Colon cancer is a malignant lesion of the colonic mucosal epithelium occurring under the action of various carcinogenic factors such as environment or genetics. The causes are related to genetics, colonic adenoma, polyposis, chronic inflammatory lesions, low fiber and high fat diet. Colon cancer is insidious, often has no obvious clinical manifestation in early stage, and the disease develops slowly, and most of them have already reached the middle and late stage when obvious symptoms appear, and the mortality rate is second only to lung cancer and liver cancer, accounting for the third place of malignant tumor in China.
I. Etiology and Pathogenesis
Morphologically, we can see various stages of hyperplasia, adenoma and carcinoma, as well as the corresponding chromosomal changes. With the development of molecular biology technology, the simultaneous existence of molecular events and gene expression is gradually recognized, from which it is clear that the development of cancer is a multi-step, multi-stage and multi-gene involved cytogenetic disease.
During this process, genetic mutations include oncogene activation (K-ras, c-myc, EGFR), oncogene inactivation (APC, DCC, P53), mismatch repair gene mutations (HMSHI, HLHl, PMSl, PMS2, GTBP) and gene over-expression (COX-2). Inactivation of the APC gene leads to heterozygous deletion, and the initiation of the APC/β-catenin pathway contributes to the adenoma process; mismatch repair gene mutations lead to genetic instability and hereditary non-polyposis colon cancer (HNPCC) syndrome.
Although the cause of colon cancer is not clear, its associated risk factors are gradually recognized, such as excessive animal fat and animal protein diet, lack of fresh vegetables and fibrous foods; lack of moderate physical activity. Genetic susceptibility also has an important position in the development of colon cancer, such as family members carrying mismatch repair gene mutations in hereditary non-polyposis colon cancer, which should be considered as a group of high-risk groups for colon cancer. Some diseases, such as familial intestinal polyposis, have been recognized as pre-cancerous diseases; colonic adenoma, ulcerative colitis, and colonic schistosomiasis granuloma, are more closely related to the occurrence of colon cancer.
II. Pathology
Pathology and typing can be distinguished according to the general shape of tumor:
1.Mass-type tumor grows into the intestinal cavity, which is usually found in the right colon, especially the cecum.
2.Infiltrating type is infiltrating along the intestinal wall, easily causing intestinal lumen narrowing and intestinal obstruction, mostly occurring in the left colon.
3.Ulcerated type is characterized by deep growth to the intestinal wall and infiltration to the surrounding, which is a common type of colon cancer.
Microscopic histological classification is more common for:
1.Adenocarcinoma: accounts for most of colon cancer.
2.Mucinous carcinoma: prognosis is worse than adenocarcinoma.
3.Undifferentiated carcinoma: easily invades small blood vessels and lymphatic vessels, and has the worst prognosis.
Clinicopathological staging: The purpose of staging is to understand the process of tumor development, guide the formulation of treatment plan and estimate the prognosis. The modified Dukes staging and the TNM staging proposed by UICC are still used internationally.
According to the supplement of Dukes method in China, it is divided into: Dukes A stage when the cancer is confined to the intestinal wall. Stage B for those who penetrate the intestinal wall and invade into the plasma membrane or/and outside the plasma membrane, but without lymph node metastasis. Those with lymph node metastasis are classified as stage C. Among them, those with lymph node metastasis limited to the vicinity of cancer such as colon wall and paracolon lymph nodes are classified as stage C1; those with metastasis to the lymph nodes of the mesentery and root of the mesentery are classified as stage C:. Those with distant metastasis or abdominal metastasis, or those with extensive invasion of adjacent organs that cannot be resected are considered stage D.
TNM staging method:
T stands for primary tumor, and Tx is the inability to estimate the primary tumor. T0 for no evidence of primary tumor; Tis for carcinoma in situ; T1 for tumor invading the myxomucosal and submucosal layers; T2 for invading the intrinsic muscular layer; T3 for penetrating the muscular layer to the subplasma; T4 for penetrating the dirty peritoneum or invading other organs or tissues.
N is regional lymph nodes, and Nx cannot be estimated for lymph nodes; No for no lymph node metastasis; N1 for 1-3 regional lymph nodes with metastasis; N2 for 4 or more regional lymph nodes.
M is distant metastasis, Mx for inability to estimate distant metastasis; M0 for no distant metastasis; M1 for any distant metastasis.
Colon cancer mainly metastasizes via lymph, first to the colon wall and paracolon lymph nodes, then to the lymph nodes around the mesenteric vessels and the root of mesenteric vessels. Hematogenous metastasis is mostly seen in liver, followed by lung and bone. Colon cancer can also directly infiltrate into adjacent organs. For example, sigmoid colon cancer often invades the bladder, uterus and ureter. Transverse colon cancer can invade the stomach wall and even form internal fistula. The shed cancer cells can also be planted and metastasized in the peritoneum.
Clinical manifestations
There are no special symptoms in the early stage of colon cancer, but the following symptoms are mainly found after the development:
1.Change of defecation habit and stool trait: it is often the earliest symptom. Most of them are increased number of bowel movements, diarrhea, constipation, blood, pus or mucus in stool.
2, abdominal pain: is also one of the early symptoms, often persistent hidden pain with inaccurate positioning, or only abdominal discomfort or bloating feeling, when there is intestinal obstruction, the abdominal pain is aggravated or paroxysmal colic.
3. Abdominal mass: Most of them are the tumor itself, sometimes they may be the accumulation of feces in the intestinal cavity near the obstruction. Most of the masses are hard and nodular in shape. If it is transverse colon and sigmoid colon cancer, it may have a certain degree of activity. If the cancer penetrates and is complicated by infection, the mass is fixed and may have obvious pressure pain.
4.Symptoms of intestinal obstruction: Generally speaking, it is a symptom of the middle and late stage of colon cancer, mostly manifested as chronic low-level incomplete intestinal obstruction, mainly manifested as abdominal distension and constipation. Abdominal distension and pain or paroxysmal colic. When complete obstruction occurs, the symptoms are aggravated. Left-sided colorectal cancer can sometimes have acute complete colon obstruction as the first symptom.
5. Systemic symptoms: due to chronic blood loss, cancer ulceration, infection, toxin absorption, etc., patients may appear anemia, emaciation, weakness, low fever, etc. In the late stage of disease, liver enlargement, xanthogranuloma, swelling, ascites, rectal anterior concave mass, supraclavicular lymph node enlargement and cachexia may appear.
Due to the different pathological types and locations of cancer, the clinical manifestations are also different. Generally, right-sided colon cancer is mainly manifested by systemic symptoms, anemia and abdominal mass, while left-sided colon cancer is significantly manifested by symptoms such as intestinal obstruction, constipation, diarrhea and blood in stool.
IV. Examination
1.Anal tube diagnosis and proctoscopy: check whether there are rectal polyps, rectal cancer, internal hemorrhoids or other lesions.
2.Sigmoidoscopy and fiberoptic colonoscopy: Microscopy can detect cancer and observe its size, location and local infiltration range.
3.Abdominal plain film: Applicable to cases of acute intestinal obstruction, with inflation and distension of the colon above the obstruction site.
4.Barium enema: It can be seen that the intestinal wall of the cancer site is stiff, poorly dilated, peristalsis is weakened or disappeared, irregular shape or disappearance of colonic pouch, narrowing of intestinal lumen, disorder, destruction or disappearance of mucosal folds, filling defect, etc. Barium air double contrast imaging is more helpful for the diagnosis of tumors with tissues in the colon.
5. Carcinoembryonic antigen (CEA): It has little diagnostic value for early tumor, but it is helpful to speculate the prognosis and judge the recurrence.
V. Diagnosis
Early symptoms of colon cancer are not obvious and can be easily ignored. Anyone above 40 years old with any of the following symptoms should be classified as high-risk group:
1.History of colorectal cancer in relatives of grade I; 2.History of cancer or history of intestinal adenoma or polyp; 3.Positive fecal occult blood test; 4.With two or more of the following five manifestations: mucus blood stool, chronic diarrhea, chronic constipation, history of chronic appendicitis and history of mental trauma. B-mode ultrasound and CT scan are useful for understanding abdominal masses and enlarged lymph nodes, and for detecting metastases in the liver. Serum carcinoembryonic antigen (CEA) value is higher than normal in about 60 colon cancer patients, but the specificity is not high. It is helpful to judge the prognosis and recurrence after surgery.
VI. Treatment
It is a comprehensive treatment mainly based on surgical resection.
The scope of radical surgical resection of colon cancer must include the intestinal mix where the cancer is located, its mesentery and regional lymph nodes.
1.Right hemicolectomy: it is applicable to the cancer of cecum, ascending colon and hepatic flexure of colon. For cancer of cecum and ascending colon, the scope of resection includes the right half of transverse colon, ascending colon and cecum, including the end segment of ileum which is about 15-20 cm long, and end-to-end or end-to-side anastomosis of ileum and transverse colon. For carcinoma of the hepatic flexure of the colon, in addition to the above-mentioned scope, the lymph nodes of the transverse colon and the right artery group of the gastric omentum must be removed.
2.Transverse colectomy:It is applicable to transverse colon cancer. The entire transverse colon including the hepatic or splenic flexure and the lymph nodes of the gastrocolic ligament are removed, and end-to-end anastomosis of the ascending and descending colon is performed. If the anastomosis cannot be performed due to high tension at both ends, for transverse colon cancer on the left side, the descending colon can be removed and an anastomosis of ascending colon and sigmoid colon can be performed.
3.Left hemicolectomy: It is applicable to colonic splenic flexure and descending colon cancer. The scope of resection includes the left half of transverse colon and descending colon, and part or all of sigmoid colon can be removed according to the height of descending colon cancer, and then intercolonic or end-to-end anastomosis between colon and rectum can be performed.
4.Radical resection of sigmoid colon cancer: according to the length of sigmoid colon and the location of cancer, the whole sigmoid colon and all descending colon, or the whole sigmoid colon, part of descending colon and part of rectum should be resected and colorectal anastomosis should be performed respectively.
Surgery for colon cancer complicated with acute intestinal obstruction should be performed early after proper preparation such as gastrointestinal decompression, correction of water and electrolyte disorders and acid-base imbalance. For right-sided colon cancer, right hemicolectomy and ileocolic anastomosis should be performed. If the patient’s condition does not allow, cecum stoma can be made first to release the obstruction, and radical resection can be performed in the second stage of surgery. If the cancer cannot be resected, the terminal ileum can be cut off, the proximal end of the ileum can be anastomosed with transverse colon, and the distal end of the ileum can be stomaed. If left-sided colon cancer is complicated by acute intestinal obstruction, transverse colostomy should be made on the proximal side of the obstruction site, and then radical resection should be performed in the second stage of surgery under the condition of adequate intestinal preparation. For those whose tumors cannot be resected, palliative colostomy should be performed.
In the specific operation of surgical resection of colon cancer, firstly, the distal and proximal ends of the intestinal canal where the tumor is located should be tied with gauze strips to prevent cancer cells from spreading and planting in the intestinal lumen. The corresponding blood vessels are then ligated to prevent cancer cells from metastasizing in the bloodstream. Dilute anti-cancer chemicals such as 5-FU can be given in the ligated intestinal cavity, and then the intestine can be removed.
Colon cancer surgery generally requires adequate intestinal preparation, which mainly includes bowel evacuation and application of appropriate amount of intestinal antibiotics. There are several methods of intestinal evacuation, such as oral administration of 2000-3000 ml of compound polyethylene glycol electrolyte 12-24 hours before surgery, or oral administration of mannitol. There are also oral laxatives, such as magnesium sulfate or senna leaf solution, given one day before surgery. Unless intestinal obstruction is suspected, the intestinal cleansing method of repeated cleansing enemas is less commonly used in clinical practice. ②The use of intestinal antibiotics:Routine use of metronidazole 0,4g three times a day; neomycin 1,0g twice a day, one day before surgery. Three-day method of intestinal preparation is not recommended.
Chemotherapy.
The prognosis of colon cancer is good, and the 5-year survival rates of Dukes stages A, B and C are about 80%, 65% and 30%, respectively, after radical surgical treatment.
Chemoprevention: Colorectal cancer offers the possibility of prevention because of the long evolutionary sequence of polyp, adenoma and adenocarcinoma. The commonly used substances to block the evolution are non-street anti-inflammatory drugs (NSAIDs), which can antagonize cyclooxygenase activity and inhibit nuclear factor kappaB, such as aspirin, which has been reported in clinical trials, sulindac, which has reversible reduction and irreversible oxidation to inhibit prostaglandin products leading to polyp regression, and vitamins E, C, and A, which can inhibit epithelial proliferation of rectal adenomas. Calcium, soybeans, and vegetables are all beneficial dietary and health foods that have protective effects.