ABSTRACT
The tyrosine kinase inhibitor dasatinib is approved for Philadelphia chromosome-positive leukemia, including chronic myeloid leukemia (CML). Although effective and well tolerated, patients typically exhibit a transient lymphocytosis after dasatinib uptake. To date, the underlying physiological process linking dasatinib to lymphocytosis remains unknown. Here, we used a small rodent model to examine the mechanism of dasatinib-induced lymphocytosis, focusing on lymphocyte trafficking into and out of secondary lymphoid organs. Our data indicate that lymphocyte homing to lymph nodes and spleen remained unaffected by dasatinib treatment. In contrast, dasatinib promoted lymphocyte egress from spleen with kinetics consistent with the observed lymphocytosis. Unexpectedly, dasatinib-induced lymphocyte egress occurred independently of canonical sphingosine-1-phosphate-mediated egress signals; instead, dasatinib treatment led to a decrease in spleen size, concomitant with increased splenic stromal cell contractility, as measured by myosin light chain phosphorylation. Accordingly, dasatinib-induced lymphocytosis was partially reversed by pharmacological inhibition of the contraction-promoting factor Rho-rho associated kinase. Finally, we uncovered a decrease in spleen size in patients with CML who showed lymphocytosis immediately after dasatinib treatment, and this reduction was proportional to the magnitude of lymphocytosis and dasatinib plasma levels. In summary, our work provides evidence that dasatinib-induced lymphocytosis is a consequence of drug-induced contractility of splenic stromal cells.
Subject(s)
Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Lymphocytosis , Humans , Dasatinib/adverse effects , Lymphocytosis/chemically induced , Lymphocytosis/pathology , Spleen/pathology , Pyrimidines/adverse effects , Thiazoles/adverse effects , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathologyABSTRACT
We report the case of a 29-year-old male with structuring ileocolic Crohn's disease (CD), diagnosed in 2007 and treated with oral azathioprine, oral mesalazine and intravenous infliximab, without any other surgical or medical history of interest. He presented to the Emergency Room with abdominal distention and pain, nausea, vomiting and motility problems of a three-day duration. An abdominal computerized tomography using intravenous contrast was performed.
Subject(s)
Crohn Disease/diagnostic imaging , Tomography, X-Ray Computed , Adult , Constriction, Pathologic/diagnostic imaging , Constriction, Pathologic/etiology , Crohn Disease/complications , Humans , MaleABSTRACT
The use of the new direct-action antivirals against hepatitis C virus provides very high viral eradication rates. However, various recently published articles recommend caution with their use after the appearance of some cases of de novo tumors (originated in hepatic and extra-hepatic locations) and a possible shorter time period of recurrence of hepatocellular carcinomas previously treated with surgery or loco-regional therapies. The sudden drop of the number of natural killer cells secondary to the use of these new medicines has been suggested as one of the possible mechanisms responsible for this process. However, due to the controversy concerning this subject and the absence of long-term follow-up studies in clinical practice, caution is needed before definitive conclusions are settled. We present the case report of a patient diagnosed of chronic liver disease secondary to hepatitis C virus infection and a past history of hepatocellular carcinoma in complete remission after radiofrequency ablation. He was treated with the new direct-action antivirals reaching sustained viral response. Six months later, the patient was diagnosed with liver metastasis from a small-cell neuroendocrine tumor of unknown primary site.
Subject(s)
Antiviral Agents/adverse effects , Carcinoma, Neuroendocrine/pathology , Carcinoma, Neuroendocrine/secondary , Hepatitis C/drug therapy , Liver Neoplasms/secondary , Aged , Carcinoma, Hepatocellular/pathology , Hepatitis C/complications , Humans , Liver Cirrhosis/etiology , Liver Cirrhosis/pathology , Liver Neoplasms/pathology , MaleABSTRACT
Radiologists seldom encounter parasitic diseases in their daily practice in most of Europe, although the incidence of these diseases is increasing due to migration and tourism from/to endemic areas. Moreover, some parasitic diseases are still endemic in certain European regions, and immunocompromised individuals also pose a higher risk of developing these conditions. This article reviews and summarises the imaging findings of some of the most important and frequent human parasitic diseases, including information about the parasite's life cycle, pathophysiology, clinical findings, diagnosis, and treatment. We include malaria, amoebiasis, toxoplasmosis, trypanosomiasis, leishmaniasis, echinococcosis, cysticercosis, clonorchiasis, schistosomiasis, fascioliasis, ascariasis, anisakiasis, dracunculiasis, and strongyloidiasis. The aim of this review is to help radiologists when dealing with these diseases or in cases where they are suspected. Teaching Points ⢠Incidence of parasitic diseases is increasing due to migratory movements and travelling. ⢠Some parasitic diseases are still endemic in certain regions in Europe. ⢠Parasitic diseases can have complex life cycles often involving different hosts. ⢠Prompt diagnosis and treatment is essential for patient management in parasitic diseases. ⢠Radiologists should be able to recognise and suspect the most relevant parasitic diseases.
ABSTRACT
Abdominal complications affect more than 80% of patients who undergo hematopoietic stem cell transplantation (HSCT) for treatment of benign or malignant hematologic disease and some solid tumors. HSCT can be performed using cells from bone marrow, peripheral blood, or umbilical cord blood. These stem cells may be from the patient him- or herself (autologous transplant), from relatives or nonrelatives with very similar human leukocyte antigen (allogeneic transplant), or from an identical twin (syngeneic transplant). Posttransplantation complications are classified according to the amount of time elapsed between transplantation and onset. Complications that occur during the first 100 days are divided into preengraftment phase complications (≤30 days after transplantation) and early posttransplantation phase complications (31-100 days after transplantation) and include infectious and noninfectious conditions such as hepatic veno-occlusive disease (VOD), hemorrhagic cystitis, neutropenic colitis, benign pneumatosis, and acute graft-versus-host disease (GVHD). Hepatic VOD, neutropenic colitis, and acute hemorrhagic cystitis are associated with the pretransplantation conditioning regimen. After the first 100 days, chronic GVHD and lymphoproliferative disease are the main complications. Computed tomography and ultrasonography are the primary imaging techniques used in HSCT patients and can help make an early diagnosis, grade the severity of impact, and (if necessary) recommend further investigations to confirm the diagnosis.
Subject(s)
Hematopoietic Stem Cell Transplantation/adverse effects , Abdomen , Digestive System Diseases/diagnosis , Digestive System Diseases/etiology , Humans , Tomography, X-Ray Computed , Urologic Diseases/diagnosis , Urologic Diseases/etiologyABSTRACT
Fundamento y objetivo: Analizar prospectivamente la precisión de la tomografía por emisión de positrones/tomografía computarizada (PET/TC) frente al patrón oro en la estadificación inicial de los pacientes con linfoma no hodgkiniano (LNH) e identificar el protocolo técnico más adecuado.Pacientes y método: Estudio transversal prospectivo de 76 pacientes diagnosticados de LNH durante 3 años consecutivos en el Hospital Universitario La Paz de Madrid no tratados previamente. Todos los pacientes fueron estudiados con la técnica PET/TC: inicialmente se obtuvo una TC de dosis baja, después el escáner de emisión de la PET y posteriormente un estudio de TC de dosis alta con contraste intravenoso. Se reconstruyeron dos estudios de PET/TC para cada paciente: uno de PET/TC de dosis baja (PET/TC DB) y otro de PET/TC de dosis alta (PET/TC DA). Cada modalidad de PET/TC fue evaluada en consenso por un equipo de médico nuclear y radiólogo, diferente para cada una de las modalidades. Las imágenes de TC y de PET fueron interpretadas por separado por otro radiólogo y otro médico nuclear independientes.Resultados: La concordancia con el patrón de referencia fue en el 52,2% de los pacientes (κ=0,458) para la TC, 46% para la PET (κ=0,335), 75% para la PET/TC DB (κ=0,664) y 76,8% para la PET/TC DA (κ=0,679), con p<0,001. Todas las técnicas infravaloraron el estadio (p<0,05), aunque con la PET/TC DA en un menor porcentaje de pacientes (20,3%). Conclusión: La PET/TC es superior en la estadificación inicial de los pacientes con LNH, siendo la PET/TC DA la técnica más precisa de las que hemos estudiado (AU)
Background and objective: To prospectively analyze the diagnostic accuracy of PET/CT in non-Hodgkin's lymphoma (NHL) and to evaluate the most appropriate study protocol of this technique.Patients and method: Seventy-six biopsy proven NHL patients were enrolled in this prospective study for 3 years. Patients initially underwent a low-dose CT without intravenous contrast, then a PET emission scan and finally a full-dose CT with intravenous contrast. For every patient, two modalities of PET/CT images were reconstructed: a low-dose unenhanced PET/CT and a full-dose enhanced PET/CT. Each modality was evaluated by either of two pairs of readers, different for each modality. Enhanced CT and PET images were evaluated by an independent radiologist and nuclear medicine physician respectively.Results: Agreement between reference standard and techniques was as follows: 52.2% of patients with enhanced CT (κ=0.458), 46% with PET (κ=0.335), 75% with low-dose unenhanced PET/CT (κ=0.664) and 76.8% with full-dose enhanced PET/CT (κ=0.679), with p<0.001. Although all techniques underestimated the stage in comparison to gold standard, the lowest percentage was for full-dose enhanced PET/CT (20.3%).Conclusions: PET/CT improved staging accuracy of NHL, being full-dose enhanced PET/CT the most accurate technique in our study (AU)
Subject(s)
Humans , Positron-Emission Tomography/methods , Lymphoma, Non-Hodgkin/pathology , /methods , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic useABSTRACT
BACKGROUND AND OBJECTIVE: To prospectively analyze the diagnostic accuracy of PET/CT in non-Hodgkin's lymphoma (NHL) and to evaluate the most appropriate study protocol of this technique. PATIENTS AND METHOD: Seventy-six biopsy proven NHL patients were enrolled in this prospective study for 3 years. Patients initially underwent a low-dose CT without intravenous contrast, then a PET emission scan and finally a full-dose CT with intravenous contrast. For every patient, two modalities of PET/CT images were reconstructed: a low-dose unenhanced PET/CT and a full-dose enhanced PET/CT. Each modality was evaluated by either of two pairs of readers, different for each modality. Enhanced CT and PET images were evaluated by an independent radiologist and nuclear medicine physician respectively. RESULTS: Agreement between reference standard and techniques was as follows: 52.2% of patients with enhanced CT (κ=0.458), 46% with PET (κ=0.335), 75% with low-dose unenhanced PET/CT (κ=0.664) and 76.8% with full-dose enhanced PET/CT (κ=0.679), with p<0.001. Although all techniques underestimated the stage in comparison to gold standard, the lowest percentage was for full-dose enhanced PET/CT (20.3%). CONCLUSIONS: PET/CT improved staging accuracy of NHL, being full-dose enhanced PET/CT the most accurate technique in our study.
Subject(s)
Lymphoma, Non-Hodgkin/pathology , Multimodal Imaging , Neoplasm Staging/methods , Adolescent , Adult , Aged , Biomarkers, Tumor/blood , Bone Marrow Examination , Contrast Media , Cross-Sectional Studies , Female , Fluorine Radioisotopes , Fluorodeoxyglucose F18 , Humans , Lymphoma, Non-Hodgkin/blood , Lymphoma, Non-Hodgkin/diagnostic imaging , Male , Middle Aged , Neoplasm Staging/standards , Nuclear Medicine , Observer Variation , Physical Examination , Positron-Emission Tomography , Prospective Studies , Radiology , Radiopharmaceuticals , Reference Standards , Reproducibility of Results , Tomography, X-Ray Computed , Young AdultABSTRACT
BACKGROUND: The real accuracy of computed tomographic colonography (CTC) is still unknown. OBJECTIVE: To perform a meta-analysis of the diagnostic accuracy of CTC for the detection of polyps and colorectal tumors. SELECTION OF STUDIES: Studiesassessing the accuracy of CTC for the detection of colorectal polyps and tumors were selected. data synthesis: Meta-analyses combining sensitivities, specificities and likelihood ratios (LRs) for the diagnosis of polyps and colorectal tumors were carried out. RESULTS: Forty-seven studies, providing data of 10,546 patients, were included. Overall per-polyp sensitivity of CTC was 66% (64-68%), for polyps 6-9 mm in size it was 59% (56-61%), and 76% (73-79%) for polyps larger than 9 mm. Overall per-patient sensitivity was 69% (66-72%), for polyps 6-9 mm 60% (56-65%), and 83% (70-85%) for lesions larger than 9 mm. Overall CTC specificity was 83% (81-84%). Positive and negative LRs were 2.9 (1.8-4) and 0.38 (0.27-0.53), respectively; for polyps 6-9 mm in size, they were 3.8 (2.5-5.7) and 0.4 (0.27-0.59), and 12.3 (7.7-19.4) and 0.19 (0.12-0.3) for polyps larger than 9 mm. CONCLUSION: CTC is highly specific for the detection of colorectal polyps and tumors. Some studies reported high sensitivities, but the results of the studies were highly heterogeneous, while the studied variables explained only part of this discrepancy.
