Stomach cancer: researchers have discovered that cells with normal appearance can cover cancer

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A layer of cells that look like normal stomach lining on top of sites of stomach cancer can make it difficult to spot after removal of a Helicobacter pylori infection.

In a recent study, researchers from Hiroshima University have uncovered the origin of this layer of cells: it is produced by the cancer tissue itself.

Helicobacter pylori (H. pylori) is a type of bacteria that lives in people’s stomachs.

To survive the harsh environment these bacteria can neutralize stomach acid. H. pylori is the leading cause of stomach cancer, one of the most common types of cancer which can have a low survival rate.

The bacteria cause inflammation by injecting a toxin-like substance into mucosal cells that line the stomach.

This destruction and regeneration of these cells can lead to the development of stomach cancer.

In this study, Professor Kazuaki Chayama from Hiroshima University Hospital and his team found the origins of a strange layer of cells that was present on stomach cancer sites after treatment of H. pylori.

This layer, called ELA (epithelium with low-grade atypia), resembled normal mucosal cells that line the stomach and acted like a mask to hide stomach cancer. Up to now, researchers were not sure where this layer came from.

“It was very interesting scientifically to find that that cancer reoccurs even after eradicating causal bacteria,” says Chayama.

An H. pylori infection is cured after a course of antibiotics, but the infection leaves reddish depression in the stomach.

H. pylori eradication affects the regeneration of gastric mucosa.

After eradication there are many reddish depressions in the stomach; most of them are not cancer.

It is difficult to identify the ELA mucosa from amongst the regular mucosa,” explains Chayama.

Extraction methods for cancerous tissue, normal tissue, and ELA Image Credit: Hiroshima University. Image Caption: The red dotted line indicates epithelium of low grade atypia (ELA) covering the surface of gastric cancer tissue in upper image. ELA (Red) and cancerous tissues (Blue) extracted by Laser Microdissection in lower image. Credit: Hiroshima University.

The research group conducted a preliminary study on 10 patients after gastric operations and looked for this layer of cells.

The ELA cells’ DNA was intensively studied and was found to be identical to stomach cancer cells. ELA was concluded to come from the stomach cancer tissue itself.

These findings could mean that even after getting rid of H. pylori there is still a risk of stomach cancer for some patients.

Stomach cancer can be difficult to spot due to its location and the fact that the disease can progress slowly.

This is not helped by ELA that masks cancer after the causal factor is removed.

Chayama stresses that clinicians should be aware of this layer, so they don’t miss potential sites of stomach cancer and that it is important for patients to continue having check-ups even after finishing treatment for H. pylori.

Details of the findings can be found in the team’s paper, published in the Journal of Gastroenterology on June 13.


Diagnosing stomach cancer

A thorough and accurate cancer diagnosis is the first step in developing a stomach cancer treatment plan.

Your team of stomach cancer experts will use a variety of tools and tests designed for diagnosing stomach cancer, evaluating the disease and developing your individualized treatment plan.

Throughout your treatment, we’ll use laboratory tests and imaging tools to monitor your response to treatment and modify your plan when needed.

Procedures designed for diagnosing stomach cancer include:

Endoscopic procedures

These minimally invasive, outpatient endoscopic procedures allow a doctor to see inside the stomach. They include:

  • Esophagogastroduodenoscopy (EGD), also known as an upper endoscopy, is the primary test for diagnosing stomach cancer. To undergo an EGD procedure, you first receive a sedative. A gastroenterologist then inserts an endoscope (a thin, lighted tube) into your mouth. He or she passes the endoscope through your throat, down into your esophagus and stomach, and into the first part of your small intestine. The endoscope enables your gastroenterologist to see inside these organs to check for abnormalities, such as tumors, ulcers, obstructions and inflammation. He or she obtains biopsies of abnormal tissue through the endoscope. The tissue is then analyzed in the laboratory to look for signs of cancer. An EGD procedure takes approximately 15 minutes.
  • Endoscopic ultrasound (EUS) helps your gastroenterologist examine your stomach and organs, such as your pancreas, liver, gallbladder and bile duct. This test for stomach cancer uses sound waves to identify tumors and nearby lymph nodes to which the cancer may have spread. EUS allows your gastroenterologist to determine whether cancer has spread through multiple layers of your stomach, helping your doctors stage the disease and tailor your treatment plan.

Biopsy

This important diagnostic procedure may be required to determine whether cancer cells are in the stomach.

In a biopsy, a small sample of cells are taken from a tumor and analyzed by a pathologist to determine if the cells are cancerous.

Lab tests

Lab tests may be used to help diagnose stomach cancer. They include:

  • Advance genomic testing examines a tumor’s DNA to look for mutations or alterations that may be driving the growth of cancer. By identifying the mutations that occur in a cancer cell’s genome, doctors may better understand what caused the tumor and tailor treatment based on these findings.
  • Complete blood count (CBC) tests determine the numbers of the different types of cells in the blood. A CBC may help determine whether a patient has too few red blood cells, which causes anemia.
  • Liver function tests may be performed to assess the function of your liver, to which stomach cancer can spread.
  • Nutrition panel helps evaluate patients for deficiency of nutrients, such as vitamin D and iron. The test helps us identify the nutrients patients need replaced or boosted to support their quality of life.

Imaging tests

Imaging tests may be used to help diagnose and stage stomach cancer. They include:

  • CT scans are taken to reveal detailed images of your abdomen. These tests help our doctors determine where the cancer is in the stomach and whether it has spread to other abdominal organs.
  • MRI may help doctors stage stomach cancer. MRIs use strong magnetic fields and radio waves to produce detailed images. These tests also allow for greater soft tissue contrast than a CT scan.
  • PET/CT scans help doctors determine the stage of the disease and whether it has spread.
  • Ultrasound may be used if fluid is found in your abdomen. Ultrasound produces images of organs from high-energy sound waves and echoes. It may also be used to check for tumors that have spread to other organs.
  • Upper gastrointestinal series is a series of highlighted X-rays of the stomach, esophagus and the upper portion of the small intestine. This procedure may require the patient to swallow barium that enhances the X-ray images. If your doctor finds abnormal cells during this procedure, the next step may be an endoscopic procedure or another diagnostic imaging test.

More information: Kazuhiko Masuda et al. Genomic landscape of epithelium with low-grade atypia on gastric cancer after Helicobacter pylori eradiation therapy, Journal of Gastroenterology (2019). DOI: 10.1007/s00535-019-01596-4

Provided by Hiroshima University

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