[Analysis of the postoperative outcome of 81 cases of nasal reconstruction with direct closure]. / Analyse des postoperativen Verlaufs nach 81 Dehnungsplastiken an der Nase.

BACKGROUND: Direct wound closure (side-to-side closure) for closing nasal defects, is controversially discussed. Yet, data supporting one or the other are lacking. MATERIAL AND METHOD: An explorative, partly retrospective, partly prospective observational study including 81 patients was carried out for assessment of the operative results of after direct wound closure stretching rhinoplasty. The occurrence of complications, the esthetic result and influencing factors were examined. To assess the esthetic result the patient and observer scar assessment scale (POSAS) scores of patients and observers were determined. In both scores seven values were determined (1 point normal skin, 10 points worst imaginable scar). The individual values were added to give a total value (minimum 7-maximum 70). RESULTS: After direct wound closure stretching rhinoplasty, 12 out of 81 patients (15 %) developed complications, in 5 cases suture dehiscence, in 5 cases cyst formation, in 4 cases a wound infection and 2 patients developed cyst formation and a wound infection. All suture dehiscences occurred on the lower third of the nose. Most of the patients were satisfied and assessed the scar with an average total value of 13.4 ± 7.07 (minimum 7, maximum 70, n = 42). In the individual assessments pain (1.14 ± 0.57; minimum 1, maximum 10) was rated best and scar color (2.50 ± 1.76; minimum 1, maximum 10) was rated worst. The total assessment in the observer-POSAS was also good with 12.9 ± 4.8 (minimum 7, maximum 70; n = 32). Elasticity was rated best (1.47 ± 0.88; minimum 1, maximum 7) and scar pigmentation (2.34 ± 1.54; minimum 1, maximum 7) worst. No correlations with a complication were found. CONCLUSION: Direct wound closure stretching rhinoplasty is a safe method, especially for defect coverage in the upper two thirds of the soft tissue covering the nose, which in most cases achieved a good cosmetic result.

S3 guideline "actinic keratosis and cutaneous squamous cell carcinoma" - update 2023, part 2: epidemiology and etiology, diagnostics, surgical and systemic treatment of cutaneous squamous cell carcinoma (cSCC), surveillance and prevention.

Actinic keratosis (AK) are common lesions in light-skinned individuals that can potentially progress to cutaneous squamous cell carcinoma (cSCC). Both conditions may be associated with significant morbidity and constitute a major disease burden, especially among the elderly. To establish an evidence-based framework for clinical decision making, the guideline "actinic keratosis and cutaneous squamous cell carcinoma" was updated and expanded by the topics cutaneous squamous cell carcinoma in situ (Bowen's disease) and actinic cheilitis. The guideline is aimed at dermatologists, general practitioners, ear nose and throat specialists, surgeons, oncologists, radiologists and radiation oncologists in hospitals and office-based settings, as well as other medical specialties, policy makers and insurance funds involved in the diagnosis and treatment of patients with AK and cSCC. A separate guideline exists for patients and their relatives. In this part, we will address aspects relating to epidemiology and etiology, diagnostics, surgical and systemic treatment of cutaneous squamous cell carcinoma (cSCC), surveillance and prevention.

Primary tumor-derived systemic nANGPTL4 inhibits metastasis.

Primary tumors and distant site metastases form a bidirectionally communicating system. Yet, the molecular mechanisms of this crosstalk are poorly understood. Here, we identified the proteolytically cleaved fragments of angiopoietin-like 4 (ANGPTL4) as contextually active protumorigenic and antitumorigenic contributors in this communication ecosystem. Preclinical studies in multiple tumor models revealed that the C-terminal fragment (cANGPTL4) promoted tumor growth and metastasis. In contrast, the N-terminal fragment of ANGPTL4 (nANGPTL4) inhibited metastasis and enhanced overall survival in a postsurgical metastasis model by inhibiting WNT signaling and reducing vascularity at the metastatic site. Tracing ANGPTL4 and its fragments in tumor patients detected full-length ANGPTL4 primarily in tumor tissues, whereas nANGPTL4 predominated in systemic circulation and correlated inversely with disease progression. The study highlights the spatial context of the proteolytic cleavage-dependent pro- and antitumorigenic functions of ANGPTL4 and identifies and validates nANGPTL4 as a novel biomarker of tumor progression and antimetastatic therapeutic agent.

[Assessment of an e­learning platform for dermatosurgery]. / Beurteilung einer E­Learning-Plattform für Dermatochirurgie.

BACKGROUND: Dermatosurgical (DS) teaching is based on a combination of reading/understanding textbooks and applying surgical procedures (±â€¯supervision). Most textbooks are primarily text-centered. The text is visually supported by photos/sketches (S) and possibly videos (V). A learning goal of this teaching should be that the learner is confident to perform a procedure independently. METHODS: We have developed an online-based platform, the FlapFinder (FF; www.skin-surgery.org ), which teaches the user DS in the facial region primarily in the form of S + V. These are supported by a short text (T) and bonus material (B). B contains personal recommendations from the FF authors. A SurveyMonkey® (Survey Monkey, San Mateo, CA, USA) analysis should clarify how this is assessed by the user. RESULTS: In all, 62 participants completed the questionnaire in full. This was a heterogeneous group (27 dermatologists vs. 35 non-dermatologists; 32â€¯× clinic vs. 30â€¯× non-clinic) with different prior experience. The majority of users found that the combination of T + S + V helped them to understand (55/62; 88.7%), remember (53/62, 85.5%), and perform the procedures independently (43/62; 69.3%). While S + V were most frequently used (22/62; 35.5% and 27/62; 43.6%), users reported having benefited most from this (20/62; 32.3% and 24/62; 38.7%), T + B were used less (0/62, 0.0% and 2/62; 3.2%). Nevertheless, the majority would not want to do without either S, V, T, or B (49/62; 79%). CONCLUSION: The combination of S + V + T + B is rated positively by DS learners. S + V are rated as particularly helpful. Future studies must clarify whether the learning objective of the concrete practical performance of DS is changed by e­media.

Complete division of the pedicle of the forehead flap is possible after 1 week of engraftment in selected patients.

BACKGROUND: Recent studies have demonstrated that early division of the forehead flap (FHF) is possible if angiography is performed or a remnant of the pedicle is left behind. Whether or not careful selection of patients allows for complete division of the pedicle has not been studied. OBJECTIVE: To assess if careful selection of patients allows for early complete division of the FHF. METHODS: The exclusion criteria were trauma in the donor region, full-thickness defects, or a larger cartilage grafting. In the selected patients, complete division of the FHF pedicle was performed at early time points, when the pedicle was clinically engrafted (n = 12). RESULTS: The median age of the patients was 80 years ± 8. The average size of the wounds was 6.6 cm2 ± 4.0. The complete division of the pedicle was performed in 10 patients after 7 days, 1 patient after 8 days, and 1 patient after 11 days (median 7.4 days ± 1.1). One patient developed a wound infection, and 1 suffered from postoperative bleeding. The latter patient was the only 1 who required debulking in a third surgical procedure. No necrosis or flap failures were observed. LIMITATIONS: Retrospective, single-center study. CONCLUSION: Careful selection allows for complete early division of the pedicle of FHF.

Hygiene recommendations for outpatient dermatosurgery.

The German Infection Protection Act and country-specific laws demand appropriate measures to prevent nosocomial infections and propagation of pathogens, especially those with resistances. This also concerns outpatient surgery of the skin. Special focus is placed on hand hygiene, antiseptics, hygienic modes of operation and professional instrument reprocessing. Every dermatological institution that operates on an outpatient basis is obliged to organize and be responsible for its hygiene. The legal framework is regulated by various laws and regulations and must be observed.

Timed Ang2-Targeted Therapy Identifies the Angiopoietin-Tie Pathway as Key Regulator of Fatal Lymphogenous Metastasis.

Recent clinical and preclinical advances have highlighted the existence of a previously hypothesized lymphogenous route of metastasis. However, due to a lack of suitable preclinical modeling tools, its contribution to long-term disease outcome and relevance for therapy remain controversial. Here, we established a genetically engineered mouse model (GEMM) fragment-based tumor model uniquely sustaining a functional network of intratumoral lymphatics that facilitates seeding of fatal peripheral metastases. Multiregimen survival studies and correlative patient data identified primary tumor-derived Angiopoietin-2 (Ang2) as a potent therapeutic target to restrict lymphogenous tumor cell dissemination. Mechanistically, tumor-associated lymphatic endothelial cells (EC), in contrast to blood vascular EC, were found to be critically addicted to the Angiopoietin-Tie pathway. Genetic manipulation experiments in combination with single-cell mapping revealed agonistically acting Ang2-Tie2 signaling as key regulator of lymphatic maintenance. Correspondingly, acute presurgical Ang2 neutralization was sufficient to prolong survival by regressing established intratumoral lymphatics, hence identifying a therapeutic regimen that warrants further clinical evaluation. SIGNIFICANCE: Exploiting multiple mouse tumor models including a unique GEMM-derived allograft system in combination with preclinical therapy designs closely matching the human situation, this study provides fundamental insight into the biology of tumor-associated lymphatic EC and defines an innovative presurgical therapeutic window of migrastatic Ang2 neutralization to restrict lymphogenous metastasis.This article is highlighted in the In This Issue feature, p. 211.

[Personal preference, experience, intuition and school of surgery dominate the use of wound drainage in dermatosurgery]. / Persönliche Präferenz, Erfahrung, Intuition und operative Schule dominieren die Verwendung postoperativer Wunddrainagen in der Dermatochirurgie.

BACKGROUND: The use of drainage systems in dermatosurgery has so far been carried out without evidence-based data. The indications, complications and contraindications are traditionally passed on from surgeon to surgeon but have so far not been defined. METHOD: An Internet-based survey was created and sent out to members of the German Society for Dermatosurgery (DGDC). The questions were on the general treatment approach in German language countries with reference to the use of wound drainage following dermatological operations as well as the utilization habits and experiences with drainage-associated complications. RESULTS: Of the DGDC members contacted 12.73% completed the questionnaire. Drainages were predominantly used in the clinical environment and all drainage systems in question were used. The extent and complexity of the intervention were essential criteria when evaluating the indications. The use of drainages was dependent on the age of the participant and mostly carried out in patients where complications in the postoperative course were to be expected (e.g. obesity, nicotine use, diabetes). CONCLUSION: In summary, the majority of the participants used wound drainages and mostly intuitively. Uniform and fixed evidence-based parameters for the use of wound drainages are lacking. In the assessment of the necessity for a wound drainage, an individually expressed need of safety seems to play a large role for some dermatosurgeons and an eminence-based action for others.

Reconstruction of Full Thickness Defects on the Scalp With Artificial Dermal Regeneration Template: Analysis of Long-Term Results in 68 Cases.

BACKGROUND: Artificial skin substitute templates have been shown to be a reliable solution for the reconstruction of large scalp defects with exposed skull bone, but there is a lack of long-term data. OBJECTIVE: The aim of this retrospective study was to investigate the long-term outcome of the procedure in a large cohort of 68 cases. MATERIALS AND METHODS: In total, 58 patients with 68 full thickness scalp defects with exposed skull bone, were included. Mean follow-up time was 24 (±19) months. RESULTS: The mean size of the defects was 63 (±54) cm2. During the follow-up period, no local recurrences occurred. Complications were observed in 13% of the cases including template necrosis (4%), infections (4%), ulcerations (3%), and autograft necrosis (2%). During the final follow-up, 26 patients had died due to internal diseases not associated with the surgery. Cosmetic results were rated good by the patients and an independent observer. CONCLUSION: The use of a dermal regeneration template for the reconstruction of large, full thickness defects of the scalp with exposed skull bone is a reliable method regarding the complication rate, safety of the procedure, and cosmetic outcome. Limitations of this study are the retrospective and single center design.

Tumor Cell-Derived Angiopoietin-2 Promotes Metastasis in Melanoma.

The angiopoietin (Angpt)-TIE signaling pathway controls vascular maturation and maintains the quiescent phenotype of resting vasculature. The contextual agonistic and antagonistic Tie2 ligand ANGPT2 is believed to be exclusively produced by endothelial cells, disrupting constitutive ANGPT1-TIE2 signaling to destabilize the microvasculature during pathologic disorders like inflammation and cancer. However, scattered reports have also portrayed tumor cells as a source of ANGPT2. Employing ISH-based detection of ANGPT2, we found strong tumor cell expression of ANGPT2 in a subset of patients with melanoma. Comparative analysis of biopsies revealed a higher fraction of ANGPT2-expressing tumor cells in metastatic versus primary sites. Tumor cell-expressed Angpt2 was dispensable for primary tumor growth, yet in-depth analysis of primary tumors revealed enhanced intratumoral necrosis upon silencing of tumor cell Angpt2 expression in the absence of significant immune and vascular alterations. Global transcriptional profiling of Angpt2-deficient tumor cells identified perturbations in redox homeostasis and an increased response to cellular oxidative stress. Ultrastructural analyses illustrated a significant increase of dysfunctional mitochondria in Angpt2-silenced tumor cells, thereby resulting in enhanced reactive oxygen species (ROS) production and downstream MAPK stress signaling. Functionally, enhanced ROS in Angpt2-silenced tumor cells reduced colonization potential in vitro and in vivo. Taken together, these findings uncover the hitherto unappreciated role of tumor cell-expressed ANGPT2 as an autocrine-positive regulator of metastatic colonization and validate ANGPT2 as a therapeutic target for a well-defined subset of patients with melanoma. SIGNIFICANCE: This study reveals that tumor cells can be a source of ANGPT2 in the tumor microenvironment and that tumor cell-derived ANGPT2 augments metastatic colonization by protecting tumor cells from oxidative stress.