Bilateral ultrasound-guided supraclavicular block in a patient with severe electrocution injuries of the upper extremities.

The performance of bilateral supraclavicular brachial plexus nerve blocks is controversial. We present the challenging case of a 29-year-old male who suffered bilateral high-voltage electrocution injuries to the upper extremities, resulting in severe tissue damage, sensory and motor deficits, and wounds in both axillae. This injury necessitated bilateral below-elbow amputations. His postoperative course was complicated by pain refractory to intravenous narcotics. The decision was made to attempt bilateral supraclavicular brachial plexus blocks. Our concerns with this approach included the risks of pneumothorax and respiratory failure due to phrenic nerve block. Initial attempts at brachial plexus blockade using nerve stimulation were unsuccessful; therefore, ultrasound guidance was employed. With vigilant monitoring in an intensive care unit setting, we were able to safely perform bilateral continuous supraclavicular brachial plexus nerve blocks with an excellent analgesic response and no noted complications.

Intraoperative and Postoperative Blood Glucose Concentrations in Diabetic Surgical Patients Receiving Lactated Ringer's Versus Normal Saline: A Retrospective Review of Medical Records.

BACKGROUND: Hyperglycemia is associated with poor postoperative outcomes after carotid endarterectomy. This retrospective study examined the effect of lactated Ringer's and normal saline solutions on intraoperative blood glucose control in diabetic patients undergoing carotid endarterectomy. METHODS: The anesthetic and surgical records of type 2 diabetic patients who underwent carotid endarterectomy and received either lactated Ringer's solution or normal saline exclusively during the case were reviewed, and 20 patients were randomly selected from each group for further analysis. The outcome of interest was preoperative to postoperative change in blood glucose. RESULTS: The preoperative to postoperative mean changes in glucose for the normal saline and lactated Ringer's groups were 34.4 ± 70.32 mg/dL and 64.5 ± 61.38 mg/dL, respectively. This slight difference in the mean change in glucose between the 2 groups was not statistically significant (P=0.157). CONCLUSION: Lactated Ringer's solution does not appear to cause a significant change in the mean blood glucose levels in diabetic patients undergoing carotid endarterectomy compared to patients receiving normal saline. Randomized controlled trials are needed to further determine whether lactated Ringer's solution adversely affects glucose control in diabetic surgical patients.

Mandibular advancement for obstructive sleep apnea: relating outcomes to anatomy.

IMPORTANCE: This study provides insight into the response and cure rates of oral appliances (OAs) in patients with primary retropalatal, retroglossal, or retroepiglottic obstruction, as well as the effect of minimal cross-sectional area on the overall decrease in the apnea-hypopnea index (AHI) across all anatomical locations of collapse. OBJECTIVE: To examine the role of regional upper airway obstruction measured with acoustic pharyngometry as a determinant of OA success. DESIGN, SETTING, AND PARTICIPANTS: This retrospective case-series included patients with obstructive sleep apnea-hypopnea syndrome at a tertiary care center. INTERVENTIONS: Patients were fitted with a custom OA between July 1, 2011, and January 1, 2012. MAIN OUTCOMES AND MEASURES: Regions of maximal upper airway collapse were determined on acoustic pharyngometry: retropalatal, retroglossal, or retroepiglottic. Apnea-hypopnea index improvement at titration polysomnography was assessed against regional collapse. RESULTS: Seventy-five patients (56 [75%] men; mean [SD] age, 49.0 [13.6] years; mean body mass index [calculated as weight in kilograms divided by height in meters squared], 29.4 [5.2]; and mean AHI, 30.6 [20.0]) were assessed, and data were grouped on the basis of region of maximal collapse at pharyngometry (retropalatal in 29 patients, retroglossal in 28, and retroepiglottic in 18). The overall reduction in AHI at OA titration showed no significant difference between groups. There was no significant difference in the response rate to treatment, defined as more than 50% AHI reduction plus an AHI of less than 20 (response rate, 69% for retropalatal, 75% for retroglossal, and 83% for retroepiglottic collapse; P = .55) or the cure rate, defined as an AHI of less than 5 (cure rate, 52% for retropalatal, 43% for retroglossal, and 72% for retroepiglottic collapse; P = .15). The correlation between minimal cross-sectional area and response trended toward significance (r = 0.20; range -0.03 to 0.41; P < .10). CONCLUSIONS AND RELEVANCE: Oral appliance therapy achieves reasonable response and cure rates in patients with primary retropalatal, retroglossal, or retroepiglottic obstruction at the time of initial titration polysomnography. However, success is not predicted by identification of the region of maximal upper airway collapse measured with acoustic pharyngometry.

Diagnosis of obstructive sleep apnea by peripheral arterial tonometry: meta-analysis.

IMPORTANCE: Efficient diagnosis and early treatment of obstructive sleep apnea may help prevent the development of related morbidity and mortality. Compared with polysomnography (PSG), ambulatory sleep study devices offer the possibility of an accurate diagnosis with convenience and low cost. OBJECTIVE: To assess the correlation between sleep indexes measured by a portable sleep-testing device (peripheral arterial tonometry [PAT]) and those measured by PSG. DATA SOURCES: We searched PubMed, MEDLINE, the Cochrane Trial Registry (through May 2013), and relevant article bibliographies. STUDY SELECTION: Systematic review and meta-analysis of studies assessing correlation of sleep indexes between PAT devices and PSG in adults (aged >18 years). Included studies provided a bivariate correlation coefficient for sleep indexes, specifically the respiratory disturbance index (RDI), apnea-hypopnea index (AHI), and oxygen desaturation index (ODI). DATA EXTRACTION AND SYNTHESIS: Included studies were reviewed by 2 independent reviewers. Reported correlation values for the RDI, AHI, and ODI between a commercially available PAT device (WatchPAT) and PSG were systematically reviewed. A comprehensive meta-analysis software package was used for statistical analysis. MAIN OUTCOMES AND MEASURES: Assessment of the correlation between PAT and PSG as measured by AHI, RDI, and ODI. RESULTS: Fourteen studies met inclusion criteria and had data suitable for pooling (909 patients). Of these, 13 studies had blinded study designs, with PAT and PSG conducted simultaneously in the home or the laboratory setting. One study contained 2 trial phases for the same patient group (n = 29), one laboratory based and the other home based, which were analyzed separately. One study contained 2 different study groups based on age. Overall, correlation of the RDI and AHI was high (r = 0.889 [95% CI, 0.862-0.911]; P < .001). Studies comparing the RDI between PAT and PSG had a combined correlation of 0.879 (95% CI, 0.849-0.904; P < .001); those comparing the AHI, 0.893 (0.857-0.920; P < .001); and those comparing the ODI, 0.942 (0.894-0.969; P < .001). Analysis of publication bias revealed a nonsignificant Egger regression intercept. CONCLUSIONS AND RELEVANCE: Respiratory indexes calculated using PAT-based portable devices positively correlated with those calculated from the scoring of PSG. Strengthened by the blinded design of most of the included studies, this technology represents a viable alternative to PSG for confirmation of clinically suspected sleep apnea.

Effects of Pillar implants for sleep-related breathing disorders on middle ear function.

Pillar implants provide a reasonable outcome with minimal post-operative morbidity and complications in treating patients with sleep-disordered breathing (SDB) who had obvious palatal obstruction. The palatal structure is responsible for a normal functioning Eustachian tube; however, little is known if there is any potential otologic implication of minimally invasive palatal stiffening surgery for SDB. The aim of this study is to evaluate the effects of Pillar implantation on middle ear function. We performed a prospective study in a tertiary referral center. Thirty SDB patients (25 men, 5 women; mean age, 44.3 years) who underwent Pillar implants for treating palatal obstruction were enrolled. The subjects had normal otologic exam and no previous history of chronic ear disease. Pure-tone audiometry and tympanometry were performed pre-operatively, and post-operative days 1 and 7, and months 1 and 3. Baseline and post-operative middle ear pressures (MEPs) in decipascals were compared. Statistical analysis was performed by repeated measures of ANOVA. Eight patients (8/30, 26.7%) reported otologic complaints such as ear pressure and/or otalgia within 1 week post-operatively. No permanent otologic discomfort occurred. A trend toward reduced MEP was noted in this study. The decrease in MEP became apparent on post-operative day 1 after surgery. However, mean pressure changes were no longer significantly different from pre-operative values by 1 week after surgery. Pillar implantation for SDB induces changes in middle ear function. However, the changes were temporary and not significant 1 week after surgery.

Diagnostic value of the Friedman tongue position and Mallampati classification for obstructive sleep apnea: a meta-analysis.

OBJECTIVE: To assess the association between the Mallampati classification and Friedman tongue position for obstructive sleep apnea severity as determined by apnea-hypopnea index and to determine which method is most closely correlated with prediction of obstructive sleep apnea severity. DATA SOURCES: English-language searches of PubMed, MedLine, and the Cochrane database. Reference sections of identified studies were examined for additional articles. REVIEW METHODS: Databases through December 2011 were searched, combined with review of relevant article bibliographies, and assessed by 4 reviewers. Systematic review and random-effects meta-analysis of studies evaluating tongue position and obstructive sleep apnea severity were performed. Outcomes were reported as correlations. RESULTS: Ten studies met inclusion criteria and had data for pooling (2513 patients). Friedman tongue position and Mallampati classification were significantly associated with obstructive sleep apnea severity, with a correlation of 0.351 (0.094-0.564, P = .008). Analysis of the correlation of tongue position with obstructive sleep apnea severity reveals correlations of 0.184 (0.052, 0.310, P = .006) and 0.388 (0.049, 0.646, P = .026) for the Mallampati classification and Friedman tongue position, respectively. Publication bias does not yield a significant Egger regression intercept; however, 4 imputed values to the right of the mean were found using Duval and Tweedie's trim-and-fill method, yielding an overall correlation of 0.498 (confidence interval = 0.474-0.521). CONCLUSION: The Mallampati classification and Friedman tongue position assessment techniques are significantly correlated with predicting obstructive sleep apnea severity. Publication bias does not significantly affect our results. The strength of this correlation is higher for Friedman tongue position, although 95% confidence intervals for the respective correlation coefficients overlap.

Effect of continuous positive airway pressure on C-reactive protein levels in sleep apnea: a meta-analysis.

OBJECTIVE: Evaluate the effects of continuous positive airway pressure (CPAP) on C-reactive protein (CRP) levels, reported either as a primary or secondary end point among patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) based on a meta-analysis of published studies. DATA SOURCES: English-language searches of PubMed, Ovid, and the Cochrane databases were completed. Reference sections of identified studies were also examined for additional relevant articles to review. REVIEW METHODS: Studies of adult patients with OSAHS who reported pre- and post-CPAP treatment CRP were reviewed and analyzed. Two independent reviewers extracted data from 10 peer-reviewed studies, which were combined using a random effects meta-analysis model. RESULTS: The CPAP treatment was found to lead to a significant reduction in CRP levels (17.8%, P = .002). This corresponds to an effect size of -0.485 (-0.731, -0.240). Sensitivity analysis was done to determine the impact of study design. Both case-control studies and case-series studies yielded a significant effect. Sensitivity analysis also yielded a significant effect for studies with average body mass index <30, studies where CPAP was employed over automatic positive airway pressure, and studies treating patients ≤ 3 months. Analysis of publication bias, however, revealed a likelihood of "missing" studies. CONCLUSION: Although there is a significant lack of high-quality studies addressing this question, this analysis suggests that treatment with CPAP leads to a statistically significant reduction in CRP levels. However, the mean pre- and posttreatment CRP levels observed are considered "high risk" for cardiovascular morbidity. The clinical significance of this finding as it relates to cardiovascular risk reduction and the relationship between CRP and OSAHS requires further study.

Modified adenotonsillectomy to improve cure rates for pediatric obstructive sleep apnea: a randomized controlled trial.

OBJECTIVE: To compare the efficacy of adenotonsillectomy (T&A) with and without pharyngoplasty (tonsillar pillar closure) in the treatment of pediatric obstructive sleep apnea-hypopnea syndrome (OSAHS). STUDY DESIGN: Randomized single-blind controlled study. SETTING: Tertiary care center. SUBJECTS AND METHODS: Sixty pediatric patients with a clinical diagnosis of OSAHS presenting between January 2009 and December 2010 were enrolled and randomized to undergo either standard T&A (n = 30) or T&A with pharyngoplasty (n = 30). Surgical cure was defined as apnea-hypopnea index (AHI) <5 plus OSA-18 health-related quality-of-life (HRQL) score <60. Other outcomes included postsurgical AHI and minimum oxygen saturation (SpO(2)) improvement, changes in OSA-18 scores at 1 month, and postsurgical days to resume normal diet and activity. RESULTS: Three patients from each group did not undergo surgery. Of the 54 patients treated, 8 from the pharyngoplasty group and 2 from the standard group were lost to follow-up. Intention-to-treat analysis revealed no difference in cure rate between groups (standard 60%, pharyngoplasty 56.6%, P = .793). Limiting analysis to those patients with complete data, a higher, but not significantly increased, cure rate with pharyngoplasty was noted (72% vs 89.5%, P = .155). Greater OSA-18 improvement (P = .036) and greater (although nonsignificant) AHI improvement and earlier return to normal function were noted with pharyngoplasty. CONCLUSION: The addition of pharyngoplasty to traditional adenotonsillectomy did not significantly improve OSAHS cure rates as measured by sleep testing and HRQL, although a nonsignificant increase in cure rate was observed in those who completed the study protocol. An unexpectedly high rate of patient dropout rendered the study statistically underpowered and therefore inconclusive.

Compliance and efficacy of titratable thermoplastic versus custom mandibular advancement devices.

OBJECTIVE: To share our experiences treating patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) with titratable thermoplastic (TPD) and custom-made mandibular advancement devices (MAD) and to compare these devices in terms of objective improvement and cure and treatment success (improvement/cure plus adherence at 6 months). STUDY DESIGN: Case series with planned data collection. SETTING: Tertiary care center. SUBJECTS AND METHODS: Patients with OSAHS who failed or refused both continuous positive airway pressure (CPAP) and surgery had a titratable oral appliance fitted. Patients were offered an office-fitted TPD or a custom-made dentist-fitted device. Assessment included pretreatment and appliance-titration polysomnography (PSG). Improvement was defined as ≥ 50% apnea-hypopnea index (AHI) reduction plus posttreatment AHI <20, and cure was defined as AHI <5. Patients were contacted at 1 and 6 months regarding treatment adherence. RESULTS: A total of 180 patients (123 TPD, 57 custom) with complete PSG data were reviewed. Improvement/cure were significantly better with the custom device overall (91.2%/71.9% vs 77.2%/52.0%, P = .024/.012). Adherence data at 1 and 6 months were obtained from 128/180 and 119/180 patients, respectively. Using an intention-to-treat analysis, those lost to follow-up were considered nonadherent. Adherence at 1/6 months was 64.9%/50.9% for custom versus 53.7%/32.5% for TPD (P = .156/.018), yielding treatment success rates (with initial improvement/cure) of 49.1%/40.4% for custom versus 27.6%/17.1% for TPD (P = .005/<.001) at 6 months. CONCLUSION: Custom-fit devices achieve higher rates of objective improvement and cure of OSAHS than TPD at the time of titration-PSG. TPDs have a high acceptance rate, low cost, and reasonable initial improvement and cure rates of 77.2% and 52.0%, respectively, but significantly poorer 6-month compliance.

The value of routine pH monitoring in the diagnosis and treatment of laryngopharyngeal reflux.

OBJECTIVE: To assess the need for pH testing in diagnosing laryngopharyngeal reflux (LPR). STUDY DESIGN: Case series with planned data collection. SETTING: Tertiary care center. SUBJECTS AND METHODS: On the basis of symptoms and/or abnormal endoscopic findings, more than 500 patients underwent 24-hour pharyngeal pH testing at a single center (using the Dx-pH probe) between January 2009 and June 2011. A total of 163 patients not on proton-pump inhibitors at the time of study and with complete data available for analysis (pH results, body mass index, smoking status, pretest reflux symptom index) were divided into 2 groups by positive (n = 70) and negative (n = 93) Ryan Score. The Reflux Symptom Index (RSI) was compared between groups and assessed overall against Ryan Score parameters at different pH thresholds. The diagnostic utility of an RSI ≥ 13 for prediction of Ryan Score was assessed. RESULTS: No significant difference in RSI was seen between Ryan-positive (17.50 ± 11.47) and Ryan-negative (14.95 ± 11.43) patients (P = .161). Overall, RSI correlated poorly with percentage time spent below pH thresholds 6.5, 6.0, 5.5, and 5.0 and upright and supine Ryan parameters at these thresholds (as determined by linear regression analysis). The sensitivity, specificity, positive predictive value, and negative predictive value of RSI ≥ 13 for Ryan positivity were 55.7%, 47.3%, 44.3%, and 58.7%, respectively. CONCLUSION: Our findings show that in our population of otolaryngology patients, the diagnosis of LPR cannot be reliably made on the basis of symptoms alone. Diagnosis, and in particular treatment decisions, should ideally be made on the basis of a combination of symptoms, signs, and confirmatory testing.

Dead Sea salt irrigations vs saline irrigations with nasal steroids for symptomatic treatment of chronic rhinosinusitis: a randomized, prospective double-blind study.

BACKGROUND: Intranasal steroids are 1 of the most frequently prescribed medications for the treatment of chronic rhinosinusitis (CRS), and saline irrigations are commonly used as an adjunct to medical therapy. We aimed to compare the efficacy of Dead Sea salt (DSS) irrigations and DSS nasal spray vs saline irrigations and topical nasal steroid spray in the treatment of symptoms of CRS. METHODS: A total of 145 symptomatic adult patients without acute infection were initially enrolled and 114 completed the study. Patients completed a Sino-Nasal Outcomes Test 20 (SNOT-20) survey (primary outcome metric) and underwent endonasal examination, acoustic rhinometry, and smell testing (secondary outcome metrics). Patients were randomized to 2 groups. The experimental group (n = 59) self-administered hypertonic DSS spray and DSS irrigation; the control group (n = 55) self-administered fluticasone spray and hypertonic saline irrigation and spray. Patients and staff were blinded to group assignment. Outcomes were reassessed at 4 weeks. RESULTS: The 2 groups were homogeneous with respect to pretreatment primary and secondary outcome metrics. Dropout rates were 30% in the DSS group and 36.6% in the control group. Both groups showed significant improvement in mean SNOT-20 scores following treatment; however, the degree of improvement was not significantly different between groups (p = 0.082). There were no significant changes in secondary outcome metrics between the 2 groups. CONCLUSION: For patients with CRS, treatment with DSS irrigations and sprays appears as effective for symptom reduction as a combination of hypertonic saline irrigations and sprays and a topical steroid spray.

Transoral robotic glossectomy for the treatment of obstructive sleep apnea-hypopnea syndrome.

OBJECTIVE: In previous reports of transoral robotic surgery (TORS) for the treatment of obstructive sleep apnea-hypopnea syndrome (OSAHS), patients underwent routine tracheotomy. We aim to assess the feasibility of performing robotically assisted partial glossectomy without tracheotomy and to assess efficacy by comparing OSAHS outcomes with those of established techniques. STUDY DESIGN: Historical cohort study with planned data collection. SETTING: Tertiary care center. SUBJECTS AND METHODS: Forty consecutive patients underwent TORS for OSAHS between October 2010 and June 2011 and were followed up with regard to complications, morbidity, and subjective and objective outcomes. Data from 27 of these patients who underwent concomitant z-palatoplasty with 6-month follow-up were compared with those of 2 matched cohorts of patients, who underwent either radiofrequency (radiofrequency base-of-tongue reduction [RFBOT]) or coblation (submucosal minimally invasive lingual excision [SMILE]) reduction of the tongue base and z-palatoplasty. RESULTS: No major bleeding or airway complications were observed. Postoperative pain and length of admission were similar between groups. All groups saw Epworth score and snore score improvement. Patients undergoing robot-assisted surgery took longer than their SMILE and RFBOT counterparts to tolerate normal diet and longer than RFBOT patients to resume normal activity. Apnea hypopnea index (AHI) reduction averaged 60.5% ± 24.9% for TORS versus 37.0% ± 51.6% (P = .042) and 32.0% ± 43.3% (P = .012) for SMILE and RFBOT, respectively. Only the robotic group achieved statistically significant improvement in minimum oxygen saturation. Surgical cure rate for TORS (66.7%) was significant compared with RFBOT (20.8%, P = .001) but not compared with SMILE (45.5%, P = .135). CONCLUSION: Robotically assisted partial glossectomy feasibly can be performed without the need for tracheotomy. This technique resulted in greater AHI reduction but increased morbidity compared with the other techniques studied.

Aberrant angiogenic characteristics of human brain arteriovenous malformation endothelial cells.

OBJECTIVE: To identify and characterize the phenotypic and functional differences of endothelial cells derived from cerebral arteriovenous malformations (AVM), as compared with endothelial cells derived from a normal brain. METHODS: Isolated AVM brain endothelial cells and control brain endothelial cells were evaluated immunohistochemically for expression of the endothelial cell markers von Willebrand factor and CD31, as well as angiogenic factors including vascular endothelial growth factor A, interleukin-8, and endothelin-1. Vascular endothelial growth factor receptors 1 and 2 were also evaluated using immunohistochemistry techniques. Functional assays evaluated cell proliferation, cytokine production, tubule formation, and cell migration using the modified Boyden chamber technique. RESULTS: Endothelial cells derived from AVMs expressed high levels of vascular endothelial growth factor A and significantly overexpressed the vascular endothelial growth factor receptors 1 and 2 (P < 0.05), as compared with control endothelial cells. In addition, comparison to control brain endothelial cells demonstrated that AVM brain endothelial cells proliferated faster, migrated more quickly, and produced aberrant tubule-like structures. CONCLUSION: Endothelial cells derived from cerebral AVMs are highly activated cells overexpressing proangiogenic growth factors and exhibiting abnormal functions consistent with highly activated endothelial cells.

Therapeutic vaccination against malignant gliomas based on allorecognition and syngeneic tumor antigens: proof of principle in two strains of rat.

In the present study we investigated whether allogeneic glioma cells can be utilized to evoke prophylactic or therapeutic immune-mediated elimination of syngeneic glioma in two rat strains. Fisher 344 and Sprague-Dawley (SD) rats were injected with two syngeneic glioma cell lines, 9L and C6, respectively, resulting in progressive tumor growth. 9L is syngeneic to the Fisher 344 and allogeneic to the SD rats, while C6 cells are syngeneic to SD rats and allogeneic to Fisher 344 rats. Both rat strains were subcutaneously injected with their respective allogeneic tumor cells, which proved unable to grow progressively. The allogeneic cells were either rejected immediately in SD rats or within 25 days in Fisher rats, after limited tumor outgrowth. Both rat strains were subsequently challenged with their respective syngeneic glioma tumor cells and once more 10 days later with a fivefold higher dose. SD rats, even after reinjection with five times the original dosage of C6 cells, remained tumor free for at least 360 days. Similarly, Fisher rats, after initially rejecting allogeneic tumors, failed to develop syngeneic tumors. To determine anti-tumor immunity against established glioma tumors under more demanding therapeutic conditions, rats were first injected subcutaneously with their respective syngeneic tumor and vaccinated once or repeatedly (at 5-day intervals) with a mixture of the allogeneic or xenogeneic cells, with or without a lysate from the same syngeneic tumor, which served as a therapeutic vaccine preparations. The control group received either no treatment or syngeneic instead of allogeneic cells. In both strains of rats, we demonstrated that the therapeutically vaccinated groups were able to significantly reduce tumor growth, while complete rejection of tumors was noted in the SD rats. Immunization with syngeneic tumor cells alone failed to evoke anti-tumor immunity. We conclude that therapeutic immunization with a combination of allogeneic cells and syngeneic lysates induces rejection of malignant gliomas and offers a protective effect against challenge with syngeneic tumor cells. This immunization approach may prove useful as a post-surgery adjuvant therapy in future cancer treatment protocols, or even as a stand-alone therapeutic tumor vaccination.

Irinotecan: a potential new chemotherapeutic agent for atypical or malignant meningiomas.

OBJECT: There is currently no effective chemotherapy for meningiomas. Although most meningiomas are treated surgically, atypical or malignant meningiomas and surgically inaccessible meningiomas may not be removed completely. The authors have investigated the effects of the topoisomerase I inhibitor irinotecan (CPT-11) on primary meningioma cultures and a malignant meningioma cell line in vitro and in vivo. METHODS: The effects of irinotecan on cellular proliferation in primary meningioma cultures and the IOMM-Lee malignant meningioma cell line were measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide assay and flow cytometry. Apoptosis following drug treatment was evaluated by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling and the DNA laddering assays. The effects of irinotecan in vivo on a meningioma model were determined with a subcutaneous murine tumor model using the IOMM-Lee cell line. Irinotecan induced a dose-dependent antiproliferative effect with subsequent apoptosis in the primary meningioma cultures (at doses up to 100 microM) as well as in the IOMM-Lee human malignant meningioma cell line (at doses up to 20 microM) irinotecan. In the animal model, irinotecan treatment led to a statistically significant decrease in tumor growth that was accompanied by a decrease in Bcl-2 and survivin levels and an increase in apoptotic cell death. CONCLUSIONS: Irinotecan demonstrated growth-inhibitory effects in meningiomas both in vitro and in vivo. Irinotecan was much more effective against the malignant meningioma cell line than against primary meningioma cultures. Therefore, this drug may have an important therapeutic role in the treatment of atypical or malignant meningiomas and should be evaluated further for this purpose.