RESUMEN
PURPOSE: In mCRC, disease dynamics may play a critical role in the understanding of long-term outcome. We evaluated depth of response (DpR), time to DpR, and post-DpR survival as relevant endpoints. METHODS: We analyzed DpR by central review of computer tomography images (change from baseline to smallest tumor diameter), early tumor shrinkage (≥ 20% reduction in tumor diameter at first reassessment), time to DpR (study randomization to DpR-image), post-DpR progression-free survival (pPFS = DpR-image to tumor progression or death), and post-DpR overall survival (pOS = DpR-image to death) with special focus on BRAF status in 66 patients and primary tumor site in 86 patients treated within the VOLFI-trial, respectively. RESULTS: BRAF wild-type (BRAF-WT) compared to BRAF mutant (BRAF-MT) patients had greater DpR (- 57.6% vs. - 40.8%, p = 0.013) with a comparable time to DpR [4.0 (95% CI 3.1-4.4) vs. 3.9 (95% CI 2.5-5.5) months; p = 0.8852]. pPFS was 6.5 (95% CI 4.9-8.0) versus 2.6 (95% CI 1.2-4.0) months in favor of BRAF-WT patients (HR 0.24 (95% CI 0.11-0.53); p < 0.001). This transferred into a significant difference in pOS [33.6 (95% CI 26.0-41.3) vs. 5.4 (95% CI 5.0-5.9) months; HR 0.27 (95% CI 0.13-0.55); p < 0.001]. Similar observations were made for patients stratified for primary tumor site. CONCLUSIONS: BRAF-MT patients derive a less profound treatment response compared to BRAF-WT patients. The difference in outcome according to BRAF status is evident after achievement of DpR with BRAF-MT patients hardly deriving any further disease control beyond DpR. Our observations hint towards an aggressive tumor evolution in BRAF-MT tumors, which may already be molecularly detectable at the time of DpR.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Mutación , Proteínas Proto-Oncogénicas B-raf/genética , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Camptotecina/administración & dosificación , Camptotecina/análogos & derivados , Neoplasias Colorrectales/enzimología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Progresión de la Enfermedad , Femenino , Fluorouracilo/administración & dosificación , Humanos , Leucovorina/administración & dosificación , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Compuestos Organoplatinos/administración & dosificación , Panitumumab/administración & dosificación , Resultado del Tratamiento , Proteínas ras/genéticaRESUMEN
BACKGROUND: This prospective multicentre phase II trial assessed the feasibility and efficacy of perioperative chemotherapy with docetaxel, cisplatin and capecitabine (DCX) in patients with gastro-oesophageal adenocarcinoma. METHODS: Patients with curatively resectable adenocarcinoma of the stomach, the gastro-oesophageal junction or the lower third of the oesophagus were enrolled. Patients received docetaxel 75 mg/m(2) plus cisplatin 60 mg/m(2) (day 1), followed by oral capecitabine 1875 mg/m(2) divided into two doses (days 1-14) every 3 weeks. There were three cycles preoperatively and three cycles postoperatively. The primary end point was the R0 resection rate. RESULTS: Fifty-one patients were recruited and assessed for feasibility and efficacy. 94.1% of patients received all three planned cycles preoperatively, and 52.9% received three cycles postoperatively. The R0 resection rate was 90.2%. 13.7% of patients showed complete pathological remission (pCR). Toxicity was acceptably tolerable. Without prophylactic granulocyte colony-stimulating factor administration, neutropenic fever developed in 21.5% of patients preoperatively (grade 3 or 4) and in 11.1% of patients postoperatively. CONCLUSIONS: DCX is a safe and feasible perioperative regimen in the treatment of gastro-oesophageal adenocarcinoma with a high percentage of cycles delivered pre- and postoperatively, compared with standard practice. The high efficacy in terms of R0 resection rate and pCR is very promising.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Esofágicas/tratamiento farmacológico , Unión Esofagogástrica , Neoplasias Gástricas/tratamiento farmacológico , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Capecitabina , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Cisplatino/uso terapéutico , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapéutico , Docetaxel , Esquema de Medicación , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/cirugía , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Fluorouracilo/análogos & derivados , Fluorouracilo/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Taxoides/administración & dosificación , Taxoides/efectos adversos , Taxoides/uso terapéutico , Resultado del TratamientoRESUMEN
A peculiar clinical presentation of post-traumatic complex left foot fracture deformity is presented in this report as the result of a motorbike accident. Notwithstanding the significant deformity following forefoot fractures, the patient complained only of the recent onset of metatarsalgia. Of particular interest, is that this severe foot injury as well following deformity was overlooked, probably because patient had sustained head injury that was the main problem to treat due to life risk.
Asunto(s)
Deformidades del Pie/etiología , Traumatismos de los Pies/complicaciones , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Multiple myeloma is a low malignant, non-Hodgkin's lymphoma, which is characterised by infiltration of the bone marrow by clonal prolifaration of atypical plasma cells. Clinical presentation is mostly determined by the sequeles of displacement of normal hemopoiesis, destruction of bones and the immune deficiency. Extramedullary manifestations are relatively rare. Pulmonary and pleural involvement has been described in case reports only. We report on a 75-year-old male patient in whom an IgG-secreting multiple myeloma type lambda, stage III (according to Durie and Salmon) has been diagnosed. Chest X-ray and CT revealed a diffuse confluent nodular pattern in the lungs and a large left-sided pleural effusion. Histology and immunohistochemistry confirmed diffuse infiltration of the lungs as well as the pleura by dysmature plasma cells with deposition of lambda-light chains. Preliminary treatment with vincristine and prednisone followed by polychemotherapy according to the VAD scheme was performed, which led to resolution of the pleuropulmonary changes.
Asunto(s)
Neoplasias Pulmonares/diagnóstico , Mieloma Múltiple/diagnóstico , Neoplasias Pleurales/diagnóstico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Doxorrubicina/administración & dosificación , Etopósido/administración & dosificación , Humanos , Inmunoglobulina G/metabolismo , Cadenas lambda de Inmunoglobulina/metabolismo , Pulmón/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Masculino , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/patología , Células Plasmáticas/patología , Pleura/patología , Derrame Pleural Maligno/patología , Neoplasias Pleurales/tratamiento farmacológico , Neoplasias Pleurales/patología , Prednisona/administración & dosificación , Vincristina/administración & dosificaciónRESUMEN
Diffuse pulmonary hemorrhage denotes a diffuse bleeding into the alveoli as a result of severe damage of the alveolocapillary membrane. Autoimmune diseases, toxic injury and hemodynamic changes are the most frequent causes. A 45 year old male patient presented with diffuse alveolar hemorrhage. An Immunoglobulin A (IgA) paraprotein secreting myeloma was found to be the underlying cause. Immunohistochemistry revealed dense pericapillary and perivascular deposits of IgA, indicating a paraprotein mediated damage of the alveolocapillary membrane. The predominantly vascular pattern of damage was regarded as the most likely cause of the pulmonary hypertension in this patient. The diffuse pulmonary bleeding stopped after initiation of treatment consisting of vincristine, adriamycine and dexamethasone.
Asunto(s)
Hemorragia/etiología , Inmunoglobulina A/sangre , Cadenas kappa de Inmunoglobulina/sangre , Enfermedades Pulmonares/etiología , Neoplasias Pulmonares/diagnóstico , Paraproteinemias/diagnóstico , Plasmacitoma/diagnóstico , Nódulo Pulmonar Solitario/etiología , Electroforesis de las Proteínas Sanguíneas , Diagnóstico Diferencial , Electrocardiografía , Glomerulonefritis por IGA/sangre , Glomerulonefritis por IGA/complicaciones , Glomerulonefritis por IGA/diagnóstico , Glomerulonefritis por IGA/patología , Hemorragia/sangre , Hemorragia/patología , Humanos , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/patología , Inmunoelectroforesis , Glomérulos Renales/patología , Enfermedades Pulmonares/sangre , Enfermedades Pulmonares/patología , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Paraproteinemias/sangre , Paraproteinemias/complicaciones , Paraproteinemias/patología , Plasmacitoma/sangre , Plasmacitoma/complicaciones , Plasmacitoma/patología , Alveolos Pulmonares/patología , Tomografía Computarizada por Rayos XRESUMEN
In general, the mobilization of peripheral blood progenitor cells (PBPC) in multiple myeloma (MM) patients is poor and is achieved in most cases by combined cyclophosphamide and G-CSF. This study was performed to examine the efficacy of combined ifosfamide/epirubicine and G-CSF for PBPC mobilization and purging. Sixteen patients suffering from multiple myeloma in stage II/A and III/A according to Durie and Salmon underwent chemotherapy consisting of a total of three cycles of ifosfamide (3 g/m(2) on days 1 and 2 and epirubicine 80 mg/m(2) on day 1) and G-CSF (10 or 20 microg/kg body weight (BW) daily until harvesting). PBPC harvesting was performed after the first and third cycle of chemotherapy. The median number of PBPC after the first cycle of chemotherapy was 7.79 x 10(6) CD34+ cells/kg BW (ranging from 0.94-26.36 x 10(6)) and 6.38 x 10(6) CD34+ cells/kg BW (ranging from 0.79-29.31 x 10(6)) after the third cycle of chemotherapy. Clinical re-evaluation after three cycles of chemotherapy showed 13 (81 per cent) patients in partial remission (PR), two (12 per cent) in complete remission (CR) and one (6.25 per cent) in stable disease (SD). No major side-effects were observed, six patients developed hematological toxicity stage IV WHO for a median of 3.9 days but no serious infection episodes occurred. Combined ifosfamide/epirubicin and standard G-CSF is able to mobilize sufficient PBPC without serious side-effects for patients with MM and for purging procedures resulting in a high proportion of complete remissions after tandem high-dose melphalan chemotherapy.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Epirrubicina/administración & dosificación , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Movilización de Célula Madre Hematopoyética/métodos , Ifosfamida/administración & dosificación , Mieloma Múltiple/tratamiento farmacológico , Adulto , Antibióticos Antineoplásicos/administración & dosificación , Antibióticos Antineoplásicos/normas , Antibióticos Antineoplásicos/toxicidad , Antineoplásicos Alquilantes/administración & dosificación , Antineoplásicos Alquilantes/normas , Antineoplásicos Alquilantes/toxicidad , Purgación de la Médula Ósea/métodos , Purgación de la Médula Ósea/normas , Epirrubicina/normas , Epirrubicina/toxicidad , Femenino , Factor Estimulante de Colonias de Granulocitos/normas , Factor Estimulante de Colonias de Granulocitos/toxicidad , Movilización de Célula Madre Hematopoyética/efectos adversos , Humanos , Ifosfamida/normas , Ifosfamida/toxicidad , Leucopenia/inducido químicamente , Masculino , Persona de Mediana Edad , Mieloma Múltiple/complicaciones , Estudios Prospectivos , Equivalencia TerapéuticaRESUMEN
We report on a 49 year old female with primary extra-medullary manifestation of a acute myeloid leukemia in the lungs without leukemic signs. The disease was diagnosed by detection of leukemic blast cells in bronchoalveolar lavage. Chemotherapy with the TAD-VP-scheme resulted in partial remission. The patient died in systemic early relapse. To our knowledge this is the first description of primary isolated extra-medullary manifestation of a acute myeloid leukemia in the lungs.
Asunto(s)
Líquido del Lavado Bronquioalveolar/citología , Leucemia Mieloide Aguda/patología , Neoplasias Pulmonares/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Crisis Blástica/patología , Citarabina/administración & dosificación , Daunorrubicina/administración & dosificación , Femenino , Humanos , Leucemia Mieloide Aguda/diagnóstico por imagen , Leucemia Mieloide Aguda/tratamiento farmacológico , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/tratamiento farmacológico , Persona de Mediana Edad , Prednisolona/administración & dosificación , Radiografía , Tioguanina/administración & dosificación , Vincristina/administración & dosificaciónRESUMEN
BACKGROUND: CD56 which is considered as a marker of natural killer cells is also expressed in some cases of acute myelogenous leukemia (AML) and is involved in cell adhesion mediating extramedullary leukemic infiltration. CD7/CD56 coexpression has been suggested to be a distinct biological and clinical entity of AML. PATIENT: This is a report of a 53-year-old woman who developed CD7/CD56-positive AML with primary manifestation as intracranial tumor. The patient reported of neurological impairment (impairment of visus and occurrence of double pictures). Cranial computed tomography showed an intracranial tumor, and histological examination exhibited myeloid blast cells. Peripheral leukocyte count at admission was within the normal range (5,32 Gpt/l), and percentage frequency of blasts in the blood smears was 54%. Cytological bone marrow examination showed diffuse infiltration by the same myeloid blast cells. The immunophenotype was CD7/CD13/CD33/CD38/CD56/ HLA-DR-positive. The blast cells were myeloperoxidase-positive but lactoferrin-negative. Thus, diagnosis of acute myeloid leukemia (M2 FAB) was established. Treatment consists of chemotherapy (Ara-C and anthracycline) and local radiation of the intracranial tumor. After treatment patient achieved a complete remission. CONCLUSION: With regard to the literature CD7/CD56-positive AML have a high incidence of central nervous system involvement which should be kept in mind and may be associated to CD56 expression. Copyright 2000 S. Karger GmbH, Freiburg
Asunto(s)
Angioedema/etiología , Proteínas Inactivadoras del Complemento 1/deficiencia , Anabolizantes/uso terapéutico , Angioedema/tratamiento farmacológico , Angioedema/prevención & control , Antifibrinolíticos/uso terapéutico , Proteínas Inactivadoras del Complemento 1/fisiología , Proteínas Inactivadoras del Complemento 1/uso terapéutico , Danazol/uso terapéutico , Antagonistas de Estrógenos/uso terapéutico , Humanos , Inmunosupresores/uso terapéutico , Plasmaféresis , Estanozolol/uso terapéuticoRESUMEN
The detection of dysplastic features of hematopoiesis in de novo acute myeloid leukemia (AML) by light microscopy is defined as AML with trilineage myelodysplasia (AML/TLMD). The prognostic relevance of these dysplastic features for patients with de novo AML remains unclear. In order to evaluate the role of dysplasia in de novo AML, bone marrow aspirates from 69 patients were analyzed prospectively and investigated separately for erythropoiesis, granulopoiesis and megakaryopoiesis by three independent investigators. The overall complete remission (CR) rate was 48.8% and partial remission (PR) or nonresponders constituted 52.2% of the patients investigated. The median overall survival time was 5 months with a disease-free interval of 3.5 months for all patients. Dysgranulopoiesis (DysG) was observed in 30.4%, dysmegakaryopoiesis (DysM) in 50.7%, and dyserythropoiesis (DysE) in 43.5%. Of all patients, 26.0% showed trilineage dysplastic features and were thus classified as AML/TLMD. A significantly worse prognosis (Kaplan-Meyer plot, Student's t-test) was calculated for those patients with detection of only DysG (p = 0.002), DysM (p = 0.02), DysE (p = 0.04) as compared with patients without any dysplastic signs. An unfavorable karyotype was correlated with patients showing DysG (P = 0.02) and DysM (P = 0.04). For these patients with an unfavorable karyotype, the occurrence of any dysplastic features had no additional prognostic impact. Dysplastic features (DysG, DysM, DysE) seem to be an important prognostic factor in de novo AML correlating with short overall survival. DysG and DysM correlated well with the appearance of unfavorable chromosomal abnormalities. It may be reasonable to assume that patients with dysplastic features should be considered for more aggressive treatment schedules at the time of diagnosis.