RESUMEN
OBJECTIVE: Hepatologists and colonoscopists often hesitate to perform a colonoscopic polypectomy in patients with chronic liver disease (CLD), especially those with cirrhosis, because of the risk of postpolypectomy bleeding (PPB). We aimed to investigate the incidence and risk factors of delayed PPB after a colonoscopic polypectomy in patients with CLD. MATERIALS AND METHODS: In total, 152 patients with CLD who underwent colonoscopic polypectomy from December 2005 to December 2012 were retrospectively reviewed. RESULTS: Cirrhosis was identified in 80 (52.6%) patients. During the study period, 442 polyps were removed and delayed PPB developed in 14 (9.2%) patients. The incidence of delayed PPB was significantly higher in patients with cirrhosis than in those without the disease (13.8% [n = 11] vs. 4.2% [n = 3], p = 0.041). The polyp size (odds ratio, 1.087; 95% confidence interval, 1.009-1.172) and cirrhosis (odds ratio, 8.535; 95% confidence interval, 2.417-30.140) were independent risk factors for delayed PPB. In patients with cirrhosis, the optimal cut-off size to identify high-risk polyps for delayed PPB was 10 mm (area under the receiver operating characteristics curve, 0.737; sensitivity, 52%; specificity, 88%). CONCLUSION: Caution is needed when colonoscopic polypectomy is planned in patients with CLD who have larger polyps and cirrhosis.
Asunto(s)
Colectomía/efectos adversos , Pólipos del Colon/cirugía , Hepatopatías/complicaciones , Hemorragia Posoperatoria/epidemiología , Medición de Riesgo/métodos , Enfermedad Crónica , Pólipos del Colon/complicaciones , Colonoscopía , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Hepatopatías/epidemiología , Masculino , Persona de Mediana Edad , Hemorragia Posoperatoria/diagnóstico , Hemorragia Posoperatoria/etiología , República de Corea/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Factores de TiempoRESUMEN
BACKGROUND: Ongoing characterization of glioma has revealed that Akt signaling plays a crucial role in gliomagenesis. In mouse models, however, Akt alone was not sufficient to induce glioma. METHODS: We established transgenic zebrafish that overexpressed dominant-active (DA) human Akt1 or Rac1(G12V) (DARac1) at ptf1a domain and investigated transgenic phenotypes and mechanisms leading to gliomagenesis. RESULTS: Transgene expressions were spatiotemporally restricted without any developmental abnormality of embryos and persisted at cerebellum and medulla in adult zebrafish. DAAkt1 alone induced glioma (with visible bumps at the head), with incidences of 36.6% and 49% at 6 and 9 months, respectively. Histologically, gliomas showed various histologic grades, increased proliferation, and frequent invasion into the fourth ventricle. Preferential location of small tumors at periventricular area and coexpression of Her4 suggested that tumors originated from Ptf1a- and Her4-positive progenitor cells at ventricular zone. Gliomagenesis was principally mediated by activation of survival pathway through upregulation of survivin genes. Although DARac1 alone was incapable of gliomagenesis, when coexpressed with DAAkt1, gliomagenesis was accelerated, showing higher tumor incidences (62.0% and 73.3% at 6 and 9 months, respectively), advanced histologic grade, invasiveness, and shortened survival. DARac1 upregulated survivin2, cyclin D1, ß-catenin, and snail1a but downregulated E-cadherin, indicating that DARac1 promotes gliomagenesis by enhancing proliferation, survival, and epithelial-to-mesenchymal transition. On pharmacologic tests, only Akt1/2 inhibitor effectively suppressed gliomagenesis, inhibited cellular proliferation, and induced apoptosis in established gliomas. CONCLUSIONS: The zebrafish model reinforces the pivotal role of Akt signaling in gliomagenesis and suggests Rac1 as an important protein involved in progression.