The safety and efficacy of the Stryker OptaBlate™ Bone Tumor Ablation system for vertebral body metastases.

Background: Metastatic spinal lesions are a significant cause of morbidity and decreased quality of life in those with a high tumor burden. Despite treatment modalities such as medical therapy (e.g., chemotherapy, steroids), spinal augmentation procedures, and radiation therapy, many patients still experience refractory back pain due to neoplastic infiltration of the vertebral body and/or pathologic compression fractures. With the aim to address refractory pain in patients who have exhausted conventional treatment options, Stryker developed the OptablateTM Bone Tumor Ablation system (BTA; Stryker Corporation, Kalamazoo, MI), which delivers radiofrequency energy to pathologic vertebral body lesions. In this preliminary single-institution study, we characterize the use of the BTA system in 11 patients undergoing kyphoplasty for pathologic spinal lesions with the goal to demonstrate the impact of this novel technology on refractory pain in this challenging clinical setting. Methods: A single-center retrospective chart review was performed on all patients identified as those receiving tumor ablation/kyphoplasty for spinal neoplasms using the OptablateTM BTA system performed by a single surgeon at the University of Oklahoma Medical Center. Sex, age, primary lesion type, presenting symptomatology, spinal level, time of follow-up, and outcome were obtained from the electronic medical record (EMR). Results: Eleven patients (4 males, 7 females) with a mean age of 62 (range, 38-82) years had an average follow-up time of 6 months. Presenting symptoms attributed to spinal pathology included back pain (n = 11, 100%), pathologic fracture (n = 6, 55%), and lower extremity weakness (n = 3, 27%). A total of 20 lesions were ablated at 12 vertebral levels. Eight patients (73%) had improved pain. No complications were reported. Conclusion: This preliminary study documents the safety of the BTA system, in addition to its diverse use across many levels. The majority of patients reported improvement in their pain. Further study is required to fully characterize the use of the BTA system in those with neoplastic spinal pathology.

Boomer Sooner: neurosurgery at the University of Oklahoma.

Neurosurgery at the University of Oklahoma has played a pivotal role in the development of the specialty in the state. Its history spans nearly 90 years, beginning in 1931 when Dr. Harry Wilkins established the first neurosurgical practice in the state at the University of Oklahoma. Together with his first trainee, Dr. Jess Herrmann, Wilkins established the Division of Neurosurgery and its training program in 1946. Through their tireless work, the division and its residency program gained renown for its patient care and teaching, and this tradition was carried forward by its subsequent leaders. The Department of Neurosurgery was established in 1993. From humble beginnings, neurosurgery at the University of Oklahoma has grown a comprehensive residency program with an intensive curriculum, leveraging the clinical and academic breadth afforded by relationships with the College of Medicine, the University of Oklahoma Health Sciences Center, and allied clinical and research partners. Here, the authors recount the history of neurosurgery at the University of Oklahoma, the flagship academic neurosurgical program in the state.

[18F]fluorothymidine PET imaging in the diagnosis of leptomeningeal involvement with diffuse large B-cell lymphoma.

The diagnosis of leptomeningeal carcinomatosis remains difficult despite improvement in central nervous system (CNS) imaging and cytologic examination of the cerebral spinal fluid. False-negative results are common, providing obstacles in assessing both prophylactic and therapeutic efforts. As a result of increased survival of patients with a variety of systemic neoplasms it is likely that central nervous involvement will need to be addressed more often. This article presents a patient with a diffuse large B-cell lymphoma with polymorphic features. Imaging using 18F-labeled fluorodeoxythymidine (FLT) proved useful in demonstrating both parenchymal and leptomeningeal CNS involvement. The potential for FLT to identify proliferative tissue may make it uniquely suitable for detection of CNS malignant disease.

Differential expression of type 2 3α/type 5 17ß-hydroxysteroid dehydrogenase (AKR1C3) in tumors of the central nervous system.

Human aldo-keto reductase (AKR) 1C3, type 2 3α-hydroxysteroid dehydrogenase (HSC)/ type 5 17ß-HSD, is known to be involved in steroids, prostaglandins, and lipid aldehydes metabolism. The expression of AKR1C3 has been demonstrated in hormone-dependent normal tissues such as breast, endometrium, prostate, and testis; and de -regulated AKR1C3 expression has been shown in breast carcinoma, endometrial hyperplasia, endometrial carcinoma, and prostate carcinoma. AKR1C3 expression has also been demonstrated in hormone-independent normal tissues (renal tubules and urothelium) and neoplastic tissues (renal cell carcinoma, Wilm's tumor, and urothelial cell carcinoma). Extensive expression of AKR1C3 in normal and neoplastic as well as hormone-dependent and hormone-independent tissues indicates that AKR1C3 may have functions beyond steroid hormone metabolism. In this report, we describe a widespread expression of AKR1C3 in glial neoplasms and meningiomas, with limited expression in medulloblastoma and no expression in Schwannoma. These tumors, except meningioma, are not classically considered to be sex hormone-dependent or related brain tumors. The current results corroborate our earlier observations that AKR1C3 is expressed in both sex hormone-dependent and hormone-independent malignancies. Similar to AKR1C3 distribution in Wilm's tumor, we also demonstrate that expression of AKR1C3 is reduced in tumors with embryonic phenotypes.

FOXG1 dysregulation is a frequent event in medulloblastoma.

Medulloblastomas represent 20% of malignant brain tumors of childhood. Although, they show multiple, non-random genomic alterations, no common, early genetic event involving all histologic types of medulloblastomas have been described. Nineteen medulloblastomas were analyzed using chromosomal comparative genomic hybridization (cCGH). Nine tumors with the most frequent number of genetic changes were further analyzed using bacterial artificial chromosome array CGH (aCGH). With aCGH, the frequency of gains and losses were higher than with cCGH. Chromosome 2p gains spanning 2p11-2p25 including N-myc locus, 2p24.1 were detected in 5/9 (55%) tumors while 14q12 gains were detected in 6/9 (67%) tumors. The 14q12 locus overlapped with the FOXGI gene locus. Quantitative real time PCR showed a 2-7-fold copy gain for FOXG1 in all the nine tumors. Protein expression was demonstrated by immunohistochemistry in all histologic types. The expression of FOXG1 and p21cip1 showed an inverse relationship. FOXG1 copy gain (>2 to 21 folds) was seen in 93% (55/59) of a validating set of tumors and showed a positive correlation with protein expression (Spearman's rank order correlation coefficient = 0.276; P = 0.038) representing the first report of FOXG1 dysregulation in medulloblastoma. Modulation of FOXG1 expression in DAOY cell line using siRNA showed a modest decrease in proliferation with a 2-fold upregulation of p21cip1. Current reports indicate that FOXG1 represses TGF-beta induced expression of p21cip1 and cytostasis, and forms a transcriptional repressor complex with Notch signaling induced hes1. Our findings are consistent with a role for FOXG1 in the inhibition of TGF-beta induced cytostasis in medulloblastoma.