Simon Yoo

Efficacy and Safety of Vismodegib in Advanced Basal-Cell Carcinoma

BACKGROUND Alterations in hedgehog signaling are implicated in the pathogenesis of basal-cell carcinoma. Although most basal-cell carcinomas are treated surgically, no effective therapy exists for locally advanced or metastatic basal-cell carcinoma. A phase 1 study of vismodegib (GDC-0449), a first-in-class, small-molecule inhibitor of the hedgehog pathway, showed a 58% response rate among patients with advanced basal-cell carcinoma. METHODS In this multicenter, international, two-cohort, nonrandomized study, we enrolled patients with metastatic basal-cell carcinoma and those with locally advanced basal-cell carcinoma who had inoperable disease or for whom surgery was inappropriate (because of multiple recurrences and a low likelihood of surgical cure, or substantial anticipated disfigurement). All patients received 150 mg of oral vismodegib daily. The primary end point was the independently assessed objective response rate; the primary hypotheses were that the response rate would be greater than 20% for patients with locally advanced basal-cell carcinoma and greater than 10% for those with metastatic basal-cell carcinoma. RESULTS In 33 patients with metastatic basal-cell carcinoma, the independently assessed response rate was 30% (95% confidence interval [CI], 16 to 48; P=0.001). In 63 patients with locally advanced basal-cell carcinoma, the independently assessed response rate was 43% (95% CI, 31 to 56; P<0.001), with complete responses in 13 patients (21%). The median duration of response was 7.6 months in both cohorts. Adverse events occurring in more than 30% of patients were muscle spasms, alopecia, dysgeusia (taste disturbance), weight loss, and fatigue. Serious adverse events were reported in 25% of patients; seven deaths due to adverse events were noted. CONCLUSIONS Vismodegib is associated with tumor responses in patients with locally advanced or metastatic basal-cell carcinoma. (Funded by Genentech; Erivance BCC ClinicalTrials.gov number, NCT00833417.).

Ultrasound tightening of facial and neck skin: A rater-blinded prospective cohort study

BACKGROUND Nonablative skin tightening technologies offer the prospect of reduction of wrinkles and skin sagging with minimal downtime, discomfort, and risk of adverse events. The excellent safety profile is mitigated by the limited efficacy of such procedures. OBJECTIVE We sought to assess the efficacy of ultrasound skin tightening for brow-lift in the context of a procedure treating the full face and neck. METHODS This was a rater-blinded, prospective cohort study at a dermatology clinic in an urban academic medical center. Subjects were medicated with topical anesthetic and then treated with an investigational focused intense ultrasound tightening device to the forehead, temples, cheeks, submental region, and side of neck using the following probes: 4 MHz, 4.5-mm focal depth; 7 MHz, 4.5-mm focal depth; and 7 MHz, 3.0-mm focal depth. Standardized photographs of front and side views were obtained at 2, 7, 28, 60, and 90 days; rating scales of pain, adverse events, physical findings, and patient satisfaction were also completed. Primary outcome measure was detection of improvement in paired comparison of pretreatment and posttreatment (day 90) photographs by 3 masked expert physician assessors, cosmetic and laser dermatologists, and plastic surgeons who were not authors. Second primary outcome measure was objective brow elevation as quantitated by a standard procedure using fixed landmarks. Secondary outcomes measure was patient satisfaction as measured by a questionnaire. RESULTS A total of 36 subjects (34 female) were enrolled, one subject dropped out, and 35 subjects were evaluated. Median age was 44 years (range 32-62). On the first primary outcome measure, 30 of 35 subjects (86%) were judged by the 3 masked experienced clinician raters to show clinically significant brow-lift 90 days after treatment (P = .00001). On the second primary outcome measure, mean value of average change in eyebrow height as assessed by measurement of photographs at 90 days was 1.7 mm. LIMITATIONS Limitations of this study include the inability to quantitatively measure lower face tightening because of the lack of fixed anatomic landmarks in this area. CONCLUSION Ultrasound appears to be a safe and effective modality for facial skin tightening. A single ultrasound treatment of the forehead produced on average brow height elevation of slightly less than 2 mm. Most treated individuals responded, commonly with accompanying transitory mild erythema and edema.

Barbed sutures: A review of the literature

Background: Despite substantial mention in the popular press, there is little in the plastic surgery or dermatology literature regarding the safety, efficacy, longevity, or complications of barbed suture suspension procedures. The authors review the literature to estimate several clinical parameters pertaining to barbed thread suspensions. Methods: The authors performed a MEDLINE search using the keywords “barbed and suture,” “thread and suspension,” “Aptos,” “Featherlift,” and “Contour Thread.” Results: The authors identified six studies that met their criteria of addressing midface elevation with barbed thread suspension. These detected some adverse events, but most of these were minor, self-limited, and of short duration. Less clear are the data on the extent of the peak correction and the longevity of effect. Objective outcome measures and long-term follow-up data were not provided in a systematic manner in the few available studies. Conclusions: Suspension of the aging face with barbed sutures offers the promise of a minimally invasive technique with diminished adverse events. The technique is in its infancy, but it has potential to be a useful and effective clinical tool as further innovations are made in the clinic and laboratory.

Pivotal ERIVANCE basal cell carcinoma (BCC) study: 12-month update of efficacy and safety of vismodegib in advanced BCC

BACKGROUND Primary analysis from the pivotal ERIVANCE BCC study resulted in approval of vismodegib, a Hedgehog pathway inhibitor indicated for treatment of adults with metastatic or locally advanced basal cell carcinoma (BCC) that has recurred after surgery or for patients who are not candidates for surgery or radiation. OBJECTIVE An efficacy and safety analysis was conducted 12 months after primary analysis. METHODS This was a multinational, multicenter, nonrandomized, 2-cohort study in patients with measurable and histologically confirmed locally advanced or metastatic BCC taking oral vismodegib (150 mg/d). Primary outcome measure was objective response rate (complete and partial responses) assessed by independent review facility. RESULTS After 12 months of additional follow-up, median duration of exposure to vismodegib was 12.9 months. Objective response rate increased from 30.3% to 33.3% in patients with metastatic disease, and from 42.9% to 47.6% in patients with the locally advanced form. Median duration of response in patients with locally advanced BCC increased from 7.6 to 9.5 months. No new safety signals emerged with extended treatment duration. LIMITATIONS Limitations include low prevalence of advanced BCC and challenges of designing a study with heterogenous manifestations. CONCLUSION The 12-month update of the study confirms the efficacy and safety of vismodegib in management of advanced BCC.

Cupping: East meets West

Cupping is the technique whereby a localized vacuum applied against the skin breaks superficial blood vessels in the papillary dermis, thereby creating distinctive circular cutaneous lesions. It is used mainly in Asia as an alternative therapy for a variety of ailments, and dermatologists, as skin specialists, should be able to recognize the unique morphology resulting from this procedure. Cupping can be accomplished by several techniques. Older methods employ the use of alcohol-soaked cotton at the base of brass, steel, or glass cups, which is subsequently lit on fire. 1

The use of brachytherapy in the treatment of nonmelanoma skin cancer: A review

Nonmelanoma skin cancers can be treated by various modalities, including electrodessication and curettage, excisional techniques, and radiation. In selected cases, radiation may be preferable to surgery. When radiation is an option, brachytherapy, a form of radiation therapy that places the radiation source close to the area to be treated, may have advantages relative to conventional external beam radiation in particular patients. After brachytherapy, recurrence rates for nonmelanoma skin cancers are low, especially for small, superficial lesions, with good to excellent functional and cosmetic results. This article reviews the indications, efficacy, and adverse effects of brachytherapy in the treatment of nonmelanoma skin cancers.

Adverse Events Associated With Mohs Micrographic Surgery Multicenter Prospective Cohort Study of 20 821 Cases at 23 Centers

IMPORTANCE Detailed information regarding perioperative risk and adverse events associated with Mohs micrographic surgery (MMS) can guide clinical management. Much of the data regarding complications of MMS are anecdotal or report findings from single centers or single events. OBJECTIVES To quantify adverse events associated with MMS and detect differences relevant to safety. DESIGN, SETTING, AND PARTICIPANTS Multicenter prospective inception cohort study of 21 private and 2 institutional US ambulatory referral centers for MMS. Participants were a consecutive sample of patients presenting with MMS for 35 weeks at each center, with staggered start times. EXPOSURE Mohs micrographic surgery. MAIN OUTCOMES AND MEASURES Intraoperative and postoperative minor and serious adverse events. RESULTS Among 20 821 MMS procedures, 149 adverse events (0.72%), including 4 serious events (0.02%), and no deaths were reported. Common adverse events reported were infections (61.1%), dehiscence and partial or full necrosis (20.1%), and bleeding and hematoma (15.4%). Most bleeding and wound-healing complications occurred in patients receiving anticoagulation therapy. Use of some antiseptics and antibiotics and sterile gloves during MMS were associated with modest reduction of risk for adverse events. CONCLUSIONS AND RELEVANCE Mohs micrographic surgery is safe, with a very low rate of adverse events, an exceedingly low rate of serious adverse events, and an undetectable mortality rate. Common complications include infections, followed by impaired wound healing and bleeding. Bleeding and wound-healing issues are often associated with preexisting anticoagulation therapy, which is nonetheless managed safely during MMS. We are not certain whether the small effects seen with the use of sterile gloves and antiseptics and antibiotics are clinically significant and whether wide-scale practice changes would be cost-effective given the small risk reductions.

Clinicopathologic features of ulcerative-atrophic sarcoidosis.

Background  Sarcoidosis is a chronic granulomatous disease of unknown etiology. Cutaneous disease is common and includes two clinicopathologic categories: granulomatous infiltration or a reactive phenomenon. In the granulomatous infiltrative group, clinical manifestations can be variable. Ulcers in sarcoidosis are uncommonly recognized and have been categorized previously under the rubric of atrophic, necrobiosis‐like, or ulcerative sarcoidosis.

Accelerated resolution of laser‐induced bruising with topical 20% arnica: a rater‐blinded randomized controlled trial

Background  Dermatological procedures can result in disfiguring bruises that resolve slowly.

Comparative effectiveness of nonpurpuragenic 595-nm pulsed dye laser and microsecond 1064-nm neodymium:yttrium-aluminum-garnet laser for treatment of diffuse facial erythema: A double-blind randomized controlled trial

BACKGROUND Facial erythema is a common symptom that responds to vascular laser treatment, but there are few comparative studies. OBJECTIVE We sought to compare the effectiveness of microsecond 1064-nm neodymium:yttrium-aluminum-garnet (Nd:YAG) laser with nonpurpuragenic 595-nm pulsed dye laser (PDL) for diffuse facial erythema. METHODS This was a split-face, double-blind randomized controlled trial. Bilateral cheeks received 4 treatments each at one month intervals with PDL or Nd:YAG. Spectrophotometer measurements, digital photographs, pain scores, and patient preferences were recorded. RESULTS Sixteen patients enrolled and 2 dropped out. Fourteen patients, all skin types I to III, 57% women, mean age 42 years, completed the study and were analyzed. Spectrophotometer readings changed after both PDL (8.9%) and Nd:YAG (2.5%), but varied by treatment type, with PDL reducing facial redness 6.4% more from baseline than Nd:YAG (P = .0199; 95% confidence interval -11.6 to -1.2). Pain varied (P = .0028), with Nd:YAG associated with less pain, at 3.07, than PDL at 3.87. Subjects rated redness as improved by 52% as a result of PDL, and 34% as a result of Nd:YAG (P = .031; 95% confidence interval -34.6 to -1.94). No serious adverse events were observed. LIMITATIONS Lasers settings are not standardized across devices. CONCLUSION Facial erythema is safely and effectively treated with PDL and Nd:YAG. Nonpupuragenic PDL may be more effective for lighter-skinned patients, but microsecond Nd:YAG may be less painful.