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Summary Background Vismodegib, a first-in-class Hedgehog-pathway inhibitor, is approved for use in adults with advanced basal-cell carcinoma. Patients with multiple basal-cell carcinomas, including those with basal-cell nevus (Gorlin) syndrome, need extended treatment. We assessed the safety and activity of two long-term intermittent vismodegib dosing regimens in patients with multiple basal-cell carcinomas. Methods In this randomised, regimen-controlled, double-blind, phase 2 trial, we enrolled adult patients with multiple basal-cell carcinomas, including those with basal-cell nevus syndrome, who had one or more histopathologically confirmed and at least six clinically evident basal-cell carcinomas. From a centralised randomisation schedule accessed via an interactive voice or web-based response system, patients were randomly assigned (1:1) to treatment group A (150 mg oral vismodegib per day for 12 weeks, then three rounds of 8 weeks of placebo daily followed by 12 weeks of 150 mg vismodegib daily) or treatment group B (150 mg oral vismodegib per day for 24 weeks, then three rounds of 8 weeks of placebo daily followed by 8 weeks of 150 mg vismodegib daily). Treatment assignment was stratified by diagnosis of basal-cell nevus syndrome, geographical region, and immunosuppression status. The primary endpoint was percentage reduction from baseline in the number of clinically evident basal-cell carcinomas at week 73. The primary analysis was by intention to treat. The safety population included all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT01815840, and the study is ongoing. Findings Between April 30, 2013, and April 9, 2014, 229 patients were randomly assigned treatment, 116 in treatment group A and 113 in treatment group B. The mean number of basal-cell carcinoma lesions at week 73 was reduced from baseline by 62·7% (95% CI 53·0–72·3) in treatment group A and 54·0% (43·6–64·4) in treatment group B. 216 (95%) of 227 patients included in the safety analysis had at least one treatment-emergent adverse event deemed to be related to study treatment (107 [94%] of 114 in treatment group A and 109 [97%] of 113 in treatment group B). The most common grade 3 or worse treatment-related adverse events were muscle spasms (four [4%] patients in treatment group A vs 12 [11%] in treatment group B), increased blood creatine phosphokinase (one [1%] vs four [4%]), and hypophosphataemia (zero vs three [3%]). Serious treatment-emergent events were noted in 22 (19%) patients in treatment group A and 19 (17%) patients in treatment group B. Four (2%) patients died from adverse events; one (pulmonary embolism in treatment group A) was possibly related to treatment. Interpretation Both intermittent dosing schedules of vismodegib seemed to show good activity in long-term regimens in patients with multiple basal-cell carcinomas. Further study is warranted. Funding F Hoffmann-La Roche.

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Photodynamic therapy (PDT) utilizes a sensitizer agent and light to produce selective cell death. Dermatologists are familiar with PDT for the treatment of actinic keratoses and early nonmelanoma skin cancers, and recent studies have elucidated that PDT has resulted in improved morbidity and secondary outcomes for the treatment of various cancerous and precancerous solid tumors. Light source and dosimetry may be modified to selectively target tissue, and novel techniques such as fractionation, metronomic pulsation, continuous light delivery, and chemophototherapy are under investigation for further optimization of therapy. This article aims to review the expanding indications for PDT and demonstrate the potential of this modality to decrease morbidity and increase quality of life for patients. To illustrate these new indications, we provide a focused review of the latest literature on PDT for dermatologic and other solid tumors including gastrointestinal, peritoneal, lung, genitourinary, brain, breast, and head and neck. Data on efficacy, survival, and side effects vary across tumor types but support PDT for the treatment of numerous solid tumors. With new advances in PDT, indications for this therapeutic modality may expand.

Background Cyanoacrylate tissue adhesives are not more likely to result in wound dehiscence or infection than sutured closures. However, suturing is the gold standard for optimal cosmetic appearance of scars. Objective To determine whether cyanoacrylate tissue adhesives produce a cosmetic outcome equivalent to sutures at 3 months. Secondary outcomes include time for wound closure, time spent on wound care, and surgeon and patient satisfaction. Materials and methods Seventy-one patients scheduled for skin cancer excision at Beverly Hospital were included in this prospective, randomized, single-blind study. Cosmetic appearance was assessed by a masked panel of dermatologists and plastic surgeons who evaluated digital photographs. Secondary outcomes were assessed by nursing recordings and patient and surgeon evaluations. Results There was no significant difference in wound appearance (Visual Analog Scale: p = .4693, modified Hollander Wound Evaluation Score: p = .6413) between adhesives and sutures. It was faster and easier for a surgeon to use adhesives, and subjects spent less time caring for and were more satisfied by wounds sealed with adhesives than sutures. Conclusion Cyanoacrylate tissue adhesives produce cosmetic outcomes that are not statistically significantly different than sutures; furthermore, they are associated with fast application, easy wound care, and patient satisfaction.

Background Photodynamic therapy (PDT) is a binary therapy using a drug and high-energy light source. PDT is approved for several premalignant and malignant conditions. Recent in-vitro and animal data suggest that enhanced tumor-specific cytotoxicity can be achieved with far less collateral damage to normal surrounding tissues if PDT is administered continuously at a lower dose rate for extended periods of time. Based on these promising preclinical data, we conducted a Phase I clinical trial of continuous low-irradiance photodynamic therapy (CLIPT) using 630 nm laser energy and intravenously administered porforin sodium as the photosensitizer. We determined the maximum tolerated dose (MTD) of CLIPT on skin and tumor response in subjects with cutaneous and subcutaneous metastatic nodules who had failed radiation and surgery. Methods Patients with cutaneous and/or subcutaneous metastatic nodules that had failed radiation and surgery were offered enrollment into the trial. The initial study design planned for sequential cohorts of six subjects to be treated at increasing laser intensity, starting at 100 J/cm2 administered continuously over 24 h (10−2 dose rate compared with standard PDT). Dose-limiting toxicity was defined as partial or full-thickness necrosis of the surrounding tumor-free, previously irradiated skin. The MTD was defined as the highest laser energy at which ≤33% of subjects experienced the dose-limiting toxicity. Subjects received intravenous porfirmer sodium 0.8 mg/kg 48 h before commencing CLIPT. Response rates and quality of life measures were assessed. Results Nine subjects were enrolled with chest wall progression of breast cancer following mastectomy. All had failed prior surgery and electron-beam radiation therapy. The initial two subjects were treated at 100 J/cm2 and developed partial thickness skin necrosis. Dose reduction was therefore instituted, and the next cohort was treated at 50 J/cm2. None of the subsequent seven subjects suffered partial or full thickness necrosis, thus establishing the MTD at 50 J/cm2 over 24 h (0.5 mW irradiance). Six of the nine subjects (67%) had either a complete or partial clinical response. Of note, two subjects had significant regression of tumor nodules distant from the treatment field. Of the eight subjects whose terminal deoxynucleotidyl transferase dUTP nick end labeling assay results were available, 8 (100%) demonstrated histologic response to treatment as evidenced by either tumor apoptosis or regression. Quality of life measures were improved following treatment—particularly bleeding and pain from the tumor nodules. Conclusions The MTD of CLIPT was established at 50 J/cm2 administered continuously over 24 h. These preliminary data suggest CLIPT may be an effective, low-morbidity therapeutic modality in the treatment of cutaneous and subcutaneous metastases of breast cancer following mastectomy. Further evaluation in a larger cohort is warranted to better assess efficacy and optimize the intervention.

Plasmonic nanomaterials including gold nanorods are effective agents for inducing heating in tumors. Because near-infrared (NIR) light has traditionally been delivered using extracorporeal sources, most applications of plasmonic photothermal therapy have focused on isolated subcutaneous tumors. For more complex models of disease such as advanced ovarian cancer, one of the primary barriers to gold nanorod-based strategies is the adequate delivery of NIR light to tumors located at varying depths within the body. To address this limitation, a series of implanted NIR illumination sources are described for the specific heating of gold nanorod-containing tissues. Through computational modeling and ex vivo studies, a candidate device is identified and validated in a model of orthotopic ovarian cancer. As the therapeutic, imaging, and diagnostic applications of plasmonic nanomaterials progress, effective methods for NIR light delivery to challenging anatomical regions will complement ongoing efforts to advance plasmonic photothermal therapy toward clinical use.

Background Immunohistochemistry (IHC) applied to Mohs micrographic surgery (MMS) is time consuming and labor intensive, and the variability of staining quality has prevented its widespread use in clinical practice. Objective To investigate the readability of immunostains processed by a novel automated 16-minute technique used for evaluation of frozen sections prepared during MMS for melanoma. Methods A rapid automated instrument that performs MART-1 (melanoma antigen recognized by T cells) immunostains in 16 minutes was used to stain frozen sections and was compared with MART-1 stains of paraffin (permanent) sections, hematoxylin-eosin (H&E) stains of frozen and permanent sections from the positive or negative control specimens of the Mohs layers for melanoma. A total of 480 interpretations from 48 sections (4 types of stains for each specimen, 12 specimens read by 10 interpreters) were analyzed via blinded examination by 5 dermatopathologists and 5 Mohs surgeons at two institutions. A scoring system was used to assess the readability of each slide. Analysis of variance was used for statistical analysis. Results In terms of clarity of interpreting melanoma sections, the 16-minute MART-1 IHC of frozen sections is equivalent to the standard MART-1 of permanent sections. The 16-minute MART-1 sections are also significantly easier to interpret than permanent sections stained with H&E for both the dermatopathologists and Mohs surgeons ( P Limitations The study represents data collected from only two institutions in the United States. Conclusion The rapid-stained frozen IHC sections are significantly easier to interpret than the "gold standard" permanent sections stained with H&E. This technology facilitates the rapid interpretation of melanoma in frozen sections.

BACKGROUND Perineural invasion (PNI) by cutaneous squamous cell carcinoma (CSCC) and basal cell carcinoma (BCC) is an infrequent but not rare complication of traditionally low-morbidity skin cancers that can lead to catastrophic sequelae; 2.5% to 14% of CSCC and approximately 3% of BCC exhibit PNI. Tumors with PNI tend to be larger, have greater subclinical extension, have a higher rate of recurrence, and have a greater risk of metastases. Tumors with PNI may result in major neurologic deficits. OBJECTIVE To review current recommendations for the management of PNI and to evaluate a treatment strategy involving excision using Mohs micrographic surgery (MMS) followed by adjunctive radiotherapy. MATERIALS AND METHODS Cases of PNI treated with MMS and radiotherapy were reviewed for recurrence, disease-free follow-up, and adverse events. RESULTS Twelve patients with incidental PNI treated with MMS and adjunctive radiotherapy are presented. After 3 to 32 months of follow-up, there had been no recurrences. Adverse events from radiotherapy were minor and self-limited. CONCLUSIONS The use of adjunctive radiotherapy in these patients remains controversial. When managing superficial skin tumors with PNI, a multidisciplinary team including a cutaneous surgeon and a radiation oncologist familiar with PNI is recommended.

BACKGROUND Wound closure devices include sutures, tissue adhesives, adhesive strips, and staples. Recent studies suggest no differences between various tissue adhesives and sutures for dehiscence, infection, and satisfaction when assessed by patients or surgeons. To date, no studies have investigated ClozeX (Clozex Medical LLC, Wellesley, MA, USA), a novel adhesive strip, for closure of surgical incisions. OBJECTIVE To compare surgical wounds repaired with ClozeX versus suture. METHODS A prospective, randomized study was conducted, in which 15 patients with surgical incisions were allocated to closure with ClozeX on half of the wound and monofilament suture on the other half. Physician satisfaction with blinded assessment, patient satisfaction, complication rates, and closure times were recorded. RESULTS Application with ClozeX was faster than with suture (p=.007). There were no complications in either group. Sixty-nine percent of the patients gave ClozeX a higher satisfaction score (p=.02). More physicians were satisfied with the ClozeX half than with the suture half (p=.007). CONCLUSIONS This pilot study demonstrates ClozeX to be a safe and effective closure device. The cosmetic outcome seems to be at least as good as simple running suture. Physicians and patients were generally more satisfied with ClozeX. No difference was found in the rate of dehiscence or infection between the groups.

Background. The current medical literature contains multiple different meanings for the term “local melanoma recurrence.” Confusion regarding locally persistent and locally metastatic disease makes interpretation and analysis of previously published reports difficult if not impossible. Objective. The objective was to present a more precise definition of local melanoma recurrence. Methods. A case is reported and the literature is reviewed. Conclusion. Owing to the myriad of different definitions that exist in the medical literature, the term “local melanoma recurrence” is ambiguous and at times misleading. Melanoma that recurs locally from persistence of tumor at the resection margins has a vastly different prognosis than recurrence developing from local (satellite) metastases adjacent to the surgical resection site. We propose the use of the terms “persistent melanoma” and “local metastasis” as more precise and predictive of a patient's prognosis.

Current robotic systems for minimally invasive surgery do not have effective means of providing haptics to the surgeon. It was hypothesized that providing an analog for force feedback through the visual channel could benefit performance in the absence of actual force feedback. An experiment was conducted to examine performance in a simple line-drawing task in a simulator box using a conventional laparoscopic grasper with inherent force feedback and a robotic manipulator with no force feedback. The task was performed on a hard surface and a soft surface. Physical deformation on the soft surface provided additional visual cues regarding the forces applied during the task. Results showed better performance, in the absence of force feedback, when the visual analog of force was provided. Task completion time was best when physical force feedback was combined with augmented visual feedback. This research has implications for the implementation of haptics in robotic surgical systems.

The American Joint Committee on Cancer has recently revised the staging system for melanoma. In this article, prognostic factors for melanoma are discussed in order of significance as outlined by the new staging system. In addition, other historically relevant prognostic factors are reviewed. The article concludes with a discussion of new technology, which may aid in the future staging of melanoma patients.

TPS1121 Background: Cutaneous metastases occur in approximately 20% of patients (pts) with metastatic breast cancer (mBC) and can be highly symptomatic and distressing. Radiation is frequently offered, but progression often occurs quickly. Photodynamic therapy is a promising approach with encouraging results in small studies. Here we will evaluate a novel Continuous Low-Irradiance Photodynamic Therapy (CLIPT) system that emits 690nm LED via a handheld powerpack attached to a single-use sterile light patch to deliver a total energy level of 10J/cm2. Verteporfin (Visudyne) is a photosensitizer approved for ophthalmological use that when combined with CLIPT generates activated oxygen species which can destroy tumor cells with limited normal tissue reaction. Methods: This open label, phase 2 study will evaluate the efficacy and safety of CLIPT with verteporfin in 15 pts with cutaneous lesions from mBC. Pts will receive a single IV injection of verteporfin on day 1. The 9x9cm patch with an adhesive border is placed over the treatment site and attached to the CLIPT portable power pack. The pt turns the device on at home 6 hours after the verteprofin injection and it automatically turns off after 24 hours. The pt will remove the patch and return to clinic on day 3. The primary endpoint is objective response rate (RR) at 3 weeks following CLIPT using a modified RECIST which accounts for nodular or diffuse plaque-like lesions. Secondary endpoints include RR at 2, 8 and 12 weeks, toxicity, and quality of life (using FACT-B, a Participant Symptom Scale, and Brief Pain Inventory). Pts who derive clinical benefit may be retreated up to 3 times to the same or different region. Eligible pts will have: cutaneous metastases from mBC with measurable disease by protocol defined modified RECIST 1.1, ≥ 1 line of prior systemic or local therapy for mBC, ≥ 14 days from prior systemic therapy or 60 days from radiation to target lesion, and no expectation for systemic therapy for ≥ 14 days after CLIPT. RR will be reported with 95% CI. If ≥ 3 responses (RR ≥ 20%) are observed, the null hypothesis of RR ≤ 5% will be rejected. At the time of abstract submission, 1 patient has been accrued. Clinical trial information: NCT02939274.

Superficial acral fibromyxoma is a rare, slow-growing soft tissue tumor, which is commonly located in the periungual and subungual regions of the fingers and toes in adults. To date, fewer than 50 cases have been reported worldwide. Microscopic examination reveals a moderately circumscribed, nonencapsulated tumor situated in the dermis, which may also extend into the subcutis. The neoplasm consists of a moderately cellular proliferation of stellate and spindle-shaped fibroblast-like cells embedded in a myxocollagenous stroma. Mast cells are easily identified throughout this lesion. Multinucleated stromal cells may also be present, but nuclear atypia and mitotic figures are rare. The tumor shows immunoreactivity for CD34, epithelial membrane antigen, CD99, and less frequently, CD10. Superficial acral fibromyxoma has a benign behavior but may persist or recur if inadequately excised. Therefore, complete excision and close follow-up are advised.

Background: Basal cell carcinoma (BCC) biopsy sites often heal with no clinical evidence of residual tumor. Objective: The purpose of our study is to determine whether such patients require further therapy. If biopsies can be curative, health care costs can be reduced by avoiding unnecessary surgery. Methods: We prospectively evaluated 41 consecutive subjects with 42 biopsy-confirmed BCCs who appeared disease free. Each biopsy site was excised and processed by the Mohs micrographic technique. The tissue block was sectioned horizontally at 30-μm intervals until exhausted. Sections were stained and examined microscopically for residual tumor. Results: Tumor was identified in 28 (66%) of 42 cases. No statistically significant relationship was found between the presence or absence of residual tumor and the following variables: age, sex, tumor location, biopsy technique, histopathologic subtype, scar size, time from biopsy to surgery, and extent of inflammation in histologic sections. Conclusion: Our data suggest that patients with small (

Background. Tissue-engineered products are usually composed of living cells and their supporting matrices that have been grown in vitro, using a combination of engineering and life sciences principles. Apligraf is a bilayered product composed of neonatal-derived dermal fibroblasts and keratinocytes, and Type I bovine collagen. Objective. To evaluate in a prospective, multicentered open study, the effects of tissue therapy with a tissue-engineered skin (Apligraf) with partial or full-thickness excisional wounds. Methods. One hundred and seven patients participated in this study. The tissue-engineered skin was applied once, immediately after excisional surgery, usually for skin cancer, and patients were followed for up to one year. Results. The safety results were impressive, with no clinical or laboratory evidence of rejection. Clinically, graft persistence was good to excellent in 77 of 105 (73.3%) of patients at one week, falling to 56.6% and 53.6% at two weeks and one month respectively. Conclusion. To date, this is the largest experience with a tissue-engineered skin product in acute wounds, and this study suggests that tissue therapy may be safe and useful.

After removal of skin lesions including carcinomas, surgery of the external ear repair provides a challenge to the surgeon anatomically and physiologically. The auricular cartilage has minimal vascularity and creates a convoluted physical conformation. Primary closures and grafts performed on surgical ear defects are difficult to design and execute. Fenestration of the auricular cartilage creates a rich vascular bed that aids in healing by secondary intention or graft uptake. The present article illustrates how to perform the above-mentioned surgical technique.

Background: Although the survival benefits of early stage melanoma have been clearly documented, the potential economic impact of early versus late stage disease has not been assessed. Objective: Our purpose was to estimate the annual direct cost of diagnosing and treating melanoma, based on the number of projected cases of melanoma entering each stage in 1997. Methods: A model was constructed with assumptions derived from the literature and clinical experience at the Massachusetts General Hospital Melanoma Center and the Boston University Medical Center. Cost estimates were based on 1997 Boston area Medicare reimbursements. Results: The annual direct cost of treating newly diagnosed melanoma in 1997 was estimated to be $563 million. Stage I and II disease each comprised about 5% of the total cost; stage III and stage IV disease consumed 34% and 55% of the total cost, respectively. About 90% of the total annual direct cost of treating melanoma in 1997 was attributable to less than 20% of patients (those patients with advanced disease, that is, stage III and stage IV). Conclusion: In addition to the potential survival advantages, aggressive primary prevention through sun protection and intensive screening to enhance earlier detection should reduce the economic burden of melanoma care.(J Am Acad Dermatol 1998;38:669-80.)

background. The term Marjolin ulcer is now synonymous with malignant transformation of chronic ulcers, sinus tracts, and burn scars. objective. To illustrate the importance of incisional or excisional biopsies in cases of suspected burn scar carcinoma. methods. Case report and review of the literature. results. Multiple punch biopsies were negative while a complete excision revealed the diagnosis of squamous cell carcinoma. conclusion. Because of the focal nature of malignant change in burn scars, incisional or excisional biopsy should be performed.

Background With the increasing number of patients with implantable cardiac devices, dermatologic surgeons must be increasingly familiar with the types of devices and potential interference by surgical procedures. Observations We report the excision of a 1 cm malignant melanoma in situ occurring on the skin directly overlying the patient's pacemaker. Conclusions Successful excision of malignant lesions in the setting of implantable cardiac devices requires an understanding of pacemaker implantation anatomy following well-established guidelines for electrosurgery in the setting of implantable cardiac devices and careful coordination with cardiac and anesthesia specialists. ANNE M. CHAPAS, MD, DENNIS LEE, MD, AND GARY S. ROGERS, MD, HAVE INDICATED NO SIGNIFICANT INTEREST WITH COMMERCIAL SUPPORTERS.

The use of medical adhesives for topical wound closure is gaining in popularity over conventional wound closure materials such as sutures and staples. Adhesives provide advantages in both wound closure and patient management with good cosmetic outcome and surgeon and patient satisfaction reported.To compare the use of two currently marketed medical adhesives; LiquiBand® Flow Control and High Viscosity Dermabond ™ for the topical closure of surgical incisions.In a prospective blinded manner, subjects were randomly assigned LiquiBand® or DermabondTM for topical closure of a surgical incision. Variables compared included ease of use, time taken to close wound, subject and surgeon satisfaction with device and wound closure, cosmetic outcome at 90 days, and complication rates.Use of both devices resulted in effective wound closure with similar high levels of cosmesis subject and surgeon satisfaction, with only minor complications reported. There was no statistically significant difference between the devices for all the parameters studied, with the exception that the Liquiband device was found to significantly reduce the amount of time required for closure.As the two devices appear substantially equivalent in terms of key surgeon and patient variables, product cost should be the primary determinant in selection of the tissue glue device.

To evaluate the effect of surgical excision, performed after biopsy diagnosis of dysplastic nevus, on final diagnosis, melanoma prevention, and melanoma detection.Outcome study using retrospective review conducted in an academic dermatopathology practice (Boston Medical Center Skin Pathology Laboratory) that receives specimens from community and academic practices across the United States. Consecutive patient pathology samples of dysplastic nevi and cutaneous melanomas evaluated between September 1, 1999 and March 1, 2011, and identified using systematized nomenclature of medicine codes were included.In dysplastic nevi cases, the rate of clinically significant change in diagnosis and the rate of melanoma detection as a result of excision. In melanoma cases, the rate and characteristics of association with dysplastic nevus.Of dysplastic nevi, 196 of 580 (34%) showed a positive biopsy margin, increasing with grade of atypia (P .001); 127 of 196 with positive biopsy margin received excision (65%), performed more often as grade of atypia increased (P .001). Two excisions (2 of 127, 1.6%) resulted in a clinically significant change in diagnosis, from biopsy-diagnosed moderately-to-severely dysplastic nevi before excision to melanoma in situ after excision. In melanomas (n = 216), in situ and superficial spreading subtypes were more often associated with dysplastic nevi (20% and 18%, respectively) (P = .002), most often of moderate-to-severe or severe grade.Excision of biopsy-diagnosed mildly or moderately dysplastic nevi is unlikely to result in a clinically significant change in diagnosis, and risk of transformation to melanoma appears very low. Moderately-to-severely and severely dysplastic nevi are more often associated with melanoma, and excision may be beneficial for melanoma detection or prevention.

background Because of the rising incidence of melanoma, dermatologists are increasingly responsible for diagnosing and managing patients with this cutaneous malignancy. Fortunately, with the increased awareness and emphasis on early detection, most patients will present with tumors that have not yet spread beyond their primary focus in the skin (ie, Stage I). Dermatologists must, therefore, be fully versed in the diagnosis and management of Stage I melanoma. objective This review article focuses on the most important issues related to the diagnosis and management of Stage I melanoma. An emphasis will be placed on surgical management. results The mainstay of therapy for most patients with Stage I melanoma is surgery. The important principles of diagnostic biopsy and surgical excision will be discussed. There are several additional modalities that may be useful as adjuvants to surgical therapy or as primary therapy in situations when surgery is not feasible. Those include elective lymph node dissection, hyperthermic isolation limb perfusion, radiotherapy, cryotherapy, chemotherapy, and immunotherapy. These will all be reviewed. conclusions With a thorough understanding of the important principles and controversies related to the management of Stage I melanoma, dermatologists can effectively manage the growing number of patients with this malignancy. learning objectives After studying the following article, participant should be able to: 1 Understand the proper diagnosis and evaluation of a patient with Stage I melanoma. 2 Understand the proper surgical management of Stage I melanoma. 3 Understand the available alternatives and adjuvants to surgical therapy of Stage I melanoma.

9509Background: VISMO, a first-in-class Hedgehog pathway inhibitor, is approved for use in adult pts with advanced BCC. Pts with multiple BCCs, including BCC nevus syndrome (BCCNS), require VISMO t...

A principal factor in determining the biologic consequences of photodynamic therapy (PDT) is the light fluence rate. Preclinical and, more recently, clinical studies have focused on low-irradiance schemes, suggesting that prolonged light exposure, better known as CLIPT (continuous low-irradiance PDT), may improve tumor control while reducing morbidity. After a brief look at the origin of light therapy and photosensitizers, this article turns to the promising animal research supporting the use of low- and ultra-low fluence rate PDT, which serves as the basis of the ongoing CLIPT dosimetry trials for patients with chest wall progression of breast cancer. The future of CLIPT seems to be a home-based therapy using a portable, self-contained energy delivery system.

Background Squamous cell carcinoma (SCC) in situ (SCCIS) is often treated without any pathologic confirmation of tumor clearance. It is unclear how often an invasive SCC is harbored within a lesion in which the initial biopsy demonstrated SCCIS because of inadequate sampling. This study examines the final histologic diagnosis of cases in which the initial biopsies were diagnosed as SCCIS and evaluates factors that may correlate with a histologic upstaging of the diagnosis. Methods We prospectively recruited 29 consecutive patients with biopsy-proven SCCIS sent for Mohs micrographic surgery (MMS). Each tumor underwent MMS, and the central blocks of the Mohs debulking specimens were horizontally sectioned at 30-μm intervals until exhausted. A fellowship-trained Mohs surgeon and a board-certified dermatopathologist processed and examined these sections to determine the final histologic diagnosis of the tumor. Results Of the 29 subjects with biopsy-proven SCCIS, nine were found to harbor invasive SCC on final histology. Of the remaining lesions, seven had residual SCCIS, whereas the rest exhibited only actinic keratoses or scars. Approximately 31% of lesions showed evidence of invasive SCC. Correlating the clinical characteristics of the lesions with their corresponding final histologic diagnoses, the lesions harboring invasive SCC were more likely to demonstrate clinical signs of residual tumor (scales and papular changes) and be larger than 1.4 cm in diameter. Limitations Our experience at a single institution in the northeastern United States may not be reflective of a wider population. There is also a possible referral bias, because only lesions with high clinical suspicion for invasive SCC were referred for MMS. Conclusion Although biopsy-proven SCCIS is often treated with modalities that are best suited for superficial disease and do not involve a final pathologic confirmation of clearance (e.g., cryotherapy, electrodesiccation and curettage), this study demonstrated that up to 31% of biopsy-proven SCCIS lesions may harbor invasive SCC. Clinical signs of residual tumor and a diameter larger than 1.4 cm are statistically significant predictors of underlying invasive SCC. These data suggest that treatment modalities that include histologic control of tumor removal should also be strongly considered for the treatment of select biopsy-proven SCCIS meeting the above criteria.

This study is the first double-blinded, randomized comparison of two absorbable sutures. To better understand product characteristics and surgeon preference, we conducted a study of two similar-appearing FDA-approved sutures, glyconate and poliglecaprone 25. Four dermatologic surgeons were enlisted. A total of 48 patients with 53 surgical sites were examined. One half of each surgical wound was closed with one type of suture and the other half with the other type. Each half was evaluated for product characteristics. There was no statistically significant difference in surgeon preference for glyconate versus poliglecaprone 25 (P=0.64). Of the cohort preferring poliglecaprone 25, there was a correlation with speed of closure (P=0.06). Of the surgeons that preferred glyconate, we found significantly better visibility (P=0.03), reduced suture breakage during knot tying (P=0.05), and correlation with better handling properties (P=0.06) associated with that preference. The data from this study will enable products to be designed towards these needs and allow surgeons to select sutures that more precisely fit their particular requirements.

Skin disorders are very common among elderly people. All physicians who care for this population should possess the ability to recognise common benign growths. Primary care physicians should also have the ability to recognise premalignant and malignant lesions, so that early diagnosis and treatment is possible. It is puzzling that the organ system most amenable to examination is so often overlooked in routine examinations. By simply taking the time to perform a skin examination, morbidity and mortality can be decreased. Through improvements in pharmacotherapy, particularly the development of more effective sunscreens, it may eventually be possible to markedly reduce the development of many benign and malignant skin lesions.

Background Melanoma is a life-threatening malignancy. Surgery is the primary management for melanoma, and management guidelines have evolved gradually over a century from radical surgery with lymph node dissection to conservative margin surgery. There are specific rationales and problems with Mohs micrographic (MMS) surgery for managing melanoma. Objective To review the literature for the surgical management of melanoma and to understand where MMS fits in this spectrum of management options. Conclusions MMS should be considered as an option for melanoma surgery, especially when the tumor is found in photodamaged skin. Further randomized prospective clinical trials are needed to select the best therapeutic approach for the treatment of melanoma. Until then, careful margin control is the key for successful tumor removal whether it is standard excision, staged excision, or MMS.

There is a general consensus that wounds heal more slowly in the elderly population and that all phases of the wound healing process are affected. Studies in both humans and animal models of wound healing suggest that aging is accompanied by decreased inflammatory and proliferative responses, delayed angiogenesis, delayed remodeling, and slower re-epithelialization. The available literature is compromised, however, by variable and sometimes inappropriate definitions of old age, lack of standardization for clinical wounds, incomplete descriptions of both methodology and results, and the frequent presence of confounding variables, especially in human studies. This article reviews the effects of age on wound healing and speculates on potential future therapies to enhance healing in older individuals.

BACKGROUND. Second primary melanoma is not a rare phenomenon. It occurs in at least 3 to 6% of melanoma patients and up to a third of individuals from melanoma-prone families. OBJECTIVE. To review the clinical and histologic features of multiple primary melanoma. A schema for follow-up of these patients is presented. CONCLUSIONS. As the incidence of melanoma continues to rise, we will be faced with an ever increasing number of patients who have survived their tumor. These patients are at risk for subsequent melanomas. This article reviews the literature regarding multiple primary melanoma, and discusses patient management.

Surgery for early cutaneous malignant melanoma has evolved over the past several decades towards more conservative management. Controversy regarding biopsy technique, appropriate margins for definitive resection, utility of lymph node dissection, and adjuvant therapies still abounds. This article explores the controversies and discusses current management strategies.

Perineural invasion (PNI) by cutaneous squamous cell carcinoma (CSCC) and basal cell carcinoma (BCC) is an infrequent but not rare complication of traditionally low-morbidity skin cancers that can lead to catastrophic sequelae; 2.5% to 14% of CSCC and approximately 3% of BCC exhibit PNI. Tumors with PNI tend to be larger, have greater subclinical extension, have a higher rate of recurrence, and have a greater risk of metastases. Tumors with PNI may result in major neurologic deficits.To review current recommendations for the management of PNI and to evaluate a treatment strategy involving excision using Mohs micrographic surgery (MMS) followed by adjunctive radiotherapy.Cases of PNI treated with MMS and radiotherapy were reviewed for recurrence, disease-free follow-up, and adverse events.Twelve patients with incidental PNI treated with MMS and adjunctive radiotherapy are presented. After 3 to 32 months of follow-up, there had been no recurrences. Adverse events from radiotherapy were minor and self-limited.The use of adjunctive radiotherapy in these patients remains controversial. When managing superficial skin tumors with PNI, a multidisciplinary team including a cutaneous surgeon and a radiation oncologist familiar with PNI is recommended.

Management of the aging face involves evaluation of the degree of solar elastosis, rhytidosis, and the structural changes associated with senescent skin. Chemical facial exfoliation is divided into deep, medium, and superficial based upon depth of penetration of the caustic agent used. Knowledge of the appropriate indications and technique are essential in obtaining optimal clinical results.

9022 Background: Advanced BCC (aBCC), including metastatic (mBCC) or locally advanced BCC (laBCC), is rare, and a broadly accepted diagnostic definition of aBCC is lacking. The RegiSONIC disease re...

9023 Background: Treatment of advanced BCC (aBCC), including metastatic or locally advanced (la) BCC, is challenging, with approaches ranging from surgery to recently approved targeted Hedgehog pat...

Background:Actinickeratoses(AKs)aredysplasticepidermal lesions considered to be potential precursors of squamous cell carcinoma. Most AKs are diagnosed clinically and are rarely confirmed histologically. High interobservervariationexistsamongdermatologistsforthe diagnosis of AKs. Previous studies of the positive predictive value of the diagnosis of AKs have yielded rates as high as 94%. This study evaluates the rate at which histologicanalysisconfirmstheclinicalimpression(positive predictive value) of AKs in patients with a history of skin cancer. Observations:Seventeen(74%)of23lesionswithclassic features of AKs, as determined by 3 dermatologists, were confirmed as AKs histologically. These were lesionsthatwouldordinarilynotbebiopsied.Ofthe6misdiagnoses, 5 (83%) were skin cancer, most often squamous cell carcinoma. Conclusions: The positive predictive value of 74% for the diagnosis of AKs in this study is substantially lower than that of 2 previous studies, suggesting that physicians may be misdiagnosing many patients with classic features of AKs. Most misdiagnosed cases were forms of skin cancer. These preliminary data suggest that the threshold for biopsy of suspect lesions in patients with a history of skin cancer should be low and warrant further evaluation. Arch Dermatol. 2005;141:507-509

Success in robotic minimally invasive surgery (MIS) has been limited despite the innovations in robotic technology for surgical applications. Human factors engineering approach to the design and implementation of this technology is major to improving system performance and patient safety. The engineering discipline of human factors involves the study of factors and development of tools that enable human interaction with systems in a safe and effective manner. Human factors contribution is important to the product design life cycle, as it supports the design of a product capable of supporting, extending, and transforming user work in a cost-effective and timely fashion. A framework for modelling the interaction between the surgeon and technology in MIS is presented. This approach allows for identification of requirements and constraints at the physical, functional, and cognitive levels, which in turn guides the design of the technology and its interface. The human factors approach is expected to increase the effectiveness of the technology when deployed.

TPS9121 Background: Vismodegib, a Hedgehog signaling pathway inhibitor, is FDA and EMA approved for patients (pts) with advanced basal cell carcinoma (BCC) who are not candidates for surgery or rad...

background. Botulinum A exotoxin injection is a well-established method for treatment of glabellar frown lines, crow's feet, and horizontal furrows of the forehead. However, there is no consensus as to the optimal dosage per injection site or the concentration of injectate to be used. objective. The purpose of this study was to determine the minimal effective dose per injection site to be used as well as the effect of concentration in response to treatment. results. A total of 46 subjects were divided into ten groups and injected with escalating doses and concentrations of botulinum toxin. The response and longevity of treatment were then followed on a monthly basis. A dose between 2.5–4 U per injection site (12.5–20 U total) was determined to be an effective starting dose, with a duration of 2–5 months (median 14 weeks). conclusions. There was no statistically significant difference in safety or efficacy for concentrations ranging from 50 to 200 U/ml of botulinum toxin.

Background: The use of cutaneous resurfacing lasers to treat rhytides is widely accepted. Several carbon dioxide lasers, many using fundamentally different technologies, are available. Objective: The purpose of this study was to compare the results obtained and side effects after treating rhytides with 3 different carbon dioxide resurfacing lasers. Methods: We performed a randomized, blinded, prospective study wherein 16 subjects had either periorbital or perioral rhytides resurfaced with 1 of 3 carbon dioxide lasers on either side of the face. Results: We were unable to demonstrate any significant differences in improvement in rhytides, patient satisfaction, posttreatment erythema, or other side effects. Conclusion: Our results suggest that operator technique and patient selection are more important factors than laser type with respect to outcome. (J Am Acad Dermatol 1998;39:547-53.)

Malignant melanoma is associated with an excellent long-term prognosis when detected and treated at an early stage. Surgery alone is sufficient for patients with thin melanomas. Patients with thicker tumors, who are at higher risk for metastasis, may benefit from additional therapy beyond surgical removal of the tumor. Adjuvant therapies are designed to reduce the risk of melanoma recurrence. In particular, the immunotherapies, which boost the host's immune response to the cancer, are proving to be valuable adjuncts to surgery. Once melanoma has metastasized to a visceral organ, the prognosis is poor. Metastatic melanoma has a poor response to most conventional treatments. Boron neutron capture therapy is a novel approach to cancer management. It is a binary therapy combining low energy, nonionizing neutron irradiation with a stable isotope of naturally occurring boron avidly absorbed by the tumor. The combined approach currently under investigation results in highly selective tumor destruction.