Esophageal Histological Precursor Lesions and Subsequent 8.5-Year Cancer Risk in a Population-Based Prospective Study in China.

INTRODUCTION: Data on the associations between esophageal histological lesions and risk of esophageal squamous cell carcinoma (ESCC) in general populations are limited. We aimed to investigate these associations in a large Chinese general population to inform future Chinese ESCC screening guidelines. METHODS: We performed endoscopic screening of 21,111 participants aged 40-69 years from 3 high-risk areas of China in 2005-2009, and followed the cohort through 2016. Cumulative incidence and mortality rates of ESCC were calculated by baseline histological diagnosis, and hazard ratios of ESCC, overall and by age and sex, were assessed using the Cox proportional hazards models. RESULTS: We identified 143 new ESCC cases (0.68%) and 62 ESCC deaths (0.29%) during a median follow-up of 8.5 years. Increasing grades of squamous dysplasia were associated with the increasing risk of ESCC incidence and mortality. The cumulative ESCC incidence rates for severe dysplasia/carcinoma in situ, moderate dysplasia (MD), and mild dysplasia were 15.5%, 4.5%, and 1.4%, respectively. Older individuals (50-69 years) had 3.1 times higher ESCC incidence than younger individuals (40-49 years), and men had 2.4 times higher ESCC incidence than women. DISCUSSION: This study confirmed that increasing grades of squamous dysplasia are associated with increasing risk of ESCC and that severe dysplasia and carcinoma in situ require clinical treatment. This study suggests that in high-risk areas of China, patients with endoscopically worrisome MD should also receive therapy, the first screening can be postponed to 50 years, and endoscopic surveillance intervals for unremarkable MD and mild dysplasia can be lengthened to 3 and 5 years, respectively.

Endoscopy screening effect on stage distributions of esophageal cancer: A cluster randomized cohort study in China.

Efficacy of endoscopic screening for esophageal cancer is not sufficiently definitive and lacks randomized controlled trial evidence. The present study proved short-term screening efficacy through describing and comparing disease stage distributions of intervention and control populations. Villages from Linzhou and Cixian were cluster randomly allocated to the intervention or to the control group and the target population of 52 729 and 43 068 individuals was 40-69 years old, respectively, and the actual enrolled numbers were 18 316 and 21 178, respectively. TNM stage information and study-defined stage information of esophageal cases from 2012 to 2016 were collected. Stage distributions were compared between the intervention and control groups in the total target population, as well as in the subgroup populations in terms of enrolment and before or after intervention. There were a total of 199 and 141 esophageal cancer cases in the intervention and control groups, respectively. For the target population, distributions of TNM stage were borderline significant between the two groups after intervention (P = .093). However, subgroup analysis of the enrolled population during the after-intervention period had statistical significance for both TNM and study-defined stage. Natural TNM stage distributions were approximately 32%, 41%, 24% and 3% for stages I to IV vs 71%, 19%, 7% and 3% in the intervention population. The natural study-defined stage distributions from early, middle to advanced stages were approximately 18%, 49% and 33% vs 59%, 33% and 8%. Early-stage esophageal cancer cases accounted for a higher proportion after endoscopy screening, and the efficacy in the target population depends on the intervention compliance.

Satisfaction and its determinants of rural upper gastrointestinal cancer screening in China: a preliminary cross-sectional study.

OBJECTIVES: To assess participants' satisfaction with and predictors of upper gastrointestinal cancer screening in rural areas. DESIGN: Cross-sectional study. SETTING: Ten screening centres in seven cities across five provinces in China. PARTICIPANTS: Of the 452 participants screened during the survey period, 438 completed the survey (response rate: 96.90%). PRIMARY OUTCOME MEASURES: Screening satisfaction was the primary outcome and it was assessed using the Patient Satisfaction Questionnaire-18. Ordinal logistic regression analysis was used to analyse the predictors of satisfaction. RESULTS: The percentages of satisfaction with the General Satisfaction, Technical Quality, Interpersonal Manner, Communication, Financial Aspects, Time Spent With Doctor, and Convenience and Accessibility dimensions were 95.89%, 79.68%, 88.36%, 83.56%, 75.11%, 82.19% and 66.44%, respectively. Education (OR 0.25, 95% CI 0.07 to 0.90), health self-assessment (OR 15.29, 95% CI 2.86 to 81.78) and family history of cancer (OR 4.20, 95% CI 1.29 to 13.71) were associated with General Satisfaction. Residence (OR 4.31, 95% CI 1.89 to 9.81) was associated with Technical Quality. Occupation (OR 0.27, 95% CI 0.08 to 0.88), health self-assessment (OR 11.30, 95% CI 3.94 to 32.43), screening purpose (OR 0.18, 95% CI 0.03 to 0.92) and distance from the screening centre (OR 4.59, 95% CI 1.35 to 15.61) were associated with interpersonal manner. Gender (OR 1.85, 95% CI 1.02 to 3.34), residence (OR 3.23, 95% CI 1.23 to 8.53) and endoscopy in the previous year (OR 2.79, 95% CI 1.13 to 6.90) were associated with Communication. Body mass index (BMI; OR 5.06, 95% CI 1.40 to 18.25) and health self-assessment (OR 2.09, 95% CI 1.12 to 3.88) were associated with financial aspects. Gender (OR 1.90, 95% CI 1.07 to 3.38), residence (OR 3.19, 95% CI 1.30 to 7.79), BMI (OR 5.26, 95% CI 1.14 to 24.34) and health self-assessment (OR 2.14, 95% CI 1.06 to 4.34) were associated with time spent with doctor. Gender (OR 1.64, 95% CI 1.04 to 2.60) and residence (OR 3.17, 95% CI 1.46 to 6.88) were associated with convenience and accessibility. CONCLUSION: There was heterogeneity across the dimensions of satisfaction with rural upper gastrointestinal cancer screening. Project manager should prioritise improving the aspects related to the convenience and accessibility dimension. Furthermore, to improve the efficiency of potential interventions, the predictors of the various dimensions should be considered.

Esophageal Thermal Exposure to Hot Beverages: A Comparison of Metrics to Discriminate Distinct Consumption Habits.

BACKGROUND: Hot beverage consumption is a probable risk factor for esophageal squamous cell carcinoma (ESCC). No standardized exposure assessment protocol exists. METHODS: To compare how alternative metrics discriminate distinct drinking habits, we measured sip temperatures and sizes in an international group of hot beverage drinkers in France (n = 20) and hot porridge consumers (n = 52) in a high ESCC incidence region of China. Building on the knowledge that sip size and temperature affect intraesophageal liquid temperature (IELT), IELTs were predicted by modeling existing data, and compared with first sip temperature and, across all sips, mean temperature and sip-weighted mean temperature. RESULTS: Two contrasting exposure characteristics were observed. Compared with the international group, Chinese porridge consumers took larger first sips [mean difference +17 g; 95% confidence interval (CI), 13.3-20.7] of hotter (+9.5°C; 95% CI, 6.2-12.7) liquid, and their mean sip size did not vary greatly across sips, but the former groups increased in size as temperature decreased. This resulted in higher predicted IELTs (mean 61°C vs. 42.4°C) and sip-weighted temperatures (76.9°C vs. 56°C) in Chinese porridge consumers, and compared with first sip and mean temperature, these two metrics separated the groups to a greater extent. CONCLUSIONS: Distinguishing thermal exposure characteristics between these groups was greatly enhanced by measuring sip sizes. Temperature at first sip alone is suboptimal for assessing human exposure to hot foods and beverages, and future studies should include sip size measurements in exposure assessment protocols. IMPACT: This study provides a logistically feasible framework for assessing human exposure to hot beverages.

Application of Computer-Aided Tongue Inspection for Preliminary Screening of Esophageal Cancer.

OBJECTIVE: To differentiate patients with esophageal cancer or premalignant lesions from the high-risk population for preliminary screening of esophageal cancer using a feature index determined by a computer-aided tongue information acquisition and processing system (DS01-B). METHODS: Totally, 213 patients diagnosed with esophageal cancer or premalignant lesions and 2,840 normal subjects were collected including primarily screened and reexamined, all of them were confirmed with histological examinations. Their tongue color space values and manifestation features were extracted by DS01-B and analyzed. Firstly, the analysis of variance was performed to differentiate normal subjects from patients with esophageal cancer and premalignant lesions. Secondly, the logistic regression was conducted using 10 features and gender, age to get a predictive equation of the possibility of esophageal cancer or premalignant lesions. Lastly, the equation was tested by subjects undergoing primary screening. RESULTS: Saturation (S) values in the HSV color space showed significant differences between patients with esophageal cancer and normal subjects or those with mild atypical hyperplasia (P<0.05); blue-to-yellow (b) values in the Lab color space showed significant differences between patients with esophageal cancer or premalignant lesions and normal subjects (P<0.05). Logistic regression analysis showed that the computer-aided tongue inspection approach had an accuracy of 72.3% (2008/2776) in identifying patients with esophageal cancer or premalignant lesions for preliminary screening in high-risk population. CONCLUSION: Computer-aided tongue inspection, with descriptive and quantitative profile as described in this study, could be applied as a cost- and timeefficient, non-invasive approach for preliminary screening of esophageal cancer in high-risk population.

Upper gastrointestinal cancer burden in Hebei Province, China: A population-based study.

AIM: To investigate the incidence and mortality rates of upper gastrointestinal cancer (UGIC) in Hebei Province, China, and to identify high-risk populations to improve UGIC prevention and control. METHODS: Data for UGIC patients were collected from 21 population-based cancer registries covering 15.25% of the population in Hebei Province. Mortality data were extracted from three national retrospective death surveys (1973-1975, 1990-1992 and 2004-2005). The data were stratified by 5-year age groups, gender and area (high-risk/non-high-risk areas) for analysis. The age-period-cohort and grey system model were used. RESULTS: The crude incidence rate of UGIC was 55.47/100000, and the adjusted rate (Segi's population) was 44.90/100000. Males in rural areas had the highest incidence rate (world age-standardized rate = 87.89/100000). The crude mortality rate of UGIC displayed a decreasing trend in Hebei Province from the 1970s to 2013, and the adjusted rate decreased by 43.81% from the 1970s (58.07/100000) to 2013 (32.63/100000). The mortality rate declined more significantly in the high-risk areas (57.26%) than in the non-high-risk areas (55.02%) from the 1970s to 2013. The median age at diagnosis of UGIC was 65.06 years in 2013. There was a notable delay in the median age at death from the 1970s (66.15 years) to 2013 (70.39 years), especially in the high-risk areas. In Cixian, the total trend of the cohort effect declined, and people aged 65-69 years were a population at relatively high risk for UGIC. We predicted that the crude mortality rates of UGIC in Cixian and Shexian would decrease to 98.80 and 133.99 per 100000 in 2018, respectively. CONCLUSION: UGIC was the major cause of cancer death in Hebei Province, and males in rural areas were a high-risk population. We should strengthen early detection and treatment of UGIC in this population.

Age scope of high-risk population for esophageal cancer in Ci county.

AIM: To define the age scope of high-risk population for esophageal cancer (EC) in Ci county. METHODS: The results of endoscopic examination of 2 013 subjects, cytological screening of 16 763 persons and records of 9 265 patients with EC were analyzed by Ridit methods, the standard age group was 45-49 year group. RESULTS: The average age of patients with moderate esophageal epithelium dysplasia by endoscopic examination was 53.5 years, of severe esophageal epithelium dysplasia, 51.4 years, early EC, 55.6 years. The average age of stage one severe epithelium dysplasia (SEEDI) by cytological screening was 51.2 years, of stage two severe epithelium esophageal dysplasia (SEED II) 51.6 years, of advanced EC 61.7 years. In the group of 40-year olds, the value of Ridit by pathological diagnosis was 0.46, 95% CI, 0.45-0.47, that by cytological diagnosis was 0.45, 95% CI, 0.43-0.47. As the age increased at five-year intervals, the value of Ridit increased significantly. CONCLUSION: In Ci county of a high incidence area of EC, the age definition of high-risk population should be above 45 years.

Decrease in the esophageal cancer incidence rate in mountainous but not level parts of Cixian County, China, over 29 years.

BACKGROUND: Cixian county has one of the highest incidence rates of esophageal cancer (EC) in China, as well as the world. In 1974, the Cixian population-based cancer registry system was established, so that there is now information on esophageal cancer cases over almost 30 years. METHODS: Data from Cixian Cancer Registry were checked and analyzed using SPSS 11.5. RESULTS: From 1974 to 2002, a total of 18,471 new esophageal cancer cases were registered in Cixian, 11,068 in males and 7,403 in females. The age standardized incidence rate (ASR) for males was 208.77 per 100,000, while for females it was 120.47 per 100,000. There was a clear trend for decrease overall in the incidence rate of esophageal cancer over the 29 years (X(2)=19.94, P<0.001). As to the geographic distribution, the incidence rate in mountainous and hilly areas showed a significant decline (X(2) = 195.00 and X(2) = 46.08, respectively, both P X(2)0.001). Data for esophageal cancer incidence in level land areas in contrast were relatively steadily, with increase in recent years. CONCLUSION: Esophageal cancer has decreased in Cixian county during the last 29 years, but this is due to change in mountainous and hilly areas. Compared to other regions in the world, Cixian county still has a very high incidence of ECs.

An analysis of esophageal cancer incidence in Cixian county from 1974 to 1996.

AIM: To describe the incidence of esophageal cancer (EC) in Cixian, a county of Hebei province during 1974-1996. We analyzed the sex and age characteristics as well as the geographic distribution of EC, in order to determine the impact so that methods of preventing and controlling EC in Cixian can be put in place. METHODS: Since the early 1970s, the cancer registry system has been established, which collects the cancer incidence in Cixian county. The malignant tumors were coded according to International Classification of Disease IX (ICD-9). All the data were checked and analyzed using EPIINFO. RESULTS: The trend of the incidence rate of EC from 1974 to 1996 had declined, (229.9/100 000 vs 178.5/100 000, Odds ratio=1.47, 95 % CI:1.32-1.63, chi(2)=52.89. trend chi(2)=26.54, P<0.001). The incidence rate of males declined significantly (281.81/100 000 vs 157.96/100 000, Odds ratio=1.61, 95 % CI: 1.41-1.84, chi(2)=47.85. Trend chi(2)=44.86, P<0.001), whereas, the females remained steady (157.96/100 000 vs 133.41/100 000, odds ratio=1.28, 95 % CI:1.17-1.49, chi(2)=9.26. trend chi(2)=2.69, P>0.05). Male average annual incidence rate was 142.80/100 000 and the female's was 95.18/100 000. The sex ratio (males to females) was 1.50:1. The incidence rate was increasing along with the age. As to the geographic distribution, the incidence rate in mountainous areas and hilly areas showed a significantly declining trend (mountainous areas, trend chi(2)=149.93, P<0.001; hilly areas, trend chi(2)=42.70, P<0.001). The incidence rate of EC in plain areas had increased (trend chi(2)=22.39, P<0.001). CONCLUSION: The incidence rate of EC in Cixian county shows a trend and has declined after two decades, especially in mountainous area. But compared to other regions in the world, Cixian county still had a high incidence rate of EC.

Evaluation of routine biopsies in endoscopic screening for esophagogastric junction cancer.

AIM: To explore whether routine biopsies at the high incidence spot of esophagogastric junction (EGJ) cancer are justified in endoscopic screening. METHODS: This was a multicenter population-based study conducted in eight high-risk areas in China. A total of 37396 participants underwent endoscopic examination. Biopsies were obtained from visible mucosal abnormalities or from normal-appearing mucosa at the high incidence spot of esophagogastric junction cancer when no abnormality was detected. Specimens showing high-grade intraepithelial neoplasia (HIN) or higher grade lesions were deemed as pathologically "positive". The ratios of positive pathologic diagnosis between participants with abnormal and normal-appearing mucosa were compared using the Pearson χ(2) test. Odds ratios and 95% confidence intervals, adjusted for potential confounders, were calculated using logistic regression. RESULTS: A total of 37520 individuals participated in this study and 37396 (99.7%) participants had full information and were suitable for analysis. During endoscopic examinations, 9.11% (3405/37396) participants were found to have visible mucosal lesions. Of the participants who had normal-appearing mucosa at the EGJ, only 0.28% (94/33991) were diagnosed with HIN or higher grade lesions, whereas 6.05% (206/3405) of participants with abnormalities at the EGJ had a positive pathologic result. After controlling for other variables, visible abnormal mucosa detected under endoscopy strongly predicted a positive pathologic result (OR = 32.51, 95%CI: 23.96-44.09). The proportion of participants with "positive" pathologic diagnoses increased as the total number of endoscopic examinations performed by the doctors increased (< 5000 cases vs 5000-10000 cases vs > 10000 cases, Z = -2.7207, P = 0.0065, Cochran Armiger trend test). The same trend was found between the proportion of participants with positive pathologic diagnoses and the total number of years the doctors performed endoscopy (< 5 years vs 5-10 years vs > 10 years, Z = -10.3222, P < 0.001, Cochran Armiger trend test). CONCLUSION: Additional routine biopsies from the high incidence spot of EGJ cancer are of limited value and are unjustified.

Estimating the costs of esophageal cancer screening, early diagnosis and treatment in three high risk areas in China.

BACKGROUND: The incidence and mortality of esophageal cancer (EC) in some rural areas with poor health resources in China are the highest around the world. In these areas, screening programs for EC are conducted for prevention and control. However, costs associated with esophageal cancer screening have not been characterized in detail. This study is aimed to estimate the screening, early diagnosis and treatment costs of EC using micro-costing methods, which could provide basic cost inputs for further systematic health economic evaluation. MATERIALS AND METHODS: Micro-costing methods were adopted to collect data on quantity and unit cost of used resources. Data was obtained from face-to-face interview with medical staff, local hospitals' database, and experts' input. We used 80% capacity utilization and 3% discount rate to annualize capital investments, and all costs were adjusted to year 2008 using the gross domestic production deflator, and then converted from Chinese currency unit to international dollars (I$) using purchasing power parity. RESULTS: Screening costs per case were around I$60. For severe dysplasia, carcinoma in situ and intramucosal carcinoma, the costs per capita of endoscopic mucosal resection were I$1292~I$1620, and around I$450 for argon plasma coagulation. For submucosal carcinoma (T1N0M0), and invasive carcinoma treated by esophagectomy, the treatment costs ranged from I$1485 to I$2171. The costs of treatment of invasive carcinoma were: I$497~I$685.2 for radiotherapy; I$4652~I$7966.15 for chemotherapy; I$1928~I$2805 for combination of esophagectomy and radiotherapy; I$6632~I$8082 for esophagectomy, radiotherapy and chemotherapy in combination. CONCLUSION: The cost analysis found screening, early diagnosis and treatment for EC could provide great cost savings. The results provide important information for further health economic evaluation, and to help the local policy makers on updating such screening program in high risk areas in China.

Trends in incidence of esophageal and gastric cardia cancer in high-risk areas in China.

Incidence rates have risen for gastric cardia adenocarcinoma, whereas rates have remained stable for esophageal squamous cell carcinoma in many western countries. The aim of this study was to describe and analyze trends in incidence rates for esophageal cancer and gastric cardia cancer in Cixian county, which is one of the high-risk areas for esophageal cancer in China as well as in the world. The data were obtained from the Cixian Cancer Registry, which is a population-based registry. All the data were checked and analyzed using SPSS 11.5. Between the years 1988 and 2003 there were 11,183 cases of esophageal cancer in the county. The age-standardized incidence rate was 168.55 per 100,000. In 1988, the age-standardized incidence rate for male patients was 250.76/100,000; it declined to 160.05/100,000 in 2003, representing a decrease of 36.2%. The age-standardized incidence rate for female patients was 153.86/100,000 in 1988; it declined to 82.55/100,000 in 2003, showing a decrease of 46.3%. A slight decreasing trend was observed during the period, with a yearly decrease of 3.61% in male patients and 3.39% in female patients. For gastric cardia cancer, there were 1654 cases from 1988 to 2003. The age-standardized incidence rate was 25.58 per 100,000. The age-standardized incidence rate for male patients was 13.75/100,000 in 1988; it increased to 28.55/100,000 in 2003, with a yearly increase of 7.65%. The age-standardized incidence rate for female patients was 7.12/100,000 in 1988; it increased to 12.91/100,000, with a yearly increase of 5.44%. A statistically significant increasing trend of gastric cardia cancer was observed during the study period. Cixian county is a geographical region with a very high incidence of esophageal cancer and cardia cancer. The trend in the incidence rates of esophageal cancer had decreased slightly; on the other hand, gastric cardia cancer showed a significantly increased trend in the last 16 years. Detailed epidemiological analyses of demographic trends and risk factors will help to guide future cancer control strategies.

[Study on the esophageal cancer incidence and mortality rate from 1974-2002 in Cixian, China].

OBJECTIVE: To describe the incidence and mortality rates of esophageal cancer from 1974-2002 in Cixian county of Hebei province. Basic information on comparative geographical, epidemiological, and clinical research was collected. METHODS: In early 1970s, cancer registry system in Cixian was established, collecting information on all the esophageal cancer cases in Cixian. Data was checked manually, then computerized, coded and analyzed using the software--SPSS 11.5. RESULTS: From 1974 to 2002, there were 18 471 esophageal cancer cases in Cixian, with 11 068 males and 7403 females, respectively. The age standardized incidence rate (ASR) for males was 208.77 per 100,000, while 120.47 per 100,000 for females. The trend of incidence rate of esophageal cancer had decreased during the 29 years from 1974 to 2002 (trend chi(2) = 19.94, P < 0.001). From 25 years of age onward, the incidence rates of the lower age groups declined with the increase of age. As for geographic distribution, the incidence rate in mountainous areas and hilly areas showed a significant declining trend in mountainous areas, chi(2) = 195.00, P < 0.001; hilly areas, chi(2) = 46.08, P < 0.001. The esophageal cancer incidence in plain areas remained steady, but had a slight increase in recent years. From 1969 to 2002, there were 18,736 cases died of esophageal cancer with 11 598 males and 7138 females. The ASR for male was 127.17 per 100,000 and 101.57 per 100,000 for female. Compared with the year 1969, the mortality rate of esophageal cancer in 2002 had a 37.96% decline. The proportion of esophageal cancer among malignant tumors in different decades decreased significantly. CONCLUSION: The trend of the incidence rate of esophageal cancer had been decreasing for the last 29 years. The incidence rate in mountainous areas and hilly areas showed a declining trend while in the plain areas it remained steady but having slight increase in the recent years. The mortality rate of esophageal cancer had a significant decrease from 1969 to 2002.