大島 将

BACKGROUND: Robot-assisted radical prostatectomy (RARP) is a preferred minimally invasive surgical treatment for prostate cancer. The number of elderly patients and those with cardiovascular and/or cerebrovascular issues undergoing surgery is increasing, and many of them are taking antithrombotic (AT) agents. However, the effect of AT agents on postoperative urinary recovery has not been adequately studied. In this study, we analyzed the differences in the postoperative recovery of urinary continence and oncological outcomes in patients undergoing RARP for localized prostate cancer between AT agent adherents and non-adherents. METHODS: A total of 394 patients who underwent conventional anterior RARP between February 2015 and February 2021 were categorized into two groups: those taking oral AT agents (AT group) and the control group. Urinary continence recovery, complications, and oncological outcomes were compared between the groups. A Cox proportional hazards analysis was performed to identify clinical factors that affect urinary continence recovery. RESULTS: The background data and bleeding complications did not differ significantly between the groups. The recovery of continence was significantly poorer in the AT group in terms of complete pad free (HR: 0.53 [95% CI: 0.39-0.71]) and use of ≤ 1 safety pad (HR: 0.74 [95% CI: 0.59-0.94]). The rate of anastomotic leakage on cystography was significantly higher in the AT group (20.9% vs. 6.7%). A univariate analysis revealed that taking antithrombotic agents, higher prostate-specific antigen levels, and a more advanced clinical stage were associated with a poor urinary continence recovery; a multivariate analysis showed that taking AT agents was an independent factor negatively associated with urinary continence recovery. There was no significant difference between the groups in the positive surgical margin rate (19.0% vs. 23.8%) or the biochemical-recurrence-free rate. CONCLUSION: Taking oral AT agents may be associated with poor urinary continence recovery after RARP.

Prostate cancer is an androgen-dependent malignancy that presents a marked treatment challenge, particularly after progression to the castration-resistant stage. Traditional treatments such as androgen deprivation therapy often lead to resistance, necessitating novel therapeutic approaches. Previous studies have indicated that some of the azolato-bridged dinuclear platinum(II) complexes (general formula: [{cis-Pt(NH3)2}2(μ-OH)(μ-azolato)]X2, where azolato = pyrazolato, 1,2,3-triazolato, or tetrazolato and X = nitrate or perchlorate) inhibit androgen receptor (AR) signaling. Therefore, here we investigated the potential of 14 such complexes as agents for the treatment of prostate cancer by examining their antiproliferative activity in the human prostate adenocarcinoma cell line LNCaP. Several of the complexes, particularly 5-H-Y ([{cis-Pt(NH3)2}2(μ-OH)(μ-tetrazolato-N2,N3)](ClO4)2), effectively inhibited LNCaP cell growth, even at low concentrations, by direct modulation of AR signaling, and by binding to DNA and inducing apoptosis, which is a common mechanism of action of Pt-based drugs such as cisplatin (cis-diamminedichloridoplatinum(II)). Comparative analysis with cisplatin revealed superior inhibitory effects of these complexes. Further investigation revealed that 5-H-Y suppressed mRNA expression of genes downstream from AR and induced apoptosis, particularly in cells overexpressing AR, highlighting its potential as an AR antagonist. Thus, we provide here insights into the mechanisms underlying the antiproliferative effects of azolato-bridged complexes in prostate cancer.

Although hormone therapy is effective for the treatment of prostate cancer (Pca), many patients develop a lethal type of Pca called castration-resistant prostate cancer (CRPC). Dysregulation of DNA damage response (DDR)-related genes leads to Pca progression. Here, we explored DDR-related signals upregulated in CRPC tissues. We analyzed the gene expression profiles in our RNA-sequence (RNA-seq) dataset containing benign prostate, primary Pca, and CRPC samples. We identified six DDR-related genes (Ribonuclease H2 Subunit A (RNASEH2A), replication factor C subunit 2 (RFC2), RFC4, DNA Ligase 1 (LIG1), DNA polymerase D1 (POLD1), and DNA polymerase E4 (POLE4)) that were upregulated in CRPC compared with Pca tissues. By analyzing public databases and validation studies, we focused on RFC2 as a new biomarker. Functional analysis demonstrated that silencing of RFC2 expression inhibited cell proliferation and induced the expression of DNA damage and apoptosis markers in CRPC model cells. Furthermore, immunohistochemical (IHC) analysis revealed that high expression of RFC2 protein correlated with poor prognosis in patients with Pca and increased expression in CRPC tissues compared with localized Pca. Thus, our study suggests that six DDR-related genes would be important for Pca progression. RFC2 could be a useful biomarker associated with poor outcomes of patients with Pca.

OBJECTIVES: The analysis of the oncological outcomes and postoperative continence recovery between conventional robotic-assisted radical prostatectomy (cRARP) and Retzius-sparing RARP (rsRARP), and the effect of the tumor location on them. MATERIALS AND METHODS: A total of 317 patients who underwent cRARP (n = 228) or rsRARP (n = 89) from August 2017 to July 2020 were assessed. Patients were categorized into groups based on the tumor location by pathology. Positive surgical margin (PSM) rates and biochemical recurrence (BCR)-free survivals and continence recovery were compared between the two procedures. RESULTS: Patient age, prostate-specific antigen (PSA) levels, clinical stages, and Gleason score were not significantly different between the two groups. There was no significant difference in PSM rates (25.8% vs. 33.7%, p = 0.13) or BCR-free survivals (p = 0.28) between cRARP and rsRARP in patients. When tumor was located in the anterior lesion in the prostatectomy pathology, rsRARP was associated with significantly higher PSM rates than cRARP (53.3% in rsRARP vs. 27.0% in cRARP, p = 0.0086), while BCR-free survival did not vary significantly (hazard ratio: 2.15, p = 0.11). When tumors were identified in the posterior in prostatectomy pathology, PSM rates (28.8% in rsRARP vs. 24.7% in cRARP, p = 0.59) or BCR-free survivals (hazard ratio: 0.78, p = 0.51) did not differ significantly between the two groups. rsRARP yielded superior continence recovery in all time points compared to cRARP, which was not affected by the pathological tumor location. CONCLUSION: In posterior tumors, rsRARP results in similar oncological outcomes as cRARP with superior continence recovery, while in anterior tumors, rsRARP may associate with higher PSM rate, combined with improved continence recovery.

The objective of the study was to evaluate the risk of bleeding complications in patients undergoing robot-assisted radical prostatectomy (RARP) while taking antiplatelet (AP) and/or anticoagulant (AC) agents. We analyzed the data of 334 patients undergoing RARP from May 2015 to May 2019. Patients were categorized into AP, AC, and control groups; the bleeding complications were compared among them. The end points were the estimated blood loss, decrease in hemoglobin level, and bleeding complications. The patient characteristics did not differ significantly among groups, with the exception of ASA scores, which were significantly higher in the AP and AC groups vs. the control group. The estimated blood loss and hemoglobin decrease were not significantly different between the AP and AC groups and the control group. The frequency of bleeding complications did not differ significantly between the AP and the control groups, but was significantly higher in the AC vs. the control group (4.3% in the AP and 23.5% in the AC group vs. 3.7% in the control group; P = 0.63 and P < 0.01, respectively). There was no significant difference in bleeding complications between the AP continuation (continuation of a single AP) and the AP interruption group or between the heparin bridging and the AC interruption group. All bleeding complications observed in the AC group occurred after resuming AC therapy. RARP can be performed safely with continuation of a single AP, and in patients taking ACs by interrupting these agents or via heparin bridging, without increasing intraoperative bleeding, whereas postoperative bleeding complications may increase after resuming ACs.

A 71-year-old man presented with neck pain. He was diagnosed with renal cell carcinoma of the left kidney with lung and bone metastases. After laparoscopic left nephrectomy, nivolumab plus ipilimumab was introduced as a first-line therapy for intermediate risk metastatic renal cell carcinoma based on the IMDC risk classification. After four cycles of nivolumab plus ipilimumab, he experienced dyspnea and was diagnosed with interstitial pneumonitis. Corticosteroid therapy was initiated, after which the symptoms of interstitial pneumonitis subsided. Corticosteroid therapy was tapered and discontinued after two months of treatment. The patient experienced fatigue at one week after the discontinuation of corticosteroid therapy and was diagnosed with isolated ACTH deficiency due to hypophysitis. He recovered after hydrocortisone treatment. This case involved two different immune-related adverse events (irAE), interstitial pneumonitis and hypophysitis, that occurred asynchronously following nivolumab plus ipilimumab therapy. It is important to observe the patient's condition carefully whether additional irAEs arise when corticosteroid therapy is tapered or discontinued.

AIM: The aim of this study was to evaluate the dose-volume histogram parameters for late hematuria and rectal hemorrhage in patients receiving radiotherapy after radical prostatectomy. PATIENTS AND METHODS: Data of 86 patients treated between January 2006 and June 2019 were retrospectively evaluated. The median radiation dose was 64 Gy in 32 fractions. Receiver operating characteristic (ROC) curves were used to identify optimal cut-off values for late adverse events. RESULTS: Eleven patients experienced hematuria, and the 5-year cumulative rate was 18%. Four patients experienced rectal hemorrhage, and the 5-year cumulative rate was 7%. ROC curve analysis demonstrated the following significant cut-off values: bladder V50 Gy: 43% (p=0.02) and V40 Gy: 50% (p=0.03) for hematuria, and rectum V60 Gy: 13% (p=0.04) and V50 Gy: 33% (p=0.03) for rectal hemorrhage. CONCLUSION: This is the first study to identify dose constraints that may reduce hematuria and rectal hemorrhage in patients receiving radiotherapy in the postoperative setting.

INTRODUCTION: Tumor lysis syndrome is a rare and potentially fatal complication of oncological treatment. It is characterized by biochemical changes associated with the rapid lysis of malignant cells, usually after chemotherapy. Tumor lysis syndrome is typically noted in patients with hematological malignancies, and it rarely occurs in patients with solid tumors. CASE PRESENTATION: We report a case of tumor lysis syndrome after cabazitaxel administration for metastatic castration-resistant prostate cancer. To our knowledge, tumor lysis syndrome after cabazitaxel therapy has not been reported previously. The patient was a 77-year-old man who developed clinical tumor lysis syndrome after a single dose of cabazitaxel for metastatic castration-resistant prostate cancer. He was treated with hydration and the recombinant uricolytic agent rasburicase, and his condition improved. CONCLUSION: It is extremely important to assess the risk factors for tumor lysis syndrome and to perform active prevention procedures in order to avoid fatal outcomes. It may be beneficial to use rasburicase in patients with established tumor lysis syndrome.

Background: Vanin-1 is a novel acute kidney injury (AKI) biomarker that has not been clinically investigated as a biomarker for obstructive nephropathy. This study investigated the diagnostic value of vanin-1 as a biomarker for adult obstructive nephropathy by comparing it to existing AKI biomarkers. Methods: A total of 49 patients, 21 controls, and 28 hydronephrosis (HN) cases were assessed. AKI biomarkers in bladder (BL) urine and renal pelvic (RP) urine in the HN group were compared to each BL marker in the control group. In a subgroup of cases receiving interventions for obstructive nephropathy, the BL values of each biomarker were assessed after the intervention. Results: RP vanin-1 levels were significantly higher while BL vanin-1 levels were marginally higher in the HN group than in the control group. The area under the receiver operating characteristics curve values for RP and BL vanin-1 were 0.9778 and 0.6386, respectively. In multivariate analyses, BL vanin-1 and N-acetyl-β-D-glucosaminidase (NAG), but not kidney injury molecule-1 (KIM-1) or neutrophil gelatinase-associated lipocalin (NGAL), were independent factors for predicting the presence of HN. In cases receiving interventions, vanin-1 decreased significantly from 1 week after the intervention in cases of moderate to severe obstructive nephropathy compared to RP values at baseline. Conclusion: Urinary vanin-1 is a useful biomarker to detect and monitor the clinical course of obstructive nephropathy.

BACKGROUND: Information on the safety of transurethral resection of bladder tumors (TURBT) in patients receiving anti-thromboembolic drugs is currently lacking. This study aimed to evaluate the clinical safety of TURBT in patients receiving anti-thromboembolic agents compared with patients not taking these agents and patients who interrupted their use perioperatively. METHODS: We retrospectively analyzed data for patients who underwent TURBT at Jichi Medical University Saitama Medical Center from September 2013 to August 2016.Patients who underwent surgery while receiving antiplatelet and/or anticoagulant drugs were allocated to the continuation group, those who interrupted these drugs comprised the interruption group, and those who did not use these agents were designated as the control group. We compared the patient characteristics, hemoglobin levels, and complications among the three groups. RESULTS: A total of 174 patients were analyzed including 19, 18, and 137 in the continuation, interruption, and control groups, respectively. There were no significant differences in patient and tumor characteristics, apart from age, among the three groups. Decreases in hemoglobin levels were similar in the continuation, interruption, and control groups (-0.50 g/dl, -0.40 g/dl, and -0.50 g/dl, respectively).Significantly more patients in the continuation group experienced clot retention compared with the control group (21% vs 5%, p = 0.03). Large tumor size tended to be a risk factor for clot retention in the continuation group (p = 0.07). No patient in the continuation or interruption group required blood transfusion, compared with two patients (1%) in the control group. No patients in any of the groups experienced cardiovascular events during their hospital stay or required rehospitalization for hematuria after discharge. CONCLUSIONS: TURBT can be performed safely in patients who continue to take antiplatelet and/or anticoagulant agents, without increasing the risks of severe hemorrhage and blood transfusion. However, the risk of postoperative clot retention may be increased in these patients.

A late-relapse germ cell tumor might contain malignant non-germ cell tumors, known as 'somatic-type malignancy (SM)'. The development of a secondary SM is rare, and this phenomenon remains poorly understood. Case 1 developed lung metastasis 13 years after chemotherapy followed by retroperitoneal lymph node dissection for stage IIA non-seminoma. The tumor increased in size after chemotherapy. The patient underwent a pneumonectomy. Pathology revealed an adenocarcinoma with immature teratoma. The patient has experienced no relapse for 9 years. Case 2 developed a pelvic tumor after 10 years of surveillance for stage I seminoma. The tumor increased in size after chemotherapy. The patient underwent pelvic tumor resection with cystectomy. Pathology revealed a mature teratoma with SMs consisting of sarcoma and adenocarcinoma. The patient has experienced no relapse for 6 months. Surgical resection played a major role in the treatment of very late-relapse germ cell tumors with SM.

BACKGROUND: To assess whether hemorrhagic complications associated with transperineal prostate biopsy increased in patients on antiplatelet and/or anticoagulant therapy. METHODS: In total, 598 consecutive patients underwent transperineal prostate biopsy. The medication group comprised patients who took anti-thromboembolic agents, and the control group comprised those who did not take these agents. No anti-thromboembolic agent was stopped before, during, or after prostate biopsy in the medication group. Complications developing in both groups were compared and classified using the modified Clavien classification system. Subgroup analyses to compare complications in patients taking single antiplatelet, single anticoagulant, and dual antiplatelet and/or anticoagulant agents, and multivariate analyses to predict bleeding risk were also performed. RESULTS: Of the 598 eligible patients, 149 comprised the medication group and 449 comprised the control group. Hematuria (Grade I) developed in 88 (59.1%) and 236 (52.5%) patients in the medication and control group, respectively (p = 0.18). Clot retention (Grade I) was more frequently observed in the medication group than the controls (2.0% versus 0.2%, respectively, p < 0.05). Hospitalization was more frequently prolonged in the medication than the control group (4.0% versus 0.4% of patients, respectively). No complication of Grade III or higher developed in either group. Hematuria was more frequent in patients taking a single anticoagulant (p = 0.007) or two anti-thromboembolic agents (p = 0.04) compared with those taking a single antiplatelet agent. Other complications were generally similar among the groups. In the multivariate analysis, taking more than two anti-thromboembolic agents was the only significant risk factor for bleeding events. CONCLUSION: No severe complication developed after the transperineal biopsies in either group, although minor bleeding was somewhat more frequent in the medication group. It may not be necessary to discontinue anticoagulant and/or antiplatelet agents when transperineal prostate biopsy is contemplated.