Faculty Bibliography

The utility of laser therapy is increasingly being recognized in the treatment of active acne vulgaris. We aimed to perform a narrative review of the medical literature on the use of laser therapy for the treatment of active acne vulgaris. We performed a PubMed literature search on September 1, 2016 using the search terms "active acne," "acne," "laser therapy," and "laser surgery." Case reports, case series, cohort, and controlled trials were included. Studies of lasers in the treatment of acne, including erbium glass, Nd:YAG, pulse dye laser (PDL), potassium titanyl phosphate (KTP) laser, and laser-based photodynamic therapy, have been published. While treatment of active acne with lasers has been successful, many studies are limited by small patient number and lack of control populations and comparison to standard therapies for active acne. Laser therapies are increasingly becoming part of or an adjunct to the medical treatment of active acne and are a useful treatment modality.

For rapid pathological assessment of large surgical tissue excisions with cellular resolution, we present a line scanning, stage scanning confocal microscope (LSSSCM). LSSSCM uses no scanning mirrors. Laser light is focused with a single cylindrical lens to a line of diffraction-limited width directly into the (Z) sample focal plane, which is parallel to and near the flattened specimen surface. Semi-confocal optical sections are derived from the linear array distribution (Y) and a single mechanical drive that moves the sample parallel to the focal plane and perpendicular to the focused line (X). LSSSCM demonstrates cellular resolution in the conditions of high nuclear density within micronodular basal cell carcinoma.

Photodynamic therapy (PDT) uses a topical photosensitizing agent which is activated by a light source to cause destruction of specific cells. Commonly used for the treatment of actinic keratoses and photodamage, PDT can also be used for other conditions including acne and sebaceous hyperplasia. Here we report our experience with two treatment protocols. The first protocol utilizes laser assisted delivery of topical 5-aminolevulinic acid for enhanced efficacy of blue light photodynamic therapy in the treatment of actinic keratoses and photodamage. The second protocol utilizes red light photodynamic therapy followed by pulsed dye laser to effectively target sebaceous glands in patients with extensive sebaceous hyperplasia

J Drugs Dermatol. 2017;16(4):329-331

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Importance: Limited therapies are available in patients with inoperable locally advanced cutaneous squamous cell carcinoma (cSCC). Objective: To determine the efficacy of programmed cell death 1 receptor (PD-1) inhibitors in locally advanced cSCC. Design, Setting, and Participants: A single patient with locally advanced cSCC who declined surgery and radiotherapy underwent treatment with pembrolizumab, an anti-PD-1 antibody, at an academic dermatologic surgery section and cancer center. The patient was followed up for clinical and radiologic regression of cSCC. With the use of NanoString to amplify potential biomarkers, immunohistochemistry, and immunofluorescence, the ex vivo expression of PD-1 and a ligand (PD-L2) was assessed in 38 cSCC biopsy specimens from 24 patients with cSCC. Expression of PD-L1 and PD-L2 in the cSCC microenvironment was defined. Intervention: Pembrolizumab, 2 mg/kg every 3 weeks, for 4 cycles. Main Outcomes and Measures: Expression of PD-L1 and PD-L2 in the cSCC microenvironment. Results: In 1 patient with locally advanced cSCC who was treated with pembrolizumab, nearly complete tumor regression was observed after 4 cycles of therapy. The NanoString technology used in 38 cSCC biopsy specimens from 24 patients with cSCC (19 men and 5 women; mean [SD] age, 76.4 [12.2] years) detected increased PD-1 and PD-L2 expression in high-risk cSCC. Immunohistochemical analysis confirmed enhanced expression of PD-1 and its ligands in cSCC with perineural invasion (mean [SEM] expression, 5.06 [1.27]; P = .05), superficial cSCC (mean [SEM] expression, 3.58 [1.50]; P = .15), organ transplant-associated cSCC (mean [SEM] expression, 3.01 [0.54]; P = .005), and infiltrative cSCC (mean [SD] expression, 2.01 [0.30]; P = .006) compared with normal skin specimens. In double-label immunofluorescence staining, CD11c+, a marker of myeloid dendritic cells, colocalized with PD-L1 and PD-L2 in cSCC lesions. Conclusions and Relevance: The favorable treatment response combined with significant involvement of PD-1 and PD ligands in cSCC lesions suggests that PD-1 blockade may be a viable therapeutic option for locally advanced cSCC and provides rationale for further investigation in future clinical trials.

Importance: Confocal microscopy has the potential to provide rapid bedside pathologic analysis, but clinical adoption has been limited in part by the need for physician retraining to interpret grayscale images. Digitally stained confocal mosaics (DSCMs) mimic the colors of routine histologic specimens and may increase adaptability of this technology. Objective: To evaluate the accuracy and precision of 3 physicians using DSCMs before and after training to detect basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) in Mohs micrographic surgery fresh-tissue specimens. Design: This retrospective study used 133 DSCMs from 64 Mohs tissue excisions, which included clear margins, residual BCC, or residual SCC. Discarded tissue from Mohs surgical excisions from the dermatologic surgery units at Memorial Sloan Kettering Cancer Center and Oregon Health & Science University were collected for confocal imaging from 2006 to 2011. Final data analysis and interpretation took place between 2014 and 2016. Two Mohs surgeons and a Mohs fellow, who were blinded to the correlating gold standard frozen section diagnoses, independently reviewed the DSCMs for residual nonmelanoma skin cancer (NMSC) before and after a brief training session (about 5 minutes). The 2 assessments were separated by a 6-month washout period. Main Outcomes and Measures: Diagnostic accuracy was characterized by sensitivity and specificity of detecting NMSC using DSCMs vs standard frozen histopathologic specimens. The diagnostic precision was calculated based on interobserver agreement and kappa scores. Paired 2-sample t tests were used for comparative means analyses before and after training. Results: The average respective sensitivities and specificities of detecting NMSC were 90% (95% CI, 89%-91%) and 79% (95% CI, 52%-100%) before training and 99% (95% CI, 99%-99%) (P = .001) and 93% (95% CI, 90%-96%) (P = .18) after training; for BCC, they were 83% (95% CI, 59%-100%) and 92% (95% CI, 81%-100%) before training and 98% (95% CI, 98%-98%) (P = .18) and 97% (95% CI, 95%-100%) (P = .15) after training; for SCC, they were 73% (95% CI, 65%-81%) and 89% (95% CI, 72%-100%) before training and 100% (P = .004) and 98% (95% CI, 95%-100%) (P = .21) after training. The pretraining interobserver agreement was 72% (kappa = 0.58), and the posttraining interobserver agreement was 98% (kappa = 0.97) (P = .04). Conclusions and Relevance: Diagnostic use of DSCMs shows promising correlation to frozen histologic analysis, but image quality was affected by variations in image contrast and mosaic-stitching artifact. With training, physicians were able to read DSCMs with significantly improved accuracy and precision to detect NMSC.

BACKGROUND: While infrequent, nodal metastases in cutaneous squamous cell carcinoma (cSCC) can result in death from disease. Identification of those at risk for metastases is key to improved prognostication and treatment. OBJECTIVE: To review metastatic cSCC at the study institution. METHODS AND MATERIALS: Sixteen patients with metastatic cSCC were identified at the New York University Dermatologic Associates and Cancer Associates from 1998 to 2013. Patients were staged with American Joint Committee on Cancer (AJCC) and modified Brigham and Women's Hospital (BWH) criteria and compared to 32 control subjects. RESULTS: Seven of 16 patients were identified as Stage T2 by AJCC criteria and Stage T2b by BWH criteria; two patients were on Stage T1, three patients were on more advanced T stages, and four patients lacked primary tumor data. Five patients had hematologic malignancy, and one patient had a solid-organ transplant. CONCLUSION: The modified BWH criteria aims to better prognosticate the large group of T2 AJCC tumors, resulting in the majority of mortality. In the experience of the authors, the majority of patients with metastatic disease were on T2, stratifying to stage T2b by BWH criteria, or more advanced T stages. The findings of this study support BWH stratification of T2 tumors and also indicate that hematologic malignancy is a significant comorbidity associated with a poor outcome.

We created a line-scanning, stage scanning confocal microscope as part of a new procedure: video assisted micrographic surgery (VAMS). The need for rapid pathological assessment of the tissue on the surface of skin excisions very large since there are 3.5 million new skin cancers diagnosed annually in the United States. The new design presented here is a confocal microscope without any scanning optics. Instead, a line is focused in space and the sample, which is flattened, is physically translated such that the line scans across its face in a direction perpendicular to the line its self. The line is 6mm long and the stage is capable of scanning 50 mm, hence the field of view is quite large. The theoretical diffraction-limited resolution is 0.7um lateral and 3.7um axial. However, in this preliminary report, we present initial results that are a factor of 5-7 poorer in resolution. The results are encouraging because they demonstrate that the linear array detector measures sufficient signal from fluorescently labeled tissue and also demonstrate the large field of view achievable with VAMS.

OBJECTIVE: The purpose of this study was to analyze the efficacy and safety of the 585nm pulsed dye laser for the treatment of idiopathic flushing with dysesthesia. DESIGN: This was a retrospective study of patients treated with a 585nm pulsed dye laser with fluences ranging from 3.5 to 7.5J/cm(2) (purpura threshold fluences), a pulse duration of 450musec, and a spot size of 5 or 10mm. SETTING: The Ronald 0. Perelman Department of Dermatology at New York University Medical Center. PARTICIPANTS: Ten adult subjects who presented with flushing with dysesthesia. MEASUREMENTS: PARTICIPANTS subjectively evaluated the decrease in dysesthesia and the number of flushing episodes. The objective response to treatment was evaluated by a single physician using pre- and postoperative photographs. The severity of postoperative erythema was compared with baseline using an ordinal scale ranging from zero (resolution of erythema) to four (76-100% of baseline erythema). RESULTS: The mean number of treatments received by the subjects was seven. The mean fluence was 6.66J/cm(2). Subjectively, 100 percent of subjects reported a decrease in dysethesia and the number of flushing episodes. OBJECTIVEly, subjects demonstrated at least a 62.5-percent reduction in erythema. CONCLUSION: Laser surgery provided subjective relief of dysesthesia and decreased the number of flushing episodes with a greater than 62-percent objective reduction in the severity of erythema. The 585nm pulsed dye laser is a safe, efficacious treatment for the signs and symptoms of idiopathic flushing with dysesthesia.