New Directions for Treating Mesothelioma
Because conventional therapies are not curative for the overwhelming majority of mesothelioma patients, researchers are investigating new types of mesothelioma treatments and therapies. One approach that may yield promising results is anti-angiogenesis. Anti-angiogenesis is a form of therapy that uses drugs or other substances to stop tumors from making new blood vessels. Without a blood supply, the cancers cannot grow effectively. Today, there are several hundred clinical trials of anti-angiogenesis drugs under way. For example, Veglin is an anti-angiogenesis drug undergoing clinical trials at the University of Southern California's Keck School of Medicine. Under the supervision of Parkash S. Gill, M.D. and financed by grants from the Mesothelioma Research Foundation of America, a Phase I study of Veglin has demonstrated some success in patients suffering from lymphoma, sarcoma, and colon and lung cancers. Phase II studies are on-going with the hope they will demonstrate continued clinical efficacy in mesothelioma and other cancers.
Sunday, August 31, 2008
Mesothelioma Treatments and Therapies
Standard treatment for all but localized mesothelioma is generally not curative.1 Surgery and radiotherapy have a limited role in highly selected mesothelioma patients and chemotherapy is the only potential treatment option for the majority of people diagnosed with mesothelioma. Sometimes, these mesothelioma therapies are combined. Despite activity of some chemotherapy, the results are still modest, with a median survival of approximately one year. For individual patients, treatment for mesothelioma depends on the location of the cancer, the stage of the disease, and the patient's age and general health. The only FDA approved chemotherapy for malignant pleural mesothelioma (in combination with cisplatin) is pemetrexed (Alimta). In the key clinical trial that led to its approval for mesothelioma, Alimta was combined with another chemotherapy drug (cisplatin) and compared with cisplatin alone. The median survival for the patients who received both chemotherapy drugs was 12.1 months versus 9.3 months for mesothelioma patients who only received cisplatin.
Orthotic Therapy
Leaders in Effective Treatment Using Orthotics
Orthotics and ankle-foot orthotics (AFOs) are our most useful , effective and versatile treatment. Our podiatrists’ unique credentials make them some of the nation’s most skilled at custom-designing these devices to precisely control function and resolve your problem. The doctors evaluate the biomechanics of your gait themselves, then take a mold of your foot — still the most exacting method — with their own hands. The nation’s highest-tech orthotics lab then creates your devices to high tolerances. We guarantee the comfort of your orthotics, and we can make most needed adjustments right in the office. Drs. Hale and Huppin are committed to providing the best in foot orthotic therapy, and they know that’s a function of their own skill and experience.
What are Orthotics?
The term "orthotic" can refer to almost any device which is worn inside a shoe. Items called “orthotics” can be found in infomercials, retail stores and even at trade shows. There are three very different types of “orthotics” – custom, customized and off-the-shelf. The educated consumer should be aware of each type.
There is a confusing amount of information available on orthotics. For many consumers making an informed decision is difficult. Recognizing a sales pitch and separating it from facts is the key to better health. The information in this section should provide the information you need to make an informed decision.
Orthotics and ankle-foot orthotics (AFOs) are our most useful , effective and versatile treatment. Our podiatrists’ unique credentials make them some of the nation’s most skilled at custom-designing these devices to precisely control function and resolve your problem. The doctors evaluate the biomechanics of your gait themselves, then take a mold of your foot — still the most exacting method — with their own hands. The nation’s highest-tech orthotics lab then creates your devices to high tolerances. We guarantee the comfort of your orthotics, and we can make most needed adjustments right in the office. Drs. Hale and Huppin are committed to providing the best in foot orthotic therapy, and they know that’s a function of their own skill and experience.
What are Orthotics?
The term "orthotic" can refer to almost any device which is worn inside a shoe. Items called “orthotics” can be found in infomercials, retail stores and even at trade shows. There are three very different types of “orthotics” – custom, customized and off-the-shelf. The educated consumer should be aware of each type.
There is a confusing amount of information available on orthotics. For many consumers making an informed decision is difficult. Recognizing a sales pitch and separating it from facts is the key to better health. The information in this section should provide the information you need to make an informed decision.
Thursday, August 21, 2008
Epithelial Mesothelioma Cancer
Epithelial mesothelioma is a rare and deadly form of cancer affects the membrane lining the chest cavity, heart, lungs and abdominal cavity. There are three forms of epithelial mesothelioma: the most common, pleural mesothelioma; the second most common, peritoneal mesothelioma (accounting for only a quarter of the cases) and the rarest form, pericardial mesothelioma.
The vast majority of epithelial mesothelioma cases are the result of asbestos exposure. Indeed, one of the most frustrating aspects of this type of cancer is that patients who develop it were generally exposed 15 to 40 years before hand, which often makes the time and place the disease was contracted difficult to determine.
The early symptoms of epithelial mesothelioma are subtle and somewhat general. Shortness of breath and chest pain are the most common early symptoms. It is because these symptoms are so generic that epithelial mesothelioma is rarely detected early on. Usually when its discovered it is already in an advanced stage and treatment options, particularly localized options such as surgery, are somewhat limited.
If the cancer is in a less advanced stage, aggressive surgery treatments can be sought. Aggressive treatments are treatments aimed at curing the mesothelioma or at least increasing the patients longevity. In some cases an extrapleural pneumonectomy can be performed to try to stop the spread of the mesothelioma.
However this operation is risky and many medical centers will not perform it because of its high mortality rate. Additionally this procedure involves removing an entire lung, as well as extensive epithelial tissue, thereby reducing the patients breathing capacity in half. Even when it is successful it rarely eliminates the mesothelioma, but rather only slows its progress.
Palliative surgery (surgery only aimed at alleviating symptoms) is an option at any stage of the disease. Usually this comes in the form of a "fine needle aspiration" or pleural tap. A pleural tap involves injecting a long needle into the chest or abdomen cavity and draining the pleural space of fluid build up. This procedure may greatly reduces symptoms associated with mesothelioma.
Radiation therapy and chemotherapy are other options. Both are systemic treatments and have the draw back of affecting surrounding tissues as well as cancerous tissues. Radiation therapy is often used in combination with surgery treatments as a way of attempting to remove cancerous growth that could not be removed through surgery. Chemotherapy still has not proved very effective against epithelial mesothelioma but doctors and researcher continue to experiment with new techniques.
The vast majority of epithelial mesothelioma cases are the result of asbestos exposure. Indeed, one of the most frustrating aspects of this type of cancer is that patients who develop it were generally exposed 15 to 40 years before hand, which often makes the time and place the disease was contracted difficult to determine.
The early symptoms of epithelial mesothelioma are subtle and somewhat general. Shortness of breath and chest pain are the most common early symptoms. It is because these symptoms are so generic that epithelial mesothelioma is rarely detected early on. Usually when its discovered it is already in an advanced stage and treatment options, particularly localized options such as surgery, are somewhat limited.
If the cancer is in a less advanced stage, aggressive surgery treatments can be sought. Aggressive treatments are treatments aimed at curing the mesothelioma or at least increasing the patients longevity. In some cases an extrapleural pneumonectomy can be performed to try to stop the spread of the mesothelioma.
However this operation is risky and many medical centers will not perform it because of its high mortality rate. Additionally this procedure involves removing an entire lung, as well as extensive epithelial tissue, thereby reducing the patients breathing capacity in half. Even when it is successful it rarely eliminates the mesothelioma, but rather only slows its progress.
Palliative surgery (surgery only aimed at alleviating symptoms) is an option at any stage of the disease. Usually this comes in the form of a "fine needle aspiration" or pleural tap. A pleural tap involves injecting a long needle into the chest or abdomen cavity and draining the pleural space of fluid build up. This procedure may greatly reduces symptoms associated with mesothelioma.
Radiation therapy and chemotherapy are other options. Both are systemic treatments and have the draw back of affecting surrounding tissues as well as cancerous tissues. Radiation therapy is often used in combination with surgery treatments as a way of attempting to remove cancerous growth that could not be removed through surgery. Chemotherapy still has not proved very effective against epithelial mesothelioma but doctors and researcher continue to experiment with new techniques.
Malignant Mesothelioma
According to The National Cancer Institute, malignant mesothelioma, a rare form of cancer, is a disease in which cancer (malignant) cells are found in the sac lining of the chest (pleura), the abdomen (peritoneum), or the heart (pericardium). Most people diagnosed with mesothelioma have worked on jobs where they breathed asbestos. Asbestos may cause a variety of diseases, from non-cancerous forms such as asbestosis, to much more serious diseases such as mesothelioma. Workers exposed to asbestos in the 1940s, 50s, 60s, and 70s, are coming down with these diseases decades later due to the long latency period associated with all asbestos disease.
The Department of Health and Human Services, the World Health Organization, and the Environmental Protection Agency have determined that asbestos is a human carcinogen. It is well documented that breathing asbestos fibers can increase the risk of cancer in people. Exposure to asbestos has been considered a major occupational health hazard since the first adverse effects were noted in the mid-20th century. At that time, there appeared to be an association between asbestos and lung cancer. Subsequently, it was noted that asbestos also caused pleural thickening. By the 1960s, a definite association between asbestos and mesothelioma, a rare cancer of the lining of the lung or the lining of the abdominal cavity was apparent.
The association between lung cancer and asbestos exposure is now well established. Although in most studies, all histologic types of cancer are seen, there appears to be a preponderance of adenocarcinoma. Lung cancer in asbestos-exposed workers is thought to occur at a slightly younger age than other lung cancers, and these cancers are more commonly located in the lower lobes of the lungs. There is what is called a "synergistic effect" between cigarette smoking and asbestos exposure, thus the risk of getting lung cancer rises to extraordinarily high levels if the exposed person is also a smoker. If you have been exposed to asbestos, you should stop smoking. This may be the most important action you can take to improve your health and decrease your risk of lung cancer.
The risk of non-cancerous asbestos-related diseases generally increases with increasing levels of exposure, however, this dose-response relationship is less clear for mesothelioma, where even short-term occupational exposure, or secondary household exposure occur. Cigarette smoking has no relationship to mesothelioma. We are all exposed to asbestos in the air we breathe, however, these levels are generally considered "acceptable". There has been no correlation drawn as to why, given the same set of circumstances and amounts of exposure, one person contracts mesothelioma and the person next to them does not, or why the more heavily exposed individual never contracts an asbestos-related disease, yet his wife is diagnosed after washing his work clothing.
Your Question or Comment:
The Department of Health and Human Services, the World Health Organization, and the Environmental Protection Agency have determined that asbestos is a human carcinogen. It is well documented that breathing asbestos fibers can increase the risk of cancer in people. Exposure to asbestos has been considered a major occupational health hazard since the first adverse effects were noted in the mid-20th century. At that time, there appeared to be an association between asbestos and lung cancer. Subsequently, it was noted that asbestos also caused pleural thickening. By the 1960s, a definite association between asbestos and mesothelioma, a rare cancer of the lining of the lung or the lining of the abdominal cavity was apparent.
The association between lung cancer and asbestos exposure is now well established. Although in most studies, all histologic types of cancer are seen, there appears to be a preponderance of adenocarcinoma. Lung cancer in asbestos-exposed workers is thought to occur at a slightly younger age than other lung cancers, and these cancers are more commonly located in the lower lobes of the lungs. There is what is called a "synergistic effect" between cigarette smoking and asbestos exposure, thus the risk of getting lung cancer rises to extraordinarily high levels if the exposed person is also a smoker. If you have been exposed to asbestos, you should stop smoking. This may be the most important action you can take to improve your health and decrease your risk of lung cancer.
The risk of non-cancerous asbestos-related diseases generally increases with increasing levels of exposure, however, this dose-response relationship is less clear for mesothelioma, where even short-term occupational exposure, or secondary household exposure occur. Cigarette smoking has no relationship to mesothelioma. We are all exposed to asbestos in the air we breathe, however, these levels are generally considered "acceptable". There has been no correlation drawn as to why, given the same set of circumstances and amounts of exposure, one person contracts mesothelioma and the person next to them does not, or why the more heavily exposed individual never contracts an asbestos-related disease, yet his wife is diagnosed after washing his work clothing.
Your Question or Comment:
Clinical Trial Basic
Clinical trials are studies of the safety and/or effectiveness of new drugs being tested on humans. For mesothelioma, trials are being conducted to find a better and more effective means of treatment. Anyone interested in participating in a clinical trial should discuss the particular trial thoroughly with their doctor before a making a decision on whether it is right for them.
All clinical trials carry potential benefits and risks, and it is important that you have a complete understanding of what you might expect. For instance, since clinical trials are often conducted at larger cancer centers, in many cases, travel may be necessary to receive treatment and routine tests. On the other hand, care is provided at top-notch facilities by physicians who are leaders in the field of cancer research. Another benefit would be having access to the new drug before it is widely available, however, the new drug may ultimately be proven not as effective as the “standard” of care.
Eligibility requirements for clinical trials are not the same; each study has specific guidelines to participate. Some trials allow participation after other treatments have failed, while others require that the patient have no prior treatment. Your doctor should be able to advise you which trial might be the best fit in your particular case.
Some treatment trials are “randomized”, meaning the new treatment is compared with a current standard of treatment. Depending on which arm of the protocol you are assigned, you may receive the new treatment or the standard. You should be informed in advance of this eventuality by the doctor conducting the trial. Placebos (pills that contain no active ingredient) are rarely used in cancer trials.
All clinical trials carry potential benefits and risks, and it is important that you have a complete understanding of what you might expect. For instance, since clinical trials are often conducted at larger cancer centers, in many cases, travel may be necessary to receive treatment and routine tests. On the other hand, care is provided at top-notch facilities by physicians who are leaders in the field of cancer research. Another benefit would be having access to the new drug before it is widely available, however, the new drug may ultimately be proven not as effective as the “standard” of care.
Eligibility requirements for clinical trials are not the same; each study has specific guidelines to participate. Some trials allow participation after other treatments have failed, while others require that the patient have no prior treatment. Your doctor should be able to advise you which trial might be the best fit in your particular case.
Some treatment trials are “randomized”, meaning the new treatment is compared with a current standard of treatment. Depending on which arm of the protocol you are assigned, you may receive the new treatment or the standard. You should be informed in advance of this eventuality by the doctor conducting the trial. Placebos (pills that contain no active ingredient) are rarely used in cancer trials.
Powers of Attorney
A Power of Attorney (POA) is a written document in which you (“the Principal”)designate another person (“the Agent or Attorney-in-Fact”) to act on your behalf in making property, financial and other legal decisions. The most common types of Powers of Attorney include:
* Durable Power of Attorney
A Durable Power of Attorney allows the Agent or Attorney-in-Fact to act for the Principal even after the Principal is not mentally competent or physically able to make decisions. The Durable Power of Attorney may be used immediately, and is effective until it is revoked by the Principal, or until the Principal’s death.
* Nondurable Power of Attorney
A Nondurable Power of Attorney is often used for a specific transaction, such as the closing on the sale of a residence, or the handling of the Principal’s financial affairs while the Principal is traveling out of the country. A Nondurable Power of Attorney takes effect immediately and remains in effect until it is revoked by the Principal, or until the Principal becomes mentally incompetent or dies.
* Springing Power of Attorney
A Springing Power of Attorney becomes effective at a future time when an Agent, or another third party, such as the Principal’s physician, determines that the Principal in no longer competent to handles his or her own financial affairs. A Springing Power of Attorney remains in effect until the Principal’s death, or until revoked by a court.
Powers of Attorney are important legal documents, and should be given only after careful consideration. A licensed attorney in your state can:
* Provide you with advice about the powers that are appropriate to be delegated
* Provide counsel on the choice of an Agent.
* Outline the Agent’s legal and fiduciary obligations while acting under a Power of Attorney.
* Ensure that the Power of Attorney is properly executed and meets all legal requirements.
* Durable Power of Attorney
A Durable Power of Attorney allows the Agent or Attorney-in-Fact to act for the Principal even after the Principal is not mentally competent or physically able to make decisions. The Durable Power of Attorney may be used immediately, and is effective until it is revoked by the Principal, or until the Principal’s death.
* Nondurable Power of Attorney
A Nondurable Power of Attorney is often used for a specific transaction, such as the closing on the sale of a residence, or the handling of the Principal’s financial affairs while the Principal is traveling out of the country. A Nondurable Power of Attorney takes effect immediately and remains in effect until it is revoked by the Principal, or until the Principal becomes mentally incompetent or dies.
* Springing Power of Attorney
A Springing Power of Attorney becomes effective at a future time when an Agent, or another third party, such as the Principal’s physician, determines that the Principal in no longer competent to handles his or her own financial affairs. A Springing Power of Attorney remains in effect until the Principal’s death, or until revoked by a court.
Powers of Attorney are important legal documents, and should be given only after careful consideration. A licensed attorney in your state can:
* Provide you with advice about the powers that are appropriate to be delegated
* Provide counsel on the choice of an Agent.
* Outline the Agent’s legal and fiduciary obligations while acting under a Power of Attorney.
* Ensure that the Power of Attorney is properly executed and meets all legal requirements.
Symptoms Managed through Palliative Care
Some of the common symptoms managed through palliative care include:
* Pain
* Shortness of breath
* Fatigue
* Dry Mouth
* Loss of appetite
* Gastrointestinal problems
* Skin problems
* Anxiety/Depression
Pain
Pain management is one of the most important aspects of palliative care. Because it is now considered a medical specialty, you may wish to consult a physician well versed in pain management if your physician seems unable or unwilling to provide adequate pain control.
Many people with cancer experience pain. Statistics show that 30 to 40 per cent of patients in active cancer therapy, and 70 to 90 percent of patients with advanced cancer report pain. In most cases, pain can be controlled through medications prescribed according to the World Health Organization's Analgesic Ladder, an approach using various levels of medication based on the severity of pain. This type of pain treatment, using drugs, is called pharmacological therapy. Medications may include innon-opioid pain relievers, opioid pain relievers, adjuvant medications (those whose primary purpose is not for pain, but for other conditions), and topical treatments such as a patch, gel, or cream. A study published the Annals of Oncology found a reluctance among cancer patients to take opioid medications due to a belief that such medications are offerred only at the end of life.
Non-pharmacological therapies, those that do not rely primarily on medication to achieve effect, include therapeutic exercise and cognitive behavioral techniques such as deep breathing, muscle relaxation, imagery, meditation, biofeedback therapy, and distraction. Complementary and/or alternative approaches include acupuncture and massage therapy. Integretive medicine refers to the combination of mainstream conventional treatment such as surgery, chemotherapy and radiation with complementary therapies proven to have sound scientific evidence as to their safety and effectiveness.
Shortness of Breath
Shortness of breath, or dyspnea, affects 20 to 80 percent of palliative care patients. Causes of this condition may include, lung disease, fluid in the lungs, infection, anemia, or emotional factors such as anxiety. While medications or oxygen may be used to treat shortness of breath, sometimes measures such as changing position, using relaxation techniques, or improving air circulation may help. More on anemia from chemotherapy treatment.
Fatigue
Cancer-related fatigue may be the result of the general progression of the disease, the effects of medication, or the after effects of treatments such as surgery, chemotherapy, or radiation therapy. The following symptoms are usually associated with fatigue:
* Diminished energy level disproportionate to activity
* Diminished activity associated with physical or intellectual performance
* Diminished motivation; lack of interest in activities
* Exhaustion, apathy, or lethargy
* Generalized tiredness
* Sleep abnormalities
* Irritability, impatience, or changes in mood
The treatment of fatigue is based on first identifying, and then managing, the underlying cause of the fatigue. Once that is accomplished, interventions such as medication, exercise, stress management, and nutrition are used. More on fatigue in mesothelioma patients.
Dry Mouth
Dry mouth, or xerostoma, is another symptom addressed in palliative care. Causes may be dehydration, depression or anxiety, or may be a side effect of medications such as pain relievers, antidepressants, diuretics, or tranquilizers. Chemotherapy treatments or radiotherapy may also be a cause.
Relief of dry mouth can often be achieved by:
* Drinking plenty of fluids
* Sucking on ice chips or Vitamin C tablets
* Chewing sugarless gum
* Maintaining good oral hygiene
* Providing humidified air
Loss of Appetite
Patients with life-threatening illnesses often lose their appetite, and subsequently, lose weight. If the condition becomes too severe, it is called cachexia. Doctors uniformly agree that nutrition plays a vital role in the patient's well being. Causes of weight loss include inadequate intake of nutrients because the patient can not or does not want to eat, poor absorption of the food that is eaten, and changes in the patient's metabolism.
Weight loss may be managed by:
* Eating smaller, more frequent meals
* Eating high calorie, high protein foods
* Receiving nutritional counseling
There are also medications which may help depending on the patient's desired goal. Some of these medications stimulate appetite, but do not usually increase weight, some stimulate appetite and cause slight weight gain, and still others help prevent nausea and vomiting.
Gastrointestinal Problems
Gastrointestinal problems may be associated with the disease process itself, or as a side effect of treatments or medications the patient is receiving. These may include nausea, vomiting, constipation, and diarrhea.
As mentioned above, there are medications which can help with nausea and vomiting. Your doctor or a nutritionist may also be able to provide eating hints and/or special diets tailored to fit the patient's individual needs. More on diarreah in mesothelioma patients.
Skin Problems
There are a variety of skin problems which may accompany cancer, including dryness, itching, rash, sores, and ulcers. It is important to treat these conditions as quickly as possible in order to reduce discomfort and the risk of infection.
* Dryness may be lessened by adding baby or mineral oil to warm bath water, and by applying moisturizers. It is also important to drink 8-10 glasses of water per day.
* Itching and rash may be lessened by adding baking soda to cool bath water, or by applying a cool, moist cloth to itchy areas. Avoid harsh laundry detergents, and change sheets and towels daily.
* Keep skin clean and dry and check skin daily for pressure sores or ulcers which may become infected.
Anxiety/Depression
Anxiety is a hallmark of a life-threatening illness. Feelings of fear, worry, or apprehension may lead to long-term generalized anxiety, or short, intense panic attacks. Causes may include difficulty in coming to terms with the illness, fear of isolation and separation, poorly controlled pain, or side effects of medication.
Treatments to control anxiety may include stress management techniques, counseling, support of family and friends, and control of pain or side effects from medication.
Depression, while less common, often affects family members as well as the patient themselves. Depression may be related to loss of the ability to function, changing family roles, limited social and financial support, pain, or other symptoms such as shortness of breath.
Control of the above symptoms is accomplished through antidepressant medication, support and counseling, pain management, and stress management.
* Pain
* Shortness of breath
* Fatigue
* Dry Mouth
* Loss of appetite
* Gastrointestinal problems
* Skin problems
* Anxiety/Depression
Pain
Pain management is one of the most important aspects of palliative care. Because it is now considered a medical specialty, you may wish to consult a physician well versed in pain management if your physician seems unable or unwilling to provide adequate pain control.
Many people with cancer experience pain. Statistics show that 30 to 40 per cent of patients in active cancer therapy, and 70 to 90 percent of patients with advanced cancer report pain. In most cases, pain can be controlled through medications prescribed according to the World Health Organization's Analgesic Ladder, an approach using various levels of medication based on the severity of pain. This type of pain treatment, using drugs, is called pharmacological therapy. Medications may include innon-opioid pain relievers, opioid pain relievers, adjuvant medications (those whose primary purpose is not for pain, but for other conditions), and topical treatments such as a patch, gel, or cream. A study published the Annals of Oncology found a reluctance among cancer patients to take opioid medications due to a belief that such medications are offerred only at the end of life.
Non-pharmacological therapies, those that do not rely primarily on medication to achieve effect, include therapeutic exercise and cognitive behavioral techniques such as deep breathing, muscle relaxation, imagery, meditation, biofeedback therapy, and distraction. Complementary and/or alternative approaches include acupuncture and massage therapy. Integretive medicine refers to the combination of mainstream conventional treatment such as surgery, chemotherapy and radiation with complementary therapies proven to have sound scientific evidence as to their safety and effectiveness.
Shortness of Breath
Shortness of breath, or dyspnea, affects 20 to 80 percent of palliative care patients. Causes of this condition may include, lung disease, fluid in the lungs, infection, anemia, or emotional factors such as anxiety. While medications or oxygen may be used to treat shortness of breath, sometimes measures such as changing position, using relaxation techniques, or improving air circulation may help. More on anemia from chemotherapy treatment.
Fatigue
Cancer-related fatigue may be the result of the general progression of the disease, the effects of medication, or the after effects of treatments such as surgery, chemotherapy, or radiation therapy. The following symptoms are usually associated with fatigue:
* Diminished energy level disproportionate to activity
* Diminished activity associated with physical or intellectual performance
* Diminished motivation; lack of interest in activities
* Exhaustion, apathy, or lethargy
* Generalized tiredness
* Sleep abnormalities
* Irritability, impatience, or changes in mood
The treatment of fatigue is based on first identifying, and then managing, the underlying cause of the fatigue. Once that is accomplished, interventions such as medication, exercise, stress management, and nutrition are used. More on fatigue in mesothelioma patients.
Dry Mouth
Dry mouth, or xerostoma, is another symptom addressed in palliative care. Causes may be dehydration, depression or anxiety, or may be a side effect of medications such as pain relievers, antidepressants, diuretics, or tranquilizers. Chemotherapy treatments or radiotherapy may also be a cause.
Relief of dry mouth can often be achieved by:
* Drinking plenty of fluids
* Sucking on ice chips or Vitamin C tablets
* Chewing sugarless gum
* Maintaining good oral hygiene
* Providing humidified air
Loss of Appetite
Patients with life-threatening illnesses often lose their appetite, and subsequently, lose weight. If the condition becomes too severe, it is called cachexia. Doctors uniformly agree that nutrition plays a vital role in the patient's well being. Causes of weight loss include inadequate intake of nutrients because the patient can not or does not want to eat, poor absorption of the food that is eaten, and changes in the patient's metabolism.
Weight loss may be managed by:
* Eating smaller, more frequent meals
* Eating high calorie, high protein foods
* Receiving nutritional counseling
There are also medications which may help depending on the patient's desired goal. Some of these medications stimulate appetite, but do not usually increase weight, some stimulate appetite and cause slight weight gain, and still others help prevent nausea and vomiting.
Gastrointestinal Problems
Gastrointestinal problems may be associated with the disease process itself, or as a side effect of treatments or medications the patient is receiving. These may include nausea, vomiting, constipation, and diarrhea.
As mentioned above, there are medications which can help with nausea and vomiting. Your doctor or a nutritionist may also be able to provide eating hints and/or special diets tailored to fit the patient's individual needs. More on diarreah in mesothelioma patients.
Skin Problems
There are a variety of skin problems which may accompany cancer, including dryness, itching, rash, sores, and ulcers. It is important to treat these conditions as quickly as possible in order to reduce discomfort and the risk of infection.
* Dryness may be lessened by adding baby or mineral oil to warm bath water, and by applying moisturizers. It is also important to drink 8-10 glasses of water per day.
* Itching and rash may be lessened by adding baking soda to cool bath water, or by applying a cool, moist cloth to itchy areas. Avoid harsh laundry detergents, and change sheets and towels daily.
* Keep skin clean and dry and check skin daily for pressure sores or ulcers which may become infected.
Anxiety/Depression
Anxiety is a hallmark of a life-threatening illness. Feelings of fear, worry, or apprehension may lead to long-term generalized anxiety, or short, intense panic attacks. Causes may include difficulty in coming to terms with the illness, fear of isolation and separation, poorly controlled pain, or side effects of medication.
Treatments to control anxiety may include stress management techniques, counseling, support of family and friends, and control of pain or side effects from medication.
Depression, while less common, often affects family members as well as the patient themselves. Depression may be related to loss of the ability to function, changing family roles, limited social and financial support, pain, or other symptoms such as shortness of breath.
Control of the above symptoms is accomplished through antidepressant medication, support and counseling, pain management, and stress management.
Ascites and Peritoneal Cavity Fluid
Ascites build up inside the abdomen in a membrane called the peritoneum. This membrane consists of two layers, one that lines the abdominal wall and one that encloses the organs of the abdomen. The peritoneum produces a fluid that serves as a lubricant allowing the organs of the abdomen to glide easily over one another. Usually this fluid is present in a very small quantity. Ascites is the build up, or overabundance of this fluid and is often the first tangible indication that mesothelioma is present in the body, it the most common early sign of peritoneal mesothelioma.
The symptoms of ascites are unpleasant. Usually the stomach becomes bloated and sometimes pain, and nausea accompanies this bloating. Its not uncommon for patients to experience a loss of appetite, or for sitting, standing, and walking to become restricted and uncomfortable. Fatigue, lethargy and breathlessness are also possible symptoms.
When ascites is first detected, the treating doctor will drain the fluid in a procedure known as a Paracentesis. By draining the fluid doctor's can reduce symptoms caused by the build up as well as gather a sample to learn the reason for its occurrence. A paracentesis is a relatively easy procedure that can take place in the hospital bed or in the outpatient clinic. Occasionally doctors will perform the procedure in the ultra sound department so that they can more easily locate the fluid build up. Ultra sounds are particularly useful when fluid has collected in multiple pockets, as will sometimes occur when the ascitic build up is smaller.
After the doctor injects the patient with a local anesthesia he will make a small incision in the abdomen wall in order to pass a cannula into the abdomen. The cannula is a thin tube that is attached to drainage bag for the paracentesis. Using gentle suction the doctor will draw the ascitic fluid from the abdomen into the drainage bag. If there is only a small amount of ascitic fluid the procedure can usually be accomplished in an outpatient setting, if there is a larger amount, however, the drain may remain in place for two to three days.
At the beginning of the paracentesis up to a liter of fluid may be drained quickly and safely. After this initial amount, however, the drain must be performed slowly because a sudden release of abdominal pressure may cause blood pressure to drop as well. During the procedure doctors will monitor the heart rate of the patient to make sure this doesn't occur. Sometimes during the procedure the drain will become blocked, but often the solution is just a matter of the patient repositioning him or herself (sitting up, lying back etc.). Occasionally the cannula can be a source of infection (a variation in blood pressure will tell doctors if this is the case).
If a patient has been diagnosed with ascites but the cause has not yet been determined, it is very possible that the ascites is not a result of mesothelioma. Cirrhosis is the most common cause of the ascites build up, accounting for 80% of its occurrences. Tuberculosis, endometriosis, Familial Mediterranean fever, Whipple's disease, are all possible causes of ascites. Generally speaking cancer is the cause of ascitic build up only 10 % of the time.
The symptoms of ascites are unpleasant. Usually the stomach becomes bloated and sometimes pain, and nausea accompanies this bloating. Its not uncommon for patients to experience a loss of appetite, or for sitting, standing, and walking to become restricted and uncomfortable. Fatigue, lethargy and breathlessness are also possible symptoms.
When ascites is first detected, the treating doctor will drain the fluid in a procedure known as a Paracentesis. By draining the fluid doctor's can reduce symptoms caused by the build up as well as gather a sample to learn the reason for its occurrence. A paracentesis is a relatively easy procedure that can take place in the hospital bed or in the outpatient clinic. Occasionally doctors will perform the procedure in the ultra sound department so that they can more easily locate the fluid build up. Ultra sounds are particularly useful when fluid has collected in multiple pockets, as will sometimes occur when the ascitic build up is smaller.
After the doctor injects the patient with a local anesthesia he will make a small incision in the abdomen wall in order to pass a cannula into the abdomen. The cannula is a thin tube that is attached to drainage bag for the paracentesis. Using gentle suction the doctor will draw the ascitic fluid from the abdomen into the drainage bag. If there is only a small amount of ascitic fluid the procedure can usually be accomplished in an outpatient setting, if there is a larger amount, however, the drain may remain in place for two to three days.
At the beginning of the paracentesis up to a liter of fluid may be drained quickly and safely. After this initial amount, however, the drain must be performed slowly because a sudden release of abdominal pressure may cause blood pressure to drop as well. During the procedure doctors will monitor the heart rate of the patient to make sure this doesn't occur. Sometimes during the procedure the drain will become blocked, but often the solution is just a matter of the patient repositioning him or herself (sitting up, lying back etc.). Occasionally the cannula can be a source of infection (a variation in blood pressure will tell doctors if this is the case).
If a patient has been diagnosed with ascites but the cause has not yet been determined, it is very possible that the ascites is not a result of mesothelioma. Cirrhosis is the most common cause of the ascites build up, accounting for 80% of its occurrences. Tuberculosis, endometriosis, Familial Mediterranean fever, Whipple's disease, are all possible causes of ascites. Generally speaking cancer is the cause of ascitic build up only 10 % of the time.
Unconventional methods
Unconventional methods of cancer treatment make claims that can not be scientifically substantiated. They commonly claim to be effective against cancers that are considered incurable, and tout treatments with relatively few, if any, side effects.
The use of these unconventional methods may result in the loss of valuable time and the opportunity to receive potentially effective therapy. It is always important to remain in the care of a qualified physician who uses accepted methods of treatment or who is participating in scientifically designed investigational therapies.
The use of these unconventional methods may result in the loss of valuable time and the opportunity to receive potentially effective therapy. It is always important to remain in the care of a qualified physician who uses accepted methods of treatment or who is participating in scientifically designed investigational therapies.
Alternative medicine
Complementary and alternative medicine covers a wide range of healing philosophies that conventional medicine does not commonly accept or make available to its patients. Some of these practices include the use of acupuncture, herbs, homeopathy, therapeutic massage, and Far Eastern medicine to treat health conditions.
These therapies may be used alone as an alternative to conventional medicine, or in addition to conventional medicine, in which case they are referred to as complementary. Many are considered holistic, meaning their focus is to treat the whole patient - physically, mentally, emotionally, and spiritually. These treatments are not widely taught as a part of the medical curriculum, are not generally used in hospitals, and, for the most part, are not covered under insurance policies.
Many cancer patients try various complementary and/or alternative medicine techniques during the course of their treatment, and although they may not work for everyone, some patients benefit by managing their symptoms or side effects. One important caveat, is to discuss any complementary or alternative treatments you may be considering with your doctor to be sure nothing interferes with your conventional care. For instance, dietary supplements such as herbs or vitamins may be "natural", but not necessarily "safe". They may lessen the effectiveness of certain anticancer drugs, or when taken with other drugs or in large doses, may actually cause harm. Since supplements of this nature are not governed by the FDA (Food and Drug Administration), and a prescription is not necessary to purchase, it is up to the consumer to make informed and conscientious decisions regarding their use.
These therapies may be used alone as an alternative to conventional medicine, or in addition to conventional medicine, in which case they are referred to as complementary. Many are considered holistic, meaning their focus is to treat the whole patient - physically, mentally, emotionally, and spiritually. These treatments are not widely taught as a part of the medical curriculum, are not generally used in hospitals, and, for the most part, are not covered under insurance policies.
Many cancer patients try various complementary and/or alternative medicine techniques during the course of their treatment, and although they may not work for everyone, some patients benefit by managing their symptoms or side effects. One important caveat, is to discuss any complementary or alternative treatments you may be considering with your doctor to be sure nothing interferes with your conventional care. For instance, dietary supplements such as herbs or vitamins may be "natural", but not necessarily "safe". They may lessen the effectiveness of certain anticancer drugs, or when taken with other drugs or in large doses, may actually cause harm. Since supplements of this nature are not governed by the FDA (Food and Drug Administration), and a prescription is not necessary to purchase, it is up to the consumer to make informed and conscientious decisions regarding their use.
Gene therapy
Gene therapy is an approach to treating potentially fatal or disabling diseases by modifying the expression of an individual's genes toward a therapeutic goal. The premise of gene therapy is based on correcting disease at the DNA level and compensating for the abnormal genes.
Replacement gene therapy replaces a mutated or missing gene, most often a tumor suppressor gene, with a normal copy of that gene which serves to keep cell growth and division under control. The p53 gene, the most common gene mutated in cancer has become a prime target for gene replacement, and has met with some success in inhibiting cell growth, inhibiting angiogenesis (the development of a tumor's blood supply), and inducing apoptosis (cell death).
Knockout gene therapy targets the products of oncogenes (a gene that can induce tumor formation) in an effort to render them inactive and reduce cell growth.
Replacement gene therapy replaces a mutated or missing gene, most often a tumor suppressor gene, with a normal copy of that gene which serves to keep cell growth and division under control. The p53 gene, the most common gene mutated in cancer has become a prime target for gene replacement, and has met with some success in inhibiting cell growth, inhibiting angiogenesis (the development of a tumor's blood supply), and inducing apoptosis (cell death).
Knockout gene therapy targets the products of oncogenes (a gene that can induce tumor formation) in an effort to render them inactive and reduce cell growth.
Photodynamic therapy
Photodynamic therapy (PDT) is a type of cancer treatment based on the premise that single-celled organisms, if first treated with certain photosensitive drugs, will die when exposed to light at a particular frequency. PDT destroys cancerous cells by using this fixed frequency light to activate photosensitizing drugs which have accumulated in body tissues.
In PDT, a photosensitizing drug is administered intravenously. Within a specific time frame (usually a matter of days), the drug selectively concentrates in diseased cells, while rapidly being eliminated from normal cells. The treated cancer cells are then exposed to a laser light chosen for its ability to activate the photosensitizing agent. This laser light is delivered to the cancer site, (in the case of mesothelioma, the pleura), through a fiberoptic device that allows the laser light to be manipulated by the physician. As the agent in the treated cells absorbs the light, an active form of oxygen destroys the surrounding cancer cells. The light exposure must be carefully timed, so that it occurs when most of the photosensitizing drug has left the healthy cells, but is still present in cancerous ones.
The major side effect of PDT is skin sensitivity. Patients undergoing this type of therapy are usually advised to avoid direct and even indirect sunlight for at least six weeks. Other side effects may include nausea, vomiting, a metallic taste in the mouth, and eye sensitivity to light. These symptoms may sometimes come as a result of the injection of the photosensitizing agent.
In PDT, a photosensitizing drug is administered intravenously. Within a specific time frame (usually a matter of days), the drug selectively concentrates in diseased cells, while rapidly being eliminated from normal cells. The treated cancer cells are then exposed to a laser light chosen for its ability to activate the photosensitizing agent. This laser light is delivered to the cancer site, (in the case of mesothelioma, the pleura), through a fiberoptic device that allows the laser light to be manipulated by the physician. As the agent in the treated cells absorbs the light, an active form of oxygen destroys the surrounding cancer cells. The light exposure must be carefully timed, so that it occurs when most of the photosensitizing drug has left the healthy cells, but is still present in cancerous ones.
The major side effect of PDT is skin sensitivity. Patients undergoing this type of therapy are usually advised to avoid direct and even indirect sunlight for at least six weeks. Other side effects may include nausea, vomiting, a metallic taste in the mouth, and eye sensitivity to light. These symptoms may sometimes come as a result of the injection of the photosensitizing agent.
Malignant Pleural Mesothelioma Updates
Malignant pleural mesothelioma (MPM) is a tumor that arises from the surfaces of the pleural and peritoneal cavities, the pericardium, or the tunica vaginalis. There are over 2,000 cases in the United States each year, with about 80% originating from the pleura.[1] Patients with MPM most commonly present with symptoms of dyspnea or pleuritic chest pain. Chest roentgenograms will often show a unilateral pleural effusion. In addition, in light of the association between mesothelioma and asbestos exposure, many plain films in MPM will also exhibit pleural plaques.
To date, treatment options have been limited. A small minority of mesothelioma patients may be appropriate for surgical intervention and multimodality therapy. For those patients with unresectable disease, systemic treatment with chemotherapy has achieved some success. Recent efforts have focused on exploring the role of multimodality therapy, improving patient selection for this aggressive strategy, and investigating new agents and new combinations of systemic therapies in MPM. Here we review recent data presented at the 2007 ASCO Meeting (Chicago, IL, June 2007) and at the 12th World Conference on Lung Cancer (Seoul, South Korea, September 2007).
Role of Surgery
The role of surgery in the management of MPM remains unclear. As yet, there have been no published randomized results comparing surgery to nonoperative management with conventional chemotherapy. However, among the case series that exist, there have been some encouraging preliminary results. In a case series published by Sugarbaker et al., there was a group of 31 patients who had epithelioid histology, clear resection margins, and no extrapleural nodes.[2] For this specific group, median survival was 51 months. These results have encouraged investigators at a number of centers to attempt to refine both the optimum treatment regimen and the selection of appropriate patients.
At the ASCO 2007 Meeting in Chicago, IL, Krug et al. presented results of a multi-center Phase II feasibility study of trimodality therapy.[3] Eligible patients had T1-3, N0-2, M0 malignant pleural mesothelioma, demonstrated good performance status (ECOG PS 0-1), were treatment-naïve, and had a post-operative FEV1 > 35%. Planned therapy included four cycles of cisplatin and pemetrexed. Following chemotherapy, non-progressing patients underwent extrapleural pneumonectomy followed by hemithoracic radiation to a total of 54 Gy. The 75 patients enrolled in the trial were predominantly male (70%) and most had epithelioid histology (80%). A total of 87% completed the planned four cycles of chemotherapy. Fifty-six patients (75%) eventually proceeded to extrapleural pneumonectomy (EPP), with 42 patients (56%) subsequently receiving radiation. Median time to progression for the entire group was 13.1 months, with a median overall survival of 16.6 months.
More recently, at the 12th World Conference on Lung Cancer in Seoul, South Korea, Smith et al. presented the results of a retrospective analysis of MPM patients at the Ottawa Hospital Regional Cancer Center.[4] A total of 147 MPM patients were identified. Multivariate analysis showed higher tumor stage, weight loss, poorer performance status, and an elevated platelet count to be independently associated with poor prognosis. In addition, the authors performed a case control analysis comparing MPM patients who underwent extrapleural pneumonectomy (n=15) with matched controls who did not undergo the radical surgery. Patients undergoing EPP had a median overall survival of 25.4 months (95% CI 12.2 – 43.6), with the result approaching but not reaching statistical significance compared with matched controls (p=0.007).
Systemic Therapy
With the publication of the EMPHACIS trial in 2003, combination treatment with cisplatin plus pemetrexed became the standard first-line therapy for patients with MPM.[5] In that study, patients were randomized to receive cisplatin alone vs. cisplatin plus pemetrexed. Median time to progression favored the combination therapy arm (5.7 months vs. 3.9 months, p=0.001); median overall survival also showed a benefit for patients treated with the two-drug regimen (12.1 months vs. 9.3 months, p = 0.02).
Pemetrexed and pemetrexed-based combinations
In the last six months, investigators have presented several analyses from the pemetrexed International Expanded Access Program (EAP). At the 2007 ASCO Meeting, Santoro et al. presented a comparison of pemetrexed plus cisplatin (P+Cis) vs. pemetrexed plus carboplatin (P + Cb).[6] In this retrospective, non-randomized comparison, the two arms demonstrated similar response rates (26% for P+Cis, 22% for P+Cb) and one-year survival rates (63% and 64%, respectively). Median survival for each group could not be estimated due to the high number of censored patients.
More recently, the same authors presented results of a 3-arm, non-randomized, open-label study of pemetrexed alone (P), pemetrexed plus cisplatin (P+Cis), and pemetrexed plus carboplatin (P+Cb) in chemo-naïve patients who were treated as part of the EAP.[7] Not surprisingly, the pemetrexed arm of this nonrandomized study contained a greater proportion of patients with poorer performance status. While pemetrexed monotherapy was associated with a lower treatment response rate, all three arms showed similar one-year survival rates and median time to disease progression.
Vinorelbine plus a platinum agent
Investigators from Denmark have explored the use of vinorelbine, rather than pemetrexed, in combination with a platinum agent. Dr. Sorensen et al. recently presented the results of two such nonrandomized Phase II studies at the 12th World Conference on Lung Cancer. The first, conducted from 2003 – 2006, treated 57 MPM patients with cisplatin (100 mg/m2 day 1 of a 28-day cycle) and vinorelbine (25 mg/m2 weekly). Patients were predominantly male (83%), had epithelioid histology (76%), had good performance status (95% PS 0-1), and were of advanced stage (82% stage III or IV). There were 15 partial responses and 1 complete response (RR 28%), with a median survival of 11.6 months (range 0.5 – 41.7+ months). However, 47% of patients developed leukocytopenia of grade 3 or greater, and 14% developed nausea of grade 3 or greater. There were no toxic deaths.
A second study from Denmark treated chemo-naïve MPM patients with vinorelbine plus carboplatin (AUC=5). The 27 patients who were accrued from 2005 – 2007 were predominantly male (89%), had epithelioid subtype (67%), had advanced stage (89% Stage III or IV), and had good performance status (78% PS 0-1). There have been five partial responses (RR 19%); median survival has not yet been reached but exceeds nine months. There have been seven cases of febrile neutropenia (25%) but no toxic deaths.
Targeted Therapies
In light of advances with targeted therapies in other tumor types, investigators have begun to explore the use of angiogenesis inhibitors and other targeted therapies in MPM. Unfortunately, recent results have not proved encouraging. In a randomized, multi-center Phase II trial of gemcitabine/cisplatin (GC) plus bevacizumab (B) or placebo, chemo-naïve patients were randomized to receive either GC plus placebo x 6 cycles or GC plus bevacizumab x 6 cycles followed by bevacizumab maintenance.[8] Patients were stratified by performance status and tumor histology (epithelioid vs. other). The results were presented at the 2007 ASCO Meeting and showed that the addition of bevacizumab was not associated with any significant improvement in median progression-free survival (6.9 months for GCB vs 6.0 months for GC, p = 0.88) or median overall survival (15.6 months for GCB vs 14.7 mo for GC, p = 0.91).
There has been only one published study dedicated exclusively to the second-line treatment of mesothelioma,[9] and there are currently no agents approved by the United States Food and Drug Administration in this setting. In attempt to fill this treatment void, several targeted agents have been studied for the second-line treatment of mesothelioma.
In a single-arm, multi-center Phase II study presented at the 12th World Conference on Lung Cancer, the use of bevacizumab plus erlotinib was explored in patients with unresectable mesothelioma who had previously received one prior chemotherapy regimen.[10] Unfortunately, in this clinical trial, there were no clinical responses, though there were a few patients with prolonged stable disease (up to 21 months). Median survival was eight months, and the one-year survival rate was 25%.
In another single-arm, multi-center Phase II study, patients who were either treatment naïve or had received prior chemotherapy were treated with the multi-targeted tyrosine kinase inhibitor sorafenib.[11] Among 51 enrolled patients, there were two partial responses, below the level required to meet the primary statistical response rate endpoint. Median failure-free survival was 3.7 months, and the median overall survival was 10.7 months. Median survival was better in the previously treated patients (14.7 months) compared with the chemo-naïve patients (4.9 months), though this was likely due to patient selection.
Summary
The management of malignant pleural mesothelioma continues to present difficult challenges for patients and their treating physicians. While there have been a number of long-term survivors in case series of multimodality therapy, it is not completely clear that this is truly attributable to the aggressive management rather than to more indolent disease. There have not yet been any randomized trials comparing surgery/multimodality therapy to chemotherapy alone. Moreover, if one considers the eligibility criteria (good performance status, no metastatic disease) for the Krug trial (above), the 16.6 month median survival may not represent a marked improvement over the 12.1 month median survival for cisplatin plus pemetrexed in patients with unresectable disease in the EMPHACIS trial. Until randomized trials can more clearly document an attributable benefit to multimodality therapy over chemotherapy alone, physicians need to proceed cautiously when recommended multimodality therapy in mesothelioma and improve methods for optimum patient selection for this treatment strategy.
The combination of cisplatin plus pemetrexed remains the systemic treatment of choice for previously untreated patients with mesothelioma. For those patients who cannot receive cisplatin, the substitution of carboplatin appears to be associated with roughly equivalent efficacy. For those patients who are deemed unfit for a combination regimen, pemetrexed monotherapy remains a reasonable option. However, in the absence of randomized data comparing monotherapy with a combination regimen, the use of pemetrexed plus a platinum agent remains the treatment of choice for those patients who are fit enough to tolerate it.
Systemic options beyond cisplatin plus pemetrexed remain unclear. The addition of bevacizumab to combination therapy with cisplatin and gemcitabine was not associated with any clinical benefit. Moreover, neither sorafenib nor the combination of erlotinib plus bevacizumab showed sufficient clinical benefit to warrant additional investigation in mesothelioma at this time. Trials with other targeted agents (vorinostat, bortezomib) are underway and may prove clinically useful in the care of patients with mesothelioma.By CancerConsultants.com
To date, treatment options have been limited. A small minority of mesothelioma patients may be appropriate for surgical intervention and multimodality therapy. For those patients with unresectable disease, systemic treatment with chemotherapy has achieved some success. Recent efforts have focused on exploring the role of multimodality therapy, improving patient selection for this aggressive strategy, and investigating new agents and new combinations of systemic therapies in MPM. Here we review recent data presented at the 2007 ASCO Meeting (Chicago, IL, June 2007) and at the 12th World Conference on Lung Cancer (Seoul, South Korea, September 2007).
Role of Surgery
The role of surgery in the management of MPM remains unclear. As yet, there have been no published randomized results comparing surgery to nonoperative management with conventional chemotherapy. However, among the case series that exist, there have been some encouraging preliminary results. In a case series published by Sugarbaker et al., there was a group of 31 patients who had epithelioid histology, clear resection margins, and no extrapleural nodes.[2] For this specific group, median survival was 51 months. These results have encouraged investigators at a number of centers to attempt to refine both the optimum treatment regimen and the selection of appropriate patients.
At the ASCO 2007 Meeting in Chicago, IL, Krug et al. presented results of a multi-center Phase II feasibility study of trimodality therapy.[3] Eligible patients had T1-3, N0-2, M0 malignant pleural mesothelioma, demonstrated good performance status (ECOG PS 0-1), were treatment-naïve, and had a post-operative FEV1 > 35%. Planned therapy included four cycles of cisplatin and pemetrexed. Following chemotherapy, non-progressing patients underwent extrapleural pneumonectomy followed by hemithoracic radiation to a total of 54 Gy. The 75 patients enrolled in the trial were predominantly male (70%) and most had epithelioid histology (80%). A total of 87% completed the planned four cycles of chemotherapy. Fifty-six patients (75%) eventually proceeded to extrapleural pneumonectomy (EPP), with 42 patients (56%) subsequently receiving radiation. Median time to progression for the entire group was 13.1 months, with a median overall survival of 16.6 months.
More recently, at the 12th World Conference on Lung Cancer in Seoul, South Korea, Smith et al. presented the results of a retrospective analysis of MPM patients at the Ottawa Hospital Regional Cancer Center.[4] A total of 147 MPM patients were identified. Multivariate analysis showed higher tumor stage, weight loss, poorer performance status, and an elevated platelet count to be independently associated with poor prognosis. In addition, the authors performed a case control analysis comparing MPM patients who underwent extrapleural pneumonectomy (n=15) with matched controls who did not undergo the radical surgery. Patients undergoing EPP had a median overall survival of 25.4 months (95% CI 12.2 – 43.6), with the result approaching but not reaching statistical significance compared with matched controls (p=0.007).
Systemic Therapy
With the publication of the EMPHACIS trial in 2003, combination treatment with cisplatin plus pemetrexed became the standard first-line therapy for patients with MPM.[5] In that study, patients were randomized to receive cisplatin alone vs. cisplatin plus pemetrexed. Median time to progression favored the combination therapy arm (5.7 months vs. 3.9 months, p=0.001); median overall survival also showed a benefit for patients treated with the two-drug regimen (12.1 months vs. 9.3 months, p = 0.02).
Pemetrexed and pemetrexed-based combinations
In the last six months, investigators have presented several analyses from the pemetrexed International Expanded Access Program (EAP). At the 2007 ASCO Meeting, Santoro et al. presented a comparison of pemetrexed plus cisplatin (P+Cis) vs. pemetrexed plus carboplatin (P + Cb).[6] In this retrospective, non-randomized comparison, the two arms demonstrated similar response rates (26% for P+Cis, 22% for P+Cb) and one-year survival rates (63% and 64%, respectively). Median survival for each group could not be estimated due to the high number of censored patients.
More recently, the same authors presented results of a 3-arm, non-randomized, open-label study of pemetrexed alone (P), pemetrexed plus cisplatin (P+Cis), and pemetrexed plus carboplatin (P+Cb) in chemo-naïve patients who were treated as part of the EAP.[7] Not surprisingly, the pemetrexed arm of this nonrandomized study contained a greater proportion of patients with poorer performance status. While pemetrexed monotherapy was associated with a lower treatment response rate, all three arms showed similar one-year survival rates and median time to disease progression.
Vinorelbine plus a platinum agent
Investigators from Denmark have explored the use of vinorelbine, rather than pemetrexed, in combination with a platinum agent. Dr. Sorensen et al. recently presented the results of two such nonrandomized Phase II studies at the 12th World Conference on Lung Cancer. The first, conducted from 2003 – 2006, treated 57 MPM patients with cisplatin (100 mg/m2 day 1 of a 28-day cycle) and vinorelbine (25 mg/m2 weekly). Patients were predominantly male (83%), had epithelioid histology (76%), had good performance status (95% PS 0-1), and were of advanced stage (82% stage III or IV). There were 15 partial responses and 1 complete response (RR 28%), with a median survival of 11.6 months (range 0.5 – 41.7+ months). However, 47% of patients developed leukocytopenia of grade 3 or greater, and 14% developed nausea of grade 3 or greater. There were no toxic deaths.
A second study from Denmark treated chemo-naïve MPM patients with vinorelbine plus carboplatin (AUC=5). The 27 patients who were accrued from 2005 – 2007 were predominantly male (89%), had epithelioid subtype (67%), had advanced stage (89% Stage III or IV), and had good performance status (78% PS 0-1). There have been five partial responses (RR 19%); median survival has not yet been reached but exceeds nine months. There have been seven cases of febrile neutropenia (25%) but no toxic deaths.
Targeted Therapies
In light of advances with targeted therapies in other tumor types, investigators have begun to explore the use of angiogenesis inhibitors and other targeted therapies in MPM. Unfortunately, recent results have not proved encouraging. In a randomized, multi-center Phase II trial of gemcitabine/cisplatin (GC) plus bevacizumab (B) or placebo, chemo-naïve patients were randomized to receive either GC plus placebo x 6 cycles or GC plus bevacizumab x 6 cycles followed by bevacizumab maintenance.[8] Patients were stratified by performance status and tumor histology (epithelioid vs. other). The results were presented at the 2007 ASCO Meeting and showed that the addition of bevacizumab was not associated with any significant improvement in median progression-free survival (6.9 months for GCB vs 6.0 months for GC, p = 0.88) or median overall survival (15.6 months for GCB vs 14.7 mo for GC, p = 0.91).
There has been only one published study dedicated exclusively to the second-line treatment of mesothelioma,[9] and there are currently no agents approved by the United States Food and Drug Administration in this setting. In attempt to fill this treatment void, several targeted agents have been studied for the second-line treatment of mesothelioma.
In a single-arm, multi-center Phase II study presented at the 12th World Conference on Lung Cancer, the use of bevacizumab plus erlotinib was explored in patients with unresectable mesothelioma who had previously received one prior chemotherapy regimen.[10] Unfortunately, in this clinical trial, there were no clinical responses, though there were a few patients with prolonged stable disease (up to 21 months). Median survival was eight months, and the one-year survival rate was 25%.
In another single-arm, multi-center Phase II study, patients who were either treatment naïve or had received prior chemotherapy were treated with the multi-targeted tyrosine kinase inhibitor sorafenib.[11] Among 51 enrolled patients, there were two partial responses, below the level required to meet the primary statistical response rate endpoint. Median failure-free survival was 3.7 months, and the median overall survival was 10.7 months. Median survival was better in the previously treated patients (14.7 months) compared with the chemo-naïve patients (4.9 months), though this was likely due to patient selection.
Summary
The management of malignant pleural mesothelioma continues to present difficult challenges for patients and their treating physicians. While there have been a number of long-term survivors in case series of multimodality therapy, it is not completely clear that this is truly attributable to the aggressive management rather than to more indolent disease. There have not yet been any randomized trials comparing surgery/multimodality therapy to chemotherapy alone. Moreover, if one considers the eligibility criteria (good performance status, no metastatic disease) for the Krug trial (above), the 16.6 month median survival may not represent a marked improvement over the 12.1 month median survival for cisplatin plus pemetrexed in patients with unresectable disease in the EMPHACIS trial. Until randomized trials can more clearly document an attributable benefit to multimodality therapy over chemotherapy alone, physicians need to proceed cautiously when recommended multimodality therapy in mesothelioma and improve methods for optimum patient selection for this treatment strategy.
The combination of cisplatin plus pemetrexed remains the systemic treatment of choice for previously untreated patients with mesothelioma. For those patients who cannot receive cisplatin, the substitution of carboplatin appears to be associated with roughly equivalent efficacy. For those patients who are deemed unfit for a combination regimen, pemetrexed monotherapy remains a reasonable option. However, in the absence of randomized data comparing monotherapy with a combination regimen, the use of pemetrexed plus a platinum agent remains the treatment of choice for those patients who are fit enough to tolerate it.
Systemic options beyond cisplatin plus pemetrexed remain unclear. The addition of bevacizumab to combination therapy with cisplatin and gemcitabine was not associated with any clinical benefit. Moreover, neither sorafenib nor the combination of erlotinib plus bevacizumab showed sufficient clinical benefit to warrant additional investigation in mesothelioma at this time. Trials with other targeted agents (vorinostat, bortezomib) are underway and may prove clinically useful in the care of patients with mesothelioma.By CancerConsultants.com
Thursday, August 14, 2008
Increased risk
Asbestos has been mined and used commercially since the late 1800s. Its use greatly increased during World War II. Since the early 1940s, millions of American workers have been exposed to asbestos dust. Initially, the risks associated with asbestos exposure were not known. However, an increased risk of developing mesothelioma was later found among shipyard workers, people who work in asbestos mines and mills, producers of asbestos products, workers in the heating and construction industries, and other tradespeople. Today, the U.S. Occupational Safety and Health Administration (OSHA) sets limits for acceptable levels of asbestos exposure in the workplace. People who work with asbestos wear personal protective equipment to lower their risk of exposure.
The risk of asbestos-related disease increases with heavier exposure to asbestos and longer exposure time. However, some individuals with only brief exposures have developed mesothelioma. On the other hand, not all workers who are heavily exposed develop asbestos-related diseases.
There is some evidence that family members and others living with asbestos workers have an increased risk of developing mesothelioma, and possibly other asbestos-related diseases. This risk may be the result of exposure to asbestos dust brought home on the clothing and hair of asbestos workers. To reduce the chance of exposing family members to asbestos fibers, asbestos workers are usually required to shower and change their clothing before leaving the workplace.
The risk of asbestos-related disease increases with heavier exposure to asbestos and longer exposure time. However, some individuals with only brief exposures have developed mesothelioma. On the other hand, not all workers who are heavily exposed develop asbestos-related diseases.
There is some evidence that family members and others living with asbestos workers have an increased risk of developing mesothelioma, and possibly other asbestos-related diseases. This risk may be the result of exposure to asbestos dust brought home on the clothing and hair of asbestos workers. To reduce the chance of exposing family members to asbestos fibers, asbestos workers are usually required to shower and change their clothing before leaving the workplace.
Your Legal Rights
Mesothelioma and Your Legal Rights
Mesothelioma Source is dedicated to providing those diagnosed with mesothelioma and their families every possible resource. We understand that coping with mesothelioma is a difficult process, and you may or may not choose to pursue a lawsuit. However, if you are interested in your legal options, this section provides information on the litigation process as well as how to select an attorney.
The Typical Recovery Process
This section covers the key parts of a typical asbestos lawsuit. Please note that every lawsuit is different, and this list covers the major elements that can be reasonably expected.
1. Preparation
Before the actual lawsuit lawsuit is filed, you and the lawyer you have chosen will sign an attorney-client contract. In addition, the attorney will request that you sign medical, employment, and social security releases. This information is necessary for the attorneys you're working with to gather information and evidence to assist them in the lawsuit.
In addition, your attorney will ask you a number of important questions about where you have worked and what you remember about your asbestos exposure. This should include the number of years worked, your acquaintances, and the names of any asbestos products you remember working with.
2. Lawsuit Filing
This stage of the lawsuit occurs after your attorney has gathered as much information as possible on the details of your asbestos exposure. A formal document, or �complaint' is filed that informs the defendants, typically the companies responsible for your exposure, of the details of your claim. Typically, the defendant(s) will then reply to your claim with either a denial of responsibility or a motion to dismiss the lawsuit. These motions to dismiss are often a tactic used by the asbestos companies to stall, hoping that you won't live long enough to see the trial.
3. Discovery
This phase of the process occurs after any motions to dismiss are denied and the defendant(s) reply to the claim. The defendant will typically submit a number of written questions in the form of interrogatories, which you will be required to answer under oath. In addition, they will seek to obtain past medical records and find other possible causes, such as smoking. Another common defense is the claim that you have known about your asbestos-related disease longer than originally claimed, which exceeds the statute of limitations.
4. The Trial - Steps
1. Jury Selection
2. Preliminary Jury Instructions
3. Plaintiff Opening Statement
4. Defense Opening Statement
5. Plaintiff Evidence & Witnesses
6. Plaintiff Rests Case
7. Defense Motions to Dismiss Lawsuit
8. Defense Evidence & Witnesses
9. Defense Rests Case
10. Plaintiff Evidence & Witnesses to Rebutt Defense
11. Jury Instructions
12. Plaintiff Closing Statement
13. Defense Closing Statement
14. Plaintiff's Rebuttal Closing
15. Jury Deliberations
16. Verdict
5. Appeals
Appeals can occur if the jury awards compensation to the plaintiff. However, if the defense appeals the verdict, they must �post bond' in the amount of the award that was decided by the jury.
Mesothelioma Source is dedicated to providing those diagnosed with mesothelioma and their families every possible resource. We understand that coping with mesothelioma is a difficult process, and you may or may not choose to pursue a lawsuit. However, if you are interested in your legal options, this section provides information on the litigation process as well as how to select an attorney.
The Typical Recovery Process
This section covers the key parts of a typical asbestos lawsuit. Please note that every lawsuit is different, and this list covers the major elements that can be reasonably expected.
1. Preparation
Before the actual lawsuit lawsuit is filed, you and the lawyer you have chosen will sign an attorney-client contract. In addition, the attorney will request that you sign medical, employment, and social security releases. This information is necessary for the attorneys you're working with to gather information and evidence to assist them in the lawsuit.
In addition, your attorney will ask you a number of important questions about where you have worked and what you remember about your asbestos exposure. This should include the number of years worked, your acquaintances, and the names of any asbestos products you remember working with.
2. Lawsuit Filing
This stage of the lawsuit occurs after your attorney has gathered as much information as possible on the details of your asbestos exposure. A formal document, or �complaint' is filed that informs the defendants, typically the companies responsible for your exposure, of the details of your claim. Typically, the defendant(s) will then reply to your claim with either a denial of responsibility or a motion to dismiss the lawsuit. These motions to dismiss are often a tactic used by the asbestos companies to stall, hoping that you won't live long enough to see the trial.
3. Discovery
This phase of the process occurs after any motions to dismiss are denied and the defendant(s) reply to the claim. The defendant will typically submit a number of written questions in the form of interrogatories, which you will be required to answer under oath. In addition, they will seek to obtain past medical records and find other possible causes, such as smoking. Another common defense is the claim that you have known about your asbestos-related disease longer than originally claimed, which exceeds the statute of limitations.
4. The Trial - Steps
1. Jury Selection
2. Preliminary Jury Instructions
3. Plaintiff Opening Statement
4. Defense Opening Statement
5. Plaintiff Evidence & Witnesses
6. Plaintiff Rests Case
7. Defense Motions to Dismiss Lawsuit
8. Defense Evidence & Witnesses
9. Defense Rests Case
10. Plaintiff Evidence & Witnesses to Rebutt Defense
11. Jury Instructions
12. Plaintiff Closing Statement
13. Defense Closing Statement
14. Plaintiff's Rebuttal Closing
15. Jury Deliberations
16. Verdict
5. Appeals
Appeals can occur if the jury awards compensation to the plaintiff. However, if the defense appeals the verdict, they must �post bond' in the amount of the award that was decided by the jury.
Time Restrictions
Time Restrictions for Asbestos Disease and Mesothelioma Litigation
The diagnosis of an asbestos disease starts the running of a very strict time period within which claims must be asserted, or they may be lost or barred forever. This is called the statute of limitations, and it differs slightly from state to state.
Considering the statute of limitations, anyone diagnosed with an asbestos disease should seek legal advice at once. Because individual circumstances are so important, you should not rely upon this overview in place of in-person legal advice from an attorney. Anyone wishing to protect their legal rights should not delay in seeking legal counsel.
The asbestos lawyers at Wilentz, Goldman, and Spitzer are members of one of the largest firms in the United States representing asbestos victims and their families.
Those who have contracted mesothelioma due to asbestos exposure deserve to have the best and most experienced asbestos lawyer. Clients at Wilentz always have access to their asbestos lawyer to discuss any matter relating to their case. Because our asbestos lawyers are focused on asbestos and mesothelioma litigation all of the time, we can provide the personalized service and expertise that each case deserves.
At Wilentz, Goldman, and Spitzer, we have the resources available for each asbestos lawyer to try your case at the highest level.
The diagnosis of an asbestos disease starts the running of a very strict time period within which claims must be asserted, or they may be lost or barred forever. This is called the statute of limitations, and it differs slightly from state to state.
Considering the statute of limitations, anyone diagnosed with an asbestos disease should seek legal advice at once. Because individual circumstances are so important, you should not rely upon this overview in place of in-person legal advice from an attorney. Anyone wishing to protect their legal rights should not delay in seeking legal counsel.
The asbestos lawyers at Wilentz, Goldman, and Spitzer are members of one of the largest firms in the United States representing asbestos victims and their families.
Those who have contracted mesothelioma due to asbestos exposure deserve to have the best and most experienced asbestos lawyer. Clients at Wilentz always have access to their asbestos lawyer to discuss any matter relating to their case. Because our asbestos lawyers are focused on asbestos and mesothelioma litigation all of the time, we can provide the personalized service and expertise that each case deserves.
At Wilentz, Goldman, and Spitzer, we have the resources available for each asbestos lawyer to try your case at the highest level.
Choosing Your Lawyer / Law Firm
Choose The Law Firm
There are two types of law firms that handle mesothelioma lawsuits: larger, more traditional firms that handle many asbestos-related disease cases, many of which are non-cancerous, and smaller, newer law firms that deal exclusively with mesothelioma cases. Firms that take on a wide variety of asbestos-related cases often times have pre-established settlement agreements with asbestos manufacturers and, in general, spend less time on individual cases as they are more concerned with larger, group settlements.
Other advantages of mesothelioma exclusive firms:
* Selective when choosing which cases to take
* Give plaintiffs individual attention
* Experienced in trial and settlement arrangements for single plaintiff cases
* Spend more time on individual cases
Based on your personal needs and desires, you should choose which type of firm is right for your case. In either instance, you should look for a firm with experience and knowledge.
Some things to look for in a law firm:
* Experienced in claims process
* Proven track record
* Strong network of counsel
* Familiarity with cover-ups and incriminating asbestos company documents
There are two types of law firms that handle mesothelioma lawsuits: larger, more traditional firms that handle many asbestos-related disease cases, many of which are non-cancerous, and smaller, newer law firms that deal exclusively with mesothelioma cases. Firms that take on a wide variety of asbestos-related cases often times have pre-established settlement agreements with asbestos manufacturers and, in general, spend less time on individual cases as they are more concerned with larger, group settlements.
Other advantages of mesothelioma exclusive firms:
* Selective when choosing which cases to take
* Give plaintiffs individual attention
* Experienced in trial and settlement arrangements for single plaintiff cases
* Spend more time on individual cases
Based on your personal needs and desires, you should choose which type of firm is right for your case. In either instance, you should look for a firm with experience and knowledge.
Some things to look for in a law firm:
* Experienced in claims process
* Proven track record
* Strong network of counsel
* Familiarity with cover-ups and incriminating asbestos company documents
Expectation
Settlements in these types of cases vary greatly based on type of exposure. Because of this, it is difficult to give an average settlement. However, many claimants receive compensation to the tune of 6 to 7 figures.
After a settlement is agreed to, it could take from six months to a year or more before the plaintiff receives any money because asbestos companies have to submit claims to their insurers who are often handling thousands of settlements at a time.
When settlements are being arranged, your lawyer could be dealing with a number of different companies at one time, and will therefore be in constant negotiation. Many times these settlements are agreed to just hours before trial, and plaintiffs may feel left out and confused as they are receiving little attention fro their attorney. Though this is sometimes inevitable, you should feel assured that your lawyer is working to provide adequate compensation.
After a settlement is agreed to, it could take from six months to a year or more before the plaintiff receives any money because asbestos companies have to submit claims to their insurers who are often handling thousands of settlements at a time.
When settlements are being arranged, your lawyer could be dealing with a number of different companies at one time, and will therefore be in constant negotiation. Many times these settlements are agreed to just hours before trial, and plaintiffs may feel left out and confused as they are receiving little attention fro their attorney. Though this is sometimes inevitable, you should feel assured that your lawyer is working to provide adequate compensation.
Questions To Ask Your Lawyer
Because many states have a statute of limitations for filing these types of lawsuits that begins at original diagnosis, it is important to contact a lawyer quickly if you are considering taking legal action. Not all lawyers and law firms have the same experience with specific cases, so explaining your particular case will get you the help you need. Mesothelioma patients can file claims through personal disability or life insurance policies, Social Security, against their former employer, and against asbestos manufacturers. The largest compensations are usually recovered from claims against the asbestos industry.
Any given law firm will have specialized experience in one type of case and not necessarily the others. Ask your lawyer his/her experience with mesothelioma cases and look for lawyers experienced in handling cases like yours. If your asbestos exposure spans more than one state or county, ask which jurisdiction your case will be tried in, as average compensation varies based on region. Some larger firms may have settlement agreements already established with asbestos companies and may not be able to take your case to court individually. You should find out early if your case will be treated separately or as a class-action suit.
Any given law firm will have specialized experience in one type of case and not necessarily the others. Ask your lawyer his/her experience with mesothelioma cases and look for lawyers experienced in handling cases like yours. If your asbestos exposure spans more than one state or county, ask which jurisdiction your case will be tried in, as average compensation varies based on region. Some larger firms may have settlement agreements already established with asbestos companies and may not be able to take your case to court individually. You should find out early if your case will be treated separately or as a class-action suit.
Mesothelioma Legal Rights
Taking Legal Action
If you or a family member have been diagnosed with mesothelioma, you could be entitled to monetary compensation form asbestos companies, insurance companies and past employers. Asbestos exposure is the only known cause of mesothelioma, a tumor infecting the lining around internal organs such as the lungs and abdomen. Since the 1920's, asbestos manufacturers were aware of health risks associated with asbestos exposure. From that time until the 1970's many of these companies conspired to cover up scientific findings linking asbestos to lung disease and cancer.
Aware of the risks, asbestos companies continued producing their products, exposing millions to the mineral that can prove lethal if airborne fibers are inhaled or swallowed. Since the late 1970's and early 80's individuals suffering from asbestos related diseases have filed many claims against producers of asbestos products. Monetary settlements are given to plaintiffs and their families to compensate for medical bills, which can average $200,000 annually for mesothelioma patients, and reduction of quality of life.
If you or a family member have been diagnosed with mesothelioma, you could be entitled to monetary compensation form asbestos companies, insurance companies and past employers. Asbestos exposure is the only known cause of mesothelioma, a tumor infecting the lining around internal organs such as the lungs and abdomen. Since the 1920's, asbestos manufacturers were aware of health risks associated with asbestos exposure. From that time until the 1970's many of these companies conspired to cover up scientific findings linking asbestos to lung disease and cancer.
Aware of the risks, asbestos companies continued producing their products, exposing millions to the mineral that can prove lethal if airborne fibers are inhaled or swallowed. Since the late 1970's and early 80's individuals suffering from asbestos related diseases have filed many claims against producers of asbestos products. Monetary settlements are given to plaintiffs and their families to compensate for medical bills, which can average $200,000 annually for mesothelioma patients, and reduction of quality of life.
Saturday, August 9, 2008
Mesothelioma Info
Mesothelioma Info
Information on mesothelioma, treatment centers, clinical trials, and specialists; asbestos, laws, litigation history, and legal assistance.
Mesothelioma Legal Information Center
Mesothelioma Information: Definition Mesothelioma is a rare form of cancer. In mesothelioma, malignant cells are found in the sac lining of the chest (the pleura) or the abdomen ...
Mesothelioma Information
MesoLink provides you with up to date information on the deadly disease Mesothelioma. We strive to provide the most complete overview of the disease, its diagnosis, treatment ...
MesoLink.org -- Your Link To Mesothelioma Information
Comprehensive information site on mesothelioma diagnosis, treatment, coping, asbestos disease and financial assistance.
Mesothelioma.com - The Authority on Mesothelioma and Asbestos Cancer
Mesothelioma health information. ... Find out why buying property in Spain is becoming a trend with cancer survivors. http://www.buyspain.co.uk as a good place to see just how good ...
Mesothelioma Health Information
Mesothelioma Information provides information on related cancer, medical treatment options for mesothelioma and legal rights for victims of mesothelioma. Discuss your lung cancer ...
Mesothelioma Information - The Asbestos Cancer Resource
Mesothelioma Information Resource Group provides mesothelioma information on treatments, current news, asbestos lung cancer, legal rights.
Mesothelioma Information Resource Group - providing mesothelioma ...
Union carbide and Dupoint have been sued in a lawsuit by a housewife- Frances Barras, Nederland. She claimed that she washed her Hubby�s clothes from 1957 to 1985, which resulted ...
Mesothelioma Information
Mesothelioma Information Centre; Medlineplus: Mesothelioma from MEDLINE, part of the United States National Library of Medicine; Worksafe, Western Australia, from Western Australia's ...
Mesothelioma - Wikipedia, the free encyclopedia
The Mesothelioma Directory providing information and the best mesothelioma sites to help you. ... The Mesothelioma Info Directory is dedicated to providing the most up to date, and ...
Information on mesothelioma, treatment centers, clinical trials, and specialists; asbestos, laws, litigation history, and legal assistance.
Mesothelioma Legal Information Center
Mesothelioma Information: Definition Mesothelioma is a rare form of cancer. In mesothelioma, malignant cells are found in the sac lining of the chest (the pleura) or the abdomen ...
Mesothelioma Information
MesoLink provides you with up to date information on the deadly disease Mesothelioma. We strive to provide the most complete overview of the disease, its diagnosis, treatment ...
MesoLink.org -- Your Link To Mesothelioma Information
Comprehensive information site on mesothelioma diagnosis, treatment, coping, asbestos disease and financial assistance.
Mesothelioma.com - The Authority on Mesothelioma and Asbestos Cancer
Mesothelioma health information. ... Find out why buying property in Spain is becoming a trend with cancer survivors. http://www.buyspain.co.uk as a good place to see just how good ...
Mesothelioma Health Information
Mesothelioma Information provides information on related cancer, medical treatment options for mesothelioma and legal rights for victims of mesothelioma. Discuss your lung cancer ...
Mesothelioma Information - The Asbestos Cancer Resource
Mesothelioma Information Resource Group provides mesothelioma information on treatments, current news, asbestos lung cancer, legal rights.
Mesothelioma Information Resource Group - providing mesothelioma ...
Union carbide and Dupoint have been sued in a lawsuit by a housewife- Frances Barras, Nederland. She claimed that she washed her Hubby�s clothes from 1957 to 1985, which resulted ...
Mesothelioma Information
Mesothelioma Information Centre; Medlineplus: Mesothelioma from MEDLINE, part of the United States National Library of Medicine; Worksafe, Western Australia, from Western Australia's ...
Mesothelioma - Wikipedia, the free encyclopedia
The Mesothelioma Directory providing information and the best mesothelioma sites to help you. ... The Mesothelioma Info Directory is dedicated to providing the most up to date, and ...
Overview of Mesothelioma of the Tunica Vaginalis
Mesothelioma of the tunica vaginalis is the rarest form of malignant mesothelioma. The authors of this article state their awareness of only 98 other cases. Different articles have reported slightly different numbers, but the basic truth of these statements refers to the extreme rarity of the disease. Asbestos exposure is the most commonly reported causative factor, but specific conclusions are very difficult with such a small population set to learn from. Histologically speaking, most cases of the disease are of the epitheloid subtype (60-75%), with the biphasic subtype making up the remainder of diagnoses. The authors state that “pure sarcomatous mesothelioma is exceedingly rare.” The average age of diagnosis is 60 years-old and because the disease specifically grows from the tunica vaginalis—the lining that surrounds the testes—it only affects men.
In most cases, the disease remains undiagnosed until the area is operated on or an autopsy reveals the presence of the malignancy after a patient has died. If a patient does present with a testicular issue, the disease is likely to be misdiagnosed for a number of more common conditions. This situation—as is the case with most forms of mesothelioma—means that the malignancy is likely to be in a less treatable state when a diagnosis is finally returned.
Overview of the Case
The authors describe the patient as a 60 year-old man with swelling on the left side of his scrotum. The man smoked for twenty years, but was not occupationally exposed to asbestos. Like all forms of mesothelioma, asbestos exposure is the main indication for this varient, so it is likely that the patient was simply not aware of his exposure to the mineral. Many diagnostic tests returned normal results, but sonographic testing revealed a number of troubling findings, including an enlarged left testicle and a large hydrocele in the left scrotum. A 1.5 x 1 x1.5-cm polypoid mass (polyp) demonstrating “increased vascularity” was discovered in the scrotal wall, and two similar masses were discovered in the tunica vaginalis.
The patient then received a left hydrocelectomy and scrotal exploration and had tissue removed for biopsy. The biopsy revealed mesothelioma of the tunica vaginalis, biphasic subtype. After a left radical orchitectomy and hemiscrotectomy, a 4-cm tumor attached to the tunica vaginalis was discovered. Immunohistochemical analysis conducted on the tumor confirmed the mesothelioma diagnosis.
Further testing revealed that the cancer had metastasized to the retroperitoneal lymph nodes. The patient then began chemotherapy. 21 months after initial diagnosis, PET indicated distant tissue infiltration and CT demonstrated significant metastases in the lungs and mediastinum. After this discovery, the patient was started on another course of chemotherapy.
Color Doppler Sonography
As we stated above, most cases of mesothelioma of the tunica vaginalis are not diagnosed until surgery or autopsy. Due to its rarity, most physicians will not have any experience with the disease and will certainly not be on the lookout for it. Regarding the case under discussion, the authors were able to identify the disease fairly early and were able to start treatment for it soon after discovery—which was almost certainly a factor in the patient’s survival 21 months after initial diagnosis. The authors state that imaging methodologies have traditionally been of limited use, but research into the sonographic representation of the tumor has begun to identify characteristics particular to it. Along with that research, the use of newer technologies in the analysis of tissue structures has also been important. For this particular case presentation, the authors used color Doppler sonography to identify areas of increased blood flow (hypervascularity) in the identified scrotal masses, which indicated the presence of a possible malignancy. Color Doppler sonogrography is an ultrasonic imaging technology that identifies blood flow and represents these varying rates using colors. Many scrotal masses are relatively benign conditions and do not demonstrate increased vascularity, so the use of an imaging technology that is sensitive to increased blood flow can help to differentiate the mesothelioma from other conditions. If a malignancy is suspected, fine needle aspiration or the removal of tissue—in addition or, or instead of, the excision of the affected testicle—can be attempted to definitively determine a diagnosis.
Conclusion
The authors conclude that color Doppler sonography may be an important new tool for the diagnosis of mesothelioma of the tunica vaginalis. Mesothelioma is a very aggressive tumor in all its forms, so early diagnosis and treatment is a key element in maximizing patient survival time. Because the disease is so rare, it is unlikely that studies will be attempted to precisely quantify this technology’s diagnostic value, so case reports such as these remain the best way to learn more about mesothelioma of the tunica vaginalis.
Cancer Survivors Find Support
The Wall Street Journal has published an article on support groups and other wellness programs for cancer survivors. As more and more people are surviving cancer, there is concern that doctors and other medical professionals are not doing enough to support the psychological health of the survivors. Study after study has shown that support groups offer survivors the psychological support they need to return to their everyday lives. Because of these findings, cancer-advocacy groups, major cancer centers, insurance companies and oncology medical societies are all exploring expanded programs to better meet the total needs of patients and survivors. The Institute of Medicine (IOM) has developed a series of models and screening mechanisms to enable health-care providers to better understand the psychological states of their patients. Because oncologists are rarely trained in the non-medical aspects of treatment, the IOM hopes its models will enable a more open dialogue between a doctor and his or her patient.
In all cases, it's clear that treating cancer isn't just treating the biological aspects of the disease. Treating patients means being attuned to their total needs. While the medical aspects of treatment are certainly the most important, doctors and care providers should also be motivated to help patients find the social and psychological support they crave as well.
In all cases, it's clear that treating cancer isn't just treating the biological aspects of the disease. Treating patients means being attuned to their total needs. While the medical aspects of treatment are certainly the most important, doctors and care providers should also be motivated to help patients find the social and psychological support they crave as well.
Mesothelioma Science
Malignant mesothelioma typically presents as a diffuse disorder, with a large number of tumors spread throughout an entire tissue area. Localized presentations, where histological analysis clearly establishes a diagnosis of malignant mesothelioma but whose behavior is characterized by a single mass without evidence of diffuse spread or distant metastases, are exceedingly rare tumors. In fact, the literature only describes forty-five such cases. Due to its rarity, little is known about this form of mesothelioma.
The first descriptions of localized mesothelioma appeared in the early 1990s and described a cohort of six patients. After this initial report, additional studies and anecdotal reports began to appear, but these were few and relatively far between. In 2005, researchers presented the largest current analysis of localized mesothelioma, which described twenty-three new cases and summarized the literature on the previously reported cases. Of the forty-five known cases, thirty-nine presented with a localized pleural tumor. Two presented with a localized peritoneal tumor and two others presented with a localized pericardial tumor.
With so few cases to study, the Japanese researchers were not able to make definitive conclusions on the etiology and underlying development of the disease, but they were able to use their case report to make some general statements on localized mesothelioma.
Case Study
The researchers describe a 54 year-old man suffering from chest discomfort and heart palpitations. An x-ray revealed an abnormal shadow in the area of his chest associated with the discomfort and CT showed pleural thickening. He was given a diagnosis of a benign pleural tumor and then told to return in a few months for a follow-up. After six months the tumor had grown only slightly, but a CT taken fourteen months later showed significant increase in tumor size and some evidence of chest-wall invasion. A needle biopsy returned results positive for malignant mesothelioma, but physical examination revealed a localized neoplasm without tissue diffusion or distant metastases.
Surgery was then scheduled to remove the growing mass. Doctors identified and removed a single tumor approximately 5cm in size. The tumor had invaded the middle lobe of the lung, but no farther. Histopathology of the tumor itself confirmed malignant mesothelioma, biphasic type. There was neither diffuse spread of the tumor throughout the pleura, nor were any pleural effusions discovered—a clear indication of the behavioral differences between localized and diffuse mesothelioma.
The surgery was declared a complete success when all surgical margins were negative for malignant tissue. The doctors report the man’s prognosis as excellent. Two years after his surgery he is free of the cancer and it shows no signs of returning.
Conclusion
Localized malignant mesothelioma is a very rare subclass of mesothelioma. Normally characterized by gross tissue involvement and general resistance to treatment, malignant mesothelioma remains among the most difficult of all cancers to manage effectively. Prognosis is generally poor and life expectancy is often reduced.
The localized variant of the disease shows none of these characteristics. Histologically the disease is mesothelioma, but its behavior is quite different. Instead of diffuse spread, this version of the disease presents as a single mass with clear boundaries and a seemingly non-aggressive development pattern. As in the case of the man covered here, the tumor appears to be rather slow-growing (there was a period of 16 months between initial x-ray and surgery) and quite amenable to treatment. While a few of the cases in the literature report a metastatic potential and some recurrence after surgery, most do not, so the prognosis for a person with localized mesothelioma seems to much better than a person with the more commonly-seen diffuse disease.
The first descriptions of localized mesothelioma appeared in the early 1990s and described a cohort of six patients. After this initial report, additional studies and anecdotal reports began to appear, but these were few and relatively far between. In 2005, researchers presented the largest current analysis of localized mesothelioma, which described twenty-three new cases and summarized the literature on the previously reported cases. Of the forty-five known cases, thirty-nine presented with a localized pleural tumor. Two presented with a localized peritoneal tumor and two others presented with a localized pericardial tumor.
With so few cases to study, the Japanese researchers were not able to make definitive conclusions on the etiology and underlying development of the disease, but they were able to use their case report to make some general statements on localized mesothelioma.
Case Study
The researchers describe a 54 year-old man suffering from chest discomfort and heart palpitations. An x-ray revealed an abnormal shadow in the area of his chest associated with the discomfort and CT showed pleural thickening. He was given a diagnosis of a benign pleural tumor and then told to return in a few months for a follow-up. After six months the tumor had grown only slightly, but a CT taken fourteen months later showed significant increase in tumor size and some evidence of chest-wall invasion. A needle biopsy returned results positive for malignant mesothelioma, but physical examination revealed a localized neoplasm without tissue diffusion or distant metastases.
Surgery was then scheduled to remove the growing mass. Doctors identified and removed a single tumor approximately 5cm in size. The tumor had invaded the middle lobe of the lung, but no farther. Histopathology of the tumor itself confirmed malignant mesothelioma, biphasic type. There was neither diffuse spread of the tumor throughout the pleura, nor were any pleural effusions discovered—a clear indication of the behavioral differences between localized and diffuse mesothelioma.
The surgery was declared a complete success when all surgical margins were negative for malignant tissue. The doctors report the man’s prognosis as excellent. Two years after his surgery he is free of the cancer and it shows no signs of returning.
Conclusion
Localized malignant mesothelioma is a very rare subclass of mesothelioma. Normally characterized by gross tissue involvement and general resistance to treatment, malignant mesothelioma remains among the most difficult of all cancers to manage effectively. Prognosis is generally poor and life expectancy is often reduced.
The localized variant of the disease shows none of these characteristics. Histologically the disease is mesothelioma, but its behavior is quite different. Instead of diffuse spread, this version of the disease presents as a single mass with clear boundaries and a seemingly non-aggressive development pattern. As in the case of the man covered here, the tumor appears to be rather slow-growing (there was a period of 16 months between initial x-ray and surgery) and quite amenable to treatment. While a few of the cases in the literature report a metastatic potential and some recurrence after surgery, most do not, so the prognosis for a person with localized mesothelioma seems to much better than a person with the more commonly-seen diffuse disease.
Saturday, August 2, 2008
ASBESTOS IN DRINKING WATER
Asbestos is a remarkable material. It is a mineral composed of elements much like those of sand, but it comes in the form of long, thin, submicroscopic fibers. Materials made from asbestos are light, fireproof, flexible, and tough. During the decades of the 50’s to 70’s, when it was referred to as “the magic mineral” (Roggli and Coin, 2004), it was used in building materials, roofing tiles, pipe insulation, brake liners, fireproof clothing and mitts, and sometimes appeared in the kitchen as a heatproof stovepad. It was also used in asbestos/concrete pipe for water transport. In this case, it was valued not for its fireproofing ability, but because the fibers helped bind the concrete. At 25% asbestos, 75% concrete (OSHRC Docket No. 01-0261), asbestos made the pipes lighter and easier to install. This pipe was intended for such purposes as irrigation, but because it was plentiful and cheap, asbestos/concrete or AC pipe, also known by its trade name, Transite, was used to transport drinking water in municipal water systems across the United States and Canada. There are an estimated 200,000 miles or more of asbestos/concrete pipes in US water systems today (Olson, 1974, cited in Millette et al., 1980).
In the 1970’s, another property of asbestos became too obvious to ignore. Exposure to asbestos can cause death.
Workers exposed to asbestos in their jobs became ill and died of particular diseases. Over time, it was discovered that exposure to airborne asbestos fibers could lead, decades later, to asbestosis, lung cancer, and mesothelioma, a cancer of the lining of the body cavities. Mesothelioma is a hallmark of asbestos exposure; it is a distinctive and, even now, extremely rare form of cancer. About 15-20 cases occur per million men each year in North America, and far fewer women develop the disease. Almost every person who has ever developed mesothelioma has had occupational exposure to asbestos at least 15 years prior, and sometimes as long as 70 years before. The peak in incidence occurs 30 to 40 years after exposure (Sporn and Roggli, 2004).
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Other kinds of cancer also showed up decades after asbestos exposure. By the early 80’s, five studies had shown that cancers of the stomach and other parts of the gastrointestinal (GI) system occurred at higher rates in asbestos workers. The risk ranged from somewhat higher than non-exposed control workers (1.32 in London factory workers) to almost 3 times the usual risk in New York and New Jersey insulation workers (Safe Drinking Water Committee, 1983). It became clear that at least some GI cancers are likely related to asbestos exposure (Rolston and Oury, 2004).
What was not clear was whether inhaled asbestos fibers had migrated through the body from the lungs to cause these cancers, or whether fibers from the lungs, coughed up and then swallowed, might have entered the stomach and other digestive organs more directly, from ingestion.
This question was important then, and is still important now, because, as noted above, hundreds of thousands of miles of asbestos/concrete pipe are used to transport the drinking water for many Americans. This pipe is known to shed asbestos fibers (Safe Drinking Water Committee, 1983). Even at relatively low exposures, if swallowed asbestos can cause cancer, exposing millions of people to asbestos in their drinking water could be considered dangerous (CCERP, 1987).
This report reviews the scientific literature relating to the possible carcinogenicity (cancer-causing ability) of asbestos taken by mouth, as in drinking water. Because reviews of this literature in the 1980s had a substantial impact on public policy regarding asbestos in drinking water, I summarize that literature first. I then review literature to 2005 and discuss the impact of the more recent findings on our current knowledge concerning the carcinogenicity of asbestos in drinking water.
STUDIES ON INGESTED ASBESTOS AND CANCER THROUGH THE ‘80s
A number of scientific studies done in the 1970’s and 1980’s addressed the question of whether swallowed asbestos could cause cancer. Since it is unethical to deliberately expose people to suspected cancer-causing agents unless it is considered beneficial to them, the studies used animal models and “natural experiments” in which humans had been exposed to asbestos in their drinking water. The many approaches to this question in animal models included direct injection or surgical implantation of asbestos into the body followed by examination for tumors, testing of whether asbestos given by mouth could penetrate body tissues, and administration of asbestos in food or water followed by examination for tumors.
DIRECT INJECTION OF ASBESTOS: EFFECTS
Several studies established that direct injection or surgical implantation of asbestos into the body cavities of rats and hamsters produced tumors. Forty-one rats injected with asbestos into the lung cavity, for example, developed 5 mesotheliomas in the abdomen in addition to 20 mesotheliomas of the lining of the lung (pleural) cavity (LaFuma et al., 1980). Injection of asbestos into the peritoneal (abdominal) cavity of 20 European hamsters produced 15 abdominal tumors, while 3 were seen in the control group. Rabbits were also shown to develop mesothelioma 5 and 6 years after peritoneal injection of asbestos fibers (Pott et al., 1980). Monkeys developed asbestosis and pretumorous lesions from asbestos injection into the trachea and pleura (Pylev and Shabad, 1973; cited in Pott, 1980).
PENETRATION OF ASBESTOS FIBERS INTO THE BODY FROM THE GUT
“During the 1970s, potential health risks associated with exposure to asbestos in drinking water became a national concern. This concern developed primarily because of reports of some drinking water fiber concentrations in the range of 10,000,000-10,000,000,000 fibers/liter (Millette et al., 1979) and published observations of increased risk of gastrointestinal and peritoneal cancer among asbestos workers (Seilikoff, 1979).” This statement introduced a review paper (1983) by Philip Cook, an employee of the US Environmental Protection Agency (EPA). He continued: “One of the key questions that arose from debate over whether ingestion of mineral fibers could result in increased gastrointestinal cancer risk was whether fibers can penetrate the gastrointestinal mucosa and thus have some chance of residing in tissue. It is likely that such movement of a large number of fibers is a necessary precursor for carcinogenesis following ingestion of asbestos.”
Cook reviewed 19 reports in which tissues from animal and human subjects exposed to asbestos taken by mouth had been examined. These reports, dating from 1965 to 1982, varied a great deal. The subjects were rats, baboons, fish, and people, and several different types of asbestos were given in water, food, or by stomach tube for periods ranging from a single dose to lifetime exposure. Colon, blood, brain, lung, urine, kidney, lymph fluid, muscle, spleen, mesentery, jejunum, and esophagus were examined, mostly using transmission or scanning electron microscopy on concentrated preparations.
The results were mixed. Some studies found no indication of asbestos fibers in the tissue examined, while others clearly did. Cook observed that those studies that did report the presence of fibers were those best able to detect them, and were also least likely to have been affected by contamination. In his conclusion, Cook stated, in the cautious language of scientists, “It is difficult to conclude on the basis of the studies … that asbestos fibers do not cross the intestinal barrier.” He also estimated, based on the little evidence available, that in humans, about one fiber of every thousand in drinking water passes into the urine (Cook and Olson, 1979).
ASBESTOS GIVEN BY MOUTH: EFFECTS
Cook’s review was published in 1983, in Volume 53 of Environmental Health Perspectives. The same volume also contained a review covering studies of the cancer-causing potential of orally administered asbestos. Lyman Condie, also with the EPA, reviewed eleven studies published between 1967 and 1981. All but one used rats or hamsters. The single nonhuman primate study lasted only 5 years, a latency period Condie considered too short to allow cancer to occur if baboons reacted similarly to humans (Webster, 1974). Of the remaining 10 reports, Condie noted, “Many of the studies suffered from an insufficient number of experimental animals and from an inadequate exposure time to asbestos. Another major drawback of many of the studies was that they were not lifetime studies.”
Of the studies of 50 or more animals exposed to asbestos for 5 months or longer and observed at for least 20 months, two used rats (Gibel et al., 1976; Donham et al., 1980) and one used hamsters (Smith et al., 1980). Gibel’s group fed rats 20 milligrams daily of asbestos in the form of filters mixed with their food. The 42 rats examined developed 12 malignant tumors against only 2 in controls, a significant difference. Tumors in the experimental group occurred in the lung, kidney, nodes, and liver, and the authors noted in their summary “The localization of the tumors varied and so conclusions about organ specificity can not be drawn, when asbestos is [applied] orally.” Condie’s review was rather dismissive, saying “The authors stated that no conclusions could be made from their test results regarding the pathogenesis of the tumors caused by the oral intake of asbestos material.” This issue of tumor localization with respect to the issue of how ingested asbestos might cause cancer is discussed later.
A study of 180 hamsters given 1300 million fibers/liter water throughout their lifetime produced one peritoneal mesothelioma and two carcinomas of the forestomach as well as a lung carcinoma in the group, but the authors regarded their results as inconclusive since another 180 hamsters given 10 times that dose did not develop tumors (Smith et al., 1980). Since mesothelioma is a rare cancer generally associated with asbestos exposure, however, this does give grounds for suspecting carcinogenesis from asbestos exposure.
In the study done by Donham’s group, the bowel and rectum of 189 rats fed 10% asbestos in their diet and followed to 32 months were examined microscopically (other organs were not examined). Although the number of malignant colon tumors was not significantly different in the asbestos and control groups, when other lesions of the colon and rectum were considered, including ulcers and inflammation, the rats fed asbestos had significantly more lesions. One of the asbestos-fed rats developed mesothelioma. In light of their results, which included evidence for gut penetration by asbestos fibers and altered cell regulatory mechanisms. these authors stated “…we feel there is suggestive evidence that ingested asbestos may have some role in colon carcinogenesis….”
One of the observations made by Donham and his co-workers has great relevance to the suitability of rats as an animal model, though it was not mentioned in the review by Condie and associates. The Donham group chose the F344 strain of laboratory rats for its longevity; this strain lives an average of 30 months, and they carried their study out to 32 months. “Significantly,” they observed, “the bowel tumors were found only in very old animals (25-30 months). Investigators should consider this fact when designing future studies. Delaying until at least two years before killing any animals may enhance the detection of neoplastic or preneoplastic bowel lesions related to asbestos.”
CONCLUSIONS DRAWN FROM ANIMAL EXPERIMENTS TO 1983
From the experiments published through 1983, it was clear that direct application of asbestos into the body would cause cancer in animals. It also seemed likely that asbestos fibers penetrate the wall of the gastrointestinal tract and migrate into tissues, given that the best studies showed positive results, though some negative studies had also been published. Logically, it might be expected that if asbestos can pass into the body from the gut, and if the fibers cause cancer when in the body, animal models given asbestos by mouth should develop cancer at a greater rate than untreated controls. Some studies did show this, while others gave negative results.
Although Condie, who reviewed the oral carcinogenesis studies, pointed out serious problems with many of these studies he also noted, “One can question the suitability of the animal models employed in evaluating the human response to oral exposure to asbestos, since sufficient time may be lacking between exposure and the development of malignancies during the animal’s lifetime.” Since asbestos exposure by inhalation had induced cancer in rats, however, he concluded “one would expect to be able to produce a neoplastic [cancerous] response within the lifetime of conventional laboratory animals with massive doses of ingested asbestos such as those employed in some of the studies mentioned in this paper.” Condie left the clear implication that if ingested asbestos was dangerous to humans, this should have been demonstrable in the animal studies. Some alternative deductions are considered in the second part of this report.
HUMAN STUDIES ON THE EFFECTS OF ORAL ASBESTOS
An ethical way to study human reactions to a substance and route of exposure suspected to cause cancer is to study people who have been inadvertently exposed. In the case of water-borne asbestos, epidemiological studies were done comparing cancer rates in communities with substantial amounts of asbestos in the water supply to other communities believed to have less exposure. As of 1987, cancer death rates had been examined in seven areas of the United States and Canada. The areas examined were Duluth, Minnesota, Connecticut, Quebec, the California Bay Area including San Francisco, Utah, Puget Sound, especially Everett, Washington, and Escambia County, Florida. These epidemiological studies were reviewed by a Working Group for the Department of Health and Human Services (DHHS) Committee to Coordinate Environmental and Related Programs (CCERP), Subcommittee on Risk Assessment (Richard Lemen, Chair) (CCERP 1987).
The working group was formed “to assist policy makers in the DHHS determine if adequate information was available for a definitive risk assessment on [potential risk of cancer associated with ingestion of asbestos] … and evaluate if the weight of evidence was sufficient to prioritize this issue for new policy recommendations.”
The kind of epidemiological studies they reviewed, where an attempt is made to correlate exposure to a suspected carcinogen with cancer rates in a geographic area, have numerous problems. People move in and out of the area, carrying their exposure histories with them. Their individual exposures may be increased by occupational exposure or decreased, for example, if they use bottled water. The exposure of the population in general may not be well characterized. Factors such as occupation, race, ethnicity, socioeconomic status, and personal habits such as smoking may not be controlled. The size of the population studied may be too small to show significant differences in cancer rates unless there are extraordinary numbers of excess cancers. For cancer studies such as this one, latency is particularly important; the time from exposure to the suspected carcinogen to the time cancers are counted must exceed the time it takes for cancers to develop.
Each of the studies considered by the working group was flawed, some more than others. In the first two Duluth studies, the maximum exposure time was 15 to 20 years, possibly too short for a disease with an estimated latency of 30 to 40 years to be clearly demonstrable (Masson et al., 1974; Levy et al., 1976).
In the Connecticut studies, the latency was somewhat longer, but the exposure to asbestos may have been low.
The two Quebec studies did have a maximum duration of exposure of more than 50 years, and one study demonstrated more-than-expected (excess) numbers of cancers. These were cancers of the stomach and lung in men, and pancreas in women (Wigle, 1977). However, under the assumption that both sexes should be equally susceptible to cancer at all three sites, the author concluded that a link between cancer and asbestos in drinking water was not supported.
The population studied in the Bay Area had a maximum exposure time of more than 40 years. Significant relations were found between asbestos content in drinking water and lung cancer in men, gall bladder, pancreatic, esophagus, pleura, and kidney cancer in women, and peritoneal and stomach cancer in both sexes (Kanarek et al., 1980). A follow-up study controlling for several potentially confounding factors supported the original findings, reporting a relation between asbestos dose and cancers of the colon and prostate in men, peritoneum and pleura in women, and total cancers and cancer of the esophagus, stomach, and pancreas for both men and women (Conforti et al., 1981). A third San Francisco study suggested that population density might be an important confounding factor. Since 1974, the California Department of Health Services has recommended filters to reduce exposure in any water supply system using asbestos-laden water sources.
The Utah study suffered from an insufficient latent period, and the asbestos concentration in the drinking water was not known.
In Puget Sound, the duration of asbestos exposure was more than 40 years. One of the three studies found non-significant increases in prostate and brain cancer and leukemia in men, and cancers of the small intestine and thyroid in men and women exposed to water-borne asbestos. A case-control study of people who had been diagnosed with cancers of the GI, respiratory, and urinary systems, compared to people living in the same area who had not been diagnosed was done in Everett (Polissar et al., 1983). A significant increase in the odds of developing stomach and pharyngeal cancer in men, but not women, was found, and the authors concluded that their evidence for a link between cancer and asbestos in water was not convincing. Asbestos exposure was individually estimated based on a questionnaire asking about water consumption “5 years ago.” Considering the typical latency of asbestos-related cancer, these exposure estimates may have been inadequate.
The Escambia County, Florida study found no association between asbestos dose and cancer deaths, but the authors noted that a large number of cancer deaths would have been required to reach statistical significance.
“The collective conclusions of available reviews and our panel,” the DHHS committee (CCERP, 1987) wrote, “indicate that the information is inadequate for a credible risk assessment of cancer risks associated with the ingestion of asbestos based on information developed from studies of asbestos ingestion…. Epidemiologic studies have not definitively established the existence of an association between asbestos ingestion and gastrointestinal cancer or other cancers.” They concluded that if there is such an association, “it is probably weak compared to background cancer rates” and that “epidemiologic research methodology is limited in its ability to detect small increases in risk. If additional epidemiological research is undertaken, then it should be recognized that studies will require a substantial amount of time for completion, will be very expensive, and will probably provide only limited information about small increases in risk, possibly providing an upper estimate of risk.”
“Given the available data,” they concluded, “we do not believe that from a qualitative cancer risk assessment perspective the cancer risks associated with the ingestion of asbestos are among the most pressing environmental health hazards in the United States. Nonetheless, this should not be taken to mean that the potential hazard associated with ingested asbestos is an unimportant issue which does not warrant further research. Even if the increased rate of cancer is less than 10% of the background rate and cannot be demonstrated by available research tools, the ingestion of water, food, or drugs laden with asbestos by millions of people over their lifetimes could result in a substantial number of cancers.”
They ended their report saying, “Several of the members of this working group believe it is prudent, preventive public health policy to recommend eliminating possible sources of ingestion exposure to asbestos whenever and to whatever extent possible. This should not be interpreted as a recommendation of the Department of Health and Human Services or its member agencies. Some of the approaches which could be pursued include the following: eliminating asbestos cement pipe in water supply systems, eliminating the use of asbestos filters in the processing of beverages, foods, and medications, and reducing the levels of asbestos fibers in drinking water supplies. It should be noted that on January 29, 1986, EPA proposed prohibiting the manufacture of asbestos cement pipe; therefore, future abatement efforts of this potential exposure source may only involve replacement of existing pipe.”
STUDIES ON INGESTED ASBESTOS AND CANCER FROM THE 1980s - 2005
As matters stood at the time of several reviews written in the 1980s, the cancer-causing potential of ingested asbestos was anything but clear. Although deposition of large quantities of asbestos directly into the bodies of experimental animals clearly caused cancer, the evidence that asbestos fibers could penetrate the gut wall of experimental animals, or that asbestos in their food or water could cause cancer was equivocal. Epidemiological studies of people whose drinking water contained asbestos did not consistently demonstrate a carcinogenic effect, but they did not establish that drinking asbestos-containing water was safe, either. Further study was advised, although some reports noted that additional epidemiological studies of the type conducted thus far would be unlikely to add to then-current understanding (CCERP, 1987).
PENETRATION OF ASBESTOS FIBERS INTO THE BODY FROM THE GUT
One research group, whose negative results with asbestos fiber penetration had been cited in Cook’s review, redid their analysis (Kaczenski and Hallenbeck, 1984). Using larger amounts of tissue and a more sensitive assay for asbestos, they found that asbestos fibers could be clearly demonstrated in the tissues (stomach, heart, spleen, pancreas, blood) of a baboon which had been given asbestos by mouth, and that those fibers must have penetrated the gut wall to get there. With this reversal of one of the previously negative findings, the preponderance of the evidence appeared to show that asbestos can travel through the gut wall and into the body from exposure via the gastrointestinal tract.
A recent study (Haque et al, 2001) has also demonstrated that pups born of pregnant rats fed asbestos through a feeding tube show asbestos fibers in their bodies.
ASBESTOS GIVEN BY MOUTH: EFFECTS
In light of the known ability of asbestos to cause cancer when placed in the body, and its ability to penetrate the gut, the preponderance of negative results in animals given oral asbestos seemed difficult to explain. Donham and his coworkers (1980) had noted that in their experience, precancerous changes appeared primarily in the oldest of the rats they studied. They recommended waiting at least 24 months to look for tumors caused by asbestos ingestion early in life.
Four subsequent studies followed that advice. Two examined the effect of ingesting amosite asbestos, one in hamsters (National Toxicology Program, 1983), the other in rats (National Toxicology Program, 1990), both with essentially negative results.
A study of asbestos given in palm oil to rats (Truhaut and Chouroulinkov, 1989) showed no toxic effects and no polyps of the large intestine after 24 months. The authors noted that a similar study published in 1985 (National Toxicology Program, 1985) had shown a significant increase in polyps, and suggested that the palm oil used as a vehicle for the asbestos may have been protective. In this connection, they noted that Bolton et al. (1982), using a diet to which margarine was added, also failed to observe such polyps.
The study of the effect of chrysotile asbestos in rats (National Toxicology Program, 1985) found that ingestion of chrysotile fibers of intermediate length was associated with polyps of the large intestine, small intestine, and stomach of the males. The authors interpreted their findings as “some evidence of carcinogenicity.”
RECENT REPORTS ON INGESTED ASBESTOS IN HUMANS
In the summary report of the DHHS working group (CCERP, 1987), the epidemiological studies reported through 1987 were regarded as inconclusive. Most epidemiological studies are very blunt experimental instruments, and it is difficult to use them to establish either safety or danger from a particular agent. The advice given by the DHHS CCERP committee to consider carefully the information to be gained from large, ecologic, epidemiological studies before embarking on such expensive undertakings seems to have been followed. Only two such studies appear to have been published since 1987 (Howe et al., 1989; Browne et al., 2005).
A second summary report (Cantor, 1997) again reviewed studies done to that point and concluded, “Overall, the epidemiologic database is not adequate to evaluate the cancer risk posed by asbestos in drinking water. There are suggestions in the cited studies of elevated risks for gastric, kidney, and pancreas cancers, which warrant further investigation.”
The study published in 2005 was of cancer incidence in Woodstock, New York between 1980 and 1998 (Browne et al., 2005). Asbestos contamination in the town’s water, as much as 304.5 million fibers per liter from asbestos/concrete pipes installed in the water system in the 1950s, was discovered in 1985. The response of the New York State Department of Health was to establish “the Woodstock Asbestos Exposure Registry [WAER] to monitor rates of cancer among individuals who lived on the water supply between 1960 and 1985” (Browne et al., 2005). Cancer rates in 2936 registrants were observed from 1980-1998, with a follow-up time of 5 to 20+ years. For various reasons, including moves from the area, the data of 1852 people was actually analyzed. Their cancer rates were compared to that of New York State excluding New York City. Only pancreatic cancer showed a statistically significant increase in Woodstock, with 2.19 times the incidence of the rest of the state (excluding NYC), based on 9 observed cases. This increase was greater in men (3.08 times the expected incidence) than women (1.39 times the usual risk). Esophageal cancer in men had a relative risk of 2.91, but with such small numbers, the only statistically significant difference was in pancreatic cancer, and the authors concluded, “The general pattern of results did not demonstrate a likely link between exposure to asbestos in drinking water and cancer occurrence among participants in the WAER.”
This study, though somewhat better than most others in that only residents who were actually on the water system were included, suffered from small numbers, making statistical significance difficult to establish, and a minimally adequate latency period. The authors also assumed that the population of New York State excluding New York City (which had a level of asbestos below detectable limits; Millette et al., 1980) is relatively free of oral asbestos exposure, although several other cities in New York had asbestos levels ranging from 500,000 to nearly 1,000,000 fibers /liter (Millette et al, 1980).
Some kinds of epidemiological studies can produce more definitive results, however. A population with known heavy exposure to the substance in question can be followed in time, and their cancer incidence can be compared to that of a similar, not so exposed population. After World War II in Norway, lighthouse keepers became the unwitting guinea pigs for eventual studies on the effects of ingested asbestos.
In the 1950s, many of the 133 lighthouses along the Norwegian coast had their roof tiles replaced with asbestos-cement plates composed of 15% asbestos. Two decades later, in the late 70s, the roof tiles were found to be heavily worn. Water collected from the roofs and into the cisterns, which provided nearly all of the household needs for the lighthouse keepers and their families, contained more than 500,000,000 fibers per liter in the seven lighthouses tested (Andersen et al., 1993). This was ten thousand times more than the exposure of any other known population in Norway (50,000 fibers/liter or fewer), although some US municipalities had water supplies with a similar asbestos burden (Millette et al., 1980).
In the first of two studies, the 690 lighthouse keepers who began work between 1920 and 1966 were followed, and the cancers they experienced from 1960 to 1991 were compared to the cancers expected in a similar population of rural Norwegians (Andersen et al., 1993). More than expected numbers of stomach and colon cancer were observed, but this excess was not statistically significant in the group as a whole. Those who had 20 years or more of exposure, however, did have significantly more stomach cancer, 2.4 times as much. The authors cautiously noted that diet, a potential source of excess stomach cancer, was not controlled, the population size was small, and the time when eroding roof tiles began to release larger numbers of asbestos fibers into the drinking water could only be estimated.
In 2004, a medical case report was published of a 76-year-old woman from the Netherlands who had multiple tumors on the peritoneum, confirmed to be malignant mesothelioma. She had no occupational exposure to asbestos, but upon questioning, she told her doctors that for many years, she used to prepare vegetables for cooking in rainwater collected from a roof made of asbestos (van Kesteren et al., 2004A).
Summarizing the literature on asbestos effects in animal and epidemiologic studies to that point, the authors of this case report stated, “The overwhelming evidence that has been found in studies on the association of inhaling asbestos and pleural and peritoneal mesotheliomas has not been observed in those concerning asbestos ingestion. However, the observation that asbestos fibers can penetrate the gastro-intestinal tract and subsequently transmigrate to other tissues (CCERP, 1987) in combination with the recent finding of asbestos fibers in omentum and mesentery in subjects with peritoneal mesothelioma (Dodson et al, 2000) [raises] concern about the malignant potential of ingested asbestos fibers. We think it is therefore important to pay attention to the history of the ingestion of asbestos fibers of this woman with malignant peritoneal mesothelioma. Whether the ingestion of asbestos fibers caused her disease is speculative. The concentration of the asbestos fibers in the water this patient used and subsequently the fiber contamination in her food is unknown as well as the size of the fibers, which is an important carcinogenic determinant (CCERP, 1987). However, we consider the asbestos contamination as very likely regarding the report of a high fiber contamination (500 million fibers/l) found in cisterns supplied with runoff water from asbestos shingle roofs (CCERP, 1987).”
A few months later, a letter in response to this report appeared in the same journal. It was titled: “Asbestos in drinking water does not cause mesothelioma” (Lange and Hoskins, 2004). Based on their interpretation of the literature, they said “…it appears that that [sic] ingestion of asbestos in water, even at high levels, does not result in mesothelioma and other cancers. Reports suggesting a relationship of asbestos in water and cancer, particularly mesothelioma, should be considered spurious.”
“We believe it was important to pay attention to the history of the ingestion of asbestos fibers in our patient,” replied the authors of the case report (van Kesteren et al., 2004B), “because:
1. Malignant peritoneal mesothelioma is clearly related to asbestos exposure (DHHS committee [CCERP], 1987; Antman et al., 2001).
2. Asbestos fibers can penetrate the gastrointestinal tract and subsequently transmigrate to other tissues (DHHS Committee [CCERP], 1987).
3. Asbestos fibers are found in omentum and mesentary in subjects with peritoneal mesothelioma (Dodson et al., 2000).”
They concluded, saying, “We think that one should not ignore the potential risk factors of a disease whose pathogenesis is far from revealed. Therefore, we feel that it is important to question a patient with malignant peritoneal mesothelioma for any kind of asbestos exposure in the past, including asbestos ingestion.”
2005 saw the publication of an update on the Norwegian lighthouse keepers (Kjaerheim et al., 2005). This time, those first employed between 1917 and 1967, and born after 1884 and alive in 1960, were followed up for cancer incidence from 1960 to 2002. These 726 men were subdivided according to exposure; 107 of them had worked at one of the 21 lighthouses that received their water from asbestos-concrete roofs, while 479 had been mostly unexposed and the exposure of 140 was unknown. Because lighthouse reconstruction (and installation of asbestos roofing) took place between 1945 and 1950, 1948 was chosen as the beginning of exposure.
The definitely exposed group had 2.5 times as much stomach cancer as expected, and more cancer of the kidney and small intestine than expected as well. Small numbers (e.g. 6 stomach cancers in the exposed group) prevented the cancer incidence in the subdivided groups from reaching statistical significance, but taken as a whole, the lighthouse keepers showed a significant elevation of stomach cancer (1.6 times that expected) and gastrointestinal cancer generally (1.4 times that expected). Those exposed 20 years or more had elevated rates of stomach, colon, and gastrointestinal cancer. The stomach cancer rates after 20 years of exposure, at 1.7 times the number expected, showed definite statistical significance. (The expected percentage of men who develop gastrointestinal cancer at some time in their lives in rural Norway is 5.9% (calculated from Kjaerheim et al., 2005), while the observed percent was 8.5%, giving an excess incidence of 2.6%.)
The possible role of diet in explaining the excess stomach cancers was considered and found unlikely. The authors concluded, “results support the hypothesis of an association between ingested asbestos and gastrointestinal cancer risk, and stomach cancer specifically.”
Their final statement, “… the limited excess risk found in this heavily exposed group does not indicate that asbestos in drinking water is a major health problem in the general population” is doubtless intended to be reassuring. Perhaps it is, for Norwegians.
About 10% of 406 US cities tested had drinking water with asbestos fiber concentrations above 10 million fibers per liter (Millette et al., 1980), sometimes with over 600 million fibers per liter (Cook et al., 1976, cited in Millette et al., 1980), comparable to the exposure reported for the lighthouse keepers (maximum 500 million fibers/ liter). One tenth of the US population is about 29,780,000 people. If they experience the 2.6% excess gastrointestinal cancers observed in men with similar heavy exposure in their lifetime, nearly 800,000 Americans develop gastrointestinal cancer from asbestos in their drinking water. Presumably, lower doses result in a lower cancer incidence, but roughly 36% of Americans, 100,000,000 of them, drink water containing 500,000 to 10,000,000 asbestos fibers per liter (Millette et al., 1980). Even a low excess cancer incidence would affect many, many people.
Heavy asbestos contamination of household water apparently also leads to increased airborne asbestos (Webber et al., 1988). This is another factor (inhaled asbestos is a well known carcinogen) that has not been seriously considered in the debate surrounding the question of whether asbestos in drinking water can cause cancer.
CONCLUSIONS
As information about the effects of ingested asbestos accumulates, it is becoming clear that although the latency period is long and the effect size is possibly small relative to that of inhaled asbestos, asbestos taken by mouth does cause cancer in humans.
In terms of responsible action to ensure the safety of water users, this means that the 200,000+ miles of asbestos/concrete water pipe in the United States (Millette et al., 1980) will need to be replaced with a safe substitute as quickly as possible. Communities whose water naturally contains asbestos will need to find improved ways to reduce the potential danger. Users of water catchment systems must be made aware of the danger of
using asbestos-containing components in the system, and asbestos/concrete pipes should not be sold, here or abroad, for the purpose of transporting drinking water.
It is interesting to look back and consider what would have had to have been different to avoid the present situation, in which hundreds of millions of people are being exposed to a carcinogen in the water they use for drinking and cooking. A requirement for proof of safety before a new product is put into general use, similar to the present system for testing pharmaceuticals, might have prevented this situation. (See, for example, http://www.asmalldoseof.org/ for a presentation of the precautionary principle.)
There were early indications that asbestos in the body caused cancer, and that fibers could penetrate the gut. The exclusive reliance on rodent animal models of carcinogenesis was evidently unwise, though there were definite warning signs in the finding of precancerous changes in rats with a lifetime exposure to oral asbestos and the occasional findings of mesothelioma, always in experimental rodents, never in controls (Smith et al., 1980; Donham et al., 1980; Hilding et al., 1981). It may be that rats simply do not live long enough to develop full-blown cancer from their exposure, or other species differences may explain why humans get gastrointestinal cancer from oral asbestos when rodents do not do so to a significant extent.
Considering the thalidomide disaster, this will not be the first instance in which limited use of animal models for safety assessment has led to misplaced confidence in product safety. Thalidomide, the drug given to pregnant women in Europe for morning sickness in the late 50s and early 60s, was tested in rats and found to have no adverse effects. An application to sell the drug in the US was submitted, but later withdrawn, when babies born to women taking the drug were stillborn or had severe birth defects- missing or malformed arms and legs. Decades later, it was learned that all nonhuman primate species tested except the distantly related prosimian Galago crassicaudatus are susceptible to birth defects from thalidomide (Hendrickx, 1973; Hendrickx and Newman, 1973; Hendrickx and Sawyer, 1978). Primate models are generally much closer to humans in their responses to carcinogens and toxicants, but the only report on nonhuman primates used to test oral asbestos examined baboons after 5 years or less (Webster, 1974), a latency period likely too short for asbestos-caused cancer to develop in primates.
The history of population studies on the effects of asbestos in drinking water is a virtual textbook demonstration of drawbacks to attempting to use ecologic epidemiological methods to establish the safety or danger of a suspected carcinogen.
The danger of inhaled asbestos was established relatively early because people with a known heavy exposure could be followed individually, though the latency to develop cancer from asbestos inhalation is typically 30-40 years.
In contrast, until the Norwegian lighthouse keepers were studied, inhabitants of cities with asbestos in the water supply were the only populations available for study. Unlike the lighthouse keepers, whose employment records at individual lighthouses, and hence exposure, could be individually determined, the city dwellers, for the most part, were not followed individually; they drank water with asbestos content that varied with rainfall, acidity, and their location in relation to the water system (unless they used bottled water), and, being mobile Americans, were often no longer living in the city under study after 20 to 40 years.
There must have been a great impetus to know if oral asbestos caused cancer at the time its presence in water supplies was discovered; several studies were conducted before sufficient time had passed to expect cancers to have developed (CCERP, 1987).
Even with all their drawbacks, some of the population studies did show statistically significant increases in cancer rates in association with asbestos in drinking water.
In the 1970’s, another property of asbestos became too obvious to ignore. Exposure to asbestos can cause death.
Workers exposed to asbestos in their jobs became ill and died of particular diseases. Over time, it was discovered that exposure to airborne asbestos fibers could lead, decades later, to asbestosis, lung cancer, and mesothelioma, a cancer of the lining of the body cavities. Mesothelioma is a hallmark of asbestos exposure; it is a distinctive and, even now, extremely rare form of cancer. About 15-20 cases occur per million men each year in North America, and far fewer women develop the disease. Almost every person who has ever developed mesothelioma has had occupational exposure to asbestos at least 15 years prior, and sometimes as long as 70 years before. The peak in incidence occurs 30 to 40 years after exposure (Sporn and Roggli, 2004).
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Other kinds of cancer also showed up decades after asbestos exposure. By the early 80’s, five studies had shown that cancers of the stomach and other parts of the gastrointestinal (GI) system occurred at higher rates in asbestos workers. The risk ranged from somewhat higher than non-exposed control workers (1.32 in London factory workers) to almost 3 times the usual risk in New York and New Jersey insulation workers (Safe Drinking Water Committee, 1983). It became clear that at least some GI cancers are likely related to asbestos exposure (Rolston and Oury, 2004).
What was not clear was whether inhaled asbestos fibers had migrated through the body from the lungs to cause these cancers, or whether fibers from the lungs, coughed up and then swallowed, might have entered the stomach and other digestive organs more directly, from ingestion.
This question was important then, and is still important now, because, as noted above, hundreds of thousands of miles of asbestos/concrete pipe are used to transport the drinking water for many Americans. This pipe is known to shed asbestos fibers (Safe Drinking Water Committee, 1983). Even at relatively low exposures, if swallowed asbestos can cause cancer, exposing millions of people to asbestos in their drinking water could be considered dangerous (CCERP, 1987).
This report reviews the scientific literature relating to the possible carcinogenicity (cancer-causing ability) of asbestos taken by mouth, as in drinking water. Because reviews of this literature in the 1980s had a substantial impact on public policy regarding asbestos in drinking water, I summarize that literature first. I then review literature to 2005 and discuss the impact of the more recent findings on our current knowledge concerning the carcinogenicity of asbestos in drinking water.
STUDIES ON INGESTED ASBESTOS AND CANCER THROUGH THE ‘80s
A number of scientific studies done in the 1970’s and 1980’s addressed the question of whether swallowed asbestos could cause cancer. Since it is unethical to deliberately expose people to suspected cancer-causing agents unless it is considered beneficial to them, the studies used animal models and “natural experiments” in which humans had been exposed to asbestos in their drinking water. The many approaches to this question in animal models included direct injection or surgical implantation of asbestos into the body followed by examination for tumors, testing of whether asbestos given by mouth could penetrate body tissues, and administration of asbestos in food or water followed by examination for tumors.
DIRECT INJECTION OF ASBESTOS: EFFECTS
Several studies established that direct injection or surgical implantation of asbestos into the body cavities of rats and hamsters produced tumors. Forty-one rats injected with asbestos into the lung cavity, for example, developed 5 mesotheliomas in the abdomen in addition to 20 mesotheliomas of the lining of the lung (pleural) cavity (LaFuma et al., 1980). Injection of asbestos into the peritoneal (abdominal) cavity of 20 European hamsters produced 15 abdominal tumors, while 3 were seen in the control group. Rabbits were also shown to develop mesothelioma 5 and 6 years after peritoneal injection of asbestos fibers (Pott et al., 1980). Monkeys developed asbestosis and pretumorous lesions from asbestos injection into the trachea and pleura (Pylev and Shabad, 1973; cited in Pott, 1980).
PENETRATION OF ASBESTOS FIBERS INTO THE BODY FROM THE GUT
“During the 1970s, potential health risks associated with exposure to asbestos in drinking water became a national concern. This concern developed primarily because of reports of some drinking water fiber concentrations in the range of 10,000,000-10,000,000,000 fibers/liter (Millette et al., 1979) and published observations of increased risk of gastrointestinal and peritoneal cancer among asbestos workers (Seilikoff, 1979).” This statement introduced a review paper (1983) by Philip Cook, an employee of the US Environmental Protection Agency (EPA). He continued: “One of the key questions that arose from debate over whether ingestion of mineral fibers could result in increased gastrointestinal cancer risk was whether fibers can penetrate the gastrointestinal mucosa and thus have some chance of residing in tissue. It is likely that such movement of a large number of fibers is a necessary precursor for carcinogenesis following ingestion of asbestos.”
Cook reviewed 19 reports in which tissues from animal and human subjects exposed to asbestos taken by mouth had been examined. These reports, dating from 1965 to 1982, varied a great deal. The subjects were rats, baboons, fish, and people, and several different types of asbestos were given in water, food, or by stomach tube for periods ranging from a single dose to lifetime exposure. Colon, blood, brain, lung, urine, kidney, lymph fluid, muscle, spleen, mesentery, jejunum, and esophagus were examined, mostly using transmission or scanning electron microscopy on concentrated preparations.
The results were mixed. Some studies found no indication of asbestos fibers in the tissue examined, while others clearly did. Cook observed that those studies that did report the presence of fibers were those best able to detect them, and were also least likely to have been affected by contamination. In his conclusion, Cook stated, in the cautious language of scientists, “It is difficult to conclude on the basis of the studies … that asbestos fibers do not cross the intestinal barrier.” He also estimated, based on the little evidence available, that in humans, about one fiber of every thousand in drinking water passes into the urine (Cook and Olson, 1979).
ASBESTOS GIVEN BY MOUTH: EFFECTS
Cook’s review was published in 1983, in Volume 53 of Environmental Health Perspectives. The same volume also contained a review covering studies of the cancer-causing potential of orally administered asbestos. Lyman Condie, also with the EPA, reviewed eleven studies published between 1967 and 1981. All but one used rats or hamsters. The single nonhuman primate study lasted only 5 years, a latency period Condie considered too short to allow cancer to occur if baboons reacted similarly to humans (Webster, 1974). Of the remaining 10 reports, Condie noted, “Many of the studies suffered from an insufficient number of experimental animals and from an inadequate exposure time to asbestos. Another major drawback of many of the studies was that they were not lifetime studies.”
Of the studies of 50 or more animals exposed to asbestos for 5 months or longer and observed at for least 20 months, two used rats (Gibel et al., 1976; Donham et al., 1980) and one used hamsters (Smith et al., 1980). Gibel’s group fed rats 20 milligrams daily of asbestos in the form of filters mixed with their food. The 42 rats examined developed 12 malignant tumors against only 2 in controls, a significant difference. Tumors in the experimental group occurred in the lung, kidney, nodes, and liver, and the authors noted in their summary “The localization of the tumors varied and so conclusions about organ specificity can not be drawn, when asbestos is [applied] orally.” Condie’s review was rather dismissive, saying “The authors stated that no conclusions could be made from their test results regarding the pathogenesis of the tumors caused by the oral intake of asbestos material.” This issue of tumor localization with respect to the issue of how ingested asbestos might cause cancer is discussed later.
A study of 180 hamsters given 1300 million fibers/liter water throughout their lifetime produced one peritoneal mesothelioma and two carcinomas of the forestomach as well as a lung carcinoma in the group, but the authors regarded their results as inconclusive since another 180 hamsters given 10 times that dose did not develop tumors (Smith et al., 1980). Since mesothelioma is a rare cancer generally associated with asbestos exposure, however, this does give grounds for suspecting carcinogenesis from asbestos exposure.
In the study done by Donham’s group, the bowel and rectum of 189 rats fed 10% asbestos in their diet and followed to 32 months were examined microscopically (other organs were not examined). Although the number of malignant colon tumors was not significantly different in the asbestos and control groups, when other lesions of the colon and rectum were considered, including ulcers and inflammation, the rats fed asbestos had significantly more lesions. One of the asbestos-fed rats developed mesothelioma. In light of their results, which included evidence for gut penetration by asbestos fibers and altered cell regulatory mechanisms. these authors stated “…we feel there is suggestive evidence that ingested asbestos may have some role in colon carcinogenesis….”
One of the observations made by Donham and his co-workers has great relevance to the suitability of rats as an animal model, though it was not mentioned in the review by Condie and associates. The Donham group chose the F344 strain of laboratory rats for its longevity; this strain lives an average of 30 months, and they carried their study out to 32 months. “Significantly,” they observed, “the bowel tumors were found only in very old animals (25-30 months). Investigators should consider this fact when designing future studies. Delaying until at least two years before killing any animals may enhance the detection of neoplastic or preneoplastic bowel lesions related to asbestos.”
CONCLUSIONS DRAWN FROM ANIMAL EXPERIMENTS TO 1983
From the experiments published through 1983, it was clear that direct application of asbestos into the body would cause cancer in animals. It also seemed likely that asbestos fibers penetrate the wall of the gastrointestinal tract and migrate into tissues, given that the best studies showed positive results, though some negative studies had also been published. Logically, it might be expected that if asbestos can pass into the body from the gut, and if the fibers cause cancer when in the body, animal models given asbestos by mouth should develop cancer at a greater rate than untreated controls. Some studies did show this, while others gave negative results.
Although Condie, who reviewed the oral carcinogenesis studies, pointed out serious problems with many of these studies he also noted, “One can question the suitability of the animal models employed in evaluating the human response to oral exposure to asbestos, since sufficient time may be lacking between exposure and the development of malignancies during the animal’s lifetime.” Since asbestos exposure by inhalation had induced cancer in rats, however, he concluded “one would expect to be able to produce a neoplastic [cancerous] response within the lifetime of conventional laboratory animals with massive doses of ingested asbestos such as those employed in some of the studies mentioned in this paper.” Condie left the clear implication that if ingested asbestos was dangerous to humans, this should have been demonstrable in the animal studies. Some alternative deductions are considered in the second part of this report.
HUMAN STUDIES ON THE EFFECTS OF ORAL ASBESTOS
An ethical way to study human reactions to a substance and route of exposure suspected to cause cancer is to study people who have been inadvertently exposed. In the case of water-borne asbestos, epidemiological studies were done comparing cancer rates in communities with substantial amounts of asbestos in the water supply to other communities believed to have less exposure. As of 1987, cancer death rates had been examined in seven areas of the United States and Canada. The areas examined were Duluth, Minnesota, Connecticut, Quebec, the California Bay Area including San Francisco, Utah, Puget Sound, especially Everett, Washington, and Escambia County, Florida. These epidemiological studies were reviewed by a Working Group for the Department of Health and Human Services (DHHS) Committee to Coordinate Environmental and Related Programs (CCERP), Subcommittee on Risk Assessment (Richard Lemen, Chair) (CCERP 1987).
The working group was formed “to assist policy makers in the DHHS determine if adequate information was available for a definitive risk assessment on [potential risk of cancer associated with ingestion of asbestos] … and evaluate if the weight of evidence was sufficient to prioritize this issue for new policy recommendations.”
The kind of epidemiological studies they reviewed, where an attempt is made to correlate exposure to a suspected carcinogen with cancer rates in a geographic area, have numerous problems. People move in and out of the area, carrying their exposure histories with them. Their individual exposures may be increased by occupational exposure or decreased, for example, if they use bottled water. The exposure of the population in general may not be well characterized. Factors such as occupation, race, ethnicity, socioeconomic status, and personal habits such as smoking may not be controlled. The size of the population studied may be too small to show significant differences in cancer rates unless there are extraordinary numbers of excess cancers. For cancer studies such as this one, latency is particularly important; the time from exposure to the suspected carcinogen to the time cancers are counted must exceed the time it takes for cancers to develop.
Each of the studies considered by the working group was flawed, some more than others. In the first two Duluth studies, the maximum exposure time was 15 to 20 years, possibly too short for a disease with an estimated latency of 30 to 40 years to be clearly demonstrable (Masson et al., 1974; Levy et al., 1976).
In the Connecticut studies, the latency was somewhat longer, but the exposure to asbestos may have been low.
The two Quebec studies did have a maximum duration of exposure of more than 50 years, and one study demonstrated more-than-expected (excess) numbers of cancers. These were cancers of the stomach and lung in men, and pancreas in women (Wigle, 1977). However, under the assumption that both sexes should be equally susceptible to cancer at all three sites, the author concluded that a link between cancer and asbestos in drinking water was not supported.
The population studied in the Bay Area had a maximum exposure time of more than 40 years. Significant relations were found between asbestos content in drinking water and lung cancer in men, gall bladder, pancreatic, esophagus, pleura, and kidney cancer in women, and peritoneal and stomach cancer in both sexes (Kanarek et al., 1980). A follow-up study controlling for several potentially confounding factors supported the original findings, reporting a relation between asbestos dose and cancers of the colon and prostate in men, peritoneum and pleura in women, and total cancers and cancer of the esophagus, stomach, and pancreas for both men and women (Conforti et al., 1981). A third San Francisco study suggested that population density might be an important confounding factor. Since 1974, the California Department of Health Services has recommended filters to reduce exposure in any water supply system using asbestos-laden water sources.
The Utah study suffered from an insufficient latent period, and the asbestos concentration in the drinking water was not known.
In Puget Sound, the duration of asbestos exposure was more than 40 years. One of the three studies found non-significant increases in prostate and brain cancer and leukemia in men, and cancers of the small intestine and thyroid in men and women exposed to water-borne asbestos. A case-control study of people who had been diagnosed with cancers of the GI, respiratory, and urinary systems, compared to people living in the same area who had not been diagnosed was done in Everett (Polissar et al., 1983). A significant increase in the odds of developing stomach and pharyngeal cancer in men, but not women, was found, and the authors concluded that their evidence for a link between cancer and asbestos in water was not convincing. Asbestos exposure was individually estimated based on a questionnaire asking about water consumption “5 years ago.” Considering the typical latency of asbestos-related cancer, these exposure estimates may have been inadequate.
The Escambia County, Florida study found no association between asbestos dose and cancer deaths, but the authors noted that a large number of cancer deaths would have been required to reach statistical significance.
“The collective conclusions of available reviews and our panel,” the DHHS committee (CCERP, 1987) wrote, “indicate that the information is inadequate for a credible risk assessment of cancer risks associated with the ingestion of asbestos based on information developed from studies of asbestos ingestion…. Epidemiologic studies have not definitively established the existence of an association between asbestos ingestion and gastrointestinal cancer or other cancers.” They concluded that if there is such an association, “it is probably weak compared to background cancer rates” and that “epidemiologic research methodology is limited in its ability to detect small increases in risk. If additional epidemiological research is undertaken, then it should be recognized that studies will require a substantial amount of time for completion, will be very expensive, and will probably provide only limited information about small increases in risk, possibly providing an upper estimate of risk.”
“Given the available data,” they concluded, “we do not believe that from a qualitative cancer risk assessment perspective the cancer risks associated with the ingestion of asbestos are among the most pressing environmental health hazards in the United States. Nonetheless, this should not be taken to mean that the potential hazard associated with ingested asbestos is an unimportant issue which does not warrant further research. Even if the increased rate of cancer is less than 10% of the background rate and cannot be demonstrated by available research tools, the ingestion of water, food, or drugs laden with asbestos by millions of people over their lifetimes could result in a substantial number of cancers.”
They ended their report saying, “Several of the members of this working group believe it is prudent, preventive public health policy to recommend eliminating possible sources of ingestion exposure to asbestos whenever and to whatever extent possible. This should not be interpreted as a recommendation of the Department of Health and Human Services or its member agencies. Some of the approaches which could be pursued include the following: eliminating asbestos cement pipe in water supply systems, eliminating the use of asbestos filters in the processing of beverages, foods, and medications, and reducing the levels of asbestos fibers in drinking water supplies. It should be noted that on January 29, 1986, EPA proposed prohibiting the manufacture of asbestos cement pipe; therefore, future abatement efforts of this potential exposure source may only involve replacement of existing pipe.”
STUDIES ON INGESTED ASBESTOS AND CANCER FROM THE 1980s - 2005
As matters stood at the time of several reviews written in the 1980s, the cancer-causing potential of ingested asbestos was anything but clear. Although deposition of large quantities of asbestos directly into the bodies of experimental animals clearly caused cancer, the evidence that asbestos fibers could penetrate the gut wall of experimental animals, or that asbestos in their food or water could cause cancer was equivocal. Epidemiological studies of people whose drinking water contained asbestos did not consistently demonstrate a carcinogenic effect, but they did not establish that drinking asbestos-containing water was safe, either. Further study was advised, although some reports noted that additional epidemiological studies of the type conducted thus far would be unlikely to add to then-current understanding (CCERP, 1987).
PENETRATION OF ASBESTOS FIBERS INTO THE BODY FROM THE GUT
One research group, whose negative results with asbestos fiber penetration had been cited in Cook’s review, redid their analysis (Kaczenski and Hallenbeck, 1984). Using larger amounts of tissue and a more sensitive assay for asbestos, they found that asbestos fibers could be clearly demonstrated in the tissues (stomach, heart, spleen, pancreas, blood) of a baboon which had been given asbestos by mouth, and that those fibers must have penetrated the gut wall to get there. With this reversal of one of the previously negative findings, the preponderance of the evidence appeared to show that asbestos can travel through the gut wall and into the body from exposure via the gastrointestinal tract.
A recent study (Haque et al, 2001) has also demonstrated that pups born of pregnant rats fed asbestos through a feeding tube show asbestos fibers in their bodies.
ASBESTOS GIVEN BY MOUTH: EFFECTS
In light of the known ability of asbestos to cause cancer when placed in the body, and its ability to penetrate the gut, the preponderance of negative results in animals given oral asbestos seemed difficult to explain. Donham and his coworkers (1980) had noted that in their experience, precancerous changes appeared primarily in the oldest of the rats they studied. They recommended waiting at least 24 months to look for tumors caused by asbestos ingestion early in life.
Four subsequent studies followed that advice. Two examined the effect of ingesting amosite asbestos, one in hamsters (National Toxicology Program, 1983), the other in rats (National Toxicology Program, 1990), both with essentially negative results.
A study of asbestos given in palm oil to rats (Truhaut and Chouroulinkov, 1989) showed no toxic effects and no polyps of the large intestine after 24 months. The authors noted that a similar study published in 1985 (National Toxicology Program, 1985) had shown a significant increase in polyps, and suggested that the palm oil used as a vehicle for the asbestos may have been protective. In this connection, they noted that Bolton et al. (1982), using a diet to which margarine was added, also failed to observe such polyps.
The study of the effect of chrysotile asbestos in rats (National Toxicology Program, 1985) found that ingestion of chrysotile fibers of intermediate length was associated with polyps of the large intestine, small intestine, and stomach of the males. The authors interpreted their findings as “some evidence of carcinogenicity.”
RECENT REPORTS ON INGESTED ASBESTOS IN HUMANS
In the summary report of the DHHS working group (CCERP, 1987), the epidemiological studies reported through 1987 were regarded as inconclusive. Most epidemiological studies are very blunt experimental instruments, and it is difficult to use them to establish either safety or danger from a particular agent. The advice given by the DHHS CCERP committee to consider carefully the information to be gained from large, ecologic, epidemiological studies before embarking on such expensive undertakings seems to have been followed. Only two such studies appear to have been published since 1987 (Howe et al., 1989; Browne et al., 2005).
A second summary report (Cantor, 1997) again reviewed studies done to that point and concluded, “Overall, the epidemiologic database is not adequate to evaluate the cancer risk posed by asbestos in drinking water. There are suggestions in the cited studies of elevated risks for gastric, kidney, and pancreas cancers, which warrant further investigation.”
The study published in 2005 was of cancer incidence in Woodstock, New York between 1980 and 1998 (Browne et al., 2005). Asbestos contamination in the town’s water, as much as 304.5 million fibers per liter from asbestos/concrete pipes installed in the water system in the 1950s, was discovered in 1985. The response of the New York State Department of Health was to establish “the Woodstock Asbestos Exposure Registry [WAER] to monitor rates of cancer among individuals who lived on the water supply between 1960 and 1985” (Browne et al., 2005). Cancer rates in 2936 registrants were observed from 1980-1998, with a follow-up time of 5 to 20+ years. For various reasons, including moves from the area, the data of 1852 people was actually analyzed. Their cancer rates were compared to that of New York State excluding New York City. Only pancreatic cancer showed a statistically significant increase in Woodstock, with 2.19 times the incidence of the rest of the state (excluding NYC), based on 9 observed cases. This increase was greater in men (3.08 times the expected incidence) than women (1.39 times the usual risk). Esophageal cancer in men had a relative risk of 2.91, but with such small numbers, the only statistically significant difference was in pancreatic cancer, and the authors concluded, “The general pattern of results did not demonstrate a likely link between exposure to asbestos in drinking water and cancer occurrence among participants in the WAER.”
This study, though somewhat better than most others in that only residents who were actually on the water system were included, suffered from small numbers, making statistical significance difficult to establish, and a minimally adequate latency period. The authors also assumed that the population of New York State excluding New York City (which had a level of asbestos below detectable limits; Millette et al., 1980) is relatively free of oral asbestos exposure, although several other cities in New York had asbestos levels ranging from 500,000 to nearly 1,000,000 fibers /liter (Millette et al, 1980).
Some kinds of epidemiological studies can produce more definitive results, however. A population with known heavy exposure to the substance in question can be followed in time, and their cancer incidence can be compared to that of a similar, not so exposed population. After World War II in Norway, lighthouse keepers became the unwitting guinea pigs for eventual studies on the effects of ingested asbestos.
In the 1950s, many of the 133 lighthouses along the Norwegian coast had their roof tiles replaced with asbestos-cement plates composed of 15% asbestos. Two decades later, in the late 70s, the roof tiles were found to be heavily worn. Water collected from the roofs and into the cisterns, which provided nearly all of the household needs for the lighthouse keepers and their families, contained more than 500,000,000 fibers per liter in the seven lighthouses tested (Andersen et al., 1993). This was ten thousand times more than the exposure of any other known population in Norway (50,000 fibers/liter or fewer), although some US municipalities had water supplies with a similar asbestos burden (Millette et al., 1980).
In the first of two studies, the 690 lighthouse keepers who began work between 1920 and 1966 were followed, and the cancers they experienced from 1960 to 1991 were compared to the cancers expected in a similar population of rural Norwegians (Andersen et al., 1993). More than expected numbers of stomach and colon cancer were observed, but this excess was not statistically significant in the group as a whole. Those who had 20 years or more of exposure, however, did have significantly more stomach cancer, 2.4 times as much. The authors cautiously noted that diet, a potential source of excess stomach cancer, was not controlled, the population size was small, and the time when eroding roof tiles began to release larger numbers of asbestos fibers into the drinking water could only be estimated.
In 2004, a medical case report was published of a 76-year-old woman from the Netherlands who had multiple tumors on the peritoneum, confirmed to be malignant mesothelioma. She had no occupational exposure to asbestos, but upon questioning, she told her doctors that for many years, she used to prepare vegetables for cooking in rainwater collected from a roof made of asbestos (van Kesteren et al., 2004A).
Summarizing the literature on asbestos effects in animal and epidemiologic studies to that point, the authors of this case report stated, “The overwhelming evidence that has been found in studies on the association of inhaling asbestos and pleural and peritoneal mesotheliomas has not been observed in those concerning asbestos ingestion. However, the observation that asbestos fibers can penetrate the gastro-intestinal tract and subsequently transmigrate to other tissues (CCERP, 1987) in combination with the recent finding of asbestos fibers in omentum and mesentery in subjects with peritoneal mesothelioma (Dodson et al, 2000) [raises] concern about the malignant potential of ingested asbestos fibers. We think it is therefore important to pay attention to the history of the ingestion of asbestos fibers of this woman with malignant peritoneal mesothelioma. Whether the ingestion of asbestos fibers caused her disease is speculative. The concentration of the asbestos fibers in the water this patient used and subsequently the fiber contamination in her food is unknown as well as the size of the fibers, which is an important carcinogenic determinant (CCERP, 1987). However, we consider the asbestos contamination as very likely regarding the report of a high fiber contamination (500 million fibers/l) found in cisterns supplied with runoff water from asbestos shingle roofs (CCERP, 1987).”
A few months later, a letter in response to this report appeared in the same journal. It was titled: “Asbestos in drinking water does not cause mesothelioma” (Lange and Hoskins, 2004). Based on their interpretation of the literature, they said “…it appears that that [sic] ingestion of asbestos in water, even at high levels, does not result in mesothelioma and other cancers. Reports suggesting a relationship of asbestos in water and cancer, particularly mesothelioma, should be considered spurious.”
“We believe it was important to pay attention to the history of the ingestion of asbestos fibers in our patient,” replied the authors of the case report (van Kesteren et al., 2004B), “because:
1. Malignant peritoneal mesothelioma is clearly related to asbestos exposure (DHHS committee [CCERP], 1987; Antman et al., 2001).
2. Asbestos fibers can penetrate the gastrointestinal tract and subsequently transmigrate to other tissues (DHHS Committee [CCERP], 1987).
3. Asbestos fibers are found in omentum and mesentary in subjects with peritoneal mesothelioma (Dodson et al., 2000).”
They concluded, saying, “We think that one should not ignore the potential risk factors of a disease whose pathogenesis is far from revealed. Therefore, we feel that it is important to question a patient with malignant peritoneal mesothelioma for any kind of asbestos exposure in the past, including asbestos ingestion.”
2005 saw the publication of an update on the Norwegian lighthouse keepers (Kjaerheim et al., 2005). This time, those first employed between 1917 and 1967, and born after 1884 and alive in 1960, were followed up for cancer incidence from 1960 to 2002. These 726 men were subdivided according to exposure; 107 of them had worked at one of the 21 lighthouses that received their water from asbestos-concrete roofs, while 479 had been mostly unexposed and the exposure of 140 was unknown. Because lighthouse reconstruction (and installation of asbestos roofing) took place between 1945 and 1950, 1948 was chosen as the beginning of exposure.
The definitely exposed group had 2.5 times as much stomach cancer as expected, and more cancer of the kidney and small intestine than expected as well. Small numbers (e.g. 6 stomach cancers in the exposed group) prevented the cancer incidence in the subdivided groups from reaching statistical significance, but taken as a whole, the lighthouse keepers showed a significant elevation of stomach cancer (1.6 times that expected) and gastrointestinal cancer generally (1.4 times that expected). Those exposed 20 years or more had elevated rates of stomach, colon, and gastrointestinal cancer. The stomach cancer rates after 20 years of exposure, at 1.7 times the number expected, showed definite statistical significance. (The expected percentage of men who develop gastrointestinal cancer at some time in their lives in rural Norway is 5.9% (calculated from Kjaerheim et al., 2005), while the observed percent was 8.5%, giving an excess incidence of 2.6%.)
The possible role of diet in explaining the excess stomach cancers was considered and found unlikely. The authors concluded, “results support the hypothesis of an association between ingested asbestos and gastrointestinal cancer risk, and stomach cancer specifically.”
Their final statement, “… the limited excess risk found in this heavily exposed group does not indicate that asbestos in drinking water is a major health problem in the general population” is doubtless intended to be reassuring. Perhaps it is, for Norwegians.
About 10% of 406 US cities tested had drinking water with asbestos fiber concentrations above 10 million fibers per liter (Millette et al., 1980), sometimes with over 600 million fibers per liter (Cook et al., 1976, cited in Millette et al., 1980), comparable to the exposure reported for the lighthouse keepers (maximum 500 million fibers/ liter). One tenth of the US population is about 29,780,000 people. If they experience the 2.6% excess gastrointestinal cancers observed in men with similar heavy exposure in their lifetime, nearly 800,000 Americans develop gastrointestinal cancer from asbestos in their drinking water. Presumably, lower doses result in a lower cancer incidence, but roughly 36% of Americans, 100,000,000 of them, drink water containing 500,000 to 10,000,000 asbestos fibers per liter (Millette et al., 1980). Even a low excess cancer incidence would affect many, many people.
Heavy asbestos contamination of household water apparently also leads to increased airborne asbestos (Webber et al., 1988). This is another factor (inhaled asbestos is a well known carcinogen) that has not been seriously considered in the debate surrounding the question of whether asbestos in drinking water can cause cancer.
CONCLUSIONS
As information about the effects of ingested asbestos accumulates, it is becoming clear that although the latency period is long and the effect size is possibly small relative to that of inhaled asbestos, asbestos taken by mouth does cause cancer in humans.
In terms of responsible action to ensure the safety of water users, this means that the 200,000+ miles of asbestos/concrete water pipe in the United States (Millette et al., 1980) will need to be replaced with a safe substitute as quickly as possible. Communities whose water naturally contains asbestos will need to find improved ways to reduce the potential danger. Users of water catchment systems must be made aware of the danger of
using asbestos-containing components in the system, and asbestos/concrete pipes should not be sold, here or abroad, for the purpose of transporting drinking water.
It is interesting to look back and consider what would have had to have been different to avoid the present situation, in which hundreds of millions of people are being exposed to a carcinogen in the water they use for drinking and cooking. A requirement for proof of safety before a new product is put into general use, similar to the present system for testing pharmaceuticals, might have prevented this situation. (See, for example, http://www.asmalldoseof.org/ for a presentation of the precautionary principle.)
There were early indications that asbestos in the body caused cancer, and that fibers could penetrate the gut. The exclusive reliance on rodent animal models of carcinogenesis was evidently unwise, though there were definite warning signs in the finding of precancerous changes in rats with a lifetime exposure to oral asbestos and the occasional findings of mesothelioma, always in experimental rodents, never in controls (Smith et al., 1980; Donham et al., 1980; Hilding et al., 1981). It may be that rats simply do not live long enough to develop full-blown cancer from their exposure, or other species differences may explain why humans get gastrointestinal cancer from oral asbestos when rodents do not do so to a significant extent.
Considering the thalidomide disaster, this will not be the first instance in which limited use of animal models for safety assessment has led to misplaced confidence in product safety. Thalidomide, the drug given to pregnant women in Europe for morning sickness in the late 50s and early 60s, was tested in rats and found to have no adverse effects. An application to sell the drug in the US was submitted, but later withdrawn, when babies born to women taking the drug were stillborn or had severe birth defects- missing or malformed arms and legs. Decades later, it was learned that all nonhuman primate species tested except the distantly related prosimian Galago crassicaudatus are susceptible to birth defects from thalidomide (Hendrickx, 1973; Hendrickx and Newman, 1973; Hendrickx and Sawyer, 1978). Primate models are generally much closer to humans in their responses to carcinogens and toxicants, but the only report on nonhuman primates used to test oral asbestos examined baboons after 5 years or less (Webster, 1974), a latency period likely too short for asbestos-caused cancer to develop in primates.
The history of population studies on the effects of asbestos in drinking water is a virtual textbook demonstration of drawbacks to attempting to use ecologic epidemiological methods to establish the safety or danger of a suspected carcinogen.
The danger of inhaled asbestos was established relatively early because people with a known heavy exposure could be followed individually, though the latency to develop cancer from asbestos inhalation is typically 30-40 years.
In contrast, until the Norwegian lighthouse keepers were studied, inhabitants of cities with asbestos in the water supply were the only populations available for study. Unlike the lighthouse keepers, whose employment records at individual lighthouses, and hence exposure, could be individually determined, the city dwellers, for the most part, were not followed individually; they drank water with asbestos content that varied with rainfall, acidity, and their location in relation to the water system (unless they used bottled water), and, being mobile Americans, were often no longer living in the city under study after 20 to 40 years.
There must have been a great impetus to know if oral asbestos caused cancer at the time its presence in water supplies was discovered; several studies were conducted before sufficient time had passed to expect cancers to have developed (CCERP, 1987).
Even with all their drawbacks, some of the population studies did show statistically significant increases in cancer rates in association with asbestos in drinking water.
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