Ching-Kuo Lin

The conditional probabilities of survival in patients with anaplastic astrocytoma or glioblastoma multiforme

BACKGROUND By the use of conditional probabilities of survival, we studied the yearly survival rates for individual tumor survivors. METHODS Conditional survival rate was estimated in 114 consecutive patients with anaplastic astrocytoma or glioblastoma multiforme. Conditional probabilities of surviving some years given survival to a specific period of time after craniotomy and 95% confidence intervals were calculated in the individual tumor survivors. RESULTS The estimated median survival was 30 months for 45 patients with anaplastic astrocytoma and 12 months for 69 patients with glioblastoma multiforme. The conditional probabilities of surviving next one year given survival to 1 year, 2 years, 3 years, 4 years, or 5 years after craniotomy for anaplastic astrocytoma were 86.2%, 75.0%, 85.9%, 77.8%, or 85.7%, respectively; for glioblastoma multiforme 64.8%, 58.7%, 85.7%, 80.0%, or 75.0%, respectively. The conditional probability of surviving to 5 years given survival to 2 years after craniotomy for anaplastic astrocytoma, i.e., surviving an additional 3 years, was 50.1%, which was better than observed 5-year survival rate (28.6%); for glioblastoma multiforme it was 40.2%, which also was better than observed 5-year survival rate (12.4%). CONCLUSIONS The conditional probability of survival was a good method to clinically predict yearly survival rate for individual tumor survivors. In addition, the method can estimate the probabilities of surviving next some years given survival to a specific period of time after craniotomy. It also showed a more encouraging result than observed survival rate in patients with supratentorial malignant astrocytomas.

Simultaneous multiple hypertensive intracerebral haemorrhages

Background.Simultaneous occurrence of multiple intracerebral haemorrhages (ICHs) in different arterial territories is a rare clinical event which has been reported to be associated with cerebral amyloid angiopathy, venous sinus thrombosis, coagulopathy, vasculitis, haemorrhagic transformation of cerebral infarcts and multiple intracranial pathologies such as vascular anomalies or tumours. Although hypertension is the most common etiological factor for the development of spontaneous single intracerebral bleeding, its role in simultaneous multiple ICHs is not clear.Methods. The authors have reviewed all patients with non-traumatic ICH admitted to Kaohsiung Medical University Hospital from 1993 to 2002. Ten hypertensive patients with simultaneous multiple ICHs were found. For the purpose of comparison, another 600 cases with solitary hypertensive ICH were also reviewed as a control group. Computerized tomographic scans and medical records concerning patients’ histories, clinical presentations, locations of haematomas, associated risk factors, and outcome were analyzed.Findings. The mean age and sex distribution were similar in both patient groups. Bilateral putaminal or thalamic haemorrhages were the most common combinations of simultaneous bleedings. As for the individual location of haematoma, there was a strong preponderance for the supratentorial space with the thalamus being the most preferable site. The duration of hypertension was longer and the percentage of previous stroke was higher in patients with multiple ICHs. Other associated risk factors were similar in both groups except for higher incidence of hypercholesterolemia in multiple ICHs group. Patients with simultaneous multiple ICHs had a much worse outcome compared to those with solitary ICH.Conclusions. As with solitary ICH, hypertension is still the most important etiological factor for simultaneous multiple ICHs. The widespread and prolonged degeneration of intracerebral arterioles predispose patients to the development of multiple ICHs, which could be justified by the longer history of hypertension and higher incidence of former strokes. Only hypercholesterolemia was identified to be significantly associated with this unusual brain event in our study. The mechanism underlying the development of simultaneous multiple ICHs is not clear although structural and haemodynamic changes of first haemorrhage may be responsible for the second one. Poorer outcome in patients with multiple ICHs can be explained by the concomitant destruction of crossing and non-crossing fiber tracts and bilateral diaschisis phenomenon.

Factors influencing seizures in adult patients with supratentorial astrocytic tumors

SummarySeizures and epilepsy in adults are important and increasingly common clinical problems. Despite this, the investigation of seizures in adults with astrocytic tumors remains a grey area. The incidence and influencing factors of preoperative and postoperative seizures were evaluated in 101 patients of 45 years or older with supratentorial astrocytic tumors. Preoperative seizures occurred in 14 (14%) patients. Seizures at presentation were significantly correlated with pathological grades of astrocytic tumors (p=0.0318). The risk of seizures at presentation was greatest in patients with well-differentiated astrocytomas as compared with anaplastic astrocytomas (Odds ratio=4.364, p=0.056) or glioblastomas multiforme (Odds ratio=5.673, p=0.007). There was no association of preoperative seizures with age, sex, location or site of the tumors. Postoperative seizures occurred in 18 (18%) patients, including 8 (8/14, 57%) recurrent seizures and 10 (10/87, 12%) late-onset seizures. Postoperative seizures were significantly correlated with the presence of preoperative seizures (p=0.0003). The presence of preoperative seizures was potentially predictive of postoperative seizures when evaluated by logistic regression model (Odds ratio=6.650). Thirteen (72%) of 18 patients with postoperative seizures were associated with tumor recurrence in 7 cases, hemorrhage in 3 cases and malignant progression in 3 cases. There was no association of postoperative seizures with age, sex, location or site of the tumors, grades of tumors, type of preoperative seizures, duration of preoperative seizures, serum level of anticonvulsant drug, extent of surgery, postoperative radiation or chemotherapy. The patients with preoperative seizures had a higher risk of postoperative seizures and should be carefully monitored. Imaging examination of brain to exclude the possibilities of tumor recurrence or hemorrhage is warrantable in supratentorial astrocytoma patients with postoperative seizures.

Rac2 expression and mutation in human brain tumors.

SummaryBackground. Rac1 and Rac2 are interchangeable in NADPH oxidase activation. Rac1 plays an important role in regulating nuclear signalling and in the activation of transcriptional factors that regulate gene expression and cell growth. Our previous study observed mutation in effector region of Rac1 gene in brain tumors. Little is known about the expression and mutation of Rac2 in human brain tumors.Method. We examined the expression of Rac2 by using reverse transcriptase-polymerase chain reaction (RT-PCR) and northern blot analysis and the mutation of Rac2 gene by using DNA sequence analysis.Findings. The decreased expression of Rac2 was found in 15 cases (57.7%) including 8 of 10 astrocytomas, 2 of 8 meningiomas, and 5 of 8 pituitary adenomas. Two of 13 cases with decreased expression of Rac2 had gene mutation. Only two of 26 cases had Rac2 overexpression in which no Rac2 gene mutation was found. Four of 8 cases with normal Rac2 expression had Rac2 gene mutation. The site of Rac2 gene mutation had no hot spots and was not concentrated in the effector region.Conclusions. Our results showed a low frequency of mutation and no hot spots of mutation in Rac2 gene in brain tumors, suggesting a decreased possibility of Rac2 in the brain tumorigenesis. The role of high frequency of decreased Rac2 expression in brain tumors, particularly in malignant astrocytomas, needs further investigations to be elucidated.

Primary spinal tumors in children

Nine patients, 16 years of age or younger with primary spinal cord tumors, diagnosed between 1991 and 2003 at The Kaohsiung University Hospital, were reviewed retrospectively. There were 2 female and 7 male patients. Two tumors were located primarily in the cervical cord (1 meningioma, 1 neurofibroma), five were predominantly thoracic (1 lymphoma, 1 meningioma, 1 astrocytoma, 1 fibrosarcoma and 1 osteoblastoma), one lumbar (ependymoma), and one sacral (Ewings sarcoma). The most common clinical presentation was limb weakness (100%) followed by back pain (44.4%). All the patients underwent laminectomy for removal of their tumors. Five children with benign tumors improved postoperatively. At discharge, these 5 children could walk without assistance and have remained stable with long-term of follow-up. Radical surgery should be considered in benign primary spinal cord tumors. As would be expected, patients diagnosed and treated early and in whom a total resection was achieved had a better prognosis.

The effect of an adenosine A1 receptor agonist in the treatment of experimental subarachnoid hemorrhage-induced cerebrovasospasm

SummaryBackground. Adenosine is a potent vasodilator and an important modulator of cardiovascular function. It has been postulated that nitric oxide (NO) is involved in adenosine-induced vasodilation. This study was designed to examine the effect of an adenosine A1 agonist, N6-cyclopentyladenosine (CPA), in the prevention of subarachnoid haemorrhage (SAH)-induced vasospasm. Method. Experimental SAH was induced in Sprague-Dawley rats by injecting 0.3 mL autogenous blood into the cisterna magna. Intraperitoneal injections of CPA (0.003 mg/kg), or vehicle were administered 5 min and 24 hours after induction of SAH. The degree of vasospasm was determined by averaging the cross sectional areas of the basilar artery 2 days after SAH. Expressions of endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) in basilar artery were evaluated. Findings. There were no significant differences among the control and treated groups in physiological parameters recorded before sacrifice. When compared with animals in the control group, cross-sectional area of basilar arteries areas in the SAH only, SAH plus vehicle and SAH plus CPA groups were reduced by 19% (p < 0.01), 22% (p < 0.01), and 9% (p = 0.133), respectively. The cross-sectional areas of the CPA-treated group differed significantly from those of the SAH only and SAH plus vehicle group (p < 0.05). Induction of iNOS-mRNA and protein in basilar artery by SAH was not significantly diminished by CPA. The SAH-induced suppression of eNOS-mRNA and protein were relieved by CPA treatment. Conclusions. This is the first evidence to show an adenosine A1 receptor agonist is effective in partially preventing SAH-induced vasospasm without significant cardiovascular complications. The mechanisms of adenosine A1 receptor agonists in attenuating SAH-induced vasospasm may be, in part, related to preserve the normal eNOS expression after SAH. Inability in reversing the increased iNOS expression after SAH may lead to the incomplete anti-spastic effect of CPA.

Delayed administration of the K+ channel activator cromakalim attenuates cerebral vasospasm after experimental subarachnoid hemorrhage.

Summary¶ Background. Delayed cerebral vasospasm remains an unpredictable and inadequately treated complication of aneurysmal subarachnoid hemorrhage (SAH). Recent evidence indicates that the potassium channel activator cromakalim is capable of limiting cerebral vasospasm in rabbits when administered immediately after experimental SAH (i.e. before spastic constriction has been initiated). However, the ultimate clinical value of cromakalim for treating vasospasm will depend in part on its effectiveness when administered after SAH-induced constriction has already been initiated. The present study examined the effects of cromakalim on vasospasm when treatment was initiated after SAH-induced constriction was underway. Methods. New Zealand white rabbits were subjected to experimental SAH by injecting autologous blood into the cisterna magna. Cromakalim (0.03, 0.1 or 0.3 mg/kg) or vehicle was injected intravenously at 8 hour intervals beginning 24 hours post-SAH. Animals were killed by perfusion fixation 48 hours after SAH. Basilar arteries were removed and sectioned, and cross-sectional area was measured. Findings. The average cross sectional areas of basilar arteries were reduced by 64% and 68% in the SAH-only and SAH+vehicle groups, respectively. Treatment with cromakalim dose-dependently attenuated SAH-induced constriction. The groups treated with 0.03, 0.1, and 0.3 mg/kg cromakalim exhibited average decreases in cross-sectional area of 57%, 42%, and 19%, respectively. Interpretation. These findings indicate that cromakalim dose-dependently attenuates cerebral vasospasm when administered 24 hours after experimental SAH in the rabbit. The results suggest KATP channel activators, such as cromakalim, could be of benefit for reversing cerebral vasospasm after aneurysmal SAH.

Hemorrhagic cerebellar metastasis from papillary thyroid carcinoma.

Papillary thyroid carcinoma has a low incidence of distant metastases. Brain metastasis is extremely rare with a frequency of 0.1-1.3%. In the present series, the rate was 1.5%, only two cases had cerebral metastases in 136 patients with papillary thyroid carcinoma from January 1988 to April 1998. Cerebellar metastasis is even rarer, and solitary cerebellar metastasis has not been reported to the best of our knowledge. Two cases of papillary thyroid carcinoma with cerebellar metastases presenting as tumor hemorrhage are reported. In one patient, the lesion was in the bilateral cerebellar hemispheres with obstructive hydrocephalus. After operation, the patient had an uneventful course with recovery of her consciousness. In the other, the solitary lesion was in the left cerebellar hemisphere without obstructive hydrocephalus. After surgical treatment, the patient had a smooth course with resolution of his neurological deficit. It shows the importance of surgery in the management of a hemorrhagic cerebellar metastasis from papillary thyroid carcinoma, not only in reducing acute aggravating cerebral symptoms, but also in prolonging survival time.

Rapid Resolution of Infantile Acute Subdural Hematoma: A Case Report

Subdural hematomas in infants are uncommon but usually result from non‐accidental trauma or from trauma associated with motor vehicle accidents. This report describes the case of an infant with a traumatic acute subdural hematoma that resolved within 65 hours. A 23‐month‐old boy fell from a height of approximately 10 m. Brain computed tomography disclosed a left subdural hematoma with midline shift. The associated clots resolved spontaneously within 65 hours of the injury. Although they may mimic more clinically significant subdural hematomas, such collections of clots are likely to be located at least partly within the subarachnoid space. Their recognition may influence decisions regarding both surgical evacuation and the likelihood of non‐accidental injury. Clinical and radiographic features distinguishing these “disappearing subdural hematomas” from more typical subdural hematomas are discussed.

A comparison of propofol target controlled infusion-based and sevoflurane-based anesthesia in adults undergoing elective anterior cervical discectomy and fusion

The target controlled infusion (TCI) of propofol with fentanyl facilitates easy titration of the depth of anesthesia, and thereby may improve the quality of anesthesia. The aim of this study is to investigate if propofol TCI‐based anesthesia is practical for anterior cervical discectomy and fusion (ACDF), one of the most common surgical interventions in spine procedures, when compared with sevoflurane‐based anesthesia with respect to the quality of anesthesia. Patients were classified into two groups according to the anesthesia regimen of maintenance of anesthesia with fentanyl and either propofol TCI (group FP) or inhalational sevoflurane (group FS), respectively. The primary endpoint was to evaluate quality of anesthesia and extubation time. Secondary endpoints were hemodynamic stability during the operation, operative fentanyl consumption, and postoperative complications. The study results revealed there were comparable results on time to extubation, changes in intraoperative hemodynamic parameters, and the occurrence of postoperative complications between the groups. No differences in average length of intensive care unit (ICU) stay and hospital stay were noticed. However, opioid consumption and blood loss during the operation for patients in group FP were significantly higher than those of patients in group FS (551.28 ± 193.98 vs. 446.86 ± 177.15 μg, p = 0.005; 52.06 ± 58.25 vs. 28.33 ± 40.74 mL, p = 0.019, respectively). In these adult patients undergoing ACDF, propofol TCI‐based anesthesia appears to be as efficacious as sevoflurane‐based anesthesia but consumed more fentanyl and experienced higher blood loss.