Search

Background Urinary 8‐isoprostane is an established biomarker for lipid peroxidation. However, the association between its pre-diagnostic levels and cancer incidence has rarely been evaluated. Methods 8793 older adults from the German ESTHER cohort were followed up for cancer incidence by cancer registry data. A directed acyclic graph was utilized to identify potential confounders. Multivariate Cox regression models were applied to estimate hazard ratios (HRs) and 95% confidence intervals (95% CI). Results During 14-year follow-up, 1540 incident cancer cases, including 207 lung, 196 colorectal, 218 breast and 245 prostate cancer cases were detected. 8-isoprostane concentrations were positively associated with lung cancer, but not with cancer at the other sites. The HR (95% CI) for the association with lung cancer was 1.61 (1.10, 2.34) for comparison of the top with bottom tertile in total population. The association of 8-isoprostane levels with lung cancer persisted after the adjustment for smoking and other potential confounders and was multiplicative to the effect of smoking. However, 8-isoprostane levels did not improve lung cancer prediction when added to a model containing age, sex and smoking. A protective association of increasing 8-isoprostane levels was observed for prostate cancer incidence but this association was only statistically significant among current smokers. Discussion Our findings suggest that lipid peroxidation is involved in the development of lung cancer. However, high oxidative stress may be a protective factor for prostate cancer, especially among current smokers. [ABSTRACT FROM AUTHOR]

Background: Evidence of an inverse association between serum vitamin D and mortality from epidemiological studies has prompted efforts to reduce mortality by vitamin D supplementation, either in targeted interventions for people with vitamin D insufficiency or deficiency, or in untargeted interventions regardless of baseline vitamin D status.Objective: We aimed to assess the expected impact of the 2 different approaches on effect sizes and power of intervention studies.Methods: Serum concentrations of 25-hydroxyvitamin D [25(OH)D] were measured in 9579 participants aged 50-75 y in the German Epidemiologische Studie zu Chancen der Verhütung, Früherkennung und optimierten Therapie chronischer Erkrankungen in der älteren Bevölkerung (ESTHER) study who were followed for mortality for a median of 12.4 y. We estimated adjusted HRs of mortality from all causes, cardiovascular disease, and cancer for defined increases in serum 25(OH)D by Cox regression, both across the full range of 25(OH)D concentrations and for those with vitamin D insufficiency [30 nmol/L ≤ 25(OH)D < 50 nmol/L] or deficiency [25(OH)D <30 nmol/L] only, and we calculated the power of intervention studies achieving those effect sizes.Results: An inverse association between serum 25(OH)D and mortality was observed only for participants with vitamin D insufficiency or deficiency and was strongest for the latter. Accordingly, the expected effects were much stronger and the expected power was much higher for interventions that targeted these groups than for untargeted interventions. For example, a targeted intervention study with 10,000 older adults (age 50-75 y) with serum 25(OH)D <50 nmol/L that increases serum 25(OH)D concentrations by 20 nmol/L in the intervention group (n = 5000) would be expected to yield a 26% reduction of all-cause mortality that could be detected with 89% power within 5 y of follow-up compared with a 10% mortality reduction and 20% power in an untargeted intervention study of the same size.Conclusions: Vitamin D supplementation trials aimed at reducing mortality in older adults have much higher power when focused on those with low serum 25(OH)D concentrations. [ABSTRACT FROM AUTHOR]

Background: The proportion of cases notified by death certificate only (DCO) is a commonly used data quality indicator in studies comparing cancer survival across regions and over time. We aimed to assess dependence of DCO proportions on the age structure of cancer patients. Methods: Using data from a national cancer survival study in Germany, we determined age specific and overall (crude) DCO proportions for 24 common forms of cancer. We then derived overall (crude) DCO proportions expected in case of shifts of the age distribution of the cancer populations by 5 and 10 years, respectively, assuming age specific DCO proportions to remain constant. Results: Median DCO proportions across the 24 cancers were 2.4, 3.7, 5.5, 8.5 and 23.9% in age groups 15-44, 45-54, 55-64, 65-74, and 75+, respectively. A decrease of ages by 5 and 10 years resulted in decreases of cancer specific crude DCO proportions ranging from 0.4 to 4.8 and from 0.7 to 8.6 percent units, respectively. Conversely, an increase of ages by 5 and 10 years led to increases of cancer specific crude DCO proportions ranging from 0.8 to 4.8 and from 1.8 to 9.6 percent units, respectively. These changes were of similar magnitude (but in opposite direction) as changes in crude 5-year relative survival resulting from the same shifts in age distribution. Conclusions: The age structure of cancer patient populations has a substantial impact on DCO proportions. DCO proportions should therefore be age adjusted in comparative studies on cancer survival across regions and over time. [ABSTRACT FROM AUTHOR]

Aim Endoscopy based screening programmes for colorectal cancer (CRC) are being implemented in an increasing number of countries. In Germany, screening colonoscopy at age 55 or older has been offered since the end of 2002. We aimed to estimate the long-term impact of this offer on CRC prevention. Methods We estimated numbers of prevented CRC cases by expected age and year of their (prevented) occurrence over four decades (2005–2045) by four state Markov models (non-advanced adenoma, advanced adenoma, preclinical CRC, clinically manifest CRC). Estimates are based on screening colonoscopies reported to the German screening colonoscopy registry in 2003–2012 ( N = 4,407,971), transition rates between the four states and general population mortality rates. Results Numbers of prevented clinically manifest CRC cases are projected to increase from <100 in 2005 to approximately 6500 in 2015, 12,600 in 2025, 15,400 in 2035 and 16,000 in 2045, compared to approximately 58,000 incident cases observed in 2003. The annual number of prevented cases is expected to be higher among men than among women and to strongly vary by age. The vast majority of prevented cases would have occurred at age 75 or older. Conclusions Despite modest participation rates, the German screening colonoscopy programme will lead to substantial reductions in the CRC burden. The reductions will be fully disclosed in the long run only and predominantly affect numbers of incident cases above 75 years of age. Screening offers would need to start at younger ages in order to achieve more effective CRC prevention at younger ages. [ABSTRACT FROM AUTHOR]

Objectives: A common approach in the evaluation of screening for colorectal cancer (CRC) is comparing observed numbers of CRC deaths in screening participants with expected numbers derived from CRC mortality in the general population. We aimed to illustrate and quantify an often-overlooked bias that may occur in such studies if CRC mortality in the general population is not restricted by the date of diagnosis (whereas screening participants by definition do not have a prior CRC diagnosis). Study Design and Setting: We illustrate and quantify the expected bias using cancer registry data from the United States. Results: Unless an incidence-based mortality approach is used, expected numbers of CRC deaths in screening cohorts (and hence estimated screening effects) are substantially overestimated. Overestimation of expected CRC deaths is most severe (more than fivefold) during the first year of follow-up and rapidly decreases in the subsequent years. Nevertheless, overestimation of 5- and 10-year cumulative numbers of expected CRC deaths is still as high as 60-70% and 20-30%, respectively. Substantial bias even persists if the initial years of follow-up are excluded from the analyses. Conclusion: Careful restriction of expected CRC deaths by an incidence-based mortality approach is indispensable for deriving valid screening effect estimates. [ABSTRACT FROM AUTHOR]

Objectives: Although randomized controlled trials (RCTs) are considered the most valid approach to evaluate screening effects, they also face a number of methodological challenges, including nonadherence and contamination. We aimed to quantify their potential impact in RCTs evaluating endoscopic screening for colorectal cancer (CRC). Study Design and Setting: We carried out model calculations using plausible levels of nonadherence and contamination. Results: Assuming medium values of adherence (70%) and contamination, that is, use of lower gastrointestinal endoscopy other than the one offered for screening (30%), true reductions in CRC incidence or mortality of 70%, 50%, or 30% would be expected to be attenuated to reductions of 43%, 29%, and 16%, respectively, in intention-to-screen analyses. In case of low levels of adherence (50%) and high but realistic levels of contamination (50%), even more severe attenuation of screening effects to estimated reductions of 27%, 17%, and 9% would be expected. The estimates are only slightly modified in sensitivity analyses, additionally allowing for differential adherence and contamination according to CRC risk. Conclusion: In the era of widespread endoscopy use even outside the screening programs, RCTs may strongly underestimate the effects of CRC screening. Additional analyses accounting for nonadherence and contamination are crucial for disclosing the true screening effects. [ABSTRACT FROM AUTHOR]

Abstract: There is increasing evidence that faecal immunochemical tests (FITs) for haemoglobin offer a number of advantages over traditional guaiac based faecal occult blood tests (gFOBTs). However, evidence on diagnostic performance from direct comparisons with colonoscopy findings in all participants in the average risk population is still sparse. We aimed for a head-to-head comparison of three quantitative FITs with a gFOBT among participants of the German screening colonoscopy programme. Pre-colonoscopy stool samples and colonoscopy reports were obtained from 2235 participants of screening colonoscopy in 2005–2009. To enhance comparability of diagnostic performance of the various tests, we assessed sensitivity, specificity, predictive values and likelihood ratios of FITs after adjusting the FIT cut-off haemoglobin (Hb) concentrations in such a way that FIT positivity rates equalled the positivity rate of the gFOBT. Colorectal cancer, advanced adenomas and other adenomas were found in 15 (0.7%), 207 (9.3%) and 398 (17.8%) participants. The gFOBT was positive in 111 (5.0%) participants, with sensitivities (specificities) for detecting colorectal cancer, any advanced neoplasm or any neoplasm of 33.3% (95.2%), 8.6% (95.4%) and 5.5% (95.2%). At the same positivity rate, all three FITs outperformed the gFOBT in all indicators. In particular, all sensitivities of FITs were approximately two to three times higher at increased levels of specificity. All differences were statistically significant, except for some of the performance indicators for colorectal cancer. In conclusion, FITs can detect much larger proportions of colorectal neoplasms even if their cut-offs are set to levels that ensure equally low positivity rates as gFOBT. [Copyright &y& Elsevier]

Abstract: Period analysis is increasingly employed in analyses of long-term survival of patients with chronic diseases such as cancer, as it derives more up-to-date survival estimates than traditional cohort based approaches. It has recently been extended with regression modelling using generalized linear models, which increases the precision of the survival estimates and enables to assess and account for effects of additional covariates. This paper provides a detailed presentation how model based period analysis may be used to derive population-based absolute and relative survival estimates using the freely available R language and statistical environment and already available R programs for period analysis. After an introduction of the underlying regression model and a description of the software tools we provide a step-by-step implementation of two regression models in R and illustrate how estimates and a test for trend over time in relative survival may be derived using data from a population based cancer registry. [Copyright &y& Elsevier]

Abstract: Background : The proportion of cases notified by death certificate only (DCO) is a commonly used criterion to judge completeness of cancer registration even though it is affected by additional factors, particularly during initial years of newly established registries. Methods : Based on cancer registry data from the United States, we provide model calculations to demonstrate the magnitude and time course of the impact of the following mechanisms on DCO proportions of “young” registries: registration of cancer deaths from patients diagnosed prior to the registration period and delayed registration by death certificate of patients diagnosed but not reported after initiation of registration. Results : DCO proportions of up to ⩾30% can be expected from deaths of previously diagnosed patients during the first year of registration. Although this proportion is expected to gradually diminish over subsequent years, DCO proportions may be dominated for several years by this source, which may still be relevant after 10 or more years of cancer registration for cancers with relatively large proportions of late deaths. Otherwise, however, underreporting during patients’ lifetime is expected to become the predominant source of DCO proportions in the long run. Conclusions : Our results may guide interpretation of DCO proportions of relatively “young” cancer registries. [Copyright &y& Elsevier]

Objectives: In the evaluation of cancer screening tests, cancer-free controls are often matched to cancer cases on factors such as sex and age. We assessed the potential merits and pitfalls of such matching using an example from colorectal cancer (CRC) screening. Study Design and Setting: We compared sex and age distribution of CRC cases and cancer-free people undergoing screening colonoscopy in Germany in 2006 and 2007. We assessed specificity by sex and age of two immunochemical fecal occult blood tests (iFOBTs) in a study among screening colonoscopy participants conducted in the same years, and we assessed the expected impact of matching by sex and age on the validity of specificity estimates at various cut points. Results: In the screening colonoscopy program, the proportion of men and mean age were 59.6% and 68.6 years among 10,324 CRC patients compared with 45.6% and 64.7 years, respectively, among 997,490 cancer-free participants. The specificity of the iFOBTs was higher among women than among men and decreased with age. Matching of cancer-free controls by age and sex would have led to the underestimation of specificity at all cut points assessed. Conclusion: In the evaluation of cancer screening tests, matching of controls may lead to biased estimates of specificity. [ABSTRACT FROM AUTHOR]

Abstract: Background: Survival studies using data from population-based cancer registries allow assessing effectiveness of cancer care on a population level. However, population-based cancer registries differ in the proportion of cases first notified by death certificate, as well as in the efforts to trace back such death certificate notifications (DCN). We aimed to assess the impact of such trace back on population-based cancer survival estimates. Materials and methods: In this study from the population-based Saarland Cancer Registry (Germany) we investigated the survival experience of successfully traced back DCN cases from 1994 to 2003. Five-year relative survival of patients with DCN cancers and the effect of trace back on population-based 5-year relative survival estimates were analysed by age and tumour site. Results: Twelve percent of all cancers were DCN and such cases occurred most often amongst sites with poor prognosis and amongst elderly patients. Approximately half of DCN cases could be successfully traced back. Five-year relative survival of patients with DCN cancers with trace back was 2%. The inclusion of DCN cancers with additional registrations reduced the 5-year relative survival estimate for all cancers combined by 4% points. Reductions were stronger for older patients and highly fatal cancers. Conclusions: Trace back results in increased inclusion of patients with very poor prognosis. Varying extent of trace back across registries may compromise comparability of cancer survival estimates and should be taken into account in comparative cancer survival studies. [Copyright &y& Elsevier]

Abstract: Objective: Chronic kidney disease (CKD) increases risk of coronary heart disease (CHD), but the impact of using different equations for estimating kidney function on CHD is not clear yet. This study described the prognostic value of CKD as defined by various creatinine- (Cr-eGFR) and cystatin C-based estimating (Cys-eGFR) equations and their combinations on subsequent cardiovascular disease (CVD) events in patients with CHD. Design: Cohort study. Setting: Patients with coronary heart disease in in-patient rehabilitation and long-term follow-up (mean 63.4 months). Subjects: 1050 patients with coronary heart disease aged 30–70 years at baseline. Methods: CKD was defined as eGFR<60mL/min/1.73m2 (CKD stages 3–5) estimated by three Cr-eGFR equations (Cockroft–Gault equation adjusted for body surface area (CG/BSA), Modification of Diet in Renal Disease Study (MDRD) equation, CKD-EPIcrea) and by two Cys-eGFR equations (Arnal-Dade equation, CKD-EPIcys) and a combination. The primary endpoint of our study was subsequent CVD events. Results: During follow-up 118 patients (11.2%) experienced the outcome of our study. CKD assessed by the CG/BSA, MDRD, and CKD-EPIcrea equations showed no statistically significant association with subsequent CVD events after adjustment for multiple covariates (hazard ratio (HR) 1.45 [95% CI, 0.81–2.59], HR 1.47 [95% CI, 0.84–2.60], and HR 1.31 [95% CI, 0.72–2.83], respectively). By contrast, the Cys-eGFR equations were much stronger associated with subsequent CVD endpoints (Arnal-Dade: HR, 2.01 [95% CI, 1.34–3.04]; CKD-EPIcys HR, 2.22 [95% CI, 1.46–3.37]). The CKD-EPIcys also provided the highest area under the curve value. Conclusion: Our study shows that prevalent CKD is an independent risk factor for subsequent CVD in patients with prevalent CHD and implies that Cys-eGFR equations show a better clinical utility compared to the Cr-eGFR equations. [Copyright &y& Elsevier]

Abstract: Within the past 10–15 years, major advances in therapy have strongly improved prognosis of patients with chronic myelocytic leukaemia (CML). We estimated trends in 5- and 10-year relative survival of patients developing CML after a previous malignancy in the United States from 1990–1994 to 2000–2004. Period analysis was employed to disclose recent developments with minimum delay. Overall, 5- and 10-year relative survival increased from 17.6% to 37.7% (p <0.0001) and from 7.6% to 23.8% (p <0.0001), respectively. Improvements were particularly strong in younger age groups. Prognosis of CML patients with previous malignancy no longer lags behind prognosis of patients with primary CML. [Copyright &y& Elsevier]

Abstract: In late 2002, colonoscopy was introduced as a primary screening tool for colorectal cancer (CRC) in Germany. We aimed to estimate the expected reduction in case numbers and incidence of CRC between 2003 and 2010 by detection and removal of advanced adenomas. Data from 1,875,708 women and men included in the national screening colonoscopy database were combined with estimates of transition rates of advanced adenomas and with national population projections. Despite relatively low screening participation, incident CRC cases are expected to be reduced by more than 15,000 between 2003 and 2010. The impact is expected to be largest in age groups 55–59, 60–64 and 65–69 in whom total case numbers in 2010 are expected to be reduced by 13%, 19% and 14% among women, and by 11%, 15% and 12%, respectively, among men. Our results forecast a major rapid reduction of the CRC burden in Germany by screening colonoscopy. [Copyright &y& Elsevier]

Abstract: Period analysis has been shown to provide more up-to-date estimates of long-term cancer survival rates than traditional cohort-based analysis. Here, we provide detailed period estimates of 5- and 10-year relative survival by cancer site, country, sex and age for calendar years 2000–2002. In addition, pan-European estimates of 1-, 5- and 10-year relative survival are provided. Overall, survival estimates were mostly higher than previously available cohort estimates. For most cancer sites, survival in countries from Northern Europe, Central Europe and Southern Europe was substantially higher than in the United Kingdom and Ireland and in countries from Eastern Europe. Furthermore, relative survival was also better in female than in male patients and decreased with age for most cancer sites. [Copyright &y& Elsevier]

Abstract: Helicobacter pylori infection is a strong risk factor for gastric cancer. A positive association with colorectal cancer has also been suggested, but available evidence remains inconclusive. In this population-based case-control study we investigated the association between H. pylori seroprevalence and colorectal adenocarcinoma under consideration of pro-inflammatory gene polymorphisms (384 incident cancer patients, 467 matched control subjects). Overall, the H. pylori seroprevalence was higher among cases (51%) than among controls (44%), and a positive association between H. pylori seroprevalence and colorectal adenocarcinoma risk was found, that persisted after adjustment for known potential confounders, including measures of socioeconomic status (odds ratio (OR)=1.41; 95% confidence intervals (CI), 1.06–1.87). Presence of specific H. pylori cytotoxin-associated gene A (CagA) antibodies did not significantly affect the observed risk. Additionally, a pro-inflammatory genotype did not increase the colorectal cancer risk associated with H. pylori infection. H. pylori positive subjects carrying the pro-inflammatory genotypes even had a lower risk. [Copyright &y& Elsevier]

Abstract: In many cancer registries, registration of new cases is somewhat less up-to-date than mortality follow-up. In such situations, hybrid analysis, a combination of cohort and period analysis, rather than ‘pure’ period analysis has been proposed to derive up-to-date survival estimates. We evaluate application and adaptation of a modelling strategy that has recently been introduced to enhance precision of period survival estimates, to ‘hybrid type of data’. Using data from the Finnish Cancer Registry, we show that modelling again strongly increases precision of survival estimates. Furthermore, special models adapted to the hybrid type of data are shown to provide even more precise and, in a clear majority of cases, also more valid predictions of survival of recently diagnosed patients than models ignoring the hybrid type of data. Finally, we show that model-based estimation of and testing for recent trends may give different answers if period rather than hybrid modelling is used for hybrid type of registry data. We conclude that modelling is useful for both hybrid and period analyses of cancer survival, but the different data structure needs to be taken into account in the set-up of models. [Copyright &y& Elsevier]

Abstract: Objective: We investigated prospectively the role of cytomegalovirus (CMV) sero-status in the development of secondary cardiovascular disease (CVD) events in patients with coronary heart disease (CHD) under special consideration of diabetes mellitus. Background: There have been suggestions of an association between cytomegalovirus infection sero-status and development of secondary cardiovascular events. Patients with diabetes might be at higher risk since they are relatively immunocompromised. Methods: Patients aged 30–70 undergoing an in-patient rehabilitation program after acute manifestation of coronary heart disease between January 1999 and May 2000 were included in this analysis. CMV status at baseline was measured by serum immunoglobulin G antibodies. Secondary CVD events (myocardial infarction, stroke, and cardiovascular death) were recorded during a mean follow-up period of 33.5 months. Results: Among the 1033 subjects with measured IgG antibody for CMV, 56.5% were sero-positive to CMV at baseline. During follow-up, secondary CVD events occurred among 71 (6.9%) participants. Occurrence of a secondary CVD event was more common among sero-positive than among sero-negative patients (adjusted hazard ratio, HR, 1.31, 95% confidence interval (CI) 0.80–2.20), among patients with diabetes HR 2.00 (95% CI 1.20–3.25). The risk of secondary CVD events was strongly increased among patients with both a positive CMV sero-status and diabetes (adjusted HR 2.58, 95% CI 1.32–5.10) compared to CMV negative, non-diabetic patients, whereas either conditions alone was associated with a weak and non-significant increase in risk only. Conclusion: Our results are consistent with a possible moderate increase in risk of secondary CVD events among patients with a positive CMV sero-status, and they indicate a strongly increased risk among CMV positive patients with diabetes. [Copyright &y& Elsevier]

Purpose: Several mostly small-scale studies reported clustering of Helicobacter pylori infections as a possible indicator of conjugal transmission, but results have been inconsistent. We assessed clustering of H pylori infections in a large community-based study from Germany that included both high-prevalence and low-prevalence population subgroups. Methods: Current H pylori infection was determined among 670 couples by means of carbon-13-urea breath test (13C-UBT) breath test and a monoclonal antigen immunoassay for H pylori in stool. Results: Prevalences of infection among women were 34.9% (51 of 146 women) if the partner was infected and 14.5% (76 of 524 women) if the partner was not infected. Stratification by nationality showed a strong association of infection for partners with other than German nationality (adjusted odds ratio [OR], 6.05; 95% confidence interval [CI], 1.31–17.96), for whom prevalence of infection was greater than 50%, whereas no association was seen for German partners born in Germany (OR, 1.10; 95% CI, 0.47–2.61), for whom infection prevalence was approximately 10% (p for interaction = 0.048). Conclusions: Conjugal transmission of infection caused by H pylori is unlikely to be of relevance in low-prevalence population groups. Our results are consistent with the hypothesis of a potential role of conjugal transmission of H pylori infection in high-prevalence population groups. [Copyright &y& Elsevier]

Abstract: Background and Objective: Period analysis provides more up-to-date estimates of cancer patient survival than traditional methods, but there is a trade-off between up-to-dateness and precision. Our objective was to compare the performance of period and complete analysis in terms of up-to-dateness and precision of survival estimates. Study Design and Setting: Five-year relative survival data actually observed for patients diagnosed with 1 of 20 common forms of cancer in Finland in 36 overlapping 5-year periods between 1958–1962 and 1993–1997 were compared with period estimates and various variants of complete estimates of 5-year relative survival potentially available during these periods. Results: At comparable levels of up-to-dateness, survival estimates from period analysis were more precise than survival estimates from complete analysis. At comparable levels of precision, period analysis provided more up-to-date survival estimates than did complete analysis. Conclusion: These results further encourage more widespread use of period analysis as a standard tool for up-to-date monitoring of cancer patient survival by population-based cancer registries. [Copyright &y& Elsevier]

Abstract: Selective under-ascertainment of cancer patients by cancer registries may bias population-based estimates of cancer patient survival. As prognosis is strongly age related for many forms of cancer, age adjustment of cancer survival rates, which is primarily used to enhance the validity of comparative analyses between cancer populations, might also effectively reduce this type of bias. We empirically assessed this potential “side-effect” of age adjustment using data from the Finnish Cancer Registry. Analyses of five-year absolute and relative survival for patients diagnosed in 1990–1994, and age adjustment to the age structure of patients diagnosed in 1985–1989, were used as examples. Various patterns of selective under-ascertainment were simulated, and the bias in crude and age adjusted five-year survival rates was compared. Age adjusted estimates were less biased in most scenarios, which may be an additional argument for application of age adjustment in the analysis and reporting of population-based cancer survival rates. [Copyright &y& Elsevier]

Abstract: Up-to-date monitoring of long-term survival is an important task of population-based cancer registries. Period analysis, a new method of survival analysis introduced a few years ago, has been shown to be particularly useful for that purpose. The “classical” period analysis uses a life-table approach which requires both the year and month of diagnosis for implementation in pertinent software programs. However, an increasing number of cancer registries remove the month of diagnosis from their datasets, mainly to ensure the highest possible protection against re-identification of patients. In this paper, we present modifications of period analysis that allow the application of this technique, while almost completely preserving its advantages, in datasets without the month of diagnosis. The modified techniques are illustrated and evaluated using examples from the Surveillance, Epidemiology, and End Results (SEER) programme of the United States (US) National Cancer Institute (NCI), which also has removed month of diagnosis from its most recently released public use database. [Copyright &y& Elsevier]

Up-to-date monitoring of long-term survival is an important task of population-based and clinical cancer registries. A few years ago, a new method of survival analysis, denoted period analysis, was introduced to provide more up-to-date estimates of long-term survival. However, a prototypical period analysis may not be applicable in situations with delayed recording of incident cases. We introduce herein a hybrid type of analysis that combines elements of both traditional and period analyses which may still be feasible in such settings. The performance of the hybrid type of analysis compared with other design options is empirically evaluated and illustrated for children diagnosed with cancer in the United States. The empirical evaluation indicates that hybrid analysis may be useful to derive more up-to-date estimates of long-term survival compared with traditional design options if there is a strong improvement of survival over time, even in situations with a substantial delay in recording of incident cases. [Copyright &y& Elsevier]

Abstract: The measures of cancer prognosis most commonly reported by cancer registries are 5- or 10-year absolute or relative survival rates. Because cancer survival rates often vary by the age of cancer patients, and because the age structure of cancer patients often varies between populations, age adjustment is crucial for comparative analyses of cancer survival rates. However, traditional age adjustment often breaks down for long-term survival rates, particularly for sparse data, and it may provide inconsistent results for relative survival rates, even if age adjustment is made to the study population’s own age distribution. In this manuscript, we propose an alternative approach to age adjustment of both absolute and relative survival rates to overcome both the practical and conceptual problems inherent in traditional age adjustment. We outline the computational realisation of this approach, and we give an empirical illustration of its application using data from the nationwide Finnish Cancer Registry. [Copyright &y& Elsevier]

Epidemiology and Gerontology are relatively young scientific disciplines, both of which have had their own specific development in the past few decades. Only very recently, expertise from both fields has been brought together to extend and strengthen the spectrum of aging research. In this review, we outline the definition and methods of epidemiology and its historical development as a scientific discipline. We review and give examples of past and current contributions of epidemiology to aging research, and we outline the specific challenges, difficulties and opportunities encountered by epidemiologists in this field. We end up with an outlook on major challenges and opportunities for further development of epidemiology in aging research. We conclude that further integrative approaches with a particular emphasis on functional impairments are needed. Furthermore, the etiology of chronic diseases and impairments among the elderly cannot be studied by restricting the focus to health outcomes and their determinants at old age. Major efforts have to be made to incorporate measures of relevant determinants throughout the life span. Finally, epidemiologic methods should be more widely used for studies of medical and nursing care, and results of epidemiologic research need to be more effectively transferred into the practice of prevention. [Copyright &y& Elsevier]

In September 1995, the German Center for Research on Aging at the University of Heidelberg had been founded to become a leading national center of excellence with a clear interdisciplinary scope of ageing research activities. So far, three departments have been built up successively: the Department of Social and Environmental Gerontology (established in 1997, chair: Prof. Hans-Werner Wahl), the Department of Adult Development (established in 1998, provisional chair: Prof. Andreas Kruse), and the Department of Epidemiology (established in 2000, chair: Prof. Hermann Brenner). As one of the next steps, the disciplinary spectrum of the Center will be complemented by setting up several junior research groups in molecular ageing research. Within the few years of its existence, the Center has set up multiple large-scale, extramurally funded cross-sectional, case-control and longitudinal studies. These studies provide a unique common basis for interdisciplinary collaboration both within the Center and with the Center''s numerous national and international research partners. [Copyright &y& Elsevier]

Relative survival rates, such as 5- or 10-year relative survival rates, which quantify “net survival” of cancer patients, are the most commonly reported measures of cancer outcome by cancer registries. Because relative survival rates vary with age for many forms of cancer, and because the age distribution of cancer patients varies between different populations or within one population over time, age adjustment of relative survival rates is often employed in international comparisons or in time series analyses of cancer patient survival. In this article, we show that derivation of crude and of age-adjusted relative survival rates in the traditional way is conceptually inconsistent, and that this inconsistency has important practical implications. We show ways to overcome this inconsistency in the derivation and interpretation of crude and age-adjusted relative survival rates. [Copyright &y& Elsevier]

Aim: The purpose of the study was to assess the association between seropositivity to various infectious agents and stable coronary artery disease (CAD), controlling simultaneously for a variety of potential confounders. We also investigated whether the choice of a larger reference group might affect the results, and whether or not seropositivity to multiple agents was associated with a systemic inflammatory response. Methods: We assessed the simultaneous prevalence of antibodies against Helicobacter pylori, Chlamydia, cytomegalovirus, and herpes simplex virus in 312 patients with angiographically proven coronary artery disease (CAD) and in 479 age and sex matched controls. C-reactive protein, interleukin-6, fibrinogen, PAI-1-activity, d-dimer, von Willebrand Factor, plasma viscosity, and a complete blood cell count were determined in all subjects. Results: Seropositivity to all of the four agents was 21.8% in cases and 13.6% in controls (P=0.0003). We found a dose–response relationship between combined IgG-seropositivity to H. pylori, Chlamydia, cytomegalovirus, and herpes simplex virus and odds for the presence of angiographically confirmed stable CAD which, however, was strongly reduced after controlling for a variety of potential confounders. The dose–response pattern was no longer evident if a more stable reference group (subjects seropositive for two agents) was used instead of the relatively small reference group with zero or one seropositivity. We found no consistent pattern between IgG-seropositivity to several pathogens and inflammatory markers. Conclusions: Based on serological evidence of various infectious agents, this study suggests that the aggregate number of persistent infections is not independently associated with an increased risk for CAD if control for confounding and use of a stable reference group are guaranteed. [Copyright &y& Elsevier]

Helicobacter pylori colonizes the gastric mucosa. H. pylori infection is the main cause of peptic ulcer and gastric malignancy. This review gives an overview on the epidemiology of H. pylori infection and H. pylori-associated diseases in the developed world, mainly Europe, and it discusses very recent developments with regard to the prevalence and its future implications for H. pylori-associated diseases. [Copyright &y& Elsevier]

Objective: To analyze the relationship between social and familial factors, Helicobacter pylori infection and recurrent abdominal pain (RAP) in children in a population-based cross-sectional study among 1221 preschool children aged 5–8 years. Methods: H. pylori infection status was determined by 13C-urea breath test (13C-UBT) and information on medical history of the child and on RAP as well as on family demographics was obtained by a standardized questionnaire. Results: Overall, 129 children (11.3%) were infected with H. pylori and 29 children were identified as having RAP within the past 3 months (2.5%). Analysis by multiple logistic regression demonstrated a clear relationship of RAP with living in a single parent household [odds ratio (OR) 2.9, 95% confidence interval (95% CI) 1.2–6.7], with parental history of peptic ulcer (OR 3.7, 95% CI 1.3–10.4) and with parental history of nonulcer gastrointestinal disorders (OR 5.3, 95% CI 2.1–13.2). By contrast, there was a nonsignificant relation between H. pylori infection and occurrence of RAP (OR 1.6, 95% CI 0.5–5.5). Conclusion: Social and familial factors play a major role but not H. pylori infection in RAP. [Copyright &y& Elsevier]

• Frailty is rare (2.3 %) and polypharmacy common (18.3 %) in adults aged 40–69 years. • Frailty and polypharmacy are associated with cardiovascular disease and all-cause mortality, and major cardiovascular events. • Frailty and polypharmacy are independently associated with these outcomes. • The strongest association of polypharmacy with these outcomes is among (pre-)frail people. • Polypharmacy should be avoided in middle-aged adults, especially if they are (pre-)frail. Studies of the associations of polypharmacy and frailty with adverse health outcomes in middle-aged adults are limited. Furthermore, a potentially stronger association of polypharmacy with adverse health outcomes in frail than in non-frail adults is of interest. To evaluate associations of frailty (assessed using a frailty index) and polypharmacy (defined as taking five or more drugs) with major cardiovascular events, cancer incidence, all-cause, cardiovascular disease-specific, and cancer-specific mortality. Cox proportional hazards regression models were used to analyze 501,548 participants of the UK Biobank cohort study aged 40–69 years who were followed up for an average of 12 years. The prevalence of pre-frailty and frailty were 43.2 % and 2.3 %, respectively, and that of polypharmacy was 18.3 %. Although strongly associated with each other, frailty and polypharmacy were independently, statistically significantly associated with major cardiovascular events, cardiovascular disease-specific, and all-cause mortality. In addition, the hazard ratios of polypharmacy were stronger among (pre-)frail than non-frail study participants. No profound associations with cancer incidence and cancer mortality were observed. No sex and age differences were observed. This large cohort study showed that polypharmacy and frailty are independent risk factors for major cardiovascular events, cardiovascular disease-specific and all-cause mortality in both middle-aged (40–64 years) and older people (≥ 65 years). In addition, the hazard ratios of polypharmacy were stronger among (pre-)frail than non-frail study participants. This underlines the need to avoid polypharmacy as far as possible not only in older but also in middle-aged subjects (40–64 years), especially if they are pre-frail or frail. [ABSTRACT FROM AUTHOR]

Although the associations of serum 25-hydroxyvitamin D (25(OH)D) levels and vitamin D supplementation with total cancer mortality are well-known, evidence regarding the association of 25(OH)D and cancer site-specific mortality is predominantly limited to common cancer types, and most studies on vitamin D supplementation use have limitations on sample size and the adjustment of important confounding factors. We used cause-specific Cox regression models adjusted for 48 covariates to assess the associations of vitamin D deficiency, insufficiency, and vitamin D supplementation use with mortality from any cancer and 18 specific cancers in 411,436 United Kingdom Biobank participants, aged 40–69 years. The majority of the study population had either vitamin D deficiency (21.1%) or insufficiency (34.4%). Furthermore, 4.1% and 20.3% of the participants regularly took vitamin D or multivitamin supplements, respectively. During a median follow-up of 12.7 years, vitamin D deficiency was associated with significantly increased mortality from total cancer and four specific cancers: stomach (hazard ratio, 95% confidence interval: 1.42, 1.05–1.92), colorectal (1.27, 1.07–1.50), lung (1.24, 1.10–1.40), and prostate (1.36, 1.06–1.75). Vitamin D insufficiency was associated with increased colorectal (1.14, 1.00–1.30) and lung cancer mortality (1.19, 1.08–1.32). Compared to non-users, vitamin D use was associated with lower lung cancer (0.75, 0.60–0.95) and total cancer mortality. Multivitamin use was associated with lower mortality from melanoma (0.64, 0.43–0.97). Vitamin D deficiency and insufficiency were associated with increased mortality from multiple common cancers. The potential to reduce cancer mortality by vitamin D supplementation in populations with low 25(OH)D levels should be further explored. • Deaths due to 18 specific cancers were the outcomes of interest in the UK Biobank. • Vitamin D deficiency (VITD_D) and vitamin D supplements use (VITD_S) were assessed. • VITD_D was associated with lung, colorectal, prostate, and stomach cancer mortality. • VITD_S was significantly associated with a 25% lower lung cancer mortality. • Many lung cancer deaths may be preventable by VITD_S in people with VITD_D. [ABSTRACT FROM AUTHOR]

Survival for patients with acute myeloblastic leukemia (AML) has increased during the past two decades. However, socioeconomic disparities may affect survival for some patient populations. We examine survival by insurance type for patients with AML. Using data from the Surveillance, Epidemiology, and End Results database we estimated survival according to insurance status (no insurance, Medicaid, and other insurance) for patients diagnosed with AML in the United States in 2007–2013. One, 3-, and 5-year survival was lower for patients with no insurance and Medicaid than for patients with other insurance. Five-year survival estimates were 24.7%, 25.6%, and 35.7%, respectively, for patients with Medicaid, no insurance, and other insurance. After adjustment, hazard ratios of 1.46 for uninsured and 1.35 for Medicaid compared to other insurance for overall survival and 1.50 for uninsured and 1.30 for Medicaid compared to other insurance for AML-specific survival were observed. Similar results were seen in all ages and both genders. Patients with no insurance or Medicaid have lower survival expectations after diagnosis with AML than patients with other insurance. Further research into reasons for the poor outcomes for Medicaid patients and continued reduction of number of uninsured people are urgently needed to improve population-level outcomes for AML. [ABSTRACT FROM AUTHOR]

• Randomized trials have demonstrated considerable reduction in lung cancer mortality by screening heavy smokers with LDCT. • Selecting people at highest risk for screening to optimize the benefit/harm ratio is a major challenge and several LC risk models have been established for this. • Evaluation of eleven risk models and LDCT trial criteria in prospective cohort showed that LCRAT, LCDRAT and Bach models perform best in predicting lung cancer incidence and mortality. Randomized trials have demonstrated considerable reduction in lung cancer (LC) mortality by screening pre-selected heavy smokers with low-dose computed tomography (LDCT). Newer screening guidelines recommend refined LC risk models for selecting the target population for screening. We aimed to evaluate and compare the discrimination performance of LC risk models and previously used trial criteria in predicting LC incidence and mortality in a large German cohort of screening-age adults. Within ESTHER, a population-based prospective cohort study conducted in Saarland, Germany, 4812 ever smokers aged 50–75 years were followed up with respect to LC incidence and mortality for up to 17 years. We quantified the performance of 11 different LC risk models by the area under the curve (AUC) and compared the proportion of correctly predicted LC cases between the best performing models and the LDCT trial criteria. Risk prediction of LC incidence in the ESTHER ever smokers was best for the Bach model, LCRAT and LCDRAT with AUCs ranging from 0.782 to 0.787, from 0.770 to 0.774, and from 0.765 to 0.771 for the follow-up time periods of cases identified at 6, 11, and 17 years, respectively. At cutoffs yielding comparable positivity rates as the LDCT trial criteria, these models would have identified between 11.8 (95% CI 3.0–20.5) and 17.6 (95% CI 10.1–25.2) percent units higher proportions of LC cases occurring during the initial 6 years of follow-up. Use of LC risk models is expected to result in substantially greater potential to identify people at highest risk of LC, suggesting enhanced potential for reducing LC mortality by LC screening. [ABSTRACT FROM AUTHOR]

This systematic literature review aimed to investigate the extent to which transport-related interventions induced a reduction in car use. Both qualitative synthesis and meta -analysis were employed. The synthesis included 31 original studies, while the meta -analysis included 21. Of the qualitatively synthesised studies, 74 % demonstrated that interventions were effective in reducing car use. The pooled estimates of the effects showed a significant reduction in car usage with a mean effect size of Hedges' g = -0.117 (p = 0.024). The effect strongly varies across the studies due to considerable heterogeneity (I2 =.98, with a 95 % prediction interval from −0.589 to 0.355). At the moderator level, no significant differences were identified in the mean effect sizes for any subgroups, and the key factors could not be distinguished. The current body of evidence highlights that transport-related interventions can significantly influence car usage reduction, while literature suggests that this may benefit environment and society. [ABSTRACT FROM AUTHOR]

To evaluate the association of urinary oxidized guanine/guanosine (OxGuo) levels with incident type 2 diabetes (T2D) among older adults. A nested case-control design was applied with 440 cases of incident T2D and 440 controls, randomly sampled from all 65-75 year-old study participants of the ESTHER study, which is a population-based German cohort study with 14 years of follow-up. Analyses of 8-hydroxy-2′-deoxyguanosine (8-oxo-dGuo; DNA oxidation product) and 8-hydroxyguanosine (8-oxo-Guo; RNA oxidation product) were measured by ultra-performance liquid chromatography tandem-mass spectrometry (UPLC-MS/MS). The sum of the two OxGuo molecule concentrations was calculated and called OxGuo-UPLC-MS/MS. The corresponding OxGuo-ELISA levels were measured by Cayman's DNA/RNA oxidative damage ELISA, which detects a mix of 8-oxo-dGuo, 8-oxo-Guo and one other OxGuo molecule. Logistic regression was applied and models were adjusted for age, sex, BMI, HbA 1c , and C-reactive protein levels. 8-oxo-dGuo and 8-oxo-Guo were highly correlated with each other (r = 0.642) and weakly correlated with OxGuo-ELISA (r = 0.22 and r = 0.14, respectively). OxGuo-ELISA levels were statistically significant associated with T2D incidence (odds ratio (OR) and 95% confidence interval [95%CI] for comparison of top and bottom quartile: 1.77 [1.14; 2.76]). In contrast, the ORs did not increase stepwise from quartile 2 to 4 for neither 8-oxo-Guo, 8-oxo-dGuo levels nor OxGuo-UPLC-MS/MS and comparisons of top and bottom quartile were not statistically significant. In a post-hoc analysis comparing bottom quartile 1 with a combined group of quartile 2–4, the association of OxGuo-UPLC-MS/MS with T2D incidence reached statistical significance (OR [95%CI]: 0.66 [0.46; 0.96]) and was very similar with the one obtained for OxGuo-ELISA (OR [95%CI]: 0.66 [0.45; 0.95]). Although only the measurements of the DNA/RNA oxidative damage ELISA kit of Cayman were statistically significantly associated with T2D incidence in the main analysis, confidence intervals overlapped and the post-hoc analysis showed that results for OxGuo-UPLC-MS/MS were quite comparable. [Display omitted] • Oxidized guanine/guanosine molecules from DNA/RNA measured with ELISA + UPLC-MS/MS. • ELISA and UPLC-MS/MS based measurements in urine samples were weakly correlated. • 8-oxo-dGuo (DNA oxidation) and 8-oxo-Guo (RNA oxidation) were highly correlated. • 8-oxo-dGuo and 8-oxo-Guo contributed to the association of their sum with diabetes. • Comparable associations of ELISA and UPLC-MS/MS based measurements with diabetes. [ABSTRACT FROM AUTHOR]

• Federated learning with homomorphic encryption enables multiple parties to securely co-train artificial intelligence models in pathology and radiology, reaching state-of-theart performance with privacy guarantees. Artificial intelligence (AI) has a multitude of applications in cancer research and oncology. However, the training of AI systems is impeded by the limited availability of large datasets due to data protection requirements and other regulatory obstacles. Federated and swarm learning represent possible solutions to this problem by collaboratively training AI models while avoiding data transfer. However, in these decentralized methods, weight updates are still transferred to the aggregation server for merging the models. This leaves the possibility for a breach of data privacy, for example by model inversion or membership inference attacks by untrusted servers. Somewhat-homomorphically-encrypted federated learning (SHEFL) is a solution to this problem because only encrypted weights are transferred, and model updates are performed in the encrypted space. Here, we demonstrate the first successful implementation of SHEFL in a range of clinically relevant tasks in cancer image analysis on multicentric datasets in radiology and histopathology. We show that SHEFL enables the training of AI models which outperform locally trained models and perform on par with models which are centrally trained. In the future, SHEFL can enable multiple institutions to co-train AI models without forsaking data governance and without ever transmitting any decryptable data to untrusted servers. [ABSTRACT FROM AUTHOR]

Excess body weight and physical inactivity are key cancer risk factors contributing substantially to the cancer burden in Germany. We aimed to estimate the numbers and proportions of future cancer cases prevented under different scenarios of reducing the prevalence of excess body weight and physical inactivity in Germany. Based on a macro-simulation approach calculating age-, sex-, and cancer-site specific potential impact fractions, we estimated for a 30-year study period (2020–2050) numbers and proportions of cancer cases prevented under different scenarios of reducing excess body weight (overweight and obesity) and increasing levels of physical activity in the German population. Estimates of the prevented cancer burden varied in the different scenarios. In the guideline exposure scenarios, in which the prevalence of excess body weight and insufficient levels of physical activity would be eliminated, 8.7% (men: 10.1%; women: 7.8%) of overweight/obesity-related cancer cases and 2.4% (men: 2.3%; women: 2.4%) of cancer cases related to physical inactivity were estimated to be prevented over a 30-year period. This translates to approximately 662,000 (men: 304,000; women: 358,000) and 129,000 (men: 42,000; women: 87,000) prevented cancer cases, respectively. Our results illustrate that a substantial number of future cancer cases could be prevented in the German population by reducing excess body weight and physical inactivity. • Excess body weight and physical inactivity are key cancer risk factors in Germany. • Reducing these risk factors would prevent substantial numbers of future cancer cases. • Effective policy action is required to realise this potential for cancer prevention. [ABSTRACT FROM AUTHOR]

Lymph node status is a prognostic marker and strongly influences therapeutic decisions in colorectal cancer (CRC). The objective of the study is to investigate whether image features extracted by a deep learning model from routine histological slides and/or clinical data can be used to predict CRC lymph node metastasis (LNM). Using histological whole slide images (WSIs) of primary tumours of 2431 patients in the DACHS cohort, we trained a convolutional neural network to predict LNM. In parallel, we used clinical data derived from the same cases in logistic regression analyses. Subsequently, the slide-based artificial intelligence predictor (SBAIP) score was included in the regression. WSIs and data from 582 patients of the TCGA cohort were used as the external test set. On the internal test set, the SBAIP achieved an area under receiver operating characteristic (AUROC) of 71.0%, the clinical classifier achieved an AUROC of 67.0% and a combination of the two classifiers yielded an improvement to 74.1%. Whereas the clinical classifier's performance remained stable on the TCGA set, performance of the SBAIP dropped to an AUROC of 61.2%. Performance of the clinical classifier depended strongly on the T stage. Deep learning–based image analysis may help predict LNM of patients with CRC using routine histological slides. Combination with clinical data such as T stage might be useful. Strategies to increase performance of the SBAIP on external images should be investigated. • We aimed to develop a new biomarker to predict lymph node status of patients with colorectal cancer (CRC). • Convolutional neural network–based image analysis and clinical data were used individually and in combination. • Models were trained and tested on haematoxylin and eosin slides of 3013 primary CRC tumours. • The combined model on the internal test set yielded the best results (area under receiver operating curve of 74.1%). • Studies should address generalisation of the image classifier to external data. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To provide a systematic review of the relationship between age and leukocyte telomere length (LTL) in adults. Methods: Relevant studies were identified by a systematic search of Medline, EMBASE and ISI Web of Knowledge databases. Key data, such as age and LTL, were extracted from the studies along with correlation coefficients and yearly attrition rates where available. Obtained data were used to calculate weighted means and correlation coefficients. Results: Overall, 124 cross-sectional studies and 5 longitudinal studies were identified. A statistically significant inverse correlation between mean age and mean LTL across cross-sectional studies was observed for both absolute (r =−0.338, p <0.0001) and relative LTL (r =−0.295, p =0.0088). From mean LTL and ages, a yearly telomere loss of 24.7 base pairs (BP)/year was estimated by weighted linear regression. Weighted means of within study correlation of age and TL and yearly telomere loss rate estimates from cross-sectional studies were also in a similar order of magnitude (−0.380 and 21.91BP/year). The few longitudinal studies reported somewhat higher mean telomere loss rates (between 32.2 and 45.5BP/year). Conclusion: While a decrease of LTL with age is out of question, data on variation of the decrease according to sex, age and other potential determinants especially from longitudinal data are still sparse. [Copyright &y& Elsevier]

Summary: Background: Population-based cancer survival data, a key indicator for monitoring progress against cancer, are not widely available from countries in Africa, Asia, and Central America. The aim of this study is to describe and discuss cancer survival in these regions. Methods: Survival analysis was done for 341 658 patients diagnosed with various cancers from 1990 to 2001 and followed up to 2003, from 25 population-based cancer registries in 12 countries in sub-Saharan Africa (The Gambia, Uganda), Central America (Costa Rica), and Asia (China, India, Pakistan, Philippines, Saudi Arabia, Singapore, South Korea, Thailand, Turkey). 5-year age-standardised relative survival (ASRS) and observed survival by clinical extent of disease were determined. Findings: For cancers in which prognosis depends on stage at diagnosis, survival was highest in China, South Korea, Singapore, and Turkey and lowest in Uganda and The Gambia. 5-year ASRS ranged from 76–82% for breast cancer, 63–79% for cervical cancer, 71–78% for bladder cancer, and 44–60% for large-bowel cancers in China, Singapore, South Korea, and Turkey. Survival did not exceed 22% for any cancer site in The Gambia; in Uganda, survival did not exceed 13% for any cancer site except breast (46%). Variations in survival correlated with early detection initiatives and level of development of health services. Interpretation: The wide variation in cancer survival between regions emphasises the need for urgent investments in improving awareness, population-based cancer registration, early detection programmes, health-services infrastructure, and human resources. Funding: Association for International Cancer Research (AICR; St Andrews, UK), Association pour la Recherche sur le Cancer (ARC, Villejuif, France), and the Bill & Melinda Gates Foundation (Seattle, USA). [Copyright &y& Elsevier]

Summary: Background: Traditional cancer-survival analyses provide data on cancer management at the beginning of a study period, and are often not relevant to current practice because they refer to survival of patients treated with older regimens that might no longer be used. Therefore, shortening the delay in providing survival estimates is desirable. Period analysis can estimate cancer survival by the use of recent data. We aimed to apply the period-analysis method to data that were collected by European cancer registries to estimate recent survival by country and cancer site, and to assess survival changes in Europe. We also compared our findings with data on cancer survival in the USA from the US SEER (Surveillance, Epidemiology, and End Results) programme. Methods: We analysed survival data for patients diagnosed with cancer in 2000–02, collected from 47 of the European cancer registries participating in the EUROCARE-4 study. 5-year period relative survival for patients diagnosed in 2000–02 was estimated as the product of interval-specific relative survival values of cohorts with different lengths of follow-up. 5-year survival profiles for patients diagnosed in 2000–02 were estimated for the European mean and for five European regions, and findings were compared with US SEER registry data for patients diagnosed in 2000–02. A 5-year survival profile for patients diagnosed in 1991–2002 and a 10-year survival profile for patients diagnosed in 1997–2002 were also estimated by the period method for all malignancies, by geographical area, and by cancer site. Findings: For all cancers, age-adjusted 5-year period survival improved for patients diagnosed in 2000–02, especially for patients with colorectal, breast, prostate, and thyroid cancer, Hodgkin''s disease, and non-Hodgkin lymphoma. The European mean age-adjusted 5-year survival calculated by the period method for 2000–02 was high for testicular cancer (97·3% [95% CI 96·4–98·2]), melanoma (86·1% [84·3–88·0]), thyroid cancer (83·2% [80·9–85·6]), Hodgkin''s disease (81·4% [78·9–84·1]), female breast cancer (79·0% [78·1–80·0]), corpus uteri (78·0% [76·2–79·9]), and prostate cancer (77·5% [76·5–78·6]); and low for stomach cancer (24·9% [23·7–26·2]), chronic myeloid leukaemia (32·2% [29·0–35·7]), acute myeloid leukaemia (14·8% [13·4–16·4]), and lung cancer (10·9% [10·5–11·4]). Survival for patients diagnosed in 2000–02 was generally highest for those in northern European countries and lowest for those in eastern European countries, although, patients in eastern European had the highest improvement in survival for major cancer sites during 1991–2002 (colorectal cancer from 30·3% [28·3–32·5] to 44·7% [42·8–46·7]; breast cancer from 60% [57·2–63·0] to 73·9% [71·7–76·2]; for prostate cancer from 39·5% [35·0–44·6] to 68·0% [64·2–72·1]). For all solid tumours, with the exception of stomach, testicular, and soft-tissue cancers, survival for patients diagnosed in 2000–02 was higher in the US SEER registries than for the European mean. For haematological malignancies, data from US SEER registries and the European mean were comparable in 2000–02, except for non-Hodgkin lymphoma. Interpretation: Cancer-service infrastructure, prevention and screening programmes, access to diagnostic and treatment facilities, tumour-site-specific protocols, multidisciplinary management, application of evidence-based clinical guidelines, and recruitment to clinical trials probably account for most of the differences that we noted in outcomes. [Copyright &y& Elsevier]

Abstract: The Cys148Arg and Trp149Stop variants in the tumour suppressor gene ARLTS1 predispose to familial breast cancer, suggesting that these variants might also contribute to colorectal carcinogenesis. As the first to evaluate the association between Cys148Arg and Trp149Stop and colorectal cancer (CRC) risk, we genotyped 611 cases with CRC (including 77 cases with a first-degree family history) and 539 controls recruited from the German DACHS study. No significant differences in the genotype frequencies of Cys148Arg and Trp149Stop were observed between cases and controls. However, we showed a non-significant increased risk of familial CRC for both variants (OR=1.40 and 1.45), indicating a possible role of ARLTS1 in familial CRC. [Copyright &y& Elsevier]

Purpose: Several studies have demonstrated an inverse relationship between current moderate alcohol consumption and Helicobacter pylori (H. pylori) infection suggesting that alcohol consumption may facilitate elimination of this chronic infection. The aim of this study was to further explore this hypothesis by taking lifetime alcohol consumption, which may be a better marker of the relevant exposure than current alcohol consumption, into account. Methods: A total of 1206 patients between 30 and 70 years of age who underwent in-patient rehabilitation due to coronary heart disease were included in a cross sectional study carried out between January 1999 and April 2000. Participants provided information on average amount of alcohol consumed during past 12 months as well as during lifetime. H. pylori infection status was measured by serum immunoglobulin G antibodies. Results: There was an inverse non-linear relation between amount of current alcohol consumption and H. pylori seroprevalence. By contrast, we found an inverse dose–response relationship between lifetime alcohol consumption and H. pylori seroprevalence with the strongest risk reduction among subjects who had consumed more than 500,000 g of alcohol during life (adjusted odds ratio, 0.65; 95% confidence interval, 0.42–1.00). Conclusion: Our analysis supports the hypothesis that alcohol consumption may facilitate elimination of H. pylori infection among adults. [Copyright &y& Elsevier]

Gastrointestinal cancers account for approximately 20% of all cancer diagnoses and are responsible for 22.5% of cancer deaths worldwide. Artificial intelligence–based diagnostic support systems, in particular convolutional neural network (CNN)–based image analysis tools, have shown great potential in medical computer vision. In this systematic review, we summarise recent studies reporting CNN-based approaches for digital biomarkers for characterization and prognostication of gastrointestinal cancer pathology. Pubmed and Medline were screened for peer-reviewed papers dealing with CNN-based gastrointestinal cancer analyses from histological slides, published between 2015 and 2020.Seven hundred and ninety titles and abstracts were screened, and 58 full-text articles were assessed for eligibility. Sixteen publications fulfilled our inclusion criteria dealing with tumor or precursor lesion characterization or prognostic and predictive biomarkers: 14 studies on colorectal or rectal cancer, three studies on gastric cancer and none on esophageal cancer. These studies were categorised according to their end-points: polyp characterization, tumor characterization and patient outcome. Regarding the translation into clinical practice, we identified several studies demonstrating generalization of the classifier with external tests and comparisons with pathologists, but none presenting clinical implementation. Results of recent studies on CNN-based image analysis in gastrointestinal cancer pathology are promising, but studies were conducted in observational and retrospective settings. Large-scale trials are needed to assess performance and predict clinical usefulness. Furthermore, large-scale trials are required for approval of CNN-based prediction models as medical devices. • Computational medical image analysis is rising in gastrointestinal cancer pathology. • Several studies deal with CNN–based identification of biomarkers on HE slides. • Results are promising but studies are at early stages. • Further studies are needed to assess performance and potential clinical usefulness. [ABSTRACT FROM AUTHOR]

• Sex, smoking status and race interact with the BMI-survival relationship in Non-Small-Cell-Lung-Cancer patients in various ways. • Black patients had more favourable outcomes in the BMI-extremes when compared to White patients. • Female ever-smokers had worse outcomes when compared to male ever-smokers. • Asian patients and never smokers were not significantly associated with OS in general. • These distinct associations reflect sex and racial differences in body composition and etiological differences in NSCLC carcinogenesis. The relationship between Body-Mass-Index (BMI) and lung cancer prognosis is heterogeneous. We evaluated the impact of sex, smoking and race on the relationship between BMI and overall survival (OS) in non-small-cell-lung-cancer (NSCLC). Data from 16 individual ILCCO studies were pooled to assess interactions between BMI and the following factors on OS: self-reported race, smoking status and sex, using Cox models (adjusted hazard ratios; aHR) with interaction terms and adjusted penalized smoothing spline plots in stratified analyses. Among 20,937 NSCLC patients with BMI values, females = 47 %; never-smokers = 14 %; White-patients = 76 %. BMI showed differential survival according to race whereby compared to normal-BMI patients, being underweight was associated with poor survival among white patients (OS, aHR = 1.66) but not among black patients (aHR = 1.06; p interaction = 0.02). Comparing overweight/obese to normal weight patients, Black NSCLC patients who were overweight/obese also had relatively better OS (p interaction = 0.06) when compared to White-patients. BMI was least associated with survival in Asian-patients and never-smokers. The outcomes of female ever-smokers at the extremes of BMI were associated with worse outcomes in both the underweight (p interaction <0.001) and obese categories (p interaction = 0.004) relative to the normal-BMI category, when compared to male ever-smokers. Underweight and obese female ever-smokers were associated with worse outcomes in White-patients. These BMI associations were not observed in Asian-patients and never-smokers. Black-patients had more favorable outcomes in the extremes of BMI when compared to White-patients. Body composition in Black-patients, and NSCLC subtypes more commonly seen in Asian-patients and never-smokers, may account for differences in these BMI-OS relationships. [ABSTRACT FROM AUTHOR]

The research aimed to identify previously published CpG-methylation-based prognostic biomarkers and prediction models for colorectal cancer (CRC) prognosis and validate them in a large external cohort. A systematic search was conducted, analyzing 298 unique CpGs and 12 CpG-based prognostic models from 28 studies. After adjustment for clinical variables, 48 CpGs and five prognostic models were confirmed to be associated with survival. However, the discrimination ability of the models was insufficient, with area under the receiver operating characteristic curves ranging from 0.53 to 0.62. Calibration accuracy was mostly poor, and no significant added prognostic value beyond traditional clinical variables was observed. All prognostic models were rated at high risk of bias. While a fraction of CpGs showed potential clinical utility and generalizability, the CpG-based prognostic models performed poorly and lacked clinical relevance. [Display omitted] • A systematic review retrieved 298 CpG-methylation biomarkers and 12 CpG-based prediction models for colorectal cancer (CRC) prognosis. • Our external validation confirmed the prognostic value of 48 CpG-biomarkers and 5 prediction models. • Our analysis finds inadequate external model performance and a high risk of bias of published CpG-based prognostic models. [ABSTRACT FROM AUTHOR]

Tobacco smoking is the major preventable cause of cancer. Despite the longstanding decline in smoking prevalence, lung cancer remains one of the most frequently diagnosed cancers in both sexes. We aimed to estimate the current cancer burden attributable to smoking in Europe. Smoking-related cancer incidence by country, cancer type, sex and age in Europe was estimated from GLOBOCAN 2018. We applied a modified version of the indirect method to estimate the population attributable fraction (PAF) for lung cancer and applied Levin's formula to estimate the PAF for other smoking-related cancer sites. In Europe in 2018, 572,000 and 186,000 cancer cases were attributable to tobacco smoking in males and females respectively, accounting for 28% (males) and 10% (females) of all cancer cases. By region, the largest and the lowest PAF due to smoking in males occurred in Eastern Europe (35% of all cancer cases) and Northern Europe (21%), respectively. Among women, this pattern was reversed (16% in Northern Europe and 6% in Eastern Europe). Lung cancer accounted for more than half of the total cancer burden attributable to smoking (382,000). Other major contributors to the total PAF were lip, oral cavity and pharynx, bladder and laryngeal cancers in men (27% out of total PAF) and colorectal, pancreatic, oral cavity and pharyngeal cancers (21%) in women. Tobacco smoking was responsible for one in five cancer cases in Europe in 2018. The introduction and robust implementation of tobacco control programmes are critical to reduce this cancer burden in the future. • Despite health policy efforts smoking caused 1 in 5 cancer cases in Europe in 2018. • Regional variation in the range of 10–30% of cancer cases attributable to smoking. • The results suggest urgent need for tobacco control policies in the EU legislation. [ABSTRACT FROM AUTHOR]