China belongs to the countries with high incidence of gastric cancer, and about 35% of new gastric cancer cases occur annually worldwide. According to the data of 2011 Annual Report of China Tumor Registry, the incidence rate of gastric cancer ranked the 2nd of tumors in the national tumor registration area (incidence rate 37.88/100,000), among which the incidence rate of men ranked the 2nd (incidence rate 51.63/100,000) and the incidence rate of women ranked the 4th (incidence rate 23.91/100,000).
Gastric cancer mortality rate Gastric cancer incidence rate ranked 2nd (mortality rate 26.58/100,000) among tumors in the national tumor registration area, with male mortality rate ranking 3rd (mortality rate 35.76/100,000) and female mortality rate ranking 4th (mortality rate 17.25/100,000). Rural morbidity was 68% higher than urban, and rural mortality was 82% higher than urban, with the highest in the northwest. Males were higher than females, with a ratio of 1.5 to 2.5/1.
Etiology
The exact etiology of gastric cancer is not yet clear. The development may be related to dietary factors, chemical carcinogens (nitrosamines, polycyclic aromatic hydrocarbons and asbestos fibers), environmental factors, H. pylori infection and genetic factors.
Pathology
According to the infiltration depth and metastasis of gastric cancer, it is classified into early stage and progressive stage gastric cancer. Early stage gastric cancer refers to those whose tumor infiltration does not exceed the submucosa layer; progressive stage gastric cancer refers to middle or advanced gastric cancer whose tumor infiltration exceeds the submucosa layer or is accompanied by metastasis.
(I) Precancerous disease and precancerous lesion Precancerous disease refers to certain clinical conditions or diseases that cause an obvious increase in the risk of occurrence of gastric cancer.
It is a clinical concept. The main precancerous diseases are.
① chronic atrophic gastritis: cancer rate of 7% to 10%.
②Gastric ulcerative disease: the cancer rate of gastric ulcer is 1-5%.
③Gastric polyps: the cancer rate of multiple polyps is higher than that of single polyps; adenomatous polyps is higher than that of hyperplastic polyps; polyps with wide base and no tip are easy to become cancerous, and the cancer rate is about 11%.
The incidence of residual gastric cancer after Billroth II surgery is 2 to 12 times higher than that of Billroth I. The cancer rate is about 10%.
Pre-cancerous lesion: It refers to the pathological histological changes of gastric mucosa that are prone to cancer, and is a pathological concept. The process is continuous, including normal → hyperplasia → atypical hyperplasia → carcinoma in situ → infiltrating carcinoma.
(II) Occurrence sites of cancer The occurrence sites of gastric cancer according to anatomical division are cardia cancer, gastric body cancer and gastric sinus cancer. Sinus cancer is common in China, while cardia cancer is common in developed countries in Europe and America. In recent years, it is clinically found that the trend of high gastric body and cardia cancer is obviously increasing.
(C) Gross staging of cancer At present, Borrmann’s gross staging of gastric cancer is still commonly used at home and abroad.
Type 0: The tumor mainly spreads along the mucosa or submucosa, also called superficial spread type.
Type I: The tumor mainly grows into the gastric lumen and is polyp-like, with clear borders, no ulceration and inconspicuous infiltration.
Type II: The tumor forms obvious ulcers with elevated ulcer margins and ring dyke like changes, and the infiltration is not obvious.
Type III: The tumor showed obvious ulcer with slope like edge and obvious infiltrative changes.
Type IV: The tumor shows obvious infiltrative changes, mainly infiltrating into the submucosa, muscle layer and subplasma. It is often called “leathery stomach” or “leathery stomach” in clinical practice.
Our Gastric Cancer Collaborative Group classifies the general types of gastric cancer into 9 types: nodular mycosis fungoides, discoid mycosis fungoides, local ulcer, infiltrative ulcer, local infiltrative type, diffuse infiltrative type, surface diffusion type, mixed type and multiple carcinomas.
(IV) Histological classification The histological classification of gastric cancer mainly uses the WHO international staging standard and is divided into 9 types: papillary adenocarcinoma, tubular adenocarcinoma, mucinous adenocarcinoma, indolent cell carcinoma, adenosquamous carcinoma, squamous cell carcinoma, carcinoid carcinoma, undifferentiated carcinoma, and unclassified carcinoma.
(E) Special gastric cancer pathological concepts
1.Early gastric cancer The primary focus of gastric cancer is limited to the intra-mucosa and sub-mucosa layer. This definition does not involve the size of tumor, lymph node metastasis and tumor stage. Some early gastric cancers can be more than 7 cm in size; some early gastric cancers can have second station lymph node metastasis.
Early gastric cancer includes the following special types.
①Micro gastric cancer (MGC): It refers to those with tumor diameter less than 5 mm.
②Small gastric cancer (SGC): It refers to those with tumor diameter of 5.1-10 mm.
③Small gastric cancer: also belongs to the scope of micro gastric cancer, which refers to the tumor lesion is very small, smaller than 5mm cancer foci, only diagnosed as cancer in gastric mucosal biopsy, but the cancer tissue cannot be found in the surgical resection specimen by series of examination.
④ Early gastric cancer of the remnant stomach: It refers to early gastric cancer occurring in the remnant stomach.
⑤ Multiple early gastric cancers: It refers to the occurrence of more than 2 independent early cancer foci in the same stomach and at the same time (6 months). It is reported in the literature that its incidence accounts for 6% to lO% of early gastric cancer. The 5-year survival rate of multiple primary early gastric cancers is about 10% lower than that of single early gastric cancer.
2.Progressive gastric cancer Progressive gastric cancer refers to the tumor infiltrating the muscle layer of gastric wall and below. It accounts for the majority of gastric cancer and is the main clinical problem.
3.Advanced gastric cancer Advanced gastric cancer refers to those with extensive infiltration and metastasis of gastric cancer, which cannot be treated radically.
(6) Infiltration and metastasis of cancer
(1) Direct infiltration refers to the spreading of tumor cells along the tissue interstices to the surrounding areas. It can infiltrate upward to the lower part of esophagus and downward to the lower pylorus and upper duodenum; it can infiltrate outward to the plasma membrane and then invade the adjacent organs, such as liver, bile, pancreas, spleen, transverse colon, mesentery and peritoneum, etc. It is the main reason for the difficulty of tumor resection and inability of resection.
(2) Lymphatic metastasis Literature reports that the lymph node metastasis rate of early gastric cancer is 3.3%~33%, and that of progressive gastric cancer is 56%~77%. Generally, the lymphatic metastasis of gastric cancer moves from the first station near the stomach wall to the second and third stations.
Grouping of gastric lymph nodes The peripheral lymph nodes of stomach are divided into 20 groups.
They are as follows
① Right lymph node of cardia;
②Left lymph node of cardia;
③Lymph nodes of the lesser curvature of the stomach;
④Gastric greater curvature lymph nodes;
⑤ suprapyloric lymph nodes;
⑥Subpyloric lymph nodes;
(7) Left gastric arterial trunk lymph node;
⑧ common hepatic artery trunk lymph nodes;
⑨ peri-abdominal artery lymph nodes;
⑩ splenic hilar lymph node;
No display of splenic artery trunk lymph nodes;
⑫hepatoduodenal ligament lymph nodes;
⑬Pancreatic posterior lymph nodes;
⑭ Mesenteric root lymph nodes;
⑮ Lymph nodes around the middle colonic artery;
⑯peri-abdominal aortic lymph nodes;
⑰ Anterior pancreatic lymph nodes;
⑱ Subpancreatic lymph nodes;
⑲ Subdiaphragmatic lymph nodes;
⑳ esophageal lymph nodes.
(3) Hematologic metastasis The most common site of hematologic metastasis of gastric cancer is the liver, which mainly metastasizes through the portal vein, followed by the lung, and a few may metastasize to the pancreas, bone, brain and other sites.
(4) Special metastasis Peritoneal implantation metastasis refers to gastric cancer cells infiltrating the plasma membrane and shedding to the peritoneal cavity to form implantation metastasis. Implantation lesions can be distributed on any organ surface of the peritoneal cavity. The metastasis of peritoneum can be found in clinical physical examination with thickening, toughening and increased tension of abdominal wall; the implantation metastasis of pelvic floor can be found by anal finger examination with implantation nodules in pelvic floor.
Jumping metastasis is also another special metastasis mode; in addition, there are ovarian Krukenberg tumor, metastasis of the uterine cervix; there are supraclavicular lymph node metastasis along the thoracic duct and a few left axillary lymph node metastasis; umbilical metastasis along the round ligament lymphatic vessels.
(VII) Clinicopathological staging The staging of gastric cancer is a very important basis for the design of gastric cancer diagnosis and treatment plan. At present, the TNM staging method of gastric cancer by the International Union Against Cancer (UICC) in 1985 is commonly used at home and abroad. This staging was modified by WHO in 2010 (7th edition), and the modified staging is as follows: T represents the depth of primary tumor infiltration into the stomach wall.
T1a: tumor invades the intrinsic mucosal layer or mucosal muscle layer; T1b: tumor invades the submucosal layer; T2: tumor invades the intrinsic muscle layer; T3: tumor penetrates the connective tissue of the subplasma layer without invading the dirty peritoneum or adjacent structures;
T4a: tumor invaded the plasma membrane (visceral peritoneum); T4b: tumor invaded adjacent tissue structures. N0: no metastasis in regional lymph nodes; N1: 1-2 regional lymph nodes with metastasis; N2: 3-6 regional lymph nodes with metastasis; N3: 7 and more regional lymph nodes with metastasis; N3a: 7-15 regional lymph nodes with metastasis; N3b: 16 (inclusive) or more regional lymph nodes with metastasis.
M indicates the distant metastasis of the tumor. M0: no distant metastasis; M1: presence of distant metastasis. Those with metastasis in the 12th, 13th, 14th and 16th groups of lymph nodes are also considered as distant metastasis. Now, according to the different combinations of TNM, gastric cancer can be divided into I-IV clinicopathological stages
If the primary tumor is confined to the mucosal layer without invading the lamina propria, it is considered as carcinoma in situ, which is indicated by Tis, and TisN0M0 is considered as carcinoma in situ and is called stage 0. Due to the advancement of diagnostic technology, the clinical staging performed to make judgment on tumor infiltration and metastasis before surgery is expressed as CTNM, while the pathological staging after surgery is expressed as PTNM.
Clinical manifestations
(I) Symptoms The occurrence and development of gastric cancer is a slow and long-term process, therefore, the appearance of symptoms is also a process from insidious interruption to continuous aggravation.
The common symptoms of gastric cancer are as follows.
① Abdominal distension and pain is the most common symptom. Initially, the pain is insidious and intermittent, and gradually develops into continuous. About 80% of patients have painful manifestations.
②Loss of appetite and emaciation are common symptoms. The tumor causes the loss of appetite due to the loss of gastric motility, and even wasting, and the wasting is very obvious in individual patients.
③Eating obstruction and vomiting are mainly manifested by pancreatic cancer, while vomiting is caused by pylorus or gastric sinus tumor, and the vomiting is often large in volume with a large amount of persistent food.
④Vomiting blood, black stool, anemia About 30% of gastric cancer patients have the manifestation of upper gastrointestinal bleeding. Generally, the bleeding is small and most of them can stop on their own, but it is mostly manifested as repeated bleeding. Long-term bleeding can cause anemia. Large amount of bleeding is manifested as vomiting blood, and sometimes emergency surgery is needed to stop the bleeding. Black stool is a special manifestation of gastric bleeding, with a tarry appearance.
(B) Signs of gastric cancer Most early gastric cancers do not have obvious signs, and most of the signs are the manifestations of advanced gastric cancer.
Common signs include.
(i) pressure pain in the upper abdomen is often more diffuse and the localization is not clear; in a few patients, the pressure pain is obvious and accompanied by rebound pain and muscle tension.
②Lymph node enlargement is mainly metastatic lymph node enlargement. The common one is left supraclavicular lymph node metastasis, and a few have left axillary lymph node metastasis.
Ascites and pelvic floor implantation nodes As the tumor spreads in the abdominal cavity, it causes ascites and pelvic floor implantation nodes. Cancer cells can be detected by ascites examination; metastatic nodes in the pelvic floor can be detected by anal finger examination.
(4) Obstruction and jaundice The tumor in the gastric sinus or pylorus may cause pyloric obstruction due to the small size of the gastric cavity, and intestinal adhesions due to the intraperitoneal spread of gastric cancer, resulting in gastrointestinal obstruction; the enlarged lymph nodes in the hepatic hilum and extensive liver metastasis may cause jaundice.
⑤ Anemic appearance, wasting and cachexia are all manifestations of advanced tumors, which are very common in gastric cancer.
(C) Tumor-associated syndromes of gastric cancer Gastric cancer often has clinical manifestations of tumor-associated syndromes, the common ones are: acanthosis nigricans, palmar acanthosis, round furunculosis, bright red skin papilloma, dermatomyositis, polymyositis, hypoglycemia and hyperglycemia, etc.
Diagnosis
It is no longer difficult to diagnose gastric cancer through barium X-ray and fiberoptic gastroscopy plus biopsy. However, half of the early gastric cancers are asymptomatic, and patients do not go to the clinic until they have obvious symptoms, and coupled with the lack of effective and convenient screening means, early gastric cancers account for less than 10% of the total detection rate of gastric cancers in China at present. In order to improve the detection rate of early gastric cancer, people with family history of gastric cancer or history of chronic gastric disease should be screened regularly. Screening should be conducted for high-risk groups over 40 years old to prevent the detection of gastric cancer.
At present, the following four kinds of tests are mainly used to diagnose gastric cancer in clinical practice.
1.Barium X-ray examination is still a common method to diagnose gastric cancer. It can make the diagnosis by observing the mucosal phase and filling phase through the dual gas-barium imaging. The main change of early gastric cancer is often abnormal mucosal phase, and the morphology of progressive gastric cancer is basically the same as the general typing of gastric cancer.
2.Fiber gastroscopy can visualize the location and scope of gastric mucosal lesions, and can clamp lesion tissues for pathological examination, which is the most effective method to diagnose gastric cancer, and multi-point biopsy (more than 4 points) of suspicious lesions can help improve the diagnosis rate. Techniques such as stained gastroscopy and autofluorescence gastroscopy can significantly improve the detection rate of small gastric cancer and micro gastric cancer. Using fiber optic gastroscope with ultrasound probe, ultrasound detection and imaging of the lesion area can help to understand the depth of tumor infiltration and whether there is invasion and metastasis of surrounding organs and lymph nodes, and can also be used for ultrasound-guided deep sampling.
3.Abdominal ultrasound is mainly used to determine the infiltration and lymph node metastasis of the adjacent organs of stomach (especially liver and pancreas).
4.Spiral CT and positron emission tomography (PET/CT) examination Multi-row spiral CT scan combined with three-dimensional reconstruction and simulated endoscopic technology is a new non-invasive examination tool, which is helpful for the diagnosis and preoperative clinical staging of gastric cancer. Using the affinity of gastric cancer tissue for [18F]fluoro-2-deoxy-D-glucose (FDG), PET/CT can determine lymph nodes and distant metastatic lesions with relatively high accuracy.
Treatment
The principle of comprehensive treatment should be adopted clinically, that is, according to the patient’s organism condition, pathological type, invasion range (disease stage) and development tendency of tumor, the existing treatments should be applied in a planned and reasonable manner, with the aim of maximizing the eradication and control of tumor and increasing the cure rate, and improving the patient’s quality of life.
(I) Surgery is divided into two types: radical surgery and non-radical surgery.
Radical surgery requires the removal of part or all of the stomach, including the cancer foci and the possible infiltration of the stomach wall, and the removal of the lymph nodes around the stomach and the reconstruction of the digestive tract according to the clinical stage.
(1) Scope of gastric resection: In surgery for the purpose of radical treatment, the scope of resection should be decided in such a way that the distance from the cut edge to the tumor margin is sufficient. It is important to ensure the following margin distances (invasive esophageal cancer does not follow this limit): 75px for limited tumors above T2 and 125px for infiltrative type. If the margin distance is lower than the above requirements, a rapid pathological examination of the entire proximal margin of the tumor should be performed for clarification.
(2) Lymph node clearance range: The lymph node clearance range is indicated by D(dissection), and the perigastric lymph node station is indicated by N. The radical degree of gastric cancer surgery is divided into A, B and C. Grade A: D>N, the lymph nodes removed by surgery exceed the lymph nodes with metastasis; there is no cancer cell infiltration within 1 cm of the cut edge. Grade B: D=N, or there is cancer infiltration within 1 cm of the cut edge. No tumor residue, but estimated to be slightly inferior to grade A radical treatment. grade C: only primary cancer foci and part of metastatic cancer foci are removed, and there is still tumor residue, which is non-radical surgery.
(3) Surgery mode: determined according to tumor site, progression degree and clinical stage. For early stage gastric cancer, laparoscopic or open partial gastrectomy can achieve the purpose of radical treatment because of less lymph node metastasis. Endoscopic mucosal resection (EMR) is feasible for well differentiated indurated mucosal carcinoma (within 1 cm) without ulceration or scar formation, and elevated mucosal carcinoma less than 2 cm in diameter.
For progressive gastric cancer, the surgical goal is to achieve R0 resection, and gastrectomy with D2 lymph node dissection is considered as the standard treatment. For distal gastric cancer, radical distal gastrectomy is required to remove 3/4 to 4/5 of the stomach, remove lymph nodes at one or two stations, remove the greater and lesser omentum, the anterior lobe of the transverse colonic mesentery and the pancreatic peritoneum; gastrointestinal reconstruction is optional with gastrojejunostomy Billorthn type I or II anastomosis, or residual gastrojejunostomy Roux-en-Y anastomosis.
Gastric body cancer usually undergoes radical total gastrectomy, and GI reconstruction is often performed by esophageal-jejunal Roux-en-Y anastomosis, or duodenoesophageal-jejunal interposition surgery. For proximal gastric cancer, radical proximal gastrectomy, residual gastroesophageal anastomosis or jejunal interposition may be used.
Expanded combined resection: it is applicable to gastric cancer directly infiltrating surrounding tissues or organs, such as radical major gastrectomy or total gastrectomy for combined pancreatic body, tail and spleen part of liver or colon.
2.Palliative gastrectomy surgery The primary foci can no longer be removed, and the surgery is performed to relieve the symptoms caused by complications such as obstruction, perforation and severe bleeding, including gastrojejunostomy, jejunostomy, perforation repair, etc.
(II) Chemotherapy for gastric cancer It is used for preoperative, intraoperative and postoperative of radical surgery to prolong the survival. Appropriate chemotherapy for patients with advanced gastric cancer can slow down the development of tumor, improve symptoms and have certain recent effects.
In principle, adjuvant chemotherapy is not necessary after radical surgery for early gastric cancer, but adjuvant chemotherapy is needed for those with high-risk factors: high malignancy of pathological type; pulsed or lymphatic invasion; cancer foci area greater than 125px2; multiple cancer foci. Those with progressive gastric cancer after radical surgery, palliative surgery, or postoperative recurrence need chemotherapy. Patients who need to receive chemotherapy must have clear pathological diagnosis, good general condition, no significant abnormalities in heart, liver, kidney and hematopoietic function, and no serious combined diseases.
2.Drug delivery methods Commonly used drug routes include oral, intravenous and peritoneal drug delivery. In order to improve the therapeutic effect, multiple chemotherapeutic drugs are often used in combination. Commonly used chemotherapeutic drugs for gastric cancer: 5-fluorouracil, cisplatin, etoposide, adriamycin, mitomycin, oxaliplatin, paclitaxel, capecitabine, tegeo (S1), etc.
There is no definite standard treatment chemotherapy regimen for gastric cancer, commonly used chemotherapy regimens: CF regimen (cisplatin/5FU); ECF regimen (epothilone/cisplatin/5-FU) and its modified regimen (oxaliplatin instead of cisplatin and/or capecitabine instead of 5FU); ELF regimen (etoposide/calcium folinic acid/5-FU);
FAM regimen (5FU/adriamycin/mithramycin).
(C) Other treatments for gastric cancer include radiotherapy, targeted drug therapy, thermotherapy, immunotherapy, Chinese herbal medicine, etc. With the recognition and application of multidisciplinary integrated treatment model, various treatments for gastric cancer will tend to be rationalized.
Prognosis
The 5-year survival rate of gastric cancer after radical surgery depends on the depth of invasion of the gastric wall, the extent of lymph node involvement and the tumor growth pattern. According to the literature, the 5-year survival rate of stage I gastric cancer with standard treatment is 85%-95%, stage II is 55%, stage III is 15%-30%, and stage IV is only 2%. The prognosis of esophagogastric cancer is relatively poor because most of the patients are in advanced stage when they are diagnosed and more than 80% of them have lymph node metastasis at the time of surgery. At present, the detection rate of early gastric cancer in China is low, which has a great impact on the prognosis, and increasing the early diagnosis rate can help improve the 5-year survival rate of gastric cancer.