Pathology of colorectal cancer

2021-01-27 12:00 AM

Epidemiological studies and in laboratory animals show that dietary fibre has a protective effect against the development of colon cancer.

Outline

Colorectal cancer is the leading cause of death in North America, Europe, after prostate cancer, breast cancer and lung cancer. In 1996, there were about 134,000 new cases in the United States and 55,000 deaths ranked second after lung cancer. By 2004, there were 146,940 new cases and 56, 730 deaths. There was a marked increase in colorectal cancer rates in low-prevalence countries before the 1950s. With the rapid progress in molecular biology, there was an insight into the pathogenesis of cancer. Colorectal, thereby posing a primary prevention problem because the disease occurs after a long time with interactions of genetic modification and environmental factors, so it is possible to detect the disease in the precancerous stage. and cancer at an early stage for treatment increases the life expectancy of the patient.

Epidemiology

Disease rates are high in developed countries such as North America, Australia, New Zealand, and countries in Europe, and low in countries in Asia, South America, Sahara, Africa. Geographical differences also showed that there was a difference in the location of colorectal cancer. For example, colon cancer in blacks was similar to that of whites but rectal cancer was taller. black and male than female. Immigrants from a place with a low rate of colon cancer to a place with a high rate also showed a faster increase in the incidence than in the old place. Countries with rapid growth rates are Italy, Portugal, moderate increases in Great Britain and Denmark, and stable rates in France and Switzerland. In terms of location, the incidence of cancer in the right and sigma tends to increase but the rate of cancer in the rectum is decreased, reflecting the different sensitivity of tumour morphology in the segment. Near and far of the colon.

Environmental factors play an important role in the development of the disease. In the same region, different lifestyles have different incidence, with foods linked to diseases such as foods rich in fat, protein, sugar, low in vegetables and fiber, and less trace elements.

This disease is more common in people over 50 years old.

Mechanism of pathogenesis

Most colorectal cancers usually arise from glandular polyps that adhere to the mucosal surface, including non-hyperplastic young polyps, hyperplastic polyps or adenocarcinoma. Only adenocarcinoma is clearly malignant and there is a small incidence of cancer. Polyp in the colon occurs over 30% in the middle age and the elderly, but only 1% is malignant. Most polyps have no symptoms and blood is hidden in the stool only in 55 cases.

Clinically, adenoma polyps become cancerous depending on their size, histological characteristics, and size. Cancer often arises from flat gland polyps, especially polyps with a diameter of> 2.5 cm. So, when detecting polyps, as soon as there is no evidence of malignancy, endoscopy should be periodically monitored every 5 years because these patients up to 30-50% may develop other adenoma polyps and There is an even higher risk for colon cancer.

 Risk factor

Diet

The disease occurs in developed countries, where there is a high socio-economic life, and urban residents. and is associated with a high-energy, fatty and fatty diet as well as in people with hypercholesterolemia and coronary artery disease.

Animal fat:

Fatty diet increases the synthesis of cholesterol and bile acids in the liver, increasing the amount of sterols in the colon. The bacteria in the gut convert these products into secondary bile acids and other substances that have toxic effects in the stool. These latter metabolites may damage the colon mucosa and increase arachidonic-mediated colon epithelial activity that increases carcinogenic prostaglandins.

Eating more red meat will increase the rate of anaerobic bacteria in the lumen that convert bile acids into carcinogens, especially colon cancer and sigmoid colon. Perhaps due to the difference in the proportion of saturated and unsaturated fat in the meat composition. Using fish oil high in Omega 3, a type of polyunsaturated fat, and olive oil, a monounsaturated type, is better than using animal fat. This risk factor is also seen in people with hypercholesterolemia and beta-lipo-protein in the blood.

Fiber:

Epidemiological studies and in laboratory animals show that dietary fiber has a protective effect against the development of colon cancer.

Its role is not well known. Bacteria in the colon also ferment fibers to form short-chain fatty acids, lower the pH of the colon, alter fecal properties and potentially inhibit carcinogens.

Carcinogenic factors, vitamins and trace elements:

Fecapentaenes: A metabolite of unsaturated fatty acids under the influence of colon bacteria also plays an important role in colon cancer.

Grilled meat and fish: Products created are amino acids with a ring structure that are also factors that cause cancer.

Beer and alcohol too, have a high risk of causing cancer when consumed in excess. It is also found that in people working in car repair factories, the rate of colon cancer is 2-3 times higher than normal people, it is not clear why.

Vitamins A, C: Work as antioxidants, work to prevent colon cancer. Fresh green vegetables and flower type vegetables, vitamin E, folic acid, calcium, and trace elements such as selenium also work to prevent colon cancer. However, the exact mechanism is not entirely known.

Insulin resistance

Physical activity is in reverse related. Obese, insulin-resistant individuals with hyperinsulinemia increase levels of type 1 insulin-like growth factor (IGF-

This factor will stimulate the proliferation of intestinal mucosa.

Genetic factors and syndromes

About 25% of patients with colorectal cancer have a family history of the disease, hints at the genetic predisposition. There are two main groups: familial polyps and cancer not caused by polyps that are inherited.

Colon polyps have a family nature: There are thousands of glandular polyps throughout the length of the colon. It is caused by a deficiency of one branch of chromosome 5, which is common after puberty around 25 years old and is likely to develop into cancer before the age of 40. Colon removal should be done when detecting this polyp, while with NSAIDs also reducing the number and size of polyps, but only temporary. The descendants of these patients require follow-up endoscopy even before puberty as there is an approximately 50% risk of developing precancerous disorders. Therefore, it is necessary to follow up with colonoscopy and sigmoidoscopy without the need to complete colonoscopy or baryte staining until age 35.

Colon cancer is not inherited: encountered at least 2 generations, is adenocarcinoma, occurred before the age of 50, encountered in colon up, can coordinate with ovarian cancer, endometrial cancer. The prognosis is better than polyps.

Enteritis

Colon cancer is increased in patients with chronic inflammatory bowel disease. Cancer is more likely to develop in ulcerative colitis than Crohn's disease and this risk increases from 8 to 30% in people with chronic inflammatory bowel disease lasting more than 25 years, especially in young adults with complete inflammation of the colon. Finding this complication is not by relapses of the disease, by endoscopy, by brushing but by dysplasia of the colon glands.

Other risk factors

Streptococcus bovis infection: Bacteria from the stool cause endocarditis or septicaemia that can cause latent colon cancer and high navigational cancer with unknown causes. Gastrointestinal endoscopy and x-rays are the screening tests.

Sigma: Cancer develops 25-30 years after surgery, where the sigmoid lining is always in contact with urine and faeces.

Tobacco: Especially in people who smoke continuously for more than 35 years. The cause is not clear.

Pathology

Colorectal cancer is predominantly adenocarcinoma, less common are colon lymphoma and carcinoid tumours. Cancer can be a single lesion site or in combination with polyps or it can have multiple lesions on the colon.

General

Just like stomach cancer, there are 3 possible types of colon cancer.

Cancer in the form of papules or polyps. Lesions may be broad, protruding and often villous papillae.

Ulcerative cancer: Commonly, with ulcerative images on the pulp.

Infiltrative cancers: Hard and thickened colon wall without ulcers on the mucosa. This type is less common but has a bad prognosis.

Micro

Most colon cancers are of the type of adenocarcinoma, with high, medium, or low differentiation. Approximately 20% of the epithelium secretes a lot of mucus, the epidermal type of epithelium with layered cells (this type is rare).

The prognosis depends on differentiation and distant spread or metastasis.

clinical

Colorectal cancer usually presents silently with its course over the years with no symptoms or only slight changes in bowel habits. Symptoms usually vary depending on the location of the tumour.

Because the stool is relatively loose when passing through the ileocecal valve to enter the right colon, with colon cancer up, there is little symptom of bowel obstruction or change in bowel habits. The right colon lesion usually takes the form of an ulcer that causes chronic dull blood loss without obvious stool changes. Patients often have symptoms of fatigue, palpitations, chronic anaemia, hypochromia due to iron deficiency, can touch the tumour in the right pelvic fossa or lower right rib. Because cancer is bleeding in waves, the blood test in the stool is sometimes negative.

Cancer in the transverse and descending colon: Denser stools, when the cancer grows to large enough, it causes a relative narrowing of the lumen of the colon or complete narrowing, sometimes causing perforation. Clinical manifestations of abdominal pain, type of semi-occlusion and intestinal obstruction

Colon and rectal cancer: Often manifestations of dysentery syndrome with haemorrhagic stools, flattened stools, and anaemia that is sometimes mistaken for haemorrhoids with bleeding. Rectal examination found tumours that were hard, painful, and bleed easily when touched.

Because the disease usually progresses silently, sometimes the disease is only detected when there are complications of intestinal obstruction or detecting the metastatic site of the cancer where the liver is the first metastasis site.

Subclinical

Sigmoidoscopy

This is a simple and fast procedure that helps detect 2/3 to 3/4 of rectal and sigmoid cancers in the presence of dysentery syndrome. It also helps to biopsy or remove the tumour when possible or treat haemostasis on the spot.

Complete colonoscopy

It is a very good diagnostic tool to help detect lesion location as well as biopsy for histological diagnosis.

Endoscopic ultrasound, CT scanner

It is a good means to diagnose localized lesions under the mucosa as well as to detect metastasis in nearby organs, helping to diagnose the stage of TNM.

Colon staining film with baryte

Detecting tumours> 2 cm in diameter, with ulcerative images, irregularly shaped narrowing of the lumen of the colon like apples. In cases where the tumour is less than 1cm, it is necessary to use double-ray radiography.

CBC

Red blood cells, Hb decrease when there is anaemia.

Serum iron

Reduces iron deficiency anaemia.

Symptoms

Bowel obstruction

Is a sign of complications as well as common complications of colorectal cancer, can be partially or completely blocked? Obstruction caused by a tumour or by compression of the lymph node.

Perforation

Perforation can occur directly in the tumour or on a special tumour in the cecum.

Pinch to neighbouring organs

Metastatic tumours and lymph nodes can cause compression of the stomach, compression of the bladder, compression of the visceral venous system causing ascites, compression of the nerves in the lower extremities causing pain.

Diagnose

Have dysentery syndrome, change in stool shape, or just have stool disorder.

There is hypochromia.

Abdominal pain, fever, weight loss.

Rectal examination with globular blood, tumour.

Colonoscopy - sigma in the presence of dysentery syndrome.

Colonoscopy, biopsy for histological examination, colon staining with baryte.

Dukes rankings and prognosis.

Factors for prognosis and staging of colorectal cancer depend on the depth of the tumour, invasion of the intestinal wall, the presence of regional lymph nodes, as well as the distant metastasis of the tumour (TNM). According to the classification of Dukes, colon cancer has 4 stages:

Stage A (T1N0M0): Superficial, non-invasive lesion of the muscle layer or regional lymph nodes.

Stage B: Lesions invade deeper, but not to regional lymph nodes.

B1: T2N0M0. Injury is limited to the muscle layer.

B2: T3N0M0. Lesions invade the serosa

Stage C: TxN1M0. There are regional lymph nodes.

Phase D: TxNxM1. There are liver, lung, and bone metastases.

Metastasis of colon cancer usually by the portal vein to the liver is the most common and is the first metastasis, rarely seen metastasis to brain lung, adrenal ganglion without metastasis to liver. The exception is that when the cancer is located far from the rectum, the cancer cells can follow the adjacent venous plexus that lives to the lungs and the supernovae without reaching the liver through the portal vein system. 50% of people can live up to 6 to 9 months when liver metastases (large liver, abnormal liver function) are detected or 20-30 months when there are small nodules in the liver with increased CEA and abnormalities on CT scan.

Classified by TNM:

T (tumour) denotes the penetration of the cancer into the colon wall, numbered from T1 to T3, where T1 remains in the mucosa while T3 penetrates the serosa.

N (nodule) indicates whether regional ganglion is affected.

M (metastases) metastasis or not.

Table 1: Ranking by TNM

Stage

 

% live 5 years

Dukes

TNM

Number

A

T1N0M0

I

Tumours confined to the mucosa and submucosa

90

B1

T2N0M0

II

The tumour spread to the muscle class

85

B2

T3N0M0

II

Tumours spread to or through the serosa

70-80

C

TxN1M0

III

Tumours affect the nearby lymph nodes

35-65

D

TxNxM1

IV

Distal metastases (liver, lung ...)

5

Preventive

Preventive Chemistry

Aspirin and NSAIDs: Inhibiting the cell proliferation by inhibiting prostaglandin synthesis. It reduces the risk of colorectal cancer and cancer mortality.

Folic acid and calcium: Reduce the risk of colorectal cancer as polyps.

A diet rich in antioxidants such as vitamins C and A found in fruits and vegetables lowers the rate of colorectal cancer, especially for people with benign polyps.

Oestrogen replacement therapy for postmenopausal women also reduces the risk of colorectal cancer by reducing the synthesis of IGF-1.

Screening tests

Colorectal cancer screening program aims to detect cases of superficial and local cancers early in people who have no symptoms. This screening program is important for people over 40 years of age, with a family history of first-generation illness, and in people with polyps.

Routine tests are rectal exam, gynaecological examination for women over 40 years old and prostate in men and by ultrasound. This job is done every 3 to 6 months and is a means of turning money.

Stool blood: The test has a limited number, only positive about 50% of colorectal cancer because bleeding often occurs in waves and sometimes false positive, So when there is hidden blood (+) then additional tests such as colonoscopy or complete colonoscopy or baryte staining should be done.

Sigmoidoscopy: When there is hidden blood in the stool (+).

Complete colonoscopy: When there is an ejection habit disorder.

CEA every 3 months for people at high risk.

The American Cancer Society recommends annual stool blood testing and rectal sigmoidoscopy every 5 years starting at age 50 in asymptomatic people without risk of colorectal cancer. A complete colonoscopy or double enantiomy colonoscopy performed every 10 years can replace sigmoidoscopy and stool blood tests.

Finding an APC tumour suppressor gene mutation (adenomatous polyposis coli) in the stool is an ongoing test.

Differential diagnosis

Colon Amoeba

The sigmoid and sigmoid colon are two common places where amoeba tumours are common: benign properties of the tumour on baryte staining film with the expression that the tumour is round or oval, concentric narrow, and regular. Diagnosis by endoscopy and biopsy, trial treatment.

Tuberculosis of the cecum

Usually secondary to pulmonary tuberculosis. clinical signs of tuberculosis, diarrheal or alternating constipation, interstitial colic with semi-obstructive colic, palpable right pelvic fossa, IDR (+), baryte There was a regular narrow picture and loss of van Bauhin function, colonoscopy showed a picture of ulcerative lesions with leprosy necrosis in the cecum.

Crohn's disease, colon

The disease has many progression episodes, lasting for many years, with secondary disorders manifesting signs of ectopic symptoms such as biliary tract, joints, mouth ulcers. Characteristics on baryte-dyed colonic film give a thread-like appearance. Diagnosis is confirmed by endoscopy biopsy in the presence of giant epithelial cells.

Ulcerative rectal bleeding

Autoimmune disease, usually occurring in men, between the ages of 20 and 40. Clinically, there is intermittent fever in the advanced stage with joint pain and fresh blood flow. Endoscopy shows shallow ulcers that spread throughout the colon and rectum, biopsy shows only inflammatory cells without dysplasia.

Other types of colon cancer

Colon Lymphoma

Primary colon lymphoma accounts for only about <0.5% of malignant forms of the colon, an increase in Sjogren's syndrome, Wegener's granulomatous disease, rheumatoid arthritis, systemic lupus erythematosus, and immunodeficiency syndrome acquired translation.

Clinically manifested symptoms of nonspecific pain, weight loss, constipation and gastrointestinal bleeding. Colonoscopy reveals isolated tumour lesions or diffuse infiltrative lesions. About 50% of lesions are located in the ileum, 50% are accompanied by malignant lymph nodes. Diagnosed by endoscopy biopsy. The prognosis is also bad, with only 40% living for 2 years.

U carcinoid

Most commonly in the appendix, it is sometimes detected as asymptomatic rectal polyps and up to 25% of rectal carcinoids show bleeding. Carcinoids of the rectum and appendix rarely metastasize. Other areas are less common and often cause narrowing and bleeding and often metastasis. The likelihood of malignancy of carcinoids is high.

Treatment

Treatment of colon and rectal cancer is mainly surgery. Radiation and chemotherapy are often of a supportive nature and can be administered concomitantly or after surgery.

Treatment effectiveness depends on the stage of disease detection when indicated for surgery as well as follow-up and additional treatment after surgery. In addition, it depends on a number of factors that influence the development of cancer, commonly known as risk factors.

Surgery

Surgery to remove colorectal cancer when found is almost an excellent indication

for. Chemotherapy and radiation are just as supportive. However, before surgery, it should be done

Complete colonoscopy when feasible: Purpose to detect cancers or cancer-prone polyps in other areas of the colon.

Enumeration of embryonic-derived carcinogenic antigens (CEA: Carcinoembryonic antigen), a marker of colorectal cancer, for staging and with a postoperative care and follow-up program.

CT scanner: Not directly useful for colon positioning and surgery, but can help detect minor liver metastases that may be missed by ultrasound.

Endometrial ultrasound: Is a new ultrasound technique, helping to examine the pelvic area and evaluate the stage of rectal cancer.

The aim of surgery is to extensively remove the affected intestinal area and also the lymphatic drainage and blood vessels supplying that area. Cut intestine included

5cm above and below the area affected by the tumour, may in some cases be wider, to include the entire area provided by a blood vessel constricted during surgery. However, even with broader cut, the prognosis is not better than with moderate cut. In the case of the rectum, when it is necessary to preserve the anal sphincter, the lower part can be cut off just 2 cm from the affected area.

Surgery is also indicated even when there are distant metastases, because it can reduce the symptoms of bleeding, intestinal obstruction, abdominal pain, and improve the quality of life of the patient in the remaining days.

Follow-up after surgery: The rate of cancer recurrence after each surgery depends on the stage of the disease. Frequent cancers often have a higher rate of recurrence. Patients with genetic risk factors are more likely to recur. Oral cancer is also another risk when the cut area is not enough to remove all malignant cells that cannot be seen with the naked eye. Therefore, follow-up after each operation is required.

Periodic examination is the most effective method of monitoring. If the colonoscopy has not been done before the surgery, this procedure should be performed after a few months. Patients should be followed up at least twice a year with endoscopy (preferably), X-ray or abdominal ultrasound. High-risk cases may be 3 times a year because the risk of recurrence of cancer or adenocarcinoma polype (cancer risk) may be 3-5% (for cancer) and 15% (for polype).

Radiotherapy

Pelvic radiolysis has additional indications after rectal cancer removal surgery, especially when the tumour has penetrated the serosa because despite extensive resection, usually, the tumour can already spread early to the area. This is due to the very rich lymphatic system. Radiation therapy, whether before or after surgery, prevents pelvic metastasis, but does not prolong the patient's life. Radiation therapy before surgery, when cancer has spread, is large, may not be completely removed. however, radiation therapy alone cannot cure colorectal cancer.

Chemotherapy

Chemotherapy alone is of limited effectiveness, so it is often used as an adjunct to surgery. The most effective so far remains the 5-FU. Can be used alone or in combination with a number of other drugs. Effective only 15-20% of tumour size reduction in 50% of cases (partially effective).

In the case of liver metastases, the introduction of 5-FU directly into the tumour via the hepatic artery is more efficient than the peripheral vein infusion, but is more expensive and also more toxic while the patient's life is no longer.

Combining 5-FU with folinic acid (also known as leucovorin factor or citrovorum) improved 5-FU's effectiveness by up to 3 times, but toxicity also increased.

Specific dosage:

5-FU 425mg / m2 TM (5 ') + Ca-folinate 200mg / m2 TM. Use from 1-5. Day 29, repeat the course. Just enough 6 cycles

The case of liver metastasis alone, not accompanied by other regions may have an indication for partial hepatectomy because the 5-year survival rate accounts for 20-30%.

Combining surgery with radiotherapy, chemotherapy is well evaluated in patients in stage B or C, as an eradication measure in the absence of metastases. An author also used levamisole, an anthelmintic and immunomodulatory effect, which could reduce the likelihood of recurrence by 40%, but not to prolong life for more than 5 years compared to not taking levamisole.

Immunotherapy

The monoclonal 17-1A edrecolomab antibody (Panorex) is being tested. Results of multiple trials have shown better efficacy than 5 FU chemotherapy alone or in combination. The greatest advantage of immunotherapy is that it can further destroy the remaining cancer cells. Currently people are testing for K colorectal phase II (DukesB2 / B3). Side effects of immunotherapy include an allergy to mouse protein, vomiting, nausea, and diarrheal.

Prevention

Diet: Low animal fat, high fiber (controversial).

Medicines: Aspirin and other non-steroid anti-inflammatory drugs (NSAIDs) have been shown to be effective, reducing the risk of colorectal cancer.

Antioxidants such as vitamins C and E were once mentioned, but there is no evidence.

Oestrogen for menopausal women may reduce the risk of colorectal cancer in these people.

Screening regimen for high-risk subjects (with relatives, especially relatives type 1) with colorectal cancer. Most effective is a colonoscopy every 2 or 3 years. CEA can be quantified every 3 months. It is simpler than a check every 3-6 months with rectal, vaginal, and abdominal ultrasound. Fecal occult blood monitoring has low sensitivity and specificity, so it is rarely used, although this method is easy to perform and inexpensive.