大島 将

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.