Introduction:
Colon cancerIt is a common digestive tract malignant tumor, accounting for the second place in the gastrointestinal tumor. The predilection site is the rectum and the junction of the rectum and the sigmoid colon, accounting for 60%. The incidence is more than 40 years old, the ratio of male to female is 2:1.
Cause:
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 someone's first-degree relatives, such as parents, have to endRectal cancerHe is eight times more likely to suffer from this disease in his lifetime than the general population. About a quarter of new-onset people have a family history of colorectal cancer.
3. History of colon disease: Certain colon diseases such as Crohn's disease or ulcerative colitis may increase the chance of developing colorectal cancer. Their risk of colon cancer is 30 times that of ordinary people.
4. Polyps: Most colorectal cancers develop from small precancerous lesions, which are called polyps. Among them, villus-like adenomatous polyps are more likely to develop into cancer, and the chance of cacao becomes about 25%; the malignant rate of tubular adenomatous polyps is 1-5%.
5. Gene characteristics: Some familial tumor syndromes, such as hereditary nonpolyposis colon cancer, can significantly increase the incidence of colorectal cancer. And the onset time is younger.
(1) Causes of the disease
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.
1. Epidemiological studies on dietary factors show that 70% to 90% of cancers are related to environmental factors and lifestyles, and 40% to 60% of environmental factors are related to diet and nutrition to some extent. Dietary factors in the onset of cancer are considered to be extremely important factors.
(1) Mechanism of action of high fat, high protein and low cellulose: can be summarized as follows:
1 affects intestinal lipid metabolism, high-fat diet increases 7a-dehydroxylation enzyme activity, leading to increased formation of secondary bile acids, while cellulose has the opposite effect, and inhibits reabsorption, dilution and adsorption, chelation Lowering the deoxycholic acid concentration in the intestine increases the solid phase material in the feces and promotes excretion; some dietary factors (such as calcium ions) can lower the levels of intestinal ionized fatty acids and free bile acids, both of which are on the intestinal epithelium It has a damaging effect; it inhibits 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. Injury of the epithelium;
3 high fat and some carbohydrates can increase intestinal enzyme activity (such as glucuronidase, ornithine dehydrogenase, nitroreductase, azooxygenase, lipoxygenase, cyclooxygenase) to promote carcinogenesis The production of substances 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 studies have shown that carotene, vitamin B2, vitamin C, and vitamin E are all associated with a reduction in the relative risk of colon cancer, and are dose-response. Vitamin D and calcium have a protective effect.
(3) Onion and garlic: The protective effect of onion and garlic on the body has been widely recognized, and the inhibition of tumor growth on this type of food has been confirmed many times in the experiment. 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 food: 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, and the case-control study suggested weekly intake. The excess risk of colon cancer in three or more preserved 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 are a strong antioxidant that inhibits the carcinogenic effects 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.
2. Occupational factors and physical activity 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.
3. Genetic factors It is estimated that genetic factors may play an important role in at least 20% to 30% of colon cancer patients, 1% of which are familial polyposis and 5% of hereditary polypoid-free colon cancer syndrome patient. 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.
4. Disease factors
(1) Intestinal inflammation and polyps: chronic intestinal inflammation and polyps, adenomas and patients with extensive ulcerative colitis for more than 10 years: the risk of developing colon cancer is several times higher than that of 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. Relevance. 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 more than 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.
(two) pathogenesis
1. The pathogenesis is based on modern biology and epidemiology 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. Gradually developed into cancer, due to 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 G→C 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 (GC→AT).
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. The new gene, DCC gene, is a large gene, over 70kD. Its function has not yet been completely determined. The inactivation of DCC gene in colon cancer is likely to cause extracellular information molecules from other cells, extracellular matrix or soluble molecules. The recognition changes 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, 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 β (TGF-α, TGF-β), 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 α and β 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/β-caterin and TGF-β 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 some 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.
3 Diagnostic criteria for adenoma carcinogenesis: The standard of adenoma carcinogenesis is quite different at home and abroad. The general trend is that European and American scholars have stricter criteria for diagnosing cancer, and often emphasize that they can be identified as cancer when infiltrated; Japanese scholars often treat severe abnormalities. The diagnosis of hyperplasia is cancer. Domestic scholars have made recommendations on the criteria for adenoma carcinogenesis. After the study of the National Colon Cancer Pathology Cooperative Group, they agreed to adopt it.
4 diagnostic criteria for carcinoma in situ:
A. Some of the glandular or villus epithelial cells are low-column or polygonal and have obvious heteromorphism. The nucleus is significantly enlarged and rounded, the polarity disappears, the nucleolus is large and obvious, the mitotic figures are more common, and pathological mitosis occurs.
B. Submucosal invasive carcinoma: The cancerous tissue penetrates the mucosal muscle layer and invades the submucosal tissue, but does not affect the muscularis propria. Once the tumor tissue invades the muscularis propria, it is advanced colon cancer.
In practice, the diagnostic criteria for cancer is often difficult to achieve complete uniformity, but the principle of adenoma and early cancer treatment is the same, that is, intramucosal cancer or submucosal cancer only invades the top or stem of polypoid adenoma. For adenoma pedicle root resection; if the cancer tissue has infiltrated into the tumor pedicle root, it should usually be considered for radical resection. Therefore, regardless of whether the surgeon or pathologist treats such adenomas, he must pay great attention to the violation of the bottom and lateral margin of the adenoma stem.
C. Colon cancer adjacent to the transitional mucosa: Since the famous British pathologist Philipe in the 1970s, there is a transitional mucosa (TM) next to colon cancer, and it is believed that the mucosa is a concept of precancerous lesions of colon cancer. The extensive attention has been paid to the field of tumor pathology, but there are still different views on the nature of whether the transitional mucosa is a precancerous lesion.
In recent years, many scholars have studied the characteristics and nature of migration mucosa from various angles such as morphology, ultrastructure, quantitative detection, mucus histochemistry and immunohistochemistry. It is found that the migration mucosa does indeed differ in morphology and function. The normal mucosa is different: the gland is dilated, prolonged, twisted or branched in the transitional mucosa, and the glandular epithelial cells are enlarged; the intracellular sialic acid mucin content is increased, the sulfated mucin is reduced or disappeared; the carcinoembryonic antigen The detection rate of (CEA) was higher than that of normal mucosa and could occur in the cytoplasm; with the monoclonal antibodies (McAb) MC3, MC5, CL-2, CL-4, etc. of colon cancer, the positive rate of transitional mucosa was significant. Higher than normal mucosa. In addition, the DNA content in the nucleus of transitional mucosal epithelial cells is similar to that of cancer cells, and the number of cells in triploid, tetraploid and even tetraploid is significantly increased, similar to the ploidy type of cancer cells.
Domestic Guo et al. further analyzed the relationship between the distribution of transitional mucosa and the prognosis of colon cancer. It was found that the wider the distribution of migration mucosa, the worse the histological differentiation of the tumor, and the later the Dukes stage of the patient. According to the above characteristics of the transitional mucosa, most scholars believe that the transitional mucosa is a mucosa with abnormal differentiation of cells. This change is caused by inflammation, and may also be dysplasia manifested by tumor formation. Therefore, patients with transitional mucosa found in biopsy specimens should be followed up to detect early colon cancer.
3. The prognosis of clinical pathological stage of intestinal cancer Although affected by many factors, the most significant is the depth of invasion of the intestinal wall and the presence or absence of metastasis in the peri-intestinal lymph nodes and distant. As Dukes proposed in 1928, "the survival of colon cancer and the infiltration of lesions in the intestinal wall and subsequent involvement of lymph nodes are closely related." Subsequently, Dukes first analyzed 215 cases of rectal cancer based on these two indicators, and proposed a meaningful clinical pathological staging program, which was endorsed by most scholars. In the specific application, it has been revised and revised, which is called the improved Dukes staging plan.
(1) Dukes staging (1932 ~ 1935):
Stage A: The tumor is limited to the intestinal wall.
Stage B: The tumor invades the peri-intestinal tissue, but no lymph node metastasis.
Stage C: C1: Tumor invades the peri-intestinal tissue, with lymph node metastasis below the vascular ligation.
C2: The tumor invades the peri-intestinal tissue, and there is a lymph node metastasis above the vascular ligation.
(2) Kirkline modified Dukes staging (1949): Kirkline further divided DukesA into stage A, B1 and B2, and proposed the carcinoma in situ, the significance of prominent muscle layer in tumor spread, combined with C1 and C2 as C phase. However, cases of peri-intestinal tissue infiltration and distant metastasis were not included.
Stage A: The tumor only invades the mucosa.
Stage B: B1: The tumor infiltrates the muscle layer but does not penetrate.
B2: The tumor has penetrated the muscle layer.
Stage C: The tumor invades part of the intestinal wall or the entire intestinal wall with lymph node metastasis.
(3) Astler improved Dukes staging (1954):
Stage A: The tumor only affects the mucosa.
Stage B1: The tumor infiltrates the muscle layer but does not penetrate.
Stage B2: The tumor has penetrated the muscle layer.
Stage C1: The tumor is confined to the intestinal wall with lymph node metastasis.
Stage C2: The tumor has penetrated the intestinal wall with lymph node metastasis.
Astler's improved Dukes staging compared with the Kirkline program, in addition to the advantages of Kirkline staging, highlights the significance of serosal infiltration. However, the Astler protocol did not include cases where the cancer had penetrated the intestinal wall without lymph node metastasis and distant metastasis. Astler's improved Dukes staging has been adopted by most US literature.
(4) Alan modified Dukes staging (1978): Alan improved Dukes staging based on Wood's prognostic indicators, based on his own 100 cases of colon cancer case analysis, proposed a simple and easy to understand, easy to apply improved program. The 5-year survival rate of lymph node metastasis was 30% to 40%, and the lymph node metastasis was 56% to 100%. However, this program did not estimate the cases of invasion of adjacent organs.
A1: Above the submucosa, lymph node metastasis (-).
A2: Above the submucosa, lymph node metastasis ( ).
B2: Muscle layer, lymph node metastasis (-).
B2: Muscle layer, lymph node metastasis ( ).
C1: full layer of intestinal wall, lymph node metastasis (-).
C2: full layer of intestinal wall, lymph node metastasis ( ).
D: Remote transfer.
(5) AJC staging (1979): Since the International Anti-Cancer Alliance (UICC) proposed the clinical staging system of TNM tumors in 1959, the cancers of the main organs of the human body have listed the specific staging plan according to the staging principle. The lesion is difficult to estimate and has not been adopted as an exception. The 1959 American Cancer Staging and Results Reporting Association (AJC) conducted an in-depth study of the principle of TNM staging applied to colon cancer, but the content was different from other tumors. "T" refers to the infiltration of tumors in the intestinal wall and intestine, unlike other tumors as markers of tumor size. The specific solutions provided by Beahrs in 1982 are as follows:
1TNM standard:
T: range of direct infiltration of primary cancer.
Tx: The depth of the intestinal wall infiltrated by the cancer is not certain.
To: No tumor was found in the clinic.
Tis: histological examination is carcinoma in situ.
T1: Cancer is confined to the mucosa or submucosa.
T2: Cancer infiltration is limited to the intestinal wall but not penetrated.
Ta: Part of the intrinsic muscular layer infiltration.
Tb: all intrinsic muscular layer infiltration.
T3: The cancer infiltrates the entire layer of the intestinal wall with or without invasion of adjacent tissues or organs, with or without fistula.
T4: The extent of direct spread of cancer has exceeded that of adjacent tissues and organs.
( ) T: multiple primary cancers, of which the largest tumor is described by the above provisions, and the number of tumors is filled in brackets.
N: Lymph node metastasis.
Nx: Unable to estimate.
No: I don't think there is lymph node metastasis.
N1: 1 to 3 local lymph node metastases ( ) adjacent to the primary lesion.
N2: lymph node metastasis outside the margin of the mesentery or outside the vascular ligation line ( ).
N3: The location of the metastatic lymph nodes is inaccurate, the number of lymph node examinations ( ), and the number of metastatic lymph nodes ( ).
M: Remote transfer situation.
Mx: Unable to estimate the remote transfer situation.
Mo: The distant transfer is not clear.
ML: There is a distant transfer, transfer site _________.
2AJC colon cancer staging program:
Stage 0: Tis N0 M0 histological examination for carcinoma in situ.
Stage IA: T1 N0 M0 cancer is limited to mucosa or submucosa, no lymph nodes and distant metastasis.
Stage IB: T2 N0 M0 Cancer is limited to the intestinal wall.
T2 Nx M0
Stage II: T3 N0 M0 The cancer infiltrates the whole layer of the intestinal wall and its adjacent structure, with no lymph nodes and distant metastasis.
Stage III: any T N1 ~ 3 M0 cancer invades any level of the intestinal wall with regional lymph node metastasis.
T4 anyN M0 cancer infiltrates hyperadjacent tissue or infiltrates adjacent organs without local lymph node metastasis.
Stage IV: any T anyN ML cancer invades any level of the intestinal wall, with or without lymph node metastasis, has been far
Transfer.
(6) National Colon Cancer Collaborative Conference (1978, Hangzhou): Chinese scholars in the 1978 provincial and municipal colon cancer collaboration group meeting held in Hangzhou, a comparative analysis of various Dukes staging improvement programs, proposed China's Dukes staging improvement program.
Stage I: 0 The lesion is limited to the mucosa (including carcinoma in situ) for local excision.
1 The lesion invades the submucosa (early invasive carcinoma).
2 The lesion invades the muscle layer.
Stage II: The lesion invades the serosa or invades the tissues and organs of the intestine, and can be removed or removed in a single piece.
Stage III: 1 lymph node metastasis (intestinal or para-intestinal lymph nodes) near the lesion.
2 The lymph node metastasis around the perivascular and mesangial margin can be used for radical resection.
Stage IV: 1 with distant organ metastasis (liver, lung, bone, brain).
2 with extensive lymph node metastasis (left supraclavicular), or a wide range of lymph nodes supplying the root of the blood vessel.
Metastasis, can not be completely removed (anterior or para-aortic and iliac lymph nodes, etc.).
3 With the extensive spread of the peritoneum, it is impossible to remove all of them.
4 The lesion has been extensively infiltrated into adjacent organs and cannot be removed.
symptom:
History and symptoms:
Most of the changes in bowel habits or fecal traits are due to increased stool frequency, no shape or loose stools, and blood and mucus in the stool. Sometimes constipation or diarrhea alternates with constipation, and the stool becomes thinner. Pain in the lower abdomen, the degree is different, mostly pain or pain. Abdominal masses are often found in patients with right colon cancer. Note that patients with or without blood, weight loss, fatigue, edema, hypoproteinemia and other systemic symptoms, tumor necrosis or secondary infection, patients often have fever.
Physical examination found:
It can be found in the abdomen mass or the intestines. The mass of the mass is accompanied by tenderness and irregular shape. Anemia, weight loss, cachexia. Compression of venous return with lymphatic metastasis can cause ascites, lower extremity edema, jaundice and so on.
Colon cancer is more common in middle-aged and elderly people, with the majority of 30-69 years old, more men than women. Early symptoms are not obvious. Common symptoms in patients with advanced disease include abdominal pain and gastrointestinal irritation, abdominal mass, bowel habits and fecal trait changes, symptoms caused by anemia and chronic toxin absorption, intestinal obstruction, and intestinal perforation.
Symptom
(1) abdominal pain and digestive tract irritation symptoms: Most patients have varying degrees of abdominal pain and abdominal discomfort, such as abdominal pain, right abdominal fullness, nausea, vomiting and loss of appetite. Symptoms often worsen after eating, sometimes accompanied by intermittent diarrhea or constipation, easily associated with chronic appendicitis common in the lower right abdomen, ileocecal tuberculosis, ileocecal segmental enteritis or lymphoma. Colonic hepatic squamous cell carcinoma can be characterized by paroxysmal cramps in the right upper quadrant, similar to chronic cholecystitis. It is generally believed that the pain of the right colon cancer is often reflected to the upper part of the umbilicus; the pain of the left colon cancer is often reflected to the lower part of the umbilicus. If the cancerous tumor penetrates the intestinal wall to cause local inflammatory adhesions, or forms a local abscess after chronic perforation, the pain site is the site where the cancer is located.
(2) Abdominal mass: generally irregular shape, hard texture, nodular surface. There is a certain degree of mobility and tender tenderness in the early stage of transverse colon and sigmoid colon cancer. If the ascending or descending colon cancer has penetrated the intestinal wall and adheres to the surrounding organs, the chronic perforation forms an abscess or pierces the adjacent organs to form the internal hemorrhoids, the mass is more fixed, the edge is unclear, and the tenderness is obvious.
(3) Defecation habits and fecal trait changes: the result of ulceration and secondary infection for cancer necrosis. As the toxin stimulates the bowel to change the bowel habits, the number of bowel movements increases or decreases, sometimes diarrhea and constipation alternate, there may be abdominal cramps before defecation, and then relieved. If the location of the cancer is low or located in the rectum, there may be rectal irritation such as anal pain, poor bowel movements or urgency. Feces often do not form, mixed with mucus, pus and blood, sometimes blood is often misdiagnosed as dysentery, enteritis, hemorrhoids and so on.
(4) Anemia and chronic toxin absorption symptoms: The surface necrosis of the cancer can form a persistent small amount of oozing, and the mixing of blood and feces is not easy to attract the attention of the patient. However, anemia, weight loss, weakness, and weight loss can occur due to chronic blood loss, toxin absorption, and malnutrition. Late patients have edema, hepatomegaly, ascites, hypoproteinemia, cachexia and other phenomena. If the cancer penetrates the stomach and the bladder forms internal hemorrhoids, the corresponding symptoms may also appear.
(5) Intestinal obstruction and intestinal perforation: due to intestinal blockage, intestinal tube itself narrowing or adhesion outside the intestinal cavity, compression. Most manifested as incomplete intestinal obstruction with slow progression. Early patients with obstruction may have chronic abdominal pain with bloating and constipation, but they can still eat and have severe symptoms after eating. Symptoms can be alleviated after treatment with laxatives, colon cleansing, and traditional Chinese medicine. After a long period of recurrent episodes, the obstruction gradually becomes complete. Some patients appear in the form of acute intestinal obstruction, and more than half of the acute colonic obstruction in the elderly is caused by colon cancer. When the colon is completely obstructed, the ileocecal valve blocks the colon contents from flowing back to the ileum to form a closed intestinal obstruction. The colon from the cecum to the obstruction can be extremely inflated, the intra-intestinal pressure is constantly increasing, and rapidly develops into strangulated intestinal obstruction, and even intestinal necrosis, causing secondary peritonitis. Some patients have atypical symptoms and are difficult to preoperative. Clear diagnosis. Cancers located in the cecum, transverse colon, and sigmoid colon can cause intussusception when the peristalsis is severe.
Colon cancer patients do not necessarily have the above-mentioned typical symptoms, and their clinical manifestations are related to the location of the cancer, the type of pathology, and the length of the disease. The colon can be divided into left and right halves by the spleen of the colon. The two halves are different from embryonic origin, blood supply, anatomical and physiological functions, intestinal contents and common cancer types. There are significant differences in diagnostic methods, surgical methods, and prognosis.
The right colon colon originates from the midgut and the intestine is large, and the contents of the intestine are liquid. One of the main functions is to absorb water. The cancer is mostly mass or ulcer type. The surface is easily bleeding, and the toxin produced by the secondary infection is easily absorb. The three main symptoms are the symptoms of right anterior abdominal and digestive tract irritation, abdominal mass, anemia, and chronic toxin absorption, and less chance of intestinal obstruction.
The left colon embryo originates from the hindgut, the intestinal lumen is fine, and the contents of the intestine are solid. The main function is to store and discharge the feces. The cancer is mostly infiltrated and easy to cause the intestinal lumen to be narrowed. The three main symptoms are common bowel habits, bloody stools and intestinal obstruction. Intestinal obstruction can be manifested as a sudden onset of acute complete obstruction, but most of them are chronic incomplete obstruction, abdominal distension is obvious, the stool becomes thin like a pencil, and the progressive progression of symptoms eventually develops into complete obstruction. Of course, this distinction is not absolute, and sometimes there are only one or two clinical manifestations.
2. Physical examination of physical signs may vary depending on the course of the disease. Early patients may have no positive signs; those with longer course of disease may have a bump in the abdomen, and may also have signs of weight loss, anemia, and intestinal obstruction. If the patient has intermittent "a gas-like" mass in the abdomen, accompanied by colic and bowel sounds, the possibility of colon intussusception caused by colon cancer should be considered. If the left supraclavicular lymphadenopathy, hepatomegaly, ascites, jaundice or pelvic mass are found to be late manifestations. There are tenderness in the liver, lung and bone metastases.
diagnosis:
Rectal examination is a non-negligible examination method. It is generally known that there are polyps, lumps, and ulcers within 8 cm from the anus. Low sigmoid colon cancer can be accessed through abdominal and rectal double diagnosis. At the same time, attention should be paid to the presence or absence of metastatic mass in the pelvic cavity. Female patients can be diagnosed in the abdomen, rectum, and vagina.
The basic premise of colon cancer treatment is to have a comprehensive and correct tumor diagnosis. The diagnosis of tumor is based on the comprehensive medical history, physical examination, and related equipment examination. The general preoperative diagnosis mainly includes the tumor condition and other conditions of the whole body.
1. Tumor condition
(1) Location diagnosis of tumors: that is, to identify the site where the tumor exists, to understand the relationship between the tumor and adjacent tissues and organs, and whether there is distant metastasis.
1 Anatomical part of the tumor: clinically, the anatomical part of the tumor should be clearly defined. We can determine it by the following various positioning diagnostic techniques: A. Physical examination of the lumps is a simple and effective method, but pay attention to the partial freeness. Large transverse colon and sigmoid colon tumors may not be in a conventional position, causing misjudgment. BB super, CT, MRI can determine the presence or absence of the mass and the location of the mass, but sometimes the tumor is small, the above examination can not be judged. C. Fiber colonoscopy In addition to the rectum, the positioning function of other parts is unreliable, mainly due to the non-linear relationship between the colonoscope and the intestine, the intestine can be elongated or nested, often in clinical practice. It can be seen that there is a huge difference between colonoscopy and surgery, which makes surgery difficult. D. The best localization diagnosis method for colon tumor is barium enema examination, which can give us the most intuitive and accurate tumor site, and also give us the length and tightness of the intestine, help us to determine the surgical incision selection and resection of the intestine. range.
2 The relationship between tumor and surrounding tissue structure: In addition to clarifying the anatomy of the tumor, it is very important to understand the relationship between the tumor and surrounding tissues and organs, especially the relationship with important organs and large blood vessels. The relationship between the general colon and surrounding tissues is not Too close, only when the tumor is large, it can invade other organs. The main ones have large ileocecal tumors that invade the iliac vessels and ureters; the colonic liver cancer invades the duodenum and the head of the pancreas; and the colon cancer invades the ureter. Knowing the relationship between the tumor and the surrounding tissue before surgery has certain value for the judgment of preoperative resection and the notification of the patient and family.
3 distant metastasis of the tumor: for malignant tumors, in addition to the situation of the primary tumor is very important, the situation of metastases is more important, because with the metastases, the entire treatment plan will undergo major changes, so carefully before surgery Check for possible metastases is a routine preoperative examination. For colon cancer, pelvic floor metastasis, retroperitoneal lymph nodes, liver, and lung are common sites of metastasis and should be routinely examined. For rare bones, brains, and adrenal glands, it is determined according to clinical symptoms whether or not to perform brain CT and bone scan.
(2) Qualitative diagnosis of tumors: The qualitative diagnosis of diseases requires the following questions: 1 whether the disease is a tumor; 2 is a malignant tumor or a benign tumor; 3 is which type of malignant tumor, which type. The first two determine the scope of surgery and surgery; the latter will determine the way the surgery is performed.
Although physical examination, B-ultrasound, CT, MRI, endoscopy can be a preliminary qualitative diagnosis, the qualitative diagnosis of colon cancer depends on histopathological diagnosis.
It should be noted that malignant tumors that can be diagnosed clinically are sometimes not necessarily malignant. Some authors have reported cases of preoperative pathological examination of colorectal cancer repeated 8 times (including fiberoptic colonoscopy, sigmoidoscopy, and anal biopsy). This is related to the size of the tissue biopsy site and the size of the tissue block. Therefore, when clinically suspected malignant tumors must be repeatedly checked, do not arbitrarily give up the examination, delaying the diagnosis and treatment of the disease. In the clinical treatment of colon cancer, there are several requirements for preoperative pathology: for colon cancer and colon cancer that can certainly retain the anus, the current pathology can be uncertain, but there must be a clear lesion and reach a certain level. The size of the rectal cancer, which cannot clearly preserve the anus, must have a pathological diagnosis before surgery.
(3) Quantitative diagnosis of tumors: Quantitative diagnosis of tumors can be broadly divided into two aspects: 1 the size of the tumor. There are two representations: the maximum vertical diameter representation of the tumor and the representation of the tumor invading the circumference of the intestine. The former is mostly used for larger tumors. Generally, the maximum diameter of the tumor is multiplied by its maximum vertical diameter, expressed in centimeters. The latter is mostly used for small and small tumors, which are still limited to the extent of the intestine. The clinical use of tumors accounts for the extent of the intestinal canal. To indicate, for example, 1/2 circle; 2 the volume or weight of the tumor, the volume and weight of the tumor are less applied to intestinal cancer, and the method is mostly used for larger solid tumors, such as soft tissue tumors.
(4) Preoperative staging of tumor: The preoperative staging of colon cancer is the same as other tumors, and there is a problem of accuracy of staging. Generally, according to the above tumor location, qualitative and quantitative, a preoperative staging can be given. This staging is often quite different from postoperative staging. Current research has shown that clinical guidance for colon cancer preoperative staging is of little significance, but preoperative staging is significant for WHO stage II or III, which has invaded the intestinal wall or has metastatic lymph nodes in the middle and lower rectal cancer. Can guide neoadjuvant radiotherapy and chemotherapy.
2. Diagnosis and treatment of systemic non-neoplastic diseases In the treatment of tumor diseases, the understanding and treatment of the health status of other tissues and organs throughout the body is also an important basis for the development of treatment plans.
(1) Examination of the state of the body: The tumor is a disease that increases with age, and most patients are older than 50 years old. Most of them have some chronic diseases, such as cardiovascular and cerebrovascular diseases, respiratory diseases, liver and kidney system diseases, and diabetes. Shi Yingqiang reported that a group of elderly colon cancer patients, 66% have various types of chronic diseases. The authors emphasize that a comprehensive physical examination should be performed on any patient with cancer, including: conventional electrocardiogram, chest X-ray, liver and kidney function, blood routine, coagulation function, infectious disease, and diabetes-related tests. For symptomatic or check-up situations, further examinations such as echocardiography, cardiac function, lung function, EEG, and bone marrow function should be performed.
(2) Examination of diabetes: Diabetes is closely related to colon cancer. In the general population over 60 years old, the incidence of diabetes is 42.7%. Because diabetes has the same pathogenic factors as colon cancer, such as high protein, high fat, high calorie, low cellulose, and less exercise, the incidence of diabetes in colon cancer patients is significantly higher than that in the general population. Mo Shanzhen's study of colon cancer and gastric cancer admitted in 1993-1994 showed that the detection rate of diabetes in colon cancer was 17.6%, while the detection rate of diabetes in gastric cancer was only 6.3% (P<0.025), which was significantly higher than normal. crowd. Due to the disorder of glucose metabolism in diabetes itself and the stress response under the operating state, the healing of the anastomosis of the operation can be delayed, the anti-infective ability can be reduced, and the postoperative complications can be increased. Therefore, it is very important to detect diabetic patients before surgery. Most hospitals use diabetes history and fasting blood glucose to check for diabetes, but Mo Shanzhen research suggests that only 14.3% of patients can be detected by diabetes history; 37.1% of patients can be detected by fasting blood glucose; glucose tolerance test is the most reliable For the detection method, it is best to perform a routine glucose tolerance test before the anastomosis operation. In the glucose tolerance test, some patients have the following 1 or 2 abnormalities, although they can not be diagnosed as diabetes, but also suggest that the patient has abnormal glucose metabolism. In the case of surgical stress, it is also necessary to pay attention to the detection or application of insulin to control blood sugar.
1WHO Diabetes Diagnostic Criteria (1998): A. Diabetes Mellitus Symptoms Symptoms + Random Blood Glucose ≥11.1mmol/L; or B. Fasting Blood Glucose ≥7.0mmol/L; or C.OGTT 2h Postprandial Blood Glucose ≥11.1mmol/L.
2 fasting blood glucose ≥ 6.1 ~ <7.0mmol / L, or 2h postprandial blood glucose ≥ 7.8 to <11.0mmol / L for impaired glucose tolerance.
3 The symptoms are not typical and need to be confirmed again on another day. For asymptomatic patients, there must be 2 abnormal blood glucose to diagnose.
Identification
The clinical identification points are the length of the disease, the detection of parasites in the feces, and the morphology and extent of the lesions seen in the barium enema. The most reliable of these is still a biopsy through a colonoscope.
1. Idiopathic ulcerative colitis accounts for 15% of misdiagnosed cases. Colon cancer, especially papillary carcinoma or cauliflower-like carcinoma of the left colon, when the disease progresses to a certain extent, symptoms such as diarrhea, mucus, pus and bloody stools, increased frequency of bowel movements, abdominal distension, abdominal pain, weight loss, anemia, etc. are often accompanied. Infected people may still have symptoms such as fever and other symptoms, which are similar to the symptoms of idiopathic ulcerative colitis. When X-ray is checked, there are similarities between the two. Therefore, it is easy to cause misdiagnosis in the clinic, especially for young patients, and the presence of tumors is less thought.
2. Appendicitis accounts for about 10% of misdiagnosed cases. The ileocecal cancer is often diagnosed as appendicitis due to local pain and tenderness. Especially in advanced ileocecal cancer, local necrosis and infection often occur, clinical manifestations of elevated body temperature, increased white blood cell count, local tenderness or touch of the mass, often diagnosed as appendix abscess, and conservative treatment. After a period of treatment, the tumor does not shrink or even enlarge, and the tumor is considered. In general, the appendix abscess has a serious history of the disease, and there is inflammation, which can be obviously improved after short-term treatment. Such as cancer and appendicitis coexist or due to cancer caused by appendix obstruction caused by appendicitis, although the treatment has improved, but will not be thorough, continue to increase after stopping the drug to be further examined and diagnosed. Surgical exploration should be performed promptly when highly suspected.
3. Intestinal tuberculosis Intestinal tuberculosis is more common in China, and its predilection site is at the end of the ileum, cecum and ascending colon. The most common clinical symptoms include abdominal pain, abdominal mass, diarrhea, and constipation, which are more common in colon cancer patients. In particular, proliferative intestinal tuberculosis has many similarities with colon cancer, such as low fever, anemia, weight loss, fatigue, and local swelling. However, the systemic symptoms of intestinal tuberculosis are more obvious, manifested as low fever or irregular fever in the afternoon, night sweats, weight loss and fatigue. Therefore, when these symptoms appear clinically, especially when diarrhea is the first diagnosis, it is often easy to consider from the perspective of common diseases and frequently-occurring diseases. About 1% of patients misdiagnosed colon cancer as intestinal tuberculosis before surgery. There was a special change in the blood picture, and the blood sedimentation was fast. The tuberculin test was strongly positive. A combination of medical history, age, and general performance can generally confirm the diagnosis.
Colonic polyps Colon polyps are common benign tumors, most of which occur in the sigmoid colon. The main symptoms are blood in the stool, blood is blood, not confused with feces, and some patients may have pus and bloody stools. X-ray examination showed a filling defect. If the pathological examination of the fiberoptic colonoscopy is not performed, the polypoid colon cancer can be misdiagnosed as colon polyps. Adenomas and polyps are the most common benign tumors and tumor-like lesions of the colon. There are significant differences in histology: adenomas can develop cancer, and polyps do not turn into cancer. Both can be single or multiple. In the X-ray gas double examination, the round or oval filling defect is smooth and sharp. In the intestinal lumen, if the pedicle can move up and down, the contour of the colon is not changed, and there is a small amount in the vicinity of the adenoma or polyp. The tincture forms a circular shadow that contrasts sharply with the gas. Fibrous colonoscopy and biopsy for pathological examination are the most effective methods of identification.
5. Schistosomiasis granuloma is more common in epidemic areas. It is more common in southern China. It is rare to see the prevention and control of schistosomiasis after liberation. Intestinal schistosomiasis is the deposition of schistosomiasis eggs under the intestinal mucosa, causing large chronic inflammatory granuloma in the early stage. In the late stage, the colonic fibrous tissue proliferates, and adheres to the surrounding tissues to form an inflammatory mass, and the colonic mucosa continuously forms ulcers and scars. Polypoid hyperplasia can be formed due to ulcer repair of tissue hyperplasia. A small number of cases can be cancerous, and colon cancer and intestinal schistosomiasis in the endemic areas account for 48.3% to 73.9%, indicating that schistosomiasis is closely related to colon cancer. Therefore, patients with intestinal schistosomiasis who have lived in epidemic areas or have lived in endemic areas have been diagnosed for the past and are more likely to be associated with colon cancer or cancer. In addition to X-ray and fiberoptic colonoscopy and biopsy, combined with the history of schistosomiasis infection, the examination of eggs in feces, all contribute to the identification of intestinal cancer caused by colon cancer and schistosomiasis.
6. Amoebic granuloma in the formation of amoebic granuloma according to the location of the colon, in the corresponding part of the abdomen can be lumps and lumps or intestinal obstruction. Amoebic trophozoites and cysts can be found during stool examination. X-ray examinations of 30% to 40% of patients may have positive findings, and polyps on the mucosa. Amoebic granulomas are multiple, often producing large unilateral marginal defects or circular incisions on the intestine.
complication:
When a tumor develops to a certain stage, especially when it has already caused obstruction, it will trigger a series of symptoms. These include: weakness, fatigue, anemia, unexplained weight loss, persistent abdominal pain, melena or bloody stools, changes in bowel habits, etc. Rectal cancer can locally invade the bladder, vaginal wall, or peripheral nerves, causing pain in the perineum or tibia, but these symptoms occur late. Anemia, colonic fistula, partial or complete intestinal obstruction and intestinal perforation are common complications of colon cancer and are also the main cause of patient visits.
treatment:
Western medicine treatment
The treatment of colon cancer is still based on the basis of surgery. Surgery is the preferred treatment for patients with surgical indications. The radical surgery is a large resection of the primary lesion.
Colon cancer is the same as other cancers. It is a systemic disease with local manifestations. The 5-year survival rate is still below 50%. Effective comprehensive treatment or appropriate adjuvant radiotherapy and chemotherapy are clinically important aspects, but It is still controversial and has not seen encouraging results. Among the treatment failures, local recurrence and metastasis are common, including liver and lymph nodes, lungs, and brain. Therefore, in addition to improving the diagnosis rate in the early or asymptomatic stage, the clinic should not only strive to improve the adjuvant treatment effect, but also the surgeon should carefully design the surgical treatment of each body case, and strive to improve the success rate of surgery. It should be planned from preoperative preparation, surgical design and postoperative treatment follow-up, as well as adjuvant treatment at each stage. From the local tumors in each case, with or without spread and scope, to develop an individualized overall treatment plan.
Surgical treatment
(1) Preoperative estimation:
1 Estimation of systemic conditions: including general physiological conditions, cardiopulmonary function and the presence or absence of chronic wasting diseases such as diabetes, hypertension, and past history and surgical history. Pay attention to the general medical history and physical examination as well as laboratory tests. If there is functional influence or hypoproteinemia or anemia, actively perform preoperative preparation and correct correction at the same time, and strive for limited operation.
2 Estimation of tumor spread: A. Abdominal examination with or without ascites, colon cancer with ascites often reflects intraperitoneal implantation. B. There are no nodules in the skin or subcutaneous of the abdominal wall, especially the umbilical nodules, and there are no enlarged lymph nodes on the underarms and clavicle. C. Liver size, with or without jaundice, with or without nodules and hardness when touching the liver. D. Abdominal palpation, sometimes touching the mass, in the blind, ascending, descending and sigmoid colon, pay attention to the size and hardness of the palpation of its activity, with or without adhesion, fixation. E. In the rectal examination, the rectal bladder fossa is explored, and occasionally the sigmoid colon and the upper rectal cancer mass can be touched through the rectal wall. However, it is difficult to exclude tumor fixation caused by secondary infection. E. Scanning technology detects the spread.
3 Synchronous tumor discovery: Colon cancer synchronous tumors are more common, generally accounting for 3% to 9%, of which 30% are adenomas, so there should be an estimate before surgery. If there is no obstruction, full-length endoscopy and/or gastroenterology of the colon before surgery should be classified as routine.
4 Estimation of preoperative staging: It is one of the current clinical concerns. Although there are various methods to help diagnosis, but there are still different views on its significance, ultrasound examination and CT examination are still listed as routine examination methods: CEA test helps to judge the prognosis, high level CEA indicates extensive metastasis (liver, bone, etc.) The existence of the possibility, it should be emphasized that the final staging can not be based solely on a certain project index, but should be based on the combination of surgery and pathology clinical pathological staging.
(2) Intestinal preparation: In the initial stage, in addition to eating liquid, the patient is starved for 4 to 5 days, often need to be hospitalized in advance, and gradually prepare for preoperative, including fasting slag-free ingredients, oral total enema, cleansing enema and Rectal cleaning, etc. The above methods or combined applications, or one of them, the main point is to adapt to different requirements.
1 diet adjustment: 2 days before surgery into the slag-free semi-liquid, the first day into the liquid diet, fast morning fast. If the hungry can get a small amount of syrup or chocolate candy, milk should be avoided.
2 application of laxatives:
A. Oral ionic laxative method: The prescription of ionic laxative is: sodium chloride 3.07g, potassium chloride 0.38g, sodium bicarbonate 0.47g, the above dosage is 1 package, a total of 6 packs. Each pack is brewed with 500ml of warm water. Oral 1 day before surgery. Take 1 pack every 20 to 30 minutes. The diarrhea can be produced 1 hour after the service, and the effluent can be water sample without feces. The preparation method is simple and economical, and the intestinal cleanliness is high, but it is used with caution in patients with intestinal obstruction, heart and kidney dysfunction, and hypertension.
B. Oral 33% magnesium sulfate: 10 ml / time, 1 time / 2 hours 1 day before surgery, generally 5 ~ 15g total day. After taking 33% magnesium sulfate, drink 5% sugar saline or 1000 ml normal saline. Diarrhea occurs after about 30 to 45 minutes. Sodium sulfate can also replace magnesium sulfate, which is slightly less irritating to the intestines. This preparation method is more suitable for patients with incomplete intestinal obstruction.
C. Oral castor oil: 1 day before surgery, 30 ~ 45ml / time, drink plenty of water later, diarrhea after 3 ~ 4h. It can also be applied simultaneously with saline enema and liquid diet. This method can have nausea, vomiting, and abdominal pain.
D. Oral mannitol method: Oral administration of 20% mannitol 250 ml 1 day before surgery, followed by oral administration of 1000-1500 ml of physiological saline, and diarrhea can be produced after about half an hour. However, it should be noted that mannitol can produce flammable gases after decomposition of bacteria in the intestinal tract. If the treatment uses high frequency electricity, the spark may cause the gas to explode, resulting in intestinal perforation and intestinal damage. The inert gas CO2 or N2O can be used to replace the gas in the intestinal tract to prevent accidents.
E. Saline enema: colonic lavage 1 day before surgery, can also be combined with oral laxatives.
3 Intestinal preparation in the emergency: aiming to clear the contents of the lumen of the proximal obstruction in order to carry out the first-stage intestinal anastomosis. Only the upper part of the intestine is cleaned to be safely anastomosed. In the case of colonic hemorrhage, the intestinal lumen can be cleaned during surgery to make it easier to identify the bleeding. According to different parts of obstruction, design the method of lavage discharge of intestinal contents during surgery:
A. Sigmoid colon or left colon surgery: the root is removed through the appendix, and the Foley catheter is inserted into the opening and left as a flushing fluid inlet. Carefully dissociate the left colon, insert 2 curved aortic forceps above the obstruction, perform a purse-string suture on the anterior wall of the intestine, insert a threaded tube for the anesthesia machine to the proximal end, and connect the plastic waste under the operating table to the other end. Bag or cartridge, rinse with ionic solution to clear water. The distal part of the tumor is also free, and it is cleaned from the anus to prevent contamination and damage to the intestinal wall.
B. Rectal anastomosis: For rectal cleaning, the patient takes the bladder lithotomy position. After the free rectum, the rectum is placed under the tumor. The balloon Foley tube is directly inserted into the anus to wash the lower rectum, and the water is cleared repeatedly. In addition, after rinsing, the rectum can be further disinfected with benzalkonium bromide (new chlorhexidine) or diluted iodine, which helps to reduce the incidence of anastomotic leakage.
(3) Principles of Surgery: Radical cure is to achieve the purpose of cure. The surgery that cannot be cured is palliative surgery. The radical surgery needs to remove the corresponding lymphatic drainage area. As for how many colons and corresponding lymphoid tissues are removed, it should still rely on individualized design. The correct scope of colon resection depends largely on the extent of lymphatic drainage in the area to be removed and the extent to which the vessel should be removed. The more the vessel resection, the more the intestine is removed.
1 The scope and procedure of radical resection of the right colon: a typical right colon resection in the right colon cancer, the cecum, ascending colon, hepatic flexion and proximal transverse colon-ilectal artery, right colonic artery and middle colon artery The right branch was ligated and cut, and the distal ileum was removed 10 cm. Some people think that the true radical surgery should remove the trunk of the middle cerebral artery and try to be close to the superior mesenteric artery. Thus, the resection of the transverse colon is increased, and only the distal 1/3 of the transverse colon remains as an anastomosis.
The cecum and ascending colon need to be ligated back to the colonic artery. The right colonic artery and the transverse colonic middle artery are near the root. The resection of the intestine depends on the individual condition. Sometimes the cecal can retain the colon right curvature, but sometimes it is impossible. The hepatic collateral colon tumor, the right branch of the middle cerebral artery and the right colonic artery were ligated and retained in the ileal artery to determine the length of the intestine segment. See the typical range of resection.
Surgical procedure: free cecum, right colon and colon right circumcision, incision or electrocautery to open the right colon collateral peritoneum, up to the hepatic flexure outside the cecum, separate the greater omentum into the small omental sac, push the colon to the midline Pulling on the left side, pushing away the loose interstitial tissue of the wound, see the inner leaves of the mesentery and the blood vessels, and the dorsal wall of the dorsal side. There are spermatic (or ovarian) blood vessels, ureters and duodenum descending. After the colon is completely free, the roots of the resected blood vessels are ligated and cut, and the colon and the ileum at the end of the severing site are separated from the valve 10 to 15 cm, including the corresponding mesenteric vessels, and the ileum, transverse colon end or end end anastomosis. The end-to-side anastomosis is located 2 to 3 cm from the end of the closed transverse colon.
2 The scope of radical resection of transverse colon cancer: right lateral colon cancer has been included in the right colectomy, splenic squamous cell carcinoma included in the left colon, and between the two for transverse colon resection or enlarged left or right colectomy . The target of resection is the large transverse membrane and the attached omentum, the middle colon artery and the corresponding lymphatic reflux. Firstly, the omentum on the large curved side of the stomach is separated, and the sacs on both sides of the colon and the sacral colon ligament are separated, and the transverse colon is pulled downward. The left curved person should pull up the wound to achieve good exposure. If the transverse colon is long and there are not many transverse colons removed, it is not necessary to separate the sacral ligament, and the posterior end anastomosis is removed to repair the transverse mesenteric membrane (Fig. 7).
3 The scope of radical resection of left colon cancer: the peritoneum is separated from the sigmoid mesentery, and the colon is pushed to the medial side (right side) along the paracolic sulcus. The left ureter is first seen, and the left spermatic cord and the lower aorta are pushed outward. The iliac artery and vein, then free spleen, open the gastric colon retina and expose the transverse colonic middle artery, and separate at the left branch junction, in order to remove the distal segment of the transverse colon. Careful separation of the spleen colon to avoid tearing the ligament of the ligament of the ligament and bleeding, resulting in the inability to do splenectomy. Free the left colon and the peritoneum, expose the inferior mesenteric vein and separate the splenic vein, carefully ligature and cut off, keep the junction of the sigmoid mesentery and the left colon blood vessels, and see the duodenum in the third and fourth parts of the duodenum. The jejunum is pulled down to the aortic bifurcation, the inferior mesenteric vein is exposed, and the ligation is carefully ligated. At the same time, the para-aortic lymph nodes are removed, and then the intestine segment is cut. According to the conventional end-to-end or end-to-side anastomosis, lateral anastomosis can also be performed. The peritoneal fissure was repaired (Fig. 8A). Part of the transverse colon or sigmoid colon is retained (Fig. 8B).
4 Sigmoid colon cancer resection range: Separation of the sigmoid colon rectum junction, the patient takes the head low position to accommodate the separation and ligation of blood vessels, most of which are located in the sigmoid colon, separating the blood vessels from the root, that is, under the left colonic blood vessels, ligation of the mesenteric vascular sigmoid colon, The superior rectal anastomosis is equivalent to the level of the iliac crest (Figure 9).
5 The choice of radical cure and palliative resection: It was originally thought that there was a palliative operation in which the transfer could not be cured. For this reason, in some cases, there are often different outcomes, and thus there are different choices. It has been reported that in patients with fixed tumors, there is still more than 1/4 of 5-year survival rate after radical resection. The peritoneal sacral surgery is performed in patients with loose nodules or liver metastases, but it must be frozen to confirm whether it is a travertine powder foreign body granulation nodules, but not metastasis or liver metastasis, especially single metastatic nodules. Radical resection.
(3) treatment of metastases: 15% to 20% of colon cancer patients with distant metastases, of which 30% to 40% had undergone so-called radical surgery, 80% found that within 3 years of surgical treatment, the most visible site is liver. Followed by abdominal cavity, pelvic cavity, retroperitoneal and lung, most of which were multiple metastases, and a few surgical resections were feasible.
1 liver metastasis: general resection, frozen local chemotherapy or systemic chemotherapy, due to liver metastases can be obtained after the mid-term survival of 20 to 40 months. The 5-year survival rate can reach 25% to 48%. Long-term tumor-free survival can reach 12% to 19%. Generally, the longer the time from the liver metastasis, the longer the prognosis is. A few more than 4 metastases are asymptomatic. Repeated resection of metastatic cancer has been reported in careful selection of cases.
A. Hepatic artery chemotherapy: Colon cancer is one of the main primary tumors of secondary liver cancer. For those who are not suitable for surgical resection, such as multiple metastases, liver function decompensation and poor general condition, hepatic arterial chemotherapy can be applied. The application method is not only the intraoperative catheterization, the chemotherapy of the kit, or the percutaneous transluminal catheterization of the skin, and the purpose of targeted local chemotherapy. Recently, continuous infusion chemotherapy with a drug pump (box) has also been used.
Uchida compared a systemic and hepatic artery administration to a prospective study of liver metastases from colon cancer. The results showed that hepatic artery administration was superior to systemic therapy; even for patients who had received fluorouracil-based colon cancer liver metastasis systemic chemotherapy, FUER was used. /Fluorouracil and fluorouridine (FUDR) / calcium leucovorin / dexamethasone (DXM) regimen, the effective rate is still 30% to 50%, the average survival time is more than 1 year. Despite this, the choice of drug doses for hepatic arterial infusion in the treatment of liver metastases from colon cancer has not been determined in the treatment, and randomized studies on the effects of arterial and systemic administration on survival are still underway.
In recent years, the technique of catheterization of the left subclavian artery and the catheterization of the catheter has not only affected the continuous perfusion of the drug, but also affected the quality of life of the patient. This has taken a step forward in technology and solved the unsustainable path of the transarterial artery. Sex. Research and development are still ongoing.
Liver metastases naturally existed in the untreated group for an average of about 16 months. It is generally considered that the effect is better after resection, and 15% to 25% are resectable. Preoperative and intraoperative estimates of liver metastases involve the possibility of resection. The following methods: 1 preoperative angiography to understand the scope and possibility of resection; 2 intraoperative ultrasound, due to direct contact with the liver, less signal loss, often more than the palpation can find metastases, and the positioning is accurate, the guidance is clear, so there are conditions Should be used as a routine, for those who are suspicious of metastasis, can help to confirm the diagnosis.
B. Cryotherapy: Intraoperative ultrasonography can not only find the presence or absence of metastases, but also guide the treatment. It is treated with a frozen liquid probe of flowing liquid nitrogen. This method has been used for the treatment of malignant tumors in the skin, rectum and prostate. It can also be used for liver tumors to form an ice hockey at the tumor site. 28% of Ravikumar and other 32 patients were followed up for 5 to 60 months without tumor. Onik 18 patients could not be resected, and 14 patients survived to a recurrence of 21.4 months, of which 2 survived.
Matsui summarized the success rate of different methods for detecting liver metastases, 58% for ultrasound, 63% for CT, 27% for selective angiography, 50% for hepatic artery angiography, and CT with arterial portography (CTAP). For 84%, CTAP means the most.
C. Liver tumor resection: The effect of this treatment for colorectal metastases has been affirmed. A single metastase was found to be resected with colon surgery. The Mayo Clinic reported 60 cases, 2/3 were single, and after surgery. 42% lived for 5 years, the total 5-year survival rate reached 25%, and multiple multiple metastases also had long-term survival. The cure rate can reach 20% to 25%.
2 ovarian metastasis: ovarian metastasis is a common problem in colon cancer, namely Kurkenberg tumor. It is generally believed that the transfer is found to be 2% to 6% after surgery, and the transfer is 2% under the microscope. The issue of preventive resection of the ovaries has attracted attention and opinions are inconsistent. It seems that it is advisable to have a forward-looking study to make further decisions, especially for functional ovaries.
3 Lung metastasis: the presence or absence of lung metastasis is of great significance for the palliative or radical treatment. Although there are a certain number of lung metastases, it is found that especially the single person is resected at the same time. The original stove is difficult to cure the resection or extensively involve other tissues and organs.
(4) treatment of intestinal obstruction: colonic obstruction is easier to see in the left colon cancer, because the ileocecal valve is often closed, so the intestinal contents can often enter, but can not reversely into the small intestine, the formation of closed obstruction, clinically obvious expansion The colonic intestine type, X-ray plain film can also be seen in the liquid level of the colorectal area, due to easy formation of closed sputum type, gastrointestinal decompression effect is not good, combined with blood supply is not as rich as the small intestine, easily lead to local intestinal wall necrosis or perforation, Therefore, once diagnosed as colonic obstruction, early surgical treatment should be performed.
Preoperative bowel preparation is often not ideal, more than intraoperative plus decompression and wash. After cleaning, the colon end-to-end anastomosis is routinely cut. The irrigation tube can be removed or temporarily retained for cecal fistula to facilitate decompression.
The surgical method of colon obstruction depends on the general condition, the degree of bloating and the location of the obstruction: if the patient is in poor condition, the abdominal distension is severe, and the gastrointestinal decompression can not be relieved, especially in the left obstruction, the transverse colon or the proximal colostomy can be performed first. In the short-term, the tumor intestine is removed in the second stage. After the anastomosis is healed, the general condition is improved and the sputum retraction is performed to restore the intestinal tract; if the tumor is necrotic and perforated due to intestinal obstruction, it is not suitable for further surgery after resection of the cancer. The external end of the ostomy, after the general condition improved, and then the second phase of surgery, repair ostomy, restore intestinal connectivity; for patients with obvious toxic shock, difficult to bear large surgical trauma, the cancerous part can be external, until the shock period After further control, the two segments of the intestine segment of the lesion can be externally removed from the abdominal cavity. After the general condition is improved, the second operation is performed.
(5) Laparoscopic colon surgery: Laparoscopic colon surgery began in 1991, and laparoscopic colon surgery requires much higher technical requirements than laparoscopic cholecystectomy. Although laparoscopic surgery is currently available for any part of the colon, including benign and malignant lesions of the colorectal, there is considerable controversy about the use of laparoscopic radical resection of malignant tumors.
1 Surgical indications: There is no consensus yet. The indications and case selection depend mainly on the experience of surgeons in laparoscopic surgery. Of course, not all lesions can be removed with laparoscopy, such as large and advanced tumors involving adjacent organs, and obese patients are more difficult to perform laparoscopic surgery due to tumor infiltration or severe adhesions caused by previous surgical procedures.
2 Difficulty of operation: The difficulty of different parts and different types of laparoscopic colorectal surgery varies greatly. The right colon and sigmoid resection are less difficult, and the transverse colon resection is the most difficult. So now about 2/3 of laparoscopic colorectal surgery is right colectomy and sigmoid resection, followed by less-use left colectomy, and the least applied is transverse colectomy.
3 operation points: laparoscopic colorectal surgery generally requires 4 small incisions of 5 ~ 12mm; put the corresponding size of the cannula, so that the endoscopic anastomat can be placed through the endoscopic anastomosis, 5mm can be placed into the separation forceps, Scissors, electric hooks and aspirator devices (Figure 10).
Malignant tumor surgery should abide by the basic principles of tumor surgery. It is necessary to remove the proximal and distal intestines and the lymphatic tissue, and to disconnect the blood vessels from the roots. Try to avoid direct manipulation of the cancer and separate it along the natural tissue interface.
The tiny blood vessels can be directly electrocoagulated and then cut off. The larger blood vessels should be cut off after the titanium clip on both ends. After the intestinal tube is free, a small incision can be made and the intestine can be taken out to ligature the main blood vessels in vitro.
Disconnection and anastomosis of the intestine can be done in vivo or in vitro, and a stapler must be used in the body. Generally, after the completion of the intestinal tract, a small incision of 3 to 5 cm is required for the removal of the specimen. The length of the incision should be determined according to the size of the tumor. If the incision is too small, the specimen is easily squeezed and the tumor cells are grown. If the incision is too long, the meaning of laparoscopic minimally invasive surgery will be lost. Some sigmoid colon and rectal specimens can also be removed through the rectum and anus.
According to whether the intestine is free, the vascular ligation and the intestinal anastomosis are completed in the abdominal cavity, there are laparoscopic colorectal surgery and laparoscopic assisted colorectal surgery.
Laparoscopic colorectal surgery is a minimally invasive procedure. The basic principles of treating the original disease have not changed during the operation. Laparoscopy has been accepted for the treatment of benign colorectal diseases, but it is controversial to use laparoscopic resection of colorectal malignancies. Although there have been prospective studies supporting the resection of laparoscopic colon malignancies, it is still unclear whether laparoscopic surgery will increase the recurrence of local and systemic cancer, so prospective, randomized, and multicenter clinical observations are needed. the study.
(8) Pathway and prevention of cancer cell proliferation during operation: During the operation, cancer cells can spread through the intestinal wall, intestinal lumen, vein, lymph, or fall off the peritoneum and anastomosis, so it is necessary to take necessary Precautions to improve the surgical outcome (Figure 11).
1 operation should be gentle, to avoid squeezing and touching cancer. Firstly, the intestinal tube of the tumor is ligated with a cloth tape. If it is technically possible, the root canal is ligated before dissection and separation of the affected intestine. The intestinal lumen is washed with anticancer solution before the anastomosis.
2 The incision of the intestine should be 10cm away from the cancer to ensure that there are no cancer cells remaining at the broken end, avoiding local recurrence and spreading through the intestinal wall.
3 From the beginning of the investigation, an intravenous infusion of anticancer drugs can be given, and fluorouracil 10 mg/kg body weight can be used to reduce the dissemination of menstrual blood.
4 The needle thread used in the operation is soaked with anticancer drug solution to reduce the wound implant, and partially washed with anticancer liquid or hypotonic liquid (sterile water) to destroy the cancer cells. The instrument glove should be replaced before closing the abdominal cavity.
Strict adherence to the principles of cancer surgery during surgery can significantly improve the 5-year survival rate of colon cancer radical surgery.
(9) Postoperative complications and management:
1 postoperative massive hemorrhage of colon cancer: From an anatomical analysis, no matter which kind of colon surgery, the blood supply artery is exposed clearly, can be operated under direct vision. Therefore, after colon cancer surgery, hemorrhage is generally less common. However, in the operation of the left spleen colon cancer, if the spleen colonic ligament is short, the spleen may be accidentally injured and cause bleeding. Or the tumor invades to the outside of the mucosa and adheres to the spleen, causing bleeding when separating the spleen.
In addition, spleen vascular ligation is not true, or blood stasis after the electrocautery cauterization of blood vessels larger than 3 mm may also cause massive bleeding. Therefore, the emphasis on ligation is indeed in operation, and the operation specification is careful, which can reduce the occurrence of this complication to a certain extent.
The drainage tube should be placed after operation to observe the drainage volume. If there is more drainage, or if there are clinical symptoms such as shock in the early postoperative period, you should be alert to the possibility of major bleeding. Treatment can generally be conservative observation, active blood transfusion, fluid replacement and other anti-shock treatment. If the amount of bleeding continues to increase or the symptoms of shock cannot be improved, hemostasis must be explored again. Abdominal drainage tube is an important channel to observe the presence or absence of abdominal bleeding, and should be properly protected against falling off.
2 ureteral injury: in the left axilla, the sigmoid mesenteric ureter is ureter, ligation of the sigmoid colon artery or upper rectal artery is easy to accidentally injured. After entering the pelvic cavity, the ureter enters the anterior side of the ischial spine plane, and walks through the connective tissue above the levator ani muscle to the bladder and enters the posterior wall of the bladder. These anatomical and traversing characteristics of the ureter are the basis for easy injury during surgery.
If the ureter is bilaterally ligated, there will be no urine after surgery, and the diagnosis will be confirmed after acute hemorrhagic shock. If only unilateral ligation, urinary excretion can be blocked, only the affected side is painful, but it is easy to be incision pain. Concealed, or mistaken for postoperative general reactions. B-ultrasound can be found in the affected side of the kidney effusion, ureteral dilatation, conventional dose of excretory urography is not developed in the affected side of the kidney, high-dose excretory urography shows that the renal effusion of the affected side and the ureter above the ligation site is significantly dilated, ureteroscopy Examination revealed a ureteral occlusion or chronic stenosis at the ligation site.
Intraoperative reduction and prevention of ureteral injury should pay attention to: A. If bleeding occurs during surgery, it should be pressed with gauze in time, wash the bleeding, prevent blind large tissue clamping and ligation, should be seen under direct vision after bleeding point Line processing. B. When cutting the rectal ligament, the anterior rectal and rectal space should be released to the lateral ligament plane of both sides, the lower end of the bladder and the pelvic ureter should be retracted, and the rectum should be lifted to the opposite side. The wall is divided into posterior and forward ligaments to cut the lateral ligament. C. The tumor is large, and there are many adhesions to the surrounding tissue, or patients who have undergone pelvic surgery and radiotherapy, it is best to do urography or ureteroscopy before surgery to facilitate the identification and protection of the ureter during surgery.
The principle of treatment of ureteral injury is to reconstruct the urinary pathway and protect kidney function. If it can be found in time, the ureteral end-to-end anastomosis should be performed immediately, and double J tube should be used for drainage. On the one hand, the double J tube can support the ureter as an internal stent to prevent scar stenosis during the healing process; on the other hand, it can be drained smoothly, and no extravasation, infection and urinary fistula can occur, and the pain caused by the indwelling drainage tube can be avoided. If it is found that it is not timely, the extravasation of urine causes infection, oozing more, etc., it is not appropriate to use double J tube. Temporary urinary diversion can be done temporarily, and ureteral transplantation or replacement surgery should be performed after infection control.
Once the ureteral ligation is clearly performed after surgery, it is necessary to seek surgical exploration as soon as possible, and loosen the ligation. If the ureter is ligated or severed on the operating table, the ureteral continuity can be restored by immediate release or anastomosis; if the postoperative extension is found, most cases are organized. Degeneration, local excision and ureteral anastomosis should be performed; if conditions are limited, it is impossible or not suitable for surgical repair, and the ureter or the affected side of the renal pelvis should be performed first to achieve renal drainage and protect kidney function. Such as distal ureteral injury defect, feasible ileal ureter.
3 anastomotic leakage: anastomotic leakage is one of the serious complications of colon cancer surgery, if not treated in time, the mortality rate is extremely high. The incidence of anastomotic leakage in foreign countries is reported to be 4% to 25%, and domestic reports are between 5% and 10%. The occurrence of anastomotic leakage is related to systemic conditions, preoperative bowel preparation, surgical operation, anastomotic blood supply and tension, quality of anastomosis, pelvic infection and poor drainage. It often occurs 4 to 9 days after surgery. The left colon is poorly transported due to poor blood supply. The stool contains more bacteria. Postoperative anastomotic leakage is more common. Right colon resection is relatively rare.
A. Causes: a. The patient's systemic nutritional status is poor: colon cancer occurs mostly in middle-aged and elderly people, often combined with chronic wasting diseases such as diabetes and cirrhosis, and the tumor itself causes excessive consumption of patients. These all make the body's repair and anti-infective ability seriously reduced, resulting in poor healing of the anastomosis. Intestinal obstruction and intestinal dysfunction also lead to poor systemic nutrition, weight loss, lack of protein and various nutrients, directly affecting the repair function of the tissue and the immune function of the body. b. Intestinal obstruction: Most of the left colon cancer is accompanied by different degrees of obstruction. Preoperative bowel preparation often fails to clean the intestine. When emergency surgery is needed, it is difficult to completely decompress during surgery because of the high bacterial content in the intestinal cavity. For example, postoperative intestinal feces and gas accumulation can lead to an increase in anastomotic tension, and anastomotic contamination also increases the incidence of anastomotic leakage. c. Intestinal anastomosis blood supply is poor, tension is large: good blood supply is an important factor to ensure the normal healing of the anastomosis, excessive free intestinal ductal mesenteric or excessive resection of adipose tissue around the anastomosis of the colon, injury Colonic mesangial vessels, which are not sufficiently tight or too sparse, can affect the healing of the anastomosis. Intestinal anastomosis is performed on the intestines of congestion, edema, severe infection or residual tumor. Postoperative general intestinal wall tissue healing is poor, and anastomotic leakage is prone to occur. d. Early venting: Individual patients experiencing venting early after surgery often lead to anastomotic leakage. Early venting of such patients is not inadequate for bowel preparation and may be caused by individual patient differences. e. Electrocoagulation injury: Electrocoagulation is an electrocautery and electrocoagulation that mainly destroys or coagulates the tissue structure by local heating, and electrically cuts the vaporization of the tissue by continuous sine waves. When the electrosurgical knife is applied on a predetermined target tissue, it can also cause damage to the surrounding tissues and organs, mainly the "skin effect" in the closed body cavity, that is, the current flowing in the human body is carried out along the minimum path of resistance. The current in these conductors moves toward their surface, causing intestinal damage. Since the high frequency current return path in the body is difficult to predict, it is not easy to avoid such damage. Choosing the right power reduces burns in surrounding tissues.
B. Prevention: a. Highly responsible: the surgeon must be highly responsible to the patient, take every factor that affects the healing of the anastomosis seriously, and reduce the occurrence of anastomotic leakage as much as possible. b. Adequate bowel preparation: It is the main measure to prevent the occurrence of anastomotic leakage. Before the operation, it is necessary to ensure that the intestines are empty, no liquid is stored, and no residue of feces is allowed. Absolutely, the anastomosis is not carried out in the case where the intestines are full of feces. For patients with incomplete obstruction before surgery, a less slag liquid diet should be given 4 to 5 days before surgery, and parenteral nutrition support should be given, or enteral nutrition preparations should be taken 4 to 5 days before surgery. Clean enema can be performed 1 day before surgery. In the case of good bowel preparation, if the stapler is anastomosed during surgery, when the stapler is withdrawn from the anus, there should be no intestinal contents flowing out along the stapler.
C. Treatment: Once an anastomotic fistula is diagnosed, it should be treated as soon as possible with active and effective treatment measures to prevent more serious complications and endanger the patient's life. First of all, we should improve the general condition of patients, strengthen nutritional support therapy, improve the body's ability to resist infection, and maintain water and electrolyte balance. Because abdominal analgesia caused by anastomotic leakage is mostly mixed infection, it is recommended to use antibiotics in combination, especially anti-anaerobic drugs. Actively treat various combined diseases, especially to control blood sugar levels. It is strictly forbidden to use various anticancer drugs that affect the immune function of patients.
Even if the right colon resection occurs, most of them can be cured by non-surgical treatment, especially the improvement and development of total parenteral nutrition support treatment, and the cure rate of anastomotic leakage is greatly improved.
Anastomotic fistula occurred after left colon resection, heavy intra-abdominal contamination, and prominent peritoneal inflammation. Therefore, placement of the abdominal drainage tube, close observation of changes in drainage volume, taste, color, has a very important role in the early detection of anastomotic leakage, generally the drainage tube is left for 6 to 7 days. Once an anastomotic sputum occurs, if the symptoms are aggravated after antibiotic treatment, the symptoms should be aggravated, and the proximal enterostomy should be performed in time. The double-tube stoma is better, and the circulation can be fully and can be washed through the distal end to clean the leak. The mouth promotes healing. If the patient's condition is poor, the condition is not allowed to treat the anastomotic lesion at the same time, and the second-stage treatment should be performed after the limitation of the infection of the leaking mouth. In colon cancer surgery, if the anastomotic suture is not perfect, and the patient's condition is poor, it is estimated that there is a possibility of leakage. It is necessary to perform an enterostomy in the upper part of the anastomosis to protect it.
4 postoperative incision infection: intraoperative colorectal contents may overflow, postoperative incision infection rate is 5% to 10%, the more common pathogens are often resident bacteria such as E. coli. Incision infection is the most common complication after surgery. If it is not handled properly, it may lead to prolonged hospitalization, increase medical expenses, and even cause sinus that will not heal for a long time.
A. Reasons: a. Systemic factors: malnutrition and other factors that contribute to the weakening of the systemic immune defense mechanism. If the patient has diabetes, chronic kidney disease, hypoproteinemia, uremia, arterial occlusive disease, or long-term hormone therapy, the chance of infection in the wound is greatly increased. b. Surgical factors: Prolonged operative time may also increase the infection rate of the incision. Prolonged surgery increases the possibility of bacterial contamination and also leads to disorders of systemic physiological function. c. Environmental factors: Infections in hospitals occur from time to time. Therefore, ward management should be strengthened, and the principle of aseptic operation should be strictly observed to minimize the incidence of wound infection. d. Local factors of the wound: such as blood circulation disorder in the local tissue of the incision; the formation of hematoma and dead space provides a good medium for bacterial growth and reproduction; necrotic tissue or foreign body residue; postoperative incision drainage is too long to cause retrograde infection, especially It is the cigarette drainage, exuding to the outermost dressing of the incision, but not changing the medicine in time, due to the siphon effect of cotton fiber, leading to retrograde infection; incision fat liquefaction, infection and necrosis in obese patients; colostomy distance from abdominal wall surgical incision The distance between the two is relatively close, or the fake anal pocket film is used improperly, so that the feces are missed and the abdominal wall incision is contaminated; sometimes the tension line is sutured and knotted, and the false anal pocket film is not firmly adhered, and the wound infection is also prone to occur.
B. Prevention and treatment: a. Correct the patient's anemia, hypoproteinemia, improve the general condition, properly treat the combined disease, and rational use of antibiotics can reduce the infection of the wound. b. In the operation, hemostasis should be stopped to prevent the formation of hematoma in the incision; the incision should be thoroughly washed to remove the adipose tissue that may be necrotic; the suture should be properly selected to avoid over-tightening and formation of an ineffective cavity, the incision is long, the patient is old, and the nutritional status is not The best can do the tension stitching. c. Maintain a smooth gastrointestinal decompression after surgery, properly bandage the abdomen, and try to reduce the factors that induce a sudden increase in intra-abdominal pressure.
5 Incision rupture: Incision rupture mostly occurs 1 to 2 days after suture removal, and a small number of patients can occur in a few days after surgery, even 2 weeks after surgery. Most patients felt pain in the incision tear after the abdominal pressure increased, and then relaxed. The sound of the slit cracking is often heard. The rupture of the incision is sometimes only one or more layers of the abdominal wall, or it may be completely ruptured. Chronic rupture often leads to the formation of incisional hernias.
A. Causes: The systemic factors that cause the incision to rupture are similar to the systemic factors that cause infection in the incision, but rupture of the incision is often rare in younger patients. Incision hematoma, severe tissue damage, formation of ineffective cavity during suture, and entrapment of the omentum in the peritoneal suture space may lead to incision rupture. In addition, the anesthetic effect is poor, or the anesthesia is not good, and the premature stop of the muscle relaxant can cause the incision to split.
B. Prevention and treatment: timely use of abdominal bandage after surgery is important to prevent incision cracking. For a completely ruptured incision, a second-stage suture should be performed on the premise that the granulation tissue and the wound are fresh. The slits are small or not full-thick, and the incision is pulled with a butterfly tape. The butterfly tape must be disinfected with iodine to keep the incision clean.
6 intestinal obstruction: postoperative intestinal obstruction is a common complication of colon cancer radical surgery, and mostly simple adhesive intestinal obstruction, prevention is more difficult. Postoperative intestinal adhesions and obstruction have large individual differences, and their formation is mainly related to surgery.
A. Reasons: The main causes of intestinal obstruction in colorectal surgery are as follows: a. The suture is sutured on the peritoneum, and the intestine is angled to form a mechanical intestinal obstruction. b. Infiltration of fibrinogen on the surface of the intestine crosslinks to form fibrin strands, causing mechanical intestinal obstruction. c. Postoperative autonomic nerve and corresponding intestinal segment blood vessels are cut, diffuse peritonitis and other causes of paralytic ileus. d. Sometimes after the tumor operation in the cecal area, due to the change of normal anatomical position, intestinal fluid secretion, with the increase of pressure, the physiological effect of the ileocecal valve is weakened or disappeared, etc. may also cause poor drainage and intestinal obstruction. e. The peritoneal rupture of the pelvic floor forms an intestinal tract that causes intestinal obstruction. During the excision and removal process, the posterior peritoneum should be left as far as possible, and the peritoneum of the pelvic floor should be closed, which can reduce the occurrence of adhesive intestinal obstruction and pelvic floor intraperitoneal hernia. If the posterior peritoneal closure is not satisfactory, it may be considered not to suture to prevent the occurrence of spasms. f. Intestinal regurgitation during intestinal resection and enterostomy, and the small intestine enters the internal iliac formed by the pores. g. When the sigmoid colon is removed too much, a large cavity appears after the bladder. If the small intestine falls into the surrounding area, it may form an obstruction.
In 1948, Ogiie first described acute colonic pseudo-obstruction (ACPO), pointing out that this complication may be caused by vagal dysfunction in the distal colon of 骶2～骶4. There is a typical clinical manifestation of acute colonic obstruction. X-ray shows a "truncation sign" of the splenic flexure and a high degree of proximal colonic dilatation and a small gas-liquid flat surface. Need to be diagnosed after barium enema or colonoscopy to exclude mechanical intestinal obstruction. After the sigmoid colon lavage decompression, the gas and feces in the intestines were excreted, and the symptoms of obstruction were quickly relieved. If the above methods are ineffective, cecal fistula or external fixation may be selected, and severe left colon resection may be feasible.
B. Prevention and treatment: careful operation during operation, wet gauze should be used as much as possible in the intra-abdominal operation, and a large amount of saline should be used to flush the operation area before the end of the operation. Measures such as encouraging and supervising patients to properly turn over and get out of bed early are beneficial to the operation. Reduce the incidence of intestinal obstruction. In recent years, the application of sodium hyaluronate has played a role in preventing postoperative intestinal adhesions.
Paralytic ileus can be relieved by conservative treatment, including: fasting, water, intravenous rehydration, anti-infection, gastrointestinal decompression, etc. Mechanical intestinal obstruction according to its treatment principles to choose the appropriate measures, if there is a blood circulation disorder, should be immediately surgical exploration.
7 deep vein embolization and pulmonary embolism: elderly patients are hospitalized for a long time, or the surgical position makes the leg muscles compressed for a long time, prone to deep vein thrombosis, especially in patients with sigmoid surgery. Prevention: A. Strengthening activities: such as lifting legs in bed, using elastic stockings and getting out of bed early. B. Apply intermittent pressure to the calf in the calf during surgery. C. Application of anticoagulant: low-dose heparin, levulin, or aspirin after surgery. Dextran has the same effect as heparin in preventing pulmonary embolism, but it is not as good as heparin in the prevention of deep vein thrombosis of lower extremities. The application of elastic stockings and intraoperative air pressure sleeves is essential for early activities.
2. Nutritional support for patients with malignant tumors should be given nutritional support treatment as soon as possible.
(1) Assessment: 1 whether the patient can eat through the gastrointestinal tract; 2 whether the energy provided by the gastrointestinal tract can meet the needs of the patient; 3 whether the patient's gastrointestinal function is disordered; 4 whether the patient has other diseases, such as heart failure , kidney failure and other diseases.
(2) Nutritional methods: Nutritional therapy should select appropriate ways and methods according to the patient's condition and gastrointestinal function.
1 enteral nutrition support: patients with certain gastrointestinal function should use enteral nutrition support. Nutrients are absorbed through the intestines and portal veins, in line with normal physiological conditions, can improve and maintain the structural and functional integrity of intestinal mucosal cells, maintain intestinal mucosal barrier, reduce intestinal bacterial translocation and intestinal infection. Common diets include mixed milk and essential diets. The supply route can be oral, gastrointestinal or nasal feeding.
2 parenteral nutrition support: patients with gastrointestinal dysfunction or failure, or when oral nutrition can not meet the needs of the body, should be given parenteral nutrition support treatment. The vena cava and peripheral veins are often used to provide nutrients to the patient.
A. Nitrogen source: The normal human protein requirement is 1g/(kg·d). The postoperative patient needs 1~1.5g/(kg·d), and the protein should account for 10%~12% of the total energy. The protein is provided by a compound amino acid. Amino acids provide a substrate for the body's synthesis of proteins and other biologically active substances. Postoperative patients with high liver amino acid infusion (branched chain amino acid) can reduce muscle catabolism, promote liver and organ protein synthesis, and help the body restore metabolic function in extrahepatic tissues.
B. Energy: Glucose typically provides between 60% and 75% of the total energy, with the remainder being powered by a fat emulsion injection. The metabolism of glucose must depend on the presence of insulin. Therefore, patients with insulin deficiency due to diabetes and surgical trauma must be supplemented with exogenous insulin to ensure full utilization of glucose. In addition to providing the energy required by the body, the fat emulsion injection also provides the body with polyunsaturated fatty acids required for the metabolism of biofilms and bioactive substances. The fat emulsion injection is rapidly diluted into the blood, and is hydrolyzed by the lipoprotein esterase in the capillary endothelial cells of the extrahepatic tissue to release free fatty acids (FFAs) for utilization by the tissue cells, and the remaining residual particles are taken up by the liver tissue. Decomposes, metabolizes under the action of hepatic lipase, and re-esterifies to form adipose tissue storage of the body. The amount depends on the length of the fatty acid and the content of the polyunsaturated fatty acid and the composition of the phospholipid.
A large number of experimental studies have shown that high-dose or long-term use of long-chain fat emulsion injection can affect the body's reticuloendothelial system and interfere with plasma lipoprotein metabolism; medium-chain fat emulsion injection has in vivo hydrolysis, oxidative clearance, and does not depend on carnitine Translocation and small interference with plasma lipoprotein metabolism are considered to be ideal energy sources.
Resting energy consumption (REE) can be calculated according to the Harris-Benedict formula.
Female: REE (kcal/d) = 65.51 [9.5 x body weight (kg)] [1.7 x height (cm)] - [4.7 x age (year)].
Male: REE (kcal/d) = 66.5 [13.8 × body weight (kg)] [5.0 × height (cm)] - [6.8 × age (year)].
After surgery, the actual energy needs to be higher than the rest state due to trauma and stress response.
(3) Complications and prevention:
1 aspiration pneumonia: patients with weakness, coma, cough, vomiting are prone to aspiration during tube feeding, resulting in lung infection. Therefore, when feeding, attention should be paid to the position of the feeding tube and the speed control of the perfusion.
2 diarrhea: a common complication of enteral nutrition support treatment. Most of the long-term fasting gastrointestinal digestive function has not fully recovered, or the diet is high, not fresh or low temperature. Early eating should start with small, easily digestible fluids, semi-liquid foods; ready-to-eat foods, temperature with body temperature; with food utensils should be digested; slow down the rate of perfusion and add anti-spasmodic or astringent drugs to the diet Control diarrhea.
3 metabolic disorders: hypoglycemia occurs when the enteral nutrition support is stopped, and other means of supplementing glucose after slow stop perfusion or deactivation can often be avoided. Hyperglycemia mainly occurs in the use of elderly or pancreatic patients. Therefore, patients who cannot tolerate high glucose should reduce the amount of sugar or give insulin to control blood sugar, and strengthen the monitoring of blood sugar. In addition, parenteral nutrition support can still occur water and electrolyte disorders, acid-base imbalance and azotemia, etc., should pay attention to the speed of infusion, the ratio of glycolipids, strengthen various tests, timely detection and timely treatment.
4 fever: When the fat emulsion is quickly input, the patient will have fever. The heat generated by 1g of fat milk is twice as high as that of glucose. When the supply per unit time exceeds the consumption of the body, the body temperature rises. Therefore, the fat emulsion input is controlled within 4ml/min to avoid continuous loss of fat emulsion and hypertonic glucose.
5 liver damage and phlegm: mostly due to the different pathways of nutrients entering the liver and normal pathways. In particular, the incidence of long-term parenteral nutrition support is high, which can cause abnormalities in liver zymogram, biliary, hepatic steatosis, and changes in bile composition. However, the mechanism of these changes is still unclear, so it is not clear. Prevention and treatment methods.
3. Chemotherapy for colon cancer Clinically, the dosage and usage of chemotherapy for colon cancer should be based on individualized treatment principles.
(1) International Classic Program: It is recommended for everyone to use the classic programs in various countries and the current US colon cancer treatment guidelines.
1Mayo Clinic program:
Fluorouracil (5-FU) 425mg/m2 rapid intravenous injection, calcium leucovorin 1h, 1st to 5th day.
Calcium leucovorin (LV) 20mg/m2 static push, the first 1-5 days.
Repeat every 4 to 5 weeks.
2de Gramont program:
Calcium leucovorin 200mg/m2 was instilled for 2 hours, days 1 and 2.
Fluorouracil 400mg/m2 static push, the first day and the second day.
Fluorouracil 600mg/m2 continued intravenous infusion for 22h, days 1 and 2.
Repeat every 14 days.
3 improved de Gramont program:
Calcium leucovorin 500mg/m2 was instilled for 2 hours, days 1 and 2.
Fluorouracil 1.5 ~ 2.0g / (m2 · d) continued intravenous infusion for 48h, calcium leucovorin began 1h after the first day, 2 days.
Repeat every 14 days.
4AIO programme (German Coordination Group Programme):
Calcium leucovorin 500mg/m2 was instilled for 2 hours.
Fluorouracil 2.6g/m2 was continuously instilled for 24 hours.
Repeat every week for 6 weeks.
5FOLFOX 4 program:
Calcium leucovorin 200mg/m2 was instilled for 2 hours, days 1 and 2.
Fluorouracil 400mg/m2 static push, the first day and the second day.
Fluorouracil 600mg/m2 intravenous infusion for 22h, days 1 and 2.
Oxaliplatin (platinum oxalate, L ~ OHP) 85mg / m2 intravenous infusion for more than 2h, the first day.
Repeat every 14 days.
6FOLFOX 7 program:
Calcium leucovorin 200mg/m2 was instilled for 2 hours, days 1 and 2.
Fluorouracil 400mg/m2 static push, the first day and the second day.
Fluorouracil 600mg/m2 continued intravenous infusion for 22h, days 1 and 2.
Oxaliplatin 130mg/m2 intravenously for more than 2h, the first day.
Repeat every 14 days.
7ZFL (Saltz) program:
Calcium leucovorin 20mg/m2 static push.
Fluorouracil 500mg/m2 intravenously.
Irinotecan (CPT-11) 125mg/m2 intravenously.
Once a week, take 4 weeks for 2 weeks and 6 weeks for 1 cycle.
8FOLFIRI program:
Calcium leucovorin 200mg/m2 was instilled for 2 hours, the first day.
Fluorouracil 400mg/m2 static push, the first day.
Fluorouracil 2.4 ~ 3g / m2 continued intravenous infusion for 46h.
Irinotecan 180mg/m2 intravenously for 2h, the first day.
Repeat every 14 days.
9 capecitabine single-agent oral regimen:
Capecitabine 510mg / (m2 · d) was taken orally twice, for 14 days, stopped for 7 days, repeated every 21 days. In clinical recommendations, reduce to 3, 2 times / d, oral, take 14 days, stop for 7 days, repeat every 21 days.
10CAP L-OHP program:
Capecitabine 1000mg/m2, oral, 2 times / d, days 1 to 14.
Oxaliplatin 130mg/m2, intravenous infusion for more than 2h, the first day.
Repeat every 21 days.
Currently, Bevacizumab+Fluorouracil and Cetuximab+Irinotecan are recommended in the US treatment guidelines. Because they are not yet universally applicable, clinicians can pay close attention.
(2) Postoperative adjuvant chemotherapy: Adjuvant chemotherapy for postoperative colon cancer began in the 1950s, when nitrogen mustard and thiotepa were used as intraoperative and postoperative adjuvant chemotherapy drugs, but clinical efficacy was not obtained. For some time thereafter, colon cancer was considered to be insensitive and ineffective to chemotherapy. Until 1984, Higgins et al found that fluorouracil + MeCCNU after surgery, the 5-year survival rate of 1 to 4 positive cases of lymph nodes was significantly higher than that of the surgery alone. In 1989, Laurie et al. of the NCCTG (North Central Cancer Treatment Group) in the United States reported a randomized controlled trial of a single group of colon cancer surgery plus postoperative levamisole or fluorouracil plus levamisole adjuvant chemotherapy. The results were found in stage III (DLakes C). The disease-free survival rate of patients with colon cancer after surgery with fluorouracil and levamisole increased by 12%. In 1990, a larger group of clinical trials confirmed that fluorouracil and levamisole significantly prolonged the disease-free survival and overall survival of patients with stage III colon cancer compared with the non-chemotherapy group. A number of randomized controlled trials of approximately 4,000 patients reported thereafter confirmed that patients with stage III colon cancer received fluorouracil + leucovorin and fluorouracil + MeCCNU + VCR, and their 3-year mortality decreased by 22% and 33%, respectively. In the course of chemotherapy, the subsequent four clinical trials confirmed that 6 months of fluorouracil + leucovorin was equivalent to 12 months of fluorouracil + levamisole. The C-04 test of NSABP (National Breast and Colon Intestine Surgery Research Group) not only confirmed the above viewpoint, but also found that the addition of levamisole to fluorouracil + leucovorin did not improve the disease-free survival rate and overall survival rate of patients. The NSABP C-03 test confirmed that the fluorouracil + calcium leucovorin chemotherapy group was better than the MOF (MeCCNU, VCR, fluorouracil) chemotherapy group. The MOF regimen not only has a toxic side effect, but also has a risk of causing leukemia during the treatment. It has been replaced by a fluorouracil + leucovorin regimen in adjuvant chemotherapy for colon cancer. The NSABP C-05 trial also suggested that the addition of alpha-interferon to fluorouracil + leucovorin did not improve the survival rate of patients, and the toxicity of grade III or higher was significantly increased.
Based on the above test results, in 1997, ASCO and other literature recommended six cycles of fluorouracil + leucovorin as postoperative adjuvant chemotherapy for stage III or older colon cancer. At the same time, a comprehensive analysis of multiple randomized controlled trials concluded that elderly (>70 years old) patients can benefit from the above adjuvant chemotherapy as well as younger patients, and do not exclude them from adjuvant therapy simply because of their age.
The value of adjuvant chemotherapy for stage 2 (Dukes B or MACB2 or B3) colon cancer patients has long been controversial. In 1995, randomized controlled trials by Moertel et al. suggested that adjuvant chemotherapy had no survival advantage in patients with stage II (Dukes B2). However, several studies have concluded that adjuvant chemotherapy is still worthwhile for patients with stage II. NSABP researchers believe that adjuvant chemotherapy is equally important for the benefit of stage II and stage III patients in reducing the risk of postoperative recurrence. A meta-analysis of 1000 patients with stage II colon cancer found that adjuvant chemotherapy with fluorouracil + leucovorin was compared with surgery alone, and the 5-year disease-free survival rate increased by 2%.
Professor de Gramont of France at the 2003 ASCO conference reported the results of a well-known international randomized controlled phase III clinical trial (Mosaic trial). A total of 2246 patients with stage II and III colon cancer participated in the 12-cycle FOLFOX4 regimen and the fluorouracil/leucovorin regimen as controlled trials for postoperative adjuvant chemotherapy. Among them, 1123 cases were in FOLFOX4 and fluorouracil/leucovorin group, and 40% in group II. The results showed that the 3-year disease-free survival rate of the FOLFOX4 group was 77.8%:72.9% compared with the fluorouracil/leucovorin group, P<0.01. The FOLFOX4 regimen reduced the risk of postoperative recurrence by 23%. The 3-year disease-free survival rate of stage II patients was 86.6%:83.9% in the FOXFOX4 group compared with the fluorouracil/leucovorin group. FOL-FOX4 reduced the risk of postoperative recurrence by 31.8%. The stage III disease-free survival rate of stage III patients FOLFOX4 The group was 71.8%:65.5% compared with the fluorouracil/leucovorin group, and FOLFOX4 reduced the risk of postoperative recurrence by 24%. He believes that the FOLFOX4 regimen is safe and the first combination chemotherapy with fluorouracil/leucovorin in adjuvant chemotherapy for colon cancer. He personally believes that the 12-cycle FOLFOX4 regimen is currently the best chemotherapy regimen for colon cancer surgery.
In the case of rectal cancer, multiple randomized controlled clinical trials such as the GITSG (the Gastrointestinal Tumor Study Group) and the NSABF R-01 in the United States have shown that for the treatment of rectal cancer of stage II and III, adjuvant chemotherapy combined with chemotherapy and radiotherapy can Prolong patient-free survival and improve overall survival. In 1990, the National Cancer Institute of the United States recommended postoperative adjuvant radiotherapy and chemotherapy as the standard treatment for stage II and III rectal cancer. This principle of treatment has been extended to date, except that the chemotherapy regimen has changed with the advancement of the colon cancer protocol.
Based on the above a large amount of clinical data, in 2004, the National Comprehensive Cancet Network expert group recommended postoperative adjuvant therapy for the following colon cancer patients. T3N0M0 has high-risk factors such as tumor differentiation degree 3 to 4, lymphatic or vascular invasion, intestinal obstruction, perforation or cut-end positive, and T4N0M0 considers postoperative adjuvant therapy; T1～4N1～2M0 are treated with adjuvant therapy.
(3) Intraperitoneal chemotherapy for colon cancer:
1 basis of intraperitoneal chemotherapy: poor prognosis after colon cancer surgery has been a problem that plagues clinicians, especially in Dukes C and Dukes D colon cancer patients, the main cause of death is local and regional recurrence of the abdominal cavity and liver metastasis. Lcather et al reported that the detection rate of cancer cells in peritoneal lavage fluid after colon cancer surgery was 3% to 21%. Zybina reported that the positive rate of free cancer cells in the peritoneal cavity of rectal cancer penetrating serosa was 100%. Moreover, the effective implantation rate of free cancer cells in the abdominal cavity is 1 million times higher than that in the blood vessels or lymphatic vessels. Even if there are a small amount of free cancer cells in the abdominal cavity after surgery, the surgical area and the damaged peritoneal surface are prone to recurrence and metastasis. Foreign literature reports that abdominal recurrence within 5 years after radical resection of colon cancer, the incidence of peritoneal metastasis is 37% to 50%. Moreover, in patients with colon cancer, 20% to 40% of cases have simultaneous liver metastasis. Liver metastasis accounts for 13% to 32% of patients with postoperative recurrence and distant metastasis. The rate of liver metastasis is higher at autopsy. 50% to 80%. In order to solve the above problems, many domestic and foreign scholars have made more and more explorations on intraperitoneal chemotherapy (IPC) of colon cancer in recent years.
The main mechanisms of postoperative recurrence and metastasis of colon cancer include: A. The cancer cells that penetrate the serosal wall of the intestinal wall directly fall into the abdominal cavity. B. During the operation, proper isolation measures were not taken, and the cancer cells that fell into the intestinal lumen flowed into the abdominal cavity with the intestinal fluid through the intestinal tract. Southwick et al reported that the detection rate of cancer cells in the intestinal lumen 5 cm above and below the primary tumor was 82%, and the detection rate was as high as 10% in the intestinal lumen beyond 25 cm. C. The blood vessels in the surgical area are cut off, and the tumor thrombus in the lymphatic vessels flows into the abdominal cavity with blood and lymph. D. Tumor cell fluid reaches through the portal vein and deposits in the liver parenchyma. In addition, some small cancerous tumors that cannot be completely removed by surgery, and cancer cells wrapped in cellulose-like coagulation in the peritoneal cavity, in the case of surgery, anesthesia, etc., and the body's immunity is reduced, the cancer cells proliferate, eventually leading to local recurrence of the abdominal cavity. , metastasis and liver metastasis.
The purpose of intraperitoneal local chemotherapy is to directly increase the concentration of anticancer drugs at the tumor site, increase local cytotoxicity without increasing or even reducing or avoiding toxic side effects on the whole body. Intraperitoneal chemotherapy in the prevention and treatment of local recurrence and liver metastasis of colon cancer has the following advantages: A. Intra-abdominal chemotherapy has the characteristics of highly selective regional chemotherapy, which can directly soak free cancer cells in the abdominal cavity and residual microscopic cancers after surgery. The high concentration of anticancer drug solution increases the killing ability of anticancer drugs against tumor cells. After high-dose intraperitoneal administration of certain anticancer drugs, the intraperitoneal drug concentration is much higher than the blood concentration, and the intraperitoneal concentration is several hundred times of the plasma concentration after several hours of administration. B. Anticancer drugs are absorbed into the liver through the portal vein, which can provide a constant and persistent high concentration of anticancer drugs in the portal vein blood and liver, so that cancer cells metastasized to the liver are attacked by high concentrations of anticancer drugs. C. Most anticancer drugs are absorbed into the liver through the portal vein. First, they are metabolized by the liver. Only a very small amount of drugs enter the systemic circulation, which can reduce the systemic toxicity and produce maximum drug dose tolerance.
In addition, on the basis of intraperitoneal chemotherapy, tumor tissue cells were found to be sensitive to heat and have different temperature tolerance to normal tissue cells. The blood vessels in the tumor tissue lack smooth muscle and cannot expand with the increase of temperature. When the temperature is increased, the blood flow in the tumor can be reduced more, which can cause the environmental changes in the tumor tissue, hypoxia, pH value, nutrient deficiency, and affect the tumor cells. Proliferation and synthesis of DNA and RNA, thereby damaging tumor tissue cells. Studies have shown that normal tissues can tolerate 47 ° C for 1 h under high temperature conditions, while malignant tumor cells can only tolerate 43 ° C for 1 h. Anticancer drugs have synergistic effects with hyperthermia, and heat promotes the binding of chemotherapeutic drugs to cancer target cells and enhances their activity. Moreover, heat can change the membrane permeability of cancer cells, which is beneficial to the infiltration of some chemotherapeutic drugs into cells and enhance the effect. Heat can also increase the DNA cross-linking of certain anticancer drugs and cancer cells, enhance the killing effect on cancer cells and simultaneously inhibit the repair of tumor cells after chemotherapy. In vitro tests showed that anti-cancer effects of cyclophosphamide (CTX), mitomycin (MMC), cisplatin (DDP), and fluorouracil (5-FU) were significantly enhanced under warming conditions. In addition, peritoneal continuous hyperthermic perfusion chemotherapy can also remove residual cancer cells in the abdominal cavity by mechanical scour. Therefore, many researchers are also exploring the role of continuous hyperthmic peritoneal perfusion chemotherapy (CHP-PC) in order to further improve the treatment of colon cancer and reduce the recurrence and metastasis of colon cancer.
2 solvent, capacity and drug selection for intraperitoneal chemotherapy: intraperitoneal chemotherapy solution mainly consists of solvent and anticancer drug. The solvent is usually physiological saline, Ringer's solution or 1.5% Inpersol solution. It is also useful to report on heavy distilled water. Inpersol solution is a hypertonic liquid containing 1.5% glucose. Its osmotic pressure is balanced with the hydrostatic pressure of the abdominal cavity. It is originally used for peritoneal dialysis in patients with renal failure to prevent peritoneal overabsorption, but it is not conducive to anticancer due to high osmotic pressure. The drug is dispersed into the tumor tissue. Due to the low osmotic pressure of saline or Ringer's solution, anticancer drugs easily enter the tumor tissue, improve cytotoxicity and enhance anticancer effect. According to the study of peritoneal fluid dynamics, it is only when a large amount of liquid is infused to achieve abdominal cavity expansion to ensure that the abdominal organs and the entire peritoneal surface are in contact with the anticancer drug liquid. Rosensheir et al. injected a radiotracer into the peritoneal perfusate to study the peritoneal fluid dynamics. At least 2000 ml of liquid must be perfused to overcome the free flow resistance of the peritoneal fluid, ensuring uniform distribution of fluid in the abdominal cavity.
The choice of anticancer drugs depends on the drug must be able to kill colon cancer cells by itself or its metabolites; the drug must have low peritoneal permeability; the drug must be quickly cleared from the plasma; the drug must have a strong penetrating tumor tissue ability. According to the above principles, the most commonly used anticancer drugs for intra-abdominal chemotherapy for colon cancer are fluorouracil, mitomycin (MMC) and hydroxycamptothecin (HCPT). Some people use some biological agents such as interferon, interleukin (interleukin 2) and monoclonal antibodies in intraperitoneal chemotherapy according to the characteristics of clearing the macromolecular substances in the abdominal cavity than the small molecules to enhance the anticancer therapeutic effect.
Indications for intraperitoneal chemotherapy: Indications for intra-abdominal chemotherapy for colon cancer are radical surgery in patients with advanced colon cancer invading the serosa; Dukes C-stage colon cancer; scattered microscopic metastatic nodules in the peritoneum, can only be removed A palliative operation of the primary tumor; after surgery, abdominal recurrence and liver metastasis can not be re-operation or reoperation; extensive abdominal cancer metastases or large-volume malignant tumors invading the surrounding organs can only perform palliative cell debulking; colon Cancer with malignant ascites.
There are distant metastases such as lungs, brain and bones, severe cardiovascular diseases and liver and kidney dysfunction, and are not suitable for intraperitoneal chemotherapy. In addition, because of the limited penetration of anti-tumor drugs, intraperitoneal chemotherapy is effective for small and medium-sized peritoneal metastasis, but poor for metastatic adenocarcinoma of more than 5 cm.
4 intraperitoneal chemotherapy:
A. Preoperative chemotherapy: induced intraperitoneal chemotherapy (IIPC), commonly used in patients with postoperative abdominal recurrence and metastasis of colon cancer. On the first day of treatment, mitomycin (MMC) 12mg/m2, 2-4 days, fluorouracil 20mg/(kg·d) intraperitoneal chemotherapy, 5 days for 1 course of treatment. Another option is fluorouracil 20mg / (kg · d) for 5 days for intraperitoneal chemotherapy, the third day with mitomycin 10mg / m2, intravenous infusion, the same 5 days for a course of treatment. After the IIPC, the volume of the tumor in the abdominal cavity can be reduced, which is conducive to the complete removal of the abdominal tumor.
B. Intraoperative chemotherapy: intraperitoneal hyperthermic perfusion chemotherapy (CHPPC), the device consists of a heated water incubator, a heat exchanger, an adjustable speed (flow) perfusion pump, an electronic temperature sensor and a thermofusion catheter system. Guangzhou Nanfang Hospital and National University of Defense Technology jointly developed the NK-1 single-computer computerized thermo-infusion chemotherapy machine, which uses the measurement and control function of the computer microprocessor to automatically adjust and control the pumping and perfusion system for heating, constant temperature, temperature measurement and liquid medicine. The chemotherapeutic solution is poured into and discharged into the abdominal cavity at a constant temperature, constant speed, and constant amount according to the required requirements.
Specific method: After the tumor was removed under general anesthesia, a silicone catheter with an inner diameter of 0.8 cm and an outer diameter of 1 cm was placed in the pelvic cavity and the left and right upper abdomen, respectively, and the cuffs were taken out from the abdominal wall, and then the incision was closed by suturing. Upper abdominal catheter. The pelvic catheter was filled with 2000 ml of heated chemotherapeutic fluid, and then the left and right upper abdominal catheter drainage was opened, and the temperature probe was placed at the input end and the drainage tube to monitor the temperature and temperature.
According to whether the chemotherapeutic fluid is circulated and infused into circulatory peritoneal hyperthermic perfusion chemotherapy and non-circulating intraperitoneal hyperthermic perfusion chemotherapy The former is to re-circulate the chemotherapeutic fluid that is drained into the abdominal cavity, and the chemotherapeutic fluid that is drained from the latter is no longer used. According to whether to increase the internal volume of the abdominal cavity, it is divided into simple peritoneal hyperthermia and peritoneal cavity expander (PCE). The main purpose of the latter is to increase the area of contact between the abdominal organs and the peritoneum and the chemotherapy liquid phase. The chemotherapeutic solution is evenly distributed in the abdominal cavity, avoiding the uneven distribution of the peritoneal hyperthermic chemotherapeutic solution in the abdominal cavity, and the ineffective cavity which is not in contact with the chemotherapeutic solution, thereby fully exerting the thermochemotherapy effect.
C. Postoperative chemotherapy: a. Tenckhoff catheter system: under local anesthesia or intraoperatively, the catheter is placed in the abdominal cavity by the rectus abdominis in the umbilical plane, the distal end is placed in the abdominal cavity, and the proximal end is subcutaneously made by the sneak tunnel from the left. Or the right lower abdomen was taken out and fixed, and the chemotherapeutic fluid was injected into the abdominal cavity through the Tenckhoff catheter. b. Port-A-Cath Catheter System: The catheter system consists of a conical stainless steel housing with a silicone diaphragm closed outer injection valve connected to the Tenckhoff catheter system. The Tenckhoff catheter was placed under operation or under local anesthesia, the injection valve was buried under the skin, and the proximal end of the Tenckhoff catheter was connected to the hypodermic injection valve through a subcutaneous tunnel. During chemotherapy, the skin of the subcutaneous valve is disinfected first, and the port-A-Cath needle is inserted through a hypodermic injection valve. The anticancer drug can be infused or injected into the abdominal cavity with a syringe. c. Percutaneous transluminal catheterization chemotherapy: Clinically, deep venous catheters are used for intraperitoneal catheterization chemotherapy. METHODS: The 16Ga and 1.7mm deep venous puncture tubes produced by Arrow Company of the United States were used to disinfect the abdominal puncture site. Under local anesthesia, the abdominal puncture was performed. After the abdominal cavity was confirmed, the catheter wire was inserted from the tail, the catheter was placed along the guide wire, and then the catheter was inserted. The guide wire is dropped into the chemotherapy drug and the solvent through the catheter, and the catheter can be left until the end of the treatment. This method is simple, safe and reliable.
5 Clinical effect of intraperitoneal chemotherapy: Sugarbaker et al performed inductive intraperitoneal chemotherapy for 26 patients with colon cancer and appendix adenocarcinoma with peritoneal metastasis, 5 patients with abdomen metastatic adenocarcinoma less than 5 mm in diameter, and 4 patients with complete remission after IIPC, 1 Partial relief, the surgical help rate was 100%; 7 patients with 5mm ~ 5cm were partially relieved, the surgical help rate was 100%; and among the 15 patients greater than 5cm, 8 cases were partially relieved, and the surgical help rate was zero. It can be seen that IIPC is effective for small and medium-sized peritoneal metastatic adenocarcinoma, but has a poor effect on large-volume peritoneal metastatic adenocarcinoma. Many foreign authors have a positive opinion on intraperitoneal chemotherapy for diffuse metastatic carcinoma of the abdomen. In the adjuvant chemotherapy of colon cancer, many foreign authors compared intraperitoneal chemotherapy with intravenous chemotherapy or intravenous chemotherapy alone, compared with intraperitoneal chemotherapy and simple intravenous chemotherapy, the first, third, and fifth-year survival rates were better than intravenous chemotherapy alone. However, many Japanese authors have a negative attitude in recent articles. This aspect is worth exploring.
6 complications of intraperitoneal chemotherapy: drugs for intraperitoneal chemotherapy can have complications, divided into acute and chronic. A. Acute complications: digestive tract reaction, myelosuppression, decreased organ function, chemical peritonitis, etc. B. Chronic complications: mainly intestinal adhesions, intestinal obstruction, chronic abdominal pain, etc. Sometimes chronic complications are not easily distinguished from surgery and tumor recurrence. The incidence of acute complications is related to the type of drug selected, its dose, and the concentration of chemotherapeutic fluid. C. Intra-abdominal tube complications: intestinal perforation, hemorrhage, intestinal obstruction, catheter blockage, infection and abdominal pain. The most common is catheter blockage. Sugarbaker was equal to the complication of 39 patients with gastrointestinal tumors who underwent early postoperative chemotherapy in 1989. Two patients died (intestinal perforation and pulmonary infection, respectively). D. Other complications: intestinal perforation, leukopenia, pancreatic fistula, persistent intestinal paralysis, nausea, primary peritonitis, etc. There are also reports of extensive peritoneal adhesions. In addition to myelosuppression, liver and kidney dysfunction, and chemical peritonitis, intestinal obstruction, intestinal adhesions, and more serious side effects are rare. As technology matures and progresses, strict adherence to operational practices, abdominal chemotherapy is a safe treatment.
4. Interventional radiology of colon cancer Interventional radiology was first proposed by the American radiologist Margulis, in which the needle or catheter was inserted into the human lesion area under imaging guidance. , histology, biochemistry, bacteriology diagnosis and treatment techniques. Interventional therapy for colon cancer is a method of comprehensive treatment. Especially in cases where surgery is not possible, interventional therapy combined with other methods can improve the efficacy. Interventional treatments for colon cancer include transarterial infusion chemotherapy, selective arterial embolization, direct tumor puncture, and lymphatic infusion chemotherapy. Here we focus on arterial intubation chemotherapy for colon cancer.
Intra-arterial infusion chemotherapy for colon cancer began in the 1960s. Miura et al concluded that 220 cases of colon cancer were treated with arterial infusion chemotherapy and found that the curative effect was significantly better than systemic chemotherapy. For patients with advanced surgery who could not be surgically removed, the average survival time of arterial intubation chemotherapy was 11.6 months, and the 1-year survival rate was 39%. Combined with arterial chemotherapy and radiotherapy, the 1-year survival rate could be increased to 58% to 63%. From 1989 to 1991, the Chinese Academy of Medical Sciences Cancer Hospital used transfemoral intubation to the inferior mesenteric artery or superior rectal artery infusion chemotherapy in 25 patients with advanced rectal cancer. After treatment, 81% of patients had improved bloody and diarrhea symptoms, and 52% of tumors shrank. Recently, comprehensive treatment measures based on arterial intubation chemotherapy have played an increasingly important role in the treatment of colon cancer.
(1) indications and contraindications: inoperable patients with advanced colon cancer, can also be combined with radiotherapy, hyperthermia, cryotherapy to improve efficacy and prolong survival; before and after colon cancer surgery, to reduce surgical bleeding and reduce resection Scope, improve surgical resection rate, prevent recurrence and improve the effect of surgical treatment, using arterial intubation chemotherapy for induction chemotherapy and intensive treatment; patients with liver metastasis from colon cancer or patients with postoperative liver metastasis are well treated with arterial infusion .
Not suitable for arterial intubation and angiography, the general situation is poor, there are infected, heart, liver and kidney function disorders are not suitable for arterial intubation chemotherapy. In patients with early colon cancer, surgery can be completely removed, and generally no arterial intubation chemotherapy is required.
(2) Selection of chemotherapeutic drugs: Colon cancer is less sensitive to chemotherapeutic drugs, and many chemotherapeutic drugs have lower curative effect on colon cancer. Commonly used drugs for the treatment of colon cancer are fluorouracil, mitomycin, HCPT, L-OHP, irinotecan (CPT-11), etc. Currently, fluorouracil is still the drug of choice for the treatment of colon cancer. L-OHP and irinotecan are widely used in the treatment of colon cancer in recent years, and are also effective in patients with fluorouracil resistance. The usual dose of chemotherapy drugs is 5-FU 0.5～1g, mitomycin 20～40mg, HCPT 40mg, irinotecan 500mg. Colon cancer artery catheterization chemotherapy is recommended, and 2 to 3 combinations of the above drugs can be used.
(3) Method:
1 patient preparation: general angiographic preparation such as iodine allergy test, surgical area disinfection. Preoperative lesion imaging was qualitatively located, the extent of the lesion was determined, and selective intubation was guided.
2 device preparation: surgical package for angiography, vascular sheath, Cobra, Simmon or single curved visceral artery catheter of 5.0 ~ 6.0 F. If you want to superselect the intubation, you must also prepare special catheter, such as the coaxial infusion catheter 3.0 F Tracker or SDS coaxial perfusion guide wire and so on.
3 arterial perfusion technique:
A. Non-selective arterial perfusion: only the catheter is inserted into the abdominal aorta. If the tumor is in the ascending or transverse colon, the catheter is placed at the level of the diaphragm. Generally, the position of the catheter head is in the thoracic vertebra of the 9th to 11th, and the medicine can also smoothly enter the celiac artery, and it is also effective for liver metastasis. If the tumor is in the descending colon or sigmoid colon, the catheter head is at the level of the 2nd to 3rd lumbar vertebrae, allowing the drug to enter the inferior mesenteric artery and the internal iliac artery. Non-selective perfusion is indicated for patients with severe localized infiltration and adhesion of the tumor and extensive lymph node metastasis. The advantage is that the intubation is easy, and the intestinal tissue erosion and rupture caused by the excessive concentration of the drug in the intestinal tissue can be avoided.
B. Superselective arterial infusion: According to the location of the tumor, the Cobra or single curved catheter is used to select the superior mesenteric or inferior angiography to understand the tumor supply artery, and then the catheter is fed into the coaxial catheter or the coaxial guide wire with the end hole. Further tumor vascular superselective intubation. The cecal cancer is over-selected to the ileal artery, the colon cancer is over-selected to the right colon, the transverse colon cancer is over-selected, the colonic artery is over-selected, the left colon is sigmoid, and the upper rectal cancer is selected from the superior rectal artery. The bilateral internal iliac artery or superior iliac artery was chosen. Because of the variation of arterial cancer and the number of anastomotic branches in the colon cancer, the superselective intubation is mainly based on the tumor supplying artery indicated by angiography, and it is not necessary to mechanically dissect the normal anatomical vessels.
(4) Auxiliary measures:
1 anti-inflammatory: the use of hormones to prevent chemotherapy-induced drug stimulation caused by excessive intestinal inflammatory response.
2 antiemetic: non-superselective intubation has a more serious gastrointestinal drug response. An antiemetic agent such as granisetron can be selected.
3 pain relief: rectal cancer arterial catheterization chemotherapy contrast agent into the hip muscles and skin blood vessels, can cause severe pain. In order to prevent pain, intravascular anesthesia can be used to infuse 0.5% procaine 3 to 4 ml or 2% lidocaine 3 to 4 ml via a catheter, and then inject a contrast agent and a perfusion chemotherapy drug to relieve pain. It is recommended to use 10ml of dexamethasone in the blood vessels to improve the analgesic effect. If you switch to a non-ionic contrast agent, you can tolerate it without an analgesic.
4 anticoagulation: heparinization, superselective intubation to block blood flow is easy to thrombosis, intermittent injection of heparin saline through the catheter.
(5) Complication prevention and treatment:
1 partial hematoma: mostly due to insufficient puncture point compression to stop bleeding, also seen in the puncture device is too thick, repeated replacement of the catheter without the use of vascular sheath, high blood pressure are more likely to occur. The prevention method is to effectively compress the blood vessel puncture point to stop bleeding after the catheter is pulled out, instead of only pressing the skin puncture point, the anticoagulant heparin is used as little as possible during operation to ensure normal blood pressure. Treatment is mainly local physiotherapy to improve symptoms, accelerate hematoma absorption, prevent infection, huge hematoma or severe comorbidities to draw suction or surgical resection.
2 thrombosis: platelet deposition after the damage of the blood vessel wall can form a thrombus, the guide wire and catheter placement time is too long, the formation of surface clots can also cause thrombosis. Treatment: lightly observe the anticoagulation and vasodilator treatment, severe cases such as life-threatening, organ function or limb necrosis, rapid interventional methods should be used for percutaneous, transluminal, transcatheter perfusion of urokinase thrombolysis Treatment or surgical removal of the embolus.
3 vascular rupture: caused by the rough operation of the insertion catheter or excessive force of the superselective guide wire. Only the guide wire penetrates the blood vessel, the catheter is reserved, and the close observation can stop itself. If the bleeding cannot be stopped for a long time, the transcatheter can be occluded with absorbent gelatin sponge particles or stainless steel.
4 intestinal perforation: excessive use of chemotherapy drugs or thrombosis. Superselective arterial infusion should reduce the amount of drug and heparinization to avoid thrombosis. Once the intestinal perforation is formed, an urgent surgical treatment is required.
5 Muscle or subcutaneous vascular injury occlusion: The key is prevention. If there is a burning pain in the muscle and skin area during angiography, it means that the blood vessels are stimulated here, and the intubation should be selected or superselected to avoid the muscle or skin blood vessel branch to avoid the contrast agent. And enter into anticancer drugs. Otherwise, the entry of contrast agents and anticancer drugs will cause endovascular inflammation and even vascular occlusion, resulting in local skin muscle ischemia and necrosis. Once the operation occurs, it should be active anti-inflammatory (using hormones), dilate blood vessels and improve blood circulation, and local physiotherapy.
5. Biological therapy
(1) Non-specific immunotherapy: Non-specific immunotherapy refers to non-specifically improving the overall immunity of the body by injecting immunostimulatory factors, cytokines or activated immune cells into the body to achieve the purpose of killing tumor cells. This immunotherapy method does not depend on the body's own immune status, and is therefore suitable for tumor patients with low autoimmune.
1 non-specific stimulating factor: through the application of immunostimulating stimulating factors, stimulate the body's immune system, enhance the body's non-specific anti-tumor immune response, and achieve the purpose of killing tumor cells. Clinical studies have found that stimulating factors combined with other anti-tumor therapies may improve the efficacy of killing tumor cells.
A. Levamisole: a synthetic phenyliminothiazole. In 1974, Verhaegen took the lead in the treatment of Dukes A, B, and C colon cancer patients with levamisole. The 5-year survival rate was 69% in the treatment group, which was significantly higher than 37% in the control group. In 1989, NCCTG and Mayo Hospital reported the results of a combination of levamisole and levamisole in combination with fluorouracil in the treatment of colon cancer patients. Long-term follow-up of 401 patients (median over 7 years of observation) was performed. The results showed that the combination of levamisole and fluorouracil did not improve overall survival compared with levamisole alone, but significantly reduced tumor recurrence. A subsequent study included 1296 patients with colon cancer (including 929 patients with Dukes C). The results showed that levamisole was not effective in patients with Dukes C stage colon cancer; levamisole combined with fluorouracil significantly reduced tumor recurrence rate. And extend the 3-year survival rate. A median of 5 years of follow-up showed that the combination of the two drugs reduced the case fatality rate by one-third. This is one of the most exciting examples of current tumor immunotherapy. In 1989, NCI proposed levamisole and fluorouracil as adjuvant therapy for Dukes C stage colon cancer. Currently, this method has become the standard adjuvant treatment for postoperative colon cancer surgery.
B. Freeze-dried BCG (BCG): It is an attenuated strain of Mycobacterium tuberculosis. It was originally a vaccine against tuberculosis. It was found to have a certain effect of improving non-specific immunity and antagonizing tumors. The exact mechanism of anti-tumor effect of lyophilized BCG (BCG) is still unknown, suggesting that it may promote the activity of antigen-presenting cells and enhance the T-lymphocyte-mediated cellular immune response.
Freeze-dried BCG (BCG) has been used alone in the treatment of various malignant tumors such as leukemia and lung cancer, but it has been proven to be unsatisfactory. Malignant tumors currently treated with lyophilized BCG alone are limited to melanoma and bladder cancer, and are more commonly used as immunoadjuvants for active specific immunotherapy of tumors. Clinical studies have found that when using a tumor vaccine such as colon cancer, lyophilized BCG (BCG) can be used as an immunological adjuvant to achieve exciting results. The most common adverse reaction with lyophilized BCG (BCG) is flu-like symptoms, which usually disappear within 36 hours. A small number of patients have complete cytopenia, leukopenia, thrombocytopenia, and abnormal liver function.
2 Cytokines: Cytokines have a wide range of biological effects and are involved in the regulation of the development and progression of many physiological and pathological processes in the body. Some cytokines have the ability to directly and indirectly kill tumor cells. The anti-tumor mechanism of cytokines is: up-regulating the expression and secretion of surface molecules and receptors of immune cells; enhancing the immune surveillance function of the body, promoting the proliferation and differentiation of T lymphocytes and the maturation of cytotoxic T cells, stimulating the production of B lymphocytes Antibodies, increase the activity of NK cells, stimulate anti-tumor immune responses such as macrophages; promote the expression of MHC molecules in tumor cells, enhance the immunogenicity of tumor cells and sensitivity to immune effector cells; some cytokines directly destroy tumor cells And promote its role in the occurrence of apoptosis.
A. Interferon (IFN): is a group of proteins produced by cells infected with or infected with antigen, and can be divided into α, β and γ 3 types. Among them, IFN-α and β are produced by virus-infected cells, and IFN-γ is mainly produced by antigenic stimulation. In addition to T cells, NK cells and LAK cells also produce IFN. In addition to antiviral, the biological effects of interferon also have activities such as immune regulation, interference with cell proliferation, inhibition of angiogenesis, regulation of differentiation, and promotion of expression of various cell surface antigens. When used in tumor therapy, interferon can directly inhibit the growth of tumor cells, and on the other hand, it can indirectly kill tumor cells by activating NK cells and macrophages, and inducing MHC antigens in tumor cells.
In the past, clinical interferon was mainly used for the treatment of non-solid tumors such as leukemia and lymphoma. In recent years, clinical studies abroad have shown that in the chemotherapy of colorectal tumors (especially cisplatin-based chemotherapy), if combined with IFN-α or adiponectin (IL-2) and other biological immunotherapy, Can significantly improve the treatment effect.
B. Aldileukin: In humans, interleukin-2 (IL-2) is mainly produced by CD4 cells. IL-1 produced by antigen-presenting cells is a necessary condition for inducing secretion of IL-2 by T cells. The ability of T cells to secrete IL-2 is closely related to the immune function of the body. In cancer patients, especially in advanced tumor patients, the ability of peripheral blood T cells to secrete IL-2 is significantly lower than that of normal people. After surgical removal of the primary tumor, the patient's secretion capacity can return to normal. IL-2 has a variety of biological activities: a. It can activate T cells with IL-2 receptor expression, but quiescent T cells cannot be activated because they have no IL-2 receptor expression. In vitro, IL-2 promotes the proliferation of Th, Ts and CTL. High doses of IL-2 also enable the proliferation of T cells in vivo. b. Enhance the killing activity of NK cells and macrophages on microorganisms and tumor cells. C. Promote B cell proliferation and differentiation. D. Inducing T cells to secrete cytokines such as IFN-γ, TNF-α, and colony-stimulating factor (2qF). e. Induction of LAK killer cell formation in vitro.
In 1992, the US FDA first approved the use of aldileukin (IL-2) in the treatment of advanced renal cell carcinoma. Later, interleukin (IL-2) was gradually applied to other malignant tumors such as colon cancer. In the current biologic treatment of colorectal tumors, either aldileukin (IL-2) or interleukin (IL-2) can be used in combination with LAK cells or TIL cells to enhance immunity of the latter two. treatment effect.
C. Tumor Necrosis Factor (TNF): Carswell first isolated and identified tumor necrosis factor in 1985 and found it has a surprising inhibitory effect on animal tumors. In humans, TNF-α is mainly produced by monocytes and macrophages, and T cells can also secrete TNF-α. The biological activities of TNF-α mainly include: a. activation of various immune cells, can enhance NK cell activity, activate and induce macrophage tumoricidal activity, stimulate T cell activation and proliferation; b. enhance vascular endothelial cell passage Permeability, induces the expression of accessory molecules in vascular endothelial cells; c. promotes the expression of MHC-I and MHC-II molecules on the cell surface; d. induces the production of proteins in the acute phase.
Although Carswell et al. initially found that TNF-α has a strong anti-tumor effect in mouse experiments, it did not achieve significant therapeutic effects in subsequent Phase I and Phase II clinical trials. Since TNF-α can induce serious adverse reactions in the human body, it limits the use of effective doses in clinical trials, which may be an important reason why clinical trials have not achieved satisfactory results.
3 lymphokine activated killer cell (LAK): human peripheral blood lymphocytes are cultured in vitro, induced by high concentration of cytokines (mainly IL-2), resulting in a class of non-specific killing Effector cells of tumor cells. LAK cells are mainly derived from peripheral blood lymphocytes, and their phenotypes are either CD3 or CD3-, often with NK cell-like markers (CDL6 and CD56). Its killing tumor cells do not require antigen sensitization and no MHC binding. Therefore, the precursor cells of LAK cells are considered to be NK cells, but unlike NK cells, their growth and effector functions are dependent on IL-2.
In 1984, Rosenberg first applied LAK to clinical studies, demonstrating that LAK therapy can shrink or resolve tumors in a subset of patients with renal cell carcinoma, melanoma, and colon cancer. Recently, clinical trials have shown that the application of LAK cells alone is not effective, but if combined with high-dose interleukin (IL-2), it can effectively maintain the activity of LAK cells, enhance the immune function of the body, and improve the effect of inhibiting tumors.
(2) Specific immunotherapy: Specific immunotherapy refers to inducing the body itself to produce immunity against a certain tumor antigen by injecting a tumor vaccine, a monoclonal antibody antagonist or an immunologically active cell (such as a TIL cell) into the body. The immunotherapy method has the advantages of being tumor-specific, highly targeted, capable of individualized treatment, and immunological memory.
1 tumor vaccine: tumor vaccine includes inactivated autologous tumor cells, extracted tumor antigens and synthetic tumor peptide antigens. By vaccinating patients, the patient's body is stimulated to produce a specific immune response against tumor cells, killing tumor cells without Damage to normal cells around. Tumor vaccine can also induce immune memory cells, produce long-term immune effects, prevent tumor metastasis and recurrence, and is an ideal immunotherapy method.
After entering the 21st century, researchers have made a lot of attempts to develop and apply tumor-specific vaccines. At present, a variety of vaccines have been put into clinical use. Hoover et al. conducted a clinical trial of autologous tumor vaccine plus freeze-dried BCG (BCG) in patients with advanced colon cancer. The results showed that the 5-year survival rate of patients increased by 31%, and the local recurrence rate decreased by 50%.
However, the immunogenicity of tumor vaccines is weak, which may lead to immune tolerance. Therefore, some large clinical centers in foreign countries have carried out clinical trials of dendritic cell tumor vaccines, that is, tumor antigens or tumor cell extracts are loaded on dendritic cells to make dendritic cell tumor vaccines, and then return to tumor patients. It can effectively activate the body's anti-tumor immune response and produce tumor antigen-specific cytotoxic T cells. Initially used for experimental treatment of melanoma, kidney cancer and colon cancer, the results show that the clinical effect is good, no significant side effects, but long-term efficacy needs further verification.
2 anti-idiotype antibodies: according to the principle of idiotype-anti-idiotype network, immunize animals with human tumor antigen antibody (primary antibody), the unique determinant of antibody can be used as an antigenic epitope to stimulate the animal body to produce anti-idiotypic antibodies ( The secondary antibody has a structure similar to that of a tumor antigen and can be used as an internal image of a tumor antigen for immunization. The organism thus produces the corresponding antibody (tri-antibody), which has the ability to specifically recognize tumor antigens, or effector cells in the mediator to kill target cells.
In layman's terms, anti-idiotypic antibodies are endogenous tumor antigens. The anti-idiotype antibody tumor vaccine prepared by this method is easy to obtain, safe and reliable, and has higher specificity than the traditional tumor antigen vaccine. Thereby, the problems of the source of tumor antigen and the cross reaction between certain antigenic determinants on the tumor antigen protein and normal cells are overcome. Clinically, it has been used to treat solid tumors such as hematological malignancies and colon cancer, and has achieved good results.
3 Tumor-infiltration lymphocytes (TIL): a type of cells that infiltrate into solid tumors and surrounding lymph nodes, which are often sensitized by tumor antigens and have specific anti-tumor effects. TIL is also a group of heterogeneous cells, mainly composed of T lymphocytes, followed by NK cells and B lymphocytes. TIL was first reported by Rosenberg and used in the clinic. It is usually isolated from surgically removed tumor masses and lymph nodes, and can also be obtained from the patient's thoracic and abdominal exudate. The isolated cells can be cultured and expanded in vitro under the stimulation of aldileukin (IL-2). During the amplification process, the mixed tumor cells in the immune cells are killed by LAK or cytotoxic T cells (CTL).
The killing effect of TIL on tumor cells may be achieved by CD4 and CD8 effector T cells, which have specific lysis effects on tumor cells. In addition, TIL can also release immune effector molecules to kill tumor cells. Immune effector molecules can be divided into two categories, one is cytokines, such as IL-6, TNF-α and IFN-γ, which can kill tumor cells directly or by activating cytotoxic cells; the other is cytotoxic enzymes. For example, perforin and cytolysin can destroy the tumor cell membrane, reduce intracellular osmotic pressure, and swell and die.
At present, TIL is mainly used for the treatment of advanced liver cancer, melanoma and colon cancer. It is usually combined with leuprosin (IL-2) to improve the efficacy. Some scholars also advocate the combination of cytokines such as TNF-α and IFN-α. Recently, clinical studies have shown that TIL cells have better proliferative activity and specificity for tumor killing than LAK cells.
4 Antibody-directed therapy: Monoclonal antibody refers to the fusion of myeloma cells and activated B lymphocytes, and the obtained progeny hybrid cells inherit the characteristics of two parents, namely the immortalization of malignant tumors and the ability of B lymphocytes to produce antibodies. A variety of monoclonal antibodies against tumor antigens can be prepared using this hybridoma technique.
In order to increase the ability of monoclonal antibodies to kill tumor cells in vivo, a variety of immunoconjugates have been used in the preparation. That is, using an antibody as a carrier, an effector molecule (such as a cytotoxin, a chemotherapeutic drug or a radionuclide) is a warhead, and the two are coupled, and depending on the specificity of the antibody, the effector molecule is delivered to the tumor site to selectively kill the tumor cell; Genetic engineering techniques can also be used to prepare human monoclonal antibody or chimeric antibody (ie, murine Fab segment and human Fc segment), overcome the heterogeneity of antibodies, enhance the binding ability of antibodies to immunocompetent cells, and achieve effective killing. The purpose of tumor cells. Depending on the coupling effector molecule, monoclonal antibody-directed therapies are mainly:
A. Monoclonal antibody and cytotoxin coupling: Currently the most widely used protein synthesis inhibitory toxins, such as ricin, diphtheria toxin and Pseudomonas aeruginosa exotoxin. The purpose of immunotoxin therapy is to eliminate metastases, especially small metastases. An ideal immunotoxin should kill all cancer cells at high concentrations without damaging normal cells. In addition to the specificity and activity of the antibody, this also depends on the ability of the immunotoxin to contact cancer cells and penetrate cancer cells. There is currently no immunotoxin with ideal specificity, half-life and penetration.
B. Coupling of monoclonal antibodies with chemotherapeutic drugs: Studies have shown that monotherapy-conjugated chemotherapeutic drugs are generally stable and have almost no adverse effects on the human body. However, studies have also found that the activity of the monoclonal antibody and the chemotherapeutic drug after the coupling is reduced. At present, its clinical application reports are still rare, mainly used for colon cancer and lung cancer, but they have not achieved obvious effects.
C. Monoclonal antibody binding to nuclide: The advantage of this method is that the nuclide is easy to be coupled with the antibody, easy to trace, to determine its distribution and half-life in vivo; to enable surrounding tumor cells to be irradiated, so that even part of the tumor cells Does not express antigen, can not bind to monoclonal antibody, can still be killed by radionuclide rays. This method has been applied to the treatment of colon cancer, lymphoma and leukemia.
(3) Tumor gene therapy: using physical and chemical methods or virus-mediated DNA transfer technology, replacing or supplementing defective genes with functionally normal genes, or transferring new genes into target cells to safely and effectively inhibit The role of tumors, to achieve the purpose of treating tumors.
1 basic concept:
A. Gene replacement: refers to the replacement of the disease-causing gene into a normal gene, so that the disease-causing gene is permanently corrected.
B. Gene correction: refers to the correction of the mutated base sequence of the gene, while the normal part is retained.
C. Gene augmentation: refers to the introduction of a gene of interest into a diseased cell or other cell, and the expression product of the gene of interest modifies the function of the defective cell or enhances the original function.
D. Gene inactivalion: refers to the use of antisense nucleotides or ribozymes to specifically block the expression of certain genes. E. Ex vivo gene therapy: refers to the introduction of a vector containing a foreign gene into an autologous or allogeneic cell in vitro, and the modified cell is expanded in vitro and then returned to the patient. F. In vivo Gene therapy: refers to the direct introduction of the gene of interest into a human body through a viral vector, allowing it to enter the target organ and fully express it.
2 gene therapy methods:
A. Inhibition of oncogene expression: a. In the development of most tumors such as colon cancer, activation and overexpression of various oncogenes and related genes are involved. These genes not only provide markers of cancer cells, but also serve as targets for gene therapy. Inhibition of the expression of these genes will likely result in a reversal of the cancer cell phenotype. This gene therapy strategy includes:
Antisense oligonucleotides are those in which a nucleotide fragment complementary to an oncogene is introduced into a cancer cell to block the translation of the oncogene, thereby blocking the expression of the oncogene; ribozyme is An enzyme-catalyzed RNA molecule, which is designed to be complementary to a specific oncogene mRNA and then introduced into cancer cells, which can bind to oncogene mRNA and cut off oncogene mRNA, thereby blocking cancer. Gene expression.
b. Tumor suppressor gene is a kind of important gene related to tumorigenesis. It normally has the function of inhibiting excessive proliferation and dedifferentiation of cells. Mutation or dysfunction of tumor suppressor genes is an important factor related to tumorigenesis, development, metastasis and prognosis. By introducing wild-type tumor suppressor genes (such as p53 and RB) into cancer cells to replace the tumor suppressor genes deleted or mutated in tumor cells, and restore the normal function of tumor suppressor genes, it can partially reverse the malignant tumors of colon cancer and other malignant tumors. Type, thereby improving the therapeutic effect of the tumor.
B. Enhancing the activity of anti-tumor drugs: introducing a prodrug converting enzyme gene or a drug-sensitive gene into a tumor cell, thereby enhancing the killing of the tumor cell by the drug or increasing the sensitivity of the tumor cell to the drug, and enhancing the anti-tumor effect, and the therapy is further Called "suicide gene therapy." As an example of a currently popular treatment, the researchers injected a cell line that produces retroviral particles into tumor cells. Because the virus contains the herpes simplex virus thymidine kinase (TK) gene, it can The TK gene is integrated into the tumor cell genome, and the expression product of this gene can make tumor cells sensitive to the antiviral drug ganciclovir.
Further studies have found that in addition to TK gene-positive tumor cells, tumor cells that are negative for TK-negative cells are also killed in this therapy, which researchers call "bystander effect." Although the mechanism is currently unclear, it suggests that a large number of tumor cells can be killed without the need for a high transfection rate when performing treatment. At present, the treatment plan has been used in clinical trials of patients with advanced colon cancer, and has achieved good initial results.
C. Inhibition of local angiogenesis in tumors: The occurrence, development and metastasis of tumors are closely related to angiogenesis. As early as the 1970s, scholars abroad have suggested that anti-angiopathy should be used as a means of adjuvant therapy for tumors.
At present, Vascular Endothelial Growth Factor (VEGF) and its receptors are considered to be the most important factors in tumor angiogenesis, and thus become a research hotspot in the field of anti-angiogenesis of tumors. Recently, researchers abroad have introduced a signal-deficient VEGF receptor gene into advanced colon cancer tumors, and their secreted products are combined with VEGF secreted by tumor cells. It is hoped that local blood vessel formation can be prevented, and tumors lack blood supply and growth is inhibited. However, its clinical efficacy still needs further observation.
D. Enhancing tumor cell immunogenicity: a. Introducing MHC class I antigen, HLA-B7 and other genes into cancer cells. It has now been recognized that activation of T cell immunity requires a costimulatory molecule as the second signal in addition to the tumor antigen as the first signal. Studies have shown that about 20% of patients with colon cancer express MHC class I molecules, which leads to defects in tumor antigen-related T cell immune responses in these patients. Co-stimulatory molecules such as HLA-B7 also play a key role in activating T cell immune responses. effect.
By introducing a costimulatory molecule gene such as MHC class I and HLA-B7 into a cancer cell of a patient, the tumor cell can be re-identified by the immune system to initiate a cellular immune response. The expression of an exogenous allotype HLA gene on the surface of tumor cells can induce a similar host-anti-graft rejection reaction, which can also attract tumor-specific T effector cells to the tumor site, allowing these T cells to contact the tumor antigen. Sensitization, eventually killing unmodified tumor cells. b. Introducing cytokine (such as IL-2, IFN-γ, etc.) genes into cancer cells or TIL cells: using these cells to continuously secrete a small amount of cytokines in the tumor to change the local immune microenvironment to activate the local immune response, Enhance the immunogenicity of tumor antigens, promote the presentation of tumor antigens, and finally activate T effector cells to establish long-term systemic anti-tumor immunity.
This sustained small-dose mode of secretion is closer to the secretion and mode of action of cytokines under physiological conditions, while also avoiding the adverse effects of cytokines in large doses. Recently, many cytokine gene therapy protocols have been successfully registered in the United States and Western Europe, most of which introduce IL-2 genes into cancer cells via retroviruses or adenoviruses, and then return to the body to treat malignant tumors. Some researchers also injected the IL-2 gene-containing adenovirus directly into the tumor. The preliminary results showed that IL-2 receptor expression was detected on the surface of cancer cells, and tumor growth was inhibited.
E. Combination therapy: Most tumor gene therapy is safe and has no obvious side effects, but it has not yet produced satisfactory clinical efficacy and prognosis. Medical researchers at home and abroad combine different treatment models for cancer to improve the effectiveness of cancer treatment. In the case of colon cancer, it is more common to combine the chemotherapy drug fluorouracil with gene therapy. Some foreign researchers used a mouse model of colon cancer as a research object, combined with intraperitoneal injection of fluorouracil chemotherapy and local injection of biologic therapy containing p53 adenovirus particles, and the two groups were used as controls. The results show that the combination of the two methods can significantly improve the tumor suppressing effect than any of the methods alone.
prevention:
Colon cancer is the third leading cause of death in the world. Although the treatment of colon cancer has made great progress, the 5-year survival rate of advanced colon cancer has not changed much. Therefore, the significance of colon cancer prevention is becoming more and more important.
According to the multi-stage theory of the cancer process. The occurrence of colon cancer also undergoes three stages of initiation, promotion, and progression. In morphology, it is characterized by normal mucosa → hyperplasia → adenoma formation → adenoma carcinogenesis → infiltration and metastasis. If the cancer of familial adenomatous polyposis becomes a model, the natural history of colon cancer can be as long as 10 to 35 years. This provides a very favorable opportunity for the prevention of colon cancer. According to different interventions at different stages of the natural history of colon cancer, China has developed the following prevention strategies.
1. Primary prevention: Eliminate or reduce the exposure of the large intestinal mucosa to carcinogens before the tumor occurs, inhibit or block the carcinogenesis of epithelial cells, thereby preventing the occurrence of tumors. These include dietary interventions, chemoprevention, and treatment of precancerous lesions.
(1) Dietary intervention: British scholar Burkitt has long pointed out that colon cancer is a "modern disease" related to modern lifestyles and diet types. A large number of epidemiological studies, especially immigration epidemiological studies, show that colon cancer has excessive onset and energy intake, obesity, excessive intake of saturated fatty acids, decreased physical activity, dietary fiber and micronutrients (vitamins A, E, C, trace element selenium and calcium) are associated with insufficient intake.
Dietary fiber is the most studied in terms of dietary intervention. As early as the 1960s and 1970s, Burkitt discovered that colon cancer was very rare among African blacks, and the African indigenous people's diet contained a lot of dietary fiber, so he proposed that the high-fiber diet is a hypothesis of colon cancer protection factor. Subsequent studies have shown that dietary fiber can dilute or absorb carcinogens in the feces, speeding up the passage of food residues in the intestines, thereby reducing the exposure of intestinal mucosa to carcinogens in food. At the same time, dietary fiber can also protect colon cancer by changing the metabolism of bile acid, lowering the pH of the colon and increasing the production of short-chain fatty acids.
Early observational epidemiological studies and case-control studies have shown that dietary fiber has a protective effect on colon cancer with increasing intake. For example, Howe collected data from 13 case-control studies with a total of 5,287 patients and 10,470 controls, and found that 12 of these studies supported a negative correlation between dietary fiber intake and colon cancer incidence; The intake of C and beta carotene has only a small negative correlation with the onset of colon cancer.
In the prospective clinical intervention trials, such as the occurrence of colon cancer as an "end-point", long-term follow-up is required to reach a definitive conclusion, so some people advocate the use of precancerous lesions - adenoma (or recurrence) As an indicator of the risk of colon cancer, in recent years, some "intermediate markers" have been advocated to evaluate the effects of interventions, in order to greatly shorten the time required for intervention trials.
The most commonly used meta-term index is the rectal mucosal crypt sputum-labeled thymidine (HTdR) incorporation index (LI), which reflects the proliferation of cells. Studies have confirmed that LI is associated with colon cancer risk and has been widely used in diets. Evaluation of the intervention trial. In recent years, immunohistochemical assays have been established to detect the incorporation of brominated deoxyuridine (Br-UdR) and proliferating cell nuclear antigen (PCNA). These assays do not require radionuclides to reflect cell proliferation. Other intermediate indicators for evaluation included microscopic examination of abnormal crypts and microadenomas, as well as protein kinase C (PKC) and ornithine decarboxylase (ODC) activities.
For example, Alberts et al. added a 13.5 g/d wheat bran fiber to a group of 17 patients with colon cancer after surgery. The rectal crypt LI was used as an indicator, and 6 of the 8 patients with high LI were observed to have a significant decrease in LI. The total reduction rate of the whole group was 22% (P<0.001); Reddy et al found that adding 10g/d wheat bran or cellulose can effectively reduce the mutagenic activity of feces and the concentration of secondary bile acid, while oat wheat bran has no such effect. Decosse et al. found a high-fiber (>11g/d wheat bran) to reduce the recurrence of adenomas in vitamin C (4g/d) and a 4-year randomized controlled diet intervention trial in 58 patients with FAP. Vitamin E (400 mg/d) did not have this effect.
However, large-scale prospective trials completed in recent years have failed to confirm the protective effects of dietary fiber. Schatzkin et al reported that 2079 patients with a history of colon cancer were randomly divided into two groups, one group was given dietary advice and received a low-fat, high-fiber diet, and the other group was kept on a regular diet and was not consulted. Colonoscopy was found 1 to 4 years later. There was no difference in the recurrence rate of colon adenocarcinoma between the two groups. A randomized controlled study by Albert et al. in Arizona recently showed that 1429 patients with a history of colorectal adenoma were given low fiber (adding 2.0 g of wheat bran/d) and high fiber (adding 13.5 g of wheat bran/d) diet. The recurrence rate of colorectal adenomas was the same in both groups. The results were also supported by a large sample prospective cohort study by Fuchs and Giovannucci et al.
This is a health survey of 121,700 registered nurses (all women) in the United States since 1976. From 1980 onwards, the diet of each woman was investigated in a questionnaire form, and 88,777 subjects (34 to 59 years old) who met the study criteria were followed up until 1996. In the 16-year study group, 787 cases of colon cancer occurred, and 27,530 people underwent colonoscopy, and 1012 cases of colorectal adenoma were found. After analyzing the above data, after adjusting for age, total energy intake and other known risk factors, it was found that dietary fiber intake was not associated with the risk of colon cancer, and the highest fiber intake was compared with the lowest 20%. The relative risk of colon cancer was 0.95 (95% CI: 0.73 to 1.25), and no dietary fiber intake was found to be associated with colon cancer.
The Cochrane Center in Oxford, England, collected a randomized controlled trial of dietary fiber interventions until October 2001. Systemic reviews and meta-analysis were used to evaluate dietary fiber for the reduction and recurrence of colorectal adenomas. And the protective effect on colon cancer. There were 5 clinical trials that met the analytical criteria, including 4349 subjects. The analysis found that the relative risk of colorectal adenomas in the intervention group and the control group was observed by dietary supplementation with wheat bran or high-fiber diet for 2 to 4 years. ) is 1.04 (95% CI: 0.95 to 1.13), and the risk difference (RD) is 0.01 (95% CI: 0.02 to 0.04). The authors conclude that "the randomized controlled clinical trial to date does not have sufficient evidence to support increased dietary fiber intake and may reduce the occurrence or recurrence of colorectal adenomas in 2 to 4 years.
Because the interactions between the various nutrients in the diet are complex, the type of diet is more important than the specific ingredients, and dietary interventions are often not effective because of the addition of a single factor. In addition, the development of tumors is a long process. Dietary intervention is also a behavioral intervention. The protection of dietary fiber and other dietary components needs to be verified by more scientific and strict design and long-term prospective research.
(2) Chemoprevention: Chemoprevention is a new concept of tumor control proposed in recent years. It refers to the prevention of tumors by one or more natural or synthetic chemical agents, chemopreventive agents (CPA). occur. In a broad sense, dietary intervention is also a kind of chemoprevention, which can be seen as a behavioral intervention because it is achieved by changing eating habits. Chemopreventive agents prevent the onset of tumors and inhibit their development by inhibiting and blocking the formation, absorption and action of carcinogens.
According to Vogelstein's colon cancer model, colon cancer is completed from a normal mucosa, through a series of molecular biological events, with an adenoma as an intermediate stage, and finally malignant, and chemopreventive agents can repress or reverse the occurrence of adenoma at different stages. Or inhibit its progression to malignant lesions.
1 Aspirin and other non-steroidal anti-inflammatory drugs: Aspirin and other nonsteroidal ant inflammatory drugs (NSAIDs) are the most widely studied colon cancer chemopreventive agents, the main mechanism is through irreversible acetylation and competitive inhibition ring Oxidase-1 and cyclooxygenase-2 (COX-1 and COX-2) block the synthesis of prostaglandins, promote tumor cell apoptosis, and inhibit tumor angiogenesis. Thun et al. reported in 1991 that 662,424 people were taking aspirin between 1982 and 1989. Infrequent use of those who died of colon cancer was 0.77 for men and 0.73 for women. The risk of male and female dying from colon cancer was further reduced to 0.60 and 0.58, respectively. In a 2-year follow-up survey of 47,900 medical staff, the relative risk of colon cancer was 0.68, as determined by a single survey, and the “regular use” was determined according to more than 3 surveys. The relative risk is further reduced to 0.35. In the nurses' health survey of Giovannucci et al., the risk of colon cancer in 89,46 female nurses who regularly took aspirin was 0.62, and the risk of taking 20 years or more was further reduced to 0.56.
However, the role of aspirin in preventing colon cancer has not been demonstrated in randomized controlled clinical trials. In a trial of 22071 male medical staff using aspirin to prevent coronary heart disease, the relationship between aspirin and colon cancer was also analyzed. The data showed that the experimental group and the control group had no evidence of colon cancer, colon polyps or carcinoma in situ. Significant differences, according to analysis, may be related to low doses of aspirin, short duration of administration or insufficient follow-up time.
There are few reports on the protective effect of non-aspirin NSAIDs on colon cancer. A recent large-scale retrospective found that 104,217 elderly people over the age of 65 were taking prescriptions for non-aspirin NSAIDs from Medicaid. The relative risk of colon cancer is 0.61, and of course, its role should be confirmed by well-designed prospective studies.
2 folic acid: folic acid is a micronutrient in the diet, rich in vegetables and fruits, epidemiological studies found that people with high folic acid intake have a low incidence of colon cancer, while decreased folic acid intake (often seen in large drinkers) increases Risk of colon cancer and colorectal adenoma. Studies have shown that diets containing large amounts of folic acid have a protective effect on colon cancer (male RR = 0.78, female RR = 0.91), while the effect of adding folic acid to the diet is more pronounced (male RR = 0.63, female RR = 0.66). ). In Giovannucci's nurse health survey, women's daily intake of more than 400μg of folic acid has a significant protective effect on colon cancer (RR=0.25), but the protective effect will not appear until 15 years later, suggesting that folic acid is in the early stage of colon cancer. Play a role.
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Case-control and cohort studies in humans have shown that the use of high-calcium diets and calcium supplements is inversely associated with colon and colorectal adenomas, but only some of the results are statistically significant. The main reason may be that the calcium intake is not accurately estimated or is related to other dietary factors. In recent years, Baron et al reported that 930 patients with a history of colorectal adenoma were randomized to receive calcium supplements (3 g/d calcium carbonate, 1.2 g calcium) or placebo. Colonoscopy was performed at 1 year and 4 years after the start of the study. The incidence of adenoma in the calcium group was decreased, which was significantly different from the placebo group (RR=0.85). Moreover, the protective effect of calcium additive was after taking the drug. It can be observed in 1 year.
4 Estrogen: In the past 20 years, the mortality rate of colon cancer in males in the United States has been decreasing, while women are more obvious. One explanation is that women use hormone replacement therapy extensively after menopause. The mechanism by which estrogen prevents colon cancer may be related to reducing secondary bile acid production, decreasing insulin growth factor-1, or directly acting on intestinal mucosal epithelium.
Calle et al reported that colon cancer mortality was significantly lower in women who received hormone replacement therapy (RR = 0.71), and more significant in patients who continued to use for more than 11 years (RR = 0.54). Similar results were found in the nurses' health study (RR = 0.65), but the protective effects of hormones disappeared 5 years after discontinuation. The results of two meta-analyses published in recent years have also shown that hormone replacement therapy can reduce the overall risk of colon cancer by 20%. The above observations suggest that the protective effect of estrogen may occur in the late stage of colon cancer.
5 Vitamins and Antioxidants: Vitamins and antioxidants in vegetables and fruits have been thought to reduce the incidence of colon cancer for many years, but many prospective studies do not support this hypothesis. For example, nurse health research, doctor health research, etc. have not found the addition of beta carotene to the diet, vitamin A, B, D or E for colon cancer.
In a randomized controlled trial, 864 patients with a history of colorectal adenoma were given a placebo, beta carotene, vitamin C and vitamin E, and beta carotene and vitamins C and E. Colonoscopy was performed 1 year and 4 years later, and no difference was found in the 4 groups of adenomas.
(3) Treatment of precancerous lesions: Precancerous lesions of colon cancer are generally considered to include adenomatous polyps, ulcerative colitis, and Crohn's disease, and adenomas are particularly closely related to colon cancer. Epidemiology, animal experiments, and clinical and pathological studies have confirmed that the vast majority of colon cancers are cancerous from adenomas, especially large, villous, and adenomas with severe atypical hyperplasia. According to Morson's study, if the colorectal adenoma is not removed, colon cancer can occur in 4% of patients within 5 years, and 14% can be cancerous within 10 years. Stryker et al also demonstrated that untreated colorectal adenoma patients can have a colon cancer rate of up to 24% within 20 years. Therefore, early detection and timely treatment of colorectal adenoma is an ideal way to prevent and reduce the occurrence of colon cancer.
Gilbertsen began to perform sigmoidoscopy (hard-slice) examinations every year for asymptomatic people over 45 years old in the 1950s. He found that polyps were removed. A total of 18,158 people were examined in 25 years, and only 13 cases of low colon cancer occurred in the tested population. And both are early, which is 85% lower than the expected 75-80 cases. In 1976, Lee analyzed the trend of colorectal cancer in the United States for 25 years. The incidence of colon cancer increased significantly while rectal cancer decreased by 23%. In the 1950s, rectal cancer accounted for 55% of colon cancer, but in the 1970s it was only 30.7%. It is believed that the cause of the reduction in rectal cancer is likely to be the result of extensive sigmoidoscopy and active treatment of low adenomas found.
In Zhejiang Province Medical University from 1977 to 1980, colon cancer screening was conducted in Haining City over 30 years old. Two screenings completed 238 826 cases of 15cm colonoscopy, and 4076 cases of low colorectal polyps were found. 1410 cases of adenoma were surgically removed. By 1998, a total of 6 colonoscopy or 60cm fiber sigmoidoscopy (after 1988) were followed up. All the polyps detected were removed. According to Haining tumor registration data, the city's average rectal cancer from 1992 to 1996. Morbidity and mortality were 41% and 29% lower than those from 1977 to 1981, respectively.
However, the value of removing precancerous lesions for colon cancer prevention remains to be confirmed by more rigorous clinical trials. To this end, the US NCI funded a multi-center prospective clinical trial (National Polyp Study, NlPS) involving seven units including the Sloan-Kettering Memorial Cancer Center. In the NPS, 9112 patients who underwent total colonoscopy between 1980 and 1990, 2632 patients with adenomas who met the study conditions, and 1418 patients with adenoma were randomly divided into 2 groups and followed up according to different examination frequency. At the time of total colonoscopy and barium enema, the average follow-up time was 5.9 years, during which only 5 asymptomatic early colon cancers (polyposis) were found, but no invasive colon cancer. The incidence of colon cancer in this group was reduced by 90% and 88%, respectively, compared with the two reference groups in patients with polyp history without surgical removal. The incidence of colon cancer in this group also decreased by 76% compared with the general population. This study fully supports the idea that colorectal adenoma can develop into colorectal adenocarcinoma, and it proves that the treatment of precancerous lesions can prevent the occurrence of colon cancer.
2. Secondary prevention Screening for high-risk populations of colon cancer with a view to finding asymptomatic preclinical tumor patients. Early diagnosis and early treatment can improve the survival rate of patients and reduce the mortality rate of the population. Because screening can not only find early colon cancer, but also the precancerous lesion of colon cancer - adenomatous polyps, so that it can be treated in time to prevent cancer. In this sense, screening is both a secondary prevention measure for colon cancer and an effective primary prevention measure.
The natural history of colon cancer is long. From the development of precancerous lesions to invasive tumors, it is necessary to undergo molecular biological events such as multiple gene deletions and mutations. It is estimated that it takes 10 to 15 years, which provides a screening for early lesions. opportunity. Early colon cancer has a good prognosis. According to the US NCI disease surveillance (SEER) data, the 5-year survival rate of carcinoma in situ was 94.1% and the local lesion (Dukes'A) was 84.6% in 59,537 colon cancers from 1978 to 1983. When there is a distant transfer, it drops to 5.7%.
The 5-year survival rates of Dukes A, B, C, and D in 1385 colon cancers in Shanghai Cancer Hospital were 93.9%, 74.0%, 48.3%, and 0.31%, respectively. However, the proportion of A+B in the general clinical cases is usually only about 40%, while the C+D period is as high as 60%. Armitage reports that Dukes' Phase A only accounts for 6% in most hospitals in the UK. Because early colon cancer is mostly asymptomatic or the symptoms are not obvious, it has been confirmed that screening can increase the detection rate of early cases, and can also find precancerous lesions and timely treatment, thereby reducing the incidence of colon cancer. It is concluded that screening for colon cancer may reduce the mortality rate of the population. In the United States, the mortality rate of colon cancer decreased by 20.5% from 1973 to 1995, and the incidence rate decreased by 7.4%, especially after 1986. It is generally believed that this may be related to the widespread development of colon cancer screening and polyps found by colonoscopy. It is unlikely to be the result of changes in diet and lifestyle.
Recently, the United States NCI, the United States Preventive Service Task Force (USPSTF) and the American Gastroenterological Association have commonly used screening methods for colon cancer, including: anal finger test, fecal occult blood test, sigmoidoscopy, The use of gastroenterology and colonoscopy has been evaluated, and this is the most authoritative and comprehensive review of the evidence for the effectiveness of colon cancer screening.
(1) Anal diagnosis: Anal examination is simple and easy, and the rectum can be found within 8cm from the anus. About 30% of colorectal cancer in the country is within this range, but only 10% of colorectal cancer in Europe and America can be anal. Check it out. The detection rate of polyps in the sigmoid colonoscopy (15-18 cm) of colon cancer in Haining City in China was 1.7%, while the anus was only 0.17%. In addition, when the large-scale examination, the examiner's swelling and sensation of the fingertips failed, resulting in a decrease in the detection rate. A case-control study in the United States showed that patients who died of distal rectal cancer between the ages of 45 and 1971 between 1971 and 1986 had no difference in the rate of anal examinations 1 year before diagnosis compared with the control group (OR= 0.96). Therefore, anal digital examination has a limited effect as a screening method, but it is an essential part of a full physical examination for symptomatic patients.
(2) Fecal occult blood test: Intestinal non-dominant hemorrhage is the most common early symptom of colon cancer and colorectal adenoma. Since Greegor first used FOBT to screen colon cancer in 1967, due to its economy, simplicity and safety, FOBT has been The most widely used colon cancer screening method, the existing methods of occult blood test are mainly chemical and immunological methods.
In the chemical method, Hemoccult II (Smith Kline Diagnostics) is the most widely used and most studied. It uses the peroxidase-like activity of heme to react with guaiac in the presence of H2O2 to produce blue color; therefore, animal blood, red meat and some vegetables such as carrots, turnips, broccoli and certain drugs such as iron Non-steroidal antipyretic and analgesic drugs can also produce false positive reactions. It is generally believed that the normal human intestinal gastrointestinal bleeding volume is less than 2ml per day, while the Hemoccult II detection sensitivity is 4-6ml/100g stool, so FOBT positive indicates pathological bleeding.
Ransohoff and Lang systematically evaluated FOBT: the sensitivity of a single unhydrated FOBT screening colon cancer was 40%, the specificity was 96% to 98%, and the sensitivity after hydration increased to 50% to 60%, but The specificity has dropped to 90%. Recently, Lieberman et al reported that hydration FOBT screening for colon cancer sensitivity is 50% (95% CI: 30% to 70%), for cancer and precancerous lesions (large villous with atypical hyperplasia) The adenocarcinoma has a sensitivity of 24% (95% CI, 19% to 29%) and a specificity of 94% (95% CI, 93% to 95%). In the western countries, the FOBT positive rate was 2% under controlled diet conditions, and among FOBT positive patients, about 10% were colon cancer and 30% were polyps. However, the false positive rate of the chemical method FOBT (benzidine method) in the normal population of China's census can be as high as 12.10% (23706/206125), which greatly limits its application value, which may be related to other gastrointestinal bleeding diseases such as gastritis. Gastric ulcer, gastric cancer and high prevalence of sputum are related.
The earliest clinical trial of FOBT screening for colon cancer was hosted by the Sloan-Kettering Memorial Cancer Center from 1975 to 1985. 21,756 asymptomatic individuals over 40 years of age were screened, randomized to the screening group and the control group, in the colon Among the cancers, 65% of the screening group were Dukes'A and B, while the control group was only 33%; the 10-year survival rate of the screening group was significantly higher than that of the control group (P<0.001), and the colon of the screening group was followed up for 10 years. The cancer mortality rate was 43% lower than that of the control group (P=0.053). The study showed an increase in the proportion of early cancer, prolonged survival and decreased colon cancer death. The use of FOBT for screening colon cancer can reduce the mortality of colon cancer. It has been proved by at least three well-designed large-scale randomized controlled clinical trials. It is a type I evidence, so the USPSTF first defined it as a category A recommendation ( That is strongly recommended) for crowd screening.
(3) Immunology: FOBT was developed in the late 1970s. The specific immune response of hemoglobin and corresponding antibodies avoids the disadvantages of chemical methods that limit diet and improves the specificity and sensitivity of screening. In 1987, Zhejiang Medical University successfully developed the reverse indirect hemagglutination (RPHA-FOBT) kit. In Haining City and Jiashan County, Zhejiang Province, a group of 3034 high-risk populations with a history of rectal polyps were screened for RPHA FOBT. 11 cases of colorectal malignant tumor, 465 cases of polyps (195 cases of adenoma), with 60cm fiber enteroscopy as the reference standard, proved that the sensitivity of RPHA-FOBT screening for colon cancer was 63.6%, specificity was 81.9%, Youden The index is 0.46, which is superior to the chemical method.
The study also showed that the sensitivity of RPHA-FOBT screening polyps was only 22.1%, but it was about 40% positive for villous and tubular villous adenomas with a high malignant tendency. On this basis, Zheng Shu et al. used a sequential method for colon cancer screening in 75,813 people over the age of 30 in Jiashan County, a high incidence area for colon cancer. The total positive rate of RPHA-FOBT was 4.2%, and 21 cases of colon were screened. Dukes' A and B in cancer accounted for 71.4%.
A variety of immunological FOBT reagents are available in the United States, such as Hemeselect, InSure, and FlexsureOBT, which use monoclonal or polyclonal antibodies against human hemoglobin to detect fecal occult blood. One of the high-risk groups of 240 colon cancers with InSure TM reagent showed that InSureTM had a sensitivity of 87% (20/23) for screening for colon cancer and 47.4% for adenomas >10 mm. (9/19), the specificity of detection in a group of normal people over 40 years old was 97.9% (88/98), and the specificity of the normal population under 30 years old was 97.8% (92/94).
Studies have shown that the immunological method FOBT including InSureTM does not react with myoglobin, animal hemoglobin, is not interfered by diet and drugs, and is negative for feces of upper gastrointestinal bleeding. Recently, the American Cancer Society (ACS) Colon Cancer Advisory Group evaluated the available evidence that immunological FOBT can increase the specificity of screening compared to chemical FOBT, adding the following in the 2003 ACS Colon Cancer Screening Guidelines. Note: "In the detection of fecal occult blood, the immunological occult blood test is easy for patients to accept, its sensitivity and specificity is better than or at least the same."
(3) Sigmoidoscopy: Gilbertsen began to screen colon cancer and polyps with sigmoidoscopy in the early 1950s, and sigmoidoscopy (25cm hard) was performed on 18,158 people. After 25 years of follow-up, the national average was found. In contrast, the incidence of sigmoid colon and rectal cancer in the screening group decreased significantly. Due to the difficulty in inserting the rigid colonoscopy, the patient acceptance rate is low. Since the invention of the optical fiber colonoscopy in 1969, the 60cm fiberoptic colonoscopy was introduced into the clinic in 1976. Now the 25cm hard lens has been replaced by the 60cm fiber enteroscopy. More than 80% of family physicians have equipped and used 60cm colonoscopy.
The Kaiser Permanence Multiphasic Health Checkup (MHC) in the United States randomly divided 10,713 people aged 35 to 54 into trials and controls. Among the 5156 people who were screened, 20 cases of colon cancer were detected, and Dukes' A stage accounted for 60%. After 16 years of follow-up, the 5-year survival rate was 90%, and the 10-year survival rate was 80%. The control group Dukes 'A phase is only 48%, and the 10-year survival rate is also 48%. The number of colon cancer deaths in the experimental group was significantly smaller than that in the control group (12 and 29, respectively). However, further analysis found that, if only the colon cancer mortality rate was within the range that can be achieved by colonoscopy, the difference between the experimental group and the control group was not statistically significant.
Lieberman et al found that 70% to 80% of patients with distal colonic polyps in the fiberoptic colonoscopy also had new organisms in the proximal colon. A randomized controlled trial found that in patients with polyps detected by colonoscopy, the incidence of colon cancer was reduced by 80% after a complete colonoscopy and removal of the adenomas found. Therefore, 60cm fiber enteroscopy for screening can not only remove precancerous lesions within the reach of the endoscope, and can be used as an indication for full colonoscopy, which can reduce the incidence of all colon cancer. Experts believe that if colonoscopy is found to have polyps, the indications for further colonoscopy should be as follows: patients over 65 years old; villi or ≥1 cm or multiple adenomas; family history of colon cancer.
According to the statistics of 3147 colon cancers in China, 82% occur below the splenic spleen, that is, the 60cm colonoscopy is accessible. Therefore, its application value seems to be larger than that of Western countries. The Cancer Research Institute of Zhejiang Medical University used 60cm fiber enteroscopy as a rescreening method for sequential screening of colon cancer. 60cm colonoscopy was performed on 36.2 high-risk groups, and 21 cases of colon cancer and 331 polyps were found. In another group of 3034 high-risk subjects, 11 cases of colorectal malignant tumors and 563 cases of polyps were detected by 60cm colonoscopy. Before the 60cm colonoscopy, mannitol powder and plenty of drinking water were used for intestinal preparation. The intestinal cleanliness was satisfactory or basically satisfactory in 95%, and all of the more than 6,000 colonoscopy examinations did not have a perforation. According to China's national conditions, 60cm fiber enteroscopy can not be used as a primary screening method, but as a simple, feasible and relatively reliable rescreening or diagnostic measures is still worth promoting.
At least two case-control studies have shown that sigmoidoscopy can reduce the mortality of colon cancer. In Selby's study, sigmoid colonoscopy is used, while Newcomb's study is mainly fiberoptic colonoscopy. Both studies showed that those who had had more than one colonoscopy had a 70% to 90% reduction in the risk of dying from distal colon and rectal cancer than those who had never had a microscopy.
According to Thiis-Evensen et al., 799 subjects were randomly selected from the Norwegian general population in 1983 and randomly divided into the colonoscopy group and the control group. 81% of the screening group received a colonoscopy, such as polyps. mirror. 13 years later (1996), 451 (71%) of the 2 groups underwent total colonoscopy and found no difference in the incidence of polyps between the screening group and the control group, but the screening group had high-risk polyps (≥1 cm, with atypical The incidence of hyperplasia was lower than that of the control group (RR=0.6, 95% CI: 0.3-1.0, P=0.07), and another 2 cases of colon cancer occurred in the registered screening group and 10 cases in the control group (RR=0.2, 95% CI: 0.03 to 0.95). However, because the overall mortality rate of the screening group is greater than that of the control group (mainly due to cardiovascular disease death), it is difficult to conclude that the colonoscopy screening is conducive to reducing the mortality rate of colon cancer. Currently, there are two randomized controlled trials of sigmoidoscopy screening for colon cancer in the United Kingdom and the United States. Despite the lack of reliable evidence for the efficacy of sigmoidoscopy in the screening of colon cancer, ACS and USPSTF still recommend 60 cm fiberoscopy as one of the primary means of colon cancer screening.
(4) Total colonoscopy: Colonoscopy screening with colonoscopy alone has reduced the incidence and mortality of colon cancer. The results of clinical trials are not confirmed, but full colonoscopy is often combined with other screening methods such as FOBT or sigmoidoscopy. The effect on reducing the incidence and mortality of colon cancer is clear. Lieberman and Imperiale have shown that half of patients with progressive neoplasms (≥1 cm in diameter, villous adenomas and carcinomas with atypical hyperplasia) have no distal colon and rectal polyps. The need for a full colonoscopy as a screening tool. However, colonoscopy is expensive, preparation is complicated, patient acceptance is poor, and there is a certain complication rate (several complication rate is about 0.3% of perforation bleeding, and the mortality rate is about 1/20000). Therefore, it is reasonable to use colonoscopy alone for screening. Sex is subject to further verification.
(5) Gastric double contrast enema: Although the ACS recommendation used a double contrast enema (DCBE) as a screening method for colon cancer every 5 years, no studies have shown that DCBE is effective in reducing the incidence and death of colon cancer. Winawer et al. used the national polyp study data, the results of total colonoscopy as the gold standard, DCBE evaluation, found that the sensitivity of <0.5cm polyp DCBE is 32%, 0.6 ~ 1cm polyps is 53%, >1cm polyps (including 2 cases of cancerous polyps) were 48%, while DCBE specificity was 85%. Although the sensitivity of DCBE is low, it can be examined in the whole colon, and the complication rate is low. It is widely accepted by medical staff and patients, so it can still be used as one of the screening methods for colon cancer.
(6) Other technologies: In response to recent new technologies for detecting colon cancer and adenomatous polyps, the American Cancer Society's Colon Cancer Advisory Group (ACS Colorectal Cancer Advisory Group) held a seminar in April 2002 on CT colorectal The effects of imaging, immunological fecal occult blood test, fecal molecular markers, and capsule video endoscopy in colon cancer screening were evaluated and agreed.
CT Colonography, also known as virtual colonoscopy, began in 1994. It is a rapid multi-scan of spiral CT, which is a two-dimensional or three-dimensional imaging of the internal structure of the colon, simulating the results of colonoscopy, but Invasive operation of the colonoscope is avoided. According to the results of several central studies in the United States, the sensitivity of CT colorectal imaging of >1 cm is close to 90%, while it is reduced to about 50% for <0.5cm, and 100% for colon cancer. No false positives.
The colon cancer process involves multiple gene mutations, and the mutated DNA in the tumor cells and their precursor cells is exfoliated and can be detected from the feces by PCR amplification. Detection of colon cancer using mutant DNA in feces as a molecular marker is a new technology developed in recent years. The mutant DNA detection kit developed by EXACT detects 15 common mutation sites of colon cancer including K-ras, APC and p53 genes and mutation points on the microsatellite instability marker bat-26. In a small sample double-blind trial, 61 subjects included 22 colon cancers, 11 large adenomas, and 128 normal subjects. The sensitivity of fecal mutant DNA to colon cancer was 91%, the sensitivity of adenoma was 82%, and the specificity was 93%. If K-ras mutation was not included, the sensitivity of intestinal cancer remained unchanged, and the adenoma decreased to 73. %, while the specificity increased to 100%.
The advisory team reviewed these new technologies and reached unanimous conclusions: CT colorectal imaging and fecal mutant DNA testing are promising new technologies, but there is currently no sufficient evidence to recommend screening as a means of screening. Its sensitivity and specificity are superior to or equal to the chemical method, and it is more convenient for patients. Capsule video endoscopy is not suitable for colon cancer and polyps because its design is limited to the upper digestive tract and small intestine.
(7) Screening program: In 1980, the American Cancer Society (ACS) proposed a guideline for colon cancer screening. Although it has been revised several times, the basic points have not changed. The American Gastroenterological Association, a high-risk group for colon cancer, proposes a stratified screening program for colon cancer risk.
1 In view of the relatively low incidence of colon cancer in China, the age of onset is advanced, and health resources are limited, the ACS program is difficult to implement in China. On the basis of previous work, Zheng Shu et al proposed a sequential screening method for colon cancer.
A. Using the questionnaire as a quantitative assessment of the risk of colon cancer, calculate the AD value of the risk of colon cancer in each subject, with AD ≥ 0.3 as the positive threshold; and RPHA FOBT for the subject, 2 The project initially screened out high-risk groups.
B. Re-screening for high-risk groups with 60cm fiber enteroscopy.
C. 60cm colonoscopy patients with FOBT follow-up, FOBT continued positive is recommended for full colonoscopy and / or gas sputum double contrast.
2 Using this model, among the 75 813 people over 30 years old in Jiashan County, the high-risk population was screened out, 4299 people were screened for high-risk population, 3162 cases (73.6%) of 60cm colonoscopy were completed, and 21 cases of colon cancer were detected, of which colon cancer accounted for 62%. Dukes A+B accounted for 71.4%. On the basis of the promotion of the program, the inspectors proposed a further optimization plan:
A. Screening subjects ≥ 40 years old.
B. The following 1 should be used for 60cm fiberoscopy: RPHA FOBT positive; first-degree relatives have colon cancer history; I have a history of cancer in the past; 2 or more of the following symptoms, such as chronic constipation, mucus and blood, chronic Diarrhea, history of intestinal polyps, chronic appendicitis, history of mental stimulation.
C. If the 60cm colonoscopy is negative, the FOBT review is positive, and a full colonoscopy or gas sputum double contrast should be performed.
Calculate the AD value of the risk of colon cancer in each subject, with AD ≥ 0.3 as the positive threshold; and RPHA FOBT for the subjects, which are used to screen out high-risk groups.
D. Re-screening with high-risk groups with 60cm fiber enteroscopy.
E.60cm colonoscopy patients with FOBT follow-up, FOBT continued positive is recommended for full colonoscopy and / or gas sputum double contrast.
3. Three-level prevention actively treats patients with clinical cancer to improve their quality of life and prolong survival.
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