Therapy for patients with high grade astrocytoma using intraarterial chemotherapy and radiation therapy.

BACKGROUND: High grade astrocytomas account for approximately 40% of all primary brain tumors. The median survival is approximately 8-10 months for patients with glioblastoma multiforme and 36 months for patients with anaplastic astrocytoma. The results of systemic chemotherapy in the treatment of brain tumors have been reported to be less than satisfactory, mainly because of the blood-brain barrier impermeability for chemotherapeutic drugs. Intraarterial chemotherapy has been an attractive alternative with which to overcome this problem. METHODS: Eighty-three patients with high grade astrocytoma (glioblastoma multiforme [63 patients] and anaplastic astrocytoma--[20 patients]) were treated with intraarterial (intracarotid and/or intravertebral) chemotherapy and radiation therapy between 1987 and 1997. Patients received cisplatin, 60 mg/m2, and etoposide, 40 mg/m2. Radiation therapy was delivered either after completion of the chemotherapy or concomitantly with the chemotherapy. RESULTS: Thirty-four of 71 evaluable patients with high grade astrocytoma (48%) responded to the chemotherapy. The median survival for patients with glioblastoma multiforme who received chemotherapy prior to radiation therapy was 20 months versus 7 months for those patients who underwent concomitant chemotherapy/radiation therapy. Patients with anaplastic astrocytoma who received chemotherapy prior to radiation therapy had a median survival of 45 months compared with 12 months for patients who received concomitant chemotherapy/ radiation therapy. The toxicity profile has been reported to be mild and well tolerated. CONCLUSIONS: Intraarterial chemotherapy for patients with glioblastoma multiforme, delivered prior to radiation therapy, appears to result in a median survival three times longer than that achieved with concomitant chemotherapy/radiation therapy. In addition, patients appear to survive substantially longer than they do after radiation therapy with the addition of systemic chemotherapy. Side effects are reported to be acceptable.

Diffusion- and perfusion-weighted MR imaging of dural sinus thrombosis.

A patient with dural sinus thrombosis had progressively worsening symptoms and signs that resolved after intradural thrombolysis. Intradural sinus pressures were 54 mm Hg. Echo-planar MR imaging revealed complex abnormalities of diffusion and widespread delay in mean transit time that improved immediately after thrombolysis. This case suggests that diffusion- and perfusion-weighted imaging can provide valuable information noninvasively to help triage patients with dural sinus thrombosis between conservative and aggressive management.

Toxicities related to intraarterial infusion of cisplatin and etoposide in patients with brain tumors.

Chemotherapy for malignant brain tumors has a limited efficacy largely due to restricted blood-brain barrier permeability for chemotherapeutic drugs. Intraarterial chemotherapy (IAC) has the advantage of increased uptake during the first passage of the drugs through tumor capillaries. Initial IAC trials had less than satisfactory results due to unacceptable toxicities. Between 1987 and 1996, 173 patients with primary and metastatic brain tumors were treated with intraarterial (intracarotid and/or intravertebral) cisplatin and etoposide (VP-16). Out of these, 168 patients, who received a total of 438 cycles, were evaluated for the incidence of toxicities. Patients received either cisplatin at 40 mg/m2 and VP-16 at 20 mg/m2 or cisplatin at 60 mg/m2 and VP-16 at 40 mg/m2. Nausea and vomiting were the most common toxicities (42 patients, 14% of cycles). Arterial puncture was associated with a 1.6% incidence of groin hematomas (6 patients), and a 0.7% incidence of failure to canulate the carotid or vertebral arteries (3 patients). Neurologic toxicities included headache (1.4% of cycles, 5 patients), focal seizures (1.4% of cycles, 5 patients), transient confusion and urinary retention/incontinence (1.9% of cycles, 8 patients), and blurred vision (0.9% of cycles, 4 patients). We have not seen visual loss, strokes, major vessel dissection or thrombosis, or myelosuppression. Toxicity incidence was higher in patients with metastatic brain tumors than in those with primary brain tumors (34% versus 17%, p < 0.001). It was also higher in patients who had brain radiation therapy (RT) prior to IAC than in those who had RT concomitant with IAC (31% versus 19%, p = 0.05). No significant difference in toxicity incidence was noticed between patients who received RT concomitant with IAC and those who received RT after IAC (19% and 23% respectively, p = 0.08). Intracarotid chemotherapy given prior to RT resulted in 23 months of median survival for patients with glioblastoma multiforme. Intraarterial chemotherapy with cisplatin and VP-16 is a relatively safe treatment modality, especially in patients with primary brain tumors who have not received brain radiotherapy.

Acute internal jugular vein thrombosis associated with pseudoabscess of the retropharyngeal space.

We present four patients in whom evidence of edema or a pseudomass in the retropharyngeal space was found on CT scans obtained after thrombosis of the internal jugular vein. The clinical condition of one patient led to surgery, which documented the sterility of the retropharyngeal space despite the CT appearance of an inflammatory process. The CT findings, which are confusing initially, are found to be typical in retrospect.

A comparison of thrombolytic therapy with operative revascularization in the initial treatment of acute peripheral arterial ischemia.

PURPOSE: Despite the widespread use of intraarterial thrombolytic therapy for peripheral arterial occlusive disease, a randomized study comparing its efficacy with that of operative intervention has never been performed. This study evaluates the potential of intraarterial urokinase infusion to provide clinical benefits in patients with acute peripheral arterial occlusion. METHODS: Patients with limb-threatening ischemia of less than 7 days' duration were randomly assigned to intraarterial catheter-directed urokinase therapy or operative intervention. Anatomic lesions unmasked by thrombolysis were treated with balloon dilation or operation. The primary end points of the study were limb salvage and survival. RESULTS: A total of 57 patients were randomized to the thrombolytic therapy group, and 57 patients were randomized to the operative therapy group. Thrombolytic therapy resulted in dissolution of the occluding thrombus in 40 (70%) patients. Although the cumulative limb salvage rate was similar in the two treatment groups (82% at 12 months), the cumulative survival rate was significantly improved in patients randomized to the thrombolysis group (84% vs 58% at 12 months, p = 0.01). The mortality differences seemed to be primarily attributable to an increased frequency of in-hospital cardiopulmonary complications in the operative treatment group (49% vs 16%, p = 0.001). The benefits of thrombolysis were achieved without significant differences in the duration of hospitalization (median 11 days) and with only modest increases in hospital cost in the thrombolytic treatment arm (median $15,672 vs $12,253, p = 0.02). CONCLUSIONS: Intraarterial thrombolytic therapy was associated with a reduction in the incidence of in-hospital cardiopulmonary complications and a corresponding increase in patient survival rates. These benefits were achieved without an appreciable increase in the duration of hospitalization and with only modest increases in hospital cost, suggesting that thrombolytic therapy may offer a safe and effective alternative to operation in the initial treatment of patients diagnosed with acute limb-threatening peripheral arterial occlusion.

Clinical evaluation of stenosis of the carotid bifurcation with magnetic resonance angiographic techniques.

We evaluated the images of 60 carotid artery bifurcations in 31 patients suspected to have carotid artery disease who underwent invasive carotid angiography and combined two-dimensional, phase-sensitive and a gradient-echo magnetic resonance angiography. The phase scans consisted of seven serial projections that were obtained at 20 degrees intervals (11.0 minutes) around the carotid bifurcation; the gradient-echo (GRASS) scans were composed of 11 axial images (2.4 minutes) acquired through the bifurcation. The two magnetic resonance angiographic techniques yielded complementary pieces of information and were used together to compare magnetic resonance angiography with invasive angiography. Comparison of magnetic resonance and invasive angiograms of the 60 carotid arteries shows that the sensitivity (86%) and specificity (92%) of the magnetic resonance angiographic techniques we used to diagnose clinically significant carotid stenosis approach but do not reach those of invasive angiography.

Improved magnetic resonance imaging of the temporomandibular joint by oblique scanning planes.

This study was undertaken to investigate whether the quality of magnetic resonance images of the temporomandibular joint could be improved by scanning in oblique planes oriented according to the individual angle of the mandibular condyle (oblique images) instead of in the true anatomic sagittal and coronal planes (orthogonal images). Sagittal and coronal magnetic resonance images obtained by both methods in 21 patients were compared for image quality of the disk. In more than half the patients the oblique images demonstrated the anatomy of the disk better than the orthogonal images. Oblique images are therefore recommended.

Gadolinium-DTPA-enhanced magnetic resonance scanning in cerebellopontine angle tumors.

Magnetic resonance (MR) imaging has quickly emerged and already replaced computerized tomography (CT) in the evaluation of cerebellopontine angle (CPA) lesions, although even MR scanning may occasionally yield equivocal results. We recently studied six patients with a new MR image-enhancing contrast, gadolinium-DTPA (Gd-DTPA). All patients were suspected of having CPA pathology, and the standard MR scan was either negative, equivocal, or left unanswered questions regarding confirmed lesions. The Gd-DTPA-enhanced MR scan confirmed tumors or added useful information in five of six patients.

Reduced-bandwidth MR imaging of the head at 1.5 T1.

A decrease in the magnetic resonance (MR) imaging bandwidth can be used to increase the signal-to-noise ratio (S/N) at constant imaging time or to maintain the S/N for reduction of imaging time. The effect of bandwidth reduction from the default value of 16 kHz to 8 kHz was evaluated prospectively in 50 patients referred for MR imaging of the head. On intermediate (2,000/30 [repetition time msec/echo time msec]) and more T2-weighted (2,000/90) studies, there were no definite missed diagnoses and no diagnostically important changes in lesion characteristics when the reduced-bandwidth technique was used to obtain half- or quarter-time studies, excluding differences attributable to unintentional changes in patient position between image acquisitions. Chemical shift misregistration artifacts associated with reduced bandwidth are easily recognized with experience and do not interfere with diagnosis, as the artifacts occur in characteristic locations and diminish in most anatomic locations with increasing echo time. This study suggests the feasibility of reduced-bandwidth techniques in clinical MR imaging of the head at high field strength to achieve an increased S/N, to decrease imaging time, or to obtain images in additional projections.

Temporomandibular joint: MR assessment of rotational and sideways disk displacements.

The accuracy of coronal and sagittal magnetic resonance (MR) imaging was examined in the assessment of rotational and sideways displacements of the temporomandibular joint (TMJ) disk. Rotational disk displacement implies a combination of anterior and medial or lateral displacements, whereas sideways displacement implies pure medial or lateral displacement without an anterior component. Multiple 3-mm-thick coronal and sagittal MR images were obtained of 18 fresh TMJ autopsy specimens and compared with the observations in corresponding coronal cryosections. MR imaging correctly delineated the mediolateral position of the disk in 15 joints (83%) and incorrectly delineated it in three joints (17%). Osseous anatomy was correctly assessed in 17 joints (94%). On cryosections, six joints (33%) showed medial disk displacement and two joints (11%) showed lateral displacement. In five of these eight joints the medial or lateral displacement occurred in conjunction with an anterior displacement, that is, rotational displacement. Clinical MR imaging in 37 patients (61 joints with coronal images) showed medial or lateral disk displacement in 16 joints (26%). This study suggests that rotational and sideways displacements of the TMJ disk are an important aspect of internal derangement. The multiplanar capabilities of MR are suitable for an assessment of these abnormalities.

The role of catheters and guidewires in the production of angiographic thromboembolic complications.

Thromboembolic complications occurring during angiography may result from a number of different causes. Catheters and guidewires can interact with blood to form thrombi; this tendency is related to wall defects and the chemical composition and structural characteristics of the catheters and guidewires. Nonthrombic sources of emboli may consist of foreign bodies derived from surgical equipment or may exist in the flushing solution and contrast media. Plastic emboli may be shed from catheters and guidewires when the guidewires are passed through the catheters. Air emboli may result from poor technique or loose fitting connections between the catheter and injector or syringe; they can mimic emboli from catheters and guidewires. A number of strategies for decreasing the risk of thromboembolic complications during angiography are reviewed.

Anatomic findings and management of choanal atresia and the CHARGE association.

The CHARGE association is a collection of multisystem congenital anomalies including choanal atresia. A review of the literature failed to identify any specific findings that suggested the need to alter the management of choanal atresia in these patients. Our review of 24 patients with choanal atresia managed between 1974 and 1986 identified nine patients with the CHARGE criteria. These nine patients demonstrated a higher prevalence of surgical failures than the patients without the CHARGE association. The reasons are discussed, and computed tomographic scans demonstrate the anatomic findings of a more contracted nasopharynx and narrowed posterior choanal region. Thus, successful repairs require a more radical resection of the posterior nasal septum and lateral bony walls that can be achieved only with a transpalatal approach. The preoperative airways of CHARGE association patients are also at increased risk of obstruction and may require intubation or tracheotomy during the early life of the patient.

Clinical and arthrographic evaluation of temporomandibular joint sounds.

Two hundred five patients were examined for temporomandibular joint pain and dysfunction. Arthrograms were performed on 222 joints (188 unilateral and 17 bilateral). Patients with joint sounds suspected of being caused by meniscus displacement with reduction were evaluated. Seventy-two patients (38%), were suspected of "clicking" (a reducing meniscus), but only 53 had arthrographic findings of a reducing meniscus. Further evaluation of this patient group revealed that only 41 probably could be candidates for a protrusive splint. This represents only 57% (41 of 72) of patients with "clicking" who may be candidates for protrusive splint treatment.

Use of direct sagittal computed tomography in diagnosis and treatment of internal derangements of the temporomandibular joint.

Direct sagittal CT imaging of the TMJ provides several distinct advantages. Most significant is that direct imaging allows noninvasive evaluation of the disk. Direct sagittal CT scanning can confirm a clinical diagnosis of internal derangements as well as monitor splints intended for recapturing of the disk. Furthermore, the CT direct imaging allows excellent views of the bony architecture similar to those obtained with tomography. Used with clinical history and physical examination, CT can provide an excellent diagnostic modality to help provide better care for patients with internal derangement of the TMJ.