Neuroblastoma

Cancer starts forming in the body when certain cells start to grow out of control at an alarmingly fast rate. Neuroblastoma is aggressive cancer that affects the nervous system which contains the brain, spinal cord and the nerves that go all over the body. It is most commonly found in the adrenal glands that are sitting on top of the kidneys. Neuroblastoma can affect children under the age of ten but is most prevalent in children ages one through five. Neuroblastoma starts developing in the early nerve cells in the embryo1. Neuroblastoma targets the autonomic nervous system which goes all over the body. For the parents of the children, who are diagnosed with neuroblastoma or on the verge of being diagnosed it is important to know the anatomy of the nervous system and kidneys, how to diagnose it, the staging of neuroblastoma and all the treatments that are involved.

The anatomy of the nervous system and the kidneys are very complex. The nervous system is a large organization of nerves and glands throughout the body. There are two main parts to the nervous system, the central nervous system, and the peripheral nervous system2. The central nervous system consists of two parts, the spinal cord, and the brain. The brain is the main control unit that sends out commands for the rest of the body, and the spinal cord is the path that these commands take. The brain and spinal cord are made up of billions of neurons. Neurons are specialized cells that connect with each other and make sure that the brain’s message reaches its destination2.

The peripheral nervous system has two main parts and two subcategories. The two parts of the peripheral nervous system are the nerves and the ganglia outside of the brain. The two subcategories of the peripheral nervous system are the somatic nervous system and the autonomic nervous system. The somatic nervous system is what controls the voluntary actions such as walking or eating. The autonomic nervous system is what controls the involuntary actions such as breathing and the heartbeat. The peripheral nervous system is what connects the central nervous system to the limbs and organs of the body. When the brain sends a message, it travels down the spinal cord to the appropriate nerve, then down the nerve to the appropriate body part passing through a few ganglia on the way.

The kidneys are a bean-shaped organ that functions as the garbage disposal of the body, approximately one-third of the blood leaving the heart passes through the kidneys before going to the rest of the body. The kidneys are located against the posterior muscular wall of a human’s abdominal cavity. The kidneys are not directly mirrored, the left kidney is slightly superior to the right kidney. The main parts of the kidney include the renal capsule, the renal cortex, the renal medulla, the renal pelvis, and around a million nephrons3.

The renal capsule is the fibrous connective tissue that makes up the outermost shell of the kidneys. The renal capsule is primarily responsible for providing protection and maintaining the shape of the kidneys. The renal cortex is made up of granular tissue. The main purpose of the renal cortex is to separate the renal capsule from the renal medulla3. The renal cortex also provides an area for the glomerular capillaries and the arterioles and venules. The renal medulla is located just inside of the renal cortex. The renal medulla is the area where most of the filtration happens. Inside the renal medulla are several pyramidal shaped masses of tissue called renal pyramids. Inside each renal pyramid is a dense network of nephrons that work together to filter the blood and excrete the waste from your body. The nephrons are what separate and filter the blood and water3. At the end of each nephron is a cup-shaped structure called the Bowman's capsule. The Bowman's capsule surrounds a tuft of capillaries called glomeruli. The glomeruli are what carry blood to and from the kidneys. Every part of the nephron is permeable to different molecules making it a very efficient filter. The renal pelvis is what connects the kidney to the rest of the body3. It is also what contains the hilum, or the concave part of the kidney. The hilum is where the blood vessels and nerves enter and leave the kidney. Renal arteries are what supply the kidneys with blood and come from the abdominal aorta.

On top of each kidney sits an adrenal gland which is vital to a person’s wellbeing. Adrenal glands regulate the hormones that we need in times of extreme stress. Each adrenal gland is only two and a half inches long and one-inch wide4. The adrenal gland has three parts which are: the capsule, the cortex, and the medulla. The capsule is the outermost layer which is composed of fat. The main purpose of this layer is to provide protection for the innermost parts. The cortex or second layer is eighty percent of the adrenal gland4. The cortex completely surrounds the innermost part of the medulla. The cortex has three zones; the zona glomerulosa, the zona fasciculata and the zona reticularis. These regulate the fluid and mineral excretion. The medulla is largely responsible for how a human’s body regulates stress. There are three different catecholamines secreted by the medulla: epinephrine, norepinephrine, and dopamine. These three hormones are called neurotransmitters. When a body undergoes stress, the brain sends a signal down the spinal cord to the adrenal medulla to start secreting neurotransmitters, this is a human’s stress mechanism3.

Neuroblastoma causes certain problems to appear in many aspects of your body. Symptoms include abdominal pain, changes in bowel patterns, feeling a lump underneath the skin that isn’t painful to the touch, chest pain, wheezing, bone pain, back pain and weight loss5. If a person has any of these symptoms, they should see a physician immediately. If the physician suspects there is something wrong they will order further testing.

Radiological imaging plays a very large role in noticing and diagnosing a neuroblastoma tumor. Normally the first step is a physical exam5. From there a blood or urine sample is often taken to examine the levels of hormones. After that images are taken to see if there is a neuroblastoma present through ultrasound, x-ray, computed tomography, magnetic resonance imaging and positron emission tomography5. Ultrasound is the first step in small children because it is quick, easy, and there is no radiation involved. Ultrasound bounces sound waves to create pictures of the inside of the body. A small wand or transducer is placed on the skin with gel on the top. The transducer produces sound waves and then picks up the echoes as they bounce off various parts of the body. This creates a black and white image on a computer screen. Ultrasound is the first step in small children because it is quick, easy, and there is no radiation involved. The x-ray might be used if the child is having symptoms, but it is unclear what is causing them. However, the images might not be clear enough or have enough detail to be of much use. If the child has already been diagnosed with Neuroblastoma, x-rays can be useful to see if cancer has spread to the bones. A chest x-ray could be ordered if the doctor thinks that it could have spread to the lungs. Computer Tomography, known as CT, is a test that creates detailed cross-sectional images of the body. It takes multiple pictures and rotates around the body, giving the doctor a very thorough image of the soft tissues in the body. Computed tomography is often used to search for Neuroblastomas in the chest abdomen and pelvic regions. Magnetic Resonance Imaging, known as MRI, uses strong magnets and radio waves to create the images so there is no radiation. Magnetic resonance imaging provides a more detailed image of the soft tissue like the brain and spinal cord, which makes it better for looking at neuroblastomas. However, because of the degree of stillness, the length of the test and the loud noises it is harder to use on young children. Positron Emission Tomography is where a small amount of radioactive sugar is injected into the blood. An hour after the injection the patient is laid on the table where a special camera is used to create pictures of the whole body. Because cancer cells are fast growing they absorb a large amount of the radioactive sugar. If the imaging results show a mass that could be a tumor, a tissue biopsy is ordered to figure out what the mass is.

During a biopsy, the doctor removes a portion of the mass. There are two different types of biopsies: incision biopsy and needle biopsy. An incision biopsy is where you remove a portion of the mass through a cut in the skin. A needle biopsy is where you remove a portion of the mass through a needle. During a needle biopsy, computed tomography or ultrasound can be used to help guide the needle to the exact area of the mass. After obtaining the samples, the sample is then sent off to the lab to be viewed under a microscope.

There are various treatment plans for neuroblastoma depending upon the stage and where the tumor is located. In young children under six months, with a small tumor on the adrenal gland observation alone is the normal treatment plan. This allows the doctor the opportunity to study the tumor and see if it will just go away on its own. If the patient is older than six months and the tumor is in an opportune place, surgery would be considered. In most cases, a surgery can remove the entire tumor and bring remission. If the tumor is located to close to internal organs or other vital structures, the entire tumor might not be able to be removed. During the surgery, the surgeon also removes small lymph nodes that are nearby the adrenal glands to examine them for cancer cells. If the tumor is inoperable, or part of it is unable to be removed, chemotherapy is used to attack the remaining cancer cells.

Chemotherapy is a type of treatment that uses certain cancer-killing drugs to create a standardized chemotherapy regiment6. The drugs used to attack and kill fast-dividing cells. There are several cells in a human’s body that divide rapidly naturally, like hair and bone marrow. Chemotherapy also attacks these cells as well causing hair follicles to die, and white blood cells to die. There are a variety of drugs that are used to attack a neuroblastoma that includes; Cyclophosphamide, Cisplatin, Vincristine, Doxorubicin, Etoposide, and Topotecan6. These drugs are used intravenously or into a vein through a needle. The doctor determines the dosages by what stage and risk group the patient is in.

Neuroblastoma goes through a progression of certain stages. The staging includes Stage I, Stage IIA, Stage IIB, Stage III, Stage IV, and Stage IVS5. Stage I is when the neuroblastoma is in one area and can be completely removed through surgery5. Stage IIA is when the neuroblastoma is not easily removed through surgery, so you can go through other treatments to help combat the disease5. The lymph nodes at this stage are not affected by the cancer cells. Stage IIB is the stage where neuroblastoma is also considered not to be easily removed by surgery. But at this stage, the lymph nodes connected are affected by cancer cells5. Stage III is when the neuroblastoma is considered advanced. This means that the tumor is larger in size and not removable through surgery5. Stage IV is the stage where the neuroblastoma has spread to other parts of the body5. Stage IVS is a special category of neuroblastoma that doesn’t act like the other forms and it's not clear why. This stage only applies to children younger than one year of age5. This stage also indicates that the cancer cells have spread to other parts of the body5.

If the patient is in a high-risk group, the doctor would order larger doses given more frequently to attack cancer vigorously. The treatment is given in rounds which include three or four days of treatment, followed by a few weeks to allow the body to recover. During the recovery time, more images are taken to keep track of cancer. For the children in the low-risk group, the five-year survival rate is 95%7. For children in the high-risk group, the five-year survival rate is between 40%-50%7.

Even though neuroblastoma is an aggressive cancer that is primarily found in the adrenal glands in children, the chances of survival are very high if it is found and treated quickly. Neuroblastoma is normally found in the adrenal glands which are found on top of the kidneys, and are responsible for the secretion of hormones that humans require in times of stress. Neuroblastoma affects the nervous system which consists of the brain, spinal cord, and nerves, but more specifically it attacks the autonomic nervous system. Neuroblastoma can also start developing in the early nerve cells in the embryo. For the parents of the children, who are diagnosed with neuroblastoma or on the verge of being diagnosed, it is important that they know the anatomy of the nervous system and kidneys, how to diagnose it, the staging of neuroblastoma and all the treatments that are involved.