| Background: Human esophageal cancer (EC) is one of the most common malignant tumors, the mortality rate of esophageal cancer in China is the highest among the cancer mortality in the five continents, and esophageal cancer is the forth-leading causes of cancer death in China. Shexian in Hehei province located in the southern foot of Taihang Mountains, is one of the areas with the highest mortality rate in China. In recent years we have found that the incidence of cardia cancer in thid region were at a high level, there was a common phenomenon of high incidence of esophageal and gastric cardia. Studies have shown that nutritional deficiencies, poor eating habits of life, FHUGIC, as well as smoking and drinking were the facors of incidence of esophageal and cardiac risk. At present, esophageal carcinoma incidence rate and mortality is decreasing in high-risk areas of prevention and cure, however, the results were not expected. The majority of esophageal high-incidence areas which not match prevention and cure,the incidence and mortality still remain at a high level. Thougth the total incidence is descreasing, not all age groups is descended, thus the existence of enviroment or heredity carcinogenic agent cause prophylactic effect is disappointing. Primery prevention for eliminate or reduce carcinogenic factor is difficult to enforce because of cognitive level of disease in high-risk people and economic status. In circumstances of exact etiological factor and pathogenesy of esophageal cancer not yet conclusion, no matter in theory and in practice are quite a few problems on causal prophylaxis. Therefore, secondary prevention more and more attention for the past few years and endoscope screening was widespread performed in assistance of the Chinese cancer foundation. For research the correlation factors of the detection rate and the natural history of esophageal and cardic precursors, and find the suitable screeing interval to decrease interval cancer and raise the efficiency of screeing.Objective: First-round and repetitive endoscopic screening was performed among forty to sixty-nine year-old subjects in a high-risk region in shexian county, observe cardiaoesophagus detection rate of various lesions and its influencing factors and analyze the local esophgeal cancer and precursors morbidity situation and risk factors with the correlation data. To observe the natural history and find appropriate screening interval for esophageal and gastric cardia precursor. And analyze the relative risk of age, sex, family history of upper gastrointestinal cancer, smoking, drinking, presence of multiple esophageal Lugol-void lesions and dysplasia progression, then investigate the association between family history of upper gastrointestinal cancer and esophageal cardiac cancer in high-risk area population.Method: From March 2001 to December 2008, endoscopic screening was performed among villagers 40-69 years old of ten villages in Shexian County. The survey rate should be above 70%. After informed consent had been obtained, epidemiologist interviewed the individual to be examined to fill out a baseline questionnaire form, and the experienced endoscopists from the Fourth Hospital of Hebei Medical University performed the endoscopy with iodine staining to examine the esophagus, cardia, and the stomach till the duodenum was reached. The results were recorded in detail. Biopsy specimens were taken from all focal lesions and un-stained or lightly-stained places in the esophagus. If no focal lesions were observed, biopsies were taken at two standard sites, one at 25cm of esophagus and the other at the lesser curve near the posterior wall of the gastric cardia. The biopsy specimens were fixed in buffered formalin, embedded in paraffin, cut sections, and stained with hematoxylin, the diagnosis were made by pathologists. Invasive upper gastrointestinal carcinomas identified by the screening were referred to the Hebei provincial Tumor hospital for further treatment. Severe dysplasia, carcinoma in situ or intramucosal cancer cases were endoscopically treated by endoscopic mucosal resection or argon plasma coagulation(APC). After first-round endoscopic screening, repetitive endoscopic screenings were performed among forty to sixty-nine year-old subjects in a high-risk region in Northern China. Comparisons were made between the first and last screening result more than once. If the result suggests that a lesion has pathologically progressed, the time between the two screenings was recorded to deduce appropriate screening intervals. Case control study for analyse the relative risk of age, sex, family history of upper gastrointestinal cancer, smoking, drinking, presence of multiple esophageal Lugol-void lesions and dysplasia progression. The data were input the computer to set up a survey information database and handled by SPSS 13.0 software.Result: 1 First-screeing1.1 In total, 4,124 participants accepted the initial endoscopy screening, 51.8%(2135/4124) are males, 60.1%(2475/4124) were under 50-year-old, 34.3(1414/4124) reported a family history of upper gastrointestinal cancer (FHUGIC), 5.2%(213/4124)were multiple lugol-void lesions, 35.3% (1457/4124) were smoker or ex-smokers, and 15.2%(628/4124) were alcoholic drinkers.1.2 The detection rate of mild dysplasia (mD), moderate dysplasia (MD), severe dysplasia (SD), Cis/intramucosal carcinoma and invasive cancer was 15.4%(634/4124), 3.7%(153/4124), 1.5% (63/4124), 2.8% (117/4124) and 0.9% (37/4124) respectively.2 The effect factors of detection rate2.1 Position The detection rate of mD MD SD, Cis/intramucosal carcinoma and invasive cancer on the esophagus was 7.10%, 2.52%, 0.95%, 1.04% and 0.34% percent respectively, on the gastric cardia was 6.01%, 0.99%, 0.51%, 1.43% and 0.44% percent respectively, and on distant stomach was 2.26%, 0.19%, 0.07%, 0.36% and 0.12% respectively.2.2 Sex The detection rate of esophageal dysplasia on male and female was 11.9% (255/2135) and 9.1% (181/1989) respectively, the differece have statistical significance (χ~2=8.808,P=0.002). The detection of esophageal cancer was 1.97% (42/2135) and 0.75% (15/1989) respectively, the differece have statistical significance (χ~2=11.117,P=0.001).The detection rate of cardiac dysplasia on male and female was 9.2% (196/2135) and 5.7% (114/1989) respectively, the differece have statistical significance (χ~2=17.618,P<0.0005). The detection rate of cardiac cancer was 3.04% (65/2135) and 0.60% (12/1989) respectively, the differece have statistical significance (χ~2=33.497,P<0.0005). The detection rate of stomach dysplasia on male and female was 2.86% (61/2135) and 2.16% (43/1989) respectively, there are no significance difference (χ~2=2.025,P=0.093). The detection rate of stomach carcinoma was 0.80%(17/2135) and 0.15% (3/1989) respectively, the differece have statistical significance (χ~2=8.888,P=0.002).2.3 Age The detection rate of esophageal dysplasia of under 50 and above 50 was 6.00% (99/1649) and 13.6% (337/2475) respectively, the differece have statistical significance (χ~2=60.659 , P < 0.0005). The detection rate of esophageal cancer of under 50 and above 50 was 0.67% (11/1649) and 1.89% (46/2429) respectively, the differece have statistical significance (χ~2=10.308,P=0.001).The detection rate of cardiac dysplasia of under 50 and above 50 was 5.52% (91/1649) and 8.85% (219/2475) respectively, the differece have statistical significance (χ~2=15.785,P<0.0005). The detection rate of cardiac carcinoma of under 50 and above 50 was 0.61% (10/1649) and 2.71% (67/2475) respectively, the differece have statistical significance (χ~2=23.834,P<0.0005).The detection rate of stoamch dysplasia of under 50 and above 50 was 2.67% (44/1649) and 2.42%(60/2475) respectively, there are no significance difference (χ~2=0.240,P=0.347). The detection rate of stoamch carcinoma of under 50 and above 50 was 0.12% (2/1649) and 0.73% (18/2475) respectively, the differece have statistical significance (χ~2=7.526,P=0.004).2.4 Family history of cancer Familial cases show a significantly higher detection rate of mD, MD and SD in esophagus than the sporadic cases (P<0.05). There have difference in the detection of cis/intramucosal carcinoma and invasive cancer but have no statistical significance between familial and sporadic cases (P>0.05). There are no significant difference among the detection rate of different histologic types of cardiac mucosae between familial and sporadic cases (P>0.05). Familial cases of different histologic types of esophageal mucosae show a significantly younger age of onset than the sporadic cases (P<0.05), besides MD. In gastric cardiac, familial cases of only mD demonstrate a significantly younger age of onset than the sporadic cases (P<0.05).2.5 Multiple lugol-void lesions Among the 4124 screening candidates, multiple esophageal lugol-void lesions was found through esophagus iodine staining in 210 cases. The difference of detection rate of esophageal dysplasia on multiple esophageal lugol-void lesions positive cases and multiple esophageal lugol-void lesions negtive cases is significanct (P<0.0005), the difference of the detection rate of esophageal cancer have statistical significance (P<0.0005).3 Repetitive screening3.1 Of those initially screened subjects, 11.5% (475/4124) accepted repetive screenings. Comparison the results between the first and last screening and found 92 cases are dysplasia progression cases, there were 15 cases developed a secondary primary dysplastic lesion or carcinoma in situ at other locations of the esophagus after primary lesion had been resected by endoscopic mucosal resection.3.2 13 SD cases were found in repetitive screening: in two subjects 13 and 22 months after a baseline diagnosis of normal epithelium. In another subject 19 months after a baseline diagnosis of BCH. In four subjects 3, 4, 4, and 10.5 months after a baseline diagnosis of mD. In six subjects 6, 9, 12, 12.5, 17 and 44 months after a baseline diagnosis of MD.3.3 15 cis/intramucosal carcinoma cases in repetitive screening: in five subjects 12.5, 13, 24, 25 and 61 months after a baseline diagnosis of normal epithelium. In two subjects 16 and 48 months after a baseline diagnosis of mD. In four subjects 4, 6, 13 and 13 months after a baseline diagnosis of MD. In three subjects 3.5, 9 and 17.5 months after a baselin diagnosis of SD.3.4 4 invasive cancer cases in repetitive screening: in one subject 50 months after a baseline diagnosis of MD. In three subjects 14, 17 and 19 months after a baseline diagnosis of SD.4 The result of repetitive screening shows that the shortest interval time from baseline diagnosis of normal epithelium, BCH and mD progressed to carcinoma was 12.5 months and the shortest interval time from baseline diagnosis of MD and SD progressed to carcinoma is 3.5 months. So for avoid the development of interval cancer in interval time, a one-year frequency for the general population, the BCH and the mD subjects. A half-year frequency for the MD subjects are essential.5 The effect factors of dysplasia progression Those males, above 50 year-old, subjects with a positive family history of upper gastrointestinal, and with multiple lugol-void lesions showed a significantly risk of dysplastic progression, and the corresponding OR (95%CI) and P-value were 2.102 (1.325-3.336), 0.001, 2.001 (1.246-3.214), 0.004, 1.562 (1.010-2.416), 0.044, 3.062 (1.824-5.142), 0.000 respectively.Conclusion: 1 Male, above 50, a positive family history of upper gastrointestinal, with multiple lugol-void lesions and smoking does seem to increase the risk of esophageal cancer. Male, above 50 and smoking does seem to increase risk of cardiac carcinoma.2 The risk of dysplasia progression in male, above 50, a positive family history of upper gastrointestinal and with multiple lugol-void lesions is greater than female, under 50, a negative family history of upper gastrointestinal and with no multiple lugol-void lesions.3 For decrease the rate of missed diagnosis of early carcinoma, the interval time shoule be shorter for the natural history of rapidly developing precursors.4 The detection rate of esophageal dysplasia and carcinoma is increased because of family history of cancer, and the family history of cancer can effect the onset of age and number of primary lesions.
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