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Myasthenia Gravis - The Resource
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THE THYMUS, THYMOMA AND THYMECTOMY The thymus gland lies in the upper part of the mediastinum behind the sternum and extends upwards into the root of the neck. It weighs about 10 to 15 g.(about half an ounce) at birth and begins to grow until the individual reaches puberty when it begins to atrophy. It’s maximum weight is around 30 - 40g (around 1 to 1.5 ounces) by the age of 40 it has returned to it’s weight at birth. The thymus consists of two lobes connected by areolar tissue. The lobes are enclosed in a fibrous capsule which dips into their substance dividing them into lobules that consist of an irregular branching framework of epithelial cells and lymphocytes. The Thymus is critically important in the body's response to disease invasion. White blood cells originate in the bone marrow. About half of them go directly into the bloodstream and tissue fluids, but the rest of them must pass through the Thymus gland. The Thymus gland is a central figure of the immune system because of its primary role in processing these white blood cells into T lymphocytes. These thymic lymphocytes carry out three defensive functions; First, they stimulate the production and growth of antibodies by other lymphocytes. Second, they stimulate the growth and action of the phagocytes, which surround and engulf invading viruses and microbes. Finally, the thymus lymphocytes recognize and destroy foreign and abnormal tissue. When the tissue being destroyed shouldn't be, it is considered an autoimmune disease for this reason. The origin of the name thymus is unclear. It may have been named because the gland resembles the herb thyme, or the name may have been derived from a Greek word meaning the soul or the heart, relating to the intimate anatomical relationship between the gland and the heart.
The answers supplied below are presented in general terms as background information only and should not be used to make specific decisions. Since each patient's situation is unique and the types of thymectomy being performed vary, it is essential to discuss in detail these and all other questions about the surgery with the MG specialist and the surgeon. What is a thymectomy & why is it performed? A thymectomy is the surgical removal of the thymus gland. The thymus has been demonstrated to play a role in the development of MG. It is removed in an effort to improve the weakness caused by MG, and to remove a thymoma if present. About 10% of MG patients have a tumor of the thymus called a thymoma. Most of these tumors are benign and tend to grow very slowly; on occasion they are malignant ("cancerous"). What is the function of the thymus? Is its removal harmful? The thymus plays a major role in the development of the body's immune system. This function appears virtually complete by birth. Removal of the thymus in the treatment of MG does not affect the immune system thereafter. Exactly where is the thymus located? The thymus is located in the front portion of the chest (anterior mediastinum) with "finger-like" extensions into the neck and consists of multiple lobes (two to five or more). In addition, varying amounts of thymic tissue may be present in the fat surrounding the lobes, both in the neck and chest. Who should have a thymectomy? Although it is not definitely established which patients should have a thymectomy or what type of operation should be performed, thymectomy is frequently recommended for patients under the age of 60 (occasionally older) with moderate to severe MG weakness. It is sometimes recommended for patients with relatively mild weakness, especially if there is weakness of the respiratory (breathing) or oropharyngeal (swallowing) muscles. It is also recommended for all patients with a thymoma. Thymectomy is usually not recommended for patients with weakness limited to the eye muscles, ocular myasthenia gravis. What should I expect as I consider a thymectomy? When a thymectomy is being considered, the patient is referred to a surgeon. It is important to choose a surgeon experienced in performing thymectomy for patients with MG. The surgeon will review the clinical records, examine the patient, discuss the surgical choices with the patient and make a recommendation. The surgeon also explains the anticipated pre- and post-operative course, possible complications, and the anticipated results. The patient, in consultation with the neurologist and surgeon, then makes a decision whether to proceed with thymectomy and the type of surgery to be used. What are the goals of thymectomy? The neurological goals of thymectomy are significant improvement in the patient's weakness, reduction in the medications being employed, and ideally eventually a permanent remission (complete elimination of all weakness off all medications). How is the surgery performed? There are three basic surgical approaches (see box), each with several variations. Regardless of the technique employed, the surgical goal is to remove the entire thymus. Many believe this should include removal of the adjacent fat; others are less sure. Trans-sternal Thymectomy Incision: Vertical (lengthwise) on the anterior chest; the sternum (breastbone) is "split" vertically. Thymus Removal: The chest and neck portion of the thymus are removed through this incision. Extended Form: The fat located in the front part of the chest next to the thymus, as well as the thymus, is removed. Complete removal of all tissue containing thymus is believed ensured. Combined Chest & Neck: A few MG Centers add a formal neck dissection to the sternal technique to also ensure the removal of all the thymus in the neck. Thymoma: Most recommend the transsternal approach for removal of a thymoma. Trans-cervical Thymectomy Incision: Transverse (horizontal) across the lower neck. Thymus Removal: The chest portion of the thymus is removed through this incision. Extended Form: The "extended" form allows improved exposure of the thymus in the chest with more complete removal of the thymus. Although the adjacent fat is also removed, less is removed than in the extended trans-sternal thymectomy. Videoscopic (VATS) Thymectomy Incision: Several small incisions on the right or left side of the chest. Thymus Removal: Fiber-optic instruments are used. These are small flexible tubes with a light at the end through which small instruments can be passed. The amount of thymus and fat removed is variable. Extended Form: In the "VATET" form, incisions are made on both sides of the chest, as well as in the neck, for "more complete" removal of the thymus. Of Note: The videoscopic procedures are relatively new and are in a relatively early investigative stage. There is a relatively new procedure that allows for minimal invasion and without having to crack open the sternum. More information on the Da Vinci Surgical System What are the results of thymectomy? Many neurologist experienced in the treatment of MG are convinced that thymectomy plays an important role in the therapy of MG, although the benefit is variable, hard to define, and remains unproven by today's strict standards. In general, most patients begin to improve within one year following thymectomy and a variable number eventually develop a permanent remission (no weakness and no medication). Some physicians believe the remission rates after surgery are in the 20-40% range regardless of the type of thymectomy performed. Others believe that the remission rates following the more extensive procedures are in the 40-60% range 5 or more years after the surgery. It is important to note that rigorous scientific studies are needed to resolve the debate concerning the role of and best method of performing thymectomy in the treatment of MG patients. What type of thymectomy should I have? Since there is no universal agreement, or unequivocal proof, as to which type of thymectomy is best, it is difficult for patients to decide what is best for them. There is, however, general agreement that the entire thymus should be removed and that the patient should select the procedure that ensures as much as possible that this is accomplished. Some surgeons believe that all the surrounding fat should be removed as well, because it frequently contains microscopic (very small) amounts of thymus; others believe this may not be necessary. The most frequently used procedure is the extended form of the transsternal thymectomy. Its proponents believe that it gives the best assurance that in most instances the entire thymus is being removed and performed safely, and that it produces the best long-term results. These operations are now performed with minimal risk. Those advocating the transcervical or the videoscopic thymectomy do not share the above observations. They believe the "minimally invasive" procedures (transcervical and videoscopic) are as effective. Since there is no absolute proof as to which type of thymectomy is the procedure of choice, patients need to be fully informed, to review the evidence presented by the neurologist and surgeon caring for them, and perhaps obtain additional consultation. What can the MG patient expect in the pre-operative, anesthesia and post-operative periods? In general, MG Centers have developed protocols for the care of MG patients and have a team of neurologists, surgeons, pulmonologists, intensive care and respiratory care specialists, nurses, and anesthesiologists caring for MG patients undergoing a thymectomy. Patients should discuss all aspects of the pre-and post-operative care and anesthesia with the surgeon, anesthesiologist, and neurologist. To reduce the risks of post-operative respiratory complications or the post-operative need for prolonged respiratory support with a ventilator (breathing machine), many patients require pre-operative plasma exchange or intravenous immunoglobulin (IVIg), and some require immunosuppressive therapy as well. Pyridostigmine, if being administered, may or may not be discontinued the day of surgery, and may or may not be restarted immediately post-operatively. The anesthesia for patients with MG is similar to the anesthesia given to other patients. An endotracheal tube (tube in the windpipe) is inserted after the patient is asleep. Muscle relaxing drugs, however, are usually avoided. The patient may or may not be extubated (removal of the endotracheal tube) upon awakening, depending on the patient's strength. If the endotracheal tube is not removed on awakening, the tube will be attached to a ventilator. Ordinarily after the surgery, the patient will go to a Recovery Room, Respiratory Care Unit, or Intensive Care Unit depending on each hospital's method of taking care of MG patients following surgery. A ventilator may be required depending on the type of operation and the severity of the patient's weakness. As soon as the breathing tube has been removed, the patient will be asked and helped to deep breathe and cough frequently to keep the lungs clear of secretions. One or two chest tubes (small tubes exiting the chest and attached to drainage bottles) are usually used after the transsternal and videoscopic operations, and removed soon after surgery. Pain is minimal following transcervical thymectomy; it is usually mild following videoscopic thymectomy although some patients have reported late pain. The pain associated with transsternal thymectomy is temporary, is now well controlled with medication, gradually resolves within 3-5 days, and patients typically will require minimal pain medication on hospital discharge. The length of time in the hospital will vary depending on the type of surgery and the patient's overall weakness. In most cases the patient will be ready to go home in a few days to a week. The patient's preoperative medications, immunosuppression, and other forms of therapy, are usually resumed after surgery for variable periods of time depending on the MG symptoms and the neurologist's recommendations. When can I return to my usual activities? Patients should discuss this with the surgeon in advance and let their employer or school know the anticipated time they will miss. The recovery period and the time away from regular activities, like work or school, will vary depending on the patient's weakness, type of surgery, and the type of the patient activities. A patient who does heavy lifting or construction work will be off work longer than someone who has a desk type job. In general, 3 to 6 weeks of limited activities is a common length of time for recovery.
In the normal thymus, bone marrow–derived precursor cells destined to become thymocytes (or T lymphocytes) enter the thymus at the corticomedullary junction and change as they pass through the thymus. These cells can be characterized in their developmental progression by changes in 3 markers: CD4, CD8, and the T-cell receptor (TCR)–CD3 complex. As many as 50% of patients with thymoma have MG, and approximately 15% of patients with MG have thymoma (Temes, 1999). MG is caused by autoantibodies to postsynaptic nicotinic acetylcholine receptors (anti-AChRs) at the neuromuscular junction, causing weakness of skeletal muscles. Some patients with thymoma-associated MG have an inflammatory myopathy of striated and cardiac muscles. Cardiac myositis may cause heart failure, cardiac arrhythmia, and sudden death (Mygland, 2000; Agarwala, 1996). Neuromyotonia also can be associated with thymoma. Patients with neuromyotonia have hyperactivity of peripheral motor nerves, which causes muscle cramps, muscle twitching, and, sometimes, muscle hypertrophy. Muscle biopsy samples demonstrate patchy inflammatory infiltrates. Antibodies against a presynaptic structure, the voltage-gated potassium channels of peripheral nerves, have been detected in patients with neuromyotonia with or without thymoma. These channels regulate nerve excitability. Neuromyotonia and antibodies to the voltage-gated potassium channels also have been found in patients with MG. Of patients with MG and neuromyotonia, 20% have been demonstrated to have thymoma (Hart, 2000; Agarwala, 1996; Fauci, 1998). In addition to these autoantibodies, patients with thymoma-associated MG produce autoantibodies to a variety of neuromuscular antigens, including antibodies to the skeletal muscle calcium release channel (ryanodine receptor of sarcoplasmic reticulum) and antibodies to cytoplasmic filamentous proteins, particularly titin, or neurofilaments. Myoid (musclelike) thymic epithelial cells express epitopes shared by the target antigens for some of these antibodies. Autoreactive T lymphocytes are assumed to generate in the thymic tumor and, subsequently, stimulate antibody production against various muscle antigens. MG with myositis tends to be severe, with poor response to resection of the thymoma (Mygland, 2000; Agarwala, 1996; Fauci, 1998). WHAT? OK, let's try this definition: The thymus is located in the upper chest just below the neck. It is a small organ that produces certain types of white blood cells before birth and during childhood. These white blood cells are called lymphocytes and are an important part of the body's immune system. Once released from the thymus, lymphocytes travel to lymph nodes where they help to fight infections. The thymus gland becomes smaller in adulthood and is gradually taken over by fat tissue. Although rare, thymomas are the most common type of thymic cancer. They arise from thymic epithelial cells, which make up the covering of the thymus. Thymomas frequently contain lymphocytes, which are noncancerous. Thymomas are classified as either noninvasive (previously called "benign") or invasive (previously called "malignant"). Noninvasive thymomas are those in which the tumor is encapsulated and easy to remove. Invasive thymomas have spread to nearby structures (such as the lungs) and are difficult to remove. Approximately 30% to 40% of thymomas are of the invasive type. Thymoma affects men and women equally. It is usually diagnosed between the ages of 40 and 60 years. Thymomas are uncommon in children. Stages of malignant thymomaOnce malignant thymoma is found, more tests will be done to find out if cancer cells have spread to other parts of the body. This is called staging. A doctor needs to know the stage of the disease to plan treatment. The following staging system may be used for malignant thymoma:
Stage I malignant thymoma may be referred to as noninvasive malignant thymoma. Stages II through IVb malignant thymoma may be referred to as invasive malignant thymoma. Stages of malignant thymomaOnce malignant thymoma is found, more tests will be done to find out if cancer cells have spread to other parts of the body. This is called staging. A doctor needs to know the stage of the disease to plan treatment. The following staging system may be used for malignant thymoma:
Stage I malignant thymoma may be referred to as noninvasive malignant thymoma. Stages II through IVb malignant thymoma may be referred to as invasive malignant thymoma. For more information, U.S. residents may call the National Cancer Institute's (NCI's) Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237) Monday through Friday from 9:00 a.m. to 4:30 p.m. Deaf and hard-of-hearing callers with TTY equipment may call 1-800-332-8615. The call is free and a trained Cancer Information Specialist is available to answer your questions. Web sites and Organizations The NCI's Cancer.gov Web site (http://cancer.gov) provides online access to information on cancer, clinical trials, and other Web sites and organizations that offer support and resources for cancer patients and their families. There are also many other places where people can get materials and information about cancer treatment and services. Local hospitals may have information on local and regional agencies that offer information about finances, getting to and from treatment, receiving care at home, and dealing with problems associated with cancer treatment. Publications The NCI has booklets and other materials for patients, health professionals, and the public. These publications discuss types of cancer, methods of cancer treatment, coping with cancer, and clinical trials. Some publications provide information on tests for cancer, cancer causes and prevention, cancer statistics, and NCI research activities. NCI materials on these and other topics may be ordered online or printed directly from the NCI Publications Locator (https://cissecure.nci.nih.gov/ncipubs). These materials can also be ordered by telephone from the Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237), TTY at 1-800-332-8615. LiveHelp The NCI's LiveHelp service, a program available on several of the Institute's Web sites, provides Internet users with the ability to chat online with an Information Specialist. The service is available from 9:00 a.m. to 10:00 p.m. Eastern time, Monday through Friday. Information Specialists can help Internet users find information on NCI Web sites and answer questions about cancer. |
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