Early diagnosis of esophageal cancer

  Esophageal cancer is one of the common malignant tumors of digestive tract in China and ranks 6th among malignant tumors in the world. In view of the insidiousness and non-specificity of its early symptoms, most of the patients diagnosed and treated clinically are already in the middle or late stage. The prognosis of early esophageal cancer is very different from that of middle and late stage esophageal cancer. Early diagnosis of esophageal cancer is an effective way to improve the treatment effect of esophageal cancer. The methods of early diagnosis of esophageal cancer are introduced as follows 1.Barium X-ray meal imaging or gas-barium double imaging Barium X-ray meal imaging is the most common and basic imaging method to show esophageal lesions in clinical practice, and gas-barium double imaging is especially sensitive to detect early micro lesions. It can not only show mucosal lesions and tumor length better, but also dynamically observe the movement of the tube wall and show the relationship between the esophagus and the surrounding tissues. For early micro lesions, careful observation of mucosal fold changes in multiple directions can clearly show where the lesions are located, but the accuracy rate of imaging examination is only 42.0%, therefore, the diagnosis of early esophageal cancer cannot rely on X-ray examination alone yet.  2.Esophageal mesh cytology examination Esophageal mesh method has been one of the main examination methods for census in high incidence area of esophageal cancer in China because of its simplicity, practicality and high accuracy. With the application of liquid-based cytology and automatic cytology analysis system, the sensitivity of esophageal screening method in diagnosing esophageal cancer has been improved. However, this method is difficult to be used as a screening tool in the general population because it is more painful for the subject. After more than half a century of practice, it has been found that the acceptance rate of esophageal stretching method is decreasing in high incidence areas. Compared with endoscopy, the former has a 30% to 50% missed detection rate. Therefore, in recent years, endoscopy is being gradually applied to the screening of high-risk groups.  3.Application of endoscopy in diagnosis of esophageal cancer Electronic endoscopy can directly observe the cancer tumor, visually observe the mucosal changes and clamp the tissue for pathological examination, so it is the main diagnostic tool for esophageal cancer nowadays, and its accuracy rate of diagnosing early esophageal cancer can reach 70.0% to 90.0%. However, it lacks a holistic view of esophageal examination and cannot visually show the peristalsis, dilatation and other morphology of the esophageal wall as well as the changes of the wall edges.  In recent years, scholars at home and abroad have advocated the application of pigmented endoscopy or ultrasound endoscopy for the diagnosis of early esophageal cancer in order to improve the sensitivity and accuracy of microscopic examination. With the combination of other techniques and endoscopy, some new examination methods have been developed, which have significantly improved the detection rate of early esophageal cancer.  Ultrasound endoscopy (EUS) has been applied to the diagnosis of early esophageal cancer in recent years, which is an examination method combining endoscopy and ultrasound technology. EUS can distinguish the 5-layer structure of esophageal wall, determine the level of infiltration of esophageal cancer, the depth of outward expansion and the presence of mediastinal, lymph node or intra-abdominal organ metastasis, etc., so as to improve the dual diagnosis level of endoscopy and ultrasound. ~The accuracy is 89%~92% and 59%~60% respectively.  The staining of Lugol solution for esophageal squamous carcinoma and precancerous lesions is mainly based on the fact that glycogen in esophageal mucosal squamous epithelial cells appears brownish-yellow when exposed to iodine, while glycogen content in carcinoma and atypical cells disappears or decreases significantly, and the iodine staining shows the original color of iodine or different degrees of light staining, and the boundary is often very clear. The boundary is often very clear. Biopsy in unstained areas can improve the detection rate of lesions. The sensitivity of combined iodine staining and biopsy is 95% to 100%, which greatly reduces the rate of missed diagnoses. The extent of cancer can be further determined by the color image characteristics of the unstained area based on its hue, depth, visual perceptual properties and margin status. However, it is prohibited for iodine allergy, in addition, a few people can cause retrosternal pain, abdominal pain, nausea, vomiting, etc. 3, 1, 1, Lugol’s fluid staining method Japanese scholars first used Lugol’s fluid staining for the diagnosis of early esophageal squamous carcinoma. Normal esophageal squamous epithelial cells are rich in glycogen and can appear brownish after contacting with Lugo’s fluid, while abnormal squamous epithelial cells stain lighter or not after encountering Lugo’s fluid due to the reduction or disappearance of glycogen content, and the boundary is often very clear. This method can improve the accuracy of endoscopist’s sampling and the diagnosis rate of early esophageal cancer.  3.1.2 Methylene blue staining method Compared with esophageal squamous carcinoma, methylene blue staining is mainly used for the early diagnosis of esophageal adenocarcinoma. The basic principle is that normal esophageal squamous epithelial cells do not take up methylene blue and do not stain, but can be taken up by enterocytes and columnar cells or combined with white moss and necrotic material on the surface of erosion, ulcer or cancer and stained blue.  3. 1. 3.Double staining method The main double staining methods for diagnosing early esophageal cancer are: methylene blue 2 Lugol’s solution staining method and toluidine blue 2 Lugol’s solution staining method. The blue zone is malignant tumor, the tan zone is normal esophageal mucosa, and the area between the two colors is cancer infiltration zone. The double staining of toluidine blue 2 Lugo’s solution has some significance in evaluating the depth of infiltration of the lesion. The staining was light blue when the lesion was confined to the epithelial layer, blue when the lesion infiltrated into the muscular layer of the mucosa, and blue-black when the lesion infiltrated into or beyond the submucosa. It can be seen that the endoscopic double staining method is helpful for the diagnosis of early esophageal cancer, superficial cancer and precancerous lesions. 3.1.4 Laser fluorescence detection method After the patient takes orally or injects fluorescent substance, a laser of certain wavelength is used to observe through the endoscope, and if there is tumor in the tissue, fluorescence can appear, so that the diseased tissue can be clearly displayed. Commonly used fluorescent photosensitizers are hematoporphyrin derivatives (D), acridine orange (AO), methyl blue dye, etc. Commonly used lasers are Ar+, Kr+, N2 or Xe+, etc. Fluorescence technology is of high value for the diagnosis of precancerous lesions, carcinoma in situ, submucosal carcinoma and multiple lesions, but its sensitivity is not as good as pigmented endoscopy, and it is prone to false positives in ulcers and inflammatory lesions, and its resolution is low, which limits its application in clinical practice.  4.Application of CT and MRI in the diagnosis of esophageal cancer CT and MRI examination can help to show the thickness of esophageal wall, the extent of intramural infiltration, the degree of involvement of surrounding tissues and metastasis, etc., but they cannot observe the mucosal lesions and the peristalsis of the wall, so they are generally used as supplementary examinations to determine the surgical plan and radiotherapy plan after screening.  5.Research on molecular level tumor markers Tumor marker detection is an important tool for early diagnosis of malignant tumors. How to correctly select the appropriate markers or marker groups for esophageal cancer is the key to early diagnosis of esophageal cancer. It has been found that the genes that may be related to malignant transformation of esophageal mucosa mainly include p53, cyclinD1, p16, Ras gene and so on.  Serum tumor markers have been widely used in clinical practice, such as AFP and CEA in liver cancer and colorectal cancer, because they are easy to detect, less traumatic to patients and can reflect changes in disease in time. In the area of esophageal cancer, we have also conducted in-depth research, and now we have squamous cell carcinoma antigen (SCC-Ag), carcinoembryonic antigen (CEA), anti-p53 protein antibody (p53-Ab), glycocalyx antigen 19-9 (CA19-9), cytokeratin 19 fragment (CYFRA), and CEA. In conclusion, early diagnosis of esophageal cancer is of great significance, but there is no simple and effective diagnostic method, especially for population screening, so there is a long way to go in the research of early diagnosis of esophageal cancer. However, serum markers are simple and non-invasive, and if there is a breakthrough in accuracy, it may significantly improve the early diagnosis rate of esophageal cancer and ultimately reduce the death rate of esophageal cancer patients.