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  1. Overview-Hodgkin's disease
  2. Risk Factors
  3. Recognizing Symptoms
  4. Diagnosis
  5. Classification & Staging
  6. Orthodox Treatment
  7. Side Effects of Orthodox Treatment

Overview

Hodgkin's disease is a cancer that originates in the nodes of the lymphatic system, the collection of organs, tissues, and vessels that produce infection-fighting cells and carries them throughout the body.

Hodgkin's disease can occur throughout life but is most common in early adulthood (ages 15 to 40, peaking in people between 25 and 30). The rate at which new cases are diagnosed has remained stable over the past five decades, while death rates have fallen more than 60 percent since the early 1970s because of advances in treatment. The majority of patients with Hodgkin's disease can be cured with current therapy.

The organs and tissues that make up the lymphatic system include the lymph nodes, thymus, spleen, tonsils and adenoids, bone marrow, and tissues in the gastrointestinal tract. Lymph (fluid from these tissues) contains proteins, immune cells, and waste products, and travels throughout the body in the vessels of this system. The lymph nodes (small bean-shaped organs in the neck, groin, underarms, and inside the pelvis, abdomen, and chest) produce and store white blood cells called lymphocytes, as do other lymphatic tissues. There are three kinds of lymphocytes: B lymphocytes (or B cells), T lymphocytes (or T cells), and natural killer (NK) cells. Each of these types of cells performs a unique job in the battle against infectious agents, targeting a very particular range of pathogens.


Hodgkin's disease arises when one of these cells (most often a B cell) undergoes a transformation from a normal cell into a malignant cell, one capable of uncontrolled growth and spread. The malignant cell begins producing identical copies of itself, or clones, in the lymph nodes. Over time these malignant cells can spread to neighboring groups of lymph nodes, and if not treated, may spread to other parts of the body. In Hodgkin's disease, the tumors spread from lymph node group to lymph node group via the lymphatic vessels. The most common site of involvement is the lymph nodes in the chest; this region is called the mediastinum.
Physicians distinguish Hodgkin's disease from other types of lymphoma, in part, by examining tissue samples under a microscope; biopsied tissue from patients with Hodgkin's disease includes a certain number of cells called Reed-Sternberg cells (named after the two physicians who first described them). These cells are bigger than normal cells and have large, pale nuclei (the site in each cell where chromosomes -- genetic material -- are located). Researchers have recently discovered that Reed-Sternberg cells almost always originate from B cells.

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Risk Factors

Risk factors for different types of cancer are those traits that increase the likelihood that an individual will develop disease. Risk factors include certain kinds of behavior such as smoking, inherited (genetic) traits, and exposure to cancer-causing agents in the environment. There is only a very small chance that a person who has one of the few known risk factors for Hodgkin's disease will develop the disease.

People whose immune systems are compromised -- as a result of inherited genetic diseases, HIV infection, or administration of immunosuppressive drugs as after an organ transplant -- have a slightly higher than average risk of developing Hodgkin's disease. New research shows that viruses and bacteria may play a role in initiating the disease. In about half of patients with Hodgkin's disease the tumors can be shown to express proteins associated with the Epstein-Barr virus.

Members of families in which one or more people have been diagnosed with Hodgkin's disease also have a slightly higher than average risk of developing the disease.

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Recognizing Symptoms

Hodgkin's disease can arise in lymph nodes almost anywhere in the body, and symptoms of the disease depend on its location. If Hodgkin's disease develops in lymph nodes that are close to the skin in the neck, underarms, and groin, symptoms are likely to include a persistent, painless swelling of the nodes. If the disease develops in the chest, symptoms may include cough, shortness of breath, and chest pain. When Hodgkin's disease involves lymph nodes in the pelvis or abdomen, symptoms may include a feeling of fullness or abdominal swelling.

Lymph nodes swell for many reasons, most often as a result of an infection; swollen lymph nodes are usually not caused by Hodgkin's disease. Physicians may treat a patient who has a persistent swelling with antibiotics. If this treatment does not reduce the swelling, the physician may order a biopsy of the swollen node.

Other generalized symptoms of Hodgkin's disease include fever, fatigue, night sweats, unexpected weight loss, and itchy skin. A rare but almost diagnostic symptom is pain induced by the ingestion of alcohol. Like swollen lymph nodes, these symptoms (except for the last) are associated with a wide range of conditions and illnesses. But if these problems persist, consult a physician.

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Diagnosis

Physicians use several kinds of tests to diagnose Hodgkin's disease. These tests help determine the patient's exact type of Hodgkin's disease and uncover other features that are helpful in deciding on the most effective course of treatment.

During a biopsy, physicians remove a small amount of tissue for analysis. There are several types of biopsies, including:

Excisional or incisional biopsy, in which the physician cuts through the skin to remove an entire node (excisional) or a small amount of tumor tissue (incisional). This is considered the gold standard for the diagnosis of Hodgkin's disease.

Bone marrow aspiration, in which the physician withdraws a small sample of bone marrow through a syringe. This test is unlikely to result in a new diagnosis of Hodgkin's disease, but it can help determine the extent of the spread of Hodgkin's disease.

Physicians use imaging tests to determine the location of tumors in the body. Chest x-rays can detect tumors in the chest and lungs. Using computed tomography (CT scan), physicians can take pictures of the body from a number of angles; these pictures are then combined to produce detailed images of the inside of the body. Magnetic resonance imaging (MRI) uses magnets and radio waves to produce detailed pictures of soft tissue and organs. In gallium scans and positron emission tomography scans using fluorodeoxyglucose (FDG-PET), a radioactive substance is injected into the body and attracted to cancerous sites in the body. Using a special camera, physicians can see where the radioactive material migrated, and determine the extent of the spread of Hodgkin's disease.

In addition, physicians can use a number of tests that help them determine specific features of the cells in biopsied tissue including genetic abnormalities such as chromosomal rearrangements -- which are common in lymphomas -- and whether the cells have receptors for specific antigens (which helps both identify the cells' origins and determine the patient's prognosis). These tests include:

cytogenetic studies to determine chromosome changes in cells

immunohistochemistry studies, in which antibodies are used to distinguish between types of cancer cells

flow cytometry, in which prepared cells are passed through a laser beam for analysis

molecular genetic studies (highly sensitive DNA and RNA tests to determine specific genetic traits of cancer cells)

New diagnostic tests and procedures are emerging from work on the human genome and gene expression analysis; these are likely to be important in the future but are currently experimental.

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Classification & Staging

When diagnosing Hodgkin's disease, physicians classify the patient's disease (determine its type) and stage the disease (discover if and how far it has spread from its site of origin). This information is crucial in selecting a treatment and delineating the patient's prognosis, or outlook.

Classification
The systems physicians have used to classify Hodgkin's disease have evolved as understanding of the disease has progressed. The current system is the WHO/REAL system (for World Health Organization/Revised European American Lymphoma classification). Under this system, lymphomas are divided according to a number of characteristics: the appearance of the cells, their genetic features, their chemistry, and their clinical behavior.

The WHO/REAL system describes two main types of Hodgkin's disease:

Nodular lymphocyte-predominant Hodgkin's lymphoma, which accounts for 5 percent of cases of Hodgkin's disease
Classical Hodgkin's lymphoma, which accounts for 95 percent of cases

In nodular lymphocyte-predominant Hodgkin's disease, which affects more men than women, the lymph nodes contain mostly reactive lymphocytes and malignant B cells called popcorn cells or lacunar cells.
Classical Hodgkin's disease is further divided into three subtypes:

Nodular sclerosis Hodgkin's lymphoma: In this form of the disease, which accounts for 70 to 80 percent of cases, the lymph nodes usually contain scar tissue (sclerosis), normal and reactive lymphocytes, and Reed-Sternberg cells.

Mixed cellularity Hodgkin's lymphoma: In this form of the disease, which accounts for 20 percent of cases, the lymph nodes contain Reed-Sternberg and inflammatory cells, and sclerosis is absent.

Lymphocyte depletion Hodgkin's lymphoma: There are two types of this form of the disease, one with layers of malignant cells, the other with few Reed-Sternberg cells and lymphocytes. In recent years, the incidence of this form has declined for reasons that are not clear.
Classical and nodular lymphocyte-predominant Hodgkin's disease each have particular genetic and clinical features that distinguish them from each other. The cells of each type of disease display different, particular antigen receptors on their surfaces. Classical Hodgkin's disease is commonly distributed along the mediastinum (the space in the chest cavity behind the sternum and in between the two sacs that contain the lungs) and a late relapse following treatment is rare. In patients with nodular lymphocyte-predominant Hodgkin's lymphoma, the disease is more commonly found in the lymph nodes in peripheral sites such as the neck or under the arm; the disease usually progresses slowly, and late relapses are not uncommon but patients generally fare well despite these relapses.

Staging
Once physicians have gathered all the information available from diagnostic tests, they will stage the disease, or determine the extent of its spread. Physicians stage Hodgkin's disease as follows, using the Modified Ann Arbor Staging system.

Stage I: Disease is limited to one site or group of lymph nodes.

Stage II: Disease is found in more than one site, but is limited to one side of the diaphragm.

Stage III: Disease is found in lymph nodes both above and below the diaphragm.

Stage IV: Disease has spread outside the lymph nodes to other organs (for example, lung, liver, bone marrow).

Staging can be further modified according to the absence or presence of so-called B symptoms. Although Hodgkin's disease responds better to treatment when diagnosed early, patients with one or more of the following factors tend to have poorer outcomes than patients without these factors:

B symptoms: Fever higher than 100.5, drenching night sweats, and loss of more than 10 percent of the patient's baseline body weight.

Bulky disease: A tumor larger than 10 centimeters.

Disease found in more than four sites.


If the stage includes the letter B (e.g., stage IIIB), B symptoms are present; if it includes the letter A, those symptoms are absent. Stages I and II, and IIIA are considered early-stage disease. Stages IIIB and IV are considered advanced-stage disease.

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Orthodox Treatment

Physicians generally treat classical Hodgkin's lymphoma with combined chemotherapy and radiotherapy, and nodular lymphocyte-predominant Hodgkin's lymphoma with involved-field radiotherapy -- radiation limited to the area where disease is detected.

For early-stage disease of both types, physicians are working to reduce both the size of the area exposed to radiation and the dose of radiation; to avoid chemotherapy that may lead to late complications; and to combine fewer cycles of more effective and less toxic agents such as ABVD (doxorubicin [Adriamycin], bleomycin, vinblastine, and dacarbazine) with reduced radiotherapy.

For advanced-stage disease, the standard of care is combination chemotherapy: ABVD or Stanford V (an intensive, short-course, seven-drug regimen). The role of radiotherapy combined with ABVD is still controversial; current studies indicate that additional radiotherapy reduces relapse rates but does not improve overall survival. Stanford V is most often administered as a combination program with chemotherapy followed by radiation therapy.

For patients whose disease recurs, physicians choose different approaches depending on the nature of the initial treatment. For those who relapse after radiotherapy alone, treatment with standard-dose chemotherapy has a high rate of success. For patients whose relapse follows chemotherapy or a combination of treatment modalities, treatment could include stem cell transplantation.

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Side Effects of Orthodox Treatment

As early as 1902, physicians used radiotherapy to treat Hodgkin's disease, and investigators developed chemotherapeutic regimens for the disease in the mid-1960s. These decades of experience have allowed researchers to observe and understand the later complications of various treatment approaches.

High-dose radiation and toxic chemotherapeutic regimens such as MOPP (mechlorethamine, vincristine [Oncovin], procarbazine, and prednisone) and etoposide have been linked to second tumors -- solid tumors including breast, lung, cancer, thyroid, and skin cancers, as well as hematologic cancers such as non-Hodgkin's lymphoma and leukemia. Patients may also experience cardiac complications such as coronary heart disease after high-dose radiotherapy. Following treatment -- and throughout their lives -- people who have had Hodgkin's disease should make sure that their physicians carefully monitor them for any of these complications of treatment.

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