Gastric cancer

Gastric adenocarcinoma accounts for 95% of gastric cancers. It’s a cancer of elderly, mostly men, and it’s the fifth most common cancer worldwide. It is more common in Asian countries like Japan and Korea, as well as certain regions in Africa and South America.

It causes no or only nonspecific symptoms in the early stages. If diagnosed early, the prognosis is excellent, but at the time of diagnosis, 50-75% of cancers have already spread and are incurable, which leads to a poor prognosis overall.

The mortality of this cancer is higher in the countries with low prevalence because screening is not performed as often as in high-prevalence countries. Therefore, the cancer is often discovered too late.

Other types of gastric cancer are described at the end of the article.

Etiology

• H. pylori gastritis or other atrophic gastritis
• Diet rich in nitrates or salts
• Alcohol
• Nicotine use
• Epstein-Barr virus
• Gastric adenomas
• Previous partial gastric resection

Plant-based diet is protective against gastric cancer.

Pathology and classifications

95% of cases of gastric cancer are adenocarcinomas. The carcinoma is usually located in the antrum, followed by corpus and fundus.

We distinguish “early” and “advanced” gastric cancer. Per definition, “early” gastric cancer infiltrates no deeper than the submucosa but even early cancer can give metastasis to the lymph nodes, while “advanced” cancers infiltrate the muscularis propria and deeper.

Lauren classification

We can use the Lauren classification which separates the gastric cancers into intestinal and diffuse types according to their location in the stomach and their gross and histological morphology.

The intestinal type has glandular structures. It has a better prognosis than the diffuse type. This type can be classified as high grade or low grade depending on whether the glandular structures show poor differentiation or well differentiation, respectively.

The diffuse type has a special cell type called signet ring cells spread diffusely across the mucosa. These cells have their nuclei compressed on the periphery of the cell, and they have large mucin-containing vacuoles in the cytoplasm. They can be hard to find on biopsy because they’re so diffusely spread. This type is more aggressive and has a worse prognosis than the intestinal type.

Borrmann classification

Macroscopically, we can see 4 different types of gastric cancer according to the Borrmann classification:

1. Polypoid type – Protrudes into the lumen like a polyp
2. Fungative type – Protrudes and has ulcerative surface
3. Ulcerative type – Non-protruding with ulcerative surface
4. Diffuse growth type – Diffusely thickened gastric wall (linitis plastica)

Linitis plastica is the end-stage of diffuse type gastric cancer, where the entire stomach is affected by the cancer. This leads to a rigid, non-distensible, “leather bottle-like” stomach.

Metastatic spread

Gastric adenocarcinoma often spreads to skeleton, liver, lung, brain, and the peritoneum. The Virchow lymph node, the left supraclavicular lymph node, is the most common site of gastric cancer metastasis.

Diffuse type of gastric adenocarcinoma may metastasise to both ovaries (bilateral), forming a so-called Krukenberg tumour.

Clinical features

The stomach is large and spacious, meaning that the tumour may grow large before symptoms appear. Early symptoms of gastric cancer include dyspepsia and mild epigastric discomfort or pain. Later, symptoms like anorexia, early satiety, weight loss, anaemia, and nausea/vomiting.

Diagnosis and evaluation

Physical examination may reveal a tumour in the epigastrium, and an enlarged Virchow’s node (left supraclavicular lymph node). DRE may reveal positive Blumer sign. Faecal occult blood tests may be positive if the tumour is bleeding.

Upper endoscopy is the investigation of choice, as it allows for both visualisation and biopsy. After the diagnosis, CT thorax and abdomen are necessary for staging.

If peritoneal carcinosis is suspected but not visible on imaging, laparoscopy may be necessary to visualise the peritoneum and diagnose the carcinosis. Cytology may be obtained from the ascitic fluid. Molecular diagnosis is important to detect any overexpression of HER2, VEGF, or PD-L1 which is important in case of advanced cancer.

Treatment

Stages I – III are curable, with metastatic (stage IV) gastric cancer usually being incurable. Cancers located only in the mucosa or submucosa (“early” gastric cancer) may be treated endoscopically or with minimally invasive surgery.

Surgery

The standard curative surgical treatment for “advanced” gastric cancer patients is radical gastric resection with lymphadenectomy. For intestinal type gastric cancer, distal or subtotal gastric resection is performed. For diffuse type gastric cancer, total gastrectomy is necessary. Afterwards, the GI system must be reconstructed by Roux-en-Y, Billroth I, or Billroth II.

Surgery may be used palliatively as well, in cases where the tumour obstructs passage of foodstuffs, for example. A stent may be placed, the stomach may be resected, or bypass surgery may be employed.

Chemotherapy

Chemotherapy may be used neoadjuvant for downstaging (to allow for surgery with curative intent), as adjuvant therapy, and as palliative therapy. The most common regimens are FLOT and ECX.

Targeted and immunotherapy

Targeted therapy (anti-HER2 trastuzumab or anti-VEGF ramucirumab) may be used palliatively, as may anti-PD-L1 pembrolizumab.

Other gastric cancers

Gastrointestinal stroma tumor (GIST)

This type of tumor is the most common mesenchymal tumor from the interstitial Cajal-cells. It can occur anywhere in the GI-tract, but is most commonly found in the stomach, followed by the duodenum.

The C-kit gene, which encodes for a tyrosine kinase, is often mutated in the patients with GIST. The mutated tyrosine kinase becomes constitutively activated, causing nonstop activation of the downstream effects and progression to cancer.

Morphologically, the tumor can either be submucous, subserous or intramural. The submucous one is often ulcerated and polypus.

Treatment is by surgery with or without the addition of tyrosine kinase inhibitor (imatinib), a drug which blocks the mutated tyrosine kinase.

Gastric lymphomas

Lymphomas can arise in every tissue, but the stomach is the most common site of extranodal lymphoma. However, it’s still one of the rarest malignancies that you can have there. The lymphomas include:

• MALT lymphoma
• DLBCL – diffuse large B-cell lymphoma

MALT lymphoma of the stomach

MALT lymphoma is a form of marginal zone lymphoma originating from B-cells in the MALT. It’s caused by H. pylori gastritis. The bacteria secrete the endotoxin CagA that leads to B-cells proliferation and autoreactive B-cells. These events eventually lead to a lymphoma. Treatment is by treating the H. pylori infection, which causes the lymphoma to regress.

DLBCL – diffuse large B-cell lymphoma

DLBCL is more aggressive than MALT lymphoma, and can either be primary (de novo), or secondary following the transformation of a MALT-lymphoma.