Brain metastases from asymptomatic adenocarcinoma of the pancreas: an autopsy case report

BACKGROUND: Brain metastasis from pancreatic cancer is extremely rare. Because pancreatic cancer usually has a rapidly progressive nature, the majority of affected patients die from primary lesions before exhibiting clinical signs suggestive of brain metastases. CASE DESCRIPTION: The patient was a 62-year-old man who developed generalized convulsion followed by right hemiparesis accompanied by decreased consciousness level. Computed tomography (CT) scan revealed multiple brain tumors with ring-like contrast enhancement. Stereotactic biopsy disclosed mucinous adenocarcinoma. A marked increase in the serum CA19-9 level was noted, but the patient did not exhibit any other signs of pancreatic disease. Repeated whole body CT scan and ultrasonography demonstrated no primary lesions. The patient died of multi-organ failure during chemotherapy combined with radiation for metastatic brain tumors. Autopsy revealed well-differentiated papillary adenocarcinoma in the pancreatic head and systemic metastases associated with tumor emboli were widely distributed in various organs. CONCLUSION: This patient initially presented only with symptoms of neurologic disorder and no pancreatic symptoms. Moreover, repeated radiologic examinations did not reveal the primary lesion. We considered that the unusual clinical course in our patient may be partly explained by the autopsy findings: diffuse sclerotic changes of the pancreas without swelling. The present report suggests that undetected pancreatic cancer may have been the primary lesion classified as "unknown origin" in some cases of metastatic brain tumors.     

Rapid regrowth of solitary subependymal giant cell astrocytoma--case report

A 48-year-old female presented with a subependymal giant cell astrocytoma (SEGA) without tuberous sclerosis manifesting as memory and mental disturbance. Magnetic resonance imaging showed a huge mass which was well-demarcated and extended from the anterior horn of the right lateral ventricle to the septal area on the right side. Surgery was performed with partial removal of the tumor. The histological diagnosis was typical SEGA. One year postoperatively, follow-up magnetic resonance imaging revealed marked regrowth of the tumor. Total resection of the tumor was performed. Microscopic and immunohistochemical studies could not identify the cause of the rapid regrowth. SEGA can regrow rapidly after partial removal of the tumor.     

A study of the substrate specificity of Na+-dependent and Na+-independent neutral amino acid transport systems in dog intestinal brush-border membrane vesicles using L-alanine analogues

Neutral amino acids are mainly transported across the intestinal brush-border membrane by two Na+-dependent systems (system B0 and system B0+) and one Na+-independent system (system b0,+). To investigate potential differences in substrate specificity between these systems, we screened ten different alanine analogues for their ability to inhibit the transport of L-alanine in dog intestinal brush-border membrane vesicles. The results suggested that a phenyl group directly attached to the alpha-carbon has different effects on the Na+-dependent and Na+-independent transport systems, with an increased affinity for the former and a decreased affinity for the latter. Based on these inhibition studies, we investigated [14C]L-phenylglycine transport kinetics in comparison with L-alanine. Similar to L-alanine, L-phenylglycine transport followed at least three routes, however, the Km of the Na+-dependent transport system was lower and the K'm of the Na+-independent system was higher than the corresponding values for L-alanine. These results corroborated the conclusions drawn from the inhibition studies. Based on these data, we conclude that different sizes of immediate parts to the alpha-carbon in functional groups of amino acid analogues have differential effects on the interaction of these amino acid analogues with the Na+-dependent and Na+-independent transport systems for neutral amino acids.     

A mixture of ethylene vinyl alcohol copolymer and ethanol yielding a nonadhesive liquid embolic agent to treat cerebral arteriovenous malformations: initial clinical experience

OBJECT: The authors report their clinical experience with their new nonadhesive liquid embolic agent, an ethylene vinyl alcohol copolymer (EVAL)/ethanol mixture, to treat arteriovenous malformations (AVMs). METHODS: Between June 1995 and April 2001, 57 patients with confirmed AVMs underwent embolization of their lesions with the EVAL/ethanol mixture. In 87 procedures consisting of one to three stages, the authors embolized 185 feeding arteries to occlude as much of the AVM as possible. Repeated injections under fluoroscopic control could be performed smoothly without encountering cementing of the catheter to the vessel wall. Among the 87 embolizations undertaken in 57 patients, seven procedures (8%) in six patients produced new postembolization symptoms. Resolution of these symptoms occurred within hours or days after four of the seven procedures; permanent neurological deficits remained after the other three procedures (3.4%). Of the 57 patients, three underwent postembolization radiosurgery, and 54 underwent radical treatment with microsurgical extirpation. Histopathological examination of the 54 specimens disclosed mild inflammation within the embolized lumen without inflammatory reactions in the media or adventitia. Follow-up angiograms obtained 3 years after radiosurgery was administered showed that in all three patients treated in this fashion the nidus had completely disappeared. CONCLUSIONS: The EVAL/ethanol mixture is handled easily and appears to be an effective and safe agent for preoperative embolization of AVMs.     

A nonadhesive liquid embolic agent composed of ethylene vinyl alcohol copolymer and ethanol mixture for the treatment of cerebral arteriovenous malformations: experimental study

OBJECT: The authors have developed a mixture of ethylene vinyl alcohol copolymer (EVAL) and iopamidol, which is dissolved in ethanol, as an alternative solvent to provide a safe means of embolizing arteriovenous malformations (AVMs). METHODS: A two-stage delivery technique is required to prevent premature precipitation in the catheter when using this material: the catheter is first infused with 30% ethanol and this is followed by the delivery of the EVAL-ethanol mixture. Acute angiographic changes were analyzed after superselective delivery of dimethyl sulfoxide (DMSO) and 30% ethanol into the renal artery of rabbits. Histological changes following the embolization of the renal artery achieved using the EVAL-ethanol mixture were recorded at 1 hour and at 2 and 16 weeks after the procedure. Although DMSO always produced severe, rapidly progressive vasospasm in the renal artery during a 1- to 60-minute postinfusion, 30% ethanol did not. Microscopically, the lumens of embolized vessels examined 1 hour after embolization with EVAL-ethanol appeared to be filled with EVAL sponges, leaving almost no open spaces. The space between the EVAL sponges and the inner surface of the vessels was filled with fresh thrombus. In the vessel walls of specimens examined 2 weeks after embolization there was no or a slight inflammatory reaction. Scattered in the EVAL sponges were almost equal numbers of neutrophilic granulocytes and mononuclear cells, indicative of a mild inflammatory response. In specimens examined 16 weeks postembolization, the changes noted at 2 weeks were intensified. There was no definite histopathological evidence of mural hemorrhage, perivascular extravasation of the mixture, or perivascular hemorrhage in any specimen that was examined. CONCLUSIONS: Although the degree of permanence of this embolization material is yet unknown, the mixture was easy to handle, and appeared safe and effective for AVM embolization. Its nonadhesive characteristic and its ability to be infused by repeated injections make it an attractive alternative to currently available materials. The good results obtained in this study led us to undertake a clinical trial, the results of which are contained in a companion article in this issue of the Journal of Neurosurgery.     

Analysis of homozygous deletion of the p16 gene and correlation with survival in patients with glioblastoma multiforme

OBJECT: One of the most frequent genetic abnormalities found in patients with glioblastoma multiforme (GBM) is homozygous deletion of the p16 tumor suppressor gene. The authors investigated whether this deletion is associated with prognosis in patients with GBM. METHODS: In 46 adult patients with supratentorial GBM, homozygous deletion of the p16 gene in tumor DNA was examined using the multiplex polymerase chain reaction assay. The deletion was confirmed in 14 (30.4%) of 46 patients, eight (30.8%) of 26 men and six (30.0%) of 20 women. Cox proportional hazard regression analysis, adjusted for age at surgery, the Karnofsky Performance Scale score, extent of resection, and the MIB-1 labeling index. revealed that homozygous deletion of the p16 gene was significantly associated with overall survival and progression-free survival in men, but not in women. CONCLUSIONS: The results of this study suggest that p16 homozygous deletion is a significant unfavorable prognostic factor in male patients with GBM.     

Appropriate interval between embolization and surgery in patients with meningioma

BACKGROUND AND PURPOSE: The best time for surgery after embolization of meningiomas remains unclear. We used the tumor-softening effect of embolization to determine this time. METHODS: Forty-two patients with intracranial meningiomas that received more than 50% of their blood supply from the external carotid artery underwent embolization before surgery. The interval between embolization and surgery and the tumor consistency at the time of surgery were recorded. The interval between embolization and surgery was divided into 3-day segments, and an average tumor consistency score was obtained in segments. Patients were assigned to two groups: group 1 underwent surgery on a specified day after embolization; group 2 underwent surgery at a later date. We compared tumor consistency, blood loss, length of hospitalization, surgical resection time, Simpson grade at surgery, and complication rate in both groups. RESULTS: On the polynomial regression curve, greatest tumor softening occurred 7-9 days after embolization. When the postembolization interval exceeded 10 days, no further softening occurred. Compared with group 1 patients, group 2 patients did not have an increased blood loss, a longer hospitalization, or a higher complication rate. In group 2, the surgical procedure required less time, and the Simpson grades were lower. CONCLUSION: In meningiomas that receive more than 50% of their blood supply from the external carotid artery, the optimal interval between embolization and surgery is 7-9 days. This interval allows the greatest degree of tumor softening, which makes it possible to remove the tumor more safely and easily.     

The utility of the microcrystalline cellulose sphere as a particulate embolic agent: an experimental study

BACKGROUND AND PURPOSE: Although various particulate materials have been developed as embolization agents, their biocompatibility remains unclear. We used an animal model to examine the possibility of using FDA-approved microcrystalline cellulose spheres (CELPHERE) as solid embolic material for the permanent occlusion of blood vessels. METHODS: Angiographic and histologic studies in 12 canine renal arterial systems were conducted to evaluate the performance of CELPHERE beads at 1 hour, and at 4 and 12 weeks after embolization. RESULTS: The CELPHERE beads traveled to vessels with diameters approximating their own. Larger vessels were occluded by aggregations of beads. There was no disruption of vessel walls and no evidence of perivascular hemorrhage or inflammatory changes. CONCLUSION: Because CELPHERE beads are easy to handle, highly biocompatible, and have few adverse effects, they are suitable for intravascular applications.     

Temporal sequence of response to unilateral GPi pallidotomy of motor symptoms in Parkinson's disease

The present study was performed to determine the temporal sequence of the response to unilateral MRI/microelectrode-guided pallidotomy of each cardinal symptom in Parkinson's disease (PD). For this purpose, we performed a quantitative assessment of motor functions in 19 patients with PD at several time points up to 6 months following surgery. We here report that although all the motor signs were significantly improved 6 months after pallidotomy, the temporal sequence of tremor response was different from those of other symptoms.