RESUMEN
INTRODUCTION AND OBJECTIVES: We investigated the anatomical localization, biomechanical properties, and molecular phenotype of myocardial collagen tissue in 40 patients with severe aortic stenosis with preserved ejection fraction and symptoms of heart failure. METHODS: Two transmural biopsies were taken from the left ventricular free wall. Mysial and nonmysial regions of the collagen network were analyzed. Myocardial collagen volume fraction (CVF) was measured by picrosirius red staining. Young's elastic modulus (YEM) was measured by atomic force microscopy in decellularized slices to assess stiffness. Collagen types I and III were measured as CIVF and CIIIVF, respectively, by confocal microscopy in areas with YEM evaluation. RESULTS: Compared with controls, patients exhibited increased mysial and nonmysial CVF and nonmysial:mysial CVF ratio (P < .05). In patients, nonmysial CVF (r = 0.330; P = .046) and the nonmysial:mysial CVF ratio (r = 0.419; P = .012) were directly correlated with the ratio of maximal early transmitral flow velocity in diastole to early mitral annulus velocity in diastole. Both the CIVF:CIIIVF ratio and YEM were increased (P ≤ .001) in nonmysial regions compared with mysial regions in patients, with a direct correlation (r = 0.895; P < .001) between them. CONCLUSIONS: These findings suggest that, in patients with severe aortic stenosis with preserved ejection fraction and symptoms of heart failure, diastolic dysfunction is associated with increased nonmysial deposition of collagen, predominantly type I, resulting in increased extracellular matrix stiffness. Therefore, the characteristics of collagen tissue may contribute to diastolic dysfunction in these patients.
Asunto(s)
Estenosis de la Válvula Aórtica/fisiopatología , Colágeno Tipo III/metabolismo , Colágeno Tipo I/metabolismo , Diástole , Insuficiencia Cardíaca/fisiopatología , Miocardio/metabolismo , Volumen Sistólico , Anciano , Anciano de 80 o más Años , Estenosis de la Válvula Aórtica/metabolismo , Fenómenos Biomecánicos , Velocidad del Flujo Sanguíneo , Módulo de Elasticidad/fisiología , Matriz Extracelular , Femenino , Insuficiencia Cardíaca/metabolismo , Humanos , Inmunohistoquímica , Masculino , Microscopía de Fuerza Atómica , Microscopía Confocal , Persona de Mediana Edad , Miocardio/patología , Péptido Natriurético Encefálico/metabolismo , Fragmentos de Péptidos/metabolismo , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Gemcitabine and erlotinib have shown a survival benefit in the first-line setting in metastatic pancreatic cancer (mPC). The aim of this study was to assess whether combining capecitabine (C) with gemcitabine + erlotinib (GE) was safe and effective versus GE in patients with mPC. PATIENTS AND METHODS: Previously untreated mPC patients were randomised to receive G (1000 mg/m2, days 1, 8, 15) + E (100 mg/day, days 1-28) + C (1660 mg/m2, days 1-21) or GE, q4 weeks, until progression or unacceptable toxicity. Primary end-point: progression-free survival (PFS); secondary end-points: overall survival (OS), response rate, relationship of rash with PFS/OS and safety. RESULTS: 120 patients were randomised, median age 63 years, ECOG status 0/1/2 33%/58%/8%; median follow-up 16.5 months. Median PFS in the gemcitabine-erlotinib-capecitabine (GEC) and GE arms was 4.3 and 3.8 months, respectively (hazard ratio [HR]: 0.88, 95% confidence interval [CI]: 0.58-1.31; p = 0.52). Median OS in the GEC and GE arms was 6.8 and 7.7 months, respectively (HR: 1.09, 95% CI: 0.72-1.63; p = 0.69). Grade 3/4 neutropenia (GEC 43% versus GE 15%; p = 0.0008) and mucositis (GEC 9% versus GE 0%; p = 0.03) were the only statistically significant differences in grade 3/4 adverse events. PFS and OS were significantly longer in patients with rash (grade ≥1) versus no rash (grade = 0): PFS 5.5 versus 2.0 months (HR = 0.39, 95% CI: 0.26-0.6; p < 0.0001) and OS: 9.5 versus 4.0 months (HR = 0.51, 95% CI: 0.33-0.77; p = 0.0014). CONCLUSION: PFS with GEC was not significantly different to that with GE in patients with mPC. Skin rash strongly predicted erlotinib efficacy. The study was registered with ClinicalTrials.gov: NCT01303029.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Pancreáticas/tratamiento farmacológico , Administración Oral , Adulto , Anciano , Capecitabina/administración & dosificación , Capecitabina/efectos adversos , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Desoxicitidina/análogos & derivados , Esquema de Medicación , Erupciones por Medicamentos/etiología , Clorhidrato de Erlotinib/administración & dosificación , Clorhidrato de Erlotinib/efectos adversos , Exantema/inducido químicamente , Femenino , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Neoplasias Pancreáticas/mortalidad , España/epidemiología , Resultado del Tratamiento , GemcitabinaRESUMEN
Background: Disseminated germ cell cancers are at high risk of developing thromboembolic complications. We evaluated the prognostic value of venous thromboembolic events (VTE) in disseminated germ cell cancer. Methods: Patients with germ cell cancer receiving upfront platinum-containing chemotherapy between 2004 and 2014 were pooled from the Spanish Germ Cell Cancer Group (SGCCG) registry and reviewed for the presence of VTE. Results were validated in an independent international group of patients. We used a penalized Cox proportional hazards model including VTE as a time-varying covariate to identify and validate prognostic factors. All statistical tests were two-sided. Results: The SGCCG registry identified 416 patients from 14 referral institutions. With a median follow-up of 49 months, VTEs were observed in 9% of patients (n = 38). Events occurred at diagnosis, during chemotherapy, and after chemotherapy in 2.6%, 5.0%, and 1.4% of patients, respectively. VTE was associated with shorter progression-free survival (PFS; hazard ratio [HR] = 2.29, 95% confidence interval [CI] = 1.18 to 4.47, P = .02) and overall survival (OS; HR = 5.14, 95% CI = 2.22 to 11.88, P < .001). In multivariable analysis, the effect was consistent in the intermediate-risk group, both for PFS (HR = 9.52 95% CI = 2.48 to 36.58, P < .001) and OS (HR = 12.84, 95% CI = 2.01 to 82.02, P = .007). VTE at diagnosis is also an adverse prognostic variable for progression-free survival (HR = 4.64, 95% CI = 2.04 to 10.54, P < .001) and for overall survival (HR = 6.28, 95% CI = 1.68 to 17.10, P = .01). These results were validated in an independent international cohort that included 241 patients from four hospitals. Conclusions: VTE is an independent adverse prognostic factor in disseminated germ cell cancers, in particular for the intermediate prognostic group of the International Germ Cell Cancer Collaborative Group classification. The presence of VTE at diagnosis has also prognostic significance and should be further explored in future prognostic classifications.
Asunto(s)
Neoplasias de Células Germinales y Embrionarias/complicaciones , Tromboembolia Venosa/complicaciones , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bleomicina/administración & dosificación , Niño , Cisplatino/administración & dosificación , Supervivencia sin Enfermedad , Etopósido/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de Células Germinales y Embrionarias/diagnóstico , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Neoplasias de Células Germinales y Embrionarias/patología , Pronóstico , Modelos de Riesgos Proporcionales , Sistema de Registros , Tasa de Supervivencia , Adulto JovenRESUMEN
Vascular complications in transcatheter aortic valve implantation using transfemoral approach are related to higher mortality. Complete percutaneous approach is currently the preferred technique for vascular access. However, some centers still perform surgical cutdown. Our purpose was to determine complications related to vascular access technique in the population of the Spanish TAVI National Registry. From January 2010 to July 2015, 3,046 patients were included in this Registry. Of them, 2,465 underwent transfemoral approach and were treated with either surgical cutdown and closure (cutdown group, n = 632) or percutaneous approach (puncture group, n = 1,833). Valve Academic Research Consortium-2 definitions were used to assess vascular and bleeding complications. Propensity matching resulted in 615 matched pairs. Overall, 30-day vascular complications were significantly higher in the puncture group (109 [18%] vs 42 [6.9%]; relative risk [RR] 2.60; 95% confidence interval [CI] 1.85 to 3.64, p <0.001) due mostly by minor vascular events (89 [15%] vs 25 [4.1%], RR 3.56, 95% CI 2.32 to 5.47, p <0.001). Bleeding rates were lower in the puncture group (18 [3%] vs 40 [6.6%], RR 0.45, 95% CI 0.26 to 0.78, p = 0.003) mainly driven by major bleeding (9 [1.5%] vs 21 [3.4%], RR 0.43, 95% CI 0.20 to 0.93, p = 0.03). At a mean follow-up of 323 days, complication rates remained significantly different between groups (minor vascular complications 90 [15%] vs 31 [5.1%], hazard ratio 2.99, 95% CI 1.99 to 4.50, p <0.001 and major bleeding 10 [1.6%] vs 21 [3.4%], hazard ratio 0.47, 95% CI 0.22 to 1.0, p = 0.04, puncture versus cutdown group, respectively). In conclusion, percutaneous approach yielded higher rates of minor vascular complications but lower rates of major bleeding compared with the surgical cutdown, both at 30-day and at mid-term follow-up in our population.
Asunto(s)
Estenosis de la Válvula Aórtica/cirugía , Disección/métodos , Arteria Femoral , Infarto del Miocardio/epidemiología , Hemorragia Posoperatoria/epidemiología , Punciones/métodos , Sistema de Registros , Reemplazo de la Válvula Aórtica Transcatéter/métodos , Anciano , Anciano de 80 o más Años , Medios de Contraste , Femenino , Fluoroscopía , Humanos , Estimación de Kaplan-Meier , Tiempo de Internación , Masculino , Tempo Operativo , Complicaciones Posoperatorias/epidemiología , Modelos de Riesgos Proporcionales , EspañaRESUMEN
Objetivo: El infarto de miocardio es la causa más común de fallo cardíaco congestivo. El objetivo de este trabajo es evaluar, en el animal de experimentación, los efectos morfológicos e histológicos de la implantación de plasma autógeno rico en plaquetas en el corazón de ovejas previamente infartadas. Métodos: Se utilizaron 24 ovejas lacha hembras, en las que se produjo quirúrgicamente un infarto agudo de miocardio, mediante toracotomía izquierda y ligadura permanente de 2 arterias coronarias (primera y segunda diagonal). Tras la ligadura de las arterias coronarias 3 ovejas fallecieron por fibrilación ventricular. Pasadas 3 semanas de la ligadura coronaria, las ovejas fueron reoperadas por esternotomía media vertical. En 6 de ellas (grupo control) se inyectó suero fisiológico en la zona del infarto. En 15 se inyectó gel plaquetario. Todas las ovejas fueron sacrificadas a las 9 semanas de evolución de la segunda cirugía. Resultados: En los corazones tratados con plasma rico en factores de crecimiento (PRGF) destaca la neoformación vascular en los cortes de hematoxilina-eosina y de factor VIII, a diferencia de los no tratados. Conclusiones: La inyección de factores de crecimiento plaquetarios, PRGF, en el corazón de ovejas previamente infartadas favorece la mitogénesis y la angiogénesis. El uso de PRGF autógeno es sencillo y seguro, no provocando toxicidad ni desencadenando reacciones inmunológicas ni inflamatorias.
Objective: Myocardial infarction is the most common cause of congestive heart failure. The objective of this work is to evaluate, in experimental animals, morphological and histological effects of the implantation of autologous platelet-rich plasma in infarcted heart sheep. Methods: Twenty-four ewes were used, they were surgically infarcted through left thoracotomy and two coronary arteries were ligated (first and second diagonal). After coronary artery ligation three sheep died of ventricular fibrillation. Three weeks after coronary ligation, sheep were reoperated through median sternotomy. Normal saline solution was injected in the infarcted zone in 6 of them (control group) whereas platelet gel was injected in 15 of them. All sheep were euthanized at 9 weeks of evolution of the second surgery. Results: Noteworthy is the formation of new vessels in hematoxylin-eosin-stained sections and factor VIII in plasma rich in growth-factors (PRGF)-treated hearts. Conclusions: Injection of platelet growth factors, PRGF, in previously infarcted sheep hearts promotes mitogenesis and angiogenesis. The use of autologous PRGF is simple and safe, causing no toxicity or immune-inflammatory reactions.
Asunto(s)
Animales , Femenino , Infarto del Miocardio/terapia , Plasma Rico en Plaquetas , Infarto del Miocardio/patología , OvinosRESUMEN
OBJECTIVE: Myocardial infarction is the most common cause of congestive heart failure. The objective of this work is to evaluate, in experimental animals, morphological and histological effects of the implantation of autologous platelet-rich plasma in infarcted heart sheep. METHODS: Twenty-four ewes were used, they were surgically infarcted through left thoracotomy and two coronary arteries were ligated (first and second diagonal). After coronary artery ligation three sheep died of ventricular fibrillation. Three weeks after coronary ligation, sheep were reoperated through median sternotomy. Normal saline solution was injected in the infarcted zone in 6 of them (control group) whereas platelet gel was injected in 15 of them. All sheep were euthanized at 9 weeks of evolution of the second surgery. RESULTS: Noteworthy is the formation of new vessels in hematoxylin-eosin-stained sections and factor viii in plasma rich in growth-factors (PRGF)-treated hearts. CONCLUSIONS: Injection of platelet growth factors, PRGF, in previously infarcted sheep hearts promotes mitogenesis and angiogenesis. The use of autologous PRGF is simple and safe, causing no toxicity or immune-inflammatory reactions.
Asunto(s)
Infarto del Miocardio/terapia , Plasma Rico en Plaquetas , Animales , Femenino , Infarto del Miocardio/patología , OvinosRESUMEN
PURPOSE: The prognosis of patients with unresectable M0 gastric cancer remains very poor. We performed a phase II trial to explore the efficacy and toxicity of induction irinotecan-cisplatin (IC) followed by concurrent irinotecan-cisplatin and radiotherapy (IC/RT) in this setting. METHODS AND MATERIALS: Patients with unresectable M0 gastric (GC) or oesophageal-gastric junction (EGJC) adenocarcinomas were treated with two courses of IC (irinotecan, 65 mg/m(2); cisplatin, 30 mg/m(2) on days 1 and 8 every 21 days) followed by IC/RT (daily radiotherapy-45 Gy-with concurrent IC: irinotecan, 65 mg/m(2), and cisplatin, 30 mg/m(2), on days 1, 8, 15, and 22). Resectability was reassessed after this treatment, and surgical resection was performed if feasible. The primary endpoint was the R0 resection rate after induction treatment. RESULTS: Seventeen patients were included in the study (EGJC: 6; GC: 11). An R0 resection was achieved in only 5 patients (29%), and according to the design of the trial (Simon's optimal two-stage) accrual of patients was terminated after the first stage. No patient died during IC, whereas 3 patients (24%) died during IC/RT and one of 5 resected patients (20%) died during the first 30 days after resection. The median survival was 10.5 months, and the actuarial 2-year survival rate was 27%. CONCLUSIONS: Induction IC followed by IC/RT showed poor efficacy and significant toxicity in patients with unresectable GC/EGJC.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Esofágicas/tratamiento farmacológico , Unión Esofagogástrica/patología , Neoplasias Gástricas/tratamiento farmacológico , Adenocarcinoma/patología , Adenocarcinoma/radioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Camptotecina/administración & dosificación , Camptotecina/análogos & derivados , Cisplatino/administración & dosificación , Terapia Combinada , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/radioterapia , Estudios de Seguimiento , Humanos , Irinotecán , Neoplasias Gástricas/patología , Neoplasias Gástricas/radioterapia , Tasa de SupervivenciaRESUMEN
Postcardiotomy sternal wound complications remain challenging. We looked at the effects of plasma rich in growth factors (PRGF) as an agent on sternal bone healing. In 24 female sheep, a median sternotomy was surgically created. In 12 of them (group control) the sternum was closed with three figure-of-eight wires. In 12 (group PRGF) three clots of autologous PRGF were applied over the sternum after its closure in the same manner as the control group. All sheep were killed at the nine-week follow-up. The sternum and the surrounding soft tissue was removed and fixed in formaldehyde. Transversal sections of the bone were obtained, decalcified and stained with hematoxylin and eosin. In the control group, we found extensive cartilaginous areas. In the PRGF group, the presence of trabecular bone tissue was common, with formation of hematopoietic medullary tissue. The process of new bone formation was accelerated in the PRGF group at the nine-week follow-up. In contrast, in the control group, the presence of cartilaginous tissue was the most common finding.
Asunto(s)
Terapia Biológica/métodos , Péptidos y Proteínas de Señalización Intercelular/sangre , Osteogénesis , Plasma Rico en Plaquetas , Esternotomía , Esternón/cirugía , Cicatrización de Heridas , Animales , Condrogénesis , Estudios de Factibilidad , Femenino , Modelos Animales , Ovinos , Esternotomía/efectos adversos , Esternón/metabolismo , Esternón/patología , Factores de TiempoRESUMEN
PURPOSE: To determine in a Phase II trial whether preoperative irinotecan-cisplatin (IC) followed by concurrent IC therapy and radiotherapy (IC/RT) improved outcome in patients with resectable, locally advanced gastric adenocarcinoma (GC) or esophagogastric junction cancer (EGJC). PATIENTS AND METHODS: Patients with resectable Stage II-IV, M0 GC or EGJC made up the study population. The primary endpoint was pathologic complete response (pCR). Two courses of IC (irinotecan, 65 mg/m(2); cisplatin, 30 mg/m(2) on Days 1 and 8 every 21 days) were given. Patients without progression then received IC/RT, consisting of daily radiotherapy (45Gy) with concurrent IC (irinotecan, 65 mg/m(2); cisplatin, 30 mg/m(2) on Days 1, 8, 15, and 22). Surgical resection was performed, if feasible, 5-8 weeks after the end of radiotherapy. RESULTS: Twenty-three patients were included in the study: 10 with EGJC and 13 with GC. Two patients (9%) achieved pCR. The incidences of Grade 3-4 toxicities were as follows: IC: neutropenia 35% (febrile 13%), anemia 22%, diarrhea 22%, emesis 8%; IC/RT: neutropenia 52% (febrile 5%), asthenia 19%, anemia 9%, emesis 9%, diarrhea 5%, cardiotoxicity 5%. No patients died during IC or IC/RT. R0 resection was achieved in 15 patients (65%). Median survival was 14.5 months, and the actuarial 2-year survival rate was 35%. CONCLUSIONS: Preoperative IC followed by IC/RT resulted in moderate response and resection rates with mild toxicity in patients with GC and EGJC.
Asunto(s)
Adenocarcinoma , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Esofágicas , Unión Esofagogástrica , Neoplasias Gástricas , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Adenocarcinoma/radioterapia , Adenocarcinoma/cirugía , Algoritmos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Camptotecina/administración & dosificación , Camptotecina/efectos adversos , Camptotecina/análogos & derivados , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Terapia Combinada/efectos adversos , Terapia Combinada/métodos , Esquema de Medicación , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/radioterapia , Neoplasias Esofágicas/cirugía , Humanos , Irinotecán , Periodo Preoperatorio , Estudios Prospectivos , Inducción de Remisión , España , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Neoplasias Gástricas/radioterapia , Neoplasias Gástricas/cirugía , Tasa de SupervivenciaRESUMEN
OBJECTIVES: The utility of many molecules as tumor markers in melanoma has been investigated with different results. The aims of this study was to compare the value of tyrosinase mRNA by reverse transcription polymerase chain reaction (RT-PCR) in peripheral blood and of serum S-100 protein in patients with melanoma at different stages of disease. METHODS: We have studied 90 peripheral blood samples corresponding to 90 patients that had been diagnosed with melanoma. The clinical staging at the time of blood sampling was performed according to the American Join Committee on Cancer guidelines. S-100 protein in serum was measured by enzyme-linked immunosorbent assay (normal range: 0-0.150 microg) and the presence of tyrosinase mRNA was assessed by RT-PCR. RESULTS: Median progression-free survival was 281 days for tyrosinase positive patients and it has not been reached for tyrosinase negative patients (P = 0.03). Median progression free survival was 213 days for patients with elevated serum S-100 and it has not been reached for patients with normal level of serum S-100 (P < 0.001). Median overall survival (OS) was 396 days for tyrosinase positive patients and it has not been reached for negative patients (P = 0.0096). Median OS was 282 days for patients with elevated serum S-100 and it has not been reached for patients with normal level of serum S-100 (P < 0.001). In a multivariate analysis, both markers have significant prognostic value for time to progression and for survival (chi(2) test). CONCLUSIONS: RT-PCR for tyrosinase mRNA and S-100 are significant prognostic factors for progression-free survival and OS in melanoma. S-100 has higher sensitivity and specificity than tyrosinase.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Melanoma/metabolismo , Monofenol Monooxigenasa/metabolismo , Proteínas S100/metabolismo , Neoplasias Cutáneas/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Melanoma/sangre , Melanoma/genética , Persona de Mediana Edad , Monofenol Monooxigenasa/genética , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Neoplásico/genética , ARN Neoplásico/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sensibilidad y Especificidad , Neoplasias Cutáneas/sangre , Neoplasias Cutáneas/genética , Tasa de SupervivenciaRESUMEN
AIMS AND BACKGROUND: The purpose of the study was to test the immunological and clinical effects of infusions of dendritic cells pulsed with autologous tumor lysate in patients with advanced cancer. PATIENTS AND METHODS: Peripheral blood mononuclear cells from 15 patients with metastatic cancer (melanoma in 10, lung cancer in 2, renal cell carcinoma in 1, sarcoma in 1, breast cancer in 1) were harvested by leukapheresis after mobilization with GM-CSF (5 microg/kg/day s.c. for 4 days). Mononuclear cells were separated and cultured in GM-CSF (1000 U/ml) and interleukin-4 (1000 U/ml) for 7 days. Phenotype was assessed by 2-color flow cytometry and immunocytochemistry. On day 6, dendritic cells were pulsed with 1 g of fresh autologous tumor lysate for 24 h and infused intravenously. Interleukin-2 (6 million IU), interferon a (4 million IU) and GM-CSF (400 microg) were injected s.c. daily for 10 days beginning on the day of dendritic cell infusion. Treatment was repeated every 21 days for 3 courses. RESULTS: The morphology, immunocytochemistry and phenotype of cultured cells was consistent with dendritic cells: intense positivity for HLA-DR and CD86, with negativity for markers of other lineages, including CD3, CD4, CD8 and CD14. More than 5 x 10(7) dendritic cells were injected in all patients. Nine patients developed >5 mm delayed type cutaneous hypersensitivity reactions to tumor lysate+/-GM-CSF after the first immunization (larger than GM-CSF in all cases). Median delayed type cutaneous hypersensitivity to lysate +/- GM-CSF was 3 cm after the third immunization. One melanoma patient with skin, liver, lung and bone metastases had a partial response lasting 8 months (followed by progression in the brain). Seven patients had stable disease for >3 months, and 7 had progression. CONCLUSIONS: Infusion of tumor lysate-pulsed dendritic cells induces a strong cell-mediated antitumor immune reaction in patients with advanced cancer and has some clinical activity.
Asunto(s)
Células Dendríticas/inmunología , Células Dendríticas/trasplante , Inmunoterapia Adoptiva , Neoplasias/terapia , Adulto , Anciano , Antígenos CD/metabolismo , Femenino , Citometría de Flujo , Humanos , Hipersensibilidad Tardía , Inmunohistoquímica , Inmunofenotipificación , Inmunoterapia Adoptiva/efectos adversos , Masculino , Persona de Mediana Edad , Neoplasias/inmunología , Proyectos Piloto , Trasplante AutólogoRESUMEN
PURPOSE: To assess the efficacy of a risk-adapted treatment policy for patients with stage I seminoma by using universally accepted risk criteria. PATIENTS AND METHODS: Between 1999 and 2003, 314 patients with clinical stage I seminoma after orchiectomy were prospectively included. One hundred patients (31.8%) presented no risk factors and were managed with surveillance. In contrast, 131 patients (41.7%) had tumors larger than 4 cm, 33 patients (10.5%) had rete testis involvement, and 50 patients (15.9%) had both risk factors. All the latter received two courses of adjuvant carboplatin. RESULTS: Chemotherapy was well tolerated, as only 17 patients (7.9%) presented grade 3 to 4 toxicity. Relapses were observed in six patients (6.0%) on surveillance and in seven patients (3.3%) treated with carboplatin (0.8% of tumors larger than 4 cm, 9.1% of those involving the rete testis, and 6.0% of patients with both risk criteria). All were located at the retroperitoneum, except for one at the spermatic cord. Median tumor size was 25 mm (range, 11 to 70 mm), and median time to relapse was 9 months (range, 4 to 28 months). All patients were rendered disease-free with chemotherapy (etoposide plus cisplatin). Median follow-up was 34 months (range, 12 to 72 months). The actuarial 5-year disease-free survival rate was 93.4% for patients on surveillance and 96.2% for patients treated with adjuvant chemotherapy. Overall 5-year survival was 100%. CONCLUSION: Adjuvant carboplatin is effective in reducing the relapse rate in patients with stage I seminoma and risk factors. A risk-adapted strategy is safe and feasible and should be considered an alternative to systematic approaches, such as irradiation, chemotherapy, or surveillance.
Asunto(s)
Antineoplásicos/uso terapéutico , Carboplatino/uso terapéutico , Seminoma/tratamiento farmacológico , Neoplasias Testiculares/tratamiento farmacológico , Adolescente , Adulto , Factores de Edad , Anciano , Antineoplásicos/efectos adversos , Carboplatino/efectos adversos , Quimioterapia Adyuvante , Gonadotropina Coriónica Humana de Subunidad beta/sangre , Supervivencia sin Enfermedad , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Recurrencia Local de Neoplasia/prevención & control , Estadificación de Neoplasias , Neutropenia/inducido químicamente , Orquiectomía , Estudios Prospectivos , Factores de Riesgo , Seminoma/patología , Seminoma/cirugía , Neoplasias Testiculares/patología , Neoplasias Testiculares/cirugía , Resultado del Tratamiento , Vómitos/inducido químicamenteRESUMEN
AIMS AND BACKGROUND: Although there is no established tumor marker of proven value for patients with melanoma, high serum levels of S-100B protein have been found in patients with melanoma and distant metastases. This study was performed to assess the prognostic value of this marker. METHODS AND STUDY DESIGN: Serum S-100B protein was measured by means of the LIA-mat System 300 (Sangtec S-100B LIA, AB Sangtec Medical, Bromma, Sweden) in 85 patients with melanoma. RESULTS: Mean serum S-100B protein was 0.075 microg/L (range, 0.001-0.470) in 66 patients with non-metastatic melanoma (stage I-III) versus 0.441 microg/L (range, 0.001-16.840) in 19 patients with metastatic melanoma (stage IV) (P <0.001, Mann Whitney U test). The median follow-up time was 329 days. Serum levels above 0.150 microg/L were found in 10 of patients with non-metastatic melanoma (15.2%) and in 17 of 19 patients with metastatic disease (89.4%). Median survival was 256 days for the 27 patients with serum S-100B levels above 0.150 microg/L versus 561 days for the 58 patients with normal values (P <0.3973). CONCLUSION: Serum S-100B is a useful tumor marker in melanoma.
Asunto(s)
Biomarcadores de Tumor/sangre , Melanoma/sangre , Proteínas S100/sangre , Neoplasias Cutáneas/sangre , Adulto , Anciano , Femenino , Humanos , Masculino , Melanoma/patología , Persona de Mediana Edad , Estadificación de Neoplasias , Factores de Crecimiento Nervioso , Valor Predictivo de las Pruebas , Pronóstico , Subunidad beta de la Proteína de Unión al Calcio S100 , Neoplasias Cutáneas/patologíaRESUMEN
BACKGROUND: Invasive candidiasis is an increasing problem in neonatal intensive care units worldwide and is an important cause of morbidity, mortality and prolongation of hospital stay. Despite administration of amphotericin B, invasive candidiasis in neonates is sometimes complicated by persistent fungemia and refractory invasive candidiasis. The problem has been augmented by the increasing prevalence of non-albicans species that often are resistant to fluconazole and to amphotericin B. POPULATION AND METHODS: The population consisted of 1 term and 9 premature neonates with invasive candidiasis caused by Candida albicans (n = 4), Candida parapsilosis (n = 3), Candida tropicalis (n = 2) and Candida glabrata (n = 1). Despite initial therapy with deoxycholate amphotericin B, blood cultures remained positive in all patients for 13-49 days. Invasive candidiasis progressed to meningitis and enlarging renal Candida bezoars in the kidney of one patient and an enlarging atrial vegetation in another. Another patient developed severe hypokalemia refractory to potassium supplementation. Two of the C. albicans and all of the non-albicans Candida isolates were resistant to fluconazole; the C. glabrata isolate was resistant to amphotericin B. Amphotericin B was discontinued and caspofungin initiated in all patients in a dosage of 1 mg/kg/d for 2 days followed by 2 mg/kg/d. RESULTS: All positive blood cultures cleared between 3 and 7 days after initiation of caspofungin, the atrial vegetation resolved and the renal Candida bezoars disappeared. Renal and hepatic function tests did not show any values above normal throughout caspofungin therapy. There were no attributable clinical adverse events during the administration of caspofungin in any of the patients. CONCLUSIONS: Caspofungin was effective, safe and well-tolerated as an alternative therapy for persistent and progressive candidiasis in those neonates who were unresponsive to or intolerant of deoxycholate amphotericin B.
Asunto(s)
Antifúngicos/uso terapéutico , Candidiasis/tratamiento farmacológico , Péptidos Cíclicos/uso terapéutico , Candida/efectos de los fármacos , Candida/aislamiento & purificación , Candidiasis/microbiología , Caspofungina , Farmacorresistencia Fúngica , Equinocandinas , Humanos , Recién Nacido , Recien Nacido Prematuro , Lipopéptidos , Pruebas de Sensibilidad Microbiana , Péptidos Cíclicos/efectos adversosAsunto(s)
Leiomiosarcoma/complicaciones , Leiomiosarcoma/secundario , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/secundario , Osteoartropatía Hipertrófica Secundaria/etiología , Neoplasias Uterinas/patología , Femenino , Humanos , Persona de Mediana Edad , Osteoartropatía Hipertrófica Secundaria/diagnósticoRESUMEN
BACKGROUND: Cisplatin-based combinations are considered to be the standard treatment for advanced transitional cell carcinoma (TCC) of the urothelium. Many of the patients are elderly with concomitant diseases or impaired renal function. We studied the tolerance and activity of the gemcitabine/carboplatin combination as a therapeutic alternative. METHODS: Patients with locally advanced or metastatic TCC of the urothelium were treated with gemcitabine 1000 mg/m(2) on Days 1 and 8 and carboplatin area under the concentration-time curve 5 on Day 1 every 21 days. Patients with creatinine clearance of 30 mL/min or above and Karnofsky performance status (KPS) scores 60 or above were enrolled. RESULTS: A total of 227 cycles were administered to 41 patients, with an average of 5.5 cycles per patient (range, 1-8 cycles). Creatinine clearance was below 60 mL/min in 54% of patients, KPS was 70 or below in 37% of patients, and 37% of patients were 70 years old or older. Hematologic toxicity was mainly Grade 3/4 neutropenia in 63%, Grade 3/4 thrombocytopenia in 32%, and Grade 3/4 anemia in 54% of patients. There were only three episodes of febrile neutropenia and one death from neutropenic sepsis. Nonhematologic toxicity was mild, with asthenia as the most frequently reported event. We obtained 6 complete and 17 partial responses, for an overall response rate of 56.1% (95% confidence interval [CI], 40.6-71.6%). Progression-free survival was 7.2 months (95% CI, 5.7-8.5) and median survival was 10.1 months (95% CI, 8.8-12.2). CONCLUSIONS: The combination of gemcitabine plus carboplatin achieves a similar result to doublets using cisplatin. It has an acceptable toxicity profile and enables patients with impaired renal function and/or poor performance status and elderly patients to be treated.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Transicionales/tratamiento farmacológico , Desoxicitidina/análogos & derivados , Neoplasias Urológicas/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino/administración & dosificación , Carcinoma de Células Transicionales/mortalidad , Carcinoma de Células Transicionales/patología , Desoxicitidina/administración & dosificación , Femenino , Humanos , Metástasis Linfática , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Pronóstico , Calidad de Vida , Tasa de Supervivencia , Neoplasias Urológicas/diagnóstico , Neoplasias Urológicas/mortalidad , Neoplasias Urológicas/patología , GemcitabinaRESUMEN
La inflamación aguda del oido medio es uno de los procesos infecciosos más frecuentes en la infancia. La elevada recurrencia de esta enfermedad, como consecuencia de diversos factores analizados en el presente artículo, conlleva una tasa de secuelas que, mediante un diagnóstico temprano y un adecuado tratamiento, podría ser reducida al mínimo.
Asunto(s)
Niño , Otitis/diagnóstico , Otitis/etiología , Otitis/terapiaRESUMEN
Se revisaron los expedientes de 17 niños con diagnóstico de osteosarcoma tratados en Hospital Nacional de Niños en un periodo de nueve años; 10 del sexo femenino y siete del masculino, con edades entre los cinco y 15 años, en un periodo de nueve años. En 47% estaba localizado en fémur, 23% en tibia, 23% en húmero y en 5% en peroné; todos ingresaron sin metástasis. En los 17 había ruptura de la corteza e infiltración a tejidos blandos, 11 tenían invasión del disco epifisiario, dos del cartílago y uno del espacio articular; dos ingresaron con fractura patológica. Siete pacientes fueron desarticulados, en seis se llevó a cabo la resección en bloque del tumor y cuatro fueron amputados. Cinco pacientes, recibieron adriamicina y methotrexate iv postoperatorio por 18 meses o hasta la recaída: todos fallecieron (x=24 meses) debido a metástasis pulmonares. Otros cuatro que recibieron A, CFM, VCR yMTX iv. posterior a la desarticulación en tres casos y a la amputación en uno, también fallecieron por metástasis (x=15 meses). De dos pacientes tratados con este mismo esquema pero iniciado seis semanas antes de la resección en bloque del tumor, uno falleció a los 18 meses por metástasis pulmonares y el otro tiene una sobrevida de 84 meses. Los otros seis pacientes recibieron A intra arterial preoperatoria y CDDP iv. en dos casos: dos fallecieron a los 24 meses, y cuatro sobreviven en remisión con ocho a 32 meses de evolución. Los resultados sugieren que la quimioterapia ia y sistémica pre y post operatoria y una cirurgía conservadora es una conducta que se puede a seguir en el futuro
Asunto(s)
Preescolar , Niño , Adolescente , Neoplasias Óseas/tratamiento farmacológico , Sarcoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica , Costa Rica , Infusiones Intraarteriales , Sarcoma/mortalidad , Sarcoma/cirugíaRESUMEN
Se estudió a 105 neonatos, admitidos al Servicio de Neonatología y 36 niños mayores que ingresaron a otros servicios del Hospital Nacional de Niños. Todos ellos presentaron uno o más signos de la sintomatología clásica del síndrome de TORCH. Se determinó el citomegaloviruria en 10 de los niños (7%) y se detectó IgM e IgG específica en el suero de cada uno de ellos. Cuatro de los pacientes fueron estudiados durante la primera semana de vida, por lo cual pudo concluirse que eran infecciones in utero. Cuatro de ellos tuvieron su ingreso después de la primera semana por lo cual no se pudo concluir certeramente el tipo de infección, aunque los signos, patología y evolución hicieron inclinarse fuertemente hacia una infección congénita. Se logró determinar infección natal o postnatal en dos de los casos. Se presentan las características de las madres como edad, seropositividad, paridad, y otras, y se discute ampliamente cuál tipo de infección (primaria o reactivación es más importante en Costa Rica