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.

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.

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.

Late genitourinary toxicity in salvage radiotherapy for prostate cancer after radical prostatectomy: impact of daily fraction doses.

OBJECTIVE: To evaluate the impact of daily fraction doses on late genitourinary (GU) toxicity after salvage radiotherapy (SRT) for prostate cancer. METHODS: This multi-institutional retrospective study included 212 patients who underwent SRT between 2008 and 2018. All patients received image-guided intensity-modulated SRT at a median dose of 67.2 Gy in 1.8-2.3 Gy/fraction. The cumulative rates of late grade ≥2 GU and gastrointestinal (GI) toxicities were compared using Gray's test, stratified by the ≤2.0 Gy/fraction (n = 137) and ≥2.1 Gy/fraction groups (n = 75), followed by multivariate analyses. The total dose was represented as an equivalent dose in 2-Gy fractions (EQD2) with α/ß = 3 Gy. RESULTS: After a median follow-up of 63 months, the cumulative rates of 5-year late grade ≥2 GU and GI toxicities were 14 and 2.5%, respectively. The cumulative rates of 5-year late grade ≥2 GU toxicity in the ≥2.1 Gy/fraction and ≤2.0 Gy/fraction groups were 22 and 10%, respectively (p = 0.020). In the multivariate analysis, ≥2.1 Gy/fraction was still associated with an increased risk of late grade ≥2 GU toxicity (hazard ratio, 2.37; 95% confidence interval, 1.12-4.99; p = 0.023), while the total dose was not significant. CONCLUSION: The present results showed that ≥2.1 Gy/fraction resulted in a higher incidence of late grade ≥2 GU toxicity in SRT. ADVANCES IN KNOWLEDGE: The impact of fraction doses on late GU toxicity after SRT remains unknown. The results suggest that higher fraction doses may increase the risk of late GU toxicity in SRT.

Successful treatment with enfortumab-vedotin of metastatic signet ring cell cancer expressing nectin-4 and originating from the bladder.

Introduction: As an aggressive adenocarcinoma phenotype, primary signet ring cell carcinoma of the urinary bladder is an extremely rare variant. The prognosis of metastatic signet ring cell carcinoma of the urinary bladder is extremely poor and the clinical course for its specific pathogenesis remains unelucidated. Case presentation: A 64-year-old Japanese male patient was diagnosed with invasive urothelial carcinoma with glandular differentiation of a signet ring cell-type with pT4aN0M0, and he was eventually diagnosed with metastatic signet ring cell carcinoma of the urinary bladder. He was initially responsive to systemic combination induction chemotherapy of S-1 and cisplatin followed by avelumab switch maintenance therapy; however, signet ring cell carcinoma of the urinary bladder relapse occurred in the pathological findings of a biopsy from the right thigh. Immunohistochemical analysis of this specimen identified strong positive staining for nectin-4 and, following enfortumab-vedotin treatment, the patient showed a good response. Conclusion: We thus describe a rare case of metastatic signet ring cell carcinoma of the urinary bladder with nectin-4 expression diagnosed by a biopsy of a metastatic site.

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.

Proton pump inhibitors and potassium competitive acid blockers decrease pembrolizumab efficacy in patients with metastatic urothelial carcinoma.

We elucidated the efficacy of gut microbiome-altering drugs on pembrolizumab efficacy in patients with metastatic urothelial carcinoma (mUC). Clinical data were analyzed retrospectively from 133 patients with mUC who received second-line pembrolizumab therapy between January 2018 and January 2021, following failed platinum-based chemotherapy. We evaluated the effects of gut microbiome-altering drugs (proton pump inhibitors [PPI]/potassium-competitive acid blockers [P-CAB], H2 blockers, antibiotics, non-steroidal anti-inflammatory drugs [NSAIDs], metformin, antipsychotics, steroids, and opioids), taken by patients within 30 days before/after pembrolizumab treatment, on progression-free survival (PFS) and overall survival (OS). Fifty-one patients received PPI/P-CAB (37/14, respectively); H2 blockers, 7; antibiotics, 35; NSAIDs, 22; antipsychotics, 8; metformin, 3; steroids, 11; and opioids, 29. Kaplan-Meier curves revealed PPI or P-CAB users showed shorter PFS than non-PPI-P-CAB users (p = 0.001, p = 0.005, respectively). Multivariate analysis highlighted PPI/P-CAB use as the only independent prognostic factor for disease progression (hazards ratio: 1.71, 95% confidence interval: 1.14-2.07, p = 0.010) but not death (p = 0.177). Proton pump inhibitors/potassium-competitive acid blockers may decrease the efficacy of pembrolizumab therapy for mUC, possibly via gut microbiome modulation.

Impact of radiation doses on clinical relapse of biochemically recurrent prostate cancer after prostatectomy.

The relationship between radiation doses and clinical relapse in patients receiving salvage radiotherapy (SRT) for biochemical recurrence (BCR) after radical prostatectomy (RP) remains unclear. We identified 292 eligible patients treated with SRT between 2005 and 2018 at 15 institutions. Clinical relapse-free survival (cRFS) between the ≥ 66 Gy (n = 226) and < 66 Gy groups (n = 66) were compared using the Log-rank test, followed by univariate and multivariate analyses and a subgroup analysis. After a median follow-up of 73 months, 6-year biochemical relapse-free survival, cRFS, cancer-specific survival, and overall survival rates were 58, 92, 98, and 94%, respectively. Six-year cRFS rates in the ≥ 66 Gy and < 66 Gy groups were 94 and 87%, respectively (p = 0.022). The multivariate analysis revealed that Gleason score ≥ 8, seminal vesicle involvement, PSA at BCR after RP ≥ 0.5 ng/ml, and a dose < 66 Gy correlated with clinical relapse (p = 0.015, 0.012, 0.024, and 0.0018, respectively). The subgroup analysis showed the consistent benefit of a dose ≥ 66 Gy in patients across most subgroups. Doses ≥ 66 Gy were found to significantly, albeit borderline, increase the risk of late grade ≥ 2 GU toxicity compared to doses < 66 Gy (14% vs. 3.2%, p = 0.055). This large multi-institutional retrospective study demonstrated that a higher SRT dose (≥ 66 Gy) resulted in superior cRFS.

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.

Combination of robot-assisted laparoscopic pyeloplasty for lower moiety ureteropelvic junction obstruction in a partial duplex system and percutaneous endoscopic surgery for renal calculi reusing the port for robotic pyeloplasty.

Introduction: Ureteropelvic junction obstruction is often associated with renal calculus formation. However, there is no report of using robot-assisted laparoscopic pyeloplasty combined with percutaneous endoscopic surgery for ureteropelvic junction obstruction and renal calculi in a partial duplex system. Case presentation: A 19-year-old female patient with lower moiety ureteropelvic junction obstruction and renal calculi in a partial duplex system was referred to our hospital because of left lumbar pain, left acute pyelonephritis, and an increase in left renal calculi during follow-up at the referral hospital. To prevent the complication of percutaneous nephrolithotripsy following pyeloplasty, robot-assisted laparoscopic pyeloplasty combined with percutaneous endoscopic surgery was performed. Two years after surgery, the patient reported no left lumbar pain. Conclusion: The combination of robot-assisted laparoscopic pyeloplasty and percutaneous endoscopic surgery can be proposed as a safe and less-invasive treatment option for ureteropelvic junction obstruction and renal calculi in a partial duplex system.

The Geriatric Nutritional Risk Index Predicts Prognosis in Japanese Patients with LATITUDE High-Risk Metastatic Hormone-Sensitive Prostate Cancer: A Multi-Center Study.

Malnutrition is associated with prognosis in cancer. The geriatric nutritional risk index (GNRI), based on the ratio of actual to ideal body weight and also serum albumin level, is a simple screening tool for assessing nutrition. We investigated the GNRI as a prognostic factor for oncological outcomes in patients with high-risk metastatic hormone-sensitive prostate cancer (mHSPC) using a Japanese multicenter cohort. This study included a total of 175 patients with LATITUDE high-risk mHSPC, of whom 102 had received androgen deprivation therapy (ADT) plus upfront abiraterone acetate, and 73 had received ADT plus bicalutamide (Bica), from 14 institutions associated with the Tokai Urologic Oncology Research Seminar. Patients were classified into GNRI-low (<98) or GNRI-high (≥98) groups. The GNRI was based on the body mass index and serum albumin level. Kaplan-Meier analysis revealed that the median overall survival (OS) of a GNRI-low group (median 33.7 months; 95% confidence interval [CI]: 26.2-not reached [NR]) was significantly worse than that of a GNRI-high group (median: NR; 95% CI: NR-NR; p < 0.001). Multivariate analysis identified Bica and low GNRI (<98) as independent prognostic factors for reduced times to both castration-resistant prostate cancer and OS, and, therefore, a poor prognosis. Our findings indicate the GNRI may be a practical prognostic indicator in the evaluation of survival outcomes in patients with LATITUDE high-risk mHSPC.

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.

A narrative review of peripheral blood parameters for urothelial carcinoma treated with systemic antitumor drugs.

Background and Objective: The prognosis of advanced urothelial carcinoma (aUC) is poor. To date, the gold standard of treatment for patients with aUC has been cisplatin-based chemotherapy. More recently, immune checkpoint inhibitors (ICIs) have been widely used for such patients, which has led to an improvement in their prognosis. In clinical practice, predicting the effectiveness of antitumor drugs or the prognosis of patients is important for making decisions on treatment strategies. Various parameters obtained from blood tests in the pre-ICI era have been adopted for patients in the ICI era. In this review, we summarize the parameters reflecting the status of aUC patients treated with ICIs based on current evidence. Methods: We conducted a literature search using PubMed and Google Scholar. The publications chosen were all peer-reviewed journals published over an unlimited time period. Key Content and Findings: Numerous inflammatory or nutritional parameters can be obtained from routine blood tests. These reflect malnutrition or systemic inflammation in patients with cancer. As in the pre-ICI era, these parameters are useful for predicting the effectiveness of ICIs and the prognosis of patients treated with ICIs. Conclusions: Various parameters are related to systemic inflammation and malnutrition, and are easily obtained from a routine blood test. Using these parameters from various studies as reference points is useful in making decisions on treatment for aUC.

Hemoglobin and neutrophil levels stratified according to International Metastatic Renal Cell Carcinoma Database Consortium risk predict the effectiveness of ipilimumab plus nivolumab in patients with advanced metastatic renal cell carcinoma.

OBJECTIVE: To identify biomarkers associated with the effectiveness of ipilimumab plus nivolumab against advanced metastatic renal cell carcinoma. METHODS: We retrospectively analyzed the data of 75 patients treated with ipilimumab plus nivolumab at seven hospitals between August 2018 and April 2021. Prognostic biomarkers were assessed prior to initiating treatment with ipilimumab plus nivolumab. Median overall survival and progression-free survival were examined using the Kaplan-Meier method. Univariate and multivariate analyses were performed to identify predictors of disease progression. The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk factors most important for predicting disease progression were determined using classification and regression tree analysis. RESULTS: Median overall survival and progression-free survival were longer in the intermediate IMDC risk group than in the poor IMDC risk group (overall: not reached vs. 18.3 months; progression-free: not reached vs. 13.5 months). The multivariate analysis identified poor IMDC risk as a risk factor for disease progression (hazard ratio 2.61, 95% confidence interval: 1.05-6.51). Based on the results of the classification and regression tree analysis, the cohort was divided into non-anemia, anemia + neutro-Low, and anemia + neutro-High groups. Median overall survival and progression-free survival were longer in the non-anemia and anemia + neutro-Low groups than in the anemia + neutro-High group (overall: not reached vs. 29.3 months vs. 4.3 months: progression-free: not reached vs. 29.0 months vs. 3.9 months). CONCLUSION: Hemoglobin and neutrophil levels may represent crucial biomarkers for predicting the effectiveness of ipilimumab plus nivolumab therapy in patients with renal cell carcinoma.