Los avances de la medicina en el campo de la genética, por ende de la herencia, están modificando el paisaje del conocimiento médico de las enfermedades. Este BLOG intenta informar acerca de los avances proveyendo orientación al enfermo y su familia así como información científica al profesional del equipo de salud de habla hispana.
viernes, 19 de abril de 2019
Childhood Vascular Tumors Treatment (PDQ®)—Patient Version - National Cancer Institute
Because malignant vascular tumors are rare in children, there is not a lot of information about what treatment works best.
Tests are used to detect (find) and diagnose childhood vascular tumors.
The following tests and procedures may be used:
Physical exam and history: An exam of the body to check general signs of health, including checking for signs of disease, such as lumps, lesions, or anything else that seems unusual. A history of the patient’s health habits and past illnesses and treatments will also be taken.
Ultrasound exam: A procedure in which high-energy sound waves (ultrasound) are bounced off internal tissues or organs and make echoes. The echoes form a picture of body tissues called a sonogram. The picture can be printed to be looked at later.ENLARGEAbdominal ultrasound. An ultrasound transducer connected to a computer is pressed against the skin of the abdomen. The transducer bounces sound waves off internal organs and tissues to make echoes that form a sonogram (computer picture).
CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.ENLARGEComputed tomography (CT) scan of the abdomen. The child lies on a table that slides through the CT scanner, which takes x-ray pictures of the inside of the abdomen.
MRI (magnetic resonance imaging): A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body. This procedure is also called nuclear magnetic resonance imaging (NMRI).ENLARGEMagnetic resonance imaging (MRI) of the abdomen. The child lies on a table that slides into the MRI scanner, which takes pictures of the inside of the body. The pad on the child’s abdomen helps make the pictures clearer.
Biopsy: The removal of cells or tissues so they can be viewed under a microscope by a pathologist to check for signs of cancer. A biopsy is not always needed to diagnose a vascular tumor.
Childhood vascular tumors may be classified into four groups.
Benign tumors
Benign tumors are not cancer. This summary has information about the following benign vascular tumors:
Intermediate tumors that are locally aggressive often spread to the area around the tumor. This summary has information about the following locally aggressive vascular tumors:
Intermediate (rarely metastasizing) tumors sometimes spread to other parts of the body. This summary has information about the following vascular tumors that rarely metastasize:
There are different types of treatment for childhood vascular tumors.
Children with childhood vascular tumors should have their treatment planned by a team of health care providers who are experts in treating cancer in children.
Treatment for childhood vascular tumors may cause side effects.
Eleven types of standard treatment are used:
Beta-blocker therapy
Surgery
Photocoagulation
Embolization
Chemotherapy
Sclerotherapy
Radiation therapy
Targeted therapy
Immunotherapy
Other drug therapy
Observation
New types of treatment are being tested in clinical trials.
Patients may want to think about taking part in a clinical trial.
Patients can enter clinical trials before, during, or after starting their cancer treatment.
Follow-up tests may be needed.
There are different types of treatment for childhood vascular tumors.
Different types of treatment are available for children with vascular tumors. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment.
Because vascular tumors in children are rare, taking part in a clinical trial should be considered. Some clinical trials are open only to patients who have not started treatment.
Children with childhood vascular tumors should have their treatment planned by a team of health care providers who are experts in treating cancer in children.
Treatment will be overseen by a pediatric oncologist, a doctor who specializes in treating children with cancer. The pediatric oncologist works with other pediatrichealth care providers who are experts in treating children with cancer and who specialize in certain areas of medicine. These may include the following specialists:
Pediatric vascular anomaly specialist (expert in treating children with vascular tumors).
Treatment for childhood vascular tumors may cause side effects.
For information about side effects that begin during treatment for cancer, see our Side Effects page.
Some treatments, such as chemotherapy and radiation therapy, cause side effects that continue or appear months or years after treatment has ended. These are called late effects. Late effects of treatment may include the following:
Physical problems.
Changes in mood, feelings, thinking, learning, or memory.
Some late effects may be treated or controlled. It is important to talk with your child's doctors about the possible late effects caused by some treatments. (See the PDQ summary on Late Effects of Treatment for Childhood Cancer for more information).
Eleven types of standard treatment are used:
Beta-blocker therapy
Beta-blockers are drugs that decrease blood pressure and heart rate. When used in patients with vascular tumors, beta-blockers may help shrink the tumors. Beta-blocker therapy may be given by vein (IV), by mouth, or placed on the skin (topical). The way the beta-blocker therapy is given depends on the type of vascular tumor and where the tumor first formed.
The following types of surgery may be used to remove many types of vascular tumors:
Excision: Surgery to remove the entire tumor and some of the healthy tissue around it.
Laser surgery: A surgical procedure that uses a laser beam (a narrow beam of intense light) as a knife to make bloodless cuts in tissue or to remove a skin lesion such as a tumor. Surgery with a pulsed dye laser may be used for some hemangiomas. This type of laser uses a beam of light that targets blood vessels in the skin. The light is changed into heat and the blood vessels are destroyed without damaging nearby skin.
Curettage: A procedure in which abnormal tissue is removed using a small, spoon-shaped instrument called a curette.
Total hepatectomy and liver transplant: A surgical procedure to remove the entire liver followed by a transplant of a healthy liver from a donor.
The type of surgery used depends on the type of vascular tumor and where the tumor formed in the body.
For malignant tumors, after the doctor removes all the cancer that can be seen at the time of the surgery, some patients may be given chemotherapy or radiation therapy after surgery to kill any cancer cells that are left. Treatment given after the surgery, to lower the risk that the cancer will come back, is called adjuvant therapy.
Photocoagulation
Photocoagulation is the use of an intense beam of light, such as a laser, to seal off blood vessels or destroy tissue. It is used to treat pyogenic granuloma.
Embolization
Embolization is a procedure that uses particles, such as tiny gelatin sponges or beads, to block blood vessels in the liver. It may be used to treat some benign vascular tumors of the liver and kaposiform hemangioendothelioma.
Chemotherapy
Chemotherapy is a treatment that uses drugs to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. There are different ways to give chemotherapy:
Systemic chemotherapy: When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach tumor cells throughout the body. Sometimes more than one anticancer drug is given. This is called combination chemotherapy.
Topical chemotherapy: When chemotherapy is applied to the skin in a cream or lotion, the drugs mainly affect tumor cells in the treated area.
The way the chemotherapy is given depends on the type of the vascular tumor being treated. Systemic and topical chemotherapy are used to treat some vascular tumors.
Sclerotherapy
Sclerotherapy is a treatment used to destroy the blood vessel that leads to the tumor and the tumor. A liquid is injected into the blood vessel, causing it to scar and break down. Over time, the destroyed blood vessel is absorbed into normal tissue. The blood flows through nearby healthy veins instead. Sclerotherapy is used in the treatment of epithelioid hemangioma.
Radiation therapy
Radiation therapy is a treatment that uses high-energy x-rays or other types of radiation to kill tumor cells or keep them from growing. There are two types of radiation therapy:
The way the radiation therapy is given depends on the type of the vascular tumor being treated. External radiation is used to treat some vascular tumors.
Targeted therapy
Targeted therapy is a type of treatment that uses drugs or other substances to attack specific tumor cells. Targeted therapies usually cause less harm to normal cells than chemotherapy or radiation therapy do. Different types of targeted therapy are being used or studied to treat childhood vascular tumors:
Angiogenesis inhibitors: Angiogenesis inhibitors are drugs that stop cells from dividing and prevent the growth of new blood vessels that tumors need to grow. The targeted therapy drugs thalidomide, sorafenib, pazopanib, and sirolimus are angiogenesis inhibitors used to treat childhood vascular tumors.
Immunotherapy is a treatment that uses the patient’s immune system to fight disease. Substances made by the body or made in a laboratory are used to boost, direct, or restore the body’s natural defenses against disease.
Interferon is a type of immunotherapy used to treat childhood vascular tumors. It interferes with the division of tumor cells and can slow tumor growth. It is used in the treatment of juvenile nasopharyngeal angiofibroma, kaposiform hemangioendothelioma, and epithelioid hemangioendothelioma.
Other drug therapy
Other drugs used to treat childhood vascular tumors or manage their effects include the following:
Non-steroidal anti-inflammatory drugs (NSAIDs): NSAIDs are commonly used to decrease fever, swelling, pain, and redness. Examples of NSAIDs are aspirin, ibuprofen, and naproxen. In the treatment of vascular tumors, NSAIDs can increase the flow of blood through the tumors and decrease the chance that an unwanted blood clot will form.
Antifibrinolytic therapy: These drugs help the blood clot in patients who have Kasabach-Merritt syndrome. Fibrin is the main protein in a blood clot that helps stop bleeding and heal wounds. Some vascular tumors cause fibrin to break down and the patient's blood does not clot normally, causing uncontrolled bleeding. Antifibrinolytics help prevent the breakdown of fibrin.
New types of treatment are being tested in clinical trials.
Information about clinical trials is available from the NCI website.
Patients may want to think about taking part in a clinical trial.
For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the research process. Clinical trials are done to find out if new treatments are safe and effective or better than the standard treatment.
Many of today's standard treatments are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.
Patients who take part in clinical trials also help improve the way disease will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.
Patients can enter clinical trials before, during, or after starting their cancer treatment.
Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose tumors have not gotten better. There are also clinical trials that test new ways to stop tumors from recurring (coming back) or reduce the side effects of treatment.
Clinical trials are taking place in many parts of the country. Information about clinical trials supported by NCI can be found on NCI’s clinical trials search webpage. Clinical trials supported by other organizations can be found on the ClinicalTrials.gov website.
Follow-up tests may be needed.
Some of the tests that were done to diagnose the vascular tumor may be repeated. Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests.
Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your child's condition has changed or if the tumor has recurred (come back). These tests are sometimes called follow-up tests or check-ups.
These tumors are not usually seen at birth but appear when the infant is 3 to 6 weeks old. Most hemangiomas get bigger for about 5 months and then stop growing. The hemangiomas slowly fade away over the next several years, but a red mark or loose or wrinkled skin may remain. It is rare for an infantile hemangioma to come back.
Infantile hemangiomas may be on the skin, in the tissue below the skin, and/or in an organ. They are usually on the head and neck but can be anywhere on or in the body. Hemangiomas may appear as a single lesion, one or more lesions spread over a larger area of the body, or multiple lesions in more than one part of the body. Lesions that are spread over a larger area of the body or multiple lesions are more likely to cause problems.
Infantile hemangioma with minimal or arrested growth (IH-MAG) is a certain type of infantile hemangioma that is seen at birth and does not tend to get bigger. The lesion appears as light and dark areas of redness in the skin. Hemangiomas of this type go away over time without treatment.
Risk Factors
Anything that increases your risk of getting a disease is called a risk factor. Having a risk factor does not mean that you will get the disease; not having risk factors doesn’t mean that you will not get the disease. Talk with your child's doctor if you think your child may be at risk.
Infantile hemangiomas are more common in the following:
Girls.
Whites.
Premature babies.
Twins, triplets, or other multiple births.
Babies of mothers who are older at time of the pregnancy or who have problems with the placenta during pregnancy.
Other risk factors for infantile hemangiomas include the following:
Having a family history of infantile hemangioma, usually in a mother, father, sister, or brother.
PHACE syndrome: A syndrome in which the hemangioma spreads across a large area of the body (usually the head or face). Other health problems that affect the large blood vessels, heart, eyes, and/or brain may also occur.
Having more than one hemangioma or an airway or ophthalmic hemangioma increases the risk of having other health problems.
Multiple hemangiomas: Having more than five hemangiomas on the skin is a sign that there may be hemangiomas in an organ. The liver is affected most often. Heart, muscle, and thyroid gland problems can also occur.
Airway hemangiomas: Hemangiomas in the airway usually occur along with a large, beard-shaped area of hemangioma on the face (from the ears, around the mouth, lower chin, and front of neck). It is important that airway hemangiomas are treated before the child has trouble breathing.
Ophthalmic hemangiomas: Hemangiomas that involve the eye may cause vision problems or blindness. Infantile hemangiomas can occur in the conjunctiva (a membrane that lines the inner surface of the eyelid and covers the front part of the eye). These hemangiomas may be linked with other abnormalconditions of the eye. It is important that children with an ophthalmic hemangioma are examined by an ophthalmologist.
Signs and Symptoms
Infantile hemangiomas may cause any of the following signs and symptoms. Check with your child’s doctor if your child has any of the following:
Skin lesions: An area of spidery veins or lightened or discolored skin may appear before the hemangioma does. Hemangiomas occur as firm, warm, bright red to crimson lesions on the skin or may look like a bruise. Lesions that form ulcers are also painful. Later, as the hemangiomas go away, they begin fading in the center before flattening and losing color.
Lesions below the skin: Lesions that grow under the skin in the fat may appear blue or purple. If the lesions are deep enough under the skin surface, they may not be seen.
Lesions in an organ: There may be no signs that hemangiomas have formed on an organ.
Although most infantile hemangiomas are nothing to worry about, if your child develops any lumps or red or blue marks on the skin check with your child's doctor. He or she can refer the child to a specialist if needed.
Diagnostic Tests
A physical exam and history are usually all that are needed to diagnose infantile hemangiomas. If there is something about the tumor that looks unusual, a biopsy may be done. If the hemangioma is deeper inside the body with no change to the skin, or the lesions are spread across a large area of the body, an ultrasound may be done. See the General Information section for a description of these tests and procedures.
If the hemangiomas are part of a syndrome, more tests may be done, such as an echocardiogram, MRI, magnetic resonance angiogram, and eye exam.
Treatment
Most hemangiomas fade and shrink without treatment. If the hemangioma is large or causing other health problems, treatment may include the following:
Steroid therapy, before beta-blocker therapy is begun or when beta-blockers cannot be used.
Pulsed dye laser surgery, for hemangiomas that have ulcers or have not completely gone away.
Surgery (excision) for hemangiomas that have ulcers, cause vision problems, or have not completely gone away. Surgery may also be used for lesions on the face that do not respond to other treatment.
Topical beta-blocker therapy for hemangiomas that are in one area of the skin.
Combined therapy, such as propranolol and steroid therapy or propranolol and topical beta-blocker therapy.
A clinical trial of beta-blocker therapy (nadolol and propranolol).
A clinical trial of topical beta-blocker therapy (timolol).
Congenital Hemangioma
Congenital hemangioma is a benign vascular tumor that begins forming before birth and is fully formed when the baby is born. They're usually on the skin but can be in another organ. A congenital hemangioma may occur as a rash of purple spots and the skin around the spot may be lighter.
There are three types of congenital hemangiomas:
Rapidly Involuting Congenital Hemangioma: These tumors go away on their own 12 to 15 months after birth. They can form ulcers, bleed, and cause temporary heart and blood clotting problems. The skin may look a little different even after the hemangiomas go away.
Partial Involuting Congenital Hemangioma: These tumors do not go away completely.
Non-Involuting Congenital Hemangioma: These tumors never go away on their own.
Treatment of non-involuting congenital hemangioma may include the following:
Surgery to remove the tumor, depending on where it is and whether it is causing symptoms.
Benign Vascular Tumors of the Liver
Benign vascular tumors of the liver may be focal vascular lesions (a single lesion in one area of the liver), multiple liver lesions (multiple lesions in one area of the liver), or diffuseliver lesions (multiple lesions in more than one area of the liver).
The liver has many functions, including filtering blood and making proteins needed for blood clotting. Sometimes, blood that normally flows through the liver is blocked or slowed by the tumor. This sends blood directly to the heart without going through the liver and is called a liver shunt. This can cause heart failure and problems with blood clotting.
Focal Vascular Lesions
Focal vascular lesions are usually rapidly involuting congenital hemangiomas or non-involuting congenital hemangiomas.
Surgery, for lesions that do not respond to other treatment.
Multiple and Diffuse Liver Lesions
Multifocal and diffuse lesions of the liver are usually infantile hemangiomas. Diffuse lesions of the liver can cause serious effects, including problems with the thyroid gland and heart. The liver can enlarge, press on other organs, and cause more symptoms.
Diagnostic Tests
See the General Information section for a description of tests and procedures used to diagnose multifocal or diffuse benign vascular lesions.
Treatment
Treatment of multifocal liver lesions may include the following:
Observation for lesions that do not cause symptoms.
Total hepatectomy and liver transplant, when the lesions do not respond to drug therapy. This is done only when the lesions have spread widely in the liver and more than one organ has failed.
If a vascular lesion of the liver does not respond to standard treatments, a biopsy may be done to see if the tumor has become malignant.
Anything that increases your risk of getting a disease is called a risk factor. Having a risk factor does not mean that you will get the disease; not having risk factors doesn’t mean that you will not get the disease. Talk with your child's doctor if you think your child may be at risk. Spindle cell hemangiomas are likely to occur in children with the following syndromes:
Spindle cell hemangiomas appear on or under the skin. They are painful red-brown or bluish lesions that usually appear on the arms or legs. They can begin as one lesion and develop into more lesions over years.
Spindle cell hemangiomas may come back after surgery.
Epithelioid Hemangioma
Epithelioid hemangiomas usually form on or in the skin, especially the head, but can occur in other areas, such as bone.
Signs and Symptoms
Epithelioid hemangiomas are sometimes caused by injury. On the skin, they may appear as firm pink to red bumps and may be itchy. Epithelioid hemangioma of the bone may cause swelling, pain, and weakened bone in the affected area.
Epithelioid hemangiomas often come back after treatment.
Pyogenic Granuloma
Pyogenic granuloma is also called lobular capillary hemangioma. It is most common in older children and young adults but may occur at any age.
The lesions are sometimes caused by injury or from the use of certain medicines, including birth control pills and retinoids. They may also form for no known reason inside capillaries(the smallest blood vessels), arteries, veins, or other places on the body. Usually there is only one lesion, but sometimes multiple lesions occur in the same area or the lesions may spread to other areas of the body.
Signs
Pyogenic granulomas are raised, bright red lesions that may be small or large and smooth or bumpy. They grow quickly over weeks to months and may bleed a lot. These lesions are usually on the surface of the skin, but may form in the tissues below the skin and look like other vascular lesions.
Kaposiform hemangioendotheliomas and tufted angiomas usually occur on the skin of the arms and legs, but may also form in deeper tissues, such as muscle or bone, or in the chest or abdomen.
If a physical exam and MRI clearly show the tumor is a kaposiform hemangioendothelioma or a tufted angioma, a biopsy may not be needed. A biopsy is not always done because serious bleeding can occur.
Treatment
Treatment of kaposiform hemangioendotheliomas and tufted angiomas depends on the child's symptoms. Infection, delay in treatment, and surgery can cause bleeding that is life-threatening. Kaposiform hemangioendotheliomas and tufted angiomas are best treated by a vascular anomaly specialist.
Treatment and supportive care to manage bleeding may include the following:
A clinical trial of chemotherapy or targeted therapy (sirolimus).
Even with treatment, these tumors do not fully go away and can come back. Pain and inflammation may get worse with age, often around the time of puberty. Long-term effects include chronic pain, heart failure, bone problems, and lymphedema (the build up of lymph fluid in tissues).
Pseudomyogenic hemangioendothelioma can occur in children, but is most common in men between 20 and 50 years of age. These tumors are rare, and usually occur on or under the skin, or in bone. They may spread to nearby tissue, but usually do not spread to other parts of the body. In most cases, there are multiple tumors.
Signs and Symptoms
Pseudomyogenic hemangioendotheliomas may appear as a lump in soft tissue or may cause pain in the affected area.
Because pseudomyogenic hemangioendothelioma is so rare in children, treatment options are based on clinical trials in adults.
Retiform Hemangioendothelioma
Retiform hemangioendotheliomas are slow growing, flat tumors that occur in young adults and sometimes children. These tumors usually occur on or under the skin of the arms, legs, and trunk. These tumors usually do not spread to other parts of the body.
Composite hemangioendotheliomas have features of both benign and malignantvascular tumors. These tumors usually occur on or under the skin on the arms or legs. They may also occur on the head, neck, or chest. Composite hemangioendotheliomas are not likely to metastasize (spread) but they may come back in the same place. When the tumors metastasize, they usually spread to nearby lymph nodes.
Diagnostic Tests
See the General Information section for a description of tests and procedures used to diagnose composite hemangioendothelioma and find out whether the tumor has spread.
Treatment
Treatment of composite hemangioendotheliomas may include the following:
Lesions in the skin, mouth, or throat. Skin lesions are red, purple, or brown and change from flat, to raised, to scaly areas called plaques, to nodules.
Because Kaposi sarcoma is so rare in children, some treatment options are based on clinical trials in adults. See the PDQ summary on Kaposi Sarcoma Treatment for information about Kaposi sarcoma in adults.
Epithelioid hemangioendotheliomas can occur in children, but are most common in adults between 30 and 50 years of age. They usually occur in the liver, lung, or in bone. They may be fast growing or slow growing. In about a third of cases, the tumor spreads to other parts of the body very quickly.
Tumors that occur in the liver or soft tissue may also cause signs and symptoms.
Diagnostic Tests
Epithelioid hemangioendotheliomas in the liver are found with CT scans and MRI scans. See the General Information section for a description of these tests and procedures used to diagnose epithelioid hemangioendothelioma and find out whether the tumor has spread. X-rays may also be done.
Treatment
Treatment of slow-growing epithelioid hemangioendotheliomas includes the following:
These tumors are very rare in children. Children sometimes have more than one tumor in the skin and/or liver.
Risk Factors
Anything that increases your risk of getting a disease is called a risk factor. Having a risk factor does not mean that you will get the disease; not having risk factors doesn’t mean that you will not get the disease. Talk with your child's doctor if you think your child may be at risk. Risk factors for angiosarcomas include the following:
Physician Data Query (PDQ) is the National Cancer Institute's (NCI's) comprehensive cancer information database. The PDQ database contains summaries of the latest published information on cancer prevention, detection, genetics, treatment, supportive care, and complementary and alternative medicine. Most summaries come in two versions. The health professional versions have detailed information written in technical language. The patient versions are written in easy-to-understand, nontechnical language. Both versions have cancer information that is accurate and up to date and most versions are also available in Spanish.
PDQ is a service of the NCI. The NCI is part of the National Institutes of Health (NIH). NIH is the federal government’s center of biomedical research. The PDQ summaries are based on an independent review of the medical literature. They are not policy statements of the NCI or the NIH.
Purpose of This Summary
This PDQ cancer information summary has current information about the treatment of childhood vascular tumors. It is meant to inform and help patients, families, and caregivers. It does not give formal guidelines or recommendations for making decisions about health care.
Reviewers and Updates
Editorial Boards write the PDQ cancer information summaries and keep them up to date. These Boards are made up of experts in cancer treatment and other specialties related to cancer. The summaries are reviewed regularly and changes are made when there is new information. The date on each summary ("Updated") is the date of the most recent change.
The information in this patient summary was taken from the health professional version, which is reviewed regularly and updated as needed, by the PDQ Pediatric Treatment Editorial Board.
Clinical Trial Information
A clinical trial is a study to answer a scientific question, such as whether one treatment is better than another. Trials are based on past studies and what has been learned in the laboratory. Each trial answers certain scientific questions in order to find new and better ways to help cancer patients. During treatment clinical trials, information is collected about the effects of a new treatment and how well it works. If a clinical trial shows that a new treatment is better than one currently being used, the new treatment may become "standard." Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.
Clinical trials can be found online at NCI's website. For more information, call the Cancer Information Service (CIS), NCI's contact center, at 1-800-4-CANCER (1-800-422-6237).
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