I. Epidemiology of gastric cancer and risk factors for its occurrence
Before 1930, gastric cancer was the first cause of death among all cancers in most countries in the world. The prevalence of gastric cancer began to decline after the 1930s, associated with the widespread use of refrigerators, which led to a shift in the method of food preservation from salt curing to refrigeration.
In 2008, there were 990,000 new cases of stomach cancer (7.8% of all cancers) and 738,000 deaths worldwide. China is a country with high incidence of gastric cancer, with about 400,000 new cases each year. According to the statistics in 2013, the incidence of gastric cancer in men and women is the 2nd and 4th of all malignant tumors, respectively, and the trend of new patients is younger.
Nitroso compounds are the first carcinogens that are considered to be closely related to the occurrence of gastric cancer. H. pylori infection is associated with the occurrence of gastric cancer and has been listed as a class 1 carcinogen for human gastric cancer in the 1994 yearbook of the WHO International Agency for Research on Cancer.
The risk factors for gastric cancer include male, first-degree relatives with gastric cancer, age 40-45 years or older, abnormal pepsinogen status, long-term H. pylori infection, etc.; smoking, excessive consumption of preserved, smoked or excessive salt foods, excessive consumption of red meat and less vegetables, and obesity are all possible risk factors.
Pre-cancerous changes in the stomach
Lauren`s staging, which was proposed in 1951 and perfected in 1965, broadly classifies gastric cancer into intestinal gastric cancer and diffuse gastric cancer according to the origin of the tumor. For the more common intestinal gastric cancer, the famous Correa theory is still used so far, which considers precancerous state (i.e. precancerous diseases such as chronic atrophic gastritis) and precancerous lesions (mainly refers to heterogeneous hyperplasia, i.e. intraepithelial neoplasia) as precancerous changes of gastric cancer. Nowadays, Western scholars often regard chronic atrophic gastritis (with or without intestinal epithelial hyperplasia) as precancerous lesions of the stomach in a broad sense.
The clinical significance of intestinal epithelial metaplasia typing has also undergone ups and downs, with incomplete colorectal type of intestinal epithelial metaplasia being considered more likely to be carcinogenic, but later found to be less clinically significant than the range of intestinal epithelial metaplasia; and the Meta-analysis by the Correa group showed that most clinical evidence supports the value of intestinal epithelial metaplasia typing in predicting the risk of gastric cancer.
III. Screening and follow-up
In Japan, barium meal or serum pepsinogen I and II tests have been used as primary screening, followed by endoscopy since the 1970s. Although both Japan and Korea are gradually using more endoscopy as a screening tool, the cost issue still plagues staff and local governments. Other markers that can be used for screening or early warning and early diagnosis are listed in Table 1. In recent years, studies have shown that more microRNAs can be detected in blood, stool, or tissue specimens for screening and prognosis, but they are not yet mature.
IV. Diagnosis
As early as 100 years ago, the main diagnosis of gastric cancer before surgery was bismuth x-ray imaging. In 1923, British physicians began to determine whether there was impaired gastric emptying by measuring the concentration of acid in gastric juice and having patients eat milk containing charcoal to help diagnose early gastric cancer. In the 1940s, the barium meal test began to mature, and the experience gained enabled the imagers to understand how to achieve a better examination by changing the body position.
At the same time, cytological examination of gastric fluid began to be attempted. After the invention of gastroscopy in Japan in 1950, the use of endoscopy for gastric cancer diagnosis began to develop gradually. Today, in addition to white light endoscopy, pigmented endoscopy and other endoscopes have emerged. The application of confocal microscopic endoscopy has important clinical value, but unfortunately it is not yet widespread in the current state, and relatively narrow-band imaging magnification endoscopy is more widely used.
In 2005, the International Atrophy Study Group proposed the following staging criteria for the degree of inflammatory response and atrophy of the gastric mucosa different from the New Sydney Gastritis System, which has since been summarized by the international working group as the OLGA Graded Staging Assessment System. Applying this system, stage III and IV atrophic gastritis requires endoscopic and pathologic follow-up.
For pathologic diagnosis, the new 2010 edition of WHO gastric cancer staging classifies gastric cancer into 6 types, including adenocarcinoma, adenosquamous carcinoma, medullary carcinoma, hepatocellular carcinoma, squamous cell carcinoma, and undifferentiated carcinoma.
V. Prevention
It should be said that the prevention of gastric cancer has been really emphasized in the past 40 years. Endoscopic resection of heavy precancerous mucosa is an effective means to prevent gastric cancer. The other easier means of prevention remains the eradication of H. pylori, especially in areas with a high incidence of gastric cancer. Recent studies have demonstrated the long-term preventive effect of H. pylori eradication. Epoxygenase 2 inhibitors are also a potentially effective chemopreventive agent, but their use is limited by their potential to cause adverse effects of cardiovascular events. However, studies have shown that eradication of H. pylori in combination with cyclooxygenase 2 inhibitors does not enhance the prophylactic effect.
The preventive effect of vitamins has been debated for decades, but there are more positive views. Some literature suggests that the application of allicin preparations and multivitamins has a long term preventive effect.
VI. Combination therapy
The National Comprehensive Cancer Network (NCCN) publishes various clinical practice guidelines for malignant tumors every year, and scholars in China have published the Chinese version of the NCCN clinical guidelines for the diagnosis and treatment of gastric cancer with reference to translation; in addition, the Consensus Opinions on Chronic Gastritis in China (2012, Shanghai) and the Consensus Opinions on Early Gastric Cancer Screening and Endoscopy in China (2012, Shanghai) have been published. In addition, the Chinese Consensus Opinion on Chronic Gastritis (2012, Shanghai) and the Chinese Consensus Opinion on Early Gastric Cancer Screening and Endoscopic Diagnosis and Treatment (2014, Changsha) have also guided the clinical work to some extent. Nowadays, multidisciplinary team (MDIF) model is mostly adopted for treatment according to tumor pathological type and clinical stage, combined with patients’ general status and organ function status.
1.Endoscopic treatment.
The concept of early gastric cancer was first proposed by Japanese scholars in 1962. For early gastric cancer without evidence of lymph node metastasis, endoscopic treatment or surgery is considered depending on the depth of tumor invasion. Compared with conventional surgery, endoscopic treatment is not only comparable in efficacy, but also less invasive, less complications and relatively inexpensive. Therefore, it is recommended as the treatment of choice for early gastric cancer. It mainly includes endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD).
Endoscopic treatment of polyp-like neoplasms first began in 1968, while endoscopic mucosal resection and dissection began to be attempted by Japanese scholars after 1983. Until 1999, the invention of the IT knife made ESD commonplace, and ESD has higher rates of whole and complete resection than EMR, and lower rates of local recurrence, but higher rates of complications such as perforation. Recently, endoscopists have tried to perform endoscopic resection of early gastric cancer with a robotic arm, one of which separates the mucosa and the other removes it, which has some application prospects.
2.Surgical treatment.
Based on Billroth’s gastrectomy in 1881 and Roux’s total gastrectomy in 1908, surgical methods have been continuously improved. At present, the commonly used surgical methods include reduction surgery, stereotyped gastrectomy and enlargement surgery, and the contouring of D2 lymph nodes is regarded as the surgical standard for gastric cancer.
3.Radiation therapy.
Radiation therapy for gastric cancer started in 1896, initially treated with X-rays, but the efficacy was poor due to the large number of surrounding organs, which would be damaged by high doses of radiation, while the tumor was insensitive to small doses. Recent Meta-analyses have shown that patients can benefit from both preoperative neoadjuvant radiation therapy and postoperative adjuvant radiation therapy when combined with chemotherapy. Our guidelines recommend the use of CT simulation to identify high-risk recurrence areas of the primary tumor and lymph node areas as targets for radiation therapy.
4.Chemotherapy.
Chemotherapy regimens based on mitomycin C, 5-fluorouracil and adriamycin were popular in the 1970s, and etoposide and cisplatin (CDDP) regimens were introduced in 1987. centered regimens.
A 2010 Meta-analysis by the GASTRIC Study Group (Global Advanced/Adjuvant Stomach Tumor Research International Collaboration) showed that adjuvant chemotherapy significantly improved disease-free survival and overall survival (HR=0.82), with a 5-year survival increase of approximately 50 percent. The 5-year survival rate was increased by approximately 50%, and chemotherapy regimens that included fluorouracil significantly reduced the rate of death. Current chemotherapy can be divided into palliative, adjuvant and neoadjuvant chemotherapy.
5.Biological therapy.
It is a new treatment method for gastric cancer, which mainly includes the use of non-specific immune enhancers, cytokine therapy and molecular targeted therapy. Non-specific immune enhancer therapy is less suppressive to immune function, and the representative drugs include BCG (bacillus calmette-Guerin, BCG) and Su strain of Streptococcus lyophilized powder (OK-432). Cytokine therapy includes IL-2, IFN, TNF, colony-stimulating factor, and lymphokine-activated killer cells (LAK cells).
Molecular targeted therapy is the most popular treatment today. This therapy couples monoclonal antibodies with chemotherapeutic drugs, and uses the special affinity of antibodies for cancer cells to target and kill cancer cells, which is suitable for removing subclinical lesions or small residual lesions after surgery, and reducing recurrence and metastasis of gastric cancer. The main methods include.
① Targeted therapy against epidermal growth factor receptor (EGFR), the most common ones are anti-EGFR monoclonal antibodies, including cetuximab monoclonal antibody and pani monoclonal antibody. EGFR inhibitors, such as gefitinib, are also available.
(ii) 7-34% of gastric cancers are human epidermal groWth factor receptor2 (HER2) positive, and monoclonal antibody therapy against them is often effective, the most representative one being trastuzumab, which has been proven in phase III clinical trials to significantly improve median survival.
The most representative monoclonal antibody is trastuzumab, which has been proven to improve the median survival of patients in phase III clinical trials. ③ Targeted therapy against tumor neoangiogenesis, including the vascular endothelial growth factor family and its receptors, includes bevacizumab monoclonal antibody, ramolute monoclonal antibody, and some drugs that inhibit tumor angiogenesis, such as sunitinib, sorafenib and apatinib.
In conclusion, the clinical diagnosis and treatment status of gastric cancer has changed tremendously and progressed rapidly in recent years. Although it is far from solving the aim of curing and completely preventing gastric cancer, it has pointed out the direction for future research.