[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.

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.

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.