Hideyasu Tsumura

Prevalence of Fluoroquinolone-resistant Escherichia coli Before and Incidence of Acute Bacterial Prostatitis After Prostate Biopsy

OBJECTIVE To study the prevalence of fluoroquinolone-resistant Escherichia coli before transrectal ultrasound (TRUS)-guided prostate biopsy and prospectively analyze the rates of infective complications after biopsy in patients receiving fluoroquinolone prophylaxis. E. coli is the pathogen most commonly associated with infections after TRUS-guided prostate biopsy, and the prevalence of fluoroquinolone-resistant E. coli is increasing. METHODS We analyzed the prospective data from 100 patients who underwent TRUS-guided prostate biopsy from April to December 2010. A stool culture was obtained 1 month before biopsy. Patients received 500 mg levofloxacin orally once daily for 3 days, beginning 2 hours before biopsy. All biopsies were performed as outpatient procedures. RESULTS Of the 100 patients, 13 (13%) had a stool culture positive for fluoroquinolone-resistant E. coli. In 4 (31%) of these 13 patients, acute bacterial prostatitis was detected after TRUS-guided prostate biopsy. Of the 87 patients whose stool culture was negative for fluoroquinolone-resistant E. coli, none had acute bacterial prostatitis. All 13 infected patients were treated with carbapenems immediately after diagnosis of prostatitis and made a complete recovery. CONCLUSION Prophylactic fluoroquinolone is still effective in preventing acute bacterial prostatitis after TRUS-guided prostate biopsy. The incidence is relatively low in patients with fluoroquinolone-sensitive E. coli. However, the prevalence of fluoroquinolone-resistant E. coli is about 13% in this population. Stool cultures for the detection of fluoroquinolone-resistant E. coli might be obtained before TRUS-guided prostate biopsy.

Prostate-specific antigen ‘bounce’ after permanent 125I-implant brachytherapy in Japanese men: a multi-institutional pooled analysis

To examine the incidence, timing, and magnitude of the prostate‐specific antigen (PSA) level ‘bounce’ after permanent prostate brachytherapy (BT) and correlate the PSA bounce with clinical and dosimetric factors in Japanese patients with prostate cancer.

Radiotherapy for oligometastases and oligo-recurrence of bone in prostate cancer.

Purpose. To retrospectively evaluate the clinical significance of radiotherapy for oligometastases of bone in prostate cancer (PCa). Methods and Materials. Between 2003 and 2008, 35 PCa patients with oligometastases of bone were treated with radiotherapy. Results. The median radiotherapy dose was 40 Gy. The 3-year overall survival rates for all patients, for patients that received a radiotherapy dose of ≥40 Gy (n = 21) and for those that received <40 Gy (n = 14), were 77.2%, 90.5%, and 50.0%, respectively. Fourteen out of 16 patients (87.5%) who had pain were improved 1 month after radiotherapy. The median duration of pain relief was 12 months. Pathological fracture and spinal cord compression (SCC) were not seen at the treated sites but developed at nonirradiated sites in three patients (8.6%) and in one patient (2.8%), respectively. Although the high-dose group (≥40 Gy) achieved better survival than the low-dose group (<40 Gy), it was not independent prognostic factor in multivariable analysis. Conclusions. Radiotherapy of bone oligometastases in PCa was effective for long-term pain relief. Pathological fracture and SCC were not seen at the treated sites. A larger clinical trial is warranted to study the actual benefit following radiotherapy for oligometastases of bone in PCa.

Comparison of Prophylactic Naftopidil, Tamsulosin, and Silodosin for 125I Brachytherapy–Induced Lower Urinary Tract Symptoms in Patients With Prostate Cancer: Randomized Controlled Trial

PURPOSE To compare the efficacy of three α(1A)/α(1D)-adrenoceptor (AR) antagonists--naftopidil, tamsulosin, and silodosin--that have differing affinities for the α(1)-AR subtypes in treating urinary morbidities in Japanese men with (125)I prostate implantation (PI) for prostate cancer. METHODS AND MATERIALS This single-institution prospective randomized controlled trial compared naftopidil, tamsulosin, and silodosin in patients undergoing PI. Patients were randomized and received either naftopidil, tamsulosin, or silodosin. Treatment began 1 day after PI and continued for 1 year. The primary efficacy variables were the changes in total International Prostate Symptom Score (IPSS) and postvoid residual urine (PVR). The secondary efficacy variables were changes in IPSS storage score and IPSS voiding score from baseline to set points during the study (1, 3, 6, and 12 months). RESULTS Two hundred twelve patients were evaluated in this study between June 2006 and February 2009: 71, 70, and 71 patients in the naftopidil, tamsulosin, and silodosin groups, respectively. With respect to the primary efficacy variables, the mean changes in the total IPSS at 1 month after PI in the naftopidil, tamsulosin, and silodosin groups were +10.3, +8.9, and +7.5, respectively. There were significantly greater decreases with silodosin than naftopidil at 1 month in the total IPSS. The mean changes in the PVR at 6 months were +14.6, +23.7, and +5.7 mL in the naftopidil, tamsulosin, and silodosin groups, respectively; silodosin showed a significant improvement in the PVR at 6 months vs. tamsulosin. With respect to the secondary efficacy variables, the mean changes in the IPSS voiding score at 1 month in the naftopidil, tamsulosin, and silodosin groups were +6.5, +5.6, and +4.5, respectively; silodosin showed a significant improvement in the IPSS voiding score at 1 month vs. naftopidil. CONCLUSIONS Silodosin has a greater impact on improving PI-induced lower urinary tract symptoms than the other two agents.

A Prospective Quasi-Randomized Comparison of Intraoperatively Built Custom-Linked Seeds Versus Loose Seeds for Prostate Brachytherapy

PURPOSE To compare dosimetric parameters, seed migration rates, operation times, and acute toxicities of intraoperatively built custom-linked (IBCL) seeds with those of loose seeds for prostate brachytherapy. METHODS AND MATERIALS Participants were 140 patients with low or intermediate prostate cancer prospectively allocated to an IBCL seed group (n=74) or a loose seed group (n=66), using quasirandomization (allocated by week of the month). All patients underwent prostate brachytherapy using an interactive plan technique. Computed tomography and plain radiography were performed the next day and 1 month after brachytherapy. The primary endpoint was detection of a 5% difference in dose to 90% of prostate volume on postimplant computed tomography 1 month after treatment. Seed migration was defined as a seed position >1 cm from the cluster of other seeds on radiography. A seed dropped into the seminal vesicle was also defined as a migrated seed. RESULTS Dosimetric parameters including the primary endpoint did not differ significantly between groups, but seed migration rate was significantly lower in the IBCL seed group (0%) than in the loose seed group (55%; P<.001). Mean operation time was slightly but significantly longer in the IBCL seed group (57 min) than in the loose seed group (50 min; P<.001). No significant differences in acute toxicities were seen between groups (median follow-up, 9 months). CONCLUSIONS This prospective quasirandomized control trial showed no dosimetric differences between IBCL seed and loose seed groups. However, a strong trend toward decreased postimplant seed migration was shown in the IBCL seed group.

Four-year experience of interstitial permanent brachytherapy for Japanese men with localized prostate cancer.

OBJECTIVE To report 4 year results obtained with our initial 100 patients with localized prostate cancer treated by interstitial permanent brachytherapy. METHODS One-hundred Japanese men with clinically localized prostate cancer underwent interstitial permanent prostate brachytherapy using (125)I seeds. Median follow-up was 36 months (range, 30-42 months). Median initial prostate-specific antigen (PSA) level was 6.7 ng/ml (range, 1.5-25.2 ng/ml). Of these 100 patients, 31 received neoadjuvant hormone therapy for several months. Treatment morbidities were assessed using Radiation Therapy Oncology Group (RTOG) scale and National Cancer Institute Common Toxicity Criteria. RESULTS A mean of 95 seeds (range, 48-123 seeds) were successfully implanted in patients with prostate cancer. Mean prostate volume receiving at least 100% dose (V100) and dose to 90% of prostate volume (D90) for the 100 patients were 96.6% and 166.1 Gy, respectively. Urinary morbidity was common, but was usually not severe. Only four patients needed catheterization for urinary retention (Grade 3) during follow-up. Most patients displayed no rectal morbidity after implantation, with only 3% of patients showing RTOG Grade 2 rectal morbidity and no patients showing morbidity of Grade 3 or more. Three patients experienced biochemical failure according to Phoenix consensus definition during follow-up. One patient displayed clinical failure with lymph node recurrence. CONCLUSIONS These results indicate that interstitial permanent brachytherapy is safe and effective for Japanese patients with localized prostate cancer. The import of matured techniques developed in Western countries might allow bypass of the trial-and-error process in Japanese institutions.

125Iodine monotherapy for Japanese men with low- and intermediate-risk prostate cancer: outcomes after 5 years of follow-up

Data from 305 Japanese men with low-risk (n = 175) or intermediate-risk (n = 130) prostate cancer who underwent 125I monotherapy were retrospectively analyzed. Of the 305 patients, 93 received hormonal therapy for a median of 6 months (range, 1–33 months) before implantation. The prescribed dose to the prostate plus 3- to 5-mm margin was set at 145 Gy. The mean dose to 90% of the prostate volume at 1 month (D90) and the prostate volume receiving at least 100% dose at 1 month (V100) were 173.4 Gy and 95.8%, respectively. The median follow-up was 66 months (range, 12–94 months). The 5-year biochemical non-evidence of disease rate was 95.5% (low-risk, 94.2%; intermediate-risk, 97.3%). The 5-year freedom from clinical failure rate was 98.9% (low-risk, 98.9%; intermediate-risk, 99.2%).The initial prostate-specific antigen level was identified as a significant predictive factor for biochemical recurrence (P = 0.029). The late Grade 3 genitourinary toxicity rate was 2.0%. No patients displayed late gastrointestinal toxicity of Grade 3 or worse. Monotherapy with 125I showed excellent outcomes with limited morbidity for Japanese men with low- and intermediate-risk prostate cancer after 5 years of follow-up.

Recovery of serum testosterone following neoadjuvant and adjuvant androgen deprivation therapy in men treated with prostate brachytherapy

AIM To investigate the time course of testosterone (T) recovery after cessation of androgen deprivation therapy (ADT) in patients treated with brachytherapy. METHODS One-hundred and seventy-four patients treated between June 1999 and February 2009 were studied. Patients were divided into a short-term usage group (≤ 12 mo, n = 91) and a long-term usage group (≥ 36 mo, n = 83) according to the duration of gonadotropin-releasing hormone agonist therapy. Median follow-up was 29 mo in the short-term group and was 60 mo in the long-term group. RESULTS Cumulative incidence rates of T recovery to normal and supracastrate levels at 24 mo after cessation were 28.8% and 74.6%, respectively, in the long-term usage group, whereas these values were 96.4% and 98.8% in the short-term usage group. T recovery to normal and supracastrate levels occurred significantly more rapidly in the short-term than in the long-term usage group (P < 0.001 and P < 0.001, respectively). Five years after cessation, 22.6% of patients maintained a castrate T level in the long-term usage group. On multivariate analysis, lower T levels (< 10 ng/dL) at cessation of ADT was significantly associated with prolonged T recovery to supracastrate levels in the long-term usage group (P = 0.002). CONCLUSION Lower T levels at cessation of ADT were associated with prolonged T recovery in the long-term usage group. Five years after cessation of long-term ADT, approximately one-fifth of patients still had castrate T levels. When determining the therapeutic effect, especially biochemical control, we should consider this delay in T recovery.

Dosimetry of permanent interstitial prostate brachytherapy for an interoperative procedure, using O-arm based CT and TRUS

Purpose The aim of this report is dosimetric evaluation for an intraoperative fusion computed tomography (CT) as a superior predictor of 1-month CT based dosimetry in comparison to transrectal ultrasound (TRUS) in permanent interstitial prostate brachytherapy. Material and methods Data of 65 patients treated with seed implantation were analyzed. All procedures has been performed with patients in the lithotomy position inside the O-arm system. An end-fine probe is used as a landmark to fuse TRUS and O-arm-based CT images. There was no difference in the patients position, probe position, and timing of image acquisition between the two imaging modalities. Dose-volume histogram (DVH) parameters such as the dose to 90% of prostate volume (D90) has been analyzed. Results The area under the curve of the receiver operating characteristic tended to be larger on fusion CT than on TRUS for most DVH parameters (71.85% vs. 59.59% for D90; p = 0.07). Significant relationships between fusion CT and 1-month CT were confirmed using Pearsons correlation coefficients for most DVH parameters (R = 0.48, p < 0.01 for D90), although the relationship between TRUS and 1-month CT was poor. Large dose reduction (35 Gy for D90) was seen from TRUS to fusion CT, especially in patients with high body weight and small prostate volume. Conclusions Intraoperative fusion CT appears to have higher predictive power for 1-month CT-based dosimetry than TRUS. A prospective trial using fusion CT-based planning is warranted.

High expression level of preoperative serum Uroplakin III is associated with biologically aggressive bladder cancer.

BACKGROUND Uroplakins have been widely investigated as potential markers in patients with bladder cancer because these proteins are specific to the urothelium. However, the role of uroplakin proteins in bladder cancer remains unknown. In this study, preoperative serum levels of uroplakin III were measured in patients with urothelial carcinoma of the urinary bladder and examined for possible association with clinicopathological features and clinical outcomes. MATERIALS AND METHODS This study included 52 bladder cancer patients at various stages and 28 healthy controls. Uroplakin III levels were detected in preoperative sera using an automated dot blot system and a micro-dot blot array. RESULTS There was a significant increase in serum uroplakin III levels in patients with bladder cancer as compared to healthy controls (p<0.05). In addition, serum uroplakin III levels were associated with muscle-invasive status, high grade and lymphovascular invasion (p<0.02). Log-rank tests indicated high serum uroplakin III to be significantly associated with cancer-specific mortality. CONCLUSIONS Determination of serum uroplakin III level could be valuable for identifying patients with biologically aggressive bladder cancer.