Application expansion of small intestinal submucosa extracellular matrix in complex and surgical wounds.

A wound is hard-to-heal or complex when the defect fails to progress through the normal stages of wound healing in a timely fashion. Hard-to-heal wounds such as diabetic foot or venous leg ulcers can be long-lasting conditions. Alternatively, complex acute wounds that occur from trauma, burns, postoperative, necrosis and some dermatological diseases can also result in hard-to-heal wounds. This article reviews important considerations in the management of complex acute wounds, such as time to wound closure, pain, scarring, patient satisfaction and identification of options that can promote healing of grafts and flaps, while reducing donor-site morbidity. Primary research has demonstrated the inherent benefits of small intestinal submucosa extracellular matrix (SIS-ECM), a naturally occurring porcine matrix that promotes development of dermis-like tissue in both complex acute and hard-to-heal wounds. Presently, the literature provides mostly case studies demonstrating the benefits of SIS-ECM in the management of complex acute wounds. The available case series suggest emerging clinical benefits including rapid time to coverage, avoidance of donor-site complications and development of granulation tissue in locations of low circulation, which improves poor graft sites, potentially reducing dehiscence and providing support for reconstruction flaps and grafts.

Enhanced metastatic risk assessment in cutaneous squamous cell carcinoma with the 40-gene expression profile test.

Aim: To clinically validate the 40-gene expression profile (40-GEP) test for cutaneous squamous cell carcinoma patients and evaluate coupling the test with individual clinicopathologic risk factor-based assessment methods. Patients & methods: In a 33-site study, primary tumors with known patient outcomes were assessed under clinical testing conditions (n = 420). The 40-GEP results were integrated with clinicopathologic risk factors. Kaplan-Meier and Cox regression analyses were performed for metastasis. Results: The 40-GEP test demonstrated significant prognostic value. Risk classification was improved via integration of 40-GEP results with clinicopathologic risk factor-based assessment, with metastasis rates near the general cutaneous squamous cell carcinoma population for class 1 and ≥50% for class 2B. Conclusion: Combining molecular profiling with clinicopathologic risk factor assessment enhances stratification of cutaneous squamous cell carcinoma patients and may inform decision-making for risk-appropriate management strategies.

Plain language summary Cutaneous squamous cell carcinoma is a common skin cancer, with approximately 2 million cases diagnosed each year in the USA. Because substantial numbers of patients experience metastasis, which can result in death, accurate metastatic risk assessment is important. Clinicians use clinicopathologic factors to determine risk for disease progression. However, traditional methods miss pinpointing many patients who experience metastasis and sometimes categorize patients as at risk who do not develop metastasis, indicating that additional tools are needed. A molecular test, the 40-gene expression profile (40-GEP), was developed to predict metastatic risk based on the biology of the tumor. This study demonstrates that the 40-GEP, either as an independent tool or together with traditional methods, accurately identifies patients' risk of metastasis. Using the 40-GEP could improve patient management to improve patient outcomes.

Is There a Smoking Gun for Nicotine? A Review of the Role of Nicotine in Dermatologic Surgery.

BACKGROUND: Dermatologic surgeons are faced with a dilemma when counseling actively smoking patients who require dermatologic surgery: recommend total cessation of all nicotine that is associated with extremely high rates of cessation failure or recommend nicotine replacement therapy (NRT). OBJECTIVE: To determine the safety of NRT in dermatologic surgery. MATERIALS AND METHODS: PubMed was queried: [(nicotine OR electronic cigarettes) AND (flap OR wound healing)]. RESULTS: Smoking tobacco is detrimental to wound healing, supported by ample evidence (1A). Perioperative smoking cessation reduces risk (1B). Basic science demonstrates both a benefit and detriment of nicotine depending on the factor studied (2A). Human studies suggest no detrimental effect of nicotine on perioperative complications (1B). Nicotine may be detrimental to flaps, but evidence is limited to basic science (2A). CONCLUSION: Dermatologists should consider recommending nicotine replacement for smokers in the perioperative period. Evidence is lacking to determine safety in flaps. It is presumed based on animal studies that nicotine has a negative effect on flaps; however, it is likely less than tobacco. Weighing the risk of cessation failure without nicotine replacement versus nicotine replacement after flap is challenging. Electronic cigarettes should be discouraged as a means of NRT.

Analysis of Factors Contributing to Perioperative Mohs Micrographic Surgery Anxiety: Patient Survey Study at an Academic Center.

BACKGROUND: High perioperative patient anxiety is predictive of worse postoperative pain and quality of life. Several Mohs micrographic surgery (MMS) patient characteristics influence anxiety; however, the contributions of certain factors remain uncertain. OBJECTIVE: Investigate factors influencing perioperative MMS patient anxiety, especially those with debated impact or unclear data. METHODS: The authors surveyed 145 adult patients receiving MMS performed by a single MMS surgeon from 2018 to 2020. Patients self-reported demographics, history, and 10-point visual analog scale anxiety assessments at multiple stages. Health care provider (HCP)-perceived anxiety assessments were queried. A stepwise multiple regression modeling approach was used to explore potential factors. RESULTS: Younger age, female sex, and a self-reported history of anxiety confirmed by prior HCP diagnosis were significant predictors of pre-MMS anxiety. Postoperative anxiety increased with more layers removed and higher pre-MMS anxiety. HCP-perceived patient anxiety increased with younger patient age, more layers removed, prior skin cancer removal, and HCP-perceived pre-MMS patient anxiety. CONCLUSION: Anxiety-reducing interventions should target young female patients with a history of HCP-diagnosed anxiety, and patients with more layers removed. Prior skin cancer removal is associated with increased HCP-perceived intraoperative patient anxiety; however, it is not significant for patient-reported anxiety. Pre-MMS consultation may not be effective for anxiety reduction.

Validation of a 40-gene expression profile test to predict metastatic risk in localized high-risk cutaneous squamous cell carcinoma.

BACKGROUND: Current staging systems for cutaneous squamous cell carcinoma (cSCC) have limited positive predictive value for identifying patients who will experience metastasis. OBJECTIVE: To develop and validate a gene expression profile (GEP) test for predicting risk for metastasis in localized, high-risk cSCC with the goal of improving risk-directed patient management. METHODS: Archival formalin-fixed paraffin-embedded primary cSCC tissue and clinicopathologic data (n = 586) were collected from 23 independent centers in a prospectively designed study. A GEP signature was developed using a discovery cohort (n = 202) and validated in a separate, nonoverlapping, independent cohort (n = 324). RESULTS: A prognostic 40-GEP test was developed and validated, stratifying patients with high-risk cSCC into classes based on metastasis risk: class 1 (low risk), class 2A (high risk), and class 2B (highest risk). For the validation cohort, 3-year metastasis-free survival rates were 91.4%, 80.6%, and 44.0%, respectively. A positive predictive value of 60% was achieved for the highest-risk group (class 2B), an improvement over staging systems, and negative predictive value, sensitivity, and specificity were comparable to staging systems. LIMITATIONS: Potential understaging of cases could affect metastasis rate accuracy. CONCLUSION: The 40-GEP test is an independent predictor of metastatic risk that can complement current staging systems for patients with high-risk cSCC.

Assessment of Functionality in Elderly Patients When Determining Appropriate Treatment for Nonmelanoma Skin Cancers.

BACKGROUND: The treatment of nonmelanoma skin cancer (NMSC) in the elderly population is a source of significant debate. Mohs micrographic surgery (MMS) is a highly effective treatment option yet not every patient with a cutaneous malignancy that meets appropriate use criteria (AUC) should be treated with surgery. OBJECTIVE: The purpose of this study was to use the Karnofsky Performance Status (KPS) scale to categorize the functional status of patients aged 75 years and older who required treatment of NMSC. The authors wanted to see whether functionality played a role on the treatment selection. METHODS: Patients aged 75 years and older presenting for biopsy of a suspected NMSC that met AUC for MMS were included in the study. Trained medical assistants used the KPS scale to assess patient functionality. Treatment modality was recorded once the biopsy confirmed the NMSC. RESULTS: A cohort of 203 subjects met inclusion criteria for the study. There was a statistically significant difference in utilization of surgical treatments between high and low functionality patients (p = .03). CONCLUSION: Dermatologists consider patient functionality when selecting a treatment for NMSC and use less invasive modalities for patients with poor functional status, even when the tumor meets AUC.

Sebaceous carcinoma: evidence-based clinical practice guidelines.

Sebaceous carcinoma usually occurs in adults older than 60 years, on the eyelid, head and neck, and trunk. In this Review, we present clinical care recommendations for sebaceous carcinoma, which were developed as a result of an expert panel evaluation of the findings of a systematic review. Key conclusions were drawn and recommendations made for diagnosis, first-line treatment, radiotherapy, and post-treatment care. For diagnosis, we concluded that deep biopsy is often required; furthermore, differential diagnoses that mimic the condition can be excluded with special histological stains. For treatment, the recommended first-line therapy is surgical removal, followed by margin assessment of the peripheral and deep tissue edges; conjunctival mapping biopsies can facilitate surgical planning. Radiotherapy can be considered for cases with nerve or lymph node involvement, and as the primary treatment in patients who are ineligible for surgery. Post-treatment clinical examination should occur every 6 months for at least 3 years. No specific systemic therapies for advanced disease can be recommended, but targeted therapies and immunotherapies are being developed.

Correlation Between Original Biopsy Pathology and Mohs Intraoperative Pathology.

BACKGROUND: The pathology observed on initial biopsy specimens for nonmelanoma skin cancer (NMSC), specifically the tumor subtype, weighs heavily into the selection of the treatment modality. Recognizing aggressive features on intraoperative Mohs micrographic surgery (MMS) frozen sections that were not indicated on initial biopsy reports is not uncommon. To date, there is limited data describing this discrepancy. OBJECTIVE: To investigate the frequency and nature of incongruity between the pathology seen in initial biopsies and intraoperative Mohs sections, providing information that will potentially impact skin cancer treatment and biopsy recommendations. METHODS: Retrospective chart review of cases of NMSC referred for MMS at the authors' institution over a 1-year period, recording changes between tumor subtypes observed at biopsy and those observed during MMS. RESULTS: Cases (50.5%) (n = 163) changed aggressiveness. Of these, 33% (n = 108) were more aggressive, whereas 17% (n = 55) were less aggressive. CONCLUSION: A substantial discrepancy was observed between preoperative biopsy and intraoperative pathology, including a significant portion tumors that became more aggressive. These results suggest that treatment modalities without margin control may not provide adequate treatment for a considerable number of NMSC based on preoperative tumor type alone.