FOXE1 and SYNE1 genes hypermethylation panel as promising biomarker in colitis-associated colorectal neoplasia.

BACKGROUND: Colitis-associated colorectal cancer affects individuals with inflammatory bowel disease (IBD) more often and earlier than cancer in the general population. Colonoscopy provides the surveillance gold standard. Changes to the surveillance intervals depending on endoscopic activity have been made, given data demonstrating that this is an important predictor of future dysplasia or cancer, but adjuvant, noninvasive clinical tools are still warranted to improve surveillance outcomes and to assist in management and interpretation of dysplasia. Methylation markers may be able to do this. METHODS: SYNE1, FOXE1, NDRG4, and PHACTR3 genes were screened using methylation-specific PCR that permit the methylation status of the genes to be determined directly on biopsies. Ninety-three patients with long-standing IBD undergoing a cancer surveillance program, and 30 healthy controls were studied. These included colorectal adenocarcinomas on a background of IBD of various stages (n = 25), IBD-associated dysplastic lesions (n = 29), adenomas arising on a background of ulcerative colitis (n = 8), samples from patients with no evidence of dysplasia or cancer but long-standing IBD (n = 31), and symptomatic patients found to have normal colonoscopy (controls) (n = 30). RESULTS: Gene promotor hypermethylation of SYNE1 and FOXE1 genes varied significantly between the groups and was increasingly likely with increased disease severity. Neither occurred in controls, whereas promotor hypermethylation was detected in biopsies of 60% of patients with colitis-associated colorectal cancer for FOXE1 and 80% for SYNE1. Promotor hypermethylation of either gene was highly significantly different between the groups overall. CONCLUSIONS: FOXE1 and SYNE1 hypermethylation markers demonstrated significantly increased expression in neoplastic tissue. Promoter methylation analysis of these genes might be a useful marker of neoplasia in long-standing IBD.

Sensitivity and specificity of magnetic resonance enterography in the clinical management of fistulizing Crohn's disease.

BACKGROUND: High diagnostic accuracy is reported for magnetic resonance enterography (MRE) in Crohn's disease (CD), but few studies have evaluated its role in abdominal fistulae. The primary aim of this study was to assess the reliability of MRE in the identification of internal fistulae in CD. METHODS: One hundred and eighty-six patients with moderate CD (CD Activity Index : 250-400) were prospectively selected from the inflammatory bowel disease clinic of Parma University Hospital. Eligible patients had already undergone nutritional screening, pancolonoscopy, and computed tomography enterography (CTE) in the month before enrollment. MRE was performed according to the study protocol. Additional fluoroscopic contrast-enhanced studies or surgical evaluation were used for discordance between CTE and MRE results. A consensus committee resolved equivocal findings. Surgical findings and/or fluoroscopic contrast-enhanced studies together with the clinical data were considered the composite "reference standard" to which the results of MRE were compared. RESULTS: MRE identified 22 internal fistulae in 21 patients (11%), of whom 4 (19%) also had perianal fistulae and found 7 abscesses (33%). Forty-one (22%) additional patients with perianal fistulae were identified. Thirteen patients (57%) with internal fistulae required enteral nutrition support. No statistically significant differences were found between MRE and CTE in fistula detection. There was also no significant difference between MRE and the composite diagnosis in those who underwent surgery (n = 8) and/or contrast-enhanced studies (n = 7). CONCLUSIONS: CTE and MRE accurately detect internal fistulae in CD. MRE is preferable because it avoids radiation. Reliable identification of internal fistulae by MRE should permit earlier and improved treatment.

Analysis of risk factors for complications in 262 cases of laparoscopic colectomy.

BACKGROUND: The aim of the study was to critically review the experience of our unit to identify all the risk factors that can predict the intra-operative and post-operative complications, early and late, that are related to the procedure. MATERIALS AND METHODS: We retrospectively reviewed 293 patients who had undergone laparoscopic colectomy at the General Surgery and Organ Transplantation Unit of the University Hospital of Parma between January 2001 and September 2009. Preoperative tumour staging was performed for all patients by pancolonoscopic examination, performed preferably by the operating surgeon, thoracic-abdominal-pelvic CT, and, for rectal neoplasia, with further input from endoscopic ultrasound and/or pelvic magnetic resonance (MR) imaging. The parameters evaluated for each patient included age, sex, body mass index (BMI), ASA score, preoperative blood tests, associated comorbidities, cancer, others surgical procedures, operative time, laparotomy conversion rate, intra- and post-operative complications, any returns to the operating theatre, length of hospital stay and mortality. RESULTS: A total of 293 laparoscopic colectomy procedures were performed in our unit between January 2001 and September 2009; we analysed 262 of the 293 cases treated, since the data were incomplete and not correctly stored for 31 cases. The overall rate of intra- and post-operative complications was 22.9% (60/262). In 40 cases (40/262, 15.26%), the complications were surgical, and in the other 20 cases (7.63%) they were medical; mortality rate of 0.38% (1/262). CONCLUSIONS: Rectal resection is significantly associated with a greater number of intra- and post-operative complications than the other surgical procedures examined. The laparoscopic approach maintains its benefits even in patients with known preoperative comorbidities and constitutes a feasible procedure even in patients who are obese and/or with ASA status > or = III.