[A Case of Massive Prostate Abscess Treated by Transperineal Drainage].

The patient was an 81-year-old man who visited a clinic for fever and lower abdominal pain. He was subsequently diagnosed with prostatitis based on computed tomography (CT) findings that showed swelling of the prostate. Despite treatment with antibacterial therapy, his symptoms did not improve significantly. Since the patient also had myelodysplastic syndrome, he was transferred to our hospital and subsequently diagnosed with prostate abscess based on findings on magnetic resonance imaging (MRI). The abscess had spread widely from the dorsal side of the trigone of the bladder to anterior wall of the rectum. Transperineal drainage was performed to preserve the urethral mucosa of the prostatic urethra. Considering the shape of the abscess cavity, one pigtail catheter was placed in the prostate and another was placed transperineally on the dorsal side of the trigone of the bladder. Cystostomy was performed at the same time. Culture of the abscess revealed the presence of Staphylococcus aureus. As there was little exudate from the abscess 9 days after drainage, the pigtail catheter on the dorsal side of the trigone of the bladder was removed following an injection of minocycline into the abscess. CT showed shrinkage of the abscess 4 days later, and the remaining intraprostatic pigtail catheter was removed after an injection of minocycline. The cystostomy pigtail catheter was subsequently removed since the patient was able to urinate smoothly after clamping. MRI confirmed the disappearance of the abscess cavity 2 months later.

Preoperative risk stratification using plasma fibrinogen levels can predict lymphovascular invasion and poor prognosis in patients with upper urinary tract urothelial carcinoma.

It has been previously indicated that preoperative plasma fibrinogen levels can correlate with cancer progression and be used as a useful predictor of lymph node metastasis or its premetastatic status such as lymphovascular invasion (LVI). In the present study, how preoperative plasma fibrinogen levels, considered in conjunction with other clinicopathological factors, can predict the presence of LVI and prognosisin patients with upper urinary tract urothelial carcinoma (UTUC) was examined. Medical records of 145 patients with UTUC who underwent radical nephroureterectomy (RNU) were retrospectively reviewed. The current study evaluated systemic inflammatory response markers including levels of plasma fibrinogen and other clinicopathological factors in orderto determine independent predictors of LVI and prognosis. The Cox proportional hazards model indicated that positive surgical margins and LVI were independent factors for poor cancer-specific survival (CSS) rates and extraurothelial recurrence-free survival (ERFS) rates. In addition, positive cytology, the presence of hydronephrosis and plasma fibrinogen levels were significant preoperative predictors of LVI. Furthermore, patients exhibiting two or more of higher fibrinogen levels (≥400 mg/dl), positive urine cytology and the presence of hydronephrosis were indicated to exhibit worse CSS or ERFS rates compared with patients exhibiting only one of the aforementioned factors or those with none of the three aforementioned factors in the multivariate analysis of the Cox proportional hazards model. In conclusion, hyperfibrinogenemia can be an independent predictor of the presence of LVI, and stratifying preoperative risk using fibrinogen levels, urine cytology and hydronephrosis can serve as the basis for selecting candidates for additional therapy before and/or after RNU in patients with UTUC.

Postoperative C-reactive protein-to-albumin ratio predicts poor prognosis in patients with bladder cancer undergoing radial cystectomy.

The purpose of the present study was to investigate the prognostic value of the postoperative C-reactive protein/albumin ratio (CAR) in patients with bladder cancer undergoing radial cystectomy. The present study retrospectively reviewed 102 patients who underwent radical cystectomy and were followed for ≥6 months postoperatively at our institution, and evaluated clinicopathological factors and laboratory parameters for cancer-specific survival (CSS) and extraurothelial recurrence-free survival (ERFS). Multivariate analysis using the Cox proportional hazards model revealed that only postoperative CAR ≥0.27 [hazard ratio (HR), 3.368; 95% confidence interval (CI), 1.674-6.731; P<0.001] was an independent factor for poor CSS rate. Higher postoperative CAR was also the only significant factor for shortened ERFS time (HR, 2.401; 95% CI, 1.196-4.684; P=0.015). No significant association was identified between postoperative CAR ≥0.27 and any pathological factors or postoperative laboratory markers besides postoperative neutrophil-to-lymphocyte ratio. Furthermore, postoperative CAR (≥0.27) was an independent factor for poor CSS and ERFS rates in 48 patients with advanced pT stage (≥pT3) in the multivariate analysis (P=0.026 and P=0.036, respectively). A higher postoperative CAR value can provide additional information about the possibility of poor CSS and ERFS rates in patients with bladder cancer undergoing radical cystectomy.

[CLINICAL ANALYSIS OF 95 CASES OF PERCUTANEOUS CYSTOSTOMY].

(Introduction) Percutaneous cystostomy is a standard urological procedure; however, very few reports have focused on the many cases of this procedure performed in Japan. We analyzed the background of the procedure and its approach as well as the incidence of its complications at our institution. (Material and methods) We examined 95 patients who underwent percutaneous cystostomy between April 2010 and March 2019. A comparative analysis was conducted for each type of procedure performed. Furthermore, cases that experienced accidental catheter extraction before the first catheter replacement were analyzed, and the three patient groups were compared based on the type of procedure performed and cases that needed another operation. (Result) The indications for cystostomy were urethral stricture (56.3%), neuropathic bladder (13.5%), and prostatic hyperplasia (11.5%). The complications included hemorrhage, peritoneal injury, urinary tract infection, and catheter damage caused by a puncture needle. The overall complication rate was 10.5%. Based on type of the procedure performed, the incidence of hemorrhage was found to be as high as 25% in patients who underwent the procedure using a cannula puncture needle. Accidental catheter extraction before the first catheter replacement occurred most frequently in patients treated with Seldinger technique (17.0%). The rate of complications including accidental catheter extraction ranged from 25.0% to 25.4% among the three groups. (Conclusion) We prefer the Seldinger technique for the first placement of the cystostomy catheter because of its low rate of hemorrhage, but a cannula puncture needle may also be used by using exploratory puncture if vascular damage and accidental catheter extraction are avoided.

Effect of continuous saline bladder irrigation with concomitant single instillation of chemotherapy after transurethral resection on intravesical recurrence in patients with non-muscle-invasive bladder cancer.

A single immediate instillation of chemotherapy following transurethral resection of bladder tumor (TURBT) is effective in preventing intravesical recurrence (IVR) in patients with non-muscle-invasive urothelial bladder carcinoma (NMIBC). However, continuous saline bladder irrigation (CSBI) is also performed with a single instillation of chemotherapy (SIC), but its inhibitory effect on IVR remains unclear. In the present study, the effect of CSBI with concomitant SIC following TUR on IVR was evaluated in patients with NMIBC. A retrospective review of 253 patients who underwent TURBT and were clinically and histologically diagnosed with NMIBC at National Defense Medical College Hospital was performed. Doxorubicin (DXR) was administered to all patients. Methods of DXR administration included a single instillation of DXR (60 mg in 30-40 ml saline) in 34 patients (group A), continuous irrigation of the bladder with saline including DXR (80 mg in 1 liter saline) in 40 patients (group B) and overnight CSBI after a single instillation of DXR in 179 patients (group C). The difference in IVR-free survival rates was compared after adjusting for significant differences in several covariates between the groups by nearest-neighbor propensity score matching. Prior to propensity score matching, it was identified that time to IVR was significantly longer in group A than in groups B and C; however, it was observed that several factors significantly differed among the three groups. By using nearest neighbor matching, 18 pairs were matched between groups A and B and 33 pairs between the groups A and C. No significant difference was identified in any covariates between these two matched group pairsTime to IVR was significantly longer in the matched group A than in the matched groups B and C (P=0.0255 and P=0.0023, respectively). In conclusion, SIC alone could provide a higher IVR-free survival rate than CSBI with DXR or CSBI with SIC.

Chronic kidney disease and positive surgical margins as prognosticators for upper urinary tract urothelial carcinoma patients undergoing radical nephroureterectomy.

Chronic kidney disease (CKD) is a common condition among elderly patients and has been reported to be a biomarker for the presence of malignant disease. In addition, unfavorable outcomes for patients with upper tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy can be due to independent clinical factors. Therefore, the present study analyzed the clinicopathological data of patients with UTUC, who underwent radical nephroureterectomy at our institution, to clarify whether preoperative CKD and other factors are independent predictors of the shorter disease-specific and/or recurrence-free survival time of these patients. A retrospective review of 187 patients who underwent radical nephroureterectomy was conducted, and patients were followed for at least 3 months postoperatively. The clinicopathological factors that are thought to have potentially significant roles in the progression and metastasis of malignant tumors and for disease-specific and recurrence-free survival were evaluated. Positive surgical margins and an estimation of the glomerular filtration rate (eGFR) of <60 were independent factors for the shorter disease-specific survival time in multivariate analysis with Cox's proportional hazards model [hazard ratio (HR), 2.401: 95% confidence interval (CI), 1.044-5.255; and HR, 2.371: 95% CI, 1.024-5.898, respectively]. Another multivariate analysis also revealed that positive surgical margins (HR, 4.477; 95% CI, 2.042-9.469), and preoperative eGFR <60 (HR, 2.362; 95% CI, 1.067-5.592) were independent factors for the worse recurrence-free survival rate in all patients. Patients with UTUC who had eGFR <60 as well as positive surgical margins had significantly shorter time to disease-specific mortality and extraurothelial recurrence. The present study demonstrated that patients with UTUC undergoing radical nephroureterectomy who have CKD as well as positive surgical margins should be carefully followed up postoperatively.

Expression of AR-V7 and ARv567es in Circulating Tumor Cells Correlates with Outcomes to Taxane Therapy in Men with Metastatic Prostate Cancer Treated in TAXYNERGY.

PURPOSE: Biomarkers aiding treatment optimization in metastatic castration-resistant prostate cancer (mCRPC) are scarce. The presence or absence of androgen receptor (AR) splice variants, AR-V7 and ARv567es, in mCRPC patient circulating tumor cells (CTC) may be associated with taxane treatment outcomes.Experimental Design: A novel digital droplet PCR (ddPCR) assay assessed AR-splice variant expression in CTCs from patients receiving docetaxel or cabazitaxel in TAXYNERGY (NCT01718353). Patient outcomes were examined according to AR-splice variant expression, including prostate-specific antigen (PSA)50 response and progression-free survival (PFS). RESULTS: Of the 54 evaluable patients, 36 (67%) were AR-V7+, 42 (78%) were ARv567es+, 29 (54%) were double positive, and 5 (9%) were double negative. PSA50 response rates at any time were numerically higher for AR-V7- versus AR-V7+ (78% vs. 58%; P = 0.23) and for ARv567es- versus ARv567es+ (92% vs. 57%; P = 0.04) patients. When AR-V mRNA status was correlated with change in nuclear AR from cycle 1 day 1 to day 8 (n = 24), AR-V7+ patients (n = 16) had a 0.4% decrease versus a 12.9% and 26.7% decrease in AR-V7-/ARv567es- (n = 3) and AR-V7-/ARv567es+ (n = 5) patients, respectively, suggesting a dominant role for AR-V7 over ARv567es. Median PFS was 12.02 versus 8.48 months for AR-V7- versus AR-V7+ (HR = 0.38; P = 0.01), and 12.71 versus 7.29 months for ARv567es- versus ARv567es+ (HR = 0.37; P = 0.02). For AR-V7+, AR-V7-/ARv567es+, and AR-V7-/ARv567es- patients, median PFS was 8.48, 11.17, and 16.62 months, respectively (P = 0.0013 for trend). CONCLUSIONS: Although detection of both CTC-specific AR-V7 and ARv567es by ddPCR influenced taxane outcomes, AR-V7 primarily mediated the prognostic impact. The absence of both variants was associated with the best response and PFS with taxane treatment.See related commentary by Dehm et al., p. 1696.

Impact of body mass index on clinicopathological outcomes in patients with renal cell carcinoma without anorexia-cachexia syndrome.

Although obesity defined by a high body mass index (BMI) is generally associated with increased risk of renal cell carcinoma (RCC), low BMI has paradoxically been associated with increased tumor aggressiveness and poor prognosis. As anorexia-cachexia syndrome (ACS) is associated with decreased BMI and is frequently observed in patients with advanced RCC, the present study investigated the association of BMI with tumor aggressiveness and prognosis in RCC in relation to ACS. The association of BMI with clinicopathological parameters was analyzed in 503 consecutive patients who underwent surgery for RCC. Kaplan-Meier curves and rates of overall survival (OS) stratified by BMI were also compared in relation to the presence or absence of ACS, defined as the presence of anorexia or malaise, and/or weight loss and/or hypoalbuminemia. Low BMI was significantly associated with high-grade tumors (P=0.0027) and the presence of distant metastasis (P=0.0025), and patients with a lower BMI had significantly shorter OS than those with a higher BMI (P=0.0441). Patients with ACS had a significantly lower BMI (mean, 21.5 kg/m2) than those without ACS (mean, 23.5 kg/m2; P<0.0001) and had significantly shorter OS than those without ACS (P<0.0001). On multivariate analysis, ACS was an independent predictor of short OS [P=0.0089; hazard ratio (HR), 2.21; 95% confidence interval (CI), 1.22-3.92] and short cancer-specific survival (P=0.0308; HR, 2.03; 95% CI, 1.07-3.78); however, BMI was not (P=0.5440 and P=0.6804, respectively). In the 413 patients without ACS at initial presentation, BMI was not associated with any clinicopathological parameters or OS (log-rank, P=0.4591). BMI itself was not a predictor of survival in patients without ACS, and the association between low BMI and increased tumor aggressiveness and poor prognosis could be due to ACS.

Clinical implication of ectopic liver lipid accumulation in renal cell carcinoma patients without visceral obesity.

Fatty liver has emerged as a prognostic marker of cancer, so we investigated the impact of ectopic lipid accumulation in liver on the clinical outcome for patients with renal cell carcinoma (RCC). The records of 230 consecutive patients who had undergone surgery for RCC were reviewed, and liver lipid accumulation was estimated from the attenuation in unenhanced preoperative CT images. The median liver CT values of patients with G3 tumors was lower than that of patients with G1-2 tumors (P = 0.0116), that of patients with pT3-4 tumors was lower than that of patients with pT1-2 tumors (P = 0.0336), and that of patients with visceral obesity defined as a visceral fat area ≥ 100 cm2 was lower than that of patients without visceral obesity (P < 0.0001). In patients without visceral obesity the median liver CT values of patients with pT3-4 tumors was lower than that of patients with pT1-2 tumors (P = 0.0401), that of patients with metastasis was lower than that of patients without metastasis (P = 0.026), and fatty liver was associated with shorter overall survival (P = 0.0009). Ectopic lipid accumulation in liver thus seems to be a predictor of aggressive forms of RCC.

Docosahexaenoic acid inhibits the phosphorylation of STAT3 and the growth and invasion of renal cancer cells.

Docosahexaenoic acid (DHA) has a variety of anti-tumor activities. The present study examined the anti-tumor activity of DHA in renal cancer cells and its underlying mechanisms of action. The effects of DHA on the viability and proliferation of the human renal cancer cell lines Caki-1 and 786-O were examined by an MTS assay and cell counting. In addition, cell cycle distribution and cell apoptosis were analyzed by flow cytometry and Annexin V staining, and modulation of cell mobility and invasiveness was assessed by wound healing and Matrigel invasion assays. Effects of DHA on intracellular signaling pathways were also analyzed by western blotting. It was observed that DHA significantly reduced the viability and proliferation of Caki-1 and 786-O cells (P<0.01). Specifically, there were increases in the sub-G1 and G2/M cell populations, as well as the percentages of cells exhibiting Annexin-positive and propidium-iodide-negative staining. In addition, the covered area in a wound and the number of cells invading through a Matrigel chamber decreased when Caki-1 or 786-O cells were treated with DHA. Phosphorylation of epidermal growth factor receptor was also upregulated following DHA treatment, while phosphorylation of signal transducer and activator of transcription 3 and Akt was downregulated. Collectively, these data suggest that DHA may be useful in the treatment of renal cell carcinoma.

STAT3 inhibition by WP1066 suppresses the growth and invasiveness of bladder cancer cells.

Signal transducer and activator of transcription 3 (STAT3) regulates the expression of genes mediating cell survival, proliferation and angiogenesis and is aberrantly activated in various types of malignancies, including bladder cancer. We examined whether it could be a novel therapeutic target for bladder cancer using the STAT3 inhibitor WP1066. In T24 and UMUC-3 bladder cancer cells, 5 µM WP1066 prevented the phosphorylation of STAT3 and 2.5 µM WP1066 decreased cell survival and proliferation significantly (P<0.01). WP1066 also induced apoptosis accompanied by the suppression of the expression of Bcl-2 and Bcl-xL in T24 cells. Moreover, the covered area in a wound and the number of cells invading through a Matrigel chamber decreased significantly (P<0.01) when cells were treated with WP1066. The activities of MMP-2 and MMP-9 were also decreased by treatment with 10 µM WP1066. Our results revealed that using WP1066 to inhibit the STAT3 signaling pathway suppressed the viability and invasiveness of bladder cancer cells effectively and could be a novel therapeutic strategy against bladder cancer.

Clinical outcomes of percutaneous radiofrequency ablation for small renal cancer.

Partial nephrectomy is the treatment of choice for small renal cell carcinoma (RCC) from the perspective of cancer management and renal function. However, when patients with RCC are of advanced age, exhibit severe comorbidities, including cardiovascular and pulmonary diseases, or have hereditary RCC, ablative therapies, including radiofrequency ablation (RFA) and cryoablation are useful treatment options. In the present study, the clinical outcomes of percutaneous RFA for treating small RCC were evaluated. Between December 2005 and March 2015, 40 patients (41 renal tumors in total) underwent RFA and a total of 50 sessions of RFA were performed. The average tumor size was 2.5 cm. A total of 18 tumors were exophytic and 23 were parenchymal. Of the 41 tumors, 85.4% were completely ablated by initial RFA and the rate of complete ablation following reablation for residual viable lesions was 95.1%. Local recurrence-free survival following complete ablation was 84.2% at 3 years. A patient with a 4.7 cm RCC tumor rapidly progressed following four RFA treatments until complete ablation was achieved. The metastasis-free survival rate following initial RFA was 95.7% at 3 years. The RCC-specific survival was 100% (mean follow-up, 38 months). Adverse events occurred in five sessions (10%); however, only 1 patient with arteriovenous fistula required intervention (transarterial embolization). The mean hospital stay following RFA was 3.2 days. The mean decrease in estimated glomerular filtration rate following RFA was 2.7%. The results of the present study indicate that percutaneous RFA was an effective treatment for small RCCs with respect to management of cancer, minimal invasiveness and minimal loss of renal function, particularly in patients for whom surgery would be a high risk and those at increased risk of deterioration of renal function.

Randomized, Noncomparative, Phase II Trial of Early Switch From Docetaxel to Cabazitaxel or Vice Versa, With Integrated Biomarker Analysis, in Men With Chemotherapy-Naïve, Metastatic, Castration-Resistant Prostate Cancer.

Purpose The TAXYNERGY trial ( ClinicalTrials.gov identifier: NCT01718353) evaluated clinical benefit from early taxane switch and circulating tumor cell (CTC) biomarkers to interrogate mechanisms of sensitivity or resistance to taxanes in men with chemotherapy-naïve, metastatic, castration-resistant prostate cancer. Patients and Methods Patients were randomly assigned 2:1 to docetaxel or cabazitaxel. Men who did not achieve ≥ 30% prostate-specific antigen (PSA) decline by cycle 4 (C4) switched taxane. The primary clinical endpoint was confirmed ≥ 50% PSA decline versus historical control (TAX327). The primary biomarker endpoint was analysis of post-treatment CTCs to confirm the hypothesis that clinical response was associated with taxane drug-target engagement, evidenced by decreased percent androgen receptor nuclear localization (%ARNL) and increased microtubule bundling. Results Sixty-three patients were randomly assigned to docetaxel (n = 41) or cabazitaxel (n = 22); 44.4% received prior potent androgen receptor-targeted therapy. Overall, 35 patients (55.6%) had confirmed ≥ 50% PSA responses, exceeding the historical control rate of 45.4% (TAX327). Of 61 treated patients, 33 (54.1%) had ≥ 30% PSA declines by C4 and did not switch taxane, 15 patients (24.6%) who did not achieve ≥ 30% PSA declines by C4 switched taxane, and 13 patients (21.3%) discontinued therapy before or at C4. Of patients switching taxane, 46.7% subsequently achieved ≥ 50% PSA decrease. In 26 CTC-evaluable patients, taxane-induced decrease in %ARNL (cycle 1 day 1 v cycle 1 day 8) was associated with a higher rate of ≥ 50% PSA decrease at C4 ( P = .009). Median composite progression-free survival was 9.1 months (95% CI, 4.9 to 11.7 months); median overall survival was not reached at 14 months. Common grade 3 or 4 adverse events included fatigue (13.1%) and febrile neutropenia (11.5%). Conclusion The early taxane switch strategy was associated with improved PSA response rates versus TAX327. Taxane-induced shifts in %ARNL may serve as an early biomarker of clinical benefit in patients treated with taxanes.

[CLINICAL ANALYSIS ABOUT PERCUTANEOUS NEEDLE BIOPSY FOR RENAL MASSES].

(Objective) We investigated the efficacy and safety of percutaneous renal mass biopsy retrospectively. (Methods) A retrospective review was performed of 44 patients (46 renal masses) who received ultrasound and/or computed tomography guided percutaneous biopsy of a solid renal mass between April 2004 and December 2012 in National Defense Medical College Hospital. (Results) The median renal mass size was 45 (range 15-140) mm with a median of 2 (1-5) cores taken. Thirteen masses were biopsied for differential diagnosis between RCC and other malignancies (or benign renal tumors), 11 were biopsied for differential diagnosis between RCC and renal pelvic urothelial carcinoma, 10 unresectable masses were biopsied to confirm the diagnosis pathologically before starting medication, and 12 small masses were biopsied before radio-frequency ablation. Of the initial 46 biopsies, 38 (82.6%) were diagnostic. The median lesion sizes in the diagnostic and nondiagnostic biopsy specimens were 45 (15-140) mm and 43 (17-128) mm. The median numbers of diagnostic and nondiagnostic cores were 2 (1-5) and 1.5 (1-4). These size and core number differences between the diagnostic and nondiagnostic biopsy specimens are not statistically significant. Of initial nondiagnostic 8 masses, 3 masses that were performed repeat biopsy resulted in determined diagnosis finally. There were mild postprocedural hematomas not requiring blood transfusion. There was no tumor dissemination after renal mass biopsy. (Conclusions) Percutaneous biopsy of renal masses is a safe procedure that provides diagnostic information.

[A CASE OF METASTATIC BLADDER UROTHELIAL CARCINOMA WHOSE DISEASE WAS CONTROLLED FOR A RELATIVE LONG PERIOD BY MULTIDISCIPLINARY TREATMENT INCLUDING RADIATION TO A LUNG METASTASIS AND MULTIPLE COURSES OF CHEMOTHERAPY].

A 67-year-old woman complained of urinary frequency and gross hematuria. She was referred to our hospital with the diagnosis of bladder tumor. Transurethral resection of the bladder tumor (TURBT) was performed and pathological diagnosis was urothelial carcinoma (G2>G3) with muscular invasion. Because she hoped bladder preservation therapy, she received two courses of M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) therapy, one course of arterial infusion chemotherapy, and chemoradiotherapy with cisplatin. After those therapies she underwent 4 times of TURBT and two courses intravesical BCG therapy. However, solitary lung metastasis appeared 19 months after the initial TURBT. Multidisciplinary treatments including 25 courses of various multiagent chemotherapies, radiation therapy to the lung metastasis and surgical resection of a urethral recurrence were performed. Although a localized radiation pneumonitis was developed, the lung metastasis appeared to be controlled for 26 months after the radiation therapy to the lung. Bilateral ureteral and renal pelvic tumors appeared after the radiation therapy. Severe bleeding was occurred from renal pelvic tumors several times and she needed the hospital stay 2 times. Active bleeding stopped after the administration of chemotherapy each time. Although she died of occlusive jaundice due to the liver metastasis, she had been alive due to the multidisciplinary treatment for 67 months after lung metastasis appearance with relatively good performance status.

Preoperative serum docosahexaenoic acid level predicts prognosis of renal cell carcinoma.

The recent discovery and clinical development of targeted agents have expanded treatment options in metastatic renal cell carcinoma (RCC). However, metastatic RCC remains a lethal disease. Complete response is rare and treatment with targeted agents eventually fails in the majority of the patients. Therefore, there is a need for developing a prognostic tool and a novel therapeutic agent for RCC to improve the follow-up strategy after surgical treatment. Clinical data, including patient characteristics, serum fatty acid profile, clinicopathological parameters and clinical outcome, were obtained from 112 patients with RCC prior to surgical treatment. Preoperative fatty acid levels were grouped according to patient characteristics, such as performance status, body mass index or pathological parameters, and were analyzed using the Mann-Whitney U test. Cancer-specific survival in the high and low docosahexaenoic acid (DHA) level groups were compared using the Kaplan-Meier method. Cox proportional hazards models were applied to determine the independent prognostic factors associated with shortened cancer-specific survival. The serum DHA level in patients with metastasis was significantly lower compared with that in patients without metastasis (P=0.047). Low serum DHA level, presence of metastasis and cachexia were independent predictors of shortened cancer-specific survival in a multivariate Cox proportional hazard model (P=0.033, hazard ratio = 4.43). Patients with a serum DHA level below the median value exhibited significantly shorter cancer-specific survival compared with those with a higher serum DHA level (P=0.008). Thus, according to our results, the preoperative serum DHA level may be able to predict the surgical outcome of RCC. However, this finding requires validation by large-scale prospective studies.

Tumor necrosis is a strong predictor for recurrence in patients with pathological T1a renal cell carcinoma.

Patients with pT1aN0M0 renal cell carcinoma (RCC) generally have good prognosis, and recurrence is rare. However, metastasis develops postoperatively in a small number of patients with pT1aN0M0 RCC. The present study was undertaken to identify predictors for recurrence in patients with pT1aN0M0 RCC. We reviewed the clinicopathological factors of 133 patients with pT1aN0M0 RCC who underwent radical or partial nephrectomy at the Department of Urology, National Defense Medical College (Saitama, Japan). Clinicopathological factors, including age, gender, tumor size, histological subtype, tumor grade, microvascular invasion, histological tumor necrosis, C-reactive protein levels and performance status were reviewed. These factors were compared between patients with and without postoperative recurrence. Recurrence-free survival (RFS) and cause-specific survival (CSS) rates were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed to determine independent factors predicting recurrence in patients with pT1aN0M0 RCC. The 5-year RFS and CSS rates were 97.2 and 99.1%, respectively. When clinicopathological factors were compared between patients with and without recurrence, tumor size (P=0.0390) and percentage of tumor necrosis (P<0.0001) were significantly different between groups. All patients with recurrence had primary lesions ≥3 cm. By univariate analysis, tumor size (P=0.0379) and the presence of tumor necrosis (P=0.0319) were significant predictors for recurrence; tumor necrosis was also an independent predictor for recurrence (P=0.0143). In patients with pT1b tumors ≤5 cm (recurrence rate, 16.8%; n=48), the percentage of tumor necrosis was significantly higher in patients with recurrence compared with those without (P=0.0261). This suggests that tumor necrosis may be an important predictor for recurrence in small RCCs. Although recurrence is rare in pT1a RCC, the presence of tumor necrosis may be an important predictor for recurrence. Particularly, patients presenting with pT1a RCC with histological tumor necrosis should undergo careful follow-up.

Microtubule inhibitor-based antibody-drug conjugates for cancer therapy.

The specificity of monoclonal antibodies represents a potential therapeutic advantage, but their use as single agents in oncology has proven limited to date. The development of antibody-drug conjugates (ADCs) takes advantage of the specificity of the monoclonal antibody and potent cytotoxic effect of chemotherapy, leading to enhanced cytotoxicity in target cells and limiting toxicity to normal tissue. Microtubules represent a validated oncologic target in a range of tumor types, with a number of anti-microtubule targeting cytotoxic drugs approved for cancer use. The systemic use of potent microtubule-binding agents is limited by their effects in normal cells, which leads to toxicity including myelosuppression and peripheral neuropathy. Linking these agents to monoclonal antibodies may limit toxicity to normal tissues and increase drug concentration in target tissues, also allowing the use of more potent agents which would be too toxic to administer in their unbound form. Two such ADCs have been approved for clinical use and many others are in development. Here we review the characteristics of each of the ADC components that have led to efficacious therapies and discuss some of the tubulin inhibitor-based ADCs in development for cancer therapy.

Preoperative risk factors for extraurothelial recurrence in patients with ureteral cancer treated with radical nephroureterectomy.

PURPOSE: Recent studies have suggested that lymph node dissection may improve the prognosis in patients with upper tract urothelial carcinoma. Therefore, patients who will benefit from lymph node dissection need to be selected before surgery. Because patients who have extraurothelial recurrence theoretically include those whose prognoses are improved by lymph node dissection, we conducted this study to determine the preoperative predictors of extraurothelial recurrence in patients with ureteral cancer. MATERIALS AND METHODS: Because it is not appropriate to categorize the preoperative radiologic findings of ureteral cancer and those of renal pelvic cancer using the same classification criteria, we focused on ureteral cancer. We reviewed preoperative factors in 70 patients with ureteral cancer treated with radical nephroureterectomy. Laboratory tests including inflammatory indices, tumor markers and estimated glomerular filtration rate, along with radiologic findings, were evaluated. Multivariate analyses were performed to determine independent factors predicting extraurothelial recurrence in patients with ureteral cancer. RESULTS: Positive cytology, cT stage 3 or greater, length of ureteral cancer 3 cm or greater and estimated glomerular filtration rate less than 60 ml/minute/1.73 m2 were independent predictors of extraurothelial recurrence on multivariate analysis. When patients were stratified into 3 groups according to the number of risk factors, the 3-year extraurothelial recurrence-free survival rates were 95.2% in the low risk group, 75.8% in the intermediate risk group and 25.1% in the high risk group. CONCLUSIONS: Positive cytology, cT stage 3 or greater, length of ureteral cancer 3 cm or greater and estimated glomerular filtration rate less than 60 ml/minute/1.73 m2 were preoperative predictive factors of extraurothelial recurrence in patients with ureteral cancer and lymph node dissection may be omitted for low risk patients.

[Causes and salvage of failed urethroplasties for traumatic urethral injury].

OBJECTIVES: Salvage urethroplasty after failed repair of traumatic urethral injury is a urological challenge, and we herein describe our experience with it. METHODS: From October 2010 to January 2012, five patients underwent salvage repair of failed urethroplasties for traumatic urethral injuries: three bulbar straddle injuries and two pelvic fracture urethral injuries. One of the three failed urethroplasties for bulbar straddle injuries was a stricture excision and primary anastomosis, and its failure was due to periurethral abscess formation. Another was an augmented anastomotic urethroplasty using buccal mucosa, and its failure was due to periurethral abscess formation. The third was a tube graft urethroplasty using buccal mucosa, and its failure was due to a stricture at the anastomotic site. Two failed urethroplasties for pelvic fracture urethral injuries were perineal anastomotic repairs combined with corporal separation and inferior pubectomy, and the failures of both were due to ischemic bulbar necrosis. The urethral gap lengths estimated from urethrograms ranged from 12 to 45 mm (mean = 26 mm). RESULTS: Urethroplasties in all patients with bulbar straddle injuries were salvaged by stricture excision and primary anastomosis with corporal separation, and urethroplasties in both patients with pelvic fracture urethral injuries were salvaged by abdominal transpubic perineal urethroplasty. Although the patients who underwent transpubic urethroplasty had transient pelvic girdle pain, no severe complications were observed. All patients were for 10 to 25 months postoperatively (mean = 16 months) able to void satisfactorily without additional treatment. CONCLUSIONS: Failed urethroplasties for traumatic urethral injuries can be salvaged with a second reconstruction surgery. The procedure of choice for this salvage is anastomotic urethroplasty with techniques for tension-free anastomosis.