Motoo Araki

Nerve growth factor level in the prostatic fluid of patients with chronic prostatitis/chronic pelvic pain syndrome is correlated with symptom severity and response to treatment

Study Type – Therapy (case series)

Robot-assisted laparoscopic radical prostatectomy in the Asian population: Modified port configuration and ultradissection

We have carried out over 360 cases of robot‐assisted laparoscopic radical prostatectomy (RARP) to date. In the present study, we detail our current technique at Yonsei University College of Medicine. The six‐port transperitoneal approach is utilized. The most lateral two ports were placed medially and caudally in patients with a small pelvis to avoid interference between the ports and the pelvis (modified port configuration). Lymph node dissection is carried out in the external iliac, obturator and infraobturator area. The dissection on the lateral border of the bladder neck is carried out until it reaches the seminal vesicle (ultradissection). After transection of the bladder neck, vasa seminal vesicles are dissected further. Neurovascular bundles are preserved in selected patients. The dorsal venous complex (DVC) and the urethra are transected without suturing. Urethrovesical anastomosis is carried out with 3‐0 monocryl running suture, incorporating with the edge of DVC. The puboprostatic collar and bladder are incorporated by 3‐0 monocryl running suture (puboperineoplasty). Between November 2007 and September 2008, RARP was carried out using this technique in 182 patients. Median height, weight, body mass index and prostate‐specific antigen (PSA) were 168 cm, 68 kg, 24 kg/M2 and 7.1 ng/mL, respectively. Mean operative time was 192 min and average blood loss was 250 mL. Median catheterization time was 8 days. Positive surgical margin rates for pT2, pT3 and pT4 disease was 12.7, 48 and 100%, respectively. Intraoperative complication rate was 2.7%. Fifty‐five patients completed a minimum of 10 months follow up. Their continence rate was 91%. RARP is a safe and feasible surgical modality for prostate cancer among Asian patients with a small pelvis. Our technique achieves a precise bladder neck dissection.

Adenovirus vector carrying REIC/DKK-3 gene: neoadjuvant intraprostatic injection for high-risk localized prostate cancer undergoing radical prostatectomy

As the First-In-Human study of in situ gene therapy using an adenovirus vector carrying the human REIC (reduced expression in immortalized cell)/Dkk-3 gene (Ad-REIC), we conducted neoadjuvant intraprostatic injections in patients with high-risk localized prostate cancer undergoing radical prostatectomy (RP). Patients with recurrence probability of 35% or more within 5 years following RP, as calculated by Kattan’s nomogram, were enrolled. Patients received two ultrasound-guided intratumoral injections at 2-week intervals, followed by RP 6 weeks after the second injection. After confirming the safety of the therapeutic interventions with initially planned three escalating doses of 1.0 × 1010, 1.0 × 1011 and 1.0 × 1012 viral particles (vp) in 1.0–1.2 ml (n=3, 3 and 6), an additional higher dose of 3.0 × 1012 vp in 3.6 ml (n=6) was further studied. All four DLs including the additional dose level-4 (DL-4) were feasible with no adverse events, except for grade 1 or 2 transient fever. Laboratory toxicities were grade 1 or 2 elevated aspartate transaminase/alanine transaminase (n=4). Regarding antitumor activities, cytopathic effects (tumor degeneration with cytolysis and pyknosis) and remarkable tumor-infiltrating lymphocytes in the targeted tumor areas were detected in a clear dose-dependent manner. Consequently, biochemical recurrence-free survival in DL-4 was significantly more favorable than in patient groups DL-1+2+3.

Ureteroscopic management of chronic unilateral hematuria: a single-center experience over 22 years.

Objective To analyze the short and long term safety and efficacy of ureteroscopic evaluation and management of chronic unilateral hematuria. Methods We retrospectively reviewed patients with chronic unilateral hematuria from 1987 to 2008. The distal to middle ureter was evaluated with a semi-rigid ureteroscope without a guidewire. Subsequently, the flexible ureteroscope was advanced into the upper ureter to the renal pelvis using a low-pressure automated irrigant system (Uromat™). Lesions identified ureteroscopically were treated with diathermy fulguration. Results One hundred and four (56 male, 48 female) patients were identified, with a median age of 37 (14–80) years and median follow-up of 139 (34–277) months. The median preoperative duration of gross hematuria was 5 (1–144) months. Endoscopic findings included 61 (56%) minute venous rupture (MVR; a venous bleeding without clear abnormalities), 21 (20%) hemangioma (vascular tumor-like structure), 3 (3%) varix (tortuous vein), 1 (1%) calculus and 18 (17%) no lesions. The incidence of “no lesions” was less in the recent 12 years (9%) than the first 10 years (27%), while the incidence of MVR increased from 40 to 66% (p<0.05). All patients were treated endoscopically. Immediate success rate was 96% (100% in the recent 12 years). Long-term recurrent gross hematuria rate was 7%. Six resolved spontaneously and only 1 required ureteroscopy, revealing a different bleeding site. Conclusion Ureteroscopy and diathermy fulguration is highly useful for evaluation and treatment of chronic unilateral hematuria. Sophisticated technique and improved instrumentation contributes to a better outcome.

Detection and isolation of nanobacteria-like particles from urinary stones: long-withheld data.

Objectives:  To report our experimental results on detection and isolation of nanobacteria‐like particles (NLP) from urinary stone samples.

Continence outcomes after bladder neck preservation during robot-assisted laparoscopic prostatectomy (RALP)

Abstract Purpose: Urinary incontinence is one of the major prostate cancer treatment-related morbidities. We review our initial robot-assisted laparoscopic prostatectomy (RALP) experience, focusing on post-surgery continence rates. Material and methods: Two-hundred and thirty-three consecutive patients were identified from a prospectively maintained RALP database. A bladder neck sparing dissection was preferentially performed during transperitoneal RALP. On postoperative day 5 or 6 (clinic logistics), the urethral catheter was removed following a normal cystogram. Results: Median operative time was 190 minutes and estimated blood loss was 75 mL. Three (1.3%) patients required bladder neck reconstruction, while 198 (85.0%) had bilateral, 20 (8.6%) had unilateral and 15 (6.4%) did not undergo nerve sparing prostatectomy. One-hundred and ninety-nine (85.4%) patients had negative surgical margins. Median hospitalization and urethral catheter duration were 1.0 and 5.0 days, respectively. At six weeks, a median 1.0 pad per day usage was reported and mean AUASS and QoL were significantly improved from baseline (p < 0.05). Of the 220 patients having a minimum three-month follow-up, 152 (69.1%) achieved urinary continence without pads. Age, AUASS, QoL, prostate volume and prior TUR surgery independently had significant impact on early continence rate (p < 0.05). Conclusion: A bladder neck sparing dissection allows for early return of urinary continence following RALP without compromising cancer control.

The clinical impact of pathological review on selection the treatment modality for localized prostate cancer in candidates for brachytherapy monotherapy

AimTo evaluate the impact of pathological review by pathologist with genitourinary expertise (PGU) on treatment modality of localized prostate cancer, we analyzed Gleason grade (GG) migration and the final treatment decision in a cohort of patients designated for permanent prostate brachytherapy (PPB).MethodsFrom February 2005 to July 2010, a total of 247 patients with localized prostate cancer diagnosed by local community hospitals were referred to our hospital for PPB monotheray. All pathologic slides of prostate biopsies were reviewed by a single PGU. Patients ultimately selected their treatment modality from our recommendations based on the review. Indication for PPB monotherapy was the NCCN classification of patients as good or intermediate risk. In addition, patient with Primary GG 4 was regarded as unadapted case.ResultsSix cases were reinterpreted as no cancer (2.4%). GG change occurred in 94 cases (38.1%) of which 77 (81.9%) were upgraded and 17 (18.1%) downgraded. Of the total 247 patients, 86 (34.8%) changed therapies and 30 (12.1%) did so based on the pathologic slide review.ConclusionsPathological review of biopsy specimens is mandatory for the determination of treatment modality especially in candidates for monotherapy of permanent prostate brachytherapy.

Feasibility of Neoadjuvant Ad-REIC Gene Therapy in Patients with High-Risk Localized Prostate Cancer Undergoing Radical Prostatectomy.

In a phase I/IIa study of in situ gene therapy using an adenovirus vector carrying the human REIC/Dkk‐3 gene (Ad‐REIC), we assessed the inhibitory effects of cancer recurrence after radical prostatectomy (RP), in patients with high risk localized prostate cancer (PCa). After completing the therapeutic interventions with initially planned three escalating doses of 1.0 × 1010, 1.0 × 1011, and 1.0 × 1012 viral particles (VP) in 1.0–1.2 mL (n = 3, 3, and 6), an additional higher dose of 3.0 × 1012 VP in 3.6 mL (n = 6) was further studied. Patients with recurrence probability of 35% or more within 5 years after RP as calculated by Kattans nomogram, were enrolled. They received two ultrasound‐guided intratumoral injections at 2‐week intervals, followed by RP 6 weeks after the second injection. Based on the findings of MRI and biopsy mapping, as a rule, one track injection to the most prominent cancer area was given to initial 12 patients and 3 track injections to multiple cancer areas in additional 6 patients. As compared to the former group, biochemical recurrence‐free survival of the latter showed a significantly favorable outcome. Neoadjuvant Ad‐REIC, mediating simultaneous induction of cancer selective apoptosis and augmentation of antitumor immunity, is a feasible approach in preventing cancer recurrence after RP. (199)

Predictive factors for acute and late urinary toxicity after permanent interstitial brachytherapy in Japanese patients

To describe the frequency of and to determine predictive factors associated with Radiation Therapy Oncology Group urinary toxicity in prostate brachytherapy patients.

Synergistic effects of the immune checkpoint inhibitor CTLA-4 combined with the growth inhibitor lycorine in a mouse model of renal cell carcinoma

Renal cell carcinoma (RCC) management has undergone a major transformation over the past decade; immune checkpoint inhibitors are currently undergoing clinical trials and show promising results. However, the effectiveness of immune checkpoint inhibitors in patients with metastatic RCC (mRCC) is still limited. Lycorine, an alkaloid extracted from plants of the Amaryllidaceae family, is touted as a potential anti-cancer drug because of its demonstrative growth inhibition capacity (induction of cell cycle arrest and inhibition of vasculogenic mimicry formation). Moreover, T cell checkpoint blockade therapy with antibodies targeting cytotoxic T-lymphocyte associated protein 4 (CTLA-4) has improved outcomes in cancer patients. However, the anti-tumor efficacy of combined lycorine and anti-CTLA-4 therapy remains unknown. Thus, we investigated a combination therapy of lycorine hydrochloride and anti-CTLA-4 using a murine RCC model. As a means of in vitro confirmation, we found that lycorine hydrochloride inhibited the viability of various RCC cell lines. Furthermore, luciferase-expressing Renca cells were implanted in the left kidney and the lung of BALB/c mice to develop a RCC metastatic mouse model. Lycorine hydrochloride and anti-CTLA-4 synergistically decreased tumor weight, lung metastasis, and luciferin-staining in tumor images. Importantly, the observed anti-tumor effects of this combination were dependent on significantly suppressing regulatory T cells while upregulating effector T cells; a decrease in regulatory T cells by 31.43% but an increase in effector T cells by 31.59% were observed in the combination group compared with those in the control group). We suggest that a combination of lycorine hydrochloride and anti-CTLA-4 is a viable therapeutic option for RCC patients.