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Li-Fraumeni syndrome (LFS) is a rare autosomal dominant inherited genetic disorder that greatly increases the risk of developing several types of cancer, including young children and young adults. LFS is primarily caused by specific mutations in the tumor suppressor gene TP53. In this study, we successfully generated two human induced pluripotent stem cell (iPSC) lines derived from patients diagnosed with LFS, each carrying a distinct heterozygous mutation in the TP53 gene. These LFS patient-derived iPSC lines exhibited robust expression of key pluripotency markers, demonstrated the capacity to differentiate into all three germ layers (endoderm, mesoderm, and ectoderm), and maintained a normal karyotype. The establishment of these iPSC lines provides a valuable tool for modeling LFS in vitro, enabling researchers to investigate the underlying pathological mechanisms associated with the disease across various cell types and tissues.

Background and Aims: The 2012 and 2020 US Multi-Society Task Force postpolypectomy guidelines have recommended progressively longer surveillance intervals for patients with low-risk adenomas (LRAs). These guidelines require data from past colonoscopies. We examined the impact of the 2012 guidelines for second surveillance on clinical practice, including the availability of prior colonoscopy data, with the aim of informing the implementation of the 2020 guidelines. Methods: We identified surveillance colonoscopies at Stanford Health Care and the Palo Alto Veterans Affairs Health Care System in 3 periods: preguideline (March–August 2012), postguideline (January–June 2013), and delayed postguideline (July–September 2017). We collected data on the most recent previous colonoscopy, findings at the study entry surveillance colonoscopy, and recommendations for subsequent surveillance. Results: Among 977 patients, the most recent prior colonoscopy data were available in 78% of preguideline, 78% of postguideline, and 61% of delayed postguideline cases (P < .001). The fraction of surveillance colonoscopy reports that deferred recommendations awaiting pathology increased from 6% to 11% in preguideline and postguideline to 59% in delayed postguideline cases (P < .001). Overall adherence to guidelines for subsequent surveillance was similar in all 3 periods (54%–67%; P = .089). In the postguideline and delayed postguideline periods combined, a 10-year subsequent surveillance interval was recommended in 0 of 29 cases with LRA followed by normal surveillance colonoscopy. Conclusion: In patients undergoing surveillance, prior colonoscopy data were not always available and recommendations were often deferred awaiting pathology. Adherence to subsequent surveillance guidelines was suboptimal, especially for LRA followed by normal colonoscopy. Strategies addressing these gaps are needed to optimize implementation of the updated 2020 postpolypectomy guidelines.

Abstract Background Colorectal cancer (CRC) remains a leading cause of cancer‐related death despite being highly preventable. Efforts to increase participation in CRC screening have not met national goals. We developed a novel approach: building a business case for philanthropic investment in CRC screening. Methods A taskforce representing the public health community, professional societies, charitable foundations, academia, and industry was assembled to: (a) quantify the impact of improving CRC screening rates; (b) identify barriers to screening; (c) estimate the “activation cost” to overcome barriers and screen one additional person; (d) develop a holistic business case that is attractive to philanthropists; and (e) launch a demonstration project. Results We estimated that of 50 600 CRC deaths annually in the US, 55% occur in 50‐ to 85‐year‐olds and are potentially addressable by improvements in CRC screening. Barriers to screening were identified in all patient journey phases, including lack of awareness or insurance and logistical challenges in the pre‐physician phase. The cost to activate one person to undergo screening was $25‐175. This translated into a cost of $6000‐36 000 per CRC death averted by philanthropic investment. Based on this work, the Colorectal Cancer Alliance launched the effort “March Forth” to prevent 100 000 CRC deaths in the US over 10 years, with the first pilot in Philadelphia. Conclusions A holistic business plan can attract philanthropy to promote CRC screening. A simple message of “You can save a life from CRC with a $25 000 donation” can motivate demonstration projects in regions with high CRC rates and low screening participation.

Background and study aims Patients with cirrhosis demonstrate alterations in physiology, hemodynamics, and immunity which may increase procedural risk. There exist sparse data regarding the safety of performing ambulatory colonoscopy in patients with cirrhosis. Patients and methods From a population-based sample of three North American states (California, Florida, and New York), we collected data on 3,590 patients with cirrhosis who underwent ambulatory colonoscopy from 2009 to 2014. We created a control cohort propensity score-matched for cirrhotic severity who did not undergo colonoscopy (N = 3,590) in order to calculate the attributable risk for adverse events. The primary endpoint was the rate of unplanned hospital encounters (UHEs) within 14 days of colonoscopy (or from a synthetic index date for the control cohort). Predictors for UHE were assessed in multivariable regression. Results The attributable risk for any UHE following colonoscopy was 3.1 % (confidence interval [CI] 2.1–4.1 %, P

Background and study aims: Colorectal cancer (CRC) screening strategies in Germany include guaiac-based fecal occult blood testing (gFOBT) starting at age 50 and a switch to colonoscopy at age 55 or continued gFOBT testing, but screening utilization is limited. Blood-based biomarkers, such as methylated Septin 9 DNA ( m SEPT9), may improve screening rates. We performed a cost-effectiveness analysis of current and emerging CRC screening strategies in Germany. Methods: Using a validated Markov model, we compared annual gFOBT for ages 50 through 54 followed by biennial testing until age 75 (FOBT) or by colonoscopy at ages 55 and 65 (FOBT/COLO 55,65), substitution of fecal immunochemical testing (FIT) for gFOBT (FIT, FIT/COLO 55,65), and annual or biennial plasma m SEPT9 testing. We also considered persons who utilize only colonoscopy and varied age at colonoscopy utilization. Results: The current strategies were more effective and less costly than no screening. FIT was more effective and less costly than m SEPT9 testing. FIT/COLO 55,65 cost €12 200 per quality-adjusted life-years gained in comparison with FIT. m SEPT9-based screening was cost-effective in comparison with no screening but was dominated by other cost-saving strategies. Differential screening utilization and adherence greatly affected incremental results between strategies. In probabilistic analyses, FIT was preferred in 49 % and FIT/COLO 55,65 in 47 % of iterations. Conclusion: Currently available CRC screening strategies in Germany, including hybrid fecal testing/colonoscopy, are likely to be cost-saving. Current strategies appear superior to m SEPT9-based screening. The impact of blood-based biomarkers is likely to depend on utilization and adherence as much as on test performance characteristics and cost.