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Erupciones Acneiformes/tratamiento farmacológico , Antineoplásicos Inmunológicos/efectos adversos , Cetuximab/efectos adversos , Erupciones por Medicamentos/tratamiento farmacológico , Vitamina K 1/administración & dosificación , Erupciones Acneiformes/inducido químicamente , Erupciones Acneiformes/diagnóstico , Erupciones Acneiformes/epidemiología , Administración Cutánea , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Erupciones por Medicamentos/diagnóstico , Erupciones por Medicamentos/epidemiología , Erupciones por Medicamentos/etiología , Receptores ErbB/antagonistas & inhibidores , Femenino , Humanos , Incidencia , Masculino , Índice de Severidad de la Enfermedad , Crema para la Piel/administración & dosificación , Resultado del TratamientoRESUMEN
Background: Acne-like skin rash is a frequently occurring adverse event associated with drugs against the epidermal growth factor receptor. This randomized vehicle-controlled study investigated the addition of vitamin K1 cream to doxycycline in patients with metastatic colorectal cancer treated with cetuximab. Patients and methods: Patients receiving first-line cetuximab + FOLFIRI were randomly assigned to prophylactic treatment with doxycylin and vitamin K1 cream or doxycycline and the vehicle. The primary end point of the study was the incidence of grade ≥ 2 skin rash (NCI CTCAE version 4.02) during 8 weeks of skin treatment. Secondary end points comprised skin rash according to a more thorough tripartite skin toxicity score (WoMo), quality of life, efficacy, and compliance. The study had 80% power to show a 20% reduction of the incidence of grade ≥ 2 skin rash. Results: A total of 126 patients were analyzed. The incidence of skin rash grade ≥ 2 was comparable between the arms. Likewise, no difference was seen in the WoMo score with respect to the percentage of skin affected. However, starting in week 5 and increasing over time patients treated with vitamin K1 cream had less severe rash and fewer fissures. Quality of life as well as efficacy and compliance with study medication and anticancer treatment was comparable in both arms. Conclusion: The primary end point of decreasing grade ≥ 2 skin rash was not met. However, using vitamin K1 cream as part of prophylactic treatment decreased the severity of acne-like skin rash according to WoMo, an alternative and more thorough skin toxicity scoring tool.
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Cetuximab/efectos adversos , Neoplasias Colorrectales/tratamiento farmacológico , Exantema/inducido químicamente , Exantema/prevención & control , Vehículos Farmacéuticos , Crema para la Piel , Vitamina K 1/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Camptotecina/administración & dosificación , Camptotecina/efectos adversos , Camptotecina/análogos & derivados , Neoplasias Colorrectales/patología , Método Doble Ciego , Doxiciclina/administración & dosificación , Exantema/fisiopatología , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Leucovorina/administración & dosificación , Leucovorina/efectos adversos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Cooperación del Paciente , Calidad de Vida , Adulto JovenRESUMEN
BACKGROUND: The aim of this study was to evaluate the impact of pathologic complete response (pCR) on outcome in patients with gastric or esophagogastric junction (EGJ) adenocarcinoma after neoadjuvant docetaxel/platin/fluoropyrimidine-based chemotherapy. PATIENTS AND METHODS: Patients received at least one cycle of chemotherapy for potentially operable disease. Pretreatment clinicopathologic factors and pCR were investigated. Disease-free survival (DFS), overall survival (OS) and tumor-related death were correlated with pCR. RESULTS: One hundred twenty patients were included in this analysis. Eighteen patients (15%) achieved a pCR. Tumor localization in the EGJ was identified as the only significant predictor of pCR (P = 0.019). Median follow-up was 41.1 months. Median DFS and OS for all patients were 24.1 and 48.6 months, respectively. Median DFS for patients with a pCR was not reached versus 22.1 months non-pCR patients (hazard ratio, HR 0.38; 3-year DFS: 71.8% and 37.7%, respectively, P = 0.018). While OS was not significantly different, the risk for tumor-related death was significantly lower for pCR patients compared with non-pCR patients (3-year cumulative incidences of 6.4% and 45.4%, respectively, P = 0.009). CONCLUSION: A pCR following preoperative docetaxel/platin/fluoropyrimidine indicates favorable outcome in patients with gastric or EGJ adenocarcinoma. Tumor location in the EGJ is associated with a higher pCR rate.
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Adenocarcinoma/tratamiento farmacológico , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Gástricas/tratamiento farmacológico , Taxoides/uso terapéutico , Adenocarcinoma/mortalidad , Adenocarcinoma/cirugía , Adulto , Anciano , Antimetabolitos Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Capecitabina , Quimioterapia Adyuvante , Cisplatino/uso terapéutico , Terapia Combinada , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapéutico , Supervivencia sin Enfermedad , Docetaxel , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/cirugía , Unión Esofagogástrica/efectos de los fármacos , Unión Esofagogástrica/patología , Unión Esofagogástrica/cirugía , Femenino , Fluorouracilo/análogos & derivados , Fluorouracilo/uso terapéutico , Humanos , Leucovorina/uso terapéutico , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia/tratamiento farmacológico , Compuestos Organoplatinos/uso terapéutico , Oxaliplatino , Inducción de Remisión , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/cirugía , Sobrevida , Tasa de Supervivencia , Complejo Vitamínico B/uso terapéuticoRESUMEN
BACKGROUND: The aim of this exploratory subgroup analysis of the fluorouracil, oxaliplatin, docetaxel (FLOT)65+ trial was to determine tolerability and feasibility of perioperative chemotherapy in elderly, potentially operable esophagogastric cancer patients. METHODS: Patients aged ≥65 with locally advanced esophagogastric adenocarcinoma were randomized to perioperative chemotherapy consisting of four pre- and four postoperative cycles of infusional 5-FU, leucovorin, and oxaliplatin (FLO) without or with docetaxel 50 mg m(-)(2) (FLOT), every 2 weeks. RESULTS: Forty-four patients with a median age of 70 years were randomized and 43 patients started preoperative chemotherapy (FLO, 22; FLOT, 21). Thirty-eight (86.4%) patients completed four cycles of preoperative chemotherapy and 32 (74.4%) proceeded to surgery, with 67.4% R0 resections on intent-to-treat analysis (90.1% of the 32 patients who underwent resection). Median overall survival was not reached and median progression-free survival (PFS) was 17.3 months. Compared with the FLO group, the FLOT group showed a trend towards an improved median PFS (21.1 vs 12.0 months; P=0.09), however, associated with increased chemotherapy related toxicity. No perioperative mortality was observed. Postoperative morbidity was observed in 46.9% of patients (FLO, 35.3%; FLOT, 60%). CONCLUSION: Neoadjuvant FLO or FLOT may offer a reasonable chance of curative surgery in elderly patients with locally advanced resectable gastroesophageal cancer. However, the increase in side effects with the FLOT regimen and postoperative morbidity should be carefully considered when an intensive chemotherapy regimen is planned.
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Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Gástricas/tratamiento farmacológico , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Anciano , Docetaxel , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Estudios de Factibilidad , Femenino , Fluorouracilo/administración & dosificación , Estudios de Seguimiento , Humanos , Leucovorina/administración & dosificación , Masculino , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Atención Perioperativa , Pronóstico , Estudios Prospectivos , Calidad de Vida , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Tasa de Supervivencia , Taxoides/administración & dosificaciónRESUMEN
BACKGROUND: The prognostic role of matrix metalloproteinase-9 (MMP-9) in metastatic gastric cancer has not been validated. PATIENTS AND METHODS: We carried out a molecular analysis in 222 metastatic gastric cancer patients obtained from clinical trials. We assessed the messenger RNA (mRNA) expression of MMP-9, vascular endothelial growth factor receptor-A, and epidermal growth factor receptor in a training cohort of 130 patients and conducted an independent validation in 92 patients. Automated RNA extraction from paraffin and RT-quantitative PCR was used. Immunohistochemistry for MMP-9 and diverse immune cell infiltrates was conducted. RESULTS: In the training cohort, only MMP-9 significantly correlated with patient's survival. At the cut-off with the highest predictive value, 19% of patients had MMP-9 expression above this cut-off and these showed a median survival of 3.6 months compared with 10.5 months (P=1.7e(-6)) in patients with lower expression. Corresponding 1- and 2-year survivals were 9% and 44% and 0 and 21%, respectively. The application of this cut-off to the validation cohort revealed similar distributions of overall survival according to MMP-9 expression on uni- (P<0.001) and multivariate analyses (P<0.001). No differences in survival according to MMP-9 below best cut-off were found. MMP-9 protein assessed by immunohistochemistry was not prognostic. CONCLUSION: MMP-9 mRNA expression above a certain cut-off level is associated with dismal survival.
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Adenocarcinoma/enzimología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Expresión Génica , Metaloproteinasa 9 de la Matriz/genética , Neoplasias Gástricas/enzimología , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/mortalidad , Adenocarcinoma/secundario , Adulto , Anciano , Anciano de 80 o más Años , Cisplatino/administración & dosificación , Ensayos Clínicos Fase III como Asunto , Docetaxel , Receptores ErbB/genética , Receptores ErbB/metabolismo , Femenino , Fluorouracilo/administración & dosificación , Humanos , Estimación de Kaplan-Meier , Leucovorina/administración & dosificación , Masculino , Metaloproteinasa 9 de la Matriz/metabolismo , Persona de Mediana Edad , Análisis Multivariante , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Pronóstico , Modelos de Riesgos Proporcionales , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Taxoides/administración & dosificación , Resultado del Tratamiento , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
AIMS: Alcohol, tobacco smoke and Barrett's oesophagus as a consequence of gastro-oesophageal reflux are the main risk factors in oesophageal carcinogenesis. All risk factors may induce oxidative stress. Manganese superoxide dismutase (MnSOD) is one important repair enzyme for reactive oxidative stress (ROS)-induced damage. MnSOD polymorphisms in the -9 position of the signal sequence of the protein may lead to critical enzyme deficiency. The aim of the present study was to investigate the role of polymorphisms of MnSOD in patients with oesophageal cancer [n = 170, 61 patients with adenocarcinoma (AC), 109 patients with squamous cell carcinoma (SCC)] compared to heavy drinkers (n = 160) and healthy blood donors (n = 400). METHODS: Genotyping was performed by PCR-RFLP analysis using genomic DNA extracted from whole blood. RESULTS: The Ala/Ala genotype was 27.7% in cancer patients (29.5% AC, 26.6% SCC), 23.1% in patients with heavy alcohol abuse and 12.5% in the group of healthy blood donors. These results were not statistically significant after multivariate analysis controlling for age, sex, alcohol, cigarettes and interactions (odds ratio 0.92, 95% confidence interval = 0.63-1.36, for cancer patients versus heavy drinkers; odds ratio 1.02, 95% confidence interval = 0.51-2.03, for cancer patients versus blood donors; analysis by logistic regression). Subjects with an Ala/Ala genotype (81.3 g/day) had a significantly higher alcohol intake than those with Val/Ala (63.9 g/day) or Val/Val (53.8 g/day) genotype (P < 0.00001 by the Kruskal-Wallis test). CONCLUSIONS: MnSOD polymorphisms play no role in the genetic predisposition to oesophageal cancer. However, our data suggest a complex gene-to-phenotype interaction between the MnSOD genotype and alcohol misuse.
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Adenocarcinoma/epidemiología , Adenocarcinoma/genética , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/epidemiología , Neoplasias Esofágicas/genética , Etanol/efectos adversos , Fumar/efectos adversos , Superóxido Dismutasa/genética , Anciano , Estudios de Cohortes , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo Genético/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de RiesgoRESUMEN
BACKGROUND: In severe steroid-refractory Crohn's disease (CD), established therapies fail in a relevant proportion of patients. Recent pilot studies indicated the efficacy of cyclophosphamide pulse therapy in these patients. AIM: To provide further and substantial evidence for the rationale to apply cyclophosphamide pulse therapy as therapeutic option in severe courses of CD. METHODS: Fifteen patients with steroid-refractory (n = 13) or steroid-dependent (n = 2) CD received 2-6 (median 3) monthly pulses of 750 mg cyclophosphamide in an open-label fashion. Eleven patients were on concomitant immunosuppression (azathioprine/mercaptopurine n = 9; methotrexate n = 2). RESULTS: Thirteen of 15 patients (87%) had a clinical response (CDAI decrease >100). Ten patients (67%) went into remission (CDAI <150) after 8 weeks. Steroid-free remission was achieved in eight patients (54%). Two patients (13%) failed to respond. Median CDAI decreased from 420 (245-550) to 100 (26-538) at week 8. Remission lasted 16 months (median, range 4-40). In three patients, arthritis, erythema nodosum and episcleritis completely resolved. Cyclophosphamide pulse therapy administration was well tolerated in all subjects. CONCLUSIONS: Cyclophosphamide pulse therapy is safe and highly effective for induction and maintenance of remission in steroid-refractory/-dependent CD. There is a strong need for additional experience to improve the setting of the encouraging cyclophosphamide treatment in CD.
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Enfermedad de Crohn/tratamiento farmacológico , Ciclofosfamida/administración & dosificación , Inmunosupresores/administración & dosificación , Adulto , Anciano , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Quimioterapia por Pulso , Inducción de Remisión , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Recent studies suggested p53 mutations as a prognostic factor. Tumors of the esophagus and gastroesophageal (GE) junction show raising incidence with a general poor prognosis. METHODS: p53 Mutational spectra in 103 patients (68 squamous cell carcinoma/SCC and 35 adenocarcinoma/AC) were compared to clinical and pathologic data. RESULTS AND CONCLUSIONS: p53 Mutations were found in 26 of 68 SSC (38.2%) and in 12 of 35 AC (34.5%). We only found G > T transversions in smokers with SCC. The survival of patients was not affected by p53 mutational status. In our study, the frequency and mutational spectrum of mutant p53 is similar in both histological types without prognostic relevance.
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Adenocarcinoma/genética , Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Unión Esofagogástrica/patología , Mutación/genética , Proteína p53 Supresora de Tumor/genética , Adenocarcinoma/patología , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/patología , Estudios de Cohortes , Análisis Mutacional de ADN , ADN de Neoplasias/genética , Neoplasias Esofágicas/patología , Unión Esofagogástrica/metabolismo , Esófago/metabolismo , Esófago/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Reacción en Cadena de la Polimerasa , Pronóstico , Fumar , Tasa de SupervivenciaRESUMEN
BACKGROUND: The combination of docetaxel (Taxotere), cisplatin, and fluorouracil improved efficacy in gastric cancer, but was associated with substantial toxicity. This study was designed to incorporate docetaxel into a tolerable biweekly (once every 2 weeks) oxaliplatin-based chemotherapy regimen. PATIENTS AND METHODS: Patients with measurable, metastatic adenocarcinoma of the stomach or esophagogastric junction and no prior chemotherapy received oxaliplatin 85 mg/m(2), leucovorin 200 mg/m(2), and fluorouracil 2600 mg/m(2) as a 24-h infusion in combination with docetaxel 50 mg/m(2) (FLOT) on day 1 every 2 weeks. Prophylactic growth factors were not administered. RESULTS: Fifty-nine patients were enrolled; 54 received treatment. Patients had a median age of 60 years (range 29-76) and most (93%) of them had metastatic disease. Objective responses were observed in 57.7% of patients with a median time to treatment response of 1.54 months. Median progression-free survival (PFS) and overall survival were 5.2 and 11.1 months, respectively. Twenty-five percent of patients experienced prolonged (>12 months) PFS. Frequent (>10%) grade 3 or 4 toxic effects included neutropenia in 26 (48.1%), leukopenia in 15 (27.8%), diarrhea in 8 (14.8%), and fatigue in 6 (11.1%) patients. Complicated neutropenia was observed in two (3.8%) patients, only. CONCLUSIONS: Biweekly FLOT is active and has a favorable safety profile.
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Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias Esofágicas/tratamiento farmacológico , Unión Esofagogástrica/patología , Neoplasias Gástricas/tratamiento farmacológico , Adenocarcinoma/patología , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Supervivencia sin Enfermedad , Docetaxel , Esquema de Medicación , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Leucovorina/administración & dosificación , Leucovorina/efectos adversos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/efectos adversos , Oxaliplatino , Neoplasias Gástricas/patología , Taxoides/administración & dosificación , Taxoides/efectos adversosRESUMEN
BACKGROUND: Psychosocial factors play an important role in the course of inflammatory bowel disease (IBD). However, a simple, valid psychosocial screening instrument that is suitable for short patient-physician contacts does not exist. Therefore, the Luebeck semistructured Interview for Psychosocial Screening was developed as a rating tool for psychosocial stress in IBD patients (LIPS-IBD). METHOD: The entire interview requires approximately 10 minutes. Interrater reliability was tested. Depression, anxiety, social support, impact of the disease, global level of psychosocial stress, and demand for psychosocial support were rated in 92 patients with IBD on 5 point Likert scales. Patients from the in- and out-patient clinic for gastroenterology were included. In addition, patients filled out self-report questionnaires regarding depression, anxiety, social support, and impact of the disease. Indices of disease activity (Colitis Activity Index, Crohn's Disease Activity Index) were recorded. RESULTS: Both patients and physicians found the interview feasible. Reliability was good, with interrater reliability ranging from .76 to .94. Convergence with self-report instruments was also high (r = .5-.6). Ratings of depression and impact of the disease were correlated with indices of disease activity. DISCUSSION: LIPS helps to identify patients with high levels of psychosocial stress and provide them with more detailed psychologic assessments. It was found to be a suitable instrument for daily clinical routine. It is potentially a valuable screening tool to obtain reliable, valid, and useful information in daily practice in IBD treatment settings.
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Enfermedades Inflamatorias del Intestino/psicología , Entrevista Psicológica , Adulto , Ansiedad/diagnóstico , Ansiedad/etiología , Depresión/diagnóstico , Depresión/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Reproducibilidad de los Resultados , Perfil de Impacto de Enfermedad , Apoyo Social , Estrés Psicológico/diagnóstico , Estrés Psicológico/etiologíaRESUMEN
BACKGROUND: The use of intermittent compression devices for thrombosis prophylaxis and the reduction of postoperative swelling are widely accepted. The recommended minimum application of 2 h daily has never been statistically verified. Without evidence based data, the benefit of this costly equipment cannot be maximized. PATIENTS AND METHODS: A randomized clinical trial on 41 patients after total hip replacement was performed. The A-V Impulse System was applied for 2 h a day during the first 5 postoperative days to observe whether this time was sufficiently effective. RESULTS: In the control group, two deep vein thromboses occurred postoperatively, but there were none in the treatment group. Even though two patients from the treatment group had to be excluded from the study because of severe pain, all other parameters including visual analogue pain scale results and limb circumferences were comparable in both groups. CONCLUSION: These preliminary results suggest that pump systems can prevent deep venous thrombosis after hip surgery even when applied for only short intervals over a short period of time. However, large scale confirmatory studies are needed.
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Artroplastia de Reemplazo de Cadera , Inflamación/prevención & control , Aparatos de Compresión Neumática Intermitente , Complicaciones Posoperatorias/prevención & control , Trombosis/prevención & control , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Inflamación/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Proyectos Piloto , Complicaciones Posoperatorias/diagnóstico por imagen , Trombosis/diagnóstico por imagen , Factores de Tiempo , Resultado del Tratamiento , UltrasonografíaAsunto(s)
Transformación Celular Neoplásica/genética , Etanol/toxicidad , Neoplasias/genética , Alcohol Deshidrogenasa/genética , Aldehído Deshidrogenasa/genética , Animales , Bacterias/metabolismo , Neoplasias de la Mama/genética , Pruebas de Carcinogenicidad , Etanol/metabolismo , Neoplasias Gastrointestinales/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Predisposición Genética a la Enfermedad/genética , Humanos , Inactivación Metabólica/genética , Polimorfismo Genético/genética , Ratas , Tretinoina/farmacologíaRESUMEN
A 60-year-old woman with alcoholic cirrhosis of the liver was admitted to the ICU because of haemodynamic instability, hematemesis and presumed acute variceal bleeding. An upper endoscopy was performed and varices of the distal esophagus and an actively bleeding varix of the gastric fundus were detected. The bleeding was successfully treated with 2 consecutive injections of 0.5 ml n-butyl-2-cyanoacrylate and 0.5 ml lipiodol. The patient was intubated prior to the endoscopy to avoid blood aspiration. However, severe hypoxaemia with a need for prolonged mechanical ventilation and signs of right heart strain developed after endoscopy. A chest X-ray and CT scan of the thorax documented an extensive embolisation of the pulmonary arteries. The patient's varices were retreated with band ligation but rebleeding occurred. Finally, a TIPS application was needed to stop recurrent haemorrhage. This case demonstrates that embolisation of the pulmonary arterial bed is a rare complication of endoscopic sclerotherapy for gastric variceal bleeding. The severity of this complication may depend on the volume of liquid acrylate being injected and pre-existing lung tissue alterations. Since histoacryl is not lysable, severe pulmonary emboli with lung tissue damage and pulmonary hypertension may occur. Factors contributing to this complication are analysed and therapeutic alternatives are discussed.
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Endoscopía Gastrointestinal/efectos adversos , Várices Esofágicas y Gástricas/cirugía , Hemorragia Gastrointestinal/cirugía , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/etiología , Escleroterapia/efectos adversos , Endoscopía Gastrointestinal/métodos , Femenino , Humanos , Persona de Mediana Edad , Escleroterapia/métodosRESUMEN
BACKGROUND: Chronic ethanol consumption is associated with an increased risk of upper aerodigestive tract cancer. As acetaldehyde seems to be a carcinogenic factor associated with chronic alcohol consumption, alcoholics with the alcohol dehydrogenase (ADH) 1C*1 allele seem to be particularly at risk as this allele encodes for a rapidly ethanol metabolising enzyme leading to increased acetaldehyde levels. Recent epidemiological studies resulted in contradictory results and therefore we have investigated ADH1C genotypes in heavy alcohol consumers only. METHODS: We analysed the ADH1C genotype in 107 heavy drinkers with upper aerodigestive tract cancer and in 103 age matched alcoholic controls without cancer who consumed similar amounts of alcohol. Genotyping of the ADH1C locus was performed using polymerase chain reaction based on restriction fragment length polymorphism methods on leucocyte DNA. In addition, ethanol was administered orally (0.3 g/kg body weight) to 21 healthy volunteers with the ADH1C*1,1, ADH1C*1,2, and ADH1C*2,2 genotypes, and 12 volunteers with various ADH genotypes consumed ethanol ad libitum (mean 211 (29) g). Subsequently, salivary acetaldehyde concentrations were measured by gas chromatography or high performance liquid chromatography. RESULTS: The allele frequency of the ADH1C*1 allele was found to be significantly increased in heavy drinkers with upper aerodigestive tract cancer compared with age matched alcoholic controls without cancer (61.7% v 49.0%; p = 0.011). The unadjusted and adjusted odds ratios for all cancer cases versus all alcoholic controls were 1.67 and 1.69, respectively. Healthy volunteers homozygous for the ADH1C*1 allele had higher salivary acetaldehyde concentrations following alcohol ingestion than volunteers heterozygous for ADH1C (p = 0.056) or homozygous for ADH1C*2 (p = 0.011). CONCLUSIONS: These data demonstrate that heavy drinkers homozygous for the ADH1C*1 allele have a predisposition to develop upper aerodigestive tract cancer, possibly due to elevated salivary acetaldehyde levels following alcohol consumption.
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Acetaldehído/efectos adversos , Alcohol Deshidrogenasa/genética , Alcoholismo/genética , Neoplasias Laríngeas/genética , Neoplasias de la Boca/genética , Acetaldehído/metabolismo , Etanol/farmacología , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Neoplasias Laríngeas/metabolismo , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/metabolismo , Factores de Riesgo , Saliva/metabolismoAsunto(s)
Colitis Ulcerosa/complicaciones , Neoplasias del Colon/diagnóstico por imagen , Neoplasias de la Vesícula Biliar/diagnóstico por imagen , Adenocarcinoma/diagnóstico por imagen , Adulto , Colangiocarcinoma/diagnóstico por imagen , Colangitis Esclerosante/complicaciones , Neoplasias del Colon/etiología , Neoplasias del Colon/cirugía , Neoplasias de la Vesícula Biliar/etiología , Neoplasias de la Vesícula Biliar/cirugía , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Masculino , Neoplasias Primarias Múltiples/diagnóstico por imagen , UltrasonografíaAsunto(s)
Linfangiectasia Intestinal/tratamiento farmacológico , Octreótido/administración & dosificación , Adulto , Velocidad del Flujo Sanguíneo/efectos de los fármacos , Velocidad del Flujo Sanguíneo/fisiología , Preparaciones de Acción Retardada , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Humanos , Inyecciones Intramusculares , Linfangiectasia Intestinal/diagnóstico por imagen , Arterias Mesentéricas/diagnóstico por imagen , Prevención Secundaria , Ultrasonografía DopplerRESUMEN
The aim of the study was to evaluate and compare health-related quality of life (HR-QoL) and depression in essential blepharospasm (BSP) and idiopathic cervical dystonia (CD), to identify the clinical and demographic factors associated with poor HR-QoL in both disorders and to analyse the effect of Botulinum Toxin A (BtxA) therapy. Two hundred-twenty consecutive patients with BSP (N = 89, 62 % women, mean age 64 years, mean disease duration 7 years) and CD (N = 131, 64 % women, mean age 53 years, mean disease duration 8 years) recruited from routine referrals to eight Austrian dystonia clinics were included. HR-QoL was measured by the Short Form 36 (SF-36) and depression by the Beck Depression Inventory (BDI). At baseline, patients with CD and BSP scored significantly worse in all eight SF-36 domains compared with an age-matched community sample. In addition, 47 % of patients with CD and 37 % of those with BSP were depressed. Women with BSP scored significantly lower in all SF-36 domains and were more depressed than male patients. In contrast, there was no significant effect of gender on HR-QoL and depression in CD. Neck pain had a significant impact on all SF-36 domains and represented the main determinant of depression in CD. Although BtxA therapy resulted in a significant improvement of clinical symptoms in BSP and CD, HR-QoL did not improve in BSP and only two of the eight SF-36 domains improved significantly in patients with CD. The present study for the first time demonstrated that BSP has a substantial impact on health status emphasizing the need for psychological support with interventions aimed at treating depression in these patients. Our results provide further evidence for the profound impact of CD on HR-QoL and indicate the importance of an adequate management of neck pain in addition to reducing the severity of dystonia in CD. The mismatch between objective BtxA derived improvement of dystonia and lack of change of HR-QoL as determined by the SF-36 illustrates the need for optimized disease specific quality of life rating scales in patients with craniocervical dystonia.
Asunto(s)
Blefaroespasmo/psicología , Depresión/etiología , Calidad de Vida , Tortícolis/psicología , Anciano , Blefaroespasmo/complicaciones , Blefaroespasmo/tratamiento farmacológico , Toxinas Botulínicas Tipo A/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fármacos Neuromusculares/uso terapéutico , Índice de Severidad de la Enfermedad , Factores Sexuales , Tortícolis/complicaciones , Tortícolis/tratamiento farmacológico , Resultado del TratamientoRESUMEN
Scars around the neural structures after opening the spinal canal are common and severe problems in spine surgery. This paper presents the use of a special membrane to avoid epidural scarring in two cases.