Colorectal Cancer Screening: Tests, Strategies, and Perspectives

Screening has a central role in colorectal cancer (CRC) control. Different screening tests are effective in reducing CRC-specific mortality. Influence on cancer incidence depends on test sensitivity for pre-malignant lesions, ranging from almost no influence for guaiac-based fecal occult blood testing (gFOBT) to an estimated reduction of 66–90% for colonoscopy. Screening tests detect lesions indirectly in the stool [gFOBT, fecal immunochemical testing (FIT), and fecal DNA] or directly by colonic inspection [flexible sigmoidoscopy, colonoscopy, CT colonography (CTC), and capsule endoscopy]. CRC screening is cost-effective compared to no screening but no screening strategy is clearly better than the others. Stool tests are the most widely used in worldwide screening interventions. FIT will soon replace gFOBT. The use of colonoscopy as a screening test is increasing and this strategy has superseded all alternatives in the US and Germany. Despite its undisputed importance, CRC screening is under-used and participation rarely reaches 70% of target population. Strategies to increase participation include ensuring recommendation by physicians, introducing organized screening and developing new, more acceptable tests. Available evidence for DNA fecal testing, CTC, and capsule endoscopy is reviewed

Cytotoxic synergism of Clostridioides difficile toxin B with proinflammatory cytokines in subjects with inflammatory bowel diseases

Clostridioides difficile (C. difficile) is progressively colonizing humans and animals living with humans. During this process, hypervirulent strains and mutated toxin A and B of C. difficile (TcdA and TcdB) are originating and developing. While in healthy subjects colonization by C. difficile becomes a risk after the use of antibiotics that alter the microbiome, other categories of people are more susceptible to infection and at risk of relapse, such as those with inflammatory bowel disease (IBD). Recent in vitro studies suggest that this increased susceptibility could be due to the strong cytotoxic synergism between TcdB and proinflammatory cytokines the tumor necrosis factor-alpha and interferon-gamma (CKs). Therefore, in subjects with IBD the presence of an inflammatory state in the colon could be the driver that increases the susceptibility to C. difficile infection and its progression and relapses. TcdB is internalized in the cell via three receptors: chondroitin sulphate proteoglycan 4; poliovirus receptor-like 3; and Wnt receptor frizzled family. Chondroitin sulphate proteoglycan 4 and Wnt receptor frizzled family are involved in cell death by apoptosis or necrosis depending on the concentration of TcdB and cell types, while poliovirus receptor-like 3 induces only necrosis. It is possible that cytokines could also induce a greater expression of receptors for TcdB that are more involved in necrosis than in apoptosis. Therefore, in subjects with IBD there are the conditions: (1) For greater susceptibility to C. difficile infection, such as the inflammatory state, and abnormalities of the microbiome and of the immune system; (2) for the enhancement of the cytotoxic activity of TcdB +Cks; and (3) for a greater expression of TcdB receptors stimulated by cytokines that induce cell death by necrosis rather than apoptosis. The only therapeutic approach currently possible in IBD patients is monitoring of C. difficile colonization for interventions aimed at reducing tumor necrosis factor-alpha and interferon-gamma levels when the infection begins. The future perspective is to generate bacteriophages against C. difficile for targeted therapy

Estimates of the incidence of infection-related cancers in Italy and Italian regions in 2018

Introduction. Chronic infections and infestations represent one of the leading causes of cancer. Eleven agents have been categorized by the International Agency for Research on Cancer (IARC) in Group 1, 3 in Group 2A and 4 in Group 2B. We previously estimated that the incidence of cancers associated with infectious agents accounted for the 8.5% of new cancer cases diagnosed in Italy in 2014. Methods. In the present study we evaluated the incidence of cancer in Italy and in the 20 Italian regions in 2018, based on the data of Cancer Registries, and calculated the fraction attributable to infectious agents. Results. Cancers of infectious origin contributed to the overall burden of cancer in Italy with more than 27,000 yearly cases, the 92% of which was attributable to Helicobacter pylori, human papillomaviruses, and hepatitis B and C viruses. With the exception of papillomavirus-related cancers, the incidence of cancers of infectious origin was higher in males (16,000 cases) than in females (11,000 cases). There were regional and geographical variations of cancers depending on the type of cancer and on the gender. Nevertheless, the overall figures were rather similar, the infection-related cancers accounting for the 7.2, 7.6, and 7.1% of all cancers in Northern, Central, and Southern Italy, respectively. Conclusions. The estimate of the incidence of cancers attributable to infectious agents in Italy in 2018 (7.3% of all cancer cases) is approximately half of the worldwide burden, which has been estimated by IARC to be the 15.4% of all cancer cases in 2012

Regional indices of socio-economic and health inequalities: a tool for public health programming

Abstract OBJECTIVES. The aim was to provide an affordable method for computing socio-economic deprivation indices at regional level, to reveal the specific aspects of the relationship between socio-economic (SE) inequalities and health outcomes. The Umbria region Socio-Health Index (USHI) was computed and compared to the Italian National Deprivation Index at Umbria region level (NDI-U).METHODS. The USHI was computed by applying factor analysis to census tract SE variables correlated to the general mortality and validated in comparison with the NDI-U.RESULTS. Overall mortality presented linear positive USHI trends, while trends for NDI-U resulted non-linear or not-significant. Similar and relevant results were obtained for specific causes of death by deprivation groups, gender and age.CONCLUSIONS. The USHI better describes a local population by SE health-related status. Therefore, policy makers could adopt this method to obtain a better picture of SE-associated health conditions in regional population and target strategies for reducing inequalities in health

Design and validation of a self-administered questionnaire to assess knowledge, attitudes and behaviours about Zika virus infection among general population in Italy

  Background Zika (ZIKV), a flavivirus firstly identified in rhesus monkeys in Zika Forest of Uganda, in 1947, is an emerging virus  transmitted mainly by mosquitoes bites. Due to ZIKV adaptation to humans, that can maintain a mosquito-human-mosquito transmission cycle, it is essential to know the attitudes, knowledge and behaviours of general population regarding ZIKV prevention. Our main study aims were to develop and validate a questionnaire administered to the general population, in order to assess attitudes, knowledge and behaviours around prevention and control of Zika infection. Methods A questionnaire was developed based on a comprehensive review of the extant literature, pre-existing questionnaires and experts focus groups. Results The final, validation version of the questionnaire comprised 8 items, with good psychometric properties (Cronbach’s alpha of 0.81). Overall test/re-test concordance was 0.86, ranging from 0.76 to 0.94 according to each item. Conclusion In conclusion, the questionnaire seems to be an appropriate and useful tool to detect cognitive gaps concerning behaviours responsible for possible transmissions of the disease, even in a non-endemic country such as Italy. Future analysis will explore the factorial structure of the questionnaire as well as knowledge, beliefs and attitudes concerning ZIKV among Italian general population

About cancer screenings and saving lives: measuring the effects of cancer screening programs through meta-analyses-A comment to the meta-analysis "Estimated Lifetime Gained With Cancer Screening Tests" by Bretthauer et al. (2023)

It is a matter of debate whether cancer-specific or all-cause mortality should be the principal measure to evaluate cancer screening efficacy

Cancer burden trends in Umbria region using a joinpoint regression

Introduction. The analysis of the epidemiological data on cancer is an important tool to control and evaluate the outcomes of primary and secondary prevention, the effectiveness of health care and, in general, all cancer control activities. Materials and methods. The aim of the this paper is to analyze the cancer mortality in the Umbria region from 1978 to 2009 and incidence from 1994-2008. Sex and sitespecific trends for standardized rates were analyzed by “joinpoint regression”, using the surveillance epidemiology and end results (SEER) software. Results. Applying the jointpoint analyses by sex and cancer site, to incidence spanning from 1994 to 2008 and mortality from 1978 to 2009 for all sites, both in males and females, a significant joinpoint for mortality was found; moreover the trend shape was similar and the joinpoint years were very close. In males standardized rate significantly increased up to 1989 by 1.23% per year and significantly decreased hereafter by -1.31%; among females the mortality rate increased in average of 0.78% (not significant) per year till 1988 and afterward significantly decreased by -0.92% per year. Incidence rate showed different trends among sexes. In males was practically constant over the period studied (not significant decrease 0.14% per year), in females significantly increased by 1.49% per year up to 2001 and afterward slowly decreased (-0.71% n.s. estimated annual percent change − EAPC). Conclusions. For all sites combined trends for mortality decreased since late ’80s, both in males and females; such behaviour is in line with national and European Union data. This work shows that, even compared to health systems that invest more resources, the Umbria public health system achieved good health outcomes

About cancer screenings and saving lives: measuring the effects of cancer screening programs through meta-analyses—A comment to the meta-analysis “Estimated Lifetime Gained With Cancer Screening Tests” by Bretthauer et al. (2023)

A meta-analysis of randomized clinical trials conducted by Bretthauer et al. to evaluate the advantage of cancer screening, recently published by Jama Internal Medicine, concluded that “common cancer screenings do not save lives with the possible exception of sigmoidoscopy screening” (1). The Authors derive their conclusion from estimates of lifetime gained with screening by “comparing all-cause mortality in people who underwent screening with those who did not.” They used the relative risk of death from any cause measured from randomized trials of cancer screenings and the average follow-up time of the unscreened group to obtain estimates of lifetime gained with screening. Both Bretthauer et al. in their meta-analysis and a comment paper appeared in the same number of JAMA Internal Medicine express the view that only randomized controlled trials can provide evidence of (cancer) screening efficacy and that a reduction of all-cause mortality is the measure of choice to evaluate efficacy (instead of the commonly used cancer-specific mortality) (1, 2). The reason for their choice is that a reduced risk of cancer specific deaths, if it is not associated with a reduced risk of all- cause mortality, can be considered the consequence of deaths associated with harmful effects of screening counterbalancing the screening benefit or of substitution of cancer specific deaths with death from competing causes. Nevertheless, we contend that the use of too stringent criteria led to an underestimation of the influence of screening on all-cause mortality in the meta-analysis authored by Bretthauer et al. and that the use of all-cause mortality implies small and unreliable estimates of screening efficacy (1). We believe that small estimates of relative risk for all-cause mortality should not be interpreted as minor effect of a cancer screening but indicate the opportunity to investigate the presence of bias in cause of death assignment and eventual harm of screening. With respect to the results published by Bretthauer et al., we also remark that 10–15 years of follow-up are insufficient to fully evaluate the impact of screening. Furthermore, low adherence to screening and uptake of screening in the control arm led to underestimation of screening efficacy in some randomized trials. Finally, evidence from observational studies should not be completely ignored, particularly for cancer screening that reduces incidence of infiltrative cancers