RESUMO
BACKGROUND AND AIM: Gut flora/host interactions are fundamental for the maintenance of homeostasis. Evidence of possible regulatory effect of commensal bacteria on proliferative disorders of the colon is mounting. In this study, we explored the hypothesis that precancerous lesions, such as adenomas, present alteration of the local microflora and lead to an overproduction of antibacterial molecules of the innate immunity, namely α-defensins. Thus, the host-bacteria misbalance could represent a potential procarcinogenic factor. METHODS: Biopsies from adenomatous polyps and normal mucosa, in the rectum-sigmoid colon, were collected from 51 patients. Concentration of mucosal bacteria was evaluated by real-time polymerase chain reaction after extraction of total DNA. Total RNA was also extracted, and the defensin α-1, defensin-5, and defensin-6 gene expressions were evaluated by real-time polymerase chain reaction. Immunohistochemical study has been carried out to evaluate protein production and location. Antibacterial activity of adenomatous polyps mucosa was evaluated in vitro. RESULTS: Biopsies from adenomatous polyps had a significant relative reduction of mucosa adherent bacteria compared with normal tissue (20-fold relative reduction, P<0.05). Concomitantly, α-defensin expression and production were significantly increased in adenomas. Adenoma mucosa showed increased antibacterial activity in vitro compared with normal mucosa. CONCLUSIONS: Microflora dysbiosis occurs at the mucosal surface in colonic adenomas, and may represent a potential factor for dysplastic cell proliferation. Further studies are needed to confirm and define the role of this mechanism in colon carcinogenesis and the potential applications in the clinical setting.
Assuntos
Adenoma/microbiologia , Neoplasias do Colo/microbiologia , Pólipos do Colo/microbiologia , Mucosa Intestinal/microbiologia , Regulação para Cima , alfa-Defensinas/metabolismo , Adenoma/imunologia , Adenoma/patologia , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Biópsia , Colo/imunologia , Colo/microbiologia , Colo/patologia , Neoplasias do Colo/imunologia , Neoplasias do Colo/patologia , Pólipos do Colo/imunologia , Pólipos do Colo/patologia , DNA Bacteriano/análise , Humanos , Imunidade Inata , Mucosa Intestinal/imunologia , Mucosa Intestinal/patologia , Testes de Sensibilidade Microbiana , Reação em Cadeia da Polimerase , alfa-Defensinas/genética , alfa-Defensinas/imunologia , alfa-Defensinas/farmacologiaRESUMO
Cholangiocarcinoma (CCA) is the second most common primary liver cancer, characterized by a poor prognosis and resistance to chemotherapeutics. The progressive increase in CCA incidence and mortality registered worldwide in the last two decades and the need to clarify various aspects of clinical management have prompted the Italian Association for the Study of the Liver (AISF) to commission the drafting of dedicated guidelines in collaboration with a group of Italian scientific societies. These guidelines have been formulated in accordance with the Italian National Institute of Health indications and developed by following the GRADE method and related advancements.
Assuntos
Humanos , Colangiocarcinoma/classificação , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/prevenção & controle , Preparações Farmacêuticas , Mutação em Linhagem Germinativa/genéticaRESUMO
Elderly patients are at increased risk for peptic ulcer and cancer. Predictive factors of relevant endoscopic findings at upper endoscopy in the elderly are unknown. This was a post hoc analysis of a nationwide, endoscopic study. A total of 3,147 elderly patients were selected. Demographic, clinical, and endoscopic data were systematically collected. Relevant findings and new diagnoses of peptic ulcer and malignancy were computed. Both univariate and multivariate analyses were performed. A total of 1,559 (49.5%), 213 (6.8%), 93 (3%) relevant findings, peptic ulcers, and malignancies were detected. Peptic ulcers and malignancies were more frequent in >85-year-old patients (OR 3.1, 95% CI = 2.0-4.7, p = 0.001). The presence of dysphagia (OR = 5.15), weight loss (OR = 4.77), persistent vomiting (OR = 3.68), anaemia (OR = 1.83), and male gender (OR = 1.9) were significantly associated with a malignancy, whilst overt bleeding (OR = 6.66), NSAIDs use (OR = 2.23), and epigastric pain (OR = 1.90) were associated with the presence of peptic ulcer. Peptic ulcer or malignancies were detected in 10% of elderly patients, supporting the use of endoscopy in this age group. Very elderly patients appear to be at higher risk of such lesions.