Endoscopic survey of esophageal cancer in a high-risk area of China

Abstract

AIM: To characterize the histological types of esophageal and cardiac mucosa by endoscopic survey of a population in a high-risk area of esophageal cancer of China.

METHODS: A selected cohort of residents in Cixian County during December 2001 and May 2002 was surveyed by using Lugol’s staining, followed by computer-based statistical analysis of the data with SPSS 10.0 software.

RESULTS: Histologically, the detection rates of squamous epithelial acanthosis, squamous epithelial atrophy, and basal cell hyperplasia in the esophagus were 1.9% (38/2013), 0.1% (3/2013) and 0.9% (18/2013) respectively, and those of mild, moderate, and severe esophagitis were 34.9% (703/2013), 1.6% (33/2013) and 0.2% (2/2013) respectively. Mild, moderate, and severe esophageal dysplasia were detected in 8.6% (172/2013), 7.8% (157/2013) and 2.6% (53/2013) respectively in the selected population, whereas in situ carcinoma, intramucosal carcinoma, invasive squamous carcinoma of the esophagus in 2.5% (50/2013), 0.2% (4/2013) and 0.7% (14/2013) respectively. The detection rates of non-atrophic gastritis and atrophic gastritis of the cardia were 36.3% (730/2013) and 11.5% (232/2013) respectively, with mild and severe dysplasia of the cardia detected in 2.5% (51/2013) and 0.8% (17/2013), respectively, in this population; the rates of intramucosal adenocarcinoma and invasive adenocarcinoma of the cardia were 0.1% (3/2013) and 0.8% (17/2013) respectively. The detection rate of esophageal cancer at early stage was 79.4% (54/68). The survey rate (ratio of examined population to expected population) was 73.8% (2013/2725).

CONCLUSION: Histologic types of the esophageal and cardiac mucosa were characterized by endoscopic survey in a high-risk population of esophageal cancer, which may help the early detection and treatment of esophageal and cardiac cancers and dysplasia, and reduce the mortality of such malignancies.

Key Words: $[Keywords]

INTRODUCTION

Esophageal cancer (EC) is one of the most common malignant tumors with a high incidence in such regions as China, Iran, South Africa, Uruguay, France and Italy[1], of which China has almost half of the total cases with also the highest mortality rate, the fourth leading cause of cancer-related deaths in China. According to the data derived from 1/10 sample death investigation in the whole population of China in 1990-1992, the mortality rate of esophageal cancer was 27.73/100000 for men and 13.63/100000 for women, which were 3.1 and 3.6 times, that reported by the World Health Organization (WHO) in 1998 respectively[2]. Some southern regions of the Taihang Mountains on the borders of Henan, Shanxi and Hebei provinces have significantly higher mortality rates of esophageal cancer. Cixian County in Hebei Province is also one of the areas with the highest mortality rate in China, where an endoscopic survey was conducted by Hebei Cancer Institute during the period between December 2001 and May 2002, and in this paper the results are reported.

MATERIALS AND METHODS

Cixian County is located at 36.30º northern latitude, 114.40º eastern longitude, on the east side of the Taihang Mountains along the Zhanghe River. It occupies an area about 1014 square kilometers with a population of 634470. This region contains greatly diverse geographic conditions, ranging from mountainous, hilly regions to long-stretched plains, each constituting about one-third of its total area. The climate is mainly under the influence of the warm seasonal wind from the mainland, with an annual average temperature of 18-25 °C and a rainfall between 600-700 mm. The dominant brown and light-colored soil yields mainly such farm products as wheat, corn, millet, rice, sweet potato and beans. Iron and coal are the main mineral resources, and the residents use coal mainly for daily cooking and heating[3].

As a key science research project sponsored by the National Tenth Five-Year Plan of China, the survey was conducted among the residents of 9 villages aged between 40 and 69 years in the hilly region of Cixian County, which is known for a higher incidence of esophageal cancer than the plain regions. The total population of the 9 villages was 12048, and the annual incidence and mortality rate of esophageal cancer in this region during 1996-2000 were 176.0/100000 and 126.2/100000 respectively.

Before the survey, a county-wide conference was convened by the local government participated by the local county, countryside and village leaders and cancer prevention professionals. At the conference, special committees were set up at each of the 3 administrative levels to be responsible for the execution of the survey in the areas where they perform daily duties. After the conference, the residents in the target areas were acknowledged of the benefits of such a massive survey through a propaganda campaign. On the basis of the government record of the residents, 2000 potential target subjects from the 9 villages were selected by the cancer prevention professionals, and two days prior to the survey, personal contacts with the subjects were made by local physicians to arrange for the details of the survey. At the beginning of the survey, the subjects were asked to fill an epidemiological questionnaire, followed by physical examination performed by the physicians to exclude persons with serious contraindications to endoscopy. Endoscopic examinations were then performed by specialists following the procedures described by Wang et al[4]. The detailed results were recorded and the biopsy specimens obtained were fixed in 80% alcohol and stained by hematoxylin-eosin (HE) for subsequent pathological diagnosis by pathologists.

Finally, the data were input into a computer to set up a survey information database and statistical analysis was performed using SPSS 10.0 software with chi-square test.

RESULTS

Survey rate

Of the totally 12048 residents of the 9 villages, 2992 were within the age range between 40 and 69 years, and after exclusion of 267 residents with contraindications (including 32 patients with cancer, 22 with heart diseases, 29 with cerebrovascular diseases, 55 with hypertension, 56 with other diseases, 59 already died, and 14 emigrants), the total number of subjects enrolled in this survey was 2013 (including 973 male and 1 040 female subjects, with the male to female ratio of 0.94:1), and the survey rate was therefore 73.8% (Table 1).

Table 1 Statistics of the residents of the 9 target villages enrolled in this survey.

Village	Total population	Aged between 40-69 (yr %)	Contrain- dication	Expected population	Examined population	Survey rate (%)
Hebei Village	1184	304 (25.7)	29	275	220	80.0
Taichen Village	1648	412 (25.0)	39	373	287	76.9
Xichengji Village	1682	381 (22.7)	53	328	283	86.3
Zhonghao Village	699	183 (26.2)	23	160	130	81.3
Donghao Village	1860	494 (26.6)	26	468	208	44.4
Chejiao Village	1618	383 (23.7)	38	345	276	80.0
Bai Village	1679	415 (24.7)	27	388	284	73.2
Donghelan Village	1076	271 (25.2)	17	254	208	81.9
Xihelan Village	602	149 (24.8)	15	134	117	87.3
Total	12048	2992 (24.8)	305	2725	2013	73.8

The percentages in bracket indicate the rates of the population aged 40-69 years.

Endoscopic findings of the esophagus

As shown in Table 2, the histologic detection rates of in situ carcinoma, intramucosal carcinoma, and invasive squamous carcinoma were 2.5% (50/2013), 0.2% (4/2013), and 0.7% (14/2013), respectively; early cancerous changes were detected in 2.7% (54/2013) of the subjects, which occupied 79.4% (54/68) of total esophageal cancer cases. Male subjects had comparable incidence of esophagitis [35.9% (349/973)] with that in female subjects [37.6% (391/1040), χ² = 0.645, P = 0.422], but had significantly higher incidence of dysplasia [23.1% (225/973) vs 15.1% (157/1040) in female, χ² = 21.072, P = 0.000]. The incidence of esophageal cancer did not vary significantly between the male and female subjects [3.3% (32/973) vs 3.5% (36/1040), χ² = 0.001, P = 0.98].

Table 2 Detection rates of the histologic changes in the esopha-gus (%).

Type	Male (%)	Female (%)	Total (%)
Normal squamous epithelium	308 (31.7)	392 (37.7)	700 (34.8)
Squamous epithelial acanthosis	19 (2.0)	19 (1.8)	38 (1.9)
Squamous epithelial atrophy	1 (0.1)	2 (0.2)	3 (0.1)
Esophagitis
Mild	337 (34.6)	366 (35.2)	703 (34.9)
Moderate	11 (1.1)	22 (2.1)	33 (1.6)
Severe	1 (0.1)	3 (0.3)	4 (0.2)
Dysplasia
Mild	114 (11.7)	58 (5.6)	172 (8.6)
Moderate	82 (8.4)	75 (7.2)	157 (7.8)
Severe	29 (3.0)	24 (2.3)	53 (2.6)
In situ carcinoma	25 (2.6)	25 (2.4)	50 (2.5)
Intramucosal carcinoma	2 (0.2)	2 (0.2)	4 (0.2)
Invasive carcinoma	5 (0.5)	9 (0.9)	14 (0.7)
Others	31 (3.2)	33 (3.2)	64 (3.2)
Total	973 (100.0)	1040 (100.0)	2013 (100.0)

Table 3 shows that with a 5-year increase in age, the histologic incidence of esophageal cancer and dysplasia all tended to be increased from the relatively low level in the 40-year-old group to the highest in the 65-year-old group (trend ^aχ² = 135.943, ^aP = 0.000; trend ^bχ² = 182.782, ^bP = 0.000). The rates of esophagitis in different age groups varied significantly (χ² = 12.475, P = 0.029), as well as the rates of dysplasia (χ² = 141.184, P = 0.000), and esophageal cancer (χ² = 74.855, P = 0.000).

Table 3 Age-related distribution of the incidence of pathological changes in esophagus.

Type	Age [yr (%)]
	40-	45-	50-	55-	60-	65-69
Normal squamous epithelium	355 (44.8)	176 (38.4)	92 (28.6)	56 (24.9)	14 (9.4)	7 (10.4)
Squamous epithelial acanthosis	11 (1.4)	4 (0.9)	10 (3.1)	7 (3.1)	5 (3.4)	1 (1.5)
Squamous epithelial atrophy	1 (0.1)	1 (0.2)	1 (0.3)	-	-	-
Basal cell hyperplasia	6 (0.8)	6 (1.3)	3 (0.9)	1 (0.4)	2 (1.3)	-
Esophagitis
Mild	304 (38.4)	167 (36.5)	90 (28.0)	71 (31.6)	53 (35.6)	18 (26.9)
Moderate	17 (2.1)	2 (0.4)	9 (2.8)	4 (1.8)	1 (0.7)	-
Severe		1 (0.2)	2 (0.6)	1 (0.4)	-	-
Dysplasia
Mild	37 (4.7)	36 (7.9)	41 (12.7)	26 (11.6)	21 (14.1)	11 (16.4)
Moderate	19 (2.4)	30 (6.6)	43 (13.4)	26 (11.6)	26 (17.4)	13 (19.4)
Severe	12 (1.5)	12 (2.6)	12 (3.7)	6 (2.7)	9 (6.0)	2 (3.0)
In situ carcinoma	3 (0.4)	8 (1.7)	10 (3.1)	14 (6.2)	8 (5.4)	7 (10.4)
Intramucosal carcinoma	-	2 (0.4)	-	-	2 (1.3)	-
Invasive carcinoma	-	2 (0.4)	3 (0.9)	4 (1.8)	3 (2.0)	2 (3.0)
Others	27 (3.4)	11 (2.4)	6 (1.8)	9 (4.0)	5 (3.4)	6 (9.0)
Total	792 (100.0)	458 (100.0)	322 (100.0)	225 (100.0)	149 (100.0)	67 (100.0)

Endoscopic findings of the gastric cardia

The incidence of cardiac cancer was much lower than that of esophageal cancer (χ² = 26.767, P = 0.000), and early cardiac cancer only occupied 15% (3/20) of cardiac cancer cases. The rates of gastritis involving the cardia were 44.5% (433/973) in male and 50.8% (529/1 040) in female subjects, showing significant difference between them (χ² = 8.159, P = 0.004). The rates of dysplasia also varied significantly between them [4.9% (48/973) in male vs 1.9% (20/1 040) in female, χ² = 13.955, P = 0.000], but not that of cardiac cancer, [1.3%(13/973) in male vs 0.7% (7/1040) in female, χ² = 2.246, P = 0.134], as shown in Table 4.

Table 4 Incidence of pathological changes detected histologi-cally in the cardia (%).

Type	Male (%)	Female (%)	Total (%)
Normal adenoepithelium	301 (31.0)	329 (31.7)	630 (31.4)
Non-atrophic gastritis	323 (33.2)	407 (39.1)	730 (36.3)
Atrophic gastritis	110 (11.3)	122 (11.7)	232 (11.5)
Dysplasia
Mild	36 (3.7)	15 (1.4)	51 (2.5)
Severe	12 (1.2)	5 (0.5)	17 (0.8)
Intramucosal adenocarcinoma	1 (0.1)	2 (0.2)	3 (0.1)
Invasive adenocarcinoma	12 (1.2)	5 (0.5)	17 (0.8)
Others	178 (18.3)	155 (14.9)	333 (16.5)
Total	973 (100.0)	1040 (100.0)	2013 (100.0)

At a 5-year interval, the incidence of cardiac cancer and dysplasia both increased from the level in the 40-year-old group to the highest in the 65-year-old group (trend ^aχ² = 84.875, ^aP = 0.000; trend ^bχ² = 36.209, ^bP = 0.000, Table 5). The rates of gastritis involving the cardia and dysplasia of the cardia also varied significantly (χ² = 11.223, P = 0.047; χ² = 18.901, P = 0.002), as well as that of cardiac cancer (χ² = 43.351, P = 0.000).

Table 5 Age-related distribution of detection rates of pathological changes in gastric cardia.

Type	Age [yr (%)]
	40-	45-	50-	55-	60-	65-
Normal adenoepithelium	295 (37.2)	156 (34.1)	81 (25.2)	61 (27.1)	27 (18.1)	10 (14.9)
Non-atrophic gastritis	319 (40.3)	169 (36.9)	116 (36.0)	60 (26.7)	47 (31.5)	19 (28.4)
Atrophic gastritis	90 (11.4)	45 (9.8)	38 (11.8)	34 (15.1)	14 (9.4)	11 (16.4)
Dysplasia
Mild	13 (1.6)	8 (1.7)	10 (3.1)	8 (3.6)	8 (5.4)	4 (6.0)
Severe	-	8 (1.7)	2 (0.6)	3 (1.3)	4 (2.7)	-
Intramucosal adenocarcinoma	-	-	1 (0.3)	-	1 (0.7)	1 (1.5)
Invasive adenocarcinoma	-	1(0.2)	1 (0.3)	3 (1.3)	5 (3.4)	7 (10.4)
Others	75 (9.5)	71 (15.5)	73 (22.6)	56 (24.9)	43 (28.9)	15 (22.4)
Total	792 (100.0)	458 (100.0)	322 (100.0)	225 (100.0)	149 (100.0)	67 (100.0)

DISCUSSION

The prognosis of esophageal and cardiac cancer is the poorest among the patients with digestive carcinomas as more than 90% of them are not clinically identified until at an advanced stage, when surgery is defied due to either local tumor invading the surrounding tissues or distant metastasis, and therefore the 5-year survival rate of esophageal cancer is below 10%[5-7]. Early-stage asymptomatic esophageal cancer is basically curable with, for instance, conventional surgery and endoscopic resection, resulting in a 5-year survival rate of the patients reaching 90% or above[8-10].

For esophageal cancer prevention and treatment, a series of systematic researches including clinical, laboratory and field investigation were carried out in high-risk areas such as Linxian and Cixian counties since 1959[11-16], but at present the etiological factors have not yet been identified, and the incidence and mortality rates of esophageal cancer still remain high in those areas. A variety of detecting methods have been attempted by Chinese scientists to identify early esophageal cancer and precancerous lesions, such as exfoliative balloon cytology (EBC), occult blood bead (OBB), conventional endoscopy with smear or biopsy, sparse hydrochloric acid preliminary screening, serum total salic acid detection (TSA), otolaryngologic examination and so forth, but all these methods are marred by certain disadvantages besides their respective advantages in the early detection of esophageal cancer and precancerous lesions[17-19].

A massive screening in the population of 126187 in Cixian was carried out by Hebei Cancer Institute and 16748 high risk participants aged 40 years and older were screened with exfoliative balloon cytology, the survey rate was 71.4%, resulting in the identification of 179 cases of esophageal cancer, 172 esophageal precancerous lesions, 866 stage II severe esophageal epithelial dysplasia (SEED II), 3179 stage I severe esophageal epithelial dysplasia (SEED I) and 5 346 mild esophageal epithelium dysplasia (MEED), with the detection rates of MEED, SEED I, SEED II, esophageal precancerous lesions and esophageal cancer being 31.92%, 18.98%, 5.17%, 1.03% and 1.07%, respectively[20]. Most of the researches indicate that exfoliative balloon cytology is an effective, economic and practicable method, having higher detection rate for esophageal cancer than conventional endoscopy, but only cytological diagnosis is obtained and a further endoscopic biopsy and histopathologic confirmation are necessary. This method is now insufficient for esophageal cancer screening because of the severe discomfort and low acceptance by the target subjects.

Esophageal chromoendoscopy with multi-point biopsy and histopathologic examination has developed rapidly since 1974, which greatly increased the detection rate of esophageal cancer and precancerous lesions, and at the same time it is capable of characterizing and defining the scope of the lesions to provide guidance for treatment and follow-up, also suitable for the secondary prevention of esophageal cancer[4,21-33]. Currently the secondary prevention with early detection, early diagnosis and early treatment through chromoendoscopy survey has become the major research concern in the prevention and control of esophageal cancer.

The occurrence and development of esophageal cancer is a slow process involving multiple factors and genes and undergoing multiple stages. Prior to cancerization of the squamous esophageal epithelium, the basal cell hyperplasia or simple hyperplasia takes place and evolves into mild, moderate, severe dysplasia cells that develop, in sequence, into in situ carcinoma, early invasive cancer and advanced cancer[34-36]. As a part of the entire research project, a massive esophageal chromoendoscopic survey was initially conducted in the high-risk area without preliminary screening, and the high survey rate reaching 73.8% indicates that the population’s compliance to the survey was high after adequate health education. The distribution of histologic types of the esophageal and cardiac mucosa in high-risk area can be accurately obtained by esophageal chromoendoscopic survey, which possesses the advantage of accurate pathologic diagnosis and differentiation of the histologic types, well defined scope of the lesions and their invasive depth.

This study will, after defining the incidences of the pathological changes of the esophageal and cardiac mucosa in the population, contribute to the early treatment of esophageal and cardiac cancer and dysplasia, increase their cure rates, and reduce the mortality of such malignancies.