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 premalignant 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 –, fecal DNA) or directly by colonic inspection (flexible sigmoidoscopy, colonoscopy, CT colonography, 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 The use of colonoscopy as a screening test is increasing and this strategy has superseded all alternatives in the US and Germany.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 underused 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, CT colonography and capsule endoscopy is reviewed.
Fever plays a role in activating innate immunity while its relevance in activating adaptive immunity is less clear. Even brief exposure to elevated temperatures significantly impacts on the immunostimulatory capacity of dendritic cells (DCs), but the consequences on immune response remain unclear. To address this issue, we analyzed the gene expression profiles of normal human monocyte-derived DCs from nine healthy adults subjected either to fever-like thermal conditions (39°C) or to normal temperature (37°C) for 180 minutes. Exposure of DCs to 39°C caused upregulation of 43 genes and downregulation of 24 genes. Functionally, the up/downregulated genes are involved in post-translational modification, protein folding, cell death and survival, and cellular movement. Notably, when compared to monocytes, DCs differentially upregulated transcription of the secreted protein IGFBP-6, not previously known to be specifically linked to hyperthermia. Exposure of DCs to 39°C induced apoptosis/necrosis and resulted in accumulation of IGFBP-6 in the conditioned medium at 48 h. IGFBP-6 may have a functional role in the hyperthermic response as it induced chemotaxis of monocytes and T lymphocytes, but not of B lymphocytes. Thus, temperature regulates complex biological DC functions that most likely contribute to their ability to induce an efficient adaptive immune response.
Clostridioides difficile (C. difficile) is responsible for a high percentage of gastrointestinal infections and its pathological activity is due to toxins A and B. C. difficile infection (CDI) is increasing worldwide due to the unstoppable spread of C. difficile in the anthropized environment and the progressive human colonization. The ability of C. difficile toxin B to induce senescent cells and the direct correlation between CDI, irritable bowel syndrome (IBS), and inflammatory bowel diseases (IBD) could cause an accumulation of senescent cells with important functional consequences. Furthermore, these senescent cells characterized by long survival could push pre-neoplastic cells originating in the colon towards the complete neoplastic transformation in colorectal cancer (CRC) by the senescence-associated secretory phenotype (SASP). Pre-neoplastic cells could appear as a result of various pro-carcinogenic events, among which, are infections with bacteria that produce genotoxins that generate cells with high genetic instability. Therefore, subjects who develop IBS and/or IBD after CDI should be monitored, especially if they then have further CDI relapses, waiting for the availability of senolytic and anti-SASP therapies to resolve the pro-carcinogenic risk due to accumulation of senescent cells after CDI followed by IBS and/or IBD.
Month of birth influences the risk of developing several diseases. We investigated the influence of date of birth on melanoma skin cancer (MSC) and non-melanoma skin cancer (NMSC) incidence. Enhanced cancer registry data were analysed including 1751 MSC and 15 200 NMSC. People born in February to April showed significantly elevated risks of NMSC compared with those born in summertime. We demonstrated seasonality by date of birth for skin cancer incidence. Neonatal UV exposure may explain this finding.
Despite the well-recognised relevance of screening in colorectal cancer (CRC) control, adherence to screening is often suboptimal. Improving adherence represents an important public health strategy. We investigated the influence of family doctors (FDs) as determinant of CRC screening adherence by comparing each FDs practice participation probability to that of the residents in the same geographic areas using the whole population geocoded. We used multilevel logistic regression model to investigate factors associated with CRC screening adherence, among 333,843 people at their first screening invitation. Standardized Adherence Rates (SAR) by age, gender, and socioeconomic status were calculated comparing FDs practices to the residents in the same geographic areas using geocoded target population. Screening adherence increased from 41.0% (95% CI, 40.8–41.2) in 2006–2008 to 44.7% (95% CI, 44.5–44.9) in 2011–2012. Males, the most deprived and foreign-born people showed low adherence. FD practices and the percentage of foreign-born people in a practice were significant clustering factors. SAR for 145 (21.4%) FDs practices differed significantly from people living in the same areas. Predicted probabilities of adherence were 31.7% and 49.0% for FDs with low and high adherence, respectively. FDs showed a direct and independent effect to the CRC screening adherence of the people living in their practice. FDs with significantly high adherence level could be the key to adherence improvement. Most deprived individuals and foreigners represent relevant targets for interventions in public health aimed to improve CRC screening adherence.
People alive many years after breast (BC) or colorectal cancer (CRC) diagnoses are increasing. This paper aimed to estimate the indicators of cancer cure and complete prevalence for Italian patients with BC and CRC by stage and age. A total of 31 Italian Cancer Registries (47% of the population) data until 2017 were included. Mixture cure models allowed estimation of net survival (NS); cure fraction (CF); time to cure (TTC, 5‐year conditional NS >95%); cure prevalence (who will not die of cancer); and already cured (prevalent patients living longer than TTC). 2.6% of all Italian women (806,410) were alive in 2018 after BC and 88% will not die of BC. For those diagnosed in 2010, CF was 73%, 99% when diagnosed at stage I, 81% at stage II, and 36% at stages III–IV. For all stages combined, TTC was >10 years under 45 and over 65 years and for women with advanced stages, but ≤1 year for all BC patients at stage I. The proportion of already cured prevalent BC women was 75% (94% at stage I). Prevalent CRC cases were 422,407 (0.7% of the Italian population), 90% will not die of CRC. For CRC patients, CF was 56%, 92% at stage I, 71% at stage II, and 35% at stages III–IV. TTC was ≤10 years for all age groups and stages. Already cured were 59% of all prevalent CRC patients (93% at stage I). Cancer cure indicators by stage may contribute to appropriate follow‐up in the years after diagnosis, thus avoiding patients' discrimination.