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.

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.

Human papillomavirus and posttransplantation cutaneous squamous cell carcinoma: A multicenter, prospective cohort study.

Organ transplant recipients (OTRs) have a 100-fold increased risk of cutaneous squamous cell carcinoma (cSCC). We prospectively evaluated the association between ß genus human papillomaviruses (ßPV) and keratinocyte carcinoma in OTRs. Two OTR cohorts without cSCC were assembled: cohort 1 was transplanted in 2003-2006 (n = 274) and cohort 2 was transplanted in 1986-2002 (n = 352). Participants were followed until death or cessation of follow-up in 2016. ßPV infection was assessed in eyebrow hair by using polymerase chain reaction-based methods. ßPV IgG seroresponses were determined with multiplex serology. A competing risk model with delayed entry was used to estimate cumulative incidence of histologically proven cSCC and the effect of ßPV by using a multivariable Cox regression model. Results are reported as adjusted hazard ratios (HRs). OTRs with 5 or more different ßPV types in eyebrow hair had 1.7 times the risk of cSCC vs OTRs with 0 to 4 different types (HR 1.7, 95% confidence interval 1.1-2.6). A similar risk was seen with high ßPV loads (HR 1.8, 95% confidence interval 1.2-2.8). No significant associations were seen between serum antibodies and cSCC or between ßPV and basal cell carcinoma. The diversity and load of ßPV types in eyebrow hair are associated with cSCC risk in OTRs, providing evidence that ßPV is associated with cSCC carcinogenesis and may present a target for future preventive strategies.

Metastasis Risk of Cutaneous Squamous Cell Carcinoma in Organ Transplant Recipients and Immunocompetent Patients.

Organ transplant recipients (OTRs) have a high incidence of cutaneous squamous cell carcinoma (cSCC), and immunosuppression has been reported to be an important risk factor for metastasis. The aim of this study was to identify the metastasis risk over a 10-year period for 593 patients with cSCC, of whom 134 were OTR and 459 were immunocompetent. Metastasis incidence rate was 1,046 (95% confidence interval (95% CI) 524-2,096) per 100,000 person years in OTR and 656 (95% CI; 388-1,107) in immunocompetent patients, yielding an incidence rate ratio of 1.6 (95% CI 0.67-3.81). In OTRs head/neck location, older age at transplantation and older age at diagnosis of first cSCC were associated with metastatic risk, and 7 out of 8 metastasized tumours were smaller than 2 cm. In immunocompetent patients tumour size and tumour depth were associated with metastasis. In conclusion, we were not able to demonstrate an increased incidence rate of metastasis in OTRs compared with immunocompetent patients. However, OTRs and immunocompetent patients differed with regard to risk factors for metastasis.

p16 immunostaining in keratinocytic neoplasia in organ transplant recipients: Bowen's disease shows a characteristic pattern.

BACKGROUND: For selecting therapy, it is important to distinguish different types of keratinocytic neoplasia. It is sometimes difficult to make histopathologic diagnosis, especially in organ transplant recipients (OTR) who develop numerous lesions. METHODS: To investigate p16 immunostaining in different types of keratinocytic neoplasia in OTR, we studied 59 actinic keratoses (AK), 51 Bowen' s disease (BD), 63 squamous cell carcinomas (SCC), 16 benign keratotic lesions (BKL) from 31 OTR patients and 25 controls (eczema and psoriasis). Tissue sections were stained for H&E and p16. We scored intensity, proportion and distribution of p16 positive lesional cells. RESULTS: In 19% of AK, 92% of BD, 35% of SCC and 12% of BKL more than 15% of lesional cells were p16-positive. In 16% of AK, 80% of BD, 18% of SCC and 13% of BKL strong p16 staining was observed. BKL, AK and SCC showed focal and patchy staining, BD showed diffuse pattern with strong staining of all atypical cells. Sparing of the basal layer was predominantly seen in BD. No control specimen showed p16-overexpression. CONCLUSIONS: p16 immunostaining shows a characteristic pattern in BD, but not in AK, SCC and BKL. It appears useful in recognizing BD, but not in differentiating between other keratinocytic neoplasia.

Human Beta-papillomavirus infection and keratinocyte carcinomas.

Although the role of oncogenic human Alpha-papillomaviruses (HPVs) in the development of mucosal carcinomas at different body sites (eg cervix, anus, oropharynx) is fully recognized, a role for HPV in keratinocyte carcinomas (KCs; basal and squamous cell carcinomas) of the skin is not yet clear. KCs are the most common cancers in Caucasians, with the major risk factor being ultraviolet (UV) light exposure. A possible role for Beta-HPV types (BetaPV) in the development of KC was suggested several decades ago, supported by a number of epidemiological studies. Our current review summarizes the recent molecular and histopathological evidence in support of a causal association between BetaPV and the development of KC, and outlines the suspected synergistic effect of viral gene expression with UV radiation and immune suppression. Further insights into the molecular pathways and protein interactions used by BetaPV and the host cell is likely to extend our understanding of the role of BetaPV in KC.