A clinical guideline for the endoscopic management of gastric cancer and precancerous lesions, published in a recent issue of Gastrointest Endosc.
Pre-cancerous lesions of the stomach
1. Gastric polyps
(1) Sporadic gastric epithelial polyps
Endoscopic changes cannot be used to differentiate the histologic classification of gastric polyps; therefore, biopsy should be performed when polyps are found endoscopically. Studies have shown that the vast majority of gastric epithelial polyps are fundic gland polyps (FGPs) or hyperplastic polyps. Sporadic FGPs may be associated with long-term use of proton pump inhibitors, but the risk of cancer is not increased in patients with non-familial adenomatous polyposis (FAP) who present with FGPs.
In contrast, hyperplastic polyps are associated with an increased risk of gastric carcinogenesis. Heterogeneous hyperplasia and malignancy are found in 5-19% of patients with hyperplastic polyps, so guidelines in some countries recommend resection of hyperplastic polyps larger than 0.5-1 cm in diameter. Numerous studies have shown that hyperplastic polyps larger than 1 cm in diameter and with a tip are risk factors for heterogeneous hyperplasia.
In addition, adenomatous polyps have the potential to develop into malignant tumors. Gastric adenomatous polyps should be resected endoscopically when circumstances permit, but follow-up of postoperative patients reveals recurrence rates of up to 2.6% and gastric cancer in 1.3% of patients. Compared to EMR, endoscopic submucosal resection reduced tumor recurrence but increased the incidence of other adverse events.
Endoscopy should be performed one year after adenomatous polypectomy and every 3-5 years thereafter. Hyperplastic and adenomatous polyps may develop in the setting of HP infection and environmental sexualized atrophic gastritis and should be excised at this time.
(2) Gastric polyps in FAP and Lynch syndrome
Gastric polyps are common in individuals with FAP, with the most common gastric polyps being FGPs, which are seen in 88% of children and adults with FAP. Adenomas can also occur in patients with gastric FAP and are often solitary, fixed and located in the gastric sinus. In addition, patients with familial polyposis syndrome often develop adenocarcinoma of the stomach associated with FGPs. However, the data on the risk of gastric cancer in patients with FAP and Lynch syndrome vary from country to country and are even contradictory.
Gastrointestinal epithelial metaplasia and heterotypic hyperplasia
Studies have shown that patients with gastrointestinal epithelial metaplasia (GIM), a precancerous lesion that may be associated with HP infection, smoking, and a high-salt diet, have a 10-fold higher risk of developing gastric cancer than the normal population. Two studies in the United Kingdom found that the incidence of gastric cancer among patients with GIM was as high as 11%, and that endoscopic surveillance can help with early detection of tumors and improve survival.
In addition, patients with GIM have a significantly higher risk of developing cancer when they have high heterogeneous hyperplasia (HGD). A recent European study showed that if low-grade heterogeneous hyperplasia is found in patients with GIM, EGD should be repeated and biopsied several times within 1 year, and endoscopic surveillance can be suspended when two consecutive endoscopies and biopsies do not reveal heterogeneous hyperplasia.
HGD can be complicated by invasive adenocarcinoma and 25% of patients with HGD will progress to adenocarcinoma within one year, therefore patients diagnosed with HGD should undergo surgery or endoscopic resection. However, it is controversial whether patients diagnosed with HGD must undergo empiric HP therapy.
3. Pernicious anemia
Pernicious anemia in patients with gastric adenocarcinoma may be associated with type A atrophic gastritis, and studies have found that the risk of pernicious anemia is highest in the first year after the diagnosis of gastric adenocarcinoma. However, the benefit of using endoscopic surveillance for pernicious anemia remains unproven. In light of recent studies, ASGE recommends endoscopy after the diagnosis of pernicious anemia, with or without upper gastrointestinal symptoms.
4. Gastric carcinoid tumors
Gastric carcinoid tumors can be classified into 4 types: type 1 is characterized by multiple, highly differentiated and associated with type A chronic atrophic gastritis; type 2 is characterized by multiple, highly differentiated and associated with Zoe’s syndrome and multiple endocrine adenoma formation; type 3 is characterized by solitary, highly differentiated and disseminated; type 4 is characterized by solitary and low differentiation.
The endoscopic evaluation of gastric carcinoid tumors should include the size, number, and distribution of the carcinoid tumors. Aspiration of gastric fluid for PH measurement and rapid serum gastrin level testing can be helpful in grading gastric carcinoid tumors when patients are not taking medications that affect gastrin levels. Regulatory strategies include endoscopic testing alone, endoscopic resection of small numbers of tumors, and surgical resection. Once a gastric carcinoid tumor has been diagnosed endoscopically, EUS helps to determine the depth of invasion and thus whether to consider EMR.
Type 1 gastric carcinoid tumors are more common clinically and often present with a benign course.1 The 5- or 10-year survival rates for type 1 gastric carcinoid tumors are not different from the general population, and clinical management includes endoscopic surveillance as well as endoscopic resection.
The incidence of type 2 gastric carcinoid tumors does not differ between men and women, and lymph node metastases are present in 10%-30% of patients at the time of disease detection.
Type 3 gastric carcinoid tumors are often detected at an advanced stage, and the 5-year survival rate is often less than 50%. Because of the high incidence of lymph node infiltration, all type 3 gastric carcinoid tumors should be considered for surgery.
type 3 gastric carcinoid tumors should be considered for surgical resection. Endoscopic resection should only be considered if the tumor is small (<1 cm) and highly differentiated. < p="">
The prognosis for type 4 gastric carcinoid tumors is poor, with a 1-year survival rate of only 50% after diagnosis. For all type 4
type 4 gastric carcinoid tumors, surgical treatment should be considered. Endoscopic surveillance should be performed after surgery or endoscopic resection, and some experts suggest that endoscopy should be performed preferably every 1-2 years.
5.After gastric surgery
Patients with benign gastric or duodenal ulcers are at elevated risk of developing gastric cancer after undergoing partial gastrectomy. Endoscopic follow-up studies have found that 4-6% of these surgical patients develop gastric cancer and that the process of heterogeneous hyperplasia to cancer occurs. In addition, studies have shown an increased risk of gastric cancer 15-20 years after the initial surgery.
Malignant tumors of the stomach
1. Adenocarcinoma
(1) Diagnosis
Adenocarcinoma is a common malignant tumor of the stomach that presents primarily as a mass, but can also present as a refractory gastric ulcer or a diffuse infiltrative type (leathery stomach). The gold standard for the diagnosis of gastric cancer is endoscopic mucosal biopsy, which detects tissue at the mass or abnormal mucosa in general, but in malignant gastric ulcer mainly detects at least 7 tissues at the edge of the ulcer and at the base of the ulcer.
The leathery stomach is difficult to diagnose because it mainly involves the submucosa and lamina propria. Sampling methods include: “tunnel biopsy”, in which a mucosal defect is artificially created by mucosal biopsy, followed by sampling of deeper tissue using biopsy forceps; bulk mucosal and submucosal biopsy sampling, in which samples are taken by capsulectomy; and EUS-FNA or core tube aspiration.
(2) Staging
Once the diagnosis of gastric cancer is established, cross-sectional imaging should be performed to facilitate staging. EUS-FNA can be used to stage localized areas when the tumor has not metastasized. EUS staging of gastric cancer is in accordance with the American Cancer Society TNM staging. When using EUS staging, one should first determine if the tumor is metastatic (M), such as if the liver or other parenchymal organs are involved. Whenever possible, these lesions need to be sampled using FNA.
In the absence of metastasis, the use of EUS staging should focus on regional and non-regional lymph node (N) staging and primary tumor (T) staging. A recent meta-analysis investigating the role of EUS in the staging of gastric cancer found that EUS-FNA was more likely to detect malignant lymph nodes than EUS alone.
(3) Endoscopic treatment
Cancer screening in people at high risk of developing gastric cancer facilitates the detection of patients with early gastric cancer (EGC), which can be treated endoscopically. Recent studies have found that the rate of whole-block resection by ESD in EGC patients can reach 87.7%, while the rate of significant bleeding and perforation are only about 1%. In addition, meta-analysis showed that ESD is better than EMR in terms of complete resection, curative resection and local recurrence, but ESD is more prone to intraoperative bleeding and perforation.
(4) Disease remission
Malignant gastric outlet obstruction due to gastric cancer may complicate malignant tumors of the gastric, duodenal and pancreaticobiliary tracts and significantly affect the quality of life and nutritional status of patients. Some studies have shown that endoscopic stent placement is safe and effective in relieving malignant gastric outlet obstruction.
However, other studies have shown that although endoscopic stent placement facilitates rapid return to diet, gastrojejunostomy is more effective in achieving long-term remission. Gastric cancer patients undergoing systemic chemotherapy can have prolonged upper gastrointestinal bleeding, and recent studies have found that endoscopic spraying of hemostatic drugs may help improve the condition.
2. Mucosa-associated lymphoid tissue lymphoma
Extraneural marginal zone B-cell lymphoma is a low-grade B-cell lymphoma that can be found in the mucosa-associated lymphoid tissue (MALT) of the stomach, lung, small intestine, and other organs. Gastric MALT lymphoma is pathologically completely different from gastric adenocarcinoma, but can present with the same symptoms (such as dyspepsia, weight loss, or upper gastrointestinal bleeding). The endoscopic changes of gastric MALT lymphoma are varied and the diagnosis can be confirmed by mucosal biopsy.
The majority of patients with gastric MALT lymphoma have HP infection, and the mechanism may be that chronic inflammation associated with HP leads to MALT lymphoma by triggering clonal proliferation of B cells. Low-grade MALT lymphoma should be treated with HP eradication, and 80% of patients achieve clinical remission as a result.
EUS provides an accurate assessment of the extent of lymphoma infiltration of the gastric wall and the involvement of regional lymph nodes, and can therefore be used to gather prognostic information.
3. gastrointestinal mesenchymal tumor (GIST)
GIST is the most common type of gastric mesenchymal tumor and EUS-FNA is commonly used for its diagnosis.GIST with malignant potential is characterized by a diameter greater than 2 cm, lobulated or irregular margins, invasion of adjacent structures, and inhomogeneous density.EUS direct sampling is useful for differentiating GIST from other subepithelial lesions, but is not ideal for predicting malignant potential. Spindle cells can be found in cytologic specimens of GIST obtained using EUS-FNA, and immunohistochemical staining can further confirm the diagnosis.
In general, symptomatic GIST lesions should be surgically resected, especially if the lesion is the cause of bleeding. Surgical resection should be considered in asymptomatic GIST patients with tumors larger than 2 cm in diameter or with tumor features suggestive of malignant potential on EUS. Instead, consider follow-up surveillance with EUS