A multicenter Phase II study of sorafenib in Japanese patients with advanced hepatocellular carcinoma and Child Pugh A and B class.

OBJECTIVE: To evaluate prospectively the efficacy and safety of sorafenib, which has been the first-line treatment for advanced hepatocellular carcinoma (HCC), in Japanese HCC patients (pts) with not only Child-Pugh (C-P) A class but also C-P B class. METHODS: Sorafenib was administered orally at the dose of 400 mg twice daily for pts with HCC and liver function of C-P score of 5-8. Administration was continued until the detection of disease progression or appearance of unacceptable toxicity. The primary endpoint was time to progression (TTP), and toxicity and the secondary endpoints included objective response, overall survival (OS). RESULTS: Forty C-P A pts and 12 C-P B pts were enrolled. The median TTP in the C-P A pts and C-P B pts was 3.3 months and 3.2 months, respectively. Among the pts with C-P A, complete response, partial response, and stable disease were achieved for 2.5%, 7.5% and 47.5%. Among the pts with C-P B, there were no treatment responses, 66.7% of pts had stable disease. The median OS in the C-P A pts and C-P B pts was 13.4 months and 7.4 months, respectively. With regard to toxicities, fewer C-P A pts experienced Grade 3/4 toxicities than C-P B pts (77.5% vs. 91.6%). There were no treatment-related deaths in either group of patients. CONCLUSIONS: This study shows sorafenib has similar effectiveness in the recent post-approval studies and is well-tolerated in Japanese pts with HCC and Child Pugh A class. Sorafenib should be used with great care for Child Pugh class B pts.

Differences in the extent of primary ischemic damage between middle cerebral artery coagulation and intraluminal occlusion models.

The authors studied the differences between heat-shock/stress protein 70 (hsp70) gene expression and protein synthesis in the unilateral middle cerebral artery (MCA) microsurgical direct occlusion (Tamura's) model and the unilateral intraluminal occlusion model. In Tamura's model, expression of hsp70 mRNA and HSP70 protein and decreased protein synthesis were detected in the ischemic areas, including the ipsilateral cortex and caudate. These phenomena, however, were not observed in the areas outside the MCA territory, including the ipsilateral thalamus, hippocampus, and substantia nigra. These results were consistent among the experimental rats. In the intraluminal occlusion model, however, induction of both hsp70 mRNA and HSP70 protein and impairment of protein synthesis were noted in the areas outside the MCA territory, including the ipsilateral thalamus, hypothalamus, hippocampus, and substantia nigra, as well as in the MCA territory, including the ipsilateral cortex and caudate. These results were not consistent among the experimental rats. These different results might be due to widespread damage resulting from internal carotid artery (ICA) occlusion in the intraluminal occlusion model. Accordingly, the authors suggest that this model be called an ICA occlusion model, rather than a pure MCA occlusion model.

Development of Japanese neurosurgery: from the Edo era to 1973.

IN JAPAN, ALTHOUGH eminent surgeons have performed major operations while the patient is under general anesthesia since the end of the 18th century and the beginning of the 19th century, neurosurgical operations were performed only sporadically for many years after 1877. The Japanese Neurological Society was formed in 1948. Independent departments of neurosurgery have been established since 1962. The Board of Neurological Surgery was founded in 1966. The Fifth International Congress of Neurological Surgery, held in Tokyo in 1973, strongly influenced young Japanese neurosurgeons.