Collagenase Clostridium Histolyticum-aaes for Treatment of Cellulite: A Pooled Analysis of Two Phase-3 Trials.

Background: Collagen-rich fibrous septae and subcutaneous adipose protrusions play a role in cellulite pathophysiology. Collagenase clostridium histolyticum-aaes (CCH-aaes) injection causes enzymatic release of septae to resolve cellulite depressions and create a skin smoothing effect. This analysis pooled data from two identically designed, phase-3, randomized, double-blind, placebo-controlled studies to examine the efficacy and safety of CCH-aaes. Methods: Adult women with moderate/severe cellulite (3-4 on Clinician Reported Photonumeric Cellulite Severity Scale and Patient Reported Photonumeric Cellulite Severity Scale) on the buttocks received up to three treatment sessions (Days 1, 22, and 43) of subcutaneous CCH-aaes 0.84 mg or placebo per treatment area. Composite and individual component response (≥2-level or ≥1-level improvement from baseline in Patient Reported Photonumeric Cellulite Severity Scale and/or Clinician Reported Photonumeric Cellulite Severity Scale) and additional patient-reported outcomes were determined at Day 71. Results: Analysis included 424 CCH-aaes-treated and 419 placebo-treated women. CCH-aaes-treated women were 5.9 times more likely than placebo-treated women to be ≥2-level composite responders at Day 71 (odds ratio [95% confidence interval], 5.9 [2.2-15.4]; P < 0.001). A significantly greater percentage of CCH-aaes-treated women versus placebo-treated women were ≥1-level composite responders at Day 71 (39.4% versus 14.6%; P < 0.001). Subgroup analyses indicated no apparent impact of Fitzpatrick skin type category and baseline cellulite severity (moderate/severe) on CCH-aaes efficacy. An inverse relationship between age and CCH-aaes response was observed in those with a body mass index less than 32 kg per m2. The most common adverse events with CCH-aaes were injection-site bruising and injection-site pain. Conclusion: CCH-aaes treatment significantly improved moderate-to-severe buttock cellulite appearance and was generally well tolerated.

Collagenase Clostridium Histolyticum-aaes for the Treatment of Cellulite in Women: Results From Two Phase 3 Randomized, Placebo-Controlled Trials.

BACKGROUND: Fibrous septae play a role in contour alterations associated with cellulite. OBJECTIVE: To assess collagenase clostridium histolyticum-aaes (CCH) for the treatment of cellulite. MATERIALS AND METHODS: Two identically designed phase 3, double-blind, randomized studies (RELEASE-1 and RELEASE-2) were conducted. Adult women with moderate/severe cellulite (rating 3-4 on the Patient Reported Photonumeric Cellulite Severity Scale [PR-PCSS] and Clinician Reported PCSS [CR-PCSS]) on the buttocks received up to 3 treatment sessions of subcutaneous CCH 0.84 mg or placebo per treatment area. Composite response (≥2-level or ≥1-level improvement from baseline in both PR-PCSS and CR-PCSS) was determined at Day 71. RESULTS: Eight hundred forty-three women received ≥1 injection (CCH vs placebo: RELEASE-1, n = 210 vs n = 213; RELEASE-2, n = 214 vs n = 206). Greater percentages of CCH-treated women were ≥2-level composite responders versus placebo in RELEASE-1 (7.6% vs 1.9%; p = .006) and RELEASE-2 (5.6% vs 0.5%; p = .002) and ≥1-level composite responders in RELEASE-1 (37.1% vs 17.8%; p < .001) and RELEASE-2 (41.6% vs 11.2%; p < .001). Most adverse events (AEs) in the CCH group were injection site related; few CCH-treated women discontinued because of an AE (≤4.3%). CONCLUSION: Collagenase clostridium histolyticum-aaes significantly improved cellulite appearance and was generally well tolerated.

Comparison of Cellulite Severity Scales and Imaging Methods.

Cellulite is characterized by dimpled contour alterations of the skin and is present in approximately 85% to 90% of postpubertal females. Although the pathophysiology of cellulite remains to be fully elucidated, experimental evidence indicates a multifactorial process involving the number and types of fibrous septae, microvascular dysfunction, subcutaneous inflammation, decreased dermal thickness with age, and fat deposition. Cellulite is a major cosmetic concern for many women, and a number of both noninvasive (eg, massage, cosmeceuticals, laser therapy) and minimally invasive techniques (eg, subcision, collagenase injection) have been evaluated to improve the appearance of the affected skin. However, evidence for many of these treatments is limited, largely due to the lack of a validated, convenient tool for the standardized evaluation of cellulite severity. Various imaging modalities have been employed to characterize cellulite severity and the impact of treatment, but only 2-dimensional and 3-dimensional digital photography have been adequately validated. However, in many cases, imaging findings do not correlate with subjective measures of cellulite severity. A number of cellulite rating scales have been developed; some provide only a qualitative measure, whereas others do not fully capture all clinically relevant aspects of cellulite, including the perspective of the patient. There remains an unmet need for global adoption of a validated scale that can be utilized easily by clinicians and patients in clinical and research settings. We propose features that should be included in an ideal rating scale for assessment of cellulite severity.

Collagenase Clostridium Histolyticum for the Treatment of Edematous Fibrosclerotic Panniculopathy (Cellulite): A Randomized Trial.

BACKGROUND: Edematous fibrosclerotic panniculopathy (EFP; cellulite) is associated with thickening and contraction of collagen-rich subdermal septae. Collagenase clostridium histolyticum (CCH) may disrupt collagen-rich septae. OBJECTIVE: To evaluate the safety and efficacy of CCH for treatment of EFP. MATERIALS AND METHODS: In a randomized, double-blind study, women with moderate or severe EFP of the buttocks or posterolateral thighs (i.e., Clinician Reported Photonumeric Cellulite Severity Scale [CR-PCSS] and Patient Reported Photonumeric Cellulite Severity Scale [PR-PCSS] ratings of 3 to 4, and Hexsel Cellulite Severity Scale score ≤13) received up to 3 treatment sessions (Days 1, 22, and 43) of subcutaneous CCH 0.84 mg or placebo injections. End points included the percentage of 2-level and 1-level composite responders (i.e., had ≥2-level or ≥1-level improvement in CR-PCSS and PR-PCSS) at Day 71. RESULTS: Three hundred seventy-five women (mean age, 46.5 years; 86.4% white) were randomly assigned to CCH (n = 189) or placebo (n = 186). At Day 71, the percentages of 2-level and 1-level composite responders were greater with CCH (10.6% and 44.6%, respectively) versus placebo (1.6% and 17.9%; p < .001 for both). The most common adverse events were injection-site related. CONCLUSION: CCH significantly improved EFP appearance versus placebo; further evaluation of CCH for EFP (cellulite) is warranted.

Breast Implants: Protocol for Retrieval and Analysis.

The Center for Implant Retrieval and Analysis has been established at Washington University's Division of Plastic and Reconstructive Surgery for the purpose of studying implantable devices retrieved after surgery or autopsy and assessing their condition after implantation. Since the early 1990s, significant experience has been gained in testing and analyzing silicone gel breast implants and, to a lesser extent, saline-filled devices. However, there has been no systematic method reported for collecting and evaluating these implants in a way that would permit di. erent laboratories to compare their data. This article offers the plastic and reconstructive surgery community a standardized protocol for analyzing explanted silicone gel and saline-filled breast implants. The protocol gives surgeons a clearly defined approach for removing, handling, documenting, and shipping explanted breast implants. At the same time, biomaterials researchers can use the protocol to acquire implant data with reliable and reproducible methods. Because the study of saline implants has lagged behind the study of silicone gel implants, the article concludes with a demonstration of how this protocol can be applied to obtain mechanical properties data and use scanning electron microscopy to illuminate failure mechanisms of saline devices, including three explants removed after 20+ years in vivo.

Antibiotic prophylaxis for preventing surgical-site infection in plastic surgery: an evidence-based consensus conference statement from the American Association of Plastic Surgeons.

BACKGROUND: There is a growing concern for microbial resistance as a result of overuse of antibiotics. Although guidelines have focused on the use of antibiotics for surgery in general, few have addressed plastic surgery specifically. The objective of this expert consensus conference was to evaluate the evidence for efficacy and safety of antibiotic prophylaxis in plastic surgical procedures. METHODS: THE AUTHORS: searched for existing high-quality systematic reviews for antibiotic prophylaxis in the literature from the MEDLINE, Cochrane Library, and Embase databases. All synonyms for antibiotics were combined with terms for relevant plastic surgery procedures. The searches were not limited by language, and included all study designs. In addition, supplemental hand searches were performed of bibliographies of relevant articles, and extensive "related articles." Meta-analyses were performed and reviewed by experts selected by the American Association of Plastic Surgeons to reach consensus recommendations. RESULTS: Database searches identified 4300 articles, from which 2042 full-text articles were identified for eligibility. De novo meta-analyses were performed for each plastic surgical category. In total, 67 studies met the inclusion criteria, including nine for breast surgery, 17 for head and neck surgery, 10 for orthognathic surgery, seven for rhinoplasty/septoplasty, 19 for hand surgery, five for skin surgery, and two for abdominoplasty. CONCLUSIONS: Systemic antibiotic prophylaxis is recommended for clean breast surgery and for contaminated surgery of the hand or the head and neck. It is not recommended to reduce infection in clean surgical cases of the hand, skin, head and neck, or abdominoplasty.

An evaluation of the patient population for aesthetic treatments targeting abdominal subcutaneous adipose tissue.

A large and growing population of patients currently seeks minimally invasive therapeutic options for the aesthetic treatment of localized, central abdominal subcutaneous adipose tissue (SAT). We sought to evaluate the ideal population for aesthetic treatment of central abdominal SAT, highlight the existing disparities between SAT in obese (body mass index [BMI] ≥ 30; BMI) and nonobese (BMI < 30) patients, and review the available FDA-cleared, minimally invasive treatment options for central abdominal adiposity. The cosmetic issue of localized, central (periumbilical) abdominal adiposity in nonobese individuals is quite distinct from abdominal bulging secondary to obesity. Given the recognized clinical and physiologic differences between obese and nonobese counterparts, the exclusion of obese patients from clinical study by currently available FDA-cleared devices targeting abdominal fat, and the status of obesity as a chronic, systemic disease requiring medical, surgical, and/or lifestyle-altering therapies, minimally invasive therapeutic options for aesthetic reductions in central abdominal SAT must be limited to the nonobese population.

Trends in autologous fat grafting to the breast: a national survey of the american society of plastic surgeons.

BACKGROUND: Autologous fat grafting has been gaining popularity in recent years, although there remains concern regarding the safety and efficacy of the practice for breast surgery. The purpose of this study was to determine national trends for fat grafting to the breast and to establish the frequency and specific techniques of the procedure to provide more supportive data. METHODS: A questionnaire was e-mailed to 2584 members of the American Society of Plastic Surgeons. Variables included prevalence and applications of fat grafting to the breast. Components of the fat graft protocol were also assessed. RESULTS: Four hundred fifty-six of the 2584 questionnaires were completed. Sixty-two percent of all respondents reported currently using fat grafting for reconstructive breast surgery and 28% of all respondents reported currently using the practice for aesthetic breast surgery. The most common reason cited by respondents for using fat grafting to the breast was as an adjunctive therapy to implant or flap surgery. CONCLUSIONS: Fat grafting to the breast is a common procedure most often used in reconstructive operations. The increasing prevalence of fat grafting to the breast indicates a need for collection of clinical data and supports the establishment of a national prospective registry to track outcomes after aesthetic and reconstructive applications.

Metabolic and structural effects of phosphatidylcholine and deoxycholate injections on subcutaneous fat: a randomized, controlled trial.

BACKGROUND: Phosphatidylcholine and deoxycholate (PC-DC) injections are a popular nonsurgical method to eliminate unwanted fat. The safety and efficacy of this approach is uncertain. OBJECTIVE: The authors evaluate the effects of PC-DC treatments on body composition, adipocyte function, and mechanisms responsible for fat loss. METHODS: This randomized, open-label study enrolled 13 women with a body mass index (BMI) ≤30 kg/m(2) and lower abdominal subcutaneous fat suitable for small-volume liposuction. Patients were randomized by the final digit of their Social Security numbers and received between 2 and 4 PC-DC treatments, spaced 8 weeks apart. One side below the umbilicus was injected with PC-DC. The contralateral, control side received no treatment. Adipose tissue biopsies were performed on the treated side at baseline, 1 week after the first treatment, and 8 weeks after the final treatment. The primary outcome was change in adipose tissue thickness at baseline and 8 weeks after the final treatment. RESULTS: Seven women completed the study. Treatment with PC-DC significantly reduced the thickness of the anterior subcutaneous abdominal fat (P = .004). Adipose tissue showed rapid increases in crown-like structures, macrophage infiltration, and reduced expression of leptin, hormone-sensitive lipase, adipose tissue triglyceride lipase, and CD36. Plasma C-reactive protein, lipid profile, and plasma glucose concentrations were unchanged. CONCLUSIONS: PC-DC injections can effectively reduce abdominal fat volume and thickness by inducing adipocyte necrosis. These treatments do not appear to increase circulating markers of inflammation or affect glucose and lipid metabolism.

Recommendations on clinical proof of efficacy for potential scar prevention and reduction therapies.

Cutaneous scarring is an enormous medical problem with approximately 100 million patients acquiring scars each year. Scar prevention/reduction represents a significant, and largely unmet, clinical need. Research into the prophylactic modulation of scar outcome differs from research into other disease processes as the scar is not present at the start of the study; measurements of changes from baseline are impossible. Final scar morphology is influenced by many variables. A fundamental principle that should be observed in the prospective evaluation of scar prevention/reduction therapies is that, if left untreated, wounds in treatment and control groups should have healed with identical scars. Observation of this principle will allow the detection of true treatment effects. The many variables that influence scar morphology mean that the evaluation of potential pharmaceutical products for this indication favors the use of self-controlled designs in clinical trials. In this article, we review variables that affect scar morphology and recommend the self-controlled design for clinical trials aiming to establish proof of efficacy of scar prevention and reduction pharmaceuticals. With no pharmaceutical products currently licensed for this indication, this represents a new therapeutic area. The principles discussed will also have direct relevance to the wider fields of wound healing and regenerative medicine.

Anaplastic large cell lymphoma and breast implants: results from a structured expert consultation process.

BACKGROUND: There are increasing concerns about a possible association between anaplastic large cell lymphoma (ALCL) and breast implants. The authors conducted a structured expert consultation process to evaluate the evidence for the association, its clinical significance, and a potential biological model based on their interpretation of the published evidence. METHODS: A multidisciplinary panel of 10 experts was selected based on nominations from national specialty societies, academic department heads, and recognized researchers in the United States. RESULTS: Panelists agreed that (1) there is a positive association between breast implants and ALCL development but likely underrecognition of the true number of cases; (2) a recurrent, clinically evident seroma occurring 6 months or more after breast implantation should be aspirated and sent for cytologic analysis; (3) anaplastic lymphoma kinase-negative ALCL that develops around breast implants is a clinically indolent disease with a favorable prognosis that is distinct from systemic anaplastic lymphoma kinase-negative ALCL; (4) management should consist of removal of the involved implant and capsule, which is likely to prevent recurrence, and evaluation for other sites of disease; and (5) adjuvant radiation or chemotherapy should not be offered to women with capsule-confined disease. Little agreement, however, was found regarding etiologic risk factors for implant-associated ALCL. CONCLUSION: The authors' assessment yielded consistent results on a number of key issues regarding ALCL in women with breast implants, but substantial further research is needed to improve our understanding of the epidemiology, clinical aspects, and biology of this disease. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, V.

Anaplastic large cell lymphoma and breast implants: a systematic review.

BACKGROUND: In recent years, there have been growing concerns about a possible association of non-Hodgkin's lymphoma--in particular, anaplastic large cell lymphoma (ALCL)--and breast implants. The purpose of this study was to identify and analyze all reported cases of non-Hodgkin's lymphoma occurring in patients with breast implants. METHODS: The authors conducted a systematic literature review of reported cases of non-Hodgkin's lymphoma in patients with breast implants. Publications were identified with a search algorithm, forward searches, and expert nominations. After references were reviewed and assessed for inclusion or exclusion, case-based data were independently abstracted, reconciled, and adjudicated by multiple investigators. The data were then synthesized and analyzed. RESULTS: Of 884 identified articles, only 83 were relevant to non-Hodgkin's lymphoma involving the breast, and 34 were included in our study. Thirty-six cases of non-Hodgkin's lymphoma in patients with implants were found, of which 29 (81 percent) were ALCLs. Although detailed clinical information was lacking in many cases, ALCL often involved the capsule and/or presented as an unexplained seroma or mass, was negative for anaplastic lymphoma kinase (ALK) expression, and had a relatively indolent clinical course when it developed adjacent to a breast implant. CONCLUSIONS: A form of ALCL, which clinically behaves more like the less aggressive primary cutaneous form of ALK-negative ALCL rather than the more aggressive systemic form, may be associated with breast implants. Future research on the epidemiology and biology of this rare disease is clearly needed to better understand its nature.

Prophylactic antibiotics in aesthetic surgery.

Improvements in infection prevention practices over the past several decades have enhanced outcomes following aesthetic surgery. However, surgical site infections (SSI) continue to result in increased morbidity, mortality, and cost of care. The true incidence rate of SSI in aesthetic surgery is unknown due to the lack of a national surveillance system, but studies of SSI across surgical specialties have suggested that many of these infections are preventable. Patient-related factors-including obesity, glycemic control, and tobacco use-may contribute to the development of SSI following aesthetic surgery. In terms of SSI prevention, proper handwashing and surgical skin preparation are integral. Furthermore, the administration of prophylactic antibiotics has been shown to reduce SSI following many types of surgical procedures. Unfortunately, there are few large, randomized studies examining the role of prophylactic antibiotics in aesthetic surgery. The authors review the medical literature, discuss the risks of antibiotic overutilization, and detail nonpharmacological methods for reducing the risk of SSI.

Hereditary coagulopathies: practical diagnosis and management for the plastic surgeon.

BACKGROUND: Venous thromboembolism is a devastating complication representing one of the major causes of postoperative death in plastic surgery. Within the scope of plastic surgery, body-contouring procedures are often considered to carry a higher risk of venous thromboembolism. Hereditary thrombophilias comprise a group of conditions defined by a genetic predisposition to thrombosis development. Collectively, hereditary thrombophilias are present in at least 15 percent of Western populations and underlie approximately half of thromboembolic events. Although the topic of venous thromboembolism is discussed widely throughout the literature, there is little published on the diagnosis and management of hereditary thrombophilias in the plastic surgery literature. The goals of this study were to present a review of the major inherited thrombophilias, to delineate the risk of these disorders, and to recommend a practical algorithm for patient screening and management before major plastic surgery. METHODS: A MEDLINE search was performed from 1965 to the present to review the literature on inherited thrombophilia disorders. RESULTS: Based on the English language literature and clinical experience, the authors suggest practical guidelines for screening and management of hereditary thrombophilias. A thorough medical history and preoperative evaluation are key to reducing venous thromboembolism complications. CONCLUSIONS: Hereditary thrombophilias are present in a significant number of thromboembolic events. Preoperative vigilance on the part of the plastic surgeon may help to identify patients with undiagnosed hereditary thrombophilias and thereby decrease the incidence of venous thromboembolism.

Methicillin-sensitive and methicillin-resistant Staphylococcus aureus: preventing surgical site infections following plastic surgery.

LEARNING OBJECTIVES: The reader is presumed to have a broad understanding of aesthetic surgical procedures. After studying this article, the participant should be able to: 1. Explain the microbiology of Staphylococcus species and discuss antibiotic resistance development in Staphylococcus species and assess how clinical outcomes are affected. 2. Identify the epidemiology of Staphylococcus carriers and the impact on the clinical practice and regulation. Practice effective measures that prevent surgical site infections. 3. Practice screening for and decolonizing of patients with methicillin-resistant Staphylococcus aureus (MRSA). Physicians may earn 2.5 AMA PRA Category 1 Credit by successfully completing the examination based on material covered in this article. The examination begins on page 245. As a measure of the success of the education we hope you will receive from this article, we encourage you to log on to the Aesthetic Society website and take the preexamination before reading this article. Once you have completed the article, you may then take the examination again for CME credit. The Aesthetic Society will be able to compare your answers and use this data for future reference as we attempt to continually improve the CME articles we offer. ASAPS members can complete this CME examination online by logging on to the ASAPS Members-Only Website (http://www.surgery.org/members) and clicking on "Clinical Education" in the menu bar. Staphylococcus aureus is the most common cause of surgical site infections (SSI), with both methicillin-sensitive and methicillin-resistant strains causing these infections. The incidence of methicillin-resistant S aureus (MRSA) has increased in the US over the past decade, largely due to the emergence of community-acquired MRSA (CA-MRSA). This article reviews the microbiology and epidemiology of methicillin-sensitive S aureus (MSSA) and MRSA, risk factors for surgical site infections among plastic surgery patients, the evidence supporting preoperative screening and decolonization measures to prevent surgical site infections caused by MRSA, recommendations for anti-microbial prophylaxis, and treatment recommendations for surgical site infections. Other proven methods of reducing SSI, including maintenance of normothermia during surgery, glucose control, cessation of nicotine use, and not shaving the surgical site preoperatively are discussed.

Insights into patient and clinician concerns about scar appearance: semiquantitative structured surveys.

BACKGROUND: Few data are available regarding the psychological impact of scars arising from routine elective/aesthetic surgical procedures. To gain insight into both patients' and clinicians' concerns, the authors have undertaken structured semiquantitative surveys of (1) patients who had recently undergone a routine surgical procedure and (2) a cohort of plastic and aesthetic dermatological surgeons. METHODS: All selected patients had undergone a surgical procedure within 6 to 24 months before survey and had a scar(s) that caused concern. Participants completed a previously validated Self Completion Form that aimed to investigate their concerns. Clinicians were surveyed via telephone interviews using a similar format of questionnaire but with questions tailored to clinicians. RESULTS: Ninety-seven patients and 24 clinicians were interviewed. Patients were dissatisfied with scars resulting from surgery, irrespective of gender, age, ethnicity, or geographical location, and 91 percent would value even small improvements in scarring. Patients had scar(s) that they wished were less noticeable over a wide range of body sites (both "visible" and "nonvisible"). Male and female respondents had similar rates of dissatisfaction about their own scars. The survey revealed issues in the communication between patients and clinicians regarding scars; 71 percent of patients felt that they were more concerned than their surgeon about the scar resulting from a recent surgical procedure. CONCLUSIONS: This preliminary study indicates that patients are highly concerned about scarring following routine surgery, with most patients valuing any improvement in scarring. These data also show that there are disparities in patient-clinician communication regarding expectations following surgery.

A new approach for the prophylactic improvement of surgical scarring: avotermin (TGF beta 3).

Patients and physicians are concerned about scarring resulting from surgery, and patients, in particular, value even small improvements in scarring. Translational research into the processes involved in scarring at the molecular, cellular, and tissue levels has facilitated the discovery and development of new biological approaches for improving scarring. This article highlights research concerning avotermin (human recombinant TGF beta 3), the first in a new class of prophylactic medicines that may promote the regeneration of normal skin and improve scar appearance.