What is a gastrointestinal stromal tumour?
Gastrointestinal stromal tumours (GIST for short) are a rare disease of the soft tissues (sarcomas) in the gastrointestinal tract, which affects approximately 1,500 people in Germany every year. Gastrointestinal stromal tumours account for less than one per cent of all tumours in the gastrointestinal tract and were only identified as an independent type of cancer a few years ago. With almost 50 to 70 per cent, a GIST develops most frequently in the stomach (gastro). however, 30 per cent of gastrointestinal stromal tumours develop in the small intestine (intestinal). Gastrointestinal stromal tumours occur even less frequently in the large or duodenum or in the oesophagus. In half of all patients diagnosed with gastrointestinal stromal tumours, metastases are also found. These metastases are often found in the liver or in the abdominal cavity (peritoneum). More rarely, metastases have also formed in the lungs or in the bones.
How does a GIST develop?
Doctors blame a gene mutation in the cells of the gastrointestinal tract, the so-called Cajal cells, for the development of gastrointestinal stromal tumours. This genetic defect is caused by an altered protein, the so-called KIT receptor or CD117. The protein, which is located on the surface of the cells, transmits signals to grow inside the cell. In this way, the cells constantly grow and divide in an uncontrolled manner. This in turn has the consequence that neighbouring tissue is destroyed. In 1998, the Japanese pathologist Seiichi Hirota succeeded for the first time in clarifying these connections, which play a momentous role for treatment. Before a therapy can be determined, the treating physician must first determine which mutation affects the defective gene within the scope of a mutation analysis.
How exactly this genetic change arises or which risk factors need to be avoided has not yet been clarified beyond doubt by physicians. However, there are patients in whom gastrointestinal stromal tumours occur more frequently in the family.
What are the symptoms of a gastrointestinal stromal tumour?
In the early stages, GIST usually causes few symptoms, which is why the tumour is usually quite large before it is discovered. Whether and when the tumour causes symptoms depends on both its size and its location. If the GIST is in the stomach or duodenum, many patients complain of rather unspecific symptoms such as pain, nausea and/or anaemia. Anaemia can be caused by bleeding in the gastrointestinal tract. If the GIST is in the small intestine, on the other hand, people often complain of pain, bleeding or constipation. Constipation is particularly common with larger tumours. A gastrointestinal stromal tumour that is located in the oesophagus, on the other hand, can cause difficulties in swallowing.
These generally rather non-specific symptoms for gastrointestinal stromal tumours make it unlikely that a GIST will be detected early. Often, therefore, the tumour is diagnosed within an emergency operation, or within a routine operation or examination. However, modern pathology is now also able to detect the genetic defect responsible for the GIST on the surface of the cells using a special stain. However, in order to give cause for such an examination, there must often first be a suspicion of a GIST.
How is a gastrointestinal stromal tumour treated?
Until 2000, gastrointestinal stromal tumours were usually removed completely by surgery. This approach was due in part to the fact that chemotherapy is usually ineffective for this rare tumour. However, since 2002, the drug imatinib has also been used for the treatment of patients in whom the GIST has already formed metastases. It acts directly on the genetic defect and is supposed to stop the uncontrolled cell division. This targeted therapy is used over a very long period of time and must not be interrupted, as this would otherwise cause the disease activity to increase. Patients who have had their gastrointestinal stromal tumours completely removed are also given preventive treatment with imatinib after surgery to minimise the risk of relapse.
Since 2006, another drug, sunitinib, has been available for the treatment of GIST. In addition to acting on the uncontrolled cell growth, the active substance also intervenes in the signalling chains and is thus supposed to stop the production of the cancer cells. Since sunitinib can cause some undesirable side effects, close monitoring by experienced doctors is essential.
Patients who have already been diagnosed with advanced GIST can be treated with a third drug, called regorafenib. Although this drug is not yet available in Germany, it can be ordered from international pharmacies.
What are the chances of curing a GIST?
The risk of developing GIST again depends on the size of the tumour, but also on the number of mitoses/50HPF. Doctors use the term mitoses to refer to the cell division figures. These are differentiated by the pathologist into 50 visual fields (HPF), which become visible under the microscope. The HPFs provide information about the growth propensity of the tumour. In addition, the mutation must also be taken into account with regard to the risk of relapse.