Effects of Colorectal Cancer Screening on Population Health: a modeling assessment

Colorectal cancer (CRC) is the second leading cause of cancer death in the Netherlands and other developed countries. Each year, more than 10,000 cases are newly diagnosed in the Netherlands and over 1 million worldwide. About half of these patients die of the disease. CRC is most common in Europe, North America, Australia and Japan (Figure 1.1). The Western diet is the most likely cause for the high incidence in these countries. This causation is supported by the increasing trend in CRC incidence in newly industrialized countries and the high CRC incidence in non‐Western immigrants in for example the U.S. and Australia

Utilization of surveillance after polypectomy in the Medicare population

Background: Surveillance in patients with previous polypectomy was underused in the Medicare population in 1994. This study investigates whether expansion of Medicare reimbursement for colonoscopy screening in high-risk individuals has reduced the inappropriate use of surveillance. Methods: We used Kaplan-Meier analysis to estimate time to surveillance and polyp recurrence rates for Medicare beneficiaries with a colonoscopy with polypectomy between 1998 and 2003 who were followed through 2008 for receipt of surveillance colonoscopy. Generalized Estimating Equations were used to estimate risk factors for: 1) failing to undergo surveillance and 2)

Attribution of Colonoscopy Risk Does Not FIT! Reply

Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Colorectal cancer risk after removal of polyps in fecal immunochemical test based screening

Background: Colonoscopy surveillance intervals are based on the predicted risk of metachronous colorectal cancer (CRC) after polyp removal. However, risk estimation per polyp subtype is difficult due to the fact that many patients have multiple polyps. To enable risk estimation per polyp subtypes we examined the metachronous CRC risk of subgroups based on presence or absence of co-occurring findings. Methods: Using high-quality screening colonoscopies performed after a positive fecal immunochemical test between 2014 and 2020 within the Dutch CRC screening program, we applied Cox regression analysis to evaluate the association between findings at baseline colonoscopy and metachronous CRCs. For our primary outcome, we appointed each patient to unique subgroups based on removed polyp subtypes that were present or absent at baseline colonoscopy and used the groups without polyps as reference. High-risk subgroups were individuals with high-risk serrated polyps, defined as serrated polyp ≥10 mm, sessile serrated lesions with dysplasia, or traditional serrated adenomas, as well as high-risk adenomas, defined as adenoma ≥10 mm or containing high-grade dysplasia. Findings: In total 253,833 colonoscopies were included. Over a median follow-up of 36 months (IQR, 21–57), we identified 504 metachronous CRCs. Hazard ratios for metachronous CRC was 1.70 (95% CI, 1.07–2.69) for individuals with high-risk serrated polyps without high-risk adenomas, 1.22 (0.96–1.55) for individuals with high-risk adenomas without high-risk serrated polyps, and 2.00 (1.19–3.39) for individuals with high-risk serrated polyps and high-risk adenomas, compared to patients without polyps. Interpretation: Accounting for co-occurring findings, we observed an increased metachronous CRC risk for individuals that had high-risk serrated polyps with the presence of high-risk adenomas, or individuals with high-risk serrated polyps without high-risk adenomas. These findings could provide more evidence to support post-polypectomy surveillance guidelines. Funding: None.</p

Modeling a high mass turn down in the stellar initial mass function

Statistical sampling from the stellar initial mass function (IMF) for all star-forming regions in the Galaxy would lead to the prediction of ~1000 Msun stars unless there is a rapid turn-down in the IMF beyond several hundred solar masses. Such a turndown is not necessary for dense clusters because the number of stars sampled is always too small. Here we explore several mechanisms for an upper mass cutoff, including an exponential decline of the star formation probability after a turbulent crossing time. The results are in good agreement with the observed IMF over the entire stellar mass range, and they give a gradual turn down compared to the Salpeter function above ~100 Msun for normal thermal Jeans mass, M_J. The upper mass turn down should scale with M_J in different environments. A problem with the models is that they cannot give both the observed power-law IMF out to the high-mass sampling limit in dense clusters, as well as the observed lack of supermassive stars in whole galaxy disks. Either there is a sharper upper-mass cutoff in the IMF, perhaps from self-limitation, or the IMF is different for dense clusters than for the majority of star formation that occurs at lower density. Dense clusters seem to have an overabundance of massive stars relative to the average IMF in a galaxy.Comment: 19 pages, 2 figures, Astrophysical Journal, Vol 539, August 10, 200

Reaction rate uncertainties and 26Al in AGB silicon carbide stardust

Stardust is a class of presolar grains each of which presents an ideally uncontaminated stellar sample. Mainstream silicon carbide (SiC) stardust formed in the extended envelopes of carbon-rich asymptotic giant branch (AGB) stars and incorporated the radioactive nucleus 26Al as a trace element. The aim of this paper is to analyse in detail the effect of nuclear uncertainties, in particular the large uncertainties of up to four orders of magnitude related to the 26Al_g+(p,gamma)27Si reaction rate, on the production of 26Al in AGB stars and compare model predictions to data obtained from laboratory analysis of SiC stardust grains. Stellar uncertainties are also briefly discussed. We use a detailed nucleosynthesis postprocessing code to calculate the 26Al/27Al ratios at the surface of AGB stars of different masses (M = 1.75, 3, and 5 M_sun) and metallicities (Z = 0.02, 0.012, and 0.008). For the lower limit and recommended value of the 26Al_g(p,gamma)27Si reaction rate, the predicted 26Al/27Al ratios replicate the upper values of the range of the 26Al/27Al ratios measured in SiC grains. For the upper limit of the 26Al_g(p,gamma)27Si reaction rate, instead, the predicted 26Al/27Al ratios are approximately 100 times lower and lie below the range observed in SiC grains. When considering models of different masses and metallicities, the spread of more than an order of magnitude in the 26Al/27Al ratios measured in stellar SiC grains is not reproduced. We propose two scenarios to explain the spread of the 26Al/27Al ratios observed in mainstream SiC, depending on the choice of the 26Al_g+p reaction rate. One involves different times of stardust formation, the other involves extra-mixing processes. Stronger conclusions will be possible after more information is available from future nuclear experiments on the 26Al_g+p reaction.Comment: 6 pages, 5 Postscript figures, accepted for publication in Astronomy and Astrophysic

Targeting Chemoprevention of Colorectal Cancer to Those Who Are Likely to Respond

In the past four decades, chemoprevention of colorectal cancer (CRC) has been the subject of many epidemiologic and intervention trials of naturally occurring or pharmacologic agents. Recently, the positioning of cyclooxygenase 2 inhibitors as a viable option in this context was a major breakthrough; however, it was hampered by adverse cardiovascular events. This review questions whether chemopreventive measures for CRC are ready to be used in mass or individual applications, standing alone or in combination with other CRC-preventive measures. It also discusses steps that may be undertaken to explore this field further

Multifractal Scaling, Geometrical Diversity, and Hierarchical Structure in the Cool Interstellar Medium

Multifractal scaling (MFS) refers to structures that can be described as a collection of interwoven fractal subsets which exhibit power-law spatial scaling behavior with a range of scaling exponents (concentration, or singularity, strengths) and dimensions. The existence of MFS implies an underlying multiplicative (or hierarchical, or cascade) process. Panoramic column density images of several nearby star- forming cloud complexes, constructed from IRAS data and justified in an appendix, are shown to exhibit such multifractal scaling, which we interpret as indirect but quantitative evidence for nested hierarchical structure. The relation between the dimensions of the subsets and their concentration strengths (the "multifractal spectrum'') appears to satisfactorily order the observed regions in terms of the mixture of geometries present: strong point-like concentrations, line- like filaments or fronts, and space-filling diffuse structures. This multifractal spectrum is a global property of the regions studied, and does not rely on any operational definition of "clouds.'' The range of forms of the multifractal spectrum among the regions studied implies that the column density structures do not form a universality class, in contrast to indications for velocity and passive scalar fields in incompressible turbulence, providing another indication that the physics of highly compressible interstellar gas dynamics differs fundamentally from incompressible turbulence. (Abstract truncated)Comment: 27 pages, (LaTeX), 13 figures, 1 table, submitted to Astrophysical Journa

Prevalence and Clinical Features of Sessile Serrated Polyps: A Systematic Review

Background & Aims: Sessile serrated polyps (SSPs) could account for a substantial proportion of colorectal cancers. We aimed to increase clarity on SSP prevalence and clinical features. Methods: We performed a systematic review of MEDLINE, Web of Science, Embase, and Cochrane databases for original studies published in English since 2000. We included studies of different populations (United States general or similar), interventions (colonoscopy, autopsy), comparisons (world regions, alternative polyp definitions, adenoma), outcomes (prevalence, clinical features), and study designs (cross-sectional). Random-effects regression was used for meta-analysis where possible. Results: We identified 74 relevant colonoscopy studies. SSP prevalence varied by world region, from 2.6% in Asia (95% confidence interval [CI], 0–5.9) to 10.5% in Australia (95% CI, 2.8–18.2). Prevalence values did not differ significantly between the United States and Europe (P = .51); the pooled prevalence was 4.6% (95% CI, 3.4–5.8), and SSPs accounted for 9.4% of polyps with malignant potential (95% CI, 6.6–12.3). The mean prevalence was higher when assessed through high-performance examinations (9.1%; 95% CI, 4.0–14.2; P = .04) and with an alternative definition of clinically relevant serrated polyps (12.3%; 95% CI, 9.3–15.4; P < .001). Increases in prevalence with age were not statistically significant, and prevalence did not differ significantly by sex. Compared with adenomas, a higher proportion of SSPs were solitary (69.0%; 95% CI, 45.9–92.1; P = .08), with diameters of 10 mm or more (19.3%; 95% CI, 12.4–26.2; P = .13) and were proximal (71.5%; 95% CI, 63.5–79.5; P = .008). The mean ages for detection of SSP without dysplasia, with any or low-grade dysplasia, and with high-grade dysplasia were 60.8 years, 65.6 years, and 70.2 years, respectively. The range for proportions of SSPs with dysplasia was 3.7%–42.9% across studies, possibly reflecting different study populations. Conclusions: In a systematic review, we found that SSPs are relatively uncommon compared with adenoma. More research is needed on appropriate diagnostic criteria, variations in detection, and long-term risk

Cost-effectiveness and budget impact analyses of a colorectal cancer screening programme in a high adenoma prevalence scenario using MISCAN-Colon microsimulation model

This economic evaluation showed a screening intervention with a major health gain that also produced net savings when a long follow-up was used to capture the late economic benefit. The number of colonoscopies required was high but remain within the capacity of the Basque Health Service. So far in Europe, no other population Colorectal Cancer screening programme has been evaluated by budget impact analysis