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In the current study, we investigated a combination of docetaxel and thalidomide (DT therapy) in castration-resistant prostate cancer (CRPC) patients. We identified marker genes that predict the effect of DT therapy. Using an androgen-insensitive PC3 cell line, we established a docetaxel-resistant PC-3 cell line (DR-PC3). In DR-PC3 cells, DT therapy stronger inhibited proliferation/viability than docetaxel alone. Based on gene ontology analysis, we found versican as a selective gene. This result with the findings of cDNA microarray and validated by quantitative RT-PCR. In addition, the effect of DT therapy on cell viability was the same as the effect of docetaxel plus versican siRNA. In other words, silencing of versican can substitute for thalidomide. In the clinical setting, versican expression in prostate biopsy samples (before DT therapy) correlated with PSA reduction after DT therapy (p

Bladder cancer is the second most common genitourinary malignancy and has variable metastatic potential; however, choroidal and cutaneous metastases are extremely rare. Generally, a patient with these uncommon metastases has a very poor prognosis. We present a bladder cancer patient with a visual disorder in the right eye and multiple nodules on head and lower abdomen that developed 17 months after a radical cystectomy. These symptoms were determined to be caused by choroidal and cutaneous metastasis of bladder cancer. Although two cycles of combination chemotherapy were performed, the patient died 5 months after diagnosis of multiple metastases.

What's known on the subject? and What does the study add? The process of bladder regeneration with a bladder acellular matrix graft (BAMG) is thought to be accelerated by administration of vascular endothelial growth factor into the host bladder. In the present study, we showed that simultaneous implantation of bilateral ureters into a BAMG after a partial cystectomy is reasonable and provides an increased opportunity to the bio-scaffold for communication with host tissues from which a blood supply and stem cells will be generated. OBJECTIVE • To evaluate if the implantation of bilateral ureters into a bladder acellular matrix graft (BAMG) at the time of its implantation would enhance bladder regeneration in a partial substitution BAMG. MATERIALS AND METHODS • Partial cystectomies were performed under general anaesthesia in 12 pigs, followed by augmentation with a BAMG. • Six (ureteric implantation group) also received simultaneous implantation of bilateral ureters into the BAMG, while the remaining six (control group) did not have ureteric implantation. • In both groups, bladder regeneration was evaluated using endoscopic and histopathological methods at 1, 2, 4, and 8 weeks after implantation. RESULTS • At 1 week after BAMG implantation, there were significant inflammatory changes on the host bladder in both groups, while no significant endoscopic changes were seen on the BAMG luminal surfaces. • At 2 weeks, inflammatory changes were diminished and epithelialisation on the BMAG was identified, especially near the host bladder in both groups. • Similarly, epithelialisation on the BAMG near the implanted ureters was seen in the ureteric implantation group. • At 4 and 8 weeks, epithelialisation remained in progress in both groups, although it was more active and expansive in the ureteric implantation group. CONCLUSIONS • In our porcine model, endoscopic and histopathological examinations showed that simultaneous implantation of bilateral ureters into a BAMG enhanced epithelialisation of the AMG. • This new approach using host ureters and bladder as a potential source of bladder regeneration may provide for rapid and complete regeneration of a bladder substitute.

To determine the definite border between normal and tumor kidney tissues during partial nephrectomy (PN) procedures using intraoperative indocyanine green (ICG)-based fluorescence imaging.Sixteen potential candidates for PN with organ-confined, small renal masses treated between July 2008 and June 2011 at Shimane University Hospital were enrolled. An ICG-based fluorescence navigation (FN) system was used to evaluate the border between the tumor and normal kidney parenchyma (step 1), the cavity following tumor excision (step 2), and the negative surgical margin of resected tissues (step 3). The R.E.N.A.L nephrometry score (RNS) was applied to evaluate the correlation between tumor anatomy and ICG-based fluorescence imaging.In step 1, in vivo probing revealed 14 tumors with a mean RNS of 7 points that showed quite low ICG fluorescence signals in the tumor mass as compared with normal kidney parenchyma. In step 2, in vivo probing around the bed revealed highly fluorescent signals with no remnant tumor residing in 10 cases with a mean RNS of 6 points. In step 3, ex vivo probing revealed cancer tissues involving normal parenchyma that were completely excised with minimum amounts of normal parenchyma in all 16 resected specimens.ICG-based FN system was very helpful for confirming negative margin status in even the most complex cases. Further evaluations may open the door for widespread use of this ICG-based FN system as a feasible and attractive alternative during a PN procedure.

Objective: The objective of this study was to identify lymphatic vessels draining from the prostate by using a fluorescence navigation (FN) system. Methods: Fourteen subjects were candidates for radical retropubic prostatectomy (RRP) and pelvic lymph node dissection (PLND). After an indocyanine green solution was injected into the prostate during RRP, lymphatic vessels draining from the prostate were analyzed using a FN system. After PLND based on lymphatic mapping by the FN system (in vivo probing) was performed in the external iliac, obturator and internal iliac regions; the fluorescence of the removed lymph nodes (LNs) was analyzed on the bench (ex vivo probing). Results: Under in vivo and ex vivo probing, the fluorescence intensity of internal iliac nodes was greater than that of external iliac or obturator nodes. Conclusion: The current study suggests that using a FN system after injecting indocyanine green is a safe and rational approach for detecting the lymphatic channel draining from the prostate. The major lymphatic pathway involved in the spreading of prostate cancer appears to relate to internal iliac LNs, which would mean that the standard PLND covering external iliac and obturator regions would not keep the cancer from spreading. Objectif : L’objectif de l’etude etait de reperer les vaisseaux lymphatiques quittant la prostate a l’aide d’un systeme d’imagerie par fluorescence (IF). Methodologie : Quatorze sujets devaient subir une prostatectomie radicale retropubienne (PRR) et une lymphadenectomie pelvienne. Apres injection d’une solution de vert d’indocyanine dans la prostate pendant la PRR, les vaisseaux lymphatiques drainant la prostate ont ete analyses par IF. Une lymphadenectomie pelvienne fondee sur la cartographie lymphatique par IF (exploration in vivo) a ensuite ete realisee dans les regions de la fosse iliaque externe, de l’obturateur et de la fosse iliaque interne; la fluorescence des ganglions lymphatiques retires a ete analysee sans delai (exploration ex vivo). Resultats : Lors de l’exploration in vivo et ex vivo, l’intensite de la fluorescence des ganglions iliaques internes etait plus forte que celle des ganglions iliaques externes ou des ganglions obturateurs. Conclusion : Cette etude porte a croire que l’IF apres injection de vert d’indocyanine est une methode sure et rationnelle pour reperer les vaisseaux lymphatiques drainant la prostate. La principale voie lymphatique de propagation du cancer de la prostate semble etre reliee aux ganglions lymphatiques iliaques internes, ce qui signifie que la lymphadenectomie pelvienne standard retirant les ganglions iliaques externes et obturateurs n’empecherait pas le cancer de se propager.

OBJECTIVE To investigate the longitudinal alteration of health-related quality of life (HRQL) up to 5 years after radical perineal prostatectomy (RPP) among Japanese patients with localized prostate cancer. PATIENTS AND METHODS In all, 194 patients who had RPP were included in this longitudinal survey. The validated RAND 36-Item Health Survey (SF-36) and the University of California, Los Angeles Prostate Cancer Index (UCLA-PCI) were used to evaluate the HRQL. RESULTS Among the UCLA-PCI urinary domains, urinary function scores decreased at 3 months after RPP, but they increased 6 months after RPP. Likewise, urinary bother showed a transient decrease at 3 months, but had returned to the baseline level 6 months after RPP. Sexual function (SF) was drastically decreased at 3 months after RPP, but had slightly increased 1 year after RPP. Patients who had a nerve-sparing (NS) RPP showed better SF-related HRQL than those who did not at 6 months after RPP. This favourable alteration involving SF-related HRQL was closely associated with the NS procedure, but not with the patient age. Multivariate analysis showed that later recovery of SF was essentially related to the use of NS RPP, while early recovery of sexual bother was closely related to the patient age. CONCLUSIONS Our results confirmed the positive effect of RPP on the long-term HRQL in Japanese patients. Although NS surgery conferred the benefit of the recovery of SF, older Japanese patients were not greatly concerned about their decreased SF-related HRQL. The current results provide primary evidence for predicting the alteration of HRQL and understanding the effect of patient age and NS surgery on HRQL after RPP.

INTRODUCTION AND OBJECTIVES: Efficacy in the prostate cancer detection of real-time tissue elastogarpahy (RTE) has been reported. But RTE has a major problem that RTE is highly operator dependent procedure. We hypothesized that the pressure device might decrease the operator dependency and increase the prostate cancer detection rate of RTE. The pressure device run with water pressure was developed for this study, called this procedure real-time balloon inflation elastography (RBIE). The results of targeted prostate biopsy with RBIE was studied for detection of prostate cancer. METHODS: 233 patients and 1978 were enrolled in this study with abnormal findings of digital rectal examination (DRE), PSA and/ or TRUS. Median age was 73 year-old (range 54e89), median PSA was 7.6 ng/mL (range 0.8-2606.0), and median number of biopsy cores taken on each patient was 8 (range 8e10). All of 233 patients were examined with MRI prior to prostate needle biopsy. A total of 1978 specimens obtained by systemic biopsy were studied. The findings of RBIE, RTE, TRUS, PDUS and MRI (T2WI, dynamic contrast enhanced images (DCEI) and diffusion weighted image (DWI)) were compared to the histopathological findings of biopsy specimens. RESULTS: The prostate cancer was detected in 113 of 233 patients (48.5%), and 412 of 1978 specimens (20.8%). Gleason score of 5 to 6, 7 and 8 to 10 tumors was 110, 166 and 138 specimens respectively. Clinical stages of T1c, T2a-c, T3a-b, and T4 were 20, 60, 22 and 11 cases. The sensitivity of RBIE, RTE, TRUS, PDUS, T2WI, DCEI and DWI were 72.1%, 72.1%, 74.5%, 72.8%, 78.2%, 77.2% and 77.2%, the specificity were 94.3%, 93.6%, 85.4% 90.5%, 92.0%, 93.7% and 92.6%, respectively. Both of the sensitivity and the specificity of RBIE were not significantly inferior to those of MRI. The results of targeted biopsy (PPV) of RBIE, RTE, TRUS, PDUS, T2WI, DCEI and DWI were 76.7%, 74.8%, 57.4%, 67.0%, 72.0%, 76.4% and 73.3%. PPV of RBIE was also comparable to those of MRI. CONCLUSIONS: RBIE was low cost and low invasive procedure. The prostate cancer detection capability of RBIE might be not inferior to that of MRI, expensive and time consuming procedure. Furthermore, RBIE reveals prostate in real-time, so RBIE could enhance the prostate cancer detection as a biopsy guidance image.

In kidney transplant recipients, acute renal failure resulting from a ureteral obstruction by fungus balls is uncommon. We report a 60-year-old man diagnosed with ureteral obstruction caused by Candida albicans fungus balls early after transplant. Diagnosis was made by a T2-weighted magnetic resonance image, which demonstrated fungus balls as a low-intensity mass in the pelvis and microscopic examination findings in the urine. The patient was treated successfully with an antifungal agent and direct irrigation. It should be noted that fungus balls may cause ureteral obstruction of transplanted kidneys, possibly resulting in graft failure. Imaging of the kidneys and collecting system and aggressive debridement that adds to systemic therapy are necessary for early diagnosis and are central to a successful outcome.

protein (BMP)-2, a member of the transforming growth factor b superfamily, has been shown to act as a tumor suppressor in several cancers by activating signaling cascades that cause cell cycle arrest. In addition, the expression level of BMP-2 is downregulated because of promoter CpG hypermethylation. We hypothesized that impaired regulation of BMP-2 through epigenetic pathways is associated with the pathogenesis of renal cell carcinoma. METHODS: To test this hypothesis, CpG methylation of the BMP-2 gene was analyzed in 3 renal tumor cell lines and 96 renal tumor and matched normal renal tissue. Promoter CpG methylation was analyzed by methylation specific PCR using bisulfite-modified DNA as template. BMP-2 expression was measured by quantitative RT-PCR. RESULTS: BMP-2 mRNA expression was significantly enhanced after 5-aza-2€ treatment in renal tumor cell lines. The prevalence of BMP-2 promoter methylation was significantly higher and BMP-2 mRNA expression was significantly lower in renal tumor samples than in normal kidney samples (p

Introduction and Objective. Indocyanine green (ICG) emits infrared light with exposure to laser light. When intravenously injected, it binds to plasma proteins and predominantly persists in the vasculature, which is very useful for definition of the vascular network. The HyperEye Medical System (HEMS; Mizuho Ikakogyo Co., LTD, Tokyo, Japan) is a new device able to identify both near-infrared and visible rays “in situ” without needing to dim the operation room lighting. We speculated that intraoperative ICG imaging would be applicable for kidney transplantation, by providing “in situ” determination of successful vascular anastomosis. Materials and Methods. Four patients underwent intraoperative ICG imaging following intravenous administration of 1 mL of a solution containing 0.25% ICG. After performing vascular anastomosis, the allograft was examined using the HEMS light source device. Fluorescent signals were transmitted to a digital video processor connected to a television monitor and evaluated in real time. Results. In all 4 patients, intraoperative ICG imaging provided excellent resolution of blood flow at each step in real time, namely, coming from the recipient’s artery to the allograft renal artery, circulating throughout the whole grafted kidney, and draining through the allograft renal vein to the recipient’s vein. HEMS provides ICG fluorescence image in color, allowing surgeons to clearly discriminate the positional relationship between the target tissue and the surrounding tissue. No complications associated with ICG injection were noted. Conclusion. Our preliminary results indicate that HEMS is a feasible and safe ICG imaging system that helps prevent technical failure during vascular anastomosis, and also demonstrates blood supply to the grafted kidney.

Background: The expression level of protein G product 9.5 (PGP9.5) is downregulated because of promoter CpG hypermethylation in several tumors. We speculated that impaired regulation of PGP9.5 through epigenetic pathways is associated with the pathogenesis of prostate cancer. Methods: CpG methylation of the PGP9.5 gene was analyzed in cultured prostate cancer cell lines, 226 localized prostate cancer samples from radical prostatectomy cases, and 80 benign prostate hyperplasia (BPH) tissues. Results: Following 5-aza-2′-deoxycytidune treatment, increased PGP9.5 mRNA transcript expression was found in the LNCaP and PC3 cell lines. With bisulfite DNA sequencing, partial methylation of the PGP9.5 promoter was shown in LNCaP whereas complete methylation was found in PC3 cells. After transfection of PGP9.5 siRNA, cell viability was significantly accelerated in LNCaP but not in PC3 cells as compared with control siRNA transfection. Promoter methylation of PGP9.5 was extremely low in only one of 80 BPH tissues, whereas it was found in 37 of 226 prostate cancer tissues. Expression of the mRNA transcript of PGP9.5 was significantly lower in methylation (+) than methylation (−) prostate cancer tissues. Multivariate analysis of biochemical recurrence (BCR) after an radical prostatectomy revealed pT category and PGP9.5 methylation as prognostically relevant. Further stratification with the pT category in addition to methylation status identified a stepwise reduction of BCR-free probability. Conclusion: This is the first clinical and comprehensive study of inactivation of the PGP9.5 gene via epigenetic pathways in primary prostate cancer. Impact: CpG methylation of PGP9.5 in primary prostate cancer might become useful as a molecular marker for early clinical prediction of BCR after radical prostatectomy. Cancer Epidemiol Biomarkers Prev; 21(3); 487–96. ©2012 AACR.

A 65-year-old man (blood type O) came to our hospital for transplant of an unrelated kidney (6/6 mismatch of HLA genotype) donated by his living 60-year-old wife (blood type B). The planned right donor nephrectomy was uneventful, with a warm ischemic time of 5 minutes, but her right renal vein was too fragile and weak to be repaired for vascular anastomosis. Therefore, we used an artificial vascular graft (polytetrafluoroethylene) interposed between the donor renal vein and the recipient's left external iliac vein. On the 11th day after surgery, infraphrenic free air (identified by a chest radiograph) made us do an emergent laparoscopic examination that showed a perforation of his sigmoid colon. A transient transverse colostomy was therefore prepared. The transient transverse colostomy was closed 8 months after the kidney transplant. Twelve months after the transplant, the patient is doing well with a serum creatinine level of 150.44 micromol/L (1.7 mg/dL).

statistically equivalent improvements in IPSS and PVR postoperatively. CONCLUSIONS: Men with an elevated BMI had significantly less improvement in Qmax following laser prostatectomy than men with normal BMI. However, BMI had no influence on improvement in IPSS or PVR. This data may assist urologists when counseling overweight men regarding their expectations of symptom relief following laser prostatectomy.

OBJECTIVE To analyse the distance between the ipsilateral neurovascular bundles (NVBs) and foci of prostate cancer (N-T distance) in specimens removed by radical prostatectomy (RP) and identify the predictor for N-T distance for preserving the ipsilateral NVB, as an accurate understanding of the anatomical relationship between prostate cancer foci and the NVB is necessary for establishing the indications for the appropriate use of nerve-sparing (NS) modifications of RP. PATIENTS AND METHODS The study included 245 patients with prostate cancer who had RP through the perineal or retropubic approach between June 2000 and November 2006. The analysis focused on 302 foci of prostate cancer (192 cases), which involved at least the posterolateral region of the prostate. The N-T distance was separately measured in the apex, middle and base of the prostate, and was correlated with the maximum diameter and Gleason score of the foci, and the preoperative prostate-specific antigen (PSA) level. RESULTS The mean N-T distance was 2.98, 2.95 and 3.03 mm in the apex (216 foci), middle (195 foci) and base (80 foci), respectively. In the apex, the N-T distance was related to both tumour size and preoperative PSA value (P

Metastatic prostate cancer (PC) is incurable by androgen deprivation therapy alone, due to the presence of androgen-independent/supersensitive cells in hormone-naive PC. A 67-year-old man was diagnosed with PC (Gleason score, 5 + 4) with multiple bone metastases. He was treated by chemohormonal therapy with cisplatin and estramustine phosphate (EMP) followed by maximal androgen blockade, and showed a complete response. As of the time of writing, no clinical or prostate-specific antigen recurrence has been observed for over 15 years, despite cessation of the treatment. This is the first report to indicate a possible cure of metastatic PC by chemohormonal therapy combined with appropriate anti-tumor drugs targeted to both androgen-independent and -dependent clones before the hormone-refractory state.

Objectives To determine the safety and efficacy of combination chemotherapy with docetaxel (DTX), estramustine phosphate (EMP), and carboplatin (CBDCA) in patients with hormone-refractory prostate cancer (HRPC). Methods This study included a total of 40 HRPC patients. We evaluated the activity of the following schedule: weekly DTX 30mg/m 2 iv, daily EMP 10mg/kg po, and CBDCA AUC=6 iv on day 1 of a every 4-wk cycle. Treatment was continued until disease progression or excessive toxicity. Results All patients were assessable for response. A median of six consecutive cycles was administered per patient. Levels of prostate-specific antigen decreased by more than 50% in 95.0% of the patients. Consumption of medication for cancer-induced pain was reduced in 84.6%. Partial response was attained in 66.7% of measurable lesions. Of patients with bone metastasis, 8.3% demonstrated partial response. With a median follow-up of 11.4 mo, the median time to progression was 12.0 mo, and the median overall survival time was 26.6 mo. The predominant toxicities were grade-3 or -4 anemia in 32.5% of the patients, leukopenia in 20.0%, and thrombocytopenia in 17.5%. However, all toxicity was temporary and reversible with dose reduction or temporary cessation of chemotherapeutic agents. There were no therapy-related deaths. Conclusions Combination chemotherapy with DTX/EMP/CBDCA was found to have significant clinical activity with an acceptable toxicity profile in HRPC patients. More suitable selection of patients may be beneficial in terms of improved overall survival in the future.

1964 VALIDATION OF SUBJECTIVE BENEFIT AFTER INTRAPROSTATIC BOTULINUS TOXIN A INJECTION IN PATIENTS WITH PROSTATIC HYPERTROPHY – AN EVIDENCE BY REAL-TIME TISSUE ELASTOGRAPHY Takeo Hiraoka*, Hiroaki Shiina, Shogo Inoue, Masahiro Sumura, Shinji Urakami, Satoshi Honda, Koji Wake, Mikio Igawa. Izumo, Japan. INTRODUCTION AND OBJECTIVE: Recent reports have indicated intraprostatic botulinus toxin A (BTX-A) injection as an attractive alternative to TUR-P. The purpose of this study is to validate the clinical usefulness of BTX-A injection into the prostate as a minimal invasive treatment for BPH. METHODS: Twenty-two BPH patients (average age 74 years old) were employed in this study. The eligible criteria for inclusion are

Objectives: To validate the feasibility and implications of a hybrid procedure using perineal and abdominal approaches for a radical prostatocystectomy. Methods: Between March 2007 and May 2012, we performed 16 prostatocystectomy and simultaneous urethrectomy under a hybrid procedure using perineal and abdominal approach for advanced bladder cancer. The hybrid procedure was selected in each case, because of prostatic urethra involvement in 13 and prior treatment in 3 (irradiation, radical retropubic prostatectomy, and sigmoidectomy, respectively). Two surgical teams, one responsible for the perineal approach and the other for the abdominal portion, performed the operation. Results: The median operation time for the prostatocystectomy procedure was 207 minutes and median intraoperative blood loss was 1665 ml. The en bloc removal of the specimen was perfectly performed and no intraoperative difficulties and intraoperative complications such as rectal injury were recognized in all cases. As for postoperative complications associated with the exaggerated lithotomy position, neurologic complications and rhabdomyolysis which could be treated conservately were found in 1 case. Although 5 patients died from distant metastasis, local recurrence was not seen in any of the 16 patients during the follow-up period. Conclusion: The hybrid procedure using perineal and abdominal approach for radical prostatocystectomy is a well-organized procedure that can provide good visualization of the surgical structure around the prostate, leading to a reduction in or prevention of local recurrence and surgical complications even in the selected patient.