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Background: The treatment landscape for men with metastatic hormone-naïve prostate cancer (mHNPC) has dramatically changed with the approval of next-generation anti-androgen drugs. We compared the treatment efficacy of abiraterone with that of combined androgen blockade (CAB) therapy and androgen deprivation therapy (ADT) alone in men with high-risk mHNPC. Methods: In total, 146 Japanese men with high-risk mHNPC were retrospectively analyzed. As initial hormonal therapy, 30, 83, and 33 men were treated with ADT plus abiraterone (ABI group), ADT plus bicalutamide (CAB group), and ADT alone (ADT group), respectively. Treatment efficacy was compared using time to castration resistance (TTCR) and prostate-specific antigen (PSA) response among the groups. Propensity score matching analysis was also performed to adjust for baseline differences. Results: The median (95% confidence interval [CI]) TTCR in the ABI, CAB, and ADT groups were not reached, 10.7 (7.6–13.8) months and 11.0 (7.9–12.4) months, respectively, and it was significantly longer in the ABI group than in the other groups (p = 0.0012, p = 0.0008). In propensity score matching analysis, the median TTCR was also significantly longer in the ABI group than in the other groups (hazard ratio [HR], 0.47; 95% CI, 0.22–0.98; p = 0.010; HR, 0.32; 95% CI, 0.12–0.85; p = 0.004). The number of men who achieved PSA levels ≤0.2 ng/mL after propensity score matching were significantly higher in the ABI group than in the other groups. Conclusions: Our results provide important evidence regarding the superiority of abiraterone over CAB therapy and ADT alone for initial treatment for men with newly diagnosed mHNPC. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the impact of a novel biopsy instrument that extends the length of the side‐notch on the detection of prostate cancer in transrectal needle biopsy. Methods: We collaborated with a biopsy needle manufacturer and developed a novel biopsy instrument (PRIMECUT II long‐notch type) with a 25‐mm side‐notch length and 28‐mm stroke length to take longer tissue cores. The sampled core length, cancer detection rate, pain and complications of 489 patients who underwent transrectal biopsy using the long‐notch needle were compared with those of 469 patients who underwent biopsy using a normal instrument with a 19‐mm side‐notch length and 22‐mm stroke length. Results: The mean length of tissue taken by the long‐notch needle was significantly longer than that of tissue taken by the normal‐notch needle (16.3 vs 22.4 mm, P < 0.001). The overall cancer detection rate was 42.0% for the normal‐notch needle and 51.1% for the long‐notch needle (P = 0.005). In patients with a prostate volume of 20–40 mL, the cancer detection rate for the long‐notch needle was especially higher than that for the normal‐notch needle (74.2% vs 47.5%, P < 0.001). Multivariate analysis showed that the long‐notch needle improved cancer detection significantly (odds ratio 1.702, P < 0.001). There were no differences of pain during biopsy and complication between the two groups. Conclusions: The novel biopsy instrument with a 25‐mm side‐notch can take longer tissue samples safely and has a significantly higher rate of prostate cancer detection in transrectal biopsy. [ABSTRACT FROM AUTHOR]

Background: Introducing a new surgical technology may affect behaviors and attitudes of patients and surgeons about clinical practice. Robot-assisted laparoscopic radical prostatectomy (RALP) was approved in 2012 in Japan. We investigated whether the introduction of this system affected the treatment of organ-confined prostate cancer (PCa) and the use of radical prostatectomy (RP).Methods: We conducted a retrospective multicenter study on 718 patients with clinically determined organ-confined PCa treated at one of three Japanese academic institutions in 2011 (n = 338) or 2013 (n = 380). Two patient groups formed according to the treatment year were compared regarding the clinical characteristics of PCa, whether referred or screened at our hospital, comorbidities and surgical risk, and choice of primary treatment.Results: Distribution of PCa risk was not changed by the introduction of RALP. Use of RP increased by 70% (from 127 to 221 cases, p < 0.0001), whereas the number of those undergoing radiotherapy or androgen deprivation therapy decreased irrespective of the disease risk of PCa. Increased use of RP (from 34 to 100 cases) for intermediate- or high-risk PCa patients with mild perioperative risk (American Society of Anesthesiologists score 2) accounted for 70% of the total RP increase, whereas the number of low- or very low-risk PCa patients with high comorbidity scores (Charlson Index ≥ 4) increased from 8 to 25 cases, accounting for 18%. Use of expectant management (active surveillance, watchful waiting) in very low-risk PCa patients was 15% in 2011 and 12% in 2013 (p = 0.791).Conclusions: Introduction of a robotic surgical system had little effect on the risk distribution of PCa. Use of RP increased, apparently due to increased indications in patients who are candidates for RP but have mild perioperative risk. Although small, there was an increase in the number of RPs performed on patients with severe comorbidities but with low-risk or very low-risk PCa. [ABSTRACT FROM AUTHOR]

Objectives To compare various methods for measuring tumor extent in prostate biopsy specimens to identify small-volume prostate cancer. Methods A total of 100 radical prostatectomy specimens were retrospectively analyzed. Receiver operating characteristic analysis was used to compare the abilities of prostate-specific antigen density, and four measures of tumor extent in prostate biopsy specimens - positive core number, greatest percentage of cancer in a single core, greatest length of cancer in cores and total length of cancer in cores - to identify small volume prostate cancer. Four definitions of insignificant cancer volume were used in this analysis: index and total tumor volume <0.5 mL, index tumor volume <1.3 mL and total tumor volume <2.5 mL. Multivariate analysis was also used to evaluate variables for predicting small-volume prostate cancer. Results Total length of cancer in cores had the highest areas under the curve of all the measures defining small-volume prostate cancer: index tumor volume <0.5 mL (0.855), total tumor volume <0.5 mL (0.877), index tumor volume <1.3 mL (0.784) and total tumor volume <2.5 mL (0.818). On multivariate analysis total length of cancer in cores was an independent predictive factor for prostate cancers with index tumor volume <0.5 mL ( P < 0.001), <1.3 mL ( P < 0.001) and total tumor volume <0.5 mL ( P < 0.001), respectively. Conclusion Our data suggest that total length of cancer in cores is the optimal measure of tumor extent in prostate biopsy specimens for identifying small-volume prostate cancer. [ABSTRACT FROM AUTHOR]

Objectives To compare perioperative, oncological and functional outcomes of robot-assisted radical prostatectomy between experienced and novice open radical prostatectomy surgeons in a laparoscopically naïve center with a limited caseload. Methods Six surgeons carried out robot-assisted radical prostatectomy in 154 patients, which were divided into the following three groups: group 1 ( n = 90), including patients operated on by a surgeon with experience in both open radical prostatectomy and robot-assisted radical prostatectomy; group 2 ( n = 36), including patients operated on by two surgeons with experience in open radical prostatectomy only; and group 3 ( n = 28), including patients operated on by three surgeons with limited experience in both open radical prostatectomy or robot-assisted radical prostatectomy. Results Groups 2 and 3 did not differ significantly in their median values of external blood loss ( P = 0.165) or console time ( P = 0.103). Positive surgical margin rates for pT2 patients were also similar in these two groups: 21.2% (7/33) in group 2 and 22.7% (5/22) in group 3 ( P = 0.894). Kaplan-Meier analysis showed that 12 months after robot-assisted radical prostatectomy the prostate-specific antigen-free rate for pT2 patients was 96.0% in group 2 and 100% in group 3, but the pad-free continence rate was just 91.0% in group 1, 88.0% in group 2 and 75.5% in group 3 (group 1 vs group 3, P = 0.037; group 2 vs group 3, P = 0.239). The major complication rate after robot-assisted radical prostatectomy was 3.3% (3/90) in group 1, 11.1% (4/36) in group 2 and 17.9% (5/28) in group 3 (group 1 vs group 3, P = 0.008; group 2 vs group 3; P = 0.441). Conclusions Robot-assisted radical prostatectomy offers satisfactory postoperative outcomes even when carried out by surgeons with limited experience in open radical prostatectomy. [ABSTRACT FROM AUTHOR]

Objective To investigate whether transrectal needle biopsy can be optimised to detect nearly all prostate cancer with a tumour volume ( TV) of ≥0.5 mL., Materials and Methods Retrospectively analysed 109 whole-mounted and entirely submitted radical prostatectomy specimens with prostate cancer., All tumours in each prostate were outlined on whole-mount slides and digitally scanned to produce tumour maps. Tumour map images were exported to three-dimensional (3 D) slicer software (http://www.slicer.org) to develop a 3 D-prostate cancer model., In all, 20 transrectal biopsy schemes involving two to 40 cores and two to six anteriorly directed biopsy ( ADBx) cores (including transition zone, TZ) were simulated, as well as models with various biopsy cutting lengths., Detection rates for tumours of different volumes were determined for the various biopsy simulation schemes., Results In 109 prostates, 800 tumours were detected, 90 with a TV of ≥0.5 mL (mean TV 0.24 mL)., Detection rate for tumours with a TV of ≥0.5 mL plateaued at 77% (69/90) using a 12-core (3 × 4) scheme, standard 17-mm biopsy cutting length without ADBx cores. In all, 20 of 21 (95%) tumours with a TV of ≥0.5 mL not detected by this scheme originated in the anterior peripheral zone or TZ., Increasing the biopsy cutting length and depth/number of ADBx cores improved the detection rate for tumours with a TVof ≥0.5 mL in the 12-core scheme., Using a 22-mm cutting length and a 12-core scheme with additional volume-adjusted ADBx cores, 100% of ≥0.5 mL tumours in prostates ≤ 50 mL in volume and 94.7% of ≥0.5 mL tumours in prostates > 50 mL in volume were detected., Conclusions Our 3 D-prostate cancer model analysis suggests that nearly all prostate cancers with a TV of ≥0.5 mL can be detected by 14-18 transrectal needle-biopsy cores., Using longer biopsy cutting lengths and increasing the depth and number of ADBx cores (including TZ) according to prostate volume are necessary as well. [ABSTRACT FROM AUTHOR]

Objectives: To develop and assess a new nomogram incorporating pre-biopsy clinical data to predict significant prostate cancer in Japanese men with a serum prostate-specific antigen (PSA) level of less than 10 ng/mL. Methods: We collected pre-biopsy data from 620 men with a serum total PSA of less than 10 ng/mL. They included 491 men with a negative biopsy and 129 men who were confirmed to have histological prostate cancer and subsequently underwent radical prostatectomy. Clinically significant tumors were defined as those with a tumor volume larger than 0.5 mL and/or a Gleason score of 7 or more. Results: One hundred and seven prostatectomy patients had clinically significant cancers. Stepwise multivariate logistic regression analysis showed that digital rectal examination findings, PSA adjusted for transition zone volume and free-to-total PSA ratio were the significant independent predictors of significant cancers ( P < 0.0001). Using these pre-biopsy independent factors, a nomogram was developed to predict significant cancers. According to a receiver operating characteristics analysis, the nomogram showed an area under the curve of 0.831. Conclusion: This represents the first nomogram to predict the probability of clinically significant cancers before biopsy. This tool is most likely to be useful in the management of patients with moderate to elevated PSA. [ABSTRACT FROM AUTHOR]

The clinical application of volume estimation by 3-D ultrasound has recently gained much attention. However, there have been no reports evaluating the prostate volume by 3-D transrectal ultrasound (TRUS) before transurethral resection of the prostate (TURP). The purpose of the present study was to evaluate the value of 3-D TRUS for prediction of prostate morphology and resected weight before TURP and to investigate whether 3-D TRUS is a more useful examination than 2D TRUS in patients with benign prostatic hyperplasia (BPH).Transurethral resection of the prostate was performed in 23 patients with BPH. We evaluated the prostate morphology and measured both the volumes of the whole prostate and the transition zone using 2-D and 3-D TRUS, respectively. The actual resected weight was recorded and compared with the volume of the whole prostate and that of the transition zone measured by 2D and 3-D TRUS.The volume of the transition zone measured by 3-D TRUS correlated most strongly with the resected weight (r = 0.84). A large median lobe was seen in three patients in whom the transition zone volume measured by 2-D TRUS was considerably larger than the resected weight. However, overestimation in the three patients decreased by the use of 3-D TRUS.It was concluded that 3-D TRUS was equal or superior to 2-D TRUS in prediction of the resected weight and 3-D TRUS offers better information as a diagnostic tool before TURP. [ABSTRACT FROM AUTHOR]

Background Gemcitabine/Cisplatin (GC) therapy is first-line chemotherapy for advanced urothelial carcinoma (UC). The Renal Impairment Clinical Practice Guidelines 2016 suggest that, Cisplatin (CDDP) may be administered by up to 50% of standard dose for patients with hemodialysis (HD) because of the renal toxicity. The evidence is, however, scanty to evaluate safety. We report a case of GC therapy for a UC patient undergoing HD. Patient A 80-years old male with bilateral papillary UC had a total renal ureteral resection and underwent HD. Two courses of adjuvant GC therapy were to be performed. The standard dose of Gemcitabine (GEM) and 50% of standard dose of CDDP were administered on the same day based on CDDP and GEM interview form and literature for HD patients. HD started 6 hours after GEM administration and 1 hour after CDDP administration. The volume of infusion was 600 mL; diuretics were not used. Side effects were evaluated according to Common Terminology Criteria for Adverse Events v4.0. Results In first course, Grade 4 side effects were observed: leukopenia, neutropenia and thrombocytopenia. They were treated by granulocyte-colony stimulating factor (G-CSF) administration and platelet transfusion. No febrile neutropenia was observed. Because the second course was administered without reducing the doses, G-CSF was prophylactically administered, and the Grade 4 side effects were reduced to Grade 3. No relapse was observed by now. Conclusion We could performed GC therapy safety for a patient with advanced UC undergoing HD by managing adverse event adequately. [ABSTRACT FROM AUTHOR]

Gemcitabine/Cisplatin (GC) therapy is first-line chemotherapy for advanced urothelial carcinoma (UC). The Renal Impairment Clinical Practice Guidelines 2016 suggest that, Cisplatin (CDDP) may be administered by up to 50% of standard dose for patients with hemodialysis (HD) because of the renal toxicity. The evidence is, however, scanty to evaluate safety. We report a case of GC therapy for a UC patient undergoing HD. A 80-years old male with bilateral papillary UC had a total renal ureteral resection and underwent HD. Two courses of adjuvant GC therapy were to be performed. The standard dose of Gemcitabine (GEM) and 50% of standard dose of CDDP were administered on the same day based on CDDP and GEM interview form and literature for HD patients. HD started 6 hours after GEM administration and 1 hour after CDDP administration. The volume of infusion was 600 mL; diuretics were not used. Side effects were evaluated according to Common Terminology Criteria for Adverse Events v4.0. In first course, Grade 4 side effects were observed: leukopenia, neutropenia and thrombocytopenia. They were treated by granulocyte-colony stimulating factor (G-CSF) administration and platelet transfusion. No febrile neutropenia was observed. Because the second course was administered without reducing the doses, G-CSF was prophylactically administered, and the Grade 4 side effects were reduced to Grade 3. No relapse was observed by now. We could performed GC therapy safety for a patient with advanced UC undergoing HD by managing adverse event adequately. [ABSTRACT FROM AUTHOR]

Objectives To investigate oncological outcomes and prognostic factors in patients with upper tract urothelial carcinoma ( UTUC) who experienced disease recurrence after radical nephroureterectomy ( RNU)., Few studies have focused on the clinical courses of patients who experienced disease recurrence after RNU., Patients and Methods A total of 204 UTUC patients who experienced disease recurrence from a retrospective multi-institutional cohort were included in the present study., Associated patient outcomes were analyzed using multivariate analysis., Results The mean time from RNU to first disease recurrence was 15.0 months and ≈90% of patients experienced disease recurrence within the first 3 years after RNU., During a median follow-up of 8.1 month after disease recurrence, 165 patients died from UTUC and five patients died from other causes. In the 204 cohorts, 1- and 3-year cancer-specific survival rates were 40.2% and 9.7%, respectively, and 1- and 3-year overall survival rates were 39.5% and 9.4%, respectively., After disease recurrence, 132 patients underwent systemic chemotherapy, and a subgroup analysis of patients who underwent systemic chemotherapy multivariate analysis showed that performance status, the presence of liver metastasis and the number of recurrence sites were independently prognostic of cancer-specific and overall survival after relapsing., According to three significant variables, 1- and 3-year cancer-specific survival rates were 72.7% and 20.8% in patients with no risk factors, 46.5% and 7.5% in patients with one risk factor, and 26.4% and 4.4% in patients with two or three risk factors, respectively ( P < 0.001)., Conclusions Most patients died from UTUC within 3 years, even though systemic chemotherapies were administered after relapsing., Multivariate analysis showed that performance status, the presence of liver metastasis and the number of recurrence sites were independently related to poor survival after systemic chemotherapy. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the relationship between serum interleukin (IL)-6 and cachexia in patients with prostate cancer. Methods: Serum levels of IL-6, total protein, albumin, total cholesterol, and hemoglobin concentration were determined in 164 blood samples from patients with prostate cancer. The body mass index and performance status were also determined. Results: The serum total protein, albumin, and cholesterol levels, hemoglobin levels, and body mass index of the patients whose serum IL-6 level was 7 pg/mL or greater were significantly lower (P <0.05) than the corresponding values in patients with a serum IL-6 level of less than 7 pg/mL. The serum IL-6 level of patients with a serum albumin level of less than 3.5 g/dL, serum total protein level of less than 7.0 g/dL, serum total cholesterol level of less than 180 mg/dL, hemoglobin level of less than 11.0 g/dL, and body mass index of less than 21 kg/m2 were significantly greater (P <0.05) than the values in their respective counterparts. A significant correlation was found between the elevation of serum IL-6 and performance status (P <0.05). The mortality rate of patients with greater serum IL-6 levels was significantly greater than that of those with lower serum IL-6 levels in patients with untreated disease, patients in remission, and patients with relapse (all P <0.05). Conclusions: These findings suggest that IL-6 may be one of the factors contributing to the complex syndrome of cachexia in patients with prostate cancer (all P <0.05). [Copyright &y& Elsevier]

Management of advanced hormone‐naïve prostate cancer (HNPC) is a critical public health issue. Useful prognostic markers are thus needed to select patients who will benefit from recently introduced upfront therapies. p16 expression is an adverse prognostic marker in prostate cancer. The present study aimed to determine whether p16 expression would serve as an adverse prognostic marker in advanced HNPC. A total of 79 patients diagnosed by needle biopsy with adenocarcinoma Gleason score ≥8 between 2010 and 2013 at Aichi Medical University were included in this study. The median patient age was 73 (range 52–87) years. The median follow‐up was 62 months (range 2–98). Fourteen patients had p16‐positive samples. Fifteen patients died from prostate cancer, 10 of whom were in the p16‐positive group. p16 positivity was associated with clinical T stage (P < 0.001), presence of IDC‐P (P < 0.001), distant metastasis (P < 0.001) and lymph node metastasis (P < 0.001). These results indicate that p16 expression is associated with adverse prognostic factor of prostate cancer and suggest that p16 expression may provide useful information for treatment planning and identifying suitable candidates for upfront chemotherapy or androgen receptor axis‐targeted therapy. [ABSTRACT FROM AUTHOR]

Prostatic calculi are classified into two types, endogenous and exogenous calculi, based on their origin. Endogenous calculi are commonly observed in elderly men; however, exogenous prostatic calculi are extremely rare. We report here the case of a 51-year-old man who suffered incontinence and pollakiuria with a giant exogenous prostatic calculus almost completely replacing the prostatic tissue. X-rays and computed tomography demonstrated a large calculus of 65 × 58 mm in the small pelvic cavity. The patient underwent a transurethral lithotripsy with a holmium-YAG laser and a total of 85 g of disintegrated stones was retrieved and chemical stone analysis revealed the presence of magnesium ammonium phosphate. The incontinence improved and the voiding volume increased dramatically, and no stone recurrence in the prostatic fossa occurred at the 2 years follow-up. The etiology of this stone formation seemed to be based on some exogenous pathways combined with urinary stasis and chronic urinary infection due to compression fracture of the lumbar vertebra. [ABSTRACT FROM AUTHOR]

Flomoxef is used to treat bacterial prostatitis; however, its prostatic pharmacokinetics have not been fully clarified. Flomoxef (500 or 1000 mg) was administered to patients with benign prostatic hypertrophy (n = 54). After a 0.5-h infusion, venous blood samples were drawn at time points of 0.5–5 h, and prostate tissue samples were collected at time points of 0.5–1.5 h during transurethral resection of the prostate. The drug concentrations in plasma and prostate tissue were analyzed pharmacokinetically and used for a stochastic simulation to predict the probability of attaining pharmacodynamic target in prostate tissue. Showing dose linearity in the prostatic pharmacokinetics, flomoxef rapidly penetrated into prostate tissue, with a prostate/plasma ratio of 0.48–0.50 (maximum drug concentration) and 0.42–0.55 (area under the drug concentration-time curve). Against the tested populations of Escherichia coli , Klebsiella and Proteus species isolates, 0.5-h infusion of 1000 mg three times daily achieved a ≥90% expected probability of attaining the bactericidal target (70% of the time above the minimum inhibitory concentration [MIC]) in prostate tissue. The site-specific pharmacodynamic-based breakpoint (the highest MIC at which the target-attainment probability in prostate tissue was >90%) values were 0.25 mg/L (MIC for 90th percentile of E. coli and Klebsiella species) for 500 mg four times daily and 0.5 mg/L (MIC 90 of Proteus species) for 1000 mg four times daily. These results help to fully characterize the prostatic pharmacokinetics of flomoxef, while also helping to rationalize and optimize the dosing regimens for prostatitis based on site-specific pharmacodynamic target attainment. [ABSTRACT FROM AUTHOR]

The present study examined the clinical pharmacokinetics of pazufloxacin in prostate tissue and estimated the probability of target attainment for tissue-specific pharmacodynamic goals related to treating prostatitis using various intravenous dosing regimens. Patients with prostatic hypertrophy received prophylactic infusions of pazufloxacin (500 mg, n = 23; 1000 mg, n = 25) for 0.5 h prior to transurethral prostate resection. Drug concentrations in plasma (0.5–5 h) and prostate tissue (0.5–1.5 h) were measured by high-performance liquid chromatography and used for subsequent noncompartmental and three-compartmental analysis. Monte Carlo simulation was performed to evaluate the probability of target attainment of a specific minimum inhibitory concentration (MIC) in prostate tissue: the proportion that achieved both area under the drug concentration over time curve (AUC)/MIC = 100 and maximum concentration (C max )/MIC = 8. Prostatic penetration of pazufloxacin was good with mean C max ratios (prostate tissue/plasma) of 0.82–0.99 and for AUC, 0.80–0.98. The probability of reaching target MIC concentrations in prostate tissue was more than 90% for dosing schedules of 0.25 mg/L for 500 mg every 24 h (500 mg daily), 0.5 mg/L for 500 mg every 12 h (1000 mg daily), 1 mg/L for 1000 mg every 24 h (1000 mg daily), and 2 mg/L for 1000 mg every 12 h (2000 mg daily). Importantly, the 2000 mg daily regimen of pazufloxacin produced a profile sufficient to have an antibacterial effect in prostate tissue against clinical isolates of Escherichia coli and Klebsiella pneumonia with MIC values less than 2 mg/L. [ABSTRACT FROM AUTHOR]

Objectives To identify predictive factors for the severity of epididymitis and to develop an algorithm guiding decisions on how to manage patients with this disease. Methods A retrospective study was carried out on 160 epididymitis patients at Keio University Hospital. We classified cases into severe and non-severe groups, and compared clinical findings at the first visit. Based on statistical analyses, we developed an algorithm for predicting severe cases. We validated the algorithm by applying it to an external cohort of 96 patients at Tokyo Medical Center. The efficacy of the algorithm was investigated by a decision curve analysis. Results A total of 19 patients (11.9%) had severe epididymitis. Patient characteristics including older age, previous history of diabetes mellitus and fever, as well as laboratory data including a higher white blood cell count, C-reactive protein level and blood urea nitrogen level were independently associated with severity. A predictive algorithm was created with the ability to classify epididymitis cases into three risk groups. In the Keio University Hospital cohort, 100%, 23.5%, and 3.4% of cases in the high-, intermediate-, and low-risk groups, respectively, became severe. The specificity of the algorithm for predicting severe epididymitis proved to be 100% in the Keio University Hospital cohort and 98.8% in the Tokyo Medical Center cohort. The decision curve analysis also showed the high efficacy of the algorithm. Conclusions This algorithm might aid in decision-making for the clinical management of acute epididymitis. [ABSTRACT FROM AUTHOR]

Objectives To investigate the impact of perioperative plasma fibrinogen level as a biomarker of oncological outcome in localised renal cell carcinoma ( RCC). Patients and methods We consecutively identified 601 patients with localised RCC who underwent curative surgery at a single institution. Subsequent disease recurrence and cancer-specific survival ( CSS) were assessed using the Kaplan-Meier method. To evaluate the independent prognostic impact of plasma fibrinogen level, multivariate analysis was performed for these outcomes. Results Using the defined threshold level of preoperative plasma fibrinogen of ≥420 mg/ dL as elevated, we found 56 patients (9.3%) with an elevated plasma fibrinogen level preoperatively. In Kaplan-Meier analysis, there was a significant difference in disease-free survival and CSS rates between patients with and without preoperative plasma fibrinogen levels of ≥420 mg/ dL. Multivariate analysis showed that elevated preoperative plasma fibrinogen level was an independent predictor of subsequent disease recurrence and cancer-specific mortality. In a subgroup analysis of the elevated preoperative plasma fibrinogen level group, postoperative normalisation of plasma fibrinogen level was significantly associated with CSS, showing that patients with non-normalised plasma fibrinogen levels tended to have a higher incidence of cancer-specific mortality after surgery. Conclusion Patients with elevated preoperative plasma fibrinogen levels could be significantly predicted to have subsequent tumour metastasis and cancer-specific mortality, while there was a significant difference in CSS between patients in the normalised and non-normalised postoperative plasma fibrinogen groups. While these are hypothesis generating results, plasma fibrinogen levels may be a useful biomarker due to its low cost and ease of assessment. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the penetration of PIPC–TAZ into human prostate, and to assess effectiveness of PIPC–TAZ against prostatitis by evaluating site-specific PK–PD. Patients with prostatic hypertrophy ( n = 47) prophylactically received a 0.5 h infusion of PIPC–TAZ (8:1.2–0.25 g or 4–0.5 g) before transurethral resection of the prostate. PIPC–TAZ concentrations in plasma (0.5–5 h) and prostate tissue (0.5–1.5 h) were analyzed with a three-compartment PK model. The estimated model parameters were, then used to estimate the drug exposure time above the minimum inhibitory concentration for bacteria ( T > MIC, the PD indicator for antibacterial effects) in prostate tissue for six PIPC–TAZ regimens (2.25 or 4.5 g; once, twice, three times or four times daily; 0.5 h infusions). Prostate tissue/plasma ratio of PIPC was about 36% both for the maximum drug concentration ( C max ) and the area under the drug concentration–time curve (AUC). Against MIC distributions for isolates of Escherichia coli , Klebsiella species and Proteus species, regimens of 4.5 g twice daily and 2.25 g three times daily achieved a >90% probability of attaining the bacteriostatic target for PIPC (30% T > MIC) in prostate tissue; regimens of 4.5 g three times daily and 2.25 g four times daily achieved a >90% probability of attaining the bactericidal target for PIPC (50% T > MIC) in prostate tissue. However, against Pseudomonas aeruginosa isolates, none of the tested regimens achieved a >90% probability. PIPC–TAZ is appropriate for the treatment of prostatitis from the site-specific PK–PD perspective. [ABSTRACT FROM AUTHOR]

Abstract: Background and objective: Few studies have addressed the predictive value of positive urine cytology for prognosis in patients with upper tract urothelial carcinoma (UTUC). We investigated whether the status of preoperative urine cytology could provide additional prognostic information following radical nephroureterectomy (RNU). Materials and methods: The study included 474 patients with primary nonmetastatic UTUC (pTa-4N0M0) from a retrospective multi-institutional cohort. The median follow-up period was 35 months. Associations between the status of urine cytologic evaluation and outcomes were analyzed using multivariate Cox regression models. Urine cytology was evaluated preoperatively using voided samples. Disease recurrence was defined as any relapse in nonbladder lesions and was coded separately from intravesical recurrence. Results: Positive urine cytology was detected in 184 patients (38.8%) preoperatively. Disease recurrence occurred in 127 patients, while intravesical recurrence occurred in 219 patients; 83 patients died of UTUC during follow-up. Kaplan-Meier analysis revealed that only the incidence of intravesical recurrence was significantly associated with the status of urine cytologic evaluation (P = 0.024); the intravesical recurrence-free survival rates at 1 and 3 years following RNU were 61.4% and 46.2% in patients with positive urine cytology and 71.1% and 51.6% in their counterparts, respectively. Multivariate analysis showed that gender (hazard ratio [HR] = 1.74, 95% confidence interval [CI]; 1.28–2.43), tumor multifocality in RNU specimens (HR = 1.64, 95% CI; 1.09–2.47), and positive urine cytology (HR = 1.41, 95% CI; 1.08–1.85) were independent risk factors for subsequent intravesical recurrence. Conclusions: The results showed the prognostic value of positive urine cytology in patients with primary UTUC, and preoperative positive urine cytology may be associated with a significant increase in the prevalence of intravesical recurrence following RNU. [Copyright &y& Elsevier]

Objective To evaluate the suitability of preoperative multiparametric magnetic resonance imaging ( MRI) positivity as a predictor of biochemical recurrence after radical prostatectomy ( RP)., Patients and Methods We reviewed the clinical records of patients who underwent either standard RP or laparoscopic RP between January 2005 and December 2009 at our institution., Patients who received radiotherapy or androgen deprivation therapy before surgery were excluded. A total of 314 patients met the study inclusion criteria., Cox proportional hazard regression models were used for analyses., In accordance with the criteria in the established guidelines, a radiologist scored the probability of the presence of prostate cancer using a five-point scale of diagnostic confidence level. The highest confidence level of any pulse sequence was considered as the evaluation result., Results MRI positivity was significantly associated with a high clinical stage ( cT ≥ 2; P = 0.039), a high positive biopsy core rate (≥0.2; P < 0.001), a high biopsy Gleason score ([ GS] ≥8; P < 0.001) and a high pathological GS (≥8; P = 0.005)., Univariate analysis and multivariate analysis showed that MRI positivity was a prognostic indicator in the analysis that included only preoperative variables and also in the analysis including preoperative and pathological variables., Conclusion Multiparametric MRI positivity can independently predict biochemical recurrence after RP. [ABSTRACT FROM AUTHOR]

Abstract: Background: Few studies have discussed the prognostic impact of serum C-reactive protein (CRP) level in upper tract urothelial carcinoma (UTUC). Objective: To investigate whether the perioperative level of CRP provides additional prognostic information following radical nephroureterectomy (RNU). Design, setting, and participants: A total of 564 patients with UTUC from a retrospective multi-institutional cohort were included. The median follow-up was 32 mo. Intervention: All patients underwent RNU without neoadjuvant chemotherapy, while 106 patients (18.8%) received adjuvant chemotherapy. Outcome measurements and statistical analysis: Associations between perioperative CRP level and outcome were assessed using multivariate analysis. A serum CRP level >0.50mg/dl was defined as elevated. Results and limitations: Preoperative CRP (pre-CRP) level was elevated in 136 patients (24.1%). Multivariate analysis showed that pre-CRP elevation was an independent predictor of subsequent disease recurrence (hazard ratio [HR]: 1.47 for CRP 0.51–2.00; HR: 1.89 for CRP >2.00). Five-year recurrence-free survival rates were 69.2% in patients with pre-CRP levels ≤0.50mg/dl, 54.3% in patients with pre-CRP levels between 0.51 and 2.00mg/dl, and 35.4% in patients with pre-CRP levels >2.00mg/dl (p <0.001). Similar results were found in cancer-specific mortality, showing that pre-CRP elevation was an independent predictor of worse outcome (HR: 1.74 for CRP 0.51–2.00; HR: 2.31 for CRP >2.00). In a subgroup analysis of the elevated pre-CRP group, postoperative normalisation of CRP level was an independent predictor of better outcome. This study is limited by its retrospective nature as well as its heterogeneous group of patients and variable follow-up protocols resulting from the multi-institution design. Conclusions: Serum CRP may become a possible biomarker in UTUC, suggesting that patients with an elevated pre-CRP level could be predicted to have subsequent disease recurrence and cancer-specific mortality, while postoperative normalisation of CRP level was an independent predictor for prognosis. [Copyright &y& Elsevier]

Abstract: Objectives: To evaluate the association of signal transducer and activator of transcription 3 (STAT3) with the invasiveness and aggressiveness of localized prostate cancer. Methods: Paraffin-embedded specimens from 92 patients with clinically localized prostate cancer who underwent radical prostatectomy without neoadjuvant treatment were analyzed by immunohistochemistry using two antibodies: anti-phospho-specific STAT3 (p-STAT3) antibody, which recognized only activated STAT3, and anti-total STAT3 antibody, which recognized both activated and inactivated STAT3. The patients were separated into one of four groups according to the percentage of the cells with positive nuclear staining using a 0 to 3+ scoring system. The associations between the immunostaining and invasiveness and aggressiveness of clinically localized prostate cancer were analyzed. Results: Pathologically, 66 patients (71.7%) had organ-confined disease. Of the 92 tumors examined, 8, 20, 23, and 41 showed staining patterns for p-STAT3 of 0, 1+, 2+, and 3+, respectively. In addition, 0, 3, 2, and 87 tumors showed staining patterns for STAT3 of 0, 1+, 2+, and 3+, respectively. The staining patterns for p-STAT3 correlated significantly with pathologic stage, Gleason score, and extracapsular extension. No significant correlation was found between p-STAT3 immunostaining and microvascular invasion, perineural invasion, or seminal vesicle invasion. Patients with 3+ immunostaining of p-STAT3 had a significantly greater biochemical prostate-specific antigen failure rate than those with 2+ or less immunostaining. Conclusions: Increased p-STAT3 immunoreactivity showed a highly invasive and aggressive potential in patients with localized prostate cancer treated with radical prostatectomy. This suggests that STAT3 signaling contributes to the invasiveness and aggressiveness of prostate cancer. [Copyright &y& Elsevier]

Purpose: The objective of this study was to develop a novel prognostication model in patients with treatment-naïve metastatic renal cell carcinoma (mRCC).Methods: This study included 325 consecutive mRCC patients receiving first-line molecular-targeted therapy at 4 institutions. Potential parameters associated with overall survival (OS) in these patients were investigated to develop a novel stratification model.Results: Median OS of the 325 patients was 38 months. A multivariable analysis of several factors identified independent predictors associated with unfavorable OS as follows: no previous nephrectomy, Karnofsky performance status <80%, albumin (Alb) ≤3.5 g/dl, C-reactive protein (CRP) >0.5 mg/dl and neutrophil-to-lymphocyte ratio (NLR) >3. Of these 5 independent OS predictors, 3 numeric factors were used to develop the ACN (Alb, CRP, and NLR) model by dividing patients into 3 groups according to the positive numbers of these 3 numeric risk factors. Median OS durations were 63, 37, and 11 months in the favorable (n = 105, 32.3%, without risk factors), intermediate (n = 88, 27.1%, with a single risk factor), and poor (n = 132, 40.6%, with multiple risk factors) risk groups, respectively. The ACN model as a prognostication tool was shown to be superior to the Memorial Sloan Kettering Cancer Center (MSKCC) and the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) models by both the concordance index and decision curve analysis.Conclusions: The ACN model could stratify the prognostic risk of mRCC patients receiving first-line targeted therapy more accurately than the MSKCC and IMDC models. [ABSTRACT FROM AUTHOR]

Objectives: We evaluated the impact of discontinuation of first-line (1L) molecular-targeted therapy on prognostic outcomes among patients with metastatic renal cell carcinoma (mRCC).Methods: Study patients with mRCC were treated with 1L molecular-targeted agents at 4 separate institutions. Prognostic outcomes in this patient cohort were analyzed retrospectively based on whether discontinuation of 1L therapy was related to adverse events (AEs) or progression of disease (PD).Results: Of the 201 patients enrolled, 117 patients (58%) and 84 patients (42%) discontinued 1L targeted therapy due to PD and AEs, respectively. Second-line therapy was subsequently provided to 101 (86%) and 66 (79%) of the patients who discontinued 1L therapy secondary to PD or AEs, respectively. Patients who discontinued 1L therapy due to AEs were significantly older than those with PD. The progression-free survival and overall survival from the initiation of 1L targeted therapy were significantly longer in patients who discontinued 1L therapy due to AE than in those who discontinued 1L therapy due to PD. The OS from the initiation of second-line targeted therapy was significantly longer in patients who discontinued 1L therapy due to AE than those with PD. Furthermore, AE as a reason for discontinuation of 1L targeted therapy as opposed to PD was independently associated with longer progression-free survival and OS as determined by multivariate analysis.Conclusions: Our findings suggest that mRCC patients who discontinue 1L therapy due to AEs have a more favorable prognosis than those who discontinue therapy due to PD. [ABSTRACT FROM AUTHOR]

Purpose: The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk model has been designed for prognostification in patients with metastatic renal cell carcinoma (mRCC) treated with targeted therapy. One factor is neutrophil count; however, increasing evidence has suggested the superiority of neutrophil-to-lymphocyte ratio (NLR) for predicting outcome. In this study, we evaluate the prognostic effect of NLR levels on patients with mRCC treated with targeted therapy, and then we compare the predictive accuracy of the IMDC risk model and its modified one by using NLR, instead of neutrophil count.Patients and Method: A total of 277 patients are included for the analysis. All patients underwent targeted therapies and associated outcome are assessed using multivariate analysis.Results: Pretreatment NLR levels are elevated in 30.3% and 23.1% of patients in the first-line and subsequent second-line setting, respectively. Kaplan-Meier curves reveal that elevated pretreatment NLR is significantly associated with poor overall survival (OS) since first-line (P<0.001) and second-line targeted therapy administration (P<0.001). Also, multivariate analyses show that elevated pretreatment NLR is an independent predictor for poor OS since first-line and second-line targeted therapy administration. The addition of NLR to the IMDC risk model, instead of neutrophil count, significantly improves the predictive accuracy for OS, and estimated gain is 1.7% and 6.2% in first-line and second-line targeted therapy, respectively.Conclusion: Changes in NLR levels could be predictive for prognosis in patients with mRCC treated with first-line and second-line targeted therapy. The addition of NLR significantly improves the predictive accuracy of the IMDC risk model in the first-line and subsequent second-line setting. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the prognostic effect of the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model reclassification after targeted therapy administration in metastatic renal cell carcinoma (mRCC).Patients and Method: A total of 245 mRCC patients treated with targeted therapy are included. The IMDC model reclassification is performed at 1 month after treatment induction of both first-line and second-line targeted therapy.Results: Of the 245 patients, 74 (30.2%) are divided into different risk groups by the IMDC model reclassification after first-line targeted therapy, and patients newly classified with intermediate risk tend to have better overall survival than those remaining in the primary poor-risk group (P = 0.018). Of the 119 patients treated with subsequent second-line targeted therapy, 25 (21.0%) are divided into different risk groups by the IMDC model reclassification after second-line targeted therapy, and patients newly classified with poor risk tend to have increased all-cause mortality compared with those remaining in the primary intermediate-risk group (P = 0.007), whereas patients newly classified with intermediate risk tend to have better overall survival than those remaining in the primary poor-risk group (P = 0.034).Conclusion: Approximately a quarter of the mRCC patients are classified into different risk groups of the IMDC model following targeted therapy administration in the first-line and second-line settings. There is a significant difference in overall survival of subgroups after the IMDC model reclassifications. [ABSTRACT FROM AUTHOR]