Faculty Bibliography

There is controversy regarding the optimal surgical modality and ideal recommended margins for treating melanoma in situ (MIS) and invasive melanoma (IM). Although wide local excision is recommended, staged excision offers excellent margin control and low recurrence rates. In this manuscript, we reviewed a 10-year experience of staged excisions for the treatment of MIS and IM. A retrospective review was performed of 130 MIS and 32 IM cases treated with staged excision from April 2012 to April 2022. Staged excision was performed on the head and neck in 102 (79%) MIS and 23 (72%) IM cases. Approximately 10% of cases required surgical margins above the current recommendations (11 (9%) MIS and 6 (19%) IM). Twenty-three (19%) MIS and 7 (22%) IM cases required more than one excision to obtain clearance. Recurrence rates among MIS and IM were 0.0% and 0.6%, respectively. Upstaging occurred in 5 (4%) MIS and 7 (22%) IM cases. Complex repairs were performed on 82 (63%) MIS and 17 (53%) IM cases. Our findings revealed that staged excision provides effective margin control and low recurrence rates. Approximately 10% of patients required margins greater than the current recommendations, leading to larger defects and more complex repairs.

INTRODUCTION/BACKGROUND:Nasal reconstruction has important functional and cosmetic considerations, as proper repair of nasal defects is necessary to maintain function of the nasal airway and to recreate the normal appearance of this central facial structure. Cheek advancement flaps provide matched, mobile and highly vascularized tissue for the reconstruction of nasal defects, allowing for the concealment of incisions within natural creases in a one-stage approach. However, cheek advancement flaps are often underutilized for nasal reconstruction because of their difficulty restoring nasal contour. METHODS:We describe reconstruction of 19 nasal dorsal and sidewall defects 0.8 to 3.0 centimeters (cm) in size. We incorporated a periosteal anchoring suture to maintain/restore nasal contour and additionally removed a half standing cone inferior to the defect to prevent encroachment of the nasal ala or alar crease. All patients were evaluated at least 3 months post-operatively. RESULTS:In all patients, we were able to restore concavity of the nasofacial sulcus, preserve the biconvex nasal tips, prevent alar flaring and retraction and conserve the alar groove. All patients had excellent functional and cosmetic outcomes. CONCLUSION/CONCLUSIONS:We believe this modified cheek advancement flap provides functionally and aesthetically superior results and can be considered as a first-line approach for repair of nasal dorsal and sidewall defects in sub selected patients.

LINE-1 retrotransposons are sequences capable of copying themselves to new genomic loci via an RNA intermediate. New studies implicate LINE-1 in a range of diseases, especially in the context of aging, but without an accurate understanding of where and when LINE-1 is expressed, a full accounting of its role in health and disease is not possible. We therefore developed a method-5' scL1seq-that makes use of a widely available library preparation method (10x Genomics 5' single cell RNA-seq) to measure LINE-1 expression in tens of thousands of single cells. We recapitulated the known pattern of LINE-1 expression in tumors-present in cancer cells, absent from immune cells-and identified hitherto undescribed LINE-1 expression in human epithelial cells and mouse hippocampal neurons. In both cases, we saw a modest increase with age, supporting recent research connecting LINE-1 to age related diseases.

IMPORTANCE/UNASSIGNED:Primary cutaneous squamous cell carcinoma is usually curable; however, a subset of patients develops poor outcomes, including local recurrence, nodal metastasis, distant metastasis, and disease-specific death. OBJECTIVES/UNASSIGNED:To evaluate all evidence-based reports of patient risk factors and tumor characteristics associated with poor outcomes in primary cutaneous squamous cell carcinoma and to identify treatment modalities that minimize poor outcomes. DATA SOURCES/UNASSIGNED:PubMed, Embase, and SCOPUS databases were searched for studies of the topic in humans, published in the English language, from database inception through February 8, 2022. STUDY SELECTION/UNASSIGNED:Two authors independently screened the identified articles and included those that were original research with a sample size of 10 patients or more and that assessed risk factors and/or treatment modalities associated with poor outcomes among patients with primary cutaneous squamous cell carcinoma. DATA EXTRACTION AND SYNTHESIS/UNASSIGNED:Data extraction was performed by a single author, per international guidelines. The search terms, study objectives, and protocol methods were defined before study initiation. A total of 310 studies were included for full-text assessment. Owing to heterogeneity of the included studies, a random-effects model was used. Data analyses were performed from May 25 to September 15, 2022. MAIN OUTCOMES AND MEASURES/UNASSIGNED:For studies of risk factors, risk ratios and incidence proportions; and for treatment studies, incidence proportions. RESULTS/UNASSIGNED:In all, 129 studies and a total of 137 449 patients with primary cutaneous squamous cell carcinoma and 126 553 tumors were included in the meta-analysis. Several patient risk factors and tumor characteristics were associated with local recurrence, nodal metastasis, distant metastasis, disease-specific death, and all-cause death were identified. Among all factors reported by more than 1 study, the highest risks for local recurrence and disease-specific death were associated with tumor invasion beyond subcutaneous fat (risk ratio, 9.1 [95% CI, 2.8-29.2] and 10.4 [95% CI, 3.0- 36.3], respectively), and the highest risk of any metastasis was associated with perineural invasion (risk ratio, 5.0; 95% CI, 2.3-11.1). Patients who received Mohs micrographic surgery had the lowest incidence of nearly all poor outcomes; however, in some results, the 95% CIs overlapped with those of other treatment modalities. CONCLUSIONS AND RELEVANCE/UNASSIGNED:This meta-analysis identified the prognostic value of several risk factors and the effectiveness of the available treatment modalities. These findings carry important implications for the prognostication, workup, treatment, and follow-up of patients with primary cutaneous squamous cell carcinoma. TRIAL REGISTRATION/UNASSIGNED:PROSPERO Identifier: CRD42022311250.

Primary cutaneous squamous cell carcinoma (cSCC) is the second most common human cancer with a rising incidence of about 1.8 million in the United States annually. Primary cSCC is usually curable by surgery; however, in some cases, cSCC eventuates in nodal metastasis and death from disease specific death. cSCC results in up to 15,000 deaths each year in the United States. Until recently, non-surgical options for treatment of locally advanced or metastatic cSCC were largely ineffective. With the advent of checkpoint inhibitor immunotherapy, including cemiplimab and pembrolizumab, response rates climbed to 50%, representing a vast improvement over chemotherapeutic agents used previously. Herein, we discuss the phenotype and function of SCC associated Langerhans cells, dendritic cells, macrophages, myeloid derived suppressor cells and T cells as well as SCC-associated lymphatics and blood vessels. Possible role(s) of SCC-associated cytokines in progression and invasion are reviewed. We also discuss the SCC immune microenvironment in the context of currently available and pipeline therapeutics.

Deliberate practice-based medical education has demonstrated superiority in trainee acquisition and maintenance of skills in several surgical subspecialties. In an effort to highlight the impact of a deliberate practice-based surgical curriculum on the technical proficiency of dermatology residents, a prospective cohort study including first- and second-year dermatology residents was performed. A total of 87.5% (7 of 8) first-year dermatology residents completed three hands-on simulations at 6-week intervals. Additionally, six of eight (75.0%) second-year dermatology residents at the same institution were evaluated at a single point-in-time session without accessing the surgical curriculum prior. A 5-point global rating scale (GRS) was used to assess resident performance on six core surgical techniques. Nonparametric ANOVA statistical methods using the Kruskal-Wallis test was performed. The residents' overall GRS increased from a median of 1-2.75 after completion of the curriculum (p < 0.01). There was a significant improvement in the median scores of each tested surgical technique. The first-year residents had a greater overall GRS after completion of the curriculum compared to the second-year residents (median of 2.13 versus 1.88, p < 0.001). Limitations include the small sample size and lack of a synchronized control group. Our study highlights the use of deliberate practice-based strategies as an effective modality in teaching surgical skills to dermatology residents.