Dissemination of cancer cells from primary to distant sites is a complex process; little is known about the genesis of metastatic changes during disease development. Here we show that the metastatic potential of E2F1-dependent circulating tumour cells (CTCs) relies on a novel function of the hyaluronan-mediated motility receptor RHAMM. E2F1 directly up-regulates RHAMM, which in turn acts as a co-activator of E2F1 to stimulate expression of the extracellular matrix protein fibronectin. Enhanced fibronectin secretion links E2F1/RHAMM transcriptional activity to integrin-β1-FAK signalling associated with cytoskeletal remodelling and enhanced tumour cell motility. RHAMM depletion abolishes fibronectin expression and cell transmigration across the endothelial layer in E2F1-activated cells. In a xenograft model, knock-down of E2F1 or RHAMM in metastatic cells protects the liver parenchyma of mice against extravasation of CTCs, whereas the number of transmigrated cells increases in response to E2F1 induction. Expression data from clinical tissue samples reveals high E2F1 and RHAMM levels that closely correlate with malignant progression. These findings suggest a requirement for RHAMM in late-stage metastasis by a mechanism involving cooperative stimulation of fibronectin, with a resultant tumourigenic microenvironment important for enhanced extravasation and distant organ colonization. Therefore, stimulation of the E2F1-RHAMM axis in aggressive cancer cells is of high clinical significance. Targeting RHAMM may represent a promising approach to avoid E2F1-mediated metastatic dissemination.

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Aim: In this review, we outline similarities between conjunctival and skin melanoma as well as the effectiveness of combined BRAF/MEK inhibition in melanoma, and discuss the applicability of these agents in conjunctival melanoma. Methods: The study provides a PubMed literature review. Results: Conjunctival melanoma and skin melanoma are genetically and phenotypically related. Both tumors typically harbor BRAF mutations in more than 50% of cases. New targeted therapies in metastatic skin melanoma include selective inhibition of BRAF and MEK. Combined BRAF/MEK inhibition has revolutionized the treatment of metastatic skin melanoma, significantly improving patients' prognoses. While these new substances have been investigated extensively in the treatment of skin melanoma, comparable studies in conjunctival melanoma do not exist owing to the rarity of the malignancy. Conclusions: The application of combined BRAF/MEK inhibition in metastatic or unresectable conjunctival melanoma shows great potential for improving patients' prognoses. Future studies are needed to investigate the assumed benefit.

Background: The three-dimensional surface imaging system is becoming more common in plastic surgeries. However, few studies have assessed three-dimensional periocular structures and surgical outcomes. This study aimed to propose a standardized three-dimensional anthropometric protocol for the periocular region, investigate its precision and accuracy, and determine the three-dimensional periocular anthropometric norms for young Caucasians. Methods: Thirty-nine healthy young Caucasians (78 eyes) were enrolled. Three-dimensional facial images were obtained with a VECTRA M3 stereophotogrammetry device. Thirty-eight measurements in periocular regions were obtained from these images. Every subject underwent facial surface capture twice to evaluate its precision. A paper ruler was applied to assess its accuracy. Results: Sixty-three percent of measurements in linear distances, curvatures, angles, and indices were found to reach a statistically significant difference between sexes (p ≤ 0.05, respectively). Across all measurements, the average mean absolute difference was 0.29 mm in linear dimensions, 0.56 mm in curvatures, 1.67 degrees in angles, and 0.02 in indices. In relative error of magnitude, 18 percent of the measurements were determined excellent, 51 percent very good, 31 percent good, and none moderate. The mean value of the paper-ruler scale was 10.01 ± 0.05 mm, the mean absolute difference value 0.02 mm, and the relative error of magnitude 0.17 percent. Conclusions: This is the first study to propose a detailed and standardized three-dimensional anthropometric protocol for the periocular region and confirm its high precision and accuracy. The results provided novel metric data concerning young Caucasian periocular anthropometry and determined the variability between sexes.

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ZusammenfassungMit dem Einsatz von Mikroendoskopen in der Tränenwegchirurgie und dem dadurch bedingten Einzug der neueren, transkanalikulären, anatomieerhaltenden Operationsverfahren wurden verschiedenste Tränenwegintubationssysteme entwickelt. Je nach Lokalisation und Ausmaß der Tränenwegstenose können bikanalikuloanuläre, monokanalikuläre, monokanalikulonasale, bikanalikuläre und bikanalikulonasale Intubationstechniken und -systeme sowie Kombinationen daraus zum Einsatz kommen. Der isolierten Intubation der Tränenpünktchen dienen perforierte Punctum Plugs, während eine rein monokanalikuläre Intubation mit einer Mini-Monoka® erfolgen kann. Als monokanalikulonasale Intubationssysteme stehen neben der Monoka (Wide-Collarette-Typ), der Monoka von Fayet (Crawford-Typ), der selbsteinfädelnde Monoka (Ritleng®-Typ), der Masterka® sowie der LacriJet® für den ophthalmoplastischen Chirurgen zur Auswahl. Zu den bikanalikulonasalen Intubationssystemen zählen verschiedene BIKA®-Systeme, das Ritleng-Intubationssystem, das Crawford-Intubationsset und der FCI Nunchaku®. Indikationen sowohl für monokanalikulonasale als auch bikanalikulonasale Intubationssysteme stellen kanalikuläre Obstruktionen, Stenosen oder Lazerationen aller Art sowie sakkale und postsakkale Obstruktionen und Stenosen nach deren Eröffnung oder nach einer Dakryozystorhinostomie (DCR) dar. Bei einer Konjunktivodakryozystorhinostomie (CDCR) können bspw. die klassischen Lester Jones Tubes, Metaireau Tubes oder die StopLoss® Jones Tubes verwendet werden. Obwohl die Studienlage nicht eindeutig ist und daher eine Tränenwegintubation nicht als obligat angesehen werden darf, verzichten die meisten Ophthalmochirurgen trotz höherer Kosten und einer geringfügig längeren Operationsdauer in den meisten Fällen nicht auf eine solche. Für welches Intubationssystem der Operateur sich letztendlich entscheidet, hängt in den meisten Fällen von der gewählten Intubationsform, den Kosten sowie seinen persönlichen Präferenzen und Erfahrungen ab.

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