Introduction:
Esophageal cancer is a common malignant tumor in humans, accounting for 2% of all malignant tumors, accounting for more than 90% of esophageal tumors. It ranks second only to gastric cancer in retrospective investigation of all malignant tumor deaths. It is estimated that about 200,000 people die of esophageal cancer every year in the world. China is a high-risk area for esophageal cancer, and it is one of the most common malignant tumors that are extremely harmful to people's lives and health. The age of onset is more than 40 years old, more men than women. However, in recent years, the number of people under the age of 40 has a growing trend. The occurrence of esophageal cancer is related to chronic nitrosamine stimulation, inflammation and trauma, genetic factors, and trace element content in drinking water, food and vegetables. But the exact reason is not clear and needs to be studied.
Cause:
(1) Causes of the disease
The high-incidence area of esophageal cancer indicates that the area has the conditions for its occurrence, such as the presence of strong carcinogens, carcinogens, lack of some anti-cancer factors and genetic susceptibility. However, the results of studies in various countries are very inconsistent, reflecting the diverse causes of esophageal cancer. Western scholars believe that smoking and drinking are the main reasons. In the high-incidence area of Lin County, China, because of poverty, residents drink alcohol for nearly one or two decades.
At present, although the etiology of esophageal cancer is not fully understood, in recent years, the etiology of esophageal cancer has been explored in many ways. From nitrosamines, nutrients, trace elements, fungi and viruses, genetics and many other aspects, research and exploration at multiple levels have made significant progress. It is generally believed that the occurrence of esophageal cancer may be the result of a combination of various factors, and the factors related to the incidence of esophageal cancer are as follows:
1. Living habits and chronic stimulation of esophagus
(1) Smoking and esophageal cancer: Western scholars believe that smoking may be the main cause of esophageal cancer. Epidemiological investigations have found that smoking in some high-risk areas of esophageal cancer is quite common. In some areas, residents do not smoke, and esophageal cancer is rare. For example, Paymaster reported that Indian Muslims, Christians, and Hindus who love sapphire leaf tobacco and chewing betel leaves have a high incidence of esophageal cancer, and esophageal cancer among the devotees without this hobby is rare. Therefore, it is believed that smoking may be the cause of the high incidence of upper esophageal cancer and mid-stage cancer. However, the previous epidemiological survey in China did not find that smoking is closely related to the occurrence of esophageal cancer. It seems that most of these studies have come from local high-incidence areas of esophageal cancer and are limited to the rural population. In recent years, Chinese scholars have conducted a large number of epidemiological investigations on high-incidence areas, low-incidence areas, and urban and rural esophageal cancers. Most of them still believe that smoking may also be a cancer-promoting factor in the development of esophageal cancer in China. Many studies have shown that tobacco is a carcinogen, and its harm to the human body is multi-effect. The carcinogen in tobacco may be swallowed to the esophagus with saliva or food or absorbed into the esophagus to cause cancer. It has been found that cigarette smoke and tar contain various carcinogens, such as polycyclic aromatic hydrocarbons such as benzo-α oxime, epoxides, lactones, peroxides and halogen ethers, and also contain various nitroso compounds such as arylene. Nitropyrrolidine, dimethyl nitrosamine, nitroso-nornicotine or nitroso-nicotine. In addition, there are a large number of alkanes and alkoxy radicals formed by the reaction of NO, NO2 and hydrocarbons in the smoke. These components can directly attack the fat, protein and nucleic acid components of the cells, causing cell damage and causing cancer. Several chemicals in tobacco were added to drinking water to feed Fisher rats for 30 weeks. As a result, 12/20 cases of esophageal tumors were found in rats with nitroso-nor-nicotine, and 3 of them were esophageal cancer, which further confirmed tobacco. Relationship with the occurrence of esophageal cancer.
(2) Alcohol and esophageal cancer: the relationship between esophageal cancer and drinking. Foreign scholars have done a lot of epidemiological investigations. They found that many patients with esophageal cancer have a lot of drinking history, or most of them are brewers and staff related to wine merchants. Recently, British and Hong Kong scientists surveyed smoking and drinking in patients with esophageal cancer in Hong Kong. After thorough analysis, it was found that drinking alcohol may cause esophageal cancer more easily than smoking. Domestic scholar Zhang Yude et al investigated 1400 patients with esophageal cancer and found that the case group had a positive drinking history (average white wine more than 2 or more for 5 consecutive years), accounting for 26.9%, while the control group was 17%. However, Liu Boqi et al. conducted case-control on esophageal cancer patients in Yangzhong County of Jiangsu Province, Xinyuan County of Xinjiang, and Huai'an County of Jiangsu Province, and found that only Huai'an County, which has a large drinking capacity, is a positive result. It seems that the role of alcohol has a certain relationship with its duration and the amount of alcohol consumed. However, there is no report on the induction of esophageal cancer in animals by alcohol or alcoholic products. The more accepted view is that the wine itself may not be directly carcinogenic, but it has a cancer-promoting effect. Alcohol can act as a solvent for carcinogens, promote carcinogens to enter the esophagus, cause damage to the esophageal mucosa, and create conditions for the occurrence of esophageal cancer. Some studies at home and abroad have found that some wines may be contaminated with nitrosamines, polycyclic aromatic hydrocarbons, phenolic compounds, DDT, and the like. These contaminants may enhance the damage of alcohol to the esophageal mucosa.
(3) Eating habits and esophageal cancer: After investigation of the incidence factors in high-incidence areas, it was found that patients with esophageal cancer had the habit of thick food, paste, eating too fast, and eating hot drinks. These factors damaged the esophageal epithelium and increased carcinogenicity. Sensitivity of matter. Most studies have shown that hot food is one of the pathogenesis factors of esophageal cancer. In China's high incidence of esophageal cancer, many residents and esophageal cancer patients have a good habit of eating hot. The researchers measured the temperature of the food in the bowl when the residents in the high-incidence area were eating, and found that it can be as high as 70-80 ° C and the highest is 80-88 ° C. It has been reported that mice fed with hot water at 75 °C can be found that epithelial cell degeneration, mucosal inflammation and cellular nucleic acid metabolism are affected, so long-term repeated thermal stimulation may promote the carcinogenesis of the esophagus. There are also reports that eating too fast, food is rough, eating and drinking, and drinking tea, and meals are not related to esophageal cancer.
Kazakhs love to chew "Nas", which is very irritating and contains tobacco. In Japan, people who like to eat hot porridge have a higher incidence. Excessive long-term drinking of strong alcohol and a large number of smokers may be an important cause of esophageal cancer in European and American homes.
(4) Chronic stimulation of esophagus: Some of the pathogenic factors mentioned above will cause irritation to the esophagus, and long-term repeated stimulation will further lead to esophageal mucosal lesions. Studies have found that certain esophageal lesions, such as esophageal achalasia, chronic esophagitis, benign esophageal stricture and esophageal leukoplakia, have a higher incidence of esophageal cancer, indicating chronic damage and inflammation caused by chronic irritation in the incidence of esophageal cancer It plays a role.
2. Nutritional factors and trace elements In recent years, Chinese scholars have done a lot of nutrition investigation and nutrition intervention experiments at some sites of esophageal cancer prevention and treatment.
Among them, the Sino-US cooperation in the Linxian County of Henan Province, which has been in the past 14 years (the Chinese Academy of Medical Sciences and the National Cancer Institute NCI) research project, has achieved a series of phased results, which have been produced at home and abroad. Tremendous influence. The study found that nutritional deficiency is a common phenomenon in high-risk areas of esophageal cancer, vitamin A, C, E, riboflavin, niacin, animal protein, fat, fresh vegetables, fruit intake are low. Many reports indicate that the lack of meat, eggs, vegetables and fruits can increase the risk of esophageal cancer. Chinese and American scholars have found that supplementing a diet rich in high protein, vitamins and minerals can protect the body and prevent esophageal cancer. Tests have shown that fresh vegetables, fruits, tea, and vitamins have anti-mutation effects, and the relative lack of risk factors should be considered as esophageal cancer. Recently, some scholars have found that feeding corn with pure corn feed can significantly increase the carcinogenic rate of methylphenylnitrosamine, suggesting that nutrient deficiency can increase the sensitivity of esophageal epithelial cells to nitrosamine carcinogens. Some animal experiments have also confirmed that the lack of vitamins A, C, E, and riboflavin can promote esophageal lesions and enhance the role of carcinogens in the esophagus. In-depth analysis found that vitamin C can block the synthesis of carcinogenic N-nitroso compounds, riboflavin deficiency can significantly increase the induction rate of methylbenzylnitrosamine in rat esophageal cancer, and shorten its latency. This further reveals the mechanism by which vitamins fight cancer. Lin County's research results show that supplementation of riboflavin and niacin compound nutrients to high-incidence areas may reduce the incidence of esophageal cancer. Therefore, supplementing vitamins in high-incidence areas may be an effective preventive measure.
The relationship between trace elements and tumors has attracted more and more attention. The investigation confirmed that the content of trace elements such as molybdenum, selenium, cobalt, manganese, iron, nickel and zinc in water and soil in high-incidence areas of esophageal cancer is low. The lack of molybdenum has received more attention and is considered to be a factor in the pathogenesis of esophageal cancer. Molybdenum is low in nature and unevenly distributed. The serum molybdenum test in some high-incidence areas showed an average of 2.2-2.9 ng/ml, which was significantly lower than the mean value of serum molybdenum (4.8-5.9 ng/ml) in non-high-incidence areas. Molybdenum is a component of plant nitrite reductase. Molybdenum deficiency can accumulate nitrite in the environment and crops, while application of molybdenum fertilizer can increase the content of molybdenum in food, reduce the content of nitrite, and the intake of molybdenum is insufficient. It can affect the activity and physiological functions of some enzymes, which may be one of the causes of the increased incidence of esophageal cancer. Some investigations have shown that selenium is absent in high-risk areas of esophageal cancer. Selenium has a protective effect on cell membrane peroxidation through the action of glutathione peroxidase, enhancing the body's immune response and resistance to cancer occurrence and growth. Although organic selenium deficiency may not directly cause esophageal cancer, it may increase the susceptibility to carcinogens. Studies on human and environmental zinc deficiency in high-incidence areas have been reported, and zinc deficiency can lead to decreased immunity. Animal experiments show that cadmium has a role in inducing cancer in the esophagus and anterior stomach of mice, suggesting that cadmium may be a risk factor for esophageal cancer. In Lin County, patients with esophageal epithelial hyperplasia supplemented with multi-vitamin mineral compound nutrient solution, found that the epithelial hyperplasia can be reversed, the cancer rate is significantly lower than the control group, indicating that the secondary prevention of drug-blocking esophageal cancer has achieved preliminary good results.
3. Nitrosamine compounds Nitrosamines are recognized as a strong carcinogen. More than a dozen nitrosamines have been shown to induce esophageal cancer in animals, including methylbenzylnitrosamine (NMBAR), sarcosine ethyl nitrosamine (NSAR), nitrosopyrrolidine (NPyr), and Nitroso piperidine (NPip), N-3-methylbutyl-N-1-methylacetonyl nitrosamine (NAMBNA), and the like. Nitrosamines and their precursors are widely distributed in the environment and enter the body through drinking water and food. Its precursor is nitrosated in the stomach to produce nitrosamines. In recent years, it has been found that the nitrate content in the drinking water of Henan Linxian County, Hebei Cixian County, Shexian County, Guangdong Shantou, Shanxi Qufu and Yangcheng in the high incidence areas of esophageal cancer is significantly higher than that in the low-incidence area. According to the investigation, seven volatile nitrosamines were detected in the environment of Linxian County, a high incidence area of esophageal cancer. The high positive rate was dimethyl nitrosamine (64%), dipropyl nitrosamine (30%) and diethyl. Nitrosamine (24%). It was also detected that the cornmeal contained non-volatile sarcosine nitrosamine and the radish strip contained proline nitrosamine. The content of nitrite and nitrate in the contaminated food in Lin County is high. Secondary and tertiary amines are also widely distributed in food and the environment. Under acidic conditions in the stomach, amines and nitrites are easily combined to produce nitrosamines. It is reported that people with high incidence of esophageal cancer have moldy foods, which contain more nitrosamines and precursors. Mold can not only reduce nitrate to nitrite, but also decompose food protein to increase secondary amine content, thereby promoting the synthesis of nitrosamines. Lu Shixin reported for the first time in the world that residents with different esophageal cancer mortality rates consumed different amounts of nitrosamines from the diet. The intake of nitrosamines in the diet was: Lin County (高发)>济源(中高发)>禹县(low hair). The results showed that the amount of nitrosamine intake from the diet was positively correlated with the incidence of esophageal cancer. The total nitrosamine content in the gastric juice of Linxian County was found to be 24.93 ppb in male gastric juice, 20.51 ppb in females and 18% in females, which is the ratio of male to female in the incidence of esophageal cancer in Lin County. Match. The content of nitrosamines in the gastric juice of Linxian County was significantly positively correlated with the lesions of the esophageal epithelium, normal mild hyperplasia, severe hyperplasia and carcinogenesis. Animal experiments have shown that nitrosamines can induce esophageal cancer in animals, and blocking the nitrosation of amines can prevent the occurrence of esophageal cancer. A new nitroso compound, nitrosoisoproline, found in the urine of Linxian County can cause malignant transformation of NIH3T3 cells and inoculate fibrosarcoma in nude mice. In recent years, Lu Shixin et al. used NMBzA found in the environment of Linxian County to co-culture with human fetal esophageal epithelium for three weeks. The epithelium was transplanted into the mesentery of BALB/C nude mice, and NMBzA was used to continue feeding the nude mice. Cancer, no tumor in the control group of nude mice. The presence of the AIu sequence in the DNA extracted from the NMBzA-induced tumor tissue demonstrated that the induced tumor was derived from human tissue. These results demonstrate for the first time that nitrosamines can induce human esophageal epithelial squamous cell carcinoma, providing direct evidence for the etiology of nitrosamines in esophageal cancer in Lin County.
Sauerkraut is a traditional food in China's high-incidence areas of esophageal cancer, Linxian County, Shanxi Yangcheng, Sichuan Yanting, and Jiangsu Yangzhong. In addition to some contaminated fungi, it also found trace amounts of benzo-α and nitrosamines. Contains a nitroso compound called Roussin Red Methyl Ester. About 55% of the sauerkraut in Lin County contains this compound, and the content is between 1 and 5 ppm. Experiments have shown that Roussin red methyl ester can cause malignant transformation of C3H/10T1/2 cells activated by 3-methylcholane. After application of mouse skin, the epidermis can be thickened and the number of sebaceous glands can be reduced. This compound may be present. A carcinogen in sauerkraut. A number of epidemiological surveys have shown that sauerkraut is one of the high-risk areas of both fungi and nitrosamines.
4. The role of fungi and viruses
(1) The role of fungi: Studies have shown that the incidence of high incidence of esophageal cancer in China is related to fungal esophagitis and fungal contamination of food. Through repeated epidemiological investigations in Linxian, Yangcheng, Cixian, Yanting, Nanbromo and Xinjiang areas in Gaofa District, it was found that certain fungi and their metabolites in food, sauerkraut and mildew food are important for esophageal cancer. Risk factors. For example, the carcinogenic effects of aflatoxin B1 have been recognized. Linxian food is often contaminated by Fusarium oxysporum, Alternaria alternata, Penicillium arcuate, Geotrichum candidum, and Aspergillus flavus. These fungi not only reduce nitrate to nitrite, but also break down proteins, increase the amine content in food, and promote the synthesis of nitrosamines. The carcinogenic effect of moldy food has been confirmed by animal experiments. Moldy corneal surface (including Fusarium oxysporum) induced rat esophageal papilloma, gastric papilloma and esophageal cancer, and can cause epithelial hyperplasia and papilloma-like changes in the esophagus and anterior stomach of mice. The content and species of Fusarium oxysporum detected in the grain of Linxian County were significantly higher than those in the low-incidence areas of esophageal and cardiac cancer at home and abroad, and positively correlated with the incidence of esophageal and cardiac cancer. The mycotoxins that have been isolated and identified from Fusarium include Fusarium oxysporum, deoxynivalenol, 3-acetyl sphaerothecinol, 15-acetyl fulvicin, T- 2 toxins and zearalenone. Among them, Fusarium oxysporum and Deoxynivalenol have the highest content in moldy corn. The two kinds of toxins with high toxin content can be induced to produce esophageal, anterior stomach and glandular gastric hypertrophic changes in 20% proportion, suggesting that these two toxins have potential carcinogenic effects. It is further proved that Fusarium may be one of the main carcinogenic fungi in high-incidence areas. Alternaria alternata is also a fungus that has been studied in recent years. The contamination rate of Alternaria alternata in five high-incidence counties of Henan esophageal cancer (6.53%) was higher than that of three low-incidence counties (3.9%). The main mycotoxin contained in it is inter-associated with sporopolol monomethyl ether (AME) and alginol (AOH). The mutagenicity and tumorigenicity of Alternaria alternata are mainly related to these two toxins. The study found that AME and AOH have mutagenic effects on TA102 and E.Coli test bacteria, which can induce DNA single-strand breaks in USD and ZBS cells and rat hepatocytes of human amniotic membrane FL cells. AME can interfere with the transcriptional activity of rRNA, damage human lymphocyte DNA, induce V79 cell mutation, and transform NIH/3T3 cells. The transformed cells can grow on soft agar. The inoculated BALB/C nude mice have tumorigenicity. AME and AOH can promote lipid peroxidation and inhibit the activity of superoxide dismutase (SOD), which is associated with cell carcinogenesis. The cultured human embryonic esophageal epithelium was treated with AME or AOH in vitro for a short period of time, and DNA was extracted therefrom, and the DNA was transfected into NIH-3T3 cells, and the cells were malignantly transformed. Transformed cells can grow on soft agar and are tumorigenic. In recent years, it has also been demonstrated that A- or AOH-treated human embryonic esophageal epithelium has C-Ha-ras mutation and amplification, and activation and amplification of C-myc gene. AME and AOH induced human embryonic esophageal epithelial hyperplasia, which also successfully induced esophageal squamous cell carcinoma. The above results indicate that Alternaria alternata plays an important role in the etiology of human esophageal cancer. Some studies have shown that the micronucleus rate of red blood cells in mouse bone marrow induced by extract of Penicillium arcuticus is significantly different from that of the solvent control group (P<0.01), showing a significant dose-effect correlation. Mutagenesis experiments suggest that the metabolic extract of Penicillium arcuatus can directly damage genetic DNA. Bacillus subtilis DNA recombination test, UDs test, DSL test showed that Penicillium chrysogenum could produce mutagenic substances. The above results suggest that mold is one of the factors in the pathogenesis of esophageal cancer.
(2) The role of the virus: The role of the virus in the pathogenesis of esophageal cancer has also attracted the attention of scholars at home and abroad. The viruses currently studied are mainly human papillomavirus (HPV) and Epstein Barr Virous (EBV).
1HPV: The relationship between human papillomavirus infection and cervical cancer has been recognized. In recent years, studies have found that the esophagus is also a good site for HPV infection. HPV infection of esophagus is reported to be mainly type 6, type 16, and type 18. Currently, some studies suggest that HPV type 16 is associated with esophageal squamous cell carcinoma, and HPV type 18 is associated with adenocarcinoma. There are many studies on HPV16 in China. The detection of HPV16 DNA in esophageal cancer and adjacent tissues showed that the detection rates of HPV16 DNA in cancer and adjacent tissues were 60% and 51.95%, respectively. It is suggested that HPV16 infection is a common phenomenon of esophageal cancer, which may be related to the occurrence of esophageal cancer. HPV in vitro experiments have shown that it has a role in causing cell transformation, but the mechanism of action of HPV is still unclear. Some scholars believe that HPV DNA can be integrated into the DNA of esophageal cancer tissues, which may cause gene abnormalities to participate in tumor development. Some scholars believe that HPV may cause the occurrence of esophageal cancer by reducing local lymphocytes, destroying the local immune surveillance system, and synergistically with other carcinogenic factors. However, Lu Shixin and others failed to detect HPV DNA in esophageal cancer and adjacent tissues in Linxian County by means of molecular hybridization and polymerase chain reaction. It seems that the relationship between HPV and esophageal cancer needs further study.
2EB virus: relationship between EBV and cancer In the past, the literature mainly focused on nasopharyngeal carcinoma. Reports on the relationship with esophageal cancer are rare. Foreign Mori et al found that the positive rate of Epstein-Barr virus in esophageal cancer was 3.3%. Domestic Wu Mingyao found that the positive rate of esophageal cancer: EBVLMP-1 (potential membrane protein 1) was 6.3%. EBV-positive cells show morphological changes such as cytoplasmic loosening and vacuolar degeneration, which may be related to the response of EBV-infected cancer cells. Regarding the pathogenicity of EBV positive rate and EBV, there are generally two hypotheses: A.EBV infection occurs after canceration, and the EBV test of mucosal epithelial cells in this patient is often negative; B.EBV infection occurs before canceration, and It plays a role in the formation of cancer. Because of the low positive rate of cases found so far, the link between EBV and esophageal cancer remains to be further studied.
5. Genetic factors A large number of studies have shown that cancer is the result of long-term repeated effects of various environmental factors on individuals with different genetic qualities. The proportion of family history of cancer in patients with esophageal cancer has been significantly higher than that of the control group, suggesting that there is a genetic predisposition to esophageal cancer, and genetic factors may be an important risk factor for the onset. With the development of molecular biology and molecular genetics, there is a lot of evidence that the malignant transformation of normal cells involves changes in the structure and regulation of genetic material. What is inherited from the previous generation is not the tumor itself, but the susceptibility to cancer. . The nature of this tumor susceptibility may be caused by abnormal DNA structure or replication, transcription, and expression errors in the patient, or may be related to the activation or inactivation of carcinogens, the loss or loss of enzyme activity required for harmlessness, or may be congenital or acquired. Sex chromosome aberrations or the result of certain immune genetic defects. It has been observed that the chromosomal aberration rate of high-risk family members is significantly higher than that of the control group. Experiments have shown that lymphocytes of high-incidence family members are more susceptible to sister chromosome exchange (SCE), and possible endemic fragile sites have been found on their chromosomes, such as 1p13-p36 and 4q21-q31, which may be involved in esophageal cancer. Some important synergies. Studies have found that family susceptibility to esophageal cancer is associated with familial immunodeficiency, esophageal cancer patients with family history of cancer and their relatives, some immune functions are significantly lower than the control group without cancer family, and patients and their relatives have more Similar immunodeficiency defects. Whether this immune dysfunction is caused by genetic or environmental factors remains to be further studied.
6. Research on esophageal oncogene
(1) Oncogene: The DNA of esophageal cancer tissues and paracancerous epithelial tissues was studied, and it was found that most C-mye, EGFR gene amplification or expression enhancement. From esophageal specimens obtained from high-risk areas of esophageal cancer in China, Italy, and France, 32% of cases had cyclin D gene amplification, and 63% of cases had cyclin D mRNA overexpression. Other expression enhancements include Int-1, HER-1 genes, etc. The high expression and over-amplification of these oncogenes may be related to the occurrence of esophageal cancer.
(2) Tumor suppressor gene: There are abnormalities in the structure of Rb gene in about 1/3 of esophageal cancer and adjacent tissues, such as partial or partial loss of the fragment. About 10% to 70% of esophageal cancers have p53 gene mutations, and most of the mutations are in exons 5-9, and the detection rate of p53 gene loss is 43% to 52%. The loss rates of APC and MCC genes in esophageal cancer were 50% and 58%, respectively. The loss rate of adenocarcinoma appeared to be higher than that of squamous cell carcinoma, and the loss rate of DCC gene was 33%. The homozygous loss rate of p16 gene is 16.7%. The above suggests that the inactivation of tumor suppressor gene may also be an important link in the pathogenesis of esophageal cancer.
(3) Candidate tumor suppressor genes: Recently, Lu Shixin applied mRNA differential PCR display technology to identify four human esophageal cancer-related gene cDNA fragments, named ECRG1 to ECRG4, which were cloned and identified to confirm that ECRG1 and ECRG2 may be new esophagus. Cancer-associated candidate tumor suppressor genes, which may be involved in the development of esophageal cancer.
NMBzA and genetic abnormalities: Studying the relationship between environmental carcinogens and oncogene activation and tumor suppressor gene inactivation, NMBzA can lead to amplification or high expression of oncogenes C-myc, Int-2 and EGFR, and can lead to tumor suppressor genes. Mutation or deletion of Rb, APC and MCC. These suggest that the chemical carcinogen NMBzA can activate the proto-oncogene or inactivate the tumor suppressor gene during the initiation phase of carcinogenesis, which may be the cause of cancer rather than the result.
In recent years, the application of methylbenzylnitrosamine (MBNA) found in the environment of Linxian County to human fetal esophageal epithelium for 3 weeks, the epithelium was transplanted into the mesentery of BALB/C nude mice, and the MBNA of nude mice was continued. Results Squamous cell carcinoma occurred in the mesentery, no tumor in the esophagus, and no tumor in the control group. The DNA of the induced tumor is hybridized with the human specific repeat sequence, Alu sequence, and the Alu sequence is found in the induced tumor, which proves that the tumor originates from human tissues. The experiment confirmed for the first time that nitrosamine can induce human esophageal epithelial squamous cell carcinoma and provide direct evidence for the cause of nitrosamine in esophageal cancer in Lin County.
The above data suggest that the occurrence of esophageal cancer is the result of multiple factors, multiple stages and multiple oncogenes.
(two) pathogenesis
1. Tumor site distribution Clinically, the esophagus is usually divided into upper, middle and lower segments. From the entrance of the esophagus to the upper edge of the upper aortic arch, the lower segment from the lower edge of the lower pulmonary vein to the lower part of the portal. In 1987, the International Union Against Cancer (UICC) proposed a new segmentation criteria for esophageal cancer: the upper edge of the esophagus to the upper edge of the sternum is the cervical segment, and the lower part is the thoracic segment. The thoracic esophagus is divided into three sections: upper, middle and lower. From the upper edge of the sternal stem to the plane of the tracheal bifurcation, the upper part of the chest is the upper part of the tracheal bifurcation plane to the entrance of the iliac crest (the junction of the esophagus and the esophagus), and the lower part (including the anatomical ventral esophagus) (Fig. 1).
According to past statistics, although there are certain regional differences in the occurrence of esophageal cancer, reports in most countries are still relatively consistent. The most common sites for esophageal cancer are 50% of the middle and third segments; followed by the lower third. Segment, accounting for 30%; the upper 1/3 segment is less, about 20%. According to the Henan Linxian People's Hospital, the distribution of 633 cases of esophageal cancer was determined by the combination of esophageal cytology and X-ray. The upper, middle and lower segments were 11.7%, 63.4% and 24.9%, respectively.
2. Pathological type
(1) General type: Esophageal cancer can be divided into two categories: early and middle. Early esophageal cancer refers to carcinoma in situ (intraepithelial neoplasia) and early invasive carcinoma. The latter cancer tissue invades the submucosa but has not yet invaded the muscle layer.
1 early esophageal cancer: early patients with no obvious symptoms or mild symptoms, only in the high incidence of esophageal cancer by cytology screening can be found in early cases. Most of the lesions are confined to the surface of the mucosa, and no obvious mass is seen. Therefore, in the case of macroscopic classification, early and middle-stage esophageal cancer are different. Pathological features, the main lesions are confined to the superficial layer of the esophageal wall, except for a few papillary tumors, there are no obvious masses and manifested as mucosal lesions. Morphological studies of early esophageal cancer resection specimens in the past 20 years, generally early esophagus Cancer is divided into the following four types:
A. Concealed type: the esophageal mucosa of the lesion is flush with the surrounding normal esophageal mucosa. In the fresh specimen, the mucosa of the lesion is deeper than normal, pink, and the capillaries in the mucosa are dilated and congested, which is characterized by mild hyperemia or mucosal folds. Thick, under the microscope are cancer in situ. This type is the earliest manifestation of esophageal cancer and is easily missed in endoscopy.
B. erosion type: the esophageal mucosa of the lesion is slightly sunken or slightly erosive, the color of the erosion is deeper, the edge is irregular and map-like, and the boundary between the normal mucosa and the surrounding is clear. The erosion zone is fine-grained and occasionally has residual normal mucosal islands. Except for individual cases with fibrinous pseudomembrane covering, most of the erosion surface is relatively clean, and half of the tumors in situ and early invasive carcinomas are under the microscope.
C. Plaque type: The esophageal mucosa of the lesion is slightly swollen and bulging, the surface is rough and uneven, the color is gray, and it is pale, sometimes showing a small erosion area. The lesion boundary is clear, sometimes involving the esophagus for the entire week. The esophageal mucosal folds are thickened, disordered and interrupted, and the mucosal surface is rough, showing particles of varying thickness and psoriasis. This type of carcinoma in situ accounts for 1/3, and early invasive carcinoma accounts for 2/3.
D. Nipple type: The tumor has obvious nodular bulge, the esophageal mucosa of the lesion is papillary, or the umbilical shape protrudes into the esophageal lumen, and the diameter is 1~3cm. The boundary with the surrounding normal mucosa is clear, and the surface is generally smooth. There may be small erosions, sometimes covered with gray-yellow inflammatory secretions, occasionally smashed. Most of the microscopes are early invasive cancer.
Early lesions are generally small, but can affect the entire circumference of the mucosa, common with plaque and erosion, nipple type and concealed type are less common. Its distribution is the same as that of advanced esophageal cancer, with the middle section being more common and the lower section being second (Fig. 2).
2 middle and late stage esophageal cancer is roughly divided into: clinically advanced patients with esophageal cancer have clinical symptoms, a large number of pathological material analysis shows that the most medulla type, accounting for 56.7% ~ 58.5%; 蕈 umbrella type of 17% ~ 18.4%; ulcer The type is second, accounting for 11% to 13.2%; the narrowing type (8.5% to 9.5%) and the intraluminal type (2.9% to 5%) are less (Fig. 3, Fig. 4). The length of each type of tumor is different, most of the medulla is more than 5cm, while the majority of the umbilical, ulcer and constriction are below 5cm. The intraluminal type is sometimes large, the degree of dysphagia and various types of esophageal cancer. It is related to the extent of the esophageal circumference. Most of the narrowed and medullary types involve most or all of the esophageal circumference. Most of the umbrella type and ulcer type do not involve the entire circumference of the esophagus, and still retain the normal esophageal wall, so the food can still relax when swallowing, so the difficulty of swallowing is not heavy. The intracavitary type is more obvious because it occupies the lumen passage.
A. Medullary type: The tumor has invaded the whole layer of the esophageal wall, causing the wall to thicken significantly, involving most of the circumference of the esophagus or the whole week. The upper and lower edges of the cancer are sloping, and the surface often has different shades. Ulcer, the tumor has a gray cut surface, such as the brain. This type is more common, and the degree of malignancy is high;
B. 蕈 umbrella type: The tumor is oval in shape and protrudes into the esophageal lumen like a mushroom. The boundary between the bulging edge and the surrounding esophageal mucosa is clear. There are many shallow ulcers on the surface of the tumor, and the bottom is uneven, often covered with a layer of brown inflammatory exudate.
C. Ulcer type: The surface of the tumor has deep ulcers, and the shape is different. The ulcer generally penetrates into the muscular layer, and some even invade the fibrous tissue around the esophagus.
D. Constriction type: The tumor forms a distinct annular stenosis, involving the esophagus for the whole week. The boundary between the tumor and the normal tissue is unclear, the length is less than 5cm, the surface is erosive, and the proximal esophageal lumen is significantly expanded. There are also a small number of esophageal cancer specimens that protrude into the esophageal cavity like a polypoid. Therefore, some authors believe that this is another type of esophageal cancer, the intraluminal type.
(2) Histological type and classification: According to the histological features of esophageal cancer, it can be divided into four types: squamous cell carcinoma, adenocarcinoma, undifferentiated carcinoma, and carcinosarcoma.
1 Squamous cell carcinoma: originated in the esophageal mucosa, accounting for more than 90% of all esophageal cancer (Figure 5). Broder divides tumor cells into four grades based on their degree of differentiation.
Broder grade I: The tumor cells are well differentiated, the cells are polygonal, and there are many keratinization and intercellular bridges. This differentiated cancer cells account for more than 75%.
Broder II: Cancer cells are polygonal or round, with keratinized beads or scattered keratinization, medium cell differentiation, intercellular bridges, and mitotic figures. .
Broder III grade: cancer cells are poorly differentiated, but the characteristics of polygonal squamous cell carcinoma can still be seen. Even a little keratinized material can be seen, and the differentiated cancer cells can be seen in 25-50%.
Broder grade IV: The cancerous tissue is in a poorly differentiated state. There is no keratinization and intercellular bridge in the section, but the appearance of polygonal cancer cells can still be seen. It can be seen that differentiated cancer cells account for less than 25%.
The Broder four-level classification has the significance of judging prognosis. So far, domestic and foreign literatures are still applied in the classification of malignancy. However, the proportion of cancer cells with good differentiation and poor differentiation may be subjectively different. The degree of differentiation of cancer tissues may be different in different parts, so the percentage is not easy to calculate. In recent years, many scholars have classified squamous cell carcinoma into grades I, II and III according to the degree of differentiation of cancer cells. Grade I cancer cells often have obvious keratinization, insensitivity is not obvious, mitosis is rare; grade II cancer cells have less keratinization formation, more obvious atypia, mitosis is more common; grade III cancer cells are smaller and less cytoplasm The formation of keratinization is common, and nuclear division is common. This three-level classification method is more applicable and easier to grasp, but there are also large differences in statistics. Therefore, the criteria for determining histological grading are yet to be further studied.
2 adenocarcinoma: esophageal primary adenocarcinoma is relatively rare, can be divided into the following types:
A. Simple adenocarcinoma: The cancer cells are cuboidal or columnar, and the nucleus is round, oval or rod-shaped. The nuclear nucleus is parallel to the long diameter of the cell, and the nuclear chromatin is coarse. The cells can form an approximately circular gland. Cavity (Figure 6).
B. Adenosquamous carcinoma: including adenoid carcinoma and adenosquamous carcinoma. There are two components in the adenoma tissue, but the adenocarcinoma is obviously malignant. It shows that the cytoplasm is small, the nucleus is large, the nuclear abnormality is obvious, and the nuclear chromatin is coarse, forming a complete or irregular gland. kind. In adenocarcinoma tissues, there are well-differentiated squamous epithelial cells, which are rich in cytoplasm, small in nucleus, non-anamorphic, and even in the presence of intercellular bridges or keratinized substances. This kind of good squamous epithelium has obvious benign morphology, and the clinical prognosis is generally good. Therefore, most current authors call it adenosate carcinoma, or adenocarcinoma has squamous metaplasia. The histological images of adenosquamous carcinoma were mainly characterized by squamous epithelium and columnar epithelium, and both cells were heteromorphic. However, the adenocarcinoma has a distinct glandular structure, and the squamous epithelium also has a malignant morphology with a clear polygonal shape, sometimes with keratinization or intercellular bridges (Fig. 7).
C. Mucin epidermoid carcinoma: The tissue is derived from a glandular duct or acinar. The tumor tissue consists of two different types of cells, one is epidermal-like cells, the tumor cells are polygonal, cytoplasmic or squamous epithelial, or It is small, basal cell-like, with uniform cell size and shape, deep nuclear staining, and few mitotic figures. This epidermoid cell is mostly clustered; the other is differentiated high columnar epithelial cells with rich cytoplasm and transparency. The cell is large in size, the nucleus is round, small, and the size and shape are relatively uniform. The nucleus is located at the base of the high columnar cell, and the tumor tissue is composed of different sizes and irregular glandular cavities. The above two kinds of cells are mixed and the epidermal-like cells are generally found at the base of the columnar cells.
D. Adenoid cystic carcinoma: the tissue morphology should be consistent with mucoepidermoid carcinoma of the parotid gland, that is, there are glandular cavities of different sizes in different differentiated squamous cell carcinoma masses, which are covered with mucus secreting cells, and the secretion amount is not Etc. Sometimes a mucus paste is formed. Its organization is still inconclusive, some claim from the esophageal mucous glands, and some believe that the columnar epithelial carcinogenesis of embryonic remnants can simultaneously differentiate into squamous cells. The squamous cell components of mucoepidermoid carcinoma are common basal-like cells (so-called Intermediate cells) is also an evidence.
For the diagnosis of adenocarcinoma of the lower esophagus, we should be cautious. There are many cases of so-called esophageal adenocarcinoma, which is actually the invasion of the lower esophagus. Diagnosis of lower esophageal adenocarcinoma should meet the following criteria: 1 adenocarcinoma is the mucosal tissue or gland from the esophagus; 2 should determine the relative position of the junction of the cancerous tissue and the gastric epithelial squamous epithelium. If it can be judged that there is a certain distance above the junction, it is better; 3 if the cancer tissue is in situ in the esophagus, the differentiation must be confirmed by special staining.
3 undifferentiated carcinoma: in the undifferentiated carcinoma of the esophagus, mainly small cellesophagus caeinoma (SCEC), large cell undifferentiated carcinoma is extremely rare. Most of the undifferentiated carcinomas of esophageal small cells are oat cell carcinoma. This type of cancer cells is small, round, oval or even fusiform. It can be seen in typical oat-like cancer cells with very little cytoplasm. Naked nucleus, chromatin is dense and deeply stained, and the division is more common. Arranged into lumps of different sizes or diffuse growth, there may be a few fibrous interstitial spaces, and pseudo-adeno-like regions are also seen in cancer tissues. Silver staining, cancer cells are more positive, and neuroendocrine granules are visible by electron microscopy.
It is not uncommon to report that the incidence of SCEC is 0.05% to 5.5%. There was no significant difference in the age, sex, location and clinical symptoms of SCEC and esophageal squamous cell carcinoma. The pathological histomorphology and biological characteristics were significantly different, similar to pulmonary small cell carcinoma, and its main manifestations were: A. histological features, SCEC is also divided into oat cells, lymphoid cells, intermediate cells and mixed cell types. B. Histochemistry and immunohistochemistry, positive for silver staining. C. SCEC is highly invasive, with lymphatic and/or blood spreading early and high metastatic rate.
The origin of SCEC is still controversial. Most people think that it originates from Kulchisky cells or pluripotent primordial stem cells in the esophageal mucosa. This is because the esophageal and respiratory organs belong to the original foregut derivative. The carcinoid and small cell carcinoma of the trachea and lung are considered to be the source of the Coriolis cells, that is, the APUD cells. In addition, SCEC histochemistry and immunohistochemistry and ultrastructural studies have also demonstrated that a significant portion of them have APUD cell characteristics. In recent years, many scholars at home and abroad believe that gastrointestinal APUD cells are not derived from neural crest, but originated from endoderm, may be homologous to gastrointestinal glandular epithelium, that is, the source of pluripotent stem cells; they speculate that esophageal mucosal pluripotent primordial stem cells act as esophagus Pioneers of squamous cell carcinoma and lung cancer, as well as mucinous cell carcinoma (with neuroendocrine oat granules or non-oat reserve cells), which can also differentiate into the former.
4 Carcinosarcoma: less common, the tumor is mainly sarcoma components, often fibrosarcoma, rare leiomyosarcoma, rhabdomyosarcoma, chondrosarcoma and undifferentiated sarcoma. The cancer tissue has fewer components, and is mostly confined to the mucosa and submucosa of the base of the tumor pedicle, and a few can infiltrate the muscle layer.
3. The histogenesis of esophageal cancer The underlying lesions of esophageal mucosa include chronic esophagitis, esophageal epithelial hyperplasia and heterosexual hyperplasia. From a large number of research work, the incidence of chronic esophagitis is high among residents with high incidence of esophageal cancer, and the esophageal epithelial dysplasia caused by some reasons is also high. This is the esophagus of residents with high incidence of esophageal cancer. The basis for high cancer incidence. General hyperplasia of the esophageal epithelium is the basis of canceration and generally does not act as a precancerous lesion. The esophageal epithelial dysplasia is a precancerous lesion. According to the cytological follow-up observation of severe dysplasia, the cancer rate of severe dysplasia for 5-8 years is 15%-20%.
From morphology and cell biology, it can be seen that the proliferation and dysplasia of the esophageal epithelium begins with basal cells. As the lesion progresses, the epithelial cells of the basal and parabasal layers show hyperplasia or dysplasia, enlarged nuclei, thickened nuclear chromatin, prominent nucleoli, and increased division. Along with the sequence of epithelial hyperplasia, dysplasia, carcinoma in situ, and invasive carcinoma, the biological characteristics of epithelial cells also undergo a series of changes. The DNA content of the microscopic spectrophotometer was found to be diploid or nearly diploid in the normal esophageal mucosa epithelium, while the dysplasia DNA distribution was dominated by proliferative ploidy, and a considerable part of aneuploidy appeared. DNA The synthesis is significantly increased.
It is generally believed that the occurrence of esophageal cancer is a series of evolution from hyperplasia to dysplasia to carcinogenesis, and it is also a process from quantitative change to qualitative change. On the basis of the basic background of the esophagus (such as inflammation, hyperplasia, dysplasia, etc.), a series of proliferative changes occur in the epithelium. On this basis, the mutation of epithelial cells caused by certain factors, from benign proliferation to malignant proliferation, eventually develops into irreversible esophageal cancer. It is generally believed that the occurrence of esophageal cancer may follow the following pattern (Figure 8):
Many esophageal diseases are considered to be precancerous lesions of esophageal cancer, such as chronic esophagitis, Barrett's esophagus, ulcerative esophagitis, esophageal stenosis, leukoplakia, Hummer-Vinson syndrome, giant esophagus, esophageal achalasia, etc., but The incidence of these lesions in patients with esophageal cancer in China is not high, and they may not be the main cause of esophageal cancer in China.
4. There are ways to spread and metastasize the spread and metastasis of esophageal cancer
(1) Diffusion in the esophageal wall: The esophageal mucosa and submucosa are rich in longitudinal lymphatic vessels, and cancer cells can spread up and down along the lymphatic vessels. The microscopic spread of the tumor is larger than that seen by the naked eye, because the cut esophageal specimens are much shorter, especially after the formaldehyde is fixed, and the true diffusion degree is not easy to be sure, but the distance of the upward diffusion is considered to be much larger than the downward direction. The literature reports that the positive margin of the tumor is associated with anastomotic recurrence. It is not uncommon for people to spread upwards beyond the tumor margin by 5 to 6 cm, even up to 10 cm, but the downward diffusion is generally not more than 5 cm. Sometimes the spread of cancer cells along the esophageal mucosa is not continuous and leaping, so it is important to remove enough length from the surgery.
(2) Direct infiltration: This is a further development of esophageal wall infiltration. Cancer cells spread outward from the mucosa, reaching the esophagus and invading adjacent organs. The organs involved are different depending on the lesion. Upper esophageal cancer can invade the throat, trachea, thyroid and soft tissue of the neck. Middle esophageal cancer is mainly caused by invasion of the trachea, bronchus, lung, mediastinum and aorta. The lower esophageal cancer invades the abdominal organs such as the mediastinum, cardia, pericardium and stomach. Esophageal cancer invaded the mediastinum by 20%, and the middle and lower esophageal cancer invaded the mediastinum, the former was 19.5%, the latter 20.6%. Therefore, there is often a wide range of mediastinal inflammation, causing pneumonia and lung abscess formation. When the aorta is invaded, it can cause aortic rupture and massive bleeding.
(3) Lymphatic metastasis: The lymphatic metastasis pathway of esophageal cancer is basically consistent with normal lymphatic drainage. Because the lymphatic drainage of the esophagus is mainly in the longitudinal direction, the longitudinal lymphatic vessels are six times as large as the transverse lymphatic vessels, so the lymph node metastasis is mainly regional and up-and-down bidirectional metastasis. First, the main esophageal lymph nodes in the tumor site, followed by the cervical deep lymph nodes and supraclavicular lymph nodes. Most of the upper thoracic segment is along the esophagus to the cervical lymph nodes; the middle thoracic segment is from the upper to the upper thoracic esophageal, paratracheal lymph nodes, even to the lymph nodes of the neck, but also down to the cardia, the left gastric artery Dry metastasis of lymph nodes, the above behaviors; the lower thoracic segment is also the two-way transfer of the upper and lower; but the following line of transfer is more. The area of lymphatic metastasis is affected by many factors. Posllethwait combines 9 autopsy materials with lymph node metastasis.
Generally, the larger the tumor (long), the deeper the infiltration, and the lower the degree of differentiation, the more likely the lymph node metastasis will occur. The shallower the lesion is infiltrated, the less chance of a continuous metastasis, but the more chances of a leaping metastasis. Because the deep and submucosal layers of the esophageal mucosa have a rich network of lymphatic vessels arranged along the longitudinal axis of the esophagus, they communicate with each other. The submucosal lymphatic network traverses the longitudinal lymphatic vessels of the esophageal muscle layer and the extramuscular fibrous membrane through the collaterals, and the lymphatic vessels are injected into the esophageal lymph nodes along the esophageal wall. In the early stage, cancer cells invade into the lymphatic vessels deep into the mucosa of the esophagus, flow up and down, leave the local main lesions, and directly transfer to the distant lymph nodes with lymphatic flow, which constitutes a metastatic lymph node metastasis. When the cancer infiltrates into the esophageal adventitia, the tumor not only infiltrates the superficial mucosa deep and submucosal lymphatic vessels, but also directly infiltrates into the deep lymphatic vessels of the muscular outer membrane, so with the distant metastasis, the continuous metastasis increased. If the cancer cells or tumor thrombus invading the lymphatics leave the main lesion with the lymphatic flow, stay or embolize in a certain lymphatic vessel, forming a new cancerous foci, which forms a jumping metastasis in the esophageal wall.
(4) Hematogenous metastasis: relatively rare, mainly seen in advanced cases, the most common transfer to the liver, lung, skeletal system, and a few transferred to the kidney, adrenal gland, peritoneum, heart and brain. Domans reported 824 cases of esophageal cancer, according to the incidence of metastasis in the tumor site.
5. Pathological Staging In 1987, the International Union Against Cancer (UICC) proposed the TNM staging method for esophageal cancer.
In the table, Tis is carcinoma in situ, T1 cancer invades the submucosa, T2 cancer invades the muscle layer, T3 cancer penetrates the muscle layer and reaches the fibrous membrane, and T4 cancer invades adjacent organs.
N0 has no regional lymph node metastasis, requiring test specimens containing at least 6 lymph nodes, N1 with regional lymph node metastasis (cervical esophageal cancer including neck and supraclavicular lymph nodes; intrathoracic esophageal cancer including mediastinal lymph nodes and periplasmic lymph nodes, but excluding celiac artery Para-lymph node).
M0 has no distant metastasis, and M1 has distant metastases [including distant lymph nodes (or other organs)]. In 1997, the new version divides M1 into M 1a and M1b. In the lower thoracic carcinoma, the lymph node metastasis of the celiac artery is M 1a, and the other distant metastasis is M1b. The cervical lymph node metastasis is M 1a, and the other distant metastasis is M1b. There is no M 1a in the middle thoracic carcinoma, and non-regional lymph node metastasis or other distant metastasis is M1b.
symptom:
Early esophageal cancer is confined to the mucosal or submucosal layer of the esophagus, and there are no specific clinical symptoms or symptoms at the onset of the disease. Some patients may have some insidious or non-specific symptoms, such as post-sternal discomfort, indigestion or transient swallowing, or due to local esophageal spasm caused by the tumor, the patient may be regular or periodic. Esophageal obstruction symptoms.
1. Early esophageal cancer early esophageal cancer is not obvious, and multiple interruptions occur, easily overlooked. According to Huang Guojun and Wu Yingwei (1984), a retrospective analysis of early esophageal cancer patients found in the esophageal cytology census in high-risk areas of esophageal cancer in Henan Province, China. The main clinical symptoms of these patients are post-sternal discomfort or pain, or conscious. There is a sense of friction, and some patients have a "heartburn" sensation, acupuncture-like or traction-like pain in the upper abdomen, especially when eating rough, overheated or irritating food. Or when eating, I feel that the swallowing process becomes slower. Mostly due to local lesions to stimulate abnormal or esophageal motility, or due to local inflammation, erosion, superficial ulcer, tumor infiltration, often repeated, intermittent period can be asymptomatic, can last for several years. Other rare symptoms include swelling of the sternum and dryness of the throat. About 3% to 8% of cases can be without any feeling. About 90% of patients with early esophageal cancer have the above symptoms. According to Bains and Shields (2001), the only symptom of patients with early-stage esophageal cancer diagnosed is pain when swallowing food, but the vast majority of patients do not pay attention to it until they have progressive dysphagia. In order to detect esophageal cancer early, you must be familiar with the early symptoms of esophageal cancer, and take the appropriate auxiliary examination without any opportunity to further confirm the diagnosis.
(1) Foreign body sensation in the esophagus: The location of foreign body sensation is consistent with esophageal lesions. As the disease progresses, symptoms such as swallowing food sensation and even pain are successively present. The cause of this symptom may be due to mucosal congestion and swelling of the esophageal lesion, resulting in a decrease in the stimulation threshold of the submucosal plexus of the esophagus.
(2) Slow and stagnant food: After swallowing food, the food is slow and has a feeling of stagnation. The upper part of the esophagus and the middle part of the site are often shallow, gradually aggravated, and accompanied by other symptoms. The mechanism may be mainly due to functional changes, or may be due to a wide range of "cancer" in esophageal cancer, and chronic inflammation of the esophageal mucosa with varying degrees.
(3) Post-sternal pain, bloating discomfort or swallowing pain: the nature of the pain may be a burning, acupuncture or traction friction. In the initial stage, the symptoms are mild and only intermittent, and each duration may be short, and medication may be relieved. In the future, the symptoms will worsen, recurrent, and prolonged duration.
(4) Dryness and tightness of the pharynx: An abnormal feeling may occur due to the contraction of the esophageal sphincter caused by the esophageal lesion.
(5) Pain under the xiphoid or upper abdomen: manifested as persistent sorrow or burning tingling, which occurs when swallowing food, weakens or disappears after eating, and is inconsistent with the lesion. It may be caused by the incoordination of the esophageal motor function caused by the lesion, and the strong sacral contraction of the cardia sphincter.
2. Middle and late stage esophageal cancer is more typical in advanced esophageal cancer, and it is not difficult to diagnose. When the tumor involves the full layer of the esophageal wall and invades the tissue structure or organs around the esophagus, the patient has a series of corresponding advanced symptoms and signs related to it, suggesting that esophageal cancer has progressed to a stage that is difficult to cure. Its clinical symptoms and signs are mainly:
(1) difficulty in swallowing: dysphagia is the main symptom of advanced esophageal cancer, and is the most common complaint. About 90% of patients have this symptom, which is the most prominent symptom of esophageal cancer. The esophagus is a muscular tubular organ with an expanding function. Only after the tumor invades the local esophageal inner diameter or the circumference of the circumference, the patient has symptoms of esophageal obstruction, that is, difficulty in swallowing. Because the esophageal wall has good elasticity and expansion ability, the symptoms of dysphagia are not significant when the cancer does not involve more than half of the esophagus. The degree of difficulty in swallowing is related to the type of pathology, and the narrowed and medullary forms are more severe than others. About 10% of the cases of symptoms or initial symptoms are not about 20% to 40% of people with difficulty in swallowing, and cause delay in the diagnosis of esophageal cancer. Many patients consciously change their original eating habits when they are swallowed. When they eat meat or hard food, they carefully chew them and then swallow them. Sometimes they drink the water or drink the soup and then swallow the food. Into the stomach, some patients change to a liquid or semi-liquid diet. When a patient is seen for difficulty swallowing, the symptoms often last for about 6-8 months, and some are longer. Difficulty in swallowing is a mechanical obstruction of the esophageal tumor, or a neuromuscular lesion and dysfunction that governs swallowing.
More than 80% of patients with esophageal cancer have a major clinical manifestation of dysphagia. Dysphagia sometimes manifests as a slight discomfort after the sternum during eating, often transient, and does not occur for weeks or months thereafter; some patients present with swallowing pain or even complete obstruction of the esophageal lumen. The typical clinical symptoms are progressive dysphagia, indicating that the tumor is obstructing the esophageal lumen; this typical symptom occurs when the tumor invades more than 2/3 of the local esophageal wall circumference causing esophageal stenosis, but there are exceptions. At first, the difficulty in swallowing was intermittent, but it quickly turned into persistence. At the beginning, the patient felt difficulty swallowing when eating solid food, and then eating soft food also had difficulty swallowing. Finally, eating liquid food felt difficulty in swallowing. Patients with severe obstruction of the esophagus sometimes have difficulty drinking water.
According to Wu Yingwei and Huang Guojun (1974), the severity and development of dysphagia in patients with advanced esophageal cancer are related to the gross pathological type and other local changes of the tumor: the narrowing type of swallowing difficulty is the most obvious and persistent; the ulcer type may not appear. Obvious difficulty in swallowing; medullary, paralyzed or intraluminal has more difficulty in swallowing. Sometimes due to necrosis of cancerous tissue, symptoms of difficulty in swallowing may be temporarily relieved.
1 The symptoms of dysphagia in patients with constrictive esophageal cancer are most obvious and typical.
2 Patients with ulcerated esophageal cancer have no significant dysphagia. Even if the disease progresses from advanced stage to advanced stage, the patient does not necessarily have significant difficulty in swallowing.
3 蕈 Umbilical esophageal cancer Before the tumor completely blocked the esophageal lumen or blocked most of the esophageal cavity, the symptoms of eating difficulties were not obvious.
4 Most patients with medullary esophageal cancer have severe symptoms of difficulty in eating hypopharynx. Sometimes, due to the ischemic necrosis of the cancer tissue, the tumor is reduced, and the symptoms of difficulty in swallowing can be temporarily relieved, but the symptoms relapse soon.
5 The esophageal mucosa of the esophageal cancer has aggravation of edema and inflammation, and the symptoms of dysphagia are aggravated. The symptoms of dysphagia are alleviated when the reduction or regression occurs.
(2) Pain: Some patients have swallow pain, pain behind the sternum or between the shoulders when swallowing food. According to the tumor site, it has been caused by external invasion caused by inflammation around the esophagus, mediastinal inflammation or deep ulcer of the esophagus. Pain caused by a lower thoracic tumor can occur under the xiphoid or upper abdomen. If there is persistent chest pain, it is mostly caused by cancer invasion and/or compression of the pleura and spinal nerves. Esophageal cancer itself and inflammation can reflexively cause increased secretion of esophageal glands and salivary glands, and can cause cough and pneumonia through transesophageal motility. Unlike the pain that occurs in early cancer, it is more severe and persistent. The nature is dull, burning or stinging, which is aggravated by each diet. The site of pain is often consistent with the lesion, and occurs mostly in ulcerated patients.
Sustained chest and back pain is caused by tumor invasion of the paravertebral fascia and aorta. Tumors cause esophageal fistula above the obstruction site after esophageal obstruction, or cancerous ulcers formed by esophageal cancer, and local esophageal dilatation when the food passes through the cancer site, and contraction of the muscular layer of the esophageal wall. The patient has chest pain or one. Excessive chest and back pain, some patients complain of transient post-sternal pain, and the pain can be released to the back or neck. This pain symptom is more clinically significant than persistent post-sternal discomfort or upper abdominal pain, and it is often reflected that the invasion of the cancer in the esophageal wall has reached a considerable degree. Once the tumor invades the intercostal nerves and retroperitoneal nerves, the patient's chest and back pain tends to be persistent and severely painful, sometimes unbearable, affecting the patient's rest and sleep.
Cases with initial symptoms of pain account for about 10% of the total number of patients with esophageal cancer. Careful analysis of the location and nature of the pain, combined with imaging data on esophageal cancer, has the significance of diagnosis and prognosis.
(3) hoarseness: When the cancer tissue invades or oppresses the recurrent laryngeal nerve, vocal cord paralysis occurs, and the patient has hoarseness or even a loss of voice. It is more common in the upper esophageal cancer involving the left recurrent laryngeal nerve, and sometimes the enlarged metastatic lymph node is compressed. Recurrent nerves, the patient has hoarseness symptoms, often suffer from aspiration due to aspiration, sometimes causing aspiration pneumonia. Laryngoscopy showed that the vocal cord on the affected side could not be abducted and was in the middle position, indicating that the vocal cords were paralyzed. The generally affected vocal cords were the left vocal cords, and occasionally the right side.
(4) Hiccup: It is often the manifestation of esophageal cancer itself, metastatic mediastinal lymph node invasion (oppression) of the phrenic nerve and paralysis of the diaphragm and its motor dysfunction.
(5) Vomiting: It often occurs when the difficulty of swallowing is aggravated. Whenever it starts, it will spit. Whenever it is eaten, it will spit. If it is serious, it will not vomit. Most of the vomit is something that cannot be passed through the lower pharynx, mainly mucus and food that is trapped above the narrowed part of the esophagus.
(6) Respiratory symptoms: aspiration and direct invasion of the trachea and bronchus, the patient will have cough, dyspnea and pleurisy-like chest pain. High-grade esophageal cancer can cause coughing and difficulty breathing when the fluid is swallowed, because the esophageal lesion causes the fluid to flow back into the trachea. In addition, due to cancer tissue invasion, if the tumor penetrates the trachea and bronchus, mediastinum or mediastinal large blood vessels, the patient will have tracheal-esophageal fistula, acute mediastinal inflammation or even fatal bleeding. At the level of tracheal carina, the leading edge of the left main bronchus is adjacent to the middle part of the esophagus. If the middle esophageal cancer penetrates the left main bronchus, causing esophageal-tracheal, esophageal-bronchial spasm and aspiration pneumonia, characteristic swallowing may occur. cough. Severe cases can be complicated by pneumonia and lung abscess, and some patients have hemoptysis.
(7) Weight loss: Weight loss is the second common symptom in patients with esophageal cancer. According to the analysis of cases of large esophageal cancer (1000 cases or more), about 40% of patients have weight loss, mainly due to dysphagia, vomiting and pain. Related, it is also related to the consumption caused by the tumor itself. If the patient has obvious weight loss and systemic malnutrition, it is more likely that the tumor has reached the advanced stage, which is also one of the clinical manifestations of cachexia.
According to Galandiuk et al (1986), Launois et al (1983) and Isolauri et al (1987) analysis of clinical data of patients with treated esophageal and cardiac cancer, the main clinical symptoms and incidence of the patient are as follows: 1 difficulty in hypopharyngeal: 85.4 %; 2 weight loss: 60.9%; 3 pain: 26.5%; 4 nausea: 22.8%; 5 hoarseness: 4.4%; 6 cough: 2.5%. Among them, the following dysphagia, weight loss and pain are the most common. In clinical practice, patients who have difficulty complaining of difficulty in swallowing must be alert to the possibility of having esophageal cancer. At the same time, they should choose simple, easy and reliable diagnostic methods to make a diagnosis. With the development of modern clinical medicine, there are many diagnostic methods for esophageal cancer, but the commonly used diagnostic methods in the clinic are chest X-ray film examination, esophageal X-ray barium meal examination, endoscopy and esophageal CT scan.
The early diagnosis of esophageal cancer is very important, but at this time, there is often a lack of clear diagnosis basis. Therefore, a variety of factors should be combined to seek early diagnosis and early treatment of suspicious cases. Clinical manifestations combined with X-ray barium meal angiography, exfoliative cytology, endoscopy, chest CT scan, esophageal endoscopic ultrasonography are easier to diagnose. Clinical practice should be carried out in a simple and orderly manner. The first three tests are indispensable, especially endoscopy, which is superior to X-ray examination in positioning, length, second cancer, and benign stenosis. Sex. For suspected cases, esophageal barium meal imaging or double contrast angiography should be performed. For patients with clinical symptoms or suspicions who cannot be diagnosed, fiberoptic esophagoscopy should be performed early. Clipping multiple pieces of living tissue under direct vision for histopathological examination can help diagnose.
CT scan, EUS, etc. can determine the level of invasion of esophageal cancer, the depth of outward expansion and the presence or absence of mediastinum, lymph nodes or intra-abdominal organ metastasis, which can greatly improve the possibility of surgical surgery.
Clinical stage of the tumor:
The staging of esophageal cancer commonly used in China, according to clinical symptoms, X-ray findings, surgical findings and postoperative pathological examination, was established at the National Esophageal Cancer Work Conference in 1976. If there is no surgical specimen, it can be staging according to the X-ray. The length of the lesion seen on the X-ray is generally longer than that seen in the surgery.
diagnosis:
The disease should be identified with the following diseases: The following diseases should be differentiated from esophageal cancer, and cancer should not be excluded. If the various tests cannot be determined, they can be followed up, at least once a month.
1. Patients with esophageal varices often have other signs of portal hypertension. X-ray examination showed thickening of the mucosal folds in the lower esophagus, distortion, or a bead-like filling defect. Severe varicose veins under the fluoroscopy showed that the esophageal peristalsis was weakened and the expectorant passed slowly. However, the wall of the tube is still soft, and the elasticity is also present. There is no local stenosis or obstruction, and esophagoscopy can be further identified.
2. 贲 痉挛 痉挛 also known as achalasia, due to vagus nerve and esophageal wall plexus degeneration, or excessive sensitivity to gastrin, causing esophageal peristalsis and lower esophageal sphincter relaxation, so that food can not pass through the cardia, The general course of disease is longer, the patient is more common in young women, the symptoms are light and heavy, and the difficulty of swallowing is mostly intermittent, often accompanied by post-sternal pain and reflux. The use of antispasmodic drugs can often relieve symptoms, reflux It usually contains no bloody mucus. Generally there is no progressive weight loss (but in the late stage of achalasia, when the obstruction is severe, the patient may have weight loss). X-ray examination of the lower end of the esophagus was smooth beak-like or funnel-shaped stenosis, smooth edges, inhalation of isoamyl nitrite and the cardia gradually dilated, allowing the tincture to pass smoothly. Endoscopic biopsy without evidence of cancer can be identified.
3. Esophageal tuberculosis is relatively rare, generally secondary, such as proliferative lesions or tuberculoma, can lead to varying degrees of obstruction, difficulty swallowing or pain. The progress of the disease is slow, and there are more young and middle-aged patients, and the average age of onset is less than that of esophageal cancer. There is often a history of tuberculosis, OT test is positive, there are symptoms of tuberculosis, endoscopic biopsy helps identify. There are three manifestations of esophageal angiography: 1 filling defect and ulcer in the esophagus, the lumen of the lesion is slightly narrow, the wall of the tube is slightly stiff, the shadow is large and obvious, the edge of the shadow is not complete, and the surrounding filling defect is not obvious. 2 The side wall of the esophagus is filled with defects, and the mass formed by the mediastinal lymph node tuberculosis around the esophagus oppresses the esophageal cavity and invades the esophageal wall. 3 esophageal fistula formation. It is characterized by a small protruding shadow of the esophageal wall, like a small shadow, with no filling defects around it. For mediastinal lymph node tuberculosis, complicated with lymph node esophageal fistula. Finally, the diagnosis is determined by esophageal cytology or esophagoscopy.
4. Esophagitis esophageal hiatus hernia complicated with reflux esophagitis, similar to early stinging or burning pain of esophageal cancer, X-ray examination of mucosal texture rough, mild esophageal stenosis, sputum retention, some cases Mucosal shadows can be seen. For cases that are not easily confirmed, esophageal cytology or esophagoscopy should be performed.
Iron deficiency pseudo esophagitis This disease is more common in women, in addition to difficulty in swallowing, there are small cell hypochromic anemia, glossitis, gastric acid deficiency and anti-A. After iron treatment, the symptoms improved quickly.
5. The esophageal diverticulum can occur in any part of the esophagus. The more common is the traction diverticulum. It is mostly asymptomatic at the beginning. It can show different levels of dysphagia and reflux afterwards. When drinking water, it can smell "squeaky" and have chest tightness or Symptoms such as burning pain after heartburn, heartburn or foreign body sensation after eating. Due to the long-term accumulation of food in the sputum room, there may be obvious bad breath. Sometimes, due to changes in body position or nighttime sleep, diverticulum fluid may cause aspiration and cough. X-ray multi-axis fluoroscopy or pneumatic double contrast check can show the diverticulum.
6. The benign esophageal stricture has a history of acid and alkali chemical burns. X-ray shows esophageal stricture, mucosal wrinkles disappear, the wall is stiff, and the stenosis gradually transitions to the normal esophageal segment. Clinically, be wary of the possibility of cancer on the basis of long-term inflammation.
7. Benign esophageal tumors generally have a long course of disease, slow progress, and mild symptoms. Most of them are esophageal leiomyoma. In typical cases, the symptoms of dysphagia are mild and the progress is slow. X-ray and esophagoscopy show a swelling of the surface mucosa. The round or "ginger" wall is in the filling defect, and the surface mucosa is flattened. "Smear", but no ulcers. The local lumen is dilated normally, and the endoscope can see a circular mass that rises under the normal mucosa, and the phenomenon of "sliding" under the mucosa can be seen in the peristalsis of the esophagus. Sometimes it is not easy to distinguish from a small amount of esophageal cancer that grows on the side wall and mainly spreads under the mucosa, but the latter does not see "sliding" under endoscopy.
8. Esophageal leiomyosarcoma generally has two forms, one is polyp type and the other is infiltrating type. Polypoid type can be seen in the esophageal cavity nodular or polypoid mass, the tumor perimeter is clear, uplift, valgus. There is an ulcer in the center, the ulcer surface is uneven, and the mass protrudes out of the cavity. X-ray showed that the polyp type was obviously dilated in the esophageal lumen. When there was a huge mass in the cavity, there were many polypoid filling defects of different sizes. There were shadows in the mucosal destruction, the turbulence was not smooth, and the lumen was displaced. Common soft tissue masses outside the lumen, much like mediastinal tumors, but can be seen in esophageal angiography and the esophageal wall is clearly diagnosed. Infiltrating X-ray findings are similar to esophageal cancer.
9. Changes in esophageal pressure refers to oppression and dysphagia caused by abnormalities in the organs adjacent to the esophagus. Some diseases such as lung cancer mediastinal lymph node metastasis, mediastinal tumor, mediastinal lymph node inflammation, etc. can cause partial or severe stenosis of the esophagus, resulting in severe dysphagia symptoms, sometimes misdiagnosed as esophageal cancer. Esophageal barium meal imaging can often rule out the disease of the esophagus itself.
10. Ryukyu This disease is a functional disease. The onset is related to mental factors and is more common in young women. Patients often have a pharyngeal foreign body sensation that can disappear when eating, often induced by mental factors. There is no organic esophageal lesion in this disease, and endoscopy can be differentiated from esophageal cancer.
11. Iron-deficient pseudomembranous esophagitis is mostly female. In addition to difficulty in swallowing, there may be small cell hypochromic anemia, glossitis, gastric acid deficiency and anti-A.
12. Lesions around the esophagus such as mediastinal tumor, aortic aneurysm, goiter, and enlarged heart. In addition to the mediastinal tumor invading the esophagus, X-ray barium meal examination showed a smooth compression of the esophagus and normal mucosal lines.
complication:
Complications of esophageal cancer are more common in advanced patients.
1. In advanced cases of cachexia, due to the difficulty of swallowing, the long-term hunger leads to negative nitrogen balance and weight loss, which has a direct impact on the incidence of complications and operative mortality after resection of esophageal cancer. In fact, every patient with advanced esophageal cancer with obstructive symptoms has different degrees of dehydration and total body fluid loss due to difficulty in oral feeding. The patient developed cachexia and marked loss of water, which was characterized by high weight loss, weakness, dry skin and dryness, and was in a state of exhaustion.
2. Hemorrhage or hematemesis Some patients with esophageal cancer have vomiting. Individual esophageal cancer patients have hematemesis due to tumor invasion of large blood vessels, and occasionally hemorrhage. According to Wu Yingwei and Huang Guojun (1974), 24 (2.8%) of a group of 841 patients with esophageal and cardiac cancer had hematemesis, blood from esophageal cancer, cancerous lungs or large blood vessels in the chest. Hematemesis is generally a clinical symptom of patients with advanced esophageal cancer.
3. Organ transfer If there are important organs such as lung, liver, brain, etc., there may be peculiar symptoms of dyspnea, jaundice, ascites, coma and other organs. Esophageal cancer patients with esophageal-tracheal fistula, supraclavicular lymph node metastasis and other organ metastasis, recurrent laryngeal nerve palsy and cachexia are all advanced esophageal cancer.
4. Sympathetic ganglion compression sympathetic ganglia, resulting in sympathetic paralysis (Homer syndrome).
5. Water and electrolyte disorders Due to difficulty in swallowing, such patients have a tendency to develop severe hypokalemia and muscle weakness. Normal people secrete about 1 to 2 liters of saliva per day, and the inorganic substances include sodium, potassium, calcium and chlorine. The concentration of potassium in saliva is higher than the concentration of potassium in any other gastrointestinal secretions, typically 20 mmol/ml. Therefore, patients with esophageal cancer may have significant hypokalemia when they are unable to swallow saliva due to difficulty in swallowing.
Some squamous cell carcinomas can produce parathyroid hormone and cause hypercalcemia, even if the patient can have hypercalcemia without bone metastasis. Patients with esophageal cancer without bone metastases before surgery have hypercalcemia, which is often a sign indicating poor prognosis.
6. Aspiration pneumonia due to aspiration caused by esophageal obstruction and aspiration pneumonia, patients may have symptoms of fever and systemic poisoning.
7. Caused by cancer metastasis, such as cancer cells invading the recurrent laryngeal nerve causing vocal cord paralysis and hoarseness; tumor oppression and invasion of trachea, bronchial irritability and irritating dry cough; invading the phrenic nerve, causing diaphragmatic paralysis; invading the vagus nerve, making heart rate Accelerate; invade the brachial plexus, cause acidosis, pain, paresthesia; oppression of the superior vena cava, causing superior vena cava compression syndrome; liver, lung, brain and other important organ cancer metastasis, can cause jaundice, ascites, liver failure Complications such as difficulty breathing, coma, etc.
8. Esophageal perforation: Advanced esophageal cancer, especially ulcerated esophageal cancer, caused by localized erosion and severe ulceration of the tumor. Different symptoms appear due to different perforation sites and adjacent organs. Wearing a snorkel caused by esophageal tracheal fistula, sputum anatomy when entering the diet, especially in the intake of fluid diet symptoms; penetrating into the mediastinum can cause vertical sputum inflammation, chest tightness, chest pain, cough, fever, increased heart rate and white blood cells, etc. Penetration into the lungs causes lung abscess, high fever, cough, sputum purulent sputum, etc.; through the aorta, causing esophageal aorta spasm, can cause massive bleeding and lead to death.
9. According to other reports, some esophageal squamous cell carcinomas have hypertrophic osteoarthrosis, some patients with occult esophageal cancer have dermatomyositis, and some patients with obstruction of the esophagus have "swallowing syncope". (swallow syncope), may be a vagus-medium response.
treatment:
(a) treatment
Treatment for esophageal cancer includes surgical treatment, radiation and medical treatment, and surgery plus radiation or drug combination therapy. The most important measures to improve the treatment of esophageal cancer are early diagnosis and early treatment. The choice of treatment plan for esophageal cancer depends on the history, the location of the lesion, the extent of tumor expansion and the general condition of the patient.
1. Surgical treatment China has been conducting esophageal cancer surgery for more than 40 years. Since the founding of New China, the surgical treatment of esophageal cancer has been greatly popularized and improved. At present, the resection rate of general advanced esophageal cancer is about 80% to 85%, and the operative mortality rate is below 5%.
(1) Indications and contraindications:
1 surgical indications: esophageal cancer diagnosis has been established, the extent of lesions is limited (5 ~ 6cm), no distant metastasis, no surgical contraindications should first consider surgery. include:
A. T3N1M0 in stages 0, I, IIa, IIb and III of the UICC stage.
B. Radiation therapy for uncontrolled lesions or recurrence cases, there are no signs of local obvious invasion or distant metastasis.
C. The age is generally no more than 70 years old, and a few elderly are close to 80 years old, but cases with younger physiological age can also be carefully considered.
D. Known lesion length is not closely related to treatment prognosis, so it is only a reference indicator when selecting patients.
2 surgical contraindications are:
A. AIDS constitution.
B. Phase III late (T4 any NM0) and IV in the ICC staging.
C. Other systemic functions of the body are obviously obstructive and cannot tolerate surgery and anesthesia. Important organs have serious comorbidities, such as low lung function, heart disease with heart failure, or myocardial infarction within half a year.
(2) Judgment of the possibility of resection: For each case of surgery, the surgeon should judge the possibility of resection before surgery. The judgment basis is:
1 lesions: the upper segment resection rate is the lowest, from 66.7% to 89.5%; the middle segment is followed by 79.1% to 94.5%; the lower segment is the highest, reaching 87.2% to 98.4%.
2 The esophageal direction of the diseased segment: If it is inconsistent with the normal segment, the distortion and angle appear, indicating that the tumor is huge in volume, has been invaded or pushed by a large metastatic lymph node, and the possibility of resection is small.
3 The location and depth of the lesion in the lesion: If the ulcer is on the left side of the middle esophagus, or the depth is beyond the boundary of the esophageal wall, it means that the tumor has invaded the mediastinum, or is about to be perforated into the lungs, bronchi Even the aorta, resection (especially radical resection) is less likely.
4 with or without soft tissue shadow: If a large soft tissue mass in a normal X-ray image or CT pushes the trachea, bronchi, pericardium or wrapped around the aorta more than a quarter of a circle, the possibility of resection becomes smaller.
5 pain symptoms: If the patient has severe chest and back pain, it means the lesion has been invaded and the mediastinal pleura and other sensitive organs, the resection may not be large.
(3) Type of surgery:
1 radical esophageal cancer resection and esophageal reconstruction: esophageal cancer is relatively limited, can remove the tumor and its draining lymph nodes to obtain a complete resection of esophageal cancer, it can be regarded as radical surgery. Because esophageal cancer has multiple primary tumors and the biological characteristics of submucosal spread, the length of the upper resection is insufficient to cause residual cancer cells in the margin, and anastomotic recurrence can occur after operation. Therefore, it is suggested that all esophageal squamous cell carcinoma should be performed subtotal esophagectomy. If it is possible to remove, the edge should be 10cm away from the tumor. Esophageal cancer often has external invasion, and the fat connective tissue around the tumor should be removed as much as possible. Radical surgery should include the removal of regional lymph nodes. For the early esophageal cancer, the chest can be removed, and the esophagogastric anastomosis can be performed on the neck by blunt dissection or varus extraction through the neck and abdominal incision. It is beneficial to patients with poor general condition, frail elderly, cardiopulmonary dysfunction, and inability to tolerate thoracotomy. Once the neck anastomosis occurs, the infection is limited and does not pollute the chest.
2 palliative surgery: esophageal cancer is advanced, with tight adhesion to surrounding organs or extensive lymph node metastasis, although the tumor can be removed, but the surrounding infiltration and metastatic lymph nodes often can not be completely removed. Those who cannot undergo radical surgery and have high dysphagia may be given local resection to solve the problem of eating, providing conditions for radiation therapy and chemotherapy. If the tumor can not be removed, only the reduction surgery can be performed. Commonly used esophageal shunt or esophageal lumen management to temporarily solve the patient's diet, and then perform radiotherapy or chemotherapy. Gastric fistula is of little benefit to the patient and is used sparingly.
A. Esophageal shunt: When the thoracotomy was explored, the tumor could not be removed. If the patient had severe difficulty in swallowing, a thoracic esophageal shunt could be used. According to the location of the primary tumor, esophagogastric anastomosis was performed on the upper aortic arch of the cancer or under the arch. The anastomosis method was performed by longitudinally incising the esophagus and the stomach for lateral anastomosis at 2 cm above the tumor. If the upper and middle esophageal cancers are estimated to have a small possibility of resection, but there is severe dysphagia, a colon-free esophageal shunt is used. The abdominal incision was used to transplant the colon through the anterior sternum or the sternum for colonic esophagus and colonic anastomosis.
B. Esophageal lumen tube surgery: patients with poor general condition and unsuitable for thoracotomy. It is estimated that patients with esophageal cancer who cannot be removed or surgically explored can be treated with dilated esophagus of plastic tube or rubber tube of appropriate length and appropriate thickness. The tube is then placed in the stenosis to temporarily relieve difficulty swallowing or aspiration. The upper end of the commonly used pipe is thicker in funnel shape, placed above the narrow to prevent falling off, and the lower part is thin, passing through the narrow part. The catheterization method can be pushed through the oral cavity and placed through the esophagus. The main disadvantage is that the esophageal perforation may occur when the esophagus is dilated. Another method is to introduce the guide into the stomach through the esophagus, and guide the catheter through the incision of the anterior wall of the stomach. The advantage is that the catheter is reliable, and complications such as perforation of the esophagus are not easy to occur. Esophageal cancer that cannot be removed after thoracotomy can be inserted through an esophagectomy.
C. Gastric fistula: Gastric fistula is feasible in patients with advanced esophageal cancer who have severe obstruction and cannot tolerate resection. A commonly used method is Stamm gastrostomy. Make 2 sets of purse-string sutures on the near side of the anterior wall of the stomach, puncture the center of the suture, insert a soft rubber tube with a diameter larger than 1cm into the stomach, and fix the stomach wall and the peritoneum after ligating the suture. The hose is taken out of the body through a puncture of the abdominal wall, and tube feeding can be started after 24 hours. Another Beck Jianu method for permanent gastrostomy, the stomach is cut and slit into a stomach tube, and is pulled out through the abdominal wall of the abdominal wall. The operation is complicated. It is better to insert a rubber tube when feeding. It is better to use Stamm surgery. . The survival of advanced esophageal cancer after gastrostomy is usually about 3 months.
There are many surgical approaches for esophageal cancer and cardiac cancer. Reasonable incision should be as far as possible to completely eradicate the primary tumor, thoroughly clean the draining lymph nodes, safe operation and reduce surgical complications.
(4) surgical methods:
1 thoracotomy:
A. Left thoracotomy: Applicable to most patients with lower esophageal thoracic, cardia and most of the chest. The advantages are as follows: a. The lesions in the middle part of the chest and below are exposed, and the operation is easy and the lesion is removed. b. Facilitate the handling of emergencies related to the aorta. Thoracic lesions often have different degrees of adhesion to the aortic arch and descending aorta. This incision is best for the aorta. Once accidentally injured, it is easy to repair and stop bleeding under direct vision. c. It is convenient for chest and abdomen operation, and reconstruction of the neck and chest at different heights. d. It is convenient to extend the operation to the abdominal cavity into a chest and abdomen joint incision.
B. Thoracic and abdominal combined incision: It has the advantages of open chest and open surgery, and it is well exposed, which is good for anatomy and anastomosis. In the operation of cardiac cancer, more and more cases of abdominal organ involvement were found. At this time, some or all of the organs in the abdominal cavity should be removed to achieve relative or complete cure, such as the removal of organs such as the whole stomach, spleen and pancreas. However, some people think that this procedure is traumatic and affects the patient's respiratory function, which is not conducive to postoperative recovery. More notably, the incision had some difficulty in removing the enlarged mediastinal lymph nodes and could not achieve the purpose of thorough cleaning.
C. Right thoracotomy: the Ivor-Lewis incision and its variants. The common surgical procedure is right thoracic, abdominal median, and cervical three incisions. It is suitable for upper thoracic cancer and partial thoracic cancer. Because there is no aortic arch obstruction, the lesion and even the full length of the esophagus and its surrounding tissue are good for anatomical dissociation; the neck, chest and abdomen lymph nodes can be thoroughly cleaned, the curative effect is better, more in line with the principle of tumor resection; Less interference. Disadvantages: It is very difficult to complete the operation of the neck, chest and abdomen in one position. It is necessary to change the position after the operation in the chest for abdominal dissection and neck anastomosis. Some surgeons also perform secondary disinfection and draping in this process, which is complicated and time consuming. Some people also think that this type of surgery is more traumatic and has a longer operation time, and is not suitable for patients with poor physical condition.
2 non-thoracic surgery:
A. Neck and abdomen incision: According to different resection methods, there are esophageal varus extraction and esophageal exfoliation. The cardiopulmonary interference is small, the postoperative recovery is fast, and those patients with poor cardiopulmonary function and difficult to tolerate thoracotomy can also undergo surgery. For those patients with early lymph node metastasis, esophageal cancer and cardia cancer can achieve both resection and no thoracotomy. Purpose; can also be used as the best way to explore cervical esophageal cancer, is a good incision selected at the right time. Disadvantages: the non-direct vision of the free esophagus makes it possible to have intrathoracic hemorrhage or even massive hemorrhage. Under the premise of preparing for thoracotomy, those with neck and abdominal incision can completely remove the lesion, or the lesion is still limited to the esophageal mucosa. Early patients with submucosal layers were used as exfoliation subjects. In addition, it is controversial because it is impossible to clean the mediastinal lymph nodes.
B. Open the sternal approach in the middle: based on the neck and abdomen incision, in order to complete the anatomy of the upper or lower esophagus under direct vision, the upper or lower part of the sternum is “T” shaped to open or the sternum is full length. Open, avoiding some of the defects of the former.
C. Upper abdomen midline incision: only certain indications for patients with cardiac cancer whose lesions have not invaded the lower esophagus and are not suitable for thoracotomy. The trauma is small, the cardiopulmonary interference is light, and the postoperative recovery is fast. When the lesion is found in the lower part of the esophagus, it is easy to change into a chest and abdomen joint incision. However, the length of the upper margin was not satisfactory, and the anastomosis was difficult.
(5) Complications and management: Esophageal cancer resection, complicated operation, long operation time and large trauma, so there are many complications (Table 6), some of which may directly threaten the life of the patient. According to recent literature reports at home and abroad, the mortality rate of this operation is still high, so attention should be paid to the prevention and treatment of complications.
1 anastomotic leakage: esophageal cancer resection, esophagus and stomach or intestine anastomosis, the contents of the digestive tract overflow from the anastomosis mouth is anastomotic leakage. The reported rate in China is around 3% to 5%, and the mortality rate is 30% to 50%. In recent years, the mortality rate has decreased, but it is still 20% to 30%. The causes of anastomotic leakage include excessively damaging the nutrient vessels of the esophagus and stomach, or suture cutting the esophageal wall, or necrosis of the stomach wall or esophageal wall caused by the stomach wall, improper suture, improper postoperative treatment, etc. Caused by. Early and middle-stage sputum often exhibits relaxation heat, and late stage is persistent low fever. There are symptoms of systemic poisoning, chest tightness, difficulty breathing, and circulatory failure. Chest examination has a fluid and chest sign. In the case of the above-mentioned symptoms, the X-ray film has a liquid pneumothorax in 1 week, and the smear or acid odor turbid liquid and gas are extracted through the chest, and even food residue can be confirmed. Early cockroaches are rare. In the middle and late stage of treatment, if the chest cavity has adhesions, you can do effective thoracic closed drainage, supportive therapy, fasting, high vein nutrition, and jejunum ostomy if needed. More than half of conservative treatments can preserve life and sputum healing. The time of occurrence of sputum is short, the infection in the chest is light, the length of the chest and stomach is allowed to be resected and anastomosed, the fistula is large, or the perforation of the esophagus or local necrosis of the stomach is feasible.
2 empyema: the incidence rate is between 1% and 4%. Because of the difficult operation of esophageal cancer, the operation time is long, and the open-ended anastomosis has a lot of opportunities to contaminate the chest cavity, or it is related to the patient's frail age, low resistance, and untimely treatment of liquid pneumothorax and lung collapse. If postoperative empyema is present, the body temperature gradually rises after the drainage tube is pulled out, the pulse is fast, the shortness of breath is aggravated, and even the respiratory distress, and the pleural effusion fluid and X-ray findings, the thoracic puncture draws a light red slightly turbid liquid, and finally You can diagnose by taking out the pus. In addition to systemic application of antibiotics, blood transfusions, closed drainage should be performed early on diffuse empyema. Localized empyema, intermittent pus, flushing the chest and injecting antibiotics. If the abscess is large, multiple punctures will not be reduced, and the pus will gradually become thicker. It is feasible to use low-grade thick tube drainage. A few patients who are still unable to cure may consider thoracoplasty or pleural fibrous exfoliation.
3 pulmonary complications: one of the common complications after surgery, more common are bronchitis, atelectasis, lung purulence and pulmonary embolism. It is characterized by cough and cough, increased sputum volume, elevated body temperature, shortness of breath, and a voice in the lungs. Treatment is mainly to encourage and assist patients with drainage, ultrasound nebulization, oral tincture and nasal catheter suction.
4 cardiovascular complications: the incidence rate is about 1%, and abroad is as high as 2.2% to 18.9%. Patients with severe cardiovascular complications are cardiac arrest caused by postoperative myocardial infarction. Mainly manifested as palpitation, shortness of breath, sitting breathing, pulse weak, low blood pressure, arrhythmia, congestive heart failure or acute pulmonary edema. Diagnosis mainly depends on cardiac X-ray and electrocardiogram examination, and sometimes venous pressure measurement. Treatment should be based on a reasonable treatment plan with the cardiologist to treat.
5 chylothorax: due to the damage to the thoracic duct, causing the chyle to leak into the chest cavity. The incidence rate is 0.4% to 2.6%. If not treated in time, it can cause serious consequences and endanger life. Conservative treatment can be used first, and some patients can be cured. It has been suggested that surgical treatment of chylothorax caused by surgery is appropriate.
6 postoperative sputum: the incidence rate is below 1%. Mainly due to the operation of the reconstruction of the palpebral fissure when the channel is too large, or the diaphragm, sputum and stomach fixed suture avulsion, so that the abdominal organs into the chest, compression, or gastrointestinal obstruction, the most common sputum into the organ is the colon and spleen. X-ray examination showed that there were single or multiple fluid levels of different sizes in the thoracic cavity, which changed with the change of body position. Barium enema or digestive tract angiography can confirm the diagnosis. Treatment should be performed in time to repair the holes.
7 Traumatic shock: This type of complication is rare. It occurs mostly in old and weak, and the general situation is worse. The use of anti-shock treatment, the right measures can achieve the effect of turning to safety.
8 long-term complications: common anastomotic stenosis and reflux esophagitis. The incidence of anastomotic stenosis is about 1% or less, and the degree of stenosis can be divided into mild (0.5-0.8 cm, can enter semi-fluid), moderate (0.3-0.5 cm, can only enter fluid) and severe (0.3 cm or less, The influx is also difficult or dripping.) Stenosis can be used for treatment, and those who fail to maintain nutrition after repeated expansion failure can be treated with surgery. Generally, it is cut from the stomach side, and the stenosis is removed and anastomosis is performed. Reflux esophagitis is caused by reflux of gastric acid from the stomach to the esophagus, causing anastomotic edema, inflammation, and even anastomotic ulcer. Generally, conservative treatment can be used to cure.
(6) The important factors affecting the long-term survival after esophageal cancer resection: the early resection rate of esophageal cancer is 100%, the 5-year survival rate is about 90%, and the mid-to-late stage reports are different. The 5-year survival rate is 30. %the following. The important factors affecting the long-term survival after esophageal cancer resection are lymph node metastasis, depth of invasion, staging and margin of resection. The relationship between TNM staging and 5-year survival rate of esophageal cancer.
2. Chemotherapy of esophageal cancer In the past, esophageal cancer was considered to be insensitive to chemotherapy. Chemotherapy is only used in patients who cannot undergo surgery and radiotherapy, and most of them use a single drug. Due to extensive lesions, patients have poor general condition and many complications, so the curative effect is generally better. difference. Since the 1980s, cisplatin has been widely used in esophageal chemotherapy, especially in combination with multiple drugs. The efficacy of chemotherapy for esophageal cancer has been significantly improved, the remission period has been prolonged, and some cases have achieved complete remission. This gives chemotherapy for esophageal cancer. With new vitality and hope, chemotherapy is not only used to treat advanced esophageal cancer, but also as a component of neoadjuvant chemotherapy (pre-chemotherapy), which can significantly increase the surgical resection rate of patients with advanced esophageal cancer and prolong the patient. The lifetime.
(1) Indications and contraindications:
1 indications:
A. Patients who are not suitable for surgery or radiotherapy.
B. Patients with advanced and extensive metastases, as long as the general condition is good, the bone marrow and heart, liver, lung and kidney functions are basically normal. They can enter the semi-liquid diet or above. Chemotherapy and supportive therapy can be used. After a certain degree of remission, take Other therapies.
C. As adjunctive therapy before and after surgery or radiotherapy and treatment of tumor recurrence and metastasis after surgery or radiotherapy.
2 contraindications:
A. Old and frail or cachexia patients.
B. Serious heart, liver, lung, kidney function disorders, accompanied by infection, fever, esophageal bleeding or perforation.
C. Low bone marrow function, less than 3 × 109 / L white blood cells, less than 5 × 1010 / L platelets, severe anemia or bleeding tendency.
(2) Efficacy criteria: advanced esophageal cancer progresses rapidly, and the evaluation of curative effect is very difficult. It is not enough to evaluate the curative effect based on symptomatic relief, because in addition to chemotherapy, symptoms such as antibiotics, dehydration, acupuncture and psychotherapy can be used. Short-term relief symptoms. In 1984, Kelsen proposed the evaluation criteria for chemotherapy efficacy of esophageal cancer: A. Complete remission: The esophageal sputum meal showed complete retraction of the tumor, no tumor was seen by endoscopy, and cytology turned negative. For preoperative chemotherapy, surgical specimens should have no tumor residual, no lymph node metastasis, no distant metastasis; B. partial remission: tumor retraction greater than 50% and less than 100%, endoscopic or surgical seeing residual tumor under the naked eye or microscope; C. Mild relief: tumor regression shrinks to 50%.
(3) Single-agent chemotherapy: Chemotherapy for esophageal cancer in the 1960s and 1970s was based on a single drug. The subjects were patients with advanced esophageal cancer. The most commonly used drugs were bleomycin (BLM) and mitomycin (MMC). ), doxorubicin (doxorubicin),Methotrexate(MTX), vindesine (vinblastine amide), fluorouracil (5-Fu), lomustine (cyclohexyl nitrosourea),Etoposide(Ghost 臼 甙 甙), Mito 胍腙 (Ami 腙 腙), etc., the efficiency of each report is different, but most of them are below 20%. In the 1980s, cisplatin (DDP) was applied to the treatment of esophageal cancer with an efficiency of more than 20%. In 1985, Miller reported that 15 cases of esophageal cancer were treated with DDP, with an effective rate of 73%. New chemotherapy drugs for esophageal cancer have also been reported. Conroy reported the use of vinorelbine (Vinoribin, Navelbin) in the treatment of metastatic esophageal squamous cell carcinoma, the effective rate was 25%; Ajani et al used paclitaxel in 42 patients with esophageal cancer, 13 patients were partially relieved, the effective rate was 31% Of the 30 adenocarcinomas, 10 were effective (33%) and 3 of the 12 squamous cell carcinomas were effective (25%). The effects of single drug treatment for esophageal cancer are reported by different authors (Table 8).
(4) combined chemotherapy: single drug chemotherapy has a shorter remission period, often combined with multiple drugs. Most of the combined chemotherapy used cisplatin (DDP) and bleomycin (BLM)-based combination chemotherapy, compared with single drug chemotherapy, its efficiency was significantly improved, the remission period was prolonged, but its side effects were also significantly increased. Patients receiving chemotherapy should have a Karnofsky index of 50 or less, and should not be used in critically ill patients. Combination chemotherapy is not only suitable for the treatment of advanced esophageal cancer, but also for the comprehensive treatment of surgery or radiotherapy. The following are some of the major chemotherapy regimens reported in the literature.
1DDP-VDS-BLM solution:
Cisplatin (DDP): 3 mg/kg, day 1, intravenous.
Vindesine (VDS): 3 mg/m2, 1, 8, 15, 22 days, intravenously.
Bleomycin (BLM): 10 mg/m2, day 3-6, intravenous injection.
On the 29th day, the course of treatment was repeated. After the second course of treatment, cisplatin (DDP) was given once every 6 weeks. VDS was once every 2 weeks and was no longer maintained with bleomycin (BLM).
2DDP-BLM solution:
Cisplatin (DDP): 3 mg/kg, day 1, intravenous.
Bleomycin (BLM): 10 mg/m2, day 3-6, intravenous injection.
The second course of treatment begins on the 29th day, and the third course of treatment is 6 to 8 weeks.
3DDP-BLM-MTX:
Cisplatin (DDP): 50 mg/m2, day 4, intravenous injection.
Bleomycin (BLM): 10 mg/m2, days 1, 8, 15 intravenously.
Methotrexate (MTX): 40 mg/m2, day 1, 14 intravenously.
Repeat the treatment every 3 weeks.
4DDP-BLM-VPl6 solution:
Cisplatin (DDP): 80 mg/m2, day 1, intravenous injection.
Bleomycin (BLM): 10 mg/m2, day 3, intravenous injection; or day 3 to 5, continuous infusion for 24 hours.
Etoposide (VP-l6): 100 mg/m2, 1, 3, 5 days, intravenous injection.
5DDP-BLM-VCR-5-Fu solution:
Cisplatin (DDP): 50 mg/m2, day 1, intravenous.
Bleomycin (BLM): 10 mg, 1 to 3 days, once every 8 hours, intravenous injection
Vincristine (VCR): 1.4 mg/m2, day 1, intravenous.
Fluorouracil (5-Fu): 500 mg/m2, on days 1 to 5, intravenously.
7DDP-ADM-5-Fu solution:
Cisplatin (DDP): 75 mg/m2, day 1, intravenous injection.
ADM: 30 mg/m2, day 1, intravenous injection.
Fluorouracil (5-Fu): 600 mg/m2, day 1, 8 days, intravenous injection.
8DDP-5-Fu solution:
Cisplatin (DDP): 100 mg/m2, day 1, intravenous injection.
Fluorouracil (5-Fu): 1000 mg/m2, day 1 to 5, intravenous injection.
9DDP-VDS-MeGAG program:
Cisplatin (DDP): 120 mg/m2, day 1, intravenous injection.
Vindesine (VDS): 3 mg/m2, once a week for 4 weeks, intravenously.
Mitoxantrone (Cymidine): 500 mg/m2, day 1, intravenous injection.
10BLM-ADM program:
Bleomycin (BLM): 15 mg/m2, day 1, 4, intravenous injection.
ADM: 40 mg/m2, 2nd, 3rd day, intravenous injection.
Repeat the treatment every 3 weeks.
?DDP-VCR*-PYM* program
Cisplatin (DDP): 20 mg/m2, days 1 to 5, intravenously, repeated 3 to 4 weeks later.
Vincristine (VCR): 2mg/m2, 3 times a week for 7 weeks (8-9 am), intravenous injection.
Pingyangmycin (PYM): 10 mg/m2, 3 times a week for 7 weeks, intramuscular injection (3 to 4 pm on the same day with VCR).
?DDP-MMC-PYM program:
Cisplatin (DDP): 20 mg/m2, day 1 to 5, repeated 3 weeks later, intravenously.
Mitomycin (MMC): 6 mg/m2 once a week for 7 weeks.
Pingyangmycin (PYM): 6 mg/m2, 3 times a week for 7 weeks, intramuscular injection.
?DDP-5-Fu-BLM scheme:
Cisplatin (DDP): 30 mg/m2, day 1, 8 days, intravenously.
Fluorouracil (5-Fu): 1000 mg/m2, day 1 to 5, intravenous injection.
Bleomycin (BLM): 10 mg/m2, twice a week, intravenously.
Cisplatin (DDP) and fluorouracil (5-Fu) are repeated once every 3 weeks, depending on the patient's condition, 9 to 12 weeks, and bleomycin (BLM) can be used for 9 to 12 weeks.
?DDP-CF*-5-Fu solution:
Cisplatin (DDP): 40 mg/m2 for 3 days, intravenously.
Tetrahydrofolate (CF): 30 mg/m2 for 5 days, intravenous injection.
Fluorouracil (5-Fu): 1000m/m2, for 5 days, intravenous injection.
One course every 3 weeks.
(5) Multimodality Therapy: The effect of using a single method to treat esophageal cancer is unsatisfactory. Although surgical treatment is still the main method for the treatment of esophageal cancer, most of the patients who have been treated have lost the opportunity for surgery, and the 5-year survival rate of surgical resection alone is only about 10%. The effect of using radiotherapy alone is also unsatisfactory. This is not surprising, as surgery and radiotherapy can only control local tumors and are ineffective for metastases that may exist at the time of diagnosis. Therefore, these two treatments are limited to the primary tumor, and treatment of tissues close to the esophagus may be ineffective, prompting many researchers to use local treatment combined with systemic chemotherapy to control non-clinical metastases. At present, Neoadjuvant Chemotherapy, which precedes chemotherapy before topical treatment, has become an important means of multi-modal treatment of esophageal cancer.
1 Chemotherapy-surgical treatment: Many non-randomized controlled clinical studies have shown that preoperative chemotherapy can not only improve the surgical rate of advanced esophageal cancer, but also significantly increase the median survival of patients (Table 9, 10). On the other hand, almost half of the patients are not sensitive to chemotherapy. Preoperative chemotherapy in such patients will prolong the operation time of the patient and increase the distant metastasis rate of the tumor. Therefore, whether preoperative chemotherapy can increase the long-term survival rate of patients, it is very necessary to conduct a rigorous clinical randomized controlled study.
A randomized controlled trial from Roth and Schlag showed that the response of the combination treatment group to chemotherapy was only 47%. Compared with the surgery alone group, the comprehensive treatment did not improve the median survival of the patients, although the comprehensive treatment in Roth's study 3 The annual survival period is longer than that of surgery alone, but most of them are patients who are sensitive to chemotherapy before surgery. Schlag's study had to stop the experiment midway because of the increased mortality from reoperation after chemotherapy. In the Nygaard study, the 3-year survival rates of the surgery-only and comprehensive treatment groups were 9% and 3%, respectively.
In conclusion, about half of the patients undergoing chemotherapy-surgical treatment are not sensitive to chemotherapy. Due to the small number of studies, randomized controlled studies in the literature do not show the superiority of this comprehensive treatment. Research is ongoing.
2 Chemotherapy-radiotherapy: Since the discovery of radiosensitization effects of cisplatin (DDP), fluorouracil (5-Fu), mitomycin (MMC) and other chemotherapeutic drugs, many scholars have explored the use of chemotherapeutic drugs as radiosensitizers and radiotherapy. Combined use in the treatment of esophageal cancer has yielded encouraging initial results. In 1990, Sichy et al reported randomized radiotherapy combined with radiotherapy and fluorouracil (5-Fu) and mitomycin (MMC) 60Gy radiotherapy for the treatment of esophageal cancer. The median survival of the comprehensive treatment group was significantly higher than that of the radiotherapy group alone (14.8 months vs. 9.1 months, P <0.05); and randomized studies by Herskovic and Al-Sarraf et al showed a median, 2-year and 3-year survival rate in the cisplatin (DDP) and fluorouracil (5-Fu) 50Gy radiotherapy combined treatment group They were 14.1 months, 36%, and 30%, respectively, while the radiotherapy group was 9.3 months, 10%, and 0. The difference between the two groups was very significant (P < 0.0001). The above studies have shown that for patients with advanced esophageal cancer who have lost their chance of surgery, as long as the patient's general condition allows, chemotherapy and radiotherapy will have a significant effect on improving the long-term survival rate of patients. Foreign scholars will combine radiotherapy and chemotherapy. Radiotherapy alone was compared.
This shows that the combination of radiotherapy and chemotherapy is better than radiotherapy alone. Radiotherapy usually uses a radical dose, and the choice of chemotherapy drugs varies. Table 13 describes several commonly used treatment options.
3 chemotherapy-radiotherapy-surgical treatment: Forastiere treated 43 patients with advanced esophageal cancer with DDP/VBL/5-Fu regimen, in which fluorouracil (5-Fu) continued intravenous infusion for 21 days [300mg/(m2·d)] Cisplatin (DDP) and VBL were used for 10 days to achieve the best radiosensitivity, and 45Gy radiation was given for 3 weeks. The results showed that 95% of the 43 patients underwent surgery again. The tumor resection rate was 84. %, median survival was 29 months, 2-year and 5-year survival rates were 57% and 34%, respectively, while Orringe reported 100 patients with esophageal cancer treated with single-surgery, with a median survival of 12 months, 2 years The 5-year survival rate was 32% and 17%, respectively, which was significantly lower than the former. Forastiere recently reported the use of cisplatin/fluorouracil (DDP/5-Fu) and radiation therapy in 50 patients with esophageal cancer (33 adenocarcinoma, 16 squamous cell carcinoma, 1 undifferentiated carcinoma) with an operation rate of 94%. The resection rate was 90%, and 40% of patients achieved complete remission with a median survival of 31 months and a 2-year survival rate of 58%. Long-term follow-up is ongoing.
Randomized study also showed that the combined treatment effect of chemotherapy, radiotherapy and surgery was significantly higher than that of a single treatment. 100 patients with esophageal cancer (75 cases of adenocarcinoma, 25 cases of squamous cell carcinoma) were randomly divided into two groups. One group was treated with surgery alone, the other was treated with chemotherapy and radiotherapy, and then the surgery was performed. The results showed that the pathological response rate of the two groups was At 28%, the median survival time was 12 months, but the follow-up rate was 5.6 years. The long-term survival rate of the comprehensive treatment group was significantly higher than that of the surgery group alone, suggesting that comprehensive treatment has a significant effect on improving the survival of patients with advanced esophageal cancer. .
3. Endoscopic treatment
(1) endoscopic resection of early cancer: in recent years, due to the improvement of endoscopy techniques and the application of electronic endoscopy and chromoendoscopy techniques, especially the large number of epithelial cancers and intramucosal cancers, for early cancer There is a new understanding of biological characteristics and endoscopic features. On this basis, a new perspective has been put forward on the treatment of early cancer: surgery is not the only means to treat early cancer. Some intraepithelial and intramucosal cancers can also achieve good results by endoscopic resection, so endoscopic treatment can be considered first for early esophageal cancer.
1 indications:
A. Early-stage cancer lesions are highly differentiated <2 cm, and poorly differentiated types are less than 1.5 cm.
B. Surgical high-risk patients in early-stage cancer cases, including those who are old, infirm, and have serious organ diseases.
C. Those who refuse to open the chest or open surgery.
D. Severe dysplasia or moderate to severe dysplasia and the naked eye is suspected of being malignant.
2 preoperative preparation and postoperative treatment: A. preoperative preparation with conventional endoscopy, preoperative intramuscular injection of atropine 0.5mg and diazepam (diazepam) 10mg. B. According to the size of the lesion, choose a reasonable treatment method and corresponding supporting equipment, such as double-clamp treatment endoscope, high-frequency electrocautery, microwave therapy instrument, laser therapy instrument and related drugs. C. Comprehensive preoperative examination to exclude liver, lung and supraclavicular lymph node metastasis. D. Perform endoscopic ultrasonography as much as possible before surgery to understand the depth of invasion and lymph node metastasis. E. Good mucosal staining before surgery is very important for accurate resection of the lesion. Before the staining, the mucus and the moss film on the surface of the lesion were washed with an antifoaming agent, and then stained. Lugol solution or toluidine blue solution counterstaining can show clear outlines of early esophageal cancer and severe dysplasia, which is conducive to accurate resection. F. After fasting and infusion for 3 to 5 days, if the lesion is located in the cardia or the lower end of the esophagus, antacids and gastric motility drugs should be applied to reduce the erosion of gastric juice by the reflux of gastric juice. Wound ulcers can heal 2 to 4 weeks after surgery. Endoscopic follow-up was performed at 1, 3, and 6 months after surgery.
3 endoscopic treatment methods:
A. Endoscopic high-frequency electric ring sleeve resection method: This is a conventional treatment method for gastrointestinal polyps, and is also suitable for the treatment of pedicled polypoid esophageal cancer. The biopsy confirmed that the posterior lens found a polypoid tumor, and the snare was placed on the base for high-frequency electrical resection. To prevent bleeding, the pedicle should remain 0.5 cm. In the case of a thick pedicle, it may be safer to increase the time of electrocoagulation or to inject a small amount of hardening agent (such as 50% sodium cod liver oil) into the pedicle.
B. Endoscopic exfoliation biopsy: a combination of endoscopic local injection and polypectomy. Several milliliters of para-adrenalin saline was injected into the base of the lesion to cause the lesion to bulge, and then the lesion, the periorbital and submucosal tissue were removed by high frequency electricity. The purpose of injecting para-adrenalin saline is to promote submucosal swelling and increase the distance between the lesion and the muscular layer to ensure that the muscle layer is not damaged during resection. It is generally believed that there is no significant difference in the efficacy of endoscopic biopsy in early cancer compared with surgery. This endoscopic treatment method is considered to have practical value.
C. Endoscopic double-segment polypectomy (endoscopic resection): Apply double-clamp endoscope, first use biopsy forceps to lift the lesion, then use the snare to cover the base of the lesion, and then electrocoagulation.
D. Local Hypertonic Saline and Adrenalin Injection Endoscopic Radical Surgery (ERHSE): Find the lesion, spray the pigment to determine the extent of the lesion, make a point incision 0.5cm in the periphery of the lesion, mark the scope of the resection. Then submucosal injection of hypertonic saline and adrenaline mixture (usually 3.7% sodium chloride 10ml or 10% glucose normal saline 10ml plus 0.1% adrenaline 1ml), so that local swelling bulge, and then another forceps from the endoscope The crossing extends out of the snare for electrocoagulation. This method can prevent intraoperative bleeding, and can increase the distance between the lesion and the muscular layer to ensure the safety of the operation. The tissue block excised by this method is large and deep, and the lesion of more than 2 cm can also be continuously removed by this method.
E. Capped endoscopic resection (EMRC): The principle of endoscopic ligation with esophageal varices is basically similar. The specific operation is as follows: a transparent endoscope cap with the same aperture as the endoscope is mounted on the front end of the endoscope, and the length is about 1 cm. Before the mucosal resection, 10 ml of adrenaline normal saline was injected under the mucosa to make the lesion bulge. The negative mucus was sucked into the end cap of the lens, and then the lesion was grasped by a snare to perform high-frequency electric resection.
F. Mediastinal peeps under esophagectomy (MMDE): This is a new development technique. West Germany Bumm used this technique to treat 16 cases of lower esophageal cancer without complications and death. A specially designed mediastinoscope is used at the tip with a dilator that opens the anatomical channel and a miniature camera that connects the fiber beams to observe the structure inside the mediastinum. The operation was performed from the left side of the neck to the mediastinum and then the esophagus was removed. There are no reports in this regard in China.
Endoscopic treatment of early cancer is similar to surgical resection, and endoscopic treatment does not require chest opening or laparotomy, which is far simpler and safer than surgery. Therefore, the value of early cancer treatment in endoscopic surgery has been valued. However, endoscopic treatment of early cancer has a limited range of applications. Not every early cancer can completely eradicate the lesion, especially if it is difficult to judge the depth of invasion and lymph node metastasis before surgery, and there is no power for deep infiltration and metastasis. Despite this, this method is still a valuable treatment for intraepithelial, intramucosal, and certain surgical contraindications. If you can strictly control the indications, supplemented by endoscopic ultrasonography, and master the endoscopic treatment technology, it will inevitably get good results.
(2) endoscopic treatment of advanced esophageal cancer: at present, endoscopic local injection of anticancer drugs, endoscopic laser, microwave, endoscopic esophageal dilatation, endocytosis, etc. for palliative of middle and advanced esophageal cancer Treatment has been widely adopted and has achieved certain effects.
1 Endoscopic local injection of anticancer drugs: suitable for middle and advanced esophageal cancer that cannot be surgically removed, and can also be used for early esophageal cancer that is not suitable for surgery or refuses surgery. The method has the advantages of high local drug concentration, long acting time, good curative effect and small systemic side effects. Moreover, lymphatic drainage can be used to treat the corresponding lymph nodes. For the treatment of advanced esophageal cancer, mitomycin (MMC) 2 ~ 4mg + fluorouracil (5-Fu) 250 ~ 500mg + bleomycin (BLM) l0mg, diluted into 10 ~ 20ml suspension on the tumor in the tumor The central base and the edge are infiltrated with multiple points. Ulcer type is inserted at the edge of the ulcer 2 to 3 cm, 0.5 to 1.0 ml per point, once a week, 6 to 8 times for a course of treatment. For early esophageal cancer, submucosal injection of the tumor and surrounding points, 0.5ml per point, the total amount of about 2.5ml each time. Care should be taken to avoid complications such as deep ulcers, bleeding, and perforation.
2 Endoscopic laser treatment of laser: Nd:YAG has been a very successful mitigating benefit in the treatment of esophageal cancer. Esophageal cancer, which is confined to the mucosa and even the submucosal, may be cured by laser, but it is still under investigation. The histological effect caused by the Nd:YAG laser is related to the temperature generated by the laser. The solidification effect occurs when the temperature is average at 60 ° C; vaporization and cutting occurs when the temperature reaches 100 ° C. 90% of patients with advanced esophageal cancer can achieve functional improvement after laser treatment, thereby enhancing nutrition and improving physical fitness. 60% to 80% of patients can swallow solid food, the preferred length of laser treatment should be less than 8cm, which is the best for mid-stage polypoid cancer. It is less effective for large submucosal long-form cancer. The treatment of cervical esophagus is difficult and the chance of remission is low, but patients with recurrence after esophagogastric anastomosis are easily relieved by laser treatment. Functional improvement is generally maintained for four weeks, so multiple treatments are required and some patients are difficult to tolerate.
Laser treatment has fewer complications, including bleeding, perforation, and esophageal fistula. However, as long as the indications are mastered and the operating rules are strictly observed, serious complications such as perforation can be avoided.
3 Photodynamic therapy (PDT): The experience of using PDT to treat esophageal cancer in the past 10 years shows that the best effect of early superficial lesions is better, but the upper stage lesions are far more effective than laser to relieve dysphagia. Hematoporphyrin-laser-sensitive therapy is based on the concentration of hematoporphyrin derivative (HPD) in cancer tissues, and the tumor tissue that induces hematoporphyrin is excited by laser irradiation to produce singlet oxygen to destroy tumor cells. However, the entire treatment should be performed in a dark room to prevent solar dermatitis. Intravenous injection of porfumer sodium 2mg/kg, injected within 3 to 5 minutes, the patient stayed in the dark room for 40 ~ 50h and then treated with low-energy laser. If the patient can tolerate, it can be repeated once with laser after 96-120 hours after intravenous infusion. Guangfuin intravenous injection can be repeated 2 to 3 times, each time interval of more than 30 days. Low energy laser treatment can not exceed 6 times.
4 endoscopic microwave therapy: microwave heating up to 42 ~ 44 ° C, can inhibit the DNA and RNA synthesis of cancer cells, kill cancer cells, but no significant damage to normal cells, and synergistic effect with radiotherapy, can improve Efficacy, reduce radiation dose, reduce radiotherapy response.
5 endoscopic local injection of absolute alcohol: suitable for lesions less than 5cm in length, cancer invasion of mucosa, submucosa or superficial muscle layer, no lymph node metastasis, no radiotherapy and refused surgery. There are 3 to 5 injection sites, all of which have alcohol infiltration, and the depth reaches the whole cancer tissue, so that each site can inject 0.4-0.8ml of alcohol, the total amount does not exceed 4ml, try to avoid normal tissue to reduce the hardening range. And unnecessary narrowing occurs. The entire course of treatment was injected 3 times, at intervals of 2 weeks. If there is no accident after injection, you can enter the liquid diet after 8h, enter the semi-solid food after 24h, and return to normal life after 3 days. This therapy is likely to be one of the most affordable treatment options for patients with early esophageal cancer.
6 endoscopic esophageal dilatation and internal cannulation: the esophageal stenosis caused by esophageal cancer can be dilated by endoscopy, which can relieve the symptoms of obstruction for a long time. Esophageal cancer patients who are not suitable for surgical treatment can be orally administered without gastric fistula, improving the quality of life and survival time of patients. Complications of esophageal dilatation and internal cannulation are bleeding, perforation, and the like. Therefore, the operation should be cautious and careful, and the force should be moderate to avoid complications.
7 Endoscopic Electrochemotherapy: Electrochemotherapy can cause localized electrochemical reactions and changes in tissue structure, destroy the living conditions of tumors, and cause a variety of pathological reactions in cancer cells to achieve the effect of killing tumors. Endoscopic electrochemotherapy for esophageal cancer can rapidly necrosis of tumor tissue, dilatation of anastomotic stenosis, release of mechanical obstruction in the lumen, and oral feeding of patients, rapidly improving the general condition of patients, and improving the esophageal cancer patients who have lost the timing of surgery. Quality of life and prolonged survival. But this method is, after all, a partial, non-radical treatment. When the general condition of the patient is improved, comprehensive treatment measures such as radiotherapy and chemotherapy should be supplemented.
(3) Application of thoracoscopic surgery in the treatment of esophageal cancer: With the improvement of endoscopic instruments and technical skills, the indications for video-assisted thoracoscopic surgery (VATS) are expanding. Some operations that can only be performed in the past have been gradually completed by VATS. Instead, the number and type of surgeries are increasing. VATS is especially suitable for the treatment of middle esophageal cancer resection and lymph node dissection. The choice of VATS surgery should focus on the degree of tumor cure and focus on long-term survival. Thoracic surgery should be performed without hesitation when the thoracoscopic surgery is difficult to achieve. VATS is just a new surgical method, not a new one. It requires changing the traditional concept of open chest surgery and gradually adapting to the operation of the instrument under the monitor. Surgeons should be proficient in chest anatomy and traditional thoracic surgery techniques and have the ability to handle intraoperative complications. After endoscopic surgery, VATS surgery can be performed, and the principle of gradual progression should be mastered to prevent surgical complications.
4. Radiation therapy for esophageal cancer Most patients with esophageal cancer are in the advanced stage, and many of them cannot be treated surgically. Radiotherapy has less damage and is less restricted by important organs and tissues around the esophagus. It has a wide range of applications. Most patients who cannot be operated can still undergo radiotherapy. In many cases, surgery needs to be combined with preoperative or postoperative radiotherapy. Therefore, radiotherapy is One of the main treatments for esophageal cancer, about 80% of patients with esophageal cancer need to use radiation therapy. Radiation therapy for esophageal cancer can be divided into radical radiotherapy and palliative radiotherapy according to the purpose of treatment. It can be divided into external irradiation and intracavitary irradiation according to the treatment method. It can be divided into radiotherapy and comprehensive treatment according to whether it is combined with surgery (preoperative or postoperative) Radiotherapy).
(1) indications and contraindications: radical radiotherapy is the expectation that cancer can be cured, patients may obtain long-term survival. Palliative radiotherapy only hopes to reduce the pain of patients through treatment, mainly to relieve dysphagia and prolong the survival time of patients.
1 indication of radical radiotherapy: the general condition is better, the lesion is shorter than 7cm, no obvious tumor invasion, no serious stenosis of the esophagus (can enter the semi-liquid). There were no obvious signs of perforation on the X-ray film (large ulcers or spikes), silent band paralysis and supraclavicular lymph node metastasis.
2 palliative radiotherapy indications: the general situation is acceptable, still can enter a semi-liquid or liquid diet, X-ray film does not show perforation.
3 radiotherapy contraindications: generally poor or cachexia; complete esophageal obstruction; esophageal perforation or formed fistula; there have been distant metastasis.
Patients with radical radiotherapy or palliative radiotherapy are mainly determined by factors such as tumor stage and patient's physical condition. And the relationship between the two is relative, often adjusted according to the evolution of the condition in the treatment. Some contraindications are also relative. For example, patients with esophageal fistula should seek palliative radiotherapy after a stable stomach or repair. Individuals still have a chance to heal.
(2) Radiation therapy technology:
1 In vitro radiotherapy: A. The choice of radioactive source is mainly 60Go-γ-ray or 4~10MeV high-energy X-ray. For body thickness, higher energy X-ray irradiation can be used. B. Irradiation range and arrangement of irradiation field: The irradiation target area of radiotherapy must include the primary tumor, surrounding subclinical lesions and regional lymph nodes, and the whole target area should be irradiated with high dose evenly. Organs and tissues to avoid serious complications. The length of the esophageal cancer field is generally 3 cm above and below the X-ray lesions. If the lesions on the X-ray film are unclear, the irradiation field may be appropriately longer. The width of the field is usually 5-6 cm, including esophageal lesions and their external invasion sites and lymph nodes adjacent to the esophagus.
There are three main arrangements for the irradiation of esophageal cancer:
A. Before and after the two vertical vertical irradiation method, its advantages are accurate and reliable, but the spinal cord dose is the same as the esophageal dose, mainly used for preoperative radiotherapy or palliative radiotherapy, but not for radical radiotherapy, because of high dose irradiation of radioactive myelitis More likely.
B. Three-field irradiation, that is, the previous vertical field, and the back of the two oblique fields. When the oblique field angle is greater than 50 degrees, the spinal cord is in the range of 50% to 55% dose curve. At the radical dose of 60-70 Gy radiotherapy, the spinal cord dose is below 40 Gy, and the lung tissue dose and the volume being irradiated are both Within the allowable range. The wilderness method is currently considered to be the most reasonable and is widely used in the radiotherapy of lower thoracic esophageal cancer.
C. Second front oblique field, mainly used for esophageal cancer at the level of cervical and thoracic entrance. Two left and right oblique fields with an angle of 100 to 120 degrees, applying a 15 degree or 30 degree wedge plate, and a thick end to the head and the tip to the foot to compensate for the unevenness of the dose due to the high and low contour of the body. The upper and lower doses of the irradiation field were uniform, and the method controlled the spinal cord volume within the 60% isodose curve without exceeding the tolerated dose of 40 Gy. The setting of the irradiation field should be calculated by the simulation positioning machine positioning and treatment planning system to ensure that the tumor receives high dose irradiation, and the dose of the surrounding vital organs such as the spinal cord is within the tolerance range.
The current dose of esophageal cancer radiotherapy is still inconsistent, but most scholars believe that the conventional dose of esophageal squamous cell carcinoma is 60 ~ 70Gy / 6 ~ 7 weeks is appropriate, too high dose of radiation can not improve the efficacy, and complications The occurrence is significantly increased. The palliative treatment dose was 50 Gy/4 to 5 weeks. At least 50 Gy is required to completely kill subclinical lesions. For palliative treatment, unless there is distant metastasis or local lesions are too broad or have signs of perforation, as long as the patient can tolerate, high doses should be given as much as possible to better control local lesions, to minimize symptoms of esophageal obstruction and prolong The patient's survival period and can give some patients a chance to heal.
2 intracavitary radiotherapy: uncontrolled or local recurrence of esophageal cancer is the main cause of radiotherapy failure, which may be due to insufficient radiation dose, and further increase of external dose will lead to serious complications such as heart, lung and spinal cord. Therefore, intracavitary radiotherapy technology has been developed to increase the local dose of esophageal lesions. The radioactive sources used for intracavitary radiotherapy are mainly 192Ir, in addition to 60Co, 137Cs and so on. The current intracavitary radiotherapy uses post-loading technology, that is, the catheter is inserted into the esophagus through the nasal cavity and oropharynx and passed through the lesion area, and then the radioactive source is inserted into the treatment area through the lumen of the catheter according to the pre-determined position of the esophageal lesion. Internal illumination. Intracavitary irradiation is characterized by a high surface dose, and as the depth increases, the dose drops dramatically. Esophageal extra-dose dose is low, and its damage to surrounding tissues is small, but for advanced esophageal cancer, it is not appropriate to use intracavitary treatment alone or mainly.
The main indications for intracavitary radiotherapy are:
A. Early esophageal cancer, superficial lesions.
B. As a supplement to external exposure.
C. Local recurrence after external irradiation, and no external irradiation can be performed.
Intracavitary radiotherapy has a good effect on superficial esophageal cancer in early stage. The Chinese Academy of Medical Sciences Cancer Hospital reported early esophageal cancer with intracavitary radiotherapy. The 3-year survival rate was 48% (13/27); Hashikawa et al reported 6 patients with early superficial lesions. Intracavitary radiotherapy 18 ~ 24Gy endoscopy after 1 month, 6 patients with tumors all disappeared. Only one patient relapsed after 7 months of follow-up, and no recurrence was found in the remaining 5 patients who were followed up for 16 months. The efficacy of in vitro irradiation with intracavitary radiotherapy for advanced esophageal cancer was also improved. A randomized study reported that 70 Gy/7 weeks of external irradiation alone and 50 Gy/15 weeks of external irradiation combined with intracavitary radiotherapy were 18 to 20 Gy/3 to 4 times. The 1-, 2-, and 3-year survival rates of the comprehensive group were 83%, 45%, and 34%, respectively. The external exposure group was 67%, 30%, and 19%, respectively, indicating that the comprehensive group was better than the external group. However, the incidence of radiation esophagitis in the comprehensive group is high, the reaction is heavy, and there are many radioactive ulcers. At present, many problems of intracavitary radiotherapy combined with extracorporeal irradiation in esophageal cancer are still in the research and exploration, such as the choice of cases, the timing of the cooperation, the dose, etc. are still difficult to determine. Some authors suggest that after radical irradiation of 60 ~ 70Gy, X-ray lesions have residual intracavitary radiotherapy 10 ~ 15Gy / 1 ~ 2 weeks, each time 5Gy, dose reference point 1cm outside the radioactive source, roughly equivalent to mucosa Below 0.5cm. In order to study the relationship between dose and efficacy, Sur divided the patients into three groups to receive different doses of radiation: group A 12 Gy divided into two divisions; group B 16 Gy divided into two divisions; group C 18 Gy divided into three divisions. The results are as follows.
(3) Factors influencing the efficacy of radiotherapy: Most cases of radiotherapy for esophageal cancer are patients who are estimated to be inoperable, have contraindications for surgery, or refuse to undergo surgery. Most of them are patients with advanced disease, so the curative effect is poor. The 5-year survival rate is generally 5% to 9%, but the 5-year survival rate of cases can be as high as 16% to 20%. The radiation therapy of early esophageal cancer <3cm is equivalent to the surgical effect.
In addition to distant organs and lymph node metastasis, the main factors affecting the efficacy of esophageal cancer are the location of the primary esophageal cancer, the length of the lesion, the presence or absence of tumor invasion and radiation dose. Most literature reports that the upper third of the esophageal cancer radiotherapy is better than the next two or three stages of esophageal cancer. The 5-year survival rate of cervical and upper thoracic esophageal cancer radiotherapy was 24.4% and 23.7%, respectively, and the middle and lower thoracic esophageal cancer were 13.7% and 5.9%, respectively. The efficacy of esophageal cancer invasion was significantly reduced. Persistent chest and back pain is an important sign of esophageal cancer invasion. The survival rate of patients without chest pain is significantly higher than those with persistent chest pain. The Shanghai Medical University Cancer Hospital reported a 5-year survival rate of 19.1% for patients without chest pain and 11.2% for patients with persistent chest pain. The longer the esophageal cancer lesions and the worse the curative effect, the Sichuan Cancer Hospital reported that the length of esophageal cancer lesions was positively correlated with invasion. Radiation dose is also an important factor affecting the efficacy. The optimal dose of radiotherapy for esophageal cancer is still inconsistent, but it is generally considered that the dose of radical radiotherapy is 60-70 Gy. It is not advisable to add blind doses. Because increasing the dose of radiation does not increase the local control rate of the lesion, it will increase the radiation damage of surrounding normal tissue.
(4) Radiation response and complications: The most common complication of radiotherapy for esophageal cancer is radiation esophagitis, and all patients have different degrees of performance. Due to improvements in radiological techniques, radiation pneumonitis and radiation-induced myelitis have rarely occurred in recent years. Other serious complications are mainly esophageal perforation, esophageal fistula and hemorrhage. In the first 1-2 weeks of radiotherapy, due to edema of the esophageal mucosa, temporary dysphagia may increase, and as the tumor retreats, the difficulty in swallowing gradually eases. After 3 to 4 weeks of radiotherapy, there may be symptoms of radiation esophagitis such as swallowing or eating pain and visceral pain. Generally, no treatment is needed, and it can be relieved by itself. A few patients can use mucosal protective agents and anti-inflammatory drugs. Sustained post-sternal pain, elevated body temperature and accelerated pulse are precursors to the esophageal orifice. Cough, especially after drinking water, is a typical manifestation of esophageal tracheal fistula. In the above situation, oral lipiodol or dilute fluoroscopy should be taken in time. Once the perforation is confirmed, the radiotherapy is stopped immediately, and corresponding treatment measures are taken, usually including fasting, gastrostomy and active rehydration support treatment.
In the past, esophageal perforation was considered to be an absolute contraindication for radiation therapy. It has been changed, and radiation therapy can be performed after the patient's condition is stable. Esophageal perforation, fistula formation and massive hemorrhage during radiotherapy are mostly caused by retraction after tumor invasion and radiotherapy, rather than excessive radiation damage. For obvious external invasion, especially for esophageal cancer with deep ulcers, the daily radiation dose should be appropriately reduced to prevent the tumor from retreating too quickly and esophageal perforation and hemorrhage.
(5) Comprehensive treatment of radiation and esophageal warming: The basis for warming and radiotherapy is that the S phase cells are resistant to radiation and sensitive to warming. Heating can increase the sensitivity to radiation. Furthermore, hypoxic cells that are resistant to radiation within the tumor are sensitive to warming. Heating can also inhibit the repair of sublethal damage and potentially fatal damage of tumor cells caused by radiation.
Hou Bingsen et al reported that the 5-year survival rate of esophageal cancer treated with heat, chemotherapy and radiation tripled was 28.2%, while radiotherapy alone was 20%. This indicates that radiotherapy, chemotherapy combined with hyperthermia can improve the local control rate of esophageal cancer. The combination of heating and radiation can also achieve synergy. Wang Jianhua et al reported that intra-abdominal warming combined with external irradiation can improve the local control rate of esophageal cancer. The short-term efficacy showed that the CR rate of the warmed combined with the external irradiation group was higher than that of the external irradiation group, and it was statistically significant. The long-term survival rate of the warming combined with the external irradiation group was higher than that of the external irradiation group. The 1-year and 3-year statistical treatments were significant, and the 5-year survival rate was 23.7%, which was higher than 16.7% of the radiotherapy alone (see Table 15). In the group with lesion length ≤ 5 cm, the warming external irradiation group was superior to the simple external irradiation group, and the 1- and 3-year survival rates were statistically significant. The 5-year survival rates of the two groups were 34% and 18%, respectively. Because of the small size of the specimen, the statistical treatment was of little significance (P>0.05) (Table 16). There was no significant difference in survival rate between 1 and 5 years in the tumor >5 cm group.
In hyperthermia combined with radiotherapy, the tumor should be warmed with sufficient heat dose, and as the temperature increases, the local control rate of the tumor will also increase. In the whole treatment process, the number of heating times has no obvious correlation with the local control rate. It is generally believed that heating once a week can be done. The key to the local control rate is the quality of each heating, that is, the temperature. In order to improve the heating quality, after each radiator is measured for the thermal dose distribution in the phantom, it should not be easily changed, and it should be regularly calibrated to ensure the heating quality.
(6) Comprehensive treatment of radiation and surgery: The treatment effect of advanced esophageal cancer is not satisfactory, and local recurrence is the main cause of treatment failure. Local recurrence after surgery, most of which is the invasion of cancer, preoperative radiotherapy can play a better therapeutic role. The local recurrence after radiotherapy is mostly the residual cancer of the original tumor. Surgical resection after radiotherapy is the most thorough treatment. Therefore, the reasonable combination of surgery and radiotherapy may be an effective method to improve the therapeutic effect of esophageal cancer.
Preoperative radiotherapy is mainly used in patients with advanced esophageal cancer, especially in clinical stage III patients with obvious external invasion. The main advantages are: 1 preoperative radiotherapy to shrink the tumor, reduce external invasion, and improve the surgical resection rate. 2 lymph node metastasis rate decreased. The 35-year survival rate has increased to varying degrees. Current data suggest that preoperative radiotherapy does not increase the difficulty of surgery, nor does it increase postoperative complications, such as postoperative infection, anastomotic leakage, etc. Radiological techniques generally use vertical and vertical radiation before and after, the irradiation field includes the whole mediastinum and the left gastric artery area, the dose is 40 ~ 50Gy / 4 ~ 5 weeks, rest after 2 ~ 4 weeks of surgery.
Postoperative radiotherapy is mainly used in the following three situations: 1 "preventive postoperative radiotherapy". For patients with "high-risk" local recurrence and regional lymph node metastasis in the advanced stage, postoperative conjunctival therapy may help to improve the cure rate. The irradiation range should include the original tumor tumor bed, anastomosis and the entire mediastinum, and the irradiation dose is 50-60 Gy/5 to 6 weeks. 2 postoperative radiotherapy for postoperative residual cancer, common sites of postoperative residual tumors include tracheal membrane, pericardium, aortic wall, anterior fascia and anastomosis, and lymph nodes remaining in the lymphatic region of the chest and left gastric artery. It is best to leave a silver clip mark around the remaining tumor and in the "high risk" area during surgery. The irradiation range is mainly based on the residual diseased area of the cancer, and is appropriately enlarged, including the surrounding lymphatic drainage area if necessary. The dose of radiation should be given to the amount of radical cure. Vertical or vertical field irradiation or oblique field irradiation is used according to different lesions. 3 postoperative recurrence or lymph node metastasis, common site local recurrence near the original tumor bed, anastomotic recurrence, mediastinal or supraclavicular lymph node metastasis. Most of these patients have late onset and have fewer chances to cure, mainly for palliative care. The irradiation range is mainly local lesions, the irradiation dose is 50-60 Gy, and the vertical irradiation is mostly used in the anterior and posterior fields.
It is not difficult to see that (Table 17) preoperative radiotherapy, chemotherapy combined with separate surgery, the three-year survival rate has increased to varying degrees, especially for patients with esophageal adenocarcinoma.
(7) Prospects for improving the efficacy of radiotherapy for esophageal cancer: For a long time, people have done a lot of research on how to improve the radiotherapy effect of esophageal cancer, including the trial of various hypoxic cell radiosensitizers combined with radiotherapy, using neutrons and negative Heavy ion irradiation such as π meson. At present, there are three main ways of making more practical significance.
1 Explore better dosage, time, and segmentation methods. The above-mentioned Haimao University Cancer Hospital and Hebei Provincial Cancer Hospital recently reported that the use of late-stage accelerated hyperfractionation method significantly improved the local control rate and survival rate, suggesting that the late-stage accelerated hyper-segmentation may be a better segmentation method.
2 Three-dimensional conformal radiotherapy technology is adopted to improve the positioning accuracy of the target area, improve the dose distribution, reduce the damage of surrounding tissues and organs, and help to improve the curative effect.
3 Explore effective comprehensive treatment options. The rational use of radiation therapy combined with surgery and chemotherapy is one of the means to improve the efficacy of esophageal cancer.
5. Other treatments
(1) Electrochemotherapy: Electrochemical therapy involves inserting a positive electrode at the center of the tumor, inserting a negative electrode around it, and then introducing a direct current to kill the cancer cells. Only in cases of advanced esophageal cancer with severe esophageal obstruction and no other effective measures, the therapy is currently in the clinical trial stage with few data.
(2) Gene therapy: Gene therapy is a therapeutic technique in which a functional gene is introduced into a cell to correct a metabolic abnormal gene or to generate a new functional gene. Tumors are caused by mutations or deletions of cellular genetic material. The ideal way to treat genes is to introduce genetic correction abnormalities, including the transfer of cell cycle genes, tumor suppressor genes, suicide genes, and inhibition of oncogene activity. Gene therapy is still in the laboratory stage, and I believe that the future may become an important means of cancer treatment.
6. Factors affecting long-term survival
(1) Clinical pathological staging: The clinical stage of esophageal cancer is determined by the symptoms, the length of the lesion seen by X-ray examination, and the presence or absence of lymph node metastasis. Therefore, its long-term postoperative efficacy is closely related to it.
(2) thoroughness of cancer resection: In addition to the surrounding tissue and local lymph nodes that should be removed from cancer, it is required to remove at least 5 to 7 cm above and below the cancer, and the anastomosis is performed at the healthy tissue. Sometimes it is impossible to achieve this requirement.
(3) Other factors include age, type of lesion, degree of differentiation of cancer, and immunity of the patient's body. In order to improve the long-term efficacy, surgical indications should be correctly mastered according to the condition and the general condition of the patient, and radical resection should be done as far as possible. Intraoperative attention should be paid to the operation technique to reduce the metastasis of cancer cells caused by surgery, pay attention to perioperative management, reduce surgical complications, and achieve good therapeutic results.
Traditional Chinese medicine treatment currently uses the combination of the main party plus syndrome differentiation, and the combination of righting and promoting blood circulation. The application of Rubescens and Rubescens in North China has been proved to have a significant cytotoxic effect on human esophageal squamous cell carcinoma CaEs-17 strain, and has a sputum effect on a variety of animal transplanted tumors. Clinical application has also proven to be effective.
(two) prognosis
There are many factors affecting the outcome of postoperative esophageal cancer. According to the literature report and the analysis of 3603 cases of thoracic surgery in the Cancer Hospital of Chinese Academy of Medical Sciences, the relevant factors are TNM staging, lymph node metastasis, degree of exacerbation of esophageal cancer, nature of resection, and incision. There are no residual cancers. The main factors affecting long-term survival are:
1. International TNM staging can more comprehensively reflect the depth and extent of cancer invasion, as well as the level of lymph node metastasis, which is the main basis for determining prognosis. The 9107 cases of surgical treatment reported in China, the 5-year survival rates of stage I, II, III, and IV were 90%, 50%, 35.8%, and 16.9%, respectively.
2. The 5-year survival rate of patients with negative lymph node metastasis was 39.3%; the positive rate was 10%. The 5-year survival rate of lymph node metastasis in cardiac cancer was 8.3% and 26.8%, respectively.
3. Invasive deep cytology census found that the 5-year survival rate of intraepithelial neoplasia after surgery is 100%, and early invasive cancer can reach more than 95%. Invasive carcinoma (intermediate and advanced cancer), the invasive muscle layer and the uninvasive muscle layer compared with the two groups, the former 5-year survival rate was 24.4%, the latter was 40.4%.
4. Malignant grading According to the three-level classification, the grade I 5-year survival rate is 38%, the grade II is 24%, and the grade III is 33%. The large-slice method was used to analyze the classification of cancer front. According to the four-level classification, the 5-year survival rate of grade I was 55.2%, the grade II was 43.3%, the grade III was 11.1%, and the grade IV was 5.9%. The difference was very significant.
5. Host resistance factors The growth of cancer is affected by host interstitial, and it is even suggested that interstitial lymphocyte infiltration is an immune phenomenon. From the perspective of cancer and host, we analyzed the peripheral lymphoid cell reaction (LCR), the fibrotic interstitial reaction of cancer, especially the thickening of the esophageal fibrous membrane, and found that the 5-year survival rate and LCR strength, between the fibers Qualitative collagenation "encirclement", whether there is thickening of esophageal fibrous membrane and the presence or absence of cancer invasion, the presence or absence and intensity of follicular germinal center hyperplasia (GH) reaction in adjacent lymph nodes are also related to 5 and 10 years survival rate. . A large number of studies have confirmed that the interstitial reaction of cancer is the morphological manifestation of host anti-cancer immunity and should be given full attention.
6. Influencing factors of long-term efficacy The esophageal recurrence cancer after the early esophageal cancer and cardiac cancer resection is the first, followed by the second organ cancer, which accounts for more than half of the total deaths. It indicates that early invasive cancer can also metastasize.
Improving early diagnosis is the primary task to improve the prognosis of esophageal cancer. Although the cytology method is still an effective early diagnosis method, it still has some pain and the rate of missed diagnosis of cardiac cancer is high. The rate has a tendency to decline year by year. In recent years, new non-invasive detection technologies have emerged, such as ultra-micro gastric juice series screening method, electronic acupoint detection method, and swallowing sound map microcomputer diagnostic instrument, etc., all of which are fast, simple and painless screening methods. The rate is about 90%, which helps to make up for the shortage of pulling nets.
prevention:
Prevention of esophageal cancer is undoubtedly the most fundamental measure to control esophageal cancer. According to the multi-stage development of esophageal cancer, that is, the initiation, promotion and evolution stages, from the perspective of etiology, pathogenesis and clinical medicine, prevention of esophageal cancer The occurrence and development are divided into three levels of prevention.
1. Primary prevention primary prevention, ie etiology prevention, is the fundamental way to reduce the incidence of esophageal cancer. It is closely related to the progress of epidemiological research and etiology research. This is the most ideal method, but it is very difficult. It is still difficult to carry out in full.
(1) Changing the habit of eating mildew food: There is sufficient evidence to show that the consumption of mildew food, especially sauerkraut, moldworm and fish sauce, is one of the important factors in the pathogenesis of esophageal cancer. Therefore, it is necessary to vigorously promote such food pairs. The harm of human health makes the people eat less or not, and encourages the cultivation of vegetables and fruits to increase the intake of fresh vegetables and fruits and to supplement vitamin C. Mildew foods, on the one hand, produce mycotoxins or metabolites, on the one hand promote the internal synthesis of nitrosamines, which is the main cause of esophageal cancer. Eating more fresh vegetables or supplementing vitamin C can block the synthesis of nitrosamines in the body. It can reduce the content of nitrosamines in the stomach, thereby reducing the exposure level of nitrosamines in the stomach. In addition, Lin County's nutritional prevention test found that supplementation of riboflavin and niacin can reduce the incidence of esophageal cancer by 15%. At the same time, we should actively study scientific methods for making and preserving sauerkraut to meet the traditional eating habits that have been developed by local residents since generations.
Change bad eating habits, don't eat moldy food, eat less or not eat sauerkraut. Improve water quality and reduce nitrite content in drinking water. Promote trace element fertilizers and correct the trace elements such as molybdenum deficiency in soil. The application of Chinese and Western medicine and vitamin B2 in the treatment of esophageal epithelial hyperplasia to block the process of cancer. Active treatment of esophagitis, esophageal leukoplakia, achalasia, esophageal diverticulum and other diseases associated with esophageal cancer. Susceptible people to monitor, popularize anti-cancer knowledge and improve anti-cancer awareness.
(2) Anti-mildew of grain: Mild grain food contains a variety of carcinogenic toxins, so it is very important to actively carry out anti-mildew and detoxification work of food, especially the importance of anti-mildew for household grain storage. Generally, the water content of grain is below 13% to meet the requirements of mildew proof. Once the grain has been mildewed, it should be taken after diligence, picking when eating, washing twice and adding alkali, which can effectively reduce the intake of mycotoxins.
(3) Strengthening the sanitation management of drinking water: It has been found that the content of nitrosamines in water in high-incidence areas of esophageal cancer is significantly higher than that in low-incidence areas. Therefore, it is very important to do a good job in environmental sanitation and prevent water pollution. Gradually reduce the area where drinking pond water is used and promote soil tap water. The bleached powder disinfection should also be carried out on the ditch pond water, which can significantly reduce the nitrosamine content in water and kill other infectious diseases.
(4) Prevention of genetic pathogenic factors: Esophageal cancer has a relatively common family aggregation phenomenon, indicating that the cancer susceptibility of family history of esophageal cancer does exist, and the monitoring work of the same generation should be strengthened. When the patient is a male, the male monitoring is strengthened, especially in the group before the age of 49. The patient is a female, and the female monitoring is strengthened, especially in the 50-69 year old population, and 2 or more esophagus should occur in 3 generations. A family that has died of cancer is considered a dangerous family. Members of these families who are 40 to 69 years old are considered as risk groups. Regular medical examinations, provision of preventive drugs or vitamins, and persuasion to change lifestyle habits are positive for reducing the incidence of esophageal cancer. significance.
2. Secondary prevention For esophageal cancer, it is impossible to completely achieve primary prevention at present. Due to the long-term occurrence and development of esophageal cancer, it is a realistic and feasible method for tumor prevention if early detection, early diagnosis and timely treatment, especially the prevention of the development of precancerous lesions.
(1) Census: The high-incidence area is over 35 years old, family history of esophageal cancer, or patients with esophageal epithelial hyperplasia are classified as high-risk groups, and key monitoring is carried out, and residents over 35 years old in areas with high incidence of esophageal cancer should be investigated as much as possible. The census is mainly based on esophageal cytology. When suspicious patients are found, endoscopy should be performed as soon as possible to achieve early diagnosis. The early manifestations of esophageal cancer, such as "swallowing discomfort" should be well known to the general population in high-incidence areas, and the patient's visit time can be advanced for early diagnosis and treatment.
(2) Drug prevention of precancerous lesions: precancerous lesions of esophageal cancer mainly refer to severe hyperplasia of the esophageal epithelium, with anti-cancer B III tablets (Soybean root, Sabina, white sable, yellow medicinal, Prunella, Caohe) Six kinds of anti-cancer tablets consisting of six herbs were added with 2mg 5-fluorouracil, anti-cancer tablets and Tailuolong for severe hyperplasia of esophageal epithelium. The cancer rate of untreated group was 7.4%. The cancer rate of treatment group: anti-cancer B group 2.5%, 1.4% in the anti-cancer group and 2.3% in the tyloron group, which were significantly different from the untreated group and more normal than the untreated group.
Since 1983, the Chinese Academy of Sciences has conducted a study on the treatment of esophageal precancerous lesions in Heshun Township, Lin County, Henan Province, and Leikou Township, Anyang County. Through esophageal cytology screening, 2,531 patients with esophageal epithelial recurrence were randomly divided into three groups, taking anti-cancer tablets, retinoic esters and placebo. A total of 3393 people were detected and randomly divided into two groups, taking riboflavin and placebo. In 3 and 5 years, the patient's medication rate was over 90%. After 3 and 5 years of medication, esophageal cytology was reviewed. The results were confirmed. Anti-cancer B tablets reduced the cancer rate of esophageal re-increase by 52.2%, reaching the target. Valetamine and riboflavin also showed a certain blocking effect, which reduced the cancer rate of esophageal re-increase and mild increase by 37.3% and 22.2%, respectively, and found that increasing the dose of retinoic ester can significantly improve its prevention. Cancer effect. After 5 years of taking riboflavin, the cancer rate of esophageal deliberation decreased by 34.8%, which was 22.2% lower than that of 3 years after taking the drug, which increased by 56.8%, indicating that the longer the riboflavin is taken, the inhibition of mild carcinogenesis. The more obvious. The anti-cancer tablets used in the experiment are made of six traditional Chinese medicines, which are unique in China and low in price and easy to promote. Retinoids are currently the most adequate and promising class of cancer preventives. The retinoic ester has a strong action, low toxicity and good preventive effect. Riboflavin is an essential vitamin for the human body. If it can further confirm its anti-cancer effect, it has far-reaching significance.
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