Multi-center study finds postoperative residual non-enhancing component of glioblastoma as a new determinant of patient outcome.

INTRODUCTION: The aim of the present study is to assess whether postoperative residual non-enhancing volume (PRNV) is correlated and predictive of overall survival (OS) in glioblastoma (GBM) patients. METHODS: We retrospectively analyzed a total 134 GBM patients obtained from The University of Texas MD Anderson Cancer Center (training cohort, n = 97) and The Cancer Genome Atlas (validation cohort, n = 37). All patients had undergone postoperative magnetic resonance imaging immediately after surgery. We evaluated the survival outcomes with regard to PRNV. The role of possible prognostic factors that may affect survival after resection, including age, sex, preoperative Karnofsky performance status, postoperative nodular enhancement, surgically induced enhancement, and postoperative necrosis, was investigated using univariate and multivariate Cox proportional hazards regression analyses. Additionally, a recursive partitioning analysis (RPA) was used to identify prognostic groups. RESULTS: Our analyses revealed that a high PRNV (HR 1.051; p-corrected = 0.046) and old age (HR 1.031; p-corrected = 0.006) were independent predictors of overall survival. This trend was also observed in the validation cohort (higher PRNV: HR 1.127, p-corrected = 0.002; older age: HR 1.034, p-corrected = 0.022). RPA analysis identified two prognostic risk groups: low-risk group (PRNV < 70.2 cm3; n = 55) and high-risk group (PRNV ≥ 70.2 cm3; n = 42). GBM patients with low PRNV had a significant survival benefit (5.6 months; p = 0.0037). CONCLUSION: Our results demonstrate that high PRNV is associated with poor OS. Such results could be of great importance in a clinical setting, particularly in the postoperative management and monitoring of therapy.

Renal agenesis associated with contralateral ectopic ureter and hydroureteronephrosis.

Congenital anomalies of the kidney and the urinary tract such as renal agenesis and ectopic ureter have complex development. These anomalies have variable presentations and associations. In this report, we highlight the case of a young man with congenital renal agenesis presenting for a urinary tract infection. Abdominal and pelvic computed tomography imaging revealed the rare association of renal agenesis with contralateral ectopic ureter and subsequent hydroureteronephrosis. A urinary tract infection can be the presenting complication of such association, and a long follow-up is needed to anticipate the management.

Trans-urethral resection of bladder tumor (TURBT) and radiofrequency ablation of renal tumor: Rare etiologies of chyluria.

Chyluria is a rare entity which is caused by abnormal communication between the lymphatic system and the urinary tract, which allows the passage of chyle into the urine. Whenever symptomatic, chyluria presents with lower urinary tract symptoms such as dysuria and hematuria. Multiple imaging modalities can aid in diagnosis such as lymphoscintigraphy, retrograde pyelography, CT scan of the abdomen and pelvis, and magnetic resonance imaging. Numerous etiologies are associated with chyluria among which are surgical interventions. Partial and radical nephrectomy have been reported in a number of symptomatic and asymptomatic cases, while radiofrequency ablation of renal tumors has been very rarely reported. Herein, we report 2 cases of chyluria; one caused by trans-urethral resection of a bladder tumor and another by radiofrequency ablation of a renal oncocytoma. Fat-fluid level in the urinary bladder was seen on both precontrast and postcontrast images of CT scan of the abdomen and pelvis. Cystoscopy demonstrated no evidence of any abnormality of the urinary bladder.

Spontaneous rupture of the renal calyx secondary to a vesicoureteral junction calculus.

BACKGROUND: Spontaneous urinary collecting system rupture is caused by increased ureteral intraluminal pressure secondary to an obstruction. Rarely, a small stone exerts high intraureteral pressure especially if it is located distally. Many management modalities with good outcomes have been implicated. PURPOSE: Herein, we present a case of nontraumatic rupture of the renal calyx due to a 4 mm obstructing stone at the vesicoureteral junction. BASIC PROCEDURES: CT scan of abdomen and pelvis without contrast, CT scan of the abdomen and pelvis with intravenous contrast, Cystoscopy, Double-J ureter stent, Urinary Foley catheter. MAIN FINDINGS: The diagnosis was confirmed by CT imaging. Non-contrast enhanced CT scan of abdomen and pelvis showed obstructive calculi measuring 4 mm in the right vesicoureteral junction. Contrast-enhanced CT scan revealed leakage of contrast in the perinephric space at the right major calyx with intact bilateral ureters, suggestive of calyceal rupture. The treatment involved antibiotics and double-J stenting. PRINCIPAL CONCLUSIONS: This case demonstrates that spontaneous calyceal rupture should be suspected in urolothiasis patients presenting for a severe pain even if the calculus is small (less than 5 mm) and the laboratory markers are normal. An immediate management is required to relief symptoms and prevent further complications.

Incidentally discovered type 1 split cord malformation in an adult patient.

Split spinal cord syndrome (SCM), an entity of spinal dysraphisms, occurs rarely in adults and is associated with tethered cord syndrome, which commonly presents with back pain. Besides clinical findings, neuroimaging by Magnetic resonance imaging or computed tomography is needed for diagnosis. We report a case of a previously healthy 51-year-old man who presented for right upper abdominal quadrant pain. A computed tomography scan of the abdomen and pelvis incidentally discovered the diagnosis of type 1 SCM. This case highlights that SCM can remain asymptomatic throughout life to be diagnosed at one point by neuroimaging. Whenever no clinical complications exist, no surgical intervention might be indicated.

A Coclinical Radiogenomic Validation Study: Conserved Magnetic Resonance Radiomic Appearance of Periostin-Expressing Glioblastoma in Patients and Xenograft Models.

PURPOSE: Radiomics is the extraction of multidimensional imaging features, which when correlated with genomics, is termed radiogenomics. However, radiogenomic biological validation is not sufficiently described in the literature. We seek to establish causality between differential gene expression status and MRI-extracted radiomic-features in glioblastoma. EXPERIMENTAL DESIGN: Radiogenomic predictions and validation were done using the Cancer Genome Atlas and Repository of Molecular Brain Neoplasia Data glioblastoma patients (n = 93) and orthotopic xenografts (OX; n = 40). Tumor phenotypes were segmented, and radiomic-features extracted using the developed radiome-sequencing pipeline. Patients and animals were dichotomized on the basis of Periostin (POSTN) expression levels. RNA and protein levels confirmed RNAi-mediated POSTN knockdown in OX. Total RNA of tumor cells isolated from mouse brains (knockdown and control) was used for microarray-based expression profiling. Radiomic-features were utilized to predict POSTN expression status in patient, mouse, and interspecies. RESULTS: Our robust pipeline consists of segmentation, radiomic-feature extraction, feature normalization/selection, and predictive modeling. The combination of skull stripping, brain-tissue focused normalization, and patient-specific normalization are unique to this study, providing comparable cross-platform, cross-institution radiomic features. POSTN expression status was not associated with qualitative or volumetric MRI parameters. Radiomic features significantly predicted POSTN expression status in patients (AUC: 76.56%; sensitivity/specificity: 73.91/78.26%) and OX (AUC: 92.26%; sensitivity/specificity: 92.86%/91.67%). Furthermore, radiomic features in OX were significantly associated with patients with similar POSTN expression levels (AUC: 93.36%; sensitivity/specificity: 82.61%/95.74%; P = 02.021E-15). CONCLUSIONS: We determined causality between radiomic texture features and POSTN expression levels in a preclinical model with clinical validation. Our biologically validated radiomic pipeline also showed the potential application for human-mouse matched coclinical trials.

Learning MRI-based classification models for MGMT methylation status prediction in glioblastoma.

BACKGROUND AND OBJECTIVE: The O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation has been shown to be associated with improved outcomes in patients with glioblastoma (GBM) and may be a predictive marker of sensitivity to chemotherapy. However, determination of the MGMT promoter methylation status requires tissue obtained via surgical resection or biopsy. The aim of this study was to assess the ability of quantitative and qualitative imaging variables in predicting MGMT methylation status noninvasively. METHODS: A retrospective analysis of MR images from GBM patients was conducted. Multivariate prediction models were obtained by machine-learning methods and tested on data from The Cancer Genome Atlas (TCGA) database. RESULTS: The status of MGMT promoter methylation was predicted with an accuracy of up to 73.6%. Experimental analysis showed that the edema/necrosis volume ratio, tumor/necrosis volume ratio, edema volume, and tumor location and enhancement characteristics were the most significant variables in respect to the status of MGMT promoter methylation in GBM. CONCLUSIONS: The obtained results provide further evidence of an association between standard preoperative MRI variables and MGMT methylation status in GBM.

Radiomic Texture Analysis Mapping Predicts Areas of True Functional MRI Activity.

Individual analysis of functional Magnetic Resonance Imaging (fMRI) scans requires user-adjustment of the statistical threshold in order to maximize true functional activity and eliminate false positives. In this study, we propose a novel technique that uses radiomic texture analysis (TA) features associated with heterogeneity to predict areas of true functional activity. Scans of 15 right-handed healthy volunteers were analyzed using SPM8. The resulting functional maps were thresholded to optimize visualization of language areas, resulting in 116 regions of interests (ROIs). A board-certified neuroradiologist classified different ROIs into Expected (E) and Non-Expected (NE) based on their anatomical locations. TA was performed using the mean Echo-Planner Imaging (EPI) volume, and 20 rotation-invariant texture features were obtained for each ROI. Using forward stepwise logistic regression, we built a predictive model that discriminated between E and NE areas of functional activity, with a cross-validation AUC and success rate of 79.84% and 80.19% respectively (specificity/sensitivity of 78.34%/82.61%). This study found that radiomic TA of fMRI scans may allow for determination of areas of true functional activity, and thus eliminate clinician bias.

Glioblastoma-infiltrated innate immune cells resemble M0 macrophage phenotype.

Glioblastomas are highly infiltrated by diverse immune cells, including microglia, macrophages, and myeloid-derived suppressor cells (MDSCs). Understanding the mechanisms by which glioblastoma-associated myeloid cells (GAMs) undergo metamorphosis into tumor-supportive cells, characterizing the heterogeneity of immune cell phenotypes within glioblastoma subtypes, and discovering new targets can help the design of new efficient immunotherapies. In this study, we performed a comprehensive battery of immune phenotyping, whole-genome microarray analysis, and microRNA expression profiling of GAMs with matched blood monocytes, healthy donor monocytes, normal brain microglia, nonpolarized M0 macrophages, and polarized M1, M2a, M2c macrophages. Glioblastoma patients had an elevated number of monocytes relative to healthy donors. Among CD11b+ cells, microglia and MDSCs constituted a higher percentage of GAMs than did macrophages. GAM profiling using flow cytometry studies revealed a continuum between the M1- and M2-like phenotype. Contrary to current dogma, GAMs exhibited distinct immunological functions, with the former aligned close to nonpolarized M0 macrophages.

Multicenter imaging outcomes study of The Cancer Genome Atlas glioblastoma patient cohort: imaging predictors of overall and progression-free survival.

BACKGROUND: Despite an aggressive therapeutic approach, the prognosis for most patients with glioblastoma (GBM) remains poor. The aim of this study was to determine the significance of preoperative MRI variables, both quantitative and qualitative, with regard to overall and progression-free survival in GBM. METHODS: We retrospectively identified 94 untreated GBM patients from the Cancer Imaging Archive who had pretreatment MRI and corresponding patient outcomes and clinical information in The Cancer Genome Atlas. Qualitative imaging assessments were based on the Visually Accessible Rembrandt Images feature-set criteria. Volumetric parameters were obtained of the specific tumor components: contrast enhancement, necrosis, and edema/invasion. Cox regression was used to assess prognostic and survival significance of each image. RESULTS: Univariable Cox regression analysis demonstrated 10 imaging features and 2 clinical variables to be significantly associated with overall survival. Multivariable Cox regression analysis showed that tumor-enhancing volume (P = .03) and eloquent brain involvement (P < .001) were independent prognostic indicators of overall survival. In the multivariable Cox analysis of the volumetric features, the edema/invasion volume of more than 85 000 mm(3) and the proportion of enhancing tumor were significantly correlated with higher mortality (Ps = .004 and .003, respectively). CONCLUSIONS: Preoperative MRI parameters have a significant prognostic role in predicting survival in patients with GBM, thus making them useful for patient stratification and endpoint biomarkers in clinical trials.