RESUMEN
Venous thromboembolism (VTE) is a common complication of cancer patients. Initiation of anticoagulant treatment is of vital importance once a diagnosis of VTE has been established. Unfractionated heparin and low-molecular-weight heparins (LMWH) have been the mainstay for in-hospital-based prophylaxis, both postsurgically and on medicine floors, and for the acute management of VTE. The current international guidelines, including American Society of Clinical Oncology, the American College of Chest Physicians, the European Society of Medical Oncology, and the International Society of Thrombosis and Hemostasis, recommend the use of LMWH monotherapy for the long-term management of cancer patients with established acute symptomatic VTE. Although LMWHs have become the preferred treatment for patients with cancer, problems with its use have prompted clinicians to seek newer antithrombotic agents.
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Anticoagulantes/administración & dosificación , Neoplasias/sangre , Tromboembolia Venosa/tratamiento farmacológico , Humanos , Neoplasias/patología , Ensayos Clínicos Controlados Aleatorios como Asunto , Tromboembolia Venosa/sangre , Tromboembolia Venosa/patologíaRESUMEN
The use of new oral anticoagulants (NOACs) is expected to rise significantly in upcoming years. Therefore, it is important to understand the potential uses, side effects, and management of these agents in routine practice. NOACs have major pharmacologic advantages over warfarin, including a rapid onset and offset of action, fewer drug interactions, and predictable pharmacokinetics. These agents are gaining popularity among both physicians and patients because of their ease of administration and the advantage of eliminating the requirement for regular coagulation monitoring. NOACs work to prevent and treat thrombosis by targeting either thrombin (as with dabigatran) or factor Xa (as with rivaroxaban and apixaban). In this review, we discuss practical recommendations for the use of NOACs and the risks and benefits of incorporating them into routine practice.
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Anticoagulantes/uso terapéutico , Dabigatrán/uso terapéutico , Pirazoles/uso terapéutico , Piridonas/uso terapéutico , Rivaroxabán/uso terapéutico , Trombosis/tratamiento farmacológico , Administración Oral , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Anticoagulantes/farmacología , Coagulación Sanguínea/efectos de los fármacos , Dabigatrán/administración & dosificación , Dabigatrán/efectos adversos , Dabigatrán/farmacología , Interacciones Farmacológicas , Humanos , Pirazoles/administración & dosificación , Pirazoles/efectos adversos , Pirazoles/farmacología , Piridonas/administración & dosificación , Piridonas/efectos adversos , Piridonas/farmacología , Rivaroxabán/administración & dosificación , Rivaroxabán/efectos adversos , Rivaroxabán/farmacología , Trombosis/prevención & controlRESUMEN
Lung cancer is considered the number one killer among all cancers. Recent observations have altered the treatment paradigm for non-small-cell lung cancer (NSCLC). The discovery of activating mutations in the epidermal growth factor receptor and anaplastic lymphoma kinase positivity has made personalized treatment for NSCLC more feasible. Both erlotinib and crizotinib have been shown to be effective and safe for subgroup populations, and now personalized treatment for nonsquamous NSCLC has progressed even further. New tyrosine kinase inhibitors are being tested, resistant mutations are being studied, and new detection systems are being incorporated; all these developments will make the detection and treatment of the deadliest cancer more affordable, practical, and effective. The National Comprehensive Cancer Network has already incorporated these new developments into their guidelines for advanced nonsquamous NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Animales , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Crizotinib , Clorhidrato de Erlotinib , Humanos , Neoplasias Pulmonares/metabolismo , Terapia Molecular Dirigida , Pirazoles/uso terapéutico , Piridinas/uso terapéutico , Quinazolinas/uso terapéuticoRESUMEN
Hepatitis B virus (HBV) infection is a potentially life-threatening condition that can be effectively prevented by vaccination. In the United States, more than 1.5 million people are infected with HBV, and that number continues to rise with the arrival of immigrants from HBV-endemic countries. Cancer is the second leading cause of death in the United States; 1 in 2 men and women will be diagnosed during their lifetime, and a large proportion of them will require chemotherapy. Chemotherapy-induced immunosuppression can result in HBV reactivation in asymptomatic HBV carriers or patients with resolved HBV infection, causing severe morbidity and mortality. The rate of HBV reactivation depends on several factors, including host and viral factors, and varies from 3-88%. Mortality rates in HBV reactivation range from 23-71%. However, a recent US survey showed that 20% of practicing oncologists never perform any type of HBV screening before the initiation of chemotherapy, and less than 40% perform HBV screening in patients who have high-risk factors for HBV or a history of hepatitis. Given the magnitude of this clinical problem, it is very important to increase awareness among physicians regarding this potentially life-threatening complication. In this article, we review the current understanding of the problem, discuss the existing guidelines from professional societies, and outline a management plan.
Asunto(s)
Virus de la Hepatitis B/fisiología , Hepatitis B/complicaciones , Hepatitis B/prevención & control , Neoplasias/complicaciones , Activación Viral , Profilaxis Antibiótica , Antineoplásicos/uso terapéutico , Antivirales/uso terapéutico , Hepatitis B/diagnóstico , Hepatitis B/epidemiología , Humanos , Incidencia , Neoplasias/tratamiento farmacológico , Neoplasias/virología , Factores de RiesgoRESUMEN
Objectives Metaplastic breast cancer (MBC) is a rare neoplasm accounting for <1% of all breast cancer. We evaluated the clinical characteristics and survival outcomes of MBC. Methods Patients diagnosed with pathologically proven MBC were reviewed from the institutional breast cancer database from 2000 to 2017. Results A total of 136 patients diagnosed with MBC were included in the study. The median age of the diagnosis was 60 years, and 60% of patients were stage II at diagnosis, and 22% were stage III. About two-thirds of the patients were triple-negative; 93% had nuclear grade III, and 25% had a lymphovascular invasion. Squamous differentiation (29%) was the most common histologic subtype, followed by the spindle subtype (21%). The most common distant metastases were lung (22%), followed by bone (13%). Moreover, 60% had a mastectomy, 19% had endocrine therapy, 58% had radiation, 51% received anthracycline-based chemotherapy, 26% had non-anthracycline chemotherapy, and 22% received no chemotherapy. In the entire cohort, the two-year overall survival (OS) and five-year OS were 79% and 69%, respectively, and the two-year progression-free survival (PFS) and five-year PFS were 72% and 61%, respectively. On multivariable analysis, the stage of MBC (stage III: hazard ratio (HR), 5.065 (95% confidence interval (CI), 1.02-25.27) (p=0.048)), poor functional status (Eastern Cooperative Oncology Group (ECOG) score, 2; HR, 24.736 (95% CI, 1.92-318.73) (p=0.014)), and distant metastasis to the brain (HR, 8.453 (95% CI, 1.88-38.04) (p=0.005)) and lung (HR, 42.102 (95% CI, 7.20-246.36) (p<0.001)) were significant predictors of decreased OS. Conclusions MBC demonstrated early disease progression and poor overall survival. The stage of MBC, decreased performance status, and metastasis to the lung and brain were independent poor prognostic factors.
RESUMEN
The incidence of pulmonary toxicities with the use of tyrosine kinase inhibitors (TKIs) is not very high; however, various case reports and studies continue to show significant variability in the incidence of these adverse events, ranging from 0.2% to 10.9%. Gefitinib and erlotinib are orally active, small-molecule inhibitors of the epidermal growth factor receptor tyrosine kinase that are mainly used to treat non-small cell lung cancer. Imatinib is an inhibitor of BCR-ABL tyrosine kinase that is used to treat various leukemias, gastrointestinal stromal tumors, and other cancers. In this article, we review data to identify the very rare but fatal pulmonary toxicities (mostly interstitial lung disease) caused by these drugs.
Asunto(s)
Antineoplásicos/efectos adversos , Enfermedades Pulmonares Intersticiales/inducido químicamente , Inhibidores de Proteínas Quinasas/efectos adversos , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Benzamidas/administración & dosificación , Benzamidas/efectos adversos , Benzamidas/uso terapéutico , Receptores ErbB/antagonistas & inhibidores , Clorhidrato de Erlotinib , Proteínas de Fusión bcr-abl/antagonistas & inhibidores , Gefitinib , Humanos , Mesilato de Imatinib , Enfermedades Pulmonares Intersticiales/mortalidad , Neoplasias/tratamiento farmacológico , Piperazinas/administración & dosificación , Piperazinas/efectos adversos , Piperazinas/uso terapéutico , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirimidinas/administración & dosificación , Pirimidinas/efectos adversos , Pirimidinas/uso terapéutico , Quinazolinas/administración & dosificación , Quinazolinas/efectos adversos , Quinazolinas/uso terapéuticoRESUMEN
With the advancement of research in cancer treatment more and more drugs are being introduced for the treatment of cancer. In this review study, we have tried to look at some of the relatively newly introduced drugs, commonly referred to as biologics. The aim of this study was to review the very rare but fatal pulmonary toxicities (mostly interstitial lung disease) caused by these drugs. The drugs that were reviewed are rituximab, cetuximab, bevacizumab, alemtuzumab, and trastuzumab. This review basically aims at presenting a basic introduction (mechanism of action and indications of use) of these drugs followed by a summary of the incidence, various clinical presentations, diagnosis, treatment options, and outcome of patients around the world who presented with pulmonary toxicities caused by these drugs.
Asunto(s)
Antineoplásicos/efectos adversos , Enfermedades Pulmonares Intersticiales/inducido químicamente , Pulmón/efectos de los fármacos , Humanos , Neoplasias/tratamiento farmacológicoRESUMEN
BACKGROUND: Aromatase inhibitors (AIs) are an effective treatment for postmenopausal women with hormone receptor-positive breast cancer. However, patients receiving AIs report a higher incidence of musculoskeletal symptoms and bone fractures; the mechanism and risk factors for this correlation are not well studied. The aim of this study was to correlate these musculoskeletal symptoms and bone fractures in patients receiving AIs with bone mineral density (BMD), previous tamoxifen use, and administration of calcium/bisphosphonate (Ca/Bis). PATIENTS AND METHODS: We reviewed charts of 856 patients with hormone receptor-positive nonmetastatic breast cancer seen at our institution between January 1999 and October 2007. A total of 316 patients met the inclusion criteria of treatment with one of the AIs for > or = 3 months and availability of a dualenergy X-ray absorptiometry (DEXA) during this treatment. Arthralgia, generalized bone pain and/or myalgia, bone fracture after beginning AIs, any tamoxifen treatment, and Ca/Bis therapy were recorded. RESULTS: Our study demonstrates a significant association between symptoms and DEXA-BMD results (P < .001). Similarly, the group receiving tamoxifen before AIs had fewer patients with arthralgia or generalized bone pain/myalgia or bone fracture (P < .001). Furthermore, the group receiving AIs plus Ca/Bis had more patients without musculoskeletal symptoms and had fewer fractures. Finally, the group receiving steroidal AIs compared with nonsteroidal AIs had more patients with arthralgia or generalized bone pain and/or myalgia, and bone fractures (P < .001). CONCLUSION: Patients on AIs who develop osteoporosis are at increased risk of musculoskeletal symptoms and bone fracture. Comedication with Ca/Bis reduces the likelihood for osteoporosis and musculoskeletal symptoms. Patients who received tamoxifen before AIs were less likely to develop AI-related musculoskeletal symptoms. We recommend that patients on AIs should be offered Ca/Bis to reduce the incidence of musculoskeletal symptoms and fracture, especially if patients are receiving steroidal AI and/or did not receive tamoxifen before AIs.
Asunto(s)
Inhibidores de la Aromatasa/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Enfermedades Musculoesqueléticas/inducido químicamente , Osteoporosis/prevención & control , Absorciometría de Fotón , Anciano , Antineoplásicos Hormonales/uso terapéutico , Densidad Ósea/efectos de los fármacos , Neoplasias de la Mama/patología , Fosfatos de Calcio/administración & dosificación , Difosfonatos/administración & dosificación , Femenino , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Tamoxifeno/uso terapéuticoRESUMEN
Monoclonal gammopathy of undetermined significance (MGUS) is defined by the presence of a serum M-protein at a concentration of 3 g/dL or less, with less than 10% plasma cells in the bone marrow, and the absence of lytic bone lesions, anemia, hypercalcemia, and renal insufficiency related to the plasma cell proliferative process. The annual risk of MGUS progressing to a symptomatic plasma cell proliferation or other related malignancy is approximately 1%. The association between malignancy and venous thromboembolism (VTE) is well recognized. In this retrospective study of MGUS patients, VTE was seen in 8% (9/112) of patients, a rate that is 22.8-fold higher than that in the general population (P is less than .001). Although many studies have identified VTE as a marker for subsequent malignancy, we did not find a significant difference in the incidence of VTE as a function of the risk factor group.
Asunto(s)
Gammopatía Monoclonal de Relevancia Indeterminada/complicaciones , Tromboembolia Venosa/epidemiología , Progresión de la Enfermedad , Humanos , Gammopatía Monoclonal de Relevancia Indeterminada/mortalidad , Estudios Retrospectivos , Medición de Riesgo , Tasa de Supervivencia , Tromboembolia Venosa/mortalidad , Tromboembolia Venosa/prevención & controlRESUMEN
Background Ibrutinib is a Bruton's tyrosine kinase inhibitor, which is United States Food and Drug Administration (FDA)-approved for chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenström's macroglobulinemia. Ibrutinib is associated with atrial fibrillation and bleeding events. Our aim is to determine the management of prior atrial fibrillation when starting ibrutinib, as well as ibrutinib-induced atrial fibrillation. Our focus is on which rate and rhythm control strategies to use and decisions regarding the use of antiplatelet and anticoagulation agents. Materials and Methods We conducted a retrospective descriptive study of case records over a three-year period from February 2014 to February 2017. We reviewed 597 patient charts from the Cleveland Clinic database. Ibrutinib was started in 43 patients. Of those, 10 had atrial fibrillation prior to starting ibrutinib and four developed atrial fibrillation while on ibrutinib. Data was collected for demographic details, co-morbid conditions, CHA2DS2-VASc (congestive heart failure, hypertension, age, diabetes mellitus, prior stroke, transient ischemic attack or thromboembolism, vascular disease, age, and sex category) score, HAS-BLED (hypertension, abnormal renal and liver function, stroke, bleeding, labile INR, elderly, and drugs or alcohol) score, and drugs used for antiplatelet effects, for anticoagulation, and for rate and rhythm control. Outcomes for embolic and bleeding events were assessed. Results Of the 43 patients, 14 (32.5%) had or developed atrial fibrillation; 10 (23.26%) had prior atrial fibrillation, and four (9.30%) developed atrial fibrillation after starting ibrutinib. The majority were males (71.42%) and Caucasian (71.42%). The disease breakdown was chronic lymphocytic leukemia (42.86%), mantle cell lymphoma (50%), and Waldenström's macroglobulinemia (7.14%). The mean starting dose of ibrutinib in patients with prior atrial fibrillation was 569 mg and for patients who developed atrial fibrillation was 420 mg. In the 10 patients who had atrial fibrillation prior to ibrutinib, all 10 were on beta blockers, one was on diltiazem, three were on amiodarone, one was on flecainide, one was on digoxin, and one was on Tikosyn® (Pfizer, Inc., New York, NY). The ibrutinib dose was decreased/discontinued in two patients. In patients who developed atrial fibrillation after starting ibrutinib, three were on beta blockers, two on amiodarone, and one on Tikosyn. Ibrutinib was discontinued in one patient. In patients who had prior atrial fibrillation, three were on warfarin, one on enoxaparin, and two on apixaban. In three patients, aspirin and enoxaparin were discontinued. In patients who developed atrial fibrillation after starting ibrutinib, enoxaparin was given to two and apixaban to one. None of the patients had a stroke, transient ischemic attack (TIA), or bleeding events. Conclusions From our study, we concluded that ibrutinib can be safely given in the presence of atrial fibrillation, and when atrial fibrillation was induced, we further concluded that beta blockers were the preferred agents for rate control. Ibrutinib has many drug interactions with other rate and rhythm control agents; hence, their use was lower. When atrial fibrillation was uncontrolled, ibrutinib was temporarily held and then cautiously restarted. The decision to start or adjust anticoagulation depended on the bleeding and stroke risks as assessed by their physicians.
RESUMEN
There are many novel chemotherapeutic options and targeted therapies available for the treatment of colorectal and pancreatic cancer. Patients with these cancers often have hepatic impairment either from the metastasis to the liver or from the chemotherapy or targeted therapies used to treat the disease. It is important to describe the effects of these agents in patients with hepatic impairment. This article will review the dosage recommendations for the chemotherapy regimens and targeted therapies in colorectal and pancreatic cancer patients in the setting of hepatic impairment.
RESUMEN
An 83-year-old man was diagnosed with stage 4 prostate cancer with a Gleason score of 7 (3+4). His initial prostate-specific antigen (PSA) level was 965 ng/dL, and he demonstrated extensive metastatic disease of the thoracic spine. After an initial response to monthly leuprolide injections, his PSA level began to increase and bicalutamide was added. An initial decrease in his PSA level was observed; however, the level gradually rose to 212 ng/dL and bicalutamide was discontinued. Three months later, his PSA level was <0.05 ng/dL and has remained <1 ng/dL for the past 27 months. Bicalutamide withdrawal usually leads to transient remission, with PSA level dropping to approximately 50% of the initial level. The duration of the remission is usually limited to approximately 6 months. However, the sustained response that was observed in our patient suggests that a trial of androgen withdrawal, even in the setting of rising PSA levels, might be reasonable before initiating more toxic therapies.
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Adenocarcinoma/tratamiento farmacológico , Antagonistas de Andrógenos/administración & dosificación , Anilidas/administración & dosificación , Nitrilos/administración & dosificación , Neoplasias de la Próstata/tratamiento farmacológico , Compuestos de Tosilo/administración & dosificación , Adenocarcinoma/sangre , Adenocarcinoma/secundario , Anciano , Anciano de 80 o más Años , Humanos , Masculino , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/patología , Inducción de Remisión , Estudios RetrospectivosRESUMEN
BACKGROUND: Cardiac sarcomas are rare and have a poor prognosis. The median overall survival remains dismal and has been reported ranging from 6 months to a few years. Primary cardiac sarcoma is the most common malignant tumor comprising approximately 95% of all malignant tumors of the heart. METHODS: We conducted a retrospective chart review in a single institution of patients diagnosed between March 1988 and April 2013. A total of 42 patients were identified. The following variables were studied: age at diagnosis, year of diagnosis, sex, stage, site of tumor involvement, tumor histology, grade, treatment modality, type of chemotherapy, and survival outcome. The overall median follow-up time was 49.5 months. RESULTS: The most common histologic type was angiosarcoma. Overall estimated median survival (EMS) was 25 months. Tumors involving the left side of the heart and pericardium demonstrated better survival. Patients who received multimodality treatment (any combination of surgery, radiation therapy, and chemotherapy) had an EMS of 36.5 months compared with 14.1 months for patients treated with surgery, radiation therapy, or chemotherapy only (P=0.05). CONCLUSIONS: Cardiac sarcoma is a lethal tumor with an EMS of 25 months. The tumor histology could be a possible predictor of better survival. Although selection bias may have been present, multimodality therapy (surgery, radiation therapy, and chemotherapy) was associated with improved survival.
Asunto(s)
Neoplasias Cardíacas/mortalidad , Neoplasias Cardíacas/terapia , Sarcoma/mortalidad , Sarcoma/terapia , Centros Médicos Académicos , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Instituciones Oncológicas , Quimioterapia Adyuvante , Estudios de Cohortes , Terapia Combinada , Bases de Datos Factuales , Supervivencia sin Enfermedad , Femenino , Neoplasias Cardíacas/patología , Hemangiosarcoma/mortalidad , Hemangiosarcoma/patología , Hemangiosarcoma/terapia , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Invasividad Neoplásica/patología , Estadificación de Neoplasias , Ohio , Pronóstico , Radioterapia Adyuvante , Estudios Retrospectivos , Sarcoma/patología , Estadísticas no Paramétricas , Análisis de Supervivencia , Cirugía Torácica/métodos , Resultado del Tratamiento , Adulto JovenRESUMEN
Lung cancer is the leading cause of cancer-related death in both developed and developing countries with unacceptably high mortality even for early-stage cancers. Present guidelines do not recommend adjuvant chemotherapy for stage I non-small cell lung carcinoma and prompts a search for a prognostic marker that would separate stage I patients into 2 groups, those who would benefit and those who would not benefit from adjuvant treatment. Studies during the last decade showed that the gene expression profiling can be the biomarker being sought. Many gene expression profiling have been found and reported from the analysis of surgical specimens of resected lung cancers during the last decade, and many of them had been shown to have an excellent predictive accuracy. These profiles used in the studies had not only different gene combinations but also different number of genes and methods of identification. Researchers have used microarray assays, RT-quantitative polymerase chain reaction, and more recently microRNA-based techniques to achieve this goal. Unfortunately, most of the profiles were not sufficiently validated and/or were not used in prospective phase III studies. This review focuses on major studies in the field, future prospects, as well as the lessons learned so far. It is shown that the gene expression profiles have a good chance of being implemented in future everyday practice.
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Adenocarcinoma/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Células Escamosas/genética , Regulación Neoplásica de la Expresión Génica/genética , Neoplasias Pulmonares/genética , ARN Mensajero/genética , Adenocarcinoma/patología , Adenocarcinoma/terapia , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/terapia , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Quimioterapia Adyuvante/métodos , Perfilación de la Expresión Génica/métodos , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , MicroARNs/genética , Estadificación de Neoplasias , Selección de Paciente , Neumonectomía , Pronóstico , Análisis por Matrices de Proteínas , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Cutaneous lymphoid hyperplasia (CLH) has been proposed to be the benign end of a continuum of lymphoproliferative disorders with cutaneous lymphoma at its malignant extreme. An intermediate condition, known as "clonal CLH," was first recognized by us and shown to be a transitional state capable of eventuating in overt lymphoma. To better determine the prevalence of dominant clonality and risk of lymphoma among CLH cases, we studied the immunohistology and clonality of fresh-frozen samples from 44 CLH patients referred to a multidisciplinary cutaneous lymphoproliferative disorders program. Using a large panel of lymphoid markers, the cases were divided into 38 typical mixed B-cell/T-cell type CLH and 6 T-cell-rich type (T-CLH), the latter containing > 90% T cells. Of the 44 patients, 38 had solitary or localized lesions (4 cases of T-CLH), and 6 had regional/generalized lesions (2 cases of T-CLH). Forty cases were of idiopathic etiology. Suspected etiologies among 4 other cases included mercuric tattoo pigment, doxepin, clozapine, and bacterial infection. Immunoglobulin heavy chain (IgH) and T-cell receptor (TCR)-gamma gene rearrangements (GR) were studied using polymerase chain reaction assays, which are approximately 80% sensitive. Overall, 27 cases (61%) showed clonal CLH: 12 IgH+ (27%; 3 cases of T-CLH); 13 TCR+ (30%; 1 case of T-CLH); and 2 IgH+/TCR+ (4%; neither case was T-CLH). Two cases (4%; 1 case of T-CLH) progressed to cutaneous B-cell lymphoma. Both of these patients presented with regional lesions. Our findings indicate that clonal overgrowth is common in CLH, links CLH to lymphoma, and probably involves both B- and T-cell lineages (although TCR GR by B cells and vice versa could not be ruled out). The high prevalence of dominant clonality in our series may have resulted from the sensitivity of our PCR assays as well as patient selection.
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Linfocitos/patología , Linfoma/patología , Lesiones Precancerosas/patología , Neoplasias Cutáneas/patología , Algoritmos , Linfocitos B/metabolismo , Linfocitos B/patología , Biomarcadores de Tumor/metabolismo , Células Clonales , ADN de Neoplasias/análisis , Reordenamiento Génico de Linfocito T , Humanos , Hiperplasia , Cadenas Pesadas de Inmunoglobulina/genética , Linfocitos/metabolismo , Linfoma/genética , Linfoma/metabolismo , Reacción en Cadena de la Polimerasa , Lesiones Precancerosas/genética , Lesiones Precancerosas/metabolismo , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/metabolismo , Linfocitos T/metabolismo , Linfocitos T/patologíaRESUMEN
O6-Benzylguanine and its metabolite, 8-oxo-O6-benzylguanine, are equally potent inhibitors of the DNA repair enzyme, O6-alkylguanine-DNA alkyltransferase. Pharmacokinetic values are derived from cancer patients participating in a phase I trial (10 or 20 mg/m2 of O6-benzylguanine in a single bolus dose or 10 to 120 mg/m2 as a 60-min constant infusion). A two-compartment model fits the plasma concentration versus time profile of O6-benzylguanine. O6-Benzylguanine is eliminated rapidly from the plasma compartment in humans (t1/2 alpha and t1/2 beta are 2 +/- 2 min and 26 +/- 15 min [mean +/- SD, n = 7], respectively), and its plasma clearance (513 +/- 148 mL/min/m2) is not dose dependent. Metabolite kinetics are evaluated using both a novel approach describing the relationship between O6-benzylguanine and 8-oxo-O6-benzylguanine and classical metabolite kinetics methods. With increasing doses of O6-benzylguanine, the plasma clearance of 8-oxo-O6-benzylguanine, decreases, prolonging elimination of the metabolite. This effect is not altered by coadministration of BCNU. The urinary excretion of drug and metabolites is minimal.
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Inhibidores Enzimáticos/farmacocinética , Guanina/análogos & derivados , Guanina/metabolismo , Guanina/farmacocinética , Neoplasias/metabolismo , Anciano , Antineoplásicos Alquilantes/uso terapéutico , Carmustina/uso terapéutico , Inhibidores Enzimáticos/metabolismo , Inhibidores Enzimáticos/farmacología , Femenino , Guanina/sangre , Semivida , Humanos , Infusiones Intravenosas , Masculino , Tasa de Depuración Metabólica , Persona de Mediana Edad , Modelos Biológicos , Neoplasias/tratamiento farmacológico , O(6)-Metilguanina-ADN Metiltransferasa/antagonistas & inhibidoresRESUMEN
Small-cell carcinoma of the urinary bladder is a rare and aggressive type of bladder cancer that has a poor prognosis. The incidence has been gradually increasing because of the aging population. Owing to its rarity there are no available treatment guidelines. Several retrospective studies and 1 prospective study have provided some insight into therapy for this disease. A multimodal approach that includes chemotherapy, local radiation therapy, and definitive surgery in resectable cases appears to be an optimal management approach.
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Carcinoma de Células Pequeñas , Terapia Combinada , Neoplasias de la Vejiga Urinaria , Carcinoma de Células Pequeñas/epidemiología , Carcinoma de Células Pequeñas/mortalidad , Carcinoma de Células Pequeñas/terapia , Humanos , Masculino , Pronóstico , Estudios Prospectivos , Estudios Retrospectivos , Factores de Riesgo , Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/epidemiología , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/terapiaRESUMEN
Immune thrombocytopenia (ITP) in adults is a chronic disease resulting from increased platelet destruction and impaired platelet production. Splenectomy remains the most effective and durable treatment in cases that are refractory to first-line therapy, but its use has declined because of the availability of alternate medical therapy, the associated risk of infection, and concern for surgery-related complications. Rituximab (Rituxan) may be an effective alternative but carries the risk of immunosuppression.
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Púrpura Trombocitopénica Idiopática/etiología , Púrpura Trombocitopénica Idiopática/terapia , Corticoesteroides/uso terapéutico , Adulto , Trasplante de Células Madre Hematopoyéticas , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Factores Inmunológicos/uso terapéutico , Púrpura Trombocitopénica Idiopática/diagnóstico , Receptores de Trombopoyetina/agonistas , EsplenectomíaRESUMEN
A 47-year-old female presented with a 2-week history of painless haematuria. Urine dipstick showed moderate leucocytes. Blood and urine cultures were negative and cytology was negative for malignant cells. Flexible cystoscopy was negative for any bladder pathology. An ultrasonogram of the abdomen showed a mass in the left kidney. CT showed a mass-like lesion within the left kidney suspicious for renal carcinoma, and cavitary lesions in both lungs. Biopsy of the lung showed clusters of atypical cells suspicious for squamous cell carcinoma (SCC), and left kidney lesion showed malignant cells derived from SCC. A whole body positron emission tomography/CT showed lesions in the lungs, left kidney and skeleton. Complete clinical examination, laboratory and imaging studies did not reveal any site of primary tumour in any part of the body. Haematuria is a very unusual initial presentation of metastatic tumour to kidney.