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Lucia Schwyzer, Robert M. Starke, John A. Jane Jr. and Edward H. Oldfield

OBJECT

Correlation between tumor volume and hormone levels in individual patients would permit calculation of the fraction of tumor removed by surgery, by measuring postoperative hormone levels. The goals of this study were to examine the relationship between tumor volume, growth hormone (GH), and insulin-like growth factor–1 (IGF-1) levels, and to assess the correlation between percent tumor removal and the reduction in plasma GH and IGF-1 in patients with acromegaly.

METHODS

The 3D region of interest–based volumetric method was used to measure tumor volume via MRI before and after surgery in 11 patients with GH-secreting adenomas. The volume of residual tumor as a fraction of preoperative tumor volume was correlated with GH levels before and after surgery. Examination of this potential correlation required selection of patients with acromegaly who 1) had incomplete tumor removal, 2) had precise measurements of initial and residual tumor, and 3) were not on medical therapy.

RESULTS

Densely granulated tumors produced more peripheral GH per mass of tumor than sparsely granulated tumors (p = 0.04). There was a correlation between GH and IGF-1 levels (p = 0.001). Although there was no close correlation between tumor size and peripheral GH levels, after normalizing each tumor to its own plasma GH level and tumor volume, a comparison of percent tumor resection with percent drop in plasma GH yielded a high correlation coefficient (p = 0.006).

CONCLUSIONS

Densely granulated somatotropinomas produce more GH per mass of tumor than do sparsely granulated tumors. Each GH-secreting tumor has its own intrinsic level of GH production per mass of tumor, which is homogeneous over the tumor mass, and which varies greatly between tumors. In most patients the fraction of a GH-secreting tumor removed by surgery can be accurately estimated by simply comparing plasma GH levels after surgery to those before surgery.

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Robert M. Starke, John A. Jane Jr., Ashok R. Asthagiri and John A. Jane Sr.

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Allan D. Levi, Robert M. Starke, Ricardo J. Komotar and Robert E. Harbaugh

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Robert M. Starke, Brian J. Williams, John A. Jane Jr. and Jason P. Sheehan

Object

Nonfunctioning pituitary macroadenomas often recur after microsurgery and thereby require further treatment. Gamma Knife surgery (GKS) has been used to treat recurrent adenomas. In this study, the authors evaluated outcomes following GKS of nonfunctioning pituitary macroadenomas and assessed predictors of tumor control, neurological deficits, and delayed hypopituitarism.

Methods

Between June 1989 and March 2010, 140 consecutive patients with nonfunctioning pituitary macroadenomas were treated using GKS at the University of Virginia. The median patient age was 51 years (range 21–82 years), and 56% of patients were male. Mean tumor volume was 5.6 cm3 (range 0.6–35 cm3). Thirteen patients were treated with GKS as primary therapy, and 127 had undergone at least 1 open resection prior to GKS. Ninety-three patients had a history of hormone therapy prior to GKS. The mean maximal dose of GKS was 38.6 Gy (range 10–70 Gy), the mean marginal dose was 18 Gy (range 5–25 Gy), and the mean number of isocenters was 9.8 (range 1–26). Follow-up evaluations were performed in all 140 patients, ranging from 0.5 to 17 years (mean 5 years, median 4.2 years).

Results

Tumor volume remained stable or decreased in 113 (90%) of 125 patients with available follow-up imaging. Kaplan-Meier analysis demonstrated radiographic progression free survival at 2, 5, 8, and 10 years to be 98%, 97%, 91%, and 87%, respectively. In multivariate analysis, a tumor volume greater than 5 cm3 (hazard ratio = 5.0, 95% CI 1.5–17.2; p = 0.023) was the only factor predictive of tumor growth. The median time to tumor progression was 14.5 years. Delayed hypopituitarism occurred in 30.3% of patients. No factor was predictive of post-GKS hypopituitarism. A new or worsening cranial nerve deficit occurred in 16 (13.7%) of 117 patients. Visual decline was the most common neurological deficit (12.8%), and all patients experiencing visual decline had evidence of tumor progression. In multivariate analysis, a tumor volume greater than 5 cm3 (OR = 3.7, 95% CI 1.2–11.7; p = 0.025) and pre-GKS hypopituitarism (OR = 7.5, 95% CI 1.1–60.8; p = 0.05) were predictive of a new or worsened neurological deficit.

Conclusions

In patients with nonfunctioning pituitary macroadenomas, GKS confers a high rate of tumor control and a low rate of neurological deficits. The most common complication following GKS is delayed hypopituitarism, and this occurs in a minority of patients.

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Robert M. Starke, Chun-Po Yen, Dale Ding and Jason P. Sheehan

Object

The authors performed a study to review outcomes following Gamma Knife radiosurgery for cerebral arteriovenous malformations (AVMs) and to create a practical scale to predict long-term outcome.

Methods

Outcomes were reviewed in 1012 patients who were followed up for more than 2 years. Favorable outcome was defined as AVM obliteration and no posttreatment hemorrhage or permanent, symptomatic, radiation-induced complication. Preradiosurgery patient and AVM characteristics predictive of outcome in multivariate analysis were weighted according to their odds ratios to create the Virginia Radiosurgery AVM Scale.

Results

The mean follow-up time was 8 years (range 2–20 years). Arteriovenous malformation obliteration occurred in 69% of patients. Postradiosurgery hemorrhage occurred in 88 patients, for a yearly incidence of 1.14%. Radiation-induced changes occurred in 387 patients (38.2%), symptoms in 100 (9.9%), and permanent deficits in 21 (2.1%). Favorable outcome was achieved in 649 patients (64.1%). The Virginia Radiosurgery AVM Scale was created such that patients were assigned 1 point each for having an AVM volume of 2–4 cm3, eloquent AVM location, or a history of hemorrhage, and 2 points for having an AVM volume greater than 4 cm3. Eighty percent of patients who had a score of 0–1 points had a favorable outcome, as did 70% who had a score of 2 points and 45% who had a score of 3–4 points. The Virginia Radiosurgery AVM Scale was still predictive of outcome after controlling for predictive Gamma Knife radiosurgery treatment parameters, including peripheral dose and number of isocenters, in a multivariate analysis. The Spetzler-Martin grading scale and the Radiosurgery-Based Grading Scale predicted favorable outcome, but the Virginia Radiosurgery AVM Scale provided the best assessment.

Conclusions

Gamma Knife radiosurgery can be used to achieve long-term AVM obliteration and neurological preservation in a predictable fashion based on patient and AVM characteristics.

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Erin N. Kiehna, Robert M. Starke, Nader Pouratian and Aaron S. Dumont

Object

The Consolidated Standards for Reporting of Trials (CONSORT) criteria were published in 1996 to standardize the reporting and improve the quality of clinical trials. Despite having been endorsed by major medical journals and shown to improve the quality of reported trials, neurosurgical journals have yet to formally adopt these reporting criteria. The purpose of this study is to evaluate the quality and reporting of randomized controlled trials (RCTs) in neurosurgery and the factors that may affect the quality of reported trials.

Methods

The authors evaluated all neurosurgical RCTs published in 2006 and 2007 in the principal neurosurgical journals (Journal of Neurosurgery; Neurosurgery; Surgical Neurology; Journal of Neurology, Neurosurgery, and Psychiatry; and Acta Neurochirurgica) and in 3 leading general medical journals (Journal of the American Medical Association, Lancet, and the New England Journal of Medicine). Randomized controlled trials that addressed operative decision making or the treatment of neurosurgical patients were included in this analysis. The RCT quality was evaluated using the Jadad score and the CONSORT checklist.

Results

In 2006 and 2007, 27 RCTs relevant to intracranial neurosurgery were reported. Of these trials, only 59% had a Jadad score ≥ 3. The 3 major medical journals all endorsed the CONSORT guidelines, while none of the neurosurgical journals have adopted these guidelines. Randomized controlled trials published in the 3 major medical journals had a significantly higher mean CONSORT score (mean 41, range 39–44) compared with those published in neurosurgical journals (mean 26.4, range 17–38; p < 0.0001). Jadad scores were also significantly higher for the major medical journals (mean 3.42, range 2–5) than neurosurgical journals (mean 2.45, range 1–5; p = 0.05).

Conclusions

Despite the growing volume of RCTs in neurosurgery, the quality of reporting of these trials remains suboptimal, especially in the neurosurgical journals. Improved awareness of the CONSORT guidelines by journal editors, reviewers, and authors of these papers could improve the methodology and reporting of RCTs in neurosurgery.

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Stephen J. Monteith, Robert M. Starke, John A. Jane Jr. and Edward H. Oldfield

Object

Subnormal postoperative serum cortisol levels indicate successful surgery and predict long-term remission of Cushing disease. Given the short serum half-lives of adrenocorticotropic hormone (ACTH) and cortisol, it is unclear why the decline in cortisol postoperatively is delayed for 18–36 hours. Furthermore, the relevance of the rate of cortisol drop immediately after surgery has not been investigated.

Methods

Patient data were analyzed from a prospectively accrued database. After surgery, cortisol replacement was withheld and serum cortisol measurements were obtained every 6 hours until values of 1.0–2.0 μg/dl or less were reached. The authors selected patients in whom serum cortisol dropped to 2 μg/dl or less after surgery (101 patients). Tumor resection was categorized as follows: 1) complete resection using the histological pseudocapsule as a surgical capsule, 2) complete piecemeal resection), 3) known incomplete resection, and 4) total hypophysectomy.

Results

The median time to reach a cortisol level of less than or equal to 2.0 μg/dl was 9.9, 19.4, 25.3, and 29.5 hours with hypophysectomy, pseudocapsule, incomplete resection, and piecemeal techniques, respectively. Pseudocapsule resection produced a faster decline in cortisol than piecemeal techniques (p = 0.0001), but not as rapid a decline as hypophysectomy (p = 0.033).

Conclusions

Complete resection by other techniques is associated with delayed cortisol decline compared with pseudocapsule surgery, which may represent the product of residual tumor cells and therefore may explain the higher rate of recurrent disease associated with piecemeal techniques. The prompt drop in cortisol after hypophysectomy compared with patients with pseudocapsule surgery suggests that the corticotrophs of the normal gland can secrete ACTH for 10–36 hours after surgery despite prolonged and severe hypercortisolism.

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Robert M. Starke, Justin M. Cappuzzo, Nicholas J. Erickson and Jonathan H. Sherman

OBJECTIVE

Cystic lesions of the pineal gland are most often uncomplicated benign lesions with typical MRI characteristics. The authors aimed to study pineal lesion characteristics on MRI to better distinguish benign pineal cysts from other pineal region malignancies as well as to determine which characteristics were predictive of the latter malignancies. They also aimed to study risk factors predictive of hydrocephalus or malignancy in patients harboring these lesions.

METHODS

The authors performed a retrospective review of a prospectively compiled database documenting the outcomes of patients with suspected pineal cysts on MRI who had presented in the period from 1998 to 2004. Inherent patient and lesion characteristics were assessed in a univariate logistic regression analysis to predict the following dependent variables: development of hydrocephalus, biopsy-confirmed malignancy, and intervention. Possible inherent patient and lesion characteristics included age, sex, T1 and T2 MRI signal pattern, contrast enhancement pattern, presence of cyst, presence of blood, complexity of lesion, presence of calcification, and duration of follow-up. Inherent patient and lesion characteristics that were predictive in the univariate analysis (p < 0.15) were included in the multivariable logistic regression analysis.

RESULTS

Of the 79 patients with benign-appearing pineal cysts, 26 (33%) were male and 53 (67%) were female, with a median age of 38 years (range 9–86 years). The median cyst radius was 5 mm (range 1–20 mm). Two patients (2.5%) had evidence of calcifications, 7 (9%) had multicystic lesions, and 25 (32%) had some evidence of contrast enhancement.

The median follow-up interval was 3 years (range 0.5–13 years). Seven patients (9%) had an increase in the size of their lesion over time. Eight patients (10%) had a hemorrhage, and 11 patients (14%) developed hydrocephalus. Nine (11%) received ventriculoperitoneal shunts for the development of hydrocephalus, and 12 patients (16%) were found to have malignancies following biopsy or resection. In the multivariate analysis, contrast enhancement on MRI (OR 1.6, 95% CI 2.86–74.74, p = 0.013) and hemorrhage (OR 26.9, 95% CI 3.4–212.7, p = 0.022) were predictive of hydrocephalus. Increasing lesion size and hydrocephalus were near perfect predictors of malignancy and thus were removed from multivariate analysis. In addition, contrast enhancement on MRI (OR 8.8, 95% CI 2.0–38.6, p = 0.004) and hemorrhage (OR 6.8, 95% CI 1.1–40.5, p = 0.036) were predictive of malignancy.

CONCLUSIONS

Although cystic abnormalities of the pineal gland are often benign lesions, they are frequently monitored over time, as other pineal region pathologies may appear similarly on MRI. Patients with growing lesions, contrast enhancement, and hemorrhage on MRI are more likely to develop hydrocephalus and have malignant pathology on histological examination and should therefore be followed up with serial MRI with a lower threshold for neurosurgical intervention.