Release date: 2014-03-03
At present, digestive system tumors such as esophageal cancer, gastric cancer and colorectal cancer have become clinically high-risk diseases. Early diagnosis and early treatment are of great significance for prolonging patient survival time and reducing mortality.
Fecal examination is an effective means of clinical testing and the most commonly used method of census. It is simple, easy to use, low cost, non-invasive and suitable for large-scale population screening. With the development of molecular biology, the early screening of gastrointestinal tumors for fecal examination has attracted increasing attention.
Fecal hemoglobin combined with transferrin to detect fecal occult blood is one of the most widely used and most evaluated trials in gastrointestinal cancer screening, and has the advantages of being quick and simple, painless, and easy to use repeatedly. For patients who have been tested positive for multiple fecal occult blood tests, gastrointestinal tumors should be further investigated regardless of age or gender.
It has been reported that the positive rate of fecal occult blood test in peptic ulcer is 40% to 70%, which is intermittently positive. The positive rate of cancer in digestive tract (such as gastric cancer) can reach 95%, which is persistently positive. Gastrointestinal hemorrhage caused by various other diseases can be positive.
Hemoglobin (Hb) in the fecal occult blood test can detect bleeding in any part of the lower digestive tract, while transferrin (Tf) can detect bleeding in the upper digestive tract. After the hemorrhage of the upper digestive tract is digested by the digestive enzyme, the red blood cell matrix is ​​digested, and the hemoglobin no longer has an immune response. Transferrin is mainly present in plasma, is almost absent in the feces of healthy people, and is abundant in feces during gastrointestinal bleeding. The stability of transferrin is significantly higher than hemoglobin and is not easily destroyed by digestive enzymes. For upper gastrointestinal bleeding, detecting Tf while detecting Hb can reduce the occurrence of false negative results. Simultaneous detection of both antigens by two immunological methods can complement each other.
Fecal calprotectin detection Calprotectin (CPT) was first isolated from neutrophils by Fagerhol in 1980 and was named L1 protein, which was later named for its structure containing calcium and antimicrobial properties. Non-covalently bound by two heavy chains 14 and one light chain 8 form heterodimers, each of which can bind two calcium ions; and has the ability to bind zinc ions and have heat resistance. Calprotectin is a heterozygous calcium-binding protein that has anti-protease activity in the presence of calcium ions, remains stable in the intestinal lumen and the environment for a long time, and is not destroyed by various enzymes and bacteria; it is a neutral granule. Important proteins in cells and activated macrophage cytoplasm can be used as markers of acute inflammatory cell activation; they are extremely stable in feces and superior to previous fecal markers. Foreign studies have shown that the content of calprotectin in feces is significantly increased during UC activities, which can dynamically reflect the changes of UC activity. The histological changes in active phase show the characteristics of acute and chronic inflammation. Neutrophils are considered to distinguish acute UC. A key indicator with chronic inflammation. Calprotectin is 55% sensitive to adenomas, while FOB is only 10% sensitive to adenomas. Calprotectin detection is of higher value for early detection of adenomas, since the malignant phase of adenomas is 5- In 7 years, adenoma is the only tumor that can be detected before malignant transformation. The detection of calprotectin is extremely important.
Fecal calprotectin is very stable in feces, and the test can accurately distinguish between intestinal and functional diseases of the intestine, and it also has high accuracy in identifying IBD and colorectal cancer. Compared with colonoscopy, it has the advantages of simplicity, economy, non-invasiveness, etc., to a certain extent, it can avoid the pain of colonoscopy and make up for the insufficiency of patients to review at any time. Compared with fecal occult blood, fecal calprotectin can be quantitatively detected, and early non-hemorrhagic lesions can be found, and the results are not affected by systemic conditions, dietary components, general medications, and nutritional support treatment. It is of great guiding significance to monitor the condition of the confirmed cases and evaluate the efficacy of the drugs.
Fecal carcinoembryonic antigen (CEA) was used to detect the increase in fecal CEA in patients with digestive tract tumors, and the benign disease of the digestive tract was not elevated. Serum CEA has little value in the diagnosis of colorectal cancer, and fecal CEA has significant changes in patients with intestinal cancer.
Li Yongming published in the "Cancer" study results: with a critical value of 5 micrograms, fecal CEA diagnosis of colorectal cancer, the positive rate of 76.9%, false positive rate of 12.8%. Fecal CEA is a good indicator of gastrointestinal tumor screening, superior to serum CEA and FOB (International Journal of Oncology).
Jiang Tao reported CEA and TAG-72 combined detection of colorectal cancer sensitivity of 80.11%, specificity of 70.59%, accuracy of 81.13%, false positive rate of 29.41%, and false negative rate of 13.8%. Conclusion CEA and TAG-72 combined detection in feces Helps early diagnosis of colorectal cancer and increases sensitivity and specificity.
Fecal Helicobacter pylori antigen detection Fecal Helicobacter pylori antigen detection compared with breath test, no isotope contamination, low cost, easy to operate, the elderly and infants can also check, have a guiding role in treatment.
The serological method is used to detect the antibody level. Since the serum antibody remains in the long-term after radical treatment, it can not reflect the current infection of Hp, and can not be used for the observation of curative effect.
Raguza used this method to evaluate 133 children in developing countries. The sensitivity and specificity of HpSA detection in adolescents was over 90%. The rapid detection of HpSA in China was performed on 62 patients before anti-Hp treatment (pre-treatment group). The stools of 42 patients who underwent anti-Hp treatment (post-treatment group) showed that the sensitivity and specificity of the pre-treatment group were 100% and 92%, respectively. The sensitivity and specificity of the group after treatment were 93. % and 81%; the total sensitivity and total specificity of 104 patients were 97% and 88%, the coincidence rate was 91%, the positive predictive value was 83%, and the negative predictive value was 98%.
Detection of other tumor markers in feces Adnab.9 is a monoclonal antibody whose elevation is an antagonistic response to adenoma cell membrane antigens. Adnab.9 is present in the neoplastic epithelium of the colon, and staining indicates that it is likely to progress to colorectal cancer in the future." Using the enzyme-linked immunosorbent assay to detect the diagnostic value of Adnab.9 in colorectal cancer, the positive rate of Adnab.9 in 63 patients with colorectal cancer was 63% (including 59% of colorectal cancer and 83% of adenoma). ), inflammatory bowel disease 33%, hyperplastic polyps 0, control group 10%. Therefore, Adnab.9 is a promising marker for colorectal cancer screening, especially for adenomas.
Most human somatic cells do not express telomerase; in malignant tumors, telomerase can be reactivated to make cells immortalized. Luo Chengyu et al 120 studied the expression of telomerase activity in fecal exfoliated cells of 43 patients with colorectal cancer. The results showed that 62.8% of patients with colorectal cancer were positively expressed, and there was no significant correlation with Dukes stage, lymph node metastasis and tumor site; fecal telomere The sensitivity, specificity and positive predictive value of enzyme detection were 62.8%, 95.7% and 96.4%, respectively. It is suggested that detecting telomerase activity in exfoliated cells may be a new method for screening colorectal cancer.
The increased expression of cyclooxygenase-2 (COX-2) in colon cancer tissues is associated with tumorigenesis, progression and metastasis. Kanaoka et al. detected COX-2 mRNA and CEA mRNA in feces, and the COX-2 mRNA sensitivity and specificity were 90% and 100%, respectively. CEA mRNA sensitivity and specificity were 100% and 5%, respectively. COX-2 mRNA was detected in 3 patients with DukesA or 3 patients, 14 patients were detected in 14 cases in stage B, 11 cases were detected in stage C or D stage; 7 cases were detected in 7 cases of proximal colorectal cancer, 22 cases were far Twenty-one cases of colorectal cancer were detected, indicating that COX-2 mRNA is superior to CEA mRNA, and is independent of tumor size, grade and location. It is suggested that fecal COX-2 detection has a high sensitivity and specificity for colorectal cancer, and it can be used as a promising marker for screening colorectal cancer, but a large sample is needed for evaluation.
Tumor M2 pyruvate kinase (TumorM2pyruvateki–nase, TUM2.PK), as an isoenzyme of pyruvate kinase, is mainly present in tetramers in normal cells; in tumor cells, due to anabolic needs, M2–PK is abundantly expressed and converted to exist mainly in the form of dimers, and this dimeric form of M2–PK is called TUM2.PK. Ewald et al reported that stool TUM2–PK detected colorectal cancer sensitivity of 77.9% and specificity of 74.3% to 83.3%. The adenoma sensitivity was 45.9%, and if the adenoma diameter was >1 cm, its sensitivity increased to 61.1%. In addition, Vogel et al. compared chemical FOBT, immunological methods FOBT and TUM2–PK for colorectal cancer, and found that although TUM2-PK was less specific (89%, 94% and 72%, respectively), Sensitivity (48%) was significantly higher than the other two (10% and 19%, respectively). Recently, Tonus et al. studied TUM2–PK in feces and found 39 of 42 patients in the control group < 4.0 KU/L (specificity 93%). The median concentration of TUM2–PK in the experimental group was 23.1 KU/L for colon cancer, 6.9 KU/L for rectal cancer, and 14.7 KU/L for colorectal cancer. The difference was statistically significant and correlated with tumor Duke's stage and TNM classification. Diagnosing the overall sensitivity of colorectal cancer by 78%, and increasing from 60% of T1 to 100% of T4, from 60% of Duke'SA to 90% of Duke'SD, so the TUM2.PK test in feces is screening for colorectal cancer. A suitable indicator.
DNA Testing:
Early detection of tumors is the key to improving the five-year survival rate of cancer patients. People have been working to find diagnostic methods that can be used for monitoring and screening high-risk groups. With the development of molecular biology, people realize that the occurrence and development of tumors are attributed to related gene mutations, and the exfoliated cells in feces contain mutation genes closely related to colorectal cancer. Gene detection in feces is expected to be a screening diagnosis for colorectal cancer. New method.
A foreign company developed a Stool-based DNA (sDNA) screening test for detecting DNA markers associated with colon cancer. The data of 10,000 clinical trials showed that the sensitivity of colon cancer detection was 92%, the sensitivity of detecting precancerous polyps was 42%, the sensitivity of polyps more than 2 cm was 66%, and the specificity of all clinical data was 87%. .
In summary, stool examination has the characteristics of non-invasive, simple and economical, especially the low cost of immunological examination and high detection rate, which will become the mainstream direction of routine examination of gastrointestinal tumors in the future; fecal DNA examination has a higher Sensitivity and specificity, if further improved in automation, and more intimate in the cost of testing, will become an indispensable means of detection in the future. Fecal analysis has an extremely promising future in gastrointestinal tumor examination.
Source: Medical Device Innovation Network
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