I. Scope
This guideline formulates the diagnostic basis, diagnosis, differential diagnosis, treatment principles and treatment plan of gastric cancer (including esophagogastric junction cancer).
This guideline applies to the diagnosis and treatment of gastric cancer by municipal and county-level pilot hospitals with corresponding qualifications for standardized treatment of common tumors and their medical personnel.
II. Terms and Definitions
The following terms and definitions are applicable to this standard.
Early gastric cancer (EGC): It refers to gastric cancer whose lesions are confined to mucosa or submucosa, regardless of whether there are lymph node metastases or not. Under the naked eye, the general types are classified as elevated type (Type I), superficial type (Type II), sunken type (Type III) and mixed type.
Third, abbreviations
The following abbreviations apply to this standard.
CEA: (carcinoembryonic antigen) 癌胚胚抗原
IV. Diagnostic and treatment process (omitted)
V. Diagnostic basis
(I) Etiology.
The etiology of gastric cancer has not been elucidated so far, but it is recognized that several factors can influence and participate in the occurrence of gastric cancer. The possibility of association with the following factors is known to exist mainly: H. pylori infection; nitroso compounds; high salt nitrate intake; dicarbonyl compounds; fungi; heredity.
(ii) High risk factors.
Gender: men are 1.5 times more likely to develop gastric cancer than women;
Age: The incidence of gastric cancer increases significantly with age;
Diet: salted and cured vegetables or smoked meat and fish;
Smoking: Men who smoke die from stomach cancer twice as often as men who do not smoke;
Stomach surgery;
Pre-cancerous diseases: chronic atrophic gastritis, gastric ulcers, gastric polyps;
Family tumor diseases: including hereditary non-polyposis bowel cancer, hereditary diseases such as familial adenomatous polyps, etc;
Family history of gastric cancer;
Pernicious anemia: often combined with atrophic gastritis;
Obesity: men who are 20-25 kg over normal weight have higher risk of gastric cancer;
Economic status: The incidence of gastric cancer is higher in areas with poorer economy.
(C) Symptoms.
1.Time of onset: 10% of the time between onset and consultation is within 3 months, 10% is between 3 months and 2 years, and 20% is more than 2 years.
2. Main symptoms: usually not specific. There is almost no symptom in early stage of cancer, with wasting as the most common, followed by pain in the stomach area, loss of appetite, vomiting and so on. Most of the patients are already in advanced stage when first diagnosed. The first symptom of early gastric cancer can be upper abdominal discomfort (including epigastric pain, mostly occasional), or heart fossa distension, burning or mild spasmodic pain after full stomach, which can be relieved by itself; or loss of appetite and fullness after a short meal.
If the cancer occurs in cardia, there is choking sensation when eating; if it is located in pylorus, there is fullness and pain after eating; occasionally, there is vomiting blood or tarry stool because the cancer breaks out and bleeds, or diarrhea because of low gastric acid and fast gastric emptying, or the patient has a long history of dyspepsia, which causes some symptoms when gastric cancer occurs, but it is easy to be ignored. Few patients may be seen for upper abdominal mass or for wasting, weakness, gastric perforation or metastases.
(IV) Physical signs.
1.Early gastric cancer may not have any physical signs.
Among the signs of middle and late stage gastric cancer, upper abdominal pressure pain is most common. 1/3 patients can find nodular masses, which are firm and moving, mostly located in the right side of abdomen equivalent to gastric sinus, with pressure pain. The tumor of gastric body can sometimes be palpated, but it cannot be found in the cardia.
3.Metastatic signs: metastasis to the liver can make it enlarged and firm nodules can be found, ascites can occur when there is metastasis to the peritoneum, and mobile turbid sounds can appear. Virchow lymph nodes can be felt when there is distant lymph node metastasis, which are hard and immobile. On anal examination, a mass can be felt in the interrectal bladder recess. In case of Krukenberg’s tumor, enlarged ovaries on both sides can be detected on vaginal examination.
4, with cancer syndrome: including recurrent thrombophlebitis (Trousseau’s sign), acanthosis nigricans (pigmentation in the skin folds, especially in the two axillae), dermatomyositis, membranous nephropathy, microangiopathic hemolytic anemia, etc.
(E) Auxiliary examinations.
1.Conventional examination
(1) Blood examination: anemia is common, about 50% have iron deficiency anemia, which is caused by long-term blood loss; or caused by nutritional deficiency, such as combined with pernicious anemia, then see megaloblastic anemia; blood sedimentation is increased.
(2) Gastric fluid examination: about 40% to 60% of patients have no free acid in the stomach and positive lactic acid test; lactobacillus, octococcus and yeast in gastric fluid residue; cancer cells can be found in gastric fluid when cancer tissue is ulcerated and necrotic.
(3) Fecal occult blood test: Fecal occult blood test is often consistently positive, which is convenient to detect and has the significance of auxiliary diagnosis. It can be used as the first choice of gastric cancer screening test.
2.Tumor marker test
Currently, the main clinically used gastric cancer markers are CEA, CA19-9, etc., but their specificity is not strong, so combined testing can increase their sensitivity and specificity.
(1) CEA: carcinoembryonic antigen, a polysaccharide-rich protein complex, is a carcinoembryonic antigen produced in embryonic and fetal stages, which is significant for the prognosis of gastric cancer, and is related to progressive hypodifferentiated adenocarcinoma, as well as tumor size, plasma surface infiltration and lymph node metastasis. If CEA level decreases >50% or drops to normal range and lasts for more than 4 weeks, it can be used as an effective indicator of treatment; if it continues to increase after treatment, it indicates poor prognosis.
(2) CA19-9 (optional): It is a kind of large molecule glycoprotein containing mucus, which is related to tumor size, lymph node metastasis and depth of infiltration, and is an independent indicator to determine the prognosis of gastric cancer patients.
3.Imaging examination
(1) Personnel
Personnel engaged in GI imaging, ultrasound, CT and MRI should receive systematic training in the hospital or higher hospitals in order to be qualified to issue independent diagnostic reports, and it is recommended that the training time for each examination should be at least 3-6 months. Practitioners should be trained in “radiation protection knowledge” and pass the “large equipment induction qualification” examination in accordance with the relevant national regulations.
(2) Equipment and site
All equipment and sites should meet the national “radiation protection” requirements.
(3) Basic examination techniques and diagnosis
① Chest X-ray examination: both frontal and lateral chest films must be taken to exclude the presence of pulmonary metastases, and CT chest examination can be used in accordance with the patient’s economic conditions for lesions found on chest films that are difficult to characterize.
(ii) Upper gastrointestinal tract imaging: it can be the first choice of routine examination for the diagnosis of gastric cancer, which can help to observe the extent of tumor infiltration in the gastric cavity, the location of the mass, the degree of gastric cavity narrowing, the presence of pyloric obstruction, etc. It can also help to differentiate from gastric inflammatory lesions, gastric wall in sexual lesions and gastric lymphoma by observing the morphology of gastric mucosa and the softness of gastric wall, etc.
Ultrasound examination: Ultrasound examination is simple, easy and inexpensive, and can be used as a routine examination for patients with gastric cancer, mainly for detecting metastasis of important organs and lymph nodes in abdominopelvic cavity, and also for examination of supraclavicular and cervical lymph nodes. For hospitals with conditions, ultrasound-guided liver and lymph node aspiration biopsy can also be carried out, which is beneficial to tumor diagnosis and staging.
④CT examination: CT examination has been widely used in clinical practice, which is helpful to observe the infiltration depth of stomach tumor to stomach wall, the relationship with surrounding organs, and the presence of lymph node metastasis and distant metastasis (such as liver, ovary, peritoneum, omentum, etc.). For larger stomach tumors, CT examination of abdomen and pelvis is recommended to understand whether there are metastases in the pelvis, especially for female patients, to observe whether there are ovarian metastases. For patients without CT contrast allergy, in principle, enhanced CT scan should be performed, which can help to detect micro metastases.
⑤ MRI examination (optional): Due to factors such as equipment, scanning technology and examination cost, MRI examination is not yet a routine examination for patients with gastric cancer, but for patients with liver metastases suspected by ultrasound or CT examination, MRI can help to make a clear diagnosis.
(6) Bone scan (optional): it helps to diagnose bone metastasis and is reasonably selected according to clinical needs.
(⑦All kinds of examination and diagnosis reports should reflect the international TNM staging concept.
4.Lumpectomy examination
(1) Endoscopic examination: it is one of the most important means in the diagnosis of gastric cancer and plays an important role in the qualitative and localized diagnosis of gastric cancer and the selection of surgical plan. It is a necessary routine examination for patients who are to undergo surgical treatment. In addition, adequate preparation is necessary before endoscopy, and it is recommended to apply debulking and demucosal agents, carefully observe all parts, collect pictures, apply staining and magnification techniques to suspicious parts for further observation, and perform indicative biopsy, which is the key to improve the detection rate of early gastric cancer. Improving the detection rate of gastric cancer is one of the important means to reduce the mortality rate of gastric cancer at this stage.
(2) Pigmented endoscopy (optional): After the completion of conventional endoscopy, it is recommended that indigo carmine staining should be routinely performed on subjects with clinical suspicion of early gastric cancer, high-risk groups, and those aged >40 years old to improve the detection rate of early gastric cancer. Attention should be paid to cleaning the mucus on the surface of gastric mucosa before staining, and spraying should be done to make the stain spread evenly on the gastric mucosa as much as possible, and observation should be performed after rinsing.
(3) Magnification endoscopy (optional): Magnification endoscopy directly observes the surface morphology of gastric mucosa, and can accurately identify the benign and malignant lesions according to the shape of gastric hollows and surface vascular morphology, which is more effective when used in combination with stain.
(4) Ultrasonic endoscopy (optional): It can not only directly observe the lesion itself, but also detect the depth of tumor infiltration and perigastric enlarged lymph nodes through ultrasonic probe, which is a more reliable preoperative staging method for gastric cancer and helps to diagnose, clinically stage and formulate the best surgical plan for gastric cancer.
5.Cytological examination
(1) Endoscopic cytological examination: under the direct vision of fiberscope, cells are collected by three methods: rinsing, scrubbing and blotting, and the positive rate is higher; or the stomach wall is repeatedly rinsed with buffer solution by inserting a gastric tube, and then the buffer solution is collected and smear is made after sedimentation for cytological examination, and the positive rate of both cytological examinations can reach over 90%.
(2) Ascitic fluid cytology or intraoperative peritoneal flushing or lavage cytology: it can clarify whether there are free cancer cells in the abdominal cavity (FCC), which is important for guiding clinical staging.
(3) Puncture cytology: for clear diagnosis of supraclavicular lymph node metastasis.
Classification and staging of gastric cancer
(1) Classification of gastric cancer.
Histological classification of gastric tumor (WHO, 2000)
Epithelial tumor
Intraepithelial tumor-adenoma 8140/0
Carcinoma
Adenocarcinoma 8140/3
Intestinal type 8144/3
Diffuse type 8145/3
Papillary adenocarcinoma 8260/3
Tubular adenocarcinoma 8211/3
Mucinous adenocarcinoma 8480/3
Indolent cell carcinoma 8490/3
Adenosquamous carcinoma 8569/3
Squamous cell carcinoma 8070/3
Small cell carcinoma 8041/3
Undifferentiated carcinoma 8020/3
Other
Carcinoid tumor (highly differentiated neuroendocrine tumor) 8240/3
Non-epithelial tumors
Smooth muscle tumor 8890/0
Nerve sheath tumor 9560/0
Granulosa cell tumor 9580/0
Angiosarcoma 8711/0
Smooth muscle sarcoma 8890/3
Mesenchymal tumor of gastrointestinal tract 8936/1
Benign 8936/0
Uncertain malignant potential 8936/1
Malignant 8936/3
Kaposi’s sarcoma 9140/3
Other
Malignant lymphoma
Marginal zone B-cell lymphoma, MALT type 9699/3
Lymphoma of the set of cells 9673/0
Diffuse large B-cell lymphoma 9680/3
Other
Secondary tumors
(B) Staging of gastric cancer.
So far, the staging of gastric cancer is still not completely consistent, and the more commonly used are the American staging system (AJCC), the Japanese staging system of gastric cancer and the United Cancer Society International. Among them, the TNM system of the United Cancer Society International is the most commonly used. At present, the latest gastric cancer staging system adopts the 2002 International Staging of Gastric Cancer published by the International Union Against Cancer (UICC).
UICC TNM Definition and Staging (2002, 6th edition)
Primary tumor(T)
TX
Primary tumor cannot be assessed
T0
No evidence of primary tumor
Tis
Carcinoma in situ: intraepithelial carcinoma not infiltrating the lamina propria
T1
Tumor invades the lamina propria or submucosa
T2
Tumor invades the muscularis or subplasma layer1
T2a
Tumor invasion to the muscular layer
T2b
Tumor invading subplasma layer
T3
Tumor penetrated the plasma membrane (dirty peritoneum)1 without invading adjacent structures2,3
T4
Tumor invaded adjacent structures2,3
Note: 1. The tumor penetrates the muscular layer and enters the gastrocolic or hepatogastric ligament, or enters the greater or lesser omentum, but does not penetrate the visceral peritoneum covering these structures, in this case the tumor is T2, if it penetrates the visceral peritoneum of these structures the tumor is T3.
The adjacent structures of the stomach include the spleen, transverse colon, liver, septum, pancreas, abdominal wall, adrenal glands, kidney, small intestine and retroperitoneum.
3. The tumor extends from the stomach wall to the duodenum or esophagus, and the depth of the most severe infiltration, including the stomach, determines T.
Regional lymph nodes (N)
NX
Regional lymph node metastasis cannot be assessed
N0
No regional lymph node metastasis1
N1
With 1 to 6 regional lymph node metastases
N2
With 7 to 15 regional lymph node metastases
N3
Greater than 15 regional lymph node metastases
Note: 1 Regardless of the total number of lymph nodes resected and examined, if all lymph nodes were free of metastasis, it was designated as pN0.
Distant metastasis (M)
MX
Distant metastasis could not be assessed
M0
No distant metastasis
M1
With distant metastasis
UICC TNM stage of gastric cancer
Stage 0
Tis
N0
M0
Stage IA
T1
N0
M0
IB period
T1
N1
M0
T2 a/b
N0
M0
Phase II
T1
N2
M0
T2 a/b
N1
M0
T3
N0
M0
Phase IIIA
T2a/b
N2
M0
T3
N1
M0
T4
N0
M0
Stage IIIB.
T3
N2
M0
Phase IV.
T4
N1~3
M0
T1～3
N3
M0
Any T
Any N
M1
VII. Diagnosis
(A) Clinical diagnosis.
1. Early stage may have no symptoms and signs, or epigastric pain, fullness and discomfort, loss of appetite; or the symptoms of the original gastric ulcer are aggravated, abdominal pain is persistent or lost rhythmically, and the symptoms are not relieved by treatment of ulcer disease. Vomiting blood, black stool may appear.
2.Late stage weight loss, progressive anemia, low fever, palpable mass in upper abdomen with pressure pain, enlarged left supraclavicular lymph node, ascites and cachexia.
3.Cancer of cardia invades esophagus, which may cause difficulty in swallowing. Pyloric cancer may show symptoms and signs of pyloric obstruction.
4.Laboratory examination Early suspected gastric cancer, low free gastric acid or lack of it, such as decreased red blood cell pressure, hemoglobin, red blood cells, fecal occult blood (+). Abnormal increase of tumor markers.
5. Imaging tests suggesting gastric cancer (gastric double contrast angiography, CT)
(II) Confirmation of diagnosis.
Diagnosis mainly relies on gastroscopic biopsy histological pathology diagnosis. If a city, county or regional hospital is available, immunohistochemical examination should be performed to identify the histological typing of the tumor or determine the neuroendocrine status of the tumor. Recently, more clinical attention has been paid to the preoperative staging of gastric cancer, and reasonable treatment plans are formulated according to the preoperative staging. Endoscopic ultrasound, CT, laparoscopy, etc. can be effective means of preoperative staging.
(C) Differential diagnosis.
1. Differentiation from benign diseases of the stomach
(1) Gastric ulcer: Gastric cancer has no characteristic symptoms and signs, especially in young people it is often misdiagnosed as gastric ulcer or chronic gastritis. Certain typical X-ray manifestations of gastric ulcer can be used as diagnostic basis, such as niche shadow generally protrudes outside the lumen, with diameter within 2cm, its mouth is smooth and neat, the surrounding mucosa is radial, and the gastric wall is soft and expandable, etc.; while the niche shadow of progressive ulcerative carcinoma is larger and located in the lumen, often accompanied by finger indentation and fissure destruction, local gastric wall is stiff and the gastric lumen is poorly expandable, etc. However, some callus ulcers are easily confused with ulcerative carcinoma, which needs further gastroscopic biopsy to differentiate.
(2) Gastric polyp (gastric adenoma or adenomatous polyp): benign tumors derived from gastric mucosal epithelium can occur at any age, but they are more common between 60 and 70 years old. Smaller adenomas may be asymptomatic, while larger ones may cause upper abdominal fullness and discomfort, vague pain and nausea. Barium X-ray examination shows a round filling defect with a diameter of about 1 cm and complete border. Gastric adenoma is often confused with augmented early gastric cancer, and gastroscopic biopsy is recommended to confirm the diagnosis.
(3) Gastric smooth muscle tumor: It can occur at any age, mostly under 50 years old. Patients often have epigastric fullness, vague pain or distension, and intermittent vomiting of blood or black stool when the tumor increases and forms ulcers. Gastroscopy can be distinguished from gastric cancer, but it is difficult to decide whether it is smooth muscle tumor or smooth muscle sarcoma.
(4) Gastric giant crepitus: similar to infiltrating gastric cancer, it usually occurs in the upper part of the stomach. X-ray examination of benign giant crepitations shows that the gastric mucosa is ring-shaped or curved, while the mucosa of infiltrating gastric cancer is mostly thickened in a straight line. In addition, giant crepitus is often accompanied by hypoproteinemia, while infiltrating gastric cancer can be seen as malignant.
(5) Hypertrophic sinusitis: it is mostly caused by H. pylori infection, which can cause narrowing of gastric sinus, loss of peristalsis and stretching of gastric wall; infiltrating gastric cancer has flat or granular deformation of mucosa, rigid gastric wall and hypotonic contrast, and there is a big difference between the two.
(6) Warty gastritis: it occurs mostly in young people, often combined with duodenal ulcer, and is better differentiated from gastric cancer.
(7) Gastric mucosal prolapse: Gastric mucosal prolapse is caused by the abnormal relaxation of the gastric mucosa retrograde into the esophagus or prolapse into the duodenal bulb. The diagnosis can be confirmed by x-ray barium meal examination. The abdominal pain is periodic and rhythmic, which is easier to distinguish by gastroscopy.
2.Differentiate from other malignant tumors of the stomach
(1) Primary malignant lymphoma: 0.5%-8% of malignant tumors of the stomach. It is mostly seen in young and strong people, and is usually found in the gastric sinus, anterior pylorus area and gastric lesser curvature. The lesion originates from the lymphoid tissue in the submucosa and can extend to the surrounding area and involve the whole layer of the gastric wall, and the plasma membrane or mucosa of the lesion is often intact. When the lesion infiltrates 40% to 80% of the mucosa, ulcers of varying sizes and depths occur.
The clinical manifestations include epigastric fullness, pain, nausea, vomiting, black stool, decreased appetite, emaciation, weakness, anemia and other non-specific symptoms. The characteristic changes are irregular thickening of diffuse gastric mucosal folds, irregularly patterned multiple ulcers, thickening of mucosal elevation at the edge of ulcers to form large folds; single or multiple round filling defects with “pebble-like” changes.
(2) Gastric sarcoma: 0.25%-3% of gastric malignant tumors, 20% of gastric sarcomas, mostly seen in the elderly, preferably in the fundus and body of the stomach. The tumor is usually large, often above 10 cm, spherical or hemispherical, and the central part of the tumor often forms ulcers due to insufficient blood supply. Clinical manifestations mainly include pain, discomfort, nausea, vomiting, loss of appetite, emaciation, fever and upper gastrointestinal bleeding in the upper abdomen, and most patients can find a mass in the abdomen due to the huge tumor and local pressure pain.
The submucosal type of gastric smooth muscle sarcoma can be seen on barium X-ray examination, with a spherical filling defect with neat edges in the gastric cavity and a typical “umbilical-like” niche in the center, while the subplasma type can only be seen as compression and pushing of the gastric wall. During gastroscopy, the surface mucosa of submucosal smooth muscle sarcoma is translucent, and the surrounding mucosa may be “bridge-shaped” creases; when the tumor infiltrates into the gastric wall, its boundary is unclear, ulcers and thick mucosal creases are visible, and the gastric wall is stiff, which is generally not difficult to distinguish from gastric cancer.
In addition, gastric cancer should be distinguished from gastric mucosal prolapse, gastric carcinoid tumor, fundic venous tumor, pseudolymphoma, foreign body granuloma and other lesions. When a mass is felt in the upper abdomen, it should be distinguished from transverse colon or pancreatic masses, and those with liver metastases should be distinguished from primary liver cancer, and the differential diagnosis is mainly made by X-ray, barium meal imaging, gastroscopy and biopsy.
VIII. Treatment
(I) Treatment principles.
Clinically, the principle of comprehensive treatment should be adopted. In other words, according to the patient’s physical condition, pathological type, invasion range (stage) and development trend of the tumor, the existing treatment means should be applied in a planned and reasonable way, in order to eradicate and control the tumor and increase the cure rate and improve the quality of life of the patient. For patients to be treated with radiotherapy and chemotherapy, Karnofsky or ECOG score should be done (see Appendix C).
The treatment of gastric cancer is mainly divided into surgery, radiotherapy and chemotherapy and their related treatments.
(II) Surgical treatment.
1. Principles of surgical treatment
Surgical resection is the main treatment for gastric cancer and the only way to cure gastric cancer at present. The complete resection of the lesion and the 5cm margin of the gastric section, 3-4 cm of the first segment of the duodenum should be resected for the distal part of the cancer, and 3-4 cm of the lower end of the esophagus should be resected for the proximal part of the cancer, which has been recognized by most scholars. Nowadays, the range of lymph node clearance is often indicated by D. For example, D1 surgery refers to the clearance of lymph nodes up to station 1, or D0 surgery if the requirement of lymph node clearance at station 1 is not met, and D2 surgery refers to the complete clearance of lymph nodes at station 2.
For distal gastric cancer, subtotal gastrectomy has fewer complications than total gastrectomy; for proximal gastric cancer, major proximal gastrectomy can be considered if the tumor is early; for most progressive gastric cancer, total gastrectomy is appropriate because of the need for D2 clearance.
Recently, with the emphasis on postoperative quality of life and the development of minimally invasive surgery and laparoscopy, many hospitals have carried out various procedures to reduce the scope of surgery under the premise of ensuring radical treatment.
In the case of palliative surgery, if the tumor cannot be completely removed, the goal of treatment is to resolve the problems, symptoms, and comorbidities caused by the presence of cancer cells, such as in the case of gastric cancer where the lesion cannot be completely removed, surgery is performed to reduce the bleeding caused by ulceration of the gastric cancer lesion or to resolve the obstruction of the digestive tract caused by the tumor. In this case, the aim of medical treatment is to reduce the size of the tumor, slow down its growth, prevent its spread, and thereby prolong life. Reduced surgery, such as gastrostomy and gastro-jejunostomy, is performed to ensure the patency of the digestive tract and improve nutrition.
2.Surgical treatment mode
(1) Principles
① Resectable tumors.
Endoscopic mucosal resection should be considered for stage T1 tumors confined to the lamina propria (hospitals with conditions for implementation can consider carrying out);
T1~T3: Adequate stomach should be resected and ensure negative microscopic margins;
T4 tumor should be resected in its entirety;
Gastrectomy should include regional lymph node dissection (D1), and D2 is recommended, with at least 15 or more lymph nodes removed;
Splenectomy is not necessary for routine or prophylactic splenectomy, but may be considered when the spleen or splenic hilum is involved;
Some patients may be considered for placement of a jejunal nutrient tube (especially when postoperative radiotherapy is recommended).
(ii) Unresectable tumors.
Part of the stomach can be resected, even if the margins are positive;
Lymph node dissection is not required;
Short-circuit surgery helps to relieve the symptoms of obstruction;
Gastrostomy and placement of jejunal nutrition tube.
(iii) Criteria for inoperable cure.
Imaging confirmation or high suspicion or biopsy confirmed metastasis in more than N3 lymph nodes;
Tumor invasion or encirclement of large blood vessels;
Distant metastasis or peritoneal implantation;
Positive cytological examination of ascites.
(2) Surgical treatment mode (indications)
①Stage IA T1
Suitable for submucosal endoscopic resection or modified radical gastric cancer resection (MGA, MGB). Submucosal endoscopic resection is suitable for small mucosal layer gastric cancer without lymph node metastasis. 2cm is the upper limit of endoscopic mucosal whole block resection, so the depth of gastric cancer infiltration, histological type and tumor size must be accurately determined before surgery.
②Stage IB (T1~T2)
Standard radical gastric cancer resection for stage IB gastric cancer. If the diameter of T1N1 tumor is less than 2cm, it is suitable for modified B gastric cancer radical surgery. T1N1 diameter more than 2.1cm or T2N0 gastric cancer should receive standard gastric cancer radical surgery.
③ Stage II (T1N2, T2N1, T3N0)
Stage II gastric cancer requires standard radical gastric cancer surgery regardless of T and N status. Adjuvant chemotherapy is recommended, but there is no accepted chemotherapy regimen, and clinical studies are needed to determine the standard adjuvant treatment regimen.
④Stage IIIA (T2N2, T3N1, T4N0)
Stage III gastric cancer requires standard or expanded radical gastric cancer surgery according to the status of T and N
Clinical studies of adjuvant chemotherapy and neoadjuvant chemotherapy are recommended. for stage T4 gastric cancer, combined resection of the involved organs and/or adjuvant radiotherapy can be considered, as the prognosis of patients with sarcoid residuals (R1) is significantly worse than those without residuals.
⑤ Stage IIIB (T3N2, T4N1)
T3N2 can be treated with standard radical surgery, although the survival value of D3 surgery for N2 gastric cancer is unclear, and the procedure is routinely used in Japan.
Combined organ resection is recommended to obtain R0 resection for T4 gastric cancer. Randomized controlled studies of adjuvant chemotherapy, neoadjuvant chemotherapy, and adjuvant radiotherapy may be performed.
Stage IV (N3, CY1, M1)
Most stage IV gastric cancers are not curable by surgery alone, unless N3 or T4N2 gastric cancer. If only N3 determines the patient’s stage IV, D3 surgery is feasible to achieve R0 resection.
For M1 gastric cancer, palliative surgery (resection, short-circuiting, stoma surgery) may be considered if the patient is in good general condition and has tumor emergencies such as bleeding, obstruction, and malnutrition with chemotherapy, radiotherapy, or best supportive care (tumor-reducing surgery). There is no evidence that the above treatment options can prolong survival in stage IV gastric cancer, but it is possible to prolong survival, shrink lesions, and relieve symptoms. The end point of treatment for patients with advanced gastric cancer is to improve the quality of life.
(3) Contraindications to surgery
(1) Deterioration of general condition that cannot tolerate surgery.
(ii) Local infiltration is too extensive to be removed.
③Conclusive evidence of distant metastasis, including multiple lymph node metastasis, extensive peritoneal dissemination and multifocal (3 or more) metastasis in the liver, etc.
(4) There are obvious defects in heart, lung, liver, kidney and other important organ functions, severe hypoproteinemia, anemia and malnutrition that cannot tolerate surgery.
4.Surgical complications
(1) Early complications after gastrectomy
① Bleeding
Bleeding in the gastric cavity;
Intra-abdominal bleeding.
(2) Stump fistula or anastomotic fistula
Duodenal stump fistula;
Gastroduodenal anastomotic fistula ;
Gastrojejunostomy fistula.
(iii) Obstruction
Anastomotic obstruction;
Acute input loop obstruction.
④ Postoperative gastric emptying disorder
⑤ Hepatobiliary-pancreatic comorbidities
Postoperative pancreatitis ;
Postoperative jaundice ;
Bile duct or pancreatic duct injury.
(2) Long-term complications after gastrectomy
① Mechanical obstruction
Chronic input loop obstruction ;
Chronic output loop obstruction and internal hernia after partial gastrectomy of Bi-II type;
jejuno-gastric sleeve;
Posterior gastroduodenal obstruction.
②Pathophysiological disorders
General physiological disorders leading to chronic dyspepsia;
Alkaline reflux gastritis;
Early dumping syndrome;
Posterior dumping syndrome ;
Roux retention syndrome (Roux stasis syndrome);
Specific absorption disorders and malnutrition.
(iii) Anemia and metabolic diseases
Hypochromic microcytic anemia due to iron deficiency;
VitB12 deficiency is often combined with macrocytic anemia;
Metabolic bone disease.
④Other complications
Small gastric remnant;
Fecal stone formation ;
Stomach remnant cancer.
(C) Radiotherapy (refer to higher level hospital if radiotherapy condition is not available).
Radiotherapy is mainly used for postoperative adjuvant treatment of operable gastric cancer, comprehensive treatment of inoperable locally advanced gastric cancer, and palliative reduction treatment of advanced gastric cancer.
1.Principles
(1) Adopt synchronized radiotherapy based on 5-fluorouracil;
(2) Postoperative chemoradiotherapy should be given to T2b, T3, T4 or N+ cases without distant metastasis after radical resection of gastric cancer;
(3) For non-radical resection with residual cases, postoperative chemoradiotherapy should be given regardless of the stage of disease;
(4) For locally advanced inoperable gastric cancer without distant metastasis, if the patient’s general condition allows, synchronized chemoradiotherapy should be given in the hope of obtaining a chance of operable resection or long-term control;
(5) When inoperable advanced gastric cancer with vomiting blood, blood in stool, dysphagia, abdominal pain, pain caused by metastases in bone or other parts of the body, which seriously affects the patient’s quality of life, synchronized chemoradiotherapy or radiotherapy alone can play a good role in palliation and disease reduction if the patient’s physical condition allows it;
(6) Radiotherapy using conventional radiotherapy techniques;
(7) Postoperative adjuvant therapy cases are carried out 4 weeks after surgery and after the body basically recovers.
2.Stage treatment mode of gastric cancer.
(1)When stage I tumor invades the muscle layer or has regional lymph node metastasis (T1N1M0, T2bN0M0), postoperative synchronized chemoradiotherapy is recommended;
(2) Stage II (T1N2M0, T2a/bN1M0, T3N0M0), postoperative chemoradiotherapy is recommended;
(3) Stage III (T2a/b-T3N2M0, T3N1M0, T4N0M0), postoperative chemoradiotherapy is recommended, and preoperative chemoradiotherapy can also be considered;
(4) Stage IV (T4N1-3M0, T1-3N3M0), postoperative synchronized chemoradiotherapy is recommended, and preoperative synchronized chemoradiotherapy can also be considered;
(5) Locally advanced inoperable resectable gastric cancer (T4NxM0), if the patient’s general condition allows, synchronized chemoradiotherapy is recommended;
(6) If there is tumor residual after surgery, it is recommended to synchronize chemoradiation therapy after surgery for all stages;
(7) When inoperable advanced gastric cancer (TxNxM1) presents with vomiting blood, blood in stool, dysphagia, abdominal pain, pain caused by bone or other metastases, which seriously affects the patient’s quality of life, synchronized chemoradiotherapy or radiotherapy alone can be considered to achieve palliative reduction treatment if the patient’s physical condition allows;
(8) In cases of local recurrence after surgery, if the patient cannot be operated again and has not received radiotherapy, and if the patient’s physical condition allows, synchronous chemoradiotherapy can be considered, and the efficacy of chemoradiotherapy can be evaluated 4 weeks after chemoradiotherapy in the expectation of striving for surgery again.
3.Effect of treatment
The evaluation of the efficacy of radiotherapy is based on the WHO criteria for evaluating the efficacy of solid tumors or RECIST (see Appendix D).
4.Protection
Using conventional radiotherapy techniques, attention should be paid to the protection of the organs around the stomach, especially the intestine, in order to avoid serious radiation damage to them.
5.Three-dimensional conformal radiotherapy technique (3DCRT) and intensity-modulated radiotherapy technique (IMRT) are the more advanced radiotherapy techniques at present. If the hospital has this condition, it can be used for gastric cancer patients, and CT or PET/CT is used for the design of radiotherapy plan.
(iv) Chemotherapy.
Gastric cancer chemotherapy is divided into neoadjuvant chemotherapy (preoperative), adjuvant chemotherapy (postoperative), palliative chemotherapy, local chemotherapy and chemotherapy for sensitization.
1.Principles
(1) Clinical indications must be mastered;
(2) The standardization and individualization of treatment protocols must be emphasized;
(3) The chosen program and the drugs used can be implemented according to the specific medical conditions of the local hospital with reference to the norms.
2.Efficacy evaluation
The efficacy evaluation of chemotherapy treatment should refer to the WHO efficacy evaluation standards for solid tumors or RECIST efficacy evaluation standards (see Appendix).
3.Commonly used regimen
Commonly used chemotherapy drugs for gastric cancer: 5-fluorouracil, cisplatin, etoposide, adriamycin, epi-amycin, mitomycin, methotrexate, etc.
Commonly used chemotherapy regimens.
CF regimen (cisplatin/5FU)
ECF regimen (epi-adriamycin/cisplatin/5-FU) and its modifications (oxaliplatin instead of cisplatin and/or capecitabine instead of 5FU)
ELF regimen (etoposide/calcium folinic acid/5-FU)
FAM regimen (5FU/adriamycin/mithramycin)
There is no definite second-line treatment option for gastric cancer.
(E) Integrated multidisciplinary treatment model.
1.Initial treatment
(1) Surgical resection is recommended for patients with stage T1 gastric cancer or those with active bleeding whose tumors are resectable if their physical conditions allow. Perioperative (preoperative and postoperative) chemotherapy is performed for patients with stage T2 or more advanced (clinical stage or positive lymph nodes). In medical institutions where multidisciplinary treatment is not possible, surgical resection may be preferred, and postoperative chemoradiotherapy may be performed in appropriate cases according to pathological findings;
(2) For limited-stage gastric cancer whose tumor cannot be resected when physical conditions allow, radiotherapy (45-50.4 GY) + concurrent administration of fluorouracil-based radiotherapy sensitizers in combination is recommended. Palliative chemotherapy can also be administered to these patients;
(3) For patients with limited stage gastric cancer in poor physical condition, the following options can be chosen: (i) radiotherapy (45-50.4GY) + concurrent fluorouracil-based radiotherapy sensitizer; or (ii) palliative chemotherapy;
(4) For locally unresectable tumors, preoperative chemoradiotherapy (5-FU/formyltetrahydrofolate, or a fluorouracil-based regimen, or a cisplatin-based regimen) is recommended.
2.Adjuvant therapy
(1) For patients with postoperative pathological stage T1N0M0 and T2N0M0, postoperative adjuvant therapy is not available, but for patients with high-risk factors (tumor hypofractionation or high histological grade, lymphovascular infiltration, neural infiltration or age less than 50 years), they should receive adjuvant chemoradiotherapy after surgery.
(2) For patients with T3 or T4 stage or any T with lymph node metastasis who achieve R0 resection after surgery, they should receive postoperative radiotherapy (45-50.4 GY) + concurrent fluorouracil-based radiotherapy sensitizers.
(3) Patients with gastric cancer who obtained R1 resection should receive radiotherapy (45-50.4GY) + concurrent fluorouracil-based radiotherapy sensitizers. If there is no distant metastasis, patients with R2 resection should choose the following treatments: (1) radiotherapy (45-50.4GY) + concurrent fluorouracil-based radiotherapy sensitizer; (2) palliative chemotherapy; or (3) best supportive care if the patient’s physical condition is very poor.
(4) For resected gastric cancer, the recommended postoperative combination chemoradiotherapy regimen is 5FU/formyltetrahydrofolate or capecitabine. Continuation of ECF regimen postoperatively should be considered only if ECF regimen has been used preoperatively (clinical stage T2 or more advanced tumor or positive lymph nodes).
(5) Patients in poor health, or patients in good health but with unresectable tumors, should have their tumors restaged after completion of all treatment or primary therapy. If it is determined that the tumor has achieved complete remission, the patient may be placed under observation. If conditions are suitable, surgical resection is possible. If there is residual tumor or evidence of distant metastasis, patients can undergo palliative treatment.
3.Palliative treatment
Palliative treatment includes best supportive care, chemotherapy and participation in clinical trials.
(VI) Other treatments.
1, intraoperative intraperitoneal warm perfusion chemotherapy (IPHC)
(1) Indications for IPHC: For patients with peritoneal invasion, positive abdominal lymph nodes, especially those with infiltration depth greater than S3, invasion area greater than 20cm2, poorly differentiated tumor tissue type, infiltrative growth, and positive abdominal washout cytology.
(2) Method: IPHC uses the synergistic effect of warmth and regional chemotherapy to directly kill free cancer cells and small peritoneal metastases in the abdominal cavity.
Due to the existence of “peritoneal-blood barrier”, large molecule water-soluble chemotherapeutic drugs can reach tens of times the concentration of blood in the peritoneal cavity, while reducing systemic toxic side effects; the physical warm effect of 42-43℃ can cause tumor tissue hypoxia and change the membrane permeability of tumor cells, thus promoting their uptake of chemotherapeutic drugs and interfering with the DNA synthesis of tumor cells. Animal experiments and clinical studies have shown that IPHC is clinically feasible, safe and reliable, convenient for anesthesia monitoring, and has little interference with physiology.
(3) Drugs: 5-Fu, cisplatin and oxaliplatin can be chosen.
2.Cancerous ascites.
In advanced gastric cancer with peritoneal metastasis and ascites, the local concentration of anti-cancer drugs injected into the peritoneal cavity is greater than the plasma concentration, which is more than 20 times, because of the light systemic reaction and strong local anti-cancer effect, the drugs can be reserved for intubation or peritoneal puncture injection during surgery. 2~3 kinds of combined drugs can be used to control ascites, and biological response modifiers such as mushroom polysaccharide and interleukin-II can be used once a week with diuretic application.
3.Treatment of liver metastasis of gastric cancer.
According to the patient’s general condition, hepatic artery infusion chemotherapy and chemoembolization (TACE) can be applied when the efficacy of systemic intravenous chemotherapy is not obvious or when liver metastasis progresses during chemotherapy. Isolated metastases can also be surgically removed and treated with local injection of anhydrous ethanol.
IX. Prognosis
The 5-year survival rate of gastric cancer after radical surgery depends on the depth of invasion of gastric wall, the extent of lymph node involvement and tumor growth pattern. The 5-year survival rate of gastric cancer is about 20%. If early gastric cancer involves only the mucosal layer, the prognosis is good, and the 5-year survival rate can be more than 95% after surgery.
If the tumor appears as a mass, the resection rate is high and the prognosis is better than that of the diffuse type with early metastasis. The prognosis of leathery stomach is very poor. If the tumor has invaded the muscular layer but no lymph node metastasis is found at the time of surgery, the 5-year survival rate can still reach 60-70%; if the tumor has reached the plasma layer and local lymph node metastasis, the prognosis is poor, and the 5-year survival rate is only 20% on average after surgery; in cases with distant dissemination, the 5-year survival rate is 0.
X. Follow up
After adjuvant chemotherapy for gastric cancer, a comprehensive review should be conducted every 3~4 months within 2 years, including physical examination, detection of tumor-related markers (CEA, CA19-9, etc.), X-ray and ultrasound, etc. A comprehensive review should be conducted every 6 months within 5 years.
XI. Prevention and screening
In the strategy of gastric cancer prevention and treatment, the selection of pathogenetic prevention and treatment and the adoption of effective screening methods are the keys to early detection, early diagnosis and early treatment of gastric cancer patients.
People with the following factors should be designated as high-risk groups for early or regular screening.
1.Patients over 40 years old, especially men, who have recently developed dyspepsia or suddenly developed vomiting blood or black feces;
2. Those who are to be diagnosed with benign ulcer and lack of gastric acid; chronic atrophic gastritis, especially type A, with intestinalization and atypical hyperplasia;
3, gastric ulcer after two months of treatment is ineffective, X-ray examination shows that the ulcer instead of increasing, gastroscopy should be performed immediately;
4.Persons with chronic abdominal distension, heartburn, acid reflux, nausea and vomiting, early satiety, belching, burping, progressive wasting, etc;
5, with symptoms of vomiting blood and black stool;
6.History of stomach disease;
7.Patients with cancer in the upper gastrointestinal tract in the family (those who have already suffered from cancer are not eligible for examination);
8.Frequent smoking, alcohol consumption, frequent consumption of moldy and pickled food;
9, X-ray examination of gastric polyps greater than 2cm, gastroscopy should be done;
10. More than 15 years after gastrectomy, regular follow-up should be done every year.
General examination routine for gastric and cardia cancer specimens
Appendix A
Descriptive records
(whole stomach, large part of stomach or remnant stomach) resection specimen: length of greater curvature cm, length of lesser curvature cm, attached pyloric ring/duodenum/lower esophagus, length cm; in (cardia/fundus/body/sinus; lesser curvature/greater curvature) see type (early and progressive) mass (including appearance description): cm from upper incisional margin, cm from lower incisional margin, size — ×– ×– cm, cut surface properties; depth of infiltration to ; Involvement/non-involvement of the pyloric ring/inferior esophagus.
What was seen on examination within the mucosa/muscular wall of the esophagus next to or around the mass (erosion/roughness/granularity/depression/plaque//negative if necessary). Lymph nodes were found in the greater curvature (several/many/decades/dozens), diameter to cm; lymph nodes were found in the lesser curvature (several/many/decades/dozens), diameter to cm. Large omentum, size — x — x — cm, presence of tumor and lymph nodes.
Appendix B
Contents of pathological diagnosis report of gastric cancer
1.Tumor
(1) Tissue typing
(2) Tissue grading
(3) Depth of infiltration
(4) Esophageal or duodenal infiltration (if excised)
(5) Vascular infiltration
(6) perineural infiltration
2.Cut margin
(1) Proximal
(2) distal
3.Other pathological findings
(1) chronic gastritis
(2) Intestinalization
(3) atypical hyperplasia
(4) atrophy
(5) Adenoma
(6) polyp
(7) H. pylori
(8) Others
4.Regional lymph nodes (including small bend, large bend, large omentum and separately sent lymph nodes)
(1) Total number
(2) Number of involved lymph nodes
5.Distant metastasis
6.Other tissues/organs
7, special auxiliary findings (histochemical staining, immunohistochemical staining, etc.)
Pathology with difficulties submitted to higher level hospital consultation (provide original pathology report to verify the correctness of the submitted sections to reduce errors, provide adequate lesion sections or wax blocks, and what was seen intraoperatively, etc.)
Appendix C
Patient status score
C.1 Karnofsky score (KPS, percentage method)
The scores are shown in Table A.1.
Table A.1 Karnofsky score
100
90
80
70
60
50
40
30
20
10
0
Normal, no signs and symptoms, no evidence of disease
Normal activity with mild signs and symptoms
Barely able to perform normal activities with some symptoms or signs
Can take care of himself/herself, but cannot maintain normal life or work
Can mostly take care of themselves, but occasionally need help and cannot perform normal tasks
Needs some help and care, and medication
unable to take care of themselves and need special care and treatment
Severely unable to take care of himself/herself and has indications for hospitalization, but not yet seriously ill
Severely ill, completely incapacitated, requiring hospitalization and active supportive care
Critically ill, close to death
Death
C.2 Zubrod-ECOG-WHO score (ZPS, 5-point scale)
See Table A.2 for scores.
Table A.2 Zubrod-ECOG-WHO
0
1
2
3
4
5
Normal activity
Mild symptoms, self-care, able to engage in light physical activities
Can tolerate the symptoms of tumor, self-care, but not more than 50% of the time in bed during the day
Severe tumor symptoms, more than 50% of the time in bed during the day, but still able to get up and stand, partially self-care
Severely ill and bedridden
and confirmed composition