A Multicenter Phase I/II Study of the BCNU Implant (Gliadel ? Wafer) for Japanese Patients with Malignant Gliomas

Carmustine (BCNU) implants (Gliadel^® Wafer, Eisai Inc., New Jersey, USA) for the treatment of malignant gliomas (MGs) were shown to enhance overall survival in comparison to placebo in controlled clinical trials in the United States and Europe. A prospective, multicenter phase I/II study involving Japanese patients with MGs was performed to evaluate the efficacy, safety, and pharmacokinetics of BCNU implants. The study enrolled 16 patients with newly diagnosed MGs and 8 patients with recurrent MGs. After the insertion of BCNU implants (8 sheets maximum, 61.6 mg BCNU) into the removal cavity, various chemotherapies (including temozolomide) and radiotherapies were applied. After placement, overall and progression-free survival rates and whole blood BCNU levels were evaluated. In patients with newly diagnosed MGs, the overall survival rates at 12 months and 24 months were 100.0% and 68.8%, and the progression-free survival rate at 12 months was 62.5%. In patients with recurrent MGs, the progression-free survival rate at 6 months was 37.5%. There were no grade 4 or higher adverse events noted due to BCNU implants, and grade 3 events were observed in 5 of 24 patients (20.8%). Whole blood BCNU levels reached a peak of 19.4 ng/mL approximately 3 hours after insertion, which was lower than 1/600 of the peak BCNU level recorded after intravenous injections. These levels decreased to less than the detection limit (2.00 ng/mL) after 24 hours. The results of this study involving Japanese patients are comparable to those of previous studies in the United States and Europe.     

Pathophysiology,Diagnosis, and Treatment of Radiation Necrosis in the Brain

New radiation modalities have made it possible to prolong the survival of individuals with malignant brain tumors, but symptomatic radiation necrosis becomes a serious problem that can negatively affect a patient’s quality of life through severe and lifelong effects. Here we review the relevant literature and introduce our original concept of the pathophysiology of brain radiation necrosis following the treatment of brain, head, and neck tumors. Regarding the pathophysiology of radiation necrosis, we introduce two major hypotheses: glial cell damage or vascular damage. For the differential diagnosis of radiation necrosis and tumor recurrence, we focus on the role of positron emission tomography. Finally, in accord with our hypothesis regarding the pathophysiology, we describe the promising effects of the anti-vascular endothelial growth factor antibody bevacizumab on symptomatic radiation necrosis in the brain.     

Fungal Internal Carotid Artery Aneurysm Treated by Trapping and High-Flow Bypass: A Case Report and Literature Review

We report a case of unruptured fungal internal carotid artery (ICA) aneurysm and review the pertinent literature. A 79-year-old man presented with decreased visual acuity on the right side, and he was diagnosed with retrobulbar optic neuritis. Medical treatment with steroids resulted in Aspergillus meningoencephalitis spreading to the bottom of bilateral frontal lobes, caused by an intracranial extension of sphenoid sinusitis. Magnetic resonance imaging (MRI) performed 26 days after the start of antifungal therapy showed a denovo right ICA aneurysm projecting anteriorly into the sphenoid sinus. As the aneurysm grew rapidly, it was trapped surgically after establishing a high-flow bypass from the external carotid artery to the middle cerebral artery. The patient’s postoperative course was uneventful. Anti-fungal medication was continued until plasma concentrations of beta-D-glucan decreased to within normal limits. Although fungal ICA aneurysm carries a high mortality rate, early detection and prompt treatment by trapping and high-flow bypass can lead to good clinical outcome.     

Accidental dislocation of an intracaval temporary filter into the heart in a case of renal cell carcinoma extending into the vena cava

In a case of renal cell carcinoma extending into the vena cava, a temporary intracaval filter was applied before surgery to prevent pulmonary artery thrombosis. Two days later, the filter accidentally migrated into the right ventricle during defecation. Fortunately, it was successfully removed without damaging cardiac musculature under fluoroscopy.     

Long-term outcome of postoperative interferon-α adjuvant therapy for non-metastatic renal cell carcinoma

AIM: To investigate the long-term efficacy of postoperative interferon-alpha (IFN-alpha) adjuvant therapy in preventing recurrence in non-metastatic renal cell carcinoma treated with radical nephrectomy and to identify related prognostic markers. METHODS: Long-term follow-up was conducted to study rates of survival and non-recurrence in 88 subjects following radical nephrectomy for non-metastatic disease. RESULTS: The overall survival rate was 90% at 5 years and 88% at 10, with corresponding non-recurrence rates of 81% and 74%. Survival rates reviewed by preadministration pT stage showed a falling tendency from T1 through to T3 in line with pathological progression; when cases at stage pT1b or below were compared with those at stage pT2 or above, the latter showed a tendency to lower survival rates (P = 0.0966, Breslow-Gehan-Wilcoxon). Similarly, non-recurrence rates tended to fall in line with pathological progression, with a significant difference found in the comparison of cases at stage pT1b or below with those at stage pT2 or above (P = 0.0265, log-rank, Mantel-Cox). Duration of IFN-alpha administration showed a tendency to positive correlation with long-term survival (P = 0.3765, Breslow-Gehan-Wilcoxon). Non-recurrence rate was not found to differ according to duration of administration. Comparison of groups with normal and abnormal preadministration immunosuppressive acidic protein values showed that the normal group tended to have higher rates of survival and non-recurrence (P = 0.3371, Breslow-Gehan-Wilcoxon). CONCLUSIONS: Immunosuppressive acidic protein values appear to be a useful predictive marker for recurrence. A randomized trial, examining long-term outcome according to tumor stage and variables such as duration of administration, dose, administration time, and dosing schedule is required.     

Multiple tiny granulomatous lesions with eosinophils in a patient with smoldering-type adult T-cell leukaemia: The possibility of a new type of bronchioloalveolopathy

We herein describe the first case, to our knowledge, of pulmonary lesions characterized by necrotizing granuloma formation with eosinophils, in a patient with smoldering-type adult T-cell leukaemia. A 74-year-old man, diagnosed with smoldering-type adult T-cell leukaemia 1 year previously, was admitted due to repeated pyrexia and concurrent identification of diffuse small pulmonary nodules. A surgical lung biopsy specimen revealed inflammatory nodular lesions measuring up to 3 mm in size, which contained necrotizing and non-necrotizing granulomas, intraluminar organization and eosinophils, and were of unknown aetiology. The patient's condition, including the radiological findings, improved gradually without any treatment. This case suggests the possibility of a new type of human T-lymphotropic virus type-1 associated bronchioloalveolar disorder.     

Hand-assisted laparoscopic radical nephrectomy using intraoperative ultrasonography for left renal cell carcinoma involving a level I renal vein tumor thrombus

This report concerns two male patients, 65 (case 1) and 72 (case 2) years old, with a left renal tumor involving a level I renal vein tumor thrombus, who underwent hand-assisted laparoscopic radical nephrectomy using intraoperative ultrasonography. With the patient in the flank position, a midline supraumbilical hand port and two other ports were placed. Intraoperative ultrasonography identified the extent of the tumor thrombus. After hilar control, complete resection with intact removal was performed. Surgery lasted 305 min for case 1 and 237 min for case 2, with respective estimated blood loss of 410 mL and 572 mL. No postoperative complications occurred. Pathological examination showed a clear cell carcinoma with a level I tumor thrombus and negative surgical margins. Because the ultrasound probe can be easily inserted and the specimen can be extracted safely and intact, hand-assisted laparoscopic radical nephrectomy is practicable and effective for left renal cell carcinoma involving a level I renal vein tumor thrombus.     

Effects of the Calcium Antagonist AE0047 on the Development of Neurological Deficit and Infarction after Middle Cerebral Artery Occlusion in Stroke-prone Spontaneously Hypertensive Rats

AE0047 [4-(4-benzhydrylpiperazino)phenethyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine dicarboxylate dihydrochloride] is a new dihydropyridine calcium antagonist with protective effects against cerebral ischaemia and the occurrence of stroke in several animal models. We investigated the effects of AE0047 on focal ischaemia induced by middle cerebral artery occlusion in stroke-prone spontaneously hypertensive rats. AE0047 at a dose causing 20 or 40% systemic hypotension (1 or 3 mg kg^?) was given orally twice, 15 min and 24 h after occlusion. The neurological status of animals was investigated 2, 24 and 48 h after occlusion. Infarct area of brain was measured 48 h after occlusion. Middle cerebral artery occlusion resulted in the progressive deterioration of neurological status and large infarction in middle cerebral artery territories with 40% mortality. AE0047 dose-dependently attenuated the deterioration of neurological status, and reduced mortality to 0 or 10%. AE0047 significantly reduced infarct size and left/right hemispheric area ratio, an index of brain swelling. These results suggest that AE0047 has the ability to ameliorate ischaemic cerebral stroke in hypertensive patients.