Resection of brain metastases previously treated with stereotactic radiosurgery

OBJECT: To date, no report has been published on outcomes of patients undergoing resection for brain metastases who were previously treated with stereotactic radiosurgery (SRS). Consequently, the authors reviewed their institutional experience with this clinical scenario to assess the efficacy of surgical intervention. METHODS: Sixty-one patients (each harboring three or fewer brain lesions), who were treated at a single institution between June 1993 and August 2002 were identified. Patient charts and their neuroimaging and pathological reports were retrospectively reviewed to determine overall survival rates, surgical complications, and recurrence rates. A univariate analysis revealed that patient preoperative recursive partitioning analysis (RPA) classification, primary disease status, preoperative Karnofsky Performance Scale score, type of focal treatment undergone for nonindex lesions, and major postoperative surgical complications were factors that significantly affected survival (p < or = 0.05). In contrast, only the RPA class and focal (conventional surgery or SRS) treatment of nonindex lesions significantly (or nearly significantly) affected survival in the multivariate analysis. Major neurological complications occurred in only 2% of patients. The median time to distant recurrence after resection was 8.4 months; that to local recurrence was not reached. The overall median survival time was 11.1 months, with 25% of patients surviving 2 or more years. Conventional surgery facilitated tapering of steroid administration. Conclusions. The complication, morbidity, survival, and recurrence rates are consistent with those seen after conventional surgery for recurrent brain metastases. Our results indicate that in selected patients with a favorable RPA class in whom nonindex lesions are treated with focal modalities, surgery can provide long-term control of SRS-treated lesions and positively affect overall survival.     

Actinomycosis esophagitis in a patient with persistent dysphagia

Many causes of esophagitis exist in immunocompromised patients. Uncommon pathogens must be considered to facilitate timely and appropriate therapy. A limited number of cases of esophageal actinomycosis have been reported. This report describes an unusual case of esophageal actinomycosis in a patient with persistent dysphagia. The broad differential may have delayed definitive diagnosis in the case study patient. Biopsy and culture are essential for accurate diagnosis. Although actinomycosis is a rare disease, it should be included in the differential diagnosis of patients presenting with oral or esophageal complaints. It may also be considered as an opportunistic infection in immunocompromised patients. The treatment of choice is parenteral penicillin G, 18 to 24 million units for 2 to 6 weeks followed by oral therapy for 6-12 months.     

Cricothyroid approximation and subluxation in 21 male-to-female transsexuals

OBJECTIVES: To evaluate the medium-term outcome of cricothyroid approximation and subluxation (CTAS) with postoperative speech therapy for pitch elevation in male-to-female transsexuals. STUDY DESIGN: Retrospective study of male-to-female transsexuals who underwent pitch-raising surgery between November 1996 and August 2001. METHODS: Twenty-one male-to-female transsexuals opted for surgical feminization of their voices after inadequate improvements with speech therapy alone. Electrolaryngographic measurements were obtained by a single speech therapist of modal fundamental frequencies and the percentage of irregularities before, at 2 weeks, and 6 months after surgery. All 21 patients underwent CTAS, and 20 underwent simultaneous cosmetic thyroid chondroplasty by a single surgeon. RESULTS: Electrolaryngographic results 2 weeks after surgery showed an average postoperative gain in modal frequency of free speech of 71.05 Hz (95% confidence interval [CI]: 42.9-99.2, P < .001). There was a concomitant average rise in irregularities of 9.9% (95% CI 0.7-18.5, P = .03). At median follow-up of 6 months after six sessions of speech therapy (n = 15), there was a decrease in irregularities to preoperative levels. The overall gain at 6 months in modal frequency of free speech was 56.9 Hz (95% CI 38.3-75.4, P < .001). Smoking and age did not predict a worse outcome. CONCLUSIONS: Cricothyroid approximation effectively raises pitch in male-to-female transsexuals. There is a concomitant rise in voice irregularities that is effectively addressed by speech therapy.     

Cystic glioblastoma multiforme: survival outcomes in 22 cases

OBJECT: The goal of this study was to determine whether the presence of a large tumor cyst was associated with improved outcome in patients undergoing surgery for newly diagnosed glioblastomas multiforme (GBMs) by comparing these patients with a matched cohort of patients with noncystic GBMs in clinical features, tumor imaging characteristics, survival, and time to tumor recurrence after surgery. METHODS: A retrospective analysis was conducted in 22 patients by using imaging information and chart reviews of operative reports of GBMs with large cysts (> or = 50% of tumor volume) at The University of Texas M. D. Anderson Cancer Center between 1993 and 2002. Clinical and neurosurgical outcomes and recurrence rates were studied. A statistical comparison was made with a matching cohort of 22 patients with noncystic GBMs. No significant differences in clinical variables were found between the cohort with cystic GBMs and the matched cohort with noncystic GBMs. To avoid bias in preoperative assessment of tumor volume, the tumor burden was compared in patients whose tumors had cysts (excluding the cystic mass) and in patients whose tumors did not contain cysts. There was no statistically significant difference between the two groups (p = 0.8). In patients with cystic GBMs the median survival time after surgery was 18.2 months (95% confidence interval [CI] 11.9-24.5 months) and at 2 years 43% of the patients were still alive. In comparison, in patients with noncystic GBMs, the median survival time was 14.3 months (95% CI 12.1-16.4 months) and only 16% of patients were alive at 2 years. The median time to tumor recurrence was 7.6 months (95% CI 0.01-18 months) in patients harboring cystic GBMs and 4.2 months (95% CI 1.8-6.6 months) in the matched cohort (log-rank test, p = 0.04). In the cystic GBM group, no recurrence was observed in 53% of patients at 6 months, 45% at 1 year, and 38% at 2 years after surgery, whereas the corresponding numbers for the noncystic group were 36, 14, and 9%, respectively. CONCLUSIONS: The results indicate that patients harboring a GBM that contains a large cyst survive longer and have a longer time to recurrence than those who lack such a cyst. This is the first such observation in the literature.     

The surgical bed after BCNU polymer wafer placement for recurrent glioma: serial assessment on CT and MR imaging

OBJECTIVE: The objective of our study was to describe the CT and MR imaging appearances of the surgical bed in the brains of patients receiving biodegradable polymers impregnated with N, N'1, 3-Bis-(2-chloroethyl)-N-nitrosourea (BCNU) for recurrent glioma and to determine whether patients receiving placebos could be differentiated from those receiving BCNU based on the pattern and growth kinetics of tumor recurrence. MATERIALS AND METHODS: The CT and MR images of 20 patients who underwent surgery for resection of recurrent high-grade gliomas and placement of intratumoral wafers (11 received BCNU polymer wafers, nine received control wafers) were analyzed for wafer appearance, volume of gas in the tumor bed, and volume of enhancement on serial scans. RESULTS: Wafers appeared as linear hyperdense structures on CT and as linear low-signal-intensity structures on MR imaging and caused no significant enhancement. In the BCNU polymer group, gas volume was 4.0 +/- 3.4 cm(3) (mean +/- SD), whereas gas volume was 1.6 +/- 3.0 cm(3) for the placebo group (Mann-Whitney test, p = 0.03). A trend toward linear rather than exponential recurrent tumor growth was identified for the BCNU polymer group but not for the placebo group. CONCLUSION: BCNU polymer wafers have a specific appearance on CT and MR imaging with which radiologists should be familiar: gas in the surgical bed is an expected transient finding, and tumor regrowth in patients receiving BCNU polymer wafers appeared to occur at a slower rate than in those receiving the placebo.     

Oxygenation using tidal volume breathing after maximal exhalation

We compared, in volunteers, the oxygenation achieved by tidal volume breathing (TVB) over a 3-min period after maximal exhalation with that achieved by TVB alone. Twenty-three healthy volunteers underwent the two breathing techniques in a randomized order. A circle absorber system with an oxygen flow of 10 L/min was used. The end-expiratory oxygen concentration (EEO(2)) was monitored at 15-s intervals up to 3 min. TVB after maximal exhalation produced EEO(2) values of 68% +/- 5%, 75% +/- 5%, and 79% +/- 4% at 30, 45, and 60 s, respectively, which were significantly larger (P < 0.05) than the corresponding values obtained with TVB alone (58% +/- 5%, 66% +/- 6%, and 71% +/- 5%, respectively). In both techniques, the EEO(2) increased exponentially, with time constants of 35 s during TVB after maximal exhalation versus 58 s during TVB without prior maximal exhalation. In conclusion, maximal exhalation before TVB can hasten preoxygenation by decreasing the nitrogen content of the functional residual capacity, with a consequent increase of EEO(2) to approximately 70% in 30 s and 80% in 60 s. IMPLICATIONS: Oxygenation by using maximal exhalation before tidal volume breathing produced a significantly faster increase in end-expiratory oxygen concentration than oxygenation with tidal volume breathing alone.     

Quinacrine induces cytochrome c-dependent apoptotic signaling in human cervical carcinoma cells

Quinacrine (QU), a phospholipase-A2 (PLA-2) inhibitor has been used clinically as a chemotherapeutic adjuvant. To understand the mechanisms leading to its chemotherapeutic effect, we have investigated QU-induced apoptotic signaling pathways in human cervical squamous carcinoma HeLa cells. In this study, we found that QU induced cytochrome c-dependent apoptotic signaling. The release of pro-apoptotic cytochrome c was QU concentration- and time-dependent, and preceded activation of caspase-9 and -3. Flow cytometric FACScan analysis using fluorescence intensities of DiOC6 demonstrated that QU-induced cytochrome c release was independent of mitochondrial permeability transition (MPT), since the concentrations of QU that induced cytochrome c release did not alter mitochondrial membrane potential (delta pai(m)). Moreover, kinetic analysis of caspase activities showed that cytochrome c release led to the activation of caspase-9 and downstream death effector, caspase-3. Caspase-3 inhibitor (Ac-DEVD-CHO) partially blocked QU-induced apoptosis, suggesting the importance of caspase-3 in this apoptotic signaling mechanism. Supplementation with arachidonic acid (AA) sustained caspase-3 activation induced by QU. Using inhibitors against cellular arachidonate metabolism of lipooxygenase (Nordihydroxyguaiaretic Acid, NDGA) and cyclooxygenase (5,8,11,14-Eicosatetraynoic Acid, ETYA) demonstrated that QU-induced apoptotic signaling may be dependent on its role as a PLA-2 inhibitor. Interestingly, NDGA attenuated QU-induced cytochrome c release, caspase activity as well as apoptotic cell death. The blockade of cytochrome c release by NDGA was much more effective than that attained with cyclosporin A (CsA), a MPT inhibitor. ETYA was not effective in blocking cytochrome c release, except under very high concentrations. Caspase inhibitor z-VAD blocked the release of cytochrome c suggesting that this signaling event is caspase dependent, and caspase-8 activation may be upstream of the mitochondrial events. In summary, we report that QU induced cytochrome c-dependent apoptotic signaling cascade, which may be dependent on its role as a PLA-2 inhibitor. This apoptotic mechanism induced by QU may contribute to its known chemotherapeutic effects.