Markus M. Luedi

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.

139 Clinically Applicable and Biologically Validated MRI Radiomic Test Method Predicts Glioblastoma Genomic Landscape and Survival.

INTRODUCTION Imaging is the modality of choice for noninvasive characterization of biological tissue and organ systems; imaging serves as early diagnostic tool for most disease processes and is rapidly evolving, thus transforming the way we diagnose and follow patients over time. A vast number of cancer imaging characteristics have been correlated to underlying genomics; however, none have established causality. Therefore, our objectives were to test if there is a causal relationship between imaging and genomic information; and to develop a clinically relevant radiomic pipeline for glioblastoma molecular characterization. METHODS Functional validation was performed using a prototypic in vivo RNA-interference-based orthotopic xenograft mouse model. The automated pipeline collects 4800 MRI-derived texture features per tumor. Using univariate feature selection and boosted tree predictive modeling, a patient-specific genomic probability map was derived and patient survival predicted (The Cancer Genome Atlas/MD Anderson data sets). RESULTS Data demonstrated a significant xenograft to human association (area under the curve [AUC] 84%, P < .001). Further, epidermal growth factor receptor amplification (AUC 86%, P < .0001), O-methylguanine-DNA-methyltransferase methylation/expression (AUC 92%, P = .001), glioblastoma molecular subgroups (AUC 88%, P = .001), and survival in 2 independent data sets (AUC 90%, P < .001) was predicted. CONCLUSION Our results for the first time illustrate a causal relationship between imaging features and genomic tumor composition. We present a directly clinically applicable analytical imaging method termed Radiome Sequencing to allow for automated image analysis, prediction of key genomic events, and survival. This method is scalable and applicable to any type of medical imaging. Further, it allows for human-mouse matched coclinical trials, in-depth end point analysis, and upfront noninvasive high-resolution radiomics-based diagnostic, prognostic, and predictive biomarker development.

Retained transorbital foreign body with intracranial extension after pipe bomb explosion.

Background Penetrating brain injuries caused by explosions are survived in extremely rare cases only. However, potential casualties of such cases may be encountered by regular physicians even outside a war zone, e.g., due to an assault or terror blast. There is very limited literature to this end; therefore, we report the successful neurosurgical management of a penetrating head injury due to a pipe bomb explosion. Case Description A 19-year-old man was brought to the ER with a swollen, bleeding right orbit, and a severely injured left hand after having sustained an unwitnessed explosion from a self-made pipe bomb. He presented with a GCS (Glasgow Coma Scale) of 15 at time of admission, work-up revealed an intracranial retained metal fragment measuring 5 × 1 × 0.2 cm lodged retro-orbitally and in the skull base. The patient underwent emergent right temporal craniotomy and temporal lobectomy and simultaneous right enucleation before the petrous bone and sphenoid wing lodged metal fragment was successfully removed. Conclusion This case underscores the importance of having a high suspicion for the presence of an intracranial injury and a retained foreign body in the setting of a penetrating head injury. Aggressive and timely workup as well as expeditious surgical management are crucial in these settings and can generate exceptionally good outcomes despite a major trauma.

A dexamethasone-regulated gene signature is prognostic for poor survival in glioblastoma patients

Background: Dexamethasone is reported to induce both tumor-suppressive and tumor-promoting effects. The purpose of this study was to identify the genomic impact of dexamethasone in glioblastoma stem cell (GSC) lines and its prognostic value; furthermore, to identify drugs that can counter these side effects of dexamethasone exposure. Methods: We utilized 3 independent GSC lines with tumorigenic potential for this study. Whole-genome expression profiling and pathway analyses were done with dexamethasone-exposed and control cells. GSCs were also co-exposed to dexamethasone and temozolomide. Risk scores were calculated for most affected genes, and their associations with survival in The Cancer Genome Atlas and Repository of Molecular Brain Neoplasia Data databases. In silico Connectivity Map analysis identified camptothecin as antagonist to dexamethasone-induced negative effects. Results: Pathway analyses predicted an activation of dexamethasone network (z-score: 2.908). Top activated canonical pathways included “role of breast cancer 1 in DNA damage response” (P=1.07E–04). GSCs were protected against temozolomide-induced apoptosis when coincubated with dexamethasone. Altered cellular functions included cell movement, cell survival, and apoptosis with z-scores of 2.815, 5.137, and –3.122, respectively. CCAAT/enhancer binding protein beta (CEBPB) was activated in a dose dependent manner specifically in slow-dividing “stem-like” cells. CEBPB was activated in dexamethasone-treated orthotopic tumors. Patients with high risk scores had significantly shorter survival. Camptothecin was validated as potential partial neutralizer of dexamethasone-induced oncogenic effects. Conclusions: Dexamethasone exposure induces a genetic program and CEBPB expression in GSCs that adversely affects key cellular functions and response to therapeutics. High risk scores associated with these genes have negative prognostic value in patients. Our findings further suggest camptothecin as a potential neutralizer of adverse dexamethasone-mediated effects.

Primary epidural lymphocyte-depleted Hodgkin’s lymphoma of the thoracic spine – presentation of a rare disease variant

BackgroundLymphocyte-depleted Hodgkin’s lymphoma is the rarest form of classical Hodgkin’s lymphoma, accounting for < 1% of all cases. Patients often have advanced-stage disease at the time of presentation with an aggressive clinical course. Even more uncommon is primary extranodal disease and rarely it will be presenting with spinal cord compression.Case presentationAn 88-year-old Caucasian female presented with a history of upper back pain for several months and new onset bilateral leg numbness and weakness. MRI of the spine showed a dorsal epidural lesion with cord compression at T1-T4 with involvement of the paraspinal muscles. The patient received urgent surgical decompression, with final histopathology showing a lymphocyte-depleted Hodgkin’s lymphoma. Systemic work-up did not show evidence of nodal disease. Following surgery, she received a course of radiotherapy with good outcome.ConclusionTo the best of our knowledge, this is the first reported case of primary lymphocyte-depleted Hodgkin lymphoma presenting as epidural spinal cord compression. Our report, in conjunction with a review of the literature, suggests that surgical intervention is clearly indicated in de novo disease followed by radiotherapy.

Implications of Perioperative Team Setups for Operating Room Management Decisions.

BACKGROUND: Team performance has been studied extensively in the perioperative setting, but the managerial impact of interprofessional team performance remains unclear. We hypothesized that the interplay between anesthesiologists and surgeons would affect operating room turnaround times, and teams that worked together over time would become more efficient. METHODS: We analyzed 13,632 surgical cases at our hospital that involved 64 surgeons and 48 anesthesiologists. We detrended and adjusted the data for potential confounders including age, American Society of Anesthesiologists physical status, and surgical list (scheduled cases of specific surgical specialties). The surgical lists were categorized as ear, nose, and throat surgery; trauma surgery; general surgery; and gynecology. We assessed the relationship between turnaround times and assignment of different anesthesiologists to specific surgeons using a Monte Carlo simulation. RESULTS: We found significant differences in team performances among the different surgical lists but no team learning. We constructed managerial decision tables for the assignment of anesthesiologists to specific surgeons at our hospital. We defined a decision algorithm based on these tables. Our analysis indicated that had this algorithm been used in staffing the operating room for the surgical cases represented in our data, median turnaround times would have a reduction potential of 6.8% (95% confidence interval 6.3% to 7.1%). CONCLUSIONS: A surgeon is usually predefined for scheduled surgeries (surgical list). Allocation of the right anesthesiologist to a list and to a surgeon can affect the team performance; thus, this assignment has managerial implications regarding the operating room efficiency affecting turnaround times and thus potentially overutilized time of a list at our hospital.

Gunshot Injuries to the Head

Traumatic brain injury (TBI) remains a major cause of death and disability worldwide, and missile-induced TBI remains the most deadly of all traumas since first reported and has always been associated with high mortality and morbidity. The prevalence of TBI secondary to gunshots is strikingly variable and reflects the global scenery of violence. Injuries from gunshot wounds (GSW) to the head place an extreme economic burden on the public while disabling the victims in the zenith of their life and imposing enormous medical, legal, and emotional costs. Since every gun/projectile combination is associated with a typical pattern of injury, war injuries differ significantly from others. We will focus here on predominantly penetrating civilian gunshot wounds with low muzzle velocity (<1,000 f/s) as they occur in the setting of homicide and suicide attempts or during accidents. Many surgeons did take patients to the OR over the last 30 years, and they have achieved a remarkable reduction in morbidity from well above 50 % to less than 25 % in patients admitted with severe brain injury. However, in the setting of increasingly limited resources, recent research focus has shifted toward more precise prediction of survival as well as on better functional outcome.

Interdisciplinary Dialogue Is Needed When Defining Perioperative Recommendations: Conflicting Guidelines for Anesthetizing Patients for Pilonidal Surgery.

National or international guidelines can help surgeons and anesthesiologists make treatment decisions, but the existence of conflicting recommendations can hinder treatment rather than helping. A case in point is the treatment of pilonidal sinus disease, a chronic subcutaneous infection located in the sacrococcygeal area. Its incidence is rising, reaching almost 100/100,000 inhabitants. Three surgical societies have proposed guidelines for treating the disease, but these guidelines vary greatly in their approach to anesthesia. Who should provide input into guidelines? And how can medical disciplines successfully collaborate? Anesthesiologists must be involved in defining perioperative recommendations not only in patients with pilonidal sinus disease.

Laser may reduce recurrence rate in pilonidal sinus disease by reducing captured occipital hair

Dear editor, Just recently, the interesting article of Khan et al. on Bcontrol of hair growth using long-pulsed alexandrite laser^ has been published [1]. Describing results from laser treatment of nonhealing wounds following recurrent pilonidal sinus disease (PSD) surgery, cost effectiveness, and disease-free time are compiled. Hair density measurements before and after laser therapy are given, which is quite an arduous task to compile. The author can be congratulated for their efforts. However, minor issues need to be addressed.

Corrigendum to “Automated Feature Extraction in Brain Tumor by Magnetic Resonance Imaging Using Gaussian Mixture Models”

[This corrects the article DOI: 10.1155/2015/868031.].