Gastric cancer ranks first among all kinds of malignant tumors in China, with the age of prevalence above 50 years old and the ratio of male to female incidence is 2:1.
1.Etiology
The exact cause of gastric cancer is not very clear, but the following factors are related to its development.
1.1 Geographical environment and dietary and living factors have obvious geographical differences in the incidence of gastric cancer, and the incidence rate of gastric cancer in northwest and eastern coastal areas of China is significantly higher than that in southern areas.
The high incidence of distal gastric cancer in people who consume smoked and salted foods for a long time is related to the high content of carcinogens or former carcinogens such as nitrite, fungal toxins and polycyclic aromatic hydrocarbon compounds in foods; the lack of fresh vegetables and fruits in food is also related to the incidence. The risk of gastric cancer in smokers is 50% higher than that in nonsmokers.
1.2 Helicobacter pylori (HP) infection HP infection is also one of the main factors triggering gastric cancer. The prevalence of HP infection in adults in high incidence areas of gastric cancer in China is over 60%, which is higher than that in low incidence areas (13%~30%).
HP infection causes chronic inflammation of gastric mucosa plus environmental pathogenic factors that accelerate the overproliferation of mucosal epithelial cells, leading to aberration and cancer; the toxic products of H. pylori, CagA and VacA, may have cancer-promoting effects, and the detection rate of anti-CagA antibody in gastric cancer patients is significantly higher than that of the general population.
1.3 Precancerous lesions are benign gastric diseases and pathological changes that increase the risk of developing gastric cancer.
Gastric diseases that are prone to gastric cancer include gastric polyps, chronic atrophic gastritis and residual stomach after partial gastrectomy. These lesions may be accompanied by chronic inflammatory process of different degrees, intestinal epithelial hyperplasia or atypical hyperplasia of gastric mucosa, which may be transformed into cancer in a long time.
Gastric polyps can be divided into inflammatory polyps, hyperplastic polyps and adenomas, the first two of which have little possibility of malignant transformation, while the cancer rate of gastric adenomas is about 10%-20%, and the chance of cancer increases when the diameter exceeds 2 cm.
1.4 Genetic and genetic genetic and molecular biology studies have shown that the incidence of gastric cancer is four times higher in blood relatives of gastric cancer patients than in the control group.
There is much evidence that gastric carcinogenesis is associated with loss of heterozygosity and mutations in the oncogenes P53, APC, and DCC. Molecular biology studies have shown that oncogenes c-met and K-ras are significantly amplified and overexpressed in gastric cancer tissues; and the invasiveness and metastasis of gastric cancer are closely related to the abnormal expression of CD44υ gene.
2.Clinico-pathological staging
The TNM staging method of gastric cancer published by the International Union Against Cancer in 1987 is based on the depth of tumor infiltration, lymph nodes and distant metastasis.
T1: tumor infiltrates into mucosa or submucosa; T2: tumor infiltrates into muscle layer or subplasma layer; T3: tumor penetrates into plasma layer; T4: tumor directly invades adjacent structures or organs, such as invading esophagus, pancreas, etc.
N0: no lymph node metastasis; N1: lymph node metastasis within 3 cm from the edge of the primary focus; N2: lymph node metastasis beyond 3 cm from the edge of the primary focus.
M0: no distant metastasis; M1: distant metastasis.
Table 1 Intermediate stage IV gastric cancer includes the following conditions: N3 lymph node metastasis, liver metastasis (H1), peritoneal metastasis (P1), positive abdominal exfoliative cell examination (CY1) and other distant metastasis (M1).
If the primary tumor is confined to the mucosal layer without invading the intrinsic layer of mucosa, it is considered as carcinoma in situ, which is indicated by Tis, and when the tumor is TisN0M0, it is considered as carcinoma in situ, also called stage 0.
Due to the advancement of diagnostic technology, it is possible to make a judgment on tumor infiltration and metastasis before surgery and perform clinical staging, which is indicated by CTNM. The postoperative pathological staging is expressed as PTNM.
3.Diagnosis
It is no longer difficult to diagnose gastric cancer through barium X-ray and fiberoptic gastroscopy plus biopsy. Due to the lack of specific symptoms of early gastric cancer, low consultation rate of patients, and the lack of effective and convenient screening means, early gastric cancer accounts for less than 10% of gastric cancer inpatients in China at present.
In order to improve the diagnosis rate of early gastric cancer, people with a family history of gastric cancer or a history of pre-existing gastric disease should be examined regularly. Those who have upper gastrointestinal symptoms without biliary tract disease over 40 years old; those who have chronic blood loss in the gastrointestinal tract with unknown reasons; those who have significant weight loss and loss of appetite in a short period of time should have stomach-related examinations to prevent missing the diagnosis of gastric cancer. At present, the following four kinds of tests are mainly used to diagnose gastric cancer in clinical practice.
3.1 Barium meal X-ray examination Digital X-ray gastrointestinal imaging technology has greatly improved the resolution and clarity of images, and is still a common method to diagnose gastric cancer. The diagnosis is often made through the observation of mucosal phase and filling phase by using dual gas-barium imaging. The main change of early gastric cancer is the abnormal mucosal phase, and the morphology of progressive gastric cancer is basically the same as the general typing of gastric cancer.
3.2 Fiberoptic gastroscopy is the most effective method to diagnose gastric cancer because it can directly observe the location and scope of gastric mucosal lesions and obtain lesion tissues for pathological examination, and in order to improve the diagnosis rate, no less than 4 biopsies of suspicious lesions should be performed.
Endoscopic Congo red and US blue biopsy staining techniques can significantly improve the detection rate of small gastric cancer and micro gastric cancer. The use of fiberoptic gastroscope with ultrasound probe for ultrasound detection and imaging of the lesion area can help to understand the depth of tumor infiltration and whether there is invasion and metastasis of surrounding organs and lymph nodes.
3.3 Abdominal ultrasound is mainly used to observe the infiltration and lymph node metastasis of the adjacent organs of stomach (especially liver and pancreas) in the diagnosis of gastric cancer.
3.4 Spiral CT with positron emission imaging Multi-row spiral CT scan combined with 3D stereoscopic reconstruction and simulated endoscopic technology is a new non-invasive examination tool, which is helpful for the diagnosis and preoperative clinical staging of gastric cancer. Using the affinity of gastric cancer tissue for fluoro-2-deoxy-D-glucose (FDG), positron emission tomography (PET) can determine the lymph nodes and distant metastases with high accuracy.
4.Treatment
4.1 Drug therapy As drug therapy and chemotherapy for gastric cancer gradually become the main treatment means, they are mainly used before, during and after radical surgery to prolong survival. The use of appropriate amount of chemotherapy for patients with advanced gastric cancer can slow down the development of tumor, improve symptoms and have certain recent effects.
4.1.1 Indications
In principle, adjuvant chemotherapy is not necessary after radical surgery for early gastric cancer. Adjuvant chemotherapy should be administered to patients with the following conditions: high malignancy of pathological type; cancer lesion area >5 cm2; multiple cancer lesions; age <40 years.
Those with progressive gastric cancer after radical surgery, palliative surgery, or recurrence after radical surgery need chemotherapy. Patients with gastric cancer should have a clear pathological diagnosis, good general condition, normal heart, liver, kidney and hematopoietic functions, and no serious comorbidities for chemotherapy.
4.1.2 Drug delivery method
The commonly used routes of administration of chemotherapy for gastric cancer include oral administration, intravenous and peritoneal administration, and regional perfusion administration by arterial cannulation.
Commonly used oral chemotherapeutic drugs include tegafur, eflornithine, fluorotiron, etc. Commonly used intravenous chemotherapeutic agents include fluorouracil, mitomycin, cisplatin, adriamycin, etoposide, calcium formyl tetrahydrofolate, etc.
(1) Tegafur is a precursor drug that is first metabolized to 5-fluorouracil in the liver, and the active product of 5-fluorouracil conversion forms a complex with thymidylate synthase and 5,10-methylenetetrahydrofolate encoded by the 7YMS gene, which hinders the synthesis of DNA and RNA.
Currently, tegafur is mainly used for the treatment of gastric and colorectal cancers. Compared with 5-fluorouracil, a clinically important anti-cancer drug, tegafur is well absorbed, safe and effective, with less toxic side effects.
(2)Euphradine is a compound preparation of tegafur and uracil (1:4), which gradually transforms into fluorouracil in the body, and plays the role of interfering and blocking DNA, RNA and protein synthesis.
(3) Fluorotiron is a precursor drug of 5-fluorouracil. Its structure is similar to that of thymine nucleoside and uracil nucleoside, and fluorotiron is converted to 5-fluorouracil under the action of PyNPase to exert anti-tumor effects.
(4) Fluorouracil is a derivative of uracil in which the hydrogen at the 5th position is replaced by fluorine, which is converted into 5-fluorouracil deoxyribonucleotide in cells and inhibits deoxythymidine synthetase, preventing the conversion of deoxyuridine methylation into deoxythymidine and thus inhibiting DNA synthesis.
In addition, fluorouracil can be converted to 5-fluorouracil nucleoside in vivo, which is incorporated into RNA as a pseudo-metabolite to interfere with protein synthesis, and therefore has effects on other cells in various stages.
Fluorouracil is irregularly absorbed orally and needs to be administered intravenously. After absorption, it is distributed in body fluids, with high concentration in liver and tumor tissues.
(5) Mitomycin has an alkylating effect due to the presence of ethylenimine and carbamoyl ester groups in its chemical structure. It can cross-link with the double strand of DNA, inhibit DNA replication, and can also make part of the DNA strand break, which is a non-specific drug of cell cycle.
(6) Cisplatin is a metal complex with a chlorine atom and two amino groups. After entering the body, it first dissociates the chlorine contained and then forms cross-links with the bases on the DNA strand, thus destroying the structure and function of DNA, which is a cell cycle specific drug.
(7) Adriamycin is an anthracycline antibiotic, which can be embedded between DNA base pairs and tightly bound to DNA, preventing rRNA synthesis and DNA replication, and is a cell cycle specific drug.
(8) Etoposide is a cell cycle specific antitumor drug, its mechanism of action is mainly to inhibit DNA topoisomerase II, thus interfering with DNA structure and function, but its adverse effects (bone marrow inhibition, gastrointestinal reactions, etc.) are more and more serious, limiting the clinical application of the drug.
(9) Calcium formyltetrahydrofolate is an important coenzyme for nucleic acid synthesis. When combined with 5-fluorouracil, exogenous calcium formyltetrahydrofolate can make the triplet complex bind firmly and enhance the inhibition of thymidylate synthase, thus increasing the antitumor effect of calcium formyltetrahydrofolate.
In order to improve the effect of chemotherapy and reduce the toxic side effects of chemotherapy, multiple chemotherapeutic agents are often used in combination. The more commonly used chemotherapy regimens in clinical practice are.
(1) FAM regimen: Fluorouracil 600 mg/m2 intravenous drip, dosing in the 1st, 2nd, 5th and 6th weeks; Adriamycin 30 mg/m2, intravenous push, dosing in the 1st and 5th weeks; mitomycin 10 mg/m2, intravenous push, dosing in the 1st week. 6 weeks is a course of treatment.
(2) MF regimen: mitomycin 8-10 mg/m2, intravenous injection, on the first day; 5-fluorouracil 500-700 mg/m2 daily, intravenous drip, for 5 d. 1 month as a course of treatment.
(3) ELP regimen: calcium folic acid 200 mg/m2, ___ first intravenous injection, day 1~3; 5-fluorouracil 500 mg/m2 intravenous drip, day 1~3; etoposide 120 mg/m2 intravenous drip, day 1~3. Every 3~4 weeks is a course of treatment.
In recent years, new chemotherapeutic drugs such as paclitaxel, platinum oxalate, topase inhibitor and Siroda are used for gastric cancer, and the efficiency of single drug is about 20%, and the combination can improve the effect of chemotherapy.
4.1.3 Drug therapy for advanced gastric cancer
Tomasello G et al. studied the role of sequential chemotherapy in advanced gastric cancer. Untreated patients received 4 cycles of TCFdd (docetaxel 70 mg/m2 d1, cisplatin 60 mg /m2 d1, calcium folinic acid 100 mg /m2 d1~2, fluorouracil 400 mg/m2 d1~2, fluorouracil 600 mg /m2 d1~2) followed by 4 cycles of COFFI (oxaliplatin 85 mg/m2 d1, irinotecan 140 mg/m2 d1, calcium folinic acid 200 mg/m2 d1, fluorouracil 400 mg/m2 d1, fluorouracil 2 400 mg/m2 d1), which had an overall remission rate of 60% and a median time to disease progression of 12.1 months.
Optimization of chemotherapy regimens for patients with advanced gastric cancer is an important guarantee for improving quality of life and prognosis, and it is important to draw lessons from the results of the above data from various clinical drug trials.
Whether the combination of drugs has value on the survival rate of patients, whether the chemotherapy regimen has a driving or blocking effect on the progression of advanced gastric cancer, and whether the far (near-term) toxic side effects of various types of drugs such as platinum, cytotoxic drugs, etc. have any effect on the survival quality of advanced patients are expected to be the direction of our further research.
In the design of scientific research, a multidisciplinary and integrated treatment approach can be used to spread out the thinking and extract the best solution to avoid detours.
4.2 The principle of surgical treatment is whole resection of part or all of the stomach including cancer foci and possibly infiltrated stomach wall, whole removal of lymph nodes around the stomach according to clinical staging criteria, and reconstruction of the digestive tract.
(1) Scope of gastric resection: the incision line of the gastric wall must be more than 5 cm from the edge of the tumor; the incision line of the duodenal side or esophageal side should be 3~4 cm from the pylorus or cardia.
(2) Removal of perigastric lymph nodes: the range of lymph node removal is indicated by D, and N indicates the station of perigastric lymph nodes. The lymph nodes in the first station are not completely cleared as D0, the lymph nodes in the first station are completely cleared as D1; the lymph nodes in the second station are completely cleared as D2, followed by D3.
The radical degree of gastric cancer surgery is divided into A, B and C. Grade A: D>N, the lymph node station removed by surgery is beyond the lymph node station with metastasis; there is no cancer cell infiltration within 1cm of the cut edge; Grade B: D=N, or there is cancer cell involvement within 1cm of the cut edge, which is also radical surgery; Grade C: only the primary foci and part of the metastatic foci are removed, and there is still tumor residue, which is non-radical surgery.
(3) Surgery mode: It is determined according to tumor site, progression degree and clinical stage. For early stage gastric cancer, due to the limited lesion and less lymph node metastasis, curative resection can be obtained by performing gastrectomy below D2, and laparoscopic or open partial gastrectomy is feasible.
For non-ulcerous depressed gastric cancer <1 cm and elevated mucosal cancer <2 cm in diameter, gastric mucosal resection can be performed under endoscopy.
5.Prognosis
The prognosis of gastric cancer is related to the pathological stage, site, tissue type, biological behavior and treatment measures of gastric cancer. The prognosis of early gastric cancer is much better than that of progressive gastric cancer.
According to bulk reports, the 5-year survival rate of standardized treatment for stage I gastric cancer is 82%-95%, 55% for stage II, 15%-30% for stage III, and only 2% for stage IV. Gastric tumors with small size, no invasion of the plasma membrane, no lymph node metastasis, and feasible radical surgery have a better prognosis.
The proximal gastric cancer of cardia and upper third of stomach has a worse prognosis than that of gastric body and distal gastric cancer. Currently, the diagnosis rate of early gastric cancer in China is very low, which affects the prognosis. Increasing the early diagnosis rate will significantly improve the 5-year survival rate of gastric cancer.