COLONOSCOPY SURVEILLANCE IN ASYMPTOMATIC SUBJECTS WITH INCREASED RISK FOR COLORECTAL CANCER: CLINICAL EVALUATION AND COST ANALYSIS OF AN ITALIAN EXPERIENCE

The aim of this study was three-fold: (a) to present a surveillance plan for colorectal cancer prevention with colonoscopy, focused on first-degree relatives of colorectal cancer patients in the province of Ferrara (Italy); (b) to analyse the cost of colonoscopy at the University Hospital of Ferrara; and (c) to analyse the cost of the surveillance plan in our province. In January 2000, in the province of Ferrara, following a campaign of public sensitization, a plan of surveillance with colonoscopy was started, addressing the population at an increased risk for colorectal cancer (i.e. over 45-year-old first-degree relatives of patients with either colorectal cancer or adenomatous polyps revealed before 60 years of age). In addition, we estimated the cost of colonoscopy both at the University Hospital of Ferrara and of the surveillance plan. Between January 2000 and October 2003, 585 individuals at increased risk were interviewed. Five hundred and forty-four (94%) accepted to undergo a colonoscopy. By October 2003, 439 (81%) colonoscopies had been performed. Colonoscopy was normal in 330 individuals (75%). In 109 individuals (25%), 144 lesions were found: 35 patients (32%) had hyperplastic polyps, 66 (61%) had adenomas, and eight (7%) adenocarcinomas (six Dukes A, one Dukes B, and one Dukes C stage). Out of a total of 101 adenomas, 68 were tubular adenomas (67%), 24 tubulo-villous adenomas (24%), and nine adenomas with high-grade dysplasia (9%). The cost of colonoscopy at our hospital and the costs of the surveillance plan amounted to euro 130.84 (euro 169.57 with single biopsy) and euro 43,103.66 (euro 42 310.34/year), respectively. These data show (a) the efficacy of colonoscopy in the early diagnosis of colorectal cancer and premalignant lesions in first-degree relatives of colorectal cancer patients; (b) the low cost of colonoscopy at the centre performing the surveillance; and (c) the feasibility of screening and surveillance programmes for colorectal cancer prevention

Pathologic features of colorectal cancers detected by population screening in the province of Ferrara

Background and aim: Aim of the present study was to evaluate the histopathologic and clinical characteristics of colorectal carcinomas detected by means of the regional screening program in the province of Ferrara. Material and methods: The study included 92 infiltrating adenocarcinomas, 62 removed by surgery and 30 (32%) by endoscopic resection. Twenty-one patients with endoscopically removed malignant polyps subsequently underwent surgical resection with lymphadenectomy. Results: Most of the endoscopically removed malignant polyps (n=29) were localized in the distal colon (7 in the descending colon, 17 in the sigmoid colon and 5 in the rectum) and only one in the proximal colon. With regard to colorectal carcinomas removed by surgery, 16 were localized in the proximal colon (10 in the right and 6 in the transverse colon) and 46 in the distal colon (5 in the descending and 21 in the sigmoid colon and 20 in the rectum). Among the surgically removed tumors, 20 have been classified as TNM stage I, 18 as TNM stage II (all of them stage IIa), 18 as TNM stage III (6 stage IIIa, 7 IIIb and 5 IIIc) and 5 as TNM stage IV. Among the 21 carcinomas treated by endoscopic resection and subsequent surgical resection, two cases displayed metastases to lymph nodes (pN1). Analyzing all the adenocarcinomas identified by the screening program, 48 tumors (52.7%) were found to belong to the category with excellent prognosis, 26 (28.6%) to the category with good prognosis and only 17 (18.7%) to the category with poor prognosis. Most tumors were submitted to molecular analysis for microsatellite instability evaluation by means of a fluorescence-based PCR method and to immunohistochemical analysis to assess mismatch repair proteins expression (MLH1, MSH2, MSH6 and PMS2). These analyses allowed us to identify four MSI-H adenocarcinomas with loss of MMR protein expression (MLH1 in one case, MSH2 in one case and MSH6 in two cases), probably removed from patients with hereditary disease (Lynch syndrome). Conclusions: Our results indicate that the screening program allows to detect a large number of early stage colorectal carcinomas with excellent prognosis. This fact should contribute to obtain a mortality reduction for this neoplasm in the population

Third Round of Colorectal Cancer Screening in Ferrara (2009-2011): Prevalence of Colorectal Cancer and Advanced Adenoma and Comparison with a 2-year Prescreening Period (2003-2005)

Background and aims: In the Region of Emilia-Romagna (Italy), and particularly in Ferrara, colorectal cancer (CRC) is on the top of the national list of incidence and mortality. In March 2005, a population-based CRC screening campaign was started in Emilia-Romagna. The aim of this study was to report the screening activities of the third round (2009-2011) in Ferrara and to compare the CRC epidemiology over that period with the 2-year prescreening interval (2003-2005). Patients and methods: The screening program was based on a letter of invitation to perform an immunological FOBT (i-FOBT) sent to all the residents of Ferrara aged 50-69 years. If the i-FOBT was positive, the screenee was offered a colonoscopy while following a negative i-FOBT was invited by letter to repeat the test after two years. Adenomas were classified in: 1) low-risk adenomas (diameter <10 mm, villous component <25%, and low-grade dysplasia) and 2) high-risk adenomas (diameter 10 mm, at least 25% of villous component or high-grade dysplasia). If colonoscopy was negative, the screenee was invited to repeat the test after 5 years while if adenomatous polyps were found, endoscopic follow-up was started accordingly. In case of a CRC, necessary surgery was performed within 30 days from histological diagnosis. All patients undergoing an elective colorectal resection for CRC between April 2003 and March 2005 were reviewed and compared with the screnees of the third round (2009-2011) elected for a colorectal resection. The variables considered were: a) demographics (age, gender); b) type of surgical resection, c) pathology data, d) staging of the disease, and postoperative length of hospital stay (LOS). Results: From April 2009 to March 2011, 101,414 people in Ferrara were invited to i-FOBT. Of these, 50.039 (49,3%) adhered to the screening program and executed the test, 49.860 (49,2%) refused the invitation, and 1,515 (1,5%) were discarded for a variety of reasons. Of 50.039 people undergoing i-FOBT, 2.434 (4,9%; 46,0% men, 54,0% women) were i-FOBT positive and 47.571 (95%; 54,6% men, 45,3% women) were FOBT negative. Of 2.434 i-FOBT positive screenees, 274 had low-risk adenomas (11,2%; 64,2% men, 43,8% women), 352 had high-risk adenomas (14,5%; 64,7% men, 35,3% women), 17 had an early colorectal cancer [(pT1) 0.7%; 64,7% men, 35,3% women], and 59 an invasive colorectal cancer (2,4%; 49,2% men, 50,8% women). The comparison between the third round (2009-2011) and the prescreening period was as follows: Variables Prescreening period (2003-2005) N=275 Third screening round (2009-2011) N=46 p Age (years) 70,5 ± 11,9* 65,1 ± 8,6 <0.01 Gender (M : W) 52,7% : 47,3% 47,8% : 52,2% n.s.† Tumor stage - Stage 0 - Stage I - Stage II - Stage III - Stage IV 8,0% 11,3% 42,5% 32,0% 6,2% 26,1% 19,6% 26,1% 26,1% 2,1% <0.01 n.s. 0.05 n.s. n.s. LOS (days) 12 (6-30)‡ 10 (5-37) 0.01 *Mean ± standard deviation; †not significant; ‡Median (range) Conclusions: This study shows that in the third round of the screening program for CRC in Ferrara: 1) the adhesion to i-FOBT remained low (49,3%), and 2) there is a higher rate of early stage CRC as compared to the prescreening period. Thus, adequate campaigns of information for CRC screening are of utmost importance to increase the adhesion rate

Colorectal cancer screening in Ferrara: Results in early (2005-2009) and late (2009-2013) screening periods and surgical treatment of the screenees versus pre-screening (2003-2005) unselected population

Background and aims: The Region of Emilia-Romagna (Italy), and particularly Ferrara, has the top national incidence and mortality rates for colorectal cancer (CRC). In March 2005, a population-based CRC screening campaign was started in Emilia-Romagna. The aim of this study was two-fold: (1) to analyse the results of the screening program in Ferrara in both early (March 2005 - March 2009) and late (April 2009 - March 2013) screening periods and (2) to compare the cohort of screenes undergoing CRC surgical treatment in the early and late screening periods with an unselected pre-screening (April 2003 - March 2005) control population who underwent CRC surgical resection at the same institution. Patients and methods: All residents in Ferrara aged 50-69 years took part of the screening program receiving an invitation letter for immunological Faecal Occult Blood Test (i-FOBT). If i-FOBT positive, the screenees were offered a colonoscopy, while if i-FOBT negative were invited by letter to repeat the test after two years. Adenomas were classified in: (a) low-risk adenomas (diameter &lt;10 mm, villous component &lt;25%, and low-grade dysplasia) and (b) high-risk adenomas (diameter 10 mm, at least 25% of villous component or high-grade dysplasia). If colonoscopy was negative, the screenees were invited to repeat endoscopy after 5 years, while if adenomatous polyps were found endoscopic follow-up was started accordingly. In case of CRC diagnosis, necessary surgery was performed within 30 days. Demographic, surgical, and pathology data were reviewed for: (a) screenees undergoing surgical treatment for CRC in early and late screening periods and (b) all patients submitted to elective surgical resection for CRC at the S. Anna University Hospital in Ferrara during the pre-screening period April 2003 - March 2005. Statistical analysis. Data are presented as median (interquartile range 25-75) for normal distribution. Kruskal-Wallis, chi-square, and log rank tests were used to compare non-parametric data, proportions, and hospital length of stay (LOS), respectively. Results: From March 2005 to April 2009 (early screening period), 76,767 people in Ferrara were invited for i-FOBT. Of these, 36,930 (48%) adhered to the screening program and executed the test; 2,004 (5%) were i-FOBT positive, and 1,688 (84%) subsequently agreed to undergo colonoscopy. Endoscopy revealed 853 tumours (adenoma or cancer) confirmed on hystopathologic analysis. In the late screening period (April 2009 - March 2013), 86,763 subjects were invited for i-FOBT and 20,384 (46%) adhered; 1,827 (5%) were positive and 1,506 (82%) agreed to undergo colonoscopy. The endoscopy detected 731 histology proven adenomas or cancers. Data in early and late screening and pre-screening periods were as follows: Variables Pre-screening period (2003-2005) N=275 Early screening period (2005-2009) N=230 Late screening period (2009-2013) N=110 p Age (years) 72.3 (63.5-78.8) 64.0 (58.3-67.8) 64.1 (57.3-68.0) &lt;0.001 Gender (Men:Women) 145 (53%):130 (47%) 149 (65%):81 (35%) 58 (53%):52 (47%) 0.014 Tumor stage 0 I IIa IIb IIIa IIIb IIIc IV 22 (8%) 31 (11%) 99 (36%) 18 (7%) 4 (1%) 56 (20%) 28 (10%) 17 (6%) 54 (24%) 48 (21%) 49 (21%) 2 (1%) 7 (3%) 37 (16%) 30 (13%) 3 (1%) 24 (22%) 38 (34%) 17 (15%) 3 (3%) 0 21 (19%) 6 (6%) 1 (1%) &lt;0.001 . Tumor Site Right colon Transverse colon Left colon-rectum 103 (37%) 13 (5%) 159 (58%) 74 (32%) 7 (3%) 149 (65%) 35 (32%) 5 (4%) 70 (64%) 0.505 Hospital LOS (days) 12 (9-17) 10 (9-13) 9 (7-11) &lt;0.001 Conclusions: The adherence to i-FOBT remained low throughout the screening periods (48% early period vs. 46% late period); adequate campaigns of sensitization to CRC screening are therefore needed. The highest adherence rate in Italy was observed for colonscopy adherence among i-FOBT positive screeenes (≥82%). The screening program did not detect an increased proportion of proximal colorectal cancers, in contrast to other Authors. As expected, decreased patients’ age as well as earlier stage CRC diagnosis was achieved with the screening program. Reduction in postoperative hospital LOS was likely due to younger patients’ age and increased adoption of minimally invasive techniques

N-3 fatty acids in patients with multiple cardiovascular risk factors

BACKGROUND: Trials have shown a beneficial effect of n-3 polyunsaturated fatty acids in patients with a previous myocardial infarction or heart failure. We evaluated the potential benefit of such therapy in patients with multiple cardiovascular risk factors or atherosclerotic vascular disease who had not had a myocardial infarction. METHODS: In this double-blind, placebo-controlled clinical trial, we enrolled a cohort of patients who were followed by a network of 860 general practitioners in Italy. Eligible patients were men and women with multiple cardiovascular risk factors or atherosclerotic vascular disease but not myocardial infarction. Patients were randomly assigned to n-3 fatty acids (1 g daily) or placebo (olive oil). The initially specified primary end point was the cumulative rate of death, nonfatal myocardial infarction, and nonfatal stroke. At 1 year, after the event rate was found to be lower than anticipated, the primary end point was revised as time to death from cardiovascular causes or admission to the hospital for cardiovascular causes. RESULTS: Of the 12,513 patients enrolled, 6244 were randomly assigned to n-3 fatty acids and 6269 to placebo. With a median of 5 years of follow-up, the primary end point occurred in 1478 of 12,505 patients included in the analysis (11.8%), of whom 733 of 6239 (11.7%) had received n-3 fatty acids and 745 of 6266 (11.9%) had received placebo (adjusted hazard ratio with n-3 fatty acids, 0.97; 95% confidence interval, 0.88 to 1.08; P=0.58). The same null results were observed for all the secondary end points. CONCLUSIONS: In a large general-practice cohort of patients with multiple cardiovascular risk factors, daily treatment with n-3 fatty acids did not reduce cardiovascular mortality and morbidity. Copyright © 2013 Massachusetts Medical Society