Establishing Consensus for Mohs Micrographic Surgical Techniques in the Treatment of Melanoma in Situ for Future Clinical Trials: A Modified Delphi Study.

BACKGROUND: Mohs micrographic surgery (MMS) is a promising treatment modality for melanoma in situ (MIS). However, variations in surgical technique limit the generalizability of existing data and may impede future study of MMS in clinical trials. METHODS: A modified Delphi method was selected to establish consensus on optimal MMS techniques for treating MIS in future clinical trials. The Delphi method was selected due to the limited current data, the wide range of techniques used in the field, and the intention to establish a standardized technique for future clinical trials. A literature review and interviews with experienced MMS surgeons were performed to identify dimensions of the MMS technique for MIS that (1) likely impacted costs or outcomes of the procedure, and (2) showed significant variability between surgeons. A total of 8 dimensions of technical variation were selected. The Delphi process consisted of 2 rounds of voting and commentary, during which 44 expert Mohs surgeons across the United States rated their agreement with specific recommendations using a Likert scale. RESULTS: Five of eight recommendations achieved consensus in Round 1. All 3 of the remaining recommendations achieved consensus in Round 2. Techniques achieving consensus in Round 1 included the use of a starting peripheral margin of ≤5 mm, application of immunohistochemistry, frozen tissue processing, and resecting to the depth of subcutaneous fat. Consensus on the use of Wood's lamp, dermatoscope, and negative tissue controls was established in Round 2. CONCLUSIONS: This study generated 8 consensus recommendations intended to offer guidance for Mohs surgeons treating MIS. The adoption of these recommendations will promote standardization to facilitate comparisons of aggregate data in multicenter clinical trials.

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.

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.

Periorbital reconstructive techniques following Mohs micrographic surgery or excisions: a systematic review.

There are many articles in the literature on periorbital reconstruction after Mohs micrographic surgery (MMS) or surgical excision, however, the literature lacks a comprehensive systematic review of these reports. We performed a systematic review of published data on periorbital defect reconstruction to identify trends in the literature. A comprehensive search of eight databases was performed. To be included in the study, articles had to be published in English between 2005 and 2020 and contain repair data for MMS or excision defects in the periorbital region. Studies with less than four patients, literature or systematic reviews, and abstract-only publications were excluded. Data extracted from eligible articles included the authors' medical specialties, study design, subject number and demographics, defect characteristics, procedure type, reconstructive methods, complications, outcome measures, and method of outcome assessment. 53 studies met the inclusion criteria. The first and last authors' specialties were ophthalmology (47%), plastic and reconstructive surgery (23%), dermatology (13%), otolaryngology (4%), or were multi-specialty collaborations (13%). Only 5 of the studies were prospective. Defects were located on the lower eyelid (55%), medial canthus (31%), upper eyelid (8%), lateral canthus (4%), or a combination of these sites (2%). Reconstructive methods were reported for 3678 cases and included linear repair (18%), advancement flap (8%), rotation flap (5%), transposition flap (3%), island pedicle flap (1%), unspecified local skin flap (21%), skin graft (23%), secondary intention (4%), tarsoconjunctival flap (3%), and combined reconstruction techniques (13%). Thirty-three of 53 articles specified the periorbital subunit for each reconstructive technique that was employed. Among these 33 articles which allowed for correlation between defect location and reconstructive technique, the most utilized repair method for lower eyelid defects was local skin flap. Defects on the upper eyelid or medial canthus were most frequently repaired with a skin graft. Forty articles commented on cosmetic outcomes, however, only 3 of these articles utilized a defined grading system, objective measurements, or independent reviewers to assess the cosmetic outcomes. The methods of reconstruction in this review were diverse, however, local skin flaps and grafts were the most utilized techniques. In future reports, increased reporting of reconstructive technique by defect location as well as increased use of standardized assessments of aesthetic outcomes can help strengthen this body of literature.

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.

Repair of auricular defects following Mohs micrographic surgery or excision: a systematic review of the literature.

Repair of auricular defects following tumor removal can be challenging. Many techniques have been described, but the literature lacks a comprehensive review of these methods. To perform a systematic review to compile and describe methods of reconstruction for post-surgical defects on the ears, eight databases were searched using terms related to ear anatomy, Mohs and excisions, and repair methods. Articles were eligible for inclusion if they contained repair data for ear defects following Mohs or excision for at least 4 subjects and were published in English between 2004 and 2019. Two reviewers screened all abstracts, and then evaluated the remaining full text articles to determine eligibility. The authors' specialties, study design, subject information, tumor and defect characteristics, procedure, repair methods, outcomes, and complications were then extracted. Most articles were written by dermatologic surgeons (66.7%). Repair methods included wedge excisions (19 cases), second intention healing (376), linear closures (294), purse strings (4), locoregional flaps (221), and grafts (2003). Most studies were small observational case series or cohort studies that lacked clear outcome measures. The available evidence on this topic is low quality. Further research utilizing improved study designs and standardized outcome measures is needed.

One-sized bilobed flap does not fit all standing cones: a mathematical analysis of the standing cone in bilobed flap dynamics.

The bilobed flap (BLF) is a workhorse for nasal repair. Alterations to the length and orientation of the BLF's standing cutaneous deformity (SCD) have been suggested as a means of preventing Z-plasty-induced flap lengthening and consequent ipsilateral alar depression. To investigate the effect of design variations of the SCD on bilobed flap mechanics. Geometric analysis of the BLF was performed using commercially available graphing software. BLFs were designed with a SCD equal to one radius (rBLF) and one diameter (dBLF) of the primary defect as well as with a more superiorly-oriented one diameter SCD (soBLF). Lengths from the pivot point to the distal edges of the primary defect and primary lobe were measured and compared. Elongation or a more superior orientation of the SCD without changes to the rest of the flap design forms a primary lobe along a shorter arc resulting in insufficient flap length to resurface the primary defect. The insufficient length requires secondary motion to complete the repair and possible unintended alar displacement. Modification of the size and orientation of the SCD alters the location of the pivot point, which is a key determinant of BLF mechanics. Therefore, changes to the SCD require alterations to the remainder of the flap design to ensure aesthetic and functional success.

Nasal reconstructive techniques following Mohs surgery or excisions: a systematic review.

Numerous reconstructive techniques for nasal defects following skin cancer removal have been described; however, the literature lacks a comprehensive systematic review. Our objective was to systematically review nasal reconstruction methods after tumor removal, correlate the use of specific techniques to the nasal subunits involved, assess the quality of the available evidence, and set the stage for future research on this topic. Eight databases were searched for studies published in English from January 2004 to December 2018 containing repair data for nasal defects following Mohs or excision for four or more subjects. Recorded data included author specialties, study design, subject number, demographics, defect characteristics, procedure type, reconstructive methods, outcome measures, and complications. One-hundred and eleven studies were included. Study types included case series (73%), observational cohort studies (25%), and clinical trials (2%). Most authors were dermatologic surgeons (61%). Resection was most commonly performed via Mohs (82%). Flaps (42%), linear closures (28%) and grafts (25%) were most utilized for reconstruction. In Zones I and II, transposition flaps were the most common followed by advancement flaps. In Zone III, full thickness skin grafts were the most common repair. Most studies were case series or small cohort studies, representing low level evidence. Flaps are the most common method described in the literature for nasal reconstruction. The overall quality of the evidence available on this topic is low.

Cheek Donor Site for Full-Thickness Skin Graft Repair of the Nasal Ala: Outcomes of a Retrospective Cohort Study.

BACKGROUND: Full-thickness skin grafts (FTSGs) are useful repairs for reconstructing nasal alar defects. Traditional donor sites include the preauricular, postauricular, and supraclavicular skin. OBJECTIVE: To evaluate esthetic outcomes and complications of nasal alar defects repaired with FTSGs from the medial cheek. MATERIALS AND METHODS: A retrospective chart review of Mohs surgery patients who had FTSG repair of the nasal ala between January 2015 and August 2020 was performed. Demographic, surgery, and follow-up visit data were reviewed. Cosmesis was rated by a facial plastic surgeon, a Mohs surgeon, and a plastic surgeon using baseline, defect, and follow-up visit photographs. RESULTS: Sixty-nine patients with FTSG repairs of nasal alar defects were identified. 51 of 69 patients (73.9%) had the cheek donor site, and 18 of 69 patients (26.1%) had a noncheek donor site. The mean (SD) rater visual analog score for both cohorts was good with no significant difference (cheek: 65.9 [13.8]; noncheek: 66.1 [15.3]; p = .96). A notable difference in the complication rate by donor site was observed (cheek: 6.9%, noncheek: 16.7%; p = .13), although it did not reach significance. CONCLUSION: The cheek is a reliable FTSG donor site for nasal alar defects after Mohs micrographic surgery, with a trend toward fewer complications.

Nonmelanoma Skin Cancer in Patients Older Than Age 85 Years Presenting for Mohs Surgery: A Prospective, Multicenter Cohort Study.

Importance: It has been suggested that Mohs surgery for skin cancer among individuals with limited life expectancy may be associated with needless risk and discomfort, along with increased health care costs. Objective: To investigate patient- and tumor-specific indications considered by clinicians for treatment of nonmelanoma skin cancer in older individuals. Design, Setting, and Participants: This multicenter, prospective cohort study was conducted using data from US private practice and academic centers. Included patients were those older than age 85 years presenting for skin cancer surgery and referred for Mohs surgery, with reference groups of those younger than age 85 years receiving Mohs surgery and those older than age 85 years not receiving Mohs surgery. Data were analyzed from November 2018 through January 2019. Exposures: Mohs surgery for nonmelanoma skin cancer. Main Outcomes and Measures: Reason for treatment selection. Results: Among 1181 patients older than age 85 years referred for Mohs surgery (724 [61.9%] men among 1169 patients with sex data; 681 individuals aged >85 to 88 years [57.9%] among 1176 patients with age data) treated at 22 sites, 1078 patients (91.3%) were treated by Mohs surgery, and 103 patients (8.7%) received alternate treatment. Patients receiving Mohs surgery were more likely to have tumors on the face (738 patients [68.5%] vs 26 patients [25.2%]; P < .001) and nearly 4-fold more likely to have high functional status (614 patients [57.0%] vs 16 patients [15.5%]; P < .001). Of 15 distinct reasons provided by surgeons for opting to proceed with Mohs surgery, the most common were patient desire for treatment with a high cure rate (712 patients [66.0%]), good or excellent patient functional status for age (614 patients [57.0%]), and high risk associated with the tumor based on histology (433 patients [40.2%]). Conclusions and Relevance: This study found that older patients who received Mohs surgery often had high functional status, high-risk tumors, and tumors located on the face. These findings suggest that timely surgical treatment may be appropriate in older patients given that their tumors may be aggressive, painful, disfiguring, and anxiety provoking.

Gene expression profiling for metastatic risk in head and neck cutaneous squamous cell carcinoma.

OBJECTIVE: Over 50% of newly diagnosed cutaneous squamous cell carcinoma (cSCC) lesions occur in the head and neck (cSCC-HN), and metastasis to nodal basins in this region further complicates surgical and adjuvant treatment. The current study addressed whether the 40-gene expression profile (40-GEP) test can predict metastatic risk in cSCC-HN with improved accuracy and provide independent prognostic value to complement current risk assessment methods. STUDY DESIGN: Multicenter, retrospective cohort study. METHODS: Formalin-fixed paraffin-embedded primary tumor tissue and associated clinical data from patients with cSCC-HN (n = 278) were collected from 33 independent centers. Samples were analyzed via the 40-GEP test. Cases were staged per American Joint Committee on Cancer, Eighth Edition (AJCC8) and Brigham and Women's Hospital (BWH) criteria after comprehensive medical record and pathology report review. Metastasis-free survival (MFS) rates were determined, and risk factors were analyzed via Cox regression. RESULTS: The 40-GEP test classified the cohort into low (Class 1, n = 126; 45.3%), moderate (Class 2A, n = 134; 48.2%), and high (Class 2B, n = 18; 6.5%) metastatic risk at 3 years postdiagnosis. Regional/distant metastasis occurred in 54 patients (19.4%). MFS rates were 92.1% (Class 1), 76.1% (Class 2A), and 44.4% (Class 2B; p < .0001). Multivariate analysis of 40-GEP results with AJCC8 or BWH tumor stage, or clinicopathologic risk factors, demonstrated independent prognostic value of the 40-GEP test (p < .03). Accuracy of predicting metastatic risk was also improved using 40-GEP classification (p < .02). CONCLUSIONS: Improved metastatic risk stratification through the 40-GEP test could complement cSCC-HN risk assessment for better-informed decision-making for treatment and surveillance and ultimately improve patient outcomes. LEVEL OF EVIDENCE: 3.

Protocol for development of a core outcome set for clinical trials in melasma.

INTRODUCTION: Melasma is a pigmentation disorder of the skin. Characterised by brown to gray-brown patches on the face and neck, the condition predominantly affects women and has been associated with pregnancy, hormonal variation and sun exposure. Melasma can be disfiguring and anxiety-provoking, and quality of life is often adversely impacted. Management includes sun protection, laser and energy device therapy, topical and oral skin-bleaching agents and chemical peels. While clinical trials of melasma exist, there is a lack of consistency in reported outcomes, which has been a barrier to the aggregation of data in systematic reviews and meta-analyses. This protocol describes a planned process for development of a minimum set of outcomes (ie, 'core outcome set') that should be measured in all clinical trials of melasma. METHODS AND ANALYSIS: An exhaustive list of potential outcomes will be extracted from four sources: (1) systematic literature review of outcomes in clinical trials; (2) semistructured patient interviews; (3) brochures, pamphlets, clinical trial registries, and other published and unpublished sources and documentation; and (4) interviews with non-patient, non-physician stakeholders, including federal regulators, industry scientists and non-physician providers. An international two-round Delphi process will then be performed to identify the outcomes deemed most important to patients and physicians. Subsequently, a consensus meeting will be convened to review and process the results, and to vote on a final set of core outcomes. ETHICS AND DISSEMINATION: Ethics approval was provided by the Northwestern University Institutional Review Board (protocol ID: STU00201637). This study is registered with both the Core Outcome Measures in Effectiveness Trials and Cochrane Skin-Core Outcome Set Initiative initiatives, and this protocol is in accordance with the guidelines for protocol development of both groups. All findings from the study described in this protocol will be disseminated to all stakeholders involved in the development process and will be submitted for publication in peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42020214189.

Evidence-Based Clinical Practice Guidelines for Extramammary Paget Disease.

IMPORTANCE: Extramammary Paget disease (EMPD) is a frequently recurring malignant neoplasm with metastatic potential that presents in older adults on the genital, perianal, and axillary skin. Extramammary Paget disease can precede or occur along with internal malignant neoplasms. OBJECTIVE: To develop recommendations for the care of adults with EMPD. EVIDENCE REVIEW: A systematic review of the literature on EMPD from January 1990 to September 18, 2019, was conducted using MEDLINE, Embase, Web of Science Core Collection, and Cochrane Libraries. Analysis included 483 studies. A multidisciplinary expert panel evaluation of the findings led to the development of clinical care recommendations for EMPD. FINDINGS: The key findings were as follows: (1) Multiple skin biopsies, including those of any nodular areas, are critical for diagnosis. (2) Malignant neoplasm screening appropriate for age and anatomical site should be performed at baseline to distinguish between primary and secondary EMPD. (3) Routine use of sentinel lymph node biopsy or lymph node dissection is not recommended. (4) For intraepidermal EMPD, surgical and nonsurgical treatments may be used depending on patient and tumor characteristics, although cure rates may be superior with surgical approaches. For invasive EMPD, surgical resection with curative intent is preferred. (5) Patients with unresectable intraepidermal EMPD or patients who are medically unable to undergo surgery may receive nonsurgical treatments, including radiotherapy, imiquimod, photodynamic therapy, carbon dioxide laser therapy, or other modalities. (6) Distant metastatic disease may be treated with chemotherapy or individualized targeted approaches. (7) Close follow-up to monitor for recurrence is recommended for at least the first 5 years. CONCLUSIONS AND RELEVANCE: Clinical practice guidelines for EMPD provide guidance regarding recommended diagnostic approaches, differentiation between invasive and noninvasive disease, and use of surgical vs nonsurgical treatments. Prospective registries may further improve our understanding of the natural history of the disease in primary vs secondary EMPD, clarify features of high-risk tumors, and identify superior management approaches.