colon cancer
Introduction
Introduction to colon cancer Colon cancer is a common malignant tumor of the digestive tract, accounting for the second place in the gastrointestinal tumor. The predilection site is the junction of rectum and rectum and sigmoid colon, accounting for 60%. The incidence is more than 40 years old, and the ratio of male to female is 2:1. basic knowledge The proportion of sickness: 0.0026% Susceptible population: After the onset of 40 years old, the ratio of male to female is 2:1. Mode of infection: non-infectious Complications: anemia
Cause
Cause of colon cancer
Risk factor
Clinically, certain factors may greatly increase the risk of morbidity. They include:
1. Age of onset, most patients develop after 50 years of age.
2, family history: If a person's first-degree relatives, such as parents, have had colorectal cancer, he is 8 times more likely to suffer from this disease in his lifetime than the general population, about a quarter of new patients Have a family history of colorectal cancer.
3, history of colon disease: some colon diseases such as Crohn's disease or ulcerative colitis may increase the incidence of colorectal cancer, their risk of colon cancer is 30 times that of ordinary people.
4. Polyps: Most colorectal cancers develop from small precancerous lesions. They are called polyps. Among them, villus-like adenomatous polyps are more likely to develop into cancer, and the chance of cacao becomes about 25%. Tubular adenocarcinoma The polyposis rate is 1-5%.
5, genetic characteristics: some familial tumor syndrome, such as hereditary non-polyposis colon cancer, can significantly increase the incidence of colorectal cancer, and the onset time is younger.
Some colon cancer epidemiological studies have shown that social development status, lifestyle and dietary structure are closely related to colon cancer, and there are phenomena suggesting that there may be differences in the environment and genetic factors affecting the incidence of colon cancer in different parts and age groups. Environment (especially diet), genetics, physical activity, occupation, etc., are possible etiological factors affecting the incidence of colon cancer.
Dietary factors (30%):
Epidemiological studies have shown that 70% to 90% of cancer incidence is related to environmental factors and lifestyle, and 40% to 60% of environmental factors are related to diet and nutrition to some extent, so diet in the onset of cancer Factors are seen as extremely important factors.
1, high-fat, high-protein, low-cellulose mechanism of action: can be summarized as follows: 1 affect intestinal lipid metabolism, high-fat diet increased 7a-dehydroxylation enzyme activity, resulting in increased secondary bile acid formation, while fiber The effect of the element is opposite, and by inhibiting reabsorption, dilution and adsorption, chelation, reducing the deoxycholic acid concentration in the intestine, increasing the solid phase material in the feces and promoting the discharge; some dietary factors (such as calcium ions) can reduce the intestinal tract. The levels of ionized fatty acids and free bile acids, both of which have an damaging effect on the intestinal epithelium; inhibit the degradation of intestinal cholesterol. Milk, lactose and galactose have the effect of inhibiting the redox effect of cholane. 2 Cellulose also has the effect of changing the intestinal flora, affecting the structure and function of intestinal mucosa, affecting the growth rate of mucosal epithelial cells, mediating the pH of the intestine, and strengthening the mucosal barrier through mucin to reduce intestinal toxic substances to the intestine. Invasion of the epithelium; 3 high fat and some carbohydrates can increase the activity of intestinal cell enzymes (such as glucuronidase, ornithine dehydrogenase, nitroreductase, azolasin, lipoxygenase, cyclooxygenase) ), promote the production of carcinogens and auxiliary cancers. 4 The effect of biological macromolecular activity. When the cytoplasm is acidified, DNA synthesis is inhibited and the cell cycle is prolonged.
2, vitamins: case-control study showed that carotene, vitamin B2, vitamin C, vitamin E are related to the reduction of the relative risk of colon cancer, and a dose-response relationship. Vitamin D and calcium have a protective effect.
3, onion and garlic: onion and garlic foods have been widely concerned about the protection of the body, and in the experiment repeatedly confirmed the inhibition of this type of food on tumor growth. Garlic oil can significantly reduce colonic mucosal cell damage caused by dimethyl cholestyramine, and can reduce the colon cancer induction rate of mice by 75%. According to the case-control study, the risk of colon cancer in high-intake garlic foods was 74% in the low-intake group.
4. Salt and preserved foods: The relationship between salt content and gastric cancer, colon cancer, and rectal cancer. In the high salt intake group, the relative risk of the three cancers increased. The case-control study suggested that the weekly intake was 3 The excess risk of colon cancer in the above-mentioned cured foods was 2.2 times (P<0.01) for less than one time, 2.1 times for left colon cancer, and 1.8 times for right colon cancer. The explanation for this risk factor may be related to the carcinogens produced during the food pickling process, and high salt intake may be a concomitant state.
5, tea: tea polyphenols is a strong antioxidant, can inhibit the carcinogenic effect of carcinogens. According to the case-control study, the risk of rectal cancer in drinking tea (green tea or black tea) more than 3 times per week was 75% of that of less than one, but not related to the colon cancer group. In the past 10 years, the study suggests that there is a significant negative correlation between tea drinking and the risk of colon cancer, but there are also reports of the opposite. Because of the small number of studies on the protective effect of tea drinking on colon cancer prevention, it is difficult to evaluate the role of tea drinking in the pathogenesis of human colon cancer. The relationship between coffee and colon cancer is still difficult to determine.
6. Trace elements and minerals: 1 Selenium: The mortality rate of various cancers (including colon cancer) is negatively correlated with local dietary selenium intake and soil selenium content. It is speculated that selenium and potassium are associated with a low risk of colon cancer. However, it is believed that these factors may be just some accompanying factors, and do not directly affect the risk of colon cancer in the population. 2 Calcium: Animal experiments have shown that calcium can improve the toxic effects of deoxycholic acid on intestinal epithelium. Some scholars believe that the increase of the concentration of bile acids and free fatty acids in the intestine can promote the occurrence of colon cancer, and calcium can be combined with them to form insoluble saponified compounds, so that their effects on intestinal epithelial stimulation and toxicity are alleviated. Some epidemiological studies have also suggested that calcium intake can prevent the development of colon cancer.
Occupational factors and physical activity (20%):
Insulated asbestos production workers are more common in colon cancer patients, and animal experiments have shown that swallowing asbestos fibers can penetrate the intestinal mucosa. In addition, the metal industry, cotton yarn or textile industry and leather manufacturing. It has been confirmed that in the production process of plastics, synthetic fibers and rubber, a compound which is often used - acrylonitrile has a role in inducing the stomach, central nervous system and breast tumors, and textile workers exposed to the substance, lung cancer and colon The incidence of cancer is high. Despite this, colon cancer is generally not considered an occupational disease.
In the analysis of occupational physical activity, it is found that the risk of colon cancer in long-term or frequent sitting is 1.4 times that of some major physical activity, and it is more closely related to cecal cancer. As a result of case-control studies, moderate-intensity physical activity has a protective effect against colon cancer, especially colon cancer.
Genetic factors (20%):
It is estimated that genetic factors may play an important role in at least 20% to 30% of colon cancer patients, including 1% of familial polyposis and 5% of hereditary polypoid-free colon cancer syndrome. 80% to 100% of patients with hereditary familial polyposis may develop malignant tumors after 59 years of age. In addition, patients with familial colonic polyposis have a majority of left colon cancer, while patients with hereditary nonpolyposis often have right colon cancer.
Through the case-control pedigree survey of the whole population (1328 cases of colon cancer probands and 1451 population control families), the results showed that the prevalence of colon cancer in the first-degree relatives of different proband groups was significantly higher than that of the second-degree relatives. The age at diagnosis of colon cancer proband is related to the risk of colon cancer in the first-degree relatives. The younger the proband is, the greater the relative risk of colon cancer in the first-degree relatives of the family, the first-degree relatives of the colon cancer 40 years old. The relative risk is six times that of the >55 age group. Family members (first-degree relatives) with a family history of colon cancer, especially those with a colon cancer age of 40 years or younger, should be given high priority.
Disease factor (10%):
1, intestinal inflammation and polyps: intestinal chronic inflammation and polyps, adenoma and suffering from extensive ulcerative colitis for more than 10 years: the risk of colon cancer is several times higher than the general population. Patients with ulcerative colitis with severe dysplasia have a 50% chance of developing colon cancer. Clearly, patients with ulcerative colitis are at higher risk of developing colon cancer than the general population. The data in China suggest that the risk of colon cancer in patients with onset of disease for more than 5 years is 2.6 times higher than that of the general population, but not closely related to rectal cancer. For patients with limited and intermittent lesions, the risk of colon cancer is small.
Crohn's disease is also a chronic inflammatory disease that invades the small intestine and sometimes the colon. A growing body of evidence suggests that Crohn's disease is associated with colon and small bowel adenocarcinoma, but to a lesser extent than ulcerative colitis.
2. Schistosomiasis: According to the retrospective investigation of cancer deaths in Zhejiang Province from 1974 to 1976 and the survey data of Chinese malignant tumors from 1975 to 1978 and the Chinese schistosomiasis atlas, the relationship between schistosomiasis endemic areas and colon cancer incidence and mortality was discussed. Correlation. There is a very significant correlation between the incidence of schistosomiasis and the mortality rate of colon cancer in 12 counties and autonomous regions in southern China and 10 counties in Jiaxing, Zhejiang Province. It is suggested that in areas where schistosomiasis is seriously endemic in China, schistosomiasis may be associated with high incidence of colon cancer. However, there is little evidence from epidemiological studies about colon cancer and schistosomiasis. For example, in Jiashan County, Zhejiang Province, which is increasingly controlled by schistosomiasis, the mortality rate of colon cancer and the incidence of schistosomiasis in this area have been the highest in China, and the infection rate of schistosomiasis has decreased significantly. However, according to recent survey results, epidemiological and pathological studies of colon polyp carcinogenesis also suggest that polyp carcinogenesis has nothing to do with the presence or absence of schistosomiasis eggs in polyps. In addition, the results of the colon cancer screening conducted in the above two regions do not support schistosomiasis as a risk factor for colon cancer. In the case-control study, no history of schistosomiasis was found to correlate with colon cancer.
3, cholecystectomy: In recent years, there are about 20 literatures in China about the relationship between cholecystectomy and colon cancer. Some of these studies have shown that after cholecystectomy can increase the risk of colon cancer, especially proximal colon cancer. Men have an increased risk of colon cancer after cholecystectomy; in contrast, women have a lower risk of developing rectal cancer after the procedure. There are also views that the effect of cholecystectomy on female colon cancer is greater than that of men.
It is generally believed that the occurrence of tumors is the result of a combination of factors, and colon cancer is no exception. Colon cancer, as a disease closely related to the lifestyle of Western society, is closely related to its etiology, and it is considered that the role of dietary factors is the most important. The etiology of high fat, high protein, high calorie and lack of cellulose intake is still dominant, and most of the results are consistent with this model. Other carcinogenic factors have relatively weak effects, such as disease factors, genetic factors, and occupational factors. It can be considered that the carcinogenic process of colon cancer is based on the role of dietary factors, combined with the results of multiple links of other factors. With the deepening of etiology and the penetration of multidisciplinary, there is now a new understanding of the carcinogenic mechanism of colon cancer. In the field of epidemiology, modern technology is more widely used, and some factors that are not consistent with previous results are more deeply understood, and the possible causes of epidemiological results will be further clarified.
Pathogenesis
1, pathogenesis
Based on modern biology and epidemiological research, it is increasingly clear that colon cancer is the result of synergy between environment, diet and living habits and genetic factors. The role of carcinogens combined with cellular genetic background leads to cytogenetic mutations and gradually develops into cancer. Because of the long-term pathogenesis of colon cancer, and some have obvious stages of precancerous lesions of adenoma, colon cancer has become an ideal model for studying the pathogenesis of tumors and the pathogenesis of malignant tumors. In terms of etiology, in addition to genetic factors, other factors are classified into two categories according to the changes in cytogenetic, namely: genotoxic carcinogens and non-genotoxic carcinogens.
Colon cancer is formed by multiple factors and multiple stages, and various molecular events develop. Various factors can be classified into endogenous and exogenous factors, and the occurrence of tumors is the result of internal and external interactions. External factors are nothing more than physical and biological factors, genetic or acquired genetic instability, microsatellite instability and chromosomal instability. In the gradual development and progression of colon cancer, molecular events can be primary genetic events and secondary molecular events. The former is a mutation in the gene structure, and the latter is a change in gene expression during the development and evolution, and does not involve changes in gene structure, such as changes in protein, enzyme levels, and phosphorylation, acetylation or glycosylation in translational modifications. Malignant tumors are increasingly clear in the concept of a class of cytogenetic diseases. In the pathogenesis and pathogenesis of colon cancer, different genetic backgrounds have different susceptibility, which also determines the characteristics of colon cancer pathogenesis. The following three aspects describe the malignant transformation process of colon cancer.
(1) Malignant transformation process of colon cancer: the malignant transformation process is the whole process of primary genetic events, and a group of genotoxic carcinogens, ie, carcinogen promoters, initiates multiple attacks on cells, resulting in DNA mutations occur in the corresponding genes, and the genotype changes, leading to genetic transformation of the cells - cancer. In colon cancer, morphologically, its phenotype includes epithelial hyperplasia, adenoma formation, carcinoma in situ, and invasion and metastasis of cancer.
Some colon cancers are derived from adenomas. Adenomas may undergo a long period of time from the onset to the formation and associated with atypical hyperplasia, which is beneficial for observation and research. Therefore, more oncogenes and tumor suppressor genes involved in molecular events have been discovered. . The APC gene (adenomatous polyposis coli) and c-myc gene are the primary genetic events involved in the adenoma stage.
Cancerous changes occur in adenomas, but also in flat mucosa. Molecular events of hyperplasia of the epithelium include genes related to the adenoma stage, involving a total of at least 9 to 10 gene molecular events, which can be summarized as dominant Oncogenes and recessive anti-cancer genes 2 major categories.
1 dominant proto-oncogene: generally a positive regulator of normal cell growth, a single allelic mutation is sufficient to cause a change in cell phenotype, ie, genetic structure changes. Even if the gene is mutated only on a single chromosome, its phenotypic change can be caused.
Ac-myc gene: is a pre-adenomas mutated gene, located in the 8q24 segment, about 70% of colon cancer, especially in the left colon cancer, c-myc overexpression can be several to dozens of times. Its expression level is also high in normal cells with fast growth, which indicates that it plays an important role in regulating cell proliferation. The APC gene is intrinsically linked to the overexpression of c-myc. None of the c-myc mutants have APC gene loss, and the c-myc gene also has the function of regulating the ras gene.
B.Ras gene: colorectal adenoma larger than 1cm adenoma has a 50% chance of detecting point mutations in at least 1 of the Ras gene family (H-ras, K-ras and N-ras), at <1cm The point mutation is about 10%, and the mutation rate is directly related to the degree of atypical adenoma. It can be used as a signal for adenoma with malignant potential. Therefore, the degree of malignancy and the prognosis are estimated by the mutation detection rate. The vast majority of ras gene mutations occur in the 12th and 13th codons of the Ki-ras gene, accounting for 88% of all mutant codons, and the other common site is the 61st codon. In the Chinese colon cancer study, the two cell lines HR8348 and Hce8693 were the 12th codon of Ki-ras, and the second GC base was converted. In 37 cases of Chinese colon cancer cells, 37% have Ki-rar gene fragments, and China has successfully detected the mutant Ki-ras gene fragment in the feces of 33.3% (6/18) colon cancer patients by non-radioactive nuclides. Provides possibilities for molecular diagnosis.
2 Receptive tumor suppressor gene: a negative regulator, when a single allele is deleted or mutated, the corresponding gene on the other chromosome can still maintain its normal function of the normal phenotype, only in the 2 alleles In the absence or mutation, the dysfunction of the gene, phenotypic changes, resulting in uncontrolled cell proliferation and canceration.
A. APC gene: The APC gene was first discovered in the familial adenomatous polyposis (FAP) and cloned at 5q21. FAP is autosomal dominant syndrome, FAP can be associated with extra-colonary lesions, such as Gardner syndrome with bone disease or fibrosis, Turcot syndrome with brain tumor, genetic deletion of chromosome 5q21, allele loss (loss of heterozygosity). Loss of this gene is also present in 35% to 60% of patients with no family history of colon cancer.
B. Mutation of the MCC (mutated in colorectal cancer) gene: The MCC gene is also located at 5q2l, which is close to the APC gene locus, and there are structurally similar fragments in the structure. However, there are few MCC gene mutations in the FAP family, and about 15% of sporadic colon cancers are inactivated by somatic mutations, and mutations occur on GC base pairs (GCAT).
C. DCC (deleted in colorectal cancer) gene deletion or mutation: about 50% of late adenomas and more than 70% of colon cancers can be detected with loss of heterozygosity in the chromosome 18q21 region. That is, the DCC gene is a large gene, which is more than 70kD. Its function has not yet been completely determined. The inactivation of DCC gene in colon cancer is likely to cause the recognition of extracellular information molecules from other cells, extracellular matrix or soluble molecules. Change to obtain some malignant phenotypes.
D.p53 gene: The human p53 gene is located on the short arm of chromosome 17 (17p13.1) and is 16-20kD long. It consists of 11 exons and encodes a nucleoprotein of 393 amino acids. Its molecular weight is 53kD. And got its name. It is currently the most studied tumor suppressor gene and is generally associated with various types of tumors. Chromosome 17 short arm allele loss (17p) occurs in 75% of colon cancers, but is rare in adenomas. The naturally occurring wild-type p53 (WT-p53) gene maintains normal cell cycle and regulates cell cycle progression. In recent years, there have been many studies on apoptosis. Apoptosis, also known as progressive programmed cell death, is a mechanism of cell self-destruction. It can counteract the accumulation of abnormal cells during tumor formation, so inhibition of apoptosis will lead to tumorigenesis. WT-p53 is involved in the induction of apoptosis. WT-p53 is mutated, rearranged, translocated in most tumors, and its p53 protein function is inhibited. Inactivation of WT-p53 causes the proliferation of colorectal mucosal epithelial cells to become cancerous.
In primary genetic events, genes involved in colon cancer include dominant oncogenes and recessive negative regulatory tumor suppressor genes. For example, according to their function, they can be classified into two categories, namely genes related to the replication signaling pathway and guarantees. The genes correctly replicated by DNA, the former are Ki-ras, APC and DCC, and the latter are hMSH2, hMLH1, hPMS1, hPMS2 and p53. At present, we can see the understanding of the mechanism of action of various genes.
(2) The malignant evolution process of colon cancer: the malignant evolution, that is, the diffusion process of tumor invasion and metastasis, that is, the secondary molecular event, is the result of the gene expression product. Under the action of these substances or factors, the growth of carcinoma in situ is out of control, and it is infiltrated, spread and metastasized from normal cells or surrounding cells, leading to a malignant progression. The progression of colon cancer is similar to that of other tumors and can have the following major changes:
1 Colon cancer cells overgrow and get rid of normal growth patterns. This process includes functional changes such as growth factors, protooncogenes, and metastasis suppressor genes. It has been confirmed that colon cancer cells can produce angiogenin and basic fibroblast growth factor (b-FGF), transforming growth factor alpha and (TGF-, TGF-), synergistic, enriches blood supply, and provides conditions for rapid tumor growth.
2 The related receptors of cancer cells adhering to the basement membrane and matrix molecules are changed. The infiltration of cancer cells firstly contacts the cells and attaches to the basement membrane, penetrates to reach the surrounding matrix, and then moves to the outer wall of the blood vessels and enters the blood vessels, depending on the components. Receptor-ligend interaction between receptors. In the interaction between the binding proteins on colon cancer cells and normal epithelial cells and matrices, the relevant binding proteins are identical, only the difference in expression levels, there is a specific protein in the attachment of colon cancer cells to the basement membrane and matrix molecules. Body: A. Non-integrated laminin binding protein; molecular weight 67kD protein, exists in the bottom cell membrane, and has high affinity with laminin. Another protein has a molecular weight of 32 kD and also has high affinity. Both of these binding proteins have increased expression in colon metastatic carcinoma and are associated with Dukes stage progression. B. Integrin: is a family of cell surface receptors composed of a combination of and peptide chains, which can specifically bind to laminin, collagen and fibronectin, and mediate cells. - A group of receptors for cells, cells, and extracellular matrices that are involved in cell growth, differentiation, formation of junctions, and cell polarity. C. lectin: The molecular weight of the protein that specifically binds to sugar or oligosaccharide is 31kD, which is significantly elevated in cancer cells, and is not expressed in benign tumors. It is significantly correlated with serum CEA levels, and is also associated with tumor progression. Consistent. In addition, the related receptor CD44 in lymphocytes is also expressed in epithelial cells, which are divided into epithelial cell type and lymphocyte type CD44, which are the main receptors for the recognition of hyaluronidase, and can also bind to the basement membrane and matrix proteins. CD44 is significantly higher in colon cancer than in adjacent normal mucosa.
3 from the basement membrane and matrix, cancer cells immersed in the bloodstream or lymphatic flow, constitute infiltration and metastasis: the change of proteases is the basis of its molecular events, colon cancer cells can be autocrine protease: A. type IV collagenase: colon cancer at least It can produce three kinds of collagenases with molecular weights of 64kD, 72kD and 92kD, which can be higher than normal mucosa, can degrade type IV collagen, fibrin and laminin, but can not degrade type I and type III collagen in interstitial. . B urokinase: is a plasminogen activator, colon cancer can secrete urokinase, its production is negatively correlated with tumor differentiation, and colorectal adenoma and cancer are higher than normal.
4 The tumor cells are directly inoculated on the surface of the cavity after detachment, and the molecular changes are: colon cancer cells secrete a kind of ligand, which binds to receptors of the lining cells of the epithelial space involved in metastasis, thereby forming planting, ligands including cancer cells. Antigen, mucus or blood group antigen.
(3) Genetic susceptibility of colon cancer: Due to external factors and genetic background, the occurrence and development of malignant tumors objectively formed some high-incidence populations or susceptible populations.
1 Deletion or mutation of colon cancer suppressor gene: tumor suppressor gene mutation, corresponding cell growth and detachment regulation, resulting in cancerous growth, in the colon cancer, APC, DCC and p53 and other tumor suppressor genes are deleted, highly susceptible to carcinogens The blows formed a group of susceptible populations, such as familial adenomatous polyposis (FAP) and Gardner syndrome (GS) family members, all of which are potential colon cancer susceptibility. In 1985, Herrer found that 5q13~15 and 5q15~22 were partially missing in a patient with GS. In 1981, Solomon found that the lymphocyte allele was absent in patients with sporadic colon cancer, ie APC and MCC. The APC gene mutation occurred in 60%~ 87% of patients with FAP and GS. MCC mutations were only found in sporadic colon cancer with a mutation of approximately 15%. The APC gene mutation is the earliest molecular event currently detectable in somatic cells. Dry Moon Wave et al. (1994) detected 2 cases of APC gene mutations in FAP pedigree members in Chinese peripheral lymphocytes (22 years old and 24 years old). Two cases of FAP patients confirmed by fiber enteroscopy, so screening can be applied to families with genetic background for early detection, which is an effective measure for early treatment.
2 DNA damage repair system defects: According to genetic epidemiological studies, colon cancer has a family agglomeration phenomenon, in addition to FAP and GS, hereditary nonpolyposis colon cancer (HNPCC) accounts for 3% to 30% of colon cancer %. In recent years, six genes have been found to be associated with HNPCC. The hMLH1, hMSH2, hPMS1, hPMS2, hMSH3 and GTBP/hMSH6 genes can be isolated from this family, and compared with the DNA mismatch repair system in E. coli and yeast. . Mutations in any of the genes in the system result in defects or loss of cell mismatch repair function, resulting in increased accumulation of various spontaneous or non-spontaneous mutations in the cell, which in turn leads to replication errors and genetic instability. Recent studies have found that there is genetic instability in most HNPCC patients, manifested as replication error (RER), a single or 2 to 6 nucleotide repeat in genomic DNA. The length of the sequence has changed. According to the literature, the positive rate of RER in colon cancer of HNPCC patients is as high as 86%-100%, and the positive rate of RER in extra-colonal malignant tumors is 100%, while the positive rate of general sporadic colon cancer is only 12% to 16%, the two have significant differences. Combined with the study of mismatch repair system in E. coli and yeast, it is thought that the defect or loss of DNA mismatch repair function caused by mutation of mismatch repair gene (MMR) is the main cause of replication error, and thus may also It is the main cause of HNPCC.
3 genetic instability and susceptibility to colon cancer: HNPCC is a common autosomal dominant hereditary disease. In general, HNPCC includes the following two types: one is hereditary site-specific colon cancer (HSSCC), also known as LynchI syndrome. At least 3 of the two generations have colon cancer, at least 1 of which occurred before the age of 50. These patients have an earlier onset age than normal colon cancer, 70% of which are located in the proximal colon; It is a cancer family syndrome (CFS), also known as Lynch II syndrome. In addition to the characteristics of HSCC, it also shows a high incidence of colorectal malignant tumors. The most common is endometrial cancer, and other stomachs. Transitional cell carcinoma of the small intestine, ovary, adenocarcinoma of the biliary system and the urinary system.
Using a variety of microsatellite markers, extensively (3/11) of HNPCCs have been found to have erroneous repetitive DNA sequences such as single to four nucleotide repeats (CA) n or (CAG)n in HNPCC linkage analysis. It has also been found in colon cancer, but the number is small (6/46), suggesting frequent errors in the development of colon cancer, suggesting its genetic instability, and is also a group of susceptible people. Regardless of whether (CA)n, (CAG)n is the cause or the result, its appearance and existence show its susceptibility characteristics.
The idea that HNPCC is involved in mutations in mismatch repair genes has been confirmed by more and more studies. Most scholars believe that mutations in mismatch repair genes are early events in the process of carcinogenesis. According to Vogelstein's colon cancer model, tumorigenesis is a multi-gene, multi-stage process involving the inactivation of many tumor suppressor genes and the activation of oncogenes. The relationship between the mutation of the mismatch repair gene and the changes of these genes, and how it ultimately leads to the formation of cancer, the mechanism is still unclear. It has been reported that in colon cancer patients, genetic instability caused by defects in mismatch repair function causes colonic epithelial cells to lose response to TGF-mediated growth inhibition mechanism, thereby promoting tumor formation. But this is only one of the possible mechanisms, and further research is still needed. The solution of these problems can help us to understand the occurrence and development of HNPCC more clearly, so as to help subclinical diagnosis and early diagnosis by detecting certain genes, and to provide early intervention and treatment to reduce the incidence of HNPCC and improve the survival rate. .
(4) Colon cancer table (external) genotypic changes: gene expression function changes without coding gene structure changes to external (table) genetic changes.
1 Abnormal methylation and gene silencing in the regulatory region: There is a CpG island at the 5' end of the genomic regulatory region of the gene, that is, a small CpG accumulation region. The discovery of promoter methylation of the abnormal hMLH1 gene regulatory region in sporadic MSI colon cancer suggests a role for epigenetic alteration in tumor pathogenesis. Colon cancer tumor genomes have abnormal methylation, and gene silencing has been reported in multiple gene loci due to abnormal methylation in their promoters. Demethylating agents such as 5-deoxyazacytidine often restore the expression of these genes, suggesting that methylation is indeed responsible for the induction of gene silencing. The abnormality of hMLH1 methylation found in sporadic MSI colon cancer, the demethylation of cell lines established from this tumor can restore the expression of hMLH1, suggesting that this methylation disorder may be the cause of colon tumor formation. It is not the consequence.
Overexpression of 2c-myc gene: about 70% of colon cancer, especially in the left colon, the expression level of c-myc is several to dozens of times of normal colorectal mucosa, but not accompanied by c Amplification or rearrangement of the -myc gene. Erisman et al also demonstrated that half of the cases with loss of heterozygosity of the APC gene were associated with increased expression of c-myc, whereas none of the cases without increased c-myc expression had loss of heterozygosity for the APC gene. Thus there is an intrinsic link between overexpression of the c-myc gene and changes in the genetic events of the APC gene, followed by secondary molecular events in the latter.
With the development of cell molecular biology, the understanding of various molecular events of colon cancer has been deepened day by day, such as more research on wnt/-caterin and TGF- superfamily information transduction pathway. These are all new starting points and ideas for revealing the molecular mechanism of colon cancer.
2, pathology
(1) The site of colon cancer: Colon cancer can occur in any part from the cecum to the rectum. The incidence of left colon in China is high, but it is also reported that the incidence of right colon cancer in women with high incidence is higher. According to the statistics of 3147 cases of colon cancer in China, the colon cancer pathology research group (NCG) accounted for 82.0% of all colon cancers, and the incidence of rectal cancer was the highest. 66.9%, significantly higher than Europe, America and Japan, the latter accounted for only 35% to 48% of colon cancer. The colon cancer of other intestines was sigmoid colon (10.8%), cecum (6.5%), ascending colon (5.4%), transverse colon (3.5%), descending colon (3.4%), hepatic flexion (2.7%), and splenic flexion ( 0.9%). However, in recent years, domestic and foreign data suggest that the incidence of right colon is increasing, which may be related to changes in dietary habits. According to recent data from the National Cancer Prevention Office, the incidence of colon cancer in Shanghai has increased significantly, and colon cancer is more than rectal cancer.
(2) The general type of colon cancer: For a long time, the classification of colon cancer is quite confusing. In 1982, the Collaborative Group of Colon Cancer Pathology in China made systematic and detailed observations on surgical specimens of surgically resected colon cancer, and proposed colon cancer into four types. After more than 10 years of analysis and practice of a large number of clinical and pathological data in various regions of the country, this classification is simple, clear, easy to grasp, and can reflect the biological characteristics of the tumor to a certain extent, and was adopted by the National Anti-Cancer Association in 1991. As the normative classification of the general types of colon cancer in China, it is divided into four major types.
1 uplift type: Where the main body of the tumor protrudes into the intestinal lumen, it belongs to this type. The tumor can be nodular, polypoid or cauliflower-like bulge, with a clear boundary and pedicle or broad-based. The cut surface, the boundary between the tumor and the surrounding tissue is often clear, and the infiltration is shallow and limited. If the tumor surface is necrotic and shedding, an ulcer can form. The ulcer is shallow and the tumor looks like a disc, which is called a disc-shaped type, and is a subtype of a bulge type. The disc-shaped type is characterized by a disc-shaped bulge of the tumor to the intestine, a disc-shaped or elliptical shape, a clear boundary, a broad base, and a slightly depressed ulcer on the surface, and the bottom of the ulcer is generally higher than the surrounding intestinal mucosa. In the facet, the boundary between the tumor and the surrounding tissue is clear. Although the muscle layer of the intestinal wall at the bottom of the tumor is infiltrated by the tumor, it is still completely identifiable without being completely destroyed.
2 ulcer type: is the most common general type. A deeper ulcer forms in the center of this type of tumor, and the bottom of the ulcer extends deeper or beyond the muscle layer. According to the shape and growth of the ulcer, it can be divided into the following two subtypes:
A. Localized ulcer type: The ulcer has a crater-like appearance, and the central necrosis and depression form an irregular ulcer. The edge of the ulcer is a tumor tissue that is obviously bulged on the surface of the intestinal mucosa. The cut surface, the tumor boundary is still clear, but the deep infiltration of the intestinal wall, the local muscle layer more destruction disappears, the tumor often invades and the serosal or extraserosal tissue. Due to the traction of the tumor block and the contraction of the proliferative fibrous tissue in the main tumor area, the broken ends of the muscle layer can be lifted in a figure-eight shape, and the bottom of the ulcer is also increased. At this time, it is difficult to see from the front. The disc-shaped type is different, but if the cut surface is seen to disappear and the broken end is eight shaped, it is easy to determine the distinction.
B. Infiltrating ulcer type: The appearance of this type of ulcer is like a stomach ulcer. The tumor mainly infiltrates into the intestinal wall to thicken the intestinal wall, and then the central necrosis of the tumor forms a depressed ulcer. The ulcer is surrounded by a tumor tissue covered with intestinal mucosa, with a slightly sloped bulge. In the facet, the boundary of the tumor tissue is unclear. If the ulcer is deep, the local muscle layer can completely disappear. The main difference between the infiltrating ulcer type and the bulging ulcer type is that the latter has a crater-like appearance, and a cancer tissue surrounded by a levee-like bulge is surrounded by the ulcer.
3 infiltration type: This type of tumor is characterized by infiltration and growth to various layers of the intestinal wall. The intestinal wall of the lesion is thickened, and the surface mucosa folds are thickened, irregular or disappeared and flattened. There are many ulcers in the early stage, and superficial ulcers may appear in the later stage. If the tumor involves the entire circumference of the intestine, the intestine can be narrowed due to the annular thickening of the intestinal wall and the accompanying fibrous tissue hyperplasia, that is, the so-called ring-narrowing type in the past, at which time a narrowed ring is visible in the serosa. The tumor boundary of the cut surface is unclear, and the intestinal wall is thickened by the infiltration of tumor cells, but the structure of each layer is faintly discernible.
4 gel-like type: When a large amount of mucus is formed in the tumor tissue, the tumor section may be in the form of a translucent gel, which is called a gel-like type, and this type is found in mucinous adenocarcinoma. The shape of the gel-like type is different, and it can be in the form of a bulge, and it can also form an ulcer or mainly infiltrate.
The above-mentioned bulging type, disc type, localized ulcer type and infiltrating type, infiltrating ulcer type can be regarded as two different stages of development of the tumor. The bulge type is more common in the early stage of the tumor, and the infiltration is shallow. As the tumor volume increases, the center forms a deep and shallow ulcer, and at the same time, it penetrates deep into the intestinal wall, and the sputum presents a disc-like or localized ulcer-like appearance. The infiltrating ulcer type is often the late performance of the infiltrating type.
Among the above four general types, ulcer type is the most common. According to the pathological analysis of 3147 cases of colon cancer in China, ulcer type accounted for 51.2%, followed by uplift type 32.3%, infiltration type 10.1%, and gel type 5.8%. There is a certain correlation between the general type and the histological type: the proportion of high-differentiated adenocarcinoma in the uplift type is high, accounting for about 30%, and the ratio to poorly differentiated cancer is 3:1; the ratio of highly differentiated cancer to poorly differentiated cancer in ulcer type It is 1:1.16; while the infiltrating type is more common in poorly differentiated cancer, the ratio of the two is 1:1.84. The gel-like type is all mucinous cancer.
There is also a certain correlation between the general type and the location of the tumor. Tumors in the right colon are more common in the type of bulging and localized ulcers, while those in the left colon are more common in invasive type, and often cause ring narrowing of the intestine.
(3) Histological type of colon cancer: The histological classification of colon cancer is more uniform at home and abroad. China refers to WHO's colon cancer classification principle and combines domestic experience to propose the following classification principles:
1 papillary adenocarcinoma: all or most of the tumor tissue is papillary. The nipple can be slender or thick and short, and the part that infiltrates into the intestinal wall often shows that the nipple protrudes in the saccular gland cavity of different sizes. Usually the nipple has less interstitial. The epithelium covered by the surface of the nipple is mostly single layer or stratified, and the degree of differentiation of cancer cells is different. It has been suggested that the differentiation of cancer cells can be further divided into highly differentiated and poorly differentiated papillary adenocarcinoma. The authors believe that the biological behavior of the two is not significant, and there is no need for further classification. The literature reports that the incidence of papillary adenocarcinoma in the colorectal is 0.8% to 18.2%, with an average of 6.7%.
2 tubular adenocarcinoma: is the most common histological type of colon cancer, accounting for 66.9% to 82.1% of all colon cancer. The formation of glandular tubular structures by cancerous tissue is the main feature. According to the differentiation and abnormality of the main glandular structure, it can be divided into 3 levels:
A. Highly differentiated adenocarcinoma: All or most of the cancerous tissue has a glandular tubular structure. The differentiation of epithelial cells is more mature, and most of them are lining the glandular lumen. The nucleus is mostly located in the basal part, and there is secretion in the cytoplasm, sometimes showing goblet cell differentiation.
B. moderately differentiated adenocarcinoma: most of the cancerous tissues still have glandular tubular structures, but the glandular ducts are irregular in shape and vary in size and shape, or branched; a small number of tumor cells are arranged in solid nests or strips. The cancer cells are poorly differentiated and the abnormality is obvious. When the glandular structure is formed, the epithelium can be arranged into a pseudo-stratified layer, the nuclear position is uneven and overlapping, and can reach the apical apical, and the cytoplasm secretory mucus is reduced. The moderately differentiated adenocarcinoma is a common subtype of tubular adenocarcinoma, accounting for about 70% of tubular adenocarcinoma.
C. Poorly differentiated adenocarcinoma: The ductal structure of this type of tubular adenocarcinoma is not obvious, only a small part (below 1/3) has a glandular tubular structure, and the cell shape is more obvious. It does not form a region of the duct structure and is indistinguishable from undifferentiated cancer. The biological behavior and prognosis of this type of tubular adenocarcinoma is similar to that of undifferentiated carcinoma.
3 mucinous adenocarcinoma: This type of cancer is characterized by the secretion of a large amount of mucus by cancer cells and the formation of a "mucus lake." There are two types of histology commonly seen: one is an enlarged cystic gland tubular structure, the capsule is a large mucus, the inner wall of the cystic duct is lined with a well-differentiated single-layer columnar mucous epithelium, and some of the epithelium is filled with a capsule. The mucus is flat and even falls off. This type of mucinous adenocarcinoma can often be associated with a partial papillary adenocarcinoma or a highly differentiated tubular adenocarcinoma. Another histological manifestation is the floating piles of cancer cells in a large mucus lake. The cells are poorly differentiated, and the nuclei are large and the deep stains can be printed.
4 signet ring cell carcinoma: the tumor consists of diffuse into a ring of sign ring cells, does not form a glandular tubular structure. When there is less mucus formation in the tumor, the nucleus can be round, the cytoplasm is pink and lacks the characteristics of the signet ring cell, but the mucus stain can detect the mucus in the cytoplasm. Signet ring cell carcinoma can also be accompanied by a small amount of extracellular mucus.
In recent years, some scholars have proposed that both mucinous adenocarcinoma and signet ring cell carcinoma are classified as mucinous adenocarcinoma (or mucinous carcinoma), and the two histological structures of mucinous adenocarcinoma are named as highly differentiated and moderately differentiated mucinous (glandular) carcinoma. The signet ring cell carcinoma is a poorly differentiated mucinous (glandular) cancer. Lu et al. analyzed the pathological data of 459 cases of colorectal mucinous carcinoma collected by the National Colon Cancer Collaboration Group according to the above classification, and found that the 5-year survival rate of the three groups was significantly different. Some authors have also found in the actual work that the second type of mucinous adenocarcinoma is sometimes mixed with signet ring cell carcinoma and is difficult to distinguish between them. Therefore, this classification has to be further explored.
The percentage of mucinous adenocarcinoma in colon cancer varies widely from country to country. Zheng Shu et al collected 7 groups of data (including NCG data) reported in the past 10 years in China, totaling more than 7,000 cases. The incidence of mucinous carcinoma (including signet ring cell carcinoma, the same below) was 13.4% to 26.5%, with an average of 19.0%, far higher than Japan's and Europe's 4% to 10%. Mucinous cancer is more common in young colon cancer patients. According to domestic statistics, the incidence of mucinous carcinoma in young colon cancer patients in the <30-year-old group is 34.3% to 47.7%, especially in signet ring cell carcinoma. Only 12.3% to 19.3% of patients in the >30 age group.
5 undifferentiated cancer: cancer cells diffuse into pieces or agglomerate invasive growth, do not form ducts or other tissue structures. Cancer cells are usually small, with little cytoplasm, uniform size and shape, and sometimes difficult to distinguish from lymphosarcoma. At this time, they can be used for reticular fiber staining and immunohistochemical markers such as white blood cell common antigen (LCA), CER and keratin (Keratin). Identification. Undifferentiated cancer accounts for 2% to 3% of colon cancer.
6 adenosquamous carcinoma: also known as adenoid cell carcinoma, adenocarcinoma and squamous cell carcinoma components in such tumor cells are intermingled. If the squamous epithelial components are differentiated and mature, the adenocarcinoma is called squamous metaplasia and should not be called adenosquamous carcinoma.
7 squamous cell carcinoma: It is rare for squamous cell carcinoma to be the main component of colon cancer. If it occurs at the lower end of the rectum, it is necessary to rule out the possibility that the anal canal squamous cell carcinoma involves the rectum.
Adenosquamous carcinoma and squamous cell carcinoma account for less than 1% of colon cancer.
Colon cancers of the various tissue types described above have different biological properties. Well-differentiated carcinomas (including papillary adenocarcinoma) are predominantly propelled, and the leading edge of tumor infiltration often has more obvious host defense responses, such as lymphocytosis and fibrous tissue hyperplasia. The poorly differentiated cancer is mostly invasive, and the defensive response of the host of the tumor is not obvious. The authors found that the interstitial lymphocytic infiltration of mucinous adenocarcinoma is rare or absent, and there are few blood vessels, and the interstitial is mostly collagenized and hyaline. Therefore, it is believed that this type of stroma may be formed by tumor induction, not the body's defense response. which performed.
(4) Early colon cancer, adenoma carcinogenesis and paracancerous migration mucosa:
1 Early colon cancer and general type: Early colon cancer refers to the infiltration of cancer into the submucosa without involving the muscularis. If the tumor range is limited to the mucosal layer and does not involve the mucosal muscle layer, it is called intramucosal cancer. Because there are few lymphatic vessels in the colonic mucosa, such early cancers generally do not metastasize. Based on this phenomenon, some scholars advocate that there is no intramucosal cancer in the colon, so-called intramucosal cancer should be classified as adenoma. The lymph node metastasis rate of early colon cancer involving the submucosa is 5% to 10%.
The general type of early colon cancer is similar to that of early gastric cancer. It can be divided into the following three types: A. Polypoid type (type I): The tumor protrudes to the surface of the intestinal mucosa, forming a long pedicle, short pedicle or broad-based bulge. This type of tumor is mostly intramucosal cancer. B. Flat bulge type (type II): The naked eye looks like a coin, and the micro-bump is on the surface. This type is also mostly intramucosal cancer. C. Flat bulge with ulcer type (type III): the eye is like a small dish, the central dimple forms an ulcer, and the edge is slightly raised. This type is mostly submucosal cancer.
About 75.5% of early cancers occur in the rectum, which may be easier to check with the rectum than other intestines, and lesions are easier to detect. 0.5 to 6 cm, the volume > 2 cm is mostly submucosal cancer. The general type is the most polypoid type, accounting for 90%, of which the broad base type is more common. Common base tissue infiltration in the base of the broad-based type. The type of early cancer is the most common type of tubular adenocarcinoma, especially moderately differentiated adenocarcinoma, and has a certain correlation with the general type. Early stage I and II cancers are more common in high and moderately differentiated adenocarcinomas, and type III is lower. Differentiated cancer is more common.
Biopsy specimens can not identify early cancer, and only the tumor lesions that have been surgically removed can be diagnosed by cutting and observing them.
2 Colon cancer tissue: There are two long-standing views on the organization of colon cancer: one type advocates that all colon cancers are transformed by adenoma malignant transformation, that is, adenoma-cancer-sequence Another type of colon cancer, in addition to adenoma, can also occur directly in the mucosa without adenoma, which originates from the flat mucosa (de novo), or the dysplasia-cancer sequence (dysplasia-carcinoma) Sequence). In recent years, studies on pathological specimens of colon cancer have shown that 39.8% are invasive or invasive type cancers, and only 0.5% of the colon cancers can be seen in residual adenoma tissues; and 25.8% in uplifted and localized ulcer types. Residual adenoma components can be found. The detection rate of the latter is related to the volume of the tumor, and the detection rate of adenoma in the tumor <2 cm is as high as 83%. Therefore, the author believes that there are two ways of colon cancer, invasive and invasive ulcer type colon cancer originated from the flat mucosa, while the uplift type and localized ulcer type mainly occurred on the basis of adenoma.
When discussing the problems of colon cancer tissue, the phenomenon of multi-center growth of colon cancer should also be mentioned. The multicentric growth of tumors is not unique to colon cancer, but the multicentricity of colon cancer is not uncommon. According to reports, the incidence of multiple primary cancers accounts for 1.5% to 2.5% of colon cancer. The Third Hospital of the Third Military Medical University reported that multiple primary cancers accounted for 10.53% of colon cancer in the same period. This phenomenon should be highly valued by cancer clinicians. Whether it is a medical, surgical or pathologist, in the preoperative, intraoperative and postoperative examination of colon cancer, attention should be paid to the presence of multiple primary cancers. In order to avoid missed diagnosis.
;
A.
B.
;
C.70Philipe(transitional mucosaTM);;(CEA);(McAb)MC3MC5CL-2CL-4DNADukes
3
Dukes1928Dukes2151Dukes
(1)Dukes(19321935)
A
B
CC1
C2
(2)KirklineDukes(1949)KirklineDukesAAB1B2 3C1C2C
A
BB1
B2
C
(3)AstlerDukes(1954)
A
B1
B2
C1
C2
AstlerDukesKirklineKirklineAstlerAstlerDukes
(4)AlanDukes(1978)AlanDukesWood1001530%40%56%100%
A1
A2
B2
B2
C1
C2
D
(5)AJC(1979)1959(UICC)TNM1959(AJC)TNMT1982Beahrs
TNM
T
Tx
To
Tis
T1
T2
Ta
Tb
T3
T4
T
N
Nx
No
N113
N2
N3
M
Mx
Mo
ML
AJC
0Tis N0 M0
AT1 N0 M0
BT2 N0 M0
T2 Nx M0
T3 N0 M0
any T N13 M0
T4 anyN M0
any T anyN ML
(6)(1978)1978DukesDukes
0 ()
1()
2
1()
2
1()
2()
()
3
4
Prevention
35
(initiation)(promotion)(progression)31035
1, primary prevention
(1)
Burkitt(AEC)
20BurkittpH
Howe5287104701312;C
(end-point)-() (intermediate markers)
(HTdR)(LI)LI(Br-UdR)(PCNA)C(PKC)(ODC)
Alberts 11713.5g/dLILI86LI22%(P<0 001="" reddy="" 10g="" d="" decosse="" 58="" fap="" 1="" 4="">11g/d)C(4g/d)E(400mg/d)
Schatzkin20792142AlbertArizona11429(2.0g/d)(13.5g/d)2FuchsGiovannucci111976121700()198088757(3459)19961678727530101220%0.95(95%CI0.731.25)
Cochrane200110(systemic review)meta5434924(RR)1.04(95%CI0.951.13)(RD)0.01(95%CI0.020.04)24
(2)(chemoprevention)
1(chemopreventive agentCPA)
Vogelstein(13)
(nonsteroidal antinflammatory drugs,NSAIDs)-1-2(COX-1COX-2)Thun1991662424198219890.770.730.600.5814790020.6830.35Giovannucci894460.62200.56
122071
NSAID110421765(Medicaid)NSAID0.61
()(RR=0.78RR=0.91)(RR=0.63RR=0.66)Giovannucci400µg(RR=0.25)15
Baron930(3g/d1.2g)214(RR=0.85)1
20-1(insulin growth factor-1)
Calle(RR=0.71)11(RR=0.54)(RR=0.65)52meta20%
ABDE
864CECE144
(3)
CrohnMorson54%1014%Stryker2024% Gilbertsen50451()251815813758085%1976Lee2523%5055%7030.7%
197719803015cm238 826407614101998660cm(1988)199219961977198141%29%
NCISloan- Kettering71(National Polyp StudyNlPS)NPS1980199091122632141825.95()290%88%76%
2
,
1015NCI(SEER)1978198359537594.1%(Dukes'A)84.6%5.7%
1385DukesABCD593.9%74.0%48.3%0.31%A+B40%C+D60%ArmitageDukes'A6%1973199520.5%7.4%1986
NCI(United States Preventive Service Task ForceUSPSTF)(American Gastroenterological Association)
(1)
8cm30%10%(1518cm)1.7%0.17%1197119864512(OR=0.96)
(2)
1967GreegorFOBTFOBT
Hemoccult (Smith Kline Diagnostics)H2O2;2mlHemoccult 46ml/100gFOBTRansohoffLangFOBTFOBT40%96%98%50%60%90%LiebermanFOBT50%(95%CI30%70%)()24% (95%CI19%29%)94%(95%CI93%95%)50FOBT2%FOBT10%30%FOBT()12.10% (23706/206125)
FOBT19751985Sloan-Kettering217564065%Dukes'AB33%;10(P<0.001)1043%(P=0.053)FOBT3(6)USPSTFA()
(3)
FOBT701987(RPHA-FOBT)13034RPHA FOBT11465(195)60cmRPHA-FOBT63.6%81.9%Youden0.46RPHA-FOBT22.1%40%7581330RPHA-FOBT4.2%21Dukes'AB71.4%
FOBT HemeselectInSureFlexsureOBT1InSure TM1240InSureTM87%(20/23)>10mm47.4%(9/19)14097.9%(88/98)3097.8%(92/94)InSureTMFOBT(ACS)FOBTFOBT2003ACS
(4)
Gilbertsen5018158(25cm)251969197660cm25cm60cm80%60cm
Kaisei(Kaiser Permanence Multiphasic Health CheckupMHC)355410713515620Dukes'A60%16590%1080%;Dukes'A48%1048%(1229)
Lieberman70%80%180%60cm65;1cm;
314782%60cm60cm316260cm21331;1303460cm1156360cm95%600060cm1
2SelbyNewcomb2170%90%
Thiis-Evensen198379981%13(1996)2451(71%)(1cm)(RR=0.695%CI0.31.0P=0.07)210(RR=0.295%CI0.030.95)()2ACSUSPSTF60cm
(5)
FOBT LiebermanImperiale(1cm)(0.3%1/20000)
(6)
ACS51(DCBE)DCBEWinawerDCBE<0 5cm="" dcbe="" 32="" 0="" 6="" 1cm="" 53="">1cm(2)48%DCBE85%DCBE
(7)
(ACS Colorectal Cancer Advisory Group)20024CT
CT(CT Colonography)(virtual colonoscopy)1994CT>1cmCT90%<0.5cm50%100%
DNAPCRDNAEXACTDNAK- rasAPCp5315bat-261612211128DNA91%82%93%K-ras73%100%
CTDNA(capsule video endoscopy)
(8)
1980(ACS)(American Gastroenterological Association)
ACS
A.ADAD0.3;RPHA FOBT2
B.60cm
C.60cmFOBTFOBT()
3075 813429960cm3162(73.6%)2162%Dukes A+B71.4%
A.40
B.160cmRPHA FOBT;;;2
C.60cmFOBT
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D.60cm
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3
Complication
Complications anemia
Symptom
3069
1, symptoms
(1)
;
(2)
(3)
(4)
(5)
3
312
2, signs
;
8cm
Examine
1(FOBT)
1967GreegorFOBTFOBT(SRID)(LA)(CIE)(ELISA)(RPHA)RPHARPHA63.6%72.7%RPHA81.9%61.7%RPHA
(dot-ELISA)
2
3
(1)
(2)
(3)
4(CEA)
1965Goldr26CEACEA(49%60%)(52%77%)(30%50%)(64%)(60%)CEACEA20CEACEACEACEA2
CEACEACEA50%CEA25%CEA>5µg/L(0.43)5µg/L
CEA6141013CEACEA2Moertal(1993)417CEA59%60016ACEA115CEA47(40.1%)Martin60CEA93.3%95%CEA17%25% CEACEA2
5
(PCR)-(PCR-RFLP)DNA101DNA2
(1)Ki-rasrasras351211(31.4%)61l(2.9%)11213GlyAsD(4)
(2)Ki-rasDNAKi-ras1PCRRFLP12186Ki-ras(33.3%)4Volgelstein249ras8
6
30cm226X
7
6%11%10%20%33%50%
(1)
96%ThoeriMenuk11.7%45.2%;87%59%96%X8.4%
70%80%(654-2)
(4);;40
(2)CT
CTCTCTCTMossCT
1(5mm)
2
3;
4()
CTCTCT48%72%25%73%
(3)MRI
MRICTMRI3
(4)
2
;;
5376%88.8%38%BCT
(5)
CEAAFPCA-50CA19-9
67Ga-25cm(74165mEq)2496h(ECT)67Ga131ICEA
Diagnosis
diagnosis
1();
2;
3;
4;
5
Differential diagnosis
1
X
2()
X10
3
X;X
