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To stratify the heterogeneity of prostate cancer (PCa) with seminal vesicle invasion (SVI) immunologically after radical prostatectomy focusing on the tumor microenvironment. We retrospectively reviewed the clinicopathological data of 71 PCa patients with SVI, which is known as a factor of very high-risk PCa. Preoperative clinical variables and postoperative pathological variables were evaluated as predictors of biochemical recurrence (BCR) with a multivariate logistic regression. Immune cell infiltration including the CD8-positive cell (CD8+ cell) and CD204-positive M2-like macrophage (CD204+ cell) was investigated by immunohistochemistry. The cumulative incidence and risk of BCR were assessed with a Kaplan–Meier analysis and competing risks regression. A higher CD8+ cell count in the SVI area significantly indicated a favorable prognosis for cancers with SVI (p = 0.004). A lower CD204+ cell count in the SVI area also significantly indicated a favorable prognosis for cancers with SVI (p = 0.004). Furthermore, the combination of the CD8+ and CD204+ cell infiltration ratio of the SVI area to the main tumor area was a significant factor for BCR in the patients with the PCa with SVI (p = 0.001). In PCa patients with SVI, the combination of CD8+ and CD204+ cell infiltration is useful to predict the prognosis.

OBJECTIVE Pheochromocytoma is a rare neuroendocrine tumour that secretes catecholamines and originates in the adrenal gland. Although surgical resection is the only curative therapy for pheochromocytoma, it is associated with a risk of haemodynamic instability (HDI), such as extremely high blood pressure and/or post tumour removal hypotension and shock. We investigated the risk factors for HDI during pheochromocytoma surgery. DESIGN AND PATIENTS Eighty-two patients who underwent laparoscopic adrenalectomy for pheochromocytoma between July 2002 and February 2020 were examined. We excluded 3 patients with bilateral disease and 11 without detailed 24 h urinary data. We defined HDI as systolic blood pressure ≥ 200 or

Background It currently remains unclear whether the location of primary tumours affects the clinical outcomes of patients with locally advanced urothelial carcinoma in the urinary tract. The aim of the present study was to compare prognostic differences between bladder urothelial carcinoma and upper tract urothelial carcinoma, particularly pT3 or higher tumours. Methods In total, 307 patients with pT3 or higher urothelial carcinoma without distant metastasis who underwent radical cystectomy for bladder urothelial carcinoma (N = 127, 41.4%) or radical nephroureterectomy for upper tract urothelial carcinoma (N = 180, 58.6%) at Keio University Hospital and three affiliated hospitals between 1994 and 2017 were enrolled. Oncological outcomes were compared between bladder urothelial carcinoma and upper tract urothelial carcinoma using Cox regression analysis. Results Significantly higher rates of male patients, smokers, neoadjuvant chemotherapy, lymph node involvement and lymphovascular invasion were observed in the bladder urothelial carcinoma group. The incidence of regional lymph node or local recurrence was higher in patients with bladder urothelial carcinoma than in those with upper tract urothelial carcinoma, while that of lung metastasis was lower. In all patients, bladder urothelial carcinoma was independently associated with disease recurrence (hazard ratio (HR) 1.504, P = 0.035) in addition to neoadjuvant chemotherapy and lymphovascular invasion. Bladder urothelial carcinoma was also independently associated with cancer death (HR = 1.998, P = 0.002) as well as lymphovascular invasion. Following the exclusion of patients who received neoadjuvant chemotherapy, bladder urothelial carcinoma remained an independent risk factor for disease recurrence and cancer death (HR = 1.702, P = 0.010 and HR = 1.888, P = 0.013, respectively). Conclusions Bladder urothelial carcinoma may follow worse prognosis compared to upper tract urothelial carcinoma, particularly that with a high pathological stage.

Cyclin‐dependent kinase 12 (CDK12), one of the key factors associated with DNA damage response pathways, is located on chromosome 17 proximal to Erb‐B2 receptor tyrosine kinase 2 (ERBB2). In this report, CDK12 and ERBB2 coamplification was detected by targeted next‐generation sequencing in two urothelial carcinomas. The staining intensity of the CDK12 and human epidermal growth factor receptor‐2 proteins was associated with the prognosis of each urothelial carcinoma case. Our results suggest that CDK12 coamplification with ERBB2 might be associated with tumor aggressiveness and contribution to cancer pathogenesis. Therapies targeting CDK12 should be developed for these patients.

Biochemical recurrence (BCR) after radical prostatectomy (RP) is most commonly diagnosed by detecting an increase in asymptomatic prostate-specific antigen (PSA). We previously reported the “optimal PSA follow-up schedule after RP”. The aim of this study was to confirm the usefulness and safety of that follow-up schedule in another cohort. We retrospectively reviewed the clinicopathological data of 798 consecutive patients who underwent radical prostatectomy between 2009 and 2017. We examined all PSA values measured during follow-up. Furthermore, we estimated the PSA value when we observed the “optimal PSA follow-up schedule” at each timing in the virtual follow-up. BCR was defined as an elevation of PSA to greater than 0.2 ng/ml, and the ideal PSA range for detection of BCR was regarded to be 0.2–0.4 ng/ml. During the mean follow-up period of 5.8 years, BCR occurred in 115 (14.9%) patients and the frequency of virtual follow-up was significantly lower than the actual frequency. However, overlooking of BCR (detecting BCR when PSA exceeded 0.4 ng/ml) was observed in 17 patients, which is higher than the actual frequency of overlooking (12 patients). Therefore, we modified the follow-up schedule, which could achieve the lower follow-up frequency and a limited number of overlooking of BCR (7 patients). This external validation study revealed that the "modified optimal PSA follow-up schedule after RP" can reduce the frequency of PSA measurement with a limited risk of overlooking BCR.

Background Prostate cancer harboring cyclin-dependent kinase 12 (CDK12) abnormalities is a hot topic due to its distinctive clinical features, such as sensitivity to immune checkpoint inhibitors. In the last few years, precision medicine using comprehensive genome sequencing has become familiar, and the era of precision oncology has arrived in the field of prostate cancer. This study aimed to present the demographic characteristics of patients with CDK12 alterations. Methods In 12 patients with detected CDK12 alterations in our hospital between 2015 and 2021, we evaluated their genomic features and clinical course. CDK12 allelic status was classified into three groups: monoallelic loss, potentially biallelic loss, and biallelic loss based on the genome analyses. Results Seven patients already had metastatic cancer at the time of diagnosis, and all 12 patients had Gleason grade ≥ 4. Most cases of biallelic loss or potentially biallelic loss were metastatic cancers at the initial staging, and all these cases were categorized into Gleason grade 5. Two of the 12 patients had BRCA2/RB1 co-loss, and the other two had whole genome duplication. Five patients had a long-term survival of > 6 years, but two patients died within 4 years of diagnosis. Conclusion This is the first Japanese prostate cancer case series with CDK12 alterations. CDK12-altered prostate cancer is a heterogeneous disease, and accumulating cases with detailed information leads to precision oncology.

To stratify the heterogeneity of prostate cancer (PCa) with seminal vesicle invasion (SVI) immunologically after radical prostatectomy (RP) focusing on the tumor microenvironment. We retrospectively reviewed the clinicopathological data of 71 PCa patients with SVI, which is known as a factor of very high risk PCa. Preoperative clinical variables and postoperative pathological variables were evaluated as predictors of BCR with a multivariate logistic regression. Immune cell infiltration including the CD8-positive cell (CD8+ cell) and CD204-positive M2 macrophage (CD204+ cell) was investigated by immunohistochemistry. The cumulative incidence and risk of BCR were assessed with a Kaplan–Meier analysis and competing risks regression. A higher CD8+ cell count in the SVI area significantly indicated a favorable prognosis for cancers with SVI (p = 0.004). A lower CD204+ cell count in the SVI area also significantly indicated a favorable prognosis for cancers with SVI (p = 0.004). Furthermore, the combination of the CD8+ and CD204+ cell infiltration ratio of the SVI area to the main tumor area was a significant factor for BCR in the patients with the PCa with SVI (p = 0.001). In PCa patients with SVI, the combination of CD8+ and CD204+ cell infiltration is useful to predict the prognosis.

INTRODUCTION The goal of partial nephrectomy for renal tumors is complete tumor removal with the preservation of renal function and no complications. Trifecta (total ischemia time

Our aim is to evaluate whether previous non-urothelial malignant history affects the clinical outcomes of patients with non-muscle invasive bladder cancer (NMIBC). We identified 1097 cases treated by transurethral resection of bladder tumors for initially diagnosed NMIBC at our four institutions between 1999 and 2017. We compared clinical characteristics and outcomes between NMIBC patients with and without previous non-urothelial malignant history and investigated whether smoking status and treatment modality for previous cancer affected NMIBC outcomes. A total of 177 patients (16.1%) had previous non-urothelial malignant history (malignant history group). The 5-year recurrence-free survival rate and the 5-year progression-free survival rate in the malignant history group was 46.4% and 88.3%, respectively, which was significantly lower than that in the counterpart (60.2% p = 0.004, and 94.5% p = 0.002, respectively). A multivariate Cox regression analysis identified previous non-urothelial malignant history as an independent risk factor for tumor recurrence (p = 0.001) and stage progression (p = 0.003). In a subgroup of patients who were current smokers (N = 347), previous non-urothelial malignant history was associated with tumor recurrence and stage progression. In contrast, previous non-urothelial malignant history was not associated with tumor recurrence or stage progression in ex-smokers or non-smokers. In a subgroup analysis of NMIBC patients with previous prostate cancer history, those treated with androgen deprivation therapy had a significantly lower bladder tumor recurrence rate than their counterparts (p = 0.027). Previous history of non-urothelial malignancy may lead to worse clinical outcome in patients with NMIBC, particularly current smokers.

Our specific aim was to investigate the prognostic value of effective duration of first androgen deprivation therapy (ADT) and to evaluate the clinical impact on early docetaxel administration with oncological outcomes in castration-resistant prostate cancer (CRPC) patients treated with docetaxel. We identified 148 mCRPC patients who were treated with 75 mg/m2 docetaxel. We defined 16 months as the threshold for the effective duration of ADT, and defined 12 months as the cut-off time for starting docetaxel from the onset of CRPC. Univariate and multivariate analyses were conducted to investigate the prognostic indicators that influenced the survival outcomes. Overall, 81 (54.7%) patients died. The median 1st ADT response was 22.2 months and the median time interval from CRPC onset to docetaxel treatment was 11.7 months. Multivariate analysis indicated that visceral metastasis, bone metastasis extent of disease (EOD) ≥ 2, and effective duration of ADT

INTRODUCTION AND OBJECTIVE:Because CBZ-resistant CRPC has an extremely poor prognosis, establishment of a novel treatment for CBZ-resistant CRPC is greatly needed. The aim of this study was to expl...

INTRODUCTION AND OBJECTIVE:Biochemical recurrence (BCR) after radical prostatectomy (RP) is most commonly diagnosed by detecting an asymptomatic prostate specific antigen (PSA) increase. PSA monito...

Introduction Abiraterone acetate in combination with prednisone is now widely used for the treatment of castration-resistant prostate cancer. Case presentation A 62-year-old patient with a bone metastatic castration-resistant prostate cancer was started on abiraterone acetate at a dose of 1000 mg a day along with 10 mg prednisone. In spite of castrate testosterone level, the laboratory test showed a relatively high level of serum testosterone, which was 21 ng/dL. Within 6 months, the patient achieved a complete prostate-specific antigen response. Follow-up bone scintigraphy demonstrated no area of intense uptake. He had a history of hyperlipidemia and was started on atorvastatin at home just after starting abiraterone acetate. Conclusion This report is a rare case of a clinically complete response to abiraterone acetate in a patient with metastatic castration-resistant prostate cancer.

We analyzed long-term followup data after radical prostatectomy to determine how long we should follow patients in whom the serum prostate specific antigen level measured by an ultrasensitive assay was consistently low.We retrospectively reviewed clinicopathological data for 582 consecutive patients who underwent open or laparoscopic radical prostatectomy between 1995 and 2004, excluding 4 patients who received adjuvant therapy. We stratified the patients according to prostate specific antigen at 3 and 5 years after surgery, and examined subsequent biochemical recurrence (elevation of prostate specific antigen to greater than 0.2 ng/ml) during followup. Mean followup was 9.7 years.At 3 years after surgery prostate specific antigen levels were measured by an ultrasensitive assay in 323 patients who had not experienced biochemical recurrence. In 187 patients with undetectable prostate specific antigen levels (less than 0.01 ng/ml) the 10 and 15-year biochemical recurrence-free survival rates were 99% and 96%, respectively. At 5 years after surgery prostate specific antigen was measured in 315 patients by the ultrasensitive assay. In 162 patients with undetectable prostate specific antigen levels the 10 and 15-year biochemical recurrence-free survival rates were both 100%. In this group the prostate specific antigen level at last followup was less than 0.01 ng/ml in 132 patients, 0.01 to 0.03 ng/ml in 27 patients, and 0.06 ng/ml, 0.07 ng/ml and 0.11 ng/ml in 1 patient each.This long-term review indicates that if patients have continuously undetectable prostate specific antigen levels by an ultrasensitive assay for 5 years, prostate specific antigen monitoring can be stopped with an extremely low risk of subsequent biochemical recurrence.

Background Interstitial pneumonitis is a rare reaction in a previously irradiated area of pulmonary or thoracic lesion after treatment with anticancer drugs such as taxanes. Case presentation A 66-year-old man presented with a fever and dyspnea after treatment with cabazitaxel for castration-resistant prostate cancer. He was treated with an intravenous broad-spectrum antimicrobial agent, however he complained of dyspnea and had a pulse oximetric saturation of 80% while breathing room air. The patients had been treated for bone metastases with 37.5 Gy to the thoracic spine (Th 7) as a local radiotherapy. Radiological images showed pulmonary interstitial opacities in the irradiated field of the both lungs. The steroid pulse therapy was started. The patient’s dyspnea disappeared and the interstitial opacities had also improved. Conclusions This report is a case of interstitial pneumonitis in a castration-resistant prostate cancer patient receiving cabazitaxel after thoracic radiation therapy.

INTRODUCTION AND OBJECTIVES:Intermediate-risk category of non-muscle invasive bladder cancer comprises a very heterogeneous population.METHODS:We reviewed 326 patients with a diagnosis of intermedi...

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INTRODUCTION AND OBJECTIVE:Multiparametric magnetic resonance imaging (mpMRI) has been increasingly used these days and has a role in detecting clinically significant prostate cancer in men with el...

INTRODUCTION Laparoscopic radical nephrectomy is the gold standard for treatment of renal cell carcinoma. However, previous abdominal surgery is generally regarded as a contraindication to the laparoscopic approach because it causes intraperitoneal adhesions, which are thought to interfere with subsequent laparoscopic procedures inside the abdominal cavity. Few studies have examined the influence of prior surgery on laparoscopic nephrectomy. Therefore, the aim of this study was to evaluate the impact of previous laparotomy on laparoscopic nephrectomy. METHODS The records of 251 consecutive patients who had undergone laparoscopic nephrectomy for renal cell carcinoma at our hospital between 2005 and 2015 were reviewed retrospectively. RESULTS Of the 251 laparoscopic nephrectomy patients, 76 patients (30%) had undergone prior abdominal surgery (surgery group), whereas the remaining 175 patients (70%) had not previously had abdominal surgery (control group). There were no significant differences between the control group and the surgery group with regard to pneumoperitoneum time (143 vs 135 min, P = 0.241) or blood loss (39 vs 36 mL, P = 0.763). Next, we divided the patients into two cohorts based on surgeon experience: 98 patients had been treated by an expert (i.e. someone who performs more than 50 laparoscopic procedures per year) and 153 patients had been treated by a non-expert. There was no significant difference in pneumoperitoneum time between the control and surgery groups in each cohort (treated by experts, 108 vs 103 min; treated by non-experts: 162 vs 166 min). CONCLUSION We conclude that laparoscopic nephrectomy may be feasible after previous abdominal surgery and could be one of the surgical options.

We speculated that a heterogeneous population of non-muscle invasive bladder cancer (NMIBC) patients with a previous history of smoking may be more precisely stratified by a biomarker associated with tumor aggressiveness and then focused on the preoperative neutrophil-to-lymphocyte ratio (pre-NLR), which is a simple index of systemic inflammation. Our study population comprised 605 patients initially diagnosed with NMIBC at our 3 institutions between 1995 and 2013. We analyzed the relationships between pre-NLR levels and clinical outcomes in NMIBC. A pre-NLR level of ≥2.2 was defined as elevated according to a calculation by a receiver-operating curve analysis. In overall, a total of 296 patients (48.9 %) had pre-NLR ≥ 2.2, and the pre-NLR level was one of independent risk factors for tumor recurrence and stage progression. Among 344 patients with a previous history of smoking, 184 (53.5 %) had pre-NLR ≥ 2.2 and the pre-NLR level was one of independent risk factors for tumor recurrence and stage progression. The 5-year recurrence-free survival and progression-free survival rates in patients with pre-NLR

INTRODUCTION AND OBJECTIVES: Most patients who fail treatment for prostate cancer do so early, and these patients should therefore be followed up more closely during the first years after radical prostatectomy. Most often, for monitoring of cancer recurrence, serum prostate specific antigen (PSA) is obtained at threeto sixmonth intervals for the first three years, and annually thereafter. However, tumor or patient characteristics may allow alterations to this schedule. In this study, we analyzed our long-term follow-up data after radical prostatectomy, and determined how long we should follow the patients whose PSA level continuously remains low. METHODS: We retrospectively reviewed clinicopathological data in 582 consecutive patients who underwent radical prostatectomy between 1995 and 2004, excluding 4 patients who received adjuvant therapy. We stratified the patients according to their PSA levels at 3 and 5 years after surgery, and examined subsequent biochemical recurrence. Biochemical recurrence was defined as the elevation of PSA to above 0.2 ng/mL. The mean follow-up interval was 9.7 years. RESULTS: At 3 years after surgery, PSA levels were measured by ultra-sensitive assay in 323 patients who did not experience biochemical recurrence at that time, and we divided them into 4 groups according to their PSA levels (PSA

Purpose Patients with intermediate-risk non–muscle-invasive bladder cancer have traditionally been defined as those not included in the low- or high-risk groups. Therefore, the intermediate-risk group consists of heterogeneous patients. Materials and methods We reviewed 326 patients diagnosed with intermediate-risk tumors. We subclassified these patients into 3 groups according to their clinical courses. Group A included patients with initial and multiple low-grade tumors (N = 170). Group B consisted of patients with a low-grade tumor that recurred after a low-risk tumor (N = 97), and Group C consisted of patients with a low-grade tumor that recurred after a high-risk tumor (N = 59). Results The 2-year recurrence-free survival rate was significantly lower in Group C (42%) than in Groups A (69%, P

To the Editor, Enzalutamide is approved by FDA for the treatment of castration-resistant prostate cancer (CRPC) [1]. Common adverse events include fatigue, diarrhea, and hot flashes [1]. However, s...