Hisanobu Adachi

Identification of thyroid hormone transporters in humans: different molecules are involved in a tissue-specific manner.

We have recently identified that rat organic anion transporters, polypeptide2 (oatp2) and oatp3, both of which transport thyroid hormones. However, in humans the molecular organization of the organic anion transporters has diverged, and the responsible molecule for thyroid hormone transport has not been clarified, except for human liver-specific transporter (LST-1) identified by us. In this study we isolated and characterized a novel human organic anion transporter, OATP-E from human brain. The isolated complementary DNA encodes a polypeptide of 722 amino acids with 12 transmembrane domains. A rat counterpart, oatp-E, was also identified. Homology analysis and the phylogenetic tree analysis revealed that OATP-E/oatp-E is a subfamily of the organic anion transporter. Human OATP-E transported 3,3′,5-triiodo-l-thyronine (Km, 0.9μ m), thyronine, and rT3 in a Na+-independent manner. Although the clone was isolated from the brain, OATP-E messenger RNA was abundantly expressed in various peripheral tissues. The ...

Prospective Randomized Phase II Trial of a Single Early Intravesical Instillation of Pirarubicin (THP) in the Prevention of Bladder Recurrence After Nephroureterectomy for Upper Urinary Tract Urothelial Carcinoma: The THP Monotherapy Study Group Trial

PURPOSE We evaluated the efficacy of a single early intravesical instillation of pirarubicin (THP) in the prevention of bladder recurrence after nephroureterectomy for upper urinary tract urothelial carcinoma (UUT-UC). PATIENTS AND METHODS From December 2005 to November 2008, 77 patients clinically diagnosed with UUT-UC from 11 institutions participating in the Tohoku Urological Evidence-Based Medicine Study Group were preoperatively enrolled in this study. Patients were randomly assigned to receive or not receive a single instillation of THP (30 mg in 30 mL of saline) into the bladder within 48 hours after nephroureterectomy. Cystoscopy and urinary cytology were repeated every 3 months for 2 years or until the occurrence of first bladder recurrence. RESULTS Seventy-two patients were evaluable for efficacy analysis, 21 of whom had a subsequent bladder recurrence. Significantly fewer patients who received THP had a recurrence compared with the control group (16.9% at 1 year and 16.9% at 2 years in the THP group v 31.8% at 1 year and 42.2% at 2 years in the control group; log-rank P = .025). No remarkable adverse events were observed in the THP-treated group. Based on multivariate analysis, THP instillation (hazard rate [HR], 0.26; 95% CI, 0.07 to 0.91; P = .035) and open surgery (HR, 0.28; 95% CI, 0.09 to 0.84; P = .024) were independently predictive of a reduced incidence of bladder recurrence. CONCLUSION In this prospective randomized phase II study, a single intravesical instillation of THP seemed to reduce bladder recurrence after nephroureterectomy. A phase III, large-scale, multicenter study is needed to confirm these observations.

Intravesical Seeding of Upper Urinary Tract Urothelial Carcinoma Cells During Nephroureterectomy: An Exploratory Analysis from the THPMG Trial

OBJECTIVE The Pirarubicin Monotherapy Study Group trial was a randomized Phase II study that evaluated the efficacy of intravesical instillation of pirarubicin in the prevention of bladder recurrence after nephroureterectomy for upper urinary tract urothelial carcinoma. This study conducted further analysis of the Pirarubicin Monotherapy Study Group cohort, focusing on intravesical seeding of cancer cells. METHODS Using the data from the Pirarubicin Monotherapy Study Group trial, bladder recurrence-free survival rates and factors associated with bladder recurrence in the control group were analyzed. RESULTS Of 36 patients in the control group, 14 with positive urine cytology had more frequent recurrence when compared with the 22 patients with negative cytology (P = 0.004). Based on the multivariate analysis in the control group, voided urine cytology was an independent predictive factor of bladder recurrence (hazard ratio, 5.54; 95% confidence interval 1.12-27.5; P = 0.036). Of 72 patients in the Pirarubicin Monotherapy Study Group trial, 31 had positive urine cytology. Among the 31 patients, 17 patients who received pirarubicin instillation had fewer recurrences when compared with 14 patients who received control treatment (P = 0.0001). On multivariate analysis, pirarubicin instillation was an independent predictor of better recurrence-free survival rates in the patients with positive urine cytology (hazard ratio, 0.02; 95% confidence interval, 0.00-0.53; P = 0.018). Of 21 patients with bladder recurrence, 17 had recurrent tumor around cystotomy or in the bladder neck compromised by the urethral catheter, supporting the notion that tumor cells seeded in the injured urothelium. CONCLUSIONS Intravesical instillation of pirarubicin immediately after nephroureterectomy significantly reduced the bladder recurrence rate in patients with positive voided urine cytology. The results suggest that intravesical seeding of upper urinary tract urothelial carcinoma occurs during nephroureterectomy.

Urinary straining contributes to inguinal hernia after radical retropubic prostatectomy

To verify whether abdominal pressure during urination represents an important factor in the postoperative development of inguinal hernia after radical retropubic prostatectomy.

Serum luteinizing hormone concentration is significantly associated with recovery of urinary function after radical prostatectomy

To perform a longitudinal investigation of the correlation between functional recovery and sex hormone concentrations after radical prostatectomy (RP).

Clinical predictors of the estimated glomerular filtration rate 1 year after radical nephrectomy in Japanese patients

Purpose To evaluate renal function 1 year after radical nephrectomy (RN) for renal cell carcinoma, the preoperative predictors of postnephrectomy renal function were investigated by sex, and equations to predict the estimated glomerular filtration rate (eGFR) 1 year after RN were developed. Materials and Methods A total of 525 patients who underwent RN between May 2007 and August 2011 at Tohoku University Hospital and its affiliated hospitals were prospectively evaluated. Overall, 422 patients were analyzed in this study. Results Independent preoperative factors associated with postnephrectomy renal function were different in males and females. Preoperative eGFR, age, tumor size, and body mass index (BMI) were independent factors in males, while tumor size and BMI were not independent factors in females. The equations developed to predict eGFR 1 year after RN were: Predicted eGFR in males (mL/min/1.73 m2)=27.99−(0.196×age)+(0.497×eGFR)+(0.744×tumor size)−(0.339×BMI); and predicted eGFR in females=44.57−(0.275×age)+(0.298×eGFR). The equations were validated in the validation dataset (R2=0.63, p<0.0001 and R2=0.31, p<0.0001, respectively). Conclusions The developed equations by sex enable better prediction of eGFR 1 year after RN. The equations will be useful for preoperative patient counseling and selection of the type of surgical procedure in elective partial or RN cases.

Phosphodiesterase type 5 inhibitor administered immediately after radical prostatectomy temporarily increases the need for incontinence pads, but improves final continence status

Purpose To evaluate the effects of phosphodiesterase type 5 inhibitor (PDE5i) on urinary continence recovery after bilateral nerve-sparing radical prostatectomy (BNSRP). Materials and Methods Between 2002 and 2012, 137 of 154 consecutive patients who underwent BNSRP in our institution retrospectively divided into 3 groups that included patients taking PDE5i immediately after surgery (immediate PDE5i group, n=41), patients starting PDE5i at an outpatient clinic after discharge (PDE5i group, n=56), and patients taking no medication (non-PDE5i group, n=40). Using self-administered questionnaires, the proportion of patients who did not require incontinence pads (pad-free patients) was calculated preoperatively and at 1, 3, 6, 12, 18, and 24 months after BNSRP. Severity of incontinence was determined based on the pad numbers and then compared among the 3 groups. Results Proportions of pad-free patients and severity of incontinence initially deteriorated in all of the groups to the lowest values soon after undergoing BNSRP, with gradual improvement noted thereafter. The deterioration was most prominent in the immediate PDE5i group. As compared to the non-PDE5i group, both the PDE5i and immediate PDE5i groups exhibited a better final continence status. Conclusions PDE5i improves final continence status. However, administration of PDE5i immediately after surgery causes a distinct temporary deterioration in urinary incontinence.

MP37-19 SHORT-TERM IMPACT ON HEALTH-RELATED QUALITY OF LIFE OF LAPAROSCOPIC ADRENALECTOMY FOR PRIMARY ALDOSTERONISM IN JAPANESE PATIENTS

INTRODUCTION AND OBJECTIVES: Primary aldosteronism (PA) is one of the typical forms of secondary hypertension (HTN). Our previous study showed that the antihypertensive effect of laparoscopic adrenalectomy (LA) was not a little for elderly PA patients suffering from HTN for many years. However, the impact of LA on health-related quality of life (QOL) in those patients has not been evaluated. METHODS: According to Japanese diagnostic criteria for PA, a total of 178 PA patients who underwent LA between July 2012 and December 2015 were eligible for this study. Demographic data, perioperative outcomes and QOL were examined. QOL was assessed using the Short Form 36-Item Health Survey questionnaire before and at 6, 12, 18 and 24 months after LA. RESULTS: Responses were analyzed for 96 of 136 patients (70.6%) who responded to the questionnaire. Median age was 55 years (range, 25-77 years) andmedianduration ofHTNwas9 years (range, 1-43 years). Median follow-up was 12months (range, 6-24months) after LA. To evaluate the influence of the duration of HTN on health-related QOL, we compared differences in Norm-based Scoring in Japanese between patients with HTN for <10 years (median age, 51 years) and patients with HTN >10 years (median age, 60 years). In the former group, scores improved in all 8 health-related QOL domains from the baseline at the 6month survey after LA (Figure A). In the latter group, scores of 4 domains did not improve in terms of Physical functioning, Bodily pain, Social functioning or Mental health. However, scores for another 4 domains improved from the baseline (Figure B). Furthermore no significant differences between groups were evident 6 months after LA in any domains scores. CONCLUSIONS: To the best of our knowledge, normalizing aldosterone levels by LA contributes not only to antihypertensive effect, but also to protective effects against cardiovascular diseases. In our study, LA for PA patients with short-term HTN leads to much greater improvements in prognosis and QOL. However, improvements of QOL by LA was found among PA patients despite long-term use of HTN. The negative impact of LA for PA patients with long-term HTN on Social functioning and Mental health remains to be elucidated. More time is needed to evaluate the influence of LA on long-term QOL among PA patients with long-term HTN to achieve better outcomes from LA.

MP80-02 INCREASING AGE OF PATIENTS WITH TESTICULAR CANCER: 1980-2016 SINGLE-CENTER EXPERIENCE

INTRODUCTION AND OBJECTIVES: Local recurrence rate of penile cancer following surgical excision is reported in many series to be between 6 and-29%. Intra-operative Frozen Section (FS) is a useful tool to ensure safe microscopic margins in organ sparing procedures in penile cancer. In this series, we evaluated the impact of intra-operative surgical margin assessment by FS examination during penile-cancer preserving surgery on the local recurrence rate. METHODS: We analysed all those patients in which intraoperative FS was employed during penile preserving surgery in a single tertiary referral centre (catchment of 6.5 million) from 2007-2014. The tissue analysed for margins was the Urethral “donut”, corporal and/or glandular tissue proximal to the resection margin. We looked to see if this technique altered the surgical technique and what affect it had on recurrence rates. Median follow-up was 28 (1-114) months. RESULTS: Of the total number of 93 patients, 39 (41.9%) had a total glansectomy, 44 (47.3%) a partial penectomy, 7 (7.5%) a wide local excision, 2 (2.2%) a total penectomy and one (1%) a circumcision. Intra-operative histological FS examination of the surgical margin was positive in 16 (17.2%) cases mandating further resection under the same anaesthetic. Final paraffin histological examination confirmed cancer-free margins in 100%. At follow-up, none of the 16 patients with initial positive FS had local recurrence. Only 1 (1%) patient with negative intra-operative FS developed local recurrence at 23 months. This patient’s histology was initially G3pT4. CONCLUSIONS: The use of intra-operative frozen section analysis during organ preserving surgery for penile cancer facilitates conservative surgery, reduces the need, distress and expense of further surgery and in this series contributed to a very low rate (1%) of local recurrence.

MP86-07 IMPACT OF TISSUE SEALING SHEET ON ERECTILE DYSFUNCTION IN A RAT MODEL OF NERVE-SPARING RADICAL PROSTATECTOMY

INTRODUCTION AND OBJECTIVES: We investigated combined therapeutic efficacy of human adipose-derived stem cells (h-ADSCs) application on injured cavernous nerve and low-energy shockwave therapy (SWT) on the corpus cavernosum in a rat model of post-prostatectomy erectile dysfunction. METHODS: Rats were randomly divided into five groups: Control, BCNI (bilateral cavernous nerve injury), ADSC (BCNI group with h-ADSCs on the cavernous nerve), SWT (BCNI group with lowenergy SWT on the corpus cavernosum), and ADSC/SWT (BCNI group with a combination of h-ADSCs and low-energy SWT). After four weeks, erectile function was assessed using intracavernosal pressure (ICP). The cavernous nerves and penile tissue were evaluated through immunostaining, western blotting and a cyclic guanosine monophosphate (cGMP) assay. RESULTS: ADSC/SWT significantly improved ICP compared to the other experimental group. ADSC had significantly increased s-III tubulin expression of cavernous nerve, and SWT had markedly enhanced vascular endothelial growth factor (VEGF) expression in corpus cavernosum. The ADSC/SWT group had a significantly increased in alpha smooth muscle content (P <.05), neural nitric oxide synthase (nNOS) of the dorsal penile nerve (P <.05), endothelial nitric oxide synthase (eNOS) protein expression (P <.05), and cGMP level (P <.05) compared to ADSC or SWT alone group. In addition, ADSC/SWT reduces the apoptotic index in corpus cavernosum. CONCLUSIONS: In this study, h-ADSCs showed effect on recovery of injured cavernous nerve and low-energy SWT improved angiogenesis in the corpus cavernosum. The h-ADSCs combined with low energy SWT showed beneficial effect on the recovery of erectile function in a rat model of post-prostatectomy erectile dysfunction.