The effect of antiplatelet therapy on outcomes in patients who underwent laparoscopic radical nephrectomy: A Japanese single-center study.

OBJECTIVES: The number of patients receiving antiplatelet therapy (APT) who have undergone laparoscopic radical nephrectomy is increasing. However, it is unclear whether APT affects the outcomes of patients undergoing radical nephrectomy. We investigated the perioperative outcomes of radical nephrectomy in patients with and without APT. METHODS: We retrospectively collected data from 89 Japanese patients who underwent laparoscopic radical nephrectomy for clinically diagnosed renal cell carcinoma (RCC) at Kokura Memorial Hospital between March 2013 and March 2022. We analyzed information related to APT. We divided the patients into two groups: the APT group (patients receiving APT) and the N-APT group (patients not receiving APT). Moreover, the APT group was further divided into the C-APT group (patients with continuous APT) and the I-APT group (patients with interrupted APT). We compared the surgical outcomes of these groups. RESULTS: Among 89 patients eligible for the study, 25 received APT and 10 continued APT. Even though the patients who received APT had a high American Society of Anesthesiologists physical status and many complications, including smoking, diabetes, hypertension, and chronic heart failure, no significant difference in the intra- or postoperative outcomes, including bleeding complications, was observed regardless of whether the patients received APT or continued APT. CONCLUSIONS: We concluded that in laparoscopic radical nephrectomy, continuation of APT is an acceptable strategy for patients with thromboembolic risk caused by interruption of APT.

Differential impact of proton pump inhibitor on survival outcomes of patients with advanced urothelial carcinoma treated with chemotherapy versus pembrolizumab.

OBJECTIVES: We clarified the effect of concomitant proton pump inhibitor use on oncological outcomes in patients with advanced urothelial carcinoma treated either with chemotherapy or immune checkpoint inhibitor. METHODS: We retrospectively reviewed patients with advanced urothelial carcinoma who received paclitaxel-gemcitabine therapy or pembrolizumab after platinum-based chemotherapy. The patients were divided into four groups based on the treatment regimen and the concomitant use of proton pump inhibitor. We compared survival outcomes between the groups and determined which factors predicted overall survival. RESULTS: Among the 60 and 75 patients treated with paclitaxel-gemcitabine and pembrolizumab, 15 and 29 used a concomitant proton pump inhibitor. Progression-free and overall survival was significantly shorter in patients who were administered pembrolizumab with concomitant proton pump inhibitor compared to those without. The use of a concomitant proton pump inhibitor had no effect on survival outcomes in patients who received paclitaxel-gemcitabine therapy. Furthermore, progression-free and overall survival were significantly shorter in patients treated with paclitaxel-gemcitabine therapy compared to those treated with pembrolizumab among patients without concomitant proton pump inhibitor. In contrast, there was no difference in survival outcomes between the two regimens among patients with concomitant proton pump inhibitor. Concomitant proton pump inhibitor use was associated with poor overall survival only in patients treated with pembrolizumab. CONCLUSION: The use of a concomitant proton pump inhibitor use had no impact on oncological outcomes in patients with advanced urothelial carcinoma treated with paclitaxel-gemcitabine therapy, different from those treated with pembrolizumab.

Association Between Body Mass Index and Outcomes in Patients With Urothelial Carcinoma Treated With Pembrolizumab.

BACKGROUND/AIM: We aimed to clarify the association between body mass index (BMI) and clinical outcomes of pembrolizumab treatment for advanced urothelial cancer (UC). PATIENTS AND METHODS: We retrospectively reviewed the records of patients with advanced UC who received pembrolizumab after chemotherapy between March 2018 and December 2021. Patients were divided according to BMI into the non-overweight group (BMI <25 kg/m2) and the overweight group (BMI ≥25 kg/m2). We compared the two groups' tumour response, survival rates, and incidence of immune-related adverse events (irAEs) and investigated the factors predicting survival. RESULTS: Of 84 eligible patients, 63 (75%) and 21 (25%) were in the non-overweight and overweight groups, respectively. Although the objective response rate was higher in the overweight group (55%) than that in the non-overweight group (29%), the difference was not significant. Progression-free survival (PFS) was significantly longer in the overweight group (median 15.2 months) than that in the non-overweight group (median 4.8 months; p=0.01). Overall survival was also longer in the overweight group (median 36.1 months) compared to that in the non-overweight group (13.4 months), but the difference was not significant (p=0.11). Multivariable analysis showed that overweight was significantly associated with favourable PFS. Any and severe (grade 3) irAEs were observed in 15 (24%) and 5 (7.9%) patients in the non-overweight group, respectively, and in 8 (38%) and 2 (9.5%) patients in the overweight group, respectively, but the differences were not significant. CONCLUSION: BMI was associated with oncological outcomes in patients with advanced UC who received pembrolizumab but not with the development of irAEs.

Severe hypoglycaemia under abemaciclib administration in a patient with breast cancer: A case report.

The current study reports the case of an 80-year-old woman who experienced severe hypoglycaemia after abemaciclib administration, with a recovery time of ~46 h. Abemaciclib is a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor that is used to treat metastatic breast cancer. A side effect of abemaciclib administration is an increase in creatinine levels. The half-life (t1 / 2) of 150 mg abemaciclib in patients with breast cancer was reported to be 17.5 h (nearly lower limit), and the time to reach Cmax was ~5 h (Tmax, 4-6 h). Therefore, the total time to reach half the maximum blood concentration after abemaciclib administration is ~24 h (Tmax + t1 / 2=5+17.5=22.5 h). As abemaciclib is administered twice daily, a considerable amount (Cmax = 123 ng/ml) may persist in the blood following the initial dose. Upon repeated administration, the blood abemaciclib concentration in patients with metastatic liver tumours might increase, although their liver function remains normal. The patient described in the current study had a creatinine level of 1.05 mg/dl at the start of abemaciclib administration. At the time of emergency hospitalisation (on day 5 of abemaciclib administration), the creatinine level was 1.40 mg/dl; however, dehydration was not observed. The patient had been administered the same dose of glimepiride for >1 year and had not experienced hypoglycaemia previously. It can be speculated that the increase in blood creatinine level had some effect on glimepiride metabolism. It is thought that administered abemaciclib enhances metabolic delay in the blood in the same way as in patients with impaired liver function, and as a result, the creatinine level increases in patients with liver metastases. This causes a decrease in renal function, which in turn results in an increase in blood concentration of glimepiride, consequently leading to severe hypoglycaemia. Therefore, clinicians must be careful when using abemaciclib in patients with liver metastases, diabetes and poor renal function.

Prognostic value of pre-treatment risk stratification and post-treatment neutrophil/lymphocyte ratio change for pembrolizumab in patients with advanced urothelial carcinoma.

BACKGROUND: Pembrolizumab is effective in a limited number of patients with advanced urothelial carcinoma (UC). Therefore, we evaluated the prognostic value of clinical biomarkers following pembrolizumab treatment in patients with advanced UC. METHODS: We retrospectively reviewed the medical records of 121 patients with platinum-refractory advanced UC who received pembrolizumab. Inflammation-based prognostic scores before and 6 weeks after the treatment were recorded. The categorical variables influencing overall survival (OS) and objective response rate (ORR) were analyzed. RESULTS: Multivariate analyses showed that pretreatment Eastern Cooperative Oncology Group (ECOG) performance score (PS), presence of only lymph node metastasis (only LN mets), C-reactive protein (CRP), and neutrophil/lymphocyte ratio (NLR) were independent prognostic factors for OS (P = 0.0077; RR = 2.42, P = 0.0049; RR = 0.36, P = 0.0047; RR = 2.53, and P = 0.0079; RR = 2.33, respectively). The pretreatment risk stratification using ECOG PS, only LN mets, CRP, and NLR was used for estimating the OS (P < 0.0001) and ORR (P < 0.0001). Furthermore, changes in NLR in response to pembrolizumab were significantly associated with the OS (P = 0.0002) and ORR (P = 0.0023). This change was also significantly correlated with OS even in the high-risk group stratified by this pretreatment risk stratification (P = 0.0069). CONCLUSIONS: This pretreatment risk stratification may be used for estimating the OS and ORR of patients with advanced UC treated with pembrolizumab. If changes in NLR in response to pembrolizumab treatment improve, pembrolizumab should be continued.

Tumor Location Based Segmentation in Upper-Tract Urothelial Carcinoma Impacts on the Urothelial Recurrence-Free Survival: A Multi-Institutional Database Study.

INTRODUCTION AND OBJECTIVES: The predictive impact of primary tumor location for patients with upper-tract urothelial carcinoma (UTUC) in the presence of concomitant urothelial bladder cancer, along with urothelial recurrence after the curative treatment is still contentious. We evaluated the association between precise tumor location and concomitant presence of urothelial bladder cancer and urothelial recurrence-free survival in patients with UTUC treated by radical nephroureterectomy with a bladder cuff. METHODS: A total of 1,349 patients with localized UTUC (Ta-4N0M0) from a retrospective multi-institutional cohort were studied. We queried four UTUC databases. This retrospective clinical series was of patients with localized UTUC managed by nephroureter-ectomy with a bladder cuff, for whom data were from the Nishinihon Uro-Oncology Collaborative Group registries. Patients with a history of chemotherapy or radiotherapy were excluded from the study. Associations between the location of the tumor and subsequent outcome following nephroureterectomy were assessed using COX multivariate analysis. The location of the tumor was verified by pathological samples. Urothelial recurrence was defined as tumor relapse in any local urothelium, and coded apart from distant metastasis. The median follow-up was 34 months. RESULTS: A total of 887 patients had an evaluation of the tumor location in which 475 patients had pelvic tumors (53.6%), 96 had ureteral tumors in the U1 segment (10.8%), 87 in the U2 segment (9.8%), and 176 in the U3 segment (19.8%). There were 52 patients who had multifocal tumors (5.9%) as follows: 8 (0.9%) in the pelvis and ureter, 11 (1.2%) in U1 + U2, 1 (0.1%) in U1 + U3, 27 (3.0 %) in U2 + U3, and 6 (0.7%) in U1 + U2 + U3. In all, 145 (16.3%) had concomitant bladder tumors. Logistic regression analysis of gender, age, hydronephrosis, cytology, performance status, grade, lymphovascular invasion, pT, pN, and tumor focality showed that tumor location was associated with the presence of concomitant bladder cancer (p = 0.004, HR = 1.265). When the tumor location was stratified into 8 segments, including multifocal tumors, only the U3 segment remained as a predictor for the presence of concomitant bladder cancer (p = 0.002, HR = 2.872). Kaplan-Meier analysis for unifocal disease showed that lower ureter tumors (a combination of U2 and U3) had a worse prognosis for urothelial recurrence than pelvic tumors or upper ureteral tumors (U1) (p < 0.001 for lower ureteral tumors versus pelvic tumors, p = 0.322 for upper ureteral tumor versus pelvic tumor by log rank). Multivariate analysis showed that lower ureter remained as a prognostic factor for urothelial recurrence after adjusting for gender, age, hydronephrosis, urine cytology, lymphovascular invasion, pT, and pN (p < 0.001, HR = 1.469), and a similar tendency was found when the analysis was run for patients without concomitant bladder tumors (p = 0.003, HR = 1.446). Patients with lower ureteral tumors had a higher prevalence of deaths (HR = 2.227) compared to patients with upper ureter tumors. CONCLUSIONS: This multi-institutional study showed that the primary tumor locations were independently associated with the presence of concomitant bladder tumors and subsequent urothelial recurrence.

Prognostic value of risk stratification using blood parameters for nivolumab in Japanese patients with metastatic renal-cell carcinoma.

BACKGROUND: Nivolumab is a standard treatment for previously treated advanced renal-cell carcinoma. However, nivolumab is effective in only a limited number of patients; therefore, we evaluated the prognostic value of several biomarkers, including inflammation-based prognostic scores and changes in these scores following nivolumab treatment in Japanese patients with metastatic renal-cell carcinoma. METHODS: We retrospectively reviewed the medical records of 65 patients with previously treated metastatic renal-cell carcinoma and who received nivolumab. Inflammation-based prognostic scores, including neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, lymphocyte/monocyte ratio, and Glasgow prognostic score before and 6 weeks after the treatment were recorded. Categorical variables influencing disease-specific survival were compared using Cox proportional-hazards regression models. RESULTS: Univariate analysis showed that Memorial Sloan-Kettering Cancer Center risk score (P = 0.0052), lactate dehydrogenase (P = 0.0266), lymphocyte/monocyte ratio (P = 0.0113), and platelet/lymphocyte ratio (P = 0.0017) had a significant effect on disease-specific survival. Multivariate analyses showed that platelet/lymphocyte ratio and lactate dehydrogenase were found to be independent prognostic factors for disease-specific survival (P = 0.0008, risk ratio (RR) = 7.95, 95% confidence interval, 2.16-51.64 and P = 0.0123, RR = 3.92, 95% confidence interval, 1.37-10.80, respectively). The combination of platelet/lymphocyte ratio and lactate dehydrogenase was the most significant prognostic biomarker in metastatic renal-cell carcinoma (P < 0.0001). Changes in lymphocyte/monocyte ratio and platelet/lymphocyte ratio in response to nivolumab were significant prognostic factors for disease-specific survival (P < 0.0001 and P = 0.0477, respectively). CONCLUSIONS: The combination of platelet/lymphocyte ratio and lactate dehydrogenase may be a potential biomarker for estimating disease-specific survival in Japanese patients with metastatic renal-cell carcinoma treated by nivolumab.

Risk stratification by means of biological age-related factors better predicts cancer-specific survival than chronological age in patients with upper tract urothelial carcinoma: a multi-institutional database study.

BACKGROUND: Chronological age is an important factor in determining the treatment options and clinical response of patients with upper tract urothelial carcinoma (UTUC). Much evidence suggests that chronological age alone is an inadequate indicator to predict the clinical response to radical nephroureterectomy (RNU). PATIENTS AND METHODS: We retrospectively reviewed the data from 1510 patients with UTUC (Ta-4) treated by surgery. White blood cell (WBC) count, neutrophil-to-lymphocyte ratio, hemoglobin (Hb), platelets, albumin, alkaline phosphatase, lactate dehydrogenase, creatinine, and corrected calcium were tested by the Spearman correlation to indicate the direction of association with chronological age, which yielded significant, negative associations of Hb (p < 0.001) and WBC (p = 0.010) with chronological age. For scoring, we assigned points for these categories as follows; point '0' for Hb >14 (reference) and 13-13.9 [odds ratio (OR): 1.533], point '1' for 12-12.9 (OR: 2.391), point '2' for 11-11.9 (OR: 3.015), and point '3' for <11 (OR: 3.584). For WBC, point '1' was assigned for >9200 (OR: 2.541) and '0' was assigned for the rest; 9200-8500 (reference), 8499-6000 (OR: 0.873), 5999-4500 (OR: 0.772), 4499-3200 (OR: 0.486), and <3200 (OR: 1.277). RESULTS: The 10-year cancer-specific survival (CSS) in the higher risk group with scores of 4 or higher in patients age <60 years was worse than a score of 0, or 1 in age >80 years [mean estimated survival 69.7 months, confidence interval (CI): 33.3-106 versus 103.5. CI: 91-115.9]. The concordance index between biological age scoring and chronological age was 0.704 for CSS and 0.798 for recurrence-free survival. The limitation of the present study is the retrospective nature of the cohort included. CONCLUSIONS: The biological age scoring developed for patients with UTUC undergoing RNU. It was applicable to those with localized disease and performed well in diverse age populations.

Identification of curable high-risk prostate cancer using radical prostatectomy alone: who are the good candidates for undergoing radical prostatectomy among patients with high-risk prostate cancer?

BACKGROUND: Currently, there is no consensus regarding which patients with high-risk prostate cancer (PCa) would benefit the most by radical prostatectomy (RP). We aimed to identify patients with high-risk PCa who are treatable by RP alone. METHODS: We retrospectively reviewed data on 315 patients with D'Amico high-risk PCa who were treated using RP without neoadjuvant or adjuvant therapy at the institutions of the Yamaguchi Uro-Oncology Group between 2009 and 2013. The primary endpoint was biochemical progression-free survival (bPFS) after RP. Risk factors for biochemical progression were extracted using the Cox proportional hazard model. We stratified the patients with high-risk PCa into 3 subgroups based on bPFS after RP using the risk factors. RESULTS: At a median follow-up of 49.9 months, biochemical progression was observed in 20.5% of the patients. The 2- and 5-year bPFS after RP were 89.4 and 70.0%, respectively. On multivariate analysis, Gleason score (GS) at biopsy (≥ 8, HR 1.92, p < 0.05) and % positive core (≥ 30%, HR 2.85, p < 0.005) were independent predictors of biochemical progression. Patients were stratified into favorable- (0 risk factor; 117 patients), intermediate- (1 risk factor; 127 patients), and poor- (2 risk factors; 57 patients) risk groups, based on the number of predictive factors. On the Cox proportional hazard model, this risk classification model could significantly predict biochemical progression after RP (favorable-risk, HR 1.0; intermediate-risk, HR 2.26; high-risk, HR 5.03; p < 0.0001). CONCLUSION: The risk of biochemical progression of high-risk PCa after RP could be stratified by GS at biopsy (≥ 8) and % positive core (≥ 30%).

Biological Behavior and Long-Term Outcomes of Carcinoma In Situ in Upper Urinary Tract Managed by Radical Nephroureterectomy.

PURPOSE: In patients with urothelial carcinoma CIS (carcinoma in situ) generally has a poor prognosis. However, to our knowledge the outcomes of pure/primary CIS and the behavior of CIS concomitant with pTa-pT4 upper tract urothelial carcinoma managed by nephroureterectomy have not been previously specified. We explored the biological and prognostic features of concomitant CIS compared with those of pure/primary CIS. MATERIALS AND METHODS: We queried a multicenter upper tract urothelial carcinoma database. Data from NUOG (Nishinihon Uro-Oncology Group) were analyzed, including patient gender, age, presence of bladder cancer and pT stage. Clinicopathological features were compared between the different subtypes. Cancer specific and overall survival, and the relative excess risk of death were estimated by CIS subtype. RESULTS: We identified 163 patients with CIS in the upper urinary tract, of whom pure/primary CIS was noted in 24.5%. In the concomitant CIS cohort the pathological diagnosis of the nonCIS region was pTa, pT1, pT2, pT3 and pT4 in 4.9%, 22.8%, 25.2%, 44.7% and 1.6% of patients, respectively. The sensitivity of a selective urine cytology test was higher in the pure/primary CIS group than in the concomitant CIS group (60.0% vs 37.4%). At a median followup of 32 months 10-year estimated mean cancer specific survival was 92.4 months (range 83.7 to 101.0) in the overall CIS cohort. Ten-year estimated mean cancer specific survival in patients with pure/primary CIS was significantly longer than in patients with concomitant carcinoma in situ (111.8 months, range 101.0 to 122.6 vs 85.89, range 75.3 to 96.5, log rank p = 0.007). CONCLUSIONS: Patients presenting with concomitant CIS have a worse outcome than those who present with pure/primary CIS, suggesting a need to differentiate these 2 entities in the treatment decision process.

The systemic inflammation-based Glasgow Prognostic Score as a powerful prognostic factor in patients with upper tract urothelial carcinoma.

INTRODUCTION AND OBJECTIVE: The combination of C-reactive protein and albumin, the Glasgow Prognostic Score (GPS), had independent prognostic value in patients with varying cancers, except for upper tract urothelial carcinoma (UTUC). The aim of this study was to describe the relationship between GPS and survival in patients with UTUC after adjustment for other prognostic factors. MATERIALS AND METHODS: We queried 2 UTUC databases. Retrospective clinical series on patients with localized UTUC managed by nephroureterectomy with bladder cuff, for whom data from the Yamaguchi Uro-Oncology Group and Osaka Medical College registry, including age, presence of bladder cancer, pT stage, lymphovascular invasion, C-reactive protein (CRP) and albumin, were analyzed. The GPS was constructed by combining CRP and albumin. Cancer specific survival (CSS) and overall survival (OS) and relative excess risk of death were estimated by GPS categories after adjusting for gender, age, ECOG performance status (PS), grade, and lymphovascular invasion (LVI). RESULTS: Seven hundred and twenty four UTUC patients were identified. Our final cohort included 574 patients; of these, 29.2% died during a maximum follow up of 16.7 years. The estimated mean 10-year CSS of patients with GPS of scre-0, -1, and -2 was 99.5, 95.1, and 75.9 months, respectively. Patients with GPS of score-2 had poorest 10-year estimated mean OS of 67.6 months (57.2-77.9). Raised GPS also had a significant association with excess risk of cancer death at 10 years (GPS 2: Relative Excess Risk = 1.74, 95% CI 1.20-2.54) after adjusting for gender, patients' age, ECOG PS, and tumor focality. C-index of GPS both for CSS and OS were superior to patients' age and tumor focality, and comparable to grade. CONCLUSIONS: The GPS is an independent prognostic factor for CSS and OS after surgery with curative intent for localized UTUC. It significantly increases the accuracy of established prognostic factors. The GPS may provide a meaningful adjunct for patient counseling and clinical trial design.

Changes in oncological outcomes after radical nephroureterectomy in patients with upper urinary tract urothelial carcinoma treated in the last two decades: a retrospective analysis based on a multicenter collaborative study.

OBJECTIVE: We investigated chronological changes in the outcomes of patients with upper urinary tract urothelial carcinoma treated in the past two decades, during which there was an important change in treatment paradigm. METHODS: A retrospective review was conducted of 1180 urinary tract urothelial carcinoma patients who underwent radical nephroureterectomy in multicenter collaborative institutions between 1996 and 2015. The patients were divided into four groups according to the year when radical nephroureterectomy was performed, as follows: 1996-2000 (period 1; P1), 2001-05 (P2), 2006-10 (P3) and 2011-15 (P4). Variables including tumor grade, T and N categories, administration of perioperative chemotherapy and treatment outcomes were compared among the four groups. RESULTS: There were 146 (12%), 312 (27%), 459 (39%) and 263 (22%) patients in the P1, P2, P3 and P4 groups, respectively. The proportion of patients harboring pT2/3 and Grade 3 tumors increased gradually from 42% (P1) to 58% (P4) and from 49% (P1) to 65% (P4), respectively. The 5-year disease-free survival rates were 74%, 74%, 73% and 75%, and the 5-year overall survival rates were 74%, 65%, 67% and 72% for the P1, P2, P3, and P4 groups, respectively. Multivariate analysis with adjustment for possible confounding factors revealed no significant differences in disease-specific survival, overall survival or intravesical recurrence-free survival among the four groups. CONCLUSIONS: Despite advances in diagnostic instruments, surgery and systemic chemotherapy, the clinical outcome of urinary tract urothelial carcinoma after radical surgery has not significantly improved over the last two decades, and further research is therefore required.

BUBR1 overexpression predicts disease-specific survival after nephroureterectomy in patients with upper tract urothelial carcinoma.

OBJECTIVE: To date, there are few reliable markers to distinguish tumors with aggressive characteristics in upper tract urothelial carcinoma. The purpose of this study was to identify a biomarker related to genetic instability (chromosomal instability or microsatellite instability) with prognostic value, in patients with upper tract urothelial carcinoma. METHODS: Expression of chromosomal instability-related markers (BUBR1, p53, polo-like kinase 1) and microsatellite instability-related markers (mismatch repair proteins, MLH1 and MSH2) were assessed by immunohistochemistry in 100 patients who had radical nephroureterectomy for upper tract urothelial carcinoma. Numerical aberrations of chromosomes 7, 9 and 17 were evaluated by fluorescence in situ hybridization, which allowed an estimation of the degree of chromosomal instability. BUB1B copy number was examined by array-based comparative genomic hybridization in 32 patients with upper tract urothelial carcinoma. RESULTS: BUBR1 status was most significantly correlated with chromosomal instability-related and low mismatch repair parameters, according to the molecular biomarkers examined. Overexpression of BUBR1 is frequently detected in tumors with higher histological grade (P < 0.0001) and is significantly associated with chromosomal instability (P = 0.0071). Array-based comparative genomic hybridization revealed that no tumors (0%) showed BUB1B amplification and gain, indicating that overexpression of BUBR1 was independent of BUB1B copy number. For disease-specific survival, BUBR1 overexpression, lymphovascular invasion, pathological tumor stage, pathological lymph node involvement and low MSH2 expression were significant prognostic factors in univariate analyses. In multivariate analyses, BUBR1 overexpression was an independent prognostic factor for disease-specific survival (P = 0.0483, risk ratio 3.76, 95% confidence interval: 1.01-18.43). CONCLUSIONS: BUBR1 may have significant potential as a biomarker for estimating disease-specific survival in patients with upper tract urothelial carcinoma treated by radical nephroureterectomy.

Positive voided urine cytology predicts worse pathological findings of nephroureterectomy specimens in patients with upper tract urothelial carcinoma: does selective ureteral cytology have an additional efficacy?

OBJECTIVE: After radical nephroureterectomy, substantial numbers of patients with upper tract urothelial carcinoma are ineligible for adjuvant chemotherapy owing to diminished renal function. Accurate pre-operative prediction of worse pathological findings in radical nephroureterectomy specimens can guide appropriate patient selection for neoadjuvant chemotherapy. Herein, we evaluated pre-operative voided urine cytology and the additional efficacy of selective ureteral cytology for predicting pathological features in upper tract urothelial carcinoma patients. METHODS: This retrospective cohort study comprised 722 patients with upper tract urothelial carcinoma who underwent radical nephroureterectomy. Patients with concomitant bladder cancer and those who received neoadjuvant therapy were excluded. Finally, 437 patients with urinary cytology data were enrolled in the study. We assessed the positive voided urine and selective ureteral cytology for predicting higher pathological T stage (≥ pT3), higher tumor grade (3) and positive lymphovascular invasion. RESULTS: Previous bladder cancer, tumor location, clinical T stage and voided urine cytology (P = 0.029) were independently associated with ≥ pT3, whereas selective ureteral cytology was not. Gender, clinical N category and voided urine cytology (P = 0.017) were independently associated with tumor Grade 3, whereas selective ureteral cytology was not. Hydronephrosis, clinical T stage, clinical N category and voided urine cytology (P = 0.0021) were independently associated with lymphovascular invasion, whereas selective ureteral cytology was not. CONCLUSIONS: Pre-operative positive voided urine cytology was an independent predictor for worse pathological findings in radical nephroureterectomy specimens, while selective ureteral cytology had no additional efficacy. However, further studies with larger numbers of patients and complete data sets are needed to select patients for more aggressive treatments including neoadjuvant chemotherapy.

Running suture versus interrupted suture for vesicourethral anastomosis in retropubic radical prostatectomy: a randomized study.

OBJECTIVES: To determine the feasibility of vesicourethral anastomosis using running suture during retropubic radical prostatectomy and to compare the surgical outcomes of vesicourethral anastomosis using running suture with those of the standard interrupted suture technique. METHODS: A total of 60 patients undergoing radical prostatectomy from 2010 to 2012 at the Yamaguchi University Hospital, Japan were included in the present study, and were randomly assigned to vesicourethral anastomosis using running suture (n = 30 patients) or a standard interrupted suture technique group (n = 30 patients). Vesicourethral anastomosis using running suture was carried out with 12-bite sutures using 3-0 poliglecaprone. The primary end-point was the time to catheter removal. Patients' health-related quality of life was assessed using the Expanded Prostate Cancer Index Composite in 56 patients (28 patients in each group). RESULTS: No significant difference was found in the median suturing time between the two study groups (both 19 min, P = 0.449). The time to catheter removal was significantly better in the vesicourethral anastomosis using running suture group (hazard ratio 5.23, 95% confidence interval 1.73-17.65, P = 0.003). The pad-free rate was significantly higher in the vesicourethral anastomosis using running suture group at 1 month after surgery (20.7% vs 3.3%, P = 0.0463); however, there was no significant difference at 3 months and beyond. The Expanded Prostate Cancer Index Composite urinary and bowel summary scores at 1 month were significantly better in the vesicourethral anastomosis using running suture patients (both P < 0.01), though no significant difference was observed thereafter. A vesicourethral anastomosis stricture was noted in three patients (10%) in the standard interrupted suture technique group, and none in the vesicourethral anastomosis using running suture group. CONCLUSION: Running suture for vesicourethral anastomosis is feasible during retropubic radical prostatectomy. Furthermore, it offers better outcomes than the conventional standard interrupted suture technique, with a higher likelihood of improvement in patients' health-related quality of life.

Impact of variant histology on disease aggressiveness and outcome after nephroureterectomy in Japanese patients with upper tract urothelial carcinoma.

BACKGROUND: Patients with urinary bladder urothelial carcinoma (UC) with variant histology have features of more advanced disease and a likelihood of poorer survival than those with pure UC. We investigated the impact of variant histology on disease aggressiveness and clinical outcome after radical nephroureterectomy (RNU) in Japanese patients with upper tract UC (UTUC). Information on variant histology might guide appropriate patient selection for adjuvant therapy after RNU. METHODS: We enrolled 502 UTUC patients treated with RNU in this retrospective cohort study, and analyzed associations of variant histology with clinicopathological variables and disease-specific survival. RESULTS: The median follow-up was 41.4 months. A total of 60 (12.0 %) UTUC patients had variant histology. UTUC with variant histology was significantly associated with advanced pathological T stage (pT ≥ 3), higher tumor grade (G3), and more lymphovascular invasion (P < 0.0001). Variant histology in all patients was significantly associated with worse disease-specific survival after RNU on univariate analysis (P = 0.0004), but this effect did not remain significant on multivariate analysis. However, variant histology was a significantly independent predictor for disease-specific survival in patients with pT ≥ 3 tumors (P = 0.0095). CONCLUSIONS: UTUC with variant histology might be a phenotype of high-grade, locally aggressive advanced tumors rather than of systemic disease. Variant histology may be useful for selection of patients with pT ≥ 3 UTUC for adjuvant therapy. Prospective studies in a larger number of patients with a centralized pathological review are needed to confirm our results.

Copy number aberrations using multicolour fluorescence in situ hybridization (FISH) for prognostication in non-muscle-invasive bladder cancer (NIMBC).

OBJECTIVE: To investigate if detection of copy number aberrations of chromosomes 3, 7, 9p21, and 17 using multicolour fluorescence in situ hybridization (FISH) predicts patient outcome in non-muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS: In all, 118 bladder wash samples were prospectively collected from patients who underwent transurethral resection of bladder tumour (median age 50.5 years, male/female: 91/27, tumour grade 1/2/3: 18/52/42, stage pTis/Ta/T1: 8/62/42) from 2007 to 2010. The 118 samples were analysed using the UroVysion® kit to detect the copy numbers of chromosomes 3, 7, 9p21, and 17. The variant fraction (VF; the sum of the non-modal copy number fraction of each chromosome) was defined as abnormal when the percentage was ≥16%. The percentage deletion of 9p21 (fraction of null or one copy number of the 9p21 locus) was defined as abnormal when the percentage was ≥12%. Maffezzini risk criteria were also analysed in our cohorts. RESULTS: There was recurrence in 57 (48.3%) patients and disease progression in 12 (10.1%), with a median follow-up of 35.7 months. Multivariate analysis showed that the percentage 9p21 loss (>12%) was an independent prognostic factor for recurrence (P < 0.001, odds ratio [OR] 3.24, 95% confidence interval [CI] 1.85-5.62). For disease progression, tumour grade, positive urine cytology, concurrent carcinoma in situ, and a mean VF of >16% were significant prognostic factors in univariate analysis. In multivariate analysis, a mean VF of >16% was a prognostic factor for disease progression (P = 0.048, OR 6.07, 95% CI 1.02-57.45). CONCLUSIONS: Multicolour-FISH analysis using a commercially available kit could be a powerful tool not only for diagnosis, but also for prognostication in patients with NMIBC.

Risk group stratification based on preoperative factors to predict survival after nephroureterectomy in patients with upper urinary tract urothelial carcinoma.

BACKGROUND: After radical nephroureterectomy (RNU), substantial numbers of patients with upper urinary tract urothelial carcinoma (UUT-UC) are ineligible for adjuvant chemotherapy owing to diminished renal function. Accurate preoperative prediction of survival is considered important because neoadjuvant chemotherapy may be as effective for high-risk UUT-UC as for muscle-invasive bladder cancer. We performed risk group stratification to predict survival based on specific preoperative factors. METHODS: We enrolled 536 UUT-UC patients treated with RNU in this retrospective cohort study and assessed preoperative clinical and laboratory variables influencing disease-specific survival. RESULTS: The median follow-up was 40.9 months. Using univariate analysis, tumor location; number of tumors; hydronephrosis; clinical T stage; clinical N category; voided urine cytology; neoadjuvant chemotherapy; hemoglobin; white blood cell (WBC) counts; and C-reactive protein had a significant influence on disease-specific survival (P < 0.05). Multivariate analysis revealed that clinical T stage, voided urine cytology, and WBC were independent predictors (P = 0.041, P = 0.020, and P = 0.017, respectively). We divided patients into three risk groups based on the number of the three independent predictors: 0, low risk; 1, intermediate risk; 2 and 3, high risk. Significant differences in disease-specific survival were found among these risk groups (P ≤ 0.0047). CONCLUSIONS: Our results suggest that risk group stratification based on preoperative clinical T stage, voided urine cytology, and WBC counts may be useful for selection of UUT-UC patients for neoadjuvant chemotherapy. Prospective studies with larger numbers of patients and a longer follow-up period are needed to confirm our results.

Centrosome amplification in bladder washing cytology specimens is a useful prognostic biomarker for non-muscle invasive bladder cancer.

We investigated whether centrosome amplification (CA) obtained from bladder washing cytology (BWC) specimens may be a useful prognostic biomarker for patients with non-muscle invasive bladder cancer (NMIBC). The study cohort included 78 patients with pathologically confirmed NMIBC. BWC specimens were obtained from all patients during transurethral resection of bladder tumor (TURBT), and CA was evaluated by immunofluorescence staining using a pericentrin polyclonal antibody. A positive case of CA was defined as a specimen in which >5% of cells contained ≥3 centrosomes per cell. CA was detected in 26.9% (21 of 78) of BWC specimens obtained from NMIBC patients. Disease progression was observed in 11.5% (9 of 78) of patients, with a median follow-up of 32 months. In univariate analyses, CA obtained from BWC specimens, initial or recurrent, and washing cytology were significantly associated with progression-free survival (P = 0.009, 0.02, and 0.03, respectively). Multivariate Cox model analyses revealed that CA was the most significant prognostic factor for disease progression (hazard ratio: 2.22, 95% confidence interval: 1.13-4.90, P = 0.022). These data suggest that analysis of CA using bladder washing cytological specimens may provide crucial predictive information regarding disease progression in NMIBC.