Efficacy and Safety of Immuno-Oncology Plus Tyrosine Kinase Inhibitors as Late-Line Combination Therapy for Patients with Advanced Renal Cell Carcinoma.

Background/Objectives: Immuno-oncology plus tyrosine kinase inhibitor (IO+TKI) combination therapy is an essential first-line therapy for advanced renal cell carcinoma (RCC). However, reports of its efficacy and safety as late-line therapy are lacking. This study aimed to examine the efficacy and safety of IO+TKI combination therapy as a late-line therapy for patients with RCC. Methods: We retrospectively examined 17 patients with RCC who received IO+TKI combination therapy as a second-line therapy or beyond (pembrolizumab plus axitinib, n = 10; avelumab plus axitinib, n = 5; nivolumab plus cabozantinib, n = 2). Results: The overall response and disease control rates of IO+TKI combination therapy were 29.4% and 64.7%, respectively. The median overall survival was not attained. Progression-free survival was 552 days, and 94.1% of patients (n = 16) experienced adverse effects (AEs) of any grade; moreover, 41.2% of patients (n = 7) experienced grade ≥ 3 immuno-related AEs. Conclusions: IO+TKI combination therapy may be a late-line therapy option for RCC.

Defining a learning curve for urology trainees to achieve renal access without complications in endoscopic combined intrarenal surgery.

OBJECTIVES: There is a lack of data on the number of surgeries required for endoscopic combined intrarenal surgery (ECIRS). Accordingly, we aimed to identify the learning curve for ECIRS performed by multiple surgeons. METHODS: We included 296 patients who underwent ECIRS at our university hospital between 2016 and 2021. A learning curve for percutaneous nephrolithotomy side was calculated considering urology-resident surgeons. The learning curve was retrospectively analyzed for surgical time, renal puncture time, stone-free rate, and complications and corrected for age, body mass index, stone size, computed tomography value, cumulative number of surgeries, and stone location. RESULTS: This study included cases performed by 32 surgeons, including 30 residents and 2 attending surgeons. The median number of surgeries performed by the residents and attending surgeons prior to this study was 4.5 and 90, respectively. The median number of surgical procedures performed during the training period was seven. The surgical time of the residents decreased as the number of cases increased, reaching a median surgical time of 111 min for the attending surgeons after 16.4 cases. Renal puncture time was achieved in 20.1 cases. Complications related to renal access were observed in 13.0% (34 patients), Clavien-Dindo grade II in 1.9% (5 patients), and grade III or higher in 0.8% (2 patients). Comparing the first to fifth cases with the 21st and subsequent cases, the complication rate improved from 35% to 13%. CONCLUSION: Our study demonstrated that ECIRS training provided 16-20 cases with a learning curve to achieve acceptable surgical outcomes.

Calcium phosphate controls nucleation and growth of calcium oxalate crystal phases in kidney stones.

Kidney stone disease is a serious disease due to the severe pain it causes, high morbidity, and high recurrence rate. Notably, calcium oxalate stones are the most common type of kidney stone. Calcium oxalate appears in two forms in kidney stones: the stable phase, monohydrate (COM), and the metastable phase, dihydrate (COD). Particularly, COM stones with concentric structures are hard and difficult to treat. However, the factor determining the growth of either COM or COD crystals in the urine, which is supersaturated for both phases, remains unclear. This study shows that calcium phosphate ingredients preferentially induce COM crystal nucleation and growth, by observing and analyzing kidney stones containing both COM and COD crystals. The forms of calcium phosphate are not limited to Randall's plaques (1-2 mm size aggregates, which contain calcium phosphate nanoparticles and proteins, and form in the renal papilla). For example, aggregates of strip-shaped calcium phosphate crystals and fields of dispersed calcium phosphate microcrystals (nano to micrometer order) also promote the growth of concentric COM structures. This suggests that patients who excrete urine with a higher quantity of calcium phosphate crystals may be more prone to forming hard and troublesome COM stones.

Differences in the clinical presentation of necrotizing fasciitis depending on the causative pathogen.

Necrotizing fasciitis is a fatal, soft tissue infection of the skin that requires prompt treatment. Historically, most cases have been attributed to group A beta-hemolytic Streptococcus infection. However, in recent years, other bacteria have been identified as causing necrotizing fasciitis. In the current study, we analyzed cases of necrotizing fasciitis and examined the significant differences in symptoms caused by pathogenic bacteria. We included 79 patients (43 males and 36 females, mean age 65.4 years) diagnosed with necrotizing fasciitis who visited our hospital between April 2004 and July 2023. The patients were classified into five groups based on the identified pathogen: group A beta-hemolytic Streptococcus; group B beta-hemolytic streptococcus; group G beta-hemolytic Streptococcus; mixed infection, including anaerobic bacteria; and Staphylococcus (S) aureus. The clinical characteristics of patients, including treatment duration and laboratory values, were analyzed. Group G beta-hemolytic Streptococcus was more common in older patients (Bonferroni method, p < 0.05). Patients with S. aureus tended to be hyperglycemic (Bonferroni method, p < 0.05), had a higher rate of bacteremia (Fisher's direct probability test, p < 0.05), and had a longer treatment duration than the other examined groups (Bonferroni method, p = 0.0132). Although the five groups did not differ in the mortality rate, overall survival was shorter in the mixed infection group than in the other groups (log-rank test, p < 0.05). The legs were the most common site of infection in the non-mixed infection group; in the mixed infection group, the pubic area was identified as the most common site of infection, accompanied by a poor prognosis. Collectively, these findings suggest that necrotizing fasciitis can be characterized by pathogenic bacteria and that these characteristics may inversely predict the pathogen of origin.

Prognostic impact of FAN score in patients receiving nivolumab plus ipilimumab for metastatic renal cell carcinoma.

FAN score is reportedly associated with prognostic outcomes in patients with urothelial carcinoma being treated with immune check point inhibitors. However, the prognostic impact of pre-treatment FAN score in patients with metastatic renal cell carcinoma (RCC) treated with nivolumab plus ipilimumab remains unclear. We retrospectively evaluated the association between pre-treatment FAN score and prognostic outcomes in 154 patients with metastatic RCC treated with nivolumab plus ipilimumab. The pre-treatment FAN score was '0' in 56 patients (36%), '1' in 60 patients (40%), '2' in 37 patients (24%) and '3' in one patient (1%). Progression-free survival was not significantly different between patients with different FAN scores, but second progression-free survival (PFS2), cancer-specific survival (CSS) and overall survival (OS) were significantly different. In multivariable Cox proportional hazard analyses, FAN score ≥ 2 was a significant predictor of poor PFS2 (vs. FAN score 0, HR: 2.43, 95% CI 1.21-4.87, P = 0.01), poor CSS (vs. FAN score 0, HR: 2.71, 95% CI 1.13-6.47, P = 0.02) and poor OS (vs. FAN score 0, HR: 2.42, 95% CI 1.11-5.25, P = 0.02). High pre-treatment FAN score could be a significant independent predictor of poor prognosis in patients receiving nivolumab plus ipilimumab for metastatic RCC.

Real-world data on efficacy/safety and economic impact of nivolumab administered every 2 and 4 weeks among Japanese patients.

AIM: A new treatment interval for nivolumab administration at 480 mg every 4 weeks, in addition to 240 mg every 2 weeks, was approved in Japan in 2020. Using model-based evaluation, it was speculated that the effects or safety of nivolumab do not differ between the two treatment intervals; however, real-world data on nivolumab efficacy, safety, and economic impact are lacking. Accordingly, we aimed to examine the effects of nivolumab treatment intervals (2 weeks vs. 4 weeks) in terms of efficacy, safety, and economic impact in Japanese patients with cancer. METHODS: We retrospectively analyzed 126 patients treated with nivolumab. The patients were divided into two groups depending on whether they received nivolumab at 240 mg every 2 weeks (2-week group) or 480 mg every 4 weeks (4-week group). RESULTS: Efficacy results found no significant difference between the 4- and 2-week groups considering median overall survival (p = 0.70) and median progression-free survival (p = 0.57). The incidence of any grade and ≥  grade 3 immune-related adverse events did not differ between the 4-week and 2-week groups (any grade, p = 0.13; ≥  grade 3, p = 0.36). Excluding drug costs, the 4-week group had significantly lower medical costs than the 2-week group (2-week vs. 4-week: mean, 94,659 JPY [679.0 USD] vs. 58,737 JPY [421.3 USD]; p < 0.05). CONCLUSION: Collectively, our findings suggest that nivolumab 480 mg every 4 weeks may be more effective than nivolumab 240 mg every 2 weeks in terms of economic impact.

The impact of crystal phase transition on the hardness and structure of kidney stones.

Calcium oxalate kidney stones, the most prevalent type of kidney stones, undergo a multi-step process of crystal nucleation, growth, aggregation, and secondary transition. The secondary transition has been rather overlooked, and thus, the effects on the disease and the underlying mechanism remain unclear. Here, we show, by periodic micro-CT images of human kidney stones in an ex vivo incubation experiment, that the growth of porous aggregates of calcium oxalate dihydrate (COD) crystals triggers the hardening of the kidney stones that causes difficulty in lithotripsy of kidney stone disease in the secondary transition. This hardening was caused by the internal nucleation and growth of precise calcium oxalate monohydrate (COM) crystals from isolated urine in which the calcium oxalate concentrations decreased by the growth of COD in closed grain boundaries of COD aggregate kidney stones. Reducing the calcium oxalate concentrations in urine is regarded as a typical approach for avoiding the recurrence. However, our results revealed that the decrease of the concentrations in closed microenvironments conversely promotes the transition of the COD aggregates into hard COM aggregates. We anticipate that the suppression of the secondary transition has the potential to manage the deterioration of kidney stone disease.

Japanese survey of perioperative complications and ureteral stricture after ureteroscopy with laser lithotripsy for upper urinary tract stones in multicenter collaborative study.

OBJECTIVES: This study aimed to investigate perioperative complications and the details of postoperative ureteral stricture after ureteroscopy with laser lithotripsy (URS-L) for upper urinary tract stones in Japan. METHODS: Patient data on intra- and postoperative complications after ureteroscopy using URS-L were retrospectively collected from multiple centers in Japan between April 2017 and March 2020 with the cooperation of the Japanese Society of Endourology and Robotics. Data included the number of patients undergoing URS-L, number and type of intra- and postoperative complications, and detailed characteristics of postoperative ureteral stricture. RESULTS: In total, 14 125 patients underwent URS-L over 3 years at 82 institutions. Annual URS-L numbers gradually increased from 4419 in 2017, to 4760 in 2018, and 4946 in 2019. The total complication rate was 10.5%, which was divided into intra-operative complications in 1.40% and postoperative complications in 9.18%. The annual incidences of intra- and postoperative complications were not significantly different from year to year (p = 0.314 and p = 0.112). Ureteral perforation, ureteral avulsion, and the intra-operative conversion rate were 1.35%, 0.03%, and 0.02%, respectively. Fever >38°C, septic shock, blood transfusion, and postoperative mortality were 7.44%, 0.81%, 0.07%, and 0.04%, respectively. Ureteral stricture occurred in 0.8% of cases. The median length of stricture site was 10.0 mm and the success rate of stricture treatment was 54.6%. CONCLUSION: Although URS-L utilization has increased in Japan, the annual complication rate has remained steady. Although URS-L is a useful and less invasive procedure, devastating complications can still occur.

Three-dimensional computed tomography-based resection process map for robot-assisted partial nephrectomy: propensity score matching of a single-center retrospective study.

BACKGROUND AND OBJECTIVES: We aimed to examine the effect of preoperative three-dimensional (3D) computed tomography (CT)-based resection process map (RPM) imaging on the outcomes of robot-assisted partial nephrectomy (RAPN). METHODS: We retrospectively analyzed 177 patients (RPM group, n = 92; non-RPM group, n = 85) who underwent this surgery between November 2012 and April 2022. Patient-specific contrast-enhanced CT images were used to construct an RPM, a 3D representation of the kidney showing the planned tumor resection and a 5 mm safety margin. Outcome analyses were performed using propensity score matching. The primary endpoint was the trifecta achievement rate. RESULTS: We extracted 90 cases. The trifecta achievement rate showed no significant differences between the RPM (73.3%) and non-RPM groups (73.3%). However, the RPM group had fewer Grade 3 and higher complications (0.0% vs. 13.3%, p = 0.026). The da Vinci Xi (OR 3.38, p = 0.016) and tumor diameter (OR 0.95, p = 0.013) were independent factors affecting trifecta achievement in multivariate analysis. Using RPM imaging was associated with the absence of Grade 3 and higher perioperative complications (OR 5.33, p = 0.036) in univariate analysis. CONCLUSIONS: Using preoperative 3D CT-based RPM images before RAPN may not affect trifecta achievement, but may reduce serious complication occurrence by providing detailed information on tumor resection.

Association of lung immune prognostic index with survival outcomes in patients with metastatic renal cell carcinoma treated with nivolumab plus ipilimumab.

OBJECTIVE: Lung immune prognostic index is based on derived neutrophil-to-lymphocyte ratio and lactate dehydrogenase level. Lung immune prognostic index has reported association with survival outcomes in patients with various malignancies undergoing treatment with immune checkpoint inhibitors. However, the prognostic impact of pre-treatment lung immune prognostic index in patients with metastatic renal cell carcinoma receiving nivolumab plus ipilimumab treatment remains unclear. This study examines the association between lung immune prognostic index and outcomes in this setting. METHODS: We retrospectively evaluated 156 patients with metastatic renal cell carcinoma treated with nivolumab plus ipilimumab at eight institutions. We assessed the associations between pre-treatment lung immune prognostic index and survival outcomes including progression-free survival, second progression-free survival (PFS2), cancer-specific survival and overall survival. RESULTS: Patients were classified into good (n = 84, 54%), intermediate (n = 52, 33%) and poor (n = 20, 13%) lung immune prognostic index groups. Progression-free survival did not significantly differ between lung immune prognostic index groups, but there was significant difference in PFS2, cancer-specific survival and overall survival. In multivariable Cox proportional hazard analyses, high pre-treatment lung immune prognostic index was a significant predictor of poor PFS2 (vs. good group, intermediate group: P = 0.01 and poor group: P = 0.04) and poor overall survival (vs. good group, intermediate group: P = 0.01 and poor group: P < 0.01). Moreover, the patients with poor lung immune prognostic index had significantly poorer cancer-specific survival than those with good LIPI (P < 0.01). CONCLUSIONS: High pre-treatment LIPI is suggested by our results to be a significant independent predictor of poor prognosis in patients receiving nivolumab plus ipilimumab for metastatic renal cell carcinoma.

Phagocytosis model of calcium oxalate monohydrate crystals generated using human induced pluripotent stem cell-derived macrophages.

Macrophages play a role in nephrolithiasis, offering the possibility of developing macrophage-mediated preventive therapies. To establish a system for screening drugs that could prevent the formation of kidney stones, we aimed to develop a model using human induced pluripotent stem cell (iPSC)-derived macrophages to study phagocytosis of calcium oxalate monohydrate (COM) crystals. Human iPSCs (201B7) were cultured. CD14+ monocytes were recovered using a stepwise process that involved the use of growth factors and cytokines. These cells were then allowed to differentiate into M1 and M2 macrophages. The macrophages were co-cultured with COM crystals and used in the phagocytosis experiments. Live cell imaging and polarized light observation via super-resolution microscopy were used to visualize phagocytosis. Localization of phagocytosed COM crystals was observed using transmission electron microscopy. Intracellular fluorescence intensity was measured using imaging cytometry to quantify phagocytosis. Human iPSCs successfully differentiated into M1 and M2 macrophages. M1 macrophages adhered to the culture plate and moved COM crystals from the periphery to cell center over time, whereas M2 macrophages did not adhere to the culture plate and actively phagocytosed the surrounding COM crystals. Fluorescence assessment over a 24-h period showed that M2 macrophages exhibited higher intracellular fluorescence intensity (5.65-times higher than that of M1 macrophages at 4.5 h) and maintained this advantage for 18 h. This study revealed that human iPSC-derived macrophages have the ability to phagocytose COM crystals, presenting a new approach for studying urinary stone formation and highlighting the potential of iPSC-derived macrophages as a tool to screen nephrolithiasis-related drugs.

Urothelial carcinoma occurring in a defunctionalized bladder after urinary diversion due to the bladder exstrophy-epispadias complex.

Introduction: The bladder exstrophy-epispadias complex is a rare congenital disease. Urothelial carcinomas rarely occur in patients with this disease, and there have been few reports on its treatment. Case presentation: We report the case of a 44-year-old man with a hemorrhage from the external urethral meatus. He was diagnosed with bladder exstrophy-epispadias complex and underwent urinary diversion with substitution cystoplasty and Mitrofanoff appendicovesicostomy. Because computed tomography and magnetic resonance imaging suggested invasive bladder carcinoma in the defunctionalized bladder, we performed a cystectomy. The patient was diagnosed with urothelial carcinoma with glandular differentiation. One month after the surgery, nivolumab adjuvant chemotherapy was administered. The patient showed no signs of recurrence or metastasis after the treatment. Conclusion: This is the first case of adjuvant nivolumab therapy for urothelial carcinoma with the bladder exstrophy-epispadias complex.

Comparison of Percutaneous Renal Access Between Robot-Assisted Fluoroscopy Guidance Using the Bi-Plane Method and Ultrasound Guidance: A Multicenter Randomized Control Benchtop Study.

Purpose: To evaluate the efficacy of supine percutaneous renal access by robot-assisted (RA) fluoroscopy and ultrasound (US) guidance in terms of procedural outcomes and surgeon workload. Methods: We conducted a multicenter, randomized, controlled benchtop study involving 32 urologists using a renal phantom model. RA puncture was performed using the developed version of automated needle targeting with X-ray (ANT-X), which determines the direction of the needle. US puncture was performed under US guidance. The primary endpoint was the single-puncture success rate, and the secondary outcomes were the procedural time for each step, time of fluoroscopic exposure, and workload assessment. Results: The single-puncture success rates were 90.6% and 56.3% for RA and US punctures, respectively (p < 0.01). In RA puncture, the median device setup time was 120 seconds longer, the median total procedural time was 100 seconds longer, the median time of fluoroscopic exposure was 40 seconds longer, the median needle puncture time was 17 seconds shorter, and the distance from the target sphere was 1 cm shorter than those in US puncture (all p < 0.01). The mental and physical task workload, effort required by the surgeons, frustration felt by the surgeons, and overall National Aeronautics and Space Administration Task Load Index scores were lower in the RA puncture group than in the US puncture group (p = 0.01, p = 0.046, p < 0.01, p = 0.021, and p ≤ 0.01, respectively). Conclusions: RA puncture using ANT-X, which can also be used for puncture in the supine position, offers advantages over renal puncture in terms of accuracy and surgical workload.

Efficacy of Robot-Assisted Ureteroureterostomy in Patients with Complex Ureteral Stricture after Ureteroscopic Lithotripsy.

BACKGROUND: Ureteral stricture (US) postureteroscopic lithotripsy (URSL) has emerged as a severe complication with the widespread use of laser technology. Furthermore, managing a complex US is challenging. Therefore, this study evaluated the efficacy of robot-assisted ureteroureterostomy (RAUU) in addressing US post-URSL and analyzed the pathology of transected ureteral tissues to identify the risk factors for US. METHODS: we conducted a prospective cohort study on patients who underwent RAUU for URSL-induced US from April 2021 to May 2023. RESULTS: A total of 14 patients with a mean age of 49.8 years were included in this study. The mean stricture length on radiography was 22.66 ± 7.38 mm. Nine (64.2%) patients had experienced failure with previous interventions. The overall success rate was 92.9%, both clinically and radiographically, without major complications, at a mean follow-up of 12.8 months. The pathological findings revealed microcalcifications and a loss of ureteral mucosa in 57.1% and 28.6% of patients, respectively. CONCLUSIONS: The RAUU technique shows promise as a viable option for US post-URSL in appropriately selected patients despite severe pathological changes in the ureter. Therefore, the migration of microcalcifications to the site of ureteral perforation may be a significant factor contributing to US development.

Eosinophil may be a predictor of immune-related adverse events induced by different immune checkpoint inhibitor types: A retrospective multidisciplinary study.

BACKGROUND: Immune checkpoint inhibitors (ICIs) can cause severe immune-related adverse events (irAEs). However, biomarkers for irAEs common to different types of ICIs and cancers have not been reported. This study examined whether eosinophils can be used as a predictor of irAEs. METHODS: Six hundred fourteen patients with cancer (esophageal, gastric, head and neck, lung, melanoma, renal cell, urothelial, and other cancer) received anti-PD-1, anti-PD-L1, or anti-CTLA-4 plus anti-PD-1 therapy. The patients were divided into two groups depending on whether they experienced irAEs (irAE group) or not (non-irAE group). Eosinophils were examined before the two-course treatment. RESULTS: Patients in the irAE group who received anti-PD-1 or anti-CTLA-4 plus anti-PD-1 therapy had higher eosinophils before the two-course treatment than those in the non-irAE group (p < 0.05). The eosinophils in the anti-PD-L1 therapy group tended to increase in the irAE group. Furthermore, eosinophils in gastric, head and neck, lung, melanoma, renal, and urothelial cancers were significantly higher in the irAE group than in the non-irAE group (p < 0.05). The optimal cutoff value for eosinophils against irAEs was 3.0% (area under the curve = 0.668). In multivariate analyses, eosinophils of ≥3.0% were an independent factor for irAEs (odds ratio: 2.57, 95% CI: 1.79-3.67). CONCLUSION: An increased eosinophil before the two-course treatment may be a predictor of irAEs in various cancers treated with different ICIs.

Postoperative Bladder Neck to Pubic Symphysis Ratio Predictive for De Novo Overactive Bladder after Robot-Assisted Radical Prostatectomy.

BACKGROUND: The aim was to investigate the incidence and clinical predictive factors of de novo overactive bladder (OAB) after robot-assisted radical prostatectomy (RARP), including a Retzius-sparing (RS) approach, in the same period at a single institution. METHODS: Of a total of 113 patients with localized prostate cancer, 81 received conventional RARP (CON-RARP) and 32 received RS-RARP at our institution. The basic characteristics data of patients and self-assessment questionnaires, including IPSS and OABSS, were obtained preoperatively and 1, 3, and 6 months after RARP. In addition, a retrospective biomarker analysis was also performed of predictive clinical parameters obtained from cystography that included a postoperative bladder neck to pubic symphysis (BNPS) ratio. RESULTS: Patients' basic characteristics were similar between CON-RARP and RS-RARP groups. With respect to the surgical procedure, anastomosing time was found to be significantly longer for patients in the RS-RARP compared to the CON-RARP group (p < 0.01). Compared to the CON-RARP group, the RS-RARP group showed a significantly lower postoperative BNPS and aspect ratio (p < 0.001). The incidence of de novo OAB in patients of the CON-RARP group was greater than for those in the RS-RARP group (40.7% CON-RARP vs. 25.0% RS-RARP), though this was not significant. Regarding the emergence of de novo OAB, the following were revealed in univariate analysis to be independent prognostic factors: age > 64 years (hazards ratio [HR]: 4.32, 95% confidence interval [CI]: 1.51-12.3), postoperative BNPS ratio > 0.44 (HR: 8.7, 95% CI: 6.43-54.5), postoperative aspect ratio > 1.18 (HR: 3.36, 95% CI: 1.49-7.61). Additionally, multivariate analysis identified a sole significant prognostic factor: postoperative BNPS ratio > 0.44 (HR: 13.3, 95% CI: 4.33-41.1). CONCLUSION: Our findings indicate that the postoperative BNPS ratio may be a practical predictive indicator of the emergence of de novo OAB after RARP.

Quality of life after urinary stone surgery based on Japanese Wisconsin Stone Quality of Life questionnaire: multicenter analysis from SMART study group.

We aimed to evaluate the impact of surgical treatment for urinary stones on perioperative health-related quality of life (HRQOL) using the Japanese Wisconsin Stone Quality of Life questionnaire (J-WISQOL), an HRQOL measure designed for patients with urinary stones. This study prospectively enrolled 123 patients with urinary stones who visited three academic hospitals for stone treatment. The participants completed the J-WISQOL within 4 weeks before and after the urinary stone treatment. Treatments included shock wave lithotripsy (SWL), ureteroscopy lithotripsy, and endoscopic combined intrarenal surgery. J-WISQOL was assessed for age, stone size and location, type of treatment, stone-free status, postoperative ureteral stent placement, hospital stay, and complications in all patients. Patients with stones in the ureter had significantly greater social impact D1 and disease impact D3 than those with stones in the kidney. In a comparison of pre- and postoperative J-WISQOL, patients without postoperative ureteral stent placement scored significantly higher on social impact D1 and disease impact D3. Patients with shorter hospital stays had significantly higher social impact D1 and disease impact D3 (p < 0.001) than those with longer hospital stays. SWL significantly improved the total score, social impact D1, and disease impact D3 compared with other treatments. Perioperative HRQOL in patients with urinary stones is particularly affected by the type of treatment, ureteral stent placement, and hospital stay, which should be considered in surgical selection and patient decision-making.

Application of ultrasound imaging in the treatment of urinary tract stones.

Urinary tract stones are a common clinical condition that affect millions of individuals worldwide. The management of these stones has evolved significantly over the past 70 years, and ultrasound imaging has emerged as a valuable tool for diagnosis, treatment planning, and follow-up. This review aims to provide an overview of the application of ultrasound imaging in the treatment of urinary tract stones, highlighting its advantages, limitations, and current advancements in the field.

Elevated eosinophils proportion as predictor of immune-related adverse events after ipilimumab and nivolumab treatment of advanced and metastatic renal cell carcinoma.

OBJECTIVES: Ipilimumab and nivolumab treatment against advanced and metastatic renal cell carcinoma (RCC) causes severe and lethal immune-related adverse events (irAEs). Predicting irAEs might improve clinical outcomes, however no practical biomarkers exist. This study examined whether eosinophils could be effective biomarkers for ≥grade 2 irAEs in RCC. METHODS: We retrospectively analyzed 75 patients with RCC treated with ipilimumab and nivolumab between August 2018 and March 2021 in a multicenter study. Eosinophils were examined before and 2 weeks after treatment, and immediately after irAEs development. The optimal cut-off value for ≥grade 2 irAEs was determined by a receiver operating characteristic (ROC) curve. Univariate and multivariate analyses were undertaken to identify predictors of ≥grade 2 irAEs. RESULTS: Two weeks after treatment, eosinophils were significantly upregulated in patients who had experienced ≥grade 2 irAEs than in those who had not experienced irAEs (mean, 5.7% vs. 3.2%; p < 0.05). The optimal cut-off value for eosinophils against ≥grade 2 irAEs was 3.0% (area under the curve = 0.69). In multivariate analyses, an eosinophil level ≥ 3.0% was a risk factor for ≥grade 2 irAEs (odds ratio 4.18, 95% confidence interval 1.16-15.1). The eosinophil level 2 weeks after treatment was upregulated by the onset of any type of irAEs including endocrine, gastrointestinal, pulmonary and skin disorders. CONCLUSIONS: An increased eosinophil level 2 weeks after treatment might be an effective biomarker for ≥grade 2 irAEs in patients with RCC treated with ipilimumab and nivolumab.