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Background: Detection of cancer at the early stage currently offers the only viable strategy for reducing disease-related morbidity and mortality. Various approaches for multi-cancer early detection are being explored, which largely rely on capturing signals from circulating analytes shed by tumors into the blood. The fact that biomarker concentrations are limiting in the early stages of cancer, however, compromises the accuracy of these tests. We, therefore, adopted an alternate approach that involved interrogation of the serum metabolome with machine learning-based data analytics. Here, we monitored for modulations in metabolite patterns that correlated with the presence or absence of cancer. Results obtained confirmed the efficacy of this approach by demonstrating that it could detect a total of 15 cancers in women with an average accuracy of about 99%., Aims: To further increase the scope of our test, we conducted an investigator-initiated clinical trial involving a total of 6445 study participants, which included both cancer patients and non-cancer volunteers. Our goal here was to maximize the number of cancers that could be detected, while also covering cancers in both females and males., Methods and Results: Metabolites extracted from individual serum samples were profiled by ultra-performance liquid chromatography coupled to a high-resolution mass spectrometer using an untargeted protocol. After processing, the data were analyzed by our cancer detection machine-learning algorithm to differentiate cancer from non-cancer samples. Results revealed that our test platform could indeed detect a total of 30 cancers, covering both females and males, with an average accuracy of ~98%. Importantly, the high detection accuracy remained invariant across all four stages of the cancers., Conclusion: Thus, our approach of integrating untargeted metabolomics with machine learning-powered data analytics offers a powerful strategy for early-stage multi-cancer detection with high accuracy., Trial Registration: Registration No: CTRI/2023/03/050316., (© 2024 The Author(s). Cancer Reports published by Wiley Periodicals LLC.)

IFO'S communication campaign for the Italian Lung Screening Network (RISP) study, used multiple online and offline channels to engage not only smokers but a diverse audience. Out-reach activities and lifelong learning helped to promote healthy lifestyles, research findings and precision medicine. The campaign has increased the enrollment in the screening program, which in IFO, two years after 'start-up, is 3300. The pilot study targets smokers and former smokers aged 55 to 75, for prevention and early detection of lung cancer. Funded by the Ministry of Health, it involves 19 Italian centers to enroll 10,000 people. The ultimate goal is the inclusion of lung screening in the Essential Levels of Care (LEA) that is, the services that the National Health Service is required to provide to all citizens, free of charge. Subjects involved perform multilayer low-dose CT scan of the chest and blood sampling with liquid biopsy. The success of the campaign rewards the communication strategy, multidisciplinary collaboration, and activities always in synergy with the mission of the IFOs committed to: "spreading" clinical excellence; promoting citizen empowerment; considering correct information an institutional duty because it is part of treatment and prevention.

Objectives: With wide application of computed tomography (CT) in early lung cancer screening, solitary pulmonary nodules (SPNs) are frequently detected. Due to their high etiological diversity and potential for malignancy, rapid and accurate identification and malignant SPNs are crucial in the clinical management. In the present study, plasma exosomal microRNAs were identified and evaluated as sensitive and specific indicators for malignant SPNs., Materials and Methods: Exosomal miRNAs isolated from the plasmas of pathologically confirmed patients with SPN (four malignant and four benign, designated as the screening set) were subjected for high throughput sequencing and eight candidate miRNAs were selected. The pre-operation plasma levels of the candidate miRNAs in 77 patients with SPN (48 malignant and 29 benign, designated as the identification set) were detected by quantitative PCR, five miRNAs were identified as potential biomarkers for malignant SPNs, and the diagnostic values of the five miRNAs each alone or combined were then analyzed by AUROC analysis. The prediction values of the identified miRNAs were further evaluated in 95 patients with SPN (double blind, 74 malignant and 21 benign, designated as the validation set)., Results: High-throughput sequencing identified 45 miRNAs with statistical differences between benign and malignant SPNs. Among the eight candidate miRNAs in the identification set, miR-1-3p alone had the best diagnostic value, with the sensitivities and specificities of 89.6% and 100% for malignant SPNs. Unexpectedly, when miR-1-3p was combined with miR-99a-5p, both the sensitivity and specificity reached 100% for malignant SPNs. miR-1-3p+miR-125b-5p and miR-1-3p+miR-218-5p were also good indicators of malignant SPNs with sensitivities of 95.8% and 97.9%, specificities of 100% and 96.6%. Further analysis of these microRNA combinations in the validation set indicated that the PPV were 91.4%, 97.4%, and 93.5% and the NPV were 100%, 100%, and 88.9% for miR-1-3p+miR-99a-5p, miR-1-3p+miR-218-5p, and miR-1-3p+miR-125b-5p, with the sensitivities were 100%, 100%, and 97.3% and the specificities were 66.7%, 90.5%, and 76.2% for miR-1-3p+miR-99a-5p, miR-1-3p+miR-218-5p, and miR-1-3p+miR-125b-5p, respectively., Conclusions: Through high throughput sequencing, qPCR determination of plasma microRNAs and AUROC analysis, miR-1-3p combined with miR-99a-5p, miR-125b-5p, or miR-218-5p have been found to be sensitive and specific indicators of malignant SPNs in both the identification and validation sets. Our results indicate that the panels of plasma miRNAs can be used as diagnostic biomarkers for malignant SPNs., (© 2024 The Author(s). Clinical Respiratory Journal published by John Wiley & Sons Ltd.)

High-risk human papillomavirus (HR-HPV) testing, utilizing both DNA and RNA methods, offers enhanced sensitivity compared to cytology for detecting high-grade cervical intraepithelial neoplasia (CIN2+). Meanwhile, HR-HPV E6 and E7 mRNAs are more likely to differentiate the transient infection from the persistent than DNA. Aptima HPV can not only detect HPV mRNA but also HPV DNA though it is much more efficient at detecting HPV RNA than DNA. Currently, there are few studies on the distribution of HPV E6 and E7 mRNA and DNA in the same individual. It is interesting to compare the clinical performance of the Onclarity and Aptima HPV assays and to assess variations in viral load across different histological grades at both DNA and mRNA levels. The analysis included 1607 women (902 from a cervical cancer screening population and 705 inpatients and outpatients), with cervical cytological samples tested using the Aptima and Onclarity HPV assays. Both assays demonstrated high agreement for HPV types 18/45 and 16. Signal-to-cutoff (S/CO) values and Ct values for various HR-HPV types increased with histological severity from normal tissue to cancer. Notably, HPV18 Ct values exceeded those for HPV16 and 45 in women with ≥ CIN1 lesions but decreased sharply in cancer cases. Across the screening population, both assays showed similar sensitivity and predictive values for detecting CIN2+ lesions. The area under the curve (AUC) for CIN2+ and CIN3+ detection in the study population was robust (CIN2+: 0.880, 0.863; CIN3+: 0.881, 0.863). The DNA level for various HR-HPV types increased with histological severity from normal tissue to cancer, which might impact the performance of Aptima HPV assay. Both assays showed similar sensitivity and predictive values for detecting CIN2+ lesions., (© 2024 Wiley Periodicals LLC.)

Introduction: Individuals who develop new-onset diabetes have been identified as a high-risk cohort for pancreatic cancer (PC), exhibiting an incidence rate nearly 8 times higher than the general population. Hence, the targeted screening of this specific cohort presents a promising opportunity for early pancreatic cancer detection. We aimed to develop and validate a novel model capable of identifying high-risk individuals among those with new-onset diabetes., Methods: Employing the UK Biobank cohort, we focused on those developing new-onset diabetes during follow-up. Genetic and clinical characteristics available at registration were considered as candidate predictors. We conducted univariate regression analysis to identify potential indicators and used a 5-fold cross-validation method to select optimal predictors for model development. Five machine learning algorithms were used for model development., Results: Among 12,735 patients with new-onset diabetes, 100 (0.8%) were diagnosed with PC within 2 years. The final model (area under the curve, 0.897; 95% confidence interval, 0.865-0.929) included 5 clinical predictors and 24 single nucleotide polymorphisms. Two threshold cut-offs were established: 1.28% and 5.26%. The recommended 1.28% cut-off, based on model performance, reduces definitive testing to 13% of the total population while capturing 76% of PC cases. The high-risk threshold is 5.26%. Utilizing this threshold, only 2% of the population needs definitive testing, capturing nearly half of PC cases., Conclusions: We, for the first time, combined clinical and genetic data to develop and validate a model to determine the risk of pancreatic cancer in patients with new-onset diabetes using machine learning algorithms. By reducing the number of unnecessary tests while ensuring that a substantial proportion of high-risk patients are identified, this tool has the potential to improve patient outcomes and optimize healthcare sources., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Background Studies suggest that readers experience perceptual adaptation when interpreting batched screening mammograms, which may serve as a mechanism for improved performance. Purpose To analyze clinical digital breast tomosynthesis (DBT) screening data to evaluate changes in reader performance during sequential batch reading. Materials and Methods This observational retrospective study used data from the radiology information system collected for screening DBT examinations performed from January 2018 to December 2019. The reference standard was established based on pathology results, if applicable, or imaging findings at 1-year follow-up. Examinations were aggregated into batches, defined as a sequence of cases for a given reader with differences in interexamination time of 10 minutes or less. Mixed-effect models were used to evaluate performance and timing across batch positions. Statistical adjustments accounted for potential confounders, including patient characteristics (age, breast density), reading factors (day of week, time of day), and between-reader heterogeneity. Results The dataset included 121 652 examinations (median patient age, 61 years [IQR, 53-69 years]), including 1081 cancers interpreted by 15 radiologists. Unadjusted false-positive rates decreased from an averaged 15.5% at the first within-batch examination to 10.5% after three sequentially read examinations ( P < .001), without a significant change in sensitivity (82.6% vs 84.2%; P = .15). The interpretation time consistently decreased, achieving a substantial reduction in longer batches (average 2.8 to 2.2 minutes for noncancer examinations; P < .001). Adjustment for sampling bias and confounders (patient age, breast density, day of week, time of day; all P < .005) reduced the effect on false-positive rates (11.5% to 9.4% after three examinations; P < .001) and interpretation time (3.2 to 2.7 minutes for noncancer examinations; P < .001). Conclusion Radiologists showed improved recall rates and interpretation times without change in sensitivity over the course of batch reading of DBT screening examinations. © RSNA, 2024 See also the editorial by Iima and Satake in this issue.

One-dose prophylactic HPV vaccination of pre-adolescents may reduce cervical cancer deaths dramatically in lower-resource settings, but the benefits of achieving immediate high coverage among pre-adolescents would not be realized for 20 to 40 years. Prophylactic vaccine efficacy is reduced after sexual debut, and current therapeutic intervention candidates designed to treat existing HPV infections or precancerous lesions have yielded insufficient evidence to warrant widespread use. However, we are developing a feasible, scalable, high-quality cervical screening approach that could prevent hundreds of thousands of deaths, while we work to achieve high coverage of one-dose vaccination for adolescent cohorts. A time-limited "one screen" campaign approach for lower-resource settings could complement parallel efforts to achieve high coverage with one-dose vaccination. This screen-triage-treat strategy would target the highest risk groups of screening age (ie, 25 to 49 years) for once-in-a-lifetime HPV testing of self-collected samples using a low-cost accurate HPV test; subsequent triage relying on extended genotyping and a validated deep-learning algorithm for automated visual evaluation (AVE) would stratify management based on risk to provide treatment for those most likely to develop cancer without overburdening health care systems. Early efficacy of this approach has been demonstrated in 9 countries within the HPV-AVE (PAVE) Study Consortium. We estimate that the cost per death averted of a screen-triage-treat campaign is of similar magnitude to prophylactic vaccination. We do not envision perpetual investment in ubiquitous brick-and-mortar screening programs if "one dose, one screen" is implemented with high coverage and targets the highest-risk populations. In collaboration with in-country stakeholders, efforts to ensure acceptability, risk communication, and cost-effectiveness are underway., (Published by Oxford University Press 2024.)

Background Breast nonmass lesions (NMLs) are observed at screening and diagnostic US. However, knowledge is limited on imaging features of NMLs at screening US. Purpose To identify features of NMLs at screening US that are suspicious for malignancy based on mammographic findings. Materials and Methods This retrospective, multicenter study included asymptomatic women who underwent screening US between January 2012 and December 2019. Eligible women had NMLs at US, concurrent screening mammography, and record of a final diagnosis. Logistic regression analyses were used to identify factors associated with malignancy. The diagnostic performance of each sonographic feature according to mammographic findings was calculated. A reader study was performed to assess interreader agreement for sonographic features. Results Among 993 NMLs in 993 patients (mean age, 50 years ± 9 [SD]), 914 (92.0%) were benign and 79 (8.0%) were malignant. Mean size was larger for malignant NMLs than for benign NMLs (2.6 cm ± 1.1 vs 1.9 cm ± 0.8; P < .001). In multivariable analysis, associated calcifications (odds ratio [OR], 21.6 [95% CI: 8.0, 58.2]; P < .001), posterior shadowing (OR, 6.9 [95% CI: 2.6, 18.4]; P < .001), segmental distribution (OR, 6.2 [95% CI: 2.7, 14.4]; P < .001), mixed echogenicity (OR, 5.0 [95% CI: 1.8, 14.0]; P < .001), and size (OR, 1.5 [95% CI: 1.1, 2.1]; P = .01) at US were associated with malignancy. Associated calcifications, posterior shadowing, segmental distribution, and mixed echogenicity showed positive predictive values (PPVs) of 44%, 22%, 22.9%, and 16.6%, respectively. Having a negative mammogram was associated with a lower malignancy rate (2.8% vs 28.8%) and lower PPVs for sonographic features (0.7%-10.4% vs 24%-55%) than having a positive mammogram. Interreader agreement for sonographic features was good to excellent (Fleiss κ 95% CI lower bound range, 0.63-0.81). Conclusion Calcifications, posterior shadowing, segmental distribution, and mixed echogenicity associated with NMLs can be considered suspicious features for malignancy at screening US. As malignancy rates and PPVs differ according to mammographic abnormalities, combined assessment is mandatory. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Grimm in this issue.

Biomarkers are molecules such as proteins, genes, or other substances that may be tested to determine the stage of the tumor in a patient. The role of prostate cancer biomarkers is pivotal and the combination of prostate cancer immunotherapy with efficient biomarkers has emerged as a beneficial treatment strategy and its use has increased rapidly. The two primary objectives of this current prostate cancer early detection programs were recognizing non-symptomatic individuals with prostate cancer requiring prostatic core biopsy and identifying men with prostate cancer who might benefit from definitive medical treatment. The progress that has been made so far in the identification of the biomarkers that can be used for the classification, prediction and prognostication of prostate cancer, and as major targets for its clinical intervention has been well summarized in this review., Competing Interests: The authors have nothing to disclose., (© The Korean Urological Association.)

The risk of developing cervical cancer is not equal across populations-individual health history, economic, political, and societal factors influence cervical cancer risk. Certain health conditions, including human immunodeficiency virus (HIV) infection, immunosuppression, and history of high-grade cervical dysplasia, are associated with higher cervical cancer risk and warrant distinct screening, surveillance, and management guidelines. It is imperative for clinicians to recognize high-risk groups and apply appropriate corresponding guidelines. However, this can be difficult in practice, as recommendations regularly evolve. This review offers up-to-date guidance in a case-based format on cervical cancer screening, surveillance, and management for high-risk patients., (Copyright © 2024 The Cleveland Clinic Foundation. All Rights Reserved.)

Objectives: The reasons for and incidence of delay in screening colonoscopies during the coronavirus disease 2019 (COVID-19) pandemic are of major public health interest. The risks and reasons for delay likely vary between public and private institutions. This research sought to analyze data regarding the completion of screening colonoscopies after a positive fecal immunochemical test (FIT) before and during the COVID-19 pandemic and the reasons for a delay in obtaining these results at the Lt. Col. Luke Weathers, Jr. Veterans Affairs Medical Center. The goals were to evaluate the institutional resilience and analyze the problems associated with this major healthcare crisis., Methods: This closed cohort study included all positive FITs from our local Veterans Affairs (VA) medical center from October 2019 to January 2020 and July 2020 to May 2021. A total of 115 VA patients with a positive FIT prepandemic and 157 VA patients with a positive FIT during the pandemic were included. Completion rates within 180 days were measured, and charts were reviewed to identify the reasons for lack of completion. Both community and local VA procedures for veterans were included. Univariate and multivariable analyses were applied to calculate odds ratios (ORs). The Pearson χ 2 test was applied to calculate P values., Results: VA patients' percentage of timely completion was lower pre-COVID-19 than it was during the pandemic, and the percentage of delayed completion was higher pre-COVID-19 than it was during the pandemic. Comparing patients who completed a colonoscopy with those who did not, increasing age had an OR of 0.947 (95% CI 0.920-0.975), and White race had an OR of 0.504 (95% CI 0.291-0.873). Evaluating delays in colonoscopy completion, VA colonoscopies versus referral to the community had an OR of 4.472 (95% CI 1.602-12.483), and pre-COVID-19 completion versus during COVID-19 had an OR of 4.663 (95% CI 1.727-12.594) with multivariable logistic regression., Conclusions: There was a statistically significant increase in timely colonoscopy completion during the study period when compared with the pre-COVID-19 period. The completion rate was higher at the Lt. Col. Luke Weathers, Jr. VA Medical Center than a large population average in 2020, possibly related to community colonoscopies and an aggressive case management system. In addition, increasing age and White race were associated with decreased colonoscopy completion. Predictors of an increased delay in colonoscopy completion included a pre-COVID-19 positive FIT and colonoscopies performed within the VA rather than being referred to providers in the community. A common reason for delay in all of the groups was patients declining intervention and delay/lack of referral.

Background: The increasing incidence of endometrial cancer (EC) has highlighted the need for improved early detection methods. This study aimed to develop and validate a novel DNA methylation classifier, EMPap, for EC detection using cervical scrapings., Methods: EMPap incorporated the methylation status of BHLHE22 and CDO1, along with age and body mass index (BMI), into a logistic regression model to calculate the endometrial cancer methylation (EM) score for identifying EC in cervical scrapings. We enrolled 1297 patients with highly suspected EC, including 196 confirmed EC cases, and assessed the EMPap performance in detecting EC., Results: EMPap demonstrated robust diagnostic accuracy, with an area under the curve of 0.93, sensitivity of 90.3%, and specificity of 89.3%. It effectively detected EC across various disease stages, grades, and histological subtypes, and consistently performed well across patient demographics and symptoms. EMPap correctly identified 87.5% of the type II ECs and 53.8% of premalignant lesions. Notably, compared with transvaginal ultrasonography (TVS) in patients with postmenopausal bleeding, EMPap exhibited superior sensitivity (100% vs. 82.0%) and specificity (85.2% vs. 38.5%). In asymptomatic postmenopausal women, EMPap maintained high sensitivity (89.5%) and negative predictive value (NPV) (98.3%)., Conclusions: This study demonstrated the potential of EMPap as an effective tool for EC detection. Despite the limited sample size, EMPap showed promise for identifying type II EC and detecting over 50% of premalignant lesions. As a DNA methylation classifier, EMPap can reduce unnecessary uterine interventions and improve diagnosis and outcomes., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

The objective of this investigation was to improve the diagnosis of breast cancer by combining two significant datasets: the Wisconsin Breast Cancer Database and the DDSM Curated Breast Imaging Subset (CBIS-DDSM). The Wisconsin Breast Cancer Database provides a detailed examination of the characteristics of cell nuclei, including radius, texture, and concavity, for 569 patients, of which 212 had malignant tumors. In addition, the CBIS-DDSM dataset-a revised variant of the Digital Database for Screening Mammography (DDSM)-offers a standardized collection of 2,620 scanned film mammography studies, including cases that are normal, benign, or malignant and that include verified pathology data. To identify complex patterns and trait diagnoses of breast cancer, this investigation used a hybrid deep learning methodology that combines Convolutional Neural Networks (CNNs) with the stochastic gradients method. The Wisconsin Breast Cancer Database is used for CNN training, while the CBIS-DDSM dataset is used for fine-tuning to maximize adaptability across a variety of mammography investigations. Data integration, feature extraction, model development, and thorough performance evaluation are the main objectives. The diagnostic effectiveness of the algorithm was evaluated by the area under the Receiver Operating Characteristic Curve (AUC-ROC), sensitivity, specificity, and accuracy. The generalizability of the model will be validated by independent validation on additional datasets. This research provides an accurate, comprehensible, and therapeutically applicable breast cancer detection method that will advance the field. These predicted results might greatly increase early diagnosis, which could promote improvements in breast cancer research and eventually lead to improved patient outcomes., (© 2024. The Author(s).)

Annual low-dose CT screening of individuals with a smoking history identifies early curable lung tumors and reduces cancer mortality by 20%, yet only a minority of eligible patients undergo such monitoring. Mazzone and colleagues apply a blood-based cfDNA fragmentomic assay as a high-sensitivity/low-specificity pre-screen to help stratify individuals who may benefit most from more definitive low-dose CT imaging. See related article by Mazzone et al., p. 2224., (©2024 American Association for Cancer Research.)

Current strategies for early cancer detection and diagnosis need updating to achieve greater precision, necessitating the creation of a comprehensive evolutionary map of tumorigenesis. This requires establishing high-quality prospective cohorts, systematically collecting samples for integrated spatiotemporal multiomics analyses, and efficiently translating laboratory findings into clinical applications., (©2024 American Association for Cancer Research.)

Background/aim: Lung cancer remains a leading cause of cancer-related mortality worldwide, necessitating the development of effective early diagnostic strategies. Despite advancements in imaging and screening technologies, late-stage diagnoses remain common, limiting treatment options and reducing survival rates. Thus, there is a critical need for reliable, minimally invasive biomarkers to improve early detection and patient outcomes. Plasma protein biomarkers offer promising potential for early lung cancer detection and continuous disease monitoring. This study explored the potential of specific plasma protein markers as early indicators of lung cancer., Patients and Methods: Plasma samples were collected from normal healthy individuals and lung cancer patients, and protein purification and analysis were conducted using LC-MS/MS. A mixed-effect model was applied to select lung cancer-related protein markers based on label-free relative quantification values., Results: We identified 29 proteins with potential for early lung cancer diagnosis, including complement proteins (CFB, C3, C8G, C1QA, C1R, C6), orosomucoid proteins (ORM1, ORM2), ceruloplasmin (CP), alpha-1-B glycoprotein (A1BG), and others. These proteins play diverse roles in immune response, inflammation, and cell signaling, suggesting their relevance in lung cancer pathophysiology., Conclusion: Our findings suggest the potential of plasma proteins as early diagnostic biomarkers for lung cancer. Further validation in larger cohorts is needed to confirm their clinical utility. Integrating these biomarkers into existing diagnostic modalities could enhance early detection accuracy, leading to improved patient outcomes., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Introduction: Multicancer detection tests (MCDs) are blood-based tests designed to detect multiple cancer types. It is currently unclear whether these cancer screening tests improve mortality. To understand awareness of MCDs among providers and patients, as well as explore how they perceive the benefits, harms, and acceptability of MCDs, we have undertaken a focus group study in primary care physicians (PCPs) and laypersons to explore knowledge, attitudes, and expectations of cancer screening using MCDs., Methods: We conducted six focus groups with 45 PCP participants and 12 focus groups with 80 layperson participants. Participants were identified via a consumer research firm and found eligible following the completion of a screener survey. Moderators used a semi-structured guide containing open-ended questions and prompts to facilitate the discussion. Recordings were transcribed and coded line by line using a codebook developed based on questions and emerging discussion concepts, and emergent themes were identified., Results: Both PCP and layperson participants felt the that benefits of MCDs included ease of use and potential ability to detect cancers early. However, they felt that additional data is needed to overcome some of the concerns related to MCDs. PCP participants expressed concerns related to lack of practice guidelines, cost of diagnostic follow-ups, privacy and insurance issues, fear/anxiety related to confirmation of MCD results, and malpractice liability related to perceived false negative test results. Layperson participants expressed concerns related to costs, insurance coverage, and privacy, as well as anxiety over the confirmation of a positive test result., Conclusions: There is a major need for more rigorous data regarding MCDs to inform the development of guidelines for use as cancer screening tools., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Integrating artificial intelligence (AI) into mammography screening can support radiologists and improve programme metrics, yet the potential of different strategies for integrating the technology remains understudied. We compared programme-level performance metrics of seven AI integration strategies., Methods: We performed a retrospective comparative evaluation of seven strategies for integrating AI into mammography screening using datasets generated from screening programmes in Germany (n=1 657 068), the UK (n=223 603) and Sweden (n=22 779). The commercially available AI model used was Vara version 2.10, trained from scratch on German data. We simulated the performance of each strategy in terms of cancer detection rate (CDR), recall rate, and workload reduction, and compared the metrics with those of the screening programmes. We also assessed the distribution of the stages and grades of the cancers detected by each strategy and the AI model's ability to correctly localise those cancers., Findings: Compared with the German screening programme (CDR 6·32 per 1000 examinations, recall rate 4·11 per 100 examinations), replacement of both readers (standalone AI strategy) achieved a non-inferior CDR of 6·37 (95% CI 6·10-6·64) at a recall rate of 3·80 (95% CI 3·67-3·93), whereas single reader replacement achieved a CDR of 6·49 (6·31-6·67), a recall rate of 4·01 (3·92-4·10), and a 49% workload reduction. Programme-level decision referral achieved a CDR of 6·85 (6·61-7·11), a recall rate of 3·55 (3·43-3·68), and an 84% workload reduction. Compared with the UK programme CDR of 8·19, the reader-level, programme-level, and deferral to single reader strategies achieved CDRs of 8·24 (7·82-8·71), 8·59 (8·12-9·06), and 8·28 (7·86-8·71), without increasing recall and while reducing workload by 37%, 81%, and 95%, respectively. On the Swedish dataset, programme-level decision referral increased the CDR by 17·7% without increasing recall and while reducing reading workload by 92%., Interpretation: The decision referral strategies offered the largest improvements in cancer detection rates and reduction in recall rates, and all strategies except normal triaging showed potential to improve screening metrics., Funding: Vara., Competing Interests: Declaration of interests ZVF, MB, TM, VŠ, SB, and CL are current or former employees of Vara, with stock options as part of the standard compensation package. FJG, NRP, and SEH have research collaborations with Vara, ScreenPoint, Lunit, Google, Volpara, iCAD, Therapixel, CureMetrix, Sunnybrook Research Institute, and Massachusetts Institute of Technology., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Early and accurate diagnosis of gastric cancer (GC) is essential for reducing mortality and improving patient well-being. However, methods for the early diagnosis of GC are still lacking. In this study, by isobaric tagging for relative and absolute quantitation (iTRAQ), we identified 336 proteins that overlapped among the upregulated differentially expressed proteins (DEPs) in early gastric cancer (EGC) versus progressive gastric cancer (PGC), upregulated DEPs in EGC versus nongastric cancer (NGC), and nonsignificant proteins in EGC versus NGC. These DEPs were involved primarily in the neutrophil-related immune response. Network analysis of proteins and pathways revealed that fibrinogen α (FGA), β (FGB), and γ (FGG) are candidates for distinguishing EGC. Furthermore, parallel reaction monitoring (PRM), immunohistochemistry (IHC), and Western blot (WB) assays of clinical samples confirmed that, compared with that in PGC and NGC, only FGG was uniquely and significantly upregulated in the gastric mucosa of EGC. Our results demonstrated that FGG in the gastric mucosa could be a novel biomarker to diagnose EGC patients via endoscopy.

Background: In prior randomised controlled trials, lung cancer screening using low-dose computed tomography (LDCT) has been shown to reduce lung cancer mortality and overall mortality. Despite these results, organised screening in France remains a challenge. This study assessed the feasibility and efficacy of lung cancer screening within a real-life context in a French administrative territory., Methods: DEP KP80 was a single-arm prospective study. Participants aged between 55 and 74 years, smokers or former smokers of ≥30 pack-years, were recruited. An annual LDCT scan was scheduled and three rounds were performed. Subjects were selected by general practitioners or pulmonologists, who checked the inclusion criteria and prescribed the CT scan., Findings: Between March 2016 and February 2020, 1254 participants were enrolled. Overall, 945 (75.4%) participants underwent baseline LDCT (T0), 376 (42.8%) completed the first round (T1) and 270 (31%) the second (T2) one. Forty-two lung cancers were diagnosed, 30 cancers (71.4%) were stage I or II and 34 cancers (80.9%) were treated surgically. In this study, the overall positive predictive value for a positive screening was 48% (95% CI 37-59) and the negative predictive value 100% (95% CI 100-100)., Interpretation: This study demonstrated the feasibility and efficacy of lung cancer screening in a real-life context with most lung cancers diagnosed at an early stage and surgically removed. Our results also highlighted the importance of participation in each round, underlining the fact that optimising organisation is a major goal., Funding: Agence Régionale de Santé de Picardie, La Ligue contre le cancer, le Conseil Départemental de la Somme, and AstraZeneca., Competing Interests: Declaration of interests NS, DB, VJ, JdB, VP, BM, PB, MA and AL declare no potential conflicts of interest. SC declares grants from AstraZeneca, Amgen, Adene, BDbioscience, BMS, Boeringher, Chugai, Janssens, Laidet, Lilly, MSD, Novartis, Roche, Pfizer, Takeda, Volition and Transdiag, royalties from Volition, payment for expert testimony from Amgen, Astra Zeneca, Boeringher, Health Event, MSD, Novartis, Pfizer and Sanofi, and support for attending meetings from Amgen, Astra Zeneca, BMS, Chugai, Janssens, Laidet and Takeda. OL declares grants from Chiesi, AstraZeneca, BMS and Amgen, and support for attending meetings from France Oxygene and Aeris., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide. Early detection of HCC is a key factor in enabling curative therapies and improving overall survival. Worldwide, several guidelines are available for surveillance of at-risk populations and diagnosis of HCC. This article provides a current comprehensive update on screening and diagnosis of HCC., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The following is an overview of the numerous efforts to reduce access for women to breast cancer screening. Misinformation has been promoted over the many years to suggest that screening only works for women aged 50 years and over. In fact, there are no, scientifically derived data, to support the use of the age of 50 years as a threshold for screening. The randomized, controlled trials have proved that screening saves lives for women aged 40 to 74 years (the age of the women who participated)., Competing Interests: Disclosure Royalties from IZI Medical for Kopans localization system. Advisor to DART Imaging in China. Advisor to Malcova Imaging developing CT for the breast., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Multiple initiatives aim to develop circulating tumour DNA (ctDNA) tests for early cancer detection in asymptomatic individuals. The few studies describing ctDNA-testing in both asymptomatic and symptomatic patients report lower ctDNA detection in the asymptomatic patients. Here, we explore if asymptomatic patients differ from symptomatic patients e.g. by including a 'low-ctDNA-shedding' and 'less-aggressive' subgroup., Methods: ctDNA assessment was performed in two independent cohorts of consecutively recruited patients with asymptomatic colorectal cancer (CRC) (Cohort#1: n = 215, Cohort#2: n = 368) and symptomatic CRC (Cohort#1: n = 117, Cohort#2: n = 722)., Results: After adjusting for tumour stage and size, the odds of ctDNA detection was significantly lower in asymptomatic patients compared to symptomatic patients (Cohort#1: OR: 0.4, 95%CI: 0.2-0.8, Cohort#2: OR: 0.7, 95%CI: 0.5-0.9). Further, the recurrence risk was lower in asymptomatic patients (Cohort#1: sHR: 0.6, 95%CI: 0.3-1.2, Cohort#2: sHR: 0.6, 95%CI: 0.4-1.0). Notably, ctDNA-negative asymptomatic patients had the lowest recurrence risk compared to the symptomatic patients (Cohort#1: sHR: 0.2, 95%CI: 0.1-0.6, Cohort#2: sHR: 0.3, 95%CI: 0.2-0.6)., Conclusions: Our study suggests that asymptomatic patients are enriched for a 'low-ctDNA-shedding-low-recurrence-risk' subgroup. Such insights are needed to guide ctDNA-based early-detection initiatives and should prompt discussions about de-escalation of therapy and follow-up for ctDNA-negative asymptomatic CRC patients., Competing Interests: Competing interests The authors declare no competing interests. Ethics approval and consent to participate All participants provided informed consent and the study was approved by the Danish Committees on Health Research Ethics (j. no 1-10-72-223-14, H-4-2013-050, and 1-10-72-3-18) and reported according to STROBE guidelines [36]., (© 2024. The Author(s).)

Early cancer diagnosis from bisulfite-treated cell-free DNA (cfDNA) fragments requires tedious data analytical procedures. Here, we present a deep-learning-based approach for early cancer interception and diagnosis (DECIDIA) that can achieve accurate cancer diagnosis exclusively from bisulfite-treated cfDNA sequencing fragments. DECIDIA relies on transformer-based representation learning of DNA fragments and weakly supervised multiple-instance learning for classification. We systematically evaluate the performance of DECIDIA for cancer diagnosis and cancer type prediction on a curated dataset of 5389 samples that consist of colorectal cancer (CRC; n = 1574), hepatocellular cell carcinoma (HCC; n = 1181), lung cancer (n = 654), and non-cancer control (n = 1980). DECIDIA achieved an area under the receiver operating curve (AUROC) of 0.980 (95% CI, 0.976-0.984) in 10-fold cross-validation settings on the CRC dataset by differentiating cancer patients from cancer-free controls, outperforming benchmarked methods that are based on methylation intensities. Noticeably, DECIDIA achieved an AUROC of 0.910 (95% CI, 0.896-0.924) on the externally independent HCC testing set in distinguishing HCC patients from cancer-free controls, although there was no HCC data used in model development. In the settings of cancer-type classification, we observed that DECIDIA achieved a micro-average AUROC of 0.963 (95% CI, 0.960-0.966) and an overall accuracy of 82.8% (95% CI, 81.8-83.9). In addition, we distilled four sequence signatures from the raw sequencing reads that exhibited differential patterns in cancer versus control and among different cancer types. Our approach represents a new paradigm towards eliminating the tedious data analytical procedures for liquid biopsy that uses bisulfite-treated cfDNA methylome., (© 2024 The Author(s). Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Objectives: In 2021, the World Health Organisation (WHO) updated its guidelines for cervical screening from cytology testing to primary high-risk human papillomavirus (HR-HPV) testing. This change in testing has effectively led to a 'new disease' as women are now aware of having a virus that induces changes that can cause cancer, which they would have been unaware of previously. While current management involves a 'watch and wait' approach and no active treatment, the anxiety associated with having HR-HPV may prompt some women to seek 'treatments' outside the screening programme. ● to identify potential treatment options available for women with persistent HR-HPV and/or low-grade cervical intraepithelial neoplasia (CIN), i.e. ≤CIN 1. ● to determine the clinical effectiveness of these treatments, namely by: ◦ HR-HPV clearance rate, and/or: ◦ CIN regression., Methods: We searched MEDLINE, PubMed, EMBASE, Web of Science and the Cochrane Library. We included cohort studies and randomised controlled trials (RCTs) only. Records (n = 2135) were screened in Rayyan by two independent reviewers. Quality assessment was conducted using the ROBINS-I tool and the ROB-2 tool., Results: 12 studies (four cohort studies and eight RCTs) were included: six oral medications, two topical medications, one vaccination, and three non-surgical device treatments. Meta-analysis revealed that some therapeutic interventions, including vaginal gels, photodynamic therapy, and some oral medications, may lead to earlier resolution of persistent HR-HPV and regression of low-grade CIN when compared with natural clearance., Conclusion: This review can better inform discussions with HR-HPV+ women and answer their questions about alternatives to surveillance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Breast cancer remains a leading cause of cancer mortality worldwide, with early detection crucial for improving outcomes. This systematic review evaluates recent advances in portable non-invasive technologies for early breast cancer detection, assessing their methods, performance, and potential for clinical implementation. A comprehensive literature search was conducted across major databases for relevant studies published between 2015 and 2024. Data on technology types, detection methods, and diagnostic performance were extracted and synthesized from 41 included studies. The review examined microwave imaging, electrical impedance tomography (EIT), thermography, bioimpedance spectroscopy (BIS), and pressure sensing technologies. Microwave imaging and EIT showed the most promise, with some studies reporting sensitivities and specificities over 90 %. However, most technologies are still in early stages of development with limited large-scale clinical validation. These innovations could complement existing gold standards, potentially improving screening rates and outcomes, especially in underserved populations, whiles decreasing screening waiting times in developed countries. Further research is therefore needed to validate their clinical efficacy, address implementation challenges, and assess their impact on patient outcomes before widespread adoption can be recommended., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Childhood central nervous system (CNS) tumors tend to have a longer time interval until diagnosis than other pediatric malignancies. The aim is to describe the time to diagnosis among Brazilian pediatric patients treated at a tertiary center and explore associated factors., Methods: Cross-sectional study; application of questionnaires to parents of children with CNS tumors during outpatient visit or inpatient care., Results: One hundred parents participated between August and November 2023. The median age of the children at diagnosis was 7.2 years old. Low-grade glioma (LGG) was the most common tumor type (37%), followed by medulloblastoma (24%). The most frequent symptoms were morning and/or persistent vomiting and headache. The mean prediagnostic symptomatic interval (PSI) was 150 days. The mean parental interval was shorter than the medical (58.1 days vs 92.8 days). LGGs and tumors located in the central area had longer intervals to diagnosis than other tumors (296 vs 54 days) (p = 0.005) and (206 vs 155 days) (p = 0.007), respectively. Despite 81% of the patients undergoing pediatric routine follow-up, 87% of them had been diagnosed at an emergency department. Children attended by the same physician had a shorter mean interval (18.2 vs 88.3 days) than those assisted by different professionals (p = 0.015). The mean time for referral to our specialized center was 23 days., Conclusions: This study is a crucial step in recognizing barriers to early diagnosis of CNS tumors in a middle-income country as low awareness of signs/symptoms by parents and health professionals, aiming to provide opportunities for intervention strategies to reduce the time to diagnosis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aim: Early diagnosis and screening of breast cancer are of vital importance in the fight against the disease. It is crucial to identify the underlying barriers that prevent women from undergoing mammography and to develop necessary strategies to overcome these obstacles. The purpose of this study was to adapt "The Perceived Barriers of Mammography Scale (PBMS-23)" into Turkish and to conduct a validity and reliability study., Methods: This study used a methodological approach. The study was conducted with 233 women admitted to the Gynecology Outpatient Clinic of a university hospital. Data were collected by using the Introductory Information Form, PBMS-23, Champion's Health Belief Model Scale for Mammography Screening (CHBMS-MS). Psychometric properties of the scale were tested with content validity, confirmatory factor analysis, convergent validity, and test-retest reliability coefficient., Results: Content validity confirmatory factor analysis resulted in 𝜒 2 /SD = 1.67; CFI = 0.97, NFI = 0.92, GFI = 0.86, RMSEA = 0.054. The scale had a Cronbach's alpha of 0.87, while the subscales had Cronbach's alpha values of 0.34 to 0.80. The intraclass correlation coefficient values calculated for the test-retest reliability were between 0.83 and 0.96 for the subscales and 0.96 for the overall scale. There is a positive and statistically significant relationship (p < 0.01) between the CHBMS-MS barriers dimension and prejudices dimension scores and all subdimensions and the total of the PBMS-23., Conclusion: The PBMS-23 was accepted as a valid and reliable tool with 23 items and eight-factor structure that can be useful in measuring Turkish women's barriers to mammography., (© 2024 Japan Society of Obstetrics and Gynecology.)

Colorectal cancer (CRC) screening has been proven to reduce both mortality and the incidence of this disease. Most CRC screening programs are based on fecal immunochemical tests (FITs), which have a low participation rate. Searching for blood protein biomarkers can lead to the development of a more accepted screening test. The aim of this systematic review was to compare the diagnostic potential of the most promising serum protein biomarkers. A systematic review based on PRISMA guidelines was conducted in the PubMed and Web of Science databases between January 2010 and December 2023. Studies assessing blood protein biomarkers for CRC screening were included. The sensitivity, specificity, and area under the ROC curve of each biomarker were collected. Among 4685 screened studies, 94 were considered for analysis. Most of them were case-control studies, leading to an overestimation of the performance of candidate biomarkers. The performance of no protein biomarker or combination of biomarkers appears to match that of the FIT. Studies with a suitable design and population, testing new assay techniques, or based on algorithms combining FIT with serum tests are needed., (© 2024 The Author(s). Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Aim: Lung cancer is the most common cause of cancer death in Portugal. The Dutch-Belgian lung cancer screening (LCS) study (NELSON), the biggest European LCS study, showed a lung cancer mortality reduction in a high-risk population when being screened. In this study, the cost-effectiveness of LCS, based on the NELSON study protocol and outcomes, was evaluated compared with no screening in Portugal. Methods: The present study modified an established decision tree by incorporating a state-transition Markov model to evaluate the health-related advantages and economic implications of low-dose computed tomography (LDCT) LCS from the healthcare standpoint in Portugal. The analysis compared screening versus no screening for a high-risk population aged 50-75 with a smoking history. Various metrics, including clinical outcomes, costs, quality-adjusted life years (QALYs), life-years (LYs) and the incremental cost-effectiveness ratio (ICER), were calculated to measure the impact of LDCT LCS. Furthermore, scenario and sensitivity analyses were executed to assess the robustness of the obtained results. Results: Annual LCS with volume-based LDCT resulted in €558 million additional costs and 86,678 additional QALYs resulting in an ICER of €6440 per QALY for one screening group and a lifetime horizon. In total, 13,217 premature lung cancer deaths could be averted, leading to 1.41 additional QALYs gained per individual diagnosed with lung cancer. Results are robust based on the sensitivity analyses. Conclusion: This study showed that annual LDCT LCS for a high-risk population could be cost-effective in Portugal based on a willingness to pay a threshold of one-time the GDP (€19,290 per QALY gained).

Background: The Trans.IT database is a national gastrointestinal (GI) endoscopy database developed in 2012. It automatically collects anonymous data from GI endoscopy procedures in a centralized database. All endoscopists use a structured reporting tool for uniform data collection. In this study, we aim to provide an overview of the database and to evaluate its impact on data registration quality., Methods: We used all ERCPs, colonoscopies and colorectal cancer (CRC)-screening colonoscopies performed between 2016 and 2020. We excluded centers joining after 2016 and patients below age 18. Data registration quality for ERCPs included completeness of data for: intention of ERCP, Schutz score, ASA classification, papillary status (virgin or previous sphincterotomy), cannulation (success or failure to cannulate the desired duct) and procedural success. For colonoscopies: indication, ASA-classification, Boston Bowel Preparation Score (BBPS), cecal intubation, polyp detection rate (PDR). For CRC-screening colonoscopies, ASA-classification, BBPS, cecal intubation, PDR and adenoma detection rate (ADR)., Results: A total of 14,156 ERCPs, 150,962 colonoscopies and 37,199 colorectal cancer screening colonoscopies were included in our analysis. For ERCPs, registration of procedural intention, Schutz score, ASA classification, papillary status, cannulation and procedural success improved from 34.9%, 32.7%, 72.6%, 36.5%, 34.6%, 27.2% in 2016, to 86.4%, 84.6%, 97.4%, 86.4%, 82.1%, 84.0%, respectively, in 2020. For non-screening colonoscopies, registration of indication, ASA classification, BBPS, cecal intubation and PDR improved from 40.4%, 60.5%, 47.6%, 69.8% and 32.3% in 2016 to 90.3%, 88.9%, 59.8%, 79.1% and 39.1%, respectively, in 2020. For CRC-cancer screening colonoscopy registration equaled outcome, PDR and ADR changed from 74.7% to 63.6% in 2016 to 66.3% and 53.8% in 2020, respectively., Conclusions: The quality of endoscopy data registration has consistently improved over the years by using the Trans.IT database. This is most likely the result of feedback to performing endoscopists to review performance in real-time online and progressive awareness of quality of data registration., (© 2024 The Author(s). United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

The widespread implementation of low-dose computed tomography (LDCT) in lung cancer screening has led to the increasing detection of pulmonary nodules. However, precisely evaluating the malignancy risk of pulmonary nodules remains a formidable challenge. Here we propose a triage-driven Chinese Lung Nodules Reporting and Data System (C-Lung-RADS) utilizing a medical checkup cohort of 45,064 cases. The system was operated in a stepwise fashion, initially distinguishing low-, mid-, high- and extremely high-risk nodules based on their size and density. Subsequently, it progressively integrated imaging information, demographic characteristics and follow-up data to pinpoint suspicious malignant nodules and refine the risk scale. The multidimensional system achieved a state-of-the-art performance with an area under the curve (AUC) of 0.918 (95% confidence interval (CI) 0.918-0.919) on the internal testing dataset, outperforming the single-dimensional approach (AUC of 0.881, 95% CI 0.880-0.882). Moreover, C-Lung-RADS exhibited a superior sensitivity compared with Lung-RADS v2022 (87.1% versus 63.3%) in an independent cohort, which was screened using mobile computed tomography scanners to broaden screening accessibility in resource-constrained settings. With its foundation in precise risk stratification and tailored management, this system has minimized unnecessary invasive procedures for low-risk cases and recommended prompt intervention for extremely high-risk nodules to avert diagnostic delays. This approach has the potential to enhance the decision-making paradigm and facilitate a more efficient diagnosis of lung cancer during routine checkups as well as screening scenarios., Competing Interests: Competing interests F.S., Y.H., J.W. and Y.W. are employees of United Imaging Intelligence. The company had no involvement in the design, execution, surveillance, data analysis or interpretation of the study. The other authors have no competing interests., (© 2024. The Author(s).)

Background: The Pink Zone Pattern (PP) sign is a typical color alteration of early gastric cancer (EGC) under magnifying endoscopic narrow-band imaging (ME-NBI). By integrating the color changes (PP sign) with the "vessel plus surface (VS)" classification system, we developed an innovative diagnostic system for EGC and named it "Pink Microsurface Microvascular (PSV)" system. Here, we aimed to elucidate the diagnostic performance of the PSV system for EGC., Methods: We conducted a single-center prospective clinical study (before-after design) consisting of 2 cross-sectional studies at 2 separate periods. In the before phase, 184 suspected lesions were evaluated using the VS system under ME-NBI; in the after phase, 183 suspected lesions were evaluated using the PSV system. We compared the diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) between the VS group and the PSV group., Results: The accuracy, sensitivity, specificity, PPV, and NPV of the VS system for EGC were 84.6%, 87.0%, 83.6%, 67.8%, and 94.2%, respectively, and those for the PSV system were 93.0%, 92.0%, 93.4%, 85.2%, and 96.6%, respectively. The accuracy, specificity, and PPV of the PSV system were superior to those of the VS system. However, the sensitivity and NPV did not significantly differ between the VS system and the PSV system. The VS system was inconclusive for 22 lesions (12.0%) and the PSV system was inconclusive for 11 lesions (6.0%). The PSV system could identify more suspicious lesions than the VS system., Conclusions: We propose a new PSV diagnostic system by combining the VS system and the PP sign. Compared with the VS system, the PSV system could identify more suspected lesions and improve the diagnostic performance of EGC., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

To determine the preoperative detection of signet ring cancer cells (SRC) on upper endoscopy (EGD) in patients with CDH1 pathogenic variant (PV) undergoing gastrectomy. To evaluate the development of advanced diffuse gastric cancer (DGC) in patients choosing surveillance. Guidelines recommend prophylactic total gastrectomy (pTG) in CDH1 PV carriers with family history of DGC between 18 and 40 years. Annual EGD with biopsies according to established protocols is recommended in carriers with no SRC and no family history of DGC, with consideration of pTG. Retrospective analysis of asymptomatic patients with CDH1 PVs with ≥ 1 surveillance EGD. Outcomes included pre-operative EGD detection of SRC, surgical stage, and progression to advanced DGC in those electing surveillance with EGD. 48 patients with CDH1 PVs who had ≥ 1 EGD were included. 24/ 48 (50%) underwent gastrectomy, including pTG in 7 patients. SRCC were detected on gastrectomy specimen in 21/24 (87.5%). SRCs were identified by EGD in 17/21 patients who had SRCC on gastrectomy specimens (sensitivity 81%, 17/21). All cancers were stage pT1a. The remaining 17 patients (50% with a family history of gastric cancer) continue in annual EGD surveillance with a median follow-up of 34.6 months. No SRCC or advanced DGC have been diagnosed. No CDH1 PV carriers without SRCC on random biopsies followed in an endoscopic program developed advanced DGC over a median follow up of 3 years. In the short term, EGD surveillance might be a safe alternative to immediate pTG in experienced hands in referral centers., (© 2024. The Author(s).)

Objective: Cascade testing for hereditary cancer syndromes allows relatives to estimate cancer risk and pursue prevention and early detection strategies. The current paradigm relies on patient coordinated care, resulting in only one-third of relatives successfully completing testing. Studies suggest that team-based approaches, where clinicians facilitate testing, can increase uptake. As institutions consider implementing such programs, understanding patient characteristics associated with interest is crucial for resource allocation. We aim to assess interest in clinician-facilitated testing and evaluate barriers., Methods: Patients with cancer-associated pathogenic variants seen at a gynecologic oncology clinic were offered clinician-facilitated cascade testing. Patient interest and demographic variables were recorded and patients that declined were interviewed regarding the decision., Results: From 11/2023-4/2024, 139 patients were offered clinician-facilitated cascade testing. Median patient age was 43 years (IQR 17), 97 (69.8 %) self-identified as White and 101 (72.7 %) as non-Hispanic. Fifty-six (40.3 %) patients harbored a BRCA1 pathogenic variant, 37 (26.6 %) BRCA2, and 46 (33.1 %) other cancer-associated genes. Fifty-seven (41.0 %) patients expressed interest in the intervention. Interested patients were more likely to have been diagnosed in the prior year vs. patients who were not interested on univariate (OR 4.6, 95 % CI 2.0-10.2, P = 0.0002) and multivariable analyses (adjusted OR 3.8, 95 % CI 1.622-9.009, P = 0.0022)., Conclusions: Our study demonstrates that patients are almost five time more likely to be interested in cascade genetic testing within the first year of diagnosis of a pathogenic variant. Given the utility of such programs and their resource requirements, targeting this population could maximize effectiveness and uptake of cascade services., Competing Interests: Declaration of competing interest The authors have no financial or personal conflicts of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Organized cervical cancer (CxCa) screening is the most effective secondary prevention method to decrease the disease incidence and mortality. Screening for infection with 14 high-risk HPV genotypes (hrHPV) is recommended as primary screening test. Since only ca. 6 % of HPV-positive (HPV+) women will develop a high-grade lesion in 5 years, triage is critical for risk stratification and management of colposcopy resources. Dual staining (DS) p16/Ki67 cytology is an alternative to Papanicolau cytology (PAP) for triage of HPV+women, with potential improvements in sensitivity and specificity, and optimization of colposcopy referrals., Objectives: To compare PAP vs DS cytology in terms of (i) optimization of referrals for colposcopy and (ii) risk stratification to better define the follow-up interval., Study Design: Retrospective analysis of the CxCa screening database of Centro Hospitalar Universitário de Coimbra (CHUC), one of the centralized diagnostic laboratories for the CxCa screening program of the central region of Portugal, between July 2019 and May 2023. At CHUC, since July 2019, all samples from hrHPV+women have been triaged with liquid PAP and tested with DS cytology., Results: At baseline (1032 HPV+women), 1028 women were tested with DS: 739 women were DS negative (DS-) [70.7 % with normal PAP cytology (NILM) and 29.3 % with abnormal PAP cytology (ASC-US+)], and 289 were DS positive (DS+) (1.1 % NILM and 98.6 % ASC-US+). DS positivity as referral criterion for colposcopy instead of ASC-US+would have reduced the number of colposcopies by 39.4 % overall and by 48.3 % for other 12 hrHPV, while improving the number of colposcopies per HSIL (3.9 vs. 2.4 overall and 4.9 vs. 2.9 for other 12 hrHPV). In this cohort, if the follow-up interval for women positive for other 12 hrHPV+and DS- would have been extended from 1 to 3 years, 799 follow-up consultations, 799 HPV re-tests, and 277 colposcopies (-64.7 %) would have been avoided, with an overall risk of missed HSIL lesions of 2.2 %., Conclusions: Triage with DS allows the optimization of colposcopy referrals and a safe extension of the follow-up interval to 3 years for other 12 hrHPV+/DS- women, eliminating the need for annual re-testing for many women., Competing Interests: Declaration of competing interest The authors declare that the study has been conducted in accordance with the principles set forth in the Helsinki Declaration. BS, TR, FS, FA, and GF declare no conflicts of interest regarding the publication of this study. DO and CC are employees of Roche Diagnostics, Portugal. No funding to declare., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Lung cancer survival is significantly improved with early detection. However, lung cancer screening (LCS) uptake remains low despite national recommendations. Our aim was to determine whether implementation of an electronic medical record (EMR) alert and order set would increase LCS uptake., Study Design: A query of current and former smokers identified 62,630 patients aged 50 and above in the primary care setting between January 1, 2021 and May 5, 2022. We randomly reviewed 3704 charts for LCS eligibility and recorded who received LCS in the form of low-dose computed tomography amongst the eligible patients. We collected demographic information including gender, race, primary language, ethnicity, zip code, and insurance. Data analysis was performed utilizing 2-proportional z tests., Results: We identified 461 patients who were LCS eligible. Our overall LCS uptake was 19.9% (92/461). Three-time frames were analyzed: (1) prior to EMR alert implementation, (2) after implementation of EMR alert (January 7, 2021), and (3) after implementation of EMR alert and order set (March 3, 2021). Screening uptake was significantly improved with initiation of EMR alert (1/46 [2.2%] to 23/109 [21.1%]; P = .003). LCS uptake remained similarly high after subsequent order set implementation (23/109 [21.1%] and 68/306 [22.2%]; P = .72). Amongst the different demographics, age was significantly associated with screening uptake, with age ≥65 demonstrating statistically significant increased rates of screening (15.6% [41/263] for <65 vs 25.8% [51/198] for ≥65; P = .007)., Conclusion: Implementation of EMR alerts significantly improves LCS uptake in the primary care setting. Such efforts should be considered in other hospital settings to improve LCS uptake., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Timely detection of endometrial carcinoma in Lynch syndrome patients ensures prompt treatment and appropriate cancer screening for the patient and impacted family members. While cervical cytology is utilized primarily in cervical cancer screening, endometrial glandular abnormalities can be identified as part of routine cervical cancer screening or during work-up for abnormal uterine bleeding., Materials and Methods: We retrospectively evaluated cervical cytology samples from Lynch syndrome patients with endometrial carcinoma to determine how often atypical/malignant glandular cells were identified on prior/concurrent cytology., Results: We identified 14 Lynch syndrome patients with cervical cytology available within a year of endometrial carcinoma diagnosis. The average patient age was 55 years (36-73). Cervical cytology preceded diagnostic biopsy in 57% and was concurrent in 43%. A glandular abnormality was identified on original diagnosis in 43% and ranged from atypical glandular cells (AGC), not otherwise specified to adenocarcinoma consistent with endometrial primary. In 4 cases, abnormal cervical cytology triggered the subsequent biopsy. Evaluation of 8 cases with accessible cytology slides revealed 2 previously unrecognized glandular abnormalities, leading to an abnormal rate of 63% among cases reviewed retrospectively and a final glandular abnormality detection rate of 57% based on either original or review diagnosis., Conclusions: In summary, abnormal glandular cells were commonly identified in endometrial cancer patients with Lynch syndrome and led to endometrial cancer work-up and diagnosis in a subset. These results suggest that cervical cytology may have utility in endometrial cancer screening in this population and indicate that awareness of the patient's familial cancer risk is important for maximizing sensitivity of this test. They also caution against primary human papillomavirus screening in the Lynch syndrome population, as this may result in missed opportunities for early endometrial carcinoma detection among these high-risk individuals., (Copyright © 2024 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Cell-free DNA (cfDNA) analysis has shown potential in detecting early-stage lung cancer based on non-genetic features. To distinguish patients with lung cancer from healthy individuals, peripheral blood were collected from 926 lung cancer patients and 611 healthy individuals followed by cfDNA extraction. Low-pass whole genome sequencing and targeted methylation sequencing were conducted and various features of cfDNA were evaluated. With our customized algorithm using the most optimal features, the ensemble stacked model was constructed, called ESim-seq (Early Screening tech with Integrated Model). In the independent validation cohort, the ESim-seq model achieved an area under the curve (AUC) of 0.948 (95 % CI: 0.915-0.981), with a sensitivity of 79.3 % (95 % CI: 71.5-87.0 %) across all stages at a specificity of 96.0 % (95 % CI: 90.6-100.0 %). Specifically, the sensitivity of the ESim-seq model was 76.5 % (95 % CI: 67.3-85.8 %) in stage I patients, 100 % (95 % CI: 100.0-100.0 %) in stage II patients, 100 % (95 % CI: 100.0-100.0 %) in stage III patients and 87.5 % (95 % CI: 64.6%-100.0 %) in stage IV patients in the independent validation cohort. Besides, we constructed LCSC model (Lung Cancer Subtype multiple Classification), which was able to accurately distinguish patients with small cell lung cancer from those with non-small cell lung cancer, achieving an AUC of 0.961 (95 % CI: 0.949-0.957). The present study has established a framework for assessing cfDNA features and demonstrated the benefits of integrating multiple features for early detection of lung cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Mammography screening supported by deep learning-based artificial intelligence (AI) solutions can potentially reduce workload without compromising breast cancer detection accuracy, but the site of deployment in the workflow might be crucial. This retrospective study compared three simulated AI-integrated screening scenarios with standard double reading with arbitration in a sample of 249 402 mammograms from a representative screening population. A commercial AI system replaced the first reader (scenario 1: integrated AI first ), the second reader (scenario 2: integrated AI second ), or both readers for triaging of low- and high-risk cases (scenario 3: integrated AI triage ). AI threshold values were chosen based partly on previous validation and setting the screen-read volume reduction at approximately 50% across scenarios. Detection accuracy measures were calculated. Compared with standard double reading, integrated AI first showed no evidence of a difference in accuracy metrics except for a higher arbitration rate (+0.99%, P < .001). Integrated AI second had lower sensitivity (-1.58%, P < .001), negative predictive value (NPV) (-0.01%, P < .001), and recall rate (-0.06%, P = .04) but a higher positive predictive value (PPV) (+0.03%, P < .001) and arbitration rate (+1.22%, P < .001). Integrated AI triage achieved higher sensitivity (+1.33%, P < .001), PPV (+0.36%, P = .03), and NPV (+0.01%, P < .001) but lower arbitration rate (-0.88%, P < .001). Replacing one or both readers with AI seems feasible; however, the site of application in the workflow can have clinically relevant effects on accuracy and workload. Keywords: Mammography, Breast, Neoplasms-Primary, Screening, Epidemiology, Diagnosis, Convolutional Neural Network (CNN) Supplemental material is available for this article. Published under a CC BY 4.0 license.

Oral exfoliative cytology has emerged as a valuable tool in the early detection of oral cancer and other systemic diseases. This review comprehensively examines the current applications and recent advancements in oral exfoliative cytology techniques. We analyzed published literature from the past decade, focusing on methodological improvements, diagnostic accuracy, and emerging applications. Key findings include: (1) Enhanced cell collection and preparation methods have significantly improved sample quality and diagnostic reliability. (2) Integration of molecular markers and DNA analysis with traditional cytomorphological assessment has increased diagnostic sensitivity and specificity for oral cancer detection. (3) Novel applications in systemic disease detection, including diabetes and iron overload disorders, demonstrate the expanding utility of this technique. (4) Computer-assisted analysis and deep learning algorithms show promise in improving diagnostic accuracy and efficiency. Despite these advancements, challenges remain in standardization and widespread clinical implementation. This review provides a critical evaluation of oral exfoliative cytology's current status and future potential in oral and systemic disease diagnosis., (© 2024 Wiley Periodicals LLC.)

Pleural mesothelioma is a rare and aggressive cancer that affects the pleura. In recent years, there has been increasing interest and attention in detecting and diagnosing early-stage or precancerous forms of mesothelioma because of its severe prognosis and short life expectancy at the time of diagnosis. Mesothelioma in situ represents a clear opportunity to improve and innovate the diagnostic approach and the multimodality treatment of mesothelioma: the diagnosis of pleural mesothelioma at the 'in-situ phase' means early disease detection and thus paves the way to new possible curable strategies. Since 2021, when mesothelioma in situ was finally identified and described as a new histological entity, its diagnosis and management became a challenge and the subject of ongoing research; several aspects remain open and still outstanding as regards diagnostic techniques, time and probability of progression, need for and methods of follow up, aggressive and early surgery. This narrative review aims to provide a comprehensive overview of mesothelioma in situ covering its definition, risk factors, diagnostic criteria, and tricky aspects of early detection. It also highlights its clinical significance, new perspectives, and potential future indications in the context of pleural mesothelioma multidisciplinary management., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide. Accurate cancer risk assessment approaches could increase rates of early CRC diagnosis, improve health outcomes for patients and reduce pressure on diagnostic services. The faecal immunochemical test (FIT) for blood in stool is widely used in primary care to identify symptomatic patients with likely CRC. However, there is a 6-16% noncompliance rate with FIT in clinic and ~90% of patients over the symptomatic 10 µg/g test threshold do not have CRC. A polygenic risk score (PRS) quantifies an individual's genetic risk of a condition based on many common variants. Existing PRS for CRC have so far been used to stratify asymptomatic populations. We conducted a retrospective cohort study of 50,387 UK Biobank participants with a CRC symptom in their primary care record at age 40+. A PRS based on 201 variants, 5 genetic principal components and 22 other risk factors and markers for CRC were assessed for association with CRC diagnosis within 2 years of first symptom presentation using logistic regression. Associated variables were included in an integrated risk model and trained in 80% of the cohort to predict CRC diagnosis within 2 years. An integrated risk model combining PRS, age, sex, and patient-reported symptoms was predictive of CRC development in a testing cohort (receiver operating characteristic area under the curve, ROCAUC: 0.76, 95% confidence interval: 0.71-0.81). This model has the potential to improve early diagnosis of CRC, particularly in cases of patient noncompliance with FIT., Competing Interests: Competing interests The authors declare no competing interests. Ethical approval Data from the UK Biobank Resource were accessed under Application Number 74981. UK Biobank was approved as tissue bank resource by North West Multi-centre Research Ethics Committee. All UK Biobank participants gave written informed consent for use of their data for health research. Participants who withdrew consent during this study were excluded from analysis., (© 2024. The Author(s).)

Although the fecal immunochemical test for hemoglobin (FIT) is a widely used screening test for colorectal cancer, it is not sensitive enough to detect advanced colorectal adenoma. To address this issue, we performed this study to investigate whether combining the FIT and fecal DNA testing of methylated somatostatin (SST) could improve diagnostic performance for advanced colorectal adenoma. We collected feces from 79 healthy subjects with negative results on colonoscopy, 43 patients with non-advanced colorectal adenoma, 117 patients with advanced colorectal adenoma, and 126 patients with colorectal cancer. After fecal DNA was incubated with methylation-sensitive restriction enzymes, SST methylation levels were measured by droplet digital PCR. Using logistic multivariate analysis, we established a prediction formula for detecting colorectal neoplasia and named it the FAMS (FIT, age, methylated SST) index. The diagnostic performance of a single use of FIT for advanced colorectal adenoma showed a sensitivity of 29.1% (34/117) and specificity of 89.3% (109/122). In contrast, the FAMS index showed a sensitivity of 56.4% (66/117) at a similar specificity point of 91.0% (111/122). Furthermore, even at the higher specificity point of 94.3% (115/122), the sensitivity was still higher than that of FIT, reaching 42.7% (50/117). As the FAMS index showed better diagnostic performance for advanced colorectal adenoma than a single use of FIT, the FAMS index could be a promising tool for detecting advanced colorectal adenoma., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: Surveillance colonoscopy after polyps have been detected at screening aims to reduce the risk for subsequent colorectal cancer, so-called post-colonoscopy colorectal cancer (PCCRC). Inconsistencies exist as to whether the risk should be stratified by histologic subtype. We aimed to compare the risk for PCCRC mortality in screening participants with sessile serrated lesions (SSLs)/traditional serrated adenomas (TSAs), hyperplastic polyps (HPPs), or conventional adenomas., Methods: Screening colonoscopy registry data were linked to death registry data between 2010 and 2022. We assessed the association of PCCRC death after a diagnosis of SSL/TSA, conventional adenoma, or HPP by Cox regression, and stratified by polyp size ≥10 and <10 mm., Results: 383,801 participants were included in the analysis. There were 1490 HPPs ≥10 mm (2.6%), compared with 1853 SSL/TSAs (19.6%) and 10,960 conventional adenomas (12.9%). When adjusted for polyp location, the association of polyp size ≥10 mm with PCCRC death was of similar magnitude in participants with conventional adenomas (hazard ratio [HR] 3.68, 95%CI 2.49-5.44), SSL/TSAs (HR 2.55, 95%CI 1.13-5.72), and HPPs (HR 5.01, 95%CI 2.45-10.22). Participants with HPPs mostly died of tumors in the distal colon (54.1%; n = 20), while participants with SSL/TSAs more frequently died of proximal tumors (33.3%; n = 3)., Conclusions: Across all histologic types, participants with polyps ≥10 mm had at least a two-fold increase in the likelihood of PCCRC death compared with those with polyps <10 mm. These data suggest that size, rather than histologic subtype, should be a determinant for risk stratification after screening colonoscopy., Competing Interests: M. Trauner has been an advisor for Abbvie, Albireo, BiomX, Boehringer Ingelheim, Falk, Gilead, Genfit, Hightide, Intercept, Jannsen, MSD, Novartis, Phenex, Pliant, Regulus, Siemens, and Shire; has received speaker's fees from BMS, Falk Foundation, Gilead, Intercept, MSD, and Roche; travel grants from AbbVie, Falk Foundation, Gilead, Intercept, Janssen, and Roche; and grants/research support from Albireo, Alnylam, Cymabay, Falk Pharma, Gilead, Intercept, MSD, Madrigal, Takeda, and UltraGenyx. The Medical Universities of Graz and Vienna have filed patents on medical use of norUDCA and M. Trauner is listed as a co-inventor. J. Zessner-Spitzenberg, E. Waldmann, L.-M. Rockenbauer, A. Demschik, D. Penz, and M. Ferlitsch declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background and Aims: Lymph node metastasis significantly affects the prognosis of early gastric cancer patients. EUS plays a crucial role in the preoperative assessment of early gastric cancer. This study evaluated the efficacy of EUS in identifying lymph node metastasis in early gastric cancer patients and developed a risk score model to aid in choosing the best treatment options., Methods: We retrospectively analyzed the effectiveness of EUS for detecting lymph node metastasis in early gastric cancer patients. A risk score model for predicting lymph node metastasis preoperatively was created using independent risk factors identified through binary logistic regression analysis and subsequently validated. Receiver operating characteristic curves were generated for both the development and validation cohorts., Results: The overall accuracy of EUS in identifying lymph node metastasis was 85.3%, although its sensitivity (29.2%) and positive predictive value (38.7%) were relatively low. Patients were categorized based on preoperative risk factors for lymph node metastasis, including tumor size of ≥20 mm, lymph nodes of ≥10 mm, body mass index of ≥24 kg/m 2 , and lymph node metastasis on CT scans. A 7-point risk score model was developed to assess the likelihood of lymph node metastasis. The areas under the receiver operating characteristic curve for the development and validation sets were 0.842 and 0.837, respectively, with sensitivities of 64% and 79%, respectively., Conclusions: We developed a practical risk score model based on preoperative factors to help EUS predict lymph node metastasis in early gastric cancer patients, guiding the selection of optimal treatment approaches for these patients., Competing Interests: Disclosure All authors disclosed no financial relationships. This study was supported by grants from the distinguished professor of Tianjin (Jiaowu Tianjin Zhengwu Ban [2019] no. 120), National Key Research and Development Program “precision medicine research” (2017YFC0908304), National Key Research and Development Program “major chronic noninfectious disease research” (2016YFC1303202), and the Programs of National Natural Science Foundation of China (no. 81572372)., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Introduction: Cervical cytology remains a critical screening tool for cervical cancer. While various factors can influence cytology quality, the effect of lubricant type used during specimen collection has been previously studied with inconclusive results. This study aimed to evaluate the impact of surgical lubricant on cervical cytology results and elucidate risk factors associated with unsatisfactory results. We hypothesized that switching from a carbomer-containing lubricant to a noncarbomer, water-soluble lubricant would improve specimen adequacy in cervical cytology., Materials and Methods: A retrospective chart review was performed examining patient cytologic results from January to December 2017 at a single academic institution. After historical rates of unsatisfactory cytology were higher than acceptable standards, the practice changed lubricant formulation from a carbomer containing lubricant to a noncarbomer, water soluble lubricant. Demographic data and treatment characteristics were collected for eligible patients. Matched analysis was performed to examine factors associated with an unsatisfactory cytology result., Results: After the change in lubricant, there was a significant decline in the rates of unsatisfactory cytology from 9.6% to 5.7%, P = 0.01. This decline was also observed when patients were matched based on menopausal status, personal history of gynecologic malignancy, pregnancy status, and cytology specimen type (10.0% to 4.8%, P = 0.001)., Conclusions: Change in lubricant from a carbomer containing to noncarbomer, water soluble product was associated with a statistically significant decline in the rates of unsatisfactory cytology. Although prior data have had mixed results as to the etiology of unsatisfactory cytology, we feel that this directly contributed to the high rates observed at our institution., (Copyright © 2024 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Purpose: Our goal was to quantify the ability of various PSA values in predicting the likelihood of developing metastatic or fatal prostate cancer in older men., Materials and Methods: We used a random sample of patients in the US Veterans Health Administration to identify 80,706 men who had received PSA testing between ages 70 to 75. Our primary end point was time to development of either metastatic prostate cancer or death from prostate cancer. We used cumulative/dynamic modeling to account for competing events (death from non-prostate cancer causes) in studying both the discriminative ability of PSA as well as for positive predictive value and negative predictive value at 3 time points., Results: PSA demonstrated time-dependent predictive discrimination, with receiver operating characteristic area under the curve at 5, 10, and 14 years decreasing from 0.83 to 0.77 to 0.73, respectively, but without statistically significant difference when stratified by race. At PSA thresholds between 1 and 8 ng/mL, the positive predictive value of developing advanced prostate cancer was significantly greater in Black than White patients. For instance, at a PSA > 3, at 5, 10, and 14 years, White patients had 2.4%, 2.9%, and 3.7% risk of an event, whereas Black patients had 4.3%, 6.5%, and 8.3% risk., Conclusions: In men aged 70 to 75 deciding whether to cease PSA testing with borderline-elevated PSA values, the risk of developing metastatic or fatal prostate cancer is quantifiable and relatively low. Risk assessment in this setting must account for the higher incidence of prostate cancer in Black men.

In the rapidly evolving field of medical diagnostics, biomarkers play a pivotal role, particularly in the early detection of cancer. Cluster of differentiation 5 (CD5), a cell surface glycoprotein found on T cells and B-1a lymphocytes, is instrumental in immune regulation and is associated with both autoimmune diseases and malignancies. Despite its significant diagnostic and therapeutic potential, CD5 detection has been limited by modern methods in the pg/ml range. This study presents a novel multimodal electrochemical immunosensor that employs laser-processed Ti/Au electrodes for the ultra-sensitive detection of CD5 in human blood serum. The "multimodal" approach combines different analytical techniques - differential pulse volctammetry (DPV) and electrochemical impedance spectroscopy (EIS) - to ensure comprehensive analysis, enhancing both the accuracy and reliability of the sensor. This novel sensor significantly outperforms existing commercial ELISA kits, achieving a limit of detection (LOD) of 1.1 ± 0.2 fg/mL with DPV and 3.9 ± 0.5 fg/mL with EIS in phosphate-buffered saline (PBS) and 6.6 ± 3.1 fg/mL and 15.6 ± 3.1 fg/mL in human serum (HS), respectively. These results highlight the immunosensor's potential for improving early-stage cancer diagnosis and broader medical applications., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Igor Iatsunskyi reports financial support was provided by Adam Mickiewicz University. Igor Iatsunskyi reports a relationship with Adam Mickiewicz University that includes: employment., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: We present findings from an assessment of award recipients' partners from the Centers for Disease Control and Prevention's Colorectal Cancer Control Program (CRCCP). We describe partners' processes of identifying and tracking patients undergoing stool-based screening., Methods: We analyzed data from eight CRCCP award recipients purposively sampled and their partner health systems from 2019 to 2023. The data included number of stool-based tests distributed and returned; abnormal findings; referrals and completion of follow-up colonoscopies; and colonoscopy findings. We also report on strategies to improve tracking of stool-based tests and facilitation of follow-up colonoscopies., Results: Five of eight CRCCP award recipients reported that all or some partner health systems were able to report stool test return rates. Six had health systems that were able to report abnormal stool test findings. Two reported that health systems could track time to follow-up colonoscopy completion from date of referral, while four could report colonoscopy completion but not the timeframe. Follow-up colonoscopy completion varied substantially from 24.2 to 75.5% (average of 47.9%). Strategies to improve identifying and tracking screening focused mainly on the use of electronic medical records; strategies to facilitate follow-up colonoscopy were multi-level., Conclusion: Health systems vary in their ability to track steps in the stool-based screening process and few health systems can track time to completion of follow-up colonoscopy. Longer time intervals can result in more advanced disease. CRCCP-associated health systems participating in this study could support the implementation of multicomponent strategies at the individual, provider, and health system levels to improve tracking and completion of follow-up colonoscopy., Competing Interests: Declarations Competing interests The authors declare no competing interests. Conflict of interests The authors have no relevant financial or non-financial interests to disclose. Ethics approval Institutional Review Board approval was not required because it was determined this study was not research involving human subjects. Consent to participate Not applicable. Consent to publish Not applicable., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)