Stool Glycoproteomics Signatures of Pre-Cancerous Lesions and Colorectal Cancer.

Colorectal cancer (CRC) screening relies primarily on stool analysis to identify occult blood. However, its sensitivity for detecting precancerous lesions is limited, requiring the development of new tools to improve CRC screening. Carcinogenesis involves significant alterations in mucosal epithelium glycocalyx that decisively contribute to disease progression. Building on this knowledge, we examined patient series comprehending premalignant lesions, colorectal tumors, and healthy controls for the T-antigen-a short-chain O-glycosylation of proteins considered a surrogate marker of malignancy in multiple solid cancers. We found the T-antigen in the secretions of dysplastic lesions as well as in cancer. In CRC, T-antigen expression was associated with the presence of distant metastases. In parallel, we analyzed a broad number of stools from individuals who underwent colonoscopy, which showed high T expressions in high-grade dysplasia and carcinomas. Employing mass spectrometry-based lectin-affinity enrichment, we identified a total of 262 proteins, 67% of which potentially exhibited altered glycosylation patterns associated with cancer and advanced pre-cancerous lesions. Also, we found that the stool (glyco)proteome of pre-cancerous lesions is enriched for protein species involved in key biological processes linked to humoral and innate immune responses. This study offers a thorough analysis of the stool glycoproteome, laying the groundwork for harnessing glycosylation alterations to improve non-invasive cancer detection.

Colorectal Cancer Diagnosis through Breath Test Using a Portable Breath Analyzer-Preliminary Data.

Screening methods available for colorectal cancer (CRC) to date are burdened by poor reliability and low patient adherence and compliance. An altered pattern of volatile organic compounds (VOCs) in exhaled breath has been proposed as a non-invasive potential diagnostic tool for distinguishing CRC patients from healthy controls (HC). The aim of this study was to evaluate the reliability of an innovative portable device containing a micro-gas chromatograph in enabling rapid, on-site CRC diagnosis through analysis of patients' exhaled breath. In this prospective trial, breath samples were collected in a tertiary referral center of colorectal surgery, and analysis of the chromatograms was performed by the Biomedical Engineering Department. The breath of patients with CRC and HC was collected into Tedlar bags through a Nafion filter and mouthpiece with a one-way valve. The breath samples were analyzed by an automated portable gas chromatography device. Relevant volatile biomarkers and discriminant chromatographic peaks were identified through machine learning, linear discriminant analysis and principal component analysis. A total of 68 subjects, 36 patients affected by histologically proven CRC with no evidence of metastases and 32 HC with negative colonoscopies, were enrolled. After testing a training set (18 CRC and 18 HC) and a testing set (18 CRC and 14 HC), an overall specificity of 87.5%, sensitivity of 94.4% and accuracy of 91.2% in identifying CRC patients was found based on three VOCs. Breath biopsy may represent a promising non-invasive method of discriminating CRC patients from HC.

The role of galanin in the progression and prognosis of colorectal cancer: the unfinished story.

The paper presents a summary of immunohistochemical (IHC) and biochemical investigations on the presence of galanin (Gal), one of the neuropeptides abundant in the enteric nervous systems, and three types of its receptors (GalR1-3) in colorectal cancer (CRC) tissue and non-involved colon wall and their associations with clinical-pathological data of the CRC patients. We were the first to morphologically demonstrate the presence of endogenous Gal in CRC sections and measure its content in homogenates of tumor tissue and dissected compartments of unchanged colon wall. The prominent atrophy of myenteric plexuses displaying Gal immunoreactivity (Gal-Ir) located close to the tumor invasion was found to be accompanied by higher Gal content in the tumor-adjacent muscularis externa than in tumor-distant tissue. In further studies for the first time, we demonstrated by the IHC technique the presence of the GalR1-3 receptors in the CRC tumors and the colon mucosa and found that higher GalR3-Ir in the tumor tissue correlated with longer overall survival of CRC patients. Furthermore, we discovered that lower GalR1 expression in submucosal plexuses located near the tumor correlated with a better prognosis in patients with CRC. These findings suggest that GalR1 could be considered as a novel therapeutic target in CRC. In conclusion, our morphological investigations provided novel data documenting the involvement of Gal and its receptors in the progression of CRC and showed the usefulness of the IHC technique for the prognosis of CRC patients.

Screening for Colorectal Cancer.

Colorectal cancer (CRC) is the second leading cause of cancer death. Screening has been proven to reduce both cancer incidence and cancer-related mortality. Various screening tests are available, each with their own advantages and disadvantages and varying levels of evidence to support their use. Clinicians should offer CRC screening to average-risk persons aged 50 to 75 years; starting screening at age 45 years remains controversial. Screening may be beneficial in select persons aged 76 to 85 years, based on their overall health and screening history. Offering a choice of screening tests or sequentially offering an alternate test for those who do not complete screening can significantly increase participation.

COVID-related disruptions to colorectal cancer screening, diagnosis, and treatment could increase cancer Burden in Australia and Canada: A modelling study.

COVID-19 disrupted cancer control worldwide, impacting preventative screening, diagnoses, and treatment services. This modelling study estimates the impact of disruptions on colorectal cancer cases and deaths in Canada and Australia, informed by data on screening, diagnosis, and treatment procedures. Modelling was used to estimate short- and long-term effects on colorectal cancer incidence and mortality, including ongoing impact of patient backlogs. A hypothetical mitigation strategy was simulated, with diagnostic and treatment capacities increased by 5% from 2022 to address backlogs. Colorectal cancer screening dropped by 40% in Canada and 6.3% in Australia in 2020. Significant decreases to diagnostic and treatment procedures were also observed in Australia and Canada, which were estimated to lead to additional patient wait times. These changes would lead to an estimated increase of 255 colorectal cancer cases and 1,820 colorectal cancer deaths in Canada and 234 cases and 1,186 deaths in Australia over 2020-2030; a 1.9% and 2.4% increase in mortality, respectively, vs a scenario with no screening disruption or diagnostic/treatment delays. Diagnostic and treatment capacity mitigation would avert 789 and 350 deaths in Canada and Australia, respectively. COVID-related disruptions had a significant impact on colorectal cancer screening, diagnostic, and treatment procedures in Canada and Australia. Modelling demonstrates that downstream effects on disease burden could be substantial. However, backlogs can be managed and deaths averted with even small increases to diagnostic and treatment capacity. Careful management of resources can improve patient outcomes after any temporary disruption, and these results can inform targeted approaches early detection of cancers.

The implementation and mechanisms of advance notification for cancer screening: A scoping review.

OBJECTIVE: To describe and synthesise information on the content and delivery of advance notifications (information about cancer screening delivered prior to invitation) used to increase cancer screening participation and to understand the mechanisms that may underlie their effectiveness. METHODS: Searches related to advance notification and cancer screening were conducted in six electronic databases (APA PsycINFO, CINAHL, Cochrane Library, Embase, PubMed, Web of Science) and results were screened for eligibility. Study characteristics, features of the advance notifications (cancer type, format, delivery time, and content), and the effect of the notifications on cancer screening participation were extracted. Features were summarised and compared across effective versus ineffective notifications. RESULTS: Thirty-two articles were included in this review, reporting on 33 unique advance notifications. Of these, 79% were sent via postal mail, 79% were distributed prior to bowel cancer screening, and most were sent 2 weeks before the screening offer. Twenty-two full versions of the advance notifications were obtained for content analysis. Notifications included information about cancer risk, the benefits of screening, barriers to participation, social endorsement of cancer screening, and what to expect throughout the screening process. Of the 19 notifications whose effect was tested statistically, 68% were found to increase screening (by 0.7%-16%). Effectiveness did not differ according to the format, delivery time, or content within the notification, although some differences in cancer type were observed. CONCLUSION: Future research should explore the effectiveness of advance notification via alternative formats and for other screening contexts and disentangle the intervention- and person-level factors driving its effect on screening participation.

The impact of surgical volume on outcomes in newly diagnosed colorectal cancer patients receiving definitive surgeries.

Colorectal cancer (CRC) patients who receive cancer surgeries from higher-volume providers may have better outcomes. However, the definitions of surgical volume may affect the results. We aim to analyze the effects of different definitions of surgical volume on patient outcomes. We conducted a nationwide population-based study in Taiwan that enrolled all patients who underwent definitive surgery for newly diagnosed CRC. We used three common definitions of surgical volume: total volume means the total surgical number conducted by the same provider during the study period; cumulative volume was calculated as the number of operations the surgeon performed before the index procedure; annual volume was calculated as the number of times the surgeon had been responsible for surgery during the index year. In this study, we included 100,009 newly diagnosed CRC patients, including 55.8% males, of median age 66 years at diagnosis (range 20-105 years). After adjustment for the patient and provider characteristics, we found that CRC patients receiving definitive surgery by higher-volume providers had better outcomes, especially where surgeon volume may play a more important role than hospital volume. The cumulative volume could predict the 5-year mortality of the study cohort better than the total and annual volume.

The impact of the affordable care act and Medicaid expansion on colorectal cancer screening: Evidence from the 5th year of Medicaid expansion.

BACKGROUND: Colorectal cancer screening rates remain suboptimal, particularly among low-income populations. Our objective was to evaluate the long-term effects of Medicaid expansion on colorectal cancer screening. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study analyzed data from 354,384 individuals aged 50-64 with an income below 400% of the federal poverty level (FPL), who participated in the Behavioral Risk Factors Surveillance System from 2010 to 2018. A difference-in-difference analysis was employed to estimate the effect of Medicaid expansion on colorectal cancer screening. Subgroup analyses were conducted for individuals with income up to 138% of the FPL and those with income between 139% and 400% of the FPL. The effect of Medicaid expansion on colorectal cancer screening was examined during the early, mid, and late expansion periods. MAIN OUTCOMES AND MEASURES: The primary outcome was the likelihood of receiving colorectal cancer screening for low-income adults aged 50-64. RESULTS: Medicaid expansion was associated with a significant 1.7 percentage point increase in colorectal cancer screening rates among adults aged 50-64 with income below 400% of the FPL (p < 0.05). A significant 2.9 percentage point increase in colorectal cancer screening was observed for those with income up to 138% the FPL (p < 0.05), while a 1.5 percentage point increase occurred for individuals with income between 139% and 400% of the FPL. The impact of Medicaid expansion on colorectal cancer screening varied based on income levels and displayed a time lag for newly eligible beneficiaries. CONCLUSIONS: Medicaid expansion was found to be associated with increased colorectal cancer screening rates among low-income individuals aged 50-64. The observed variations in impact based on income levels and the time lag for newly eligible beneficiaries receiving colorectal cancer screening highlight the need for further research and precision public health strategies to maximize the benefits of Medicaid expansion on colorectal cancer screening rates.

Stage at diagnosis of colorectal cancer through diagnostic route: Who should be screened?

BACKGROUND: Colorectal cancer (CRC) is a global health concern, with advanced-stage diagnoses contributing to poor prognoses. The efficacy of CRC screening has been well-established; nevertheless, a significant proportion of patients remain unscreened, with > 70% of cases diagnosed outside screening. Although identifying specific subgroups for whom CRC screening should be particularly recommended is crucial owing to limited resources, the association between the diagnostic routes and identification of these subgroups has been less appreciated. In the Japanese cancer registry, the diagnostic routes for groups discovered outside of screening are primarily categorized into those with comorbidities found during hospital visits and those with CRC-related symptoms. AIM: To clarify the stage at CRC diagnosis based on diagnostic routes. METHODS: We conducted a retrospective observational study using a cancer registry of patients with CRC between January 2016 and December 2019 at two hospitals. The diagnostic routes were primarily classified into three groups: Cancer screening, follow-up, and symptomatic. The early-stage was defined as Stages 0 or I. Multivariate and univariate logistic regressions were exploited to determine the odds of early-stage diagnosis in the symptomatic and cancer screening groups, referencing the follow-up group. The adjusted covariates were age, sex, and tumor location. RESULTS: Of the 2083 patients, 715 (34.4%), 1064 (51.1%), and 304 (14.6%) belonged to the follow-up, symptomatic, and cancer screening groups, respectively. Among the 2083 patients, CRCs diagnosed at an early stage were 57.3% (410 of 715), 23.9% (254 of 1064), and 59.5% (181 of 304) in the follow-up, symptomatic, and cancer screening groups, respectively. The symptomatic group exhibited a lower likelihood of early-stage diagnosis than the follow-up group [P < 0.001, adjusted odds ratio (aOR), 0.23; 95% confidence interval (95%CI): 0.19-0.29]. The likelihood of diagnosis at an early stage was similar between the follow-up and cancer screening groups (P = 0.493, aOR for early-stage diagnosis in the cancer screening group vs follow-up group = 1.11; 95%CI = 0.82-1.49). CONCLUSION: CRCs detected during hospital visits for comorbidities were diagnosed earlier, similar to cancer screening. CRC screening should be recommended, particularly for patients without periodical hospital visits for comorbidities.

Investigation of long non-coding RNAs in extracellular vesicles from low-volume blood serum specimens of colorectal cancer patients.

Colorectal cancer (CRC) is the second most prevalent cancer type worldwide, which highlights the urgent need for non-invasive biomarkers for its early detection and improved prognosis. We aimed to investigate the patterns of long non-coding RNAs (lncRNAs) in small extracellular vesicles (sEVs) collected from low-volume blood serum specimens of CRC patients, focusing on their potential as diagnostic biomarkers. Our research comprised two phases: an initial exploratory phase involving RNA sequencing of sEVs from 76 CRC patients and 29 healthy controls, and a subsequent validation phase with a larger cohort of 159 CRC patients and 138 healthy controls. Techniques such as dynamic light scattering, transmission electron microscopy, and Western blotting were utilized for sEV characterization. Optimized protocol for sEV purification, RNA isolation and preamplification was applied to successfully sequence the RNA content of sEVs and validate the results by RT-qPCR. We successfully isolated sEVs from blood serum and prepared sequencing libraries from a low amount of RNA. High-throughput sequencing identified differential levels of 460 transcripts between CRC patients and healthy controls, including mRNAs, lncRNAs, and pseudogenes, with approximately 20% being lncRNAs, highlighting several tumor-specific lncRNAs that have not been associated with CRC development and progression. The validation phase confirmed the upregulation of three lncRNAs (NALT1, AL096828, and LINC01637) in blood serum of CRC patients. This study not only identified lncRNA profiles in a population of sEVs from low-volume blood serum specimens of CRC patients but also highlights the value of innovative techniques in biomolecular research, particularly for the detection and analysis of low-abundance biomolecules in clinical samples. The identification of specific lncRNAs associated with CRC provides a foundation for future research into their functional roles in cancer development and potential clinical applications.

Willingness of healthcare providers to perform population-based cancer screening: a cross-sectional study in primary healthcare institutions in Tianjin, China.

OBJECTIVE: To evaluate the willingness of healthcare providers to perform population-based screening in primary healthcare institutions in China. METHODS: Healthcare providers of 262 primary healthcare institutions in Tianjin were invited to fill out a questionnaire consisting of demographic characteristics, workload, and knowledge of, attitude towards and willingness to perform breast, cervical and colorectal cancer screening. Willingness to screen was the primary outcome. Multilevel logistic regression models were conducted to analyse the determinants of healthcare providers' willingness to screen. ORs and 95% CIs were estimated. RESULTS: A total of 554 healthcare providers from 244 institutions answered the questionnaire. 67.2%, 72.1% and 74.3% were willing to perform breast, cervical and colorectal cancer screening, respectively. A negative attitude towards screening was associated with a low willingness for cervical (OR=0.27; 95% CI 0.08, 0.94) and colorectal (OR=0.08; 95% CI 0.02, 0.30) cancer screening, while this was not statistically significant for breast cancer screening (OR=0.30; 95% CI 0.08, 1.12). For breast, cervical and colorectal cancer screening, 70.1%, 63.8% and 59.0% of healthcare providers reported a shortage of staff dedicated to screening. A perceived reasonable manpower allocation was a determinant of increased willingness to perform breast (OR=2.86; 95% CI 1.03, 7.88) and colorectal (OR=2.70; 95% CI 1.22, 5.99) cancer screening. However, this was not significant for cervical cancer screening (OR=1.76; 95% CI 0.74, 4.18). CONCLUSIONS: In China, healthcare providers with a positive attitude towards screening have a stronger willingness to contribute to cancer screening, and therefore healthcare providers' attitude, recognition of the importance of screening and acceptable workload should be optimised to improve the uptake of cancer screening.

Study protocol for a mixed methods approach to optimize colorectal cancer screening in Malaysia: Integrating stakeholders insights and knowledge-to-action framework.

INTRODUCTION: Colorectal cancer is a growing global health concern and the number of reported cases has increased over the years. Early detection through screening is critical to improve outcomes for patients with colorectal cancer. In Malaysia, there is an urgent need to optimize the colorectal cancer screening program as uptake is limited by multiple challenges. This study aims to systematically identify and address gaps in screening service delivery to optimize the Malaysian colorectal cancer screening program. METHODS: This study uses a mixed methods design. It focuses primarily on qualitative data to understand processes and strategies and to identify specific areas that can be improved through stakeholder engagement in the screening program. Quantitative data play a dual role in supporting the selection of participants for the qualitative study based on program monitoring data and assessing inequalities in screening and program implementation in healthcare facilities in Malaysia. Meanwhile, literature review identifies existing strategies to improve colorectal cancer screening. Additionally, the knowledge-to-action framework is integrated to ensure that the research findings lead to practical improvements to the colorectal cancer screening program. DISCUSSION: Through this complex mix of qualitative and quantitative methods, this study will explore the complex interplay of population- and systems-level factors that influence screening rates. It involves identifying barriers to effective colorectal cancer screening in Malaysia, comparing current strategies with international best practices, and providing evidence-based recommendations to improve the local screening program.

Early screening of colorectal cancer using feature engineering with artificial intelligence-enhanced analysis of nanoscale chromatin modifications.

Colonoscopy is accurate but inefficient for colorectal cancer (CRC) prevention due to the low (~ 7 to 8%) prevalence of target lesions, advanced adenomas. We leveraged rectal mucosa to identify patients who harbor CRC field carcinogenesis by evaluating chromatin 3D architecture. Supranucleosomal disordered chromatin chains (~ 5 to 20 nm, ~1 kbp) fold into chromatin packing domains (~ 100 to 200 nm, ~ 100 to 1000 kbp). In turn, the fractal-like conformation of DNA within chromatin domains and the folding of the genome into packing domains has been shown to influence multiple facets of gene transcription, including the transcriptional plasticity of cancer cells. We deployed an optical spectroscopic nanosensing technique, chromatin-sensitive partial wave spectroscopic microscopy (csPWS), to evaluate the packing density scaling D of the chromatin chain conformation within packing domains from rectal mucosa in 256 patients with varying degrees of progression to colorectal cancer. We found average packing scaling D of chromatin domains was elevated in tumor cells, histologically normal-appearing cells 4 cm proximal to the tumor, and histologically normal-appearing rectal mucosa compared to cells from control patients (p < 0.001). Nuclear D had a robust correlation with the model of 5-year risk of CRC with r2 = 0.94. Furthermore, rectal D was evaluated as a screening biomarker for patients with advanced adenomas presenting an AUC of 0.85 and 85% sensitivity and specificity. artificial intelligence-enhanced csPWS improved diagnostic performance with AUC = 0.90. Considering the low sensitivity of existing CRC tests, including liquid biopsies, to early-stage cancers our work highlights the potential of chromatin biomarkers of field carcinogenesis in detecting early, significant precancerous colon lesions.

Postcolonoscopy colorectal cancer: Prevalence, categorization and root-cause analysis based on the World Endoscopic Organization systemCáncer colorrectal poscolonoscopia / Prevalencia, categorización y análisis de las causas subyacentes basado en las recomendaciones de la Organización Mundial de Endoscopia

Aims: The World Endoscopy Organization (WEO) recommends that endoscopy units implement a process to identify postcolonoscopy colorectal cancer (PCCRC). The aims of this study were to assess the 3-year PCCRC rate and to perform root-cause analyses and categorization in accordance with the WEO recommendations.Patients and methods: Cases of colorectal cancers (CRCs) in a tertiary care center were retrospectively included from January 2018 to December 2019. The 3-year and 4-year PCCRC rates were calculated. A root-cause analysis and categorization of PCCRCs (interval and type A, B, C noninterval PCCRCs) were performed. The level of agreement between two expert endoscopists was assessed. Results: A total of 530 cases of CRC were included. A total of 33 were deemed PCCRCs (age 75.8±9.5 years; 51.5% women). The 3-year and 4-year PCCRC rates were 3.4% and 4.7%, respectively. The level of agreement between the two endoscopists was acceptable either for the root-cause analysis (k=0.958) or for the categorization (k=0.76). The most plausible explanations of the PCCRCs were 8 “likely new PCCRCs”, 1 (4%) “detected, not resected”, 3 (12%) “detected, incomplete resection”, 8 (32%) “missed lesion, inadequate examination”, and 13 (52%) “missed lesion, adequate examination”. Most PCCRCs were deemed noninterval Type C PCCRCs (N=17, 51.5%). Conclusion: WEO recommendations for root-cause analysis and categorization are useful to detect areas for improvement. Most PCCRCs were avoidable and were likely due to missed lesions during an otherwise adequate examination.(AU)

Objetivo: La Organización Mundial de Endoscopia recomienda que las unidades de endoscopia implementen procedimientos para identificar el cáncer colorrectal poscolonoscopia (CCRPC). Los objetivos de este estudio fueron evaluar la tasa de CCRPCP a los 3 y 4 años, realizar un análisis de causalidad potencial y categorización siguiendo las recomendaciones de la Organización Mundial de Endoscopia.Pacientes y métodos: Se incluyeron retrospectivamente los cánceres colorrectales diagnosticados de enero de 2018 a diciembre de 2019 en un hospital de tercer nivel. Se calculó la tasa de CCRPC a 3 años. Se realizó un análisis de causalidad potencial y categorización de los CCRPC (intervalo y CCRPC de no intervalo tipo A, B, C). Se evaluó la concordancia entre dos endoscopistas expertos. Resultados: Se incluyeron 530 cánceres colorrectales. Un total de 33 se consideraron CCRPC (edad 75,8±9,5 años; 51,5% mujeres). La tasa de CCRPC a 3 y 4 años fue del 3,4% y 4,7% respectivamente. La concordancia entre los dos endoscopistas fue aceptable para el análisis de causalidad (k=0,958) y para la categorización (k=0,76). La explicación probable de los CCRPC fue: 8 «probable CCRPC de novo», 1 (4%) «detectado, no resecado», 3 (12%) «detectado, resección incompleta», 8 (32%) «no detectado, examen inadecuado» y 13 (52%) «no detectado, examen adecuado». La mayoría de los CCRPC se consideraron de no intervalo tipo C (N=17, 51,5%). Conclusión: Las recomendaciones de la Organización Mundial de Endoscopia para el análisis de causalidad y la categorización son útiles para detectar áreas de mejora. La mayoría de los CCRPC eran evitables debido a lesiones no detectadas a pesar de realizar un examen adecuado.(AU)