Between November 2019 and November 2020, women with stage 2 unilateral BCRL (with at least 2 cm difference in arm circumference) who had completed active breast cancer treatment at least 12 months before were recruited for the study if they were at least 18 years old and literate as well. They were excluded in the presence of any of the followings: current recurrence of breast cancer, bilateral involvement, smoking, diabetus mellitus, pre-existing neuromusculoskeletal conditions that would affect (local) upper limb testing, edema due to other reasons (e.g. primary lymphedema, heart, kidney or liver diseases, filariasis), contraindications for CDP (e.g. deep vein thrombosis, thrombophlebitis, cardiac edema, peripheral artery disease, active infection and scleroderma), analgesic use in the last 24 hours and previous treatment for lymphedema in the last 12 months.
The study protocol was approved by the Local Ethics Committee (Date: 28.11.2019, No: KA – 19120) of our university and all subjects gave written informed consent based on the principles set out in the Helsinki Declaration.
Assessment and Outcome Measures
This study utilized a prospective study design. A socio-demographic and clinical questionnaire was used to collect information on age, height, weight, health, education, smoking habit, medications and concomitant diseases. Ultrasonographical evaluations, circumferential measurements and sensory tests were applied bilaterally before and three weeks after CDP.
A flexible tape was used to measure the circumferences at the wrist (ulnar styloid) and at each 5-cm segment until the axilla. Measurements were taken horizontally using a slight pressure. Volume was calculated bilaterally from circumference values using the truncated cone formula - which yielded excellent inter- and intra-observer reproducibility in comparison to water displacement . Lymphedema severity was determined according to the volumetric difference between the affected and unaffected limbs .
During the sensory tests, participants were seated with their forearms supinated and extended on the examination table. They were informed in details about the tests before the assessments. The patients were asked to close eyes and turn the head towards the opposite side of the testing arm. After 3-weeks of CDP treatment, at the last day of the study; the compression bandages were removed and, before the sensory measurements, patients were asked to wash their arms, lie down and rest for 30 minutes in order to reduce the effect of compression on sensory perception. As being one of the most objective sensory tests [6, 7], Semmes-Weinstein monofilaments (SWM) (North Coast Medical, Morgan Hill, CA) were used to assess tactile sensitivity of the upper extremities - volar region of the forearm, 10 cm distal to the midpoint of the medial and lateral epicondyles. The tests were started with the smallest diameter monofilament and progressed successively with larger diameter monofilaments, until the correct responses were obtained [6, 7]. Each monofilament was touched three times with 2 sec intervals and the patients were asked to say ‘yes’ when they felt the monofilament on their skin.
Static two-point discrimination test was performed with an estesiometer, in the volar region of the forearm (between the regions 8–12 cm distal to the midpoint of the medial and lateral epicondyles). The test was started with a 5 mm gap between the tips of the estesiometer. For the two-point discrimination, the tip was tapped randomly in the test area, either single or double. When the skin was touched at two points, care was taken to apply simultaneous and equal pressure. A resting time of 2 seconds was given between each application. When seven out of 10 responses of the patient were correct, the answer was considered correct. In case of incorrect answers, the test was continued until the correct answer was reached by increasing the distance between the two ends of the estesiometer by 5 mm. The lowest range value that the patient knew correctly was recorded in mm [8, 9].
Similarly, moving two-point discrimination test was also performed with an estesiometer between the regions of the upper extremity, in the volar region of the forearm 8–12 cm distal to the midpoint of the medial and lateral epicondyles. The tips of the estesiometer - placed as one or two points - were moved from proximal to distal. If seven of the 10 responses given by the patient were correct, the test was considered correct. If the answer was wrong, the gap between the tips of the estesiometer was increased by 5 mm until the right answer .
Pressure pain threshold (PPT) measurement was assessed with an algometer (J tech Algometer Commander) on both upper extremities, in the volar region of the forearm 10 cm distal to the midpoint of the medial and lateral epicondyles. With the 1 cm2 head of the algometer, pressure was applied vertically and the patient was asked to say 'yes' when he/she felt uncomfortable with the pressure. The measurement was repeated three times and PPT values were recorded by taking the arithmetic mean of three trials .
Tactile localization test was evaluated in the volar region of the forearm 8–12 cm distal to the midpoint of the medial and lateral epicondyles, using a pencil and ruler. The eyes of the patient were closed and the body surface was touched with a pencil. The patient was asked to open his eyes and show the point that was touched. The distance between the point actually touched and the point indicated by the patient was measured with a ruler in cm and recorded. A total of three measurements were done and values were recorded by taking the arithmetic mean of the three trials [12, 13].
Ultrasound (US) imaging was performed using a 5–12 MHz linear probe (Logiq P5, GE Medical Systems, Wisconsin, USA) and all the measurements were done by a single physiatrist - with more than 20 years of expertise in musculoskeletal US (LÖ). During the procedure, participants were seated with their forearms supinated and extended on a pillow. At 10 cm distal to the elbow crease, along the line parallel to the arm axis from the midpoint of the medial and lateral epicondyles, the measurements were performed bilaterally . Epidermis, dermis, and subcutaneous fat were measured by using plenty of gel and with minimum probe compression - using the automatic calculation feature of the US device.
Complex Decongestive Physiotherapy
After their initial evaluation, all patients underwent CDP phase 1 program for BCRL which comprised skin care, manual lymphatic drainage (MLD), compression bandages and exercises as recomended by the International Society of Lymphology consensus . CDP was applied by a qualified physiotherapist five times a week, for three weeks (a total of 15 sessions, 60 minutes per session). MLD was applied using the Földi method and was followed by daily multi-layered short strech bandaging worn for 23 hours a day (excluding the 1-hour treatment session). Abdominal breathing exercises and remedial exercises were performed with the bandages on. Participants were advised to avoid cutaneous effractions (e.g. insect bite, cut, burn) and to protect their skin during daily activities (e.g. using a thimble when sewing) [16, 17].
Statistical analyses were performed using the Statistical Package for the Social Sciences software, version 21.0 (IBM SPSS Statistics; IBM Corporation, Armonk, NY, USA). Normal distribution of the variables was tested by Kolmogorov-Simirnov/Shapiro-Wilk’s test. Descriptive statistics are presented with mean and standard deviation for normally distributed numerical variables. Median and interquartile width values were used for non-normally distributed numerical variables while numbers and percentages were used for categorical variables. Wilcoxon test was applied to compare the affected vs. unaffected sides and pre- vs. and post-treatment values. Mann-Whitney U test was applied to compare data pertaining to dominant vs. non-dominant upper limb involvement. Correlation analyses between skin thickness measurements (epidermis, dermis and subcutaneous fat) and sensory tests (SWM, static and moving two-point discrimination, PPT and tactile localization) were done using Spearman correlation coefficients. Statistical significance was set at p < .05. Power analysis was done using GPower program. The post-hoc power analysis (N = 27) of the Wilcoxon test for SWM values between the pre- and post-treatment results of the affected sides achieved a power of 98% with a significance level of 0.002.