Lymphedema in Cancer

Facts
Arteries arterioles capillaries venules veins. In contrary, peripheral lymphatics dead ended. Originate in distal-most tissues of skin, muscles, visceral organs, lung, and intestine. Lie within neurovascular bundles. Lymph flow centripetal (distal proximal). Lympahtics not present in
 Avascular - epidermis, hair, nails, cartilage & cornea  Vascular brain & retina

Anatomy
Lymphatic transport system
I. Superficial system drains skin & SC tissues. II. Deep subfascial - drains muscles, joints, synovial sheaths & bones III. Visceral - drains small intestine, spleen, liver, thymus & lungs.

Collecting vessels
Prelymphatic tissue channels
 Tiny vascular structures  No endothelium  Collect lymph

Lymph capillaries
 Valveless  Single cell layer of continuously overlapping endothelial cells.  Fibrous strands anchor to surrounding tissue fibrils  Regulate flow by alternatively stretching and relaxing

Lymph capillary

Collecting vessels
Lymph precollectors
 1 layer of muscle cells & collagenous fibers.  Unicuspid/ bicuspid valves maintain centripetal flow.  Dispersed 6 to 20 cm apart  Initiate lymphatic flow

Lymph collectors
 Main transporter of lymph  Resemble vascular structures
 Intima endothelial lining  Media muscle cells & collagen fibers  Adventitia collagen fibers extending into tissues.

Collecting vessels
Lymph collectors
 Nourished by vasa vasora  Part lying between valves lymphangion
 Sympathetic & parasympathetic supply spontaneous contractions.

Lymph nodes
Lymph nodes
 Total 600 700, most in abdomen & neck.  Kidney shape  Many afferent lymph vessels enter from convex surface.  1 or 2 efferent lymphatic vessels exit from hilum  Arterioles, venules & nerves enter and exit from hilum

Lymph nodes
Lymph nodes
 Concentrate lymph to half  Filter high molecular proteins, fats, cellular debris, foreign organisms, viruses & bacteria.  Macrophages, plasma cells & lymphocytes initiate immune response.  Lymphocyte, monocyte maturation.

Lymph ducts
Lymph ducts
 Largest transport structures  As progress, space between valves thickens & nerve endings . , tunica media

Functions of lymphatic system

Transport lymph from periphery to large veins of neck. Maintain homeostasis
 Fluid volumes  pH  Electrolytes

Immune regulation

Lymph/ Interstitial fluid

Forms in inter-cellular space Serum = Blood (RBCs + platelets) Contents
 96% Water +  proteins, lipids, carbohydrates, enzymes, glucose, urea, hormones, dissolved gases (carbon dioxide, oxygen), cells (lymphocytes, macrophages), unwanted toxins, bacteria and viruses, cellular debris, and other bodily wastes  Colloids - sodium, potassium, chloride, calcium, phosphorous, magnesium, and zinc or copper.

Edema
Amount of interstitial fluid increases and the area becomes swollen with excess fluid. Increase fluid discharge
 From the arteriovenous capillaries, such as trauma or infection

Decreases its reabsorption into lymphatics

Causes of lymphedema
Primary
 Lymphatics cannot propel lymph  Alteration/ deficiency within lymphatic collecting or transport systems.
     Milroy disease (Hereditary Lymphedema Type I) Meige disease (Hereditary Lymphedema Type II) Lymphedema praecox Lymphedema tardum Lymphangioma

Causes of lymphedema
Secondary lymphedema
 Infection
 Filariasis (MC), erysipelas, lymphogranuloma venerum, scrofula.

 Inflammation
 SLE, RA, Graves disease.

 Chronic venous insufficency

 Venous disease in legs chronic damage to veins and their valves valve failure reflux pressure on normal veins and damage to surrounding tissues and lymphatics

Causes of lymphedema
Secondary lymphedema
 Hypoalbuminemia
 albumin osmotic (oncotic) pressure reabsorption of interstitial fluid into venous capillaries chronic B/L swelling  Glomerulonephritis, nephrotic syn., extensive burns, kwahshiorkar, liver cirrhosis.  NSAIDs, antihypertensives, hypoglycemics, etc.

 Drug induced  Cancer

Lymphedema in cancer
Lymphadenectomy inguinal, iliac, axillary LN (MC non-infectious chronic unilateral swelling) Radiation to LN chronic unilateral (U/L) swelling Surgery of prostate, uterus or cervix B/L swelling Recurrent/ metastatic malignancy Hodgkin & non-hodgkin lymphoma

History
U/L, painful, duration hours to days.
 Acute DVT, cellulitis, compartment syndrome.

U/L, painless, over weeks to months.

 Chronic Lymphedema, soft tissue/ vascular tumors, AV fistulas, chronic venous insufficency.

B/L, over weeks to months.

 CHF, nephrotic syn., glomerulonephritis.  Malignancy in pelvis, abdomen or retroperitoneal space.  Advanced ca. prostate, ovary, pelvic tumors

Testing
Lymphedema
 Lymphoscintigraphy Radioisotope-labeled colloid injected into web space between first and second toes. Gamma camera measures colloid movement as it travels toward proximal lymph nodes If slow progress of radioisotope, compared with normal lower limb - hypoplasia of peripheral lymphatics (primary lymphedema). If radioisotope escapes from main lymph channels, especially into skin (dermal backflow) - lymph reflux (secondary lymphedema with proximal lymph obstruction).

Testing

Testing
Lymphedema
 Lymphangiography
 Rarely done  Radio-opaque lipiodol injected directly into peripheral lymph vessel x-rays monitor its proximal progress.

 CT/ MRI
 Subcutaneous honeycomb pattern  MRI superior also detects excess fluid

Testing

Testing
VTE
 D-dimer for DVT.  U/S for deep, perforator, and superficial venous systems of legs.  Contrast venography for pelvic or abdominal thrombus  CT for pelvic malignancies/ retroperitoneal fibrosis.  Ankle brachial pressure index (APBI) arterial insufficiency in legs of old patients and diabetics

Staging
5 Goals to accomplish
Evaluate and identify symptoms and possible etiology. Determine duration, extent and severity of disease. Outline medical intervention and expected outcome. Help patients understand disease, possible management options, anticipated results, and promote compliance.  Help insurance companies ascertain possible expenses.    

Staging
Revised ISL (International Society of Lymphology) Consensus Document 2001.
 Stage I - early accumulation of fluid relatively high in protein content and which subsides with limb elevation.  Stage II - limb elevation rarely reduces tissue swelling and pitting is manifest.  Stage III - lymphostatic elephantiasis - skin does not pit with trophic skin changes as acanthosis, fat deposits and warty overgrowths.

Consensus document 2003

 Stage 0 Latent/ subclinical.

Staging

Stage 1

Stage 2

Stage 3

Lymphedema management
Comprehensive Decongestive Therapy (CDT) by ISL. Components
     Manual lymph drainage Specialized bandaging Exercise Skin care Self management program

Lymphedema management
CDT goals
    Improve integrity of skin, connective tissues. Reduce/ eliminate infections Reduce edema Facilitate patients ability to manage themselves

Lymphedema management
CDT 2 phase treatment
 Phase 1 (by trained health care professional)
 manual lymph drainage  skin care (including wound care if indicated)  bandaging (specialized)  exercise (in bandages)  compression garment (if appropriate)

 Phase 2 (by patient)

 skin care  manual lymphatic drainage (as needed)  daytime compression garment, nighttime bandaging  exercise (in bandages or garment)  support groups

Manual lymph drainage

Effects of manual lymph drainage on lymphatics
    lymph transport capacity volume of lymph fluid transported proximally frequency of lymph vessel contractions pressure in lymph collector vessels Redirect natural flow patterns toward collateral vessels, anastomoses, and uninvolved lymph node regions arteriolar blood flow

Manual lymph drainage

Recruits functioning lymph vessels and nodes closest to regions not adequately performing. Regardless of site of insufficient flow, manual work on neck, back, abdomen & uninvolved inguinal and axillary LN. Begin from contralateral trunk area towards congested area. Then continue to move from involved area to uninvolved area. Be light, slow & precise.

Manual lymph drainage

No deep strokes as in standard massage. Rather, a specified number of light pressure strokes without friction that directionally stretch tissue. Each session lasts minimum of 45 to 60 min.

MLD techniques
Stationary Circles Strokes in continuous spirals with fingertips typically over neck, face and LN.

Pump Technique Place palms on skin, make oval strokes with fingers and thumbs to encourage lymph flow.

MLD techniques
Rotary Technique Massage skin in circular motions with palms facing down. Wrists used to apply and lessen stroke pressure.

Scoop Strokes Palms face up, fingers remain outstretched so that hands cupped to resemble a scoop. Twisting strokes to skin encourage waste disposal.

Skin care
To avoid/ eliminate fungal and bacterial infections. Protein-rich fluid accumulates in lymphedematous tissues, serves as culture medium for pathogens circulating within body or entering through skin lesions. Skin conditions in lymphedema
 Dry skin, hyperkeratosis, lipodermatosclerosis, fungal infections, lymph fistulas, eczema, chronic ulcerations.

Wound care
When integrity of skin compromised. Compression aided care.

Bandaging
Skin elasticity partially lost tissue hydrostatic pressure by external support. Support be continuous until volume reduction stabilizes and tissues remodel with improved functional lymphatic capacity.

Bandaging
After manual lymph drainage, skin cleansed and protected with moisturizer. If ulcerations, place protective dressing that absorbs exudate. A specific combination of padding, foam, protective gauze & short-stretch bandages applied in precise layers. Bandages be worn continuously except for time required to cleanse, treat, or rewrap limb. Teach the patient/ attendant.

Bandaging
Effects on lymphatic system
      Support for tissues with lost elasticity. muscle pump efficiency during activity. rate of ultrafiltration. facilitates colloidal protein reabsorption. softens fibrotic tissue with localized pressure. provides mild in tissue pressure, assisting lymph vessels to empty.  hydrostatic pressure gradient between blood and lymphatic tissues, preventing refilling of interstitium with fluid.

Bandaging

Types of bandages
Short stretch type
    Little or no stretch Form envelope/ cocoon around limb In resting state, minimal but constant compression Compression only during exercise as muscles expand and press against wrap.
 Exercise important for optimum effect.

 Worn at night.

Types of bandages
Long stretch type
 Highly elastic extend to 3 resting length.  High resting pressure continuous compression on limb.  Compressive force during exercise due to stretch caused by muscle expansion.  Not recommended at night because high resting pressure.
 Compromises arterial circulation and already compromised tissues.

Exercises
Can be performed with bandages Promote emptying of affected lymph regions Assist functioning lymphatics to work more efficiently cardiovascular function, muscular strength, functional capacity, and endurance. Consider limitation in joint range of motion, muscle strength, and posture or gait deficits while developing exercises.

Compression garment
Worn at end of intensive treatment phase if compromised limb/ body part reached normal or near normal size. Most appropriate in earliest stage/ at risk. Affect lymphatics by
 Maintain hydrostatic pressure that prevents refilling of interstitial space with lymph.  Preserve long-term reductions of limb circumference achieved by CDT.  Continue softening of fibrotic tissues initiated during treatment phase.

Compression pumps
Pneumatic Effectiveness debatable. Intermittent/ sequential compression Capillary filtration. Effective in palliative care.

Others
Nutritional counselling
 Obesity can lymphedema  Advice and strengthen lifelong lifestyle changes.

Psychosocial
 Encouraging patient and attendant participation compliance.  Address concomitant health concerns
 depression, isolation, loneliness, anxiety, poor coping skills.

Surgery
Selection criteria
 Failed satisfactory control of lymphedematous process/ prevent disease progression during a year of vigorous medical management.  Serious commitment to a lifetime of maintenance.  Stage III with profound soft tissue changes, hardened fibrosclerotic tissues with distortion, disfigurement, and/or elephantiasis.  Recurrent sepsis >3 times during a year even with adequate antibiotics.

46 y woman had surgery and radiation for uterine cancer. Lymphedema in left leg confirmed by lymphoscintigram, showing marked dermal backflow.

 First association between malignancy & cancer Armand Trousseau. Succumbed to gastric cancer developed thrombophlebitis in upper arm. Trousseasus syn. any VTE in solid/ hematoligical malignancies. VTE in cancer
 Symptomatic 10 to 15%.  Autopsy 50%.

10 to 15% patients with idiopathic TE develop cancer in 2 years.

 Highest incidence cancers

     Lung Pancreas Stomach Colon Ovaries