Azathioprine for prevention of clinical recurrence in Crohn's disease patients with severe endoscopic recurrence: an IG-IBD randomized double-blind trial.

OBJECTIVE: The recurrence of Crohn's Disease after ileo-colonic resection is a crucial issue. Severe endoscopic lesions increase the risk of developing early symptoms. Prevention and treatment of post-operative Endoscopic Recurrence (ER) have been studied with conflicting results. We compare effi cacy of azathioprine (AZA) vs. high-dose 5-aminosalicylic acid (5-ASA) in preventing clinical recurrence and treating severe post-operative ER. PATIENTS AND METHODS: We performed a 1-year multicenter randomized double-blind double-dummy trial. Primary end-points were endoscopic improvement and therapeutic failure (clinical recurrence or drug discontinuation due to lack of efficacy or adverse events) 12 months after randomization. We also performed a post-trial analysis on symptomatic and endoscopic outcomes 10 years after the beginning of the trial, with a median follow-up of 60 months. RESULTS: Therapeutic failure occurred in 8 patients (17.4%) within 12 months from randomization, with no significant difference between patients treated with 5-ASA (20.8%, 5 patients) and those with AZA (13.6%, 3 patients). Therapeutic failure was due to clinical recurrence in the 5-ASA group and to adverse events in the AZA group. Endoscopic improvement at 12 months was observed in 8 patients, 2 (11.8%) in the 5-ASA group and 6 (30%) in the AZA group. No serious adverse event was recorded. At the post-trial analysis (median follow-up 60 months), 47.8% (22/46) of patients experienced clinical recurrence: 54.2% (13/24) in the 5-ASA group and 40.9% (9/22) in the AZA group, p=0.546. Patients treated with AZA had lower risk of drug escalation. Clinical recurrence was associated with smoking (p=0.031) and previous surgery (p=0.003). CONCLUSIONS: Our trial indicates that there was no difference in terms of treatment failure between 5-ASA and AZA in patients with severe ER. The main limit of AZA is its less favorable safety profile.

Colorectal cancer in patients with type 2 diabetes mellitus: a single-center experience.

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of colorectal cancer (CRC). The aim of the study is to evaluate the prevalence of CRC in a cohort of Caucasian patients with T2DM and the association with other variables previously known to be related with increased risk of CRC. We retrospectively evaluated the data of 741 consecutive Caucasian patients with T2DM who underwent colonoscopic screening in our tertiary referral center. A control cohort of 333 patients with thyroid disease was selected to evaluate the difference in the incidence of CRC. At a median follow-up of 132.5 months (range 33.3-175.7), 67 cases of cancer (prevalence 9%) occurred; among these, 14 cases of CRC were reported (prevalence 1.88%) among the diabetic patients, while only two case (one of these was a CRC) (overall prevalence 0.006%, prevalence of CRC 0.003%) occurred in the control group; the difference between the prevalence of CRC was statistically significant (chi-square 4.21, p=0.04). The median duration of T2DM to CRC diagnosis was 168 months (range 12-768). At the univariate analysis, older age (p=0.001, r 0.138) and diabetes duration (p=0.001, r 0.138) were related to higher risk of cancer, while metformin seems to be protective towards cancer (p=0.07, r -0.098). In the subset of patients with CRC, the age (RR = 2.25; 95% CI: 0.30 - 17.31; p less than 0.001), the diabetes duration (RR = 1.93; 95% CI: 0.25 – 14.77; p = 0.001) and the sulphonylureas treatment (RR = 2.33; 95% CI: 0.78 – 7.38; p = 0.007) were independently correlated with CRC. In our study, the prevalence of CRC in the cohort of patients with T2DM was higher compared to that from the National Tumor Register in 2010 (0.5%). Furthermore, we could speculate that sulphonylureas may play a role in CRC carcinogenesis impairing the physiological insulin secretion.

Y-shaped bilateral self-expandable metallic stent placement for malignant hilar biliary obstruction: data from a referral center for palliative care.

BACKGROUND AND AIM: Malignant hilar strictures are a clinical challenge because of the current therapeutic approach and the poor prognosis. In recent years, self-expandable metallic stents have proven more effective than plastic stents for palliation of malignant hilar strictures, with the bilateral stent-in-stent technique registering a high success rate. We report our experience with Y-shaped endoscopic self-expandable metallic stents placement for treatment of advanced malignant hilar strictures. METHODS: From April 2009 to August 2012, we prospectively collected data on patients treated with Y-shaped SEMS placement for advanced malignant hilar carcinoma. Data on technical success, clinical success, and complications were collected. RESULTS: Twenty patients (9 males) were treated (mean age 64.2 ± 15.3 years). The grade of malignant hilar strictures according to the Bismuth classification was II in 5 patients (25%), IIIa in 1 (5%), and IV in 14 (70%). The mean bilirubin level was 14.7 ± 4.9 mg/dL. Technical success was achieved in all patients, with a significant reduction in bilirubin levels (2.9 ± 1.7 mg/dL). One patient experienced cholangitis as early complication, while in 2 patients stent ingrowth was observed. No stents migration was recorded. There was no procedure-related mortality. At the end of the follow-up (7.1 ± 3.1 months), 13 of the 20 patients (65%) had died. CONCLUSIONS: Our experience confirms endoscopic bilateral self-expandable metallic stents placement with stent-in-stent technique (Y-shaped configuration) as a feasible, effective, and safe procedure for palliation of unresectable malignant hilar strictures.

Fully covered self-expandable metallic stents in benign biliary strictures: a multicenter study on efficacy and safety.

BACKGROUND AND STUDY AIM: Benign biliary diseases include benign biliary stricture (BBS), lithiasis, and leaks. BBSs are usually treated with plastic stent placement; use of uncovered or partially covered metallic stents has been associated with failure related to mucosal hyperplasia. Some recently published series suggest the efficacy of fully covered self-expandable metal stents (FCSEMSs) in BBS treatment. We aimed to assess the efficacy and safety of FCSEMS in a large series of patients with BBS and a long follow-up.  PATIENTS AND METHODS: Prospective multicenter clinical study at three tertiary referral centers: ISMETT/UPMC Italy, Palermo, San Paolo Hospital, Milan, and the ARNAS Civico Hospital, Palermo, Italy. All consecutive patients with BBS were treated with placement of FCSEMS rather than plastic stents, as first approach (11 patients, 17.7 %), or as a second approach after failure of other treatments (51 patients, 82.2 %). RESULTS: From January 2008 to March 2011, 62 patients (40 male) were included. Mean period of FCSEMS indwelling was 96.7 days (standard deviation [SD] 6.5 days). In 15 patients (24.2 %) the SEMS migrated. Resolution of BBS occurred in 56 patients (90.3 %), while in 6 (9.6 %) the treatment failed. Mean (SD) follow-up after SEMS removal was 15.9 (10) months. FCSEMS placement as first- or second-line approach showed no difference in failure. Recurrence was observed in 4 /56 patients (7.1 %); all were transplant recipients: P = 0.01; odds ratio (OR) 1.2, confidence interval (CI) 1.1 - 1.3. CONCLUSIONS: Despite the noteworthy migration rate, FCSEMSs should be considered effective for refractory benign biliary strictures. Further studies are needed to assess their role as a first approach in the management of BBS.

Endovenous thermal ablation. Standardization of laser energy: literature review and personal experience.

Endovenous laser treatment is a new, minimally invasive technique for ablation of the incompetent great and small saphenous vein and their tributaries. Although the satisfactory safety/efficacy results of this technique, literature is poor regarding standardization of the energy needed to ablate the incompetent vein in order to have success and durability of the procedure. The aim of this paper is a review of the literature to find out if authors with large experience on endovenous laser treatment achieved a standardization of the delivered energy at the incompetent vein wall and if new concepts proposed by the authors, like cold saline anesthesia, echogenic vein occlusion and regular distribution of laser energy to the vein wall, can improve the technique in order to have optimum results.

[Thrombin]. / La trombina.

A survey of the present knowledge on the relationship between structure and biological activity of thrombin is made. The recent pharmacological research on the block of thrombin function is then evaluated.

Epidemiology of inflammatory bowel disease in Italy.

The incidence of inflammatory bowel diseases is similar throughout Italy. Two prospective multicentre studies in the same period have shown an incidence very similar to Northern Europe. The incidence of ulcerative colitis ranged from 3.4 to 10.5. The incidence of Crohn's disease ranged from 1.9 to 6.6. The time trends seem to indicate an increase in both diseases. The need to set up General Registries of disease is underlined. The clinical behaviour and the diagnostic approach are homogeneous throughout the country. Compared to Northern Europe, surgery was less common in ulcerative colitis. Among the risk factors, familial occurrence has been shown to have the same prevalence as in Northern Europe suggesting a common genetic background. Studies on other risk factors are warranted considering the lack of data. Data on mortality show that there is a decrease in deaths in ulcerative colitis and a slight increase in mortality for Crohn's disease in the first few years after diagnosis. A retrospective study on costs has shown a greater economic burden from ulcerative colitis, however, new multicentre prospective studies are necessary.

Mortality and causes of death in celiac disease in a Mediterranean area.

No data on mortality in celiac disease are currently available in southern Europe. Our aim was to evaluate mortality and the cause of death in adult celiac disease in a Mediterranean area. In all, 228 adults with celiac disease were histologically diagnosed in our department from 1980 to 1997. Full information on their state of health was obtained in 216 of 228 patients. A tabulation of patient-years at risk was constructed in terms of age at diagnosis and the interval from diagnosis. Standardized mortality ratio was calculated by dividing the number of observed deaths by the number of expected deaths. Twelve deaths were observed, whereas 3.12 deaths were expected (SMR = 3.8; 95% CI 2-7). The increased mortality was mainly observed within four years from diagnosis (8 observed; 1.4 expected) (SMR = 5.8; 95% CI 2.5-11.5). Twelve tumors were observed (six lymphomas). In conclusion, mortality from adult celiac disease in our geographical area is increased compared with the general population, and this increased risk seems due to non-Hodgkin's lymphoma.

Relationship between site of disease and familial occurrence in Crohn's disease.

Concordance in the extent of disease among the family members of patients with Crohn's disease has not been widely investigated. Furthermore, the relationship between the site of the disease and familial occurrence has never been studied. Our aim was to evaluate the familial occurrence of Crohn's disease in the various sites. Nine hundred thirty-four patients with Crohn's disease, observed consecutively in two gastrointestinal departments, were investigated to determine first-degree familial incidence (in both Crohn's disease and ulcerative colitis). Whenever two or more members were attending the same clinic, only one was regarded as a propositus. The analysis, therefore, was carried out on 882 patients. The exact site of the disease was determined in all patients either at diagnosis or during the follow-up by colonoscopy and by small bowel enema. The rate of concordance in the extent of disease and familial occurrence in the various sites was evaluated and the difference was calculated by chi-square test. Sixty-one propositi were identified among all the patients. Forty-nine had familial occurrence for the same disease (concordant patients), whereas 12 had at least one relative with ulcerative colitis (discordant patients). In 44 propositi with only one relative affected, the rates of concordance in the extent of the disease were 84, 68, 18, and 0% respectively, for the ileum, the ileum-right colon, the ileum-total colon, and the colon. The number of propositi in the various sites was as follows: 4 of 162 (2.4%) patients with the disease located in the colon, 1 of 9 (11%) with the jejunum site, 24 of 380 (6.3%) with the ileum site, 16 of 165 (9.7%) with the ileum and right colon site, and 16 of 164 (9.7%) with the ileum and total colon site. The chi-square values of propositi distribution among other sites and the colon was, respectively, as follows: jejunum, 2.2 (N.S.); ileum, 3.4 (P = 0.06); ileum and right colon, 7.4 (P = 0.006); and ileum and total colon, 7.4 (P = 0.006). This study shows a pronounced concordance in the site of the disease for family members with Crohn's disease and suggests that familial occurrence in Crohn's disease is less frequent when the disease is located in the colon rather than elsewhere.