Kent KANAO

Abstract Background Deep-learning models for prostate cancer detection often require large datasets, which can be challenging to obtain and may lead to domain shift issues in various clinical settings. Purpose This study aimed to develop a deep-learning model for prostate cancer detection on magnetic resonance images using few-shot learning and compare its performance with radiologists. Materials and Methods This retrospective study used 99 cases (80 positive, 19 negative) of confirmed prostate cancer, diagnosed through needle biopsy from 2017 to 2022, with 20 cases for training, 5 for validation, and 74 for testing. The 2D transformer model was trained on T2-weighted, diffusion-weighted, and apparent diffusion coefficient map images. Model predictions were compared between the two radiologists using the Matthews correlation coefficient (MCC) and F1 score, and the bootstrap method was used to calculate 95% confidence intervals (CIs). Results Seventy-four patients (mean age, 71 years ± 8; 60 men) were included in the test set. The model achieved an MCC of 0.297 (95% CI: 0.095–0.474) and F1 score of 0.707 (95% CI: 0.598–0.847). Radiologist 1 had an MCC of 0.276 (95% CI: 0.054–0.484) and an F1 score of 0.741 (95% CI: 0.632–0.832), while Radiologist 2 had an MCC of 0.504 (95% CI: 0.289–0.703) and an F1 score of 0.871 (95% CI: 0.800–0.931). The performance of the model was not significantly different from that of Radiologist 1 (MCC difference: 0.021, 95% CI: −0.270–0.306; F1 score difference: −0.034, 95% CI: −0.153–0.078), but was lower than that of Radiologist 2 (F1 difference: −0.16, 95% CI: −0.287– - 0.061). Conclusion A deep-learning model trained on only 20 cases achieved a performance comparable to one radiologist in detecting prostate cancer on magnetic resonance images, demonstrating the potential of few-shot learning in addressing domain shift challenges. Key Results A deep learning model for prostate cancer detection on MRI was developed using only 20 training cases. The model achieved performance comparable to one radiologist (MCC: 0.297 vs 0.276) but lower than another (F1: 0.707 vs 0.871). Few-shot learning demonstrated potential for addressing domain shift challenges in medical imaging AI. Summary Statement Few-shot learning enables development of prostate cancer detection models on MRI with performance comparable to radiologists, using minimal training data.

BACKGROUND: In Japan, the authorized period (2-4 h) between oral administration of 5-aminolevulinic acid hydrochloride (5-ALA) and transurethral resection for non-muscle invasive bladder cancer (NMIBC) may restrict photodynamic diagnosis (PDD) usage. Therefore, this prospective, single-arm, phase III study aimed to evaluate the diagnostic accuracy and safety of PDD at an extended administration period (4-8 h). METHODS: From January 2022 to May 2023, 161 patients with NMIBC were enrolled from eight hospitals. The primary endpoint was the blue light (BL) sensitivity of pathologically positive biopsies. The secondary endpoints were a comparison of the specificity and positive and negative prediction rates under BL and white light (WL) conditions. RESULTS: A total of 1242 specimens comprising 337 histological NMIBC specimens were analyzed. BL-sensitivity was 95.3%. Its lower limit of 95% confidence interval (92.4-97.3%) exceeded the threshold (70%) of non-inferiority to authorized usage. Sensitivity and specificity were significantly higher and lower for BL than those for WL (95.3% vs. 61.1%, P < 0.001; 52.7% vs. 95.2%, P < 0.001), respectively. The positive and negative predictive rates were significantly lower and higher for BL than those for WL (42.9% vs. 82.7%, P < 0.001; 96.8% vs. 86.8%, P < 0.001), respectively. Of the 145 patients receiving 5-ALA, 136 (93.8%) and 75 (51.7%) experienced 377 adverse events and 95 adverse reactions, respectively, most of which were grade 1 or 2. CONCLUSION: For extended period, the efficacy of PDD for NMIBC was similar to that of authorized period, in terms of higher sensitivity and lower specificity compared with WL, and the safety was acceptable.

UNLABELLED: A 71-year-old man with bone metastasis of hormone-sensitive prostate cancer was treated with androgen deprivation therapy and apalutamide. Radium-223 and radiation therapy were administered after it become castration resistant. Although prostate-specific antigen levels remained low, multiple subcutaneous metastases of neuroendocrine prostate cancer were observed. A review of the pre-treatment prostate needle biopsy revealed a small component with features suggestive of neuroendocrine differentiation. Phosphatase and tensine homolog loss and tumor protein p53 overexpression were observed, confirming the diagnosis of aggressive variant prostate cancer. Platinum-based chemotherapy was administered; however, the patient died 28 months after diagnosis. In this case, if the diagnosis of aggressive variant prostate cancer had been made at an earlier time by biopsy specimens, there might have been a possibility to improve the prognosis by the earlier introduction of the platinum-based regimen. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13691-024-00673-7.

Choroidal metastasis originating from renal cell carcinomas (RCCs) is rare. To the best of our knowledge, 31 cases of choroidal metastasis from RCC have been reported in the English literature as of January 31, 2024. Nevertheless, physicians need to be vigilant in recognizing this condition, as its progression impacts the quality of life (QOL) of affected patients. In Case 1, a 60-year-old male with a medical history of papillary RCC experienced a deterioration in visual acuity (VA) and was diagnosed with solitary choroidal metastasis. Subsequently, multiple metastases were identified, prompting the initiation of a combination therapy regimen consisting of pembrolizumab plus axitinib. Despite treatment, progression of choroidal metastasis and a further decline in VA were observed. The patient underwent stereotactic radiotherapy and experienced complete resolution of the choroidal metastasis, accompanied by a slight improvement in VA. In Case 2, a 76-year-old man presented with a renal tumor accompanied by lung metastases. He underwent nephrectomy, and the histological diagnosis was papillary RCC. We initiated combination therapy consisting of nivolumab plus cabozantinib. The patient experienced a decrease in VA during treatment. We identified extensive fine metastases scattered throughout the bilateral choroid. We administered axitinib, but the patient experienced bilateral blindness. Given the absence of established therapy for choroidal metastasis, it is crucial to maintain flexibility in treatment selection. Local or systemic approaches should be used as deemed appropriate for each individual case.

OBJECTIVES: We aim to evaluate the risk of recurrence after neoadjuvant chemotherapy followed by radical cystectomy, particularly in ypT2 disease in patients with urothelial carcinoma, because it is not clear if all eligible patients with high-risk muscle-invasive urothelial carcinoma should be treated with adjuvant nivolumab. MATERIALS AND METHODS: We analysed the radiological and clinicopathological features, including cT and ypT stages, of 197 patients who had undergone two to four cycles of cisplatin-based neoadjuvant chemotherapy and radical cystectomy without adjuvant chemotherapy. We stratified the risk of postoperative recurrence by these factors. RESULTS: The median observation period was 29.6 (interquartile range, 11.4-71.7) months, and disease recurrence was observed in 58 patients. Multivariate analysis revealed that ypT stage (P = 0.019) and lymphovascular invasion (P = 0.015) were independent risk factors for postoperative recurrence. The ypT2 group (n = 38) had significantly better recurrence-free survival than the ypT3 group (n = 41) (median recurrence-free survival: not reached vs. 13.4 months, respectively, P = 0.005). In ypT2 disease, the cT2 and ypT2 group (n = 15), which was diagnosed as cT2 preoperatively and then diagnosed as ypT2 postoperatively, had significantly better recurrence-free survival than the cT3/4 and ypT2 group (n = 23) (median recurrence-free survival: not reached vs. 63.1 months, respectively, P = 0.034). There was no significant difference in recurrence-free survival between the ypT ≤ 1 (n = 106) and the cT2 and ypT2 groups (median recurrence-free survival: not reached in both, P = 0.962). CONCLUSION: Patients with cT2 and ypT2 stage have a relatively low risk of recurrence and thus have a lower need for adjuvant nivolumab, particularly those with ypT2.

UNLABELLED: In advanced urothelial carcinoma (UC), approximately 20% of patients respond to pembrolizumab, an anti-programmed cell death-1 (PD-1) antibody. Herein, we reported a single case of UC showing coexistence of sarcomatoid subtype and glandular differentiation. Notably, only glandular differentiation was recurrent, probably progressive, and metastatic, which showed complete response to pembrolizumab. An 80-year-old woman presented with hematuria and dysuria, and an intra-vesical tumor was detected on ultrasound. Transurethral resections (TUR) were performed three times. In the first TUR, a sub-pedunculated tumor and a flat lesion were closely but independently located. Pathologically, the sub-pedunculated tumor was an invasive UC, sarcomatoid subtype. Meanwhile, the flat lesion was invasive UC with glandular differentiation. Despite the second and the additional TUR, the tumor was growing and a lymph node metastasis was detected. The third TUR specimen showed UC with glandular differentiation, and a positive PD-L1 expression as well as high density CD8-positive lymphocytic cells infiltration were observed. Pembrolizumab was administered for four courses after terminating the chemotherapy. The CT scan revealed shrinkage of both primary tumor and metastases. Cystectomy and lymph nodes dissection were performed, and no residual carcinoma was detected. The therapeutic effect was regarded as pathological complete response. Pembrolizumab could be effective for special subtype or divergent differentiation of UC, particularly in an event of an 'immune hot' tumor. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13691-022-00568-5.

BACKGROUND/AIM: CheckMate 214 study revealed that nivolumab plus ipilimumab combination therapy showed a strong and durable effect compared to sunitinib for patients with advanced renal cell carcinoma (aRCC). Most of the patients underwent previous nephrectomy before systemic treatment. We retrospectively investigated the clinical outcomes of Japanese patients treated with cytoreductive nephrectomy following nivolumab plus ipilimumab for aRCC. PATIENTS AND METHODS: Seventy-nine patients were treated with systemic therapy for aRCC between October 2018 and August 2021 at the Saitama Medical University International Medical Center. Ten of 61 patients treated with nivolumab plus ipilimumab underwent cytoreductive nephrectomy after the combined immunotherapy. RESULTS: The median overall survival and progression-free survival were 24.3 and 15.9 months, respectively. The objective response rate was 50.8%; 9.8% of patients had a complete response, and the median time to objective response was 3.2 (range=1.3-19.7) months. The estimated percentage of patients who sustained an objective response at 30 months was 73.0%. Twenty-three patients (74%) in the complete or partial response (CR/PR) group, 11 patients (52%) in the stable disease (SD) group, and two patients (22%) in the progressive disease (PD) group had immune-related adverse events of grade 3 or higher, respectively. For all 10 patients, cytoreductive nephrectomy following nivolumab plus ipilimumab treatment were completed safely. Three patients achieved a pathological complete response without viable cancer cells. Only two patients had residual lesions on images after deferred cytoreductive nephrectomy; the remaining patients achieved radiological CR. CONCLUSION: Cytoreductive nephrectomy after nivolumab plus ipilimumab treatment could be useful in a limited number of cases, possibly resulting in curative nephrectomy due to the durable therapeutic effect of immunotherapy.

Introduction: Our patient treated with pembrolizumab and axitinib is one of the longest survivors in Japan on KEYNOTE 426, despite adverse events, including delayed-onset hepatitis. We herein present a detailed clinical course and short discussion on the case. Case presentation: This was a 49-year-old male with clear cell renal cell carcinoma and lung metastases. After cytoreductive nephrectomy, treatment with pembrolizumab plus axitinib was initiated and the patient demonstrated a radiographic partial response as best response. The main adverse event was pembrolizumab-induced delayed-onset hepatitis, which was successfully treated with prednisolone. Pembrolizumab was re-initiated and completed. Conclusion: The survival benefit in the present case may be due to the initial potent anti-cancer effects of axitinib and durable immune effects of pembrolizumab, leading to long-term treatment-free survival.

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

An 80 year old Japanese man with bilateral ureteral cancer underwent laparoscopic bilateral nephroureterectomy and lymph-node dissection. The pathological stage of the left and right ureteral tumors was pT3pN0M0. He received two courses of adjuvant gemcitabine and cisplatin chemotherapy while undergoing hemodialysis. The standard dose of gemcitabine and 50% of the standard dose of cisplatin were administered on the same day. Hemodialysis was started 6 h after gemcitabine administration and 1 h after cisplatin administration. The side effects were evaluated according to the Common Terminology Criteria for Adverse Events v4.0. In the first course, Grade 4 side effects including leukopenia, neutropenia, and thrombocytopenia were observed. He was treated with granulocyte colony-stimulating factor and platelet transfusion. Because the second course was administered without reducing the doses, granulocyte colony-stimulating factor was administered prophylactically, and Grade 4 side effects were reduced to Grade 3. Gemcitabine plus cisplatin chemotherapy can be administered safely in a patient with advanced ureteral cancer undergoing hemodialysis by adequately managing adverse events.

INTRODUCTION: To describe laparoendoscopic single-site simple nephrectomy and reduced port simple nephrectomy for inflammatory nonfunctioning kidney. CASE PRESENTATION: Case 1: a 58-year-old female with fever was referred to our hospital. Computed tomography demonstrated a markedly atrophic right kidney and mild hydronephrosis. Case 2: a 64-year-old male with a history of several intra-abdominal surgeries visited our hospital with a complaint of left back pain and fever. Computed tomography demonstrated left marked hydronephrosis, thinning of renal parenchyma, and duplicated inferior vena cava. After antibiotic treatment, transperitoneal reduced port simple nephrectomy and retroperitoneal laparoendoscopic single-site simple nephrectomy were performed in Case 1 and 2, respectively, because the function of the affected kidney was almost lost on renography. Although adhesion was slightly noted around the renal hilum in Case 1, neither conversion to laparotomy nor placement of additional ports was needed. CONCLUSION: Laparoendoscopic single-site simple nephrectomy and reduced port simple nephrectomy for inflammatory nonfunctioning kidney may be options for experienced laparoscopic surgeons.

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

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

Reduced port laparoscopic radical nephrectomy (RPLRN) is an equivalent approach to conventional laparoscopic radical nephrectomy (LRN). In LRN, one wound generally needs to be extended for specimen extraction; therefore, some ingenuity is needed to achieve a good cosmetic outcome. We herein describe our initial experience of RPLRN using an umbilical zigzag skin incision for renal cell carcinoma (RCC). A 64-year-old female [body mass index (BMI): 20.0 kg/m2] was diagnosed with right RCC, which was 35 mm in diameter (clinical T1aN0M0). Case 2: a 68-year-old male (BMI: 23.2 kg/m2) was diagnosed with right RCC, which was 58 mm in diameter (clinical T1bN0M1), and perinephric fat was relatively thick. The procedure was safely completed in both cases. Total operative times, pneumoperitoneal times, and estimated blood loss in Case 1 and 2 were 90 and 145 min, 49 and 90 min, and 5 and 80 ml, respectively, and the times required to construct umbilical ports and close umbilical wounds were 8 and 9 min and 33 and 46 min, respectively. In Case 1, the specimen was easily extracted without the extension of the umbilical skin incision, whereas it was extended by an additional 2 cm in Case 2. The umbilical wound was inconspicuous in both cases. RPLRN using an umbilical zigzag skin incision for RCC was safely performed without complications, and clashing between instruments was minimized. The high level of cosmesis is advantageous and an umbilical zigzag skin incision may contribute to more widespread use of RPLRN for RCC; however, further studies on long-term oncological outcomes are needed.

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

Castration-resistant prostate cancer (CRPC) patients with liver metastases have an extremely poor prognosis. Herein, we report a rare patient who achieved a complete response by docetaxel chemotherapy for this aggressive disease. A 67-year-old Japanese male diagnosed with local prostate cancer [initial prostate specific antigen (PSA) of 10.3 ng/mL, a highest Gleason score of eight] received radical prostatectomy (RP) followed by salvage radiotherapy for PSA recurrence without distant metastases. After four years, androgen deprivation therapy was commenced for both local recurrence and elevated PSA. After a further four years, despite good control of PSA (1.2 ng/mL), other clinical findings including radiographic images revealed CRPC with multiple liver metastases. Ten cycles of docetaxel chemotherapy achieved a complete response for more than five years. In conclusion, even if a patient has CRPC with liver metastases, early diagnostic imaging irrespective of the PSA level may provide a better response to early docetaxel chemotherapy.

Flomoxef is used to treat bacterial prostatitis; however, its prostatic pharmacokinetics have not been fully clarified. Flomoxef (500 or 1000 mg) was administered to patients with benign prostatic hypertrophy (n = 54). After a 0.5-h infusion, venous blood samples were drawn at time points of 0.5-5 h, and prostate tissue samples were collected at time points of 0.5-1.5 h during transurethral resection of the prostate. The drug concentrations in plasma and prostate tissue were analyzed pharmacokinetically and used for a stochastic simulation to predict the probability of attaining pharmacodynamic target in prostate tissue. Showing dose linearity in the prostatic pharmacokinetics, flomoxef rapidly penetrated into prostate tissue, with a prostate/plasma ratio of 0.48-0.50 (maximum drug concentration) and 0.42-0.55 (area under the drug concentration-time curve). Against the tested populations of Escherichia coli, Klebsiella and Proteus species isolates, 0.5-h infusion of 1000 mg three times daily achieved a ≥90% expected probability of attaining the bactericidal target (70% of the time above the minimum inhibitory concentration [MIC]) in prostate tissue. The site-specific pharmacodynamic-based breakpoint (the highest MIC at which the target-attainment probability in prostate tissue was >90%) values were 0.25 mg/L (MIC for 90th percentile of E. coli and Klebsiella species) for 500 mg four times daily and 0.5 mg/L (MIC90 of Proteus species) for 1000 mg four times daily. These results help to fully characterize the prostatic pharmacokinetics of flomoxef, while also helping to rationalize and optimize the dosing regimens for prostatitis based on site-specific pharmacodynamic target attainment.

BACKGROUND/AIM: Patients with metastatic renal cell carcinoma (RCC) with cardiac metastasis have had poor outcomes in the era of molecular targeted therapy. There are few reported outcomes for patients with cardiac metastasis of RCC treated with immune checkpoint inhibitors (ICIs). CASE REPORT: A 32-year-old female presented with metastatic RCC (unclassified type) with contralateral renal and cardiac metastases, as well as renal hilar lymph node metastases (cT4N2M1). An 18F-fluorodeoxyglucose (FDG) positron-emission tomography (PET) computed tomographic (CT) scan was useful in diagnosing cardiac metastasis. Nivolumab plus ipilimumab achieved prominent shrinkage of almost all tumors except for one cardiac tumor. FDG-PET/CT scan also revealed the marked attenuation of FDG uptake in each tumor. In addition, a needle biopsy of the remaining primary renal tumor was pathologically observed to have no viable cancer cells. CONCLUSION: This successful case suggests that ICIs might provide a better outcome even for patients with cardiac metastasis of RCC, and that FDG-PET/CT scan might be useful for therapeutic assessment, as well as diagnosis.

Background: Recently, two techniques of robot-assisted radical prostatectomy (RARP), which preserve dorsal vein complex (DVC), endopelvic fascia, and full neurovascular bundle (NVB), through anterior approach were reported. The techniques in a relatively large workspace seem less technically demanding than Retzius-sparing RARP. In this case report, we present a further modified technique of transperitoneal-anterior-antegrade approach with a division of the endopelvic fascia to reduce the technical demands. Case Presentation: In a routine evaluation, a 65-year-old man was shown to have a prostate-specific antigen level of 5.07 ng/mL. Prostatic biopsy revealed a Gleason score of 6 (3 + 3) adenocarcinoma in 2 of the 12 specimens, and the clinical stage was diagnosed as cT2aN0M0. RARP was performed including transperitoneal full NVB sparing, antegrade preservation of DVC, and division of endopelvic fascia to increase the prostate mobility and reduce technical demands. The patient completely gained continence on the day after removal of the catheter, and potency was recovered 30 days after surgery. Conclusion: Our DVC preservation technique in the transperitoneal-anterior-antegrade approach with a division of the endopelvic fascia during RARP may be safe, reduce technical demands, and facilitate early recovery of continence and sexual function after surgery.

BACKGROUND: The objective of this study was to categorize prostate-specific antigen (PSA) response during cabazitaxel therapy in patients with metastatic castration-resistant prostate cancer (mCRPC) into different patterns and to investigate the prognostic impact of the PSA response patterns. METHODS: We reviewed data from patients with mCRPC who had been treated with cabazitaxel therapy at four institutions belonging to Tokai Urologic Oncology Research Seminar. Patients eligible for this study had received at least three cycles of cabazitaxel treatment at three- or four-week intervals. The PSA response patterns were categorized as primary resistance (PR), response (RE), stabilization (ST), and fluctuating (FL). The overall survival (OS) was compared among the patterns. RESULTS: Data from a total of 50 patients were analyzed in this study. The number of patients exhibiting PR, RE, ST and FL patterns were 18 (36%), 14 (28%), 12 (24%) and 6 (12%), respectively. The median (95% CI) OS of patients with PR and RE patterns was 10.7 (5.6-15.9) and 14.9 (6.8-23.0) months, respectively, and was not reached for patients with ST and FL patterns. The OS of patients with the FL pattern was significantly better than that of patients with PR (P = 0.012) and RE (P = 0.010) patterns. CONCLUSION: There were some patients whose PSA were fluctuating during cabazitaxel therapy in patients with mCRPC. Because the prognosis of such patients was relatively good, the judgment to discontinue the cabazitaxel therapy after PSA rise followed by decrease should be made prudently.

INTRODUCTION: Transurethral resection of bladder tumor is widely used in combination with photodynamic diagnosis to treat non-muscle invasive bladder cancer. We experienced an intriguing case, in which bladder cancer infiltrated into the right ureteral orifice and was resected via photodynamic diagnosis-assisted transurethral resection involving the oral administration of 5-aminolevulinic acid. CASE PRESENTATION: This case was a 71-year-old Japanese man. He was diagnosed with bladder carcinoma, which had infiltrated into the right ureter (clinical classification: T1, N0, M0). He underwent transurethral resection involving the oral administration of 5-aminolevulinic acid. We successfully resected the tumor in the ureteral orifice, which was accomplished by resecting the ureteral orifice until the non-luminescent lumen was exposed. After the surgery, to prevent recurrence, Bacillus Calmette-Guérin was administered intravesically after right ureteral stent placement. CONCLUSION: Photodynamic diagnosis-assisted transurethral resection involving the oral administration of 5-aminolevulinic acid has the potential to treat ureteral tumors derived from bladder tumors.

BACKGROUND: Regulatory T cells (Tregs) play important roles in the suppression of immune responses, including antitumor immune responses. C-C chemokine receptor 4 (CCR4) is highly expressed on effector Tregs, and anti-CCR4 antibody is attracting attention as a novel immunotherapeutic agent for solid tumors. This study aimed to evaluate the expression of CCR4-positive Tregs (CCR4+Tregs) in prostate cancer and estimate the clinical potential of CCR4-targeting therapy for prostate cancer. METHODS: A total of 15 radical prostatectomy (RP) specimens and 60 biopsy specimens from individuals diagnosed with prostate cancer were analyzed to evaluate the infiltration of CCR4+Tregs in prostate cancer. The relationships between the number of CCR4+Tregs and clinical parameters were investigated in RP and biopsy specimens. Moreover, the total number of Tregs, CCR4+Tregs, and T cells and the ratio of CCR4+Tregs to Tregs and T cells in biopsy specimens were compared between patients with poor prognosis who progressed to castration-resistant prostate cancer (CRPC) within 12 months (n = 13) and those with good prognosis who were stable with hormone-sensitive prostate cancer over 12 months (n = 47). Furthermore, biopsy specimens were divided into two groups: low and high CCR4+Treg expression groups and the prognosis was compared between them. RESULTS: There was a higher expression of CCR4+Tregs in RP specimens with a higher (≥8) Gleason score than in those with a lower (<8) Gleason score (P = .041). In biopsy specimens, 65.9% Tregs were positive for CCR4. The number of CCR4+Tregs positively correlated with clinical stage (P < .001) and Gleason score (P = .006). The total number of Tregs and CCR4+Tregs significantly increased in the poor prognosis group compared with that in the good prognosis group (P = .024 and .01, respectively). Furthermore, patients with lower CCR4+Treg expression levels showed a significantly longer time to progression to CRPC (not reached vs 27.3 months; P < .001) and median survival time (not reached vs 69.0 months; P = .014) than those with higher expression levels. CONCLUSIONS: CCR4+Tregs are highly infiltrated in the prostate tissue of patients with poor prognosis with potential to progress to CRPC. Furthermore, the degree of infiltration of CCR4+Tregs is related to the prognosis of prostate cancer.

Docetaxel (DOC) is one of the most effective chemotherapeutic agents against castration‑resistant prostate cancer (CRPC). Despite an impressive initial clinical response, the majority of patients eventually develop resistance to DOC. In tumor metabolism, where tumors preferentially utilize anaerobic metabolism, lactate dehydrogenase (LDH) serves an important role. LDH controls the conversion of pyruvate to lactate, with LDH‑A, one of the predominant isoforms of LDH, controlling this metabolic process. In the present study, the role of LDH‑A in drug resistance of human prostate cancer (PC) was examined by analyzing 4 PC cell lines, including castration‑providing strains PC3, DU145, LNCaP and LN‑CSS (which is a hormone refractory cell line established from LNCaP). Sodium oxamate (SO) was used as a specific LDH‑A inhibitor. Changes in the expression level of LDH‑A were analyzed by western blotting. Cell growth and survival were evaluated with a WST‑1 assay. Cell cycle progression and apoptotic inducibility were evaluated by flow cytometry using propidium iodide and Annexin V staining. LDH expression was strongly associated with DOC sensitivity in PC cells. SO inhibited growth of PC cells, which was considered to be caused by the inhibition of LDH‑A expression. Synergistic cytotoxicity was observed by combining DOC and SO in LN‑CSS cells, but not in LNCaP cells. This combination treatment induced additive cytotoxic effects in PC‑3 and DU145 cells, caused cell cycle arrest in G2‑M phase and increased the number of cells in the sub‑G1 phase of cell cycle in LN‑CSS cells. SO promoted DOC induced apoptosis in LN‑CSS cells, which was partially caused by the inhibition of DOC‑induced increase in LDH‑A expression. The results strongly indicated that LDH‑A serves an important role in DOC resistance in advanced PC cells and inhibition of LDH‑A expression promotes susceptibility to DOC, particularly in CRPC cells. The present study may provide valuable information for developing targeted therapies for CRPC in the future.

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

A 61-year-old woman with metastatic renal carcinoma was treated with axitinib as a second-line tyrosine kinase inhibitor. Thirteen days after the treatment, the patient developed reversible posterior leukoencephalopathy syndrome (RPLS). Her symptoms and imaging findings resolved after withdrawal of axitinib, blood pressure control, and administration of glycerin and levetiracetam. RPLS should be kept in mind as a possible rare adverse event after axitinib administration.

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

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

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

PURPOSE: Current guidelines do not yet provide any recommendations for adjuvant chemotherapy in patients with upper tract urothelial carcinoma managed with radical nephroureterectomy. We evaluated whether an adjuvant chemotherapeutic regimen would affect the clinical outcome in patients with high risk upper tract urothelial carcinoma. MATERIALS AND METHODS: We identified 873 patients who had undergone radical nephrouretectomy for localized upper tract urothelial carcinoma at 14 Japanese institutions between 1993 and 2011. We assessed whether the type of regimen, such as methotrexate, vinblastine, doxorubicin and cisplatin, and gemcitabine and cisplatin, in an adjuvant setting, could affect the subsequent clinical outcome of patients with upper tract urothelial carcinoma. RESULTS: On multivariate analysis pathological T stage, tumor grade, lymphovascular invasion and lymph node involvement were prognostic factors for recurrence-free survival and cancer specific survival. We defined 229 patients with 3 or more of these factors as the high risk group. In an analysis according to adjuvant regimen, Kaplan-Meier curves showed that the 1 and 2-year recurrence-free survival rates in the methotrexate, vinblastine, doxorubicin and cisplatin treated group were 71.4% and 47.9%, which were significantly higher than in the gemcitabine and cisplatin treated group (48.2% and not reached, p=0.022) or those not treated with adjuvant chemotherapy (53.4% and 39.6%, p=0.039). Similar results were observed in terms of cancer specific survival. CONCLUSIONS: Our study showed that pT3-4, tumor grade 3, positive lymphovascular invasion and lymph node involvement were independent risk factors for disease mortality in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy. In the high risk group methotrexate, vinblastine, doxorubicin and cisplatin adjuvant chemotherapy contributed to improve subsequent mortality compared to gemcitabine and cisplatin or no adjuvant chemotherapy.

OBJECTIVE: To individualize prostate-specific antigen threshold values to avoid overdiagnosis of prostate cancer and reduce unnecessary biopsy in elderly men. METHODS: A total of 406 men aged over 70 years old with prostate-specific antigen levels between 4.0 and 20.0 ng/ml, normal digital rectal examination results and diagnosed by transrectal needle biopsy were retrospectively analyzed. The patients were divided into a no/favorable-risk cancer group or an unfavorable-risk cancer group based on their Gleason score and the number of positive cores. Prostate-specific antigen levels, percent free prostate-specific antigen level, prostate transition zone volume and the number of previous biopsies were used to discriminate between the two groups. The optimal individualized prostate-specific antigen threshold values based on the other variables that gave a sensitivity of 95% for the detection of unfavorable-risk cancer were calculated using a boosting method for maximizing the area under the receiver operating characteristic curve. RESULTS: A total of 66 men had favorable-risk cancer, and 139 had unfavorable-risk cancer. The area under the receiver operating characteristic curve of the combination model determined by the boosting method for maximizing the area under the receiver operating characteristic curve was 0.852. The sensitivity and specificity of the threshold values for the detection of unfavorable-risk cancer were 95 and 36%, respectively. By using the threshold values, 100 (25%) of the subjects with no/favorable-risk cancer could have avoided undergoing biopsies, with a <5% risk of missing the detection of unfavorable-risk cancer. CONCLUSIONS: These individualized prostate-specific antigen threshold values may be useful for determining an indication of prostate biopsy for elderly men to avoid overdiagnosis of prostate cancer and reduce unnecessary biopsy.

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

PURPOSE: To investigate the site-specific pattern of disease recurrence and/or metastasis and the associated patient outcomes after radical nephroureterectomy (RNU) in upper tract urothelial carcinoma (UTUC). METHODS: A total of 733 patients with UTUC from a retrospective multi-institutional cohort were included, with a median follow-up of 34 months. Associated patient outcomes were analyzed by multivariate analysis. To evaluate the influence of primary tumor location, we divided it into four areas: renal pelvis, and upper, middle, and lower ureter. RESULTS: A total of 218 patients experienced disease recurrence, with the majority of relapses occurring within the first 3 years. Cumulative incidence rates of first disease recurrence at 1 and 3 years were 18.9 and 29.8 %, respectively. Of these patients, 38.5 % developed distant recurrence; 17.4 % experienced both local and distant recurrences; and 44.0 % developed isolated local recurrence. The predominant sites of distant metastasis were lung, liver, and bone. Multivariate analysis revealed that the prevalence of local recurrence and lung metastasis was significantly associated, with primary tumor location being independent of other clinicopathological variables. Lower/middle ureter tumors had a higher rate of local recurrence in the pelvic cavity, and renal pelvic tumors had a higher prevalence of distant relapse in the lungs. Similar results were obtained when rerunning the data set by excluding patients who received adjuvant chemotherapy (n = 131). CONCLUSIONS: This multi-institutional study provided a detailed picture of metastatic behavior after RNU, and primary tumor locations were associated with unique patterns of metastatic spread in UTUC patients.