Search Results

You are looking at 1 - 10 of 20 items for

  • Author or Editor: Jon D. Weingart x
Clear All Modify Search
Restricted access

Jon D. Weingart, Eric P. Sipos and Henry Brem

✓ This study was designed to explore the question of whether minocycline, a semisynthetic tetracycline shown to inhibit tumor-induced angiogenesis, could control the growth of the rat intracranial 9L gliosarcoma. Minocycline was tested alone and in combination with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) in vivo. Treatment was started at the time of intracranial implantation of 9L gliosarcoma into male Fischer 344 rats, 5 days later, or after tumor resection.

Minocycline was delivered locally with a controlled-release polymer or systemically by intraperitoneal injection. Systemic minocycline did not extend survival time. Local treatment with minocycline by a controlled-release polymer implanted at the time of tumor implantation extended median survival time by 530% (p < 0.001) compared to treatment with empty polymer. When treatment was begun 5 days after tumor implantation, minocycline delivered locally or systemically had no effect on survival. However, after tumor resection, treatment with locally delivered minocycline resulted in a 43% increase in median survival time (p < 0.002) compared to treatment with empty polymer. Treatment with a combination of minocycline delivered locally in a controlled-release polymer and systemic BCNU 5 days after tumor implantation resulted in a 93% extension of median survival time compared to BCNU alone (p < 0.002). In contrast, treatment with a combination of systemic minocycline and BCNU did not increase survival time compared to systemic BCNU alone. These results demonstrate that minocycline affects tumor growth when delivered locally and suggest that minocycline may be a clinically effective modulator of intracranial tumor growth when used in combination with a chemotherapeutic agent and surgical resection.

Restricted access

Benjamin S. Carson, Jon D. Weingart, Michael Guarnieri and Paul G. Fisher

✓ This 9-year-old boy with a history of behavioral problems and worsening psychosis responded initially to treatment with haloperidol. However, a magnetic resonance image obtained as part of his psychiatric evaluation revealed an anterior third ventricle tumor and mild-to-moderate hydrocephalus. The resected tumor was found on pathological examination to be a choroid plexus papilloma. The patient had an uneventful postoperative course and remained free of psychosis or mood disorder at 1-year follow-up examination.

Restricted access

Graeme F. Woodworth, Matthew J. McGirt, Amer Samdani, Ira Garonzik, Alessandro Olivi and Jon D. Weingart

Object

The gold standard for stereotactic brain biopsy target localization has been frame-based stereotaxy. Recently, frameless stereotactic techniques have become increasingly utilized. Few authors have evaluated this procedure, analyzed preoperative predictors of diagnostic yield, or explored the differences in diagnostic yield and morbidity rate between the frameless and frame-based techniques.

Methods

A consecutive series of 110 frameless and 160 frame-based image-guided stereotactic biopsy procedures was reviewed. Associated variables for both techniques were reviewed and compared. All stereotactic biopsy procedures were included in a risk factor analysis of nondiagnostic biopsy sampling.

Frameless stereotaxy led to a diagnostic yield of 89%, with a total permanent morbidity rate of 6% and a mortality rate of 1%. Larger lesions were fivefold more likely to yield diagnostic tissues. Deep-seated lesions were 2.7-fold less likely to yield diagnostic tissues compared with cortical lesions. Frameless compared with frame-based stereotactic biopsy procedures showed no significant differences in diagnostic yield or transient or permanent morbidity. For cortical lesions, more than one needle trajectory was required more frequently to obtain diagnostic tissues with frame-based as opposed to frameless stereotaxy, although this factor was not associated with morbidity.

Conclusions

With regard to diagnostic yield and complication rate, the frameless stereotactic biopsy procedure was found to be comparable to or better than the frame-based method. Smaller and deep-seated lesions together were risk factors for a nondiagnostic tissue yield. Frameless stereotaxy may represent a more efficient means of obtaining biopsy specimens of cortical lesions but is otherwise similar to the frame-based technique.

Restricted access

Henry Brem, Rafael J. Tamargo, Alessandro Olivi, Michael Pinn, Jon D. Weingart, Moody Wharam and Jonathan I. Epstein

✓ Sustained drug delivery by biodegradable polymer devices can increase the therapeutic efficacy of drugs by producing high local tissue concentrations over extended periods of time. It has been shown previously that implantation of controlled-release polymers impregnated with the nitrosourea carmustine (BCNU) extended the period of survival in rats bearing the 9L glioma compared with similar rats treated with systemically administered BCNU. This study evaluated the effect on the monkey brain of interstitial delivery of BCNU by the biodegradable polyanhydride copolymer poly[bis(p-carboxyphenoxy)propane]anhydride (PCPP) and sebacic acid (SA) in a 20:80 formulation (PCPP:SA). The effect of combining interstitial BCNU with radiation therapy was also evaluated. Eighteen male cynomologus monkeys were randomly assigned to one of four groups: a control group; a group with implantation of empty polymer; a group with implantation of BCNU-loaded polymer; and a group with implantation of empty polymer in the right hemisphere and BCNU-loaded polymer in the left hemisphere, followed by irradiation. The effects were evaluated radiologically and histologically at specified times. A local reaction by the brain to the polymer was found, which was greater when the polymer contained BCNU. Local cerebral edema was observed radiographically on postoperative Day 14 and had resolved by Day 72. Histologically, a subacute cellular inflammatory response was seen on postoperative Day 16, which had changed to a chronic inflammatory response by Day 72. In the group with radiation therapy administered to the hemisphere bearing BCNU-loaded polymer, only localized pathological changes were detected. In all animals, brain distant from the polymer implantation site was normal. No neurological or general deleterious effects were seen in any of the animals. It is concluded that the interstitial delivery of BCNU by the polyanhydride polymer PCPP:SA is safe in the primate brain and that concomitant radiation therapy did not lead to any adverse effects. These experimental findings are important to an understanding of the clinical effects of PCPP:SA implants in treating brain diseases.

Restricted access

Kaisorn L. Chaichana, Khan K. Chaichana, Alessandro Olivi, Jon D. Weingart, Richard Bennett, Henry Brem and Alfredo Quiñones-Hinojosa

Object

As the population ages, the incidence of glioblastoma multiforme (GBM) among older patients (age > 65 years) will increase. Older patients, unlike their younger counterparts, are not often offered aggressive surgery because of their age, comorbidities, and potential inability to tolerate surgery. The goal of this study was to identify preoperative factors associated with decreased survival for older patients who underwent resection of a GBM. The identification of these factors may provide insight into which patients would benefit most from aggressive surgery.

Methods

All patients older than 65 years who underwent nonbiopsy resection of an intracranial GBM at a single institution between 1997 and 2007 were retrospectively reviewed. Factors associated with overall survival were assessed using multivariate proportional hazards regression analysis after controlling for peri- and postoperative factors known to be associated with outcome (extent of resection, carmustine wafer implantation, temozolomide chemotherapy, and radiation therapy). Variables with p < 0.05 were considered statistically significant.

Results

A total of 129 patients with an average age of 73 ± 5 years met the inclusion/exclusion criteria. At last follow-up, all 129 patients had died, with a median survival of 7.9 months. The preoperative factors that were independently associated with decreased survival were Karnofsky Performance Scale (KPS) score less than 80 (p = 0.001), chronic obstructive pulmonary disease (p = 0.01), motor deficit (p = 0.01), language deficit (p = 0.005), cognitive deficit (p = 0.02), and tumor size larger than 4 cm (p = 0.002). Patients with 0–1 (Group 1), 2–3 (Group 2), and 4–6 (Group 3) of these factors had statistically different survival times, where the median survival was 9.2, 5.5, and 4.4 months, respectively. In log-rank analysis, the median survival for Group 1 was significantly longer than that for Group 2 (p = 0.004) and Group 3 (p < 0.0001), while Group 2 had longer survival than Group 3 (p = 0.02).

Conclusions

Older patients with an increasing number of these factors may not benefit as much from aggressive surgery as patients with fewer factors. This may provide insight into identifying which patients older than 65 years of age may benefit from aggressive surgery.

Restricted access

Kaisorn L. Chaichana, Aditya N. Halthore, Scott L. Parker, Alessandro Olivi, Jon D. Weingart, Henry Brem and Alfredo Quinones-Hinojosa

Object

The median survival duration for patients with glioblastoma is approximately 12 months. Maximizing quality of life (QOL) for patients with glioblastoma is a priority. An important, yet understudied, QOL component is functional independence. The aims of this study were to evaluate functional outcomes over time for patients with glioblastoma, as well as identify factors associated with prolonged functional independence.

Methods

All patients who underwent first-time resection of either a primary (de novo) or secondary (prior lower grade glioma) glioblastoma at a single institution from 1996 to 2006 were retrospectively reviewed. Patients with a Karnofsky Performance Scale (KPS) score ≥ 80 were included. Kaplan-Meier, log-rank, and multivariate proportional hazards regression analyses were used to identify associations (p < 0.05) with functional independence (KPS score ≥ 60) following glioblastoma resection.

Results

The median follow-up duration time was 10 months (interquartile range [IQR] 5.6–17.0 months). A patient's preoperative (p = 0.02) and immediate postoperative (within 2 months) functional status was associated with prolonged survival (p < 0.0001). Of the 544 patients in this series, 302 (56%) lost their functional independence at a median of 10 months (IQR 6–16 months). Factors independently associated with prolonged functional independence were: preoperative KPS score ≥ 90 (p = 0.004), preoperative seizures (p = 0.002), primary glioblastoma (p < 0.0001), gross-total resection (p < 0.0001), and temozolomide chemotherapy (p < 0.0001). Factors independently associated with decreased functional independence were: older age (p < 0.0001), coexistent coronary artery disease (p = 0.009), and incurring a new postoperative motor deficit (p = 0.009). Furthermore, a decline in functional status was independently associated with tumor recurrence (p = 0.01).

Conclusions

The identification and consideration of these factors associated with prolonged functional outcome (preoperative KPS score ≥ 90, seizures, primary glioblastoma, gross-total resection, temozolomide) and decreased functional outcome (older age, coronary artery disease, new postoperative motor deficit) may help guide treatment strategies aimed at improving QOL for patients with glioblastoma.

Restricted access

Kaisorn L. Chaichana, Thomas Kosztowski, Ashwini Niranjan, Alessandro Olivi, Jon D. Weingart, John Laterra, Henry Brem and Alfredo Quiñones-Hinojosa

Object

Patients harboring anaplastic astrocytomas (AAs) typically have a poor prognosis, with median survival times of approximately 3 years following resection. However, a significant variability in individual outcomes remains, with some patients surviving for a few months and others for several years. The ability to predict patient outcomes based on preoperative variables would help prognosticate survival and may also guide treatment strategies. The prognostic implications of a preoperative contrast-enhancing AA remain poorly understood.

Methods

The medical records of all patients who underwent a craniotomy for a hemispheric AA from 1996 to 2006 at a single institution were retrospectively reviewed. Multivariate proportional hazards regression analysis was used to identify independent associations with recurrence and survival. The Kaplan-Meier method and log-rank analysis were used to plot and compare outcomes for patients with and without preoperative contrast enhancement.

Results

One hundred sixty-five patients were available for analysis. The AAs were contrast enhancing in 102 patients (62%), and nonenhancing in 63 patients (38%). There were no significant differences in clinical and treatment-related variables between patients with and without contrast enhancement. After multivariate analysis, contrast enhancement was independently associated with decreased survival (p = 0.02) and increased recurrence (p = 0.04). The 5-year overall survival rates for patients with contrast-enhancing versus nonenhancing tumors were 31 and 38.5%, respectively. The 3-year rates of progression-free survival for patients with contrast-enhancing versus nonenhancing tumors were 32 and 56%, respectively. Interestingly, heterogeneously enhancing tumors appear to result in poorer outcomes as compared with other types of enhancement (such as ring enhancing, nodular, and others). Among patients with contrast-enhancing AAs, gross-total resection significantly delayed recurrence (p = 0.05) but did not significantly prolong survival (p = 0.52).

Conclusions

This study may provide insights into risk-stratifying patients with AAs, and most specifically those with AAs that enhance with contrast administration.

Restricted access

Matthew J. McGirt, Frank J. Attenello, Ghazala Datoo, Muraya Gathinji, April Atiba, Jon D. Weingart, Benjamin Carson and George I. Jallo

Object

Indications for duraplasty in treatment of Chiari malformation Type I (CM-I) remain unclear. In the present study, the authors evaluate their surgical experience to determine whether intraoperative ultrasonography is effective in the selection of patients with CM-I who can be adequately treated with craniectomy alone without duraplasty.

Methods

The authors reviewed the records of 256 children who underwent first-time hindbrain decompression for CM-I. Craniectomy alone (without duraplasty) was performed when intraoperative ultrasonography suggested adequate decompression of the subarachnoid spaces ventral and dorsal to the tonsils after suboccipital craniectomy alone. Duraplasty was performed if intraoperative ultrasonography demonstrated persistent dural compression of the tonsils following craniectomy. Symptom recurrence as a function of time was compared between cases of duraplasty versus suboccipital decompression alone stratified by extent of tonsillar herniation.

Results

Duraplasty was performed in 140 patients (55%), and suboccipital decompression alone was performed in 116 patients (45%). Patients underwent follow-up for 29 ± 15 months. Symptoms included headache in 192 patients (75%) and lower cranial nerve and brainstem dysfunction in 68 (27%). In 38 patients (15%) there was tonsillar herniation rostral to the C-1 lamina, in 195 (76%) it extended between the C-1 and C-2 lamina, and in 23 patients (9%) there was herniation caudal to the lower border of the C-2 lamina. In children with tonsillar herniation caudal to C-1, ultrasonography-guided suboccipital decompression alone was associated with a 2-fold increase in the risk of symptom recurrence compared with those who also underwent duraplasty (p = 0.01). In children with tonsillar herniation rostral to C-1, outcome was equivalent between suboccipital decompression alone and duraplasty (p = 0.41).

Conclusions

In the setting of moderate-to-severe tonsillar CM-I, intraoperative ultrasonography demonstrating decompression of the subarachnoid spaces ventral and dorsal to the tonsils may not effectively select patients in whom bone decompression alone is sufficient. Duraplasty may be warranted in cases of tonsillar herniation that extends below the C-1 lamina regardless of intraoperative ultrasonography findings. More objective cerebrospinal fluid flow or volumetric measures may be needed intraoperatively to guide duraplasty in patients with more pronounced tonsillar herniation.

Restricted access

Athir H. Morad, Bradford D. Winters, Myron Yaster, Robert D. Stevens, Elizabeth D. White, Richard E. Thompson, Jon D. Weingart and Allan Gottschalk

Object

Opioid administration following major intracranial surgery is often limited by a presumed lack of need and a concern that opioids will adversely affect postoperative outcome and interfere with the neurological examination. Nevertheless, evidence is accumulating that these patients suffer moderate to severe postoperative pain and that this pain is often undertreated. The authors hypothesized that intravenous patient-controlled analgesia (PCA) would safely and more effectively treat postoperative supratentorial craniotomy pain than conventional as needed (PRN) therapy.

Methods

Following a standardized course of general anesthesia, adult patients who underwent elective supratentorial intracranial surgery were randomized in the neurosciences intensive care unit to receive either PRN intravenous fentanyl 25–50 μg every 30 minutes or PCA intravenous fentanyl 0.5 μg/kg every 15 minutes (maximum 4 doses/hour). The authors measured pain (self-reported scale score [0–10]), sedation (Ramsay Sedation Scale score), Glasgow Coma Scale score, fentanyl use, and major adverse events (excessive sedation, respiratory depression, pruritus, nausea, or vomiting) hourly.

Results

Sixty-four patients with a mean age of 48 years (range 22–77 years) were randomized to intravenous PCA (29 patients) or PRN fentanyl (35 patients) groups. There were no statistically significant demographic differences between the 2 groups. Patients receiving intravenous PCA had significantly lower pain scores than those receiving intravenous PRN fentanyl (2.53 ± 1.96 vs 3.62 ± 2.11 [p = 0.039]) and received significantly more fentanyl than the PRN group (44.1 ± 34.5 vs 23.6 ± 23.7 μg/hour [p = 0.007]). There were no differences between the 2 groups regarding the number of patients with adverse events.

Conclusions

Intravenous PCA more effectively treats the pain of supratentorial intracranial surgery than PRN fentanyl, and patients in the former group did not experience any untoward events related to the self-administration of opioids.

Restricted access

Allan Gottschalk, Lauren C. Berkow, Robert D. Stevens, Marek Mirski, Richard E. Thompson, Elizabeth D. White, Jon D. Weingart, Donlin M. Long and Myron Yaster

Object

Opioid administration after major intracranial surgery is often limited by a presumed lack of need and a concern that opioids will adversely affect the postoperative neurological examination. The authors conducted a prospective study to evaluate the incidence, severity, and treatment of postoperative pain in patients who underwent major intracranial surgery.

Methods

One hundred eighty-seven patients (77 men and 110 women, mean age 52 ± 15 years, mean weight 78.1 ± 19.9 kg) underwent either supratentorial (129 patients) or infratentorial (58 patients) procedures. Sixty-nine percent of the patients reported experiencing moderate to severe pain (≥ 4 on a 0–10 scale) during the 1st postoperative day. Pain scores greater than or equal to 4 persisted in 48% on the 2nd postoperative day. Approximately 80% of patients were treated with acetaminophen on the 1st postoperative day, whereas opioids (primarily intravenous fentanyl) were administered to 58%. Compared with patients who underwent supratentorial procedures, those who underwent infratentorial procedures reported more severe pain at rest (mean score 4.9 ± 2.2 compared with 3.8 ± 2.6; p = 0.015) and with movement (mean score 6.3 ± 2.6 compared with 4.5 ± 2.7; p < 0.001) on the 1st postoperative day. On both the 1st and 2nd postoperative days, patients who underwent infratentorial procedures received greater quantities of opioid (p ≤ 0.019) and nonopioid (p ≤ 0.013) analgesics than those who underwent supratentorial procedures. Patients’ dissatisfaction with analgesic therapy was significantly associated with elevated pain levels on the first 2 postoperative days (p < 0.001).

Conclusions

In contrast to prevailing assumptions, the study findings reveal that most patients undergoing elective major intracranial surgery will experience moderate to severe pain for the first 2 days after surgery and that this pain is often inadequately treated.