Abstract

Preoperative Assessment of Upper Extremity Secondary Lymphedema

Itay Wiser , Babak J. Mehrara, Michelle Coriddi, Elizabeth Kenworthy, Michele Cavalli, Elizabeth Encarnacion and Joseph H. Dayan. Cancers 2020, 12, 135.

Introduction: The purpose of this study was to evaluate the most commonly used preoperative assessment tools for patients undergoing surgical treatment for secondary upper extremity lymphedema.

Methods: This was a prospective cohort study performed at a tertiary cancer center specializing in the treatment of secondary lymphedema. Lymphedema evaluation included limb volume measurements, bio-impedance, indocyanine green lymphography, lymphoscintigraphy, magnetic resonance angiography, lymphedema life impact scale (LLIS) and upper limb lymphedema 27(ULL-27)questionnaires.

Results: 118 patients were evaluated. Limb circumference underestimated lymphedema compared to limb volume. Bioimpedance (L-Dex) scores highly correlated with limb volume excess (r2 = 0.714, p < 0.001). L-Dex scores were highly sensitive and had a high positive predictive value for diagnosing lymphedema in patients with a volume excess of 10% or more. ICG was highly sensitive in identifying lymphedema. Lymphoscintigraphy had an overall low sensitivity and specificity for the diagnosis of lymphedema. MRA was highly sensitive in diagnosing lymphedema and adipose hypertrophy as well as useful in identifying axillary vein obstruction and occult metastasis. Patients with minimal limb volume difference still demonstrated significantly impaired quality of life.

Conclusion: Preoperative assessment of lymphedema is complex and requires multimodal assessment. MRA, L-Dex, ICG, and PROMs are all valuable components of preoperative assessment.

Main findings

• Lymphedema evaluation included limb volume measurements ( perometry and manual circumference), bio-impedance (U400), indocyanine green lymphography bilaterally, lymphoscintigraphy, magnetic resonance angiography of the chest and upper extremities, lymphedema life impact scale (LLIS) and upper limb lymphedema 27(ULL-27)questionnaires.
• Limb volume measurements arec learly preferable to circumference measurements as the latter underestimates the degree of lymphedema.
• L-Dex was significantly correlated with ISL stage and limb volume excess] L-Dex measurements also had a high degree of sensitivity and a high positive predictive value for the diagnosis of lymphedema. L-Dex measurements were highly influenced by compression garment use.
• The L-Dex score was found to be the most rapid and reliable non-invasive method for detecting early-stage lymphedema in this study.
• There were a significant number of patients in this study with only minimal limb volume difference and early lymphedema stage who reported a high degree of impairment in quality of life. This effect was particularly striking in physical/functional and psychological domains and suggests that lymphedema symptoms are a major cause of morbidity for patients. These findings suggest that limb volume, bioimpedance, and ISL stage are inadequate in assessing the lymphedema patient, and patient reported outcome measures is an important tool for providing a more complete picture.
• MRA was found to be a very useful tool on multiple levels as it is highly sensitive in detecting lymphedema by identifying fluid in the subcutaneous tissues which is not normally present. It also directly reveals the degree of lymphedema-related fat hypertrophy which is a significant confounding variable when treating these patients. MRA revealed 15% of patients in this study had venous stenosis. This finding in our practice is further assessed with either duplex ultrasound or venography. Venous pathology is important to identify because venous hypertension may not only contribute to limb swelling but also compromise the effects of lymphovenous bypass or lymph node transplant.
• ICG lymphography appears to be the most sensitive test for lymphedema in this study. All abnormal limbs with a limb volume of >10%had abnormal ICG patterns. However, the specificity of this test has yet to be determined since this analysis would require evaluation of patients who underwent axillary lymph node dissection but did not develop clinical evidence of lymphedema.
• A limitation to this study is this patient cohort is composed of patients who, in most cases, had an established diagnosis of lymphedema. As a result, our findings cannot be compared with healthy controls or patients who had lymph node dissection and did not develop lymphedema.
• Early identification and comprehensive evaluation are key for improved outcomes using conservative therapy and surgery. Preoperative evaluation of lymphedema requires a multi-modal approach as there is not a single metric that adequately represents the state of a patient’s disease.
• Given the results in this study, all of the modalities discussed have a role:
  • MRA for evaluation of the venous system, fluid/fat composition, and evaluation of occultrecurrence;
  • ICG for screening potential candidates for LVA if they have early disease;
  • lymphoscintigraphy for evaluating preoperative and postoperative lymph node activity;
  • limb volume,
  • bioimpedance; and
  • PROMs. Prospective outcomes following surgery using these outcome measures is currently in progress and will further guide our understanding of the optimum recipe for preoperative evaluation.