Cumulative incidence and risk factors for cutaneous squamous cell carcinoma metastases in organ transplant recipients: The Skin Care in Organ Transplant Patients in Europe-International Transplant Skin Cancer Collaborative metastases study, a prospective multicenter study.

INTRODUCTION: Solid organ transplant recipients (SOTRs) are believed to have an increased risk of metastatic cutaneous squamous cell carcinoma (cSCC), but reliable data are lacking regarding the precise incidence and associated risk factors. METHODS: In a prospective cohort study, including 19 specialist dermatology outpatient clinics in 15 countries, patient and tumor characteristics were collected using standardized questionnaires when SOTRs presented with a new cSCC. After a minimum of 2 years of follow-up, relevant data for all SOTRs were collected. Cumulative incidence of metastases was calculated by the Aalen-Johansen estimator. Fine and Gray models were used to assess multiple risk factors for metastases. RESULTS: Of 514 SOTRs who presented with 623 primary cSCCs, metastases developed in 37 with a 2-year patient-based cumulative incidence of 6.2%. Risk factors for metastases included location in the head and neck area, local recurrence, size > 2 cm, clinical ulceration, poor differentiation grade, perineural invasion, and deep invasion. A high-stage tumor that is also ulcerated showed the highest risk of metastasis, with a 2-year cumulative incidence of 46.2% (31.9%-68.4%). CONCLUSIONS: SOTRs have a high risk of cSCC metastases and well-established clinical and histologic risk factors have been confirmed. High-stage, ulcerated cSCCs have the highest risk of metastasis.

Mimicking fat grafting of fibrotic scars using 3D-organotypic skin cultures.

Wound healing of deep burn injuries is often accompanied by severe scarring, such as hypertrophic scar (HTS) formation. In severe burn wounds, where the subcutis is also damaged, the scars adhere to structures underneath, resulting in stiffness of the scar and impaired motion. Over the recent years, a promising solution has emerged: autologous fat grafting, also known as lipofilling. Previous clinical reports have shown that the anti-fibrotic effect has been attributed to the presence of adipose-derived stromal cells (ADSC). In the proposed study, we aim to investigate the effect of fat grafting in 3D organotypic skin cultures mimicking an HTS-like environment. To this end, organotypic skin cultures were embedded with normal skin fibroblasts (NF) or HTS-derived fibroblasts with or without incorporation of human adipose subcutaneous tissue (ADT) and one part was thermally wounded to examine their effect on epithelialization. The developed skin cultures were analysed on morphology and protein level. Analysis revealed that ADT-containing organotypic skin cultures comprise an improved epidermal homeostasis, and a fully formed basement membrane, similar to native human skin (NHS). Furthermore, the addition of ADT significantly reduced myofibroblast presence, which indicates its anti-fibrotic effect. Finally, re-epithelialization measurements showed that ADT reduced re-epithelialization in skin cultures embedded with NFs, whereas HTS-fibroblast-embedded skin cultures showed complete wound closure. In conclusion, we succeeded in developing a 3D organotypic HTS-skin model incorporated with subcutaneous tissue that allows further investigation on the molecular mechanism of fat grafting.

Dynamic characteristics of skin reaction force in different body postures.

Mechanical stress influences scarring of a surgical wound. Several lines have been proposed for the best excision direction. It is unknown if these lines still apply when the body posture changes. The objective is to measure the skin reaction force in four directions and determine the direction of least force. Secondary objective is to determine if the reaction force varies in a different body posture. Skin reaction force was measured with the compressiometer in 30 participants on four different locations (forearm/upper arm/shoulder blade/lower back) in four directions (0°-45°-90°-135°) and two body postures. The direction of least skin reaction force changed with a different body posture and was significant for the forearm (p < 0.01) and shoulder blade (p = 0.05) The skin reaction force in all four direction changed significantly in a different body posture, except the 45° line in the upper arm and shoulder blade. Our results demonstrate that the skin reaction force in four directions in four locations varies with change in body posture. Focus should therefore not only lay on choosing the right direction, but also on managing skin tension postoperatively.

HLA expression as a risk factor for metastases of cutaneous squamous-cell carcinoma in organ- transplant recipients.

BACKGROUND: Solid organ-transplant recipients (SOTR) have an increased risk of cutaneous squamous-cell carcinoma (cSCC), metastasis and death from cSCC. In immunocompetent patients with mucosal SCC, downregulation of HLA class I is associated with poor prognosis. Since the degree of HLA expression on tumor cells could play a role in immunogenicity and pathophysiology of cSCC metastasis, we hypothesized that decreased HLA expression is associated with an increased risk of metastasis. METHODS: We compared HLA expression between primary metastasized cSCCs, their metastases, and non-metastasized cSCCs from the same patients. Samples were stained for HLA-A, HLA-B/-C and quantified by calculating the difference in immunoreactivity score (IRS) of the primary cSCC compared with all non-metastasized cSCCs. RESULTS: The mean IRS score for HLA-B/C expression was 2.07 point higher in metastasized compared to non-metastasized cSCCs (p = 0.065, 95 % CI -0.18-4.32). 83.3 % of the primary metastasized cSCCs had an IRS score of 4 or higher, compared to 42.9 % in non-metastasized cSCCs. Moderately to poorly differentiated cSCCs had more HLA class I expression compared to well-differentiated cSCCs. CONCLUSION: Contrary to immunocompetent patients, HLA-B/C expression tends to be upregulated in metastasized cSCC compared to non-metastasized cSCC in SOTR, suggesting that different tumor escape mechanisms play a role in SOTR compared to immunocompetent patients.

External Validation of the Skin and UV Neoplasia Transplant Risk Assessment Calculator (SUNTRAC) in a Large European Solid Organ Transplant Recipient Cohort.

Importance: The Skin and UV Neoplasia Transplant Risk Assessment Calculator (SUNTRAC) tool has been developed in the US to facilitate the identification of solid organ transplant recipients (SOTRs) at a higher risk of developing skin cancer. However, it has not yet been validated in populations other than the one used for its creation. Objective: To provide an external validation of the SUNTRAC tool in different SOTR populations. Design, Setting, and Participants: This retrospective external validation prognostic study used data from a prospectively collected cohort of European SOTRs from transplant centers at teaching hospitals in the Netherlands (1995-2016) and Spain (2011-2021). Participants were screened and followed up at dermatology departments. Data were analyzed from September to October 2021. Main Outcomes and Measures: The discrimination ability of the SUNTRAC tool was assessed via a competing risk survival analysis, cumulative incidence plots, and Wolbers concordance index. Calibration of the SUNTRAC tool was assessed through comparison of projected skin cancer incidences. Skin cancer diagnoses included squamous cell carcinoma, basal cell carcinoma, melanoma, and Merkel cell carcinoma. Results: A total of 3421 SOTRs (median age at transplant, 53 [quartile 1: 42; quartile 3: 62] years; 2132 [62.3%] men) were assessed, including 72 Asian patients (2.1%), 137 Black patients (4.0%), 275 Latinx patients (8.0%), 109 Middle Eastern and North African patients (3.2%), and 2828 White patients (82.7%). With a total of 23 213 years of follow-up time, 603 patients developed skin cancer. The SUNTRAC tool classified patients into 4 groups with significantly different risks of developing skin cancer during follow-up. Overall, the relative rate for developing skin cancer estimated using subdistribution hazard ratios (SHRs) and using the low-risk group as the reference group, increased according to the proposed risk group (medium-risk group: SHR, 6.8 [95% CI, 3.8-12.1]; P < .001; high-risk group: SHR, 15.9 [95% CI, 8.9-28.4]; P < .001; very-high-risk group: SHR, 54.8 [95% CI, 29.1-102.9]; P < .001), with a concordance index of 0.72. Actual skin cancer incidences were similar to those predicted by the SUNTRAC tool (5-year skin cancer cumulative incidence for medium-risk group: predicted, 6.2%; observed, 7.0%). Conclusions and Relevance: The findings of this external validation prognostic study support the use of the SUNTRAC tool in European populations for stratifying SOTRs based on their skin cancer risk and also detecting patients at a high risk of developing skin cancer. This can be helpful in prioritizing and providing better screening and surveillance for these patients.

The Compressiometer: Toward a New Skin Tensiometer for Research and Surgical Planning.

After surgery, around 35% of patients experience problems of excessive scarring, causing disfiguring and impaired function. An incision placed in the wrong direction causes unnecessary skin tension on the wound, resulting in increased collagen disposition and potentially hypertrophic scars. Currently, skin tension lines are used for incision planning. However, these lines are not universal and are a static representation of the skin tension that is in fact under influence of muscle action. By designing a new skin force measurement device the authors intend to make research on dynamic skin characteristics possible and to objectify incision planning and excision closure planning. The device applies a known compressive force to the skin in standardized directions and measures the displacement of the skin. This allows users to measure the skin reaction force in response to compression and to determine the optimal incision line or best wound closure direction. The device has an accuracy of 96% and a sensitivity of < 0.01 mm. It is compact, works non-invasively and standardizes measurement directions and is therefore an improvement over previously designed skin tensiometers.

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.

A Low-Grade Trichoblastic Carcinoma Treated with Mohs Micrographic Surgery.

Trichoblastomas are rare dermal neoplasms usually found on the scalp and face. Histology shows a proliferation of small basaloid cells arranged in cords or fields surrounded by cellular stroma. Trichoblastomas are usually not aggressive, but trichoblastic carcinomas arising from preexisting trichoblastomas have been described and have been linked to basal cell carcinoma. We found a tumor with features of trichoblastoma with presence of Merkel cells, but with a deeply infiltrative growth pattern into the fat and muscle tissue, without significant architectural or cellular atypia. Tumors with similar growth patterns were previously described as deeply invasive trichoblastic neoplasms. It appears to be a new entity that has been described before but has not been fully characterized: low-grade trichoblastic carcinoma. This malignancy seems to show only locally aggressive growth. Radical excision was accomplished with Mohs micrographic surgery.

To Tie or Not to Tie-Over Full-Thickness Skin Grafts in Dermatologic Surgery: A Systematic Review of the Literature.

BACKGROUND: Tie-over dressings are frequently used for skin grafts. Although a dressing is necessary for split-thickness skin grafts, their use in full-thickness skin grafts (FTSGs) is questionable. OBJECTIVE: This review was conducted to investigate the influence of different tie overs and dressings on graft take for FTSGs in cutaneous surgery. MATERIALS AND METHODS: An electronic database search was performed in MEDLINE, EMBASE, Web of Science, and the Cochrane library. The following search terms and comparable were used: skin transplantation, tie-over, fixation, sutures, and take. RESULTS: Fifteen articles met the inclusion criteria. Eight studies describe no use of a tie-over dressing for FTSGs. Dressing types included antibacterial dressings, foam or sponges, and bolsters. The lowest graft take was 80% (with a tie-over dressing). The highest graft take was 100% (with and without a tie-over dressing). CONCLUSION: The results show that, regardless of the technique used, the overall graft success rate is high. Although a definite recommendation could not be made, it seems that a graft without a tie-over dressing can suffice in certain circumstances.

Measuring Forces in Suture Techniques for Wound Closure.

BACKGROUND: The use of sutures remains the first choice for wound closure. However, incorrect use of a suture technique can lead to impaired healing. Many techniques are described for high-tension wounds, but not much is known about their mechanical properties. Complications of excessive tension include dehiscence, infection, and ischemic necrosis and could be prevented. This study aimed to compare forces in five techniques (single, horizontal mattress, vertical mattress, pulley, and modified pulley suture) in a standardized wound tension model. MATERIALS AND METHODS: A standardized neoprene wound model was developed on the ForceTRAP system (MediShield B.V., Delft, The Netherlands) to mimic a 5 Newton (N) wound. Five different suture techniques were each repeated 10 times by a student, resident dermatology, and dermsurgeon. The pulling force of the suture's first throw was measured with the Hook-in-Force sensor (Technical University Delft, The Netherlands). Changes in wound tension were measured by the ForceTRAP system. The ForceTRAP is a platform measuring forces from 0 to 20 N in three dimensions with an accuracy of 0.1 N. The Hook-in-Force is a force sensor measuring 0-15 N with an accuracy of 0.5 N. Maximum and mean forces were calculated for each suture technique and operator. RESULTS: Mean maximum pulling force: 5.69 N (standard deviation [SD], 0.88) single, 7.25 N (SD, 1.33) vertical mattress, 8.11 N (SD, 1.00) horizontal mattress, 3.46 N (SD, 0.61) pulley, and 4.52 N (SD, 0.67) modified pulley suture. The mean force increase on the skin (substitute) ranged between 0.80 N (pulley) and 0.96 N (vertical mattress). CONCLUSIONS: The pulley suture requires less pulling force compared with other techniques. The mechanical properties of sutures should be taken in consideration when choosing a technique to close wounds.

Incomplete Excision of Cutaneous Squamous Cell Carcinoma; Systematic Review of the Literature.

The treatment of choice for cutaneous squamous cell carcinoma is complete surgical excision. Incomplete excision of cutaneous squamous cell carcinoma has an increased risk of local recurrence, deep subclinical progression, and metastasis. This study aimed to investigate the proportion and risk factors of incomplete excised cutaneous squamous cell carcinoma. A systematic review of the literature was performed. Incomplete excision rates for cutaneous squamous cell carcinoma ranged from 0.4% to 35.7%. The pooled incomplete excision risk estimate was 13% (95% confidence interval 9-17%). Risk factors noted in more than one study for incomplete excision included tumor depth and size, type of operator, head and neck localization, and former incomplete excision. We found an overall incomplete excision rate of 13% for cutaneous squamous cell carcinoma. Risk factors should be taken into account in the management of cutaneous squamous cell carcinoma surgical treatment.

Tissue-sparing properties of Mohs micrographic surgery for infiltrative basal cell carcinoma.

BACKGROUND: Mohs micrographic surgery (MMS) should lead to tissue sparing of healthy skin compared with standard surgical excision because smaller surgical margins are used. OBJECTIVE: To quantify the tissue-sparing properties of MMS in primary basal cell carcinoma (BCC) with an infiltrative growth pattern. METHODS: A prospective study including 256 primary BCCs with an infiltrative growth pattern was performed. Tumor sizes were measured in 2 perpendicular directions. Surface defect areas after MMS were measured. The suspected defect surface area with standard excision using a 5-mm margin was calculated. The primary outcome of this study was the size of the defect surface area spared with MMS compared with the calculated defect surface area with a standard excision. RESULTS: The median tumor size was 71 mm2, and the median defect size after MMS was 154 mm2. The median defect size calculated for standard surgical excision was 298 mm2. We have shown that MMS of BCC with an infiltrative growth pattern had a 46.4% tissue-sparing effect when compared with standard surgical excision (95% confidence interval, 43.4%-49.1%; P value < .001). LIMITATIONS: Single-center study design. Lack of a randomized control group for ethical reasons. CONCLUSION: A rate of tissue sparing of 46% can be reached by using MMS for primary BCC with an infiltrative growth pattern.

Safety Studies in the Field of Liposuction: A Systematic Review.

BACKGROUND: There is an increasing demand for safety standards for cosmetic treatments. With regard to liposuction, interdisciplinary consensus is lacking, especially regarding treatment setting and physician specialty. OBJECTIVE: A solid, independent interpretation of scientific data on safety requires a systematic approach, which is the aim of this study. METHODS: A systematic literature search was conducted for safety studies about liposuction through April 2017. Fatalities and/or reported serious adverse events served as outcome measures for safety. RESULTS: Twenty-four studies were included. Factors that contributed to increased serious complication and mortality risk were: use of the (super)wet technique; use of systemic anesthetics, especially general anesthesia and intravenous sedation; execution by a plastic surgeon; execution in an operating room; and combination with other procedures. CONCLUSION: Liposuction using tumescent local anesthesia has been shown to be the safest method of fat removal, especially if no or only minimal systemic anesthesia is used. Performance of this technique in an office-based setting has been proven to be safe beyond doubt. When systemic anesthesia is used, an outpatient or ambulatory surgery facility seems also safe. Regardless of the physician specialty, knowledge and training on the execution of the tumescent procedure are vital to ensure optimal safety.