Disease Overview
Colon cancer is a malignant lesion of the colonic mucosa epithelium that occurs under the action of various carcinogenic factors such as environment or genetics. It is one of the common malignant tumors, with the highest incidence rate in the age group of 40-50 years old, with about 8 million new cases each year worldwide, accounting for 10%-15% of all malignant tumors.
The incidence of colon cancer in China is on the rise. The causes are related to genetics, colonic adenoma, polyposis, chronic inflammatory lesions, low fiber and high fat diet, etc. Colon cancer starts insidiously, often has no obvious clinical manifestation in early stage, and the disease develops slowly, and most of them have reached the middle and late stage when obvious symptoms appear. Colon cancer is such a terrible killer that seriously endangers people’s health.
Pathophysiology
Colon cancer can be divided into three types: mass type (cauliflower type, soft cancer), invasive type (narrowing type, hard cancer) and ulcerated type. Among them, ulcerative type is the most common, which is usually found in the left hemicolectomy, prone to bleeding and infection, and easily penetrates the intestinal wall and metastasizes earlier. Histological typing includes
1.Adenocarcinoma: about three quarters of the cases.
2.Mucinous carcinoma: low differentiation and worse prognosis than adenocarcinoma.
3.Undifferentiated carcinoma: very low differentiation and the worst prognosis. Clinical stages include: Dukes A stage: cancer is confined to the intestinal wall; Dukes B stage: cancer invades outside the intestinal wall; Dukes C stage: with lymph gland metastasis; Dukes D stage: distant metastasis or extensive invasion of adjacent organs cannot be removed.
The ways of colon cancer metastasis include.
1.Direct infiltration: Generally, there is circular infiltration along the transverse axis of intestinal tube, and it develops deeper into the intestinal wall, while it spreads up and down along the longitudinal axis more slowly. After the cancer invades the plasma membrane, it often adheres to the surrounding tissues, adjacent organs and peritoneum.
2.Lymphatic metastasis: it is the main metastasis mode of colon cancer. Generally, it spreads from near to far, but there are also cross metastases in different order. The chance of lymphatic metastasis increases after the cancer invades the muscle layer of intestinal wall, and the chance of lymphatic metastasis is even greater if the subplasma lymphatic vessels are invaded.
3.Hematogenous metastasis Generally, cancer cells or cancer emboli reach the liver first along the portal vein system, and then other tissues and organs such as lung, brain and bone.
4.Peritoneal implantation metastasis: cancer cells shed in the intestinal cavity may be planted on other mucosa, and shed in the peritoneal cavity may be planted on the peritoneum.
Pathogenesis mechanism
Although the exact pathogenesis of colorectal cancer has not yet been fully elucidated, further research on the pathogenesis of tumor has raised the theory of physical, chemical, viral and mutational carcinogenesis to a multi-step and multi-factor theory of comprehensive carcinogenesis. At present, people have gradually accepted the view that the occurrence of colorectal cancer is a gradual process involving the activation of multiple oncogenes and inactivation of oncogenes. From the epidemiological point of view, the development of colon cancer is related to genetics, environment, living habits, especially diet.
1.Environmental factors: It has been proved that among various environmental factors, dietary factors are the most important, and the incidence of colon cancer is positively related to high fat consumption in food. In addition, it may also be related to the lack of trace elements and change of living habits.
2. Genetic factors: If a person’s first-degree relative, such as a parent, has had colon cancer, his risk of developing the disease is 8 times higher than normal people. About 1/4 of new cases have a family history of colon cancer. Familial polyposis is an autosomal dominant disease with a prevalence of up to 50% in the family, and if left untreated, there is a possibility of colon cancer after the age of 10.
3, colorectal adenoma: autopsy material research found that the incidence of colorectal adenoma is basically the same as colorectal cancer. According to statistics, the incidence of colorectal cancer is 5 times higher in patients with single adenoma than in those without adenoma, and 1 times higher in those with multiple adenoma than in those with single adenoma. Choroidal adenoma-like polyps are prone to develop into cancer, with a malignancy rate of about 25%, and tubular adenoma-like polyps have a malignancy rate of 1-5%.
4.Chronic inflammation of the colon: It is reported that the prevalence of intestinal cancer is positively correlated with the endemic area of schistosomiasis, and it is generally believed that some of the inflammatory changes in the intestine due to schistosomiasis will become cancerous. Other chronic inflammatory diseases of the intestine also have the possibility of cancer, such as the risk of colon cancer in patients with Crohn’s disease or ulcerative colitis is 30 times higher than that of normal people.
Clinical manifestations
1.Early symptoms: In the earliest stage, there may be abdominal distension, discomfort and indigestion-like symptoms, among which in the case of right hemi-colon cancer, it is mostly abdominal pain and discomfort or hidden pain. The symptoms of early colon cancer can be intermittent at the beginning, and then turn into continuous. The change of stool habit is also one of the symptoms of early colon cancer. When the right half colon cancer is manifested as early thin stool with pus and blood and increased number of bowel movements, alternating diarrhea and constipation may occur when the cancer of colon cancer continues to increase and affects the passage of stool, while the left half colon cancer is mostly manifested as difficulty in defecation, which will continue to worsen with the development of colon cancer.
2.Abdominal mass: It is a mass infiltrated by tumor or omentum and surrounding tissues, with hard texture and irregular shape, and some of them can have certain mobility with intestinal tube; in advanced stage, the tumor infiltration is serious and the mass can be fixed.
3.Intestinal obstruction manifestation: incomplete or complete low level intestinal obstruction symptoms, such as abdominal distension, abdominal pain, constipation or stool closure. The common symptoms of colon tumor are abdominal bulge, intestinal shape, local pressure pain, and hyperactive bowel sounds. The lumen of the left half of the colon is relatively small, and the stool is already sticky and shaped by this point, and the part is mostly invasive cancer, and the intestinal lumen is narrowed in a circular manner, so the symptoms of intestinal obstruction appear earlier.
4.Toxic symptoms: It is also one of the clinical manifestations of colon cancer. Due to the blood loss and toxin absorption of colon cancer tumor ulceration, it often leads to anemia, low fever, weakness, emaciation, swelling and other symptoms of colon cancer patients, especially anemia and emaciation. The right hemicolectomy is rich in blood and lymph, with strong absorption ability, and the cancer is mostly soft, easy to ulcerate and necrosis, resulting in bleeding and infection, so the symptoms are mainly toxic.
5.Late symptoms: jaundice, ascites, swelling and other signs of liver metastasis, as well as cachexia, rectal anterior concave mass, enlarged supraclavicular lymph nodes and other signs of distant tumor spread and metastasis.
Diagnosis and differentiation
The early symptoms of colon cancer are not noticed by patients and are often treated as “dysentery” and “enteritis” when they seek medical treatment, but once symptoms of poisoning or obstruction appear and abdominal masses are touched, it is not early stage. Therefore, if a patient develops persistent diarrhea or constipation without any specific cause; develops frequent stools, stools with pus, mucus or blood; or develops persistent abdominal pain, flatulence and abdominal discomfort, and the general treatment is ineffective, further examination should be performed.
Auxiliary examination
The examination and diagnosis methods of colon cancer are mainly as follows.
1.X-ray examination: including whole gastrointestinal barium meal examination and barium enema examination. It can observe the whole picture of colon form, whether there are multiple polyps and multiple cancer foci, and provide the basis for the surgical treatment of colon tumor patients. The lesion signs may initially appear as stiffness of the intestinal wall and mucosal destruction, followed by a constant filling defect and narrowing of the intestinal lumen. The effect of gas-barium double contrast imaging is better.
2, endoscopy: where there is blood in the stool or stool habit changes, rectal finger examination without abnormal findings, should routinely perform fiber colonoscopy. It can not only detect various types of lesions in the colon, but also take tissue biopsy to make a clear diagnosis so as to avoid missing or misdiagnosis.
3.Serum carcinoembryonic antigen (CEA) examination: it is not specific for detecting and diagnosing colon cancer, and the increase of value is often related to the increase of tumor, which can be restored to normal value after complete resection of colon tumor and can be increased several weeks before recurrence, so it is helpful for estimating the prognosis, monitoring the efficacy of treatment and recurrence.
4.B-type ultrasound scan, CT or MRI examination: they can not directly diagnose colon cancer, but they have some value in determining the location, size and relationship between cancer and surrounding tissues, lymphatic and liver metastasis. It is mainly used to understand the extent of tumor infiltration into the intestinal canal and whether there are local lymph nodes or distant organ metastases. It can be used for preoperative staging and postoperative review.
5.Fecal examination: By detecting tumor M2 pyruvate kinase (M2-PK) in feces, it is found that the M2-PK value of colon cancer patients is 14 times higher than that of normal people. Therefore, fecal tumor M2-PK detection provides a promising new means for colon cancer screening.
Differential diagnosis
1.Benign colon mass: longer duration, milder symptoms, X-ray shows local filling defect, regular morphology, smooth surface, sharp edges, no narrowing of the intestinal lumen, and intact uninvolved colonic pouch.
2, inflammatory diseases of the colon (including tuberculosis, schistosomiasis granuloma, ulcerative colitis, dysentery, etc.): the history of inflammatory intestinal lesions have their own characteristics, stool microscopy may have their special findings, such as eggs, phagocytosis, dysentery can be cultured pathogenic bacteria. x-ray lesions involved in the intestinal canal longer, while cancer is rarely more than 10 cm. colonoscopy and pathological histological examination can further confirm the diagnosis.
3.Colonic spasm: X-ray examination is a small segment of intestinal lumen narrowing, which is reproducible.
4.Appendiceal abscess: there is an abdominal mass, but the mass is located outside the cecum on X-ray, and the patient has a history of appendicitis.
Disease treatment
The principle of colon cancer treatment is comprehensive treatment mainly based on surgical resection, while combined with chemotherapy and radiotherapy to reduce the recurrence rate after surgery and improve the survival rate. For unresectable colon cancer, neoadjuvant chemotherapy can be adopted, which on one hand can reduce the stage of tumor and transform part of unresectable tumor into resectable tumor; on the other hand can prolong the survival time of patients and improve their survival quality. The main treatment methods for colon cancer are listed as follows.
Surgical treatment
The scope of radical colon cancer surgery includes the intestinal collaterals where the cancer is located and its entire colon mesentery (complete mesocolic excision, CME). In other words, the cancer itself is removed, and the regional lymph nodes that may have metastasized can be completely removed. Therefore, it is possible to cure colon cancer only after a thorough surgery.
In addition, patients with liver or lung metastases are not completely lost to treatment. The new view is that if the metastatic lesions can be removed at the same time, they are removed together with the lesions of colon cancer, and if the metastatic lesions cannot be removed first with neoadjuvant chemotherapy and then removed after the descending stage. In some patients with liver metastases, the metastases are limited to one lobe or one segment, and surgical resection is not only simple, but also has a 5-year survival rate of 50%. The choice of surgical indication and the surgeon’s experience are the key factors in deciding the surgery.
Lung is the most common site of extrahepatic metastasis in colon cancer, with an incidence of 10%-25%, and if left untreated, its average survival time is no more than 10 months. With the accumulation of experience in surgical treatment, more surgical experts believe that as long as the lung metastases can be completely resected, surgery is recommended even if the metastases are multiple. The 5-year survival rate of surgical treatment can reach 22.0% to 48.0%.
Chemotherapy
Colon cancer gradually metastasizes to distant sites with growth and development, and 3/4 of patients already have metastases at the time of diagnosis, and half of those who can undergo radical surgical resection eventually develop distant metastases. Therefore, chemotherapy after radical surgery, i.e. adjuvant chemotherapy, is an important part of the comprehensive treatment of colon cancer. The mechanism of adjuvant chemotherapy is to control and destroy the residual lesions in the body after radical surgery with chemotherapy. As the tumor load of the body is reduced after surgery, the proliferation of distant micro-metastases leads to its increased sensitivity to chemotherapy, and early chemotherapy after surgery can achieve the maximum purpose of tumor elimination.
Radiotherapy
For unresectable tumors or distant metastases, local radiotherapy is also one of the common treatment methods for advanced colon cancer, which can shrink the tumor and improve the patient’s symptoms, and is often used in combination with other treatment options. At present, the most researched and effective treatment is the combination of surgery and radiation, including preoperative radiation, intraoperative radiation, postoperative radiation and “sandwich” radiotherapy.
However, radiotherapy is harmful to the body and should be used with caution for advanced colon cancer patients with poor physical function, and must prevent the damage of human immune function caused by toxic side effects.
Biological therapy
Immunotherapy and gene therapy are both biological therapies, and immunotherapy is more commonly used in clinical practice. The main purpose is to mobilize the body’s natural anti-cancer ability and restore the balance of the body’s internal environment, which is equivalent to the Chinese medicine practice of “supporting and cultivating the root and harmonizing yin and yang”. Biological therapy can prevent the recurrence and metastasis of tumors, improve the efficacy of radiotherapy and chemotherapy, and reduce the toxic side effects of radiotherapy and radiotherapy.
Targeted Therapy
The so-called molecular targeted therapy is to design the corresponding therapeutic drugs at the cellular molecular level, targeting the defined oncogenic site (the site can be a protein molecule or a gene fragment inside the tumor cell). Molecular targeted therapy is also known as “biological missile”.
In 2010, the American Society of Clinical Oncology (ASCO) reported that molecularly targeted therapies in colon cancer have brought many encouraging results, such as the combination of monoclonal antibodies and chemotherapy can extend the average survival of patients by about 24 months.
However, research on targeted therapies is just in its infancy, and the predictors of targeted therapies are still unclear, which means that it is difficult to predict whether patients will benefit from the treatment before we administer the drugs. Although the efficacy of some targeted drugs in the treatment of advanced colon cancer has been recognized, the timing and application of these drugs are still highly controversial. With the widespread use of targeted drugs, the problem of drug resistance has become increasingly prominent. Currently, the drug treatment of colon cancer is in the era of transition from pure cytotoxic therapy to molecular targeted therapy. There is still a long way to go in the research of targeted therapy for colon cancer.
Chinese medicine treatment
At present, most of them are combined with surgery or chemotherapy for comprehensive treatment. It can reduce the side effects of chemotherapy and enhance the body’s resistance to disease. According to the patient’s specific conditions, the treatment is based on dialectical evidence. The principle of treatment is to clear heat and detoxify, dispel stasis and disperse nodules, and to attack if there is solidity, and to supplement if there is deficiency.
Therefore, the treatment principle of colon cancer is a comprehensive treatment mainly based on surgery. The purpose of treatment is to prolong life and improve survival quality.
Prognosis of disease
The overall five-year survival rate after radical surgery can reach more than 50%, and the five-year survival rate of early stage patients can reach more than 80%, but only about 30% for late stage.
The factors affecting the prognosis of colon cancer are the following two aspects.
1. Clinical factors.
(1) Age: The prognosis of young colorectal cancer patients is poorer, while the differentiation of tumors is poorer in young patients, among which there are more mucinous adenocarcinomas.
(2) Biological performance of tumor: tumor diameter, infiltration and fixation of tumor and degree of invasion can affect the prognosis.
(3) Clinical stage: late stage of disease has poor prognosis.
2.Biological characteristics.
(1) Blood carcinoembryonic antigen (CEA) concentration: the possibility of recurrence of colon cancer is related to the preoperative CEA concentration, which is inversely proportional to the degree of tumor differentiation; the higher the CEA concentration, the lower the degree of tumor differentiation, and the more likely the tumor will recur.
(2) Ploidy and chromosome of tumor: the malignancy degree of cancer cells depends on different degrees of changes in DNA content, ploidy composition, proliferation and chromosomal aberrations of cancer cells.
Disease prevention
The World Health Organization has proposed a 16-word policy for colon cancer prevention, namely, “reasonable diet, moderate exercise, smoking cessation and alcohol restriction, and psychological balance”. Specific measures include the following.
1.Regular checkups: People with high risk of colon cancer, such as men over 40 years old, patients with familial polyps, ulcerative colitis patients, chronic schistosomiasis patients and people with family history of colon cancer should have regular checkups to be alert to the signals and early symptoms of colon cancer, such as change in stool habit, alternating diarrhea and constipation, blood in stool or black stool, flattening and thinning of stool shape, etc.
2.Improve dietary habits: change the habit of eating meat and high-protein food as the main food. Eat less high-fat food, especially to control the intake of animal fat. Reasonable arrangement of daily diet, eat more fresh fruits, vegetables and other foods rich in carbohydrates and coarse fibers, and appropriately increase the proportion of coarse grains and grains in the main diet, not too fine and too fine.
3, prevention and control of intestinal diseases: actively prevent various polyps, chronic enteritis (including ulcerative colitis), schistosomiasis, chronic dysentery, etc., for intestinal polyps should be dealt with early. Colon polyps are divided into five categories, namely adenomatous polyps, inflammatory polyps, misshapen polyps, biochemical polyps and mucosal hypertrophy redundancy, etc. Among them, adenomatous polyps are true neoplastic polyps, which are precancerous lesions of colon cancer, so when colonic adenomas are found, they should be removed at the benign adenoma stage and pathological examination. If not treated early, most of them will become colorectal cancer. In addition, habitual constipation should be actively treated and attention should be paid to keep the bowels open.
4.Chemical drug prevention: At present, the main drugs used for colon cancer prevention are:
(1) Antioxidants: The mechanism of action is to protect DNA from free radical damage, including vitamins C and E, β2 carotene, folic acid and so on. In a study lasting 8 years, the incidence of colorectal cancer was reduced by 16% in male smokers aged 50-69 years in the vitamin E group compared with the placebo control group.
(2) Non-steroidal anti-inflammatory drugs: These drugs have been shown to inhibit the development of colon cancer. Some studies have shown that aspirin and NSAIDs have the effect of reducing the incidence of colon cancer. Subjects who regularly take aspirin or NSAIDs (at least 16 days per month, more than 3 months per year) have a 50% lower risk of developing colon cancer and a 40% lower risk of dying from colon cancer.
(3) Other related drugs being studied include: peroxisome proliferator-activated receptor ligands, dimethyl sulfoxide (DFMO), calcium (conjugated bile acid), vitamin D, epidermal growth factor receptor inhibitors, tyrosine kinase inhibitors, vascular endothelial growth factor inhibitors, matrix metalloproteinase inhibitors, etc.
5, active exercise: find a suitable exercise for yourself, enhance physical fitness, improve immunity, self-relaxation, relieve stress and maintain a good state of mind.
Diet attention
Research proves that high fat diet can promote the occurrence of intestinal tumors. Studies of different immigrant populations in the United States have shown that the incidence of colon cancer is lower among native Asian Chinese, while the incidence of colon cancer is higher among the descendants of Chinese born in the United States. Fat intake is positively associated with colon cancer incidence, but the role of different types of fat on colon cancer incidence is completely different. Saturated fats of animal origin are most strongly associated with colon cancer incidence. Vegetable oils are not associated with colon cancer incidence, while fish oil, which is rich in unsaturated fatty acids, has a preventive effect on colon cancer. Therefore, the daily diet should be reasonably arranged, with more fresh fruits and vegetables and other foods rich in carbohydrates and coarse fibers, and the proportion of coarse and mixed grains in the main food should be increased appropriately, not too fine and too refined.
High-fat, high-protein and low-fiber diets produce more carcinogenic substances and act on the colon for a long time, which will certainly lead to an increase in the incidence of colon cancer. Therefore, eat less or no food rich in saturated fat and cholesterol, including: lard, beef fat, fatty meat, animal offal, fish roe, etc. Limit vegetable oil to about 20-30 grams per person per day (about 2-3 tablespoons). Eat no or less fried foods. Moderate consumption of foods containing unsaturated fatty acids, such as olive oil, tuna, etc. Take 35 grams or more of dietary fiber daily. Eat more foods rich in dietary fiber: konjac, soybeans and their products, fresh vegetables and fruits, seaweeds, etc. Replace fine grains with some coarse grains. Eat more fresh vegetables and fruits to replenish carotene and vitamin C. Eat walnuts, peanuts, dairy products, seafood, etc. in appropriate amount to replenish vitamin E. Pay attention to the intake of foods rich in trace elements of selenium, such as malt, fish and mushrooms.
Bowel cancer patients are forbidden to eat spicy food. Foods such as chili and pepper have stimulating effect on the anus and must not be eaten. After colon cancer surgery, patients should pay attention to strengthen care and diet nutrition after surgery to promote patients’ body recovery. In the initial stage when they cannot eat normally, intravenous rehydration should be the main focus. After being able to eat, the diet should start with liquid food, gradually transition to semi-liquid food and soft food, and then increase other diets after the gastrointestinal tract gradually adapts. Care should be taken not to eat too much fat, a reasonable mix of sugar, fat, protein, minerals, vitamins and other foods, every day there should be cereals, lean meat, fish, eggs, milk, all kinds of vegetables and soy products, the amount of each should not be too much. This will replenish the various nutrients required by the body.
Expert opinion
1.The early diagnosis rate of colon cancer in China is low: there is a big gap between the diagnosis rate of early colon cancer in China and developed countries such as Europe and America. The rate of stage I colon cancer in foreign countries is about 25%, while the rate of stage I colon cancer in China is generally less than 10%. The reasons for the low rate of early tumor diagnosis in China include.
(1) Patients do not have the habit of physical examination and cannot seek timely diagnosis;
(2) The medical conditions in China are poor, and the necessary screening and key screening cannot be conducted for the majority of middle and old age groups.
2. Comprehensive treatment mainly based on surgery: Surgery is still the most important tumor treatment, and the technology and standardization of surgical resection is the basis of efficacy. The technology of surgery is still developing, and the new radical surgery for colon cancer should follow the concept of tumor-free, sterile, bloodless and minimally invasive total colon mesenteric resection. It is difficult to rely on surgery alone for middle and late stage colon cancer, and further improve the survival with chemotherapy, radiotherapy, immunotherapy, biotherapy and other comprehensive treatments.
3. Early stage colon cancer can be treated without chemotherapy after surgery: the 5-year survival rate of stage I colon cancer is 90-95%, and chemotherapy has little improvement on survival rate, while the side effects of chemotherapy and treatment cost make patients bear a great burden. Therefore, it is generally believed that adjuvant chemotherapy is unnecessary for stage I colon cancer.
Postoperative adjuvant chemotherapy for stage II colon cancer is controversial. Stage II patients with high-risk factors may benefit from adjuvant therapy.
Specific high-risk factors include.
(1) tumor that has penetrated the plasma membrane layer.
(2) hypodifferentiated tumors (tumor differentiation grade 3 to 4).
(3) infiltration of lymphatic vessels, blood vessels and nerves;
(4) Positive or suspicious surgical margins;
(5) Combined intestinal obstruction or intestinal perforation;
(6) Postoperative pathological examination returned 12 lymph nodes detection.
Adjuvant chemotherapy after surgery for stage III colon cancer is internationally recognized. The survival rate of patients can be significantly improved.
4.Individualized treatment of tumor: individualized treatment is a treatment plan designed according to the patient’s individual situation, which has the advantage of tailor-made, maximally adapting to the patient’s situation, and is the development direction of comprehensive tumor treatment. Individualized treatment is guided by standardized treatment, i.e. within the scope of the National Comprehensive Cancer Network (NCCN) guidelines. Otherwise it is liberalization.