RESUMEN
Achalasia is a relatively rare primary motor esophageal disorder, characterized by absence of relaxations of the lower esophageal sphincter and of peristalsis along the esophageal body. As a result, patients typically present with dysphagia, regurgitation and occasionally chest pain, pulmonary complication and malnutrition. New diagnostic methodologies and therapeutic techniques have been recently added to the armamentarium for treating achalasia. With the aim to offer clinicians and patients an up-to-date framework for making informed decisions on the management of this disease, the International Society for Diseases of the Esophagus Guidelines proposed and endorsed the Esophageal Achalasia Guidelines (I-GOAL). The guidelines were prepared according the Appraisal of Guidelines for Research and Evaluation (AGREE-REX) tool, accredited for guideline production by NICE UK. A systematic literature search was performed and the quality of evidence and the strength of recommendations were graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Given the relative rarity of this disease and the paucity of high-level evidence in the literature, this process was integrated with a three-step process of anonymous voting on each statement (DELPHI). Only statements with an approval rate >80% were accepted in the guidelines. Fifty-one experts from 11 countries and 3 representatives from patient support associations participated to the preparations of the guidelines. These guidelines deal specifically with the following achalasia issues: Diagnostic workup, Definition of the disease, Severity of presentation, Medical treatment, Botulinum Toxin injection, Pneumatic dilatation, POEM, Other endoscopic treatments, Laparoscopic myotomy, Definition of recurrence, Follow up and risk of cancer, Management of end stage achalasia, Treatment options for failure, Achalasia in children, Achalasia secondary to Chagas' disease.
Asunto(s)
Acalasia del Esófago/diagnóstico , Acalasia del Esófago/terapia , Adulto , Toxinas Botulínicas/uso terapéutico , Niño , Dilatación/métodos , Dilatación/normas , Manejo de la Enfermedad , Acalasia del Esófago/fisiopatología , Esofagoscopía/métodos , Esofagoscopía/normas , Medicina Basada en la Evidencia , Femenino , Humanos , Masculino , Miotomía/métodos , Miotomía/normas , Factores de Riesgo , Índice de Severidad de la Enfermedad , Evaluación de Síntomas/métodos , Evaluación de Síntomas/normasAsunto(s)
Infección Hospitalaria/diagnóstico , Neumonía Bacteriana/diagnóstico , Respiración Artificial/efectos adversos , Líquido del Lavado Bronquioalveolar , Cuidados Críticos/métodos , Infección Hospitalaria/etiología , Infección Hospitalaria/microbiología , Humanos , Neumonía Bacteriana/etiología , Neumonía Bacteriana/microbiologíaRESUMEN
The intestinal mucosa is an active participant in the inflammatory and metabolic response to sepsis, endotoxemia, and other critical illness. The genes for various cytokines, e.g., interleukin 6 (IL-6), are regulated by multiple transcription factors, including nuclear factor-kappa B (NF-kappaB) and activator protein-1 (AP-1). In recent studies, treatment with IL-1beta of cultured Caco-2 cells, a human intestinal epithelial cell line, resulted in increased NF-kappaB DNA binding. The effect of IL-1beta on AP-1 activity in the enterocyte and the potential role of AP-1 in enterocyte IL-6 production are not known. We treated Caco-2 cells with IL-1beta and determined AP-1 activity by electrophoretic mobility shift assay (EMSA) and IL-6 production by enzyme-linked immunosorbent assay (ELISA). Treatment of Caco-2 cells with IL-1beta resulted in a dose- and time-dependent increase in AP-1 DNA binding. Supershift analysis suggests that activated AP-1 contained c-Jun, JunD, c-Fos, FosB, and Fra1 subunits. When Caco-2 cells were transiently transfected with an AP-1 luciferase reporter plasmid, stimulation with IL-1beta resulted in increased luciferase activity, suggesting that AP-1 DNA binding increased gene activation. Additional luciferase assays were performed with a plasmid containing a wild-type or AP-1-mutated IL-6 promoter. Stimulation of these cells with IL-1beta gave rise to results supporting the role of AP-1 in the regulation of IL-6 production. Geldanamycin, which has been shown in studies to inhibit AP-1 activation, blocked IL-1beta-induced AP-1 luciferase gene activation and IL-6 production. These results suggest that the AP-1 family of transcription factors is activated by IL-1beta in human enterocytes and that AP-1 may at least in part regulate IL-6 production in these cells.
Asunto(s)
Enterocitos/metabolismo , Interleucina-1/farmacología , Interleucina-6/metabolismo , Factor de Transcripción AP-1/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Benzoquinonas , ADN/metabolismo , Enterocitos/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Humanos , Interleucina-6/genética , Lactamas Macrocíclicas , Regiones Promotoras Genéticas , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas c-fos/genética , Proteínas Proto-Oncogénicas c-fos/metabolismo , Quinonas/farmacología , Proteínas Recombinantes/efectos de los fármacos , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Factor de Transcripción AP-1/efectos de los fármacos , Factor de Transcripción AP-1/genética , Transfección , Células Tumorales CultivadasRESUMEN
BACKGROUND: Bilateral synchronous breast cancer is uncommon (accounting for 1.0%-2.6% of all patients with breast cancer), and most physicians do not accumulate a large personal experience of patients with this disease. We reviewed our experience with patients with bilateral synchronous breast cancer, focusing on the mode of detection and histologic features in the 2 breasts. METHODS: The charts of patients who were treated at this institution for bilateral synchronous breast cancer during the 15-year period of 1984 through 1999 were reviewed. Information regarding age, mode of detection, histopathologic features, treatment, and overall survival were analyzed. RESULTS: During the study period, 51 patients (all women) were treated at our institution for bilateral synchronous breast cancer. This comprised 2.1% of all patients (n = 2382 patients) treated for breast cancer during the same period of time. The first cancer was detected by palpation in 81% and by mammography in 14%. The corresponding figures for the contralateral cancer were 24% and 54%, respectively. The histologic type of cancer was identical in the 2 breasts in 29 patients (57%) and was different between the 2 breasts in 22 patients (43%). The overall 10-year survival rate was 63%. CONCLUSIONS: Bilateral synchronous breast cancer is often detected by mammography and is frequently of the same histologic type as the index cancer. A better awareness of the risk for this disease may help detect bilateral breast cancer earlier.
Asunto(s)
Neoplasias de la Mama/patología , Mama/patología , Carcinoma Ductal de Mama/patología , Carcinoma Lobular/patología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/mortalidad , Carcinoma in Situ/diagnóstico por imagen , Carcinoma in Situ/mortalidad , Carcinoma in Situ/patología , Carcinoma Ductal de Mama/diagnóstico por imagen , Carcinoma Ductal de Mama/mortalidad , Carcinoma Lobular/diagnóstico por imagen , Carcinoma Lobular/mortalidad , Femenino , Humanos , Incidencia , Mamografía , Persona de Mediana Edad , Palpación , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
The transcription nuclear factor-kappaB (NF-kappaB) regulates a large number of genes involved in the inflammatory response to sepsis and endotoxemia. We recently found that NF-kappaB is activated in the jejunal mucosa during endotoxemia, but the response of NF-kappaB in other parts of the gastrointestinal tract is not known. We hypothesized that NF-kappaB is differentially activated in different regions of the gastrointestinal tract during endotoxemia. NF-kappaB DNA binding activity was determined by electrophoretic mobility shift assay in mucosa of the stomach, jejunum, ileum, and colon from endotoxemic and saline-injected mice. Cytoplasmic levels of the NF-kappaB inhibitory proteins IkappaB-alpha and IkappaB-beta were determined by Western blot analysis. Endotoxemia increased NF-kappaB activity in mucosa of stomach, jejunum, and ileum, with jejunum responding to smaller doses of endotoxin than the other parts of the gastrointestinal tract. NF-kappaB DNA binding activity was not induced in colonic mucosa, even following administration of high doses of endotoxin. IkappaB-alpha and IkappaB-beta levels decreased in jejunal mucosa of endotoxin injected mice, concomitant with activation of NF-kappaB. The results suggest that during endotoxemia, NF-kappaB is activated in mucosa of stomach and small intestine, but not in colon, and that the jejunum is particularly sensitive to endotoxin.