High-throughput lipidomic profiles sampled with electroporation-based biopsy differentiate healthy skin, cutaneous squamous cell carcinoma, and basal cell carcinoma.

BACKGROUND: The incidence rates of cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC) skin cancers are rising, while the current diagnostic process is time-consuming. We describe the development of a novel approach to high-throughput sampling of tissue lipids using electroporation-based biopsy, termed e-biopsy. We report on the ability of the e-biopsy technique to harvest large amounts of lipids from human skin samples. MATERIALS AND METHODS: Here, 168 lipids were reliably identified from 12 patients providing a total of 13 samples. The extracted lipids were profiled with ultra-performance liquid chromatography and tandem mass spectrometry (UPLC-MS-MS) providing cSCC, BCC, and healthy skin lipidomic profiles. RESULTS: Comparative analysis identified 27 differentially expressed lipids (p < 0.05). The general profile trend is low diglycerides in both cSCC and BCC, high phospholipids in BCC, and high lyso-phospholipids in cSCC compared to healthy skin tissue samples. CONCLUSION: The results contribute to the growing body of knowledge that can potentially lead to novel insights into these skin cancers and demonstrate the potential of the e-biopsy technique for the analysis of lipidomic profiles of human skin tissues.

Transmission of Genetic Material and Malignant Cells of Cutaneous Origin via Surgical Sutures.

BACKGROUND: Seeding of skin cancer cells following diagnostic or therapeutic surgical procedures can occur and might cause local recurrences. As current preferred therapy for skin malignancy is surgical excision, seeding of tumour cells by manipulating malignant tissue or suturing can be another factor leading to recurrences. OBJECTIVE: To evaluate whether genetic material and malignant cells adhere to standard suture materials. METHODS: This prospective study included patients who underwent excision of skin lesions. Monofilament and braided sutures were examined. Sutures were passed through the observed tumour or healthy skin margins and were examined for DNA material and cells by cytological analysis, cell culture and characterization, and DNA analysis. RESULTS: Twenty-two patients and 148 sutures were included. DNA quantification showed DNA material on all sutures, with no significant difference between braided and monofilament sutures. Cytological analysis showed that all slides prepared from cell blocks contained normal squamous and atypical cells. Cell culture and characterization showed viable cells adhering to the sutures under direct light microscopy. Cell cultures showed rapid proliferation of epithelial cells from squamous cell carcinoma specimens. CONCLUSION: Suture materials carry DNA material and cells, including malignant cells of cutaneous origin and may seed them at distant sites.

The Mastoid Skin Graft: A Fast, Efficient Donor Site for Auricle Reconstruction After Mohs Surgery.

BACKGROUND: Mohs micrographic surgery has been considered the gold standard for treating nonmelanoma skin cancers. Approximately 8% to 10% of skin cancers requiring Mohs surgery occur on the auricle. Skin grafts can be used to achieve optimal functional and cosmetic results. OBJECTIVES: To describe a skin graft technique using the mastoid area as a donor site for auricular reconstruction following Mohs micrographic surgery, to achieve optimal esthetic results in functionally important areas. METHODS: This retrospective study assessed the outcomes of patients who underwent MMS in an out-patient Mohs surgery clinic from 2010 to 2021. All patients had MMS of the auricle with reconstruction using a split thickness skin graft harvested from the mastoid area. RESULTS: A total of 154 patients were included. The average lesion diameter was 13.7 mm (range 5-30 mm), excised in an average of 1.9 rounds of MMS. Skin graft success rate was 96%. Complications included one patient with a hypertrophic scar. The cosmetic appearance of the recipient site was rated as excellent by 87.5% of patients. All patients rated the cosmetic appearance of the donor area as excellent and well-concealed. CONCLUSIONS: Split thickness skin grafts harvested from the mastoid area are a quick and efficient reconstruction method for post-Mohs auricular defects.

αvß3 Integrin as a Link between the Development of Fibrosis and Thyroid Hormones in Systemic Sclerosis.

Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of the skin and internal organs. Key players mediating fibrosis are myofibroblasts (MF) that, following transforming growth factor ß (TGFß) exposure, produce a collagen-rich extracellular matrix (ECM) that induces myofibroblast differentiation. Myofibroblasts express αvß3 integrin (a membrane receptor for thyroid hormones) and miRNA-21 that promotes deiodinase-type-3 expression (D3), causing the degradation of triiodothyronine (T3) that attenuates fibrosis. We hypothesized that αvß3 affects the fibrotic processes through its thyroid hormones (THs) binding site. To test this, dermal fibroblasts (DF) were cultured with/without TGFß and removed with a base, leaving only normal/fibrotic ECMs in wells. Then, DF were cultured on the ECMs with/without tetrac (αvß3 ligand, T4 antagonist), and evaluated for pro-fibrotic characteristics, αvß3, miRNA-21, and D3 levels. Blood free-T3 (fT3), miRNA-21 levels, and the modified Rodnan skin score (MRSS) were evaluated in SSc patients. We found that the "fibrotic-ECM" significantly increased the pro-fibrotic characteristics of DF and the levels of miRNA-21, D3, and αvß3, compared to the "normal-ECM." Tetrac significantly inhibited the effects of the "fibrotic-ECM" on the cells. In accordance with tetrac's effect on D3/miRNA-21, a negative correlation was found between the patients' fT3 to miRNA-21 levels, and to the development of pulmonary arterial hypertension (PAH). We conclude that occupying the THs binding site of αvß3 may delay the development of fibrosis.

Predicting Mohs surgery complexity by applying machine learning to patient demographics and tumor characteristics.

Mohs micrographic surgery (MMS) is considered the gold standard for difficult-to-treat malignant skin tumors, whose incidence is on the rise. Currently, there are no agreed upon classifiers to predict complex MMS procedures. Such classifiers could enable better patient scheduling, reduce staff burnout and improve patient education. Our goal was to create an accessible and interpretable classifier(s) that would predict complex MMS procedures. A retrospective study applying machine learning models to a dataset of 8644 MMS procedures to predict complex wound reconstruction and number of MMS procedure stages. Each procedure record contained preoperative data on patient demographics, estimated clinical tumor size prior to surgery (mean diameter), tumor characteristics and tumor location, and postoperative procedure outcomes included the wound reconstruction technique and the number of MMS stages performed in order to achieve tumor-free margins. For the number of stages complexity classification model, the area under the receiver operating characteristic curve (AUROC) was 0.79 (good performance), with model accuracy of 77%, sensitivity of 71%, specificity of 77%, positive prediction value (PPV) of 14% and negative prediction value (NPV) of 98%. The results for the wound reconstruction complexity classification model were 0.84 for the AUROC (excellent performance), with model accuracy of 75%, sensitivity of 72%, specificity of 76%, PPV of 39% and NPV of 93%. The ML models we created predict the complexity of the components that comprise the MMS procedure. Using the accessible and interpretable tool we provide online, clinicians can improve the management and well-being of their patients. Study limitation is that models are based on data generated from a single surgeon.

Evaluation of Pain After Mohs Micrographic Surgery: A Prospective Study.

BACKGROUND: Mohs micrographic surgery (MMS) is a widely used technique for removal of cutaneous tumors. The procedure is well-tolerated with little surgical or postoperative pain. OBJECTIVE: This study examined pain levels after Mohs surgery throughout the first week of recovery and the relation to patient demographics, lesion characteristics, surgery details, and postoperative analgesia. METHODS: A 2-year prospective observational study included patients who underwent MMS. Patients rated the severity of postoperative pain once daily until removal of sutures and documented analgesics used. Analyses of patient and lesion characteristics along with reconstruction methods were conducted. RESULTS: A total of 2,178 patients were included in the study. Pain levels were strongest on the first postoperative day (POD) and were significantly different between genders on POD 3. Site of skin lesion, method of reconstruction, and number of stages of MMS were significantly related to postoperative pain levels on univariate and multivariate analyses. Postoperative consumption of analgesics differed significantly between men and women and was not correlated to age. CONCLUSION: Mohs surgery is generally nonpainful and is well-tolerated by men and women across all ages. The site of the lesion and method of reconstruction are the major determinants affecting the perception of pain.

Evolution of the Septal Extension Graft in Endonasal Rhinoplasty: Long-term Efficacy and Reliability.

BACKGROUND: Proper nasal tip projection and rotation have a strong impact on nasal aesthetics. Septal extension graft (SEG) is one of the tools employed to improve tip projection and rotation when performing rhinoplasty. This graft typically overlaps the existing caudal septum in the midline position, lengthening it and facilitating the repositioning of the tip. OBJECTIVES: The authors sought to describe the technical evolution of the SEG in endonasal rhinoplasty and evaluate the reliability and long-term efficacy of the current technique. METHODS: The authors evaluated presurgical and postsurgical photographs of the nasolabial angle and nasal proportions in 60 patients who underwent endonasal rhinoplasty with SEG. RESULTS: The study demonstrated a clear improvement in tip projection and rotation at the 1-year follow-up. The mean preoperative nasolabial angle was 93.75°â€…±â€…9.45° compared with 101.1°â€…±â€…5.3° following surgery. Although both were normally distributed, the range of the postoperative nasolabial angle was narrower than 1-year preoperatively (standard deviation = 5.3° vs 9.45°, respectively). The Crumley ratio, utilized to describe nasal proportions, presented significant changes in nasal proportions: 3.84 preoperatively and 4.04 postoperatively (95% confidence interval = -0.24 to -0.149; P < 0.001). CONCLUSIONS: The utilization of SEG in endonasal rhinoplasty has significantly changed since first described in 2006. The adaptations made to this technique render it more reliable, and our study demonstrates its efficacy in improving tip projection and rotation over the long-term.

Bromelain-based enzymatic debridement of chronic wounds: Results of a multicentre randomized controlled trial.

Chronic wounds are estimated to affect over 6 million people annually in the United States with an estimated annual cost of $25 billion. Debridement represents a key step in their management and is considered a basic necessity to induce the functional process of tissue repair. However, there is an unmet need for an efficient rapid acting non-surgical debridement agent. Bromelain-based enzymatic debridement has been proven to provide an effective, selective and safe non-surgical debridement in deep burns. EscharEx (MediWound Ltd, Yavne, Israel), is a bromelain-based enzymatic debridement agent currently in development for chronic wounds. The aim of this study was to assess its safety and efficacy in chronic wounds. Seventy-three patients suffering from a lower extremity ulcer of diabetic/venous insufficiency/post-surgical/traumatic aetiology were enrolled in a multicentre, assessor blinded, randomized controlled trial. Patients were randomized to topical treatment by either EscharEx or its gel vehicle for up to 10 daily 4 hour applications, and then continued follow-up for up to 6 months. The EscharEx arm achieved a significantly higher incidence of complete debridement compared to the gel vehicle arm; 55 versus 29% (p = .047), thus meeting the primary endpoint of this study. The EscharEx and gel vehicle arms achieved similar reductions in wound area, non-viable tissue area and wound healing scores during the debridement period. There were no significant differences between the arms in the incidence of complete wound closure (41% in the EsxcharEx arm vs. 53% in the gel vehicle arm) and in the mean time to complete wound closure (70.0 ± 32.8 days in the EsxcharEx arm vs. 65.7 ± 38.4 days in gel vehicle arm). There were no significant safety issues and EscharEx demonstrated a favourable benefit to risk profile.

Safety of Premedication with Oral Midazolam before Rhinoplasty as Indicated by Intraoperative Levels of Blood Oxygen Saturation.

BACKGROUND: The use of oral midazolam as premedication to induce anxiolysis before surgical procedures under local anesthesia is widely accepted in plastic surgery. Rhinoplasty performed under local anesthesia is known to generate high levels of perioperative anxiety, thus the use of appropriate premedication is important. Oral midazolam has been shown to be safe in various procedures. However, the safety of oral midazolam before rhinoplasty has not been evaluated. OBJECTIVES: To evaluate the safety of premedication with oral midazolam prior to rhinoplasty by analyzing the intraoperative blood oxygen saturation levels as predictors of adverse respiratory events. METHODS: We retrospectively reviewed the anesthesia records of 62 patients who underwent rhinoplasty under local anesthesia and received premedication with oral midazolam for anxiolysis between March 2017 and December 2017. The median age of the patients was 25.4 years, and they were all classified as American Society of Anesthesiologists class 1. The patients received 10 mg midazolam hydrochloride orally 1 hour prior to the procedure. Oxygen blood saturation was monitored using a pulse oximeter and recorded every 15 minutes. RESULTS: All the patients maintained blood oxygen saturation levels above 95% (median peripheral capillary oxygen saturation 99%) on room air, and they did not require supplemental intraoperative oxygen. There were no transient hypoxemic events during and following the procedure. CONCLUSIONS: Our study confirmed the safety of oral midazolam premedication to reduce perioperative anxiety when performing rhinoplasty under local anesthesia.

Head and Neck Cutaneous Squamous Cell Carcinoma Clinicopathological Risk Factors according to Age and Gender: A Population-based Study.

BACKGROUND: Clinicopathological risk factors for cutaneous squamous cell carcinoma of the head and neck (CSCCHN) are associated with local recurrence and metastasis. OBJECTIVES: To compare the incidence and risk factors of CSCCHN by age and gender in order to help refine the clinical evaluation and treatment process. METHODS: Clinical and pathological data of all patients diagnosed with CSCCHN during 2009-2011 were obtained from a central pathology laboratory in Israel. Estimated incidence rate calculation was standardized to the 2010 Israeli population. Independent risk factors for poorly differentiated CSCCHN were analyzed using logistic regression. RESULTS: CSCCHN was diagnosed in 621 patients. Mean age was 75.2 years; mean tumor horizontal diameter was 11.1 ± 6.8 mm. The overall estimated incidence rate in males was higher than in females (106.2 vs. 54.3 per 1,000,000, P 0.001). Twenty cases (3.2%) had poorly differentiated CSCCHN. Scalp and ear anatomic locations were observed more often in males than in females (22.1% vs. 6.1% and 20.3% vs. 3.3%, respectively, P < 0.001). Per 1 mm increment, tumor horizontal diameter increased the risk for poorly differentiated CSCCHN by 6.7% (95% CI 1.3-12.4%, P = 0.014). CONCLUSIONS: CSCCHN clinicopathological risk factors are not distributed evenly among different age and gender groups.

Electroporation-Based Biopsy Treatment Planning with Numerical Models and Tissue Phantoms.

Molecular sampling with vacuum-assisted tissue electroporation is a novel, minimally invasive method for molecular profiling of solid lesions. In this paper, we report on the design of the battery-powered pulsed electric field generator and electrode configuration for an electroporation-based molecular sampling device for skin cancer diagnostics. Using numerical models of skin electroporation corroborated by the potato tissue phantom model, we show that the electroporated tissue volume, which is the maximum volume for biomarker sampling, strongly depends on the electrode's geometry, needle electrode skin penetration depths, and the applied pulsed electric field protocol. In addition, using excised human basal cell carcinoma (BCC) tissues, we show that diffusion of proteins out of human BCC tissues into water strongly depends on the strength of the applied electric field and on the time after the field application. The developed numerical simulations, confirmed by experiments in potato tissue phantoms and excised human cancer lesions, provide essential tools for the development of electroporation-based molecular markers sampling devices for personalized skin cancer diagnostics.

Treating scars after burns with pulsed electric fields in the rat model.

Reducing scar size after severe burn injuries is an important and challenging medical, technology and social problem. We have developed a battery-powered pulsed electric field (PEF) device and surface needle electrode applicator to deliver pulsed electric fields to the healing dorsal burn wound in rats. PEF was used to treat residual burn wounds caused by metal contact in rats starting 10 days after the injury for 4 months every 11 or 22 days for 4 months using varying time applied voltages at 250-350V range, 400mA current, 40 pulses, 70 µs duration each, delivered at pulse repetition frequency 10 Hz at 5 locations inside the wound. We found 40-45% reduction in the scar size in comparison with untreated controls in both upper and lower dorsal locations on rats' backs two months after the last PEF application. We have not detected significant histopathological differences in the center of the scars besides the thickness of the newly generated epidermis, which was thicker in the PEF treated group.We showed that minimally invasively applied pulsed electric fields through needle electrodes are effective method and device for treating residual burn wounds in the rat model, reducing the size of the resulting scars, without any adverse reaction.

Safety and tolerability of a focused ultrasound device for treatment of adipose tissue in subjects undergoing abdominoplasty: a placebo-control pilot study.

BACKGROUND: High-intensity focused ultrasound (HIFU) lipolysis is a noninvasive alternative to existing surgical body-sculpting methods. OBJECTIVE: To evaluate the safety, tolerability, and histologic outcome of HIFU lipolysis using a novel device in human subjects. METHODS AND MATERIALS: In a single-blind pilot study, six healthy subjects scheduled to undergo abdominoplasty within 4 weeks received HIFU lipolysis on one side of the umbilicus. An identical placebo treatment was given to the contralateral side. Patient evaluation of complications, blood tests, and urine analysis were performed 1, 3, 7, 14, and 28 days after treatment. Excised tissue from the treated areas was sent for histologic review. RESULTS: Treatment was well tolerated. Average visual analogue pain scale scores were 3.5 ± 2.3 (range 1-7) and 0.17 ± 0.41 (range 0-1). No major adverse events were documented, and laboratory analysis after HIFU lipolysis was normal. Fat necrosis with infiltration of lymphocytes and macrophages without adjacent tissue damage was documented on histology 2 to 4 weeks after HIFU lipolysis. Damage extent correlated with size of the area treated. No pathologic findings were found on the control side. CONCLUSIONS: High-intensity focused ultrasound treatment was well tolerated and safe. Focal damage to target tissue was documented, with adjacent tissues remaining intact.

An intervention study to reduce the loss of pathology specimens.

BACKGROUND: loss of an excised lesion can have devastating clinical and legal consequences. Previously, the incidence of pathological specimen loss was 1/1466 (0.07%) due to failure to place pathology specimens in correctly labeled containers. We theorized that a strict protocol for handling specimens would help reduce losses. OBJECTIVES: To devise a protocol to reduce the loss of pathology specimens. METHODS: In this study, 7105 specimens excised by one plastic surgeon were sent to the pathology laboratory using a strict protocol, which included: using a carefully labeled specimen container, inserting the specimen into the container immediately after excision (not at the end of the procedure), positioning the specimen container close to the surgical field during the surgery, and both the nurse and surgeon signing their names on the container at the end of the procedure to confirm the contents and labeling. RESULTS: One Mohs specimen was accidentally thrown away by a pathology laboratory technician after the frozen section report was written (an incidence of 1/7105, 0.00014%). All specimens arrived at the pathology department and no lesions were lost in the operating room. CONCLUSIONS: A strict written protocol for specimen handling significantly reduces loss of pathology specimens.

A novel short-scar breast reduction technique in large breasts.

BACKGROUND: Short-scar breast reduction techniques have become very popular in the last two decades. These techniques cannot be used very often in patients with exceptionally large breasts because of the excessive amounts of redundant skin. In this article we describe our new approach for dealing with the extra skin remaining in patients with very large breasts so that they may also benefit from the short-scar breast reduction procedure. METHODS: In our technique the vertical suture line is divided into two separate suture lines. The first suture line follows the natural curve of the lower pole of the breast from the nipple to the chest wall. This line is elongated by elevating and anchoring the new inframammary fold higher on the chest wall with a suspensory suture and the skin is then closed in a straight line. The second suture line attaches the extra lower skin by closing the dermis to the chest wall and then closing the skin with a purse-string suture. This technique helps to deal with the extra skin resulting from the short-scar breast reduction technique. RESULTS: The technique was used in ten patients with large breasts. Patient satisfaction was excellent and there was no increase in complications. The technique also helped to obliterate the dead space beneath the breast and reduced seroma formation. CONCLUSION: We found that this new technique can be used safely and effectively in selected patients with large breasts without any increase in complications. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Prevalence of Skin Cancer among Beachgoers in Israel.

We assessed the prevalence of suspected skin lesions among beachgoers with dermatoscopy and evaluated their compliance with recommendations. This was conducted as a screening activity at a beach in central Israel. A dermatoscopy specialist evaluated beachgoers and maintained follow-up with them to ascertain compliance with recommendations. In all, 296 participants were screened. Normal examination was observed in 251 (85%), while a malignant finding was suspected in 12 (4%). Compliance with recommendations for excision was moderately low, with 8 of the 14 patients complying with recommendations. Skin malignancy is prevalent in local beachgoing population. Voluntary projects increase awareness in youngsters and deliver accessible screening to the older population. We believe that screening activities must be increased due to high attendance, yet close follow-up must be maintained due to intermediate compliance with medical recommendations.

Dermatoscopy as an Aid for Detecting Tumor Borders During Mohs Surgery.

Mohs micrographic surgery (MMS) is a widely used technique for removing cutaneous tumors. Currently, there is no accepted protocol to evaluate and determine lesion borders prior to surgery. Our aim was to evaluate the use of dermatoscopy as an aid for identifying lesion borders prior to MMS. Clinical and dermatoscopic images of skin lesions were evaluated by plastic surgery specialists and students to assess whether they were completely excised, the number of stages required, and characteristics of the lesions. A total of 133 patients and 2128 photographs were included in the study. Overall, specialists were better than students in evaluating lesion borders dermatoscopically (P < 0.001) and clinically (P = 0.015). The use of a dermatoscope increased accurate analysis of both groups for patients who required multiple stages. Dermatoscopy is a powerful tool, complementary to clinical examination and can be used to help delineate lesion borders prior to MMS, especially when evaluating complex skin lesions.

Treatment of Scleroderma-Related Microstomia Using Hyaluronic Acid: An Interventional Study.

Systemic sclerosis (SSc) or scleroderma is a rare, systemic, autoimmune connective tissue disease. It causes increased collagen synthesis, leading to multi-organ sclerosis, including the skin and joints. Patients' overall health and quality of life are harmed dramatically. Involvement of the face and, especially, the oral opening can limit patients' ability to speak and eat, oral hygiene, and cosmetic appearance. Profhilo® (NAHYCO®) is an over-the-counter product consisting of pure hyaluronic acid. It is used to improve skin quality by increasing collagen production and adipocyte vitality. This interventional study evaluated the results of perioral injections of hyaluronic acid in terms of improved skin quality, elasticity, and increased oral opening. Patients diagnosed with SSc received an injection of one syringe of Profhilo® (2 mL of hyaluronic acid) at each of two clinic visits at one-month intervals. The oral opening was measured between the upper and lower central incisors before and after treatment. Quality of life was assessed using the modified Rodnan Skin Score and Health Assessment Questionnaire-Disability Index. A total of 14 patients received the first treatment, and 11 received the second treatment. The mean oral opening increased from 31.6 mm (range 17-50 mm) prior to therapy to 35.8 mm (range 21-56) 2 months following the second injection. Statistical analysis showed that there was a significant increase in the oral opening as observed one week (36.2 mm, p = 0.011), one month (36.2 mm, p = 0.007), and three months (31.6 mm, p = 0.023) after the second injection, at the 5-month follow-up. Treatment of SSc patients' perioral area with Profhilo® can result in significant improvements in oral opening and quality of life.