Long-Term Follow-up of the Italian Flexible Sigmoidoscopy Screening Trial.

BACKGROUND: Recent reports showed that the protective effect of flexible sigmoidoscopy (FS) screening was maintained up to17 years, although differences were reported by sex. OBJECTIVE: To assess long-term reduction of colorectal cancer (CRC) incidence and mortality after a single FS screening. DESIGN: Parallel randomized controlled trial. (ISRCTN registry number: 27814061). SETTING: 6 centers in Italy. PARTICIPANTS: Persons aged 55 to 64 years expressing interest in having FS screening if invited, recruited from 1995 to 1999 and followed until 2012 (incidence) and 2014 to 2016 (mortality). INTERVENTION: Eligible persons were randomly assigned (1:1 ratio) to either the once-only FS screening group or control (usual care) group. MEASUREMENTS: Incidence and mortality rate ratios (RRs) and rate differences. RESULTS: A total of 34 272 persons (17 136 in each group) were included in the analysis; 9911 participants had screening in the intervention group. Median follow-up was 15.4 years for incidence and 18.8 years for mortality. Incidence of CRC was reduced by 19% (RR, 0.81 [95% CI, 0.71 to 0.93]) in the intention-to-treat (ITT) analysis, comparing the intervention with the control group, and by 33% (RR, 0.67 [CI, 0.56 to 0.81]) in the per protocol (PP) analysis, comparing participants screened in the intervention group with the control persons. Colorectal cancer mortality was reduced by 22% (RR, 0.78 [CI, 0.61 to 0.98]) in the ITT analysis and by 39% (RR, 0.61 [CI, 0.44 to 0.84]) in the PP analysis. Incidence of CRC was statistically significantly reduced among both men and women. Colorectal cancer mortality was statistically significantly reduced among men (ITT RR, 0.73 [CI, 0.54 to 0.97]) but not among women (ITT RR, 0.90 [CI, 0.59 to 1.37]). LIMITATION: Self-selection of volunteers from the general population sample targeted for recruitment may limit generalizability. CONCLUSION: The strong protective effect of a single FS screening for CRC incidence and mortality was maintained up to 15 and 19 years, respectively. PRIMARY FUNDING SOURCE: Italian Association for Cancer Research, Italian National Research Council, Istituto Oncologico Romagnolo, Fondo "E. Tempia," University of Milan, and Local Health Unit ASL-Torino.

Faecal haemoglobin concentration among subjects with negative FIT results is associated with the detection rate of neoplasia at subsequent rounds: a prospective study in the context of population based screening programmes in Italy.

OBJECTIVE: To estimate the predictive role of faecal haemoglobin (f-Hb) concentration among subjects with faecal immunochemical test (FIT) results below the positivity cut-off for the subsequent risk of advanced neoplasia (AN: colorectal cancer-CRC-or advanced adenoma). DESIGN: Prospective cohort of subjects aged 50-69 years, undergoing their first FIT between 1 January 2004 and 31 December 2010 in four population-based programmes in Italy. METHODS: All programmes adopted the same analytical procedure (OC Sensor, Eiken Japan), performed every 2 years, on a single sample, with the same positivity cut-off (20 µg Hb/g faeces). We assessed the AN risk at subsequent exams, the cumulative AN detection rate (DR) over the 4-year period following the second FIT and the interval CRC (IC) risk following two negative FITs by cumulative amount of f-Hb concentration over two consecutive negative FITs, using multivariable logistic regression models and the Kaplan-Meier method. RESULTS: The cumulative probability of a positive FIT result over the subsequent two rounds ranged between 7.8% (95% CI 7.5 to 8.2) for subjects with undetectable f-Hb at the initial two tests (50% of the screenees) and 48.4% (95% CI 44.0 to 53.0) among those (0.7% of the screenees) with a cumulative f-Hb concentration ≥20 µg/g faeces. The corresponding figures for cumulative DR were: 1.4% (95% CI 1.3 to 1.6) and 25.5% (95% CI 21.4 to 30.2) for AN; 0.17% (95% CI 0.12 to 0.23) and 4.5% (95% CI 2.8 to 7.1) for CRC. IC risk was also associated with cumulative f-Hb levels. CONCLUSION: The association of cumulative f-Hb concentration with subsequent AN and IC risk may allow to design tailored strategies to optimise the utilisation of endoscopy resources: subjects with cumulative f-Hb concentration ≥20 µg/g faeces over two negative tests could be referred immediately for total colonoscopy (TC), while screening interval might be extended for those with undetectable f-Hb.

Appropriateness of endoscopic surveillance recommendations in organised colorectal cancer screening programmes based on the faecal immunochemical test.

OBJECTIVES: To assess the appropriateness of recommendations for endoscopic surveillance in organised colorectal cancer (CRC) screening programmes based on the faecal immunochemical test (FIT). DESIGN: 74 Italian CRC screening programmes provided aggregated data on the recommendations given after FIT-positive colonoscopies in 2011 and 2013. Index colonoscopies were divided into negative/no adenoma and low- risk, intermediate-risk and high-risk adenomas. Postcolonoscopy recommendations included a return to screening (FIT after 2 years or 5 years), an endoscopic surveillance after 6 months or after 1 year, 3 years or 5 years, surgery or other. We assessed the deviation from the postcolonoscopy recommendations of the European Guidelines in 2011 and 2013 and the correlation between overuse of endoscopic surveillance in 2011 and the process indicators associated with the endoscopic workload in 2013. RESULTS: 49 704 postcolonoscopy recommendations were analysed. High-risk, intermediate-risk and low-risk adenomas, and no adenomas were reported in 5.9%, 19.3%, 15.3% and 51.5% of the cases, respectively. Endoscopic surveillance was inappropriately recommended in 67.4% and 7%, respectively, of cases with low-risk and no adenoma. Overall, 37% of all endoscopic surveillance recommendations were inappropriate (6696/17 860). Overuse of endoscopic surveillance was positively correlated with the extension of invitations (correlation coefficient (cc) 0.29; p value 0.03) and with compliance with post-FIT+ colonoscopy (cc 0.25; p value 0.05), while it was negatively correlated with total colonoscopy waiting times longer than 60 days (cc -0.26; p value 0.05). CONCLUSIONS: In organised screening programmes, a high rate of inappropriate recommendations for patients with low risk or no adenomas occurs, affecting the demand for endoscopic surveillance by a third.

Changes in cervical cancer incidence following the introduction of organized screening in Italy.

OBJECTIVE: To quantify the impact of organized cervical screening programs (OCSPs) on the incidence of invasive cervical cancer (ICC), comparing rates before and after activation of OCSPs. METHODS: This population-based investigation, using individual data from cancer registries and OCSPs, included 3557 women diagnosed with ICC at age 25-74years in 1995-2008. The year of full-activation of each OCSP was defined as the year when at least 40% of target women had been invited. Incidence rate ratios (IRRs) with 95% confidence intervals (95% CIs) were calculated as the ratios between age-standardized incidence rates observed in periods after full-activation of OCSPs vs those observed in the preceding quinquennium. RESULTS: ICC incidence rates diminished with time since OCSPs full-activation: after 6-8years, the IRR was 0.75 (95% CI: 0.67-0.85). The reduction was higher for stages IB-IV (IRR=0.68, 95% CI: 0.58-0.80), squamous cell ICCs (IRR=0.74, 95% CI: 0.64-0.84), and particularly evident among women aged 45-74years. Conversely, incidence rates of micro-invasive (stage IA) ICCs increased, though not significantly, among women aged 25-44years (IRR=1.34, 95% CI: 0.91-1.96). Following full-activation of OCSPs, micro-invasive ICCs were mainly and increasingly diagnosed within OCSPs (up to 72%). CONCLUSION(S): Within few years from activation, organized screening positively impacted the already low ICC incidence in Italy and favored down-staging.

Screening for colorectal cancer in Italy: 2011-2012 survey.

We present the main results of the 2011-2012 survey of the Italian screening programmes for colorectal cancer carried out by the National centre for screening monitoring (Osservatorio nazionale screening, ONS) on behalf of the Ministry of Health. By the end of 2012, 112 programmes were active, of which 11 had been activated during 2012 and 4 during 2011. The national theoretical extension increased from 66% of Italians aged 50-69 years residing in areas covered by organized screening programmes in 2010 to 73.7% in 2012. The majority of programmes employ the fecal immunochemical test (FIT), while some have adopted flexible sigmoidoscopy (FS) once in a lifetime and FIT for non-responders to FS. Overall, about 7,744,000 subjects were invited to undergo FIT, 53.1% of those to be invited within the two years. The adjusted attendance rate was 47.1%and 3,531,937 subjects were screened. Large differences in the attendance rate were observed among regions. Positivity rate of FIT programmes was 5.2% at first screening (range: 1.0-12.4%) and 4.0% at repeat screening (range: 3.4-6.4%). The average attendance rate to total colonoscopy (TC) was 81.2% and in two regions (Molise and Campania) it was lower than 70%. Completion rate for total colonoscopy (TC) was 91%. Among the 1,316,327 subjects attending screening for the first time, the detection rate (DR) per 1,000 screened subjects was 2.0 for invasive cancer and 9.1 ‰ for advanced adenomas (AA, adenomas with a diameter ≥1 cm, with villous/tubulo-villous type or high-grade dysplasia). As expected, the corresponding figures in the 2,215,610 subjects at repeat screening were lower (1.0‰ and 6.8‰ for invasive cancer and AA, respectively). Many programmes reported some difficulties in guaranteeing TC in the appropriate time frame to FIT+ subjects: in 15% of cases the waiting time was longer than two months. Ten programmes in 2011 and eight in 2012 employed FS as the screening test: 24,549 subjects were screened in the two years, with an attendance rate of 24.5%. Overall, 85.9% of FSs were classified as complete. Overall, TC referral rate was 9.8% and the DR per 1,000 screened subjects was 3.0 and 48.2 for invasive cancer and AA, respectively.

Hyperglycemia and microRNAs in prostate cancer.

BACKGROUND: Hyperglycemia can promote the development of prostate cancer (PCa). Differential expression levels of miRNAs between PCa patients and controls were also reported. Therefore, we examined the relationship between hyperglycemia and miRNA levels in PCa. METHODS: Relative expression of urinary miR-574-3p, miR-375, miR-205-5p, miR-200b-3p, miR-187-3p, miR-182-5p, and miR-100-5p were investigated in 105 PCa patients and 138 noncancer controls by Real-Time quantitative PCR. Fasting plasma glucose measurements were retrieved from clinical records. The differential miRNA expressions among groups were compared using non-parametric tests. Correlations with glucose and prostate-specific antigen (PSA) were tested using Pearson correlation coefficient. RESULTS: When we analyzed miRNA expression according to glycemic state, significant down-regulations were found for miR-200b-3p, miR-187-3p, miR-182-5p, and miR-100-5p in noncancer controls with high glucose. The lowest down-regulations were observed for miR-187-3p, miR-182-5p, and miR-100-5p. Subsequently, when hyperglycemia was considered in PCa, significant dysregulations of selected miRNAs were found in hyperglycemic PCa patients than in controls with high glucose. In particular, miR-375 and miR-182-5p showed a 3-FC in hyperglycemic PCa patients than controls who left hyperglycemia untreated. Conversely, only a down-regulation of miR-574-3p was observed in PCa patients regardless of glycemic status and only modest down-regulation of miR-574-3p, miR-200b-3p, miR-187-3p and miR-182-5p were found in normoglycemic PCa patients. Next, significant correlations between miRNAs and glucose (miR-200b-3p, miR-100-5p) and PSA (miR-205-5p and miR-187-3p) were detected in controls. Similarly, miR-205-5p and miR-187-3p were correlated with glucose in PCa patients, while miR-574-3p and miR-375 showed inverse relationships. CONCLUSIONS: miRNA dysregulations can occur in hyperglycemic PCa patients as compared to noncancer controls who left hyperglycemia untreated. Hyperglycemia can consistently promote the expression of miR-375 and miR-182-5p. Uncontrolled hyperglycemic state could contribute to the creation of a suitable microenvironment for later PCa development by promoting gene expression.

Screening patterns within organized programs and survival of Italian women with invasive cervical cancer.

OBJECTIVES: To evaluate screening patterns within organized cervical screening programs (OCSPs) and survival of women with invasive cervical cancer (ICC). METHODS: A population-based study was conducted in Italian areas covered by cancer registries and OCSPs. The study included all women aged 25-65 years diagnosed with ICC between 1995 and 2008, and their screening histories within OCSPs were retrieved. Hazard ratios (HR) of death and 95% confidence intervals (CI) were computed according to screening pattern, using Cox models adjusted for age, ICC stage, and major confounders. RESULTS: Among 3268 women with ICC, 20% were never-invited to OCSP, 36% were never-compliant with OCSP's invitation, 33% were compliant and had a screen-detected ICC within OCSP (i.e., after a positive cytology), and 11% were compliant but had a non-screen-detected ICC. Screen-detected ICCs were more frequently micro-invasive (42%) compared to non-screen-detected ones (14%). Compared to women with screen-detected ICC, the adjusted HRs of death were 1.9 (95% CI 1.5-2.4) for those never-invited, 2.0 (95% CI 1.6-2.5) for never-compliant, and 1.7 (95% CI 1.3-2.4) for compliant women having non-screen-detected ICC. CONCLUSION: Prolonged survival, beyond down-staging, of women with ICC detected within OCSPs in Italy, further calls for improvements of OCSPs' invitational coverage and participation.

The 5-year risk of recurrence of grade 2/3 cervical intraepithelial neoplasia after treatment in a population screening programme by human papillomavirus status: A cohort study in central Italy.

OBJECTIVES: (a) To estimate the risk of recurrent cervical intraepithelial neoplasia, grade 2/3 or worse (CIN2+/CIN3+), lesions within 5 years of follow-up in human papillomavirus-negative/human papillomavirus-positive cohorts; (b) to assess whether certain risk factors can predict the recurrence of CIN2+/CIN3+ lesions; and (c) to provide recommendations for follow-up after treatment of cervical intraepithelial neoplasia, grade 2/3 to prevent cervical cancer. SETTING: Organized cervical cancer screening programme in Central Italy. METHODS: We included 1063 consecutive first excisional treatments performed between 2006 and 2014 for screening-detected cervical intraepithelial neoplasia, grade 2/3 lesions among women aged 25-65. The study population was divided into two groups according to the human papillomavirus test results performed 6 months after treatment: Human papillomavirus-negative and human papillomavirus-positive cohorts. The 5-year risk of developing cervical intraepithelial neoplasia, grade 2/3 or worse (CIN2+/CIN3+) was estimated using the Kaplan-Meier method and the Cox regression model. RESULTS: Among 829 human papillomavirus-negative and 234 human papillomavirus-positive women, six (0.72%; three cervical intraepithelial neoplasia, grade 2, three cervical intraepithelial neoplasia, grade 3) and 45 (19.2%; 15 cervical intraepithelial neoplasia, grade 2, 30 cervical intraepithelial neoplasia, grade 3), respectively, developed CIN2+ recurrence within 5 years of follow-up. The cumulative risks for CIN2+ and CIN3+ were 0.9% (95% confidence interval: 0.4%-2.0%) and 0.5% (95% confidence interval: 0.1%-1.4%), respectively, for the human papillomavirus-negative cohort, and 24.8% (95% confidence interval: 18.5%-32.7%) and 16.9% (95% confidence interval: 11.4%-24.5%), respectively, for the human papillomavirus-positive cohort. Risk factors associated with increased risk of recurrence were both margins positive for the human papillomavirus-negative cohort, and positive margins, cervical intraepithelial neoplasia, grade 3 lesions, high-grade cytology and high viral load for the human papillomavirus-positive cohort. CONCLUSIONS: Human papillomavirus testing can identify women at increased risk of recurrence and this supports a recommendation for its use in the post-treatment follow-up of cervical intraepithelial neoplasia, grade 2/3 lesions.

The Consensus Project: Participation in cervical cancer screening by the first cohorts of girls offered HPV vaccination at age 15-16 years in Italy.

OBJECTIVE: To evaluate the association between human papillomavirus vaccination status and participation in cervical cancer screening (at age 25) by the first cohorts of girls who were offered vaccination at the age of 15 to 16 years in Italy. METHODS: Women born in 1993, 1994 and 1995 were invited to participate in cervical cancer screening between 2018 and 2020. We report participation in screening by vaccination status in three large areas, Florence province, Piedmont region and Savona province, where the Consensus Project was carried out. The relative risk of participation among vaccinated (≥2 doses) and unvaccinated women was estimated. Odds ratios (OR) of participation by vaccination status were estimated by logistic regression, adjusted by birthplace and birth cohort. RESULTS: Overall, 34,993 women were invited for screening: 13,006 (37.2%) participated and 10,062 of these agreed to participate in the Consensus intervention study. Among the invited women and screening participants, vaccinated women were 51.0% and 60.6%, respectively. Comparing vaccinated and unvaccinated women, the adjusted OR of screening participation was 1.80 (95% confidence interval (CI): 1.72-1.89), 2.17 (95% CI: 1.94-2.42), 1.59 (95% CI: 1.50-1.68) and 1.15 (95% CI: 0.86-1.54) for overall, Florence, Piedmont and Savona, respectively. About 33% of the invited women were unvaccinated and did not participate in screening: 25.8%, 59.5% and 64.2% of women born in Italy, in high migration pressure countries and in advanced development countries, respectively. CONCLUSIONS: Screening participation was higher among vaccinated than unvaccinated women. Active policies are needed to reduce inequalities, targeting the unscreened and unvaccinated population, particularly non-native women, to accelerate cervical cancer elimination in Italy.

[Screening for colorectal cancer in Italy, 2010 survey]. / Lo screening colorettale in Italia, survey 2010.

We present the main results of the 2010 survey of the Italian screening programmes for colorectal cancer carried out by the National centre for screening monitoring (Osservatorio nazionale screening, ONS) on behalf of the Ministry of health. By the end of 2010, 105 programmes were active, 9 of which had been activated during the year, and 65% of Italians aged 50-69 years were residing in areas covered by organised screening programmes (theoretical extension). Twelve regions had their whole population covered. In the South of Italy and Islands, 5 new programmes were activated in 2010, with a theoretical extension of 29%. The majority of programmes employed the faecal occult blood test (FIT), while some adopted flexible sigmoidoscopy (FS) once in a lifetime and FIT for non-responders to FS. Overall, about 3,404,000 subjects were invited to undergo FIT, 47.2% of those to be invited within the year. The adjusted attendance rate was 48% and approximately 1,568,796 subjects were screened. Large differences in the attendance rate were observed among regions: 10% of programmes reported values lower than 24%. Positivity rate of FIT programmes was 5.5% at first screening (range: 1.6-11.3%) and 4.3% at repeat screening (range: 3.2-6.7%). The average attendance rate to total colonoscopy (TC) was 81.4% and in one region it was lower than 70%. Completion rate for total colonoscopy (TC) was 88.7%. Among the 740,281 subjects attending screening for the first time, the detection rate (DR) per 1,000 screened subjects was 2.4 for invasive cancer and 10.3 for advanced adenomas (AA - adenomas with a diameter ≥1 cm, with villous/tubulo-villous type or with high-grade dysplasia). As expected, the corresponding figures in the 843,204 subjects at repeat screening were lower (1.2‰ and 7.6‰ for invasive cancer and AA, respectively). The DR of cancer and adenomas increased with age and was higher among males. Many programmes reported some difficulties in guaranteeing TC in the appropriate time frame to FIT+ subjects: in 16% of cases the waiting time was longer than two months. Nine programmes employed FS as the screening test: 98% of the target population (about 60,000 subjects) were invited, and 13,629 subjects were screened, with an attendance rate of 24%. Overall, 87% of FS were classified as complete. TC referral rate was 9.5% and the DR per 1,000 screened subjects was 2.8 and 40.6 for invasive cancer and AA, respectively.

Implementation of a centralized HPV-based cervical cancer screening programme in Tuscany: First round results and comparison with the foregoing Pap-based screening programme.

OBJECTIVE: To evaluate performance of the first round of HPV-based screening in Tuscany region and compare it with the prior round of Pap-based screening. SETTING: Tuscany region of Italy, where HPV-based cervical cancer screening started in 2013, with a strong level of centralization screening tests at the Regional Laboratory for Cancer Prevention (ISPRO). METHODS: The transition from Pap- to HPV-based screening was initiated for older women and at 3 out of 12 Tuscany Local Health Units (LHUs). Data from the Florence and Grosseto LHUs (about 300,000 women) were analysed and performance screening indicators estimated. RESULTS: HPV-based indicators recorded good performance, with increased compliance vs. the Pap-based programme. We registered a substantial decrease in waiting times from sampling to test reporting, probably related to the centralization strategy. Since the screening protocol was the same and conducted at a single laboratory, we could hypothesize that the difference in HPV positivity (6.8% in Florence vs. 8.4% in Grosseto) was due to a real difference in HPV prevalence among women of the two LHUs. The transition to HPV-based screening led to a significant increase both in colposcopy referral rate (4.3% vs. 1.2%) and CIN2+ detection rate (8.3‰ vs. 3.4‰). CONCLUSIONS: HPV-based is more effective in detecting high-grade precancerous and cancerous lesions than Pap-based screening and is characterized by an "anticipatory effect" in the detection of CIN2+ lesions. The transition from Pap-based to HPV-based screening programme should include increased resources dedicated to colposcopy services. Centralization in a laboratory with long experience in this field promotes efficiency of the screening process.

Screening for colorectal cancer in Italy, 2009 survey.

We present the main results of the sixth survey of the Italian screening programmes for colorectal cancer carried out by the National centre for screening monitoring (Osservatorio nazionale screening, ONS) on behalf of the Ministry of health. By the end of 2009, 98 programmes were active, of which 13 had been activated during the year, and 59% of Italians aged 50-69 years were residing in areas covered by organised screening programmes (theoretical extension). Eleven regions had their whole population covered. In the South of Italy and Islands, 4 new programmes were activated in 2009, with a theoretical extension of 22%. The majority of programmes employ the faecal occult blood test (FOBT), while some have adopted flexible sigmoidoscopy (FS) once in a lifetime and FOBT for non-responders to FS. Overall, about 2,935,000 subjects were invited to undergo FOBT, 40% of those to be invited within the year. The adjusted attendance rate was 50% and approximately 1,426,000 subjects were screened. Large differences in the attendance rate were observed among regions, with 10% of programmes reporting values lower than 29%. Positivity rate of FOBT programmes was 5.6% at first screening (range: 2.5-12.4%) and 4.2% at repeat screening (range: 2.5-7.3%). The average attendance rate to total colonoscopy (TC) was 82.5%and in one region it was lower than 70%. Completion rate for total colonoscopy (TC) was 91.2%. Among the 631,460 subjects attending screening for the first time, the detection rate (DR) per 1,000 screened subjects was 2.4 for invasive cancer and 11.6 for advanced adenomas (AA - adenomas with a diameter ≥ 1 cm, with villous/tubulo-villous type or with high-grade dysplasia). As expected, the corresponding figures in the 824,562 subjects at repeat screening were lower (1.3‰ and 7.6‰ for invasive cancer and AA, respectively). The DR of cancer and adenomas increased with age and was higher among males. Many programmes reported some difficulties in guaranteeing TC in the appropriate time frame to FOBT+ subjects: in 16% of cases the waiting time was longer than two months. Nine programmes employed FS as the screening test: 65% of the target population (about 60,000 subjects) were invited and 9 511 subjects were screened, with an attendance rate of 24.3%. Overall, 81% of FS were classified as complete. Overall TC referral rate was 11% and the DR per 1,000 screened subjects was 2.6 and 43.7 for invasive cancer and AA, respectively.

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 7days) and the time in the laboratory refrigerator before analysis (mean 4days). 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.

Screening for colorectal cancer in Italy: 2008 survey.

We present the main results from the fifth survey of the Italian screening programmes for colorectal cancer carried out by the National Centre for Screening Monitoring (Osservatorio Nazionale Screening, ONS) on behalf of the Ministry of Health. By the end of 2008, 87 programmes were active (14 had been activated during the year), and 52,9%of Italians aged 50- 69 years were residing in areas covered by organised screening programmes (theoretical extension). Ten Regions had their whole population covered. In the South of Italy and Islands, 12 new programmes were activated in 2008, including those of Abruzzo and Molise Regions, with an increase of theoretical extension from 7% to 21%. The majority of programmes employ the faecal occult blood test (FOBT), while some have adopted flexible sigmoidoscopy (FS) once in a lifetime, or a combination of both. Overall, about 2,593,000 subjects were invited to undergo FOBT, 71%of those to be invited within the year. The adjusted attendance rate was 47.5% and approximately 1,171,000 subjects were screened. Large differences in the attendance rate were observed among Regions, with 10% of programmes reporting values lower than 30%. Positivity rate of FOBT programmes was 5.9% at first screening (range 2.0-11%) and 4% at repeat screening (range 2.9-6.5%). The average attendance rate for total colonoscopy (TC) was 81.3% and in three Regions it was lower than 70%. Completion rate of TC was 92.2%. Among the 665,264 subjects attending screening for the first time, the detection rate (DR) per 1,000 screened subjects was 2.7 for invasive cancer and 13.1 for advanced adenomas (AA, adenomas with a diameter ≥1 cm, with villous/ tubulo-villous type or with high-grade dysplasia). As expected, the corresponding figures in the 552,391 subjects at repeat screening were lower (1.3‰ and 8.3‰ for invasive cancer and AA, respectively). The DR of cancer and adenomas increased with age and was higher among males. Many programmes reported some difficulties in guaranteeing TC in the appropriate time frame to FOBT+ subjects: in 16.0% of cases the waiting time was longer than two months. Seven programmes employed FS as the screening test: 58.8% of the target population (about 50,000 subjects) were invited and 8,135 subjects were screened, with an attendance rate of 27.2%. Overall, 83% of FS were classified as complete. Overall TC referral rate was 13.5% and the DR per 1,000 screened subjects was 4.7 and 47.5 for invasive cancer and AA, respectively.

Neonatal brain ultrasound training for beginners: Could a head phantom be useful?

BACKGROUND: The traditional method of teaching the technique of neonatal brain ultrasonography is based upon the interaction between the practitioner and the neonate under the supervision of a tutor. This approach has disadvantages in that it may result in a longer imaging examination and the patient may become agitated. As demand for ultrasound services escalates and departments get busier, this often means that the trainee and supervisor are under pressure to work rapidly. Such environments are common but not conducive to the development of adequate skills and competencies. A neonatal head phantom used as part of a dedicated study day could help the beginner to learn basic elements of the ultrasound examination within a safe stress-free environment. It offers the opportunity to repeat the examination as often as the trainee wishes without time pressures and the distraction of a moving and potentially very sick baby. AIM: The aim of this study is to evaluate the efficacy of a commercial phantom as a means for the practitioner to acquire the fundamental principles of neonatal brain ultrasound. METHOD: A total of 17 participants attending a one day neonatal ultrasound course aimed at beginners were invited to complete a short two-part questionnaire that assessed their perceived improvement in scanning ability before and after using a commercially available head phantom. RESULTS: Of the 14 returned questionnaires, the overall perceived understanding, ability and confidence improved and anxiety levels about the procedure fell. The median pre-training score was 9.0 compared with the median post-training score of 12.0 (P = 0.005, Wilcoxon signed-rank test). At least 79% (up to 86%) of participants valued their experience with the phantom and would recommend the course to colleagues. Furthermore, about two-thirds reported that they would like to have additional practise with the phantom. Preliminary data from this study suggest that beginners found the head phantom useful for mastering some of the early skills required for neonatal brain ultrasound examinations, which in turn improved their confidence and reduced anxiety.

Screening for colorectal cancer in Italy: 2007 survey.

We present the main results from the fourth survey of the Italian screening programmes for colorectal cancer carried out by the National Centre for Screening Monitoring (Osservatorio Nazionale Screeninng, ONS) on behalf of the Ministry of Health. During 2007, fi ve new programmes were activated, but three other programmes were stopped, including the regional programme of Basilicata, and by the end of the year 46.6% of Italians aged 50-69 years were residing in areas covered by organised screening programmes (theoretical extension). Seven regions had their whole population covered. In the South of Italy and Islands only one new programme was activated in 2007, while two others were stopped, with a decline of theoretical extension from 10% to 7%. The majority of programmes employ the faecal occult blood test (FOBT), while some have adopted flexible sigmoidoscopy (FS) once in a lifetime, or a combination of both. Overall, about 2,600,000 subjects were invited to undergo FOBT, 79.1% of those to be invited within the year. The adjusted attendance rate was 46.3% and approximately 1,131,900 subjects were screened. Large differences in the attendance rate were observed among Regions, with 10% of programmes reporting values lower than 33%. Positivity rate of FOBT programmes was 5.6% at first and 4% at repeat screening. The average attendance rate for total colonoscopy (TC) was 78.7% and in two Regions it was lower than 60%. Completion rate of TC was 91.6%. Among the 914,029 subjects attending screening for the first time, the detection rate (DR) per 1,000 screened subjects was 2.7 for invasive cancer and 12.2 for advanced adenomas (AA, adenomas with a diameter >/=1 cm, with villous/tubulovillous type or with high-grade dysplasia). As expected, the corresponding figures at repeat screening were lower. The DR of cancer and adenomas increased with age and was higher among males; 25% of screen-detected cancers were in TNM stage III+. Many programmes reported some difficulties in guaranteeing TC in the appropriate time frame to SOF+ subjects: in 23.9% of cases the waiting time was longer than two months. Seven programmes employed FS as the screening test: 66.5% of the target population (about 50,000 subjects) were invited and 8,678 subjects were screened, with an attendance rate of 27.7%. Overall, 88% of FS were classified as complete. Overall TC referral rate was 11.1% and the DR per 1,000 screened subjects was 4.4 and 58.4 for invasive cancer and AA, respectively.

Screening for colorectal cancer in Italy: 2006 survey.

We present the main results of the third survey of the Italian screening programmes for colorectal cancer carried out by the ONS (Osservatorio Nazionale Screening, National Centre for Screening Monitoring) on behalf of the Ministry of Health. During 2006, many new programmes were activated and by the end of the year, 44% of Italians aged 50-69 years were residing in areas covered by organised screening programmes (theoretical extension). Five regions had their entire population covered. In the South of Italy and Islands only one new programme was activated in 2006, with a 10% theoretical extension. The majority of programmes employ the faecal occult blood test (FOBT), while some have adopted the flexible sigmoidoscopy (PS) once in a lifetime, or a combination of both. Overall, about 2,107,000 subjects were invited to undergo FOBT, 70.3% of those to be invited within the year. The adjusted attendance rate was 44.6% and approximately 907,000 subjects were screened. Major differences in the attendance rate were observed among regions, with 10% of programmes reporting values lower than 26%. Positivity rate of FOBT programmes was 5.3% at first and 3.9% at repeat screening: it increased with age and was higher among males than females in all age groups. The average attendance rate to total colonoscopy (TC) was 81% (10th-9Oth percentiles: 64%, 93%). Completion rate of TC was 89%, with higher rates among males. At first screening, the detection rate (DR) per 1,000 screened subjects was 3.1 and 14.6 for invasive cancer and advanced adenomas (AA--adenomas with a diameter > or =1 cm, with villous/tubulo-villous type or with high-grade dysplasia), respectively; the corresponding figures at repeat screening were 1.3 per thousand for cancer and 7.7 per thousand for AA. The DR of cancer and adenomas increased with age and was higher among males; 25% of screen-detected cancers were in TNM stage III+. The positive predictive value (PPV) was 6.8% for cancer and 32.1% for AA at first screening, and 4.0% for cancer and 23.4% for AA at repeat screening. Given the high PPVof a positive FOBT, obtaining a high attendance at TC is therefore crucial. Seven programmes employed PS as the screening test: 51.4% of the target population (about 50,000 subjects) were invited and 7,589 subjects were screened, with an attendance rate of 29.2%. Overall, 88% of FS were classified as complete. TC referral rates ranged between 6.1 and 17.8%, due to different referral criteria. Among subjects referred to colonoscopy, the prevalence of proximal AA and cancer ranged from 6 to 18.2%. The overall DR (subjects with at least one advanced lesion) ranged from 4.9 to 7.5%. In conclusion, during 2006, organised colorectal cancer screening programmes in Italy grew considerably, covering almost half of the eligible population at a national level. Many programmes were activated in the second part of the year, thus their results should be evaluated with caution. However, reported experiences showed good results in terms of attendance and DR, although some critical aspects need to be carefully addressed when planning and implementing screening activity.

Screening for colorectal cancer in Italy: 2005 survey.

We present the main results from the second survey of the Italian screening programmes for colorectal cancer carried out by the National Centre for Screening Monitoring on behalf of the Ministry of Health. During 2005, 52 programmes, adopting faecal occult blood testing (FOBT), sigmoidoscopy (FS), or a combination of both, were active in Italy. Overall, 827,473 subjects were invited to FOBT and 376,240 were screened; the adjusted attendance rate (47.1%) equals the best performances reported in the literature. Positivity rate of FOBT programmes was 5.8% at first and 4.1% at repeat screening: it increased with age and was higher among males than females in all age groups. The average attendance rate to colonoscopy (TC) was 82% (range: 56%-100%). Completion rate of TC was 91%, with higher rates among males. At first screening, the detection rate (DR) per 1000 screened subjects was 3.7 and 16.8 for invasive cancer and advanced adenomas (AA) (adenomas with a diameter > or =1 cm, with villous/tubulo-villous type or with high-grade dysplasia) respectively; the corresponding figures at repeat screening were 1.1 for cancer and 4.9 for AA. The DR of cancer and adenomas increased with age and it was higher among males, 55% of screen-detected cancers were at TNM stage I. The positive predictive value (PPV) was 7.4% for cancer and 32.9% for AA at first screening, and 4.5% for cancer and 20.5% for AA at repeat screening. Given this high PPV of positive FOBT, to obtain a high attendance at TC is crucial. The six FS programmes invited almost half of their target population (about 40,000 subjects) and 5,821 subjects were screened, with an attendance rate of 29.1%. Overall 89.0% of FS were classified as complete. TC referral rates ranged between 7.7 and 13.8%, due to different referral criteria. Among subjects referred to colonoscopy the prevalence of proximal AA and cancer ranged from 5.4 to 11.1%. The overall DR (subjects with at least one advanced lesion) ranged from 3.5 to 7.0%. In conclusion, during 2005 the organised programmes for colorectal cancer screening in Italy increased considerably, covering about one third of the eligible population at a national level. Many programmes were activated in the second part of the year, thus their results have to be evaluated with caution. However, the reported experiences showed good results in terms of attendance and DR, although some critical aspects need to be carefully addressed when planning and implementing screening activity.

Cervical cancer screening in immigrant women in Italy: a survey on participation, cytology and histology results.

Cervical cancer screening programmes in Italy actively invite all 25-64-year-old resident women for the Pap test every 3 years irrespective of their citizenship. Immigrant women come from countries where screening is absent or poorly implemented and the prevalence of human papillomavirus is often high. These women therefore have significant risk factors for cervical cancer. The Italian Group for Cervical Cancer Screening promoted a survey of all the screening programmes on the participation and the positivity and detection rates in Italian and foreign women in 2009-2011. Aggregated data for participation, cytology results, compliance with colposcopy and histology results were collected, distinguishing between women born in Italy and abroad. All comparisons were age adjusted. Forty-eight programmes out of 120 participated in the immigrant survey, with 3 147 428 invited and 1 427 412 screened Italian women and 516 291 invited and 205 948 screened foreign women. Foreign women had a slightly lower participation rate compared with Italians (39.9 vs. 45.4%), whereas compliance with colposcopy was similar (90%). Foreigners showed a higher risk of pathological findings than Italians: cytology positivity [relative risk (RR)=1.25, 95% confidence interval (CI) 1.24-1.27] and detection rate for cervical intraepithelial neoplasia grade 2 (CIN2) (RR=1.39, 95% CI 1.31-1.47), CIN3 (RR=2.07, 95% CI 1.96-2.18) and cancer (RR=2.68, 95% CI 2.24-3.22). The ratio between cancer and CIN was higher in immigrants (0.06 vs. 0.04, P<0.01). Foreign women had a higher risk of cervical precancer and cancer. Because of their high risk and because opportunistic screening does not cover this often disadvantaged group, achieving high participation in screening programmes for foreigners is critical to further reducing the cervical cancer burden in Italy.

Participation and risk of high grade cytological lesions among immigrants and Italian-born women in an organized cervical cancer screening program in Central Italy.

Few studies analyzed the risk for high-grade squamous intraepithelial lesions or worse (HSIL+) among immigrants and natives attending organized cervical cancer (CC) screening programs (SP). We evaluated participation and diagnosis of HSIL+ by country of birth with logistic models. Overall 540,779 invitation letters were delivered to target women of Florence SP in three screening rounds (years 2000-2002, 2003-2005, 2006-2008). The probability of attending screening was lower for immigrants than natives, but the difference decreased from 35% (1st round) to 20% (2nd-3rd round) for women born in high migration pressure (HMP) countries. The risk of HSIL+ was double than natives for HMP-born women from countries with high prevalence of human papillomavirus, even adjusting for age and previous history of Pap test. This is an important public health problem due to an increasing proportion over time of immigrant women with a lower attendance and greater risk for CC.