Endoscopic Surveillance for Premalignant Esophageal Lesions: A Community-Based Multicenter, Prospective Cohort Study.

BACKGROUND & AIMS: Mild and moderate dysplasia are major premalignant lesions of esophageal squamous cell carcinoma (ESCC); however, evidence of the progression risk in patients with these conditions is extremely limited. We aimed to assess the incidence and risk factors for advanced neoplasia in patients with mild-moderate dysplasia. METHODS: This prospective cohort study included patients with mild-moderate dysplasia from 9 regions in rural China. These patients were identified from a community-based ESCC screening program conducted between 2010 and 2016 and were offered endoscopic surveillance until December 2021. We estimated the incidence of advanced esophageal neoplasia, including severe dysplasia, carcinoma in situ, or ESCC, and identified potential risk factors using the Cox regression model. RESULTS: The 1183 patients with mild-moderate dysplasia were followed up over a period of 6.95 years. During follow-up evaluation, 88 patients progressed to advanced neoplasia (7.44%), with an incidence rate of 10.44 per 1000 person-years. The median interval from the progression of mild-moderate dysplasia to advanced neoplasia was 2.39 years (interquartile range, 1.58-4.32 y). A total of 74.47% of patients with mild-moderate dysplasia experienced regression to nondysplasia, and 18.09% showed no lesion progression. Patients with mild-moderate dysplasia who had a family history of esophageal cancer and were age 55 years and older showed 97% higher advanced neoplasia yields than all patients with mild-moderate dysplasia. CONCLUSIONS: In a country with a high incidence of ESCC, patients with mild-moderate dysplasia showed an overall risk of advanced neoplasia progression of 1.04% per year. Patients with mild-moderate dysplasia would be recommended for endoscopic surveillance during the first 2 to 3 years.

Construction and validation of a nomogram to predict the overall survival of small cell lung cancer: a multicenter retrospective study in Shandong province, China.

BACKGROUND: Patients diagnosed with small cell lung cancer (SCLC) typically experience a poor prognosis, and it is essential to predict overall survival (OS) and stratify patients based on distinct prognostic risks. METHODS: Totally 2309 SCLC patients from the hospitals in 15 cities of Shandong from 2010 - 2014 were included in this multicenter, population-based retrospective study. The data of SCLC patients during 2010-2013 and in 2014 SCLC were used for model development and validation, respectively. OS served as the primary outcome. Univariate and multivariate Cox regression were applied to identify the independent prognostic factors of SCLC, and a prognostic model was developed based on these factors. The discrimination and calibration of this model were assessed by the time-dependent C-index, time-dependent receiver operator characteristic curves (ROC), and calibration curves. Additionally, Decision Curve Analysis (DCA) curves, Net Reclassification Improvement (NRI), and Integrated Discriminant Improvement (IDI) were used to assess the enhanced clinical utility and predictive accuracy of the model compared to TNM staging systems. RESULTS: Multivariate analysis showed that region (Southern/Eastern, hazard ratio [HR] = 1.305 [1.046 - 1.629]; Western/Eastern, HR = 0.727 [0.617 - 0.856]; Northern/Eastern, HR = 0.927 [0.800 - 1.074]), sex (female/male, HR = 0.838 [0.737 - 0.952]), age (46-60/≤45, HR = 1.401 [1.104 - 1.778]; 61-75/≤45, HR = 1.500 [1.182 - 1.902]; >75/≤45, HR = 1.869 [1.382 - 2.523]), TNM stage (II/I, HR = 1.119[0.800 - 1.565]; III/I, HR = 1.478 [1.100 - 1.985]; IV/I, HR = 1.986 [1.477 - 2.670], surgery (yes/no, HR = 0.677 [0.521 - 0.881]), chemotherapy (yes/no, HR = 0.708 [0.616 - 0.813]), and radiotherapy (yes/no, HR = 0.802 [0.702 - 0.917]) were independent prognostic factors of SCLC patients and were included in the nomogram. The time-dependent AUCs of this model in the training set were 0.699, 0.683, and 0.683 for predicting 1-, 3-, and 5-year OS, and 0.698, 0.698, and 0.639 in the validation set, respectively. The predicted calibration curves aligned with the ideal curves, and the DCA curves, the IDI, and the NRI collectively demonstrated that the prognostic model had a superior net benefit than the TNM staging system. CONCLUSION: The nomogram using SCLC patients in Shandong surpassed the TNM staging system in survival prediction accuracy and enabled the stratification of patients with distinct prognostic risks based on nomogram scores.

Assessment of the compliance, influencing factors, and yielding results of liver cancer screening in a high-risk population: A cross-sectional study.

BACKGROUND: The participation and results for liver cancer screening are rarely reported. The aim of this study was to determine the participation rates and factors affecting participation rates as well as to report the detection rate for liver cancer in an organized screening program. METHODS: The organized screening program for liver cancer was conducted in 12 rural sites. The risk of developing liver cancer was initially evaluated for each participant. High-risk individuals were offered α-fetoprotein measurement and ultrasonography examination. Potential risk factors associated with the participation rate were screened by fitted generalized linear mixed logistic regression models through reporting odds ratios (ORs) with 95% CIs. RESULTS: A total of 358,662 eligible participants completed the basic surveys, and 54,745 were evaluated to be at high risk of liver cancer. Of these high-risk individuals, 40,543 accepted the screening services. Determinants of participation for screening behavior included older age, being female, being positive for hepatitis B surface antigen, having a family history of liver cancer, chronic depression, and low income. The detection rate for liver cancer was estimated to be 0.41% (95% CI, 0.35-0.48). CONCLUSIONS: This study reported several significant factors associated with the screening behaviors for liver cancer. LAY SUMMARY: Participation rate and results for liver cancer screening in rural areas are rarely reported. The determinants associated with adherence rates and early detection rate of liver cancer in an organized screening program for liver cancer were assessed. A possible positive correlation between the participation rates and the early detection rate was observed among attendees of screening. These new finds could be beneficial to increasing the participation rate of screening.

Selection of high-risk individuals for esophageal cancer screening: A prediction model of esophageal squamous cell carcinoma based on a multicenter screening cohort in rural China.

The mortality benefit of esophageal squamous cell carcinoma (ESCC) screening has been reported in several studies; however, the results of ESCC screening programs in China are suboptimal. Our study aimed to develop an ESCC risk prediction model to identify high-risk individuals for population-based esophageal cancer screening. In total, 86 745 participants enrolled in a population-based esophageal cancer screening program in rural China between 2007 and 2012 were included in the present study and followed up until December 31, 2015. Models for identifying individuals at risk of ESCC within 3 years were created using logistic regressions. The area under the receiver operating curve (AUC) was determined to estimate the model's overall performance. A total of 298 individuals were diagnosed with ESCC within 3 years after baseline. The model of ESCC included the predictors of age, sex, family history of upper gastrointestinal cancer, smoking status, alarming symptoms of retrosternal pain, back pain or neck pain, consumption of salted food and fresh fruits and disease history of peptic ulcer or esophagitis (AUC of 0.81; 95% confidence interval: 0.78-0.83). Compared to the current prescreening strategy in our program, the cut-off value of 10 in the score-based model could result in 3.11% fewer individuals subjected to endoscopies and present higher sensitivity, slightly higher specificity and lower number needed to screen. This score-based risk prediction model of ESCC based on eight epidemiological risk factors could increase the efficiency of the esophageal cancer screening program in rural China.

An initial screening strategy based on epidemiologic information in esophageal cancer screening: a prospective evaluation in a community-based cancer screening cohort in rural China.

BACKGROUND AND AIMS: In China, regional organized esophageal cancer screening programs have been implemented since 2005. However, the implementation of these screening programs is still facing some urgent challenges, especially concerning identifying high-risk individuals. This study aimed to evaluate the risk stratification potential of the current initial assessment strategy used in a mass esophageal squamous cell carcinoma (ESCC) screening program in China. METHODS: A total of 43,875 participants without a previous cancer history enrolled in a mass ESCC screening program in China from 2007 to 2010 who had initial assessment results were included in this study and were followed until December 31, 2015. Eight potential risk factors for ESCC were evaluated in the initial assessment strategy. A comprehensive evaluation of the association of the initial assessment results with ESCC risk was performed by propensity score matching and Cox regression analysis. RESULTS: During a median follow-up of 5.5 years, 272 individuals developed ESCC. The high-risk population assessed at baseline had a higher risk of ESCC than the non-high-risk population, with a hazard ratio (HR) of 3.11 (95% confidence interval (CI), 2.33-4.14) after adjustment for sex, age, education level, income level, and body mass index. In addition, the initial assessment results of the high-risk population were significantly associated with the risk of all esophageal cancers (HR, 3.30; 95% CI, 2.51-4.33) and upper gastrointestinal cancers (HR, 3.03; 95% CI, 2.43-3.76). CONCLUSIONS: The initial screening tool in a mass ESCC screening program in China, consisting of 8 accessible variables in epidemiologic surveys, could be helpful for the selection of asymptomatic individuals for priority ESCC screening.

Long-term effectiveness of one-time endoscopic screening for esophageal cancer: A community-based study in rural China.

BACKGROUND: Evidence is required to quantify the population-level effects of endoscopic screening for esophageal squamous cell carcinoma (ESCC). The objective of this study was to evaluate the long-term effectiveness of 1-time endoscopic ESCC screening in a Chinese rural population. METHODS: This community-based cohort study was based on an existing esophageal cancer screening program in Feicheng City, China. The screening group consisted of all permanent residents aged 40 to 69 years in 17 villages who were screened during 2006 through 2009, and the control group consisted of residents in another 43 villages who were not yet covered by the screening program. Residents in the remaining 511 villages were defined as the total population control. The cumulative incidence and mortality of ESCC and the observed and expected numbers of ESCC cases and deaths during the follow-up period (2010-2018) were calculated and compared. RESULTS: After a 9-year follow-up, the screening group (n = 8460) revealed reductions of 20% (relative risk, 0.80; 95% CI, 0.66-0.97) and 32% (relative risk, 0.68; 95% CI, 0.52-0.89) in ESCC cumulative incidence and mortality, respectively, compared with the control group (n = 20,468). Endoscopic screening prevented 0.41% of the population (attributable risk, 0.41%; 95% CI, 0.07%-0.75%) from ESCC occurrence and 0.38% (attributable risk, 0.38%; 95% CI, 0.14%-0.62%) from ESCC-related death. In the screening group, reductions of 43% (standardized incidence ratio, 0.57; 95% CI, 0.48-0.67) and 45% (standardized mortality ratio, 0.55; 95% CI, 0.44-0.69) were found in the observed cumulative cases and deaths, respectively, compared with the expected cases and deaths. CONCLUSIONS: One-time endoscopic screening was associated with a significant and consistent reduction in ESCC incidence and mortality among individuals aged 40 to 69 years in high-risk areas.

Association of cancer awareness levels with the risk of cancer in rural China: A population-based cohort study.

BACKGROUND: Evidence of the effects of cancer prevention knowledge on the risk of developing cancer remains scarce. The objective of this study was to prospectively examine the association of cancer prevention awareness levels with cancer risk in a population-based cancer screening cohort in China. METHODS: This prospective cohort study included 164,341 participants aged 40 to 69 years with no history of cancer and with available information on cancer prevention core knowledge in the Esophageal, Stomach, and Liver Cancer Screening Program. Participants were recruited from 18 rural regions across 4 provinces in China from 2007 to 2014 and were followed until December 31, 2015. The core knowledge of cancer prevention content included 9 items, with a total score ranging from 0 to 100. Cox proportional hazards regression models and restricted cubic spline analysis were used to estimate hazard ratios and 95% CIs. RESULTS: High cancer prevention knowledge scores were inversely associated with the overall risk of cancer (group 4 vs group 1: hazard ratio, 0.669; 95% CI, 0.576-0.776). Subgroup analysis showed that this inverse association could be observed in women, participants with lower educational or income levels, and those without a family history of cancer. Restricted cubic spline analysis exhibited a nonlinear (L-shaped) relation between cancer knowledge scores and cancer risk (overall P < .0001; nonlinear P = .0141). CONCLUSIONS: The main finding of this prospective study was that higher levels of cancer prevention awareness could be associated with a relative reduction in the risk of developing cancer.

Pd-Catalyzed cascade cyclization of o-alkynylanilines via C-H/C-N bond cleavage leading to dibenzo[a,c]carbazoles.

A new and efficient Pd-catalyzed cascade cyclization of biaryl-tethered o-alkynylanilines for the formation of dibenzo[a,c]carbazole derivatives has been reported. The use of the alkyl-substituted tertiary anilines together with the combination of the PdCl2 catalyst with the MnO2 oxidant and PivOH is vital for giving rise to 5-endo cyclization, C-N bond cleavage, and C-H bond activation in a cascade manner to produce the corresponding products with structural diversity.

[Results of the endoscopic screening program of esophageal and gastric cardia cancers using iodine staining in Feicheng, Shandong Province, from 2006 to 2012].

OBJECTIVE: To investigate the prevalence of esophageal and gastric cardia cancer and various precancerous lesions in high-risk rural areas. METHODS: Random cluster sampling method was used to select people aged 40-69 years of some natural villages as screening objects in Feicheng, Shangdong province, from 2006 to 2012. The screening program was conducted by endoscopy with iodine staining and indicative biopsy followed by pathological examination. RESULTS: A total of 24 759 subjects were screened during 2006-2012 years. The positive detection rates of esophagus and gastric cardia cancers were 1.37% and 0.42%, respectively, the early diagnosis rates were 84.71% and 65.05%, and the treatment rates were 92.65% and 92.23%, respectively. The detection rates of all lesions in males were significantly higher than those in females (P < 0.05), and were gradually increased with age (P < 0.05). The time trend analysis showed that detection rates of all lesions in the two sites showed no significant changes during this period, and the detection rates of esophageal lesions were higher than those of gastric cardia. CONCLUSIONS: There are considerable numbers of patients with precancerous lesions in the general population from the high risk areas. Men and the elderly are the key populations calling for cancer control programs. Endoscopy using iodine staining is an effective method to increase the detection rate of precancerous lesions and cancers. The root of mucosal fold in gastric cardia must be carefully observed so as to increase the detection rate of early gastric cardia lesions.

[Analysis of mortality and years of life lost of malignant tumors among inhabitants in rural area of Feicheng city from 2000 to 2010].

OBJECTIVE: To analyze the mortality trends and disease burden of malignant tumors in rural area of Feicheng city from 2000 to 2010, and to provide basic information for the prevention and treatment of malignant tumors in this area. METHODS: The data of cancer mortality from 2000 to 2010 from Feicheng Cancer Registry database were checked. Mortality rate, standardized mortality rate, potential years of life Iost (PYLL), standardized potential years of life lost (SPYLL), average years of life lost (AYLL) and other indexes were calculated and analyzed. The trend of the standardized rates transformed by the natural logarithm over time was assessed by Prais-Winsten regression method in which the errors was assumed to follow a first-order autoregressive process. STATA 12.0 was used to analyze the data. RESULTS: In average, the crude mortality rate was 199.67 per 100 000 (264.69 per 100 000 in males and 137.24 per 100 000 in females), and the standardized mortality rate was 157.00 per 100 000 (200.49 per 100 000 in males and 101.31 per 100 000 in females). There were no significant changes in the trends of all standardized rates. For males, the mortality rates of lung and colorectal cancers increased significantly, and for females, the rates of lung and breast cancers had increased trend while the rate of esophageal cancer showed a downward trend. There were no statistically significant changes in other main malignant tumors. During 2000 to 2010, the PYLL of malignant tumors in Feicheng was 183 685.0 person-years, and PYLL rate was 23.3 per 1000. The SPYLL was 153 091.0 person-years, SPYLL rate was 19.4 per 1000, and AYLL was 14.8 years. CONCLUSIONS: There are no obvious changes in the trends of standardized mortality rates in rural area of Feicheng over the past 11 years. For males, the mortality of lung cancer and colorectal cancer is increasing, and for females, the rates of lung and breast cancers have an increasing trend while the rate of esophageal cancer shows a decreasing trend. The prevention and control of digestive malignant tumors, lung cancer and breast cancer are getting seriously important and should be the focal point in this issue.

Long-term esophageal cancer risk and distinct surveillance intervals after a single endoscopy screening: a multicentre population-based cohort study.

Background: Endoscopy surveillance is recommended for mild-moderate dysplasia and negative endoscopy findings every 3 years and 5 years, respectively, but evidence is limited. This study aimed to assess long-term esophageal cancer (EC) incidence and mortality after a single endoscopy screening. Methods: We included individuals at high risk of EC aged 40-69 years who underwent endoscopy screening in 2007-2012 at six centres in rural China and had a baseline diagnosis of negative endoscopy findings, mild dysplasia, or moderate dysplasia. Participants were followed up for EC incidence and mortality. Cumulative incidence and mortality rates of EC were estimated by Kaplan-Meier analyses. Cox regression models were used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between baseline endoscopy diagnosis and the risk of EC incidence and mortality. EC incidence and mortality after a single endoscopy screening were compared with those of the population in rural China by the standardized incidence ratio (SIR) and standardized mortality ratio (SMR). Findings: A total of 42,827 participants (40,977 with negative endoscopy findings, 1562 with mild dysplasia, and 288 with moderate dysplasia) were included; 268 EC cases and 128 EC deaths were identified during a median follow-up of 10.62 years. The cumulative EC incidence at 10 years was 0.45% (0.38-0.52) in the group with negative endoscopy findings, 2.39% (1.62-3.16) in the mild dysplasia group, and 8.90% (5.57-12.24) in the moderate dysplasia group, and the cumulative EC mortality at 10 years was 0.23% (0.18-0.27), 0.96% (0.46-1.46), and 2.50% (0.67-4.33), respectively. Compared with individuals with negative endoscopy findings, the HRs for EC incidence and mortality in the mild dysplasia group were 3.52 (2.49-4.97) and 2.43 (1.41-4.19), and those in the moderate dysplasia group were 13.18 (8.78-19.76) and 6.46 (3.13-13.29), respectively. The SIR was 0.53 (0.40-0.70) for the group with negative endoscopy findings, 1.95 (1.69-2.24) for the mild dysplasia group, and 6.75 (6.25-7.28) for the moderate dysplasia group, with the SMRs of 0.43 (0.31-0.58), 1.07 (0.88-1.29) and 2.67 (2.36-3.01), respectively. Interpretation: Individuals with negative endoscopy findings after a single endoscopy screening had a lower EC risk than the general population for up to 10.62 years, while those with mild-moderate dysplasia had an elevated risk. Our results support endoscopy surveillance for mild-moderate dysplasia every 3 years and suggest extending the interval to 10 years after a negative endoscopy finding. Funding: National Key R&D Programme of China, Special Project of Beijing-Tianjin-Hebei Basic Research Cooperation, and Sanming Project of Medicine in Shenzhen.

Long-term Incidence Rates of Esophageal Squamous Cell Carcinoma in Chinese Patients With Low-grade Intraepithelial Neoplasia and Association of Surveillance Endoscopy With Incidence.

Importance: Surveillance endoscopy is recommended for patients with low-grade intraepithelial neoplasia (LGIN); high-quality evidence about the use of surveillance endoscopy and esophageal squamous cell carcinoma (ESCC) incidence in patients with LGIN is important but limited. Objective: To estimate long-term ESCC incidence rates in patients with LGIN and the association between surveillance endoscopy and ESCC incidence. Design, Setting, and Participants: This community-based, multicenter, prospective cohort study in 9 regions in rural China included patients with LGIN diagnosed by endoscopic screening between July 1, 2007, and December 31, 2016; all participants were followed up until December 31, 2021. Main Outcomes and Measures: The primary outcome was ESCC incidence. The ESCC standardized incidence ratio (SIR) was estimated using sex- and age-specific incidence in the general population of rural China in 2010 and hazard ratios (HRs) and 95% CIs were calculated using Cox proportional hazards models. Results: A total of 3258 patients with LGIN were included; 1772 (54.39%) were men, with a mean (SD) age of 58.21 (6.97) years. Among them, 1378 patients (42.30%) underwent at least 1 surveillance endoscopy (surveillance group) and 1880 (57.70%) did not undergo any surveillance endoscopy (nonsurveillance group). During the follow-up period (median, 7.96 years; IQR, 6.08-10.54 years), 170 ESCC cases were diagnosed, with a cumulative incidence of 6.28 per 1000 person-years. A higher incidence of ESCC (incidence rate, 7.07 per 1000 person-years) was observed in the nonsurveillance group than in the surveillance group (incidence rate, 5.14 per 1000 person-years). Patients with LGIN in the surveillance group had a lower SIR (SIR, 4.07; 95% CI, 1.13-10.34) than those in the nonsurveillance group (SIR, 5.65; 95% CI, 2.00-12.58); however, patients with LGIN in both groups had a higher risk of ESCC than the general population. Patients in the surveillance group had a 31% decreased risk of ESCC incidence (HR, 0.69; 95% CI, 0.50-0.95) compared with those in the nonsurveillance group, after adjusting for baseline risk factors. Conclusions and Relevance: In this prospective cohort study, patients with LGIN had a higher risk of developing ESCC than the general population, and endoscopic surveillance was associated with a decrease in ESCC incidence in these patients.

Health-related quality of life and utility scores of patients with breast neoplasms in China: A multicenter cross-sectional survey.

BACKGROUND: Health-related quality of life and utility scores of patients with breast cancer and precancerous lesions are sparse in China. This study aimed to derive utility scores of patients with breast cancer and precancer in China. MATERIAL AND METHODS: An interviewer-administered cross-sectional survey was conducted in 12 provinces across China from 2013 to 2014. The three-level EuroQol-5-Dimension instrument was used to evaluate quality of life, and utility scores were generated using the Chinese value set. Univariate and multivariate analyses were performed to explore the determinants of utility scores. RESULTS: In total, 2626 breast cancer and 471 precancer patients were included. Mean age was 49.1 for breast cancer and 41.4 years for precancer (p < 0.001). Among the five dimensions, pain/discomfort was the most reported problem, 53.9% in breast cancer and 29.3% in precancer patients. Mean (95% CI) utility scores for breast cancer and precancer patients were estimated as 0.887 (0.875-0.899) and 0.781 (0.774-0.788), and the scores of breast cancer at stage-I, stage-II, stage-III and stage-IV were 0.789 (0.774-0.805), 0.793 (0.783-0.802), 0.774 (0.759-0.788) and 0.686 (0.654-0.717), respectively. Mean (95% CI) visual analogue scale scores for breast cancer and precancer were 75.6 (74.0-77.3) and 72.8 (72.3-73.3). Multiple regression showed advanced clinical stage, lower educational level, lower household income, surgery treatment, and undergoing treatment were independently associated with lower utility scores for breast cancer patients. CONCLUSION: The utility scores deteriorate with the severity of breast neoplasms. Detailed utility scores of breast cancer and precancer are fundamental for further cost-utility analysis in China.

Preliminary effectiveness of breast cancer screening among 1.22 million Chinese females and different cancer patterns between urban and rural women.

To determine the preliminary effectiveness of breast cancer screening among Chinese females, 1226714 women aged 35-69 years first received clinical breast examinations. Urban women with suspected cancer received mammography followed by breast ultrasound (BUS), while rural suspected women underwent BUS followed by mammography. After one-year follow-up, 223 and 431 breast cancers were detected among urban and rural women (respectively), with overall detection rates of 0.56/1000 and 0.52/1000. Higher detection rates were significantly associated with older age at screening for both urban and rural women; additionally, urban women were at significantly higher risk if they had no job, no insurance, or were obese; additional risk factors specific to rural women included Han nationality, higher income, being unmarried, and having a family history of cancer (all P values < 0.05). Among screening-detected breast cancers in urban vs. rural women, 46.2% and 38.8% (respectively) were early stage, 62.5% and 66.3% were ≤2 centimeters, 38.0% and 47.3% included lymph-node involvement, and 14.0% and 6.0% were identified as carcinoma in situ. All abovementioned cancer characteristics were significantly better than clinic-detected cancers (all P values < 0.001). In conclusion, several important differences were found between urban and rural women in screening effectiveness and patterns of cancer distribution.