Abstract
OBJECTIVE To investigate the clinicopathological features of esophageal carcinoma (EC) patients, and to analyze epidemiologic characteristics and the current situation of esophageal cancioma in the southern area of Hebei Province.
METHODS A total of 4329 patients with esophageal cancinoma, undergoing surgery in the Fourth Hospital of Hebei Medical University during a period from January 1996 to December 2005, were selected. Collection and statistical analysis of the pathologic data were performed using a SAS 6.0 software package.
RESULTS Over the past ten years, there has been a tendency for an increase in the mean age of EC onset (P < 0.05), a downtrend in the percentage of squamous cancer (SqCa) (P < 0.05) and an uptrend in the frequency of small cell carcinoma (P < 0.05). In clinical stages, there was a drop in the percentage of Stage-II squamous EC patients (P < 0.05), and an increase in that of Stage-IV patients (P < 0.05). There were statistical differences in sex, age, pathologic types, depth of infiltration, ratio of stages and lymph node metastasis, etc. among the superior, middle and inferior segments of the EC diseased region (P < 0.05).
CONCLUSION It was relatively late for the EC patients from this area to see a doctor, resulting in a drop in the ratio of SqCa and an ascensus in that of small cell cancer. However, due to a low incidence of adenocarcinoma, no obvious ascending tendency was found in the frequency of this carcinoma over the past ten years.
keywords
Introduction
In our study, clinical data from EC patients receiving surgical treatment in the 4th Hospital of Hebei Medical University, i.e. a cancer hospital in Shijiazhuang, the capital of Hebei province, was investigated by year-by-year observation, in order to determine the incidence of this disease in the southern area of Hebei Province, and to investigate oncogenesis and progression of EC.
Patients and Methods
Clinical data
All of the 4,329 patients were confirmed to have EC, and all patients selected had integrated surgical data from the Fourth Hospital of Hebei Medical University in Shijiazhuang, China, during a period from January 1, 1996 to December 31, 2005. EC histological typing was conducted based on the Practical Surgical Pathology, and the EC pathologic types were divided into squamous cancer (SqCa), adenocarcinoma, undifferentiated small cell carcinoma and Krukenberg tumors. Some rare carcinomas of pathologic types, such as the adenosquamous carcinoma, carcinosarcoma, glandular prickle cell carcinoma and undifferentiated carcinoma, etc., were included in other categories. The EC staging was performed in accordance with the 1997 UICC EC TNM staging standards. When a statistical analysis was conducted, Stage-IIa and IIb carcinomas were classified as Stage-II, and Stage-IVa and IVb tumors were classified as Stage-IV. See Table 1. for the clinical data of all the patients.
Clinical data from 4,329 patients with esophageal carcinoma.
Statistical analysis
A SAS6.0 statistical package was used, and the χ2, t-test and linear regression statistical methods employed. The value of α = 0.05 was adopted as a statistically significant difference, and α’ = α / [k (k - 1) / 2 + 1] as that of the partition of chi-square.
Results
General clinical features and change in trends
There were 2,879 male (66.5%) and 1,450 female patients (33.5%) in this study, with a male to female ratio of 1.99:1. There was no obvious change in the sex ratio over the past 10 years (P > 0.05, Table 1). Concerning the patients’ age of onset, the average value was 54.7 years in 1996, but increased to 59.1 in 2005. The 10-year mean age of onset was 57.1 years, showing an ascending tendency (P < 0.05).
Over the past 10 years, there were 582 patients with superior-segment EC (13.4%), 3,120 with middle-segment EC (72.0%) and 627 with inferior-segment EC (14.4%), with a stable incidence in the respective diseased regions (P > 0.05, Table 1).
Considering the pathologic types, there were 274 squamous-esophageal carcinoma patients in 1996 (94.8%), and 508 with the same disease in 2005 (91.9%). The percentage decreased to some extent (P < 0.05). There was only one case with small cell cancer in 1996 (0.3%), but the total number of cases with this cancer increased up to 16 in 2005 (4.6%), with a significant increase in the percentage (P < 0.05). There was no overt change with time compared to the incidence of other pathologic types (P > 0.05, Table 1).
As far as the infiltration depth was concerned, there were 97 cases with cancer in situ (2.4%). Infiltration of the submucosa, the superficial muscular and the deep muscular layers was respectively found in 371 (9.0%), 377 (9.2%) and 624 cases (15.2%). Invasion of the fibrous membrane layer and the peripheral soft tissue occurred in 2,302 (56.1%) and 336 cases (8.2%), respectively. Correlated information remained unavailable in 222 cases.
In 1996, Stage-II patients accounted for 66.3% of the totals (171 cases), and the ratio was 54.8% (294 cases) in 2005, with a significant drop in the percentage of Stage-II patients during the 10 years (P < 0.05). The frequency of Stage-IV patients was notably raised, with 0.4% in 1996 up to 2.8% in 2005 (P < 0.05).
During the 10 years, radical surgery was conducted for 4,092 patients (94.53%) and palliative surgery for 111 (2.6%). A total of 126 patients (2.9%) failed to receive a resection following an exploratory thoracotomy. Over the past 10 years, there was no overt change in the percentage of various modes of surgical operation (P > 0.05).
Relationship among the clinical correlated features
There was a significant difference in the male to female ratio between different diseased regions (P < 0.05). Male patients accounted for a majority of those with cancer at various sites, while female patients with inferior segment carcinoma accounted for the least proportion of the cancer patients (26%) (P’ > 0.0125, Table 2). There was a significant difference in the tumor sites of the patients at various ages (P < 0.05). The middle-aged and the advanced-age group cancer patients accounted for the highest proportion in the inferior-segment (40.7%). There was no obvious difference in the frequency at the superior segment and middle segment cancers between the two groups (P’ > 0.0125, Table 2).
The percentage of clinical correlation factors at various sites (%).
SqCa ranked first of all the tumors of all sites, adenocarcinoma accounted for 0.7% of the tumors in the superior and middle segments of the esophagus, and accounted for 7.9% of the tumors in the inferior seg-ment, which was significantly higher compared to the rate in the upper and middle part of the esophagus (P < 0.05, Table 3). Those with an encroachment in the fibrous membrane accounted for a majority of the deep-infiltrated cases, and there was a significant difference in the degree of infiltration depth among various sites (P < 0.05). With a descent in the sites, there was an increase in the proportion of the cases with an infiltration depth into the fibrous membrane (Table 2).
The percentages of pathologic types of cancers at various sites (%).
There was a significant difference in lymph node metastasis among different tumor sites (P < 0.05). Lymph node metastasis of EC cases was at a minimum when the tumor was located in the superior segment (22.98%), at a maximum in the inferior segment (45.56%) and the median in the middle segment of the esophagus (P’ < 0.0125, Table 2). The percentage of the metastasis accounted for 19.7%, 30.3% and 40.0% respectively at the superior, middle and inferior segments. In clinical stages, there was a significant difference among various sites (P < 0.05). Stage-II cancer accounted for a majority in all sites of the patients, and Stage-III and IV cancers were classified as middle-late stage diseases.
Discussion
EC is common in developing countries and areas, and usually the incidence is higher in males compared to females. The situation is basically the same in countries all over the world, with a similar male to female ratio in high-risk areas and a higher ratio in the low-risk areas. In China, the male to female ratio is approximately 2.0:1. Based on the data from our group, the male to female ratio was 1.99: 1, which is close to that recorded in previous literature.
Our study showed that EC was rare in young patients of less than 40 years old. There was an increase in the incidence of EC in people at or over 40 years, with a peak in the 50 to 59-year age group. Previous studies showed that patients at or over 50 years accounted for 80% of the total EC patients[1], similar to our findings. Based on data from our study, the mean age of onset of EC was 57.1 years. It was reported previously that the age of onset of EC occurred during middle and old-age, and with time there was an upward trend in the mean onset age[2,3]. Our findings were quite similar, which is probably related to an improvement in the local living standards, enhancement of health-care awareness and an increase in the proportion of people in an older age-group.
Based on overseas reports, there has been an uptrend in the incidence of esophageal adenocarcinoma over the last 20 to 30 years[4,5]. Adenocarcinoma accounted for only 1.7% of the cases in our study, and there was a significant upward tendency in the frequency over the past 10 years. So this trend might be related to a difference in the nature of the diet between the Chinese people and Westerners[6-11]. It would be of value to conduct further research on other special possible causes of oncogenesis and progression of esophageal adenocarcinoma in Shijiazhuang.
Our data showed that the percentage of Stage-II EC was significantly lowered over a 10-year period, while that of Stage-IV EC was greatly raised. This indicates that there was lack of adequate vigilance and general knowledge of the early EC symptoms by local residents of Shijiazhuang. This lack of education results in development of middle-late EC when a doctor is visited[12]. In some high-risk EC areas, the frequency of early visits has increased. The 5-year survival of EC patients has reached 40%[13], and the 5-year survival of early EC patients, after surgery, attained over 90%. It is thus evident that the keys for reducing the death rate, and for improving the patient’s quality of life are to reinforce secondary prevention, educate the general population regarding prevention of EC, increase mass screening, as well as improving early diagnosis and treatment. Postoperative combined therapy is essential for middle-late cancer patients who make up a majority of these cases.
Reports on the rate of EC excision have varied, with 90% and over in most reports[14]. In our hospital, the rate of EC excision has been raised from 60% over the past years to 90% and over. However, data from our study indicated there was no significant increase in the EC radical-cure or palliative excision rates which might be related to the decrease in Stage-II patients and an increase in Stage-IV cases, as well as more indication of surgery during the past ten years.
Our study showed that lymph node metastasis from EC was the highest with a tumor in the inferior segment of the esophagus (45.6%)[15], and was the lowest when the superior segment was involved. This finding allowed for a correlation between metastasis and the difference in lymph-vascular distribution and drainage, and a possible association with the difficulty during the operation in removing the lymph nodes at the superior segment around the carcinoma. Based on other literature, however, lymph node metastasis may occur more frequently from tumors in the middle segment of esophagus compared to other sites.
Regarding infiltration depth, the patients with an infiltration into the fibrous membrane at the inferior segment, and with advanced cancer as well, make up the majority of cases with the maximum lymphatic metastatic rate. This finding might be related to a high excision rate of cancers in the inferior segment and more indications for surgery.
The data in this report were provided by the medical staff of the Fourth Hospital (i.e. the Cancer Hospital), Hebei Medical University. However the information collected reflects only a portion of the patient’s conditions in the southern area of Hebei Province in China. More analyses and investigations are expected to validate the above data and the conclusions.
- Received August 19, 2007.
- Accepted December 3, 2007.
- Copyright © 2008 by Chinese Anti–Cancer Association
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