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Objective: This study compared the antitumor effect, adverse effects and survival between transcatheter arterial embolization (TAE) and transcatheter arterial infusion chemotherapy (TAI) in patients with hepatocellular carcinoma (HCC). Methods: The study population consisted of 168 consecutive patients with advanced HCC treated with transcatheter arterial treatments using cisplatin suspended in lipiodol. Among these, 74 patients were treated with TAE, and the remaining 94 patients were treated with TAI. Results: There were no significant differences in any baseline characteristics except hemoglobin, platelets, albumin, and glutamic pyruvic transaminase. Complete or partial tumor response was achieved in 54 patients (73%) in the TAE group and in 48 patients (51%) in the TAI group (p < 0.01). There were two treatment-related deaths caused by acute hepatic failure and acute renal failure in the TAE group. Nausea and deterioration of serum transaminase after TAE were significantly more severe than after TAI. Median survival time and survival rates at 5 years were 3.1 years and 25% in the TAE group, and 2.5 years and 18% in the TAI group (p = 0.37). Conclusion: TAE has a higher antitumor effect than TAI, but does not significantly improve the survival of patients with HCC.

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Background and AimsIn mammalian spermatogenesis, glial cell line-derived neurotrophic factor (GDNF) is one of the major Sertoli cell-derived factors which regulates the maintenance of undifferentiated spermatogonia including spermatogonial stem cells (SSCs) through GDNF family receptor α1 (GFRα1). It remains unclear as to when, where and how GDNF molecules are produced and exposed to the GFRα1-positive spermatogonia in vivo.Methodology and Principal FindingsHere we show the cyclical and patch-like distribution of immunoreactive GDNF-positive signals and their close co-localization with a subpopulation of GFRα1-positive spermatogonia along the basal surface of Sertoli cells in mice and hamsters. Anti-GDNF section immunostaining revealed that GDNF-positive signals are mainly cytoplasmic and observed specifically in the Sertoli cells in a species-specific as well as a seminiferous cycle- and spermatogenic activity-dependent manner. In contrast to the ubiquitous GDNF signals in mouse testes, high levels of its signals were cyclically observed in hamster testes prior to spermiation. Whole-mount anti-GDNF staining of the seminiferous tubules successfully visualized the cyclical and patch-like extracellular distribution of GDNF-positive granular deposits along the basal surface of Sertoli cells in both species. Double-staining of GDNF and GFRα1 demonstrated the close co-localization of GDNF deposits and a subpopulation of GFRα1-positive spermatogonia. In both species, GFRα1-positive cells showed a slender bipolar shape as well as a tendency for increased cell numbers in the GDNF-enriched area, as compared with those in the GDNF-low/negative area of the seminiferous tubules.Conclusion/SignificanceOur data provide direct evidence of regionally defined patch-like GDNF-positive signal site in which GFRα1-positive spermatogonia possibly interact with GDNF in the basal compartment of the seminiferous tubules.

SM-11355 is a platinum complex developed to treat hepatocellular carcinoma (HCC). It is administered via the hepatic artery, using a carrier, lipiodol, that consists of ethyl esters of iodized poppy seed oil. We have performed a phase I clinical trial of an SM-11355-lipiodol formulation in 11 HCC patients, in order to investigate the maximum allowable dose and to maximize the efficacy and safety of the drug in the treatment of HCC. The SM-11355 arterial infusion suspension was administered at doses of 6, 12 and 20 mg ml À1 in a maximum lipiodol volume of 6 ml. An antitumour efficacy rating of complete response was achieved for one patient and a partial response rating was achieved for a second patient, giving an overall response rate of 18.2%. Anorexia, nausea and vomiting, pyrexia, thrombocytopenia and increases in AST, ALT and total bilirubin were observed as adverse effects, but each was transient and each patient had recovered completely by 4 weeks after drug administration. Hence, we concluded that the maximum allowable dose was not reached in this study. Overall, our results suggest that SM-11355 is effective in treating HCC and we suggest that the dose for early phase II trials should be 20 mg ml À1 .

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