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Background and Aims: Colorectal adenomas are precursor lesions for colorectal cancer (CRC), a major cause of cancer-related death. Despite all molecular insights, there are still unknown variables in the development of CRC as well as uncertainties regarding adenoma recurrence after resection. We aimed to characterize the expression of docking protein 1 (DOK1) and myotubularin-related protein 7 (MTMR7), which share inhibiting functions on EGFR-RAS-signalling, a major oncogenic driver in CRC, and their association with clinical variables and adenoma recurrence. Methods: This observational study is based on clinical data obtained from patients who underwent routine endoscopy and consecutive follow-up examinations. Immunohistochemistry was conducted both in dysplastic tissue and adjacent non-dysplastic mucosa followed by microscopical assessment. Recurrence was differentiated between local, segmental and distant relapse. Results: A total of 56 patients (23 females) gathering 96 adenomas/polyps were included. 36 patients experienced a metachronous lesion, 23 patients had simultaneous lesions in their index endoscopy. Female patients showed lower levels of MTMR7 in adenomas (p=0.0318). Adenomas of young patients showed lower DOK1 than those of older patients (p=0.0469). Big adenomas showed a higher expression of DOK1 than small lesions (p=0.0044). In serrated lesions, DOK1 was reduced (p=0.0026) and correlated with the quantity of lesions (p < 0.001). MTMR7 was significantly reduced in distant (p=0.05) and local segmental recurrence (p=0.0362), while DOK1 showed higher expression in recurrence (p=0.0291). Conclusions: We found ambivalent results regarding the role of the markers as potential tumor suppressors, implying a context-dependent function of these molecules which might change in the course of time. DOK1 may play an inhibiting role in the serrated pathway. Remarkably, molecular markers have the potential to predict recurrence, since a combined expression analysis of high DOK1 and low MTMR7 correlated with the likelihood of segmental adenoma recurrence.

Kreuzschmerzen sind weit verbreitet: Beinahe 80% aller Menschen leiden einmal in ihrem Leben unter einer Lumbalgie, die sie arbeitsunfahig macht. Aber wann wird es gefahrlich, und wann ist welche Therapie indiziert?

Uber die letzten Jahre zeigte sich innerhalb der deutschen Bevolkerung ein deutlicher Trend hin zum Ubergewicht. Durch technologischen Fortschritt nimmt die Zahl wirbelsaulenchirurgischer Eingriffe, insbesondere von Fusionsoperationen zu. Bei adiposen Patienten sollte man sich bei der Indikation und der Op.-Vorbereitung der spezifischen pra-, intra- und postoperativen Herausforderungen bewusst sein und darauf einstellen.

Prostate-specific membrane antigen (PSMA) PET/CT is a highly reliable nuclear tracer for diagnostic imaging of prostate cancer. However, PSMA is also expressed by some nonprostatic tissues such as benign tumors, inflammatory processes, and malignant neoplasms. This case presents a patient with prostate cancer and follicular lymphoma undergoing PSMA PET/CT. Remarkably, both tumor entities were clearly detected in the scan. Yet, the 2 malignancies demonstrated rather different ranges in terms of SUVmax uptake values and therefore still enabled precise and accurate discrimination of prostate cancer and follicular lymphoma.

// Elke Burgermeister 1,* , Patrick Hode 1,* , Johannes Betge 1 , Tobias Gutting 1 , Andreas Merkel 1 , Wen Wu 1 , Marc Tanzer 2 , Maximilian Mossner 3 , Daniel Nowak 3 , Julia Magdeburg 4 , Felix Ruckert 4 , Carsten Sticht 5 , Katja Breitkopf-Heinlein 1 , Nadine Schulte 1 , Nicolai Hartel 1 , Sebastian Belle 1 , Stefan Post 4 , Timo Gaiser 6 , Barbara Ingold Heppner 7 , Hans-Michael Behrens 8 , Christoph Rocken 8 and Matthias P.A. Ebert 1 1 Department of Medicine II, University Hospital Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany 2 Department of Medicine II, Klinikum rechts der Isar, Technische Universitat Munchen, Munich, Germany 3 Department of Medicine III, University Hospital Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany 4 Department of Surgery, University Hospital Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany 5 Center for Medical Research (ZMF), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany 6 Institute of Pathology, University Hospital Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany 7 Institute of Pathology, University Hospital Charite, Berlin, Germany 8 Institute of Pathology, Christian-Albrechts University, Kiel, Germany * These authors have contributed equally to this work Correspondence to: Matthias P.A. Ebert, email: // Keywords : TUSC3, colorectal cancer, prognosis, glycosylation, growth factor receptor Received : March 14, 2017 Accepted : August 23, 2017 Published : September 15, 2017 Abstract Colorectal cancer (CRC) is a biologically and clinically heterogeneous disease. Even though many recurrent genomic alterations have been identified that may characterize distinct subgroups, their biological impact and clinical significance as prognostic indicators remain to be defined. The tumor suppressor candidate-3 ( TUSC3/N33 ) locates to a genomic region frequently deleted or silenced in cancers. TUSC3 is a subunit of the oligosaccharyltransferase (OST) complex at the endoplasmic reticulum (ER) which catalyzes bulk N-glycosylation of membrane and secretory proteins. However, the consequences of TUSC3 loss are largely unknown. Thus, the aim of the study was to characterize the functional and clinical relevance of TUSC3 expression in CRC patients’ tissues ( n =306 cases) and cell lines. TUSC3 mRNA expression was silenced by promoter methylation in 85 % of benign adenomas ( n =46 cases) and 35 % of CRCs ( n =74 cases). Epidermal growth factor receptor (EGFR) was selected as one exemplary ER-derived target protein of TUSC3-mediated posttranslational modification. We found that TUSC3 inhibited EGFR-signaling and promoted apoptosis in human CRC cells, whereas TUSC3 siRNA knock-down increased EGFR-signaling. Accordingly, in stage I/II node negative CRC patients ( n =156 cases) loss of TUSC3 protein expression was associated with poor overall survival. In sum, our data suggested that epigenetic silencing of TUSC3 may be useful as a molecular marker for progression of early CRC.

Objective Tissue oxygen tension is an important parameter for brain tissue viability and its noninvasive intraoperative monitoring in the whole brain is of highly clinical relevance. The purpose of this study was the introduction of a multiparametric quantitative blood oxygenation dependent magnetic resonance imaging (MRI) approach for intraoperative examination of oxygen metabolism during the resection of brain lesions. Methods Sixteen patients suffering from brain lesions were examined intraoperatively twice (before craniotomy and after gross-total resection) via the quantitative blood oxygenation dependent technique and a 1.5-Tesla MRI scanner, which is installed in an operating room. The MRI protocol included T2*- and T2 mapping and dynamic susceptibility weighted perfusion. Data analysis was performed with a custom-made, in-house MatLab software for calculation of maps of oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO 2 ) as well as of cerebral blood volume and cerebral blood flow. Results Perilesional edema showed a significant increase in both perfusion (cerebral blood volume +21%, cerebral blood flow +13%) and oxygen metabolism (OEF +32%, CMRO 2 +16%) after resection of the lesions. In perilesional nonedematous tissue only, however, oxygen metabolism (OEF +19%, CMRO 2 +11%) was significantly increased, but not perfusion. No changes were found in normal brain. Fortunately, no neurovascular adverse events were observed. Conclusions This approach for intraoperative examination of oxygen metabolism in the whole brain is a new application of intraoperative MRI additionally to resection control (residual tumor detection) and updating of neuronavigation (brain shift detection). It may help to detect neurovascular adverse events early during surgery.

Nackenschmerzen bzw. Schmerzen im Schulter-Nackenbereich sind im klinischen Alltag haufig. In diesem Beitrag werden schnell und effizient nutzbare Untersuchungsmoglichkeiten beschrieben, die eine Differenzierung der Beschwerden nach deren Ursache erleichtern und darauf folgend eine stufenweise effektive — bildgebende — Diagnostik bahnen.

Sind alle konservativen Therapieoptionen ausgeschopft und die Indikation gesichert, sollte man geriatrischen Patienten trotz des hoheren Komplikationsrisikos eine Wirbelsaulenoperation nicht verwehren. Wichtig ist, die besonderen Risiken durch das Alter und Komorbiditaten in der perioperativen Betreuung zu berucksichtigen.

Objective Various complex techniques for depth electrode insertion in refractory epilepsy using preoperative imaging have been investigated. We evaluated a simple, accurate, cost-effective, and timesaving method using intraoperative magnetic resonance imaging (MRI). Methods A neuronavigation-guided insertion tube attached to bone facilitated the placement of stereotactic percutaneous drill holes, bolt implantation, and frameless stereotactic insertion of depth electrodes. Image registration was carried out by head coil fiducials with trajectory planning and intraoperative electrode correction. Results In 6 patients with refractory epilepsy (3 women and 3 men; mean age, 30.0 years; range, 20–37 years), 58 depth electrodes (9–11 per patient) were placed. The mean length of the inserted electrodes was 37.3 mm ± 8.8 (mean ± SD) (range, 22.1–84.4 mm). The overall target point accuracy was 3.2 mm ± 2.2 (range, 0–8.6 mm), which was significantly different from the overall entry point accuracy of 1.4 mm ± 1.2 ( P Conclusions Our frameless technique of depth electrode insertion using intraoperative MRI guidance is an accurate, reliable, cost-effective, and timesaving method for stereo-electroencephalography.

Auch bei geriatrischen Patienten gibt es klare Indikationen, die fur eine Wirbelsaulenoperation sprechen. Neben anasthesie- und operationsbedingten Gefahren mussen dabei aber auch die besonderen Risiken im Alter und Komorbiditaten berucksichtigt und abgewogen werden.

Die intraoperative MRT-Bildgebung in der Gliomchirurgie ist auch mehr als 20 Jahre nach ihrer erstmaligen Einfuhrung eine ganz wesentliche Hilfe zur Verbesserung des Resektionsausmases. Die moglichst vollstandige Resektion von Gliomen bildete nach wie vor den ersten und entscheiden Schritt in der Therapie, trotz aller Fortschritte in Radioonkologie, medikamentoser und Immuntherapie. Die Radikalitat der Resektion soll jedoch nicht zulasten der neurologischen Funktion des Patienten gehen. Ein Zurucklassen prinzipiell resektabler Tumoranteile verschlechtert nach heutiger Auffassung das Langzeitergebnis des Eingriffs. Die MRT-Bildgebung wurde daher als logischer Schritt Anfang der 1990er Jahre in das operative Verfahren integriert. Seitdem wurde sie bestandig weiter entwickelt. Die Verbesserung des Resektionausmases ist durch zahlreiche Studien fur Niederfeld- wie fur Hochfeldsysteme belegt, in letzter Zeit fur 3-Tesla-Systeme. Das Kapitel zeigt den Stellenwert der intraoperativen Bildgebung in der Gliomchirurgie auf, geht aber auch auf Probleme ein und teilt mit potenziellen Anwendern praktische Erfahrung, die uber ein Jahrzehnt gesammelt wurde.

The benefit of the sitting position for surgery of the posterior fossa and cervical spine is still a matter of controversy. In our study we analyzed the outcome after sitting position surgery at our institution. We compared the incidence of venous air embolism (VAE) as recognized with different monitoring techniques and the severity of complications. We retrospectively analyzed 600 patients, who underwent surgery for different posterior fossa and cervical spine pathologies, respectively, in the sitting position at our institution from 1995 to 2011. Intraoperative monitoring for VAE included endtidal CO2 level, Doppler ultrasound or intraoperative transesophageal echocardiography (TEE). We defined VAE as a decrease of the endtidal CO2 levels by more than 4 mm Hg, a characteristic sound in the thoracic Doppler, or any sign of air in the TEE. We found an overall incidence of VAE in 19 % of all patients, whereas the rate of severe complications associated with VAE such as a decline of partial oxygen pressure (pO2) or a drop of blood pressure was only 3.3 % in all patients. Only three out of 600 operations had to be terminated because of non-controllable VAE (0.5 %). There was no mortality resulting from VAE in our series. We also found a difference in the incidence of VAE depending on the monitoring technique. The VAE rate as monitored with TEE was 25.6 % whereas the incidence of VAE in patients monitored with Doppler ultrasound was 9.4 %. The rate of a significant VAE was comparable in both methods 4.8 % vs. 1.2 %. All patients were preoperatively screened for persisting foramen ovale (PFO); 24 patients with clinically confirmed PFO were included in this series. There was no case of paradox air embolism. In our series, VAE was detected in 19 % of all patients in the sitting position. However, in only 0.5 % of cases a termination of the surgical procedure became necessary. In all other cases, the cause of air embolism could be found and eliminated during surgery. TEE was found to be the monitoring technique with the highest sensitivity. In our opinion, the sitting position is a safe positioning technique if TEE monitoring is used.

Molecular markers define the diagnosis of glioblastoma in the new WHO classification of 2016, challenging neuro-oncology centers to provide timely treatment initiation. The aim of this study was to determine whether a time delay to treatment initiation was accompanied by signs of early tumor progression in an MRI before the start of radiotherapy, and, if so, whether this influences the survival of glioblastoma patients. Images from 61 patients with early post-surgery MRI and a second MRI just before the start of radiotherapy were examined retrospectively for signs of early tumor progression. Survival information was analyzed using the Kaplan–Meier method, and a Cox multivariate analysis was performed to identify independent variables for survival prediction. 59 percent of patients showed signs of early tumor progression after a mean time of 24.1 days from the early post-surgery MRI to the start of radiotherapy. Compared to the group without signs of early tumor progression, which had a mean time of 23.3 days (p = 0.685, Student’s t test), progression free survival was reduced from 320 to 185 days (HR 2.3; CI 95% 1.3–4.0; p = 0.0042, log-rank test) and overall survival from 778 to 329 days (HR 2.9; CI 95% 1.6–5.1; p = 0.0005). A multivariate Cox regression analysis revealed that the Karnofsky performance score, O-6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation, and signs of early tumor progression are prognostic markers of overall survival. Early tumor progression at the start of radiotherapy is associated with a worse prognosis for glioblastoma patients. A standardized baseline MRI might allow for better patient stratification. Electronic supplementary material The online version of this article (doi:10.1007/s11060-016-2362-z) contains supplementary material, which is available to authorized users.

Safe and complete resection represents the first step in the treatment of glioblastomas and is mandatory in increasing the effectiveness of adjuvant therapy to prolong overall survival. With gross total resection currently limited in extent to MRI contrast enhancing areas, the extent to which supra-complete resection beyond obvious contrast enhancement could have impact on overall survival remains unclear. DiVA (dual intraoperative visualization approach) redefines gross total resection as currently accepted by enabling for the first time supra-complete surgery without compromising patient safety. This approach exploits the advantages of two already accepted surgical techniques combining intraoperative MRI with integrated functional neuronavigation and 5-ALA by integrating them into a single surgical approach. We investigated whether this technique has impact on overall outcome in GBM patients. 105 patients with GBM were included. We achieved complete resection with intraoperative MRI alone according to current best-practice in glioma surgery in 75 patients. 30 patients received surgery with supra-complete resection. The control arm showed a median life expectancy of 14 months, reflecting current standards-of-care and outcome. In contrast, patients receiving supra-complete surgery displayed significant increase in median survival time to 18.5 months with overall survival time correlating directly with extent of supra-complete resection. This extension of overall survival did not come at the cost of neurological deterioration. We show for the first time that supra-complete glioma surgery leads to significant prolongation of overall survival time in GBM patients.

Despite advances in multimodal treatments, malignant gliomas remain characterized by a short survival time. Surgical treatment is accepted to be the first line of therapy, with recent studies revealing that maximal possible tumor reduction exerts significant impact on patient outcome. Consideration of tumor localization in relation to functionally eloquent brain areas has been gaining increasing importance. Despite existing assessment methods, the availability of a simple but reliable preoperative grading based on functional data would therefore prove to be indispensable for the prediction of postoperative outcome and hence for overall survival in glioma patients. We performed a clinical investigation comprising 322 patients with gliomas and developed a novel classification system of preoperative tumor status, which considers tumor operability based on two graduations (Friedlein Grading - FG): FGA with lesions at safe distance to eloquent regions which can be completely resected and FGB referring to tumors which can only be partially resected or biopsied. Investigation of outcome revealed that FGA were characterized by a significantly longer overall survival time compared to FGB. We offer the opportunity to classify brain tumors in a dependable and reproducible manner. The FGA/B grading method provides high prognostic value with respect to overall survival time in relation to the extent of location-dependent tumor resection.

2036 Background: As recently demonstrated (Neurooncology, 2016), neurological decline of patients with brain cancer (high grade glioma, brain metastases) during radio(chemo)therapy (RCT) of the brain is oftentimes caused by CMV-encephalopathy but not disease progression or therapeutic complications. We examined the impact of clinical and serological CMV-status on the survival one year after the onset of radio(chemo)therapy of the brain. Methods: 118 patients requiring whole-brain radiotherapy for brain metastases (n = 55) or local RCT of the brain for high-grade gliomas (n = 63) were observed in the prospective GLIO-CMV-01 study. MRIs and blood samples were obtained before, halfway through, and at the end of radiotherapy. MRIs were screened for disease progression or increased intracranial pressure. Blood was tested for anti-CMV immunoglobulin (Ig)M, anti-CMV IgG, and CMV DNA. Results: 68 of 118 (58%) patients were positive for anti-CMV IgG before radio(chemo)therapy. 28 of those 68 (41%) developed CMV-viremia during or up to 28 days after the end of irradiation. 21 of those 28 (75%) required treatment for symptomatic CMV-associated encephalopathy. One year after the start of RCT, survival was 72% (34/47) (no encephalopathy, anti-CMV-IgG+) or 68% (34/50) (no encephalopathy, anti-CMV-IgG-) versus 38% (8/21) (encephalopathy) (p = 0.0034). Conclusions: Symptomatic CMV-encephalopathy all but doubles the mortality of brain cancer patients within one year of RCT, despite antiviral treatment with ganciclovir. These findings heavily underline the importance to identify patients with increased risk profile for developing CMV-encephalopathy before initiating RCT.

Malignant gliomas belong to the most threatening tumor entities and are hallmarked by rapid proliferation, hypervascularization and an invasive growth pattern. The primary obstacle in surgical treatment lies in differentiation between healthy and pathological tissue at the tumor margins, where current visualization methods reach their limits. Here, we report on a novel technique (vascular dual intraoperative visualization approach - vDIVA) enabling visualization of different tumor zones (TZ I–III) on the basis of angiogenic hotspots. We investigated glioblastoma patients who underwent 5-ALA fluorescence-guided surgery with simultaneous intraoperative ICG fluorescence angiography. This vDIVA technique revealed hypervascularized areas which were further histologically investigated. Neuropathological assessments revealed tissue areas at the resection margins corresponding to TZ II and postoperative CD34- and Map2 immunostaining confirmed these angiogenic hotspots to be occupied by glioma cells. Hence, the vascular architecture in this transitional zone could be well differentiated from both primary tumor bulk and healthy brain parenchyma. These data demonstrate that ICG fluorescence angiography improves state-of-the-art glioma surgery techniques and facilitates the future characterization of polyclonal attributes of malignant gliomas.

Cloud Computing and Web 2.0 technologies not only led to simplification of a variety of World Wide Web services but also contribute to a vast diversity of complex internet applications. The purpose of this paper is to find out: ?How can an SME act and get information in an innovative environment of networked partners by using web technologies?? This paper presents a case study designed with a combination of the research methods: expert interviews, data analyses and trans-disciplinary workshops including group discussion. The findings of this research base a theoretical description of the dimension of innovation of the investigated SME network. Different levels of innovation with diverse drivers and types of innovation are explored. Requirements, possibilities and obstacles for Cloud Computing and Web 2.0 technology implementations for this network are uncovered. These qualitative findings result in the development of concepts for innovative web applications regarding cooperation improvement and knowledge diffusion.