Jason M. Hoover

Biopsy validation of 18F-DOPA PET and biodistribution in gliomas for neurosurgical planning and radiotherapy target delineation: results of a prospective pilot study

BACKGROUND Delineation of glioma extent for surgical or radiotherapy planning is routinely based on MRI. There is increasing awareness that contrast enhancement on T1-weighted images (T1-CE) may not reflect the entire extent of disease. The amino acid tracer (18)F-DOPA (3,4-dihydroxy-6-[18F] fluoro-l-phenylalanine) has a high tumor-to-background signal and high sensitivity for glioma imaging. This study compares (18)F-DOPA PET against conventional MRI for neurosurgical biopsy targeting, resection planning, and radiotherapy target volume delineation. METHODS Conventional MR and (18)F-DOPA PET/CT images were acquired in 10 patients with suspected malignant brain tumors. One to 3 biopsy locations per patient were chosen in regions of concordant and discordant (18)F-DOPA uptake and MR contrast enhancement. Histopathology was reviewed on 23 biopsies. (18)F-DOPA PET was quantified using standardized uptake values (SUV) and tumor-to-normal hemispheric tissue (T/N) ratios. RESULTS Pathologic review confirmed glioma in 22 of 23 biopsy specimens. Thirteen of 16 high-grade biopsy specimens were obtained from regions of elevated (18)F-DOPA uptake, while T1-CE was present in only 6 of those 16 samples. Optimal (18)F-DOPA PET thresholds corresponding to high-grade disease based on histopathology were calculated as T/N > 2.0. In every patient, (18)F-DOPA uptake regions with T/N > 2.0 extended beyond T1-CE up to a maximum of 3.5 cm. SUV was found to correlate with grade and cellularity. CONCLUSIONS (18)F-DOPA PET SUV(max) may more accurately identify regions of higher-grade/higher-density disease in patients with astrocytomas and will have utility in guiding stereotactic biopsy selection. Using SUV-based thresholds to define high-grade portions of disease may be valuable in delineating radiotherapy boost volumes.

The Effect of Deep-Tissue Massage Therapy on Blood Pressure and Heart Rate

AIM In the present study, we describe the effects of deep tissue massage on systolic, diastolic, and mean arterial blood pressure. MATERIALS AND METHODS The study involved 263 volunteers (12% males and 88% females), with an average age of 48.5. Overall muscle spasm/muscle strain was described as either moderate or severe for each patient. Baseline blood pressure and heart rate were measured via an automatic blood pressure cuff. Twenty-one (21) different soothing CDs played in the background as the deep tissue massage was performed over the course of the study. The massages were between 45 and 60 minutes in duration. The data were analyzed using analysis of variance with post-hoc Scheffes F-test. RESULTS Results of the present study demonstrated an average systolic pressure reduction of 10.4 mm Hg (p<0.06), a diastolic pressure reduction of 5.3 mm Hg (p<0.04), a mean arterial pressure reduction of 7.0 mm Hg (p<0.47), and an average heart rate reduction of 10.8 beats per minute (p<0.0003), respectively. CONCLUSIONS Additional scientific research in this area is warranted.

Use of preoperative magnetic resonance imaging T1 and T2 sequences to determine intraoperative meningioma consistency.

Background: Meningioma firmness is a critical factor that influences ease of resection and risk, notably when operating on tumors intimate with neurovascular structures such as the mesial sphenoid wing. This study develops a predictive tool using preoperative magnetic resonance imaging (MRI) characteristics to determine meningioma consistency. Methods: 101 patients with intracranial meningioma (50 soft/51 firm) were included. MRI characteristics of 38 tumors (19 soft/19 firm) were retrospectively reviewed to identify preoperative imaging features that were then correlated with intraoperative description of the tumor as either “soft and/or suckable” or “firm and/or fibrous”. Criteria were developed to predict consistency and then blindly applied to the remaining 63 meningiomas (31 soft/32 firm). Results: The overall sensitivities for detecting soft and firm consistency were 90% and 56%, respectively (95% CI = 73–97% and 38–73%; P < 0.001). Compared to gray matter, meningiomas that were T2 hypointense were almost always firm. Soft meningiomas were hyperintense on T2 and hypointense on T1. Soft meningiomas were slightly larger and less likely to be associated with edema. There was a slight preponderance of firm meningiomas in the infratentorial compartment. Grade of meningioma was not predictive. Contrast enhancement, diffusion restriction, changes in overlying bone, intratumoral cysts, and angiographic features were not predictable. Conclusions: This tool using T1 and T2 series predicts meningioma consistency. Such knowledge should assist the surgeon in preoperative planning and counseling.

Surgical outcomes in recurrent glioma.

OBJECT The object of this study was to assess outcomes after surgery for recurrent intracranial glioma. METHODS The authors retrospectively reviewed cases involving adult patients with intracranial glioma patients undergoing initial surgery (biopsy or resection) and one or more additional surgeries at their institution. RESULTS A total of 323 operations were performed in 131 patients. The median survival was 76 months after first surgery, 36 months after second, 24 months after third, and 26.5 months after 4 or more surgeries. The overall complication rate was 12.8% after first surgery, 27.0% after second (OR 2.52, p = 0.0068), 22.0% after third (OR 1.92, not statistically significant [NS]), and 22.2% after 4 or more (OR 1.95, NS). Neurological complications occurred in 4.8% of patients at first surgery, 12.1% at second (OR 2.7, p = 0.0437), 8.2% at third (OR 1.75, NS), and 11.1% at 4 or more surgeries (OR 2.4583, NS). Regional complications occurred in 6.2% after first surgery, 9.9% after second surgery (OR 2.30, p = 0.095), 13.7% after third surgery (OR 3.31, p = 0.015), and 22.2% after 4 or more surgeries (OR 5.95, p = 0.056). Systemic complications occurred in 3.2% after first surgery, in 7.3% after second surgery (OR 2.3, p = 0.NS), in 4.1% after third surgery (OR 1.3, NS), and 0% after 4 or more surgeries. Reduction in Karnofsky Performance Status score occurred in 0% after first surgery, 8.1% after second surgery (OR 3.13, p = 0.0018), 10.2% after third surgery (OR 5.52, p < 0.0001), and 11.1% after 4 or more surgeries (OR 1.037, NS). CONCLUSIONS Postoperative survival is relatively prolonged but complication risk increases in patients with glioma who undergo multiple cranial surgeries. The largest increase in neurological risk occurs between the first and second surgery. In contrast, regional complication risk increases consistently with each surgery. The risk of systemic complications is not significantly altered with increasing surgeries. However, these complications only result in a modestly increased risk of functional decline after 2 or more surgeries. These findings may help counsel patients considering multiple glioma surgeries.

An analysis of remifentanil in the pulmonary vascular bed of the cat

In this investigation we sought to identify the role of remifentanil in the feline pulmonary vascular bed. Using adult mongrel cats in separate experiments, the effects of glibenclamide (adenosine triphosphate-sensitive K+ channel blocker), diphenhydramine (histamine H1-receptor antagonist), L-N5-(1-Iminoethyl) ornithine hydrochloride (nitric oxide synthase inhibitor), and naloxone (opioid receptor antagonist) were investigated in pulmonary arterial responses to remifentanil (opioid agonist), pinacidil (adenosine triphosphate-sensitive K+ channel activator), and bradykinin (nitric oxide synthase inducer). Under increased tone conditions in the isolated left lower lobe vascular bed of the cat, remifentanil induced a dose-dependent vasodepressor response that was not significantly altered after administration of glibenclamide and L-N5-(1-Iminoethyl) ornithine hydrochloride. Responses to remifentanil were significantly attenuated after administration of diphenhydramine and naloxone. The results suggest that remifentanil has potent vasodepressor activity in the feline pulmonary vascular bed and that these responses are mediated by histamine and opioid receptor sensitive pathways.

Morphine, opioids, and the feline pulmonary vascular bed

Background: Opioid‐induced vasodepressor responses have been reported in a variety of species and laboratory models. The aim of this study was to ascertain the relative potencies of different clinically relevant opioids compared with traditional vasodepressor agents in the feline pulmonary vascular bed. A second aim was to study the effects of morphine and to identify the receptors involved in the mediation or the modulation of these effects.

Analysis of the effects of fentanyl in the feline pulmonary vascular bed

The objective of this study was to test the hypothesis that fentanyl induces a depressor response in the pulmonary vascular bed of the cat and to identify the receptors involved in the mediation or modulation of these effects. The authors conducted a prospective vehicle-controlled study at a university research laboratory using intact chest preparation in adult mongrel cats. In separate experiments, the effects of diphenhydramine (histamine receptor blocker), glibenclamide (ATP-sensitive K+ channel blocker), l-N5-(1-Iminoethyl) ornithine hydrochloride (l-NIO) (nitric oxide synthase inhibitor), nimesulide (selective cyclooxygenase [COX]-2 inhibitor), and naloxone (opiate receptor antagonist) were investigated on pulmonary arterial responses to fentanyl and other agonists in the pulmonary vascular bed of the cat. The systemic pressure and lobar arterial perfusion pressure were continuously monitored, electronically averaged, and recorded. In the feline pulmonary vascular bed of the isolated left lower lobe, fentanyl induced a dose-dependent vasodepressor response that was not significantly altered after administration of glibenclamide, l-NIO, and nimesulide. However, the responses to fentanyl were significantly attenuated after administration of diphenhydramine and naloxone. The results of the present study suggest that fentanyl has potent vasodepressor activity in the pulmonary vascular bed of the cat and that this response may be mediated or modulated by both histaminergic and opiate receptor sensitive pathways.

Intramedullary melanotic schwannoma.

We present a case of an intramedullary melanotic schwannoma (IMS) of the thoracic spinal cord. To our knowledge, this is the seventh reported case of an IMS of the central nervous system. Schwannomas are benign nerve sheath tumors of neural crest origin composed entirely of well differentiated Schwann cells that typically occur in peripheral nerves. Both the intramedullary location and the melanotic component of the reported lesion make it exceedingly rare. We will present our case, theories as to the origin of these tumors, clues in radiographic identification, and current clinical follow-up recommendations.

Use of Preoperative MRI to Predict Vestibular Schwannoma Intraoperative Consistency and Facial Nerve Outcome

Objectives We sought to identify if preoperative schwannoma magnetic resonance imaging (MRI) intensities might predict intraoperative consistency. We then determined whether consistency correlated with facial nerve outcomes. Design Operative reports from 2000 to 2010 were searched for tumor description as either soft and/or suckable or firm and/or fibrous. Preoperative T1 and T2 sequences were then reviewed to identify intensities relative to gray matter. Facial nerve function was recorded at the time of most recent follow-up. Results Forty-six patients were included. No tumors were T1 hyperintense. Soft and firm schwannomas were equally likely to be T1 hypointense. On T2 sequences, however, soft schwannomas were more likely to be hyperintense (88% versus 14%, p < 0.005) whereas firm schwannomas were more likely to be hypointense (86% versus 6%, p < 0.005). There was a tendency for firm schwannomas to have worse facial nerve outcomes (43% versus 19%, p = 0.14). Conclusions Prediction of vestibular schwannoma intraoperative consistency based on T2 intensity seems promising. Furthermore, though not statistically significant, in this small pilot study firm schwannomas tended to have worse facial nerve outcomes. This potential ability to predict consistency and its correlation with facial nerve outcome may assist the surgeon in preoperative planning and patient counseling, though further data needs to be accumulated.

Clinical Trials in Brain Tumor Surgery

The prognosis for patients diagnosed with primary central nervous system tumors, such as gliomas, remains generally poor. Improved treatment (standard therapies and novel strategies) is needed. Glioma surgery is a key part of standard treatment and has established roles in providing tissue for diagnosis and in tumor debulking. Several techniques to increase safe surgical resection have been investigated. In addition, novel surgical modalities introducing therapeutic agents locally are increasingly common. This article reviews recent glioma surgery clinical trials, focusing on outcome studies, novel surgical techniques, and local therapeutic agent delivery.