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Yan Michael Li, Dima Suki, Kenneth Hess and Raymond Sawaya


Glioblastoma multiforme (GBM) is the most common and deadliest primary brain tumor. The value of extent of resection (EOR) in improving survival in patients with GBM has been repeatedly confirmed, with more extensive resections providing added advantages. The authors reviewed the survival of patients with significant EORs and assessed the relative benefit/risk of resecting 100% of the MRI region showing contrast-enhancement with or without additional resection of the surrounding FLAIR abnormality region, and they assessed the relative benefit/risk of performing this additional resection.


The study cohort included 1229 patients with histologically verified GBM in whom ≥ 78% resection was achieved at The University of Texas MD Anderson Cancer Center between June 1993 and December 2012. Patients with > 1 tumor and those 80 years old or older were excluded. The survival of patients having 100% removal of the contrast-enhancing tumor, with or without additional resection of the surrounding FLAIR abnormality region, was compared with that of patients undergoing 78% to < 100% EOR of the enhancing mass. Within the first subgroup, the survival durations of patients with and without resection of the surrounding FLAIR abnormality were subsequently compared. The data on patients and their tumor characteristics were collected prospectively. The incidence of 30-day postoperative complications (overall and neurological) was noted.


Complete resection of the T1 contrast-enhancing tumor volume was achieved in 876 patients (71%). The median survival time for these patients (15.2 months) was significantly longer than that for patients undergoing less than complete resection (9.8 months; p < 0.001). This survival advantage was achieved without an increase in the risk of overall or neurological postoperative deficits and after correcting for established prognostic factors including age, Karnofsky Performance Scale score, preoperative contrast-enhancing tumor volume, presence of cyst, and prior treatment status (HR 1.53, 95% CI 1.33–1.77, p < 0.001). The effect remained essentially unchanged when data from previously treated and previously untreated groups of patients were analyzed separately. Additional analyses showed that the resection of ≥ 53.21% of the surrounding FLAIR abnormality beyond the 100% contrast-enhancing resection was associated with a significant prolongation of survival compared with that following less extensive resections (median survival times 20.7 and 15.5 months, respectively; p < 0.001). In the multivariate analysis, the previously treated group with < 53.21% resection had significantly shorter survival than the 3 other groups (that is, previously treated patients who underwent FLAIR resection ≥ 53.21%, previously untreated patients who underwent FLAIR resection < 53.21%, and previously untreated patients who underwent FLAIR resection ≥ 53.21%); the previously untreated group with ≥ 53.21% resection had the longest survival.


What is believed to be the largest single-center series of GBM patients with extensive tumor resections, this study supports the established association between EOR and survival and presents additional data that pushing the boundary of a conventional 100% resection by the additional removal of a significant portion of the FLAIR abnormality region, when safely feasible, may result in the prolongation of survival without significant increases in overall or neurological postoperative morbidity. Additional supportive evidence is warranted.

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Christopher S. Rumana, Kenneth R. Hess, Wei Ming Shi and Raymond Sawaya

Object. Twenty-two patients who had solitary metastatic brain tumors with dural extension were treated surgically over a 3-year period. Their cases were reviewed to characterize these lesions and to compare the patients with a similar cohort in which there was no dural involvement.

Methods. The median age of the patients was 58 years (range 11–68 years) and the male/female ratio was 12:10. The median preoperative Karnofsky Performance Scale (KPS) score in the group was 90 (range 70–100). The most common histological diagnoses seen in these patients included breast cancer, adenocarcinoma and squamous cell carcinoma of the lung, and renal cell carcinoma. All patients underwent gross-total resection of the tumor and 86% received radiation therapy. The median patient survival time was 11 months, with a median time to recurrent intracranial disease of 19 months. Survival was related to the histological diagnosis. Recurrent disease occurred in 41% of cases. Leptomeningeal disease occurred in three patients (14%). The frequency and time course of development of recurrent disease was not affected by dural resection nor was survival.

These results for patients having metastatic brain tumors with dural extension were compared with those for a cohort of 26 patients in which there were similar histological diagnosis, age, gender, and preoperative KPS score were distributed similarly but in which each patient had a single subcortical metastatic lesion. Those patients had a median survival of 10 months and the median time to recurrence was not reached. Leptomeningeal disease occurred in one patient (4%).

Conclusions. To the authors' knowledge, this is the first reported series of patients with metastatic brain tumors with dural extension. Patients with this disease may be more likely to develop recurrences along the dura and leptomeningeal disease, but the overall survival time in these patients is not different from those patients with intraparenchymal lesions.

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Frederick F. Lang, Raymond Sawaya, Dima Suki, Ian E. McCutcheon and Kenneth R. Hess

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Rajesh K. Bindal, Raymond Sawaya, Milam E. Leavens, Kenneth R. Hess and Sarah H. Taylor

✓ Results of reoperation in 48 patients who developed recurrent brain metastases between January 1984 and April 1993 are presented. Median time from first craniotomy to diagnosis of recurrence (time to recurrence) was 6.7 months. Median Karnofsky performance scale (KPS) score prior to reoperation was 80. Recurrence was local in 30 patients, distant in 16 patients, and both local and distant in two patients. Median survival time after reoperation was 11.5 months. There were no operative mortalities. Multivariate analysis revealed that presence of systemic disease (p = 0.008), KPS scores less than or equal to 70 (p = 0.008), time to recurrence of less than 4 months (p = 0.008), age greater than or equal to 40 years (p = 0.51), and primary tumor type of breast or melanoma (p = 0.028) negatively affected patient survival time. These five factors were used to develop a grading system (Grades I–IV). Patients categorized in Grade I had a 5-year survival rate of 57%, whereas the median survival time of patients in Grades II, III, and IV was 13.4, 6.8, and 3.4 months, respectively (p < 0.0001).

Overall, 26 patients developed a second recurrence after reoperation. Seventeen patients underwent a second reoperation, whereas nine did not. Patients undergoing a second reoperation survived a median of 8.6 additional months versus 2.8 months for those who did not (p < 0.0001).

This study concludes that reoperation for recurrent brain metastasis can prolong survival and improve quality of life. A second reoperation can also increase survival. Five factors influence survival: status of systemic disease, KPS score, time to recurrence, age, and type of primary tumor. The grading system using these five factors correlates with survival time. Reoperation should be approached with caution in Grade IV patients because of their poor prognosis.

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Ajay K. Bindal, Rajesh K. Bindal, Kenneth R. Hess, Almon Shiu, Samuel J. Hassenbusch, Wei Ming Shi and Raymond Sawaya

✓ Surgery and radiosurgery are effective treatment modalities for brain metastasis. To compare the results of these treatment modalities, the authors followed 31 patients treated by radiosurgery and 62 patients treated by surgery who were retrospectively matched. Patients were matched according to the following criteria: histological characteristics of the primary tumor, extent of systemic disease, preoperative Karnofsky Performance Scale score, time to brain metastasis, number of brain metastases, and patient age and sex. For patients treated by radiosurgery, the median size of the treated lesion was 1.96 cm3 (range 0.41–8.25 cm3) and the median dose was 20 Gy (range 12–22 Gy). The median survival was 7.5 months for patients treated by radiosurgery and 16.4 months for those treated by surgery; this difference was found to be statistically significant using both univariate (p = 0.0018) and multivariate (p = 0.0009) analyses. The difference in survival was due to a higher rate of mortality from brain metastasis in the radiosurgery group than in the surgery group (p < 0.0001) and not due to a difference in the rate of death from systemic disease (p = 0.28). Log-rank analysis showed that the higher mortality rate found in the radiosurgery group was due to a greater progression rate of the radiosurgically treated lesions (p = 0.0001) and not due to the development of new brain metastasis (p = 0.75).

On the basis of their data, the authors conclude that surgery is superior to radiosurgery in the treatment of brain metastasis. Patients who undergo surgical treatment survive longer and have a better local control. The data lead the authors to suggest that the indications for radiosurgery should be limited to surgically inaccessible metastatic tumors or patients in poor medical condition. Surgery should remain the treatment of choice whenever possible.

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George A. Younis, Raymond Sawaya, Franco DeMonte, Kenneth R. Hess, Steffen Albrecht and Janet M. Bruner

✓ A series of 25 patients with aggressive meningeal tumors was studied to determine the efficacy of various management options. The median age of the patients was 52 years, with a range of 13 to 73 years. A marked male preponderance (64%) was noted. Twenty of 25 patients experienced recurrence during a median follow-up time of 47 months. Survival and freedom from recurrence varied with histological diagnosis. Recurrence was noted sooner in patients who had received partial resections on first presentation of tumor than in those who had received total resections at first presentation. Survival time was also shorter for patients who underwent partial resections at first presentation than for patients who underwent total resections.

Patients' prognoses did not improve as a result of either chemotherapy or radiotherapy. Of six patients with extracranial metastases, the median time to metastasis was 102 months, with a 5-year metastasis-free rate of 85%. The most common sites of metastasis in these six patients were lung and bone. In each tumor type, histological features used in diagnosis and radiological features studied from computerized tomography and magnetic resonance imaging were evaluated, compared, and discussed. Of eight patients studied with an in vivo bromodeoxyuridine (BUdR) labeling index (LI), seven showed an LI of 1% or more. The authors support the incorporation of the BUdR LI into the diagnostic process to provide a better estimate of the potential for tumor recurrence.

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Justin M. Cappuzzo, Ryan M. Hess, John F. Morrison, Jason M. Davies, Kenneth V. Snyder, Elad I. Levy and Adnan H. Siddiqui


Idiopathic intracranial hypertension (IIH) is a commonly occurring disease, particularly among young women of child-bearing age. The underlying pathophysiology for this disease has remained largely unclear; however, the recent literature suggests that focal outflow obstruction of the transverse sinus may be the cause. The purpose of this study was to report one group’s early experience with transverse venous sinus stenting in the treatment of IIH and assess its effectiveness.


The authors performed a retrospective chart review to identify patients who had undergone stenting of an outflow-obstructed transverse venous sinus for the treatment of IIH at Gates Vascular Institute between January 2015 and November 2017. Patient demographic data of interest included age, sex, BMI, and history of smoking, hypertension, obstructive sleep apnea, hormonal contraceptive use, and acetazolamide therapy. Each patient’s presenting signs and symptoms and whether those symptoms improved with treatment were reviewed. The average opening lumbar puncture (LP) pressure preprocedure, average pressure gradient across the obstructed segment prior to stenting, treatment failure rate (need for shunt placement), and mean follow-up period were calculated.


Of the 18 patients who had undergone transverse venous stenting for IIH, 16 (88.9%) were women. The mean age of all the patients was 38.3 years (median 38 years). Mean BMI was 34.2 kg/m2 (median 33.9 kg/m2). Presenting symptoms were headache (16 patients [88.9%]), visual disturbances (13 patients [72.2%]), papilledema (8 patients [44.4%]), tinnitus (3 patients [16.7%]), and auditory bruit (3 patients [16.7%]). The mean opening LP pressure pre-procedure was 35.6 cm H2O (median 32 cm H2O). The mean pressure gradient measured proximally and distally to the area of focal obstruction within the transverse sinus was 16.5 cm H2O (median 15 cm H2O). Postprocedurally, 14 patients (77.8%) continued to have headaches; 6 (33.3%) continued to have visual disturbances. No patients continued to have auditory bruit (0%) or papilledema (0%). One patient (5.6%) had new-onset tinnitus postprocedure. Overall improvement of symptoms was noted in 16 patients (88.9%) postprocedure, with 1 patient (5.6%) requiring shunt placement and 2 other patients (11.1%) requiring postprocedural LP to monitor intracranial pressure to determine candidacy for further surgical interventions to treat residual symptoms. The mean duration of follow-up was 194.2 days.


Transverse sinus stenting is a rapidly developing technique that has shown good effectiveness and safety in the literature. Authors of the present study found that stenting a flow-obstructed transverse sinus in patients with IIH was a safe and effective way to treat the condition.

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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


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.


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.


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.


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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Michel Lacroix, Dima Abi-Said, Daryl R. Fourney, Ziya L. Gokaslan, Weiming Shi, Franco DeMonte, Frederick F. Lang, Ian E. McCutcheon, Samuel J. Hassenbusch, Eric Holland, Kenneth Hess, Christopher Michael, Daniel Miller and Raymond Sawaya

Object. The extent of tumor resection that should be undertaken in patients with glioblastoma multiforme (GBM) remains controversial. The purpose of this study was to identify significant independent predictors of survival in these patients and to determine whether the extent of resection was associated with increased survival time.

Methods. The authors retrospectively analyzed 416 consecutive patients with histologically proven GBM who underwent tumor resection at the authors' institution between June 1993 and June 1999. Volumetric data and other tumor characteristics identified on magnetic resonance (MR) imaging were collected prospectively.

Conclusions. Five independent predictors of survival were identified: age, Karnofsky Performance Scale (KPS) score, extent of resection, and the degree of necrosis and enhancement on preoperative MR imaging studies. A significant survival advantage was associated with resection of 98% or more of the tumor volume (median survival 13 months, 95% confidence interval [CI] 11.4–14.6 months), compared with 8.8 months (95% CI 7.4–10.2 months; p < 0.0001) for resections of less than 98%. Using an outcome scale ranging from 0 to 5 based on age, KPS score, and tumor necrosis on MR imaging, we observed significantly longer survival in patients with lower scores (1–3) who underwent aggressive resections, and a trend toward slightly longer survival was found in patients with higher scores (4–5). Gross-total tumor resection is associated with longer survival in patients with GBM, especially when other predictive variables are favorable.