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The kidney undergoes structural and physiological changes with age, predominantly studied in glomeruli and proximal tubules. However, limited knowledge is available about the impact of aging and anti-aging interventions on distal tubules. In this study, we investigated the effects of cytochrome b5 reductase 3 (CYB5R3) overexpression and/or dietary nicotinamide riboside (NR) supplementation on distal tubule mitochondria. Initially, transcriptomic data were analyzed to evaluate key genes related with distal tubules, CYB5R3, and NAD+ metabolism, showing significant differences between males and females in adult and old mice. Subsequently, our emphasis focused on assessing how these interventions, that have demonstrated the anti-aging potential, influenced structural parameters of distal tubule mitochondria, such as morphology and mass, as well as abundance, distance, and length of mitochondria-endoplasmic reticulum contact sites, employing an electron microscopy approach. Our findings indicate that both interventions have differential effects depending on the age and sex of the mice. Aging resulted in an increase in mitochondrial size and a decrease in mitochondrial abundance in males, while a reduction in abundance, size, and mitochondrial mass was observed in old females when compared with their adult counterparts. Combining both the interventions, CYB5R3 overexpression and dietary NR supplementation mitigated age-related changes; however, these effects were mainly accounted by NR in males and by transgenesis in females. In conclusion, the influence of CYB5R3 overexpression and dietary NR supplementation on distal tubule mitochondria depends on sex, genotype, and diet. This underscores the importance of incorporating these variables in subsequent studies to comprehensively address the multifaceted aspects of aging.
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INTRODUCTION: The association between cancer and stroke is well documented and entails a worse prognosis for both pathologies. However, the prevalence of active and occult cancer among stroke patients is not sufficiently established, and neither are the predictors of cancer-associated stroke. Their knowledge is important for better identification and optimisation of the treatment of these patients. PATIENTS AND METHODS: The aim of this retrospective study is to analyse the characteristics of ischaemic stroke in patients with and without active cancer in a sample of patients admitted to a stroke unit for two years. An overall descriptive and case-control analysis is performed to assess the differences between the two groups. RESULTS: In a sample of 616 patients with ischaemic stroke, a prevalence of cancer was found to be 19.2%, which was active (prior or diagnosed after the stroke) in 7.5% of them. Active cancer was associated with the finding of lesions in several vascular territories, lower haemoglobin and haematocrit values, and higher fibrinogen and C-reactive protein values, a tendency to worse functional status and higher mortality at three months. CONCLUSIONS: A high prevalence of systemic cancer, of any type, as well as active and occult, was found among patients with ischaemic stroke. The presence of ischaemic lesions in several vascular territories and some laboratory markers could be factors to consider in attributing the stroke to cancer or looking for an occult neoplasm in some patients.
TITLE: Ictus asociado a cáncer: estudio de prevalencia y factores predictores entre pacientes con ictus isquémico.Introducción. La asociación entre cáncer e ictus está bien documentada y conlleva un peor pronóstico de ambas patologías. Sin embargo, la prevalencia de cáncer activo y cáncer oculto entre pacientes con ictus no está suficientemente establecida, ni tampoco los factores predictores al ictus asociado al cáncer. Su conocimiento es importante para una mejor identificación y optimización del tratamiento de estos pacientes. Pacientes y métodos. El objetivo de este estudio retrospectivo es analizar las características del ictus isquémico, en pacientes con y sin cáncer activo, en una muestra de pacientes ingresados durante dos años en una unidad de ictus. Se realiza un análisis descriptivo general y de casos y controles, para evaluar las diferencias entre ambos grupos. Resultados. En una muestra de 616 pacientes con ictus isquémico se encontró una prevalencia de cáncer del 19,2%, que era activo (previo o diagnosticado tras el ictus) en un 7,5%. El cáncer activo se asoció con el hallazgo de lesiones en varios territorios vasculares, valores más bajos de hemoglobina y hematocrito, y más altos de fibrinógeno y proteína C reactiva, tendencia a peor situación funcional y mayor mortalidad a los tres meses. Conclusiones. Se encontró una alta prevalencia de cáncer sistémico, de cualquier tipo, y también activo y oculto, entre pacientes con ictus isquémico. La presencia de lesiones isquémicas en varios territorios vasculares y algunos marcadores de laboratorio podrían ser factores que habría que considerar para atribuir el ictus al cáncer o buscar una neoplasia oculta en algunos pacientes.
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Isquemia Encefálica , AVC Isquêmico , Neoplasias , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/complicações , Isquemia Encefálica/complicações , Estudos Retrospectivos , Prevalência , Neoplasias/complicaçõesRESUMO
Introducción: La asociación entre cáncer e ictus está bien documentada y conlleva un peor pronóstico de ambas patologías. Sin embargo, la prevalencia de cáncer activo y cáncer oculto entre pacientes con ictus no está suficientemente establecida, ni tampoco los factores predictores al ictus asociado al cáncer. Su conocimiento es importante para una mejor identificación y optimización del tratamiento de estos pacientes. Pacientes y métodos: El objetivo de este estudio retrospectivo es analizar las características del ictus isquémico, en pacientes con y sin cáncer activo, en una muestra de pacientes ingresados durante dos años en una unidad de ictus. Se realiza un análisis descriptivo general y de casos y controles, para evaluar las diferencias entre ambos grupos. Resultados: En una muestra de 616 pacientes con ictus isquémico se encontró una prevalencia de cáncer del 19,2%, que era activo (previo o diagnosticado tras el ictus) en un 7,5%. El cáncer activo se asoció con el hallazgo de lesiones en varios territorios vasculares, valores más bajos de hemoglobina y hematocrito, y más altos de fibrinógeno y proteína C reactiva, tendencia a peor situación funcional y mayor mortalidad a los tres meses. Conclusiones: Se encontró una alta prevalencia de cáncer sistémico, de cualquier tipo, y también activo y oculto, entre pacientes con ictus isquémico. La presencia de lesiones isquémicas en varios territorios vasculares y algunos marcadores de laboratorio podrían ser factores que habría que considerar para atribuir el ictus al cáncer o buscar una neoplasia oculta en algunos pacientes.(AU)
Introduction: The association between cancer and stroke is well documented and entails a worse prognosis for both pathologies. However, the prevalence of active and occult cancer among stroke patients is not sufficiently established, and neither are the predictors of cancer-associated stroke. Their knowledge is important for better identification and optimisation of the treatment of these patients. Patients and methods: The aim of this retrospective study is to analyse the characteristics of ischaemic stroke in patients with and without active cancer in a sample of patients admitted to a stroke unit for two years. An overall descriptive and case-control analysis is performed to assess the differences between the two groups. Results: In a sample of 616 patients with ischaemic stroke, a prevalence of cancer was found to be 19.2%, which was active (prior or diagnosed after the stroke) in 7.5% of them. Active cancer was associated with the finding of lesions in several vascular territories, lower haemoglobin and haematocrit values, and higher fibrinogen and C-reactive protein values, a tendency to worse functional status and higher mortality at three months. Conclusions: A high prevalence of systemic cancer, of any type, as well as active and occult, was found among patients with ischaemic stroke. The presence of ischaemic lesions in several vascular territories and some laboratory markers could be factors to consider in attributing the stroke to cancer or looking for an occult neoplasm in some patients.(AU)
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Humanos , Masculino , Feminino , Acidente Vascular Cerebral , Síndrome da Deleção Distal 11q de Jacobsen , Neoplasias , Doenças Vasculares , Estudos Transversais , Estudos RetrospectivosRESUMO
Venous thromboembolic disease (VTED) is a common and clinically important complication in patients with cancer, contributing to its mortality and morbidity. Direct oral anticoagulant agents (DOACs), including direct thrombin inhibitors and direct factor Xa inhibitors, are as effective as vitamin K antagonists for the treatment of VTED and are associated with less frequent and severe bleeding. They have advantages over low-molecular-weight heparin, but comparative long-term efficacy and safety data are lacking for these compounds. Recent randomized clinical trials suggest a role for DOACs in the treatment of VTED in patients with cancer. This review will discuss the existing evidence and future perspectives on the role of DOACs in the treatment of VTE based on the current evidence about their overall efficacy and safety and the limited information in patients with cancer; in addition, we will briefly review their pharmacokinetic properties with special reference to potential interactions (AU)
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Anticoagulantes/uso terapêutico , Neoplasias/complicações , Tromboembolia/etiologia , Tromboembolia/prevenção & controle , Guias de Prática Clínica como AssuntoRESUMO
Background and rationale Thromboembolic complications are a serious, preventable and common event in cancer patients that contributes to increasing morbidity and mortality. Despite increasing knowledge on cancer-associated thrombosis (CAT), there are still several aspects of diagnosis, clinical management, treatment and prognosis with uncertainties that are under-represented in randomized clinical trials. For this reason, the Spanish Society of Medical Oncology (SEOM) launched in June 2018 a registry of CAT. Methods/design TESEO is an ongoing prospective, non-interventional, multicentric study in consecutive cancer patients with newly diagnosed of thromboembolic event (TEE). Eligibility criteria include being > 18 years with a histologically confirmed diagnosis of cancer and a symptomatic or incidental TEE confirmed with an imaging technique in the previous month or any time after the cancer diagnosis and signing of informed consent. The study consists of two types of integrated but independent prospective registries. Regular CAT sub-registry includes information on patients cancer´s characteristics, anticoagulant treatment provided and outcome data. Special CAT sub-registry includes variables related to special situations of CAT that comprise patients with severe kidney failure, thrombocytopenia, high risk of bleeding related to the cancer or with coexistence of bleeding and patients who receive new treatments such a targeted therapy, antiangiogenics agents and immunotherapy. The registry considers the status of the cancer and the time to assess how the prognosis is changed based on when the thrombus occurs. Some outcomes such as rethrombosis, major bleeding, tumor progression and survival will be valued in various time intervals including 1, 3, 6 and 12 months after the even in the first year; and then every 6 months until the patients death. Results After 18 months and with 35 centers and researchers, the registry has 1128 patients (AU)
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Humanos , Neoplasias/complicações , Trombose/etiologia , Estudos Prospectivos , Anticoagulantes/uso terapêutico , Inibidores da Angiogênese/uso terapêutico , Antineoplásicos Imunológicos , Neoplasias/terapia , Sociedades Médicas , Espanha , Trombose/tratamento farmacológico , Trombose/prevenção & controle , PrognósticoRESUMO
Purpose Outcomes for patients with metastatic colorectal cancer (mCRC) have been improved by the identification of biomarkers predictive and prognostic of clinical outcome. The present retrospective analysis was undertaken to assess the utility of key biomarkers and clinical parameters in predicting outcomes in Spanish patients with mCRC. Methods We retrospectively analyzed tumor samples from a series of patients aged > 18 years with mCRC who were treated at the Hospital General Universitario Gregorio Marañón Spain. Real-time polymerase chain reaction was used to detect KRAS, NRAS, BRAF, and PIK3CA mutations. The key outcome of interest was overall survival (OS). Survival curves were estimated using the KaplanMeier method and stratified by the variables of greatest clinical interest. Differences were tested using the log-rank test. Results Median OS in the overall population was 24.4 months. Triple WT patients (WT KRAS, NRAS, and BRAF) and quadruple WT patients (WT KRAS, NRAS, BRAF, and PIK3CA) had significantly better OS than those who did not have triple or quadruple WT tumors. OS was significantly better in patients with left- vs. right-sided tumors, patients with resected primary tumors and metastases vs. those without resection, and patients with isolated hepatic and isolated pulmonary metastases. Conclusions This retrospective, observational study has confirmed the prognostic value of the location and resection status of the primary tumor and metastases in Spanish patients with mCRC. Triple WT status, in particular, was prognostic in this patient population, with PIK3CA adding to the prognostic value in the quadruple WT population (AU)
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Humanos , Marcadores Genéticos , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Metástase Neoplásica/genética , Metástase Neoplásica/patologia , Estudos Retrospectivos , Fatores de Tempo , Estimativa de Kaplan-Meier , Biomarcadores Tumorais , PrognósticoRESUMO
BACKGROUND AND RATIONALE: Thromboembolic complications are a serious, preventable and common event in cancer patients that contributes to increasing morbidity and mortality. Despite increasing knowledge on cancer-associated thrombosis (CAT), there are still several aspects of diagnosis, clinical management, treatment and prognosis with uncertainties that are under-represented in randomized clinical trials. For this reason, the Spanish Society of Medical Oncology (SEOM) launched in June 2018 a registry of CAT. METHODS/DESIGN: TESEO is an ongoing prospective, non-interventional, multicentric study in consecutive cancer patients with newly diagnosed of thromboembolic event (TEE). Eligibility criteria include being > 18 years with a histologically confirmed diagnosis of cancer and a symptomatic or incidental TEE confirmed with an imaging technique in the previous month or any time after the cancer diagnosis and signing of informed consent. The study consists of two types of integrated but independent prospective registries. Regular CAT sub-registry includes information on patient's cancer´s characteristics, anticoagulant treatment provided and outcome data. Special CAT sub-registry includes variables related to special situations of CAT that comprise patients with severe kidney failure, thrombocytopenia, high risk of bleeding related to the cancer or with coexistence of bleeding and patients who receive new treatments such a targeted therapy, antiangiogenics agents and immunotherapy. The registry considers the status of the cancer and the time to assess how the prognosis is changed based on when the thrombus occurs. Some outcomes such as rethrombosis, major bleeding, tumor progression and survival will be valued in various time intervals including 1, 3, 6 and 12 months after the even in the first year; and then every 6 months until the patient's death. RESULTS: After 18 months and with 35 centers and researchers, the registry has 1128 patients. CONCLUSION: TESEO registry will provide clinical real-world evidence for prevention, treatment and complications of CAT in different scenarios that are under-represented in randomized clinical trials.
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Neoplasias/complicações , Sistema de Registros/estatística & dados numéricos , Tromboembolia/epidemiologia , Inibidores da Angiogênese/uso terapêutico , Anticoagulantes/uso terapêutico , Progressão da Doença , Hemorragia/epidemiologia , Humanos , Imunoterapia , Oncologia , Terapia de Alvo Molecular , Neoplasias/terapia , Prognóstico , Recidiva , Insuficiência Renal/epidemiologia , Sociedades Médicas , Espanha/epidemiologia , Trombocitopenia/epidemiologia , Tromboembolia/tratamento farmacológico , Tromboembolia/etiologia , Tromboembolia/prevenção & controle , Resultado do Tratamento , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologiaRESUMO
PURPOSE: Outcomes for patients with metastatic colorectal cancer (mCRC) have been improved by the identification of biomarkers predictive and prognostic of clinical outcome. The present retrospective analysis was undertaken to assess the utility of key biomarkers and clinical parameters in predicting outcomes in Spanish patients with mCRC. METHODS: We retrospectively analyzed tumor samples from a series of patients aged > 18 years with mCRC who were treated at the Hospital General Universitario Gregorio Marañón Spain. Real-time polymerase chain reaction was used to detect KRAS, NRAS, BRAF, and PIK3CA mutations. The key outcome of interest was overall survival (OS). Survival curves were estimated using the Kaplan-Meier method and stratified by the variables of greatest clinical interest. Differences were tested using the log-rank test. RESULTS: Median OS in the overall population was 24.4 months. Triple WT patients (WT KRAS, NRAS, and BRAF) and quadruple WT patients (WT KRAS, NRAS, BRAF, and PIK3CA) had significantly better OS than those who did not have triple or quadruple WT tumors. OS was significantly better in patients with left- vs. right-sided tumors, patients with resected primary tumors and metastases vs. those without resection, and patients with isolated hepatic and isolated pulmonary metastases. CONCLUSIONS: This retrospective, observational study has confirmed the prognostic value of the location and resection status of the primary tumor and metastases in Spanish patients with mCRC. Triple WT status, in particular, was prognostic in this patient population, with PIK3CA adding to the prognostic value in the quadruple WT population.
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Classe I de Fosfatidilinositol 3-Quinases/genética , Neoplasias Colorretais/genética , GTP Fosfo-Hidrolases/genética , Genes ras , Proteínas de Membrana/genética , Mutação/genética , Proteínas Proto-Oncogênicas B-raf/genética , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Espanha , Fatores de TempoRESUMO
Venous thromboembolic disease (VTED) is a common and clinically important complication in patients with cancer, contributing to its mortality and morbidity. Direct oral anticoagulant agents (DOACs), including direct thrombin inhibitors and direct factor Xa inhibitors, are as effective as vitamin K antagonists for the treatment of VTED and are associated with less frequent and severe bleeding. They have advantages over low-molecular-weight heparin, but comparative long-term efficacy and safety data are lacking for these compounds. Recent randomized clinical trials suggest a role for DOACs in the treatment of VTED in patients with cancer. This review will discuss the existing evidence and future perspectives on the role of DOACs in the treatment of VTE based on the current evidence about their overall efficacy and safety and the limited information in patients with cancer; in addition, we will briefly review their pharmacokinetic properties with special reference to potential interactions.
Assuntos
Inibidores do Fator Xa/uso terapêutico , Neoplasias/complicações , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/prevenção & controle , Humanos , Guias de Prática Clínica como Assunto , Tromboembolia Venosa/etiologiaRESUMO
BACKGROUND: There are conflicting data regarding the role of KRAS mutation on the risk of venous thromboembolism (VTE) in colorectal cancer (CRC) patients. Moreover, the role of other biomarkers such as NRAS or BRAF has not been studied. PURPOSE: To analyze the incidence of VTE in a cohort of patients with CRC based on KRAS, NRAS, and BRAF status. METHODS: We performed a retrospective review of patients with unresectable locally advanced and metastatic CRC (mCRC) and known KRAS/NRAS/BRAF status, attended in the Medical Oncology Department of the Hospital General Universitario Gregorio Marañón (Madrid, Spain). The primary outcome was VTE defined as any venous thromboembolic event that occurred either 6 months before or at any time after the diagnosis of CRC. The biomarker status (KRAS, NRAS, and BRAF) and other predictors of thrombosis were collected. RESULTS: One hundred and ninety-four patients were identified and included in the analysis. Forty-one patients (21.1%) experienced VTE. The incidence was 19.1% in RAS-mutated patients, 28.6% in BRAF-mutated patients and 21% in triple wild-type patients (p = NS). In multivariate analysis, ECOG ≥ 2 was the only independent predictor of VTE (OR 8.73; CI 95% 1.32-57.82; p = 0.025). CONCLUSIONS: In our study, biomarkers have not been associated with an increased risk of VTE in CRC patients. A high incidence of VTE in BRAF-mutated patients has been observed and should be explored in further studies.
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Neoplasias Colorretais/genética , GTP Fosfo-Hidrolases/genética , Proteínas de Membrana/genética , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Tromboembolia Venosa/epidemiologia , Idoso , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tromboembolia Venosa/etiologiaRESUMO
In 2011, the Spanish Society of Medical Oncology (SEOM) first published a clinical guideline of venous thromboembolism (VTE) and cancer. This guideline was updated in 2014, and since then, multiple studies and clinical trials have changed the landscape of the treatment and prophylaxis of VTE in cancer patients. To incorporate the most recent evidence, including data from direct oral anticoagulants (DOACs) randomized clinical trials, SEOM presents a new update of the guideline.
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Ensaios Clínicos como Assunto/normas , Neoplasias/terapia , Guias de Prática Clínica como Assunto/normas , Tromboembolia Venosa/terapia , Humanos , Sociedades MédicasAssuntos
Oncologia , Neoplasias/complicações , Sistema de Registros/estatística & dados numéricos , Sociedades Médicas , Trombose Venosa/etiologia , Antineoplásicos/efeitos adversos , Cisplatino/efeitos adversos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Espanha , Trombose Venosa/tratamento farmacológicoRESUMO
OBJECTIVE: To analyze the relationship between therapeutic (weight-adjusted) dose of bemiparin and anti-Xa activity in patients with venous thromboembolism (VTE) and cancer in comparison with a cohort of patients with VTE without cancer, and its relationship with outcomes. MATERIALS AND METHODS: This is a prospective cohort study that comprised a cohort of patients with cancer-associated VTE and a cohort of non-cancer patients with VTE, all of them treated with bemiparin. The ethics committee approved the study and informed consent was obtained from the patients. RESULTS: One hundred patients were included (52 with cancer and 48 without cancer), with a median follow-up of 9.8 months. Mean anti-Xa activity was 0.89 (± 0.33) UI/mL in oncological patients and 0.83 (± 0.30) UI/mL in non-cancer patients (mean difference - 0.05 95% CI - 0.18; 0.06). A multiple linear regression model showed that anti-Xa peak was associated with the dose/kg independently of possible confounding variables (presence of cancer, age, sex and eGFR-estimated Glomerular Filtration Rate), in a way that for every 1 UI of dose/kg increase, the anti-Xa peak activity increased 0.006 UI/mL (95% CI 0.003; 0.009) (p < 0.001). The predictive capacity of anti-Xa peak in the oncology cohort showed an area under the ROC curve of 0.46 (95% CI 0.24-0.68), 0.70 (95% CI 0.49-0.91) and 0.74 (95% CI 0.44-0.94) for death, first bleeding and recurrence of VTE, respectively, and none was statistically significant. CONCLUSION: In patients with venous thromboembolism treated with bemiparin, anti-Xa levels were not influenced by the presence of cancer.
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Anticoagulantes/uso terapêutico , Inibidores do Fator Xa/sangue , Heparina de Baixo Peso Molecular/uso terapêutico , Neoplasias/complicações , Tromboembolia Venosa/sangue , Idoso , Anticoagulantes/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Heparina de Baixo Peso Molecular/efeitos adversos , Humanos , Modelos Lineares , Masculino , Neoplasias/sangue , Estudos Prospectivos , Insuficiência Renal/diagnóstico , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/etiologiaRESUMO
Endorheic or closed drainage basins in arid and semi-arid regions are vulnerable to pollution. Nonetheless, in the freshwater-saltwater interface of endorheic saline lakes, oxidation-reduction (redox) reactions can attenuate pollutants such as nitrate (NO3-). This study traces the ways of nitrogen (N) removal in the Pétrola lake-aquifer system (central Spain), an endorheic basin contaminated with NO3- (up to 99.2mg/L in groundwater). This basin was declared vulnerable to NO3- pollution in 1998 due to the high anthropogenic pressures (mainly agriculture and wastewaters). Hydrochemical, multi-isotopic (δ18ONO3, δ15NNO3, δ13CDIC, δ18OH2O, and δ2HH2O) and geophysical techniques (electrical resistivity tomography) were applied to identify the main redox processes at the freshwater-saltwater interface. The results showed that the geometry of this interface is influenced by land use, causing spatial variability of nitrogen biogeochemical processes over the basin. In the underlying aquifer, NO3- showed an average concentration of 38.5mg/L (n=73) and was mainly derived from agricultural inputs. Natural attenuation of NO3- was observed in dryland farming areas (up to 72%) and in irrigation areas (up to 66%). In the Pétrola Lake, mineralization and organic matter degradation in lake sediment play an important role in NO3- reduction. Our findings are a major step forward in understanding freshwater-saltwater interfaces as reactive zones for NO3- attenuation. We further emphasize the importance of including a land use perspective when studying water quality-environmental relationships in hydrogeological systems dominated by density-driven circulation.
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The association between venous thromboembolism (VTE) and cancer has been recognized for more than 100 years. Numerous studies have been performed to investigate strategies to decrease VTE incidence and to establish whether treating VTE impacts cancer progression and overall survival. Accordingly, it is important to understand the role of the hemostatic system in tumorigenesis and progression, as there is abundant evidence associating it with cell survival and proliferation, tumor angiogenesis, invasion, and dissemination, and metastasis formation. In attempts to further the scientific evidence, several studies examine survival benefits in cancer patients treated with anticoagulant therapy, specifically treatment with vitamin K antagonists, unfractionated heparin, and low-molecular-weight heparin. Several studies and meta-analyses have been conducted with a special focus on brain tumors. However, no definitive conclusions have been obtained, and more well-designed clinical trials are needed.
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Anticoagulantes/uso terapêutico , Heparina/uso terapêutico , Neoplasias/tratamento farmacológico , Ensaios Clínicos como Assunto , Heparina/farmacologia , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Neoplasias/mortalidade , Tromboembolia Venosa/prevenção & controle , Vitamina K/antagonistas & inibidoresRESUMO
The treatment of choice of metastatic PADC is systemic chemotherapy. In the last decade, there have been significant advances in this area. New combination poli-chemotherapy schemes have shown a significant increase in overall survival and progression-free survival without impairing quality of life. In addition, the value of second-line chemotherapy treatment has consolidated and a new concept called "therapeutic sequencing" has also emerged. The aim of this article is to review the different therapeutic options in metastatic PDAC based on patient's characteristics.
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Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Ductal Pancreático/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Qualidade de Vida , Adenocarcinoma/secundário , Carcinoma Ductal Pancreático/secundário , Humanos , Neoplasias Pancreáticas/patologia , Prognóstico , Neoplasias PancreáticasRESUMO
INTRODUCTION: Decision-making in cancer-related venous thromboembolism (VTE) is often founded on scant lines of evidence and weak recommendations. The aim of this work is to evaluate the percentage of agreement surrounding a series of statements about complex, clinically relevant, and highly uncertain aspects to formulate explicit action guidelines. MATERIALS AND METHODS: Opinions were based on a structured questionnaire with appropriate scores and were agreed upon using a Delphi method. Questions were selected based on a list of recommendations with low evidence from the Spanish Society of Oncology Clinical Guideline for Thrombosis. The questionnaire was completed in two iterations by a multidisciplinary panel of experts in thrombosis. RESULTS: Of the 123 statements analyzed, the panel concurred on 22 (17%) and another 81 (65%) were agreed on by qualified majority, including important aspects of long-term and prolonged anticoagulation, major bleeding and rethrombosis management, treatment in special situations, catheter-related thrombosis and thromboprophylaxis. Among them, the panelists agreed the incidental events should be equated to symptomatic ones, long-term and extended use of full-dose low-molecular weight heparin, and concluded that the Khorana score is not sensitive enough to uphold an effective thromboprophylaxis strategy. CONCLUSION: Though the level of consensus varied depending on the scenario presented, overall, the iterative process achieved broad agreement as to the general treatment principles of cancer-associated VTE. Clinical validation of these statements in genuine practice conditions would be useful.
Assuntos
Anticoagulantes/uso terapêutico , Neoplasias/complicações , Guias de Prática Clínica como Assunto/normas , Trombose/prevenção & controle , Medicina Baseada em Evidências , Humanos , Oncologia , Prognóstico , Medição de Risco , Trombose/etiologiaRESUMO
Cancer is often complicated by venous thromboembolism (VTE), a common and potentially fatal complication associated with poor prognosis in these patients. An increased incidence of VTE is being observed due to the advanced age of cancer patients, the thrombogenic effect of novel drugs and advances in the diagnosis of related complications. In this review, we look at five different risk groups of cancer patients with an increased probability of developing VTE, including hospitalized patients undergoing chemotherapy, patients undergoing a surgical procedure, ambulatory patients undergoing chemotherapy, patients with a central venous access and patients receiving antiangiogenic drugs or anticoagulant therapy due to previous chronic diseases. The aim of this review is to summarize the most important clinical evidence reported to date on the suitability of primary thromboprophylaxis to cancer patients. Recommendations have drawn up for each group based on current evidence and guidelines to facilitate decision-making in clinical practice (AU)
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Humanos , Masculino , Feminino , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/prevenção & controle , Trombose/tratamento farmacológico , Trombose/prevenção & controle , Inibidores da Angiogênese/uso terapêutico , Cateterismo Venoso Central/instrumentação , Cateterismo Venoso Central/métodos , Neoplasias/tratamento farmacológico , Cateterismo Venoso Central/normas , Cateterismo Venoso Central , Antibioticoprofilaxia/métodos , Fatores de Risco , Mieloma Múltiplo/tratamento farmacológicoRESUMO
Cancer is often complicated by venous thromboembolism (VTE), a common and potentially fatal complication associated with poor prognosis in these patients. An increased incidence of VTE is being observed due to the advanced age of cancer patients, the thrombogenic effect of novel drugs and advances in the diagnosis of related complications. In this review, we look at five different risk groups of cancer patients with an increased probability of developing VTE, including hospitalized patients undergoing chemotherapy, patients undergoing a surgical procedure, ambulatory patients undergoing chemotherapy, patients with a central venous access and patients receiving antiangiogenic drugs or anticoagulant therapy due to previous chronic diseases. The aim of this review is to summarize the most important clinical evidence reported to date on the suitability of primary thromboprophylaxis to cancer patients. Recommendations have drawn up for each group based on current evidence and guidelines to facilitate decision-making in clinical practice.
Assuntos
Anticoagulantes/uso terapêutico , Neoplasias/complicações , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle , Humanos , PrognósticoRESUMO
OBJECTIVE: To analyse the evolution of a multidisciplinary heredofamilial cancer unit (HFCU) in a university hospital. METHODS: This was a retrospective analysis of the activity of our HFCU in its first 5 years of existence. RESULTS: Between July 2010 and July 2015, 1,518 patients from 1,318 families attended our HFCU. Genetic testing was offered to 862 patients. Of those, 833 (96.6%) accepted testing, with available results for 636 (76.4%). Pathogenic mutations in BRCA1 and BRCA2 were found in 175 patients. Lynch syndrome and adenomatous polyposis were the most frequent syndromes diagnosed (151/175, 86.3%) among 17 different syndromes studied. Of the 404 patients without a previous genetic diagnosis in the family, 62 (15.3%) were found to have mutations in disease-causing genes. Prophylactic surgery and follow-up (33.7%) or follow-up only (66.3%) was proposed for mutation carriers according to international guidelines and patients' preferences. CONCLUSION: We have a high mutation detection rate, genetic test acceptance, and compliance with risk reduction strategies. However, there is room for improvement, especially in genetic testing timing, considering that an increase in the indications for genetic testing is expected.