Abstract
Cryolipolysis is a non-invasive treatment for fat located in panniculitis due to cold. The objective of this research was to determine the effectiveness and safety of contrast cryolipolysis in the subcutaneous the reduction of fat. Contrast cryolipolysis is a combination of the principles in traditional cryolipolysis with the addition of periods of heating which are consistent with the process of contrast lipocryolysis.
Twenty-one subjects between 34 and 9 were treated with cryolipolysis using contrast in the area of the abdomen and flanks using Polarys(r) Polarys(r) device. Anthropometry and standardized photographs as well as measurements with ultrasounds and a skinfold caliper to determine the cause were performed at baseline and also after the follow-ups of 30-60 and 90 days after treatment. The safety tests included laboratory testing and monitoring for adverse events. The significance threshold for the tests was set to P less that 0.05. Weight of patients was not significantly different , nor body mass index was measured.
Measurements of waist taken at the baseline as well as the 30-day follow-up demonstrated significant differences as was the case of measurements taken at the 30 and 60-day follow-ups. The skinfold and ultrasound measurements showed significant decreases in the areas treated at every time point when contrasted with the baseline. The results from the laboratory did not show any significant differences in comparison to the baseline. In the case of acute adverse reactions, they were treated quickly. The research proved that cryolipolysis with contrast is safe and effective in reducing fat and improving the shape and contouring of your body.
- Introduction
Localized adiposity can be described as an unusual accumulation of fat at normal anatomical areas, and it is an extremely unaesthetic issue. The practice of liposuction has been as the best treatment option for body contouring, however, due to the risk of complications that could arise from the procedure, new methods were devised. Several treatments, including radiofrequency, ultrasound, and mesotherapy, have been developed to achieve adipocyte destruction. Each treatment employs a unique mechanism that triggers necrosis or apoptosis in the adipocytes targeted.
In recent years, a new technology for the noninvasive treatment of localized fat through cold-induced panniculitis called cryolipolysis, appeared. The method relies on the notion that tissues with lipids are more prone to injury by cold than tissues that are water-rich. However, studies have shown that 13 have demonstrated that, by alternating low temperatures and heating cycles and cooling, the lipids inside the adipocytes are more likely to crystallize and quickly, similar to the tempering process used in the food industry.
This could improve the outcomes when treating. This is known as contrast lipocryolysis. In light of these two concepts (cryolipolysis in contrast with the variant of lipocryolysis) an ingenious method was developed called cryolipolysis in contrast. This method is different from the traditional cryolipolysis method by using cooling and heating time and also is different from contrast lipocryolysis, by using cooler temperatures to facilitate the cooling method.
A contrast of cryolipolysis that is conventional and cryolipolysis with contrast.
Although numerous studies that have been published on cryolipolysis that are conventional, accessible studies, that study the results of cryolipolysis in contrast are very rare. This is why the goal in this research was to determine the effectiveness and safety of this method.
2. Materials and Methods
2.1. Subjects
This study was carried out with 21 healthy subjects aged between 18 to 50 years old. The criteria to be included in the study included an absence of fat subcutaneous in the abdomen and flanks as well as an index of body mass (BMI) lower then thirty. The participants were not included if they underwent cosmetic procedures, suffered from abdominal region within 6 months preceding the start in the research, expecting or experienced an unplanned pregnancy (within the last six months) or had a history of cryoglobulinemia or cold urticaria as well as chronic bleeding hemoglobinuria.
The decision of which part will be addressed (i.e. the abdomen or flanks) was determined by the specific needs of the patient.
Points of evaluation and also designated areas to be treated. Every subject was treated at one or more locations for five treatment zones. The areas were treated with either the large or medium applicator depending on the area of of fat localized.
The examination of body composition performed at baseline , and then after the follow-ups of 30-60 and 90-days following this treatment.
2.2. Ethical Aspects
The Research Ethics Committee: Institutions, Teaching, and Research approved this study.
All participants have signed informed consent forms and the procedure was carried out by a physiotherapist who was trained in the Clinical Laboratory of the Ibramed Center for Education and Advanced Training.).
2.3. Sample Size
The sample size was calculated by using an increase of 2.0 millimeters inside the adipose layer , which was determined using an ultrasound. Standard deviations from 2.0 millimeters also was considered as a result of the previous study 25 on the effect of cryolipolysis on abdominal fat for women. The significance of 0.05 and an 80% power. The Minitab software identified that 17 patients needed (Minitab, v.17, StateCollege, PA). Therefore in order to ensure that there was no loss of samples which might hinder analysis of data 21 patients were chosen.
2.4. Treatment Protocol
Subcutaneous fat which is located in abdomen and flanks was treated with cryolipolysis using contrast. It was heated to temperatures of 40 degrees Celsius over 10 minutes, then it was chilled down to about 60 mins (-8degC) The temperature was raised again to 40degC over 10 minutes by using the cryolipolysis machine Polarys(r) (Ibramed Brazilian Industria do Equipamentos Médicamentos of EIRELI).
Patients were treated at the same location or in multiple locations in order to treat as many as five zones in one treatment or 2 sessions. The zones were treated with either the medium or large applicator according to the area of the fat region and the anatomical limitations of the applicator’s location. The treatment sessions were carried out with the patient sitting comfortably in the dorsal decubitus posture , with an angle of 45 degrees when using stretchers or when in the more lateral position. The applicator that was curved for the vacuum was positioned at the center of the area to be treated and the vacuum was activated. This vacuum was able to anchor the applicator in the area of treatment, and the cushions held it in place throughout the entire process.
2.5. Anthropometric Measurements
The participants all took an anthropometric measure at baseline and during intervals of follow-ups for 30-60 or 90 days following treatment. To determine their height and weight , the participants were only wearing their underwear with no shoes. A stadiometer from the traditional machine (model 110 CH Welmy, Sao Paulo, Brazil) was employed. The circumference of the abdomen was measured using the help of a measuring tape that was elastic. Every measurement was taken from the center of the measurement to ensure that future measurements were taken from the same location.
2.6. Questionnaire
Patients were asked to complete a questionnaire that assessed the degree of tolerance to this treatment. Patients were asked to rate their tolerance to the treatment by selecting 1 for those who are intolerant, 2 for discomfort, 3 for inacceptable and 4 for being extremely comfortable.
2.7. Skinfold Caliper
Skinfold calibration was used to determine the region that has the highest thickness within the treatment area for patients who are able for measurements at the beginning of the treatment , and after 30-60 and 90 days after the procedure.
2.8. Ultrasound Analysis
The subjects underwent an ultrasound to determine the cause of the problem prior to the beginning of the treatment as well as after the follow-up visits of 30 days, 60 and 90 days after the treatment. The evaluation of ultrasound was performed using the linear transducer which had an amplitude ranging from 6 to 18 Mhz (MyLab(tm)25 Gold Esaote Italy). The images were analyzed by the quantitative measurement of subcutaneous tissues that lie between two anatomic planes: the dermis and the muscle fascia. It is the amount of fat present in the treatment area is measured in millimetres. One physiotherapist was who was educated to master the process of taking measures. The probe was placed on previously defined locations of the area of treatment coupled gel , as well as without compressing it.
2.9. Standardized Photographs
Digital images of standard quality were taken with the help of the digital camera (Canon EOS Rebel T3i, Canon USA Inc., Melville, NY, USA) at the start of the study as well as at an interval of 90 days after treatment. The subjects were photographed in seated positions with three perspectives, including the back view as well as the left and right perspective. Each photograph was taken at 1 millimeter distance.
2.10. Safety Assessments
The safety tests consisted of tests in the laboratory as well as monitoring for adverse incidents. These blood samples were collected during the initial time, and 14-21 days after treatment for the purpose of examining fasting glucose levels and the lipid profile and also the liver’s performance. All blood samples from patients were taken via venipuncture in the early morning after an overnight fast lasting between 12 to 14 hours.
Following the blood samples were collected, they were examined and processed in a laboratory named The Sao Francisco Laboratorio of Analises Clinicas (Amparo, SP, Brazil). Serum lipids were measured for the components cholesterol, triglycerides, and very low-density cholesterol from lipoproteins (LDL) as well as high-density lipoprotein and low-density cholesterol. Tests of blood that are relevant to liver function were determined by studying the indicators of liver function: aspartate aminotransferase as well as Alanine aminotransferas. Subjects who had baseline laboratory results which were not within the normal range of reference were not included in the analysis. The frequency of adverse reactions was noted throughout the the study.
2.11. Statistical Analysis
The statistical analysis was conducted with Graph Pad Prism 6 (La Jolla, CA, USA). The hypothesis of normal distribution was verified using an Shapiro Wilk test. The difference between the baseline and posttreatment values were analyzed using ANOVA, as well as Tukey’s multi-comparatives test or Friedman test, and Dunn’s Multi-Comparatives Test. To examine the relationship between blood-liver test results for glucose as well as serum-liver and serum-lipid levels at baseline and 3 weeks after the treatment were assessed using the test of pair and tests such as the Wilcoxon signs-rank test. The significance threshold on each of the tests was set at 0.05 ( more that 0.05).
3. Results
Twenty-one patients were enrolled and completed treatment (18 females , and three men). The subjects ranged between the ages of 21 to 50, with a mean and an average deviation of 34+9 months. Their weights among the patients varied from 57.5 and 90.5 kg, with the median and the standard deviation 70.3 +9. Their BMI ranged from 21.8 between 21.8 and 30.0 with a median and a standard deviation of 25.7 +2. Weight and BMI didn’t change significantly following the treatment. This waist-circumference is presented in Figure 3.. The measurements from the baseline follow-up , and 30 days later, showed statistically significant differences that were similar to those observed in the 30-day and 60-day follow-ups. There were not any significant differences between measures of the follow-up of 30 days, or from the baseline.
Means using an error normal of the waist circumference before treatment (baseline) and post-treatment (30 30, 60 , and 90 days after treatments).
P< 0.05).
The patients were able to endure the treatment. 35 per cent (N from 8) of the participants said the treatment was satisfactory, and 60% (N more than 12) said that they found the treatment satisfied. One participant (5 percent) believed that the treatment was unpleasant.
The results from the skinfold caliper were analyzed to assess the efficacy of the treatment. The decrease in the thickness of the skinfolds of the follow-ups as well as the baseline values for the regions which were treated proved to be the highest in significance in statistical terms ( P < 0.05)
Means of the average of the standard deviation of abdominal of the skinfold prior to treatment (baseline) and post-treatment (30 30, 70 or 90 days after treatment ).
P < 0.05.
Ultrasound images were analyzed to determine the amount of reduction in the fat layers.
Note the hyperechoic zones: bright echos and high-reflective structures (white refers to dermis fascia and the fibrotic septa)–and hypoechoic zones that have small reflections, echoes and intermediate transmission (gray is adipose tissue and muscles in the skeletal). The boxes show the areas to be assessed, as is the diminution of the thickness of the abdomen following treatment.
The reductions in the fat layer were highly significant across both of the areas that include the abdomen, as well as the flanks. The median amount of reduction in the fat layer of 21.6 percentage in abdominal. Reduced amounts of more than 50.1 percent were seen between the beginning of treatment and 90 days following procedures. for the flanks). the mean diminution was 14.5 percent. However, reductions up to 43.2 percent were observed at the time of the first treatment and the 90-day period following the treatment.
Means of an average deviation of that of abdominal fat thickness assessment by diagnostic ultrasound prior to beginning the treatment (baseline) and after treatments (30 60-70 and 90-days after treatment) and flank fat thickness assessment by diagnostic ultrasound prior treatment (baseline) and after treatment (30 60 30 and 90 days after treatments).
P < 0.05.
7. The abdominal and flank areas significantly decreased between the initial and 90-day post-treatment.
Comparison between baseline and 90-day post-treatment follow-up using cryolipolysis.
The laboratory’s results are presented in the table. The average value and standards deviations of the liver-related tests that test fasting glucose and serum lipids from the baseline were analyzed and compared to the results three weeks later after having the procedure. There were no significant changes.
Mean (SD) when it comes to the situation of fasting glucose levels along with blood tests for liver function and serum levels of lipids.
4. Discussion
The objective of this research was to determine the efficacy in the safest and most effective way to use cryolipolysis using contrast, a method that blends the fundamentals of cryolipolysis which are standard and the procedure of contrast lipocryolysis which involves heating for a certain amount of duration.
The mechanism that causes cryolipolysis can cause damage to adipocytes isn’t yet understood, and is an area of ongoing research. The effectiveness and safety of this procedure are generally accepted, however it is important to note that the majority of the studies published employ an instrument that uses an intensity factor for cooling (CIF) which doesn’t display temperature in Celsius.
The initial study in which 29 animals using a conventional cryolipolysis model to examine the effects on the skin’s the surface of controlled cold on the skin’s surface and the subsequent specific destruction of the subcutaneous fat the use of a folded-cooled metallic sheet. The skin’s surface were exposed to cooling at different temperatures (20degC 1, 1degC and -3degC and -5degC, and 7 degrees Celsius) which was 20degC, considered to be the standard temperature. The process took about 10 minutes. Researchers observed that the loss of fat cells occurred when the cooling panels had been cooled to 1 degree Celsius.
However, when contrasted with the control tests, the most powerful results were observed at the temperature of 7degC. In the follow-up study 30], conducted using pigs, researchers converted the temperature to degrees Celsius to milliwatts/square centimeter. They transformed the result to CIF, which refers to a number used to describe the method of removing heat (cooling). Researchers discovered an inflammatory response that was gradual following treatment with cold.
After treatment, no noticeable changes to the subcutaneous fat. But 3 days later, there was an appearance of an inflammation-infiltrating infiltrate was noticed. The amount of inflammation cells was increased when the study was conducted between seven and fourteen days after treatment. After 30 days, the inflammation began to decrease after 60 days. The size of the interlobular septa was evident to have was increasing.
The inflammation was reduced even more after the 90-day period of. Researchers clearly proved that cryolipolysis causes panniculitis of the subcutaneous region because of cold exposure. This was followed by a reduction in its thickness within the fat layer without impacting the surrounding structures such as skin and tissues, which are water-rich. The findings of these research studies resulted in the development of an instrument called the Coolsculpting(tm) method (Zeltiq Aesthetics Inc., Pleasanton, CA) 30, 31 30 331. In the years since, research studies which have used this device have used numbers from CIF to indicate how much heat was that is extracted. It is difficult to assess the outcomes of research general and those specific to those which have utilized Coolsculpting. The studies 20 and 32 just recently released data about the treatment’s temperature determined in degrees Celsius.
A study that focused on a distinct area of research (lipocryolysis) (lipocryolysis) – which used adipocyte suspensions isolated from Wistar rats that were exposed to temperatures of 8degC over either 10 or 25 minutes saw increased crystallization when the duration of the exposure was extended. Additionally, it was discovered that crystals disappeared when they were heated to temperature of room. (22degC) for two hours.
A subsequent study applied several temperature patterns (heating and cooling) in isolated rat adipocytes and observed an increase in the crystallization process when using contrast temperatures: heating-cooling-heating. The two processes of cooling as well as contrast temperatures, demonstrated the potential for triggering cell death of adipocytes via crystallization of lipids. This research led to the development of Lipocryo(r) technique (Clinipro, S.L. Barcelona, Spain), and it is vital to note that the method of contrast lipocryolysis involves to extract temperatures that range from to 3degC.
An account of a case about the patient who underwent an ice-cold therapy at -5degC with the Galeno device (South Korea) revealed, with the help of the ultrasound for diagnosis the reduction in the thickness of fat. The histological analysis of the tissues during abdominoplasty revealed significant loss of adipocytes.
In a study conducted by Sasaki and coworkers. In a research done by Sasaki and. al. 35. They employed 35 who used the Coolsculpting device, an instrument used to monitor temperature within the subcutaneous tissues within the region of treatment. They found that the temperature inside tissues decreased to as to as low at 9° Celsius.
Because research studies employ various nonsurgical devices to regulate cooling processes for reducing subcutaneous fat, without damaging the surrounding tissues and since they all employ temperatures that are different between the CIF index, and even up to 3degC , it’s hard to judge the effectiveness of studies.
The evidence is conclusive that freezing of lipids (crystal-structure formation) of adipocytes occurs at temperatures that range between 8degC and 10degC. It’s dependent on the temperature and time, and this is the reason for the results.
The study involved all participants. who were treated with Polarys(r) device. Polarys(r) instrument (Ibramed, Amparo, SP, Brazil) using the method described below: initial warming of 40degC in 10 minutes, followed by extraction of the temperature over 60 minutes (a cold temperature of -8°C is established within the device) before heating up to 40degC for 10 minutes following the cooling procedure. Extraction of heat from the skin creates the formation of a thermal gradient.
This is thought to be because the outer layer of the skin (skin skin’s surface) are cooler and they grow to the subcutaneous layers (adipose layer) as the process advances. The procedures were executed using devices that use vacuum pressure (medium or larger in size) to remove and warm the heat from both sides of the lengthening and reducing blood flow by vasoconstriction and compression of the tissues. The duration of procedure was approximately eight hours for each treatment zone. The patient was treated in three to 5 locations, including the abdomen or flanks, based on the needs of each individual. This procedure could be performed in just one session or in two.
In the course of treatment , the study didn’t show any significant change in the weight or BMI was observed. However, when contrasted with prior measures, the waist circumferences dramatically decreased in the 30-day and 60-day follow-ups. Also, the circumferences decreased between the 30-day and sixty-day following-ups. They did not differ. This was evident during follow-up of 90 days. In spite of the methodological accuracy, we suspect that a number of variables could be influencing the results taken during the follow-up period of 90 days. This contrasts to the measurements taken with a skinfold caliper as well as diagnostic ultrasound.
The metabolic stress caused by cold during treatments, as well as the production of reactive oxygen species during the postischemia reperfusion which occurs after the disengagement of the applicator have been the focus of research studies. Since the beginning, in both preclinical and clinical studies, treatment of massaging (1-5 length) was applied shortly after the procedure in order to ensure uniform crystallization in the area treated of the applicator. It is believed that reperfusion after cooling of tissue may cause the release of more active oxygen species (ROS) calcium levels in the cytosol, and trigger the activation of both dependent and independent the calcium proteolytic enzymes.
These include caspases that activate the apoptotic pathway. Our study revealed that the duration of the application included 10 minutes of heat up to 40°C in order to improve reperfusion. This may be the cause of our impressive results when compared to the results of other clinical studies using ultrasound to measure abdominal weight. Medians for the reductions in thickness of fat in these studies were 18.2 percent 24 and 19.5 percent 2829.6 percent] and 19.6 percent after 356 months of the treatment.
The study revealed that the median percentage reduction in the fat layer was 21.6 percent, measured after three months of treatments. These range of reductions between 50.1 percent to 50.1 percent. The results were seen at the start of the study as well as at three months. The results were beneficial for the flanks region. The median reduction rate was 14.5 percent. In addition, decreases between 14.5 percent and 43.2 percent were observed in the comparison of measurements from baseline and the three-month follow-up. Results can be seen in the images of comparison in.
Concerning the safety issue We did not notice an increase in fasting levels of glucose, lipids or glucose as well as tests to determine the function of liver (aspartate aminotransferase or Alanine aminotransferase) following cryolipolysis contrast treatments, as shown on the chart 1.. Results are similar to the results reported in the study by Klein as well, that used cryolipolysis for an established procedure. The reduction in adipocytes isn’t sufficient to affect the function of the liver or levels of serum lipids.
The study comprised 84 sites that which were treated by cryolipolysis. In contrast. 54 were treated with an applicator with a medium size 30 of them were treated using the largest applicator. The subjects experienced minor to moderate discomfort in the region treated in the contrast phase. However the procedure was embraced by 95 percent of the participants. The most common adverse effects of cryolipolysis which have been observed in clinical studies include bruises and edema caused by erythema or intermittent pain 40]. The participants experienced a few negative reactions, which included small bruising, redness, and numbness, which went away by themselves. The subjects did not suffer from burning or pain as a result of neuralgia.
Conclusion
Contrast cryolipolysis was efficient and safe in the treatment of small amounts of fat which are found around the stomach as well as the flanks. Although the study was conducted using larger number of patients than what was suggested by the estimation of the sample, we think that further research that involves a greater number of patients is required.