Kyoichi Imai

Preventive Effect of a Lactobacillus casei Preparation on the Recurrence of Superficial Bladder Cancer in a Double-Blind Trial

A double-blind trial was conducted in 138 patients with superficial transitional cell carcinoma of the bladder following transurethral resection to evaluate the prophylaxis of recurrence by an oral Lactobacillus casei preparation (BLP). Patients were stratified into the following 3 subgroups: (A) with primary multiple tumors; (B) with recurrent single tumors, and (C) with recurrent multiple tumors. In each group, patients were randomly allocated to receive BLP or placebo. BLP showed a better prophylactic effect in subgroups A and B than placebo, whereas no significant difference was observed in subgroup C. Cox multivariate analysis showed that the outcome with BLP was significantly better than with placebo (p = 0.01). Slight and tolerable adverse reactions occurred in 3 patients receiving BLP and in 3 of the placebo-treated patients. Oral administration of BLP was thus safe and effective for preventing recurrence of superficial bladder cancer.

Synthesis of low-molecular-weight copoly(l-lactic acid/ɛ-caprolactone) by direct copolycondensation in the absence of catalysts, and enzymatic degradation of the polymers

Low-molecular weight copolymers of l -lactic acid (LA) and ɛ-caprolactone (CL) were synthesized by direct copolycondensation without catalysts at 200°C under a nitrogen atmosphere. The reaction proceeds by direct condensation between linear LA and linear 6-hydroxycaproic acid produced by hydrolysis of the cyclic CL. These copolymers were characterized with respect to molecular weight by gel permeation chromatography, composition by 1 H nuclear magnetic resonance (n.m.r.) spectroscopy, sequence by 13 C n.m.r. spectroscopy, and crystallinities by both differential scanning calorimetry and X-ray measurement. The morphology of copoly (LA/CL) can be subdivided into three states as a function of monomer composition according to the differences in T g and crystallinity, e.g. solid (0–15 mol% CL composition ranges), paste (30–70 mol% CL composition ranges) and wax (85–100 mol% CL composition ranges). The in vitro degradation of the copolymer was examined by treatment in buffer solutions with and without enzymes and, as a result, Rhizopus delemer lipase showed the strongest degradation activity. In this case, the degree of enzymatic degradation is strongly dependent on the morphology of copoly(LA/CL), in which the pasty copolymer is much more subject to hydrolysis than the solid and waxy copolymers. For comparison the in vivo degradation of the copolymer was investigated by implanting it subcutaneously in the back of rats.

Diagnostic Significance of Prostate Specific Antigen and the Development of Mass Screening System for Prostate Cancer

PURPOSE The significance of prostate specific antigen (PSA) in the mass screening for prostate cancer was investigated. MATERIALS AND METHODS A total of 4,375 PSA, digital rectal and transrectal ultrasonographic examinations was performed on 3,526 subjects. RESULTS Among the 3 modalities, PSA had the highest sensitivity (80.4%) and positive predictive value (45.1%). We established age-specific reference PSA ranges for normal Japanese men, and demonstrated the significance of PSA density and PSA velocity. CONCLUSIONS The significance of PSA as a prostate cancer screening modality should be evaluated across multiple age ranges and in combination with previous PSA data and/or prostate volume.

In vivo characteristics of low molecular weight copoly (D,L-lactic acid) formulations with controlled release of LH-RH agonist.

Amorphous and crystalline copolymers with a relatively low molecular weight of 1800 were synthesized by direct copolycondensation of D-lactic acid and L-lactic acid in the absence of a catalyst, to evaluate their in vivo capabilities as biodegradable carriers for drug delivery systems. A luteinizing hormone-releasing hormone agonist, des-Gly10-(D-Leu6)-LH-RH ethylamide, was incorporated in a fine cylindrical copolymer formulation, under melt-pressing technique, a mild heat-pressure condition. This formulation was implanted subcutaneously in the back of male rats. The rate of in vivo degradation of amorphous copolymer was much faster than that of crystalline copolymer. Contrary to this tendency, the in vivo release of the drug from this amorphous formulation was held constant over a longer period, compared with the crystalline formulation. This can be closely related to the difference in dispersion of the drug in the formulation.

Endocrine Environment of Benign Prostatic Hyperplasia: Prostate Size and Volume are Correlated with Serum Estrogen Concentration

Estrogen plays an important role in the development of benign prostatic hyperplasia (BPH), as has been shown in both experimental and clinical studies. T determine the endocrine environment of BPH, serum total testosterone (Total-T), free testosterone (Free-T), and estradiol (E2) conceptions were measured, and the relationship between these levels and prostate size and volume was analyzed. Blood samples were collected from subjects who attended the mass screening for prostate disease performed by our institute. No significant correlations were found between Total-T levels, Free-T levels, and prostate size, as determined by digital rectal examination. However, E2 levels and the ratios for E2 levels and the ratios for E2/Total-T and E2/Free-T were significantly correlated with prostate size. To confirm these relationships, prostate volume was calculated from transrectal ultrasonographic images. E2 levels and these two ratios were, indeed, highly correlated with prostate volume. These results suggest that an estrogen-dominant environment plays an important role in the development of BPH.

In vivo controlled release of a luteinizing hormone-releasing hormone agonist from poly(dl-lactic acid) formulations of varying degradation pattern

Abstract Biodegradable formulations with a desired lag time were prepared from blends of low molecular weight poly( dl -lactic acid) (low MW-PLA, number-average molecular weight: M n = 1400 , parabolic-type degradation pattern, 100% in vivo degradation at 5th week of implantation) and high molecular weight poly( dl -lactide) (high MW-PLA, M n = 11 500 , S-type degradation pattern with a lag time of 10 weeks). A luteinizing hormone-releasing hormone agonist (LH-RH agonist), des-Gly10-[Leu6]LH-RH ethylamide monoacetate, was incorporated into the small cylinders of PLA blends. The initial burst of drug release from cylindrical formulation, which was implanted subcutaneously in the back of male rats, could be controlled by adjusting the amount of high MW-PLA in the blend and, as a result, it was found by measuring the pharmacological influence on rat prostate and serum drug levels that the best efficacy and the most constant release over a long period are obtained with a 25/75% low MW-PLA/high MW-PLA blend.

Correlation of prostate-specific antigen before prostate cancer detection and clinicopathologic features : Evaluation of mass screening populations

OBJECTIVES Although prostate-specific antigen (PSA) has become the reference standard for prostate cancer diagnosis, few reports have examined the long-term changes in PSA values before the diagnosis of prostate cancer in a large number of subjects. We investigated serial PSA levels and related values before prostate cancer diagnosis in a mass screening population and analyzed the values in an attempt to discover some values useful in clinical diagnostic science. METHODS We performed mass screening for prostate cancer in 9671 subjects from 1986 to 1998. The initial screening method was measurement of prostatic acid phosphatase from 1986 to 1991 and measurement of PSA from 1992 to 1998. As a result, 303 cases of prostate cancer were diagnosed. For all the cases diagnosed before 1991, we measured the serum PSA value in preserved frozen serum. RESULTS The prostate cancer detection rate was 3.1% among all subjects observed during the 13-year period. By measurement of the PSA level using frozen serum during the pre-PSA era, we found that 62% of patients demonstrated a PSA abnormality for more than 1 year (average 2.8) before prostate cancer diagnosis. Prostate cancer that was diagnosed within 1 year after a PSA value became abnormal was not associated with bone metastasis. Concerning the relationship between PSA velocity (PSAV) and clinical stage, the proportion of Stage B cancer was 86% in the subjects whose PSAV level before diagnosis was 0.18 ng/mL/yr or less and it was only 29% in those with PSAV levels of 4.5 ng/mL/yr or more. Only 3 (3.5%) of 86 patients with prostate cancer with PSAV levels of 4.4 ng/mL/yr or less had bone metastasis, and 2 of those 3 patients had poorly differentiated adenocarcinoma. CONCLUSIONS Although a total of 62% of patients had an abnormal PSA level more than 1 year before prostate cancer diagnosis, no patients with prostate cancer who were diagnosed within 1 year after the PSA level became abnormal had bone metastasis. Among patients who have undergone mass screening twice or more, a clinically useful indicator of the lack of bone metastasis would be a period between the detection of PSA levels of 4.1 ng/mL or more but not more than 10 ng/mL and prostate cancer diagnosis of less than 1 year and a diagnosis of well or moderately differentiated adenocarcinoma or a PSAV of 4.4 ng/mL/yr or less and a cancer diagnosis of well or moderately differentiated adenocarcinoma.

A new technique for transurethral resection of bladder tumors: rotational tumor resection using a new arched electrode.

PURPOSE A new technique of transurethral resection of bladder tumors is described. MATERIALS AND METHODS A 2.5 cm. papillary, sessile bladder tumor was treated via a rotational resection technique with a new arched electrode to replace longitudinal resection using a conventional loop electrode. RESULTS This method was easy to perform and allowed for en bloc resection of bladder tumor. CONCLUSIONS This rotational resection technique is useful for evaluation of pathological depth of tumors in resected specimens.

In vivo characteristics of high, molecular weight copoly(l-lactide/glycolide) with S-type degradation pattern for application in drug delivery systems

Amorphous copoly(L-lactide)/glycolide, 70/30 mol%) with weight average molecular weights of 16,900-41,300 were synthesized by ring-opening polymerization in the presence of catalysts using a molecular weight moderator lauryl alcohol. The in vivo degradation profiles of the copolyesters, which were evaluated by implanting them subcutaneously in the back of rats, showed a typical S-type degradation pattern. A luteinizing hormone-releasing hormone agonist (LH-RH agonist), des-Gly10-[Leu6]-LH-RH ethylamide monoacetate, was incorporated into the small cylinders of copoly (L-lactide/glycolide) with a weight average molecular weight of 24,000. The cumulative amount of drug released in vivo from the cylinders showed an S-type profile in analogy with the in vivo degradation pattern. This was demonstrated from data such as serum drug level and pharmacological influence on rat prostates.

Incidence of Urogenital Cancers in Gunma Prefecture, Japan: A 10‐Year Summary

Background: Although the incidence of urogenital cancers in Japan is lower than that of other cancers, it is increasing steadily. Thus, an epidemiologic study was necessary to determine the measures that would decrease the mortality rate associated with these cancers.