Does an Analysis of the Pulsatile Secretion Pattern of Adrenocorticotropin and Cortisol Predict the Result of Transsphenoidal Surgery in Cushing’s Disease.

The endocrinological, surgical, and histological findings of patients with ACTH-dependent Cushing's disease were correlated with the pulsatile secretion pattern of ACTH and cortisol and the outcome after transsphenoidal pituitary surgery. A total of 28 patients were studied. The preoperative pulsatile secretion of ACTH and cortisol was assessed by sampling blood at 20-min intervals over 24 h. The pulsatile pattern of secretion was analyzed by the Cluster program. In 21 patients, an ACTH-secreting pituitary adenoma was identified and resected. Of these patients, 18 underwent clinical remission, and their cortisol secretion was suppressed to a normal level by low dose dexamethasone. Histological examinations in the patients with persistent disease revealed normal pituitary in 6 cases, nodular hyperplasia in 1, and ACTH-secreting pituitary adenoma in 3 cases. Analysis of the pulsatile pattern of ACTH and cortisol secretion did not reveal significant differences in timing, frequency, and/or amplitude of ACTH and cortisol pulses in normalized patients and those with persistent disease after surgery. It is concluded that analysis of the secretory pattern is not a suitable method for predicting the outcome of ranssphenoidal surgery in patients with ACTH-dependent Cushing's disease

Comparing 1.5 T and 3.0 T MR data for 3D visualization of neurovascular relationships in the posterior fossa

Background Neurovascular relationships in the posterior fossa are more frequently investigated due to the increasing availability of 3.0 Tesla MRI. For an assessment with 3D visualization, no systematic analyzes are available so far and the question arises as to whether 3.0 Tesla MRI should be given preference over 1.5 Tesla MRI. Methods In a prospective study, a series of 25 patients each underwent MRI investigations with 3D-CISS and 3D-TOF at 1.5 and 3.0 Tesla. For both field strengths separately, blood vessel information from the TOF data was fused into the CISS data after segmentation and registration. Four visualizations were created for each field strength, with and without optimization before and after fusion, which were evaluated with a rating system and verified with the intraoperative situation. Results When only CISS data was used, nerves and vessels were better visualized at 1.5 Tesla. After fusion, flow and pulsation artifacts were reduced in both cases, missing vessel sections were supplemented at 3.0 Tesla and 3D visualization at 1.5 and 3.0 Tesla led to anatomically comparable results. By subsequent manual correction, the remaining artifacts were further eliminated, with the 3D visualization being significantly better at 3.0 Tesla, since the higher field strength led to sharper contours of small vessel and nerve structures. Conclusion 3D visualizations at 1.5 Tesla are sufficiently detailed for planning microvascular decompression and can be used without restriction. Fusion further improves the quality of 3D visualization at 3.0 Tesla and enables an even more accurate delineation of cranial nerves and vessels.Open Access funding enabled and organized by Projekt DEAL.Universitätsklinikum Erlangen (8546

Tight junction protein claudin-1 is differentially expressed in craniopharyngioma subtypes and indicates invasive tumor growth

Background: Claudins are tight junction proteins expressed in epithelial tissues that play important roles in cell polarity and adhesion. Altered distribution of claudin-1(CLDN1) affects cell mobility and tumor invasiveness. Craniopharyngiomas (CPs) represent epithelial tumors of the sellar region, consisting of adamantinomatous (adaCP) and papillary (papCP) variants. Their tendency to infiltrate surrounding brain structures complicates successful surgery. Reliable markers are required to predict tumor behavior and to establish individualized treatment protocols. Methods: We describe the distribution pattern of CLDN1 in a large cohort of 66 adaCPs, 21 papCPs, and 24 Rathke`s cleft cyst (RCC) cases using immunohistochemistry. CLDN1 mRNA levels were analyzed with qRT-PCR in 33 CP samples. The impact on the migration potential was studied in primary adaCP cell cultures (n = 11) treated with small interfering RNA (siRNA) for CLDN1. Furthermore, CLDN1 distribution patterns and expression levels were compared between invasive (n = 16) and noninvasive (n = 17) tumor groups. Results: PapCPs and RCCs exhibited a distinct homogenous and membranous expression pattern, whereas CLDN1 immunoreactivity appeared weaker and more heterogeneous in adaCPs. In the latter cases, whirl-like cell clusters showed complete absence of CLDN1. mRNA analysis confirmed reduced CLDN1 levels in adaCPs versus papCPs. Interestingly, invasive tumors exhibited significantly lower CLDN1 expression compared with noninvasive counterparts regardless of CP subtype. Accordingly, siRNA treatment for CLDN1 altered tumor cell migration in vitro. Conclusion: CLDN1 represents a novel marker in the differential diagnosis of CP variants and RCCs. Low CLDN1 expression levels correlate with an invasive CP growth pattern and may serve as a prognostic marker

3D-Visualization of Neurovascular Compression at the Ventrolateral Medulla in Patients with Arterial Hypertension

Purpose Controversy exists on the association of arterial hypertension (HTN) and neurovascular compression (NVC) at the ventrolateral medulla (VLM). No standardized and reproducible technique has been introduced yet for detection of NVC in HTN. This study aimed to generate, analyze and compare different results of exact reproducible anatomical 3D-representations of the VLM in patients with HTN, based on magnetic resonance imaging (MRI). Methods A 3T scanner provided MRI (T2-constructive interference in steady state (CISS) high resolution imaging and three-dimensional Time-of-flight (3D-TOF) angiography) from the posterior fossa of 44 patients with clinical treatment-resistant HTN. Image processing consists of segmentation of the CISS data, registration and fusion of the CISS and TOF data and visualization. For each patient two 3D-visualizations (before and after fusion) were obtained. The reproduction quality of the vessels, flow-related signal variability and pulsation artifacts were analyzed and compared, using a ranking score. Results Integrating vascular information from TOF into CISS data reduced artifacts in 3D-visualizations of exclusively processed CISS data. The quality of 3D-visualization of the vessels near the brain stem was significantly improved (p = 0.004). The results were reproducible and reliable. The quality of the 3D-presentations of neurovascular relationships at the VLM improved significantly (p < 0.001). Conclusion The 3D-visualization of fused image data provides an excellent overview of the relationship between cranial nerves and vessels at the VLM and simplifies the detection of NVC in HTN. It provides a powerful tool for future clinical and scientific research. Although microvascular decompression (MVD) in treatment resistant HTN is not a standard procedure, it can be discussed in selected patients with intractable severe HTN

Multiple tumorous lesions of the pituitary gland

Purpose/Objective Multiple tumorous lesions in one pituitary gland are rare and mostly described in case reports. Their incidences and combinations are defined in larger collectives. Therefore, we analyzed our large collection for double tumors and combinations of tumors, cysts, and inflammation. Methods The German Registry of Pituitary Tumors, including cases from 1990 to 2018, served as the database. Our collection comprises a total of 16,283 cases up until the end of 2018. Of these cases, 12,673 originated from surgical and 3,610 from autopsy material. All specimens were fixed in formalin and embedded in paraffin. The sections were stained with hematoxylin–eosin and PAS. Monoclonal (prolactin, TSH, FSH, LH, and α subunit) or polyclonal (GH and ACTH) antibodies were used to detect pituitary hormones in the lesions. Since 2017, antibodies against the transcription factors Pit-1, T-Pit, and SF-1 have been used in difficult cases. The criteria of the 2017 WHO classification have been basic principles for classification since 2018 (Osamura et al. 2 ). For differentiation of other sellar tumors, such as meningiomas, chordomas, or metastases, the use of additional antibodies was necessary. For these cases, it was possible to use a broad antibody spectrum. Autopsy pituitaries were generally studied by H&E and PAS sections. If any lesions were demonstrated in these specimens, additional immunostaining was performed. Results Multiple tumorous lesions with more than one pituitary neuroendocrine tumor (PitNET) respectively adenoma make up 1.4% (232 cases) in our collection. Within the selected cases, synchronous multiple pituitary neuroendocrine tumors (PitNETs) account for 17.3%, PANCH cases (pituitary adenoma with neuronal choristoma) for 14.7%, PitNETs and posterior lobe tumors for 2.2%, PitNETs and metastases for 5.2%, PitNETs and mesenchymal tumors for 2.6%, PitNETs and cysts for 52.2%, and PitNETs and primary inflammation for 6.0%. The mean patient age was 53.8 years, with a standard deviation of 18.5 years. A total of 55.3% of the patients were female and 44.7% were male. From 1990 to 2018, there was a continuous increase in the number of multiple tumorous lesions. Conclusion From our studies, we conclude that considering possible tumorous double lesions during surgeries and in preoperative X-ray analyses is recommended.Open Access funding enabled and organized by Projekt DEAL.Ipsen PharmaNovartis Pharma http://dx.doi.org/10.13039/100008792Novo Nordisk http://dx.doi.org/10.13039/501100004191Pfizer http://dx.doi.org/10.13039/100004319Universitätsklinikum Hamburg-Eppendorf (UKE) (5411

Adamantinomatous and papillary craniopharyngiomas are characterized by distinct epigenomic as well as mutational and transcriptomic profiles

Introduction Craniopharyngiomas (CP) are rare epithelial tumors of the sellar region. Two subtypes, adamantinomatous (adaCP) and papillary CP (papCP), were previously identified based on histomorphological and epidemiological aspects. Recent data indicates that both variants are defined by specific genetic alterations, and influenced by distinct molecular pathways and particular origins. The fact that CP is an uncommon tumor entity renders studies on large cohorts difficult and exceptional. In order to achieve further insights distinguishing CP variants, we conducted whole genome methylation (450 k array) and microarray-based gene expression studies in addition to CTNNB1 and BRAF mutation analysis using a comprehensive cohort of 80 adaCP and 35 papCP. Results BRAF V600E mutations were solely found in the papCP subgroup and were not detectable in adaCP samples. In contrast, CTNNB1 mutations were exclusively detected in adaCP. The methylome fingerprints assigned DNA specimens to entity-specific groups (papCP (n = 18); adaCP (n = 25)) matching perfectly with histology-based diagnosis, suggesting that they represent truly distinct biological entities. However, we were not able to detect within the adaCP group (including 11 pediatric and 14 adult cases) a significant difference in methylation signature by age. Integrative comparison of the papCP with the adaCP group based on differential gene expression and methylation revealed a distinct upregulation of Wnt- and SHH signaling pathway genes in adaCP. Conclusions AdaCP and papCP thus represent distinct tumor subtypes that harbor mutually exclusive gene mutations and methylation patterns, further reflected in differences in gene expression. This study demonstrates that DNA methylation analyses are an additional method to classify CP into subtypes, and implicates a role of epigenetic mechanisms in the genesis of the respective CP variants. Detection of tumor-specific signaling pathway activation enables the possibility of target-oriented intervention

Introduction: Utility of intraoperative imaging

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Visualization strategies for major white matter tracts identified by diffusion tensor imaging for intraoperative use

Streamline representation of major fiber tract systems along with high-resolution anatomical data provides a reliable orientation for the neurosurgeon. For direct visualization of these data in the surgical field applying heads-up displays of operating microscopes, wrapping of all streamlines of interest to render an individual object representing the whole fiber bundle is mandatory. Integration of fiber tract data into a neuronavigation setup allows removal of tumors adjacent to eloquent brain areas with low morbidity

Directional volume growing for the extraction of white matter tracts from diffusion tensor data

Diffusion tensor imaging measures diffusion of water in tissue. Within structured tissue, such as neural fiber tracts of the human brain, anisotropic diffusion is observed since the cell membranes of the long cylindric nerves restrict diffusion. Diffusion tensor imaging thus provides information about neural fiber tracts within the human brain which is of major interest for neurosurgery. However, the visualization is a challenging task due to noise and limited resolution of the data. A common visualization strategy of white matter is fiber tracking which utilizes techniques known from flow visualization. The resulting streamlines provide a good impression of the spatial relation of fibers and anatomy. Therefore, they are a valuable supplement for neurosurgical planning. As a drawback, fibers may diverge from the exact path due to numerical inaccuracies during streamline propagation even if higher order integration is used. To overcome this problem, a novel strategy for directional volume growing is presented which enables the extraction of separate tract systems and thus allows to compare and estimate the quality of fiber tracking algorithms. Furthermore, the presented approach is suited to get a more precise representation of the volume encompassing white matter tracts. Thereby, the entire volume potentially containing fibers is provided in contrast to fiber tracking which only shows a more restricted representation of the actual volume of interest. This is of major importance in brain tumor cases where white matter tracts are in the close vicinity of brain tumors. Overall, the presented strategy contributes to make surgical planning safer and more reliable