Ulcerative colitis: pathogenesis.

The pathogenesis of ulcerative is still poorly understood. With the introduction of new culture-independent techniques the research on the intestinal microbiota has revealed an important reduction of Bacteroidetes and Firmicutes leading to a reduced biodiversity and dysbiosis in these patients. Going in depth, the intestinal barrier is covered under physiologic conditions by a mostly sterile mucus layer. Besides a reduction of mucus thickness or an alteration in mucus composition hypothesized for human ulcerative colitis, new evidence coming from mouse models has introduced a novel concept based on cellular stress due to misfolded mucus-associated proteins opening a new research area for the epithelial cell lining. A dysregulated immune response involving the innate (e.g. toll-like receptors, dendritic cells, etc) and the adaptive immune system (e.g. effector T-cells, regulatory T-cells, eosinophils, neutrophils, etc) may follow or precede the macroscopic lesions. The immune response in ulcerative colitis is represented principally by secretion of interleukin-5 and -13 being the latter responsible for the direct cytotoxicity against the epithelial cells. In latter stages the role of interleukin-17 producing cells, apparently differently regulated compared with Crohn's disease, remains to be elucidated. Finally, human ulcerative colitis is characterized by the presence of various types of autoantibodies including pANCA, antibodies against goblet cells and the isoforms 1 and 5 of human tropomyosin. The pathogenic potential of these antibodies is still debated. The present review focus on new achievements in the various scenarios converging to the clinical and histopathological feature of ulcerative colitis.

Ultraflex precision colonic stent placement for palliation of malignant colonic obstruction: a prospective multicenter study.

BACKGROUND: Many patients who develop obstructive colonic symptoms secondary to inoperable colorectal cancer will require palliative treatment. A minimally invasive and potentially long-lasting approach is placement of nitinol self-expanding metal stents (SEMS). OBJECTIVE: To determine the effectiveness and safety of a nitinol SEMS designed for colorectal use in the palliative treatment of malignant colonic obstruction. DESIGN: Prospective multicenter clinical study. SETTING: Nine European study centers. PATIENTS: Forty-four patients with malignant colonic obstruction. INTERVENTIONS: Placement of nitinol SEMS designed for colorectal use. MAIN OUTCOME MEASURES: Technical success, defined as accurate SEMS deployment with adequate stricture coverage, and clinical success, defined as decompression and relief of obstructive colonic symptoms maintained without intervention or serious device-related complications. RESULTS: Technical success was attained in 95% of patients, with 95% CI 85%-99%. After 6 months, the rate of clinical success was 81%, 95% CI 69%-96%. Survival at 6 months was 67%, 95% CI 54%-84%. Clinical success was maintained until death in 86% of the nonsurvivors. No perforations or SEMS-related deaths occurred. LIMITATION: This investigation was nonrandomized and did not include a control group. CONCLUSIONS: In a large prospective investigation, palliative placement of a nitinol SEMS designed for colorectal use was accomplished with a high rate of technical success. Durable clinical success was achieved in a high proportion of patients with low morbidity.

Insulated-tip knife endoscopic mucosal resection of large colorectal polyps unsuitable for standard polypectomy.

OBJECTIVES: Endoscopic mucosal resection (EMR) has been shown to be safe and effective. En bloc resection is often not achieved using conventional EMR. Insulated-tip knife (It-knife) EMR has been recently proposed for early gastric cancer dissection and removal. This study was conducted to evaluate the safety and efficacy in obtaining en bloc resection with It-knife EMR of large colonic lesions not resectable with standard endoscopic techniques. METHODS: A total of 29 patients (19 men, 10 women, mean age 67.5 yr, range 44-88) were included in the study. Lesions were considered not suitable for standard polypectomy because of large diameter (>3 cm), morphology, and/or position. Lesions were located in the rectum (N = 11), sigmoid: (N = 10), descending: (N = 4), transverse: (N = 2), and hepatic flexure (N = 2). After saline injection, circumferential incision and dissection of the lesions were attempted with the aim of achieving en bloc resection. RESULTS: En bloc resection was achieved in only 55.1% of the lesions (16 out of 29 patients). In the remaining cases, resection was completed with a piecemeal technique. The median size of the en bloc resected specimen was 3 x 3.4 cm. Complications occurred in four patients (13.7%). At histopathology, 13 patients had low-grade dysplasia, 15 high-grade dysplasia. One patient had a tumor invading the submucosa and was submitted to surgery. CONCLUSIONS: It-knife EMR is a promising technique for attempting en bloc resection of large colonic polyps. Adequate training and caution are required because it can be associated with a higher complication rate than with other EMR modalities.