Ultrasonographic Evaluation of Changes After Complex Decongestive Therapy

Evaluation of Tissue Changes Via Ultrasound After Complex Decongestive Therapy Phase I for Breast Cancer Related Lymphedema

The aim of this study is to evaluate tissue changes via ultrasound after complex decongestive therapy.

Lymphedema can be defined as the abnormal accumulation of protein-rich interstitial fluid that occurs primarily as a consequence of malformation, dysplasia, or acquired disruption of lymphatic circulation. Lymph stasis, which results in peripheral lymphedema, is characterized by edema and adipose tissue proliferation. As a vicious cycle of lymphedema progression, lymph stasis stimulates chronic inflammation because of uncontrolled responses of macrophages and CD4+ (cluster of differentiation 4) cells; fat accumulation also causes chronic inflammation by infiltration and activation of macrophages that produce inflammatory cytokines, which further promote lymph stasis directly or indirectly by decreasing lymphatic pumping and increasing capillary filtration. Lymphedema secondary to breast cancer is caused by the disruption of the lymphatic system, which in the initial stages leads to the accumulation of fluid in the interstitial tissue space and eventually is clinically presented as swelling of the arm, shoulder, neck, or torso. Complex decongestive physical therapy is a widely used nonoperative treatment of breast cancer-related lymphedema. The extremity volume has been one of the major parameters representing the treatment results of complex decongestive physical therapy. However, the increase in extremity volume in lymphedema can be caused both by tissue fluid accumulation and by pathologic tissue proliferation, which cannot be assessed separately at present. Accordingly, the volume or circumference measurement alone may not clarify how these phenomena are modified by complex decongestive physical therapy. Suehiro et al. developed subcutaneous echogenicity grade (SEG) and subcutaneous echo-free space (SEFS) grade via B-mode ultrasonography, allowing semiquantitation of nonspecific subcutaneous tissue inflammation and fluid accumulation. Increase in SEG is attributed to increased cell density and increased collagen content in the tissue and it is considered to indicate the presence of ongoing or previous inflammation in the area. SEFS represents the fluid accumulated in the spaces between superficial fasciae, which is freely mobile in the spaces. Recently, Suehiro et al. have investigated the impact of aggressive decongestion in limbs with lymphedema without SEFS in subcutaneous tissue ultrasonography. According to their results, the impact of aggressive decongestion seemed limited in patients with lymphedema without SEFS. But it was a retrospective study which may be a limitation to draw a firm conclusion. Therefore, the aim of this study is to evaluate tissue changes via ultrasound after complex decongestive therapy.

Complex decongestive therapy-phase 1 program consist of meticulous skin and nail care, manuel lymphatic drainage, compression bandages, and remedial exercises. All patients will receive manual lymphatic drainage for three times a week (Monday-Wednesday-Friday) during 4 weeks, 50 minutes a day (a total of 12 sessions) by a trained lymphatic massage therapist.

Medial forearm (MFA): from the medial side of the forearm to the brachioradial muscle SEFS grade Grade 0: No SEFS. Grade 1: Horizontally oriented (<45 degrees to the skin) SEFS only. Grade 2: Presence of vertically oriented (‡45 degrees to the skin) SEFS bridging the horizontally oriented SEFS

SEG grade of medial forearm (MFA): from the medial side of the forearm to the brachioradial muscle Grade 0: No or little increase in echogenicity in the subcutaneous layer. Horizontal or obliquely oriented echogenic lines caused by connective tissue bundles are clearly observed. Grade 1: Diffused and monotonous increases in echogenicity in the subcutaneous layer. Echogenic lines are unclear but identifiable. Grade 2: Diffused increases in echogenicity. Echogenic lines are not identifiable.

SEG grade of medial forearm (MFA): from the medial side of the forearm to the brachioradial muscle Grade 0: No or little increase in echogenicity in the subcutaneous layer. Horizontal or obliquely oriented echogenic lines caused by connective tissue bundles are clearly observed. Grade 1: Diffused and monotonous increases in echogenicity in the subcutaneous layer. Echogenic lines are unclear but identifiable. Grade 2: Diffused increases in echogenicity. Echogenic lines are not identifiable.

Medial forearm (MFA): from the medial side of the forearm to the brachioradial muscle SEFS grade Grade 0: No SEFS. Grade 1: Horizontally oriented (<45 degrees to the skin) SEFS only. Grade 2: Presence of vertically oriented (‡45 degrees to the skin) SEFS bridging the horizontally oriented SEFS

SEG grade of medial upper arm (MUA): from the medial side of the upper arm to the biceps brachii muscle Grade 0: No or little increase in echogenicity in the subcutaneous layer. Horizontal or obliquely oriented echogenic lines caused by connective tissue bundles are clearly observed. Grade 1: Diffused and monotonous increases in echogenicity in the subcutaneous layer. Echogenic lines are unclear but identifiable. Grade 2: Diffused increases in echogenicity. Echogenic lines are not identifiable.

Medial upper arm (MUA): from the medial side of the upper arm to the biceps brachii muscle SEFS grade Grade 0: No SEFS. Grade 1: Horizontally oriented (<45 degrees to the skin) SEFS only. Grade 2: Presence of vertically oriented (‡45 degrees to the skin) SEFS bridging the horizontally oriented SEFS

SEG grade of medial upper arm (MUA): from the medial side of the upper arm to the biceps brachii muscle Grade 0: No or little increase in echogenicity in the subcutaneous layer. Horizontal or obliquely oriented echogenic lines caused by connective tissue bundles are clearly observed. Grade 1: Diffused and monotonous increases in echogenicity in the subcutaneous layer. Echogenic lines are unclear but identifiable. Grade 2: Diffused increases in echogenicity. Echogenic lines are not identifiable.

SEG grade of medial upper arm (MUA): from the medial side of the upper arm to the biceps brachii muscle Grade 0: No or little increase in echogenicity in the subcutaneous layer. Horizontal or obliquely oriented echogenic lines caused by connective tissue bundles are clearly observed. Grade 1: Diffused and monotonous increases in echogenicity in the subcutaneous layer. Echogenic lines are unclear but identifiable. Grade 2: Diffused increases in echogenicity. Echogenic lines are not identifiable.

Medial upper arm (MUA): from the medial side of the upper arm to the biceps brachii muscle SEFS grade Grade 0: No SEFS. Grade 1: Horizontally oriented (<45 degrees to the skin) SEFS only. Grade 2: Presence of vertically oriented (‡45 degrees to the skin) SEFS bridging the horizontally oriented SEFS

SEG grade of lateral upper arm (LUA): from the lateral side of the upper arm to the biceps brachii muscle Grade 0: No or little increase in echogenicity in the subcutaneous layer. Horizontal or obliquely oriented echogenic lines caused by connective tissue bundles are clearly observed. Grade 1: Diffused and monotonous increases in echogenicity in the subcutaneous layer. Echogenic lines are unclear but identifiable. Grade 2: Diffused increases in echogenicity. Echogenic lines are not identifiable.

Lateral upper arm (LUA): from the lateral side of the upper arm to the biceps brachii muscle SEFS grade Grade 0: No SEFS. Grade 1: Horizontally oriented (<45 degrees to the skin) SEFS only. Grade 2: Presence of vertically oriented (‡45 degrees to the skin) SEFS bridging the horizontally oriented SEFS

SEG grade of lateral upper arm (LUA): from the lateral side of the upper arm to the biceps brachii muscle Grade 0: No or little increase in echogenicity in the subcutaneous layer. Horizontal or obliquely oriented echogenic lines caused by connective tissue bundles are clearly observed. Grade 1: Diffused and monotonous increases in echogenicity in the subcutaneous layer. Echogenic lines are unclear but identifiable. Grade 2: Diffused increases in echogenicity. Echogenic lines are not identifiable.

SEG grade of lateral upper arm (LUA): from the lateral side of the upper arm to the biceps brachii muscle Grade 0: No or little increase in echogenicity in the subcutaneous layer. Horizontal or obliquely oriented echogenic lines caused by connective tissue bundles are clearly observed. Grade 1: Diffused and monotonous increases in echogenicity in the subcutaneous layer. Echogenic lines are unclear but identifiable. Grade 2: Diffused increases in echogenicity. Echogenic lines are not identifiable.

Lateral upper arm (LUA): from the lateral side of the upper arm to the biceps brachii muscle SEFS grade Grade 0: No SEFS. Grade 1: Horizontally oriented (<45 degrees to the skin) SEFS only. Grade 2: Presence of vertically oriented (‡45 degrees to the skin) SEFS bridging the horizontally oriented SEFS

SEG grade of lateral upper arm (LUA): from the lateral side of the upper arm to the biceps brachii muscle Grade 0: No or little increase in echogenicity in the subcutaneous layer. Horizontal or obliquely oriented echogenic lines caused by connective tissue bundles are clearly observed. Grade 1: Diffused and monotonous increases in echogenicity in the subcutaneous layer. Echogenic lines are unclear but identifiable. Grade 2: Diffused increases in echogenicity. Echogenic lines are not identifiable.

SEG grade of lateral forearm (LFA): from the lateral side of the forearm to the brachioradial muscle Grade 0: No or little increase in echogenicity in the subcutaneous layer. Horizontal or obliquely oriented echogenic lines caused by connective tissue bundles are clearly observed. Grade 1: Diffused and monotonous increases in echogenicity in the subcutaneous layer. Echogenic lines are unclear but identifiable. Grade 2: Diffused increases in echogenicity. Echogenic lines are not identifiable.

Lateral forearm (LFA): from the lateral side of the forearm to the brachioradial muscle SEFS grade Grade 0: No SEFS. Grade 1: Horizontally oriented (<45 degrees to the skin) SEFS only. Grade 2: Presence of vertically oriented (‡45 degrees to the skin) SEFS bridging the horizontally oriented SEFS

SEG grade of lateral forearm (LFA): from the lateral side of the forearm to the brachioradial muscle Grade 0: No or little increase in echogenicity in the subcutaneous layer. Horizontal or obliquely oriented echogenic lines caused by connective tissue bundles are clearly observed. Grade 1: Diffused and monotonous increases in echogenicity in the subcutaneous layer. Echogenic lines are unclear but identifiable. Grade 2: Diffused increases in echogenicity. Echogenic lines are not identifiable.

SEG grade of lateral forearm (LFA): from the lateral side of the forearm to the brachioradial muscle Grade 0: No or little increase in echogenicity in the subcutaneous layer. Horizontal or obliquely oriented echogenic lines caused by connective tissue bundles are clearly observed. Grade 1: Diffused and monotonous increases in echogenicity in the subcutaneous layer. Echogenic lines are unclear but identifiable. Grade 2: Diffused increases in echogenicity. Echogenic lines are not identifiable.

Lateral forearm (LFA): from the lateral side of the forearm to the brachioradial muscle SEFS grade Grade 0: No SEFS. Grade 1: Horizontally oriented (<45 degrees to the skin) SEFS only. Grade 2: Presence of vertically oriented (‡45 degrees to the skin) SEFS bridging the horizontally oriented SEFS

SEG grade of Dorsum of the hand (DH): on the first dorsal interosseous muscle of the hand. Grade 0: No or little increase in echogenicity in the subcutaneous layer. Horizontal or obliquely oriented echogenic lines caused by connective tissue bundles are clearly observed. Grade 1: Diffused and monotonous increases in echogenicity in the subcutaneous layer. Echogenic lines are unclear but identifiable. Grade 2: Diffused increases in echogenicity. Echogenic lines are not identifiable.

Dorsum of the hand (DH): on the first dorsal interosseous muscle of the hand. SEFS grade Grade 0: No SEFS. Grade 1: Horizontally oriented (<45 degrees to the skin) SEFS only. Grade 2: Presence of vertically oriented (‡45 degrees to the skin) SEFS bridging the horizontally oriented SEFS

SEG grade of Dorsum of the hand (DH): on the first dorsal interosseous muscle of the hand. Grade 0: No or little increase in echogenicity in the subcutaneous layer. Horizontal or obliquely oriented echogenic lines caused by connective tissue bundles are clearly observed. Grade 1: Diffused and monotonous increases in echogenicity in the subcutaneous layer. Echogenic lines are unclear but identifiable. Grade 2: Diffused increases in echogenicity. Echogenic lines are not identifiable.

SEG grade of Dorsum of the hand (DH): on the first dorsal interosseous muscle of the hand. Grade 0: No or little increase in echogenicity in the subcutaneous layer. Horizontal or obliquely oriented echogenic lines caused by connective tissue bundles are clearly observed. Grade 1: Diffused and monotonous increases in echogenicity in the subcutaneous layer. Echogenic lines are unclear but identifiable. Grade 2: Diffused increases in echogenicity. Echogenic lines are not identifiable.

Dorsum of the hand (DH): on the first dorsal interosseous muscle of the hand. SEFS grade Grade 0: No SEFS. Grade 1: Horizontally oriented (<45 degrees to the skin) SEFS only. Grade 2: Presence of vertically oriented (‡45 degrees to the skin) SEFS bridging the horizontally oriented SEFS

Dorsum of the hand (DH): on the first dorsal interosseous muscle of the hand. SEG grade of Dorsum of the hand (DH): on the first dorsal interosseous muscle of the hand. Grade 0: No or little increase in echogenicity in the subcutaneous layer. Horizontal or obliquely oriented echogenic lines caused by connective tissue bundles are clearly observed. Grade 1: Diffused and monotonous increases in echogenicity in the subcutaneous layer. Echogenic lines are unclear but identifiable. Grade 2: Diffused increases in echogenicity. Echogenic lines are not identifiable.

SEG grade over wrist Grade 0: No or little increase in echogenicity in the subcutaneous layer. Horizontal or obliquely oriented echogenic lines caused by connective tissue bundles are clearly observed. Grade 1: Diffused and monotonous increases in echogenicity in the subcutaneous layer. Echogenic lines are unclear but identifiable. Grade 2: Diffused increases in echogenicity. Echogenic lines are not identifiable.

SEFS grade over wrist SEFS grade Grade 0: No SEFS. Grade 1: Horizontally oriented (<45 degrees to the skin) SEFS only. Grade 2: Presence of vertically oriented (‡45 degrees to the skin) SEFS bridging the horizontally oriented SEFS

SEG grade over wrist Grade 0: No or little increase in echogenicity in the subcutaneous layer. Horizontal or obliquely oriented echogenic lines caused by connective tissue bundles are clearly observed. Grade 1: Diffused and monotonous increases in echogenicity in the subcutaneous layer. Echogenic lines are unclear but identifiable. Grade 2: Diffused increases in echogenicity. Echogenic lines are not identifiable.

SEFS grade over wrist SEFS grade Grade 0: No SEFS. Grade 1: Horizontally oriented (<45 degrees to the skin) SEFS only. Grade 2: Presence of vertically oriented (‡45 degrees to the skin) SEFS bridging the horizontally oriented SEFS

Inclusion Criteria: -Patients with unilateral postmastectomy lymphedema with a International Society of Lymphology-ISL) stage 2 and 3 Exclusion Criteria: Bilateral lymphedema The patients who had known systemic edematogenic conditions (e.g., cardiac/hepatic/renal failure, terminal cancer, on chemotherapy), and/or with cancer recurrence Patients with contraindications for application of complex decongestive therapy (active cutaneous infection, deep vein thrombosis, cardiac edema, and peripheral artery disease)

Suehiro K, Morikage N, Yamashita O, Harada T, Samura M, Takeuchi Y, Mizoguchi T, Nakamura K, Hamano K. Skin and Subcutaneous Tissue Ultrasonography Features in Breast Cancer-Related Lymphedema. Ann Vasc Dis. 2016;9(4):312-316. doi: 10.3400/avd.oa.16-00086. Epub 2016 Nov 25.

Giray E, Yagci I. Diagnostic accuracy of interlimb differences of ultrasonographic subcutaneous tissue thickness measurements in breast cancer-related arm lymphedema. Lymphology. 2019;52(1):1-10.

Giray E, Yagci I. Interrater and Intrarater Reliability of Subcutaneous Echogenicity Grade and Subcutaneous Echo-Free Space Grade in Breast Cancer-Related Lymphedema. Lymphat Res Biol. 2019 Oct;17(5):518-524. doi: 10.1089/lrb.2018.0053. Epub 2018 Dec 20.

Sezgin Ozcan D, Dalyan M, Unsal Delialioglu S, Duzlu U, Polat CS, Koseoglu BF. Complex Decongestive Therapy Enhances Upper Limb Functions in Patients with Breast Cancer-Related Lymphedema. Lymphat Res Biol. 2018 Oct;16(5):446-452. doi: 10.1089/lrb.2017.0061. Epub 2018 Jan 22.

Suehiro K, Morikage N, Ueda K, Samura M, Takeuchi Y, Nagase T, Mizoguchi T, Hamano K. Aggressive Decongestion in Limbs with Lymphedema without Subcutaneous Echo-Free Space. Ann Vasc Surg. 2018 Nov;53:205-211. doi: 10.1016/j.avsg.2018.04.033. Epub 2018 Aug 9.