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 Helicobacter pylori (H. pylori) infection, diet, smoking and host genetic susceptibility are important factors affecting the occurrence of gastric cancer. Li Baodong, Department of General Surgery, Henan Cancer Hospital
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 gastric adenocarcinoma (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 the clinical manifestations, endoscopy, histopathology and imaging examination of patients.
(A) Clinical manifestations. Gastric cancer lacks specific clinical symptoms, and early gastric cancer is often asymptomatic. The common clinical symptoms include discomfort or pain in the 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 in case of distant metastasis, corresponding signs can appear according to the metastasis site. In case of upper gastrointestinal perforation, bleeding or gastrointestinal obstruction, corresponding signs may appear.
(iii) Ancillary examinations.
1. Endoscopic examination.
(1) Gastroscopy: It is a necessary examination 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 useful for evaluating the depth of gastric cancer infiltration and judging 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 procedures such as endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD).
(3) Laparoscopy: For those who suspect peritoneal metastasis or intra-abdominal dissemination, laparoscopy can be considered.
2. Histopathological diagnosis.
Histopathological diagnosis is the basis for the confirmation of diagnosis and treatment of gastric cancer. Patients diagnosed as invasive cancer by biopsy are treated in a standardized way. 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 choose 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 adheres 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.
(1) Low-grade intraepithelial tumor: the structure and cytological morphology of the 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), with dense glandular ducts, significantly disordered arrangement and polarization of glandular duct cells compared with the surrounding normal glands, and further appearance of co-mural or even sieve-like structures on the basis of low-grade intraepithelial tumors, lack of mucus secretion, active nuclear division phase, and focal necrosis, but no 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 whether there was evidence 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.
②Taking 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 0.3 cm intervals 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 Appendix 1 for description records of general examination)
a. Tumor and cutting edge: tumor tissues were fully sampled, depending on the tumor size, infiltration depth, different textures and colors of the areas 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 may 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 tissues in standard fixative, and always maintain adequate amount of fixative and formaldehyde concentration to avoid drying of specimens or tissue decay due to insufficient amount of fixative or reduced concentration, so as to be ready to supplement the specimens according to the diagnostic needs of microscopic observation, or to review the bulk specimens or supplement the specimens 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 review is requested due to disagreement of external consultation, etc., the hospital can handle it by itself.
(4) Pathological types.
① The 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) Pathology report content.
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 invasive carcinoma: suggest 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 the 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 margins 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 margins are defined as tumor less than 1 mm from the cut margin or cancer cells visible at the electrodebrider cut margin.
C. The pathology report of the surgically resected specimen must include the following
a. Basic patient information and delivery information.
b. General situation: location of tumor, size, general type, depth of infiltration seen by the naked eye, distance between upper and lower cut edges and tumor.
c. Degree of tumor differentiation (tumor typing and grading).
d. Depth of tumor infiltration (T-stage, T-stage or pT is determined based on tumor cells with morphological basis. Mucus lake without cells within the specimen treated with neoadjuvant therapy is not considered as tumor residual) (see Annex 3 for TNM staging criteria).
e. Number of lymph nodes detected and the number of positive lymph nodes (N stage).
f. The status of the proximal cut margin and distal cut margin. If the tumor is close to the incisional margin, the distance between the tumor and the incisional margin should be measured and reported under the microscope, with positive incisional margin reported within 1 mm of the tumor from 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 complete a detailed pathological diagnosis request form, truthfully describing the surgical findings and relevant clinical ancillary tests and clearly marking the lymph nodes.
3. Laboratory tests.
(1) Blood tests: routine blood tests, blood biochemistry, serum tumor markers, etc.
(2) Urine, stool routine, fecal occult blood test.
4. Imaging examinations.
(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, 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 imaging (MRI): MRI examination is one of the important imaging examinations. MRI can help determine the status of peritoneal metastases and can be used as appropriate.
(3) Upper gastrointestinal imaging: It is helpful to determine the scope and functional status of the primary gastric lesion, especially gas-barium double contrast imaging is one of the common imaging methods to diagnose gastric cancer. Water-soluble contrast agent is recommended for patients suspected of pyloric obstruction.
(4) Chest X-ray examination: it should include frontal and lateral phases, which can be used to evaluate whether there are 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 the local lymph node metastasis and superficial metastasis 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: It is not recommended for routine use. Bone scan can be considered for patients with gastric cancer suspected of having bone metastasis.
IV. Differential diagnosis
(1) 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 and sarcoidosis.
(B) Other malignant tumors of the stomach: mainly distinguish 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
(1) 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 team (MDT) model should be adopted to apply surgery, chemotherapy, radiotherapy and biologic targeting in a planned and rational manner to achieve the goals of radical or maximum tumor control, prolonging the patient’s survival and improving the quality of life. The aim is to achieve radical or substantial tumor control, prolong patients’ survival and improve their quality of life.
For early stage gastric cancer without evidence of 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. Locally progressive gastric cancer or early gastric cancer with lymph node metastasis should be treated with a comprehensive treatment based on 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, while the best supportive treatment such as pain relief, stent placement and nutritional support should also be actively given.
(ii) Surgical treatment.
1. Principles of surgical treatment.
Surgical resection is the main treatment for gastric cancer and the only way to cure it. 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 for 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. Surgical style and indications.
(1) Reduction surgery.
The scope of resection is smaller than that of standard radical surgery.
(1) Endoscopic mucosa resection (EMR) and endoscopic submucosa dissection (ESD) indications: highly or moderately differentiated, non-ulcerated, less than 2 cm in diameter, no lymph node metastasis intra-mucosal cancer.
Gastric D1 resection indications: intra-mucosal carcinoma with a diameter of more than 2 cm, and gastric carcinoma 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 submucosal 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.
Table 1. Lymph node dissection scope of D1 and D2 (standard radical surgery) for gastric cancer at different sites
Distal gastrectomy
Proximal gastrectomy
Total gastrectomy
D1
1, 3, 4sb, 4d, 5, 6, 7
1, 2, 3, 4sa, 4sb, 7
1–7
D2
d1+8a, 9, 11p, 12a
D1+8a, 9, 10, 11
D1+8a, 9, 10, 11, 12a