ABSTRACT
La Sección de Vía Aérea de la Sociedad Catalana de Anestesiología, Reanimación y Terapéutica del Dolor (SCARTD) presenta la actualización de las recomendaciones para la evaluación y manejo de la vía aérea difícil con el fin de incorporar los avances técnicos y los cambios observados en la práctica clínica desde la publicación de la primera edición en 2008. La metodología elegida fue la adaptación de 5 guías internacionales recientemente publicadas, cuyo contenido fue previamente analizado y comparado de forma estructurada, y el consenso de expertos de los 19 centros participantes. El documento final fue sometido a la valoración de los miembros de la SCARTD y a la revisión por parte de 11 expertos independientes. Estas recomendaciones están pues sustentadas en la evidencia científica actualmente disponible y en un amplio acuerdo de los profesionales de su ámbito de aplicación. En esta edición se amplía la definición de vía aérea difícil, abarcando todas las técnicas de manejo, y se hace mayor hincapié en la valoración de la vía aérea y en la clasificación en 3 categorías según el potencial grado de dificultad y las consideraciones de seguridad adicionales, que guiarán la planificación de la estrategia a seguir. La preparación previa al manejo de la vía aérea, no solo relativa al paciente y al material, sino también a la comunicación e interacción entre todos los agentes implicados, ocupa un lugar destacado en todos los escenarios incluidos en el presente documento. El texto refleja el aumento progresivo del uso de los videolaringoscopios y de los dispositivos de segunda generación en nuestro entorno y promueve tanto su uso electivo como el uso precoz en la vía aérea no prevista. También recoge la creciente utilización de la ecografía como herramienta de apoyo en la exploración y toma de decisiones. Se han abordado nuevos escenarios como el riesgo de broncoaspiración y la extubación considerada difícil. Finalmente, se trazan las líneas maestras de los programas de entrenamiento y formación continuada en vía aérea necesarios para garantizar la implementación efectiva y segura de las recomendaciones
The Airway Division of the Catalan Society of Anaesthesiology, Intensive Care and Pain Management (SCARTD) presents its latest guidelines for the evaluation and management of the difficult airway. This update includes the technical advances and changes observed in clinical practice since publication of the first edition of the guidelines in 2008. The recommendations were defined by a consensus of experts from the 19 participating hospitals, and were adapted from 5 recently published international guidelines following an in-depth analysis and systematic comparison of their recommendations. The final document was sent to the members of SCARTD for evaluation, and was reviewed by 11 independent experts. The recommendations, therefore, are supported by the latest scientific evidence and endorsed by professionals in the field. This edition develops the definition of the difficult airway, including all airway management techniques, and places emphasis on evaluating and classifying the airway into 3 categories according to the anticipated degree of difficulty and additional safety considerations in order to plan the management strategy. Pre-management planning, in terms of preparing patients and resources and optimising communication and interaction between all professionals involved, plays a pivotal role in all the scenarios addressed. The guidelines reflect the increased presence of video laryngoscopes and second-generation devices in our setting, and promotes their routine use in intubation and their prompt use in cases of unanticipated difficult airway. They also address the increased use of ultrasound imaging as an aid to evaluation and decision-making. New scenarios have also been included, such as the risk of bronchoaspiration and difficult extubation Finally, the document outlines the training and continuing professional development programmes required to guarantee effective and safe implementation of the guidelines
Subject(s)
Humans , Airway Management/methods , Anesthesia, Endotracheal/methods , Anesthetics/administration & dosage , Intubation, Intratracheal/methods , Airway Extubation/methods , Consensus , Airway Obstruction/prevention & control , Preoperative Care/methodsABSTRACT
The Airway Division of the Catalan Society of Anaesthesiology, Intensive Care and Pain Management (SCARTD) presents its latest guidelines for the evaluation and management of the difficult airway. This update includes the technical advances and changes observed in clinical practice since publication of the first edition of the guidelines in 2008. The recommendations were defined by a consensus of experts from the 19 participating hospitals, and were adapted from 5 recently published international guidelines following an in-depth analysis and systematic comparison of their recommendations. The final document was sent to the members of SCARTD for evaluation, and was reviewed by 11 independent experts. The recommendations, therefore, are supported by the latest scientific evidence and endorsed by professionals in the field. This edition develops the definition of the difficult airway, including all airway management techniques, and places emphasis on evaluating and classifying the airway into 3 categories according to the anticipated degree of difficulty and additional safety considerations in order to plan the management strategy. Pre-management planning, in terms of preparing patients and resources and optimising communication and interaction between all professionals involved, plays a pivotal role in all the scenarios addressed. The guidelines reflect the increased presence of video laryngoscopes and second-generation devices in our setting, and promotes their routine use in intubation and their prompt use in cases of unanticipated difficult airway. They also address the increased use of ultrasound imaging as an aid to evaluation and decision-making. New scenarios have also been included, such as the risk of bronchoaspiration and difficult extubation Finally, the document outlines the training and continuing professional development programmes required to guarantee effective and safe implementation of the guidelines.
Subject(s)
Airway Management/standards , Airway Management/methods , Anesthesia , Critical Care , Decision Trees , Humans , Pain ManagementABSTRACT
Kidney involvement associated to lymphoma is a known phenomenon but frequently not characterized due to the low frequency with which biopsies are realized in these patients. Several histological patterns can co-exist and happen unnoticed without a biopsy. Parenchyma infiltration in kidney for lymphoma has been found in 34% (post-mortem) and 14% (pre-mortem) and have low incident of clinical manifestations. Other patterns of renal injury are associated to lymphoma and minimal changes disease is especially related with Hodgkin's lymphoma. Renal lesions associated to paraprotein in lymphoplasmacytic lymphoma are an exceptional association, in spite of in 20% of them, appear cryoglobulinemia. There are a few cases reported in the literature with different histological patterns: light-chain disease, amyloidosis, and immunotactoid glomerulopathy related with kidney injury in patients with lymphoma. A 39-year-old male presented an association among paraproteinemia, membrano-proliferative glomerulonephritis no hepatitis C virus related and lymphoplasmacytic lymphoma with renal infiltration. This case emphasized the variety of renal lesions that lymphomas could trigger and the value of the nephropathology in the diagnosis and outcome of the hematologic diseases with paraproteinemia.
Subject(s)
Cryoglobulinemia/etiology , Glomerulonephritis, Membranoproliferative/complications , Kidney/pathology , Waldenstrom Macroglobulinemia/complications , Adult , Antibodies, Monoclonal, Murine-Derived/therapeutic use , Biopsy , Disease Progression , Edema/etiology , Glomerulonephritis, Membranoproliferative/blood , Glomerulonephritis, Membranoproliferative/pathology , Hepatitis C , Humans , Male , Nephrotic Syndrome/etiology , Plasma Exchange , Proteinuria/etiology , Purpura/etiology , Rituximab , Vasculitis/etiology , Waldenstrom Macroglobulinemia/blood , Waldenstrom Macroglobulinemia/diagnosis , Waldenstrom Macroglobulinemia/drug therapy , Waldenstrom Macroglobulinemia/pathology , Waldenstrom Macroglobulinemia/therapyABSTRACT
La afectación renal asociada a linfoma es un fenómeno conocido pero frecuentemente no caracterizado debido a la baja frecuencia con que se realizan biopsias en estos pacientes. Varios patrones histológicos pueden coexistir y pasar desapercibidos sin un estudio histopatológico. La infiltración parenquimatosa renal por linfoma no es infrecuente, y se ha encontrado hasta en un 34% (post mortem) y 14% (pre mortem), aunque tiene una baja incidencia de manifestaciones clínicas. Existen diferentes patrones de lesión renal asociados a linfoma y destaca la asociación de enfermedad de cambios mínimos con linfoma de Hodgkin. La afectación renal asociada a paraproteínas sintetizadas por un linfoma linfoplasmocitario es una asociación excepcional pese a que existen un 20% de pacientes afectados por dichos linfomas que presentan crioglobulinemia. En la literatura se han publicado casos de enfermedad de cadenas ligeras, amiloidosis, glomerulonefritis inmunotactoide como causas de paraproteinemia, proteinuria e insuficiencia renal en pacientes con linfoma. Presentamos un caso de asociación entre paraproteinemia, glomerulonefritis membrano-proliferativa y la aparición clínicamente evidente de un linfoma linfoplasmocitario en ausencia de infección por virus de la hepatitis C. Esto demuestra la afectación polimorfa que pueden presentar los linfomas en el riñón y el valor de la nefropatología en el diagnóstico y pronóstico de las enfermedades hematológicas que cursan con paraproteinemia (AU)
Kidney involvement associated to lymphoma is a known phenomenon but frequently not characterized due to the low frequency with which biopsies are realized in these patients. Several histological patterns can co-exist and happen unnoticed without a biopsy. Parenchyma infiltration in kidney for lymphoma has been found in 34% (post-mortem) and 14% (pre-mortem) and have low incident of clinical manifestations. Other patterns of renal injury are associated to lymphomaand minimal changes disease is especially related with Hodgkin's lymphoma. Renal lesions associated to paraprotein in lymphoplasmocitic lymphoma are an exceptional association, in spite of in 20% of them, appear cryoglobulinemia. There are a few cases reported in the literature with different histological patterns: light-chain disease, amyloidosis, and immuotactoid glomerulopathy related with kidney injury in patients with lymphoma. A 39-year-old male presented an association among paraproteinemia, membrano-proliferative glomerulonephritis no hepatitis C virus related and lymphoplasmocitic lymphoma with renal infiltration. This case emphasized the variety of renal lesions that lymphomas could trigger and the value of the nephropatology in the diagnosis and outcome of the hematologic diseases with paraproteinemia (AU)
Subject(s)
Humans , Male , Adult , Cryoglobulinemia/physiopathology , Waldenstrom Macroglobulinemia/physiopathology , Glomerulonephritis, Membranoproliferative/pathology , Biopsy , Nephritis/physiopathologyABSTRACT
INTRODUCTION: The aim of this study was to evaluate the experience of a renal transplantation unit in the management of human immunodeficiency virus (HIV)-infected patients with end-stage renal disease (ESRD). METHODS: A prospective study was performed between 2005 and 2010 among 23 patients with ESRD. RESULTS: In this study 83% of HIV-infected patients with ESRD were included on the waiting list for renal transplantation with 4 patients in a clinical evaluation phase. During the follow-up, 52% of waiting list patients (n = 11) received a renal transplant, and 1 patient underwent a simultaneous kidney-pancreas transplantation. Among the waiting list group we observed a significant later exclusion (43%; n = 3). Among the transplanted group there was a high but clinically inconsequential prevalence of acute tubular necrosis (36%; n = 4) and acute rejection episodes (36%; n = 4). The renal function showed a serum creatinine of 1.1 mg/dL at a follow-up of 24 + 12 months. All patients on the waiting list and after the transplantation are prescribed combined antiretroviral treatment (cART) with a low viral load <50 with CD4 >200. CONCLUSIONS: HIV-infected patients with ESRD should be considered to be candidates for renal transplantation if they meet the HIV inclusion criteria. Renal transplantation in adequately selected HIV-infected patients is a safe procedure with acceptable patient and graft survivals.
Subject(s)
HIV Infections/complications , Kidney Failure, Chronic/surgery , Kidney Transplantation , Waiting Lists , Adult , Anti-HIV Agents/therapeutic use , Biomarkers/blood , Creatinine/blood , Female , Graft Rejection/blood , Graft Rejection/immunology , Graft Survival , HIV Infections/diagnosis , HIV Infections/drug therapy , HIV Infections/mortality , Humans , Kidney Failure, Chronic/complications , Kidney Transplantation/adverse effects , Kidney Transplantation/immunology , Kidney Transplantation/mortality , Kidney Tubular Necrosis, Acute/etiology , Male , Middle Aged , Patient Selection , Prospective Studies , Spain , Survival Analysis , Survival Rate , Time Factors , Treatment Outcome , Waiting Lists/mortalityABSTRACT
No disponible
Subject(s)
Humans , Oxalates/adverse effects , Acute Kidney Injury/etiology , Hyperoxaluria/complications , Risk Factors , Malabsorption Syndromes/complicationsSubject(s)
Acute Kidney Injury/etiology , Calcium Oxalate/metabolism , Hyperoxaluria/etiology , Short Bowel Syndrome/complications , Aged , Bile Duct Neoplasms/surgery , Bile Ducts, Intrahepatic , Biliary Fistula/etiology , Calcium Oxalate/pharmacokinetics , Cardiac Output, High/etiology , Cholangiocarcinoma/surgery , Crystallization , Dietary Fats/pharmacokinetics , Drainage/adverse effects , Humans , Intestinal Absorption , Ischemia/etiology , Liver/blood supply , Male , Postoperative Complications , Proteinuria/etiology , Short Bowel Syndrome/metabolism , Surgical Wound Infection/etiology , Surgical Wound Infection/surgeryABSTRACT
Post-dilution on-line hemodiafiltration (OL-HDF) is the most efficient infusion mode to obtain maximum clearances of uremic toxins, with a recommended manual infusion flow (Qi) of 25% of the blood flow with the main limitation that causes alarms by hemoconcentration throughout the session. Recent technical advances allow automatic prescription of Qi if hematocrit and total protein (TP) values are specified. As these analytical results are not possible to obtain in each dialysis session, a practical way to prescribe Qi is to make an automatic prescription adjusting the hematocrit and total protein values at the beginning of the session to obtain the manual prescription required and we will call it automatic-manual prescription. The aim of this study was to compare manual Qi with automatic-manual Qi in postdilution OL-HDF. 30 patients (16 men and 14 women), 59.9 +/- 15 years old, in hemodialysis program for 50.1 +/- 67 months were included. Every patient underwent four OL-HDF sessions, two with manual Qi (4008-S and 5008 monitors) and two with automatic-manual Qi (A-M), one with the same Qi and one with manual Qi +20 (A-M+20). The same usual dialysis parameters were maintained: helixone dialyzer, dialysis time of 266 +/- 39 minutes, blood flow of 420 +/- 36. Recirculation, Kt and intradialysis alarms were measured at each session. No significant differences in the fistula recirculation or dialysis dose measured using Kt. Total infusion volume was 24.9 +/- 4 (4008 S), 23.4 +/- 4 L (5008) with manual Qi, 23.6 +/- 4 L (A-M) Qi (NS) and 25.8 +/- 5 L (A-M+20). Only 14% of patients had no incidents. The number of alarms was significantly higher with manual prescription 55 alarms with 4008 and 40 with 5008 vs. AM (11) p < 0.01) and A-M+20 (16 alarms) We concluded that automatic-manual Qi is a practical way for post-dilutional OL-HDF prescription where the same efficiency and total reinfusion volume with an important reduction of intradialysis alarms are obtained, allowing to rise Qi by 20% without increasing intradialysis alarms.
Subject(s)
Hemodiafiltration/methods , Kidney Failure, Chronic/therapy , Prescriptions , Adult , Aged , Algorithms , Automation , Blood Proteins/analysis , Clinical Alarms , Female , Hematocrit , Hemodiafiltration/instrumentation , Humans , Male , Middle Aged , Online Systems , Pressure , Rheology , Urea/analysisABSTRACT
La hemodiafiltración on-line (HDF-OL) posdilucional es la modalidad más eficaz para obtener la máxima depuración de toxinas urémicas, con un flujo de infusión (Qi) recomendable del 25% del flujo sanguíneo y con el principal inconveniente de provocar alarmas por hemoconcentración a lo largo de la sesión. Recientes avances técnicos permiten la prescripción automática del Qi si se especifican los valores del hematocrito y de las proteínas totales. Como no es posible disponer en cada sesión de estos valores, una forma práctica de pautar la HDF-OL posdilucional es realizar una prescripción automática ajustando el hematocrito y las proteínas totales para obtener al inicio de la sesión la prescripción manual prescrita, a la que llamaremos prescripción manual automatizada. El objetivo del estudio fue comparar la pauta convencional de Qi manual respecto a la manual automatizada. Se incluyeron 30 pacientes (16 varones y 14 mujeres), de 59,9 ± 15 años de edad, en programa de hemodiálisis durante 50,1 ± 67 meses. Cada paciente recibió cuatro sesiones de HDF-OL, dos con Qi manual (monitores 4008-S y 5008) y dos con Qi manual automatizada (M-A), una con Qi igual a la manual y otra incrementando el Qi 20 ml/min (M-A+20). El resto de parámetros de diálisis no variaron: filtro de helixona, tiempo de diálisis 266 ± 39 minutos, flujo de sangre 420 ± 36 ml/min. En cada sesión se recogieron el Kt, la recirculación y las alarmas. No se observaron diferencias significativas en el índice de recirculación ni en la dosis de diálisis medida con el Kt. El volumen total de infusión fue de 24,9 ± 4 l (4008S), 23,4 ± 4 l (5008) con Qi manual, 23,6 ± 4 l (M-A) y 25,8 ± 5 l (M-A+20). En sólo el 14% de los pacientes no hubo incidencias. El número de alarmas fue significativamente superior con la prescripción manual, 55 alarmas con 4008 y 40 con 5008, respecto a la M-A (11, p <0,01) y M-A+20 (16 alarmas). Concluimos que la prescripción del Qi manual automatizada es una forma práctica de prescribir la HDF-OL posdilucional consiguiendo el mismo volumen convectivo y la misma eficacia, con una importante reducción de las alarmas intradiálisis, lo que permite un incremento del Qi un 20% sin aumento del número de alarmas (AU)
Post-dilution on-line hemodiafiltration (OL-HDF) is the most efficient infusion mode to obtain maximum clearances of uremic toxins, with a recommended manual infusion flow (Qi) of 25% of the blood flow with the main limitation that causes alarms by hemoconcentration throughout the session. Recent technical advances allow automatic prescription of Qi if hematocrit and total protein (TP) values are specified. As these analytical results are not possible to obtain in each dialysis session, a practical way to prescribe Qi is to make an automatic prescription adjusting the hematocrit and total protein values at the beginning of the session to obtain the manual prescription required and we will call it automatic-manual prescription. The aim of this study was to compare manual Qi with automatic- manual Qi in postdilution OL-HDF. 30 patients (16 men and 14 women), 59.9 ± 15 years old, in hemodialysis program for 50.1 ± 67 months were included. Every patient underwent four OL-HDF sessions, two with manual Qi (4008-S and 5008 monitors) and two with automatic- manual Qi (A-M), one with the same Qi and one with manual Qi +20 (A-M+20). The same usual dialysis parameters were maintained: helixone dialyzer, dialysis time of 266 ± 39 minutes, blood flow of 420 ± 36. Recirculation, Kt and intradialysis alarms were measured at each session. No significant differences in the fistula recirculation or dialysis dose measured using Kt. Total infusion volume was 24.9 ± 4 (4008S), 23.4 ± 4 L (5008) with manual Qi, 23.6 ± 4 L (A-M) Qi (NS) and 25.8 ± 5 L (A-M+20). Only 14% of patients had no incidents. The number of alarms was significantly higher with manual prescription 55 alarms with 4008 and 40 with 5008 vs. AM (11) p <0.01) and A-M+20 (16 alarms) We concluded that automatic-manual Qi is a practical way for post-dilutional OL-HDF prescription where the same efficiency and total reinfusion volume with an important reduction of intradialysis alarms are obtained, allowing to rise Qi by 20% without increasing intradialysis alarms (AU)
Subject(s)
Humans , Hemodiafiltration/methods , Dialysis Solutions/pharmacology , Electronic Prescribing , Dosage/methods , Renal Dialysis/methods , Renal Insufficiency, Chronic/therapyABSTRACT
No disponible
Subject(s)
Humans , Male , Female , Predictive Value of Tests , Sensitivity and Specificity , Intubation/trends , Intubation , Intubation, Intratracheal/standards , Intubation, Intratracheal/trends , Anesthesia, Local/instrumentation , Anesthesia, Local/methods , Tracheotomy , Algorithms , Hypoxia/complications , Laryngoscopy/standards , LaryngoscopySubject(s)
Airway Obstruction/prevention & control , Anesthesiology/trends , Intraoperative Complications/prevention & control , Respiration, Artificial/methods , Aged , Airway Obstruction/epidemiology , Anesthesiology/methods , Contraindications , Equipment Design , Female , Fiber Optic Technology , Humans , Intubation, Intratracheal/instrumentation , Intubation, Intratracheal/methods , Laryngeal Masks , Laryngoscopy , Male , Middle Aged , Respiration, Artificial/instrumentation , Risk Factors , Societies, Medical , Video RecordingABSTRACT
No disponible
No disponible
Subject(s)
Humans , Anesthesia, Endotracheal/trends , Intubation, Intratracheal/methods , Airway Obstruction/complications , Anesthesiology/educationABSTRACT
Renal tumors can be associated with a thrombus that affects the renal vein and even the inferior vena cava. Radical surgery may require a 2-phase approach involving different anesthetic techniques: an abdominal approach for removal of the kidney and a thoracic approach for extraction of the thrombus, with extracorporeal circulation and in some cases cessation of blood circulation. We present 2 cases in which nephrectomy and thrombectomy were carried out with the support of extracorporeal circulation. The thrombus was in the renal vein and the inferior vena cava, extending to the outlet to the right atrium in both cases. In 1 case a portion reached the bifurcation of the pulmonary artery. The operation was performed under hypothermia to reduce circulation and did not require aortic clamping, cardioplegia, or cessation of blood flow.
Subject(s)
Anesthesia, Inhalation/methods , Carcinoma, Renal Cell/surgery , Hypothermia, Induced , Kidney Neoplasms/surgery , Nephrectomy/methods , Renal Veins/surgery , Thrombectomy/methods , Thrombosis/surgery , Vena Cava, Inferior/surgery , Wilms Tumor/surgery , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Blood Loss, Surgical , Carcinoma, Renal Cell/pathology , Combined Modality Therapy , Dactinomycin/administration & dosage , Doxorubicin/administration & dosage , Extracorporeal Circulation , Fatal Outcome , Female , Hemostatic Techniques , Humans , Kidney Neoplasms/drug therapy , Kidney Neoplasms/pathology , Male , Middle Aged , Multiple Organ Failure/etiology , Neoplasm Invasiveness , Postoperative Hemorrhage/drug therapy , Pulmonary Embolism/etiology , Renal Veins/pathology , Thrombosis/etiology , Vena Cava, Inferior/pathology , Vincristine/administration & dosage , Wilms Tumor/drug therapy , Wilms Tumor/pathologyABSTRACT
Los tumores renales pueden asociarse a un tromboque afecte a la vena renal e incluso a la vena cava inferior.La cirugía radical puede requerir de una intervenciónen dos tiempos con necesidades anestésicas diferentes:un abordaje abdominal para la resección del riñón yotro torácico para la extracción del trombo con circulaciónextracorpórea y en algunos casos de parada circulatoria.Presentamos dos casos en que se realizó nefrectomía ytrombectomía con soporte de circulación extracorpórea.El trombo se encontraba en la vena renal y vena cavainferior hasta la entrada de la aurícula derecha enambos casos y en uno de ellos un fragmento se desprendióhasta la bifurcación de la arteria pulmonar. La intervenciónse realizó con hipotermia para disminuir los flujoscirculatorios y no requirió de pinzamiento aórtico,cardioplejia, ni parada circulatoria
Renal tumors can be associated with a thrombus thataffects the renal vein and even the inferior vena cava.Radical surgery may require a 2-phase approach involvingdifferent anesthetic techniques: an abdominal approachfor removal of the kidney and a thoracic approachfor extraction of the thrombus, with extracorporeal circulationand in some cases cessation of blood circulation.We present 2 cases in which nephrectomy and thrombectomywere carried out with the support of extracorporealcirculation. The thrombus was in the renal veinand the inferior vena cava, extending to the outlet to theright atrium in both cases. In 1 case a portion reachedthe bifurcation of the pulmonary artery. The operationwas performed under hypothermia to reduce circulationand did not require aortic clamping, cardioplegia, orcessation of blood flow
Subject(s)
Male , Female , Adult , Middle Aged , Humans , Anesthesia, Inhalation/methods , Carcinoma, Renal Cell/surgery , Hypothermia, Induced , Nephrectomy/methods , Renal Veins/surgery , Thrombectomy/methods , Thrombosis/surgery , Vena Cava, Inferior/surgery , Kidney Neoplasms/surgery , Wilms Tumor/surgery , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Blood Loss, Surgical , Carcinoma, Renal Cell/pathology , Combined Modality Therapy , Dactinomycin/administration & dosage , Doxorubicin/administration & dosage , Extracorporeal Circulation , Hemostatic Techniques , Multiple Organ Failure/etiology , Neoplasm Invasiveness , Postoperative Hemorrhage/drug therapy , Pulmonary Embolism/etiology , Renal Veins/pathology , Thrombosis/etiology , Vena Cava, Inferior/pathology , Vincristine/administration & dosage , Fatal Outcome , Kidney Neoplasms/drug therapy , Kidney Neoplasms/pathology , Wilms Tumor/drug therapy , Wilms Tumor/pathologyABSTRACT
The sprouting of new blood vessels, or angiogenesis, is necessary for any solid tumor to grow large enough to cause life-threatening disease. Vascular endothelial growth factor (VEGF) is one of the key promoters of tumor induced angiogenesis. VEGF receptors, the tyrosine kinases Flt-1 and KDR, are expressed on vascular endothelial cells and initiate angiogenesis upon activation by VEGF. 1-Anilino-(4-pyridylmethyl)-phthalazines, such as CGP 79787D (or PTK787 / ZK222584), reversibly inhibit Flt-1 and KDR with IC(50) values < 0.1 microM. CGP 79787D also blocks the VEGF-induced receptor autophosphorylation in CHO cells ectopically expressing the KDR receptor (ED(50) = 34 nM). Modification of the 1-anilino moiety afforded derivatives with higher selectivity for the VEGF receptor tyrosine kinases Flt-1 and KDR compared to the related receptor tyrosine kinases PDGF-R and c-Kit. Since these 1-anilino-(4-pyridylmethyl)phthalazines are orally well absorbed, these compounds qualify for further profiling and as candidates for clinical evaluation.