Updates in Skin Cancer in Transplant Recipients and Immunosuppressed Patients: Review of the 2022-2023 Scientific Symposium of the International Immunosuppression and Transplant Skin Cancer Collaborative.

The International Immunosuppression and Transplant Skin Cancer Collaborative (ITSCC) and its European counterpart, Skin Care in Organ Transplant Patients-Europe (SCOPE) are comprised of physicians, surgeons, and scientist who perform integrative collaborative research focused on cutaneous malignancies that arise in solid organ transplant recipients (SOTR) and patients with other forms of long-term immunosuppression. In October 2022, ITSCC held its biennial 4-day scientific symposium in Essex, Massachusetts. This meeting was attended by members of both ITSCC and SCOPE and consisted of specialists including Mohs micrographic and dermatologic oncology surgeons, medical dermatologists, transplant dermatologists, transplant surgeons, and transplant physicians. During this symposium scientific workshop groups focusing on consensus standards for case reporting of retrospective series for invasive squamous cell carcinoma (SCC), defining immunosuppressed patient status for cohort reporting, development of multi-institutional registry for reporting rare tumors, and development of a KERACON clinical trial of interventions after a SOTRs' first cutaneous SCC were developed. The majority of the symposium focused on presentation of the most up to date research in cutaneous malignancy in SOTR and immunosuppressed patients with specific focus on chemoprevention, immunosuppression regimens, immunotherapy in SOTRs, spatial transcriptomics, and the development of cutaneous tumor registries. Here, we present a summary of the most impactful scientific updates presented at the 2022 ITSCC symposium.

Optimization of Tissue Digestion Methods for Characterization of Photoaged Skin by Single Cell RNA Sequencing Reveals Preferential Enrichment of T Cell Subsets.

Healthy human skin tissue is often used as a control for comparison to diseased skin in patients with skin pathologies, including skin cancers or other inflammatory conditions such as atopic dermatitis or psoriasis. Although non-affected skin from these patients is a more appropriate choice for comparison, there is a paucity of studies examining such tissue. This lack is exacerbated by the difficulty of processing skin tissue for experimental analysis. In addition, choosing a processing protocol for skin tissue which preserves cell viability and identity while sufficiently dissociating cells for single-cell analysis is not a trivial task. Here, we compare three digestion methods for human skin tissue, evaluating the cell yield and viability for each protocol. We find that the use of a sequential dissociation method with multiple enzymatic digestion steps produces the highest cell viability. Using single-cell sequencing, we show this method results in a relative increase in the proportion of non-antigen-presenting mast cells and CD8 T cells as well as a relative decrease in the proportion of antigen-presenting mast cells and KYNU+ CD4 T cells. Overall, our findings support the use of this sequential digestion method on freshly processed human skin samples for optimal cell yield and viability.

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.

Double V-Y Island Pedicle Flap for Dorsal Hand Reconstruction Following Mohs Micrographic Surgery.

Medium to large defects on the dorsal hand pose a reconstructive challenge following dermatologic surgery. Repairs in this location can be complicated by a paucity of adjacent tissue reservoirs, competing tension vectors, thin cutaneous tissue, and superficial tendons and vasculature. In such cases, a double V-Y island pedicle flap is an effective reconstructive solution. It preserves hand function, harnesses local tissue with a robust blood supply, facilitates complete closure, and provides skin that closely matches the original's color and texture. Here, we present the repair of a medium to large dorsal hand defect after Mohs micrographic surgery for melanoma in situ, using a double V-Y island pedicle flap.

Tranexamic Acid Prevention of Hemorrhagic Complications Following Interpolated Flap Repair: A Single-Center, Retrospective, Cohort Study.

BACKGROUND: Tranexamic acid (TXA) is increasingly being used to prevent hemorrhagic complications after dermatologic surgery. Interpolated flap repairs following Mohs micrographic surgery are at risk for increased bleeding events and unplanned health care utilization, particularly among patients on antithrombotic medication. OBJECTIVE: To assess bleeding events after interpolated flap repair in patients receiving TXA compared with those who did not. MATERIALS AND METHODS: A retrospective review identified interpolated flap repairs in a 5-year period. Hemorrhagic complications were analyzed, defined as major bleeding events, which included all unplanned medical visits, and minor bleeding events, which included any unplanned patient phone calls or messages through electronic medical record. RESULTS: One hundred fifteen patients had interpolated flap repair during the 5-year period, of which 21 (18.3%) received TXA postprocedure. Twenty-seven bleeding events were identified in the non-TXA group compared with 1 event in the TXA-treated group. Patients who received TXA were less likely to have had a bleeding event (28.7% vs 4.8%, p < .01). CONCLUSION: Patients undergoing interpolation flap repair were less likely to experience a bleeding event after subcutaneous injection of TXA.

Bilateral Transposition Flaps With Split-Thickness Skin Grafting of Secondary Defects After a Large Mohs Micrographic Surgery Defect With Exposed Calvarium.

Large, full-thickness defects of the scalp create a common reconstructive dilemma following Mohs micrographic surgery. In cases with exposed calvarium, transposition flap(s) followed by split-thickness skin graft(s) to the secondary defect is an effective method of reconstruction that allows for same-day repair, full defect coverage, and good functional outcomes. Herein, we present the reconstruction of a large scalp defect utilizing bilateral transposition flaps followed by split-thickness skin grafts of the secondary defects.

Efficacy of Abemaciclib in the Management of Refractory Metastatic Extramammary Paget's Disease.

Published systemic therapy options for metastatic extramammary Paget's disease have largely been anecdotal due to the rarity of this disease, which has precluded the ability to conduct clinical trials. We describe the favorable response of a 72-year-old man with extramammary Paget's disease, whose disease has been controlled with the CDK4/6 inhibitor, abemaciclib. The rationale behind the selection of this therapy is discussed.

Systematic Review of Technical Variations for Mohs Micrographic Surgery for Melanoma.

BACKGROUND: Mohs micrographic surgery (MMS) for cutaneous melanoma is becoming more prevalent, but surgical technique varies. OBJECTIVE: To define variations in published techniques for MMS for melanoma. METHODS AND MATERIALS: A systematic review was performed of PubMed, EMBASE, and Scopus databases to identify all articles describing surgical techniques for MMS for melanoma. Technical details were recorded for the preoperative, intraoperative, and postoperative phases of MMS. RESULTS: Twenty-four articles were included. Mohs surgeons vary in how they assess clinical margins, how wide a margin they excise on the first MMS layer, and how they process tissue to determine tumor stage and margin clearance during MMS for melanoma. CONCLUSION: Mohs micrographic surgery for melanoma is performed with varied surgical techniques. To establish best practices, additional research is necessary to determine how different techniques affect outcomes.

Consensus-Based Recommendations on the Prevention of Squamous Cell Carcinoma in Solid Organ Transplant Recipients: A Delphi Consensus Statement.

IMPORTANCE: There is a paucity of evidence to guide physicians regarding prevention strategies for cutaneous squamous cell carcinoma (CSCC) in solid organ transplant recipients (SOTRs). OBJECTIVE: To examine the development and results of a Delphi process initiated to identify consensus-based medical management recommendations for prevention of CSCC in SOTRs. EVIDENCE REVIEW: Dermatologists with more than 5 years' experience treating SOTRs were invited to participate. A novel actinic damage and skin cancer index (AD-SCI), consisting of 6 ordinal stages corresponding to an increasing burden of actinic damage and CSCC, was used to guide survey design. Three sequential web-based surveys were administered from January 1, 2019, to December 31, 2020. Pursuant to Delphi principles, respondents thoroughly reviewed all peer responses between rounds. Supplemental questions were also asked to better understand panelists' rationale for their responses. FINDINGS: The Delphi panel comprised 48 dermatologists. Respondents represented 13 countries, with 27 (56%) from the US. Twenty-nine respondents (60%) were Mohs surgeons. Consensus was reached with 80% or higher concordance among respondents when presented with a statement, question, or management strategy pertaining to prevention of CSCC in SOTRs. A near-consensus category of 70% to less than 80% concordance was also defined. The AD-SCI stage-based recommendations were established if consensus or near-consensus was achieved. The panel was able to make recommendations for 5 of 6 AD-SCI stages. Key recommendations include the following: cryotherapy for scattered actinic keratosis (AK); field therapy for AK when grouped in 1 anatomical area, unless AKs are thick in which case field therapy and cryotherapy were recommended; combination lesion directed and field therapy with fluorouracil for field cancerized skin; and initiation of acitretin therapy and discussion of immunosuppression reduction or modification for patients who develop multiple skin cancers at a high rate (10 CSCCs per year) or develop high-risk CSCC (defined by a tumor with approximately ≥20% risk of nodal metastasis). No consensus recommendation was achieved for SOTRs with a first low risk CSCC. CONCLUSIONS AND RELEVANCE: Physicians may consider implementation of panel recommendations for prevention of CSCC in SOTRs while awaiting high-level-of-evidence data. Additional clinical trials are needed in areas where consensus was not reached.

Preferences for Prophylactic Oral Antibiotic Use in Dermatologic Surgery: A Multicenter Discrete Choice Experiment.

BACKGROUND: Antibiotics are often prescribed after dermatologic surgery for infection prophylaxis, but patient preferences about prophylactic antibiotics are not well understood. OBJECTIVE: To understand patient preferences about taking antibiotics to prevent surgical site infection (SSI) relative to antibiotic efficacy and antibiotic-associated adverse drug reactions. MATERIALS AND METHODS: Multi-center, prospective discrete choice experiment (DCE). RESULTS: Three hundred thirty-eight respondents completed the survey and DCE. 54.8% of respondents preferred to take an antibiotic if it reduced the SSI rate from 5% to 2.5% and if the risk of adverse drug reactions was low (1% risk gastrointestinal upset, 0.5% risk itchy skin rash, 0.01% risk emergency department visit). Even if an antibiotic could eliminate SSI risk (0% risk SSI) and had a low adverse drug reaction profile, 26.7% of respondents prefer not to take prophylactic oral antibiotics. CONCLUSION: Risk-benefit thresholds for taking antibiotics to prevent SSI vary widely. Clinical trials are needed to better characterize the effectiveness and risks of oral antibiotic SSI prophylaxis to guide decision-making. Future studies should also evaluate whether shared decision-making can improve the patient experience.

Systematic review and meta-analysis of local recurrence rates of head and neck cutaneous melanomas after wide local excision, Mohs micrographic surgery, or staged excision.

BACKGROUND: Prospective trials have not compared the local recurrence rates of different excision techniques for cutaneous melanomas on the head and neck. OBJECTIVE: To determine local recurrence rates of cutaneous head and neck melanoma after wide local excision (WLE), Mohs micrographic surgery (MMS), or staged excision. METHODS: A systematic review of PubMed, EMBASE, and Web of Science identified all English case series, cohort studies, and randomized controlled trials that reported local recurrence rates after surgery for cutaneous head and neck melanoma. A meta-analysis utilizing a random effects model calculated weighted local recurrence rates and confidence intervals (CI) for each surgical technique and for subgroups of MMS and staged excision. RESULTS: Among 100 manuscripts with 13,998 head and neck cutaneous melanomas, 51.0% (7138) of melanomas were treated by WLE, 34.5% (4826) by MMS, and 14.5% (2034) by staged excision. Local recurrence rates were lowest for MMS (0.61%; 95% CI, 0.1%-1.4%), followed by staged excision (1.8%; 95% CI, 1.0%-2.9%) and WLE (7.8%; 95% CI, 6.4%-9.3%). LIMITATIONS: Definitions of local recurrence varied. Surgical techniques included varying proportions of invasive melanomas. Studies had heterogeneity. CONCLUSION: Systematic review and meta-analysis show lower local recurrence rates for cutaneous head and neck melanoma after treatment with MMS or staged excision compared to WLE.