Versican is a potential therapeutic target in docetaxel-resistant prostate cancer.

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<0.05). Thus targeting versican is a potential therapeutic strategy in docetaxel-resistant prostate cancer.

Case report of a ureteral obstruction by Candida albicans fungus balls detected by magnetic resonance imaging in kidney transplant recipient.

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.

Hybrid procedure using perineal and abdominal approaches for radical prostatocystectomy: initial experience with 16 select cases.

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.

Prostate 3T-MR spectroscopic imaging without an endorectal surface coil using the MLEV-PRESS sequence.

PURPOSE: The aim of this study was to determine to what extent we could identify the metabolism product peak using 3-T proton magnetic resonance spectroscopic imaging (MRSI) of the prostate gland in healthy volunteers by combining an external array coil with Malcolm Levitt composite-pulse decoupling sequence (MLEV)-point-resolved spatially localized spectroscopy (PRESS). MATERIALS AND METHODS: MRSI data were obtained from the entire prostate gland in six healthy volunteers. The heights of the choline, citrate peaks and the standard deviation (SD) of the noise in each voxel were calculated. When the choline and/or citrate peak in a voxel exceeded 3 SD, the peak was clearly identified. RESULTS: The clear citrate peak rate in the peripheral zone (PZ) and the central gland (CG) were 78.8 and 70.3 %, respectively. The clear choline peak rate in the PZ and the CG were 55.4 and 44.9 %, respectively. In addition, the clear peak rates for both citrate and choline in the PZ and the CG were 51.8 and 38.6 %. Therefore, in the entire prostate gland, 75.2 % had a clear citrate peak, 51.1 % had a clear choline peak, and 46.3 % had both citrate and choline peaks. CONCLUSION: The citrate peak was clearly detected in 75.2 % of the voxels by this technique.

Tumor suppressor function of PGP9.5 is associated with epigenetic regulation in prostate cancer--novel predictor of biochemical recurrence after radical surgery.

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.

Indocyanine green (ICG)-based fluorescence navigation system for discrimination of kidney cancer from normal parenchyma: application during partial nephrectomy.

PURPOSE: To determine the definite border between normal and tumor kidney tissues during partial nephrectomy (PN) procedures using intraoperative indocyanine green (ICG)-based fluorescence imaging. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Identification of lymphatic pathway involved in the spreading of prostate cancer by fluorescence navigation approach with intraoperatively injected indocyanine green.

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.

Rare complication of a sigmoid colon perforation after a kidney transplant with an artificial vascular graft.

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).

Impact of a novel, extended approach of perineal radical prostatectomy on surgical margins in localized prostate cancer.

STUDY TYPE: Therapy (case series) Level of Evidence 4. OBJECTIVE: To validate the rationale of extended perineal radical prostatectomy (ePRP) for treating localized prostate cancer. PATIENTS AND METHODS: Between December 2000 and May 2007, 196 patients with localized prostate cancer underwent PRP, among which 91 and 105 patients were treated with conventional PRP (cPRP) and ePRP, respectively. The apex, middle, base, and anterior regions of the prostate were separately analysed, and the focus of analysis was on the distribution, size, Gleason score, and positive surgical margins (PSMs) of prostate cancer foci. RESULTS: The operation time was significantly shorter in ePRP compared with cPRP (161 min vs 188 min; P= 0.001), while there was no significant difference in estimated blood loss between cPRP and ePRP (550 mL vs 500 mL). At the apex and base, there was no significant difference in the PSM rate between cPRP and ePRP. In the middle, there was a lower incidence of PSMs in ePRP (2.4%) than in cPRP (10.9%; P= 0.009). On the anterior side, PSMs were more frequent in cPRP (21.6%) than in ePRP (7.1%; P= 0.029). Logistic regression analysis adjusted by PSA level showed that PSM rate was the most significantly affected by the surgical approach. CONCLUSION: We think that ePRP provides an effective treatment strategy for localized prostate cancer in light of excellent cancer control and minimum potential of surgical invasiveness.

Five-year longitudinal effect of radical perineal prostatectomy on health-related quality of life in Japanese men, using general and disease-specific measures.

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.

Retrospective analysis of the distance between the neurovascular bundle and prostate cancer foci in radical prostatectomy specimens: its clinical implication in nerve-sparing surgery.

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 < 0.001 and P < 0.05, respectively). In the base, tumour size was related to the N-T distance (P < 0.01), but the preoperative PSA level was not related to the N-T distance. In the middle, the association of tumour size with N-T distance was of borderline significance (P = 0.07). Irrespective of tumour location, the Gleason score did not contribute to the N-T distance. CONCLUSIONS: These findings show the basic information necessary when making a decision to perform NS-RP in patients with localized prostate cancer. The application of N-T distance could provide a better strategy for determining indications that warrant the use of NS RP than with the conventional tactile feedback approach.

Long-term control or possible cure? Treatment of stage D2 prostate cancer under chemotherapy using cisplatin and estramustine phosphate followed by maximal androgen blockade.

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.

[Recent progress in diagnostic radiology for urinary system malignant tumors].

The clinical effectiveness and utility of diagnostic radiology with various new technologies and examination methods under development are under investigation. In diagnostic radiology of urinary system malignant tumors, trans-abdominal echography is accepted for screening in terms of ease and safety. But there is a problem in spatial resolution, and contrasting echography and doppler echography are awaited. In diagnostic radiology of a kidney and upper urinary tract system, MDCT (Multidetector-row CT) is the most used,because MDCT provides high time advantages, spatial resolution and widespread availability. However, the method of choice with MRI is under review given the problem of contrast media. MDCT effectiveness is reported in diagnostic radiology of the bladder, but MRI is used for invasion depth diagnosis by means of high tissue contrast. In diagnostic radiology of prostate cancer, the utility of DWI (diffusion-weighted image) and MRS (MR spectroscopy) is reported. As for 18 F-FDG-PET (positron emission tomography)/CT, evaluation of primary lesions is insufficient, since incides are excreted by the urinary tract,but it is effective for a metastatic diagnosis. It is thought that an image diagnostic procedure changes more in future by the direction for uses of contrast media, the newly technical use, a contrasting echography and new isotope PET/CT.

Initial evaluation of prostate cancer with real-time elastography based on step-section pathologic analysis after radical prostatectomy: a preliminary study.

OBJECTIVE: To determine whether real-time elastography can be used to detect prostate cancer as a relatively non-invasive modality based on the tissue strain value. PATIENTS AND METHODS: Seventeen patients underwent real-time elastography in conjunction with digital rectal examination (DRE), conventional gray-scale transrectal ultrasonography (TRUS), color Doppler ultrasonography (CDUS), and magnetic resonance imaging (MRI) prior to radical prostatectomy. The elastogram was compared to findings of conventional modalities and pathological findings of prostatectomy specimens. To obtain the elastogram, compression of the prostate was performed along with a visual indicator on a video screen. RESULTS: Twenty of 27 pathologically confirmed tumors were detected with real-time elastography. The cancer detection rate with real-time elastography was superior to the rates of other modalities and nearly equal to both on the anterior side (75.0%) and the posterior side (73.7%) of the prostate. A higher tumor detection rate for real-time elastography was observed for tumors with a higher Gleason score and larger tumor volume. CONCLUSION: In our preliminary study, real-time elastography in conjunction with gray-scale TRUS is a non-invasive modality to detect prostate cancer.

Phase-II study of docetaxel, estramustine phosphate, and carboplatin in patients with hormone-refractory prostate cancer.

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 30 mg/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.