Gastrointestinal Stromal Tumour (GIST)

Introduction

Gastrointestinal stromal tumours are abbreviated as GISTs (pronounced “jists”). These tumours start in the specialized cells of the gastrointestinal (GI) tract and differ from other cancers of the GI tract.

The gastrointestinal system

The gastrointestinal tract or the digestive system is composed of many organs. Its primary purpose is the digestion and absorption of food. These organs include the oesophagus, stomach, colon, rectum, appendix, liver, bile duct, gallbladder and pancreas. They also carry out several other functions.

GIST and other cancers

Most cancers arise from the glands in the inner lining of the GI tract. These are adenocarcinoma or squamous cell carcinoma. GISTs arise from the special cells in the wall of the GI tract called the interstitial cells of Cajal. GISTs start when some of these cells grow uncontrolled and form a tumour. GISTs can grow and spread like other cancers, though there are many differences.

Location

GISTs most commonly arise in the stomach, followed by the small intestine, but can occur anywhere along the GI tract. Sometimes they also occur outside the GI tract in the omentum and peritoneum. They are more common in individuals older than 50 years.

Causes of GIST

Genetic changes in the cells cause GIST. These changes called mutations, affect the DNA of the cells. The mutations in the KIT gene and PDGFRA gene cause most GISTs. These changes lead to uncontrolled growth of cells resulting in tumour formation.

GISTs could be sporadic or familial. Sporadic means the tumour arises in an individual without a family history. The mutations occur during the lifetime of the affected individual. Those with the familial form of the disease will have a family history of GIST. These individuals inherit a defective gene. Those with sporadic gist will usually have a single tumour, and those with familial gist will have multiple tumours.

Signs and symptoms of GISTs

Symptoms of GISTs depend on their location in the GI tract. These symptoms include.

• Abdominal pain
• Abdominal discomfort
• Nausea and vomiting
• Difficulty in swallowing (dysphagia)
• Blood in vomitus (hematemesis)
• Black stools (melena)
• Unexplained weight loss
• Loss of appetite
• Weakness
• Low haemoglobin (anaemia)

However, many patients will not have any symptoms and the GIST is diagnosed when an endoscopy or a scan is done for evaluation of some other illness.

Diagnosis of GIST

Diagnosis means identifying a disease. Following tests will help us make the diagnosis of GIST.

Physical history and examination: Understanding symptoms and checking for signs by a physician are basics of arriving at a diagnosis.

Blood tests: Complete blood count measures the distinct cells in the blood. Some patients have low haemoglobin (anaemia). Besides, liver and kidney function tests assess the function of these organs.

Upper GI endoscopy: It is a procedure in which a flexible thin tube with a camera sees the stomach from inside. Upper endoscopy will show a mass or a bulge inside the stomach. The inner lining called mucosa is normal.

Computed tomography (CT) scan: CT Scanner acquires images of the inside of our body with the help of x-ray beams. These images are then computer-processed, giving an accurate representation. Contrast injected into the blood enhances these images. A CT scan will show us the tumour and its extent.

Magnetic resonance imaging (MRI): Instead of x-rays, it uses radio waves, and strong magnetic fields.

Positron emission tomography (PET) scan: Cancer cells take up a larger amount of glucose. Here injected radioactive glucose (18F-fluorodeoxyglucose; FDG) binds to the tumour, and the patient is scanned. The images are computer-processed and combined with CT images, giving us a CT image with bright coloured tumours.

Endoscopic ultrasound (EUS): It is an ultrasound of the stomach from inside. It shows us the layers of the stomach and is useful to see tumours in the stomach's wall. It identifies the layer from which the tumour has originated and how far it has spread into the layers of the stomach and the adjacent lymph nodes. EUS can also sample cells from the tumour (FNAC - Fine Needle Aspiration Cytology) to confirm the diagnosis if required.

Biopsy or cytology: On endoscopic examination, any abnormality is sampled and examined under a microscope confirming the diagnosis. Since the inner lining is usually normal, biopsy or FNAC (sampling of a few cells) is done with the help of EUS. Since most of these tumours are operated on, biopsy or FNAC is routinely not required.

To diagnose GIST, besides examining the cells under the microscope, more tests are required. These are called immunohistochemistry (IHC). IHC tests for specific markers or antigens on tumour cells. The markers for GIST include c-kit proto-oncogene (CD117), smooth muscle actin, CD34, desmin, S-100, PDGFRA and DOG1.

Staging of GIST

The cancer cells break away from the primary tumour and spread through the body in one of the three ways; a) bloodstream, b) lymphatic system or c) directly through the tissue.

The spread could be; local, through the layers of the GI tract, to the adjacent lymph nodes and the nearby organs. Or, the spread could be distant, to the liver, lungs and the peritoneal lining of the abdomen. GIST rarely spread to lymph nodes. The distant spread is metastasis.

Staging is finding out the extent of the disease.

After the diagnosis of GIST, we do tests to find out how much the tumour has spread. Depending upon the suspected extent of the disease, some of the following investigations will be done to determine the exact stage.

• CT scan
• MRI
• PET scan
• EUS

This work-up will help us assign a stage to the tumour, broadly classifying them into:

1. Localised - Tumour is limited to the organ in which it started.
2. Regional spread - The tumour has spread to nearby lymph nodes and/or has come out of the wall of the organ in which it started.
3. Distant spread - The tumour has spread to organs, which are away from the organ of origin of the tumour, called metastasis.

TNM (Tumour, Node and Metastasis) classification

The extent (size) of the tumour (T): What is the size of the tumour?

The spread to nearby lymph nodes (N): Has cancer spread to nearby lymph nodes? And to how many?

The spread (metastasis) to distant sites (M): Has cancer spread to distant lymph nodes or distant organs such as the liver or lungs?

Grade (Mitotic rate): mitotic rate is an indicator of how fast the cancer cells are dividing and growing. Based on the number of mitoses observed under the microscope, these tumours are divided into:

• Low: 5 or fewer mitoses per 5 mm² (equivalent to 50 HPF)
• High: More than 5 mitoses per 5 mm²

Numbers and letters after T, N and M give further details. Higher the number, the more advanced the tumour. Combined Information from T, N, M, grade and location of the tumour in the GI tract assigns an overall stage, a process called stage grouping. This is called American Joint Committee on Cancer (AJCC) staging. The GIST stage ranges from I to IV. Chances of recovery from cancer (prognosis) depend on the stage of the disease at the time of diagnosis. The lower the stage, the better is the long-term prognosis.

National Institutes of Health (NIH) and Armed Forces Institute of Pathology (AFIP) classification

They divide GISTs into 4 groups

1. Very low risk
2. Low risk
3. Intermediate risk
4. High risk

Treatment

Treatment will depend upon the stage of tumour and fitness of the patient to undergo a major surgical procedure.

Treatment of localized disease - Surgery

When the GIST is localized to the organ, it originated from and has not spread to other parts of the body; it is surgically removed. The tumour along with some adjacent healthy tissue is removed.

For stomach GISTs, depending on tumour size, resection can include wide local excision, enucleation, sleeve gastrectomy, or total gastrectomy, with or without en bloc resection of adjacent organs. Similarly, for GISTs arising from other organs are operated, removing part of the involved organ. In surgery for GIST, adjacent lymph node removal is not required, as lymph node metastases are rare.

There are two ways to do these surgeries;

• Open, and
• Laparoscopic or Robotic

In open surgery, a single long incision is made over the abdomen to do the surgery.

The laparoscopic approach uses minimally invasive techniques to do the same surgery with tiny incisions. This entails the insertion of special long thin surgical tools through these small holes. This results in faster recovery and reduced pain compared to conventional open surgery. This requires expertise. Make sure your surgeon is skilled and has done many of these operations.

Targeted therapy

Substances that identify and attack cancer cells without harming normal cells.

Tyrosine kinase inhibitors (TKIs) block the signals which make the cancer cells grow. The commonly used TKIs in GIST include Imatinib, Sunitinib and Regorafenib. These are used after surgery to decrease the chances of recurrence. They are also used when the tumour has grown too big locally. TKIs can shrink these tumours and increase the chances of successful surgery. In patients where cancer has spread (metastatic), TKIs can keep the tumour in control and prolong life.

Prognosis

The survival rates after surgery are better than other cancers of the stomach. Overall recurrence rates are approximately 40%. The exact rate depends on the stage of the disease. Earlier the stage, lesser the chance of progression.

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Wish you a speedy recovery!