RESUMO
Colorectal cancer is a common disease, both in Chile and worldwide. The most widely used chemotherapy schemes are based on 5-fluorouracil (5FU) as the foundational drug (FOLFOX, CapeOX). Genetic polymorphisms have emerged as potential predictive biomarkers of response to chemotherapy, but conclusive evidence is lacking. This study aimed to investigate the role of genetic variants associated with 5FU-based chemotherapy on therapeutic response, considering their interaction with oncogene mutations (KRAS, NRAS, PI3KCA, AKT1, BRAF). In a retrospective cohort of 63 patients diagnosed with metastatic colorectal cancer, a multivariate analysis revealed that liver metastases, DPYD, ABCB1, and MTHFR polymorphisms are independent indicators of poor prognosis, irrespective of oncogene mutations. BRAF wild-type status and high-risk drug-metabolism polymorphisms correlated with a poor prognosis in this Chilean cohort. Additionally, findings from the genomics of drug sensitivity (GDSC) project demonstrated that cell lines with wild-type BRAF have higher IC50 values for 5-FU compared to BRAF-mutated cell lines. In conclusion, the genetic polymorphisms DPYDrs1801265, ABCB1rs1045642, and MTHFRrs180113 may serve as useful biomarkers for predicting a poor prognosis in patients undergoing 5-fluorouracil chemotherapy, regardless of oncogene mutations.
Assuntos
Neoplasias Colorretais , Proteínas Proto-Oncogênicas B-raf , Humanos , Proteínas Proto-Oncogênicas B-raf/genética , Estudos Retrospectivos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Mutação , Fluoruracila/uso terapêutico , BiomarcadoresRESUMO
Neuroendocrine Tumors (NETs) encompass a wide variety of tumors arising from neuroendocrine cells, which produce bioactive substances. The incidence of NETs increased significantly lately, becoming one of the most common tumors of the digestive tract. Their clinical presentation is as diverse as their capacity for hormone production. Carcinoid syndrome is the most common hormonal syndrome produced by NETs and is characterized by diarrhea, flushing and cardiac valvular lesions. New research brought multiple changes in the classification of these neoplasms and a new understanding about their diagnosis and treatment, promoting a multidisciplinary approach. Somatostatin analogues, radiation, biological, and cytotoxic drugs have improved the prognosis of these patients, which entails a great challenge for healthcare providers.
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Antineoplásicos , Tumores Neuroendócrinos , Antineoplásicos/uso terapêutico , Diarreia , Humanos , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/terapia , Somatostatina/uso terapêuticoRESUMO
Neuroendocrine Tumors (NETs) encompass a wide variety of tumors arising from neuroendocrine cells, which produce bioactive substances. The incidence of NETs increased significantly lately, becoming one of the most common tumors of the digestive tract. Their clinical presentation is as diverse as their capacity for hormone production. Carcinoid syndrome is the most common hormonal syndrome produced by NETs and is characterized by diarrhea, flushing and cardiac valvular lesions. New research brought multiple changes in the classification of these neoplasms and a new understanding about their diagnosis and treatment, promoting a multidisciplinary approach. Somatostatin analogues, radiation, biological, and cytotoxic drugs have improved the prognosis of these patients, which entails a great challenge for healthcare providers.
Assuntos
Humanos , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/terapia , Antineoplásicos/uso terapêutico , Somatostatina/uso terapêutico , DiarreiaRESUMO
BACKGROUND: Regorafenib is a therapeutic alternative for patients with metastatic colorectal cancer (MCRC) resistant to conventional therapies. The reported toxicity is relevant and there is no data on Latin American patients. The objective was to evaluate the overall survival (OS), progression-free survival (PFS) and quality of life (QoL) in a prospective cohort of Latin American patients treated with an adjusted dose of regorafenib. METHODS: We prospectively recruited patients with MCRC that progressed to standard therapy. A dose escalation algorithm was used. OS, PFS, response rate and QoL were evaluated. RESULTS: We recruited 13 patients between June and November 2015. The median age was 60 years. Median OS was 8.6 months and median PFS was 2.2 months. The response rate was 8%. Grade 3-4 toxicities included grade 3 palmoplantar erythrodysesthesia in 23% and grade 3 fatigue in 12% of patients. CONCLUSION: Regorafenib treatment is effective in Latin American patients with conventional therapy resistant MCRC.
RESUMO
INTRODUCCIÓN: El cáncer de próstata (PC) es una enfermedad de alta incidencia y prevalencia (90/100.00 habitantes) y constituye la segunda causa por muerte oncológica en hombres, fenómeno que acontece en su fase metastásica (mPC). El tratamiento estándar en esta etapa corresponde a la terapia de deprivación androgénica (TDA) que produce una respuesta oncológica favorable en términos de descenso del PSA y estabilización y/o regresión de las metástasis. Ésta primera etapa (castración sensible) dura en promedio 2 a 3 años, tras lo cual ocurre una independización tumoral del estímulo androgénico, fenómeno conocido como castración-resistencia (mCRPC). En esta etapa la quimioterapia (QMT) con docetaxel prolonga la sobrevida aproximadamente 4 meses, lo cual en conjunto con otros tratamientos de segunda línea (abiraterona, enzalutamida, etc.) logra alcanzar una sobrevida media desde el diagnostico de mCRPC de 24 meses. Diversos estudios (CHAARTED y STAMPEDE) han demostrado que el inicio de docetaxel junto con TDA en pacientes con mPC castración-sensible (mCSPC) prolongan sobrevida global hasta 17 meses, especialmente si hay alto volumen de enfermedad. El objetivo del estudio es describir las características clínicas, la respuesta oncológica inicial y el perfil de efectos adversos de pacientes con mCSPC sometidos a docetaxel. MATERIALES Y MÉTODOS: Estudio retrospectivo descriptivo entre mayo 2014 a Julio 2017. Se incluyeron pacientes ng/ml (rango 10,8 - 5550) y mediana de seguimiento 6 meses (rango 3 20). Catorce pacientes tenían Gleason > 8, 18 eran M+ de los cuales 9 eran viscerales. Solo uno recibió tratamiento local previo. La mediana de inicio de QMT fue 3,1 (0 6,1) meses post inicio TDA.Dieciséis pacientes completaron docetaxel y 4 siguen en curso. No hubo suspensión de QMT por efectos adversos. Los más frecuentes fueron diarrea (8/20), neuropatía (5/20) y vómitos (2/20). La mayoría fue grado 1 y solo tres presentaron complicaciones grado 3 (diarrea, leucopenia y trombocitopenia). No hubo complicaciones grado 4 -5. Diez pacientes alcanzaron un antígeno < 2 ng/ml a las 12 semanas post tratamiento y 7 presentaron recidiva bioquímica durante el seguimiento. Uno tuvo respuesta imagenológica completa, 10 respuesta parcial, 7 estabilidad y 2 mostraron progresión. CONCLUSIONES: El uso de Docetaxel en mCSPC es seguro, presenta escasos efectos adversos (la mayoría de intensidad leve) que no motivan suspensión. El tratamiento con docetaxel exhibe una respuesta prometedora en términos de control de PSA, sin embargo se requiere mayor seguimiento de esta cohorte para evaluar impacto en sobrevida. con mCSPC con enfermedad de alto volumen (metástasis óseas extra-axiales, viscerales o Gleason 9-10) y ECOG 0-1. Los pacientes recibieron TDA y seis ciclos de Docetaxel. Se registraron datos demográficos, clínicos, histopatológicos, PSA, imagenológicos (RECIST V1.1) y toxicidad (NCI CAE 4.0) RESULTADOS: Se incluyeron 20 pacientes, mediana de edad 63 años (rango 49 75). Mediana PSA de ingreso 267,5 ng/ml (rango 10,8 - 5550) y mediana de seguimiento 6 meses (rango 3 20). Catorce pacientes tenían Gleason > 8, 18 eran M+ de los cuales 9 eran viscerales. Solo uno recibió tratamiento local previo. La mediana de inicio de QMT fue 3,1 (0 6,1) meses post inicio TDA.Dieciséis pacientes completaron docetaxel y 4 siguen en curso. No hubo suspensión de QMT por efectos adversos. Los más frecuentes fueron diarrea (8/20), neuropatía (5/20) y vómitos (2/20). La mayoría fue grado 1 y solo tres presentaron complicaciones grado 3 (diarrea, leucopenia y trombocitopenia). No hubo complicaciones grado 4 -5. Diez pacientes alcanzaron un antígeno < 2 ng/ml a las 12 semanas post tratamiento y 7 presentaron recidiva bioquímica durante el seguimiento. Uno tuvo respuesta imagenológica completa, 10 respuesta parcial, 7 estabilidad y 2 mostraron progresión. CONCLUSIONES: El uso de Docetaxel en mCSPC es seguro, presenta escasos efectos adversos (la mayoría de intensidad leve) que no motivan suspensión. El tratamiento con docetaxel exhibe una respuesta prometedora en términos de control de PSA, sin embargo se requiere mayor seguimiento de esta cohorte para evaluar impacto en sobrevida.(AU)
INTRODUCTION: Prostate cancer is a disease with high incidence and prevalence (90/100.000 habitants) and the second cause of cancer related death in men. Standard treatment in this setting is androgen-deprivation therapy (TDA), which causes decrease in PSA levels and stabilization or regression of metastatic lesions. Responses in castration sensitive phase last in average 3 years, after which tumor is described to become independent from the androgenic stimuli, reaching a castration-resistance (mCRPC) state. At this point chemotherapy with docetaxel as well as second line treatments (abiraterone, enzalutamide, among others)have shown to improve survival in 4 months with mean survival from diagnosis of mCRPC of 24 months. Studies including CHAARTED and STAMPEDE have demonstrated that early treatment with docetaxel with ADT in patients with mCSPC prolongs overall survival, especially if high volume disease exists. This study describes the clinical characteristics, initial oncologic response and side effects profile of mCSPC treated with Docetaxel plus ADT. MATERIALS AND METHODS: Descriptive Retrospective study from May 2014 to July 2017. mCSPC patients with high volume disease (extra axial bone metastasis, visceral metastasis or Gleason 9-10) and ECOG 0-1 were included. Patients received ADT and 6 cycles of Docetaxel. Demographic, clinical and histopathological characteristicswere registered, together with PSA, radiologic data (RECIST V1.1) and toxicity (NCI CAE 4.0). RESULTS: 20 patients were included, median age 63 years (49-75 range). Median initial PSA 267,5 ng/ml (10,8-5550 range), and median follow up 6 months (3-20 range). Fourteen patients had Gleason > 8, 18presented bone metastasis and 9/14 viscerametastasis. Only 1 patient received previous local treatment. Median initialtime to initiation of Docetaxel post ADT was 3,1 (0-6,1) months.Sixteen patients completed docetaxel and 4 are still receiving treatment. There was no chemotherapy suspension due side effects. Most frequent side effects were diarrhea (8/20), neuropathy (5/20) and vomiting (2/20). Most were grade 1 and three patients presented grade 3 side effects (diarrhea, leukopenia and thrombocytopenia). No grade 4-5 side effects were reported.Ten patients reached PSA< 2 ng/m after 12 weeks of treatment, and 7 had biochemical relapse during follow up. One had complete radiologic response, 10 partial response, 7 remained stable and 2 showed progression of disease. CONCLUSION: The use of docetaxel in mCSPC isassociated to few side effects and none requiredsuspension of treatment. Treatment with Docetaxel exhibits promising results in terms of decrease in PSA, however longer follow up and greater number of patients are required to report benefits in overall survival.(AU)
Assuntos
Masculino , Neoplasias da Próstata , Tratamento Farmacológico , Neoplasias de Próstata Resistentes à CastraçãoRESUMO
BACKGROUND: Multiple clinical trials have demonstrated the benefits of adjuvant 5-fluorouracil-based chemotherapy for patients with resectable colon cancer (CC), especially in stage III. AIM: To describe the clinical characteristics of a cohort of CC patients treated at a single university hospital in Chile since 2002, and to investigate if chemotherapy had an effect on survival rates. MATERIAL AND METHODS: Review of a tumor registry of the hospital. Medical records of patients with CC treated between 2002 and 2012 were reviewed. Death certificates from the National Identification Service were used to determine mortality. Overall survival was described using the Kaplan-Meier method. A multivariate Cox proportional hazard regression model was also used. RESULTS: A total of 370 patients were treated during the study period (202 in stage II and 168 in stage III). Adjuvant chemotherapy was administered to 22 and 70% of patients in stage II and III respectively. The median follow-up period was 4.6 years. The 5-year survival rate for stage II patients was 79% and there was no benefit observed with adjuvant chemotherapy. For stage III patients, the 5-year survival rate was 81% for patients who received adjuvant chemotherapy, compared to 56% for those who did not receive chemotherapy (hazard ratio (HR): 0.29; 95% confidence interval (CI): 0.15-0.56). The benefit of chemotherapy was found to persist after adjustment for other prognostic variables (HR: 0.47; 95% CI: 0.23-0.94). CONCLUSIONS: Patients with colon cancer in stage III who received adjuvant chemotherapy had a better overall survival.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias do Colo/tratamento farmacológico , Fluoruracila/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
Background: Multiple clinical trials have demonstrated the benefits of adjuvant 5-fluorouracil-based chemotherapy for patients with resectable colon cancer (CC), especially in stage III. Aim: To describe the clinical characteristics of a cohort of CC patients treated at a single university hospital in Chile since 2002, and to investigate if chemotherapy had an effect on survival rates. Material and Methods: Review of a tumor registry of the hospital. Medical records of patients with CC treated between 2002 and 2012 were reviewed. Death certificates from the National Identification Service were used to determine mortality. Overall survival was described using the Kaplan-Meier method. A multivariate Cox proportional hazard regression model was also used. Results: A total of 370 patients were treated during the study period (202 in stage II and 168 in stage III). Adjuvant chemotherapy was administered to 22 and 70% of patients in stage II and III respectively. The median follow-up period was 4.6 years. The 5-year survival rate for stage II patients was 79% and there was no benefit observed with adjuvant chemotherapy. For stage III patients, the 5-year survival rate was 81% for patients who received adjuvant chemotherapy, compared to 56% for those who did not receive chemotherapy (hazard ratio (HR): 0.29; 95% confidence interval (CI): 0.15-0.56). The benefit of chemotherapy was found to persist after adjustment for other prognostic variables (HR: 0.47; 95% CI: 0.23-0.94).Conclusions: Patients with colon cancer in stage III who received adjuvant chemotherapy had a better overall survival.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias do Colo/tratamento farmacológico , Fluoruracila/administração & dosagem , Prognóstico , Taxa de Sobrevida , Estudos Retrospectivos , Resultado do Tratamento , Quimioterapia Adjuvante , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Estadiamento de NeoplasiasRESUMO
Massive pulmonary thromboembolism has a high mortality. Early thrombolysis is the treatment of choice. We report a 79-year-old man admitted in shock. A chest angio-CAT scan showed a massive pulmonary thromboembolism. A transthoracic echocardiography showed a right cardiac dysfunction. Although the patient was in hemodynamic instability, he was subjected to thrombolysis with streptokinase, assisted with noradrenaline support and invasive mechanical ventilation. Parenteral anticoagulation was started thereafter. A second echocardiography, performed 72 hours later showed an improvement in right ventricular function. The patient had a nosocomial pneumonia that was treated. Noradrenalin and mechanical ventilation were discontinued nine and 15 days after thrombolysis. A new angio-CAT scan, 23 days after the procedure, was normal. The patient was discharged in good conditions 27 days after admission.
Assuntos
Fibrinolíticos/uso terapêutico , Embolia Pulmonar/tratamento farmacológico , Estreptoquinase/uso terapêutico , Idoso , Humanos , Masculino , Embolia Pulmonar/diagnóstico , Tomografia Computadorizada por Raios XRESUMO
Massive pulmonary thromboembolism has a high mortality. Early thrombolysis is the treatment of choice. We report a 79-year-old man admitted in shock. A chest angio-CAT scan showed a massive pulmonary thromboembolism. A transthoracic echocardiography showed a right cardiac dysfunction. Although the patient was in hemodynamic instability, he was subjected to thrombolysis with streptokinase, assisted with noradrenaline support and invasive mechanical ventilation. Parenteral anticoagulation was started thereafter. A second echocardiography, performed 72 hours later showed an improvement in right ventricular function. The patient had a nosocomial pneumonia that was treated. Noradrenalin and mechanical ventilation were discontinued nine and 15 days after thrombolysis. A new angio-CAT scan, 23 days after the procedure, was normal. The patient was discharged in good conditions 27 days after admission.
Assuntos
Idoso , Humanos , Masculino , Fibrinolíticos/uso terapêutico , Embolia Pulmonar/tratamento farmacológico , Estreptoquinase/uso terapêutico , Embolia Pulmonar/diagnóstico , Tomografia Computadorizada por Raios XRESUMO
In 2009, the World Health Organization recognized the novel H1N1 influenza A virus as a pandemic infection. Since April 2009, thousands of cases of novel H1N1 influenza A infection have been reported worldwide, and they have resulted in thousands of deaths. South American countries were affected by this infection during their winter season, and Chile presented one of the highest incidence rates. We have recently managed a liver transplant patient who presented with a severe novel H1N1 influenza A infection in the early postoperative period and required prolonged mechanical ventilation. The early suspicion of this infection during the current pandemic influenza in Chile made possible a timely treatment with oseltamivir. We decided to report this case because no other cases of liver transplant patients affected by H1N1 influenza A have been reported so far. We intend to alert clinicians about this potentially devastating viral infection in view of the current pandemic scenario, and here we review some of the recommendations for its prevention, diagnosis, therapy, and possible complications.
Assuntos
Vírus da Influenza A Subtipo H1N1/imunologia , Influenza Humana/etiologia , Transplante de Fígado/métodos , Antivirais/uso terapêutico , Primers do DNA/química , Humanos , Influenza Humana/complicações , Influenza Humana/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Oseltamivir/uso terapêutico , Reação em Cadeia da Polimerase , Período Pós-Operatório , Fatores de Tempo , Resultado do TratamentoRESUMO
Thrombotic thrombocytopenic purpura presents as a multisystemic disease with thrombocytopenia, microangiopathic hemolytic anemia, fever, neurological and renal involvement. We report a 24 years-old male presenting with purpura and a generalized seizure. His blood tests showed an hemolytic anemia, unconjungated hyperbilirubinemia, increased lactated dehydrogenase, thrombocytopenia and impairment of renal function. He was initially treated with daily plasmapheresis and steroids without improvement. Due to persistence of the disease, he was treated with two doses of intravenous vincristine in four days, with clinical and laboratory improvement. He was discharged 40 days after the last dose of vincristine, in good conditions.
Assuntos
Adulto , Humanos , Masculino , Fibrinolíticos/uso terapêutico , Púrpura Trombocitopênica Trombótica/tratamento farmacológico , Vincristina/uso terapêutico , Plasmaferese , Contagem de Plaquetas , Púrpura Trombocitopênica Trombótica/sangue , Púrpura Trombocitopênica Trombótica/diagnósticoRESUMO
Thrombotic thrombocytopenic purpura presents as a multisystemic disease with thrombocytopenia, microangiopathic hemolytic anemia, fever, neurological and renal involvement. We report a 24 years-old male presenting with purpura and a generalized seizure. His blood tests showed an hemolytic anemia, unconjugated hyperbilirubinemia, increased lactated dehydrogenase, thrombocytopenia and impairment of renal function. He was initially treated with daily plasmapheresis and steroids without improvement. Due to persistence of the disease, he was treated with two doses of intravenous vincristine in four days, with clinical and laboratory improvement. He was discharged 40 days after the last dose of vincristine, in good conditions.
Assuntos
Fibrinolíticos/uso terapêutico , Púrpura Trombocitopênica Trombótica/tratamento farmacológico , Vincristina/uso terapêutico , Adulto , Humanos , Masculino , Plasmaferese , Contagem de Plaquetas , Púrpura Trombocitopênica Trombótica/sangue , Púrpura Trombocitopênica Trombótica/diagnósticoRESUMO
Las diferentes escuelas desarrolladas en la teoria administrativa y sus modalidades permiten identificar una base para su aplicación en la administración médica, donde se requieren acciones positivas para lograr resultados