Current Practice in Keloid Treatment: a Survey of Dutch Dermatologists and Plastic Surgeons.

BACKGROUND: Several therapeutic options are available for the treatment of keloids, but it remains unclear which treatment options are most commonly used by practitioners. OBJECTIVE: To explore the prevailing treatment for different keloid phenotypes among dermatologists and plastic surgeons in the Netherlands. METHODS: Members of the Dutch society for Plastic surgery and the Dutch society for Dermatology and Venereology were asked to participate. Questions elaborated on the treatment for a small and a large keloid on the mandibula and multiple keloids on the chest. RESULTS: One hundred forty-three responses were obtained. Heterogeneity in treatment was extremely high for the small, large, and multiple keloids with 27, 35, and 33 various first choices, respectively. Intralesional corticosteroids were most often chosen for all 3 different keloid phenotypes. These were mostly (61%) administered as monotherapy for the small keloid and mostly combined with other treatments for the large keloid (19%) and multiple keloids (43%). Surgery was chosen regularly (22%) for the large keloid, mostly combined with intralesional corticosteroids (10%) or brachytherapy (8.4%). CONCLUSION: Keloid treatment is very heterogeneous among dermatologists and plastic surgeons, even in a relatively small country as the Netherlands. Moreover, the treatment choice depends on the keloid phenotype.

The Development of the Cleft Aesthetic Rating Scale: A New Rating Scale for the Assessment of Nasolabial Appearance in Complete Unilateral Cleft Lip and Palate Patients.

OBJECTIVE: The development of the Cleft Aesthetic Rating Scale, a simple and reliable photographic reference scale for the assessment of nasolabial appearance in complete unilateral cleft lip and palate patients. DESIGN: A blind retrospective analysis of photographs of cleft lip and palate patients was performed with this new rating scale. SETTING: VU Medical Center Amsterdam and the Academic Center for Dentistry of Amsterdam. PATIENTS: Complete unilateral cleft lip and palate patients at the age of 6 years. MAIN OUTCOME MEASURES: Photographs that showed the highest interobserver agreement in earlier assessments were selected for the photographic reference scale. Rules were attached to the rating scale to provide a guideline for the assessment and improve interobserver reliability. Cropped photographs revealing only the nasolabial area were assessed by six observers using this new Cleft Aesthetic Rating Scale in two different sessions. RESULTS: Photographs of 62 children (6 years of age, 44 boys and 18 girls) were assessed. The interobserver reliability for the nose and lip together was 0.62, obtained with the intraclass correlation coefficient. To measure the internal consistency, a Cronbach alpha of .91 was calculated. The estimated reliability for three observers was .84, obtained with the Spearman Brown formula. CONCLUSION: A new, easy to use, and reliable scoring system with a photographic reference scale is presented in this study.

Detrimental dermal wound healing: what can we learn from the oral mucosa?

Wounds in adults are frequently accompanied by scar formation. This scar can become fibrotic due to an imbalance between extracellular matrix (ECM) synthesis and ECM degradation. Oral mucosal wounds, however, heal in an accelerated fashion, displaying minimal scar formation. The exact mechanisms of scarless oral healing are yet to be revealed. This review highlights possible mechanisms involved in the difference between scar-forming dermal vs. scarless oral mucosal wound healing. Differences were found in expression of ECM components, such as procollagen I and tenascin-C. Oral wounds contained fewer immune mediators, blood vessels, and profibrotic mediators but had more bone marrow-derived cells, a higher reepithelialization rate, and faster proliferation of fibroblasts compared with dermal wounds. These results form a basis for further research that should be focused on the relations among ECM, immune cells, growth factors, and fibroblast phenotypes, as understanding scarless oral mucosal healing may ultimately lead to novel therapeutic strategies to prevent fibrotic scars.

Baker Grade IV Capsular Contracture Is Correlated with an Increased Amount of Silicone Material: An Intrapatient Study.

BACKGROUND: Breast implant surgery is one of the most frequently performed procedures by plastic surgeons worldwide. However, the relationship between silicone leakage and the most common complication, capsular contracture, is far from understood. This study aimed to compare Baker grade I with Baker grade IV capsules regarding their silicone content in an intradonor setting, using two previously validated imaging techniques. METHODS: Twenty-two donor-matched capsules from 11 patients experiencing unilateral complaints were included after bilateral explantation surgery. All capsules were examined using both stimulated Raman scattering (SRS) imaging and staining with modified oil red O (MORO). Evaluation was done visually for qualitative and semiquantitative assessment and automated for quantitative analysis. RESULTS: Using both SRS and MORO techniques, silicone was found in more Baker grade IV capsules (eight of 11 and 11 of 11, respectively) than in Baker grade I capsules (three of 11 and five of 11, respectively). Baker grade IV capsules also showed significantly more silicone content compared with the Baker grade I capsules. This was true for semiquantitative assessment for both SRS and MORO techniques ( P = 0.019 and P = 0.006, respectively), whereas quantitative analysis proved to be significant for MORO alone ( P = 0.026 versus P = 0.248 for SRS, respectively). CONCLUSIONS: In this study, a significant correlation between capsule silicone content and capsular contracture is shown. An extensive and continued foreign body response to silicone particles is likely to be responsible. Considering the widespread use of silicone breast implants, these results affect many women worldwide and warrant a more focused research effort. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Patient-reported systemic symptoms in women with silicone breast implants: a descriptive cohort study.

OBJECTIVE: An unknown portion of women with silicone breast implants (SBI) report development of systemic symptoms, recently named as 'breast implant illness (BII)'. We aim to describe the symptoms and characteristics of women with SBI reporting these systemic symptoms and compare the clinical course of women who chose to keep their implants, to women who had their implants removed. DESIGN: Observational cohort study. SETTING: Specialised BII out-patient clinic at Amsterdam UMC, the Netherlands, from 2011 to 2020. PARTICIPANTS: All women presenting to the BII clinic with SBI and systemic symptoms. RESULTS: 467 women were included for baseline analyses and 398 women for follow-up. Most frequently reported systemic symptoms at baseline included fatigue (88%), arthralgia (71%), morning stiffness (59%), myalgia (48%), cognitive impairment (33%), peripheral neurological symptoms (30%) and lymphadenopathy (22%). Furthermore, 56% reported pre-existing allergies at baseline and positive antinuclear antibodies were observed in 23%. At follow-up with a median of 3.3 years (IQR 2-4), 152 women had their implants removed on clinical grounds. Symptoms improved significantly in 65 women (43%), improved moderately in 37 women (24%), did not change in 37 women (24%) and deteriorated in 13 women (9%). Women who underwent explantation showed more improvement of their systemic symptoms compared with women who did not (OR 2.9, 95% CI 1.3 to 6.2). Additionally, women who underwent explantation within 10 years after implantation improved significantly better than women who got the implants removed after 10 years (p=0.007). Lastly, local symptoms decreased from 75% to 34% after implant removal (p<0.0001). CONCLUSION: Most women with SBI who developed systemic symptoms experienced improvement after explantation, especially when removed within 10 years after implantation. Early recognition of the pattern of systemic symptoms in women with SBI is important and implant removal should be considered.

The Bigger Picture: Why Oral Mucosa Heals Better Than Skin.

Wound healing is an essential process to restore tissue integrity after trauma. Large skin wounds such as burns often heal with hypertrophic scarring and contractures, resulting in disfigurements and reduced joint mobility. Such adverse healing outcomes are less common in the oral mucosa, which generally heals faster compared to skin. Several studies have identified differences between oral and skin wound healing. Most of these studies however focus only on a single stage of wound healing or a single cell type. The aim of this review is to provide an extensive overview of wound healing in skin versus oral mucosa during all stages of wound healing and including all cell types and molecules involved in the process and also taking into account environmental specific factors such as exposure to saliva and the microbiome. Next to intrinsic properties of resident cells and differential expression of cytokines and growth factors, multiple external factors have been identified that contribute to oral wound healing. It can be concluded that faster wound closure, the presence of saliva, a more rapid immune response, and increased extracellular matrix remodeling all contribute to the superior wound healing and reduced scar formation in oral mucosa, compared to skin.

Therapeutic hotline: An alternative adjuvant treatment after ear keloid excision using a custom-made methyl methacrylate stent.

The efficacy of most pressure devices developed for treatment of ear keloids is limited by the insufficient control of the applied pressure, sometimes causing pain and repeated bleeding with a subsequently increased risk of infections and cosmetic problems. The present study aims to describe the efficacy of the custom-made methyl methacrylate stent in patients that were surgically treated for ear keloids and afterward underwent pressure therapy. The recurrence rate of the ear keloids was evaluated after at least 12 months. Adjuvant treatment with the methyl methacrylate stent resulted in an 83% success rate in our experience with 23 patients that completed the intended therapeutic duration of 18 months. No cases of severe complications were seen during or after the treatment. Furthermore, all the items of the Patient and Observer Scar Assessment Scale resulted in a statistically significant improvement of the scar (p < 0.05). Postoperative pressure therapy with the custom-made methyl methacrylate stent seems efficacious, safe, and is usable for keloids of both the helix and the earlobe.

Label-free stimulated Raman scattering imaging reveals silicone breast implant material in tissue.

Millions of women worldwide have silicone breast implants. It has been reported that implant failure occurs in approximately a tenth of patients within 10 years, and the consequences of dissemination of silicone debris are poorly understood. Currently, silicone detection in histopathological slides is based on morphological features as no specific immunohistochemical technique is available. Here, we show the feasibility and sensitivity of stimulated Raman scattering (SRS) imaging to specifically detect silicone material in stained histopathological slides, without additional sample treatment. Histology slides of four periprosthetic capsules from different implant types were obtained after explantation, as well as an enlarged axillary lymph node from a patient with a ruptured implant. SRS images coregistered with bright-field images revealed the distribution and quantity of silicone material in the tissue. Fast and high-resolution imaging of histology slides with molecular specificity using SRS provides an opportunity to investigate the role of silicone debris in the pathophysiology of implant-linked diseases.

No efficacy for silicone gel sheeting in prevention of abnormal scar formation in children with cancer: a randomized controlled trial.

BACKGROUND: Placement of a totally implantable venous access device in children with cancer often leads to hypertrophic scars after its removal. This study investigates whether the use of silicone gel sheets has a beneficial effect on scar outcome in children with cancer. METHODS: In a three-arm randomized controlled trial, the effects of use of silicone gel sheets for 2 and 6 months were assessed and compared with no intervention in children with cancer after removal of the totally implantable venous access device. Silicone gel sheets were first administered 14 days after surgery. The 1-year follow-up included measurements at seven time points. Next to scar size assessment, the modified Vancouver Scar Scale was used to assess scar outcome. RESULTS: Thirty-six children participated. For hypertrophy, no significant differences were found between the two intervention groups and the control group. However, at 1-year follow-up, the 2-month application group showed significantly smaller scars compared with the group receiving silicone gel sheet treatment for 6 months (p = 0.04), but not when compared with the control group (p = 0.22). Longitudinal multilevel analyses could not confirm these findings and showed no significant intervention effects on both outcomes. CONCLUSIONS: This study provides no strong evidence to support the use of silicone gel sheets after totally implantable venous access device removal in children with cancer. There seems to be a small benefit for scar width with application for 2 months. However, for hypertrophy, the scar outcome shows no significant difference between the control group and the 2-month and 6-month treatment groups.

Platelet derived growth factor-CC secreted by M2 macrophages induces alpha-smooth muscle actin expression by dermal and gingival fibroblasts.

Dermal wounds can heal detrimentally by formation of excess fibrosis or hypertrophic scarring. These phenomena are normally absent in the oral mucosa. Macrophages play an important role in wound repair, have a marked heterogeneity and are thought to contribute to fibrosis. To investigate to what extend macrophages are involved in the occurrence of fibrosis, the effect of differently activated macrophages on dermal and gingival fibroblasts was studied in vitro. Macrophages were differentiated into a classical (M1) or alternative (M2) phenotype, which was assessed by receptor expression (CD40/mannose receptor) and cytokine secretion (interleukin-4 and -12). Fibroblasts were exposed to these macrophages and/or conditioned medium (cm), and differentiation into α-SMA-expressing myofibroblasts was quantified. M2, but not M1 macrophages induced α-SMA expression in both dermal and gingival fibroblasts. Blocking of transforming growth factor-ß1 did not decrease the α-SMA expression mediated by M2 macrophages. It appeared that this induction was mediated by platelet derived growth factor-CC (PDGF-CC), produced by M2 macrophages. The expression and role of this growth factor was confirmed by ELISA, RT-PCR, and blocking experiments. Our results indicate that M2 macrophages are able to induce myofibroblast differentiation via production of PDGF-CC. Based on our findings we conclude that PDGF-CC may play a hitherto unknown role in the differentiation of myofibroblasts.

Prevention and curative management of hypertrophic scar formation.

Although hypertrophic scarring commonly occurs following burns, many aspects such as incidence of and optimal treatment for scar hypertrophy remain unclear. This review will focus on hypertrophic scar formation after burn in particular, exploring multiple treatment options and describing their properties as well as effectiveness. To evaluate treatment efficacy and scar development, clinical scar assessment is of eminent importance. Furthermore, recommendations regarding the classification of hypertrophy in the daily practice and in clinical trials are implemented.