Overview
There is no clear definition, mostly refers to colon cancer that has not yet infiltrated and metastasized usually no obvious symptoms, a small number of patients may have blood in the stool and other manifestations of genetic, environmental and lifestyle factors that lead to a good prognosis, most of the long term survival
Definition
At present, there is no clear and unified definition of early colon cancer (ECC) at home and abroad [1].
According to domestic guidelines, early colon cancer refers to cancer cells confined within the lamina propria of the mucosa, or infiltrating through the muscular layer of the colonic mucosa to the submucosal layer, but not involving the lamina propria [2-3].
According to foreign guidelines, there is no specific definition of early colon cancer, which mostly refers to cT1~T2 stage colon cancer.
In clinical studies, multiple criteria also exist for the diagnosis of early colon cancer, such as TisN0M0 colon cancer [4], stage I versus stage II colon cancer [5], and stage I to IIIC colon cancer [6].
This term describes early stage colon cancer using the criteria of the national guidelines, that is, cTisN0M0 stage and cT1N0M0 stage colon cancer [3,7].
Colonoscopy is the gold standard for early screening and diagnosis of early colon cancer, through which structural changes in the mucosa of the intestinal wall can be observed, and tissue can be directly microscopically clamped to confirm the diagnosis by pathology.
Typing
Histologic type
According to the World Health Organization (WHO) classification of digestive system tumors, early colon cancer can be divided into adenocarcinoma, adenosquamous carcinoma, squamous cell carcinoma, spindle cell carcinoma/sarcomatoid carcinoma, and undifferentiated carcinoma.
Adenocarcinoma
It is the most common histologic type.
Depending on the degree of differentiation of the tumor’s glandular structures, it can be further classified into highly differentiated, moderately differentiated, and poorly differentiated adenocarcinomas.
The degree of differentiation indicates the degree of difference from normal cells. Highly differentiated ones have a relatively small degree of difference, suggesting a relatively low degree of malignancy, while lowly differentiated ones are the opposite.
Mucinous adenocarcinoma
It is composed of mucus-secreting cancer cells, and there is a large amount of mucus in the cancer tissue.
The degree of malignancy is high.
Indolent cell carcinoma
The tumor consists of diffuse patches of impression cells. The nuclei of the imprinted cells are deeply stained, favoring one side of the cytoplasm, and the whole cell looks like a ring under the microscope.
It is highly malignant and has a poor prognosis.
Adenosquamous carcinoma
The tumor consists of adenocarcinoma cells and squamous carcinoma cells.
Its differentiation is mostly moderate to low.
It is less common.
Undifferentiated carcinoma
The cancer cells are diffuse in the form of sheets or clusters, do not form glandular tubular structures, the cells are arranged irregularly, and the cancer cells are smaller and more uniform in shape.
Poor prognosis.
Incidence
Colon cancer is the “number one tumor” of digestive tract in China.
In 2020, the number of new cases of colon cancer in China will be 560,000 and the number of deaths will be 290,000, which is the second highest incidence of cancer in China.
It is the second most prevalent cancer and the fifth most deadly cancer in China, posing a serious threat to national health.
The incidence rate is gradually increasing, and it has been reported that between 2011 and 2020, the incidence rate of colorectal cancer in China increased by 126%, with an average annual growth rate of 9.5%.
At present, there is no authoritative statistical data on the early stage of colorectal cancer in China, but most of the patients are diagnosed in the middle or late stage, and the proportion of patients with early colorectal cancer is only about 20% to 30%.
Causes
Causes
Colon cancer is the result of a combination of factors, and early colon cancer reflects the early stage of colon cancer.
Risk factors
A large amount of research evidence indicates that the development of colon cancer is the result of the joint action of genetic, environmental and lifestyle factors, which are called risk factors of colon cancer.
The risk factors that have been established by current research are as follows [2]:
Family history of colorectal cancer
Family history of colorectal cancer is associated with an increased risk of developing colorectal cancer.
It has been noted that the risk of developing colorectal cancer in first-degree relatives is 1.76 times higher than that of the general population.
Dietary factors
About 50% of colorectal cancers are associated with dietary factors, such as high-fat and high-protein diets, high-temperature cooking of meat and fish foods, and diets lacking fresh vegetables and fiber [10-12].
Red meat and processed meat intake is associated with an increased risk of colorectal cancer.
Lifestyle habits
Smoking and heavy alcohol consumption are associated with increased risk of colorectal cancer.
Inflammatory bowel disease
Chronic inflammation caused by ulcerative colitis, colonic Crohn’s disease, and colonic schistosomiasis causes repeated destruction and repair of the intestinal mucosa, leading to a much higher risk of developing cancer [13-16].
Obesity.
For every 5 kg/m2 increase in body mass index (BMI), the risk of colon cancer increases by about 5%, and for every 10 cm increase in waist circumference, the risk of colon cancer increases by 2%.
Others
The China Chronic Disease Prospective Study (CKB), which included 500,000 people for follow-up, found that people with diabetes detected by on-site physical examination had a 44% increased risk of colorectal cancer compared to the general population.
Patients who had received radiotherapy for previous gynecological tumors such as breast, ovarian, and cervical cancer had a higher risk of colon cancer than the normal population.
Protective factors
However, studies have also found that there are some factors that may reduce the risk of colon cancer, known as protective factors.
Aspirin
Existing studies suggest that aspirin may reduce the risk of colon cancer. However, because of the possibility of side effects such as gastrointestinal bleeding, it is not recommended that the public blindly use aspirin on their own to prevent colon cancer.
Dietary Habits
Existing research evidence suggests that intake of dietary fiber, whole grains, and dairy products may reduce the risk of colorectal cancer [17-20].
Reasonable physical activity
Several studies have found that reasonable intensity and duration of physical activity can significantly reduce the risk of colon cancer.
Pathogenesis
The development of colon cancer, like the development of other tumors, is the result of multifactorial, multistep, internal and external factors interacting with the colon through multiple stages of cancer induction, cancer promotion and evolution.
Tumors are formed gradually by the combination of internal and external factors, and the accumulation of genetic changes in the cells, thus having the developmental sequence of “normal epithelium-adenoma-cancer”, which is the classical molecular event pattern of colon cancer.
Carcinogenesis is a complex process involving multiple genes and multiple steps, many of which need to be elucidated and improved by further research.
Symptoms
Early stage colon cancer usually has no obvious symptoms[3], and the following symptoms may appear when the disease has progressed to a certain degree, but these symptoms may appear in many kinds of intestinal diseases, so we cannot judge whether it is early stage colon cancer based on the symptoms alone.
Change of bowel habit
Patients may show constipation, or alternating between constipation and diarrhea, increased frequency of bowel movements, etc.
Change of stool character
Some patients may have bloody stools, mucus stools, etc.
Abdominal pain and bloating
Often, the pain is persistent and not precisely localized, or only abdominal discomfort or bloating.
Consultation
Department of Medicine
Gastroenterology
It is recommended to consult a doctor if you have any of the following symptoms.
Persistent abdominal discomfort, vague pain, or flatulence in the recent past.
Change in bowel habits, constipation or diarrhea, or alternating between the two.
Blood in the stool.
General Surgery
If you have any of the above symptoms, or if you have been diagnosed with early stage colon cancer that requires surgical treatment, you may also visit a general surgery or gastrointestinal surgery center.
Preparation for medical treatment
How to get to the doctor: registering, preparation of documents, and frequently asked questions
Tips for medical treatment
Before going to the doctor, try to keep a record of the symptoms you have experienced, their duration, etc. for the doctor’s reference.
Preparation List
Symptom list
Pay particular attention to the time of onset of symptoms, special manifestations, etc.
Is there any abdominal pain and for how long?
Has there been blood in the stool recently?
Are there any changes in bowel habits, such as constipation alternating with diarrhea?
What does the stool look like and is there mucus?
List of medical history
Is there any family history of malignant tumors such as bowel cancer in the family?
Any history of colon adenoma, etc.?
Is there any smoking or alcohol consumption?
What is your diet like, do you like red meat or processed meat?
Any ulcerative colitis, Crohn’s disease?
Checklist
Test results of the last six months, which can be brought to the doctor’s office
Specialized tests: colonoscopy and biopsy results (any within 5 years), tumor markers, fecal occult blood test.
Laboratory tests: blood routine, urine routine, stool routine, biochemical tests.
Imaging examination: CT examination, magnetic resonance (MRI), PET-CT.
Diagnosis
Diagnosis is based on
Medical History
When the doctor makes a clinical diagnosis, some patients may have the following relevant medical history.
A history of ulcerative colitis and Crohn’s disease.
A family history of colorectal cancer.
Long-term smoking, excessive alcohol intake, obesity, and low activity.
Clinical manifestations
There may be no obvious clinical manifestations or the following symptoms may be present.
Presence of blood or mucous blood stools, or persistent positive fecal occult blood test.
Recent changes in bowel habits.
Recent onset of abdominal distension and vague abdominal discomfort.
Laboratory Tests
Fecal Occult Blood Test
Fecal occult blood test may be positive when intestinal bleeding is small and not visible to the naked eye.
Multi-targeted fecal FIT-DNA test
Multi-target fecal FIT-DNA test is to determine whether there is a possibility of colon cancer by measuring the abnormal changes of some specific molecules in the intestinal exfoliated cells carried by feces, which has the advantages of non-invasive, convenient and accurate [21-23].
Tumor markers
Peripheral blood carcinoembryonic antigen (CEA) and glycoconjugate antigen 19-9 (CA19-9) are generally required to be tested in patients with early-stage colon cancer at the time of diagnosis, prior to treatment, when evaluating the efficacy of treatment, and during follow-up.
CEA and CA19-9 are generally not used for screening, which means that their values do not indicate a high or low risk of having colon cancer and are more useful for disease monitoring.
Patients who continue to have elevated CEA and CA19-9 after surgery often have residual disease.
If CEA and CA19-9 return to normal after surgery, but increase again in the future, it often indicates tumor recurrence.
Colonoscopy
Colonoscopy (including polyp biopsy and pathologic examination) is the gold standard for the diagnosis of early colon cancer and precancerous lesions, and is also an important means of treating colon lesions.
Colonoscopy and lesion removal can reduce the incidence of colon cancer by 76% to 90% and mortality by 53% [24].
Imaging
Imaging tests other than CT are generally used less frequently for screening of colon cancer, but are performed mainly after the suspicion or diagnosis of the presence of colon cancer.
CT examination
It helps to know the size of tumor, invasion of adjacent organs, involvement of lymph nodes and the presence of distant metastases, etc. It is of great significance to preoperative staging.
Gas-barium double contrast examination
Mainly used to exclude multiple cancers and polyposis.
Intraluminal ultrasonography
It can detect the depth of tumor infiltration into the intestinal wall and the involvement of adjacent organs, which is of great value in guiding the preoperative assessment of clinical staging of tumor and selection of surgical methods.
PET/CT examination
It is generally not a routine examination method for early colon cancer.
For colon cancer patients with long course and fixed tumors, in order to exclude distant metastasis and evaluate whether there is recurrence after surgery, PET/CT examination can be considered when available.
Staging
Early stage colon cancer in this article mainly includes patients with clinical staging of cTisN0M0 and cT1N0M0.
Meaning of clinical staging
Abbreviated as cTNM (clinical TNM), it is the pre-treatment staging, i.e., based on the information before the first clinical treatment.
This information can come from physical examination, imaging, endoscopy, biopsy, surgical exploration and other relevant tests, and is based on the combined judgment of a medical professional.
The cTNM is particularly important in selecting and evaluating treatments and the timing of treatment.
cTisN0M0 stage
It mainly refers to colon cancer with a relatively superficial location and no metastasis.
Tis refers to carcinoma in situ, intramucosal carcinoma (involvement of the lamina propria without extension through the muscular layer of the mucosa).
N0 indicates no lymph node metastasis.
M0 indicates no metastasis to distant organs.
cT1N0M0 stage
T1 is defined as tumor invasion of the submucosal layer of the colon wall (through the mucosal muscularis propria, but not into the lamina propria).
N0 indicates the absence of lymph node metastasis.
M0 indicates the absence of metastasis to distant organs.
Differential diagnosis
The differential diagnosis of early colon cancer is mainly colon polyps, ulcerative colitis, Crohn’s disease, intestinal tuberculosis, chronic bacillary dysentery, schistosomiasis, and amoebic enteropathy.
The most reliable differential is through colonoscopy to take a biopsy.
Colonic polyps
Similarities: Polypoid lesions such as tubular adenomas of the colon and inflammatory polyps of the colon are called polyps or polypoid lesions until the nature of the pathology is clarified. Larger polyps can also cause abdominal cramps and constipation.
Differences: Colon polyps are usually clearly diagnosed by colonoscopy and gas-barium double contrast.
Ulcerative colitis
Similarities: Both have digestive symptoms such as abdominal pain and diarrhea.
Differences
Age of onset: ulcerative colitis is most common in patients aged 20 to 40; colon cancer has a higher incidence rate at the age of 40 to 65.
Characteristics of diarrhea: in ulcerative colitis, diarrhea is heavy for 10 times a day; in light cases, only loose stools are found for 3 to 4 times a day; in colon cancer, it is constipation or constipation and diarrhea alternately.
Crohn’s disease
Similarities: both present with abdominal pain, diarrhea and weight loss.
Differences
Crohn’s disease is often accompanied by fever.
There may be systemic damage to several systems, and thus a series of extra-intestinal manifestations, including: pestle fingers (toes), arthritis, erythema nodosum.
Chronic bacillary dysentery
Similarities: both have abdominal pain, abdominal distension, diarrhea, or diarrhea alternating with constipation and other clinical manifestations.
Differences: chronic bacillary dysentery often has a history of acute bacillary dysentery; dysentery bacilli can be isolated in fecal examination; colonoscopy with mucopurulent secretion culture has a higher positive rate; antimicrobial therapy is effective.
Amebic enteropathy
Similarities: both have changes in bowel habits or occasional clinical manifestations such as blood in the stool.
Differences: fecal or colonoscopic examination of the ulcerated exudate can be found in the histolytic amoebic trophozoites or capsules. Serum anti-amoebic trophozoite antibodies are positive. Anti-amoebic therapy is effective.
Treatment
Aim of treatment: radical resection of the tumor and clinical cure as far as possible.
Treatment principle: give priority to resection through endoscopy, take local resection or intestinal segmental resection if necessary, generally do not need adjuvant chemotherapy.
Endoscopic treatment
Early stage colon cancer is limited to the mucosa and above the submucosa, most of which can be minimally invasively treated by endoscopy.
Indications
If resection or local excision is to be performed through endoscopy, the following requirements must be met [3].
Maximum diameter of the tumor <3 cm.
Tumor invades <30% of the intestinal perimeter.
Cutting edge >3 mm from the tumor.
Tumor is active and not fixed.
Only for T1 stage tumors.
Highly-moderately differentiated.
No signs of lymph node metastasis on imaging prior to treatment.
Treatment options
Include endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD).
For early stage colon cancer, endoscopic submucosal dissection has a higher rate of whole resection and complete resection.
The whole resection rate of endoscopic mucosal dissection is about 85%, and the complete resection rate is 68.6% to 86% [25-26].
Endoscopic submucosal dissection has a block resection rate of 88% to 98.3% and a complete resection rate of 89% to 92% [27-28].
Intestinal segmental resection
If the preoperative endoscopic ultrasonography is stage T1 or if the local resection is pathologically confirmed to be stage T1 after resection, further surgical resection is not recommended if the tumor is resected intact, has negative margins (including the base), and has histologic features with a good prognosis (e.g., well-differentiated, no chorioallantoic infiltration).
If there are histologic features with a poor prognosis, or if the resection is incomplete and specimen fragmentation margins cannot be evaluated, additional bowel segmental resection with regional lymph node dissection is recommended.
Prognosis
Cure
After endoscopic treatment of early stage colon cancer, patients generally survive for a long time and may have a normal life expectancy if regular follow-up is strictly adhered to.
Survival rate
The overall survival time of tumor patients can be roughly predicted by the 5-year survival rate, which refers to the proportion of patients who survive for more than 5 years after various comprehensive treatments.
The 5-year survival rate of early colorectal cancer is about 90% to 95%.
Special Reminder
Statistical data such as the 5-year survival rate is only used for clinical studies and does not represent the specific survival period of an individual.
Patients’ survival should be analyzed in combination with their stage of disease, physical condition, whether they have received standardized treatment in time and regular review, etc. It is recommended to consult the physician.
Prognostic factors
Prognostic factors refer to a series of factors that may affect the survival time and quality of life of patients.
The prognosis of early colon cancer is mainly related to early diagnosis and standardized treatment.
Daily
Daily management
Mindset and Emotion Adjustment
Good emotion and mindset cannot be replaced by drugs.
After diagnosis, patients may develop a sense of fear and may be afraid of pain, abandonment and death. Family members should pay attention to listen to the patient’s heart, improve the patient’s mental ability and relieve anxiety symptoms.
Encourage the patient’s family to give support so that the patient can face the surgery and other treatments positively with a good mindset.
During and after treatment, family members are advised to encourage the patient to do work and household chores that are within his/her ability to reintegrate into social roles.
Adjustment of lifestyle
Maintain a good and optimistic state of mind, moderate activity, and avoid exertion and exposure to cold.
Defecate regularly every day and gradually develop a regular bowel habit.
Do not participate in heavy labor for 1 to 3 months after surgery.
Dietary management
Foods to be eaten less
Regulate the dietary structure and eat less food that is easy to produce irritating odor or flatulence, such as onions, garlic, beans, yams, etc. [29].
Suggested foods to eat more of
High-calorie, high-protein, vitamin-rich foods with less residue, such as eggs and fish. Eating more fruits and vegetables helps to reduce the recurrence rate.
Review and follow up
Regular review is needed after colon cancer treatment.
Medical history, physical examination and CEA, CA19-9 monitoring
Year 1 to 2: every 3 months.
Years 3 to 5: 1 time every 6 months.
After 5 years: 1 time per year.
Thoracoabdominal/pelvic CT or MRI
Year 1 to 2: every 3 months.
3rd to 5th year: every 6 months.
After 5 years: 1 time per year.
Enteroscopy
Enteroscopy within 1 year after surgery; if abnormal, repeat within 1 year.
1 year after surgery, every 1 to 2 years. Any colorectal adenoma that appears on follow-up examination is recommended to be resected.
If preoperative colonoscopy is not completed for the whole colon, colonoscopy is recommended 3 to 6 months after surgery.
PET/CT
Not routinely recommended, PET/CT may be considered in patients with existing or suspected recurrence and distant metastasis to rule out recurrent metastasis.
Prevention
Improvement of lifestyle
Reasonable dietary arrangement, eat more fresh vegetables, fruits and other foods rich in carbohydrates and crude fiber.
Consuming appropriate amount of calcium, molybdenum and selenium can help prevent colorectal cancer.
Actively treat ulcerative colitis, polyposis, adenoma and Crohn’s disease.
Adopt a good lifestyle by not smoking, not abusing alcohol, eating a balanced diet, being physically active, controlling weight and preventing obesity.
Colorectal Cancer Screening
Screening Targets
The domestic recommended colorectal cancer screening target is the general population aged 40~74 years old, for high-risk groups, they should consult with professional physicians in detail and strictly follow the medical advice for colorectal cancer screening [2,9].
Screening program
Direct colonoscopy is recommended once every 5 to 10 years.
If the screened subject refuses to undergo direct colonoscopy, a specific colon cancer risk questionnaire is used for risk assessment, and a fecal occult blood test (FIT) is performed using an immunoassay method, and a colonoscopy is performed for those who are positive on the initial screening (high-risk group or FIT-positive).
If the screening subjects have poor compliance with colonoscopy, further multi-targeted fecal FIT-DNA testing can be performed, and those who are positive can then undergo colonoscopy, which can further qualify the high-risk group and improve the colonoscopic tumor detection rate.