RESUMEN
BACKGROUND & AIMS: Current stool DNA tests identify about half of individuals with colorectal cancers and miss most individuals with advanced adenomas. We developed a digital melt curve (DMC) assay to quantify low-abundance mutations in stool samples for detection of colorectal neoplasms and compared this test with other approaches. METHODS: We combined a melt curve assay with digital polymerase chain reaction and validated the quantitative range. We then evaluated its ability to detect neoplasms in 2 clinical studies. In study I, stool samples from patients with colorectal tumors with known mutations (KRAS, APC, BRAF, TP53) were assayed. In study II, archived stool samples from patients with advanced adenomas containing known KRAS mutations were assayed, along with controls. Results were compared with those from the stool DNA test PreGenPlus (Exact Sciences, Marlborough, MA), Hemoccult, and HemoccultSensa (both Beckman-Coulter, Fullerton, CA). RESULTS: The DMC assay detected samples in which only 0.1% of target genes were mutated. In study I, the DMC assay detected known mutations in 28 (90%) of 31 tumor samples and 6 (75%) of 8 advanced adenoma samples. In study II, the DMC assay detected 16 (59%) of 27 advanced adenoma samples that contained KRAS mutations, compared with 7% with the Hemoccult, 15% with the HemoccultSensa, and 26% with the PreGenPlus assays (P < .05 for each, compared with the DMC assay); specificities did not differ significantly. CONCLUSIONS: The DMC assay has a high level of sensitivity in detecting individuals with colon neoplasms and is better than current stool screening methods in detecting those with advanced adenomas. Further studies are indicated.
Asunto(s)
Adenoma/diagnóstico , Adenoma/genética , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/genética , ADN de Neoplasias/genética , Heces , Reacción en Cadena de la Polimerasa/métodos , Anciano , Estudios de Casos y Controles , Pruebas Diagnósticas de Rutina/métodos , Femenino , Humanos , Masculino , Tamizaje Masivo/métodos , Persona de Mediana Edad , Mutación , Sangre Oculta , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas p21(ras) , Sensibilidad y Especificidad , Proteína p53 Supresora de Tumor/genética , Proteínas ras/genéticaRESUMEN
PURPOSE: The primary end point of this study was to determine the risk factors that predict chronic pouchitis in those patients having ileal pouch-anal anastomosis. METHODS: A total of 237 patients with ulcerative colitis and undergoing ileal pouch-anal anastomosis by one surgeon at Oregon Health & Science University from 1993 to 2003 were evaluated. Data were gathered via retrospective chart reviews and by a questionnaire administered by telephone in 2004. Patients were excluded if there was less than one-year follow-up documented in the chart or they could not be contacted by telephone (n = 62), postoperative diagnosis of Crohn's disease (n = 3), failed ileoanal procedure (n = 1), and one-stage ileal pouch-anal anastomosis (n = 3), leaving 167 patients for evaluation. Patients were defined as having chronic pouchitis (> 3 episodes of pouchitis) or no pouchitis (< or = 3 episodes of pouchitis). Potential risk factors included number of operations used to perform ileal pouch-anal anastomosis, fulminant ulcerative colitis with two-stage operation, duration of diverting ileostomy after pouch formation, primary sclerosing cholangitis, other extraintestinal manifestations of ulcerative colitis, preoperative liver function tests, duration of ulcerative colitis, and the occurrence of postoperative complications. Initial univariate analysis was performed on all risk factors. Multivariate analysis was performed on all univariate risk factors with P values < 0.2. RESULTS: The prevalence of chronic pouchitis in our population was 46 percent. The following variables were identified during univariate analysis and entered into a multivariate model: preoperative serum albumin (P = 0.07), PSC (P = 0.126), duration of diverting ileostomy (P = 0.111), fulminant ulcerative colitis with two-stage operation, (P = 0.051), the presence of postoperative complications (P = 0.031), and the type of postoperative complications (anastomotic complications, P = 0.013). Patients who did not undergo diverting ileostomy at the time of their ileal pouch-anal anastomosis trended toward a lower likelihood of developing chronic pouchitis (P = 0.06). Multivariate analysis showed that patients with postoperative complications (53 percent, P = 0.042), specifically anastomotic complications, were more likely to develop chronic pouchitis (P = 0.005). Eight percent of patients had primary sclerosing cholangitis and 11 percent of patients had at least one extraintestinal manifestation of ulcerative colitis. Patients with primary sclerosing cholangitis were not more likely to develop chronic pouchitis (P = 0.168). Patients with extraintestinal manifestations also were not more likely to develop chronic pouchitis (P = 0.273). CONCLUSIONS: Chronic pouchitis is a frequent complication after ileal pouch-anal anastomosis. In this study patients with primary sclerosing cholangitis or other extraintestinal manifestations of ulcerative colitis were not more likely to develop chronic pouchitis. Patients with postoperative complications, specifically anastomotic complications after ileal pouch-anal anastomosis, were more likely to develop chronic pouchitis and may benefit from early strategies to prevent pouchitis.
Asunto(s)
Reservorios Cólicos , Complicaciones Posoperatorias/epidemiología , Reservoritis/epidemiología , Proctocolectomía Restauradora , Adulto , Enfermedad Crónica , Femenino , Humanos , Masculino , Análisis Multivariante , Valor Predictivo de las Pruebas , Prevalencia , Estudios Retrospectivos , Factores de Riesgo , Encuestas y CuestionariosRESUMEN
BACKGROUND: Recently updated practice guidelines give specific recommendations on surveillance and management of dysplasia in patients with ulcerative colitis. Previous studies of gastroenterologists in the United States and the United Kingdom demonstrated inconsistent surveillance techniques and limited understanding of the implications of dysplasia. OBJECTIVES: To demonstrate current surveillance practices and management of dysplasia among U.S. gastroenterologists. DESIGN: An 18-item questionnaire was mailed to 1000 gastroenterologists in the United States who were randomly selected from an American Gastroenterological Association mailing list. SETTING: United States. RESULTS: A total of 334 questionnaires were returned, and 312 were analyzed: 25% of respondents were in academic practice and 75% were in private practice. The majority were in practice more than 10 years. Nearly 80% begin surveillance colonoscopy at 8 to 10 years of disease duration for patients with pancolitis, and 54% report sending at least 31 biopsy specimens. Sixty percent of respondents did not recommend immediate colectomy for a confirmed finding of low-grade dysplasia, instead opting for repeat colonoscopy in 3 to 12 months. Physicians who took fewer biopsy specimens were more likely to recommend continued surveillance for low-grade dysplasia compared with those who took a greater number of biopsy specimens. LIMITATIONS: Limitations included the response rate of 33% and the potential for recall bias. CONCLUSIONS: Most U.S. gastroenterologists are practicing surveillance in patients with ulcerative colitis in accordance with published guidelines. There is widespread variation in the management of dysplasia and raised lesions, and the majority of U.S. gastroenterologists do not recommend immediate colectomy for a finding of low-grade dysplasia.
Asunto(s)
Competencia Clínica , Colitis Ulcerosa/patología , Colon/patología , Colonoscopía/estadística & datos numéricos , Gastroenterología/estadística & datos numéricos , Biopsia/métodos , Biopsia/estadística & datos numéricos , Colitis Ulcerosa/epidemiología , Progresión de la Enfermedad , Humanos , Oregon/epidemiología , Proyectos Piloto , Prevalencia , Estudios Retrospectivos , Washingtón/epidemiologíaRESUMEN
Inflammatory bowel disease (IBD) comprises a group of idiopathic diseases of the intestine characterized by chronic inflammation of the bowel with periods of exacerbation and remission. The 2 major categories of IBD are ulcerative colitis and Crohn's disease, and each disease is distinct both clinically and histologically. The exact cause of IBD remains unknown, but several theories have been proposed. Primary care physicians are frequently confronted with the initial diagnosis and management of patients with IBD, and medical treatment options have rapidly expanded in recent years. This article reviews the epidemiology and pathogenesis of IBD; its clinical presentations and complications, which are essential to understanding this complex disease; and the available treatment options.