Fourth national Japanese antimicrobial susceptibility pattern surveillance program: Bacterial isolates from patients with complicated urinary tract infections.

INTRODUCTION: Antimicrobial susceptibility patterns of bacterial pathogens isolated from patients with complicated urinary tract infections were analyzed using the national surveillance data, comprising 793 bacterial strains from eight clinically relevant species. MATERIALS AND METHODS: Data were collected for the fourth national surveillance project from July 2020 to December 2021 by the Japanese Society of Chemotherapy, the Japanese Association for Infectious Disease, and the Japanese Society of Clinical Microbiology. Surveillance was supervised with the cooperation of 43 medical institutions throughout Japan. RESULTS: Fluoroquinolone required a minimum inhibitory concentration (MIC) of 2-64 mg/L to inhibit the 330 tested Escherichia coli strains. The proportion of levofloxacin-resistant E. coli strains increased from 28.6% in 2008 to 29.6% in 2011, 38.5% in 2015, and 44.5% in 2021. The proportion of levofloxacin-resistant strains of Pseudomonas aeruginosa also increased from previous survey results, showing a continuing downward trend. Conversely, the proportion of levofloxacin-resistant strains of Enterococcus faecalis decreased relative to previous reports. Neither multidrug-resistant P. aeruginosa nor carbapenem-resistant Enterobacteriaceae were detected. For methicillin-resistant Staphylococcus aureus (MRSA), the proportion of vancomycin-susceptible strains (MIC of 2 µg/mL) decreased from 14.7% to 7.7%. DISCUSSION: Bacterial strains that produced extended-spectrum ß-lactamase included E. coli (82/330 strains, 24.8%), Klebsiella pneumoniae (11/68 strains, 16.2%), and Proteus mirabilis (4/26 strains, 15.4%). As compared to previous surveillance reports, these strains showed an increase in proportion over the years.

Risk classification system using the detailed positive surgical margin status for predicting biochemical recurrence after robot-assisted radical prostatectomy.

AIM: This study aimed to evaluate the risk classification system using the detailed positive surgical margin (PSM) status to predict biochemical recurrence (BCR) after robot-assisted radical prostatectomy (RARP). METHODS: We retrospectively analyzed 427 patients who underwent RARP between January 2016 and March 2020. We investigated risk factors for BCR using univariate and multivariate Cox proportional hazard regression models. The biochemical recurrence-free survival (BRFS) rate was assessed using the Kaplan-Meier method. RESULTS: The median follow-up period was 43.4 months and 99 patients developed BCR. In the multivariate analysis, maximum PSM length > 5.0 mm and the International Society of Urological Pathology grade group (ISUP GG) at the PSM ≥3 were predictive factors for BCR in patients with a PSM. In the multivariate analysis, these factors were also independent predictive factors in the overall study population, including patients without a PSM. We classified the patients into four groups using these factors and found that the 1-year BRFS rates in the negative surgical margin (NSM) group, low-risk group (PSM and neither factor), intermediate-risk group (either factor), and high-risk group (both factors) were 94.9%, 94.5%, 83.1%, and 52.9%, respectively. The low-risk group showed similar BRFS to the NSM group (p = 0.985), while the high-risk group had significantly worse BRFS than the other groups (p < 0.001). CONCLUSION: Maximum PSM length > 5.0 mm and ISUP GG at the PSM ≥3 were independent predictive factors for BCR after RARP. Risk classification for BCR using these factors is considered to be useful and might help urologists decide on additional treatment after RARP.

Enzalutamide versus Abiraterone Plus Prednisolone for Nonmetastatic Castration-Resistant Prostate Cancer: A Sub-Analysis from the ENABLE Study for PCa.

Enzalutamide (ENZ) and abiraterone plus prednisolone (ABI) can improve the survival of patients with castration-resistant prostate cancer (CRPC). However, the agent that is more effective against nonmetastatic CRPC remains unclear. To evaluate the agent that can be used as the first-line treatment for CRPC, an investigator-initiated, multicenter, randomized controlled trial (ENABLE Study for PCa) including both metastatic and nonmetastatic CRPC was conducted in Japan. The prostate-specific antigen (PSA) response rate, overall survival, some essential survival endpoints, and safety of patients with nonmetastatic CRPC were also analyzed. In this subanalysis, 15 and 26 patients in the ENZ and ABI arms, respectively, presented with nonmetastatic CRPC. There was no significant difference in terms of the PSA response rate between the ENZ and ABI arms (80% and 64%, respectively; p = 0.3048). The overall survival did not significantly differ between the two arms (HR: 0.68; 95% CI: 0.22-2.14, p = 0.5260). No significant differences were observed in terms of radiographic progression-free survival and cancer-specific survival between the ENZ and ABI arms (HR: 0.81; 95% CI: 0.35-1.84; p = 0.6056 and HR: 0.72; 95% CI: 0.19-2.73; p = 0.6443, respectively). Only four and six patients in the ENZ and ABI arms, respectively, had ≥grade 3 adverse events. ABI and ENZ had similar efficacy and safety profiles in patients with nonmetastatic CRPC.

Significance of timing of therapeutic line on effectiveness of nivolumab for metastatic renal cell carcinoma.

Objectives: This study aimed to clarify the significance of therapeutic timing on the effectiveness of nivolumab for treating metastatic renal cell carcinoma. Marterials and methods: Fifty-eight patients with metastatic renal cell carcinoma treated with nivolumab monotherapy were retrospectively studied. Patients who were treated with nivolumab as second-line therapy were included in the second-line group, while the others were included in the later-line group. The clinicopathological characteristics, effects of nivolumab, and prognoses of these groups were compared. Results: Twenty and thirty-eight patients were included in the second-line and later-line groups, respectively. There were no significant differences in the distribution of International Metastatic Renal Cell Carcinoma Database Consotium risk and other clinicopathological characteristics between the 2 groups. The proportion of patients whose objective best response was progressive disease in the second-line group was significantly lower than that in the later-line group (15% vs. 50%, p = 0.0090). The 50% progression-free survival with nivolumab in the second-line group was significantly better than that in the later-line group (not reached and 5 months, p = 0.0018). Multivariate analysis showed that the second-line setting was an independent predictive factor for better progression-free survival (p = 0.0028, hazard ratio = 0.108). The 50% overall survival after starting nivolumab in the second-line and later-line groups was not reached and 27.8 months, respectively (p = 0.2652). Conclusions: The therapeutic efficacy of nivolumab as second-line therapy is expected to be better than that of later therapy.

Clinical factors for tumor response, progression, and survival in nivolumab for advanced renal cell carcinoma in the SNiP-RCC study.

BACKGROUND: This study is part of the SNPs in Nivolumab PD-1 inhibitor for RCC (SNiP-RCC). Here we aimed to reveal clinical factors for tumor response, progression, and survival in nivolumab for advanced clear cell renal cell carcinoma (RCC) in Japanese patients. METHODS: We included patients from 23 institutions in Japan. We evaluated the objective response, radiographic progression-free survival (PFS), overall survival (OS), and treatment-related grade ≥ 3 (serious adverse events [SAEs]). RESULTS: We included 222 patients. The median age was 69 years (interquartile range 62-74 years), and 71% of the patients were male. Pancreas metastasis, lung metastases, prior cytokine therapy, and SAEs, were associated with objective response. The median PFS was 18 months. Liver metastases (hazard ratio [HR], 1.61), age ≥ 75 (HR, 0.48), previous resection of primary sites (HR, 0.47), and SAEs (HR, 0.47) were independent prognostic factors for PFS. Karnofsky Performance Status <70 (HR, 2.90), high platelets (HR, 4.48), previous resection of primary sites (HR, 0.23), and pathological grade (HR, 0.19 for grade 2 and HR, 0.12 for grade 3) were independent prognostic factors for OS. SAEs were reported in 45 (20.3%) cases. In the group of patients with prior nephrectomy, SAEs were associated with objective response, PFS, and OS. CONCLUSION: The SNiP-RCC study identified clinical parameters correlated with treatment outcomes in Japanese patients with priorly treated advanced clear cell RCC undergoing nivolumab monotherapy.

Effect of genetic polymorphisms on outcomes following nivolumab for advanced renal cell carcinoma in the SNiP-RCC trial.

BACKGROUND: Anti-PD-1 antibodies are widely used for cancer treatment including advanced renal cell carcinoma (RCC). However, their therapeutic and adverse effects vary among patients. This study aimed to identify genetic markers that predict outcome after nivolumab anti-PD-1 antibody treatment for advanced RCC. METHODS: This study was registered on the website of the University Hospital Medical Information Network (protocol ID, UMIN000037739). Patient enrollment was conducted at 23 institutions in Japan between August 19, 2019, and September 30, 2020. Patient follow-up ended on March 31, 2021. Patients were treated with nivolumab for advanced clear cell RCC. A genome-wide association study was performed in the development set, while genotyping of target regions in the validation set was undertaken. Single nucleotide polymorphisms (SNPs) in genes of interest CD274, PDCD1LG2 and PDCD1 were genotyped in the combined set. The primary endpoint was the association of SNPs with objective response following nivolumab treatment. As secondary endpoints, the associations of SNPs with radiographic progression-free survival (rPFS) and treatment-related grade ≥ 3 adverse events (AEs) were evaluated. RESULTS: A genome-wide association study followed by a validation study identified that SNPs in FARP1 (rs643896 and rs685736) were associated with objective response and rPFS but not AEs following nivolumab treatment. Furthermore, SNPs in PDCD1LG2 (rs822339 and rs1411262) were associated with objective response, rPFS, and AEs following nivolumab treatment. Genetic risk category determined according to the number of risk alleles in SNPs (rs643896 in FARP1 and rs4527932 in PDCD1LG2) excellently predicted objective response and rPFS in nivolumab treatment. CONCLUSION: This study revealed that SNPs in FARP1 and PDCD1LG2 were correlated with outcome in nivolumab treatment. The use of these SNPs may be beneficial in selecting appropriate treatment for individual patients and may contribute to personalized medicine.

Impact of low and high body mass index on predicting therapeutic efficacy and prognosis in patients with metastatic renal cell carcinoma treated with first-line tyrosine kinase inhibitors.

OBJECTIVE: To evaluate the significance of both low and high body mass index (BMI) as a biomarker in first-line tyrosine kinase inhibitors (TKIs) for metastatic renal cell carcinoma (mRCC). METHODS: The oncological outcome of 235 patients with mRCC treated with TKI from 2007 to 2018 was reviewed retrospectively. All patients received first-line TKI as therapy. We analyzed the relationship between BMI (low and high) and disease control rate. The primary outcome was progression free survival and overall survival, and the association between BMI and survival prognosis was evaluated. RESULTS: The median BMI was 22.5 kg/m2 , and 25 patients (10.7%) had a low BMI (<18.5 kg/m2 ), 158 patients (67.2%) had a normal BMI (18.5-25 kg/m2 ), and 52 patients (22.1%) had a high BMI (≥ 25 kg/m2 ). Patients in the low BMI group had a significantly lower disease control rate, whereas patients in the high BMI group had a significantly higher disease control rate (p = 0.002 and p = 0.030, respectively). A log-rank test showed prognosis to be significantly poorer in the low BMI group and to be significantly better in the high BMI group than that in the normal BMI group. Multivariable Cox regression analysis showed that low BMI was an independent indicator of poor prognosis, whereas high BMI was an independent indicator of favorable prognosis. CONCLUSION: We showed the impact of both low and high BMI on predicting therapeutic efficacy and prognosis in mRCC patients treated with TKI.

The effect of aging on the repeated-dose liver micronucleus assay using diethylnitrosamine.

BACKGROUND: The repeated-dose liver micronucleus (RDLMN) assay has been well-developed and applied because of its simplicity and the ease of integration into general toxicity studies which is the preferred method from the 3R's point of view. In this assay, we observed micronucleated hepatocytes which accumulated during a rather long-term dosing period. When considering integration into general toxicity studies, the effects of age of the animals used in the micronucleus assay becomes a major issue. The effect of age on the micronucleus induction rate has been reported in bone marrow micronucleus assays, and it is considered that the decrease in cell proliferation rate due to aging is the cause of the decrease in sensitivity. A decrease in sensitivity due to aging was also reported in a liver micronucleus assay using clofibrate and the cause is considered to be a decrease in hepatocyte proliferation activity due to aging. However, no actual decrease in hepatocyte proliferation rate due to aging has been reported. In addition, there are no reports, so far, on whether similar effects of aging appear when other substances were administered. To investigate the effects of aging in the RDLMN assay, this study focused on the effects of 14-day repeated administration of DEN, a well-known genotoxic hepatocarcinogen with the hepatocyte toxicity which should cause an elevation of cell proliferation rate as a reflective regeneration. RESULTS: The liver micronuclei induced by DEN were equivalent between the two age groups (i.e., six and eight weeks of age at the start of dosing). In the histopathological examination for the liver, single cell necrosis, karyomegaly, and increased mitosis were observed in the hepatocytes, and the frequency and severity were increased dose-dependently. Ki-67 immunohistochemical analysis which can detect all cells in the cell cycle other than those in the G0 phase revealed dose-dependent increase of cell proliferation activity, and the difference between ages was not observed. CONCLUSION: The effect of aging on the RDLMN assay could not be recognized when DEN was administered for 14 days in rats. Meanwhile, it was supported by the histopathological examination and Ki-67 immunohistochemical analysis that such an effect of aging was masked by the compensatory hepatocyte proliferation which was induced by the hepatocyte toxicity of DEN.

Impact of modified Glasgow prognostic score on predicting prognosis and modification of risk model for patients with metastatic renal cell carcinoma treated with first line tyrosine kinase inhibitor.

INTRODUCTION AND OBJECTIVES: Intermediate risk group of the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria is thought to consist of patients with different prognoses. This study investigated the impact of a pretreated modified Glasgow prognostic score (mGPS), which is defined on the basis of the pretreated serum albumin and C-reactive protein level, on predicting the prognosis of patients with metastatic renal cell carcinoma (mRCC) and its usefulness for the re-stratification of patients into a more improved risk model. MATERIALS AND METHODS: One hundred ninety-six mRCC patients treated with first-line tyrosine kinase inhibitor (TKI) were retrospectively investigated. All patients were classified into either a high-mGPS or a low-mGPS group on the basis of mGPS score upon starting systemic therapy, the overall survival (OS) and cancer specific survival (CSS) rates in each group were compared. We use decision curve analysis and calculate C-index based on OS and CSS to compare IMDC+mGPS model and IMDC model. RESULTS: The categories of favorable, intermediate, and poor risk groups in the IMDC model were assessed in 32, 113, and 51 cases, respectively. The low- and high-mGPS groups consisted of 149 and 47 cases. The median OS in the high- and low-mGPS groups were 38.4 months and 5.6 months, and their median CSSs were 41.0 months and 5.6 months, respectively (P < 0.0001). Multivariate analysis showed that a high mGPS, multiple metastatic organs, and hypercalcemia were independent predictive factors for a worse OS (P = 0.0260). Next, we divided the intermediate risk group into two subgroups using the mGPS score. The OS and CSS for the high-mGPS subgroup were significantly worse than those for the low-mGPS one (P = 0.0024, median OS: 21.0 months and 33.7 months, P = 0.0007, median CSS: 21.0 months and 39.8 months), and there was no significant difference in OS between the high-mGPS subgroup in the intermediate risk group and poor risk group (P = 0.2250). The value of C-index based on OS at IMDC and IMDC+mGPS model were 0.6771 and 0.6967, and those based on CSS were 0.6850 and 0.7080, respectively. In decision curve analysis to evaluate the clinical net benefit using the IMDC+mGPS model compared to the IMDC model, there was no significant difference between the two groups. CONCLUSION: mGPS is useful for establishing a more improved prognostic model that is able to stratify mRCC patients treated with first-line TKI.

Enzalutamide Versus Abiraterone plus Prednisolone Before Chemotherapy for Castration-resistant Prostate Cancer: A Multicenter Randomized Controlled Trial.

Background: Enzalutamide (ENZ) and abiraterone plus prednisolone (ABI) improve survival in castration-resistant prostate cancer (CRPC). However, which agent is better for patients with CRPC remains unclear. Objective: To evaluate whether ENZ or ABI is better as first-line treatment for CRPC. Design setting and participants: An investigator-initiated, multicenter, randomized controlled trial was conducted in Japan. The study enrolled 203 patients with CRPC before chemotherapy between February 20, 2015, and July 31, 2019. Patients were randomly assigned 1:1 to the ENZ or ABI arm. Outcome measurements and statistical analysis: The primary endpoint was time to prostate-specific antigen (PSA) progression. Secondary endpoints included the PSA response rate (≥50% decline from baseline), overall survival, and safety. A log-rank test was used for comparison of survival analyses between arms. Results and limitations: After randomization, 92 patients in each arm were treated and analyzed. Time to PSA progression did not significantly differ between the arms (median 21.2 mo for ENZ and 11.9 mo for ABI; hazard ratio [HR] 0.81, 95% confidence interval [CI] 0.51-1.27; p = 0.1732). There was a significant difference in the PSA response rate between the arms (72% for ENZ and 57% for ABI; p = 0.0425). There was no significant difference in overall survival (median 32.9 mo for ENZA and 35.5 mo for ABI; HR 1.17, 95% CI 0.72-1.88; p = 0.5290). Grade ≥3 adverse events were observed in 11% of patients in the ENZA arm and 21% in the ABI arm (p = 0.1044). Conclusions: ENZ did not show any survival benefit in comparison to ABI, but showed a better PSA response rate with a low rate of severe adverse events in CRPC. Patient summary: Results from our study suggest that use of enzalutamide before abiraterone may have potential clinical benefits for patients with castration-resistant prostate cancer.

Prognostic model of upfront cytoreductive nephrectomy in patients with metastatic renal cell carcinoma treated with immune checkpoint inhibitors and/or targeted agents.

INTRODUCTION AND OBJECTIVES: The aim of this study was to investigate prognostic factors and to establish a prognostic model using them for upfront cytoreductive nephrectomy (CN) in patients with metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitor (ICI) and/or tyrosine kinase inhibitor (TKI). MATERIALS AND METHODS: Two hundred eleven patients who were diagnosed as mRCC at initial diagnosis and were treated with TKI and/or ICI were classified into 2 groups: those undergoing CN (upfront CN group, 117 cases) and those who initially underwent systemic therapy (non-upfront CN group, 94 cases). In the upfront CN group, the patients' background and overall survival (OS) were compared with those in the other two groups, and prognostic factors were analyzed. A prognostic model of the upfront CN group was established. RESULTS: The median of the observation period for the upfront CN group was 25 months. The rates of patients with clear cell histology, with a Karnofsky performance status (KPS) of ≥ 80%, with a single metastatic organ, with a normal pretreated C-reactive protein level, and with an intermediate risk according to the International mRCC Database Consortium (IMDC) model were significantly higher than those in the non-upfront CN group (87.2% and 30.9%, p < 0.0001; 92.3% and 77.7%, p = 0.0025; 41.9% and 24.5%, p = 0.0080; 47.9% and 13.8%, p < 0.0001; 66.7% and 45.7%, p = 0.0023, respectively). The 50% OS in the upfront CN group was 33.1 months, significantly better than that in the non-upfront CN group (11.1 months, p < 0.0001), and these results were consistent regardless of their prognostic risk level. Multivariate analysis showed that multiple metastatic organs and a KPS of < 80% were independent predictive factors for OS (hazard ratio: 1.653 and 2.995, p = 0.0339 and 0.0054, respectively). Using these two parameters to stratify the upfront CN group, the 50% OSs in cases with no risk factors, in those with one factor, and in those with two factors were 43.4 months, 29.1 months, and 7.7 months, respectively (p < 0.0001). CONCLUSION: The upfront CN group was able to be stratified by our prognostic model into three subgroups with different prognoses. This model can provide useful information for making decisions in consideration of upfront CN in patients with mRCC.

Comparison of surgical outcomes and split renal function between laparoscopic and robot-assisted partial nephrectomy: a propensity score-matched analysis.

PURPOSE: The objective of this study was to compare perioperative outcomes and total and split renal function between laparoscopic partial nephrectomy (LPN) and robot-assisted partial nephrectomy (RAPN). Predictive risk factors of preservation of operated renal function were also assessed. METHODS: We retrospectively analyzed 173 patients who underwent LPN (n = 84) or RAPN (n = 89) between 2010 and 2020. After propensity score matching (1:1), perioperative outcomes and total and split renal function were assessed. Logistic regression analysis was used to evaluate predictive risk factors of preservation of operated renal function. Trifecta criteria were defined as negative surgical margins, warm ischemia time (WIT) < 25 min, and no complications more than Clavien-Dindo grade II within 4 weeks after surgery. Split renal function was evaluated by mercaptoacetyltriglycine renal scan. RESULTS: After propensity score matching, 42 patients were allocated to each group. RAPN was associated with significantly shorter WIT (RAPN vs LPN: 12 vs 22 min; p < 0.0001) and higher trifecta achievement rate (93.3 vs 64.2%; p < 0.0001). Other perioperative outcomes and total and split renal function were not significantly different between LPN and RAPN. The R.E.N.A.L. nephrometry score (RNS) was a predictive risk factor of preservation of operated renal function in the multivariable logistic regression analysis (odds ratio 1.68, 95% confidence interval 1.29-2.20, p < 0.0001). CONCLUSIONS: RAPN improved WIT and trifecta achievement rate, but it did not improve the preservation of operated renal function, for which RNS was found to be a strong predictive risk factor.

CD44 Is Involved in Sunitinib Resistance and Poor Progression-free Survival After Sunitinib Treatment of Renal Cell Carcinoma.

BACKGROUND/AIM: Sunitinib continues to be administered as a first-line therapeutic agent in metastatic renal cell carcinoma (mRCC). This study aimed to examine the role of CD44 in sunitinib resistance and as a predictive marker in mRCC. MATERIALS AND METHODS: We analyzed the effect of CD44 knockdown on sunitinib resistance in RCC cell lines using WST-1 assays. CD44 expression in mRCC patients treated with first-line sunitinib was determined by immunohistochemistry. We validated the findings of this study by in silico analysis. RESULTS: CD44 knockdown increased sensitivity to sunitinib. Immunohistochemical analysis revealed that 19 (34.5%) of 55 mRCC cases were positive for CD44. CD44-positive cases were associated with poor progression-free survival (PFS) after first-line sunitinib treatment. In the JAVELIN 101 study, high CD44 expression was significantly associated with poor PFS after sunitinib but not after avelumab + axitinib therapy. CONCLUSION: CD44 is involved in sunitinib resistance and may be a promising marker for sunitinib treatment in mRCC.

P53 Is Involved in Sunitinib Resistance and Poor Progression-free Survival After Sunitinib Treatment of Renal Cell Carcinoma.

BACKGROUND/AIM: Sunitinib continues to be administered as a first-line therapeutic agent in metastatic renal cell carcinoma (mRCC). This study examined the potential role of p53 in sunitinib resistance and as a predictive marker in mRCC. MATERIALS AND METHODS: We analysed the effects of p53 knockout on sunitinib resistance. p53 expression in 53 mRCC patients receiving first-line sunitinib was determined immunohistochemically. We performed in silico analysis to examine the predictive value of p53 in mRCC. RESULTS: WST-1 assays showed that p53 knockout decreased sensitivity to sunitinib. Sunitinib and nutlin-3 together suppressed cell growth. Immunohistochemistry revealed 11 p53-positive cases among 53 patients with mRCC. Kaplan-Meier analysis showed that p53-positive cases tended to be associated with poor progression-free survival (PFS) after first-line sunitinib treatment. In the JAVELIN 101 study, TP53 mutation was significantly associated with poor PFS after sunitinib treatment. CONCLUSION: p53 may be involved in sunitinib resistance and represent a valuable marker for sunitinib treatment in mRCC.

Erratum: Improved prognosis for elderly patients with metastatic renal cell carcinoma in the era of targeted therapy.

[This corrects the article DOI: 10.3892/mco.2020.2020.].

[Postoperative Inguinal Hernia after Robot-Assisted Radical Prostatectomy with Prevention Technique Using Spermatic Cord Isolation].

We retrospectivelyevaluated postoperative inguinal hernias (PIHs) after robot-assisted radical prostatectomy(RARP) with a technique for preventing hernias byspermatic cord isolation. Among the RARPs performed from 2016 to 2018, 191 cases were evaluated 12 or more months after surgery. In all the cases, the peritoneum was isolated from the spermatic cord by5 cm or more as a hernia prevention technique during RARP. We compared the background factors between PIH-positive and PIH-negative groups. The PIH-positive group had a significantlylower bodymass index (BMI) than the PIH-negative group (20.6 kg/m2 vs 23.8 kg/m2, p＝0.0079), but there were no significant differences in other background factors. When patients were classified into three groups byBMI, low (＜21.9 kg/m2), intermediate (21.9 to 25.5 kg/m2), and high (＞25.5 kg/m2), the rate of PIH was 8.5% for the low group, 2.1% for the intermediate group, and 0% for the high group. Our findings suggest that incidences of inguinal hernias after the preventive technique of spermatic cord isolation in RARP, and the BMIs tended to be low in the hernia cases.

[ROBOT-ASSISTED RADICAL CYSTECTOMY AT HIROSHIMA CITY ASA HOSPITAL -COMPARISON WITH LAPAROSCOPIC RADICAL CYSTECTOMY].

(Objective) We compared the perioperative parameters of robot-assisted radical cystectomy (RARC) and laparoscopic radical cystectomy (LRC) to evaluate the utility of RARC. (Patients and methods) At Hiroshima City Asa Hospital, 25 patients underwent RARC from July 2018 to May 2020 (R group) and 79 patients underwent LRC from July 2012 to June 2018 (L group). We retrospectively compared the patient characteristics, perioperative outcomes, and pathological outcomes between the R group and the L group. (Results) Regarding the patient characteristics, the R group had significantly more neo-adjuvant chemotherapy than the L group (64.0% vs. 32.9%, P=0.009), but the other characteristics did not differ. Between the R group and the L group, there were no significant differences in the total operating time (R group = 400 minutes vs. L group = 421 minutes), estimated blood loss (R group = 228 ml vs. L group = 318 ml), or pathological outcomes. However, there were significantly less postoperative complications in the R group than in the L group (24.0% vs. 52.6%, P=0.020). (Conclusion) This study showed that there might be benefits to introducing RARC into medical centers that perform LRC.

Prediction of early progression of metastatic renal cell carcinoma treated with first-line tyrosine kinase inhibitor.

BACKGROUND: There are various alternative first-line therapeutic options besides tyrosine kinase inhibitors (TKIs) for metastatic renal cell carcinoma (mRCC). To inform therapeutic decision-making for such patients, this study aimed to identify predictive factors for resistance to TKI. MATERIALS AND METHODS: A total of 239 cases of mRCC patients who received first-line TKI therapy were retrospectively studied. Patients with a radiologic diagnosis of progressive disease within 3 months after initiating therapy were classified as primary refractory cases; the others were classified as non-primary refractory cases. The association between primary refractory cases and age, gender, pathology findings, serum c-reactive protein (CRP) level, metastatic organ status, and 6 parameters defined by the International Metastatic Renal Cell Carcinoma Database Consortium were analyzed. RESULTS: Of 239 cases, 32 (13.3%) received a radiologic diagnosis of progressive disease within 3 months after initiating therapy. The rates of sarcomatoid differentiation, hypercalcemia, a serum CRP level of 0.3 mg/dL or higher, presence of liver metastasis, anemia, and time from diagnosis to treatment interval of less than a year were significantly higher in the primary refractory group. Multivariate analysis showed that sarcomatoid differentiation, hypercalcemia, a serum CRP level of 0.3 mg/dL or higher, and liver metastasis were independently associated with primary refractory disease. A risk-stratified model based upon the number of patients with these factors indicated rates of primary refractory disease of 4.0%, 10.1%, and 45.0% for patients with 0, 1, and 2 or more factors, respectively. CONCLUSIONS: Sarcomatoid differentiation, hypercalcemia, an elevated serum CRP level, and presence of liver metastasis were associated with primary refractory disease in mRCC patients receiving first-line TKI therapy. These results provide clinicians with useful information when selecting a first-line therapeutic option for mRCC patients.

[Outcomes of Laparoscopic Radical Prostatectomies by a Single Surgeon Alternating Operating Position].

The clinical outcome of laparoscopic radical prostatectomy (LRP) was retrospectively investigated taking into consideration the surgeon's position during the procedure. The study cohort included 184 consecutive patients who had undergone LRP performed by a single surgeon from February 2013 to July 2018. During the study period,the surgeon stood alternately on either the left or right side of the patient. The D'Amico risk classification was low,intermediate and high in 26 (14.1%),45 (24.5%) and 113 (61.4%) patients,respectively. Mean surgical duration was 203.5 minutes and mean estimated blood loss was 437.6 ml. Nerve sparing (NS) was implemented in 82 (44. 6%) patients. The mean period of having an indwelling urethral catheter was 5. 0 days. Perioperative Clavien-Dindo degree ≥IIIa complications occurred in three (1.6%) patients. Except for cases with presurgical hormonal treatment,surgical margins were positive in 41 (22.3%) patients,among whom 23 (17.4%) had pT2 disease. The 5-year biochemical recurrence-free survival rate was 81.4%,and 84.8% of patients regained urinary continence at 12 months after surgery. Where the surgeon stood during LRP was not associated with significant differences in any parameter. However,the margin positive rate was higher on the side away from where the surgeon stood than the side closer to the surgeon (70.7% vs 29.3%). In conclusion,the position of the surgeon during LRP does not influence the outcome.

Impact of the systemic immune-inflammation index for the prediction of prognosis and modification of the risk model in patients with metastatic renal cell carcinoma treated with first-line tyrosine kinase inhibitors.

INTRODUCTION: International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria are the most representative risk model for patients with metastatic renal cell carcinoma (mRCC). However, the intermediate-risk group of IMDC criteria is thought to include patients with different prognoses because many of the patients are classified into the intermediate-risk group. In this study, we investigated the impact of systemic immune-inflammation index (SII), which is calculated based on neutrophil count, platelet count, and lymphocyte count, on predicting the prognosis in patients with mRCC, and its usefulness for re-classification of patients with a more sophisticated risk model. METHODS: From January 2008 to January 2018, 179 mRCC patients with a pretreatment and SII were retrospectively investigated. All patients were classified into either a high-SII group or a low-SII group based on the cutoff value of a SII at 730, as reported in previous studies; the overall survival (OS) rates in each group were compared. RESULTS: The median age was 65 years old. Males and females comprised 145 and 34 cases, respectively. The categories of favorable-, intermediate-, and poor-risk groups in the IMDC model were assessed in 39, 102, and 38 cases, respectively. The median observation period was 24 months. The low-SII and high-SII groups consisted of 73 and 106 cases, respectively. The 50% OS in the high-SII group was 21.4 months, which was significantly worse than that in the low-SII group (49.7 months; p<0.0001). Multivariate analysis showed that a high SII was an independent predictive factor for a worse OS. Next, we constructed a modified IMDC risk model that included the SII instead of a neutrophil count and a platelet count. By using this modified IMDC model, all cases were re-classified into four groups of 33, 52, 81, and 13 cases with 50% OS of 88.8, 45.9, 29.4, and 4.8 months, respectively. CONCLUSIONS: The SII is useful for establishing a more sophisticated prognostic model that can stratify mRCC patients into four groups with different prognoses.