Baldness and testicular cancer: the EPSAM case-control study.

The etiology of testicular cancer is largely unexplained. Research has mainly focused on prenatal exposures, especially to sex hormones, while less attention has been paid to exposures that may act also postnatally. As baldness has been previously associated with testicular cancer risk we focused on baldness and body hairiness, which are both associated with androgen activity. We used data of the Postnatal Exposures and Male Health (EPSAM) study, a case-control study on testicular cancer conducted in the Province of Turin, Italy, involving cases diagnosed between 1997 and 2008. Information was collected using mailed questionnaires. Analyses included 255 cases and 459 controls. We calculated ORs and 95% CIs to estimate testicular cancer risk among those who developed baldness and among those with body hairiness. We found an inverse association between testicular cancer and baldness (OR: 0.67, 95% CI: 0.46-0.98) and body hairiness (OR: 0.78, 95% CI: 0.53-1.16), although the latter had wider CIs. The inverse association between baldness and testicular cancer is consistent with the results from previous studies. These results suggest that androgens activity may influence testicular cancer risk.

A phase-III prevention trial of low-dose tamoxifen in postmenopausal hormone replacement therapy users: the HOT study.

BACKGROUND: Postmenopausal hormone replacement therapy (HRT) relieves menopausal symptoms and may decrease mortality in recently postmenopausal women, but increases breast cancer risk. Low-dose tamoxifen has shown retained activity in phase-II studies. METHODS: We conducted a phase-III trial in 1884 recently postmenopausal women on HRT who were randomly assigned to either tamoxifen, 5 mg/day, or placebo for 5 years. The primary end point was breast cancer incidence. RESULTS: After 6.2 ± 1.9 years mean follow-up, there were 24 breast cancers on placebo and 19 on tamoxifen (risk ratio, RR, 0.80; 95% CI 0.44-1.46). Tamoxifen showed favorable trends in luminal-A tumors (RR, 0.32; 95% CI 0.12-0.86), in HRT users <5 years (RR, 0.35; 95% CI 0.15-0.82) and in women completing at least 12 months of treatment (RR, 0.49; 95% CI 0.23-1.02). Serious adverse events did not differ between placebo and tamoxifen, including, respectively, coronary heart syndrome (6 versus 4), cerebrovascular events (2 versus 5), VTE (2 versus 5) and uterine cancers (3 versus 1). Vasomotor symptoms were 50% more frequent on tamoxifen. CONCLUSIONS: The addition of low-dose tamoxifen to HRT did not significantly reduce breast cancer risk and increased climacteric symptoms in recently postmenopausal women. However, we noted beneficial trends in some subgroups which may deserve a larger study.

Stratified cancer screening: the practicalities of implementation.

BACKGROUND: Improving understanding of the genetic basis of disease susceptibility enables us to estimate individuals' risk of developing cancer and offer them disease prevention, including screening, stratified to reflect that risk. Little attention has so far been given to the implementation of stratified screening. This article reviews the issues that would arise in delivering such tailored approaches to prevention in practice. RESULTS: Issues analysed include the organisational context within which implementation of stratified prevention would occur, how the offer of screening would be made, making sure consent is adequately informed, how individuals' risk would be assessed, the age at which risk estimation should occur, and the potential use of genetic data for other purposes. The review also considers how management might differ depending on individuals' risk, how their results would be communicated and their follow-up arranged, and the different issues raised by modification of an existing screening programme, such as that for breast cancer, and the establishment of a new one, for example for prostate cancer. CONCLUSION: Stratified screening based on genetic testing is a radically new approach to prevention. Various organisational issues would need to be considered before it could be introduced, and a number of questions require further research.

European guidelines for quality assurance in colorectal cancer screening and diagnosis: overview and introduction to the full supplement publication.

Population-based screening for early detection and treatment of colorectal cancer (CRC) and precursor lesions, using evidence-based methods, can be effective in populations with a significant burden of the disease provided the services are of high quality. Multidisciplinary, evidence-based guidelines for quality assurance in CRC screening and diagnosis have been developed by experts in a project co-financed by the European Union. The 450-page guidelines were published in book format by the European Commission in 2010.  They include 10 chapters and over 250 recommendations, individually graded according to the strength of the recommendation and the supporting evidence. Adoption of the recommendations can improve and maintain the quality and effectiveness of an entire screening process, including identification and invitation of the target population, diagnosis and management of the disease and appropriate surveillance in people with detected lesions. To make the principles, recommendations and standards in the guidelines known to a wider professional and scientific community and to facilitate their use in the scientific literature, the original content is presented in journal format in an open-access Supplement of Endoscopy. The editors have prepared the present overview to inform readers of the comprehensive scope and content of the guidelines.

European guidelines for quality assurance in colorectal cancer screening and diagnosis. First Edition--Executive summary.

Multidisciplinary, evidence-based guidelines for quality assurance in colorectal cancer screening and diagnosis have been developed by experts in a project coordinated by the International Agency for Research on Cancer. The full guideline document covers the entire process of population-based screening. It consists of 10 chapters and over 250 recommendations, graded according to the strength of the recommendation and the supporting evidence. The 450-page guidelines and the extensive evidence base have been published by the European Commission. The content of the executive summary is presented here to promote international discussion and collaboration by making the principles and standards recommended in the new EU Guidelines known to a wider professional and scientific community. Following these recommendations has the potential to enhance the control of colorectal cancer through improvement in the quality and effectiveness of screening programmes and services.

European guidelines for quality assurance in colorectal cancer screening and diagnosis. First Edition--Colonoscopic surveillance following adenoma removal.

Multidisciplinary, evidence-based guidelines for quality assurance in colorectal cancer screening and diagnosis have been developed by experts in a project coordinated by the International Agency for Research on Cancer. The full guideline document covers the entire process of population-based screening. It consists of 10 chapters and over 250 recommendations, graded according to the strength of the recommendation and the supporting evidence. The 450-page guidelines and the extensive evidence base have been published by the European Commission. The chapter on colonoscopic surveillance following adenoma removal includes 24 graded recommendations. The content of the chapter is presented here to promote international discussion and collaboration by making the principles and standards recommended in the new EU Guidelines known to a wider professional and scientific community. Following these recommendations has the potential to enhance the control of colorectal cancer through improvement in the quality and effectiveness of surveillance and other elements in the screening process, including multi-disciplinary diagnosis and management of the disease.

European guidelines for quality assurance in colorectal cancer screening and diagnosis. First Edition--Principles of evidence assessment and methods for reaching recommendations.

Multidisciplinary, evidence-based guidelines for quality assurance in colorectal cancer screening and diagnosis have been developed by experts in a project coordinated by the International Agency for Research on Cancer. The full guideline document covers the entire process of population-based screening. It consists of 10 chapters and over 250 recommendations, graded according to the strength of the recommendation and the supporting evidence. The 450-page guidelines and the extensive evidence base have been published by the European Commission. The principles of evidence assessment and methods for reaching recommendations are presented here to promote international discussion and collaboration by making the principles and methods used in developing the guidelines known to a wider professional and scientific community. Following this methodology in the future updating of the guidelines has the potential to enhance the control of colorectal cancer through improvement in the quality and effectiveness of the screening process, including multidisciplinary diagnosis and management of the disease.

Assessment of the multiple components of the variability in the adenoma detection rate in sigmoidoscopy screening, and lessons for training.

BACKGROUND AND STUDY AIMS: The determinants of the observed variability of adenoma detection rate (ADR) in endoscopy screening have not yet been fully explained. PATIENTS AND METHODS: Between November 1999 and November 2006 13 764 people (7094 men, 6670 women; age range 55-64) underwent screening flexible sigmoidoscopy at five hospital endoscopy units in Turin. To study the determinants of the ADR for distal adenomas, accounting for patient, examiner, and hospital characteristics, we applied a multivariate multilevel regression model. RESULTS: Average ADRs for all adenomas and for advanced adenomas (size > or = 10 mm, villous component > 20 %, high grade dysplasia) were 13.5 % (range 5.2 %-25.0 %) and 6.4 % (3.1 %-10.7 %) for men, and 8.0 % (2.5 %-14.0 %) and 3.7 % (0.2 % - 7.4 %) for women. In multivariate analysis, increased ADR of advanced adenomas was associated with male gender (odds ratio [OR] 1.78, 95 %CI 1.49 - 2.11), self-report of one first-degree relative with colorectal cancer (CRC) (1.44, 1.11-1.86), or of recent-onset rectal bleeding (1.73, 1.24-2.40). Adjusting for these variables, a significantly lower ADR was found for endoscopists with either a lower rate of incomplete sigmoidoscopy (< 9 %; OR 0.59, 95 %CI 0.41-0.87) or a higher rate (> 12 %; 0.64, 0.45-0.91), or with low activity volume (< 85 sigmoidoscopies/year; 0.66, 0.50-0.86). Residual variability explained by the endoscopy center effect was about 1 % and statistically significant. CONCLUSIONS: Endoscopist performance in flexible sigmoidoscopy CRC screening is highly variable. Low volume of screening activity independently predicts lower ADR, suggesting that operators devoting more time to screening sigmoidoscopy may perform better. Variability among pathologists in adenoma classification might explain part of the residual variability across endoscopy units.

European Guidelines for Quality Assurance in Cervical Cancer Screening. Second edition--summary document.

European Guidelines for Quality Assurance in Cervical Cancer Screening have been initiated in the Europe Against Cancer Programme. The first edition established the principles of organised population-based screening and stimulated numerous pilot projects. The second multidisciplinary edition was published in 2008 and comprises approximately 250 pages divided into seven chapters prepared by 48 authors and contributors. Considerable attention has been devoted to organised, population-based programme policies which minimise adverse effects and maximise benefits of screening. It is hoped that this expanded guidelines edition will have a greater impact on countries in which screening programmes are still lacking and in which opportunistic screening has been preferred in the past. Other methodological aspects such as future prospects of human papillomavirus testing and vaccination in cervical cancer control have also been examined in the second edition; recommendations for integration of the latter technologies into European guidelines are currently under development in a related project supported by the European Union Health Programme. An overview of the fundamental points and principles that should support any quality-assured screening programme and key performance indicators are presented here in a summary document of the second guidelines edition in order to make these principles and standards known to a wider scientific community.

Appropriateness of early breast cancer management in relation to patient and hospital characteristics: a population based study in Northern Italy.

Administrative data may provide valuable information for monitoring the quality of care at population level and offer an efficient way of gathering data on individual patterns of care, and also to shed light on inequalities in access to appropriate medical care. The aim of the study was to investigate the role of patient and hospital characteristics in the initial treatment of early breast cancer using administrative data. Incident breast cancer patients were identified from hospital discharge records and linked to the radiotherapy outpatient database during 2000-2004 in the Piedmont region of Northwestern Italy. Women treated with breast-conserving surgery followed by radiotherapy (BCS + RT) were compared to those treated with BCS without radiotherapy (BCS w/o RT) or mastectomy using multinomial logistic regression models. Out of 16,022 incident cases, 46.2% received BCS + RT, 20.3% received BCS w/o RT, and 33.5% received a mastectomy. Compared to BCS + RT, the factors associated with BCS w/o RT were: increased age (OR = 1.54; 95% CI = 1.29-1.85, for ages 70-79 vs. <50), being unmarried (1.24; 1.13-1.36), presence of co-morbidities (1.32; 1.10-1.58), being treated at hospitals with low surgical volume (1.31; 1.07-1.60 for hospitals with less than 50 vs. > or =150 interventions/year), and living far from radiotherapy facilities (1.75; 1.39-2.20 for those at a distance of >45 min). These same factors were also associated with mastectomy. During the 5-year period observed, there was a trend of reduced probability of receiving a mastectomy (0.70; 0.56-0.88 for 2004 vs. 2000). The presence or absence of nodal involvement was positively associated with mastectomy (2.28; 1.83-2.85) and negatively associated with BCS w/o RT (0.65; 0.56-0.76). After adjustment for potential confounders, education level did not show any association with the type of treatment. Social and geographical factors, in addition to hospital specialization, should be considered to reduce inappropriateness of care for breast cancer.

Do women >or=50 years of age need as much screening as women <50 years after they have had negative screening results?

To assess the adequacy of a routine screening to identify cervical intraepithelial neoplasia 2 or worse (CIN2+) in women over 50 years of age, a retrospective cohort was set in six Italian organised population-based screening programmes. In all, 287 330 women (1 714 550 person-years of observation, 1110 cases) screened at age 25-64, with at least two cytological screening tests, the first negative, were followed from their first negative smear until a biopsy proven CIN2+ lesion or their last negative smear. For women aged 25-49 and 50-64 years, crude and age-standardised detection rate (DR), cumulative risk (CR), adjusted hazard risk for number of previous negative screens, probability of false-positive CIN2+ after two or more smear tests were calculated. Detection rate is significantly lower over 50 years of age. Multivariable analysis shows a significant protective effect from four screening episodes (DR=0.70, 95% CI: 0.51-0.97); the effect of age >or=50 is 0.29 (95% CI: 0.24-0.35). The CR of CIN2+ is at least eightfold higher in women <50 (CR=2.06, 95% CI: 1.88-2.23) after one previous negative test than in women >or=50 years with four screens (CR=0.23, 95% CI: 0.00-0.46). Over 50 years of age, after four tests at least three false-positive cases are diagnosed for every true positive. Benefits arising from cytological screening is uncertain in well-screened older women.

Effectiveness of service screening: a case-control study to assess breast cancer mortality reduction.

The aim of this study was the evaluation of the impact of service screening programmes on breast cancer mortality in five regions of Italy. We conducted a matched case-control study with four controls for each case. Cases were defined as breast cancer deaths occurred not later than 31 December 2002. Controls were sampled from the local municipality list and matched by date of birth. Screening histories were assessed by the local, computerised, screening database and subjects were classified as either invited or not-yet-invited and as either screened or unscreened. There were a total of 1750 breast cancer deaths within the 50 to 74-year-old breast cancer cases and a total of 7000 controls. The logistic conditional estimate of the cumulative odds ratios comparing invited with not-yet-invited women was 0.75 (95% CI: 0.62-0.92). Restricting the analyses to invited women, the odds ratio of screened to never-respondent women corrected for self-selection bias was 0.55 (95% CI: 0.36-0.85). The introduction of breast cancer screening programmes in Italy is associated with a reduction in breast cancer mortality attributable to the additional impact of service screening over and above the background access to mammography.

Impact of the introduction of organised screening for cervical cancer in Turin, Italy: cancer incidence by screening history 1992-98.

After an organised cervical screening programme was introduced in Turin in 1992, the age-adjusted cervical cancer incidence ratio in 1992-98 was 0.81 (95% confidence interval (CI) 0.59-1.09) for invited vs not invited women and 0.25 (95% CI 0.13-0.50) for attenders vs non attenders. An organised screening programme can further reduce cervical cancer incidence in an area where substantial spontaneous activity was previously present.

Monitoring surgical treatment of screen-detected breast lesions in Italy.

The object of this study was to assess quality of care and adherence to treatment guidelines of screen-detected lesions in Italy using a new audit system. Data on screen-detected cases surgically treated in 1997 were collected using a system (QT 2.3) developed within the Italian Group for Planning and Evaluating Mammographic Screening Programmes (GISMa) and the European Breast Cancer Screening Network. Results of 18 performance parameters were considered compared with the reference standards. In 1997, 515 lesions (335 invasive, 60 in situ and 120 benign) in 496 patients were collected from 14 departments in the Central and Northern area of Italy. The 18 indicators were analysed and grouped according to six quality objectives. Some results were good and others were excellent, such as intraoperative identification, breast conservation surgery, adequate axillary procedures and completeness of pathology reports, but most of them failed: waiting times, preoperative diagnosis, employment of frozen section on small lesions and avoiding axillary procedures in ductal carcinoma-in-situ. This work is a first attempt in Italy to evaluate and uniform the criteria adopted for quality control of breast cancer treatment, using a standardised system. Some results are good or excellent, the overall level of compliance with quality indicators is not satisfactory and corrective actions should be undertaken for a number of issues. A continuous monitoring should be performed and appropriate action taken in order to verify the effectiveness of the corrective actions and to provide screen-detected patients with the best quality of care.

Predictive value of rectal bleeding for distal colonic neoplastic lesions in a screened population.

The aim of this study was to determine the diagnostic value of rectal bleeding for distal colorectal cancer (CRC), or large (> or =10 mm) adenomas among an average-risk population. A cross-sectional survey was conducted among individuals aged 55-64 years, who attended sigmoidoscopy (FS) screening in the context of a multicentre randomised trial of FS screening for CRC. Sensitivity, specificity and positive predictive value (PPV) of rectal bleeding for large distal adenomas or CRC were calculated. Rectal bleeding was reported by 8.8% of 8507 patients examined (15% of those with large adenomas and 29% of those with CRC). The risk of CRC was increased when bleeding was associated with an altered bowel habit: odds ratio (OR)=10.42; 95% Confidence Interval (CI): 4.08-26.59; the corresponding OR for isolated bleeding was 5.29 (95% CI: 2.28-12.30). Rectal bleeding carries an increased risk of distal neoplastic lesions. However, most lesions are detected among asymptomatic subjects. This finding suggests that screening represents the optimal strategy to detect CRC or large adenomas in the distal colon in the targeted age range.

The impact of organised screening programmes on the stage-specific incidence of breast cancer in some Italian areas.

The aim of this study was to examine the effects of mammographic screening programmes on stage-specific incidence of breast cancer. The study compared prescreening and screening periods in seven areas in Italy, primarily evaluating the first screening round. All 17617 breast cancers (16554 invasive, 1063 in situ) registered in women aged 40-79 years between 1988 and 1999 were analysed through age-standardised rates and Poisson regression models. For all areas, independent of the baseline rates, the introduction of screening increased incidence for invasive cancers overall and, more markedly, for early cancers (screening/prescreening ratio: range 1.07-1.47 and 1.23-1.82, respectively), modifying the pattern of age-specific rates. The multiple regression analysis showed that the percentage of cases diagnosed at screening explained most of the increase; a residual effect of diagnosis period (screening versus prescreening) suggested a role for 'spontaneous' early detection in ages outside of the screening programme. Advanced cases did not show consistent variations across the registries for those aged 40-79 years (range: 0.91-1.21), whereas a more coherent picture was observed for those aged 50-69 years. In one area, a moderate reduction in the number of 'advanced' cases in the second screening period was observed. For all stages, the age-specific incidence rates of cases diagnosed outside of the screening programme for the age groups 50-69 years were lower than the corresponding rates in the prescreening period, suggesting a shift from the usual clinical services to the screening programme. Our results confirmed the increase in early-stage cancers occurring at the start of screening, and substantially explained the rise in breast cancer incidence. In addition, our study confirms the importance of cancer registries in monitoring the effect of breast cancer screening and the validity, for this purpose, of the linkage between cancer registries and screening programme databases.

Effect of circulation and discussion of cervical smears on agreement between laboratories.

The study objective was assessing whether circulation of smears and discussion of those with differing interpretation can increase reproducibility between laboratories. The study included: the blind interpretation of a first set of 194 smears among seven laboratories, the discussion of smears with discrepant diagnoses during the previous phase and the blind interpretation of a second set of smears of same size and characteristics. After discussions, the overall weighted kappa increased in five laboratories (substantially in three : +50%, +27% and +20%). However, no change was observed in one laboratory and a slight decrease (-4%) in another. The latter interpreted the second set of smears at a longer time interval from discussions. Agreement improved for all diagnostic classes except low grade intraepithelial neoplasia (LSIL). Overall, the intervention increased diagnostic agreement, but its effect varied with laboratory and by diagnostic class and could be transient. Continued programmes of smear exchange and discussion appear to be advisable.