Rosacea Core Domain Set for Clinical Trials and Practice: A Consensus Statement.

Importance: Inconsistent reporting of outcomes in clinical trials of rosacea is impeding and likely preventing accurate data pooling and meta-analyses. There is a need for standardization of outcomes assessed during intervention trials of rosacea. Objective: To develop a rosacea core outcome set (COS) based on key domains that are globally relevant and applicable to all demographic groups to be used as a minimum list of outcomes for reporting by rosacea clinical trials, and when appropriate, in clinical practice. Evidence Review: A systematic literature review of rosacea clinical trials was conducted. Discrete outcomes were extracted and augmented through discussions and focus groups with key stakeholders. The initial list of 192 outcomes was refined to identify 50 unique outcomes that were rated through the Delphi process Round 1 by 88 panelists (63 physicians from 17 countries and 25 patients with rosacea in the US) on 9-point Likert scale. Based on feedback, an additional 11 outcomes were added in Round 2. Outcomes deemed to be critical for inclusion (rated 7-9 by ≥70% of both groups) were discussed in consensus meetings. The outcomes deemed to be most important for inclusion by at least 85% of the participants were incorporated into the final core domain set. Findings: The Delphi process and consensus-building meetings identified a final core set of 8 domains for rosacea clinical trials: ocular signs and symptoms; skin signs of disease; skin symptoms; overall severity; patient satisfaction; quality of life; degree of improvement; and presence and severity of treatment-related adverse events. Recommendations were also made for application in the clinical setting. Conclusions and Relevance: This core domain set for rosacea research is now available; its adoption by researchers may improve the usefulness of future trials of rosacea therapies by enabling meta-analyses and other comparisons across studies. This core domain set may also be useful in clinical practice.

Frozen Section Histoanatomy of the Peritarsal Eyelid.

BACKGROUND: Mohs surgery of eyelid skin cancers requires detailed knowledge of anatomy for precise surgery and accurate evaluation of histology. OBJECTIVE: To review the histology of the peritarsal eyelid using frozen sections as encountered intraoperatively by Mohs surgeons. METHODS: The authors review the literature describing the anatomy and histology of the peritarsal eyelid from the lens of a Mohs surgeon. Histology from select Mohs cases is used to frame the discussion of the microanatomy of this region. RESULTS: The peritarsal eyelids contain a unique mixture of skin, muscle, tarsus, glandular tissue, and conjunctiva. The histologic appearance of many of these structures differs from skin found outside of this anatomic region. Tumors of the eyelid and periocular region may mimic normal histologic structures found within the peritarsal eyelid. CONCLUSION: The peritarsal eyelids have unique anatomy and associated histologic structures. Knowledge of the detailed histoanatomy is required for confident execution of Mohs surgery in this anatomic region.

Anticipated Versus Unanticipated Incomplete Mohs Micrographic Surgery for Keratinocyte Carcinomas: Impact on Treatment Delays and Final Margin Status.

BACKGROUND: Mohs micrographic surgery may be discontinued with positive margins as an anticipated strategy for multidisciplinary care or as an unanticipated occurrence. Management of primary tumors has not been compared after anticipated versus unanticipated incomplete Mohs micrographic surgery (iMMS). OBJECTIVE: To compare rates and timing of adjuvant surgery after iMMS and final margin status when iMMS is anticipated versus unanticipated. Secondary outcomes were preoperative and intraoperative clinicopathologic factors associated with iMMS. METHODS: Cases of iMMS of keratinocyte carcinomas at a tertiary academic center between 2005 and 2022 were classified as anticipated (preoperative assembly of multidisciplinary teams) or unanticipated (ad hoc management of positive margins). Rate, timing, and final margin status of adjuvant surgery was compared between anticipated and unanticipated iMMS cohorts using χ2/Fisher exact test for categorical variables and t-test for continuous variables. RESULTS: Of 127 iMMS cases, 51.2% (65/127) were anticipated. Anticipated iMMS cases were more likely to undergo additional resection (98.5% vs 72.6%, p < .001), with fewer delays (3.9 vs 13.2 days, p < .001) and higher rates of final margin clearance (84.6% vs 59.7%, p < .001). CONCLUSION: When iMMS is anticipated as part of multidisciplinary care, patients are more likely to undergo additional resection, with fewer delays to next surgery and higher final margin clearance rates.

Patient Preferences for Pain Control After Mohs Micrographic Surgery: A Single-Center Discrete Choice Experiment.

Importance: Patient preferences for pain medications after Mohs micrographic surgery are important to understand and have not been fully studied. Objective: To evaluate patient preferences for pain management with only over-the-counter medications (OTCs) or OTCs plus opioids after Mohs micrographic surgery given varying levels of theoretical pain and opioid addiction risk. Design, Setting, and Participants: This prospective discrete choice experiment was conducted in a single academic medical center from August 2021 to April 2022 among patients undergoing Mohs surgery and their accompanying support persons (≥18 years). A prospective survey was administered to all participants using the Conjointly platform. Data were analyzed from May 2022 to February 2023. Main outcome and measure: The primary outcome was the pain level at which half of the respondents chose OTCs plus opioids equally to only OTCs for pain management. This pain threshold was determined for varying opioid addiction risk profiles (low, 0%; low-moderate, 2%; moderate-high, 6%; high, 12%) and measured via a discrete choice experiment and linear interpolation of associated parameters (pain levels and risk of addiction). Results: Of the 295 respondents (mean [SD] age, 64.6 [13.1] years; 174 [59%] were female; race and ethnicity were not considered) who completed the discrete choice experiment, 101 (34%) stated that they would never consider opioids for pain management regardless of the pain level experienced, and 147 (50%) expressed concern regarding possible opioid addiction. Across all scenarios, 224 respondents (76%) preferred only OTCs vs OTCs plus opioids after Mohs surgery for pain control. When the theoretical risk of addiction was low (0%), half of the respondents expressed a preference for OTCs plus opioids given pain levels of 6.5 on a 10-point scale (90% CI, 5.7-7.5). At higher opioid addiction risk profiles (2%, 6%, 12%), an equal preference for OTCs plus opioids and only OTCs was not achieved. In these scenarios, patients favored only OTCs despite experiencing high levels of pain. Conclusion and relevance: The findings of this prospective discrete choice experiment indicate that the perceived risk of opioid addiction affects the patient's choice of pain medications after Mohs surgery. It is important to engage patients undergoing Mohs surgery in shared decision-making discussions to determine the optimal pain control plan for each individual. These findings may encourage future research on the risks associated with long-term opioid use after Mohs surgery.

A Cost Comparison Between Mohs Micrographic Surgery and Conventional Excision for the Treatment of Head and Neck Melanomas In Situ and Thin Melanomas.

BACKGROUND: Variation in operative setting and surgical technique exists when treating specialty site melanomas. There are limited data comparing costs among surgical modalities. OBJECTIVE: To evaluate the costs of head and neck melanoma surgery performed with Mohs micrographic surgery or conventional excision in the operating room or office-based settings. METHODS: A retrospective cohort study was performed on patients aged 18 years and older with surgically treated head and neck melanoma in 2 cohorts, an institutional cohort and an insurance claims cohort, for the years 2008-2019. The primary outcome was total cost of care for a surgical encounter, provided in the form of insurance reimbursement data. A generalized linear model was used to adjust for covariates affecting differences between treatment groups. RESULTS: In the institutional and insurance claims cohorts, average adjusted treatment cost was highest in the conventional excision-operating room treatment group, followed by the Mohs surgery and conventional excision-office setting ( p < .001). CONCLUSION: These data demonstrate the important economic role the office-based setting has for head and neck melanoma surgery. This study allows cutaneous oncologic surgeons to better understand the costs of care involved in head and neck melanoma treatment. Cost awareness is important for shared decision-making discussions with patients.

Postoperative Complications After Interpolated Flap Repair for Mohs Defects of the Nose: A Multicenter Prospective Cohort Study.

BACKGROUND: Dermatologists perform most interpolated flaps after skin cancer resection. Prospective, multicenter data on complications after interpolated flap repair in this setting are limited. OBJECTIVE: To determine the rate of physician-reported complications after interpolated flap repair of the nose. METHODS: Multicenter, prospective cohort study of 169 patients undergoing 2-stage interpolated flap repair of post-Mohs nasal defects. Frequency of bleeding, infection, dehiscence, necrosis, hospitalization, and death in the 30 days after flap placement and flap takedown are reported. RESULTS: Patients experienced 23 complications after flap placement (13.61%) and 6 complications after flap takedown (3.55%) that were related to the surgical procedure. The most frequent complication after flap placement was bleeding (9, 5.33%, 95% confidence interval [CI]: 2.83%-9.82%). The most frequent complication after flap takedown was infection (5, 2.96%, 95% CI: 1.27%-6.74%). There was one hospitalization related to an adverse reaction to antibiotics. There were no deaths. CONCLUSION: Most complications after interpolated flap repair for post-Mohs defects of the nose are minor and are associated with flap placement. Interpolated flap repair for post-Mohs defects can be performed safely in the outpatient setting under local anesthesia.

Outcomes of invasive melanoma of the head and neck treated with Mohs micrographic surgery - A multicenter study.

BACKGROUND: There are no randomized controlled trials to guide surgical margins for invasive head and neck (H&N) melanoma using conventional excision. Mohs micrographic surgery (MMS) has shown improved local recurrence rates and survival for invasive H&N melanomas. OBJECTIVE: Determine local recurrence (LR), nodal recurrence, and distant recurrence rates, and disease specific survival for invasive melanoma of the H&N treated with MMS. METHODS: A retrospective multicenter study of 785 cases of invasive H&N melanoma treated with MMS using frozen sections with melanoma antigen recognized by T-cells 1 immunohistochemical staining was performed to evaluate long-term outcomes over 12-years. RESULTS: 785 melanomas (thickness: 0.3 mm-8.5 mm) were treated with MMS. LR, nodal recurrence, and distant recurrence rates were 0.51% (4/785), 1.0% (8/785), and 1.1% (9/785) respectively. For T1, T2, T3, and T4 tumors LR was 0.16% (1/636), 1.18% (1/85), 2.22% (1/45), and 5.26% (1/19), respectively. Five and 10-year disease specific survival were 96.8% (95% CI 95.0% to 98.5%) and 93.4% (95% CI 88.5% to 98.3%). LIMITATIONS: A nonrandomized retrospective study. CONCLUSION: MMS achieves significant improvements in LR compared to a meta-analysis of historical cohorts of patients treated with conventional excision. MMS should be considered an important surgical option for invasive H&N melanoma.

Merkel Cell Carcinoma.

Merkel cell carcinoma (MCC) is a neuroendocrine carcinoma that typically presents as a rapidly enlarging violaceous papulonodule on sun-damaged skin in elderly patients. MCC has high rates of local recurrence, metastasis, and poor survival. Treatment of the primary tumor involves surgical excision with possible adjuvant radiation therapy, whereas regional nodal disease is treated with some combination of lymph node dissection and radiation therapy. Immune checkpoint inhibitors, such as avelumab and pembrolizumab, are first-line agents for metastatic MCC. Monitoring for recurrence can be aided by Merkel cell polyomavirus oncoprotein antibody titers.

Performing research and publishing in the peer-reviewed medical literature should be a requirement for completion of post-graduate residency and fellowship training.

Graduate medical education (GME) in the USA is an increasingly organized and formalized process overseen by regulatory bodies, notably the American Council of Graduate Medical Education (ACGME), and associated specialty-specific Residency Review Committees (RRCs) to ensure that trainees, including residents and fellows, receive comprehensive, high-quality didactic education, clinical training, and research experience. Among the required elements of GME, performance of independent research is emphasized less than clinical and didactic education. In general, there are no ACGME requirements that trainees successfully publish papers in the peer reviewed. Indeed, unlike as is the case with procedure case logs, there are no minimum thresholds for specific numbers of abstracts presented, posters accepted, or manuscripts published. As such, while residencies and fellowships in certain disciplines or institutions may require considerable, documented research activity, others may not. Since future attending physicians are expected to be experts in their fields, able to digest relevant medical knowledge, critically evaluate emerging findings in the literature, and lead multi-professional healthcare teams, they must have a level of facility with the medical literature than can only be acquired by having performed research and having published papers themselves. Publishing one paper during training is easily attainable for all trainees. Having this be an ACGME requirement will necessitate protected time, research methods education, and mentorship for trainees. This can be accomplished without disrupting the other elements of resident and fellow training. From an ACGME perspective, required scholarly activity will support the competencies of practice-based learning and improvement as well as professionalism. In lay terms, benefits will be a higher level of education and attainment for trainees, and a potentially higher standard of health care for our patients.

Patient-Reported Nasal Function and Appearance After Interpolation Flap Repair Following Skin Cancer Resection: A Multicenter Prospective Cohort Study.

Objective: Among patients undergoing two-stage interpolated flap repair of nasal defects, nasal function, and appearance before surgery and at 16 weeks after flap takedown were compared using the Nasal Appearance and Function Evaluation Questionnaire (NAFEQ). Design: Multicenter prospective cohort study. Methods: Adult patients with a nasal skin cancer anticipated to require two-stage interpolation flap repair completed the NAFEQ before surgery, at 1 week after flap placement, 4 weeks after flap takedown, and 16 weeks after flap takedown. Results: One hundred sixty-nine patients were enrolled, with 138 patients completing both presurgical and 16-week post-takedown NAFEQs. Overall NAFEQ score increased by 1.09 points (1.91% improvement, confidence interval [95% CI -0.34 to 2.53]). NAFEQ functional subscale increased by 0.72 points (2.58% increase; 95% CI [0.10-1.35]) and appearance subscale increased by 0.37 points (1.28% improvement, 95% CI [-0.65 to 1.39]). Conclusion: At 16 weeks after flap takedown, patients' perceptions of their nasal function and appearance are similar to or slightly improved when compared with their presurgical assessments.

Evidence-Based Clinical Practice Guidelines for Laser-Assisted Drug Delivery.

Importance: Laser-assisted drug delivery (LADD) is used for various medical and cosmetic applications. However, there is insufficient evidence-based guidance to assist clinicians performing LADD. Objective: To develop recommendations for the safe and effective use of LADD. Evidence Review: A systematic literature review of Cochrane Central Register of Controlled Trials, Embase, and MEDLINE was conducted in December 2019 to identify publications reporting research on LADD. A multidisciplinary panel was convened to draft recommendations informed by the systematic review; they were refined through 2 rounds of Delphi survey, 2 consensus meetings, and iterative review by all panelists until unanimous consensus was achieved. Findings: Of the 48 published studies of ablative fractional LADD that met inclusion criteria, 4 were cosmetic studies; 21, oncologic; and 23, medical (not cosmetic/oncologic), and 6 publications of nonablative fractional LADD were included at the request of the expert panel, producing a total of 54 studies. Thirty-four studies (63.0%) were deemed to have low risk of bias, 17 studies (31.5%) had moderate risk, and 3 (5.5%) had serious risk. The key findings that informed the guidelines developed by the expert panel were as follows: LADD is safe in adults and adolescents (≥12 years) with all Fitzpatrick skin types and in patients with immunosuppression; it is an effective treatment for actinic keratosis, cutaneous squamous cell carcinoma in situ, actinic cheilitis, hypertrophic scars, and keloids; it is useful for epidermal and dermal analgesia; drug delivery may be increased through the application of heat, pressure, or occlusion, or by using an aqueous drug solution; laser settings should be selected to ensure that channel diameter is greater than the delivered molecule; antibiotic prophylaxis is not recommended, except with impaired wound healing; antiviral prophylaxis is recommended when treating the face and genitalia; and antifungal prophylaxis is not recommended. The guideline's 15 recommendations address 5 areas of LADD use: (I) indications and contraindications; (II) parameters to report; (III) optimization of drug delivery; (IV) safety considerations; and (V) prophylaxis for bacterial, viral, and fungal infections. Conclusions and Relevance: This systematic review and Delphi consensus approach culminated in an evidence-based clinical practice guideline for safe and effective use of LADD in a variety of applications. Future research will further improve our understanding of this novel treatment technique.

One- and two-staged Pacman V-Y advancement flaps for defects of the head and neck: A review of 29 cases.

BACKGROUND: When traditional V-Y advancement flaps cannot span cutaneous defects, the modified Pacman™ V-Y advancement flap (Pacman™ VYAF) design increases its utility for challenging facial defects. OBJECTIVE: To describe the usage and surgical outcomes of Mohs micrographic surgery (MMS) defects repaired with the Pacman™ VYAF. METHODS: A retrospective review was performed on MMS defects repaired with the Pacman™ VYAF in the division of dermatologic surgery at a large academic institution between January 01, 2013 and August 01, 2019. RESULTS: Twenty-nine instances of Pacman™ VYAF reconstructions were identified. Reconstruction of the cheek (22/29, 76%) was the most common, followed by the temple (4/29, 14%), and the post-auricular neck (3/29, 10%). Distal flap necrosis occurred more frequently in large Pacman™ VYAF repairs (6/29, 21% of cases), requiring surgical revision in 1 case. Surgical scars from the Pacman™ VYAF are rated favorably by dermatologic surgeons. CONCLUSION: The Pacman™ VYAF is a useful reconstruction option for surgical defects of the head and neck, and it is advantageous compared to traditional V-Y advancement flaps for defects with length greater than width.