Colorectal cancer after a negative Haemoccult II® test and programme sensitivity after a first round of screening: the experience of the Department of Calvados (France)

Colorectal cancers emerging after a negative Haemoccult II® are described in the context of a first round of mass screening in the Department of Calvados (France), from April 1991 to the end of December 1994. People with a cancer occurring after a negative test until 31 December 1995 were identified by a local cancer registry. Incidence was calculated and the programme sensitivity was estimated. The incidence of cancer emerging after a negative test was 57.7 per 100 000, i.e. half of the calculated incidence in the reference group (141.6 per 100 000). These cancers did not differ from those of either the non-responder or reference groups, in particular for the stage of extension. The programme sensitivity was globally higher than that estimated in European trials: 77.2, 66.3 and 55.9%, 1, 2 and 3 years after the test respectively. Programme sensitivity was higher for distal colon cancer 1 year after the test, which is probably due to the relatively slow growth of this subsite. © 1999 Cancer Research Campaig

What should the detection rates of cancers be in breast screening programmes?

Minimum detection rates at screening are sometimes laid down as standards for breast cancer screening programmes, based on underlying incidence of the disease in the age group screened. Detection rates should also depend on desired sensitivity, mean sojourn time, interscreening interval and the screening round – that is, prevalent (first) or incident (second or subsequent). In this paper, we use these quantities to derive expected, minimum and maximum detection rates proportional to the underlying incidence as well as estimated underlying incidence rates from extrapolation of prescreening trends in England and Wales to derive alternative standard minimum, expected and maximum detection rates per 1000 women screened for the UK Breast Screening Programme, as follows: minimum detection rates should be 4.1 and 4.3 at prevalence screen and incidence screens, respectively; expected rates should be 6.9 and 4.8 and maximum rates of 9.6 and 5.5. These are consistent with observed detection rates in the UK programme

Bowel cancer screening in England: a qualitative study of GPs' attitudes and information needs

BACKGROUND: The National Health Service Bowel Cancer Screening Programme is to be introduced in England during 2006. General Practitioners are a potentially important point of contact for participants throughout the screening process. The aims of the study were to examine GPs' attitudes and information needs with regard to bowel cancer screening, with a view to developing an information pack for primary care teams that will be circulated prior to the introduction of the programme. METHODS: 32 GPs participated in semi-structured telephone interviews. 18 of these had participated in the English Bowel Screening Pilot, and 14 had not. Interviews covered attitudes towards the introduction of the Bowel Cancer Screening Programme, expected or actual increases in workload, confidence in promoting informed choice, and preferences for receiving information about the programme. RESULTS: GPs in the study were generally positive about the introduction of the Bowel Cancer Screening Programme. A number of concerns were identified by GPs who had not taken part in the pilot programme, particularly relating to patient welfare, patient participation, and increased workload. GPs who had taken part in the pilot reported holding similar concerns prior to their involvement. However, in many cases these concerns were not confirmed through GPs experiences with the pilot. A number of specific information needs were identified by GPs to enable them to provide a supportive role to participants in the programme. CONCLUSION: The study has found considerable GP support for the introduction of the new Bowel Cancer Screening Programme. Nonetheless, GPs hold some significant reservations regarding the programme. It is important that the information needs of GPs and other members of the primary care team are addressed prior to the roll-out of the programme so they are equipped to promote informed choice and provide support to patients who consult them with queries regarding screening

Functional forms of socio-territorial inequities in breast cancer screening – A French cross-sectional study using hierarchical generalised additive models

To reduce the breast cancer burden, the French National Organised Breast Cancer Screening Programme (FNOBCSP) was implemented in 2004. The recommended participation rate has never been achieved and socio-territorial inequities in participation have been reported on several occasions. We investigated the functional forms and consistency of the relationships between neighbourhood deprivation, travel time to the nearest accredited radiology centre and screening uptake. We used two-level hierarchical generalised additive models in 8 types of territories classified by socio-demographic and economic factors. The first level was 368,201 women aged 50–72 invited to the 2013–2014 screening campaign in metropolitan France. They were nested in 41 départements, the level of organisation of the FNOBCSP. The effect of travel time showed two main patterns: it was either linear (with participation decreasing as travel time increased) or participation first increased with increasing travel time to a peak around 5–15 min and decreased afterward. In nearly all types and départements, the probability of participation decreased linearly with increasing deprivation. Territorial inequities in participation were more context-dependent and complex than social inequities. Inequities in participation represent a loss of opportunity for individuals who already have the worst cancer outcomes. Evidence-based public health policies are needed to increase the effectiveness and equity of breast cancer screening

Does community deprivation determine longevity after the age of 75? A cross-national analysis

Objectives: Analyze the association between socioeconomic deprivation and old-age survival in Europe, and investigate whether it varies by country and gender. Methods: Our study incorporated five countries (Portugal, Spain, France, Italy, and England). A 10-year survival rate expressing the proportion of population aged 75–84 years who reached 85–94 years old was calculated at area-level for 2001–11. To estimate associations, we used Bayesian spatial models and a transnational measure of deprivation. Attributable/prevention fractions were calculated. Results: Overall, there was a significant association between deprivation and survival in both genders. In England that association was stronger, following a dose–response relation. Although lesser in magnitude, significant associations were observed in Spain and Italy, whereas in France and Portugal these were even weaker. The elimination of socioeconomic differences between areas would increase survival by 7.1%, and even a small reduction in socioeconomic differences would lead to a 1.6% increase. Conclusions: Socioeconomic deprivation was associated with survival among older adults at ecological-level, although with varying magnitude across countries. Reasons for such cross-country differences should be sought. Our results emphasize the importance of reducing socioeconomic differences between areas.This work was supported by Portuguese funds through FCT—Fundação para a Ciência e a Tecnologia in the framework of project UID/BIM/04293/2013. AIR and MFP would also like to thank to FC—Fundação para a Ciência e a Tecnologia for the Grants PTDC/SAU-EPI/113424/2009 and SFRH/BD/82529/2011. MSC was supported by CNpQ (309692/2013-0) and FAPERJ (E-26/203.557/2014).We are very grateful to the National Statistic Offices for sending us the required data and to all the members of the European Deprivation Index (EDI) team. The authors would like to thank Rogério Ribeiro for the help in preparing visual supports, Alexandra Guttentag for her work as language editor, and the anonymous reviewers for their highly valuable corrections and suggestions

Circulating adrenomedullin estimates survival and reversibility of organ failure in sepsis: the prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock-1 (AdrenOSS-1) study

Background: Adrenomedullin (ADM) regulates vascular tone and endothelial permeability during sepsis. Levels of circulating biologically active ADM (bio-ADM) show an inverse relationship with blood pressure and a direct relationship with vasopressor requirement. In the present prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock 1 (, AdrenOSS-1) study, we assessed relationships between circulating bio-ADM during the initial intensive care unit (ICU) stay and short-term outcome in order to eventually design a biomarker-guided randomized controlled trial. Methods: AdrenOSS-1 was a prospective observational multinational study. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use, and need for renal replacement therapy. AdrenOSS-1 included 583 patients admitted to the ICU with sepsis or septic shock. Results: Circulating bio-ADM levels were measured upon admission and at day 2. Median bio-ADM concentration upon admission was 80.5 pg/ml [IQR 41.5-148.1 pg/ml]. Initial SOFA score was 7 [IQR 5-10], and 28-day mortality was 22%. We found marked associations between bio-ADM upon admission and 28-day mortality (unadjusted standardized HR 2.3 [CI 1.9-2.9]; adjusted HR 1.6 [CI 1.1-2.5]) and between bio-ADM levels and SOFA score (p < 0.0001). Need of vasopressor/inotrope, renal replacement therapy, and positive fluid balance were more prevalent in patients with a bio-ADM > 70 pg/ml upon admission than in those with bio-ADM ≤ 70 pg/ml. In patients with bio-ADM > 70 pg/ml upon admission, decrease in bio-ADM below 70 pg/ml at day 2 was associated with recovery of organ function at day 7 and better 28-day outcome (9.5% mortality). By contrast, persistently elevated bio-ADM at day 2 was associated with prolonged organ dysfunction and high 28-day mortality (38.1% mortality, HR 4.9, 95% CI 2.5-9.8). Conclusions: AdrenOSS-1 shows that early levels and rapid changes in bio-ADM estimate short-term outcome in sepsis and septic shock. These data are the backbone of the design of the biomarker-guided AdrenOSS-2 trial. Trial registration: ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015

Global surveillance of cancer survival 1995-2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2)

BACKGROUND: Worldwide data for cancer survival are scarce. We aimed to initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as a metric of the effectiveness of health systems, and to inform global policy on cancer control. METHODS: Individual tumour records were submitted by 279 population-based cancer registries in 67 countries for 25·7 million adults (age 15-99 years) and 75,000 children (age 0-14 years) diagnosed with cancer during 1995-2009 and followed up to Dec 31, 2009, or later. We looked at cancers of the stomach, colon, rectum, liver, lung, breast (women), cervix, ovary, and prostate in adults, and adult and childhood leukaemia. Standardised quality control procedures were applied; errors were corrected by the registry concerned. We estimated 5-year net survival, adjusted for background mortality in every country or region by age (single year), sex, and calendar year, and by race or ethnic origin in some countries. Estimates were age-standardised with the International Cancer Survival Standard weights. FINDINGS: 5-year survival from colon, rectal, and breast cancers has increased steadily in most developed countries. For patients diagnosed during 2005-09, survival for colon and rectal cancer reached 60% or more in 22 countries around the world; for breast cancer, 5-year survival rose to 85% or higher in 17 countries worldwide. Liver and lung cancer remain lethal in all nations: for both cancers, 5-year survival is below 20% everywhere in Europe, in the range 15-19% in North America, and as low as 7-9% in Mongolia and Thailand. Striking rises in 5-year survival from prostate cancer have occurred in many countries: survival rose by 10-20% between 1995-99 and 2005-09 in 22 countries in South America, Asia, and Europe, but survival still varies widely around the world, from less than 60% in Bulgaria and Thailand to 95% or more in Brazil, Puerto Rico, and the USA. For cervical cancer, national estimates of 5-year survival range from less than 50% to more than 70%; regional variations are much wider, and improvements between 1995-99 and 2005-09 have generally been slight. For women diagnosed with ovarian cancer in 2005-09, 5-year survival was 40% or higher only in Ecuador, the USA, and 17 countries in Asia and Europe. 5-year survival for stomach cancer in 2005-09 was high (54-58%) in Japan and South Korea, compared with less than 40% in other countries. By contrast, 5-year survival from adult leukaemia in Japan and South Korea (18-23%) is lower than in most other countries. 5-year survival from childhood acute lymphoblastic leukaemia is less than 60% in several countries, but as high as 90% in Canada and four European countries, which suggests major deficiencies in the management of a largely curable disease. INTERPRETATION: International comparison of survival trends reveals very wide differences that are likely to be attributable to differences in access to early diagnosis and optimum treatment. Continuous worldwide surveillance of cancer survival should become an indispensable source of information for cancer patients and researchers and a stimulus for politicians to improve health policy and health-care systems

Social and geographic disparities in access to reference care site for patients with colorectal cancer in France

The aim of this study was to investigate the relationship between social and geographic characteristics and the type of care centre for initial colorectal surgery in France. Patients living far from a reference cancer site were less frequently treated in a reference cancer site than those who were living near a reference cancer site ORa=(0.50 (0.33–0.76)). As for topography and emergency presentation, place of residence (urban/rural), occupation and marital status were not associated with the type of the care centre. Improvements in diagnosis and treatment and of clinical practice guidelines are therefore crucial to ensure equality in health care in France

TP53 mutations, amplification of P63 and expression of cell cycle proteins in squamous cell carcinoma of the oesophagus from a low incidence area in Western Europe

In Europe, high incidence rates of oesophageal squamous cell carcinoma (SCCE) are observed in western France (Normandy and Brittany) and in north-eastern Italy. Analysis of TP53 mutations in tumours from these regions has shown a high prevalence of mutations at A:T basepairs that may result from DNA damage caused by specific mutagens. However, the spectrum of TP53 mutations in regions of low incidence is unknown. We report here TP53 mutation analysis in 33 SCCE collected in Lyon, an area of low incidence. These tumours were also examined for MDM2 and P63 amplification, and for expression of p16INK4a/CDKN2a, cyclin E, p27Kipland Cox2. TP53 mutations were detected in 36% of the cases (12/33). In contrast with regions of high incidence, the mutation spectrum did not show a high prevalence of mutations at A:T base pairs. P63 was amplified in 5/32 cases tested (15.5%). No amplification of MDM2 was found. Expression studies revealed frequent loss of p16INK4a/CDKN2a(46%) and p27Kipl(25%) expression, and frequent overexpression of Cyclin E (70%) and Cox2 (42%). Overall, these results indicate that in Europe, SCCE from areas of high and low incidence present a similar pattern of molecular alterations but differ by the type of TP53 mutations. © 2001 Cancer Research Campaign http://www.bjcancer.co