Validation of the European visual field standards for driving: A driving simulator-based study.

PURPOSE: To determine whether we could establish evidence-based pass/fail criteria for perimetry in the context of the European visual field standards for driving. METHODS: This two-centre, cross-sectional study included participants with binocular visual field loss that had led to revocation of a group-1 driving licence. The participants underwent cognitive and binocular visual testing, including the European Driving Test (EDT), a perimetry algorithm that adheres to the European visual field standards. We used a high-fidelity driving simulator to compare the driving ability of these participants with healthy controls. Two driving instructors classified each driving test as passed or failed. Receiver operating characteristic (ROC) analysis and area under the curve (AUC) determined the ability of perimetry to discriminate between passed and failed driving tests. RESULTS: The study included 70 participants with visual field loss and 37 controls. A non-significantly higher proportion of controls passed the driving test (75% vs. 63%; p = 0.22). In ROC analysis, contrast sensitivity performed best (AUC of 0.73), followed by NEI VFQ-25 (AUC of 0.64). Peripheral visual field (AUC of 0.56) and central visual field (AUC of 0.47) performed weaker. Combining the central and peripheral visual field, and their interaction, increased AUC to 0.63. CONCLUSION: Perimetry was a poor predictor of simulator-based driving test result, and we could not establish appropriate pass/fail criteria for the European visual field standards. Because perimetry is not an accurate diagnostic tool for fitness to drive, a practical driving assessment should be performed in case of doubt.

Sorafenib inhibits tumor growth and improves survival in a transgenic mouse model of pancreatic islet cell tumors.

BACKGROUND: The purpose of the study was to evaluate Sorafenib (BAY 43-9006) derived receptor tyrosine kinase inhibition on tumor progression in murine islet cell tumors. Sorafenib is considered to be a potent inhibitor of tumor angiogenesis and neovascularization in various solid tumors. Rip1Tag2 mice were treated in two different groups according to the model of tumor progression: the early treatment group received vehicle or Sorafenib from 10 to 14 weeks of age and the late treatment group from week 12 until death. Tumor surface, tumor cell proliferation, and apoptosis were measured in both treatment groups to assess the in vivo effects of Sorafenib. Survival was recorded for the late treatment group. In the early treatment group Sorafenib led to a dramatic decrease in tumor volume compared to the control group. Apoptosis was significantly augmented and cell proliferation was inhibited. As a single therapy Sorafenib significantly improved survival in the late treatment group. Conclusion. Sorafenib may provide a new paradigm for the therapy of islet cell tumors.

Hedgehog inhibition with the orally bioavailable Smo antagonist LDE225 represses tumor growth and prolongs survival in a transgenic mouse model of islet cell neoplasms.

BACKGROUND: This study was designed to evaluate the role of the hedgehog pathway in tumor progression of murine islet cell tumors. Blockade of aberrant hedgehog activation has recently been proposed as a therapeutic target, but effects in models of islet cell tumors with a new orally bioavailable Smoothened (Smo) antagonist LDE225 have not been examined. MATERIAL AND METHODS: To assess in vivo effects, transgenic Rip1Tag2 mice, which develop islet cell neoplasms, were treated with vehicle or LDE225 (80 mg/kg/d) from week 5 until death. The resected pancreata were evaluated macroscopically and microscopically by iummohistochemsistry. Quantitative real-time polymerase chain reaction was performed for hedgehog target genes with RNA from islet, isolated from treated and untreated Rip1Tag2 mice. RESULTS: LDE225 significantly reduced tumor volume by 95% compared with untreated control mice. Hedgehog inhibition with LDE225 significantly prolonged median survival in the used transgenic mouse model (105 vs 116 days; P = 0.02). Quantitative real-time polymerase chain reaction for downstream hedgehog target genes demonstrated significant downregulation in the islet cell tumors of Rip1Tag2 mice treated with LDE225, confirming the ability to achieve effective pharmacologic levels of LDE225 within the desired tissue site, in vivo. CONCLUSION: This is the first study to show that the orally bioavailable Smo antagonist LDE225 may provide a new option for therapy of islet cell neoplasms.

Hedgehog inhibition with cyclopamine represses tumor growth and prolongs survival in a transgenic mouse model of islet cell tumors.

BACKGROUND: Blockade of aberrant hedgehog (Hh) activation has recently been proposed as a therapeutic target, but effects in models of islet cell tumors have not been examined. In this study, we address the role of the Hh pathway in tumor progression of murine islet cell tumors. METHODS: To assess in vivo effects, Rip1Tag2 mice were treated with vehicle or cyclopamine (25 mg/kg/d) (n = 10 in each group). The effect of hedgehog pathway inhibition on survival was determined by continuous application of the small molecule smoothened antagonist cyclopamine. RESULTS: Hh-inhibition was confirmed by downregulation of Hh-target genes. Cyclopamine response was associated with increased apoptosis, decreased tumor cell proliferation and reduced tumor volume. Furthermore, hedgehog inhibition with cyclopamine significantly prolonged median survival in the used transgenic mouse model (102 vs 124 days; P = 0.02). CONCLUSIONS: Thus, Hh inhibitors may provide a new paradigm for therapy of islet cell tumors in various stages, particularly their use in conjunction with conventional antimetabolites should be further evaluated.

3D-modeling of the spine using EOS imaging system: Inter-reader reproducibility and reliability.

OBJECTIVES: To retrospectively assess the interreader reproducibility and reliability of EOS 3D full spine reconstructions in patients with adolescent idiopathic scoliosis (AIS). METHODS: 73 patients with mean age of 17 years and a moderate AIS (median Cobb Angle 18.2°) obtained low-dose standing biplanar radiographs with EOS. Two independent readers performed "full spine" 3D reconstructions of the spine with the "full-spine" method adjusting the bone contour of every thoracic and lumbar vertebra (Th1-L5). Interreader reproducibility was assessed regarding rotation of every single vertebra in the coronal (i.e. frontal), sagittal (i.e. lateral), and axial plane, T1/T12 kyphosis, T4/T12 kyphosis, L1/L5 lordosis, L1/S1 lordosis and pelvic parameters. Radiation exposure, scan-time and 3D reconstruction time were recorded. RESULTS: Interclass correlation (ICC) ranged between 0.83 and 0.98 for frontal vertebral rotation, between 0.94 and 0.99 for lateral vertebral rotation and between 0.51 and 0.88 for axial vertebral rotation. ICC was 0.92 for T1/T12 kyphosis, 0.95 for T4/T12 kyphosis, 0.90 for L1/L5 lordosis, 0.85 for L1/S1 lordosis, 0.97 for pelvic incidence, 0.96 for sacral slope, 0.98 for sagittal pelvic tilt and 0.94 for lateral pelvic tilt. The mean time for reconstruction was 14.9 minutes (reader 1: 14.6 minutes, reader 2: 15.2 minutes, p<0.0001). The mean total absorbed dose was 593.4µGy ±212.3 per patient. CONCLUSION: EOS "full spine" 3D angle measurement of vertebral rotation proved to be reliable and was performed in an acceptable reconstruction time. Interreader reproducibility of axial rotation was limited to some degree in the upper and middle thoracic spine due the obtuse angulation of the pedicles and the processi spinosi in the frontal view somewhat complicating their delineation.

Cervical esophagotomy for foreign body extraction - Case report and comprehensive review of the literature.

INTRODUCTION: Esophageal foreign bodies are an important and serious cause of morbidity and mortality in both children and adults. Due to the possibility of serious complications, i.e. perforation, necrosis, mediastinitis, and fistulation, rapid and accurate diagnostic measures with subsequent therapy are necessary. CASE REPORT: We are reporting a case of a 55-year-old, mentally impaired patient that has swallowed a foreign body, which subsequently became lodged in his esophagus. Due to the fact that endoscopic removal was not possible and there was a high risk of complications such as esophageal perforation or mediastinitis in this case, we performed cervical esophagotomy and successfully extracted the foreign body. The patient showed an uneventful postoperative process and could be discharged on Day 11 after the operation. COMPREHENSIVE REVIEW: Furthermore, we performed a systematic review of the literature to identify all studies that described a surgical approach through esophagotomy in cases of foreign body ingestion and found 11 publications describing the cases of 29 patients. These studies reported an overall complication rate of 17.2% and a mortality rate of 0%. CONCLUSION: Our findings suggest that esophagotomy could be a viable approach for the extraction of foreign bodies especially in some cases when endoscopic removal was not successful and the risk of esophageal perforation is high.

Epithelial-mesenchymal transition is a critical step in tumorgenesis of pancreatic neuroendocrine tumors.

The transcription factors Snail, Slug and Twist repress E-cadherin and induce epithelial-mesenchymal transition (EMT), a process exploited by invasive cancer cells. In this study, we evaluated the role of EMT in the tumorgenesis of neuroendocrine tumors of the pancreas (PNETs) in vitro, in vivo and human tumor specimen. Expression of EMT markers was analyzed using immunohistochemistry and real-time PCR. For in vitro studies, BON-1 cells were analyzed regarding expression of EMT markers before and after transfection with siRNA against Slug or Snail, and cell aggregation assays were performed. To asses in vivo effects, Rip1Tag2 mice were treated with vehicle or the snail-inhibitor polythlylenglykol from week 5-10 of age. The resected pancreata were evaluated by weight, tumor cell proliferation and apoptosis. Snail and Twist was expressed in 61 % and 64% of PNETs. This was associated with loss of E-cadherin. RT-PCR revealed conservation of the EMT markers Slug and Snail in BON-1 cells. Transfection with siRNA against Slug was associated with upregulation of E-cadherin, enhanced cell-cell adhesion and inhibition of cell proliferation. Snail-inhibition in vivo by PEG was associated with increased apoptosis, decreased tumor cell proliferation and dramatic reduced tumor volume in Rip1Tag2 mice. The presented data show that EMT plays a key role in tumorgenesis of PNETs. The activation of Snail in a considerable subset of human PNETs and the successful effect of Snail inhibition by PEG in islet cell tumors of transgenic mice provides first evidence of Snail as a drug target in PNETs.