colorectal cancer



Overview of Malignant Tumors

Definition

The intestinal tract is an important digestive organ of the human body, referring to the digestive tube from the beginning of the duodenum up to the anal canal, which is the longest section of the digestive tube, including the small intestine and the large intestine.

The large intestine is divided into appendix, appendix, colon, rectum and anal canal.

Bowel cancer broadly refers to all malignant tumors occurring in the human bowel [1].

Staging and classification

Classification according to site

Colorectal cancer

Colorectal cancer, which mainly includes colon cancer and rectal cancer, is a malignant tumor of epithelial origin of the large intestine.

Among them, colon cancer is subdivided into left hemi-colon cancer and right hemi-colon cancer, which have incompletely consistent clinical features and prognosis.

Small Bowel Cancer

Broadly speaking, small bowel cancer refers to malignant tumors occurring in the small bowel, including carcinoma of epithelial origin of the small bowel, sarcoma of mesenchymal origin, etc., and there are as many as 40 pathological types, with adenocarcinoma, carcinoid tumor, lymphoma, sarcoma, and malignant mesenchymal stromal tumor being the most common ones.

In the narrow sense, small bowel cancer refers to malignant tumors originated from the epithelium of small bowel, including duodenal cancer, jejunum cancer and ileum cancer. Unless otherwise specified, the term small bowel cancer in this article refers to small bowel cancer in the narrow sense.

Gross staging

Gross staging refers to the morphology directly seen by naked eyes, colorectal cancer can be categorized into the following three types.

Bulging type

The tumor is in the form of nodule, polyp, cauliflower or mushroom.

It mostly occurs in the right half of colon and rectal pot belly.

It has low invasiveness and better prognosis.

Ulcer type

According to the shape and growth of the ulcer, it can be divided into limited ulcer type and infiltrative ulcer type.

Ulcerative type is the most common, accounting for more than half of colorectal cancer.

It has high malignancy and early lymph node metastasis.

Invasive type

Tumor diffusely infiltrates into all layers of the intestinal wall, thickening the local intestinal wall, but there is often no obvious ulcer or elevation on the surface.

This type is most common in the sigmoid colon and upper rectum, with high malignancy and early metastasis.

Morbidity

Colorectal cancer

The incidence of colorectal cancer is higher in men than in women [2].

The incidence rate of colorectal cancer in China increases significantly from the age of 50, reaches a peak at the age of 75-80, and then decreases slowly. However, colorectal cancer is not uncommon in young people under 30 years of age [2].

The common histologic types (pathological types) of colorectal cancer are adenocarcinoma, adenosquamous carcinoma, squamous cell carcinoma, and undifferentiated carcinoma, among which adenocarcinoma is the most common [2].

Small bowel cancer

Small bowel cancer is relatively rare, with an incidence rate of approximately 2% of all malignant tumors of the gastrointestinal tract, an average age of onset of 65 years, and is usually more common in males than in females, with a male-to-female ratio of approximately 3:2 [1].

Adenocarcinoma accounts for 30%-50% of the pathological types of small bowel cancer, carcinoid tumor accounts for 25%-30%, and lymphoma and malignant mesenchymal tumor each accounts for about 15% [1].

Causes

Causes

The etiology of bowel cancer is still not fully understood, and the following factors may increase the incidence.

Dietary factors

It is generally accepted that a long-term diet high in animal protein, fat and fiber is a high risk factor for colorectal cancer.

A high fiber diet may reduce the risk of bowel cancer.

Lifestyle

Bad lifestyle habits such as smoking and drinking alcohol can increase the risk of bowel cancer.

Lack of physical activity, sedentary occupations, overweight and obesity, and poor bowel habits are all risk factors for bowel cancer.

Related Diseases

Chronic ulcerative colitis, polyposis, and adenomas all have a probability of developing cancer.

The risk of colorectal cancer in patients with Crohn’s disease is 4 to 20 times higher than that in the normal population.

Familial adenomatous polyposis: occurs in the colorectum in the majority of patients, and in the small intestine in a small percentage, and may eventually lead to cancer (especially in the duodenum). May arise from mutations or copy number abnormalities in the APC gene.

Hereditary nonpolyposis colorectal cancer: also known as Lynch syndrome, mostly from abnormalities in the genes MLH1, MSH2, MLH3, MSH6, TGBR2, PMS1, and PMS2.

Others: such as Boyds-Yeager syndrome, MYH gene-related polyposis, cystic fibrosis, etc. have a significantly increased probability of inducing intestinal cancer.

Other factors

The incidence of colorectal cancer is higher in molybdenum-deficient areas, and there are more colorectal cancer cases among asbestos workers.

The risk of rectal or sigmoid cancer in patients with cervical cancer treated with localized radiation therapy increases with the dose of radiation therapy.

Chronic inflammatory diseases of the small intestine can also induce cancer, such as wheatgum enteropathy which may increase the risk of small intestinal lymphoma and adenocarcinoma, Crohn’s disease which may increase the risk of small intestinal adenocarcinoma, and other immunoproliferative disorders, colon cancer, etc., which may be high-risk factors.

Pathogenesis

The development of colorectal cancer is a multifactorial, multistep and complex pathological process, and its specific pathogenesis has not been fully elucidated.

Research confirms that both intrinsic genetic factors and extrinsic environmental factors play important roles.

Symptoms

Early stage of colorectal cancer has no obvious symptoms or atypical symptoms, such as nausea, abdominal distension and loss of appetite, etc. When the tumor grows to a certain extent, it will have different clinical manifestations according to its different growth sites.

Tips] For more detailed symptoms of colorectal cancer, please refer to the entries of corresponding diseases.

Main Symptoms

Colorectal Cancer

Right hemi-colon cancer

Abdominal pain: 70% to 80% of patients with right half colon cancer have abdominal pain, which is mostly hidden.

Change of bowel habit: constipation or alternating between constipation and diarrhea, increased frequency of bowel movement.

Abdominal mass: abdominal mass is also a common symptom of right-sided colon cancer. Very few patients may have abdominal mass accompanied with intestinal obstruction.

Anemia: manifested as pale face, accompanied by dizziness, fatigue, shortness of breath and other symptoms. It is caused by necrosis, detachment of cancerous foci and chronic blood loss, and hemoglobin is lower than 100 g/L in 50%-60% of patients.

Many patients with right half colon cancer have no obvious symptoms in early stage, and they have anemia, fatigue, emaciation for unknown reasons, and even long-term ineffective treatment with anemia before colonoscopy is performed to confirm the diagnosis.

Left colon cancer

Blood in stool or mucous blood in stool: more than 70% of patients may have blood in stool or mucous blood in stool.

Abdominal pain: about 60% of the patients have abdominal pain, which can be hidden pain or abdominal colic when obstruction occurs.

Abdominal mass: about 40% of patients can touch the left side of the abdominal mass.

Bowel obstruction: the probability of abdominal mass accompanied by bowel obstruction is significantly higher than that of right colon cancer.

Rectal cancer

Blood in stool: blood and mucus on the surface of stool, or even pus and blood in stool.

Change of defecation habit: frequent bowel movement, with feeling of falling down from anus, accompanied by urgency and heaviness, and feeling of incomplete defecation.

Change of stool character: with the growth of tumor obstructing the intestinal canal, the stool gradually becomes deformed and thin. In serious cases, it may lead to intestinal obstruction.

Small Intestine Cancer

Abdominal pain: it is a common symptom in patients with middle or late stage.

Abdominal mass: often palpable, irregular in shape, lobulated, hard and often with pressure pain.

Digestive tract bleeding: there may be symptoms of acute blood loss such as vomiting blood, black stools, fresh blood stools and weakness, fatigue, dizziness, blurred eyes, pallor, cold limbs, cold sweat, palpitation, uneasiness, thin pulse and even fainting.

Intestinal obstruction: mostly incomplete intestinal obstruction, which may manifest as abdominal pain, abdominal distension, vomiting, and cessation of defecation.

Intestinal perforation: abdominal pain often occurs suddenly, usually persistent severe pain, often intolerable to the patient, and worsened during deep breathing and coughing.

Other symptoms

The tumor may cause consumption, lack of appetite, etc., leading to weakness with weight loss.

Consultation

Department of Medicine

Gastroenterology

Please consult the Department of Gastroenterology if you experience symptoms such as abdominal pain, abdominal mass, cessation of anal defecation, blood in the stool, change in bowel habits and change in stool texture.

General Surgery

If you are diagnosed with intestinal cancer and need surgical treatment, you can choose to visit the Department of General Surgery or the Department of Gastrointestinal Surgery.

Medical Oncology

If you are diagnosed with bowel cancer and need medication, you can go to the Department of Medical Oncology to receive systematic and standardized treatment.

Preparation for medical treatment

Consultation: Registration, Preparation of Documents, Frequently Asked Questions

Consultation Tips

When you visit the doctor, you may need to undergo relevant examinations. Please choose clothes that are easy to put on and take off, so that the doctor can conduct a physical examination.

Record the symptoms, duration and other relevant information for the doctor’s reference.

Preparation Checklist

Symptom Checklist

Its need to pay attention to the time of occurrence of symptoms, special manifestations, etc.

Have you had any unexplained bloody stools, black stools and other symptoms recently?

Any unexplained abdominal pain, abdominal masses, bloating, vomiting and other discomforts?

Are there any changes in bowel habits, such as constipation alternating with diarrhea?

Is there any gradual deformation and thinning of stools?

Is there any unexplained weight loss?

List of medical history

Are there any patients with malignant tumors such as intestinal cancer in the family?

Are there any underlying diseases such as familial adenomatous polyposis, intestinal polyps, enteritis, Crohn’s disease, etc.?

Are there any drug or food allergies?

Checklist

Test results of the last six months, which can be brought to the doctor’s office

Laboratory tests: blood routine, stool routine + occult blood, blood biochemistry tests.

Imaging examination: abdominal ultrasound, abdominal X-ray, CT, MRI, PET-CT, etc.

Specialized examination: tumor markers, gastroenteroscopy, histopathological examination

Diagnosis

Diagnosis is based on

Medical history

The patient may have the following medical history:

A history of familial adenomatous polyposis, intestinal polyps, enterocolitis, and Crohn’s disease.

A family history of bowel cancer.

Chronic smoking, excessive alcohol intake, obesity, and low activity.

Chronic high animal protein, high fat and low fiber diet.

Clinical manifestations

Symptoms

Patients may have symptoms such as abdominal pain, abdominal mass, intestinal obstruction, blood in stool, change of bowel habit and change of stool character.

Signs

Early patients may have no obvious signs.

In some patients, enlarged lymph nodes in the groin or supraclavicular region may be palpable.

Patients with long-term blood in stool may have anemia such as pale face, weakness, fatigue, dizziness and tinnitus.

The doctor inserts the index finger into the patient’s anus for rectal fingerprinting to check the rectum for lumps.

Palpation of the abdomen in patients with intestinal perforation may show pressure pain, rebound pain and muscle tension.

Auscultation of the bowel sounds are weakened, absent or hyperactive, etc., which helps to help determine the condition.

Laboratory Tests

Routine tests

Blood routine: to find out whether there is anemia, etc.

Urine routine: observe whether there is hematuria, combine with urinary imaging to know whether the tumor invades the urinary system.

Stool routine + occult blood: to determine whether there are red blood cells, white blood cells and other abnormalities. It is valuable for the diagnosis of small amount of gastrointestinal bleeding.

Biochemical examination: help to determine whether the liver and kidney functions are abnormal, whether there are electrolyte disorders, dyslipidemia, etc., and guide the next step of treatment.

Tumor marker examination

CEA, CA199, CA724 and other serum tumor markers are helpful for the auxiliary diagnosis, efficacy judgment and follow-up monitoring.

Imaging examination

Ultrasonography

Abdominal ultrasound is now a common non-invasive examination for the diagnosis of digestive system diseases.

Intestinal endoscopic ultrasound can clearly show the level and depth of intestinal tube invaded by the tumor, which helps to determine the T-stage of the tumor.

X-ray examination

Abdominal plain film is helpful in diagnosing intestinal perforation and intestinal obstruction.

CT examination

It helps to determine the location, size and scope of the tumor, especially when accompanied by intestinal obstruction.

It can help to carry out staging diagnosis, evaluate local invasion, lymph node metastasis and distant metastasis of the tumor, and provide a more reliable basis for the design of surgical plan.

CT examination is often used as the main examination tool for the follow-up of patients with bowel cancer to evaluate the therapeutic efficacy by comparing with the previous imaging results.

MRI examination

Pelvic MRI is a routine examination program for rectal cancer. For patients with locally progressive rectal cancer, it helps to evaluate the effect of neoadjuvant therapy.

When liver metastasis is suspected by clinical or ultrasound/CT examination, liver enhancement MRI is usually required.

Positron emission computed tomography (PET-CT)

Not routinely used, but can be used as an effective adjunctive examination for patients with complex disease whose distant metastases cannot be comprehensively evaluated by existing examinations.

Endoscopy

Through anoscopy, sigmoidoscopy, fiberoptic enteroscopy, etc. can directly observe the lesions in the lumen of the digestive tract and biopsy under direct vision to clarify the etiology of the diagnosis.

Pathological examination

Pathological examination is the most reliable diagnostic method for intestinal cancer, which is the basis for clear diagnosis and formulation of treatment plan.

Staging

Regarding the staging of bowel cancer, it needs to be determined according to the specific location of the disease.

For the staging of colorectal cancer and small bowel cancer, please refer to the section on diagnosis of colorectal cancer and small bowel cancer.

Differential diagnosis

Bowel cancer should be differentiated from benign bowel diseases, metastatic tumors, peptic ulcers, tuberculous colitis, and hemorrhoids:

Benign diseases of the small intestine

Similarities: both may present with abdominal pain, abdominal mass, abdominal distension and other symptoms.

Differences: benign small intestinal tumors are localized elevated lesions with smooth surface and normal villous structure, which can be easily distinguished from small intestinal cancer. However, if the tumor is large and combined with erosion and necrosis, it needs dissection or repeated histological examination to confirm the diagnosis.

Metastatic tumor of small intestine

Similarity: both of them can present abdominal pain, abdominal mass, gastrointestinal bleeding, intestinal obstruction and other symptoms.

Differences:

In addition to the above symptoms, it is often accompanied by primary tumor-related manifestations. For example, if cervical cancer metastasizes to small intestine, there may be symptoms such as irregular vaginal bleeding and vaginal discharge.

It needs to be clear that it is primary malignant tumor and not caused by direct invasion of primary foci, which is confirmed by caesarean section or specific examination and histology.

Peptic ulcer

Similarities: right hemicolon cancer and peptic ulcer both have epigastric discomfort or pain, fever, positive fecal occult blood test, and right upper abdominal mass.

Differences: Peptic ulcer can often be diagnosed by combining history, clinical manifestations, endoscopy and special examination findings.

Tuberculous colitis

Similarities: Cancer of the left half of the colon or rectum and tuberculous colitis are often associated with mucous blood stools or pus-blood stools, frequent bowel movements or diarrhea.

Differences: Tuberculous colitis may be accompanied by symptoms of tuberculosis toxicity such as hot flashes, night sweats, malaise, lack of appetite, and emaciation. Differential diagnosis can be helped by colonoscopy and physical examination.

Hemorrhoids

Similarity: Both rectal cancer and internal hemorrhoids have blood in stool.

Differences: Patients with rectal cancer often have anorectal irritation symptoms at the time of consultation. Anorectal fingerprinting or proctoscopy can usually differentiate them.

Treatment

Treatment objective: apply multiple treatment means in a planned and reasonable way to maximize the survival time of patients, improve the survival rate, control the tumor progression and improve the quality of life of patients.

Treatment principle: once the diagnosis of intestinal cancer is clear, treatment should be started as early as possible. At present, the treatment method is mainly based on surgery, combined with chemotherapy, radiotherapy, molecular target therapy and interventional therapy.

Tips: For more information about treatment, please refer to the related disease articles.

Surgery

Early diagnosis and early treatment is the key step to improve the overall efficacy of colorectal cancer, as early diagnosis and early treatment is the key step to improve the overall efficacy of colorectal cancer.

Colorectal Cancer

The most effective treatment for colorectal cancer is surgical resection, especially radical resection.

Surgical methods include right hemicolectomy, transverse colectomy, left hemicolectomy and sigmoid colectomy, abdominoperineal colectomy for rectal cancer (Miles’ surgery), and low anterior resection of the rectum (Dixon’s surgery), etc. The surgical methods and the scope of resection should be decided according to the location of the tumor, the extent of invasion and metastasis, and whether or not accompanied by intestinal obstruction, and also in combination with the systemic condition of the patient.

Small bowel cancer

For patients with clear diagnosis of small bowel cancer, early surgical treatment should be performed, including open surgery and laparoscopic surgery. The specific operation method depends on the location and stage of the tumor.

For patients with recurrence, surgery is the first treatment option.

Chemotherapy

Chemotherapy is a systemic treatment using cytotoxic drugs to destroy cancer cells, which can be broadly divided into postoperative adjuvant therapy, preoperative neoadjuvant chemotherapy and palliative chemotherapy.

Chemotherapy for Colorectal Cancer

Commonly used chemotherapy programs are as follows:

Simple chemotherapy

Modified FOLFOX6 regimen: oxaliplatin, calcium folinate, fluorouracil (5-FU).

CapeOX regimen: oxaliplatin, capecitabine.

Modified FOLFIRI regimen: irinotecan, calcium folinic acid, fluorouracil.

Chemotherapy regimens containing molecularly targeted therapies

Chemotherapy regimens containing irinotecan or oxaliplatin may be used in combination with bevacizumab or cetuzumab.

Other molecularly targeted therapies include furaquintinib and regorafenib.

For metastatic colorectal cancer with mismatch repair gene deletion, or highly unstable microsatellite type, immune checkpoint inhibitors (e.g., PD-1 monoclonal antibody) etc. have better efficacy.

Chemotherapy for small bowel cancer

Commonly used chemotherapy regimens are as follows:

Chemotherapy There is no standardized treatment protocol for small bowel cancer. The efficacy of postoperative chemotherapy is controversial.

The chemotherapy regimens used are mostly borrowed from those of colon cancer or gastric cancer, and most of them use fluorouracil as the basic drug, emphasizing individualized chemotherapy regimens.

Radiotherapy

Radiation therapy for tumor is referred to as radiotherapy, which is a local treatment means, and can be used to destroy and eradicate local primary tumors or metastatic foci, and can be used to treat tumors alone.

Colon Cancer

Radiotherapy is generally not used as a routine treatment. Patients with metastasis in supraclavicular lymph nodes or retroperitoneal lymph nodes have certain curative effect by applying local irradiation of radiotherapy.

Rectal cancer

Tumor shrinkage can be achieved by preoperative neoadjuvant radiotherapy, which can improve the rate of radical surgical resection; reduce the risk of lymph nodes and local recurrence.

Small bowel cancer

Except for small bowel sarcoma which has some sensitivity to radiotherapy, most small bowel cancers are insensitive to radiotherapy and radiotherapy is usually not chosen, but for small bowel carcinoid tumors with multiple metastases in the liver, radiotherapy has the effect of relieving symptoms.

Molecular Targeted Therapy

Molecular targeted therapy is a therapeutic method that targets the specific (or relatively specific) molecules possessed by tumor tissues or cells, and uses molecular targeted drugs to specifically block the biological function of the target, so as to achieve the therapeutic method of inhibiting the growth of tumor cells or even clearing the tumor.

At present, the commonly used molecular targeting drugs in colorectal cancer are cetuximab and bevacizumab. There are also furaquintinib, regorafenib and so on.

For small bowel cancer, targeted therapy is still in the research stage at this stage, and there is not much evidence at the moment.

Immunotherapy

Tumor immunotherapy is to make use of the body’s immune mechanism to enhance the patient’s immune function through active or passive methods to achieve the purpose of killing tumor cells, and immune checkpoint inhibitors are commonly used.

Navulizumab and pabolizumab, are commonly used in the treatment of patients with metastatic colorectal cancer with microsatellite instability and have better efficacy.

Interventional therapy

Arterial embolization chemotherapy has certain therapeutic value for small bowel cancer with rich blood supply, but it is seldom used due to poor selectivity and high side effects, and is mainly used for the treatment of liver metastasis of small bowel cancer.

Prognosis

Cure

At present, bowel cancer cannot be completely cured, but with active and standardized treatment, some patients can have the chance of clinical cure.

The likelihood of clinical cure is usually roughly assessed using statistical data such as 5-year survival rate.

The prognosis of different types of bowel cancer varies.

Colorectal Cancer

The 5-year survival rates of colorectal cancer by stages are 90%-95% for stage I, 80%-85% for stage II, 60%-70% for stage III and less than 20% for stage IV respectively. If stage IV patients can receive radical surgery for metastatic foci, the 5-year survival rate is about 40%.

Small bowel cancer

Small bowel cancer has the worst prognosis, and the 5-year survival rate of each clinical stage is 55% in stage I, 49% in stage IIA, 35% in stage IIB, 31% in stage IIIA, 18% in stage IIIB, and only 5% in stage IV.

Special Reminder

Statistical data such as 5-year survival rates are for clinical studies only and do not represent individual specific survival.

Survival should be analyzed in conjunction with the stage of disease onset, physical condition, and whether the patient has received standardized treatment in a timely manner and regular review.

Prognostic factors

Prognostic factors refer to a series of factors that may affect the survival time and quality of life of patients. Prognostic factors of bowel cancer are closely related to the location of the disease and cannot be generalized. In addition the common prognostic factor is the stage, the earlier the stage the better the prognosis.

For more detailed prognostic factors, please refer to the section on Prognosis of Colorectal and Small Bowel Cancer.

Daily

Daily management

Dietary management

Reasonable dietary arrangement, pay attention to eat more food rich in nutrients and easy to digest.

More vitamin-rich fresh fruits and vegetables can be consumed to replenish the vitamins needed by the body and promote recovery.

Eat more protein-rich foods, such as eggs, milk, lean meat and fish.

Cold, raw, stimulating, pickled, fried and deep-fried foods, such as fried chicken and chili peppers, should be avoided.

Life management

Avoid exertion, regular work and rest, and ensure sufficient sleep.

Proper exercise is needed in daily life to improve physical fitness and avoid low immunity.

Maintain a healthy body weight and take appropriate activities, such as slow walking, tai chi, qigong and breathing exercises.

Psychological support

Maintain a good mood and mindset to face the disease positively.

Learn to confide in friends and family members to avoid excessive pressure, which may cause mental illness, and seek help from a psychiatrist if necessary.

Patients should establish a correct understanding of the disease, accept treatment positively, and do work and housework to the best of their ability during and after treatment, so as to reintegrate into social roles.

Family members should provide adequate companionship to the patient, create a cozy family atmosphere, comfort the patient and help him/her to tide over the difficult times.

Disease monitoring

Patients should pay attention to the daily observation of physical manifestations. If symptoms such as abdominal pain, abdominal mass, intestinal obstruction, blood in the stool, change in bowel habit and change in the character of stool reappear or worsen again, they should seek medical advice promptly.

Follow-up examination

The following follow-up is for scientific reference only. For specific follow-up plan, please consult your doctor in detail and strictly follow the doctor’s instructions.

History taking and physical examination every 3 to 6 months for 2 years, and then every 6 months for a total of 5 years.

Chest/abdominal/pelvic CT every 6 to 12 months for 2 years and then every year for 5 years.

Tumor marker CEA/CA199 test, 1 every 3 to 6 months for 2 years, and then every 6 months thereafter for a total of 5 years.

Colonoscopy, once a year for 5 years

Note: If you have any discomfort, please seek medical attention at any time.

Prevention

The cause of bowel cancer is currently unknown, and depending on the possible causative factors, it may be helpful to reduce the incidence of the disease through the following measures

Improvement of lifestyle

Rationalize your diet and eat more fresh vegetables, fruits and other foods rich in carbohydrates and crude fibers.

Consuming appropriate amount of calcium, molybdenum and selenium can help prevent colorectal cancer.

Actively treat underlying intestinal diseases such as ulcerative colitis, polyposis, adenoma and Crohn’s disease.

Adopt a good lifestyle, do not smoke, do not abuse alcohol, eat a balanced diet, be physically active, control weight and prevent obesity.

Have regular medical checkups

People with underlying intestinal diseases, positive fecal occult blood and family history of bowel cancer should actively treat the underlying diseases and undergo regular colonoscopy.