”The growth of gastric cancer is infinite, but the scope of surgery is limited; to control the infinite growth of gastric cancer within the limited scope of surgery —- Neoadjuvant chemotherapy for gastric cancer”. Throughout the history of gastric cancer treatment, people initially treated gastric cancer with gastrectomy, focusing on the resection of the primary focus, and clinical concerns were mainly about the safety of gastrectomy and the rationality of the reconstruction of the digestive tract, without active treatment of lymph node metastasis. Subsequently, Japanese scholars began to explore radical surgery for gastric cancer, and systematic lymph node removal was performed on the basis of adequate gastrectomy to improve the therapeutic effect of gastric cancer to a certain extent. In the past half century, as radical surgery for gastric cancer has been widely and intensively performed, it has been gradually recognized that the therapeutic effect of surgery on gastric cancer is still limited and not proportional to the infinite expansion of the scope of surgery. Therefore, in order to further improve the therapeutic effect of gastric cancer, a comprehensive treatment based on surgery has emerged, and neoadjuvant chemotherapy has become an important part of clinical research on gastric cancer. The clinical implementation of neoadjuvant chemotherapy for gastric cancer has only a history of nearly 20 years, and its development was slow in the early years due to the uncertainty of its efficacy, so there are still many problems in this field that need to be further studied and explored in clinical practice. After Feri proposed the concept of neoadjuvant chemotherapy in 1982, Wilke took the lead in implementing neoadjuvant chemotherapy in 1989, selecting 35 cases of unresectable gastric cancer after surgical exploration, treated with EAP (etoposide, adriamycin, cisplatin) regimen, with the result that 69% were effective and 20 of them were resected by stage II surgery. The MAGIC trial, which has had a major impact on the comprehensive treatment of gastric cancer in recent years, involved nine centers in the United Kingdom, the Netherlands, Germany, and Brazil, and enrolled cases of resectable gastric cancer and lower esophageal cancer with clinical stage II or higher. A total of 503 cases were enrolled in the study, of which 74% were gastric cancer cases. The study was randomly divided into a perioperative chemotherapy group (250 cases) and a control group (253 cases), with the former group receiving 3 courses of preoperative chemotherapy with ECF (epiaminomycin, cisplatin, 5-FU) and then surgery, and both groups receiving postoperative adjuvant chemotherapy with ECF. The results found that perioperative chemotherapy increased the 5-year survival rate from 23% to 36% of patients. Although the study still has shortcomings in the standardization of gastric cancer surgery, the accuracy of clinical staging before treatment, and the toxicity of chemotherapy, the 2009 edition of the NCCN guideline cites it as Class 1 evidence because of its rigorous design, multicenter large sample study, and control group, which still has high credibility. Based on the results of this study, neoadjuvant chemotherapy is recommended for cases above T2 (infiltrating myeloid layer), M0 (no distant metastases), with or without lymph node metastases, and the recommended chemotherapy regimen is ECF or ECF modified regimen. Due to the limitation of treatment effect, chemotherapy cannot replace surgery and can only be used as an adjuvant treatment to surgery. Obviously, neoadjuvant chemotherapy is generally not necessary for early-stage gastric cancer because the effect of surgical treatment is more satisfactory. In advanced gastric cancer with distant or extensive metastasis, such as peritoneal seeding and supraclavicular lymph node metastasis, it is still controversial whether surgery is needed after chemotherapy even if the cancer shrinks significantly. Therefore, clinically, it is customary to treat locally progressive stage II, IIIa, IIIb and some stage IV gastric cancer cases as the main target of neoadjuvant chemotherapy, which is in line with the 2009 NCCN guidelines. Although the 2009 NCCN guidelines recommend the ECF regimen or ECF modified regimen as the first choice of perioperative chemotherapy for gastric cancer based on the results of the MAGIC trial, the exploration of efficient and ideal neoadjuvant chemotherapy is still an important part of clinical research for gastric cancer. In recent years, many clinical studies and explorations on neoadjuvant chemotherapy for gastric cancer have been conducted by scholars from different countries. In the ASCO meeting in 2007, Boige reported the preliminary results of a randomized controlled clinical study of 224 cases of gastric cancer enrolled in 28 centers in France. The results suggest that neoadjuvant chemotherapy with the FP regimen can also improve the survival rate of gastric cancer, with 5-year survival rates of 38% and 24%, respectively. Since 2002, we have adopted the combined arteriovenous administration of FLEEOX (intravenous 5-FU and calcium folinic acid; arterial intervention with local injection of VP-16, epoetin and oxaliplatin) for neoadjuvant chemotherapy and achieved good results, with an efficiency rate of about 80% in the imaging evaluation. Chemotherapeutic drugs can be divided into cycle-specific drugs and cycle-nonspecific drugs. The former, such as 5-FU, has a therapeutic effect on cancer related to the time of action, and the time of administration is the main factor affecting the efficacy, and is suitable for slow sedation; the latter has a strong and rapid effect, and the concentration of the drug is the main factor affecting the efficacy, and the number of cancer cells killed increases logarithmically after the concentration increases. The combined intra-arterial and arteriovenous drug delivery method we use is based on the characteristics of the two types of drugs, intravenous slow drip 5-FU to maintain its duration of action, while taking advantage of the preoperative vascular and lymphatic reflux system, the arterial intervention of oxaliplatin, epi-amycin and VP-16 to increase their local concentrations, through the different routes of arteriovenous drug delivery to fully exploit the pharmacological effects of the two types of drugs. 16 has synergistic effects with platinum drugs and forms a high concentration of EEOX (VP-16, epi-adriamycin and oxaliplatin) regimen with oxaliplatin and epi-adriamycin at the administered site, similar to EAP (VP-16, adriamycin and cisplatin) regimen which is more effective in gastric cancer in terms of drug combination. The sensitivity of a chemotherapeutic drug to cancer cells is inherent, and according to the traditional oral or intravenous route and mode of administration, the way to improve the effect of chemotherapy mainly lies in the development of new drugs or combination of drugs, which is costly and difficult to develop new drugs. Combination of drugs is to optimize and combine the existing drugs according to their action characteristics, and to combine them in a reasonable way in order to achieve synergistic effects between them. The major difference between preoperative and postoperative is that the vascular and lymphatic return systems related to gastric cancer infiltration and metastasis are still sound, so neoadjuvant chemotherapy with combined arteriovenous drug delivery fully utilizes the advantages of these, and the experience and advantages of combined drugs can be drawn upon when selecting drugs, which may be more suitable for preoperative chemotherapy. 2, pre-treatment staging diagnosis: selection of reasonable treatment must rely on accurate preoperative staging diagnosis, obviously, pre-treatment staging diagnosis is very important for clinical implementation of neoadjuvant chemotherapy. Unnecessary chemotherapy damage can affect surgery and postoperative recovery, so cases receiving neoadjuvant chemotherapy must be screened by accurate clinical staging diagnosis before treatment to avoid patients receiving inappropriate treatment. This staging diagnosis is even more important when screening cases for clinical studies, as an inaccurate staging diagnosis can lead to imbalance in the enrolled cases, affect the comparison results, and even mislead the clinical understanding of neoadjuvant chemotherapy. In addition, pre-treatment staging diagnosis is also the basis for clinicians to understand comprehensive treatment and accumulate clinical experience. In the past decades, people took surgery as the starting point of gastric cancer treatment and explored a more reasonable mode of surgical treatment for gastric cancer with postoperative pathology as the “diagnosis”. These models are based on the postoperative pathological results of large number of gastric cancer cases, the incidence of lymph node metastasis and the distribution pattern of positive lymph nodes. In the model of comprehensive treatment for gastric cancer, neoadjuvant chemotherapy is the starting point of treatment for patients, and the clinical diagnosis of gastric cancer before treatment becomes an important basis for assessing the efficacy and even prognosis. After the “destruction” of neoadjuvant chemotherapy, cases with effective treatment show different degrees of remission, partial or complete necrosis of cancer tissues, and the postoperative pathological staging cannot reflect the patient’s true “Ho cancer” situation before treatment, so the clinical “gold standard” for evaluating the true extent of gastric cancer is lost. The “gold standard” for evaluating the real degree of progression of gastric cancer has been lost clinically. The more significant the effect of chemotherapy, the more obvious this situation becomes. Whether adjuvant chemotherapy is needed after surgery and the assessment of prognosis can only be based on the clinical stage before receiving chemotherapy. This is also the basis for accumulating successful experience, summarizing failures, and revising treatment patterns in clinical practice. Although the research on preoperative diagnosis of gastric cancer has received much clinical attention in recent years, its development is far less than the clinical needs. In addition to further improving the accuracy of diagnosis, rigorous clinical trials of neoadjuvant chemotherapy should also standardize the clinical diagnosis before treatment. Currently, many clinical trials only describe the clinical staging of selected cases, but rarely specify the specific method of clinical staging. For gastric cancer, the diagnosis of infiltration depth by ultrasound endoscopy and other methods can basically meet the clinical needs, but the more confusing is the diagnosis of the degree of lymph node metastasis. At present, the common international staging method for gastric cancer is the TNM staging method of UICC in 1997, which is based on pathological findings and the number of lymph node metastases as the staging of metastasis. However, it is difficult to observe all metastatic lymph nodes before surgery, and some lymph nodes in some areas are not visible at all on CT. Based on this result, most of the progressive gastric cancers can only be diagnosed as N0 or N1 based on the number of lymph nodes found on CT before surgery, and there are few cases of N3 or N2. Therefore, before neoadjuvant chemotherapy, we use the group localization method to assess the degree of lymph node metastasis in gastric cancer, and determine the degree of lymph node metastasis by identifying the anatomical structures such as important blood vessels around the stomach and the location of metastatic lymph nodes on CT. Determining the degree of metastasis by location may be more suitable for clinical diagnosis before treatment. 3.Evaluation of efficacy: Undoubtedly, observation of the effect on survival rate is an indisputable index for evaluating the effect of neoadjuvant chemotherapy, but the period required to observe the index related to survival rate is too long, which is not conducive to timely clinical summary and accumulation of experience and correction of treatment plan, so the evaluation of imaging and histology is a convenient and direct objective index. Among them, CT is simple, economical and practical, and can observe the cross-section of tumor and metastatic lymph nodes, and calculate the change of tumor size before and after treatment, which is the most common method to evaluate the treatment effect. At present, the common criteria for evaluating the efficacy of treatment are RECIST (response evaluation criteria in solid tumor) and the evaluation criteria for radiotherapy in the Japanese Statute for the Management of Gastric Cancer. The RECIST criteria were developed in 2000 by several western oncology research groups on the basis of the 1979 WHO evaluation criteria, and the sum of all measurable lesion lengths before and after treatment was calculated for comparison. Progressive Disease); and those who do not meet the criteria of PR and PD are considered stable (SD: stable disease,). The method in the Japanese Statute for the Management of Gastric Cancer is to measure the maximum diameter of the tumor and the longest diameter of the tumor perpendicular to the maximum diameter, and calculate the product of the two directions. The difference between the product before and after treatment and the ratio of the product before treatment was calculated as the shrinkage rate of the tumor. The tumor disappears completely as CR; the tumor shrinks more than 50% as PR; the tumor shrinks less than 50% as no change (NC: No Change); the tumor continues to grow as PD. Grade3 (severe: complete necrosis and disappearance of cancer tissue), Grade2 (moderate: more than 2/3 change of cancer tissue necrosis), Grade1 (mild: less than 2/3 change of cancer tissue necrosis) and Grade0 (ineffective: no change of cancer tissue necrosis). In clinical practice, there are many problems that cannot be ignored when observing the efficacy of treatment. When observing the change of tumor size before and after treatment by CT, the maximum cross-sectional area after treatment is often not completely overlapped with the same level before treatment. The influence of breathing on the CT scan plane is one of the reasons. The stomach is an intra-abdominal organ, and compared with the pancreas, kidneys and other retroperitoneal organs, it is relatively free and moves up and down with the breathing movement. In addition, changes in the tumor itself also have an effect on this. A highly invasive gastric cancer may cause the stomach wall to shorten, stiffen, and lose elasticity, especially when the primary site is fused with the adjacent small curved metastatic lymph nodes. After treatment, the cancer tissue is necrotic, the primary foci and metastases both shrink, the constricted stomach wall opens up, and the position of the cancer on the stomach wall changes accordingly. The more severe the contraction of the stomach wall before treatment, the better the treatment effect, the more obvious this phenomenon is. In some cases, the primary site and metastatic lymph nodes are closely fused together before treatment, and the maximum cross-section of both can be observed at the same level, while the maximum cross-section of both may be located at different levels of the CT scan after treatment, when the stomach wall is fully dilated. Therefore, it is better to observe the maximum cross-sections of the primary foci and metastases when comparing the changes of tumors before and after treatment, and the maximum cross-sections of the tumors may not necessarily coincide at the same level of CT scan when their positions in the abdominal cavity change before and after treatment. Many details of the evaluation of efficacy by CT are still not specified in the evaluation criteria. In some cases, the cancer tissue is completely necrotic after treatment, but the thickened scar tissue still exists, and the contour of this thickened scar tissue cannot be confirmed as CR on CT, which may lead to a discrepancy between CT results and histological findings. The active growth of cancer tissue can be inferred from the degree of enhancement of the cancer tissue on CT-enhanced scans, but in-depth studies are needed to evaluate the efficacy of the treatment. The complete disappearance of metastatic lymph nodes after chemotherapy can be considered as CR; what kind of changes in the primary foci can be considered as CR; only cases with complete necrosis or perforation of the primary foci can be considered as complete disappearance of cancerous tissues on CT; can thickened gastric wall be considered as CR when it is the same thickness as normal gastric wall after chemotherapy; all these details are worthy of in-depth study in clinical work to further improve the evaluation criteria. These details are worthy of further study and improvement of evaluation criteria in clinical work. Neoadjuvant chemotherapy for gastric cancer has only a history of nearly 20 years. In the early years, it was not easy to be clinically accepted due to the limitation of efficacy and toxic reactions, so its development was slow. In recent years, with the development of new drugs, new therapies and a large number of clinical trials, neoadjuvant chemotherapy for gastric cancer is gradually gaining attention. With the widespread clinical application and in-depth clinical research, many problems will be properly solved.