BACKGROUND:Uterine fibroids (UFs), the most common tumors in women worldwide, may reduce quality of life and daily activities and even lead to adverse fertility and general health events in patients, causing significant societal health and financial burdens. The objective of this study was to evaluate the global burden through epidemiological trends and examine the potential risk factors for UFs at the national level. METHODS:Data on the incidence, prevalence, disability-adjusted life years (DALYs), age-standardized incidence rates (ASIRs), age-standardized prevalence rates (ASPRs), and age-standardized DALY rates for UFs were collected, and the associations with the Human Development Index (HDI) and fertility were evaluated. The age trends in the average annual percent change (AAPC) of the incidence and prevalence rates of UFs were evaluated by joinpoint regression analysis. The associations between lifestyle, metabolic, and socioeconomic factors and the ASIRs of UFs were examined using multivariable linear regression analysis. RESULTS:The worldwide incidence and prevalence of UFs have been increasing in the past decade, with AAPCs of 0.27% in the incidence rate and 0.078% in the prevalence rate. During 2010-2019, significant increasing trends in UF ASIR were observed in 52 of 88 countries. The age-specific incidence and prevalence of UFs in most age groups showed increasing trends except for 45-54-year-old women which showed no significant trend. Ecological analysis demonstrated no relationship between the incidence of UFs and the HDI but an inverse association with fertility. The incidence of UFs was positively correlated with alcohol intake, hypertension, overweight, and obesity and negatively correlated with smoking. CONCLUSION:With the increasing incidence and prevalence worldwide, effective targeted prevention and control of relevant risk factors at the national level should be encouraged to reduce the disease burden of UFs.

BACKGROUND & AIMS: The screening yield and related cost of a risk-adapted screening approach compared with established screening strategies in population-based colorectal cancer (CRC) screening are not clear.METHODS: We randomly allocated 19,373 participants into 1 of the 3 screening arms in a 1:2:2 ratio: (1) one-time colonoscopy (n = 3883); (2) annual fecal immunochemical test (FIT) (n = 7793); (3) annual risk-adapted screening (n = 7697), in which, based on the risk-stratification score, high -risk participants were referred for colonoscopy and low-risk ones were referred for FIT. Three consecutive screening rounds were conducted for both the FIT and the risk-adapted screening arms. Follow-up to trace the health outcome for all the participants was conducted over the 3 -year study period. The detection rate of advanced colorectal neoplasia (CRC and advanced precancerous lesions) was the main outcome. The trial was registered in the Chinese Clinical Trial Registry (number: ChiCTR1800015506).RESULTS: In the colonoscopy, FIT, and risk-adapted screening arms over 3 screening rounds, the partici-pation rates were 42.4%, 99.3%, and 89.2%, respectively; the detection rates for advanced neoplasm (intention-to-treat analysis) were 2.76%, 2.17%, and 2.35%, respectively, with an odds ratio (OR)colonoscopy vs FIT of 1.27 (95% confidence interval [CI]: 0.99-1.63; P = .056), an ORcolonoscopy vs risk-adapted screening of 1.17 (95% CI, 0.91-1.49; P = .218), and an ORrisk-adapted screening vs FIT of 1.09 (95% CI, 0.88-1.35; P = .438); the numbers of colonoscopies needed to detect 1 advanced neoplasm were 15.4, 7.8, and 10.2, respectively; the costs for detecting 1 advanced neoplasm from a government perspective using package payment format were 6928 Chinese Yuan (CNY) ($1004), 5821 CNY ($844), and 6694 CNY ($970), respectively. CONCLUSIONS: The risk-adapted approach is a feasible and cost-favorable strategy for population-based CRC screening and therefore could complement the well-established one-time colonoscopy and annual repeated FIT screening strategies. (Chinese Clinical Trial Registry; ChiCTR1800015506).

Objective To evaluate the feasibility and effectiveness of colonoscopy, fecal immunochemical test(FIT) and risk-adapted screening strategies in population-based colorectal cancer screening. Methods Based on the randomized controlled trial of colorectal cancer screening(TARGET-C) which was carried out in 6 centers of 5 provinces in China from May 2018 to May 2021, the participants who met the inclusion criteria of the study were randomly assigned to one of the following screening intervention groups in a ratio of 1∶2∶2, which were colonoscopy group, FIT group and risk-adapted screening group(participants evaluated to be at high risk were recommended to undertake colonoscopy, those at low risk were recommended to undertake FIT and FIT positive people received colonoscopy). The 3 groups received different schemes of colorectal cancer screening, in which the colonoscopy group only received baseline screening, whereas the FIT group and the risk-adapted screening group received annual follow-up screening on the basis of baseline screening. The main outcome was the detection rate for advanced colorectal neoplasm(including colorectal cancer and advanced adenoma). The participation rate, detection rate for any neoplasm and resource load of colonoscopy among different screening groups were further analyzed. Results A total of 19 373 participants meeting the inclusion and exclusion criteria were enrolled, including 8082 males(41.7%) and 11 291 females(58.3%), with an average age of (60.5±6.5) years. Among them, 3883 were in the colonoscopy group, 7793 in the FIT group, and 7697 in the risk-adapted screening group. After 1 or 3 rounds of screening(2 rounds of follow-up screening completed in FIT group and risk-adapted screening group), the overall participation was the highest for the FIT group(99.3%), followed by the risk-adapted screening group(89.2%) and the coloscopy group(42.3%). According to the intention-to-treat analysis, the detection rates of advanced neoplasm in the colonoscopy group was higher than that in the FIT group(2.76% vs. 2.17%, ORcolonoscopy vs FIT=1.30, 95% CI: 1.01-1.65, P=0.037); there were no statistically significant differences regarding the detection rates of advanced neoplasm between the colonoscopy group and the risk-adapted screening group(2.76% vs. 2.35%, ORcolonoscopy vs risk-adapted screening=1.19, 95% CI: 0.93-1.51, P=0.156), and between the risk-adapted screening group and the FIT group(2.35% vs. 2.17%, ORrisk-adapted screening vs FIT=1.09, 95% CI: 0.88-1.34, P=0.440). The number of colonoscopies needed to be performed to detect one advanced neoplasm was used as an indicator to evaluate the resource load of colonoscopy. The number was the highest for the coloscopy group(15.4), followed by the risk-adapted screening group(10.2) and the FIT group(7.8). Conclusions The risk-adapted screening strategy is feasible and effective in population-based colorectal cancer screening, and could serve as an effective supplement to the traditional colonoscopy and FIT-based colorectal cancer screening strategies.

Background Evidence of temporal changes in the gut microbiome and circulating metabolome alterations in colorectal precancerous lesions before and after treatment is sparse. We, therefore, aimed to investigate the fecal microbial and plasma metabolomic signatures associated with colorectal adenomas and their temporal changes in advanced colorectal adenomas (AA) before and after polypectomy. Methods We included 386 AAs, 324 patients with non-advanced adenoma (NAA), and 329 healthy controls (HC) in a population-based colorectal cancer screening trial. A sub-cohort of 84 AAs who underwent polypectomy at baseline had repeated colonoscopies after two years. All fecal and plasma samples were collected before diagnosis. Omics markers were identified using metagenomics and metabolomics data with validations in the open-source dataset. Temporal changes in AA-related omics signatures were compared in 84 AAs between baseline and two-year after polypectomy (IDDF2023-ABS-0104 Figure 1 (A) Diagram of the study design and data collection (B) Workflow of data analyses). Results We identified elevated abundances of Bacteroides xylanisolvens, Parabacteroides merdae, Parabacteroides distasonis, Flavonifractor plautii, Clostridium symbiosum, and Bacteroides intestinalis in AAs (IDDF2023-ABS-0104 Figure 2. Characteristic of fecal microbiome in AAs, NAAs and HCs (species level). (A) Alpha diversity indices; (B) Gut microbiome similarities; (C-D) Comparisons of gut microbial species between AAs and HCs/NAAs; (E) Log10-transformed relative abundances of the nine differential species), which remained at the same level two-year after polypectomy (p>0.05), as well as nearly half of the AA-related plasma metabolites. We further constructed gut microbial species- and plasma metabolite-based prediction models for AA. However, risks predicted by AA-related gut microbial and plasma metabolic signatures were stable in AAs before and two-year after polypectomy (IDDF2023-ABS-0104 Figure 3. Risks of AA predicted by AA-related gut microbial species and plasma metabolites in AA patients who had no findings of adenoma in repeated colonoscopies (A), or who were diagnosed with NAA in repeated colonoscopies (B), or who were diagnosed with AA in repeated colonoscopies (C)). Conclusions Gut microbial signatures associated with AA remained stable for two years after polypectomy, indicating the significance of gut microbiota reconstruction in CRC prevention.

BACKGROUND:Female breast cancer (FBC) has become the most prevalent malignancy worldwide. We aimed to evaluate the global and regional burden in epidemiological trends and factors associated with the incidence and mortality of FBC.METHODS:FBC incidence and mortality in 60 selected countries by cancer registry data integrity in 2020 were estimated from the GLOBOCAN database, and their association with the human development index (HDI) was further evaluated. Trends of age-standardized rates of incidence and mortality in 60 countries from 2000 through 2019 were evaluated by joinpoint regression analysis using data of Global Burden of Disease 2019. The association between potential behavioral, metabolic, and socioeconomic risk factor exposure at the nation level retrieved from the World Bank and Global Health Observatory and the incidence and mortality of FBC were evaluated by multivariate linear regression.RESULTS:FBC incidence and mortality varied greatly in the 60 included countries. Higher incidence and mortality rates were typically observed in countries with higher HDIs and vice versa. During 2000 to 2019, significantly increasing trends in incidence and mortality were observed in 26 (average annual percent changes [AAPCs], 0.35-2.96) and nine countries (AAPC, 0.30-1.65), respectively, while significantly decreasing trends in both incidence and mortality were observed in 22 countries, most of which were high-HDI countries. Among the population aged ≥40 years, there were 26 and 11 countries showing significantly increased trends in incidence and mortality, respectively. Ecological analysis showed that countries with higher prevalence rates of high cholesterol and higher health expenditures were more likely to have higher FBC incidence, and countries with higher rates of obesity and poorer universal health coverage were more likely to have higher FBC mortality.CONCLUSIONS:Despite decreased or stabilized FBC incidence and mortality rates were observed in some countries with high HDI over the past decades, disease burden became even severer in developing countries, especially for the population aged ≥40 years. Effective targeted preventive programs are strongly encouraged to reduce the FBC disease burden worldwide.

The influence of long-term diet on gut microbiota is an active area of investigation. The present work aimed to explore the associations between habitual diet patterns and gut microbiota in a large sample of asymptomatic Chinese adults. The gut microbiome was profiled through the sequencing of the 16S rRNA gene in stool samples from 702 Chinese adults aged 50–75 years who underwent colonoscopies and were diagnosed to be free of colorectal neoplasm. Long-term dietary consumption was assessed through a food-frequency questionnaire. The microbial associations with specific food groups and the posteriori dietary pattern were tested using the Kruskal–Wallis H test, permutational ANOVAs, and multivariate analyses with linear models. The Shannon indexes generally shared similar levels across different food intake frequency groups. Whole grain and vegetable intakes totally explained 1.46% of the microbiota compositional variance. Using the data-driven posteriori approach, a general dietary pattern characterized by lower intakes of refined grains was highlighted to be associated with higher abundances of the genus Anaerostipes and a species of it. We also observed 17 associations between various food group intakes and specific genera and species. For instance, the relative abundances of the genus Weissella and an uncultured species of it were negatively associated with red meat intake. The results of this study support the idea that the usual dietary consumption measured by certain food items or summary indexes is associated with gut microbial features. These results deepen the understanding of complex relationships of diet and gut microbiota, as well as their implications for gut microbiome studies of human chronic diseases.

IntroductionA microsimulation model provides important references for decision-making regarding colorectal cancer (CRC) prevention strategies, yet such a well-validated model is scarce in China. MethodsWe comprehensively introduce the development of MIcrosimulation Model for the prevention and Intervention of Colorectal Cancer in China (MIMIC-CRC). The MIMIC-CRC was first constructed to simulate the natural history of CRC based on the adenoma-carcinoma pathway. The parameters were calibrated and validated using data from population-based cancer registry data and CRC screening programs. Furthermore, to assess the model's external validity, we compared the model-derived results to outcome patterns of a sigmoidoscopy screening trial in the UK [UK Flexible Sigmoidoscopy Screening (UKFSS) trial]. Finally, we evaluated the application potential of the MIMIC-CRC model in CRC screening by comparing the 8 different strategies. ResultsWe found that most of the model-predicted colorectal lesion prevalence was within the 95% CIs of observed prevalence in a large population-based CRC screening program in China. In addition, model-predicted sex- and age-specific CRC incidence and mortality were equivalent to the registry-based data. The hazard ratios of model-estimated CRC-related incidence and mortality for sigmoidoscopy screening compared to no screening were 0.60 and 0.51, respectively, which were comparable to the reported results of the UKFSS trial. Moreover, we found that all 8 strategies could reduce CRC incidence and mortality compared to no screening. ConclusionsThe well-calibrated and validated MIMIC-CRC model may represent a valid tool to assess the comparative effectiveness of CRC screening strategies and will be useful for further decision-making to CRC prevention.

The risk‐adapted screening strategy showed satisfying colorectal cancer (CRC) screening yield and efficiency. We therefore further explored the diagnostic performance variation of this strategy using different risk prediction models.

Background: An emerging increasing trend of pancreatic cancer (PC) incidence in young adults is reported in some countries. This study aims to describe the global trend of PC among young adults and to explore the related factors. Methods: Global and national data on PC incidence, disability-adjusted life-years, and attributive mortality were retrieved from the Global Burden of Disease 2019. The average annual percent change (AAPC) in incidence and mortality were estimated. Generalized additive models were applied to explore the non-linear associations between level, and change, of Human Development Index (HDI) and AAPC. Findings: Global PC incidence showed an increase during different periods from 1990 to 2019, especially in adults younger than 45 years old from 2010 to 2019, with an average increase rate of 0.69% per year (95% CI: 0.35 to 1.03). The AAPC of early-onset PC incidence during 2010–2019 was negatively correlated with HDI levels both in 2010 and 2019, while being positively correlated with HDI acceleration during that period. Significant increasing trends of early-onset PC incidence were observed over this period in 32 of 88 countries, mainly in South America, North America, Oceania, and Africa. Early-onset PC mortality attributed to high body mass index (BMI) and fasting plasma glucose (FPG) were increasing, while that attributed to tobacco use was declining. Interpretation: An emerging increasing trend has appeared in the global incidence and burden of early-onset PC over the last decades, which could be partly explained by the global epidemic of high BMI and FPG. Funding: CAMS Innovation Fund for Medical Sciences (CIFMS) 2021-I2M-1-002. Declaration of Interest: We declare no competing interests.

Breast cancer (BC) is the most prevalent malignancy worldwide, and a continued upward trend has been predicted in the coming decades. Screening in selected targeted populations, which is effective in reducing cancer-related mortality, has been widely implemented in many countries. This review summarizes the advances in BC screening techniques, organized or opportunistic BC screening programs across different countries, and screening modalities recommended by different academic authorities. Mammography is the most widely used and effective technique for BC screening. Other complementary techniques include ultrasound, clinical breast examination, and magnetic resonance imaging. Novel screening tests, including digital breast tomosynthesis and liquid biopsies, are still under development. Globally, the implementation status of BC screening programs is uneven, which is reflected by differences in screening modes, techniques, and population coverage. The recommended optimal screening strategies varied according to the authoritative guidelines. The effectiveness of current screening programs is influenced by several factors, including low detection rate, high false-positive rate, and unsatisfactory coverage and uptake rates. Exploration of accurate BC risk prediction models and the development of risk-stratified screening strategies are highly warranted in future research.

Hyperglycemia has been reported to increase the risk of pancreatic cancer (PC), while the association between glycemic change and PC risk has rarely been explored. Using data from a prospective cohort study conducted in China since 2006, 138,870 males with available fasting blood glucose (FBG) levels, including 106,632 males with at least two FBG measurements, were analyzed. The associations between FBG (level, change, and stability) and PC incidence were evaluated using Cox proportional hazard regression and restricted cubic splines. Baseline (p = 0.109) and recent (p = 0.070) FBG levels and incident PC were not significantly associated. U-shaped associations were observed between the annual FBG change and PC risk. Compared with stable FBG, participants with annual FBG change rates <−0.05 mmol/L or >0.15 mmol/L had about four-fold (HR, 4.010; 95% CI: 1.920−8.375) and six-fold (HR, 5.897; 95% CI: 2.935−11.848) higher PC risks, respectively. The PC risk increased by 2.5% (HRlinear = 1.025, 95% CI:1.009−1.042) for every 1% increase in the coefficient of variation for FBG. A subgroup analysis of males without diabetes at baseline showed stronger associations. Temporal FBG changes may be an important factor for identifying populations with high PC risks.

BACKGROUND:Globally, colorectal cancer (CRC) imposes a substantial burden on healthcare systems and confers considerable medical expenditures. We aimed to evaluate the global and regional burden in epidemiological trends and factors associated with the incidence and mortality of CRC.METHODS:We used data from the GLOBOCAN database to estimate CRC incidence and mortality worldwide in 2020 and their association with the human development index (HDI). Trends of age-standardized rates of incidence and mortality in 60 countries (2000-2019) were evaluated by Joinpoint regression analysis using data of Global Burden of Disease 2019. The association between exposure to country-level lifestyle, metabolic and socioeconomic factors obtained from the World Health Organization Global Health Observatory and World Bank DataBank data and CRC incidence and mortality was determined by multivariable linear regression.RESULTS:CRC incidence and mortality varied greatly in the 60 selected countries, and much higher incidence and mortality were observed in countries with higher HDIs, and vice versa. From 2000 to 2019, significant increases of incidence and mortality were observed for 33 countries (average annual percent changes [AAPCs], 0.24-3.82) and 18 countries (AAPCs, 0.41-2.22), respectively. A stronger increase in incidence was observed among males (AAPCs, 0.36-4.54) and individuals <50 years (AAPCs, 0.56-3.86). Notably, 15 countries showed significant decreases in both incidence (AAPCs, -0.24 to -2.19) and mortality (AAPCs, -0.84 to -2.74). A significant increase of incidence among individuals <50 years was observed in 30 countries (AAPCs, 0.28-3.62). Countries with higher incidence were more likely to have a higher prevalence of alcohol drinking, higher level of cholesterol level, higher level of unemployment, and a poorer healthcare system.CONCLUSIONS:Some high-HDI countries showed decreasing trends in CRC incidence and mortality, whereas developing countries that previously had low disease burden showed significantly increased incidence and mortality trends, especially in males and populations ≥50 years, which require targeted preventive health programs.

Colorectal cancer (CRC) is one of the most common malignancies worldwide. China, Europe and northern America account for more than half of the new CRC cases and associated deaths globally. This review summarizes the current status and temporal trends of CRC in China, Europe, and northern America. The potential primary preventive strategies and latest advances in CRC screening techniques and programs are discussed. Recently, the incidence and mortality of CRC in some European and northern American countries have decreased; conversely, CRC incidence and mortality continue to increase in China. The overall 5-year relative survival rate for CRC is similar between these regions, but there is considerable heterogeneity among European countries. Implementing population-based CRC screening programs can effectively address the growing disease burden. The effectiveness of nationwide CRC screening programs in these regions has been limited by relatively low coverage and participation rate. The deployment of state-of-the-art techniques and precise risk-adapted screening strategies incorporating effective risk prediction models and screening techniques may boost screening effectiveness. Our review provides novel foundations for the development and optimization of CRC preventive strategies.

Pancreatic cancer is a malignancy with poor prognosis and high mortality. The recent increase in pancreatic cancer incidence and mortality has resulted in an increased number of studies on its epidemiology. This comprehensive and systematic literature review summarizes the advances in the epidemiology of pancreatic cancer, including its epidemiological trends, risk factors, risk prediction models, screening modalities, and prognosis. The risk factors for pancreatic cancers can be categorized as those related to individual characteristics, lifestyle and environment, and disease status. Several prediction models for pancreatic cancer have been developed in populations with new-onset diabetes or a family history of pancreatic cancer; however, these models require further validation. Despite recent progress in pancreatic cancer screening, the quantity and quality of related studies are also unsatisfactory, especially with respect to the identification of high-risk populations and development of effective screening modality. Apart from the populations with familial genetic risk and those at a high risk of sporadic pancreatic cancer, risk factors such as new-onset diabetes may be a new direction for timely intervention. We hope this work will provide new ideas for further prevention and treatment of pancreatic cancer.

Abstract. Background:. Fecal immunochemical tests (FITs) are the most widely used non-invasive tests in colorectal cancer (CRC) screening. However, evidence about the direct comparison of the test performance of the self-administered qualitative a laboratory-based quantitative FITs in a CRC screening setting is sparse. Methods:. Based on a CRC screening trial (TARGET-C), we included 3144 pre-colonoscopy fecal samples, including 24 CRCs, 230 advanced adenomas, 622 non-advanced adenomas, and 2268 participants without significant findings at colonoscopy. Three self-administered qualitative FITs (Pupu tube) with positivity thresholds of 8.0, 14.4, or 20.8 μg hemoglobin (Hb)/g preset by the manufacturer and one laboratory-based quantitative FIT (OC-Sensor) with a positivity threshold of 20 μg Hb/g recommended by the manufacturer were tested by trained staff in the central laboratory. The diagnostic performance of the FITs for detecting colorectal neoplasms was compared in the different scenarios using the preset and adjusted thresholds (for the quantitative FIT). Results:. At the thresholds preset by the manufacturers, apart from the qualitative FIT-3, significantly higher sensitivities for detecting advanced adenoma were observed for the qualitative FIT-1 (33.9% [95% CI: 28.7–39.4%]) and qualitative FIT-2 (22.2% [95% CI: 17.7–27.2%]) compared to the quantitative FIT (11.7% [95% CI: 8.4–15.8%]), while at a cost of significantly lower specificities. However, such difference was not observed for detecting CRC. For scenarios of adjusting the positivity thresholds of the quantitative FIT to yield comparable specificity or comparable positivity rate to the three qualitative FITs accordingly, there were no significant differences in terms of sensitivity, specificity, positive/negative predictive values and positive/negative likelihood ratios for detecting CRC or advanced adenoma between the two types of FITs, which was further evidenced in ROC analysis. Conclusions:. Although the self-administered qualitative and the laboratory-based quantitative FITs had varied test performance at the positivity thresholds preset by the manufacturer, such heterogeneity could be overcome by adjusting thresholds to yield comparable specificities or positivity rates. Future CRC screening programs should select appropriate types of FITs and define the thresholds based on the targeted specificities and manageable positivity rates.

To study the clinical features of infectious mononucleosis (IM) caused by Epstein-Barr virus (EBV) mixed with Mycoplasma pneumonia (MP) or/and cytomegalovirus (CMV)infection, collected 201 hospitalized children who met the IM diagnostic criteria, the clinical manifestations, laboratory tests, complications, treatment, and outcome were compared among EBV infection alone and EBV mixed with MP or/and CMV infection. Most of the children with IM were preschoolers, more frequently occurred in boys than girls. EBV patients with MP had the longest duration of fever. When mixed pathogen infections were involved, the white blood cell count of preschool children was significantly increased, while splenomegaly was more common in older children. In the cases of EBV infection alone, abnormal liver function was positively correlated with age (P=0.044). Mixed pathogen infections were more common in children with IM, occurring in all age groups, and some clinical characteristics were related to the age of onset and the pathogen of the infection.