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Objective The standard treatment for chronic myeloid leukemia (CML) is the continuous use of tyrosine kinase inhibitors (TKIs), which results in a favorable prognosis for the majority of patients. Recent studies have identified cardiovascular diseases (CVDs) as late adverse events (AEs) related to TKIs. In this study, we evaluated the long-term efficacy and AEs of TKIs, focusing on CVDs. Methods We performed a retrospective survey of CML patients (diagnosed from 2001 to 2016) treated with TKIs in Nagasaki Prefecture. Clinical data were obtained from their medical records. We analyzed the survival, estimated cumulative incidence of CVDs, and risk factors for CVD among CML patients treated with TKIs. Results The overall survival rate of 264 CML patients treated with TKIs (median age 58 years old) was 89.6% [95% confidence interval (CI), 84.9-92.9%], and 80.5% (95% CI, 73.4-85.9%) at 5 and 10 years after the CML diagnosis, respectively. CVD events occurred in 26 patients (9.8%, median age 67.5 years old) with a median 65.5 months of TKI treatment. The cumulative incidences at 2 and 5 years was 2.4% (95% CI, 1.0-4.8%) and 5.2% (95% CI, 2.8-8.6%), respectively. Hypertension and a high SCORE chart risk at the diagnosis of CML were associated with CVD events during TKI treatment. Conclusion TKI treatment contributed to the long-term survival of CML patients in Nagasaki Prefecture in a “real-world” setting, but the incidence of CVDs seemed to be increased in these patients. A proper approach to managing risk factors for CVD is warranted to reduce CVD events during TKI treatment.

Objective Classic Hodgkin lymphoma (CHL) has been regarded as a curable disease when treated appropriately, especially in younger patients, and ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) has been regarded as the standard regimen. However, a relatively poor prognosis has been reported in older patients with CHL, and the efficacy and tolerability of the ABVD regimen has not been fully elucidated. We retrospectively investigated the outcomes in patients with CHL treated with ABVD at our institute. Methods Twenty-five patients were evaluated; 14 were ≤60 years of age, and 11 were >60 years of age (older group). Results The ABVD doses were reduced in all patients in the older group; the median average relative dose intensity was 0.58. In the older group, the 5-year overall survival (OS) and median OS were 100% and not reached, respectively, for patients with early-stage CHL and 66.7% and not reached, respectively, for those with advanced-stage CHL. No patients died of CHL, and only one treatment-related death was observed in the older group. Conclusion ABVD with dose attenuation may represent a feasible and effective strategy for the treatment of older patients with CHL in clinical practice, particularly in those with early-stage disease, although the optimal degree of attenuation remains unclear.

The development process of recurrence in prostate cancer patients with pathologically organ-confined (pT2) disease and negative surgical margins is unclear. The aim of the present study was to determine factors associated with the development of biochemical recurrence following robot-assisted radical prostatectomy among those prostate cancer patients. We retrospectively reviewed the data of patients who underwent robot-assisted radical prostatectomy without neoadjuvant endocrine therapy. We evaluated prognostic factors in 1096 prostate cancer patients with pT2 disease and negative surgical margins. Univariate and multivariate Cox proportional hazards regression analyses were used to identify independent predictors for biochemical recurrence. Of the 1096 patients, 55 experienced biochemical recurrence during the follow-up period. The 5-year biochemical recurrence-free survival rate for patients with pT2 and negative surgical margins was 91.8%. On univariate analysis, clinical stage, biopsy Gleason score, percent of positive core, pathological Gleason score, and the presence of micro-lymphatic invasion were significantly associated with biochemical recurrence. On a multivariate analysis, the presence of micro-lymphatic invasion and a pathological Gleason score ≥ 4 + 3 were significant prognostic factors for biochemical recurrence. Based on these factors, we developed a risk stratification model. The biochemical recurrence-free survival rate differed significantly among the risk groups. The prognosis of prostate cancer patients with pT2 disease and negative surgical margins is favorable. However, patients with the presence of micro-lymphatic invasion and a pathological Gleason score ≥ 4 + 3 tend to experience biochemical recurrence more often after surgery. Therefore, careful follow-up might be necessary for those patients.

For prostate cancer, accurate prediction of the pathological stage before surgery is very important. Therefore, the aim of the present study was establishing the prostate-specific antigen (PSA) threshold nomogram to predict pathologically advanced prostate cancer using the novel method of area under the receiver operating characteristic curve boosting (AUCBoost).The medical records of patients with clinically localized prostate cancer who underwent robot-assisted radical prostatectomy were retrospectively reviewed. Multivariate logistic regression analysis was performed to identify clinical covariates significantly associated with pathological tumor stage ≥3a. The best combination of the variables was determined by validated values of the area under the curve (AUC). The optimal individualized PSA threshold values were developed using AUCBoost.In the multivariate logistic regression analysis, PSA, prostate volume, clinical tumor stage, Gleason Grade Group, the number of positive cores, and the percentage of positive cores were independent predictive factors for pathological tumor stage ≥3a. A combination model comprising PSA, prostate volume, clinical tumor stage, percent positive core, and Gleason Grade Group produced the highest AUC for predicting pathological tumor stage ≥3a (AUC = 0.777). The PSA threshold values for detecting pathological tumor stage ≥3a were calculated and a table of individualized PSA threshold nomogram was developed using AUCBoost.We developed a nomogram of the PSA threshold values for predicting adverse pathological tumor stages of prostate cancer using a novel statistical method. Further validation is necessary; however, the individualized PSA threshold nomogram may be useful in determining treatment strategies before surgery.

To determine prognostic factors associated with progression to castration-resistant prostate cancer following biochemical recurrence which is lethal prostate cancer and establish a risk stratification model of progression to castration-resistant prostate cancer. We retrospectively reviewed the data of 550 patients who experienced biochemical recurrence after radical prostatectomy. The endpoint of the present study was progression to castration-resistant prostate cancer. The actuarial probabilities of progression to castration-resistant prostate cancer-free survival were determined using Kaplan–Meier analysis. Univariate and multivariate Cox proportional hazards regression analyses were used to identify independent predictors of biochemical recurrence. Fifty-two patients experienced progression to castration-resistant prostate cancer during the follow-up period. The progression to castration-resistant prostate cancer-free survival rate after biochemical recurrence at 10 years was 76.8%. In multivariate analysis, pathological Gleason score ≥ 9, lymphovascular invasion, and prostate-specific antigen velocity ≥ 0.4 ng/mL/year were independent predictive factors for progression to castration-resistant prostate cancer. The patients were stratified into three groups using a risk stratification model incorporating these variables. The 10-year progression to castration-resistant prostate cancer-free survival rates were 96.7% in the low-risk group, 84.7% in the intermediate-risk group, and 24.5% in the high-risk group. The present results suggest that the pathological Gleason score, lymphovascular invasion, and prostate-specific antigen velocity were independent predictive factors for progression to castration-resistant prostate cancer. The risk stratification model established in the present study could be useful for patient counseling and in identifying patients with a poor prognosis.

Adult T-cell leukemia-lymphoma (ATL) is a distinct T-cell malignancy caused by human T-cell leukemia virus type-1; the prognosis is very poor. Mogamulizumab (Moga), an antibody drug for CC chemokine receptor type 4, has been introduced for the treatment of ATL. However, the prognosis of relapsed or refractory ATL remains poor and the characteristics of patients who derive clinical benefit from treatment with Moga remain poorly understood. We analyzed the associations of clinical factors with the outcome after Moga treatment. Forty-five patients treated with Moga monotherapy were evaluated. The median age of the patients was 69 years, and 40% were female. The median overall survival (OS) time was 17.6 months and the 2-year OS rate was 43.2%. Number of prior therapies and response to prior therapy were predictive clinical features in univariate analysis for OS. Performance status, corrected serum calcium level, serum lactate dehydrogenase level, Japan Clinical Oncology Group-prognostic index (PI), and simplified ATL-PI at Moga treatment were also associated with the prognosis after Moga monotherapy. Improved understanding of the clinical factors predicting the prognosis after Moga may contribute to improved treatment strategies for ATL.

The retrotransposon long interspersed nuclear element-1 (LINE-1) can autonomously increase its copy number within a host genome through the retrotransposition process. LINE-1 is active in the germline and in neural progenitor cells, and its somatic retrotransposition activity has a broad impact on neural development and susceptibility to neuropsychiatric disorders. The method to quantify the genomic copy number of LINE-1 would be important in unraveling the role of retrotransposition, especially in the brain. However, because of the species-specific evolution of LINE-1 sequences, methods for quantifying the copy number should be independently developed. Here, we developed a quantitative PCR (qPCR) assay to measure the copy number of active LINE-1 subfamilies in mice. Using the assay, we investigated aging-associated alterations of LINE-1 copy number in several brain regions in wild-type mice and Polg+/D257A mice as a model for accelerated aging. We found that aged Polg+/D257A mice showed higher levels of the type GfII LINE-1 in the basal ganglia than the wild-type mice did, highlighting the importance of assays that focus on an individual active LINE-1 subfamily.

Mogamulizumab (Mog) and lenalidomide (Len) are new therapeutic candidates for relapsed adult T-cell leukemia/lymphoma after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In the present study, we retrospectively analyzed 12 patients who received Mog or Len monotherapy for relapsed ATL after allo-HSCT. Eight and three patients received Mog and Len, respectively. The remaining patient received Mog for the first relapse and Len for the third relapse. A complete response was achieved by three and two patients who received Mog and Len, respectively, two and one of whom remained alive with a complete response for more than 20 months. In terms of adverse events, the emergence or progression of graft-versus-host disease was observed in three out of four patients treated with Len and in none of the patients treated with Mog. The development or progression of cytomegalovirus reactivation was detected in four out of eight patients treated with Mog and in none of those treated with Len. The present results suggest that Mog and Len would be promising treatment options for relapsed ATL after allo-HSCT and need to be selected based on adverse event profiles.

INTRODUCTION AND OBJECTIVES:Approximately 30% of men who undergo radical prostatectomy (RP) experience biochemical recurrence (BCR) within 5 years. However, since androgen deprivation therapy (ADT)...

Background Neutropenia is a major adverse event of docetaxel-based chemotherapy. The present study was undertaken to evaluate the incidence of neutropenia and to develop a nomogram for predicting Grade 4 neutropenia during the first cycle of docetaxel-based chemotherapy in patients with castration-resistant prostate cancer (CRPC). Patients and Methods This study included 112 patients with CRPC treated with docetaxel-based systemic chemotherapy. We evaluated the incidence and risk factors for Grade 4 neutropenia in the first cycle of chemotherapy. Results Sixty-two of 112 patients (55.4%) developed Grade 4 neutropenia in the first cycle of docetaxel-based chemotherapy. There were significant differences in age, baseline white blood cell count, and baseline neutrophil count between patients with non-Grade 4 neutropenia and those with Grade 4 neutropenia in univariate analyses. The serum prostate-specific antigen level, hemoglobin level, creatinine, albumin, Eastern Cooperative Oncology Group performance status, metastatic sites, extent of disease, and history of external beam radiotherapy to the prostate were not significantly different between the 2 groups. Multivariate logistic regression analysis showed that age (odds ratio [OR], 1.08; P = .019) and baseline neutrophil counts (OR, 0.79; P = .045) were significant independent risk factors for severe neutropenia. A nomogram and a calibration plot on the basis of these results were developed from a multivariate logistic regression analysis to predict the probability of Grade 4 neutropenia. Conclusion Age and baseline neutrophil counts were significant independent risk factors for Grade 4 neutropenia. The nomogram to predict it provides useful information for the management of patients with CRPC treated with docetaxel chemotherapy.

Objectives To investigate the predictive values of perioperative factors and to develop a nomogram for intravesical recurrence after radical nephroureterectomy in patients with upper urinary tract urothelial carcinoma. Methods A retrospective analysis of 144 patients who underwent radical nephroureterectomy from 1996 to 2014 was carried out. The actuarial probabilities of the intravesical recurrence-free survival rate were calculated using the Kaplan–Meier method. Prognostic indicators for intravesical recurrence were identified using competing-risks regression analyses. Results Intravesical recurrence occurred in 63 patients during the follow-up period. The intravesical recurrence-free survival rates at 1, 3, and 5 years were 65.7%, 50.6% and 47.1%, respectively. In univariate analysis, the presence of gross hematuria (P = 0.028) and the preoperative serum creatinine level (P = 0.033) were significantly associated with intravesical recurrence. In multivariate analysis, the presence of gross hematuria (subdistribution hazard ratio 2.03, 95% CI 1.145–3.496; P = 0.013) and the preoperative serum creatinine level (subdistribution hazard ratio 3.15, 95% CI 1.161–3.534; P = 0.021) were independent predictors for intravesical recurrence after radical nephroureterectomy. Accordingly, a nomogram based on the model was developed. The concordance index of this model was 0.632. Conclusion The presence of gross hematuria and preoperative serum creatinine levels seem to be independent predictors for intravesical recurrence after radical nephroureterectomy. Our nomogram developed based on these factors might aid in appropriate patient selection for clinical trials of novel therapeutic interventions, including administration of intravesical chemotherapy.

To investigate the prognostic significance of sarcopenia on long-term outcomes in patients with bladder cancer after radical cystectomy (RC). We retrospectively reviewed 136 patients undergoing RC for urothelial carcinoma at our institution. Prognostic impact of the preoperative clinical, laboratory, and radiologic parameters were evaluated by Cox proportional hazard model analyses, and a nomogram was developed to predict cancer-specific survival (CSS) after RC. The mean follow-up was 46.7 months. Patients with sarcopenia had a significantly shorter CSS than those without sarcopenia. On univariate Cox analysis, clinical T stage, histology of transurethral resection of bladder tumor (TURBT) specimen, pretreatment hemoglobin, pretreatment neutrophil-to-lymphocyte ratio (NLR), pretreatment serum C-reactive protein level, pretreatment serum albumin level, presence of hydronephrosis, and presence of sarcopenia were associated with significantly worse CSS. On multivariate Cox stepwise analysis, sarcopenia (hazard rate [HR] = 2.3, p = 0.015), clinical T stage (cT4: HR = 5.3; p = 0.0096), presence of hydronephrosis (HR = 2.0; p = 0.033), histology of TURBT specimen (HR = 2.2, p = 0.044), and NLR (HR = 1.3; p = 0.0048) were significant independent predictors of an unfavorable prognosis Based on the results of the multivariate analysis, we developed a nomogram to predict 1-, 3-, and 5-year CSS after RC. Sarcopenia, clinical T stage, presence of hydronephrosis, histology of TURBT specimen, and NLR are novel preoperative prognostic factors even after adjustment for other known preoperative predictors in patients undergoing RC for bladder cancer.

The purpose of the present study was to evaluate the wear of four different ceramics and human enamel. The ceramics used were lithium disilicate glass (e.max Press), leucite-reinforced glass (GN-Ceram), yttria-stabilized zirconia (Aadva Zr), and feldspathic porcelain (Porcelain AAA). Hemispherical styli were fabricated with these ceramics and with tooth enamel. Flattened enamel was used for antagonistic specimens. After 100,000 wear cycles of a two-body wear test, the height and volume losses of the styli and enamel antagonists were determined. The mean and standard deviation for eight specimens were calculated and statistically analyzed using a non-parametric (Steel-Dwass) test (α = 0.05). GN-Ceram exhibited greater stylus height and volume losses than did Porcelain AAA. E.max Press, Porcelain AAA, and enamel styli showed no significant differences, and Aadva Zr exhibited the smallest stylus height and volume losses. The wear of the enamel antagonist was not significantly different among GN-Ceram, e.max Press, Porcelain AAA, and enamel styli. Aadva Zr resulted in significantly lower wear values of the enamel antagonist than did GN-Ceram, Porcelain AAA, and enamel styli. In conclusion, leucite-reinforced glass, lithium disilicate glass, and feldspathic porcelain showed wear values closer to those for human enamel than did yttria-stabilized zirconia.

A 17-year-old male underwent a second bone marrow transplantation using a 6/8 allele HLA-matched unrelated donor. On day 100 after transplantation, steroid treatment for chronic graft-versus-host disease (GVHD) was started. On day 766, the patient experienced general fatigue, followed by double vision, ptosis, and dysphagia on day 810. Based on the positivity of the acetylcholine receptor antibody and a waning electromyography pattern, he was diagnosed with GVHD-related myasthenia gravis (MG). On day 861, we initiated plasmapheresis (PE), followed by the administration of intravenous immunoglobulin (IVIg) ; this treatment attenuated the bulbar symptoms of MG. Although the steroid treatment was continued, we restarted the administration of tacrolimus. On day 2,739 after transplantation, we stopped the steroid treatment, and the patient remained in remission for MG following the cessation of the steroid treatment on day 2,897. This case suggests that PE followed by IVIg could be an effective therapeutic alternative for MG associated with GVHD.

The aim of this study was to investigate the association between serum total cholesterol (TC) level and biochemical recurrence (BCR) following radical prostatectomy (RP). The study included 562 patients with T1-3N0M0 prostate cancer, who underwent RP at our institution between 2002 and 2010. No patients received neoadjuvant and/or adjuvant therapy. The associations between preoperative TC level, clinicopathological factors and BCR were assessed using univariate and multivariate analyses. During follow-up (mean, 54.0 months), 168 patients (168/562, 29.9%) experienced BCR, with a 5-year BCR-free rate of 67.2%. Of the clinicopathological characteristics investigated, statin use and lymphovascular invasion (LVI) status were associated with lower TC level (P=0.003 and P=0.014, respectively). In the univariate analysis, a higher serum prostate-specific antigen (PSA) level at diagnosis, extracapsular extension, positive surgical margin, seminal vesicle invasion, LVI, perineural invasion, higher Gleason score (GS ≥8) based on the RP specimen, increased body mass index, and low preoperative TC level, were significantly associated with BCR. In the multivariate analysis, the TC level was an independent predictor of BCR (hazard ratio = 0.925 per 10 mg/dl; 95% confidence interval: 0.879-0.973; P=0.003), as was the serum PSA level, extracapsular extension, positive surgical margin and the GS. Low preoperative serum TC levels were associated with an increased risk of BCR among prostate cancer patients who underwent RP. Our findings suggest that the preoperative serum TC level may provide important clinical information that may prove to be useful in patient counseling.

Background: The purpose of this study was to validate the treatment strategy for a cohort of Japanese patients with very low-risk (VLR) and low-risk (LR) prostate cancer according to the National Comprehensive Cancer Network (NCCN) guidelines. Methods: We studied 751 patients with T1- 3N0M0 prostate cancer treated with radical prostatectomy at our institution between 2000 and 2012. Patients with neoadjuvant treatments were excluded. We retrospectively reviewed the clinical and pathological outcomes for patients with VLR or LR prostate cancers that were classified by NCCN guidelines. Results: We identified 45 patients with VLR and 137 with LR prostate cancer. Non-biochemical recurrence rate at 5-year for 45 patients with VLR was 86.9% and 81.2% for 137 patients with LR (p = 0.56). However, none of the 19 patients >65 years old with VLR progressed, while 19% of 26 patients ≤65 years old with VLR cancer, 14% of patients >65 years old with LR cancer, and 17% of patients ≤65 years old with LR cancer progressed during the follow-up period (p = 0.04, p = 0.04 and p = 0.05, respectively). In analyses of prostatectomy specimens, both VLR and LR had similarly favorable outcomes, but patients >65 years old with VLR had the smallest tumors, with a mean of 5 mm in diameter. Conclusions: Our results support the treatment strategy of the NCCN that patients with VLR cancer and age >65 years old are good candidates for active surveillance, and that other treatment options—including active surveillance and aggressive treatments—can be applied to the remaining patients with VLR or LR cancers.

To identify preoperative predictive factors for biochemical recurrence (BCR) and to further stratify its risk in high-risk localized prostate cancer patients receiving radical prostatectomy (RP). Subjects included 195 high-risk prostate cancer patients undergoing RP from 2000 to 2012. RP consisted of retropubic radical prostatectomy and robot-assisted radical prostatectomy, involving 84 cases and 111 cases, respectively. BCR was defined as a prostate serum antigen (PSA) level ≥0.2 ng/mL. BCR-free survival (BCRFS) was calculated using the Kaplan–Meier method. Preoperative predictors of BCR were assessed with Cox’s proportional hazard regression analysis. Eighty-nine patients (45.6 %) experienced recurrence. BCRFS rates 3 and 5 years after RP were 58 and 50 %, respectively. Prostate volume, transition zone volume, and Gleason score were not significantly associated with BCR. Patients with higher preoperative PSA, PSA density (PSAD), PSA density of the transition zone, percentage of positive cores (PPC), and PPC from the dominant side showed significantly lower BCRFS. The PPC from the dominant side and PSAD were significant independent prognostic factors for BCR. Using these variables, the hazard ratio of BCR could be calculated and patients stratified into three risk groups. The 5-year BCRFS rates for Groups 1, 2, and 3 were 64.9 %, 48.1 %, and 21.3 %, respectively. Patients with high-risk localized prostate cancer as currently defined do not have uniformly poor prognosis after RP. PPC from the dominant side and PSAD are significant predictors of BCR. These factors can identify high-risk patients with very poor prognosis.

To assess the impact of preoperatively estimated prostate volume (PV) using transrectal ultrasonography (TRUS) on surgical and oncological outcomes in robot-assisted radical prostatectomy (RARP).We analyzed the experience of a single surgeon at our hospital who performed 436 RARPs without neoadjuvant hormone therapy between August 2006 and December 2013. Patients were divided into three groups according to their preoperative PV calculated using TRUS (PV ≤ 20 cm(3): group 1, n = 61; 20 PV 50 cm(3): group 2, n = 303; PV ≥ 50 cm(3): group 3, n = 72).Blood loss was significantly higher in group 3 than in group 1 and group 2. In stage pT2 patients, the rate of positive surgical margin (PSM) was significantly lower in group 3 than in group 1. In addition, perioperative complications significantly increased with increasing PV, while the extraprostatic extension (EPE) rate significantly decreased with increasing PV. The preoperative biopsy Gleason score, prostate-specific antigen (PSA) density, and clinical T2 stage were inversely correlated with increasing PV. Biochemical recurrence-free survival after RARP was significantly lower in group 1 than in groups 2 and 3.A large prostate size was significantly associated with increased blood loss and a higher rate of perioperative complications. A small prostate size was associated with a higher PSM rate, PSA density, Gleason score, EPE rate, and biochemical recurrence rate. These results suggest that RARP was technically challenging in patients with large prostates, whereas small prostates were associated with unfavorable oncological outcomes.

Objectives To investigate the prognostic value of preoperative pyuria in patients with non-muscle-invasive bladder cancer. Methods We retrospectively reviewed data from 237 patients diagnosed with non-muscle-invasive bladder cancer. Pyuria was defined as urine containing ≥5 white blood cells per high power field. The association between clinicopathological factors and recurrence was assessed by Cox univariate and multivariate analyses. Results Preoperative pyuria was found in 116 (49.0%) patients. Pyuria was significantly associated with advanced age, positive cytology, multiple tumors, large tumor size, non-papillary tumors, T1 tumors and high-grade tumors. In univariate analysis of the entire patient population, pyuria, positive urine cytology, multiple tumors, pT1 tumors and no bacillus Calmette–Guerin were significantly associated with recurrence. Multivariate analysis showed that pyuria was an independent predictor of recurrence (hazard ratio 3.332, 95% confidence interval 2.052–5.410; P

Adult T-cell leukemia–lymphoma (ATL) is an intractable hematopoietic malignancy with a very poor prognosis. Although improved responses have been achieved through intensive chemotherapy in newly diagnosed patients with aggressive ATL, most patients suffer from relapse or disease recurrence, and an effective salvage therapy, especially for candidates for allogeneic hematopoietic stem cell transplantation (allo-HSCT), is yet to be established. The efficacy of the EPOCH regimen has been reported for several lymphoid malignancies; however, its efficacy for ATL has not been sufficiently evaluated. Here, we report results of a study of the EPOCH regimen as a salvage therapy for ATL. We retrospectively analyzed patients with relapsed or refractory ATL treated in our institution, with EPOCH as a first salvage therapy. Fourteen patients with a median age of 58 years were analyzed, among whom eight achieved a response, including a complete response in one patient and partial responses in seven. Seven patients underwent allo-HSCT after EPOCH therapy; however, the median overall survival (OS) could not be determined, whereas OS at 2 years after allo-HSCT was estimated to be 85.7%. These results suggest that EPOCH is an option for salvage therapy in patients with ATL, including candidates for allo-HSCT.

Urinary incontinence is one of the most bothersome adversities after robot-assisted radical prostatectomy (RARP). The aim of this study was to investigate the urinary continence recovery and the effect of various surgical techniques.We previously reported that posterior rhabdosphincter reconstruction and nerve-sparing were independent predictors of urinary continence recovery 1 month after catheter removal in 199 patients who underwent RARP. Retrospectively, we further reviewed those 199 patients for urinary continence recovery at 3 months or later after RARP. The relationships of urinary continence with perioperative findings, including surgical procedures, were evaluated at 3 to 12 months after RARP. The Fisher exact test and Mann-Whitney rank sum test were used for evaluating variables between the groups. Multivariate logistic regression analysis was performed to investigate the association between urinary continence and perioperative factors.On univariate analyses, surgeon experience, lateral bladder neck preservation (BNP), anterior reconstruction, and posterior reconstruction were significantly associated with urinary continence recovery 3 months after RARP, but only lateral BNP was independently associated with urinary continence recovery in a multivariate analysis. Similarly, on univariate analyses, surgeon experience, lateral BNP, and posterior reconstruction were significantly associated with continence recovery at 6 months or later after surgery. However, multivariate analyses showed that only lateral BNP was significantly associated with urinary continence recovery 6 months or later after surgery.Although the lateral BNP technique did not affect immediate urinary continence recovery, this procedure was significantly associated with continence recovery 3 months or later after RARP.

Purpose To investigate the impact of the time interval (TI) between prostate biopsy and robot-assisted radical prostatectomy (RARP) on the risk of biochemical recurrence (BCR). Methods We retrospectively reviewed the medical records of 793 consecutive patients who were treated with RARP at our institution. Patients were divided into three groups, according to TI, to compare BCR-free survival (BCRFS) rates: Group 1 (n = 196), TI < 3 months; Group 2 (n = 513), 3 ≤ TI < 6 months; Group 3 (n = 84), TI ≥ 6 months. Eighty-three patients with TI ≥ 6 months were matched with an equal number of patients with TI < 6 months based on propensity scores by using four preoperative factors: prostate-specific antigen (PSA), primary (pGS) and secondary (sGS) Gleason score and positive prostate biopsy. Results The 5-year BCRFS rates for TI Groups 1, 2, and 3 were 76%, 80.7% and 82.6% (P = 0.99), respectively. The multivariate analysis revealed that PSA, pGS, sGS and a positive prostate biopsy were independent preoperative risk factors for BCR. The propensity adjusted 5-year BCRFS for patients with TI ≥ 6 months was 84.0%. This was not worse than that of patients with TI < 6 months (71.0%, P = 0.18). Conclusions In our cohorts, a delay in the time from biopsy to RARP did not significantly affect recurrence. Therefore, hasty treatment decisions are unnecessary for at least 6 months after diagnosis of early prostate cancer.

Objectives To examine biochemical recurrence after robot-assisted radical prostatectomy in Japanese patients, and to develop a risk stratification model for biochemical recurrence. Methods The study cohort consisted of 784 patients with localized prostate cancer who underwent robot-assisted radical prostatectomy without neoadjuvant or adjuvant endocrine therapy. The relationships of biochemical recurrence with perioperative findings were evaluated. The prognostic factors for biochemical recurrence-free survival were evaluated using Cox proportional hazard model analyses. Results During the follow-up period, 80 patients showed biochemical recurrence. The biochemical recurrence-free survival rates at 1, 3, and 5 years were 92.2%, 85.2% and 80.1%, respectively. In univariate analysis, the prostate-specific antigen level, prostate-specific antigen density, biopsy Gleason score, percent positive core, pathological T stage, pathological Gleason score, lymphovascular invasion, perineural invasion and positive surgical margin were significantly associated with biochemical recurrence. In multivariate analysis, prostate-specific antigen density ≥0.4 (P = 0.0011), pathological T stage ≥3a (P = 0.002), pathological Gleason score ≥8 (P = 0.007) and positive surgical margin (P

We present a case of a 67-year-old man with intussusception of the right ureter associated with a fibroepithelial polyp. The concentric sign and line sign are characteristic radiological findings in intussusception, and these findings could be seen in the present case. Although this entity is rare, its radiological findings are specific. Multidetector row computed tomography and its multiplanar reconstruction make the diagnosis feasible, although the qualitative diagnosis of the tumor was difficult.

To investigate the clinical implication of preoperative serum total cholesterol (TC) level in patients with clear cell renal cell carcinoma (RCC).The records of 364 patients with clear cell RCC who had undergone nephrectomy were retrospectively reviewed. The association among preoperative TC level, clinicopathologic factors, and oncological outcome in terms of cancer-specific survival (CSS) and recurrence-free survival period was analyzed by univariate and multivariate analyses.As a continuous variable, lower serum TC level was found to be significantly associated with male sex, symptomatic tumor, advanced TNM stage, higher nuclear grade, microscopic venous invasion, poor Eastern Cooperative Oncology Group Performance Status, larger tumor size, elevated C-reactive protein level, and lower hemoglobin level. Univariate analysis showed that relatively lower preoperative serum TC level was associated with lower recurrence-free survival (P = .040) and CSS (P .001) rates. Multivariate analysis indicated that in addition to pT stage, M stage, nuclear grade, and Eastern Cooperative Oncology Group Performance Status, serum TC level (hazard ratio, 0.988 per mg/dL; 95% confidence interval, 0.980-0.998; P = .019) was an independent predictor of CSS.Low preoperative serum TC level is associated with worse prognosis in patients with clear cell RCC. Consideration of preoperative serum TC level might thus provide additional prognostic information for patients with clear cell RCC.

An appropriate trigger for BCR-ABL1 mutation analysis has not yet been established in unselected cohorts of chronic-phase chronic myelogenous leukemia patients. We examined 92 patients after 12 months of tyrosine kinase inhibitor (TKI) treatment in Nagasaki Prefecture, Japan. Univariate analysis revealed that significant factors associated with not attaining a major molecular response (MMR) were the presence of the minor BCR-ABL1 fusion gene, a low daily dose of TKI, and the emergence of BCR-ABL1 kinase domain mutations conferring resistance to imatinib. Factors associated with the loss of sustained MMR were a low daily dose of TKI and the emergence of alternatively spliced BCR-ABL1 mRNA with a 35-nucleotide insertion. Taken together, our results suggest that the search for BCR-ABL1 mutations should be initiated if patients have not achieved MMR following 12 months of TKI treatment., Leukemia Research, 38(1), pp.76-83; 2014

Objective To develop a nomogram based on postoperative factors and prostate-specific antigen levels to predict the non-biochemical recurrence rate after radical prostatectomy in a Japanese cohort. Methods A total of 606 Japanese patients with T1-3N0M0 prostate cancer who underwent radical prostatectomy and pelvic lymph node dissection at Tokyo Medical University hospital from 2000 to 2010 were studied. A nomogram was constructed based on Cox hazard regression analysis evaluating the prognostic significance of serum prostate-specific antigen and pathological factors in the radical prostatectomy specimens. The discriminating ability of the nomogram was assessed by the concordance index (C-index), and the predicted and actual outcomes were compared with a bootstrapped calibration plot. Results With a mean follow up of 60.0 months, a total of 187 patients (30.9%) experienced biochemical recurrence, with a 5-year non-biochemical recurrence rate of 72.3%. Based on a Cox hazard regression model, a nomogram was constructed to predict non-biochemical recurrence using serum prostate-specific antigen level and pathological features in radical prostatectomy specimens. The concordance index was 0.77, and the calibration plots appeared to be accurate. Conclusions The postoperative nomogram described here can provide valuable information regarding the need for adjuvant/salvage radiation or hormonal therapy in patients after radical prostatectomy.

The aim of the present study was to investigate the learning curve and perioperative outcomes in 200 consecutive patients with prostate cancer who underwent robot-assisted radical prostatectomy (RARP).Between August 2006 and August 2011, 200 patients with prostate cancer underwent RARP and were enrolled in this study. We prospectively collected the demographic data and analyzed the pathologic and functional outcomes. The operative outcomes analyzed were total operative time, estimated blood loss (EBL), positive surgical margin (PSM), incontinence, and perioperative complications. We also evaluated the relationship between the surgeon's experience and operative variables.The sloping learning curve for this surgeon showed that total operative time was strongly correlated with the accumulation of experience for the initial 25 cases (|rs|=0.71, P0.001). The average EBL was not strongly correlated with additional experience (|rs|0.7). The PSM rate for the first 50 cases was significantly higher than that of the next 150 cases (34.8% vs 19.4%, P=0.035). The complication rate among the first 50 patients was significantly higher than that among the remaining 150 patients (32% vs 12.7%, P=0.002). The incontinence rate at 12 months was significantly higher for the first 100 cases compared with that for the next 100 cases (9.0% vs 1.0%, P=0.009). For the surgeon to optimize total operative time, PSM rate, complication rate, and incontinence rate, slope learning curves of 25, 50, 50, and 100 cases were needed.The functional and pathologic results of this minimally invasive procedure seemed to be promising. Distinct learning curves were observed with respect to operative time, PSM, complication rate, and incontinence rate. Exposure to 100 surgeries would be necessary for a surgeon to adequately master the required skills.

We investigated oncological outcomes in Japanese patients who underwent robot-assisted radical prostatectomy (RARP). This study included 389 patients who underwent RARP at a single institution with a follow-up period of at least 1 year. Preoperative findings were compared with biochemical recurrence (BCR). Predictors of BCR-free survival (BCRFS) were evaluated by univariate and multivariate Cox proportional hazard model analyses, and a risk stratification model based on the relative risks of BCR was established. Fifty incidences of BCR were noted during a median follow-up period of 28.7 months (range, 12.1–80.0 months). The BCRFS rate for the entire cohort at the median follow-up time was 85.9 %; the 1-, 3-, and 5-year estimates were 91.0, 85.1, and 81.1 %, respectively. From univariate analyses, prostate-specific antigen (PSA), PSA density, biopsy Gleason score, and percent positive core were significantly associated with BCR. Multivariate analysis showed that PSA [hazard ratio (HR), 2.75; p = 0.001], percent positive core (HR, 2.22; p = 0.001), and biopsy Gleason score (HR, 2.61; p = 0.007) were independent predictors of BCR. This study at a single Japanese center demonstrates that RARP provides a satisfactory BCRFS rate. This report provides a framework with which to estimate oncological outcomes in patients who underwent RARP for localized prostate cancer. Our results support the increased use of RARP for the treatment of localized prostate cancer in Japan.

Few studies have evaluated changes in erectile function with time before and after prostate brachytherapy using the International Index of Erectile Function-15, a sensitive, validated tool for assessing male sexual dysfunction. In this prospective study we evaluated the natural history of erectile function after prostate brachytherapy without supplemental therapy (external beam radiotherapy, phosphodiesterase-5 inhibitors or androgen deprivation therapy) using the International Index of Erectile Function-15.We identified 119 patients who were followed at least 12 months after prostate brachytherapy between 2004 and 2010. Sexual and erectile function status were assessed before brachytherapy (baseline), and 3, 6, 12, 18, 24 and 36 months postoperatively using the International Index of Erectile Function-15.Mean total International Index of Erectile Function-15 score, and scores on the erectile function, orgasmic function, sexual desire and intercourse satisfaction domains 3 months after brachytherapy were significantly lower than at baseline (p0.05). They remained lower until 36 months after prostate brachytherapy. Erectile function was maintained 12 months after brachytherapy in 16 of the 48 men (33.3%) with a baseline erectile function domain score of 11 or greater. There was no significant difference in clinical features except the age of patients who maintained the erectile function domain score and their counterparts 12 months after brachytherapy. Multivariate analysis revealed that age 70 years or greater was the only predictive factor for deteriorating erectile function after brachytherapy (p = 0.035).Findings indicate a global decrease in all domains of the International Index of Erectile Function-15 score 12 months after prostate brachytherapy. Also, patient age may influence the preservation of brachytherapy related potency.

Objective Positive surgical margin after radical prostatectomy has been shown to be an independent predictive factor for biochemical and local recurrence in patients with prostate cancer. The present study was undertaken to identify predictive factors for positive surgical margin after robot-assisted radical prostatectomy in Japanese patients. Methods Between August 2006 and September 2011, a cohort of 244 men underwent robot-assisted radical prostatectomy carried out by a single surgeon. Univariate and multivariate logistic regression analyses were carried out to identify clinical covariates significantly associated with an increased positive surgical margin. The preoperative variables included age, body mass index, prostate-specific antigen level, prostate-specific antigen density, clinical T stage, prostate volume, surgeon volume, number of positive cores and percentage of positive cores. Results In the univariate analyses, serum prostate-specific antigen level, prostate-specific antigen density and surgeon volume were significantly associated with positive surgical margin. In the multivariate analysis, prostate-specific antigen density (hazard ratio 3.13, 95% confidence interval 1.57–6.24; P = 0.001) and surgeon volume (hazard ratio 2.15, 95% confidence interval 1.06–4.35; P = 0.034) were independent predictive factors for positive surgical margin. Using these two independent factors, we divided the patients into four groups and calculated the predictive probability of positive surgical margin. The predictive probability for positive surgical margin in each group was well correlated with the rates at 10.8% and 10.2%, 19.8% and 20.0%, 26.4% and 26.4%, an 43.5% and 43.3%, respectively. Conclusion Prostate-specific antigen density and surgeon volume are independent predictors of positive surgical margin after robot-assisted radical prostatectomy. A combination of these two factors can provide useful information about positive surgical margins.

Purpose We aimed to determine which of the following magnetic resonance (MR) imaging sequences is most effective for detecting prostate cancer: T2-weighted (T2W), dynamic contrast-enhanced (DCE) T1-weighted (T1W), or diffusion-weighted (DWI) imaging or apparent diffusion coefficient (ADC) mapping. Materials and methods We included 37 male patients with prostate cancer who underwent MR imaging before radical prostatectomy in this retrospective study. Sixty-four foci (>5 mm in size; 35 in the peripheral zone [PZ], 29 in the transitional zone [TZ]) were histopathologically determined to be prostate cancer. We determined the capacity of T2W, DCE-T1W, DWI, ADC mapping alone, and the combination of ADC mapping with DWI, and conventional MR sequences to detect prostate cancer, including their sensitivity and positive predictive value (PPV), with reference to the results obtained in histopathological examinations of whole-mount sections. Results In the PZ, sensitivities were 31.4% (T2W), 37.1% (DCE-T1W), 51.4% (DWI), and 71.4% (ADC mapping); PPVs were 78.6% (T2W), 92.9% (DCE-T1W), 94.7% (DWI), and 96.0% (ADC mapping). Sensitivity was significantly higher of ADC mapping than other sequences. In the TZ, sensitivities were 55.1% (T2W), 44.8% (DCE-T1W), 82.8% (DWI), and 89.7% (ADC mapping); PPVs were 64.0% (T2W), 46.4% (DCE-T1W), 70.6% (DWI), and 72.2% (ADC mapping). Sensitivity was significantly higher of ADC mapping and DWI than conventional MR imaging, but there was no significant correlation between DWI/ADC mapping and T2W/DCE-T1W with respect to PPVs. Combining sequences did not improve sensitivity; only the PPV in the TZ improved when ADC mapping was combined with DCE-T1W. Conclusion ADC mapping is the most effective standard MR imaging tool for detecting prostate cancer. The addition of DCE-T1W may improve the PPV of ADC mapping for diagnosing cancer in the TZ.

in theACTand13.7months in thenon-ACTgroup (p1⁄40.78).ACTremained an insignificant predictor for RFS after adjusting for pT, pN and margin status (HR: 0.89, 95%CI: 0.48-1.68]). CSS was 23 and 22 months in the respective groups (p1⁄40.65) and remained insignificant after adjusting for pathologic confounders (HR: 0.67, [95%CI: 0.34-1.28]). The eight patients who received cisplatin-based chemotherapy in both neoadjuvant and adjuvant settings had the highest median RFS of 23.2 months. CONCLUSIONS: AC in this retrospective cohort of pT3-4 and/or pN+ did identify a subset with better median RFS. However, the choice of AC regimens, and incorporation of newer drugs, particularly beyond useof conventional cytotoxic drugs, in both adjuvant and neoadjuvant contexts is a key direction for improving outcomes in this high risk patient group.

To investigate the clinical implication of legumain, an asparaginyl endopeptidase that is highly expressed in several types of cancer, expression in prostate cancer.Legumain expression in prostate cancer cell lines was determined by real-time reverse transcriptase PCR and Western blot. Furthermore, legumain expression in 88 prostatectomy specimens was evaluated by immunohistochemistry. The association between legumain expression and clinicopathological factors was analyzed.Legumain expression was confirmed at the mRNA and protein levels in all the cells. Although all the cancer tissues were positive for legumain, 2 staining patterns were observed in the cytoplasm: diffuse cytoplasmic and vesicular positivity. The rates of Gleason score ≥8, extracapsular extension, and perineural invasion in the group with vesicular staining were significantly higher than those in the diffuse cytoplasmic group (p0.05). The maximum size of the tumor with vesicular staining was significantly greater than that of the tumor with diffuse cytoplasmic staining (p = 0.0302). The 5-year biochemical recurrence-free rate in the patients with vesicular legumain staining was 53.2%; this rate was significantly lower than that (78.8%) in the patients with diffuse cytoplasmic staining (p = 0.0269).Tumors that showed a vesicular staining pattern of legumain had the potential of being highly invasive and aggressive in patients with prostate cancer who were treated with radical prostatectomy. This suggests that legumain might contribute to the invasiveness and aggressiveness of prostate cancer.

Purpose To report a rare case of seed migration to a left varicocele after transperineal interstitial prostate brachytherapy with loose iodine-125 (125I) seeds. Methods and Materials A 73-year-old man presented with a serum prostate-specific antigen level of 5.21 ng/mL, Gleason score of 7 (3 + 4), and clinical T1c adenocarcinoma of the prostate. The patient underwent transperineal interstitial prostate brachytherapy with loose 125I seeds followed by external beam radiation therapy. Two weeks after seed implantation, a followup pelvic radiograph was obtained. One month after seed implantation, a pelvic computed tomography scan for postimplant dosimetric analysis was carried out. Subsequent ultrasound examination of the scrotum was undertaken. Results Two weeks after seed implantation, an anteroposterior pelvic radiograph showed that a migrated seed was overlapped by the scrotum. Postimplant pelvic computed tomography revealed that a seed had migrated to the left side of the scrotum. Subsequent ultrasound examination of the scrotum revealed that the patient had a left varicocele to which the seed had migrated. The patient had no symptoms related to the migrated seed. Conclusions This is the first report of seed migration to a left varicocele after transperineal interstitial prostate brachytherapy with loose 125I seeds. For the present case, we suggest that the seed moved from the prostate to the left varicocele through the pelvic veins, bypassing the systemic circulation.

Objective To investigate preoperative predictors of ureteral involvement of bladder malignancy and to develop a novel preoperative model for the prediction of ureteral involvement in bladder cancer patients undergoing radical cystectomy. Methods This study included 197 consecutive bladder cancer patients treated with radical cystectomy. The correlations of preoperative factors with ureteral involvement were analyzed by univariate analysis with Pearson's χ2-test and multivariate logistic regression analysis with a stepwise selection procedure. Results Positive ureteral involvement was observed in 38 (19.3%) patients. Tumor location (involvement of the vesical trigone), clinical T stage (≥ cT3) and the number of tumors (≥3), but not sex, tumor grade and histological features determined by transurethral resection of bladder tumor, tumor size, shape of tumor, concomitant presence of carcinoma in situ, preoperative intravesical therapy, number of transurethral resection of bladder tumor procedures or the presence of hydronephrosis were significantly associated with ureteral involvement in the univariate analysis. Multivariate logistic regression analysis confirmed that the aforementioned three significant factors identified in the univariate analysis were significant independent predictors of ureteral involvement. The probability of ureteral involvement estimated by a combination of these three parameters was well correlated with the real incidence (R = 0.904, P = 0.0021). Conclusions Tumor location (involvement of vesical trigone), clinical T stage (≥cT3) and the number of tumors (≥3) are significant independent preoperative predictors of ureteral involvement of malignancy in bladder cancer patients undergoing radical cystectomy. Our predictive model might be useful for preoperative prediction of ureteral tumor involvement.

Background: Inducible activation of nuclear factor (NF)-κB is one of the principal mechanisms through which resistant prostate cancer cells are protected from radiotherapy. We hypothesised that inactivation of inducible NF-κB with a novel NF-κB inhibitor, DHMEQ, would increase the therapeutic effects of radiotherapy. Methods: PC-3 and LNCaP cells were exposed to irradiation and/or DHMEQ. Cell viability, cell cycle analysis, western blotting assay, and NF-κB activity were measured. The antitumour effect of irradiation combined with DHMEQ in vivo was also assessed. Results: The combination of DHMEQ with irradiation resulted in cell growth inhibition and G2/M arrest relative to treatment with irradiation alone. Inducible NF-κB activity by irradiation was inhibited by DHMEQ treatment. The expression of p53 and p21 in LNCaP, and of 14-3-3σ in PC-3 cells, was increased in the combination treatment. In the in vivo study, 64 days after the start of treatment, tumour size was 85.1%, 77.1%, and 64.7% smaller in the combination treatment group than that of the untreated control, DHMEQ-treated alone, and irradiation alone groups, respectively. Conclusion: Blockade of NF-κB activity induced by radiation with DHMEQ could overcome radio-resistant responses and may become a new therapeutic modality for treating prostate cancer.