| 1 Background and objective of researchGastric cardia adenocarcinoma is one of the most common upper gastrointestinal malignant tumors in the northern part of Henan province, which has a very high incidence of GCA, with more than 190 cases per 100000 populations annual. The early symptoms of GCA are hidden and atypical which lead to a result that when diagnosed, the majority of the patients have been in the advanced stage, with poor prognosis and the postoperative survival rate is less than 30%.For nearly half a century, the morbidity of gastric cardia adenocarcinoma has presented a rising tendency significantly around the world. Gastric cardia adenocarcinoma is threatening human life seriously. Because of the significant difference between Chinese and Western scientists about the understanding of GC, so far there is no unified standard of cardia cancer staging. Nowadays gastric cardia adenocarcinoma has become a heat point that researched by scientists from all over the world competitively and reports concerning the pathogenesis and biological behavior have been emerging endlessly, however the studies with large sample involving the clinic pathological feature of varying invasion depth and the effect on survival period are rare, and there is no final conclusion about the status of lymph node metastasis. In regard of other kinds of cancers, it has been confirmed that invasion depth is highly related to lymph node metastasis. The invasion depth is an important incidence index when confirming the treatment and TNM. In recent years, the rapid development of endoscopy technology, especially the clinical popularity of Endoscopic ultrasonography, has made invasion depth a clinical pathological indicator which could be obtained in a noninvasive way. And the application of endoscopic mucosal resection and endoscopic mucosal dissection has made it possible to completely heal gastric cardia adenocarcinoma, the invasion depth of which is within the submucous layer. This shows that the invasion depth of gastric cardia adenocarcinoma is of great significance to clinical practice, especially for the endoscopic mucosal minimally invasive therapy at early stage, and the confirmation of invasion depth is the key to the success of the treatment. Therefore, this research, the research objects of which are the 34868 selected patients with gastric cardia adenocarcinoma whose invasion depth has been recorded clearly and the main line of which is about the depth of invasion, analyzes the interaction between the different invasion depth and gender, age, year of making diagnosis, high/low incidence area, family history of cancer, gross type of the cancer, tumor location, longest diameter of the cancer, differentiation degree, lymph node metastasis and distant organ metastasis and discusses the possibility of predicting the positive events such as lymph node metastasis, distant organ metastasis and so on according to invasion depth and the influences that invasion depth has on the lifetime, so that we can provide a reliable basis for clinical diagnosis and treatment of gastric cardia adenocarcinoma.2 Materials and Methods 2.1 Research objectsAll the sample data and information used in this research are from Henan Key Laboratory for Esophageal Cancer Research. The standard of selecting patients with gastric cardia adenocarcinoma are that patients diagnosed with gastric cardia adenocarcinoma between 1973 to 2013 and their invasion degree, as known as T stage, is recorded clearly. The number of patients that meet the selection criteria is in total 34868. 27169 cases are male with an average age of 60.66±8.82, median age of 61. The average of the 7699 female patients is 60.00±8.90, and the median age of them is 60. Male and female ratio is 3.52: 1. 2.2 Patient Information of GCA and Sample CollectionSince 2009, our research group has started the information collecting work in large-scale for cases of GCA. The usual approaches we adopted to collect information of patients are as follow: 1.We conducted our work based on the unit of family from high incidence area of GCA, and we adopted questionnaires in patients’ homes to collect and record their basic information and living conditions, according to the patients information, we went to the hospital which the patients were treated in to re-check, verify and supplement the clinical information.2. We established cooperative relationship with local hospital from high incidence area of GCA and set up research center, which enabled us to collect information clinical case for GCA at regular intervals.3.We collected basic information of GCA patients from Centers for Disease Control in different regions, after that we went to hospital of treatment to supplement related pathological information. 2.3 Living Status Follow-upIn this research, we have 20331 out of the total of 34868 cases of GCA with complete information including family addresses and contact ways. Firstly, we adopted follow-up phone calls, and secondly we choose household surveys to implement the detailed living conditions of the patients, and detailed record of death dates and death reasons for the dead. The patients’ death regarded as the termination events of the follow-up. The follow-up of this group for GCA patients began at April 1984, and 12294 cases were followed up successfully by Oct. 2014 with 35.3% success rate of follow-up. 2.4 Statistical MethodSPSS 21.0 was used for statistical analysis of data. The involved statistical methods included: x2 test, one-way ANOVA, Spearman rank correlation, Logistic regression, Kaplan-Meier survival estimate, Proportional Hazard Model –Cox’s Regression, and ROC curve. The test standard: α=0.05. 3 Results 3.1 Clinical Distribution Characteristics of GCA PatientsIn this research, we selected a total of 34,868 GCA patients and the diagnose time span exceeded 40 years. The number of patients in high incidence area was absolutely dominant, 2.69 times of that in low incidence area. The proportion of patients with a family history of positive cancer was nearly 30%. There were 27,169 male patients and 7,699 female patients, and the male female ratio was 3.52: 1. With the increasing age of diagnosis, the male female ratio gradually increased. The number of GCA patients was the largest at the age of 60 to 70 in both male and female groups. The proportion of male patients at the age ≥70 was the highest(79.9%), while the proportion of female patients at the age <50 was the highest(24.2%). The average age of onset of GCA and median age were about 60, but the average age of onset of male patients and median age were slightly higher than those of female patients. The material showed that GCA was mostly located in cardiac part; the gross type of early cancer was pitting, while the gross type of middle and late cancers was locally ulcerative. Most of tumors had the longest diameter of 3-6cm, accounting for over half, while the number of tumors at the longest diameter below 3cm was smallest. The differentiated degree of GCA was mainly the lowest, accounting for 50.3%, while the second lowest was moderate differentiation, accounting for 43.6%. Most cancers had the invasion depths in T3+T4. In this material, the number of patients with positive lymph node metastasis was 1.83 times of negative ones, while the number of patients suffering distant organ metastasis only accounted for 0.8% of the total number. 3.2 Relationship between GCA Invasion Depth and Clinical and Pathological CharacteristicsThe stages of Tis+T1, there were a total of 1,224 patients, accounting for 3.5%. In the stage of T2, there were 8,358 patients, accounting for 24%. In the stage of T3+T4, there were 25,286 patients, accounting for 72.5%. When GCA patients were reminded to receive treatment, most of them were in the middle and late stage. In the stage of Tis+T1, the number of patients at the age <50 years was the largest; In the stage of T3+T4, the number of patients at the age ≥70 was the largest. With the increasing year of diagnosis, the proportion of patients in T2 stage showed a declining trend. The distribution of invasion depths in various stages was different. In the stage of Tis+T1, the distribution showed an increasing trend, indicating the increase of early diagnosis rate in recent years. The distribution of GCA invasion depths had no difference between the two genders. In the stage of Tis+T1, the proportion in high incidence area of esophageal cancer was higher than that in low incidence area. In the stages of T2 and T3+T4, the distribution was mainly in low incidence area. The number of patients in high incidence area was 2.7 times of that in low incidence area. Different from patients with a family history of negative cancer, the distribution was mainly in the stages of Tis+T1 and T2 among patients with positive cancer. The invasion depth was significantly correlated to the longest diameter of tumor, namely, with the increase of the longest diameter of tumor, the invasion depth gradually increased. The differentiated degree was correlated to invasion depth, namely, the poorer the differentiated was, the longer the overall invasion depth of tumor was. The distribution of gross types was different in different invasion depths: the gross type was mainly plain in the stage of Tis, protruded in the stage of T1 and mostly locally ulcerative in the middle and late stages. With the increase of invasion depth, the lymph node tended to positive metastasis. This material showed that when the invasion depth was in the stage of Tis+T1, the positive lymph node metastasis rate was 16.5%; in the stage of T2, the rate was 54.8%; in the stage of T3, the rate was 70.2%. The number of patients with positive lymph node metastasis was 1.8 times of patients with negative lymph node metastasis. For distant organ metastasis, the patients in T3+T4 were significantly more than patients in Tis + T1 and T2. 3.3 Impacts of Different Invasion Depths and Clinical and Pathological Characteristics on Survival PeriodsThe survival periods were greatly different in different invasion depths. The median survival time in Tis+T1 was the longest, namely 16.088 years, 4.43 times of that in T3+T4, and the second longest survival time was in T2, namely 4.422 years. The median survival time declined significantly with the increase of invasion depth. The single-factor survival analysis showed that the age of diagnosis, family history of tumor, gross type, differentiated degree, invasion depth, lymph node metastasis, and distant organ metastasis and the longest diameter of tumor were the influencing factors of prognosis of GCA patients. The multi-factor survival analysis showed that the impact of lymph node metastasis on survival period was the most significant, followed by invasion depth and differentiated degree. 4 Conclusions1) As one of the important biological behaviors of GCA, invasion depth is closely related to clinical and pathological characteristics. The lymph node metastasis, differentiated degree and the longest diameter of tumor are most closely related to invasion depth. The invasion depth is positively correlated to the longest diameter of tumor and lymph node metastasis. With the worsening of differentiated degree, the overall invasion depth shows an increase trend. When the invasion depth exceeds submucosa, the lymph node metastasis rate greatly increases. The lymph node metastasis rate is up to 70% when the invasion depth exceeds serosa layer.2) Gender is one of the risk factors of GCA. The risk of male GCA is greater than that of female GCA and the male and female illness ratio can reach 3.52:1. The proportion of women in GCA patients deceases with the increase of age. The estrogen may be one risk factor of GCA.3) In recent 10 years, the proportion of GCA patients in T3+T4 has increased; the survival time significantly declined relative to that of 10 years ago. The grade malignancy of GCA may increase.4) The invasion depth of GCA is significantly correlated to gross type. In the gross type of early cancer, the cancer in situ was mainly flat-type and in T1, the cancer is mainly pitting-type. In the gross type of middle and late cancers, the majority of cancers are invasion uncreative-type in T2; in T3 and T4, the cancers are mainly local uncreative-type.5) The age of diagnosis, family history of tumor, gross type, differentiated degree, invasion depth, lymph node metastasis, distant organ metastasis and the longest diameter of tumor are the influencing factors of prognosis of GCA patients. The impact of lymph node metastasis is the most significant. |
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