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.

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.