RESUMO
BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy increases progression-free and overall survival in patients with peritoneal carcinomatosis of appendicular or colorectal origin. The morbidity associated with this procedure is significant (30-52%). This modality is also routinely used in other peritoneal diseases with improvement of outcome. The aim of this study was to analyze the morbidity and mortality associated with this procedure. MATERIAL & METHODS: Thirteen patients had cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in a period from May 2011 to March 2013 and were followed up prospectively. Demographic, pathologic, and surgical variables were recorded. The Clavien-Dindo classification was used to assess surgical complications. The main outcome variable was 30-day morbidity and mortality. Descriptive statics were used. RESULTS: The mean patient age was 52.4 ± 11.1 years. The most common diagnosis was epithelial ovarian cancer (46.2%). Most patients had an adequate preoperative functional status (77% with ECOG 0). Mean hospital stay was 13.5 ± 11.2 days and 2.7 ± 4.2 days in the intensive care unit. Major morbidity (Clavien-Dindo III or IV) observed in this series was 23%, with 0% mortality. CONCLUSION: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy is a feasible option with acceptable morbidity and mortality for selected patients with peritoneal carcinomatosis in Mexico.
Assuntos
Procedimentos Cirúrgicos de Citorredução/métodos , Hipertermia Induzida/métodos , Neoplasias Peritoneais/terapia , Complicações Pós-Operatórias/epidemiologia , Adulto , Carcinoma Epitelial do Ovário , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Feminino , Humanos , Hipertermia Induzida/efeitos adversos , Tempo de Internação , Masculino , México , Pessoa de Meia-Idade , Neoplasias Epiteliais e Glandulares/terapia , Neoplasias Ovarianas/terapia , Neoplasias Peritoneais/patologia , Estudos Prospectivos , Centros de Atenção TerciáriaRESUMO
BACKGROUND: Calcitriol antiproliferative effects include inhibition of the oncogenic ether-à-go-go-1 potassium channel (Eag1) expression, which is necessary for cell cycle progression and tumorigenesis. Astemizole, a new promising antineoplastic drug, targets Eag1 by blocking ion currents. Herein, we characterized the interaction between calcitriol and astemizole as well as their conjoint antiproliferative action in SUM-229PE, T-47D and primary tumor-derived breast cancer cells. METHODOLOGY/PRINCIPAL FINDINGS: Molecular markers were studied by immunocytochemistry, Western blot and real time PCR. Inhibitory concentrations were determined by dose-response curves and metabolic activity assays. At clinically achievable drug concentrations, synergistic antiproliferative interaction was observed between calcitriol and astemizole, as calculated by combination index analysis (CI <1). Astemizole significantly enhanced calcitriol's growth-inhibitory effects (3-11 folds, P<0.01). Mean IC(20) values were 1.82 ± 2.41 nM and 1.62 ± 0.75 µM; for calcitriol (in estrogen receptor negative cells) and astemizole, respectively. Real time PCR showed that both drugs alone downregulated, while simultaneous treatment further reduced Ki-67 and Eag1 gene expression (P<0.05). Astemizole inhibited basal and calcitriol-induced CYP24A1 and CYP3A4 mRNA expression (cytochromes involved in calcitriol and astemizole degradation) in breast and hepatoma cancer cells, respectively, while upregulated vitamin D receptor (VDR) expression. CONCLUSIONS/SIGNIFICANCE: Astemizole synergized calcitriol antiproliferative effects by downregulating CYP24A1, upregulating VDR and targeting Eag1. This study provides insight into the molecular mechanisms involved in astemizole-calcitriol combined antineoplastic effect, offering scientific support to test both compounds in combination in further preclinical and clinical studies of neoplasms expressing VDR and Eag1. VDR-negative tumors might also be sensitized to calcitriol antineoplastic effects by the use of astemizole. Herein we suggest a novel combined adjuvant therapy for the management of VDR/Eag1-expressing breast cancer tumors. Since astemizole improves calcitriol bioavailability and activity, decreased calcitriol dosing is advised for conjoint administration.
Assuntos
Astemizol/farmacologia , Calcitriol/farmacologia , Proliferação de Células/efeitos dos fármacos , Receptores de Calcitriol/metabolismo , Esteroide Hidroxilases/metabolismo , Antineoplásicos/farmacologia , Western Blotting , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Agonistas dos Canais de Cálcio/farmacologia , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Sinergismo Farmacológico , Canais de Potássio Éter-A-Go-Go/genética , Canais de Potássio Éter-A-Go-Go/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Imuno-Histoquímica , Antígeno Ki-67/genética , Antígeno Ki-67/metabolismo , Modelos Genéticos , Receptores de Calcitriol/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Esteroide Hidroxilases/genética , Células Tumorais Cultivadas , Regulação para Cima/efeitos dos fármacos , Vitamina D3 24-HidroxilaseRESUMO
Hypertermic intraperitoneal chemotherapy is a treatment option after cytorreduction of certain types of malignancies with peritoneal spread. Blistering of the Glisson's capsule has not been previously reported as a consequence of this treatment modality. Patient do not experiment any associated morbidity.
Assuntos
Vesícula/etiologia , Vesícula/patologia , Tecido Conjuntivo/patologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Hipertermia Induzida/efeitos adversos , Fígado/patologia , Terapia Combinada , Tratamento Farmacológico/métodos , Feminino , Humanos , Hipertermia Induzida/métodos , Infusões Parenterais , Pessoa de Meia-Idade , Neoplasias Císticas, Mucinosas e Serosas/secundário , Neoplasias Císticas, Mucinosas e Serosas/terapia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/terapia , Resultado do TratamentoRESUMO
Introducción. Se ha sugerido que el tamaño de los tumores foliculares y su tiempo de evolución podrían ser de utilidad para predecir el diagnóstico de malignidad. Objetivo. El objetivo del presente estudio fue evaluar el comportamiento clínico de 35 ade4nomas foliculares = 5 cm tratados mediante cirugía para enfermedad benigna en un periodo de 23 años. Sede. Instituto Nacional de la Nutrición. México. Pacientes y métodos. Del total de pacientes llevados a cirugía por enfermedad benigna, en nuestro hospital, se seleccionaron aquellos con tumores iguales o superiores a 5 cm. Se revisaron sus características general, estudio histológico y su evolución a largo plazo en busca de recidiva o metástasis. Se empleo prueba t de Student para el análisis estadístico. Resultados. Se encontraron 30 mujres y 5 hombres con una edad promedio de 41.6 ñ 14.3 años. Treinta y dos tumores fueron sólidos y 3 mostraron un patrón mixto. El diámetro promedio de las lesiones fue de 6.8 ñ 1.4 cm. Se realizó lobectomía unilateral en 27 pacientes y tiroidectomía subtotal en 8. Se estableció el diagnóstico de adenoma folicular en todos los pacientes, revisando en promedio 6 ñ 3 laminillas. En un seguimiento promedio de 15.3 ñ 7.04 años, no hubo evidencia de recurrencia local o metástasis a distancia en ninguno de los pacientes. Se comparó el tiempo de evolución de los pacientes con el de un grupo de 25 enfermos con carcinoma folicular sin encontrar diferencias significativas. Conclusión. Ni el tamaño del tumor ni su tiempo de evolución son marcadores útiles para predecir malignidad