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Diagnosing neuroendocrine cancer

Diagnosis is the process of finding the underlying cause of a health problem. The process of diagnosis may seem long and frustrating, but it is important for the doctor to rule out other possible reasons for a health problem before making a cancer diagnosis. Diagnostic tests for neuroendocrine cancer are usually done when:

  • the symptoms of neuroendocrine cancer are present
  • the doctor suspects neuroendocrine cancer after talking with a person about their health and completing a physical examination
  • routine or screening tests suggest a problem with the lungs, intestine, pancreas or other organs in which the cancer may be present

Many of the same tests used to initially diagnose cancer are also used to determine the stage (how far the cancer has progressed). Your doctor may also order other tests to check your general health and to help plan your treatment. Tests may include the following:

Medical history and physical examination

The medical history is a record of present symptoms, risk factors and all the medical events and problems a person has had in the past. The medical history of a person's family may also help the doctor to diagnose neuroendocrine cancer.

In taking a medical history, the doctor will ask questions about:

A physical examination allows the doctor to look for any signs of neuroendocrine cancer. During a physical examination, the doctor may:

  • measure the pulse, blood pressure, heart rate and respiratory rate
  • examine the airways (the path that air follows to reach the lungs) and lungs for abnormal breath sounds, decreased air entry or other changes that may indicate the presence of a tumour 
  • feel the abdomen for tenderness, enlarged organs or lumps
  • examine the heart for any abnormality

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Blood chemistry tests

Blood chemistry tests measure certain chemicals in the blood. They show how well certain organs are functioning and can also be used to detect abnormalities. They are used to diagnose and stage neuroendocrine cancer.

  • Blood glucose levels may be abnormal if a pancreatic neuroendocrine tumour produces hormones such as glucagon or insulin.
  • A stomach acid test measures the amount of acid produced in the stomach. This output is increased in gastrinomas, which produce too much of the hormone gastrin.
  • High levels of specific hormones, such as insulin, glucagon, gastrin, vasoactive intestinal polypeptide (VIP) or somatostatin, may help doctors to diagnose neuroendocrine tumours.

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Tumour marker tests

Tumour markers are substances – usually proteins – in the blood or urine that may indicate the presence of neuroendocrine cancer. Tumour marker tests are used to check a person's response to cancer treatment, but they can also be used to diagnose neuroendocrine cancer.

The tumour markers that may be measured are:

  • Chromogranin A (CgA) is the most important circulating tumour marker for neuroendocrine tumours. CgA levels are higher in 60%–80% of functional and non-functional gastrointestinalgastrointestinalReferring to or having to do with the digestive organs, particularly the stomach, small intestine and large intestine. and pancreatic neuroendocrine tumours. False-positive results for this marker (the test is positive but CgA is not present) may be caused by:
    • poor kidney function
    • chronic atrophic gastritis (changes in the stomach lining)
    • proton pump inhibitors (PPI) (medicine given to reduce stomach acid)
  • 5-hydroxyindoleacetic acid (5-HIAA), a product of the breakdown of serotoninserotoninA type of neurotransmitter (a chemical that transmits signals or impulses from one neuron, or nerve cell, to another neuron cell or other specialized cells) that causes blood vessels to narrow and regulates the movement of the intestines., is a specific marker for some neuroendocrine tumours that produce serotonin. 5-HIAA levels are measured in 24-hour urine samples.
    • Various foods and drugs, including bananas, avocados, cough syrup, acetaminophen (Tylenol, Atasol), aspirin and caffeine may cause false-positive results (the test is positive but 5-HIAA is not present).
    • Glucocorticoids (steroids produced in the adrenal gland that affect the metabolism of carbohydrates, fats and proteins) and heparin (an anti-clotting medication) may cause false-negative results (the test is negative but 5-HIAA is present).
  • The levels of specific hormones released by functional or hormone-producing neuroendocrine tumours and carcinomas are used as tumour markers. For example, insulin levels may be used for a marker of insulinoma and gastrin levels may be used to detect gastrinoma.

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An x-ray uses small doses of radiation to make an image of the body's structures on film. A chest x-ray may help to detect tumours in the lung.

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Ultrasound uses high-frequency sound waves to make images of structures in the body. A special procedure called endoscopic ultrasound is used to find and assess neuroendocrine tumours or carcinomas in the respiratory and upper digestive (aero-digestive) system. In this procedure, a device that produces ultrasound waves is placed in the upper digestive tract. Doctors look at the image produced to see if the lymph nodes are enlarged or if there are tumours present.

Ultrasound may be used during surgery to find very small pancreatic neuroendocrine tumours. This surgical technique uses an ultrasound probe inserted into the abdomen through an incision.

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Computed tomography (CT) scan

A CT scan uses special x-ray equipment to make 3-dimensional and cross-sectional images of organs, tissues, bones and blood vessels inside the body. A computer turns the images into detailed pictures. It is used to:

  • detect neuroendocrine cancers and metastases in the liver, mesentery (tissue that attaches organs to the body wall) or other nearby structures
  • guide a fine needle aspiration biopsy to get a tissue sample

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Magnetic resonance imaging (MRI) scan

An MRI scan uses powerful magnetic forces and radio-frequency waves to make cross-sectional images of organs, tissues, bones and blood vessels. A computer turns the images into 3-dimensional pictures. MRI scans may be used if ultrasound and CT images do not give doctors enough information to make a diagnosis.

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Octreotide scan (OctreoScan) 

Somatostatin is a peptide that binds to somatostatin receptors on neuroendocrine tumour cells. Somatostatin prevents the neuroendocrine cells from producing hormones by blocking these receptors. Because somatostatin has a short half-life (1–2 minutes), long-acting drugs with the same action (congeners) have been manufactured. Octreotide (Sandostatin) and lanreotide (Somatuline) are somatostatin congeners that are used to diagnose and treat neuroendocrine tumours.

For scanning, octreotide is labelled with radioactive tracers and injected into a person. The radiation patterns are recorded through a scan using a special camera that produces images of the targeted neuroendocrine tumours and any metastases. This procedure is known as somatostatin receptor scintigraphy (SRS). It is called an octreotide scan or OctreoScan when a radiolabelled form of octreotide is used.

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Metaiodobenzylguanidine (MIBG) scan

MIBG is a substance that is selectively taken up by neuroendocrine cells in the adrenal medulla and paraganglia. It can be used to scan for neuroendocrine tumours that develop in these structures. MIBG is attached to radioactive iodine (I-123 or I-131) and injected into a vein. Several hours or days later, the body is scanned with a special camera to map the areas of radioactivity.

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Positron emission tomography (PET) scan

A PET scan uses radioactive materials (radiopharmaceuticals) to detect changes in the metabolic activity of body tissues. A computer analyzes the radioactive patterns and makes 3-dimensional colour images of the area being scanned.

PET scans usually use a radiolabelled glucose (a sugar with radioactive material attached) because it builds up in higher concentration in rapidly dividing cells. This type of PET scan is not very useful for neuroendocrine tumours because they generally have a low metabolic rate (except tumours that are poorly differentiated and aggressive). Therefore, a radioactive form of 5-hydroxytryptophan (5-HTP) that is attracted to specific receptors on the neuroendocrine tumour cells is used. The PET scan produces an image of the tumour cells that actively metabolize (process) the 5-HTP radioisotope.

Advanced imaging techniques that combine PET and CT scans are being used in some specialized centres. This technique is called PET-CT scan. The functional image of a PET scan is combined with the structural image of a CT scan. A PET-CT scan image gives healthcare professionals more and better information about how much hormone-producing tumour tissue is present in a particular area of the body.

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Bone scan

A bone scan uses bone-seeking radioactive materials (radiopharmaceuticals) and a special camera connected to a computer to create a picture of the bones. It is used to find areas with greater or less uptake of the radioactive material. Areas of bone affected by metastases may show up as "hot spots" or "cold spots" on the scan.

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Endoscopic procedures

Endoscopy is done to look for any masses in the lining of the digestive tract. It allows a doctor to look inside body cavities using a flexible tube with a light and lens on the end (an endoscope). If any abnormality is found, a biopsy is taken for examination under a microscope to rule out or confirm cancer.

Depending on the area of the body being viewed, the endoscope can be passed through the mouth or anus, or through a small cut or incision in the body. Instruments can be inserted through a channel in the endoscope to remove small pieces of tissue. Cameras can be attached to some endoscopes to display images on a screen for the doctor to see. An endoscopy can usually be done on an outpatient basis, but sometimes the person may need to stay in the hospital overnight. Drugs are usually given to help the person relax during the procedure.

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Esophageal endoscopy

This is an endoscopic procedure that allows the doctor to see inside the esophagus, stomach and first part of the small intestine (the duodenum).

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Endoscopic retrograde cholangiopancreaticography (ERCP)

ERCP is a procedure that allows a doctor to view the gallbladder and pancreas, as well as the bile, cystic and pancreatic ducts. It is helpful in determining if any of the ducts are blocked.

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A colonoscopy is a procedure that lets the doctor look at the lining of the colon beyond the rectum and lower part of the colon. A colonoscopy is preferred over a flexible sigmoidoscopy because the entire colon can be checked for polyps or abnormal areas.

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Flexible sigmoidoscopy

A flexible sigmoidoscopy is a procedure that lets the doctor look at the lining of the rectum and lower part of the colon (sigmoid colon). A sigmoidoscopy can be done in a doctor's office or clinic. The doctor passes the endoscopeendoscopeA thin, tube-like instrument with a light and lens used to examine or treat organs or structures in the body. through the anus and slowly moves it into the rectum and lower part of the colon. This can be uncomfortable, but not painful. Drugs for relaxation and pain relief are usually not needed.

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Capsule endoscopy

Neither upper nor lower endoscopy can reach all areas of the small intestine, which may allow small intestinal tumours to go undiagnosed or delay their diagnosis. A capsule endoscopy can help a doctor examine the small intestine in greater detail. The person swallows a capsule (the size of a large pill) that contains a light source and a tiny camera. The capsule goes through the stomach and into the small intestine, taking thousands of pictures as it travels. These images are sent electronically to a storage device that the person wears. The doctor views these pictures on a computer as a video. During a capsule endoscopy, people can go about their normal daily activities. The capsule is passed during a normal bowel movement and discarded.

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Double balloon enteroscopy

It is difficult to examine the small intestine because it is long and has many curves. A double balloon enteroscope can be used to examine the entire small intestine. This special endoscope has an inner and outer tube equipped with inflatable balloons. This procedure is usually done under general anesthesia. Unlike a capsule endoscopy, this procedure allows doctors to take a biopsybiopsyThe removal of cells or tissues for examination under a microscope. of any abnormal area they see.

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A bronchoscopy is a procedure used to look inside the trachea (windpipe) and bronchi (large airways of the lungs). It is also used to remove foreign bodies, perform biopsies, control hemoptysis (coughing up blood), collect bronchial washings and remove masses in the airway.

An instrument called a bronchoscope is passed into the bronchial tubes of the lungs. The bronchoscope may be rigid or flexible. The rigid bronchoscope is passed through the mouth into the bronchial tubes. It is used in procedures that require greater access into the lungs, including to control bleeding and to remove foreign bodies or tumours in the lungs. Rigid bronchoscopy is used much less often than flexible bronchoscopy.

The flexible bronchoscope is a flexible fibre optic bundle. It transmits an image from the tip of the bronchoscope to a camera, which allows doctors to visualize the bronchi. Doctors can use the flexible bronchoscope to take samples of tissue and bronchial washings or brushings for biopsy.

During a bronchoscopy, doctors can perform an ultrasound scan of the bronchial tubes, lymph nodes next to the trachea and lung tissue. This technique is called endobronchial ultrasound. It is used to identify abnormal structures and to help guide the collection of accurate biopsy samples.

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Doctors will do a biopsy of a neuroendocrine tumour or carcinoma to confirm the diagnosis. In a biopsy, tissues or cells are removed from the body so they can be examined in a laboratory. The pathologist will determine if a neuroendocrine tumour is present. If it is, the pathologist will also determine if it is benign or malignant, and which hormones it produces.

Often, a biopsy report cannot identify whether a neuroendocrine tumour is benign or malignant. For example, both benign and malignant tumours that develop from some types of neuroendocrine cells can look the same when examined under a microscope. Malignant or cancerous tumours are identified by their invasive behaviour or ability to spread to different sites in the body. The pathologist may use tumour markers to determine if a cancer is malignant. The most widely used tumour marker is Ki-67, a marker in dividing cells. If the Ki-67 stains many cells, it means that the cells in the sample are dividing and suggests a more aggressive tumour. Poorly differentiated neuroendocrine cancers are usually more aggressive.

The pathologist can also test the biopsy sample to identify the hormone produced by the tumour and to determine if it makes chromogranin. The results of these tests can also give doctors a baseline for tumour markers in blood, which may help them identify recurrence earlier.

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See a list of questions to ask your doctor about diagnostic tests.


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