Chiara Montana

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.

Altered Expression of Type-1 and Type-2 Cannabinoid Receptors in Celiac Disease

Anandamide (AEA) is the prominent member of the endocannabinoid family and its biological action is mediated through the binding to both type-1 (CB1) and type-2 (CB2) cannabinoid receptors (CBR). The presence of AEA and CBR in the gastrointestinal tract highlighted their pathophysiological role in several gut diseases, including celiac disease. Here, we aimed to investigate the expression of CBR at transcriptional and translational levels in the duodenal mucosa of untreated celiac patients, celiac patients on a gluten-free diet for at least 12 months and control subjects. Also biopsies from treated celiac patients cultured ex vivo with peptic-tryptic digest of gliadin were investigated. Our data show higher levels of both CB1 and CB2 receptors during active disease and normal CBR levels in treated celiac patients. In conclusion, we demonstrate an up-regulation of CB1 and CB2 mRNA and protein expression, that points to the therapeutic potential of targeting CBR in patients with celiac disease.

Omega-3 fatty acids in the maintenance of ulcerative colitis

Immunomodulation of the gut associated lynphoid tissue is a key issue in the clinical management of inflammatory bowel disease (IBD). Often toxic drugs are used to obtain clinical remission, sometimes in already immunocompromized patients. The presence of important co-morbidity might also heavily affect the clinical strategy. Polyunsaturated fatty acids (PUFAs) might represent a valid therapeutical option in IBD patients and further controlled clinical studies are warranted.

Abnormal anandamide metabolism in celiac disease

The endocannabinoid system has been extensively investigated in experimental colitis and inflammatory bowel disease, but not in celiac disease, where only a single study showed increased levels of the major endocannabinoid anandamide in the atrophic mucosa. On this basis, we aimed to investigate anandamide metabolism in celiac disease by analyzing transcript levels (through quantitative real-time reverse transcriptase-polymerase chain reaction), protein concentration (through immunoblotting) and activity (through radioassays) of enzymes responsible for anandamide synthesis (N-acylphosphatidyl-ethanolamine specific phospholipase D, NAPE-PLD) and degradation (fatty acid amide hydrolase, FAAH) in the duodenal mucosa of untreated celiac patients, celiac patients on a gluten-free diet for at least 12 months and control subjects. Also, treated celiac biopsies cultured ex vivo with peptic-tryptic digest of gliadin were investigated. Our in vivo experiments showed that mucosal NAPE-PLD expression and activity are higher in untreated celiac patients than treated celiac patients and controls, with no significant difference between the latter two groups. In keeping with the in vivo data, the ex vivo activity of NAPE-PLD was significantly enhanced by incubation of peptic-tryptic digest of gliadin with treated celiac biopsies. On the contrary, in vivo mucosal FAAH expression and activity did not change in the three groups of patients, and accordingly, mucosal FAAH activity was not influenced by treatment with peptic-tryptic digest of gliadin. In conclusion, our findings provide a possible pathophysiological explanation for the increased anandamide concentration previously shown in active celiac mucosa.

Minimally invasive thyroidectomy: a ten years experience

BACKGROUND The conventional thyroidectomy is the most frequent surgical procedure for thyroidal surgical disease. From several years were introduced minimally invasive approaches to thyroid surgery. These new procedures improved the incidence of postoperative pain, cosmetic results, patients quality of life, postoperative morbidity. The mini invasive video-assisted thyroidectomy (MIVAT) is a minimally invasive procedure that uses a minicervicotomy to treat thyroidal diseases. METHODS We present our experience on 497 consecutively treated patients with MIVAT technique. We analyzed the mean age, sex, mean operative time, rate of bleeding, hypocalcemia, transitory and definitive nerve palsy (6 months after the procedure), postoperative pain scale from 0 to 10 at 1 hour and 24 hours after surgery, mean hospital stay. RESULTS The indications to treat were related to preoperative diagnosis: 182 THYR 6, 184 THYR 3-4, 27 plummer, 24 basedow, 28 toxic goiter, 52 goiter. On 497 cases we have reported 1 case of bleeding (0,2%), 12 (2,4%) cases of transitory nerve palsy and 4 (0,8%) definitive nerve palsy. The rate of serologic hypocalcemia was 24.9% (124 cases) and clinical in 7.2% (36 cases); 1 case of hypoparathyroidism (0.2%). CONCLUSIONS The MIVAT is a safe approach to surgical thyroid disease, the cost are similar to CT as the adverse events. The minicervicotomy is really a minimally invasive tissue dissection.