RESUMEN
OBJECTIVES: Arbaclofen placarbil (AP), previously designated as XP19986, is an investigational prodrug of the active R-isomer of baclofen, a gamma-aminobutyric acid agonist reflux inhibitor. The aim of this study was to assess the efficacy and safety of AP for decreasing meal-induced reflux episodes in patients with gastroesophageal reflux disease (GERD). METHODS: We conducted a multicenter, randomized, double-blind, crossover study comparing single doses of AP with placebo. Different patients were enrolled at each of four escalating AP doses: 10, 20, 40, and 60 mg. Enrolled patients had GERD symptoms at least three times a week and 20 reflux episodes on impedance/pH monitoring over a period of 2 h. During study visits separated by periods of 3-7 days, patients received single doses of AP or placebo, followed by high-fat meals 2 and 6 h after treatment. The primary end point was the number of reflux episodes over 12 h after treatment. RESULTS: A total of 50 patients were treated; efficacy analysis included 44 patients who received both AP and placebo and had technically satisfactory impedance/pH data. For the combined data from all dose cohorts, there was a statistically significant (P=0.01) decrease in reflux episodes over 12 h after treatment with AP compared with placebo. The mean (s.d.) number of reflux episodes over 12 h after AP treatment was 50.5 (27.2), with a mean reduction of 10.4 (23.9) episodes (17%) compared with placebo, for which a mean (s.d.) number of 60.9 (35.3) episodes was observed. Heartburn events associated with reflux were reduced during treatment with AP compared with placebo. AP seemed to be the most efficacious in the 60-mg dose group, and was well tolerated at all dose levels. CONCLUSIONS: AP decreased reflux and associated symptoms with good tolerability in patients with GERD.
Asunto(s)
Reflujo Gastroesofágico/tratamiento farmacológico , Fármacos Gastrointestinales/uso terapéutico , Profármacos/uso terapéutico , Adulto , Baclofeno/análogos & derivados , Estudios Cruzados , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Monitorización del pH Esofágico , Femenino , Pirosis/tratamiento farmacológico , Humanos , Masculino , Manometría , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: Attention has focused on whether normalization, regression, and development of dysplasia and cancer in specialized intestinal metaplasia (SIM) differ among long-segment Barrett's esophagus (LSBE), short-segment BE (SSBE), and esophagogastric junction SIM (EGJSIM). We prospectively followed a cohort of SIM patients receiving long-term antisecretory medications to determine: (a) histologic normalization (no evidence of SIM on biopsy), (b) change in SIM length, (c) incidence of dysplasia and cancer, and (d) factors associated with normalization. METHODS: One hundred forty-eight patients with SIM were identified in our original cohort. Of these, 60.5% (23/38) LSBE, 69.8% (44/63) SSBE, and 72.3% (34/47) EGJSIM patients underwent repeat surveillance over a mean 44.4 +/- 9.7 months. Demographic, clinical, and endoscopic data were obtained. RESULTS: (a) With long-term, antisecretory therapy, normalization occurred in 0/23 LSBE, 30% (13/44) of SSBE, and 68% (23/34) of EGJSIM (P < 0.001). (b) Normalization was more likely with EGJSIM (odds ratio [OR] 6.7, CI 2.3-19.3, P= 0.005), female gender (OR 7.3, CI 2.3-23.1, P= 0.001), or absence of hiatal hernia (OR 2.9, CI 1.02-8.06, P= 0.002). (c) A significant decrease in mean SIM length was noted for the entire population (2.5 +/- 0.3 to 2.13 +/- 0.3 cm, P= 0.004). (d) Follow-up incidence of dysplasia and cancer was 26.1% (3 indefinite, 2 low-grade dysplasia [LGD], 1 cancer) for LSBE, 6.8% (2 indefinite, 1 LGD) for SSBE, and none for EGJSIM (P < 0.004). CONCLUSIONS: (a) Normalization of SIM occurs most frequently in EGJSIM>SSBE>LSBE. (b) Factors associated with normalization favor less severe GER and shorter segments of SIM. (c) Surveillance of LSBE results in the greatest yield for identifying dysplasia and cancer.
Asunto(s)
Neoplasias Esofágicas/epidemiología , Unión Esofagogástrica/patología , Neoplasias Gástricas/epidemiología , Anciano , Biopsia , Progresión de la Enfermedad , Endoscopía Gastrointestinal , Neoplasias Esofágicas/patología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Metaplasia/epidemiología , Metaplasia/patología , Persona de Mediana Edad , Prevalencia , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Neoplasias Gástricas/patología , Estados Unidos/epidemiologíaAsunto(s)
Enfermedades del Colon/diagnóstico , Enfermedades del Colon/cirugía , Endoscopía Gastrointestinal , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/cirugía , Colonoscopía , Humanos , Tracto Gastrointestinal Inferior/patología , Tracto Gastrointestinal Inferior/cirugíaAsunto(s)
Enfermedades de las Vías Biliares , Colangiopancreatografia Retrógrada Endoscópica/normas , Gastroenterología , Enfermedades Pancreáticas , Sociedades Médicas , Enfermedades de las Vías Biliares/diagnóstico , Enfermedades de las Vías Biliares/cirugía , Humanos , Enfermedades Pancreáticas/diagnóstico , Enfermedades Pancreáticas/cirugíaAsunto(s)
Estreñimiento/diagnóstico , Estreñimiento/terapia , Endoscopía Gastrointestinal , Colonoscopía , Femenino , Humanos , MasculinoRESUMEN
Two patients with previously normal liver function, who presented with fulminant hepatic failure (FHF) of unknown etiology despite an extensive evaluation, are described. No etiology for FHF was apparent with initial evaluation. One patient was found to have nearly complete replacement of hepatic parenchyma by metastasis from an occult small cell lung carcinoma identified postmortem. The other patient had lymphomatous infiltration of the liver detected by a liver biopsy. Imaging studies were performed in the patients and did not reveal any evidence of neoplastic infiltration of the liver. Neoplastic involvement of liver should be considered in the differential diagnosis of FHF of unknown etiology. The imaging studies in this setting can be misleading.
Asunto(s)
Carcinoma de Células Pequeñas/complicaciones , Fallo Hepático Agudo/etiología , Neoplasias Hepáticas/complicaciones , Neoplasias Pulmonares/patología , Linfoma/patología , Anciano , Biopsia , Carcinoma de Células Pequeñas/secundario , Diagnóstico Diferencial , Resultado Fatal , Humanos , Fallo Hepático Agudo/diagnóstico por imagen , Fallo Hepático Agudo/patología , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Radiografía Abdominal , Tomografía Computarizada por Rayos XRESUMEN
This is one of a series of statements discussing the utilization of GI endoscopy in common clinical situations. The Standards of Practice Committee of the American Society for Gastrointestinal Endoscopy prepared this text. In preparing this guideline, a MEDLINE literature search was performed, and additional references were obtained from the bibliographies of the identified articles and from recommendations of expert consultants. When little or no data exist from well-designed prospective trials, emphasis is given to results from large series and reports from recognized experts. Guidelines for appropriate use of endoscopy are based on a critical review of the available data and expert consensus. Further controlled clinical studies are needed to clarify aspects of this statement, and revision may be necessary as new data appear. Clinical consideration may justify a course of action at variance to these recommendations.
Asunto(s)
Endoscopía Gastrointestinal , Heparina de Bajo-Peso-Molecular/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Ensayos Clínicos como Asunto , HumanosRESUMEN
This is one of a series of statements discussing the utilization of GI endoscopy in common clinical situations. The Standards of Practice Committee of the American Society for Gastrointestinal Endoscopy prepared this text. In preparing this guideline, a MEDLINE literature search was performed, and additional references were obtained from the bibliographies of the identified articles and from recommendations of experts. When little or no data exist from well-designed prospective trials, emphasis is given to results from large series and reports from recognized experts. Guidelines for appropriate utilization of endoscopy are based on a critical review of the available data and expert consensus. Further controlled clinical studies are needed to clarify aspects of this statement and revision needed to clarify aspects of this statement and revision may be necessary as new data appear. Clinical consideration may justify a course of action at variance to the recommendations.
Asunto(s)
Neoplasias del Colon/patología , Neoplasias del Colon/cirugía , Colonoscopía/normas , Neoplasias del Recto/patología , Neoplasias del Recto/cirugía , Biopsia con Aguja , Pólipos del Colon/patología , Pólipos del Colon/cirugía , Humanos , Estadificación de NeoplasiasRESUMEN
This is one of a series of statements discussing the utilization of GI endoscopy in common clinical situations. The Standards of Practice Committee of the American Society for Gastrointestinal Endoscopy prepared this text. In preparing this guideline, a MEDLINE literature search was performed, and additional references were obtained from the bibliographies of the identified articles and from recommendations of experts. When little or no data exist from well-designed prospective trials, emphasis is given to results from large series and reports from recognized experts. Guidelines for appropriate utilization of endoscopy are based on a critical review of the available data and expert consensus. Further controlled clinical studies are needed to clarify aspects of this statement and revision needed to clarify aspects of this statement and revision may be necessary as new data appear. Clinical consideration may justify a course of action at variance to the recommendations.
Asunto(s)
Endosonografía/efectos adversos , Bloqueo Nervioso Autónomo/efectos adversos , Bacteriemia/etiología , Biopsia con Aguja Fina/efectos adversos , Plexo Celíaco/cirugía , Hemorragia Gastrointestinal/etiología , Humanos , Pancreatitis/etiología , Peritonitis/etiología , Hemorragia Posoperatoria/etiología , Cirugía Asistida por ComputadorRESUMEN
This is one of a series of statements discussing the utilization of GI endoscopy in common clinical situations. The Standards of Practice Committee of the American Society for Gastrointestinal Endoscopy prepared this text. In preparing this guideline, a MEDLINE literature search was performed, and additional references were obtained from the bibliographies of the identified articles and from recommendations of expert consultants. When little or no data exist from well-designed prospective trials, emphasis is given to results from large series and reports from recognized experts. Guidelines for appropriate utilization of endoscopy are based on a critical review of the available data and expert consensus. Further controlled clinical studies are needed to clarify aspects of this statement, and revision may be necessary as new data appear. Clinical consideration may justify a course of action at variance to these recommendations.