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Adult brain tumors are diseases in which cancer cells begin to grow in the tissues of the brain. Tumors that start in the brain are called primary brain cancer. Tumors that start in another part of the body but spread to the brain are called secondary brain cancer. Secondary brain cancer in adults is more common than primary brain cancer in adults.

Brain Cancer in Adults: Understanding the Brain

The brain controls vital functions, such as memory and learning, the senses (hearing, sight, smell, taste, and touch), and emotion. The brain also controls other parts of the body, including muscles, organs, and blood vessels. The three major parts of the brain, each of which controls different activities, include the: cerebrum, cerebellum brain stem.

Types of Brain Cancer in Adults

There are several types of brain tumors that can occur in adults, which include:

 Brain stem glioma, pineal gland tumor, Astrocytoma.

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Brainstem tumors represent 10% of central nervous system tumors, accounting for 30% of pediatric posterior fossa tumors.

AIMS :

The aim of this study was to clinicopathologically correlate 45 cases of brain stem gliomas and determine the occurrence and prognostic significance of p53 expression. MATERIALS AND

METHOD :

 45 cases of brain stem gliomas encountered during a 19-year period. 30 were diagnosed by surgical biopsy and 15 at autopsy. In 25 cases p53 immunohistochemistry (Avidin Biotinylated technique) was performed. The WHO brain tumor classification and Stroink’s CT classification were applied.

STATISTICAL ANALYSIS USED:

 Chi square test.

RESULTS AND CONCLUSIONS:

 51 % of gliomas were observed in the first decade of life. The female to male ratio was 1.04: 1. The commonest presenting features were cranial nerve palsies (33%) and cerebellar signs (29.8%). 55.55% of cases were located in the pons, 31.01% in the medulla and 13.33% in the midbrain. Diffuse astrocytomas were seen in 40 cases (5% were Grade I, 47.5%Grade II, 32.5% Grade III and 15% Grade IV) and pilocytic astrocytomas in 5 cases. Grade IV patients had 2- 3 mitoses /10 high power fields and had a poorer survival rate.Grade II astrocytomas were treated with excision and radiotherapy, while grade III and IV tumors were treated with radiotherapy and chemotherapy (CCNU). Improvement was noted in 20% of patients postoperatively. The outcome was better in patients who were treated surgically. p53 is a frequently mutated gene in brain stem astrocytomas. It was found in 50 % of glioblastoma multiforme, 28.57% of grade III astrocytoma and 12.5% of grade II astrocytoma, while grade 1 astrocytomas failed to express p53 protein. p53 positivity was more in high grade lesions, decreasing significantly in lower grade lesions.

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Pathophysiology: These tumors have a predilection to originate from the left side. Most are located in the pons; however, medulla and midbrain may be involved as well. Brainstem gliomas are highly aggressive brain tumors. Anatomic location determines the pathophysiological manifestation of the tumor. With tectal lesions, hydrocephalus may occur as a result of fourth ventricular compression. With pontine and cervicomedullary lesions, cranial nerve or long tract signs are observed commonly.

Frequency:

• In the US: Brainstem gliomas have been reported to make up 2.4% of all intracranial tumors in adults and 9.4% of intracranial tumors in children. Brainstem gliomas account for approximately 10-20% of all childhood brain tumors. The incidence in adults is lower than that in children younger than 16 years. A tendency for brainstem gliomas to follow a more indolent course in adults than in children has been noted; in adults, these tumors are more likely to be low grade and remain localized.

Mortality/Morbidity:

• Morbidity is due to the location of the space-occupying lesion and compression of surrounding structures; because these structures regulate basic body functions of blood pressure, respiration, and swallowing as well as motor and sensory functions, compression can produce substantial neurological disability.

• Sudden death can result from increased intracranial pressure and subsequent cerebral herniation. This may be a consequence either of edema induced by the tumor or of hemorrhage into the neoplasm.

Race: CNS tumors vary in incidence by age, sex, ethnic group, and country, and also over time. How much of this variation is due to artifactual influences or etiologic differences has been the subject of many debates.

Sex: Some reports have suggested a slight male preponderance, whereas others have failed to observe any sex predilection.

Age:

• Bimodal age distribution has been noted, with a peak incidence in the latter half of the first decade of life and a second peak in the fourth decade.

• Approximately three fourths of patients are younger than 20 years.

• Neoplasms of the brain stem have been identified in children younger than 1 year.

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Gliomas are a rare but serious type of brain cancer that seem to run in some families.

Purpose of study

Approximately 5% to 10% of glioma cases run in families, but it is not known exactly what genes are related to the disease. Gliogene investigators will look at families with multiple individuals with gliomas in an attempt to identify genetic links among family members.

Finding genetic links may provide information about the disease that can be used to improve treatment and prevention strategies.

“Brain tumor research is extremely challenging, yet rewarding, because any progress in this field translates into significant results down the road,” says Melissa Bondy, Ph.D., principal investigator on the study.

Bondy is professor of epidemiology at M. D. Anderson and director of the Childhood Cancer Epidemiology and Prevention Center – a joint effort of M. D. Anderson, Texas Children’s Hospital and Baylor College of Medicine in Houston.

Study description

Fifteen centers in the United States, United Kingdom, Sweden, Denmark and Israel will participate in Gliogene. More centers may be recruited as the study progresses. The goal is to recruit at least 400 families who have multiple members with gliomas.

“Because so few researchers are tackling the mystery of brain tumor development, the collaboration in this study is very important,” Bondy says.

“By providing a family history and blood sample, patients and their families enable us to better understand the hereditary factors of this disease,” she says. “Participants’ willingness to give minimal time and effort to the Gliogene study may potentially reap dividends for future brain tumor patients.”

The study includes two parts:

1. Researchers will screen approximately 15,000 individuals diagnosed with glioma.

·         This involves completing a five-minute family-history questionnaire.

2. If there are two or more cases of glioma in the family, the individual will be asked to:

·         Complete a 45-minute phone or in-person interview on family history and risk factors

·         Provide a small blood sample for genetic analysis

Participants will be recruited through M. D. Anderson and the collaborating institutions, as well as through the Internet.

All aspects of the study can be completed by phone, e-mail or mail, so participants do not need to live close to collaborating institutions in order to participate. All information collected is kept confidential.

Criteria

To be eligible, families must have two or more biologically related members who have been diagnosed with primary brain tumors known as gliomas.

Background

Gliogene, funded by an $11 million grant from the National Cancer Institute, is the largest genetic study on the causes and risk factors of gliomas.

The Gliogene study is a collaboration among the following institutions in the U.S.:

• M. D. Anderson
• Baylor College of Medicine
• Mayo Clinic
• Memorial Sloan-Kettering Cancer Center
• University of California, San Francisco
• Duke University
• University of Illinois at Chicago
• Evanston Northwestern Healthcare
• Brigham and Women’s Hospital
• Columbia University

These international institutions will participate:

• Umea University Hospital, Sweden
• Institute of Cancer Epidemiology, Denmark
• Institute of Cancer Research, United Kingdom
• Gertner Institute, Israel

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These are the most common symptoms of brain tumors:

• Headaches (usually worse in the morning)
• Nausea or vomiting
• Changes in speech, vision, or hearing
• Problems balancing or walking
• Changes in mood, personality, or ability to concentrate
• Problems with memory
• Muscle jerking or twitching (seizures or convulsions)
• Numbness or tingling in the arms or legs

These symptoms are not sure signs of a brain tumor. Other conditions also could cause these problems. Anyone with these symptoms should see a doctor as soon as possible. Only a doctor can diagnose and treat the problem.

Diagnosis

If a person has symptoms that suggest a brain tumor, the doctor may perform one or more of the following procedures:

Physical exam — The doctor checks general signs of health.

Neurologic exam — The doctor checks for alertness, muscle strength, coordination, reflexes, and response to pain. The doctor also examines the eyes to look for swelling caused by a tumor pressing on the nerve that connects the eye and brain.

CT scan — An x-ray machine linked to a computer takes a series of detailed pictures of the head. The patient may receive an injection of a special dye so the brain shows up clearly in the pictures. The pictures can show tumors in the brain.

RI — A powerful magnet linked to a computer makes detailed pictures of areas inside the body. These pictures are viewed on a monitor and can also be printed. Sometimes a special dye is injected to help show differences in the tissues of the brain. The pictures can show a tumor or other problem in the brain.

The doctor may ask for other tests:

Angiogram — Dye injected into the bloodstream flows into the blood vessels in the brain to make them show up on an x-ray. If a tumor is present, the doctor may be able to see it on the x-ray.

Skull x-ray — Some types of brain tumors cause calcium deposits in the brain or changes in the bones of the skull. With an x-ray, the doctor can check for these changes.

Spinal tap — The doctor may remove a sample of cerebrospinal fluid (the fluid that fills the spaces in and around the brain and spinal cord). This procedure is performed with local anesthesia. The doctor uses a long, thin needle to remove fluid from the spinal column. A spinal tap takes about 30 minutes. The patient must lie flat for several hours afterward to keep from getting a headache. A laboratory checks the fluid for cancer cells or other signs of problems.

Myelogram — This is an x-ray of the spine. A spinal tap is performed to inject a special dye into the cerebrospinal fluid. The patient is tilted to allow the dye to mix with the fluid. This test helps the doctor detect a tumor in the spinal cord.

Biopsy — The removal of tissue to look for tumor cells is called a biopsy. A pathologist looks at the cells under a microscope to check for abnormal cells. A biopsy can show cancer, tissue changes that may lead to cancer, and other conditions. A biopsy is the only sure way to diagnose a brain tumor.

Surgeons can obtain tissue to look for tumor cells in three ways:

• Needle biopsy — The surgeon makes a small incision in the scalp and drills a small hole into the skull. This is called a burr hole. The doctor passes a needle through the burr hole and removes a sample of tissue from the brain tumor.
• Stereotactic biopsy — An imaging device, such as CT or MRI, guides the needle through the burr hole to the location of the tumor. The surgeon withdraws a sample of tissue with the needle.
• Biopsy at the same time as treatment — Sometimes the surgeon takes a tissue sample when the patient has surgery to remove the tumor.

Sometimes a biopsy is not possible. If the tumor is in the brain stem or certain other areas, the surgeon may not be able to remove tissue from the tumor without damaging normal brain tissue. The doctor uses MRI, CT, or other imaging tests instead.

A person who needs a biopsy may want to ask the doctor the following questions:

• Why do I need a biopsy? How will the biopsy affect my treatment plan?
• What kind of biopsy will I have?
• How long will it take? Will I be awake? Will it hurt?
• What are the chances of infection or bleeding after the biopsy? Are there any other risks?
• How soon will I know the results?
• If I do have a brain tumor, who will talk to me about treatment? When?

Treatment

Many people with brain tumors want to take an active part in making decisions about their medical care. They want to learn all they can about their disease and their treatment choices. However, shock and stress after a diagnosis of a brain tumor can make it hard to think of everything to ask the doctor. It often helps to make a list of questions before an appointment. To help remember what the doctor says, patients may take notes or ask whether they may use a tape recorder. Some also want to have a family member or friend with them when they talk to the doctor — to take part in the discussion, to take notes, or just to listen.

The doctor may refer the patient to a specialist, or the patient may ask for a referral. Specialists who treat brain tumors include neurosurgeons, neurooncologists, medical oncologists, and radiation oncologists. The patient may be referred to other health care professionals who work together as a team. The medical team may include a nurse, dietitian, mental health counselor, social worker, physical therapist, occupational therapist, and speech therapist. Children may need tutors to help with schoolwork.

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“In order to keep the cancer from coming back, we need to figure out how to kill that 5 percent of resistant cells,” said Jeremy Rich, M.D., the study’s senior author and a neurologist at Duke University Medical Center in Durham, North Carolina.  Dr. Rich’s work was funded in part by the National Institute of Neurological Disorders and Stroke (NINDS), which also supports Duke’s Specialized Program of Research Excellence (SPORE) in Brain Cancer.

Glioblastoma is the most lethal form of brain cancer, with about half of patients expected to die within a year of diagnosis.  It gets its name from the fact that the cancerous cells have properties of glial cells, which support and nourish the brain’s workhorses, the neurons.  Ionizing radiation, powerful enough to kill cancer cells by breaking apart their DNA, is a common but largely ineffective treatment.  It typically extends life by just a few months.

Dr. Rich’s experiments showed that when mice with glioblastoma were exposed to radiation, cancerous brain cells harboring a surface protein known as CD133 survived the treatment and multiplied, eventually reconstituting the tumor.  When implanted into the brains of healthy mice, CD133+ cells caused glioblastoma. 

CD133+ cells have some of the characteristics of the brain’s normal stem cells – cells that have the capacity to generate brain tissue during embryonic development and, scientists hope, to regenerate brain tissue after injury.

Dr. Rich found that the key to the cells’ resilience is an overactive set of checkpoint proteins – proteins that repair DNA and are somehow mobilized faster in CD133+ cells than in other cells.  Exposing the cells to a chemical inhibitor of checkpoint proteins (before implanting them into mice) left them defenseless against radiation therapy, he showed.  Neither radiation nor the chemical alone could stop the cells from forming tumors in the mice, but the combined treatment all but eradicated them.

Some drug companies are investigating whether checkpoint inhibitors could be developed into drugs to supplement radiation therapy, Dr. Rich said.

In another study published in the same issue of Nature,** Italian researchers showed that bone morphogenetic protein 4 (BMP4), or a drug that mimics its actions, might also become a useful treatment for glioblastoma.  In the normal developing brain, BMP4 directs stem cells to become a type of glial cell.

Led by Angelo Vescovi, Ph.D., a cell biologist at the University of Milan-Bicocca, the Italian group found that pre-exposing CD133+ cells to BMP4 could prevent them from forming tumors when implanted into mice.  Moreover, injecting BMP4 into the brains of mice already seeded with the tumor-forming cells significantly extended the mice’s survival.

Dr. Rich noted that scientists do not understand the origins of the cancerous, CD133+ stem cells or their relationship to normal stem cells.  Still, there is general consensus that “cancer is development gone bad,” he said. 

Jane Fountain, Ph.D., a program director in the NINDS Division of Extramural Research, noted that a growing number of studies are bridging brain cancer research and stem cell research.  “There is great potential that these interactions will lead to breakthroughs in the development of tailored therapeutics for brain tumor patients,” she said.

In the less distant future, parsing CD133+ cells into smaller classes and identifying them in the brains of patients also might allow clinicians to make more accurate assessments about the course of brain cancer and the treatments most likely to be effective in different people.

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Spiritual distress is unresolved religious or spiritual conflict and doubt.

A serious illness like cancer may challenge a patient’s beliefs or religious values, resulting in high levels of spiritual distress. Some cancer patients may feel that cancer is a punishment by God or may suffer a loss of faith after being diagnosed.

Other patients may experience mild spiritual distress when coping with cancer. For example, when prayer is used as a coping method, some patients may worry about how to pray or may doubt their prayers are being answered.

Spiritual and religious well-being may be associated with improved quality of life.

It is not known for sure how spirituality is related to health. Some research shows that spiritual or religious beliefs and practices promote a positive mental attitude that may help a patient feel better. Spiritual and religious well-being may be associated with improved quality of life in the following ways:

·                                  Reduced anxiety, depression, and discomfort.

·                                  Reduced sense of isolation (feeling alone).

·                                  Better adjustment to the effects of cancer and its treatment.

·                                  Increased ability to enjoy life during cancer treatment.

·                                  A feeling of personal growth as a result of living with cancer.

·                                  Improved health outcomes.

Spiritual distress may contribute to poorer health outcomes.

High levels of spiritual distress may interfere with the patient’s ability to cope with cancer and cancer treatment. This distress may contribute to poorer health outcomes and less satisfaction with life. Health care providers may encourage patients to seek advice from appropriate spiritual or religious leaders to help resolve their conflicts, which may improve their health, quality of life, and ability to cope.

 Video  Dr. Sheila Forman- The spiritual needs of cancer patients are not being met during treatment.

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