The Relationship between a Cohort Endoscopic Screening of 15,000 Subjects and the Death of Patients with Esophageal and Gastric Cancers in High-Risk Areas

Discussion

In areas at high risk for EC in China, this is the first time that endoscopic screening in a large population has been conducted. The results of 6-year follow-up have shown that there was a decrease of the death risk both in male and in female patients with EC, with a significant difference between the 2 groups. The decrease in death rates in the EC patients of the IVG closely related to the detection of early EC and precancerous changes via the endoscopic screening. A total of 97 cases in the IVG were diagnosed by iodine staining during endoscopic examination as esophageal squamous epithelium, carcinoma in situ at the cardiac glandular epithelium or intramucosal carcinoma, and 102 were found to have severe esophageal and cardiac atypical hyperplasia (Table 1).

Surgical procedures such as endoscopy-guided excision of the mucous membranes were performed in 90% of these patients. Treatment, which proved effective, interrupted the continuous progression of the lesion, and therefore, cut down on the mortality. It has been reported in China^[3] that in areas at high risk for EC, the postoperative 10-year survival rate of early EC patients diagnosed by endoscopic screening was 72.9%, and the 5-year survival rate of those undergoing endoscopy-guided mucosectomy was 100%. Katada et al.^[4] reported that the 5-year survival rate of patients who underwent an endoscopy-guided simple resection of lesions with infiltration of the muscularis mucosae was 79.5%. It was reported by Pech et al.^[5] that endoscopy-guided mucosectomy used for high-grade esophageal intraepithelial neoplasia and mucosal adenocarcinoma accompanied with Barrett’s esophagus was conducted in 349 patients, with a 5-year survival rate of 84%. Generally, it is believed that over time, the effect of endoscopic screening as increasing the long-term survival rate of ESC patients and decreasing the death rate may become more conspicuous.

However, the most significant concern in our study was that the RR of male GC patients in the IVG was 2.5, 9 CI (1.40-4.29), P = 0.01, compared to that in the CG, while for the female GC patients both at the age of 50 and of 65 years, the RR = 1.5-1.6. This was similar to the tendency of the RR of the male GC patients. Further, the total RR value of female GC patients was 0.99. Nevertheless, the differences were not statistically significant. Analysis of the results of cancer diagnosed via the endoscopic screening demonstrated that ESC and cardiac adenocarcinoma (CAC) detected early in male patients accounted for 84.5% and 25%, respectively, and those in females, accounted for 91.9% and 28.6%, respectively (Table 1). It suggested that the effect of the endoscopic examination on early detection of CAC was far lower than that on early detection of ESC. This phenomenon was also confirmed in our previous studies^[6]. Among the male patients who died of GC in the IVG, 60% were CGC patients (21/35), and in the females, it was 69.2% (9/13) (Tables 4, 5). It should be noted that the long-term survival rate of advanced CGC found by the endoscopic screening failed to increase, however, this could be attributed to the registration of tumor morbidity and the death rate occurring relatively earlier. Taken together, these 2 factors might underlie the finding that the RR of male GC patients was higher in the IVG than that in the CG; however, further in-depth analysis is necessary to differentiate between the females and males in this respect. In the male group, the RR of GC death cases was higher than in the controls while there was no such tendency in the female group.

In Japan, GC ranks first in the death rate for malignant tumors^[7]. In the world, Japan is the only country where an in-depth, large population-based GC screening and study were conducted. Hosokawa et al.^[8] conducted a retrospective cohort analysis of a population of 11,763 people, with an age ranging from 40 to 75 years. The results showed that in a comparison between the population with endoscopic screening and the control group, there was a decrease in the RR of the GC patients, RR = 0.35, 95% CI (0.14-0.86). In the study population, the RR of males was 0.22, (0.07-0.70). The author pointed out that early GC reached 78% via the endoscopic screening. After a cohort observation of 47,605 people, Miyamoto et al.^[9] found that there was a 46% decrease in the RR of GC patients who had undergone endoscopic examination, RR = 0.54, 95% CI (0.38-0.77). Currently there has been a 50% decrease in the death rate of both male and female Japanese GC patients. There is consensus that early diagnosis of GC decreased the death rate of the patients^[6]. In 2008, Hamashima et al.^[10] conducted an in-depth analysis of the role of the large population-based GC screening in reference to 4 aspects, i.e. X-rays, endoscopy, serum pepsin and HP antibody, based on 1,715 papers regarding the endoscopic screening of GC which were published in Japan during a period from 1985 to 2005. The authors then recommended that X-ray screening be the first choice for a large population if the opportunity to conduct population screening is available. Nevertheless, it was shown in an analysis of the relationship between the endoscopic screening and the early diagnosis of GC in Japan^[6,10,11] that in 2/3 of the Japanese GC patients, the pathogenic site was the gastric body or the pylorus. At present, local lesions have been found in 53% of GC cases diagnosed in Japan, while in the USA the rate is 27%. Of special concern is that if the intramucosal and sub-mucous lesions are regarded as the diagnostic criteria of early CGC, the early CGC would only account for 3.5% of the GC cases (204/5,863) in Japan, i.e., the level of early diagnosis of the distal GC would be higher than that of proximal GC in Japan. Likewise in China, it was seen in a study on endoscopic screening conducted in the EC high-risk area of Taihang Mountains^[12] that when intra-mucosal carcinoma was regarded as the defined standard of early ESC and CAC, the former accounted for 77.4% and the latter for 31.4% of the total cases. As it is well-known, based on the coding rules of the International Classification of Diseases, Eight Revision (ICD-8), CGC was classified according to the statistics of GC. In 2000, CGC was termed as adenocarcinoma of the esophagogastric junction by the WHO^[13]. Over the past 10 years, epidemiologic studies have shown that with a drop in the incidence and death rates of EC in the EC high-risk areas of China, there has been an apparent rise in the incidence of CGC^[14]. During a period from 1998 to 2002, the incidence rates of ESC and CGC in males respectively ranged from 82.5 to 123.5/100,000 and from 34.5 to 69.5/100,000 in the Ci-xian, Lin-xian and She-xian counties in Taihang Mountains, while in females, the incidence rates of ESC and CGC respectively ranged from 51.8 to 90.7/100,000 and from 10.3 to 41.4/100,000. The incidence rate of gastric adenocarcinoma could surpass that of ESC in the She-xian County in Hebei Province and in the Lin-xian County in Henan Province if commingling statistics of CGC and distal GC were conducted^[12]. It is obvious that attention should be directed to the incidence and death rates of CGC in the EC high-risk areas of China. Further, early diagnosis of CGC is the key to decreasing the death rates of upper gastrointestinal tumors in the EC high-risk areas.

Another significant finding from the follow-up data that we discovered is that in males, the death toll of EC in the age groups of 60-64 and 65-69 years accounted for 48% of the total cases (46/96), while in females of the same age groups, the proportion reached 42% (16/38) (Table 1). One specification in the project planning stipulated that the endoscopic screening rate should achieve 70%. However, since there was a long-held belief of an inherently poor prognosis of EC in the population in the high-risk areas, the screening rate failed to reach the design specification. It is believed that in the future, strengthening the understanding of early diagnosis and treatment of EC in the population of the advanced age group will raise the compliance of the public and awareness of the benefits of receiving endoscopic screening, and as a result, significantly cut down on the death rate of ESC in high-risk areas.