Dexamethasone-induced abolition of the inflammatory response in an experimental glioma model: a flow cytometry study.

OBJECT: Commonly used for management of cerebral edema in patients with brain tumors, steroid medications also have immunosuppressive functions. To characterize the effects of steroids on the central nervous system's response to tumors more clearly, flow cytometry was used to quantify the extent of inflammatory cell infiltration in an immunogenic rat glioma model. METHODS: Freshly prepared 11-day-old intracranial C6 tumors that had been excised from dexamethasone-treated and untreated rats were labeled ex vivo with monoclonal antibodies against CD 11b/c, CD45, and CD8a antigens. The extent of microglia (CD11b/c-highly positive, CD45-slightly positive cell), macrophage (CD11b/c-highly positive, CD45-highly positive cell), lymphocyte (CD11b/c-negative, CD45-highly positive cell), and cytotoxic T-cell (CD8a-positive cell) infiltration into each rat's tumor, tumor periphery, and contralateral tumor-free hemisphere was analyzed using flow cytometry. Microglia and lymphocytes constituted a significant component of infiltrating cells in this model, comprising 23 +/- 3% and 33 +/- 5% of viable cells, respectively. Macrophages, on the other hand, accounted for only 9 +/- 1% of infiltrating cells. Treatment of rats with a 7-day course of low-dose dexamethasone (0.1 mg/kg/day) resulted in a greater than 50% inhibition of microglia (p = 0.03) and lymphocyte (p = 0.001) infiltration into tumors. Increasing the dexamethasone dose to 1 mg/kg/day further abolished lymphocyte infiltration (89% inhibition, p = 0.001) but had no additional inhibitory effect on microglia invasion. Macrophage infiltration of tumors was not inhibited at the dexamethasone doses used in this study (p = 0.42). CONCLUSIONS: Flow cytometry is a valuable technique for characterizing tumor-associated inflammatory cells in gliomas. Even at low doses, dexamethasone was found to inhibit significantly the infiltration of brain tumors by lymphocytes and microglia. These findings should be considered when experimental immunotherapeutic strategies are evaluated for clinical application.

Use of titanium mesh for reconstruction of large anterior cranial base defects.

The authors evaluated the role of titanium mesh used in combination with vascularized pericranium to provide rigid support during reconstruction of anterior skull base defects. Thirteen patients with large anterior skull base defects caused by tumor invasion or traumatic injury involving the cribriform plate, orbital roof, and planum sphenoidale were included in the study. The reconstruction technique involved placement of titanium mesh between two layers of continuous vascularized pericranium. Surgical glue and routine lumbar cerebrospinal fluid (CSF) drainage were not used in any patient. At a mean postoperative follow-up time of 22 months (range 8-39 months), none of the patients had developed infection or meningocele. Postoperative CSF rhinorrhea occurred in two patients with extensive dural defects, which resolved with temporary lumbar drainage. Use of titanium mesh and a two-layer vascularized pericranial graft is a safe, reproducible, and feasible method for reconstructing the anterior skull base. Patients with large dural defects may need temporary CSF diversion to avoid postoperative fistula formation.

Endoscopic-guided direct endonasal approach for pituitary surgery.

BACKGROUND: Submucosal dissection of the nasal septum is often performed as part of the transseptal approach to the sella. To evaluate whether this submucosal dissection is a necessary component of this operation, we compared the morbidity of a direct transmucosal endonasal approach to that of the transseptal approach in patients undergoing pituitary surgery. METHODS: Forty-one consecutive patients undergoing pituitary surgery from January 1996 to March 1999 were included in this study. The first 21 patients underwent the standard transseptal operation through either a sublabial or columellar incision. The latter 20 patients were operated on through an endoscopically guided, direct endonasal exposure, without any submucosal dissection of the nasal septum. The operative morbidity, the duration of surgery, and the length of hospitalization for each group were compared. RESULTS: The sphenoid sinus exposure obtained through the endonasal route was comparable with the transseptal approach and was adequate for resection of most pituitary tumors. Although the morbidity of the two approaches was similar, patients undergoing the endonasal operation had less postoperative facial pain. Furthermore, the endonasal approach significantly decreased the length of the operation (116 minutes vs. 161 minutes, p = 0.002) and the duration of hospitalization (3.6 vs. 5.1 days, p = 0.003) as compared with the transseptal route. CONCLUSIONS: Morbidity of the endonasal approach to the sphenoid sinus is comparable to that of a conventional transseptal approach. By eliminating the submucosal dissection, the endonasal approach reduces postoperative facial discomfort and decreases length of surgery and hospitalization.

Tumour cell dispersion by the ultrasonic aspirator during brain tumour resection.

Ultrasonic aspirators are commonly used to resect brain tumours because they allow safe, rapid and accurate removal of diseased tissue. Since ultrasonic aspirators generate a spray of aerosolized irrigating fluid around the instrument tip, we questioned whether this spray might contain viable tumours cells that could contribute to intraoperative spread of tumour fragments. To test this hypothesis, we collected the spray produced during the resection of nine brain tumours with an ultrasonic aspirator and semi-quantitatively analysed it for tumour presence. The aerosolized irrigation fluid was found to contain intact tumour cells or clumps of tumour cells in all nine instances, and there was a trend of increasing tumour cell dispersion with increasing ultrasonic aspiration times. Further examination is required to determine if this intraoperative dispersion of apparently viable tumour fragments contributes to local neoplasm recurrence.

A canine model of acute hindbrain ischemia and reperfusion.

Animal models of brain stem ischemia are needed for pathophysiological study and evaluation of treatment; few such models are available currently. A new canine model of hindbrain ischemia and reperfusion is introduced in this article. Through an anterior cervical approach, the basilar artery was surgically exposed in 18 dogs. The posterior communicating and superior cerebellar arteries were embolized with cyanoacrylate glue to isolate the posterior circulation from the anterior circulation. Reversible hindbrain ischemia was induced in 14 dogs by the temporary clipping of the vertebral and ventral spinal arteries for various periods (10-30 min), then the clips were removed and reperfusion was achieved for 5 hours. In all 14 dogs, the hindbrain ischemia was confirmed by the decreased perfusion pressure in the basilar artery (< 10 mm Hg), the diminished regional cerebral blood flow as measured with a laser Doppler flowmeter at the medulla oblongata (< 10 ml/100 g/min), the flattened brain stem auditory evoked potentials, and the increased leakage of Evans blue dye from tissue. These parameters did not change in the four control dogs. The changes in brain stem auditory evoked potentials were closely related to the length of ischemic interval; after 10 minutes of ischemia, reperfusion fully reversed the changes in brain stem auditory evoked potentials, but 20-minute and 30-minute ischemic intervals partially or totally depleted the brain stem auditory evoked potentials. Delayed postischemic hypoperfusion occurred in all five dogs that underwent the 30-minute ischemic interval. The early physiological changes in this model allowed us to estimate the severity of brain stem ischemia and the resulting damage.(ABSTRACT TRUNCATED AT 250 WORDS)