Low-dose docetaxel, estramustine and prednisolone combination chemotherapy for castration-resistant prostate cancer.

The objective of this study was to report our experience with weekly low-dose docetaxel (DOC) chemotherapy for patients with castration-resistant prostate cancer (CRPC). From 2007 to 2014, 39 consecutive patients received weekly low-dose DOC; the oncological effectiveness, side effects and tolerability were prospectively analyzed. The median patient age, serum prostate-specific antigen (PSA) level and Gleason score at diagnosis of prostate cancer were 71 years (range, 55-83 years), 187 ng/ml (range, 2.0-1711 ng/ml) and 8 (range, 5-10), respectively. The median number of cycles of DOC was 7 (range, 1-45 cycles). Of the 39 patients, the PSA level decreased by >50% in 13 (33%). In the multivariate analysis of prediction of patient overall survival, a decrease of the PSA level to <50% was a significant predictor (hazard ratio = 6.913; 95% confidence interval: 1.147-41.669; P=0.035). The median cancer-specific overall survival from the diagnosis of CRPC was 16.7 months (range, 2-54 months). Grade 3 toxicities were observed in 5 patients (13%); specifically, limb edema, nausea and hepatic disorders were detected in 2 (5%), 2 (5%) and 1 patient (3%), respectively. Treatment-related death (grade 5) occurred in 1 patient due to interstitial pneumonia after two courses of chemotherapy. The chemotherapy was completed in the majority of the patients (n=37, 94.8%) in the outpatient department, without interruption. These findings suggest that weekly low-dose DOC is feasible and safe for selected patients with CRPC, without treament with novel agents, such as abiraterone, enzalutamide and cabazitaxel.

Urethra-sparing high-intensity focused ultrasound for localized prostate cancer: Functional and oncological outcomes.

OBJECTIVES: To evaluate longitudinal changes in urinary function and quality of life, and the oncological outcomes of patients treated with urethra-sparing high-intensity focused ultrasound for localized prostate cancer. METHODS: Patients with negative findings in the urethra and the anterior urethral zone using transrectal ultrasound-guided targeted biopsies, and magnetic resonance imaging, received urethra-sparing or whole-gland high-intensity focused ultrasound as the primary therapy for localized prostate cancer without transurethral resection of the prostate. Longitudinal changes in urinary function and quality of life, and the oncological outcomes of the patients were analyzed retrospectively. RESULTS: The median follow-up times for urethra-sparing and whole-gland high-intensity focused ultrasound were 36 and 30 months, respectively. Comparing the patients treated with urethra-sparing high-intensity focused ultrasound (n = 45) with those treated with whole-gland high-intensity focused ultrasound (n = 65), there were significant differences in the International Prostate Symptom Score (P = 0.014) at 3 months, International Prostate Symptom Score quality of life (P = 0.033) at 3 months, maximum urinary flow rate (mL/s; at 3 months, P = 0.010; at 6 months, P = 0.038) and residual urine volume (mL; at 3 months, P < 0.0001; at 6 months, P = 0.016; at 12 months, P = 0.028). For quality of life, there were significant differences in Functional Assessment of Cancer Therapy - General (at 3 months, P = 0.022) and Functional Assessment of Cancer Therapy - Prostate (at 3 months, P = 0.028; at 6 months, P = 0.034). There were no significant differences in oncological outcomes regarding negative biopsy rates on follow up (91% vs 92%; P = 0.8) or biochemical disease-free survival rates (86.7% vs 89.2%; P = 0.7). CONCLUSIONS: Urethra-sparing high-intensity focused ultrasound might prevent prolonged bladder outlet obstruction, and could be a treatment option for localized prostate cancer.

Morphological analysis of the effects of intraoperative transrectal compression of the prostate during high-intensity focused ultrasound for localized prostate cancer.

OBJECTIVES: To evaluate the effects of transrectal compression of the prostate for intra-operative prostatic swelling and intraprostatic point shift during high-intensity focused ultrasound treatment of localized prostate cancer. METHODS: Patients treated with whole-gland high-intensity focused ultrasound as primary monotherapy for localized prostate cancer were enrolled in the study. Using the standard and compression method, the volumes of degassed water in the balloon covering the high-intensity focused ultrasound probe were 50 mL and 80-160 mL, respectively. To identify prostatic swelling and shift during high-intensity focused ultrasound and the volume occupied by the non-enhanced area, three-dimensional prostate models were reconstructed using ultrasound and contrast-enhanced magnetic resonance imaging. RESULTS: In comparison with the standard (n = 40) and compression (n = 48) methods, intraoperative increase in the prostate volume (21% vs 5.3%; P = 0.044), intraprostatic point shift (4 mm vs 2 mm, P = 0.040 in the transition zone; 3 mm vs 0 mm; P = 0.001 in the peripheral zone) and the volume occupied by the non-enhanced area (89% vs 96%; P = 0.001) were significantly suppressed. The biochemical disease-free survival rate in patients treated using the compression method was significantly improved relative to the standard method (92.6% vs 76.5%; P = 0.038). Regarding complications, there was no significant difference in the rate of urethral stricture (P = 0.9), urinary tract infection (P = 0.9), incontinence (P = 0.3), erectile dysfunction (P = 0.9) or recto-urethral fistula between the patients treated using the standard and compression methods. CONCLUSIONS: Intraoperative transrectal compression suppresses intraoperative increase in the prostate volume and intraprostatic point shift during high-intensity focused ultrasound, having the potential to achieve precise whole-gland and lesion-targeted focal therapy.

Improved outcomes with advancements in high intensity focused ultrasound devices for the treatment of localized prostate cancer.

PURPOSE: We evaluated the association between long-term clinical outcomes and morbidity with high intensity focused ultrasound. MATERIALS AND METHODS: We included patients with stage T1c-T3N0M0 prostate cancer who were treated with Sonablate® (SB) devices during 1999 to 2012 and followed for more than 2 years. Risk stratification and complication rates were compared among the treatment groups (ie SB200/500 group, SB500 version 4 group and SB500 tissue change monitor group). Primary study outcomes included overall, cancer specific and biochemical disease-free survival rates determined using Kaplan-Meier analysis (Phoenix definition). Secondary outcomes included predictors of biochemical disease-free survival using Cox models. RESULTS: A total of 918 patients were included in the study. Median followup in the SB200/500, SB500 version 4 and the SB500 tissue change monitor groups was 108, 83 and 47 months, respectively. The 10-year overall and cancer specific survival rates were 89.6% and 97.4%, respectively. The 5-year biochemical disease-free survival rate in the SB200/500, SB500 version 4 and SB500 tissue change monitor group was 48.3%, 62.3% and 82.0%, respectively (p < 0.0001). The overall negative biopsy rate was 87.3%. On multivariate analysis pretreatment prostate specific antigen, Gleason score, stage, neoadjuvant androgen deprivation therapy and high intensity focused ultrasound devices were significant predictors of biochemical disease-free survival. Urethral stricture, epididymitis, urinary incontinence and rectourethral fistula were observed in 19.7%, 6.2%, 2.3% and 0.1% of cases, respectively. CONCLUSIONS: Long-term followup of patients with high intensity focused ultrasound demonstrated improved clinical outcomes due to technical, imaging and technological advancements.

Manually controlled targeted prostate biopsy with real-time fusion imaging of multiparametric magnetic resonance imaging and transrectal ultrasound: an early experience.

OBJECTIVES: To report our early experience with manually controlled targeted biopsy with real-time multiparametric magnetic resonance imaging and transrectal ultrasound fusion images for the diagnosis of prostate cancer. METHODS: A total of 20 consecutive patients suspicious of prostate cancer at the multiparametric magnetic resonance imaging scan were recruited prospectively. Targeted biopsies were carried out for each cancer-suspicious lesion, and 12 systematic biopsies using the BioJet system. Pathological findings of targeted and systematic biopsies were analyzed. RESULTS: The median age of the patients was 70 years (range 52-83 years). The median preoperative prostate-specific antigen value was 7.4 ng/mL (range 3.54-19.9 ng/mL). Median preoperative prostate volume was 38 mL (range 24-68 mL). The number of cancer-detected cases was 14 (70%). The median Gleason score was 6.5 (range 6-8). Cancer-detected rates of the systematic and targeted biopsy cores were 6.7 and 31.8%, respectively (P < 0.0001). In six patients who underwent radical prostatectomy, the geographic locations and pathological grades of clinically significant cancers and index lesions corresponded to the pathological results of the targeted biopsies. CONCLUSION: Prostate cancers detected by targeted biopsies with manually controlled targeted biopsy using real-time multiparametric magnetic resonance imaging and transrectal ultrasound fusion imaging have significantly higher grades and longer length compared with those detected by systematic biopsies. Further studies and comparison with the pathological findings of whole-gland specimens have the potential to determine the role of this biopsy methodology in patients selected for focal therapy and those under active surveillance.

Prostate cancer with cyst formation detected by whole body positron emission tomography/computed tomography: A case report.

The present study reports a case of prostate adenocarcinoma with cyst formation. A 72-year-old male diagnosed with multiple lung metastases at a local clinic was referred to Tokai University Hachioji Hospital (Tokyo, Japan) for detection of a primary lesion. Whole body positron emission tomography/computed tomography showed strong accumulation of [18F]-fluoro-deoxy-2-glucose (FDG) in the small pelvis, and pelvic magnetic resonance imaging revealed a 60×40-mm cystic lesion, with an irregular thickened wall, behind the prostate. The serum prostate-specific antigen (PSA) level was elevated to 211.99 ng/ml, therefore, the patient underwent a transperineal prostate needle biopsy, and was diagnosed with prostate adenocarcinoma with cyst formation. Androgen deprivation therapy was administered for 8 months following the diagnosis of prostate cancer; consequently, the cyst reduced in size and the serum PSA level decreased to 0.14 ng/ml. To the best of our knowledge, this is the first report of a malignant prostatic cyst detected by FDG-positron emission tomography/computed tomography.

Time-dependent change of blood flow in the prostate treated with high-intensity focused ultrasound.

Avascular areas on contrast-enhanced magnetic resonance imaging have been considered to be areas of localized prostate cancer successfully treated by high-intensity focused ultrasound. However, the optimal timing of magnetic resonance imaging has not been discussed. The thermal effect of high-intensity focused ultrasound is degraded by regional prostatic blood flow. Conversely, the mechanical effect of high-intensity focused ultrasound (cavitation) is not affected by blood flow, and can induce vessel damage. In this series, the longitudinal change of blood flow on contrast-enhanced magnetic resonance imaging was observed from postoperative day 1 to postoperative day 14 in 10 patients treated with high-intensity focused ultrasound. The median rates of increase in the non-enhanced volume of the whole gland, transition zone and peripheral zone from postoperative day 1 to postoperative day 14 were 36%, 39%, and 34%, respectively. In another pathological analysis of the prostate tissue of 17 patients immediately after high-intensity focused ultrasound without neoadjuvant hormonal therapy, we observed diffuse coagulative degeneration and partial non-coagulative prostate tissue around arteries with vascular endothelial cell detachment. These observations on contrast-enhanced magnetic resonance imaging support a time-dependent change of the blood flow in the prostate treated with high-intensity focused ultrasound. Additionally, our pathological findings support the longitudinal changes of these magnetic resonance imaging findings. Further large-scale studies will investigate the most appropriate timing of contrast-enhanced magnetic resonance imaging for evaluation of the effectiveness of high-intensity focused ultrasound for localized prostate cancer.

Value of metastin receptor immunohistochemistry in predicting metastasis after radical nephrectomy for pT1 clear cell renal cell carcinoma.

KISS-1 is a metastasis-suppressor gene of human melanoma, and encodes metastin, which was identified as the ligand of a G-protein-coupled receptor (metastin receptor). The precursor protein is cleaved to 54 amino acids, which may be further truncated into carboxy-terminal fragments. Previous studies showed that lack of metastin receptor in clear cell renal cell carcinoma (RCC) is associated with tumor progression, but the prediction of metastasis in patients with pT1 clear cell RCC after radical nephrectomy is difficult. The objective of this study was to evaluate the usefulness of metastin receptor immunohistochemistry in predicting metastasis after nephrectomy for pT1 clear cell RCC. After verification of the correlation between immunostaining and mRNA expression, we evaluated the clinical value of metastin receptor immunohistochemistry. Fifty-four patients were enrolled in this study; following radical nephrectomy, seven patients were found to have lung metastasis. The sensitivity, specificity, positive predictive value, and negative predictive value with negative immunostaining of metastin receptor were 85.7, 97.6, 46.2, and 97.6 %, respectively. Metastasis-free survival rates were significantly higher in patients with positive staining (97.6 %) than in patients with negative staining (53.8 %) (P < 0.001). In univariate analysis for metastasis-free survival, negative immunostaining of metastin receptor was a significant risk factor for metastasis (P = 0.001). Furthermore, negative immunostaining of metastin receptor was an independent predictor for metastasis in multivariate analysis (hazard ratio, 3.735; 95 % CI 0.629-22.174; P = 0.002). In conclusion, our study suggests that negative expression of metastin receptor in clear cell RCC is significantly related to metastasis.

Dorsal vein complex preserving technique for intrafascial nerve-sparing laparoscopic radical prostatectomy.

OBJECTIVES: To describe a novel dorsal vein complex preserving technique for intrafascial nerve-sparing laparoscopic radical prostatectomy and to evaluate its postoperative outcomes. METHODS: A total of 109 patients who underwent laparoscopic radical prostatectomy by a single surgeon were evaluated, including 44 patients with dorsal vein complex preserving technique for intrafascial nerve-sparing laparoscopic radical prostatectomy, 20 patients with conventional intrafascial nerve-sparing laparoscopic radical prostatectomy and 45 patients with non-nerve-sparing laparoscopic radical prostatectomy. Functional outcomes were evaluated using a self-administered questionnaire (Expanded Prostate Cancer Index Composite). Continence was defined as zero to one security pad per day. Oncological outcomes were evaluated based on positive surgical margin. RESULTS: In the dorsal vein complex preserving technique for intrafascial nerve-sparing laparoscopic radical prostatectomy group, the continence rate was 57%, 77% and 95% at 1, 3 and 12 months, respectively. The continence rate in the conventional intrafascial nerve-sparing laparoscopic radical prostatectomy group was 37%, 63% and 90%, and in the non-nerve-sparing laparoscopic radical prostatectomy group it was 23%, 57% and 82% at 1, 3, and 12 months, respectively. The dorsal vein complex preserving technique for intrafascial nerve-sparing laparoscopic radical prostatectomy group showed a significantly earlier recovery from incontinence compared with that in the conventional intrafascial nerve-sparing laparoscopic radical prostatectomy and non-nerve-sparing laparoscopic radical prostatectomy groups (log-rank test, P = 0.044 and P < 0.001). Similarly, the dorsal vein complex preserving technique for intrafascial nerve-sparing laparoscopic radical prostatectomy group tended to show a more early recovery in relation to urinary function of the Expanded Prostate Cancer Index Composite. Regarding sexual function, there were no significant differences between the dorsal vein complex preserving technique for intrafascial nerve-sparing laparoscopic radical prostatectomy and conventional intrafascial nerve-sparing laparoscopic radical prostatectomy groups. In pT2 patients, the positive surgical margin rate of the dorsal vein complex preserving technique for intrafascial nerve-sparing laparoscopic radical prostatectomy group (11%) was similar to that of the other two groups (conventional intrafascial nerve-sparing laparoscopic radical prostatectomy 7%; non-nerve-sparing laparoscopic radical prostatectomy 11%). CONCLUSIONS: The dorsal vein complex preserving technique for intrafascial nerve-sparing laparoscopic radical prostatectomy technique provides early recovery from incontinence without adversely affecting the oncological outcome.

Distal pancreatectomy with en bloc celiac resection for locally advanced pancreas carcinoma.

In locally advanced pancreatic body cancers, cancer infiltrates major vessels such as the celiac axis, common hepatic artery and superior mesenteric artery or vein, which is the borderline of resectability. Patients also suffer severe abdominal pain. Kondo and Hirano et al. developed a radical operation called "distal pancreatectomy with en bloc celiac resection (DP-CAR)" for such cases. We applied this procedure three times in two patients with pancreatic body carcinomas, in which combined vascular resection was necessary. Radical operation was eventually achieved.