Gastric adenocarcinoma of the intestinal type is a malignant tumor (gastric cancer) originating from the glandular cells of the stomach lining. It is the most common histological subtype of gastric cancer and is closely associated with environmental factors, dietary habits, and chronic infection with Helicobacter pylori (H. pylori).

Pathogenesis and risk factors

The intestinal type of gastric adenocarcinoma arises through a complex, multistep progression commonly referred to as the Correa cascade, which outlines the sequential changes in the gastric mucosa leading to malignancy. This begins with chronic gastritis, often due to H. pylori infection, which progresses to atrophic gastritis, intestinal metaplasia, dysplasia, and eventually carcinoma.

This cancer type shows remarkable geographic variation in its occurrence. It appears more frequently in regions with high rates of H. pylori infection, particularly in East Asia, Eastern Europe, and parts of South America. The risk increases significantly with age, typically appearing in patients over 50 years old.

Key risk factors include:

1. Infection with H. pylori: Chronic infection increases the risk of developing gastritis, which can lead to carcinogenesis.
2. Dietary factors: Diets high in salted, smoked, or pickled foods and low in fresh fruits and vegetables are linked to increased risk.
3. Smoking and alcohol consumption: Both are independent risk factors for gastric cancer.
4. Genetic predisposition: A family history of gastric cancer can increase susceptibility.
5. Age and gender: The condition is more common in individuals over 50 years old and shows a male predominance.

Symptoms

Early stages of gastric adenocarcinoma often present with non-specific symptoms, making early diagnosis challenging. Common symptoms include:

• Persistent epigastric pain or discomfort.
• Nausea and vomiting, sometimes with blood (hematemesis).
• Unintended weight loss.
• Loss of appetite or early satiety.
• Fatigue and feeling weak, it often happens because of anemia if you losing big amounts of blood over time.

Early stages

The early stages of gastric adenocarcinoma intestinal type often present with subtle or nonspecific symptoms, which can make early detection challenging. However, being aware of these early signs is crucial for timely diagnosis and treatment. Here are the common early-stage symptoms:

1. Indigestion or heartburn: Persistent or recurrent discomfort in the upper abdomen, often mistaken for regular indigestion.
2. Loss of appetite: A decrease in desire to eat, often accompanied by a feeling of fullness even after small meals.
3. Mild abdominal pain: Vague discomfort or pain in the stomach area, which may come and go.
4. Nausea: Feeling sick to the stomach, sometimes with or without vomiting.
5. Bloating: A sense of fullness or swelling in the abdomen.
6. Unexplained weight loss: Losing weight without trying, even when eating habits haven’t changed significantly.
7. Fatigue: Feeling unusually tired or weak, which may be due to mild anemia caused by slow, chronic blood loss.
8. Changes in bowel habits: This can include constipation or diarrhea.
9. Difficulty swallowing: Some patients may experience mild difficulty in swallowing, especially with solid foods.
10. Feeling full quickly: Satiety after eating only small amounts of food.

Advanced stages of gastric cancer

Advanced symptoms of gastric adenocarcinoma intestinal type are typically more severe and noticeable than early-stage symptoms. As the cancer progresses, it can cause significant changes in the body’s functions. Here are the common advanced symptoms:

• Severe abdominal pain: Persistent and intense pain in the stomach area that may not be relieved by over-the-counter medications.
• Significant weight loss: Rapid and unintentional weight loss, often accompanied by loss of appetite and malnutrition.
• Difficulty swallowing: Progressive difficulty in swallowing (dysphagia), which can lead to avoiding solid foods.
• Bloody stools: The presence of blood in the stool, which may appear black and tarry (melena).
• Vomiting blood: Hematemesis, or vomiting blood, which may look bright red or have a coffee-ground appearance.
• Jaundice: Yellowing of the skin and whites of the eyes, indicating potential liver involvement.
• Ascites: Accumulation of fluid in the abdominal cavity, causing swelling and discomfort.
• Severe fatigue and weakness: Extreme tiredness and lack of energy, often due to anemia from chronic blood loss.
• Palpable mass: In some cases, a lump or mass may be felt in the upper abdomen.
• Enlarged lymph nodes: Swollen lymph nodes, particularly in the left supraclavicular area (Virchow’s node).
• Bowel obstruction: Symptoms of intestinal blockage, including severe constipation, abdominal distention, and vomiting.
• Persistent nausea and vomiting: Frequent or constant nausea and vomiting that doesn’t improve with standard treatments.
• Cachexia: Severe wasting of the body, including loss of muscle mass and fat.
• Bone pain: If the cancer has spread to the bones, patients may experience bone pain, particularly in the spine, ribs, or pelvis.

These advanced symptoms indicate that the cancer has likely progressed significantly and may have spread beyond the stomach. Immediate medical attention is crucial at this stage for proper management and palliative care.

Diagnosis

Diagnosis of intestinal-type gastric adenocarcinoma involves a combination of clinical evaluation, endoscopic examination, and imaging studies:

1. Upper endoscopy (esophagogastroduodenoscopy): Direct visualization of the stomach lining and biopsy of suspicious lesions are critical for diagnosis.
2. Histopathological analysis: Examination of biopsy samples confirms the intestinal type by identifying glandular structures similar to intestinal epithelium.
3. Imaging studies: CT scans and PET/CT help stage the cancer and detect metastases.
4. Laboratory tests: Blood tests may reveal anemia, elevated tumor markers (such as CEA or CA 19-9), or signs of inflammation.

Differential diagnosis

Gastric adenocarcinoma, particularly the intestinal type, shares overlapping features with several other gastrointestinal conditions. Below are the key differential diagnoses:

1. Gastritis and Peptic Ulcer Disease
   Chronic gastritis and peptic ulcer disease caused by Helicobacter pylori infection or other factors may mimic gastric adenocarcinoma symptoms, such as epigastric pain and nausea. Endoscopy with biopsy helps distinguish these benign conditions from malignancy.
2. Gastrointestinal Stromal Tumor (GIST)
   GISTs are mesenchymal tumors of the stomach that may present similarly with abdominal pain or a palpable mass. Immunohistochemical markers like CD117 (c-KIT) can confirm the diagnosis of GIST over adenocarcinoma.
3. Lymphoma of the Stomach
   Primary gastric lymphoma, particularly mucosa-associated lymphoid tissue (MALT) lymphoma, is another differential diagnosis. While it can mimic adenocarcinoma in its presentation, lymphoma often requires distinct treatment protocols such as chemotherapy or targeted therapies.
4. Esophageal Adenocarcinoma
   When tumors are located near the gastroesophageal junction, distinguishing gastric adenocarcinoma from esophageal adenocarcinoma can be challenging. Histological examination and tumor location relative to anatomical landmarks aid in differentiation.
5. Metastatic Cancer
   Tumors metastatic to the stomach, such as those originating from the breast, lung, or melanoma, must be excluded through histopathological evaluation and immunohistochemistry.
6. Benign Gastric Polyps
   Hyperplastic or adenomatous polyps, which may occasionally harbor dysplasia, require biopsy to rule out malignant transformation or misdiagnosis as adenocarcinoma.

Classification

Classification systems help categorize gastric adenocarcinoma into distinct types based on histological, anatomical, and molecular features. These classifications guide treatment planning and prognosis.

1. Lauren classification

The Lauren classification system categorizes gastric adenocarcinoma into two primary histological subtypes, providing a framework for understanding its pathological variations:

• Intestinal Type:

Characterized by glandular formations resembling intestinal epithelium. It is associated with environmental factors like Helicobacter pylori infection, high salt intake, and smoking. It often develops in a background of chronic gastritis or intestinal metaplasia.

• Diffuse Type:

Lacks glandular structures and shows signet-ring cells. It is more aggressive, linked to younger patients, and has a poorer prognosis.

The intestinal type predominates in high-incidence regions, such as East Asia and South America, and typically affects older adults.

2. WHO classification (2022 revision)

The World Health Organization categorizes gastric adenocarcinomas into subtypes based on histological appearance:

• Tubular Adenocarcinoma: The most common subtype, forming irregular, dilated glands.
• Papillary Adenocarcinoma: Characterized by exophytic growths with fibrovascular cores.
• Mucinous Adenocarcinoma: Contains significant mucin pools (>50% of the tumor area).
• Poorly Cohesive Adenocarcinoma: Includes diffuse and signet-ring cell types.
• Mixed Adenocarcinoma: Displays features of multiple subtypes.

3. TNM staging system

The Tumor-Node-Metastasis (TNM) staging system by the American Joint Committee on Cancer (AJCC) evaluates cancer spread:

• T (Tumor): Depth of invasion into gastric layers.
• N (Node): Number of regional lymph nodes involved.
• M (Metastasis): Presence of distant metastases.

Intestinal-type adenocarcinoma frequently presents at earlier stages compared to the diffuse type, influencing prognosis.

4. Molecular classification

Advances in genomics have allowed molecular subclassification of gastric adenocarcinomas:

• Epstein-Barr Virus (EBV)-Positive Tumors: Associated with DNA hypermethylation and immune cell infiltration.
• Microsatellite Instability (MSI)-High Tumors: Characterized by defective DNA mismatch repair, conferring better prognosis and response to immunotherapy.
• Genomically Stable Tumors: Commonly associated with diffuse-type histology.
• Chromosomal Instability Tumors: Linked to intestinal-type adenocarcinoma, often with TP53 mutations.

Staging

The grading framework for intestinal-type gastric adenocarcinoma follows a precise system evaluating three key components: the extent of the primary tumor growth, lymph node involvement, and presence of metastatic spread. Let’s examine each component in detail.

Primary tumor assessment

The evaluation begins with examining the depth of tumor penetration through the stomach wall layers. The earliest detectable form presents as carcinoma in situ, where abnormal cells remain confined within the epithelial layer. As the disease advances, it progressively invades deeper structures:

1. The first level of invasion reaches the lamina propria, categorized as superficial penetration.
2. When the tumor extends into the submucosa, it represents a slightly deeper infiltration.
3. Further progression involves invasion of the muscular layer of the stomach wall.
4. More advanced cases show tumor growth through the subserosal tissue.
5. In the most severe scenarios, the tumor either breaks through the outer stomach lining or grows into neighboring organs and structures.

Lymph node involvement pattern

The assessment of lymph node involvement follows a numerical progression based on the quantity of affected nodes. A favorable scenario shows no lymph node involvement. The scale then progresses through increasing levels of node involvement: initial spread affecting one to two nodes, moderate spread involving three to six nodes, and extensive spread involving either seven to fifteen nodes or sixteen or more nodes in the most advanced cases.

Distant spread evaluation

This component uses a straightforward binary classification: either no evidence of distant spread exists, or distant metastasis has occurred, indicating the cancer has spread to remote areas of the body.

Combined stage classification

The overall disease staging emerges from combining these three components, creating a comprehensive picture of disease extent:

The earliest stage represents carcinoma in situ without any spread.

1. Stage IA: minimal wall invasion without spread.
2. Stage IB: slightly more advanced primary tumor growth or minimal lymph node involvement.
3. Stage IIA includes various combinations of deeper wall penetration and limited node involvement.
4. Stage IIB: several possible combinations of wall invasion and node involvement patterns.
5. Stage III: more extensive local disease with significant node involvement.
6. Stage IV: presence of distant spread, regardless of other factors.

This comprehensive staging system guides treatment decisions and helps predict potential outcomes for patients with intestinal-type gastric adenocarcinoma. Medical professionals use this framework to develop appropriate treatment strategies and monitor disease progression or response to therapy.

Treatment for gastric cancer of intestinal type

Treatment depends on the stage of the disease, patient’s overall health, and the feasibility of surgery:

1. Surgical resection: For localized disease, gastrectomy (partial or total) with lymphadenectomy is the primary treatment.
2. Chemotherapy: Often used in combination with surgery or as a standalone treatment for advanced cases. Common regimens include fluoropyrimidines and platinum-based agents.
3. Radiotherapy: Used in select cases to reduce tumor size or manage symptoms.
4. Targeted therapy: In cases of HER2-positive tumors, trastuzumab may be combined with chemotherapy.
5. Palliative care: For metastatic disease, the focus shifts to symptom control and improving quality of life.

Prognosis and future directions

The prognosis for intestinal-type gastric adenocarcinoma varies depending on the stage at diagnosis, with early-stage disease having a more favorable outlook. Generally, this subtype has a better prognosis than the diffuse type.

Ongoing research is focusing on improving early detection methods, developing more effective targeted therapies, and understanding the molecular basis of the disease. Advances in immunotherapy and personalized medicine approaches offer hope for improved outcomes in the future.

The prognosis for intestinal-type gastric adenocarcinoma depends heavily on the stage at diagnosis. Early detection significantly improves survival rates, with localized disease having a 5-year survival rate of up to 90%. However, advanced stages with distant metastases have a poorer prognosis, with survival rates below 20%.

The prognosis for intestinal-type gastric adenocarcinoma varies significantly based on several factors. Early detection generally associates with better outcomes, particularly when the cancer remains confined to the stomach wall. Regular follow-up after treatment includes scheduled imaging studies, endoscopic examinations, and blood tests to monitor for potential recurrence.

Prevention

Prevention strategies focus on reducing risk factors and early detection:

1. Eradication of H. pylori: Treatment with antibiotics and proton pump inhibitors can reduce progression to gastric cancer.
2. Dietary modifications: Increasing intake of fresh fruits, vegetables, and whole grains while limiting processed and salty foods.
3. Smoking cessation: Eliminating tobacco use reduces cancer risk.
4. Regular screenings: High-risk populations benefit from periodic endoscopic surveillance.

Key takeaways

1. The intestinal type of gastric adenocarcinoma develops through a stepwise process called the Correa cascade, involving chronic inflammation, atrophic gastritis, intestinal metaplasia, dysplasia, and eventual malignancy.
2. This type is strongly associated with environmental influences such as Helicobacter pylori infection, high salt intake, low consumption of fruits and vegetables, and exposure to dietary carcinogens. It is more prevalent in older individuals and regions with high gastric cancer incidence.
3. Intestinal-type gastric adenocarcinoma tends to grow as a cohesive tumor with a well-defined glandular structure. It is more likely to be detected at an early stage compared to the diffuse type, which can improve the prognosis with appropriate treatment.