Stomach cancer

Cancer of the stomach is a malignant neoplasm of the stomach, a tumor emanating from the epithelium of the gastric mucosa.

Gastric cancer is a polyethiologic disease, but it is believed that Helicobacter pylori plays a major role in its onset and development. Clinical manifestations include: loss of appetite, gastric obstruction and bleeding. It is diagnosed by endoscopy with biopsy, X-ray examination, computed tomography and ultrasound. Treatment, as a rule, surgical, chemotherapy gives a temporary improvement. The long-term prognosis is usually unfavourable.

§  Epidemiology of stomach cancer

In many countries, stomach cancer is the most common malignant tumor.

Statistically, stomach cancer accounts for about 15.5% of all malignant neoplasms and 20.8% of deaths from malignant neoplasms. In prevalence, it takes the 4th place after lung cancer, breast cancer and colorectal cancer.
Adenocarcinoma of the stomach is on the second place as the cause of death from oncological diseases in the world. In 2001, 850,000 people died of stomach cancer, including 522,000 men and 328,000 women. According to data received by the World Health Organization, the most common forms of cancer worldwide (with the exception of non-melanoma skin tumours) are lung cancer (12.3%), breast cancer (10.4%), and colon (9.4% ). Among the causes of death in cancer, the first three places are respectively lung cancer (17.8%), stomach cancer (10.4%) and liver cancer (8.8%).
There are significant geographical differences in the incidence of this disease. The highest mortality was recorded in Chile, Japan, South America and the countries of the former USSR.

Men suffer from stomach cancer 2 times more often than women.
With age, the incidence rate increases. The most striking age is after 60 years (an average of 63 years).
In recent decades, there has been a trend towards a decrease in the incidence of stomach cancer. 

§  Classification of stomach cancer

§  By localization:

§  antral part - 60-70%.

§  small curvature - 10-15%.

§  cardiac part - 8-10%.

§  on the anterior and posterior walls of the stomach - 2-5%.

§  on the big curvature - 1%.

§  at the bottom of the stomach - 1%.

§  In appearance:

§  polypous (mushroom-shaped).

§  saucer-like.

§  diffuse.

§  ulcerative infiltrative.

§  On a microscopic picture:

§  undifferentiated. Small and large cell carcinoma.

§  differentiated. Glandular cancer (adenocarcinoma), fibrotic cancer (skirr), mixed and rare forms.
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  Stages of stomach cancer

§    The first stage is a tumor up to 3 cm long, sprouting mucous membrane and submucosa. There are no metastases to the lymph nodes.

§  The second stage is a tumor with a length of more than 3 cm, but without germination in the muscle layer or tumor of any size, sprouting the muscle layer, but without affecting the serous. Stage 2A - there are no metastases to the lymph nodes. Stage 2B - single metastases (no more than 2) in regional lymph nodes.

§  The third stage is a tumor of any size, sprouting the entire wall of the stomach or passing the oesophagus or duodenum. Stage 3A - there are no metastases to the lymph nodes. Stage 3B - there are multiple metastases in the regional lymph nodes.

§  The fourth stage is a tumor that grows into surrounding organs and tissues or a tumor with metastasis to distant organs.

    Classification of TNM

    Stages of gastric cancer are established by the TNM       classification. T (tumor) - tumor (its size), N (nodulus) - nodes   (presence of metastases in the lymph nodes), M (metastasis) - the     presence of distant metastases.

        The tumor T1 penetrates into the wall up to the submucosa base.

        §  T2 tumor penetrates to the subserosal membrane.

        §  T3 tumor sprouts serous membrane.
        §  T4 tumor extends to adjacent structures.
        §  N0 - no signs of metastatic lymph node involvement.
        §   N1 - there are metastases in the perigastric lymph nodes.
§  N2 - there are metastases in the regional lymph nodes.
§  M0 - there are no metastases.
§  M1 - there are distant metastases.
§  Stage I: T1N0, T1N1, T2N0, all - M0.
§  Stage II: T1N2, T2N1, T3N0, all - M0.

§  Stage III: T2N2, T3N1, T4N0, all - M0.
§    Stage IV: T4N0M0, any options with M1.

§  ICD-10 codes§  С16 - Malignant neoplasm of stomach.§  C16.0 Malignant neoplasm of the cardia of the stomach.§  C16.1 Malignant neoplasm of the bottom of the stomach.§  C16.2 Malignant neoplasm of the body of the stomach.§  C16.3 Malignant neoplasm of the vestibule of the pylorus.§  C16.4 Malignant neoplasm of the pylorus.§  C16.5 Malignant neoplasm of small curvature of stomach, part unspecified.§  C16.6 Malignant neoplasm of large gastric curvature, part unspecified.§  C16.8 Stomach lesions that go beyond one or more of the above locations.§  C16.9 Malignant neoplasm of unspecified site.

Aetiology and pathogenesis

     Aetiology of stomach cancer

The cause of the development of stomach cancer is not completely clear.

Possible etiological factors of stomach cancer include:

§  Nature of nutrition and reception of carcinogenic substances.

§  Excess intake of table salt.

§  Casting bile into the stomach. Development of intestinal metaplasia.

§  Smoking and abuse of alcoholic beverages.

§  Chronic gastritis associated with Helicobacter pylori infection. Atrophy and dysplasia, developing against a background of chronic gastritis, are considered as precancerous changes. Helicobacter promotes the formation of receptors on cells that are sensitive to the effects of various carcinogens that enhance cell proliferation, sometimes as cancerous. Peptic ulcer is not a precancerous disease.

§  The presence of adenomatous polyps in the stomach.

§  The effect of chemical factors on the gastric mucosa.

§  The impact of physical factors on the human body - ionizing radiation.

§  Increased content of selenium in the soil.

§  Hereditary factor for stomach cancer is not sufficiently studied.

§  The standard of living of the patient. In people with a low socioeconomic standard of living, stomach cancer is found 5 times more often than in people with favourable living conditions. A number of researchers explain this fact by the fact that people with a low socioeconomic standard of living often have a distribution of Helicobacteriosis from an early age.

       Pathogenesis of stomach cancer

The pathogenesis of stomach cancer has not been studied.

To date, it is known that gastric cancer is associated with gene mutations 53, APC, k-ras. Loss of heterozygosity with high frequency is observed in the following chromosome sections: 17p (locus of p53 gene), 5q (APC gene locus) and 18q (locus of DDC gene). In gastric cancer, the mutation of the k-ras gene is relatively rare. As is known, the latter plays an important role in maintaining tumor growth, and the appearance of deletions of 17q and 18q tumor suppressor genes usually occurs in later stages and serves as a marker for malignancy and metastasis of the tumor.

                                                                                                       

  

Scheme of blood supply to the stomach.

Understanding the pattern of gastric blood supply helps to predict routes of possible hematogenous metastasis. The stomach is blood supplying the celiac artery. The left gastric artery, a branch of the celiac artery, supplies the upper right side of the stomach. The common hepatic artery divides into the right gastric artery, which supplies the lower part of the stomach, and a. gastroepiploica, which supplies the lower part of great curvature.

Knowing the characteristics of the lymph drainage from the stomach, one can foresee the ways of the possible spread of metastases along the lymphatic ways. The main way of the lymph drainage passes through the celiac axis. Small pathways of the lymphatic drain pass through the spleen region, the supragastric group of nodes, the gates of the liver and the gastroduodenal region.

Regional lymph nodes in gastric cancer are affected in 45-65% of patients, even with small stomach tumors, and the likelihood of lymph node involvement increases with increasing gastric wall infiltration. Thus, when the tumor was localized within the mucous membrane, metastasis was detected in regional lymph nodes in 1.8% of patients, in the lesion of the muscular layer - in 44.3%, and when the tumor spreads to the serous gastric lining, regional metastases are detected in 73.2% of patients . After the defeat of regional lymph nodes, retroperitoneal lesions and distant metastasis are possible. The most common are metastases in the lymph nodes of the left supraclavicular area (Virchow metastasis).

An example of the hematogenous path of metastasis is the appearance of metastases by the portal vein system in the liver (31.4%), in every third patient with secondary liver damage ascites develops.

At the same time, bone metastasis (0.8%), ovaries in women (Crookenberg's metastasis - 3.4%), peritoneum (18.2%) and other organs are possible.

According to VA Printakova (1967), the origin of some distant metastases is as follows. At the onset of the disease, the orthograde metastasis pathway usually takes place, that is, the cancer cells spread along the lymph flow. With the blocking of lymph nodes metastases of cancer appear retrograde lymphatic retrograde and metastases (through retroperitoneal lymphatic pathways - meta-stasis of Krukenberg into the ovaries, Schnitzler's metastases to the pararectal tissue, metastases to the navel along the circular ligament of the liver - the bundle of sister Mary Joseph). When parasternal lymph nodes are blocked by metastases, the lymph flowing into the upper nodes of this chain from the lower deep nodes of the neck meets with an obstacle, and in the supraclavicular lymph nodes there appear retrograde-lymphogenous metastasis of Virchow.

Clinic and complications

Specific symptoms of stomach cancer do not exist. Much in the clinical picture depends on the localization of the process and the stage of the disease. Often the disease is asymptomatic until late stages.

In stomach cancer, the following symptoms can occur:

• Pain in epigastrium.
• Dyspepsia.
• Decreased appetite right up to anorexia.
• Losing weight.
• General weakness.
• Dysphagia.
• Feeling of weight after eating.
• Regurgitation (regurgitation) while eating.
• Vomiting eaten in a few hours or on the eve of food.
• Bad smell from the mouth.
• The eructation is rotten.

In the late stages of the disease, depletion and dehydration of patients.

If you have several of these symptoms, you need to see a doctor and conduct diagnostic tests to exclude or confirm an oncological diagnosis.

Diagnostics

To suspect the presence of stomach cancer is possible in the presence of diarrhea, a decrease in the patient's body weight and worsening of the general condition. At the slightest suspicion of the disease, it is necessary to conduct an EGD with a biopsy.

Methods for diagnosis of gastric cancer

Collection of complaints and anamnesis.

Inspection of the patient. Careful palpation of the navel, supraclavicular lymph nodes (left nodes are more often affected - Virchow metastases).

Esophagogastroduodenoscopy with biopsy. The most important and obligatory study for suspected gastric cancer.

-X-ray studies of the esophagus and stomach.

-Clinical blood test. Characteristic: Anemia, acceleration of ESR .

-Ultrasound of the abdominal cavity organs. This method helps to exclude the presence of metastases in the liver.

-Radiography of the lungs. This method helps to exclude the presence of metastases in the lungs.

-Biochemical examination of blood. There may be a non-specific increase in the activity of alkaline phosphatase , AST , ALT .

-CT of the abdominal cavity.

Diagnostic laparotomy.

-Rectal examination to exclude lymph node metastases in pararectal tissue (Schnitzler metastases).

-Vaginal examination and ultrasound of the ovaries. To exclude metastatic tumors of Crookenberg.

Definition of oncomarkers in the blood. Cancer embryonic antigen (CEA) increases in 45-50% of cases. CA-19-9 increases in 20% of cases.

-Histological examination of biopsy specimens of the gastric mucosa.

In 90-95% of cases of all malignant formations of the stomach, adenocarcinoma is detected. The adenocarcinoma of the stomach is divided according to histological criteria into: tubular, papillary, mucinoid, ring-fusiform, and undifferentiated.

The second most common neoplasm is lymphoma. Gastrointestinal stromal tumors, usually classified as leiomyomas or leiomyosarcomas, are 2%.

In other cases, carcinoid (1%), adenocanthoma (1%), and squamous cell carcinoma (1%) are diagnosed.

Researchers have proposed various ways to classify stomach cancer. According to the system proposed by Lauren, gastric cancer is classified into type I (intestinal) and type II (diffuse). These two types of development of the disease manifest themselves in patients completely differently.

• I type intestinal. Expansive, epidemic, intestinal type of stomach cancer. Characterized by the presence of chronic atrophic gastritis, preserved glands function, small invasiveness and clear edges. According to Lauren's classification, it is called epidemic because it usually develops as a result of environmental factors, the prognosis is better, and there is no hereditary predisposition.
• II type diffuse. Diffuse, infiltrative, endemic cancer. It consists of scattered clusters of cells with weak differentiation and fuzzy edges. The edges of the tumor, which might appear to the clean operating surgeon and the investigating histologist, are often retrospectively found to be seeded. Tumors of the endemic type penetrate into the tissues of the stomach over a large extent. This type of tumors is probably not due to environmental influences or diet, is more likely to develop in women, and affects relatively young patients. There is a correlation with genetic factors (for example, E-cadherin), blood groups, and hereditary predisposition.

Treatment

The decision on the method of treatment is made based on the stage of the tumor and the patient's desire (some patients may prefer more or less radical therapy).

Only surgical treatment gives a noticeable effect in stomach cancer.

Auxiliary chemotherapy or combined chemotherapy, as well as radiotherapy, do not have a pronounced effect in the absence of surgical treatment.

Methods of treatmentNon-drug treatment

Patients with gastric cancer should adhere to the basics of therapeutic nutrition. 

Surgery

There are radical and palliative operations for stomach cancer. Radical are two types of operations: subtotal resection of the stomach and gastrectomy. Most often, total gastrectomy (to healthy tissues), and esophagogastrectomy with tumors of the cardia and the place of passage of the esophagus into the stomach. In tumours of the distal part of the stomach, subtotal gastrectomy is performed.

Radical operations are the removal of most or all of the stomach and adjacent lymph nodes, are justified in patients with a pathological process limited by the stomach and regional lymph nodes (less than 50% of patients). It is recommended to excise the tissue at a distance of 5 cm proximal and distal to the edge of the tumor, as the network of lymphatic vessels of the stomach is well developed and the tumor is prone to metastasis. Radical treatment is indicated by a somatically safe patient under the age of 75 years, in the absence of metastases, about 1/3 of all patients.

When resection of a localized pathological formation, a 10-year average survival rate is observed (without resection for 3-4 years). When subtotal and total gastrectomy was compared with distal gastric cancer in a randomized study, there was no significant difference in the propensity to relapse, mortality and 5-year survival.

Outcomes of radical surgical treatment

Mortality during the operation - 10%. The rates of postoperative mortality within 30 days after surgery for gastric cancer have significantly decreased over the past 40 years. According to the data of most major centers, this figure is 1-2%.

The percentage of 5-year survival after radical resection is 60-90% in patients with the first stage of the disease, 30-50% in patients with the second stage, and 10-25% in patients with stage 3 disease.

Unfortunately, only a small proportion of patients after radical operations are completely cured. Most patients experience relapses.

Types of relapses

Several studies have been carried out to study the types of relapses after surgical resection, not accompanied by chemotherapy or radiotherapy. Studies based only on physical examination data, laboratory studies and imaging survey methods usually give high rates of long-term relapses and underestimates of difficult-to-diagnose relapses. A series of repertoire studies conducted at the University of Minnesota, allows you to more accurately understand the scheme of the further development of the disease. In these studies, a surgical revision of the patients was performed 6 months after the initial operation, and the results were carefully recorded. The frequency of local recurrences was 67%. The incidence of recurrences in the stomach bed was 54% of all cases, in lymph nodes - 42%. Approximately 22% of patients had long-term relapses. Approximately 22% of patients showed signs of distant relapses. Relapses were observed, at the site of a local tumor, in the tumor bed, in regional lymph nodes and distant relapses (for example, hematogenous metastases and peritoneal seeding). Primary tumors localized at the site of the esophagus into the stomach are usually metastasized to the liver and lungs. Tumors involving the esophagus metastasized into the liver. localized in the place of passage of the esophagus into the stomach, usually metastasized into the liver and lungs. Tumors involving the oesophagus metastasized into the liver. localized in the place of passage of the esophagus into the stomach, usually metastasized into the liver and lungs. Tumors involving the esophagus metastasized into the liver

Complications of surgical treatment

In 15-20% of patients after the operation postgastrectomy disorders develop.In the early postoperative period, the following complications may occur:

• Insufficiency of anastomosis.
• Bleeding.
• Intestinal obstruction.
• Obstruction of anastomosis.
• Cholecystitis (often leading to sepsis, with no signs of local inflammation).
• Pancreatitis.
• Pulmonary infections.
• Thromboembolism.
  The late complications include:
• Dumping syndrome.
• Diarrhea.
• Ulcer of anastomosis.
• Vitamin B12 deficiency _.
• Reflux is an esophagitis.
• Disorders of bone tissue, most often osteoporosis. 

Complications of gastrectomy.

Auxiliary therapy

After the surgical treatment in order to prevent relapse, the patient is prescribed auxiliary therapy. Given the frequency of recurrence, a number of studies on adjuvant therapy have been carried out in the world.

Chemotherapy and radiation treatment are conducted according to special indications, mainly for the prevention of relapse.

Comparative data for preoperative and postoperative chemotherapy and postoperative therapy in combination with radiotherapy are inconsistent.

Auxiliary radiotherapy.

The goal of radiotherapy is to prevent local metastasis.

Moertel et al., In a randomized study of patients with gastric cancer, have shown that survival with combination therapy is significantly improved when 40 Gy (Gy) or 40 Gy radiotherapy is used with radiosensitizer 5-fluorouracil .

British researchers of stomach cancer showed a reduced risk of relapse in patients who underwent postoperative radiotherapy, compared with patients who were only surgically treated.

A significant increase in 4-year survival was found in patients with inoperable stomach cancer who received combination therapy, compared with the group of patients receiving chemotherapy alone. (18 and 6% respectively). In Mayo Clinic studies, a significant increase in survival in a group of patients who received postoperative radiotherapy with 5-fluorouracil was shown, compared to the group that did not receive adjuvant therapy (23% and 4%, respectively).

Auxiliary chemotherapy.

Auxiliary chemotherapy is used to radiosensitize and prevent systemic metastases. Separate chemotherapy is ineffective. Numerous randomized clinical trials showed no significant improvement in survival with chemotherapy in the postoperative period compared with patients who underwent only surgical treatment.

As a monotherapy or in combination, use fluorouracil (5-Fluorouracil-Ebove , Fluorouracil-LENS ), doxorubicin , cisplatin ,mitomycin .

Preoperative chemotherapy can increase tumor operability, reduce micrometastasis, determine sensitivity to chemotherapy and reduce the risk of local and systemic relapse, and improve overall survival. A European randomized study showed a significant improvement in survival in patients receiving 3 cycles of preoperative chemotherapy ( epirubicin , cisplatin, and 5-fluorouracil), followed by surgery and 3 cycles of post-operation chemotherapy compared to patients receiving only surgical treatment. In patients receiving supplementary chemoradiotherapy, there was an increase in the duration of the period without relapses (from 32% to 49%), and an increase in overall survival (41% to 52%), compared to those who did not receive adjuvant therapy.

Chemotherapy with platinum preparations. Schemes of the first row of choice:

Combination of epirubicin / cisplatin / 5-fluorouracil.

Combination of docetaxel / cisplatin / 5-fluorouracil.

Other regimens include irinotecan and cisplatin.

Combinations with oxaliplatin and irinotecan are possible .

When identifying helicobacteriosa recommended eradication therapy .

Symptomatic therapy - omeprazole ( Losec MAPS , Ultop , Omez ), ranitidine ( Ranitidine , Ranisan ), narcotic analgesics.

Treatment of inoperable tumors in the terminal stage

A large number of patients identify inoperable tumors with distant metastases, carcinomatosis, inoperable hepatic metastases, lung metastases, or infiltration of organs not subject to resection. This category of patients recommended to conduct palliative therapy. The average duration of palliative therapy is 4-18 months.

As a palliative treatment, radiotherapy reduces the incidence of bleeding, the degree of obstruction, and the severity of the pain syndrome in 50-75% of patients.

Surgical palliative therapy includes local excision, partial gastrectomy, total gastrectomy, the imposition of gastrointestinal anastomosis, in order to allow oral ingestion.

The standard scheme of palliative chemotherapy involves chemotherapy based on the use of cisplatin, but the results are poorly comforting - the average time of onset of impairment is 3-4 months and the overall survival is 6-9 months.

In 2007, Japanese clinicians obtained data on some improvement in these parameters when using fluoropyrimidine S-1 as monotherapy or in combination with cisplatin (S-1 includes 3 components: tegafur , a precursor of 5-fluorouracil, gimeracil, a fluorouracil decomposition inhibitor, oteracil (potassium oxonate) to prevent side effects from the gastrointestinal tract). At the moment, these results are being tested in studies in Europe and North America ..

  

Prognosis

The long-term results depend on the stage of the disease, the histological structure of the tumor, the nature of tumor growth and the state of the body's immune system.

Intraoperative mortality in radical surgical operations in large scientific centers is less than 3%.

5-year survival after surgery at the first stage of the disease is 87-100%, with the second - 70-80%, with the third - about 20%.

In the absence of metastases in regional lymph nodes, 5-year survival after surgery is achieved in 50-60% of patients, with metastases only in 10-20% of cases.

The average life expectancy of unoperated patients with advanced gastric cancer is about 4-5 months.

The local recurrence of stomach cancer worsens.

Prevention

In the development of gastric cancer, the role of tobacco smoking, excessive intake of salt, animal fats, nitro-containing canned foods, marinades, smoked products, a deficit in the diet of antioxidants (fruits, vegetables), and ascorbic acid (vitamin C) has been proved. In this regard, prevention of gastric cancer should provide for the exclusion of bad habits and maintenance of rational (balanced) nutrition.

Preventive measures include the eradication of Helicobacter pylori infection , as its role in the development of chronic active gastritis, intestinal metaplasia, atrophy and stomach cancer has been proven.

Diagnosis and treatment of stomach cancer in the early stages of its development should be ensured with the help of appropriate diagnostic studies (endoscopy, sighting multiple gastrobiopsia, large-frame fluorography of "healthy" persons 50 years of age). The groups of high risk include patients with precancerous diseases of the stomach, blood relatives of patients with diffuse form of stomach cancer (especially with A (II) blood group), persons over 50 with reduced gastric juice secretion.