Tspan8 is expressed in breast cancer and regulates E-cadherin/catenin signalling and metastasis accompanied by increased circulating extracellular vesicles

Tspan8 exhibits a functional role in many cancer types including pancreatic, colorectal, oesophagus carcinoma, and melanoma. We present a first study on the expression and function of Tspan8 in breast cancer. Tspan8 protein was present in the majority of human primary breast cancer lesions and metastases in the brain, bone, lung, and liver. In a syngeneic rat breast cancer model, Tspan8⁺ tumours formed multiple liver and spleen metastases, while Tspan8⁻ tumours exhibited a significantly diminished ability to metastasise, indicating a role of Tspan8 in metastases. Addressing the underlying molecular mechanisms, we discovered that Tspan8 can mediate up-regulation of E-cadherin and down-regulation of Twist, p120-catenin, and β-catenin target genes accompanied by the change of cell phenotype, resembling the mesenchymal–epithelial transition. Furthermore, Tspan8⁺ cells exhibited enhanced cell–cell adhesion, diminished motility, and decreased sensitivity to irradiation. As a regulator of the content and function of extracellular vesicles (EVs), Tspan8 mediated a several-fold increase in EV number in cell culture and the circulation of tumour-bearing animals. We observed increased protein levels of E-cadherin and p120-catenin in these EVs; furthermore, Tspan8 and p120-catenin were co-immunoprecipitated, indicating that they may interact with each other. Altogether, our findings show the presence of Tspan8 in breast cancer primary lesion and metastases and indicate its role as a regulator of cell behaviour and EV release in breast cancer. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

Use of stereolithographic drilling and cutting guides in bilateral mandibular distraction

Mandibular distraction osteogenesis is used in the treatment of patients with syndromic and nonsyndromic class II mandibular hypoplasia. The three-dimensional distraction of the mandible is extremely complex. Past experience with mandibular distraction has demonstrated the indispensability of solid presurgical planning to achieve predictable results. We report a method for a virtual three-dimensional planning of the bilateral mandibular distraction with intraoperative transfer by stereolithographic guides. Five patients (mean age, 22.8 years) with bilateral mandibular hypoplasia were examined with preoperative and postoperative computed tomographic scans. The direction and dimension of the distraction were planned on the three-dimensional computed tomographic scans. Tooth- and bone-borne stereolithographic guides for transferring the planning were then applied intraoperatively. It was feasible to transfer and perform the surgery as planned by the use of the stereolithographic drilling and cutting guides. The mean distraction width was 11.33 (SD, 8.32) mm. The mean difference of the distraction width between the planning and the achieved final mandibular position was 1.80 (SD, 0.43) mm. The intercondyle distance decreased by 3.28 (SD, 1.01) mm. A parallel distraction within the planned vectors was achieved. Mandibular distraction osteogenesis in the treatment of severe mandibular hypoplasia needs careful presurgical planning. Parallel distraction and fast placement of the distractors are provided by the planning. The method provides a useful tool for both planning and intraoperative transfer of the virtually preplanned distraction vectors.     

3-Tesla-MRT von seltenen zystisch imponierenden Prostatakarzinomen

Magnetic resonance imaging of rare cystic prostate cancers using multiparametric MRI (mp-MRI, 3 Tesla) shows, especially in solid tumor masses, the criteria of ESUR-MR classification with a PI-RADS >3 (“probably malignant”). In association with additional morphological evidence of intracystic hemorrhage and evidence of villous tumor nodules and irregular septa on the cyst wall, further malignancy criteria are met. MRI complementary to TRUS may be useful for targeted biopsy in solid tumor areas.     

The effect of the intrathoracic pressure regulator on hemodynamics and cardiac output

The intrathoracic pressure regulator (ITPR) (CirQLator; Advanced Circulatory Systems Inc, Roseville, Minn) is a novel, noninvasive device intended to increase cardiac output and blood pressure in hypovolemic or cardiogenic shock by generating a continuous low-level intrathoracic vacuum in between positive pressure ventilations. Although there are robust data supporting the benefit of the ITPR in multiple animal models of shock, the device has not been used in humans.The goals of this study were to evaluate both the safety and efficacy of the ITPR in humans. Twenty patients undergoing coronary artery bypass graft surgery were enrolled in this phase 1 study. Intraoperative use of both pulmonary artery pressure monitoring and transesophageal echocardiography (TEE) was required for study inclusion. Hemodynamic variables as well as TEE measurements of left ventricular performance were collected at baseline and after the ITPR device was activated, before surgical incision. Thermodilution cardiac output increased significantly with the application of the ITPR (4.9 vs. 5.5 L/min; P = 0.017). Similarly, cardiac output was measured by TEE (5.1 vs. 5.7 L/min; P = 0.001).There were significant increases in pulmonary artery systolic blood pressures (35 vs. 38 mmHg; P G 0.001) and mean pulmonary artery pressures (24 vs. 26 mmHg; P = 0.008). There were no significant differences in systemic blood pressures, left ventricular volumes, stroke volume, or ejection fraction as measured by TEE. Using two different measurement techniques, application of the ITPR increased cardiac output in normovolemic anesthetized patients who underwent coronary artery bypass graft before sternotomy. These data suggest that the ITPR has the potential to safely and effectively increase cardiac output in humans.