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Sujit S. Prabhu and Franco DeMonte

The authors describe a case of a complex glomus jugulare tumor with extensive involvement of the venous system. The entire left internal jugular vein up to its innominate insertion was involved with tumor, with proximal extension to the sigmoid sinus, transverse sinus, and the torcular herophili. Gross-total resection of the tumor required a two-stage median sternotomy. This is the first case report of a glomus jugulare tumor in which there was such extensive involvement of the venous system, requiring a multidisciplinary team approach for complete resection.

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Jonathan G. Thomas, Ganesh Rao, Yvonne Kew and Sujit S. Prabhu

OBJECTIVE

Glioblastoma (GBM) is the most common and deadly malignant primary brain tumor. Better surgical therapies are needed for newly diagnosed GBMs that are difficult to resect and for GBMs that recur despite standard therapies. The authors reviewed their institutional experience of using laser interstitial thermal therapy (LITT) for the treatment of newly diagnosed or recurrent GBMs.

METHODS

This study reports on the pre-LITT characteristics and post-LITT outcomes of 8 patients with newly diagnosed GBMs and 13 patients with recurrent GBM who underwent LITT.

RESULTS

Compared with the group with recurrent GBMs, the patients with newly diagnosed GBMs who underwent LITT tended to be older (60.8 vs 48.9 years), harbored larger tumors (22.4 vs 14.6 cm3), and a greater proportion had IDH wild-type GBMs. In the newly diagnosed GBM group, the median progression-free survival and the median survival after the procedure were 2 months and 8 months, respectively, and no patient demonstrated radiographic shrinkage of the tumor on follow-up imaging. In the 13 patients with recurrent GBM, 5 demonstrated a response to LITT, with radiographic shrinkage of the tumor following ablation. The median progression-free survival was 5 months, and the median survival was greater than 7 months.

CONCLUSIONS

In carefully selected patients with recurrent GBM, LITT may be an effective alternative to surgery as a salvage treatment. Its role in the treatment of newly diagnosed unresectable GBMs is not established yet and requires further study.

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Marcos V. C. Maldaun, Dima Suki, Frederick F. Lang, Sujit Prabhu, Weiming Shi, Gregory N. Fuller, David M. Wildrick and Raymond Sawaya

Object. The goal of this study was to determine whether the presence of a large tumor cyst was associated with improved outcome in patients undergoing surgery for newly diagnosed glioblastomas multiforme (GBMs) by comparing these patients with a matched cohort of patients with noncystic GBMs in clinical features, tumor imaging characteristics, survival, and time to tumor recurrence after surgery.

Methods. A retrospective analysis was conducted in 22 patients by using imaging information and chart reviews of operative reports of GBMs with large cysts (≥ 50% of tumor volume) at The University of Texas M. D. Anderson Cancer Center between 1993 and 2002. Clinical and neurosurgical outcomes and recurrence rates were studied. A statistical comparison was made with a matching cohort of 22 patients with noncystic GBMs.

No significant differences in clinical variables were found between the cohort with cystic GBMs and the matched cohort with noncystic GBMs. To avoid bias in preoperative assessment of tumor volume, the tumor burden was compared in patients whose tumors had cysts (excluding the cystic mass) and in patients whose tumors did not contain cysts. There was no statistically significant difference between the two groups (p = 0.8). In patients with cystic GBMs the median survival time after surgery was 18.2 months (95% confidence interval [CI] 11.9–24.5 months) and at 2 years 43% of the patients were still alive. In comparison, in patients with noncystic GBMs, the median survival time was 14.3 months (95% CI 12.1–16.4 months) and only 16% of patients were alive at 2 years. The median time to tumor recurrence was 7.6 months (95% CI 0.01–18 months) in patients harboring cystic GBMs and 4.2 months (95% CI 1.8–6.6 months) in the matched cohort (log-rank test, p = 0.04). In the cystic GBM group, no recurrence was observed in 53% of patients at 6 months, 45% at 1 year, and 38% at 2 years after surgery, whereas the corresponding numbers for the noncystic group were 36, 14, and 9%, respectively.

Conclusions. The results indicate that patients harboring a GBM that contains a large cyst survive longer and have a longer time to recurrence than those who lack such a cyst. This is the first such observation in the literature.

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Rewati Raman Sharma, Harshad C. Parekh, Sujit Prabhu, Nihal T. Gurusinghe and George Bertolis

✓ The authors report a symptomatic congenitally anomalous ectatic vertebral artery not passing through the transverse foramen of the atlas (C-1), but instead piercing the dura mater below the posterior arch of the C-1 in the atlantoaxial (C1–2) interlaminar space. This occurrence is exceptionally rare, but in this case it was uniquely associated with occipital neuralgia due to vascular compression of the C-2 root. Microvascular decompression was curative. Neuroradiological and surgical findings are presented and their implications discussed.

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Sujit S. Prabhu, Jaime Gasco, Sudhakar Tummala, Jefrey S. Weinberg and Ganesh Rao

Object

The object of this study was to describe the utility and safety of using a single probe for combined intraoperative navigation and subcortical mapping in an intraoperative MR (iMR) imaging environment during brain tumor resection.

Methods

The authors retrospectively reviewed those patients who underwent resection in the iMR imaging environment, as well as functional electrophysiological monitoring with continuous motor evoked potential (MEP) and direct subcortical mapping combined with diffusion tensor imaging tractography.

Results

As a navigational tool the monopolar probe used was safe and accurate. Positive subcortical fiber MEPs were obtained in 10 (83%) of the 12 cases. In 10 patients in whom subcortical MEPs were recorded, the mean stimulus intensity was 10.4 ± 5.2 mA and the mean distance from the probe tip to the corticospinal tract (CST) was 7.4 ± 4.5 mm. There was a trend toward worsening neurological deficits if the distance to the CST was short, and a small minimum stimulation threshold was recorded indicating close proximity of the CST to the resection margins. Gross-total resection (95%–100% tumor removal) was achieved in 11 cases (92%), whereas 1 patient (8%) had at least a 90% tumor resection. At the end of 3 months, 2 patients (17%) had persistent neurological deficits.

Conclusions

The monopolar probe can be safely implemented in an iMR imaging environment both for navigation and stimulation purposes during the resection of intrinsic brain tumors. In this study there was a trend toward worsening neurological deficits if the distance from the probe to the CST was short (< 5 mm) indicating close proximity of the resection cavity to the CST. This technology can be used in the iMR imaging environment as a surgical adjunct to minimize adverse neurological outcomes.

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Zhi-Jian Chen, George T. Gillies, William C. Broaddus, Sujit S. Prabhu, Helen Fillmore, Ryan M. Mitchell, Frank D. Corwin and Panos P. Fatouros

Object. The goal of this study was to validate a simple, inexpensive, and robust model system to be used as an in vitro surrogate for in vivo brain tissues in preclinical and exploratory studies of infusion-based intraparenchymal drug and cell delivery.

Methods. Agarose gels of varying concentrations and porcine brain were tested to determine the infusion characteristics of several different catheters at flow rates of 0.5 and 1 µl per minute by using bromophenol blue (BPB) dye (molecular weight [MW] ∼690) and gadodiamide (MW ∼573). Magnetic resonance (MR) imaging and videomicroscopy were used to measure the distribution of these infusates, with a simultaneous measurement of infusion pressures. In addition, the forces of catheter penetration and movement through gel and brain were measured.

Agarose gel at a 0.6% concentration closely resembles in vivo brain with respect to several critical physical characteristics. The ratio of distribution volume to infusion volume of agarose was 10 compared with 7.1 for brain. The infusion pressure of the gel demonstrated profiles similar in configuration and magnitude to those of the brain (plateau pressures 10–20 mm Hg). Gadodiamide infusion in agarose closely resembled that in the brain, as documented using T1-weighted MR imaging. Gadodiamide distribution in agarose gel was virtually identical to that of BPB dye, as documented by MR imaging and videomicroscopy. The force profile for insertion of a silastic catheter into agarose gel was similar in magnitude and configuration to the force profile for insertion into the brain. Careful insertion of the cannula using a stereotactic guide is critical to minimize irregularity and backflow of infusate distribution.

Conclusions. Agarose gel (0.6%) is a useful surrogate for in vivo brain in exploratory studies of convection-enhanced delivery.

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Adam S. Wu, Victoria T. Trinh, Dima Suki, Susan Graham, Arthur Forman, Jeffrey S. Weinberg, Ian E. McCutcheon, Sujit S. Prabhu, Amy B. Heimberger, Raymond Sawaya, Xuemei Wang, Wei Qiao, Kenneth R. Hess and Frederick F. Lang

Object

Seizures are a potentially devastating complication of resection of brain tumors. Consequently, many neurosurgeons administer prophylactic antiepileptic drugs (AEDs) in the perioperative period. However, it is currently unclear whether perioperative AEDs should be routinely administered to patients with brain tumors who have never had a seizure. Therefore, the authors conducted a prospective, randomized trial examining the use of phenytoin for postoperative seizure prophylaxis in patients undergoing resection for supratentorial brain metastases or gliomas.

Methods

Patients with brain tumors (metastases or gliomas) who did not have seizures and who were undergoing craniotomy for tumor resection were randomized to receive either phenytoin for 7 days after tumor resection (prophylaxis group) or no seizure prophylaxis (observation group). Phenytoin levels were monitored daily. Primary outcomes were seizures and adverse events. Using an estimated seizure incidence of 30% in the observation arm and 10% in the prophylaxis arm, a Type I error of 0.05 and a Type II error of 0.20, a target accrual of 142 patients (71 per arm) was planned.

Results

The trial was closed before completion of accrual because Bayesian predictive probability analyses performed by an independent data monitoring committee indicated a probability of 0.003 that at the end of the study prophylaxis would prove superior to observation and a probability of 0.997 that there would be insufficient evidence at the end of the trial to choose either arm as superior. At the time of trial closure, 123 patients (77 metastases and 46 gliomas) were randomized, with 62 receiving 7-day phenytoin (prophylaxis group) and 61 receiving no prophylaxis (observation group). The incidence of all seizures was 18% in the observation group and 24% in the prophylaxis group (p = 0.51). Importantly, the incidence of early seizures (< 30 days after surgery) was 8% in the observation group compared with 10% in the prophylaxis group (p = 1.0). Likewise, the incidence of clinically significant early seizures was 3% in the observation group and 2% in the prophylaxis group (p = 0.62). The prophylaxis group experienced significantly more adverse events (18% vs 0%, p < 0.01). Therapeutic phenytoin levels were maintained in 80% of patients.

Conclusions

The incidence of seizures after surgery for brain tumors is low (8% [95% CI 3%–18%]) even without prophylactic AEDs, and the incidence of clinically significant seizures is even lower (3%). In contrast, routine phenytoin administration is associated with significant drug-related morbidity. Although the lower-than-anticipated incidence of seizures in the control group significantly limited the power of the study, the low baseline rate of perioperative seizures in patients with brain tumors raises concerns about the routine use of prophylactic phenytoin in this patient population.

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Xiang Y. Han, Jeffrey S. Weinberg, Sujit S. Prabhu, Samuel J. Hassenbusch, Gregory N. Fuller, Jeffrey J. Tarrand and Dimitrios P. Kontoyiannis

Object. The cases of five patients with fusobacterial brain abscess are presented. The authors discuss their attempt to determine the pathogenesis.

Methods. The clinical and microbiological features of five cases of fusobacterial brain abscess are reviewed. Isolates of 2031 Fusobacterium spp. and other anaerobes collected (1989–2002) at our institution were analyzed and compared for incidences and isolation sources. The findings were correlated with extensive literature on the subject.

The five patients were men between 45 and 74 years of age. All experienced an insidious onset of the disease and probable hematogenous seeding of the organism(s). One patient had a monomicrobic Fusobacterium necrophorum abscess, whereas the others had polymicrobic F. nucleatum abscesses. Despite surgery and a regimen of antibiotic medications and dexamethasone, three patients experienced a paradoxical deterioration 3 days postoperatively that necessitated reevacuation of the lesion. The evacuants observed at that time contained numerous leukocytes but no microorganisms, suggesting intensified inflammation as the likely cause of deterioration. This explanation is supported by literature that fusobacteria strongly activate neutrophils. An analysis of the 2031 anaerobes from blood, wounds, and abscesses showed the considerable virulence of Fusobacterium spp., which were able to enter and/or sustain themselves in the blood circulation. This pattern was similar to that of Clostridium spp., but different from those of Peptostreptococcus spp., Bacteroides spp., and Prevotella spp., which were less invasive but more abundant.

Conclusions. Some fusobacterial brain abscesses may be associated with a paradoxical postoperative deterioration, which is probably due to intensified inflammation following treatment. The blood-borne dissemination and invasive behavior of fusobacteria likely initiate such a brain abscess, and further seeding of other synergic bacteria leads to a polymicrobic abscess.

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William C. Broaddus, Sujit S. Prabhu, George T. Gillies, Jeffrey Neal, William S. Conrad, Zhi-Jian Chen, Helen Fillmore and Harold F. Young

High-flow microinfusion is a novel technique for delivery of compounds directly into the brain parenchyma, bypassing the blood-brain barrier. The feasibility of this technique has been demonstrated with low-molecular-weight compounds, macromolecular dyes, and proteins. Delivery of antisense oligonucleotides into the brain parenchyma represents an additional potential application of this technique not previously described. In this report, the authors examined the distribution and disposition of phosphorothioate oligodeoxynucleotide (PS-ODN) infused for this reason. An 18-mer 35S-PS-ODN (molecular weight approximately 6000) was infused over 1 hour into the caudate putamen of Fischer 344 rats. At 1, 6, 12, 24, and 48 hours after beginning the infusion, the brains were extracted and analyzed using quantitative autoradiographic techniques. Cerebrospinal fluid (CSF) was also aspirated from the cisterna magna and analyzed for radioactivity and stability of the 35S-PS-ODN. At 1 hour, the infused ODN was uniformly distributed in brain tissue, with a maximum average concentration of 4806.5 ± 210.5 nCi/g. This represents a tissue concentration of 19.2 ± 0.84 μM. Extensive spread into surrounding parenchyma was observed over the ensuing 47 hours. The 35S-PS-ODN radioactivity peaked in the CSF at the end of the 1-hour infusion, containing 10% (50 ± 20 nCi) of the infused radioactivity. Activity then decayed exponentially over 11 hours, stabilizing at a lower CSF content of 0.2% (1 ± 0.1 nCi). The volume of distribution (Vd) was 105 ± 7.9 mm3 at 1 hour, representing a ratio of Vd/Vi (volume of infusion) of 5.2. The Vd increased to 443.4 ± 62.3 mm3 at the end of 48 hours, whereas the average minimum tissue concentration decreased from 15.2 to 3.2 μM. Undegraded 18-mer was seen throughout the 48-hour period using 20% polyacrylamide/7M urea gel electrophoresis. The animals tolerated the infusion without evidence of toxicity, and minimal structural changes in tissue were observed on histological examination. Thus, PS-ODN can be safely delivered in high concentrations to wide areas of the rat brain by using high-flow microinfusion, and the concentrations remain stable even after 48 hours in situ.

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William C. Broaddus, Sujit S. Prabhu, George T. Gillies, Jeffrey Neal, William S. Conrad, Zhi-Jian Chen, Helen Fillmore and Harold F. Young

Object. High-flow microinfusion is a novel technique for delivery of compounds directly into brain parenchyma, bypassing the blood-brain barrier. The feasibility of this technique has been demonstrated with low-molecular-weight compounds, macromolecular dyes, and proteins. Delivery of antisense oligonucleotides into brain parenchyma represents an additional potential application of this technique not previously described. In this report the authors sought to examine the distribution and disposition of phosphorothioate oligodeoxynucleotide (PS-ODN) for this reason.

Methods. An 18-mer 35S-PS-ODN (M r approximately 6000) was infused over 1 hour into the caudate putamen of Fischer 344 rats. At 1, 6, 12, 24, and 48 hours after beginning the infusion, the brains were extracted and analyzed using quantitative autoradiographic techniques. Cerebrospinal fluid (CSF) was also aspirated from the cisterna magna and was analyzed to determine the radioactivity and stability of the 35S-PS-ODN. At 1 hour, the infused ODN was uniformly distributed in brain tissue, with a maximum average concentration of 4806.5 ± 210.5 nCi/g. This represents a tissue concentration of 19.2 ± 0.84 µM. Extensive spread into surrounding parenchyma was observed over the ensuing 47 hours. The 35S-PS-ODN radioactivity peaked in the CSF at the end of the 1-hour infusion, containing 1% (50 ± 20 nCi) of the infused radioactivity. Activity then decayed exponentially over 11 hours, but stabilized at a lower CSF content of 0.2% (1 ± 0.1 nCi) thereafter. The volume of distribution was 105 ± 7.9 mm3 at 1 hour, representing a volume of distribution/volume of infusion ratio of 5.2. The volume of distribution increased to 443 ± 62.3 mm3 at the end of 48 hours, whereas the average minimum tissue concentration decreased from 15.2 µM to 3.2 µM. Undegraded 18-mer was observed throughout the 48-hour period by means of 20% polyacrylamide/7 M urea gel electrophoresis. The animals tolerated the infusion without evidence of toxicity and minimal structural changes in tissue were observed on histological investigation.

Conclusions. The authors found that PS-ODNs can be safely delivered in high concentrations to wide areas of rat brain by using high-flow microinfusion and are stable even after 48 hours in situ.