Second Opinion on Stomach cancer

Everything we eat and drink passes through the stomach. It takes in the food, processes it into a food pulp, and passes it on to the intestines in small portions.

The organ is actually a muscular tube located in the left upper abdomen. The inside of its wall is covered with a mucous membrane (gastric mucosa). In this lining there are glands producing gastric acid for digestion.

What is stomach cancer?

In general, malignant cells are those which multiply uncontrolled, displace healthy body tissue, and spread throughout the body. If the cancer originates from the stomach glandular tissue, the medical term for such a condition is gastric adenocarcinoma, or gastric cancer. It is the most common type of stomach malignancy. There are also far less frequent types, such as small cell carcinomas, lymphomas, neuroendocrine tumors and gastrointestinal stromal tumors.

If the disease progresses, metastases often settle in the liver, lymph nodes, lungs, and peritoneum (the serous membrane that lines the abdominal cavity).

What are the warning signs?

Complaints that can indicate stomach cancer are often ambiguous. At the beginning, one may feel some digestive discomfort, such as bloating, belching, poor appetite, bad breath or abdominal pain.

As the condition develops, these symptoms usually become more severe, and new ones appear. Signs that clearly signal danger are:

- difficulty swallowing;

- frequent vomiting;

- consistent loss of appetite;

- unwanted weight loss;

- bloody or black stool (tarry stool);

- iron deficiency (anemia).

One, let alone a few, of the above-mentioned complaints is a solid reason to see a doctor.

Stomach cancer diagnosis

The only reliable way to prove the presence of malignant growth in the stomach is to examine its tissue samples. The latter are obtained by biopsy performed with the help of upper endoscopy (gastroscopy), when a flexible tube is inserted into the stomach via the esophagus to view it from the inside and take specimens of suspicious-looking tissue. They are then referred to a pathology lab for analyses. It includes the basic malignant-or-benign differentiation and determination of the abnormal cell nature (glandular, lymphatic, etc.), as well as further tests aimed at revealing some particular features of cancer cells (the expression of HER2/neu protein).

Besides the tumor cell character, there are other factors that influence stomach cancer treatment strategy. The key ones are:

- the location of the primary mass;

- tumor size;

- the extent of its invasion into the neighboring tissue, lymph nodes and the presence of metastases in other organs.

To obtain all this date, doctors perform specific exams, including:

endoscopic ultrasound of the stomach;

liver sonography;

computed tomography.

 Sometimes a small surgery (laparoscopy) is also needed to check if the malignancy has spread into the peritoneum, because it may be overlooked by imaging studies.

What do the study findings mean?

All these exams are aimed at getting a clear picture of the disease, which first and foremost means knowing its subtype and stage. This knowledge is a key condition for working out an effective treatment plan.

Tumor subtypes

According to the Laurén classification, gastric adenocarcinomas are divided into the intestinal, diffuse and indeterminate (having an uncommon histology) type.

The World Health Organization (WHO) classification is more detailed and, in addition to the adenocarcinoma, describes other gastric tumors of lower frequency, taking into consideration histological characteristics as well as and molecular phenotype.

Both classifications have clinical and prognostic relevance; that is, they are important to understand how the disease will develop and how it should be managed.

Gastric cancer staging

Malignant tumors of the stomach are classified into stages based on the international TNM system that determines how far the disease has spread, taking into consideration three criteria:

T: size and extent of the primary tumor.  

N: number and location of affected lymph nodes.

M: absence or presence of secondary malignancies (distant metastases) in other organs.

The initial tumor classification is based on the imaging examinations. However, its exact staging is only possible after the operation, when the removed tissue has been examined in detail. Therefore, the final classification after surgery may be different from the initial one.

The stages range from 0 to IV:

Stage 0: the tumor is confined to the uppermost layer of the gastric mucosa and has not grown into deeper layers ("carcinoma in situ").

Stages I to III: the tumor has grown further into the gastric mucosa, the underlying connective tissue and muscle layers, or beyond the gastric wall into the adjacent tissues. Whether a stage I, II, or III is present depends on the extent of infiltration and on whether the lymph nodes are affected.

Stage IV: distant metastases are present; the tumor size or the number of affected lymph nodes is irrelevant.

Overview of gastric cancer treatment options

There are several therapy options applicable with stomach cancer.

I. Surgery

The main task is complete removal of the malignant lesion. The extent of surgical procedure depends on its size, growth type and location. If the stomach tumor is detected very early, when it is still less than 2 centimeters in size and has not grown beyond the innermost layer of the stomach wall (mucosa), it can be removed during a gastroscopy, which is called endoscopic resection. In this case, only the tumor and the directly adjacent tissue are taken out.

Should preliminary exams prove that the cancer has already grown through all wall layers of the stomach, or that it has spread to surrounding lymph nodes, an attempt should first be made to shrink it by chemotherapy. The standard duration of the preoperative (the so-called neoadjuvant) chemotherapy is about 8 weeks. In many cases, it then becomes possible to remove the malignant mass completely. Usually, therapy with cell-killing drugs is continued for another 8 weeks after the operation.

In course of stomach cancer surgery, either a part (subtotal gastrectomy) or all of the stomach (total gastrectomy) may be resected, including surrounding lymph nodes and possibly areas of the nearby tissue and adjacent organs (e.g., the lower part of the esophagus, the spleen, part of the pancreas). In the case of extensive surgery, the rest of the stomach or the end of the esophagus is connected to the small intestine to restore the passage of food. Whenever possible, various reconstructive techniques are used, including those creating an enteral pouch or a stomach reservoir which would simulate a reservoir of a normal intact stomach.

When metastases have already developed in the liver, peritoneum or more distant regions of the body, the disease can no longer be cured, and surgery is only performed in emergency situations, e.g., severe bleeding. In such cases, drug therapy options will be attempted. Still, surgery may be considered again if the tumor itself, or its metastases shrink under medications. According to the latest studies, it seems reasonable if the metastases were limited to lymph nodes in the abdomen before chemotherapy, and if surgery at this point could completely remove the gastric tumor and all its metastases.

II. Chemotherapy

Gastric carcinomas are now generally considered to have good sensitivity to drugs that stop cell growth (chemotherapy), although cytostatics alone are not enough to cure this type of cancer. However, it has been proven that, starting from certain tumor volume, their use before (and after) surgery improves the patients' chances of recovery.

Moreover, in the case of a locally advanced tumor, i.e., the one that cannot be completely taken out initially, pre-treatment with cytostatic drugs can achieve a tumor size reduction in about half of patients. This may subsequently make it possible to allow a complete surgical removal of the malignant mass.

In the case of advanced cancer that has already metastasized, the aim of chemotherapy is to reduce the size of the lesion, or at least to halt its growth for a certain time, and alleviate symptoms. However, the treatment does not work in all patients, so it must be monitored very carefully and should better be administered by physicians with solid experience in treating gastric cancer.

III. Antibody therapy

HER2 receptors are molecules that bind to certain substances, stimulating the cell growth. They are found in about 20% of all gastric cancers, which are called HER2-positive.

Treatment with an antibody aimed at fighting HER2 is now the standard therapy for metastatic stomach malignancies. The drug is administered as an infusion every three weeks in combination with palliative chemotherapy. Compared with chemotherapy alone, this can slow the disease and increase patients’ lifespan.

Another antibody called ramucirumab targets VEGF (vascular endothelial growth factor) receptors which influence the division of cells involved in supplying blood to malignant masses. It can be used alone or in combination with the cytostatic drug paclitaxel when platinum-containing chemotherapy is no longer effective.

There is also growing evidence that immunotherapy may be effective in gastric cancer as well. This refers to antibodies (known as immune checkpoint inhibitors) that are capable of lifting the blockade that the malignant cells impose on the body’s immune cells and enabling the body's immune cells to attack and destroy tumor cells again. These antibodies can be used alone or together with chemotherapy.

IV. Radiation

Radiation therapy is occasionally used for stomach cancer when a patient cannot be operated on, or does not respond to chemotherapy. It has proven effective in relieving pain and preventing bone fracture, especially with bone metastases.

After complete tumor removal, a combination of chemo- and radiotherapy is intended to prevent a relapse. However, so far such an effect has been confirmed only in cases when surgery did not include removal of the surrounding lymph nodes. Also, radiation may damage some important organs (the intestine, liver, lung, kidney) located right near the stomach.