What is Gastric Adenocarcinoma? Adenocarcinoma of the stomach is one of the most common types of gastric cancer, accounting for up to 95% of all malignant stomach tumors. The disease is insidious because it does not manifest in the early stages. Later symptoms include pain, nausea, and loss of appetite, accompanied by increasing weakness and weight loss.

Currently, the only radical treatment for adenocarcinoma is surgery. Radiation therapy and chemotherapy are used as supplemental treatments or when surgery is not possible.

Men are approximately three times more likely to develop adenocarcinoma than women. The average age of onset for both sexes is 55–65 years. Like other forms of cancer, adenocarcinoma remains asymptomatic for a long time. Significant symptoms usually indicate substantial tumor spread. Given the delayed medical attention, the five-year survival rate after treatment is 7–31%.

Gastric adenocarcinoma causes

The exact cause of the malignant transformation of mucosal cells is not fully understood. However, researchers have identified several factors that significantly increase the risk:

• Chronic Atrophic Gastritis: This condition accounts for up to 60% of all stomach cancer cases. The risk increases 3–5 times when the atrophic process is localized in the stomach body, 18 times in the antral region, and 90 times if the entire stomach is affected.
• Dietary Habits: High consumption of spicy and salty foods, pickles, smoked and cured meats, and fats, especially those thermally processed, are risk factors. Eating habits also play a role—overeating and insufficiently chewing food can lead to chronic trauma to the stomach lining, promoting malignant cell transformation.
• Helicobacter pylori Infection: Increases risk by 3–4 times.
• Smoking and Alcohol Abuse: Both significantly raise the risk of adenocarcinoma.
• History of Stomach Surgery: Post-surgery, the risk of developing cancer increases fourfold.
• Pernicious Anemia: A form of anemia related to the inability to absorb vitamin B12. It lowers immunity, leading to cancer development in 10% of cases.
• Immunodeficiency States: Including AIDS.
• Hereditary Predisposition: According to various studies, this increases the risk by 5–20%. Cases of hereditary stomach adenocarcinoma have been documented in scientific literature.
• Occupational Hazards: Such as exposure to nickel or asbestos.
• Stomach Ulcer: When located in the stomach body, the risk of malignancy doubles. This correlation is not observed for ulcers in the antral region.

Cancer almost always develops in already altered stomach mucosa. Precancerous conditions include:

• Polyps
• Atrophic Gastritis
• Ulcers

How it develops

The pathogenesis of gastric adenocarcinoma is not fully understood. A prevailing theory suggests that aggressive external factors damage the DNA structure of glandular cells in the gastric mucosa. These cells line the gastric pits and produce mucus and prostaglandin hormones. This DNA damage leads to mutations that transform healthy cells into malignant ones.

Initially, these aggressive factors cause inflammation in the gastric wall, which progresses to dysplasia and metaplasia. The cells begin to divide rapidly, become atypical, and alter the structure of the gastric mucosa. Essentially, dysplasia is considered a precancerous condition.

Once formed, adenocarcinoma grows either into the gastric lumen or infiltrates all layers of the gastric wall, adjacent tissues, and organs, such as the pancreas, liver, anterior abdominal wall, and the transverse colon with its mesentery. The tumor may also extend along the digestive tract, affecting the esophagus and duodenum.

Cancer cells spread through the lymphatic system and, at later stages, via the bloodstream, leading to metastases—secondary tumor sites in other organs. Gastric adenocarcinoma most commonly metastasizes to the liver, lungs, brain, and peritoneum.

Types of gastric adenocarcinoma

Adenocarcinoma is a type of stomach cancer originating from glandular epithelial cells. Histological classification is based on the structural differences of atypical cancer cells. The following types of gastric adenocarcinoma are recognized:

• Papillary: Develops from papillary epithelial cells.
• Tubular: Consists of branching epithelial growths.
• Mucinous: Forms from cells that produce mucus.
• Signet-ring cell: Features cells transformed into signet-ring shapes.

Adenocarcinoma can develop in any part of the stomach, most commonly in the pyloric region, followed by the cardiac region. Each localization is coded as follows:

• C16.0: Tumor in the cardiac section.
• C16.1: Gastric fundus.
• C16.2: Gastric body.
• C16.3: Antral region.
• C16.4: Pyloric region.
• C16.5: Lesser curvature.
• C16.6: Greater curvature.
• C16.8: Spreading beyond the listed areas.
• C16.9: With unspecified localization.

The tumor can exhibit various growth forms:

• Scirrhous adenocarcinoma: Deeply invades the gastric wall and adjacent areas.
• Ulcerative cancer: Appears as a saucer-shaped lesion with a central depression.
• Polypoid cancer: Resembles a polyp and has well-defined boundaries.

Differentiation grades

Gastric adenocarcinomas are also classified based on the degree of differentiation:

• Well-differentiated adenocarcinoma (G1): Tumor cells are highly differentiated and resemble healthy tissue. It grows slowly and, if detected early, is treatable. However, early detection is challenging, even with endoscopic examination, and late-stage detection reduces treatment efficacy.
• Moderately differentiated adenocarcinoma (G2): Tumor cells are moderately malignant, making identification with their tissue of origin difficult. It has moderate growth and malignancy.
• Poorly differentiated adenocarcinoma (G3): Tumor cells lack identifiable characteristics of any specific tissue. This is the most aggressive type, characterized by rapid growth and metastasis.

A binary classification system is often used, dividing adenocarcinomas into:

• High-grade adenocarcinoma: High differentiation level.
• Low-grade adenocarcinoma: Low differentiation level.

TNM classification

The TNM classification evaluates the spread of gastric adenocarcinoma based on three criteria:

• T: Depth of invasion by the primary tumor.
• N: Lymph node metastases.
• M: Distant organ metastases.

Localization Types

• Cardiac carcinoma: At the gastroesophageal junction.
• Gastric body adenocarcinoma: Along the lesser or greater curvature.
• Antral carcinoma: At the transition from the stomach to the duodenum.

Stages

Based on the depth of tumor invasion into the stomach wall and its spread throughout the body, four stages of gastric adenocarcinoma are identified:

1. Stage 0 or carcinoma in situ. Malignant cells do not extend beyond the epithelial layer.
2. Stage 1. The tumor penetrates the epithelium and spreads to other layers of the stomach wall but does not go beyond its boundaries.
3. Stage 2. The tumor increases in size and metastasizes to regional lymph nodes.
4. Stage 3. Adenocarcinoma invades neighboring organs (pancreas, liver) and/or metastasizes to multiple groups of lymph nodes.
5. Stage 4. Adenocarcinoma metastasizes to distant organs and lymph nodes.

Important to Understand!
The stage and degree of differentiation of a malignant tumor are not the same. For example, diagnosing G3 gastric adenocarcinoma does not necessarily mean the disease is in an advanced stage.

Gastric carcinoma signs and symptoms

A characteristic of the disease that worsens the prognosis for recovery and survival is prolonged development without clear symptoms. As long as the tumor is small, does not invade blood vessels, or disintegrate, the individual feels normal. Gastric adenocarcinoma does not immediately manifest.

• The first symptom is often rapid satiety, discomfort, and heaviness in the upper abdomen.
• Gradually, pain intensifies, leading to decreased appetite and weight loss.
• Signs of bleeding and vomiting are common in later stages.

The earliest and most nonspecific symptoms of gastric adenocarcinoma include:

• Unexplained fatigue and weakness.
• Mild discomfort in the navel or left hypochondrium.
• Changes in taste preferences.

These complaints rarely prompt people to seek medical attention, as they attribute them to ordinary fatigue.

Associated symptoms

• Loss of appetite.
• Dyspeptic phenomena — bloating, nausea, belching, a feeling of heaviness. If the tumor is large, it can block the stomach lumen, causing vomiting after meals, but this occurs in the later stages.
• Weakness and apathy.
• Pain. Typically, pain does not appear immediately but predominantly in advanced stages. At this point, it becomes constant and unrelated to food intake. Pain arises for no apparent reason and often intensifies after meals. In the later stages, it becomes so severe that it cannot be relieved with standard analgesics.

Pronounced symptoms appear when gastric adenocarcinoma reaches a large size, invades other organs, metastasizes, and begins to disintegrate. The clinical picture is determined by the tumor’s impact on the stomach and the body as a whole:

1. Reduction of stomach lumen — rapid satiety even with small amounts of food, a feeling of heaviness in the stomach, pain.
2. Intoxication from tumor breakdown products — severe weakness and fatigue, nausea, vomiting, weight loss.
3. Damage to blood vessels by the tumor — blood in vomit or stool, pallor, dizziness, weakness.

These symptoms indicate at least Stage 3 of the disease, when treatment becomes much more difficult, and the prognosis worsens.

As we can see, these symptoms are nonspecific, and people may try to manage them on their own for a long time.

Complications

1. Bleeding
   Bleeding is a common complication of gastric cancer. It occurs due to ulceration of the tumor itself, and at later stages, due to tumor disintegration. It manifests as vomiting blood or black stools (melena). If these symptoms appear, an endoscopic examination should be performed, and the bleeding must be stopped. If bleeding persists afterward, the patient requires urgent surgery.
2. Tumor Stenosis
   Tumor stenosis is the partial or complete blockage of the stomach’s entry or exit. It arises due to tumor overgrowth.
   • In cases of stenosis in the stomach’s exit region, patients experience vomiting of undigested food.
   • In cases of stenosis in the cardiac region, patients suffer from difficulty swallowing (dysphagia).
     If possible, a stent should be placed at the stenosis site. If this is not feasible, surgery is required:
   • Gastrostomy: Creating an artificial opening into the stomach cavity.
   • Jejunostomy: Diverting the jejunum to the abdominal wall.
   • Gastroenterostomy: Creating a new connection between the stomach and intestine.
     In modern practice, jejunostomy can be performed not through traditional surgery but via a puncture of the abdominal wall under ultrasound guidance.
3. Ascites
   Ascites is a medical condition characterized by the abnormal buildup of fluid within the abdominal cavity. This complication occurs due to compression of the portal vein by the tumor and/or the development of peritoneal carcinomatosis. It is accompanied by abdominal enlargement caused by fluid buildup and typically develops at stage IV of the disease.

Diagnostics

Timely diagnosis of gastric cancer is critically important since the prognosis at early stages is far more favorable than in advanced stages. However, early-stage adenocarcinoma often presents asymptomatically or with symptoms that mimic other conditions such as gastritis, ulcers, gallstone disease, or pancreatitis. As a result, patients may delay consulting a doctor and instead self-medicate using over-the-counter drugs.

Diagnostic approach

The diagnosis of gastric adenocarcinoma is comprehensive and includes a range of examinations that help identify the tumor type and disease stage:

1. Esophagogastroduodenoscopy (EGD)
   This examination uses a flexible endoscope to visually inspect the stomach lining. The endoscope transmits magnified images of the examined area to a monitor, allowing for the detection of even minor mucosal changes. Additionally, the endoscope is equipped with tools to collect tissue samples for histological analysis, which helps determine the tumor type and the degree of cellular differentiation.
2. Ultrasound (US)
   Ultrasound helps assess the size of the tumor, its relationship with neighboring organs, and the presence of metastases in regional lymph nodes.
3. CT and MRI
   These imaging modalities assist in verifying the size of the malignant tumor, its infiltration into surrounding tissues, and identifying metastases in lymph nodes and distant organs (e.g., the lungs).
4. PET-CT (Positron Emission Tomography-Computed Tomography)
   This technique detects distant metastases as small as 1 mm.
5. Tumor Markers (CEA, CA72-4, CA19-9)
   These markers are not diagnostically definitive for gastric cancer but are useful for monitoring treatment effectiveness and recurrence. Postoperative levels should decrease and may normalize. A rise in marker levels suggests recurrence or disease progression.
6. Laparoscopy
   This involves examining the stomach using a videolaparoscope. It is indicated for patients suspected of tumor invasion into the stomach’s serous membrane based on endoscopic ultrasound or CT. Laparoscopy is mandatory for total and subtotal organ involvement. If local tumor spread is confirmed, the treatment strategy changes: these patients typically undergo chemotherapy first, followed by surgery if the tumor shrinks. During laparoscopy, fluid samples from the stomach and abdominal cavity may be collected to detect tumor cells and stage the cancer before initiating chemotherapy.

Additional examinations may include:

• Blood tests for tumor markers.
• Biopsy and histological evaluation.
• Laboratory diagnostics (e.g., stool tests for occult blood).
• X-rays.
• Endoscopic diagnostics.
• Oncologist consultations.
• Oncological screening for early detection.

Initial assessment and symptoms

During the initial consultation, the doctor evaluates the nature of the patient’s complaints, their duration, and progression. Upon physical examination, signs of oncopathology may include:

• Emaciation.
• Pale-gray skin tone.
• Abdominal tenderness, particularly in the left side.

Given the nonspecific symptoms of gastric adenocarcinoma, laboratory and instrumental studies play a key role in diagnosis.

Laboratory studies

1. General Blood Tests
   These reveal a sharp increase in ESR (erythrocyte sedimentation rate) and decreased hemoglobin levels.
2. Tumor Marker Analysis
   Identifies abnormal levels of cancer-associated markers.
3. Gastric Juice Analysis
   Often shows increased acidity.
4. Stool Analysis for Occult Blood
   Detects hidden bleeding within the gastrointestinal tract.

These findings indirectly indicate malignancy in the body.

Endoscopic examination

The main method for detecting stomach tumors is fibrogastroscopy. This technique involves optical inspection of the stomach lining under magnification, enabling the detection of minimal changes and identifying tumors as small as 1–2 mm. During the procedure, tissue samples are collected for histological examination.

Histological Analysis

The laboratory examines the collected samples under a microscope, providing information on:

• The degree of cellular differentiation.
• Tumor type.
• Depth of tumor invasion into the organ wall.

This information is crucial for determining the treatment strategy.

Radiological Studies

X-ray imaging is indicated for infiltrative carcinoma growth, where the tumor spreads within the stomach wall. Contrast imaging helps determine the tumor’s depth, size, growth characteristics, and location.

Precise staging of gastric carcinoma involves identifying both regional and distant metastases through:

• Ultrasound of the abdominal cavity and supraclavicular area.
• CT scans of the chest, abdomen, and retroperitoneal space.
• Diagnostic laparoscopy.

Gastric carcinoma metastasis

• Implantation Metastasis: This involves the spread of cancer cells through direct contact between the tumor and a receptive surface. In gastric cancer, such surfaces may include the peritoneum, pleura, pericardium, and diaphragm. In advanced-stage cancer, carcinomatosis (extensive metastasis to various tissues) is often detected.
• Lymphatic Metastasis: Tumor cells spread through lymphatic vessels, initially affecting nearby lymph nodes and then more distant ones. Gastric cancer has specific forms of lymphatic metastases:
  • Virchow’s nodes: Affecting lymph nodes in the left supraclavicular area.
  • Schnitzler’s metastases: Involving pararectal lymph nodes.
  • Irish metastases: Affecting axillary lymph nodes.
• Hematogenous Metastasis: This refers to the spread of cancer cells via blood vessels. The liver is most commonly affected due to cell migration through the portal vein. Other potential sites include the lungs, kidneys, brain, and bone marrow.

Treatment

Treatment depends on the stage of the disease and the histological type of the tumor. Gastric adenocarcinoma is typically treated with a combination of surgery, chemotherapy, and/or radiation therapy, with surgery being the cornerstone of treatment.

Surgical treatment for early-stage stomach cancer

For early forms of cancer (e.g., carcinoma in situ), endoscopic treatment is indicated:

1. Endoscopic Mucosal Resection (EMR): Removal of the tumor along with part of the stomach’s mucosal layer.
2. Endoscopic Submucosal Dissection (ESD): Removal of the tumor along with part of the submucosal layer. This method is used for adenocarcinomas up to 2 cm and allows for en bloc resection without incisions.

These procedures are performed under general anesthesia. The tumor’s boundaries are first marked using electrocoagulation, with a margin of 3 mm. A saline and hydroxyethyl starch solution is then injected into the submucosal layer to separate the tumor from the muscle layer. After tumor removal, the site is checked for bleeding, perforation, and complete excision. The removed fragment is sent for histological analysis.

Postoperative Care:

• Patients are discharged on the 3rd or 4th day.
• Treatment efficacy reaches 98% when standards are followed.
• Recommendations:
  • Gastroscopy one month after surgery and every three months thereafter.
  • CT scans six months post-surgery.
  • A strict diet for one month, consisting of liquid and pureed foods, avoiding alcohol and hot meals.

Surgical treatment for advanced stages

Radical surgery, including tumor removal along with affected tissues and lymph nodes, is the most effective method. This is feasible at stages 1–2, where distant metastases are absent. At stage 4, surgery is usually contraindicated.

Types of surgery:

1. Subtotal Resection: Removal of most of the stomach and surrounding tissues.
2. Gastrectomy: Complete removal of the stomach, surrounding tissues, lymph nodes, and establishment of a gastrostomy.

The surgical approach (open or laparoscopic, including robotic-assisted methods) depends on the tumor’s size, location, and metastasis extent.

Lymph Node Dissection: Often performed to reduce the risk of recurrence, as adenocarcinoma frequently spreads via lymphatic pathways.

For patients with extensive metastases, surgery is not generally performed. However, life-saving interventions (e.g., for stomach wall perforation, bleeding, or stenosis) may be necessary.

Chemotherapy

Chemotherapy is the primary treatment for unresectable tumors, aiming to destroy cancer cells or significantly slow their growth.

Options include:

1. Monotherapy: Using a single drug.
2. Combination Therapy: Using multiple drugs for a stronger anti-tumor effect.

Combination treatments:

• Perioperative Chemotherapy: Administered before surgery to reduce tumor size and after surgery to target remaining cancer cells.
• Adjuvant Chemotherapy: Conducted post-surgery.
• Adjuvant Chemoradiotherapy: Performed when cancer cells remain at the surgical margins.

Indications for Chemotherapy:

• Tumor invasion beyond the mucosal layer.
• Lymph node involvement.
• Presence of metastases.

Patients may decline chemotherapy but should understand the risk of rapid tumor recurrence and metastasis without treatment.

Palliative care and symptomatic treatment

Palliative care focuses on improving the quality of life for stage IV cancer patients when specific treatments are not feasible. This includes adequate pain management.

• Pain relief progresses from mild analgesics (e.g., ketoprofen) to stronger drugs (e.g., tramadol, morphine), administered every four hours for severe pain.
• Palliative surgical interventions, such as bypass anastomosis or gastrostomy, may be performed to alleviate complications like gastric obstruction.

Prognosis and survival rates

The prognosis for gastric adenocarcinoma depends on the morphological type of the tumor (differentiation), its size, the presence and number of metastases, as well as invasion into surrounding organs.

Often, patients with adenocarcinoma consult a doctor only in the later stages of the disease, when the tumor presents with complications and can no longer be removed. This delay occurs because early symptoms of cancer resemble those of gastritis or stomach ulcers. Patients may not feel the urgency to undergo gastroscopy and instead opt to purchase over-the-counter medications, which temporarily alleviate symptoms while the tumor continues to grow.

As a result, the prognosis for gastric adenocarcinoma is often unfavorable. However, the earlier the treatment begins, the more effective it will be:

• Stage I: Five-year survival reaches 80%. There is a high chance of complete recovery. Unfortunately, this stage of stomach cancer is rarely detected, usually by chance.
• Stage II: Five-year survival approaches 55%. Half of these patients have a chance of complete cure. According to the literature, fewer than 10% of malignant stomach tumors are identified at this stage.
• Stage III: Five-year survival is less than 40%, while for Stage IV, it does not exceed 5%. Unfortunately, up to 75% of adenocarcinomas are diagnosed at Stage IV.

Gastric Adenocarcinoma Prevention

The prevention of gastric cancer focuses on avoiding or reducing exposure to risk factors that contribute to the development of the disease:

• Dietary normalization: Ensure adequate intake of dietary fiber (vegetables, fruits, grains) while limiting salt, spices, marinades, and smoked foods.
• Avoid smoking and excessive alcohol consumption.
• Treat infections and precancerous conditions such as chronic gastritis and stomach polyps.
• Maintain adequate levels of physical activity.

Can gastric cancer be cured?

Gastric cancer (stomach cancer) can be cured, but the likelihood of a complete cure depends on several factors, including the stage of the cancer, the patient’s overall health, and the treatment approach.

Factors Influencing Cure:

1. Early Diagnosis:
   • When gastric cancer is diagnosed at an early stage (Stage I or II), the chances of a complete cure are significantly higher.
   • In these cases, surgical removal of the tumor combined with chemotherapy or targeted therapy can lead to long-term remission.
   • Five-year survival rates for Stage I gastric cancer can reach 70-80% or higher.
2. Advanced Stages:
   • In later stages (Stage III or IV), a cure is less likely, as the cancer may have spread to nearby lymph nodes or distant organs.
   • Treatment at these stages focuses on managing symptoms and prolonging life rather than achieving a cure. However, advancements in chemotherapy, immunotherapy, and targeted therapies have improved outcomes for some patients.
3. Type and Location of the Cancer:
   • Certain types of gastric cancer (e.g., well-differentiated tumors) respond better to treatment.
   • Tumors localized in the stomach (without significant spread) are more amenable to curative interventions.
4. Comprehensive Treatment:
   • Surgery: Complete surgical removal (gastrectomy) of the tumor is the cornerstone of treatment for localized gastric cancer.
   • Chemotherapy/Radiation Therapy: Used before or after surgery to shrink tumors or kill remaining cancer cells.
   • Targeted Therapy/Immunotherapy: For advanced stages, these newer treatments can sometimes prolong survival significantly.

Key Takeaways