Leonardo Ventura

Influence of seasonal variations in ambient temperatures on performance of immunochemical faecal occult blood test for colorectal cancer screening: observational study from the Florence district

Background Faecal occult blood testing (FOBT) in population screening has proved to be effective in reducing mortality from colorectal cancer. In Italy a latex agglutination FOBT has been adopted for a single-sample screening programme. The aim of this study was to examine the performance of FOBTs in the Florence screening programme over several seasons to evaluate the impact of variations in ambient temperature on the performance of the screening test. Methods Measured haemoglobin (Hb) concentrations were aggregated into seasons with their average ambient temperature (AAT). Using logistic regression, the AAT over the period preceding the test measurement was analysed. This period included the time between faecal sampling and return of the test sample (mean 7 days) and the time in the laboratory refrigerator before analysis (mean 4 days). The AAT from days 5–11 before analysis of the test sample was considered a determinant of test positivity. The Kruskal–Wallis rank test was used to evaluate the significance of seasonal and/or AAT-related differences in Hb concentration. A logistic regression model adjusted for sex, age, season and screening episode (first or repeated examination) was constructed. Results 199 654 FOBT results were examined. Mean FOBT seasonal Hb concentrations (ng/ml) were: spring 27.6 (95% CI 26.2 to 29.1); summer 25.2 (95% CI 23.1 to 27.3); autumn 29.2 (95% CI 27.7 to 30.6); winter 29.5 (95% CI 27.9 to 31.1). Logistic regression showed that there was a 17% lower probability of the FOBT being positive in summer than in winter. The results of the logistic regression showed that an increase in temperature of 1°C produced a 0.7% reduction in probability of a FOBT being positive. In the summer the probability of detecting a cancer or an advanced adenoma was about 13% lower than in the winter. Conclusions This study showed that there is a significant fall in Hb concentration at higher ambient temperatures. These results will have important implications for the organisation of immunochemical FOBT-based screening programmes, particularly in countries with high ambient temperatures.

Human papillomavirus infection and risk factors in a cohort of Tuscan women aged 18-24: results at recruitment

BackgroundThere is conclusive evidence that human papillomavirus (HPV) infections of the cervix are a necessary cause of cervical cancer. In Italy there are consistent data of HPV prevalence in women aged 25 - 64 years, but there is limited data for younger women. The objective of this on-going 3-year prospective cohort study is to investigate the prevalence, acquisition, clearance and persistence of HPV infections in young Tuscan women and the risk factors correlated with such events.MethodsOne thousand and sixty-six women aged between 18 and 24 years were enrolled and received an initial HPV test. They were asked to return to the clinic over the study period for further tests every 12 months, if their HPV HR result was negative, or every 6 months, if positive. Additionally, women with an HPV positive result were given a cytological examination and if the cytological diagnosis was ASC-US or more severe, only women with HPV HR, were referred for colposcopy.ResultsWe present here data for the enrolment phase of the study. At baseline, within the study sample, just under 30% of women were infected by HPV and 19.3% of women were infected with oncogenic types. A relationship was highlighted between HPV infection, number of sexual partners (in particularly in the last 3 years) and the lifetime number of partners partners. Condom use showed a slight protective effect in univariate analysis but these data were not statistically significant in multivariate analysis. The association between HPV infection and demographic and behavioural variables were tested by crude odds ratio (OR). Multivariate logistic regression was applied to compute the adjusted odds ratios.ConclusionsThe prevalence of oncogenic HPV types was high in young Tuscan women. The 3-year follow-up of this cohort may provide a better understanding of the processes of acquisition, clearance and persistence of infection and the correlated risk factors.

Reduced and Full-Preparation CT Colonography, Fecal Immunochemical Test, and Colonoscopy for Population Screening of Colorectal Cancer: A Randomized Trial

BACKGROUND Population screening for colorectal cancer (CRC) is widely adopted, but the preferred strategy is still under debate. We aimed to compare reduced (r-CTC) and full cathartic preparation CT colonography (f-CTC), fecal immunochemical test (FIT), and optical colonoscopy (OC) as primary screening tests for CRC. METHODS Citizens of a district of Florence, Italy, age 54 to 65 years, were allocated (8:2.5:2.5:1) with simple randomization to be invited by mail to one of four screening interventions: 1) biennial FIT for three rounds, 2) r-CTC, 3) f-CTC, 4) OC. Patients tested positive to FIT or CTC (at least one polyp ≥6mm) were referred to OC work-up. The primary outcomes were participation rate and detection rate (DR) for cancer or advanced adenoma (advanced neoplasia). All statistical tests were two-sided. RESULTS Sixteen thousand eighty-seven randomly assigned subjects were invited to the assigned screening test. Participation rates were 50.4% (4677/9288) for first-round FIT, 28.1% (674/2395) for r-CTC, 25.2% (612/2430) for f-CTC, and 14.8% (153/1036) for OC. All differences between groups were statistically significant (P = .047 for r-CTC vs f-CTC; P < .001 for all others). DRs for advanced neoplasia were 1.7% (79/4677) for first-round FIT, 5.5% (37/674) for r-CTC, 4.9% (30/612) for f-CTC, and 7.2% (11/153) for OC. Differences in DR between CTC groups and FIT were statistically significant (P < .001), but not between r-CTC and f-CTC (P = .65). CONCLUSIONS Reduced preparation increases participation in CTC. Lower attendance and higher DR of CTC as compared with FIT are key factors for the optimization of its role in population screening of CRC.

Screening for colorectal cancer with FOBT, virtual colonoscopy and optical colonoscopy: study protocol for a randomized controlled trial in the Florence district (SAVE study)

BackgroundColorectal cancer (CRC) is the most frequent cancer in Europe. Randomized clinical trials demonstrated that screening with fecal occult blood test (FOBT) reduces mortality from CRC. Accordingly, the European Community currently recommends population-based screening with FOBT. Other screening tests, such as computed tomography colonography (CTC) and optical colonoscopy (OC), are highly accurate for examining the entire colon for adenomas and CRC. Acceptability represents a critical determinant of the impact of a screening program. We designed a randomized controlled trial to compare participation rate and diagnostic yield of FOBT, CTC with computer-aided diagnosis, and OC as primary tests for population-based screening.Methods/DesignA total of 14,000 subjects aged 55 to 64 years, living in the Florence district and never screened for CRC, will be randomized in three arms: group 1 (5,000 persons) invited to undergo CTC (divided into: subgroup 1A with reduced cathartic preparation and subgroup 1B with standard bowel preparation); group 2 (8,000 persons) invited to undergo a biannual FOBT for three rounds; and group 3 (1,000 persons) invited to undergo OC. Subjects of each group will be invited by mail to undergo the selected test. All subjects with a positive FOBT or CTC test (that is, mass or at least one polyp ≥6 mm) will be invited to undergo a second-level OC. Primary objectives of the study are to compare the participation rate to FOBT, CTC and OC; to compare the detection rate for cancer or advanced adenomas of CTC versus three rounds of biannual FOBT; to evaluate referral rate for OC induced by primary CTC versus three rounds of FOBT; and to estimate costs of the three screening strategies. A secondary objective of the study is to create a biological bank of blood and stool specimens from subjects undergoing CTC and OC.DiscussionThis study will provide information about participation/acceptability, diagnostic yield and costs of screening with CTC in comparison with the recommended test (FOBT) and OC.Trial registrationClinicalTrials.gov Identifier: NCT01651624.

Computed tomographic colonography in subjects with positive faecal occult blood test refusing optical colonoscopy.

BACKGROUND Refusal of colonoscopy is a drawback of colorectal cancer screening programmes based on faecal occult blood test. Computed-tomographic-colonography is generally more accepted than colonoscopy. AIM To compare adherence to computed-tomographic-colonography and second-invitation colonoscopy in subjects with positive faecal test refusing colonoscopy. METHODS We performed a prospective study in 198 subjects with positive faecal test who refused first referral to colonoscopy in one endoscopy service of the Florence screening programme. Subjects were randomly invited to computed-tomographic-colonography (n = 100) or re-invited to colonoscopy (n = 98). Mail invitation was followed by a questionnaire administered by phone. Computed-tomographic-colonography findings were verified with colonoscopy. RESULTS 32 subjects could not be reached, 71 (35.9%) had undergone colonoscopy on their own; 4 were excluded for contraindications; 30/48 (62.5%) in the computed-tomographic-colonography arm and 11/43 (25.6%) in the colonoscopy arm accepted the proposed examinations (p < 0.001). Four advanced adenomas and 1 cancer were found in the 28 subjects who ultimately underwent computed-tomographic-colonography and 2 advanced adenomas and 2 cancers in the 9 subjects who ultimately underwent second-invitation colonoscopy. CONCLUSION Subjects with positive faecal occult blood test refusing colonoscopy show a higher adherence to computed-tomographic-colonography than to second invitation colonoscopy.

Breast cancer mortality trends in Italy by region and screening programme, 1980–2008

Objectives To describe trends in breast cancer mortality in 14 Italian regions representing 90% of the Italian population, and in the country overall, in relation to the diffusion of organized or opportunistic breast cancer screening programmes. Settings: Breast cancer mortality figures from 1980–2008 in Italy and 14 Italian regions were retrieved from the National Statistics Institute. Methods Estimated annual percent change (EAPC) was calculated for three time-periods (1980–1989, 1990–1999, 2000–2008). To estimate the age-adjusted and age-specific EAPC, trends in mortality based on annual data were examined using a log-linear regression model, and the year of death as a regressor variable. Results In the period 1980–1989 an increasing trend was observed in Italy overall (EAPC = +1.1%; 95% confidence interval [95%CI]: + 0.9%; + 1.3%) and in the 14 regions. In the second decade a decreasing trend was recorded both overall in Italy (EAPC = −1.6%; 95CI:−1.8%;−1.4%) and in all the regions. Between 2000–2008 a slightly decreasing trend was observed in Italy overall (EAPC = −0.8%; 95%CI:−1.0%;−0.5%). A steeper and earlier decrease compared with the rest of Italy was observed in 1990–1999 in Liguria (EAPC = −3.1%; 95%CI:−4.0%,−2.1%), Lombardy (EAPC = −2.3%; 95%CI:−2.8%;−1.9%), and Tuscany (EAPC = −3.0%; 95%CI:−3.7%;−2.2%), mainly due to the 55–64 age−group. There were significant EAPCs between −4.1% and −3.7% in these three regions, 2.5–3.0 times greater than in the rest of Italy (EAPC = −1.4%). Conclusions This earlier decline in three Italian regions could be partially attributable to local organized screening programmes implemented earlier than in the rest of Italy, and to opportunistic screening that became more common in 1990s.

Impact of a new sampling buffer on faecal haemoglobin stability in a colorectal cancer screening programme by the faecal immunochemical test.

Haemoglobin (Hb) stability in faecal samples is an important issue in colorectal cancer screening by the faecal immunochemical test (FIT) for Hb. This study evaluated the performance of the FIT-Hb (OC-Sensor Eiken) used in the Florence screening programme by comparing two different formulations of the buffer, both in an analytical and in a clinical setting. In the laboratory simulation, six faecal pools (three in each buffer type) were stored at different temperatures and analysed eight times in 10 replicates over 21 days. In the clinical setting, 7695 screenees returned two samples, using both the old and the new specimen collection device (SCD). In the laboratory simulation, 5 days from sample preparation with the buffer of the old SCD, the Hb concentration decreased by 40% at room temperature (25°C, range 22–28°C) and up to 60% at outside temperature (29°C, range 16–39°C), whereas with the new one, Hb concentration decreased by 10%. In the clinical setting, a higher mean Hb concentration with the new SCD compared with the old one was found (6.3 vs. 5.0 µg Hb/g faeces, respectively, P<0.001); no statistically significant difference was found in the probability of having a positive result in the two SCDs. Better Hb stability was observed with the new buffer under laboratory conditions, but no difference was found in the clinical performance. In our study, only marginal advantages arise from the new buffer. Improvements in sample stability represent a significant target in the screening setting.

Faecal immunochemical test in subjects not attending screening computed tomography colonography and colonoscopy in a randomized trial

The aim of this study was to evaluate the participation and yield of the faecal immunochemical test (FIT) in nonattendees for computed tomography colonography (CTC) or optical colonoscopy (OC) screening, in the setting of a randomized trial. In the SAVE trial, 16087 individuals were randomly assigned and invited to one of four interventions for colorectal cancer screening: (i) biennial FIT for three rounds; (ii) reduced-preparation CTC; (iii) full-preparation CTC; and (iv) OC. Nonattendees of reduced-preparation CTC, full-preparation CTC and OC groups were invited to FIT. Here, we analysed the participation rate and the detection rate for cancer or advanced adenoma (advanced neoplasia) of FIT among nonattendees for reduced-preparation CTC, full-preparation CTC and OC. Nonattendees were 1721 of 2395 (71.9%) eligible invitees in the reduced-preparation CTC group, 1818 of 2430 (74.8%) in the full-preparation CTC group and 883 of 1036 (85.2%) in the OC group. Participation rates for FIT were 20.2% (347/1721) in nonattendees for reduced-preparation CTC, 21.4% (389/1818) in nonattendees for full-preparation CTC and 25.8% (228/883) in nonattendees for OC. Differences between both CTC groups and the OC group were statistically significant (P⩽0.01), whereas the difference between reduced-preparation and full-preparation CTC groups was not statistically significant (P=0.38). The detection rate of FIT was not statistically significantly different among nonattendees for reduced-preparation CTC (0.9%; 3/347), nonattendees for full-preparation CTC (1.8%; 7/389) and nonattendees for OC (1.3%; 3/228) (P>0.05). Offering FIT to nonattendees for CTC or OC increases the overall participation in colorectal cancer screening and enables the detection of additional advanced neoplasia.

Does low-dose aspirin use for cardiovascular disease prevention reduce colorectal cancer deaths? A comparison of two cohorts in the Florence district, Italy.

Aspirin has been associated with reduced incidence and mortality of colorectal and a few other cancers. The aim of our paper was to study the effect of low-dose aspirin intake on cancer mortality in a population-based cohort study. The study included inhabitants of the Florence district (Italy) at the beginning of 2007. We considered two cohorts: patients who received prescriptions of low-dose aspirin for the whole year and patients who did not have any prescriptions over the same period. We followed the two cohorts until 31 December 2013. By linking with the Tuscany Mortality Registry, we analysed cause-specific mortality. We used a Cox semiparametric model to compare the mortality of the two cohorts. There was an 18% higher probability [hazard ratio (HR)=1.18, 95% confidence interval (CI): 1.12–1.23] for all causes of death among the cohort of aspirin users, almost completely caused by cardiovascular diseases (CVDs) (HR=1.39, 95% CI: 1.29–1.49). Colorectal cancer mortality was reduced by almost 30% (HR=0.71, 95% CI: 0.52–0.97). Death caused by major bleeding was 11% higher (HR=1.11, 95% CI: 0.86–1.44), but not statistically significant. Our results support the hypothesis that the use of low-dose aspirin for CVD prevention reduces colorectal cancer mortality. Given the growing ability to identify subgroups of individuals with an increased risk of developing cancer, further studies are needed to study the effectiveness of different cancer screening strategies tailored to these specific subgroups. Our study suggests the importance of focusing on this issue from the opposite perspective, that is, considering subgroups of individuals at decreased risk, such as the subgroup of individuals who take low-dose aspirin for CVD prevention. Thus, further assessments are needed to possibly identify subgroup-specific screening strategies that would be more effective than those developed for average-risk individuals.

What is the best screening strategy to detect advanced colorectal adenomas? Simulation from ongoing Italian screening experiences

AIMS AND BACKGROUND The best screening strategy for colorectal cancer is still debated. We simulated two screening strategies, namely flexible sigmoidoscopy (single episode) and immunological fecal occult blood test (FOBT) (five biennial rounds) and comparing their results as regards advanced adenomas and colorectal cancer detection. METHODS A Markov model was developed to estimate the number of advanced adenomas and colorectal cancer detected with the two compared screening strategies. Two different scenarios, namely a) where the same compliance (50%) at both flexible sigmoidoscopy and immunological FOBT invitation is applied, and b) where the actual compliance observed at a national level (immunological FOBT, 45%; flexible sigmoidoscopy, 30%) is applied. RESULTS In scenario a), immunological FOBT would detect a total of 20,573 adenomas and 3,952 colorectal cancers, performing 74,507 total colonoscopies compared to 20,939 and 2,511, respectively, detected by flexible sigmoidoscopy, with 17,985 total colonoscopies. In scenario b), immunological FOBT would detect 17,845 advanced adenomas with 65,215 colonoscopies performed compared to 12,672 detected by flexible sigmoidoscopy with 10,796 colonoscopies. The probability of having a colonoscopy for a subject attending all the five immunological FOBT rounds was 15.9%. CONCLUSIONS The simulation suggests that also immunological FOBT screening may achieve a substantial detection of advanced adenomas and therefore may have an impact on colorectal cancer incidence.