Is lymphedema a gender issue?

Lymphedema unrelated to cancer occurs more often in women than in men. Eighty-three percent of primary lymphedema (lymphedema that develops in the absence of iatrogenic or other sources of lymphatic compromise) patients are female . This estimate must be interpreted as imprecise because definitive epidemiological work is lacking. However, anecdotal clinical experience corroborates the preponderance of women among lymphedema patients. This phenomenon may be partially explained by the higher prevalence of obesity in women . As suggested above, an elevated body mass index is a risk factor for lymphedema . Obese women without histories of lymphatic compromise are frequent lymphedema patients. Recent projections anticipate a continued rise in the prevalence of female obesity, which will undoubtedly have an impact on the future composition of lymphedema patients .

Assessing lymphedema risk

All patients who have undergone lymph node resection or irradiation are at some risk of developing lymphedema. Generally, lymphedema risk increases directly as treatments become more aggressive and anatomically disruptive . Each patient’s “at risk” territory depends on the lymphotome or lymphotomes affected by their treatment. A lymphotome is the territory drained by a superficial lymph node bed. Fig. 1 shows the body’s six superficial lymph node beds (ie, a pair of cervical/supraclavicular beds, a pair of axillary beds, and a pair of inguinal beds) and their associated lymphotomes. Breast cancer patients are solely at risk in the axillary lymphotome on their affected side. The axillary lymphotome encompasses the ipsilateral arm, breast, and upper truncal quadrant. Patients treated for gynecological cancers potentially have much more extensive territory at risk. Their pelvic and peri-aortic lymph nodes may have been resected and irradiated. These deep nodes receive lymph from both superficial inguinal beds, which drain the lower extremities, lower truncal quadrants, and external genitalia. Due to extensive compromise of these deep lymph nodes, treatment of gynecological cancers places the entire lower half of the body at risk for lymphedema. Despite the potential for widespread lymphedema, patients generally present with lower-extremity swelling.

Three pairs of lymph node beds receive lymph from the body’s six lymphotomes.

Many factors have been studied with regard to lymphedema risk. The contribution of obesity and weight gain to lymphedema development has been previously mentioned. Of note, obesity increases risk of lymphedema progression and refractoriness to conventional therapy . Venous insufficiency and recurrent soft tissue infections may harm the lymphatic system and undermine lymph drainage . The underlying mechanisms are imperfectly understood. Medical comorbidities, including diabetes, hypertension, congestive heart failure, and autoimmune conditions, have not been implicated in lymphedema despite considerable epidemiological scrutiny. Vocational and avocational pursuits that require vigorous and repetitive upper-extremity use do not appear to increase lymphedema risk in breast cancer patients . Similar studies have yet to be conducted with patients who have developed or are at risk of lower-extremity lymphedema. It has been suggested that postoperative complications, such as infection, axillary web syndrome, and seroma or hematoma formation, increase lymphedema risk. Prospective cohorts of sufficient size have not been followed to definitively address these concerns.

Assessing lymphedema risk

All patients who have undergone lymph node resection or irradiation are at some risk of developing lymphedema. Generally, lymphedema risk increases directly as treatments become more aggressive and anatomically disruptive . Each patient’s “at risk” territory depends on the lymphotome or lymphotomes affected by their treatment. A lymphotome is the territory drained by a superficial lymph node bed. Fig. 1 shows the body’s six superficial lymph node beds (ie, a pair of cervical/supraclavicular beds, a pair of axillary beds, and a pair of inguinal beds) and their associated lymphotomes. Breast cancer patients are solely at risk in the axillary lymphotome on their affected side. The axillary lymphotome encompasses the ipsilateral arm, breast, and upper truncal quadrant. Patients treated for gynecological cancers potentially have much more extensive territory at risk. Their pelvic and peri-aortic lymph nodes may have been resected and irradiated. These deep nodes receive lymph from both superficial inguinal beds, which drain the lower extremities, lower truncal quadrants, and external genitalia. Due to extensive compromise of these deep lymph nodes, treatment of gynecological cancers places the entire lower half of the body at risk for lymphedema. Despite the potential for widespread lymphedema, patients generally present with lower-extremity swelling.

Three pairs of lymph node beds receive lymph from the body’s six lymphotomes.

Many factors have been studied with regard to lymphedema risk. The contribution of obesity and weight gain to lymphedema development has been previously mentioned. Of note, obesity increases risk of lymphedema progression and refractoriness to conventional therapy . Venous insufficiency and recurrent soft tissue infections may harm the lymphatic system and undermine lymph drainage . The underlying mechanisms are imperfectly understood. Medical comorbidities, including diabetes, hypertension, congestive heart failure, and autoimmune conditions, have not been implicated in lymphedema despite considerable epidemiological scrutiny. Vocational and avocational pursuits that require vigorous and repetitive upper-extremity use do not appear to increase lymphedema risk in breast cancer patients . Similar studies have yet to be conducted with patients who have developed or are at risk of lower-extremity lymphedema. It has been suggested that postoperative complications, such as infection, axillary web syndrome, and seroma or hematoma formation, increase lymphedema risk. Prospective cohorts of sufficient size have not been followed to definitively address these concerns.

Primary prevention

The success of researchers and breast cancer patient advocates in bringing lymphedema to popular attention has spurred surgical innovations that reduce axillary lymph node compromise. Sentinel lymph node biopsy (SLNB) represents the most recent and significant step forward in this effort. In brief, SLNB involves the injection of radioactive tracer and blue dye into the soft tissue surrounding a breast tumor. When the axillary lymph node bed is surgically exposed, visual inspection and a hand-held gamma probe allow identification of lymph nodes that have taken up both tracer and dye. These “sentinel lymph nodes” are then resected. Sentinel lymph nodes are subjected to rigorous pathological scrutiny. If metastases are not detected, no additional lymph nodes are removed. The absence of cancer cells in the sentinel lymph nodes supports the inference that cancer has not spread beyond the primary tumor. Further anticancer treatments are planned accordingly.

SLNB has become the standard approach to the initial axillary surgical sampling. SLNB represents a dramatic advance in that it reflects prioritization of patients’ long-term functional status and morbidity among surgical outcomes. SLNB apparently has significantly reduced the incidence and severity of lymphedema among breast cancer survivors. Initial reports of zero incidence have emerged as overly optimistic . Even so, the current best estimate of a 7% incidence at 6 months postoperation is an improvement over prevalence rates as high as 68% after full axillary lymph node dissection and irradiation .

One of the most challenging aspects of lymphedema is that by the time swelling becomes clinically obvious, significant changes have already occurred in the lymphatic system and interstitium. Anecdotal evidence suggests that these changes may be irreversible and, once established, preclude restoration of normal lymphatic homeostasis . Several technologies show promise of detecting lymphedema in its preclinical phase. These are bioimpedance and high-frequency ultrasound . However, these remain largely experimental and current evidence does not support their integration into clinical practice.

An additional impediment to primary prevention is the lack of empirically based models of lymphedema pathogenesis. Many primary-risk–reducing strategies have been rigorously endorsed . Some make good theoretical sense and are aligned with general health recommendations (eg, avoiding sunburns and trauma to the at-risk body part). Other strategies, such as avoidance of exercise and repetitive upper-extremity use (in the case of breast cancer), have potentially adverse consequences for patients’ quality of life and general well-being. Evidence suggests that exercise may reduce patients’ risk of breast cancer recurrence by as much as 50% . Further, well-designed trials increasingly suggest that exercise, when properly performed, may protect against lymphedema . Thus, advice against exercise or other activities with quality-of-life implications must be carefully weighed in light of each patient’s overall clinical picture and the shifting evidence base.

Additional common risk-reduction approaches include prophylactic use of a compression sleeve, avoidance of needle sticks and blood-pressure cuffs, avoidance of manicures, and use of protective clothing (eg, gloves) while engaging in tasks that may compromise skin integrity . Endorsement of any approach to risk reduction, given the tenuous evidence base, should depend on a number of factors. These include patients’ lymphedema risks, activity profiles (eg, frequency and duration of air travel), and anxiety levels regarding lymphedema. Given the previously mentioned challenges to accurate lymphedema-risk prediction, estimates are inevitably imprecise. However, patients who have undergone extensive surgical nodal clearing and irradiation are unquestionably at higher risk.

Thanks to expanded cancer survivorship services and the abundance of Web-based information, patients have ever-increasing awareness of their lymphedema risk. Inaccurate and sensational portrayals of lymphedema and lymphedema risk represent a down side to this generally desirable trend. Confronted by photos of advanced elephantiasis (stage III lymphedema), patients may experience understandably high levels of anxiety and inadvertently cause harm in their zeal to prevent lymphedema. Providing patients with accurate lymphedema-risk prevention information may, by relieving their anxiety, do much to improve their quality of life while potentially reducing their lymphedema risk very little .

The following paragraph offers a few pointers about the pros and cons of prophylactic compression garments. Many patients are instructed to obtain and wear compression garments during provocative circumstances (eg, air travel) . Far from being a global recommendation, unmonitored garment use can cause significant problems. Garments should always be provided by a formally trained and experienced fitter. Poorly fit sleeves can trigger lymphedema. Constriction at the proximal band and the flexed elbow may severely impede lymph flow. Sleeves should always be dispensed with a glove or gauntlet. Compressing the arm may interrupt lymph drainage from the hand and potentially create a gradient that favors fluid accumulation in the hand. The author has managed patients whose hand lymphedema was unfortunately triggered by sole use of an overly tight sleeve without hand compression.

Though less problematic, proper fit remains a concern with lower-extremity garments. The issue of tight proximal bands is similar, compounded by the tendency of excessively long stockings to be rolled up or bunched and form a tourniquet. Patients should never fold over the proximal portion to reduce length. Additionally, most off-the-shelf stockings are designed for use in venous stasis disease, which generally spares the feet. Compression in most off-the-shelf stockings, therefore, begins at the distal calf and leaves the feet relatively uncompressed. A gradient may be established that favors fluid accumulation over the dorsal feet. Compressive footwear may offset the tendency for dorsal swelling, yet patients should remain vigilant.