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.

Study Overview

• Status: Unknown
• Conditions: Lymphedema of Upper Arm
• Intervention / Treatment: Other: Complex decongestive therapy phase 1

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Turkey
  • Istanbul, Turkey, 34899
    • Esra Giray

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Patients with post-mastectomy lymphedema; Patients with breast cancer related lymphedema

Other: Complex decongestive therapy phase 1; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subcutaneous Echogenicity Grade (SEG) medial forearm (MFA)	Medial forearm (MFA): from the medial side of the forearm to the brachioradial muscle	before treatment (T0)
Subcutaneous Echo-Free Space Grade (SEFS) medial forearm (MFA)	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	before treatment (T0)
Subcutaneous tissue thickness measurement via ultrasound over medial forearm (MFA)	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.	before treatment (T0)
Subcutaneous Echogenicity Grade (SEG) medial forearm (MFA)	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.	after treatment (T1) (through completion of four weeks of complex decongestive therapy phase 1)
Subcutaneous Echo-Free Space Grade (SEFS) medial forearm (MFA)	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	after treatment (T1) (through completion of four weeks of complex decongestive therapy phase 1)
Subcutaneous tissue thickness measurement via ultrasound over medial forearm (MFA)	Medial forearm (MFA): from the medial side of the forearm to the brachioradial muscle	after treatment (T1) (through completion of four weeks of complex decongestive therapy phase 1)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Limb volume measurement	Limb volume will be calculated based on truncated cone method from circumference measurements	before treatment (T0)
Limb volume measurement	Limb volume will be calculated based on truncated cone method from circumference measurements	after treatment (T1) (through completion of four weeks of complex decongestive therapy phase 1)
Subcutaneous Echogenicity Grade (SEG) Medial upper arm (MUA)	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.	before treatment (T0)
Subcutaneous Echo-Free Space Grade (SEFS) Medial upper arm (MUA)	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	before treatment (T0)
Subcutaneous tissue thickness measurement via ultrasound over medial upper arm (MUA)	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.	before treatment (T0)
SEG grade of medial upper arm (MUA)	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.	after treatment (T1) (through completion of four weeks of complex decongestive therapy phase 1)
Subcutaneous Echo-Free Space Grade (SEFS) Medial upper arm (MUA)	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	after treatment (T1) (through completion of four weeks of complex decongestive therapy phase 1)
Subcutaneous tissue thickness measurement via ultrasound over medial upper arm (MUA)	Medial upper arm (MUA): from the medial side of the upper arm to the biceps brachii muscle	after treatment (T1) (through completion of four weeks of complex decongestive therapy phase 1)
Subcutaneous Echogenicity Grade (SEG) Lateral upper arm (LUA)	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.	before treatment (T0)
SEFS Lateral upper arm (LUA)	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	before treatment (T0)
Subcutaneous tissue thickness measurement via ultrasound over lateral upper arm (LUA)	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.	before treatment (T0)
Subcutaneous Echogenicity Grade (SEG) Lateral upper arm (LUA)	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.	after treatment (T1) (through completion of four weeks of complex decongestive therapy phase 1)
SEFS Lateral upper arm (LUA)	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	after treatment (T1) (through completion of four weeks of complex decongestive therapy phase 1)
Subcutaneous tissue thickness measurement via ultrasound over lateral upper arm (LUA)	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.	after treatment (T1) (through completion of four weeks of complex decongestive therapy phase 1)
Subcutaneous Echogenicity Grade (SEG) Lateral forearm (LFA)	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.	before treatment (T0)
SEFS Lateral forearm (LFA)	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	before treatment (T0)
Subcutaneous tissue thickness measurement via ultrasound over lateral forearm (LFA)	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.	before treatment (T0)
SEG grade of lateral forearm (LFA)	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.	after treatment (T1) (through completion of four weeks of complex decongestive therapy phase 1)
SEFS Lateral forearm (LFA)	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	after treatment (T1) (through completion of four weeks of complex decongestive therapy phase 1)
Subcutaneous tissue thickness measurement via ultrasound over lateral forearm (LFA)	Lateral forearm (LFA): from the lateral side of the forearm to the brachioradial muscle	after treatment (T1) (through completion of four weeks of complex decongestive therapy phase 1)
Subcutaneous Echogenicity Grade (SEG) Dorsum of the hand (DH)	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.	before treatment (T0)
SEFS Dorsum of the hand (DH)	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	before treatment (T0)
Subcutaneous tissue thickness measurement via ultrasound over dorsum of the hand (DH)	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.	before treatment (T0)
SEG dorsum of the hand (DH)	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.	after treatment (T1) (through completion of four weeks of complex decongestive therapy phase 1)
SEFS Dorsum of the hand (DH)	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	after treatment (T1) (through completion of four weeks of complex decongestive therapy phase 1)
SEG grade of Dorsum of the hand (DH)	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.	after treatment (T1) (through completion of four weeks of complex decongestive therapy phase 1)
Subcutaneous Echogenicity Grade (SEG) wrist	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.	before treatment (T0)
SEFS wrist	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	before treatment (T0)
Subcutaneous tissue thickness measurement via ultrasound over wrist	Subcutaneous tissue thickness measurement via ultrasound over wrist	before treatment (T0)
Subcutaneous Echogenicity Grade (SEG) wrist	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.	after treatment (T1) (through completion of four weeks of complex decongestive therapy phase 1)
SEFS wrist	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	after treatment (T1) (through completion of four weeks of complex decongestive therapy phase 1)
Subcutaneous tissue thickness measurement via ultrasound over wrist	Subcutaneous tissue thickness measurement via ultrasound over wrist	after treatment (T1) (through completion of four weeks of complex decongestive therapy phase 1)

Collaborators and Investigators

• Sponsor: Marmara University
• Investigators: Principal Investigator: Esra Giray, Marmara University

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Anticipated): October 20, 2019
• Primary Completion (Anticipated): March 20, 2020
• Study Completion (Anticipated): March 30, 2020

Study Registration Dates

• First Submitted: October 19, 2019
• First Submitted That Met QC Criteria: October 23, 2019
• First Posted (Actual): October 25, 2019

Study Record Updates

• Last Update Posted (Actual): October 25, 2019
• Last Update Submitted That Met QC Criteria: October 23, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: ultrasound; breast cancer related lymphedema; complex decongestive therapy
• Additional Relevant MeSH Terms: Pathologic Processes; Lymphatic Diseases; Postoperative Complications; Lymphedema; Breast Cancer Lymphedema
• Other Study ID Numbers: 09.2019.866

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: The investigators don't plan to share individual participant data (IPD) in public.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No