Hope for first drug against lymphedema

Many cancer patients, especially those who've undergone breast cancer treatment, experience painful, swollen limbs, a condition called lymphedema. Now researchers say they've found an underlying mechanism that could eventually lead to the first drug therapy for the debilitating condition. The findings come from research in mice and human cells. However, there's already a clinical trial underway to see whether these lab discoveries will translate into a new lymphedema treatment. It's estimated that 10 million Americans have lymphedema, said Dr. Stanley Rockson, one of the senior researchers on the study.

"Even though many people might not recognize the term, it's a very common condition," said Rockson, a professor at Stanford University School of Medicine in Stanford, Calif. People with lymphedema have excess fluid buildup in parts of the body, usually the arms or legs. Most often, the condition arises after certain cancer treatments damage the lymphatic system, preventing lymph fluids from draining properly. Right now, there is no cure or drug therapy for lymphedema, Rockson said. Instead, it's typically managed with measures such as massage, compression garments and pneumatic compression devices. Lymphedema is not just a cosmetic issue: It can be uncomfortable, hinder range of motion, and make people vulnerable to infections, according to the American Cancer Society. "It can severely limit physical and social functioning," Rockson said. In the new study, he and his colleagues aimed to get a clearer understanding of the molecular mechanisms that drive lymphedema. So they turned to a drug called ketoprofen.

The drug, a painkiller, has actually been studied as a lymphedema treatment. The problem, according to Rockson, is that ketoprofen can have side effects for the heart, gastrointestinal tract and kidneys. Safer alternatives are needed, he said. To zero in on ketoprofen's good side — its action against lymphedema — the researchers used lab mice induced to have a lymphedema-like condition. The scientists found that the drug prevented tissue injury and fluid buildup by blocking a protein called leukotriene B4 (LTB4). It turned out that the same protein was elevated in cell samples from lymphedema patients. And not only ketoprofen battled lymphedema in mice. Another drug called bestatin worked just as well. Bestatin is not approved in the United States, but it has been used for years in Japan as a cancer treatment. The advantage of the drug, according to Rockson, is that it has more "selective" action against LTB4 — and fewer side effects — than ketoprofen. Based on the lab findings, a clinical trial testing bestatin against lymphedema is already underway, Rockson said. Eiger BioPharmaceuticals, based in Palo Alto, Calif., is funding that trial (and acquiring the drug from its Japanese manufacturer). Rockson and a colleague on the study are consultants to the company. "I think patients should feel very encouraged that work is being done," said Dr. Theresa Gillis, chief of the rehabilitation service at Memorial Sloan Kettering Cancer Center in New York City.

Still, the role of bestatin — if any — won't be clear until the clinical trial results are in, according to Gillis, who wasn't involved in the research. The "mouse model" of lymphedema, she noted, doesn't exactly replicate what happens in cancer patients who undergo radiation therapy or surgical removal of the lymph nodes. And, treatments that work well in animals don't always pan out in people. Gillis agreed that new lymphedema treatments are badly needed. "Millions of dollars are spent each year in the U.S. on treatment of lymphedema," she said. "And those millions are often costs carried by the patients themselves." Beyond costs, Gillis added, the current therapies are burdensome. "Patients with severe lymphedema wear specialty compression garments daily, and may need to use compression bandaging every night — or a second specialty night garment," she said. "Even with optimal efforts by the patient, edema can become progressively worse over time."

The new findings offer a clearer understanding of the underlying process in lymphedema, according to Gillis. Hopefully, the new understanding will "lead us toward eventually preventing the condition altogether," she said. The bestatin trial results are a few years away. But Rockson said he thinks patients can take heart in the fact that the work is happening. "Historically," he said, "lymphedema patients have been largely ignored, and that's led to a certain sense of hopelessness. But now I think we can say answers are on the horizon."

Breast Cancer Survivors May Knock Out Lymphedema by Weightlifting

Though stigmatized for a long time, more women are finally starting to come into the world of weightlifting, which offers numerous health benefits – especially for survivors of breast cancer. A recent study published in the journal Supportive Care in Cancer found that it may prevent, or even reverse, lymphedema, a common side effect in patients with breast cancer.

Researchers at Florida State University looked at 27 women who finished primary breast cancer treatment. These women took part in a supervised exercise program that consisted of resistance training twice a week for six months to see what kind of effect this type of exercise would have on lymphedema. “There were only a couple of ladies who had some swelling in their arms,” Lynn B. Panton, Ph.D., FACSM Professor Department of Nutrition, Food & Exercise Sciences at FSU and author on the study, said in an interview with CURE.

“In some ladies, it showed that there was a decrease in the swelling.” The full-body regimen included various machine-based exercises of two sets of eight to 12 repetitions. When a participant used the same weight for 12 repetitions two sessions in a row, she would move on to a heavier weight. Arm circumference was measured at baseline and then every two weeks throughout the study. At the start of the study, three women had pre-existing lymphedema and two of them wore a prescribed compression sleeve to every workout session. No signs of exacerbation were found in all three of the women, and no participant experienced any lymphedema-related adverse events. Panton noted that some of the women were apprehensive about starting an exercise that included weight training.

Not only is there a stigma around women lifting weights – especially for older patients – but doctors also caution patients not to do any upper body exercise for six to eight weeks after surgery. “But then nobody really said, ‘OK, now you’re free to do whatever exercise,’ and a lot of the time, these ladies are scared to do something with their upper body,” Panton said. “And still, there is a stigma for a lot of women with strength training. I wish they would all do it because it’s so beneficial.”

Besides its role in mitigating lymphedema complications, resistance training also proved to help with osteoporosis, a common side effect seen with cancer treatments, and the onset of menopause, as well as overall functionality and quality of life. “It’s huge. The women said that they could do things that, even before surgery, they hadn’t been able to do,” Panton said, citing examples such as carrying groceries and picking up grandkids. “It’s an empowerment and it gives them that self-esteem. The body image improves, too, which is so important.”

Most of the exercises that the women did on the study can also be done with free weights, such as barbells and dumbbells, though patients should be especially cautious if they choose this route—making sure they have the proper technique and balance to safely perform each movement. And, as with any exercise regimen, it is important that patients and survivors speak with their medical team and get their doctor’s clearance before starting resistance training. Even if this type of exercise is not right for some patients, getting out there and moving – in whatever way possible – is key, Panton said. She and her team look to study the results of body weight and impact exercise in the future. 

“Any exercise is important,” she said. “Even for patients who are currently dealing with treatment—if they could at least get out there and do some physical activity, I know it’s difficult, but they do so much better in the long run.”

New breast cancer procedure helps prevent lymphedema

By Petrina J. Johnson

Axillary reverse mapping, a breast cancer procedure involving the removal of cancerous lymph nodes, is helping prevent lymphedema in patients.

Dr. Leonidas Miranda of North Houston Specialty Physicians, said the procedure is relatively new but very important. ARM was developed by Dr. V. Suzanne Klimberg, a breast surgeon. Miranda, a general surgeon, said he begin using the procedure about a year ago. Miranda said ARM is a major improvement because it decreased the risk of lymphedema down to 4 to 7 percent.

“In the old days we use to take the lymph nodes from the arms and breasts,” said Miranda. “This is why there was such a high rate of lymphedema, 20 to 25 percent.”

The previous procedure was a great experience but the high risk for patients developing lymphedema made it what Miranda described as a “sad situation.” It was something he said the patients should not have to endure.

“On top of the fact that they (the patients) had to go through all these treatments they had developed swollen of the arm,” said Miranda.

The new procedure, Miranda explained, helps to identify the lymph nodes coming from the arm. He said ARM involves injection of a special blue dye under the skin in the arm. The blue dye travels through the lymphatic (channels) in the arm. Miranda said the lymph nodes that are blue help the surgeons know which ones are coming from the arm.

“When you open the arm pit you see them (lymph nodes) and then you don’t take them, this is what axillary reverse mapping is,” said Miranda. “When you see those lymph nodes you only take the ones that are not blue.”

Miranda said because the surgeons do not have to remove the lymph nodes from the arm, it helps preserve the return circulation coming from the arm. This helps to prevent lymphedema.

“It does add a few more minutes to the procedure (the operating time) but it is well worth it,” said Miranda.

How to Prevent and Manage Lymphedema

From the Dana-Farber Cancer Institute

Following radiation treatment or surgery to remove lymph nodes (lymphadenectomy), patients can develop lymphedema, a condition that involves abnormal swelling, usually in the arms or the legs, due to an accumulation of lymphatic fluids. This fluid buildup is caused by blockage or removal of lymph nodes or lymph vessels.

Lymphedema is often associated with breast cancer patients, but can result from treatment of other cancers, such as melanoma, prostate, or advanced gynecological cancer.

In addition to discomfort, lymphedema can also lead to infection, as the fluid buildup can increase bacteria growth. Pay attention to signs of infection, including pain, heat, swelling, rash blistering, redness, and fever. If you notice these symptoms, call your physician immediately.

Below are some ways to prevent infection and manage lymphedema symptoms that arise:

Infection prevention techniques:

*Be sure to keep your skin clean and moisturize daily.
*Exercise when possible. A physical therapist can help you determine what types of exercise your body can handle. 
*Avoid injury (cuts, sunburns, and insect bites) and wear gloves for gardening or cleaning.
*Avoid injections and blood pressure readings in the surgery site, or in the area that is affected by lymphedema.

Lymphedema management tips:

*Do not lift heavy objects with an arm affected by lymphedema and avoid continuous circular motions, like mixing.
*Elevate the limb above heart level as often as possible.
*Avoid extreme temperature changes when bathing or alternating between ice packs and heating pads.
*Avoid constriction. Wear loose clothing, do not wear tight jewelry or elastic bands around affected fingers or arms.
*Maintain ideal weight and a diet rich in protein and low in salt. 
Read more about how patients can keep a healthy diet.

If lymphedema is caused by infection, a doctor can prescribe antibiotics. If not, mechanical compression sleeves and stockings can prevent further accumulation of fluid in the affected limb. A trained therapist can also introduce manual lymphatic draining, if necessary.
 

Certain surgeries may lead to limbs swelling

Stephanie Turner, Aiken Standard

For some people, they will never be fully healed. An illness has crept inside them, swelling their limbs to abnormal sizes.

This swelling can be a sign of lymphedema, according to Holly Shurtleff, Hitchcock Healthcare occupational therapist.  "You can eat perfectly healthy and be the ideal weight, and, yet, you can still get lymphedema," she said.

March is deemed Lymphedema Awareness Month.

"This illness can be really scary," Shurtleff said.
Lymphedema stems from your body's lymphatic system, which helps protect our bodies from germs and bacteria, as well as help us release waste, Shurtleff said.

"It is part of the circulatory system of veins and arteries," says the National Lymphedema Network.

Shurleff explained that the "controlling center" of the lymphatic system are called the lymph nodes, which are located in the lymph vessels.

When lymph fluid passes through these nodes, they rid the fluid of harmful bacteria and viruses.

"Networks of the lymphatic system comprising these vessels ... and nodes are situated in several areas of the body," the National Lymphedema Network stated.

These networks reach places like the neck, the armpits, the pelvic area and the groin.

Surgery that results in the lymph nodes being removed are one way a person can get lymphedema. These surgeries are often used as treatment methods for cancer patients, Shurtleff said.

"Surgical removal of a tumor and adjacent lymph nodes and vessels may block lymph fluid from flowing naturally through its system," the National Lymphedema Network says.

Having radiation therapy can also leave its effects by causing scar tissue to form. This will also disturb the flow of lymph fluid.

Some are born with lymphedema, Shurtleff said.  "The whole baby's body can swell," she said.

If the swelling goes untreated, your skin can harden and/or you can get infections, the National Lymphedema Network stated.

Treatment methods include exercising, using compression garments and bandages and taking antibiotics. Methods are determined based on the cause and severity of the illness, the National Lymphedema Network stated.

Your affected limb can return to its normal size but only if it swelled up to less than 5 percent of its normal size, Shurtleff said.

"The further it is, the greater the possibility it won't get back to your normal size," she said.

One treatment method she uses is massaging. That and exercise can "get the fluid moving throughout the whole area," she said.  Lymphedema cannot be cured, she added.

The swelling can reoccur; therefore, those with this ailment must take precautions.

Besides keeping your weight to a healthy level, avoid wearing tight jewelry and doing stressful movements with the affected limb. Avoid injuries by wearing protection as you work around the house or at your job. Keep the limb away from heat, and keep it elevated as much as possible.

Those with affected limbs should not to get blood drawn or shots put into them.

Those who need to have their lymph nodes removed can work to prevent themselves from catching lymphedema, Shurtleff said.

After surgery, be sure to drink plenty of fluids, protect the limb and exercise.

If you are experiencing unusual swelling and discomfort, tell an oncologist or your regular physician.

For more information on lymphedema, visit www.lymphnet.org.

Innovations Target Risk of Lymphedema After Cancer Treatment

By NARA SCHOENBERG | CHICAGO TRIBUNE 

In the past few years, surgeons have made strides in preventing lymphedema, a potential side effect of breast cancer surgery in which a blockage in the lymphatic system causes fluid buildup and swelling in the arm.

By preserving the underarm lymph nodes in patients with less-advanced cancer, surgeons have reduced the lymphedema risk for those patients.

But lymphedema still affects an estimated 10 to 40 percent of patients, depending on the extent of the cancer and the type of surgery and radiation required.

What can be done for patients whose underarm lymph nodes can't be preserved because of the spread of cancer? Or the ones who get lymphedema despite lymph node-saving surgery?

Approaches that may help are being tested and tried at major cancer treatment centers, among them the lymphatic microsurgical preventive healing approach (LYMPHA) surgical technique, which connects lymph vessels to a nearby vein, restoring drainage when underarm lymph nodes are removed. There's also axillary reverse mapping, which seeks to identify and preserve lymph nodes related to arm drainage (as opposed to breast drainage), and highly sensitive L-Dex bioimpedance spectroscopy, which is used to diagnose lymphedema at its earliest stages, when it is most responsive to treatment.

"There are a lot of people working on different things," said Dr. Sarah McLaughlin, a breast surgeon at the Mayo Clinic in Jacksonville, Fla.

But as much as researchers would like to see advances in this area, she said, it's important to wait until new approaches are backed up by reliable data.

"It just takes time," she said.

At NewYork-Presbyterian Hospital/Columbia University Medical Center, surgeons are seeking to replicate the results of a promising Italian study, in which researchers at the University of Genoa attempted to prevent blocked drainage after lymph node removal by allowing lymph vessels to drain into a nearby vein. In the Italian study, published in 2011 in the Annals of Surgical Oncology, 4 percent of the women in the LYMPHA group had lymphedema at six months after surgery, compared to 30 percent of the women in the control group.

The NewYork-Presbyterian pilot study started in January.

"We've performed this on about seven patients, and so far, it looks very, very good," said Dr. Sheldon Feldman, chief of breast surgery at NewYork-Presbyterian. The procedure takes less than an hour, and the technique is quite simple, he said: Lymphatic vessels are basically attached into a stump of a branch of a nearby vein.

Axillary reverse mapping, in which an injection of dye is used to identify the lymph nodes that drain the arm, as opposed to the breast, for the purpose of preserving the arm lymph nodes during surgery, is being used at some large cancer centers.

Early detection of lymphedema is the aim of L-Dex bioimpedance spectroscopy technology, which uses a small electronic current to detect volume change.

"The longer lymphedema is there, the tougher it is to treat, so the idea is to have a very sensitive tool which could be used to detect very subtle changes in volume in the arm - before it's apparent to the patient, before it's apparent to the doctor," Feldman said.

"That's what this bioimpedance spectroscopy can do."