Dietary risk factors for colorectal cancer in Brazil: a case control study.

BACKGROUND: High meat intake and low consumption of vegetables, fruits and whole grains have been associated with increased risk of colorectal cancer in some relevant cohort studies conducted in distinct ethnic populations. The role of the dietary pattern on the risk of sporadic colorectal adenocarcinoma (SCA) in Brazil is unknown; therefore, it was the aim of the present study. METHODS: The dietary patterns of 169 patients with SCA and 101 controls were analysed by food frequency recall. Crude odds ratios were calculated and given within 95 % confidence intervals. RESULTS: Patients reported higher average intakes of beef (32.0 ± 1.8 versus 23.7 ± 1.6, P = 0.0069), chicken (18.1 ± 0.9 versus 12.2 ± 0.8, P = 0.0002), and pork (8.9 ± 0.9 versus 3.4 ± 0.5, P < 0.0001). These individuals had a 1.025, 1.069, and 1.121-fold increased risk of SCA. Similar consumption of fish, vegetables, fruits and whole grains was reported by patients and controls. CONCLUSIONS: Meat consumption is greater in patients with SCA in the Brazilian population. Considering the study population - characterized by ethnic heterogeneity -, the environmental factor related to food habits may be associated with higher incidence of this disease in Brazil.

Toll-like receptor 4, F4/80 and pro-inflammatory cytokines in intestinal and mesenteric fat tissue of Crohn's disease.

INTRODUCTION: Crohn's disease (CD) is a chronic intestinal ailment with a multifactorial etiology, whose incidence has increased during the last three decades. Recently, a role for mesenteric fat has been proposed in CD pathophysiology, since fat hypertrophy is detected nearby the affected intestinal area; however, there are few studies on this aspect. AIM: To evaluate inflammatory activity in intestinal mucosa and mesenteric fat tissue of patients with CD and controls. MATERIALS AND METHODS: Ten patients with ileocecal CD and 16 patients with non-inflammatory disease (control groups) were studied. The specimens were snap-frozen and the expression of TLR-4, F4/80, IL1-ß and IL-6 were determined by immunoblot of protein extracts. TLR4 RNA level were measured using RT-PCR. The t Test was applied (p<0.05). The local ethical committee approved the study. RESULTS: The intestinal mucosa of CD group had significantly higher protein levels of TLR-4, F4/80, IL-1ß and IL-6 than the controls. The gene expression of TLR4 was lower in the intestinal mucosa of CD compared to the control group. Regard the mesenteric fat tissue, there was no statistical difference related to TLR-4, F4/80, IL-1ß and IL-6 proteins expression. CONCLUSIONS: These findings may result from an up-regulation of macrophage activation and intracellular pathways activated by bacterial antigens, which are more important in intestinal mucosa than fat tissue in CD patients. This may represent an anomalous regulation of innate immunity and could contribute to the production of proinflammatory mediators and disease development.

Autophagy is decreased in mesenteric fat tissue but not in intestinal mucosae of patients with Crohn's disease.

Crohn's disease (CD) is a chronic intestinal disease with a multifactorial etiology. Recently, a role for mesenteric fat has been proposed in CD pathophysiology, since fat hypertrophy is detected close to the affected intestinal area; however, there are few studies regarding autophagy and the hypertrophied mesenteric tissue in CD. To evaluate autophagy-related proteins in intestinal mucosae and mesenteric fat of patients with CD and controls, patients with ileocecal CD (CD Group) and with non-inflammatory disease (FC Group) selected for surgery were studied. Expression of LC3-II was determined by immunoblotting of protein extracts. In addition, beclin-1, LC3 and Atg16-L1 RNA levels were measured using RT-PCR. The expression of LC3-II was significantly lower in the mesenteric tissue and higher in intestinal mucosae of CD when compared to controls. However, mRNA expression of autophagy-related proteins was similar when comparing the mesenteric fat groups. These findings suggest a defect in autophagy activation in the mesenteric fat tissue of CD individuals, which could be involved in the maintenance of the inflammatory process.

Differential expression of TLR2, TLR4 and JNK in mucosa of ileal pouches for ulcerative colitis. Is there a role for bacterial antigen pathway in asymptomatic patients?

INTRODUCTION: Ileal pouch-anal anastomosis (IPAA) is the preferred surgical procedure for patients with refractory ulcerative colitis (UC) and familial adenomatous polyposis (FAP). However, pouchitis is the most common complication after IPAA in UC patients and only occurs after ileostomy closure. Therefore, it is important to get more information about the role of the ileal pouch microbiota and mucosa susceptibility to inflammation in UC patients. Therefore, we evaluated Toll-like receptors (TLRs) expression in normal endoscopic and histological mucosa of the ileal pouch in patients with UC and FAP, in order to find any abnormality in this pathway in asymptomatic patients, which may contribute to pouchitis. MATERIALS AND METHODS: Twelve patients (six with UC and six with FAP) with "J" pouch reconstruction, after total rectocolectomy, were studied. Biopsies were obtained from the mucosa of the pouch. Normal ileum biopsies were obtained from six patients submitted to ileocolonoscopy with no abnormalities. The specimens were snap-frozen and the expressions of TLR2, TLR4 and JNK (nuclear signalization factor) were determined by immunoblot protein extract. RESULTS: Patients with UC had significantly higher protein levels of TLR4 than controls and FAP. The expressions of TLR2 and JNK were similar in the groups. CONCLUSION: Patients with UC had higher levels of TLR4, even in the absence of clinical, endoscopic and histological pouchitis. These findings may explain a tendency towards the up-regulation of intracellular pathways activated by bacterial antigens in UC patients, which could contribute to the production of proinflammatory mediators and pouchitis development.

Detection of epithelial apoptosis in pelvic ileal pouches for ulcerative colitis and familial adenomatous polyposis.

BACKGROUND: Ileal pouch-anal anastomosis (IPAA) is the surgical procedure of choice for patients with refractory ulcerative colitis (UC) and for familial adenomatous polyposis (FAP) with many rectal polyps. Pouchitis is one of the more frequent complications after IPAA in UC patients; however, it is rare in FAP. OBJECTIVE: Evaluate pro-apoptotic activity in endoscopically and histological normal mucosa of the ileal pouch in patients with UC and FAP. METHODS: Eighteen patients (nine with UC and nine with FAP) with J pouch after total rectocolectomy were studied. Biopsies were obtained from the mucosa of the pouch and from normal ileum. The specimens were snap-frozen and the expressions of Bax and Bcl-2 were determined by immunoblot of protein extracts and by immunohistochemistry analysis. FADD, Caspase-8, APAF-1 and Caspase-9 were evaluated by immunoprecipitation and immunoblot. RESULTS: Patients with UC had significantly higher protein levels of Bax and APAF-1, Caspase-9 than patients with FAP, but were similar to controls. The expressions of Bcl-2 and FADD, Caspase-8 were similar in the groups. Immunohistochemistry for Bax showed less intensity of immunoreactions in FAP than in UC and Controls. Bcl-2 immunostaining was similar among the groups. CONCLUSION: Patients with FAP present lower levels of pro-apoptotic proteins in all methods applied, even in the absence of clinical and endoscopic pouchitis and dysplasia in the histological analysis. These findings may explain a tendency of up-regulation of apoptosis in UC patients, resulting in higher rates of progression to pouchitis in these patients, which could correlate with mucosal atrophy that occurs in inflamed tissue. However, FAP patients had low pro-apoptotic activity in the mucosa, and it could explain the tendency to low cell turn over and presence of adenomas in this syndrome.

Evaluation of lateral lymph node metastases in advanced distal rectal cancer.

BACKGROUND/AIMS: The importance of lateral node dissection has not yet been fully investigated in advanced rectal cancer. To evaluate tumor cells in perirectal and lateral lymph nodes dissection from rectal adenocarcinomas considered free of disease by the hematoxylin-eosin test. METHODOLOGY: Fifteen patients submitted to neoadjuvant therapy and surgery for rectal adenocarcinoma with lateral node dissection were studied, retrospectively. The paraffin blocs of the nodes were analyzed with a immunohistochemical study and multiples cross section of the nodes. RESULTS: A total of 331 lymph nodes from these 15 patients were assessed, distributed as 258 perirectal nodes, 73 non perirectal, and 27 lateral nodes. The average was 22.1 lymph nodes per patient. Three patients out of 15 (20%) with histological negative lateral lymph node had occult metastasis detected by pancytokeratins AE1 and AE3. One of these cases didn't present tumor in the surgical specimen of the rectum. A case of positive lateral node identified by hematoxylin-eosin was also identified by immunohistochemical study. CONCLUSIONS: Although we had a small number of patients in the present study, lateral node dissection is important in selected cases of advanced cancer. Pancytokeratins AE1 and AE3 had a potential to improve study for detection of occult node metastasis, being helpful in rectal cancer prognosis.