Kumon, Hiromi

We performed laparoscopic prostatectomy in seven cases with organ-confined prostate cancer. In 6 cases, the surgery was completed successfully and the mean operative time was 424 min. Volume of blood loss was 200 to 3,200 ml and catheterization lasted 6 to 37 days. No major complications were observed in 6 of the cases. In one case, open surgical conversion was necessary mainly due to a bladder injury. Although these were the first cases of laparoscopic prostatectomy in our institution, the technical difficulty and complexity of the surgery were moderate. We believe that laparoscopic radical prostatectomy will become a standard option for the treatment of organ-confined prostate cancer.

From January 2004 to March 2007, 308 patients with clinically localized prostate cancer were treated using iodine-125 (125I) seed implantation (permanent brachytherapy) at Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences. We evaluated the treatment’s effi cacy and morbidity in 300 prostate cancer patients who were followed up for more than 1 month after brachytherapy. Based on the National Comprehensive Cancer Network (NCCN) guidelines, patients with a prostate volume of less than 40 ml in transrectal ultrasound imaging were classifi ed as low or intermediate risk. The median patient age was 67 years (range 50 to 79 years), the median prostate-specific antigen (PSA) value before biopsy was 6.95 ng/ml (range 1.13 to 24.7 ng/ml), and the median prostate volume was 24.33 ml (range 9.3 to 41.76 ml). The median follow-up was 18 months (range 1 to 36 months) and the PSA levels decreased in almost all patients after brachytherapy. Although 194 of 300 patients (64.7%) complained of diffi culty in urination, pollakisuria/urgency, miction pain, and/or urinary incontinence, all of which might be associated with radiation prostatitis during the fi rst month after brachytherapy, these symptoms gradually improved. 125I seed implantation brachytherapy is safe and eff ective for localized prostate cancer within short-term follow up.

We report on 64 patients who did not achieve erections adequate for satisfactory sexual intercourse from among a total of 243 patients who were prescribed PDE5 inhibitors for erectile dysfunction (ED). Intracavernous injection (ICI) of PGE was performed in this non-responder group. An ICI of 20 or 40 mcg of PGE1 in 1 ml saline was performed and the responses evaluated. Forty-nine out of 64 (77 percent ) cases responded to 20 mcg of PGE1. Forty mcg of PGE was injected into the 15 non-responding cases, and 9 patients responded favorably. The overall effective rate was 58/64 (91 percent ). No major adverse effects were observed.

To evaluate morbidity in Hybrid Radical Prostatectomy (HRP, hybridized laparoscopic and open retropubic radical prostatectomy). The operative and pathological outcomes obtained in 25 consecutive patients who underwent HRP were reviewed. The median operating time was 220min, median blood loss was 550ml, and no patient required an allogenic blood transfusion. No severe postoperative complications were observed. The surgical margin was positive in 12% of all patients, and in 1 patient with pT2 or less (4.5%). These results indicate that HRP is safe and may be able to combine the benefits of both laparoscopic and open procedures.

A total of 252 bladder-washing and voided specimens from normal, and inflammatory and malignant lesions were examined by a direct mapping technique, i.e., a combined use of light (LM) and scanning electron microscopy (SEM). A newly-designed mesh, which consists of a piece of gelatine-covered, osmium-impregnated and polylysine-coated glass-slip with 42 compartments/25 mm2, was used in this study. This mesh permitted us to directly correlate LM and SEM images, which resulted in a shortening of the observation time. Malignancy of exfoliated urothelial cells has been determined on the basis of the presence or absence of pleomorphic microvilli as observed by SEM. Subsequently, a new "SEM grading" system for human urinary cytology was proposed. The direct mapping technique has enhanced the accuracy of the diagnosis over conventional methods, especially in cases of noninvasive, low-grade malignant tumors of the urinary bladder.

We retrospectively evaluated the subjective and objective treatment results of transurethral microwave thermotherapy (TUMT) for benign prostatic hyperplasia (BPH) and explored the difference in effectiveness between 30- and 60-min single treatments. From June 1997 through March 2003, 58 men with BPH underwent TUMT using the Targis device. Twenty-seven and 31 patients each received a single treatment of 60 or 30 min, respectively. Evaluations after treatment included a clinical determination of the International Prostate Symptom Score, urodynamic assessments by peak flow rate, and magnetic resonance imaging (MRI). In the 60-min treatment, the symptom score improved significantly, from 17.9 to 9.5 after 2 months. Similarly, there was a significant improvement in peak flow rate, from 6.7 to 11.2 ml/sec after 2 months. In the 30-min treatment, the symptom score also improved significantly, from 18.4 to 13.4 after 2 weeks. Similarly, there was a significant improvement in the peak flow rate, from 6.4 to 11.7 ml/sec after 1 month. MRI imaging showed necrosis of the prostate gland 2 weeks after either treatment. These results demonstrated that both the 60-min and the 30-min treatments were effective for patients with BPH. Moreover, the 30-min treatment led to quicker improvement than the 60-min treatment. Thus, a 30-min TUMT protocol is considered recommendable for this treatment.

Urinary tract infections (UTIs) due to fluoroquinolone-insusceptible Escherichia coli have become increasingly common in recent years. We investigated the potential relationships between clinical measures to combat fluoroquinolone-insusceptible E. coli and experimental analyses on E. coli isolates. Over a 14-year period from 1994 through 2007, a total of 828 E. coli isolates were collected from patients (one isolate per patient) with UTI at the urology ward of Okayama University Hospital. We analyzed the mutations in quinolone resistance-determining regions of DNA gyrase (gyrA) and topoisomerase IV (parC). The production of biofilm by these isolates was also examined and the associated medical records were retrospectively reviewed. Seven of 189 (3.7%) strains from uncomplicated UTIs and 82 of 639 (12.8%) strains from complicated UTIs were insusceptible to fluoroquinolones. Amino acid replacements of type II topoisomerases were frequently observed at positions 83 and 87 in GyrA and at positions 80 and 84 in ParC. No significant difference in the biofilm-forming capabilities was observed between fluoroquinolone-susceptible and -insusceptible E. coli. Our study suggests that biofilm formation of fluoroquinolone-insusceptible E. coli isolates is not a major mechanism of resistance in patients with UTI.

In 2000, chlamydial strains OK133 and OK135 were isolated from 2 female patients with cervicitis. These strains were unresponsive to commercially available PCR and LCR test kits for the diagnosis of Chlamydia trachomatis infection, and their phenotypic characteristics were very similar. The OK135 nucleotide sequence in MOMP-VD2 gene closely resembled that of Chlamydophila caviae GPIC. A similar strain was isolated in 2003 from a male patient OKM2 with urethritis, from which the strain SC10-6 was cloned by the plaque purification method. The nucleotide sequence of the entire MOMP gene of SC10-6 was exactly the same as that of OK135. Thus, the strains OK135 and SC10-6, together with OK133, have been called C. caviae-like Chlamydia. We designed primers for nested PCR assay, the product of which showed a single-band 311-bp fragment, to detect C. caviae-like Chlamydia. Of swab specimens obtained from 202 patients from 2003 to 2006 (119 male and 83 female patients), 18 specimens (8.9%) from 14 male and 4 female patients were positive, suggesting that C. caviae-like Chlamydia infection is rather common. Thus far, it has not been determined whether C. caviae-like Chlamydia is pathogenic for humans.

We explored the effectiveness of loxoprofen sodium (loxoprofen), which is the most common non-steroidal anti-inflammatory drug (NSAID) in Japan, for patients with benign prostatic hyperplasia (BPH) complaining of nocturia. A total of 93 BPH patients aged 49-84 years were enrolled in the study. These patients had received standard drug therapy with alpha1-blocker for BPH, followed by anticholinergic drugs, hypnotics, tricyclic antidepressants, and/or antiduretic hormone, but they still complained about 2 or more episodes of nocturia. They each took a single 60-mg tablet of loxoprofen prior to sleeping at night for 14 days in addition to their BPH treatments. The effects were assessed by questionnaire before and after treatment as excellent (nocturia disappeared or decreased by 2 or more voids/night), improved (nocturia decreased by 1 void/night), unchanged, or worsened (nocturia increased). Nocturia improved or disappeared in 74.2% of patients: excellent, improved, unchanged, and worsened results were obtained in 37.6%, 36.6%, 21.5%, and 4.3% of patients, respectively. The effects were better in patients whose baseline nocturia was > 2 times than in those with a lesser frequency at enrollment (P = 0.04). Loxoprofen can be an effective and useful treatment option for patients with BPH complaining of refractory nocturia.

We evaluated the efficiency and toxicity of estramustine phosphate (ECT), ifosfamide (IFM) and cisplatin (CDDP) combination chemotherapy in twenty-one patients with hormone-refractory prostate cancer (HRPC), for which there is currently no effective treatment. Patients received a daily dose of 560 mg ECT in combination with 1.2 g/m2 IFM on days 1 to 5 and 70 mg/m2 CDDP on day 1. This combination therapy was given every 3 to 4 weeks. An objective response of more than 50% reduction in prostate-specific antigen was observed in 9 of 18 patients (50%), and a more than 50% reduction in bi-dimensionally measurable soft-tissue lesions was observed in 2 of 7 patients (29%). The median duration of response among the cases showing partial response was 40 weeks, while the median duration of response of overall partial-response plus stable cases was 30 weeks. The median survival duration of all cases was 47 weeks. Toxicity was modest and acceptable. In conclusion, the ECT, IFM and CDDP combination chemotherapy regimen is a viable treatment option for HRPC. However, in comparison with our previous chemotherapy regimen of IFM and CDDP, no additional long-lasting effects resulting from the inclusion of ECT could be affirmed.

We investigated the usefulness of one-stage urethroplasty by the parameatal foreskin flap method (OUPF procedure), which is useful for repairing all types of hypospadias. Between June 1992 and March 2001, the OUPF procedure was performed on 18 patients with hypospadias: 10 patients with distal and 8 with proximal hypospadias. The follow-up periods ranged from 33-75 months, with an average of 52 months. The duration of surgery, the catheter indwelling period, and the postoperative complications of each patient were analyzed. The median age of the patients at the time of surgery was 3 years and 8 months. The length of surgery for OUPF II ranged from 150-230 min (average 186 min), and from 190-365 min (average 267 min) for OUPF IV. Postoperative complications were confirmed in 3 of the 18 patients (16.6%). Two patients had fistulas, and one had a meatal regression. The fistulas were successfully closed by the simple multilayered closure method. After adopting DuoDerm dressings instead of elastic bandages for protection of the wound, no fistulization occurred. DuoDerm dressings are useful in the healing of wounds without complications. To date, the longest follow-up period has been 75 months, and during that time there have been no late complications such as urethral stenosis or penile curvature. OUPF is a useful method in the treatment of hypospadias with a low incidence of early and late complications.

The potential relationships between biofilm formation and pathogenicity of Enterococcus faecalis in urinary tract infections (UTI) were investigated. Over a 12-year period from 1991 through 2002, a total of 352 E.faecalis isolates were collected from patients with complicated UTI (one isolate per patient) at the urology ward of Okayama University Hospital. We analyzed the prevalence and transferability of genes encoding virulence factors(asa1, esp, cylA, gelE /sprE )and antimicrobial resistance(aac(6') /aph(2'')). The production of biofilm, hemolysin and gelatinase by these isolates was also examined and the associated medical records of patients were retrospectively reviewed. Of 352 E. faecalis isolates, 315 possessed and/or genes. Of the 63 hemolysin- and 167 gelatinase-producing isolates, 59 and 94 isolates, respectively, possessed both asa1 and esp genes. E. faecalis isolates with both asa1 and esp genes formed biofilms at significantly higher rates than those with neither gene (P=0.038). The genes encoding asa1, cylA , and aac(6') /(aph(2'') were transferable and appeared to have accumulated in these isolates. The E. faecalis isolates possessing asa1 and/or esp genes were found from both catheter-related or -unrelated UTI. Our study indicates that E. faecalis isolates that have accumulated virulence genes are apt to form persistent biofilms in the urinary tracts.