RESUMEN
BACKGROUND: Orofacial clefts occur when the lips or the roof of the mouth do not fuse properly during the early weeks of pregnancy. There is strong evidence that periconceptional use of folic acid can prevent neural tube defects but its effect on oral clefts has generated debate. AIM: To identify factors associated with suboptimal periconceptional use of folic acid and its potential effect on oral clefts. DESIGN AND SETTING: The population-based infant cohort of the national Growing Up in Ireland study, which consists of 11 134 9-month-old infants. METHOD: Data collection comprised questionnaires conducted by interviewers with parents in parents' homes. Characteristics of mothers who did or did not take folic acid before and during pregnancy, as well as the effect of folic acid use on the prevalence of cleft lip and palate were recorded. RESULTS: The prevalence of cleft lip and palate was 1.98 (95% confidence interval [CI] = 1.31 to 2.99) per 1000 9-month-olds. The odds ratio for cleft lip was 4.36-fold higher (95% CI = 1.55 to 12.30, P = 0.005) for infants of mothers who did not take folic acid during the first 3 months of pregnancy, when compared with those who did have a folate intake during the first trimester. Folic acid use was suboptimal in 36.3% (95% CI = 35.4 to 37.2) of the sample. CONCLUSION: These findings support the hypothesis that taking folic acid may partially prevent cleft lip and palate. They are particularly relevant for GPs, because they are usually the first port of call for women before and during early pregnancy.
Asunto(s)
Labio Leporino/prevención & control , Fisura del Paladar/prevención & control , Ácido Fólico/uso terapéutico , Atención Preconceptiva/métodos , Labio Leporino/epidemiología , Fisura del Paladar/epidemiología , Estudios Transversales , Femenino , Humanos , Lactante , Irlanda/epidemiología , Masculino , Embarazo , Prevalencia , Factores de Riesgo , Distribución por SexoRESUMEN
BACKGROUND: The aim of this retrospective study was to evaluate the efficacy and safety of weekly high-dose 5-fluorouracil (5-FU)/folinic acid (FA) as 24-h infusion (AIO regimen) plus irinotecan in patients with histologically proven metastatic gastroesophageal adenocarcinoma (UICC stage IV). MATERIAL/METHODS: From 08/1999 to 12/2008, 76 registered, previously untreated patients were evaluable. Treatment regimen: irinotecan (80 mg/m²) as 1-h infusion followed by 5-FU (2000 mg/m²) combined with FA (500 mg/m²) as 24-h infusion (d1, 8, 15, 22, 29, 36, qd 57). RESULTS: Median age: 59 years; male/female: 74%/26%; ECOG ≤1: 83%; response: CR: 1%, PR: 16%, SD: 61%, PD: 17%, not evaluable in terms of response: 5%; tumor control: 78%; median OS: 11.2 months; median time-to-progression: 5.3 months; 1-year survival rate: 49%; 2-year survival rate: 17%; no evidence of disease: 6.6%; higher grade toxicities (grade 3/4): anemia: 7%, leucopenia: 1%, ascites: 3%, nausea: 3%, infections: 12%, vomiting: 9%, GI bleeding of the primary tumor: 4%, diarrhea: 17%, thromboembolic events: 4%; secondary metastatic resection after downsizing: 16 patients (21%), R-classification of secondary resections: R0/R1/R2: 81%/6%/13%, median survival of the 16 patients with secondary resection: 23.7 months. CONCLUSIONS: Combined 5-FU/FA as 24-h infusion plus irinotecan may be considered as an active palliative first-line treatment accompanied by tolerable toxicity; thus offering an alternative to cisplatin-based treatment regimens. Thanks to efficient interdisciplinary teamwork, secondary metastatic resections could be performed in 16 patients. In total, the patients who had undergone secondary resection had a median survival of 23.7 months, whereas the median survival of patients without secondary resection was 10.1 months (p≤0.001).
Asunto(s)
Camptotecina/análogos & derivados , Neoplasias Esofágicas/secundario , Unión Esofagogástrica/patología , Fluorouracilo/uso terapéutico , Leucovorina/uso terapéutico , Cuidados Paliativos , Neoplasias Gástricas/secundario , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/secundario , Adenocarcinoma/cirugía , Adulto , Anciano , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Camptotecina/administración & dosificación , Camptotecina/efectos adversos , Camptotecina/uso terapéutico , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Neoplasias Esofágicas/diagnóstico por imagen , Neoplasias Esofágicas/cirugía , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Infusiones Intravenosas , Irinotecán , Estimación de Kaplan-Meier , Leucovorina/administración & dosificación , Leucovorina/efectos adversos , Masculino , Persona de Mediana Edad , Pronóstico , Cintigrafía , Neoplasias Gástricas/diagnóstico por imagen , Neoplasias Gástricas/cirugía , Resultado del TratamientoRESUMEN
BACKGROUND: The aim of this study was to evaluate the efficacy and toxic side effects of combined gemcitabine plus weekly high-dose 5-Fluorouracil (5-FU) as 24h-infusion in patients with metastatic pancreatic cancer (UICC IV) as validation group of an earlier phase II study. Primary endpoints were to assess the response and tumour control rate. MATERIAL/METHODS: This study comprised 60 prospectively registered patients with metastatic pancreatic cancer (UICC IV). A locally advanced disease was defined as exclusion criteria. The treatment schedule was weekly gemcitabine (1.000 mg/m(2)) as a 0.5h-infusion combined with 5-FU (2.000 mg/m(2)) as a 24h-infusion on day 1, 8 and 15 every 28 days. RESULTS: Response rate (CR+PR) was achieved in 7% of the patients, tumour control rate (CR+PR+SD) was achieved in 59%. Median time-to-progression was 4 months, median overall survival was 7.3 months (95% CI 5.4-9.1). The median survival of patients with normal CEA value was 10.6 months (95% CI 7.8-13.4); with a normal CA 19-9 median survival was 10.1 months (95% CI 4.6-15.7) and with ECOG performance status 0 median survival was 10.1 months (95% CI 8.6-15.3). As higher grade toxicity (grade 3/4) leukopenia (15%), anaemia (10%) and thrombopenia (5%) were observed. Nausea and diarrhea (grade 3/4) occurred in 5% of the patients and vomiting in 2%. CONCLUSIONS: The administration of gemcitabine and 5-FU as a 24h-infusion is feasible and offers good tumour control rate accompanied by tolerable toxicity. The subgroup of patients with a good performance status (ECOG 0) and tumour markers within the normal range benefit from the gemcitabine combination therapy.
Asunto(s)
Antineoplásicos/uso terapéutico , Desoxicitidina/análogos & derivados , Fluorouracilo/administración & dosificación , Fluorouracilo/uso terapéutico , Cuidados Paliativos , Neoplasias Pancreáticas/tratamiento farmacológico , Adulto , Anciano , Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/metabolismo , Antígeno Carcinoembrionario/metabolismo , Ensayos Clínicos Fase II como Asunto , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Desoxicitidina/uso terapéutico , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Fluorouracilo/efectos adversos , Humanos , Infusiones Intravenosas , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Pronóstico , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos , GemcitabinaRESUMEN
BACKGROUND: In 2003 Wein et al. published data after a short median follow up (23 months). Here we report on the long-term results. MATERIAL/METHODS: The patients (n=20) received a neoadjuvant treatment regimen comprising biweekly 85 mg/m2 oxaliplatin (L-OHP) (2h-infusion, d 1, 15, 29 qd 57) and 500 mg/m2 calcium folinic acid (FA) (1-2h-infusion, d 1, 8, 15, 22, 29, 36 qd 57) followed by 2600 mg/m2 5-Fluorouracil (5-FU) (24h-infusion, d 1, 8, 15, 22, 29, 36 qd 57). Two cycles of chemotherapy were administered, with a third being added when the treatment was well tolerated. Thereafter, curative resection of the liver metastases was attempted. RESULTS: After neoadjuvant therapy, imaging procedures revealed complete remission in 2 patients (10%) and partial remission in 18 patients (90%). Diarrhea (Common Toxicity Criteria toxicity grade 3) was observed in 6 patients (30%) as main symptom of toxicity, followed by vomiting in 3 patients (15%). Higher grade sensomotoric neuropathy did not present. The curative resectability rate (R0) was 80%. In 9 out of 18 patients (50%) undergoing surgical intervention minor postoperative complications occurred. No postoperative mortality was observed. Over a median follow up of 45,5 months the median survival of all patients is 3.0 years and the 5-year overall survival rate is 40%. The 5-year disease-free survival rate is 25%. CONCLUSIONS: Neoadjuvant treatment with 5-FU combined with FA and L-OHP proved to be highly effective and well tolerated. Disease-free survival rates and median overall survival rates are promising.
Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias Colorrectales/patología , Fluorouracilo/uso terapéutico , Leucovorina/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Compuestos Organoplatinos/uso terapéutico , Anciano , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Bombas de Infusión Implantables , Estimación de Kaplan-Meier , Leucovorina/administración & dosificación , Leucovorina/efectos adversos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Recurrencia Local de Neoplasia/tratamiento farmacológico , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/efectos adversos , Oxaliplatino , Cooperación del Paciente , Factores de TiempoRESUMEN
In the majority of patients with oesophageal carcinoma, curative treatment proves to be impossible when diagnosis was established; therefore, most of the patients are candidates for palliative chemotherapy. The aim of this phase II study was to evaluate the efficacy and safety of 5-fluorouracil/folinic acid (AIO regimen) plus irinotecan in patients with locally advanced or metastatic carcinoma of the oesophagus. The methods used a prospective phase II trial, start: November 2002; patients: n=25; chemotherapy: irinotecan (80 mg/m2) as a 1-h infusion and 5-fluorouracil (2000 mg/m2) with sodium folinic acid (500 mg/m2) as a 24-h infusion on days 1, 8, 15, 22, 29 and 36, repeated on day 57. Last date of evaluation: 28 February 2007; n=24; adenocarcinoma: n=13, squamous cell carcinoma (SCC): n=11; UICC III/IV: 3/21; grading G1/G2/G3/G4: 0/8/12/4; median age: 58 years (range 44-75); men/women: 19/5; Eastern Cooperative Oncology Group index 0/1/2: 3/17/4; applications: 460. Higher-grade toxicity: grade 3 diarrhoea: n=2, grade 4 diarrhoea: n=1, grade 4 vomiting: n=1, grade 4 nausea: n=1, grade 3 fatigue: n=1, grade 3 hyponatraemia: n=2, grade 4 elevation of creatinine: n=1, thrombosis of the vena subclavia: n=1, ischaemic lesion of the brain stem: n=1. Three patients died after two chemotherapeutic applications because of high tumour burden. Evaluable for response: n=19. Partial response: n=8 (33%), stable disease: n=9 (38%), progressive disease: n=2 (8%), not evaluable: n=5 (21%). Time-to-progression: 6.6 months (range 1.6-24.6). Total median survival: 13.6 months (median survival of adenocarcinoma: 20.3 months, median survival of SCC: 10.0 months). Secondary resection (R0): n=3. In oesophageal carcinomas, the AIO regimen plus irinotecan is excellently manageable as an outpatient treatment and shows efficacy in adenocarcinomas and SCCs of the oesophagus.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Neoplasias Esofágicas/tratamiento farmacológico , Adenocarcinoma/secundario , Adenocarcinoma/cirugía , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Células Escamosas/secundario , Carcinoma de Células Escamosas/cirugía , Terapia Combinada , Esquema de Medicación , Neoplasias Esofágicas/cirugía , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Estimación de Kaplan-Meier , Leucovorina/administración & dosificación , Leucovorina/efectos adversos , Masculino , Persona de Mediana Edad , Cuidados Paliativos , Estudios Prospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Tumor response to radiochemotherapy (RCT) varies considerably, even among patients treated in accordance with the same protocol. The aim of the present study was to test the predictive value of the cell-cycle inhibitor p27kip1 with regard to neoadjuvant RCT response in rectal cancer. MATERIALS AND METHODS: P27kip1 was evaluated by immunohistochemistry in pretreatment biopsy material obtained from 42 patients with rectal cancer treated uniformly in accordance with an identical prospective neoadjuvant RCT protocol (CAO/AIO/ARO-94). Four expression patterns (staining intensity [-,+,++,+++] and the percentage of positive cells, evaluated separately for nuclei and cytoplasm) of p27kip1 were investigated for correlation with tumor response, which was assessed in the resected surgical specimen using a histopathological five-point grading system. Additionally, p27(kip1) expression was investigated for correlation with several pathological features, overall survival, and disease-free survival. RESULTS: p27kip1 expression was as follows: nuclear intensity: -: 8, +: 19, ++: 11, +++: 4 cases, median percentage of positive cells: 18.75%; cytoplasmic intensity: -: 0, +: 25, ++: 12, +++: 3 cases, median percentage of positive cells: 70%. Histopathological tumor regression was acceptable in 30 patients (3 complete; 27 good) and inadequate in 12 patients (7 moderate; 5 minimal). No tumor failed to show some regression. No significant correlation was found between any of the p27kip1 expression patterns and RCT response, tumor differentiation (low grade versus high grade), cT- and ypT-category, UICC stage, overall survival, and disease-free survival. CONCLUSIONS: p27kip1 cannot aid the individualization of multimodal treatment strategies in rectal cancer, nor can it serve as a predictor of survival.
Asunto(s)
Adenocarcinoma/metabolismo , Adenocarcinoma/terapia , Biomarcadores de Tumor/biosíntesis , Proteínas de Ciclo Celular/biosíntesis , Quinasas Ciclina-Dependientes/biosíntesis , Neoplasias del Recto/metabolismo , Neoplasias del Recto/terapia , Proteínas Supresoras de Tumor/biosíntesis , Adulto , Anciano , Antimetabolitos Antineoplásicos/uso terapéutico , Colectomía/métodos , Terapia Combinada , Inhibidor p27 de las Quinasas Dependientes de la Ciclina , Femenino , Fluorouracilo/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Radioterapia Adyuvante/métodos , Inducción de Remisión , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
Schizophrenia is associated with cortical asymmetries concentrated in the left fronto-temporal hemisphere. In order to look for functional asymmetries between the two hemispheres, the stimulus-response times of patients were split into smaller periods and the interhemispheric and intrahemispheric correlations between these periods were investigated. Three groups were compared to each other: 22 patients with schizophrenia (Diagnostic and Statistical Manual of Mental Disorders, 4th edn; DSM-IV) treated with neuroleptics; 24 psychiatric neuroleptic-treated patients without schizophrenia; and 30 healthy subjects. All subjects were investigated by simple (one stimulus-one response) and complex (two stimuli-two responses), auditory and visual, right-hemispheric and left-hemispheric stimulus-response tasks. There were no intrahemispheric but significant interhemispheric correlations between the two auditory and between the two visual time fragments in both the healthy and the neuroleptic control group. In contrast there was a significant intrahemispheric correlation between the auditory and visual time fragment in the left hemisphere of patients with schizophrenia and no interhemispheric correlation between the auditory times. The reduction of the interhemispheric auditory correlation is interpreted as an auditory disintegration, the appearance of the left-hemispheric audiovisual correlation as an audiovisual 'hyperintegration' in patients with schizophrenia. It is questionable as to whether these findings are due to schizophrenia or to the neuroleptic treatment.