[Prospective randomized trial comparing 1/2 FAM (5-fluorouracil (5-FU) + adriamycin + mitomycin C) versus palliative therapy for the treatment of unresectable pancreatic and biliary tract carcinomas (the 2nd trial in non-resectable patients). Japanese Study Group of Surgical Adjuvant Therapy for Carcinomas of the Pancreas and Biliary Tract].

The efficacy of 1/2 FAM, which consists of 5-fluorouracil (5-FU), adriamycin (ADM) and mitomycin C (MMC), was compared with that of palliative treatment in patients with unresectable pancreatic and biliary tract carcinomas in a multicenter randomized trial. The patients assigned to 1/2 FAM group were treated with 5-FU 200 mg/m2/day IV, ADM 15 mg/m2/day IV and MMC 5 mg/m2/day IV. These 3 drugs were given concurrently as the initial dose within a week after palliative operation, and this regimen was repeated for at least 2 whole courses, at 4-week intervals before the next course of therapy. Those randomized to the control group were subjected to palliative treatment alone. Completely eligible for analysis were 42 cases of the 1/2 FAM group and 41 of the control group. There was no significant difference between the groups with respect to the overall and differentiated survival times according to the tumor sites and the clinical efficacy. As for the duration of 50% inhibition of tumor progression, a significantly better outcome was obtained in 1/2 FAM group. Tumor progression was most significantly inhibited in patients with gallbladder carcinoma. In 1/2 FAM group, tumor reduction was achieved in 1 CR and 2 PR patients. The most frequent adverse reaction was gastrointestinal manifestations, along with diarrhea and alopecia. 1/2 FAM did not contribute to the life prolongation, but inhibited the tumor progression for a significantly longer duration and, to a lesser extent, reduced the tumor size in unresectable pancreatic and biliary tract carcinomas. This regimen is suggested to be useful particularly in the treatment of the latter carcinoma.

Hyperthermic treatment of canine tibia through RF inductive heating of an intramedullary nail: a new experimental approach to hyperthermia for metastatic bone tumours.

Although the incidence of metastatic bone tumours is recently increasing, the local control rate of conventional treatment modalities is not satisfactory. If an intramedullary nail for the fixation of a weakened bone with metastatic lesions can be used as a heat-generating material for hyperthermia, the treatment result is expected to improve. This new approach to hyperthermic treatment of bone tumours has been investigated in a canine tibia. An intramedullary nail made of stainless steel was put into a medullary canal of a canine tibia. The leg was exposed to an alternating magnetic field of 100 kHz in the frequency and 100 Oe in the maximum intensity. The nail was inductively heated for 60 min. The temperature of the nail > 50 degrees C and the cancellous bone 5 mm from the nail was heated to a therapeutic temperature, 42.5 degrees C. After a bone labelling with tetracycline and calcein, the dogs were killed 2, 4 and 12 weeks after the heating. The area of osteonecrosis was evaluated by fluorescence microscopy analysis. The heated cancellous bone around the nail showed osteonecrosis in 2 weeks after the treatment, but it recovered completely in 12 weeks. This experiment has demonstrated the heating capability of the new hyperthermic technique and minimal toxicity to the bone, and suggests the clinical application to metastatic bone tumours.

Localized hyperthermic treatment of experimental bone tumors with ferromagnetic ceramics.

Localized hyperthermic treatment was carried out with use of a metastatic bone tumor model in rabbits. The experimental bone tumor was created by transplantation of pieces of tumor line VX2 into the medullary canal of rabbit tibiae. Two weeks after the transplantation, a ferromagnetic ceramic pin was inserted in the medullary canal. Then, hyperthermia (HT) of the tumor was accomplished with use of an alternating magnetic field for 50 min. All the rabbits were killed 5 weeks after tumor transplantation, and the therapeutic effect was evaluated histologically and roentgenographically. Almost all the tumor cells within the bone marrow were killed by this procedure. The area of tumor necrosis in the HT group was significantly larger than in the control group. The pathological fracture rate and displacement rate were reduced significantly by this treatment (38.5 and 0%) compared with the controls (92.3 and 92.3%). Therefore, HT with the use of ferromagnetic ceramics was effective for local control of malignant bone tumors and seems to be a promising new method of treatment.

A heat-generating bioactive glass-ceramic for hyperthermia.

Glass plates of the chemical composition: CaO (29.0), SiO 2 (31.0), Fe 2O 3 (40.0), B 2O 3 (3.0), P 2O 5 (3.0) in weight ratio were heated to 1050 degrees C at a rate of 5 degrees C/min and then cooled to laboratory temperature. The resulting glass-ceramic containing magnetite and wollastonite crystals showed high-saturation magnetization. The bonding ability of this new glass-ceramic to bone tissue was evaluated using rabbit tibiae, and compared with glass of the same composition. This glass-ceramic formed a Ca, P-rich layer on its surface and bonded tightly with bone within 8 weeks of implantation. However, the glass did not form this Ca, P-rich layer, nor had it bonded with bone at 25 weeks. The bone-heating ability of this glass-ceramic was investigated by applying a max. 300-Oe, 100-kHz magnetic field. The granules of the glass-ceramic filled in the rabbit tibiae heated the whole surrounding bone to more than 42 degrees C and maintained this temperature for 30 min. Bioactive ceramics reinforce the mechanical strength of bone tissue. Furthermore, this heat-generating bioactive glass-ceramic can be used for hyperthermic treatment of bone tumors.

Low wear rate of UHMWPE against zirconia ceramic (Y-PSZ) in comparison to alumina ceramic and SUS 316L alloy.

Partially stabilized zirconia ceramic is being recognized among ceramics for its high strength and toughness. With this ceramic, is possible to manufacture a 22-mm-size femoral head for low friction arthroplasty of the hip joint in association with an ultra-high-molecular-weight polyethylene socket. Wear-resistant properties of zirconia ceramic were screened on two principally different wear devices. Sterile calf bovine serum, physiological saline, and distilled water were chosen as the lubricant fluid media. Depending on the lubricant medium, the wear factor of polyethylene against zirconia ceramic counterfaces was 40 to 60% less than that against alumina ceramic counterfaces, and 5 to 10 times lower than with the SUS316L metal counterfaces. Polyethylene wear against metal was more susceptible in saline in which it had 2 to 3 times higher wear rate than with serum. On the other hand, different fluid media had little effect on polyethylene wear against ceramic counterfaces. In each set of tests, the wear factor obtained on an unidirectional wear device showed 10 to 15 times higher values, in comparison to the wear factor estimated on a reciprocating wear device.

Bone-bonding ability of P2O5-free CaO.SiO2 glasses.

An apatite- and wollastonite-containing glass-ceramic (A.W-GC) has been reported to form a tight bond with living bone through an apatite layer formed on its surface. This layer is considered to be formed by dissolution of Ca2+ and HSiO3- ions from the glass-ceramic into the surrounding body fluids. In order to confirm this proposed mechanism for the surface reaction of A.W-GC, three kinds of glass in the systems CaO-SiO2, CaO-SiO2-CaF2, and CaO-SiO2-P2O5 were implanted into the tibiae of rabbits for 3 or 8 weeks. Contact microradiography and SEM-EPMA showed that all three kinds of glass formed a Ca,P-rich layer in combination with a Si-rich layer on their surfaces within 3 weeks and formed a direct bond with bone via these layers. The detaching test, performed 8 weeks after implantation, showed that the loads required to detach the implants from the bone were almost equal for the phosphorus-free and the phosphorus-containing glasses. It was concluded that even P2O5-free CaO.SiO2 glass formed a Ca,P-rich layer on its surface and bonded tightly with living bone. If glasses and glass-ceramics release at least Ca2+ and HSiO3- ions, this would be sufficient for them to form the Ca,P-rich layer on their surfaces in vivo, enabling them to bond directly with bone.

Bone bonding behavior of bead-coated alumina ceramic under load-bearing conditions.

Alumina ceramic has good biocompatibility, high mechanical strength, and excellent lubrication properties. However, it is bioinert and does not bond with bone tissue. Therefore, to promote mechanical bonding, we have developed an alumina ceramic material coated with alumina ceramic beads using identical alumina ceramic binder. In this study, we evaluated the bone bonding capability of this material under load-bearing conditions along with its mechanical properties. The test pieces with or without bead-coating were implanted into the load-bearing portions of the medial and lateral femoral condyles of adult mongrel dogs. The dogs were euthanized 4, 8, and 24 weeks after implantation, and the pull-out test and histological examination were performed. The uncoated implants showed signs of loosening similar to those observed clinically. In contrast, the bonding strength of the bead-coated implants was significantly greater than that of the uncoated implants and increased with implantation time. This increase in strength differs from the results obtained in the non-load-bearing experiments, in which a plateau was seen relatively early after implantation. Results of histological examination suggested that this increase was caused by thickening of ingrown trabeculae, which could be observed as early as 4 weeks after implantation, at the bone-implant interface. In addition, the mechanical properties of the bead-coated alumina ceramic were comparable to those of grooved alumina ceramic which has been used clinically. These results indicate the possibility for clinical application of the bead-coated alumina ceramic.

Strengthening of bone-implant interface by the use of granule coatings on alumina ceramics.

Three different granule coatings (a granular alumina ceramic coating, a granular hydroxyapatite coating, and a polished granular hydroxyapatite coating) applied to alumina ceramic substrate were evaluated for their strengthening effects of the bone-implant interface in rabbit tibiae. For a comparison, noncoated alumina ceramics, and dense hydroxyapatite were assessed in the same way. The granular alumina ceramic coating, creating a bioinert, porous surface, was most effective due to a strong mechanical bond between the bone and implant. The interface strength was even higher than that of the dense hydroxyapatite. The granular hydroxyapatite coating, creating a bioactive, porous surface, was less effective than the granular alumina ceramic coating because of the brittleness of the hydroxyapatite granules, although it formed a direct and mechanical bond with bone tissue. The polished granular hydroxyapatite coating, creating a bioactive, smooth surface, was least effective because of the brittleness of the hydroxyapatite granules, though it presented an improved interface strength compared with that of the noncoated alumina ceramics due to a direct bond between the bone and hydroxyapatite granules.

A method for toxicological evaluation of biomaterials based on colony formation of V79 cells.

This report describes a method for cytotoxicity screening of biomaterials based on colony formation of V79 cells. For this test, two metals (titanium and nickel), two ceramics (alumina ceramic and tricalcium phosphate), and two types of polymeric material [high density polyethylene (HDP) and polyvinylchloride (PVC)] were used. Each metal and ceramic was cast into a disk and semidisk 49 mm in diameter and 1 to 2 mm thick. The HDP was molded into a petri dish and PVC was used as a thin film. The materials were sterilized by heating or with ethylene oxide and placed in plastic petri dishes, after which 8 ml cell suspension containing 100 cells were added to each dish. After 1 week, the colonies formed on the materials were fixed, stained, and then the number of colonies was counted. Titanium, alumina ceramic, and HDP showed no differences from the controls in terms of colonies. On the disks and the semidisks of nickel and tricalcium phosphate and on the thin disks of PVC, however, no colonies were detected. The V79 cells used in this experiment showed a rapid and logarithmically stable growth curve and such a high rate of colony formation as to form visible noticeable colonies, and were therefore suitable cells for screening test the cytotoxicity of biomaterials. Unlike other previously reported methods of in vitro cytotoxicity testing, this method permits assay of colonies formed from a single cell after proliferation directly on the materials. Moreover, the test with semidisks permits simple screening to assess the cytotoxicity is caused by either the chemical substances or the physical properties of the materials.(ABSTRACT TRUNCATED AT 250 WORDS)