Signet ring cell cancer of the stomach

Signet ring-shaped gastric cancer ranks second in terms of malignancy after adenocarcinoma. It grows rapidly and metastasizes. The number of diagnosed cases of this form of neoplasm is growing rapidly, while the number of registered oncopathologies of other types is falling. This is due to the fact that the altered tissues have a number of characteristics that make treatment difficult.

Causes

Any type of cancer occurs due to the fact that some mutations occur in the cell, it stops responding correctly to signals from the outside and begins to multiply uncontrollably. Changes occur in genes that control cell reproduction, repair damaged DNA, and regulate apoptosis (programmed cell death). In each specific case, it is impossible to name the exact reasons due to which the mutations that caused cancer occurred. Only risk factors are known that increase the likelihood of developing cancer.

Who is at high risk?

It is known that one of the main risk factors for stomach cancer is the bacterium H. pylori. It is present in the body of approximately half of people; as a rule, infection occurs at a young age. Most often, H. pylori does not cause any problems, but sometimes it provokes the development of chronic gastritis, peptic ulcers and malignant tumors.

In signet ring cell carcinoma, the role of H. pylori is controversial. Tumors often develop in people whose stomachs do not contain bacteria.

The role of other risk factors for gastric malignancies, such as smoking, a diet high in salty and smoked foods, and chronic gastritis, in relation to signet ring cell cancer has not been sufficiently studied.

In some cases, the disease develops due to hereditary mutations (passed from parents to children) in the CDH1 gene. Somatic (not inherited) mutations in the APC gene may play a role.

Causes of the disease

The reasons for the mutation of healthy cells into malignant ones have not been reliably established. Doctors have identified a number of factors that increase the risk of developing adenogenic carcinoma of the organ.

Among them:

• genetic predisposition. The likelihood of carcinoma growth increases in patients whose immediate family members have had cancer;
• living in a region with an unfavorable environmental situation;
• smoking;
• a diet based on smoked meats, semi-finished products, pickles, food additives,
• malabsorption of nutrients;
• alcohol abuse;
• AIDS, HIV;
• colonies of Helicobacter pylori in the organ (increases the likelihood of carcinoma by 10-12 times);

People who have been diagnosed with diseases related to precancerous conditions should be especially attentive to their health.

The degeneration of cells and the spread of neoplasm occurs gradually. The earlier the pathology is identified, the greater the chance of prolonging the patient’s life.

Symptoms

In the early stages, the tumor does not manifest itself, so it is difficult to diagnose. As the disease progresses, some symptoms appear:

• causeless weight loss;
• decreased appetite;
• discomfort in the abdomen, usually above the navel;
• stomach ache;
• heartburn;
• quick satiety, feeling of a “full belly”, even if a person has eaten only a little;
• nausea;
• vomiting, in some cases mixed with blood;
• abdominal enlargement;
• pallor, weakness, dizziness, rapid breathing and pulse - signs of anemia as a result of internal bleeding;
• blood in the stool.

Most often, these symptoms do not indicate cancer, but other pathologies, for example, gastritis, peptic ulcers, and viral infections. But you won't know for sure until you visit a doctor and get checked. You should be especially wary if these symptoms persist for a long time and intensify.

Stages

Oncologists determine the stage of stomach cancer in accordance with the international TNM system. The size of the tumor and its spread to surrounding tissues (T), the presence of lesions in regional lymph nodes (N), and distant metastases (M) are taken into account.

In general terms, the classification is as follows:

• Stage I is a tumor that is located in the mucous membrane and does not grow into the deeper layers of the organ wall. Tumor cells may spread to regional lymph nodes.
• Stage II is a tumor that has grown into the muscle layer of the stomach wall, with more widespread involvement of the lymph nodes.
• Stage III is a tumor that has grown through the entire wall of the stomach or has spread to many nearby lymph nodes.
• Stage IV - there are distant metastases.

Forecast

The prognosis for undifferentiated gastric cancer in most cases is unfavorable. About 18-20% of patients overcome the five-year survival threshold. Much depends on the stage of development of carcinoma at which treatment was started.

Thus, in the case of successful surgery at stage I of the disease, up to 90% of patients live for more than five years, at stage II - up to 55%. After a relapse, the survival rate decreases to three months from its onset.

Attention: tumor recurrence in undifferentiated cancer in the first three years after surgery is diagnosed in 90% of cases.

If the adenogenic form of cancer was detected at stage IV, the prognosis is extremely unfavorable. Most patients die within a year. Only a few live for five years.

Classification of the disease

One of the important characteristics of cancer tumors is the degree of malignancy. It depends on the degree of differentiation, that is, on how much the tumor cells have changed, how much they differ from normal ones. The lower the degree of differentiation and the higher the degree of malignancy, the more aggressive the cancer will behave and the worse the prognosis.

And here, with signet ring cell cancer of the stomach, not everything is so simple. In Russia, it is traditionally classified as an aggressive tumor with a poor prognosis. And Japanese experts note that treatment results are usually the same as in the case of other types of stomach cancer. On the one hand, the tumor is poorly differentiated, as it is very different from normal tissue. At the same time, cancer cells produce mucus, so we can say that their differentiation is partially preserved.

Signet ring cell cancer of the stomach is classified as a diffuse tumor, as it tends to spread to most of the organ. Malignant tumors associated with mutations in the CDH1 gene are called hereditary diffuse gastric cancer .

Features of signet ring cell tumors

The histological type “ring cell gastric cancer” received its name due to the fact that its cells look like rings under a microscope. In the center of the cell is a vesicle filled with mucus, surrounded by a strip of cytoplasm. The nucleus is shifted to the periphery.

The main feature of neoplasms is the increased production of mucus, which significantly complicates diagnosis. The lining of the organ remains unchanged, the pathological cells are dispersed in abundant secretions and are not identified during endoscopic and radiographic examinations until the tumor reaches a significant size.

The cricoid neoplasm develops in several ways:

• endophytic - grows inward, capturing all layers of the organ wall;
• infiltrative - pathogenic cells quickly separate from the main focus and spread throughout the body.

Mixed forms of pathology development are also known. Other features of signet ring cell neoplasm include:

• rapid metastasis in most cases occurs in the abdominal organs, and not in the lymph nodes;
• latent course up to the stage of total organ damage;
• metastasis to the ovaries in women (13% of cases);
• lack of a clearly designated central hub;
• men suffer from this form of the disease two times less often than women;
• more often than other neoplasms it is diagnosed in young and middle-aged people.

Doctors do not have a clear opinion regarding the degree of differentiation of signet ring cell carcinoma cells. Traditionally, neoplasms are classified as a poorly differentiated form, since their tissues differ significantly from healthy ones. But the ability to produce mucus indicates partial preservation of differentiation.

Neoplasms are hormone dependent. They are more often formed in men with elevated testosterone levels, and in women - with excess estrogen synthesis.

Diagnostic methods

Typically, a malignant tumor is detected using gastroscopy, an endoscopic examination of the stomach. During this procedure, the doctor examines the mucous membrane of the organ, finds pathologically changed areas and performs a biopsy - obtains a fragment of suspicious tissue to examine it in the laboratory. Gastroscopy can be combined with ultrasound diagnostics - this study is called endosonography. An ultrasound sensor is located at the end of the endoscope; it is used to study the stomach wall, surrounding tissues, and lymph nodes.

Anemia and gastric bleeding can be detected by a complete blood count and a stool occult blood test.

In order to detect foci of cancer outside the stomach and assess the stage of cancer, computed tomography, MRI, and PET scans are performed. Diagnostic laparoscopy helps detect lesions in the peritoneum.

Treatment of signet ring cell cancer of the stomach

Currently, there is debate about whether treatment tactics should be different if a signet ring cell tumor is diagnosed based on the results of a biopsy in the stomach. In Russia there are no separate recommendations; treatment is carried out in accordance with standard recommendations for gastric adenocarcinoma (in accordance with the “Practical Guidelines for the Drug Treatment of Gastric Cancer”, version 2021).

Treatment tactics are determined by a medical council (surgeon-oncologist, chemotherapist, therapist, endoscopist, anesthesiologist), depending on the stage of the tumor and the patient’s condition.

Surgery

In cases where the tumor is resectable, the main treatment is surgical removal. Typically, a subtotal resection (removal of the upper, most part of the organ) or gastrectomy (removal of the entire stomach) is performed. At the same time, nearby lymph nodes are removed.

Such interventions can be performed laparoscopically - without an incision, through punctures in the abdominal wall. In this case, there is less tissue injury, minimal blood loss, the patient recovers faster and returns to normal life.

Chemotherapy

If the tumor grows deeply into the wall of the stomach, spreads to the lymph nodes, or is highly malignant, adjuvant (postoperative) chemotherapy is indicated.

For more advanced cancer, perioperative chemotherapy is prescribed: three courses of chemotherapy before surgery and three more after surgery.

Different combinations of chemotherapy drugs are used:

• XELOX - capecitabine + oxaliplatin;
• CF - cisplatin + fluorouracil;
• ECF - epirubicin + cisplatin + fluorouracil;
• ECX - epirubicin + cisplatin + capecitabine;
• EOX - epirubicin + oxaliplatin + capecitabine.

For metastatic cancer, chemotherapy may be the mainstay of treatment. The course is carried out for 18 weeks with follow-up or until the tumor begins to progress again.

Radiation therapy

Radiation therapy is usually given in combination with chemotherapy, a treatment called chemoradiotherapy. It is indicated in the following cases:

• if during the operation it was not possible to remove the entire tumor;
• if the results of a biopsy of the removed tumor reveal a positive resection margin (there are cancer cells near the cut line, which means they could remain in the body);
• if it was not possible to remove the required number of lymph nodes.

Signet ring cell tumors of the stomach do not respond well to chemotherapy and chemoradiotherapy, making it very difficult to treat in advanced stages. At the European Clinic, molecular genetic analysis of tumor cells can be performed - this helps to select the most effective drugs for a particular patient.

Targeted therapy

Targeted drugs work on specific “target molecules” that help cancer cells multiply quickly and survive. If certain markers are detected in the cells of stomach cancer, a targeted drug from the group of HER2 inhibitors, trastuzumab, may be prescribed.

Treatment

The most effective way to combat adenogenic stomach cancer is a combination of several methods:

• surgical;
• chemotherapy;
• radial

The operation is carried out in two ways:

• subtotal resection - involves cutting off a part of an organ with a tumor, obligatory capture of surrounding tissues, as well as nearby lymph nodes to stop the spread of malignant cells;
• gastrectomy - complete removal of the stomach.

Attention: the difficulty of eliminating adenogenic neoplasms lies in their infiltrative rapid growth, which makes it difficult to determine the boundaries between healthy and malignant tissues.

More than 50% of patients with this form of cancer are considered inoperable. In these cases, operations are aimed at mitigating the main complications of the disease. The patient can undergo:

• removal of part of the carcinoma tissue;
• gastrostomy placement;
• installation of a bypass from the stomach to the intestines and other interventions.

Surgeries for adenogenic cancer are combined with other methods of influencing malignant cells.

Radiation and chemotherapy

Depending on the timing of application, chemotherapy treatments are divided into two categories:

• non-adjuvant - carried out before surgery to stop the growth of a malignant tumor, reducing its size to operable;
• adjuvant - prescribed 4-6 weeks after the intervention to reduce the likelihood of metastasis and relapse of the disease.

Radiation therapy is used in a similar way. Separately, these techniques are ineffective against adenogenic cancer, but significantly increase the effectiveness of surgical treatment.

If intervention is not possible, the patient is prescribed chemo-radiation therapy. It slightly increases life expectancy, but alleviates the general condition of the patient.

Doctors strive to place radioactive elements or chemotherapy drugs as close as possible to the malignant focus. For example, cytostatics are injected into the arteries through which malignant tissue receives nutrition. This method is called intra-arterial polychemotherapy.

Also, adenogenic neoplasm is affected by placing radioactive grains in the patient’s stomach. Such techniques make it possible to have the maximum destructive effect on altered cells, practically without affecting healthy ones.

Recovery and life after treatment

The recovery period after removal of the stomach proceeds as follows:

• After surgery, the patient is fitted with a nasogastric tube, a thin tube with one end in the stomach and the other coming out of the nose. It is subsequently removed.
• While the patient is unable to eat on his own, nutrition is provided intravenously.
• After about a week, the patient completely switches to independent nutrition.
• Discharge from the hospital occurs 1–2 weeks after the intervention.
• Subsequently, you need to adhere to the diet recommended by your doctor.

After treatment is completed, you need to periodically go to the doctor for examinations and undergo examinations, and adhere to a healthy lifestyle.

Relapse, metastases

If distant metastases are detected with gastric cancer, the prognosis worsens. Such cancer cannot be removed surgically, because there are usually many foci, they can be very small in size and located in different organs. In such cases, palliative and symptomatic treatment is indicated. Doctors try to slow down the progression of the disease as much as possible, prolong the patient’s life, and relieve him of painful symptoms.

After successful treatment, cancer can recur. Therefore, the doctor will prescribe regular examinations and examinations.

What varieties do experts distinguish?

Israeli doctors distinguish several types of adenocarcinoma (glandular cancer) of the stomach: mucinous, papillary, and tubular.

In turn, each of these varieties is divided into the following subtypes (the difference is based on how differentiated the tumor is):

• highly differentiated adenocarcinoma of the stomach, requiring mandatory treatment (Israeli clinics specialize in it);
• moderately differentiated gastric adenocarcinoma;
• low-grade gastric adenocarcinoma (this carcinoma is poorly identified up to stage g3 or stage 3 and necessarily requires treatment, the best of which is chemotherapy in Israel);
• poorly differentiated gastric adenocarcinoma;
• undifferentiated adenocarcinoma of the stomach.

Also distinguished are the signet ring form of gastric carcinoma, dark cell (usually quickly reaching stage g3 or 3), and invasive form of gastric adenocarcinoma (clearly manifested at stage g2 or 2).

Survival prognosis

In general, for stomach cancer, the five-year survival prognosis at different stages is as follows:

• if the cancer does not spread beyond the stomach - 68%;
• if the tumor has spread to neighboring organs or regional lymph nodes - 31%;
• if distant metastases of cancer are detected - 5%.

Signet ring cell tumors are often diagnosed at advanced stages and have a poor prognosis. In each specific case, this issue should be discussed with the attending oncologist individually.

Gastric adenocarcinoma - what is it and how to deal with it

The most common type of cancer of the digestive system is gastric carcinoma (cancer), which requires mandatory treatment. Gastric adenocarcinoma is an oncology in which a malignant neoplasm develops in the mucosal epithelium. The location of tumor formation is variable: it can appear in different parts of the stomach. Anything can have an adverse effect on its development - an ulcer, gastritis, duodenal disease. Typically, stomach cancer occurs in men and in older age.

Prevention

Since the exact causes of this type of cancer are unknown and the risk factors are not well understood, there are no specific methods for preventing the disease. In order to reduce the likelihood of developing cancer, doctors recommend generally following a healthy lifestyle:

• Exercise daily.
• Try to include vegetables and fruits in your diet.
• Avoid smoked and salty foods.
• If you smoke, get rid of the bad habit.
• Maintain a healthy weight.

Screening helps to detect a malignant tumor in the early stages, while there are no symptoms yet. People at high risk are advised to undergo gastroscopy periodically. This study is being conducted at a European clinic. Here, it is performed by experienced medical specialists using modern expert-class equipment.

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