I. Overview
Gastric cancer is one of the most common malignant tumors in China, and the 2010 Health Statistical Yearbook shows that in 2005, the mortality rate of gastric cancer accounted for the 3rd place of malignant tumor mortality in China. The occurrence of gastric cancer is the result of the long-term effect of multiple factors. There are obvious regional differences in the incidence of gastric cancer in China, and environmental factors are dominant in the occurrence of gastric cancer, while host factors are subordinate. Studies have shown that H. pylori infection, diet, smoking and genetic susceptibility of the host are important factors affecting the occurrence of gastric cancer.
In order to further standardize the treatment behavior of gastric cancer in China, improve the level of gastric cancer treatment in medical institutions, improve the prognosis of gastric cancer patients and guarantee medical quality and medical safety, this specification is formulated. Gastric cancer referred to in this specification refers to adenocarcinoma of the stomach (hereinafter referred to as gastric cancer), including cancer of the gastroesophageal junction.
II. Diagnosis
The diagnosis and differential diagnosis of gastric cancer should be made by combining clinical manifestations, endoscopy and histopathological and imaging examinations of patients.
(I) Clinical manifestations
Gastric cancer lacks specific clinical symptoms, and early gastric cancer is often asymptomatic. The common clinical symptoms include discomfort or pain in upper abdomen, loss of appetite, emaciation, weakness, nausea, vomiting, vomiting blood or black stool, diarrhea, constipation, fever, etc.
(II) Physical signs
Early stage or part of locally progressive gastric cancer often has no obvious physical signs. In advanced gastric cancer patients, upper abdominal masses can be found, and when distant metastasis occurs, corresponding signs can appear according to the metastasis site. When upper gastrointestinal perforation, bleeding or gastrointestinal obstruction occurs, corresponding signs may appear.
(C) Ancillary examinations
1.Endoscopic examination
(1) Gastroscopy: It is a necessary examination means to confirm the diagnosis of gastric cancer, which can determine the location of tumor and obtain tissue specimens for pathological examination. If necessary, pigmented endoscopy or magnification endoscopy can be used as appropriate.
(2) Ultrasonic gastroscopy: It is helpful to evaluate the depth of gastric cancer infiltration and determine the status of perigastric lymph node metastasis, and is recommended for preoperative staging of gastric cancer. This examination is necessary for those who intend to perform minimally invasive surgery such as endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD).
(3) Laparoscopy: laparoscopy can be considered for those who suspect peritoneal metastasis or intra-abdominal dissemination.
2.Histopathological diagnosis
Histopathological diagnosis is the basis for confirming the diagnosis and treatment of gastric cancer. Patients diagnosed as invasive cancer by biopsy are subject to standardized treatment. If the depth of infiltration cannot be determined by biopsy pathology due to the limitation of biopsy sampling, patients who are reported as precancerous lesions or suspicious infiltration are recommended to repeat biopsy or combine with imaging results to further confirm the diagnosis and select treatment plan.
(1) Gastroscopic biopsy specimen processing
(1) Specimen pre-disposition: Immediately after the biopsy specimen is isolated, the specimen is spread out so that the basal level of the mucosa is adhered to the filter paper.
② Specimen fixation: placed in 10%-13% formalin buffer. The fixation time before embedding must be greater than 6 hours and less than 48 hours.
③ Paraffin embedding: Remove the filter paper and embed the tissue in vertical orientation.
④HE filming standard: trim the wax block, requiring 6-8 tissue surfaces to be cut consecutively and retrieved on the same slide. Routine HE staining, sealing the film.
(2) Pathological diagnostic criteria
①Low-grade intraepithelial tumor: the structure and cytology of mucosal glands are mildly heterogeneous, compared with the surrounding normal glands, the glands are densely arranged, the glandular cells appear pseudostratified, there is no or very little mucus, the nuclei are heavily stained, and the nuclear division phase appears.
High-grade intraepithelial tumor: the structure and cytological morphology of intra-mucosal glands were heavily heterogeneous (adenosquamous carcinoma in situ), and compared with the surrounding normal glands, the glandular ducts were densely arranged, the arrangement and polarity of glandular duct cells were significantly disordered, and on the basis of the low-grade intraepithelial tumor, co-walled or even sieve-like structures further appeared, lacking mucus secretion, with active nuclear division phase and focal necrosis, but without interstitial infiltration.
(③) Intramucosal carcinoma: i.e. intra-mucosal infiltrating carcinoma, irregular nests of glandular epithelial cells or isolated glandular epithelial cells infiltrating the interstitial layer of the mucosa lamina propria, confined within the mucosal muscle layer.
(4) Submucosal carcinoma: i.e., intramucosal infiltrating carcinoma continues to infiltrate deeper and penetrates the mucosal muscle layer to reach the submucosal layer without invading the intrinsic muscle layer of the stomach.
⑤ Early gastric cancer (T1N0/1M0): including intramucosal invasive carcinoma and submucosal invasive carcinoma, regardless of the presence or absence of regional lymph node metastasis.
(3) Pathological assessment
①Tissue specimen fixation criteria.
Fixative: 10%-13% neutral formalin fixative is recommended, avoid using fixative containing heavy metals.
Fixative volume: must be greater than 10 times the volume of the fixed specimen.
Fixation temperature: normal room temperature.
Fixation time: endoscopic biopsy specimens or mucosal resection specimens: greater than 6 hours, less than 48 hours. Gastrectomy specimens: fixed along the gastric greater curvature dissection spread, fixed time frame of more than 12 hours, less than 48 hours.
②Take the material requirements.
A, biopsy specimens.
Check the number of specimens sent to the clinic, send biopsy specimens must all be taken. Each wax block includes no more than 5 biopsy specimens. Wrap the specimen in gauze or soft permeable paper to avoid loss.
B. Endoscopic mucosal resection specimens.
The specimens will be fixed by the surgeon and the orientation will be marked. The size of the tumor and the distance of each orientation from the cut edge should be recorded. Perpendicular to the gastric wall, the specimen is cut in parallel at an interval of 0 or 3 cm and divided into tissue blocks of appropriate size, and it is recommended to take all the material in the same embedding direction. The corresponding orientation of the tissue block was recorded.
C. Gastrectomy specimens (see Annex 1 for description records of general examination).
a. Tumor and cutting edge: tumor tissues were fully sampled, depending on the size of tumor, depth of infiltration, different texture and color of the area were routinely sampled, tumor ≥ 4 blocks, containing 1-2 blocks of full thickness tumor in the deepest part of tumor infiltration, in order to judge the deepest level of tumor invasion. 1-2 pieces of tumor and paraneoplastic junction tissues were taken to observe the relationship between tumor and adjacent normal mucosa viewed by the naked eye. Cut distal and proximal surgical margins, routinely at least 1 block each. Early stage cancer sampling principle: cut all surgical resection specimens for filming, and should be accompanied with diagram to mark the location of the taken tissue blocks for reference during follow-up or consultation.
b. Lymph nodes: It is recommended that surgeons send lymph nodes in groups according to local anatomy and intraoperative views to facilitate the localization of lymph node drainage areas; in the absence of medical advice or markings from surgeons sending lymph nodes in groups, pathologists should detect lymph nodes in specimens according to the following principles: all lymph nodes should be taken, and it is recommended that the total number of lymph nodes in preoperative untreated cases should be ≥15. All lymph nodes that are negative to the naked eye should be sent intact, and lymph nodes that are positive to the naked eye can be partially excised and sent for examination.
c. Recommended tissue volume for sampling: no larger than 2×1, 5×0, 3 cm.
D. Principles of specimen handling and retention time frame after sampling.
a. Preservation of remaining specimens: Preserve the remaining tissue in the standard fixative, and always maintain adequate amount of fixative and formaldehyde concentration to avoid drying out of the specimen or tissue decay due to insufficient amount of fixative or reduced concentration, so as to be ready for additional sampling according to the diagnostic needs of microscopic observation, or to review the bulk specimen or additional sampling when clinical feedback is received after the issuance of the pathological diagnostic report.
b. Time limit for processing of remaining specimens: It is recommended that after 1 month of the issuance of the pathological diagnostic report, no clinical feedback is received, and no request for review due to disagreement of external consultation occurs, the hospital can process the specimens by itself.
(4) Pathological types
①The general types of early gastric cancer.
Ⅰ: augmented type
Ⅱa: surface elevated type
Ⅱb: flat type
Ⅱc: surface depression type
Ⅲ: depressed type
②The general types of progressive gastric cancer.
Bulging type: The main body of the tumor protrudes into the intestinal lumen.
Ulcerated type: The tumor reaches deep into or penetrates the muscle layer combined with ulceration.
Infiltrative type: The tumor infiltrates diffusely into all layers of the intestinal wall, thickening the local intestinal wall, but there is often no obvious ulcer or augmentation on the surface.
③Histological type.
A. WHO classification: the most commonly used histological typing method for gastric cancer (Annex 2).
B.Lauren classification: intestinal type, diffuse type, mixed type.
(5) Contents of pathology report
A. The pathology report of the biopsy specimen must include the following contents.
a.Basic information of the patient and information of the sending examination;
b, intraepithelial tumor (heterogeneous hyperplasia), report grading;
c. Suspicious infiltration: biopsy should be repeated and immunohistochemical staining should be performed to identify if necessary;
d. Early infiltrating carcinoma: suggest the depth of infiltration.
Clinicians should understand that the actual depth of infiltration may be difficult to confirm by histopathological examination of biopsy due to the limitation of biopsy sampling depth.
B. The pathology report of the endoscopic mucosal resection specimen must include the following
a. Basic patient information and delivery information;
b. Tumor size;
c, grading of intraepithelial tumor (heterogeneous hyperplasia);
d. For infiltrative carcinoma, histological typing, grading, depth of infiltration, cutting edge condition and vascular invasion should be reported.
pT1 low-differentiated carcinoma, vascular invasion, and positive cut margin should be re-surgically expanded for resection. In other cases, adequate endoscopic resection is sufficient, but regular postoperative follow-up is required.
Histologic features with poor prognosis include: hypodifferentiation, vascular and lymphovascular infiltration, and positive cut margins.
Positive cut margin is defined as: tumor less than 1mm from the cut margin or cancer cells visible at the cut margin of the electric knife.
C. The pathology report of surgical resection specimen must include the following contents.
a. Basic information of the patient and information of the delivery;
b. General information: tumor location, size, general type, depth of infiltration seen by the naked eye, distance between upper and lower cutting edge and tumor;
c. Degree of tumor differentiation (tumor typing and grading);
d. Depth of tumor infiltration (T-stage, T-stage or pT is decided according to the tumor cells with morphological basis. Mucus lake without cells in the specimen treated with neoadjuvant therapy is not considered as tumor residual) (see Annex 3 for TNM staging criteria);
e, the number of detected lymph nodes as well as the number of positive lymph nodes (N stage);
f. The status of the proximal cut margin and distal cut margin. If the tumor is very close to the incisional margin, the distance between the tumor and the incisional margin should be measured and reported under the microscope, and the tumor within 1 mm from the incisional margin should be reported as positive for the incisional margin;
g. The condition of vascular and nerve invasion;
h. Special tests that can help differential diagnosis and guide clinical treatment, including immunohistochemistry and molecular pathology tests, such as HER-2 test.
The clinician must fill out a detailed pathological diagnosis request form, truthfully describe the surgical findings and relevant clinical ancillary examinations and clearly mark the lymph nodes.
3.Laboratory examination
(1) Blood tests: blood routine, blood biochemistry, serum tumor markers and other tests.
(2) Urine, stool routine, fecal occult blood test.
4.Imaging examination
(1) Computed tomography (CT) scan: CT plain scan and enhanced scan have important values in evaluating the extent of gastric cancer lesions, local lymph node metastasis and distant metastasis, etc., and should be used as a routine method for preoperative staging of gastric cancer. In the absence of contraindications to the use of contrast agents, it is recommended to perform enhanced CT scan when the gastric cavity is well filled. The scanning site should include the primary site and possible metastatic sites.
(2) Magnetic resonance (MRI) examination: MRI examination is one of the important imaging tools. It is recommended for those who are allergic to CT contrast or those who suspect metastasis on other imaging examinations. MRI helps to determine the status of peritoneal metastasis and can be used as appropriate.
(3) Upper gastrointestinal imaging: It helps to determine the scope and functional status of the primary gastric lesion, especially air-barium double contrast imaging is one of the common imaging methods to diagnose gastric cancer. For patients suspected of pyloric obstruction, water-soluble contrast agent is recommended.
(4) Chest X-ray examination: it should include frontal and lateral phases, which can be used to evaluate the presence of lung metastases and other obvious lung lesions, and lateral phases can help to detect post-cardiac shadowing lesions.
(5) Ultrasonography: it is valuable for evaluating local lymph node metastasis and metastasis in superficial areas of gastric cancer, and can be used as a preliminary examination method for preoperative staging. Transabdominal ultrasonography can understand whether there are metastases in the abdominal cavity and pelvis of patients, especially ultrasonography can help identify the nature of lesions.
(6) PET-CT: It is not recommended for routine use. It can be used as appropriate for metastatic lesions that cannot be clearly identified by conventional imaging.
(7) Bone scan: not recommended for routine use. For patients with gastric cancer suspected to have bone metastasis, bone scan examination can be considered.
IV. Differential diagnosis
(I) Benign diseases: Gastric cancer has no characteristic symptoms and signs, and needs to be differentiated from benign lesions such as gastric ulcer, gastric polyp (gastric adenoma or adenomatous polyp), gastric giant crepitus, hypertrophic gastritis, warty gastritis, gastric mucosal prolapse, fundic venous tumor, sarcoidosis, etc.
(B) Other malignant tumors of the stomach: mainly distinguished from malignant lymphoma of the stomach, gastric mesenchymal tumor, gastric neuroendocrine tumor, etc. Those with liver metastasis should be distinguished from primary liver cancer.
V. Treatment
(I) Treatment principle
The principle of comprehensive treatment should be adopted, that is, according to the pathological type and clinical stage of the tumor, combined with the general condition and functional status of the patient, the multidisciplinary comprehensive treatment mode should be adopted, and the treatment means such as surgery, chemotherapy, radiotherapy and biological targeting should be applied in a planned and reasonable manner to achieve the purpose of radical or maximum control of the tumor, prolonging the patient’s survival and improving the quality of life.
1.For early stage gastric cancer without lymph node metastasis, endoscopic treatment or surgery can be considered according to the depth of tumor invasion, without adjuvant radiotherapy or chemotherapy after surgery.
2. Early gastric cancer with localized progressive stage or lymph node metastasis should be treated mainly by surgery. Depending on the depth of tumor invasion and whether it is accompanied by lymph node metastasis, direct radical surgery or preoperative neoadjuvant chemotherapy can be considered before radical surgery. Adjuvant treatment plan (adjuvant chemotherapy and, if necessary, adjuvant chemoradiotherapy) should be decided according to the postoperative pathological stage for locally progressive gastric cancer that has been successfully performed radical surgery.
3. Recurrent/metastatic gastric cancer should be treated with a comprehensive treatment based on drug therapy, and local treatment such as palliative surgery, radiotherapy, interventional therapy, radiofrequency therapy should be given at the appropriate time, and the best supportive treatment such as pain relief, stent placement and nutritional support should also be actively given.
(II) Surgical treatment
1.Surgical treatment principle
Surgical resection is the main treatment for gastric cancer and the only way to cure gastric cancer at present. Gastric cancer surgery is divided into radical surgery and palliative surgery, and radical resection should be strived for. Radical surgery for gastric cancer includes EMR, ESD, D0 resection and D1 resection for early gastric cancer, and (D2) and expanded surgery (D2+) for partially progressive gastric cancer. Palliative surgery for gastric cancer includes palliative resection of gastric cancer, gastrojejunostomy, jejunal nutrition tube placement, etc.
Surgical procedures should be performed to completely remove the primary lesion and thoroughly clear the regional lymph nodes. For gastric cancer with limited growth, the margin should be at least 3 cm from the lesion; for gastric cancer with infiltrative growth, the margin should be more than 5 cm from the lesion; for gastric cancer adjacent to esophagus and duodenum, the lesion should be removed as completely as possible, and intraoperative frozen pathological examination should be performed if necessary to ensure that no cancer remains in the margin. Nowadays, D (dissection) is still used to indicate the range of lymph node clearance, such as D1 surgery refers to the clearance of regional lymph nodes to station 1, D2 surgery refers to the clearance of regional lymph nodes to station 2, and if the requirement of lymph node clearance at station 1 is not met, it is regarded as D0 surgery.
Laparoscopy is a recently developed minimally invasive surgical technique, and its application in gastric cancer should be suitable for stage I patients at present.
2.Surgery style and indications
(1) Reduction surgery
The resection area is smaller than that of standard radical surgery.
(1) Endoscopic mucosal resection and endoscopic submucosal resection indications: highly differentiated or moderately differentiated, non-ulcerated, less than 2cm in diameter, no lymph node metastasis intra-mucosal carcinoma.
②Indications for gastrectomy D1: intramucosal carcinoma with a diameter of more than 2 cm, and gastric cancer invading the submucosa. Once lymph node metastasis appears, D2 resection should be performed.
(2) Standard surgery
D2 radical surgery is the standard surgery for gastric cancer. If the depth of tumor infiltration exceeds the submucosa layer (muscle layer or above), or if there is lymph node metastasis but it has not yet invaded the adjacent organs, the standard surgery (D2 radical surgery) should be performed.