Development of a cellular assay as a personalized model for testing chronic wound therapeutics.

Exudates of non-healing wounds contain drivers of pathogenicity. We utilized >800 exudates from non-healing and healing wounds of diverse etiologies, collected by three different methods, to develop a wound-specific, cell-based functional biomarker assay. Human dermal fibroblast proliferation served as readout to a) to differentiate between healing and non-healing wounds, b) follow the healing process of individual patients, and c) assess the effects of therapeutics for chronic wounds ex vivo. We observed a strong correlation between wound chronicity and inhibitory effects of individual exudates on fibroblast proliferation, with good diagnostic sensitivity (76-90%, depending on the sample collection method). Transition of a clinically non-healing to a healing phenotype restored fibroblast proliferation and extracellular matrix formation while reducing inflammatory cytokine production. Transcriptional analysis of fibroblasts exposed to ex vivo non-healing wound exudates revealed an induction of inflammatory cytokine- and chemokine pathways and the unfolded protein response, indicating that these changes may contribute to the pathology of non-healing wounds. Testing the wound therapeutics platelet derived growth factor and silver sulfadiazine yielded responses in line with clinical experience and indicate the usefulness of the assay to search for and profile new therapeutics.

Surgical Therapy of Congenital Nevi in the First Year of Life-Psychological Impact on Parents.

BACKGROUND: The birth of a child with a congenital melanocytic nevus (CMN) can lead to distress in the parents. Surgical treatment of CMN can begin in infancy. OBJECTIVES: To provide insight into the perspective of parents of children with CMN regarding their experienced psychological burden and motivation to undergo surgery as well as their satisfaction. METHODS: Retrospective analysis of patient data of infants (< 1 year of age), who were surgically treated by power stretching for CMN using subcutaneous infiltration anesthesia (SIA) from 01/01/2020 to 08/31/2021. To evaluate the parent's motivation and psychological burden during the surgical treatment of their child, a questionnaire was designed to interview them in a standardized telephone-based interview. RESULTS: Out of 45 interviewed parents, 62.2% indicated "severe" or "very severe" distress at the time of their child's birth. Distress was mostly reduced by information about diagnosis and treatment (n = 34) and treatment-progress (n = 27). Stigmatization was experienced by 35.6% of parents. 84,5% of parents were highly satisfied with early initiation of surgical therapy. 69% felt "very satisfied" or "satisfied" with the outcome of surgery. Motivation for surgical therapy was concern about malignant transformation of the, possible stigmatization of the child due to the nevus, while most of the parents (73.3%) mentioned both. CONCLUSIONS: Surgical treatment of CMN by power stretching in SIA in infancy is associated with high levels of satisfaction among the children's parents. Early initiation of surgical therapy and education about the diagnosis can reduce the psychological burden of the parents and can prevent psychosocial problems in affected children.

[Micrographic controlled surgery in everyday dermatosurgery]. / Mikroskopisch kontrollierte Chirurgie im dermatochirurgischen Alltag.

Micrographic controlled surgery (MCS) has become established in dermatosurgery in recent years and includes various methods to enable the histologically proven complete resection of malignant cutaneous tumors, while at the same time sparing tumor-free tissue in the immediate vicinity as much as possible. MCS is of great importance in the surgical treatment of cutaneous malignancies in so-called problem locations and aggressive tumor subtypes. Indications for MCS include basal cell carcinoma, cutaneous squamous cell carcinoma, Bowen's disease and Bowen's carcinoma, melanoma in chronic light-damaged skin with acral lentiginous melanoma, dermatofibrosarcoma protuberans (DFSP), and Merkel cell carcinoma. However, other tumor entities are also treated using MCS, such as extramammary Paget's disease and various cutaneous sarcomas. All procedures subsumed under MCS have in common the marking of the surgical specimen for topographical orientation, which provides assignment of remaining tumor remnants. Various methods of MCS (3D histology, the horizontal method or Mohs surgery) are presented in this article. Furthermore, this article aims to raise awareness of the possibilities and limitations of micrographically controlled surgery.

Influence of perioperative antiplatelet and anticoagulant medication management on bleeding events in dermatosurgery-A prospective observational study.

BACKGROUND: Perioperative management of antiplatelet and anticoagulant (AP/AC) therapy is a matter of balancing the risks of bleeding and thromboembolic events. Reliable data for dermatosurgery are still lacking, especially for direct oral anticoagulants (DOAC). OBJECTIVES: The aim was to prospectively evaluate the influence of AP/AC-medication on bleeding risk in dermatosurgery with focus on exact intervals between DOAC intake and procedure performed on post-operative bleeding. METHODS: Patients with or without AP/AC-therapy were included in the study without randomization. Exact times of DOAC-intake, procedure performed and post-operative bleeding were documented. Data collection was prospectively and standardized done by one person. RESULTS: We evaluated 1852 procedures in 675 patients. Post-operative bleeding occurred after 15.93% (n = 295) of all procedures, but only a few of them were severe (1.57%, n = 29). Compared to patients without AP/AC-medication, severe post-operative bleeding occurred significantly more often under dual antiplatelet therapy (11.76%, n = 2; p = 0.0166) and bridging of either vitamin K antagonist (9.09%, n = 2; p = 0.0270) or DOAC (15.38%, n = 2; p = 0.0099). There was no significant difference in the frequency of severe bleeding regarding to the preoperative DOAC-free period. CONCLUSIONS: Although AP/AC-therapy is associated with a significant higher rate of post-operative bleeding, no life-threatening bleeding was recorded. Long preoperative pausing or bridging of DOAC does not lead to significantly less severe bleeding events.

[Surgical treatment of nevi in children in a dermatological surgery center : Histopathology and complications]. / Operative Therapie von Nävi bei Kindern in einem dermatochirurgischen Zentrum : Histopathologie und Komplikationen.

BACKGROUND: The indication for surgical management and histological diagnosis of melanocytic nevi in children is a major challenge in clinical routine. In consultations with children and parents, the exclusion of malignant findings, on the one hand, and the risk of complications, on the other hand, are important. PATIENTS AND METHODOLOGY: Included were 946 children under the age of 10 years who underwent surgery with a suspected diagnosis of melanocytic nevus at the University Department of Dermatology, Tübingen, Germany, between 2008 and 2018. Dermatohistopathologic findings and postoperative complications were recorded. RESULTS: A clinical diagnosis of melanocytic nevus was histologically confirmed in 93.2% (882/946) of cases, whereby there were 41 Spitz nevi and 18 pigmented spindle cell tumors. Melanoma was diagnosed in 2 of the children (0.2%). In another 6.6%, non-melanocytic findings (e.g., nevus sebaceous, epidermal nevi) were diagnosed. The complication rate was low at 3%. The most common complication was the occurrence of postoperative wound infection in 1.7%. CONCLUSION: It is possible to take a biopsy or surgically remove congenital nevi of different sizes even in infants. Serial excision of congenital nevi is an important tool for this purpose. In the investigated cohort, the complication rate was low. Histological confirmation is essential in case of clinically suspicious or atypical findings.

Tumescent local anaesthesia for the surgical therapy of congenital nevi in the first year of life.

BACKGROUND: The indication for surgical treatment of congenital nevi must be made after individual consideration of the expected benefit and risk and requires careful information of the parents as well as interdisciplinary psychological support. In addition to suspected malignancy, a relevant indication is the risk of stigmatization depending on the size and localization of the nevus. Objective was to show which size reduction of the congenital nevus can be achieved by surgical therapy under tumescent local anaesthesia (TLA) in infancy and how often complications of anaesthesia or surgery occur. METHODS: All infants up to 12 months of age who underwent surgery for a congenital nevus under TLA at the University Dermatological Clinic Tuebingen between January 2015 and December 2021 were included; surgeries were performed using serial excisions (powerstretching technique), whereby the incisions were made inside the nevus and mobilization was strictly limited to the skin side without nevus. RESULTS: Overall, a cumulative total area of 38.65 cm2 could be removed on average within the first year of life (trunk: 67 cm2 , head: 21.2 cm2 , legs: 21.6 cm2 , arms: 13.2 cm2 ). A cumulative maximum area reduction of 406.9 cm2 could be achieved. We evaluated 363 surgical sites (123 children) on all body regions. The median age of the children at the first surgery was 3.5 months (0.46-10.7 months). Complications occurred in 2.3% (seven procedures). All these complications were reversible in the course of the operation and did not lead to a prolonged hospital stay. No anaesthesia-related complications occurred. CONCLUSION: We were able to show that a reduction of large areas of congenital nevi is possible in the first year of life with the combination of serial excisions using powerstretching technique, TLA, and intracutaneous butterfly sutures.

Concomitant thrombosis in patients with cellulitis as incidental finding.

BACKGROUND: Although inflammation and thrombosis are tightly connected, only 45% of patients with lower leg cellulitis receive anticoagulant therapy. Available data about the prevalence of concomitant deep venous thrombosis (DVT) in patients with cellulitis of the lower extremity is scarce and general guidelines regarding diagnosis and prevention of venous thromboembolism are missing. OBJECTIVE: We sought to determine how frequently DVT occurs as an incidental finding in patients with cellulitis and to provide recommendations for diagnostics and anticoagulant therapy. METHODS: Patients' records were analysed and 192 consecutive patients with cellulitis were included in this study. The prevalence of concomitant DVT was examined by duplex ultrasound, as well as comorbidities and risk factors. RESULTS: We detected thrombosis in 12.0% of the patients with lower leg cellulitis, of which 43.5% were located in a proximal vein and 52.2% in the veins of the calf. CONCLUSIONS: Our results clearly indicate that cellulitis is not only a differential diagnosis, but should be considered a risk factor for venous thrombosis. Therefore, prophylactic anticoagulation should be considered in patients suffering from cellulitis and a systematic screening for venous thrombosis in patients with cellulitis should be performed.

Modification of Skin Flaps for Single-Stage Reconstruction of the Nasal Ala Using All-Layer Suture: A Prospective Study.

BACKGROUND AND OBJECTIVES: After local flaps, it may be necessary to reconstruct the contour of the nasal ala. This is possible with a single-stage all-layer shaping suture. In the present study, the functional and aesthetic results after single-stage reconstruction of the nasal ala were prospectively evaluated. PATIENTS AND METHODS: Patients who underwent surgery for skin tumors of the nose between 06/2019 and 06/2020 who required reconstruction of the nasal ala as part of the defect closure and had an all-layer suture used were prospectively included in the study. A standardized evaluation of aesthetic and functional outcome was conducted by the patient and a physician at discharge as well as 4 weeks later. Patients additionally underwent a follow-up survey 6 months later. RESULTS: Thirty-seven patients were included in the study. Four weeks postoperatively, all flaps were found to be fully healed and vital. Aesthetic outcome at 4 weeks was rated as very good or good by physicians in 73% and by patients in 78.4%. Persistent complications due to reduced blood flow were not observed. CONCLUSION: The reshaping of the nasal ala as part of the defect reconstruction with an all-layer suture demonstrates very good aesthetic as well as functional results and can be performed in a single-stage procedure. .

Local Tumor Infiltration and Locoregional Recurrence in Desmoplastic Cutaneous Squamous Cell Carcinoma.

BACKGROUND: Perusal of the literature of cutaneous squamous cell carcinoma (SCC) reveals that the role of the desmoplastic subtype is indistinct. Data on local infiltration and recurrence are inconsistent dependent on surgical technique, histological method, and investigated collective. OBJECTIVE: The aim of the study was to analyze local infiltration and locoregional recurrence of the desmoplastic subtype under a uniform procedure. METHODS AND MATERIALS: Between 2005 and 2015, 320 SCCs were analyzed and histological sections of all tumors were examined. Data collection included locoregional recurrence, metastasis rate, and tumor-specific death. The median follow-up was 36.5 months. RESULTS: The desmoplastic subtype required significant more re-excisions (70.0% vs 23.9%, p < .001), more interventions until tumor-free margins were achieved (maximal 6 vs 2; p < .001), showed more widespread tumor infiltration with larger excisional margins (median 9 mm, 2-51 mm vs median 4 mm, 1-10 mm; p < .001), and a 5-fold higher local recurrence rate (26.7% vs 5.0%, p < .001). The metastasis rate (16.6% vs 2.3%, p < .001) was increased. CONCLUSION: The desmoplastic subtype is characterized by a widespread local infiltration associated with perineural infiltration. It seems to be a marker for decreased histological detectability with a high rate of locoregional recurrence and metastasis.

[Postoperative wound care with custom-made wound dressings for hidradenitis suppurativa : Wound care after radical excision with secondary wound closure]. / Postoperative Wundversorgung mit individuell angefertigten Wundauflagen bei Hidradenitis suppurativa : Wundversorgung nach radikaler Exzision mit sekundärem Wundverschluss.

Hidradenitis suppurativa is a chronic, recurrent, autoinflammatory skin disease of the hair follicle and sebaceous glands in intertriginous skin areas. Treatment is based on clinical severity (typically classified according to Hurley stage). In advanced stages, radical excision of affected skin areas with secondary wound closure remains first-line treatment. Postoperative care in this setting should comprise nonadhesive wound dressings. The purpose of this article is to illustrate postoperative wound care after radical excision with secondary wound closure using nonadhesive, absorbent dressings for economical and effective care.

The impact of haematoxylin-eosin staining and immunohistochemistry of lentigo maligna and lentigo maligna melanoma margins on local recurrence

Background: Local recurrence of lentigo maligna melanoma (LMM) and lentigo maligna (LM) continue to be challenging following surgical treatment and aftercare. Objectives: To investigate haematoxylin-eosin staining and immunohistochemistry of the tumour margins of LM and LMM and evaluate the impact of these data on local recurrence. Materials & Methods: In total, 489 tumours were included in this retrospective single-centre study, among them 199 (40.7%) LMs and 290 (59.3%) LMMs. All tumours were excised using micrographiccontrolled surgery. Additional immunohistochemistry staining of the tumour margins was performed in 35 specimens (7.2%). Results: Based on haematoxylin-eosin staining alone, 82/454 tumours (18.1%) were shown to develop local recurrence compared to 3/35 tumours (8.6%) when additional immunohistochemistry was performed. Conclusion: Following micrographic-controlled surgery, the additional use of immunohistochemistry of tumour margins of LM/LMM reduced the risk of local recurrence, although this was not statistically significant.

Intravenous Immunoglobulin Therapy in Livedoid Vasculopathy: Retrospective Observation of Clinical Outcome and Patient's Activity Level.

BACKGROUND: Livedoid vasculopathy (LV) is a rare disease characterized by livedo racemosa, atrophie blanche, ulcerations, and severe pain. Low molecular weight heparins and rivaroxaban can be used in LV-patients. In addition, intravenous immunoglobulins (IVIG) have been described as treatment-option. OBJECTIVES: Objective was to investigate the therapeutic effect of IVIG on ulcer, pain and restrictions in daily life. METHODS: Thirty-two LV-patients who received IVIG at the Department of Dermatology Tübingen between 01/2014 and 06/2019 were identified. Twenty-five of these patients were available for further follow up and were included in the study. Patients were interviewed using a questionnaire focusing on the course of the disease, symptoms, and subjective response to IVIG-treatment. RESULTS: Twenty-five patients were included in the study (mean follow up: 28.9 months). Patients received an average of 6.8 cycles (range 1-45) of IVIG during the observed period.Significant improvements were seen regarding skin findings, pain, and limitation of daily activities. Complete remission of symptoms was observed in 68% of patients. Good tolerability of IVIG was shown in 92%. CONCLUSIONS: A good therapy response regarding ulceration, pain, and daily life restrictions with good tolerability was demonstrated for IVIG (2 g/kg bodyweight over 5 days).

Post-operative follow-up of 150 patients with sentinel lymph node biopsy under tumescence local anesthesia.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is useful for staging of patients with melanoma. Although SLNB is mostly performed under general anesthesia (GA), tumescence local anesthesia (TLA) can also be used. However, less data are available regarding feasibility of SLNB under TLA. Here we present a post-operative follow-up of 150 patients. PATIENTS AND METHODS: We prospectively analyzed data from 150 patients with primary cutaneous malignant melanoma. We assessed pain, post-operative complications and patients' satisfaction after SLNB under TLA. RESULTS: 32 % of the patients reported post-operative pain within the first 48 h after SLNB. Seroma was the most frequent complication, as 29 seromas after SLNB were observed. Wound infection was observed in 3.3 % of the patients. 98.7 % of the patients were satisfied with SLNB under TLA. CONCLUSIONS: SLNB under TLA is a safe and feasible option and should be considered for patients with melanoma. Especially with multimorbid or elderly patients, the risks of GA can be avoided.

Local Recurrence Rates of Skin Tumors After Resection With Complete Circumferential Peripheral and Deep Margin Assessment-Identification of High-Risk Entities.

BACKGROUND: The local recurrence rates of malignant skin tumors after micrographic controlled surgery using complete circumferential peripheral and deep margin assessment (CCPDMA) are reported to be low. However, in daily practice, tumor entities with a significantly higher recurrence rate are found. OBJECTIVE: The aim of the investigation was to identify these high-risk tumors to develop approaches for risk stratification. PATIENTS AND METHODS: We included different malignant tumors that were surgically treated and examined with CCPDMA using paraffin sections and H&E staining. Re-excisions were performed until the tumor was completely removed. RESULTS: Ninety-nine thousand three hundred seventy-two tumors were included in the study; the follow-up period was 4 years (median). Eight tumor entities were identified as high-risk entities, showing a significantly higher local recurrence rate of over 20%: desmoplastic squamous cell carcinoma, desmoplastic melanoma, Merkel cell carcinoma, microcystic adnexal carcinoma, pleomorphic sarcoma, liposarcoma as well as angiosarcoma, and extramammary Paget's disease. CONCLUSION: Complete circumferential peripheral and deep margin assessment allows complete control of the resection margins and enables skin-sparing resections with low recurrence rates for basal cell carcinomas, nondesmoplastic squamous cell carcinomas, lentiginous melanomas, and dermatofibrosarcoma protuberans. However, other tumors show significantly higher recurrence rates and therefore need to be classified as high-risk tumors.