LYMPHEDEMA AND MELANOMA
Arm or Leg Swelling and Melanoma
Key Terms and Related Words: Melanoma, lymphedema, edema, leg swelling, arm swelling, lymph node, biopsy, lymph node dissection, radiation therapy, cutaneous melanoma, skin cancer, inguinal node, axillary lymph node biopsy, sentinel node biopsy,===================
Arm and Leg Swelling After Melanoma
With the advent of better and more effective cancer treatments, the survival rate for all cancers has risen dramatically. With this progress, a new and often misunderstood and misdiagnosed complication has arisen.
What is Melanoma?
The Skin Cancer Foundation states that "melanoma is The most dangerous form of skin cancer, these cancerous growths develop when unrepaired DNA damage to skin cells (most often caused by ultraviolet radiation from sunshine or tanning beds) triggers mutations (genetic defects) that lead the skin cells to multiply rapidly and form malignant tumors. These tumors originate in the pigment-producing melanocytes in the basal layer of the epidermis. Melanomas often resemble moles; some develop from moles. The majority of melanomas are black or brown, but they can also be skin-colored, pink, red, purple, blue or white. Melanoma is caused mainly by intense, occasional UV exposure (frequently leading to sunburn), especially in those who are genetically predisposed to the disease. Melanoma kills an estimated 8,790 people in the US annually. "
The foundation also says, "Melanoma poses an increasingly difficult problem as more people are affected. The incidence is estimated to be rising by almost 6% per year. Recognition of this disease as an entity is crucial so that people may seek medical attention while the tumor is still in its early stages, prior to metastasis. Efforts should be directed toward public awareness campaigns."
Despite that, as diagnoses and treatment have improved, the survival ratio of melanoma has steadily increased.Many cancer survivors (of all types of cancer), having overcome cancer, find themselves with sudden and often unexplained swelling, usually of the arms or of the legs. This has been true for melanoma patients as well. Since this is one of the fastest growing cancers, it is important for patients to fullly informed about not only the disease itself, but potential complications like lymphedema. Lymphedema shows up in its early stages as a slight swelling.
This swelling occurs because of several factors.
First, the swelling begins after lymph nodes have been removed for cancer biopsies.
Second, the swelling may start as a result of radiation damage to either the lymph nodes and/or the lymph system.
Due to either the removal of lymph nodes or damage to the lymph system, your body is no longer able to rid itself of excess fluids. The fluids collect in the limbs effected and swelling beings.
This swelling is called lymphedema. The swelling that occurs is permanent, and while it is not curable it is treatable.
Permanent Arm or Leg Swelling
****In the situation of any permanent leg or arm swelling whether the cause is known or unknown, the diagnoses of lymphedema must be considered****
There are several groups of people who experience leg and/or arm swelling from known causes, but it doesn't go away or unknown causes where the swelling can actually get worse as time goes by.
This group includes those who have had the injuries, infections, insect bites, trauma to the leg, surgeries or reaction to a medication. When this swelling does not go away, and becomes permanent it is called secondary lymphedema.
Another extremely large group that experiences permanent leg or arm swelling are cancer patients, people who are morbidly obese, or those with the condition called lepedema. What causes the swelling to remain permanent is that the lymph system has been so damaged that it can no longer operate normally in removing the body's waste fluid.
In cancer patients this is the result of either removal of the lymph nodes for cancer biopsy, radiation damage to the lymph system, or damage from tumor/cancer surgeries.
This is also referred to as secondary lymphedema.
Group three consists of people who have leg swelling from seemingly unknown reasons. There may be no injury, no cancer, no trauma, but for some reason the leg simply is swollen all the time.
The swelling may start at birth, it may begin at puberty, or may begin in the 3rd, 4th or even 5th decade of life or sometimes later.
This type of leg swelling is called primary lymphedema. It can be caused by a genetic defect, malformation or damage to the lymph system while in the womb or at birth or be part of another birth condition that also effects the lymph system.
This is an extremely serious medical condition that must be diagnosed early, and treated quickly so as to avoid painful, debilitating and even life threatening complications. Treatment should NOT include the use of diuretics.
What is Lymphedema?
Lymphedema is defined simply as an accumulation of excessive protein rich fluid in the tissues of the leg. The accumulation of fluid causes the permanent swelling caused by a defective lymph system.
A conservative estimate is that there may be 1-2 million people in the United States with some form of primary lymphedema and two to three million with secondary lymphedema.
What are the symptoms of Lymphedema?
IIf you are an at risk person for arm or leg lymphedema there are early warning signs you should be aware of. If you experience any or several of these symptoms, you should immediately make your physician aware of them.
1.) Unexplained aching, hurting or pain in the arm or leg
2.) Experiencing "fleeting lymphedema." This is where the limb may swell, even slightly, then return to normal. This may be a precursor to full blown arm lymphedema.
3.) Localized swelling of any area. Sometimes lymphedema may start as swelling in one area, for example the hand, or between the elbow and hand. This is an indication of early lymphatic malfunction.
4.) Any arm inflammation, redness or infection.
5.) You may experience a feeling of tightness, heaviness or weakness of the arm or leg.
How is Lymphedema Treated?
The preferred treatment today is decongestive therapy. The forms of therapy are complete decongestive therapy (CDT) or manual decongestive therapy (MDT), there are variances, but most involve these two type of treatment.
It is a form of massage therapy where the leg is very gently massaged to actually move the fluid out of the leg and into an area where the lymph system still functions normally.
With these massage treatments, swelling is reduced and then the patient is fitted with a pre-measured custom pressure garment to keep the swelling down and/or is taught to use compression wraps to maintain the leg size.
What are some of the complications of lymphedema?
Infections such as cellulitis,
lymphangitis, erysipelas. This is due not only to the large
fluid, but it is well documented that lymphodemous limbs are localized
2. Draining wounds that leak lymphorrea which is very caustic to surrounding skin tissue and acts as a port of entry for infections.
3. Increased pain as a result of the compression of nerves usually caused by the development of fibrosis and increased build up of fluids.
4. Loss of Function due to the swelling and limb changes.
5. Depression - Psychological coping as a result of the disfigurement and debilitating effect of lymphedema.
6. Deep venous thrombosis again as a result of the pressure of the swelling and fibrosis against the vascular system. Also, can happen as a result of cellulitis, lymphangitis and infections.
7. Sepsis, Gangrene are possibilities as a result of the infections.
8. Possible amputation of the limb.
9. Pleural effusions may result if the lymphatics in the abdomen or chest are to overwhelmed to clear the lung cavity of fluids.
10. Skin complications such as splitting, plaques, susceptibility to fungus and bacterial infections.
11. Chronic localized inflammations.
Can lymphedema be cured?
No, at the present time there is no cure for lymphedema. But it can be treated and managed and most of the compilcations can be avoided. Life with lymphedema can still be active and full, with proper treatment, patient education, and patient life style adaptation.
For extensive information on lymphedema, please visit our home page:
(c) Copyright 2005 by Pat O'Connor and Lymphedema People. Use of this information for educational purpose is encouraged and permitted. It must be available free and without charge and not used for financial renumeration or gain. Please include an acknowledgement to the author and a link to Lymphedema People.
|LYMPHEDEMA AFTER COMPLETE NODE DISSECTION:
Lymphedema After Complete Axillary Node Dissection for Melanoma: Assessment Using a New, Objective Definition.
Starritt, Emma C. MBBS, PhD *; Joseph, David MBBS *; McKinnon, J Gregory MD *; Lo, Sing Kai PhD +; de Wilt, Johannes H. W. MD *; Thompson, John F. MD *++
Objectives: The objectives of this study were to define appropriate criteria for assessing the presence of lymphedema, and to report the prevalence and risk factors for development of upper limb lymphedema after level I-III axillary dissection for melanoma.
Summary Background Data: The lack of a consistent and reliable objective definition for lymphedema remains a significant barrier to appreciating its prevalence after axillary dissection for melanoma (or breast carcinoma).
Methods: Lymphedema was assessed in 107 patients (82 male, 25 female) who had previously undergone complete level I-III axillary dissection. Of the 107 patients, 17 had also received postoperative axillary radiotherapy. Arm volume was measured using a water displacement technique.
Change in volume of the arm on the side of the dissection was referenced to the volume of the other (control) arm. Volume measurements were corrected for the effect of handedness using corrections derived from a control group.
Classification and regression tree (CART) analysis was used to determine a threshold fractional arm volume increase above which volume changes were considered to indicate lymphedema.
Results: Based on the CART analysis results, lymphedema was defined as an increase in arm volume greater than 16% of the volume of the control arm.
Using this definition, lymphedema prevalence for patients in the present study was 10% after complete level I-III axillary dissection for melanoma and 53% after additional axillary radiotherapy. Radiotherapy and wound complications were independent risk factors for the development of lymphedema.
Conclusions: A suggested objective definition for arm lymphedema after axillary dissection is an arm volume increase of greater than 16% of the volume of the control arm.
Annals of Surgery. 240(5):866-874, November 2004.
This FAQ was written as a public service, and is intended as an educational aid. Nothing herein should be construed as medical advice.
Melanoma is a
type of cancer, originating in the melanocytes, the cells
containing color. Approximately 47,700 cases per year are currently
the United States alone, and the incidence is increasing at the rate of
year, one of the fastest increases in occurence rates of all cancers.
2% of occurences, the disease is present even though no skin
occurs. This is called amelanotic melanoma.
The American Cancer Society estimates that there are currently 480,000 cases of melanoma in America today and that there are 7,700 deaths per year from the disease. In the U.S., Europe and Australia there are 90,000 new cases diagnosed per year and 15,000 deaths annually.
"According to the American Academy of Dermatology, one person dies from malignant melanoma every hour. The overall incidence rate for the disease is increasing faster than that of any other cancer and by the year 2000, an American's lifetime risk of developing melanoma will be one in 75. The disease is now the most commonly occurring cancer in women between the ages of 25 and 29 -- and is second only to breast cancer in women ages 30 to 34. " - Sept. 24, 1996 /PRNewswire; SOURCE: Schering-Plough Corporation.
When melanoma spreads, it often affects other places on the skin, lymph nodes, lungs, liver, brain or bones. Such secondary spread is referred to as Metastatic Melanoma..
Many cancer patients prefer not to dwell on the statistical survival rates, preferring to recognize that each person's case is quite different and unique; many factors can help a person survive, and positive thinking is considered to be one of those factors. There are many people who have been living productive lives for many years after being diagn
1) What is a Melanoma?
Melanoma is the malignant tumor deriving from melanocytes through malignant transformation. Melanocytes are derivative cells originating from the neuro-ectodermal crest (the tissue matrix for the brain and medullary spine), which do migrate during the early fetal period into the skin, where they settle within the epidermis and become part of the complex skin structure. These cells are by no means skin cells as they have a neuro-ectodermal origin, the potential of migrating, and the functional capacity of nerve cell units: One of the most prominent functional features of melanocytes is to produce the melanin pigment as a response to UV radiation in order to protect the skin structures from sunburn damage.
2) Where are melanocytes locacted in the skin?
The Melanocytes are scattered singularly through the basal parts of the epidermis. Sometimes, they form cell clusters at the rete edges, which are clinically visible and known as "melanocytic nevi". These nevi are regularly benign and should no be mixed up with melanomas. However, as they contain melanocytes, these melanocytes might become malignant as is the case with melanocytes outside of nevi.
a): The malignant tumor deriving from keratinocytes is termed "squamous cell carcinoma".
b) The malignant tumor deriving from basal keratinocytes is termed "basal cell carcinoma".
3) What are Stages?
Melanoma is most commonly classified in four Stages, determined by how deeply the cancer cells have penetrated the body. Stage I involves a mole or growth on the top layer of the skin. Stage II indicates that the growth is deeper but has not spread anywhere else in the body. Stage III is when the melanoma has spread to a nearby lymph basin (the most common) or other nearby tissues. Stage IV melanoma has spread to other more distant areas of the body. As you would logically assume, Stage I is less dangerous and easier to treat, and each higher stage is progressively more serious.
Other systems of staging are also used by some doctors. Ask your doctor about the definitions of staging he or she may use.
4) What are the recommended treatments for melanoma?
Surgery is the most common treatment for melanoma, especially for Stages I through III. About 95% of melanoma cases are treated first with surgery. Other treatments are also added as needed, and include chemotherapy, immunotherapy, radiation therapy, or a combination of the three. As an example of how they are sometimes used together, one of the MEL-L members received an intensive therapy involving 3 days of DTIC and cisplatin, followed by 8 days of Interleukin-2 and Interferon per month. This treatment regimen had severe (but temporary) side effects, including nausea, dry heaves, exhaustion, shortness of breath.
Chemotherapy can either be a systemic treatment, affecting cancer cells all over the body, or it can be applied using localized techniques called infusion and perfusion, where chemicals are placed into the limb or area where melanoma presented itself..
Immunotherapy (also known as biological therapy) is designed to help the immune system to fight off the cancer cells. Interferon and Interleukin are common forms of immunotherapy for melanoma. Interferon, a substance naturally produced in the body, works to boost the body's immune reaction to cancer cells, and also may inhibit the growth of these cells, or help them to act more normally in the body. Interleukin stimulates the growth of white blood cells, a major asset to the immune system.
Another form of immunotherapy is vaccine therapy, of which there are several kinds. All vaccine therapies are considered experimental and unproven by most cancer experts at the time of writing, yet are also very promising. Autologous vaccine is that in which the patient's own tumor cells are made into a vaccine that will cause the patient's body to make antibodies against melanoma. The vaccine used at the John Wayne Cancer Institute is created from three different lab-cultured cell lines (originally other patient's tumor specimens). Each of these cell lines were specifically selected because they exhibit many antigens (surface markers) which the immune system uses to identify unwanted cells. The widest variety of antigens helps teach the immune system to identify and destroy most of the various cell mutations.
Live vs. dead
cell vaccines: JWCI's vaccine is a live cell vaccine in which
the laboratory cells are irradiated so they cannot survive; the
not inhibit their ability to stimulate the patient's immune response.
vaccines use various cell sources and destroy them via a blender-like
Sometimes these cell fragments are mixed with known immune response
like BCG (bovine tuberculosis), interferon-alpha, or one of the many
The following quote comes from an unattributed news article about melanoma vaccine from the internet: "Melanoma vaccines are designed to rev up the immune response to renegade cells. The vaccines contain antigens--molecules found on the surface of tumor cells--modified to look more dangerous to the immune system. Which tumor antigens are most likely to elicit a strong immune response against melanoma cells is a matter of debate.
"At Memorial Sloan-Kettering Cancer Center in New York, Philip Livingston is using a single antigen that is more common on melanoma cells than on normal cells. One drawback is that a particular antigen might not be present on all patients' tumor cells. Even if it is, it might not play a key role, so knocking it out might not kill the cells.
"To ensure that a vaccine includes tumor antigens from a specific patient,researchers like David Berd at Thomas Jefferson University in Philadelphia are using melanoma cells removed from each patient being treated. This method is more labor-intensive than utilizing an off-the-shelf vaccine. A middle-of-the-road approach, taken by Jean-Claude Bystryn at New York University, Malcolm Mitchell at the University of California at San Diego and others, combines three or four melanoma cell lines thought to contain nearly all possible antigens."
Radiation therapy damages the cancer cells, inhibiting their growth. It is a localized treatment, not usually used alone for melanoma, but sometimes used in conjunction as an adjuvant treatment when the patient has additional types of cancer along with melanoma.
therapy is any of the above treatments given after surgery in the
hope of preventing melanoma from recurring, and are usually only given
patients with Stages II, III, & IV.
The recent findings with Interferon probably make it the preferred standard adjuvant treatment option available today, although there are many supporters of Interleukin and vaccine as well.
Many experimental protocols are in the works, and new ones may be introduced at any time. For example, a Tyrosinase Specific T-cell study at Fred Hutchinson/University of Washington shows promise. You will need to research the latest information, both when you first start to learn about your illness and periodically thereafter.
The key to survival often seems to be to treat melanoma in the early stages, so it might not be wise to wait for reccurrence before commencing some form of adjuvant treatment. Most protocols last about one year.
treatments are controversial, and all have their supporters,
melanoma patients should research all the above therapies as thoroughly
can before making decisions. Among other things, be sure to ask your
explain both the track record of the treatment, and how long the
results tend to
last. This is doubly important because research suggests that patients
"take charge" of their healing, rather than accepting their doctor's
advice passively, have better survival rates. Seek out the best
since many times you will not get a second chance. And get a second
melanoma can be very aggressive, so another opinion is warranted. It
been suggested that significant improvements in survival rates occur
patients participate actively in a support group for people with cancer.
Try to understand the theory behind the therapy you are taking. A "whatever you say, doctor" attitude will do nothing to help you combat the disease. Most importantly, remember, doctors are human beings and don't have the magic cure for all of us, so although you may trust yours implicitly, their are others which may offer something with more benefit.
Because of the chance of recurrence, all melanoma patients should be examined regularly by a dermatologist or other physician with experience in diagnosing melanoma, and should also examine their own skin often. The experience level of the practioner is very important.
NOTE: Many specialists recommend that siblings and children of all melanoma patients also be examined by a dermatologist regularly, since there appears to be a genetic link.
6) Where can I find melanoma information offline?
The National Cancer Institute at 800-4-CANCER offers packages of information about each stage of melanoma. They also can provide a list of active trials of new therapies.
7) What about alternative therapies?
are investigating cancer treatments outside of the standard
medical approach. If you are interested in learning more about
medicine for cancer, a clearing house for information is:
The Center For Advancement In Cancer Education
300 E. Lancaster Avenue
Wynnewood, PA 19096
Institute has been helping cancer patients with diet and lifestyle
changes for twenty five years. They have a world-wide network of
macrobiotic counselors. Get a referral and more information from:
The Kushi Institute
PO Box 7
Becket, MA 01223-0007
8) Are there any medications I should avoid if I am diagnosed with melanoma?
Some melanoma cells are dependent on estrogen for growth. Check with your doctor to assess the risk to you if you are on estrogen therapy, or taking any other hormones.
9) What is lymphedema?
After surgery, radiation, or chemotherapy to one or more lymph nodes, a secondary problem sometimes arises called lymphedema. The lymphatic fluids that would normally drain to the node are no longer being served by it, and begin to collect in the nearby tissues, causing swelling.
naturally, is much less serious than cancer, and sometimes the
doctor may not think to mention it. Nonetheless, it is extremely
manage lymphedema properly, and learn about self-care. The more serious
concerns caused by lymphedema are infections and fibrosis in the
In addition, lymphedema can affect your mobility, it's uncomfortable,
looks unattractive. If untreated, it can become worse over time. Your
refer you to a physical therapist who specializes in lymphedema. Or get
referral and further information from:
National Lymphedema Network
2211 Post St #404
San Francisco, CA 94115-3427
10) Where can I receive treatment using vaccine therapy?
Some of the
better known clinics or hospitals conducting research and trials
into melanoma vaccines are the following:
* John Wayne Cancer Institute, Santa Monica, CA (Dr. D.L. Morton)
* University of Texas: M.D. Anderson Cancer Center, Houston, TX (Dr. S. Lehga)
* Scripps Clinic, La Jolla, CA (Dr. Malcolm Mitchell)
* Memorial Sloan-Kettering Hospital, New York, NY (Dr. P. Livingston)
* Thomas Jefferson Hospital, Philadelphia, PA (Dr. David Berd)
11) What is a sentinel lymph node biopsy?
A lymphoscintography, also known as gamma directed sentinel node detection, is a way to detect the primary lymph node into which drainage would occur, so that fewer lymph nodes need to be removed for biopsy. The detected lymph node is then removed and biopsied.
12) Is it true that melanoma patients should not take Vitamin C supplements?
The chief imunologist's office at Sloan-Kettering recommends that their patients not take vitamin C. They said this in an unpublished report based on findings in their lab that Vitamin C accelerates melanoma. Vitamin C provides a channel for melanin and for the amino-acid, tyrosine. Tyrosine is under suspicion as a "bad guy" in melanoma. Other major cancer centers, including JWCI, see no problem with Vitamin C.
13) What are the side effects of treatments?
The vaccines generally don't have significant side effects. Interferon can cause discomfort for some people, while others notice little effect. Combinations including chemotherapy can have severe (but often temporary) side effects like nausea, dry heaves, exhaustion, and shortness of breath.
As with melanoma itself, each patient's situation and response to treatments will be somewhat different.
14) What is thought to cause melanoma?
No one knows
exactly what causes melanoma, but several risk factors have been
identified. One is ultraviolet radiation in general, but especially
sunburn in childhood. Secondly, people with large or irregularly shaped
are more likely to get melanoma. It appears that a tendency toward
could be inherited.
Melanoma lesions do not necessarily manifest themselves in areas that have EVER had direct sun exposure. In other words, it is imperative to check parts of the body that have not been directly exposed to the sun-on the head under a full head of hair, behind the ears, genital areas, between the toes, etc.
15) What are monoclonal antibodies?
Monoclonal antibodies target a specific antigen. They may one day be useful in cancer diagnosis and treatment. At the present time, they are being studied in clinical trials. NovoPharm, a Canadian pharmaceutical company, said its Gliomab-H, a human monoclonal antibody, is an active agent against brain tumors, melanoma, and neuroblastoma. Unlike most forms of conventional cancer therapies that target only dividing cells, Gliomab-H targets cancer cells that are both resting and actively dividing.
16) What is a PET scan?
The PET scan (Positron Emmission Tomography) is a relatively new technology and there are few PET units in medical centers at the present time. The scan measures "metabolically active sites" in the body. PET has about 90%+ accuracy for detecting all types of tumors, but since melanoma is so active metabolically, PET has even better accuracy stats for detecting melanoma.
17) What is Essiac Tea?
Essiac Tea is an herbal combination reputed to cure cancer. It is also marketed under the name Flor-Essence. The tea is available through the natural products distribution channel, and your local health food store can order it for you. Ralph Moss PhD, gives a list of components of Essiac and other info at: http://www.iinet.net.au/~essiac/1essiac7.html
18) What are the recommended tests to follow up with after a melanoma diagnosis?
Commonly, doctors recommend complete checkups every 3 months for 2 years, then every 6 months for another 3 years. At these checkups, your doctor will probably do a complete skin examination and palpate all the major lymph node groups and the abdomen. Along with these examinations, many doctors order a lung x-ray every 6 months and a lung, brain, and abdominal CT scan every year. Other diagnostic tests may include the PET scan and blood tests.
19) What is the Gamma knife?
knife is 204 localized beams of radiation pointed directly at the
tumor. It does not penetrate the surrounding area. It is performed by
doctors-a neurosurgeon, a physicist (at the computer) and an
radiation is highest at the center of the tumor and breaks up the DNA
tumor can no longer replicate. The Gamma knife is a stereotactic
cobalt source machine.
20) What are the different types of machines for Stereotactic Radiosurgery?
*The linear accelerator provides very precise, uniform irradiation for stereotactic radiosurgery of brain tumors. Importantly, this device allows "fractionation" of treatment that allows the safe administration of a higher dose of radiation than can be given with the machines using multiple cobalt sources. Fractionation means that the treatment is divided into multiple smaller doses (fractions) of radiation. The reason for fractionation is to improve the radiation effect on the tumor while minimizing the effect on the normal brain. Normal brain tolerates small, daily doses of radiation relatively well. The tumor does not tolerate the small daily doses, resulting in control of the tumor. By exploiting this difference in response, the fractionated treatment can be very effective in reducing or even eliminating the tumor while sparing the normal brain.
The linear accelerator produces radiation having a higher energy than that produced by the cobalt-source machine. Further, the collimators or beam-shaping devices can be larger for the linear accelerators, resulting in much greater uniformity of dose for the larger
*The cobalt source machines are also very precise. However, because the frame has to be bolted on to the patient's head with metal bolts, fractionation of treatment is not possible. Further, the cobalt source machines have smaller collimators that may render larger tumors more difficult to treat with a homogeneous dose of radiation.
*The proton radiosurgery derives its advantage from the so-called "Bragg peak" that describes deposition of radiation dose from proton beams. As the
protons in the beam slow down in tissue, they give up (deposit) disproportionately more radiation per unit of travel. Just before the protons stop, they give up almost all their energy, resulting in a "peak" at that depth in tissue. The depth can be precisely defined by the energy imparted to the proton beam by
the cyclotron that produces the beam. Proton beam therapy is useful for many skull base tumors and vascular malformations of the brain.
*The Peacock system uses "inverse" treatment planning to make a very conformal distribution of the radiation dose in the tumor. It works in a way similar to a CT scanner to precisely determine the amount (weight) for each of manysmall beams that irradiate the target. This system also allows fractionation.
Ref: Johns Hopkins-Brain Tumor Treatments
site at: http://www.med.jhu.edu/radiosurgery/faq/
21) What is the difference between an undifferentiated cancer cell and a differentiated cancer cell?
An undifferentiated cancer cell is one that looks and acts very different from a normal cell, while a differentiated cell looks pretty close to a normal cell. There are degrees of differentiation in between. The more poorly the cancer cell is differentiated, the more aggressive it is.The MEL-L FAQ was developed by Gurudarshan Khalsa to get much-needed information and resources into the hands of melanoma patients and support people and is the official page of MEL-L. Excerpts from contributors' responses are attributed where possible. Pointers to WWW resources are suggested for further investigation. Hopefully, no copyrighted material has been wrongly reproduced. Upon awareness of any copyright matters we will remove it and seek the appropriate permission.
Selected Research Abstracts on Melanoma
Strategies and challenges in eliciting immunity to melanoma
Immunol Rev. 2008 Apr
Beirne Carter Center for Immunology Research, Department of Microbiology, University of Virginia School of Medicine, Charlottesville, VA, USA.
The ability of CD8+ T cells to recognize melanoma tumors has led to the development of immunotherapeutic approaches that use the antigens CD8+ T cells recognize. However, clinical response rates have been disappointing. Here we summarize our work to understand the mechanisms of self-tolerance that limit responses to currently utilized antigens and our approach to identify new antigens directly tied to malignancy. We also explore several aspects of the anti-tumor immune response induced by peptide-pulsed dendritic cells (DCs). DCs differentially augment the avidity of recall T cells specific for self-antigens and overcome a process of aberrant CD8+ T-cell differentiation that occurs in tumor-draining lymph nodes. DC migration is constrained by injection route, resulting in immune responses in localized lymphoid tissue, and differential control of tumors depending on their location in the body. We demonstrate that CD8+ T-cell differentiation in different lymphoid compartments alters the expression of homing receptor molecules and leads to the presence of systemic central memory cells. Our studies highlight several issues that must be addressed to improve the efficacy of tumor immunotherapy.
BRAF and NRAS mutations in melanoma: potential relationships to clinical response to HSP90 inhibitors.
Mol Cancer Ther. 2008 Mar 28
Signal Transduction and Molecular Pharmacology Team and Clinical Pharmacology Team, Cancer Research UK Centre for Cancer Therapeutics, The Institute of Cancer Research, The Royal Marsden Hospital, Sutton, United Kingdom; and Signal Transduction Team, Cancer Research UK Centre for Cell and Molecular Biology, The Institute of Cancer Research, London, United Kingdom.
Oncogenic BRAF and NRAS mutations are frequent in malignant melanoma. BRAF that is activated by the common V600E and other mutations, as well as by upstream NRAS mutations, has been shown to require the molecular chaperone heat shock protein 90 [HSP 17-allylamino-17-demethoxygeldanamycin (17-AAG)]. Here, we explore the possible relationship between tumor BRAF and NRAS mutations and clinical response to 17-AAG in six patients with metastatic malignant melanoma who received pharmacologically active doses of 17-AAG as part of a phase I clinical trial. One patient with disease stabilization for 49 months had a (G13D)NRAS mutation and (WT)BRAF. A second patient who had stable disease for 15 months had a (V600E)BRAF mutation and (WT)NRAS. These preliminary results suggest that BRAF and NRAS mutation status should be determined in prospective phase II studies of HSP90 inhibitors in melanoma. [Mol Cancer Ther 2008;7(4):737-9].
Cutaneous head and neck melanoma: the old and the new
Expert Rev Anticancer Ther. 2008 Mar
Roswell Park Cancer Institute, Department of Head & Neck Surgery & Plastic Surgery, Buffalo, NY-14263, USA. email@example.com
The incidence rate of malignant melanoma has shown a rapid worldwide rise in recent years. The staging and management of head and neck melanoma presents some unique challenges. Surgery remains the cornerstone of treatment, while sentinel node biopsy is the most accurate staging modality for regional disease. The complex regional anatomy and lymphovascular drainage of this region may account for the increased biologic aggressiveness and treatment challenges of this disease. Improved understanding of the radiobiology of melanoma has resulted in new adjuvant radiotherapy approaches, yielding improved control rates. The treatment outcomes of metastatic head and neck melanoma remain disappointing but important progress has been made in the understanding of melanoma biology.
Sentinel lymph node mapping in gynecologic malignancies.
Int J Gynaecol Obstet. 2007 Oct
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI 48109-0276, USA.
Lymph node status is the most important prognostic factor for women with vulvar, cervical and endometrial carcinoma and complete lymph node dissection has historically been an integral part of the surgical treatment of these diseases. Lymphadenectomy can be morbid for patients, who may experience wound breakdown, lymphocyst formation or chronic lymphedema, among other problems. Sentinel lymph node mapping is a newer technology that allows selective removal of the first node draining a tumor thereby allowing a potentially less aggressive procedure to be performed. Sentinel node mapping is well accepted for the management of breast carcinoma and cutaneous melanoma, and has resulted in reduced morbidity without adversely affecting survival. Sentinel node mapping is currently being investigated for treatment of gynecologic cancers. Recent studies show promise for incorporating the sentinel node mapping technique for treatment of several gynecologic malignancies.
Inguinal node dissection for melanoma in the era of sentinel lymph node biopsy
Surgery. 2007 Jun
With the introduction of sentinel lymph node (SLN) biopsy for melanoma, inguinal lymph node dissections (ILND) are more commonly performed for microscopic disease than for clinically palpable disease. We sought to examine the effect this change has on the morbidity of the operation.
A retrospective review was performed of all patients who underwent an ILND for melanoma between October 1997 and April, 2006. Clinical and pathologic data were collected and correlated by multivariate analysis with the incidence of a major wound complication.
We identified 212 patients, 132 who underwent an ILND for a positive SLN and 80 for clinically palpable disease. Age, sex, and body mass index (BMI) were similar in both groups. Patients with clinically palpable disease had a significantly greater number of involved nodes (3.0 vs 1.96, P = .0013), more often had ≥4 involved nodes (29% vs 9%, P < .001), and a greater incidence of extranodal extension (47% vs 5%, P < .001). Of the 212 patients, 41 (19%) had a significant wound complication. This complication was significantly higher among patients with clinical disease compared to patients with a positive SLN (28% vs 14%, P = .02). Only BMI (odds ratio of 1.1) and the indication for the procedure (odds ratio of 2.2) were independent predictors of a major wound complication. Lymphedema occurred in 30% of the patients and was only significantly associated with clinical disease (41% vs 24%, P = .025). With a median follow-up of 2 years, regional recurrence was not significantly greater in patients with clinically palpable disease (13% vs 9%, P = not significant [ns]), although this result was possibly due to the significantly greater rate of distant recurrence (49% vs 18%, P < .001) and death (48% vs 21%) in these patients.
Patients undergoing an ILND for a positive SLN have a significantly lower risk of postoperative complication or lymphedema than do patients undergoing ILND for clinically palpable disease. There is a benefit in regard to the morbidity of treatment in surgically staging melanoma patients by SLN biopsy and preventing ILND for palpable disease.
Complications after sentinel lymph node excision in patients with malignant melanoma
Ann Dermatol Venereol. 2007 May
Clinique Dermatologique, Hôpital Charles Nicolle, Rouen Cedex, France.
INTRODUCTION: Side-effects occurring after sentinel lymph node excision in malignant melanoma patients have been poorly evaluated to date. The aim of the present study was to assess the side-effects of sentinel lymph node excision in this population.
PATIENTS AND METHODS: All consecutive malignant melanoma patients undergoing sentinel lymph node excision between March 2000 and December 2002 were included in this retrospective study. Patients with a metastatic sentinel node subsequently undergoing lymph node dissection were excluded. Median follow-up of patients was 12.6 +/- 8.8 months. Complications were classified as "early" (i.e. occurring the month following surgery), or "late" (after this time).
RESULTS: Forty malignant melanoma patients (17 males, 23 females) with a normal histologic examination of their sentinel lymph node were included. They belonged to a series of sixty-one melanoma patients undergoing lymph node excision. Fourteen complications were observed in ten patients. Two early complications were seen: hematoma (n=1) and deep venous thrombosis with pulmonary embolism (n=1). Twelve late complications were observed: mild lymphoedema (n=5), hypertrophic scars (n=2), painful scars (n=4), and one chronic seroma (n=1). Many complications (33%) were observed after excision in the inguinal area.
DISCUSSION: The complications of sentinel lymph node excision must be considered in determining the benefit/risk ratio of this technique.
Externa; Abstracts and Studies:
Melanoma Resources:- - - - - -
Melanoma - Medlines Plus Information and Links Page
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Melanoma - National Cancer Institute
The Skin Cancer Foundation
PubMed - NIH Research Abstracts
Cancer Resources and Information:
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Your Body After Cancer Treatment
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Cancer Information on the Internet
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Cancer Resource Center
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Cancer Information & Support International
ICD-0 M8720/3 - http://www.progenetix.org/cgi-bin/pgHome.cgi
OMIM 155600 - http://omim.org/entry/155600
Disease DB 7947 - http://www.diseasesdatabase.com/ddb7947.htm
MedlinePlus 000850 - http://www.nlm.nih.gov/medlineplus/ency/article/000850.htm
Plastic/456 - http://emedicine.medscape.com/article/1295718-overview#
MeSH D008545 - http://www.nlm.nih.gov/cgi/mesh/2011/MB_cgi?field=uid&term=
WHAT IS IT?
Lymphedema is a buildup of a fluid called lymph and protein in the tissues under the skin. Lymph accumulates when there is an obstruction to normal flow causing swelling, usually in an arm or leg. The lymph system is similar to the blood system in its network of vessels that carry lymph fluid throughout the body.
Trauma to lymphatic tissue by surgery or radiotherapy is the main cause of lymphedema in the context of cancer. It can result from surgery and/or radiation therapy during treatment for cancers of the breast, abdomen, melanoma, connective tissues (sarcomas) and the pelvic area, as well as lymphomas, in both men and women. Lymphedema may also be the result of infection, such as dermatophytosis in the foot.
Cancer tumors also can block the lymph vessels, especially in people with prostate cancer or lymphoma.
IF I HAVE CANCER WILL I DEVELOP LYMPHEDEMA?
Not necessarily. The most frequent cases occur in women with breast cancer; 10% to 25% of breast cancer patients will develop lymphedema. While most cases are mild, approximately 400,000 women cope daily with some degree of disfigurement, discomfort, and sometimes disability because of arm and hand swelling.
Because of improvements in radiation and surgical techniques (such as removing smaller samples of lymph nodes), lymphedema is less common today than it use to be. Lymphedema develops in about one in four breast cancer patients who have a mastectomy with lymph-node dissection. The risk doubles for those who also receive radiation treatments to the underarm area.
Radical prostatectomy, a procedure that removes the prostate gland, seminal vesicles and sometimes the nearby pelvic lymph nodes, can lead to lymphedema .One type of Kaposi’s sarcoma is called the lymphadenopathic form that can spread throughout the body and may aggressively involve lymph nodes, viscera, and occasionally the GI tract – resulting in a kind of lymphedema.
SENTINEL LYMPH NODE BIOPSY
If breast cancer spreads, it first goes to the lymph nodes under the arm. That's why women with breast cancer have these nodes examined. Until recently, surgeons would remove as many lymph nodes as possible, but this greatly increased the risk of lymphedema. More recently, a growing number of physicians have begun focusing on finding the sentinel nodes — the first nodes to receive the drainage from breast tumors and therefore the first to show evidence of cancer’s spread. Experts believe that if a sentinel node is removed and found to be healthy, then the chance of finding cancer in any of the remaining nodes is very small and no other nodes need to be removed. This spares as many as 75% of women who have no evidence of tumor spread to the axillary nodes the risk of complications, especially lymphedema.
WHEN DOES IT DEVELOP?
Lymphedema can appear any time after surgery or radiation treatment including many years later.
When the condition develops very soon after surgery, it is usually mild, and goes away within one to two weeks. It can also develop six to eight weeks after surgery or radiation. Again, this type of lymphedema usually goes away in a few weeks.
Unfortunately, the more common form of lymphedema in cancer survivors develops slowly over time. It may show up many months or even years after treatment ends and swelling can range from mild to severe. In most cases however, lymphedema appears between six and 12 months after treatment. While people who have many lymph nodes removed and radiation therapy have the highest risk of developing lymphedema, some high-risk patients won’t develop the condition.
WHEN TO CALL A PROFESSIONAL
Patients should contact a physician if they had a mastectomy, lower abdominal surgery or radiation treatments in the past, and the affected limb becomes red, painful or hot, or if it develops open sores or areas of broken skin. Doctors should be consulted especially if there is a fever in addition to swelling.
Usually, no specific testing is necessary to diagnose lymphedema, but tests may be done such as a blood count that can identify signs of infection. Ultrasound may be ordered to look for blood clots, which can cause swelling. Computed tomography (CT) may be used to find a tumor that could be blocking lymph vessels. In addition, there are more specialized tests that can identify lymph flow and lymph vessel abnormalities.
The first signs of lymphedema can be a change in a patient’s arms or legs or other affected area such as the groin. Initially, skin will remain soft, but if the problem continues, the limb may become hot and red and the skin hard and stiff. The lymph fluid that collects in the tissues can be very uncomfortable, but pain is not always present. Early symptoms of lymphedema may include:
In most cases, only one arm or leg is affected. If the leg is involved, swelling usually begins at the foot, then progresses upward toward the ankle, calf and knee.
The severity is directly related to the extent of surgery and radiation treatment to the lymph nodes. Severity and general risk of developing lymphedema seems to increase with obesity, weight gain and infection in the affected area.
Lymphedema has no cure so treatment focuses on reducing the symptoms. Treatment has varied from virtually no treatment to surgery, but there are various practical methods to deal with the condition, including elevation of the limb (in the first year only), compression garments (no greater than 20-30 mm Hg), certain types of massage and exercises, pneumatic compression devices (controversial), and other types of physical therapy. Experts also recommend keeping the affected limb clean, dry and lubricated.
The National Lymphedema Network (www. Lymphnet.org) encourages massage by an specially certified expert in lymphedema massage.. In many cases, patients can also be trained to massage themselves to improve the flow of lymph fluids.
There are no medications to treat lymphedema. Diuretics have been found to be ineffective and may actually exacerbate the condition. Other medicines have been tried, but there is no clear evidence of significant effectiveness with any particular drug.
arm or leg above the level of the
heart(during the first year) and flexing it frequently are basic
manage the condition. Since elevation is impractical except for short
patients should be fitted with an elastic sleeve, covering the arm or
A significant reduction in edema (swelling) has been reported after wearing elastic sleeves for 6 consecutive hours per day. Using these garments during exercise, physical activity, and especially air travel is recommended, since air travel seems to exacerbate the condition.
If the legs are affected, avoid periods of prolonged standing. If working or standing a lot, a doctor may prescribe special graduated compression stockings to wear throughout the day. A doctor may also suggest a protein-rich, low-salt diet for those who are over-weight or obese.
MODERATE TO SEVERE:
For people with moderate to severe lymphedema in the legs, doctors prescribe pneumatic compression devices to be used at home to help reduce limb swelling. The “pneumatic stockings” are worn every day for an hour or two to reduce the swelling. Once the swelling has been reduced, a person may still need to wear elastic stockings up to the knee every day from the moment of rising until bedtime.
For lymphedema in the arm, pneumatic sleeves--like pneumatic stockings--can be used every day to reduce the swelling; elastic sleeves may also be needed.
Others recommend a special type of massage therapy called manual lymph drainage. Antibiotics also may be prescribed to prevent or treat infection in the affected limb. Since skin infections can be more serious in people with lymphedema, a person may need to have antibiotics administered intravenously in the hospital during an infection.
Complex Decongestive Therapy
More serious cases of lymphedema can be treated with Complex Decongestive Therapy by a physical therapist or other health care professional, who has special training. Complex Decongestive Therapy consists of skin care, massage, special bandaging, exercise, and fitting for a compression sleeve. Seeking and getting treatment early should lead to a shorter course of treatment to get the lymphedema under control. While most insurance companies will pay for this treatment, some do not.
certified in the procedure should perform
Manual Lymph Drainage (MLD).
In the case of lymphedema of the arm, the procedure involves a type of massage that moves built up fluid around the blocked vessels and across the chest to the other side of the body where the lymphatic system is still in tact. Usually the healthy area will be “worked” first. After each treatment, the effected area is carefully bandaged with a special layered wrap that looks like an ace bandage but is made of a different fabric. The wrap is important for keeping the effected limb de-congested. An average course is 15 daily treatments of 60 to 90 minutes each. After a MLD course of treatments, the patients will wear a compression garment every day. The patient should be measured for a new compression sleeve every six months or so. Sometimes a yearly MLD treatment course is recommended as a kind of “tune up.”
lymphedema development may occur even
after several decades, patients should monitor themselves for signs of
lymphedema and report any changes to their physicians.
Prevention is important and can require daily attention to manage the symptoms of swelling in particular. Arm and hand precautions are based on two key ideas: (1) Do not increase lymph production, which is directly proportional to blood flow, and (2) do not increase blockage to lymph system. Therefore, patients should avoid excessive heat, infections, and overly-strenuous arm exercises which would increase blood flow in the arm and thereby increase lymph production.
Patients should follow these suggestions to manage their lymphedema:
It is important to use your affected limb for normal everyday activities, yet overuse can cause lymphedema to occur in some people. Follow these suggestions whenever possible:
For More Information
American Cancer Society
The American Cancer Society held an international conference on lymphedema in 1998 in New York City. It involved 60 of the world’s leading experts and included a forum of more than 250 breast cancer survivors, leaders of breast cancer advocacy groups, and others. The conference report plus a lymphedema resource guide are available as a book from the ACS at cancer.org. (See below for title.)
National Lymphedema Network
Lymphedema Network is a charitable
organization with an international scope. Founded in 1988, the
mission is to provide education and guidance to patients and health
professionals. The Network promotes standardizing quality treatment for
lymphedema patients. In addition, the organization supports research
causes and possible alternative treatments for this “often
Lymphedema is swelling,
People Cancer Information Pages
Cervical, ovarian Cancer
Kidney and Renal Cancer
Hodgkins Disease or Hodgkins Lymphoma
Leg Lymphedema After Gynecological Cancer
Primary Lymphedema and Cancer
Cutaneous T-cell Lymphoma
Cutaneous B-cell Lymphoma
My Life with Lymphedema and Lymphoma
Lymphedema Affects Quality of Life
Angiosarcoma and Long Term Lymphedema
Male Breast Cancer
Lymphedema After Cancer - How Serious Is It?
Secondary Lymphedema in the Cancer Patient
Complications of Breast Cancer Radiotherapy
Complete decongestive therapy lymphedema in breast cancer
Patient self-massage for breast cancer-related lymphedema
Predictive Factors of Response to Intensive Decongestive Physiotherapy in Upper Limb Lymphedema After Breast Cancer Treatment: a Cohort Study
Lymphedema Therapy and the Quality of Life for Breast Cancer Patients
Cancer Associated with Lymphedema
Pseudolymphomatous Cutaneous Angiosarcoma: A Rare Variant of Cutaneous Angiosarcoma Readily Mistaken for Cutaneous Lymphoma.
Papillomatosis cutis carcinoides
Related Terms: Verrucous Carcinoma, Squamous Cell Carcinoma, Epithelioma cuniculatum, Carcinoma cuniculatum
Cutaneous lymphomas assoc with lymphoproliferative disorders
Aqua Lymphatic Therapy for Postsurgical Breast Cancer Lymphedema
Sporadic Cutaneous Angiosarcomas
Axillary node biopsy
Sentinel Node Biopsy
Small Needle Biopsy - Fine Needle Aspiration
Extraperitoneal para-aortic lymph node dissection (EPLND)
also includes (1) Retroperitoneal Lymph Node Dissection and (2) Laparoscopic Retroperitoneal Lymph Node Dissection
Magnetic Resonance Imaging
Lymphedema People Online Support Groups
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Support group for parents, patients, children who suffer from all forms of lymphangiectasia. This condition is caused by dilation of the lymphatics. It can affect the intestinal tract, lungs and other critical body areas.
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Page Updated Apr 19, 2012