Evaluating RB1 and p53 as diagnostic markers in treatment-related neuroendocrine prostate cancer through immunohistochemistry and genomic analysis of RB1 and TP53.

BACKGROUND: The diagnosis of treatment-related neuroendocrine prostate cancer (t-NEPC) often involves a pathological assessment and immunohistochemistry (IHC) for neuroendocrine markers. Genomic alterations in RB1 and TP53 are frequently observed in NEPC and are believed to play a crucial role in the transformation of adenocarcinoma to NEPC. In this study, we examined the clinicopathologic, immunohistochemical, and genetic features of patients with t-NEPC to better understand their prognosis and diagnostic utility. METHODS: This retrospective study reviewed the records of patients diagnosed with t-NEPC at Kobe University Hospital between October 2018 and December 2022. Clinical data, including age, serum neuroendocrine marker levels, and treatment history, were collected. IHC was performed for conventional neuroendocrine markers (synaptophysin, chromogranin A, and CD56) and RB1 and p53 expression. Next-generation sequencing (NGS) was conducted using FoundationOne® CDx to identify mutations in RB1 and TP53. RESULTS: This study included 20 patients with t-NEPC. The median time from ADT initiation to development was 42.8 months. IHC revealed RB1 loss in 75% of cases and p53 abnormalities in 75% of cases. NGS identified RB1 mutations in 55% and TP53 mutations in 75% of cases. The concordance between NGS and IHC results was high, with 70% (14/20) agreement for RB1/RB1 and 80% (16/20) for p53/TP53. The immunostaining and genomic analysis of RB1/RB1 and p53/TP53 showed abnormal findings for the four negative cases for conventional neuroendocrine markers. CONCLUSIONS: This study indicated high concordance between IHC and NGS findings for RB1/RB1 and p53/TP53 in t-NEPC. We provide a comprehensive benchmark of NGS performance compared with IHC, and these findings may help increase the diagnostic sensitivity of t-NEPC.

Temporal declines in bone mineral density and trabecular bone score during androgen deprivation therapy.

INTRODUCTION: The trabecular bone score (TBS) has emerged as a convenient measure for assessing the microstructure of trabecular bone in the second through fourth lumbar vertebrae (L2-4) and can be conducted concurrently with bone mineral density (BMD) assessment. This study was performed to evaluate changes in BMD and the TBS during ADT for prostate cancer. MATERIALS AND METHODS: Consecutive patients who had prostate cancer without bone metastases at Kobe University Hospital were studied from March 2020 to December 2021. BMD and TBS were measured every 6 months from the start of treatment using Hologic Horizon devices (Hologic, Inc., Marlborough, MA, USA). RESULTS: Thirty-four patients were followed for 2 years. Significant declines in BMD (-3.8% for femoral neck, -4.2% for total hip, and -6.1% for lumbar spine) and TBS (-16.6%) were noted after 2 years of ADT. Correlation analyses revealed a weak correlation between lumbar spine BMD and TBS at ADT initiation, but this correlation strengthened after 2 years. The multiple regression analysis results suggested that the rate of BMD loss may be slower in patients with a preserved pretreatment TBS. CONCLUSION: In patients without bone metastases undergoing ADT for prostate cancer, notable decreases were found in both BMD and TBS over a 2-year treatment period. Factors influencing the TBS decline remain unclear; however, patients with a lower pretreatment TBS exhibited a more rapid decline in BMD.

Efficacy of robot-assisted partial nephrectomy compared to conventional laparoscopic partial nephrectomy for completely endophytic renal tumor: a multicenter, prospective study.

BACKGROUND: This study aimed to compare the efficacy of robot-assisted partial nephrectomy for completely endophytic renal tumors with the reported outcomes of conventional laparoscopic partial nephrectomy and investigate the transition of renal function after robot-assisted partial nephrectomy. METHODS: We conducted a prospective, multicenter, single-arm, open-label trial across 17 academic centers in Japan. Patients with endophytic renal tumors classified as cT1, cN0, cM0 were included and underwent robot-assisted partial nephrectomy. We defined two primary outcomes to assess functional and oncological aspects of the procedure, which were represented by the warm ischemic time and positive surgical margin, respectively. Comparisons were made using control values previously reported in laparoscopic partial nephrectomy studies. In the historical control group, the warm ischemia time was 25.2, and the positive surgical margin was 13%. RESULTS: Our per-protocol analysis included 98 participants. The mean warm ischemic time was 20.3 min (99% confidence interval 18.3-22.3; p < 0.0001 vs. 25.2). None of the 98 participants had a positive surgical margin (99% confidence interval 0-5.3%; p < 0.0001 vs. 13.0%). The renal function ratio of eGFR before and after protocol treatment multiplied by splits was 0.70 (95% confidence interval: 0.66-0.75). Factors such as preoperative eGFR, resected weight, and warm ischemic time influenced the functional loss of the partially nephrectomized kidney after robot-assisted partial nephrectomy. CONCLUSIONS: Robot-assisted partial nephrectomy for completely endophytic renal tumors offers a shorter warm ischemia time and comparable positive surgical margin rate compared with conventional laparoscopic partial nephrectomy.

The harmful effects of overlooking acute bacterial prostatitis.

Prostatitis is a major urological disease affecting 25%-50% of men over their lifetime. However, prostatitis is often overlooked in nonurologic departments due to its sometimes indeterminate symptoms. In this review, we describe how to recognize and treat acute bacterial prostatitis, which manifests as a clinical problem in other departments as well as urology, to help prevent this disease from being overlooked. There are several possible negative effects of not recognizing acute bacterial prostatitis (ABP). First, initial treatment can fail. In the hyperacute phase, common antibiotics are often effective, but in rare cases, such antibiotics may not be effective. In addition, once ABP progresses to form a prostate abscess, potentially avoidable surgical interventions are often needed. A second issue is the transition to chronic prostatitis. If chronic bacterial prostatitis progresses, treatment requires long-term antibiotic administration and the response rate is not high. Some patients may have to deal with urinary tract infections for the rest of their lives. Finally, there is the problem of overlooking the underlying disease. ABP is rare in healthy adult men without underlying disease, including sexually transmitted diseases as well as benign prostatic hyperplasia, urinary stones, and malignant tumors, and may not be obvious. When examining patients with fever of unknown origin, it is necessary to exclude not only infectious diseases but also collagen diseases and malignant tumors. If there are any doubts, we recommend a rectal exam and consultation with a urologist.

Effects of modifying hinotori™ surgical robot system on perioperative outcome of robot-assisted radical prostatectomy.

OBJECTIVES: One of the main advantages of the hinotori™ surgical robot system (HSRS) is that it can be easily adjusted. This study aimed to clarify the effects of modifying the HSRS on the perioperative outcomes of robotic-assisted radical prostatectomy (RARP). METHODS: Overall, 158 cases of RARP using the HSRS were classified into three groups based on the modification to the system: group A (no modification, 70 cases), group B (addition of the ability to switch between two types of scopes and to adjust the arm base tilt back and forth, left and right, 42 cases), and group C (reduction of arm floating sensation, mitigation of emergency stop during arm collision, and addition of clutch function via hand switch in addition to foot pedal, 46 cases). The perioperative outcomes of each group were compared. RESULTS: The median of operation time, cockpit time, and cockpit time excluding the time required for lymph node dissection of group C were 223, 146, and 135 min, respectively, where are significantly shorter than those of group A (308, 228, and 208 min, p < 0.0001, respectively) and group B (319, 241, and 214 min, p < 0.0001, respectively). There was no significant difference in the rate of positive margin rates and the pad-free rate before the first follow-up visit among these three groups. The complication rates in groups A, B, and C were 11.4%, 9.4%, and 8.4% (Clavien-Dindo grades I-II), and 4.3%, 2.4%, and 0% (grade III), respectively. CONCLUSIONS: The modifications to the HSRS have enabled smoother surgical procedures for RARP.

Adrenalectomy for pheochromocytoma: Surgical outcomes and preoperative risk factors for hemodynamic instability.

BACKGROUND: Surgical resection for pheochromocytoma (PCC) is still challenging. This study assessed the perioperative outcomes of adrenalectomy for PCC and investigated the risk factors for intraoperative hemodynamic instability (HI). METHODS: This retrospective study included 571 patients with adrenal tumors who underwent adrenalectomy at Kobe University Hospital and other related hospitals between April 2008 and October 2023. The perioperative outcomes of laparoscopic adrenalectomy were compared between PCC (n = 92) and non-PCC (n = 464) groups. In addition, we investigated several potential risk factors for intraoperative HI in patients with PCC (n = 107; open, n = 11; laparoscopic, n = 92; robot-assisted, n = 4). RESULTS: While patients with PCC had a significantly larger amount of blood loss in comparison to those with non-PCC (mean, 70 and 30 mL, respectively; p = 0.004), no significant difference was observed in the rate of perioperative grade ≥III complications (1.1% vs. 0.6%; p = 0.516), and no perioperative mortality was observed in either group. A tumor size of ≥40 mm, with preoperative hypertension and urinary metanephrines at a level ≥3 times the upper limit of the normal value, were found to be significant predictors of HI, with odds ratios of 2.74 (p = 0.025), 3.91 (p = 0.005), and 3.83 (p = 0.004), respectively. CONCLUSIONS: Our data suggest that laparoscopic adrenalectomy for PCC may be as safe as that for other types of adrenal tumors and that large tumors and hormonally active disease may be risk factors for intraoperative HI. The optimal perioperative management for PCC with these risk factors should be established.

Real-world outcomes of avelumab plus axitinib as first-line therapy in patients with advanced renal cell carcinoma in Japan: A multicenter, retrospective, observational study (J-DART).

OBJECTIVES: In the phase 3 JAVELIN Renal 101 trial in patients with advanced renal cell carcinoma (aRCC), objective response rate (ORR) and progression-free survival (PFS) were significantly improved in patients treated with first-line avelumab plus axitinib vs sunitinib. Here we evaluate real-world outcomes with first-line avelumab plus axitinib in Japanese patients with aRCC. METHODS: In this multicenter, noninterventional, retrospective study, clinical data from patients with aRCC treated with first-line avelumab plus axitinib between December 2019 and December 2020 in Japan were reviewed. Endpoints included ORR and PFS per investigator assessment, and time to treatment discontinuation (TTD). RESULTS: Data from 48 patients (median age, 69 years) from 12 sites were analyzed. Median follow-up was 10.4 months (range, 2.6-16.5), and median duration of treatment was 7.4 months (range, 0.5-16.5). International Metastatic RCC Database Consortium risk category was favorable, intermediate, or poor in 16.7%, 54.2%, and 29.2% of patients, respectively. The ORR was 48.8% (95% CI, 33.3%-64.5%), including complete response in 3/43 patients (7.0%). Thirteen patients (27.1%) had disease progression or died, and median PFS was 15.3 months (95% CI, 9.7 months - not estimable). At data cutoff, 24 patients (50.0%) were still receiving avelumab plus axitinib, and median TTD was 15.2 months (95% CI, 7.4 months - not estimable). Three patients (6.3%) received high-dose corticosteroid treatment for immune-related adverse events, and 8 (16.7%) received treatment for infusion-related reactions. CONCLUSIONS: We report the first real-world evidence of the effectiveness and tolerability of first-line avelumab plus axitinib in Japanese patients with aRCC. Results were comparable with the JAVELIN Renal 101 trial.

Real-world analysis of metastatic prostate cancer demonstrates increased frequency of PSA-imaging discordance with visceral metastases and upfront ARAT/docetaxel therapy.

BACKGROUND: The objective of this study was to evaluate the background and treatment course of patients with metastatic prostate cancer (PC), with a particular focus on radiographic progression in the absence of prostate-specific antigen (PSA) progression. METHODS: The study population consisted of 229 patients with metastatic hormone-sensitive PC (HSPC), who received prostate biopsy and androgen deprivation therapy at Kobe University Hospital between January 2008 and June 2022. Clinical characteristics were retrospectively evaluated using medical records. PSA progression-free status was defined as ≤1.05 times greater than that from 3 months before. Multivariate analyses were performed using the Cox proportional hazards regression model to identify parameters associated with time to progression on imaging without PSA elevation. RESULTS: A total of 227 patients with metastatic HSPC without neuroendocrine PC were identified. The median follow-up period was 38.0 months, with a median overall survival of 94.9 months. Six patients exhibited disease progression on imaging without PSA elevation during HSPC treatment, three during first-line castration-resistant PC (CRPC) treatment, and two during late-line CRPC treatment. The rate of disease progression without PSA elevation at 3 years after treatment initiation was 7.4%. Multivariate analysis revealed that organ metastases and upfront treatment with docetaxel or androgen receptor axis-targeted therapy were independent prognostic factors for imaging progression without PSA elevation. CONCLUSIONS: Disease progression on imaging without PSA elevation occurred not only during HSPC treatment and first-line CRPC treatment, but also during late-line CRPC treatment. Patients with visceral metastases or those treated with upfront androgen receptor axis-targeted or docetaxel may be more prone to such progression.

Proapoptotic effect of nonthermal pulsed ultrasound on prostate cancer cells in a nude mouse model.

BACKGROUND: Ultrasound (US) can induce cell injury, and we have previously reported that adjusting the pulse repetition frequency (PRF) of ultrasound output can induce prostate cancer cell destruction without causing a rise in the temperature of the irradiated area. In this study, we examined the mechanism of nonthermal ultrasound cell destruction, which was not fully clarified in our previous reports. METHODS: In vitro, we evaluated postirradiation cells immediately after treatment and examined membrane disruption by proliferation assay, LDH assay, and apoptosis assay. In vivo, we injected mice with human LNCaP and PC-3 prostate cancer cells and evaluated the therapeutic effects of US irradiation by H-E staining and immunostaining. RESULTS: Proliferation assays showed inhibition at 3 h postirradiation independently of PRF and cell line (p < 0.05). Quantitative assessment of apoptosis/necrosis by flow cytometry showed widely varying results depending on cell type. LNCaP showed an increase in late apoptosis at 0 h independent of PRF (p < 0.05), while PC-3 showed no significant difference at 0 h. The LDH assay showed an increase in LDH independent of PRF in LNCaP (p < 0.05 respectively), but no significant difference in PC-3. In vivo, tumor volume was compared and a significant reduction was observed at 10 Hz for LNCaP (p < 0.05) and 100 Hz for PC-3 (p < 0.001) at 3 weeks after the start of irradiation. The excised tumors were evaluated with Ki-67, Caspase-3, and CD-31 and showed a significant treatment effect independent of cell type and PRF (p < 0.001 respectively). CONCLUSION: Examining the mechanism behind the therapeutic effect of US irradiation revealed that the main effect was achieved by apoptosis induction rather than necrosis.

Bioabsorbable zinc alloys for use in urological surgery.

PURPOSE: Non-absorbable clips are widely used in urologic surgery and they may come in contact with an open urinary tract intraoperatively. As a result, stray clips in the urinary tract and associated intractable infections have been reported. We developed a bioabsorbable metal and evaluated whether it would dissolve if it strayed into the urinary tract. METHODS: We prepared four types of alloys mainly comprising zinc (Zn) with small amounts of magnesium (Mg) and strontium (Sr), and the biological effects, degradability, strength, and ductility were investigated. Each alloy was implanted in the bladder of five rats for 4, 8, and 12 weeks. The alloys were removed and evaluated for degradability, stone adhesion, and tissue changes. The Zn-Mg-Sr alloy had degradability and no stone adhesion in the rat experiments, and it was implanted in the bladders of five pigs for 24 weeks. The Mg and Zn levels in the blood were measured, and staple changes were confirmed by cystoscopy. RESULTS: Zn-Mg-Sr alloys showed the best degradability of 6.51% at 12 weeks. In pig experiments, the degradation rate was 3.72% at 24 weeks. None of the pigs had changes in the Zn or Mg concentrations in the blood. Overall, the bladder incision was healed and the gross pathology showed wound healing. CONCLUSIONS: The Zn-Mg-Sr alloys were safely used in animal experiments. Furthermore, the alloys are easy to process and can be formed into various shapes, such as staples, making them useful in robotic surgery.

Treatment outcome after sequential chemotherapy with cisplatin-etoposide, amrubicin and nogitecan in patients with treatment-related pure small-cell neuroendocrine prostate cancer.

OBJECTIVE: This study retrospectively reviewed the clinical characteristics and treatment outcomes of patients with histologically diagnosed treatment-related pure small-cell neuroendocrine prostate cancer. METHODS: We retrospectively evaluated data for 13 patients with treatment-related neuroendocrine prostate cancer who were diagnosed between May 2015 and February 2022. Standardized systemic therapies of etoposide plus cisplatin (or carboplatin), amrubicin and nogitecan were selected as sequential treatments. Cancer-specific survival and progression-free survival were evaluated as the primary endpoint. The Cox proportional hazards model was used to evaluate the relationships between treatment regimens, clinical variables, cancer-specific survival and progression-free survival. RESULTS: The median cancer-specific survival after diagnosis for all patients was 22.4 months (range 1.3-33.4 months). The median progression-free survival was 9.3 months after first-line etoposide plus cisplatin (or carboplatin) treatment (n = 13); 4.2 months after second-line amrubicin treatment (n = 4); and >15 months after third-line nogitecan treatment (n = 2). The median progression-free survival after first-line chemotherapy of the liver metastasis (-) group was 10.2 months, and that of the (+) group was 5.3 months (P = 0.015, hazard ratio = 11.6, 95% confidence interval = 1.01 - 133.7). No clinicopathological parameters were identified as significant independent predictors of cancer-specific survival in univariate analysis. CONCLUSION: Sequential chemotherapy with etoposide plus cisplatin (or carboplatin), amrubicin and nogitecan may be helpful for patients with treatment-related pure small-cell neuroendocrine prostate cancer. Early biopsy of metastases and initiation of effective therapy is essential for patients with progressive castration-resistant prostate cancer and low prostate-specific antigen.

Urinary tract infections after retrograde pyelography and prophylactic antibiotics.

INTRODUCTION: Retrograde pyelography (RP) is performed for examination of upper urinary tract cancers and hydronephrosis. Although urinary tract infections (UTI) are known to be complicated by the examination, there are few reports on the frequency of occurrence and prophylactic antibiotics. METHODS: The incidence of UTI and febrile UTI (f-UTI) and patient background information were compared in 388 patients who underwent RP at our hospital from January 2018 to December 2022. We also examined the administration of pre-RP antibiotics. RESULTS: Of the 388 patients who underwent RP, 27 (6.9%) had UTI and 17 (4.4%) had f-UTI. Of the 27 UTI cases, 25 (92.6%) were pyelonephritis; 20 (74.0%) were hospitalized and 2 (7.4%) presented with septic shock and were managed in the intensive care unit. When comparing the background of patients with UTI, no significant differences were found in the present study, but when limited to the 17 cases of f-UTI, the presence of hydronephrosis before RP and not prescribing antibiotics before RP were associated with significantly higher incidence of f-UTI (p = 0.019, p = 0.036, respectively). Especially for patients without pyuria and bacteriuria before RP, prescribing antibiotics before RP resulted in 0 cases of f-UTI (p = 0.020). CONCLUSION: This retrospective study showed that the presence of hydronephrosis before RP and not prescribing prophylactic antibiotics before RP are risk factors for f-UTI.

Avelumab plus Axitinib for the Treatment of Patients with End-Stage Renal Disease Undergoing Dialysis: A Retrospective Case Series and Literature Review.

Combination therapies of an immune checkpoint inhibitor and a molecular targeted agent are widely accepted as an appropriate initial systemic therapy for metastatic renal cell carcinoma (RCC), but there is little published evidence regarding the efficacy of this approach in patients with end-stage renal disease (ESRD). Here, we report three patients who were undergoing hemodialysis for ESRD whose metastatic RCC was successfully treated using avelumab plus axitinib. The patients were a 67-year-old man with swollen lymph nodes, a 65-year-old man with pleural dissemination, and a 71-year-old man with lung nodules and an infra-diaphragmatic nodule. They were administered a combination of avelumab plus axitinib as their initial systemic therapy following definitive surgical therapy. The best response of three patients was graded as partial response. No severe adverse events were identified. This is the first report of the use of combination therapy consisting of avelumab plus axitinib in patients with ESRD undergoing hemodialysis. We found that this combination was useful in such patients.

Impact of cytoreductive nephrectomy prior to combination therapy of ipilimumab plus nivolumab in metastatic renal cell carcinoma.

OBJECTIVES: The efficacy of cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors (ICIs) has been suggested in the real-world setting. We retrospectively examined the efficacy of CN prior to nivolumab plus ipilimumab systemic therapy for synchronous mRCC. METHODS: Synchronous mRCC patients who received nivolumab plus ipilimumab at Kobe University Hospital or five affiliated hospitals between October 2018 and December 2021 were included in this study. We compared the outcomes of objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) between patients with CN prior to systemic therapy and without CN. In addition, patients were 1:1 matched by propensity scores accounting for factors associated with treatment assignment. RESULTS: Twenty-one patients received CN prior to nivolumab plus ipilimumab (Prior CN) and 33 received nivolumab plus ipilimumab alone (Without CN). PFS of the Prior CN group was 10.8 months (95%CI 5.5-NR) and 3.4 months (95%CI 2.0-5.9) for the Without CN group (p = 0.0158). OS of Prior CN was 38.4 months (95%CI NR-NR) and 12.6 months (95%CI 4.2-30.8) for Without CN (p = 0.0024). Univariate and multivariate analyses identified prior CN as a significant prognostic indicator for PFS and OS. Moreover, propensity score matching analysis showed significant improvements in PFS and OS in Prior CN. CONCLUSIONS: Patients who underwent CN prior to nivolumab plus ipilimumab systemic therapy for synchronous mRCC had a better prognosis than patients treated with nivolumab plus ipilimumab alone. These results suggest the efficacy of prior CN for synchronous mRCC with ICI combination therapy.

The poor antitumor effect of pembrolizumab in advanced upper urothelial carcinoma with renal parenchymal invasion.

OBJECTIVES: We investigated poor prognosticators in advanced or unresectable urothelial carcinoma, focusing on renal parenchymal invasion (RPI). METHODS: This study included 48 bladder cancer (BC) and 67 upper tract urothelial carcinoma (UTUC) patients treated with pembrolizumab from December 2017 to September 2022 at Kobe University Hospital. Medical records were retrospectively reviewed for clinical characteristics, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Multivariate analyses were performed using the Cox proportional hazard regression model to identify parameters associated with either PFS or OS. RESULTS: Of 67 UTUC patients, 23 had RPI and 41 patients did not, while 3 cases could not be evaluated. Patients with RPI were predominantly elderly and had liver metastases. ORR for patients with RPI was 8.7%, while it was 19.5% for those without RPI. PFS was significantly shorter for patients with RPI compared with those without RPI. Patients with RPI had significantly shorter OS than those without RPI. On multivariate analysis, performance status (PS) ≥ 2, neutrophil-lymphocyte ratio (NLR) ≥ 3, C-reactive protein ≥0.3 mg/dL and RPI were independent prognostic factors for PFS. PS ≥ 2, NLR ≥ 3, visceral metastasis and RPI were independent prognostic factors for OS. UTUC patient OS was significantly shorter than BC patient OS, while no significant difference in PFS or OS was observed between BC patients and UTUC patients without RPI. CONCLUSIONS: RPI was a poor prognostic factor in advanced urothelial carcinoma treated with pembrolizumab, possibly resulting in a poorer prognosis for UTUC compared with BC.

A comparison of the impact of the COVID-19 pandemic on urological surgeries in Japan and Taiwan.

OBJECTIVE: We report the impact of the COVID-19 pandemic on urological surgeries and hospital policies at two hospitals in Japan and Taiwan. METHODS: We retrospectively surveyed the number of surgeries every 3 months in the Urology Department of Kobe University Hospital (KUH), Kobe, Japan before (January 2019-March 2020) and after (April 2020-September 2021) the COVID-19 outbreak, and in the Urology Department of Shuang Ho Hospital, Taipei Medical University (SHH-TMU), Taiwan before (January 2021-March 2021) and after (April 2021-September 2021) the outbreak, and compared the averages and types of surgery. RESULTS: In Kobe, COVID-19 patients were stratified such that other regional hospitals gave priority to treating COVID-19 while KUH gave priority to treating non-COVID-19 patients. In KUH, the number of surgeries did not change significantly, 237.2 ± 29.6 versus 246.3 ± 20.8 (p = 0.453). In Taiwan COVID-19 patients increased sharply in May 2021, and teaching hospitals in Taiwan were obliged to provide 20% of their total beds for COVID-19 patients. At SHH-TMU, there was a 33.3% drop in the number of surgeries during April-June 2021 compared to the pre-pandemic average. However, no significant changes were observed, 423.4 ± 68.4 versus 373 ± 91.0 (p = 0.298), because of the subsequent success in controlling the COVID-19 infection. CONCLUSIONS: The comparison of infection control measures between the two countries revealed that while both KUH and SHH-TMU successfully maintained the number of surgeries, the reasons for this were different for each.

The Efficacy of Surgical Metastasectomy for Solitary Metastasis of Renal Cell Carcinoma.

BACKGROUND: Patients with solitary metastasis of renal cell carcinoma (RCC) have shown to be ideal candidates for surgical metastasectomy (SM). However, whether SM will show more benefit than systemic therapy remains unclear. METHODS: We included 73 patients treated for solitary metastasis after nephrectomy at our institute from April 2008 to December 2018. We compared the clinical outcomes between the SM (n = 29) and no-SM (n = 44) group which were treated with only systemic therapy. RESULTS: Eleven of 29 patients in the SM group received presurgical targeted therapy (PTT). Although 13 of 29 patients in the SM group showed recurrence during the study period, a Cox proportional hazards model showed that SM was significantly associated with a favorable overall survival (hazard ratio: 0.18; p = 0.007). Patients receiving PTT prior to SM showed a longer recurrence-free survival after SM in comparison to those who underwent SM without PTT (median: not reached vs. 27.7 months; p = 0.009). CONCLUSIONS: If resection is feasible, SM may be beneficial for patients with solitary metastasis of RCC, and we showed the possibility that PTT prior to SM may be effective for avoiding recurrence after SM. Further large-scale prospective studies are needed to clarify the ideal treatment strategy for metastatic RCC.

Development of bioabsorbable zinc-magnesium alloy wire and validation of its application to urinary tract surgeries.

PURPOSE: Metallic medical devices are typically constructed from non-bioabsorbable metals that remains in the body and causes considerable complications. Particularly in the urinary tract, calculus, intractable infection, and misdiagnosis as calculus are often caused by non-bioabsorbable metals. Here, we developed a zinc-magnesium alloy as a new bioabsorbable metal and sought to evaluate the bioabsorbable behavior of zinc and zinc-magnesium alloy in a rat bladder implantation model. METHODS: We prepared zinc-magnesium alloy wires with various proportions of magnesium and investigated the strength, shape retention, formability, and absorbability of these novel materials. Then, we implanted zinc and zinc-magnesium alloy rings formed by the wires into rat bladder. Rats were euthanized at the end of the observation period, and the rings were removed for volume evaluation. Extracted bladder tissues were subjected to histological analysis. RESULTS: The strength of the zinc wire was enhanced by more than fourfold upon the addition of magnesium, without loss of ductility. Linear reduction of ring volume in urine was observed based on the concentration of magnesium within the ring. Nearly all rings were covered with a thin layer of calculus. Histological findings of the transected urinary bladder tissues did not differ among groups. CONCLUSIONS: Zinc-magnesium alloy is a promising candidate for use as a bioabsorbable medical device in the urinary tract.

Treatment outcomes of molecular targeted therapy following nivolumab in metastatic renal cell carcinoma.

OBJECTIVE: The purpose of this study was to assess the therapeutic efficacy of molecular targeted therapies following nivolumab in metastatic renal cell carcinoma and to examine the relationship between therapeutic efficacy and the specific molecular targeted therapy used. METHODS: We retrospectively reviewed the medical records of 115 metastatic renal cell carcinoma patients who were treated with nivolumab at our institution and five affiliated hospitals. Among them, 52 patients who received subsequent molecular targeted therapy following nivolumab were selected to survey treatment outcomes. Progression-free survival and overall survival were estimated with Kaplan-Meier curves, and differences were analyzed by the log-rank test. RESULTS: Among the 52 eligible patients, 40 (76.9%) were treated with tyrosine kinase inhibitors and 12 (23.1%) were treated with mammalian target of rapamycin inhibitor. The median time to treatment failure and progression-free survival of subsequent molecular targeted therapy were 5.6 and 8.0 months, respectively. The median overall survival from the initiation of first-line therapy was not reached. The disease control rate of subsequent molecular targeted therapy was 69.2% (partial response: 25.0%, stable disease: 44.2%). The median progression-free survival of subsequent tyrosine kinase inhibitor and mammalian target of rapamycin inhibitor were 9.2 and 8.0 months, respectively (P = 0.37). The progression-free survival of patients whose best response to prior nivolumab was either progressive disease or stable disease/partial response were 6.3 and 11.3 months, respectively (P = 0.36). CONCLUSIONS: Molecular targeted therapies following nivolumab had comparatively better therapeutic efficacy, which was confirmed regardless of the type of molecular targeted agent used.

Diagnostic and therapeutic value of pelvic lymph node dissection in the fossa of Marcille in patients with clinically localized high-risk prostate cancer: Histopathological and molecular analyses.

BACKGROUND: The optimal extent of lymph node dissection in radical prostatectomy has not been determined. Lymph nodes in the fossa of Marcille, which is an important pelvic lymphatic pathway and candidate for additional dissection, have not been evaluated at the molecular level. Here, we assessed by molecular analysis the presence of occult positive lymph nodes in the fossa of Marcille in patients with clinically localized high-risk prostate cancer. METHODS: Fifty-two patients with clinically localized high-risk prostate cancer underwent pelvic lymph node dissection accompanied by robot-assisted radical prostatectomy. All nodal packets were dissected separately and grouped into right and left obturator, external and internal iliac regions (including common iliac region to ureter crossing), and fossa of Marcille. All lymph nodes were bisected and evaluated by histopathological or molecular analysis using a quantitative reverse transcription-polymerase chain reaction. The number of positive lymph nodes in the fossa of Marcille and the difference in detection rate were investigated using histopathological and molecular analyses. Perioperative complication rate and predictive factors for biochemical recurrence were evaluated. RESULTS: In the molecular analysis, there were seven positive lymph nodes in the fossa of Marcille in three patients, which were coexistent with positive nodes in other regions. The detection rate of positive lymph nodes was significantly higher using molecular than histopathological analysis (P < .01). Perioperative complication rate within 90 days after the operation was 25.0% and no Clavien-Dindo grade ≥3 complication was confirmed. Detection of metastasis by histopathological and molecular analysis was a significant factor related to biochemical recurrence in the Cox proportional hazards regression model. CONCLUSIONS: No case of positive lymph nodes in the fossa of Marcille that had skipped over other regions was confirmed. Additional lymph node dissection of fossa of Marcille did not lead to complete resection of molecularly positive lymph nodes.