|Year : 2016 | Volume
| Issue : 4 | Page : 499-504
Clinical observation and retrospective study of the influential factors of liver metastasis in 306 cases of colon cancer
X Lin1, M Lin2, X Wei3, Q Chen4
1 Department of Oncology, Fujian Provincial Hospital, Fuzhou, Fujian, PR China
2 Department of Oncology, Fujian Medical University Union Hospital, Fuzhou, Fujian, PR China
3 Department of Pharmacy, Fujian Provincial Hospital, Fuzhou, Fujian, PR China
4 Department of Oncology, Fujian Medical University Union Hospital; Fujian Key Laboratory of Translational Cancer Medicine; Fujian Medical University Stem Cell Research Institute, Fuzhou, Fujian, PR China
|Date of Web Publication||21-Apr-2017|
Department of Oncology, Fujian Medical University Union Hospital; Fujian Key Laboratory of Translational Cancer Medicine; Fujian Medical University Stem Cell Research Institute, Fuzhou, Fujian
Source of Support: None, Conflict of Interest: None
PURPOSES/OBJECTIVES: By observing and analyzing the clinical features of the colon cancer and the influence factors of liver metastasis, we try to find out independent risk factors with significant influence on colon cancer liver metastasis as well as to provide reference for clinical treatment. MATERIALS AND METHODS: A total of 306 cases of colon cancer patients' clinical data, including gender, age, primary focal size, primary focal intestinal segment, degree of differentiation, infiltration depth, level of serum carcinoembryonic antigen (CEA) before surgery, lymph node metastasis, liver basic diseases were collected and recorded. Single-factor Chi-square analysis and multifactor logistic regression analysis (SPSS 16.0 software) were used to retrospectively study the possible influence factors of colon liver metastases and to preliminary discuss the potential risk factors of liver metastasis in colon cancer patients. RESULTS: The Chi-square analysis showed that patients' primary focal segment, degree of differentiation, infiltration depth, level of serum CEA before surgery, and states of hepatitis B does 2 half-and-half had significant effect on the incidence of liver metastasis. However, in the further logistic regression analysis, it showed that only the infiltration depth and the states of hepatitis B does 2 half-and-half were the independent risk factors that influence the hepatic metastases. What was more, the both subgroups of positive hepatitis B with infection and vaccine showed significant statistical differences when comparing with hepatitis B all negative in the event of the probability of liver metastases (P = 0.011 and 0.004). CONCLUSIONS: The infiltration depth and the states of hepatitis B does 2 half-and-half were the independent risk factors on colon cancer patients' hepatic metastases. Those with the infiltration depth of T4 had a higher rate of hepatic metastases. Patients with does 2 half-and-half-positive hepatitis B (whether subgroup of hepatitis B virus infection or subgroup hepatitis B vaccine related) had a lower incidence rate of liver metastasis than those with hepatitis B all negative.
Keywords: Colon cancer, hepatitis B, liver metastasis
|How to cite this article:|
Lin X, Lin M, Wei X, Chen Q. Clinical observation and retrospective study of the influential factors of liver metastasis in 306 cases of colon cancer. Indian J Cancer 2016;53:499-504
|How to cite this URL:|
Lin X, Lin M, Wei X, Chen Q. Clinical observation and retrospective study of the influential factors of liver metastasis in 306 cases of colon cancer. Indian J Cancer [serial online] 2016 [cited 2020 Aug 5];53:499-504. Available from: http://www.indianjcancer.com/text.asp?2016/53/4/499/204782
| » Introduction|| |
Colon cancer is one of the most common alimentary canal malignancies, the primary cause that led colon cancer patients to death is distant metastasis, and liver is the most common seen target organ of distant metastasis. According to relative reports, there were about 10%–25% colorectal cancer patients with liver metastasis when they were made a definite diagnosis, and about 25% patients come up with heterochrony hepatic metastases.,, Liver itself has the specificity of dual blood supply, which avails the implantation and the proliferation in liver of cancer embolus and formation of metastasis focus. Nowadays, with the rapid development of social economy and appearance of new technology and new materials in China, although clinical efficacy has been largely improved with the help of multidisciplinary comprehensive treatment, the rate of colon cancer patients who die of distant metastasis still stay high. Hence, it is essential for colon cancer patients to foresee and prevent distant metastasis. However, what were the independent risk factors of liver metastasis was still unsure clinically right now. This research analyzed retrospectively the clinical material of 306 cases of colon cancer patients in our hospital's medical oncology since March 2011–December 2015, to discuss the correlation of potential risk factors such as liver underlying diseases and colon cancer with liver metastasis, with the purpose of offering reference to this kind of patients during the clinical treatment.
Besides, hepatitis B does 2 half-and-half is the thing that most common serum marker which can be detected for infection by hepatitis B virus (HBV). HBV infection is very populated in China. HBV immunology shows that there are three groups of marks, which are hepatitis B surface antigen, hepatitis B surface antibody, hepatitis B e antigen, hepatitis B e antibody (HbeAb), and hepatitis B core antibody. The significant of detection is to see whether be caught by HBV or not. This study especially observed the correlation of states of hepatitis B does 2 half-and-half and liver metastasis in colon cancer patients.
| » Materials and Methods|| |
Objective of study
This clinical research included colon cancer patients who were adopted by medical oncology, Fujian Province Hospital, from March 2011 to December 2015 and were made a definite primary focus diagnosis by histopathology examination. Excluding patients that existence of carcinoma of anal canal, not-doing-treatment of primary focus, uncertainty of primary focus, combination of other places' malignancies, number of inspection area of surgery's lymph that <12, pregnant women, occurrence of colon cancer within 1 year after giving birth, and cases without liver computed tomography (CT)/magnetic resonance (MR) strengthened image-scanning.
The record included patients' gender, age, type of primary focus, part of primary cancer in intestinal segment, size of primary focus, depth of infiltration (T-stage), differentiated degree, level of serum carcinoembryonic antigen (CEA) before surgery, metastasis of lymphonodus and its number, first time that discovered and diagnose colon cancer, liver metastasis, meanwhile whether liver with or without any other diseases (fatty liver, liver cirrhosis, HBV hepatitis).
Diagnostic criteria and staging criteria
Three hundred and six patients in this research were all proved to have adenocarcinoma, according to the fourth edition diagnostic criteria of digestive system tumor World Health Organization (WHO) classification of pathology. We take surgery inspect record as standard to judge whether lymph node metastasis and its transfer number All cases of hepatic metastasis must take CT/MR scan by at least one technologist-in-charge and draw out the conclusions. Tumor, node, metastasis period was followed by the standard of colon cancer NCCN guide (2015, version 1). What was more, the rate of metastasis of lymphonodus mentioned in this research equaled to the cases' number of metastasis of lymphonodus/total subgroup cases' number × 100%; the degree of metastasis of lymphonodus = the number of metastasis of lymphonodus/total check number in subgroup × 100%.
Gender, age, intestinal segment of the primary focus, size of the primary focus, depth of infiltration, differentiated degree, level of serum CEA before surgery, situation of metastasis of lymphonodus, and clinical data such as liver underlying diseases of 306 cases of colon cancer patients were observed and recorded. SPSS 16.0 (Chicago, U.S.) statistical software was used for the analysis of collected data. For single-factor analysis, Chi-square test was used, while for multifactor analysis, binomial logistic regression analysis was used. Calculating each factor's dominance ratio to liver metastasis (odds ratio value), estimating the relative risk, and 95% confidence interval, seeing that whether there were statistical differences between subgroups or not, P< 0.05 was seen having statistical significance.
| » Results|| |
Observation and comparison of colon cancer patients' ordinary data
In the collection of 306 cases of colon cancer patients, according to the standard of colon cancer NCCN guide (2015, version 1), the number of first diagnosis that unreached IV period was 245 cases (including 37 cases in early period of I–IIa, 208 cases in later period of IIb–IIIc), as well as 61 cases of distant metastasis, period IV. [Table 1] shows patients' ordinary data such as gender, age, part of primary focus in intestinal segment, size of cancer, depth of infiltration (T-stage), differentiated degree into representation, and statistics. Using the SPSS 16.0 to do the single-factor, Chi-square test was used; this study observed and analyzed the influence on the rate of colon liver metastases. There were no statistical differences in gender, age, size of primary focus in liver metastases; however, the cancer's depth of infiltration, part of primary focus in intestinal segment, differentiated degree, and level of serum CEA before surgery had significant correlation with the rate of colon liver metastases in single-factor analysis (as there were only four cases of mucinous adenocarcinoma in this type, and all of whom without liver metastases, it was too less to be discussed on the correlation between two of them, which needed a further study).
|Table 1: Observation of colon cancer patients' correlation analysis of liver metastases|
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Observation and comparison of the situation of patients' lymphatic metastasis
There were 99 cases of regional metastasis of lymphonodus in 306 cases of colon cancer patients, in which 13 cases had hepatic metastases at the same time, and it took 13.1% of the patients in this subgroup. Nonregional-metastasis-of-lymphonodus was observed in 119 cases, in which 12 cases had hepatic metastases. SPSS 16.0 software was used to analyze patients' situation of lymphatic metastasis in comparison. Single-factor Chi-square test was used to analyze the influence on the colon liver metastases. The result showed that χ2 = 2.383, P = 0.123, without statistical differences. The result is shown in [Table 2].
|Table 2: Influence of the situation of colon cancer patients intervallo rectal adenocarcinoma lymphonodus on hepatic metastases|
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The situation of colon cancer patients' liver original disease
Situation of colon cancer patients' hepatic metastases with fatty liver
Of 306 cases of colon cancer patients, 17 cases had fatty liver examined by CT/MR, and 1 case of them had hepatic metastases. The result of influence of fatty liver on colon liver metastases is shown in [Table 3], χ2 = 0.006, P = 0.937, without statistical differences. The result is shown in [Table 3].
|Table 3: Influence of with or without fatty liver on hepatic metastases in colon cancer patients|
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Situation of colon cancer patients' hepatic metastases with liver cirrhosis
Of 306 cases of colon cancer patients, 4 cases had liver cirrhosis, which was shown by image examination and 0 case with liver cirrhosis.
Situation of colon cancer patients' hepatic metastases with hepatitis B virus
- The situation of 306 cases colon cancer patients collected in this research with or without hepatitis B does 2 half-and-half on the occurrence of hepatic metastases is shown in [Table 4]a
- During the process of recovery after being affected by HBV, hepatitis B does 2 half-and-half could present following situations: (a) the 1st item positive; (b) the 1st and 3rd items positive; (c) the 1st and 3rd and 5th items positive (health risk appraisal); (d) the 1st and 4th and 5th items positive (HBeAb positive); (e) the 2nd and 4th and 5th items positive; (f) the 4th and 5th items positive. The situations above in this research were called a joint name of hepatitis B positive with infection. For those who had injected HBV vaccine and been cured successfully or for those who had recovered successfully from infection of HBV and produced antibody themselves with the 2nd and 5th items positive or the 2nd item positive, these two situations were called a joint name of hepatitis B positive with vaccine [Table 4]b.
|Table 4a: Influence of states of hepatitis B does 2 half-and-half on hepatic metastases in colon cancer patients|
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|Table 4b: Situations of states of hepatitis B does 2 half-and-half on hepatic metastases in colon cancer patients|
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The study took a further analysis about the relevance between situations of hepatitis B does 2 half-and-half and the colon liver metastases, and the conclusion was that comparing the colon cancer patients whose five items of hepatitis B does 2 half-and-half were all negative with the positive subgroup, the risk of hepatic metastases of the former was 3.515 times higher, χ2 = 12.274, P< 0.001; the result is shown in [Table 5]a.
|Table 5a: Relevance of states of hepatitis B does 2 half-and-half and colon liver metastases|
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Then, this study took a further comparison between the different subgroups of the colon cancer patients with hepatitis B does 2 half-and-half all negative and two subgroups of hepatitis B does 2 half-and-half positive (positive with infected and positive with vaccine). The group of positive with infected was as Group A, and the group of positive with vaccine was as Group B. The result is shown in [Table 5]b and [Table 5]c.
|Table 5b: Relevance of state of hepatitis B does 2 half-and-half and colon liver metastases|
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|Table 5c: Relevance of state of hepatitis B does 2 half-and-half and colon liver metastases|
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The logistic multifactor regression analysis about colon cancer patients' hepatic metastases
The study put patients' multifactor including gender, age, part of primary focus (intestine segment), size of cancer, depth of infiltration (T-stage), differentiated degree, and regional metastasis of lymphonodus and basic liver diseases into logistic regression analysis to see whether there were independent risk factors that influence the hepatic metastases. The results are shown in [Table 6]. Besides, this research did not see hepatic metastases in eight cases of patients: Four of whom were with liver cirrhosis and the other four with subtype of mucinous adenocarcinoma. However, the subgroups' cases above were too less to be unbiased, so they were not included in the multifactor analysis for the moment. We were about to analysis it further more in discussion.
|Table 6: Multifactor logistic regression analysis of colon liver metastases|
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| » Discussion|| |
As we know, the colon cancer is one of the most common malignant tumors in the world. Colorectal cancer and its hepatic metastases have become one of the main reasons that cause death. The rate of hepatic metastases is higher than other malignant tumor in the enterocoelia and other organ. In this study, 40 of the 306 cases of colon cancer patients in this research had hepatic metastases, with a proportion of 13.1%. The data and situation about the rate of hepatic metastases were similar to other scholars'. As shown in [Table 1], there was a trend that male patients were more than female. Young patients (under age 60-year-old) showed a trend that the rate of hepatic metastases was higher at advanced age. However, according to the statistical analysis, they did not have significant difference. In the aspect of parts of primary focus, its single-factor Chi-square analysis had the statistical significance; however, in a further step of multifactor logistic regression analysis, there was no statistical significance. Hence, patients' gender, age, part of primary focus in intestinal segment, size of cancer were not as the independent influence factors on liver metastases in this research, as the same to scholars many papers reported by other scholars.,
At the meantime, the majority of scholars showed that the differentiated degree had significant relevance with liver metastases., Other reports showed that there was no statistically significant difference between the differentiated degree of intestinal cancer and liver metastases. In this research, the single-factor Chi-square analysis showed that colon cancer patients' rate of hepatic metastases had significant relevance with cancer's differentiated degree. However, in the further multifactor logistic analysis, there was no statistical significance. Hence, differentiated degree was not as the independent influence factors in this research. Considering the reasons that this research is a general retrospective study, it could not exclude the existence such as the insufficiency of cases, the single-center study. Hence, the correlation between differentiated degree and liver metastases could not be concluded finally.
In addition, this research showed the depth of infiltration (T-state) as an independent risk factor of the rate of hepatic metastases. This result was same as the majority of the research at present.,
In the aspect of serology, the statistics situation was similar to the aspect of differentiated degree. Taking a further observation, the average value of preoperative serum CEA level of the forty cases of patients with hepatic metastases was 245.803 ng/ml; the average value of preoperative serum CEA level of the 266 cases of patients without hepatic metastases was 14.080 ng/ml. The level of the former was much higher than that of the later. Thus, there might be certain links between two of them. By consulting the literature, some relative reports showed that there was significant correlation between patients' preoperative serum CEA level and the ratio of hepatic metastases.
In the aspect of lymphatic metastasis, the study did not find the significant correlation between lymphatic metastasis and hepatic metastases among the colon cancer patients. With the further observation, among the forty cases of patients with hepatic metastases, the amount of positive lymphonodus was up to 150 (the inspected number of lymphonodus was 754), 3.750 for each case, and the degree of lymphatic metastasis was 19.9%; among the 266 cases of patients without hepatic metastases, the amount of positive lymphonodus was 503 (the inspected number of lymphonodus was 6422), 1.891 for each case, and the degree of lymphatic metastasis was only 7.8%. It showed that the amount of positive lymphonodus of patients who were with hepatic metastases in the subgroups was much higher than those who were not with hepatic metastases. By consulting the literature, some relative reports showed that there was significant correlation between the situation of lymphatic metastasis and the ratio of hepatic metastases. Those who had lymphatic metastasis had higher ratio of hepatic metastases than the other.
Besides, according to the classification by WHO, colon cancer are often seen as canalicular adenoma in histopathology. In this study, the major type of pathological primary focus was canalicular adenoma, which occupied 302 of 306 total cases, while only four cases belonged to mucinous adenocarcinoma. It matched WHO's relative situation well. All of the forty cases colon cancer patients with hepatic metastases belonged to pathologic subtype of canalicular adenoma. Taking a further analysis on the four cases of colon cancer patients who were with pathologic subtype of mucinous adenocarcinoma, two of them were in IIIb state when first diagnosed, two in IV state; one was with severe fatty liver, three were with hepatitis B does 2 half-and-half. The causes that these four cases of colon cancer patients with pathologic subtype of mucinous adenocarcinoma did not occur hepatic metastases at present, might be to that the cases were too tiny to be unbiased, and meanwhile might be influenced certainly by hepatic underlying disease. Hence, the research could not put out the reliable results. However, by consulting the relative literature, the scholars reported that there was no significant correlation between the pathologic type of colorectal cancer and hepatic metastases. At the same time, there were reports already that the patients' ratio of hepatic metastases who were with liver cirrhosis was lower than the others., Then, the study took a further observation about the influence of hepatic underlying disease on the metastases of colon cancer. There were twenty cases of colon cancer patients with fatty liver in this research and eight of them had the positive hepatitis B does 2 half-and-half at the same time. Only two cases of patients with fatty liver had the liver metastases; and in the 8 cases of positive hepatitis B does 2 half-and-half, there was no case with liver metastases. The statistical analysis showed that there was no significant correlation between hepatic metastases and fatty liver underlying disease in colon cancer patients. Anyway, some researches showed that fatty liver could cut down the ratio of liver metastases. Those results did not match this study. The cause might be to the tighty cases of fatty liver in this study (with a proportion of only 6.5% in total).
In this research, we found that states of hepatitis B does 2 half-and-half were meant to have significant correlation with hepatic metastases in colon cancer patients, and it was also the independent risk factor to hepatic metastases. By statistical analysis, compared with subgroup of hepatitis B all negative, the both two subgroups of hepatitis B positive with infection and with vaccine both showed statistically significant (P = 0.011 and 0.004). However, as a result of this paper belonged to general retrospective study, the sample into the group might be not enough, and the results might be biased. By consulting the literature, some relative reports showed that the ratio of liver metastasis in colon cancer patients was reduced significantly by hepatitis B or hepatitis C virus infection (8.1% vs. 21.1%)., It could be thought that HBV infection had effects on the incidence of liver metastasis in colon cancer patients. The background of HBV infection might be one of the protective factors on liver metastasis. As to the reasons, it might be associated with the liver cell immune mechanism activated by viral infection. As we knew, the body had many Kupffer cells in hepatic sinus endothelial cells; in fact, that was the liver fixed phagocytes, having the effect that could eliminate or reduced antigenicity. Moreover, the cells of tumor being defensed and removed relied to immune cells. Existing research showed that the activation of Kupffer cells could promote the apoptosis of experimental liver cancer cells. The phagocytosis and phagocytic cells could also produce some immune adjustment factors as well, such as interferon and interleukin (IL). Moreover, the Kupffer cells could also produce IL-6, which could promote the storage of fat cells appreciation, increase liver extracellular matrix synthesis, and lead to the collagen deposition in the liver. It even might lead to liver fibrosis, so to inhibit the formation of metastatic carcinoma, which did not benefit the growth and engraftment of tumor metastasis in liver cells. This explained that the seven cases with liver cirrhosis never had liver metastasis in this study in a certain. Moreover, it was just confirmed by the laparotomy results reported by Gervaz et al. Hence, this study suggested that the hepatitis B positive could reduce the incidence of liver metastases in colon cancer patients.
| » Conclusions|| |
The infiltration depth and the states of hepatitis B does 2 half-and-half were the independent risk factors on colon cancer patients' hepatic metastases. Those with the infiltration depth of T4 had a higher rate of hepatic metastases. Patients with does 2 half-and-half positive hepatitis B (whether subgroup of HBV infection or subgroup hepatitis B vaccine-related) had a lower incidence rate of liver metastasis than those with hepatitis B all negative.
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Conflicts of interest
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9]