Colon cancer is the 3rd leading cause of death in the world, and despite great advances in the treatment of colon cancer, the 5-year survival rate of advanced colon cancer has not improved much over the years. Therefore, the significance of colon cancer prevention has become more and more important.
According to the multi-stage theory of cancer process. The occurrence of colon cancer also goes through three stages: initiation, promotion and progression. Morphologically, it is normal mucosa → hyperplasia → adenoma formation → adenoma carcinoma → infiltration and metastasis. If the carcinogenesis of familial adenomatous polyposis is used as a model, the natural history of colon cancer can be as long as 10-35 years. This provides an extremely favorable opportunity for colon cancer prevention. According to different interventions in different stages of the natural history of colon cancer, the following prevention strategies have been developed in China.
1. Primary prevention: Before the occurrence of tumor, eliminate or reduce the exposure of colonic mucosa to carcinogenic agents to inhibit or block the carcinogenic process of epithelial cells, so as to prevent the occurrence of tumor. These measures include dietary intervention, chemoprevention and treatment of precancerous lesions.
(1) Dietary intervention: British scholar Burkitt has long pointed out that colon cancer is a “modern disease”, which is related to modern lifestyle and diet type. A large number of epidemiological studies, especially epidemiological studies on immigrants, show that the development of colon cancer is related to excessive energy intake, obesity, excessive saturated fatty acid intake, reduced physical activity, and insufficient intake of dietary fiber and micronutrients (vitamins A, E and C, trace elements selenium and calcium).
In terms of dietary interventions, dietary fiber has been the most studied. Back in the 1960s and 1970s Burkitt found that colon cancer was rare in black Africans and that the diets of African indigenous people contained a high amount of dietary fiber, so he proposed the hypothesis that a high fiber diet was a protective factor against colon cancer. Subsequently, numerous studies have concluded that dietary fiber can dilute or absorb carcinogens in feces and speed up the passage time of food residues in the intestine, thus reducing the exposure of intestinal mucosa to carcinogens in food. Also dietary fiber may provide protection against colon cancer by altering the metabolism of bile acids, 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 a corresponding increase in the protective effect of dietary fiber against colon cancer with increasing intake. For example, Howe pooled data from 13 case-control studies totaling 5,287 patients and 10,470 controls and found that 12 of these studies supported a negative association between dietary fiber intake and colon cancer incidence; it also found only a small negative association between vitamin C and beta carotene intake and colon cancer incidence after adjusting for confounding factors.
Given that in prospective clinical intervention trials, the occurrence of colon cancer as an “end-point indicator” requires long-term follow-up before a definite conclusion can be drawn, the occurrence (or recurrence) of precancerous lesions – adenomas – has been advocated as an indicator of colon cancer risk, and in recent years, some “intermediate indicators” (inter-points) have been advocated. In recent years, some “intermediate markers” have been advocated to evaluate the effect of interventions in order to greatly reduce the time required for intervention trials.
The most commonly used intermediate marker is the rectal mucosal crypt tritium-labeled thymidine nucleoside (HTdR) admixture index (LI), which reflects the proliferation status of the cells, and studies have confirmed that LI is associated with the risk of colon cancer and has been widely used in the evaluation of dietary intervention trials. In recent years, immunohistochemical tests have been established to detect the rate of bromodeoxyuridine nucleoside (Br-UdR) incorporation and proliferating cell nuclear antigen (PCNA), which can also reflect the proliferation status of cells without the use of radionuclides. Some other intermediate indicators used for evaluation include microscopic findings of abnormal crypt and microadenoma and protein kinase C (PKC) and ornithine decarboxylase (ODC) activities.
For example, Alberts et al. added 13.5 g/d bran fiber to the diet of a group of 17 tumor-free patients after colon cancer surgery, and observed a significant decrease in LI in 6 of the 8 cases with high LI, with an overall decrease of 22% in the whole group (P<0.001); Reddy et al. found that the addition of 10 g/d bran or fiber was effective in reducing fecal mutagenic activity and In a 4-year randomized controlled dietary intervention trial of 58 patients with FAP, Decosse et al. found that high fiber (>11 g/d bran) reduced adenoma recurrence, whereas vitamin C (4 g/d) and vitamin E (400 mg/d) did not.
Schatzkin et al. reported that 2,079 patients with a history of colon cancer were randomized into 2 groups, one group was given dietary counseling and received a low-fat, high-fiber diet, and the other group maintained a regular diet without counseling. In a recent randomized controlled study completed by Albert et al. in Arizona, USA, 1429 patients with a history of colorectal adenoma were given a low-fiber (2.0 g bran/d added) and high-fiber (13.5 g bran/d added) diet, and the recurrence rate of colorectal adenoma was the same in both groups. a large sample of patients in a prospective cohort study by Fuchs and Giovannucci et al. A prospective cohort study by Fuchs and Giovannucci et al. supports these results. This was a health survey of 121,700 registered nurses (all women) in the United States that began in 1976. A total of 787 cases of colon cancer occurred in this cohort over 16 years, and colonoscopy was performed on 27,530 individuals and 1012 cases of colorectal adenomas were found. Analysis of the above data, after adjusting for age, total energy intake and other known risk factors, revealed no correlation between dietary fiber intake and the risk of colon cancer, with a relative risk of colon cancer of 0.95 (95% CI: 0.73-1.25) compared to the highest and lowest 20% quartiles of fiber intake, and again no correlation was found between dietary fiber intake and the occurrence of colon cancer.
The Cochrane Centre in Oxford, UK, collected all randomized controlled studies of dietary fiber interventions up to October 2001 and evaluated the protective effect of dietary fiber on reducing the incidence and recurrence of colorectal adenomas and on the development of colon cancer using systematic review and meta-analysis. A total of 5 clinical trials including 4349 study subjects that met the analysis criteria found that the relative risk ratio (RR) of colorectal adenoma development in the intervention group versus the control group was 1.04 (95% CI: 0.95 to 1.13) and the risk difference (RD) was 0.01 (95% CI: 0.02 to 0.04) after 2 to 4 years of dietary intervention with bran or a high fiber combination diet. ). The authors concluded that “to date, there is insufficient evidence from randomized controlled clinical trials to support that increased dietary fiber intake reduces the incidence or recurrence of colorectal adenomas over 2 to 4 years.
Because of the complexity of the interactions between nutrients in the diet, the type of diet is more important than the specific components, and dietary interventions are often not effective with the addition of a single factor. The protective effects of dietary fiber and other dietary components need to be validated with more scientific and rigorous designs and long-term prospective studies.
(2) Chemoprevention: Chemoprevention is a new concept of tumor control proposed in recent years, which refers to the use of one or more natural or synthetic chemical agents, i.e., chemopreventive agent (CPA), to prevent the occurrence of tumors. In a broader sense, dietary intervention is also a kind of chemoprevention, because it is achieved by changing dietary habits, so it can also be regarded as a behavioral intervention. Chemopreventive agents can prevent the development of tumors and inhibit their progression by inhibiting and blocking the formation, absorption and action of carcinogenic agents.
According to Vogelstein’s model of colon carcinogenesis, colon cancer is completed from normal mucosa, through a series of molecular biological events, with adenoma as an intermediate stage, and finally malignancy, and chemopreventive agents can deter or reverse the development of adenoma or inhibit its progression to malignant lesions at different stages (Figure 13).
①Aspirin and other non-steroidal anti-inflammatory drugs: Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) are the most widely studied chemopreventive agents for colon cancer, whose main mechanism is to block the development of adenoma through irreversible acetylation and competitive inhibition of cyclooxygenase-1 and cyclooxygenase-2 (COX-1 and Thun et al. 1991 reported that the risk of dying from colon cancer was 0.77 for men and 0.73 for women among infrequent versus non-frequent users of aspirin in a survey of 662,424 individuals between 1982 and 1989. In a 2-year follow-up survey of 47,900 health care workers, the relative risk of colon cancer was 0.68 for regular aspirin users, as determined by a single survey, and 0.58 for “regular users”, as determined by more than 3 surveys. “In a survey of nurses’ health by Giovannucci et al. it was also found that the risk of colon cancer among 89,446 female nurses who took aspirin regularly was 0.62, and the risk was further reduced to 0.56 for those who took it for more than 20 years.
However, the role of aspirin in preventing the development of colon cancer has not been demonstrated by randomized controlled clinical trials. In a trial of 22,071 male health professionals who used aspirin to prevent coronary heart disease and also analyzed the relationship between aspirin and colon cancer, the data showed no significant difference in the occurrence of colon cancer, colon polyps, or carcinoma in situ between the trial and control groups, which was analyzed to be possibly related to low doses of aspirin, short duration of continuous use, or insufficient follow-up.
There are fewer reports on the protective effect of non-aspirin NSAIDs on colon cancer. A recent retrospective survey of a large sample of 104,217 elderly people aged 65 years or older who took non-aspirin NSAIDs from Medicaid prescriptions found that their relative risk of colon cancer was 0.61, although the effect should be confirmed by a well-designed prospective study. (i) Folic acid
Folic acid: Folic acid is a micronutrient in the diet and is abundant in vegetables and fruits. Epidemiological studies have found a low incidence of colon cancer in populations with high folate intake, while reduced folate intake (often seen in heavy drinkers) increases the risk of colon cancer and colorectal adenomas. Studies have shown that diets containing high amounts of folic acid are protective against colon cancer (RR=0.78 for men and RR=0.91 for women), and adding folic acid to the diet is even more effective (RR=0.63 for men and RR=0.66 for women). In Giovannucci’s Nurses’ Health Survey women consuming more than 400 μg of folic acid per day had a significant protective effect against colon cancer (RR=0.25), but this protective effect was not apparent until after 15 years of use, suggesting that folic acid acts in the early stages of colon carcinogenesis.
(iii) Calcium: Most of the case-control and cohort studies done in humans showed a negative association between a high-calcium diet and the application of calcium additives and the development of colon cancer and colorectal adenomas, but only some of the results were statistically significant. The main reason for this may be imprecise estimation of calcium intake or a confounding effect with other dietary factors. In recent years, Baron et al. reported that 930 patients with a history of colorectal adenoma were randomized to 2 groups taking a calcium supplement (3 g/d calcium carbonate with 1.2 g of component calcium) or placebo. Colonoscopy was performed 1 and 4 years after the start of the study, and there was a decrease in the incidence of adenomas in the group taking calcium tablets, with a significant difference from the placebo group (RR=0.85), and the protective effect of calcium additive was observed 1 year after taking the drug.
④Estrogen: One explanation for the declining trend in colon cancer mortality in men in the United States over the past 20 years, and more significantly in women, is the widespread use of hormone replacement therapy in women after menopause. The mechanism by which estrogen prevents colon cancer may be related to a reduction in secondary bile acid production, a decrease in insulin growth factor-1 (IGF-1), or direct action on the intestinal mucosal epithelium.
Calle et al. reported a significant reduction in colon cancer mortality in women on hormone replacement therapy (RR=0.71), and more significantly in those on continuous use for more than 11 years (RR=0.54). Similar results were found in the Nurses’ Health Study (RR=0.65), but the protective effect of hormones disappeared 5 years after discontinuation of the drug. The results of 2 meta-analyses published in recent years also showed that hormone replacement therapy resulted in an overall 20% reduction in the risk of colon cancer. The above observations suggest that the protective effect of estrogen may occur in the later stages of colon cancer.
⑤ Vitamins and antioxidants: It has been thought for many years that vitamins and antioxidants in vegetables and fruits may reduce the incidence of colon cancer, but several prospective studies do not support this hypothesis. For example, the Nurses’ Health Study, Physicians’ Health Study, etc. did not find a protective effect of adding beta carotene, vitamins A, B, D or E to the diet against colon carcinogenesis.
In a randomized controlled study, 864 patients with a history of colorectal adenoma were given placebo, beta carotene, vitamins C and E, and beta carotene combined with vitamins C and E. Colonoscopy at 1 year and 4 years did not find differences in adenoma development among the four groups.
(3) Treatment of precancerous lesions: It is generally believed that precancerous lesions of colon cancer include adenomatous polyps, ulcerative colitis and Crohn’s disease, and adenomas are particularly closely related to colon cancer. Epidemiological, animal studies as well as clinical and pathological studies confirm that the majority of colon cancers arise from adenomas, especially large, villous adenomas with severe atypical hyperplasia are more likely to become cancerous. According to Morson’s study, colon cancer can occur in 4% of patients within 5 years and 14% within 10 years if colorectal adenomas are not removed, and Stryker et al. also demonstrated that the incidence of colon cancer in patients with untreated colorectal adenomas can be as high as 24% within 20 years. Therefore, early detection and timely treatment of colorectal adenomas is the ideal way to prevent and reduce the occurrence of colon cancer. Gilbertsen began to perform sigmoidoscopy (rigidoscopy) once a year for asymptomatic people over 45 years old in the 1950s, and polyps were removed if found. 18,158 people were examined in 25 years, and only 13 cases of low-grade colon cancer occurred in the examined population, and all of them were early, which was 85% less than the expected 75-80 cases. In 1976, Lee analyzed the trend of colorectal cancer incidence in the United States over a 25-year period and found that the incidence of colon cancer had increased significantly while rectal cancer had decreased by 23%, with rectal cancer accounting for 55% of colon cancer in the 1950s and only 30.7% in the 1970s. It is believed that the decrease in rectal cancer is likely to be the result of widespread sigmoidoscopy and aggressive treatment of low-level adenomas found.
From 1977 to 1980, Zhejiang Medical University in China conducted colon cancer screening for people over 30 years old in Haining, and completed 238,826 cases of 15cm rectoscopy in two screening examinations, and found 4076 cases of low-level colorectal polyps, of which 1410 adenomas were removed surgically. According to the tumor registration data of Haining, the average incidence and mortality rate of rectal cancer in the city from 1992 to 1996 decreased by 41% and 29%, respectively, compared with those from 1977 to 1981.
However, the value of removing precancerous lesions for colon cancer prevention has yet to be confirmed by more rigorous clinical trials. To this end, the NCI in the United States funded a multicenter prospective clinical trial (National Polyp Study, NlPS) involving seven units, including Sloan-Kettering Memorial Oncology Center. Of the 9112 patients who underwent total colonoscopy between 1980 and 1990 and 2632 patients with adenomas who were eligible for the study, 1418 of them were randomized into 2 groups with different frequency of examination after removal of adenomas, and total colonoscopy and barium enema were performed at follow-up. and no invasive colon cancer. The incidence of colon cancer was reduced by 90% and 88%, respectively, in this group compared with the two reference groups of patients with a history of polyps that were not surgically removed. The incidence of colon cancer in this group was also reduced by 76% compared to the general population. This study fully supports the view that colorectal adenoma can develop into colorectal adenocarcinoma, and further proves that the treatment of precancerous lesions can prevent the occurrence of colorectal cancer.
2.Secondary prevention: screening for people at high risk of colon cancer with a view to detecting asymptomatic preclinical tumor patients. To achieve early diagnosis and early treatment, improve the survival rate of patients and reduce the death rate of the population. Since screening tests can not only detect early colon cancer, but also adenomatous polyps, a precancerous lesion of colon cancer, they can be treated in time to prevent the occurrence of cancer. In this sense, screening is not only a secondary prevention measure for colon cancer, but also an effective primary prevention tool.
The natural history of colon cancer is long, from precancerous lesion to infiltrative tumor after several molecular biological events such as gene deletion and mutation, which is estimated to take 10-15 years, which provides an opportunity for screening to detect early lesions. The prognosis of early colon cancer is good. According to the data of NCI Disease Surveillance (SEER) in the United States, among 59,537 cases of colon cancer from 1978 to 1983, the 5-year survival rate of carcinoma in situ was 94.1% and that of local lesions (Dukes’ A) was 84.6%, while it decreased to 5.7% when there were distant metastases (Table 5).
The 5-year survival rates of Dukes’ A, B, C and D stages among 1385 cases of colon cancer in Shanghai Cancer Hospital in China were 93.9%, 74.0%, 48.3% and 0.31%, respectively. However, the proportion of stage A+B in general clinical cases is often only about 40%, while stage C+D is as high as 60%. armitage reported that stage Dukes’ A accounted for only 6% in most hospitals in the UK. Since early stage colon cancer is mostly asymptomatic or asymptomatic, it has been confirmed that screening can increase the detection rate of early stage cases, and at the same time, precancerous lesions can be detected and treated in time, thus reducing the occurrence of colon cancer. Thus, it is inferred that screening for colon cancer has the potential to reduce the mortality rate of the population. In the United States, the death rate of colon cancer decreased by 20.5% and the incidence rate decreased by 7.4% from 1973 to 1995, especially the rate of decrease accelerated after 1986, which is generally believed to be related to the widespread implementation of colon cancer screening and removal of polyps found by colonoscopy, and is unlikely to be the result of changes in diet and lifestyle habits.
Recent studies by the NCI, the United States Preventive Service Task Force (USPSTF), and the American Gastroenterological Association (AGA) on common means of colon cancer screening, including. Anal finger examination, fecal occult blood test, sigmoidoscopy, barium enema and colonoscopy, which is the most authoritative and comprehensive review of the evidence to date on the effectiveness of screening for colon cancer.
(1) Anal examination: Anal examination is simple and easy, and it can examine the rectum within 8cm from the anus, and about 30% of colorectal cancers in China are within this range, but only 10% of colorectal cancers in Europe and America can be detected by anal examination. The detection rate of polyps in sigmoidoscopy (15-18cm) of colon cancer screening in Haining City, China is 1.7%, while the rate of anorectal diagnosis is only 0.17%. Coupled with the loss of sensation of swelling at the fingertip of the examiner during mass examination, this caused a decrease in detection rate. In a case-control study in the United States, there was no difference in the rate of patients aged 45 years or older who died of distal rectal cancer between 1971 and 1986 compared with controls who underwent anoscopy 1 year before diagnosis (OR=0.96). Therefore, anal examination is of limited use as a screening test, but is clinically essential as part of a general physical examination of symptomatic patients.
(2) Fecal occult blood test (FOBT): Intestinal insignificant bleeding is the most common early symptom of colon cancer and colorectal adenoma. Since Greegor first used FOBT to screen colon cancer in 1967, FOBT has been the most widely used means to screen colon cancer due to its economy, simplicity and safety.
Among the chemical methods, Guaifenesin Hemoccult Ⅱ (Smith Kline Diagnostics) is the most widely used and studied. It uses the peroxidase-like activity of heme in the presence of H2O2 to produce a blue color in reaction with guaiac; therefore, animal blood, red meat and some vegetables such as carrots, turnips, cauliflower and certain drugs such as iron and non-steroidal antipyretic analgesics can also produce a false positive reaction. It is generally believed that the amount of physiological bleeding in the intestines of normal people is less than 2ml per day, while the sensitivity of Hemoccult II is 4-6ml/100g stool, so a positive FOBT indicates pathological bleeding. Recently, Lieberman et al. reported that the sensitivity of hydrated FOBT for screening colon cancer was 50% (95% CI: 30%-70%), the sensitivity for cancer and precancerous lesions (large villous adenocarcinoma with atypical hyperplasia) was 24% (95% CI, 19%-29%), and the specificity was 94% (95% CI, 93%). 94% (95% CI, 93% to 95%). In Western countries, the rate of FOBT positivity in people over 50 years of age under controlled diet is 2%, and about 10% of those positive for FOBT are colon cancer and 30% are polyps. However, the false-positive rate of chemical FOBT (benzidine method) can be as high as 12.10% (23,706/206,125) among normal people in our census, which greatly limits its application, which may be related to the high prevalence of other gastrointestinal bleeding diseases such as gastritis, gastric ulcer, gastric cancer and hemorrhoids in the national population.
The earliest clinical trial of FOBT for colon cancer screening was conducted by Sloan-Kettering Memorial Cancer Center from 1975 to 1985, in which 21,756 asymptomatic people over 40 years of age participated in the screening test and were randomly divided into a screening group and a control group. The 10-year survival rate was significantly higher in the screening group than in the control group (P<0.001), and the death rate of colon cancer in the screening group decreased by 43% compared with the control group after 10 years of follow-up (P=0.053). This study showed a consistent increase in the proportion of early cancers, longer survival and a decrease in colon cancer deaths. The effectiveness of FOBT for screening colon cancer in reducing colon cancer mortality has been demonstrated by at least three well-designed large-scale randomized controlled clinical trials (Table 6), which is Class I evidence, and therefore the USPSTF prioritized it as a Class A recommendation (i.e., strongly recommended) for population screening.
(3) Immunoassay: FOBT was developed at the end of the 1970s, using the specific immune reaction between hemoglobin and the corresponding antibodies, avoiding the disadvantages of the chemical method that requires dietary restriction and improving the specificity and sensitivity of the screening test. In 1987, Zhejiang Medical University successfully developed the reverse indirect hemagglutination method (RPHA-FOBT) kit, and detected 11 cases of colorectal malignancies and 465 cases of polyps (including 195 cases of adenomas) in a group of 3034 high-risk people with a history of rectal polyps in Haining City and Jiashan County, Zhejiang Province, using 60 cm fiberoptic colonoscopy as the reference standard. The sensitivity of RPHA-FOBT screening for colon cancer was 63.6%, the specificity was 81.9%, and the Youden index was 0.46, all of which were better than the chemical method. This study also showed that the sensitivity of RPHA-FOBT screening for polyps was only 22.1%, but it had a positive rate of about 40% for villous and tubular villous adenomas with a high propensity for malignant transformation. On this basis, Zheng Shu et al. performed colon cancer screening by sequential method in 75,813 people over 30 years of age in Jiashan County, an area with a high incidence of colon cancer, and the overall positive rate of RPHA-FOBT was 4.2%, with Dukes’ A and B stages accounting for 71.4% of the 21 colon cancer cases screened.
Several immunoassay FOBT reagents are available in the United States, such as Hemeselect, InSure, and FlexsureOBT, all of which apply anti-human hemoglobin monoclonal or polyclonal antibodies to detect fecal occult blood.1 The sensitivity of InSureTM for screening colon cancer was 87% (20/23) in a group of 240 people at high risk for colon cancer using InSure TM reagents. 87% (20/23), 47.4% (9/19) for adenomas >10 mm, and 97.9% (88/98) specificity in a group of normal people over 40 years of age and 97.8% (92/94) in a group of normal people under 30 years of age. Studies have demonstrated that immunoassay FOBT, including InSureTM, does not react with myoglobin, animal hemoglobin, is not interfered with by diet or drugs, and is negative for feces from upper gastrointestinal bleeding. Recently, the American Cancer Society (ACS) Colon Cancer Advisory Panel evaluated the available evidence and concluded that immunoassay FOBT may increase the specificity of screening tests compared to chemical FOBT, adding the following statement to the 2003 ACS Guidelines for Colon Cancer Screening: “In the detection of fecal occult blood, the immunoassay occult blood test is readily acceptable to patients and its sensitivity and specificity It is superior to or at least as sensitive as the guaiac method.”
(3) Sigmoidoscopy: Gilbertsen began screening for colon cancer and polyps with sigmoidoscopy as early as the early 1950s, and regular sigmoidoscopy (25 cm rigid) was performed on 18,158 people, and after 25 years of follow-up, the incidence of sigmoid and rectal cancer was found to be significantly lower in the screening group compared to the national average. Due to the difficulty of inserting rigid sigmoidoscope and low patient acceptance rate, since the invention of optical fiberglass sigmoidoscope in 1969 and the introduction of 60cm fiberglass sigmoidoscope in 1976, 25cm rigidoscope has been replaced by 60cm fiberglass sigmoidoscope, and more than 80% of family physicians in the United States have been equipped with and use 60cm sigmoidoscope.
The Kaiser Permanence Multiphasic Health Checkup (MHC) in the United States randomized 10,713 people aged 35-54 years into a test and control group. Of the 5,156 people screened, 20 cases of colon cancer were detected with 60% Dukes’ A stage, and the 5-year survival rate was found to be 90% and 10-year survival rate was 80% after 16 years of follow-up; while the control group had only 48% Dukes’ A stage and 48% 10-year survival rate. The number of colon cancer deaths in the trial group was significantly smaller than in the control group (12 versus 29, respectively). However, further analysis revealed that the difference between the trial and control groups was not statistically significant when comparing only the death rate from colon cancer within the reach of sigmoidoscopy.
Lieberman et al. found that 70% to 80% of patients with polyps in the distal colon detected by fiberoptic sigmoidoscopy also had neoplasia in the proximal colon.1 A randomized controlled trial found an 80% reduction in the incidence of colon cancer in patients with polyps detected by sigmoidoscopy followed by total colonoscopy and removal of the adenomas found. Therefore, 60 cm fiberoptic colonoscopy can be used for screening not only to remove precancerous lesions within the reach of endoscopy, but also as an indication for full colonoscopy, which can reduce the incidence of all colon cancers. Experts believe that if polyps are found by sigmoidoscopy, the indications for further full colonoscopy are as follows: patients over 65 years old; villi or ≥1cm or multiple adenomas; those with family history of colon cancer.
According to the statistics of 3147 cases of colon cancer in China, 82% occurred below the splenic flexure, i.e. where 60cm colonoscopy can be reached, therefore, its application value seems to be greater than that in western countries. The Institute of Oncology of Zhejiang Medical University used 60cm fiberglass colonoscopy as a re-screening tool for sequential screening of colon cancer, and found 21 cases of colon cancer and 331 cases of polyps in 3162 high-risk people who were initially screened by 60cm colonoscopy; 11 cases of colorectal malignancy and 563 cases of polyps were detected by 60cm colonoscopy in another group of 3034 high-risk subjects. The intestinal cleanliness was satisfactory or basically satisfactory in about 95% of the cases, and there was no perforation in all 6000 cases of colonoscopy. According to our national conditions, 60 cm fiberoptic colonoscopy cannot be used as a primary screening tool, but it is worth promoting as a simple, feasible and relatively reliable re-screening or diagnostic measure.
At least two case-control studies have shown that screening with sigmoidoscopy can reduce the mortality rate of colon cancer, in Selby’s study, sigmoidoscopy was used, and in Newcomb’s study, mainly fiberoptic colonoscopy was used. The risk of dying from distal colon and rectal cancer was reduced by 70-90% in those who had more than one sigmoidoscopy than in those who had never had one.
Thiis-Evensen et al. reported that in 1983, 799 subjects from the general population in Norway were randomly divided into a sigmoidoscopy screening group and a control group. 81% of the screening group underwent sigmoidoscopy, and if polyps were found, whole colonoscopy was performed. 13 years later (1996), 451 (71%) of the two groups underwent whole colonoscopy, and it was found that there was no difference in the incidence of polyps between the screening and control groups. There was no difference in the incidence of polyps between the screening group and the control group, but the incidence of high-risk polyps (≥1 cm, with atypical hyperplasia) appeared to be lower in the screening group than in the control group (RR=0.6, 95% CI: 0.3-1.0, P=0.07), and 2 cases of colon cancer were registered in the screening group compared with 10 cases in the control group (RR=0.2, 95% CI: 0.03-0.95). However, since the overall mortality rate in the screening group was greater than that in the control group (mainly due to cardiovascular disease), it is difficult to conclude that sigmoidoscopic screening is beneficial in reducing the mortality rate of colon cancer. Two randomized controlled population trials of sigmoidoscopic screening for colon cancer are currently underway in the United Kingdom and the United States. Despite the lack of reliable evidence on the effectiveness of sigmoidoscopy for colon cancer screening, the ACS and USPSTF recommend 60-cm fiberoptic colonoscopy as one of the primary means of colon cancer screening.
(4) Total colonoscopy: There are no clinical trials to confirm the results of using total colonoscopy alone to reduce the incidence and mortality of colon cancer, but the effect of total colonoscopy, often combined with other screening tools such as FOBT or sigmoidoscopy, on reducing the incidence and mortality of colon cancer is clear. Half of the patients with progressive neoplasms (≥1 cm diameter, villous adenomas and carcinomas with atypical hyperplasia) did not have distal colon and rectal polyps, suggesting the need for total colonoscopy as a screening tool. However, colonoscopy is expensive, complicated to prepare, poorly accepted by patients, and has a certain complication rate (serious complication rate of perforation and bleeding is about 0.3%, and the morbidity and mortality rate is about 1/20,000), so the rationality of using colonoscopy alone for screening needs further verification.
(5) Double contrast air-barium enema: Although the ACS recommendation includes double contrast air-barium enema (DCBE) every 5 years as a screening tool for colon cancer, no study has proven the effectiveness of DCBE in reducing colon cancer incidence and mortality. The sensitivity of DCBE is 32% for polyps <0.5 cm, 53% for polyps 0.6-1 cm, and 48% for polyps >1 cm (including 2 cases of cancerous polyps), while the specificity of DCBE is 85%. although the sensitivity of DCBE is low, it can examine the whole colon, has a low complication rate, and is widely accepted by medical personnel and patients, so it can still be used as a screening tool for colon cancer.
(6) Other techniques: In response to the emergence of new techniques for detecting colon cancer and adenomatous polyps in recent years, the American Cancer Society Colorectal Cancer Advisory Group held a workshop in April 2002 to evaluate the effectiveness of CT colorectal imaging, immunoassay fecal occult blood test, fecal molecular markers and capsule video endoscopy in colon cancer screening. In April 2002, a workshop was held to evaluate and obtain consensus on the effectiveness of CT colorectal imaging, immunoassay fecal occult blood testing, fecal molecular markers, and capsule video endoscopy in colon cancer screening.
CT colonography, also known as virtual colonoscopy, was first introduced in 1994 and uses rapid multiple scans of spiral CT to image the internal structures of the colon in two or three dimensions, simulating the results of colonoscopy but avoiding the invasive operation of colonoscopy. According to the results of several centers in the United States, the sensitivity of CT colorectal imaging is close to 90% for polyps >1 cm, while it decreases to about 50% for those <0.5 cm, while the sensitivity for colon cancer is 100% and there are no false positives.
The colon cancer process involves multiple mutations, and mutated DNA is shed from tumor cells and their precursor cells and can be detected in the stool by PCR amplification. A new technique developed in recent years is the use of mutated DNA in stool as a molecular marker to detect colon cancer. The 61 subjects in a small sample double-blind trial included 22 colon cancers, 11 macroadenomas and 128 normal subjects. The sensitivity of fecal mutant DNA was 91% for colon cancer, 82% for adenoma, and 93% for specificity. If the K-ras mutation was excluded, the sensitivity remained the same for colon cancer, decreased to 73% for adenoma, and increased to 100% for specificity.
The advisory panel reviewed these new techniques and concluded unanimously that CT colorectal imaging and fecal mutation DNA testing are promising new techniques, but there is insufficient evidence to recommend them as screening tests, and that immunoassay occult blood testing is considered to have better sensitivity and specificity than or equal to chemical methods, while being more convenient for patients to use. For capsule video endoscopy, it is not suitable for colon cancer and polyps because it is designed to examine the upper gastrointestinal tract and small intestine.
(7) Screening protocols: The American Cancer Society (ACS) proposed guidelines for colon cancer screening in 1980, which have been revised several times, but the basic points have not changed. The American Gastroenterological Association (AGA) proposed a screening program for colon cancer risk stratification for high-risk groups (Figure 14).
(1) Given the relatively low incidence of colon cancer in China, the early age of onset, and limited health resources, the ACS protocol is difficult to implement in China. Based on previous work, Zheng Shu et al. proposed a sequential method population screening model for colon cancer (Figure 15).
A. A quantitative assessment of colon cancer risk was performed by using a questionnaire to calculate the risk of colon cancer for each subject, and AD ≥ 0.3 was used as the positive threshold; at the same time, RPHA FOBT was performed on the subjects, and the high-risk group was initially screened by these two items.
B. The high-risk group was re-screened by 60 cm fiberoptic colonoscopy.
C.Follow-up with FOBT for negative 60cm colonoscopy, and recommendation for full colonoscopy and/or air-barium dual imaging for persistent positive FOBT.
②Using this model, among 75,813 people aged 30 years or older in Jiashan County, a site with a high incidence of colon cancer, 4299 high-risk people were screened, 3162 cases (73.6%) of 60cm colonoscopy were completed, and 21 cases of colon cancer were detected, of which 62% were colon cancer and 71.4% were Dukes stage A+B. On the basis of the extension of this program, the examiner proposed a further optimized program.
A. Screening subjects ≥ 40 years old.
B, 60cm fiberoptic colonoscopy should be performed if 1 of the following is present: positive RPHA FOBT; history of colon cancer in first-degree relatives; history of previous cancer in oneself; 2 or more of the following symptoms, such as chronic constipation, mucus and blood stool, chronic diarrhea, history of intestinal polyps, chronic appendicitis, and history of mental irritation.
C. If the 60-cm colonoscopy is negative and the FOBT review is positive, a full colonoscopy or dual gas-barium imaging should be done.
Calculate the AD value of risk of colon cancer for each subject, with AD≥0.3 as the positive threshold; meanwhile, do RPHA FOBT on the subject, and use these two items to initially screen out the high-risk group.
D. The high-risk group was re-screened with 60 cm fiberoptic colonoscopy.
E. Follow up with FOBT for negative 60cm colonoscopy, and recommend whole colonoscopy and/or air-barium double imaging for persistent positive FOBT.
3.Tertiary prevention: Active treatment of clinical tumor patients to improve the quality of life and prolong the survival of patients.