Gastric cancer is the second most common malignant tumor in the world and in Japan. It also has a high mortality rate in Central and South America and the former Soviet Union. Fortunately, the mortality rate of gastric cancer in the United States has been declining significantly since the 1960’s. In the 1940’s, gastric cancer was the third deadliest malignancy in the United States. By 2007, the mortality rate had fallen to seventh and the incidence rate to fourteenth. Because of the high incidence of gastric cancer, Japan has conducted national screening to detect lesions at an early stage. Since 1983, Japan has been conducting screening of upper gastrointestinal tract angiography in groups over 40 years of age, which has led to a significantly higher detection rate of early and treatable gastric cancer. Early gastric cancer is defined as a lesion confined to the mucosa and submucosa, with or without lymph node metastasis. As a result of screening, the detection rate of early gastric cancer in Japan has increased from 10% in the 1960s to 60% today. Because of the low incidence of gastric cancer in the United States, the benefits of screening are not as great as in Japan. As a result, most gastric cancers in the United States are diagnosed at a progressive stage, with limited treatment options and a poor prognosis. Even so, early-stage gastric cancer accounts for 10% of all gastric cancers in the United States. The detection rate may be further increased if timely endoscopy is performed for high-risk groups. The main risk factors for gastric cancer include: – Pernicious anemia – Gastric ulcer – Chronic atrophic gastritis – Gastric epithelial intestinal hyperplasia – Previous surgery such as vagotomy, partial gastrectomy, gastrointestinal anastomosis In addition, gastroscopy should be considered in all patients over 40 years of age with dyspepsia. The probability of detecting gastric cancer in this population is about 2%. Selection of patients for endoscopic treatment of early gastric cancer 1. Endoscopic staging In order to strictly grasp the indications for endoscopic treatment of early gastric cancer, a set of very detailed staging methods has been proposed in Japan. Japanese and international gastric cancer associations recommend that early gastric cancer lesions should be accurately described in endoscopic and pathological reports. The endoscopic report must include the number, size and location of lesions. In addition, the morphology of the lesion as seen by the naked eye should be described according to Figure 1. –Endoscopic staining technique It is recommended to stain and mark the abnormal mucosal areas seen endoscopically, i.e. pigmented endoscopy technique. The most commonly used dye for the stomach and colon is 0.5% to 1% indigo solution. The combination of endoscopic staining techniques and high magnification images can provide a clearer and more detailed response to the state of the gastric mucosa and may enhance the integrity of the endoscopic resection due to the ability to describe the extent and characteristics of the lesion in a relatively pure manner. –Ultrasound endoscopic imaging techniques have been applied to differentiate early gastric cancer from progressive gastric cancer. kwee et al. conducted a systematic review of the literature on the accuracy of ultrasound endoscopy in assessing the depth of gastric cancer infiltration. However, due to the heterogeneity of patients enrolled in each study and differences in ultrasound endoscopic techniques, it is not possible to accurately evaluate whether ultrasound endoscopy can effectively differentiate between intramucosal and deeper tumors. –Virtual gastroscopy Studies have been performed to evaluate the accuracy of virtual gastroscopy with computerized 3D imaging technology for gastric cancer diagnosis. However, the results were similar to ultrasound endoscopy, and the heterogeneity of the enrolled lesions in the early studies did not show better accuracy compared to ultrasound endoscopy. 2. Pathological staging The endoscopically excised mucosa should be fixed on a flat soft plate to precisely record the size, shape and location of the lesion, which is then fixed with formaldehyde and pathologically sectioned at 2-mm intervals after recording the following information: – Histological type – Maximum diameter of the lesion – Presence of the following factors : ulceration, lymphovascular infiltration, vascular infiltration If no tumor remains in the vertical cut margin, the depth of infiltration should be described according to the example in Figure 2. The depth of submucosal infiltration requires precision to the micrometer (sm1 < 500 μm, sm2 ≥ 500 μm). The standard indications for endoscopic treatment of early gastric cancer were proposed by the Japan Gastric Cancer Association (JGCA) in 1998 before the introduction of ESD technology: - Highly or moderately differentiated adenocarcinoma - Lesion confined to the mucosal layer - Maximum lesion diameter <20 mm - The probability of lymph node metastasis after treatment according to the above criteria is only 0.36%. In 2000, Gotoda et al. conducted a controlled study of 3016 cases of intramucosal and 2249 cases of submucosal cancers treated with surgical intervention and found that lymphovascular or vascular invasion was the most important factor suggesting lymph node metastasis. Based on these findings, the indications for endoscopic treatment of early gastric cancer have been expanded. The guideline was accepted in the guideline published by the Japanese Gastric Cancer Association in 2004, but was recommended to be carried out only in clinical trials. Expanded indications for endoscopic treatment of early gastric cancer include: ① Highly or moderately differentiated adenocarcinoma without vascular or lymphovascular infiltration (Table 1) - Intramucosal (m1, m2, m3) or minimally infiltrated submucosal (sm1 < 500 μm) cancer without ulcer formation: any size; whole resection is expected to be feasible - Intramucosal (m1, m2, m3 ② Undifferentiated adenocarcinoma without vascular or lymphovascular infiltration (Table 2) - Intramucosal (m1, m2, m3) or minimally infiltrated submucosal (sm1<500μm) carcinoma without ulcer formation: ≤2cm in diameter; expected to be feasible En bloc resection The above indications for expansion continue to be refined. For example, Ishikawa et al. concluded that any infiltrating submucosal gastric cancer should be treated surgically, and endoscopic resection can be considered for lesions with ulcers less than 20 mm in diameter. Since staging can only be clarified after completion of endoscopic treatment, patients should be fully informed before excisional biopsy of the lesion: whether endoscopic resection is complete and whether surgical remedy is required is determined by the pathology report. Again, the goal of the first endoscopic treatment of early gastric cancer is complete radical resection. oda et al. found higher rates of radical resection and 3-year postoperative recurrence-free survival with ESD compared with EMR (73.6% vs. 61.1% and 97.6% vs. 92.5%). The authors concluded that the better outcome of ESD treatment was associated with whole-block resection and negative pathological margins.Takanaka et al. verified this conclusion. IV. Complications 1. Bleeding The most common complications of EMR and ESD are bleeding and perforation. Bleeding can be classified as intraoperative and delayed (within 30 days after surgery) bleeding. Intraoperative bleeding can be controlled by electrocautery or clamping. Delayed postoperative bleeding, which is characterized by vomiting blood or black stool, mostly occurs within 12 hours after surgery and requires emergency endoscopic surgery to stop the bleeding. Depending on the definition, the probability of postoperative bleeding after endoscopic treatment of early gastric cancer ranges from 1.5% to 24%. oda et al. analyzed 714 patients with endoscopic resection and found that only one case was treated with postoperative blood transfusion. Perforation Perforation of the gastric wall is the most serious complication after EMR and ESD, with incidence rates of 1% and 3%, respectively. Intraoperative perforation can be closed with endoscopic clips. Perforations with a diameter of 25 mm can be repaired with an endoscopic clip using omentum. Patients presenting with clinical signs of pneumoperitoneum may have air extracted by puncture. After completion of repair, nasogastric tube decompression, empirical application of antibiotics, and acid suppression are required, with close clinical observation. In case of unstable vital signs or diffuse peritonitis, open exploration is required for repair. 714 endoscopic treatments were completed by Oda et al. and only 16 endoscopic perforation repairs were performed without open exploration. V. Postoperative management Short-term postoperative application of proton pump inhibitors and thioglycollate is required to promote healing of the resection site. Early gastric cancer often has multiple foci, and heterochronic primary foci may appear even after endoscopic resection. Therefore, postoperative review is crucial. Two studies have shown the benefit of annual review of gastroscopy for timely detection of simultaneous or heterochronic multiple primary foci, allowing timely treatment to preserve gastric function. Prognosis In 2005, Uedo et al. published a study comparing the long-term outcome of conventional surgery and endoscopic treatment for well-differentiated early-stage small intramucosal gastric cancer (<20 mm). 5-year and 10-year survival rates were both 99%. After the publication of this study, EMR became part of the routine treatment for well-differentiated small intramucosal gastric cancer in Japan (Table 3). Some earlier retrospective studies on the efficacy of endoscopic expanded indications for gastric cancer also yielded encouraging findings. oda et al. reported a 100% disease-specific survival rate at 3 years after surgery and an overall recurrence-free survival rate of 94.4%. the recurrence-free survival rate for ESD was significantly higher than that for EMR (97.6% versus 92.5%). A prospective phase II clinical study (JCOG 0607) has been initiated in Japan, which aims to clarify the efficacy of expanded indications ESD. This study will be the first prospective study to report 5-year survival rates after ESD. The results of this study may be decisive evidence on whether ESD can become the standard of care for early gastric cancer. ESD has been shown to be safe and feasible among elderly gastric cancer patients with poor general condition. ESD may also be considered for recurrent lesions after previous EMR. VII. Conclusion Early gastric cancer refers to malignant tumors with lesions confined to the mucosa or submucosa, with or without lymph node metastasis. Compared with surgical procedures, endoscopic procedures (EMR and ESD) have good therapeutic effects and very low postoperative mortality. Strict control of endoscopic treatment indications is the key to good prognosis. In contrast, the expanded indications for ESD still need to be supported by more long-term prognostic evidence. Patients must also be informed that surgical treatment is required if postoperative pathology suggests deeper lesion infiltration.