CAPABLE: A Scoring System Utilizing Patient-Reported Measures to Evaluate Patient Experience After Mohs Surgery.

BACKGROUND: Patient experience metrics are gaining prominence in health care. We introduce the CAPABLE survey to assess postoperative experiences of Mohs surgery patients. OBJECTIVE: We sought to determine whether CAPABLE scores aligned with overall patient satisfaction in Mohs surgery. METHODS: This was a cross-sectional, survey-based study of patients presenting for their first postoperative visit after Mohs surgery. The CAPABLE survey included questions on postoperative instructions, activity limitations, pain control, provider accessibility, and bleeding, followed by 2 overall satisfaction questions taken from the Outpatient and Ambulatory Surgery Consumer Assessment of Healthcare Providers and Systems survey. The pilot study took place at the University of Texas Dell Medical School (DMS), followed by a validation study ( n = 206) at DMS and Oregon Health and Science University (OHSU). We assessed for correlations between CAPABLE scores and overall satisfaction. RESULTS: In the pilot study ( n = 137), overall CAPABLE scores and scores of individual CAPABLE components correlated positively with overall satisfaction.In the multisite validation study ( n = 206) spanning DMS and OHSU, CAPABLE scores correlated positively with overall satisfaction. CONCLUSION: The CAPABLE survey is a concise tool for assessing specific, actionable components of the postoperative patient experience in Mohs surgery, while correlating with overall patient satisfaction.

Multimodal Analysis of Composition and Spatial Architecture in Human Squamous Cell Carcinoma.

To define the cellular composition and architecture of cutaneous squamous cell carcinoma (cSCC), we combined single-cell RNA sequencing with spatial transcriptomics and multiplexed ion beam imaging from a series of human cSCCs and matched normal skin. cSCC exhibited four tumor subpopulations, three recapitulating normal epidermal states, and a tumor-specific keratinocyte (TSK) population unique to cancer, which localized to a fibrovascular niche. Integration of single-cell and spatial data mapped ligand-receptor networks to specific cell types, revealing TSK cells as a hub for intercellular communication. Multiple features of potential immunosuppression were observed, including T regulatory cell (Treg) co-localization with CD8 T cells in compartmentalized tumor stroma. Finally, single-cell characterization of human tumor xenografts and in vivo CRISPR screens identified essential roles for specific tumor subpopulation-enriched gene networks in tumorigenesis. These data define cSCC tumor and stromal cell subpopulations, the spatial niches where they interact, and the communicating gene networks that they engage in cancer.

Atypical Fibroxanthoma and Pleomorphic Dermal Sarcoma: Updates on Classification and Management.

Atypical fibroxanthoma and undifferentiated pleomorphic sarcoma, or pleomorphic dermal sarcoma, are rare malignant cutaneous neoplasms existing along a clinicopathologic spectrum. Although these tumors share many similarities, recognition of distinguishing characteristics may predict differences in clinical behavior and outcomes. Salient features defining atypical fibroxanthoma include superficial tumors with minimal high-risk histologic features. Deeper tumors with high-risk histologic features are often clinically aggressive and should be appropriately designated as pleomorphic dermal sarcoma. Surgery remains gold standard in management; tumor extirpation with complete margin control is critical. In the high-risk tumor cohort, comprehensive evaluation and multidisciplinary management is paramount for optimal outcomes.

PD-L1 Expression and Tumor-Infiltrating Lymphocytes in High-Risk and Metastatic Cutaneous Squamous Cell Carcinoma.

OBJECTIVE: To characterize programmed death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocyte (TIL) positivity for locally aggressive or regionally metastatic cutaneous head and neck squamous cell carcinoma (cHNSCC). STUDY DESIGN: Retrospective chart review, followed by immunohistochemical staining of archived tumor specimens. SETTING: Tertiary academic medical center. SUBJECTS AND METHODS: After identification of 101 patients treated surgically for locally advanced or regionally metastatic cHNSCC, archived tissue was stained and graded for PD-L1 expression in addition to TIL presence. Cross-tabulation was performed to examine the association between either of these variables and clinicopathologic features and outcomes. RESULTS: A total of 101 patients met inclusion criteria, but archived tissue was available only for 83 (31 primaries, 52 metastases). The majority of primary tumors demonstrated grade 1 PD-L1 staining, while grade 2 staining was more likely for metastases. Neither high- nor low-grade PD-L1 expression correlated with any clinicopathologic variable for primary tumors. However, for metastases, high-grade staining was significantly associated with regional recurrence (15 of 19, P = .02). TILs were present for 65% of primary tumors and 90% of regional metastases but did not correlate with any clinicopathologic variables. CONCLUSION: Diffuse expression of PD-L1 in this study highlights the possibility of using immunotherapy in the form of programmed death 1/PD-L1 blockade to improve treatment for this devastating disease. However, further studies are needed to clarify the significance of PD-L1 expression and TIL positivity for locally advanced or regionally metastatic cHNSCC.

Clinical perineural invasion of cutaneous head and neck cancer: Impact of radiotherapy, imaging, and nerve growth factor receptors on symptom control and prognosis.

OBJECTIVES: Clinical perineural invasion (CPNI) of cutaneous head and neck cancer is associated with poor prognosis and presents a therapeutic dilemma. The purpose of this study was to determine the relationship between CPNI and nerve growth factor receptors (NGFR), and the impact of radiotherapy (RT), imaging, and NGFR on symptom control and disease-related outcomes. MATERIALS AND METHODS: We retrospectively reviewed patients with CPNI of cutaneous head and neck cancer who were treated with RT between 2010 and 2015 at our institution. Exact chi-square and Wilcoxon rank-sum tests compared patients with positive versus negative staining for TrkA and/or CD271. Gray's test determined differences in cumulative incidences of 1- and 2-year locoregional recurrence (LRR) and cancer-specific mortality (CSM). RESULTS: Twenty-three patients had a median overall follow-up of 31.4 months from initial clinical symptoms and 19.7 months from pathological confirmation of PNI. The most prevalent symptoms were numbness (70%) and pain (57%). Sixteen patients (70%) experienced symptom improvement or control, especially decreased pain (85%), within a median of 2.6 months from starting RT. The 1- and 2-year rates of overall LRR were 37% and 71%, while those of overall CSM were 11% and 25%, respectively. Patients who stained positively for TrkA and/or CD271 had significantly worse LRR compared to patients who stained negatively for both markers (p = 0.046). CONCLUSION: Positive TrkA and/or CD271 staining predicts worse outcomes. Patients may benefit from aggressive RT for local control and symptom improvement. Future research is needed to identify the potential for anti-nerve growth factor therapies in CPNI.

Noncanonical hedgehog pathway activation through SRF-MKL1 promotes drug resistance in basal cell carcinomas.

Hedgehog pathway-dependent cancers can escape Smoothened (SMO) inhibition through mutations in genes encoding canonical hedgehog pathway components; however, around 50% of drug-resistant basal cell carcinomas (BCCs) lack additional variants of these genes. Here we use multidimensional genomics analysis of human and mouse drug-resistant BCCs to identify a noncanonical hedgehog activation pathway driven by the transcription factor serum response factor (SRF). Active SRF along with its coactivator megakaryoblastic leukemia 1 (MKL1) binds DNA near hedgehog target genes and forms a previously unknown protein complex with the hedgehog transcription factor glioma-associated oncogene family zinc finger-1 (GLI1), causing amplification of GLI1 transcriptional activity. We show that cytoskeletal activation through Rho and the formin family member Diaphanous (mDia) is required for SRF-MKL-driven GLI1 activation and for tumor cell viability. Remarkably, nuclear MKL1 staining served as a biomarker in tumors from mice and human subjects to predict tumor responsiveness to MKL inhibitors, highlighting the therapeutic potential of targeting this pathway. Thus, our study illuminates, for the first time, cytoskeletal-activation-driven transcription as a personalized therapeutic target for combatting drug-resistant malignancies.

The superiorly based bilobed flap for nasal reconstruction.

BACKGROUND: The laterally based bilobed flap is commonly used for the reconstruction of small- to medium-sized defects of the distal portion of the nose; However, when this flap is used to repair defects that are larger, more cephalic, or more lateral on the nose, there is a risk for lower nasal distortion. Reorienting the base superiorly preserves the advantages of the traditional design while minimizing this risk. OBJECTIVE: To demonstrate the design, execution, and efficacy of the superiorly based bilobed flap. METHODS: A retrospective review examined all superiorly based bilobed flaps performed by 1 surgeon (J.C.) in 2000-2016 after tumor extirpation by Mohs micrographic surgery at a single institution. RESULTS: A total of 41 surgical defects were closed with 40 flaps between June 2000 and August 2016 (1 patient had 2 defects closed with a single flap). Of the tumors, 55% were located on the nasal dorsum, and the median of the longest postoperative tumor axis was 1.4 cm. Follow-up was available for 40 flaps, and no infections, hematomas, or episodes of full-thickness necrosis were observed. LIMITATIONS: Data were collected retrospectively from a single institution without a standardized assessment tool for aesthetic outcomes. CONCLUSION: The superiorly based bilobed flap is useful for nasal reconstruction.

The Nasal Tip Rotation Flap for Reconstruction of the Lateral Nasal Tip, Anterior Ala, and Soft Triangle: The Authors' Experience With 55 Patients.

BACKGROUND: Defects of the lateral nasal tip, anterior ala, and soft triangle subunits lack reconstructive options that are consistently satisfactory. For such defects, the novel anterior-based nasal tip rotation flap provides functional and aesthetic results in a single operative session. OBJECTIVE: To describe the authors' experience with the nasal tip rotation flap, including patient selection and design modifications to enhance aesthetic success. METHODS: An IRB-approved retrospective database review of nasal tip rotation flap repairs was performed at the Medical University of South Carolina and Stanford University Medical Center. The design and surgical technique of this flap are described and illustrated, emphasizing factors such as nasal shape and defect location in modifying flap design. RESULTS: The nasal tip rotation is a single-stage, local flap that provides optimal tissue match with recapitulation of the native topography of the nasal tip and incision lines that are well hidden at the junction of cosmetic subunits. The mechanics of the flap distribute closure tension widely across the alar rim without focal notching or airway compromise. CONCLUSION: The nasal tip rotation flap is a reliable, cosmetically elegant repair that fills a gap in the reconstructive options for anterior ala and soft triangle defects on the nose.

Management of High-Risk Squamous Cell Carcinoma of the Skin.

OPINION STATEMENT: Non-melanoma skin cancer (NMSC) is the most common malignancy in the USA, with cutaneous squamous cell carcinomas (cSCCs) constituting approximately 20 % of all NMSC. While cSCCs typically behave in an indolent fashion and can be cured with local destructive or surgical methods, a small subset metastasizes and induces significant morbidity and mortality. Identifying and aggressively treating these "high-risk" cSCCs (HRcSCCs) is thus paramount. Recent improvements in staging cSCCs appear to offer better risk stratification than earlier staging criteria. Radiologic imaging and sentinel lymph node biopsy may be beneficial in certain cases of HRcSCC, although more studies are needed before these techniques should be uniformly incorporated into management. Surgery with complete margin control, such as that offered by the Mohs micrographic technique, represents the first-line treatment for these tumors. Radiation therapy is likely most beneficial in the adjuvant setting. Chemotherapy is typically best reserved for patients with metastatic or locally advance disease that is not controllable with surgical and/or radiation therapies. Newer targeted treatments, such as EGFR inhibitors and immunotherapies may offer greater efficacy in these settings, although further evaluation is needed.

CALML5 is a ZNF750- and TINCR-induced protein that binds stratifin to regulate epidermal differentiation.

Outward migration of epidermal progenitors occurs with induction of hundreds of differentiation genes, but the identities of all regulators required for this process are unknown. We used laser capture microdissection followed by RNA sequencing to identify calmodulin-like 5 (CALML5) as the most enriched gene in differentiating outer epidermis. CALML5 mRNA was up-regulated by the ZNF750 transcription factor and then stabilized by the long noncoding RNA TINCR. CALML5 knockout impaired differentiation, abolished keratohyalin granules, and disrupted epidermal barrier function. Mass spectrometry identified SFN (stratifin/14-3-3σ) as a CALML5-binding protein. CALML5 interacts with SFN in suprabasal epidermis, cocontrols 13% of late differentiation genes, and modulates interaction of SFN to some of its binding partners. A ZNF750-TINCR-CALML5-SFN network is thus essential for epidermal differentiation.

Single-stage interpolation flaps in facial reconstruction.

BACKGROUND: Relatively deep and complex surgical defects, particularly when adjacent to or involving free margins, present significant reconstructive challenges. When the use of local flaps is precluded by native anatomic restrictions, interpolation flaps may be modified to address these difficult wounds in a single operative session. OBJECTIVE: To provide a framework to approach difficult soft tissue defects arising near or involving free margins and to demonstrate appropriate design and execution of single-stage interpolation flaps for reconstruction of these wounds. METHODS: Examination of our utilization of these flaps based on an anatomic region and surgical approach. RESULTS: A region-based demonstration of flap conceptualization, design, and execution is provided. CONCLUSION: Tunneled, transposed, and deepithelialized variations of single-stage interpolation flaps provide versatile options for reconstruction of a variety of defects encroaching on or involving free margins. The inherently robust vascularity of these flaps supports importation of necessary tissue bulk while allowing aggressive contouring to restore an intricate native topography. Critical flap design allows access to distant tissue reservoirs and placement of favorable incision lines while preserving the inherent advantages of a single operative procedure.