Surgical resection of double advanced pancreatic neuroendocrine tumors with multiple renal cell carcinoma associated with von Hippel-Lindau disease.

Von Hippel-Lindau (VHL) disease, an autosomal dominant genetic disorder caused by a germline mutation, is associated with non-functional and slow-growing pancreatic neuroendocrine tumor (PNET) and kidney cancer. We describe the case of a 46 year-old man with a 35 mm mass in the pancreatic head causing stricture of the bile duct and main pancreatic duct, a 55 mm mass in the pancreatic tail causing obstruction of the splenic vein (SV), and multiple masses of > 36 mm on both kidneys. We performed a two-stage resection. First, a total pancreatectomy with superior mesenteric vein (SMV) resection and reconstruction and retroperitoneoscopic right partial nephrectomy (NP) for five lesions was performed, followed by retroperitoneoscopic left partial NP of the five lesions 6 months later. Postoperative histopathological examination revealed NET G2 in the pancreatic head with SMV invasion and somatostatin receptor type 2A (SSTR2A) positivity, NET G2 in the pancreatic tail showed SV invasion and negative SSTR2A, and multiple clear cell renal cell carcinomas (RCC) were also noted. Multiple liver recurrences occurred 22 months after primary surgery. The patient remains alive 41 months after primary surgery. Kidney cancer generally determines VHL prognosis; however, we experienced dual-advanced PNETs with a more defined prognosis than multiple RCC associated with VHL.

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.

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.

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.

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.

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.

[POSTOPERATIVE RECURRENCE OF RENAL CELL CARCINOMA AFTER THE LAPAROSCOPIC PARTIAL NEPHRECTOMY].

(Objectives)The usefulness of partial nephrectomy for renal tumors has been highlighted in various guidelines. Since 2006, we have been actively performing laparoscopic partial nephrectomy for renal tumors. We investigated the postoperative recurrence of renal tumors diagnosed as renal cell carcinoma after laparoscopic partial nephrectomy. (Patients and methods)From August 2006 to March 2020, 320 patients who underwent laparoscopic partial nephrectomy at our hospital and were pathologically diagnosed with renal cancer were included. A retrospective statistical study was conducted to analyze the postoperative recurrence. (Results)Postoperative recurrence was observed in 11 patients (3.4%). The median time to recurrence was 12 months (3-26 months), non-distant metastasis was observed in four cases (1.3%), and distant metastasis was observed in seven cases (2.2%). No statistically significant difference was found in the factors related to recurrence, in this study. (Conclusions)In this study, no statistically significant factors were found, but the higher the clinical stage, the higher the recurrence rate.

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.].

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.

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.

PTEN Is Involved in Sunitinib and Sorafenib Resistance in Renal Cell Carcinoma.

BACKGROUND/AIM: Targeted receptor tyrosine kinase inhibitor (TKI) is a standard treatment in advanced renal cell carcinoma (RCC). However, the role of PTEN in TKI resistance remains poorly understood. We aimed to determine the functional role of PTEN knockout and analyse the predictive significance of PTEN expression for TKI treatment in RCC. MATERIALS AND METHODS: We developed PTEN knockout cells in RCC cell lines using the CRISPR-Cas9 system and analysed the effect of PTEN knockout on spheroid formation and resistance to sunitinib and sorafenib. RESULTS: PTEN knockout promoted spheroid formation and decreased sunitinib/sorafenib sensitivity in RCC cell lines. PTEN immunohistochemistry in 74 metastatic RCCs treated with sunitinib and sorafenib revealed negative PTEN expression in 23% of samples. Kaplan-Meier analysis showed a significant association of negative PTEN expression with poor progression-free survival in metastatic RCC treated with sunitinib and sorafenib (p=0.024) or sunitinib alone (p=0.009). CONCLUSION: PTEN may be a biomarker and therapeutic target in patients with metastatic RCC.

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

The present study investigated the outcomes of targeted therapy for elderly patients with metastatic renal cell carcinoma (mRCC). A total of 277 patients with mRCC who were treated with tyrosine kinase inhibitor as a first-line therapy from January 2008 to May 2018 were retrospectively investigated by reviewing clinicopathological data. Patients 75 years or older were classified into the older-aged group (n=55) while all others were classified into the younger-aged group (n=222). The preoperative clinicopathological characteristics and the overall survival (OS) rate for these two groups were subsequently compared. The median age in the older- and younger-aged groups was 78 and 63 years (P<0.0001), respectively. A total of 7, 42 and 6 cases in the older-aged group and 46, 118 and 58 cases in the younger-aged group were classified into favorable, intermediate, and poor risk groups, respectively. The rate of patients with cardiovascular diseases (29.1%) and malignant diseases other than RCC (20.0%) was significantly higher in the older-aged group compared with the younger-aged group (6.8%; P<0.0001 and 7.2%; P=0.0042, respectively). There was a significant improvement in the OS rate for patients beginning targeted therapy after 2011 compared with those starting therapy prior to 2010. The 50% OS rate in patients starting targeted therapy before 2010 and after 2011 was, respectively, 17.1 and 38.6 months for the older-aged group (P=0.0066), while there was no significant difference for the younger-aged group (P=0.1441; 50% OS; 35.9 vs. 30.5 months). The results of the present study indicated that the prognosis for older patients has improved since the introduction of targeted therapy.

Predictors of poor response to first-generation anti-androgens as criteria for alternate treatments for patients with non-metastatic castration-resistant prostate cancer.

PURPOSE: There are no criteria for administering first- or second-generation anti-androgens (FGA and SGA, respectively) to patients with non-metastatic castration-resistant prostate cancer (nmCRPC). This study aimed to assess the efficacy of alternative FGA therapy in nmCRPC patients and the prognosis of these patients and to identify factors for predicting patients potentially responsive to FGA. METHODS: Data from 63 men with nmCRPC who underwent alternative FGA therapy (bicalutamide, flutamide, or chlormadinone acetate) as first-line therapy after failure of primary androgen-deprivation therapy (PADT) between 2004 and 2017 at Hiroshima University Hospital and affiliated hospitals were retrospectively investigated. The associations of clinicopathological parameters with overall survival (OS) and prostate-specific antigen (PSA) progression-free survival (PFS) of alternative FGA-treated patients were analyzed. RESULTS: Time to CRPC [p = 0.007, hazard ratio (HR) = 4.77], regional lymph node involvement at the diagnosis of CRPC (p = 0.022, HR = 2.42), and PSA-PFS of alternative FGA therapy ≤ 6 months (p = 0.020, HR = 2.39) were identified as prognostic factors using a multivariate analysis. Additionally, Cox proportional hazard models revealed that PSA nadir value > 1 ng/mL during PADT (p = 0.034, HR = 2.40) and time from starting PADT to PSA nadir ≤ 1 year (p = 0.047, HR = 1.85) were predictive factors for worse PSA-PFS in alternative FGA therapy. CONCLUSIONS: Shorter time to CRPC, regional lymph node involvement, PSA nadir during PADT > 1 ng/mL, and time from starting PADT to PSA nadir ≤ 1 year might suggest the potential benefit of immediate commencement of SGA, compared to FGA administration after nmCRPC diagnosis.

[LAPAROSCOPIC RADICAL PROSTATECTOMY OF 926 PATIENTS AT THE HIROSHIMA ENDOUROLOGICAL ASSOCIATION].

(Objective) The aim of this study is to investigate the treatment outcome of laparoscopic radical prostatectomy (LRP). (Patients and methods) The study cohort consisted of 926 hormone-naïve patients with localized prostate cancer who underwent LRP at the Hiroshima Endourological Association from January 2007 to December 2016. (Results) The mean age was 69.4 years, the mean initial PSA was 9.1 ng/ml, and the mean follow-up period was 40.3 months. The D'Amico Risk Classification was Low: 232 cases, Intermediate: 344 cases, and High: 350 cases. Nerve preservation was performed bilaterally for 138 patients and unilaterally for 181 patients. The mean operative time was 181.0 minutes and the mean estimated blood loss was 360.7 ml. As the number of experienced cases increased, the operative time was significantly shorter and the estimated blood loss was significantly decreased. According to Clavien-Dindo classification, the ratio of perioperative complication degree IIIa or above was 4.0% (37 cases). The pathological results were Gleason score (GS) ≤6: 174 cases, GS7: 514 cases, GS ≥8: 232 cases, pT2≥: 704 cases, pT3a: 172 cases, pT3b: 47 cases, pT4: 3 cases, pN0: 917 cases, and pN1: 9 cases. Positive surgical margins were found in 278 cases (30.0%). The biochemical recurrence-free survival rate at 5 years was 78.1%. In multivariate analysis, age (≥70 yrs), initial PSA (≥10 ng/ml), biopsy GS (GS ≥8), cancer positive core ratio at biopsy (≥30%), pT (pT≥3), pathological GS (GS≥8), positive surgical margin and total number of patients in the facility were predictive factors of postoperative biochemical PSA recurrence. Younger age and nerve preservation were found to be predictive factors for the early recovery of urinary continence after surgery, with 88% regaining urinary continence at 12 months after surgery. (Conclusion) This study revealed the clinical outcome and appropriate candidates for LRP in Japanese patients.

Normalization of C-reactive protein levels following cytoreductive nephrectomy in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors is associated with improved overall survival.

INTRODUCTION AND OBJECTIVES: Pretreated C-reactive protein (CRP) has been suggested as one of the most important prognostic factors for metastatic renal cell carcinoma (mRCC). The aim of this study was to investigate the prognostic impact of the change in CRP level before and after cytoreductive nephrectomy (CN) in patients with mRCC treated with tyrosine kinase inhibitor. MATERIALS AND METHODS: The CRP in 60 patients undergoing molecular targeted therapy for mRCC was measured before and after CN. The cutoff value of CRP was determined to be 0.5mg/dl.; thus, all patients were classified into lower CRP groups and higher ones according to their CRP before CN. The higher CRP group was further classified into 2 groups based on the kinetics after CN, "normalized CRP group" and "nonnormalized CRP group," respectively. The overall survival (OS) of these groups was compared. RESULTS: The median of the observation period was 21.6 months. The OS of patients in the lower CRP, normalized CRP, and nonnormalized CRP groups were 28.6, 23.1, and 12.3 months, respectively (nonnormalized CRP group vs. others, P<0.0001). Multivariate analysis revealed that the postoperative CRP level (≥0.5mg/dl) (hazard ratio = 0.218; 95% CI: 0.091-0.522; P = 0.0006) was an independent predictive factor of OS. CONCLUSION: The CRP level after CN can be a predictive factor for OS in patients with mRCC treated with tyrosine kinase inhibitor.

The effect of kinetics of C-reactive protein in the prediction of overall survival in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitor.

INTRODUCTION AND OBJECTIVES: The aim of this study was to investigate the effect of kinetics of C-reactive protein (CRP) in the prediction of overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) treated with a tyrosine kinase inhibitor. MATERIALS AND METHODS: The CRP in 118 cases of molecular-targeted therapy for mRCC was measured before starting the prescription of the first-line targeted agents and at the first time a CT scan was conducted during treatments. All cases were classified into higher-CRP groups and lower ones according to their data at the time of starting treatments. A higher-CRP group was further classified into 2 subgroups based on the kinetics after first-line targeted therapy: "decreased-CRP subgroup" and "nondecreased CRP subgroup." RESULTS: The median of the observation period was 23.4 months. The OS in cases with CRP higher than 0.5mg/dl was significantly worse than those in other cases (P<0.0001). Multivariate analysis revealed that the pretreated CRP (hazard ratio = 2.093; 95% CI: 1.176-3.858; P = 0.0179) was an independent predictive factor of OS. In the higher-CRP group, the OS for the decreased-CRP subgroup (1 year, 85.0%) was significantly better than those for the nondecreased CRP subgroup (1 year, 37.2%, P<0.0001). Multivariate analyses in the higher-CRP group revealed that the decrease in the CRP was an independent predictive factor for OS (hazard ratio = 0.176; 95% CI: 0.064-0.488; P = 0.0008). CONCLUSION: A decrease in CRP as well as pretreatment CRP can be a predictive factor for OS in patients with mRCC treated with a tyrosine kinase inhibitor. Cases with mRCC could be stratified into 3 groups with different prognoses using the pretreated CRP and its changes.

Body mass index as a classifier to predict biochemical recurrence after radical prostatectomy in patients with lower prostate-specific antigen levels.

Prostate cancer, one of the most common malignant tumors among men, is closely associated with obesity and, thus far, several studies have suggested the association between obesity and aggressive pathological characteristics in the United States. However, the effect of obesity on prostate cancer mortality is controversial, and it remains unclear whether obesity contributes to the aggressiveness of prostate cancer in Asian patients. The aim of the present study was to investigate the association between body mass index (BMI) and the clinicopathological characteristics of prostate cancer in 2,003 Japanese patients who underwent radical prostatectomy. There was a significant association between higher BMI and higher Gleason score (GS). The multivariate analysis also revealed that BMI was an independent indicator for GS ≥8 at surgery. Moreover, among patients with lower prostate-specific antigen levels, biochemical recurrence-free survival was significantly worse in those with higher BMI. These results suggest that BMI may be a classifier for predicting adverse pathological findings and biochemical recurrence after radical prostatectomy in Japanese patients.

Reliability of laparoscopic skills assessment on video: 8-year results of the endoscopic surgical skill qualification system in Japan.

BACKGROUND AND PURPOSE: The Japanese Urological Association and Japanese Society of Endourology established a urologic laparoscopic skills qualification system called the Endoscopic Surgical Skill Qualification (ESSQ) System in Urological Laparoscopy in 2004. The reliability of video assessments by referees was evaluated. MATERIALS AND METHODS: Videos of nephrectomies or adrenalectomies performed by the applicants were assessed by two referees selected among a pool of 42 referees. From 2004 to 2011, 1308 urologists applied and 60.2% were qualified after video assessments. The results of skills assessments on 1220 videos that had fixed points by two referees were analyzed statistically. RESULTS: The average number of videos that each referee assessed was 58.1, with a range of 16 to 87. The accordance rate of the results of the video assessment, pass or fail, by the two referees was 68.9%. The scores of the video assessment by each referee averaged 62.7±2.4 (standard deviation) (full score was set at 75 points and ≥60 points was needed to pass). There was a statistically significant difference in the average video assessment score among the referees (P<0.001), and five referees showed significantly higher or lower average scores than the other referees. The percentage qualification of the final decision made by the Referee Committee on the videos originally assessed by each referee showed no significant differences among the 42 referees. The accordance rate of the results from the video assessment by each referee with the final decision by the committee showed a statistically significant positive correlation with the number of videos assessed by each referee (r=0.404, P=0.0080). CONCLUSIONS: The ESSQ system showed moderate reliability for the video assessments by the referees. It was concluded that the video assessments by the referees were fair for all applicants, because the final qualification rates showed no significant differences among the referees.