The efficacy of second-line tyrosine kinase inhibitor for patients with metastatic non-clear cell renal cell carcinoma following first-line immune-oncology combination therapy.

PURPOSE: Metastatic non-clear cell renal cell carcinoma (nccRCC) is a heterogeneous disease with a poor prognosis and is treated with immunotherapy (IO)-based combinations according to the clear cell renal cell carcinoma. Tyrosine-kinase inhibitors (TKIs), such as cabozantinib and axitinib, are commonly used as the 2nd line therapy after 1st line IO combination therapy, but their efficacy as 2nd line TKI therapy for nccRCC is unknown. In this study, we performed a retrospective multicenter analysis of nccRCC patients who were previously treated with IO combination therapy and received 2nd line TKIs. METHODS: Among 254 patients enrolled in the Japanese multicenter retrospective study, 52 patients with nccRCC histology who received second-line TKIs were included in this study. Progression-free survival and overall survival (OS) from 2nd line TKIs were analyzed by log-rank test and Cox-proportional hazard model. Objective response rate (ORR) of 2nd line TKIs were analyzed. RESULTS: The 1-year PFS and OS rates were 25.0% (95% CI = 13.1-36.8) and 63.8% (95% CI, 48.0-75.9), respectively. No patients had a complete response, 11 had a partial response, and 18 had stable disease. ORR was 21.1%. IMDC poor risk and sunitinib as the 2nd line therapy were significantly associated with poor PFS. CONCLUSION: The 2nd-line TKI was effective for a small group of nccRCC patients previously treated with IO combination therapy, although this study was retrospectively analyzed with a small number of cases.

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.

Effect of nephrostomy sheath size on renal pelvic pressure during endoscopic combined intrarenal surgery: artificial kidney model study.

BACKGROUND: This study aimed to evaluate the intrarenal pelvic pressure in endoscopic combined intrarenal surgery using an artificial kidney model. METHODS: An artificial kidney model was created using the Urovac evacuator™. Four sizes of nephrostomy sheaths (MIP-L: 25/26 Fr, MIP-M: 16.5/17.5 Fr, MIP-S: 11/12 Fr, MIP-XS: 8.5/9.5 Fr) and two sizes of ureteral access sheaths (12/14 Fr and 10/12 Fr) were installed into the model. For each combination of nephrostomy and ureteral access sheath, renal pelvic pressure was measured with and without insertion of the retrograde flexible ureteroscope. Irrigation from the nephroscope was adjusted to 40-160 mmHg using an automatic irrigation device, and the irrigation of the ureteroscope was by spontaneous dripping at 80 cmH2O. Conditions were measured six times, and the renal pelvic pressure was compared in different conditions. RESULTS: Without ureteroscope insertion through the ureteral access sheath, the renal pelvic pressure never exceeded 30 mmHg. Meanwhile, when the ureteroscope was inserted, the renal pelvic pressure increased as the nephrostomy sheath and ureteral access sheath became narrower and as the irrigation pressure increased. Intrarenal pelvic pressure exceeded 30 mmHg when the irrigation pressure was increased in 12/14 Fr ureteral access sheath when MIP-XS was used, and in 10/12 Fr ureteral access sheath when MIP-XS and MIP-S were used. CONCLUSIONS: The use of a thin nephrostomy sheath in endoscopic combined intrarenal surgery can lead to increased intrarenal pelvic pressure. Although our results are from an artificial kidney model, special care is suggested to be required when using a retrograde flexible ureteroscope simultaneously in treatment of patients.

Poor performance status is a risk factor for higher detection of Gram positive coccus in stone-related pyelonephritis.

INTRODUCTION: We aimed to investigate the detection rate of causative organisms in stone-related pyelonephritis and to compare their distribution according to patient backgrounds. METHODS: We retrospectively identified patients with stone-related pyelonephritis. Clinical data were collected between November 2012 and August 2020 at Wakayama Medical University Hospital, including on patient backgrounds and causative organisms. Patients were categorized by Eastern Cooperative Oncology Group performance status (PS) as the good PS group (0, 1) and the poor PS group (2-4). Bacteria were divided into Gram-positive cocci (GPC) or non-GPC groups and logistic regression analysis was used to examine factors that predict detection of GPC. RESULTS: Seventy-nine patients had stone-related pyelonephritis, 54 (68.4 %) in the good PS group and 25 (31.6 %) in the poor PS group. In the good PS group, Escherichia coli (67 %) was followed by Klebsiella species (9 %), while in the poor PS group, Escherichia coli (20 %) was followed by Enterococci and Staphylococci (12 %). GPC detection rate was significantly higher in the poor PS group than in the good PS group (40.0 % vs 14.8 %, p = 0.016), and multivariate logistic regression analysis showed that poor PS was an independent factor predicting detection of GPC (OR = 6.54, p = 0.02). CONCLUSIONS: The distribution of the causative organisms in stone pyelonephritis was similar to that in common complicated urinary tract infections. Poor PS may be an independent predictor of GPC detection in patients with stone pyelonephritis.

Local extension findings on MRI compensate for the ability of pathological staging to predict oncological outcome.

BACKGROUND: We investigated whether local extension findings on preoperative MRI and excisional pathology are associated with positive surgical margin and biochemical recurrence after robot-assisted radical prostatectomy. METHODS: We identified 704 of our patients that underwent robot-assisted radical prostatectomy between 2012 and 2020, and extracted the 326 patients who had preoperative MRI scans and a radiologist reading. These patients were classified into groups according to the presence of local extension on MRI and pathological findings: ≤ cT2pT2 (195 cases), ≤ cT2pT3 (55 cases), cT3pT2 (31 cases), and cT3pT3 (45 cases). We compared positive surgical margin and biochemical recurrence between them. RESULTS: Median age was 69 years, positive surgical margin rate was 20.2%, and five-year biochemical recurrence rate was 20.3%. Of the 226 patients without local invasion on excisional pathology, those with local extension on MRI (cT3pT2) had relatively higher positive surgical margin rate (29.0% vs. 14.4%, p = 0.05) and significantly higher five-year biochemical recurrence rate (25.8% vs. 9.3%, p = 0.01) than those without local extension on MRI (≤ cT2pT2). Similarly, among the 100 patients with local extension on excisional pathology, those with cT3pT3 had relatively higher positive surgical margin (37.8% vs. 21.8%, p = 0.08) and significantly higher five-year biochemical recurrence (53.3% vs. 29.3%, p = 0.01) than those with ≤ cT2pT3. In multivariate analysis, local extension on MRI was an independent predictor of biochemical recurrence (OR 2.1, 95%CI 1.1-3.9, p = 0.01). CONCLUSIONS: Local extension on MRI is a prognostic factor independent of pathological stage. The use of MRI may complement the prognostic value of excisional pathology of prostate cancer.

Myosteatosis as a novel predictor of new-onset diabetes mellitus after kidney transplantation.

OBJECTIVES: We evaluate the effect of myosteatosis on new-onset diabetes mellitus after kidney transplantation. METHODS: Consecutive patients who had renal transplant between 2006 and 2021 were reviewed, and 219 patients were finally included. Psoas muscle index was used to evaluate sarcopenia and average total psoas density (calculated by computed tomography before surgery) for myosteatosis. We used Cox proportional regression analyses in investigation of whether skeletal muscle depletion before surgery inclusive of sarcopenia and myosteatosis is a new additional predictor of new-onset diabetes mellitus. RESULTS: Median recipient age and body mass index were 45 years and 21.1 kg/m2 , respectively, and 123 patients (56%) were male. Preoperative impaired glucose tolerance was present in 58 patients (27%) and new-onset diabetes mellitus in 30 patients (14%), with median psoas muscle index of 6 cm2 /m2 and average total psoas density of 41 Hounsfield Unit. In multivariate analysis, significant risk factors were body mass index ≥25 kg/m2 (p < 0.01), impaired glucose tolerance (p < 0.01), and average total psoas density < 41.9 Hounsfield Unit (p = 0.03). New-onset diabetes mellitus had incidence rates of 3.7% without risk factors, 10% with a single risk factor, 33% with two, and 60% with three. Patients with new-onset diabetes mellitus were effectively stratified by the number of risk factors (p < 0.01). CONCLUSIONS: Myosteatosis could be a new risk factor used to predict new-onset diabetes mellitus.

In vitro comparison of simulated intrapelvic pressure in an artificial kidney model during retrograde intrarenal surgery among various single-use ureteroscopes.

OBJECTIVES: This study compares intrapelvic pressure (IPP) during retrograde intrarenal surgery with various single-use flexible ureteroscopes (f-URS) in an artificial kidney model. METHODS: We created an artificial kidney model with a pressure sensor using a bladder evacuation device. The model was completely closed and the only backflow was on the side of the ureteroscope inside the ureteral access sheath (UAS). We tested five single-use f-URSs (LithoVue, Wiscope, PU3022A, PU3033A, and AXIS) with six different types of UAS (9.5/11.5-14/16 Fr). Using the automatic irrigation system, 30 s of irrigation was performed at various pressures (40-180 mmHg) and steady-state IPP was recorded. IPP was compared between the five single-use f-URSs. IPP cutoff value was determined at 30 mmHg. The diameter of the endoscope tip and the curved and shaft parts were also measured and recorded. RESULTS: The diameters of all parts were significantly different between single-use f-URSs. The maximum IPP tended to be higher in ureteroscopes with larger diameters of the proximal parts (curved part/shaft part). In LithoVue and Uscope PU3022A f-URSs, the maximum IPP did not exceed 30 mmHg when UAS ≥12/14 Fr was used. In AXIS and Wiscope f-URSs, it did not exceed the cutoff value when the UAS ≥11/13 Fr was used. In Uscope PU3033A f-URS, it did not exceed 30 mmHg when the UAS ≥10/12 Fr was used. CONCLUSIONS: Maximum IPP tended to be higher in f-URSs with larger diameters of the proximal part and the appropriate size of the UAS differed between various single-use f-URSs.

Pharmacotherapy for patients with calcium oxalate stones and abnormal urine chemistry: A systematic review and meta-analysis for the Japanese Clinical Practice Guidelines for the Management of Urinary Stones, Third Edition.

We performed a systematic review and meta-analysis to evaluate the benefits and harms of pharmacotherapies for patients with calcium oxalate stones and abnormal urine chemistry. This article is a modified and detailed version of the commentary on Clinical Question 10 described in the Japanese Clinical Practice Guidelines for the Management of Urinary Stones, Third Edition. PubMed and Ichushi Web were searched through August 2020 for articles on pharmacotherapies for calcium oxalate stones (thiazides, citrate preparations, uric acid production inhibitors, and magnesium preparations). Two reviewers independently selected randomized controlled trials reporting reduction of stone recurrence and adverse drug reactions as outcomes and performed data extraction and quality assessment. Meta-analyses with random effects models and rating of the strength of evidence were performed. Pharmacotherapies were shown to significantly reduce stone recurrence (risk ratio 0.47, 95% confidence interval 0.35-0.63). Meanwhile, the pharmacotherapies increased adverse drug reactions leading to study dropout (risk ratio 2.51, 95% confidence interval 1.09-5.75) and adverse drug reactions/adverse events (risk ratio 1.95, 95% confidence interval 1.07-3.56). The reported adverse drug reactions were, however, mainly minor and did not frequently require discontinuation of medication (2%-16%). The strengths of evidence for both outcomes were rated as moderate, because the risk of bias, indirectness, inconsistency, imprecision, and publication bias were all serious except for one item. The overall strength of evidence across outcomes was therefore determined to be moderate. These results support the conditional recommendation to initiate pharmacotherapies for patients with calcium oxalate stones and abnormal urine chemistry.

Prognostic outcomes in patients with metastatic renal cell carcinoma receiving second-line treatment with tyrosine kinase inhibitor following first-line immune-oncology combination therapy.

OBJECTIVES: This study aimed to assess the prognostic outcomes in mRCC patients receiving second-line TKI following first-line IO combination therapy. METHODS: This study retrospectively included 243 mRCC patients receiving second-line TKI after first-line IO combination therapy: nivolumab plus ipilimumab (n = 189, IO-IO group) and either pembrolizumab plus axitinib or avelumab plus axitinib (n = 54, IO-TKI group). Oncological outcomes between the two groups were compared, and prognostication systems were developed for these patients. RESULTS: In the IO-IO and IO-TKI groups, the objective response rates to second-line TKI were 34.4% and 25.9% (p = 0.26), the median PFS periods were 9.7 and 7.1 months (p = 0.79), and the median OS periods after the introduction of second-line TKI were 23.1 and 33.5 months (p = 0.93), respectively. Among the several factors examined, non-CCRCC, high CRP, and low albumin levels were identified as independent predictors of both poor PFS and OS by multivariate analyses. It was possible to precisely classify the patients into 3 risk groups regarding both PFS and OS according to the positive numbers of the independent prognostic factors. Furthermore, the c-indices of this study were superior to those of previous systems as follows: 0.75, 0.64, and 0.61 for PFS prediction and 0.76, 0.70, and 0.65 for OS prediction by the present, IMDC, and MSKCC systems, respectively. CONCLUSIONS: There were no significant differences in the prognostic outcomes after introducing second-line TKI between the IO-IO and IO-TKI groups, and the histopathology, CRP and albumin levels had independent impacts on the prognosis in mRCC patients receiving second-line TKI, irrespective of first-line IO combination therapies.

Prognostic significance of pre-treatment albumin-bilirubin grade in metastatic urothelial carcinoma receiving pembrolizumab.

BACKGROUND: Pre-treatment albumin-bilirubin grade is a useful biomarker for predicting prognosis in patients receiving immune checkpoint inhibitors for advanced malignancies. We evaluated the prognostic impact of pre-treatment albumin-bilirubin grade in patients receiving pembrolizumab for metastatic urothelial carcinoma. METHODS: In this multicenter retrospective study, we calculated pre-treatment albumin-bilirubin scores of 96 patients who received pembrolizumab for metastatic urothelial carcinoma between January 2018 and March 2022. Patients were classified according to albumin-bilirubin grade. Progression-free survival and cancer-specific survival were compared between the groups. To evaluate the prognostic impact of pre-treatment albumin-bilirubin grade, we also performed Cox proportional regression analyses for progression-free survival and cancer-specific survival. RESULTS: The median pre-treatment albumin bilirubin score was -2.52 (quartile: -2.76 to -2.10), and albumin-bilirubin grade was grade 1 in 37 patients (39%), grade 2a in 30 patients (31%), 2b in 22 patients (23%) and grade 3 in 7 patients (7%). The median progression-free survival and cancer-specific survival were 2 and 7 months, respectively. Progression-free survival and cancer-specific survival were significantly different between the albumin-bilirubin grade groups (P < 0.01 and P < 0.01, respectively) and prognosis became poorer as albumin-bilirubin grade increased. High albumin-bilirubin grade was shown in multivariable Cox proportional analyses to be independently associated with both poor progression-free survival and poor cancer-specific survival. CONCLUSIONS: High pre-treatment albumin-bilirubin grade could be a significant independent predictor of poor prognosis in patients receiving pembrolizumab for advanced urothelial carcinoma.

Comprehensive endoscopic management of impacted ureteral stones: Literature review and expert opinions.

Treatment of urolithiasis, a benign disease, requires high efficacy and safety. Endoscopic treatment of impacted ureteral stones remains a challenging procedure for urologists, despite recent remarkable advances in surgical technology in treatment of urolithiasis. The success rate of endoscopic treatment in patients with impacted stones is reported to be lower than that in patients with nonimpacted stones. Moreover, the presence of stone impaction is associated with high rates of intraoperative and postoperative complications. The best management for patients with impacted ureteral stones should therefore be devised based on the latest knowledge and techniques. The present review focuses on the preoperative prediction of stone impaction, the safest and most effective endoscopic surgical procedures, and the most appropriate management for postoperative ureteral strictures. We overview comprehensive endoscopic management for impacted ureteral stones based on literature review and expert opinions.

Myosteatosis as a novel predictor of urinary incontinence after robot-assisted radical prostatectomy.

OBJECTIVES: To evaluate the impact of sarcopenia and myosteatosis on urinary incontinence after prostatectomy. METHODS: We retrospectively reviewed consecutive patients who underwent robot-assisted radical prostatectomy without nerve sparing between December 2012 and March 2019. Psoas muscle index and average total psoas density, which were measured on preoperative computed tomography images at level L3, were used to evaluate sarcopenia and myosteatosis, respectively. In addition, several magnetic resonance imaging variables associated with pelvic muscles, the urethra and the prostate were measured. Urinary continence was defined as non-use or use of just one incontinence pad per day. Logistic regression analyses aimed to identify the predictors of urinary incontinence 3 and 12 months after surgery. RESULTS: Overall, 121 patients were included in the analysis. The incidence rates of urinary incontinence 3 and 12 months after surgery were 42% (51/121 cases) and 16% (19/121 cases), respectively. Logistic multivariable analysis showed that low average total psoas density was the only significant independent predictor of urinary incontinence 3 months after surgery (P < 0.01), and low obturator internus muscle thickness (P = 0.01), short membranous urethral length (P = 0.01) and low average total psoas density (P < 0.01) were significant independent predictors of urinary incontinence 12 months after surgery. By contrast, psoas muscle index was not statistically associated with urinary incontinence after surgery. CONCLUSIONS: Myosteatosis (low average total psoas density) could be a novel predictor of urinary incontinence after robot-assisted radical prostatectomy.

[Usefulness of Immunostaining Scoring for Predicting Response to Single-Agent Nivolumab in Patients with Metastatic Renal Cell Carcinoma].

Although several biomarkers have been identified to predict prognosis in renal cell carcinoma (RCC), there are no evidence-based biomarkers to predict the response to immune checkpoint inhibitors. In this study, we focused on lymphocytes and tumor cells in the tumor microenvironment and investigated whether immunostaining scoring could predict the best overall response. We evaluated 32 patients with metastatic RCC (mRCC) who were treated with nivolumab monotherapy between August 2016 and July 2020. We performed immunostaining for CD8 T cells, TIA-1, PD-L1, and HLA class 1 in RCC tissues and assigned a score with a maximum of 4 points each, which we defined as histological score. The best overall response of nivolumab was observed in 4 patients (12.5%) with complete response (CR), 10 patients (31.3%) with partial response (PR), 5 patients (15.6%) with stable disease (SD), and 13 patients (40.6%) with progressive disease (PD). There was no significant difference in patient background between the CR＋PR＋SD group (19 patients) and the PD group (13 patients), but CD8 T cells were significantly higher and TIA-1 positive cells tended to be higher in the CR＋PR＋SD group (CD8 T cell : p＝0.03, TIA-1 : p＝0.07, PD-L1 : p＝0.67, HLA class 1 : p＝1.00). In univariate analysis, histological score ≥3 tended to contribute to the best overall response of nivolumab (p＝0.05). There was no significant difference in overall survival or cancer-specific survival after nivolumab administration between the two groups of patients with histological score ≥3 and those with histological score ＜3. In conclusion, immunostaining scoring based on CD8 T cells may be able to predict the efficacy of single-agent nivolumab in patients with mRCC.

Inverse planning in high-dose rate brachytherapy improves quality of life of prostate cancer patients compared with forward planning.

OBJECTIVES: To understand differences in quality of life outcomes between cases with forward planning and cases with inverse planning, we examine patients undergoing high-dose rate brachytherapy combined with external beam radiotherapy for localized prostate cancer. METHODS: We prospectively identified 283 patients with localized prostate cancer and divided them into forward planning and inverse planning groups. We extracted data on doses to the prostate, rectum and urethra that could potentially affect quality of life. We also evaluated quality of life using the Japanese version of Medical Outcome Study 8-Items Short Form Health Survey and Expanded Prostate Cancer Index Composite at pre-treatment and at 3, 6, 12 and 24 months after treatment. Wilcoxon signed rank test and Bonferroni correction were used to analyze the irradiation dose and any change in quality of life. RESULTS: Doses to the prostate and rectum were not significantly different between the two groups. Notably, however, doses to the urethra were significantly lower in the inverse planning group than in the forward planning group. Patients in the forward planning group had significantly poorer physical component summary scores at 3 months according to survey results. In Expanded Prostate Cancer Index Composite, patients in the forward planning group had statistically significant poorer urinary, bowel and sexual scores than those in the inverse planning group. Quality of life related to decline in sexual function was significantly reduced in the inverse planning group. CONCLUSIONS: Inverse planning in high-dose rate brachytherapy could significantly improve quality of life of patients with prostate cancer.

Impact of preoperative sarcopenia and myosteatosis on prognosis after radical cystectomy in patients with bladder cancer.

OBJECTIVE: To evaluate the prognostic impact of sarcopenia and myosteatosis on survival after radical cystectomy for bladder cancer. METHODS: We retrospectively reviewed consecutive patients who underwent radical cystectomy for bladder cancer between 2010 and 2019, and 123 patients were finally included in this single-center study. Pretreatment computed tomography images at the L3 level were used to calculate skeletal muscle index and skeletal muscle density. Sarcopenia and myosteatosis were diagnosed according to the gender-specific cutoff values of skeletal muscle index and skeletal muscle density used in a previous study. We compared overall survival and cancer-specific survival between patients with and without sarcopenia/myosteatosis. We also performed Cox proportional regression analyses to identify the predictors of overall survival and cancer-specific survival. RESULTS: The median patient age was 74 years, and 20 patients (16%) were female. Thirty-eight patients (31%) died from bladder cancer and 13 (11%) died from other causes. The patients with sarcopenia (n = 48, 39%) and those with myosteatosis (n = 101, 82%) had significantly lower overall survival and cancer-specific survival rates than those without sarcopenia and those without myosteatosis, respectively. In multivariable analysis, in addition to the number of pathological risk factors, both sarcopenia (P < 0.01) and myosteatosis (P = 0.04) were independent significant predictors of poor cancer-specific survival. CONCLUSIONS: In our experience, sarcopenia and myosteatosis are independent predictors of poor cancer-specific survival in patients undergoing radical cystectomy for bladder cancer. Sarcopenia is also associated with poor overall survival.

Ureteroscopy-assisted puncture for ultrasonography-guided renal access significantly improves overall treatment outcomes in endoscopic combined intrarenal surgery.

OBJECTIVES: To assess the impact and availability of ureteroscopy-assisted puncture for percutaneous renal access during ultrasonography-guided miniaturized (mini)-endoscopic combined intrarenal surgery for large volume renal and/or proximal ureteral stones. METHODS: We conducted a multi-institutional retrospective cohort study for urolithiasis treatment. Data from a total of 313 patients who underwent mini-endoscopic combined intrarenal surgery to treat renal and/or ureteral stones between January 2016 and April 2020 were collected. We compared the outcomes between ultrasonography-guided mini-endoscopic combined intrarenal surgery with and without ureteroscopy-assisted puncture (ureteroscopy-assisted puncture(+) group [n = 126] and ureteroscopy-assisted puncture(-) group [n = 187] group, respectively). The primary outcome was requirement for additional surgical intervention. Secondary outcomes were stone-free rate, complications and total procedure, fluoroscopy, hospital stay, and postoperative ureteral stent placement durations. RESULTS: The ureteroscopy-assisted puncture(+) group had a lower additional surgical intervention rate and a higher stone-free rate immediately after and 3 months after surgery than the ureteroscopy-assisted puncture(-) group (5.6% vs 19.7%, P < 0.001; 82.5% vs 65.8%, P = 0.001; 59.5% vs 44.6%, P = 0.011). The median total procedure, fluoroscopy, and postoperative ureteral stent placement durations were 18 min, 3 min, and 5 days shorter, respectively, in the ureteroscopy-assisted puncture(+) group. Multivariate analyses showed that ureteroscopy-assisted puncture was associated with a decreased risk of additional surgical intervention (odds ratio 0.31, P = 0.011) and postoperative infection (odds ratio 0.34, P = 0.003) and decreased total procedure (estimate = -11 min; P = 0.011), fluoroscopy (estimate = -3 min; P = 0.034), and postoperative ureteral stent placement (estimate = -8 days; P = 0.011) durations. Female patients and those with smaller stone volumes or without hydronephrosis were identified as ideal ureteroscopy-assisted puncture candidates. CONCLUSIONS: Ureteroscopy-assisted puncture during mini-endoscopic combined intrarenal surgery could provide favorable surgical outcomes, especially in female patients without collecting system obstruction.

Predictive and sensitive biomarkers for thyroid dysfunctions during treatment with immune-checkpoint inhibitors.

Immune-related adverse events (irAEs) are often seen during immune-checkpoint inhibitor (ICI) treatment of various malignancies. Endocrine irAEs including thyroid dysfunctions are the most common irAEs, but their biomarkers remain unclear. In order to identify individuals who are susceptible to thyroid irAE for earlier diagnosis and appropriate follow-up, the current study is aimed to investigate biomarkers of thyroid irAE. Herein, patients with advanced malignant diseases who received ICIs treatment were prospectively studied. Clinical and laboratory examination, thyroid function, and autoantibodies were evaluated at baseline, and every 4 wk after first treatment with ICIs. Cytokines/chemokines were measured at baseline and at 4 wk. In vivo effects of ICIs on experimental autoimmune thyroiditis were evaluated. Twenty-six patients with malignant diseases who received ICIs treatment were enrolled in the study. Patients were divided into two groups: those who developed thyroid irAE, and those without irAEs. Comparing the two groups, early increase (≤4 wk) in serum thyroglobulin (Tg) levels and thyroid autoantibodies was seen in thyroid irAE (P < .05). Notably, higher levels of serum IL-1ß, IL-2, and GM-CSF at baseline, and early decrease of IL-8, G-CSF, and MCP-1 were significantly associated in the development of thyroid irAE (P < .05). In vivo effects of anti-PD-1 antibody on deterioration of mice experimental thyroiditis were seen. In conclusion, early change in Tg, thyroid autoimmunity, and cytokine levels might indicate development of thyroid irAE. Pre-existing thyroid autoimmunity might be involved with the development of thyroid irAE. Potential application of these factors as surrogate biomarkers for tumor therapy was indicated.

Three-dimensional mean stone density measurement is superior for predicting extracorporeal shock wave lithotripsy success.

OBJECTIVES: The objective of the present study was to investigate the usefulness of three-dimensional images of stones to measure mean stone density for predicting the outcome of shock wave lithotripsy. METHODS: We retrospectively identified 239 patients who underwent shock wave lithotripsy with pretreatment non-contrast computed tomography. We automatically measured the mean stone density of three-dimensional images of stones using a high-functional viewer. For comparison, mean stone density was also measured by two previously reported techniques using both the abdominal windows and the bone windows on the axial slice at the level of the largest diameter of the stone. We compared the outcome predictive power after the first treatment with outcomes according to measurement by four other methods. We also carried out logistic regression analysis, including mean stone density measured by three-dimensional images. RESULTS: The single treatment success rate was 48.5%. The effect size (14.148) of the mean stone density measured by three-dimensional images was higher than those of the other four manual methods. In addition, the area under the curve (0.6330) of the mean stone density measured by three-dimensional images was significantly higher than those of the other methods. Increasing stone volume (P = 0.002) and increasing mean stone density measured by three-dimensional images (P = 0.023) were significant independent predictors of the treatment outcome on multivariate analysis. CONCLUSIONS: This is the first study to compare the predictive powers for shock wave lithotripsy outcome of various mean stone density measuring methods. There is an indication that mean stone density automatically measured by three-dimensional images of stones is more useful than other measuring methods for predicting outcomes of shock wave lithotripsy.

Recurrent stone-forming patients have high visceral fat ratio based on computed tomography images compared to first-time stone-forming patients.

OBJECTIVES: To compare various fat parameters based on computed tomography images between recurrent stone-forming patients and patients forming stones for the first time. METHODS: Included in the present study were 300 patients with upper urinary tract calculi who had undergone active stone removal in our hospital. Using pretreatment computed tomography images, we measured visceral fat area and volume, subcutaneous fat area and volume, visceral fat area ratio and visceral fat volume ratio. We compared patient backgrounds and these fat parameters between those who recurrently formed stones and those who formed stones for the first time. We also performed logistic regression analysis to identify factors that contribute to severe stones. RESULTS: A total of 148 (49.3%) patients were recurrent stone-forming patients. Recurrent stone-forming patients were statistically significantly younger (P < 0.01) and there were more male patients (P < 0.01). In addition, visceral fat area ratio and visceral fat volume ratio in recurrent stone-forming patients were significantly higher than those in first-time stone-forming patients (P = 0.03 and P = 0.01, respectively). On the other hand, there was no significant difference in visceral fat area (P = 0.32), subcutaneous fat area (P = 0.36), visceral fat volume (P = 0.38) or subcutaneous fat volume (P = 0.23). Receiver operating characteristics analysis showed that area under the curve of visceral fat volume ratio (0.583) for recurrent stones was larger than that of visceral fat area ratio (0.571). In multivariate analysis, increasing visceral fat volume ratio was an independent significant predictor of recurrent stones (P = 0.04). CONCLUSIONS: Recurrent stone-forming patients have high visceral fat ratios compared to first-time stone-forming patients, shown here for the first time.