLN8237 absorption was fast (median time to maximum concentration, 2 hours). Mean terminal half-life was approximately 19 hours. At steady state, pharmacodynamic effects were shown by accumulation of mitotic and apoptotic cells in skin, and exposure-related increases in numbers of mitotic cells with characteristic spindle and chromosomal abnormalities in tumor specimens, supporting AAK inhibition by MLN8237. Stable disease was observed and was durable with repeat treatment cycles, administered over 6 months, in 6 patients, without notable cumulative toxicity. CONCLUSIONS: The recommended phase II dose of MLN8237 is 50 mg twice daily on the 7-day schedule, which is being evaluated further in a variety of malignancies, including in a phase III trial in peripheral T-cell lymphoma.
Subject(s)
Antineoplastic Agents/administration & dosage , Azepines/administration & dosage , Neoplasms , Protein Serine-Threonine Kinases/antagonists & inhibitors , Pyrimidines/administration & dosage , Adult , Aged , Antineoplastic Agents/adverse effects , Antineoplastic Agents/pharmacokinetics , Aurora Kinases , Azepines/adverse effects , Azepines/pharmacokinetics , Biopsy , Female , Humans , Male , Maximum Tolerated Dose , Middle Aged , Neoplasm Staging , Neoplasms/drug therapy , Neoplasms/pathology , Neutropenia/chemically induced , Protein Serine-Threonine Kinases/metabolism , Pyrimidines/adverse effects , Pyrimidines/pharmacokinetics , Stomatitis/chemically inducedABSTRACT
Las fístulas aortoentéricas son una entidad clínica infrecuente. Se clasifican en dos tipos: primarias y secundarias. Las primarias, más raras, consisten en una comunicación espontánea de la luz del aneurisma y el tubo digestivo, frecuentemente el duodeno. Las secundarias, más frecuentes, se presentan en pacientes con aneurismas que han sido tratados. El signo clínico de presentación más habitual de las fístulas aortoentéricas es la hemorragia digestiva alta. La sospecha clínica de esta entidad es fundamental para su diagnóstico. La endoscopía y la tomografía computarizada son las técnicas complementarias más usadas para el diagnóstico, aunque en la mayoría de las ocasiones son negativas y el diagnóstico se realiza en la cirugía. El tratamiento de elección es la cirugía, si bien existen casos descritos tratados mediante técnicas endovasculares. Presentamos dos casos de fístulas aortoentéricas primarias y revisamos la literatura publicada al respecto.
