TLR3 activation mediates partial epithelial-to-mesenchymal transition in human keratinocytes.

TLR3 is expressed in human skin and keratinocytes, and given its varied role in skin inflammation, development, and regeneration, we sought to determine the cellular response in normal human keratinocytes to TLR3 activation. We investigated this mechanism by treating primary human keratinocytes with both UVB, an endogenous and physiologic TLR3 activator, and poly(I:C), a synthetic and selective TLR3 ligand. TLR3 activation with either UVB or poly(I:C) altered keratinocyte morphology, coinciding with the key features of epithelial-to-mesenchymal transition: increased epithelial-to-mesenchymal transition gene expression, enhanced migration, and increased invasion properties. These results confirm and extend previous studies demonstrating that in addition to its classical role in the innate immune response, TLR3 signaling also regulates stem cell-like properties and developmental programs.

Surgical Debulking Modifies Notch Signaling and May Improve Vismodegib Effectiveness for Locally Advanced Basal Cell Carcinoma.

Smoothened inhibitors, such as vismodegib, exhibit remarkable success in treating patients with locally advanced basal cell carcinoma (LaBCC). Yet, vismodegib efficacy is hindered by notable side effects, which often lead to treatment discontinuation and subsequent relapse in patients with LaBCC. Prolonged remission was previously reported in patients with LaBCCs who underwent surgical debulking before starting vismodegib. In this study, we enrolled 4 patients with LaBCC who underwent debulking followed by vismodegib therapy to assess their clinical outcomes and analyze the cutaneous molecular changes occurring as a result of surgical intervention. After LaBCC debulking, patients underwent a punch biopsy of residual basal cell carcinoma tissue 1 week later. RT-qPCR analysis of 24 Notch and Wnt signaling-associated genes revealed elevated PTCH1, HEY2, LGR6, FZD2, LEF1, ALCAM, and RUNX1 expressions in follow-up biopsies compared with those in patient-matched debulked tissue. Immunoblot and immunostaining further confirmed elevated Notch signaling in follow-up biopsy tissue compared with that in patient-matched debulked tumor tissue. Patients 1, 3, and 4 displayed a clinical response to debulking followed by vismodegib, whereas patient 2 was lost to follow-up after debulking. These findings suggest that surgical manipulation of LaBCCs is correlated with molecular alterations in signaling pathways associated with cellular reprogramming.

5-Year Follow-Up of a Physician Performance Feedback Report Intervention to Reduce Overuse and Excess Cost: A National Cohort Study.

BACKGROUND: Mohs micrographic surgery efficiently treats skin cancer through staged resection, but surgeons' varying resection rates may lead to higher medical costs. OBJECTIVE: To evaluate the cost savings associated with a quality improvement. MATERIALS AND METHODS: The authors conducted a retrospective cohort study using 100% Medicare fee-for-service claims data to identify the change of mean stages per case for head/neck (HN) and trunk/extremity (TE) lesions before and after the quality improvement intervention from 2016 to 2021. They evaluated surgeon-level change in mean stages per case between the intervention and control groups, as well as the cost savings to Medicare over the same time period. RESULTS: A total of 2,014 surgeons performed Mohs procedures on HN lesions. Among outlier surgeons who were notified, 31 surgeons (94%) for HN and 24 surgeons (89%) for TE reduced their mean stages per case with a median reduction of 0.16 and 0.21 stages, respectively. Reductions were also observed among outlier surgeons who were not notified, reducing their mean stages per case by 0.1 and 0.15 stages, respectively. The associated total 5-year savings after the intervention was 92 million USD. CONCLUSION: The implementation of this physician-led benchmarking model was associated with broad reductions of physician utilization and significant cost savings.

Identifying critical quality metrics in Mohs Surgery: A national expert consensus process.

BACKGROUND: Amid a movement toward value-based healthcare, increasing emphasis has been placed on outcomes and cost of medical services. To define and demonstrate the quality of services provided by Mohs surgeons, it is important to identify and understand the key aspects of Mohs micrographic surgery (MMS) that contribute to excellence in patient care. OBJECTIVE: The purpose of this study is to develop and identify a comprehensive list of metrics in an initial effort to define excellence in MMS. METHODS: Mohs surgeons participated in a modified Delphi process to reach a consensus on a list of metrics. Patients were administered surveys to gather patient perspectives. RESULTS: Twenty-four of the original 66 metrics met final inclusion criteria. Broad support for the initiative was obtained through physician feedback. LIMITATIONS: Limitations of this study include attrition bias across survey rounds and participation at the consensus meeting. Furthermore, the list of metrics is based on expert consensus instead of quality evidence-based outcomes. CONCLUSION: With the goal of identifying metrics that demonstrate excellence in performance of MMS, this initial effort has shown that Mohs surgeons and patients have unique perspectives and can be engaged in a data-driven approach to help define excellence in the field of MMS.

Well-Being and Professional Fulfillment in Mohs Surgeons: An Explanatory Sequential Mixed-Method Design Study.

BACKGROUND: There are limited data evaluating specific themes of well-being and professional fulfillment in Mohs surgeons. OBJECTIVE: To identify factors that drive occupational distress and those that promote well-being and professional fulfillment among Mohs surgeons. METHODS: This is an explanatory sequential mixed-method study, using semistructured individual interviews. Common drivers of physician well-being and fulfillment were identified based on the independent assessment of the coding in the interview transcripts. RESULTS: This study reports the following qualitative themes: (1) gratitude for the chosen profession and relationships, (2) unrealistic standards of perfection that may have contributed to past career success but are unattainable and create emotional burden, and (3) ability to practice in a manner aligned with personal values promotes professional fulfillment. CONCLUSION: This study suggests that gratitude, self-compassion, and ability to practice in a manner aligned with personal values promote well-being and professional fulfillment in Mohs surgeons. Notably, we found that unrealistic standards of perfection and personal-organization practice incongruences contribute to burnout.

Development of a core outcome set for basal cell carcinoma.

BACKGROUND: There is variation in the outcomes reported in clinical studies of basal cell carcinoma. This can prevent effective meta-analyses from answering important clinical questions. OBJECTIVE: To identify a recommended minimum set of core outcomes for basal cell carcinoma clinical trials. METHODS: Patient and professional Delphi process to cull a long list, culminating in a consensus meeting. To be provisionally accepted, outcomes needed to be deemed important (score, 7-9, with 9 being the maximum) by 70% of each stakeholder group. RESULTS: Two hundred thirty-five candidate outcomes identified via a systematic literature review and survey of key stakeholders were reduced to 74 that were rated by 100 health care professionals and patients in 2 Delphi rounds. Twenty-seven outcomes were provisionally accepted. The final core set of 5 agreed-upon outcomes after the consensus meeting included complete response; persistent or serious adverse events; recurrence-free survival; quality of life; and patient satisfaction, including cosmetic outcome. LIMITATIONS: English-speaking patients and professionals rated outcomes extracted from English language studies. CONCLUSION: A core outcome set for basal cell carcinoma has been developed. The use of relevant measures may improve the utility of clinical research and the quality of therapeutic guidance available to clinicians.

Adjuvant radiotherapy may not significantly change outcomes in high-risk cutaneous squamous cell carcinomas with clear surgical margins: A systematic review and meta-analysis.

BACKGROUND: The role of adjuvant radiotherapy for high-risk cutaneous squamous cell carcinomas after surgery with negative margins is unclear. OBJECTIVE: To conduct a systematic review and meta-analysis examining the risk of poor outcomes for patients treated with surgery alone versus surgery and adjuvant radiotherapy. METHODS: A comprehensive search of articles was executed in PubMed, Embase, and the Cochrane Database. Random-effected meta-analyses were conducted. RESULTS: Thirty-three studies comprising 3867 high-risk cutaneous squamous cell carcinomas were included. There were no statistically significant differences in poor outcomes between the surgery only group and surgery with adjuvant radiotherapy group. Estimates for local recurrence for the surgery alone group versus the surgery with adjuvant radiotherapy group were 15.2% (95% confidence interval [CI], 6.3%-27%) versus 8.8% (95% CI, 1.6%-20.9%); for regional metastases, 11.5% (95% CI, 7.2%-16.7%) versus 4.4% (95% CI, 0%-18%); for distant metastases, 2.6% (95% CI, 0.6%-6%) versus 1.7% (95% CI, 0.2%-4.5%); and for disease-specific deaths, 8.2% (95% CI, 1.2%-20.6%) versus 19.7% (95% CI, 3.8%-43.7%), respectively. LIMITATIONS: Retrospective nature of most studies with the lack of sufficient patient-specific data. CONCLUSIONS: For patients with high-risk cutaneous squamous cell carcinomas treated with margin-negative resection, there were no significant differences in poor outcomes between the surgery only group and the surgery with adjuvant radiotherapy group. Randomized controlled trials are necessary to define the benefit of adjuvant radiotherapy in this setting.

Burnout and resiliency in Mohs surgeons: A survey study.

BACKGROUND: Physician burnout is a response to chronic work stress characterized by emotional exhaustion, depersonalization, and reduced sense of personal accomplishment. Resiliency is the ability to respond to chronic stress in a healthy and adaptive manner. No prior studies have specifically examined the prevalence of burnout and resilience in Mohs surgeons. OBJECTIVE: This study aimed to assess the current well-being of Mohs surgeons and specific resilient behaviors that can protect against burnout. METHODS: A cross-sectional electronic survey was sent to members of the American College of Mohs Micrographic Surgery. The survey combined the validated Maslach Burnout Inventory and The Resilience Profile ©. RESULTS: Of the 1450 surgeons registered with the American College of Mohs Surgery listserv, 137 (9.4%) participated in the survey. Of those who participated, 46% of surgeons had at least 1 symptom of burnout based on a high emotional exhaustion and/or high depersonalization score. Female surgeons (56%) were found to have higher levels of burnout compared with male surgeons (40%). Individual resilient behaviors protective of burnout include the ability to pivot and exhibition of self-control. CONCLUSION: Compared with all physicians and general dermatologists, Mohs surgeons have a lower rate of burnout. Similar to other surgical specialties, women report higher rates of burnout. Individual resilience factors that may be protective of burnout include ability to pivot and self-control.

An expert panel consensus on opioid-prescribing guidelines for dermatologic procedures.

BACKGROUND: Opioid overprescribing is a major contributor to the opioid crisis. The lack of procedure-specific guidelines contributes to the vast differences in prescribing practices. OBJECTIVE: To create opioid-prescribing consensus guidelines for common dermatologic procedures. METHODS: We used a 4-step modified Delphi method to conduct a systematic discussion among a panel of dermatologists in the fields of general dermatology, dermatologic surgery, and cosmetics/phlebology to develop opioid prescribing guidelines for some of the most common dermatologic procedural scenarios. Guidelines were developed for opioid-naive patients undergoing routine procedures. Opioid tablets were defined as oxycodone 5-mg oral equivalents. RESULTS: Postoperative pain after most uncomplicated procedures (76%) can be adequately managed with acetaminophen and/or ibuprofen. Group consensus identified no specific dermatologic scenario that routinely requires more than 15 oxycodone 5-mg oral equivalents to manage postoperative pain. Group consensus found that 23% of the procedural scenarios routinely require 1 to 10 opioid tablets, and only 1 routinely requires 1 to 15 opioid tablets. LIMITATIONS: These recommendations are based on expert consensus in lieu of quality evidence-based outcomes research. These recommendations must be individualized to accommodate patients' comorbidities. CONCLUSIONS: Procedure-specific opioid prescribing guidelines may serve as a foundation to produce effective and responsible postoperative pain management strategies after dermatologic interventions.

Collision Tumor of Basal and Squamous Cell Carcinoma of the Palm.

Nonmelanoma skin cancers, typically induced by ultraviolet light, are rarely found on the palmar aspects of the hands. Here, we describe a case of a basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) collision tumor on the palm of a 71-year-old woman. A brief review of literature regarding basal cell carcinoma of the palm and hand are provided, including etiology, diagnosis, and treatment recommendations.

Evaluation of a Peer-to-Peer Data Transparency Intervention for Mohs Micrographic Surgery Overuse.

IMPORTANCE: Mohs micrographic surgery (MMS) is a skin cancer treatment that uses staged excisions based on margin status. Wide surgeon-level variation exists in the mean number of staged resections used to treat a tumor, resulting in a cost disparity and question of appropriateness. OBJECTIVE: To evaluate the effectiveness of a behavioral intervention aimed at reducing extreme overuse in MMS, as defined by the specialty society, by confidentially sharing stages-per-case performance data with individual surgeons benchmarked to their peers nationally. DESIGN, SETTING, AND PARTICIPANTS: This nonrandomized controlled intervention study included 2329 US surgeons who performed MMS procedures from January 1, 2016, to March 31, 2018. Physicians were identified using a 100% capture of Medicare Part B claims. The intervention group included physicians affiliated with the American College of Mohs Surgery, and the control group included physicians not affiliated with the American College of Mohs Surgery. INTERVENTIONS: Individualized performance reports were delivered to all outlier surgeons, defined by the specialty society as those with mean stages per case 2 SDs above the mean, and inlier surgeons in the intervention group. MAIN OUTCOMES AND MEASURES: The primary outcome was surgeon-level change in mean stages per case between the prenotification (January 2016 to January 2017) and postnotification (March 2017 to March 2018) periods. A multivariable linear regression model was used to evaluate the association of notification with this surgeon-level outcome. The surgeon-level metric of mean stages per case was not risk adjusted. The mean Medicare cost savings associated with changes in practice patterns were calculated. RESULTS: Of the 2329 included surgeons, 1643 (70.5%) were male and 2120 (91.0%) practiced in metropolitan areas. In the intervention group (n = 1045), 53 surgeons (5.1%) were outliers; in the control group (n = 1284), 87 surgeons (6.8%) were outliers. Among the outliers in the intervention group, 44 (83%) demonstrated a reduction in mean stages per case compared with 60 outliers in the control group (69%; difference, 14%; 95% CI of difference, -1 to 27; P = .07). There was a mean stages-per-case reduction of 12.6% among outliers in the intervention group compared with 9.0% among outliers in the control group, and outliers in the intervention group had an adjusted postintervention differential decrease of 0.14 stages per case (95% CI, -0.19 to -0.09; P = .002). The total administrative cost of the intervention program was $150 000, and the estimated reduction in Medicare spending was $11.1 million. CONCLUSIONS AND RELEVANCE: Sharing personalized practice pattern data with physicians benchmarked to their peers can reduce overuse of MMS among outlier physicians.