金尾 健人

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.

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.

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.

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.

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.

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.

© 2014, Society of Surgical Oncology. Background: To externally validate the prognostic impact of preoperative neutrophil–lymphocyte ratio (pre-NLR) in patients with upper tract urothelial carcinoma (UTUC) following radical nephroureterectomy (RNU).Methods: A total of 665 patients from 12 institutions were included. The median follow-up was 28 months. Associations between pre-NLR level and outcome were assessed using multivariate analysis. A pre-NLR level of >3.0 was defined as elevated.Results: Pre-NLR levels were elevated in 184 patients (27.7 %), and pre-NLR elevation was significantly associated with worse pathological features such as tumor grade 3, advanced pT stage, positive lymphovascular invasion (LVI), and lymph node involvement in RNU specimens. The 5-year recurrence-free and cancer-specific survival rates were 57.0 % (p < 0.001) and 60.2 % (p < 0.001), respectively, in patients with elevated pre-NLR, and 69.2 and 77.3 %, respectively, in their counterparts. Multivariate analysis showed that elevated pre-NLR was an independent risk factor for predicting subsequent disease recurrence (p = 0.037; hazard ratio (HR) 1.38) and cancer-specific mortality (p = 0.036;, HR 1.47), although the addition of pre-NLR slightly improved the accuracies of the base model for predicting both disease recurrence and cancer-specific mortality to 79.8 % (p = 0.041) and 83.0 % (p = 0.039), respectively (gain in predictive accuracy: 0.2 and 0.1 %, respectively).Conclusion: This multi-institutional study revealed that elevated pre-NLR was significantly associated with worse pathological features such as tumor grade 3, advanced pT stage, positive LVI, and lymph node involvement in RNU specimens, and elevated pre-NLR was an independent risk factor of disease recurrence and cancer-specific mortality in UTUC patients treated with RNU.

This report documents that the case of 24-year-old male with a non-palpable testicular tumor that contained non-seminomatous germ cell components detected by US.