Over the past several years, more and more individuals attract malignant gastric cancer. In many cases, however, the initial symptoms of the disease are so non-specific that the tumor is not diagnosed until it is in an advanced stage resulting in the prognosis being worse. Which risk factors promote the development of gastric cancer and what are the treatment options once the diagnosis of gastric carcinoma has been made? In the following article you will find out everything you need to know about gastric cancer.

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Adenocarcinoma low differentiated

Image: “Histological preparation of a slightly differentiated gastric Adenokarzinomes .” by Kwz. License: Public Domain

Definition of Gastric Cancer

Malignant epithelial neoplasms with gastric cancer (ICD code C16.9)

Gastric cancer refers to the formation of malignant epithelial neoplasms of the stomach and is the second most common tumor of the gastrointestinal tract.

Epidemiology of Gastric Cancer

The continuing decline of incidences of gastric cancer in Western Europe

This is a tumor that occurs particularly often in countries such as China and Japan. In Western Europe, the trend is declining. Men are slightly more affected than women, with the disease’s peak of incidence being over the age of 50. Gastric cancer usually has an unfavorable prognosis as its initial symptoms are rather non-specific resulting in the disease not being diagnosed until it reaches a more advanced stage and because it metastasizes early on.

Stomach cancer in advanced stage

Image: “Stomach cancer in advanced stage” by Robert Weemeyer. License: Public Domain

Etiology of Gastric Cancer

Factors that promote the development of gastric cancer

There are indicators for a connection between one’s nutritional habits and the occurrence of gastric cancer. Especially foods rich in nitrate are suspected to promote the development of cancer, whereas foods rich in fiber and antioxidants are thought to protect the stomach.

The biggest risk factor, however, was and is gastritis caused by Helicobacter pylori, followed by type A gastritis. A Helicobacter pylori infection increases the risk for carcinoma between four and six times.

Furthermore, partial gastrectomy, the presence of certain gastric adenomatous polyps, and giant fold gastritis pose a certain risk for gastric cancer. Stomach ulcers, however, rarely degenerate.

The following diseases pose a risk for gastric cancer:

Symptoms of Gastric Cancer

Gastric cancer may remain undetected for a long time as the initial symptoms are too non-specific. There may be symptoms such as upper abdominal pressure and nausea, night sweats, less energy and weight loss. A sudden aversion to meat may be an indicator for gastric cancer as well.

If the tumor growth has reached an advanced stage, the Virchow’s lymph node (left supraclavicular lymph node) is palpable, hepatomegaly and ascites occur. In cases of aggressive, metastasizing growth, malignant acanthosis nigricans (acanthosis nigricans maligna) or cutaneous paraneoplastic syndrome may occur. In many cases, however, the complications of the tumor such as pyloric stenosis and bleeding are the first significant symptoms of the disease.

Diagnosis and Clinical Signs of Gastric Cancer

The histological examination of gastric cancer

The following options are available for diagnosing gastric cancer:

  • Gastroscopy with multiple biopsies
  • X-rays with contrast agents
  • TNM staging using:
    • Endosonography
    • Chest x-rays
    • Abdominal CT
    • Abdominal sonography
    • Skeletal scintigraphy

The tumor markers CA 19-9, CA 72-4 and CEA are relevant for monitoring the progression of the tumor.

Most histological examinations will detect adenocarcinoma but also the so-called signet ring cell carcinoma. Signet ring cell carcinoma is an adenocarcinoma, whose cells produce large amounts of mucus pushing the nucleus against the cell membrane, morphologically resulting in the typical signet ring appearance. Signet ring cell carcinomas have a rather negative prognosis. Squamous cell carcinoma, gelatiniform cancer, small cell carcinoma and undifferentiated carcinoma are rarer forms of cancer.

Location and spread of gastric cancer

Gastric cancer is most commonly located in the antrum and pylorus followed by the lesser curvature and cardia.

Note: This tumor metastasizes early!
Bone metastases in gastric carcinoma

Image: “Bone metastases in gastric carcinoma” by Hellerhoff. License: CC BY-SA 3.0

How gastric cancer spreads:

  • Metastases in ovaries (Krukenberg tumor) or in the pouch of Douglas
  • Hematogenous spread to liver, lungs, bones and brain
  • Invasion, per continuitatem, into the esophagus, duodenum, colon and pancreas
  • Infiltrates the gastric wall and the peritoneum
  • Lymphogenous metastasis to lymph nodes along the lesser and greater curvature, the celiac artery (truncus coeliacus), the para-aortic and mesenteric lymph nodes
Note: 30 % of affected individuals with stage pT1b cancer have lymph node metastases!

Classification of Gastric Cancer

The classification systems for gastric carcinoma

The so-called Lauren’s classification groups gastric cancers according to their histological growth pattern:

  • The intestinal typehas a more favorable prognosis as the tumor grows expansively but has a distinct border.
  • The diffuse type infiltrates, possibly penetrating surrounding organs and has a rather negative prognosis due to its tendency to quickly metastasize to the lymph nodes.
  • Furthermore, there are mixed type of gastric cancer.

Histologically, the degree of differentiation (grading) of the tumor is determined, G1 being well-differentiated and G4 being undifferentiated.

Macroscopic classification according to Borrmann:

  • ulcerative
  • polypoid
  • ulcerative-polypoid
  • infiltrating growth

    ulcerating gastric carcinoma

    Image: “ulcerating gastric carcinoma” by Kuebi. License: CC BY-SA 2.0

Classification based on location:

  • Approximately 70 % of tumors are located in the antrum.
Note: The frequency of distal gastric cancer has declined, which is attributed to implementing eradication therapy for Helicobacter pylori infections.
  • lesser curvature
  • cardia
  • tumors of the gastroesophageal junction
Note: Cancer of the gastroesophageal junction has become more and more frequent! For the past several years, the incidence of gastroesophageal cancer has sharply risen! Even after stage T0 resection and broad application of lymph node dissection, the recurrence rate is high with this specific tumor location.

The Siewert classification for adenocarcinoma of the gastroesophageal junction (AEG) is as follows:

  • AEG I : true carcinoma of the distal esophagus (Barrett’s esophagus, associated with reflux)
  • AEG II : true carcinoma of the cardia
  • AEG III : subcardial gastric carcinoma

As with any oncological disease, a staging, in most cases using the TNM classification system, takes place in order to assess the extent of the disease as well as to plan the therapeutic intervention.

The TNM classification groups tumors as follows:

T = Primary tumor according to depth of infiltration

  • Tis – carcinoma in situ
  • T1 – the tumor invades the submucosa
  • T2 – the tumor invades the muscularis propria
  • T3 – the tumor invades the serosa
  • T4 – the tumor perforates the serosa, surrounding structures are affected

N = regional lymph node involvement according to the number of lymph nodes affected

  • N0 – no regional lymph node metastases
  • N1 – 1 – 2 regional lymph node metastases
  • N2 – 3 – 6 regional lymph node metastases
  • N3 – 7 – 16 regional lymph node metastases

M = formation of distant metastases

  • M0 – no distant metastases
  • M1 – confirmed distant metastases

Following surgery, the residual tumor is assessed according to the R classification:

  • R0 = no residual tumor
  • R1 = microscopic residual tumor
  • R2 = macroscopic residual tumor

Therapy and Prognosis of Gastric Cancer

Standard therapy for gastric cancer is surgical R0 resection of the tumor. Smaller early cancers that are limited to the mucosa are suitable for endoscopic removal as well. Starting with stage T3, multimodal therapy consisting of perioperative chemotherapy and surgical intervention is recommended. In most cases, R0 resection means performing a gastrectomy, the total removal of the stomach to include the greater and lesser omentum and the lymph nodes.

With regard to tumors of the gastroesophageal junction, a distal esophagus resection is additionally performed. In later stages, once the tumor has already metastasized, the attempt is made to extend survival through palliative chemotherapy.

The prognosis of gastric cancer largely depends on the stage the tumor is in at the time of diagnosis. Carcinoma in situ has a five-year survival rate of 100 % and with regard to pT1N1M0 and pT2N0M0, it is still at 70 %. In all advanced stages, the deciding factor is how resectable the tumor is. If R0 resections have a five-year survival rate of up to 45 %, this rate decreases to almost zero with R2 and R3 resections!

Note: Following a gastrectomy, patients receive nutritional counseling. Furthermore, they will have to substitute vitamin B12 and pancreatic enzymes for the rest of their lives.

Other Gastric Tumors

Benign gastric tumors

Benign gastric neoplasms are rarer than malignant neoplasms and do not have to ability to infiltrate or metastasize. They are frequently found by accident. If they grow expansively, dysphagia and symptoms of pyloric stenosis may occur, depending on the location of the tumor. Therapy options consist of endoscopic removal (of polyps, cysts, hamartoma) or surgical removal of the tumor (in cases of larger mesenchymal tumors), which always carries the risk of bleeding and perforations with it.

Gastrointestinal stromal tumors (GIST)

Gastrointestinal stromal tumors are mesenchymal sarcomas that frequently occur in the stomach and small intestine. It is unusual to find GIST located outside the stomach, i.e. in the omentum or peritoneum, in which case they have a far more negative prognosis.

The incidence of GIST is 1/100.000 annually. The GIST diagnosis is confirmed via imaging procedures such as CT, MRT, and PET scans as well as a biopsy to provide histological findings. 90 % of these tumors express the antigen CD117, which is part of the c-KIT receptor. Therapy and prognosis of GIST significantly depend on the size of the tumor and its mitotic index.


Image: “CT GIST” by Inversitus. License: CC BY-SA 3.0

Small R0 resectable tumors that may have been treated with neoadjuvant therapy have a good chance of healing. Inoperable GISTs are preferably treated with the tyrosinkinase inhibitor imatinib. These tumors develop hepatic and peritoneal metastases. Most gastrointestinal stromal tumors are found by accident as there are only non-specific abdominal symptoms with GIST, in some cases there may be bleeding.

Other tumors may affect the stomach as well, i.e. the MALT lymphoma, which is considered to be part of the non-Hodgkin lymphomas.

Review Questions

The answers are below the references.

1. Which statement is not true? Symptoms of gastric cancer may be:

  1. In the advanced stage of gastric cancer, the Virchow’s lymph node can be palpable.
  2. Malignant acanthosis nigricans (acanthosis nigricans maligna), a cutaneous paraneoplastic syndrome, frequently occurs in the early stages of the disease.
  3. Pyloric stenosis and bleeding are complications due to tumor growth.
  4. A sudden aversion to meat may be an indicator of gastric cancer.
  5. Gastric cancer causes only non-specific symptoms in the beginning stages.

2. Which statement is not true? Causes of gastric cancer may be:

  1. The biggest risk for gastric cancer is gastroduodenal ulcer disease.
  2. An infection with Helicobacter pylori is a frequent cause of gastric cancer.
  3. Partial gastrectomy poses a certain risk of degeneration.
  4. Adenomatous gastric polyps may degenerate.
  5. Giant fold gastritis may be a cause of gastric cancer.

3. Which statement regarding metastasizing gastric cancer is not true?

  1. 70 % of patients have already developed lymph node metastases at the time of diagnosis.
  2. Gastric cancer metastasizes early on to the lymph nodes of the lesser and greater curvature.
  3. The Krukenberg tumor is a metastasis of gastric cancer in the ovaries or the pouch of Douglas.
  4. Per continuitatem, the tumor metastasizes into the esophagus, duodenum, colon, and pancreas.
  5. The hematogenous spread to the liver, lungs, bones and brain takes place during the early stages of the disease.
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