Placebo-controlled, double-blind study of the non-purine-selective xanthine oxidase inhibitor Febuxostat (TMX-67) in patients with hyperuricemia including those with gout in Japan: phase 3 clinical study.

BACKGROUND: : Allopurinol has been widely used for treatment of hyperuricemia, however, it may be associated with various adverse effects. Febuxostat has been identified as a potentially safe and efficacious alternative. OBJECTIVES: : A multicenter study with randomized, placebo-controlled, double-blind, parallel-group comparison was carried out to evaluate the efficacy and safety of febuxostat in 103 patients with hyperuricemia (including patients with gout) in Japan. METHODS: : Subjects were treated with febuxostat (20 or 40 mg/d) or a placebo for 8 weeks. The variables evaluated were the percentage of patients achieving serum uric acid levels 6.0 mg/dL or less and the percent change in serum uric acid levels after 8 weeks. RESULTS: : The percentage of patients achieving serum uric acid levels 6.0 mg/dL or less after 8 weeks was 91.2% in the febuxostat 40-mg/d group, 45.7% in the 20-mg/d group, and 0.0% in the placebo group. The percent changes in serum uric acid levels after 8 weeks were -44.9% in the febuxostat 40-mg/d group, -28.9% in the 20-mg/d group, and -0.6% to -0.5% in the placebo group. No severe or medically significant adverse reaction attributable to febuxostat was noted, and there was no event that could pose a clinical problem. The efficacy did not differ depending on the presence/absence of gout history. CONCLUSIONS: : These results suggest that febuxostat (20 or 40 mg/d) is useful as a new means of treating hyperuricemia and is capable of reducing serum uric acid levels to 6.0 mg/dL or less (goal of treatment) with high safety regardless of the presence/absence of gout history.

Placebo-controlled double-blind dose-response study of the non-purine-selective xanthine oxidase inhibitor febuxostat (TMX-67) in patients with hyperuricemia (including gout patients) in japan: late phase 2 clinical study.

BACKGROUND: Allopurinol has been widely used for the treatment of hyperuricemia, however, it may be associated with various adverse effects. Febuxostat has been identified as a potentially safe and efficacious alternative. OBJECTIVES: A multicenter study with randomized, placebo-controlled, double-blind, parallel, intergroup comparison was carried out to evaluate the dose-response relationship, efficacy, and safety of febuxostat in 202 patients with hyperuricemia (including patients with gout) in Japan. METHODS: The subjects were treated with febuxostat at fixed maintenance doses (20-80 mg/d) or a placebo for 16 weeks. The percentage of patients achieving serum uric acid levels 6.0 mg/dL or less and the percent change in serum uric acid levels after 16 weeks of treatment were evaluated. RESULTS: The percentage of patients achieving serum uric acid levels 6.0 mg/dL or less at 16 weeks was 87.8% in the 80-mg/d dose group, 83.3% in the 60-mg/d group, 82.9% in the 40-mg/d group, 46.5% in the 20-mg/d group, and 2.6% in the placebo group (P < 0.001, Mantel-Haenszel test). A statistically significant dose-response relationship was found. The percent change in serum uric acid levels after 16 weeks of treatment differed significantly between each febuxostat dose group and the placebo group and increased in a dose-dependent manner above 40 mg/d. No deaths, events posing a clinical problem, or serious adverse reactions attributable to febuxostat were noted. Similar results were obtained regardless of gout history. CONCLUSIONS: Febuxostat can safely reduce serum uric acid levels to 6.0 mg/dL or less in 80% or more of patients with hyperuricemia (including gout) at doses of 40 mg/d or higher.

An allopurinol-controlled, multicenter, randomized, open-label, parallel between-group, comparative study of febuxostat (TMX-67), a non-purine-selective inhibitor of xanthine oxidase, in patients with hyperuricemia including those with gout in Japan: phase 2 exploratory clinical study.

BACKGROUND: Allopurinol has been widely used for the treatment of hyperuricemia, however, it may be associated with various adverse effects. Febuxostat has been identified as a potentially safe and efficacious alternative. OBJECTIVES: Febuxostat was administered to patients with hyperuricemia including gout in Japan to compare its efficacy and safety with those of allopurinol. METHODS: The starting dose of febuxostat and allopurinol was 10 and 100 mg/d, respectively, and was increased to the fixed maintenance dose of 40 or 60 mg/d for febuxostat and 300 mg/d for allopurinol for 16 weeks. RESULTS: : The percent change in the serum uric acid level at 16 weeks compared with the baseline serum uric acid level was -42.96% ± 13.33% and -52.47% ± 9.79% for the febuxostat 40- and 60-mg/d groups, respectively, and -36.55% ± 18.59% for the allopurinol group, indicating that the hypouricemic effects of febuxostat increased in a dose-dependent manner and equaled to or surpassed those of allopurinol (P = 0.0239, 2-sample t test). The percentage of patients with serum uric acid levels of 6.0 mg/dL or less at 16 weeks was 88.9% and 100% for the febuxostat 40- and 60-mg/d groups, respectively, and 68.8% for the allopurinol group, showing higher achievements for the febuxostat groups compared with the allopurinol group. All adverse drug reactions were mild to moderate in severity, and there were no severe symptoms or reactions leading to drug discontinuation. CONCLUSIONS: These results suggest that febuxostat is safe at doses of 40 and 60 mg/d and has equal or greater efficacy than 300 mg/d allopurinol.

Evaluation of the Outcome of Laparoscopic Radical Prostatectomy by a Single Surgeon: Experience with an Initial 30 Cases / Journal of Rural Medicine

Objective: We carried out this study to clarify whether operative methods of laparoscopic prostatectomy (LRP) could become a standard therapy. The purpose was to evaluate the technical feasibility, oncologic effectiveness and perioperative and postoperative morbidity of LRP performed by a general urologist. Patients and Methods: Between June 2004 and May 2006, 30 patients with clinically localized prostate cancer consecutively underwent LRP by a single surgeon. Oncologic data were assessed by histopathological examination and by postoperative prostate-specific antigen (PSA) levels. Results: Complete laparoscopic removal of the prostate and seminal vesicles was achieved in all 30 patients. The average operation time was 250.9 min (range, 168 to 394 min). The total positive surgical margin rate was 20.7% (6 of 29 cases), with a total PSA recurrence rate was 23.3% (7 of 30 cases), but the frequencies tended to be decreased in the later phase cases. Perioperative complications were encountered in 5 patients; four of these patients were in the initial 10 cases. Two of the 30 cases (6.7%) required a blood transfusion (first case and 11th case). There were three surgical complications, one ureter injury, one rectal injury and one sigmoid serosal injury. The catheter duration intervals were reduced in the later cases. Conclusions: From our experience with one surgeon, with whom perioperative complications were concentrated in the initial 10 cases, we conclude that LRP should be performed by experienced surgeons after intensive training.

Clear Cell Sarcoma of the Kidney: A Case Report of an 11-year-old Boy and A Review of 11 Cases in Japan / Journal of Rural Medicine

An 11-year-old boy experienced right flank pain on October 12, 2005. The pain was once alleviated but recurred on the following day, and the patient visited our hospital on October 13, 2005. An imaging study revealed a tumor, sized approximately 12.0 × 7.5 × 8.0 cm, in the right kidney without metastases, for which right nephrectomy was performed. The tumor was solid, although degenerative necrosis and hemorrhage were partially observed inside the tumor. A histopathological study revealed poorly-defined, almost round tumor cells which were strongly stained with vimentin but not with cytokeratin or epithelial membrane antigen (EMA). Based on these findings, a diagnosis of clear cell sarcoma of the kidney in Stage II was made. A review of 10 previous cases reported in Japan during the past 10 years revealed that the affected patients were mostly aged 1 month to 4 years, while our case, occurring in an 11-year-old patient, was uncommon in respect to age.

Effect of Neoadjuvant Hormonal Therapy of Surgical Margin Status in Patients with Prostate Cancer Treated by Radical Prostatectomy / Journal of Rural Medicine

(Objective) Neoadjuvant hormonal therapy (NHT) before radical prostatectomy promotes the downstaging of primary lesions. A retrospective analysis was conducted of the relationship between NHT durations and positive surgical margin rates, as well as between positive surgical margin rates and three types of prostatectomy (antegrade radical prostatectomy, retrograde radical prostatectomy, and laparoscopic radical prostatectomy (LRP)).;(Materials and Methods) This study was a retrospective analysis of 257 patients treated with radical prostatectomy during the three years between April 2002 and March 2005. Of the 257 patients, 190 were treated by NHT. NHT durations were classified into “not conducted,” “<1 month,” “1-3 month,” “3-6 month” and “>6 month,” and the relationship between positive surgical margin rates and NHT durations was investigated. Seventy-four patients underwent antegrade radical prostatectomy, 131 were treated with retrograde radical prostatectomy, and 52 underwent LRP. Positive surgical margin rates were investigated according to the types of prostatectomy, as well as according to prostate-specific antigen (PSA) levels upon diagnosis.;(Results) Positive surgical margin rates were 53.8% in the “not conducted” and “<1 month” groups, 38.8% in the “1-3 month” group, 32.4% in the “3-6 month” group, and 10.7% in the >6 month” group. Positive surgical margin rates after open surgery (antegrade and retrograde) tended to decrease when NHT durations were longer, while those after LRP tended to increase inversely. No correlation was observed between PSA levels upon diagnosis and positive surgical margin rates or between presurgical PSA levels and NHT durations.;(Conclusion) Positive surgical margin rates were not significantly different when patients were treated with NHT for 1-3 months, but they tended to decrease when NHT was for >6 months. However, positive surgical margin rates after LRP increased when NHT continued for longer periods of time. This may the result of fibrous adhesion in the vicinity of the prostate due to long-term NHT which made the surgical margins unclear.

Early-Stage Clinical Experiences of Holmium Laser Enucleation of the Prostate (HoLEP) / Journal of Rural Medicine

Objective: Recently, holmium laser enucleation of the prostate (HoLEP) has been established as one method of endoscopic surgery for the treatment of benign prostate hyperplasia (BPH). The purpose of our study was to assess initial clinical experiences with HoLEP at our hospital.;Patients and Methods: A retrospective analysis was conducted of 28 patients with obstructive symptoms due to BPH who underwent HoLEP during the 13 months between February 2004 and March 2005.;Results: The mean age of the patients was 67.4 years (range 59 to 78 years). The mean enucleation tissue weight was 24.3 g (range 2 to 95 g), and the average operation time was 94.1 minutes (range 40 to 268 minutes). The mean duration of postoperative catheterization was 3.4 days (range 1 to 6 days). The mean urine flow rate improved, and each patient's satisfaction for voiding, measured on a 5-point scale, was good. There were no major complications during the operations except one case, which was completed with TUR-P because of uncontrollable bleeding. No patients required transfusions. Long-term complications included five cases of stress incontinence (19%), four of urethral stricture (14%), and three temporary retention, two of which required re-catheterization (10%).;Conclusion: HoLEP can be performed without major intraoperative complications. It is an effective treatment for obstructive symptoms due to BPH. However, there are many postoperative problems that must be resolved, including stress incontinence and urethral stricture because of our lack of experience, with HoLEP.

Giant Bladder Stone Transurethrally Removed in One Piece Without Urethral Injury / Journal of Rural Medicine

We operated on an 87-year-old female suffering from a giant bladder stone. Her chief complaint was fever and lower abdominal pain, which was caused by lodgement in the urethra. The stone was easily removed in one piece without breakage or injury to the urethral orifice and urethra using forceps normally used for grasping bones in orthopedics. The stone measured 75×50×45 mm and was composed of magnesium ammonium phosphate. To our knowledge, this is the largest bladder and/or urethral stone that was transurethrally removed without being broken. Thus, forceps that are normally used for grasping bones in orthopedics can be used to remove giant bladder stones without leaving stone fragments.