I. Overview of Stomach Cancer
Gastric cancer is one of the common malignant tumors in China, and its incidence rate ranks first among all kinds of tumors in China. The incidence rate of gastric cancer in China is the highest in Northwest China, followed by Northeast China and Inner Mongolia, followed by East China and the coast, and the lowest in South Central and Southwest China, and about 170,000 people die of gastric cancer every year, which is almost 1/4 of all malignant tumor deaths, and more than 20,000 new gastric cancer patients are produced every year.
The causes of gastric cancer are unknown and may be related to a variety of factors, such as lifestyle habits, diet, environmental factors, genetic quality, mental factors, etc. It is also related to chronic gastritis, gastric polyps, gastric mucosal anomalous hyperplasia and intestinal epithelial hyperplasia, post-surgical residual stomach, and long-term Helicobacter pylori (HP) infection, etc. . Gastric cancer can occur in any part of the stomach, but it is mostly found in the gastric sinus, especially on the side of the gastric malleolus. According to the depth of cancer tissue infiltration, it is divided into early gastric cancer and progressive gastric cancer (middle and late gastric cancer).
Early symptoms of gastric cancer are often not obvious, such as elusive upper abdominal discomfort, vague pain, belching, acidity, loss of appetite, mild anemia and other symptoms similar to gastroduodenal ulcer or chronic gastritis. In some patients, the pain is reduced or relieved after taking painkillers, anti-ulcer drugs or dietary modifications, and is therefore often ignored without further examination. As the disease progresses, the symptoms of stomach gradually become obvious, such as epigastric pain, loss of appetite, emaciation, weight loss and anemia.
At the later stage, there are often metastasis, abdominal mass, enlarged left supraclavicular lymph node, black stool, ascites and severe malnutrition. Since gastric cancer is very common and dangerous in China, and the relevant researches believe that its causes are related to dietary habits and stomach diseases, it is very important to understand the basic knowledge about gastric cancer for its prevention and treatment.
Etiology
At present, the following factors are considered to be related to the occurrence of gastric cancer.
(i) Environmental factors
The significant difference in incidence rates between different countries and regions indicates that they are related to environmental factors, the most important of which is dietary factors. Excessive intake of salt, salted foods with high salt content, smoked fish, and nitrosamines are factors associated with the development of gastric cancer, as well as moldy foods containing more fungal toxins, and processed rice covered with talcum powder. In addition, there are also studies showing that stomach cancer is related to the loss of nutrient balance.
(B) Genetic factors: The incidence of stomach cancer is higher in some families. The incidence of stomach cancer in relatives of patients with stomach cancer is four times higher than that of normal people. Some data show that stomach cancer occurs more often in people with blood type A than those with blood type O.
(iii) Immune factors The incidence of gastric cancer is higher in people with low immune function.
(iv) Pre-cancerous changes Pre-cancerous changes refer to certain lesions with strong malignant tendency, which may develop into gastric cancer if left untreated. Pre-cancerous changes include precancerous conditions and precancerous lesions.
1.precancerous conditions of stomach
(1) Chronic atrophic gastritis: there is a significant positive correlation between chronic atrophic gastritis and the incidence of gastric cancer.
(2) Pernicious anemia: gastric cancer occurs in 10% of patients with pernicious anemia, and the incidence of gastric cancer is 5-10 times that of the normal population.
(3) Gastric polyps: Although adenomatous or villous polyps do not account for a high proportion of gastric polyps, the cancer rate is 15% to 40%. The cancer rate is higher for those with a diameter greater than 2 cm. Hyperplastic polyps are common, while the cancer rate is only 1%.
(4) Stomach remnant: the cancer that occurs in the stomach after surgery for benign gastric lesions is known as gastric remnant cancer. The incidence increases significantly after gastric surgery, especially from 10 years after surgery.
(5) Benign gastric ulcer: gastric ulcer itself is not a pre-cancerous state. Instead, the mucosa at the edge of the ulcer is prone to intestinal epithelial metaplasia and malignancy.
(6) Giant gastric mucosal fold disease (Menetrier’s disease): serum protein is lost through giant gastric mucosal fold and there is hypoproteinemia and swelling clinically, about 10% can become cancerous.
2.Pre-cancerous lesions of stomach
(1) Anaplastic hyperplasia and interstitial lesions: the former is also called atypical hyperplasia, which is a reversible pathological cell proliferation caused by chronic inflammation, and in a few cases, it is not carcinogenic. Interstitial gastric metaplasia (anaplasia) has more chances of carcinogenesis.
(2) Intestinal metaplasia: there are two types of small intestine type and large intestine type. Small intestine type (complete type) has the characteristics of small intestine mucosa and is better differentiated. The large intestine type (incomplete type) is similar to large intestine mucosa and can be divided into two subtypes: type IIa, which can secrete non-sulfated mucin; type IIb, which can secrete sulfated mucin, and this type is closely related to the occurrence of gastric cancer.
Staging and classification of gastric cancer
Staging of gastric cancer
(I) Site of gastric cancer can occur in any part of the stomach, more than half of them occur in the sinus, the lesser curvature and the anterior and posterior walls of the stomach, followed by the cardia, and relatively less in the body of the stomach.
(II) Specific morphological classification
Early gastric cancer is limited to mucosa and submucosa regardless of the extent of the early lesions. It can be divided into three types: elevated type (polyp type), superficial type (gastritis type) and depressed type (ulcer type). Type II is subdivided into three subtypes, IIa (elevated superficial type), IIb (flat superficial type) and IIc (depressed superficial type). Each of the above types can have different combinations. For example, IIc+IIa, IIc+III, etc. Early gastric cancer with a diameter of 5-10mm is called small gastric cancer, and those with a diameter <5mm are called micro gastric cancer. Both early gastric cancer and progressive gastric cancer can show upper gastrointestinal bleeding, often as black stool. Few early gastric cancers can show minor upper gastrointestinal bleeding symptoms, i.e. black stool or continuous positive occult blood in stool.
2.Middle and late stage gastric cancer, also called progressive gastric cancer, the cancerous lesions invade the muscular layer or the whole layer, and often have metastasis.
(1) Mycosis fungoides type (or polyp-like type): it accounts for about 1/4 of advanced gastric cancer, the cancer is limited, mainly growing into the lumen, nodular or polyp-like, with rough surface like cauliflower and central erosion and ulceration, also called nodular mycosis fungoides type. If the cancer is discoid, with elevated edges and central ulcers, it is called discoid mycosis fungoides.
There is a swelling protruding from the posterior wall of the small curvature of the gastric sinus, slightly lobulated, with an uneven and granular surface and vesicles. The base of the swelling is slightly narrow and subtibial, and the surrounding mucosa is not significantly infiltrated
(2) Ulcerated type: It accounts for about 1/4 of advanced gastric cancer, and is divided into limited ulcerated type and infiltrated ulcerated type, the former is characterized by limited, disc-shaped cancer with central necrosis. The former is characterized by a limited, disc-shaped cancer with central necrosis, often with a large and deep ulcer; the bottom of the ulcer is generally uneven, the edge of the ulcer is elevated in the shape of a dike or crater, and the cancer is infiltrated to a deeper layer, often accompanied by bleeding and perforation. The infiltrative ulcer type is characterized by infiltrative growth of the cancer, often forming a mass with obvious infiltration to the periphery and deeper, with central necrosis forming an ulcer, often invading the plasma membrane or lymph node metastasis earlier.
(3) Infiltrative type: This type is also divided into two types, one is limited infiltrative type, in which the cancer tissue infiltrates all layers of gastric wall, mostly limited to the sinus part, and the infiltrated gastric wall thickens and hardens, and the wrinkled wall disappears, mostly without obvious ulcers and nodules. If the infiltration is limited to a part of the stomach, it is called “limited infiltrative type”. The other type is diffuse infiltration type, also called leathery stomach, in which the cancerous tissue expands under the mucosa and invades all layers, with a wide range, making the gastric cavity smaller and the gastric wall thicker and stiffer, but the mucosa can still exist, and there can be congestion and edema without ulceration.
(4) Mixed type: two or more lesions of the above mentioned types co-exist at the same time.
(5) Multiple carcinomas: The cancerous tissues are multifocal and unconnected to each other. For example, gastric cancer occurring on the basis of atrophic gastritis may belong to this type, and it is mostly found in the upper part of the stomach body.
(C) Tissue typing According to the tissue structure, it can be divided into 4 types.
Adenocarcinoma: including papillary adenocarcinoma, tubular adenocarcinoma and mucinous adenocarcinoma, which are classified into three types: highly differentiated, moderately differentiated and poorly differentiated according to their degree of differentiation;
②Undifferentiated carcinoma;
(3) Mucinous carcinoma (i.e. Indolent cell carcinoma);
④Special type of carcinoma: including adenosquamous carcinoma, squamous cell carcinoma, carcinoid tumor, etc.
According to the histogenesis, it can be divided into two types.
①Intestinal type: the cancer originates from the epithelium of intestinal glandular metaplasia, the cancer tissue is better differentiated, and the giant form is mostly myxoid;
Gastric type: the cancer originates from the intrinsic mucosa of the stomach, including undifferentiated cancer and mucinous cancer, the cancer tissue is poorly differentiated, and the giant form is mostly ulcerative and diffuse infiltrative type.
(IV) Metastasis pathway
1.Direct dissemination Infiltrating gastric cancer can develop along the mucosa or plasma membrane directly into the stomach wall, esophagus or duodenum. Once the cancer invades the plasma membrane, it is easy to infiltrate into the surrounding adjacent organs or tissues such as liver, pancreas, spleen, transverse colon, jejunum, diaphragm, greater omentum and abdominal wall. When cancer cells are shed, they can also be planted in the abdominal cavity, pelvic cavity, ovaries and rectal and bladder sockets.
Lymph node metastasis accounts for 70% of the metastasis of gastric cancer. The lower part of the stomach often metastasizes to the lymph nodes under the pylorus, under the stomach and next to the celiac artery, while the upper part of the stomach often metastasizes to the lymph nodes next to the pancreas, next to the cardia and the upper part of the stomach. Advanced cancer may metastasize to periaortic and supra-diaphragmatic lymph nodes. Since the abdominal lymph nodes are in direct communication with the thoracic duct, it may metastasize to the left supraclavicular lymph node.
3.Bloodstream metastasis Cancer cells can be found in peripheral blood of some patients, and can metastasize to liver through portal vein, and reach lung, bone, kidney, brain, meninges, spleen and skin.
Two staging methods of gastric cancer
The main staging systems of gastric cancer are the 6th edition of UICC/TNM staging and the 13th edition of Japanese staging of gastric cancer, called JGCA staging.
1.1 UICC/TNM staging method The UICC/TNM staging method has been revised less frequently, and the latest version is the 6th edition (2002) The UICC/TNM system is purely clinical staging, and the stage of the disease should be determined before treatment. However, for gastric cancer, surgical findings are essential for its staging, as the main prognostic factors can be determined only after surgery. the UICC/TNM system it uses the degree of infiltration of the gastric wall (T), the presence of metastatic perigastric lymph nodes near the primary lesion (N) and the presence of distant metastases (M), including lymph nodes outside the perigastric area, as criteria for staging. stage N is determined by a minimum of 15 The number of lymph nodes with positive metastases was determined (1-6 for N1, 7-15 for N2, and >15 for N3). the most recent version of TNM staging (2002, 6th edition) includes pT2 pT2a and pT2b subgroups, representing confinement to the muscularis and subplasma layers, respectively. This is equivalent to T2MP and T2SS of the JGCA staging method.
1.2 Japanese staging method In 1962, the Japanese Association for the Study of Gastric Cancer published the 1st edition of the specifications for the study of gastric cancer. Staging consists of the extent of plasma membrane layer infiltration (S stage), the site of involved lymph nodes dependent on the location of the primary site (N stage), and the extent and location of distant metastases (M, H, and P stages correspond to distant metastases, liver, and peritoneal disease, respectively). In its 12th edition, the overall specification changed the S stage to the T stage system, which corresponds to the T stage of the UICC system. the JGCA staging method serially numbers all regional lymph node stations and divides them into 3 strata according to the location of the primary tumor. Such detailed lymph node grading is performed to guide surgical decisions on the extent and location of lymph node dissection so that any potentially involved lymph nodes can be removed based on the location of the primary gastric cancer and the depth of infiltration.
There are many changes in the most recent version of the JGCA staging method, such as the rules for EMR, staging of remnant gastric cancer, and the fact that peritoneal cytology has been incorporated into the staging. From a surgical point of view, the most important change in the latest version is the revision of lymph node staging, where the lymph node group has been changed from the previous 4 levels (N1 to N4) to 3 levels (N1 to N3), based on a detailed study of the effect of clearance of different occupying lymph nodes in different locations of tumors in the stomach. Some perigastric lymph nodes in specific tumor locations are no longer classified as regional lymph nodes but as sites of distant metastasis (M), because the involvement of these lymph nodes is rare and, if it occurs, indicates a poor prognosis.1 An example is the involvement of group 2 lymph nodes (left area of the cardia) in gastric sinus cancer. Currently, D2 resection can be used as the standard surgical treatment for progressive gastric cancer. d3 resection is an investigational treatment and is not the standard of care.