Trends in colorectal cancer screening compliance and incidence among 60- to 74-year-olds in China.

BACKGROUND: Compliance with colonoscopy among elderly individuals participating in colorectal cancer (CRC) screening programs is unsatisfactory, despite a high detection rate of bowel-related diseases. In this study, our aim was to analyze the impact of risk factors on the trends of compliance and detection rates in colonoscopy among high-risk individuals aged 60-74. METHODS: A retrospective study was conducted on the high-risk individuals aged 60-74 participating in the 2021 CRC screening program in Tianjin, China. Logistic regression analyses, including both univariate and multivariate analyses, were performed to explore the impact of different risk factors on colonoscopy compliance among the high-risk individuals. Besides, the study investigated the influence of various risk factors on the detection rates of bowel-related diseases among the high-risk individuals who underwent colonoscopy. RESULTS: A total of 24,064 high-risk individuals were included, and 5478 individuals received a free colonoscopy, with an overall compliance of 22.76%. Among them, the adenoma detection rate was 55.46%. Males and individuals with a positive FIT had high compliance and detection rates for CRC, advanced adenomas (AA), advanced colorectal neoplasia (ACN), and colorectal neoplasm (CN). Individuals aged 70-74 were associated with low compliance but high CRC, ACN, and CN detection rates. Individuals who reported a history of chronic constipation, bloody mucous, and CRC in first-degree relative showed high compliance but no significantwere associated with the detection rates of CRC, AA, and CN. CONCLUSION: This study reported several risk factors associated with the screening behaviors for CRC. Patterns and trends in CRC, AA, ACN, and CN compliance and detection rates correlate with risk factors.

Prevalence and risk factors of colorectal neoplasia in individuals aged 40-49 years: Findings from screening program in China.

BACKGROUND AND AIM: The incidence of colorectal cancer (CRC) in individuals under 50 is increasing worldwide. We conducted an analysis of colonoscopy findings in high-risk individuals under 50 in the CRC screening program in Tianjin, China, to determine the detection rate and risk factors of advanced adenomas (AA), advanced colorectal neoplasia (ACN), colorectal neoplasia (CN). METHODS: Our study investigated individuals aged 40-49 who underwent CRC screening and completed colonoscopy, 2012-2020, while the 50-54 age group served as a control. We compared the detection rates of AA, ACN, and CN among three age groups using univariate and multivariable logistic regression analyses, and investigated the risk factors associated with AA, ACN, and CN among individuals aged 40-49. RESULTS: We found a gradual increase in the detection rate of AA, ACN, and CN among individuals aged 40-54. The detection rates for AA (OR 0.58; 95% CI 0.41-0.81), ACN (OR 0.58; 95% CI 0.43-0.77), and CN (OR 0.64; 95% CI 0.56-0.74) were lower in individuals aged 40-44 compared to 45-49. The detection rates of AA (OR 1.08; 95% CI 0.87-1.34) and ACN (OR 1.12; 95% CI 0.93-1.35) in individuals aged 45-49 were comparable with 50-54. Besides, lifestyle factors, BMI, and FIT are not associated with the detection rates of AA, ACN, and CN among individuals aged 40-49. CONCLUSIONS: Our study reveals screening data in individuals under 50, indicating comparable detection rates of AA and ACN in individuals aged 45-49 and 50-54. These findings provide valuable data support for optimizing the optimal age to initiate screening.

Prognostic impact of colorectal cancer patients with bone metastases: a single-center experience.

The incidence of bone metastasis (BM) in colorectal cancer (CRC) patients is low and the prognosis is poor. There is no clear conclusion on the risk factors affecting the survival of CRC patients with BM. The aim of this study was to investigate the factors that may affect the prognosis of CRC patients with BM. The clinical and pathological data of CRC patients with BM were retrospectively analyzed. The overall survival after BM diagnosis was estimated using the Kaplan-Meier method and Log-rank test, and a multivariable cox regression model was used to identify the prognostic factors of overall survival. This study included 178 CRC patients with BM, of whom 151 had left-sided CRC and 27 had right-sided colon cancer. 1124 CRC patients with BM from the SEER database were included to perform a sensitivity analysis of the primary outcome. Multivariate analysis showed that the N staging, site of BM, and primary tumor sidedness (PTS) were independent prognostic factors for CRC with BM. Among them, right-sided colon cancer patients with BM had a poorer prognosis. Sensitivity analyses showed that PTS was an independent prognostic factor in CRC patients with BM. Primary tumor sidedness and N stage may be potential prognostic markers for BM of CRC. The prognosis of N0 stage CRC with BM is better, while the prognosis of right-sided colon cancer is poor.

Proteomic Profiling and Tumor Microenvironment Characterization Reveal Molecular and Immunological Hallmarks of Left-Sided and Right-Sided Colon Cancer Tumorigenesis.

Left-sided and right-sided colon cancer (LSCC and RSCC) display different biological and clinical characteristics. However, the differences in their tumorigenesis and tumor microenvironment remain unclear. In this study, we profiled the proteomic landscapes of LSCC and RSCC with data-independent acquisition mass spectrometry (DIA-MS) using fresh tumor and adjacent normal tissues from 24 patients. A total of 7403 proteingroups were primarily identified with DIA-MS. After quality control, 7212 proteingroups were used for further analysis. Through comparing the difference in proteomic profiles between LSCC and RSCC samples, 2556 commonly and 1982 region-type-specific regulated proteingroups were characterized. During the development of LSCC and RSCC, metabolic, growth, cell division, cell adhesion, and migration pathways were found to be significantly dysregulated (P < 0.05), which was further confirmed by transcriptome data from TCGA. Compared to RSCC, most parts of the immune-related signatures, immune cell infiltration scores, and overall immune scores of LSCC were higher. The systematic elucidation of proteomic and transcriptomic profiles in this work improves our understanding of tumorigenesis and immune microenvironment characteristics of LSCC and RSCC.

Postponing colonoscopy for 6 months in high-risk population increases colorectal cancer detection in China.

BACKGROUND AND AIMS: Colonoscopy is an important colorectal cancer (CRC) screening modality; however, not all high-risk groups identified by fecal immunochemical test (FIT) and/or high-risk factor questionnaire (HRFQ) undergo colonoscopy in time. The impact of delays in colonoscopy on CRC detection among high-risk populations remains poorly understood, warranting further clarification. METHODS: A retrospective study was conducted among CRC high-risk population identified by Tianjin CRC screening program. According to the colonoscopy results after HRFQ and FIT, patients were classified into CRC, advanced adenoma, non-advanced adenoma, and normal groups. The time interval between CRC screening and colonoscopy was investigated and its relationship with colonoscopy results. Logistic regression was performed to explore the risk factors of CRC detection. RESULTS: Among the high-risk population without a history of CRC or polyps, 49,810 underwent HRFQ, FIT, and colonoscopy, and a time interval of fewer than 6 months was found for 79.56% of patients (n = 39,630). People with positive FIT were more likely to undergo colonoscopy within 6 months, and detection rates of CRC and/or advanced adenoma were positively related to time intervals. Similar results were found in people with a negative FIT but positive HRFQ. A time interval longer than 6 months was a significant predictor of CRC detection in high-risk populations. CONCLUSION: For high-risk people identified by CRC screening, especially those with a positive FIT, a time interval of 6 months was associated with an increased probability of CRC detection. Our findings emphasize that populations at high risk should undergo colonoscopy at least within 6 months.

Predictive models based on machine learning for bone metastasis in patients with diagnosed colorectal cancer.

Background: This study aimed to develop an artificial intelligence predictive model for predicting the probability of developing BM in CRC patients. Methods: From SEER database, 50,566 CRC patients were identified between January 2015 and December 2019 without missing data. SVM and LR models were trained and tested on the dataset. Accuracy, area under the curve (AUC), and IDI were used to evaluate and compare the models. Results: For bone metastases in the entire cohort, SVM model with poly as kernel function presents the best performance, whose accuracy is 0.908, recall is 0.838, and AUC is 0.926, outperforming LR model. The top three most important factors affecting the model's prediction of BM include extraosseous metastases (EM), CEA, and size. Conclusion: Our study developed an SVM model with poly as kernel function for predicting BM in CRC patients. SVM model could improve personalized clinical decision-making, help rationalize the bone metastasis screening process, and reduce the burden on healthcare systems and patients.

Prognosis of Patients Over 60 Years Old With Early Rectal Cancer Undergoing Transanal Endoscopic Microsurgery - A Single-Center Experience.

Aim: Transanal endoscopic microsurgery (TEM) is widely performed in early rectal cancer. This technique offers greater organ preservation and decreases the risk of subsequent surgery. However, postoperative local recurrence and distant metastasis remain challenges for patients with high-risk pathological factors. This single-center study reports the prognosis of early rectal cancer patients over 60 years old after TEM. Methods: The data of the patients over 60 years old who underwent local anal resection were collected retrospectively. Moreover, the 5-year follow-up data were analyzed to determine the 5-year DFS and OS. Results: 47 early rectal cancer patients over 60 years old underwent TEM. There were 27 patients with high-risk factors and 20 patients without high-risk factors. Two patients underwent radical surgery after TEM and ten patients received adjuvant treatment. Local recurrence occurred in 7 patients, of which 4 underwent salvage surgery. The 5-year progression-free survival rate was 75.6%, which was lower in the high-risk patients group (69.6%) than in the non-high-risk patients group (83.3%) (P>0.05). The 5-year OS was 90.2%, but there was no statistically significant difference between the two groups (high-risk patients 87.0%, non-high-risk patients 94.4%). Furthermore, there was no significant difference in DFS and OS between people over and under 70 years old. Conclusion: Some high-risk factor patients over 60 years old do not have inferior 5-year DFS and OS to the non-high-risk patients. TEM is an option for old patients with high surgical risks. Even if postoperative pathology revealed high-risk factors, timely surgical treatment after local recurrence would be beneficial to improve the 5-year DFS and OS.

Colorectal Cancer Screening With High Risk-Factor Questionnaire and Fecal Immunochemical Tests Among 5, 947, 986 Asymptomatic Population: A Population-Based Study.

Background: The recent uptrend in colorectal cancer (CRC) incidence in China is causing an increasingly overwhelming social burden. And its occurrence can be effectively reduced by sensitizing CRC screening for early diagnosis and treatment. However, a large number of people in China do not undergo screening due to multiple factors. To address this issue, since 2012, a CRC screening program has been initiated in Tianjin. Methods: Residents aged 40-74 years were eligible for CRC screening. The first was to complete the high-risk factor questionnaire (HRFQ) and undergo fecal immunochemical test (FIT). Then those with a positive result in any of the two screening methods were recommended for a free colonoscopy. Results: The detection rate of intestinal diseases increased with age, had a male predominance, and was higher in residents from central urban areas and those with primary school above education level. The sensitivity of predicting CRC after colonoscopy in the high-risk group was 76.02%; the specificity was 25.33%.A significant decrease in the detection rate of intestinal disease, CRC and advanced adenoma was observed from positive FIT, the high-risk group and positive HRFQ, 47.13%, 44.79%, 42.30%; 3.15%, 2.44%, 1.76%; 7.72%, 6.42%, 5.08%, in that order, while no inter-group difference was found for the detection of polyps. In addition, the different combinations of HRFQ and FIT can enroll more high-risk population than FIT or (and) HRFQ only, and thus detect more intestinal diseases (include CRC/AA/Polyp). Conclusion: The superimposition of different screening method for HRFQ and FIT is an effective strategy for the detection of CRC, AA, and Polyp, compared to HRFQ or FIT alone. However, further improvements in screening and interventions are needed to promote colonoscopy compliance.

Self-targeting of zwitterion-based platforms for nano-antimicrobials and nanocarriers.

Self-targeting antimicrobial platforms have yielded new possibilities for the treatment of infectious biofilms. Self-targeting involves stealth transport through the blood circulation towards an infectious biofilm, where the antimicrobial platform penetrates and accumulates in a biofilm in response to a change in environmental conditions, such as local pH. In a final step, nano-antimicrobials need to be activated or the antimicrobial cargo of nanocarriers released. Zwitterions possess both cationic and anionic groups, allowing full reversal in zeta potential from below to above zero in response to a change in environmental conditions. Electrolyte-based platforms generally do not have the ability to change their zeta potentials from below to above zero. Zwitterions for use in self-targeting platforms are usually hydrophilic and have a negative charge under physiological conditions (pH 7.4) providing low adsorption of proteins and assisting blood circulation. However, near or in the acidic environment of a biofilm, they become positively-charged yielding targeting, penetration and accumulation in the biofilm through electrostatic double-layer attraction to negatively-charged bacteria. Response-times to pH changes vary, depending on the way the zwitterion or electrolyte is built in a platform. Self-targeting zwitterion-based platforms with a short response-time in vitro yield different accumulation kinetics in abdominal biofilms in living mice than platforms with a longer response-time. In vivo experiments in mice also proved that self-targeting, pH-responsive zwitterion-based platforms provide a feasible approach for clinical control of bacterial infections. Clinically however, also other conditions than infection may yield an acidic environment. Therefore, it remains to be seen whether pH is a sufficiently unique recognition sign to direct self-targeting platforms to an infectious biofilm or whether (additional) external targeting through e.g. near-infrared irradiation or magnetic field application is needed.

Ring finger protein 2 promotes colorectal cancer progression by suppressing early growth response 1.

Ring finger protein 2 (RNF2) is an important component of polycomb repressive complex 1. RNF2 is upregulated in many kinds of tumors, and elevated RNF2 expression is associated with a poor prognosis in certain cancers. To assess the function of RNF2 in colorectal cancer, we examined RNF2 protein levels in 313 paired colorectal cancer tissues and adjacent normal tissues. We then analyzed the association of RNF2 expression with the patients' clinicopathologic features and prognoses. RNF2 expression was upregulated in colorectal cancer tissues and was associated with the tumor differentiation status, tumor stage and prognosis. In colorectal cancer cell lines, downregulation of RNF2 inhibited cell proliferation and induced apoptosis. Gene microarray analysis revealed that early growth response 1 (EGR1) was upregulated in RNF2-knockdown cells. Knocking down EGR1 partially reversed the inhibition of cell proliferation and the induction of apoptosis in RNF2-knockdown cells. RNF2 was enriched at the EGR1 promoter, where it mono-ubiquitinated histone H2A, thereby inhibiting EGR1 expression. These results indicate that RNF2 is oncogenic in colorectal cancer and may promote disease progression by inhibiting EGR1 expression. RNF2 is thus a potential prognostic marker and therapeutic target in colorectal cancer.