Emilio Di Giulio

Treatment of Relapsing Mild-to-Moderate Ulcerative Colitis With the Probiotic VSL#3 as Adjunctive to a Standard Pharmaceutical Treatment: A Double-Blind, Randomized, Placebo-Controlled Study

OBJECTIVES:VSL#3 is a high-potency probiotic mixture that has been used successfully in the treatment of pouchitis. The primary end point of the study was to assess the effects of supplementation with VSL#3 in patients affected by relapsing ulcerative colitis (UC) who are already under treatment with 5-aminosalicylic acid (ASA) and/or immunosuppressants at stable doses.METHODS:A total of 144 consecutive patients were randomly treated for 8 weeks with VSL#3 at a dose of 3,600 billion CFU/day (71 patients) or with placebo (73 patients).RESULTS:In all, 65 patients in the VSL#3 group and 66 patients in the placebo group completed the study. The decrease in ulcerative colitis disease activity index (UCDAI) scores of 50% or more was higher in the VSL#3 group than in the placebo group (63.1 vs. 40.8; per protocol (PP) P=0.010, confidence interval (CI)95% 0.51–0.74; intention to treat (ITT) P=0.031, CI95% 0.47–0.69). Significant results with VSL#3 were recorded in an improvement of three points or more in the UCDAI score (60.5% vs. 41.4%; PP P=0.017, CI95% 0.51–0.74; ITT P=0.046, CI95% 0.47–0.69) and in rectal bleeding (PP P=0.014, CI95% 0.46–0.70; ITT P=0.036, CI95% 0.41–0.65), whereas stool frequency (PP P=0.202, CI95% 0.39–0.63; ITT P=0.229, CI95% 0.35–0.57), physicians rate of disease activity (PP P=0.088, CI95% 0.34–0.58; ITT P=0.168, CI95% 0.31–0.53), and endoscopic scores (PP P=0.086, CI95% 0.74–0.92; ITT P=0.366, CI95% 0.66–0.86) did not show statistical differences. Remission was higher in the VSL#3 group than in the placebo group (47.7% vs. 32.4%; PP P=0.069, CI95% 0.36–0.60; ITT P=0.132, CI95% 0.33–0.56). Eight patients on VSL#3 (11.2%) and nine patients on placebo (12.3%) reported mild side effects.CONCLUSIONS:VSL#3 supplementation is safe and able to reduce UCDAI scores in patients affected by relapsing mild-to-moderate UC who are under treatment with 5-ASA and/or immunosuppressants. Moreover, VSL#3 improves rectal bleeding and seems to reinduce remission in relapsing UC patients after 8 weeks of treatment, although these parameters do not reach statistical significance.

Detection of colorectal lesions with virtual computed tomographic colonography

BACKGROUND The aim of our study was to compare the performance of virtual computed tomographic colonography with that of conventional colonoscopy in a blinded, prospective study in 165 patients with suspected colorectal lesions. METHODS There were 165 patients, all referred for conventional colonoscopy, who underwent preliminary virtual computed tomographic colonography. Computed tomograhic images of all suspected lesions were analyzed and subsequently compared with conventional colonoscopy findings. RESULTS There were 30 colorectal cancers and 37 polyps identified at conventional colonoscopy. Virtual computed tomographic colonography correctly detected all cancers, as well as 11 of 12 polyps of 10 mm in diameter or larger (sensitivity, 92%); 14 of 17 polyps between 6 and 9 mm (sensitivity, 82%); and 4 of 8 polyps of 5 mm or smaller (sensitivity, 50%). The per-patient sensitivity and specificity were 92% and 97%, respectively. CONCLUSIONS Virtual computed tomographic colonography has a diagnostic sensitivity similar to that of conventional colonoscopy for the detection of colorectal lesions larger than 6 mm in diameter.

Atrophic body gastritis patients with enterochromaffin-like cell dysplasia are at increased risk for the development of type I gastric carcinoid.

Background/Aims In the presence of atrophic body gastritis, gastric carcinoid develops from gastric-body mucosa enterochromaffin-like cells. Few data exist on the prevalence of enterochromaffin-like dysplastic lesions in atrophic body gastritis patients and their presumed risk of evolution to carcinoid has never been assessed prospectively in humans. The aim of the present study was to investigate the prevalence and incidence of dysplastic and neoplastic enterochromaffin-like cell lesions in a consecutive series of patients with atrophic body gastritis. Methods A total of 130 atrophic body gastritis patients at diagnosis and 96 atrophic body gastritis patients at follow-up (median 30 months) underwent gastroscopy with multiple biopsies and fasting gastrinaemia evaluation. In patients with enterochromaffin-like cell dysplasia, a more detailed bioptic sampling at follow-up was performed. Results Of the 130 atrophic body gastritis patients, only one (0.7%) had a gastric carcinoid polyp, whereas enterochromaffin-like cell dysplasia was found in five patients (3.8%). At follow-up only one out of the 96 atrophic body gastritis patients (1%) was diagnosed as having a carcinoid polyp at 41 months. Enterochromaffin-like cell dysplasia was present in four additional patients (4.2%). Two atrophic body gastritis pernicious anaemia patients with enterochromaffin-like cell dysplasia developed a gastric carcinoid in the follow-up. Among nine atrophic body gastritis patients with enterochromaffin-like cell dysplasia, the incidence of carcinoid tumour was 22% compared to 1.1% of atrophic body gastritis patients without dysplasia (odds ratio: 26.00; 95% confidence interval: 2.089–323.52). During the follow-up, fasting gastrin levels increased significantly only in atrophic body gastritis patients with enterochromaffin-like cell dysplasia (mean 677.4 ± 66.1 vs 1112.2 ± 185.6;P = 0.0287). Conclusion This study provides the first clinical evidence that, in hypergastrinaemic atrophic body gastritis patients, enterochromaffin-like cell dysplasia carries a markedly increased risk for development of type I gastric carcinoid. This suggests that a more detailed endoscopic/bioptic procedure in this subgroup of atrophic body gastritis patients is able to detect gastric carcinoid at an early stage.

Reliability of endoscopy in the assessment of variceal features: The Italian Liver Cirrhosis Project

In order to evaluate the reliability of the endoscopic assessment of variceal features, 6 skilled endoscopists separately examined 28 patients with liver cirrhosis and varices. Definitions of variceal features were set up on the basis of the classification of the Japanese Research Society for Portal Hypertension. A new item, i.e. oesophageal lumen occupancy, and a semiquantitative rating system of endoscopic findings were introduced. Beyond chance agreement (Kappa index) was poor on the assessment of the extension of blue colour (0.33) and prevalence of cherry red spots or red weal marking (0.17) whereas was fair to good (0.40-0.66; P less than 10(-5)) on the following: location, size, lumen occupancy, presence of blue colour, presence and extension of red colour sign, haematocystic spot. We conclude that the endoscopic assessment of oesophageal varices based on these features is reliable; their prognostic value as predictors of bleeding risk should be prospectively assessed.

Type I gastric carcinoids: a prospective study on endoscopic management and recurrence rate.

Background: Type I gastric carcinoids (TIGCs) are neuroendocrine neoplasms arising from enterochromaffin-like cells in atrophic body gastritis. Data regarding their evolution in prospective series are scarce, thus treatment and follow-up are not codified. Our aim was to evaluate clinical outcome and recurrence in TIGCs managed by endoscopic approach. Methods: 33 patients (24 females; median age 65 years, range 23–81) were included and managed through endoscopic follow-up every 6–12 months, with lesion removal and multiple gastric biopsies. Baseline clinical and histological features were analyzed as risk factors by Cox regression. Results: At diagnosis, 7 tumors were intramucosal carcinoids and 26 were polyps (median diameter 5 mm, range 2–20), multiple in 17 patients. Associated severe atrophy was present in 21 cases (63.6%), while mild atrophy was found in 6 cases (18.2%). During a 46-month median follow-up, survival was 100% and no metastases occurred. One patient developed a less-differentiated carcinoid that was radically treated by surgery. 21 patients (63.6%) had recurrence after a median of 8 months, 14 of these (66.6%) had a second recurrence after a median of 8 months following the previous carcinoid removal. Median recurrence-free survival was 24 months. Neither clinical nor biochemical recurrence-predicting factors were found. Conclusions: Although about 60% of TIGCs had recurrence after endoscopic resection, endoscopic management may be considered safe and effective.

Research PaperReliability of endoscopy in the assessment of variceal features: The Italian Liver Cirrhosis Project*

In order to evaluate the reliability of the endoscopic assessment of variceal features, 6 skilled endoscopists separately examined 28 patients with liver cirrhosis and varices. Definitions of variceal features were set up on the basis of the classification of the Japanese Research Society for Portal Hypertension. A new item, i.e. oesophageal lumen occupancy, and a semiquantitative rating system of endoscopic findings were introduced. Beyond chance agreement (Kappa index) was poor on the assessment of the extension of blue colour (0.33) and prevalence of cherry red spots or red weal marking (0.17) whereas was fair to good (0.40-0.66; P less than 10(-5)) on the following: location, size, lumen occupancy, presence of blue colour, presence and extension of red colour sign, haematocystic spot. We conclude that the endoscopic assessment of oesophageal varices based on these features is reliable; their prognostic value as predictors of bleeding risk should be prospectively assessed.

Alteration of local microflora and α-defensins hyper-production in colonic adenoma mucosa

Background and Aim Gut flora/host interactions are fundamental for the maintenance of homeostasis. Evidence of possible regulatory effect of commensal bacteria on proliferative disorders of the colon is mounting. In this study, we explored the hypothesis that precancerous lesions, such as adenomas, present alteration of the local microflora and lead to an overproduction of antibacterial molecules of the innate immunity, namely &agr;-defensins. Thus, the host-bacteria misbalance could represent a potential procarcinogenic factor. Methods Biopsies from adenomatous polyps and normal mucosa, in the rectum-sigmoid colon, were collected from 51 patients. Concentration of mucosal bacteria was evaluated by real-time polymerase chain reaction after extraction of total DNA. Total RNA was also extracted, and the defensin &agr;-1, defensin-5, and defensin-6 gene expressions were evaluated by real-time polymerase chain reaction. Immunohistochemical study has been carried out to evaluate protein production and location. Antibacterial activity of adenomatous polyps mucosa was evaluated in vitro. Results Biopsies from adenomatous polyps had a significant relative reduction of mucosa adherent bacteria compared with normal tissue (20-fold relative reduction, P<0.05). Concomitantly, &agr;-defensin expression and production were significantly increased in adenomas. Adenoma mucosa showed increased antibacterial activity in vitro compared with normal mucosa. Conclusions Microflora dysbiosis occurs at the mucosal surface in colonic adenomas, and may represent a potential factor for dysplastic cell proliferation. Further studies are needed to confirm and define the role of this mechanism in colon carcinogenesis and the potential applications in the clinical setting.

Value-of-information analysis to guide future research in colorectal cancer screening

PURPOSE To identify the most useful areas for research in colorectal cancer (CRC) screening by using a value-of-information analysis. MATERIALS AND METHODS Cost-effectiveness of screening strategies, including colonoscopy, computed tomographic (CT) colonography, flexible sigmoidoscopy, and barium enema examination, were compared by using a Markov model. Monetary net benefit (NB), a measure of cost-effectiveness, was calculated by multiplying effect (life-years gained) by willingness to pay (100,000 dollars per life-year gained) and subtracting cost. A value-of-information analysis was used to estimate the expected benefit of future research that would eliminate the decision uncertainty. RESULTS In the reference-case analysis, colonoscopy was the optimal test with the highest NB (1945 dollars per subject invited for screening compared with 1862 dollars, 1717 dollars, and 1653 dollars for CT colonography, flexible sigmoidoscopy, and barium enema examination, respectively). Results of probabilistic sensitivity analysis indicated that colonoscopy was the optimal choice in only 45% of the simulated scenarios, whereas CT colonography, flexible sigmoidoscopy, and barium enema examination were the optimal strategies in 23%, 16%, and 15% of the scenarios, respectively. Only two parameters were responsible for most of this uncertainty about the optimal test for CRC screening: the increase in adherence with less invasive tests and CRC natural history. The expected societal monetary benefit of further research in these areas was estimated to be more than 15 billion dollars. CONCLUSION Results of value-of-information analysis show that future research on the optimal test for CRC screening has a large societal impact. Priority should be given to research on the increase in adherence with screening by using less invasive tests and to better understanding of the natural history of CRC.

Quality of colonoscopy in an organised colorectal cancer screening programme with immunochemical faecal occult blood test: the EQuIPE study (Evaluating Quality Indicators of the Performance of Endoscopy)

Objectives To assess variation in the main colonoscopy quality indicators in organised colorectal cancer (CRC) screening programmes based on faecal immunochemical test (FIT). Design Data from a case-series of colonoscopies of FIT-positive subjects were provided by 44 Italian CRC screening programmes. Data on screening history, endoscopic procedure and histology results, and additional information on the endoscopy centre and the endoscopists were collected. The adenoma detection rate (ADR) and caecal intubation rate (CIR) were assessed for the whole population and the individual endoscopists. To explore variation in the quality indicators, multilevel analyses were performed according to patient/centre/endoscopist characteristics. Results We analysed 75 569 (mean age: 61.3 years; men: 57%) colonoscopies for positive FIT performed by 479 endoscopists in 79 centres. ADR ranged from 13.5% to 75% among endoscopists (mean: 44.8%). ADR was associated with gastroenterology specialty (OR: 0.87 for others, 95% CI 0.76 to 0.96) and, at the endoscopy centre level, with the routine use of sedation (OR: 0.80 if occasional (<33%); 95% CI 0.64 to 1.00) and availability of screening-dedicated sessions (OR: 1.35; 95% CI 1.11 to 1.66). CIR ranged between 58.8% and 100% (mean: 93.1%). Independent predictors of CIR at the endoscopist level were the yearly number of screening colonoscopies performed (OR: 1.51 for endoscopists with >600 colonoscopies; 95% CI 1.11 to 2.04) and, at the endoscopy centre level, screening-dedicated sessions (OR: 2.18; 95% CI 1.24 to 3.83) and higher rates of sedation (OR: 0.47 if occasional; 95% CI 0.24 to 0.92). Conclusions The quality of colonoscopy was affected by patient-related, endoscopist-related and centre-related characteristics. Policies addressing organisational issues should improve the quality of colonoscopy in our programme and similar programmes.

Cost-effectiveness of endoscopic surveillance for gastric intestinal metaplasia

Background:  Patients with intestinal metaplasia (IM) are at increased risk for gastric cancer. Endoscopic surveillance has been shown to anticipate cancer diagnosis in an earlier stage. Cost‐effectiveness of endoscopic surveillance in IM patients is unknown. To assess the efficacy and cost‐effectiveness of an yearly endoscopic surveillance in patients with IM.