Randomized Controlled Trial of a Cohesive Eight-Week Evolution Unit That Incorporates Molecular Genetics and Principles of the Next Generation Science Standards.

In response to calls for curricular materials that integrate molecular genetics and evolution and adhere to the K-12 Next Generation Science Standards (NGSS), the Genetic Science Learning Center (GSLC) at the University of Utah has developed and tested the "Evolution: DNA and the Unity of Life" curricular unit for high school biology. The free, 8-week unit illuminates the underlying role of molecular genetics in evolution while providing scaffolded opportunities to engage in making arguments from evidence and analyzing and interpreting data.  We used a randomized controlled trial design to compare student learning when using the new unit with a condition in which teachers used their typical (NGSS-friendly) units with no molecular genetics. Results from nationwide testing with 38 teachers (19 per condition) and their 2269 students revealed that students who used the GSLC curriculum had significantly greater pre/post gain scores in their understanding of evolution than students in the comparison condition; the effect size was moderate. Further, teacher implementation data suggest that students in the treatment condition had more opportunities to engage in argumentation from evidence and have in-class discussions than students in the comparison classes. We consider study implications for the secondary and postsecondary science education community.

Anesthetic management of an obstetric patient with MELAS syndrome: case report and literature review.

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS syndrome) is a mitochondrial disorder associated with neurologic, cardiac, neuromuscular, hepatic, metabolic and gastrointestinal dysfunction and potential anesthetic and obstetric complications. The case of a parturient with MELAS syndrome requiring labor analgesia is presented. A Medline literature search limited to the English language was undertaken to review cases of MELAS syndrome. Based on our experience and literature review, parturients with MELAS syndrome appear to benefit from neuraxial analgesia and anesthesia, which blunt excessive oxygen consumption and acidosis.

A phase I/II study to evaluate the toxicity and efficacy of accelerated fractionation radiotherapy for the palliation of dysphagia from carcinoma of the oesophagus.

AIMS: We hypothesised that accelerated fractionated radiotherapy may provide a good palliative approach for dysphagia relief in patients with incurable oesophageal cancer, significantly reducing the overall duration of treatment, while providing symptom response with an acceptable toxicity profile. A phase I/II accelerated fractionation study was conducted to evaluate the efficacy and toxicity of this approach. MATERIALS AND METHODS: Patients with incurable oesophageal cancer, symptomatic with dysphagia, Eastern Cooperative Oncology Group performance statusor=6 h apart), 5 days a week, over 2 weeks. RESULTS: Of the 39 evaluable patients, the dysphagia response rate was 69% (27/39) with a median response duration of 5.5 months. The median time to response was 4 weeks. Twenty-eight per cent (11/39) of patients had transient worsening in their dysphagia scores. Acute toxicity (weeks 1-8) occurred in 41% (16/39) of patients. An improvement in global quality of life by week 8 was seen in 42% of patients. There were no late neurological sequelae. The median overall survival was 8 (range 1.7-58+) months. CONCLUSION: The ideal palliative regimen should be relatively short, with minimal toxicity, while offering a favourable response profile. Accelerated fractionation fulfils these criteria and is a suitable treatment alternative for the palliation of dysphagia, especially if the goal is to deliver a higher total biological dose within a shorter (2 week) period of time.

Comparison of histologic grade between initial and follow-up biopsy in untreated, low to intermediate grade, localized prostate cancer.

OBJECTIVE: To examine the change of histologic grade of untreated, low to intermediate grade, clinically localized prostate cancer over time on repeat prostate biopsy. METHODS AND MATERIALS: In a prospective single-arm cohort study, patients were managed with observation alone unless they met pre-defined criteria of disease progression (PSA, clinical or histologic progression). Sixty-seven (54%) of a total of 123 eligible patients underwent follow-up prostate biopsy. Median time to the follow-up biopsy was 22 months (range: 7-60). RESULTS: On the follow-up biopsy, Gleason score was unchanged in 20 patients (30%), upgraded in 19 (28%), and downgraded in 27 (40%). Twenty-one (31%) had no malignancy on the follow-up biopsy. Sixteen (37%) of 43 patients with < or = 2 positive cores on the initial biopsy had negative follow-up biopsy, while only 2 (11%) out of 18 with > or = 3 positive cores on the initial biopsy did. Five (7%) patients were upgraded to Gleason score 8. There was no correlation between the extent of grade change and baseline variables (age, clinical stage, and initial PSA) as well as PSA doubling time. CONCLUSIONS: There was no consistent histologic upgrade on the follow-up biopsy at a median of 22 months in untreated, low to intermediate grade, clinically localized prostate cancer.

Is there a progression of histologic grade from radical prostatectomy to local recurrence in patients with clinically isolated local recurrence following surgery?

OBJECTIVE: To evaluate whether there is any histologic progression from radical prostatectomy (RP) to local recurrence in patients with clinically isolated local recurrence following RP. METHODS AND MATERIALS: A total of 43 patients with clinically isolated, biopsy proven, local recurrence following RP were retrospectively analyzed with respect to the change in Gleason score (GS) from RP to local recurrence. Central pathology review was undertaken for both RP and local recurrence biopsy specimens. The changes in primary and secondary Gleason grade (GG), and any potential correlation between the extent of GS change and other variables were also examined. RESULTS: Median age at the time of local recurrence was 67 years (range: 55-78). Median interval between RP and local recurrence was 3.6 years (range: 0.3-17.7). Eight had a short course (<3 months) of hormone therapy prior to RP. Initial GS of RP specimens was 5, 6, 7, 8, and 9 in 1, 3, 29, 1, and 9 patients, respectively. At the time of local recurrence, GS was upgraded in 13, unchanged in 23, and downgraded in 7. The extent of GS change was correlated with the interval between RP and local recurrence, but not with pathological T stage or age. CONCLUSION: There was no statistically significant change in GS from RP to local recurrence, although there was a trend toward a higher GS at the time of local recurrence. The extent of GS change was associated positively with the elapsed time to local recurrence.

Are serial bone scans useful for the follow-up of clinically localized, low to intermediate grade prostate cancer managed with watchful observation alone?

OBJECTIVE: To assess the predictive value of serial bone scans as a surveillance tool for bone metastasis in men with clinically localized prostate cancer and managed with watchful observation. PATIENTS AND METHODS: A prospective single-arm study was conducted to assess the feasibility of a watchful observation protocol with selective delayed intervention for patients with clinically localized prostate cancer, i.e. T1b-T2bN0M0, a Gleason score of 15 ng/mL the patient underwent bone scintigraphy every year. RESULTS: In all, 244 eligible patients were enrolled into the study. With a median follow-up of 30 months, 449 bone scans were taken (150 at baseline and 299 in follow-up evaluations); all 299 follow-up scans were negative for bone metastasis. Hence, the true rate of positive follow-up bone scans was estimated to be 0-1.0% (95% confidence). In all, 171 patients had at least one follow-up bone scan; of these, the number (%) of patients who had 1, 2, 3, 4 and >or= 5 follow-up scans was 89 (52), 53 (31), 17 (10), eight (4.7) and four (2.3), respectively. The PSA levels (ng/mL) corresponding to all follow-up bone scans were: 214 scans at PSA < 10, 61 at 10-14.9, 18 at 15-19.9 and six at >or= 20 (range 20.2-24.9). The probability of a negative bone scan was estimated to be 88-100% (95% confidence interval) when a PSA threshold of 15 ng/mL was used. CONCLUSION: The probability of positive findings in serial bone scans in untreated, localized, low to intermediate grade prostate cancer was low when the follow-up PSA level remained < 15 ng/mL. Avoiding bone scans in this group of patients would translate into a significant cost saving and reduction in their psychological and physical burden. As for those with a follow-up PSA of> 15 ng/mL, the role of serial bone scintigraphy remains undefined, as a longer follow-up and a larger sample are needed.

Urodynamic findings 3 months after radiotherapy in patients treated with conformal external beam radiotherapy for prostate carcinoma.

OBJECTIVE: To quantify the effect of radiotherapy (RT) on urodynamic function 3 months after RT in patients with prostate cancer undergoing definitive external beam RT. PATIENTS AND METHODS: Seventeen patients with clinically localized prostate cancer were accrued into a single-arm prospective study. Sixteen of the patients completed a scheduled multichannel video-urodynamic study at baseline and again 3 months after RT; the urodynamic variables were then compared to assess the nature and extent of urodynamic change caused by RT. Correlations were assessed between these quantitative changes and those in self-assessed qualitative urinary function measured by International Prostate Symptom Score (IPSS), Quality of Life assessment index (QoL) and urinary functional enquiry. RESULTS: There were significant changes detected by the urodynamic study 3 months after RT in bladder volume at capacity (mean decrease 70 mL) and bladder volume at first sensation when supine (mean decrease 85 mL), and a lower postvoid residual volume (mean 50 mL). There was no significant change in the remaining urodynamic variables (including maximum flow rate and voided volume), nor in bladder compliance, bladder instability or bladder outlet obstruction. The self-assessed qualitative urological function measured by the IPSS, QoL and median urinary frequency/24 h showed no significant change after RT. CONCLUSIONS: This is the first quantitative study to prospectively evaluate the effect of RT on urodynamics in patients with prostate cancer. Only a few urodynamic variables changed significantly 3 months after RT, while most, including self-assessed qualitative urinary function, did not. This finding corresponds well with the notion that most patients tolerate RT well and that acute RT-induced urinary symptoms resolve successfully, with the return of lower urinary tract function to baseline levels by 3 months after RT.

PSA doubling time of prostate carcinoma managed with watchful observation alone.

PURPOSE: To study prostate-specific antigen (PSA) doubling time of untreated, favorable grade, prostate carcinoma. METHODS AND MATERIALS: A prospective single-arm cohort study has been in progress to assess the feasibility of a watchful observation protocol with selective delayed intervention using clinical, histologic, or PSA progression as treatment indication in untreated, localized, favorable grade prostate adenocarcinoma (T1b-T2bN0 M0, Gleason Score < or = 7, and PSA < or = 15 ng/mL). Patients are conservatively managed with watchful observation alone, as long as they do not meet the arbitrarily defined disease progression criteria. Patients are followed regularly and undergo blood tests including PSA at each visit. PSA doubling time (Td) is estimated from a linear regression of ln(PSA) on time, assuming a simple exponential growth model. RESULTS: As of March 2000, 134 patients have been on the study for a minimum of 12 months (median, 24; range, 12-52) and have a median frequency of PSA measurement of 7 times (range, 3-15). Median age is 70 years. Median PSA at enrollment is 6.3 (range, 0.5-14.6). The distribution of Td is as follows: <2 years, 19 patients; 2-5 years, 46; 5-10 years, 25; 10-20 years, 11; 20-50 years, 6; > 50 years, 27. The median Td is 5.1 years. In 44 patients (33%), Td is greater than 10 years. There was no correlation between Td and patient age, clinical T stage, Gleason score, or initial PSA level. CONCLUSION: Td of untreated prostate cancer varies widely. In our cohort, 33% have Td > 10 years. Td may be a useful tool to guide treatment intervention for patients managed conservatively with watchful observation alone.

The role of serial transrectal ultrasonography in a 'watchful waiting' protocol for men with localized prostate cancer.

OBJECTIVE: To determine the value of serial 6-monthly transrectal ultrasonography (TRUS) in a cohort of men with localized prostate cancer who consented to a programme of watchful waiting with selective delayed intervention. PATIENTS AND METHODS: Since November 1995, 180 men were accrued into an ongoing prospective study of watchful waiting with selective delayed intervention; 174 patients enrolled before 31 December 1999 comprised the cohort for the present study. The prospectively collected clinical data, including the TRUS reports, were reviewed systematically. Twenty-eight men met the arbitrarily predefined criteria of disease progression and required definitive treatment. The TRUS findings were scored as being consistent with the clinical scenario (i.e. clinical, biochemical or histological progression) if they reported a new or enlarging hypoechoic peripheral zone lesion, or a > or = 30% increase in overall prostate volume at the time of progression. In 136 men who had undergone two or more serial TRUS examinations the relationships between the rate of change of prostate-specific antigen (PSA) and changes in both gland volume and the number of hypoechoic lesions were also examined. RESULTS: The group of 28 men who progressed to require radical intervention underwent 83 TRUS examinations (median number per patient, three). Two men underwent TRUS only once at baseline because of progression within 6 months. Of these 28 men, only seven had changes on TRUS that were regarded as being consistent with progression; all seven consisted of the growth of an existing nodule or the appearance of a new nodule. In only one case was this accompanied by an increase of > or = 30% in gland volume. In the 136 men who underwent two or more serial TRUS examinations (median three, maximum nine), there was no correlation between the rate of change of PSA and changes in either gland volume or the number of peripheral zone hypoechoic lesions. CONCLUSION: The use of serial TRUS in men with known but untreated prostate cancer is of limited value as a determinant of disease progression.

Coronary spasm and cardiac arrest from carcinoid crisis during laser bronchoscopy.

Bronchoscopic manipulation of an endobronchial carcinoid can precipitate a carcinoid crisis. Coronary artery spasm is an uncommon manifestation of carcinoid crisis, and has never been reported as a complication of flexible bronchoscopy. We report a case of a 10-year-old girl who developed coronary artery spasm and cardiac arrest during neodymiumyttrium aluminum garnet (Nd-YAG) laser photoresection of an endobronchial carcinoid. Recognition of this unusual presentation of a carcinoid crisis is important as the treatment approach differs from standard resuscitation protocols.

Reduced expression of the cell cycle inhibitor p27Kip1 in non-small cell lung carcinoma: a prognostic factor independent of Ras.

Levels of p27 have been found to have independent prognostic significance in a variety of tumors including breast, colon, prostate, ovary, and gastric carcinomas. We investigated p27 levels and determined ras mutational status in 136 non-small cell lung cancers. We found reduced levels of p27 in 86% of cases and showed a statistically significant inverse correlation between p27 levels and tumor grade. ras mutations were found exclusively in adenocarcinomas and showed no relationship to p27 levels. Clinical data on a subset of the patients studied indicated that all 16 patients who died of disease and 21 of 22 patients who relapsed had low p27 levels, whereas all patients with high p27 levels were alive at last follow up. These findings suggest that alteration in p27 levels plays an important role in lung tumor progression and that p27 levels may have independent prognostic significance in non-small cell lung cancer.

Loss of cyclin-dependent kinase inhibitor p27Kip1 is a novel prognostic factor in localized human prostate adenocarcinoma.

p27Kip1 is a cyclin-dependent kinase inhibitor that negatively regulates cell proliferation by mediating cell cycle arrest in G1. This study was undertaken to assess the prognostic value of p27Kip1 in localized human prostate cancer. Archival material from 113 radical prostatectomy specimens obtained between 1985 and 1993 was stained immunohistochemically for p27Kip1 protein using a commercially available antibody. Patient charts were reviewed for preoperative serum prostate-specific antigen, clinical and pathological staging, Gleason tumor grade, time to biochemical and clinical recurrence, and survival. Strong p27Kip1 staining was uniformly seen in benign prostatic epithelial components in all tumor sections. p27Kip1 staining was reduced in most prostate cancers and was variable in prostatic intraepithelial neoplasia. Decreased p27Kip1 staining (<25% of nuclei stained positive for p27Kip1) correlated with seminal vesicle involvement (P = 0.0032) and with higher Gleason grade (P = 0.0114). On univariate analysis, low p27Kip1 predicted an increased risk of treatment failure in the node-negative cohort (P = 0.0037) and in the subset who did not receive neoadjuvant hormonal therapy (P = 0.049). Low p27Kip1 expression was an independent predictor of treatment failure on multivariate analysis of lymph node negative prostate cancers following radical retropubic prostatectomy (n = 102; P = 0.047). Seminal vesicle involvement (P = 0.034) and positive surgical margins (P = 0.047) were also independent prognostic factors for disease recurrence. In patients who received preoperative neoadjuvant hormonal therapy, low p27Kip1 in the pathological specimen was an even stronger predictor of outcome than it was in the entire group (n = 23, P = 0.015).

P-glycoprotein expression: critical determinant in the response to osteosarcoma chemotherapy.

BACKGROUND: Fewer than 20% of patients with bone cancer who are treated with surgery alone are cured. Even with the best current treatment, surgery combined with chemotherapy, only 60%-80% of patients with nonmetastatic bone cancer and 10% of patients with metastatic bone cancer are cured. Thus far, the reason for treatment failure in the nonresponding subset has not been identified. It has been hypothesized that P-glycoprotein, which confers multidrug resistance, might be the cause. We sought to determine whether the expression of P-glycoprotein is associated with poor treatment outcome in osteosarcoma. METHODS: In a retrospective study, we correlated P-glycoprotein expression with the outcome of conventional chemotherapy in 62 consecutive, clinically staged patients diagnosed as having osteosarcoma between 1980 and 1989. RESULTS: P-glycoprotein was overexpressed in 27 patients but not in another 34 patients, and expression was ambiguous in the sample from one patient. At a median follow-up of 8.9 years, the 34 patients whose tumors did not express P-glycoprotein had significantly better relapse-free rates than the 27 subjects whose tumors expressed the protein (87% versus 0%; P<.00001) and had improved survival rates (94% versus 35%; P<.00001). Among the 46 patients who received chemotherapy before surgery, the 23 whose tumors were negative for P-glycoprotein showed significantly better long-term outcomes (P<.00002), although differences in tumor necrosis in response to therapy were only of borderline significance (P = .057). CONCLUSIONS: P-glycoprotein expression does correlate with treatment failure in patients with osteosarcoma. This correlation raises the possibility that inhibiting the action of P-glycoprotein as part of therapy for this disease would improve outcome.

An individual patient-based meta-analysis of tamoxifen versus ovarian ablation as first line endocrine therapy for premenopausal women with metastatic breast cancer.

We performed a meta-analysis of randomized trials comparing tamoxifen to ovarian ablation carried out either by surgery or irradiation as first-line hormonal therapy for pre-menopausal women with metastatic breast cancer. Patients in all trials included were required to have measurable disease and to be currently menstruating or within 1 year of cessation of menses, and to have estrogen receptor (ER) positive or unknown disease (ER negative women were admitted to one of the studies). Individual patient data were obtained from the four studies identified and the results updated to June 1992. A total of 220 eligible patients were enrolled in the four trials. There was no difference in overall response rate between tamoxifen and oophorectomy across the four trials (p = 0.94, Mantel-Haenszel test). The odds reduction for progression was 14% +/- 12% and for mortality 6% +/- 13% in favour of tamoxifen, results which were not statistically significant (p = 0.32 and 0.72, respectively). Although the design of all four studies included a cross-over to the other therapy, only 54/111 patients receiving ovarian ablation and 34/109 patients receiving tamoxifen as primary therapy actually crossed over to the other arm at the time of disease progression. Response to initial treatment with tamoxifen was predictive of subsequent response to ovarian ablation (p < 0.05), and response to initial therapy with ovarian ablation was predictive of subsequent response to tamoxifen (p < 0.05). Support curves based on log-likelihood ratios revealed that this meta-analysis provides moderate evidence rejecting a 14% advantage for ovarian ablation compared to tamoxifen in terms of odds of disease progression. A 25% advantage for ovarian ablation with respect to odds of death is also rejected with moderate evidence. We conclude that the efficacy of tamoxifen appears to be similar to that of ovarian ablation by surgery or irradiation as first-line therapy for premenopausal, ER positive metastatic breast cancer, and is unlikely to be substantially inferior.

A randomized crossover trial of tamoxifen versus ovarian ablation for metastatic breast cancer in premenopausal women: a report of the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) trial MA.1.

We concluded a randomized crossover trial comparing tamoxifen 40 mg daily with ovarian ablation for treatment of metastatic breast cancer in premenopausal women. Objective responses (complete response (CR) plus partial response (PR)) were observed in 5/20 patients treated initially with tamoxifen and in 3/19 patients initially treated with ovarian ablation (p = 0.69). Seven additional patients were stable (SD) on tamoxifen while five additional patients were stable after ovarian ablation, for CR + PR + SD rates of 12/20 (60%) for tamoxifen and 8/19 (42%) for ovarian ablation (p = 0.34). Median time to disease progression was 184 days for tamoxifen and 126 days for ovarian ablation (p = 0.40, logrank test, odds ratio for progression 0.71). Overall survival times were also similar: a median of 2.35 years for tamoxifen and 2.46 years for ovarian ablation (p = 0.98, logrank test, odds ratio for death 1.07). Side effects from tamoxifen included hot flashes and menstrual abnormalities. With one exception, these toxicities were not sufficient to require dose reduction. In this small study, tamoxifen was associated with similar response rates, response durations, and survival times to those observed with ovarian ablation.

MYCN protein expression as a predictor of neuroblastoma prognosis.

About half of nonlocalized neuroblastomas have MYCN gene amplification and usually progress rapidly, but the half without such amplification also do poorly, albeit progressing more slowly. We hypothesize that overexpression of MYCN protein can occur without gene amplification and that this expression reliably predicts the prognosis of neuroblastoma. To determine whether MYCN expression correlated with outcome, we assayed MYCN protein immunohistochemically in 180 archival pretreatment and posttreatment samples and stratified the 57 conventionally treated stage IVS, III, and IV patients by these conventional prognostic factors: stage, age, serum ferritin, Shimada histology, urinary catecholamine ratio, and MYCN gene status. At a median follow-up of >/=6.8 years, we found in patients with known MYCN gene status that the 23 of 37 without gene amplification fared no better than the 14 of 37 with gene amplification (P = 0.35 and 0.21, comparing relapse-free and survival rates). Conversely, in patients without MYCN gene amplification, 9 of 23 were found to overexpress MYCN protein pretreatment, and they did worse than the 14 of 23 without detectable MYCN protein (P = 0.0016 and 0.022, comparing relapse-free and survival rates). Furthermore, MYCN protein expression was prognostic without (P = 0.00001) and with (P = 0.0007) stratifying all 57 patients by MYCN gene status, each conventional prognostic factor (P ranging from 0.00001-0.013), or simultaneously by the two most important factors, stage and age (P = 0.00076). We conclude that overexpression of MYCN protein without gene amplification correlated significantly with the clinical behavior of neuroblastoma and predicted outcome independently of other prognostic factors. This strongly supports the hypothesis that expression of the MYCN oncogene is critical for progression of neuroblastoma.

Survey of consecutive prostate cancer patients attending the Toronto Sunnybrook Regional Cancer Centre (TSRCC).

OBJECTIVE: To survey a sample of consecutive new prostate cancer patients attending the multidisciplinary clinic at the Toronto Sunnybrook Regional Cancer Centre (TSRCC). To assess the reason for their initial investigation, what treatment they received, the reason for their referral, their opinion and expectations prior to their referral to the TSRCC. To compare their choice of treatment with the reason for their referral, and the treatment recommended prior to their visit to the TSRCC.

Chemotherapy with focal therapy can cure intraocular retinoblastoma without radiotherapy.

BACKGROUND: External beam radiotherapy is standard treatment for medium and large, or visually threatening, intraocular retinoblastoma but markedly increases the risk of cosmetic deformities and second malignant neoplasms in children with germline RB1 mutations. Large tumors and those with vitreous seeds do poorly despite radiotherapy. Chemotherapy traditionally is ineffective for intraocular retinoblastoma, perhaps because many retinoblastomas overexpress the multidrug resistance protein, P-glycoprotein. OBJECTIVE: To avoid radiotherapy in the management of intraocular retinoblastoma by using chemotherapy and focal therapy. INTERVENTIONS: We shrank retinoblastomas in 40 eyes of 31 patients that conventionally should be enucleated or receive radiotherapy by using chemotherapy (ie, vincristine-teniposide, 8 eyes; additional carboplatin, 32 eyes) combined with the administration of cyclosporine, a known multidrug-resistance-reversal agent. We then consolidated these responses to chemotherapy by subsequent 532- and 1064-nm laser therapy and cryotherapy. RESULTS: At the median follow-up of 2 2/3 [corrected] years (range, 1/10-4 3/4 years), the results of treatment were excellent. The actuarial relapse-free rate was 89% in patients not previously treated (91% for 28 eyes) and 67% in patients treated after relapse from previous therapy (70% for 12 eyes). For the eyes with the worst prognosis (ie, vitreous seeds), the relapse-free rate was 88%, better than previously reported. Cyclosporine is nontoxic and did not enhance the expected toxic effects of chemotherapy. Most eyes required laser therapy, cryotherapy, or both for consolidation of tumor control. CONCLUSIONS: This pilot study suggests that most retinoblastomas are curable by combining chemotherapy with cyclosporine therapy, laser therapy, and cryotherapy, without requiring external beam radiotherapy. We propose a randomized trial to clarify the role of cyclosporine.

Effect of cranial surgery and brain tumor size on emergence from anesthesia.

BACKGROUND: Knowing which neurosurgical patients are at risk for delayed awakening may lead to better utilization of intensive care resources and avoid the risk and cost of pharmacologic reversal and diagnostic tests. METHODS: The authors compared anesthetic emergence from complex spinal surgery (spine; n = 47) with that from craniotomy for supratentorial nonfrontal (n = 22), frontal (n = 34), or posterior fossa tumor (n = 28). A further comparison involved patients with small versus large (diameter > 30 mm, mass effect) tumors. The standardized anesthetic regimen consisted of induction with 2-4 mg/kg-1 thiopental and 1-2 micrograms/kg-1 sufentanil, followed by maintenance with nitrous oxide, 0.2-0.5 micrograms.kg-1.h-1 sufentanil and < or = 0.5% isoflurane. Sufentanil administration was terminated on dural or spinal muscle closure, isoflurane during skin closure, and nitrous oxide during dressing application. After discontinuing nitrous oxide, a minineurologic examination was performed every 15 min for 1 h, then hourly for 4 h and at 24 h. RESULTS: Craniotomy patients performed less well than spinal surgery patients on the minineurologic examination 15 and 30 min after discontinuing nitrous oxide. At 15 min, fewer patients with large (vs. small) tumors were oriented to time (58% vs. 87%; P < 0.01) or place (67% vs. 90%; P < 0.01). Forty-two percent of patients with large tumors still had an abnormal minineurologic examination score versus 15% of patients with small tumors. At 30 min, these values were 28% and 8%, respectively (P < 0.05). Seventy-one percent of patients with large tumors were oriented to time compared to 97% for small lesions (P < 0.01). Emergence from anesthesia was similar for spinal surgery patients and patients with small brain tumors. CONCLUSION: Patients undergoing craniotomy for large intracranial mass lesions awaken more slowly than patients after spinal surgery or craniotomy for small brain tumor.