My Life with Lymphoma and Lymphedema - Part Three

April 30, 2006

Since my last updated in December much has happened in my ongoing struggle with lymphoma and lymphedema.

I have continued the Rituxan treatments, and hopefully that is helping blunt and/or remove the lymphoma. This will be continued every three weeks for the next two years.

There has however, been a dramatic change in the lymphedema. For the last couple months, I have experienced significant over-all body lymphedema.

This includes incredible difficulty in breathing, significant new swelling now in both arms, abdomen, chest and even back.

For many years, I tried to get my former oncologist to understand that B-cell lymphoma with hereditary lymphedema would not follow the same progression path and lymphoma by itself.

As all this new lymphedema has occured, I have wondered how much of it is lymphoma...how much is just the lymphedema.

I ran accross quite by accident today, the first clinical report I have been able to locate on B-cell lymphoma and its overall effect on the lymph system itself. For me it is stunning, as it is verifiable proof of what I have been saying for years.

* * * * *

Density of intranodal lymphatics and VEGF-C expression in B-cell lymphoma and reactive lymph nodes.

Wroel T, Mazur G, Dziegiel P, Jelen M, Szuba A, Kuliczkowski K, Zabel M.

Department of Haematology, Blood Neoplasms and Bone Marrow Transplantation, Medical University, Wroclaw, Poland.

wrobelt@hemat.am.wroc.pl

Lymphatic vasculature in solid tumors may serve as the pathway for metastatic spread of the cancer to the regional lymph nodes and to distant organs. Controversy still exists whether tumors metastasize through existing lymphatics or through newly formed vessels (lymphangiogenesis). The role of lymphangiogenesis in lymphoma spread and proliferation is not clearly established.

VEGF-C is the most potent inducer of lymphangiogenesis. LYVE-1 was shown to be a specific marker for lymphatic vessels in normal and tumor tissue. The aim of the present study was the evaluation of lymph node LYVE-1-positive lymphatic sinus density (LSD) and VEGF-C expression in patients with non-Hodgkin's lymphoma (nHL) and in reactive lymph nodes. Sixty paraffin-embedded lymph nodes from newly diagnosed patients with B-cell nHL were evaluated. Twelve lymph node biopsy specimens from adult patients with reactive lymphonodulitis were used as controls. Sections of lymph nodes were stained immunohistochemically for LYVE-1 and VEGF-C.

VEGF-C expression in lymph nodes of nHL patients was low and not significantly different from that in the control (p = 0.6). Moreover, VEGF-C expression did not differ significantly between aggressive and indolent lymphomas (p = 0.53). Similarly we did not find differences in LSD in aggressive nHL and in indolent nHL (p=0.49). The mean LSD in reactive lymph nodes was higher than in nHL (p = 0.03). Only in 2 out of 12 reactive lymph nodes LYVE-1-positive vessels were absent.

In all groups we demonstrated a strong positive correlation between VEGF-C and LYVE-1-expression (p = 0.0001). Higher LSD in reactive lymph nodes as compared to those of nHL patients suggests that lymphoma proliferation leads to the destruction of the existing lymphatics rather than to lymphangiogenesis within lymph nodes. NHL are not associated with increased expression of VEGF-C nor increased LYVE-1-positive lymphatic sinuses density within lymph nodes.

PMID: 16584091 [PubMed - indexed for MEDLINE

Related Pages:

My Life with Lymphoma and Lymphedema Part One

My Life with Lymphoma and Lymphedema Part Two

Lymphedema and Lymphoma - an Update

Prognosis, with evaluation of general biochemistry, of liver disease in lymphoedema cholestasis syndrome 1 (LCS1/Aagenaes syndrome).

Drivdal M, Trydal T, Hagve TA, Bergstad I, Aagenaes O.

Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway. monica.drivdal@uus.no

OBJECTIVE:

To investigate the prognosis of liver disease in Aagenaes syndrome (lymphoedema cholestasis syndrome 1 (LCS1)), which is an autosomal recessive inherited syndrome consisting of neonatal cholestasis with intermittent cholestatic episodes in childhood into adulthood and development of lymphoedema. Forty Norwegian patients are known to have this condition, 25 of whom are alive. A clinical description of the liver disease is supplied with a case-control study.

MATERIAL AND METHODS:

In this paper we review the course of the liver disease in the Norwegian cohort of patients and present results from a case-control study in the patients above 10 years of age. The case-control study was performed on 15 patients without clinical cholestasis (itching and sometimes jaundice) at the time of the study. An evaluation of 11 patients above 15 years of age without chronic biochemical cholestasis (increased alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT) and/or serum bile acids) was also carried out. For each patient one randomly identified control person was included (15 in one study, 11 in the other).

RESULTS:

Cirrhosis with either transplantation or death in infancy or early childhood occurred in six patients; slowly developing cirrhosis occurred in three patients. Two patients may be in the process of developing cirrhosis. Significantly increased ALP and GGT levels were found in patients with normal liver biochemistry in the preceding years when compared with the case control group. Additionally, albumin was found to be lower in older patients.

CONCLUSIONS:

Compared with that for other types of hereditary neonatal cholestasis, patients with LCS1 have a relatively good prognosis. More than 50% can expect a normal life span.

PMID: 16635916 [PubMed - in process]

Related Article:

LYMPHEDEMA CHOLESTASIS SYNDROME

LYMPHEDEMA SHARP AAGENAES SYNDROME

Come Meet Steve Norton - Norton School of Lymphatic Therapy

**Special reminder for those in the North Georgia area**

May 4, 2006 - 7:00-9:00 pm (Thursday) --

LLN Support Group meets in Room J-8 at the Cecil B. Day Sports &Fitness Center in Dunwoody (1445 Mt. Vernon Drive, Atlanta, GA).

Program: Successful Treatment Techniques for People with Lymphedema, presented by Steve Norton with the Norton School of Lymphatic Therapy.Light refreshments will be served.Mark your calenders!!!!!!!! See you there or be square

Visit the Lighthouse Lymphedema Network

Also

Remeber you can check for auto updates on the

Lighthouse's Calender of Events

Pat

Exercise, Lymphedema, and the Limb at Risk

Exercise, Lymphedema, and the Limb at Risk
Bonnie B. Lasinski, MA, PT, CLT-LANA
How many clinicians are at a loss for words when they are asked about what kind of exercise is "good" for individuals with lymphedema? How many individuals living with lymphedema or a limb at risk for lymphedema have asked their healthcare professional for advice concerning exercise only to receive conflicting information? It is difficult to "recruit" presenters to provide workshops/discussions on exercise for both patients and professionals alike. Exercise and lymphedema - it is a controversial subject.

Twenty-four years ago, I was asked to do a presentation on exercise after mastectomy for a one day seminar sponsored by the American Cancer Society's Long Island Division, entitled "Living With Cancer". When I contacted the coordinator of the workshop, Diana Rulon, she informed me that she was not "interested in exercise after mastectomy - she was interested in exercise for lymphedema!"You can imagine my shock and fear at that moment. I had no special training in lymphedema management, in fact, no one did. We were just beginning to hear strange tales of a treatment from Europe that seemed ridiculously mild for the severe swellings I had seen in my limited experience. But, I figured no problem. I'll just go to the medical library, research the articles, and develop my talk from there.

Well, that was 1980 and there were no articles, except for a few abstracts of German and French studies. Now, I was really in trouble. Well, long story short, I was inspired by the dedication of Diana Rulon who tried to find help for other women like herself, who had long been ignored by their doctors and told to live with their problem. Thus began my journey in lymphedema management. Trial by fire, you might say! We presented a very basic, common sense talk on lymphedema, trying to define it in simple terms (no small feat when the literature was so poor - the definition at that time was a 2 centimeter difference between forearms - as if that was the only place one could have lymphedema!). Next, Diana presented some practical suggestions for nutrition that she had found helpful to her and several other women she knew. Finally, I wrapped up the session with some very basic information on exercise progression and then opened the floor for questions. The response was overwhelming. The participants were so grateful that their problem was finally acknowledged, even on such a basic level.

Twenty-four years later, although the medical management of lymphedema has come a long way, thanks in great part by the advocacy of Saskia Thiadens and the NLN, there is still much work to do. Basic and advanced research on the effects of exercise as a lymphedema risk reduction modality must be explored. The basic criticism of the precautions about exercise contained in the 18 Steps to Prevention of Lymphedema and other risk reduction guidelines is that they are "anecdotal" at the present time, due to the lack of controlled double-blind studies to prove their efficacy. Some medical professionals have taken the position that the individual with a limb at risk (or with lymphedema) should go ahead and pursue whatever exercise/activity they wish and "see what happens". Unfortunately, lymphedema is a chronic condition, which, presently, has no cure. While it is true that not all individuals who have had lymph node disruption (surgical or radiological) will develop lymphedema, until physicians can better predict who is at greater risk for lymphedema, a prudent approach to exercise is advisable. In the case of individuals with primary lymphedema or established secondary lymphedema, working up to a level of exercise that promotes fitness while avoiding exacerbating the lymphedema is a good goal.

I'm sure that some of you may have been told in the past that you should not exercise if you have lymphedema, or that certain types of exercise are contraindicated if you have lymphedema. This is not the case. I would like to review some basic principles of anatomy and physiology and pathophysiology of lymphedema and how these relate to exercise and lymphedema. Lymphedema occurs when there is an imbalance between lymph transport capacity and lymph load. After any surgical disruption or radiation treatment to a lymph node region, a state of latent lymphedema occurs. That is to say that the lymph transport capacity is reduced but it is still greater or equal to the lymph load. Acute/chronic lymphedema develops when that balance is shifted and lymph load exceeds the impaired lymph transport capacity. In the case of Primary Lymphedema, where there is a malformation/malfunctioning of the lymphatic transport system that results in a reduced lymphatic transport capacity, lymph load often exceeds that transport capacity, and progressive lymphedema develops over time.

Our lymphatic system, in addition to filtering out waste products, helps our bodies maintain fluid balance so that we are neither dehydrated nor edematous. 90% of the water component of our blood that perfuses the capillary network and nourishes our cells returns to the heart via the venous system. The 10% that is left behind in the tissues along with the extracellular protein that filters out of the capillaries, can only return to the heart via the lymphatics. That 10% can amount to up to 2 liters a day. While 2 liters may not seem like much, it adds up day after day, if there is impairment in lymph drainage. In addition, the extracellular proteins can only return to the central circulation via the lymphatic vessels. The diameter of these molecules is too large to fit into the openings in the vein walls - the openings in the lymphatic vessel walls are large enough for these protein molecules to enter easily.

So lymphedema is not only a problem of excess water remaining in the tissues, but of excess protein that remains in the tissues as well. Unfortunately, the body always moves for a state of balance so it actually tends to pour more water into the tissues to "dilute" this protein concentration - thus a vicious cycle develops. This problem is compounded by the fact that the white blood cells called macrophages, which are part of our immune response, do not work properly in the lymphedematous fluid. This is why anyone with lymphedema is at increased risk for infection in his or her affected limb.

What does all this have to do with exercise? A review of the acute and chronic effects of exercise is helpful to understand how the limb at risk or a lymphedematous limb might respond to various types of exercise. The acute responses to exercise include increases in heart rate, stroke volume, cardiac output, blood flow to active muscles, systolic blood pressure, arteriovenous oxygen difference, ventilation, oxygen uptake, and a decrease in blood pH and plasma volume. Chronic adaptations to exercise include biochemical changes in skeletal muscles, decreased resting heart rate, decrease in total body fat, blood lipids, and the density and strength of bone and connective tissue. During exercise, blood is redirected to the muscles. At rest, only 21% of the cardiac output goes to the muscles, compared with as much as 88% during exhaustive exercise. As the body heats up, an increasing amount of blood is directed to the skin, to conduct heat away from the body core.1 Remember that lymph transport has to be equal to or greater than lymph load. When you exercise, your muscles need extra blood to supply the oxygen needed for your muscles to do the work of the exercise. Extra blood flow means that extra water will remain in the extracellular spaces needing transport via the lymphatic system. The question is how much is too much? That is very individual. It is important that any exercise program be gradually progressed to avoid sprain/strain. More importantly, a slow progression allows the individual to monitor their affected limb or limb at risk for any sensation of aching or fullness that could indicate an overwhelming of the lymphatic system.

Exercise can increase the uptake of fluid by the initial lymphatics and enhance the pumping of the collecting lymphatics. In addition, exercise mobilizes the joints and strengthens the muscles of the involved limb/limbs/trunk quadrant, thus decreasing the risk of strain/sprain.2Exercise is best done with compression on the affected limb either from compression bandages or compression garments. The bandages provide a new "tight" skin for the muscles to contract against, assisting in pumping the lymph out of the extremity into the central circulation. When lymphedema exists, the remaining lymph vessels that are functioning are working double time to try to carry the load. These vessels become over dilated (stretched) and eventually, their walls can overstretch and fail, causing a worsening of the swelling. Wearing compression bandages/garments provides support to the skin and to the lymphatic vessels directly under the skin, called the superficial lymphatic network. It is these vessels that help to carry the load when the larger vessels have been cut away from the lymph nodes or have been damaged due to trauma or chronic venous disease, or in the case of primary lymphedema, when there are too few large lymph collectors in a region due to improper vessel/node development during fetal growth.

Of course, certain types of exercise are considered higher risk than others. For example, high speed activities like tennis, bowling and racquetball, place more stress on the upper limb while jogging, stair-climbing machines, downhill skiing, water skiing, football, soccer place more stress on the lower extremities or have higher injury risk than other activities such as swimming, brisk walking, and cycling. That is not to say that someone with lymphedema of the leg should not jog for exercise, or that the person with lymphedema of the arm and hand should not play tennis or golf. It is also important to know whether an individual was skilled at a sport/activity prior to their developing lymphedema. A sport-specific exercise program can be developed for the individual to build strength, flexibility and endurance in the muscle groups most used in that sport/activity. Ultimately, the decision to "play" should be an individual one, but an informed one.

Many men and women with lymhedema or a limb at risk want to work out with weights. A slow progression of light weights can be done safely and can allow an individual to develop good strength and power in any muscle group. The important thing to consider is whether you feel good after the exercise and how your affected limb reacts after you exercise. You must also consider your level of daily activity and modify accordingly - if you have had a particularly difficult day and your affected limb is more swollen, you may choose to do a different activity i.e. swim instead of walk, or you may realize that the best activity for that day is to rest with your limb elevated. The importance of deep abdominal breathing exercise should not be overlooked. Deep breathing enhances the pumping in the thoracic duct (the major lymphatic vessel draining the lower body and the left upper trunk/arm/hand).

A recent series of case reports published in the Journal of Surgical Oncology3 challenges the theory that vigorous upper body exercise is contraindicated for individuals who have had axillary dissection during surgery for breast cancer. The study followed a group of 24 women for 9 months. These women were recruited to participate in a training program to prepare for competition in the World Championship Dragon Boat Festival in Vancouver, British Columbia. Dragon Boat racing involves strenuous repetitive upper body exercise. 18-20 women paddle 40-60 foot boats for a distance of 500-650 meters. Circumferential measurements were collected on 20 of the 24 participants (limbs were measured at 4 places) pre training, at the start of the racing, and 7 months after the races. According to the authors, only two women, who had pre-existing mild lymphedema, had increases in their upper arms (5/8 inch) and none of the other participants developed lymphedema. One of the authors of the study, herself a breast cancer survivor participated in the program. The authors conclude that strenuous upper body exercise may not cause lymphedema or worsen a pre-existing lymphedema.

It is important to note that the participants in this study completed a two-month training program of stretching, strengthening, and aerobic exercises prior to engaging in the actual strenuous activity of Dragon Boat racing. Many individuals who undergo breast surgery/axillary dissection/radiation are not enrolled in supervised progressive exercise programs like the participants of this study. Providing structured, individualized exercise programs should be a goal of all centers that perform cancer surgeries. While I do not discourage individuals from participating in sports and exercise, I do caution them that they should consider themselves "athletes" in the "game" of life. As such, each individual should engage in a stretching/strengthening program to prepare them for full participation in whatever activity they choose.

References:

1. Nieman, David C. Exercise Testing and Prescription: A Health Related Approach, 4th ed. Mountain View, California, Mayfield Publishing Co., 1999: P, 190-205.2. Casley-Smith, Judith R, Casley Smith, John R. Modern Treatment for Lymphoedema, 5th ed. Adelaide, Australia, The Lymphology Association of Australia, 1997: p. 188-189.3. Harris, Susan R, Niesen-Vertommen, Sherri. Challenging the Myth of Exercise-Induced Lymphedema Following Breast Cancer: A Series of Case Reports. Journal of Surgical Oncology 2000; 74:94-99.

Lymphedema Therapy

Defective valves and abnormal mural cell recruitment underlie lymphatic vascular failure in lymphedema distichiasis

Tatiana V Petrova1, 8, Terhi Karpanen1, 8, Camilla Norrmén1, Russell Mellor2, Tomoki Tamakoshi3, David Finegold4, 5, Robert Ferrell4, Dontscho Kerjaschki6, Peter Mortimer6, Seppo Ylä-Herttuala7, Naoyuki Miura3 & Kari Alitalo1

1 Molecular/Cancer Biology Laboratory and Ludwig Institute for Cancer Research, Biomedicum Helsinki and Helsinki University Central Hospital, University of Helsinki, Haartmaninkatu 8, P.O.B. 63, 00014 Helsinki, Finland.

2 Dermatology Unit, St. George's Hospital Medical School, Cranmer Terrace, London, SW17 0RE, UK.

3 Department of Biochemistry, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan.

4 Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.

5 Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.

6 Department of Pathology, University of Vienna Medical School, 1090 Vienna, Austria.

7 A.I.Virtanen Institute, University of Kuopio, P.O.B. 1627, 70211 Kuopio, Finland.

8 These authors contributed equally to this work.Correspondence should be addressed to Kari Alitalo

kari.alitalo@helsinki.fi

Abstract

Lymphatic vessels are essential for the removal of interstitial fluid and prevention of tissue edema. Lymphatic capillaries lack associated mural cells, and collecting lymphatic vessels have valves, which prevent lymph backflow.

In lymphedema-distichiasis (LD), lymphatic vessel function fails because of mutations affecting the forkhead transcription factor FOXC2. We report that Foxc2-/- mice show abnormal lymphatic vascular patterning, increased pericyte investment of lymphatic vessels, agenesis of valves and lymphatic dysfunction.

In addition, an abnormally large proportion of skin lymphatic vessels was covered with smooth muscle cells in individuals with LD and in mice heterozygous for Foxc2 and for the gene encoding lymphatic endothelial receptor, Vegfr3 (also known as Flt4).

Our data show that Foxc2 is essential for the morphogenesis of lymphatic valves and the establishment of a pericyte-free lymphatic capillary network and that it cooperates with Vegfr3 in the latter process. Our results indicate that an abnormal interaction between the lymphatic endothelial cells and pericytes, as well as valve defects, underlie the pathogenesis of LD

Dagenais SL, Hartsough RL, Erickson RP, Witte MH, Butler MG, Glover TW.

Department of Human Genetics, University of Michigan, 4909 Buhl, Box 0618, 1241 E. Catherine Street, Ann Arbor, MI 48109-0618, USA.

sdagenai@umich.edu

The molecular events involved in lymphatic development are poorly understood. Hence, the genes responsible for hereditary lymphedema are of great interest due to the potential for providing insights into the mechanisms of lymphatic development, the diagnosis, prevention and treatment of lymphedema, and lymphangiogenesis during tumor growth.

Mutations in the FOXC2 transcription factor cause a major form of hereditary lymphedema, the lymphedema-distichiasis syndrome. We have conducted a study of Foxc2 expression during mouse development using immunohistochemistry, and examined its expression in lymphatics compared to its paralog Foxc1 and to Vegfr-3, Prox1 and other lymphatic and blood vascular proteins. We have found that Foxc2 is expressed in lymphatic primordia, jugular lymph sacs, lymphatic collectors and capillaries, as well as in podocytes, developing eyelids and other tissues associated with abnormalities in lymphedema-distichiasis syndrome.

PMID: 15465483

[PubMed - indexed for MEDLINE]

For further information:

Truncating mutations in FOXC2 cause multiple lymphedema syndromes.

Full Text Article

FOXC2 haploinsufficient mice are a model for human autosomal dominant lymphedema-distichiasis syndrome.

Full Text Article

Mutations in FOXC2 (MFH-1), a forkhead family transcription factor, are responsible for the hereditary lymphedema-distichiasis syndrome.

Full Text Article

Pretreatment lymphedema education and identified educational resources in breast cancer patients

Ridner SH.

Vanderbilt University School of Nursing, 461 21st Ave. South, Nashville, TN 37240, USA.

April 2006

OBJECTIVE:

In 1998, the American Cancer Society (ACS) Lymphedema Workshop, called for a three phase approach to patient lymphedema education: (1) pretreatment, (2) postoperatively, and (3) continuing education. The objectives of this study were: to compare recalled pretreatment lymphedema education before and after the 1998 ACS call; compare recalled lymphedema pretreatment education between women with and without breast cancer treatment-related lymphedema; and identify breast cancer survivors perceived sources of lymphedema education.

METHODS:

One hundred and forty-nine breast cancer survivors (74 with lymphedema and 75 without lymphedema) were asked: (1) Prior to having breast cancer treatment did anyone talk to you about your risk for lymphedema? If yes, who? (2) Prior to having breast cancer treatment did anyone talk to you about ways to decrease your risk for lymphedema? If yes, who? (3) If you want to learn more about lymphedema occurring after breast cancer treatment who would you ask or where would you look for information?

RESULTS:

Individuals with lymphedema consistently recalled receiving less education and a decline in recalled risk reduction education in the lymphedema group occurred after 1998.

DISCUSSION:

Barriers exist to the integration of ACS suggested pretreatment lymphedema educational protocols and risk reduction education may influence risk of developing lymphedema.

CONCLUSION:

Pretreatment lymphedema education may improve breast cancer survivor's recall of educational information received about lymphedema.

PRACTICE IMPLICATIONS:

Healthcare providers must be well versed about breast cancer treatment-related lymphedema and communicate this knowledge to patients on a consistent basis.

PMID: 16533679

[PubMed - in process]

* * * Editor's Note * * *

The sad reality is that some of the greatest opposition we face in pretreatment education of lymphedema is actually by oncologists themselves. Try getting educational booklets or phamphlets into an oncology clinic.

Lymphedema: Skin and Wound Care in an Aging Population

Michael J. King, MD, FACC, FACP; and Elisa G. DiFalco, CLT-LANA
Lymphedema Treatment Services, Inc., Lauderhill, Fla., USA.

May 2004

Lymphedema is a complex, unappreciated, and chronically progressive medical condition. Appropriate management requires a correct diagnosis and an understanding of the underlying pathophysiology. Fluid retaining conditions and mechanical problems both can lead to edema. Diuretic therapy may be correct for certain patients but can be harmful to others. Although lymphedema is not curable, it can be controlled and managed.1,2 Multiple medical and surgical subspecialties are usually involved in treatment.

Lymphedema is an increasing medical problem in this country. This is partly the result of medical personnel having little or no training or understanding of the condition. Consequently, patients are frequently left untreated or treated incorrectly. Increasing longevity leads to complications that are part of the natural history of lymphedema and aging. These complications never had time to develop to a point of clinical significance in the past. However, now they are seen in greater numbers. Likewise, dermatological problems increase with age. Edema in elderly patients with loss of elasticity, collagen, and vascular supply now result in problems, the frequency of which has not been seen in the past.

Most lymphedema in this country is the result of surgical treatment for a malignant disease. Because malignancy is increasingly curable, the latent potential for developing lymphedema is a growing medical problem.

Skin care always has been an important part of lymphedema treatment. With the skin changes of aging, even basic skin care and standard treatments such as manual lymph drainage, compression wrapping, and the use of stockings and sleeves are becoming difficult or impossible in patients with certain dermatological/medical disorders. Further complicating matters is the fact that skin ulcerations can have multiple causes. What is clear, however, is that skin lesions and ulcerations, regardless of origin, are difficult or impossible to heal in an edematus extremity. Yet therapy to relieve edema in the presence of wounds may not be possible, creating a "catch 22."

The lymphatic and venous systems are closely related and interact with each other. Problems in one area will inevitably lead to problems in the other. Both lead to a final common pathway. The target organ is the skin. Often, the result is the need for wound care, but hopefully advancement to this stage can be prevented.

The Lymphatic System

Lymphatic "circulation" is a misnomer. Normal circulation involves arteries and veins with the heart the driving force. In true circulation, the arteries deliver nutrients and oxygen to the tissues and capillaries on the venous side return blood back to the heart and lungs to be replenished. Without going into membrane physiology and physics at any length, fluid constantly shifts in and out of the standard circulation to interstitial spaces outside the vascular system. This is the result of physical laws involving pressure gradients, colloidal osmotic pressure, and a concept called ultrafiltration. To oversimplify things, Nature likes to equalize things across a barrier. Approximately 10% of the normal circulatory fluid filters into the interstitial spaces. Our bodies are endowed with additional vessels known as lymphatics. These vessels begin in the tissues. They act like garbage pails, picking up large protein molecules and other materials which, because of their size, are unable to filter back into the normal venous circulation. This is actually a half "circulation" that lies in close conjunction with the venous system; it is quite intricate and complex. The fluid movement in the lymphatic system is not dependent on the pumping of the heart. The smaller lymphatics lead to larger ones that have smooth muscle and neurological connections.

Lymphangions are a segment of the lymphatic system. These vessels have valves and stretch receptors that contract and push fluid toward the heart. In addition, pulsations from nearby arteries and muscle contractions help propel lymphatic fluid back to the heart. On its course, lymphatic fluid passes through a series of lymph nodes, is purified, and ultimately returns to the general circulation.

Normally at rest, flow in the lymphatic system is minimal, but if the lymphatic workload is increased, the lymphatic circulation is capable of increasing its activity; in this manner, it acts as a self-contained pacemaker. Aside from its garbage pail nature, the lymphatic system performs a central immunological function. This is beyond the scope of this article.

Lymphedema, then, can develop for two main reasons: 1) disease, malfunction, or maldevelopment of the lymphatic system that renders it unable to handle a normal lymphatic load [low output]; or 2) a normal lymphatic system that is overwhelmed, usually the result of other medical conditions. In either case, the result will be increased protein and fluid in the interstitial spaces and the inability to absorb this fluid. Because this fluid is high in protein and other large molecules, it tends to draw additional fluid into these extra cellular spaces. The end result is edema, and this scenario sets in motion an inflammatory response leading to fibrosis and disruption of vascular integrity. The ultimate victim of all of this is the skin, not to mention the patient.

Lymphedema.

Edema, regardless of origin, ultimately affects the microcirculation. Tissue oxygenation and nutrition are effected. Changes in skin color are well known and common. With lymphedema, increased fibrosis, hardening of the skin, lobulations, and changes typical of elephantiasis occur. Blistering, weeping, and breakdown of the skin also are common and lead to cellulitis, further damaging the lymphatic system and microcirculation. In summary, this becomes a self-perpetuating nightmare. When skin breaks down and ulceration develops, especially in the presence of other diseases, the viability of an extremity can be threatened. Problems do not normally develop to this extent in typical lymphedema (either primary or secondary involving the upper extremities) except in the presence of malignant lymphedema. With venous insults such as axillary vein thrombosis, edema may develop, but the swelling is usually temporary. The same is apparently true for other upper extremity surgery involving the venous system alone, where edema of the upper extremity develops from disruption of the lymphatic system.3

The same is not true for skin disorders and ulcerations involving the lower extremities. The difference between arterial, venous, and stasis and pressure ulcers should be relatively easy to diagnose with a proper history and physical examination. As previously noted, it is medically important to determine the underlying reason for edema and ulcerations. Plastic surgical procedures including liposuction also can lead to lymphedema. In older people, especially those with "thin skin," ulceration of the skin can be difficult to heal. In these cases, even minimum trauma caused by compression stockings can lead to skin damage, making treatment difficult. Both edema therapy and preventive skin care are needed; creating a balance between both therapies can be challenging because, at times, they can be contradictory.

Chronic venous insufficiency (CVI) is a common cause of edema and ulceration of the skin. Lymphatic abnormalities exist in patients with CVI.4,5 Lymphedema is always present in advanced stages of CVI, and theories regarding the pathogenesis of skin ulceration in patients with this disorder are numerous.4,5 Skin grafts are unlikely to work on an edematous area. MLD, a gentle manual treatment that improves the activity of the lymph vessels and re-routes the lymph flow around the blocked areas into more centrally located lymph vessels that drain into the venous system, can reduce the pain, fibrosis, and postoperative morbidity in postsurgical cases.6 The bottom line is that ulcerations of the skin are not likely to heal in the presence of edema for whatever reason. Again, skin care, wound care, and edema must be addressed at the same time. While the authors' emphasis is on lymphedema, skin care always has been an important part of lymphedema treatment.

Treatment

Over the years, the authors have tried to emphasize the need for skin care in their patients. With the aging population, low pH moisturizing lotions and standard wound care methods are proving to be inadequate in patients whose skin has broken down or has that potential; hence, preventing the use of standard lymphedema treatment in many patients.

Recently, soft silicone technology products of various kinds (eg, Tendra, Mölnlycke Health Care, Newtown, Pa.) have been used according to patients' needs, type of wound, and amount of skin drainage Wound adherence has not been a problem and these products are easy to use. They have enabled clinicians to perform CDT, a comprehensive form of treatment for lymphedema involving physical techniques, compression wrapping, and patient education, as well as MLD, wrapping over the skin dressings. This has enabled lymphedema treatment; thereby, promoting wound healing while treating skin ulcerations. Silicone-based products also have been used in jeopardized skin as a preventive measure in conjunction with the usual wrappings and treatment for lymphedema. Thus far, this appears to be an effective approach.

Conclusion

Although patient numbers are small at the authors' facility and their experience may be somewhat anecdotal, lymphedema treatment in conjunction with soft silicone technology appears to be a workable combination and merits further investigation. - OWM

Acknowledgment

The authors are grateful to Anita King and Leora Krupnick for their invaluable assistance in preparing this article, as well as Joachim Luther and The Academy of Lymphatic Studies. They especially thank Robert Lerner, MD, who has been and continues to be an inspiration to all.Addressing the Pain is made possible through the support of Molnlycke Health Care, Newtown, Pa.

References

1. King MJ. Lymphedema - the role of the physician. Contact the author.2. King MJ, DeFalco E. Multiple radio tapes and articles. Contact the author.3. Foldi M, Foldi E, Clodius. The lymphedema chaos. Ann Plast Surg. 1989;22:505.4. Tehrani H. International Varicose Vein Congress. Miami Vein Center. Key Biscayne, Fla. September 21, 2003.5. Hartmann M. CVI. In: Weissleder, Schuchardt. Lymphedema - Diagnosis and Therapy. Viavital Verlag GmbH; 2001:266-2826. Cass LA, De Poli P. Manual Lymphatic Drainage Therapy: An Integral Component of Post-Operative Care in Plastic Surgery Patients. Abstract lecture. Northwestern University of Medical School.

Ostomy Wound Management

Mapping of primary congenital lymphedema to the 5q35.3 region.

A L Evans, G Brice, V Sotirova, P Mortimer, J Beninson, K Burnand, J Rosbotham, A Child, and M Sarfarazi

Cardiological Sciences, St.George's Hospital Medical School,London, United Kingdom.

Abstract

Primary lymphedema is a chronic tissue swelling, most frequently of the lower limbs, resulting from deficient lymphatic drainage. The variability of the affected phenotype, incomplete penetrance, lack of large families, and possible genetic heterogeneity have hampered the identification of causative genes until now. We carried out a genomewide search, using a four-generation North American family with dominantly inherited primary congenital lymphedema (PCL), otherwise known as "Milroy disease," or "hereditary lymphedema type I" (MIM 153100). Linkage to markers from the 5q35.3 region in this and four additional, British families was established. A minimum of 79 directly scorable haplotypes (37 affected) in five families conspicuously segregated with the most telomeric region of 5q35.3, thus suggesting a major locus for PCL in this vicinity. No recombination was observed with D5S408 (Z = 10.03) and D5S2006 (Z = 8.46) with a combined multipoint score of 16.55. While D5S2073 and WIAF-2213 defined the upper centromeric boundary, no recombinants were obtained for the last telomeric marker of D5S2006. Four unaffected subjects were identified as gene carriers and provided an estimated penetrance ratio of.84 for this condition. A few of the positionally mapped genes in the 5q35 region that may potentially be involved in the etiology of this condition are CANX, FGFR4, HK3, and hnRPH1.

PubMed Central

Full length article

Transient versus Chronic Lymphedema

Transient lymphedema is a temporary condition that lasts less than 6 months and is associated with pitting edema with tactile pressure and lack of brawny skin changes.[1]

The following factors may place the patient at risk for acute-onset, transient lymphedema:

Surgical drains with extravasation of protein into the surgical site.
Inflammation following injury, radiation, or infection leading to increased capillary permeability.
Immobility of the limb(s) that results in decreased external compression by the musculature.
Temporary absence of collateral lymphatics.
Proximal venous occlusion by thrombosis or phlebitis.

Reversal of equilibrium at the capillary bed that results in accumulation of third-space fluid.

Chronic lymphedema is the most difficult of all types of edema to reverse, due to the nature of its pathophysiology. A cycle is started, in which the deficient lymphatic system of the limb is incapable of compensating for the increased demand for fluid drainage.

This condition may occur subsequent to any of the following:

Tumor recurrence or progression in the nodal area.
Infection and/or injury of lymphatic vessels.
Immobility.
Radiation injury to lymphatic structures.
Surgery.
Unsuccessful management of early lymphedema.
Venous obstruction due to thrombosis.

* * Editor's note:

(1) It is imperative to understand that any transient lymphedema can become chronic and permenant without proper intervention. Therefore, even if a physcian believes a patient has "transient" lymphedema, they should be referred to a certified lymphedema therapist for an evaluation and treatment.

(2) Chronic lymphedema can be hereditary and/or congenital. It is also associated with various conditions that involve lymphatic dysplaysia. This lymphedema is also referred to as primary.

Early in the course of developing lymphedema, the patient experiences soft, pitting edema that may be easily improved by limb elevation, gentle exercise, and elastic support. Continual and progressive lymphostasis, however, causes dilation of the lymph vessels and backflow of fluid to the tissue beds. Collagen proteins accumulate, further increasing colloid osmotic tissue pressure, leading to enhanced fluid flow from the vascular capillaries into the interstitial space. The stasis of fluid and protein stimulates inflammation and macrophage activity as the body attempts to degrade the excess proteins. Fibrosis of the interstitial connective tissue by fibrinogen and fibroblasts causes the development of the brawny, stiff, nonpitting lymphedema that no longer responds to elevation, gentle exercise, or elastic compression garments. Chronic lymphedema gradually becomes nonpitting.

Lymphedematous tissues have lower oxygen content, a greater distance between lymph vessels due to fluid accumulation and swelling, impaired lymphatic clearance, and depressed macrophage function, rendering patients at increased risk of infection and cellulitis. Since there is no other route for tissue protein transport, treatment for patients with advanced lymphedema with chronic fibrosis is more difficult than when treated earlier. Additionally, once these tissues are stretched, edema recurs more readily.

Generalized lymphedema may also occur subsequent to hypoalbuminemia with low plasma oncotic pressure due to the following:

Inadequate oral nutrition (secondary to anorexia, nausea, vomiting, depression, chemotherapy).
Decreased intestinal absorption of protein or abnormal protein synthesis/anabolism.

Protein loss due to leakage of blood, ascites, effusions, or surgical drains.

Contributing medical conditions leading to hypoalbuminemia (e.g., diabetes, kidney malfunction, hypertension, congestive heart failure, liver disease).

Wrong Diagnosis.Com

Acute-Onset versus Insidious-Onset Lymphedema

Secondary lymphedema may be categorized by its chronicity. Four patterns of acute lymphedema have been identified. The first occurs within a few days after surgery as a result of the cutting of lymphatic channels or injury to or manipulation of the subclavian lymphatic trunks or the associated subclavian veins. It is usually transient and mild, responding to limb elevation and muscle pumping of the associated limbs (e.g., making a fist and releasing it) within 1 week of onset. The affected area may be warm and slightly erythematous, but it is generally not painful.

A second type of acute lymphedema may occur within 6 to 8 weeks postoperatively, possibly as a result of acute lymphangitis or phlebitis. There is no associated venous thrombosis in these cases. This pattern of lymphedema may also be seen during the course of radiation treatment of a limb or its associated lymphatic drainage route. The affected area is tender, warm or hot, and erythematous. This type of lymphedema can usually be successfully treated with limb elevation and anti-inflammatory medication, although more involved treatments may be necessary. The first 2 acute forms do not necessarily portend chronic swelling after their resolution.

A third type of acute lymphedema is an erysipeloid form, occurring after an insect bite, or minor injury or burn. It is often superimposed on a chronic edematous limb. The affected area is erythematous, very tender and hot. This form of edema often requires limb elevation and antibiotics. Compression pumping or wrapping is contraindicated during acute stages of infection. Many clinicians will permit treatment once severe erythema or blistering has resolved. Mild erythema can persist following an infection.

The fourth and most common type of lymphedema is usually insidious and is not always associated with erythema. Discomfort of the skin or aching in the proximal segments (neck/shoulders for upper extremity, lumbar spine/hips for lower extremity) may be noted due to stretch of the soft tissues or muscular overuse and postural changes caused by increased limb weight. This type has a variable onset and is frequently apparent 18 to 24 months after surgery. It may appear a few months or many years after cancer treatment.

Lymphedema - WrongDiagnosis.com