Sunday, September 30, 2007

leukemia cancer

Note: this is commonly mispelled as lukemia cancer, luekemia cancer, lukaemia cancer


Leukemia or leukaemia (see spelling differences) is a cancer of the blood or bone marrow and is characterized by an abnormal proliferation (production by multiplication) of blood cells, usually white blood cells (leukocytes). It is part of the broad group of diseases called hematological neoplasms.

Contents

1 Symptoms

Symptoms

Damage to the bone marrow, by way of displacing the normal bone marrow cells with higher numbers of immature white blood cells, results in a lack of blood platelets, which are important in the blood clotting process. This means people with leukemia may become bruised, bleed excessively, or develop pinprick bleeds (petechiae).

White blood cells, which are involved in fighting pathogens, may be suppressed or dysfunctional. This could cause the patient's immune system (white blood cells etc.) to start attacking other body cells.

Finally, the red blood cell deficiency leads to anemia, which may cause dyspnea. All symptoms can be attributed to other diseases; for diagnosis, blood tests and a bone marrow examination are required.

Some other related symptoms

  • Fever, chills, night sweats and other flu-like symptoms
  • Weakness and fatigue
  • Loss of appetite and/or weight
  • Swollen or bleeding gums
  • Excess bleeding (from a minor cut)
  • Neurological symptoms (headache)
  • Enlarged liver and spleen
  • Easy bruising
  • Frequent infection
  • Bone pain
  • Joint pains
  • Swollen tonsils

The word leukemia, which means 'white blood,' is derived from the disease's namesake high white blood cell counts that most leukemia patients have before treatment. The high number of white blood cells are apparent when a blood sample is viewed under a microscope. Frequently, these extra white blood cells are immature or dysfunctional. The excessive number of cells can also interfere with the normal function of other cells.

Some leukemia patients do not have high white blood cell counts visible during a regular blood count. This less-common condition is called aleukemia. The bone marrow still contains cancerous white blood cells, and they are disrupting the normal production of blood cells. However, they are staying in the marrow instead of entering the bloodstream, where they would be visible in a blood test. For an aleukemic patient, the white blood cell counts in the bloodstream can be normal or low. Aleukemia can occur in any of the four major types of leukemia, and is particularly common in hairy cell leukemia.

Four major types

Leukemia is a broad term covering a spectrum of diseases.

Leukemia is clinically and pathologically split into its acute and chronic forms.

  • Acute leukemia is characterized by the rapid proliferation of immature blood cells. This crowding makes the bone marrow unable to produce healthy blood cells. Acute forms of leukemia can occur in children and young adults. (In fact, it is a more common cause of death for children in the US than any other type of malignant disease). Immediate treatment is required in acute leukemias due to the rapid progression and accumulation of the malignant cells, which then spill over into the bloodstream and spread to other organs of the body. However, CNS involvement is uncommon, though the disease occasionally causes cranial nerve palsies.
  • Chronic leukemia is distinguished by the excessive build up of relatively mature, but still abnormal, blood cells. Typically taking months to years to progress, the cells are produced at a much higher rate than normal cells, resulting in many abnormal white blood cells in the blood. Chronic leukemia mostly occurs in older people, but can theoretically occur in any age group. Whereas acute leukemia must be treated immediately, chronic forms are sometimes monitored for some time before treatment to ensure maximum effectiveness of therapy.

Furthermore, the diseases are classified according to the type of abnormal cell found most in the blood or bone marrow (lymphoid cells vs. myeloid cells).

Combining these two classifications provides a total of four main categories:


 Acute Chronic
lymphocytic leukemia Acute lymphocytic leukemia (also known as Acute Lymphoblastic Leukemia, or ALL) is the most common type of leukemia in young children. This disease also affects adults, especially those age 65 and older. Chronic lymphocytic leukemia (CLL) most often affects adults over the age of 55. It sometimes occurs in younger adults, but it almost never affects children.
myelogenous leukemia (or "myeloid") Acute myelogenous leukemia (also known as Acute Myeloid Leukemia, or AML) occurs more commonly in adults than in children. This type of leukemia was previously called "acute nonlymphocytic leukemia". Chronic myelogenous leukemia (CML) occurs mainly in adults. A very small number of children also develop this disease.

Within these main categories, there are typically several subcategories.

Causes and risk factors

There is no single known cause for all of the different types of leukemia. The different leukemias likely have different causes, and very little is certain about what causes them. Researchers have strong suspicions about four possible causes:

  • natural or artificial ionizing radiation
  • certain kinds of chemicals
  • some viruses
  • genetic predispositions

Leukemia, like other cancers, result from somatic mutations in the DNA which activate oncogenes or deactivate tumor suppressor genes, and disrupt the regulation of cell death, differentiation or division. These mutations may occur spontaneously or as a result of exposure to radiation or carcinogenic substances and are likely to be influenced by genetic factors. Cohort and case-control studies have linked exposure to petrochemicals, such as benzene, and hair dyes to the development of some forms of leukemia.

Viruses have also been linked to some forms of leukemia. For example, certain cases of ALL are associated with viral infections by either the human immunodeficiency virus (HIV, responsible for AIDS)[citation needed] or human T-lymphotropic virus (HTLV-1 and -2, causing adult T-cell leukemia/lymphoma).

Fanconi anemia is also a risk factor for developing acute myelogenous leukemia.

Until the cause or causes of leukemia are found, there is no way to prevent the disease. Even when the causes become known, they may prove to be things which are not readily controllable, such as naturally occurring background radiation, and therefore not especially helpful for prevention purposes.

Treatment options for leukemia by type

Acute Myelogenous Leukemia (AML)

It is most common for adults; more men than women are affected. Many different chemotherapeutic plans are available for the treatment of AML. Overall, the strategy is to control bone marrow and systemic (whole-body) disease while offering specific treatment for the central nervous system (CNS), if involved. In general, most oncologists rely on combinations of drugs for the initial, induction phase of chemotherapy. Such combination chemotherapy usually offers the benefits of early remission (lessening of the disease) and a lower risk of disease resistance. Consolidation or "maintenance" treatments may be given to prevent disease recurrence once remission has been achieved. Consolidation treatment often entails a repetition of induction chemotherapy or the intensification chemotherapy with added drugs. By contrast, maintenance treatment involves drug doses that are lower than those administered during the induction phase.

In addition, specific treatment plans may be used, depending on the type of leukemia that has been diagnosed. Whatever the plan, it is important for the patient to understand the treatment that is being given and the decision-making process behind the choice.

Initial treatment of AML

Initial treatment of AML usually begins with induction chemotherapy using a combination of drugs such as daunorubicin (DNR), cytarabine (ara-C), idarubicin, thioguanine, etoposide, or mitoxantrone, anabolic steroids.

Follow-up treatment

Follow-up therapy for such patients may involve:

  • supportive care, such as intravenous nutrition and treatment with oral antibiotics (e.g., ofloxacin, rifampin), especially in patients who have prolonged granulocytopenia; that is too few mature granulocytes (neutrophils), the bacteria-destroying white blood cells that contain small particles, or granules (<>
  • injection with colony-stimulating factors such as granulocyte colony-stimulating factor (G-CSF), which may help to shorten the period of granulocytopenia that results from induction therapy
  • transfusions with red blood cells and platelets

Patients with newly diagnosed disease also may be considered for stem cell transplantation (SCT), either from the bone marrow or other sources. Allogeneic bone marrow transplant (alloBMT) is reserved primarily for patients under 55 years of age who have a compatible family donor. Approximately half of newly diagnosed AML patients are in this age group, with 75% achieving a complete remission (CR) after induction and consolidation therapy. Allogeneic bone marrow transplant is available for about 15% of all patients with AML. Unfortunately, it is estimated that only 7% of all AML patients will be cured using this procedure.

People who receive stem cell transplantation (SCT, alloBMT) require protective isolation in the hospital, including filtered air, sterile food, and sterilization of the microorganisms in the gut, until their total white blood cell (WBC) count is above 500.

Treatment of central nervous system leukemia, if present, may involve injection of chemotherapeutic drugs (e.g., cytarabine or ara-C, methotrexate) into the areas around the brain and spinal cord.

Consolidation or maintenance therapy

Once the patient is in remission, he or she will receive consolidation or maintenance therapy, for example, consolidation therapy with high-dose ara-C (HDAC) with/without anthracycline drugs).

If, however, the AML patient has resistant disease (about 15%) or relapses (about 70%), second remissions sometimes are achieved by treating them with:

  • conventional induction chemotherapy
  • high-dose ara-C (HDAC), with/without other drugs
  • etoposide or other single chemotherapeutic agents

Elderly AML patients have special treatment concerns. They may be less able to tolerate the septicemia (blood poisoning) associated with granulocytopenia, and they often have higher rates of myelodysplastic ('preleukemia') syndrome (MDS). Individuals who are over age 75 or who have significant medical conditions can be treated effectively with low-dose ara-C. High-dose post-induction chemotherapy is unlikely to be tolerated by elderly patients.

Until recently, the treatment plans and responses of children with AML did not differ much from those of adults. Yet new, more intensive induction and consolidation treatments have resulted in higher remission rates and prolonged survivals. Many induction trials have produced good results using combinations of cytarabine (ara-C) plus an anthracycline (e.g., daunorubicin, doxorubicin). In children under 3 years of age, the anthracycline used for induction should be chosen with care, since doxorubicin produces more toxicity and related deaths than daunorubicin.

Consolidation therapy is complex, but it should include at least two courses of high-dose ara-C (HDAC). Children who have hyperleukocytosis (too many white blood cells), especially monocytic M5 leukemia, have a poor prognosis.

Chronic Myelogenous Leukemia (CML)

The challenge of treating newly diagnosed CML is to determine the best overall strategy to control the disease. General strategies for management include a variety of options:

Leukapheresis, also known as a peripheral blood stem cell transplant, with stem cell cryopreservation (frozen storage) prior to any other treatment. The patient's blood is passed through a machine that removes the stem cells and then returns the blood to the patient. Leukapheresis usually takes 3 or 4 hours to complete. The stem cells may or may not be treated with drugs to kill any cancer cells. The stem cells then are stored until they are transplanted back into the patient.

HLA (human leukocyte antigen) typing of all patients under age 60, as well as typing of siblings, parents, and children, if available. This procedure will determine whether a compatible donor is available for stem cell transplantation.

Pre-treatment fertility measures (e.g., cryopreservation of semen prior to treatment; completion of a pregnancy prior to treatment) in young patients who have not completed their families.

Interferon-alpha (INF-a) therapy'.

Chemotherapy with drugs such as hydroxyurea (Hydrea®), busulfan (Myleran®) or imatinib mesylate (Gleevec(tm)).

In general, CML treatment options are divided into two groups: those that do not increase survival and those that do. Chemotherapeutic drugs such as hydroxyurea (Hydrea®) and busulfan (Myleran®) can normalize the blood count for a period of time, but they do not increase survival. They often are used to control blood counts in patients who cannot undergo SCT or who do not respond to interferon therapy because of age or medical considerations.

Gleevec, is one of a new class of cancer drugs that disables an abnormal enzyme in the cancerous cell, kills it, but leaves healthy cells virtually untouched. Other cancer therapies, such as chemotherapy, attack healthy cells as well as cancer cells, leaving patients with unpleasant and often severe side effects.

In June of 2006, the Food and Drug Administration (FDA) approved the oral tyrosine kinase inhibitor dasatinib (Sprycel(tm)) to treat CML that does not respond to other therapy.

One treatment that does impact on CML survival is allogeneic bone marrow transplantation, the use of high dose chemotherapy and radiation followed by infusion of a donor bone marrow. This procedure removes the chromosomal abnormality in a large percentage of patients and for them is curative. In addition, there is treatment with interferon (INF). About 20% to 30% of patients taking interferon show elimination of the abnormal chromosome and improved survival. Recent findings also suggest that low-dose cytarabine (ara-C), in combination with interferon, may be more beneficial than interferon alone. For patients who do not respond to interferon, autologous or allogeneic stem cell transplantation is the only alternative.

Patients with advanced-phase disease may be treated with cytotoxic drugs. For example, individuals showing myeloid transformation may be given drugs that are used to induce remission in AML - that is, daunorubicin and cytarabine, with or without 6-thioguanine or etoposide. Blast cell numbers will be reduced temporarily, but they will increase again within 3 to 6 weeks. Individuals showing lymphoid transformation have a slightly better outlook. They are treated with drugs used in the management of acute lymphocytic leukemia (ALL) - that is, prednisone, vincristine, and daunorubicin, with or without L-asparaginase.

New drugs that are being studied in clinical trials of CML include homoherringtonine with interferon-alpha (INF-a), paclitaxel (Taxol®), QS21 (a plant extract that heightens immune responses), and amifostin (a chemical that lessens some side effects of chemotherapy). In addition, clinical trials are evaluating the potential benefits of substances such as vaccines, monoclonal antibodies (immunologic substances that can direct the patient's immune system to kill cancer cells), and hormones (e.g., growth factors, interleukins).

Acute Lymphocytic Leukemia (ALL)

Proper management of ALL focuses on control of bone marrow and systemic (whole-body) disease as well as prevention of cancer at other sites, particularly the central nervous system (CNS). In general, ALL treatment is divided into several phases:

Induction chemotherapy to bring about remission - that is, leukemic cells are no longer found in bone marrow samples. For adult ALL, standard induction plans include prednisone, vincristine, and an anthracycline drug; other drug plans may include L-asparaginase or cyclophosphamide. For children with low-risk ALL, standard therapy usually consists of three drugs (prednisone, L-asparaginase, and vincristine) for the first month of treatment. High-risk children may receive these drugs plus an anthracycline such as daunorubicin.

Consolidation therapy (1-3 months in adults; 4-8 months in children) to eliminate any leukemia cells that are still "hiding" within the body. A combination of chemotherapeutic drugs is used to keep the remaining leukemia cells from developing resistance. Patients with low- to average-risk ALL receive therapy with antimetabolite drugs such as methotrexate and 6-mercaptopurine (6-MP). High-risk patients receive higher drug doses plus treatment with extra chemotherapeutic agents.

CNS prophylaxis (preventive therapy) to stop the cancer from spreading to the brain and nervous system. Standard prophylaxis may consist of:

  1. Cranial (head) irradiation plus spinal tap or intrathecal (IT) delivery (into the space around the spinal cord and brain) of the drug methotrexate.
  2. High-dose systemic and IT methotrexate, without cranial irradiation
  3. IT chemotherapy.

Only children with T-cell leukemia, a high white blood cell count, or leukemia cells in the cerebrospinal fluid (CSF) need to receive cranial irradiation as well as IT therapy.

Maintenance treatments with chemotherapeutic drugs (e.g., prednisone + vincristine + cyclophosphamide + doxorubicin; methotrexate + 6-MP) to prevent disease recurrence once remission has been achieved. Maintenance therapy usually involves drug doses that are lower than those administered during the induction phase. In children, an intensive 6-month treatment program is needed after induction, followed by 2 years of maintenance chemotherapy.

Follow-up therapy for ALL patients usually consists of:

  • supportive care, such as intravenous nutrition and treatment with oral antibiotics (e.g., ofloxacin, rifampin), especially in patients with prolonged granulocytopenia; that is, too few mature granulocytes (neutrophils), the bacteria-destroying white blood cells that contain small particles, or granules (<>
  • transfusions with red blood cells and platelets

A laboratory test known as polymerase chain reaction (PCR) is advisable for ALL patients, since it may help to identify specific genetic abnormalities. Such abnormalities have a large impact upon prognosis and, consequently, treatment plans. PCR testing is especially important for patients whose disease is B-cell in type. B-cell ALL usually is not cured by standard ALL therapy. Instead, higher response rates are achieved with the aggressive, cyclophosphamide-based regimens that are used for non-Hodgkin's lymphoma.

Among ALL patients, 3-5% children and 25-50% of adults are positive for the Philadelphia chromosome (Ph1)[citation needed]. Because these patients have a worse prognosis than other individuals with ALL, many oncologists recommend allogeneic bone marrow transplantation (alloBMT), since remission may be brief following conventional ALL chemotherapy.

People who receive bone marrow transplantation will require protective isolation in the hospital, including filtered air, sterile food, and sterilization of the microorganisms in the gut, until their total white blood cell (WBC) count is above 500.

Recurrent ALL patients usually do not benefit from additional chemotherapy alone. If possible, they should receive re-induction chemotherapy, followed by allogeneic bone marrow transplant (alloBMT).

Alternatively, patients with recurrent ALL may benefit from participation in new clinical trials of alloBMT, immune system agents, and chemotherapeutic agents, or low-dose radiotherapy, if the cancer recurs throughout the body or CNS.

Chronic Lymphocytic Leukemia (CLL)

CLL is probably incurable by present treatments. But, fortunately, a large group of CLL patients do not require therapy. Studies suggest that people with Stage A CLL (that is, individuals who have fewer than three areas of enlarged lymphoid tissue) do not benefit from early treatment. They may, in fact, suffer drawbacks because of it. Therefore, most oncologists base CLL treatment upon both the stage and symptoms of the patient.

For example, in older patients (60+ years) who have low-risk early stage disease (Rai Stage 0) a conservative "watch and wait" approach may be taken.

By contrast, older individuals with CLL-related complications or more advanced disease (Rai Stage III or IV) may benefit from chemotherapy and treatment with a corticosteroid (e.g., prednisone, prednisolone).

Corticosteroids are first-line agents for people in whom the immune systems has been altered by CLL. CLL may cause autoimmune syndromes in which the patient's immune system attacks and destroys his or her own blood cells. When the red blood cells are affected, the condition is known as immunohemolytic anemia, characterized by decreased numbers of red blood cells, which may cause fatigue, dizziness, and shortness of breath. When the blood platelets are affected, it is called immune-mediated thrombocytopenia, in which a decreased numbers of platelets may lead to bleeding.

For younger patients who are experiencing symptoms, the physician may consider early chemotherapy, plus allogeneic or autologous bone marrow transplantation (alloBMT; autoBMT).

In general, the indications for treatment are:

  • falling hemoglobin or platelet count
  • progression to a later stage of disease
  • painful, disease-related overgrowth of lymph nodes or spleen
  • lymphocyte doubling time (an indicator of lymphocyte reproduction) of fewer than 12 months

Transformation of CLL to high-grade disease or aggressive non-Hodgkin's lymphoma

If the patient experiences blood flow problems caused by high numbers of leukemia cells in the circulation, the physician may recommend leukapheresis, also known as apheresis, to separate out white blood cells, prior to chemotherapy. Symptoms that are related to enlargement of the lymph nodes in one area or an overgrown spleen may be treated by localized, low-dose radiotherapy, or surgical management by splenectomy (removal of the spleen). But if leukemia has invaded the lymph nodes at many different sites, total body irradiation (TBI) may be needed.

Chemotherapy for CLL

The chemotherapeutic plans that are used most often for CLL are:

  • combination chemotherapy with chlorambucil (Leukeran®) or cyclophosphamide (Cytoxan®) plus a corticosteroid drug such as prednisone, or
  • single-agent treatments with nucleoside drugs such as fludarabine, pentostatin, or cladribine (2-chlorodeoxyadenisine; 2-CDA). However, such drugs usually are reserved for cases in which CLL is resistant (unresponsive to treatment) or returns after chemotherapy with chlorambucil or cyclophosphamide.

People with intermediate (Rai Stage I and II) or advanced (Rai Stage III or IV) disease may be helped by participation in a clinical trial. At the present time, clinical trials are being conducted using immunologic compounds (e.g., interferons, monoclonal antibodies) as well as new chemotherapeutic agents (e.g., bryostatin, dolastatin 10, and PSC 83 - a cyclosporine drug given with chemotherapy to overcome drug resistance).

Hairy Cell Leukemia (HCL)

Hairy cell leukemia is an incurable, indolent blood disorder in which mutated, partly matured B cells accumulate in the bone marrow. Its name is derived from the shape of the cells, which look like they are covered with short, fine, hair-shaped projections. Unlike any other leukemia, HCL is characterized by low white blood cell counts.

Patients with hairy cell leukemia who are symptom-free typically do not receive immediate treatment. They engage in "watchful waiting" with routine bloodwork and exams every three to six months to monitor disease progression and identify any new symptoms.

Treatment is generally considered necessary when the patient shows signs and symptoms such as low blood cell counts (e.g., infection-fighting neutrophil count below 1.0 K/ul), frequent infections, unexplained bruises, anemia, or fatigue that is significant enough to disrupt the patient's everyday life.

Patients who need treatment, which includes most newly diagnosed HCL cases, usually receive either cladribine or pentostatin, which are both in a class of chemotherapeutic drugs known as purine analogs or nucleosides. In most cases, one round of treatment will produce a prolonged remission.

Other treatments include rituximab infusion or self-injection with Interferon-alpha. In limited cases, the patient may benefit from splenectomy (removal of the spleen). These treatments are not typically given as the first treatment for a new patient because their success rates are lower than cladribine or pentostatin.

In the short term, especially when neutrophil counts are low, an immune system hormone called granulocyte colony-stimulating factor may be taken to increase white blood cell counts. This is believed to help prevent or treat an infection. Many patients also take antibiotics until their white blood cell counts have recovered to normal levels.

Research

Significant research into the causes, diagnosis, treatment, and prognosis of leukemia is being done. Hundreds of clinical trials are being planned or conducted at any given time. Studies may focus on effective means of treatment, better ways of treating the disease, improving the quality of life for patients, or appropriate care in remission or after cure.

External links

Patient support and disease-related fundraising

Research organizations

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Bladder cancer

Note: This term is commonly misspelled as bladdr cancer, blader cancer, bldder cancer.


Bladder cancer refers to any of several types of malignant growths of the urinary bladder. It is a disease in which abnormal cells multiply without control in the bladder. The bladder is a hollow, muscular organ that stores urine; it is located in the pelvis. The most common type of bladder cancer begins in cells lining the inside of the bladder and is called urothelial cell or transitional cell carcinoma (UCC or TCC).

Contents

[hide]

Signs and symptoms

Bladder cancer characteristically causes blood in the urine, this may be visible to the naked eye (frank haematuria) or detectable only be microscope (microscopic haematuria). Other possible symptoms include pain during urination, frequent urination or feeling the need to urinate without results. These signs and symptoms are not specific to bladder cancer, and are also caused by non-cancerous conditions, including prostate infections and cystitis.

Causes

Risk factors

Exposure to environmental carcinogens of various types is responsible for the development of most bladder cancers. Tobacco use (specifically cigarette smoking) is thought to cause 50% of bladder cancers discovered in male patients and 30% of those found in female patients.[citation needed] Thirty percent of bladder tumors probably result from occupational exposure in the workplace to carcinogens such as benzidine. Occupations at risk are metal industry workers, rubber industry workers, workers in the textile industry and people who work in printing. Hairdressers are thought to be at risk as well because of their frequent exposure to permanent hair dyes. It has been proposed that hair dyes are a risk factor, and some have shown an odds ratio of 2.1 to 3.3 for risk of developing bladder cancer among women who use permanent hair dyes, while others have shown no correlation between the use of hair dyes and bladder cancer. Certain drugs such as cyclophosphamide and phenacetin are known to predispose to bladder TCC. Chronic bladder irritation (infection, bladder stones, catheters, bilharzia) predisposes to squamous cell carcinoma of the bladder. Approximately 20% of bladder cancers occur in patients without predisposing risk factors. Bladder cancer is not currently believed to be heritable (i.e., does not "run in families" as a consequence of a specific genetic abnormality).

Genetics

Like virtually all cancers, bladder cancer development involves the acquisition of mutations in various oncogenes and tumor supressor genes. Genes which may be altered in bladder cancer include FGFR3, HRAS, RB1 and TP53. Several genes have been identified which play a role in regulating the cycle of cell division, preventing cells from dividing too rapidly or in an uncontrolled way. Alterations in these genes may help explain why some bladder cancers grow and spread more rapidly than others.

A family history of bladder cancer is also a risk factor for the disease. Many cancer experts assert that some people appear to inherit reduced ability to break down certain chemicals, which makes them more sensitive to the cancer-causing effects of tobacco smoke and certain industrial chemicals.

Diagnosis

The gold standard of diagnosing bladder cancer is urine cytology and transurethral (through the urethra) cystoscopy. Urine cytology can be obtained in voided urine or at the time of the cystoscopy ("bladder washing"). Cytology is very specific (a positive result is highly indicative of bladder cancer) but suffers from low sensitivity (a negative result does not exclude the diagnosis of cancer). There are newer urine bound markers for the diagnosis of bladder cancer. These markers are more sensitive but not as specific as urine cytology. They are much more expensive as well. Many patients with a history, signs, and symptoms suspicious for bladder cancer are referred to a urologist or other physician trained in cystoscopy, a procedure in which a flexible tube bearing a camera and various instruments is intruduced into the bladder through the urethra. Suspicious lesions may be biopsied and sent for pathologic analysis.

Pathological Classification

90% of bladder cancer are transitional cell carcinomas (TCC) that arise from the inner lining of the bladder called the urothelium. The other 10% of tumours are squamous cell carcinoma, adenocarcinoma, sarcoma, small cell carcinoma and secondary deposits from cancers elsewhere in the body.

TCCs are often multifocal, with 30-40% of patients having a more than one tumour at diagnosis. The pattern of growth of TCCs can be papillary, sessile (flat) or carcinoma-in-situ (CIS).

The 1973 WHO grading system for TCCs (papilloma, G1, G2 or G3) is most commonly used despite being superseded by the 2004 WHO [1] grading (papillary neoplasm of low malignant potential (PNLMP), low grade and high grade papillary carcinoma.

CIS invariably consists of cytologically high grade tumour cells.

Bladder TCC is staged according to the 1997 TNM system:

  • Ta Non-invasive papillary tumour
  • T1 Invasive but not as far as the muscular bladder layer
  • T2 Invasive into the muscular layer
  • T3 Invasive beyond the muscle into the fat outside the bladder
  • T4 Invasive into surrounding structures like the prostate, uterus or pelvic wall

Staging

The following stages are used to classify the location, size, and spread of the cancer, according to the TNM (tumor, lymph node, and metastases) staging system:

  • Stage 0: Cancer cells are found only on the inner lining of the bladder.
  • Stage I: Cancer cells have proliferated to the layer beyond the inner lining of the urinary bladder but not to the muscles of the urinary bladder.
  • Stage II: Cancer cells have proliferated to the muscles in the bladder wall but not to the fatty tissue that surrounds the urinary bladder.
  • Stage III: Cancer cells have proliferated to the fatty tissue surrounding the urinary bladder and to the prostate gland, vagina, or uterus, but not to the lymph nodes or other organs.
  • Stage IV: Cancer cells have proliferated to the lymph nodes, pelvic or abdominal wall, and/or other organs.
  • Recurrent: Cancer has recurred in the urinary bladder or in another nearby organ after having been treated.[2]

Treatment

The treatment of bladder cancer depends on how deep the tumor invades into the bladder wall. Superficial tumors (those not entering the muscle layer) can be "shaved off" using an electrocautery device attached to a cystoscope. Immunotherapy in the form of BCG instillation is also used to treat and prevent the recurrence of superficial tumors..[3] BCG immunotherapy is effective in up to 2/3 of the cases at this stage. Instillations of chemotherapy into the bladder can also be used to treat superficial disease.

Untreated, superficial tumors may gradually begin to infiltrate the muscular wall of the bladder. Tumors that infiltrate the bladder require more radical surgery where part or all of the bladder is removed (a cystectomy) and the urinary stream is diverted. In some cases, skilled surgeons can create a substitute bladder (a neobladder) from a segment of intestinal tissue, but this largely depends upon patient preference, age of patient, renal function, and the site of the disease.

A combination of radiation and chemotherapy can also be used to treat invasive disease. It has not yet been determined how the effectiveness of this form of treatment compares to that of radical ablative surgery.

There is weak observational evidence from one very small study (84) to suggest that the concurrent use of statins is associated with failure of BCG immunotherapy.[4]

Epidemiology

In the United States, bladder cancer is the fourth most common type of cancer in men and the ninth most common cancer in women. More than 47,000 men and 16,000 women are diagnosed with bladder cancer each year. One reason for its higher incidence in men is that a molecular receptor or protein that is much more active in men than women plays a role in the development of the disease[5].

References

  1. ^ Sauter G, Algaba F, Amin MB, Busch C, Cheville J, Gasser T, Grignon D, Hofstaedter F, Lopez-Beltran A, Epstein JI. Noninvasive urothelial neoplasias: WHO classification of noninvasive papillary urothelial tumors. In World Health Organization classification of tumors. Pathology and genetics of tumors of the urinary system and male genital organs. Eble JN, Epstein JI, Sesterhenn I (eds): Lyon, IARCC Press, p. 110, 2004
  2. ^ "The Gale Encyclopedia of Cancer: A guide to Cancer and its Treatments, Second Edition. Page no. 137".
  3. ^ (1999) "BCG immunotherapy of bladder cancer: 20 years on." 353 (9165): 1689–94.
  4. ^ (2006) "Use of statins and outcome of BCG treatment for bladder cancer" 355 (25): 2705–7.
  5. ^ "Scientists Find One Reason Why Bladder Cancer Hits More Men", University of Rochester Medical Center, April 20 2007.

External links

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Thursday, September 27, 2007

Mesothelioma cancer

Note: commonly misspelled as mesotheloma cancer, mesotilioma cancer, mesotelioma cancer


Mesothelioma is a form of cancer that is almost always caused by previous exposure to asbestos.[1] In this disease, malignant cells develop in the mesothelium, a protective lining that covers most of the body's internal organs. Its most common site is the pleura (outer lining of the lungs and chest cavity), but it may also occur in the peritoneum (the lining of the abdominal cavity) or the pericardium (a sac that surrounds the heart).

Most people who develop mesothelioma have worked on jobs where they inhaled asbestos particles, or have been exposed to asbestos dust and fibre in other ways, such as by washing the clothes of a family member who worked with asbestos, or by home renovation using asbestos cement products. Unlike lung cancer, there is no association between mesothelioma and smoking [2]. In an effort to raise awareness of this form of cancer, the Meso Foundation has declared September 26th National Meso Awareness Day.

Contents

Signs and symptoms

Symptoms of mesothelioma may not appear until 20 to 50 years after exposure to asbestos. Shortness of breath, cough, and pain in the chest due to an accumulation of fluid in the pleural space are often symptoms of pleural mesothelioma.

Symptoms of peritoneal mesothelioma include weight loss and cachexia, abdominal swelling and pain due to ascites (a buildup of fluid in the abdominal cavity). Other symptoms of peritoneal mesothelioma may include bowel obstruction, blood clotting abnormalities, anemia, and fever. If the cancer has spread beyond the mesothelium to other parts of the body, symptoms may include pain, trouble swallowing, or swelling of the neck or face.

These symptoms may be caused by mesothelioma or by other, less serious conditions.

Mesothelioma that affects the pleura can cause these signs and symptoms:

  • chest wall pain
  • pleural effusion, or fluid surrounding the lung
  • shortness of breath
  • fatigue or anemia
  • wheezing, hoarseness, or cough
  • blood in the sputum (fluid) coughed up

In severe cases, the person may have many tumor masses. The individual may develop a pneumothorax, or collapse of the lung. The disease may metastasize, or spread, to other parts of the body.

Tumors that affect the abdominal cavity often do not cause symptoms until they are at a late stage. Symptoms include:

  • abdominal pain
  • ascites, or an abnormal buildup of fluid in the abdomen
  • a mass in the abdomen
  • problems with bowel function
  • weight loss

In severe cases of the disease, the following signs and symptoms may be present:

A mesothelioma does not usually spread to the bone, brain, or adrenal glands. Pleural tumors are usually found only on one side of the lungs.

Diagnosis

Diagnosing mesothelioma is often difficult, because the symptoms are similar to those of a number of other conditions. Diagnosis begins with a review of the patient's medical history. A history of exposure to asbestos may increase clinical suspicion for mesothelioma. A physical examination is performed, followed by chest X-ray and often lung function tests. The X-ray may reveal pleural thickening commonly seen after asbestos exposure and increases suspicion of mesothelioma. A CT (or CAT) scan or an MRI is usually performed. If a large amount of fluid is present, abnormal cells may be detected by cytology if this fluid is aspirated with a syringe. For pleural fluid this is done by a pleural tap or chest drain, in ascites with an paracentesis or ascitic drain and in a pericardial effusion with pericardiocentesis. While absence of malignant cells on cytology does not completely exclude mesothelioma, it makes it much more unlikely, especially if an alternative diagnosis can be made (e.g. tuberculosis, heart failure).

If cytology is positive or a plaque is regarded as suspicious, a biopsy is needed to confirm a diagnosis of mesothelioma. A doctor removes a sample of tissue for examination under a microscope by a pathologist. A biopsy may be done in different ways, depending on where the abnormal area is located. If the cancer is in the chest, the doctor may perform a thoracoscopy. In this procedure, the doctor makes a small cut through the chest wall and puts a thin, lighted tube called a thoracoscope into the chest between two ribs. Thoracoscopy allows the doctor to look inside the chest and obtain tissue samples.

If the cancer is in the abdomen, the doctor may perform a laparoscopy. To obtain tissue for examination, the doctor makes a small opening in the abdomen and inserts a special instrument into the abdominal cavity. If these procedures do not yield enough tissue, more extensive diagnostic surgery may be necessary.

Typical immunohistochemistry results
Positive Negative
EMA (epithelial membrane antigen) in a membranous distribution CEA (carcinoembryonic antigen)
WT1 (Wilms' tumour 1) B72.3
Calretinin MOC-3 1
Mesothelin-1 CD15
Cytokeratin 5/6 Ber-EP4
HBME-1 (human mesothelial cell 1) TTF-1 (thyroid transcription factor-1)

Screening

There is no universally agreed protocol for screening people who have been exposed to asbestos. However some research indicates that the serum osteopontin level might be useful in screening asbestos-exposed people for mesothelioma. The level of soluble mesothelin-related protein is elevated in the serum of about 75% of patients at diagnosis and it has been suggested that it may be useful for screening.[3]

Staging

Mesothelioma is described as localized if the cancer is found only on the membrane surface where it originated. It is classified as advanced if it has spread beyond the original membrane surface to other parts of the body, such as the lymph nodes, lungs, chest wall, or abdominal organs.

Pathophysiology

The mesothelium consists of a single layer of flattened to cuboidal cells forming the epithelial lining of the serous cavities of the body including the peritoneal, pericardial and pleural cavities. Deposition of asbestos fibres in the parenchyma of the lung may result in the penetration of the visceral pleura from where the fibre can then be carried to the pleural surface, thus leading to the development of malignant mesothelial plaques. The processes leading to the development of peritoneal mesothelioma remain unresolved, although it has been proposed that asbestos fibres from the lung are transported to the abdomen and associated organs via the lymphatic system. Additionally, asbestos fibres may be deposited in the gut after ingestion of sputum contaminated with asbestos fibres.

Pleural contamination with asbestos or other mineral fibres has been shown to cause cancer. Long thin asbestos fibers (blue asbestos, amphibole fibers) are more potent carcinogens than "feathery fibers" (chrysotile or white asbestos fibers).[4] However, there is now evidence that smaller particles may be more dangerous than the larger fibers.[1][2] They remain suspended in the air where they can be inhaled, and may penetrate more easily and deeper into the lungs. "We probably will find out a lot more about the health aspects of asbestos from [the World Trade Center attack], unfortunately," said Dr. Alan Fein, chief of pulmonary and critical-care medicine at North Shore-Long Island Jewish Health System. Dr. Fein has treated several patients for "World Trade Center syndrome" or respiratory ailments from brief exposures of only a day or two near the collapsed buildings.[3]

Mesothelioma development in rats has been demonstrated following intra-pleural inoculation of phosphorylated chrysotile fibres. It has been suggested that in humans, transport of fibres to the pleura is critical to the pathogenesis of mesothelioma. This is supported by the observed recruitment of significant numbers of macrophages and other cells of the immune system to localised lesions of accumulated asbestos fibres in the pleural and peritoneal cavities of rats. These lesions continued to attract and accumulate macrophages as the disease progressed, and cellular changes within the lesion culminated in a morphologically malignant tumour.

Experimental evidence suggests that asbestos acts as a complete carcinogen with the development of mesothelioma occurring in sequential stages of initiation and promotion. The molecular mechanisms underlying the malignant transformation of normal mesothelial cells by asbestos fibres remain unclear despite the demonstration of its oncogenic capabilities. However, complete in vitro transformation of normal human mesothelial cells to malignant phenotype following exposure to asbestos fibres has not yet been achieved. In general, asbestos fibres are thought to act through direct physical interactions with the cells of the mesothelium in conjunction with indirect effects following interaction with inflammatory cells such as macrophages.

Analysis of the interactions between asbestos fibres and DNA has shown that phagocytosed fibres are able to make contact with chromosomes, often adhering to the chromatin fibres or becoming entangled within the chromosome. This contact between the asbestos fibre and the chromosomes or structural proteins of the spindle apparatus can induce complex abnormalities. The most common abnormality is monosomy of chromosome 22. Other frequent abnormalities include structural rearrangement of 1p, 3p, 9p and 6q chromosome arms.

Common gene abnormalities in mesothelioma cell lines include deletion of the tumor suppressor genes:

Asbestos has also been shown to mediate the entry of foreign DNA into target cells. Incorporation of this foreign DNA may lead to mutations and oncogenesis by several possible mechanisms:

  • Inactivation of tumor suppressor genes
  • Activation of oncogenes
  • Activation of proto-oncogenes due to incorporation of foreign DNA containing a promoter region
  • Activation of DNA repair enzymes, which may be prone to error
  • Activation of telomerase
  • Prevention of apoptosis

Asbestos fibres have been shown to alter the function and secretory properties of macrophages, ultimately creating conditions which favour the development of mesothelioma. Following asbestos phagocytosis, macrophages generate increased amounts of hydroxyl radicals, which are normal by-products of cellular anaerobic metabolism. However, these free radicals are also known clastogenic and membrane-active agents thought to promote asbestos carcinogenicity. These oxidants can participate in the oncogenic process by directly and indirectly interacting with DNA, modifying membrane-associated cellular events, including oncogene activation and perturbation of cellular antioxidant defences.

Asbestos also may possess immunosuppressive properties. For example, chrysotile fibres have been shown to depress the in vitro proliferation of phytohemagglutinin-stimulated peripheral blood lymphocytes, suppress natural killer cell lysis and significantly reduce lymphokine-activated killer cell viability and recovery. Furthermore, genetic alterations in asbestos-activated macrophages may result in the release of potent mesothelial cell mitogens such as platelet-derived growth factor (PDGF) and transforming growth factor-β (TGF-β) which in turn, may induce the chronic stimulation and proliferation of mesothelial cells after injury by asbestos fibres.

Epidemiology

Incidence

Although reported incidence rates have increased in the past 20 years, mesothelioma is still a relatively rare cancer. The incidence is approximately one per 1,000,000. For comparison, populations with high levels of smoking can have a lung cancer incidence of over 1,000 per 1,000,000. Incidence of malignant mesothelioma currently ranges from about 7 to 40 per 1,000,000 in industrialized Western nations, depending on the amount of asbestos exposure of the populations during the past several decades.[5] It has been estimated that incidence may have peaked at 15 per 1,000,000 in the United States in 2004. Incidence is expected to continue increasing in other parts of the world. Mesothelioma occurs more often in men than in women and risk increases with age, but this disease can appear in either men or women at any age. Approximately one fifth to one third of all mesotheliomas are peritoneal.

Between 1940 and 1979, approximately 27.5 million people were occupationally exposed to asbestos in the United States [4]. Between 1973 and 1984, there has been a threefold increase in the diagnosis of pleural mesothelioma in Caucasian males. From 1980 to the late 1990s, the death rate from mesothelioma in the USA increased from 2,000 per year to 3,000, with men four times more likely to acquire it than women. These rates may not be accurate, since it is possible that many cases of mesothelioma are misdiagnosed as adenocarcinoma of the lung, which is difficult to differentiate from mesothelioma.

Risk factors

Working with asbestos is the major risk factor for mesothelioma. A history of asbestos exposure exists in almost all cases. However, mesothelioma has been reported in some individuals without any known exposure to asbestos. In rare cases, mesothelioma has also been associated with irradiation, intrapleural thorium dioxide (Thorotrast), and inhalation of other fibrous silicates, such as erionite.

Asbestos is the name of a group of minerals that occur naturally as masses of strong, flexible fibers that can be separated into thin threads and woven. Asbestos has been widely used in many industrial products, including cement, brake linings, roof shingles, flooring products, textiles, and insulation. If tiny asbestos particles float in the air, especially during the manufacturing process, they may be inhaled or swallowed, and can cause serious health problems. In addition to mesothelioma, exposure to asbestos increases the risk of lung cancer, asbestosis (a noncancerous, chronic lung ailment), and other cancers, such as those of the larynx and kidney.

The combination of smoking and asbestos exposure significantly increases a person's risk of developing cancer of the airways (lung cancer, bronchial carcinoma). The Kent brand of cigarettes used asbestos in its filters for the first few years of production in the 1950s and some cases of mesothelioma have resulted. Smoking modern cigarettes does not appear to increase the risk of mesothelioma.

Some studies suggest that simian virus 40 (SV40) may act as a cofactor in the development of mesothelioma.[6]

Exposure

Asbestos was known in antiquity, but it wasn't mined and widely used commercially until 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 publicly 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, and created guidelines for engineering controls and respirators, protective clothing, exposure monitoring, hygiene facilities and practices, warning signs, labeling, recordkeeping, and medical exams. By contrast, the British Government's Health and Safety Executive (HSE) states formally that any threshold for mesothelioma must be at a very low level and it is widely agreed that if any such threshold does exist at all, then it cannot currently be quantified. For practical purposes, therefore, HSE does not assume that any such threshold exists. People who work with asbestos wear personal protective equipment to lower their risk of exposure.

Occupational

Exposure to asbestos fibres has been recognised as an occupational health hazard since the early 1900s. Several epidemiological studies have associated exposure to asbestos with the development of lesions such as asbestos bodies in the sputum, pleural plaques, diffuse pleural thickening, asbestosis, carcinoma of the lung and larynx, gastrointestinal tumours, and diffuse mesothelioma of the pleura and peritoneum.

The documented presence of asbestos fibres in water supplies and food products has fostered concerns about the possible impact of long-term and, as yet, unknown exposure of the general population to these fibres. Although many authorities consider brief or transient exposure to asbestos fibres as inconsequential and an unlikely risk factor, some epidemiologists claim that there is no risk threshold. Cases of mesothelioma have been found in people whose only exposure was breathing the air through ventilation systems. Other cases had very minimal (3 months or less) direct exposure.

Commercial asbestos mining at Wittenoom, Western Australia, occurred between 1945 and 1966. A cohort study of miners employed at the mine reported that while no deaths occurred within the first 10 years after crocidolite exposure, 85 deaths attributable to mesothelioma had occurred by 1985. By 1994, 539 reported deaths due to mesothelioma had been reported in Western Australia.

Paraoccupational Secondary Exposure

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 fibres, asbestos workers are usually required to shower and change their clothing before leaving the workplace.

Asbestos in buildings

Many building materials used in both public and domestic premises prior to the banning of asbestos may contain asbestos. Those performing renovation works or diy activities may expose themselves to asbestos dust. In the UK use of Chrysotile asbestos was banned at the end of 1999. Brown and blue asbestos was banned in the UK around 1985. Buildings built or renovated prior to these dates may contain asbestos materials.

Environmental Exposure

Incidence of mesothelioma had been found to be higher in populations living near Naturally Occurring Asbestos (NOA).

Treatment

Treatment of MM using conventional therapies has not proved successful and patients have a median survival time of 6 - 12 months after presentation. The clinical behaviour of the malignancy is affected by several factors including the continuous mesothelial surface of the pleural cavity which favours local metastasis via exfoliated cells, invasion to underlying tissue and other organs within the pleural cavity, and the extremely long latency period between asbestos exposure and development of the disease.

Surgery

Surgery, either by itself or used in combination with pre- and post-operative adjuvant therapies has proved disappointing. A pleurectomy/decortication is the most common surgery, in which the lining of the chest is removed. Less common is an extrapleural pneumonectomy (EPP), in which the lung, lining of the inside of the chest, the hemi-diaphragm and the pericardium are removed. It is not possible to remove the entire mesothelium without killing the patient.

Radiation

Wikibooks

For patients with localized disease, and who can tolerate a radical surgery, radiation is often given post-operatively as a consolidative treatment. The entire hemi-thorax is treated with radiation therapy, often given simultaneously with chemotherapy. This approach of using surgery followed by radiation with chemotherapy has been pioneered by the thoracic oncology team at Brigham & Women's Hospital in Boston. [7] Delivering radiation and chemotherapy after a radical surgery has led to extended life expectancy in selected patient populations with some patients surviving more than 5 years. As part of a curative approach to mesothelioma, radiotherapy is also commonly applied to the sites of chest drain insertion, in order to prevent growth of the tumor along the track in the chest wall.

Although mesothelioma is generally resistant to curative treatment with radiotherapy alone, palliative treatment regimens are sometimes used to relieve symptoms arising from tumor growth, such as obstruction of a major blood vessel. Radiation therapy when given alone with curative intent has never been shown to improve survival from mesothelioma. The necessary radiation dose to treat mesothelioma that has not been surgically removed would be very toxic.

Chemotherapy

In February 2004, the United States Food and Drug Administration approved pemetrexed (brand name Alimta) for treatment of malignant pleural mesothelioma. Pemetrexed is given in combination with cisplatin. Folic acid is also used to reduce the side-effects of pemetrexed.

Immunotherapy

Treatment regimens involving immunotherapy have yielded variable results. For example, intrapleural inoculation of Bacillus Calmette-Guérin (BCG) in an attempt to boost the immune response, was found to be of no benefit to the patient (while it may benefit patients with bladder cancer). Mesothelioma cells proved susceptible to in vitro lysis by LAK cells following activation by interleukin-2 (IL-2), but patients undergoing this particular therapy experienced major side effects. Indeed, this trial was suspended in view of the unacceptably high levels of IL-2 toxicity and the severity of side effects such as fever and cachexia. Nonetheless, other trials involving interferon alpha have proved more encouraging with 20% of patients experiencing a greater than 50% reduction in tumor mass combined with minimal side effects.

Heated Intraoperative Intraperitoneal Chemotherapy

A procedure known as heated intraoperative intraperitoneal chemotherapy was developed by Paul Sugarbaker at the Washington Cancer Institute.[7] The surgeon removes as much of the tumor as possible followed by the direct administration of a chemotherapy agent, heated to between 40 and 48°C, in the abdomen. The fluid is perfused for 60 to 120 minutes and then drained.

This technique permits the administration of high concentrations of selected drugs into the abdominal and pelvic surfaces. Heating the chemotherapy treatment increases the penetration of the drugs into tissues. Also, heating itself damages the malignant cells more than the normal cells.

Prevention & Expectations

What can be done to prevent the disease? Since the 1970s, the Environmental Protection Agency and the Occupational Safety and Health Administration have regulated the asbestos industry in the U.S. In the past, asbestos was used as a fire retardant and an insulator. Other products are now used in its place. The controversy involving exposure to different forms of asbestos continues.

There are two major types of asbestos: chrysotile and amphibole. It is thought that exposure to the amphibole form is more likely to cause mesothelioma. However, chrysotile has been used more frequently, hence many mesotheliomas are caused by chrysotile.

Removal is taking place in schools and other public buildings throughout the U.S. The hope is that these measures will greatly reduce the occurrence of this cancer.

What are the long-term effects of the disease? A mesothelioma is a highly aggressive tumor that is generally deadly. Current treatment of malignant mesothelioma is designed to make the person with cancer comfortable. Although long-term survival cannot usually be expected, the case of famed paleontologist Stephen Jay Gould is a noted exception.

What are the risks to others? Mesothelioma is not contagious and cannot be passed from one person to another. The exposure to the asbestos that caused the cancer occurred many years to several decades before the disease appeared. People who live with asbestos workers have a higher risk of getting this cancer.

What happens once treatment is over? Although mesothelioma is very unpleasant it's still important for person after treatment is over to keep up all follow-up appointments and that's vital because further testing is always needed to check whether cancer is coming back or to examine possible side effects that could be rather unpleasant and what's even worse permanent.

Notable people with mesothelioma

Mesothelioma, though rare, has had a number of notable patients. Australian anti-racism activist Bob Bellear died in 2005. British science fiction writer Michael G. Coney, responsible for nearly 100 works also died in 2005. American film and television actor Paul Gleason, perhaps best known for his portrayal of Principal Richard Vernon in the 1985 film The Breakfast Club, died in 2006. Mickie Most, an English record producer, died of mesothelioma in 2003. Paul Rudolph, an American architect known for his cubist building designs, died in 1997.

Steve McQueen was diagnosed with peritoneal mesothelioma on December 22, 1979. He was not offered surgery or chemotherapy because doctors felt the cancer was too advanced. McQueen sought alternative treatments from clinics in Mexico. He died of a heart attack on November 7, 1980, in Juárez, Mexico, following cancer surgery. He may have been exposed to asbestos while serving with the US Marines as a young adult—asbestos was then commonly used to insulate ships' piping—or because of its use as an insulating material in car racing suits.[8] (It is also reported that he worked in a shipyard during World War II, where he might have been exposed to asbestos. [citation needed]

United States Congressman Bruce Vento died of mesothelioma in 2000. The Bruce Vento Hopebuilder is awarded yearly by his wife at the MARF symposium to persons or organizations who have done the most to support mesothelioma research and advocacy.

After a long period of untreated illness and pain, rock and roll musician and songwriter Warren Zevon was diagnosed with inoperable mesothelioma in the fall of 2002. Refusing treatments he believed might incapacitate him, Zevon focused his energies on recording his final album The Wind including the song Keep me in your heart which speaks of his failing breath. Zevon died at his home in Los Angeles, California, on September 7, 2003.

Although life expectancy with this disease is typically limited, there are notable survivors. In July 1982, Stephen Jay Gould was diagnosed with peritoneal mesothelioma. After his diagnosis, Gould wrote the "The Median Isn't the Message"[9] for Discover magazine, in which he argued that statistics such as median survival are just useful abstractions, not destiny. Gould lived for another twenty years eventually succumbing to metastatic adenocarcinoma of the lung, not mesothelioma.

Author Paul Kraus was diagnosed with mesothelioma in June 1997 following an umbilical hernia operation. His prognosis was "a few months." He continues to survive using a variety of integrative and complimentary modalities and has written a book about his experience.

Legal issues

Main article: asbestos and the law

The first lawsuits against asbestos manufacturers were in 1929. Since then, many lawsuits have been filed against asbestos manufacturers and employers, for neglecting to implement safety measures after the links between asbestos, asbestosis, and mesothelioma became known (some reports seem to place this as early as 1898). The liability resulting from the sheer number of lawsuits and people affected has reached billions of dollars. The amounts and method of allocating compensation have been the source of many court cases, and government attempts at resolution of existing and future cases.

History

The first lawsuit against asbestos manufacturers was brought in 1929. The parties settled that lawsuit, and as part of the agreement, the attorneys agreed not to pursue further cases. It was not until 1960 that an article published by Wagner et al first officially established mesothelioma as a disease arising from exposure to crocidolite asbestos.[10] The article referred to over 30 case studies of people who had suffered from mesothelioma in South Africa. Some exposures were transient and some were mine workers. In 1962 McNulty reported the first diagnosed case of malignant mesothelioma in an Australian asbestos worker.[11] The worker had worked in the mill at the asbestos mine in Wittenoom from 1948 to 1950.

In the town of Wittenoom, asbestos-containing mine waste was used to cover schoolyards and playgrounds. In 1965 an article in the British Journal of Industrial Medicine established that people who lived in the neighbourhoods of asbestos factories and mines, but did not work in them, had contracted mesothelioma.

Despite proof that the dust associated with asbestos mining and milling causes asbestos related disease, mining began at Wittenoom in 1943 and continued until 1966. In 1974 the first public warnings of the dangers of blue asbestos were published in a cover story called "Is this Killer in Your Home?" in Australia's Bulletin magazine. In 1978 the Western Australian Government decided to phase out the town of Wittenoom, following the publication of a Health Dept. booklet, "The Health Hazard at Wittenoom", containing the results of air sampling and an appraisal of worldwide medical information.

By 1979 the first writs for negligence related to Wittenoom were issued against CSR and its subsidiary ABA, and the Asbestos Diseases Society was formed to represent the Wittenoom victims.


References

  1. ^ United States Department of Health and Human Services.
  2. ^ "Cigarette smoking, asbestos exposure, and malignant mesothelioma" by Muscat JE, Wynder EL in Cancer Research (1991) volume 51 pages 2263-7 Entrez PubMed 2015590
  3. ^ "Soluble mesothelin-related protein--a blood test for mesothelioma" by B. W. Robinson, J. Creaney, R. Lake, A. Nowak, A. W. Musk, N. de Klerk, P. Winzell, K. E. Hellstrom and I. Hellstrom in Lung Cancer (2005) volume 49, pages S109-S111 Entrez PubMed 15950789.
  4. ^ "Malignant mesothelioma and occupational exposure to asbestos: a clinicopathological correlation of 1445 cases" by V. L. Roggli, A. Sharma, K. J. Butnor, T. Sporn and R. T. Vollmer in Ultrastruct Pathol (2002) volume 26 pages 55-65 Entrez PubMed 12036093.
  5. ^ "Advances in Malignant Mesothelioma" by Bruce W. S. Robinson and Richard A. Lake in The New England Journal of Medicine (2005) volume 353 pages 1591-1603 Entrez PubMed 16221782.
  6. ^ "SV40 in human tumors: new documents shed light on the apparent controversy" by D. S. MacLachlan in Anticancer Res (2002) volume 22, pages 3495-3499 Entrez PubMed 12552945.
  7. ^ a b "Resection margins, extrapleural nodal status, and cell type determine postoperative long-term survival in trimodality therapy of malignant pleural mesothelioma: results in 183 patients." by D. Sugarbaker in J Thorac Cardiovasc Surg (1999) volume 117, pages 54-63 Entrez PubMed 9869758.
  8. ^ McQueen's Legacy of Laetrile. New York Times (2005-11-15).
  9. ^ Gould, Stephen Jay. The Median Isn't the Message.
  10. ^ "Diffuse pleural mesothelioma and asbestos exposure in the North Western Cape Province" by J. C. Wagner, C. A. Sleggs and P. Marchand in Br J Ind Med. (1960) volume 17, pages 260-271 Entrez PubMed 13782506.
  11. ^ "Malignant pleural mesothelioma in an asbestos worker" by J. C. McNulty in Med J Aust (1962) volume 49, pages 953-954 Entrez PubMed 13932248.

See also

External links

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