Clinical experience with vestibular schwannomas: epidemiology, symptomatology, diagnosis, and surgical results

The Danish model for vestibular schwannoma (VS) surgery has been influenced by some historical otological events, taking its origin in the fact that the first attempt to remove CPA tumors was performed by an otologist in 1916. In approximately 50 years VS surgery was performed by neurosurgeons in a decentralized model. Highly specialized neuro- and otosurgeons have been included in our team since the early beginning of the centralized Danish model of VS surgery in 1976. Our surgical practice has always been performed on the basis of known and proven knowledge, but we spared no effort to search for innovative procedures. The present paper reflects the experience we have gained in two decades of VS surgery. Our studies on the incidence, symptomatology, diagnosis, expectancy and surgical results are presented. Received: 26 February 1997 / Accepted: 7 July 1997     

Persistent induction of nitric oxide synthase in tumours from mice treated with the anti-tumour agent 5,6-dimethylxanthenone-4-acetic acid.

An anti-tumour agent 5,6-dimethylxanthenone-4-acetic acid (5,6-MeXAA) induced nitric oxide synthase (NOS) in the tumour, spleen, thymus and small intestine, but not in the lung, liver, kidney, heart or skeletal muscle in B6D2F1 mice bearing subcutaneous colon 38 tumours. This pattern of induction is distinct from that caused by agents such as endotoxin, muramyl dipeptide or Corynebacterium parvum. The induction of NOS (iNOS) in the tumour was more persistent (maximal at 3 days) than in other tissues (maximal at 12 h). Immunohistochemical staining suggested that iNOS was located in macrophages and endothelial cells within and around the tumour. Treatment with 5,6-MeXAA also caused substantial increases in plasma nitrite and nitrate (NOx) concentrations that peaked at 8-12 h after 5,6-MeXAA. The increase in plasma NOx was prevented by a NOS inhibitor N-iminoethyl-L-ornithine (L-NIO), indicating that it was due to enhanced production of NO. Tumour-bearing mice were more responsive than controls to 5,6-MeXAA both in their plasma NOx increase and in their lower maximally tolerated dose. L-NIO was unable to prevent the complete tumour necrosis and regression caused by 5,6-MeXAA at a dose that substantially inhibited the increase of plasma NOx. In conclusion, the experimental anti-tumour agent 5,6-MeXAA induced NO synthesis in tumour-associated macrophages and in immunologically active tissues in parallel with its effects on tumour growth. The experiments with a non-selective NOS inhibitor L-NIO, however, suggest that NO is not a significant component in the mechanism of the anti-tumour action of 5,6-MeXAA in this particular model.     

Teniposide or carboplatin in patients with recurrent or advanced cervical carcinoma: A randomized phase II trial

Thomsen TK, Pfeiffer P, Bertelsen K. Teniposide or carboplatin in patients with recurrent or advanced cervical carcinoma: A randomized phase II trial. Int J Gynecol Cancer 1998; 8 : 310–314.
The aim of the present study was to investigate response rates, time to progression, and survival with teniposide or carboplatin in patients with advanced or recurrent cervical cancer and to estimate the toxicity of each drug regimen.
Twenty-eight patients with recurrent or advanced cervical cancer entered the study. Two patients were ineligible (severe renal impairment, n = 1; performance status 3, n = 1) and were excluded from the analysis. The remaining 26 patients were randomized to either carboplatin (400 mg/m² on day 1, intravenously every four weeks) or teniposide (125 mg/m² on days 1, 2 and 3, intravenously every four weeks). Twelve patients were randomized to the carboplatin arm and 14 patients to the teniposide arm. They were all comparable with respect to age, performance status, histology, primary FIGO stage, and prior therapy.
Response was seen in four patients in each group (33% and 29%, respectively), all but one being partial. (One patient in the teniposide group had complete response). Time to progression and median survival were similar in the two groups (median time to progression 20/17 weeks and median survival 40/41 weeks, respectively.)
In general, toxicity was moderate. Leukopenia (WHO grade 3 or 4) was seen in one patient treated with teniposide, and thrombocytopenia (WHO grade 3 or 4) in one patient treated with carboplatin. Eleven patients (79%) in the teniposide group had alopecia requiring a wig. The study implies that both drugs have some activity in cervical cancer. Carboplatin has the advantage that it can be administered on an out-patient basis.     

Gestational age, birth weight, and the risk of hyperkinetic disorder.

AIMS: To study the association between gestational age and birth weight and the risk of clinically verified hyperkinetic disorder. METHODS: Nested case-control study of 834 cases and 20 100 controls with incidence density sampling. RESULTS: Compared with children born at term, children born with gestational ages of 34-36 completed weeks had a 70% increased risk of hyperkinetic disorder (rate ratio (RR) 1.7, 95% confidence interval (CI) 1.2 to 2.5). Children with gestational ages below 34 completed weeks had an almost threefold increased risk (RR 2.7, 95% CI 1.8 to 4.1). Children born at term with birth weights of 1500-2499 g had a 90% increased risk of hyperkinetic disorder (RR 1.9, 95% CI 1.2 to 2.9), and children with birth weights of 2500-2999 g had a 50% increased risk (RR 1.5, 95% CI 1.2 to 1.8) compared with children born at term with birth weights above 2999 g. The results were adjusted for socioeconomic status of the parents, family history of psychiatric disorders, conduct disorders, comorbidity, and maternal smoking during pregnancy. Results related to birth weight were unchanged after adjusting for differences in gestational age. CONCLUSIONS: Children born preterm, also close to term, and children born at term with low birth weights (1500-2499 g) have an increased risk of clinically verified hyperkinetic disorder. These findings have important public health perspectives because the majority of preterm babies are born close to term.     

Increased fluorine-18 2-fluoro-2-deoxy-D-glucose (FDG) uptake in childhood CNS tumors is correlated with malignancy grade: a study with FDG positron emission tomography/magnetic resonance imaging coregistration and image fusion.

PURPOSE Positron emission tomography (PET) has been used in grading of CNS tumors in adults, whereas studies of children have been limited. PATIENTS AND METHODS Nineteen boys and 19 girls (median age, 8 years) with primary CNS tumors were studied prospectively by fluorine-18 2-fluoro-2-deoxy-D-glucose (FDG) PET with (n = 16) or without (n = 22) H(2)(15)O-PET before therapy. Image processing included coregistration to magnetic resonance imaging (MRI) in all patients. The FDG uptake in tumors was semiquantitatively calculated by a region-of-interest-based tumor hotspot/brain index. Eight tumors without histologic confirmation were classified as WHO grade 1 based on location, MRI, and clinical course (22 to 42 months). Results Four grade 4 tumors had a mean index of 4.27 +/- 0.5, four grade 3 tumors had a mean index of 2.47 +/- 1.07, 10 grade 2 tumors had a mean index of 1.34 +/- 0.73, and eight of 12 grade 1 tumors had a mean index of -0.31 +/- 0.59. Eight patients with no histologic confirmation had a mean index of 1.04. For these 34 tumors, FDG uptake was positively correlated with malignancy grading (n = 34; r = 0.72; P < .01), as for the 26 histologically classified tumors (n = 26; r = 0.89; P < .01). The choroid plexus papilloma (n = 1) and the pilocytic astrocytomas (n = 3) had a mean index of 3.26 (n = 38; r = 0.57; P < .01). H(2)(15)O-uptake showed no correlation with malignancy. Digitally performed PET/MRI coregistration increased information on tumor characterization in 90% of cases. CONCLUSION FDG PET of the brain with MRI coregistration can be used to obtain a more specific diagnosis with respect to malignancy grading. Improved PET/MRI imaging of the benign hypermetabolic tumors is needed to optimize clinical use.     

A Comparison Study of Vector Velocity,Spectral Doppler and Magnetic Resonance of Blood Flow in the Common Carotid Artery

Magnetic resonance phase contrast angiography (MRA) is the gold standard for blood flow evaluation. Spectral Doppler ultrasound (SDU) is the first clinical choice, although the method is angle dependent. Vector flow imaging (VFI) is an angle-independent ultrasound method. The aim of the study was to compare VFI- and SDU-estimated peak systolic velocities (PSV) of the common carotid artery (CCA) with PSV obtained by MRA. Furthermore, intra- and inter-observer agreement was determined. MRA estimates were significantly different from SDU estimates (left CCA: p?<?0.001, right CCA: p?<?0.001), but not from VFI estimates (left CCA: p?=?0.28, right CCA: p?=?0.18). VFI measured lower PSV in both CCAs compared with SDU (p?<?0.001) with improved precision (VFI: left: 24%, right: 18%; SDU: left 38%, right: 23%). Intra- and inter-observer agreement was almost perfect for VFI and SDU (inter-observer correlation coefficient: VFI 0.88, SDU 0.91; intra-observer correlation coefficient: VFI 0.96, SDU 0.97). VFI is more accurate than SDU in evaluating PSV compared with MRA.     

NEED FOR FACIAL REANIMATION AFTER OPERATIONS FOR VESTIBULAR SCHWANNOMA: PATIENTS PERSPECTIVE

A total of 779 patients operated on for vestibular schwannoma mostly by the translabyrinthine approach in Denmark during the period 1976-2000 answered a questionnaire about various postoperative consequences. In this paper we describe the patients' facial function evaluated by professionals one year postoperatively and self-evaluated by each patient according to the House-Brackmann scale at the time of the questionnaire. The patients' self-evaluation was more pessimistic than that of the professionals with 26% reporting House-Brackmann grade IV-VI, compared with 20%. One hundred and seventeen (15%) of 779 patients considered their facial palsy to be a big problem and 125 patients (16%) were interested in surgical treatment for the sequelae of facial palsy. Seventy-eight (10%) had already had some kind of operation, usually the VII-XII coaptation. Thirty-three of 61 patients who had already been operated on for facial palsy were interested in further surgical treatment. One hundred and ninety-five patients (25%) had some kind of operation on the eye, mostly (88%) a tarsorrhaphy. Reanimation procedures such as a palpebral gold weight or a spring, apparently still have a small place in Denmark. In conclusion, there seem to be a considerable and unmet need for surgical reanimation of facial function in patients with facial palsy after operations for vestibular schwannoma in Denmark.