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.

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.

This prospective study assessed the role of aminopyrine breath test in the prognosis of patients with cirrhosis, and evaluated whether the test provided useful information not included in the Pugh score. During a period of 36 months, 125 patients with biopsy proven liver cirrhosis were included, and followed for up to 48 months (median 17 months). During follow up 43 patients died (20 of liver failure). Survival was univariately related to aminopyrine breath test (p<002), Pugh score (p<0.01), presence of ascites (p<0.01), and sex (p<0.05). Using Cox's regression analysis, Pugh score, aminopyrine breath test, and sex, were independent significant predictors of survival. From the Cox's model a prognostic index was computed. According to a receiver operating characteristic curve analysis, the prognostic index predicting death showed an improvement in area under the curve when compared with a prognostic index calculated excluding aminopyrine breath test, but the improvement did not reach statistical significance (p=0.12). A similar prognostic index was calculated to predict death from liver failure. Cox's regression analysis selected aminopyrine breath test, Pugh score, and aetiology as the best set of predictor covariates. According to a receiver operating characteristic curve analysis, a prognostic index cut off value of 2-6 had a 94% sensitivity and a 88% specificity. The prognostic index significantly improved prognostic accuracy when compared with a prognostic index calculated from Pugh score and aetiology, but excluding aminopyrine breath test (p=0.05). These data disclose that the aminopyrine breath test offers additional prognostic information to the Pugh score, and it may become a useful tool to better assess the prognosis of patients with cirrhosis.

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.

Purpose Quinoline-based ligands targeting cancer-associated fibroblasts have emerged as promising radiopharmaceuticals in different tumor entities. The aim of this retrospective study was to explore the potential of FAPI-PET/CT in the initial staging of esophageal cancer patients and its usefulness in radiotherapy planning as a first clinical analysis. Methods Seven patients with treatment-naive esophageal cancer underwent FAPI-PET/CT. Tracer uptake was quantified by standardized uptake values (SUV)max and (SUV)mean. Six patients received definitive and one neoadjuvant (chemo)radiation therapy. Endo-esophageal clipping, the gold standard to define tumor margins not delineable per CT, was performed in three patients. Results Primary tumors demonstrated high FAPI uptake with a median SUVmax of 17.2. Excellent tumor-to-background ratios resulted in accurate target volume delineation and were found in perfect match with clipping. Detection of regional lymph node metastases facilitated the use of simultaneous integrated boost radiotherapy plans for these patients. Conclusion FAPI-PET/CT may be beneficial for the management of esophageal cancer particularly in planning radiotherapy, but further research is necessary to increase patient number and statistical reliability.

EoR, extent of resectionFLAIR, fluid-attenuated inversion recoveryGTR, gross total resectionIDH1, isocitrate dehydrogenase 1iMRI, intraoperative magnetic resonance imagingLGG, low-grade gliomaMGMT, methylguanine-deoxyribonucleic acid methyltransferasenPND, new permanent neurological deficitOS, overall survivalPFS, progression-free survivalSTR, subtotal resectionWHO, World Health Organization.

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 materialThe online version of this article (doi:10.1007/s11060-016-2362-z) contains supplementary material, which is available to authorized users.

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