Noboru Numao

Development, Validation, and Head-to-Head Comparison of Logistic Regression-Based Nomograms and Artificial Neural Network Models Predicting Prostate Cancer on Initial Extended Biopsy

OBJECTIVES Using cohorts examined by extended biopsy, we developed and validated multivariate models predicting prostate cancer on initial biopsy and examined whether these extended biopsy-based models outperform previously established models. METHODS Initial extended biopsy (median 22 cores) was performed in 1509 Japanese men including 1083 at Tokyo Medical and Dental University Hospital (TMDU) and 426 at Cancer Institute Hospital (CIH). Logistic regression-based nomograms 1 and artificial neural network (ANN) 1 incorporating age, digital rectal examination, and prostate-specific antigen (PSA) and free PSA, and nomogram 2 and ANN2 further incorporating transrectal ultrasound (TRUS) findings and prostate volume were constructed on the TMDU data. These and previously established models were externally validated on the CIH data set and predictive accuracy was compared directly. RESULTS Without TRUS-derived information, nomogram 1 outperformed the ANN1. With TRUS-derived information, nomogram 2 was more accurate than ANN2. External validation revealed applicability of the Western models to Japanese population, superiority of the nomograms over ANN models, and better predictive accuracy of our extended biopsy-based nomograms than the previous 6-10-core biopsy-based models. Using nomograms 1 and 2, 16% and 19% unnecessary biopsies would be saved at 95% sensitivity. CONCLUSIONS We developed new nomograms predicting prostate cancer on initial biopsy in men with PSA <20ng/ml. Predictive accuracy of these extended biopsy-based nomograms is better than those of previously established models based on 6-10-core biopsies. Our models might help clinicians to decide if a patient requires biopsy and to avoid unnecessary biopsies.

Initial experience of diffusion-weighted magnetic resonance imaging to assess therapeutic response to induction chemoradiotherapy against muscle-invasive bladder cancer.

OBJECTIVES To investigate the feasibility of diffusion-weighted magnetic resonance imaging (DWI) in predicting therapeutic response to low-dose chemoradiotherapy (LCRT) against muscle-invasive bladder cancer (MIBC). Accurate assessment of response to induction therapy is an essential part of bladder-sparing therapeutic protocols against MIBC. However, conventional imaging studies are not useful in evaluating therapeutic response because of their inability to distinguish residual cancer from changes secondary to the treatment. METHODS Twenty patients with clinical T2-4aN0M0 bladder urothelial carcinoma (T2/T3/T4a: n = 10/8/2) who underwent induction LCRT comprising external beam radiotherapy to the bladder (40 Gy) concomitant with 2 cycles of cisplatin administration (20 mg/d for 5 days) followed by partial (n = 13) or radical cystectomy (n = 7) were prospectively enrolled. The patients underwent magnetic resonance imaging examinations with T2-weighted imaging (T2W), dynamic contrast-enhanced T1-weighted imaging (DCE), and DWI after LCRT. A finding of each protocol was compared with a pathologic finding of cystectomy specimen. RESULTS Pathologic examination of cystectomy specimens revealed pathologic complete response in 13 (65%) of the 20 patients. The sensitivity/specificity/accuracy of T2W, DCE, and DWI in predicting pathologic response was 43/45/44%, 57/18/33%, and 57/92/80%, respectively. Despite comparable sensitivity, DWI was significantly superior in specificity and accuracy to T2W (P = .03 and .02, respectively) and DCE (P = .002 for both). CONCLUSIONS This is the first study to show the feasibility of DWI over T2W and DCE for assessing therapeutic response to induction chemoradiotherapy against MIBC. The high specificity of DWI indicates that DWI is useful to accurately predict pathologic complete response, allowing more optimal patient selection in bladder-sparing protocols.

High Diagnostic Ability of Multiparametric Magnetic Resonance Imaging to Detect Anterior Prostate Cancer Missed by Transrectal 12-Core Biopsy

PURPOSE We clarified the diagnostic ability of multiparametric magnetic resonance imaging to reveal anterior cancer missed by transrectal 12-core prostate biopsy based on the results of 3-dimensional 26-core prostate biopsy, which is a combination of transrectal 12-core and transperineal 14-core biopsies. MATERIALS AND METHODS The study population consisted of 324 patients who prospectively underwent prebiopsy multiparametric magnetic resonance imaging and then 3-dimensional 26-core prostate biopsy at a single institution. We defined transrectal 12-core negative cancer as cancer detected by transperineal 14-core but not transrectal 12-core prostate biopsy. We focused on cancer in the anterior region. Any findings suspicious for malignancy in the region anterior to the urethra on multiparametric magnetic resonance imaging were defined as an anterior lesion on imaging. Significant cancer was defined as a biopsy Gleason score of 4 + 3 or greater, a greater than 20% positive core and/or a maximum cancer length of 5 mm or greater. Associations between an anterior lesion on imaging and transrectal 12-core negative cancer were investigated. RESULTS The overall cancer detection rate on 3-dimensional 26-core prostate biopsy was 39% (128 of 324 cases), of which 28% (36 of 128) were transrectal 12-core negative cancers. An anterior lesion on prebiopsy multiparametric magnetic resonance imaging was identified in 20% of men overall (65 of 324). Of men with and without an anterior lesion on imaging 40% (26 of 65) and 3.8% (10 of 259), respectively, had transrectal 12-core negative cancer. Significant transrectal 12-core negative cancer was observed in 0.4% (1 of 259 men) without an anterior lesion on imaging. Prebiopsy multiparametric magnetic resonance imaging revealed an anterior lesion in 92% of cases (11 of 12) of significant transrectal 12-core negative cancer. CONCLUSIONS Prebiopsy multiparametric magnetic resonance imaging has the potential to efficiently select men who could advantageously undergo anterior samplings, in addition to transrectal 12-core prostate biopsy.

Usefulness of Pre-biopsy Multiparametric Magnetic Resonance Imaging and Clinical Variables to Reduce Initial Prostate Biopsy in Men with Suspected Clinically Localized Prostate Cancer

PURPOSE We evaluated the usefulness of pre-biopsy multiparametric magnetic resonance imaging and clinical variables to decrease initial prostate biopsies. MATERIALS AND METHODS We prospectively evaluated 351 consecutive men with prostate specific antigen between 2.5 and 20 ng/ml, and/or digital rectal examination suspicious for clinically localized disease. All men underwent pre-biopsy multiparametric magnetic resonance imaging and initial 14 to 29-core biopsy, including anterior sampling. Three definitions of significant cancer were defined based on Gleason score and cancer volume (percent positive core and/or maximum cancer length). The overall cohort was divided into men at low risk-prostate specific antigen less than 10 ng/ml and normal digital rectal examination, and high risk-prostate specific antigen 10 ng/ml or greater and/or abnormal digital rectal examination. We evaluated the frequency of significant cancer according to magnetic resonance imaging and risk categories. Clinical variables as significant cancer predictors were analyzed using logistic regression. The sensitivity, specificity, and positive and negative predictive values of magnetic resonance imaging were calculated with or without clinical variables for significant cancer. RESULTS The frequency of significant cancer in men with negative vs positive magnetic resonance imaging was 9% to 13% vs 43% to 50% in the low risk group and 47% to 51% vs 68% to 71% in the high risk group. In men at low risk with negative magnetic resonance imaging prostate volume was the only significant predictor of significant cancer. In the low risk group the negative predictive value for significant cancer of a combination of positive magnetic resonance imaging and lower prostate volume (less than 33 ml) was 93.7% to 97.5%. CONCLUSIONS Pre-biopsy multiparametric magnetic resonance imaging along with prostate volume decreases the number of initial prostate biopsies by discriminating between significant cancer and other cancer in men with prostate specific antigen less than 10 ng/ml and normal digital rectal examination.

Direct comparison between transrectal and transperineal extended prostate biopsy for the detection of cancer

Aim:  To establish whether extended transrectal (TR) and extended transperineal (TP) biopsies are equivalent in detecting prostate cancer.

New three-dimensional head-mounted display system, TMDU-S-3D system, for minimally invasive surgery application: Procedures for gasless single-port radical nephrectomy

We present an application of a new three‐dimensional head‐mounted display system that combines a high‐definition three‐dimensional organic electroluminescent head‐mounted display with a high‐definition three‐dimensional endoscope to minimally invasive surgery, using gasless single‐port radical nephrectomy procedures as a model. This system presents the surgeon with a higher quality of magnified three‐dimensional imagery in front of the eyes regardless of head position, and simultaneously allows direct vision by moving the angle of sight downward. It is also significantly less expensive than the current robotic surgery system. While carrying out gasless single‐port radical nephrectomy, the system provided the surgeon with excellent three‐dimensional imagery of the operative field, direct vision of the outside and inside of the patient, and depth perception and tactile feedback through the devices. All four nephrectomies were safely completed within the operative time, blood loss was within usual limits and there were no complications. The display was light enough to comfortably be worn for a long operative time. Our experiences show that the three‐dimensional head‐mounted display system might facilitate maneuverability and safety in minimally invasive procedures, without prohibitive cost, and thus might mitigate the drawbacks of other three‐dimensional vision systems. Because of the potential benefits that this system offers, it deserves further refinements of its role in various minimally invasive surgeries.

Prognostic Impact of C-reactive Protein for Determining Overall Survival of Patients With Castration-resistant Prostate Cancer Treated With Docetaxel

OBJECTIVE To verify the prognostic impact of C-reactive protein (CRP) for patients with castration-resistant prostate cancer (CRPC) treated with docetaxel in a single institution. METHODS A group of 80 consecutive patients with CRPC were treated with docetaxel in our institution from January 2005 to May 2010. The patients received 75 mg/m(2) of docetaxel intravenously every 3 weeks. The prognostic value of all covariables, including CRP, was assessed using the Cox proportional hazard model. Risk stratification for overall survival was described from the results of the multivariable analysis. RESULTS The median survival period for all patients was 14.5 months. The multivariable analysis showed that CRP and hemoglobin levels were independent prognostic factors for overall survival. Based on the presence of an elevated CRP concentration and/or a low hemoglobin level, all patients were stratified into 3 risk groups: those with no risk factors (low-risk group), those with 1 risk factor (intermediate-risk group), and those with 2 risk factors (high-risk group). The overall survival curves were clearly tiered according to the risk groups, with the 1-year overall survival rates being 86.3%, 60.5%, and 23.0% for the low-, intermediate-, and high-risk groups, respectively (P <.001). CONCLUSION CRP is an independent prognostic factor for overall survival of patients with CRPC treated with docetaxel. Risk stratification based on CRP and hemoglobin could be helpful for estimating the overall survival.

Characteristics and clinical significance of prostate cancers missed by initial transrectal 12-core biopsy

Study Type – Diagnostic (exploratory cohort)

Simple and effective local anesthesia for transperineal extended prostate biopsy: Application to three‐dimensional 26‐core biopsy

Abstract:  We developed a local anesthetic procedure for three‐dimensional 26‐core prostate biopsy (3D26PBx), a combination of transperineal 14‐core biopsy (TP14PBx) and transrectal 12‐core biopsy (TR12PBx). At first, a periapical triangle, confined by the levator ani, the rhabdosphincter and the external anal sphincter muscle, was made visible by transrectal ultrasound. After administration of 1 mL of 1%‐lidocaine into the midline perineal skin 1.5 cm above the anus, we inserted a spinal needle toward the periapical triangle for injection of 1.5–2.0 mL of 1%‐lidocaine and performed the TP14PBx. After administration of the periprostatic nerve block with 10 mL of 1%‐lidocaine, we performed the TR12PBx. The efficacy of the procedure was evaluated prospectively in 45 consecutive men undergoing the 3D26PBx. The 3D26PBx was completed with just local anesthesia in all patients. The pain levels, assessed by an 11‐point visual analog scale, were not different between the TP14PBx and the TR12PBx.

Roles of attenuated neuronal nitric-oxide synthase protein expression and accelerated arginase activity in impairing neurogenic relaxation of corpus cavernosum in aged rabbits.

To investigate whether changes in neuronal nitric oxide synthase (nNOS) protein expression and arginase activity are implicated in impairing the neurogenic cavernosal relaxation in aged rabbits, as NO is important in the neurogenic relaxation of corpus cavernosum during the erectile state.