[Literature Sharing] Progress in prevention, diagnosis and treatment of early gastric cancer
In 2020, the number of new cases of gastric cancer in the world exceeded 1 million, ranking the top five in the global cancer incidence rate, with 768,000 deaths and the fourth mortality rate. By 2040, there are expected to be 1.77 million new cases and 1.27 million deaths worldwide. Asia have the highest incidence and death rates globally, with nearly 820,000 new cases and 576,000 deaths in 2020. More than 90% of gastric cancer cases are sporadic, about 10% present as familial clusters, and 1-3% of cases result from inherited cancer syndromes.
The prevention of gastric cancer is a key public health challenge, the early diagnosis of lesions is essential to provide definitive minimally invasive treatment and improve survival rates. Published by Clara Benedetta Conti et al., of the Interventional Endoscopy Foundation, SAN Gerardo de Tintori, Italy, in the International Journal of Environmental Research and Public Health. The article "Early Gastric Cancer: Update on Prevention, Diagnosis and Treatment" provides a review on the prevention, diagnosis and treatment strategies of early gastric cancer.
1. Prevention
The main known risk factors for gastric cancer are H. pylori infection, smoking, high intake of processed meats, obesity, and alcohol consumption. While some factors such as citrus fruits and polyphenol intake, non-steroidal anti-inflammatory drugs (NSAIDs), statins, metformin and aspirin may have a protective effect.
1.1 Risk Factors
1) Helicobacter pylori (Hp)
Helicobacter pylori (Hp) is classified as a Class 1 carcinogen and a major environmental risk factor for gastric cancer. Infection with Hp increases the risk of developing gastric cancer by 1.4 to 4.2 times, and eradication of all Hp infections would prevent approximately 89%, 29%, and 74% of NCGC, CGC, and gastric non-Hodgkin's lymphomas, respectively.
2) Smoking
Smoking is classified as a class 1 carcinogen in GC, with data suggesting that smokers have a 25% increased risk of developing gastric cancer, and is strongly associated with the intensity and duration of smoking. Compared with never smokers, smoking more than 20 cigarettes per day is associated with a 32% increased risk and smoking for more than 40 years is associated with a 33% increased risk. The probability of developing GC about 10 years after quitting was similar to that of non-smokers.
3) Alcohol drinking
Alcohol drinking is associated with an increased risk of gastric cancer, and in Deng et 's meta-analysis, drinkers had a significantly higher risk of GC than non-drinkers, with an odds ratio (OR) of 1.20. Heavy drinkers had an OR of 1.30.
4) Processed Meats
Processed meats (smoked and cured) are often defined as general carcinogens, and consumption of red and processed meats was associated with an increased risk of gastric cancer at 41% and 57%, respectively.
5) Obesity
In recent years, obesity has been identified as a related risk factor for the development of many types of cancer and is likely to surpass the role of smoking in the next few years. Yang et al. 's meta-analysis confirmed that BMI is linearly correlated with GC risk, and obesity may increase the incidence of gastroesophageal reflux, which ultimately leads to esophageal adenocarcinoma and cardiac GC. In addition, insulin resistance may also play a carcinogenic role.
1.2 Protective Factors
1) Citrus fruits and polyphenols
Vegetables and fruits are often associated with a reduced risk of many tumors and gastric cancer. There is some evidence that the protective effects of citrus fruits may be related to the presence of bioactive compounds like vitamin C, flavonoids. Polyphenols are found in a variety of vegetables, fruits, grains, dried legumes, and spices. In a large pooled analysis, high intakes of total and specific polyphenols were found to be inversely associated with GC risk, and some of them can even inhibit the growth of Hp, have antibacterial properties, and can also trigger apoptosis in cancer cells.
2) NSAIDs, aspirin, statins, and metformin
Nsaids have been studied as potential protective factors for gastric cancer. A meta-analysis has shown that NSAIDs, aspirin, and non-aspirin NSaids reduce GC risk, but the protective mechanisms are unclear and controversial.
2. Screening
A screening test is a form of secondary prevention that detects early cancer and precancerous lesions in asymptomatic patients. Ideally, a screening test for gastric cancer will reduce mortality and improve treatment success by removing early gastric cancer and precancerous lesions. In addition, given the availability of serum markers, imaging tests, and especially endoscopy, clinicians should be encouraged to screen patients at high risk for gastric cancer.
2.1 Precancerous lesions
The gastric cancer cascade proposed by Correa, namely chronic superficial gastritis--chronic atrophic gastritis--intestinal metaplasia--dysplasia--gastric cancer, is currently the widely recognized main mode of intestinal gastric cancer formation. During endoscopy, doctors should look for precancerous and visible lesions to ensure proper monitoring and treatment.
2.2 Screening tests for early gastric cancer
Ideally, screening tests for cancer should be able to identify high-risk people and early lesions. This can help avoid the use of endoscopes to diagnose EGC at an early stage. In populations with lower cancer-adjusted mortality rates, such as in Western countries, the development of non-invasive tests to stratified the risk of gastric cancer and to offer endoscopic screening according to risk categories should be promoted even more.
1) Serological Markers
Traditional GC markers such as CEA, CA19-9, CA12-5, CA72-4 have low sensitivity and specificity for GC detection, and have little effect on the early diagnosis of GC. Serum pepsinogen (PG) is one of the most studied biomarkers for screening gastric cancer at present. Pepsinogen I (PGI) is secreted by the basal glands, while pepsinogen II (PGII) is secreted by the basal glands, pyloric cells, and Brunner's glands.
Serum PGI and PGII levels increase with the progression of gastritis. Serum PGI levels gradually decrease due to the reduction of basal glandular mucous membranes caused by gastritis, while serum PGII levels remain stable. Therefore, the serum PGI/PGII ratio (PGR) decreases with the progression of gastritis, reflecting the severity of stomach atrophy.
Another biomarker associated with atrophic gastritis is gastrin-17 (G-17), which is secreted by G endocrine cells and depends on stomach acid. One serological assay, which included PGI, PGII, G-17 and Hp, had a sensitivity of 39.9% and specificity of 93.4% for predicting atrophic gastritis.
Novel molecular biomarkers associated with DNA and RNA are also being used for early tumor detection. The most studied epigenetic alterations are abnormal DNA methylation, histone modifications, and dysregulated expression of non-coding Rnas (including long non-coding Rnas (lncRNAs) and microRNAs (miRNAs)).
2) Imaging
Since 1960, Japan began to use fluorescent prime minister technology to screen for gastric cancer, which has significantly reduced the mortality rate of gastric cancer by 40-60%. The abnormal manifestations may be gastric strictures, strictures, malformations, stiffness, barium cisternization, irregular gastric region, altered gastric folds, or polypoid lesions. But all radiographic abnormalities must be confirmed by endoscopy.
3) Endoscopy
Japan and South Korea are the first countries to implement mass population GC screening. Current guidelines in Japan and South Korea recommend endoscopic screening every two years for gastric cancer in asymptomatic adults aged 50-75 and 40-75, respectively, and do not recommend GC screening in adults older than 85 years.
Endoscopy is the gold standard for GC and EGC diagnosis, and the implementation of technologies such as digital CE has the potential to further improve the detection rate of EGC. In a population-based study that evaluated the impact of switching from radiography to endoscope-based GC mass screening, a significant reduction in GC-related mortality was found (5.0/ year vs 2.1/ year). As a result, the use of endoscopy-based testing has outpaced imaging screening in Asian countries over the past decade.
Limiting the widespread use of endoscopic screening is mainly the risk of over-diagnosis, potential complications, endoscopist level, and endoscopic resources.
3. Treatment
3.1 Endoscopic Resection (ER)
In general, the indication for endoscopic resection (ER) is determined by the risk of lymph node metastasis (LNM) and the likelihood of achieving a holistic resection. Basically, the recommended endoscopic treatments for EGC lesions are endoscopic mucosal excision (EMR) and endoscopic mucosal dissection (ESD). Factors that guide the physician in selecting the most appropriate endoscopic treatment are the type of histopathology, the size of the lesion, the depth of infiltration, and the presence of ulcers.
3.2 Surgical Procedures
When ER is not feasible and the lesion does not meet ER criteria, the patient needs to be directed for surgical treatment. New minimally invasive approaches and personalized treatment options may provide a favorable long-term tumor prognosis and good quality of life for patients with early gastric cancer.
3.3 Comparison of endoscopic resection and surgery
Some studies have shown that patients treated with ESD have shorter hospital stays and surgery, and fewer adverse events such as bleeding, stomach problems, and perforation(p = 0.001). In addition, there was no statistical difference in 5-year overall survival and 5-year relapse-free survival between the two groups (surgery and ESD) : 5-year overall survival was 96.1% and 91.4% (p = 0.08) in the surgery and ESD groups, and 95.8% and 91.4%, respectively.
4. Summary
Gastric cancer remains a serious public health problem worldwide due to its high and growing mortality rate, and prevention is key to reducing mortality.
1) Firstly, more emphasis should be placed on lifestyle changes to reduce risk factors.
2) Secondly, where possible, Helicobacter pylori eradication treatment should be encouraged.
3) Thirdly, for patients at higher risk for gastric cancer, existing screening tests such as serological markers or endoscopy may be considered. 4) Monitoring of precancerous lesions and endoscopy can improve the prevention and detection of early gastric cancer.
But the lack of systematic gastric cancer screening tests worldwide remains a major obstacle to detecting early stage lesions. Therefore, screening for early gastric cancer and precancerous lesions should be encouraged and widely implemented in large populations as much as possible.
