Review of Hantash BM et. al. Two articles on the Primaeva Bipolar Microneedle Radiofrequency Device

March 29, 2009

1: http://www.ncbi.nlm.nih.gov/pubmed/19226570

Lasers Surg Med. 2009 Feb;41(2):87-95.

Pilot clinical study of a novel minimally invasive bipolar microneedle radiofrequency device.

Hantash BM, Renton B, Berkowitz RL, Stridde BC, Newman J.

2: http://www.ncbi.nlm.nih.gov/pubmed/19143021

Lasers Surg Med. 2009 Jan;41(1):1-9.

Bipolar fractional radiofrequency treatment induces neoelastogenesis and neocollagenesis.

Hantash BM, Ubeid AA, Chang H, Kafi R, Renton B.

Review copyright 2009 https://aestheticdevicereview.wordpress.com

In a pair of articles published a month apart, Hantash and colleagues present the first descriptions of the histological and immunohistochemical effects of the bipolar radiofrequency needle device from Primaeva. Several of the authors are affiliated with Primaeva, and the study was funded by Primaeva. AestheticDeviceReview takes a closer look at these two papers.

Three studies were performed on human abdominoplasty or face-lift patients prior to surgery. In the first study of five patients, a broad range of dosages were applied by varying tissue temperature and duration. Histological results from this group were used to select a narrower range of dosages for examination in a 10-patient second study. Finally, in the third study, a single dosage of 72C for 4 seconds was applied to 22 patients, and both histological and immunohistochemical testing was performed.

Briefly, the radiofrequency device consists of an RF generator attached to a handpiece, which includes a single-patient-use array of 10 needles arranged in 5 pairs. The 250-micron needles are spaced 1.25mm apart, and each needle-pair is independently powered by the generator. Each needle is 6mm long, with the top 3mm insulated and the bottom 3mm exposed to allow electrical current flow. The needles are inserted at a shallow 20 degree angle to the epidermis, such that when properly placed, the tip of the needle is 2mm from the epidermis. Insertion is done by spring-loaded injection. When properly inserted, the exposed portion of the needle is positioned nearly parallel to the skin surface, at 1mm to 2mm below the surface. Each needle pair has a temperature sensor, which is used to control the power so that constant temperature can be maintained. An impedence measurement from each needle-pair also provides feedback on the depth of needle insertion. In this study, a separate skin cooling device is held against the skin after the needles are inserted, maintaining 15C to protect the epidermis from conducted heat from the RF needles. In this prototype configuration, this cooling device requires a 2nd operator, and makes the technique somewhat more difficult to apply.

Because current flows between the two needles in each pair, we expect the RF energy to create five damage zones (one between each pair), and if the heat is applied long enough, temperature conduction should expand the damage zone in all directions, resulting in one contiguous zone of damage. The surface cooling device should prevent the conducted heat from damaging the epidermis. This is exactly what the authors show. In the example shown in the paper, by setting the device at 70C for 1 sec, five zones of about 2mm by 1.25mm x 2.5mm were created. At 70C for 4 seconds, one contiguous zone of damage of about 12mm x 1.5mm x 2.75mm was created. Unfortunately, while many patients were studied, the authors did not present quantitative data on the mean and variation of the size of the damage-zones, so we are left to wonder about intra-patient variation and inter-patient variation.

This description makes it clear that the device does not provide a fractional treatment, which would be characterized by 50 or more micro-thermal-zones of damage per square centimeter. Instead this device creates one to five milli-thermal-zones of damage per square centimeter, so the term “fractional” should not be used. AestheticDeviceReview believes that the relatively large volume of RF-needle-created tissue coagulation may even turn out to offer a clinical benefit compared to fractional treatments, so the fractional label may be unwise as well as unwarranted.

Interestingly, while large amounts of tissue were coagulated, the authors show that important dermal structures such as blood vessels, hair follicles, sebaceous glands, and sweat glands were undamaged by the treatment. Men getting wrinkles treated will not have to worry about bald patches in their beards. Similarly, needles placed into the subcutaneous fat did not cause fat damage, as electrical energy appeared to flow through the interstitial collagen (fibrous septae?). AestheticDeviceReview sees some potential for this technology as a treatment for cellulite.

In the immunohistochemical study, the authors nicely show that the tissue damage is not necrosis, but a zone of thermal coagulation that proceeds through a wound healing response over several weeks, consisting of sequential phases of inflammation, proliferation and ultimately remodelling. Again this should come as no surprise, as this response is similar to that seen with several other radiofrequency devices that have been developed for shrinking collagen-rich soft tissue. For example, temperature-controlled RF needle technology is used to shrink soft palate tissue as a treatment for snoring. See company white paper at: http://www.somnus.com/abstracts/absomnus2.htm

Unlike non-ablative fractional laser treatments, all patients experienced swelling and focal edema which resolved in 48 hours following treatment. Despite the use of skin cooling, erythema appeared on the surface above each thermal damage zone, and this resolved within 8 hours of treatment. Several patients experienced purpura as well, which resolved in less than 7 days. So, overall “downtime” is greater than non-ablative fractional and less than ablative fractional laser treatments.

Is the downtime worth the result? Here, the authors leave us hanging. No data is presented on tissue shrinkage. Why didn’t the authors place tattoos prior to treatment, and measure the effect of treatment on tattoo distance? No data is presented on any change in dermal thickness. Why were so many patients studied, if quantitative histological analysis was not going to be performed? We at AestheticDeviceReview can only wait – perhaps we will see another study next month.


Review of Bousquet-Rouaud, High-frequency ultrasound evaluation of cellulite treated with the 1064 nm Nd:YAG laser

March 8, 2009

http://www.ncbi.nlm.nih.gov/pubmed/19214861

J Cosmet Laser Ther. 2009 Mar;11(1):34-44

High-frequency ultrasound evaluation of cellulite treated with the 1064 nm Nd:YAG laser.

Bousquet-Rouaud R, Bazan M, Chaintreuil J, Echague AV.

Dermatological Laser Unit, Millenium Clinic, Montpellier, France.

 

This article presents the first evaluation of the use of a high-power pulsed Nd:YAG laser for the treatment of cellulite.  Three of the four authors are employees of Candela Corporation, the maker of the laser.

The study at first appears to be well-designed.  Quantitative endpoints of dermis thickness and ultrasound density were chosen, and preliminary studies were performed to show that measurement methods were not subject to intra-observer or inter-observer error.  Twelve patients were treated, with one thigh randomized to treatment and the other randomized to control.  In addition to pre-treatment ultrasound measurements, follow-up measurements were performed at 1 month and 3 months after the final treatment of the series of three treatments.  Adjunctive photographs were taken before each treatment, and presumably at the follow-up visits.  The example photograph appears to be of high quality.  The treatments were appropriately standardized to minimize the impact of dosage variation on outcome.  Likewise, the patient population appears to be reasonably homogenous in terms of age, body mass index, and pre-treatment evaluation of cellulite severity, to minimize the impact of patient variation on outcome variation.

Given the apparent care taken in the study design, the analysis was extremely disappointing.  The analysis presents only the variation in ultrasound measurements of the treated thigh, and completely ignores the control thigh.  The authors claim that the mean dermal thickness of treated thighs decreases from the beginning to the end of the study, but this is a flawed claim.  Because they do not present data on the control thigh, we cannot know if this result stems from a treatment effect, or from a natural variation in the patient population over time.  For all we know, the dermal thickness of the control thigh improved more than the treated leg.  This is the whole point of having a control thigh.  No other control variables, such as BMI or weight, were presented.

Further, the authors include the raw data for the dermal thickness measurements in all 12 patients, but offer no explanation why some patients have increased thickness at 1 month follow-up which then decreases at 3 months, while other patients show decreased thickness at 1 month with subsequent increases at 3 months.  Presumably, the treatment effect would go in generally the same direction in this homogeneous group that recieved the same treatment regime.  This variation adds to the concern that something else was going on with these patients during the study that might effect dermal thickness.  The same comments apply to the raw data on dermal echogenicity.

The exclusion of measurements of the control thigh from the analysis renders any conclusions moot.  The authors further present patient satisfaction data.  This type of data is notoriously challenging to interpret, as patients often feel satisfied that they are taking steps towards treating a condition. In this case, on average the patients reported being somewhat satisfied, and no patients reported being very satisfied.  Readers of the article should not be satisfied at all.


Review of Lach E, Reduction of subcutaneous fat and improvement in cellulite appearance by dual-wavelength, low-level laser energy combined with vacuum and massage

February 15, 2009

http://www.ncbi.nlm.nih.gov/pubmed/19093288

 

J Cosmet Laser Ther. 2008 Dec;10(4):202-9.

 

Reduction of subcutaneous fat and improvement in cellulite appearance by dual-wavelength, low-level laser energy combined with vacuum and massage.

 

Lach E.

 

Boston Surgical Group, Southborough, MA 01772, USA.

 

 

In this article, Elliot Lach MD presents the first publication of the clinical results achieved with the new SmoothShapes cellulite treatment device.  Note that Lach is the inventor of the technology and a shareholder in Eleme, the company which makes the device.

 

In this study of 102 female patients, one thigh was randomized to treatment with the SmoothShapes device and one thigh to massage-alone.  Patients received an average of 14.3 treatments over 4 to 6 weeks.  MRI measurements, thigh circumference measurements and photographs were taken of each patient.  A patient satisfaction questionnaire was completed at the end of the study.  In SmoothShapes treated legs, MRI showed an average decrease in fat thickness of 1.19cm2 from a baseline average of 136.57cm2, which is less than 1% change.  In the control legs, MRI showed an average increase in fat thickness of 3.82cm2 from a baseline average of 133.98 cm2, about a 2% change.  The thigh circumference measurements showed no significant difference between the two SmoothShapes treatment and the control.  While photographs were taken, no grading of the photographs for severity of cellulite was presented.

 

While the MRI results are statistically significant, a <1% decrease in fat thickness cannot be considered clinically significant.  The increased fat thickness in the massage-only group remains unexplained.  No covariance analysis of weight gain or reduction was provided.  While the title of the article refers to “improvement in cellulite,” no evidence of any improvement in the appearance of cellulite was presented.  While patient satisfaction was reported at 72.6%, a placebo effect cannot be ruled out.  Alternatively, a quantifiable evaluation of cellulite appearance should have been easy to perform, by asking the blinded patient and/or a blinded observer to identify the leg that was treated versus the leg receiving massage only (50% correct responses would result from chance, while 100% correct responses would indicate meaningful improvement in all cases).

 

In summary, this study failed to show clinically significant reductions in subcutaneous fat or body circumference, nor was improvement in cellulite appearance shown.  One is left to wonder whether the device has any effect at all.