Gastrointestinal stromal tumors

Overview: What are gastrointestinal stromal tumors?

Gastrointestinal stromal tumors are tumors that can develop in the entire digestive tract. They form most frequently in the stomach and small intestine. They are found much less frequently in the large intestine or esophagus. Doctors also abbreviate gastrointestinal stromal tumors as “GIST”. Compared to other tumor types such as breast, prostate or colon cancer, GISTs are relatively rare.

This type of tumor originates in the connective or supporting tissue of the gastrointestinal tract. GISTs are soft tissue and soft tissue tumors (sarcomas). This distinguishes gastrointestinal stromal tumors from stomach or bowel cancer. These originate from the covering tissue, i.e. the mucosal cells.

In GIST, genetic changes (mutations) in certain cells of the gastrointestinal tract, the so-called Cajal cells, play a role. The KIT gene and, more rarely, the PDGFRA gene are often mutated. If the cells degenerate, they can divide and multiply unchecked.

GIST – usually asymptomatic at first

Gastrointestinal stromal tumors often cause no symptoms for a long time and go unnoticed. Doctors often only discover GISTs when they are more advanced and have reached a certain size. In rare cases, metastases form in other organs, usually in the liver or peritoneum.

There are various treatment options for GIST. The most important therapy is surgery. We try to remove the GIST as completely as possible. However, drugs that specifically target certain characteristics of the tumor cells are also a possibility (so-called targeted therapy). In contrast to other types of cancer, chemotherapy has not proven to be sufficiently effective for GIST.

The prognosis always depends on how advanced the tumor is and whether metastases are present. This actually applies to every type of cancer. But even if metastases have formed, progression can often be slowed down and we can maintain a good quality of life.

Gastrointestinal stromal tumors – frequency and age

Gastrointestinal stromal tumors are a rare type of cancer. Experts estimate that in Europe only around 14.5 per 1 million inhabitants are diagnosed with GIST each year. For Switzerland, this means around. Most people are between 55 and 65 years old when they are diagnosed with GIST. GIST is extremely rare in children and adolescents, but in principle they can also develop the disease. Men are affected slightly more often than women.

Gastrointestinal stromal tumors: causes and risk factors

GIST originate from certain cells of the connective and supporting tissue in the gastrointestinal tract, the so-called Cajal cells. These cells are significantly involved in controlling intestinal motility (peristalsis). GISTs therefore develop in the walls of the digestive organs. These tumors usually grow in a displacing manner and do not invade other organs. Nevertheless, GIST can form metastases and spread in the abdominal cavity. The risk of this is particularly high with larger GISTs (>5cm).

The beginning of tumor development is always marked by a change in the genetic material (DNA) in a cell. This is the case with all cancers. Mutation is the name given to such a genetic change. The following processes are thought to be involved in the development of GIST:

• The genetic alteration is usually found in the so-called KIT gene, where a mutation can be detected in around 80 percent of those affected. Sometimes the change is also in a section of the genome called the PDGFRA gene. In some patients with GIST, however, neither a KIT nor a PDGFRA gene mutation can be detected (so-called wild-type GIST).
• The KIT gene provides the blueprint for a special docking site on the cell surface – the KIT receptor. It consists of proteins. It normally transmits growth signals to the inside of the cell. The work of the receptor proteins can be compared to a signal receiver in the cell, similar to an antenna. The PDGFRA gene in turn creates the building instructions for the PDGFRA receptor.
• Due to the mutation, the antennae are not assembled correctly and the receptor does not work properly. They are either permanently active or they are formed in excess.
• As a result, the cells divide and multiply uncontrollably – the tumor develops.

However, what exactly triggers the mutations and is therefore the cause of GIST is still unknown. Doctors are also not aware of any risk factors that could play a role in GIST. In other types of cancer, environmental factors or lifestyle are often involved.

Gastrointestinal stromal tumors – where they prefer to develop

GISTs can develop in various parts of the gastrointestinal tract:

• They occur most frequently in the stomach – accounting for around 50 to 60 percent.
• In 20 to 30 percent of those affected, they develop in the small intestine.
• Less frequently, they form in the large intestineor duodenum, as well as in the esophagus.
• Very rarely, they can develop in the abdominal cavity outside the gastrointestinal tract (extragastrointestinal stromal tumors = EGIST).

Symptoms: Gastrointestinal stromal tumors often go unnoticed

GISTs often cause little or no symptoms. As a result, many do not realize the impending danger that is brewing in their digestive tract. They consult a doctor late in life. The symptoms depend on where exactly in the gastrointestinal tract the tumor has formed and how large it is. Smaller GISTs, which are often discovered as incidental findings, have a very high chance of recovery if they can be completely removed. However, if metastases are already present in other organs, such as the liver or abdomen, the cure rates are significantly lower.

GIST in the stomach or duodenum: symptoms

The following signs may indicate a GIST in the stomach or duodenum:

• Pain
• Feeling of fullness
• Nausea
• Bleeding in the digestive tract
• Anemia due to bleeding and blood loss
• Blood in the stool (tarry stool): The blood is dark in color because it comes from a more distant part of the digestive tract (fresh blood is bright red).

GIST in the small intestine: symptoms

The following warning signs can occur with gastrointestinal stromal tumors in the small intestine:

• Pain
• Bleeding
• Constipation

The symptoms usually only develop when the tumor in the small intestine has already grown and impairs the patency of the intestine.

GIST in the colon: symptoms

Signs of a gastrointestinal stromal tumor in the colon can include

• Blood on the stool
• Constipation

Always visit us promptly if you experience such symptoms. We can get to the bottom of your complaints and find the cause.

Gastrointestinal stromal tumors: Diagnosis by us

The problem with GISTs is that they do not cause any symptoms for a long time and we often diagnose them late. By then, GIST is often more advanced. Sometimes we find the tumor by chance, for example during an operation or routine examination.

The diagnosis of GIST begins with a discussion of your medical history, the anamnesis. For example, we are interested in the following questions:

• What exactly are the symptoms you suffer from?
• When did you first notice them?
• How intense are the complaints? Has their strength increased?
• Do they get better or worse in some situations?
• Do you have any known diseases? If yes: Which ones?
• Are there any illnesses in your family? If yes: Which ones?
• Do you take medication on a regular basis and if so, which medication and since when?

Your answers will help us to make an initial assessment of the possible causes of your symptoms. This is usually followed by a physical examination. Among other things, we palpate the abdomen and lymph nodes.

Further diagnostic methods:

• Blood test: The blood values generally show how well the organs are functioning.
• Ultrasound examination (sonography) of the abdomen
• Endoscopy of the oesophagus, stomach and duodenum (oesophago-gastro-duodenoscopy): We advance a flexible tube (endoscope) via the mouth into the esophagus, stomach and duodenum, which is equipped with a small camera. It provides images of the digestive tract and makes changes visible.
• Colonoscopy (colonoscopy): We insert the endoscope with camera via the rectum.
• Endosonography: We produce ultrasound images during the endoscopic examination. This allows us to assess not only the surface of the digestive tract, but also deeper layers of the stomach and intestinal wall.
• Tissue sample (biopsy): We take tissue samples from the suspicious areas, which are then examined under the microscope in the pathology laboratory. This histological examination reveals whether the cells are benign or malignant.
• Molecular genetic test: It shows whether the KIT receptor protein/KIT gene (more common) or the PDGFRA receptor protein/PDGFRA gene (less common) is altered. The findings play an important role in the treatment.
• Computed tomography (CT): An X-ray examination in which radiologists produce detailed cross-sectional images – they show how far the gastrointestinal stromal tumor has spread and whether metastases are present.
• Magnetic resonance imaging (MRI = magnetic resonance examination): It works with strong magnetic fields and also provides high-resolution sectional images. This also provides radiology with information about the stage and spread of the tumor. Metastases can also be detected using MRI.
• Positron emission tomography (PET/CT or PET/MR) with FDG: This method visualizes areas in the body where the metabolism is particularly active – such as in cancer cells. Low-level radioactive substances (for GIST: FDG), so-called tracers, are used. FDG accumulates in metabolically active areas. We can recognize tumors and metastases on the images.

Some patients already have metastases when they are first diagnosed. In this case, the tumor has spread to other organs and formed cancer metastases there. The liver, peritoneum and abdominal cavity are usually affected. Less frequently, metastases develop in the lungs, bones, brain or lymph nodes.

Gastrointestinal stromal tumors: classification into stages

We classify GIST in different stages. The higher the stage, the more advanced the cancer and the less favorable the prognosis. The so-called TNM classification is internationally recognized:

• T (tumor): How large is the tumor and how far has it spread? (T1 to T4)
• N (node = lymph node): Are there cancer cells in the lymph nodes? (N0 and N1)
• M (metastases): Are metastases present in other organs? (M0 = no metastases and M1 = there are metastases)

Based on the TNM classification, the cancer is divided into stages 1 to 4 (UICC stages). The higher the number, the more advanced the cancer. The treatment also depends on this.

Gastrointestinal stromal tumors: prevention, early detection, prognosis

There are no special measures for the prevention and early detection of GIST. There are also no known risk factors for these tumors that you could address yourself to prevent them. We often find GIST by chance as part of another examination or surgical procedure.

As a general rule, always consult your doctor promptly if you experience symptoms in your digestive tract.

Course and prognosis of gastrointestinal stromal tumors

The course and prognosis of GIST cannot be generally predicted. They depend on various factors, above all the location, stage, presence of a mutation, spread, cell division rate and aggressiveness of the tumor. However, your age and general state of health also have an influence on the course and prognosis of the cancer. Even though many people diagnosed with cancer ask how long they have left to live, we do not usually make any concrete statements about this today. The lifespan can be much longer than the statistics say, but it can also be shorter.

Self-help groups

The exchange with people who are affected by the same disease can be a great support in coping with the disease. Advice on finding a suitable self-help group is available from Selbsthilfe Zürich. Self-Help Zurich and the University Hospital Zurich are cooperation partners in the national project “Health literacy thanks to self-help-friendly hospitals”.

Gastrointestinal stromal tumors: Treatment by surgery and medication

Doctors from various disciplines are involved in the treatment of gastrointestinal stromal tumors, for example oncology, surgery, pathology, anesthesiology or gastroenterology. But psycho-oncology is also playing an increasingly important role, because cancer not only affects the body, but also the mind. They all work together on an interdisciplinary basis and discuss each case individually in a tumor board.

The treatment always depends on where the tumor is located, how far it has spread and how aggressively it is growing. Existing genetic alterations – the KIT/PDGFRA genotype – also determine the choice of therapy for GIST. A mutation analysis is a prerequisite for the use of medication. In contrast to many other types of cancer, chemotherapy is not promising here.

Regular follow-up care is important for all people with cancer. This also applies if you suffer or have suffered from a GIST. We monitor your state of health, treat complaints or the consequences of the illness and detect a possible relapse. Initially, the check-up appointments are very frequent. If the tumor has not returned, the intervals become longer and longer.