Lasers in Surgery and Medicine 46:20–26 (2014)

Enhanced Clinical Outcome with Manual Massage

Following Cryolipolysis Treatment: A 4-Month
Study of Safety and Efficacy
Gerald E. Boey, MD
and Jennifer L. Wasilenchuk
Arbutus Laser Centre, Vancouver, British Columbia, Canada

Background and Objectives: Cryolipolysis procedures While the mechanisms of fat reduction are not entirely
have been shown to safely and effectively reduce the understood, studies have shown that cold exposure induces
thickness of fat in a treated region. This study was apoptotic cell death of subcutaneous fat cells [4–5].
conducted to determine whether the addition of post- Cryolipolysis is approved by the FDA, Health Canada
treatment manual massage would improve efficacy while and the European Union as a non-invasive treatment for
maintaining the safety profile of the original cryolipolysis the reduction of localized subcutaneous fat [6]. Recent
treatment protocol. studies have focused on improving and optimizing cry-
Materials and Methods: The study population consisted olipolysis treatment protocols to enhance the reduction of
of an efficacy group (n ¼ 10) and a safety group (n ¼ 7). fat. Two studies suggest that a second successive course of
Study subjects were treated on each side of the lower treatment may improve the efficacy of this procedure [6].
abdomen with a Cooling Intensity Factor of 42 (72.9 mW/ One study demonstrated, however, that a second treat-
cm2) for 60 minutes. One side of the abdomen was ment improved efficacy in the abdomen area but not the
massaged post-treatment and the other side served as love handles [7]. Because cryolipolysis is still a relatively
the control. Immediately post-treatment, the massage side new procedure, treatment protocols have yet to be refined
was treated for 1 minute using a vigorous kneading motion and optimized to maximize results.
followed by 1 minute of circular massage using the pads of The purpose of this study is to evaluate whether the
the fingers. For the efficacy group, photos and ultrasound addition of a post-treatment manual massage enhances
measurements were taken at baseline, 2 months, and the effectiveness of a single cryolipolysis treatment.
4 months post-treatment. For the safety group, histological Additionally, this study evaluates the safety of incorpo-
analysis was completed at 0, 3, 8, 14, 30, 60, and 120 days rating post-treatment manual massage into cryolipolysis
post-treatment to examine the effects of massage on treatment.
subcutaneous tissue over time.
Results: Post-treatment manual massage resulted in a METHODS
consistent and discernible increase in efficacy over the non- All studies were conducted using a commercially
massaged side. At 2 months post-treatment, mean fat layer available non-invasive medical device for cryolipolysis
reduction was 68% greater in the massage side than in the (CoolSculpting, ZELTIQ Aesthetics, Pleasanton, CA).
non-massage side as measured by ultrasound. By 4 months, Subjects were selected from new patient consultations or
mean fat layer reduction was 44% greater in the massage referrals from friends and family. Study subjects received
side. Histological results showed no evidence of necrosis or treatments free of charge but were not otherwise
fibrosis resulting from the massage.
Conclusion: Post-treatment manual massage is a safe
and effective technique to enhance the clinical outcome
from a cryolipolysis procedure. Lasers Surg. Med. 46:20– This is an open access article under the terms of the Creative
Commons Attribution-NonCommercial-NoDerivs License, which
26, 2014. ß 2013 The Authors. Lasers in Surgery and permits use and distribution in any medium, provided the
Medicine Published by Wiley Periodicals, Inc. original work is properly cited, the use is non-commercial and
no modifications or adaptations are made.
Conflict of Interest Disclosures: All authors have completed
Key words: body contouring; cryolipolysis; non-surgical and submitted the ICMJE Form for Disclosure of Potential
fat reduction; post-treatment massage Conflicts of Interest and have disclosed the following: [Dr. Boey is
a consultant to ZELTIQ. Ms. Wasilenchuk has no relevant
conflicts of interest to disclose].
INTRODUCTION Contract grant sponsor: ZELTIQ Aesthetics, Pleasanton, CA.


Cryolipolysis is a novel non-invasive fat reduction Correspondence to: Gerald Boey, MD, Arbutus Laser Centre,
2025 W. Broadway Suite 106, Vancouver, BC, Canada V6J 1Z6.
technique that applies controlled localized cooling to the E-mail: [email protected]
skin surface to reduce subcutaneous fat. Cryolipolysis Accepted 18 November 2013
Published online 11 December 2013 in Wiley Online Library
procedures can safely and effectively reduce fat without (wileyonlinelibrary.com).
damaging overlying skin or surrounding structures [1–3]. DOI 10.1002/lsm.22209

ß 2013 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.
 ENHANCED CLINICAL OUTCOME WITH MANUAL MASSAGE 21

compensated. Prior to treatment, trained clinicians col- consistent thermal coupling between the skin and the
lected patient data including gender, weight, age, height, applicator, a pad saturated with a coupling gel (ZELTIQ
BMI, and medical history. Aesthetics) was placed on the skin surface prior to placing
Subjects were screened based upon the following the applicator on the abdomen. A medium applicator
inclusion/exclusion criteria. Subjects included in the study (CoolCore applicator) was applied with moderate vacuum
had a visible bulge of adipose tissue on their abdomen pressure to gently draw a bulge of fat into the applicator
below the umbilicus and stated willingness to maintain cup. Treatment was delivered at a Cooling Intensity Factor
weight within 10 lbs for the duration of the study. No 42, corresponding to an average energy extraction rate of
adjunctive fat reduction therapies were used over the 72.9 mW/cm2.
course of the study. Subjects were excluded if they had Immediately following treatment, one side of the
undergone liposuction, other surgical procedures, or abdomen was manually massaged for 2 minutes (Fig. 2).
abdomen contouring treatments in the past 6 months. The side of the abdomen that received the massage was
They were excluded for history of cryoglobulinemia, randomly assigned. The first minute of massage consisted
paroxysmal cold hemoglobinuria, cold urticaria, areas of of a vigorous kneading motion, during which the tissue was
impaired peripheral circulation, Raynaud’s disease, preg- pulled together between the thumb and fingers and then
nancy, scar tissue, or extensive skin conditions, such as pulled away from the body. The second minute of massage
eczema or dermatitis at the treatment area, impaired skin consisted of circular massage, during which tissue was
sensation, open or infected wounds, and area of recent pushed down into the body and then moved in a circular
bleeding or hemorrhage. Also, subjects with skin laxity or motion.
enrolled for other clinical studies were excluded.
Efficacy was determined using photographic and ultra- Method of Evaluating Efficacy
sound analysis at 2 and 4 months post-treatment. Safety The efficacy of adding a 2-minute manual massage
was evaluated from a separate group of 7 subjects by following cryolipolysis was evaluated using pre- and post-
assessing side effects and analyzing histology. Subjects treatment photographs and ultrasound measurement of
received cryolipolysis treatments prior to abdominoplasty fat layer reduction in the massaged and non-massaged
surgery and the resected tissue underwent histology sides. Both photographic and ultrasound images were
processing, imaging, and analysis. taken at baseline, 2 months, and 4 months post-treatment.
Fat layer reduction, as demonstrated by fat layer
Treatment Method thickness changes measured by ultrasound, was confirmed
As illustrated in Figure 1, the cryolipolysis vacuum by comparing pre-treatment and post-treatment images,
applicator was used to sequentially treat the left and right in which each ultrasound image pair corresponded to the
sides of the abdomen below the umbilicus for 60 minutes same anatomic area. An ultrasound system (SonoSite
each. Immediately following cryolipolysis treatment, one TITAN, Bothell, WA) with a 7.5-MHz high-resolution
side of the abdomen was manually massaged using a 2- linear transducer was used to acquire images of the fat
minute protocol, while the remaining side served as a layer. A series of evenly spaced pre-treatment images were
control. acquired, as shown in Figure 3, with five images captured
Cryolipolysis was administered to abdominal tissue through the untreated control area in the upper abdomen
drawn between cooled plates in the applicator. To ensure and 10 through the treatment area in the lower abdomen.

Fig. 1. Cryolipolysis treatments were delivered using a vacuum Fig. 2. Immediately following cryolipolysis treatment, the tissue
applicator to the left and right sides of the lower abdomen. One was vigorously kneaded and pulled away from the body for
side was manually massaged immediately post-treatment, while 1 minute then pushed into the body in a circular massage motion
the other side was the non-massage control. for 1 minute.
22 BOEY AND WASILENCHUK

evaluation of tissue histology. Patients were assessed

immediately following treatment (0 day) and 3, 8, 14, 30,
60, and 120 days post-treatment to evaluate damage to the
dermis or epidermis in the areas treated. Histology has been
used to assess cold-induced panniculitis at the dermal-fat
interface following cryolipolysis treatment and to evaluate
the time course of inflammatory activity [2,3]. In this study,
the histology was also evaluated for additional tissue injury
induced by the post-treatment manual massage.

RESULTS
A total of 10 subjects were assessed for efficacy by
baseline ultrasound and photography and seven subjects
were evaluated for safety by histology. The analyzed
Fig. 3. Ultrasound images were acquired of the cryolipolysis patient population was entirely female with age range 30–
treated lower abdomen and the untreated control upper abdomen. 50 years, weight range 129–147 lbs, BMI range 21–25, and
Ten images were taken of the lower abdomen (five from the height 50 200 to 50 800 . All patients maintained body weight
massaged side, five from the non-massaged side) and five images
were taken from the control area. within the specified 10 lbs over the course of the study,
ranging from a 6 lb loss to an 8 lb gain. Of the original 10
Overall fat layer thickness changes were normalized by subjects treated for efficacy assessment, one was lost at
subtracting the control site difference from the treated site 2 months follow-up and an additional subject was lost at
difference. For each subject, multiple fat layer reduction 4 months follow-up; both subjects were lost due to
measurements were obtained and averaged to determine a inconvenience of follow-up rather than procedure-related
mean fat layer thickness change. adverse event or treatment failure.

Method of Evaluating Safety Efficacy Results

The safety of adding a 2-minute manual massage For all subjects treated, the cryolipolysis procedure
immediately following cryolipolysis was assessed on a group visibly reduced the size of the lower abdomen, as
of seven patients by monitoring procedural side effects and demonstrated by ultrasound measurements and

Fig. 4. Subject #8 had post-treatment massage on left and non-massage control on right.
Photographic analysis of post-treatment manual massage at baseline (a), 2-months (b), and 4-
months (c) post-treatment.
 ENHANCED CLINICAL OUTCOME WITH MANUAL MASSAGE 23

Fig. 5. Subject #10 had post-treatment massage on left and non-massage control on right.
Photographic analysis of post-treatment manual massage at baseline (a), 2-months (b), and 4-
months (c) post-treatment.

Fig. 6. Subject #6 had post-treatment massage on left and non-massage control on right.
Photographic analysis of post-treatment manual massage at baseline (a), 2-months (b), and 4-
months (c) post-treatment.
24 BOEY AND WASILENCHUK

Fig. 7. Subject #2 had post-treatment massage on left and non-massage control on right.
Photographic analysis of post-treatment manual massage at baseline (a), 2-months (b), and 4-
months (c) post-treatment.

photography. Figures 4–7 show photos taken at baseline, standard deviation 1.9 mm, range 1.1 to 5.0 mm) for the
2 months, and 4 months post-treatment. non-massaged side and 21.0% with standard deviation
Ultrasound measurements of fat reduction between 8.5% and range 10.0 to 34.9% (mean 4.2 mm, standard
massaged and non-massaged sites 2 months post-treat- deviation 2.2 mm, range 0.8 to 7.2 mm) for the massaged
ment are shown in Figure 8. In all patients at 2 months, side. Thus, mean fat reduction was 68% greater on the
there was a significant decrease in fat layer thickness on massaged side at 2 months. At 4 months post-treatment,
the side that was massaged post-treatment. The normal- the normalized mean fat layer reduction was 10.3% with
ized mean fat layer reduction was 12.6% with standard standard deviation 8.6% and range 2.6 to 25.8% (mean
deviation 7.2% and range 2.4 to 20.0% (mean 2.6 mm, 1.9 mm, standard deviation 1.1 mm, range 0.5 to 3.9 mm)

Fig. 8. Fat layer reduction for nine subjects at 2 months. Mean fat Fig. 9. Fat layer reduction for eight subjects at 4 months. Mean
layer reduction was 68% greater for the massaged compared to the fat layer reduction was 44% greater for the massaged compared to
non-massaged side following cryolipolysis. the non-massaged side following cryolipolysis.
 ENHANCED CLINICAL OUTCOME WITH MANUAL MASSAGE 25

Fig. 10. Histology images of abdominal tissue manually massaged post-treatment showed no
evidence of necrosis or fibrosis. The massaged and non-massaged tissue looked similar. H&E stain,
40 magnification.

for the non-massaged side and 14.9% with standard post-treatment massage with P ¼ 0.0007 at 2 months, but
deviation 6.1% and range 5.3 to 22.1% (mean 2.7 mm, P ¼ 0.1 at 4 months. It may be indicative that manual
standard deviation 1.5 mm, range 0.4 to 4.9 mm) for the massage caused an additional mechanism of damage
massaged side. At 4 months, the mean fat layer reduction immediately following treatment, perhaps from tissue
was 44% greater in the massaged side, Figure 9. reperfusion injury. With additional time, however, the
cold-induced apoptosis is likely to cause gradual, ongoing
Safety Results fat cell destruction in both the massaged and non-massaged
Treatment sites were evaluated immediately following treatment areas. The mechanism of action by which
post-treatment manual massage for any epidermal, der- cryolipolysis induces damage to adipocytes is not well
mal, or subcutaneous findings. Non-massage sites were understood and remains an ongoing subject of research.
assessed immediately following cryolipolysis. In all cases, The ultrasound fat layer measurements in this study yielded
typical side effects, such as erythema, bruising, minor pain, results that were lower than the typical published results of
and transient loss of sensation, were observed. Aside from approximately 20%. This is likely due to the small sample
one subject that reported slight numbness in the massaged size since there is a significant range in patient response to
side for 8 weeks, typical side effects resolved spontaneously non-surgical fat reduction procedures, such as cryolipolysis.
within 14–30 days and no adverse events were reported. The manual massage sensation was reported to be
Safety was evaluated by histological analysis at 0, 3, 8, uncomfortable but not painful, and it is likely that the level
14, 30, 60, and 120-day time points post-treatment. As of discomfort is acceptable to the patient given the
shown in Figure 10, the post-treatment massage tissue resultant increased treatment efficacy. No long-term side
showed no evidence of necrosis or fibrosis at any of the time effects or adverse events were reported. Therefore,
points. The non-massage tissue also did not show cryolipolysis is shown to be a well-tolerated, efficacious
abnormality following cryolipolysis treatment at 0, 3, 8, treatment method for decreasing fat layer thickness in the
14, 30, 60, and 120 days post-treatment. The histological lower abdomen. As cryolipolysis treatment protocols
timeline shows increasing inflammatory response, peak- continue to be refined and optimized, post-treatment
ing at 30 days with dense inflammatory cell infiltrate and manual massage is one technique that can be incorporated
reduction in adipocyte size, then decreasing to a similar to safely improve treatment efficacy.
response at 60 and 120 days, with reduced adipocyte size
and decreased infiltrates.
CONCLUSION
DISCUSSION This study found that post-treatment manual massage
Incorporating manual massage immediately following improved cryolipolysis treatment efficacy. At 2 months
cryolipolysis treatment appears to significantly increase follow-up, the massaged sites had mean fat layer reduction
treatment efficacy. While the 2-month follow-up data showed 68% greater than the non-massaged sites. By 4 months
68% increase in fat layer reduction in the massaged post-treatment, the massaged sites had 44% greater fat
compared to the non-massaged treatment area, the 4-month layer reduction compared to the non-massaged treatment
measurements showed a 44% increase in fat layer reduction. sites. Histological analysis of massage tissue at 0, 3, 8, 14,
Although it is still an improvement in fat layer reduction, it is 30, 60, and 120 post-treatment found no evidence of fibrosis
unknown why the effect was more pronounced at the 2- or necrosis. The massaged and non-massaged tissues
month timepoint. A paired t-test found significant effect from looked similar. Thus, post-treatment manual massage is
26 BOEY AND WASILENCHUK

shown to be a safe and effective method to further reduce non-invasive fat removal. Lasers Surg Med 2008;40(9):
the fat layer following a cryolipolysis procedure. 595–604.
3. Zelickson B, Egbert BM, Preciado J, Allison J, Springer K,
Rhoades RW, Manstein D. Cryolipolysis for noninvasive fat
ACKNOWLEDGMENTS cell destruction: Initial results from a pig model. Dermatol
The authors acknowledge Kevin Springer and Bill Surg 2009;35(10):1462–1470.
4. Preciado J, Allison J. The effect of cold exposure on adipocytes:
Blaker for assistance with ultrasound imaging and clinical Examining a novel method for the noninvasive removal of fat.
photography. Cryobiology 2008;57(3):327.
5. Nelson AA, Wasserman D, Avram MM. Cryolipolysis for
reduction of excess adipose tissue. Semin Cutan Med Surg
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