Intracranial Germinomas: Diagnosis, Pathogenesis, Clinical Presentation, and Management.

PURPOSE OF REVIEW: Intracranial germinomas constitute a rare brain tumor entity of unknown etiology, characterized by unique histopathology and molecular biology. In this manuscript, we review the literature focusing on the epidemiology, histopathology with molecular biology, clinical presentation with emphasis on tumor location, diagnostic workup, and current treatment strategies with related clinical outcomes of intracranial germinomas. RECENT FINDINGS: Although the optimal treatment strategy remains a matter of debate, intracranial germinomas respond well to radiotherapy, chemotherapy, or a combination of both and are characterized by very high cure and survival rates. It is well-known that early discrimination of germinomas from other intracranial neoplasms facilitates the timely initiation of appropriate treatment, thereby contributing to the reduction of morbidity as well as mortality. Ongoing research will need to be directed towards discovering and refining reliable parameters for early diagnosis and evaluation of prognosis in patients with intracranial germinomas.

Ultra-High-Field 7 T Magnetic Resonance Imaging Including Dynamic and Static Contrast-Enhanced T1-Weighted Imaging Improves Detection of Secreting Pituitary Microadenomas.

OBJECTIVE: A prospective preoperative evaluation of 7 T ultra-high-field magnetic resonance imaging (MRI) in patients with suspected pituitary microadenomas for both adenoma detection and intrasellar localization compared with 3 T MRI was carried out. MATERIALS AND METHODS: Patients underwent prospective preoperative standardized 3 and 7 T MRI. A distinct qualitative (lesion detection, intrasellar lesion location) and quantitative (lesion diameters, T1/T2 signal intensity ratio of the lesion to normal pituitary gland tissue) analysis was performed, along with an evaluation of image quality (IQ) regarding overall IQ, anatomical parameters, and artifacts; the findings of the qualitative analysis were compared with intraoperative findings and endocrinological outcomes. RESULTS: Sixteen patients (mean age, 43 ± 16 years; 13 women) with pituitary microadenomas were included. Using 7 T MRI allowed the detection of 15 microadenomas-3 more than 3 T MRI. In addition, 7 T MRI allowed more precise lesion localization with 93.75% (15/16) agreement with intraoperative findings, compared with 75% (12/16) agreement using 3 T MRI. Lesion diameters showed no significant difference between 3 and 7 T MRI. T1 and T2 signal intensity ratio between microadenomas and normal pituitary gland tissue were higher in 7 T MRI than in 3 T MRI. The overall IQ and the IQ of each anatomical parameter of 7 T MRI were rated higher than those of 3 T MRI. No significant differences in susceptibility or head motion artifacts were observed between 3 and 7 T MRI; however, 7 T MRI was more susceptible to pulsation artifacts. CONCLUSION: Ultra-high-field MRI surpasses 3 T MRI in pituitary microadenoma detection and enables more precise delineation with higher correlation with intraoperative findings. Thus, 7 T sellar imaging is a promising option-especially in previously magnetic resonance-negative patients with endocrinologically confirmed hormone oversecretion-and helps reduce the need for invasive diagnostics.

Physiological MRI of microvascular architecture, neovascularization activity, and oxygen metabolism facilitate early recurrence detection in patients with IDH-mutant WHO grade 3 glioma.

PURPOSE: This study aimed to determine the diagnostic performance of physiological MRI biomarkers including microvascular perfusion and architecture, neovascularization activity, tissue oxygen metabolism, and tension for recurrence detection of IDH-mutant WHO grade 3 glioma. METHODS: Sixty patients with IDH-mutant WHO grade 3 glioma who received overall 288 follow-up MRI examinations at 3 Tesla after standard treatment were retrospectively evaluated. A conventional MRI protocol was extended with a physiological MRI approach including vascular architecture mapping and quantitative blood-oxygen-level-dependent imaging which required 7 min extra data acquisition time. Custom-made MATLAB software was used for the calculation of MRI biomarker maps of microvascular perfusion and architecture, neovascularization activity, tissue oxygen metabolism, and tension. Statistical procedures included receiver operating characteristic analysis. RESULTS: Overall, 34 patients showed recurrence of the WHO grade 3 glioma; of these, in 15 patients, recurrence was detected one follow-up examination (averaged 160 days) earlier by physiological MRI data than by conventional MRI. During this time period, the tumor volume increased significantly (P = 0.001) on average 7.4-fold from 1.5 to 11.1 cm3. Quantitative analysis of MRI biomarkers demonstrated microvascular but no macrovascular hyperperfusion in early recurrence. Neovascularization activity (AUC = 0.833), microvascular perfusion (0.682), and oxygen metabolism (0.661) showed higher diagnostic performance for early recurrence detection of WHO grade 3 glioma compared to conventional MRI including cerebral blood volume (0.649). CONCLUSION: This study demonstrated that the targeted assessment of microvascular features and tissue oxygen tension as an early sign of neovascularization activity provided valuable information for recurrence diagnostic of WHO grade 3 glioma.

Bariatric Surgery for Hypothalamic Obesity in Craniopharyngioma Patients: A Retrospective, Matched Case-Control Study.

CONTEXT: Craniopharyngioma is a sellar tumor associated with high rates of pituitary deficiencies (~ 98%) and hypothalamic obesity (~ 50%). OBJECTIVE: This work aims to determine the efficacy regarding long-term weight loss after bariatric surgery in obese craniopharyngioma patients with hypothalamic dysfunction. METHODS: This retrospective, case-control, multicenter, international study included obese craniopharyngioma patients (N = 16; of whom 12 are women) with a history of bariatric surgery (12 Roux-en-Y gastric bypass, 4 sleeve gastrectomy; median age 21 years [range, 15-52 years], median follow-up 5.2 years [range, 2.0-11.3 years]) and age/sex/surgery/body mass index-matched obese controls (N = 155). Weight loss and obesity-related comorbidities up to 5 years after bariatric surgery were compared and changes in hormonal replacement therapy evaluated. RESULTS: Mean weight loss at 5-year follow-up was 22.0% (95% CI, 16.1%-27.8%) in patients vs 29.5% (95% CI, 28.0%-30.9%) in controls (P = .02), which was less after Roux-en-Y gastric bypass (22.7% [16.9%-28.5%] vs 32.0% [30.4%-33.6%]; P = .003) but at a similar level after sleeve gastrectomy (21.7% [-1.8% to 45.2%] vs 21.8% [18.2%-25.5%]; P = .96). No major changes in endocrine replacement therapy were observed after surgery. One patient died (unknown cause). One patient had long-term absorptive problems. CONCLUSION: Obese patients with craniopharyngioma had a substantial mean weight loss of 22% at 5-year follow-up after bariatric surgery, independent of type of bariatric surgery procedure. Weight loss was lower than in obese controls after Roux-en-Y gastric bypass. Bariatric surgery appears to be effective and relatively safe in the treatment of obese craniopharyngioma patients.

Hypoxia and Microvascular Alterations Are Early Predictors of IDH-Mutated Anaplastic Glioma Recurrence.

Anaplastic gliomas (AG) represents aggressive brain tumors that often affect young adults. Although isocitrate-dehydrogenase (IDH) gene mutation has been identified as a more favorable prognostic factor, most IDH-mutated AG patients are confronted with tumor recurrence. Hence, increased knowledge about pathophysiological precursors of AG recurrence is urgently needed in order to develop precise diagnostic monitoring and tailored therapeutic approaches. In this study, 142 physiological magnetic resonance imaging (phyMRI) follow-up examinations in 60 AG patients after standard therapy were evaluated and magnetic resonance imaging (MRI) biomarker maps for microvascular architecture and perfusion, neovascularization activity, oxygen metabolism, and hypoxia calculated. From these 60 patients, 34 patients developed recurrence of the AG, and 26 patients showed no signs for AG recurrence during the study period. The time courses of MRI biomarker changes were analyzed regarding early pathophysiological alterations over a one-year period before radiological AG recurrence or a one-year period of stable disease for patients without recurrence, respectively. We detected intensifying local tissue hypoxia 250 days prior to radiological recurrence which initiated upregulation of neovascularization activity 50 to 70 days later. These changes were associated with a switch from an avascular infiltrative to a vascularized proliferative phenotype of the tumor cells another 30 days later. The dynamic changes of blood perfusion, microvessel density, neovascularization activity, and oxygen metabolism showed a close physiological interplay in the one-year period prior to radiological recurrence of IDH-mutated AG. These findings may path the wave for implementing both new MR-based imaging modalities for routine follow-up monitoring of AG patients after standard therapy and furthermore may support the development of novel, tailored therapy options in recurrent AG.

Physiological MRI Biomarkers in the Differentiation Between Glioblastomas and Solitary Brain Metastases.

PURPOSE: Glioblastomas (GB) and solitary brain metastases (BM) are the most common brain tumors in adults. GB and BM may appear similar in conventional magnetic resonance imaging (cMRI). Their management strategies, however, are quite different with significant consequences on clinical outcome. The aim of this study was to evaluate the usefulness of a previously presented physiological MRI approach scoping to obtain quantitative information about microvascular architecture and perfusion, neovascularization activity, and oxygen metabolism to differentiate GB from BM. PROCEDURES: Thirty-three consecutive patients with newly diagnosed, untreated, and histopathologically confirmed GB or BM were preoperatively examined with our physiological MRI approach as part of the cMRI protocol. RESULTS: Physiological MRI biomarker maps revealed several significant differences in the pathophysiology of GB and BM: Central necrosis was more hypoxic in GB than in BM (30 %; P = 0.036), which was associated with higher neovascularization activity (65 %; P = 0.043) and metabolic rate of oxygen (48 %; P = 0.004) in the adjacent contrast-enhancing viable tumor parts of GB. In peritumoral edema, GB infiltration caused neovascularization activity (93 %; P = 0.018) and higher microvascular perfusion (30 %; P = 0.022) associated with higher tissue oxygen tension (33 %; P = 0.020) and lower oxygen extraction from vasculature (32 %; P = 0.040). CONCLUSION: Our physiological MRI approach, which requires only 7 min of extra data acquisition time, might be helpful to noninvasively distinguish GB and BM based on pathophysiological differences. However, further studies including more patients are required.

The Diagnostic and Therapeutic Role of Leptin and Its Receptor ObR in Glioblastoma Multiforme.

Leptin has been recognized as a potential tumor growth promoter in various cancers including cranial tumor pathologies such as pituitary adenomas, meningiomas and gliomas. Despite recent advances in adjunctive therapy and the established surgical resection, chemo- and radiotherapy regimen, glioblastoma multiforme remains a particular diagnostic and therapeutic challenge among the intracranial tumor pathologies, with a poor long-term prognosis. Systemic inflammation and immune-metabolic signaling through diverse pathways are thought to impact the genesis and recurrence of brain tumors, and glioblastoma multiforme in particular. Among the various circulating mediators, leptin has gained especial diagnostic and therapeutic interest, although the precise relationship between leptin and glioblastoma biology remains largely unknown. In this narrative review (MEDLINE/OVID, SCOPUS, PubMed and manual searches of the bibliographies of known primary and review articles), we discuss the current literature using the following search terms: leptin, glioblastoma multiforme, carcinogenesis, immunometabolism, biomarkers, metformin, antidiabetic medication and metabolic disorders. An increasing body of experimental evidence implicates a relationship between the development and maintenance of gliomas (and brain tumors in general) with a dysregulated central and peripheral immune-metabolic network mediated by circulating adipokines, chemokines and cellular components, and in particular the leptin adipokine. In this review, we summarize the current evidence of the role of leptin in glioblastoma pathophysiology. In addition, we describe the status of alternative diagnostic tools and adjunctive therapeutics targeting leptin, leptin-receptors, antidiabetic drugs and associated pathways. Further experimental and clinical trials are needed to elucidate the mechanism of action and the value of immune-metabolism molecular phenotyping (central and peripheral) in order to develop novel adjunctive diagnostics and therapeutics for newly diagnosed and recurrent glioblastoma patients.

Skull Base Chordomas and Chondrosarcomas.

Skull base chordomas account for less than 0.2% and chondrosarcomas for less than 0.15% of all intracranial tumors. Although their clinical and imaging presentations are similar, they derive from different origins. Chordomas arise from embryonic remnants of the primitive notochord and chondrosarcomas from primitive mesenchymal cells or from the embryonic rest of the cranial cartilaginous matrix. Both entities are characterized by infiltration and destruction of the surrounding bone and soft tissue and a high locoregional recurrence rate. Chondrosarcomas, when treated with similar complex strategies, display a much better prognosis than chordomas. The overall survival is approximately 65% for chordomas and 80% for chondrosarcomas at 5 years and 30 and 50%, respectively, at 10 years. Chordomas are divided into the following 3 histological types: classical (conventional), chondroid, and dedifferentiated. Chondrosarcomas have conventional, mesenchymal, clear cell, and dedifferentiated subgroups. Both tumor entities often present with nonspecific symptoms, and headaches are the most reported initial symptom. Computed tomography and magnetic resonance imaging are required to determine the tumor localization and the extent of tumor growth. The treatment philosophy is to maximize tumor resection, minimize morbidity, and preserve function. Neurosurgical approaches commonly used for the resection of intracranial chordomas and chondrosarcomas are transsphenoidal, transbasal, cranio-orbitozygomatic, transzygomatic extended middle fossa, transcondylar, and transmaxillary approaches. Chordomas and chondrosarcomas are not sensitive to chemotherapy and there are no approved drugs for their treatment. The present treatment concept is a combination of surgical resection with a maximal excision and preserving patients' quality of life by adjuvant radiotherapy for both chordomas and chondrosarcomas.