Young Colorectal Cancer Patients Research Articles

Epigenetic Alteration in Colorectal Cancer: Potential Diagnostic and Prognostic Implications.

Colorectal cancer (CRC), a prevalent malignant tumor of the digestive system, ranks as the third and second in global incidence and mortality, respectively, in 2020, with 1.93 million new cases (≈10% of all cancers). There are 940,000 deaths (≈9.4% of all cancers), and the incidence of CRC in younger patients (under 50 years of age) has become a new trend. The pathogenesis of CRC is primarily attributed to a series of genetic and epigenetic abnormalities within normal colonic epithelial cells, coupled with the reshaping of the tumor microenvironment in the surrounding stroma. This process leads to the transformation of colorectal adenomas into invasive adenocarcinomas. Although genetic changes are known to be the primary driving force in the occurrence and progression of CRC, recent research indicates that epigenetic regulation serves as a crucial molecular marker in cancer, playing a significant role in the pathological and physiological control of interactions between genetics and the environment. This review discusses the current global epidemiology of CRC, its risk factors, and preventive treatment strategies. The current study explores the latest advancements in the epigenetic regulation of CRC, including DNA methylation, histone modifications, and non-coding RNAs (ncRNAs). These developments hold potential as screening tools, prognostic biomarkers, and therapeutic targets for CRC.

Health Literacy and Demand for Medical Cannabis use among Colorectal Cancer Patients in Northern Thailand: A Cross-Sectional Study.

This study aimed to explore health literacy and factors associated with demand for medical cannabis (MC) use among colorectal cancer (CRC) patients in Northern Thailand as a target group. This cross-sectional analytical study administered multistage random sampling to recruit 439 CRC patients in northern Thailand. Ethical approval and signed written informed consents were obtained from the patients, prior to the study. A standardized, self-administered structured questionnaire was used to obtain the sociodemographic characteristics, clinical characteristics, social support, attitudes toward MC, knowledge about MC, health literacy about MC, and questions on demand for MC use. The scores from all questionnaires were converted to percentages before analysis. A total of 146 (33.26%) of patients with CRC reported demand to use MC. The multivariable analysis revealed that factors associated with demand for MC among CRC patients included: had high levels of health literacy about MC (adj.OR = 7.71; 95% CI: 4.28 to 13.87), aged less than 45 years (adj.OR =5.09; 95% CI: 2.78 to 9.34), positive attitudes toward MC use (adj.OR = 4.66; 95% CI: 2.68 to 8.10), and higher levels of social support (adj.OR =4.14; 95% CI: 2.39 to 7.17) when controlling effect of other covariates. Health literacy is an important factor affecting the demand for MC use of CRC patients. Therefore, improving health literacy, social support, and attitudes about MC especially among younger CRC patients, could help increase demand for MC as a complementary and alternative medicine alongside cancer treatment.

Localized Rectal Cancer: Indian Consensus and Guidelines

AbstractThe rising incidence of colorectal cancer (CRC) in India, particularly the prevalence of rectal cancer over colon cancer (0.7:1), has been a growing concern in recent decades; especially notable is the trend of increasing cases among young CRC patients. Given the diverse treatment approaches for rectal cancer globally and the varying economic capacities of patients in low to middle-income countries (LMICs) like India, it is essential to establish consensus guidelines that are specifically tailored to meet the needs of these patients. To achieve this, a panel comprising 30 eminent rectal cancer experts convened to conduct a comprehensive and impartial evaluation of existing practices and recent advancements in the field. Through meticulous scrutiny of published literature and a consensus-building process that involved voting on pertinent questions, the panel formulated management strategies. These recommendations are the result of a rigorous, evidence-based process and encapsulate the collective wisdom and judgment of leading authorities in the field.

Clinicopathological features and prognoses in younger and older patients with mismatch repair defects colorectal cancer: a retrospective comparative cohort study.

Microsatellite instability-high (MSI-H) is an important biomarker for predicting the effects of immune checkpoint inhibitors (ICIs) in colorectal cancer (CRC) patients. However, due to the low mutation rate of MSI-H/deficient mismatch repair (dMMR) in the overall population, some doctors are of the view that testing this indicator increases the burden on patients, and consequently some patients fail to receive the most beneficial treatment methods. In order to provide testing criteria for younger patients with a higher proportion of MSI-H, we designed this retrospective controlled study. A retrospective analysis was conducted of 1,901 patients who were admitted to the Affiliated Cancer Hospital of Zhengzhou University from January 2017 to December 2019 and underwent CRC-related gene testing. For this analysis, 100 patients aged 40 or younger are defined as the young group, and 305 patients aged 71 and older but younger than 80 are defined as the elderly group. We included patients who met the following criteria: (I) underwent preoperative colonoscopy or gastroscopy and were diagnosed with CRC; (II) received perioperative adjuvant therapy; (III) underwent curative surgery for CRC. Each patient was followed up from the time of surgery until April 30, 2023, or death, with follow-up visits scheduled every 3 months for the first 2 years after surgery, and every 6 months thereafter. Clinical characteristics such as age, gender, body mass index (BMI), tumor depth (T), number of metastatic lymph nodes (N), distant metastasis (M), tumor, node, metastasis (TNM) stage, extent of surgical resection, tumor size, tumor location, differentiation grade, and carcinoembryonic antigen (CEA) levels were collected. The microsatellite instability (MSI) status was analyzed using fluorescence in situ hybridization (FISH). In young CRC patients, the proportion of MSI-H is higher than in elderly CRC patients (33% vs. 10.16%, P<0.001). The proportion of poorly differentiated tumors is also higher in young CRC patients compared to elderly CRC patients (53% vs. 31.15%, P<0.001). However, there were no significant differences in clinical characteristics between young and elderly CRC patients. In terms of prognosis, survival analysis of the young group showed that MSI status [hazard ratio (HR) =0.26, 95% confidence interval (CI): 0.08-0.88, P=0.03], TNM staging (HR =3.84, 95% CI: 1.38-10.71, P=0.010) were associated with the prognosis of CRC patients. The mutation rate of MSI-H is higher in young CRC patients compared to older. Our study further confirms that MSI-H can serve as a favorable prognostic marker for CRC patients. This finding may provide valuable guidance for clinicians in terms of prognosis assessment and treatment selection. If feasible, we hope that MSI testing can be performed for all CRC patients to enable targeted testing, with particular attention to monitoring the MSI status in young patients. This will aid clinicians in selecting appropriate treatment strategies for these patients.

Comparative genomic analysis to identify a signature of sporadic colorectal cancer development in young adults.

208 Background: Young-onset sporadic CRC is an important yet understudied heterogeneous group of aggressive cancers with distinct clinical and histopathological features. There is a steady increase in the incidence of cancer in this group of patients and currently, there are no screening guidelines to identify these patients due to a lack of understanding of the molecular mechanisms driving cancer in this patient group. Introduction: Despite screening guidelines and recent advances in cancer treatment, colorectal cancer (CRC) remains the second most diagnosed cancer and the second and third leading cause of cancer-related mortality in Canadian men and women, respectively [Canadian Cancer Statistics 2017.]. More striking is the rise in incidence of CRC in young adults in the United States [Siegel, R.L., et al, Bailey, C.E., et al., Dozois, E.J., et al., Deen, K.I., et al.], and the expectation that by the year 2030, the incidence rate will increase by 90% in this patient population. Data from the Surveillance and Cancer registry at Cancer Care Ontario shows a similar trend with increased rates in younger adults (ages 30 to 49) by 5.2 per cent per year between 2005 and 2012 [Ontario, C.C., Cancer Fact.]. Moreover, these younger patient groups are often diagnosed with aggressive forms and advanced stages of the disease [Ontario, C.C., Cancer Fact.]. Methods: In this study, using a total of 30 colorectal cancer patient samples from Windsor Regional Hospital Cancer Program, we performed comprehensive targeted gene sequencing to identify single nucleotide variants, small insertions/deletions, copy number variants in over 500 genes that are implicated in cancer. Mean age of the patients in this study was 44 years and only patients without any personal or family history of colon cancer /other malignancies or IBD were enrolled in the study. Results: While identifying previously known colorectal cancer associated genetic variants, our preliminary data shows distinct missense mutations in several genes potentially contributing to the development and progression of cancer in these patients. In addition to showing pathogenic mutations in colorectal cancers associated genes, such as PIK3CA (H1047R, E545K, E545G, R93W, V344A), KRAS (G12V, G12D, A146T) and APC, our study showed recurring missense mutations in several genes including AXIN2, ALK, CDKN1A, MAP3K1, ROS1, EPCAM, KDM5A and AURKA in over 50% of our samples. Conclusions: The genomic profiling performed using biopsies from young colorectal cancer patients through this study provides a unique ability to identify the potential “genomic triggers” for the development and progression of cancer in young sporadic colorectal cancer patients. This information can not only be used to develop targeted treatment options for these patients but also to design new screening protocols as well as optimal surveillance strategies.

Genetic insights: High germline variant rate in an indigenous African cohort with early-onset colorectal cancer

IntroductionThe increase in incidence of colorectal cancer in young patients of African ancestry coupled with increased aggressiveness has warranted investigation of the heritable nature of these cancers. Only a limited number of published reports of hereditary colorectal cancer in indigenous African populations have been reported and no systematic screening of these groups has been performed previously. We aimed to investigate causative germline variants and to establish the incidence of pathogenic/likely pathogenic germline variants in the known colorectal cancer genes in indigenous African colorectal cancer patients using a next-generation sequencing (NGS) multigene panel.Materials and methodsPatients were selected from two hospitals in Cape Town and Johannesburg, South Africa. Patients with unresolved molecular diagnosis with an age of onset below or at 60 years were selected. Germline DNA samples were analyzed using a 14-gene NGS panel on the Ion Torrent platform. Variant calling and annotation were performed, and variants were classified according to the American College of Medical Genetics and Genomics guidelines. Observed variants were verified by Sanger sequencing and/or long-range PCR.ResultsOut of 107 patients, 25 (23.4%) presented with a pathogenic/likely pathogenic germline variant (PGV). Fourteen PGVs in at least one mismatch repair (MMR) gene were identified and verified in 12 patients (11.2%). Of these MMR gene variants, five were novel. The remaining 10 PGVs were in the APC, BMPR1A, MUTYH, POLD1, and TP53 genes.ConclusionThe high incidence of PGVs associated with early-onset colorectal cancer in indigenous African patients has important implications for hereditary colorectal cancer risk management. These findings pave the way for personalized genetic screening programs and cascade testing in South Africa. The next step would involve further screening of the unresolved cases using tools to detect copy number variation, methylation, and whole exome sequencing.

Fertility preservation in reproductive-aged female patients with colorectal cancer: a scoping review.

Colorectal cancer (CRC) incidence in adults younger than 50 years is steadily increasing in the USA, and treatment for CRC can impact future fertility. However, fertility decision-making in female patients with CRC can be complex, with fertility preservation (FP) counseling occurring inconsistently. The goal of this scoping review was to assess the literature regarding the frequency and quality of fertility preservation (FP) discussions taking place among oncology clinicians and their reproductive-age female patients with colorectal cancer (CRC) in order to identify existing gaps in care and inform future research, interventions, or potential changes in practice. A comprehensive literature search was conducted using the Ovid Medline, PsycInfo, and Scopus databases in order to identify studies pertaining to FP counseling in reproductive-age female patients with CRC. We used Covidence to screen studies for relevance and to extract data. Findings of interest included rate of fertility and/or FP discussions, patient characteristics associated with fertility discussions, initiators of discussions, rate of referrals to fertility specialists, patient utilization of FP services, and unmet fertility needs. We performed both quantitative and qualitative data synthesis. We identified five studies that met our inclusion criteria, all published between 2007 and 2022. Frequency of fertility counseling discussions was low across studies, with a range of 15 to 52.5% of female patients with CRC receiving counseling. Patient characteristics which may be associated with likelihood of fertility discussion included age, parity, number of children, cancer location and stage, treatment type, and quality of life. The literature suggested that fertility discussions were initiated by clinicians about two-thirds of the time, and medical oncologists were the clinicians most likely to initiate. Studies did capture unmet fertility-related patient needs; participants who did not receive counseling often expressed desire for these discussions and regret that they did not occur. Despite increasing incidence of CRC in patients at younger ages, this scoping review found a dearth of research conducted on young female CRC patients' experiences with fertility counseling and referrals. Notably, the existing research reveals that relatively few of these patients are receiving appropriate counseling. Additional research is needed to clarify current FP counseling practices, patient and clinician perceptions about FP, and ways to improve the quantity and quality of FP counseling in this patient population.

Comparison of Selected Older and Younger Patients Regarding Optimal Surgical Treatment of Colorectal Cancer: A Prospective Cohort Study.

Current evidence regarding the optimal management of older colorectal cancer patients, is conflicting. Functional deficits impact long-term survival prognosis, while frailty often results to optimal treatment postponement. Thus, the characteristics of this subgroup combined with treatment deviations further perplex optimal oncological management. The study aim was to compare survival and optimal surgery rates between older and younger colorectal cancer patients. This study was designed as a prospective cohort. All adult (³18 years) colorectal cancer patients operated, during the 2016-2020 period, in the Department of Surgery, University Hospital of Larissa, were considered as eligible. The primary endpoint of the study was the difference in terms of the overall survival between older (>70 year) and younger (<70 years) colorectal cancer patients. Overall, 166 patients (60 younger and 106 older) were enrolled. Although the older subgroup displayed a higher rate (p=0.007) of ASA II and ASA III patients, mean CCI scores were comparable (p=0.384). The two subgroups were similar in terms of performed operations (p=0.140). No delay in surgery was noted. Most operations were performed using an open approach (open: 57.8% vs. laparoscopic: 42.2%), under an elective status (elective: 91% vs. emergency: 1.8%). There was no difference in terms of overall complications rate (p=0.859). Overall survival was similar (p=0.227) between the older and younger subgroups (25.68 vs. 28.48 months). Older operated patients did not differ from their younger counterparts with regard to their overall survival. Due to several study limitations, further trials are required to confirm these findings.

Readiness for return-to-work model-based analysis of return-to-work perception of young and middle-aged colorectal cancer patients with stoma in the early postoperative period: a descriptive qualitative study.

With an increase in the number of young and middle-aged colorectal cancer (CRC) patients with stoma, understanding their perception about return to work (RTW) in the early postoperative period can guide medical professionals to provide appropriate rehabilitation strategies, which can eventually improve patients' readiness for return to work (RRTW) and enable them to achieve final rehabilitation. The present study aimed to investigate the RTW-related perceptions and considerations of young and middle-aged CRC patients with stoma after surgery. From 2021 to 2022, we conducted a basic interpretive qualitative study involving semi-structured interviews with 17 CRC patients with stoma in two grade 3A hospitals in China. This study was based on the RRTW model. Data collection was continued until data saturation was reached, and all data were transcribed verbatim and analyzed by Colaizzi's phenomenological method. The following three key themes were identified: (1) self-efficacy; (2) decision balance; and (3) change process. Eight subthemes were formulated that were included within the respective main themes. In light of the current low self-efficacy and unsatisfactory willingness of patients with stoma about RTW, we suggest that medical staff should implement cognitive intervention and supportive interventions to improve self-efficacy, actively enhance the motivation of patients for RTW, and simultaneously resolve the pertinent difficulties; this could help patients to accept the positive change process and enable their successful transition from a change process to RTW.

Prediction models for overall and cancer-specific survival in patients with metastatic early-onset colorectal cancer: a population-based study

Metastatic early-onset colorectal cancer (EO-CRC) is on the rise, yet there is a dearth of predictive models for this disease. Therefore, it is crucial to develop a nomogram to aid in the early detection and management of metastatic colorectal cancer in young patients. We retrieved data from the SEER database on patients with metastatic colorectal cancer aged 50 or younger between 2010 and 2017. The data were randomly allocated in a 7:3 ratio to training and validation cohorts, and univariate and multivariate Cox regression analyses were used to identify independent prognostic factors for overall survival (OS) and cancer-specific survival (CSS) at 1, 3, and 5years. The nomograms were developed based on these factors, and their discriminatory and calibration capabilities were validated. Using the nomogram risk scores, patients were stratified into low-risk and high-risk groups. The study included 2470 patients with metastatic EO-CRC. Univariate and multivariate Cox regression analysis identified 12 independent risk factors that were included in the nomogram. The training cohort had a consistency index (C-index) of 0.71, while the validation cohort had a C-index of 0.70, demonstrating good predictive accuracy. Calibration plots showed a high level of consistency between the observed and predicted values, with overlapping plots along the diagonal. The decision curve analysis (DCA) revealed that the nomogram had a high clinical application value. The novel nomograms were created to predict the prognosis of patients with metastatic EO-CRC, which can aid clinicians in developing more effective treatment strategies and contribute to more accurate prognostic assessments.

Age-related differences in employment, insurance, and financial hardship among colorectal cancer patients: a report from the ColoCare Study.

Employment and financial hardships are common issues for working-age colorectal cancer patients. We surveyed colorectal cancer survivors to investigate employment, insurance, and financial outcomes by age at diagnosis. Cross-sectional survey of six ColoCare Study sites regarding employment, insurance, and financial hardship outcomes. Eligible participants were 1 to 5years from colorectal cancer diagnosis. Diagnosis age (18-49, 50-64, 65+ years) with outcomes of interest were compared using chi-square and t-tests. Multivariable logistic and Poisson regressions were fit to examine association of demographic factors with any material/psychological hardship (yes/no) and the count of hardships. N = 202 participants completed the survey (age: 18-49 (n = 42, 20.8%), 50-64 (n = 79, 39.1%), 65+ (n = 81, 40.1%)). Most diagnosed age < 65 worked at diagnosis (18-49: 83%; 50-64: 64%; 65+ : 14%, p < 0.001) and continued working after diagnosis (18-49: 76%; 50-64: 59%; 65+ : 13%; p < 0.001). Participants age 18-49 reported cancer-related difficulties with mental (81.3%) and physical (89%) tasks at work more than those working in the older age groups (45%-61%). In regression models, among those reporting any hardship, the rates of material and psychological hardships were higher among those age 18-64 (Incidence Rate Ratios (IRR) range 1.5-2.3 vs. age 65+) and for those with < college (IRR range 1.3-1.6 vs. college +). Younger colorectal cancer patients are more likely to work after a cancer diagnosis and during cancer treatment, but report higher levels of financial hardship than older patients. Younger colorectal cancer patients may encounter financial hardship, thus may feel a need to work during and after treatment.

Construction of Exosome SORL1 Detection Platform Based on 3D Porous Microfluidic Chip and its Application in Early Diagnosis of Colorectal Cancer.

Exosomes are promising new biomarkers for colorectal cancer (CRC) diagnosis, due to their rich biological fingerprints and high level of stability. However, the accurate detection of exosomes with specific surface receptors is limited to clinical application. Herein, an exosome enrichment platform on a 3D porous sponge microfluidic chip is constructed and the exosome capture efficiency of this chip is ≈90%. Also, deep mass spectrometry analysis followed by multi-level expression screenings revealed a CRC-specific exosome membrane protein (SORL1). A method of SORL1 detection by specific quantum dot labeling is further designed and the ensemble classification system is established by extracting features from 64-patched fluorescence images. Importantly, the area under the curve (AUC) using this system is 0.99, which is significantly higher (p< 0.001) than that using a conventional biomarker (carcinoembryonicantigen(CEA), AUC of 0.71). The above system showed similar diagnostic performance, dealing with early-stage CRC, young CRC, and CEA-negative CRC patients.

Colorectal cancer in young patients below screening age – Demographic and socioeconomic factors associated with incidence and survival

BackgroundWhile early onset colorectal cancer (EOCRC) has previously been defined as CRC in patients younger than age 50, recent screening guidelines have been lowered to 45. With more younger patients aged 45–50 are now being screened, incidence trend and outcomes of very early EOCRC (20–44) remains unclear. MethodSurveillance, Epidemiology, and End Results database was analyzed between 2006 and 2016 using Joinpoint tool to evaluate annual percentage change (APC) in incident rates, focusing on race/ethnicity and socioeconomic status (SES). Cancer specific survival (CSS) was assessed using univariate and multivariate analysis. Results41,815 EOCRC patients met inclusion criteria. Incidence has increased significantly in both age groups (APC in age group 20–44 = 1.21 and 45–49 = 1.06). Increase incidence of very early EOCRC was observed in White and Hispanic racial/ethnic groups (ACP 1.68 and 2.63), as well as population from counties with high poverty, unemployment, language barrier, foreign born resident, and high school dropout rates (ACP 2.07, 1.87, 1.21, 1.28 and 2.02 respectively). Further, the 5-year CSS was worse in Black patients, and patients from counties with high poverty, unemployment and high school dropouts rates (Age group 20–44, 63.11%, 66.39%, 67.48% and 66.95% respectively). On multivariate analysis, living in high poverty counties was an independent risk factor for poorer CSS for very early EOCRC (HR 1.20, 95% CI 1.07–1.34, p = 0.002). Multivariate analysis was adjusted by sex, pathology type, site of disease, disease extension and surgical treatment history. ConclusionVery early EOCRC incidence increases in White, Hispanic and poor patients, and outcomes are worse for minority and low-income patients. Further study on very early EOCRC is needed among those patients.

The role of biomarkers to increase the detection of early-onset colorectal cancer

Colorectal cancer is the third most diagnosed cancer worldwide with an estimated 1.93 million cases diagnosed in 2020. Over the past few decades there has been a dramatic rise in the incidence of early onset colorectal cancer, defined as colorectal cancer diagnosed in those aged under 50 years. The largest predictor of survival is early stage at diagnosis, therefore ways to improve prompt diagnosis of early onset colorectal cancer at an early stage is an effective way of managing the impact of this rising disease. Diagnosing colorectal cancer in younger patients has unique challenges with patients falling outside the age of most screening programs and early symptoms of colorectal cancer being common, non-specific and initially intermittent. While colonoscopy remains the gold standard investigation, it is a limited and expensive resource, and current patterns of practice result in large numbers of patients being scoped unnecessarily. The development and use of new and novel non-invasive biomarkers may help (either alone or in combination) identify either symptomatic patients in primary care, or aid with screening asymptomatic patients to focus resources where they are needed most. This review discusses challenges around diagnosing early onset colorectal cancer, with an overview of both current and future methods that might help overcome these challenges. These include increased assessment of familial risk, and the measurement of different biomarkers including faecal haemoglobin, markers of inflammation, gut microbiota, and selected metabolites.

Time to diagnosis and treatment in younger adults with colorectal cancer: A systematic review.

BackgroundThe incidence of colorectal cancer is rising in adults <50 years of age. As a primarily unscreened population, they may have clinically important delays to diagnosis and treatment. This study aimed to review the literature on delay intervals in patients <50 years with colorectal cancer (CRC), and explore associations between longer intervals and outcomes.MethodsMEDLINE, Embase, and LILACS were searched until December 2, 2021. We included studies published after 1990 reporting any delay interval in adults <50 with CRC. Interval measures and associations with stage at presentation or survival were synthesized and described in a narrative fashion. Risk of bias was assessed using the Newcastle-Ottawa Scale, Institute of Health Economics Case Series Quality Appraisal Checklist, and the Aarhus Checklist for cancer delay studies.Results55 studies representing 188,530 younger CRC patients were included. Most studies used primary data collection (64%), and 47% reported a single center. Sixteen unique intervals were measured. The most common interval was symptom onset to diagnosis (21 studies; N = 2,107). By sample size, diagnosis to treatment start was the most reported interval (12 studies; N = 170,463). Four studies examined symptoms onset to treatment start (total interval). The shortest was a mean of 99.5 days and the longest was a median of 217 days. There was substantial heterogeneity in the measurement of intervals, and quality of reporting. Higher-quality studies were more likely to use cancer registries, and be population-based. In four studies reporting the relationship between intervals and cancer stage or survival, there were no clear associations between longer intervals and adverse outcomes.DiscussionAdults <50 with CRC may have intervals between symptom onset to treatment start greater than 6 months. Studies reporting intervals among younger patients are limited by inconsistent results and heterogeneous reporting. There is insufficient evidence to determine if longer intervals are associated with advanced stage or worse survival.OtherThis study’s protocol was registered with the Prospective Register of Systematic Reviews (PROSPERO; registration number CRD42020179707).

Metagenomic analysis of the fecal microbiome in colorectal cancer patients compared to healthy controls as a function of age.

Colorectal cancer (CRC) incidence is increasing in young patients without a clear etiology. Emerging data have implicated the fecal microbiome in CRC carcinogenesis. However, its impact on young onset CRC is poorly defined. We performed a meta-analysis of fecal metagenomics sequencing data from n= 692 patients with CRC and n= 602 healthy controls from eleven studies to evaluate features of the fecal metagenome associated with CRC. We hypothesized that known carcinogenic virulence factors (colibactin, fadA) and species abundance may be differentially enriched in young CRC patients relative to older CRC patients and controls. Summary odds ratios (OR) for CRC were increased with the presence of colibactin (OR 1.92 95% CI 1.08-3.38), fadA (OR 4.57 95% CI 1.63-12.85), and F. nucleatum (OR 6.93 95% CI 3.01-15.96) in meta-analysis models adjusted for age, gender, and body mass index. The OR for CRC for the presence of E.coli was 2.02 (0.92-4.45). An increase in the prevalence of Fusobacterium nucleatum (OR=1.40 [1.18; 1.65]) and Escherichia coli (OR=1.14 [1.02; 1.28]) per 10-year increase in age was observed in models including samples from both CRC and healthy controls. Species relative abundance was differentially enriched in young CRC patients for five species-Intestinimonas butyriciproducens, Holdemania filiformis, Firimicutues bacterium CAG 83, Bilophilia wadsworthia, and Alistipes putredinis. In this study, we observed strong associations with CRC status for colibactin, fadA, and Fusobacterium nucleatum with CRC relative to controls. In addition, we identified several microbial species differentially enriched in young colorectal cancer patients. Studies targeting the young CRC patients are warranted to elucidate underlying preclinical mechanisms.

Ovarian metastases in young women with colorectal cancer: a retrospective multicenter cohort study.

Previous studies indicated that approximately 3.4% of female colorectal cancer (CRC) patients are at increased risk of developing ovarian metastases (OM). It has been suggested that young women more frequently develop this form of metastatic disease. This study evaluated, in 6 Dutch hospitals, the proportion of young women with CRC who developed OM. In a cohort of 200 young (age ≤ 55) women with CRC, the proportion of patients diagnosed with synchronous or metachronous OM was calculated. This study revealed that 5% (n = 10) of young female CRC patients developed ovarian metastases resulting in a 5-year overall survival rate of approximately 40%. Furthermore, six patients had concurrent peritoneal metastases, five patients had bilateral ovarian metastases, and five patients had synchronous metastases, while the median time of the occurrence of metachronous metastases (n = 5) was 19months. This retrospective multicenter cohort study indicates that 5% of young women with CRC either present with or develop OM. This result appears to be clinically relevant and demonstrates the need for improved surveillance for young women diagnosed with CRC.

Prediction of Postoperative Survival in Young Colorectal Cancer Patients: A Cohort Study Based on the SEER Database.

Objective Our aim is to make accurate and robust predictions of the risk of postoperative death in young colorectal cancer patients (18-44 years old) by combining tumor characteristics with medical and demographic information about the patient. Materials and Methods We used the SEER database to retrieve young patients diagnosed with colorectal cancer who had undergone surgery between 2010 and 2015 as the study cohort. After excluding cases with missing information, the study cohort was divided in a 7 : 3 ratio into a training dataset and a validation dataset. To assess the predictive ability of each predictor on the prognosis of colorectal cancer patients, we used two steps of Cox univariate analysis and Cox stepwise regression to screen variables, and the screened variables were included in a multifactorial Cox proportional risk regression model for modeling. The performance of the model was tested using calibration curves, decision curves, and area under the curve (AUC) for receiver operating characteristic (ROC). Results After excluding cases with missing information (n = 23,606), a total of 11,803 patients were included in the study with a median follow-up time of 45 months (1-119). In the training set, we determined that ethnicity, marital status, insurance status, median annual household income, degree of tumor differentiation, type of pathology, degree of infiltration, and tumor location had independent effects on prognosis. In the training dataset, taking 1 year, 3 years, and 5 years as the time nodes, the areas under the working characteristic curve of subjects are 0.825, 0.851, and 0.839, respectively, and in the validation dataset, they are 0.834, 0.837, and 0.829, respectively. Conclusion We trained and validated a model using a large multicenter cohort of young colorectal cancer patients with stable and excellent performance in both training and validation datasets.

Young-onset colorectal cancer: Insights from an English population-based study.

Young colorectal cancer (CRC) patients are reported to have more aggressive disease, an advanced stage at diagnosis and conflicting survival outcomes. The aim of this study was to analyse the demographics, clinicopathological features and prognosis of young CRC at a population-based level in England. This is a retrospective review of all CRC patients using data from Public Health England collated from regional cancer registries in England between 2010 and 2014. Those aged 40 years and below were classified as young and those over 40 were classified as older. Overall, 167,501 patients had CRC. Of these, 3757 patients (2.2%) were young. Right-sided cancers were more common in younger patients (48.2% vs. 32.9%, p< 0.001). Favourable histological grade (well or moderately differentiated) was present in 83.1% and 73.5% of young and older patients, respectively. The percentage of young and older patients being diagnosed at an early stage (Stages 1 and 2) was similar at 40.6% vs. 42.9%. The 5-year age- and gender-adjusted relative survival (cancer specific) was significantly better for young patients when compared with older patients diagnosed with CRC. Additionally, overall 5-year survival was better for younger patients (71.6% and 47.2%, p< 0.001 in young and older CRC patients respectively). The increased right-sided colon cancer in young CRC patients in England warrants attention. Contrary to previous reports, they do not present at later stage. Young CRC patients have better overall and relative survival than older patients with CRC.

Incorporation of functional status, frailty, comorbidities and comedication in prediction models for colorectal cancer survival.

Limitations in functional status, frailty, multiple comorbidities and comedications are common among older colorectal cancer (CRC) patients. We investigated whether adding these factors could improve the predictive value of a reference model containing age, sex, tumor stage and location for prediction of 5-year overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), recurrence-free survival (RFS) and nondisease-specific survival (nDSS) for all CRC patients as well as for younger (<65 years) and older patients (≥65 years). Overall, 3410 CRC patients from the DACHS study were analyzed and area under receiver operating characteristic curves (AUC) and net reclassification improvements (NRI) were assessed. In prediction of OS, the reference model plus functional status was identified as the best model among all CRC patients (AUC: 0.762) and younger CRC patients (AUC: 0.820). In older CRC patients, comorbidity should additionally be added (AUC: 0.747). For nDSS, the reference model plus comorbidity and frailty had the best predictive performance in all CRC patients (AUC: 0.776). For the outcomes DFS (AUC: 0.727), DSS (AUC: 0.838) and RFS (AUC: 0.784), the reference model was already the best model in all CRC patients because no significant NRIs were observed. The pattern "The less CRC-specific the survival outcome and the older the CRC patients, the more relevant the inclusion of functional status, comorbidity, and frailty in CRC prognostic scores is" was observed. Thus, different nomograms for younger and older CRC patients for 1-, 3- and 5-year OS prognosis estimation are being suggested.