Impact of Robotic-Assisted Partial Nephrectomy with Single Layer versus Double Layer Renorrhaphy on Postoperative Renal Function.

We aimed to investigate the differences in renal function between patients who underwent single inner-layer renorrhaphy (SILR) or double-layer renorrhaphy (DLR) among those with renal tumors who underwent robot-assisted partial nephrectomy (RAPN). This retrospective multicenter cohort study was conducted between November 2018 and October 2023 at two institutions and included patients who underwent RAPN. In total, 93 eligible patients who underwent RAPN were analyzed. Preoperative renal function and prevalence of chronic kidney disease were not significantly different between the two groups. Although urinary leakage was observed in three patients (5.9%) in the SILR group, there was no significant difference between the two groups regarding surgical outcomes (p = 0.249). Serum creatinine levels after RAPN were significantly lower in the SILR group than in the DLR group on postoperative days 1 and 365 following RAPN (p = 0.04). The estimated glomerular filtration rate (eGFR) was significantly lower in the DLR group than in the SILR group only on postoperative day 1; however, there was no significant difference between the two groups thereafter. Multivariate analysis showed that the method of renorrhaphy was not a predictor for maintaining renal function after RAPN even though it was associated with eGFR on postoperative day 1.

The Efficacy and Safety of Immune Checkpoint Inhibitor and Tyrosine Kinase Inhibitor Combination Therapy for Advanced or Metastatic Renal Cell Carcinoma: A Multicenter Retrospective Real-World Cohort Study.

We evaluated the efficacy and safety of combination therapy with immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKI) as first-line therapy for patients diagnosed as having advanced or metastatic renal cell carcinoma (mRCC). We enrolled 51 patients to receive ICI+TKI therapy for mRCC at 9 Japanese institutions. The overall survival (OS) of the patients treated with ICI+TKI was the primary endpoint., and the secondary endpoints were progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Furthermore, we analyzed the clinical prognostic and predictive factors in patients with mRCC treated with ICI+TKI therapy. Seven months was the median follow-up period. The OS rates at 6, 12, and 18 months were 93.1, 82.5, and 68.8%, respectively. The median PFS for patients who received ICI+TKI was 19.0 months, ORR was 68.6%, and DCR was 88.2%. ICI+TKI-related adverse events occurred in 43 patients (84.3%) with any grade and in 22 patients (43.1%) with grade ≥3. Treatment selection with poor prognostic factors may be prudent, even though ICI+TKI is an efficacious and safe first-line treatment in patients with mRCC.

Glycocalyx analysis of bladder cancer: three-dimensional images in electron microscopy and vicia villosa lectin as a marker for invasiveness in frozen sections.

Introduction: The abnormal glycocalyx (GCX) on the surface of cancer cells has been reported to be tall and aberrantly glycosylated and has been linked to the progression and spread of cancer-a finding also observed in bladder cancer. However, the characteristics of GCX in various types of human bladder cancer remain unknown, and herein, we aimed to provide information on the diversity of glycan components in the GCX of bladder cancers and to shed light on their characteristics. Methods: We used scanning electron microscopy and lanthanum staining to examine the surface GCX of human bladder carcinomas in three-dimensional images, showing the bulky GCX in some carcinomas. We also examined glycan alterations in early to progressive stages of bladder cancers using 20 distinct lectin stains on frozen sections from transurethral resection of bladder tumors. Results and discussion: Distinctive Vicia villosa lectin (VVL) staining was observed in invasive urothelial carcinomas, including those with muscle invasion and variant components. In the clinical setting, cancers with atypia of grades 2-3 had a significantly higher VVL scoring intensity than those with grade 1 atypia (p < 0.005). This study identified that a specific lectin, VVL, was more specific to invasive urothelial carcinomas. This lectin, which selectively binds to sites of cancer progression, is a promising target for drug delivery in future clinical investigations.

Efficacy and Safety of Cabozantinib in Patients with Advanced or Metastatic Renal Cell Carcinoma: A Multicenter Retrospective Cohort Study.

A multicenter retrospective study was conducted to evaluate the efficacy and safety of cabozantinib in patients with advanced or metastatic renal cell carcinoma (mRCC). We enrolled 53 patients with mRCC who received cabozantinib at eight institutions in Japan. The primary endpoint was overall survival (OS). The secondary endpoints were objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS). In addition, we analyzed prognostic factors in patients with mRCC treated with cabozantinib. The median follow-up period was 8 months, and the median OS was 20.0 months. The ORR and DCR were 39.6% and 83.0%, respectively. The median PFS was 11.0 months. PFS was significantly shorter in patients previously treated with at least two tyrosine kinase inhibitors and in those with C-reactive protein (CRP) ≥ 1.27 mg/dL (p = 0.021 and p = 0.029, respectively). Adverse events of any grade and grades ≥3 occurred in 42 (79.2%) and 10 (18.9%) patients, respectively. Cabozantinib is a useful treatment option for patients with mRCC and may benefit from earlier use. In this study, CRP ≥ 1.27 mg/dL is a poor prognostic factor in patients treated with cabozantinib, and careful follow-up may be required in treating patients with high CRP.

Effectiveness and Safety of Molecular-Targeted Therapy after Nivolumab Plus Ipilimumab for Advanced or Metastatic Renal Cell Carcinoma: A Multicenter, Retrospective Cohort Study.

This study aimed to evaluate the effectiveness and safety of molecular-targeted therapies (MTTs) after the discontinuation of nivolumab and ipilimumab (NIVO+IPI) combination therapy in patients who had been diagnosed with advanced/metastatic renal cell carcinoma as real-world outcomes. We enrolled patients treated with MTTs following initial therapy with NIVO+IPI at nine institutions in Japan. We evaluated the objective response rate (ORR) as the primary endpoint and disease control rate (DCR), best overall response, and oncological outcomes (overall survival (OS) and progression-free survival (PFS)) as the secondary endpoints. We also evaluated factors predictive of disease progression after the administration of MTTs. Patients were followed up for a median of 8 months. The ORR was 44.8%, and the DCR was 72.4%. The median OS and PFS of MTTs after NIVO+IPI were 18 months and 8 months, respectively. A total of 31% of patients experienced grade 3/4 MTT-related adverse events. The median PFS in patients with bone metastases was significantly shorter than that in those without bone metastases (4 vs. 12 months, p = 0.012). MTTs may be a useful secondary treatment option after the discontinuation of NIVO+IPI.

Oncological Outcomes in Patients with Metastatic Urothelial Carcinoma after Discontinuing Pembrolizumab as a Second-Line Treatment: A Retrospective Multicenter Real-World Cohort Study.

The treatment options are currently limited, and the oncological outcomes remain unclear, for patients with metastatic urothelial carcinoma (mUC) with or without third-line systemic therapy. We aimed to evaluate the oncological outcomes in real-world daily clinical practice after platinum-based chemotherapy followed by pembrolizumab for mUC. This retrospective, multicenter cohort study included patients with mUC who received second-line pembrolizumab in Japan. The patients were divided into the treatment group (those who received third-line treatment) and the BSC group (those who did not receive other treatments). The primary endpoint of this study was to evaluate the oncological outcomes. Of 126 patients enrolled in this study, 40 received third-line therapy. The median follow-up period was 8.0 months. The median overall survival (OS) times were nine months in the BSC group and 17 months in the treatment group (p < 0.001). The median progression-free survival (PFS) times were 4 months in the BSC group and 14 months in the treatment group (p < 0.001). In the multivariate analysis, performance status and liver metastasis were significantly associated with OS. Third-line therapy may have clinical potential advantages for improving the oncological outcomes in patients with mUC.

Clinical Lymph Node Involvement as a Predictor for Cancer-Specific Survival in Patients with Penile Squamous Cell Cancer.

We aimed to identify prognostic predictive factors of patients with penile squamous cell carcinoma (PSCC). This retrospective study reviewed the clinical and pathological data of patients with PSCC at 10 institutions in Japan between January 2008 and December 2019. The primary endpoint was cancer-specific survival (CSS). We also identified useful predictive factors for CSS in patients with PSCC. In total, 64 patients with PSCC were enrolled. At the end of the follow-up period, 15 patients (23.4%) died owing to PSCC and six (9.4%) died owing to other causes. The 2- and 3-year CSS rates were 78.9% and 76.6%, respectively. Using the Kaplan−Meier method, the Eastern Cooperative Oncology Group performance status 0, serum albumin levels ≥4.2 g/dL, hemoglobin levels ≥13.2 g/dL, C-reactive protein levels <0.21 mg/dL, clinical T stage ≤2, clinically negative lymph node (LN) status, and tumor size <30 mm were associated with a significantly better CSS. In the multivariate analysis, the clinically positive LN status was a significant predictive factor for CSS in patients with PSCC. Further prospective large-scale and long-term studies are required to validate our findings.

The Impact of Neutrophil-to-Lymphocyte Ratio after Two Courses of Pembrolizumab for Oncological Outcomes in Patients with Metastatic Urothelial Carcinoma.

We focused on the therapeutic effect of pembrolizumab for metastatic urothelial carcinoma (mUC) and evaluated predictive factors for improving clinical outcomes. We conducted a retrospective multicenter cohort study of patients with mUC who received pembrolizumab. The endpoint was to evaluate the association between clinicopathological features and oncological outcomes. A total of 160 patients were enrolled in this study and were divided into two groups: the responder and the non-responder group, according to the best response. They were followed up for a median period of 10 months. The median overall (OS) and progression-free survival (PFS) in this study were 17 and 4 months, respectively. The responder group did not achieve median OS and it was 10 months in the non-responder group (p < 0.001). Similarly, the responder group did not achieve PFS, and it was 2 months in the non-responder group (p < 0.001). Regarding the neutrophil-to-lymphocyte ratio (NLR) after two courses of administration of pembrolizumab, patients with NLR < 3.24 had significantly better oncological outcomes than those with NLR ≥ 3.24. Multivariate analysis showed a significant association between NLR after two courses of pembrolizumab and OS. Therefore, the absolute value of NLR after two courses of pembrolizumab was a significant predictive factor for oncological outcomes.

The Impact of Postoperative Renal Function Recovery after Laparoscopic and Robot-Assisted Partial Nephrectomy in Patients with Renal Cell Carcinoma.

Background and objectives: This study aimed to evaluate the association between warm ischemic time (WIT) and postoperative renal function using Trifecta achievement in patients with renal cell carcinoma (RCC) who underwent robotic (RAPN) or laparoscopic partial nephrectomy (LPN). Materials and Methods: We conducted a retrospective multicenter cohort study of patients with RCC who underwent RAPN (RAPN group) or LPN (LPN group) at three institutions in Japan between March 2012 and October 2021. The primary endpoints were the rate of trifecta achievement in both surgical techniques and the association between WIT and recovery of postoperative renal function surgical outcomes. Results: The rate of trifecta achievement was significantly lower in patients with LPN than in those with RAPN (p < 0.001). WIT ≥ 25 min were 18 patients (18%) in the RAPN group and 89 (52.7%) in the LPN group. The postoperative estimated glomerular filtration rate (eGFR) was almost the same. However, 13 patients (7.7%) had a decreased in eGFR ≥ 15% at 3 months after LPN compared with the preoperative eGFR. Conclusions: The rate of trifecta achievement in the RAPN group was significantly higher than that in the LPN group. However, eGFR was identified as relatively better preserved after PN in both groups.

Utility of Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, and Systemic Immune Inflammation Index as Prognostic, Predictive Biomarkers in Patients with Metastatic Renal Cell Carcinoma Treated with Nivolumab and Ipilimumab.

The aim of this study was to assess the utility of neutrophil-to-lymphocyte ratio (NLR), plate-let-to-lymphocyte ratio (PLR), and systemic immune inflammation index (SII) as predictive biomarkers with oncological outcomes for metastatic renal cell carcinoma (mRCC) patients treated with nivolumab and ipilimumab (NIVO + IPI). We conducted a retrospective multicenter cohort study assessing patients with mRCC treated with NIVO + IPI at eight institutions in Japan. In this study, the follow-up period was median 14 months. The 1-year overall- and progression-free survival (PFS) rates were 89.1% and 63.1, respectively. The objective response rate (ORR) and disease control rate (DCR) were 41.9% and 81.4%, respectively. The 1-year PFS rates were 85.7% and 49.1% for NLR ≤ 2.8 and >2.8, respectively (p = 0.005), and 75.5% and 49.7% for PLR ≤ 215.6 and >215.6, respectively (p = 0.034). Regarding SII, the 1-year PFS rates were 90.0% and 54.8% when SII was ≤561.7 and >561.7, respectively (p = 0.023). Therefore, NLR, PLR, and SII levels in mRCC patients treated with NIVO + IPI may be useful in predicting oncological outcomes.

[Paraurethral Leiomyoma in a Female Patient who Had Clinical Symptoms with Increase of Tumor Volume: A Case Report].

A 34-year-old woman underwent total hysterectomy for management of uterine leiomyoma. At the same time, a paraurethral tumor (2 cm in size) was diagnosed based on magnetic resonance imaging (MRI). However, the patient was not treated for the tumor considering its small size. Eight years later, the patient was referred to our institution with a chief complaint of urethral bleeding. Computed tomography revealed a paraurethral mass at the same location, which was 13 cm in size. A percutaneous needle biopsy was performed and the tumor was diagnosed as leiomyoma. Tumor extirpation was performed and immunohistochemical analysis of the specimen demonstrated positive estrogen and progesterone receptors. Recurrence was not observed on MRI taken 6 months after the surgery. Paraurethral leiomyoma is rare, but relatively common in young women.

[Renal Cell Carcinoma in the Left Pelvic Kidney : A Case Report].

We report the case of a 61-year-old man who was incidentally diagnosed with a left pelvic ectopic kidney with renal tumor. Computed tomography showed a hypervascular tumor at the posterior surface of the ectopic kidney with five arterial and two venous supply vessels. On preoperative examination, this patient had respiratory dysfunction. For these reasons, an open radical nephrectomy was performed. Histological examination revealed a clear cell renal cell carcinoma, pT1aN0M0, G1, and a Fuhrman nuclear grading system grade of G2. No evidence of disease was observed 15 months after surgery.

The utility of laparoscopic partial nephrectomy with renal function preservation, regardless of warm ischemia time, compared with laparoscopic radical nephrectomy.

INTRODUCTION: This study aimed to evaluate the chronologic changes in renal function after laparoscopic partial (LPN) or radical nephrectomy (LRN) in patients with clinical T1 renal cell carcinoma. METHODS: In this retrospective study, patients with clinical stage T1 renal cell carcinoma who underwent LPN or LRN were divided into three groups, namely, LPN-A group including LPN patients with WIT ≤25 minutes, LPN-B group including LPN patients with WIT >25 minutes, and LRN group. Perioperative complications that occurred within 30 days after surgery were retrieved. All patients were followed-up every 3 months to evaluate the estimated glomerular filtration rate. The primary endpoint of this study was to assess the chronological changes in renal function after surgery. RESULTS: A total of 153 patients were enrolled in this study. The change in estimated glomerular filtration rate between day 1 and 2 weeks after surgery was significantly lower in the LPN-B group than in the LPN-A group (p<0.005). Both LPN-A and -B groups achieved eGFR ≥90% 2 weeks after surgery. In addition, the estimated glomerular filtration rate decline from post-operative day 1 through 24 months in the LPN-A group or the LPN-B group was significantly smaller than that in the LRN group (P < 0.001, P < 0.001, respectively). CONCLUSION: Our results demonstrate the efficacy and safety of LPN in patients with T1 renal cell carcinoma. Although complication rates were similar in both groups, post-operative renal function was not different between the LPN-A and -B groups.

The Utility and Efficacy of Laparoscopic Radical Cystectomy in Patients with Muscle-Invasive Bladder Cancer at a Single Institution.

BACKGROUND: The aim of this study was to compare the surgical and oncological outcomes and complications of laparoscopic radical cystectomy (LRC) to those of open radical cystectomy (ORC) in patients with muscle-invasive bladder cancer (MIBC). METHODS: Our study focused on patients with histologically confirmed stage T2-T4a urothelial carcinoma of the bladder without distant metastases, who underwent LRC (LRC group) or ORC (ORC group). The primary endpoints in this study were the overall survival (OS) and recurrence-free survival (RFS) rates. RESULTS: In this study, 59 patients, 17 underwent LRC and 42 underwent ORC, were enrolled. The 2-year OS rate was 100% in the LRC group and 88.0% in the ORC group (p = 0.85). The 2-year RFS rate was 63.5% in the LRC group and 69.5% in the ORC group (p = 0.321). On multivariate analysis, the histological type, positive lymph node, and positive resection margin were significantly associated with the OS rates. CONCLUSIONS: This study suggested that LRC may achieve similar oncological outcomes and fewer perioperative complications and less blood loss compared to ORC. Therefore, LRC should be considered as one of the treatment options for patients with MIBC.